gebhart/patrepeval huggingface dataset:
Protein engineering (1986)

Journal Article Protein engineering Get access Robin J. Leatherbarrow, Robin J. Leatherbarrow Department of Chemistry Impenal College of Science & TechnologySouth Kensington, London SW7 2AY. UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Alan R. Fersht Alan R. Fersht Department of Chemistry Impenal College of Science & TechnologySouth Kensington, London SW7 2AY. UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Protein Engineering, Design and Selection, Volume 1, Issue 1, October 1986, Pages 7–16, https://doi.org/10.1093/protein/1.1.7 Published: 01 October 1986 Article history Received: 17 July 1986 Published: 01 October 1986
HONING DEFENCE'S INTELLECTUAL EDGE (2011)

Abstract The new generation of servicemen and women are better informed, more opinionated and more comfortable in the modern information environment. Ensuring that they are equipped with the conceptual component of their professional toolkit, as well as the physical and moral, is a vital challenge, particularly as it requires looking to the future's rather than the past's way of doing business.
Regulation of translation factors during hindlimb unloading and denervation of skeletal muscle in rats (2001)

In the rat, denervation and hindlimb unloading are two commonly employed models used to study skeletal muscle atrophy. In these models, muscle atrophy is generally produced by a decrease in protein synthesis and an increase in protein degradation. The decrease in protein synthesis has been suggested to occur by an inhibition at the level of protein translation. To better characterize the regulation of protein translation, we investigated the changes that occur in various translation initiation and elongation factors. We demonstrated that both hindlimb unloading and denervation produce alterations in the phosphorylation and/or total amount of the 70-kDa ribosomal S6 kinase, eukaryotic initiation factor 2 alpha-subunit, and eukaryotic elongation factor 2. Our findings indicate that the regulation of these protein translation factors differs between the models of atrophy studied and between the muscles evaluated (e.g., soleus vs. extensor digitorum longus).
The monocyte Fcγ receptors FcγRI/γ and FcγRIIA differ in their interaction with Syk and with Src-related tyrosine kinases (2004)

There are important differences in signaling between the Fc receptor for immunoglobulin G (IgG) FcgammaRIIA, which uses the Ig tyrosine-activating motif (ITAM) within its own cytoplasmic domain, and FcgammaRI, which transmits signals by means of an ITAM located within the cytoplasmic domain of its associated gamma-chain. For example, in transfected epithelial cells and COS-1 cells, FcgammaRIIA mediates phagocytosis of IgG-coated red blood cells more efficiently than does FcgammaRI/gamma, and enhancement of phagocytosis by Syk kinase is more pronounced for FcgammaRI/gamma than for FcgammaRIIA. In addition, structure/function studies indicate that the gamma-chain ITAM and the FcgammaRIIA ITAM have different requirements for mediating the phagocytic signal. To study the differences between FcgammaRIIA and FcgammaRI/gamma, we examined the interaction of FcgammaRIIA and the FcgammaRI/gamma chimera FcgammaRI-gamma-gamma (extracellular domain-transmembrane domain-cytoplasmic domain) with Syk kinase and with the Src-related tyrosine kinases (SRTKs) Hck and Lyn in transfected COS-1 cells. Our data indicate that FcgammaRIIA interacts more readily with Syk than does FcgammaRI-gamma-gamma and suggest that one consequence may be the greater phagocytic efficiency of FcgammaRIIA compared with FcgammaRI/gamma. Furthermore, individual SRTKs affect the efficiency of phagocytosis differently for FcgammaRI-gamma-gamma and FcgammaRIIA and also influence the ability of these receptors to interact with Syk kinase. Taken together, the data suggest that differences in signaling by FcgammaRIIA and FcgammaRI-gamma-gamma are related in part to interaction with Syk and Src kinases and that individual SRTKs play different roles in FcgammaR-mediated phagocytosis.
A Simple Ontology of Manipulation Actions Based on Hand-Object Relations (2013)

Humans can perform a multitude of different actions with their hands (manipulations). In spite of this, so far there have been only a few attempts to represent manipulation types trying to understand the underlying principles. Here we first discuss how manipulation actions are structured in space and time. For this we use as temporal anchor points those moments where two objects (or hand and object) touch or un-touch each other during a manipulation. We show that by this one can define a relatively small tree-like manipulation ontology. We find less than 30 fundamental manipulations. The temporal anchors also provide us with information about when to pay attention to additional important information, for example when to consider trajectory shapes and relative poses between objects. As a consequence a highly condensed representation emerges by which different manipulations can be recognized and encoded. Examples of manipulations recognition and execution by a robot based on this representation are given at the end of this study.
Proteomics analysis reveals a Th17-prone cell population in presymptomatic graft-versus-host disease (2016)

Gastrointestinal graft-versus-host-disease (GI-GVHD) is a life-threatening complication occurring after allogeneic hematopoietic cell transplantation (HCT), and a blood biomarker that permits stratification of HCT patients according to their risk of developing GI-GVHD would greatly aid treatment planning. Through in-depth, large-scale proteomic profiling of presymptomatic samples, we identified a T cell population expressing both CD146, a cell adhesion molecule, and CCR5, a chemokine receptor that is upregulated as early as 14 days after transplantation in patients who develop GI-GVHD. The CD4<sup>+</sup>CD146<sup>+</sup>CCR5<sup>+</sup> T cell population is Th17 prone and increased by ICOS stimulation. shRNA knockdown of CD146 in T cells reduced their transmigration through endothelial cells, and maraviroc, a CCR5 inhibitor, reduced chemotaxis of the CD4<sup>+</sup>CD146<sup>+</sup>CCR5<sup>+</sup> T cell population toward CCL14. Mice that received CD146 shRNA-transduced human T cells did not lose weight, showed better survival, and had fewer CD4<sup>+</sup>CD146<sup>+</sup>CCR5<sup>+</sup> T cells and less pathogenic Th17 infiltration in the intestine, even compared with mice receiving maraviroc with control shRNA- transduced human T cells. Furthermore, the frequency of CD4<sup>+</sup>CD146<sup>+</sup>CCR5<sup>+</sup> Tregs was increased in GI-GVHD patients, and these cells showed increased plasticity toward Th17 upon ICOS stimulation. Our findings can be applied to early risk stratification, as well as specific preventative therapeutic strategies following HCT.
Longitudinal study of cerebrospinal fluid levels of tau, Aβ1–40, and Aβ1–42(43) in Alzheimer's disease: A study in Japan (1998)

To clarify the alterations of tau, amyloid beta protein (A beta) 1-40 and A beta1-42(43) in the cerebrospinal fluid (CSF) that accompany normal aging and the progression of Alzheimer's disease (AD), CSF samples of 93 AD patients, 32 longitudinal subjects among these 93 AD patients, 33 patients with non-AD dementia, 56 with other neurological diseases, and 54 normal control subjects from three independent institutes were analyzed by sensitive enzyme-linked immunosorbent assays. Although the tau levels increased with aging, a significant elevation of tau and a correlation between the tau levels and the clinical progression were observed in the AD patients. A significant decrease of the A beta1-42(43) levels and a significant increase of the ratio of A beta1-40 to A beta1-42(43) were observed in the AD patients. The longitudinal AD study showed continuous low A beta1-42(43) levels and an increase of the ratio of A beta1-40 to A beta1-42(43) before the onset of AD. These findings suggest that CSF tau may increase with the clinical progression of dementia and that the alteration of the CSF level of A beta1-42(43) and the ratio of A beta1-40 to A beta1-42(43) may start at early stages in AD. The assays of CSF tau, A beta1-40, and A beta1-42(43) provided efficient diagnostic sensitivity (71%) and specificity (83%) by using the production of tau levels and the ratio of A beta1-40 to A beta1-42(43), and an improvement in sensitivity (to 91%) was obtained in the longitudinal evaluation.
Factor VIIa-Tissue Factor: Functional Importance of Protein-Membrane Interactions (1997)

The first enzyme in the blood clotting cascade consists of two distinct protein subunits: a catalytic subunit (factor VIIa; FVIIa) and an essential regulatory subunit (tissue factor; TF). FVIIa is a soluble plasma protease, while TF is a cell-surface, integral-membrane protein. The recently reported X-ray crystal structure of the complex of FVIIa and the isolated extracellular domain of TF has provided important insights into the protein-protein interactions that bind these two subunits together (1). Equally important in the functioning of the TF-FVIIa complex, but much less well understood, are a series of protein-phospholipid interactions involving TF, FVIIa, and the natural substrates of this enzyme, as well as protein-protein interactions important in substrate recognition by TF-FVIIa. Here we review recent studies on the membrane organization and role of protein-phospholipid interactions in the function of TF-FVIIa, the enzyme that triggers blood clotting in hemostasis and thrombosis.
The Structure, Regulation, and Function of Human Matrix Metalloproteinase-13 (2002)

Matrix metalloproteinase-13 (MMP-13) is a proteolytic enzyme that belongs to a large family of extracellular matrix-degrading endopeptidases that are characterized by a zinc-binding motif at their catalytic sites. MMP-13 has a key role in the MMP activation cascade and appears to be critical in bone metabolism and homeostasis. It also has an important role in tumor invasion and metastasis. This commentary provides a detailed overview of the regulatory mechanisms, structure, and function of human MMP-13 and highlights the key factors involved in the biology of this important molecule.
Analysis of C3b/C3d binding sites and factor I cofactor regions within mouse complement receptors 1 and 2. (1994)

Human and murine CR1 and CR2 are defined as evolutionary homologues on the basis of their in vitro activities and a shared structural motif known as a short consensus repeat (SCR). To identify additional similarities between the two species, we analyzed the functional domains within the mouse receptors by constructing mouse-human chimeric cDNAs in which the C3 binding site of human CR2 has been replaced by different regions within the first eight SCRs of mouse CR1. Rosette analysis of cells expressing chimeric proteins, with erythrocytes bearing different mouse C3 fragments, coupled with rosette inhibition studies using specific anti-mouse CR1/CR2 mAbs reveal a weak C3b binding site within SCRs 1 and 2 of mouse CR1. There is no independent C3b interacting domain within SCRs 3 to 6, but their presence enhances C3 binding. A molecule that contains only the first six SCRs of mouse CR1 also binds C3b, but with less efficiency. There is no C3d binding area within the first six SCRs, but our data confirms previous studies indicating an additional C3b/C3d binding region within SCRs 7 and 8 of mouse CR1 (SCRs 1-2 of mouse CR2). The presence of SCRs 1 to 4 is required for C3 cofactor activity. 8C12, a mAb which blocks C3b erythrocyte rosette binding and the C3 cofactor activity of mouse CR1, binds only to chimeras containing SCRs 3 to 4.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of human immunodeficiency virus type 1 replication in vitro by a novel combination of anti-Tat single-chain intrabodies and NF-kappa B antagonists (1997)

Human immunodeficiency virus type 1 (HIV-1) Tat, an early regulatory protein that is critical for viral gene expression and replication, transactivates the HIV-1 long terminal repeat (LTR) via its binding to the transactivation response element (TAR) and, along with other cellular factors, increases viral transcription initiation and elongation. Tat also superactivates the HIV-1 promoter through a TAR-independent mechanism, including tumor necrosis factor alpha-induced and protein kinase C (PKC)-dependent activation of NF-kappa B, and inhibitors of Tat and NF-kappa B cooperatively down-regulate this Tat-mediated LTR superactivation. In this study, a combined pharmacologic and genetic strategy using two PKC (NF-kappa B) inhibitors, pentoxifylline (PTX) and Gö-6976, and a stably expressed anti-Tat single-chain intracellular antibody (sFv intrabody) was employed to obtain cooperative inhibition of both HIV-1 LTR-driven gene expression and HIV-1 replication. Treatment of cells with PTX and Gö-6976 resulted in cooperative inhibition of both HIV-1 LTR-driven gene expression and HIV-1 replication. In addition, the combined use of anti-Tat sFv intrabodies and the two NF-kappa B inhibitors retained the virus in the latent state for as long as 45 days. The combined treatment resulted in more durable inhibition of HIV-1 replication than was seen with the NF-kappa B inhibitors alone or the anti-Tat sFv intrabodies alone. Together, these results suggest that in future clinical gene therapy trials, a combined pharmacologic and genetic strategy like the one reported here may improve the survival of transduced cells and prolong clinical benefit.
Anti-tumor effects of allogeneic bone marrow transplantation in (NZB X NZW)F1 hybrids with spontaneous lymphosarcoma. (1984)

Untreated female (NZB X NZW)F1 hybrid mice (B/W F1) were found to develop lymphosarcoma spontaneously as they aged. Tumor incidence was evaluated in B/W F1 mice immunosuppressed with total lymphoid irradiation (TLI) and in TLI-conditioned B/W F1 mice reconstituted with 3 X 10(7) BALB/c bone marrow (BM) cells. BALB/C leads to B/W F1 chimerism (79 to 89% BALB/c-type cells) was confirmed by typing peripheral blood lymphocytes with specific alloantisera and complement by using a microcytotoxicity assay. Chimeras showed no clinical signs of graft-vs-host disease (GVHD). TLI-treated mice seemed to show a slightly accelerated onset of lymphosarcoma as compared with untreated controls, but the difference was not significant (p = 0.08). BALB/c leads to B/W F1 chimeras reconstituted at 1 to 3 mo of age (25 mice) developed no tumors for an observation period of 18 mo after transplantation. In contrast, tumors developed in 24/130 of age-matched controls, and in 13/57 of TLI-treated nonreconstituted age-matched B/W F1 mice. Tumor incidence in BALB/c leads to B/W F1 chimeras transplanted at an older age (9 to 11 mo) was similar to that observed in age-matched TLI-treated B/W F1 mice and age-matched untreated controls. The data suggests that the high naturally occurring incidence of lymphosarcoma could be reversed by reconstituting TLI-treated mice with BM cells (p = 0.027). Thus, allogeneic BM transplantation may exert potent graft-vs-tumor effects (GVT) when tumor susceptible hosts are reconstituted at an early age, whereas GVT is relatively ineffective at an advanced age, which probably correlates with an advanced stage of tumor development. Allogeneic BM transplantation should be additionally explored as a potential clinical tool for eradication of certain solid tumors in adjunct to high-dose radiochemotherapy, inasmuch as GVT seems to be independent of GVHD.
The Loan Market, Collateral, and Rates of Interest (1976)

This paper develops a theoretical model in which collateral is a mechanism for enforcing loan contracts. Collateral functions in two ways in the model. First, default on a loan triggers the loss of collateral value to the borrower, where this value is stochastic at the time when the loan is negotiated. The assignment of collateral provides incentive for the borrower to repay the loan. Second, default implies that the property nght to the collateral is transferred to the lender. The lender valuation of collateral, which may diverge from the borrower valuation, is also stochastic at the time of loan negotiation. The relation of lender to borrower valuation plays an important role in the loan process. If, because of costs of collection and marketing, moral hazard problems, or other types of costs, the lender valuation is much below the borrower valuation, then the process of default will entail dead-weight losses. Interest rates charged on loans will reflect these losses-appropriately weighted by the probability of default-and the expected interest charge paid by the borrower will be correspondingly above the underlying, transaction-cost-free rate of return. The more important these costs associated with default, the greater would be the dead-weight losses incurred and the amount of (otherwise) profitable loan opportunities foregone. Section 1 sets out the basic model and discusses the expected interest costs from the viewpoint of the borrower. Section 2 introduces transaction costs associated with default, discusses the expected interest return from the viewpoint of the lender, and analyzes the maximum size loan that would be issued by lenders on the basis of a given quantity of collateral. Section 3 uses the assumption that the lending industry yields a competitive rate of return to analyze the determination of
Use of an individual mandibular advancement device for an obstructive sleep apnoea patient with facial paralysis: a short‐term follow‐up case report (2012)

This case report aimed to describe the fabrication procedure and treatment efficacy of an individual, one-piece, non-adjustable mandibular advancement device (MAD) for a moderate obstructive sleep apnoea patient with facial paralysis (FP). Mandibular advancement device was fabricated with autopolymerising acrylic resin. The intermaxillary relations were recorded such as to fix the mandible at a protruded position with increased vertical dimension. Initial evaluation of the MAD was made with axial magnetic resonance imaging and polysomnography on the first day of usage. Following evaluations were made on the third and sixth month. After a follow-up period of 6 months, Apnoea/Hypopnea Index (AHI) significantly decreased from 26·7 to 3·0. However, the average oxygen saturation did not improve as expected initially. The MAD therapy decreased the AHI scores of a patient with FP. At the end of a follow-up period of 6 months, the patient did not report any serious complaint except temporary tooth pains.
High impedance fault detection utilizing incremental variance of normalized even order harmonic power (1991)

A novel method for the detection of high-impedance faults is proposed which uses the incremental variance of a normalized even order ratio measure. Staged fault tests were extensively carried out in Korean electric power systems. From the analysis of the staged fault test data, it was found that there exists an intermittent arcing phenomenon in most high-impedance faults and that the waveforms of this arcing fault current have an asymmetrical shape in each cycle. Based on these facts, three criteria, (even-order power, even-order ratio, and even-order incremental variance) for fault detection are presented, all of which are based on the changes of normalized even-order harmonic power in fault currents. These criteria are compared through the analysis of staged fault data and normal switching event data. It is shown that the even-order incremental variance criterion is superior to the other two criteria and that, with this criterion, high-impedance faults can be distinguished from normal switching events, including special loads such as electric furnaces and subways. Microprocessor-based protective relays, which can detect high-impedance faults by using the proposed methods, have been constructed, installed in Korea Electric Power Corporation substations, and tested during the last two years. Details of these field tests are given.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Neurotoxin-induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signaling (2012)

Individuals with Parkinson's disease (PD) experience a progressive decline in motor function as a result of selective loss of dopaminergic (DA) neurons in the substantia nigra. The mechanism(s) underlying the loss of DA neurons is not known. Here, we show that a neurotoxin that causes a disease that mimics PD upon administration to mice, because it induces the selective loss of DA neurons in the substantia nigra, alters Ca²⁺ homeostasis and induces ER stress. In a human neuroblastoma cell line, we found that endogenous store-operated Ca²⁺ entry (SOCE), which is critical for maintaining ER Ca²⁺ levels, is dependent on transient receptor potential channel 1 (TRPC1) activity. Neurotoxin treatment decreased TRPC1 expression, TRPC1 interaction with the SOCE modulator stromal interaction molecule 1 (STIM1), and Ca²⁺ entry into the cells. Overexpression of functional TRPC1 protected against neurotoxin-induced loss of SOCE, the associated decrease in ER Ca²⁺ levels, and the resultant unfolded protein response (UPR). In contrast, silencing of TRPC1 or STIM1 increased the UPR. Furthermore, Ca²⁺ entry via TRPC1 activated the AKT pathway, which has a known role in neuroprotection. Consistent with these in vitro data, Trpc1⁻/⁻ mice had an increased UPR and a reduced number of DA neurons. Brain lysates of patients with PD also showed an increased UPR and decreased TRPC1 levels. Importantly, overexpression of TRPC1 in mice restored AKT/mTOR signaling and increased DA neuron survival following neurotoxin administration. Overall, these results suggest that TRPC1 is involved in regulating Ca²⁺ homeostasis and inhibiting the UPR and thus contributes to neuronal survival.
Renin‐angiotensin system is an important factor in hormone refractory prostate cancer (2006)

The present data suggest that prostatic RAS is overexpressed in HRPC tissue, and expression of its components is influenced by several kinds of hormonal stimulation.
Chinese travellers to the United States — An emerging market (2000)

The study was designed to achieve a twofold objective. It examined the demographic and socioeconomic characteristics and trip-related attributes of outbound Chinese travellers to the United States. This particular market was then compared with Chinese visitors bound for nine Asia-Pacific countries and regions designated by the Chinese government as leisure travel destinations, and Chinese visitors to Japan and Western Europe. The purpose was to provide a profile of the US-bound Chinese market and identify a number of characteristics and attributes that significantly differentiated it from the other markets.