gebhart/patrepeval huggingface dataset:
Ligand‐induced activation of the insulin receptor: a multi‐step process involving structural changes in both the ligand and the receptor (2009)

Current models of insulin binding to the insulin receptor (IR) propose (i) that there are two binding sites on the surface of insulin which engage with two binding sites on the receptor and (ii) that ligand binding involves structural changes in both the ligand and the receptor. Many of the features of insulin binding to its receptor, namely B-chain helix interactions with the leucine-rich repeat domain and A-chain residue interactions with peptide loops from another part of the receptor, are also seen in models of relaxin and insulin-like peptide 3 binding to their receptors. We show that these principles can likely be extended to the group of mimetic peptides described by Schäffer and coworkers, which are reported to have no sequence identity with insulin. This review summarizes our current understanding of ligand-induced activation of the IR and highlights the key issues that remain to be addressed.
Gene expression and characterization of two 2‐oxoacid:ferredoxin oxidoreductases from Aeropyrum pernix K1 (2005)

A hyperthermophilic and aerobic crenarchaeon, Aeropyrum pernix K1, has two sets of genes possibly encoding 2-oxoacid:ferredoxin oxidoreductases. One is encoded in open reading frames (ORFs) ape2126 and ape2128, and the other in ORFs ape1473 and ape1472. The two sets of genes were expressed. The product enzymes, Ape2126/2128 and Ape1473/1472, showed optimal temperatures of 105 and over 110 degrees C, and optimal pHs of 8.5 and 9.0, respectively, using pyruvate as a substrate. Pyruvate, 2-oxobutyrate, and glyoxylate were the best substrates for both enzymes, and additionally Ape1473/1472 was able to act on 2-oxoglutarate, suggesting the enzyme operates in the TCA cycle.
Surface acoustic wave propagation in PZT/YBCO/SrTiO3and PbTiO3/YBCO/SrTiO3epitaxial heterostructures (1999)

Abstract Epitaxial heterostructures of ferroelectric thin films (PZT, PbTiO3) on SrTiO3 substrate offer highly c-axis oriented films with promising piezoelectric properties. Theoretical analysis of SAW propagation characteristics with IDT electrodes on top of the piezoelectric films has been performed to observe the effect of an underlying epitaxially matched conducting oxide layer of YBCO on SrTiO3 substrate. The change in SAW propagation characteristics with a SrTiO3 over-layer on PZT/SrTiO3 structure has also been studied. The SrTiO3 over-layer shows enhanced values of electromechanical coupling coefficient in the range of 3.65% to 12.72% for a SrTiO3 over-layer thickness varying from 0 to 0.12 λ.
Pharmacology of CFTR Chloride Channel Activity (1999)

Pharmacology of CFTR Chloride Channel Activity. Physiol. Rev. 79, Suppl.: S109-S144, 1999. - The pharmacology of cystic fibrosis transmembrane conductance regulator (CFTR) is at an early stage of development. Here we attempt to review the status of those compounds that modulate the Cl- channel activity of CFTR. Three classes of compounds, the sulfonylureas, the disulfonic stilbenes, and the arylaminobenzoates, have been shown to directly interact with CFTR to cause channel blockade. Kinetic analysis has revealed the sulfonylureas and arylaminobenzoates interact with the open state of CFTR to cause blockade. Suggestive evidence indicates the disulfonic stilbenes act by a similar mechanism but only from the intracellular side of CFTR. Site-directed mutagenesis studies indicate the involvement of specific amino acid residues in the proposed transmembrane segment 6 for disulfonic stilbene blockade and segments 6 and 12 for arylaminobenzoate blockade. Unfortunately, these compounds (sulfonylureas, disulfonic stilbenes, arylaminobenzoate) also act at a number of other cellular sites that can indirectly alter the activity of CFTR or the transepithelial secretion of Cl-. The nonspecificity of these compounds has complicated the interpretation of results from cellular-based experiments. Compounds that increase the activity of CFTR include the alkylxanthines, phosphodiesterase inhibitors, phosphatase inhibitors, isoflavones and flavones, benzimidazolones, and psoralens. Channel activation can arise from the stimulation of the cAMP signal transduction cascade, the inhibition of inactivating enzymes (phosphodiesterases, phosphatases), as well as the direct binding to CFTR. However, in contrast to the compounds that block CFTR, a detailed understanding of how the above compounds increase the activity of CFTR has not yet emerged.
Polyunsaturated Fatty Acids Are FXR Ligands and Differentially Regulate Expression of FXR Targets (2004)

Polyunsaturated fatty acids (PUFAs) have been previously reported as agonists of peroxisome proliferatoractivated receptor and antagonists of the liver X receptor. The activities on these two nuclear receptors have been attributed to their beneficial effects such as improvement of dyslipidemia and insulin sensitivity and decrease of hepatic lipogenesis. Here we report that PUFAs are ligands of farnesoid X receptor (FXR), a nuclear receptor for bile acids. In a conventional FXR binding assay, arachidonic acid (AA, 20:4), docosahexaenoic acid (DA, 22:6), and linolenic acid (LA, 18:3) had an affinity of 2.6, 1.5, and 3.5 microM, respectively. In a cell-free coactivator association assay, AA, DA, and LA decreased FXR agonist-induced FXR activation with IC(50)s ranging from 0.9 to 4.7 microM. In HepG2 cells, PUFAs regulated the expression of two FXR targets, BSEP and kininogen, in an opposite fashion, although both genes were transactivated by FXR. All three PUFAs dose-dependently enhanced FXR agonist-induced BSEP expression but decreased FXR agonist-induced human kininogen mRNA. Saturated fatty acids such as stearic acid (SA, 18:0) and palmitic acid (PA, 16:0) did not bind to FXR and did not change BSEP or kininogen expression. The pattern of BSEP and kininogen regulation by PUFAs is closely similar to that of the guggulsterone, previously reported as a selective bile acid receptor modulator. Our results suggest that PUFAs may belong to the same class of FXR ligands as guggulsterone, and that the selective regulation of FXR targets may contribute to the beneficial effects of PUFAs in lipid metabolism.
Elastic-model driven analysis of several views of a deformable cylindrical object (1996)

This paper proposes a method to extract regions of a deformable object from several views of it while finding the correspondence of the object among the views. The method has been developed to analyze X-ray images of a stomach. Owing to the physical (not physiological) deformation of the stomach and changes of the camera angle, the shape of the stomach regions are fairly different among the images. In order to collectively analyze these images, we use an elastic stomach model. Firstly, our method builds an elastic stomach model based on the stomach shape in one image. Considering each photographing condition, the deformation of the stomach in each image is simulated with the elastic model. Referring to the predicted contour which is obtained by projecting the deformed model from the camera angle of each image, the contour is robustly extracted from noisy images in a model-driven way. Since the predicted contour registered in each image corresponds with the elastic model, the position of each stomach part in the image is simultaneously obtained; corresponding parts can be found among the images through the model. Experimental results of analyzing several types of stomach X-ray images are shown and discussed.
Mutational Analysis of the Tyrosine Kinome in Colorectal Cancers (2003)

Tyrosine kinases (TKs) are central regulators of signaling pathways that control differentiation, transcription, cell cycle progression, apoptosis, motility, and invasion ( [1][1] ). Although a few TK genes have been shown to be mutationally altered in specific human cancers ( [1][1] ), it is not
Atrial Natriuretic Factor: A Hormone Produced by the Heart (1985)

Systematic studies on the significance of the secretory-like morphological characteristic of cardiac atrial muscle cells of mammals led to the finding that these cells produce a polypeptide hormone. This hormone, described in 1981 as atrial natriuretic factor (ANF), is diuretic (natriuretic), hypotensive, and has an inhibitory effect on renin and aldosterone secretion. Thus, ANF probably intervenes in the short- and long-term control of water and electrolyte balance and of blood pressure. Phylogenetically, ANF appears early, suggesting different functions for this peptide in accordance with each species' environment. Knowledge of the properties of the hormone should provide insights into the pathophysiology of important clinical entities and lead to the development of new pharmaceutical products.
T-bet, a T-Cell-Associated Transcription Factor, Is Expressed in a Subset of B-Cell Lymphoproliferative Disorders (2004)

T-bet, a T-box transcription factor, is expressed in CD4+ T lymphocytes committed to Th1 T-cell development and in a subset of T-cell non-Hodgkin lymphomas. Recent evidence indicates that T-bet also is expressed in B lymphocytes and might participate in immunoglobulin class switching. We examined T-bet expression in 116 cases of B-cell lymphoproliferative disorders by immunostaining and found that T-bet was expressed consistently in precursor B-cell lymphoblastic leukemia/lymphoblastic lymphoma (14/14 cases) in contrast with precursor T-cell lymphoblastic leukemia/lymphoblastic lymphoma, which is consistently T-bet– (13 cases), as previously reported. T-bet is expressed in memory B cell–derived neoplasms (chronic lymphocytic leukemia, marginal zone lymphoma, hairy cell leukemia; 35/42 cases) but not in cases of mantle cell, follicular, and large cell lymphoma (43 cases). Expression of T-bet in precursor B-cell lymphoblastic leukemia/lymphoblastic lymphoma was confirmed by Western blot analysis. The expression of T-bet in a significant subset of B-cell lymphoproliferative disorders but not in the vast majority of reactive B cells suggests it might have a role in the oncogenesis of T-bet+ B-cell neoplasms. In addition, T-bet should serve as a useful new marker for the diagnosis and subtyping of B-cell lymphoproliferative disorders.
Characterization of different promoters for designing a new expression vector in Saccharomyces cerevisiae (2010)

The widely used pESC vector series (Stratagene, La Jolla, CA, USA) with the bidirectional GAL1/GAL10 promoter provides the possibility of simultaneously expressing two different genes from a single vector in Saccharomyces cerevisiae. This system can be induced by galactose and is repressed by glucose. Since S. cerevisiae prefers glucose as a carbon source, and since its growth rate is higher in glucose than in galactose-containing media, we compared and evaluated seven different promoters expressed during growth on glucose (pTEF1, pADH1, pTPI1, pHXT7, pTDH3, pPGK1 and pPYK1) with two strong galactose-induced promoters (pGAL1 and pGAL10), using lacZ as a reporter gene and measuring LacZ activity in batch and continuous cultivation. TEF1 and PGK1 promoters showed the most constant activity pattern at different glucose concentrations. Based on these results, we designed and constructed two new expression vectors which contain the two constitutive promoters, TEF1 and PGK1, in opposite orientation to each other. These new vectors retain all the features from the pESC-URA plasmid except that gene expression is mediated by constitutive promoters.
Novel anchorage matrices for suspension culture of mammalian cells (1987)

Nonwoven fabrics were used as a support matrix for culturing anchorage-dependent diploid human lung fibroblast (IMR-90) cells. The most significant advantage of the fabrics is that low-inocula concentrations suffice to attain high final cell density. Cultures were successfully grown from inocula containing as little as 5% of the final number of cells, which is significantly lower than the 30–40% inocula concentrations typically required for tissue cell culture on dextran bead microcarriers, or on petri dishes or culture flasks. Nonwoven fabric cell supports also were superior to conventional spherical microcarriers for production of metabolic biopolymers (t-plasminogen activator) in serum-free media.
A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group (1991)

<h3>Objective.</h3> —To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis. <h3>Design.</h3> —Double-blind, randomized, placebo-controlled trial. <h3>Setting.</h3> —Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals. <h3>Patients.</h3> —Hospitalized adults with signs of gram-negative infection and a systemic septic response. <h3>Intervention.</h3> —Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later. <h3>Main Outcome Measures.</h3> —Mortality over the 30-day study period, resolution of organ failures, and safety. <h3>Results.</h3> —Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3;<i>P</i>=.01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (<i>P</i>=.05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified. <h3>Conclusions.</h3> —Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated. (<i>JAMA</i>. 1991;266:1097-1102)
Protecting privacy when disclosing information: k-anonymity and its enforcement through generalization and suppression (2018)

Today's globally networked society places great demand on the dissemination and sharing of person-specific data. Situations where aggregate statistical information was once the reporting norm now rely heavily on the transfer of microscopically detailed transaction and encounter information. This happens at a time when more and more historically public information is also electronically available. When these data are linked together, they provide an electronic shadow of a person or organization that is as identifying and personal as a fingerprint, even when the sources of the information contains no explicit identifiers, such as name and phone number. In order to protect the anonymity of individuals to whom released data refer, data holders often remove or encrypt explicit identifiers such as names, addresses and phone numbers. However, other distinctive data, which we term <em>quasi-identifiers</em>, often combine unquely and can be linked to publicly available information to re-identify individuals. In this paper we address the problem of releasing person-specific data while, at the same time, safeguarding the anonymity of individuals to whom the data refer. The approach is based on the definition of <em>k-anonymity</em>. A table provides <em>k-anonymity</em> if attempts to link explicitly identifying information to its contents ambiguiously map the information to at least k entities. We illustrate how k-anonymity can be provided by using generalization and suppression techniques. We introduce the concept of minimal generalization, which captures the property of the release process not to distort the data more than needed to achieve k-anonymity. We illustrate possible preference policies to choose among different minimal generalizations. Finally, we present an algorithm and experimental results when an implementation of the algorithm was used to produce releases of real medical information. We also report ont he quality of the released data by measuring precision and completeness of the results for different values of k.
A comparison of quality scheduling in commercial adaptive HTTP streaming solutions on a 3G network (2012)

There are many available commercial streaming solutions that perform quality adaption. An important issue with respect to users' perceived quality is how the system schedules the quality levels to match the available network resources. In this study, we compare several adaptive media players on the market to see how they perform in challenging streaming scenarios on a mobile 3G network. Bandwidth data collected in real-world field trials is used in all tests. We investigate how the media players respond to fluctuating bandwidth and outages, and how this affects the quality levels used, the bandwidth utilization, and the number and duration of buffer underruns. We found significant differences in performance and optimization goals between the different players' schedulers. We conclude that the quality scheduler is an important factor in providing a satisfying quality of experience when using an adaptive media player.
Recent Developments in Protein and Cell-Targeted Aptamer Selection and Applications (2011)

Because of their easily modified chemical structures and wide range of targets, aptamers are ideal candidates for various applications, such as biomarker discovery, target diagnosis, molecular imaging, and drug delivery. Aptamers are oligonucleotide sequences that can bind to their targets specifically via unique three dimensional (3-D) structures. Usually, aptamers are obtained from repeated rounds of in vitro or in vivo selection termed SELEX (Systematic Evolution of Ligands by EXponential enrichment), which can generate aptamers with high affinity and specificity for many kinds of targets, such as biomedically important proteins and even cancer cells. In this review, some basic principles and recent developments in the design of SELEX process are discussed, hopefully to provide some guidelines towards performing more efficient aptamer isolation procedures. Moreover, the biomedical and bioanalytical applications of aptamers are further reviewed, based on some smart biochemical modifications of these oligonucleotide structures.
Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation. (1977)

A study was carried out on mechanisms, independent of activated Factor XI, capable of activating Factor IX. The reaction product of tissue factor and Factor VII functioned as a potent Factor IX activator in the assay system used. Activated Factor IX itself activated Factor X; thrombin failed to activate Factor IX. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis confirmed that the reaction product of tissue factor and Factor VII activated Factor IX, with replacement of the band corresponding to native factor IX [molecular weight (Mr) 55,000] by bands corresponding to the heavy chain (Mr 27,000) and light chain (Mr 17,000) of activated Factor IX. When either Factor VII or calcium ions were left out of incubation mixtures, the band of native Factor IX persisted unchanged. Contact of blood with tissue factor represents a second mechanism, bypassing activated Factor XI, for the activation of Factor IX during hemostasis. It may help to explain the discrepancy between the mild bleeding of hereditary Factor XI deficiency and the severe bleeding of hereditary Factor IX deficiency.
Analgetic and antiinflammatory 7-aroylbenzofuran-5-ylacetic acids and 7-aroylbenzothiophene-5-ylacetic acids (1986)

A number of 7-benzoylbenzofuran-5-ylacetic acids and 7-benzoylbenzothiophene-5-ylacetic acids were synthesized. The compounds were generally only 1/2 to 3 times as potent as phenylbutazone in the rat paw edema antiinflammatory assay. However, they show greater activity as analgetic agents. The most active compound is 7-[4-(methylthio)-benzoyl]benzofuran-5-ylacetic acid (5g) having 57 times the potency of aspirin in the mouse writhing analgetic assay. This compound caused virtually no gastric ulceration in rats at doses of up to 90 mg/kg.
α-DNA IV: α-anomeric and β-anomeric tetrathymidylates covalently linked to intercalating oxazolopyridocarbazole. Synthesis, physicochemical properties and poly (rA) binding (1987)

A new set of molecules made of an intercalating agent (oxazolopyridocarbazole, OPC) covalently linked through a polymethylene chain of various length to the 3' end of alpha-anomeric or beta-anomeric tetradeoxynucleotides (alpha- or beta-T4) have been synthesized. The beta-thymidylate modified compound (beta-T4C5OPC) is able to interact with the complementary sequence, beta-poly (rA); this interaction is strongly stabilized compared to the parent compound, beta-oligo(dT)4 and is specific for poly (rA). The molecule synthesized from the unnatural alpha-anomer, alpha-T4C5OPC, is also able to interact with poly (rA) leading to the formation of an alpha-beta hybrid stabilized by the energy provided by the OPC moiety. The stoechiometry of the binding reaction shows that an A-T pairing occurs in the alpha-beta heterohybrids. Tm studies reveal that the alpha-beta heterohybrids are more stable than their beta-beta counterparts.
Neurosurgeons' perspectives on psychosurgery and neuroenhancement: a qualitative study at one center (2010)

There is support in the neurosurgical community for the surgical management of refractory psychiatric disease. The use of neuromodulation for the alteration of nonpathological traits is morally and ethically dubious when it is out of sync with the values of society at large. Both DBS and neuromodulation will have far-reaching and profound public health implications.
Octilinear Steiner tree construction (2003)

There is a renewed interest on 45/spl deg/ geometry (4-geometry) after Simplex introduced X Architecture for its diagonal routing. Given a rectilinear Steiner tree T/sub 2/ = (V, E), we propose a O(|V| + |E|) algorithm to build an isomorphic octilinear Steiner tree T/sub 4/. Moreover, /spl omega/(T/sub 2/) - (/spl Rfr//sub e/ + /spl Rfr//sub /spl nu//) /spl omega/(T/sub 4/), where /spl omega/(T/sub 2/) and /spl omega/(T/sub 4/) are the total wirelength of T/sub 2/ and T/sub 4/, respectively. The /spl Rfr//sub e/ is the wirelength reduction from edge conversion and R, is the wirelength reduction by sliding degree three Steiner point. The /spl Rfr//sub e/ = /spl Sigma/i=1/sup |E|/ (2 - /spl radic/2) /spl times/ Min(/spl Delta/x/sub i/, /spl Delta/y/sub i/), where, /spl Delta/x/sub i/ and /spl Delta/y/sub i/ are horizontal and vertical wirelength for edge e/sub i/, e/sub i/ /spl isin/ E. The /spl Rfr//sub /spl nu// is the sum of wirelength reduction from sliding all degree three Steiner points. For each degree three Steiner point /spl nu/, /spl nu/ /spl isin/ V, the sliding reduces (3 - 2/spl radic/2) /spl times/ M in(/spl Delta//spl omega//sub 1/, /spl Delta//spl omega//sub 2/, /spl Delta//spl omega//sub 3/), where /spl Delta//spl omega//sub 1/, /spl Delta//spl omega//sub 2/ and /spl Delta//spl omega//sub 3/ are the wirelength of three wire segments connect to /spl nu/. Moreover, we prove the /spl omega/(T/sub 4/) obtained from our algorithm is the lower bound for T/sub 2/'s isomorphic 4-geometry Steiner tree. In the end, we show average 6.63% wirelength reduction on 15 designs by using our algorithm.