gebhart/patrepeval huggingface dataset:
SNX18 shares a redundant role with SNX9 and modulates endocytic trafficking at the plasma membrane (2010)

SNX18 and SNX9 are members of a subfamily of SNX (sorting nexin) proteins with the same domain structure. Although a recent report showed that SNX18 and SNX9 localize differently in cells and appear to function in different trafficking pathways, concrete evidence regarding whether they act together or separately in intracellular trafficking is still lacking. Here, we show that SNX18 has a similar role to SNX9 in endocytic trafficking at the plasma membrane, rather than having a distinct role. SNX18 and SNX9 are expressed together in most cell lines, but to a different extent. Like SNX9, SNX18 interacts with dynamin and stimulates the basal GTPase activity of dynamin. It also interacts with neuronal Wiskott-Aldrich syndrome protein (N-WASP) and synaptojanin, as does SNX9. SNX18 and SNX9 can form a heterodimer and colocalize in tubular membrane structures. Depletion of SNX18 by small hairpin RNA inhibited transferrin uptake. SNX18 successfully compensates for SNX9 deficiency during clathrin-mediated endocytosis and vice versa. Total internal reflection fluorescence microscopy in living cells shows that a transient burst of SNX18 recruitment to clathrin-coated pits coincides spatiotemporally with a burst of dynamin and SNX9. Taken together, our results suggest that SNX18 functions with SNX9 in multiple pathways of endocytosis at the plasma membrane and that they are functionally redundant.
Activation of 4-1BB on Liver Myeloid Cells Triggers Hepatitis via an Interleukin-27–Dependent Pathway (2018)

<b>Purpose:</b> Agonist antibodies targeting the T-cell costimulatory receptor 4-1BB (CD137) are among the most effective immunotherapeutic agents across preclinical cancer models. In the clinic, however, development of these agents has been hampered by dose-limiting liver toxicity. Lack of knowledge of the mechanisms underlying this toxicity has limited the potential to separate 4-1BB agonist-driven tumor immunity from hepatotoxicity.<b>Experimental Design:</b> The capacity of 4-1BB agonist antibodies to induce liver toxicity was investigated in immunocompetent mice, with or without coadministration of checkpoint blockade, via (i) measurement of serum transaminase levels, (ii) imaging of liver immune infiltrates, and (iii) qualitative and quantitative assessment of liver myeloid and T cells via flow cytometry. Knockout mice were used to clarify the contribution of specific cell subsets, cytokines, and chemokines.<b>Results:</b> We find that activation of 4-1BB on liver myeloid cells is essential to initiate hepatitis. Once activated, these cells produce interleukin-27 that is required for liver toxicity. CD8 T cells infiltrate the liver in response to this myeloid activation and mediate tissue damage, triggering transaminase elevation. FoxP3<sup>+</sup> regulatory T cells limit liver damage, and their removal dramatically exacerbates 4-1BB agonist-induced hepatitis. Coadministration of CTLA-4 blockade ameliorates transaminase elevation, whereas PD-1 blockade exacerbates it. Loss of the chemokine receptor CCR2 blocks 4-1BB agonist hepatitis without diminishing tumor-specific immunity against B16 melanoma.<b>Conclusions:</b> 4-1BB agonist antibodies trigger hepatitis via activation and expansion of interleukin-27-producing liver Kupffer cells and monocytes. Coadministration of CTLA-4 and/or CCR2 blockade may minimize hepatitis, but yield equal or greater antitumor immunity. <i>Clin Cancer Res; 24(5); 1138-51. ©2018 AACR</i>.
The Structure of OMCI, a Novel Lipocalin Inhibitor of the Complement System (2007)

The complement (C) system is a potent innate immune defence system against parasites. We have recently characterised and expressed OmCI, a 16 kDa protein derived from the soft tick Ornithodoros moubata that specifically binds C5, thereby preventing C activation. The structure of recombinant OmCI determined at 1.9 A resolution confirms a lipocalin fold and reveals that the protein binds a fatty acid derivative that we have identified by mass spectrometry as ricinoleic acid. We propose that OmCI could sequester one of the fatty acid-derived inflammatory modulators from the host plasma, thereby interfering with the host inflammatory response to the tick bite. Mapping of sequence differences between OmCI and other tick lipocalins with different functions, combined with biochemical investigations of OmCI activity, supports the hypothesis that OmCI acts by preventing interaction with the C5 convertase, rather than by blocking the C5a cleavage site.
The Potential Utility of 5-HT1A Receptor Antagonists in the Treatment of Cognitive Dysfunction Associated with Alzheimers Disease (2002)

The 5-HT1A receptor has been extensively studied over the last two decades. There is a plethora of information describing its anatomical, physiological and biochemical roles in the brain. In addition, the development of selective pharmacological tools coupled with our understanding of psychiatric pathology has lead to multiple hypotheses for the therapeutic utility of 5-HT1A agents and in particular 5-HT1A receptor antagonists. Over the last decade it has been suggested that 5-HT1A receptor antagonists may have therapeutic utility in such diseases as depression, anxiety, drug and nicotine withdrawal as well as schizophrenia. However, a very compelling rationale has been developed for the therapeutic potential of 5-HT1A receptor antagonists in Alzheimer s disease and potentially other diseases with associated cognitive dysfunction. Receptor blockade by a 5-HT1A receptor antagonist appears to enhance activation and signaling through heterosynaptic neuronal circuits known to be involved in cognitive processes and, as such, represents a novel therapeutic approach to the treatment of cognitive deficits associated with Alzheimer s disease and potentially other disorders with underlying cognitive dysfunction.
Inflammation 1: its role in the healing of acute wounds (2002)

The inflammatory response is an essential part of the wound-healing process. This article discusses inflammation in acute wounds and the part played by the migration of cells including neutrophils, macrophages and T-lymphocytes.
Functional analysis of grasping motion (2013)

This paper presents a novel grasping motion analysis technique based on functional principal component analysis (fPCA). The functional analysis of grasping motion provides an effective representation of grasping motion and emphasizes motion dynamic features that are omitted by classic PCA-based approaches. The proposed approach represents, processes, and compares grasping motion trajectories in a low-dimensional space. An experiment was conducted to record grasping motion trajectories of 15 different grasp types in Cutkosky grasp taxonomy. We implemented our method for the analysis of collected grasping motion in the PCA+fPCA space, which generated a new data-driven taxonomy of the grasp types, and naturally clustered grasping motion into 5 consistent groups across 5 different subjects. The robustness of the grouping was evaluated and confirmed using a tenfold cross validation approach.
Direct molecular level measurements of the electrostatic properties of a protein surface (1998)

In this work, we used direct measurements with the surface force apparatus to determine the pH-dependent electrostatic charge density of a single binding face of streptavidin. Mean field calculations have been used with considerable success to model electrostatic potential fields near protein surfaces, but these models and their inherent assumptions have not been tested directly at the molecular level. Using the force apparatus and immobilized, oriented monolayers of streptavidin, we measured a pI of 5-5.5 for the biotin-binding face of the protein. This differs from the pI of 6.3 for the soluble protein and confirms that we probed the local electrostatic features of the macromolecule. With finite difference solutions of the linearized Poisson-Boltzmann equation, we then calculated the pH-dependent charge densities adjacent to the same face of the protein. These calculated values agreed quantitatively with those obtained by direct force measurements. Although our study focuses on the pH-dependence of surface electrostatics, this direct approach to probing the electrostatic features of proteins is applicable to investigations of any perturbations that alter the charge distribution of the surfaces of immobilized molecules.
Differential effects of modern immunosuppressive agents on the development of intimal hyperplasia (2004)

Modern immunosuppressive agents such as tacrolimus and rapamycin are claimed to be associated with a reduction in vascular narrowing, a central feature of chronic rejection. This study assesses the effect of cyclosporine, tacrolimus and rapamycin on the development of intimal thickening, fibrosis-associated genes and deposition of extracellular matrix (ECM) proteins in a model of intimal hyperplasia. Male Sprague-Dawley rats received either no treatment or 5 mg/kg cyclosporine, 0.1 mg/kg tacrolimus or 0.05 mg/kg rapamycin. Animals underwent left common carotid balloon angioplasty, and intima medial ratios, pro-fibrotic gene expression and ECM accumulation were calculated at 14 and 28 days. Cyclosporine was associated with increased intimal thickening compared to controls ( P < 0.004). Tacrolimus had no effect on intimal thickening, whilst rapamycin significantly inhibited intimal thickening at both 14 and 28 days ( P < 0.004 and P < 0.026, respectively). All groups significantly inhibited matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, transforming growth factor (TGF)-beta and collagen III expression at 14 days ( P < 0.001), but increased ECM deposition. However, rapamycin marginally reduced ECM deposition compared to cyclosporine ( P < 0.06). Treatment with cyclosporine was associated with worsening of vascular narrowing, whilst rapamycin showed a beneficial reduction in intimal thickening. Treatment with all immunosuppressive agents resulted in increased ECM deposition. Rapamycin may halt the progression of vascular narrowing compared to both cyclosporine and tacrolimus.
Image-based display of activation patterns derived from scattered electrodes (1995)

Presentation of electrophysiologic data, such as activation patterns, can take many forms, the most common of which are hand- or machine-drawn isochronal maps. We present an image-based method which provides accurate matching between electrophysiologic data and the anatomic sites from which the data were derived. This method is linear, simple, and straightforward to implement, and presents results in a format which is easy to understand and interpret.
Substituierte Isatin‐phenylimine (1975)

Abstract 5‐Brom‐ und 5‐Nitro‐isatin kondensieren mit substituierten Anilinen zu Isatin‐3‐(phenyl)‐iminen. 5‐Brom‐isatin‐3‐(phenyl und naphthyl)‐imin werden auch durch Bromieren von Isatin‐3‐(phenyl und naphthyl)‐imin erhalten. Bei Einsatz von o‐Phenylendiamin erfolgt Ringschluß zu 5‐Brom‐bzw. 5‐Nitro‐6,11‐diaza‐5H‐benzo[b]carbazol, wobei als Zwischenprodukt wahrscheinlich die entsprechenden Isatin‐3‐(o‐amino‐phenyl)‐imine auftreten.
Signal transduction through lipid second messengers (1996)

This review emphasizes the generation of glycerolipid and sphingolipid second messengers, and their molecular targets. The role of the phosphatidylinositol transfer protein and phospholipase D in signal transmission, and the structures of the 1, 2-diacylglycerol and calcium-binding sites of protein kinase C are discussed. Further, ceramide signaling through protein kinases and the role of cross-talk in the signaling of apoptosis and inflammation are addressed.
Gamma Irradiation: Effects on Biomechanical Properties of Human Bone-Patellar Tendon-Bone Allografts (1995)

Sixty 10-mm bone-patellar tendon-bone allografts from young human donors were placed into four test groups, a control fresh-frozen group and three fresh-frozen ir radiated groups. The irradiated groups were exposed to 2.0, 3.0, or 4.0 Mrad of gamma irradiation. The speci mens were tested to tensile failure. The initial biome chanical strength of fresh-frozen allografts was reduced up to 15% when compared with fresh-frozen controls after 2.0 Mrad of irradiation. Maximum force, strain en ergy, modulus, and maximum stress demonstrated a statistically significant reduction after 2.0 Mrad of irra diation ( P&lt; 0.01). Stiffness, elongation, and strain were reduced but not with statistical significance. A 10% to 24% and 19% to 46% reduction in all biomechanical properties were found after 3.0 ( P &lt; 0.005) and 4.0 ( P &lt; 0.0005) Mrad of irradiation, respectively. After irra diation with a 4.0 Mrad dose, the ultimate load was be low that of reported values for the human anterior cru ciate ligament. It is clinically important to observe and document changes in human ligaments that result from currently used doses of gamma irradiation. The results from this study provide important information regarding the initial biomechanical properties of fresh-frozen hu man bone-patellar tendon-bone allografts after bacte rial sterilization with gamma irradiation. The current ac cepted dose for sterilization is between 1.5 and 2.5 Mrad. There appeared to be a dose-dependent effect of irradiation on all the biomechanical parameters studied. Four of seven parameters were found to be reduced after 2.0 Mrad of irradiation. Reductions were found in all parameters after 3.0 and 4.0 Mrad of irradiation.
Electronic effect on the elastic constant c44 of n-type silicon (1981)

The change of the elastic constant c44 of Si is theoretically investigated in the presence of both free electrons and bound electrons. While in p-type semiconductors the bound-hole contribution to the change of the elastic constant c44 is qualitatively different from the free-hole contribution, the bound-electron contribution in n-type Si is essentially identical to the free-electron contribution. It is shown that this phenomenon results from the facts that the donor ground state of silicon is a singlet and that the six conduction valleys of silicon are uniformly lowered by a shear acoustic wave.
Antioxidative activities of browning products of glucosamine fractionated by organic solvent and thin-layer chromatography. (1988)

遊離グルコサミンを粉末型,水溶型,無水型で加熱褐変させた試料,あるいはBGAをエタノール及びメタノールで分別した褐変物質,あるいは,TLC分画した画分の抗酸化性ならびにその性状について測定した結果は,次のとおりである. (1) もっとも強い抗酸化性を90℃, 1時間加熱褐変した粉末型のType Gで認めた.(2) エタノールあるいはメタノールによる分別では,不溶区でより強い抗酸化性を認めた.(3) TLCにより得た画分の抗酸化性は,分画前のものよりもすべて減少した.
The ISL phrase-based MT system for the 2007 ACL workshop on statistical machine translation (2007)

In this paper we describe the Interactive Systems Laboratories (ISL) phrase-based machine translation system used in the shared task "Machine Translation for European Languages" of the ACL 2007 Workshop on Statistical Machine Translation. We present results for a system combination of the ISL syntax-augmented MT system and the ISL phrase-based system by combining and rescoring the n-best lists of the two systems. We also investigate the combination of two of our phrase-based systems translating from different source languages, namely Spanish and German, into their common target language, English.
Development of a Fingertip Position-Sensing System using LC Resonated Markers (2007)

We propose a new system for sensing the positions of up to five wireless magnetic markers using phase detection. It consists of five resonated markers, a driving coil, and pickup coils. Slim LC resonated markers were fabricated and a detector was formed by connecting high-speed AD converters. The system has a position accuracy of around 1 mm, and can be used for highly accurate position sensing without magnetic shielding, because it is free from earth field noise. We tracked fingertips using five resonated markers.
Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction (2011)

URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT01156636.
Cationic Surfactants (1990)

Authors from Akzo, Sherex, and Ethyl chemical companies present a comprehensive review of cationic surfactants, emphasizing the organic chemistry aspects. They discuss the preparation, properties, availability, and commercial uses of a wide range of these materials, including aromatic and cyclic var
A completely synthetic toxoid vaccine containing Escherichia coli heat-stable toxin and antigenic determinants of the heat-labile toxin B subunit (1985)

The immunodeterminant regions of the Escherichia coli heat-labile toxin B subunit were identified by determining the antigenicity, by using enzyme-linked immunosorbent assays, of synthetically produced peptides corresponding to various segments of its 124-amino-acid sequence. The addition of the 18-amino-acid sequence of heat-stable toxin (ST) to some of these peptides enhanced their B subunit antigenicity. Peptide residues containing the 26 amino acids of B subunit sequence 58 to 83 joined to the 18-amino-acid sequence of ST yielded a 44-amino-acid peptide whose antigenicity was 50% that of both native B subunit and ST. This peptide was completely nontoxic when tested in Chinese hamster ovary tissue culture, suckling mouse, and rat ligated ileal loop assays. Peroral immunization of rats with the polymeric form of this peptide yielded a dose-dependent response of intestinal immunoglobulin A antitoxin titers to both the ST and B subunit components and provided strong protection against challenge with viable ST- and heat-labile toxin-producing E. coli strains. The immunogenicity of the synthetic peptide in rats was the same as that of ST and about 50% that of native B subunit. The completely synthetic peptide vaccine has the following advantages over previously described toxoid vaccines that consist of synthetic ST chemically cross-linked to native B subunit derived from bacterial cultures: it is produced by a single synthetic process, it is completely nontoxic, and it is immunogenic for both ST and B subunit.
Interleukin 3 (IL 3) regulates the in vitro proliferation of both blood monocytes and peritoneal exudate macrophages: synergism between a macrophage lineage-specific colony-stimulating factor (CSF-1) and IL 3. (1986)

The effect of interleukin 3 (IL 3) on regulation of macrophage proliferation was examined. Although IL 3 alone stimulates the colony formation in bone marrow cells, it fails to stimulate the colony formation by both peritoneal exudate macrophages (PEM) and blood monocytes. However, IL 3 greatly enhances the proliferative capacity of both PEM and monocytes in responding to suboptimal concentrations of CSF-1. At supraoptimal concentrations of CSF-1, IL 3 did not increase the number of colonies, but greatly increased colony size. Kinetic studies showed that IL 3 enhances CSF-1-induced macrophage proliferation by shortening the cell doubling time. Monocytes were more sensitive to the action of IL 3 and possessed higher proliferative potential than PEM. Binding studies with radioactive labeled CSF-1 (125I-CSF-1) showed that IL 3 treatment induced an increased expression of CSF-1 receptor activity by PEM which appears to be a result of increased number of available receptor sites. The effect of IL 3 on the expression of receptor activity is both dose- and time-dependent. IL 3 also augments the rate of receptor-mediated CSF-1 endocytosis by PEM which appears to be a direct result of increased expression of CSF-1 binding sites. These results demonstrate that, in addition to stimulating the growth and differentiation of several blood cell lineages by hemopoietic stem cells, IL 3 also possesses the ability to modulate CSF-1 receptors, thereby affecting proliferation of more mature blood monocytes and tissue-derived macrophages.
A Market-Oriented Programming Environment and its Application to Distributed Multicommodity Flow Problems (1993)

Market price systems constitute a well-understood class of mechanisms that under certain conditions provide effective decentralization of decision making with minimal communication overhead. In a market-oriented programming approach to distributed problem solving, we derive the activities and resource allocations for a set of computational agents by computing the competitive equilibrium of an artificial economy. WALRAS provides basic constructs for defining computational market structures, and protocols for deriving their corresponding price equilibria. In a particular realization of this approach for a form of multicommodity flow problem, we see that careful construction of the decision process according to economic principles can lead to efficient distributed resource allocation, and that the behavior of the system can be meaningfully analyzed in economic terms.
Effect of isoprostanes on bronchial smooth muscle in healthy and asthma-like horses (2000)

peer reviewed
Versatile Transmission Video Facilities at NBC New York (1976)

The operation of a television network requires the efficient and reliable processing of a great number of video signals not only from in-plant studios but also from diverse external sources via satellites, network land lines, and microwave systems. The new NBC Transmission Center provides direct monitoring access to 120 video inputs and 6 independent output channels (expandable to 10). It provides 26 video processing amplifiers and includes 30 source selectors for any of 100 inputs to 30 user entities; there is also a character generator “menu” display for supplying updated information on resource reassignment and emergency change. The use of patch cords has been greatly reduced compared to past practice.
Long-term follow-up of minimal residual disease in leukemia patients by monitoring WT1 (Wilms tumor gene) expression levels (1996)

Thirty-one patients (27 with acute myeloid leukemia [AML], 2 with acute lymphocytic leukemia [ALL], and 2 with acute mixed lineage leukemia [AMLL]) treated with conventional chemotherapy (CHT) and 23 patients (13 AML, 5 ALL, and 5 with chronic myeloid leukemia [CML]) treated with allogeneic bone marrow transplantation (BMT) were monitored for WT1 expression levels in BM and peripheral blood (PB) by reverse transcriptase-polymerase chain reaction over a long-term period (mean, 29 months for CHT and 24 months for BMT). Sixteen of the patients in the CHT group and 3 in the BMT group who had achieved complete remission suffered clinical relapse. In 10 of these patients, WT1 expression that had returned to normal BM levels (< 10(-3); the WT1 expression level of K562 cells was defined as 1.0) after complete remission (CR) either gradually or rapidly increased again to abnormal levels 1 to 18 months (mean, 7 months) before clinical relapse became apparent. In another 9 patients, WT1 expression never returned to normal BM levels even after CR and the subsequent relapse was accompanied by a rapid increase in WT1 expression to levels higher than 10(-2) (10(-3) levels in PB). On the other hand, the remaining 35 patients (15 CHT and 20 BMT) maintained their CR. In 29 of these patients (11 CHT and 18 BMT), WT1 expression either gradually or rapidly decreased to normal BM levels, whereas in the other 6 (4 CHT and 2 BMT), low or very low levels of WT1 mRNAs (10(-3) to 10(-2) in BM and 10(-5) to 10(-3) in PB) remain detectable, but without any clinical signs of relapse. A clear correlation was found to exist between the minimal residual disease (MRD) detected in the paired BM and PB samples for all types of leukemias (AML, ALL, and CML), with MRD in PB being approximately one-tenth of that in BM. WT1 quantitation of 168 paired BM and PB samples showed that PB samples were superior to BM samples for the detection of MRD. We conclude that monitoring of WT1 expression levels in BM and PB makes it possible to rapidly assess the effectiveness of individual treatment and diagnose clinical relapse in the early stage for all leukemia patients regardless of the presence or absence of tumor-specific DNA markers.