gebhart/patrepeval huggingface dataset:
Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor β (1994)

We have analysed the interactions of three proteoglycans of the decorin family, decorin, biglycan and fibromodulin, with transforming growth factor beta (TGF-beta). The proteoglycan core proteins, expressed from human cDNAs as fusion proteins with Escherichia coli maltose-binding protein, each bound TGF-beta 1. They showed only negligible binding to several other growth factors. Intact decorin, biglycan and fibromodulin isolated from bovine tissues competed with the fusion proteins for the TGF-beta binding. Affinity measurements suggest a two-site binding model with Kd values ranging from 1 to 20 nM for a high-affinity binding site and 50 to 200 nM for the lower-affinity binding site. The stoichiometry indicated that the high-affinity binding site was present in one of ten proteoglycan core molecules and that each molecule contained a low-affinity binding site. Tissue-derived biglycan and decorin were less effective competitors for TGF-beta binding than fibromodulin or the non-glycosylated fusion proteins; removal of the chondroitin/dermatan sulphate chains of decorin and biglycan (fibromodulin is a keratan sulphate proteoglycan) increased the activities of decorin and biglycan, suggesting that the glycosaminoglycan chains may hinder the interaction of the core proteins with TGF-beta. The fusion proteins competed for the binding of radiolabelled TGF-beta to Mv 1 Lu cells and endothelial cells. Affinity labelling showed that the binding of TGF-beta to betaglycan and the type-I receptors in Mv 1 Lu cells and to endoglin in endothelial cells was reduced, but the binding to the type-II receptors was unaffected. TGF-beta 2 and 3 also bound to all three fusion proteins. Latent recombinant TGF-beta 1 precursor bound slightly to fibromodulin and not at all to decorin and biglycan. The results show that the three decorin-type proteoglycans each bind TGF-beta isoforms and that slight differences exist in their binding properties. They may regulate TGF-beta activities by sequestering TGF-beta into extracellular matrix.
Gene3D: expanding the utility of domain assignments (2015)

Gene3D http://gene3d.biochem.ucl.ac.uk is a database of domain annotations of Ensembl and UniProtKB protein sequences. Domains are predicted using a library of profile HMMs representing 2737 CATH superfamilies. Gene3D has previously featured in the Database issue of NAR and here we report updates to the website and database. The current Gene3D (v14) release has expanded its domain assignments to ∼ 20,000 cellular genomes and over 43 million unique protein sequences, more than doubling the number of protein sequences since our last publication. Amongst other updates, we have improved our Functional Family annotation method. We have also improved the quality and coverage of our 3D homology modelling pipeline of predicted CATH domains. Additionally, the structural models have been expanded to include an extra model organism (Drosophila melanogaster). We also document a number of additional visualization tools in the Gene3D website.
Plasmid-Based RNA Interference: Construction of Small-Hairpin RNA Expression Vectors (2005)

Recent work demonstrates that RNA interference (RNAi) helps coordinate the flow of information from transcription to protein expression, complicating tremendously our former understanding of how protein expression is regulated (1,2). Inhibitory RNAs can be expressed naturally in cells as microRNAs (miRNAs) or introduced into cells as small, inhibitory RNAs (siRNAs). Both processes inhibit gene expression, but by different mechanisms. In general, miRNAs inhibit translation. One cellular process that benefits from “paused” translation is the nerve synapse (3). siRNAs inhibit expression through targeted degradation of target mRNA. Both miRNAs and siRNAs can be used at the bench to silence mRNA expression. In this chapter, we provide a practical approach to accomplish siRNA-mediated gene silencing, through the generation and introduction of plasmids expressing short-hairpin RNAs (shRNAs) that are subsequently processed to siRNAs in vivo.
The series elasticity of heart muscle during hypoxia (1971)

Using papillary muscle preparations from rat hearts, the compliance of the series elastic element was shown to be decreased during hypoxia. Series elastic compliance was decreased only under conditions resulting also in an alteration of resting length-force relations. It reverted to normal on reoxygenation.
Combinatorial Biosynthesis–An Approach in the Near Future? (1995)

A gene library has been conceived for the construction of multienzyme complexes from natural and altered building blocks. The first encouraging results have been achieved with polyketide synthases (PKSs): enzyme hybrids were formed by “mixing” genes coding for PKSs, which provide novel polyketides such as 1. The ring frameworks, configurations, and/or functional groups of these novel compounds depend on the manipulated genes.
Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation (1999)

Asthma is a clinical syndrome characterized by intermittent episodes of wheezing and coughing. The diagnosis is confirmed by abnormal lung physiology, including reversible airway obstruction and airways hyperresponsiveness (AHR). The pathologic manifestations of asthma include airway inflammation, airway remodeling, and mucus hypersecretion. Since the advent of bronchoscopy, we have been able to assess the lower airways in asthmatics during periods of disease activity and when the disease is quiescent and lung function is normal. From these studies, it has become clear that persistent inflammation is central to the pathogenesis of asthma. Bronchoscopic biopsies, bronchoalveolar lavage (BAL), and bronchoprovocation studies in patients with allergic asthma, intrinsic (nonallergic) asthma, or isocyanate-induced asthma show similar characteristic inflammatory responses. Increased numbers of inflammatory cells, predominantly eosinophils and lymphocytes, infiltrate the mucosa and submucosa in asthmatics independent of the etiology. It is now believed that airway inflammation leads to AHR (reviewed in ref. 1), airway remodeling (see article by Elias et al. in this series), and mucus hyperplasia (2, 3).
Validation of 2d iNverse Scattering Algorithms From Multi-Frequency Experimental Data (2000)

Reconstructions of two dimensional dielectric or conducting objects from multi-frequency experimental data are considered in the present paper. Two different iterative methods are used for solving the inverse scattering problem. The first one is based on a boundary integral formalism and retrieves boundaries and complex permittivities of unknown homogeneous scatterers. For this method initial guesses are derived from method of decomposition of the time reversal operator (DORT) combined with a low frequency approximation. The second method is based on a domain integral formalism and retrieves the relative complex permittivity distribution inside some investigated domain. The data were carried out in a controlled environment (anechoic chamber) and the reconstructions have been performed using multifrequency approach, i.e., the scheme starts with the lowest available frequency and uses the final result as initial guess at higher frequency in order to enhance the resolution.
Release of heparan sulfate from endothelial cells. Implications for pathogenesis of hyperacute rejection. (1990)

Heparan sulfate proteoglycan associated with endothelial cells in normal blood vessels inhibits intravascular coagulation and egress of blood cells and plasma proteins, key features of hyperacute rejection. It was shown herein that exposure of cultured porcine endothelium to human serum as a source of natural antibodies and complement caused cleavage and release of 5% of endothelial cell proteoglycans within 4 min and greater than 50% within 1 h. Proteoglycan release depended on activation of the classical complement pathway and preceded irreversible cell injury. These findings suggest that loss of endothelial cell proteoglycan may be a critical step in the pathogenesis of hyperacute rejection and in diseases involving humoral injury to endothelial cells.
PET imaging using radiolabelled antibodies: future direction in tumor diagnosis and correlate applications (2013)

Abstract: Immuno-positron emission tomography (PET) is a new imaging tool that finds application in diagnostic as well as in prognostic and therapeutic oncology. Monoclonal antibodies (mAbs) present the unique ability to selectively bind specific antigens produced by tumors, establishing the presence, location, and number of neoplastic foci. They are produced in unlimited quantities with absolute specificity using the hybridoma method. Treatment with mAbs can have different forms: they can be administered alone or can be combined with a radioactive molecule, which then delivers the radiation directly to the tumor cells. In immuno-PET, mAbs are labeled with various radionuclides and used in cancer patients who produce tumor-associated antigens. In this review we will discuss immuno-PET applications in tumor diseases, focusing on the technique, mAbs, positron emitter selection, and on its future applications. Keywords: Immuno-PET, monoclonal antibodies, radionuclides, radiolabeling
Transcript profiling of early lateral root initiation (2004)

At the onset of lateral root initiation in Arabidopsis thaliana, the phytohormone auxin activates xylem pole pericycle cells for asymmetric cell division. However, the molecular events leading from auxin to lateral root initiation are poorly understood, in part because the few responsive cells in the process are embedded in the root and are thus difficult to access. A lateral root induction system, in which most xylem pole pericycle cells were synchronously activated by auxin transport inhibition followed by auxin application, was used for microarray transcript profiling. Of 4,600 genes analyzed, 906 significantly differentially regulated genes were identified that could be grouped into six major clusters. Basically, three major patterns were discerned representing induced, repressed, and transiently expressed genes. Analysis of the coregulated genes, which were specific for each time point, provided new insight into the molecular regulation and signal transduction preceding lateral root initiation in Arabidopsis. The reproducible expression profiles during a time course allowed us to define four stages that precede the cell division in the pericycle. These early stages were characterized by G1 cell cycle block, auxin perception, and signal transduction, followed by progression over G1/S transition and G2/M transition. All these processes took place within 6 h after transfer from N-1-naphthylphthalamic acid to 1-naphthalene acetic acid. These results indicate that this lateral root induction system represents a unique synchronized system that allows the systematic study of the developmental program upstream of the cell cycle activation during lateral root initiation.
The Development of INT131 as a Selective PPARγ Modulator: Approach to a Safer Insulin Sensitizer (2008)

INT131 (formerly T0903131, T131, AMG131) is a potent non-thiazolidinedione (TZD) selective peroxisome proliferator-activated receptor gamma modulator (SPPARM) currently in Phase 2 clinical trials for treatment of type-2 diabetes mellitus (T2DM). This new chemical entity represents a second generation SPPARM approach developed after the first generation PPARgamma full agonists to address their inherent limitations. INT131 was specifically and carefully designed using preclinical models to exhibit a biological profile of strong efficacy with de minimis side effects compared to PPARgamma full agonists. As a potent PPARgamma modulator, INT131 binds to PPARgamma with high affinity. In pharmacology models of diabetes and in early clinical studies, it achieved a high level of efficacy in terms of antidiabetic actions such as insulin sensitization and glucose and insulin lowering, but had little activity in terms of other, undesired, effects associated with TZD PPARgamma full agonists such as edema and adipogenesis. Ongoing clinical development is directed at translating these findings into establishing a novel and effective treatment for T2DM patients with an improved safety profile in relation to that currently available.
Optimal multimodal fusion for multimedia data analysis (2004)

Considerable research has been devoted to utilizing multimodal features for better understanding multimedia data. However, two core research issues have not yet been adequately addressed. First, given a set of features extracted from multiple media sources (e.g., extracted from the visual, audio, and caption track of videos), how do we determine the best modalities? Second, once a set of modalities has been identified, how do we best fuse them to map to semantics? In this paper, we propose a two-step approach. The first step finds statistically independent modalities from raw features. In the second step, we use super-kernel fusion to determine the optimal combination of individual modalities. We carefully analyze the tradeoffs between three design factors that affect fusion performance: modality independence, curse of dimensionality, and fusion-model complexity. Through analytical and empirical studies, we demonstrate that our two-step approach, which achieves a careful balance of the three design factors, can improve class-prediction accuracy over traditional techniques.
Reconfigurable Square-Ring Microstrip Antenna (2013)

A reconfigurable design for a dual-feed square-ring microstrip patch antenna is described. The dual feeds are used to excite two orthogonal modes of the antenna, and each feed network is composed of a coupling patch, an impedance transformer, and a variable capacitor. In addition, the two feeds are connected to a single input port through a T-junction power divider. The proposed design can perform polarization diversity at different frequencies by tuning the capacitance values of the two capacitors. A prototype integrating with a pair of varactor diodes and related dc bias circuits is constructed. Typical experimental results are shown along with numerical simulation results. Both of them demonstrate that the prototype can provide one linear polarization and two circular polarizations at one operating frequency; moreover, the operating frequency can also be tuned to adjacent frequencies.
Cloned Cells Develop Renal Cortical Collecting Tubules (1994)

We investigated the development and morphogenesis of stem cells cloned from cultured transformed collecting duct cells of the rabbit in the presence of hepatocyte growth factor/scatter factor (HGF), vitamin A, laminin and transforming growth factors, HGF and vitamin A induced peanut agglutinin (PNA) positivity in nonprincipal cells (PC) but not in PCs, only HGF induced tubule formation. Although HGF induced a tubule-like arrangement in both cell lines, tubules with PNA-positive cells were observed only in non-PC cells incubated with HGF. Vasopressin increased intracellular free calcium in PNA-negative cells but not in PNA-positive cells. Intracellular pH increased in PNA-positive cells but not in PNA-negative cells when gluconate was substituted for Cl in the buffer. Cloned non-PCs were stem cells that developed PC- and IC-like characteristics and formed collecting ducts when incubated with HGF.
BCECF in Single Cultured Cells: Inhomogeneous Distribution but Homogeneous Response (1998)

Using confocal laser scanning microscopy with a dual-wavelength laser system, the behaviour of BCECF [(2',7'-bis-2-carboxyethyl)-5-(and-6)carboxyfluorescein] was investigated in a variety of cell lines. Selection of a small area for monitoring allowed discrimination between various intracellular organelles, whose identity was established by vital staining. It was found that, after loading the cells with BCECF, both the nucleus and the mitochondria showed a higher level of fluorescence than the cytoplasm. Calibration of the pH-sensitivity of these fluorescence signals using the nigericin method yielded identical curves, as did exposure of the cells to NH4Cl. These studies suggest that BCECF, despite its inhomogeneous intracellular distribution, reports the pH of only one cellular compartment, the cytosol.
The conversion of turraeanthin and turraeanthin A into simple meliacins by a route involving an oxidative rearrangement of probable biogenetic importance (1970)

Treatment of turraeanthin (VIII) and its 3α-epimer, turraeanthin A (IX), with sodium periodate in aqueous dioxan containing a trace of perchloric acid, followed by dehydration of the products with toluene-p-sulphonic acid in benzene, has afforded tetranortirucallane triterpenoids, (XIX), (XX), and (XXIII), containing a β-substituted furyl side-chain. Epoxidation of these tetranortriterpenoids followed by rearrangement by treatment with boron trifluoride–ether complex in benzene has provided a pathway to the simplest meliacins [e.g.(XXIX)].
nEmesis: Which Restaurants Should You Avoid Today? (2013)

Computational approaches to health monitoring and epidemiology continue to evolve rapidly. We present an end-to-end system, nEmesis, that automatically identifies restaurants posing public health risks. Leveraging a language model of Twitter users' online communication, nEmesis finds individuals who are likely suffering from a foodborne illness. People's visits to restaurants are modeled by matching GPS data embedded in the messages with restaurant addresses. As a result, we can assign each venue a "health score" based on the proportion of customers that fell ill shortly after visiting it. Statistical analysis reveals that our inferred health score correlates (r = 0.30) with the official inspection data from the Department of Health and Mental Hygiene (DOHMH). We investigate the joint associations of multiple factors mined from online data with the DOHMH violation scores and find that over 23% of variance can be explained by our factors. We demonstrate that readily accessible online data can be used to detect cases of foodborne illness in a timely manner. This approach offers an inexpensive way to enhance current methods to monitor food safety (e.g., adaptive inspections) and identify potentially problematic venues in near-real time.
ER Stress and UPR in Familial Amyotrophic Lateral Sclerosis (2006)

The primary mechanism by which mutations in Cu, Zn-superoxide dismutase (SOD1) contribute to progressive motor neuron loss in familial amyotrophic lateral sclerosis (FALS) remains unknown. Misfolded protein aggregates, ubiquitin-proteasome system impairment and neuronal apoptosis mediated by death receptor or mitochondrial-dependent pathways are implicated in mutant SOD1-induced toxicity. Recent evidence from cellular and transgenic rodent models of FALS proposes activation of a third apoptotic pathway linked to sustained endoplasmic reticulum (ER) stress. Here, we review the emerging role of ER stress and the unfolded protein response (UPR) in the pathogenesis of mutant SOD1-linked FALS. The UPR observed in FALS rodents is described which encompasses induction of key ER-resident chaperones during presymptomatic disease, leading to activation of stress transducers and pro-apoptotic molecules by late stage disease. Importantly, mutant SOD1 co-aggregates with UPR components and recruits to the ER, suggesting a direct adverse effect on ER function. By contrast, the opposing neuroprotective effects of wild-type SOD1 overexpression on UPR signalling are also highlighted. In addition, the potential impact of neuronal Golgi apparatus (GA) fragmentation and subsequent disturbances in intracellular protein trafficking on motor neuron survival in FALS is also discussed. We propose that ER stress and UPR may be coupled to GA dysfunction in mutant SOD1-mediated toxicity, promoting ER-initiated cell death signalling in FALS.
Effects of benzodiazepines and non‐benzodiazepine compounds on the GABA‐induced response in frog isolated sensory neurones (1989)

1. The effects of benzodiazepines and non-benzodiazepine compounds on the gamma-aminobutyric acid (GABA)-induced chloride current (ICl) were studied in frog isolated sensory neurones by use of a concentration-jump (termed 'concentration-clamp') technique, under single-electrode voltage-clamp conditions. The drugs used were classified into four categories as follows: full benzodiazepine receptor agonists (diazepam, clonazepam, nitrazepam, midazolam, clotiazepam and etizolam), partial agonists (CL 218,872, Ro 16-6028, Ro 17-1812 and Ro 23-0364), inverse agonists (Ro 15-3505, FG 7142 and beta-CCE) and a benzodiazepine receptor antagonist, Ro 15-1788 (flumazenil). 2. All full agonists at concentrations of 3 x 10(-6) M or less increased dose-dependently the peak amplitude of ICl elicited by 3 x 10(-6) M GABA to twice to three times larger than the control. However, no further augmentation of the GABA response was observed at concentrations of 1 x 10(-5) M or higher. Partial agonists also showed a dose-dependent augmentation of the GABA response at concentrations ranging from 3 x 10(-8) M to 3 x 10(-5) M, but their efficacies of augmentation of the GABA response were only about half or less of those of full agonists. Of the inverse agonists, beta-CCE had a unique dose-dependent effect on the GABA response. Beta-CCE reduced dose-dependently the GABA response at concentrations of less than 3 x 10(-6) M, but augmented it at concentrations of 3 x 10(-5) M and 6 x 10(-5) M. The inverse agonists reduced dose-dependently the GABA response. The benzodiazepine antagonist, flumazenil, slightly augmented the GABA response at concentrations between 3 x 10 7M and 3 x 10 5 M. 3. These results show clear differences in the effects on the GABA response between these four categories of compounds known to affect the benzodiazepine recognition site of the GABA/ benzodiazepine receptor-chloride channel complex. Our experimental system of frog isolated sensory neurones and a 'concentration-clamp' technique appears to be useful for evaluating efficacy of compounds on responses mediated by the GABA/benzodiazepine receptor-chloride channel complex.
Cloning of poly(3-hydroxybutyric acid) synthase genes ofRhodobacter sphaeroidesandRhodospirillum rubrumand heterologous expression inAlcaligenes eutrophus (1992)

From genomie libraries of the purple nonsulfur bacteria Rhodospirill,~m rubmm Ha and Rho,tobacter sphaeroides ATCC 17023 in tile broad-host range cosmid pVKI00, we cloned a 15-and a 14-kbp Hindlll restriction fragment, respectively.Each of these fragments restored the ability to accumulate poly(3-hydroxybutyrate) (PHB), in the PHB.negative mutant A/ca#genes eutrophus PHB-4.These hybrid cosmids also complemented PHB-negative mutants derived from wild-type R. mbmrn or R. sphaeroides.Both fragments hybridized with the PHB synthase structural gene of A. eutrophus HI6 and conferred the ability to express PHB synthase activity.Only the 15-kbp Hindlll fragment from R. rubrum conferred on the mutant PHB-4 the abil-
The Sensory Physiology of Host-Seeking Behavior in Mosquitoes (1991)

Presentation des aspects comportementaux de la recherche des hotes chez les moustiques. Evaluation des differents mecanismes d'attraction chez l'hote