gebhart/patrepeval huggingface dataset:
A Chemical Biology View of Bioactive Small Molecules and a Binder‐Based Approach to Connect Biology to Precision Medicines (2018)

A simplistic view of drug discovery is that it begins, most often using “model organisms”, with biological inferences of a disease that suggest the need to interfere with some activity, function or process. An enzyme should be inhibited or a pathogen should be killed. Chemical experimentation yields the desired inhibitor, and clinical investigations then test the underlying hypothesis in humans. If the stars align, an effective drug emerges.

The high cost of testing and low rate of success of this paradigm has led the drug-discovery enterprise to search for new and more effective approaches. In this essay, I explore a concept that focuses on the discovery of compounds that bind targets rather than inhibit a biochemical activity. I present evidence that such ‘binders’ can affect protein activity in under-appreciated ways that have therapeutic potential. This approach is well aligned with a current trend in drug discovery – to exploit insights from human biology in order to select therapeutic targets with greater confidence and to understand the deficiencies of the targets that need correction. The targets emerging from this approach most frequently lack the “simple” activities that drive much of past drug discovery. Compounds are needed that engage these targets in new and challenging ways to elicit the novel activities suggested by human biology, especially enhancing functions of proteins and conferring new (neo) functions to proteins (Figure 1).




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Figure 1


Topographically complex hot spots on proteins can be liganded with suitably shaped, often 3-D small molecules, which results in modulating functions in different ways. Binding alters the dynamic and structural features of proteins, resulting in: 1) novel interactions with other proteins and 2) changes in protein dynamics, stability, turnover rates, and tendency to be chemically modified by cellular enzymes. Each of these under-appreciated effects can have therapeutic consequences. In addition to the common use of binders to inhibit function, they can also restore or enhance function, or even create a new function. Achieving a framework of chemical biology that emulates nature and evolution, where nature evolves and optimizes not so much by losing functions, but by enhancing functions and inventing new ones, promises to unlock potential not only for eliminating disease states but also for enhancing and augmenting states of health and wellness.
Attachment and Rosette Formation by Hyphomicrobia (1981)

The processes of reversible and irreversible sorption of Hyphomicrobium sp. strain ZV580 to solid surfaces was investigated with the use of swarmer cell populations. Various compounds and physical conditions were examined for their effect on the cell-cell interactions which lead to the formation of rosette-like cell aggregates. The monosaccharides galactose and mannose were able to completely inhibit rosette formation. Concanavalin A and chloramphenicol were also able to prevent rosette formation, and both trypsin and pronase caused the disassociation of rosettes. The results indicate that the adhesin is a glycoprotein or a peptido-polysaccharide and that the flagellum may act as a vehicle for the transport of this adhesin from the cell to a surface.
T‐Helper 2 Type Cytokine and Soluble Interleukin‐2 Receptor Levels in Seminal Plasma of Infertile Men (1997)

These findings show: a) a lack of IL-4 in seminal plasma; b) similar SIL-2R levels in fertile and infertile seminal plasma; c) increased IL-6 secretion in seminal plasma of infertile subjects; and d) specific correlations of IL-6 with the main semen parameters.
A Method for Exploiting Redundancy to Accommodate Actuator Limits in Multivariable Systems. (1995)

This paper introduces a new method for accommodating actuator saturation in a multivariable system with actuator redundancy. Actuator saturation can cause significant deterioration in control system performance because unmet demand may result in sluggish transients and oscillations in response to setpoint changes. To help compensate for this problem, a technique has been developed which takes advantage of redundancy in multivariable systems to redistribute the unmet control demand over the remaining useful effectors. This method is not a redesign procedure, rather it modifies commands to the unlimited effectors to compensate for those which are limited, thereby exploiting the built-in redundancy. The original commands are modified by the increments due to unmet demand, but when a saturated effector comes off its limit, the incremental commands disappear and the original unmodified controller remains intact. This scheme provides a smooth transition between saturated and unsaturated modes as it divides up the unmet requirement over any available actuators. This way, if there is sufficiently redundant control authority, performance can be maintained.
Handbook of Polypropylene and Polypropylene Composites (1999)

Growth in polypropylene usage as a cost effective replacement of engineering polymers polypropylene - structure, properties, applications chemical coupling agents for filled and GR-PP composites stabilization of flame retarded polypropylene effects of processing and microstructuring in recycled polypropylene and its blends impact behaviour of polypropylene, its blends and composites plastomers as polypropylene impact modifiers talc filled polypropylene glass fibre reinforced polypropylene functionalization of polypropylene using twin screw extruders engineered interphases in polypropylene composites mega-coupled polypropylene composites of glass fibres characterization of long term creep-fatigue behaviour for glass reinforced polypropylene.
Abstract 18218: Prevalence And Significance of a Right Bundle Branch Block in Patients Without Cardiovascular Disease Undergoing an Exercise Stress Test (2017)

Introduction: Right bundle branch block (RBBB) occurs in 0.2% to 1.3% of the general population and was thought to be an incidental finding; however, current conflicting studies demonstrate that th...
Characterization of individual interface traps with charge pumping (1996)

Charge pumping (CP) of individual interface traps has been studied in small field effect transistors. The amplitude of the CP current is found to be quantized in units of qf, where f is the frequency of the applied CP wave form, and each unit represents the response of a single trap. The time dependence for emission of a trapped electron from a single interface trap has also been measured with CP. The emission probability is found to increase exponentially with time, consistent with Shockley–Read–Hall statistics. We also compare the relative merits of random telegraph noise experiments and CP for characterizing individual interface traps.
Immunologic characterization of the tumor-specific bcr-abl junction in Philadelphia chromosome-positive acute lymphoblastic leukemia (1990)

Philadelphia (Ph′)-positive acute lymphoblastic leukemia (ALL) is highly associated with two forms of chimeric bcr-abl proteins: P190bcr- abl and P210bcr-abl. Whereas P210bcr-abl also occurs in chronic myeloid leukemia, P190bcr-abl is uniquely expressed in Ph′-positive ALL. As a consequence, P190bcr-abl is preeminently a tumor-specific marker in leukemic cells of ALL patients. Because P190bcr-abl is composed of the normal bcr and abl proteins, the major part of the P190bcr-abl molecule comprises nontumor-specific determinants. The joining region between bcr and abl, newly generated during the Ph′ translocation, is exclusively a tumor-specific epitope on the P190bcr-abl molecule. Therefore, only antibodies against the bcr-abl joining region will detect the tumor-specificity of P190bcr-abl. In this study a polyclonal antiserum, termed BP-ALL, was raised against a synthetic peptide corresponding to the bcr-abl junction in P190bcr-abl. The reactivity of BP-ALL with native P190bcr-abl derived from a Ph′-positive ALL cell line (TOM-1) was tested using immunoprecipitation analysis. BP-ALL reacted highly specifically with P190bcr-abl but not with P210bcr-abl isolated from chronic myeloid leukemia cell lines. Peptide inhibition studies further confirmed the fine specificity of BP-ALL. Our data indicate that the tumor-specific bcr-abl junction domain is exposed in an antigenic fashion on the P190bcr-abl molecule.
Uracil-tegafur and tamoxifen vs cyclophosphamide, methotrexate, fluorouracil, and tamoxifen in post-operative adjuvant therapy for stage I, II, or IIIA lymph node-positive breast cancer: a comparative study (2009)

UFT administered in combination with TAM holds promise in the treatment of lymph node-positive early breast cancer. On stratified analysis, the recurrence rate in the UFT group was found to be better in oestrogen receptor (ER)-positive patients. Tegafur-based treatment should be evaluated by a prospective randomised trial conducted in ER-positive patients.
ChemInform Abstract: GROUP VI METAL CARBONYL DERIVATES OF UNSYMMETRICAL BIS TERTIARY PHOSPHINE LIGANDS (1973)

Abstract Durch Umsetzung der tert. Diphosphine mit entsprechenden Metallhexacarbo nylen in Diglyme sowie mit Anilinpentacarbonyl‐W in Benzol werden abhängi vom stöchiometrischen Reaktantenverhältnis die Chelat‐Komplexe (I) oder die Zweikernkomplexe (II) bzw. die Pentacarbonyl‐W‐Derivate (III) oder (II) erhalten.
Conductance Fluctuations and Domain Depinning in Quasi-2D Charge-Density-Wave 1T-TaS$_2$ Thin Films (2023)

We investigated the temperature dependence of the conductance fluctuations in thin films of the quasi-two-dimensional 1T-TaS$_2$ van der Waals material. The conductance fluctuations, determined from the derivative current-voltage characteristics of two-terminal 1T-TaS$_2$ devices, appear prominently at the electric fields that correspond to the transitions between various charge-density-wave macroscopic quantum condensate phases and at the onset of the depinning of the charge density wave domains. The depinning threshold field, $E_D$, monotonically increases with decreasing temperature within the nearly commensurate charge-density-wave phase. The $E_D$ value increases with the decreasing 1T-TaS$_2$ film thickness, revealing the surface pinning of the charge density waves. Our analysis suggests that depinning is absent in the commensurate phase. It is induced by the electric field but facilitated by local heating. The measured trends for $E_D$ of the domain depinning are important for understanding the physics of charge density waves in quasi-two-dimensional crystals and for developing electronic devices based on this type of quantum materials.
Empirical analysis of CK metrics for object-oriented design complexity: implications for software defects (2003)

To produce high quality object-oriented (OO) applications, a strong emphasis on design aspects, especially during the early phases of software development, is necessary. Design metrics play an important role in helping developers understand design aspects of software and, hence, improve software quality and developer productivity. In this paper, we provide empirical evidence supporting the role of OO design complexity metrics, specifically a subset of the Chidamber and Kemerer (1991, 1994) suite (CK metrics), in determining software defects. Our results, based on industry data from software developed in two popular programming languages used in OO development, indicate that, even after controlling for the size of the software, these metrics are significantly associated with defects. In addition, we find that the effects of these metrics on defects vary across the samples from two programming languages-C++ and Java. We believe that these results have significant implications for designing high-quality software products using the OO approach.
<i>ADRB2</i> Polymorphisms and Asthma Susceptibility: Transmission Disequilibrium Test and Meta-Analysis (2004)

Our data indicate that ADRB2 does not contribute substantially to susceptibility to asthma, but it is possible that these polymorphisms influence disease activity and drug responses in individuals with asthma.
Reduced Functional Connectivity Between the Hypothalamus and High‐order Cortical Regions in Adolescent Patients With Irritable Bowel Syndrome (2017)

The hypothalamus plays a critical role in maintaining visceral homeostasis. Altered hypothalamus activation has been implicated in functional gastrointestinal disorders, including irritable bowel syndrome (IBS). One important aspect of homeostatic regulation is the cortical modulation of limbic and paralimbic subsystems, including the hypothalamus, which in turn affects the descending regulatory processes mediating visceral homeostasis. Using neuroimaging, we evaluated hypothalamus functional connectivity in adolescent patients with IBS and age-matched healthy controls who received rectal distension stimulations. More extensive hypothalamus connectivity was observed in liminal than subliminal condition in controls, but not in patients with IBS. Compared with controls, patients with IBS showed significantly reduced hypothalamus connectivity in the bilateral prefrontal cortices, supplementary motor and premotor areas, bilateral sensorimotor cortex, and limbic subareas, which are specifically involved in homeostatic regulation. The findings support the generalized homeostatic regulation model that reduced cortical and limbic modulations of hypothalamus functioning underlies disrupted visceral homeostasis in patients with IBS.
MANAGEMENT OF ENDOCRINE DISEASE: Risk of overtreatment in patients with adrenal insufficiency: current and emerging aspects (2017)

The effects of long-term replacement therapy of adrenal insufficiency (AI) are still a matter of controversy. In fact, the established glucocorticoid replacement regimens do not completely reproduce the endogenous hormonal production and the monitoring of AI treatment may be a challenge for the lack of reliable clinical and biochemical markers. Consequently, several AI patients are frequently exposed to relative glucocorticoid excess potentially leading to develop chronic complications, such as diabetes mellitus, dyslipidemia, hypertension and fragility fractures with consequent impaired QoL and increased mortality risk. This review deals with the pathophysiological and clinical aspects concerning the over-replacement therapy of primary and secondary AI.
Validation of International Classification of Diseases criteria to identify severe influenza hospitalizations (2022)

In this cohort study of hospitalized patients with linked medical record data, we developed International Classification of Diseases (ICD) criteria that accurately identified laboratory-confirmed, severe influenza hospitalizations (positive predictive value [PPV] 80%, 95% confidence interval [CI] 71-87%), which we validated through medical record documentation. These criteria identify patients with clinically important influenza illness outcomes to inform evaluation of preventive and therapeutic interventions and public health policy recommendations.
Pathogenesis of fungal disease (2017)

Abstract The pathogenesis of fungal disease involves an interplay between fungal virulence factors and host immune responses. Most fungal pathogens are opportunists that preferentially invade hosts with immune defects, but the fact that relative pathogenicity varies between fungal species (and even between different strains within a species) is evidence that fungi have evolved multiple, different molecular virulence factors. Experiments in which genes encoding putative virulence attributes are specifically disrupted and the resulting mutants are tested for virulence in a range of vertebrate and invertebrate hosts have identified or confirmed many gene products as significant for the pathogenesis of various types of fungal disease. These include factors determining fungal shape in vivo, biofilm formation, and a plethora of surface components, including adhesins and hydrolytic enzymes. This chapter provides an overview of fungal virulence attributes.
Parallel Simulation of NEPs on Clusters (2011)

This paper compares two different approaches, followed by our research group, to efficiently run NEPs on parallel platforms, as general and transparent as possible. The vague results of jNEP (our multithreaded Java simulator for multicore desktop computers) suggests the use of massively parallel platforms (clusters of computers). The good results obtained show the scalability and viability of this last approach.
Tobacco MAP Kinase: A Possible Mediator in Wound Signal Transduction Pathways (1995)

A complementary DNA encoding a mitogen-activated protein (MAP) kinase homolog has been isolated from tobacco plants. Transcripts of the corresponding gene were not observed in healthy tobacco leaves but began to accumulate 1 minute after mechanical wounding. In tobacco plants transformed with the cloned complementary DNA, trans inactivation of the endogenous homologous gene occurred, and both production of wound-induced jasmonic acid and accumulation of wound-inducible gene transcripts were inhibited. In contrast, the levels of salicylic acid and transcripts for pathogen-inducible, acidic pathogenesis-related proteins were increased upon wounding. These results indicate that this MAP kinase is part of the initial response of higher plants to mechanical wounding.
Isolation of Salmonella Species from Ratites (1995)

268 Brief communications2. Gast RK: 1993, Recovery of Salmonella enteritidis from inoc- 5. Kim CJ, Emery DA, Rinke H, et al.: 1989, Effect of time andulated pools of egg contents. J Food Prot 56:21-24. temperature on growth of Salmonella enteritidis in experimen-3. Humphrey TJ, Whitehead A, Gawler AHL, et al.: 1991, Num- tally inoculated eggs. Avian Dis 33:735-742.bers of Salmonella enteritidis in the contents of naturally con-6. St. Louis ME, Morse DL, Potter ME, et al.: 1989, The emergencetaminated hens’ eggs. Epidemiol Infect 106:489-496. of grade A eggs as a major source of Salmonella enteritidis in-4. Keller LH, Benson CE, Garcia V, et al.: 1993, Monoclonal an- fections: new implications for the control of salmonellosis. J Amtibody-based detection system for Salmonella enteritidis. Avian Med Assoc 259:2103-2107.Dis 37:501-507.J Vet Diagn Invest 7:268-269 (1995)
Hardware-Based Linear Program Decoding with the Alternating Direction\n Method of Multipliers (2016)

We present a hardware-based implementation of Linear Program (LP) decoding\nfor binary linear codes. LP decoding frames error-correction as an optimization\nproblem. In contrast, variants of Belief Propagation (BP) decoding frame\nerror-correction as a problem of graphical inference. LP decoding has several\nadvantages over BP-based methods, including convergence guarantees and better\nerror-rate performance in high-reliability channels. The latter makes LP\ndecoding attractive for optical transport and storage applications. However, LP\ndecoding, when implemented with general solvers, does not scale to large\nblocklengths and is not suitable for a parallelized implementation in hardware.\nIt has been recently shown that the Alternating Direction Method of Multipliers\n(ADMM) can be applied to decompose the LP decoding problem. The result is a\nmessage-passing algorithm with a structure very similar to BP. We present new\nintuition for this decoding algorithm as well as for its major computational\nprimitive: projection onto the parity polytope. Furthermore, we present results\nfor a fixed-point Verilog implementation of ADMM-LP decoding. This\nimplementation targets a Field-Programmable Gate Array (FPGA) platform to\nevaluate error-rate performance and estimate resource usage. We show that Frame\nError Rate (FER) performance well within 0.5dB of double-precision\nimplementations is possible with 10-bit messages. Finally, we outline a number\nof research opportunities that should be explored en-route to the realization\nof an Application Specific Integrated Circuit (ASIC) implementation capable of\ngigabit per second throughput.\n
Evaluation of clinical characteristics, diagnostic test results, and outcome in horses with internal infection caused by Corynebacterium pseudotuberculosis: 30 cases (1995–2003) (2005)

Early diagnosis and long-term antimicrobial treatment were important for a successful outcome in horses with internal C. pseudotuberculosis infection. Ultrasonographic imaging was an important technique for identifying specific organs affected, aiding in obtaining samples for a definitive diagnosis, and monitoring response to treatment. Pregnant mares with internal infections are at risk for fetal loss. Preexisting chronic organ disease may be associated with a poor prognosis.
Identification of Nonlinear Viscoelastic Models of Flexible Polyurethane Foam From Uniaxial Compression Data (2015)

Flexible polyethylene foam is used in many engineering applications. It exhibits nonlinear and viscoelastic behavior which makes it difficult to model. To date, several models have been developed to characterize the complex behavior of foams. These attempts include the computationally intensive microstructural models to continuum models that capture the macroscale behavior of the foam materials. In this research, a nonlinear viscoelastic model, which is an extension to previously developed models, is proposed and its ability to capture foam response in uniaxial compression is investigated. It is hypothesized that total stress can be decomposed into the sum of a nonlinear elastic component, modeled by a higher-order polynomial, and a nonlinear hereditary type viscoelastic component. System identification procedures were developed to estimate the model parameters using uniaxial cyclic compression data from experiments conducted at six different rates. The estimated model parameters for individual tests were used to develop a model with parameters that are a function of strain rates. The parameter estimation technique was modified to also develop a comprehensive model which captures the uniaxial behavior of all six tests. The performance of this model was compared to that of other nonlinear viscoelastic models.
Dengue viremia kinetics in asymptomatic and symptomatic infection (2020)

DENV level and kinetics in asymptomatic individuals differed significantly from those of symptomatic cases. Despite the lower viremia, the slower decay rate in asymptomatic infections could lead to their prolonging the infectious reservoir. The improvement of transmission control to prevent such long-lived asymptomatic infections from transmitting the DENV is needed.
Principles of nanoparticle imaging using surface plasmons (2015)

Unlike surface plasmon resonance sensors that detect integral changes to the optical properties of a sample, surface plasmon polariton-microscopy techniques can detect isolated nanoparticles in real-time through their plasmonic image, even of sub-wavelength dimensions. The feature characteristics and intensity of this plasmonic image are dependent on the nanoparticleʼs chemical composition and size. However, the lack of a theoretical model describing the principles forming a plasmonic image have hindered their understanding. In this article, we present a full-wave analytical model that describes electromagnetically the formation of the plasmonic image. Through our analytical model and numerical calculations, we show the properties of a plasmonic image from sub-wavelength to macroscopic particles of various chemical compositions.