gebhart/patrepeval huggingface dataset:
ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions (2002)

Thrombotic thrombocytopenic purpura (TTP) is a devastating thrombotic disorder caused by widespread microvascular thrombi composed of platelets and von Willebrand factor (VWF). The disorder is associated with a deficiency of the VWF-cleaving metalloprotease, ADAMTS-13, with consequent accumulation of ultralarge (UL) VWF multimers in the plasma. ULVWF multimers, unlike plasma forms of VWF, attach spontaneously to platelet GP Ibalpha, a component of the GP Ib-IX-V complex. We have found that ULVWF multimers secreted from stimulated endothelial cells (ECs) remained anchored to the endothelial surface where platelets and Chinese hamster ovary cells expressing the GP Ib-IX-V complex attached to form long beads-on-a-string structures in the presence of fluid shear stresses in both the venous (2.5 dyne/cm(2)) and arterial (20 and 50 dyne/cm(2)) ranges. Although measurement of the activity of the ADAMTS-13 VWF-cleaving metalloprotease in vitro requires prolonged incubation of the enzyme with VWF under nonphysiologic conditions, EC-derived ULVWF strings with attached platelets were cleaved within seconds to minutes in the presence of normal plasma (containing approximately 100% ADAMTS-13 activity) or in the presence of partially purified ADAMTS-13. By contrast, the strings persisted for the entire period of perfusion (10 minutes) in the presence of plasma from patients with TTP containing 0% to 10% ADAMTS-13 activity. These results suggest that cleavage of EC-derived ULVWF multimers by ADAMTS-13 is a rapid physiologic process that occurs on endothelial cell surfaces.
Is Fusion Necessary After Anterior Cervical Discectomy? (1996)

Anterior cervical discectomy is an effective and reliable treatment for nerve root or cord compression caused by disc herniation or spondylosis. Although physicians have traditionally included fusion as a part of this procedure, recent experience has suggested that this may not be necessary. Dr. Volker Sonntag and Dr. Peter Klara express opposing views on the need for fusion after discectomy and support their perspectives with clinical experience and a review of the pathoanatomy of disc disease. Dr. Sonntag believes that the majority of patients are well served with discectomy alone, avoiding the complications of graft harvest and potential nonunion. Dr. Klara feels that the interposed graft restores foraminal height and maintains cervical lordosis, both of which are important to a good outcome.
Nonlinear Dimensionality Reduction by Locally Linear Embedding (2000)

Many areas of science depend on exploratory data analysis and visualization. The need to analyze large amounts of multivariate data raises the fundamental problem of dimensionality reduction: how to discover compact representations of high-dimensional data. Here, we introduce locally linear embedding (LLE), an unsupervised learning algorithm that computes low-dimensional, neighborhood-preserving embeddings of high-dimensional inputs. Unlike clustering methods for local dimensionality reduction, LLE maps its inputs into a single global coordinate system of lower dimensionality, and its optimizations do not involve local minima. By exploiting the local symmetries of linear reconstructions, LLE is able to learn the global structure of nonlinear manifolds, such as those generated by images of faces or documents of text.
Blockade of Notch Signaling Ameliorates Murine Collagen-Induced Arthritis via Suppressing Th1 and Th17 Cell Responses (2014)

Recent studies have demonstrated that Notch signaling is critically involved in the regulation of immune response and contributes to autoimmune pathogenesis. Here, Notch signaling was found to be activated in CD4(+) T cells and synovial tissue from collagen-induced arthritis mice. In vivo administration of the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT) substantially reduced the severity of arthritic symptoms and joint damage in collagen-induced arthritis mice. Notably, DAPT treatment significantly suppressed Th1- and Th17-cell responses in spleen and lymph nodes and reduced IFN-γ and IL-17 levels in plasma. In polarization culture, DAPT treatment markedly reduced Th17 cell expansion from naïve T cells, whereas fusion protein of the Notch receptor ligand delta-like 3 significantly increased the frequency and absolute number of Th17 cells. These results suggest a novel therapeutic strategy for treatment of human rheumatoid arthritis by targeting Notch signaling using γ-secretase inhibitors.
Interleukin-4 induces the synthesis and secretion of MCP-1/JE by human endothelial cells. (1991)

The authors have demonstrated that human interleukin-4 (IL-4) induces increased expression of the mRNA encoding the monocyte-specific chemoattractant and activator, MCP-1/JE, in human endothelial cells (EC). In addition, treatment of ECs with IL-4 resulted in the synthesis and secretion of MCP-1/JE protein. While IL-4 did not significantly influence the induced expression of MCP-1/JE mRNA by interleukin-1 (IL-1) or tumor necrosis factor, concomitant treatment with IL-4 and IL-1 caused more secretion of MCP-1/JE protein than either cytokine alone. These results suggest that EC-produced MCP-1/JE may mediate some of IL-4's effects on monocyte physiology in vivo, including IL-4's anti-tumor properties.
Interference Suppression in Wireless Cellular Networks through Picocells (2007)

It has been demonstrated that base station cooperation can reduce co-channel interference (CCI) and increase cellular system capacity. In this work, we consider another approach by dividing the system into picocells through denser base station deployment. For a two-dimensional hexagon cellular array and the propagation model under consideration, we observe that the operating regime shifts from interference-limited to noise-limited when the density increases to about 20 base stations per km <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . To compare the performance of both approaches, we adopt a criterion to maximize the minimum served spectral efficiency with a certain user outage constraint. Simulations show that denser base station deployment outperforms suboptimal cooperation schemes (zero-forcing) when the density increases beyond 3~12 base stations per km <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , the exact value depending on the rules of outage user selection. However, close-to-optimal cooperation schemes (zero-forcing with dirty-paper-coding) are always superior to denser base station deployment.
Dynamics of Intracellular Movement and Nucleocytoplasmic Recycling of the Ligand-Activated Androgen Receptor in Living Cells (2000)

An expression construct containing the cDNA encoding a modified aequorea green fluorescent protein (GFP) ligated to the 5'-end of the rat androgen receptor (AR) cDNA (GFP-AR) was used to study the intracellular dynamics of the receptor movement in living cells. In three different cell lines, ie. PC3, HeLa, and COS1, unliganded GFP-AR was seen mostly in the cytoplasm and rapidly (within 15-60 min) moved to the nuclear compartment after androgen treatment. Upon androgen withdrawal, the labeled AR migrated back to the cytoplasmic compartment and maintained its ability to reenter the nucleus on subsequent exposure to androgen. Under the condition of inhibited protein synthesis by cycloheximide (50 microg/ml), at least four rounds of receptor recycling after androgen treatment and withdrawal were recorded. Two nonandrogenic hormones, 17beta-estradiol and progesterone at higher concentrations (10(-7)/10(-6) M), were able to both transactivate the AR-responsive promoter and translocate the GFP-AR into the nucleus. Similarly, antiandrogenic ligands, cyproterone acetate and casodex, were also capable of translocating the cytoplasmic AR into the nucleus albeit at a slower rate than the androgen 5alpha-dihydrotestosterone (DHT). All AR ligands with transactivation potential, including the mixed agonist/antagonist cyproterone acetate, caused translocation of the GFP-AR into a subnuclear compartment indicated by its punctate intranuclear distribution. However, translocation caused by casodex, a pure antagonist, resulted in a homogeneous nuclear distribution. Subsequent exposure of the casodex-treated cell to DHT rapidly (15-30 min) altered the homogeneous to punctate distribution of the already translocated nuclear AR. When transported into the nucleus either by casodex or by DHT, GFP-AR was resistant to 2 M NaCl extraction, indicating that the homogeneously distributed AR is also associated with the nuclear matrix. Taken together, these results demonstrate that AR requires ligand activation for its nuclear translocation where occupancy by only agonists and partial agonists can direct it to a potentially functional subnuclear location and that one receptor molecule can undertake multiple rounds of hormonal signaling; this indicates that ligand dissociation/inactivation rather than receptor degradation may play a critical role in terminating hormone action.
THE ABILITY OF PRETRANSPLANT TEST-DOSE PHARMACOKINETIC PROFILES TO REDUCE EARLY ADVERSE EVENTS AFTER RENAL TRANSPLANTATION1, 2 (1992)

Pretransplant test-dose pharmacokinetic profiles were used to determine individual cyclosporine drug bioavailability and clearance rates in renal transplant patients. Assuming a linear relation between dose and area under the concentration curve (AUC), starting i.v. and p.o. CsA doses were computed from the test-dose results. Target values were 400 ng/ml steady-state concentration (Css) during continuous intravenous infusion, and 500 ng/ml average drug concentration (Cavss = AUC/dosing interval) after oral administration, based upon measurements with the specific monoclonal antibody 3H-tracer radioimmunoassay. The outcomes after dose individualization with a 1-(n = 32), 2-(n = 38), or 3-(n = 41) hr i.v. infusion test dose and a p.o. test dose (n = 111) were compared with 228 historical control patients who received a uniform protocol of CsA i.v. at 2.5 mg/kg/day and p.o. at 14 mg/kg/day. The observed Css after i.v. CsA was within 10% of the target concentration in 73% of recipients tested with the 3-hr protocol, a significantly greater fraction than achieved with either the uniform dose (14%), or the 1-(34%) and 2-(25%) hr protocols. Patients in the 3-hr protocol group showed reduced incidences of delayed graft function, early graft loss, and rejection episodes, and a lower mean serum creatinine value, particularly at 7 but also at 30 days posttransplantation. Administration of the predicted oral dose produced a peak concentration of greater than or equal to 700 ng/ml drug absorption in 60% of recipients at 3 days, 90% at 5 days, and 98% at 7 days. The test-dose method less effectively predicted the appropriate oral CsA dose to produce target Cssav and failed to reduce the 90-day rejection incidence. Despite its limitations with the more-complicated p.o. route, the test-dose method successfully predicts i.v. CsA doses, thereby reducing the incidence of early adverse events.
Transforming growth factor-beta2 antibody attenuates fibrosis in the experimental diabetic rat kidney (2001)

Diabetic nephropathy is characterised by an increase in glomerular and tubular fibrosis that compromises kidney function. The transforming growth factor-betas (TGF-betas) have been shown to play a major role in fibrosis and we have shown that TGF-beta2, in particular, increases co-ordinately with fibrogenesis in the diabetic kidney. The aim of this study was to investigate the changes in expression of extracellular matrix molecules in the diabetic kidney, with and without systemic administration of a recombinant human monoclonal antibody to TGF-beta2. Streptozotocin-induced diabetic rats were split into two groups. The first were treated with 5 mg/kg irrelevant control IgG4 (placebo) and the second treated with 5 mg/kg isoform-specific recombinant monoclonal anti-TGF-beta2 IgG4 (termed CAT-152) systemically every second day for 14 days. A further group of six non-diabetic rats was also used as a control. Various biological parameters were measured daily throughout the experimental period, and on termination of the experiment at 14 days Western blotting was performed on kidney cortices for procollagen-I C-propeptide, which is an indicator of the rate of collagen-I synthesis within the kidney. In the placebo-treated diabetic rats, blood glucose, food consumption, urinary albumin excretion (UAE) and kidney weights were all significantly higher than in the non-diabetic group (P<0.05, n=24, by ANOVA). In the anti-TGF-beta2-treated diabetic rats, kidney weights and UAE levels were decreased when compared with those in placebo-treated diabetics. Western blotting for the procollagen-I C-propeptide in kidney cortices showed a significant increase in levels in placebo-treated diabetic rats compared with non-diabetic controls over the 14 day diabetic period, indicating initiation of fibrogenesis. By contrast, in anti-TGF-beta2-treated diabetic rats, levels of the propeptide remained at non-diabetic levels. In summary, a significant suppression of kidney fibrosis was seen in anti-TGF-beta2-treated diabetic rats, compared with placebo-treated diabetic rats. We conclude that systemic delivery of CAT-152, a neutralising anti-TGF-beta2 antibody, during the acute stages of diabetic nephropathy reduces the rate of pathogenic fibrosis in the kidney.
[Value of a percutaneous estrogen solution in stopping lactation]. (1990)

An open trial involving 121 women was carried out to compare the efficacy and safety of a percutaneous estrogen solution and of an anti-prolactin solution. The complete inhibition of the let-down of milk was slightly less frequently obtained with the Percutacrine Oestrogénique that with Parlodel. The efficacy of Percutacrine Oestrogénique was linked to two conditions of administration: administration soon after delivery and compliance with the dosage, which was less frequently achieved than with Parlodel. In contrast, the clinical safety of Percutacrine Oestrogénique was excellent, and significantly better than that of Parlodel, notably with regard to dizziness (p less than 0.001 for the first 5 days of treatment). The incidence of the depressive tendency commonly observed post-partum was lower in the group of women receiving Percutacrine Oestrogénique, and reached the level of significance after 10 days of treatment.
Cloning and characterization of a mouse IL-12 receptor-β component (1995)

Using DNA cross-hybridization, we have isolated and characterized cDNA clones encoding a mouse (mo) IL-12R beta component. Two forms of cDNA were found. The first form encodes a receptor protein that has an overall structure very similar to that of the known human (hu) IL-12R beta with 54% amino acid identity, whereas in the second type of mouse cDNA, the equivalent of the transmembrane region has been deleted. This presumed alternative splicing event also gives rise to a frame shift that results in a receptor with an identical extracellular domain but a different C-terminal sequence. Whether this alternative C terminus is capable of signaling is not yet known. Both types of receptors when expressed in COS-7 cells are membrane associated and bind moIL-12 with an affinity of 1 nM, similar to the affinity of huIL-12R beta for huIL-12. The monomeric size of both moIL-12R beta proteins is about 100 kDa. Similar to huIL-12R beta, moIL-12R beta is expressed at the surface of COS-7 and Ba/F3 cells as a dimer/oligomer whose formation is independent of IL-12 binding. When expressed in Ba/F3 cells, moIL-12R beta binds moIL-12 with two affinities of 50 and 470 pM, corresponding to the medium and high affinity IL-12 binding sites previously identified on mouse Con A lymphoblasts. Despite the higher affinity displayed by the moIL-12R beta in Ba/F3 cells, this receptor alone is not sufficient to transduce a signal, suggesting that another subunit is probably required to generate a functional moIL-12R complex.
Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice (2014)

High-dose ionizing irradiation (IR) results in direct tumor cell death and augments tumor-specific immunity, which enhances tumor control both locally and distantly. Unfortunately, local relapses often occur following IR treatment, indicating that IR-induced responses are inadequate to maintain antitumor immunity. Therapeutic blockade of the T cell negative regulator programmed death-ligand 1 (PD-L1, also called B7-H1) can enhance T cell effector function when PD-L1 is expressed in chronically inflamed tissues and tumors. Here, we demonstrate that PD-L1 was upregulated in the tumor microenvironment after IR. Administration of anti-PD-L1 enhanced the efficacy of IR through a cytotoxic T cell-dependent mechanism. Concomitant with IR-mediated tumor regression, we observed that IR and anti-PD-L1 synergistically reduced the local accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs), which suppress T cells and alter the tumor immune microenvironment. Furthermore, activation of cytotoxic T cells with combination therapy mediated the reduction of MDSCs in tumors through the cytotoxic actions of TNF. Our data provide evidence for a close interaction between IR, T cells, and the PD-L1/PD-1 axis and establish a basis for the rational design of combination therapy with immune modulators and radiotherapy.
Antigenicity and immunogenicity of collagen (2004)

Pertinent issues of collagen antigenicity and immunogenicity are concisely reviewed as they relate to the design and application of biomedical devices. A brief discussion of the fundamental concepts of collagen immunochemistry is presented, with a subsequent review of documented clinical responses to devices containing reconstituted soluble or solubilized collagen. The significance of atelocollagen, concerns regarding collagen-induced autoimmunity, and other relevant topics are also addressed in the context of current understanding of the human immune response to collagen.
Robust hybrid control for autonomous vehicle motion planning (2002)

The operation of an autonomous vehicle in an unknown, dynamic environment is a very complex problem, especially when the vehicle is required to use its full maneuvering capabilities, and to react in real time to changes in the operational environment. A possible approach to reduce the computational complexity of the motion planning problem for a nonlinear, high dimensional system, is based on a quantization of the system dynamics, leading to a control architecture based on a hybrid automaton, the states of which represent feasible trajectory primitives for the vehicle. The paper focuses on the feasibility of this approach, in the presence of disturbances and uncertainties in the plant and/or in the environment: the structure of a robust hybrid automaton is defined and its properties are analyzed. In particular, we address the issues of well-posedness, consistency and reachability. For the case of autonomous vehicles, we provide sufficient conditions to guarantee reachability of the automaton.
Immunohistochemical analysis of TrkA neurotrophin receptor expression in human non‐neuronal carcinomas (1998)

The Trk family of tyrosine protein kinase receptors plays a significant role in the development and maintenance of neural tissues. It has been recently shown that Trk receptors are also expressed by a wide range of normal non-neuronal tissues in humans in a cell type-specific manner. In the present study, the expression patterns of TrkA in 337 non-neuronal invasive carcinomas of 15 different human tissues were investigated immunohistochemically. Overall, 133 (39%), 101 (30%) and 103 (31%) tumors exhibited strong, moderate and no TrkA immunoreactivity, respectively. Esophageal and thyroid carcinomas expressed high levels of TrkA, whereas the levels in gastric and colon cancers were low. TrkA expression was detected not only in carcinomas originating from TrkA-positive normal counterpart tissues, including the esophagus, breast, lung and uterus, but also in those from TrkA-negative tissues/cells of the thyroid, liver and ovary. Immunostaining for nerve growth factor-beta, the specific ligand for TrkA, in esophageal and breast carcinomas demonstrated its immunoreactivity in stromal fibroblasts and some TrkA-expressing tumor cells. These results suggest that paracrine/autocrine regulation via stromal/tumoral NGF-tumoral TrkA interaction may be involved in the growth of certain non-neuronal carcinomas.
Cellular mechanisms for heavy metal detoxification and tolerance (2002)

Heavy metals such as Cu and Zn are essential for normal plant growth, although elevated concentrations of both essential and non-essential metals can result in growth inhibition and toxicity symptoms. Plants possess a range of potential cellular mechanisms that may be involved in the detoxification of heavy metals and thus tolerance to metal stress. These include roles for the following: for mycorrhiza and for binding to cell wall and extracellular exudates; for reduced uptake or efflux pumping of metals at the plasma membrane; for chelation of metals in the cytosol by peptides such as phytochelatins; for the repair of stress-damaged proteins; and for the compartmentation of metals in the vacuole by tonoplast-located transporters. This review provides a broad overview of the evidence for an involvement of each mechanism in heavy metal detoxification and tolerance.
Mechanisms of adrenoceptor desensitisation in the failing human heart (1994)

Journal Article Mechanisms of β adrenoceptor desensitisation in the failing human heart Get access Sian E Harding, Sian E Harding Department of Cardiac Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom: S E Harding, L A Brown, D G Wynne, C H Davies, P A Poole-Wilson. Correspondence to Dr Harding. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lesley A Brown, Lesley A Brown Department of Cardiac Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom: S E Harding, L A Brown, D G Wynne, C H Davies, P A Poole-Wilson. Correspondence to Dr Harding. Search for other works by this author on: Oxford Academic PubMed Google Scholar Dylan G Wynne, Dylan G Wynne Department of Cardiac Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom: S E Harding, L A Brown, D G Wynne, C H Davies, P A Poole-Wilson. Correspondence to Dr Harding. Search for other works by this author on: Oxford Academic PubMed Google Scholar Crispin H Davies, Crispin H Davies Department of Cardiac Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom: S E Harding, L A Brown, D G Wynne, C H Davies, P A Poole-Wilson. Correspondence to Dr Harding. Search for other works by this author on: Oxford Academic PubMed Google Scholar Philip A Poole-Wilson Philip A Poole-Wilson Department of Cardiac Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom: S E Harding, L A Brown, D G Wynne, C H Davies, P A Poole-Wilson. Correspondence to Dr Harding. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 10, October 1994, Pages 1451–1460, https://doi.org/10.1093/cvr/28.10.1451 Published: 01 October 1994 Article history Received: 03 February 1994 Accepted: 21 April 1994 Published: 01 October 1994