amorphica.com/networked.html

Group 4_

Aaron Onchi, Betty Sanchez, Roberto Gutierrez, Frank Durán , Belén Olaya García

Networked Fabrication for Urban Provocations.

Shifting Paradigms from Mass Production to Mass Customization

Computational architecture and design course

Conventional construction methods all depart from the basic premises of mass production: standardization, modulation and a production line. What these systems developed during the last two centuries fail to take into account are the evolutionary leaps and bounds the manufacturing industry has taken over the last decades. With the introduction of CNC technologies and rapid prototyping machines have altered the paradigms of fabrication forever. It is due to these new tools that it is now possible to create (n) amount of completely unique and different pieces with the same amount of energy and material that is required to create (n) identical pieces. The possibilities for implementation of new forms, textures, materials and languages are infinite due to the versatility that these new tools offer a growing network of architects, designers, fabricators that are integrating them into their professional practices to generate unique and precise objects that respond to countless data and real-life conditions.

Instructors:

Monika Wittig [ LaN, IaaC ]

Shane Salisbury [ LaN, IaaC ]

Filippo Moroni [ SOLIDO, Politecnico di Milano ]

MS Josh Updyke [ Advanced Manufacturing Institute, KSU, Protei ]

Aaron Gutiérrez Cortes [ Amorphica ]

§ Eventually, after a long sequence of successive impressions that incessantly compassed into our experiences, the journey is terminated to a dissolution of serenity when we stand confronting the frontage of central sikhara • The incremental aspect in the anthropometrical scale of sikhara is inverse to the decremental determination in the sensational space of our Self • When our expectation was aroused in each step of experiences, we finally can substantiate the salient characteristics of this destination • The architect articulated the modulation of scale and space as cogent mean to stimulate our delectation while enforcing us simultaneously to be aware of our deterioration before affirming them into emancipation at end •

§ The galleries that conjoin to each cardinal axis of the central sikhara project our eyes to elevate from the horizontal line to the finial • The massive form of God proposes incisively an effect to our senses and elicits an emotion to its plastic form that wakes a profound reverberation in us • The ever-diminishing tiers of the curvilinear sikhara assist our eyes to comprehend the finial, and thereby the infinite atmosphere above the sky and the Universe • The formal diminution of its superstructure, by the dimensional depth of its perspective in compliant with the inventive space of the vaporous cloud that oscillates about the finial, reveals the ingenious articulation of the architect in maturating our contemplation with deepest relaxation •

§ Angkor Vat is not an autotelic architecture • The manifestation of the Universe, the objective world of reality, the analogy of God to the subjective realm of Truth in Self, all were simply existed here • A brief tenancy of ego (ahamkara) in the world of human egocentrism in the past, the present, and the future is a mere delusion; only when we can deliberate ourselves from ignorance • Time is a reflexive force of space which contains in all animate beings with ignorance • Only quintessence of our Self-Realisation will terminate time and space of here and there everlastingly •

Crown XLS1000 DriveCore Series Power Amp Description:

Crown's XLS1000 power amplifier is a premiere portable PA system with unmatched performance, technology, and affordability. It includes multiple inputs so you can plug in anything and play anywhere, along with several system setup configurations. This high-performance Crown power amp provides enormous power and flexibility thanks to the integrated DriveCore Technology, PureBand Crossover System and Peakx limiters. Weighing less than 12 pounds, The Crown XLS1000 power amp is much easier to set up and move from show to show.

A Power Amp with Integrated DriveCore Technology Class D amplifiers are notable for extraordinarily high efficiency and being well suited for driving difficult reactive loads such as subwoofers. However, their performance can suffer impaired performance on marginal and unstable AC line supplies. To overcome this obstacle, Crown engineers developed DriveCore Technology—a proprietary hybrid analog-digital integrated circuit (IC) developed with Texas Instruments that drives the "front end" of the Class D output stage. Over 60 years of Crown's design knowledge and experience went into the development of this technology resulting in truly remarkable benefits. The DriveCore Technology incorporated in the Crown XLS1000 power amp provides an extremely wide tolerance with regards to sagging or "dirty" AC line conditions, providing consistent performance without affecting audio quality. This means the Crown power amp will not compromise your performance by fluctuating generator power, or overload from lighting rigs, backline gear, etc.

In addition, DriveCore Technology's patented feedback and PWM modulation circuits enable fast recovery on peak transients, accurate reproduction of low-level detail, and precise tracking of low-frequencies at high power levels for maximum subwoofer output.

Advanced Switched-Mode Power Supply

The advanced power supply in the Crown power amp is highly efficient and optimized for maximum power transfer from the AC line through the Class D output stage to the loudspeakers. A benefit to this is substantial weight reduction when compared to older 60Hz transformer-based power supplies.

PureBand Crossover System

The PureBand Crossover System in the XLS Series adds an enormous amount of flexibility and performance to any system. With this system, the crossover frequency is completely variable allowing the choice of any crossover point between 50Hz and 3kHz on 1/12 octave centers. The use of 4th order Linkwitz-Riley filters provides steep slopes for a seamless transition between high and low drivers. And with four crossover modes to choose from providing the ultimate in flexibility, all of your system needs are covered.

Peakx limiters

Peakx limiters provide the ultimate in performance and protection for your entire system. This advanced algorithm was specifically developed and tuned to work with this amplifier and power-supply to achieve higher SPL will less audible artifacts. This means less distortion, less shutdowns, and maximum safe power delivered to your speakers. The Peakx limiters can be easily turned on or off by channel right from the front panel eliminating the need to be digging around in the back of the dark rack.

Crown XLS1000 DriveCore Series Power Amp Features:

XLS High Performance, Lightweight Class D amp weighs less than 11 lb.

Integrated PureBand Crossover System for better performance and control

Peakx Limiters provide maximum output while protecting your speakers

XLR, 1/4", RCA inputs provide outstanding flexibility

1/4" Inputs can be used as loop-thrus to distribute signal to additional amplifiers Efficient forced-air fans prevent excessive thermal buildup

Electronically balanced XLR inputs; touchproof binding post and Speakon outputs

Precision detented level controls, power switch, power LED, and six LEDs indicate signal, clip and fault for each channel

Three-Year, No-Fault, Fully Transferable Warranty completely protects your investment and guarantees its specifications

SMS303 Tantek Tanrak (9 module Modular FX):

- Comp-Lim2

- Parametric Equaliser

- Enhancer

- Modulation Oscillator

Info:

Mid 1980's Tantek, Tanrak Studio Effects Rack which was available in kit form or ready built. These were bought as kits and put together by an electronics engineer. On the face of it, they're simple analogue effects - a bit old-fashioned, really - but that's the charm of them. They've perfectly useable and immediately accessible, so you'll have great fun fiddling with the settings - try sweeping the EQ frequency, or riding the delay time for on-the-fly munchkinisation, for instance.

Even better, you'll find new ways to patch the modules together. Everything - in, out and sidechain - is accessible from the rear panel (there's a default path from left to right across the rack if you don't want to use patch cords) so you can create LFO-modulated delay effects, frequency-sensitive compression ... you think of it, you can do it.

STEREO COMPRESSOR/LIMITER - A high quality stereo comp/limiter with variable input, slope, attack and release controls, and a switched 'key' input that can link both channels...handy for de-essing, ducking etc. It's pretty much 'invisible' when used as a limiter, only squeezing when the threshold is crossed (depending on the ratio setting). Great for laying vocal tracks, mix thickening, fattening up drums, percussions and bass. In fact, it can make anything sound 'phat' but still retains that important top-end clarity.

MODULATION OSCILLATOR - A CV modulation source whose features include sinewave output, variable duty cycle, key or CV controlled depth, triggerable sweeps and two independently variable outputs. Used with the muli-dealy to create chorus, flanging etc.

The Dirty Carter Electronic Sound Generating Instrument was designed by John Richards (Dirty Electronics) and Chris Carter from legendary Industrial pioneers Throbbing Gristle. It was produced for a special performance by Carter and the 25 strong Dirty Electronics Ensemble in 2010. It was originally designed as a touch controlled instrument with the player's skin resistance completing the circuit. This hard wired modification by A.S.M.O. gives more control and predictability by wiring all to the touch contacts to pots and switches. An additional low pass resonant filter has been added, LFO and an external CV socket for filter modulation.

The case is made of stained ply and the front panel is covered with black leatherette.

amorphica.com/networked.html

Group 4_

Aaron Onchi, Betty Sanchez, Roberto Gutierrez, Frank Durán , Belén Olaya García

Networked Fabrication for Urban Provocations.

Shifting Paradigms from Mass Production to Mass Customization

Computational architecture and design course

Conventional construction methods all depart from the basic premises of mass production: standardization, modulation and a production line. What these systems developed during the last two centuries fail to take into account are the evolutionary leaps and bounds the manufacturing industry has taken over the last decades. With the introduction of CNC technologies and rapid prototyping machines have altered the paradigms of fabrication forever. It is due to these new tools that it is now possible to create (n) amount of completely unique and different pieces with the same amount of energy and material that is required to create (n) identical pieces. The possibilities for implementation of new forms, textures, materials and languages are infinite due to the versatility that these new tools offer a growing network of architects, designers, fabricators that are integrating them into their professional practices to generate unique and precise objects that respond to countless data and real-life conditions.

Instructors:

Monika Wittig [ LaN, IaaC ]

Shane Salisbury [ LaN, IaaC ]

Filippo Moroni [ SOLIDO, Politecnico di Milano ]

MS Josh Updyke [ Advanced Manufacturing Institute, KSU, Protei ]

Aaron Gutiérrez Cortes [ Amorphica ]

Specification

Coach Model MAN 18.350 HOCL/R

Chassis Length 11,850 mm

Chassis Width 2,526 mm

GVW 18,200 kg

Engine Type

Vertical, Water Cooled 6-cylinder 4-stroke Diesel Engine

With Common Rail Injection,

Exhaust Turbocharger and Intercooler

ECR, Replaceable Cylinders Liners

Engine Model MAN D2066 LUH13 Euro 4

Displacement 10,518 c.c

Maximum Output 257 kW (350 hp) @ 1,700 rpm

Maximum Torque 1,750 Nm @ 1,000-1,400 rpm

Bore 120 mm

Stroke 155 mm

Fuel Capacity 300 dm³

Transmission ZF 6S 1900 BO 6-speed Synchromesh Manual Transmission

ZF 6 HP 504C 6-speed Automatic Transmission

Voith D864.5 4-speed Automatic Transmission

Drive Axle MAN HY-1336-B

Suspension Capacity 13,000 kg

Front Axle MAN V9-82 SL

Suspension Capacity 8,200 kg

Brake

Dual Circuit Air Brake System to ADR Directives by Wabco

Front and Rear Axle Disc Brakes

Electronic brake system EBS (ABS, TCS)

Auxiliary Brake Manual Transmission: Engine Brake Valve (EBV)

Automatic Transmission: Integrated Retarder and

Water Cooled with Electric Pressure Modulation

Suspension

Air suspension with 6 identical rolling seals

With Integrated Elastic Stroke Limiter

Electronically Controlled Constant Entrance Height

Suspension Characteristics Under All Load Conditions

Front Suspension 2 x Air Bellows

2 x Shock Absorbers

1 x Level Control Values

1 x Stabilizers

Rear Suspension 4 x Air Bellows

4 x Shock Absorbers

2 x Level Control Values

1 x Stabilizers

Blacktron Gold - Listening and Assault Unit

Spacecraft equipped with:

- stereo cockpit

- optoechoic head

- white noise generator

- modulation metronome

- dual megabass cannon

- large aperture antenna with phrase scanning

- dual IR (iridium) jam-session-er

- powerful pro-tone torpedo

- dual frequency Hi-Fi-per sonic missiles

Video here: www.youtube.com/watch?v=XrHkvvtrXhA

The Crazy Looper is a small handmade device that allows you the create real-time noise loops with a fast modulation metallic effect.

A regular location for taking photos at. I cross this point twice on bicycle commuting days.

The vehicle's rear lights appears as a dashed line. These are LED rear lights that derive their tail lamp illumination setting via Pulse Width Modulation control (they are turned on/off at a high frequency). The LEDs are operated 'full on' when used as a brake light.

From the early years of transistor radio history... this one has 6 whole transistors! They were very expensive in the late 1950's and started getting cheaper in the 1960's.

At the Cluny Museum, medieval culture showcases its ancestral knowledge. It took five centuries to discover that the thymus and the genitals are connected, as seen in this statue of the first man to experience desire, through a dream about a mythical serpent.....

Within the thymus, regulation of the cellular crosstalk directing T cell development depends on spatial interactions within specialized niches. To create a spatially defined map of tissue niches guiding human postnatal T cell development, we employed the multidimensional imaging platform co-detection by indexing (CODEX) as well as cellular indexing of transcriptomes and epitopes sequencing (CITE-seq) and assay for transposase accessible chromatin sequencing (ATAC-seq). We generated age-matched 4- to 5-month-old human postnatal thymus datasets for male and female donors, identifying significant sex differences in both T cell and thymus biology. We demonstrate a possible role for JAG ligands in directing thymic-like dendritic cell development, identify important functions of a population of extracellular matrix (ECM)− fibroblasts, and characterize the medullary niches surrounding Hassall’s corpuscles. Together, these data represent an age-matched spatial multiomic resource to investigate how sex-based differences in thymus regulation and T cell development arise, providing an essential resource to understand the mechanisms underlying immune function and dysfunction in males and females.

The thymus is the primary organ responsible for the generation and selection of mature, functional, and self-tolerant T cells.1 Effective T cell development is a critical component of our immune system’s ability to accurately and exclusively identify and kill foreign entities such as pathogens. During early postnatal T cell development—the period in life when T cell development is most active2—thymic seeding progenitors migrate to the thymus and mature into thymocytes. Thymic architecture is highly organized to provide spatially defined, stage-specific signaling cues to migrating thymocytes that guide development toward functional mature T cells.3,4,5,6

Recent single-cell sequencing resources demonstrating the diversity of human thymus tissue are incongruous with our current framework of thymus structure and organization,7,8,9,10,11,12,13,14,15,16,17,18,19 which describe a general migratory path thymocytes take through the cortex and medulla during conventional αβT cell development. Spatial transcriptomic sequencing of human thymus has demonstrated a deeper granularity of thymic niches and their evolution during fetal development to support different waves of non-conventional T cells.19,20 However, our understanding of how human postnatal thymus niches support conventional and non-conventional T cell development, T-lineage branching, and alternative lineage development remains limited.3,4,6 T cells generated at this stage of postnatal human development will become the foundation of our immune system, patrolling the body for decades.21 Thus, insights into early postnatal thymus niche biology are crucial to understand how our adaptive immune system is built and how perturbations in postnatal T cell development may emerge as immune dysfunction later in life.

To create a spatially defined map of tissue niches guiding human postnatal T and alternative lineage cell development, we employed multi-dimensional spatial proteomic imaging using co-detection by indexing (CODEX),22,23 single-cell transcriptomic-proteomic profiling using cellular indexing of transcriptomes and epitopes sequencing (CITE-seq),24 and single-cell assay for transposase accessible chromatin sequencing (ATAC-seq).25 Given the emerging recognition of sex differences in thymus gene expression and function,26,27,28,29,30,31 we collected and analyzed samples from male and female donors. Our analysis identifies significant sex differences during early postnatal development that affect T cell and thymus biology through common and cell type-specific mechanisms. Additionally, we highlight key cell types contributing to thymic involution that exhibit sex-based differences in thymic growth and early transition toward adipogenesis. These data suggest that kinetic differences in thymic involution are present between sexes and, importantly, that mechanisms driving thymic involution begin early in life. Altogether, these data represent a powerful age-matched spatial multiomic resource to investigate how sex-based differences in thymus biology and T cell development arise, and how they contribute to sex differences in diseases caused by immune dysfunction.

Results

Spatial multiomic profiling of human postnatal thymus identifies sex-based differences in T cells and thymus biology

We performed single-cell CITE-seq, ATAC-seq, and CODEX imaging on 4–33 months human postnatal thymuses, including 6 (3 female and 3 male) 4- to 5-month-old age-matched samples (Table S1). Each donor sample was processed simultaneously for CODEX imaging and sequencing (Figure 1A). We included a comprehensive 137 antibody panel (Data S1), allowing us to compare epigenomic, transcriptomic, and proteomic expression kinetics across developing thymocytes and enabling direct comparison of cells identified via phenotypic expression in CODEX with cells captured via CITE-seq. Prior to sequencing, we enriched CD45− non-hematopoietic cells and CD25+CD8− regulatory T (Treg) cells to ensure coverage of low-abundance cell types. After quality control and computational merging of individually sequenced patient datasets, we obtained a total of 74,334 cells with CITE-seq, including 19,434 non-T-lineage cells, and captured 25,717 nuclei with ATAC-seq. Importantly, cell proximity in CODEX tissue niches was used to screen predicted receptor-ligand interactions.

Figure 1 Spatial multiomic analysis identifies sex-biased characteristics of thymic niches

Show full captionFigure viewer

CITE-seq cells were clustered based on transcriptional expression and annotated based on marker gene and surface protein expression (Figure S1A; Table S2).7,8 ATAC-seq clusters were computationally labeled using CITE-seq reference cluster labels, which identified 34 ATAC-seq cluster transfer labels for dataset integration (Figures 1B and S1B). We captured 54,900 thymocytes spanning development from early thymic progenitors (ETPs) to mature single positive (SP) T cells, immature innate cells, innate-like cells, and Tregs. We identified three Treg populations expressing canonical lineage markers, namely Treg progenitors (Pro-Tregs), thymic Tregs (tTregs), and recirculating/resident Tregs (rrTregs).32 We also identified antigen-presenting cells, including B cells, mast cells, monocytes, and six populations of dendritic cells (DCs).33 In addition to the activated DCs (aDCs), plasmacytoid DCs (pDCs), DC1, and DC2/3 populations described by Park et al.,7 we found proliferating populations of pDCs and DC1. We also captured 7,093 epithelial cells, including cortical epithelial cells (cTECs), medullary epithelial cells (mTECs), activated mTECs, and mimetic TECs.

Importantly, we captured 7,721 mesenchymal cells, which contribute to negative selection and thymic involution.9,19,34,35,36 Subclustering identifies important mesenchymal cell types, including two populations of endothelial cells (ECs) defined by differential expression of Notch ligands (ECs, ECs (Notch)). Additionally, we identified lymphatic ECs (LECs), pericytes, vascular smooth muscle cells (VSMCs), and five distinct fibroblast cell types, including DPP4+ capsular fibroblasts (DPP4+ capFibs), capsule fibroblasts (capFibs), medullary fibroblasts (mFibs), KRT+ fibroblasts (KRT+ Fibs), and proliferating fibroblasts (Fibs (P)).

We imaged each tissue sample with a custom 48 antibody CODEX panel to study the architecture and function of niches guiding thymocyte development, aiming to define the niche characteristics guiding T-lineage branch points. Stage-specific thymocyte phenotyping markers (CD62L, CCR7, CD1A, CD5, CD7, CD4, CD8, CD3, CD45RO, CD45RA, FOXP3, and SATB1) identified CD3+ double positive cells (DPs) undergoing T-lineage commitment toward CD4 or CD8 T cells. Phenotyping markers for non-T-lineage hematopoietic cells (CD19, CD11c, CD11b, and CD68), epithelial cells (EPCAM and KRT5/8), mural cells (MCAM and SMA), ECs (CD31), and fibroblasts (PDGFRA) identified the remaining major cell types defining thymic niche architecture. Finally, we included functional markers to define patterns of antigen presentation (CD86), human leukocyte antigen (HLA) class I and II expression (HLA-ABC and HLA-DR,DP,DQ), adhesion ligands (ICAM and VCAM), Notch ligands (DLL1, DLL4, JAG1, and JAG2), T cell activation (PD-1), self-tolerance (PD-L1), proliferation (Ki67), and enzymatic regulation (15-PDGH). In sum, our CODEX panel enabled investigation of spatially regulated mechanisms directing human T cell development.

Using neural-network-driven cell segmentation and Leiden-based clustering,23 we identified individual cells within thymic tissue for each sample (Figure S1C). We annotated cell types based on tissue location and phenotypic expression compared with CITE-seq clusters (Figure 1C), performed proximity-based neighborhood clustering to identify niches,23 and annotated niches based on location and cell type composition (Figure 1D; Figure S1D). This analysis quantified proximity-based cell-cell interactions (Figure S1E) and served as a platform to interrogate spatially defined thymic niche biology via integrated sequencing-imaging analysis.

Because of known sex differences in thymus and T cell gene expression,31 we compared our age-matched male and female samples separately. In line with prior reports of sex-biased gene expression on autosomes,37,38,39,40 only 2% of male differentially expressed genes (DEGs) were found on the Y chromosome and 0.3% of female DEGs were found on the X chromosome (Tables S3 and S4). Gene set enrichment analysis (GSEA) on male vs. female cells for each cell type identified pathways commonly upregulated in either sex (Figure 1E; Data S1). Pathways differentially regulated across hematopoietic, epithelial, and stromal cells represent cell-intrinsic sex-based differences. Female cells have higher gene expression of transcription, energy regulation, and antigen presentation. Male cells, by contrast, have increased gene expression of proinflammatory signaling, amino acid metabolism, and G protein-coupled receptors (GPCR) signaling. The top differentially expressed energy regulation and metabolism pathways were similarly sex-biased in human kidney,41 suggesting multiple organs show consistent sex-biased enrichment of pathways linked to metabolism and energy production. Our data align with sex-biased trends identified in human induced pluripotent stem cell (iPSC) lines42 and other human organs,43 indicating these pathways often differ between male and female cells across various cell types.

By contrast, some pathways showed cell type-specific sex-biased enrichment. Female T and hematopoietic cells showed enrichment of interferon signaling, and female fibroblast and perivascular cells were enriched in extracellular matrix (ECM)-centric pathways (Figure 1E). Our dataset also identified differential sex-specific pathway enrichment between cell types. Gene expression indicated higher cytokine signaling in T cells and hematopoietic cells in females and in epithelial and mesenchymal cells in males (Figure 1E). These data show significant gene expression differences in male and female thymic cells. To demonstrate sex differences at the proteomic level, we identified genes with a log fold change greater than 1 that contributed to increased chemokine signaling in male T cells. CXCR4, an important chemokine receptor in thymocyte migration and development, had increased expression in male progenitor T (pro-T) cells, which we confirmed via flow cytometry (3 male, 3 female; p = 0.03; Figure S1F). As higher levels of cytokine and interferon signaling have been previously shown to influence thymus and T cell biology,44,45 our data suggest male and female T cells develop in different signaling environments and may respond differently to cytokine stimuli.

Next, we quantified cell type abundance within male and female tissues, demonstrating differences in cortical and medullary cell distributions between sexes. When normalized to the total number of cells per lobe, female thymus lobes contained significantly more DPs (p = 0.011) and cTECs (p = 0.0023). In males, we found significantly more SPs (p = 4.2 × 10−4), CD3+ DPs (p = 9.9 × 10−4), activated mTECs (p = 0.0014), and VSMCs (p = 2.4 × 10−6) (Figure 1F). Given that thymus lobules with more DPs and cTECs would have a greater proportion of cells undergoing positive selection and lobules with more medullary cells would have more cells undergoing negative selection, these data suggest that sex differences in cell type abundance may influence the resources directed toward specific stages of thymocyte selection. Alternatively, these results may suggest that male and female thymuses are developmentally asynchronous, with males exhibiting faster growth and involution kinetics, resulting in decreased cortical-to-medullary ratios even in early neonatal stages. We focused further analyses on sequential developmental niches, including analysis of sex differences in cell types and niches at each stage.

JAG1 skews ETP development toward thymic DCs

We first analyzed the cortico-medullary junction (CMJ) where cells home to the thymus (Figure 2A). This region recruits and supports ETPs10 and is composed of ECs, VSMCs, and pericytes expressing the Notch ligand JAG1 (Figures 2B and 2C). CITE-seq demonstrated that the cell adhesion molecule used by ETPs to enter the thymus, CD62L, is quickly downregulated upon CMJ entrance through the vasculature (Figure S2A). However, recently immigrated CD62L+ double negative cells are frequently located in the subcapsular zone (Figure S2B), suggesting that ETPs enter the thymus and rapidly migrate to a subcapsular niche where DLL4, a more potent Notch ligand, is highly expressed on fibroblasts and subcapsular epithelial cells (Figures 2D and S2C). However, the concentrated presence of JAG1 at the entry point indicates that ETPs are first exposed to this Notch ligand.

Figure 2 Thymic progenitors entering via the corticomedullary junction are exposed to a gradient of Notch ligands, which influence lineage specification

Show full captionFigure viewer

CellChat46 pathway analysis showed that JAG1-NOTCH1 interactions between endothelial and perivascular cells are enriched with ETPs (Figure 2E), while JAG1-NOTCH2 and JAG1-NOTCH3 interactions are enriched with DC1, DC1 (P), DC2/3, and aDCs (Figures 2E–2G). These data suggest that JAG1 could induce commitment toward other hematopoietic lineages, such as pDCs, conventional DCs (cDCs), or macrophages, which are known to develop within the thymus.10 As JAG ligands induce weaker Notch induction,47,48,49,50 we hypothesized that early contact with ETPs could maintain T-lineage potential while cells migrate toward DLL4 in the subcapsular niche.

We first analyzed the ability of the four thymic Notch ligands to induce T-lineage commitment or alternative lineage development from cord-blood-derived CD34+ hematopoietic stem and progenitor cells (HSPCs) in a defined, feeder-free culture system44 (Figure 2H). We included titrated concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), which is produced by mast cells at the CMJ, to support DC development.51 We found that only DLL1 and DLL4 ligands induce T-lineage commitment, whereas JAG ligands or no ligand controls supported myeloid cell development and did not induce T-lineage commitment (Figure S2D). Specifically, JAG ligands with GM-CSF skewed CD68+ DC development toward CD14− DC1 cells, while no ligand controls skewed CD68+ DC development toward CD14+ DC2/3 cells (Figures 2I and S2E).

Next, to test our hypothesis that Notch signals via JAG1 ligands could act as a bridge toward later DLL4 interactions, we analyzed cells grown on JAG1 for 3, 5, or 7 days prior to DLL4 transfer (Figure 2J). We found that cells cultured on JAG ligands or no ligands for 3 days maintained reduced T-lineage commitment compared with DLL1 or DLL4 cells (pJAG1 = 0.033; pJAG2 = 0.017), whereas cells cultured on JAG ligands for longer than 3 days lost T-lineage potential (Figure 2K), indicating that JAG ligands could not support T-lineage potential.

We next analyzed the contribution of different Notch ligands to the development of male and female ETPs (Figures S2F and S2G). Our data suggest that JAG ligand interactions are more abundant and diverse in females, with JAG1-NOTCH1 interactions enriched in female ETPs and DLL4 interactions enriched in male ETPs.

Together, these data suggest that timely migration from the CMJ to DLL4 ligands at the subcapsular zone is critical for T-lineage commitment, and exposure to JAG ligands at the CMJ can guide alternative lineage development toward thymic-derived DCs. Our data further demonstrate previously unrecognized sex-biased regulation by Notch ligands.

Analysis of the subcapsular zone identifies sex-based differences in fibroblast regulation of DP development and thymus growth

From the CMJ, ETPs migrate to the subcapsular zone via a CCL25-CCR9 chemokine gradient established by cTECs and directed to pro-T, DP (P), and DP2 (Q), but not DP1 (Q) cells (Figure 3A; Figure S3A). The subcapsular niche consists of JAG1+ VCAM1+ DCs, cTECs, capsular fibroblasts, DPP4+ capsular fibroblasts, and proliferating fibroblasts, which secrete and maintain spatially regulated ECM ligands to support sequential thymocyte development (Figures 3B and 3C; Figure S3B and S3C).

Figure 3 Fibroblasts in the subcapsular zone contribute to regulation of thymus biology and T cell progenitor development

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GSEA showed that DPP4+ capsule fibroblasts were enriched in HSP90 chaperone cycle for steroid hormone receptors (padjusted = 0.0065; 18/52 pathway genes significantly upregulated) (Data S1), suggesting an enhanced response to steroid hormones and supporting their role in sex hormone-based thymic involution.9 By contrast, capFibs were enriched for genes related to cytokine (interleukin [IL]-33, padjusted = 1.50 × 10−6; IL-34, padjusted = 3.56 × 10−7) and chemokine signaling (CCL2, padjusted = 5.10 × 10−40; CXCL3, padjusted = 0.020; CXCL12, padjusted = 1.78 × 10−8; CXCL14, padjusted = 3.63 × 10−15), functions previously attributed to TECs. Furthermore, CellChat identified cortical fibroblasts as major contributors to insulin growth factor (IGF) signaling through predicted signaling to cTECs, which are found in close proximity in the cortex (Figure S3D), via IGF2-IGF1R and IGF1-IGF1R axes, and to ETPs and β-selection cells, which were found under the capsule (Figure S2B), via an IGF2-IGF2R axis (Figures 3D–3F).

We next explored the role of proliferating fibroblasts. GSEA comparisons between capFibs and Fibs (P) showed marked differences in signal transduction pathways. CapFibs resembled traditional fibroblasts, which upregulate tyrosine kinase, angiogenesis, and ECM regulation and deposition pathways, whereas Fib (P) upregulates WNT signaling and cell sensing pathways, including genes involved in transient receptor potential (TRP) channels in the stimuli sensing channels pathway and taste receptors (TASRs) (Figure 3G; Data S1). Interestingly, CODEX images identified ECM− PDGFRa+ fibroblasts lacking extra domain A fibronectin (EDA-FN) expression, indicating that Fibs (P) are not involved in fibrotic matrix deposition unlike capFibs (Figure 3H; Figure S3B). Fibs (P) form a network of PDGFRa+ cells throughout the cortex that does not overlap with the cTEC network, yet maintain cell-cell contact in specific niches and often localize near cortical capillaries (Figure S3D).

We found sex-specific differences in vascular endothelial growth factor A (VEGFA) signaling within ECM− fibroblasts (Fib (P)) and other mesenchymal cells. Although all thymic fibroblasts produce the angiogenesis growth factor VEGFA, male fibroblasts express more than female cells (Fibs (P): padjusted = 0.0306; DPP4+ capFibs: padjusted = 0.0318; mFibs: padjusted = 1.85 × 10−6) (Figure 3I). Given that postnatal male thymuses are larger than female thymuses in humans and primates26 (Figure S3E), male fibroblasts may provide increased VEGFA to support angiogenesis and rapid thymic growth observed during postnatal development.52 Additionally, male mFibs have higher expression of FGF7 (padjusted = 0.0154), which regulates thymus size.53 CellChat predicts that male Fibs (P) are enriched in FGF10 compared with females, which supports cTEC proliferation and vascular growth,53,54 and only male VSMCs express FGF18 (Figures S3F–S3H). These sex biases in fibroblast growth factor (FGF) gene expression may contribute to the larger size of early postnatal male thymuses by stimulating epithelial and EC growth and proliferation.

Comparison of DEGs between male and female mesenchymal cells found increased expression of adipogenesis, cytokine, and GPCR signaling pathways in DPP4+ capFibs (Figure 3J). We also found increased expression of APOD, a gene associated with androgen, estrogen, progesterone, and glucocorticoid signaling,55,56 across male fibroblast populations (Fibs (P): padjusted = 2.18 × 10−26, mFibs: padjusted = 8.45 × 10−32) (Figure S3I). Given the association of hormone signaling with thymic involution,29,52,57 these findings suggest early initiation of thymic involution in postnatal males.

In sum, we identified three roles for fibroblasts within the subcapsular niche: maintaining tissue structure and organization via ECM and chemokine signaling, directly regulating cTEC maintenance and expansion, and potentially coordinating T cell development directly through growth factors and cell-cell interactions.

Human postnatal thymocytes may self-select in the cortex to support positive selection of conventional αβT cells

Upon exiting the subcapsular zone, DPs migrate into the inner cortex toward the medulla, where they receive positive selection signals that guide T-lineage branching toward CD4 or CD8 SP cells (Figure 4A). For DPs to transition toward the CD4 lineage, cells must receive T cell receptor (TCR) stimulation through HLA class II interactions, yet previous mouse studies have shown transcriptional downregulation of HLA class I and II in DPs.58,59 Low transcriptional expression is hypothesized to prevent thymocyte-thymocyte self-selection during positive selection, necessitating DP interactions with cTECs to receive positive selection signals.

Figure 4 HLA class I and II interactions may support thymocyte positive selection in the inner cortical zone

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Analogous to mouse literature, quiescent human DPs do not express HLA class II transcripts and have closed CIITA promoters (Figures 4B and 4C). Despite the lack of class II mRNA, thymocytes express low levels of HLA class II protein throughout development (Figure 4B). Additionally, in contrast to mouse data, we observe constitutive class I mRNA expression, which increased as cells transitioned toward SPs (Figure 4D). This is consistent with ATAC-seq data demonstrating that the B2M promoter is open throughout thymocyte development (Figure 4E). We confirmed HLA expression via flow cytometry and found that approximately 25% of DPs express both class I and II, and over 65% of DPs are class I+ (Figure S4A). Thus, thymocyte self-selection within the cortex could support positive selection. In support of this notion, CODEX enabled us to identify locations within the cortex devoid of epithelial, fibroblast, endothelial, or DCs but packed with DPs expressing class II+ molecules concentrated at cell junctions (Figure 4F). We confirmed the absence of spindle-like cTEC projections in this niche via confocal imaging (Figure 4G). Additionally, we quantified cell-cell interactions and identified a niche (positive selection niche 1) consisting of class II+ DPs and CD3+ DPs and a niche (self-selection niche) containing mainly class II+ DPs (Figure 1D). Finally, we sorted thymocytes to isolate immature DPs (CD4+CD8+CD3−TCR−) and mature DPs (CD4+CD8+CD3+TCR+) from three donors and cultured them for 7 days in a feeder-free assay. In the absence of epithelial cells, both immature and mature DPs upregulate HLA class II proteins (Figure 4H), and immature DPs continue to mature along their developmental pathway, as indicated by increased percentage of CD27+ DPs in culture after 7 days (Figure 4I).

Next, we identified a niche that directs T-lineage commitment toward CD4 or CD8SPs. We performed differential gene expression analysis on clusters representing this lineage branch point to identify markers for our CODEX panel (Figure S4B). We found SATB1 expression increased as DPs transitioned toward SPs (Figure S4C), and compared with CD8SP transition cells, CD4SP transition cells had higher expression of this master transcription factor60 (Figures S4D and S4E). Imaging analysis confirmed increased SATB1 expression coincides with CD3 upregulation, consistent with a role in late DP development and lineage branching (Figure 4J).7 Neighborhood analysis identified a niche enriched for mature CD3+ DPs in the inner cortex, suggesting that there either exists a niche specifically for late DP development and CD4 lineage transition or that cells are pre-disposed to CD4 lineage development through their TCR and migrate as clonal populations after proliferation at the outer cortex.

We compared cortical niche organization between sexes and found differences in niche organization supporting conventional T cell development, self-selection, and cross presentation. Females showed increased neighborhood interactions between the cortical DC niche containing JAG1+ VCAM+ DCs and the mature DP niche containing CD3+ DPs, the positive selection niche 1 containing class II+ DP cells and CD3+ DP cells, and the positive selection niche 3 containing DCs and DPs (Figure S4F) as well as increased cell-cell interactions between cTECs and class II+ DPs (Figures S4G and S4H). Conversely, males had increased cell-cell interactions between cTECs and CD3+ DPs (Figures S4G and S4H). These data suggest that the proportionally larger female cortex could increase cross presentation from DCs and cTECs to class II+ DPs, possibly facilitating greater use of self-selection as an alternative mechanism for positive selection.

Taken together, spatial multiomic analysis of the inner cortex identified cortical niches supporting specific stages of DP development, including three positive selection niches, a specialized niche for self-selection, and a mature DP niche thymocytes migrate through prior to entering the medulla.

Spatial multiomics identifies key mechanisms regulating negative selection niches in the medulla

Mature DPs enter the medulla, an environment specialized for negative selection, and transition toward CD4 or CD8 lineages (Figure 5A). Within the medulla, cells specialized for negative selection localize around keratinized structures called Hassall’s corpuscles (HCs).61 HCs appear during late prenatal development and are abundant in human postnatal thymuses but rare in mice.62 Here, we demonstrate that HCs can be divided into three major components: an external epithelial border of highly keratinized cells, an inner border of cells expressing prostaglandin-degrading enzyme 15-PGDH (HPGD), and a central PDGFRa+ mass (Figure 5B). HCs produce thymic stromal lymphopoietin (TSLP),61 an analog of IL-7, which activates DCs to increase expression of class II and co-stimulatory molecules CD80 and CD86. Importantly, subclustering stromal populations identified a population of KRT+ fibroblasts resembling cells undergoing epithelial-to-mesenchymal transition (EMT)63 (Figures S5A and S5B). CITE-seq identified TSLP and 15-PGDH mRNA expression in KRT+ Fibs, mFibs, mTECs, activated mTECs, and aDCs (Figure 5C), implicating these cell types as potential contributors to the function of HCs. Finally, given the inner layer of 15-PGDH+ cells, we explored the role of prostaglandin signaling regulation within the medulla. We found that DC1 cells express high levels of PGE2, whereas DC2/3 cells and monocytes express the PTGER2 and PTGER4 receptors, and aDCs express the PTGER3 receptor (Figure 5C), suggesting prostaglandin signaling is a major regulator of DC activity near HCs.

Figure 5 HCs represent scalable organizing centers for negative selection in the neonatal thymic medulla

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CODEX imaging suggests HCs act as sub-medullary organizational centers to segregate the inner medulla into specialized niches for negative selection. CD86+ APCs, a subset of which express the co-stimulatory ligand CD40, localize near HCs and in direct contact with CD45RA+ mature SPs (Figure 5D; Figure S5C). In addition, approximately 30% of medullary area is composed of CD19+ B cells,64 which cluster into niches surrounding HCs (Figure S5D). These B cells are found in close contact with—and are often enveloped within—mTECs, potentially facilitating cross presentation with epithelial cells (Figure 5E). These results suggest thymic B cells may comprise an important source of antigen presentation for negative selection.64,65 We quantified medullary neighborhoods and identified six niches, including an mTEC maturation niche, a cross-presentation niche, and four niches specialized for negative selection, which vary in relative location to HCs or the CMJ, as well as their composition of APCs, epithelial, and T cells (Figure 1D; Figure S1D).

Negative selection niches surrounding HCs play a key role in conventional T cell and tTreg development.61 We enriched CD25+ cells for sequencing and found a population of CD25hi pro-Tregs expressing canonical Treg markers CTLA-4, TNFRSF1B (TNFR2), and TNFRSF4 (OX40); positive/negative selection markers (ITM2A, RANBP1, NCL, NME1, MIF, and ATP5G1); Treg developmental long non-coding RNA (MIR155HG)66,67,68,69; and other markers described in mice (Figure S5E). Whereas pro-Tregs expressed high levels of pro-apoptotic gene BCL2L11, mature tTreg subsets expressed the anti-apoptotic gene BCL2. Gene network reconstruction via SCENIC70 identified transcription factor networks activated during pro-Treg to tTreg transition (Figure 5F).

The thymus also contains mature, highly activated Tregs, labeled as rrTregs, believed to have recirculated from the periphery.71,72 rrTregs lack expression of CCR7 or thymic egress markers (KLF2 and S1PR1) but express IL1R2 (Figure S5F), which sequesters the inflammatory cytokine IL-1β to reduce local concentrations.73 CODEX imaging identified tTregs and rrTregs dispersed throughout the medulla, with rrTregs primarily adjacent to CD68+ DCs (Figure 5G). CellChat supported the potential of rrTregs to sequester inflammatory cytokines through interactions with DC2/3 via an IL-1β-IL-1R2 axis (Figure S5G). rrTregs also exhibited a tissue resident Treg phenotype (BATFhigh CCR8+) associated with wound healing and tissue regeneration function,74 and expressed remodeling and tissue repair-related genes such as matrix metalloproteinase enzymes (MMP25 and ADAM19) (Figure S5H). Overall, these findings illustrate Treg diversity in the thymus with their developmental trajectories and functions yet to be elucidated.

Comparisons of male and female rrTregs showed that male rrTregs had higher expression of IL-4 and IL-13, heat shock factor protein 1 (HSF1), and IL-1 signaling pathways (Figure 5H), suggesting rrTreg-mediated regulation of IL-1R2-mediated anti-inflammatory feedback checkpoints is a more prominent mechanism in male tTreg development in early postnatal thymus. Notably, male-activated mTECs have higher expression of CD40 and tumor necrosis factor (TNF) inflammatory pathways than females, possibly resulting in higher rrTreg activity (Figure S5I).

Finally, as Tregs have been shown in mouse to contribute to thymic involution through JAG1,75 we explored sex-based differences in tTreg gene expression. GSEA showed male rrTregs and tTregs have higher expression of adipogenesis pathways (Figures 5H and 5I). Given the presence of cells undergoing EMT, our data underlie the aggressive timeline of thymic involution and suggest that sex-based differences in thymus functional decline begin early in life.

Our detailed examination of the medulla identifies several niches specialized for negative selection, cross presentation, and mTEC maturation around HCs and demonstrates sex biases in inflammatory pathways and thymic involution kinetics within these niches.

Discussion

We performed spatial multiomics to construct a tissue atlas of niches guiding T cell development in early human postnatal thymus. These datasets characterize how key developmental niches drive lineage branch decisions, identify a possible mechanism for conventional αβT cell development through self-selection, and suggest additional functions for mesenchymal cell types governing thymus biology. Furthermore, we discovered several sex-specific differences in thymus cell and niche biology. As T cell development is a dynamic migratory process, knowledge of cell position in combination with proteomic, transcriptomic, and epigenomic sequencing data provides an invaluable resource to predict niche-specific signaling cues directing T cell development, and mechanisms responsible for maintaining tissue structure and directing thymic involution.

We describe an approach to sequencing analysis using multidimensional imaging to establish benchmarks for the location, ligand expression, and composition of key niches in T cell development. This enables us to analyze cell-cell interactions guided by niche composition, identifying physiologically relevant ligand-receptor interactions based on cell proximity within the tissue. Ultimately, this approach maps epigenomic, transcriptomic, and proteomic data to distinct tissue niches at single-cell resolution. Furthermore, we included equal numbers of male and female age-matched thymus samples, enabling comparison between sexes across platform modalities. Our analysis of sex-matched human early postnatal thymus demonstrates the highly plastic nature of thymus lobule organization and resource dedication. Each niche responds to sex-biased developmental kinetics, supporting robust T cell development to ultimately produce functional immune systems in different manners (Figure 6). The findings herein describe only a subset of the data, and we encourage the community to capitalize on this resource to provide further insight into sex differences and targeted niche-specific inquiries.

Figure 6 The human early postnatal thymus lobule is spatially organized into sex-biased niches to support stage-specific T cell development

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In our analysis of Notch ligands, we complemented our in silico approach with in vitro analysis. Our analysis suggests that JAG1 at the CMJ cannot support T-lineage commitment as cells migrate toward the subcapsular zone but instead skew alternative lineage development toward a CD14− DC1 subset (Figure 6). CD14 expression on DCs is linked with increased inflammatory cytokine production,76 suggesting that JAG ligands promote non-inflammatory DC phenotypes. These results highlight the importance of precise Notch signaling strength and timing in the thymus and emphasize the need for strict spatial control of different Notch ligands within thymic niches. Our observation of high JAG1 expression in the medulla and decreased DLL4 expression on cTECs outside the subcapsular zone aligns with previous studies on human postnatal thymus.77

In the subcapsular zone, we characterize the important roles of specialized fibroblasts. DPP4+ capFibs, described in mouse as cells with progenitor and anti-fibrotic potential,78,79,80,81,82 are observed as a fibroblast subset responsive to changes in systemic hormone levels. Since thymic function and involution are regulated by sex hormone levels,57,83,84,85 DPP4+ capFibs likely control these processes and are potential targets for addressing age-related thymic involution.86 Previously, only medullary fibroblasts were linked to thymocyte development and selection in the medulla.82 We demonstrate that capFibs may directly support thymocyte development in the cortex by producing growth factors like IGF2 (Figure 6). Blocking IGF2 signaling arrests thymocytes at the double negative stage,87 and our data identify capFibs as the IGF2 source, suggesting capFibs as an additional cell source of cytokines and growth factors for in vitro developmental systems. Finally, we demonstrate that ECM profiles of thymic fibroblasts are tightly regulated based on spatial localization. Future work should characterize how tissue stiffness changes as thymocytes migrate through developmental thymic niches to improve biomaterial strategies for in vitro T cell development.88

Furthermore, we identify a population of ECM− cortical fibroblasts that are enriched in cell sensing pathways, such as TASRs and TRP channels. Interestingly, TASRs regulate cell responses to local soluble substances, such as glucose, modulating release of hormones and other signaling molecules.89 Similarly, TRP channels play roles in cell sensing, such as pheromone signaling, nociception, temperature sensation, and osmoregulation.90 Given the proximity of these cells to vasculature in the cortex, Fibs (P) may play a critical role as regulatory cells by sensing environmental changes and modulating thymus size (Figure 6). Their lack of ECM production and network-like structure resemble fibroblast reticular cells (FRCs) in the lymph node, which rapidly proliferate and remodel the cortex during infection.91 Our data are generated from early postnatal thymus samples, an age with active T cell development, suggesting these fibroblasts expand the thymic cortex similarly to FRCs during infection, signaling through FGF and IGF to stromal and epithelial cells to orchestrate remodeling.

While the dogma in thymocyte positive selection suggests that DPs downregulate class II RNA to prevent self-selection and force interactions with cTECs,58,59 several studies suggest that T-lineage cells can select off each other to support CD4 T cell development.20,92,93,94 Here, we describe an inner cortical niche where class II+ DPs reside that may support positive selection via DP-DP self-selection (Figure 6). We show that immature DPs cultured without epithelial cells upregulate HLA class II and continue to mature and receive positive selection signals. Additionally, upregulated SATB1 expression identifies mature DPs in an inner cortical niche and the CD4 branch of their progeny, suggesting it may determine early lineage specificity. Future work should investigate critical features of this niche and SATB1’s role in thymocyte development.

Within the medulla, we identified a niche adjacent to HCs specialized for negative selection and highlighted the role of rrTregs in modulating the medullary inflammatory environment (Figure 6). The abundance of HCs in human but not mouse, and their proximity to negative selection niches, suggests these structures evolved to provide niche-level organization within the larger human medulla or to regulate negative selection more stringently in longer-lived species.

Comparing male and female tissue showed sex differences in both T cell and thymus biology. Studies on post-pubertal males and females show that sex hormones differentially regulate thymic involution between sexes,26,27,28,29,30,52,57,84,86 and that androgen blockers increase FOXN1 expression, thymic involution, and increased rejuvenation.29,30,52,84,86 Additionally, older males produce fewer recent thymic emigrants and have smaller thymuses compared with females.26,28 Some studies describe decreased numbers of AIRE+ mTECs with age and in females,95 potentially predisposing females who maintain greater thymic function later in life to autoimmune disease.29 These studies also observe less interlobular fat in young female thymus,26 suggesting differences in thymic involution kinetics begin pre-puberty. However, current literature has not addressed transcript-level sex differences underlying functional differences in thymic and immune function. Our analysis uncovers that female thymic cells upregulate energy regulation, transcription, and antigen-presentation pathways, whereas male cells increase proinflammatory signaling, amino acid metabolism, and GPCR signaling. These cell metabolic differences align with transcript-level sex differences in other organs41,42,43 and highlight the need for sex-based cell culture optimization in in vitro T cell culture systems.

In addition to changes common to other organs,40,41 we identify thymus-specific differences affecting key processes in thymocyte development and training. Females have a larger proportion of cortical cells per lobule, aligning with lower thymic involution rates and a larger cortex/medulla ratio.26,27,52 ETPs have enriched interactions with JAG1 as they migrate away from the CMJ, suggesting increased JAG1 interactions could skew ETP lineage commitment toward less inflammatory DC phenotypes (Figure 6). In the female cortex, we observe increased cTEC and class II+ DP interactions and increased interactions between cortical DC and positive selection niches, suggesting thymocyte self-selection may play a larger role during positive selection (Figure 6). Conversely, the female medulla shows decreased inflammatory pathway activation and fewer medullary cells. These data suggest females prioritize generating a larger repertoire of DPs over deleting autoreactive cells through negative selection, potentially contributing to sex differences in autoimmune disease prevalence in females.96

In males, we observe enriched DLL4 interactions with ETPs, which aligns with previous data demonstrating that androgen levels positively correlate with DLL4 on cTECs.29 The male cortex shows increased interactions with mature CD3+ DPs and cTECs, suggesting male thymocytes may have lower proliferation rates post β-selection, allowing sufficient space for positive selection. In the medulla, male-activated mTECs exhibit increased inflammatory pathway markers, and male Tregs exhibit higher inflammatory modulation and activate thymic involution pathways.75 Upregulation of inflammatory modulation by male rrTregs may regulate the higher proinflammatory signaling in male cells (Figure 6). Interestingly, post-pubertal males have more Tregs and fewer CD4 T cells than females, possibly due to a more inflammatory medullary environment skewing CD4 development toward the Treg lineage.31

We further explore sex differences in thymus size control mechanisms. Among fibroblast populations, we find significant differences in expression of growth and angiogenesis factors, such as VEGFA and FGFs, potentially contributing to the size difference in male and female thymuses at this age (Figure 6). These data align with and extend known sex differences in growth factor expression, including sex-biased expression of growth hormone and IGF-1 in regulating size of different tissues.97,98 Importantly, these results indicate sex-specific differences in early thymus structure maintenance and growth, which could skew T cell development. We also establish an early transition toward an adipogenic environment in males. These observations align with findings in model organisms, where young male rats exhibit higher rates of thymic involution52 and early postnatal male primates have a larger interlobular fat area.26 Together, these factors define two possible mechanisms contributing to a male-female difference in thymus size and involution kinetics.

Future studies should test how sex differences at the transcript, niche, and organ level impact differential T cell production and quality as well as explore how sex differences in other organs contribute to known differences in immune responses. Defined in vitro and organoid culture systems replicating the thymic microenvironment present powerful platforms to test if the cell type-specific and sex-specific differences identified here lead to increased autoimmune disease incidence among females and increased infection susceptibility in males. Furthermore, given the surprising sex-based differences at this early postnatal stage, future work should examine aged thymus to investigate how cellular level differences in thymic involution kinetics may translate to larger impacts on our immune system later in life.

Limitations of the study

Our analysis of intra-sex variation is limited by access to patient samples as well as the inability to conduct mechanistic experiments in the context of a whole organism. There is an opportunity for future work to further validate and expand on predicted ligand-receptor interactions.

The thymic epithelium is responsible for the secretion of thymic peptides, which intervene in some steps of intra- and extrathymic T cell differentiation. Recent data suggest that thymic hormone secretion is modulated by the neuroendocrine network, comprising thyroid, adrenals, and gonads. However, the role of the pituitary gland in this regulation is still poorly understood. In the present paper we studied the in vivo and in vitro influences of PRL on the secretion of thymulin, one of the chemically defined thymic hormones, by thymic epithelial cells (TEC). When injected daily (20-100 micrograms/20 g) in young or old C57BL/6 mice, PRL induced a specific increase in thymulin synthesis and secretion, respectively, measured by the number of thymulin-producing cells in the thymus and the peripheral levels of the hormone. This stimulation was dose dependent and reversible after the end of treatment. Similar findings have been made in animals with pituitary dwarfism, known to have low levels of circulating thymulin. This stimulatory effect was also observed in primary cultures of human and mouse TEC when PRL (10(-7) to 10(-8) M) was applied to culture supernatants, thus suggesting that PRL could act directly on TEC. In addition, we induced in vivo experimental hypoprolactinemia, treating mice with bromocriptine, a dopamine receptor agonist that inhibits pituitary PRL secretion. Bromocriptine treatment (100-200 micrograms/20 g) yielded a significant decrease in thymulin secretion that could be reversed by coincident treatment with PRL. In the light of previous observations that bovine GH can also increase thymulin production in aged dogs, we performed a series of experiments in vitro to evaluate whether GH has a direct effect on TEC. We observed that only human GH preparations that are known to have a PRL-like effect were efficient in stimulating thymulin biosynthesis and release into the culture supernatants. The effects of PRL on TEC were not restricted to thymic hormone production. We observed that TEC proliferation, as well as the numbers of a TEC subset defined by the expression of cytokeratins 3 and 10, could also be increased by PRL treatment. All these findings show that the pituitary gland directly affects TEC in terms of cytoskeletal and secretory protein expression as well as cell cycle.. This paper reviews the mechanism of sex hormone actions on the thymus, presenting mainly our data obtained at the cellular and molecular levels. First, data supporting the "genomic" action via the nuclear sex hormone receptor complexes are as follows: 1) sex hormone receptors and the thymic factor (thymulin) are co-localized in thymic epithelial cells, but not in T cells; 2) production/expression of thymic factors (thymulin, thymosin alpha 1) are remarkably inhibited by sex hormone treatment; 3) sex hormones cause changes in T cell subpopulations in the thymus; and 4) sex hormones strongly influence the development of thymus tumors in spontaneous thymoma BUF/Mna rats through their receptor within the tumor cells. Secondly, data indicating the "non-genomic" action of sex hormones via a membrane signal-generating mechanism are as follows: 1) the proliferation/maturation of thymic epithelial cells is mediated through protein kinase C activity introduced by sex hormones; 2) sex hormones directly influence DNA synthesis and cdc2 kinase (cell cycle-promoting factor) activity..

pubmed.ncbi.nlm.nih.gov/2737149/

www.cell.com/developmental-cell/fulltext/S1534-5807(24)00539-2

I'd wanted them for a couple of years, and finally I found a local source for PURPLE LED fairy (faerie? feri?? no.) lights, and hooboy was I happy! Yay! Purple LED lights, no shipping! As soon as I got home I strung them up.

But- wait! I know one or two things about semiconductor physics and engineering -- and there's NO SUCH THING as a purple LED! What's going on?!

Al Centro DINO CAMPANA non si scherza.. e si spazia anche sul SANITARIO……Donne in primo piano.. ed i Progressi della ONCOLOGIA

Stefano Tamberi

Professore a contratto a titolo gratuito

Scuola di Medicina e Chirurgia

Curriculum Vitae

Nato il 26 giugno 1967, ha conseguito la laurea in Medicina e Chirurgia nel 1992 con 110 e lode presso L'Università di Bologna. Nel 1997 si è specializzato in Oncologia con 70 e lode presso l'Università di Bologna e consegue nel 2001 il dottorato di ricerca in Oncologia Gastrointestinale presso l'Università di Modena e Reggio Emilia. Vincitore dei premi "E.Baroni" e "Evaristo Stefanelli" per la ricerca in oncologia presso l'Università di Bologna negli A.A 1997 e 1998. Dal 2010 è direttore dell'UO di Oncologia dell'Ospedale di Faenza.

Le principali aree di ricerca clinica oncologica sono state nel corso degli anni la patologia oncologica polmonare, gastrointestinale e ginecologica. Membro attivo dei principali gruppi di ricerca nazionali e internazionali di tali ambiti (Gruppo MITO, Gynecologic cancer tergroup, GISCAD etc) è stato principal investigator di numerosi studi internazionali sui tumori dell'ovaio, del polmone e dei tumori del colon.

Ha sviluppato negli ultimi anni un interesse particolare perl'approccio psico-sociale al paziente oncologico con un periodo di visita presso le principali istituzioni del Quebec (Canada) per lo sviluppo di un processo organizzativo di cure oncologiche centrate sul paziente. Ha sviluppato progetti di supporto clinico psiconcologico a pazienti affette da carcinoma mammario operato con l'istituzione di supporto psicologico di gruppo e la consulenza psicologica prevista nella quotidiana attività clinica. Tali progetti pilota sono stai presentati nell'ambito del progetto "Empatia" della Regione Emilia Romagna (RER). Ha partecipato al corso regionale sulla "Health Literacy" tenuto dalla Prof.ssa Rudd (Harvard - Boston) e ha sviluppato progetti innovativi di comunicazione nel personale medico e infermieristico da lui diretto.

Alcune sue Pubblicazioni

1. Carboplatin, Fluorouracil and L-Folinic Acid in the treatment of Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN) . Guaraldi M., Martoni A., Morelli F., Panetta A., Tamberi S., Pannuti F. Annals of Oncology 5 (suppl.8):123,1994

2. A phase I-II study on 5-day 5-Fluorouracil continuous infusion with levo-Folinic Acid modulation in advanced colo-rectal cancer. Martoni A., Angelelli B., Panetta A., Tamberi S., Pannuti F. Proceedings of the "XVI International Cancer Congress". New Delhi 30 ottobre-5 novembre 1994

3. Combined chemo-immuno-ormonotherapy of advanced renal cell carcinoma. Panetta A., Martoni A., Guaraldi M., Tamberi S., Casadio M., Lelli G., Pannuti F. Journal of Chemotherapy 6:5,349-353, 1994

4. Prevalenza e caratteristiche morfologiche di lesioni polipoidi del tratto digestivo superiore nella poliposi adenomatosa familiare. Santucci R., Volpe L., Calabrese C., Poggi B., Di Febo G., Tamberi S., Biasco G. "I Tumori gastrici. Bilanci e prospettive" Roma 9-11 novembre 1995

5. Terapia cronomodulata dei tumori solidi. Biasco G., Brandi G., Tamberi S. G.Biasco. "Trials clinici in oncologia". Bologna, 1995

6. Abnormal mucosal cell proliferation as a biomarker of gastrointestinal cancer: methodological issues and clinical applications Biasco G., G.M.Paganelli, U.Zannoni, G.Brandi, R.Santucci, M.Renga, P.Mordenti, S.Tamberi, L.Barbara. Journal of tumor marker oncology vol.10 ,2, pag.89, 1995

Drone Ranger : 4 Oscillators, 2 white noise sources, 2 ring mod, 2 Fuzz, 2 resonant low pass filters with LFO modulation.

Ahhh - campus Brutalism! As previously discussed, the tough-looking, severe and opaque concrete-and-masonry designs that popped up all over American campuses in the late 1960s aren't always reducible to the tidiest narrative at hand - that they were intended to armor the institution against its increasingly vocal critics in a time of social ferment. I'm generally not opposed to these readings outright, but they almost always need at least a little modulation. The timeline at Oberlin's Mudd building (with a design secured in 1967) seems pretty close to the mark, but you have to square fears of rebellious students with the way the building is actually described in the marvelous orange period piece that is its dedication volume. While obviously this stresses the college's own view of things, it opens with the architects' own statement, which places the thing squarely in the oft-overlooked comfy-cozy-friendly Brutalist discourse. The goal is to produce an "informal atmosphere" for study, with "organized nooks and crannies," to "fit a variety of moods and feelings." This granola sensibility, strongly reminiscent of Herman Hertzberger, suggests also a likely borrowing from Kahn's view of a building as a "harboring thing."

Sadly, we didn't have time to really explore this one - it seems the modest double-height space is on the piano nobile, and the bridges over the entry (which a critic might read as foreboding archers' redoubts) are meant to shelter the entry while providing honors students with removed study carrels (and what must be lovely views of the quad). The first step in meeting Brutalism head-on is accepting that, for the architects if not the users, the apparent contradiction between severe abstraction and day-glo floppy furniture in which to "rap" about the issues of the day was not a contradiction. These were supposed to be the communal buildings of the future; they were visually abstract and massed according to internal space concepts in order that the open-minded youth of the 1970s would feel at home in them. While it's a commonplace to assume that everybody in fact found them menacing and alienating, I for one always felt more comfortable, as a student, in the nook-and-cranny buildings than the overscaled gable-and-column fests that came later. That's not to say that I think this thing needs to be quite so huddled and dark, or that its monumental glowering presence doesn't perhaps serve (or produce) a certain top-down relationship between institution and user. But the fit is always loose.

Jamis DXT Dual Sport Bicycles ON/OFF road hybrids: What are they? This is a hybrid with a mountain bike position but with road wheel 29” 700c wheels that are a bit wider then road hybrids so they are great for all round use: roads, dirt roads, a bit of mud as well. You can put wider tires with bigger tread as well if you want to go hard core off roading. They also have suspension forks and mountain bike gears so they are like a light weight fast mountain bike.

The dual-sport DXT’s are pumped-up, go-anywhere/do-anything versions of our Allegro fitness bikes. With more gearing range to take on steeper hills and tougher terrain. Wider tires with a trail-capable tread for access to more riding areas, both paved and packed. And disc brakes and suspension forks for real off-road exploration and off-pavement adventure.

Fast Tires: The advantage of large diameter wheels is getting a lot of press these days with all the noise and news about 29’er mountain bikes. We like to think that the DXT is one of the original 29’ers. With big 700c hoops (same as a 29’er) that roll over bumps & holes better than smaller diameter 26” or 27.5” wheels, and with a bigger contact patch for greater traction and control. But in the case of the DXT, with a smaller 40c width & smoother tread that significantly reduces rolling resistance over fatter, knobbier mountain bike tires for faster sailing on streets and paths.

Absolute versatility: Every DXT offers a full complement of eyelets and rack mounts to simplify installation of carriers and fenders. We even include bosses on the underside of the seatstays for installation of a ring lock. Ring locks are tremendously popular in Europe. A simple turn of the key immobilizes the rear wheel and prevents someone from riding off with your bike.

Go Anywhere. Do Anything: The drivetrains on our DXT bikes feature long cage ATB rear derailleurs, full-size triple chainring cranksets and big 11-34 or 32T cassette blocks. This gives you the dual advantage of having high road bike gearing for controlled pedaling at speed on descents and low mountain bike gearing for easier pedaling uphill.

Full Shimano Shift Systems: Fully integrated shifting systems offer the most precise and reliable performance. That’s why every DXT offers Shimano shifters, Shimano front and rear derailleurs, Shimano cranksets and Shimano cassettes.

Awesome brakes: The advantages of disc brakes over rim brakes on a versatile bike like the DXT far exceed their sole disadvantage, weight gain. Besides their incredible power and modulation, they’re just plain safer, especially in the rain. Once rims get wet or muddy, using friction to stop the wheel at its circumference is less efficient than using friction to stop a less wet or muddy small diameter disc near the center of the wheel from rotating. And eliminating the rim from braking surface duties results in a longer lasting wheel

Suspension When you need it, Lock out when you don’t: The advantage of a suspension fork should be intuitively clear: hit a bump and absorb it. Hit a bump and stay in control of your bike. But suspension isn’t always desirable. When riding on smooth pavement or climbing, pedaling energy and power can be absorbed and dissipated by the movement (bobbing) of the fork. Enter lockout. With a flip of a knob on the top of the fork, the fork’s travel can be locked from movement, allowing the bike to be 100% responsive to pedaling input .

Adjustable Cockpit height (stem adjustment): Proper fit on your bike is critical for maximum performance and comfort. That’s why we offer the patented ATS adjustable threadless steering system on the Allegro Elite and Comp models. Whether you want to fine tune your ride and establish the perfect fit, or change it regularly to suit different terrain, with this stem, adjusting your handlebar height is as easy as adjusting your seat post height. You can even adjust it quickly while out on a ride.

2016 DXT Sport $586 WAS $853

www.rbinc-sports.com/catalog/bikes/jamis-bikes/street/dua...

2015 DXT SPORT STEP THROUGH $599 WAS $955

www.rbinc-sports.com/catalog/bikes/jamis-bikes/street/dua...

2015 DXT COMP $817 WAS $1279

www.rbinc-sports.com/catalog/bikes/jamis-bikes/street/dua...

2016 DXT COMP $699 WAS $1069

www.rbinc-sports.com/catalog/bikes/jamis-bikes/street/dua...

2016 DXT ELITE $899 WAS $1459

www.rbinc-sports.com/catalog/bikes/jamis-bikes/street/dua...

2017 DXT SPORT $771

www.rbinc-sports.com/catalog/bikes/jamis-bikes/street/dua...

2017 DXT SPORT FEMME $771

www.rbinc-sports.com/catalog/bikes/jamis-bikes/street/dua...

www.rbinc-sports.com/catalog/bikes/jamis-bikes/street/dua...

www.rbinc-sports.com/jamis-factory-outlet-store/jamis-dxt...

My only synth for the night, the excellent Nord Lead 3. It has a wooden pitch bend lever and stone modulation wheel! Seriously!

Intension - I wanted to capture the beautiful flowers at Franklin park.

referencing reading - freeman states removing the quality of color from an image enhance its other qualities. With the modulation entirely in tone, the eye pays more attention to texture, line, and shape.

edits - converted the image to black and white, added more contrast, increased the yellows/greens. cropped the image.

(L - R) Jason Lowery (graduate student), Elizabeth Sztul (PI), Jahn Wright (graduate student), Paulina Wyrozumska (post-doc), Jay Bhatt (graduate student),

Eunjoo Lee (research assistant).

The Sztul lab "aims to understand how cells deliver proteins to their surface and develop a “virtual” time and space map of the molecular events that regulate protein movement. The ultimate goal of our studies is to provide a detailed molecular understanding of protein traffic as the basis for the development of disease-specific therapies. Currently we are using our expertise in membrane trafficking to address two specific questions: (1) modulation of glucose transporters trafficking independent of insulin and (2) to induce apoptosis of cancer cells by inhibiting ER-Golgi traffic."

This jazz waltz features vocal, saxophone, and flute performances accompanied by a jazz trio.

Vocal - Lee Fitzsimmons * Live Yamaha tenor saxophone (YTS - 21) - Lee Fitzsimmons * Live Gemeinhardt flute - Lee Fitzsimmons

Piano - Lee Fitzsimmons * Acoustic bass - Lee Fitzsimmons * Drum kit and ride cymbals - Lee Fitzsimmons

LYRICS

"Think I'm gonna go sail away, forever and a day. Through the clouds and over the trees, think I'm gonna go sail away.

Gonna get me a big balloon, so I can fly away to the moon. Through the stars on Mercury's tune, gonna get me a big balloon...

Breathe deep the golden air, swirling through our minds. We'll find a solace there, an essence so sublime."

"Maybe we could fly away to Mars, the whole universe is ours. See the light wherever we are, maybe we could fly away to Mars.

Jupiter and Venus, too. That's what I'm really gonna do. Saturn in it's hazy dew, Jupiter and Venus, too...

Breathe deep the golden air, swirling through our minds. We'll find a solace there, an essence so sublime."

The jazz trio sets up a spirited groove; the vocal begins. A soulful tenor saxophone fills the gaps of the vocal melody during the verses. In the chorus, a playful flute plays during the vocal breaks as a clever modulation occurs. After the chorus, the saxophone takes a lively be-bop style ride and is then joined by the flute, so the pair can present a two part harmony that sets the stage for the second verse. The entire form repeats and the song ends on the final note of a brief coda.

The philosophical essence of this tune is the concept of "floatation" as an allegory for the ascent of the kundalini energies up the spinal cord. The planetary chakras of alchemical lore are mentioned in the lyrics as guiding beacons of light that guarantee that the balloon's pilot is never lost. The golden air of the chorus is symbolic of the heliosphere that permeates all of the solar system that lets all of the inhabitants of its golden realms know that they are never alone.

This "essence so sublime" is the true solace of Sol.

Noto

⚫️

Book :

Christian Marclay

Shuffle

Aperture

2007

CD :

Random Industries

Selected Random Works

Ritornell

RIT15

Design . Angela Lorenz

'You may play this CD on a random / shuffle position

on your CD player.'

Sebastian Meissner

iMusic :

Cavern Of Anti - Matter

Phase Modulation Shuffle

Duophonic

DUHF38

MGA ...

Preset controls. For those unfamiliar with 405 line sets, the "Limiter" control is used to limit peak white during periods of electrical interference. This is because with the positive modulation system, peak white is the same polarity as interference pulses. Not limiting the peak white can result in defocussing as the EHT current is increased beyond normal.

Space Baby modulated beat-synced digital delay, available at woosteraudio.com/space-baby.html

amplitude modulation of an RF carrier with 4000-series chips

Luise Rainer was the daughter of Heinrich and Emilie (née Königsberger) Rainer. Luise was born in Düsseldorf, Germany and raised in Hamburg and later in Vienna ,Austria.

Her father was a businessman who settled in Europe after spending most of his childhood in Texas, where he was sent at the age of six as an orphan. (Luise has stated that because of her father, she is an American citizen "by birth".) Luise family was upper-class and Jewish.

She was only six when she decided to become part of the entertainment world, and recalled being inspired by watching a circus act:

At age 16, Luise chose to follow her dream to become an actress; under the pretext of visiting her mother, she travelled to Düsseldorf for a prearranged audition at the Dumont Theater. She later began studying acting with Max Reinhardt, and, by the time she was 18, there was already an "army of critics" who felt that she had unusual talent for a young actress. She soon became a distinguished Berlin stage actress as a member of Reinhardt's Vienna theatre ensemble. Her first stage appearance was at the Dumont Theatre in 1928, followed by other appearances, including Jacques Deval's play 'Mademoiselle', Kingsley's 'Men in White', George Bernard Shaw's 'Saint Joan', 'Measure for Measure', and Pirandello's 'Six Characters in Search of an Author'.

In 1934, after appearing in several German language films, she was seen performing in the play 'Six Characters in Search of an Author' by MGM talent scout Phil Berg, who offered her a three-year contract in Hollywood. He thought she would appeal to the same audience as Swedish MGM star Greta Garbo. Initially, Luise had no interest in films, saying in a 1935 interview: "I never wanted to film. I was only for the theatre. Then I saw 'A Farewell to Arms' and right away I wanted to film. It was so beautiful.

Luise moved to Hollywood in 1935 as a hopeful new star. MGM studio head Louis and story editor Samuel Marx had seen footage of Luise before she came to Hollywood, and both felt she had the looks, charm, and especially a "certain tender vulnerability" that Mayer admired in female stars. Because of her poor command of English, Mayer assigned actress Constance Collier to train her in correct speech and dramatic modulation, and Luises English improved rapidly.

Her first film role in Hollywood was in 'Escapade' (1935), a remake of one of her Austrian films, co-starring William Powell. She received the part after Myrna Loy gave up her role halfway through filming. After seeing the preview, Luise ran out of the cinema displeased with how she appeared, stating: "On the screen, I looked so big and full of face, it was awful. The film generated immense publicity for Luise, who was hailed as "Hollywood's next sensation.

Her next performance was as the real-life character Anna Held in the musical biography 'The Great Ziegfeld', again co-starring William Powell. Powell, who was already impressed by Luise acting skill, had earlier given her equal billing in 'Escapade'. Studio head Mayer did not want her playing the part, seeing it as too small: "You are a star now and can't do it," he insisted. Shortly after shooting began in late 1935, doubts of Luis's ability to pull off the role emerged in the press. She was criticized for not resembling the Polish-born stage performer. The director admitted that the main reason Luise was cast was her eyes, claiming that they "are just as large, just as lustrous, and contain the same tantalizing quality of pseudo naughtiness" the part required.

As Thalberg expected, she successfully expressed the "coquettishness, wide-eyed charm, and vulnerability" required. Luise so impressed audiences with one highly emotional scene, that she received the Academy Award for Best Actress. In one scene, for example, her character is speaking to her ex-husband Florenz Ziegfeld over the telephone, attempting to congratulate him on his new marriage: The camera records her agitation; Ziegfeld hears a voice that hovers between false gaiety and despair; when she hangs up she dissolves into tears.

Luise next film was 'The Good Earth' (1937), in which she co-starred with Paul Muni; she had been picked as the most likely choice for the female lead in September 1935. The role, however, was completely the opposite of her Anna Held character, as she was required to portray a humble Chinese peasant subservient to her husband and speaking little during the entire film. Her comparative muteness, was "an astounding tour de force after her hysterically chattering telephone scene in 'The Great Ziegfeld', and contributed to her winning her second Best Actress Oscar.

The award made her the first actress to win two consecutive Oscars, a feat not matched until Katharine Hepburn's two wins thirty years later.

In late 1936, MGM conceived a script called 'Maiden Voyage' especially for Luise. The project was shelved and eventually released as 'Bridal Suite' in 1939, starring Annabella as 'Luise'. Another 1936 unrealised film project that involved Luise was 'Adventure for Three', which would have co-starred William Powell. In 1938, she played Johann Strauss's long-suffering wife Poldi in the successful Oscar-winning MGM musical biopic 'The Great Waltz', her last big hit.

Most critics agreed Luise was "at her most appealing" in 'The Toy Wife'. The final MGM film Luise made was 'Dramatic School'. At the time she was cast in the film, her box office popularity had declined considerably, and she was one of the many well-known stars—along with MGM colleagues Greta Garbo, Joan Crawford, and Norma Shearer, and Katharine Hepburn, Mae West, Fred Astaire, Kay Francis and others—dubbed "Box Office Poison" by the Independent Theatre Owners of America.

Luise refused to be stereotyped or to knuckle under to the studio system, and studio head Mayer was unsympathetic to her demands for serious roles. Furthermore, she began to fight for a higher salary, and was reported as being difficult and temperamental. Thereby, she missed out on several roles, including the female lead in the Edward G. Robinson gangster film 'The Last Gangster' (1937), losing out to another Viennese actress, Rose Stradner. Speaking of Mayer decades later, Luise recalled, "He said, 'We made you and we are going to destroy you.' Well, he tried his best." Luise made her final film appearance for MGM in 1938 and abandoned the film industry.

She travelled to Europe, where she helped get aid to children who were victims of the Spanish Civil War. Nevertheless, she was not released from her contract and, by 1940, she was still bound to make one more film for the studio. Disenchanted with Hollywood, where she later said it was impossible to have an intellectual conversation, she moved to New York City in 1940 to live with playwright Clifford Odets, whom she had married in 1937. Luise had never made it a secret that she felt terrible as Odets' wife. She filed for divorce in mid-1938, but proceedings were delayed "to next October" when Odets went to England. The divorce was finalized on May 14, 1940.

While in Europe, Luise studied medicine and explained she loved being accepted as "just another student", rather than as a screen actress. She returned to the stage and made her first appearance at the Palace Theatre, Manchester, on May 1, 1939, as Françoise in Jacques Deval's play 'Behold the Bride'; she played the same part in her London debut at the Shaftsbury Theatre on May 23, 1939. Returning to America, she played the leading part in George Bernard Shaw's 'Saint Joan' on March 10, 1940, at the Belasco Theatre in Washington, D.C. under the direction of German emigrant director Erwin Piscator. She made her first appearance on the New York stage at the Music Box Theatre in May 1942 as Miss Thing in J. M. Barrie's 'A Kiss for Cinderella.

She made an appearance in 'Hostages' in 1943 and abandoned film making in 1944 after marrying publisher Robert Knittel. Luise took her oath of allegiance to the United States in the 1940s, but she and Knittel lived in the UK and Switzerland for most of their marriage. Robert Knittel died in 1989. Luise resided in Eaton Square, London, in an apartment in the same building once inhabited by film star Vivian Leigh, also a two-time Oscar winner. The couple had one daughter, Francesca Knittel, now known as Francesca Knittel-Bowyer.

Luise died on December 30, 2014, in London at the age of 104 from pneumonia. She was two weeks shy of her 105th birthday.

Edificio: Centro de Estudios Hidrográficos (vista interior de la cubierta)

Arquitecto: Miguel Fisac

Año: 1960

Lugar: Madrid

Orange Juice Drive is in a classical RAT type circuit and sounding topolgy. We add extra switch for select between symmetric or asymmetric clipping. Not operable with battery.

www.customanalogpedals.com/orange-juice-drive/

Quick Overview

This wireless adapter can be worked with laptops, notebooks and PC desktop computer as well. Just plug and enjoy Internet.

Online at www.ipcaccessories.com/300mbps-usb-wireless-adapter-wifi-...

Product Description

Features:

802.11n/g/b 300M Wireless WiFi USB 2.0 Adapter (Realtek 8191 Chipset).

Complies with IEEE 802.11n(draft), IEEE 802.11g, IEEE 802.11b standards.

Provides USB 2.0/1.1 hight speed interface.

Transmission rate up to 300Mbps.

Supports Ad-Hoc, infrastructure WLAN network, wireless roaming.

Supports Windows 2000, XP 32/64-bit, Vista 32/64-bit, Linux, MAC OS x.

With an external antenna.

Simple configuration and easy to use.

It can be worked with laptops, notebooks and PC desktop computer as well.

Specifications:

Wireless standards: IEEE 802.11n(draft), IEEE 802.11g, IEEE 802.11b standards

Interface: hight speed USB 2.0/1.1

Data rate:

802.11n up to 300M (downlink) and 150M (uplink);

802.11g 54/48/36/24/18/12/9/6 Mbps auto fallback;

802.11b 11/5.5/2/1 Mbps auto fallback.

Frequency range: 2.4GHz ISM

Chipset: Realtek 8191

RF frequency: 2412-2462Mhz (North America); 2412-2472Mhz (Europe); 2412-2484Mhz (Japan)

RF output power: 13-17dBm

Radio channel: 1-14 channels

Range coverage: up to 3 times farther range than 802.11g

Roaming: full mobility and seamless roaming from cell to cell

Modulation: 11n BPSK QPSK 16QAM 64QAM OFDM; 11g BPSK QPSK 16QAM 64QAM OFDM; 11b DQPSK DBPSK DSSS CCK

Data security: 64/128-bit WEP Encryption WPA, WPA-PSK, WPA2-PSK, TKIP/AES

Media access control: CSMA/CA with ACK

LED indicator: link/active (green)

Operating system: Windows 2000, XP 32/64-bit, Vista 32/64-bit, Linux, MAC OS x

Color: black

Antenna length: 11cm

Item size: 7*2.5*1.2cm

Item weight: 22g

Package size: 17.5*11*1.5cm

Package weight: 50g

Package including:

1 * Wireless USB Adapter

1 * Software CD

Taken of the 1st Year Radio project showing the components of an AM radio, has not been altered in any way.

Networked Fabrication for Urban Provocations.

Shifting Paradigms from Mass Production to Mass Customization

Computational architecture and design course

amorphica.com/networked.html

www.facebook.com/amorphica

Conventional construction methods all depart from the basic premises of mass production: standardization, modulation and a production line. What these systems developed during the last two centuries fail to take into account are the evolutionary leaps and bounds the manufacturing industry has taken over the last decades. With the introduction of CNC technologies and rapid prototyping machines have altered the paradigms of fabrication forever. It is due to these new tools that it is now possible to create (n) amount of completely unique and different pieces with the same amount of energy and material that is required to create (n) identical pieces. The possibilities for implementation of new forms, textures, materials and languages are infinite due to the versatility that these new tools offer a growing network of architects, designers, fabricators that are integrating them into their professional practices to generate unique and precise objects that respond to countless data and real-life conditions.

Instructors:

Monika Wittig [ LaN, IaaC ]

Shane Salisbury [ LaN, IaaC ]

Filippo Moroni [ SOLIDO, Politecnico di Milano ]

MS Josh Updyke [ Advanced Manufacturing Institute, KSU, Protei ]

Aaron Gutiérrez Cortes [ Amorphica ]

Xung PWM là cụm từ viết tắt của Pulse Width Modulation, giải nghĩa hiểu đơn giản thì xung PWM là một loại tín hiệu được ứng dụng trong vật lý để điều chỉnh điện áp tải ra của các thiết bị điện tử, thiết bị điện dựa trên sự thay đổi về độ rộng của chuỗi xung vuông, điều này dẫn đến sự thay đổi điện áp ra.

Các PWM khi biến đổi sẽ có cùng 1 tần số và khác nhau về độ rộng của sườn dương hay sườn âm.

👉Tham khảo thêm bài viết sau đây để rõ hơn.

shadow.vn/pwm-la-gi-va-anh-huong-den-den-pin-nhu-the-nao

SHADOW Việt Nam - Chuyên cung cấp đèn pin cao cấp, đèn pin nhập khẩu chính hãng

Add: Số 51A Phan Kế Bính, phường Cống Vị, quận Ba Đình, Hà Nội

SĐT: 0934883366

TIN: 0108618521

--------------------------------

Các trang mạng xã hội khác của Shadow Việt Nam:

dribbble.com/shots/19683553-Xung-PWM-l-g-r-ng-xung-nh-h-n...

ko-fi.com/i/IH2H2FS9HG

linkhay.com/blog/390918/xung-pwm-la-gi-do-rong-xung-anh-h...

gab.com/denpinshadowvn/posts/109192745018126417

shadowvietnam.blogspot.com/2022/10/pwm-la-gi.html

Use this mind-map to improve your presentation skills.

Dub~Step~Arcade Controls

01~ Steps (amount of steps in the tone)

02~ Mod Depth (amount of modulation of the pitch)

03~ LFO - Square or Triangle select for modulation depth

04~ A/D or LFO select for modulation depth

05~ Pitch (manual oscillator pitch setting)

06~ VCA level (volume)

07~ Manual or A/D generator select for VCA

08~ Attack control (how long the A/D gen takes to get to max amount)

09~ Decay (how quickly the A/D voltage drops)

10~ Repeat on /off (A/D generator automatically repeats at the end of each cycle)

11~ FIRE! starts the A/D sequence

12~ LFO speed with flashing indicator

KITS AVAILABLE MAY 2010 FROM

www.magicmess.co.uk/DSA/dsa.php

Well do we have news for you… (:-D

Resulting from my bro, Maxsimus, latest visit to Singapore this week and the photo shoot we set up during his stay, we decided jointly to look into PP.. issues and take matters seriously... (:D into our own hands “so to speak” and create our very own processing approach that we have named : “Hallucinogeneric”.

Based on the saturation of lens “Aperture Mode Locking” AML and the self-amplitude “Time modulation coefficient” or TMC, Our work deals with the saturation of the lens Aperture mode locking mechanism. A quantitative description of TMC and the self-amplitude modulation effect in a laser cavity can be derived. Considering both the nonlinear and geometrical (curvature vector or CV) differences between lenses and camera sensors (full frame or not) we concluded that the “CV” differential relationship between cameras and lenses results in nonlinear light modulation.

The loss of the “Light Pulse Conformation Strength” or (LPCS) in a cavity due to “bleaching or excess or lack of light” creates a “Fast Saturation Absorbency” or FSA behavior of any type of camera and lens combination all together. The “Intracavity Aperture Factor” or IAF specific to a given lens type produces the appearance of “FLICKERING” or image instabilities. Our goal was then to elaborate a formidable yet simple approach that allows the prediction of “FLICKERING” or image instabilities, and develop a post processing technique or method that can be as useful for short pulse laser cavity design in general than it is compared to a mouse pad - mouse relationship.

The obtained “Self-Amplitude Coefficient” or SAC is included within the TMC to which LPCS and FSA are added to give a ray-pulse matrix formalism, and a simple model for the temporal pulse parameters regarding only the self amplitude “Time Modulation Coefficient” or TMC can then be solve via a simple quadratic differential integration (Patent pending).

This new “Hallucinogeneric” model sets a limit for the maximum pulse light energy of a stable solution for a given nonlinear modulation and “Camera Lens Combination” or CLC.

Our “Hallucinogeneric” post processing technique we are certain will soon become the newest and most revolutionary PP faved method yet we are certain. We simply baptized “ this new processing technique Lens Setting Dynamics” or “L.S.D.” (:D allows us not only to take night shots in broad daylight, but also gives us a stunning doubled and colored vision extremely useful for reflective photography. Combined with “ Hallucinogeneric” TM you are bound to see all sorts of colors in all sorts of way.

The above is the second of a series relating to this amazing Field and post-processing breakthrough.

To know more, thank you for sending your questions and donations to Maxsie & I at Wetakecash@ourbankaccount.com or wtc@ourbankaccount.com

D. Maxsie – D. Phil

P.S.: "caution applies as D. may stand for delusional." A. Einstein

Best seen in Large. Thanks.

350 bed dormitory, dining hall, auditorium, shared facilities

195,000 GSF

Completed 2002

2003 National AIA Design Award

2002 New York AIA Design Award

2000 Progressive Architecture Award

AW36-20 picture tube. It has a bent gun and ion trap but electrostatic focussing.

12 Interlocking Irregular Hyperboloidal Dodecahedra 360 units

In my hand.

Following an initial prototype with only a singular unit type which attempted a hexahedral symmetry analog of 30 Dodecahedra, I developed this more nuanced version, which has a different exterior weaving pattern and multiple paper proportions. However, as a constraint, I attempted to use only one pocket type for all of the units. This makes some vertices different than others in terms of the dihedral angles of the surrounding units, but the edges shafts are long enough to accommodate modulation between vertices without appreciable difficulty in most cases. This is constructed via scaffolding so that each dodecahedron represents one edge of a cube. The resulting compound is at the time of writing this, the largest interlocking origami cubic symmetry wireframe compound by unit count that I know of.

Designed by me.

Folded out of Cordenons’ Stardream paper.

Canyon de Chelly, Arizona

Berkeley, CA

with the little Minimoog plaque peeled-off.

Designed by Robert Moog in 1970, the Minimoog Model D synthesizer is still regarded as the Rolls Royce equivalent for analog keyboard-based synthesizers. Specifically designed for touring musicians, the minimoog exported electronic music experiments from university labs out to the masses - and her deep farting bass-sounds (think of Kraftwerk's Autobahn), lead and space bleeps and sweeps have become HUGELY popular over the last 38 years.

There were originally 13,000 minimoogs produced between 1970 and 1981. After a brief hiatus during the digital-synth craze in the 1980s, the minimoog enjoyed a resurgence of interest among musicians since the 1990s...and yes, it's becoming harder to get a hold on one.

I obtained this Mini from a studio garage sale back in 1989 for US$ 150 (in prime condition - save the crackling external input knob). After lying dormant for 7 years now, it's time to bring life back into this 1973 model D mini. Tropical humidity heavily damaged the furnishing. It needs re-tuning of the oscillators, cleaning of the electronic board, new switches for filter modulation, and thinking about a new base panel.

How to control the intensity of some LEDs in PWM (Pulse Width Modulation).

/*

Fade

This example shows how to fade two LEDs on pin 9 and pin 10

using the analogWrite() function.

The analogWrite() function uses PWM, so if

you want to change the pin you're using, be

sure to use another PWM capable pin. On most

Arduino, the PWM pins are identified with

a "~" sign, like ~3, ~5, ~6, ~9, ~10 and ~11.

This example code is in the public domain.

*/

int led1 = 9; // the PWM pin the LED is attached to

int led2 = 10;

int brightness = 0; // how bright the LED is

int fadeAmount = 5; // how many points to fade the LED by

// the setup routine runs once when you press reset:

void setup() {

// declare pin 9 and 10 to be an output:

pinMode(led1, OUTPUT);

pinMode(led2, OUTPUT);

}

// the loop routine runs over and over again forever:

void loop() {

// set the brightness of pin 9:

analogWrite(led1, brightness);

analogWrite(led2, brightness);

// change the brightness for next time through the loop:

brightness = brightness + fadeAmount;

// reverse the direction of the fading at the ends of the fade:

if (brightness = 255) {

fadeAmount = -fadeAmount;

}

// wait for 30 milliseconds to see the dimming effect

delay(30);

}

amorphica.com/networked.html

Group 4_

Aaron Onchi, Betty Sanchez, Roberto Gutierrez, Frank Durán , Belén Olaya García

Networked Fabrication for Urban Provocations.

Shifting Paradigms from Mass Production to Mass Customization

Computational architecture and design course

Conventional construction methods all depart from the basic premises of mass production: standardization, modulation and a production line. What these systems developed during the last two centuries fail to take into account are the evolutionary leaps and bounds the manufacturing industry has taken over the last decades. With the introduction of CNC technologies and rapid prototyping machines have altered the paradigms of fabrication forever. It is due to these new tools that it is now possible to create (n) amount of completely unique and different pieces with the same amount of energy and material that is required to create (n) identical pieces. The possibilities for implementation of new forms, textures, materials and languages are infinite due to the versatility that these new tools offer a growing network of architects, designers, fabricators that are integrating them into their professional practices to generate unique and precise objects that respond to countless data and real-life conditions.

Instructors:

Monika Wittig [ LaN, IaaC ]

Shane Salisbury [ LaN, IaaC ]

Filippo Moroni [ SOLIDO, Politecnico di Milano ]

MS Josh Updyke [ Advanced Manufacturing Institute, KSU, Protei ]

Aaron Gutiérrez Cortes [ Amorphica ]