gebhart/patrepeval huggingface dataset:
Current understanding of fatty acid biosynthesis and the acyl carrier protein (2010)

FA (fatty acid) synthesis represents a central, conserved process by which acyl chains are produced for utilization in a number of end-products such as biological membranes. Central to FA synthesis, the ACP (acyl carrier protein) represents the cofactor protein that covalently binds all fatty acyl intermediates via a phosphopantetheine linker during the synthesis process. FASs (FA synthases) can be divided into two classes, type I and II, which are primarily present in eukaryotes and bacteria/plants respectively. They are characterized by being composed of either large multifunctional polypeptides in the case of type I or consisting of discretely expressed mono-functional proteins in the type II system. Owing to this difference in architecture, the FAS system has been thought to be a good target for the discovery of novel antibacterial agents, as exemplified by the antituberculosis drug isoniazid. There have been considerable advances in this field in recent years, including the first high-resolution structural insights into the type I mega-synthases and their dynamic behaviour. Furthermore, the structural and dynamic properties of an increasing number of acyl-ACPs have been described, leading to an improved comprehension of this central carrier protein. In the present review we discuss the state of the understanding of FA synthesis with a focus on ACP. In particular, developments made over the past few years are highlighted.
Tumor necrosis factor impairs insulin action on peripheral glucose disposal and hepatic glucose output (1992)

The present study examined whether a prolonged infusion of tumor necrosis factor (TNF) into rats could sustain the increased rate of whole body glucose metabolism observed with short term exposure, and whether TNF produced hepatic or peripheral insulin resistance. Basal glucose metabolism was determined with the use of [3-3H]glucose 18 h after initiating a constant infusion of recombinant human TNF (1 microgram/kg.h). Thereafter, a two-step euglycemic hyperinsulinemic clamp was performed to determine whether TNF impaired insulin action. The overnight infusion of TNF minimally elevated plasma glucose concentrations (17%), but produced large increases in the whole body rate of glucose production and utilization (133%). Under hyperinsulinemic conditions, the glucose infusion rate necessary to maintain euglycemia was 30% lower in TNF-treated rats, indicating an insulin-resistant condition. This resulted from an impaired ability of insulin to both suppress hepatic glucose production and stimulate peripheral glucose utilization in TNF-infused animals. A second series of experiments was performed, using the in vivo tracer [U-14C]2-deoxyglucose technique, to elucidate which tissues were responsible for the TNF-induced increase in basal (no exogenous insulin) glucose disposal and peripheral insulin resistance. Under basal conditions, TNF increased glucose uptake by various muscles (gastrocnemius, heart, and diaphragm) as well as nonmuscle tissues (liver, lung, spleen, gut, skin and fat). Because of their relatively large mass and/or high rate of glucose uptake, the increased uptake by skin (25%), intestine (24%), muscle (23%), and liver (15%) accounted for the majority of the TNF-induced increment in whole body glucose disposal. Under euglycemic hyperinsulinemic conditions, the increment in glucose uptake by muscle and skin (85%) accounted for the majority of the glucose disposal in control rats. However, in TNF-infused animals, hyperinsulinemia failed to increase glucose uptake by skin and blunted the insulin-mediated increase in muscle by 73%. These results suggest that sustained elevations of TNF during chronic therapy and prolonged production of TNF by patients and experimental animals with malignancies or infectious diseases may be an important mechanism for the enhanced glucose flux as well as the insulin resistance seen in these conditions.
Identification of lysosome-associated membrane protein-2 as an activation-dependent platelet surface glycoprotein (1992)

Platelets undergo biochemical and morphologic changes when stimulated that greatly alter their function and contribute to their role in thrombosis and hemostasis. We recently identified and cloned the cDNA for a platelet surface glycoprotein expressed on activated, not resting cells. We found that this protein, lysome-associated membrane protein-1 (LAMP-1), is an integral membrane protein of the lysosome that translocated to the surface membrane when platelets were stimulated by a strong agonist. We now show with immunofluorescence flow cytometry that LAMP-2, a lysosomal membrane protein that shares approximately 30% homology with LAMP-1, is also expressed preferentially on the surface of activated platelets. Equilibrium binding studies with 125I-anti-LAMP-2 IgG showed approximately 1,100 binding sites per thrombin-stimulated platelet and less than 50 per resting platelet. Sucrose gradient ultracentrifugation fractionation of resting platelet sonicates showed that LAMP-2 colocalized with LAMP-1 and with lysosomal enzymes, and not with thrombospondin or serotonin, which are markers of the two other platelet granule compartments, alpha-granules and dense granules. LAMP-2 surface expression was minimal in response to platelet stimulation by weak agonists such as epinephrine and ADP. These data show that LAMP-2, like LAMP-1, translocates from the lysosomal membrane compartment to the surface membrane when platelets are activated. Regulated surface expression of these heavily glycosylated proteins may play a role in the adhesive, prothrombotic phenotype of these cells.
Random multi-recombinant PCR for the construction of combinatorial protein libraries (2001)

Development of a new methodology to create protein libraries, which enable the exploration of global protein space, is an exciting challenge. In this study we have developed random multi-recombinant PCR (RM-PCR), which permits the shuffling of several DNA fragments without homologous sequences. In order to evaluate this methodology, we applied it to create two different combinatorial DNA libraries. For the construction of a 'random shuffling library', RM-PCR was used to shuffle six DNA fragments each encoding 25 amino acids; this affords many different fragment sequences whose every position has an equal probability to encode any of the six blocks. For the construction of the 'alternative splicing library', RM-PCR was used to perform different alternative splicings at the DNA level, which also yields different block sequences. DNA sequencing of the RM-PCR products in both libraries revealed that most of the sequences were quite different, and had a long open reading frame without a frame shift or stop codon. Furthermore, no distinct bias among blocks was observed. Here we describe how to use RM-PCR for the construction of combinatorial DNA libraries, which encode protein libraries that would be suitable for selection experiments in the global protein space.
Modeling middleboxes (2008)

The lack of a concise and standard language to describe diverse middlebox functionality and deployment configurations adversely affects current middlebox deployment, as well as middlebox-related research. To alleviate this problem, we present a simple middlebox model that succinctly describes how different middleboxes process packets and illustrate it by representing four common middleboxes. We set up a pilot online repository of middlebox models and prototyped model inference and validation tools.
Multiwell cell culture plate format with integrated microfluidic perfusion system (2006)

A new cell culture analog has been developed. It is based on the standard multiwell cell culture plate format but it provides perfused three-dimensional cell culture capability. The new capability is achieved by integrating microfluidic valves and pumps into the plate. The system provides a means to conduct high throughput assays for target validation and predictive toxicology in the drug discovery and development process. It can be also used for evaluation of long-term exposure to drugs or environmental agents or as a model to study viral hepatitis, cancer metastasis, and other diseases and pathological conditions.
The Design of Leadlike Combinatorial Libraries (1999)

The optimization of low-potency leads into drugs is often accompanied by an increase in molecular weight (M(r)) and lipophilicity, as a consequence of affinity enhancement. Hits with affinity at µM levels discovered by screening leadlike libraries allow scope for this optimization process, as shown schematically by the distributions of M(r) for a leadlike library (1), oral drugs (2), and a typical combinatorial chemistry library (3). y=percentage with a particular molecular weight.
Myelin Basic Protein in CSF and Blood (1982)

Serum and CSF levels of myelin basic protein (MBP) were measured in 50 patients with encephalitis of various origins and severity. In nearly 50%, the CSF samples were found to display immunoreactivity of MBP. Positivity was found to be correlated with the severity of the clinical signs. More precisely, it corresponded to cases with suspected extensive brain destruction. No relationship could be observed with the cause of disease. Positive tests of sera were infrequent, even from patients whose CSF was rich in MBP. Longitudinal studies performed on 20 patients who were serially investigated during periods ranging from three weeks to 18 months demonstrated that after an attack, MBP liberation into the CSF persists for one to three weeks. The MBP assay should serve as an index for destruction of nervous tissue.
A Randomized, Controlled Trial of Doxycycline and Rifampin for Patients with Alzheimer's Disease (2004)

Therapy with doxycycline and rifampin may have a therapeutic role in patients with mild to moderate AD. The mechanism is unlikely to be due to their effect on C. pneumoniae. More research is needed to investigate these agents.
Effect of Febuxostat on the Progression of Renal Disease in 5/6 Nephrectomy Rats with and without Hyperuricemia (2008)

Fx prevented renal injury in 5/6 Nx rats with and without coexisting hyperuricemia. Because Fx helped to preserve preglomerular vessel morphology, normal glomerular pressure was maintained even in the presence of systemic hypertension.
Sustained cytokine production and immunophenotypic changes in human neuroblastoma cell lines transduced with a human gamma interferon vector. (1995)

The majority of human neuroblastomas express low to undetectable levels of major histocompatibility complex (MHC) class I and II antigens (MHC-I and -II). We studied the effects of gamma interferon (gamma-IFN) transduction on expression of these antigens in six human neuroblastoma cell lines with and without genomic amplification of the N-myc oncogene. All six were stably transduced with an MoMLV-based gamma-IFN retroviral vector (DAh gamma-IFN). G418-resistant cells were assayed for MHC-I, MHC-II, B7-1, and neuroblastoma-associated antigen expression, as well as for gamma-IFN levels in cell culture supernatants. Sustained gamma-IFN production, 2 to > 1000 units/10(6) cells/d, was attained for five of six transduced cell lines and persisted for up to 9 months. This resulted in marked upregulation of MHC-I and MHC-II expression in LA-N-1, LA-N-6, and CHLA-127 cells and moderate upregulation in SK-N-Fi and SK-N-AS cells. One cell line (LA-N-1) had marked induction of MHC-I and MHC-II despite marginal levels of gamma-IFN production. Expression of CD28 ligand B7-1 (as determined by BB1 antibody) remained unchanged in all gamma-IFN-transduced cell lines tested. Expression of several neuroblastoma-associated antigens (NKH1A, 126-4, HSAN 1.2, HNK, 459, and 390) was upregulated in some of the gamma-IFN-transduced cell lines. These results demonstrate that preparation of gamma-IFN expressing neuroblastoma cells for immunotherapeutic purposes is feasible and that gamma-IFN transduction results in phenotypic changes that may improve immunogenicity of human neuroblastoma cells.
1,3-Dioxolanylpurine nucleosides (2R,4R) and (2R,4S) with selective anti-HIV-1 activity in human lymphocytes (1993)

In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV-1 agents, various enantiomers of pure dioxolanylpurine nucleosides were synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 1, which was synthesized in nine steps from 1,6-anhydro-beta-D-mannose, was condensed with 6-chloropurine, 6-chloro-2-fluoropurine, and 2,6-dichloropurine in the presence of TMS triflate. The chloro or fluoro substituents were readily converted into amino, N-methylamino, hydroxy, methoxy, thiol, and methylthio under appropriate reaction conditions. Upon evaluation of these dioxolanes, the guanine derivative 24 exhibited the most potent anti-HIV-1 activity without cytotoxicity up to 100 microM in various cells. The decreasing antiviral activity order of beta-isomers was as follows: guanine > 6-chloro-2-aminopurine > 2-fluoroadenine > or = adenine > or = 2,6-diaminopurine > hypoxanthine > 2-chloroadenine > 6-chloropurine approximately equal to N6-methyladenine approximately equal to 6-mercaptopurine approximately equal to 6-(methylthio)purine.
Advances in Neuropathic Pain (2003)

Chronic neuropathic pain, caused by lesions in the peripheral or central nervous system, comes in many forms. We describe current approaches to the diagnosis and assessment of neuropathic pain and discuss the results of recent research on its pathophysiologic mechanisms. Randomized controlled clinical trials of gabapentin, the 5% lidocaine patch, opioid analgesics, tramadol hydrochloride, and tricyclic antidepressants provide an evidence-based approach to the treatment of neuropathic pain, and specific recommendations are presented for use of these medications. Continued progress in basic and clinical research on the pathophysiologic mechanisms of neuropathic pain may make it possible to predict effective treatments for individual patients by application of a pain mechanism-based approach.
Monoclonal antibody against a unique antigen on human acute promyelocytic leukemia cell line (HL-60). (1982)

An IgM kappa monoclonal antibody (WI-1) reacted against HL-60 cells in indirect immunofluorescence and microcytotoxicity tests. It failed to react against 19 other cell lines representing acute myelogenous leukemia, chronic myelogenous leukemia, lymphocytic leukemias, multiple myeloma, Burkitt's lymphoma, monocytoid cells and virus induced lymphoid cell lines. Normal peripheral blood nucleated cells and bone marrow cells derived from acute granulocytic leukemia, chronic granulocytic leukemia, acute lymphocytic leukemia, and chronic lymphocytic leukemia also failed to react with WI-1. Normal peripheral blood lymphocytes, transferred with mitogens, showed no reaction against the antibody. There was some decrease in the reactivity of the cells, against WI-1, following maturation with dimethyl sulfoxide. However, a large percentage of the cells remained positive after maturation. WI-1 reacted specifically against an antigen on the HL-60 cells which had a molecular weight of about 42,000 dalton. Peripheral blood cells from one patient with acute promyelocytic leukemia failed to react with the antibody. It is possible that acute promyelocytic leukemia is an antigenically heterogeneous disease. A large population of acute promyelocytic leukemia patients needs to be tested to see if the specific antigen on HL-60 cells, detected by WI-1, is demonstrable in other patients with acute promyelocytic leukemia.
Sphingosine-1-Phosphate and Its Analogue FTY720 Diminish Acute Pulmonary Injury in Rats With Acute Necrotizing Pancreatitis (2008)

Sphingosine-1-phosphate and its analogue FTY720 significantly decreased pulmonary inflammation and injury in a rat model of acute lung injury caused by acute necrotizing pancreatitis and may represent a novel therapeutic strategy for the acute necrotizing pancreatitis-associated lung injury.
High throughput flow cytometry (2001)

Background Conventional flow cytometry does not allow the rapid analysis of multiple samples. This has limited its uses in drug discovery, for which the standard for throughput is 100,000 samples per day. Methods We describe a simple method in which commercial peristaltic tubing is connected from a commercial autosampler to a flow cytometer. The samples are delivered via a peristaltic pump from source wells in a multiwell plate. The samples are separated by air bubbles. Results Throughput rates approach the limit of the autosampler (up to 100 wells per minute). Using optimal tubing and flow rates, particles remain within appropriate light scatter and fluorescence gates. The carryover between wells is typically less than 5% without and 1% with a wash step. The volumes of sample delivered are in the microliter scale. The approach has been validated with instruments from three manufacturers. Conclusions Flow cytometry has potential throughput of 100,000 samples or more per day starting with the method described. The method is currently best suited to end-point assays. However, combined with high-speed sorting and single- cell assays, the number of assays could approach 1 billion per day. Cytometry 44:83–90, 2001. © 2001 Wiley-Liss, Inc.
The Effect of an Arenavirus Infection on Liver Morphology and Function (1990)

Patients with severe Lassa fever have high serum levels of liver enzymes. Studies of the histology of the liver have shown only minor alterations, seemingly insufficient to account for death. Pichinde virus is an arenavirus which causes severe illness similar to Lassa fever in strain 13 guinea pigs, but does not cause severe illness in man. This can serve as a relatively safe model for studying the pathology and pathophysiology of fatal arenaviral infection. We used this infection to evaluate the effect of arenavirus on liver morphology and function. When guinea pigs were infected with Pichinde virus, all developed severe disease and died within 14 days of infection. The animals lost large amounts of weight. Higher levels of virus were detected in the liver than in serum. Aspartate aminotransferase and alanine aminotransferase were elevated late in the course of the disease; no elevations were seen in gamma glutamyl transpeptidase or bilirubin. Alkaline phosphatase, initially high in these growing animals, was markedly decreased early in infection. Prothrombin time and activated partial thromboplastin time were increased late in the disease, and decreased levels of Factors VIII and IX were seen relatively early. Fatty metamorphosis, indicating problems in lipid processing, occurred by day 11, but necrosis was minor and occurred late. Pichinde virus infection results in significant alterations in the metabolic and synthetic capacities of the hepatocytes early in infection in the absence of significant necrosis.
Understanding the Effects of Cationic and Anionic Substitutions in Spinel Cathodes of Lithium-Ion Batteries (2013)

With an aim to develop a better understanding of the factors influencing the electrochemical performance of doped spinel cathodes, a series of Li1.1Mn1.8M0.1O4-δFδ and Li1+xMn2-2xMxO4-δFδ (M = Al, Ti, Cr, Fe, Co, and Ni) samples have been investigated systematically. The samples have been made by solid-state reaction followed by a low-temperature fluorination reaction and characterized by X-ray diffraction (XRD), redox titration, scanning electron microscopy (SEM), electrochemical cycling, and differential capacity measurements. Generally, LiF impurity phase begins to form at or above a fluorine content of ∼0.2. The capacity fade decreases with decreasing oxidation state of the dopant Mn+, increasing electronegativity of the dopant M, decreasing bond dissociation energy of M-O, and decreasing Mn dissolution; the capacity fade increases drastically below a Mn valence of ∼3.6+. Additionally, the charge-discharge kinetics worsen with increasing fluorine content.
Ability of a β-casein phosphopeptide to modulate the precipitation of calcium phosphate by forming amorphous dicalcium phosphate nanoclusters (1996)

The ability of casein in the form of colloidal-sized casein micelles to modulate the phase separation of calcium phosphate during milk secretion is adapted to produce nanometre-sized particles of calcium phosphate stabilized by a casein phosphopeptide (nanoclusters). The nanoclusters were prepared from an undersaturated solution of salts and the peptide by raising the pH homogeneously from about 5.5 to 6.7 with urea plus urease. Chemical analysis and IR spectroscopy showed that they comprise an amorphous dicalcium phosophate bound to the phosphopeptide. Multinuclear NMR spectroscopy of the cluster solutions showed that the small ions and free peptide in the solution were in a state of dynamic exchange with the nanoclusters. The peptide is linked to the calcium phosphate through its sequence of phosphorylated residues, but, in a proportion of adsorbed conformational states, the termini retain the conformational freedom of the unbound peptide. The ability of casein to form nanoclusters in milk suggests a more general mechanism for avoiding pathological calcification and regulating calcium flow in tissues and biological fluids exposed to or containing high concentrations of calcium.
Control of Exposure to Mite Allergen and Allergen-Impermeable Bed Covers for Adults with Asthma (2003)

Allergen-impermeable covers, as a single intervention for the avoidance of exposure to dust-mite allergen, seem clinically ineffective in adults with asthma.
Active Control of Wetting Using Applied Electrical Potentials and Self- Assembled Monolayers (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTActive Control of Wetting Using Applied Electrical Potentials and Self- Assembled MonolayersNicholas L. Abbott, Christopher B. Gorman, and George M. WhitesidesCite this: Langmuir 1995, 11, 1, 16–18Publication Date (Print):January 1, 1995Publication History Published online1 May 2002Published inissue 1 January 1995https://pubs.acs.org/doi/10.1021/la00001a005https://doi.org/10.1021/la00001a005research-articleACS PublicationsRequest reuse permissionsArticle Views842Altmetric-Citations121LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Frequency of low level bacteremia in infants from birth to two months of age (1997)

Low level bacteremia was common in our infants' patient population. The culturing of up to 6 ml of blood which represented up to 4.5% of an infant's total blood volume was required for detection of the pathogens.