gebhart/patrepeval huggingface dataset:
Role of Essential Amino Acids in the Early Formation of Avian Liver Xanthine Dehydrogenase Activity (1957)

Avian liver xanthine dehydrogenase (LXD) has been shown to be sensitive to dietary proteins and amino acids particularly when measured during the first 3 weeks of life. Feeding an adequate diet for the first 7 days of life produces a condition wherein LXD is very resistant to single essential amino acid deficiencies. When an amino acid-deficient regimen is fed directly, without prefeeding an adequate diet, a rapid and marked decrease is seen which is inversely proportional to the amount of available limiting amino acid. This mechanism has also been demonstrated by LXD depletion with low dietary protein and repletion with diets high in protein but limiting in a specific amino acid. In the case of l-threonine deficiency, a dietary level of threonine above that required to saturate a growth response produced a continuous rise in LXD specific activity similar to induction.
Defining the Genes Required for Survival of Mycobacterium bovis in the Bovine Host Offers Novel Insights into the Genetic Basis of Survival of Pathogenic Mycobacteria (2022)

Tuberculosis has severe impacts on both humans and animals. Understanding the genetic basis of survival of both Mycobacterium tuberculosis, the human-adapted species, and Mycobacterium bovis, the animal-adapted species, is crucial to deciphering the biology of both pathogens. There are several studies that identify the genes required for survival of M. tuberculosis <i>in vivo</i> using mouse models; however, there are currently no studies probing the genetic basis of survival of M. bovis <i>in vivo.</i> In this study, we utilize transposon insertion sequencing in M. bovis AF2122/97 to determine the genes required for survival in cattle. We identify genes encoding established mycobacterial virulence functions such as the ESX-1 secretion system, phthiocerol dimycocerosate (PDIM) synthesis, mycobactin synthesis, and cholesterol catabolism that are required <i>in vivo</i>. We show that, as in M. tuberculosis H37Rv, <i>phoPR</i> is required by M. bovis AF2122/97 <i>in vivo</i> despite the known defect in signaling through this system. Comparison to studies performed in species that are able to use carbohydrates as an energy source, such as M. bovis BCG and M. tuberculosis, suggests that there are differences in the requirement for genes involved in cholesterol import (<i>mce4</i> operon) and oxidation (<i>hsd</i>). We report a good correlation with existing mycobacterial virulence functions but also find several novel virulence factors, including genes involved in protein mannosylation, aspartate metabolism, and glycerol-phosphate metabolism. These findings further extend our knowledge of the genetic basis of survival <i>in vivo</i> in bacteria that cause tuberculosis and provide insight for the development of novel diagnostics and therapeutics. <b>IMPORTANCE</b> This is the first report of the genetic requirements of an animal-adapted member of the Mycobacterium tuberculosis complex (MTBC) in a natural host. M. bovis has devastating impacts on cattle, and bovine tuberculosis is a considerable economic, animal welfare, and public health concern. The data highlight the importance of mycobacterial cholesterol catabolism and identify several new virulence factors. Additionally, the work informs the development of novel differential diagnostics and therapeutics for TB in both human and animal populations.
Signatures of selection in the human antibody repertoire: Selective sweeps, competing subclones, and neutral drift (2019)

Antibodies are created and refined by somatic evolution in B cell populations, which endows the human immune system with the ability to recognize and eliminate diverse pathogens. However, the evolutionary processes that sculpt antibody repertoires remain poorly understood. Here, using an unbiased repertoire-scale approach, we show that the population genetic signatures of evolution are evident in human B cell lineages and reveal how antibodies evolve somatically. We measured the dynamics and genetic diversity of B cell responses in five adults longitudinally before and after influenza vaccination using high-throughput antibody repertoire sequencing. We identified vaccine-responsive B cell lineages that carry signatures of selective sweeps driven by positive selection, and discovered that they often display evidence for selective sweeps favoring multiple subclones. We also found persistent B cell lineages that exhibit stable population dynamics and carry signatures of neutral drift. By exploiting the relationship between B cell fitness and antibody binding affinity, we demonstrate the potential for using phylogenetic approaches to identify antibodies with high binding affinity. This quantitative characterization reveals that antibody repertoires are shaped by an unexpectedly broad spectrum of evolutionary processes and shows how signatures of evolutionary history can be harnessed for antibody discovery and engineering.
Mechatronic design of an actuated biomimetic length and velocity sensor. (2004)

Biological designs offer roboticists a rich source of mechanisms for the challenge of controlling movement. Our device draws upon this resource, modeling the muscle spindle, a biological sensor which transduces muscle length and velocity for kinesthetic awareness and movement control. The three core neural and mechanical elements of the muscle spindle are identified and implemented in precision engineering hardware using performance specifications derived from biological literature. Intrafusal muscle is modeled by a linear actuator fast enough to replicate muscle dynamics. Its step response exhibits 27 ms rise time and 9.2% overshoot. Sensory region transduction of strain into voltage is modeled by a strain-gauged cantilever 51 /spl mu/m thick. A voltage-controlled oscillator, encoding voltage as a frequency-modulated square wave, models action potential frequency encoding. The transducer exhibits the desired linear response with a 34-nm/Hz sensitivity. The three subsystems were combined to perform integrated systems testing. Driving the actuator with simple position control, the device detects trajectory-tracking errors introduced by phase lag and perturbation. Driving the actuator with physiologically based force control, the device successfully replicates the major features of muscle spindle response under ramp and sinusoidal position inputs. Applications include motor control research and novel sensor design for prosthetics and engineering.
Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection (2020)

Effective therapies are urgently needed for the SARS-CoV-2/COVID-19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from large phage-displayed Fab, scFv, and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. A high-affinity Fab was selected from one of the libraries and converted to a full-size antibody, IgG1 ab1, which competed with human ACE2 for binding to RBD. It potently neutralized replication-competent SARS-CoV-2 but not SARS-CoV, as measured by two different tissue culture assays, as well as a replication-competent mouse ACE2-adapted SARS-CoV-2 in BALB/c mice and native virus in hACE2-expressing transgenic mice showing activity at the lowest tested dose of 2 mg/kg. IgG1 ab1 also exhibited high prophylactic and therapeutic efficacy in a hamster model of SARS-CoV-2 infection. The mechanism of neutralization is by competition with ACE2 but could involve antibody-dependent cellular cytotoxicity (ADCC) as IgG1 ab1 had ADCC activity in vitro. The ab1 sequence has a relatively low number of somatic mutations, indicating that ab1-like antibodies could be quickly elicited during natural SARS-CoV-2 infection or by RBD-based vaccines. IgG1 ab1 did not aggregate, did not exhibit other developability liabilities, and did not bind to any of the 5,300 human membrane-associated proteins tested. These results suggest that IgG1 ab1 has potential for therapy and prophylaxis of SARS-CoV-2 infections. The rapid identification (within 6 d of availability of antigen for panning) of potent mAbs shows the value of large antibody libraries for response to public health threats from emerging microbes.
Ultrahard diamond indenter prepared from nanopolycrystalline diamond (2008)

Knoop indenters were prepared from nanopolycrystalline diamonds (NPDs) synthesized by direct conversion sintering from graphite under high pressure and high temperature. Owing to the fine structure (grain size: 10-100 nm) of NPD, high-accuracy sharp edges could be formed at the indenter tips. The indentation tests demonstrated that the NPD indenter can form normal (measurable) indentations on NPD samples without fracture or chipping even at high temperatures of up to 1000 degrees C, while conventional indenters made of single-crystal diamonds break easily above 600 degrees C. This suggests that the NPD indenter has greater potential in high-temperature hardness tests than the conventional single-crystal diamond indenters.
Polymerization Kinetics and Monomer Functionality Effects in Thiol−Ene Polymer Dispersed Liquid Crystals (2007)

Polymer dispersed liquid crystals (PDLCs) are a class of electrooptic materials most often formed by polymer-induced phase separation, a one-step fabrication technique often based on photopolymerization of the commercial thiol−ene mixture NOA65. To allow further understanding regarding PDLC formation, this work systematically examines processing variables that influence thiol−ene-based PDLC morphology and subsequent performance, namely polymerization kinetics, polymer gel point, and liquid crystal (LC) phase separation. PDLC formulations containing a wide range of thiol and ene monomers were examined as a function of monomer (thiol and ene) functionality, thiol−ene stoichiometry, and ene monomer composition. Simultaneous examination of polymer evolution and LC phase separation by real-time infrared (RTIR) spectroscopy shows that both polymerization kinetics and the gel point of thiol−ene PDLC formulations are influential on the extent of LC phase separation. Increasing monomer functionality (both thiol and ene) reduces LC droplet size in PDLC morphology by reducing the gel point conversion of thiol−ene polymer. In addition to influencing gelation, increasing the functionality or the electron density of ene monomer increases the rate of polymerization which further reduces LC droplet size. The thiol−ene PDLC formulations studied exhibit decreased LC droplet size (from 1 μm to 300 nm) that correlates directly to polymerization rate and gel point. Electrooptic switching behavior is also dependent on LC droplet size.
ORCAS: 18 Million Clicked Query-Document Pairs for Analyzing Search (2020)

Users of Web search engines reveal their information needs through queries and clicks, making click logs a useful asset for information retrieval. However, click logs have not been publicly released for academic use, because they can be too revealing of personally or commercially sensitive information. This paper describes a click data release related to the TREC Deep Learning Track document corpus. After aggregation and filtering, including a k -anonymity requirement, we find 1.4 million of the TREC DL URLs have 18 million connections to 10 million distinct queries. Our dataset of these queries and connections to TREC documents is of similar size to proprietary datasets used in previous papers on query mining and ranking. We perform some preliminary experiments using the click data to augment the TREC DL training data, offering by comparison: 28x more queries, with 49x more connections to 4.4x more URLs in the corpus. We present a description of the dataset's generation process, characteristics, use in ranking and other potential uses.
Electrode Corrosion in a Compartmented Flow Cell by Diffusion from the Counterelectrode (1983)

Electrode corrosion by a soluble species diffusing from the counterelectrode in a circulating flow cell has been analyzed. The net rate of corrosion and its distribution along the electrode are found to be governed by two dimensionless parameters, representing ratios of mass transfer and kinetic resistances. Application of this analysis to a zinc‐bromine flow cell indicates that corrosion of the zinc electrode by dissolved bromine is mass‐transfer controlled. Using the experimentally measured bromine diffusion coefficient and an estimated kinetic rate constant, the average zinc corrosion rate in a typical zinc‐bromine cell is calculated to be in the range of 1 mA/cm2, if a typical bromine concentration in the positive channel (10 g/liter) is assumed.
<em>Age- and Genotype-Specific Effects of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Mitochondrial and Metabolic Parameters in Drosophila melanogaster</em> (2018)

The angiotensin-converting enzyme (ACE) is a peptidase that is involved in the synthesis of Angiotensin II, the bioactive component of the renin-angiotensin system. A growing body of literature argues for a beneficial impact of ACE inhibitors (ACEi) on age-associated metabolic disorders, mediated by cellular changes in reactive oxygen species (ROS) that improve mitochondrial function. Yet, our understanding of the relationship between ACEi therapy and metabolic parameters is limited. Here, we used three genetically diverse strains of Drosophila melanogaster to show that Lisinopril treatment reduces thoracic ROS levels and mitochondrial respiration in young flies, and increases mitochondrial content in middle-aged flies. Using untargeted metabolomics analysis, we also showed that Lisinopril perturbs the thoracic metabolic network structure by affecting metabolic pathways involved in glycogen degradation, glycolysis, and mevalonate metabolism. The Lisinopril-induced effects on mitochondrial and metabolic parameters, however, are genotype-specific and likely reflect the drug&amp;rsquo;s impact on nutrient-dependent fitness traits. Accordingly, we found that Lisinopril negatively affects survival under nutrient starvation, an effect that can be blunted by genotype and age in a manner that partially mirrors the drug-induced changes in mitochondrial respiration. In conclusion, our results provide novel and important insights into the role of ACEi in cellular metabolism.
DNA Array Analysis of Changes in Preovulatory Gene Expression in the Rat Ovary1 (2001)

During the periovulatory period, the mammalian ovary is the site of dramatic functional and structural changes, leading to oocyte maturation, follicle rupture, and corpus luteum formation. To a large extent, these processes result from changes in the transcriptome of various ovarian cell types. To develop a broader view of periovulatory changes in gene expression in the ovary and to identify further genes involved in periovulatory events, we used the recently developed DNA array technology. Immature female eCG-primed rats were killed either immediately before or 6 h after ovulation induction with hCG. Total ovarian RNA was isolated and used to prepare radiolabeled cDNA probes, which were hybridized to DNA arrays representing approximately 600 rat genes. Quantitative analysis identified a multitude of regulated gene messages, including several genes involved in extracellular matrix degradation and lipid/steroid metabolism previously reported to be induced by hCG. This screening also identified a group of candidate genes whose ovarian expression and gonadotropin regulation was hitherto unknown. The induction of three of these genes, encoding cutaneous fatty acid-binding protein, the interleukin-4 receptor alpha chain, and prepronociceptin, was confirmed and further characterized by Northern blot analysis. In addition, in situ hybridization analysis showed that hCG administration resulted in exclusive or predominant expression of all three genes in theca cells. These results demonstrate that DNA arrays can be used to identify genes regulated during the periovulatory period, thus contributing to a more detailed understanding of the molecular mechanisms of ovulation.
Design and analysis of a German telephone speech database for phoneme based training (1997)

Based on the Sotscheck text corpus, we developped a new corpus that was specifically optimised for training phoneme-based recognition systems. Particular attention was payed on good coverage of phone transitions. Even though the resulting corpus is only slightly enlarged, it shows an increased phonetic coverage while maintaining a good phonetic balance. Results of phonetic statistical analysis and of experiments for training an allophonebased recognizer are reported here.
The quantity of CD26 on helper T cells correlates with the efficacy of adoptive cancer immunotherapy (TUM2P.1008) (2015)

Abstract Although Th17 cells cause striking tumor eradication upon transfer into mice bearing established melanoma, their translation into the clinic is barred by a lack of FDA-approved cytokines. Consequently, we sought to determine if IL-17-producing CD4+ cells could be enriched from peripheral blood. We found that functional Th17 cells could be isolated from blood, without the need for polarization, by using the surface marker CD26. Excitingly, very few CD26-rich cells, termed CD26high T cells, displayed striking antitumor activity and survival upon transfer into melanoma-bearing mice compared to CD26negative or bulk CD4+ T cells. Of translational significance, we found that human CD26high cells had heightened cytotoxicity and caused greater cancer cell death in vitro. Interestingly, human CD26high T cells have enhanced expression of cytokines (IL-17, IFN-γ, IL-2, TNFα), transcription factors (RORγ, Tbet), integrins (LFA-1, VLA-1) and chemokines (RANTES). Given the unique phenotype of CD26high T cells compared to cells with decreased CD26 expression, the question of this marker's importance is raised. Our preliminary studies reveal that the enzymatic activity of CD26 may be important for the enhanced function, cytotoxicity and migration of these cells and could possibly be targeted to enhance future therapies. Not only do CD26high T cells give hope for Th17 clinical translation, but also provide a potential mechanism by which to improve the T cells used for cancer immunotherapies.
Outage rate regions for the MISO IFC (2009)

We consider the two-user multiple-input single-output (MISO) interference channel (IFC) and assume that the receivers treat the interference as additive Gaussian noise. We study the rates that can be achieved in a slow-fading scenario, allowing an outage probability. We introduce three definitions for the outage region of the IFC. The definitions differ on whether the rates are declared in outage jointly or individually and whether there is perfect or statistical information about the channels. Even for the broadcast and the multiple-access channels, which are special cases of the IFC, there exist several definitions of the outage rate regions. We provide interpretations of the definitions and compare the corresponding regions via numerical simulations. Also, we discuss methods for finding the regions. This includes a characterization of the beamforming strategies, which are optimal in the sense that achieve rate pairs on the Pareto boundary of the outage rate region.
Deep Unsupervised Learning using Nonequilibrium Thermodynamics (2015)

A central problem in machine learning involves modeling complex data-sets using highly flexible families of probability distributions in which learning, sampling, inference, and evaluation are still analytically or computationally tractable. Here, we develop an approach that simultaneously achieves both flexibility and tractability. The essential idea, inspired by non-equilibrium statistical physics, is to systematically and slowly destroy structure in a data distribution through an iterative forward diffusion process. We then learn a reverse diffusion process that restores structure in data, yielding a highly flexible and tractable generative model of the data. This approach allows us to rapidly learn, sample from, and evaluate probabilities in deep generative models with thousands of layers or time steps, as well as to compute conditional and posterior probabilities under the learned model. We additionally release an open source reference implementation of the algorithm.
DSP implementation of sqrt(M)-Best rotated QAM soft-demapper (2014)

In the second generation terrestrial digital video broadcasting (DVB-T2) systems, one of the important features is the usage of rotated quadrature amplitude modulation (QAM) to exploit signal space diversity. However, the implementation of soft-demapper is very challenging and becomes more complex as the modulation order increases. Recently, a √(M)-best soft-demapper was proposed which can achieve the same performance as the full search scheme but with low complexity. In this paper, we implement the √(M)-best soft-demapper on a digital signal processer (DSP) with a coarse-grained reconfigurable array (CGRA) architecture. The best candidate selection algorithm is accordingly modified for friendly implementation. Our results show that the √(M)-best soft-demapper can be implemented with 82% less cycles than the full search based soft-demapper for the most complex 256-QAM case.
Sharp kelvinlets (2019)

In this work, we present an extension of the regularized Kelvinlet technique suited to non-smooth, cusp-like edits. Our approach is based on a novel multi-scale convolution scheme that layers Kelvinlet deformations into a finite but spiky solution, thus offering physically based volume sculpting with sharp falloff profiles. We also show that the Laplacian operator provides a simple and effective way to achieve elastic displacements with fast far-field decay, thereby avoiding the need for multi-scale extrapolation. Finally, we combine the multi-scale convolution and Laplacian machinery to produce Sharp Kelvinlets, a new family of analytic fundamental solutions of linear elasticity with control over both the locality and the spikiness of the brush profile. Closed-form expressions and reference implementation are also provided.
Conformationally Constrained ortho-Anilino Diaryl Ureas: Discovery of 1-(2-(1′-Neopentylspiro[indoline-3,4′-piperidine]-1-yl)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea, a Potent, Selective, and Bioavailable P2Y1 Antagonist (2013)

Preclinical antithrombotic efficacy and bleeding models have demonstrated that P2Y1 antagonists are efficacious as antiplatelet agents and may offer a safety advantage over P2Y12 antagonists in terms of reduced bleeding liabilities. In this article, we describe the structural modification of the tert-butyl phenoxy portion of lead compound 1 and the subsequent discovery of a novel series of conformationally constrained ortho-anilino diaryl ureas. In particular, spiropiperidine indoline-substituted diaryl ureas are described as potent, orally bioavailable small-molecule P2Y1 antagonists with improved activity in functional assays and improved oral bioavailability in rats. Homology modeling and rat PK/PD studies on benchmark compound 3l will also be presented. Compound 3l was our first P2Y1 antagonist to demonstrate a robust oral antithrombotic effect with mild bleeding liability in the rat thrombosis and hemostasis models.