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Finite
This work consists of over 3500 matches burning in the word 'finite'. I took influences from Martin Creed's large word installations as well as Gustav Metzger's 'auto-destructive' work, in which the destruction of the piece is the art. The word finite, which means 'limited', was intended to reflect the damage to the earth's natural resources and how they are irreplaceable once damaged. The burning process demonstrates how resources are easily destroyed and that many things in life are only temporary.
The Revenant Sisterhood’s primary war fleet is composed of immensely powerful yet irreplaceable battle walkers, discovered amidst the military ruins of the old world. Their desiccated mainframes and ancient radiation-saturated nuclear reactors necessitated the development of the Holy Symbiote, fallen sisters whose partially disembodied spirits could pilot the machines, while withstanding their poisonous emanations… for a time.
The development of the Apostle, the first such machine ever to be manufactured in the modern age, marks a watershed moment in the history of the Sisterhood. A lightweight frame constructed of a composite of demon bone and steel means it can be driven by conventional diesel engines, and therefore conventional pilots. At last, the Matriarch is within reach of a vast machine army.
For the time being, the Apostle has been tasked with escort duty, providing much needed support to long-range battle walker rearmament convoys, but it may yet see a general combat role in the near future.
The Revenant Sisterhood’s primary war fleet is composed of immensely powerful yet irreplaceable battle walkers, discovered amidst the military ruins of the old world. Their desiccated mainframes and ancient radiation-saturated nuclear reactors necessitated the development of the Holy Symbiote, fallen sisters whose partially disembodied spirits could pilot the machines, while withstanding their poisonous emanations… for a time.
The development of the Apostle, the first such machine ever to be manufactured in the modern age, marks a watershed moment in the history of the Sisterhood. A lightweight frame constructed of a composite of demon bone and steel means it can be driven by conventional diesel engines, and therefore conventional pilots. At last, the Matriarch is within reach of a vast machine army.
For the time being, the Apostle has been tasked with escort duty, providing much needed support to long-range battle walker rearmament convoys, but it may yet see a general combat role in the near future.
archaeological resources are fragile & irreplaceable. The Archaeological Resources Protection Act of 1979 7& the Federal Land Policy & Management Act of 1976 protect them for the benefit of all Americans.
Please Don't Erase The
Traces of America's Past
Any person who, without authorization, excavates, removes, damages, or otherwise alters or defaces any historic or prehistoric site, artifact or object of antiquity on the public lands of the United States is subject to arrest & penalty of law.
"Do not let the fire go out, spark by irreplaceable spark in the hopeless swaps of the not quite, the not yet, and the not at all. Do not let the hero in your soul perish in lonely frustration for the life you deserved and have never been able to reach. The world you desire can be won. It exists. It is real. It is possible. It is yours..."
— Ayn Rand
EXPLORED
...a mia nonna...donna insostituibile..instancabile....con le sue mani ha "costruito" cose straordinarie....e tra queste anche la mia vita...
... to my grandmother...irreplaceable woman....tireless....with her own hands has "built" amazing things....and among these my life too ...
Everly favourite all time song
Irreplaceable
Beyoncé
Broadgate City of London.
Everly is Italian from a town called Marche which she said was a really lovely place. She is in London studying Security and we bumped into each other in the weekend emptiness of Broadgate. I took a few portraits then Everly said 'no more that is enough'. As she picked up her bags I did manage to ask her how she was getting on and she told me she had registered with an agency to do some cleaning jobs to supplement her study's but they gave her work quite far away from where she lived so of course incurring transport costs and if she was late she would be charged by the agency! I hope she manages to over come this and complete her study's.
www.flickr.com/groups/100strangers/
© All rights reserved please do not use on any other websites or blogs without my explicit permission.
EmAraTy.. W rAsy Bel sMa maRfoO3..
EmAraTy.. W EsMy bEl Fa5Ar mA6BoO3...
Model: nass fel maseera.. =Pp
Taken by: Me + irreplaceable << not in flickr
Edited by : Me
Location: maseerat AD 2008
αℓℓ яιgнтѕ яєѕєяνє∂ ©
ppl COMMENT dont just view..
plz..(A)
MaLy MtheEl ©Copyright . photostream can not be copy, download, or used in any ways without my permission.
What a place for a sunflare Lola! That's actually as there's a tiny scratch (it occured during Malawi) on the lens, which as far as I'm aware is irreplaceable. It likes creating white spots on most photos, they're just usually not that obvious.
Ha, my expression. I didn't know I was capable of an elegant "loss" expression, usually I just look like I'm in pain. But I don't hate this. I just look sad. Obviously that's the point - I'm Demeter, and my daughter Persephone has just been stolen by the underworld god, Hades. I'm the goddess of seasons and life (hence, flowers). Demeter wore a dark veil to signify mourning (hence, scarf). Yes there's a summer house behind me, but I'll get rid of that some other time.
Now my neighbours think I'm mad, and I smell like lavender. Sweet dreams for me tonight please.
This was fun, and very impromptu. Was supposed to be going shopping but got cancelled (going now instead) so I jumped outside in the COLD and took some photos in the beautiful sun. Hey, sun, I missed you!!!
suggestions for fancy dress outfits for a "goodies vs baddies" party? I'm a bit of a villain girl, if you've got any ideas? Much appreciated!
Mi cara ajajajaj xd ! se supone que era un besito8-).. >.< .. esta cancion me la robo el taty 88 yo se la dije porque me acordaba de el ._. ..
Te juro que no te aguanto más
No te quiero ya ni como amante
Esta vez no ganarás
Te puedes marchar y no vuelvas jamás..
Este cuento al fin se ha acabado
Me verás con otro hombre a mi lado
Ya lo ves traidor voy a sustituirte
Voy a olvidar tu amor… ♪ ♪
More than half of England’s medieval stained glass is held in York Minster’s 128 windows, making the cathedral custodian of some of the most important and irreplaceable art from this period.
In Order to be irreplaceable one must always be Different.
Coco Channel..
The New Collection of Posh Pixels
LeBlanc Gown
Simplicity is the Key Note of all true Elegance
♥ I - Irreplaceable: Không thể thay thế
Giữa bao la c.sống, bạn tìm thấy 1 người phù hợp với mình, điều này đôi khi k dễ dàng chút nào cả. Vì thế, bạn phải biết trân trọng những gì mình đang có, và "I" đôi khi k đơn giản là bạn, mà cho cả "người k thể thay thế" của mình !
♥ L - Love: Yêu thương
Yêu thương là tình cảm cthể hàn gắn mọi nỗi đau trên thế gian này, phải k nhỉ?
Hãy dành yêu thương cho tất cả mọi người để k có nỗi đau nào đến với mình ^^
♥ O - Observe: Quan sát
Nếu dành t.cảm cho 1 ai đó, bạn sẽ để ý quan sát họ ở mọi góc cạnh, để hiểu cả ưu điểm lẫn khuyết điểm của họ.
Yêu 1 người, k chỉ yêu những nét đẹp của họ, mà yêu cả những nét chưa đẹp của họ nữa ! Đó mới thực sự hoàn hảo :)
♥ V - Veracity: Sự thành thật
Thành thật k phải là nói hết tcả những điều bạn snghĩ ! Mà thành thật là k giấu giếm những điều qtrọng.
Bạn có nỗi buồn? Nếu người đó k phải là hình ảnh đầu tiên bạn nhớ đến để sẻ chia thì có lẽ, t.cảm của bạn cần phải xem lại. Bởi ở một góc độ nào đó, t.yêu bắt đầu đc nhen nhóm từ sự đồng cảm và sẻ chia, quan tâm !
♥ E - Enjoy: Tận hưởng
Đừng suy nghĩ quá nhiều !! Nếu 2 người đang yêu, hãy dành cho nhau tcả những gì tuyệt vời nhất. Cùng nhau học tập, vui chơi, làm những công việc có ích. Đừng snghĩ quá dài: "Mai này sẽ thế nào nhỉ?" ...
Hãy cứ làm thật tốt cho hiện tại đã ^^
♥ Y - Yourself: Là chính bạn
Cthể bạn k hoàn hảo và xinh đẹp, nhưng bạn nhớ rằng, bạn là duy nhất trên thế giới này !
Cho dù bạn có anh chị em sinh đôi, họ cũng khác bạn rất nhiều !
Đó là sự quy ước của tạo hóa. Vì thế, hãy cố gắng để hoàn thiện bản thân mình mỗi ngày, đừng bao giờ tự hành hạ hay buông xuôi vì bất cứ điều gì ^^
♥ O - Only: duy nhất:
Bạn có biết tsao mỗi người lại chỉ có 1 trái tim không? Vì đó là nơi dành cho t.yêu đó !
Khi yêu 1 ai đó, bạn làm tất cả cho người đó và trong mắt người đó, cthể cũng chỉ có bạn, nên đừng phụ lòng người yêu mình ^3^
♥ U - Understand: Thấu hiểu
Tsao thấu hiểu lại là cuối cùng nhỉ? Vì sau tcả những điều trên, điều còn lại là bạn có chấp nhận và thấu hiểu tcả để gắn bó cùng người đó hay k.
Hãy làm tcả những điều gì mà bạn cho là cần thiết để t.cảm của mình đc tốt hơn !
I LOVE YOU, all :*
Cry on my shoulder :)) Khi bùn bạn kím ai? Kím Hân nè chứ ai :))
In Order to be irreplaceable one must always be Different.
Coco Channel..
The New Collection of Posh Pixels
LeBlanc Gown
Simplicity is the Key Note of all true Elegance
Finnish soldier and his best friend in the village of Sunku in Karhumäki, August 14, 1942.
Finnhorse was an irreplaceable helper in Finland’s wars. They worked in tough conditions and took the soldiers to places no other vehicle could.
During the wars, tens of thousands of Finnhorses pulled the cannons, delivered food and mail to the front and took the injured and fallen soldiers to safety.
••••••••
Suomalainen sotilas ja hänen paras kaverinsa Sunkun kylässä Karhumäessä, 14.8.1942.
Suomenhevonen oli korvaamaton apulainen Suomen sodissa. Hevoset työskentelivät vaikeissa olosuhteissa ja veivät sotilaita paikkoihin, joihin muut ajoneuvot eivät pystyneet.
Rintamalla palveli Suomen sodissa vuosina 1939–45 kymmeniätuhansia suomenhevosia jotka vetivät tykkejä, kuljettivat ruokaa, ammuksia ja kenttäpostia etulinjoille ja toivat sieltä takaisin kaatuneita ja haavoittuneita sotilaita.
Hevoset oppivat pärjäämään tilanteissa, jossa haavoittunut sotilas ei kyennyt enää toimimaan. Kerrotaan, miten huoltohevonen osasi palata takaisin huoltojoukkojen luo, vaikka ajuri makasi kärryillä verenhukasta tajuttomana.
••••••••
[ sa-kuva | 104053 | Nurmi ]
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
_-----------------------------------------
The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
——————————————————————————
(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
Cappadocia - World Heritage List.
In a spectacular landscape, entirely sculpted by erosion, the Göreme valley and its surroundings contain rock-hewn sanctuaries that provide unique evidence of Byzantine art in the post-Iconoclastic period. Dwellings, troglodyte villages and underground towns – the remains of a traditional human habitat dating back to the 4th century – can also be seen there.
Brief synthesis
Located on the central Anatolia plateau within a volcanic landscape sculpted by erosion to form a succession of mountain ridges, valleys and pinnacles known as “fairy chimneys” or hoodoos, Göreme National Park and the Rock Sites of Cappadocia cover the region between the cities of Nevşehir, Ürgüp and Avanos, the sites of Karain, Karlık, Yeşilöz, Soğanlı and the subterranean cities of Kaymaklı and Derinkuyu. The area is bounded on the south and east by ranges of extinct volcanoes with Erciyes Dağ (3916 m) at one end and Hasan Dağ (3253 m) at the other. The density of its rock-hewn cells, churches, troglodyte villages and subterranean cities within the rock formations make it one of the world's most striking and largest cave-dwelling complexes. Though interesting from a geological and ethnological point of view, the incomparable beauty of the decor of the Christian sanctuaries makes Cappadocia one of the leading examples of the post-iconoclastic Byzantine art period.
It is believed that the first signs of monastic activity in Cappadocia date back to the 4th century at which time small anchorite communities, acting on the teachings of Basileios the Great, Bishop of Kayseri, began inhabiting cells hewn in the rock. In later periods, in order to resist Arab invasions, they began banding together into troglodyte villages or subterranean towns such as Kaymakli or Derinkuyu which served as places of refuge.
Cappadocian monasticism was already well established in the iconoclastic period (725-842) as illustrated by the decoration of many sanctuaries which kept a strict minimum of symbols (most often sculpted or tempera painted crosses). However, after 842 many rupestral churches were dug in Cappadocia and richly decorated with brightly coloured figurative painting. Those in the Göreme Valley include Tokalı Kilise and El Nazar Kilise (10th century), St. Barbara Kilise and Saklı Kilise (11th century) and Elmalı Kilise and Karanlık Kilise (end of the 12th – beginning of the 13th century).
Criterion (i): Owing to their quality and density, the rupestral sanctuaries of Cappadocia constitute a unique artistic achievement offering irreplaceable testimony to the post-iconoclastic Byzantine art period.
Criterion (iii): The rupestral dwellings, villages, convents and churches retain the fossilized image of a province of the Byzantine Empire between the 4th century and the arrival of the Seljuk Turks (1071). Thus, they are the essential vestiges of a civilization which has disappeared.
Criterion (v): Cappadocia is an outstanding example of a traditional human settlement which has become vulnerable under the combined effects of natural erosion and, more recently, tourism.
Criterion (vii): In a spectacular landscape dramatically demonstrating erosional forces, the Göreme Valley and its surroundings provide a globally renowned and accessible display of hoodoo landforms and other erosional features, which are of great beauty, and which interact with the cultural elements of the landscape.
Integrity
Göreme National Park and the Rock Sites of Cappadocia, having been extensively used and modified by man for centuries, is a landscape of harmony combining human interaction and settlement with dramatic natural landforms. There has been some earthquake damage to some of the cones and the pillars, but this is seen as a naturally occurring phenomenon. Overuse by tourists and some vandalism have been reported and some incompatible structures have been introduced.
The erosional processes that formed the distinctive conical rock structures will continue to create new fairy chimneys and rock pillars, however due to the rate of this process, the natural values of the property may still be threatened by unsustainable use. The cultural features, including rock-hewn churches and related cultural structures, mainly at risk of being undermined by erosion and other negative natural processes coupled with mass tourism and development pressures, can never be replaced. threats Some of the churches mentioned by early scholars such as C. Texier, H.G. Rott and Guillaume de Jerphanion are no longer extant.
Authenticity
The property meets the conditions of authenticity as its values and their attributes, including its historical setting, form, design, material and workmanship adequately reflect the cultural and natural values recognized in the inscription criteria.
Given the technical difficulties of building in this region, where it is a matter of hewing out structures within the natural rock, creating architecture by the removal of material rather than by putting it together to form the elements of a building, the underlying morphological structure and the difficulties inherent in the handling of the material inhibited the creative impulses of the builders. This conditioning of human effort by natural conditions persisted almost unchanged through successive periods and civilizations, influencing the cultural attitudes and technical skills of each succeeding generation.
Protection and management requirements
The World Heritage property Göreme National Park and the Rock Sites of Cappadocia is subject to legal protection in accordance with both the Protection of Cultural and Natural Resources Act No. 2863 and the National Parks Act No. 2873. The entire territory between the cities of Nevşehir, Ürgüp and Avanos is designated as a National Park under the Act No. 2873. In addition, natural, archaeological, urban, and mixed archaeological and natural conservation areas, two underground towns, five troglodyte villages, and more than 200 individual rock-hewn churches, some of which contain numerous frescoes, have been entered into the register of immovable monuments and sites according to the Act No. 2863.
Legal protection, management and monitoring of the Göreme National Park and the Rock Sites of Cappadocia fall within the scope of national and regional governmental administrations. The Nevşehir and Kayseri Regional Conservation Councils are responsible for keeping the register of monuments and sites, including carrying out all tasks related to the legal protection of monuments and listed buildings and the approval to carry out any restoration-related works. They also evaluate regional and conservation area plans prepared by the responsible national and/or local (i.e. municipal) authorities.
Studies for revision and updating of the existing land use and conservation plan (Göreme National Park Long-term Development Plan) of 1981 were completed in 2003. The major planning decisions proposed were that natural conservation areas are to be protected as they were declared in 1976. Minor adjustments in the peripheral areas of settlements and spatial developments of towns located in the natural conservation sites including Göreme, Ortahisar, Çavuşin, Ürgüp and Mustafapaşa will be strictly controlled. In other words, the Plan proposes to confine the physical growth of these towns to recently established zones. Hotel developments will take into account the set limits for room capacities. Furthermore, the plan also suggested that local authorities should be advised to review land use decisions for areas that have been reserved for tourism developments in the town plans.
Preparation of conservation area plans for the urban and/or mixed urban-archaeological conservation sites within the historic sections of Göreme are in place and provide zoning criteria and the rules and guidelines to be used in the maintenance and restoration of listed buildings and other buildings which are not registered, but which are located within the historic zones. Similar planning studies for the towns of Ortahisar and Uçhisar are in place. Once finalised, a conservation area plan for the urban conservation area in Ürgüp will be in place. All relevant plans are kept up to date on a continuing basis.
Appropriate facilities aimed at improving the understanding of the World Heritage property have been completed for the subterranean towns of Kaymaklı and Derinkuyu, and are required for Göreme and Paşabağı.
Monuments in danger due to erosion, including the El Nazar, Elmalı, and Meryemana (Virgin Mary) churches, have been listed as monuments requiring priority action. Specific measures for their protection, restoration and maintenance are required at the site level.
While conservation plans and protection measures are in place for individual sites, it is recognised by the principal parties responsible for site management that an integrated Regional Plan for the Cappadocia Cultural and Tourism Conservation and Development Area is required to protect the World Heritage values of the property. Adequate financial, political and technical support is also required to secure the management of the property.
www.nationalgeographic.com/travel/world-heritage/cappadocia/
Memorial plaque (below the "05" sign to the right of the Giant Gate)
Text:
05 was the secret symbol of the
Austrian resistance against
the National Socialist regime of terror 1938-1945.
This memorial was erected in memory of the murdered
Resistance fighters of the Austrian Resistance Movement
under President Prof. Norbert Macheiner in Oct. 2000.
AEIOU In All Seriousness is Austria
Irreplaceable.
Founder: Austrian resistance movement
The commemorative plaque was unveiled on the occasion of an Austria-Demonstration carried out by the Austrian Resistance Movement on October 5, 2000, after a memorial mass celebrated by military general prelate Rudolf Schütz for the victims of the Nazi regime and the awarding of the Golden Honarary Needle to Otto Habsburg-Lorraine.
The symbol "05" comes from the medical student Jörg Unterreiner and was painted from the early autumn of 1944 on the walls of houses and churches by the resistance group of the same name, which understood itself as a reservoir of pro-Austrian forces. Previously or at the same time of this symbol, Austrian resistance groups such as the Austrian Freedom Movement, Friedrich Wildgans ("Berghofbauer" - Mountain Farm Peasant) or the Slovenian partisans in Carinthia used both their partisan symbols and other signs of resistance.
The vocabulary series AEIOU is interpreted in the Austrian lexicon as follows: "It is Austria's purpose to rule the world", "Austria will be eternal" and "All soil is subject to Austria". (Österreich Lexikon, Volume 1, page 9)
See also: Commemoration and Admonishing in Vienna 1934-1945, p. 68.
Gedenktafel (unter dem "05"-Zeichen rechts vom Riesentor)
Text:
05 war das Geheimsymbol des
österr. Widerstands gegen
das nationalsozialistische Schreckensregime 1938–1945.
Dieses Mahnmal wurde zum Andenken an die ermordeten
Widerstandskämpfer der öst. Widerstandsbewegung
unter Präs. Prof. Norbert Macheiner im Okt. 2000 errichtet.
AEIOU Allen Ernstes ist Österreich
unersetzlich.
Stifter: Österreichische Widerstandsbewegung
Die Enthüllung der Gedenktafel erfolgte anlässlich einer von der Österreichischen Widerstandsbewegung durchgeführten Österreich-Kundgebung am 5. Oktober 2000 nach einer von Militärgeneralvikar Prälat Rudolf Schütz zelebrierten Gedenkmesse für die Opfer des Nazi-Regimes und der Verleihung der Goldenen Ehrennadel der Österreichischen Widerstandsbewegung an Otto Habsburg-Lothringen.
Das Symbol "05" stammt von dem Medizinstudenten Jörg Unterreiner und wurde ab dem Frühherbst 1944 von der sich als Sammelbecken proösterreichischer Kräfte verstehenden Widerstandsgruppe gleichen Namens an Haus- und Kirchenwände gemalt. Zuvor bzw. neben diesem Symbol verwendeten österreichische Widerstandsgruppen wie etwa die Österreichische Freiheitsbewegung, Friedrich Wildgans ("Berghofbauer") oder die slowenischen Partisanen in Kärnten sowohl ihre Partisanensymbole als auch andere Zeichen des Widerstandes.
Die Vokabelreihe AEIOU wird im Österreich-Lexikon folgendermaßen gedeutet: "Es ist Österreichs Bestimmung, die Welt zu beherrschen", " Österreich wird ewig sein" und "Alles Erdreich ist Österreich untertan". (Österreich Lexikon, Band 1, Seite 9.)
Siehe dazu auch: Gedenken und Mahnen in Wien 1934–1945, S. 68.
These small dunes were formed by north winds pushing sands off the Cadiz Dry Lake. The pristine nature of the dunes and the beautiful spring display of unique dune plants have made the area a favorite for photographers.
On February 12, 2016, President Obama signed a proclamation declaring the Mojave Trails National Monument east of Los Angeles in Southern California.
Mojave Trails National Monument: Spanning 1.6 million acres, more than 350,000 acres of previously congressionally-designated Wilderness, the Mojave Trails National Monument is comprised of a stunning mosaic of rugged mountain ranges, ancient lava flows, and spectacular sand dunes. The monument will protect irreplaceable historic resources including ancient Native American trading routes, World War II-era training camps, and the longest remaining undeveloped stretch of Route 66. Additionally, the area has been a focus of study and research for decades, including geological research and ecological studies on the effects of climate change and land management practices on ecological communities and wildlife.
Photo by Bob Wick, BLM.
Amboy Crater is an iconic landscape feature that guides travelers along Route 66. The site provides easy access (low-clearance 2wd) to visitors wanting to experience Mojave Trails National Monument.
Mojave Trails National Monument just east of Los Angeles, California spans 1.6 million acres and includes rugged mountain ranges, ancient lava flows and fossil beds, and spectacular sand dunes. The Monument also contains irreplaceable historical resources, such as the longest-remaining undeveloped stretch of the iconic Route 66 and World War II training camps.
Photo by Bob Wick, BLM.
Fiberglass figures seen at Professor Cline's Haunted Monster Museum & Dark Maze, Natural Bridge, Virginia. June 9, 2011
April of 2021, fire would consume the entire property.
Located off Route 130 on Bell Tower Road where BTR dead ends in the woods
Burning roadside: Can Mark Cline rise again from the ashes?
By Hawes Spencer | hawesinsky@gmail.com
Published online 6:07am Wednesday May 23rd, 2012
and in print issue #1121 dated Thursday May 24th, 2012
A mid-April blaze demolished the Victorian-era mansion that served as the Haunted Monster Museum as well as the centerpiece of a bizzaro place called Dinosaur World where dinos would gobble Union soldiers and where brave visitors could also hunt Bigfoot with a "redneck." But the fire means no attractions this summer from Mark "Professor" Cline.
"We're gonna take a break this year," says Cline. "I just need more time to regroup."
Although the fiberglass dinos in the woods outside were saved, the Monster Museum was incinerated. The mechanical rats, the "Elvis-stein" monster, and the mighty fiberglass python that seemed to slither in and out of the second-story gable windows all went up in flames late on the afternoon of April 16.
During a next-day visit, the ruins are still smoldering when a State Police investigator shoos a reporter from the scene.
"This is Natural Bridge property," barks the officer, as Cline ushers the visitor away from the charred house.
"He was my dragon," laughs Cline, recalling the era when the future officer was a teenager piloting not a Crown Victoria but a lawn tractor and sporting a character costume at Cline's last attraction, the Enchanted Castle. In a still-unsolved 2001 fire, a blaze whose investigation (or lack thereof, as he alleges) still makes Cline bristle with anger, the Enchanted Castle went up in flames.
"I'd much rather have Barney Fife and Inspector Clousseau out here," says Cline, recalling how State Police investigators conducted interviews hinting that Cline himself had torched the Enchanted Castle, despite the fact that the Castle was uninsured, and that he lost his office, his studio, and all the irreplaceable 8-millimeter films he made as a boy.
"We've done a pile of work on that case," says George "Stick" Austin, the State Police captain overseeing that investigation, noting that it's standard procedure to interview owners. "It is still considered an active investigation."
As for the recent fire, it was an otherwise uneventful spring afternoon when Cline says he was on the grounds of his studio, where– with a small crew– he manufactures fiberglass figures for America's roadside playgrounds.
"I got a call at about 5:45 from the assistant general manager of Natural Bridge," says Cline. "I dropped everything and ran outside."
Cline pauses, looking mournfully down the highway in the direction of the smoldering ruins.
"I looked up and saw a plume of thick black smoke," he says, "and I knew immediately it was gone."
By the time Cline could speed the three miles south on Lee Highway, what may have started as a minor blaze on a stage at one end of the structure had become an engulfing inferno. Cline snapped a few photographs as the mansion cooked.
At the time of a reporter's visit 24 hours later, all that's left are a trio of chimneys and the front wall, executed in a rusticated gray limestone.
To 64-year-old Kilmarnock resident Ann Gill, whose grandparents owned and operated the structure as a hotel/antique shop called "Stonewall Lodge," it's a crushing blow.
"It was a romantic old home," says Gill. "My mother was married there."
In the years after Gill's family sold the structure in the 1950s, the Natural Bridge company eventually let the place go to seed, and by the 1980s the expansive front lawn had reverted to forest.
Cline says the abandoned house seemed creepy when, a decade ago, he approached the owner, Natural Bridge LLC, with his plan to haunt it. In 2002, he unveiled his Haunted Monster Museum there. Two years later, as an April Fool's prank, he built a full-size replica of Stonehenge called Foamhenge about a mile away.
The past two decades have been a tough time on traditional road-trip destinations. While Natural Bridge keeps attendance figures under wraps, educational places like Monticello and Colonial Williamsburg reveal numbers that have fallen from their peaks in the pre-Internet, pre-water-park era.
The venerable Homestead Resort just announced plans to put in a water park. Massanutten installed its water park in 2005.
As some may recall, there was a proposal in Charlottesville 20 years ago to give land to a steam train operator. But that was at least five hotels ago, before the Downtown Mall and myriad wineries erupted with enough critical mass to fill all the new lodgings.
Despite having what's been billed as the Seventh Wonder of the natural world, Natural Bridge has had no such luck. The town's newest hotel appears at least 50 years old. A pair of zoos, a cave, a wax museum, an Indian village, and a new indoor butterfly garden helped draw families off the Interstate, but it was Cline's humor/horror compound that drew national attention from roadside enthusiasts.
"It was a nice addition to our attractions and particularly popular with kids," says Natural Bridge general manager Debbie Land. "It's a total loss as they say in the insurance world."
It's a great loss to Kay Lera. A retiree from the San Francisco Bay Area who for nine years ran a B&B in her new hometown of Lexington, Lera notes how one man can make a difference.
"Natural Bridge has the beauty of the bridge and the caverns," says Lera, "but having some wacky humor incorporated into the scenario does make it a family destination."
So strong is the pull of Professor Cline that when an unassuming adult walks into the Taubman Museum of Art in Roanoke to ask what the Museum has to offer, the first words out of the front desk lady's mouth are these: "Well, Professor Cline is gone…"
We didn't even ask about Professor Cline, whose exhibition there had closed a couple of weeks earlier. But when a man hangs a fiberglass King Kong on the side of your museum and breaks attendance records with such twisted figures as the "Franken-chicken," people take notice.
Like the rest of us, Cline says he's now trying to face the prospect of a summer without his Monster Museum. He's seen an uptick in contract work, like the 13 men's room sinks he recently built for the Broadway revival of How to Succeed in Business without Really Trying.
A couple of reality show producers have made inquiries about following him around.
Cline veers between "pissed off" anger at an unknown arsonist and the peace of knowing that nobody was killed or injured in the fire.
"We made a lot of magic there," says Cline, mulling the impermanence of his creations. "Even one day the great Pyramids of Egypt will be just dust in the wind. This might just be one of those messages from the universe saying it's time to move on."
Photograph (C) copyright 2009 Ivan Safyan Abrams. All rights reserved.
This irreplaceable artifact was dissected decades ago to provide a visual example of the manner in which a steam locomotive operates. The destruction wasn't performed by the current Steamtown management, so it's unfair to blame any individuals currently involved with the Site.
The display is attractive, and informative. But it is a woeful example of disregard for history--and it is that disregard that remains a problem at Steamtown.
Perhaps the root cause of Steamtown's sorry condition is lack of funding. It's a shame to have such a beautiful physical plant, clearly intended to house massive exhibits of preserved and restored locomotives, utilized primarily for hackneyed wall displays and charts.
In the meantime, Steamtown's collection of steam locomotives deteriorates at an ever faster rate outside of the buildings, exposed to the harsh elements of the northeast United States' weather, until they will one day be gone.
Beggarwood Park which is a public park which consists of open chalk grassland surrounded by a belt of mature ancient woodland to the north and eastern boundaries, part of which can be seen on the other side of the park. Before the housing development this was a arable field belonging to either Hatch Warren Farm or Kennel Farm.
A ancient woodland that fringes the park can only be called ancient if the site has been continually wooded since 1600. These areas are irreplaceable and as a result the woodland has been designated as a 'Site of Importance for Nature Conservation' (SINC). The dominant trees found within this woodland are beech (Fagus sylvatica), oak (Quercus robur) and ash (Fraxinus excelsior), with an understory of hazel (Corylus avellana), dogwood (Cornus sanguinea) and spindle (Euonymus europaea).
Evidence of the woodland's ancient origin is indicated by the wildflowers which can be seen growing on the woodland floor in spring. These include sweet woodruff (Galium odoratum), sanicle (Sanicula europaea), and wood anemone (Anemone nemerosa).
Bats use the woodland for roosting, foraging and feeding, on addition to a number of birds. The greater spotted woodpecker (Dendrocopus major) can be heard 'drumming' on the trees and nuthatches (Sitta europaea) can be seen scurrying down tree headfirst. Other birds that visit here include chaffinch (Fringilla coelebs), great tit (Parus major) and tawny owl (Strix aluco).
The park lays within the area of Hatch Warren which is a district and ward of Basingstoke in Hampshire, west of the town centre. Neighbouring housing estates include Kempshott and Brighton Hill.
It is primarily served by Brighton Hill Community College (a secondary school) and two junior schools, St Mark's and Hatch Warren.
It lies within the Hatch Warren & Beggarwood ward of Basingstoke and Deane Borough Council.
Hatch Warren shares a Newsletter, the Rabbiter, with Beggarwood and Kempshott Park, and has a small retail park, which includes a supermarket and a petrol station. It also has one pub which is named 'The Portsmouth Arms.' The Pub was due to open in 1996, but was destroyed by arson. It did however open a year later.
Hatch Warren occupies part of the farm which was the home and head office of Rex Paterson, the noted agriculturalist, when it was part of the estate of the Earls of Portsmouth.
Beneath here what is now the Hatch Warren estate lie the hidden remains of prehistoric and medieval villages. Excavation of those parts of the settlements which were to be destroyed by housing development was undertaken by Wessex Archaeology, in stages between 1984 and 1987.
In the Iron Age (3rd - 1st centuries BC), a small settlement was established. First there was an enclosure surrounded by a shallow ditch. This may have been for keeping livestock as no traces of any buildings were found. If there were any houses these must have been situated outside the area which was excavated.
In the 1st century BC a number of ditched enclosures contained the remains of buildings and pits grouped in different areas. Most of the buildings were small and rectangular with just four upright posts set into the ground, one at each corner. These are a familiar find on archaeological sites of this date and are generally thought to have been used for storing grain. Again, no actual houses were found but they must have been close-by as broken cooking pots, tools and small personal items were found. The little farming community seems to have continued to live here until sometime late in the 1st century AD, after the Roman Conquest of AD43, when for unknown reasons the site was abandoned.
The remains of the medieval settlement - possibly those of the lost Village of "Hatch" - included a small church built in the 11th-12th century which was surrounded by a wooden fence. At least six timber square and rectangular houses stood nearby. In the 12th - 14th centuries the graveyard was surrounded by two enclosure ditches. At least 240 graves occurred in the graveyard with several more burials inside the Church. One of these graves contained a pewter chalice and paten - religious items which indicate that this was the burial of a priest.
The small village served by the church and graveyard grew gradually between the 11th and 14th centuries. It included timber houses with tiled roofs, some surrounded by fences, with pits and possibly hearths, and at least one well and a bread oven.
The village economy was based on the keeping of cattle and sheep and the cultivation of wheat, barley, oats and rye. Dogs, cats, geese and horses were also kept and birds such as ducks, partridge and pigeons were tasty additions to the diet. Burnt seeds of raspberry, blackberry, sloe and bullace or damson were found, as well as burnt hazelnuts and catkins which show that woodland fruits and nuts were collected and eaten. Of great interest is the presence of the remains of red and roe deer and of sparrowhawk which suggests some serious hunting in the forest.
This apparently peaceful little village seems to have prospered in the 14th century but although the churchyard ditch was given a good spring clean sometime in the later 15th century, the area covered by the settlement seems to have been reduced and some houses were apparently pulled down. By the end of the 15th century the church had been demolished and extensive areas of building rubble were spread across the graveyard. The village was abandoned, and its name and position were lost until the excavations of the 1980s.
en.wikipedia.org/wiki/Hatch_Warren
Hovenweep Castle, Hovenweep National Monument
A fellow traveler’s admiring eyes shared a sentiment of awe, excitement, and satisfaction, something truly worthwhile and irreplaceable.
KOHAKU and SUOU, two of the three x 1 year-old Snow Leopard cub brothers we are blessed & privileged to have at Tama Zoo in Tokyo. Each one has his own distinctive characteristics and personality. Lovely aren't they, and irreplaceable.
Canon EOS 1D Mk111, EF 300mm f/2.8L IS @ 800 ISO (through wire).
Weed Wacker kicked a rock through my side window. Landscaper will pay for repairs.
Apparently, the glass is irreplaceable. Dealer doesn't have it. I will need to try a wrecking yard.
A diverse delegation of Christian leaders are today delivering an open letter signed by more than 800 Australians calling on Prime Minister Tony Abbott to rethink the government's rejection of the gift of solar panels for Kirribilli House.
"Experts have assured us there is really no practical reason to reject the gift of solar panels for Kirribilli House," said Jody Lightfoot, climate justice campaigner at Common Grace.
"We understand the important heritage value of Kirribilli House so we had a chat to Sydney Lord Mayor Clover Moore who told us the City of Sydney has already installed 5,500 solar panels on nearly 30 buildings including ones with irreplaceable heritage value such as Sydney Town Hall,” said Mr Lightfoot.
The letter rejecting the solar panels came via Michael McCormack, Member for Riverina, in his capacity as the parliamentary secretary to the finance minister.
“The rejection of our gift of solar panels for Kirribilli House is symbolic of the government’s failure to invest in renewables, but we’re here to provide the Prime Minister with an opportunity to choose a brighter future for all Australians and to back the 9 in 10 Australians who want a strong Renewable Energy Target," said Mr Lightfoot.
"We know that climate change means more frequent and intense extreme weather events hitting the world's poorest people the hardest. We only need to look to our Pacific Island neighbours to see the devastating cost of climate change. We could be leading the world in taking action on climate change and as Christians we urge Prime Minister Abbott not to reject the sun's grace," said Jarrod McKenna, National Director of Common Grace.
The gift of twelve solar panels was crowdfunded over four days in December by Common Grace, a movement of Christians who are passionate about Jesus and justice. The Solar Council (the peak body for the solar industry in Australia) offered to install the crowdfunded solar panels for Kirribilli House at no cost.
“Trying something new can feel daunting, but we encourage Prime Minister Abbott to look to the Vatican where in 2008 Pope Benedict accepted a gift of 2700 solar panels to provide clean energy to the Holy See," said Sister Jan Barnett of the Sisters of Saint Joseph.
“More than one hundred Australians pitched in to buy the gift of solar for Kirribilli House and now hundreds more are urging the Prime Minister to accept our gift. The solar panels are a gift for the nation, from the nation, to demonstrate public support for a clean energy future,” said Byron Smith, Assistant Minister, St George's Anglican Church.
“If the City of Sydney can install solar panels on the Sydney Town Hall just across the harbour and Pope Benedict could accept a gift of solar panels for the Vatican, we believe Prime Minister Abbott has no excuses for not accepting our free gift for his Sydney residence," said Mr Smith.
“If the Prime Minister accepts the gift of solar for Kirribilli House he’ll be in good company with 1 in 5 Australian households already using solar,” he said.
The open letter encouraging the Prime Minister to accept the solar gift (signed by more than 800 Australians in the last five days) is below.
Christian leaders delivering the open letter today: Sister Jan Barnett, Sisters of Saint Joseph; Rev. Dr Michael Frost, Founder of Small Boat Big Sea; Byron Smith, Assistant Minister, St George's Anglican Church; Rev. John Buchanan, Minister, St Peter's Presbyterian Church; Rev. David Gore, Uniting Church Minister; Weis Shiuringa, Member, Quakers; Jacqui Remond, Director, Catholic Earthcare Australia; Jody Lightfoot, Climate Justice Campaigner, Common Grace.
THE OPEN LETTER:
Dear Prime Minister Abbott,
We are disappointed that the Government has rejected the gift of solar panels for Kirribilli House that was crowd funded last Christmas by 142 Christians. We had hoped you would accept them as a great first step to get Australia moving towards a strong Renewable Energy Target.
We understand that the reasons for declining the gift are Kirribilli House’s heritage listing, ongoing costs of cleaning and maintenance, and security concerns. So we did some research and found many people in your home state and abroad have overcome these challenges.
Sydney Lord Mayor Clover Moore informed us that the City of Sydney has already installed 5,500 solar panels on nearly 30 buildings including ones with irreplaceable heritage value such as Sydney Town Hall. We discovered Australia’s own actress, Cate Blanchett, installed 1,906 solar panels on Sydney Theatre Company heritage building. I’m sure she’d be willing to give some pointers if you gave her a call?
On cleaning concerns, John Grimes, CEO of the peak body of the solar industry in Australia (Australian Solar Council), informed us that solar panels do not require ongoing cleaning or yearly maintenance - they are cleaned by the rain. Some utilities require a check of the inverter, but this can be done on the ground every five years.
Looking abroad, did you know that President Carter managed to get solar panels installed on the White House way back in 1979? And Pope Benedict negotiated the same kinds of hurdles when he accepted a gift of 2700 solar panels providing clean energy to the Vatican in 2008.
Prime Minister, we believe that a man in your position can overcome challenges like heritage listings and cleaning concerns and choose a brighter future for all Australians. We therefore urge you to implement a strong Renewable Energy Target and accept the gift of solar panels for Kirribilli House, as a powerful signal to the world that Australia’s renewables industry is officially open for business.
Yours sincerely,
Australian Christians and friends
Open letter available online: www.commongrace.org.au/acceptthegift
(Source: www.halo-energy.com ) The German Interior Ministry pressured Sorbian representatives and media to wipe out any memory and public record of this Lusatian Sorb political
statement for self-determination. Lusatia briefing at Foreign Press Association, London May 2002 (Jan Nuk, Domowina Chairman, left / Tomaš
Kappa, Ralph Th. Kappler centre)
Treasure hunt in Sorbian Lusatia
This is a report on Germany’s secret scandal, its treatment of the Sorbian people. They are allowed to perform their folk-dances for German crowds.
Yet, despite their minority rights and despite Lusatia’s abundant mineral riches, the German authorities continue to close down Sorbian schools and kindergartens. As Germany’s State television station MDR revealed recently, irreplaceable landscapes and many Sorb villages have been and continue to be destroyed on the basis of a Nazi law. The Sorbs are the smallest Slavonic nation and a national minority within Germany living in a region called Lusatia. They cultivated Lusatia and have been living there for over 1600 years, always under German pressure to give up their own Slavonic culture.
This Nazi law which was never eliminated, has made it possible to confiscate privately owned houses and commercial properties in Lusatia on a huge scale up to the present day. The original purpose of the law was to feed Hitler’s war machine with the brown-coal of Lusatia. The present German government has allowed the Swedish State energy trust, Vattenfall, to use it to destroy an area in Lusatia the size of Luxemburg.
Sorbs, also known as Wends in their American and Australian exile enclaves, feel uneasy about this assault. In the past, German oppression was always linked to campaigns against their mother tongue. The Sorbian language and culture have managed to survive for more than 16 centuries. Lusatia, or Luzica, as this water-rich country is affectionately called by its First Nation, is one of the most ancient cultivated regions of Europe. Lusatia is blessed with the largest gold, copper and rare earth resources in Germany.
A quarter of our entire nation has been forced to leave our homelands by the mining lobby. We Sorbs are being forced over the cliff, warned Jan Nuk, chairman of the Sorbian umbrella organisation, Domowina, through the Foreign Press Association in London. Shortly afterwards, the gates of Buckingham Palace opened for Sorbian representatives. Sorbs brought the first foreign gift to London during the Golden Jubilee of Queen Elizabeth II. Sorbs have not campaigned in the British capital since the end of WW II. In 1946 they tried, in vain, to lobby in London for Lusatia to join with Czechoslovakia. Up to this day Lusatia is located in the federal states of Brandenburg and Saxony. Despite its natural riches it is continually denigrated as a supposedly undeveloped region by the coal-mining lobby. However the region suffers mainly from a lack of courageous policies. Even twenty years after the collapse of the communist regime, Sorbs have no legitimate democratic representation of their own.
136 obliterated villages
Werner Domain and his wife were the last inhabitants of the Sorbian village of Horno. The seventy year old, retired couple tried to withstand the ongoing intimidation of mining operators. They managed to plant a linden tree in front of their house while giant coal excavators approached amidst deafening noise and clouds of dust. By then, Horno was already deserted and destroyed as if by war. 136 villages disappeared in Lusatian lignite coal craters, right in the heart of Germany. Germany, the self-proclaimed green technology and eco-champion! These brutal actions accelerated the dissolution of the Sorbian people. On the Internet site www.verschwundene-orte.de one can find the melodious names of destroyed Sorbian villages such as Publik, Bukovina, Horno, Barak, Rovno or Lacoma. Horno was destroyed by the Swedish state-owned energy company Vattenfall, although there was no exploitable coal under this village. Vattenfall took over almost the entire East German energy infrastructure during the fall of communism. This was no coincidence, since some of the most prominent East German politicians made a swift career under these lobbying wings. Sweden was also one of the main western trade partners and technology suppliers to the East German communist regime. Today, Vattenfall sponsors Sorbian communications and education infrastructures, which undermines Sorbian self-representation. The Lusatian mining company Laubag announced euphemistically, that they had “appropriated” more than 750 square kilometres of land. What they actually did through this massive land excavation was to destroy an area the size of the City State Hamburg. Prof. Joachim Katzur, head of the Institute for Mining Redevelopment, goes even further in a ZEIT interview: "Actually, the Lusatian mining operators have affected four times as much land, if we also count the land where the flow of below ground water is disturbed.
Thus over 3000 square kilometres of fertile urban Lusatian land were sacrificed to relentless coal mining. 3000 square kilometres of affected land is more than the size of Luxembourg. The size of Lusatia as a whole is comparable to the size of the EU country Belgium. In Germany thousands of square kilometres of fertile land has disappeared in open cast lignite mining craters. This man-made intervention into nature is the biggest transformation of the earth's surface since the last ice age.
Saved these four Dodges for 40 years, hoping to someday restore them. Those wrap-around windshields are irreplaceable. Some worthless punks had "fun"
Joseph Kearns as George Wilson (Mr. Wilson) on Dennis the Menace from 1959 to 1962
Gale Gordon as John Wilson (Mr. Wilson) on Dennis the Menace from 1962 to 1963
Gale Gordon did a nice job replacing the irreplaceable Joseph Kearns. Mr Kearns passed away from a cerebral hemorrhage in 1962. Kearns was replaced in the cast by Gale Gordon, who played George Wilson's brother John.
Gale Gordon went on to bigger success as Mr. Mooney on I Love Lucy.