gebhart/patrepeval huggingface dataset:
Ceramide 1‐Phosphate Phosphatase Activity in Brain (1993)

Recent studies have implicated sphingolipids in a variety of intracellular signaling systems. The finding that a calcium-stimulated ceramide kinase copurifies with neurotransmitter-containing vesicles suggests that ceramide, or one of its metabolites, has a role in neurotransmitter release. As a step toward understanding the role of ceramide kinase in vesicle functioning, this study sought to determine the metabolic fate of the product, ceramide 1-phosphate. We report that ceramide 1-phosphate is not deacylated by brain ceramidases to produce sphingosine 1-phosphate. It is, however, the substrate for a phosphatase activity that we name ceramide 1-phosphate phosphatase (CPPase). Subcellular fractionation studies suggest that CPPase is found in the synaptic terminal and is associated with both synaptic vesicle and plasma membranes. Divalent cations, most notably calcium, inhibit CPPase activity although not at concentrations that activate ceramide kinase. The existence of both ceramide kinase and CPPase activities at the synapse suggests that ceramide 1-phosphate production regulates some aspect of synaptic vesicle functioning.
Subsurface electrical impedance imagingusing orthogonal linear electrode arrays (1996)

The main limitation of electrical impedance tomography as an imaging modality is its inherently poor spatial resolution. Although more information about the impedance distribution within an object can be retrieved by the use of larger numbers of surface electrodes, the additional information tends to relate to regions of the object close to the electrodes rather than at depth. The paper describes the application of an image reconstruction approach originally developed for medical electrical impedance tomography to the alternative problem of mapping electrical impedance distributions in a subsurface volume. The use of this geometry allows the chosen imaged plane to be approximately uniformly sensed by a surface grid of electrodes leading to uniform resolution in the image and the possibility of exploiting the relatively high resolution information available at shallow depths. The advantage of the use of an electrode grid, treated as two orthogonal sets of parallel linear arrays, is demonstrated and the behaviour of the point-spread function in planes parallel to the surface plane examined. The application of a spatial frequency filter to counteract reconstruction blur is described. Simulated reconstructions of subsurface structures and an example biomedical image are presented.
P-selectin glycoprotein ligand 1 is a ligand for L-selectin on neutrophils, monocytes, and CD34+ hematopoietic progenitor cells. (1996)

Selectins play a critical role in initiating leukocyte binding to vascular endothelium. In addition, in vitro experiments have shown that neutrophils use L-selectin to roll on adherent neutrophils, suggesting that they express a nonvascular L-selectin ligand. Using a L-selectin/IgM heavy chain (mu) chimeric protein as an immunocytological probe, we show here that L-selectin can bind to neutrophils, monocytes, CD34+ hematopoietic progenitors, and HL-60 and KG-1 myeloid cells. The interaction between L-selectin and leukocytes was protease sensitive and calcium dependent, and abolished by cell treatment with neuraminidase, chlorate, or O-sialoglycoprotein endopeptidase. These results revealed common features between leukocyte L-selectin ligand and the mucin-like P-selectin glycoprotein ligand 1 (PSGL-1), which mediates neutrophil rolling on P- and E-selectin. The possibility that PSGL-1 could be a ligand for L-selectin was further supported by the ability of P-selectin/mu chimera to inhibit L-selectin/mu binding to leukocytes and by the complete inhibition of both selectin interactions with myeloid cells treated with mocarhagin, a cobra venom metalloproteinase that cleaves the amino terminus of PSGL-1 at Tyr-51. Finally, the abrogation of L- and P-selectin binding to myeloid cells treated with a polyclonal antibody, raised against a peptide corresponding to the amino acid residues 42-56 of PSGL-1, indicated that L- and P-selectin interact with a domain located at the amino-terminal end of PSGL-1. The ability of the anti-PSGL-1 mAb PL-1 to inhibit L- and P-selectin binding to KG-1 cells further supported that possibility. Thus, apart from being involved in neutrophil rolling on P- and E-selectin, PSGL-1 also plays a critical role in mediating neutrophil attachment to adherent neutrophils. Interaction between L-selectin and PSGL-1 may be of major importance for increasing leukocyte recruitment at inflammatory sites.
Inhibiting Breast Cancer Progression by Exploiting TGF&#946; Signaling (2010)

Transforming Growth Factor beta (TGFbeta) signaling influences most aspects of cellular function in addition to playing a major role in organ development, remodeling, and repair. Given the wide range of effects induced by TGFbeta, it is not surprising that alterations in TGFbeta signaling have been implicated in development and progression of many different cancer types. Within the context of breast cancer itself, TGFbeta is known to have a dual nature, being both tumor-suppressive during early breast cancer development and tumor-promoting during breast cancer metastasis. Targets for breast cancer therapeutics are greatly needed to decrease morbidity and mortality from this devastating disease. Here, we summarize what is known about TGFbeta in breast cancer progression and discuss potential TGFbeta targets for breast cancer therapeutics.
Catalytic contribution of flap-substrate hydrogen bonds in "HIV-1 protease" explored by chemical synthesis. (1993)

An analogue of "HIV-1 protease" was designed in which the ability to donate important water-mediated hydrogen bonds to substrate was precisely and directly deleted. Chemical ligation of unprotected peptide segments was used to synthesize this "backbone-engineered" enzyme. The functionally relevant amide -CONH- linkage between residues Gly49-Ile50 in each flap of the enzyme was replaced by an isosteric thioester -COS- bond. The backbone-engineered enzyme had normal substrate specificity and affinity (Km). However, the catalytic activity (kcat) was reduced approximately 3000-fold compared to the native amide bond-containing enzyme. Inhibition by the reduced peptide bond substrate analogue MVT-101 was unaffected compared with native enzyme. By contrast, the normally tight-binding hydroxyethylamine inhibitor JG-365 bound to the backbone-engineered enzyme with an approximately 2500-fold reduction in affinity. The reduced catalytic activity of the -Gly49-psi(COS)-Ile50-backbone-engineered enzyme analogue provides direct experimental evidence to support the suggestion that backbone hydrogen bonds from the enzyme flaps to the substrate are important for the catalytic function of the HIV-1 protease.
Differentiation-induced and constitutive transcription of human papillomavirus type 31b in cell lines containing viral episomes (1992)

The expression of viral genes during the productive life cycle of human papillomaviruses (HPV) is tightly coupled to the differentiation program of epithelial cells. We have examined transcription of HPV as a function of differentiation in an in vitro organotypic raft culture system which allows for epithelial stratification at the air-liquid interface. When CIN612 cells, which contain episomal copies of HPV type 31b (HPV31b), were allowed to stratify in raft cultures, they differentiated in a manner which was histologically similar to that seen in a cervical intraepithelial neoplasia I biopsy lesion. In monolayer cultures of CIN612 cells, two major polycistronic HPV31b transcripts of 1.7 kb which encode (i) E6, E7, E1-E4, and E5 and (ii) E6*, E7, E1-E4, and E5 were identified. These RNAs initiated at a promoter, P97, in the upstream regulatory region of the virus. Following differentiation in raft cultures, the relative abundance of RNAs initiated at P97 was unchanged. In contrast, the expression of a 1.3-kb RNA encoding an E1-E4 fusion protein and E5 was found to increase substantially following differentiation. This transcript was initiated at a novel promoter within the E7 gene (P742). These studies have therefore identified a constitutive viral promoter which is active throughout stratified epithelium as well as a novel promoter which is induced upon epithelial cell differentiation.
Low-loss 2- and 4-bit TTD MEMS phase shifters based on SP4T switches (2003)

2- and 4-bit microelectromechanical system (MEMS) X- to K/sub u/-band true-time-delay phase shifters with a very low insertion loss are described. The phase shifters are fabricated on 200-/spl mu/m GaAs substrates and the low loss is achieved using MEMS SP4T switches, which reduce the number of switches in the signal path by half when compared to conventional designs with SP2T switches. Measurements indicate an insertion loss of -0.6/spl plusmn/0.3 and -1.2/spl plusmn/0.5 dB at 10 GHz for the 2- and 4-bit designs, respectively. The measured losses agreed very well with Momentum simulations and are the lowest reported to date. The 2-bit phase shifter performed well from dc-18 GHz, with -0.8/spl plusmn/0.3-dB insertion loss at 18 GHz and a return loss of <-10.5 dB over dc-18 GHz.
Synthesis and characterization of biocompatible, degradable, light‐curable, polyurethane‐based elastic hydrogels (2007)

A series of degradable polyurethane-based light-curable elastic hydrogels were synthesized from polycaprolactone diol, polyethylene glycol (PEG), lysine diisocyanate (LDI), and 2-hydroxyethyl methacrylate (HEMA) through UV light initiated polymerization reaction. LDI was used as hard segment and polycaprolactone (PCL) and/or PEG were used as soft segments. By changing the PCL to PEG ratio during the prepolymer synthesis, polyurethanes with different soft segmental structures, hydrophilicity, and cytophilicity were obtained after light-initiated polymerization. The chemical structures of the synthesized polymers were characterized using differential scanning calorimetry and Fourier transform infrared spectroscopy. Physical properties such as swelling, mechanical properties, and in vitro degradation were evaluated. Materials containing a higher ratio of PEG exhibit higher water absorbance, higher degradation rate in vitro, and lower mechanical strength in the hydrated state. Mouse embryonal carcinoma-derived clonal chondrocytes were used as a model cell type to study the cytocompatibility of the synthesized polymers. Chondrocyte attachment, proliferation rates, and morphologies varied with changes in the PCL/PEG ratio. With a higher PEG ratio, lower cell attachment and proliferation were observed. To improve the cell attachment and proliferation on high PEG content hydrogels, bioactive molecules, such as peptides and proteins, were conjugated or immobilized in the gel matrix during the light-curing process. In this study, a short peptide, Arg-Gly-Asp-Ser, was used as a model biomolecule and incorporated into the gels during the light-curing process and improved cell growth was observed. In summary, the use of PCL/PEG at different ratios, as well as the introduction of HEMA into polyurethane, allows the synthesis of a series of biocompatible elastic hydrogels with tunable physical and cytophilic properties through light-initiated polymerization. This series of materials also allows for controlling cell attachment and growth by incorporating bioactive molecules during the light-curing process.
Real-Time Articulated Hand Pose Estimation Using Semi-supervised Transductive Regression Forests (2013)

This paper presents the first semi-supervised transductive algorithm for real-time articulated hand pose estimation. Noisy data and occlusions are the major challenges of articulated hand pose estimation. In addition, the discrepancies among realistic and synthetic pose data undermine the performances of existing approaches that use synthetic data extensively in training. We therefore propose the Semi-supervised Transductive Regression (STR) forest which learns the relationship between a small, sparsely labelled realistic dataset and a large synthetic dataset. We also design a novel data-driven, pseudo-kinematic technique to refine noisy or occluded joints. Our contributions include: (i) capturing the benefits of both realistic and synthetic data via transductive learning, (ii) showing accuracies can be improved by considering unlabelled data, and (iii) introducing a pseudo-kinematic technique to refine articulations efficiently. Experimental results show not only the promising performance of our method with respect to noise and occlusions, but also its superiority over state-of-the-arts in accuracy, robustness and speed.
Human skin fibroblast procollagenase: mechanisms of activation by organomercurials and trypsin (1983)

Pure human skin fibroblast procollagenase has been utilized in this study as a model system in which to examine the pathways of organomercurial and trypsin activation. Three organomercurials, p-(hydroxymercuri) benzoate, mersalyl, and p-aminophenylmercuric acetate, were able to fully activate human skin procollagenase with no accompanying loss of molecular weight. Lower molecular weight species were subsequently produced, particularly with a fourth organomercurial, phenylmercuric chloride. The activation process was dependent upon the concentration of the organomercurial compound and the time of incubation, but not on enzyme protein concentration. No evidence of a role for free sulfhydryls was found. Trypsin produced an initial cleavage product of procollagenase which was collagenolytically inactive yet underwent a concentration independent autocatalysis. Thus, procollagenase appeared to have an autocatalytic property which was enhanced by treatment with a variety of agents, all of which may function by perturbation of the zymogen conformation.
Osmium and Ruthenium Catalysts for Dehydrogenation of Alcohols (2011)

A series of pincer-type complexes of Os and Ru have been synthesized and investigated in catalytic alcohol dehydrogenation. The hydrides OsHCl(CO)[HN(C2H4PiPr2)2] and OsH2(CO)[HN(C2H4PiPr2)2] possess good air, moisture, and thermal stability and are outstanding versatile dehydrogenation catalysts for primary alcohols for reactions of transfer hydrogenation, dehydrogenative coupling, and amine alkylation.
Computational Fluid Dynamics Applied to Investigate Development and Optimization of Highly Conductive Channels within the Fracture Geometry (2016)

Abstract A conventional proppant pack may lose up to 99% of its conductivity due to gel damage, fines migration, multiphase flow, and non-Darcy flow. Therefore, pillar fracturing was developed to generate highly conductive paths for hydrocarbon to flow. This paper describes experimental results and numerical models of a new method of generating stable proppant pillars The proposed treatment method depends on fingering phenomena observed when a less viscous fluid, that does not carry proppant, is injected to displace a more viscous one that carries proppant. The low-viscosity fluid will channel through the high-viscosity fluid and create isolated proppant pillars. This method promises to reduce proppant costs, pumping horsepower, and gel damage compared to conventional treatments. Large-scale experiments (Slot tests: 2-ft height and 16-ft length) were performed to evaluate the development and stability of the created channels. In additional, a computational fluid dynamics (CFD) model was constructed using commercial CFD software, to simulate the experiment and to scale it up into full fracture dimensions. The study focused on effects of surface injection rate (1 to 120 bpm) and viscosity ratio (from 2 to 200) between the two injected fluids. Experimental results and numerical modeling confirmed that viscous fingering phenomena can be used to create a pillar fracture with conductive and stable channels. The numerical CFD model was able to accurately predict the experimental results. Increasing the injection rate reduces the main channel width while increasing the channel branching. Full piston displacement behavior was achieved after 60% of the fracture height, when a high-viscosity fluid displaced a low-viscosity fluid and their viscosity ratio was greater than 5. By reducing the viscosity ratio between the two fluids, the created channel shape converts from cylindrical (where the beginning and end of the channel have the same width) into conical behavior (where the beginning of the channel is wider than the end). This explains why the length of the channel decreases with the viscosity ratio between the two fluids. The distance between proppant pillars tends to be reduced with increasing distance from the wellbore, or with reduced pulse stage volume, time, or rate. A full description of the created channel (distance between proppant pillars) characteristics (size, width and length) will be presented in this paper.
Airway PI3K Pathway Activation Is an Early and Reversible Event in Lung Cancer Development (2010)

Although only a subset of smokers develop lung cancer, we cannot determine which smokers are at highest risk for cancer development, nor do we know the signaling pathways altered early in the process of tumorigenesis in these individuals. On the basis of the concept that cigarette smoke creates a molecular field of injury throughout the respiratory tract, this study explores oncogenic pathway deregulation in cytologically normal proximal airway epithelial cells of smokers at risk for lung cancer. We observed a significant increase in a genomic signature of phosphatidylinositol 3-kinase (PI3K) pathway activation in the cytologically normal bronchial airway of smokers with lung cancer and smokers with dysplastic lesions, suggesting that PI3K is activated in the proximal airway before tumorigenesis. Further, PI3K activity is decreased in the airway of high-risk smokers who had significant regression of dysplasia after treatment with the chemopreventive agent myo-inositol, and myo-inositol inhibits the PI3K pathway in vitro. These results suggest that deregulation of the PI3K pathway in the bronchial airway epithelium of smokers is an early, measurable, and reversible event in the development of lung cancer and that genomic profiling of these relatively accessible airway cells may enable personalized approaches to chemoprevention and therapy. Our work further suggests that additional lung cancer chemoprevention trials either targeting the PI3K pathway or measuring airway PI3K activation as an intermediate endpoint are warranted.
Mechanismen des biologischen Ionentransports – Carrier, Kanäle und Pumpen in künstlichen Lipidmembranen (1985)

Zellmembranen enthalten spezifische Systeme für den passiven und aktiven Ionentransport zwischen Cytoplasma und extrazellulärem Medium. Für eine Reihe von kleinen bis mittelgroßen Transportmolekülen wie Valinomycin und Gramicidin A liegen heute ausführliche strukturelle und kinetische Daten vor; in diesen Fällen ist es möglich, die Transportfunktion auf der Basis der Molekülstruktur zu verstehen. Durch Einbau in künstliche bimolekulare Lipidmembranen können die kinetischen Eigenschaften biologischer Transportsysteme im Detail untersucht werden.
The DNA Binding Activity and the Dimerization Ability of the Thyroid Transcription Factor I Are Redox Regulated (1995)

The DNA binding activity of the thyroid transcription factor-1 (TTF-1), a homeodomain-containing protein implicated in the control of thyroid- and lung-specific transcription, is controlled, in vitro, by the redox potential. Oxidation decreases TTF-1 DNA binding activity, which is fully restored upon exposure to reducing agents. The decrease in DNA binding activity is due to the formation of disulfide bond(s), formed between two specific cysteine residues located outside the TTF-1 homeodomain; hence, oxidation does not appear to directly hinder TTF-1/DNA contacts. Disulfide bond formation seems to stabilize preexisting, loosely associated, TTF-1 dimers, which, upon oxidation, proceed in the formation of specific, higher order oligomers.
Role of Cytokines in the Pathogenesis of Inflammatory Bowel Disease (2000)

Recent advances in the drug treatment of inflammatory bowel disease (IBD) have paralleled our understanding of the pathophysiology of ulcerative colitis and Crohn's disease. Several proinflammatory and immune-regulatory cytokines are upregulated in the mucosa of patients with IBD, and differences and similarities in the cytokine profiles of ulcerative colitis and Crohn's disease have been elucidated. Several clinical trials involving a chimeric anti-TNF-alpha (tumor necrosis factor-alpha) antibody have shown marked clinical benefit in the majority of patients with Crohn's disease, verifying the importance of TNF-alpha in the pathogenesis of Crohn's disease. In preliminary studies, treatment with recombinant human interleukin-10 has been beneficial in Crohn's disease but not in ulcerative colitis. Future treatment of IBD may include combination or sequential cytokine and anticytokine administration in defined groups of patients based on their mucosal cytokine profiles.
Dipeptide uptake: A novel marker for testicular and ovarian macrophages (1996)

These results indicate that the testicular and ovarian macrophages are equipped with a dipeptide transport system. The selective accumulation of the fluorescent dipeptide derivative beta-Ala-Lys-N epsilon-AMCA in testicular and ovarian macrophages permits the identification of these cell types under viable conditions.
Design considerations for tunneling MOSFETs based on staggered heterojunctions for ultra-low-power applications (2009)

This paper discusses key device design issues for ultra-low-power (0.3V) tunnel-injection nano-MOSFETs that incorporate staggered heterojunctions at the source-channel junction. Material choice, gate alignment, and doping strategy are found to be crucial to preserve essential performance features of a staggered-heterojunction TFET such as steep turn on, high on-state current drive and low off-state leakage.
Editing inducer elements increases A-to-I editing efficiency in the mammalian transcriptome (2017)

We propose a model where two regions of dsRNA are required for efficient editing: first, an RNA stem that recruits ADAR and increases the local concentration of the enzyme, then a shorter, less stable duplex that is ideal for efficient and specific catalysis. This discovery changes the way we define and determine a substrate for A-to-I editing. This will be important in the discovery of novel editing sites, as well as explaining cases of altered editing in relation to disease.
Alterations of pulsation absorber characteristics in experimental hydrocephalus (2010)

To the extent that the free CSF movement acts as a buffer of arterial pulsation input to flow in microvessels, alterations in the pulsation absorber may play a pathophysiological role. One measure of alterations in the way the brain deals with pulsatile input-the CPA measurement-changes dramatically with the imposition of hydrocephalus. Results in the present study suggest that CPA may serve as a complementary metric to the conventional static measure of intracranial compliance in other experimental and clinical studies.
Animal Models in Diabetes: A Primer (2000)

Animal Models of Diabetes: A Primer introduces characteristics of the most commonly used animal species with various diabetic syndromes which have been developed and extensively investigated during the last few decades. It includes Animal models that are readily available, well described and proven to be of value in the research of both types of diabetes. Extensively referenced, this book will be of value to new and established investigators, graduate students and pharmaceutical scientists working on the development of antidiabetic and preventative modalities in various areas of diabetes and its complications.Author: Shafrir, Eleazar Publisher: CRC Press Illustration: N Language: ENG Title: Animal Models in Diabetes: A Primer Pages: 00380 (Encrypted PDF) On Sale: 2000-12-21 SKU-13/ISBN: 9789058230966 Category: Health & Fitness : Diseases General