gebhart/patrepeval huggingface dataset:
Hydrophobic cluster analysis: An efficient new way to compare and analyse amino acid sequences (1987)

A new method for comparing and aligning protein sequences is described. This method, hydrophobic cluster analysis (HCA), relies upon a two-dimensional (2D) representation of the sequences. Hydrophobic clusters are determined in this 2D pattern and then used for the sequence comparisons. The method does not require powerful computer resources and can deal with distantly related proteins, even if no 3D data are available. This is illustrated in the present report by a comparison of human haemoglobin with leghaemoglobin, a comparison of the two domains of liver rhodanese (thiosulphate sulphurtransferase) and a comparison of plastocyanin and azurin.
Cloning, sequencing, and overexpression of genes for ribosomal proteins from Bacillus stearothermophilus. (1991)

Although a low resolution model for the arrangement of the proteins of the small and large ribosomal subunits is known, a detailed mechanistic understanding of the function of the ribosome awaits a high resolution structure of its components. While crystals have been obtained of several ribosomal proteins from Bacillus stearothermophilus, determination of atomic resolution structures of these proteins is impeded by the difficulty of obtaining large amounts of native proteins for crystallographic or NMR studies. We describe here the cloning and overexpression in Escherichia coli of the genes for ribosomal proteins S5, L6, L9, and L18 from B. stearothermophilus. S5 is extremely toxic to E. coli when overexpressed, and we have taken advantage of a new tightly regulated expression system to obtain high yields (more than 100 mg of pure protein/liter of culture) of this protein. The B. stearothermophilus S5 produced in E. coli crystallizes, and the crystals are identical to those obtained from the native protein. The crystals diffract to 2-A resolution.
Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression (2010)

B-cell chronic lymphocytic leukemia (B-CLL), the most common leukemia in the Western world, occurs in two forms, aggressive (showing for the most part high ZAP-70 expression and unmutated IgH V(H)) and indolent (showing low ZAP-70 expression and mutated IgH V(H)). We found that miR-29a is up-regulated in indolent human B-CLL as compared with aggressive B-CLL and normal CD19(+) B cells. To study the role of miR-29 in B-CLL, we generated Emu-miR-29 transgenic mice overexpressing miR-29 in mouse B cells. Flow cytometric analysis revealed a markedly expanded CD5(+) population in the spleen of these mice starting at 2 mo of age, with 85% (34/40) of miR-29 transgenic mice exhibiting expanded CD5(+) B-cell populations, a characteristic of B-CLL. On average, 50% of B cells in these transgenic mice were CD5 positive. At 2 y of age the mice showed significantly enlarged spleens and an increase in the CD5(+) B-cell population to approximately 100%. Of 20 Emu-miR-29 transgenic mice followed to 24-26 mo of age, 4 (20%) developed frank leukemia and died of the disease. These results suggest that dysregulation of miR-29 can contribute to the pathogenesis of indolent B-CLL.
Mouse Genome Informatics (MGI): reflecting on 25 years (2015)

From its inception in 1989, the mission of the Mouse Genome Informatics (MGI) resource remains to integrate genetic, genomic, and biological data about the laboratory mouse to facilitate the study of human health and disease. This mission is ever more feasible as the revolution in genetics knowledge, the ability to sequence genomes, and the ability to specifically manipulate mammalian genomes are now at our fingertips. Through major paradigm shifts in biological research and computer technologies, MGI has adapted and evolved to become an integral part of the larger global bioinformatics infrastructure and honed its ability to provide authoritative reference datasets used and incorporated by many other established bioinformatics resources. Here, we review some of the major changes in research approaches over that last quarter century, how these changes are reflected in the MGI resource you use today, and what may be around the next corner.
COSMOS: a compiled simulator for MOS circuits (1987)

The COSMOS simulator provides fast and accurate switch-level modeling of MOS digital circuits. It attains high performance by preprocessing the transistor network into a functionally equivalent Boolean representation. This description, produced by the symbolic analyzer ANAMOS, captures all aspects of switch-level networks including bidirectional transistors, stored charge, different signal strengths, and indeterminate (X) logic values. The LGCC program translates the Boolean representation into a set of machine language evaluation procedures and initialized data structures. These procedures and data structures are compiled along with code implementing the simulation kernel and user interface to produce the simulation program. The simulation program runs an order of magnitude faster than our previous simulator MOSSIM II.
Double-blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema (1999)

Although gamma-linolenic acid (GLA) has been shown to correct deficiencies in skin lipids associated with reduced delta-6-desaturase activity which should result in improvement of dysregulation of inflammation and immunity in atopic eczema, clinical studies with evening primrose oil containing 10% GLA have yielded contradictory results. We have therefore examined the effect of a higher percentage (at least 23%) GLA-containing borage oil in adults with stable atopic eczema of moderate severity in a double-blind, multicentre study. One hundred and sixty patients were randomized to take daily either 500 mg of borage oil-containing capsules or the bland lipid miglyol as a placebo over a 24-week period. Use of topical diflucortolone-21-valerate cream was allowed as rescue medication, with the amount used until response being defined as primary, and clinical improvement as secondary efficacy criteria. Although several clinical symptoms improved compared with placebo, the overall response to borage oil did not reach statistical significance. Significant differences in favour of borage oil were, however, observed in a subgroup excluding patients who failed to show increased erythrocyte dihomo-gamma-linolenic acid levels and in whom adherence to inclusion criteria and the study protocol were questionable. GLA metabolites increased in borage oil-treated patients only, and serum IgE showed a trend to decrease on overall and subgroup analysis. No substance-related adverse effects were observed. This study shows no overall efficacy of GLA-containing borage oil in atopic eczema, with steroid use being the primary response parameter, although it suggests that a subgroup of patients may benefit from this well-tolerated treatment.
Venoocclusive disease of the liver after marrow transplantation: Histological correlates of clinical signs and symptoms (1994)

We evaluated the relationship between the signs and symptoms of the clinical syndrome called veno-occlusive disease of the liver after bone marrow transplantation and the histological findings in 76 patients who later came to autopsy. Coded necropsy liver was scored for individual histological features that were correlated with prospectively assessed clinical features that the patients had exhibited during life. Patients were stratified into two groups: those with severe clinical veno-occlusive disease (n = 32) and those without. Clinically severe veno-occlusive disease was statistically correlated with several zone 3 acinar changes: occluded hepatic venules, the frequency of occluded hepatic venules x degree of occlusion, eccentric luminal narrowing/phlebosclerosis, zone 3 sinusoidal fibrosis and zone 3 hepatocyte necrosis (all p < or = 0.03). There was a significant relationship between the number of these histological abnormalities in zone 3 of the liver acinus and a clinical diagnosis of severe veno-occlusive disease (p = 0.003). The presence of ascites was significantly correlated with occluded venules, zone 3 sinusoidal fibrosis and zone 3 hepatocyte necrosis (p = 0.001). Maximum serum bilirubin in the first 20 days after transplant was significantly correlated with sinusoidal fibrosis, hepatocyte necrosis and eccentric luminal sclerosis/phlebosclerosis (p < 0.01) but not with venular occlusion. The clinical syndrome of liver toxicity (commonly called veno-occlusive disease) that results from cytoreductive therapy before bone marrow transplant is strongly correlated with a constellation of histological lesions involving structures in zone 3 of the liver acinus and the hepatic venules into which sinusoidal blood flows. This study suggests that there is no single diagnostic histological feature. The severity of clinical veno-occlusive disease appears to be proportional to the number of such histological changes and is not due solely to occlusion of small hepatic venules.
Alfred P. Sloan prize. Towards a biochemical description of malignant transformation: Identification and functional characterization of the rous sarcoma virus transforming gene product (1984)

I showed that a malignant sarcoma of chickens could be transmitted by a cell-free filtrate. Experiments with this virus or closely related descendents have continued to yield exciting new findings to this day. Although numerous papers have been published describing experiments on what came to be known as the Rous sarcoma virus (RSV), current modern molecular studies of viruses as agents that cause cancer began with two additional key developments. The first development was the demonstration by Manaker and Group;' in 1956 and by Temin and Rubin'" in 1958 that RSV could be grown to high titers in cultured chicken fibroblasts and could morphologically transform these cells; the number of transformed cells could be used to quantitate the amount of virus. The second development was the accumulation of genetic evidence that RSV camed a transforming gene, a gene that, when expressed, was responsible for malignant transformation. This gene was defined by the isolation and analysis of several mutants of RSV which had an altered capacity to transform cells. There are two classes of RSV mutants: (1) conditional mutants, which are temperature-sensitive for transformation; and (2) nonconditional mutants, which are inactive for transformation under all conditions. The first RSV temperature-sensitive mutants were isolated by Evidence published by Wang and coworkers4 in 1973 suggested that the nonconditional RSV mutants had deletions of the transforming gene. Biochemical studies revealed that the temperature-sensitive mutations occurred in the same region of the genome that was deleted in the nonconditional mutants.
Systemic lupus erythematosus (SLE) presenting as acute pancreatitis--a case report. (1996)

Acute pancreatitis is an uncommon manifestation of systemic lupus erythematosus (SLE). In most reported cases, it occurs in the setting of SLE with multi-organ involvement. We report an unusual case of SLE in a Sri Lankan woman presenting with acute pancreatitis with the pancreas as the sole major organ affected. The diagnosis of acute pancreatitis was based on clinical features, serum and urinary amylase levels and computerised tomography. She responded well to high-dose corticosteroid. We also review the literature and discuss the prevalence, theories of pathogenesis and treatment of this condition.
Antfarm: tracking processes in a virtual machine environment (2006)

In a virtualized environment, the VMM is the system’s primary resource manager. Some services usually implemented at the OS layer, like I/O scheduling or certain kinds of security monitoring, are therefore more naturally implemented inside the VMM. Implementing such services at the VMM layer can be complicated by the lack of OS and application-level knowledge within a VMM. This paper describes techniques that can be used by a VMM to independently overcome part of the “semantic gap ” separating it from the guest operating systems it supports. These techniques enable the VMM to track the existence and activities of operating system processes. Antfarm is an implementation of these techniques that works without detailed knowledge of a guest’s internal architecture or implementation. An evaluation of Antfarm for two virtualization environments and two operating systems shows that it can accurately infer process events while incurring only a small 2.5 % runtime overhead in the worst case. To demonstrate the practical benefits of process information in a VMM we implement an anticipatory disk scheduler at the VMM level. This case study shows that significant disk throughput improvements are possible in a virtualized environment by exploiting process information within a VMM. 1
Uric Acid Is a Danger Signal Activating NALP3 Inflammasome in Lung Injury Inflammation and Fibrosis (2009)

Uric acid released from injured cells constitutes a major endogenous danger signal that activates the NALP3 inflammasome, leading to IL-1beta production. Reducing uric acid tissue levels represents a novel therapeutic approach to control IL-1beta production and chronic inflammatory lung pathology.
Beyond Calculation: The Next Fifty Years of Computing (1997)

From the Publisher:
Bob Metcalfe is the inventor of the Ethernet technology and founder of the 3Com corporation. He is currently vice-president, technology at IDG and executive correspondent for Infoworld, where he writes a column that reaches over 500,000 readers worldwide. He holds a Ph.D. in Computer Science from Harvard.
Peter J. Denning is associate dean for computing and chair of the Computer Science Department in the School of Information Technology and Engineering at George Mason University. He was formerly the founding director of the Research Institute for Advanced Computer Science at the NASA Ames Research Center, and the president of the Association for Computing Machinery 1980-82.
This brilliantly eclectic collection, commissioned to celebrate a major milestone in an ongoing technological revolution, will fascinate anybody with an interest in computers and where they're taking us.
Induction of Antitumor Immunity by CTL Epitopes Genetically Linked to Membrane-Anchored β2-Microglobulin (2006)

Level and persistence of antigenic peptides presented by APCs on MHC class I (MHC-I) molecules influence the magnitude and quality of the ensuing CTL response. We recently demonstrated the unique immunological properties conferred on APCs by expressing beta2-microglobulin (beta2m) as an integral membrane protein. In this study, we explored membrane-anchored beta2m as a platform for cancer vaccines using as a model MO5, an OVA-expressing mouse B16 melanoma. We expressed in mouse RMA-S cells two H-2Kb binding peptides from MO5, OVA257-264, and TRP-2181-188, each genetically fused with the N terminus of membranal beta2m via a short linker. Specific Ab staining and T cell hybridoma activation confirmed that OVA257-264 was properly situated in the MHC-I binding groove. In vivo, transfectants expressing both peptides elicited stronger CTLs and conferred better protection against MO5 than peptide-saturated RMA-S cells. Cells expressing OVA257-264/beta2m were significantly superior to OVA257-264-charged cells in their ability to inhibit the growth of pre-established MO5 tumors. Our results highlight the immunotherapeutic potential of membranal beta2m as a universal scaffold for optimizing Ag presentation by MHC-I molecules.
Five-Lipoxygenase Products in Asthma (2013)

Overview Overview of the 5-Lipoxygenase Pathway, Jesper Z. Haeggstroem and Bengt Samuelsson Leukotriene Biochemistry 5-Lipoxygenase and 5-Lipoxygenase-Activating Protein, Jilly F. Evans Leukotriene C4 Synthase: A Pivotal Enzyme in the Biosynthesis of Cysteinyl Leukotrienes, John F. Penrose and K. Frank Austen Leukotriene A4 Hydrolase, Jesper Z. Haeggstroem Leukotriene Export in Human Leukocytes, Bing K. Lam Cell Biology of the Leukotrienes Pathways of Leukotriene Metabolism in Isolated Cell Models and Human Subjects, Robert C. Murphy and Pat Wheelan Cell Biology of the 5-Lipoxygenase Pathway: Amplification and Generation of Leukotrienes and Lipoxins by Transcellular Biosynthesis, Timothy D. Bigby, Bruce D. Levy, and Charles N. Serhan Physiological Actions of the Leukotrienes Leukotriene Receptors: Incompletely Defined Targets for Treatment of Asthma and Inflammation, Sven-Erik Dahlen Physiological Effects of the Leukotrienes in Humans, Neil C. Barnes and Lewis J. Smith Recovery of Leukotrienes Analysis of Leukotrienes and Lipoxins, Graham W. Taylor Measurement of Leukotrienes from Human Biological Fluids, Jay Y. Westcott and Ian K. Taylor Leukotrienes in Asthma Cysteinyl-Leukotriene Receptor Antagonism and 5-Lipoxygenase Inhibition in Asthma, S. M. Shuaib Nasser and Tak H. Lee Leukotriene Receptor Antagonism and Synthesis in Chronic Stable Asthma, Elliot Israel and Jeffrey M. Drazen Specific Drug Products Montelukast-An Antileukotriene Treatment for Asthma: Changing the Asthma-Treatment Paradigm, Beth C. Seidenberg and Theodore F. Reiss Pranlukast-The First Orally Active Cysteinyl Leukotriene Receptor Antagonist Marketed for the Treatment of Asthma, Jeffrey W. Dubb and Anthony S. Rebuck Zafirlukast, Catherine M. Bonuccelli and Trevor J. C. Higgins Zileuton: The First Leukotriene Synthesis Inhibitor for Use in the Management of Chronic Asthma, Louise M. Dube, Linda J. Swanson, Walid Awni, Rachel F. Ochs, Randy L. Bell, and George W. Carter Antileukotrienes in the Management of Asthma, Paul M. O'Byrne
Family Law: Cases, Comments and Questions. Second edition. By Harry D. Krause, Alumni Distinguished Professor of Law, University of Illinois. (American Casebook Series.) [St. Paul, Minnesota: West Publishing Co.1983. lxiii, 1178 and (Bibliography and Index) 43 pp. Hardback U.S. $26.95 net.] (1984)

Family Law: Cases, Comments and Questions. Second edition. By Harry D. Krause, Alumni Distinguished Professor of Law, University of Illinois. (American Casebook Series.) [St. Paul, Minnesota: West Publishing Co.1983. lxiii, 1178 and (Bibliography and Index) 43 pp. Hardback U.S. $26.95 net.] - Volume 43 Issue 2
Intracellular metabolism of indium-111-DTPA-labeled receptor targeted proteins. (1993)

The mechanisms of hepatic and renal accumulation and retention of 111In-labeled proteins has been the subject of many investigations. Because the lysosome is a common intracellular destination for a variety of agents including antibodies and polypeptide hormones, we studied the in vitro and in vivo metabolism of 111In-DTPA-labeled polypeptides using a series of glycoproteins that were concentrated within the lysosome by receptor mediated endocytosis. Indium-111-DTPA-labeled glycoproteins targeted to the mannose, asialoglycoprotein and mannose 6-phosphate receptors were studied in vitro using cell lines known to express these receptors and in vivo using Sprague-Dawley rats. Once internalized, the 111In label was released slowly with 60%-90% (depending on the cell type) of the activity remaining cell associated at 24 hr. Subcellular fractionation using Percoll gradients indicated that the activity remained within the lysosome. Following internalization of the 111In-DTPA-labeled glycoproteins, the label was rapidly converted to a low molecular weight species (estimated molecular weight < or = 1000 daltons). This conversion was not seen with 111In-DTPA-alpha-galactosidase. As a lysosomal enzyme, alpha-galactosidase is relatively resistant to proteolysis within the lysosome. These results suggest that following internalization, 111In-DTPA-polypeptides are delivered to the lysosome where the polypeptide backbone can be degraded to yield 111In-DTPA-amino acid(s). These metabolites remain within the lysosome and are only slowly released from the cell. The model systems used in these studies can also be used to evaluate the intracellular metabolism of polypeptides labeled by other techniques.
Control of antiviral defenses through hepatitis C virus disruption of retinoic acid-inducible gene-I signaling (2005)

Hepatitis C virus (HCV) is a major human pathogen that infects 170 million people. A hallmark of HCV is its ability to establish persistent infections reflecting the evasion of host immunity and interference with alpha/beta-IFN innate immune defenses. We demonstrate that disruption of retinoic acid-inducible gene I (RIG-I) signaling by the viral NS3/4A protease contributes to the ability of HCV to control innate antiviral defenses. RIG-I was essential for virus or HCV RNA-induced signaling to the IFN-beta promoter in human hepatoma cells. This signaling was disrupted by the protease activity of NS3/4A, which ablates RIG-I signaling of downstream IFN regulatory factor 3 and NF-kappaB activation, attenuating expression of host antiviral defense genes and interrupting an IFN amplification loop that otherwise suppresses HCV replication. Treatment of cells with an active site inhibitor of the NS3/4A protease relieved this suppression and restored intracellular antiviral defenses. Thus, NS3/4A control of RIG-I supports HCV persistence by preventing IFN regulatory factor 3 and NF-kappaB activation. Our results demonstrate that these processes are amenable to restoration through pharmacologic inhibition of viral protease function.
Evaluation of circadian control of intraocular pressure after a single drop of bimatoprost 0.03% or travoprost 0.004% (2008)

This marks the first time a single drop has been used for this type of evaluation. These findings suggest that both bimatoprost and travoprost provide comparable and lasting control of circadian IOP in patients with glaucoma or ocular hypertension.
Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress (2010)

Iron oxide nanoparticles with unique magnetic properties have a high potential for use in several biomedical, bioengineering and in vivo applications, including tissue repair, magnetic resonance imaging, immunoassay, drug delivery, detoxification of biologic fluids, cell sorting, and hyperthermia. Although various surface modifications are being done for making these nonbiodegradable nanoparticles more biocompatible, their toxic potential is still a major concern. The current in vitro study of the interaction of superparamagnetic iron oxide nanoparticles of mean diameter 30 nm coated with Tween 80 and murine macrophage (J774) cells was undertaken to evaluate the dose- and time-dependent toxic potential, as well as investigate the role of oxidative stress in the toxicity. A 15-30 nm size range of spherical nanoparticles were characterized by transmission electron microscopy and zeta sizer. MTT assay showed >95% viability of cells in lower concentrations (25-200 μg/mL) and up to three hours of exposure, whereas at higher concentrations (300-500 μg/mL) and prolonged (six hours) exposure viability reduced to 55%-65%. Necrosis-apoptosis assay by propidium iodide and Hoechst-33342 staining revealed loss of the majority of the cells by apoptosis. H₂DCFDDA assay to quantify generation of intracellular reactive oxygen species (ROS) indicated that exposure to a higher concentration of nanoparticles resulted in enhanced ROS generation, leading to cell injury and death. The cell membrane injury induced by nanoparticles studied using the lactate dehydrogenase assay, showed both concentration- and time-dependent damage. Thus, this study concluded that use of a low optimum concentration of superparamagnetic iron oxide nanoparticles is important for avoidance of oxidative stress-induced cell injury and death.