gebhart/patrepeval huggingface dataset:
Alcohol-induced free radicals in mice: Direct toxicants or signaling molecules? (2001)

Tumor necrosis factor alpha (TNF-alpha) and free radicals are produced in early alcohol-induced liver injury. Recently, pathology caused by alcohol was blocked nearly completely in tumor necrosis factor alpha receptor 1 (TNF-R1) knockout mice. With this model, it is now possible to evaluate whether free radicals are directly toxic or act as redox regulators of TNF-alpha production. Specifically, if free radicals were directly toxic, a parallel decrease in free radicals and pathology in TNF-R1 knockout mice would be predicted. If they only affect TNF-alpha production, radicals would be expected to remain high while pathology is diminished. Accordingly, free radical production in TNF-R1 knockout mice was studied here. The enteral alcohol delivery model used mice lacking TNF-R1 (p55) and wild-type control C57Bl/6J mice. Animals received a liquid diet continuously with either ethanol or isocaloric maltose-dextrin as control for 4 weeks. Urine ethanol levels fluctuated from 10 to 500 mg/dL in a cyclic pattern in mice receiving ethanol. Ethanol elevated liver:body weight ratios, serum alanine transaminase (ALT) levels, and pathology scores in wild-type mice. These parameters were blunted nearly completely in TNF-R1 knockout mice. Ethanol treatment increased free radical production in wild-type mice compared with animals fed a high-fat control diet. There were no differences in intensity of free radical signals regardless of the presence or absence of TNF-R1; however, pathology differed markedly between these groups. These findings are consistent with the hypothesis that free radicals act as redox signals for TNF-alpha production and do not directly damage cells in early alcohol-induced hepatic injury.
TNF Family Member B Cell-Activating Factor (BAFF) Receptor-Dependent and -Independent Roles for BAFF in B Cell Physiology (2004)

The cytokine TNF family member B cell-activating factor (BAFF; also termed BLyS) is essential for B cell generation and maintenance. Three receptors have been identified that bind to BAFF: transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI); B cell maturation Ag (BCMA); and BAFF-R. Recently, it was shown that A/WySnJ mice, which contain a dramatically reduced peripheral B cell compartment due to decreased B cell life span, express a mutant BAFF-R. This finding, together with normal or enhanced B cell generation in mice deficient for BCMA or TACI, respectively, suggested that the interaction of BAFF with BAFF-R triggers signals essential for the generation and maintenance of mature B cells. However, B cells in mice deficient for BAFF differ phenotypically and functionally from A/WySnJ B cells. Residual signaling through the mutant BAFF-R could account for these differences. Alternatively, dominant-negative interference by the mutant receptor could lead to an overestimation of the importance of BAFF-R. To resolve this issue, we generated BAFF-R-null mice. Baff-r(-/-) mice display strongly reduced late transitional and follicular B cell numbers and are essentially devoid of marginal zone B cells. Overexpression of Bcl-2 rescues mature B cell development in Baff-r(-/-) mice, suggesting that BAFF-R mediates a survival signal. CD21 and CD23 surface expression are reduced on mature Baff-r(-/-) B cells, but not to the same extent as on mature B cells in BAFF-deficient mice. In addition, we found that Baff-r(-/-) mice mount significant, but reduced, Ag-specific Ab responses and are able to form spontaneous germinal centers in mesenteric lymph nodes. The reduction in Ab titers correlates with the reduced B cell numbers in the mutant mice.
Privacy preserving error resilient dna searching through oblivious automata (2007)

Human Desoxyribo-Nucleic Acid (DNA) sequences offer a wealth of information that reveal, among others, predisposition to various diseases and paternity relations. The breadth and personalized nature of this information highlights the need for privacy-preserving protocols. In this paper, we present a new error-resilient privacy-preserving string searching protocol that is suitable for running private DNA queries. This protocol checks if a short template (e.g., a string that describes a mutation leading to a disease), known to one party, is present inside a DNA sequence owned by another party, accounting for possible errors and without disclosing to each party the other party's input. Each query is formulated as a regular expression over a finite alphabet and implemented as an automaton. As the main technical contribution, we provide a protocol that allows to execute any finite state machine in an oblivious manner, requiring a communication complexity which is linear both in the number of states and the length of the input string.
Human protein reference database--2006 update (2005)

Human Protein Reference Database (HPRD) (http://www.hprd.org) was developed to serve as a comprehensive collection of protein features, post-translational modifications (PTMs) and protein-protein interactions. Since the original report, this database has increased to >20 000 proteins entries and has become the largest database for literature-derived protein-protein interactions (>30 000) and PTMs (>8000) for human proteins. We have also introduced several new features in HPRD including: (i) protein isoforms, (ii) enhanced search options, (iii) linking of pathway annotations and (iv) integration of a novel browser, GenProt Viewer (http://www.genprot.org), developed by us that allows integration of genomic and proteomic information. With the continued support and active participation by the biomedical community, we expect HPRD to become a unique source of curated information for the human proteome and spur biomedical discoveries based on integration of genomic, transcriptomic and proteomic data.
Effects of tamoxifen and interferon-β or the combination on tumor-induced angiogenesis (1997)

Inhibition of angiogenesis by anti-tumor agents may play a role in tumor growth arrest. Tamoxifen and interferon-alpha/beta (IFN-alpha/beta) exhibit potentiated anti-proliferative activity against tumor cells. However, additional host-mediated effects such as modulation of angiogenesis may also inhibit tumor growth in vivo. The effect of tamoxifen and IFN-beta on angiogenesis induced by 2 human tumors, MCF-7 breast carcinoma (estradiol dependent) and NIH-OVCAR-3 ovarian carcinoma (estradiol independent), was assessed. Treatment of nude mice bearing MCF-7 tumors with tamoxifen resulted in a 68% decrease in the number of vessels at the tumor periphery. Treatment with IFN-beta yielded a 33% reduction. Treatment of nude mice bearing NIH-OVCAR-3 tumors with tamoxifen resulted in a 73% decrease in the number of vessels. Treatment with IFN-beta yielded a 57% reduction. Combination treatment resulted in augmented anti-angiogenic effects. As single agents, both tamoxifen and IFN-beta inhibited xenograft tumor growth. Ten weeks of tamoxifen treatment resulted in growth inhibition of MCF-7 and NIH-OVCAR-3 carcinomas by 85% and 66%, respectively. Ten weeks of IFN-beta treatment resulted in inhibition of growth of MCF-7 and NIH-OVCAR-3 carcinomas by 67% and 88%, respectively. The combination of tamoxifen and IFN-beta completely prevented growth of MCF-7 and NIH-OVCAR-3 carcinomas. The anti-angiogenic effects of tamoxifen and IFN-beta were additive. Inhibition of angiogenesis was detectable before measurable effects on tumor volume in both MCF-7 and NIH-OVCAR-3 tumors. Potentiation of anti-angiogenic effects by tamoxifen and IFN-beta, possibly resulting from enhanced IFN-induced gene expression, may contribute to anti-tumor activity in both estradiol-dependent and estradiol-independent tumors in vivo.
Cord Blood Transplantation Study (COBLT): Cord Blood Bank Standard Operating Procedures (1998)

In 1995, the National Heart Lung and Blood Institute (NHLBI) solicited requests for a proposal (RFP) entitled "Transplant Centers for Clinical Research on Transplantation of Umbilical Cord Stem and Progenitor Cells." Three banks, six transplant centers, and one medical coordinating center (MCC) (Table 1) were funded with the overall goal of banking cord blood units (CBU) using a single manual of operations. Furthermore, the clinical protocols to evaluate the transplant outcome for adult and pediatric recipients of these well-characterized CBU would be analyzed in a uniform fashion. Because of the intense interest of the transplantation community in the policies and procedures for cord blood collection and processing, the principal investigators of the cord blood banks (CBB) and NHLBI elected to submit for publication the rationale and an abridged, but detailed, version of the standard operating procedures (SOP) developed between October 1996 and July 1998 prior to the initiation of the clinical protocols to be performed with these CBU. As the SOP will be refined over time, the complete SOP and subsequent amendments will be published and continually updated on the websites from the MCC-The EMMES Corporation (www.EMMES.com). All forms referred to in this document may be obtained from the EMMES website. It is hoped that the publication of this document will lay down a framework that will not only facilitate the development of other CBB but also help us more rapidly define what constitutes an "acceptable" CBU product.
Renin–angiotensin system, natriuretic peptides, obesity, metabolic syndrome, and hypertension: an integrated view in humans (2008)

The obesity pandemic is closely related to hypertension and metabolic syndrome. Visceral adipose tissue plays a key role in the metabolic and cardiovascular complications of being overweight. The pathophysiological link between visceral adiposity and cardiometabolic complications focuses on insulin sensitivity, sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS) and, only recently, on cardiac natriuretic peptide system (CNPS). RAAS and CNPS are endogenous antagonistic systems on sodium balance, cardiovascular system, and metabolism. The circulating RAAS is dysregulated in obese patients, and adipose tissue has a full local renin-angiotensin system that is active at local and systemic level. Adipocyte biology and metabolism are influenced by local renin-angiotensin system, with angiotensin II acting as a 'growth factor' for adipocytes. CNPS induces natriuresis and diuresis, reduces blood pressure, and, moreover, has powerful lipolytic and lipomobilizing activity in humans but not in rodents. In obesity, lower plasmatic natriuretic peptides levels with increasing BMI, waist circumference, and metabolic syndrome have been documented. Thus, reduced CNPS effects coupled with increased RAAS activity have a central role in obesity and its deadly complications. We propose herein an integrated view of the dysregulation of these two antagonistic systems in human obesity complicated with hypertension, metabolic syndrome, and increased cardiovascular risk.
Use of Liposome-Associated Bupivacaine for the Management of a Chronic Pain Syndrome (1994)

Lafont, Noelle D. MD; Boogaerts, Jean G. MD, rhD; Legros, Franz J. PhD Author Information
Efficient algorithm for time-optimal control of a two-link manipulator (1990)

A class of optimization problems of interest in the field of robotics is one that seeks to minimize the time required to force a manipulator to travel a specified distance. Robots employ multiple, bounded control inputs. This work describes a new, very fast algorithm for determining minimum-time trajectories for such systems. We have modified the steepest descent method of optimal programming to find time-optimal switch times for bang-bang control systems. The Switch Time Optimization (STO) program has been applied to a two-link manipulator with two control inputs. To find the minimum time for a robot end-effector to travel between two points in its workspace, one must establish the optimal position of the robot with respect to the work station. The algorithm accomplishes this by allowing optimal initial states to be determined along with the time history of the controls. Exact control switch times and optimal initial conditions have been found for minimum-time repositioning maneuvers in which the robot was required to travel a specified distance. The STO algorithm is not limited to use with manipulators; it is applicable to any bang-bang system.
Interleukin 2 dependence of human natural killer (NK) cell activity. (1983)

When purified populations of human natural killer (NK) cells were tested for cytotoxic activity in the presence of partially purified preparations of human interleukin 2 (IL 2), a definite, dose-dependent linear increase in reactivity was observed. To determine whether such augmentation by IL 2 might reflect an important aspect of the physiologic regulation of NK activity, we examined the effects of monoclonal antibodies against human IL 2 on spontaneous NK activity. The presence of such antibodies during the 4-hr cytotoxicity assay resulted in significant inhibition of NK activity, and when the NK cells were pretreated for 16 to 20 hr with anti-IL 2, little or no activity remained. These data suggest that the spontaneous cytotoxic activity of NK cells is dependent on their continued exposure to IL 2. The reduction in NK activity resulting from treatment with anti-IL 2 could be at least partially restored by exposure to only low amounts of partially purified IL 2. These data have provided the basis for formulating a novel model of NK cell activation.
Safety, Pharmacokinetics, and Antitumor Activity of AMG 386, a Selective Angiopoietin Inhibitor, in Adult Patients With Advanced Solid Tumors (2009)

PURPOSE AMG 386 is an investigational peptide-Fc fusion protein (ie, peptibody) that inhibits angiogenesis by preventing the interaction of angiopoietin-1 and angiopoietin-2 with their receptor, Tie2. This first-in-human study evaluated the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of AMG 386 in adults with advanced solid tumors. PATIENTS AND METHODS Patients in sequential cohorts received weekly intravenous AMG 386 doses of 0.3, 1, 3, 10, or 30 mg/kg. Results Thirty-two patients were enrolled on the study and received AMG 386. One occurrence of dose-limiting toxicity was seen at 30 mg/kg: respiratory arrest, which likely was caused by tumor burden that was possibly related to AMG 386. The most common toxicities were fatigue and peripheral edema. Proteinuria (n = 11) was observed without clinical sequelae. Only four patients (12%) experienced treatment-related toxicities greater than grade 1. A maximum-tolerated dose was not reached. PK was dose-linear and the mean terminal-phase elimination half-life values ranged from 3.1 to 6.3 days. Serum AMG 386 levels appeared to reach steady-state after four weekly doses, and there was minimal accumulation. No anti-AMG 386 neutralizing antibodies were detected. Reductions in volume transfer constant (K(trans); measured by dynamic contrast-enhanced magnetic resonance imaging) were observed in 10 patients (13 lesions) 48 hours to 8 weeks after treatment. One patient with refractory ovarian cancer achieved a confirmed partial response (ie, 32.5% reduction by Response Evaluation Criteria in Solid Tumors) and withdrew from the study with a partial response after 156 weeks of treatment; four patients experienced stable disease for at least 16 weeks. CONCLUSION Weekly AMG 386 appeared well tolerated, and its safety profile appeared distinct from that of vascular endothelial growth factor-axis inhibitors. AMG 386 also appeared to impact tumor vascularity and showed antitumor activity in this patient population.
The biomechanics and motor control of human gait (1987)

Obstructive jaundice occurring in a patient with portal hypertension is a rare association. In this report, a 24-year-old patient is described who had biliary obstruction due to a portal cavernoma compressing the common bile duct and in whom surgical decompression of the portal system resulted in relief of the biliary obstruction, thus proving that the dilated portal vein collaterals were compressing the biliary tract and producing jaundice. Although biliary obstruction due to a portal cavernoma has been described earlier, this is, to the best of our knowledge, the first case described in which improvement followed shunt surgery.
Optomechanical Wavelength and Energy Conversion in High-QDouble-Layer Cavities of Photonic Crystal Slabs (2006)

We demonstrate that ultrasmall double-layer photonic-crystal-slab cavities exhibit a very high-Q value for a wide range of the layer spacing, which enables us to realize unique optomechanical coupling. By mechanically varying the separation, we can achieve extraordinarily large wavelength conversion. In addition, the light stored in the cavity can generate a large radiation force. We show that this system exhibits extremely high energy conversion efficiency between optical and mechanical energy, leading to a novel approach for the optomechanical control of light and matter.
From Disease Association to Risk Assessment: An Optimistic View from Genome-Wide Association Studies on Type 1 Diabetes (2009)

Genome-wide association studies (GWAS) have been fruitful in identifying disease susceptibility loci for common and complex diseases. A remaining question is whether we can quantify individual disease risk based on genotype data, in order to facilitate personalized prevention and treatment for complex diseases. Previous studies have typically failed to achieve satisfactory performance, primarily due to the use of only a limited number of confirmed susceptibility loci. Here we propose that sophisticated machine-learning approaches with a large ensemble of markers may improve the performance of disease risk assessment. We applied a Support Vector Machine (SVM) algorithm on a GWAS dataset generated on the Affymetrix genotyping platform for type 1 diabetes (T1D) and optimized a risk assessment model with hundreds of markers. We subsequently tested this model on an independent Illumina-genotyped dataset with imputed genotypes (1,008 cases and 1,000 controls), as well as a separate Affymetrix-genotyped dataset (1,529 cases and 1,458 controls), resulting in area under ROC curve (AUC) of approximately 0.84 in both datasets. In contrast, poor performance was achieved when limited to dozens of known susceptibility loci in the SVM model or logistic regression model. Our study suggests that improved disease risk assessment can be achieved by using algorithms that take into account interactions between a large ensemble of markers. We are optimistic that genotype-based disease risk assessment may be feasible for diseases where a notable proportion of the risk has already been captured by SNP arrays.
A meta-analysis of the association of IRF5 polymorphism with systemic lupus erythematosus (2011)

To more precisely estimate the association between interferon regulatory factor 5 (IRF5) polymorphisms and systemic lupus erythematosus (SLE) risk, we surveyed studies on the association of IRF5 rs2204640, rs10954213, rs729302 or rs2280714 with SLE using PubMed, Embase and Web of Science up to February 2011. Two investigators independently assessed the data quality and extracted the data. A total of 17 comparisons from ten relevant studies involving 6403 patients and 7475 controls were included to analyse the association between IRF5 rs2004640 and SLE risk (odds ratio, OR = 1.41, 95% confidence interval (CI) 1.34-1.49, P = 0.000). As for rs10954213, there were ten comparisons from six relevant studies involving 3461 patients and 3692 controls were included to analyse the association between IRF5 rs10954213 and SLE risk (OR = 1.23, 95% CI 1.08-1.39, P = 0.002). And this meta-analysis also showed a significant association of rs729302 (OR = 0.78, 95% CI 0.74-0.83, P = 0.000), rs2280714 (OR = 0.90, 95% CI 0.83-0.98, P = 0.021) with SLE. In a subgroup analysis by ethnicity, significantly increased SLE risk was associated with IRF5 rs2004640 T allele in populations of European, Asian and Latin American origin, and the rs10954213 A allele is significantly associated with SLE in European origin but not in Asian origin. This meta-analysis suggested that IRF5 gene polymorphism was associated with SLE in multiple ethnic populations.
COBRA, an Arabidopsis Extracellular Glycosyl-Phosphatidyl Inositol-Anchored Protein, Specifically Controls Highly Anisotropic Expansion through Its Involvement in Cellulose Microfibril Orientation (2005)

The orientation of cell expansion is a process at the heart of plant morphogenesis. Cellulose microfibrils are the primary anisotropic material in the cell wall and thus are likely to be the main determinant of the orientation of cell expansion. COBRA (COB) has been identified previously as a potential regulator of cellulose biogenesis. In this study, characterization of a null allele, cob-4, establishes the key role of COB in controlling anisotropic expansion in most developing organs. Quantitative polarized-light and field-emission scanning electron microscopy reveal that loss of anisotropic expansion in cob mutants is accompanied by disorganization of the orientation of cellulose microfibrils and subsequent reduction of crystalline cellulose. Analyses of the conditional cob-1 allele suggested that COB is primarily implicated in microfibril deposition during rapid elongation. Immunodetection analysis in elongating root cells revealed that, in agreement with its substitution by a glycosylphosphatidylinositol anchor, COB was polarly targeted to both the plasma membrane and the longitudinal cell walls and was distributed in a banding pattern perpendicular to the longitudinal axis via a microtubule-dependent mechanism. Our observations suggest that COB, through its involvement in cellulose microfibril orientation, is an essential factor in highly anisotropic expansion during plant morphogenesis.
Dactylocyclines, novel tetracycline derivatives produced by a Dactylosporangium sp. II. Structure elucidation. (1992)

Fermentation of Dactylosporangium sp. (ATCC 53693) produces a mixture of tetracycline derivatives from which several related tetracycline glycosides, the dactylocyclines, were isolated and their structures determined. The most abundant glycoside in initial fermentations was found to be dactylocycline A. Each glycoside proved to be acid sensitive and readily hydrolyzed to a common aglycone, dactylocyclinone. While the aglycone was cross resistant with tetracycline, the dactylocyclines proved active against certain tetracycline-resistant organisms.