gebhart/patrepeval huggingface dataset:
Antiangiogenic Therapies in Non-Small-Cell Lung Cancer (2018)

Angiogenesis is frequent in non-small-cell lung cancer (nsclc) and is associated with more aggressive disease. Many clinical trials have evaluated the addition of antiangiogenic therapy to standard therapies for patients with nsclc. Bevacizumab, a monoclonal antibody directed against serum vascular endothelial growth factor, in combination with carboplatin-paclitaxel chemotherapy, has been shown to improve survival for patients with nsclc. However, bevacizumab-based therapy is not suitable for many nsclc patients, including those with squamous histology, poor performance status, brain metastases, and the presence of bleeding or thrombotic disorders. Similar efficacy has also been seen with carboplatin-pemetrexed followed by maintenance pemetrexed chemotherapy. In the second-line setting, the addition of ramucirumab to docetaxel-or the addition of bevacizumab to paclitaxel-has resulted in a modest improvement in efficacy, although the clinical importance of those findings is questionable. Many trials in nsclc have also evaluated oral antiangiogenic compounds, both in the first line in combination with chemotherapy and upon disease progression either as combination or single-agent therapy. No clear improvements in overall survival have been observed, although a subgroup analysis of a trial evaluating the addition of nintedanib to docetaxel showed improved survival that was limited to patients with adenocarcinoma. Those findings require validation, however. All of the oral antiangiogenic agents result in added toxicities. Some agents have resulted in an increased risk of death, limiting their development. Available evidence supports a limited number of antiangiogenic therapies for patients with nsclc, but no biomarkers to help in patient selection are currently available, and additional translational research is needed to identify predictive biomarkers for antiangiogenic therapy.
Clonal assay of mouse mast cell colonies in methylcellulose culture (1982)

When mouse marrow and spleen cells were cultured for over 12 days in methylcellulose containing media conditioned by pokeweed-mitogen- stimulated spleen cells, colonies containing mast cells and blast cells were observed. The characteristic morphology of the colonies and the time course of their development allowed in situ identification of the mast cell colonies. Identification of the mast cells was confirmed by metachromatic staining with toluidine blue and alcian blue, transmission electron microscopy, and by demonstration of the membrane receptors for IgE. Coculture studies with male and female marrow cells strongly indicated the single cell origin of individual colonies. Detailed cytologic analyses of mixed hemopoietic colonies and replating experiments of individual mixed hemopoietic and mast cell colonies clearly established the hemopoietic origin of mast cells. In replating experiments of individual mast cell colonies, those without blast cells did not yield secondary mast cell colonies. This result strongly indicated that morphologically recognizable mast cells have lost their self-renewing capabilities. The quantitative nature of the mast cell colony assay was supported by linearity studies and provides a method for studies of the progenitors of mouse mast cells.
Cutting Edge: A Double-Mutant Knockin of the CD28 YMNM and PYAP Motifs Reveals a Critical Role for the YMNM Motif in Regulation of T Cell Proliferation and Bcl-xL Expression (2014)

CD28 is a critical regulator of T cell function, augmenting proliferation, cytokine secretion, and cell survival. Our previous work using knockin mice expressing point mutations in CD28 demonstrated that the distal proline motif was primarily responsible for much of CD28 function, whereas in marked contrast to prior studies, mutation of the PI3K-binding motif had little discernible effect. In this study, we examined the phenotype of mice in which both motifs are simultaneously mutated. We found that mutation of the PYAP motif unmasks a critical role for the proximal tyrosine motif in regulating T cell proliferation and expression of Bcl-xL but not cytokine secretion. In addition, we demonstrated that, although function is more severely impaired in the double mutant than in either single mutant, there remained residual CD28-dependent responses, definitively establishing that additional motifs can partially mediate CD28 function.
EEG source localization for two dipoles by neural networks (2002)

It is reported that neural networks are useful for solving physiological inverse problems such as EEG and MEG source localizations, where a single dipole source is localized in terms of position and direction. This method is developed here to localize two independent sources from EEG. To improve localization accuracy, 36 electrodes for EEG measurement are used and two dipole sources are assumed to be in each restricted region of the brain. As a result, localization accuracy has been about 3 to 9% depending on the region restrictions, which may be useful for real time epileptic diagnoses.
Mapping the In Vivo Distribution of Herpes Simplex Virions (1998)

We describe a method for labeling enveloped viral particles with a radiotracer, indium-111, allowing labeled viruses to be traced in vivo by nuclear imaging. After initial optimization experiments, a labeling efficiency of 83% (incorporation yield) was achieved for herpes simplex virus (HSV), resulting in a specific activity of 30 microCi/10(9) PFU. The labeling procedure did not significantly reduce the infectivity of the labeled virus and the virus did not release any significant amounts of the radionuclide within 12 hr after labeling. Sequential imaging of animals after intravenous administration of the labeled virus showed fast accumulation in the liver and redistribution from the blood pool (immediately after injection) to liver and spleen (12-24 hr after injection). At 12 hr after injection 7% of the virus-associated (111)In had been eliminated from the body and the remaining organ distribution of the virus was as follows: spleen 2.87 +/- 0.54% ID/g; liver, 2.60 +/- 0.51% ID/g; kidney, 0.98 +/- 0.31% ID/g; lung, 0.57 +/- 0.10% ID/g; [corrected] and lower amounts in other organs. Our results indicate that the described method allows qualitative and quantitative assessment of viral biodistribution in vivo by nuclear imaging.
ChemInform Abstract: AROMATIC TETRA‐AMIDINES: SYNTHESIS OF HALO‐DERIVATIVES AND THEIR ANTIPROTEOLYTIC ACTIVITY (1985)

Mono-halo derivatives of 1,3-di-(p-amidinophenoxy)-2,2-bis-(p-amidinophenoxymethyl)p ropane (TAPP-H) have been synthesized and their inhibitory effect on the bovine trypsin, bovine thrombin and porcine pancreatic kallikrein catalyzed hydrolysis of p-nitroanilides of amino acids was investigated, at pH 8.1 and 37 degrees, in parallel with that of TAPP-H and benzamidine. The addition of a halogen (Cl, Br or I) at position 2 of each benzamidine moiety of TAPP-H is accompanied by an increase of the inhibitory effect. This is especially evident in the case of porcine pancreatic kallikrein inhibition by TAPP-Cl. The structural basis of the different inhibitory effect of TAPP-H, TAPP-halo derivatives and benzamidine on the catalyzed hydrolysis of the proteinases examined are discussed and the role of Asp-189 in bovine trypsin, Asp-189 and Glu-149 or Asp-192 in bovine thrombin and Asp-189 and Asp-A148 or Glu-150 in porcine pancreatic kallikrein is focused.
Staphylococcus aureus α-Toxin: Nearly a Century of Intrigue (2013)

Staphylococcus aureus secretes a number of host-injurious toxins, among the most prominent of which is the small β-barrel pore-forming toxin α-hemolysin. Initially named based on its properties as a red blood cell lytic toxin, early studies suggested a far greater complexity of α-hemolysin action as nucleated cells also exhibited distinct responses to intoxication. The hemolysin, most aptly referred to as α-toxin based on its broad range of cellular specificity, has long been recognized as an important cause of injury in the context of both skin necrosis and lethal infection. The recent identification of ADAM10 as a cellular receptor for α-toxin has provided keen insight on the biology of toxin action during disease pathogenesis, demonstrating the molecular mechanisms by which the toxin causes tissue barrier disruption at host interfaces lined by epithelial or endothelial cells. This review highlights both the historical studies that laid the groundwork for nearly a century of research on α-toxin and key findings on the structural and functional biology of the toxin, in addition to discussing emerging observations that have significantly expanded our understanding of this toxin in S. aureus disease. The identification of ADAM10 as a proteinaceous receptor for the toxin not only provides a greater appreciation of truths uncovered by many historic studies, but now affords the opportunity to more extensively probe and understand the role of α-toxin in modulation of the complex interaction of S. aureus with its human host.
Diffusiophoresis of charged colloidal particles in the limit of very high salinity (2018)

Diffusiophoresis is the migration of a colloidal particle through a viscous fluid, caused by a gradient in concentration of some molecular solute; a long-range physical interaction between the particle and solute molecules is required. In the case of a charged particle and an ionic solute (e.g., table salt, NaCl), previous studies have predicted and experimentally verified the speed for very low salt concentrations at which the salt solution behaves ideally. The current study presents a study of diffusiophoresis at much higher salt concentrations (approaching the solubility limit). At such large salt concentrations, electrostatic interactions are almost completely screened, thus eliminating the long-range interaction required for diffusiophoresis; moreover, the high volume fraction occupied by ions makes the solution highly nonideal. Diffusiophoretic speeds were found to be measurable, albeit much smaller than for the same gradient at low salt concentrations.
Production, modification and bio-applications of magnetic nanoparticles gestated by magnetotactic bacteria (2009)

Magnetotactic bacteria (MTB) were first discovered by Richard P. Blakemore in 1975, and this led to the discovery of a wide collection of microorganisms with similar features i.e., the ability to internalize Fe and convert it into magnetic nanoparticles, in the form of either magnetite (Fe(3)O(4)) or greigite (Fe(3)S(4)). Studies showed that these particles are highly crystalline, monodisperse, bioengineerable and have high magnetism that is comparable to those made by advanced synthetic methods, making them candidate materials for a broad range of bio-applications. In this review article, the history of the discovery of MTB and subsequent efforts to elucidate the mechanisms behind the magnetosome formation are briefly covered. The focus is on how to utilize the knowledge gained from fundamental studies to fabricate functional MTB nanoparticles (MTB-NPs) that are capable of tackling real biomedical problems.
Functional Electrical Stimulation (2006)

The application of electricity for therapeutic purposes dates back to antiquity. However, the development of new technologies and innovative applications provide new and exciting potential for applications in rehabilitation. Electrical stimulation therapy involves the application of external electrical energy to tissue, which results in the stimulation of a physiological response. The degree and type of response depends on the mode, quantity, and quality of energy and the anatomical location of the application site.
Structural elucidation of trikoningins KA and KB, peptaibols from Trichoderma koningii (1993)

A Trichoderma koningii strain collected in Uruguay produced two antibiotic membrane-active peptidic groups, the trikoningins KA and KB, from which the main components KA V, KB I and KB II were purified. The peptide sequences were elucidated by FAB mass spectrometry and high-field NMR experiments. KA V was a nonadecapeptaibol, whereas KB I and KB II were two 11-residue lipopeptaibols. They all displayed antibiotic activity against Staphylococcus aureus. Their membrane-modifying properties were examined by following the leakage of liposome-entrapped carboxyfluorescein. KA V induced similar permeability modifications to those exhibited by known 19-residue peptaibols, while the KB I and KB II activities were weaker.
VEGFR‐3 in adult angiogenesis (2001)

Vascular endothelial growth factor receptor 3 (VEGFR-3, Flt-4), the receptor for vascular endothelial growth factors (VEGFs) C and D, is expressed on lymphatic endothelium and may play a role in lymphangiogenesis. In embryonic life, VEGFR-3 is essential for blood vessel development. The purpose of this study was to investigate whether VEGFR-3 is also involved in blood vessel angiogenesis in the adult. This was studied in human tissues showing angiogenesis and in a model of VEGF-A-induced iris neovascularization in the monkey eye, by the use of immunohistochemistry at the light and electron microscopic level. VEGFR-3 was expressed on endothelium of proliferating blood vessels in tumours. In granulation tissue, staining was observed in the proliferative superficial zone in plump blood vessel sprouts, in the intermediate zone in blood vessels and long lymphatic sprouts, and in the deeper fibrous zone in large lymphatics, in a pattern demonstrating that lymphangiogenesis follows behind blood vessel angiogenesis in granulation tissue formation. At the ultrastructural level, VEGFR-3 was localized in the cytoplasm and on the cell membrane of endothelial cells of sprouting blood vessels and sprouting lymphatics. In monkey eyes injected with VEGF-A, blood vessel sprouts on the anterior iris surface and pre-existing blood vessels in the iris expressed VEGFR-3. In conclusion, these results support a role for VEGFR-3 and its ligands VEGF-C and/or VEGF-D in cell-to-cell signalling in adult blood vessel angiogenesis. The expression of VEGFR-3 in VEGF-A-induced iris neovascularization and in pre-existing blood vessels exposed to VEGF-A suggests that this receptor and possibly its ligands are recruited in VEGF-A-driven angiogenesis.
New Molecular Targets for Cancer Chemotherapy (1994)

The Potential for Molecular Oncology to Define New Drug Targets (P. Workman). An Overview of the Regulation of Phospholipase-Linked Cell Signaling (M.J.O. Wakelam). Growth Factor Receptors as Targets (F.J. Lofts and W.J. Gullick). Protein Tyrosine Kinase Inhibitors (A. Levitzkie). Inhibitors of myo-Inositol Signaling (G. Powis and A. Kozikowski). The Properties of ras p21 and Its Potential Value as a Therapeutic Target (R.J.A. Grand). Protein Kinase C (A. Basu and J.S. Lazo). Apoptosis as a Target for Cancer Chemotherapy (A. Eastman and M.A. Barry). DNA Sequences as Targets for New Anticancer Agents (S. Neidle and D.E. Thurston). P-Glycoprotein, a Transporter with Allosterically Coupled Drug--Acceptor Sites as a Target for Rational Drug-Design (D.R. Ferry and D.J. Kerr). The Clinical Evaluation of Novel Chemotherapeutic Agents (C.J. Poole and D.J. Kerr). Index.
High-Frequency Sonophoresis: Permeation Pathways and Structural Basis for Enhanced Permeability (1994)

The mechanism of stratum corneum (SC) permeabilization by ultrasound (sonophoresis) is unknown. We studied here permeation pathways, and SC intercellular structural organization following applications of high-frequency sonophoresis to hairless mouse skin. Ruthenium tetroxide post-fixation and tracer solutions of LaNO3 and FITC-dextrans were employed to examine SC lamellar bilayers, lamellar body morphology and subcellular permeation pathways. Sonophoresis disrupted the compact organization of SC bilayers and LB-derived contents at the stratum granulosum (SG)-SC interface, leading to domain separation between 0 and 20 h, reverting by 48 h. Post-sonophoresis, tracers traversed the SC via lacunae within the lamellar bilayers, and via lamellae in sites that displayed domain separation. These studies provide insights about the penetration pathways, permeabilizing mechanisms, and kinetics of sonophoresis on the epidermis.
R-C3D: Region Convolutional 3D Network for Temporal Activity Detection (2017)

We address the problem of activity detection in continuous, untrimmed video streams. This is a difficult task that requires extracting meaningful spatio-temporal features to capture activities, accurately localizing the start and end times of each activity. We introduce a new model, Region Convolutional 3D Network (R-C3D), which encodes the video streams using a three-dimensional fully convolutional network, then generates candidate temporal regions containing activities, and finally classifies selected regions into specific activities. Computation is saved due to the sharing of convolutional features between the proposal and the classification pipelines. The entire model is trained end-to-end with jointly optimized localization and classification losses. R-C3D is faster than existing methods (569 frames per second on a single Titan X Maxwell GPU) and achieves state-of-the-art results on THUMOS'14. We further demonstrate that our model is a general activity detection framework that does not rely on assumptions about particular dataset properties by evaluating our approach on ActivityNet and Charades. Our code is available at http://ai.bu.edu/r-c3d/.
Direct comparison of binding equilibrium, thermodynamic, and rate constants determined by surface‐ and solution‐based biophysical methods (2002)

The binding interactions of small molecules with carbonic anhydrase II were used as model systems to compare the reaction constants determined from surface- and solution-based biophysical methods. Interaction data were collected for two arylsulfonamide compounds, 4-carboxybenzenesulfonamide (CBS) and 5-dimethyl-amino-1-naphthalene-sulfonamide (DNSA), binding to the enzyme using surface plasmon resonance, isothermal titration calorimetry, and stopped-flow fluorescence. We demonstrate that when the surface plasmon resonance biosensor experiments are performed with care, the equilibrium, thermodynamic, and kinetic constants determined from this surface-based technique match those acquired in solution. These results validate the use of biosensor technology to collect reliable data on small molecules binding to immobilized macromolecular targets. Binding kinetics were shown to provide more detailed information about complex formation than equilibrium constants alone. For example, although carbonic anhydrase II bound DNSA with twofold higher affinity than CBS, kinetic analysis revealed that CBS had a fourfold slower dissociation rate. Analysis of the binding and transition state thermodynamics also revealed significant differences in the enthalpy and entropy of complex formation. The lack of labeling requirements, high information content, and high throughput of surface plasmon resonance biosensors will make this technology an important tool for characterizing the interactions of small molecules with enzymes and receptors.
골재공장 주변에서 발생하는 비산먼지의 영향에 관한 연구 (2006)

골재공장에서 발생하는 비산먼지로 인한 피해가 증가하고 있다. 특히 직경 10㎛ 이하의 미세먼지(PM-10)의 경우 호흡기 및 심폐질환을 유발하는 등 인체에 직접적인 영향을 주는 것으로 알려졌다. 따라서 본 연구에서는 골재공장에서 배출된 먼지의 주변지역에 미치는 영향을 확산 모델링을 통해 예측 평가하였다.
Evaluation of Measurement Sites for Noninvasive Blood Glucose Sensing with Near-Infrared Transmission Spectroscopy (1999)

Six putative measurement sites were evaluated for noninvasive sensing of blood glucose by first-overtone near-infrared spectroscopy. The cheek, lower lip, upper lip, nasal septum, tongue, and webbing tissue between the thumb and forefinger were examined. These sites were evaluated on the basis of their chemical and physical properties as they pertain to the noninvasive measurement of glucose. Critical features included the effective optical pathlength of aqueous material within the tissue and the percentage of body fat within the optical path. Aqueous optical paths of 5 mm are required to measure clinically relevant concentrations of glucose in the first-overtone region. All of the tested sites met this requirement. The percentage of body fat affects the signal-to-noise ratio of the measurement and must be minimized for reliable glucose sensing. The webbing tissue contains a considerable amount of fat tissue and is clearly the worse measurement site. All other sites possess substantially less fat, with the least amount of fat in tongue tissue. For this reason, the tongue provides spectra with the highest signal-to-noise ratio and is, therefore, the site of choice on the basis of spectral quality.
MIME Encapsulation of Aggregate Documents, such as HTML (MHTML) (1999)

defines a powerful means of specifying multimedia documents.These multimedia documents consist of a text/html root resource (object) and other subsidiary resources (image, video clip, applet, etc. objects) referenced by Uniform Resource Identifiers (URIs) within the text/html root resource.When an HTML multimedia document is retrieved by a browser, each of these component resources is individually retrieved in real time from a location, and using a protocol, specified by each URI.In order to transfer a complete HTML multimedia document in a single e-mail message, it is necessary to: a) aggregate a text/html root resource and all of the subsidiary resources it references into a single composite message structure, and b) define a means by which URIs in the text/html root can reference subsidiary resources within that composite message structure.This document a) defines the use of a MIME multipart/related structure to aggregate a text/html root resource and the subsidiary resources it references, and b) specifies a MIME content-header (Content-Location) that allow URIs in a multipart/related text/html root body part to reference subsidiary resources in other body parts of the same multipart/related structure.Palme, et al.
Purple Deadnettle (Lamium purpureum) and Soybean Cyst Nematode Response to Cold Temperature Regimes (2007)

An experiment was conducted in growth chambers to determine the influence of cold temperature regimes, designed to simulate winter temperature conditions and spring recovery, on the interaction between purple deadnettle and soybean cyst nematode (SCN). The study was a factorial arrangement of treatments with five levels of temperature (20, 15, 10, 5, or 0 C), two levels of exposure time to the temperature (10 or 20 d), and two levels of recovery time at 20 C following exposure (0 or 20 d). In general, purple deadnettle shoot and root growth increased with temperature and time. The ability of purple deadnettle to recover from cold temperatures declined as the length of time that the plant was subjected to the cold temperature increased. SCN juveniles per gram of root at the conclusion of the temperature treatment declined as the temperature increased from 0 to 15 C, likely a result of continued purple deadnettle root growth and the inhibition of SCN hatch, growth, or development at those temperatures. SCN female, cyst, and egg production per gram of root generally increased with temperature and occurred under all temperature regimes. The results of this research indicate that, after hatching, SCN juveniles can survive a period of cold temperature inside the roots of a winter annual and continue development when transferred to warmer temperatures. Therefore, in a field environment, where fall or spring alone may not be sufficient for SCN to complete a reproductive cycle on a winter annual weed, the nematode may be able to reproduce by combining the fall and spring developmental periods.
Diagnosis of tetrahydrobiopterin (BH4) responsive mild phenylketonuria in Japan over the past 10 years. (2008)

A total of 31 patients was detected in the past 10 years, and the incidence detected using the provisional diagnostic criteria had increased to 25% among PAH deficient patients. BH4 treatment for BH4-responsive mild PKU is a new and effective pharmacotherapy, which replaces or liberalises the phenylalanine-restricted diets for a considerable number of mild PKU patients.