gebhart/patrepeval huggingface dataset:
Toll-like Receptor 5 Agonism Protects Mice from Radiation Pneumonitis and Pulmonary Fibrosis (2012)

Radiation pneumonitis and pulmonary fibrosis are the main complications with radiotherapy for thoracic neoplasms, directly limiting the efficient dose in clinical application and currently there are few medicines that effectively function as radioprotectants. However, a TLR5 agonist, CBLB502, was confirmed to have protective efficacy against hematopoietic and gastrointestinal radiation syndromes in mice and primates. This study points to a new direction for protection against thoracic radiation-induced pulmonary syndromes and skin injury by CBLB502. We utilized the TUNEL assay, pathological analysis and immunohistochemistry to obtain evidence that CBLB502 could alleviate the occurrence of radiation pneumonitis and pulmonary fibrosis as well as radiation- induced skin injury. It may thus play a promising role in facilitating clinical radiotherapy of thoracic neoplasms.
Enhancement of Tumor Necrosis Factor-α-Induced Growth Inhibition by Insulin-Like Growth Factor-Binding Protein-5 (IGFBP-5), But Not IGFBP-3 in Human Breast Cancer Cells (2005)

Expression of IGF-binding protein-3 (IGFBP-3) and IGFBP-5 in human breast cancer cells induces apoptosis and is associated with modulations in Bcl-2 proteins, suggesting that these IGFBPs induce an intrinsic apoptotic pathway. In this study we demonstrate that although both IGFBPs induced the activation of caspase-8 and caspase-9, the expression of IGFBP-5, but not IGFBP-3, sensitized MDA-MB-231 breast cancer cells to the inhibitory effects of TNFalpha. This sensitivity to TNFalpha was associated with a block in nuclear factor-kappaB-mediated cell survival signals. IGFBP-5 expression was also associated with a caspase-8-independent activation of Bid, increased levels of cytosolic second mitochondria-derived activator of caspase (Smac)/direct inhibitor of apoptosis proteins (IAP) binding protein with low pI (DIABLO), and an enhanced phosphorylation of c-Jun N-terminal kinase, both basally and in response to TNFalpha. These results suggest that IGFBP-5 expression may influence extrinsic apoptotic pathways via a differential modulation of downstream cell survival and cell death pathways. Furthermore, although IGFBP-3 and IGFBP-5 share much structural and functional homology, they can modulate distinct apoptotic pathways in human breast cancer cells.
Potential GABA B Receptor Antagonists. X The Synthesis of Further Analogues of Baclofen, Phaclofen and Saclofen (1997)

In an attempt to obtain new compounds with binding activity at the GABAB receptor site, we report the synthesis of 3-amino-2-arylpropanoic acids, and the sulfonic, phosphonic and hydroxamic acid analogues. In addition, we report the synthesis of the isomer of phaclofen, 3-amino-1-(4-chlorophenyl)-propylphosphonic acid, and the higher homologue of baclofen, 5-amino-2-(4-chlorophenyl)pentanoic acid.
Effects of practicing tandem gait with and without vibrotactile biofeedback in subjects with unilateral vestibular loss (2008)

Subjects with unilateral vestibular loss exhibit motor control impairments as shown by body and limb deviation during gait. Biofeedback devices have been shown to improve stance postural control, especially when sensory information is limited by environmental conditions or pathologies such as unilateral vestibular loss. However, the extent to which biofeedback could improve motor performance or learning while practicing a dynamic task such as narrow gait is still unknown. In this cross-over design study, 9 unilateral vestibular loss subjects practiced narrow gait with and without wearing a trunk-tilt, biofeedback device in 2 practice sessions. The biofeedback device informed the subjects of their medial-lateral angular tilt and tilt velocity during gait via vibration of the trunk. From motion analysis and tilt data, the performance of the subjects practicing tandem gait were compared over time with and without biofeedback. By practicing tandem gait, subjects reduced their trunk-tilt, center of mass displacement, medial-lateral feet distance, and frequency of stepping error. In both groups, use of tactile biofeedback consistently increased postural stability during tandem gait, beyond the effects of practice alone. However, one single session of practice with biofeedback did not result in conclusive short-term after-effects consistent with short-term retention of motor performance without this additional biofeedback. Results from this study support the hypothesis that tactile biofeedback acts similar to natural sensory feedback to improve dynamic motor performance but does not facilitate a recalibration of motor performance to improve function after short-term use.
<title>Efficiency issues related to probability density function comparison</title> (1996)

The CANDID project (comparison algorithm for navigating digital image databases) employs probability density functions (PDFs) of localized feature information to represent the content of an image for search and retrieval purposes. A similarity measure between PDFs is used to identify database images that are similar to a user-provided query image. Unfortunately, signature comparison involving PDFs is a very time-consuming operation. In this paper, we look into some efficiency considerations when working with PDFs. Since PDFs can take on many forms, we look into tradeoffs between accurate representation and efficiency of manipulation for several data sets. In particular, we typically represent each PDF as a Gaussian mixture (e.g. as a weighted sum of Gaussian kernels) in the feature space. We find that by constraining all Gaussian kernels to have principal axes that are aligned to the natural axes of the feature space, computations involving these PDFs are simplified. We can also constrain the Gaussian kernels to be hyperspherical rather than hyperellipsoidal, simplifying computations even further, and yielding an order of magnitude speedup in signature comparison. This paper illustrates the tradeoffs encountered when using these constraints.
Topological modeling of human anatomy using medical data (2002)

Medical imaging can provide data for useful views of the interior details of human anatomy. In addition to visualization, which in general has been the primary reason for obtaining these data, many other uses are possible. These include modeling of different elements and their inter-relationships-topological modeling, simulation of physical processes, analysis of movements and validation of models. Here, we describe some of the modeling issues from medical imaging. The issues are particularly related to topological modeling of different anatomical elements: bones, muscles, articulations, etc. A 3D topological modeler is presented with which anatomists and other users can build a topological data base containing structural, topological, and mechanical information of anatomical elements.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Intraocular Adenosine Levels in Normal and Ocular-Hypertensive Patients (2003)

These results demonstrate that in ocular hypertensive individuals, aqueous adenosine concentration is correlated with IOP. As the activation of adenosine receptors can modulate IOP and retinal blood flow, adenosine release during periods of ocular hypertension may play an important role in the physiological responses to elevated IOP.
Influenza C virus esterase: analysis of catalytic site, inhibition, and possible function (1989)

The active site serine of the acetylesterase of influenza C virus was localized to amino acid 71 of the hemagglutinin-esterase protein by affinity labeling with 3H-labeled diisopropylfluorophosphate. This serine and the adjacent amino acids (Phe-Gly-Asp-Ser) are part of a consensus sequence motif found in serine hydrolases. Since comparative analysis failed to reveal esterase sequence similarities with other serine hydrolases, we suggest that this viral enzyme is a serine hydrolase constituting a new family of serine esterases. Furthermore, we found that the influenza C virus esterase was inhibited by isocoumarin derivatives, with 3,4-dichloroisocoumarin being the most potent inhibitor. Addition of this compound prevented elution of influenza C virus from erythrocytes and inhibited virus infectivity, possibly through inhibition of virus entry into cells.
HETEROCYCLIC SYNTHESIS WITH ISOTHIOCYANATE AND SULFUR: A NOVEL ROUTE FOR THE SYNTHESIS OF PYRIDINO[2,3-d]THIAZOLE, THIAZOLO[4′,5′:2,3] PYRIDINO[4,3-d]PYRIDAZINE AND THIAZOLO[4,5-b]ISOQUINOLINE DERIVATIVES (1995)

Abstract The reaction of phenyl isothiocyanate and sulfur with the Knovenagel condensated adducts la-e afforded the pyridino[2,3-d]thiazole derivatives 3a-e. The latter compounds proved to be versatile starting materials for the synthesis of polyfunctionally substituted thiazolo[4′,5′:2,3]pyridino[4,3-d]pyridazine and thiazolo[4,5-b)isoquinoline derivatives. Chemical and spectroscopic evidence for the structures of the new compounds, along with a sequence leading to their formation is described.
Enantioselective Responses to a Phosphorothioate Analogue of Lysophosphatidic Acid with LPA3Receptor-Selective Agonist Activity (2003)

The metabolically stabilized LPA analogue, 1-oleoyl-2-O-methyl-rac-glycerophosphothioate (OMPT), is a potent agonist for the LPA(3) G-protein-coupled receptor. A new enantiospecific synthesis of both (2R)-OMPT and (2S)-OMPT is described. Calcium release assays in both LPA(3)-transfected insect Sf9 and rat hepatoma Rh7777 cells showed that (2S)-OMPT was 5- to 20-fold more active than (2R)-OMPT. Similar results were found for calcium release, MAPK and Akt activation, and IL-6 release in human OVCAR3 ovarian cancer cells.
Four-dimensional blood flow-specific markers of LV dysfunction in dilated cardiomyopathy (2012)

Despite equivalent LVSVs, HF patients with mild LV remodelling demonstrate altered diastolic flow routes through the LV and impaired preservation of inflow KE at pre-systole compared with healthy subjects. These unique flow-specific changes in the flow route and energetics are detectable despite clinical compensation, and may prove useful as subclinical markers of LV dysfunction.
5-Chlorothiophene-2-carboxylic Acid [(S)-2-[2-Methyl-3-(2-oxopyrrolidin-1-yl)benzenesulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amide (SAR107375), a Selective and Potent Orally Active Dual Thrombin and Factor Xa Inhibitor (2013)

Compound 15 (SAR107375), a novel potent dual thrombin and factor Xa inhibitor resulted from a rational optimization process. Starting from compound 14, with low factor Xa and modest anti-thrombin inhibitory activities (IC50's of 3.5 and 0.39 μM, respectively), both activities were considerably improved, notably through the incorporation of a neutral chlorothiophene P1 fragment and tuning of P2 and P3-P4 fragments. Final optimization of metabolic stability with microsomes led to the identification of 15, which displays strong activity in vitro vs factor Xa and thrombin (with Ki's of 1 and 8 nM, respectively). In addition 15 presents good selectivity versus related serine proteases (roughly 300-fold), including trypsin (1000-fold), and is very active (0.39 μM) in the thrombin generation time (TGT) coagulation assay in human platelet rich plasma (PRP). Potent in vivo activity in a rat model of venous thrombosis following iv and, more importantly, po administration was also observed (ED50 of 0.07 and 2.8 mg/kg, respectively). Bleeding liability was reduced in the rat wire coil model, more relevant to arterial thrombosis, with 15 (blood loss increase of 2-fold relative to the ED80 value) compared to rivaroxaban 2 and dabigatran etexilate 1a.
Paramagnetic Lipid-Coated Silica Nanoparticles with a Fluorescent Quantum Dot Core: A New Contrast Agent Platform for Multimodality Imaging (2008)

Silica particles as a nanoparticulate carrier material for contrast agents have received considerable attention the past few years, since the material holds great promise for biomedical applications. A key feature for successful application of this material in vivo is biocompatibility, which may be significantly improved by appropriate surface modification. In this study, we report a novel strategy to coat silica particles with a dense monolayer of paramagnetic and PEGylated lipids. The silica nanoparticles carry a quantum dot in their center and are made target-specific by the conjugation of multiple alphavbeta3-integrin-specific RGD-peptides. We demonstrate their specific uptake by endothelial cells in vitro using fluorescence microscopy, quantitative fluorescence imaging, and magnetic resonance imaging. The lipid-coated silica particles introduced here represent a new platform for nanoparticulate multimodality contrast agents.
Encoding Time Series as Images for Visual Inspection and Classification Using Tiled Convolutional Neural Networks (2015)

Inspired by recent successes of deep learning in computer vision and speech recognition, we propose a novel framework to encode time series data as different types of images, namely, Gramian Angular Fields (GAF) and Markov Transition Fields (MTF). This enables the use of techniques from computer vision for classification. Using a polar coordinate system, GAF images are represented as a Gramian matrix where each element is the trigonometric sum (i.e., superposition of directions) between different time intervals. MTF images represent the first order Markov transition probability along one dimension and temporal dependency along the other. We used Tiled Convolutional Neural Networks (tiled CNNs) on 12 standard datasets to learn high-level features from individual GAF, MTF, and GAF-MTF images that resulted from combining GAF and MTF representations into a single image. The classification results of our approach are competitive with five stateof-the-art approaches. An analysis of the features and weights learned via tiled CNNs explains why the approach works.
Catabolic repression of bacterial sporulation. (1965)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Peroxisome Proliferator-Activated Receptor-γ Coactivator 1α (PGC-1α): Transcriptional Coactivator and Metabolic Regulator (2003)

Investigations of biological programs that are controlled by gene transcription have mainly studied the regulation of transcription factors. However, there are examples in which the primary focus of biological regulation is at the level of a transcriptional coactivator. We have reviewed here the molecular mechanisms and biological programs controlled by the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha). Key cellular signals that control energy and nutrient homeostasis, such as cAMP and cytokine pathways, strongly activate PGC-1 alpha. Once PGC-1 alpha is activated, it powerfully induces and coordinates gene expression that stimulates mitochondrial oxidative metabolism in brown fat, fiber-type switching in skeletal muscle, and multiple aspects of the fasted response in liver. The regulation of these metabolic and cell fate decisions by PGC-1 alpha is achieved through specific interaction with a variety of transcription factors such as nuclear hormone receptors, nuclear respiratory factors, and muscle-specific transcription factors. PGC-1 alpha therefore constitutes one of the first and clearest examples in which biological programs are chiefly regulated by a transcriptional coactivator in response to environmental stimuli. Finally, PGC-1 alpha's control of energy homeostasis suggests that it could be a target for anti-obesity or diabetes drugs.
Laparoscopic Management of the Adnexal Mass (2006)

Ovarian neoplasms are common in women of all ages. As many as 10% of women in the United States will undergo surgical removal of an adnexal mass sometime in their lifetime. Gynecologic surgeons have pioneered laparoscopic surgery, developing what was originally a diagnostic tool into a safe and effective approach to management of adnexal masses. Accumulating scientific data support the laparoscopic approach to the adnexal mass as the preferred treatment.
Copper Converts the Cellular Prion Protein into a Protease-resistant Species That Is Distinct from the Scrapie Isoform (2001)

Several lines of evidence have suggested that copper ions play a role in the biology of both PrP(C) and PrP(Sc), the normal and pathologic forms of the prion protein. To further investigate this intriguing connection, we have analyzed how copper ions affect the biochemical properties of PrP(C) extracted from the brains of transgenic mice and from transfected cells. We report that the metal rapidly and reversibly induces PrP(C) to become protease-resistant and detergent-insoluble. Although these two properties are commonly associated with PrP(Sc), we demonstrate using a conformation-dependent immunoassay that copper-treated PrP is structurally distinct from PrP(Sc). The effect of copper requires the presence of at least one of the five octapeptide repeats normally present in the N-terminal half of the protein, consistent with the idea that the metal alters the biochemical properties of PrP by directly binding to this region. These results suggest potential roles for copper in prion diseases, as well as in the physiological function of PrP(C).
A negative selection scheme based on the expression of cytosine deaminase in plastids (1997)

The enzyme cytosine deaminase (CD) encoded by codA catalyzes deamination of cytosine to uracil. CD is present in prokaryotes and in many eukaryotic micro-organisms, but is absent in higher plants. 5-fluorocytosine (5FC) is metabolized in CD-expressing cells, causing cellular death. A chimeric codA has been introduced into the tobacco plastid genome and 5FC was used to select against tissue culture cells and seedlings expressing CD. This negative selection scheme will be useful in identifying nuclear genes which control plastid gene expression in higher plants.
OS11.5 ACT IV: An international, double-blind, phase 3 trial of rindopepimut in newly diagnosed, EGFRvIII-expressing glioblastoma (2017)

Background: The EGFR deletion mutation, EGFRvIII, is expressed in ~30% of glioblastomas (GBM). The EGFRvIII-targeted vaccine rindopepimut consists of EGFRvIII peptide conjugated to keyhole limpet hemocyanin (KLH). A survival benefit was observed in a randomized phase 2 trial of recurrent GBM (ReACT; n=73). In three phase 2 studies of 105 total patients with newly diagnosed, EGFRvIII+ GBM and minimal residual disease (MRD), the median overall survival (mOS) was 20–22 months, as compared to ~16 months for two matched contemporary datasets (n=16, n=29). Methods: Patients with newly diagnosed, resected, EGFRvIII+ GBM were, after standard chemoradiation, stratified by RPA class, MGMT promoter methylation, and geographic region, and randomized (1:1) to double-blind rindopepimut or control (KLH) concurrent with standard maintenance temozolomide. Primary endpoint is OS for MRD patients (enhancing tumor <2 cm2 post-chemoradiation by central review) aiming to detect hazard ratio (HR) ≤0.71 with 80% power and alpha=0.05 (log-rank test). Interim analyses were preplanned at 50% and 75% of events. Secondary analyses included patients with ≥2 cm2 of residual tumor (non-MRD). Results: 745 patients (405 MRD) were enrolled at 165 centers. The study was terminated for futility after the 2nd interim analysis (MRD OS HR=0.99). At final analysis, mOS for rindopepimut vs. control was 20.1 vs. 20.0 (HR=1.01; p=0.93) in the MRD cohort, and 14.8 vs. 14.1 (HR=0.79; p=0.066) with 2-year OS 30% vs. 19% in the non-MRD cohort. There were no substantial differences in progression-free survival. Rindopepimut was well tolerated (chief toxicity: injection site reaction) with robust anti-EGFRvIII immune response. Conclusions: The study failed to demonstrate a survival benefit for patients treated with rindopepimut and standard chemotherapy. Rindopepimut OS is comparable to prior studies, however, patients in the control arm fared better than historical controls. A trend for long-term survival benefit in non-MRD patients suggests a preferential effect in bulkier disease.
Nanoscale metal-semiconductor-metal photodetectors fabricated on SOI-substrates (2002)

Summary form only given. Interdigitated metal-semiconductor-metal (MSM) Schottky diode photodetectors based on silicon-on-insulator substrates (SOI) are attractive due to their high speed achievable at long wavelengths. In this work, MSM-PDs have been fabricated on SOI substrates using electron-beam lithography and lift-off techniques. DC and transient characterization of the SOI-MSM-PDs show low detector dark current, low depletion capacitance, high speed and reasonable photoresponse. Two different photodetectors were investigated: MSM1 with finger width and spacing of 200 nm, an active area of 9.5/spl times/18 /spl mu/m/sup 2/ and a top p-type Si-layer thickness of 0.5 /spl mu/m, and MSM2 with finger width and spacing of 70/400 nm, an active area of 9.5/spl times/29.5 /spl mu/m2 and a top n-type Si-layer thickness of 4 /spl mu/m. In order to achieve the Schottky contact, MSM1 was metallized with Ti-Au (20/30 nm), while MSM2 was metallized with Al (30 nm).
The N-Glycans Determine the Differential Blood Clearance and Hepatic Uptake of Human Immunoglobulin (Ig)a1 and Iga2 Isotypes (2000)

Human immunoglobulin (Ig)A exists in blood as two isotypes, IgA1 and IgA2, with IgA2 present as three allotypes: IgA2m(1), IgA2m(2), and IgA2m(n). We now demonstrate that recombinant, chimeric IgA1 and IgA2 differ in their pharmacokinetic properties. The major pathway for the clearance of all IgA2 allotypes is the liver. Liver-mediated uptake is through the asialoglycoprotein receptor (ASGR), since clearance can be blocked by injection of excess galactose-Ficoll ligand and suppressed in ASGR-deficient mice. In contrast, only a small percentage of IgA1 is cleared through this pathway. The clearance of IgA1 lacking the hinge region with its associated O-linked carbohydrate was more rapid than that of wild-type IgA1. IgA1 and IgA2 that are not rapidly eliminated by the ASGR are both removed through an undefined ASGR-independent pathway with half-lives of 14 and 10 h, respectively. The rapid clearance of IgA2 but not IgA1 through the liver may in part explain why the serum levels of IgA1 are greater than those of IgA2. In addition, dysfunction of the ASGR or altered N-linked glycosylation, but not O-glycans, that affects recognition by this receptor may account for the elevated serum IgA seen in liver disease and IgA nephropathy.
Anisotropy of NMR properties of tissues (1994)

Orientational anisotropy of T2 and T1 relaxation times, diffusion, and magnetization transfer has been investigated for six different tissues: tendon, cartilage, kidney, muscle, white matter, and optic nerve. Relaxation anisotropy was observed for tendon and cartilage, and diffusional anisotropy was measured in kidney, muscle, white matter, and optic nerve. All other NMR measurements of these tissues showed no orientational dependence. This pattern of NMR anisotropies can be interpreted from the underlying geometrical structures of the tissues.