gebhart/patrepeval huggingface dataset:
Mass Spectrometry–Based Protein Biomarker Discovery: Solving the Remaining Challenges to Reach the Promise of Clinical Benefit (2010)

This report in The Lancet generated a great deal of excitement about the application of mass spectrometry (MS) to discover candidate protein biomarkers for early-stage ovarian cancer. MS-based serum/plasma biomarker profiling was launched in a flourish of optimism to meet the urgent need for biomarkers of earlystage cancer, a need that still exists today. Before 1998, very few investigators used MS (MALDI-TOF or electrospray ionization) to directly analyze blood, because serum was considered too complex and "dirty" for direct introduction into expensive and sophisticated MS research instruments. The door was opened to the use of MS for biomarker research in 1998 with SELDI, a new modification of MALDI-TOF technology. Researchers were immediately intrigued by the SELDI-TOF approach because body fluids could be applied directly to the chip surface and then analyzed to generate an ion fingerprint (1, 2 ). SELDI had relatively low resolution and could not identify the ions directly. Nevertheless, it provided a fresh approach in the search for the ion signatures of hundreds of candidate biomarkers. We saw SELDI-TOF as a means to test a new hypothesis that was emerging in the protein biomarker field. Investigators had proposed that tumor-host interactions in the tissue microenvironment were generating cascades of biomarkers. A corollary of the hypothesis was that a panel of biomarkers could achieve diagnostic sensitivity and specificity superior to those of previously failed one-at-a-time searches for cancer biomarkers.
Desmoglein 3–specific CD4+ T cells induce pemphigus vulgaris and interface dermatitis in mice (2011)

Pemphigus vulgaris (PV) is a severe autoimmune disease involving blistering of the skin and mucous membranes. It is caused by autoantibodies against desmoglein 3 (Dsg3), an adhesion molecule critical for maintaining epithelial integrity in the skin, oral mucosa, and esophagus. Knowing the antigen targeted by the autoantibodies renders PV a valuable model of autoimmunity. Recently, a role for Dsg3-specific CD4+ T helper cells in autoantibody production was demonstrated in a mouse model of PV, but whether these cells exert cytotoxicity in the tissues is unclear. Here, we analyzed 3 Dsg3-specific TCRs using transgenic mice and retrovirus induction. Dsg3-specific transgenic (Dsg3H1) T cells underwent deletion in the presence of Dsg3 in vivo. Dsg3H1 T cells that developed in the absence of Dsg3 elicited a severe pemphigus-like phenotype when cotransferred into immunodeficient mice with B cells from Dsg3-/- mice. Strikingly, in addition to humoral responses, T cell infiltration of Dsg3-expressing tissues led to interface dermatitis, a distinct form of T cell-mediated autoimmunity that causes keratinocyte apoptosis and is seen in various inflammatory/autoimmune skin diseases, including paraneoplastic pemphigus. The use of retrovirally generated Dsg3-specific T cells revealed that interface dermatitis occurred in an IFN-γ- and TCR avidity-dependent manner. This model of autoimmunity demonstrates that T cells specific for a physiological skin-associated autoantigen are capable of inducing interface dermatitis and should provide a valuable tool for further exploring the immunopathophysiology of T cell-mediated skin diseases.
Nanoscale Polymer Processing (2008)

Nanometer-scale capillary-driven flow and molecular weight govern polymer nanostructure deposition from a heated tip,
Scheduling and Codeword Length Optimization in Time Varying Wireless Networks (2006)

In this paper, a downlink scenario in which a single-antenna base station communicates with K single antenna users, over a time-correlated fading channel, is considered. It is assumed that channel state information is perfectly known at each receiver, while the statistical characteristics of the fading process and the fading gain at the beginning of each frame are known to the transmitter. By evaluating the random coding error exponent of the time-correlated fading channel, we show that there is an optimal codeword length which maximizes the throughput. We examine the throughput of the conventional scheduling that transmits to the user with the maximum signal to noise ratio using both fixed length codewords and variable length codewords. Although optimizing the codeword length improves the performance, it is shown that using the conventional scheduling, a gap of Omega(radiclog log log K) exists between the achievable throughput and the maximum possible throughput of the system. We propose a simple scheduling that considers both the signal to noise ratio and the channel time variation. We show that by using this scheduling, the gap between the achievable throughput and the maximum throughput of the system approaches zero
Context menus for the real world (2009)

In this video, we present a context-aware menu system made out of simulated digital paper. Built on the ubiquitous yellow sticky notes found in offices everywhere, our computer provides a contextual interactive paper menu that can be used to operate numerous everyday electric and electronic devices, such as lamps, speakers and computers. Stuck on a device, the sticky screen displays contextual information and control options which may be selected with a single touch of the finger. The stick-anywhere computer is an example of a context-aware organic user interface that, through a flexible paper-like display, allows software to reside directly on the product or task. The Stick-Anywhere Computer was implemented using a Xuuk Eyebox2 IR camera that tracks nearly invisible IR markers on post-it notes as well as fingers, and uses a projector to render interactive content directly onto the paper note.
Disruption of Neutrophil Migration in a Conditional Transgenic Model: Evidence for CXCR2 Desensitization In Vivo (2001)

We developed transgenic mice conditionally expressing the neutrophil chemoattracting chemokine KC and the beta-galactosidase gene in multiple tissues. In these transgenic mice, doxycycline treatment induced a strong up-regulation in the expression of KC in several tissues, including heart, liver, kidney, skin, and skeletal muscle. Expression of KC within these tissues led to a rapid and substantial increase in the serum levels of KC (serum KC levels were higher than 200 ng/ml 24 h after treatment). Accordingly, beta-galactosidase expression was also detected after injection of doxycycline and was highest in skeletal muscle, pancreas, and liver. Surprisingly, despite expression of KC in multiple tissues, no neutrophil infiltration was observed in any of the tissues examined, including skin. Doxycycline treatment of nontransgenic mice grafted with transgenic skin caused dense neutrophilic infiltration of the grafts, but not the surrounding host skin, indicating that the KC produced in transgenic tissues was biologically active. In separate experiments, neutrophil migration toward a localized source of recombinant KC was impaired in animals overexpressing KC but was normal in response to other neutrophil chemoattractants. Analysis of transgenic neutrophils revealed that high concentrations of KC in transgenic blood had no influence on L-selectin cell surface expression but caused desensitization of the receptor for KC, CXCR2. These results confirm the neutrophil chemoattractant properties of KC and provide a mechanistic explanation for the paradoxical lack of leukocyte infiltration observed in the presence of elevated concentrations of this chemokine.
Population dynamics of choice representation in dorsal premotor and primary motor cortex (2018)

Summary Studies in multiple species have revealed the existence of neural signals that lawfully co-vary with different aspects of the decision-making process, including choice, sensory evidence that supports the choice, and reaction time. These signals, often interpreted as the representation of a decision variable (DV), have been identified in several motor preparation circuits and provide insight about mechanisms underlying the decision-making process. However, single-trial dynamics of this process or its representation at the neural population level remain poorly understood. Here, we examine the representation of the DV in simultaneously recorded neural populations of dorsal premotor (PMd) and primary motor (M1) cortices of monkeys performing a random dots direction discrimination task with arm movements as the behavioral report. We show that single-trial DVs covary with stimulus difficulty in both areas but are stronger and appear earlier in PMd compared to M1 when the stimulus duration is fixed and predictable. When temporal uncertainty is introduced by making the stimulus duration variable, single-trial DV dynamics are accelerated across the board and the two areas become largely indistinguishable throughout the entire trial. These effects are not trivially explained by the faster emergence of motor kinematic signals in PMd and M1. All key aspects of the data were replicated by a computational model that relies on progressive recruitment of units with stable choice-related modulation of neural population activity. In contrast with several recent results in rodents, decision signals in PMd and M1 are not carried by short sequences of activity in non-overlapping groups of neurons but are instead distributed across many neurons, which once recruited, represent the decision stably during individual behavioral epochs of the trial.
On the Accuracy of Deterministic Models for Viral Spread on Networks (2021)

We consider the emergent behavior of viral spread when agents in a large population interact with each other over a contact network. When the number of agents is large and the contact network is a complete graph, it is well known that the population behavior -- that is, the fraction of susceptible, infected and recovered agents -- converges to the solution of an ordinary differential equation (ODE) known as the classical SIR model as the population size approaches infinity. In contrast, we study interactions over contact networks with generic topologies and derive conditions under which the population behavior concentrates around either the classic SIR model or other deterministic models. Specifically, we show that when most vertex degrees in the contact network are sufficiently large, the population behavior concentrates around an ODE known as the network SIR model. We then study the short and intermediate-term evolution of the network SIR model and show that if the contact network has an expander-type property or the initial set of infections is well-mixed in the population, the network SIR model reduces to the classical SIR model. To complement these results, we illustrate through simulations that the two models can yield drastically different predictions, hence use of the classical SIR model can be misleading in certain cases.
P‐74: Development of Reflective Color STN‐LCD Using a New Optimizing Method of Retarders and a Polarizer (1998)

Abstract Reflective color SIN ‐ LCDs are one of the most suitable displays for personal digital assistant applications, but their image quality has not yet reached the level to satisfy users' needs. Their image quality depends on many parameters such as absorption axis of the polarizer, optical axes and retardation of two retarders. A new optimization method is developed to improve image quality taking account of the polarization states of the light after reflection at the reflector.
Adapting Low-Bitrate Skip Mode in a Mobile Environment (2014)

A method is introduced to enhance the High Efficiency Video Coding early skip decision process. The proposed method exploits visual acuity and high-velocity motion perception of the human visual system (HVS). The method determines coding units where the HVS is unlikely to notice the changes and hence can be skipped. In this paper, the focus is mobile devices, such as smart phones, where displays are less than 5 in diagonal length and bandwidth availability is low. The proposed method exploits the mismatch between the video resolution, display resolution, and visual acuity of users. This method has very low impact on subjective quality while reducing encoding time for low bitrate environments. The proposed method reduces both encoding time and bitrate; the results show an average of 21.7% decrease in encoding time, 13.4% decrease in average bitrate, and very low impact on subjective quality ratings. The proposed methods can be adapted to decrease encoding time and bitrate in devices with lower resolution displays.
Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE) Based Diagnosis and Therapy (2013)

Claudins are a family of tight junction proteins regulating paracellular permeability and cell polarity with different patterns of expression in benign and malignant human tissues. There are approximately 27 members of the claudin family identified to date with varying cell and tissue-specific expression. Claudins-3, -4 and -7 represent the most highly differentially expressed claudins in ovarian cancer. While their exact role in ovarian tumors is still being elucidated, these proteins are thought to be critical for ovarian cancer cell invasion/dissemination and resistance to chemotherapy. Claudin-3 and claudin-4 are the natural receptors for the Clostridium perfringens enterotoxin (CPE), a potent cytolytic toxin. These surface proteins may therefore represent attractive targets for the detection and treatment of chemotherapy-resistant ovarian cancer and other aggressive solid tumors overexpressing claudin-3 and -4 using CPE-based theranostic agents.
Quantitative photoacoustic image reconstruction improves accuracy in deep tissue structures (2016)

Photoacoustic imaging (PAI) is emerging as a potentially powerful imaging tool with multiple applications. Image reconstruction for PAI has been relatively limited because of limited or no modeling of light delivery to deep tissues. This work demonstrates a numerical approach to quantitative photoacoustic image reconstruction that minimizes depth and spectrally derived artifacts. We present the first time-domain quantitative photoacoustic image reconstruction algorithm that models optical sources through acoustic data to create quantitative images of absorption coefficients. We demonstrate quantitative accuracy of less than 5% error in large 3 cm diameter 2D geometries with multiple targets and within 22% error in the largest size quantitative photoacoustic studies to date (6cm diameter). We extend the algorithm to spectral data, reconstructing 6 varying chromophores to within 17% of the true values. This quantitiative PA tomography method was able to improve considerably on filtered-back projection from the standpoint of image quality, absolute, and relative quantification in all our simulation geometries. We characterize the effects of time step size, initial guess, and source configuration on final accuracy. This work could help to generate accurate quantitative images from both endogenous absorbers and exogenous photoacoustic dyes in both preclinical and clinical work, thereby increasing the information content obtained especially from deep-tissue photoacoustic imaging studies.
Electro-optically-Q-switched Nd:YVO4 microchip lasers (1995)

Coupled-cavity electro-optically-Q-switched microchip lasers1 were constructed from 440-μm-long pieces of 1.1-wt.% Nd:YVO4 bonded to 900-μm-long pieces of LiTaO3, as illustrated in Fig. 1. Both materials were polished flat and parallel on the two faces normal to the cavity axis and were oriented with their c axes parallel to each other, orthogonal to the cavity axis. Electrodes were deposited on the faces of the LiTaO3 normal to the c axis, with an electrode spacing of ~1 mm. The pump-side faces of the Nd:YVO4 were coated dielectrically to transmit the pump light and to be highly reflective at the oscillating wavelength (1.064 μm). Greater than 90% of the incident 808-nm pump light from a butt-coupled fiber was absorbed by the gain medium.
HAWKEYE (2011)

Parallelization transformations are an important vehicle for improving the performance and scalability of a software system. Utilizing concurrency requires that the developer first identify a suitable parallelization scope: one that poses as a performance bottleneck, and at the same time, exhibits considerable available parallelism. However, having identified a candidate scope, the developer still needs to ensure the correctness of the transformation. This is a difficult undertaking, where a major source of complication lies in tracking down sequential dependencies that inhibit parallelization and addressing them. We report on Hawkeye, a dynamic dependence-analysis tool that is designed to assist programmers in pinpointing such impediments to parallelization. In contrast with field-based dependence analyses, which track concrete memory conflicts and thus suffer from a high rate of false reports, Hawkeye tracks dependencies induced by the abstract semantics of the data type while ignoring dependencing arising solely from implementation artifacts. This enables a more concise report, where the reported dependencies are more likely to be real as well as intelligible to the programmer.
Enhanced Light Utilization in Semitransparent Organic Photovoltaics Using an Optical Outcoupling Architecture (2019)

Building-integrated photovoltaics employing transparent photovoltaic cells on window panes provide an opportunity to convert solar energy to electricity rather than generating waste heat. Semitransparent organic photovoltaic cells (ST-OPVs) that utilize a nonfullerene acceptor-based near-infrared (NIR) absorbing ternary cell combined with a thin, semitransparent, high conductivity Cu-Ag alloy electrode are demonstrated. A combination of optical outcoupling and antireflection coatings leads to enhanced visible transmission, while reflecting the NIR back into the cell where it is absorbed. This combination of coatings results in doubling of the light utilization efficiency (LUE), which is equal to the product of the power conversion efficiency (PCE) and the average photopic transparency, compared with a conventional semitransparent cell lacking these coatings. A maximum LUE = 3.56 ± 0.11% is achieved for an ST-OPV with a PCE = 8.0 ± 0.2% at 1 sun, reference AM1.5G spectrum. Moreover, neutral colored ST-OPVs are also demonstrated, with LUE = 2.56 ± 0.2%, along with Commission Internationale d'Eclairage chromaticity coordinates of CIE = (0.337, 0.349) and a color rendering index of CRI = 87.
Combination of CDNF and Deep Brain Stimulation Decreases Neurological Deficits in Late-stage Model Parkinson’s Disease (2018)

Several neurotrophic factors (NTF) are shown to be neuroprotective and neurorestorative in pre-clinical animal models for Parkinson's disease (PD), particularly in models where striatal dopamine neuron innervation partially exists. The results of clinical trials on late-stage patients have been modest. Subthalamic deep brain stimulation (STN DBS) is a proven treatment for a selected group of advanced PD patients. The cerebral dopamine neurotrophic factor (CDNF) is a promising therapeutic protein, but its effects in animal models of late-stage PD have remained under-researched. The interactions of NTF and STN DBS treatments have not been studied before. We found that a nigral CDNF protein alone had only a marginal effect on the behavioral deficits in a late-stage hemiparkinsonian rat model (6-OHDA MFB). However, CDNF improved the effect of acute STN DBS on front limb use asymmetry at 2 and 3 weeks after CDNF injection. STN lesion-modeling chronic stimulation-had an additive effect in reducing front limb use in the cylinder test and apomorphine-induced rotation. The combination of CDNF and acute STN DBS had a favorable effect on striatal tyrosine hydroxylase. This study presents a novel additive beneficial effect of NTF and STN DBS, which might be explained by the interaction of DBS-induced endogenous NTFs and exogenously injected CDNF. SNpc can be reached via similar trajectories used in clinical STN DBS, and this interaction is an important area for future studies.
Regulatory T cell differentiation is controlled by αKG-induced alterations in mitochondrial metabolism and lipid homeostasis (2021)

Suppressive regulatory T cell (Treg) differentiation is controlled by diverse immunometabolic signaling pathways and intracellular metabolites. Here we show that cell-permeable α-ketoglutarate (αKG) alters the DNA methylation profile of naive CD4 T cells activated under Treg polarizing conditions, markedly attenuating FoxP3+ Treg differentiation and increasing inflammatory cytokines. Adoptive transfer of these T cells into tumor-bearing mice results in enhanced tumor infiltration, decreased FoxP3 expression, and delayed tumor growth. Mechanistically, αKG leads to an energetic state that is reprogrammed toward a mitochondrial metabolism, with increased oxidative phosphorylation and expression of mitochondrial complex enzymes. Furthermore, carbons from ectopic αKG are directly utilized in the generation of fatty acids, associated with lipidome remodeling and increased triacylglyceride stores. Notably, inhibition of either mitochondrial complex II or DGAT2-mediated triacylglyceride synthesis restores Treg differentiation and decreases the αKG-induced inflammatory phenotype. Thus, we identify a crosstalk between αKG, mitochondrial metabolism and triacylglyceride synthesis that controls Treg fate.
Functional transcriptomics of a migrating cell in Caenorhabditis elegans (2012)

In both metazoan development and metastatic cancer, migrating cells must carry out a detailed, complex program of sensing cues, binding substrates, and moving their cytoskeletons. The linker cell in Caenorhabditis elegans males undergoes a stereotyped migration that guides gonad organogenesis, occurs with precise timing, and requires the nuclear hormone receptor NHR-67. To better understand how this occurs, we performed RNA-seq of individually staged and dissected linker cells, comparing transcriptomes from linker cells of third-stage (L3) larvae, fourth-stage (L4) larvae, and nhr-67-RNAi-treated L4 larvae. We observed expression of 8,000-10,000 genes in the linker cell, 22-25% of which were up- or down-regulated 20-fold during development by NHR-67. Of genes that we tested by RNAi, 22% (45 of 204) were required for normal shape and migration, suggesting that many NHR-67-dependent, linker cell-enriched genes play roles in this migration. One unexpected class of genes up-regulated by NHR-67 was tandem pore potassium channels, which are required for normal linker-cell migration. We also found phenotypes for genes with human orthologs but no previously described migratory function. Our results provide an extensive catalog of genes that act in a migrating cell, identify unique molecular functions involved in nematode cell migration, and suggest similar functions in humans.