gebhart/patrepeval huggingface dataset:
Analysis of the glutathione S-transferase (GST) gene family (2004)

The glutathione S-transferase (GST) gene family encodes genes that are critical for certain life processes, as well as for detoxication and toxification mechanisms, via conjugation of reduced glutathione (GSH) with numerous substrates such as pharmaceuticals and environmental pollutants. The GST genes are upregulated in response to oxidative stress and are inexplicably overexpressed in many tumours, leading to problems during cancer chemotherapy. An analysis of the GST gene family in the Human Genome Organization-sponsored Human Gene Nomenclature Committee database showed 21 putatively functional genes. Upon closer examination, however, GST-kappa 1 (GSTK1), prostaglandin E synthase (PTGES) and three microsomal GSTs (MGST1, MGST2, MGST3) were determined as encoding membrane-bound enzymes having GST-like activity, but these genes are not evolutionarily related to the GST gene family. It is concluded that the complete GST gene family comprises 16 genes in six subfamilies--alpha (GSTA), mu (GSTM), omega (GSTO), pi (GSTP), theta (GSTT) and zeta (GSTZ).
Emergence and Evolution of Enfuvirtide Resistance following Long-Term Therapy Involves Heptad Repeat 2 Mutations within gp41 (2005)

The objective of this study was to track the evolution of sequence changes in both the heptad region 1 (HR1) and HR2 domains of gp41 associated with resistance to enfuvirtide (ENF) in a patient cohort receiving long-term ENF treatment. We studied 17 highly antiretroviral agent-experienced patients receiving long-term ENF treatment with virological rebound or a lack of suppression. Sixty-two samples obtained after between 5 and 107 weeks of ENF therapy were analyzed. Baseline samples from 15 of these 17 patients were available for analysis. Viruses from five samples from four patients were also sequenced after the cessation of ENF therapy. Drug susceptibilities were assessed by a pseudotype virus reporter assay. We identified HR1 and HR2 sequence changes over time in relation to the baseline sequences. Mutations in HR1 (amino acids 36 to 45) were noted in all cases, including previously unreported changes N42Q/H and N43Q. In addition to a range of HR2 sequence changes at polymorphic sites, isolates from 6 of 17 (35%) patients developed an S138A substitution in the HR2 domain at least 8 weeks after the start of ENF treatment and also subsequent to the first emergence of HR1 mutations. In most, but not all, cases the S138A mutation accompanied HR1 mutations at position 43. Molecular modeling demonstrates the close proximity of S138A with amino acids 40 and 45 in HR1. Of note, isolates in samples available from four patients demonstrated the loss of both the HR1 and the S138A HR2 mutations following the cessation of therapy. We show that the S138A HR2 mutation increased the level of resistance by approximately threefold over that conferred by the HR1 mutation N43D. Continual evolution of HR1 in the domain from amino acids 36 to 45 was observed during long-term ENF therapy. We have identified, for the first time, an ENF resistance-associated HR2 mutation, S138A, which appeared in isolates from 6 of 17 patients with virological failure and demonstrated its potential to contribute to drug resistance. We propose that this represents a possible secondary and/or compensatory mutation, particularly when it coexists with mutations at position 43 in HR-1.
The Saccharomyces cerevisiae Cell Cycle (1981)

INTRODUCTION The cell cycle is the process of vegetative (asexual) cellular reproduction; in a normal cell cycle, one cell gives rise to two cells that are genetically identical to the original cell. Questions about the cell cycle can be conveniently divided into two categories. First, one can ask how a cell carries out a cell cycle, once it has undertaken to do so. Into this category fall questions about the morphological and biochemical aspects of cell-cycle events and about the mechanisms that ensure their temporal and functional coordination. Second, one can ask what determines when a cell will undertake a cell cycle, or how the overall control of cell proliferation is achieved. Into this category fall questions about the coordination of successive cell cycles, the coordination of growth with division, the coordination of cell proliferation with the availability of essential nutrients, and the selection of developmental alternatives. In the text that follows, we consider these two categories of questions in turn. Our bibliography is intended more as a guide to the literature than as a historically accurate record of the development of the field; we apologize to the earlier workers whose contributions thus get less explicit credit than they deserve. HOW DOES A CELL CARRY OUT A CELL CYCLE? As has often been noted, successful completion of a cell cycle requires a cell to integrate the processes that duplicate the cellular material with the processes that partition the duplicated material into two viable daughter cells. Another useful formulation of the...
EFFECT OF FREQUENCY, CIRCUIT ANALYSIS & INSTRUMENT ON EXTRACELLULAR & TOTAL BODY RESISTANCE. (1995)

Gilbert, J. H.1; Suire, S. S.1; Gretebeck, R.2; Wong, W. W.3; Siconolfi, S. F.4 Author Information
Highly-integrated lab-on-chip system for point-of-care multiparameter analysis (2011)

A novel innovative approach towards a marketable lab-on-chip system for point-of-care in vitro diagnostics is reported. In a consortium of seven Fraunhofer Institutes a lab-on-chip system called "Fraunhofer ivD-platform" has been established which opens up the possibility for an on-site analysis at low costs. The system features a high degree of modularity and integration. Modularity allows the adaption of common and established assay types of various formats. Integration lets the system move from the laboratory to the point-of-need. By making use of the microarray format the lab-on-chip system also addresses new trends in biomedicine. Research topics such as personalized medicine or companion diagnostics show that multiparameter analyses are an added value for diagnostics, therapy as well as therapy control. These goals are addressed with a low-cost and self-contained cartridge, since reagents, microfluidic actuators and various sensors are integrated within the cartridge. In combination with a fully automated instrumentation (read-out and processing unit) a diagnostic assay can be performed in about 15 min. Via a user-friendly interface the read-out unit itself performs the assay protocol, data acquisition and data analysis. So far, example assays for nucleic acids (detection of different pathogens) and protein markers (such as CRP and PSA) have been established using an electrochemical read-out based on redoxcycling or an optical read-out based on total internal reflectance fluorescence (TIRF). It could be shown that the assay performance within the cartridge is similar to that found for the same assay in a microtiter plate. Furthermore, recent developments are the integration of sample preparation and polymerase chain reaction (PCR) on-chip. Hence, the instrument is capable of providing heating-and-cooling cycles necessary for DNA-amplification. In addition to scientific aspects also the production of such a lab-on-chip system was part of the development since this heavily affects the success of a later market launch. In summary, the Fraunhofer ivD-platform covers the whole value chain ranging from microfluidics, material and polymer sciences, assay and sensor development to the production and assembly design. In this consortium the gap between diagnostic needs and available technologies can be closed.
Antibacterial and pharmacokinetic properties of M14659, a new injectable semisynthetic cephalosporin. (1988)

In vitro and in vivo antibacterial activities and pharmacokinetics of M14659 were investigated. In vitro activity of M14659 was superior to that of ceftazidime against Staphylococcus aureus. Against Gram-negative bacteria except Pseudomonas aeruginosa, its activity was almost equal to that of ceftazidime. M14659 was more active against P. aeruginosa including multi-drug resistant strains than cefsulodin, cefoperazone or ceftazidime. Affinities of M14659 for penicillin-binding proteins (PBPs) of Escherichia coli and P. aeruginosa were 2 to 14 times higher for PBP-1A and PBP-1B than found for ceftazidime, and almost the same for PBP-3. In vivo activity of M14659 against S. aureus was superior to that of cefamandole, cefotaxime or ceftazidime. Against Gram-negative bacteria including P. aeruginosa, M14659 was 2 to 220 times more active than cefotaxime or ceftazidime. Plasma half-life of M14659 in mice was about 3 times longer than that of ceftazidime. M14659 administered intravenously to mice was mainly excreted in urine without metabolism, and its recovery rate was almost equal to that of ceftazidime.
A comparison of the optical projection lithography simulators in SAMPLE and PROLITH (1992)

This paper documents important algorithmic details not available in the open literature, and illustrates differences and similarities between the SAMPLE and PROLITH programs using representative lithography systems as examples. Numerical comparisons demonstrate that the aerial images calculated by SAMPLE and PROLITH are in generally good agreement. At high numerical resolution, the programs provide the same qualitative lithographic information, including latent images and edge profile results; however, significant degradation occurs at lower restorations. Adequate results are obtained using a vertical resolution smaller than one-twentieth of the theoretical standing-wave wavelength. Significant disagreement is found in the output of the post-exposure bake algorithms where SAMPLE predicts much lower standing-wave amplitude attenuation effects.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Meat Freshness: Peroxynitrite’s Oxidative Role, Its Natural Scavengers, and New Measuring Tools (2014)

Typically, about $1 billion/year is lost when red meat loses freshness on the shelf. Consumer purchasing decisions depend on meat color and flavor, which are strongly influenced by complex nitro-oxidative events within meat muscle tissue. One goal of this chapter is to explain the loss in meat freshness linked to the action of peroxynitrite anion ONOO–, a strong nitro-oxidative agent. The toxicity of abnormally high ONOO– levels in vivo has been proven, and ONOO– is also suspected of accelerating meat spoilage by two principal mechanisms: (1) oxidation of iron atoms in heme-containing globin proteins, leading to a color change from red to brown, and (2) peroxidation of unsaturated lipids, leading to flavor degradation. A second goal is to review electrochemical quantification methods for ONOO– and its oxidative effects on biologically relevant molecules, including unsaturated phospholipids within biological membranes and heme-containing molecules. A third goal is to examine the natural polyphenols that protect against peroxynitrite–induced oxidative damage. The final goal is to assess research advances and remaining research challenges related to ONOO–induced oxidative processes that reduce meat’s shelf life.
Determination of the metal ion dependence and substrate specificity of a hydratase involved in the degradation pathway of biphenyl/chlorobiphenyl (2005)

BphH is a divalent metal ion-dependent hydratase that catalyzes the formation of 2-keto-4-hydroxypentanoate from 2-hydroxypent-2,4-dienoate (HPDA). This reaction lies on the catabolic pathway of numerous aromatics, including the significant environmental pollutant, polychlorinated biphenyls (PCBs). BphH from the PCB degrading bacterium, Burkholderia xenoverans LB400, was overexpressed and purified to homogeneity. Atomic absorption spectroscopy and Scatchard analysis reveal that only one divalent metal ion is bound to each enzyme subunit. The enzyme exhibits the highest activity when Mg2+ was used as cofactor. Other divalent cations activate the enzyme in the following order of effectiveness: Mg2+ > Mn2+ > Co2+ > Zn2+ > Ca2+. This differs from the metal activation profile of the homologous hydratase, MhpD. UV-visible spectroscopy of the Co2+-BphH complex indicates that the divalent metal ion is hexa-coordinated in the enzyme. The nature of the metal ion affected only the kcat and not the Km values in the BphH hydration of HPDA, suggesting that cation has a catalytic rather than just a substrate binding role. BphH is able to transform alternative substrates substituted with methyl- and chlorine groups at the 5-position of HPDA. The specificity constants (kcat/Km) for 5-methyl and 5-chloro substrates are, however, lowered by eight- and 67-fold compared with the unsubstituted substrate. Significantly, kcat for the chloro-substituted substrate is eightfold lower compared with the methyl-substituted substrate, showing that electron withdrawing substituent at the 5-position of the substrate has a negative influence on enzyme catalysis.
The contribution of cross‐links to protein stability: A normal mode analysis of the configurational entropy of the native state (1993)

Abstract The vibrational entropy of native BPTI, with three disulfide bonds, was determined by use of normal mode calculations and compared with that of folded variants having either one less disulfide bond or lacking a peptide bond at the trypsin‐reactive site. Favorable contributions to the free energy of 2.5–5.1 kcal/mol at 300 K were calculated for the reduction of disulfide bonds in the folded state, whereas no favorable contribution was found for the hydrolysis of the peptide bond cleaved by trypsin. This is on the order of the effect of disulfides in the unfolded state. The implications of these results for the stabilization of a folded protein by the introduction of crosslinks are discussed. © 1993 Wiley‐Liss, Inc.
Polymerization reactions in porous coordination polymers (2009)

Recent developments in polymerizations within the nanochannels of porous coordination polymers (PCPs) are covered in this tutorial review. The characteristic features of PCPs are regular structures, controllable channel sizes and shapes, a designable surface functionality, and flexible frameworks, which can be utilized for precision polymer synthesis and specific polymer confinement. This review discusses promising approaches to multiple controls of polymer structures, analysis systems for low-dimensional polymer assemblies and the construction of PCP-polymer nanohybrids, which are strong enticements to researchers in the areas of inorganic, materials and polymer chemistry.
Alcohol/Cholecystokinin-evoked Pancreatic Acinar Basolateral Exocytosis Is Mediated by Protein Kinase Cα Phosphorylation of Munc18c (2007)

The pancreatic acinus is the functional unit of the exocrine pancreas whose role is to secrete zymogens into the gut lumen for food digestion via apical exocytosis. We previously reported that supramaximal CCK induced apical blockade and redirected exocytosis to ectopic sites on the basolateral plasma membrane (BPM) of this polarized cell, leading to pancreatitis. Basolateral exocytosis was mediated by protein kinase C phosphorylation of BPM Munc18c, causing its displacement into the cytosol and activation of BPM-bound Syntaxin-4 to form a SNARE complex. To mimic the conditions of alcoholic pancreatitis, we now examined whether 20 mm alcohol followed by submaximal CCK might mimic supramaximal CCK in inducing these pathologic exocytotic events. We show that a non-secretory but clinically relevant alcohol concentration (20 mm) inhibited submaximal CCK (50 pM)-stimulated amylase secretion by blocking apical exocytosis and redirecting exocytosis to less efficient BPM, indeed mimicking supramaximal CCK (10 nM) stimulation. We further demonstrate that basolateral exocytosis caused by both stimulation protocols is mediated by PKC alpha-induced phosphorylation of Munc18c: 1) PKC alpha is activated, which binds and induces phosphorylation of PM-Munc18c at a Thr site, and these events can be inhibited by PKC alpha blockade; 2) PKC alpha inhibition blocks Munc18c displacement from the BPM; 3) PKC alpha inhibition prevents basolateral exocytosis but does not rescue apical exocytosis. We conclude that 20 mm alcohol/submaximal CCK as well supramaximal CCK stimulation can trigger pathologic basolateral exocytosis in pancreatic acinar cells via PKC alpha-mediated activation of Munc18c, which enables Syntaxin-4 to become receptive in forming a SNARE complex in the BPM; and we further postulate this to be an underlying mechanism contributing to alcoholic pancreatitis.
Cloning of aldB, which encodes alpha-acetolactate decarboxylase, an exoenzyme from Bacillus brevis (1990)

A gene for alpha-acetolactate decarboxylase (ALDC) was cloned from Bacillus brevis in Escherichia coli and in Bacillus subtilis. The 1.3-kilobase-pair nucleotide sequence of the gene, aldB, encoding ALDC and its flanking regions was determined. An open reading frame of 285 amino acids included a typical N-terminal signal peptide of 24 or 27 amino acids. A B. subtilis strain harboring the aldB gene on a recombinant plasmid processed and secreted ALDC. In contrast, a similar enzyme from Enterobacter aerogenes is intracellular.
EFFECTS OF QUERCETIN ON CELL MORPHOLOGY AND EXPRESSION OF PML mRNA AND PROTEIN OF NB4 AND HL-60 CELLS (2001)

Objective To investigate the effects of quercetin on cell morphology, expression of promye-locytic leukemia (PML) mRNA and PML protein localization of NB4, HL-60 cells. Methods Cells mor-phology assayed by Wright' s stain, fluorescence stain, and PML mRNA expression by RT-PCR, PML protein localization by immuno-fluorescence. Results The typical apoptosis was found in NB4 and HL-60 cells after treatment with quercetin. Immuno-fluorescence analysis showed after treatment with quercetin, the fusion pro-tein disappeared in NB4 cells, PML protein relocated, then degraded, and that also seen in HL-60 cells. The expression of PML mRNA is not changed in quercetin-treated cells. Conclusion PML play the role of apop-tosis inducer in leukemia cells at the translational level, quercetin can inhibit the proliferation of leukemia cells, and induce NB4, HL-60 cells apoptosis.
Cascade object detection with deformable part models (2010)

We describe a general method for building cascade classifiers from part-based deformable models such as pictorial structures. We focus primarily on the case of star-structured models and show how a simple algorithm based on partial hypothesis pruning can speed up object detection by more than one order of magnitude without sacrificing detection accuracy. In our algorithm, partial hypotheses are pruned with a sequence of thresholds. In analogy to probably approximately correct (PAC) learning, we introduce the notion of probably approximately admissible (PAA) thresholds. Such thresholds provide theoretical guarantees on the performance of the cascade method and can be computed from a small sample of positive examples. Finally, we outline a cascade detection algorithm for a general class of models defined by a grammar formalism. This class includes not only tree-structured pictorial structures but also richer models that can represent each part recursively as a mixture of other parts.
An Essential Role for Resident Fibroblasts in Experimental Lung Fibrosis Is Defined by Lineage-Specific Deletion of High-Affinity Type II Transforming Growth Factor β Receptor (2010)

Intact TGFβ signaling in resident pulmonary fibroblasts is essential for pulmonary fibrosis to develop. Our data support a key regulatory role of these cells in determining fibrocyte recruitment and myofibroblast differentiation.
Structural Determinants for High-Affinity Binding of Insulin-Like Growth Factor II to Insulin Receptor (IR)-A, the Exon 11 Minus Isoform of the IR (2004)

Abstract The insulin receptor (IR) lacking the alternatively spliced exon 11 (IR-A) is preferentially expressed in fetal and cancer cells. The IR-A has been identified as a high-affinity receptor for insulin and IGF-II but not IGF-I, which it binds with substantially lower affinity. Several cancer cell types that express the IR-A also overexpress IGF-II, suggesting a possible autocrine proliferative loop. To determine the regions of IGF-I and IGF-II responsible for this differential affinity, chimeras were made where the C and D domains were exchanged between IGF-I and IGF-II either singly or together. The abilities of these chimeras to bind to, and activate, the IR-A were investigated. We also investigated the ability of these chimeras to bind and activate the IR exon 11+ isoform (IR-B) and as a positive control, the IGF-I receptor (IGF-1R). We show that the C domain and, to a lesser extent, the D domains represent the principal determinants of the binding differences between IGF-I and IGF-II to IR-A. The C and D domains of IGF-II promote higher affinity binding to the IR-A than the equivalent domains of IGF-I, resulting in an affinity close to that of insulin for the IR-A. The C and D domains also regulate the IR-B binding specificity of the IGFs in a similar manner, although the level of binding for all IGF ligands to IR-B is lower than to IR-A. In contrast, the C and D domains of IGF-I allow higher affinity binding to the IGF-1R than the analogous domains of IGF-II. Activation of IGF-1R by the chimeras reflected their binding affinities whereas the phosphorylation of the two IR isoforms was more complex.
A human ferritin iron oxide nano‐composite magnetic resonance contrast agent (2008)

Macrophages play important roles in the immunological defense system, but at the same time they are involved in inflammatory diseases such as atherosclerosis. Therefore, imaging macrophages is critical to assessing the status of these diseases. Toward this goal, a recombinant human H chain ferritin (rHFn)-iron oxide nano composite has been investigated as an MRI contrast agent for labeling macrophages. Iron oxide nanoparticles in the form of magnetite (or maghemite) with narrow size distribution were synthesized in the interior cavity of rHFn. The composite material exhibited the R(2) relaxivity comparable to known iron oxide MRI contrast agents. Furthermore, the mineralized protein cages are readily taken up by macrophages in vitro and provide significant T2* signal loss of the labeled cells. These results encourage further investigation into the development of the rHFn-iron oxide contrast agent to assess inflammatory disease status such as macrophage-rich atherosclerotic plaques in vivo.
Endoscopic complications. Results of the 1974 American Society for Gastrointestinal Endoscopy Survey (1976)

Esophagogastroduodenoscopy (211,410 examinations) had a complication rate of 1.3/1,000 cases. Duodenoscopy with cannulation was performed 3,884 times and had a complication rate of 21.6/1,000 examinations. Diagnostic coloscopy (25,298 examinations) had a complication rate of 3.4/1,000. Polypectomies during coloscopy (6,124 cases) had a complication rate of 23.3/1,000 cases. Esophageal dilations (13,139 cases) had a complication rate of 4.25 with mercury bougies, and in 9,431 cases metal olives produced a complication rate of 6.1/1,000 treatments. Dilation for achalasia in 1,224 patients produced a complication rate of 18.4/1,000 procedures. Peritoneoscopy (4,404 examinations) produced a complication rate of 5.4/1,000 patients. The value of these diagnostic and therapeutic procedures is now well established but must be weighed against a potential risk of complications.