gebhart/patrepeval huggingface dataset:
Echinomycin, a Small-Molecule Inhibitor of Hypoxia-Inducible Factor-1 DNA-Binding Activity (2005)

The identification of small molecules that inhibit the sequence-specific binding of transcription factors to DNA is an attractive approach for regulation of gene expression. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that controls genes involved in glycolysis, angiogenesis, migration, and invasion, all of which are important for tumor progression and metastasis. To identify inhibitors of HIF-1 DNA-binding activity, we expressed truncated HIF-1alpha and HIF-1beta proteins containing the basic-helix-loop-helix and PAS domains. Expressed recombinant HIF-1alpha and HIF-1beta proteins induced a specific DNA-binding activity to a double-stranded oligonucleotide containing a canonical hypoxia-responsive element (HRE). One hundred twenty-eight compounds previously identified in a HIF-1-targeted cell-based high-throughput screen of the National Cancer Institute 140,000 small-molecule library were tested in a 96-well plate ELISA for inhibition of HIF-1 DNA-binding activity. One of the most potent compounds identified, echinomycin (NSC-13502), a small-molecule known to bind DNA in a sequence-specific fashion, was further investigated. Electrophoretic mobility shift assay experiments showed that NSC-13502 inhibited binding of HIF-1alpha and HIF-1beta proteins to a HRE sequence but not binding of the corresponding proteins to activator protein-1 (AP-1) or nuclear factor-kappaB (NF-kappaB) consensus sequences. Interestingly, chromatin immunoprecipitation experiments showed that NSC-13502 specifically inhibited binding of HIF-1 to the HRE sequence contained in the vascular endothelial growth factor (VEGF) promoter but not binding of AP-1 or NF-kappaB to promoter regions of corresponding target genes. Accordingly, NSC-13502 inhibited hypoxic induction of luciferase in U251-HRE cells and VEGF mRNA expression in U251 cells. Our results indicate that it is possible to identify small molecules that inhibit HIF-1 DNA binding to endogenous promoters.
A Multi-Task Learning Model for Estimating Fractional Inspiratory Time from Electrocardiography (2020)

Non-invasive at-home monitoring of lung and lung airways health enables the early detection and tracking of respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD). Various proposed approaches estimate the respiratory rate and extract the respiratory waveform from an electrocardiogram (ECG) signal as a way to discreetly monitor lung health. Unfortunately, these approaches fail to accurately capture the respiratory cycle phase features, resulting in a non-specific, incomplete picture of lung health. This paper introduces an algorithm to extract more respiratory information from the ECG signal by framing the problem as a binary classification task. In addition to respiratory rate (R.R.), the algorithm derives the fractional inspiratory time (F.I.T.), a direct measure of airway obstruction. The algorithm is based on a gated recurrent neural network that infers vital respiratory information from a two-lead ECG signal. We measure our algorithm performance on real data collected in the CEBS database. Our algorithm maintains exceptional performance in estimating the respiratory rate and outperforms current algorithms that extract the respiratory cycle phases and estimate F.I.T. Our algorithm reports a mean squared error (MSE) of 0.0033 in the computation of F.I.T. (values range from 0.2-0.8) and an MSE of 0.72 for respiratory rate (values range from 10 - 30 breaths per minute (bpm)). This performance results in a 91% accuracy in F.I.T. prediction and 97% accuracy in respiratory rate estimation.
Comparative Genomic Analyses of 17 Clinical Isolates of Gardnerella vaginalis Provide Evidence of Multiple Genetically Isolated Clades Consistent with Subspeciation into Genovars (2012)

Gardnerella vaginalis is associated with a spectrum of clinical conditions, suggesting high degrees of genetic heterogeneity among stains. Seventeen G. vaginalis isolates were subjected to a battery of comparative genomic analyses to determine their level of relatedness. For each measure, the degree of difference among the G. vaginalis strains was the highest observed among 23 pathogenic bacterial species for which at least eight genomes are available. Genome sizes ranged from 1.491 to 1.716 Mb; GC contents ranged from 41.18% to 43.40%; and the core genome, consisting of only 746 genes, makes up only 51.6% of each strain's genome on average and accounts for only 27% of the species supragenome. Neighbor-grouping analyses, using both distributed gene possession data and core gene allelic data, each identified two major sets of strains, each of which is composed of two groups. Each of the four groups has its own characteristic genome size, GC ratio, and greatly expanded core gene content, making the genomic diversity of each group within the range for other bacterial species. To test whether these 4 groups corresponded to genetically isolated clades, we inferred the phylogeny of each distributed gene that was present in at least two strains and absent in at least two strains; this analysis identified frequent homologous recombination within groups but not between groups or sets. G. vaginalis appears to include four nonrecombining groups/clades of organisms with distinct gene pools and genomic properties, which may confer distinct ecological properties. Consequently, it may be appropriate to treat these four groups as separate species.
Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers (2021)

Urinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation differed between CSFs and NSFs. Further validation of these and other populations of urinary EVs in larger cohort could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.
Very Rapid, Ionic Strength-Dependent Association and Folding of a Heterodimeric Leucine Zipper (1997)

Leucine zippers (coiled coils) are dimerization motifs found in several DNA-binding transcription factors. A parallel leucine zipper composed of the acidic chain X1-EYQALEKEVAQLEAENX2-ALEKEVAQLEHEG-amide and the basic chain X1-EYQALKKKVAQLKAKNX2ALKKKVAQLKHKG-amide was designed to study the kinetics of folding of a heterodimeric leucine zipper and to investigate the role of electrostatic attraction between oppositely charged peptide chains to the folding reaction. Each peptide alone did not form a leucine zipper at ionic strength (mu) < 1 M because of electrostatic repulsion between like charges in a homodimer. Therefore, the formation of the heterodimeric leucine zipper could be investigated by simple mixing of acidic and basic chains. To monitor folding, a fluorescent label was located either at the N-terminus (X1 = fluorescein-GGG, X2 = Q) or in the center of the coiled coil (X1 = acetyl, X2 = W). Folding could be described by a simple two-state reaction involving the disordered monomers and the folded heterodimer. The same bimolecular rate constant (k(on)) was observed independent of the location of the fluorescent label, indicating that both fluorescence probes monitored the same reaction. Lowering of the ionic strength increased k(on) from 4 x 10(6) M-1 s-1 (mu = 525 mM) to about 5 x 10(7) M-1 s-1 (mu = 74 mM). When extrapolated to mu = O, k(on) was approximately 10(9) M-1 s-1, which is near the diffusion limit. In contrast, the rate of dissociation depended very weakly on ionic strength; k(off) decreased only by about 2-fold when mu was lowered from 525 to 74 mM. Equilibrium association constants (Ka) of the heterodimeric zippers measured directly and calculated from kinetic constants (Ka = k(on)/k(off) were in good agreement. The observed two-state mechanism, the strong dependence on ionic strength of k(on) but not of k(off), and the nearly diffusion-limited association rate at very low ionic strength point to a folding pathway in which the formation of an electrostatically stabilized dimeric intermediate may be rate-limiting and the subsequent folding to the final dimer is very rapid and follows a "down-hill" free energy landscape. The small increase of k(off) at increasing ionic strength indicates a minor contribution of electrostatics to the stability of the folded leucine zipper.
Bis[<i>N</i>-alkyl-<i>N</i><i>N</i>-di(2-pyridylmethyl)amine]zinc(II) perchlorates display <i>cis-facial</i> stereochemistry in solid state and solution (2013)

N-Alkyl-N,N-di(2-pyridylmethyl)amines are ligands commonly used by supramolecular chemists in molecular recognition and sensing applications. The metal coordination complexes of these ligands, in particular those with 2:1 (ligand:metal) molar ratio, have not been sufficiently characterised in solution. In this work, bis[N-alkyl-N,N-di(2-pyridylmethyl)amine]zinc(II) perchlorates are characterised in both solid and solution phases, using X-ray crystallography and NMR spectroscopy, respectively. Only the cis-facial stereoisomer is observed. Density functional theory calculations support the thermodynamic preference for this stereochemistry, as in one representative case the gas phase energy of the cis-facial configuration is lower than those of the trans-facial and meridional configurations by 4.0 and 4.5 kcal/mol, respectively.
Independent and Synergistic Associations of Biomarkers of Vitamin D Status With Risk of Coronary Heart Disease (2017)

Our data suggest that higher 25OHD levels were associated with a lower CHD risk when PTH levels were high, whereas no association was observed for participants with low PTH levels. VDBP but not bioavailable 25OHD was independently associated with lower CHD risk.
Models of bipolar charge transport in polyethylene (2006)

We introduce and develop two bipolar transport models which are based on appreciably different physical assumptions regarding the distribution function in the energy levels of trap states. In the first model, conduction is described by an effective mobility of the carriers and the accumulation of stored space charge is taken into account through a single trapping level. In the second model the hypothesis of an exponential distribution function of trap depth is made, with conduction taking place via a hopping process from site to site. The results of simulations of the two models are compared with experimental data for the external current and the space-time evolution of the electrical space charge distribution. The two descriptions are evaluated in a critical way, and the prospects for these models to adequately describe real systems are given.
Aperiodic artificial substrates for multipole bandpass filters (2007)

Though periodic structures have been the focus of intense research for the past decade, in practice, a truly periodic structure is rarely the proper topology to give a desired or specified transfer function. Traditionally, filtering in periodic substrates was shown by creating defects in an otherwise periodic lattice. However, this approach limits the transfer function of the resulting filter. The use of perturbations in the periodicity in order to create multipole filters with arbitrary transfer functions that are not available inside simple periodic substrates is demonstrated. A methodology is presented to design the aperiodic substrates. Measured and simulated four-pole filter responses are shown for both all-dielectric substrates with high-dielectric-constant titania inclusions and metallodielectric substrates with metallic inclusions inside low-temperature cofired ceramics (LTCC). The measured all-dielectric substrate demonstrates a filter at 21.6 GHz with an insertion loss of 1.69 dB and a narrow bandwidth of only 0.89%, indicating quality factors &gt;1000. Filters with specified Chebyshev transfer functions inside LTCC metallodielectric substrates show consistency within &lt;0.5% at 10.89 GHz due to the mature fabrication process.
CAR T-cell immunotherapy of MET-expressing malignant mesothelioma (2017)

Mesothelioma is an incurable cancer for which effective therapies are required. Aberrant MET expression is prevalent in mesothelioma, although targeting using small molecule-based therapeutics has proven disappointing. Chimeric antigen receptors (CARs) couple the HLA-independent binding of a cell surface target to the delivery of a tailored T-cell activating signal. Here, we evaluated the anti-tumor activity of MET re-targeted CAR T-cells against mesothelioma. Using immunohistochemistry, MET was detected in 67% of malignant pleural mesotheliomas, most frequently of epithelioid or biphasic subtype. The presence of MET did not influence patient survival. Candidate MET-specific CARs were engineered in which a CD28+CD3ζ endodomain was fused to one of 3 peptides derived from the N and K1 domains of hepatocyte growth factor (HGF), which represents the minimum MET binding element present in this growth factor. Using an NIH3T3-based artificial antigen-presenting cell system, we found that all 3 candidate CARs demonstrated high specificity for MET. By contrast, these CARs did not mediate T-cell activation upon engagement of other HGF binding partners, namely CD44v6 or heparan sulfate proteoglycans, including Syndecan-1. NK1-targeted CARs demonstrated broadly similar <i>in vitro</i> potency, indicated by destruction of MET-expressing mesothelioma cell lines, accompanied by cytokine release. <i>In vivo</i> anti-tumor activity was demonstrated following intraperitoneal delivery to mice with an established mesothelioma xenograft. Progressive tumor regression occurred without weight loss or other clinical indicators of toxicity. These data confirm the frequent expression of MET in malignant pleural mesothelioma and demonstrate that this can be targeted effectively and safely using a CAR T-cell immunotherapeutic strategy.
Quantification of vancomycin in human serum by LC-MS/MS (2013)

Employing a closely related homologue molecule for internal standardization and the use of MS/MS following highly efficient sample pre-fractionation by HPLC, the method described here can be considered to offer the highest level of analytical reliability realized so far for the quantification of vancomycin in human serum. Thus, the method is suitable to be used in a comprehensive reference measurement system for vancomycin.
Innenrücktitelbild: Preferential Siting of Aluminum Heteroatoms in the Zeolite Catalyst Al‐SSZ‐70 (Angew. Chem. 19/2019) (2019)

Bevorzugte Positionen und relative Besetzungen von Aluminiumatomen im Aluminosilikat-Zeolith-Katalysator Al-SSZ-70 werden von B. F. Chmelka et al. in ihrer Zuschrift auf S. 6321 bestimmt. Die Adsorptions- und Reaktionseigenschaften des Katalysators hängen stark von der Art und Verteilung der Al-Atome in den nanoporösen Gerüsten ab. Diese Parameter wurden durch eine Kombination von Festkörper-NMR-Spektroskopie und Synchrotron-XRPD-Analysen ermittelt.
I-Centric Communications (2006)

This chapter introduces the rationales, the framework, and the architecture of I-centric Communications, a new paradigm to design and to develop telecommunication systems. I-centric Communications has been proposed by the Wireless World Research Forum (WWRF) working group 2 based on numerous contributions from academia and industry world wide.
4 × 4 vertical-cavity surface-emitting laser (VCSEL) and metal–semiconductor–metal (MSM) optical backplane demonstrator system (1996)

We describe a system demonstrator based on vertical-cavity surface-emitting lasers, metal-semiconductor-metal detectors, printed circuit board (PCB) level optoelectronic device packaging, a compact bulk optical relay, and novel barrel/PCB optomechanics. The entire system was constructed in a standard VME electrical backplane chassis and was capable of operating at >1.7 Gbit/s of aggregate data capacity. In addition to the component technologies developed, we describe operational testing and characterization of the demonstrator.
Numerical Simulation of Freight Railcar Dynamic Clearance Envelopes (2008)

The operating dynamic clearance envelope has historically been a sum of estimated dimensional tolerances, sometimes even called “black magic” [1]. These tolerances exist by design within the car and the track, as well as between the wheel flanges and the rail gage face. Field observations of operating clearance have augmented these estimates. Recently a review of such expectations was desired as related to wide and/or tall payloads, with particular respect to train speed and track roughness. This project reexamines the factors affecting car body envelopes, including track curvature and elevation, and car parameters such as length, center of gravity (CG), and side bearing type. A particular goal of this study was to gain a rough understanding of the behavior expected relative to wide loads in the speed range of 30–50 mph. Both static analyses and dynamic negotiation of typical revenue track have been predicted. The NUCARS® multibody simulation software has been used to examine the influence of operating speed and FRA track class on the dynamic envelope. A summary of results is presented along with a discussion of general guidelines and additional considerations.
A metabolomic study of substantial equivalence of field‐grown genetically modified wheat (2006)

The 'substantial equivalence' of three transgenic wheats expressing additional high-molecular-weight subunit genes and the corresponding parental lines (two lines plus a null transformant) was examined using metabolite profiling of samples grown in replicate field trials on two UK sites (Rothamsted, Hertfordshire and Long Ashton, near Bristol) for 3 years. Multivariate comparison of the proton nuclear magnetic resonance spectra of polar metabolites extracted with deuterated methanol-water showed a stronger influence of site and year than of genotype. Nevertheless, some separation between the transgenic and parental lines was observed, notably between the transgenic line B73-6-1 (which had the highest level of transgene expression) and its parental line L88-6. Comparison of the spectra showed that this separation resulted from increased levels of maltose and/or sucrose in this transgenic line, and that differences in free amino acids were also apparent. More detailed studies of the amino acid composition of material grown in 2000 were carried out using gas chromatography-mass spectrometry. The most noticeable difference was that the samples grown at Rothamsted consistently contained larger amounts of acidic amino acids (glutamic, aspartic) and their amides (glutamine, asparagine). In addition, the related lines, L88-6 and B73-6-1, both contained larger amounts of proline and gamma-aminobutyric acid when grown at Long Ashton than at Rothamsted. The results clearly demonstrate that the environment affects the metabolome and that any differences between the control and transgenic lines are generally within the same range as the differences observed between the control lines grown on different sites and in different years.
Standardization for a Korean Version of Hearing Handicap Inventory for the Elderly (2011)

Background and ObjectivesZZThis study has been performed to determine the reliability and validity of the Korean version of Hearing Handicap Inventory for the Elderly (HHIE), which has been adapted to the Korean population. Subjects and MethodZZFor the Korean version of HHIE (K-HHIE), the processes of independent forward translation, backward translation and reconciliation were standardized using subjects older than 65 years old were recruited from the 10 referral-hospitals. Reliability and validity were evaluated by Cronbach's alpha coefficient, confirmatory factor analysis and testretest analysis. Hearing impairment was assessed using pure tone audiometry, and the result was used as the gold standard. ResultsZZThe recruited K-HHIEs were 169. The reliability of K-HHIE, checked by Cronbach's alpha coefficient, was as high as 0.95. Scale-item correlation coefficient was even higher than 0.97, which shows very high reliability of K-HHIE. Test-retest reliability and the correlation coefficients of social/situational, emotional and total scores of K-HHIE were as high as 0.73, 0.82 and 0.78, respectively. The validity of K-HHIE, checked by confirmatory factor analysis, also showed good construct validity. There was high correlation between hearing level and the scores of K-HHIE, which is another indicative result of its high validity.
Studies on the hydrolytic stability of 2′-fluoroarabinonucleic acid (2′F-ANA) (2009)

The stability of 2'-deoxy-2'-fluoroarabinonucleic acid (2'F-ANA) to hydrolysis under acidic and basic conditions was compared to that of DNA, RNA and 2'F-RNA. In enzyme-free simulated gastric fluid (pH approximately 1.2), 2'F-ANA was found to have dramatically increased stability (virtually no cleavage observed after 2 days) with respect to both DNA (t(1/2) approximately 2 min) and RNA (t(1/2) approximately 3 h (PO) or 3 days (PS)). These results were observed for both phosphodiester and phosphorothioate backbones and with multiple mixed-base sequences. Under basic conditions, 2'F-ANA also showed good stability. In 1 M NaOH at 65 degrees C, 2'F-ANA had a t(1/2) of approximately 20 h, while RNA was entirely degraded in a few minutes. Furthermore, the nuclease cleavage of phosphorothioate 2'F-ANA and DNA by snake venom phosphodiesterase was studied in detail. One diastereomer of the PS-2'F-ANA linkage was found to be much more vulnerable to enzymatic cleavage than the other, which is parallel to the properties observed for PS-DNA. Additional studies of 2'F-ANA-containing oligonucleotides are warranted based on the excellent stability properties described here.
The synthesis, characterization and targeting ability of nano-scale enrichment polymer layers (2013)

Thin polymer films have been utilized as enrichment layers for evanescent waveguide chemical sensors and other analytical techniques. This is due to the fact that the chemical nature of polymers is ideal for trapping chemically similar organic molecules making analysis more convenient. Specifically, research in this area of volatile organic compounds (VOCs) detection, focused has been given to identifying a single polymer film of micron scale thickness to target one analyte. This work focuses on the design and use of multiple polymers in one enrichment layer to target VOCs to facilitate detection. Two distinct layered enrichment systems were synthesized via the “grafting to” approach. The end application is to apply these polymers onto mid-infrared transparent evanescent wave micro-disk or micro-ring resonators. Analysis of the polymer affinity to VOCs and to act as enrichment layers is determined by the thickness increase caused by swelling of the film when exposed to the analyte vapor. Detection analysis was done using attenuated total reflection (ATR) FT-IR spectroscopy. The polymer layered systems were characterized by atomic force microscopy, ellipsometry and infrared spectroscopy. Studies of pure analyte vapors and mixtures were conducted in saturated conditions.
Selected Papers from the First International Conference on Microchannels and Minichannels (2004)

Microchannels and minichannels have received tremendous attention in the last couple of years. Research is being conducted worldwide in traditional heat transfer laboratories as well as in newly fo...