gebhart/patrepeval huggingface dataset:
Differentiation of Bifidobacterium longum subspecies longum and infantis by quantitative PCR using functional gene targets (2017)

Background. Members of the genus Bifidobacterium are abundant in the feces of babies during the exclusively-milk-diet period of life. Bifidobacterium longum is reported to be a common member of the infant fecal microbiota. However, B. longum is composed of three subspecies, two of which are represented in the bowel microbiota ( B. longum subsp. longum ; B. longum subsp. infantis ). B. longum subspecies are not differentiated in many studies, so that their prevalence and relative abundances are not accurately known. This may largely be due to difficulty in assigning subspecies identity using DNA sequences of 16S rRNA or tuf genes that are commonly used in bacterial taxonomy. Methods. We developed a qPCR method targeting the sialidase gene (subsp. infantis ) and sugar kinase gene (subsp. longum ) to differentiate the subspecies using specific primers and probes. Specificity of the primers/probes was tested by in silico, pangenomic search, and using DNA from standard cultures of bifidobacterial species. The utility of the method was further examined using DNA from feces that had been collected from infants inhabiting various geographical regions. Results. A pangenomic search of the NCBI genomic database showed that the PCR primers/probes targeted only the respective genes of the two subspecies. The primers/probes showed total specificity when tested against DNA extracted from the gold standard strains (type cultures) of bifidobacterial species detected in infant feces. Use of the qPCR method with DNA extracted from the feces of infants of different ages, delivery method and nutrition, showed that subsp. infantis was detectable (0-32.4% prevalence) in the feces of Australian (n = 90), South-East Asian (n = 24), and Chinese babies (n = 91), but in all cases at low abundance (&lt;0.01-4.6%) compared to subsp. longum (0.1-33.7% abundance; 21.4-100% prevalence). Discussion. Our qPCR method differentiates B. longum subspecies longum and infantis using characteristic functional genes. It can be used as an identification aid for isolates of bifidobacteria, as well as in determining prevalence and abundance of the subspecies in feces. The method should thus be useful in ecological studies of the infant gut microbiota during early life where an understanding of the ecology of bifidobacterial species may be important in developing interventions to promote infant health.
Coherent oscillations of driven rf SQUID metamaterials (2017)

Through experiments and numerical simulations we explore the behavior of rf SQUID (radio frequency superconducting quantum interference device) metamaterials, which show extreme tunability and nonlinearity. The emergent electromagnetic properties of this metamaterial are sensitive to the degree of coherent response of the driven interacting SQUIDs. Coherence suffers in the presence of disorder, which is experimentally found to be mainly due to a dc flux gradient. We demonstrate methods to recover the coherence, specifically by varying the coupling between the SQUID meta-atoms and increasing the temperature or the amplitude of the applied rf flux.
ONC206 has anti-tumorigenic effects in human ovarian cancer cells and in a transgenic mouse model of high-grade serous ovarian cancer. (2022)

ONC206, a dopamine receptor D2 (DRD2) antagonist and imipridone, is a chemically modified derivative of ONC201. Recently, ONC206 and other imipridones were identified as activators of the mitochondrial protease ClpP, inducing downstream pathways that allow them to selectively target cancer cells. Clinical trials showed that ONC201, the first in class imipridone, was well tolerated and exhibited tumor regression in some solid tumors. Our goal was to evaluate the effect of ONC206 on cell proliferation and tumor growth in ovarian cancer cell lines and in a transgenic mouse model of high grade serous ovarian cancer (KpB model). ONC206 was more potent than ONC201 in inhibiting cell proliferation, as evidenced by a 10-fold decrease in IC50 for the SKOV3 and OVCAR5 cell lines. This was accompanied by the results that ONC206 significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, caused cellular stress, and inhibited adhesion and invasion <i>in vitro</i>. Treatment of obese and non-obese KpB mice with ONC206 elevated Bip and ClpP expression and reduced KI67, BCL-XL and DRD2 expression in the ovarian tumors. Our findings demonstrate that ONC206 has anti-tumorigenic effects in ovarian cancer as previously demonstrated by ONC201 but appears to be as well tolerated and more potent. Thus, ONC206 deserves further evaluation in clinical trials.
CD8+ T Lymphocytes Immune Depletion and LAG-3 Overexpression in Hodgkin Lymphoma Tumor Microenvironment Exposed to Anti-PD-1 Immunotherapy (2021)

<i>Background</i>: Resistance to anti-PD-1 remains a considerable clinical challenge for the treatment of patients with classical Hodgkin lymphoma (cHL), and mechanisms of anti-PD-1 resistance remain unknown. This pilot study aims to investigate the tumor microenvironment in patients with cHL relapsing after anti-PD-1. <i>Methods</i>: This study investigated tumor samples of eight patients with cHL, including four patients exposed to anti-PD-1 with a paired longitudinal histological analysis before and after anti-PD-1, and four patients not exposed to anti-PD-1 who served as control for the cellular biological investigations. Fresh cells tumor microenvironment analysis included phenotypic characterization of their T cell surfaces immune checkpoint markers PD-1, PD-L1, ICOS, TIM-3, LAG-3, 41-BB and BTLA. Tumor tissues immunohistochemistry staining included CD30, CD4, CD8, CD68, CD163, PD-L1, PD-1, LAG-3 and TIM-3. <i>Findings</i>: Paired longitudinal tumor tissues analysis in the tumor microenvironment found a CD8+ lymphocytes tumor depletion and an increase of LAG-3 staining after anti-PD-1 exposure. The fresh cells analysis of the tumor microenvironment in patients exposed to anti-PD-1 found CD8+ lymphocyte depletion, with an elevated CD4+/CD8+ lymphocytes ratio (median ratio 9.77 in exposed anti-PD-1 versus 2.39 in not-exposed anti-PD-1 patients; <i>p</i> = 0.0943). On the cell surfaces of CD4+ lymphocytes, the median positive expression of LAG-3 was significantly higher in the samples exposed to anti-PD-1 compared to the controls (15.05 [IQR:17.91-10.65] versus 3.84 [IQR 1.87-6.57]; <i>p</i> = 0.0376). <i>Interpretation</i>: This pilot study proposes hypotheses for understanding the resistance to immunotherapies in patients with Hodgkin lymphoma. Hodgkin lymphoma exposed to anti-PD-1 correlated in tumor microenvironment with an immune depletion of CD8+ T lymphocytes and overexpression of LAG-3 on CD4+ helper T lymphocytes.
The Bitter Taste Receptor TAS2R14 as a Drug Target (2022)

G protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants. Besides human senses like vision and olfaction, taste perception is mostly mediated by GPCRs. Hence, the bitter taste receptor family TAS2R comprises 25 distinct receptors and plays a key role in food acceptance and drug compliance. The TAS2R14 subtype is the most broadly tuned bitter taste receptor, recognizing a range of chemically highly diverse agonists. Besides other tissues, it is expressed in human airway smooth muscle and may represent a novel drug target for airway diseases. Several natural products as well as marketed drugs including flufenamic acid have been identified to activate TAS2R14, but higher potency ligands are needed to investigate the ligand-controlled physiological function and to facilitate the targeted modulate for potential future clinical applications. A combination of structure-based molecular modeling with chemical synthesis and in vitro profiling recently resulted in new flufenamic acid agonists with improved TAS2R14 potency and provided a validated and refined structural model of ligand-TAS2R14 interactions, which can be applied for future drug design projects.
A hybrid MoM/FEM model of coupling to thin-wire structures in complex cavities (2003)

Electromagnetic coupling through a narrow-slot aperture to a region containing a thin-wire structure is computed as a characterization of electromagnetic compatibility and interference (EMC/EMI) issues. Results are presented for coupling through a narrow slot to multiple, thin, straight segments of wire in a cavity. The slot has width and depth and the wires have arbitrary position and orientation within the coupled region. By varying the wires/slot geometries the interaction of the respective resonance structures is examined. Results for a coupled half-space as well as results for a complex cavity enclosure containing multiple thin-wire scatterers are presented. The objective of this work is to compute coupling through a narrow slot to a complex cavity containing thin-wire scatterers with arbitrary position and orientation within the cavity, accounting for slot depth, wall losses, and dielectrics in the slot region. Previously, results have been presented that were limited to half-space coupling. The full wires/slot/cavity coupling is now incorporated into the model.
Direct and Indirect Measurements of Granule Strength (1979)

A method for the direct measurement of compressive strength of a single granule was developed and applied to model spherical granules with different sizes and strengths. A ball mill method was also used for evaluating granule strength for practical purposes. For a series of equal sized granules prepared by the same method, the rate of size reduction by ball-milling varied linearly with the compressive strength of a single granule on log-log plots.
Mutation analysis of the RECQL4 gene in sporadic osteosarcomas (2004)

Osteosarcoma (OS) is the most prevalent malignant tumor among cases of Rothmund-Thomson syndrome (RTS) with germline mutations of the RECQL4 gene, a member of the RecQ helicase family. We investigated the involvement of the RECQL4 gene in the development of OS unrelated to RTS. RECQL4 mRNA was detected in 9 of 9 OS cell lines by Northern blotting and 26 of 26 OS tumors by RT-PCR. Direct sequencing of the entire coding region along with flanking splice junctions and 13 small (< 100 bp) introns in 71 OS tumors revealed 2 sites with a single-base change causing an amino acid change (G1814A for R355Q and C2474T for P441S) and one site with a 6 bp inframe deletion (4837-42delTGCACC for CT857-8del). Identical genotypes were found in corresponding normal tissues in all cases, and the frequency of each allele was not significantly different between OS and control populations. Our data indicate that the RECQL4 gene is not a frequent target for somatic mutations in sporadic OS unrelated to RTS.
Suppression of higher-order modes in aircore microstructure fiber designs (2006)

Modified designs for hollow-core bandgap fibers with suppressed higher-order modes are proposed. Numerical simulations demonstrate that index-matched cladding defects can dramatically increase losses of undesirable modes and leave the fundamental well confined.
Mouse Fkbp8 activity is required to inhibit cell death and establish dorso-ventral patterning in the posterior neural tube (2007)

Neural tube defects (NTDs) are birth defects that can be disabling or lethal and are second in their prevalence after cardiac defects among major human congenital malformations. Spina bifida is a NTD where the spinal cord is dysplastic, and the overlying spinal column is absent. At present, the molecular mechanisms underlying the spinal bifida development are largely unknown. In this study, we present a Fkbp8 mouse mutant that has an isolated and completely penetrant spina bifida, which is folate- and inositol-resistant. Fkbp8 mutants are not embryo lethal, but they display striking features of human spina bifida, including a dysplastic spinal cord, open neural canal and disability. The loss of Fkbp8 leads to increased apoptosis in the posterior neural tube, demonstrating that in vivo FKBP8 inhibits cell death. Gene expression analysis of Fkbp8 mutants revealed a perturbation of expression of neural tube patterning genes, suggesting that endogenous FKBP8 activity establishes dorso-ventral patterning of the neural tube. These studies demonstrate that Fkbp8 is not important for embryo survival, but is essential for spinal neural tube patterning, and to block apoptosis, in the developing neural tube. The mutant Fkbp8 allele is a new experimental model which will be useful in dissecting the pathogenesis of spinal NTDs, and enhance our understanding of the etiology of human NTDs.
NOVEL SPINTRONIC MATERIALS BASED ON FERROMAGNETIC SEMICONDUCTOR CHALCOPYRITES (2004)

Ternary diamond-like compounds in II–IV–V 2 semiconductor system heavily-doped with transition d-element Mn have been recently prepared. The materials grown in both forms — single crystal layers and polycrystalline bulks — exhibit well defined ferromagnetic hysteresis with a saturation behavior in the magnetization curve up to above room temperature. Curie temperatures are of T C =310 K to 320 K for ( Cd 1-x Mn x ) GeP 2 and ( Zn 1-x Mn x ) GeP 2 compounds. The chemical states in the bulk of ZnGeP 2 : Mn and interface of Mn -doped ferromagnetic layer on ZnGeP 2 (001) crystal, have been clarified by electron paramagnetic resonance and in situ photoemission spectroscopy. The as-prepared surface consists of Ge -rich, metallic Mn -compound. In and below the sub-surface region, dilute Mn 2+ species as precursors of the DMS phase exist. Mn 2+ ions are paramagnetic active on Zn 2+ sites in the bulk and show five EPR sets of equidistant peaks. Theoretical band-gap calculation suggests a predominant antiferromagnetic order in stoichiometric ( Cd , Mn ) GeP 2 but the systems with vacancies as ( Cd , V C , Mn ) GeP 2 or ( Cd , Ge , Mn ) GeP 2 are ferromagnetic and energetically stable. These materials are of great promise for room-temperature spintronics applications.
Massive and Martensite Transformations in Sn&ndash;Cd Alloys (1986)

The morphological change of substructures and the shape memory effect associated with the simple hexagonal↔β-Sn structural transformation in Sn-(4.2–5.3) at% Cd alloys have been investigated. The alloys were quenched from a temperature at which the simple hexagonal structure was stable to various temperatures. Their substructures were observed by means of an optical microscope and their crystal structures were identified by means of an X-ray diffractometer. The massive transformation as well as the martensite one takes place as a diffusionless transformation. The massive transformation temperature (Ma) is independent of the solute content, while the martensite transformation temperature (Ms) decreases with increasing solute content. A shape memory effect was observed in Sn–Cd alloys and was remarkable for the specimen quenched below 160 K. The shape-recovery amount of the specimen, which is quenched below the Ms temperature and reveals a massive substructure, is considerably small. These features can be explained well by considering that the massive transformation is diffusionless and is controlled by a thermally activated process. Atoms are considered to move individually in the process of the massive transformation.
High-Risk Sarcoidosis. Current Concepts and Research Imperatives (2017)

Sarcoidosis is a disease with heterogeneous manifestations and outcomes, varying in part on the basis of organ involvement. Specifically, patients with sarcoidosis at risk for poor outcomes include individuals with treatment-resistant pulmonary sarcoidosis, including fibrotic pulmonary disease and pulmonary hypertension, as well as those with cardiac, neurologic, and multiorgan disease. The limited but available data relating to these patients with high-risk sarcoidosis, defined as those patients with presentations requiring medical intervention to avoid progressive disability or premature death, was evaluated as part of the National Heart, Lung, and Blood Institute's workshop to improve understanding of these disease manifestations. In particular, knowledge gaps that preclude a greater understanding of the pathogenesis and management of these severe sarcoidosis clinical phenotypes were identified in the workshop. Research strategies are proposed to address critical knowledge gaps that would further our understanding of these disease manifestations and enhance the care of these patients.
ChemInform Abstract: Carbopeptoids: Peptides and Diketopiperazines Incorporating the Anomeric Centre of Mannopyranose. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Compression of Terawatt Long-Wavelength Laser Pulses Through Backward Raman Amplification (2018)

We propose to compress a high-energy, picosecond long-wave infrared (LWIR) pulse in the plasma using backward Raman amplification (BRA). The apparatus is in a counter-propagating geometry that employs a 3 J, 3 ps CO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> laser pulse as the pump, and a microjoule, broadband femtosecond source as the seed. Simulations show that the amplified pulse can reach ~ 5 TW with a pulse duration of ~ 100 fs. Compared with earlier near-infrared BRA experiments, the proposed configuration uses a significantly shorter pump pulse duration, which may reduce limiting factors such as ion motions and Raman forward scattering. The experiment will be carried out at Accelerator Test Facility at Brookhaven National Laboratory.
Parametric Design Study for a Blown Flapped Wing (2021)

View Video Presentation: https://doi.org/10.2514/6.2021-2871.vid The concept of regional and intra-city mobility using small aircraft, commonly known as Urban Air Mobility (UAM), has rapidly become one of the primary interests in commercial aviation; the idea focuses on passenger travel using small, electric aircraft able to operate in constrained take-off and landing environments of urban and suburban areas. While many of the aircraft developed for this concept have focused on vertical take-off and landing (VTOL) capabilities, it has been demonstrated that fixed-wing aircraft using distributed electric powered lift systems might be able to operate under similarly-constrained environments as short take-off and landing (STOL) aircraft. While powered lift is not a new concept, design and analysis tools remain underdeveloped for this purpose because the data needed to validate such methods does not exist. In this paper, a series of wind tunnel surveys were conducted on several configurations of a quasi-2D blown-flap airfoil to enhance understanding of their performance characteristics and generate the validation data needed for future computational analysis.
Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens (2017)

Emicizumab, a humanised bispecific antibody recognising factors (F) IX/IXa and X/Xa, can accelerate FIXa-catalysed FX activation by bridging FIXa and FX in a manner similar to FVIIIa. However, details of the emicizumab-antigen interactions have not been reported so far. In this study, we first showed by surface plasmon resonance analysis that emicizumab bound FIX, FIXa, FX, and FXa with moderate affinities (K<sub>D</sub> = 1.58, 1.52, 1.85, and 0.978 µM, respectively). We next showed by immunoblotting analysis that emicizumab recognised the antigens' epidermal growth factor (EGF)-like domains. We then performed K<sub>D</sub>-based simulation of equilibrium states in plasma for quantitatively predicting the ways that emicizumab would interact with the antigens. The simulation predicted that only a small part of plasma FIX, FX, and emicizumab would form antigen-bridging FIX-emicizumab-FX ternary complex, of which concentration would form a bell-shaped relationship with emicizumab concentration. The bell-shaped concentration dependency was reproduced by plasma thrombin generation assays, suggesting that the plasma concentration of the ternary complex would correlate with emicizumab's cofactor activity. The simulation also predicted that at 10.0-100 µg/ml of emicizumab-levels shown in a previous study to be clinically effective-the majority of plasma FIX, FX, and emicizumab would exist as monomers. In conclusion, emicizumab binds FIX/FIXa and FX/FXa with micromolar affinities at their EGF-like domains. The K<sub>D</sub>-based simulation predicted that the antigen-bridging ternary complex formed in circulating plasma would correlate with emicizumab's cofactor activity, and the majority of FIX and FX would be free and available for other coagulation reactions.
Clinical Implementation of Comprehensive Strategies to Characterize Cancer Genomes: Opportunities and Challenges (2011)

An increasing number of anticancer therapeutic agents target specific mutant proteins that are expressed by many different tumor types. Recent evidence suggests that the selection of patients whose tumors harbor specific genetic alterations identifies the subset of patients who are most likely to benefit from the use of such agents. As the number of genetic alterations that provide diagnostic and/or therapeutic information increases, the comprehensive characterization of cancer genomes will be necessary to understand the spectrum of distinct genomic alterations in cancer, to identify patients who are likely to respond to particular therapies, and to facilitate the selection of treatment modalities. Rapid developments in new technologies for genomic analysis now provide the means to perform comprehensive analyses of cancer genomes. In this article, we review the current state of cancer genome analysis and discuss the challenges and opportunities necessary to implement these technologies in a clinical setting.
Enantiospecific enzyme-catalysed resolution of novel N,N-disubstituted α-amino acid phenolic ester derivatives using pig liver esterase (2001)

R-Amino acid esters 1, 2 and 3 are novel compounds possessing hypnotic activity. On attempting an asymmetric synthesis of these molecules, racemisation was observed when reacting bis(2-methoxyethyl)amine with α-bromo intermediate 4. In vitro plasma stability studies showed that the R enantiomers had much greater resistance to esterase-mediated degradation than the corresponding S enantiomers. This observation led to the use of commercially available pig liver esterase to prepare 1, 2 and 3 on a multigram scale. The crystal structures of 1 and 2 are reported and confirm R configuration.