gebhart/patrepeval huggingface dataset:
Diagnosis and classification of myelodysplastic syndrome: International Working Group on Morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts (2008)

The classification of myelodysplastic syndromes is based on the morphological criteria proposed by the French-American-British (FAB) and World Health Organization (WHO) groups. Accurate enumeration of blast cells, although essential for diagnosis of myelodysplastic syndrome and for assignment to prognostic groups, is often difficult, due to imprecise criteria for the morphological definition of blasts and promyelocytes. An International Working Group on Morphology of Myelodysplastic Syndrome (IWGM-MDS) of hematopathologists and hematologists expert in the field of myelodysplastic syndrome reviewed the morphological features of bone marrows from all subtypes of myelodysplastic syndrome and agreed on a set of recommendations, including recommendations for the definition and enumeration of blast cells and ring sideroblasts. It is recommended that (1) agranular or granular blast cells be defined (replacing the previous type I, II and III blasts), (2) dysplastic promyelocytes be distinguished from cytologically normal promyelocytes and from granular blast cells, (3) sufficient cells be counted to give a precise blast percentage, particularly at thresholds that are important for diagnosis or prognosis and (4) ring sideroblasts be defined as erythroblasts in which there are a minimum of 5 siderotic granules covering at least a third of the nuclear circumference. Clear definitions and a differential count of a sufficient number of cells is likely to improve precision in the diagnosis and classification of myelodysplastic syndrome. Recommendations should be applied in the context of the WHO classification.
Effect of the 3′-leaving group on turnover of cephem antibiotics by a class C β-lactamase (1989)

It has been previously demonstrated for class A beta-lactamases and the DD-peptidase of Streptomyces R61 that the presence of a leaving group at the 3'-position of a cephalosporin can lead to the generation of more-inert acyl-enzyme intermediates than from cephalosporins lacking such a leaving group, and thus to beta-lactamase inhibitors and potentially better antibiotics. In the present work we extend this result to a class C beta-lactamase, that of Enterobacter cloacae P99. The effect is not seen with first-generation cephalosporins, since here deacylation generally seems faster than elimination of the leaving group, but it does clearly appear with cephamycins and third-generation cephalosporins. The structural and/or mechanistic features of the active site giving rise to this phenomenon may thus be common to all serine beta-lactamases and transpeptidases.
Maternal Embryonic Leucine Zipper Kinase/Murine Protein Serine-Threonine Kinase 38 Is a Promising Therapeutic Target for Multiple Cancers (2005)

To identify genes that could serve as targets for novel cancer therapeutics, we used a bioinformatic analysis of microarray data comparing gene expression between normal and tumor-derived primary human tissues. From this approach, we have found that maternal embryonic leucine zipper kinase (Melk), a member of the AMP serine/threonine kinase family, exhibits multiple features consistent with the potential utility of this gene as an anticancer target. An oligonucleotide microarray analysis of multiple human tumor samples and cell lines suggests that Melk expression is frequently elevated in cancer relative to normal tissues, a pattern confirmed by quantitative reverse transcription-PCR and Western blotting of selected primary tumor samples. In situ hybridization localized Melk expression to malignant epithelial cells in 96%, 23%, and 13% of colorectal, lung, and ovarian tissue tumor samples, respectively. Expression of this gene is also elevated in spontaneous tumors derived from the ApcMin and Apc1638N murine models of intestinal tumorigenesis. To begin addressing whether Melk is relevant for tumorigenesis, RNA interference-mediated silencing within human and murine tumor cell lines was done. We show that Melk knockdown decreases proliferation and anchorage-independent growth in vitro as well as tumor growth in a xenograft model. Together, these results suggest that Melk may provide a growth advantage for neoplastic cells and, therefore, inactivation may be therapeutically beneficial.
In vitro study of intracellular IL-1beta production and beta1 integrins expression in stimulated chondrocytes--effect of rhein. (2002)

The purpose of the present study was to investigate the intracellular IL-1beta production and beta1 integrins (alpha4/beta1 and alpha5/beta1) expression on chondrocytes. Chondroytes monolayer (human chondrosarcoma cell line HEM-C55) were incubated for 12, 24 and 48 hours in the presence of Tumor Necrosis Factor-alpha (TNF-alpha, Sigma, France) or recombinant human IL-1alpha (rh-IL1alpha, Becton Dickinson, France). After direct immunolabelling, cells were either analyzed on FACScan flow cytometer (Becton Dickinson, France), or observed under an epi-fluorescence inverted microscope equipped with the CellScan EPR optical scanning acquisition system (IPLab-Scanalytics, USA). We found that the IL-1beta mean fluorescence intensity in flow cytometry and in 3D microscopy was increased in the presence of TNF-alpha or rh-IL-1alpha, and alpha4/beta1 or alpha5/beta1 expression was higher on stimulated cells than on control cells. On the other hand, we have evaluated the in vitro effects of rhein (10(-5) M, Negma, France), an active metabolite of diacerein, on the intracellular IL-1beta and beta1 integrins expressed by stimulated or no-stimulated chondrocytes. The results indicated that rhein leads to a reduction of IL-1beta synthesis whereas a weak decrease of beta1 integrins receptors expression is observed. From this study, it seems that rhein partially reduce cytokine-induced intracellular IL-1beta production, and it has a weak action on alpha4/beta1 or alpha5/beta1 receptors.
Reactive ion-etching-induced damage in silicon using SF6 gas mixtures (1987)

Damage introduced in silicon during reactive-ion etching (RIE) in SI6 gas containing 10 Vol % of H2, He, N2, O2, or Ar has been investigated using Schottky barrier measurements and Rutherford backscattering. RIE was performed at 0.1 Watt cm−2 power density with the radio frequancy (rf) cathode covered with a quartz plate. The annealing effect on damage was studied at various temperatures up to 800 °C in dry N2. The results indicate that the damage has two components namely, a shallow near-surface region with lattice damage and a deep layer containing discrete defect centers which act as donors. The extent of the deep damage layer is the net balance between two competing processes: (a) the etch rate, and (b) the rate of damage migration into silicon. However, the damage has been found to reach a saturation level after RIE for 1 min in all the gas mixtures studied. The results also suggest that RIE in SF6+10% H2 gas mixture causes a deep damage layer which could, however, be annealed at 150 °C aided significantly by the passivation of defect centers by hydrogen permeated during RIE. On the other hand, the damage induced in SF6+10% Ar-etched samples has been found to anneal at 800 °C indicating there by a higher level of lattice damage or amorphization of the near-surface layer of silicon. Therefore, the mass of the bombarding ion significantly affects the nature of the damage layers.
Anergic T Cells Are Metabolically Anergic (2009)

Full T cell activation requires TCR engagement (signal 1) in the context of costimulation (signal 2). Costimulation is required for maximal expression of effector cytokines and prevention of T cell anergy. It has become increasingly clear that another major function of costimulation is to up-regulate the metabolic machinery necessary for T cell function. In this report we demonstrate that anergic T cells are metabolically anergic, in that upon full stimulation (signals 1 plus 2) they fail to up-regulate the machinery necessary to support increased metabolism. These findings suggest that one mechanism responsible for the maintenance of T cell anergy is failure to up-regulate the metabolic machinery. Furthermore, we demonstrate that by blocking leucine, glucose, and energy metabolism, T cell activation is mitigated. Additionally, inhibition of these metabolic pathways during T cell activation leads to anergy in Th1-differentiated cells. Overall, our findings extend the role of T cell metabolism in regulating T cell function.
Optimization of Protein Extraction from Fish Waste using Response Surface Methodology (2009)

The aim of present study was to optimize protein extraction from Fish Waste (FW), sardine (Sardina pilchardus) using enzymatic method. In this study, enzymatic method involved two combinations of enzymes which were alcalase and protamex. Response Surface Methodology (RSM) was used to study the effect of independent variables, namely temperature (35-55°C), rotation speed (100-300 rpm), time (60-1440 min) and enzyme:substrate ratio (0.5-1.5) on protein extraction from FW. From RSM-generated model, the optimum conditions for extraction of protein from FW were identified to be at temperature 35°C in 1429 min reaction time, with rotation speed of 171 rpm and enzyme:substrate ratio of 1.50. At the optimum conditions, predicted protein yield in the extraction process was 80.75 mg mL-1.
Anti-angiogenic therapy of proliferative diabetic retinopathy (2001)

Proliferative diabetic retinopathy (PDR) remains one of the major causes of acquired blindness in developed nations. This is true despite the development of laser treatment, which can prevent blindness in the majority of those who develop this complication. The hallmark of PDR is neovascularisation (NV), abnormal angiogenesis that may ultimately cause severe vitreous cavity bleeding and/or retinal detachment. Pharmacologic therapy aimed at preventing NV, as an adjunct to laser treatment, or as an alternative to laser treatment, would be a welcome addition to the armamentarium. PDR could be prevented by improved metabolic control or by pharmacologically blunting the biochemical consequences of hyperglycaemia (e.g., with aldose reductase inhibitors, inhibitors of non-enzymatic glycation or by protein kinase C (PKC) inhibition). The angiogenesis in PDR could be treated via growth factor (e.g., vascular endothelial growth factor (VEGF), insulin like growth factor-1) blockade, integrin (e.g., alpha-v beta-3) blockade or extracellular matrix alteration (e.g., with steroid compounds), or interference with intracellular signal transduction pathways (e.g., PKC and mitogen activated protein kinase pathway proteins). Numerous potentially useful anti-angiogenic compounds are in development, but two drugs are presently in clinical trials for the treatment of the preproliferative stage of PDR.
Crystal Structure of Bruton's Tyrosine Kinase Domain Suggests a Novel Pathway for Activation and Provides Insights into the Molecular Basis of X-linked Agammaglobulinemia (2001)

Bruton's tyrosine kinase is intimately involved in signal transduction pathways regulating survival, activation, proliferation, and differentiation of B lineage lymphoid cells. Mutations in the human btk gene are the cause of X-linked agammaglobulinemia, a male immune deficiency disorder characterized by a lack of mature, immunoglobulin-producing B lymphocytes. We have determined the x-ray crystal structure of the Bruton's tyrosine kinase kinase domain in its unphosphorylated state to a 2.1 A resolution. A comparison with the structures of other tyrosine kinases and a possible mechanism of activation unique to Bruton's tyrosine kinase are provided.
Conformational, thermodynamic, and stability properties of Manduca sexta apolipophorin III. (1993)

Apolipophorin III (apoLp-III) is a major protein in hemolymph of adult Manduca sexta. Although it normally exists in a lipid-free state, during sustained flight, apoLp-III functions as an apolipoprotein, reversibly associating with the surface of lipoprotein particles. In an effort to gain a fuller understanding of this dual existence, we have investigated its solution properties using spectroscopic methods. The UV absorption spectrum of apoLp-III is distinctive owing to the absence of tryptophan and the presence of a single tyrosine residue. Circular dichroism experiments revealed an enhancement of apoLp-III alpha-helical content when spectra were obtained in 50% trifluoroethanol versus aqueous buffer. The helical content in buffer was unaffected by protein concentration, suggesting that apoLp-III exists in solution as a monomeric species. At pH values > 10 and < 4, there was a marked loss of helical content. Increasing the temperature of apoLp-III solutions also caused a loss of secondary structure, with a temperature-induced denaturation midpoint of 52 degrees C. Upon recooling of heat-denatured apoLp-III, approximately 95% of the secondary structure was restored. In guanidine HCl denaturation studies monitored by CD, a 50% transition midpoint of 0.355 M was determined, corresponding to a delta GDH2O of 1.29 kcal/mol. Fluorescence studies indicated that guanidine HCl induced an enhancement of tyrosine fluorescence emission at 300 nm when excited at 277 nm. In native apoLp-III, we propose that tyrosine fluorescence is quenched to a large extent due to a hydrophobic stacking interaction of its side chain with that of a neighboring phenylalanine residue. delta GDH2O was determined from the fluorescence data to be 2.1 kcal/mol, with a transition midpoint occurring at 0.25 M guanidine HCl. The lower concentration of guanidine HCl required to induce half-maximal tyrosine fluorescence enhancement versus the transition midpoint detected by CD may be a reflection of the fact that this residue is located near the COOH-terminal end of the protein and as such may be more susceptible to denaturation. The results presented indicate that apoLp-III assumes a relatively labile conformation in solution that appears to be partially stabilized by side chain charge-charge interactions within predicted alpha-helical segments.
Strand Invasion of Mixed-Sequence B-DNA by Acridine-Linked, γ-Peptide Nucleic Acid (γ-PNA) (2007)

Peptide nucleic acid (PNA) is a synthetic mimic of DNA and RNA that can recognize double-stranded B-DNA through direct Watson-Crick base-pairing. Although promising, PNA recognition is presently limited to mostly purine- and pyrimidine-rich targets, because mixed-sequence PNA, in general, does not have sufficient binding free energy to invade B-DNA. In this Article, we show that conformationally preorganized gamma-peptide nucleic acid (gamma-PNA) containing an acridine moiety covalently linked at the C-terminus can invade mixed-sequence B-DNA in a sequence-specific manner. Recognition occurs through direct Watson-Crick base-pairing. This finding is significant because it demonstrates that the same principles that guide the recognition of single-stranded DNA and RNA can also be applied to double-stranded B-DNA.
Defining Human Embryo Phenotypes by Cohort-Specific Prognostic Factors (2008)

Our findings support defining human embryo phenotypes by non-redundant, prognostic variables that are specific to sibling embryos in a cohort.
Expression patterns of CD44 and CD44 splice variants in patients with rheumatoid arthritis. (2012)

Expression of CD44 splice variants is generally increased in the synovial lining of RA patients when compared to OA. The inverse association of CD44v3 expression on monocytes with the development of erosive disease and the functional impacts of CD44v4 blockade in RA-FLS suggests a pathogenetic role of this splice variants which needs to be further investigated.
Effect of Electrode Potential on Electrode-Reducing Microbiota (2006)

The benthic microbial fuel cell (BMFC) generates power by coupling oxidation of fuels naturally residing in marine sediments with reduction of oxygen in overlying waters. A central feature of BMFCs is spontaneous colonization of the anode by mineral-reducing microorganisms indigenous to marine sediments that catalyze the power-generating anodic reactions. Described here is a preliminary investigation of how the anode potential affects this feature. Different oxidative potentials were applied to a set of anodes under conditions known to promote anode enrichment of acetate oxidizing/mineral reducing microorganisms. In-situ analysis of current, acetate consumption, and reducing ability of the anode colonies suggest thatthe microorganisms conserve a significant portion (as much as 95%) of potential energy liberated from oxidation of acetate and reduction of the anode for their own metabolic benefit. The implication of this result with respect to BMFCs, and other MFCs utilizing electrode-reducing microbial catalysts, is that although the microorganisms enable long-term stability of such fuel cells, they may significantly impact efficiency of power output per equivalent of fuel consumed.
Extraction and Analysis of Diagnostically Useful Proteins from Formalin-fixed, Paraffin-embedded Tissue Sections (1998)

We describe and discuss a method of protein extraction for Western blot analysis from formalin-fixed, paraffin-embedded tissue sections. From 5-mm2 50-micron-thick tissue sections, an abundance of proteins could be extracted by incubating the sections in lysis buffer containing 2% sodium dodecyl sulfate (SDS) at 100C for 20 min followed by incubation at 60C for 2 hr. Extracts yielded discernible protein bands ranging from 10 kD to 120 kD as identified by SDS-polyacrylamide gel electrophoresis (PAGE). Western blot analysis successfully detected membrane-bound protein such as E-cadherin, cytosolic protein such as beta-catenin, and nuclear proteins including proliferating cell nuclear antigen (PCNA), mutant-type p53, cyclin D1, cyclin E, and cyclin-dependent kinases (CDKs). With this technique, we could examine cyclin D1 and CDK2 expression in small adenomas compared with cancer tissues and normal mucosa. The simple method of protein extraction described here should make it possible to use large-scale archives of formalin-fixed, paraffin-embedded samples for Western blot analysis, and its application could lead to detailed analysis of protein expression. This new technique should yield valuable information for molecular biology.
Cytotoxic and DNA‐Damaging Effects of Diterpenoid Quinones from the Roots of Salvia officinalis L. on Colonic and Hepatic Human Cells Cultured in vitro (2004)

Three diterpenoid quinones (royleanone- SAR 3, horminone- SAR 26, and acetyl horminone- SAR 43) isolated from the roots of Salvia officinalis L. were tested for their cytotoxic and DNA-damaging activity in human colon carcinoma cells Caco-2 and human hepatoma cells HepG2 cultured in vitro. Cytotoxicity was measured by the trypan blue exclusion technique and induction of apoptosis was evaluated by flow immunofluorocytometry after 30-300 min. exposure of HepG2 and Caco-2 cells to diterpenoid quinones and following 24 hr post-incubation in the culture medium. Induction of DNA breaks was measured after 60 min. exposure of cells to different concentrations of the compounds studied by the alkaline elution of DNA and by the Comet assay. Though all the quinones tested decreased the viability of the cells studied proportionally to the concentration and to the time of treatment (cytotoxicity= 30-60%), the increased level of apoptotic nuclei comparable to the level of apoptotic nuclei induced by a topoisomerase I inhibitor was proved only in HepG2 cells treated with 1x10(-4) mol/l SAR 26 or SAR 43. Either no or marginal increase of the level of apoptotic nuclei was observed in SAR 3-treated HepG2 cells and in SAR 3-, SAR 26- or SAR 43-treated Caco-2 cells. All compounds tested induced creation of DNA strand breaks in both cell types at concentrations >1x10(-7)-1x10(-6) mol/l. The occurrence of DNA strand breaks at different pH values as well as the kinetics of DNA breaks rejoining were evaluated only in colonic cells Caco-2. The Comet assay processed in parallel at pH 13.0 and pH 12.1 showed that strand breaks detected in SARs-treated colonic Caco-2 cells originated from alkali-labile sites, as induced DNA lesions were converted to DNA strand breaks only under strong alkaline conditions. The kinetics of DNA rejoining revealed that SARs-induced DNA breaks were repaired very slowly.
Safe Negative Margin Width in Breast Conservative Therapy: Results from a Population with a High Percentage of Negative Prognostic Factors (2014)

A negative margin width of 2 mm might represent an adequate negative margin width in the Pakistani population undergoing breast conservative therapy.
Butyric acid-based feed additives help protect broiler chickens from Salmonella Enteritidis infection (2009)

Sodium butyrate is a sodium salt of a volatile short-chain fatty acid (butyric acid) used to prevent Salmonella Enteritidis infection in birds. Three groups of fifty 1-d-old broilers each were fed the following diets: T0 = standard broiler diet (control); T1 = standard broiler diet supplemented with 0.92 g/kg of an additive with free sodium butyrate (Gustor XXI B92); and T2 = standard broiler diet supplemented with 0.92 g/kg of an additive with sodium butyrate partially protected with vegetable fats (Gustor XXI BP70). Twenty percent of the birds were orally infected with Salmonella Enteritidis at d 5 posthatching and fecal Salmonella shedding was assessed at d 6, 9, 13, 20, 27, 34, and 41 of the trial. At d 42, all birds were slaughtered and 20 of them dissected: crop, cecum, liver, and spleen were sampled for bacteriological analyses. Both butyrate-based additives showed a significant reduction (P < 0.05) of Salmonella Enteritidis infection in birds from d 27 onward. However, the partially protected butyrate additive was more effective at the late phase of infection. Partially protected butyrate treatment successfully decreased infection not only in the crop and cecum but also in the liver. There were no differences in the spleen. These results suggest that sodium butyrate partially protected with vegetable fats offers a unique balance of free and protected active substances effective all along the gastrointestinal tract because it is slowly released during digestion.
Engineering Intracellular CMP-Sialic Acid Metabolism into Insect Cells and Methods to Enhance Its Generation (2005)

Previous studies have reported that insect cell lines lack the capacity to generate endogenously the nucleotide sugar, CMP-Neu5Ac, required for sialylation of glycoconjugates. In this study, the biosynthesis of this activated form of sialic acid completely from endogenous metabolites is demonstrated for the first time in insect cells by expressing the mammalian genes required for the multistep conversion of endogenous UDP-GlcNAc to CMP-Neu5Ac. The genes for UDP-GlcNAc-2-epimerase/ManNAc kinase (EK), sialic acid 9-phosphate synthase (SAS), and CMP-sialic acid synthetase (CSAS) were coexpressed in insect cells using baculovirus expression vectors, but the CMP-Neu5Ac and precursor Neu5Ac levels synthesized were found to be lower than those achieved with ManNAc supplementation due to feedback inhibition of the EK enzyme by CMP-Neu5Ac. When sialuria-like mutant EK genes, in which the site for feedback regulation has been mutated, were used, CMP-Neu5Ac was synthesized at levels more than 4 times higher than that achieved with the wild-type EK and 2.5 times higher than that achieved with ManNAc feeding. Addition of N-acetylglucosamine (GlcNAc), a precursor for UDP-GlcNAc, to the media increased the levels of CMP-Neu5Ac even more to a level 7.5 times higher than that achieved with ManNAc supplementation, creating a bottleneck in the conversion of Neu5Ac to CMP-Neu5Ac at higher levels of UDP-GlcNAc. The present study provides a useful biochemical strategy to synthesize and enhance the levels of the sialylation donor molecule, CMP-Neu5Ac, a critical limiting substrate for the generation of complex glycoproteins in insect cells and other cell culture systems.
Crystal structure of (5-bromo-2-pyridyl)ferrocene, C15H12BrFeN (2012)

C 15 H 12 BrFeN, orthorhombic, Pbca (no. 61)