gebhart/patrepeval huggingface dataset:
Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells. I. Inhibition of de novo phosphatidylserine biosynthesis by exogenous phosphatidylserine and its efficient incorporation. (1986)

The effect of phosphatidylserine exogenously added to the medium on de novo biosynthesis of phosphatidylserine was investigated in cultured Chinese hamster ovary cells. When cells were cultured for several generations in medium supplemented with phosphatidylserine and 32Pi, the incorporation of 32Pi into cellular phosphatidylserine was remarkably inhibited, the degree of inhibition being dependent upon the concentration of added phosphatidylserine. 32Pi uptake into cellular phosphatidylethanolamine was also partly reduced by the addition of exogenous phosphatidylserine, consistent with the idea that phosphatidylethanolamine is biosynthesized via decarboxylation of phosphatidylserine. However, incorporation of 32Pi into phosphatidylcholine, sphingomyelin, and phosphatidylinositol was not significantly affected. In contrast, the addition of either phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, or phosphatidylinositol to the medium did not inhibit endogenous biosynthesis of the corresponding phospholipid. Radiochemical and chemical analyses of the cellular phospholipid composition revealed that phosphatidylserine in cells grown with 80 microM phosphatidylserine was almost entirely derived from the added phospholipid. Phosphatidylserine uptake was also directly determined by using [3H]serine-labeled phospholipid. Pulse and pulse-chase experiments with L-[U-14C] serine showed that when cells were cultured with 80 microM phosphatidylserine, the rate of synthesis of phosphatidylserine was reduced 3-5-fold whereas the turnover of newly synthesized phosphatidylserine was normal. Enzyme assaying of extracts prepared from cells grown with and without phosphatidylserine indicated that the inhibition of de novo phosphatidylserine biosynthesis by the added phosphatidylserine appeared not to be caused by a reduction in the level of the enzyme involved in the base-exchange reaction between phospholipids and serine. These results demonstrate that exogenous phosphatidylserine can be efficiently incorporated into Chinese hamster ovary cells and utilized for membrane biogenesis, endogenous phosphatidylserine biosynthesis thereby being suppressed.
Singlet Oxygen Release and Cell Toxicity of a Chemiluminescent Squaraine Rotaxane Dye: Implications for Molecular Imaging (2011)

The water soluble tetraguanidinium squaraine rotaxane 2 was prepared and photoconverted to its corresponding squaraine rotaxane endoperoxide (SREP), 2EP. As expected, 2EP undergoes a thermal cycloreversion reaction that releases 60 ± 4% singlet oxygen and produces near-infrared emission in aqueous solution. Cell toxicity assays in the dark, using human and bacterial cell cultures, showed that 2EP (up to 20 µM) is no more toxic than its parent 2. This suggests that SREP-derived imaging probes are not likely to exhibit a significant toxicity effect due to the slow release of stoichiometric amounts of singlet oxygen. Additional photosensitization experiments showed that tetraguanidinium squaraine rotaxane 2 is a weak photosensitizer, but nonetheless, red light irradiation of cell cultures that were pre-incubated with 2 (&amp;gt;3 µM) produced moderate phototoxicity. Fluorescence microscopy studies attribute the phototoxicity of 2 to its ability to penetrate into the cell cytosol. The implications of these results are discussed in the context of effective methods to activate SREP as chemiluminescent probes for in vivo optical molecular imaging.
Small, Nonpeptide p75NTRLigands Induce Survival Signaling and Inhibit proNGF-Induced Death (2006)

Studies showing that neurotrophin binding to p75NTR can promote cell survival in the absence of Trk (tropomyosin-related kinase) receptors, together with recent structural data indicating that NGF may bind to p75NTR in a monovalent manner, raise the possibility that small molecule p75NTR ligands that positively regulate survival might be found. A pharmacophore designed to capture selected structural and physical chemical features of a neurotrophin domain known to interact with p75NTR was applied to in silico screening of small molecule libraries. Small, nonpeptide, monomeric compounds were identified that interact with p75NTR. In cells showing trophic responses to neurotrophins, the compounds promoted survival signaling through p75NTR-dependent mechanisms. In cells susceptible to proneurotrophin-induced death, compounds did not induce apoptosis but inhibited proneurotrophin-mediated death. These studies identify a unique range of p75NTR behaviors that can result from isolated receptor liganding and establish several novel therapeutic leads.
DNA2 drives processing and restart of reversed replication forks in human cells (2015)

Accurate processing of stalled or damaged DNA replication forks is paramount to genomic integrity and recent work points to replication fork reversal and restart as a central mechanism to ensuring high-fidelity DNA replication. Here, we identify a novel DNA2- and WRN-dependent mechanism of reversed replication fork processing and restart after prolonged genotoxic stress. The human DNA2 nuclease and WRN ATPase activities functionally interact to degrade reversed replication forks with a 5'-to-3' polarity and promote replication restart, thus preventing aberrant processing of unresolved replication intermediates. Unexpectedly, EXO1, MRE11, and CtIP are not involved in the same mechanism of reversed fork processing, whereas human RECQ1 limits DNA2 activity by preventing extensive nascent strand degradation. RAD51 depletion antagonizes this mechanism, presumably by preventing reversed fork formation. These studies define a new mechanism for maintaining genome integrity tightly controlled by specific nucleolytic activities and central homologous recombination factors.
Bivalent disulfide-stabilized fragment variable immunotoxin directed against mesotheliomas and ovarian cancer. (2001)

We have used protein engineering to generate a stable bivalent fragment variable (Fv) molecule from the antimesothelin antibody SS, in which the VH and VL domains of the Fv are linked to each other by a disulfide bond, and the two Fvs are connected by a flexible 15-amino acid (Gly4-Ser)3 linker. The SS (dsFv)2 molecule is fused to a M(r) 38,000 truncated form of Pseudomonas exotoxin to generate a bivalent, disulfide stabilized, (dsFv)2 immunotoxin. The immunotoxin was expressed in Escherichia coli, refolded in vitro, and purified to approximately 95% purity with a high yield of > 10%. Binding studies demonstrated that the (dsFv)2 molecule has 40 times higher apparent affinity for recombinant mesothelin than a monovalent dsFv molecule. The (dsFv)2 immunotoxin was 4-10-fold more cytotoxic to three mesothelin antigen-positive cell lines than the monovalent dsFv immunotoxin. However, when tested in mice bearing tumor cells expressing mesothelin, the antitumor activity of the bivalent immunotoxin is very similar to the activity of the lower affinity monovalent immunotoxin. Our data indicate that increasing affinity of an antibody fragment does not necessarily lead to higher antitumor activity of an immunotoxin in vivo.
Correlation-preserved non-gaussian statistical timing analysis with quadratic timing model (2005)

Recent study shows that the existing first order canonical timing model is not sufficient to represent the dependency of the gate delay on the variation sources when processing and operational variations become more and more significant. Due to the nonlinearity of the mapping from variation sources to the gate/wire delay, the distribution of the delay is no longer Gaussian even if the variation sources are normally distributed. A novel quadratic timing model is proposed to capture the non-linearity of the dependency of gate/wire delays and arrival times on the variation sources. Systematic methodology is also developed to evaluate the correlation and distribution of the quadratic timing model. Based on these, a novel statistical timing analysis algorithm is propose which retains the complete correlation information during timing analysis and has the same computation complexity as the algorithm based on the canonical timing model. Tested on the ISCAS circuits, the proposed algorithm shows 10 /spl times/ accuracy improvement over the existing first order algorithm while no significant extra runtime is needed.
Expression of the zebrafish paired box gene pax[zf-b] during early neurogenesis (1991)

The paired box-containing (pax) gene family encodes a group of putative transcription factors differentially expressed during embryonic development. In this study, we describe the cloning and expression of a zebrafish gene pax[zf-b], which most probably is a direct homologue to the mouse Pax2 gene. The putative protein encoded by pax[zf-b] contains a paired box, an octapeptide, but no homeobox. However, a region of homology to the N-terminal half of paired-type homeoboxes is detected C-terminal to the pax[zf-b] paired domain. In zebrafish embryos, pax[zf-b] transcripts are first seen during the formation of the neural keel. At 9-10 h of development, two laterally located transverse stripes of cells expressing the gene appear in the rostral 1/3 of the embryo. The two areas subsequently move towards the midline and form the posterior portion of the midbrain. In the following stages of development, at 10-12 h, transcripts are detected in the otic placode, the Wolffian duct including the nephritic primodium and in the optic stalk. At a later time point, beginning at 14-15 h, single cells along the spinal cord, presumably interneurons, start to express the gene. The characteristic expression pattern of pax[zf-b] in the neural tube suggests an involvement of this gene in the regionalization of the midbrain as well as in the specification of neuronal cell fates at early embryonic stages.
Mechanisms for cytotoxic effects of anti–tumor necrosis factor agents on transmembrane tumor necrosis factor α–expressing cells: Comparison among infliximab, etanercept, and adalimumab (2008)

Abstract Objective Three anti–tumor necrosis factor α (anti‐TNFα) agents have been proved to be effective for rheumatoid arthritis (RA) and other inflammatory disorders. Infliximab and adalimumab have been generated as anti‐TNFα monoclonal antibodies, while etanercept is engineered from human type II TNF receptors. In spite of all 3 agents' equal efficacy for RA, both infliximab and adalimumab are effective for other diseases such as Crohn's disease and Wegener's granulomatosis, while etanercept is not. We undertook this study to understand the different clinical effects of these anti‐TNFα agents by analyzing their biologic activities on transmembrane TNFα. Methods Jurkat T cells stably expressing an uncleavable form of transmembrane TNFα were used for the following studies: 1) flow cytometric analysis of binding activities of anti‐TNF agents to cell surface transmembrane TNFα, 2) complement‐dependent cytotoxicity (CDC), 3) antibody‐dependent cell‐mediated cytotoxicity (ADCC) by using peripheral blood mononuclear cells, and 4) outside‐to‐inside (reverse) signal transduction through transmembrane TNFα estimated by apoptosis and cell cycle analysis using flow cytometry. Results All of the anti‐TNFα agents bound to transmembrane TNFα. Infliximab and adalimumab exerted almost equal CDC activities, while etanercept showed considerably lower activity. ADCC activities were almost equal among these 3 agents. Adalimumab and infliximab induced apoptosis and cell cycle arrest in transmembrane TNFα–expressing Jurkat T cells, reflecting an outside‐to‐inside signal transduction through transmembrane TNFα. Conclusion Three different anti‐TNF agents showed different biologic effects on transmembrane TNFα. This finding suggests that CDC and outside‐to‐inside signals by anti‐TNFα antibodies may explain the successful clinical efficacy of adalimumab and infliximab in Crohn's disease and Wegener's granulomatosis.
A New Class of HIV-1 Tat Antagonist Acting through Tat−TAR Inhibition (1998)

The main transcriptional regulator of the human immunodeficiency virus, the Tat protein, recognizes and binds to a small structured RNA element at the 5' end of every viral mRNA, termed TAR. On the basis of published structural data of the molecular interactions between TAR and Tat-related peptides, we defined requirements for potential low-molecular weight inhibitors of TAR recognition by the Tat protein. In accordance with the resulting concept, a series of compounds was synthesized. In vitro evaluation of their potential to directly interfere with Tat-TAR interaction was used to define a new chemical class of potent Tat antagonistic substances. The most active compound competed with Tat-TAR complexation with a competition dose CD50 of 22 nM in vitro and blocked HIV expression in a cellular Tat transactivation system with an IC50 of 1.2 microM. The close relation between structural features of the interaction between TAR and a new type of inhibitory agent, "In-PRiNts" (for inhibitor of protein-ribonucleotide sequences), such as CGP 40336A and those of the Tat-TAR complex was confirmed by RNase A footprinting and by two-dimensional NMR. Structural implications for the complex between this class of compounds and TAR RNA will be presented.
A virtual force approach for cooperative standoff target tracking using multiple robots (2016)

This paper presents a virtual force approach for cooperative standoff tracking of a stationary target using multiple robots. Each robot is governed by virtual forces, namely, virtual centripetal force, virtual spring forces and virtual drag forces. The virtual centripetal force counteracts the effect of the centrifugal force and ensures each robot orbit the target. The virtual springs make the orbiting radius converge to the desired standoff distance, and ensure the equidistant distribution of all the robots along the orbit. The virtual drag forces prevent oscillation during the convergence. The use of artificial physics makes the approach be based on solid theoretical foundation. Besides, the proposed approach is decentralized and the physical meanings of parameters are definite, which makes it easy to tune in application. The proof of the global stability and convergence are presented. Simulation results demonstrate the effectiveness of the virtual force approach.
Childhood Trauma and Adult Somatic Preoccupation by Body Area among Women in an Internal Medicine Setting: A Pilot Study (2001)

Among females in adulthood, all studied forms of abuse in childhood appear to contribute to general somatic preoccupation, as well as specific somatic symptoms in the chest and throat areas. Sexual abuse, specifically, is a unique predictor for general somatic preoccupation, but not necessarily specific body areas.
The bile acid synthetic gene 3β-hydroxy-Δ5-C27-steroid oxidoreductase is mutated in progressive intrahepatic cholestasis (2000)

We used expression cloning to isolate cDNAs encoding a microsomal 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase (C(27) 3beta-HSD) that is expressed predominantly in the liver. The predicted product shares 34% sequence identity with the C(19) and C(21) 3beta-HSD enzymes, which participate in steroid hormone metabolism. When transfected into cultured cells, the cloned C(27) 3beta-HSD cDNA encodes an enzyme that is active against four 7alpha-hydroxylated sterols, indicating that a single C(27) 3beta-HSD enzyme can participate in all known pathways of bile acid synthesis. The expressed enzyme did not metabolize several different C(19/21) steroids as substrates. The levels of hepatic C(27) 3beta-HSD mRNA in the mouse are not sexually dimorphic and do not change in response to dietary cholesterol or to changes in bile acid pool size. The corresponding human gene on chromosome 16p11.2-12 contains six exons and spans 3 kb of DNA, and we identified a 2-bp deletion in the C27 3beta-HSD gene of a patient with neonatal progressive intrahepatic cholestasis. This mutation eliminates the activity of the enzyme in transfected cells. These findings establish the central role of C(27) 3beta-HSD in the biosynthesis of bile acids and provide molecular tools for the diagnosis of a third type of neonatal progressive intrahepatic cholestasis associated with impaired bile acid synthesis.
Cangrelor: a review on its mechanism of action and clinical development (2009)

In patients with acute coronary syndromes and undergoing percutaneous coronary intervention, numerous large-scale clinical trials have shown that adjunctive treatment with the P2Y12 receptor antagonist clopidogrel in addition to aspirin reduces ischemic events. These studies underscore the importance of blockade of the P2Y12 signaling pathway in these settings. However, recent findings have shown that clopidogrel therapy may have some shortcomings. These include its broad range of interindividual-response profiles, where patients with low P2Y12 inhibitory effects have an increased risk of recurrent ischemic events, including stent thrombosis, and its irreversible mechanism of action. These observations underscore the need for novel antiplatelet agents overcoming these limitations. Cangrelor (AR-C69931MX) is an intravenous, direct-acting and reversible P2Y12 receptor antagonist. Cangrelor has a rapid onset and offset of action and achieves significantly greater degrees of platelet inhibition compared with clopidogrel. This article provides an overview of the current status of knowledge on cangrelor, focusing on its pharmacologic properties, clinical development and potential future applications.
Comparing Contact Angle Measurements and Surface Tension Assessments of Solid Surfaces (2010)

Four types of contact angles (receding, most stable, advancing, and "static") were measured by two independent laboratories for a large number of solid surfaces, spanning a large range of surface tensions. It is shown that the most stable contact angle, which is theoretically required for calculating the Young contact angle, is a practical, useful tool for wettability characterization of solid surfaces. In addition, it is shown that the experimentally measured most stable contact angle may not always be approximated by an average angle calculated from the advancing and receding contact angles. The "static" CA is shown in many cases to be very different from the most stable one. The measured contact angles were used for calculating the surface tensions of the solid samples by five methods. Meaningful differences exist among the surface tensions calculated using four previously known methods (Owens-Wendt, Wu, acid-base, and equation of state). A recently developed, Gibbsian-based correlation between interfacial tensions and individual surface tensions was used to calculate the surface tensions of the solid surfaces from the most stable contact angle of water. This calculation yielded in most cases higher values than calculated with the other four methods. On the basis of some low surface energy samples, the higher values appear to be justified.
Magnetic tunnel junctions with single-crystal electrodes: A crystal anisotropy of tunnel magneto-resistance (2000)

A strong dependence of tunnel magnetoresistance (TMR) on the crystal orientation of ferromagnetic electrodes was confirmed experimentally. We studied the TMR of Fe/Al2O3/Fe50Co50 tunnel junctions with single-crystal Fe electrodes of different crystal orientations and found that the TMR ratio increased from 13% to 42% at 2K (8% to 26% at room temperature) when the crystal orientation was changed from (100) to (211). Such a TMR anisotropy could be explained in terms of the anisotropic spin polarization of Fe bulk and/or interface electronic states. The importance of the "momentum-filtering" effect of the tunnel barrier was also discussed.
Dysfunctional High-Density Lipoprotein and the Potential of Apolipoprotein A-1 Mimetic Peptides to Normalize the Composition and Function of Lipoproteins (2011)

Although high-density lipoprotein-cholesterol (HDL-C) levels in large epidemiological studies are inversely related to the risk of coronary heart disease (CHD), increasing the level of circulating HDL-C does not necessarily decrease the risk of CHD events, CHD deaths, or mortality. HDL can act as an anti- or a pro-inflammatory molecule, depending on the context and environment. Based on a number of recent studies, it appears that the anti- or pro-inflammatory nature of HDL may be a more sensitive indicator of the presence or absence of atherosclerosis than HDL-C levels. The HDL proteome has been suggested to be a marker, and perhaps a mediator, of CHD. Apolipoprotein A-1 (apoA-I), the major protein in HDL is a selective target for oxidation by myeloperoxidase, which results in impaired HDL function. Improving HDL function through modification of its lipid and/or protein content maybe a therapeutic target for the treatment of CHD and many inflammatory disorders. HDL/apoA-I mimetic peptides may have the ability to modify the lipid and protein content of HDL and convert dysfunctional HDL to functional HDL. This review focuses on recent studies of dysfunctional HDL in animal models and human disease, and the potential of apoA-I mimetic peptides to normalize the composition and function of lipoproteins.
Characterizing the human hippocampus in aging and Alzheimer’s disease using a computational atlas derived from ex vivo MRI and histology (2018)

Although the hippocampus is one of the most studied structures in the human brain, limited quantitative data exist on its 3D organization, anatomical variability, and effects of disease on its subregions. Histological studies provide restricted reference information due to their 2D nature. In this paper, high-resolution (∼200 × 200 × 200 μm<sup>3</sup>) ex vivo MRI scans of 31 human hippocampal specimens are combined using a groupwise diffeomorphic registration approach into a 3D probabilistic atlas that captures average anatomy and anatomic variability of hippocampal subfields. Serial histological imaging in 9 of the 31 specimens was used to label hippocampal subfields in the atlas based on cytoarchitecture. Specimens were obtained from autopsies in patients with a clinical diagnosis of Alzheimer's disease (AD; 9 subjects, 13 hemispheres), of other dementia (nine subjects, nine hemispheres), and in subjects without dementia (seven subjects, nine hemispheres), and morphometric analysis was performed in atlas space to measure effects of age and AD on hippocampal subfields. Disproportional involvement of the cornu ammonis (CA) 1 subfield and stratum radiatum lacunosum moleculare was found in AD, with lesser involvement of the dentate gyrus and CA2/3 subfields. An association with age was found for the dentate gyrus and, to a lesser extent, for CA1. Three-dimensional patterns of variability and disease and aging effects discovered via the ex vivo hippocampus atlas provide information highly relevant to the active field of in vivo hippocampal subfield imaging.
Development and Validation of the Food‐Craving Inventory (2002)

The FCI was found to be a reliable and valid measure of general and specific food cravings. The FCI can be used in research related to overeating and binge eating. Also, it may be useful in treatment studies that target obesity and/or food cravings.
<title>Dense 3D surface acquisition by structured light using off-the-shelf components</title> (2000)

This paper describes the implementation of a LCD stripe projection system, based on a new processing scheme called line shift processing. One advantage of the method is, that the projection device cam, but is not required to be stable over time nor does it have to be calibrated. The new method therefore allows us to use an off-the-shelf multimedia projector to acquire dense 3D data of large objects in a matter of seconds. Since we are able to control our source of illumination, we can also acquire registered color information using standard monochrome cameras.