gebhart/patrepeval huggingface dataset:
Parallel β-Sheet Vibrational Couplings Revealed by 2D IR Spectroscopy of an Isotopically Labeled Macrocycle: Quantitative Benchmark for the Interpretation of Amyloid and Protein Infrared Spectra (2012)

Infrared spectroscopy is playing an important role in the elucidation of amyloid fiber formation, but the coupling models that link spectra to structure are not well tested for parallel β-sheets. Using a synthetic macrocycle that enforces a two stranded parallel β-sheet conformation, we measured the lifetimes and frequency for six combinations of doubly (13)C═(18)O labeled amide I modes using 2D IR spectroscopy. The average vibrational lifetime of the isotope labeled residues was 550 fs. The frequencies of the labels ranged from 1585 to 1595 cm(-1), with the largest frequency shift occurring for in-register amino acids. The 2D IR spectra of the coupled isotope labels were calculated from molecular dynamics simulations of a series of macrocycle structures generated from replica exchange dynamics to fully sample the conformational distribution. The models used to simulate the spectra include through-space coupling, through-bond coupling, and local frequency shifts caused by environment electrostatics and hydrogen bonding. The calculated spectra predict the line widths and frequencies nearly quantitatively. Historically, the characteristic features of β-sheet infrared spectra have been attributed to through-space couplings such as transition dipole coupling. We find that frequency shifts of the local carbonyl groups due to nearest neighbor couplings and environmental factors are more important, while the through-space couplings dictate the spectral intensities. As a result, the characteristic absorption spectra empirically used for decades to assign parallel β-sheet secondary structure arises because of a redistribution of oscillator strength, but the through-space couplings do not themselves dramatically alter the frequency distribution of eigenstates much more than already exists in random coil structures. Moreover, solvent exposed residues have amide I bands with >20 cm(-1) line width. Narrower line widths indicate that the amide I backbone is solvent protected inside the macrocycle. This work provides calculated and experimentally verified couplings for parallel β-sheets that can be used in structure-based models to simulate and interpret the infrared spectra of β-sheet containing proteins and protein assemblies, such as amyloid fibers.
A genetic epidemiological study of hereditary prostate cancer (HPC) in Finland: frequent HPCX linkage in families with late-onset disease. (2000)

Several predisposition loci for hereditary prostate cancer (HPC) have been suggested, including HPC1 at 1q24-q25 (OMIM #601518) and HPCX at Xq27-q28 (OMIM #300147). Genetically homogeneous populations, such as that of Finland, and distinct subsets of families may help to minimize the genetic heterogeneity that complicates the genetic dissection of complex traits. Here, the role of the HPC1, and HPCX loci in a series of Finnish prostate cancer families was studied, especially in subgroups of families defined by age, number of affected cases, and the mode of disease transmission. DNA samples were collected from 57 Finnish HPC families with at least two living prostate cancer patients. Linkage analysis was carried out with 39 microsatellite markers for the HPC1 region and 22 markers for the HPCX region. The maximum two-point LOD score for the HPCX was 2.05 (marker DXS1205, at theta = 0.14), whereas HPC1 LOD scores were all negative. In HOMOG3R analyses, significant evidence of heterogeneity was observed. Subgroup analyses performed to explore the nature of this heterogeneity indicated that families with no male-to-male (NMM) transmission and a late age of diagnosis (>65 years) accounted for most of the HPCX-linked cases. The maximum HPCX LOD score in this subgroup was 3.12 (theta = 0.001). Nonparametric sibling pair analyses gave a peak LOD score of 3.04 (P < 0.000093) for the NMM transmission subgroup. No subgroup showed any positivity for HPC1. This study suggests that the HPCX-linked prostate cancer families represent a distinct subgroup characterized by NMM transmission of disease and late age of diagnosis.
Construction of a Physiologically Active Photoaffinity Probe Based on the Structure of Bradykinin: Labelling of Angiotensin Converting Enzyme but Not Candidate Bradykinin Receptors on NG108–15 Cells (1989)

The peptides bradykinin and kallidin are released in response to noxious stimuli and mediate various physiological effects, including a direct stimulation of nociceptive afferent neurones. The nature of the receptor molecules through which these ligands act is presently unknown. We synthesised an iodinatable photoaffinity probe, N epsilon-4-azidosalicylylkallidin, and used it in an attempt to identify candidate bradykinin receptors on the NG108-15 neuroblastoma X glioma hybrid cell line. The ligand bound in subdued light to a particulate fraction of NG108-15 tumours and could be displaced by bradykinin with an IC50 of 0.33 nM. In a physiological assay, it behaved as an agonist equipotent with bradykinin. Gel analysis of the labelled products after photolysis of the iodinated ligand in the presence of NG108-15 cells or tumour membranes revealed bradykinin-blockable labelling of a glycoprotein with an Mr of 166,000. The probe was also able to label purified commercial angiotensin converting enzyme. The band labelled in NG108-15 cells was immunoprecipitable with a polyclonal antiserum to angiotensin converting enzyme, an enzyme shown to be present in low amounts in these preparations by direct binding using the iodinatable specific ligand MK351A.
Monitoring of spinal cord stimulation evoked potentials during thoracoabdominal aneurysm surgery (1991)

Repair of a thoracoabdominal aneurysm involves a significant risk of ischemic injury to the spinal cord. Standard monitoring of somatosensory evoked potentials, which relies upon peripheral nerve stimulation, becomes nonspecific and insensitive during this surgery when aortic cross-clamping produces lower extremity ischemia causing a peripheral conduction block. Techniques for the insertion of percutaneous epidural electrodes, developed originally for pain management, have been adapted to this setting to permit direct stimulation of the spinal cord for intraoperative monitoring of evoked potentials. The clinical outcome in patients monitored by this technique has been consistent with evoked potential findings. (Neurosurgery 28:325-330, 1991)
State-of-the-art and future directions of high-performance all-digital frequency synthesis in nanometer CMOS (2010)

The past several years have successfully brought all-digital techniques to the RF frequency synthesis, which could arguably be considered one of the last strong bastions of the traditionally-analog design approaches. With their high sensitivity and high dynamic range requirements, the RF circuits have long had a good excuse to avoid any possible source of digital switching activity. With the constant scaling of CMOS feature size and the merciless push for integration, the existence of almost free and powerful digital logic could not go unnoticed. Hence, the environment was ripe to transform the RF functions into digital realizations, as well as to apply digital assistance to help with the performance of RF circuits. This paper revisits the digitization journey of the traditional charge-pump PLL and offers a few novel techniques to further improve area, current consumption, testability and reliability of frequency synthesizers.
Social Demarcation and the Forms of Psychological Fracture in Book One of Richard Wright's <i>Native Son</i> (2010)

One of the most stunning aspects of Frederick Douglass's narrative of his experiences as a slave is his keen insight into the psychology of both the slave and the slave owner. Douglass vividly represents the diabolical psychological manipulation of the slaves by the white masters, but he also shows the figures in his work to be so psychologically damaged by the unnatural and unholy master /slave relationship that the owner in such relationships frequently turns bestial or cruel even while maintaining a veneer of civility while the slave obviously suffers a depleted sense of worth and identity; dehumanization is the consequence common to both. Richard Wright's representation of Jim Crow-era Chicago in Native Son depicts a society in logical progression from Douglass's slave era. Though slavery was abolished a generation after the publication of Douglass's narrative, the sociological fractures persisted for generations hence, and enslavement was replaced with economic oppression and geographic racial demarcation, which only continued a long period of existential angst initiated by slavery. Wright's Chicago is fractured both sociologically and geographically, a condition that Wright shows results, like slavery, in the dehumanization of both the privileged and the oppressed both white and black suffer the psychological consequences of an environment schematized by ideas of racial inequity. Wright's central insight in Native Son, however, is that the sociological problem and the psychological one take the same form, a dissociation of parts. He sees the individual damage among AfricanAmericans as a psychological fracturing of identity that reflects and necessarily mimics the fractured society that whites work to maintain and blacks are forced to accept. The lead character of Native Son, Bigger Thomas, struggles with negotiating the different formulations of his identity, which are thrown into disarray by a segregated, inequitable, and frequently hostile society. The
Uniform high bandwidth, high CW power VCSEL arrays (2009)

A high bandwidth, high power, 980 nm vertical-cavity surface-emitting laser (VCSEL) array with 3dB frequency response over 7.5 GHz and continuous wave (CW) power of greater than 120 mW at room temperature is reported.
Transcriptional repression of the human p53 gene by cobalt chloride mimicking hypoxia (2001)

The switch to an angiogenic phenotype is known to be a fundamental determinant of neoplastic growth and tumor progression. We herein report that the transcription of the human p53 gene was repressed by treatment with a hypoxia-mimicking concentration of cobalt chloride and alone by hypoxia-inducible factor 1alpha. Analyses of serial deletions, site-directed mutageneses and heterologous promoter systems showed that the site responsible for the repression by both factors was the E-box element in the promoter of the p53 gene. These results alongside previous data suggest that the loss of p53 including the transcriptional repression may play an important role in the angiogenic switch during tumorigenesis.
New and efficient Synthesis of Nucleoside Polyphosphates and Nucleoside Monophosphate Sugars (2008)

A new and efficient method for the synthesis of nucleoside di- and triphosphates, dinucleoside tetraphosphates and nucleoside monophosphate sugars is described. This new route is based on cycloSal-nucleosyl-phosphate triesters as active ester that underlie fast conversion to the corresponding products.
Quantifying signaling pathway activation to monitor the quality of induced pluripotent stem cells (2015)

Many attempts have been made to evaluate the safety and potency of human induced pluripotent stem cells (iPSCs) for clinical applications using transcriptome data, but results so far have been ambiguous or even contradictory. Here, we characterized stem cells at the pathway level, rather than at the gene level as has been the focus of previous work. We meta-analyzed publically-available gene expression data sets and evaluated signaling and metabolic pathway activation profiles for 20 human embryonic stem cell (ESC) lines, 12 human iPSC lines, five embryonic body lines, and six fibroblast cell lines. We demonstrated the close resemblance of iPSCs with ESCs at the pathway level, and provided examples of how pathway activity can be applied to identify iPSC line abnormalities or to predict in vitro differentiation potential. Our results indicate that pathway activation profiling is a promising strategy for evaluating the safety and potency of iPSC lines in translational medicine applications.
Permeation Equipment for High-Pressure Gas Separation Membranes (2003)

This paper describes the development of a constant volume, variable pressure permeation system for use in testing membrane materials up to pressures of 276 bar with both a vacuum and pressurized downstream. In addition, a membrane masking technique that is well-suited for use with this system in high-pressure applications is also described. To illustrate the utility of the equipment, permeation and selectivity results for a commercially available polyimide, Matrimid, under pure and mixed gas conditions are presented and discussed in relation to studies reported at lower feed pressures with more conventional systems.
Genetic influences of the intercellular adhesion molecule 1 (ICAM‐1) gene polymorphisms in development of Type 1 diabetes and diabetic nephropathy (2006)

The present study provided evidence that SNPs rs281432(C/G) and rs5498 E469K(A/G) in the ICAM-1 gene confer susceptibility to the development of T1D and might also be associated with diabetic nephropathy in Swedish Caucasians.
715 Corticosteroid Sparing Effects of Ustekinumab Therapy in UC Patients: Results From the UNIFI Program (2019)

INTRODUCTION: Ustekinumab (UST), an IL12/23 blocker approved for Crohn's disease, was effective in Phase 3 induction and maintenance studies of patients with moderate-severe ulcerative colitis (UC). Since discontinuation of corticosteroids (CS) is an important goal of therapy in UC, this analysis aims to further describe the CS sparing effects of ustekinumab treatment through Week 44 of the UNIFI trial. METHODS: Responders to UST IV induction entered maintenance and were randomized to UST 90 mg SC (q12wks or q8wks), or PBO. During the induction and maintenance studies, oral CS were not to be initiated or increased beyond baseline. At Week 0 of the maintenance study, a scheduled taper was recommended for all patients receiving CS. CS-free Clinical Response (CSR) and remission (CSRem) rates (at Week 44, and for &gt;90 days prior to Week 44) were calculated for the overall population and for the subset of patients on CS at maintenance baseline. Among the subset of patients on CS at maintenance baseline, the mean prednisone-equivalent (P.Eq) CS dose (mg/day) through Week 44 were calculated as were the rates of subjects who were CS-free at Week 44 and for &gt;90 days prior to Week 44. RESULTS: Overall 50.6% (265/523) of patients in the primary analysis population were receiving CS at maintenance baseline. The proportions of patients who were receiving concomitant CS at maintenance baseline were 52.3%, 47.7%, and 52.3% in the UST q8w, UST q12w and PBO groups, respectively. As detailed in Table 1, in the overall population, CSR and CSRem rates were significantly higher for patients who continued on UST therapy during maintenance compared with placebo. Among the patients who achieved CSR or CSRem at Week 44, the majority achieved these endpoints and eliminated CS use at or up to 90 days prior to Week 44. Similar results were observed in the subset of patients on concomitant CS at maintenance BL. In this group, the mean daily P.Eq CS dose at maintenance BL was approximately 15.0 mg/day for all treatment groups. Mean decrease in average daily P.Eq dose at Wk 44 was more pronounced and the proportion of patients who were CS-free was greater in the UST maintenance arms. CONCLUSION: UST maintenance therapy, with both q8w and q12w dosing regimens, is effective in reducing and eliminating the use of CS in patients with UC; the majority of patients (&gt;90%) who achieved clinical response or clinical remission were able to eliminate corticosteroids.
VAB Sway Investigation (2013)

The Vehicle Assembly Building (VAB) was constructed in the mid-1960s to house the Saturn V moon rocket while it was being assembled. Designed to withstand hurricanes and tropical storms, the V AB has a foundation consisting of 30,000 cubic yards of concrete strengthened by 4,225 steel rods driven 160 feet into limestone bedrock. The goal of the VAB Sway Investigation, which began collecting data in April 201 0 and ended in November 2012, was to quantify the displacement or sway of the VAB as a function of wind loading.
Dichlorobis(1,3-imidazolidine-2-thione-S)cadmium(II) (1998)

The redetermination of the crystal structure of a cadmium(II) complex of 1,3-imidazolidine-2-thione (Imt) coordinated with two molecules of Imt and two Cl− ions, [CdCl2(C3H6N2S)2] has been performed in order to obtain accurate parameters and to study the effects of the metal coordination on the metal-S and C—S bonds in Imt complexes. The CdI—S distances of 2.525 (2) and 2.535 (2) Å in the present tetrahedral complex are significantly longer than the corresponding distances in the AuI and CuII complexes of Imt, but there is no significant difference in the C—S distances of 1.721 (6) and 1.710 (6) Å from that in AuI and CuII complexes. This work represents a significant increase in the quality of the structure of the title compound over the earlier work.
Synthesis of Ring-Fluorinated Porphyrins and Reconstitutional Myoglobins with Their Iron Complexes (1996)

Abstract The total syntheses of monofluoroporphyrin derivatives from monofluoropyrroles and the reconstitution of synthetic heme into sperm-whale myoglobin are described. The heme orientation in a cavity of the protein was determined by 1H and 19F NMR studies. It is noted that a fluoro substituent was found to be a useful probe for studying the heme-protein interaction.
Toward extraction of security requirements from text (2018)

We propose and evaluate an information extraction and analysis framework that combines human intelligent (crowdsourcing) with automated methods to produce improved security and privacy requirements incorporating knowledge from post-deployment artifacts such as breach reports.
Learning to Complement Humans (2020)

A rising vision for AI in the open world centers on the development of systems that can complement humans for perceptual, diagnostic, and reasoning tasks. To date, systems aimed at complementing the skills of people have employed models trained to be as accurate as possible in isolation. We demonstrate how an end-to-end learning strategy can be harnessed to optimize the combined performance of human-machine teams by considering the distinct abilities of people and machines. The goal is to focus machine learning on problem instances that are difficult for humans, while recognizing instances that are difficult for the machine and seeking human input on them. We demonstrate in two real-world domains (scientific discovery and medical diagnosis) that human-machine teams built via these methods outperform the individual performance of machines and people. We then analyze conditions under which this complementarity is strongest, and which training methods amplify it. Taken together, our work provides the first systematic investigation of how machine learning systems can be trained to complement human reasoning.
Nylon-6/Ti3C2Tz MXene Nanocomposites Synthesized by in Situ Ring Opening Polymerization of ε-Caprolactam and Their Water Transport Properties (2019)

Clay-reinforced nylon-6 nanocomposites (NCs)-characterized by the full exfoliation of the nanoreinforcement-were introduced in the marketplace in the 1990s. Herein, we demonstrate, for the first time, that Ti<sub>3</sub>C<sub>2</sub>T <sub>z</sub> MXene can be incorporated into nylon-6 to synthesize melt-processable nanocomposites with excellent water barrier properties (94% reduction in water vapor permeation). To intercalate the ε-caprolactam monomer between the MXene multilayers, the latter were first treated with 12-aminolauric acid, a low-cost, nontoxic, biodegradable, and long shelf life compound. Upon heating to 250 °C, in the presence of 6-aminocaproic acid, in situ polymerization occurred, yielding melt-processable nylon-6/MXene NCs that were, in turn, studied by thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, scanning and transmission electron microscopy, infrared spectroscopy, and dynamic vapor sorption analysis. Using the latter, moisture-sorption isotherms of a neat and a 1.9 vol % NC, at 60 °C, were fit to the Guggenheim, Anderson, and de Boer equation. Solubility, permeation, and diffusion coefficients of water through the NCs were measured as a function of temperature and found to be the lowest ever reported for nylon-6, despite the fact that, at ∼1.9 and 5.0 vol %, the MXene loads were relatively low. This record low diffusivity is ascribed to the very large aspect ratios-500 to 1000-of Ti<sub>3</sub>C<sub>2</sub>T <sub>z</sub> flakes and their dispersion. The water permeation rate is a factor of 5 lower than the best reported in the much more mature nylon/clay field, suggesting lower values can be achieved with further optimization. Lastly infrared spectroscopy spectra of neat and NC samples suggest the surface terminations of the 12-Ti<sub>3</sub>C<sub>2</sub>T <sub>z</sub> flakes bind with nylon-6, limiting water adsorption sites, resulting in reduced solubility in the NC films.
Hundreds of variants clustered in genomic loci and biological pathways affect human height (2010)

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2,3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways ( P=0.016) and that underlie skeletal growth defects ( P &lt; 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of alreadydiscovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways. Â© 2010 Macmillan Publishers Limited. All rights reserved.