gebhart/patrepeval huggingface dataset:
Rapamycin has a biphasic effect on insulin sensitivity in C2C12 myotubes due to sequential disruption of mTORC1 and mTORC2 (2012)

Rapamycin, an inhibitor of mTOR complex 1 (mTORC1), improves insulin sensitivity in acute studies in vitro and in vivo by disrupting a negative feedback loop mediated by S6 kinase. We find that rapamycin has a clear biphasic effect on insulin sensitivity in C2C12 myotubes, with enhanced responsiveness during the first hour that declines to almost complete insulin resistance by 24-48 h. We and others have recently observed that chronic rapamycin treatment induces insulin resistance in rodents, at least in part due to disruption of mTORC2, an mTOR-containing complex that is not acutely sensitive to the drug. Chronic rapamycin treatment may also impair insulin action via the inhibition of mTORC1-dependent mitochondrial biogenesis and activity, which could result in a buildup of lipid intermediates that are known to trigger insulin resistance. We confirmed that rapamycin inhibits expression of PGC-1α, a key mitochondrial transcription factor, and acutely reduces respiration rate in myotubes. However, rapamycin did not stimulate phosphorylation of PKCΘ, a central mediator of lipid-induced insulin resistance. Instead, we found dramatic disruption of mTORC2, which coincided with the onset of insulin resistance. Selective inhibition of mTORC1 or mTORC2 by shRNA-mediated knockdown of specific components (Raptor and Rictor, respectively) confirmed that mitochondrial effects of rapamycin are mTORC1-dependent, whereas insulin resistance was recapitulated only by knockdown of mTORC2.Thus, mTORC2 disruption, rather than inhibition of mitochondria, causes insulin resistance in rapamycin-treated myotubes, and this system may serve as a useful model to understand the effects of rapamycin on mTOR signaling in vivo.
Multicenter trials using FDG PET to predict chemotherapy response: Effects of differential measurement error and bias on study power (2012)

1224 Objectives Quantitative measures of [18F]-FDG uptake from PET scans show promise as early response indicators and predictive biomarkers. However, in multicenter trials substantial measurement error and bias may arise from differences in scanner calibration, patient factors, scanning, and image analysis procedures. We simulated power calculations to inform study design, balancing faster accrual with increased measurement error. Methods Reference standardized uptake value (SUV) data were selected with replacement from a single-institution trial using FDG PET to measure breast cancer response to neoadjuvant chemotherapy; response data were simulated by logistic regression predicting response by mid-therapy percent change in SUV. The impact of increased error for multicenter trials was simulated using increased measurement error and bias. We examined different scenarios for bias and error added to SUVs: 20%-40% measurement error, 0%-40% bias, and fixed bias/error values. The proportion of patients recruited from sites with higher vs. lower additional bias/error varied from 25% to 75%. Results Reference power (from source data with no added error) was 0.92 for n=100 to detect an association between percentage change in SUV and response. With moderate (20%) additional measurement error for 3/4, 1/2, and 1/4 of measurements and 40% for the remainder, power was 0.70, 0.61, and 0.53 respectively. Reduction of study power was similar for other manifestations of measurement error (bias as a percentage of true value, absolute error, and absolute bias). Enrichment designs, which recruit additional patients by not conducting a second scan in patients with low baseline SUV, did not lead to greater power. Conclusions Rigorous characterization and quantification of bias and error, and harmonization of standards, are needed for accurate design of effective multicenter clinical trials incorporating PET. Research Support NIH grant U01CA148131, NCI Contract 24XS036-00
Delivery platforms for broadly neutralizing antibodies (2023)

The use of these different platforms for antibody delivery has been demonstrated across a wide range of animal models and disease indications, including HIV. Although each approach has unique strengths and weaknesses, additional advances in efficiency of gene delivery and reduced immunogenicity will be necessary to drive widespread implementation of these technologies. Considering the mounting clinical evidence of the potential of bNAbs for HIV treatment and prevention, overcoming the remaining technical challenges for gene-based bNAb delivery represents a relatively straightforward path towards practical interventions against HIV infection.
Fine Analysis of Immunoreactivity of V3 Peptides: Antibodies Specific for V3 Domain of Laboratory HIV Type 1 Strains Recognize Multiple V3 Sequences Synthesized from Field HIV Type 1 Isolates (1996)

Production of cross-reactive antibodies recognizing the V3 loop--that is, the principal neutralizing determinant (PND)--of various HIV-1 isolates is an important challenge in the development of passive immunotherapy or vaccinations against AIDS. We have produced two types of antibodies to the V3 domain of HIV-1: (1) antibodies against the HIV-1 MN laboratory strain generated in rabbits and (2) antibodies targeted to the HIV-1 LAI laboratory strain induced in chimpanzees. These antibodies were shown to be specific for HIV-1 subtype B. The cross-reactivity of these antibodies has been evaluated against a large panel of peptides representing different parts of the V3 loop. Seventy-five peptides, referred to as clinical peptides, were synthesized according to HIV-1 sequences recovered from PMBCs of 27 patients followed in three Parisian hospitals. Thirteen V3 peptides derived from 4 HIV-1 laboratory strains (MN, LAI, SF2, and RF) were also included in the study. The results show that both the amino-terminal and central parts of the V3 loop are immunogenic. The rabbit antibodies against the amino-terminal end of the PND proved to be highly cross-reactive against the clinical peptides. The anti-gp160 antibodies induced in one chimpanzee recognized a significant proportion of the panel of V3 clinical sequences. These antibodies cross-reacted mainly with the apex of the V3 loop. These data give some additional indications on the immunogenicity of the V3 loop and further demonstrate that extensive cross-reactivity of anti-V3 antibodies can be obtained on field HIV-1 isolates despite the high variability of the V3 loop amino acid sequence.
Computing the structure of language for neuropsychiatric evaluation (2017)

We describe recent preliminary studies demonstrating that computational analysis of spoken and written language can provide for highly accurate diagnostics over a wide variety of psychiatric and neurologic conditions, including psychosis, drug abuse, Parkinson's, and Alzheimer's. These results are based on the mathematical formalization of psychiatric qualitative knowledge related to the characterization of the conditions (e.g., “derailment” in psychosis) and drug effects (e.g., increased intimacy/affection with the use of the recreational drug ecstasy), as well as novel linguistic feature extraction approaches. Moreover, we show novel results using publicly available text sources suggesting that 1) it is possible to define an embedding space that allows modeling of the vast language dimension into a smaller space to map and compare different conditions, and 2) computational studies of a public personality (Ronald Reagan) can likely yield novel insights into normal aging and neurodegenerative disorders. Finally, we discuss the implications for mental health (and possibly, computer science) of a systematic application of this methodology, extended to include similar readily available behavioral data such as voice and video.
BEDLAM: A Synthetic Dataset of Bodies Exhibiting Detailed Lifelike Animated Motion (2023)

We show, for the first time, that neural networks trained only on synthetic data achieve state-of-the-art accuracy on the problem of 3D human pose and shape (HPS) estimation from real images. Previous synthetic datasets have been small, unrealistic, or lacked realistic clothing. Achieving sufficient realism is non-trivial and we show how to do this for full bodies in motion. Specifically, our BEDLAM dataset contains monocular RGB videos with ground-truth 3D bodies in SMPL-X format. It includes a diversity of body shapes, motions, skin tones, hair, and clothing. The clothing is realistically simulated on the moving bodies using commercial clothing physics simulation. We render varying numbers of people in realistic scenes with varied lighting and camera motions. We then train various HPS regressors using BEDLAM and achieve state-of-the-art accuracy on real-image benchmarks despite training with synthetic data. We use BEDLAM to gain insights into what model design choices are important for accuracy. With good synthetic training data, we find that a basic method like HMR approaches the accuracy of the current SOTA method (CLIFF). BEDLAM is useful for a variety of tasks and all images, ground truth bodies, 3D clothing, support code, and more are available for research purposes. Additionally, we provide detailed information about our synthetic data generation pipeline, enabling others to generate their own datasets. See the project page: https://bedlam.is.tue.mpg.de/.
Laser Desorption Fourier Transform Mass Spectrometry Exchange Studies of Air-Oxidized Alkanethiol Self-Assembled Monolayers on Gold (1997)

Exchange of self-assembled monolayers (SAMs) of dodecanethiol (C12H25SH) on gold with decanethiol (C10H21SH) was detected with laser-desorption Fourier transform mass spectrometry (LD-FTMS) in the negative ion mode. The amount of adsorption of C10H21SH is dependent on the extent of air oxidation of the C12H25SH SAM. In this study, a partially air oxidized C12H25SH SAM with a 2.2:1.5:1 ratio of dodecanethiolate (C12H25S-, m/z 201) to the presumed dodecanesulfinate (C12H25SO2-, m/z 233) to dodecanesulfonate (C12H25SO3-, m/z 249) on the surface is examined. After the sample is soaked in an ethanol solution of C10H21SH for 30 min, the LD-FTMS spectrum shows that both the C12H25SO2- and the C21H25SO3- are gone, but a decanethiolate peak appears (C10H21S-, m/z 173) in the same ratio to C12H25S- (1.19) as the ratio of the combined oxidation products (1.16) prior to soaking. Subsequent air exposure (9 h) of this SAM composed of mixed thiolates gives a similar ratio (1.06) of the fully oxidized sulfonates of both species, which can be completely removed upon subsequent soaking in a solution of C12H25SH, resulting in a SAM of pure dodecanethiolate by FTMS analysis. Negligible exchange occurs when nonoxidized C12H25SH SAMs are soaked in decanethiol solution for 30 min. From these observations, we draw several conclusions. First, the results refute suspicions that sulfonates form in a laser-induced reaction of thiolates with O2 absorbed in the SAM during air exposure. Second, ionization efficiency of thiolates and sulfonates during LD-FTMS analysis is approximately equal. Third, previous literature reports of exchange experiments should be carefully scrutinized for possible evidence of the effects of air oxidation.
Process Intensive Synthesis of Propofol Enabled by Continuous Flow Chemistry (2022)

A multi-step process using continuous flow chemistry to produce propofol is described. A scale-up of a 5-stage process (two continuous flow chemical steps, two extractions using a semi-batch approach, and one purification) provided propofol in high purity. This process minimizes the number of impurities formed during the double Friedel–Crafts reaction allowing to run two continuous flow chemical steps sequentially. The use of simple, inexpensive, and readily available reagents affords a viable process for this widely employed active pharmaceutical ingredient.
Body-Worn Distributed MIMO System (2008)

In this paper, we analyze the performance of novel wearable multiple-input-multiple-output (MIMO) systems, which consist of multiple electrotextile wearable antennas distributed at different locations on human clothing. For wearable applications, a semidirectional radiation pattern of the wearable patch antenna is preferred over an omnidirectional radiation of conventional dipole antennas to avoid unnecessary radiation exposure to the human body and radiation losses. Additionally, the spatial distribution of the antennas is not constrained as a typical handheld unit. Through theoretical modeling and simulation, the wearable MIMO system is shown to demonstrate a significantly higher channel capacity than a conventional system on a handheld platform (e.g., a compact dipole array or a single dipole), due to enhanced spatial diversity and antenna pattern diversity. The unique effects of antenna directivity and location on the MIMO system capacity are investigated in terms of antenna correlation and effective gain under different wireless channel models. The advantage of a wearable system over a conventional system was further confirmed by detailed physical modeling through the combination of full-wave electromagnetic and ray-tracing simulations. Finally, complex channel response matrices were measured to characterize the performance of a body-worn MIMO system in comparison with a reference full-size dipole antenna. The 319% improvement in 10% outage capacity for the body-worn system over the reference system made of a full-size dipole antenna is consistent with the 288% improvement projected by theoretical modeling and the average 300% improvement found in the physical simulation of two typical indoor scenarios.
Simulation of shear wave elasticity imaging including speckle and refraction effects (2015)

We present an overview of, and results from, a GPU-accelerated, 3D finite-difference time-domain acoustic radiation force impulse (ARFI) shear wave elasticity imaging (SWEI) simulator recently developed in our laboratory. The simulator allows modeling of the ultrasound “push” beam used to generate the shear wave, propagation of the shear wave in a viscoelastic, inhomogeneous medium, and simulation of ultrasound tracking of the shear wave. Spatial variations in both the ultrasound and shear wave speeds can be included to model ultrasound beam refraction errors and shear wave reflection and refraction by inclusions. Speckle has been shown experimentally to induce distortions in the apparent shape of a tracked shear wave, as well as biases in shear wave arrival time estimates used to generate shear wave speed images. A complete simulation of fully developed speckle captures this speckle bias effect but is time consuming. We present a dominant-speckle simulation approach that allows realistic modeling of the speckle-noise induced noise observed in videos of shear wave propagation in distributed speckle targets, and of artifacts in shear wave speed images. Matched simulation and phantom images of uniform and spherical inclusion targets are presented to demonstrate the ability of the simulation to capture key effects.
Packaging Issues and Solutions for Ultra-Low Power, High Efficiency GaN micro-LEDs for a Battery Free, Sub-mm2, Tetherless, Smart IoT System (2020)

Abstract This paper discusses some design and implementation issues related to GaN micro-LED (μLED) incorporated into the heterogeneous packaging of IBM’s smart and secure sensor platform. For cost effective μLEDs, the sapphire substrate needs to be singulated reliably and with minimum kerf perimeter, be ultra-clean and smooth to allow back side emission without scattering, and high yielding front side flip chip bonding with 20μm C4s on 40μm pitch. The GaN μLEDs are design for low voltage/low power operation with an emission area of 20μm × 20μm with critical current density of ~10nA/μm2. Power and downlink data is delivered to the system via optical energy harvesting by on-silicon carrier photovoltaics and communication photodiode, respectively. Optical amplitude modulated uplink communication by heterogeneous packaging of the GaN μLED with a 14nm CMOS smart chip will be detailed and demonstrated in presentation.
Graft Healing Is More Important Than Graft Technique: Superior Capsular Reconstruction Versus Bridging Grafts—A Prospective Randomized Controlled Trial (2022)

I, therapeutic.
Title: Using Alignment and 2D Network Simulations to Study Charge Transport Through Doped ZnO Nanowire Thin Film Electrodes (2011)

Abstract Factors affecting charge transport through ZnO nanowire mat films were studied by aligning ZnO nanowires on substrates and coupling experimental measurements with 2D nanowire network simulations. Gallium doped ZnO nanowires were aligned on thermally oxidized silicon wafer by shearing a nanowire dispersion in ethanol. Sheet resistances of nanowire thin films that had current flowing parallel to nanowire alignment direction were compared to thin films that had current flowing perpendicular to nanowire alignment direction. Perpendicular devices showed ∼5 fold greater sheet resistance than parallel devices supporting the hypothesis that aligning nanowires would increase conductivity of ZnO nanowire electrodes. 2‐D nanowire network simulations of thin films showed that the device sheet resistance was dominated by inter‐wire contact resistance. For a given resistivity of ZnO nanowires, the thin film electrodes would have the lowest possible sheet resistance if the inter‐wire contact resistance was one order of magnitude lower than the single nanowire resistance. Simulations suggest that the conductivity of such thin film devices could be further enhanced by using longer nanowires.
Serotonergic neuron regulation informed by in vivo single‐cell transcriptomics (2013)

Despite the recognized importance of the dorsal raphe (DR) serotonergic (5-HT) nuclei in the pathophysiology of depression and anxiety, the molecular components/putative drug targets expressed by these neurons are poorly characterized. Utilizing the promoter of an ETS domain transcription factor that is a stable marker of 5-HT neurons (Pet-1) to drive 5-HT neuronal expression of YFP, we identified 5-HT neurons in live acute slices. We isolated RNA from single 5-HT neurons in the ventromedial and lateral wings of the DR and performed single-cell RNA-Seq analysis identifying >500 G-protein coupled receptors (GPCRs) including receptors for classical transmitters, lipid signals, and peptides as well as dozens of orphan-GPCRs. Using these data to inform our selection of receptors to assess, we found that oxytocin and lysophosphatidic acid 1 receptors are translated and active in costimulating, with the α1-adrenergic receptor, the firing of DR 5-HT neurons, while the effects of histamine are inhibitory and exerted at H3 histamine receptors. The inhibitory histamine response provides evidence for tonic in vivo histamine inhibition of 5-HT neurons. This study illustrates that unbiased single-cell transcriptomics coupled with functional analyses provides novel insights into how neurons and neuronal systems are regulated.
Both Disease Activity and HLA–B27 Status Are Associated With Gut Microbiome Dysbiosis in Spondyloarthritis Patients (2022)

Objective Gut microbiome dysbiosis has previously been reported in spondyloarthritis (SpA) patients and could be critically involved in the pathogenesis of this disorder. The objectives of this study were to further characterize the microbiota structure in SpA patients and to investigate the relationship between dysbiosis and disease activity in light of the putative influence of the genetic background. Methods Shotgun sequencing was performed on fecal DNA isolated from stool samples from 2 groups of adult volunteers: SpA patients (n = 102) and healthy controls (n = 63). A subset of the healthy controls comprised the age‐matched siblings of patients whose HLA–B27 status was known. Changes in gut microbiota composition were assessed based on species diversity, enterotypes, and taxonomic and functional differences. Results Dysbiosis was confirmed in SpA patients as compared to healthy controls. The restriction of microbiota diversity was detected in patients with the most active disease, and the abundance of several bacterial species was correlated with Bath Ankylosing Spondylitis Disease Activity Index score. Among healthy controls, significant differences in microbiota composition were also detected between the HLA–B27–positive and the HLA–B27–negative siblings of SpA patients. We highlighted a decreased abundance of several species of bacteria in SpA patients, especially those bacteria belonging to the Clostridiales order. Among the few species of bacteria showing increased abundance, Ruminococcus gnavus was one of the top differentiating species. Conclusion These findings reveal that genetic background and level of disease activity are likely to influence the composition of the gut microbiota of patients with SpA. It may be appropriate for further research on chronic arthritis to focus on these key parameters.
A chemoenzymatic strategy for site-selective functionalization of native peptides and proteins (2022)

The emergence of new therapeutic modalities requires complementary tools for their efficient syntheses. Availability of methodologies for site-selective modification of biomolecules remains a long-standing challenge, given the inherent complexity and the presence of repeating residues that bear functional groups with similar reactivity profiles. We describe a bioconjugation strategy for modification of native peptides relying on high site selectivity conveyed by enzymes. We engineered penicillin G acylases to distinguish among free amino moieties of insulin (two at amino termini and an internal lysine) and manipulate cleavable phenylacetamide groups in a programmable manner to form protected insulin derivatives. This enables selective and specific chemical ligation to synthesize homogeneous bioconjugates, improving yield and purity compared to the existing methods, and generally opens avenues in the functionalization of native proteins to access biological probes or drugs.
Use of PML boundary conditions for wireless telephone simulations (1997)

Previous articles on the perfectly matched layer (PML) boundary condition have focused on the reflections from the boundary itself. This article examines an application of the PML boundary condition to determine if it is preferable to use the PML or the more traditional boundary conditions for finite-difference-time-domain (FDTD) simulations of personal wireless telephones. Retarded time and PML boundary conditions are compared in realistic simulations of cellular telephones operating at 835 and 1900 MHz held against the human head. The peak 1-specific absorption rate (SAR) values, total percent power absorbed, impedance, and radiation patterns are compared, and it is shown that the two boundary conditions provide virtually identical results to within 3% for impedance and 1% for other values, and require similar computer resources. This demonstrates that the PML and retarded time boundary conditions are equally accurate for FDTD cellular telephone simulations and can be used with approximately equal efficiency. © 1997 John Wiley & Sons, Inc. Microwave Opt Technol Lett 15: 95–98, 1997.