gebhart/patrepeval huggingface dataset:
Current and emerging strategies for the treatment and management of systemic lupus erythematosus based on molecular signatures of acute and chronic inflammation (2010)

Abstract: Lupus is a chronic, systemic inflammatory condition in which eicosanoids, cytokines, nitric oxide (NO), a deranged immune system, and genetics play a significant role. Our studies revealed that an imbalance in the pro- and antioxidants and NO and an alteration in the metabolism of essential fatty acids exist in lupus. The current strategy of management includes administration of nonsteroidal anti-inflammatory drugs such as hydroxychloroquine and immunosuppressive drugs such as corticosteroids. Investigational drugs include the following: 1) belimumab, a fully human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, also known as B-cell-activation factor of the TNF family; 2) stem cell transplantation; 3) rituximab, a chimeric monoclonal antibody against CD20, which is primarily found on the surface of B-cells and can therefore destroy B-cells; and 4) IL-27, which has potent anti-inflammatory actions. Our studies showed that a regimen of corticosteroids and cyclophosphamide, and methods designed to enhance endothelial NO synthesis and augment antioxidant defenses, led to induction of long-lasting remission of the disease. These results suggest that methods designed to modulate molecular signatures of the disease process and suppress inflammation could be of significant benefit in lupus. Some of these strategies could be vagal nerve stimulation, glucose–insulin infusion, and administration of lipoxins, resolvins, protectins, and nitrolipids by themselves or their stable synthetic analogs that are known to suppress inflammation and help in the resolution and healing of the inflammation-induced damage. These strategies are likely to be useful not only in lupus but also in other conditions, such as rheumatoid arthritis, scleroderma, ischemia-reperfusion injury to the myocardium, ischemic heart disease, and sepsis. Keywords: lupus, lipoxins, resolvins, polyunsaturated fatty acids, free radicals, rheumatology
The Motion and Precipitation of Suspensoids in Divergent Electric Fields (1951)

The motion of suspensoid particles relative to that of the solvent resulting from polarization forces produced by an inhomogeneous electric field is defined as ``dielectrophoresis.'' It is analogous to the related phenomenon of electrophoresis, in which motion of suspensoid particles is produced by the action of an electrostatic field on the charged particles. From a consideration of theoretical calculations and from experimental observations it is concluded that the phenomena of ``dielectrophoresis'' and ``dielectro-precipitation'' can be observed under rather ideal conditions, though it is ordinarily often difficult to do so because of the presence of the more easily produced electrophoresis or ion-type migration of charged particles. The usefulness of dielectrophoresis (and/or electrophoresis) for removing suspended solid particles from polymer solutions during analysis is described.
Atrial Ultrastructural Changes During Experimental Atrial Tachycardia Depend on High Ventricular Rate (2004)

Structural remodeling during chronic atrial tachycardia is related to the concomitant presence of a high ventricular rate and hence the occurrence of congestive heart failure rather than a high atrial rate. Electrical remodeling can occur in the absence of significant structural changes.
Bst DNA polymerase permits rapid sequence analysis from nanogram amounts of template. (1991)

A simple, rapid method is presented for the enzymatic sequence analysis of nanogram amounts of single-stranded or double-stranded DNA. This approach employs the thermostable DNA polymerase from Bacillus sterothermophilus and exploits its ability to efficiently extend all of the template-primer complex, even at low substrate concentrations. The procedure requires few pipetting steps, no preannealing step and very short reaction time. This method can significantly reduce the cost associated with DNA polymerase and the amount of template and time required to perform the enzymatic sequencing reactions. As little as a 10-ng aliquot of such sequencing reactions can be analyzed on a fluorescence-based capillary gel electrophoresis instrument recently developed in our laboratory. This highly sensitive detection, in conjunction with the ability to efficiently sequence nanogram amounts of template, strongly suggests the feasibility of direct DNA sequencing of single bacteriophage M13 plaques without prior amplification.
Oxidative Burst Capability of Human Monocyte Subsets Defined by High and Low Hla-Dr Expression (1989)

There is a wide range in the expression of major histocompatability complex (MHC) class II HLA-DR molecules on freshly isolated human peripheral blood monocytes from one individual. This study determined whether the variability in HLA-DR expression on monocytes correlated with their oxidative burst capability after treatment with either phorbol myristate acetate (PMA) or calcium ionophore A23187. Freshly obtained cells were incubated with 2',7'-dichlorofluorescin diacetate (DCFH-DA), a dye which is utilized for the determination of cell oxidative potential by flow cytometry. Cells were stimulated, and then stained with phycoerythrin (PE)-labeled monoclonal antibodies (mAb). Two-color flow cytometry was used to determine changes in DCFH-DA (green) fluorescence which corresponded to oxidative product formation by cells which stained only with the PE-labeled mAb (monocytes). While monocytes with a high or low surface density of HLA-DR differed substantially in HLA-DR expression, only small differences in oxidative capability between "high" and "low" subsets were observed. Thus, monocytes which are very different in HLA-DR expression possess very similar oxidative burst capabilities.
Proteolytic Activities of Two Types of Mannose-Binding Lectin-Associated Serine Protease (2000)

Mannose (or mannan)-binding lectin (MBL) is an oligomeric serum lectin that plays a role in innate immunity by activating the complement system. In human, two types of MBL-associated serine protease (MASP-1 and MASP-2) and a truncated protein of MASP-2 (small MBL-associated protein; sMAP or MAp19) are complexed with MBL. To clarify the proteolytic activities of MASP-1 and MASP-2 against C4, C2, and C3, we isolated these two types of MASP in activated forms from human serum by sequential affinity chromatography. On an anti-MASP-1 column, MASP-2 passed through the column in the presence of EDTA and high salt concentration, whereas MASP-1 was retained. Isolated MASP-1 and MASP-2 exhibited proteolytic activities against C3 and C4, respectively. C2 was activated by both MASPs. C1 inhibitor (C1 INH), an inhibitor for C1r and C1s, formed equimolar complexes with MASP-1 and MASP-2 and inhibited their proteolytic activities.
Targeting MET in cancer therapy (2017)

<i>MET</i> encodes a receptor tyrosine kinase c-MET for hepatocyte growth factor (HGF). The specific combination of c-MET and HGF activates downstream signaling pathways to trigger cell migration, proliferation, and angiogenesis. <i>MET</i> exon 14 alterations and <i>MET</i> gene amplification play a critical role in the origin of cancer. Several monoclonal antibodies and small-molecule inhibitors of c-MET have been evaluated in clinical trials. In patients with advanced non-small cell lung cancer, cabozantinib and crizotinib showed clear efficacy with a generally tolerable adverse events profile. In gastrointestinal cancers, most phase III trials of MET inhibitors showed negative results. In hepatocellular carcinoma, based on the encouraging results of some phase II studies, a series of phase III trials are currently recruiting patients to access the efficacy and safety of <i>MET</i> inhibitors.
Progression of Atheroma (2002)

Traditional thinking accorded a major role to deranged cell proliferation as a determinant of the abnormal cellularity of atheroma. However, studies conducted in several laboratories have documented the occurrence of disordered apoptosis during atherogenesis, leading to the death of lipid-rich foam cells (promoting lipid-core formation) and depletion of vascular smooth muscle cells (fostering fragility of the fibrous cap). A complex interplay of environmental factors and endogenous proteins regulates apoptosis and contributes to the struggle between cell death and procreation in atherosclerosis. In addition to a variety of growth factors, chemically modified lipids, reactive oxygen species, proinflammatory cytokines, and Fas ligand produced by activated immune cells may influence cell viability through a diversity of pathways, including the caspase cascade, the Bcl-2 protein family, and the oncogene/antioncogene system. A clarification of the molecular mechanisms responsible for vascular cell death may aid in the development of novel therapeutic strategies to treat atherosclerosis and its complications, including the acute coronary syndromes.
Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes (2009)

The naive phenotype of cord blood (CB) T cells may reduce graft-versus-host disease after umbilical cord blood transplantation, but this naivety and their low absolute numbers also delays immune reconstitution, producing higher infection-related mortality that is predominantly related to CMV, adenovirus (Adv), and EBV. Adoptive immunotherapy with peripheral blood-derived virus-specific cytotoxic T lymphocytes (CTLs) can effectively prevent viral disease after conventional stem cell transplantation, and we now describe the generation of single cultures of CTLs from CB that are specific for multiple viruses. Using EBV-infected B cells transduced with a clinical-grade Ad5f35CMVpp65 adenoviral vector as sources of EBV, Adv, and CMV antigens, we expanded virus-specific T cells even from CB T cells with a naive phenotype. After expansion, each CTL culture contained both CD8(+) and CD4(+) T-cell subsets, predominantly of effector memory phenotype. Each CTL culture also had HLA-restricted virus-specific cytotoxic effector function against EBV, CMV, and Adv targets. The CB CTLs recognized multiple viral epitopes, including CD4-restricted Adv-hexon epitopes and immunosubdominant CD4- and CD8-restricted CMVpp65 epitopes. Notwithstanding their naive phenotype, it is therefore possible to generate trivirus-specific CTLs in a single culture of CB, which may be of value to prevent or treat viral disease in CB transplant recipients. This study is registered at www.clinicaltrials.gov as NCT00078533.
Histological and Hormonal Characteristic of Microencapsulated Human Parathyroid Tissue in the Remote Terms after Xenotransplantation to Rats with Experimental Hypoparathyroidism (2011)

Microencapsulated human parathyroid tissue preserves the viability and high ability to secrete parathormone in the remote terms after transplantation to rats with experimental hypoparathyroidism, which suggests good prospects for using this tissue in the presence of compensated hypofunctional state of parathyroid system in clinical practice.
Learning from Dyadic Data (1998)

Dyadic data refers to a domain with two finite sets of objects in which observations are made for dyads, i.e., pairs with one element from either set. This type of data arises naturally in many application ranging from computational linguistics and information retrieval to preference analysis and computer vision. In this paper, we present a systematic, domain-independent framework of learning from dyadic data by statistical mixturemodels. Our approach covers different models with flat and hierarchical latent class structures. We propose an annealed version of the standard EM algorithm for model fitting which is empirically evaluated on a variety of data sets from different domains.
Expression of two Trichoderma reesei endoglucanases in the yeast Saccharomyces cerevisiae (1987)

The cDNA copies of the two endo-beta-1,4-glucanase genes, egl1 and egl3, from the filamentous fungus Trichoderma reesei were expressed in yeast Saccharomyces cerevisiae under the control of the yeast phosphoglycerate kinase gene promoter. Active EGI and EGIII enzyme was produced and secreted by yeast into the growth medium. The recombinant EGI enzyme was larger and more heterogeneous in size than the native enzyme secreted by Trichoderma, due to differences in the extent of N-glycosylation between these two organisms. The morphology of the yeast cells producing EGI or EGIII was clearly different from control strain.
Ex post and ex ante analysis of provisional data (1999)

In this paper we suggest a framework to assess the degree of reliability of provisional estimates as forecasts of final data, and we re-examine the question of the most appropriate way in which available data should be used for ex ante forecasting in the presence of a data-revision process. Various desirable properties for provisional data are suggested, as well as procedures for testing them, taking into account the possible non-stationarity of economic variables. For illustration, the methodology is applied to assess the quality of the US M1 data production process and to derive a conditional model whose performance in forecasting is then tested against other alternatives based on simple transformations of provisional data or of past final data. Copyright © 1999 John Wiley & Sons, Ltd.
Apoptosis Signal-Regulating Kinase-1 Is Involved in Vascular Endothelial and Cardiac Remodeling Caused by Nitric Oxide Deficiency (2007)

Long-term treatment with N(omega)-nitro-l-arginine methylester (l-NAME), an NO synthase inhibitor, induces hypertension and cardiovascular injury. However, its precise mechanism is unknown. Using apoptosis signal-regulating kinase-1 (ASK1)-deficient mice, we investigated the role of ASK1 in cardiovascular injury caused by l-NAME treatment. l-NAME was orally administered to ASK1-deficient and C57BL/6J (wild) mice for 8 weeks. l-NAME treatment increased blood pressure of wild and ASK1-deficient mice to a similar extent, indicating no role of ASK1 in NO-deficient hypertension. l-NAME treatment significantly impaired acetylcholine-induced carotid arterial relaxation in wild mice (P<0.01), being associated with the decreased endothelial NO synthase (eNOS) activity (P<0.01) and the increased disruption of eNOS dimer (P<0.01), whereas these changes by l-NAME were substantially attenuated in ASK1-deficient mice. Thus, ASK1 is involved in the impairment of vascular endothelial function by reducing eNOS activity and disrupting eNOS dimer. l-NAME treatment increased vascular reduced nicotinamide-adenine dinucleotide phosphate oxidase activity and superoxide in wild mice to a greater extent than in ASK1 deficient mice. l-NAME treatment in wild mice caused cardiac hypertrophy, myocyte apoptosis, macrophage infiltration, coronary arterial remodeling, interstitial fibrosis, and the expression of monocyte chemoattractant protein-1 and transforming growth factor-beta1, whereas these cardiac changes by l-NAME were absent in ASK1-deficient mice. Cardiac reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and superoxide elevation by l-NAME were much less in ASK1-deficient mice than in wild mice. Our work provided the first evidence that ASK1 is implicated in vascular endothelial dysfunction and cardiovascular remodeling induced by NO deficiency by regulating eNOS and reduced nicotinamide-adenine dinucleotide phosphate oxidase.
Dose-Dense Chemotherapy Improves Mechanisms of Antitumor Immune Response (2012)

Abstract Dose-dense (DD) regimens of combination chemotherapy may produce superior clinical outcomes, but the basis for these effects are not completely clear. In this study, we assessed whether a DD combinatorial regimen of low-dose cisplatin and paclitaxel produces superior immune-mediated efficacy when compared with a maximum tolerated dose (MTD) regimen in treating platinum-resistant ovarian cancer as modeled in mice. Immune responses generated by the DD regimen were identified with regard to the immune cell subset responsible for the antitumor effects observed. The DD regimen was less toxic to the immune system, reduced immunosuppression by the tumor microenvironment, and triggered recruitment of macrophages and tumor-specific CD8+ T-cell responses to tumors [as determined by interleukin (IL)-2 and IFN-γ secretion]. In this model, we found that the DD regimen exerted greater therapeutic effects than the MTD regimen, justifying its further clinical investigation. Fourteen patients with platinum-resistant relapse of ovarian cancer received DD chemotherapy consisting of weekly carboplatin (AUC2) and paclitaxel (60–80 mg/m2) as the third- or fourth-line treatment. Serum was collected over the course of treatment, and serial IFN-γ and IL-2 levels were used to determine CD8+ T-cell activation. Of the four patients with disease control, three had serum levels of IL-2 and IFN-γ associated with cytotoxic CD8+ T-cell activity. The therapeutic effect of the DD chemotherapy relied on the preservation of the immune system and the treatment-mediated promotion of tumor-specific immunity, especially the antitumor CD8+ T-cell response. Because the DD regimen controlled drug-resistant disease through a novel immune mechanism, it may offer a fine strategy for salvage treatment. Cancer Res; 73(1); 119–27. ©2012 AACR.
Using RNAi in the clinic. (2006)

RNA interference (RNAi) is a biological process that controls gene silencing in all living cells. Targeting the RNAi system represents a novel therapeutic strategy that has the ability to intercede with multiple disease-related genes and so target many human diseases. Recently, the design of small interfering RNA (siRNA)-selective compounds has become more straightforward because of the significant progress made in predictive modeling. Exciting new data show that siRNA blocks gene function in vivo, suggesting that it has potential as a therapeutic approach for humans. This article highlights recent advances in siRNA research and discusses the aims of the pharmaceutical and biotechnology industries to progress siRNA compounds into the clinical. In the fight against disease, the use of RNAi is a powerful new tactic that adds to the arsenal of small-molecule inhibitors and antibody-blocking approaches.
Mutant ataxin-3 promotes the autophagic degradation of parkin (2011)

There is growing evidence that autophagy plays a key role in neurodegenerative diseases. For instance, stimulating autophagy is neuroprotective both in vitro and in vivo in models of trinucleotide-repeat diseases such as Machado-Joseph disease (MJD). Similarly, proteins associated with familial forms of Parkinson disease (PD) such as parkin and PINK1 converge on the autophagy pathway. Yet, despite these shared mechanisms, it is not clear whether or how these disorders are related at a molecular level. We reported that the mutant form of ataxin-3, the protein responsible for MJD, promotes the autophagic degradation of parkin. Given that the loss of parkin function leads to PD, we propose that the increased turnover of parkin triggered by mutant ataxin-3 may explain some of the parkinsonian features observed in MJD. Moreover, the findings suggest that an increased clearance of parkin in MJD could mitigate the otherwise beneficial effects of autophagy in neurodegeneration.
Improving the Specificity of Recombinant Immunoassays for Lyme Disease (2003)

A recent paper by Hefty et al. ([3][1]) identified recombinant lipoproteins OspE and ElpB1 from Borrelia burgdorferi as potential aids in the serodiagnosis of Lyme disease. However, the use of recombinant FlaB and OspC, in addition to the above antigens, may have been prematurely rejected by the
Imbalance of regulatory T cells in human autoimmune diseases (2005)

The breakdown of mechanisms assuring the recognition of self and non-self is a hallmark feature of autoimmune diseases. In the past 10 years, there has been a steadily increasing interest in a subpopulation of regulatory T cells, which exert their suppressive function in vitro in a contact-dependent manner and preferentially express high levels of CD25 and forkhead and winged-helix family transcription factor forkhead box P3 (FOXP3) (TREGs). Recent findings of changed prevalences and functional efficiencies indicate that these TREGs play a unique role in autoimmune diseases. Clinical findings in patients with mutated FOXP3 genes and a specific polymorphism in the promotor region of FOXP3 also support the role of FOXP3 as a 'master control gene' in the development and functioning of TREGs. Both altered generation of TREGs and insufficient suppression of inflammation in autoimmune diseases are considered to be crucial for the initiation and perpetuation of disease. TREG-related somatic cell therapy is considered as an intriguing new intervention to approach autoimmune diseases.
The Influence of Water-soluble Polymers and pH on Hydroxypropyl-β-Cyclodextrin Complexation of Drugs (1996)

AbstractThe effect of water-soluble polymers and ionization of the drug molecules on the cyclodextrin, mainly 2-hydroxypropyl-β-cyclodextrin (HPβCD), solubilization of drugs was investigated. HPβCD has significant solubilizing effect on acetazolamide, prazepam, and sulfamethoxazole in aqueous solutions. All three polymers tested-i.e., hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP), and carboxymethylcellulose-increase the solubilizing effect of HPβCD. The polymers increase the solubilization by increasing the apparent stability constant (Kc of the drug-HPβCD complex. Thus, addition of 0.10% (w/v) HPMC to the aqueous complexation medium results in a 56% increase in K, for the acetazolamide-HPβCD complex and a 200% increase in Kc for the prazepam-HPβCD complex. Addition of 0.25% (w/v) PVP to the complexation medium results in a 138% increase in K for the sulfamethoxazole-HPβCD complex. The HPβCD solubilization of the drugs can also be improved by ionization of the drug molecule through pH adjustments. However, larger improvements of the HPβCD solubilization are obtained when both methods are used simultaneously compared to when either method is used separately.
Recent developments in surface studies of GaN and AlN (2005)

Recent developments in the structural analysis of GaN and AlN surfaces are reviewed, and the implications of these structures for molecular beam epitaxial growth are discussed. The GaN(0001), AlN(0001), and GaN(101¯0) surfaces are all found to be terminated by metallic layers containing approximately one bilayer of Ga or Al atoms. However, in contrast to GaN(0001) where the Ga bilayer exists in an incommensurate, fluid-like state at room temperature, the metallic layers for AlN(0001) and GaN(101¯0) form large-unit-cell commensurate structures with static atomic arrangements. Small amounts of H on the GaN(0001) surface leads to facet formation on the surface, whereas larger amounts of H produce a 2×2 surface arrangement that displaces the Ga bilayer. A possible model for the H-terminated GaN(101¯1) surface is introduced and first-principles total energy calculations employing a finite temperature thermodynamics approach are employed to determine the conditions in which it could be stable.
Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810 (2016)

Clinicaltrials.gov NCT02383212. Registered 2 February 2015.