gebhart/patrepeval huggingface dataset:
Treatment of Refractory or RecurrentClostridium difficileInfection (2012)

Measuring gastric antral emptying time with 3-D ultrasonography may be useful but require further validation studies and advance in technology.
SCHIZOPHRENIA AND POLYMORPHIC CAG REPEATS ARRAY OF CALCIUM-ACTIVATED POTASSIUM CHANNEL (KCNN3) GENE IN SERBIAN POPULATION (2006)

KCNN3 might be a candidate gene for schizophrenia. The KCNN3 cDNA sequence contains two stretches of CAG trinucleotide repeats encoding two separate polyglutamine segments near the N-terminus of this channel protein. The second CAG repeat is highly polymorphic in the Caucasian population from both Europe and United States. The authors carried out a study to compare the allelic frequency distribution of the CAG repeat in KCNN3 gene in 55 Serbian schizophrenic patients and 46 controls. The data indicate a significant association between longer CAG repeats in second polymorphic KCNN3 region and schizophrenia in the Serbian population.
Insulin Action, Regional Fat, and Myocyte Lipid: Altered Relationships with Increased Adiposity (2003)

Interrelationships among body fat depots, myocyte triglyceride, serum lipids, and insulin action are generally absent with increased adiposity. However, visceral abdominal fat, which corresponds less closely to total adiposity, remains an important predictor of insulin resistance in men with both normal and increased adiposity.
Studies on Antibiotics and Related Substances. XXIX. Syntheses of 2-Acetamido-5-oxo-6-heptenoic Acid and 2-Acetamido-4-oxo-5-hexenoic Acid (1967)

Abstract In continuing our study of the relationship between structural and antitumor activity, α-acetylamino acids containing a terminal methyleneketo group (namely, 2-acetamido-5-oxo-6-heptenoic acid, and 2-acetamido-4-oxo-5-hexenoic acid) and related derivatives have been synthesized. Their structures were confirmed by a study of their chemical reactions and their ultraviolet and infrared absorption spectra. It has been found that methyl esters of the α-acetylamino acids showed significant antitumor activity, whereas the free N-acetyl acid failed to show such activity.
Degrees of Transaction Isolation in SQL*Cache: A Predicate-based Client-side Caching System (1996)

A caching scheme that uses query predicates to cache data on the client-side in a client-server relational database system was presented in [15]. The client-side cache (henceforth referred to as a SQL*Cache), loads query results dynamically in the course of transaction execution, and formulates a cache description based on the query predicates. SQL*Cache is associative in nature, in that it supports content-based reasoning and local execution of SQL queries on the cached data, thereby attempting to reduce query response times and increase server throughput. Local caching involves cache consistency maintenance and complicates transaction concurrency control | in this paper, we examine serializability questions that arise in such a system. We rst analyze the issues in supporting di erent (0/1/2/3) degrees of isolation that client transactions may specify, and describe algorithms to achieve these isolation levels. Then, we propose new levels of isolation that takeinto account the distributed nature of transaction execution, in terms of the lag of locally cached data with respect to the server database and discrepancies between local and remote reads. The SQL*Cache scheme is currently being implemented using a main memory database as the client-side cache, and commercial database servers as the backends. 1
Backbone Degradable Multiblock N-(2-Hydroxypropyl)methacrylamide Copolymer Conjugates via Reversible Addition−Fragmentation Chain Transfer Polymerization and Thiol−ene Coupling Reaction (2010)

Telechelic water-soluble HPMA copolymers and HPMA copolymer-doxorubicin (DOX) conjugates have been synthesized by RAFT polymerization mediated by a new bifunctional chain transfer agent (CTA) that contains an enzymatically degradable oligopeptide sequence. Postpolymerization aminolysis followed by chain extension with a bis-maleimide resulted in linear high molecular weight multiblock HPMA copolymer conjugates. These polymers are enzymatically degradable; in addition to releasing the drug (DOX), the degradation of the polymer backbone resulted in products with molecular weights similar to the starting material and below the renal threshold. The new multiblock HPMA copolymers hold potential as new carriers of anticancer drugs.
Type IV pilin is glycosylated in Pseudomonas syringae pv. tabaci 6605 and is required for surface motility and virulence (2012)

Type IV pilin (PilA) is a major constituent of pilus and is required for bacterial biofilm formation, surface motility and virulence. It is known that mature PilA is produced by cleavage of the short leader sequence of the pilin precursor, followed by methylation of N-terminal phenylalanine. The molecular mass of the PilA mature protein from the tobacco bacterial pathogen Pseudomonas syringae pv. tabaci 6605 (Pta 6605) has been predicted to be 12 329 Da from its deduced amino acid sequence. Previously, we have detected PilA as an approximately 13-kDa protein by immunoblot analysis with anti-PilA-specific antibody. In addition, we found the putative oligosaccharide-transferase gene tfpO downstream of pilA. These findings suggest that PilA in Pta 6605 is glycosylated. The defective mutant of tfpO (ΔtfpO) shows reductions in pilin molecular mass, surface motility and virulence towards host tobacco plants. Thus, pilin glycan plays important roles in bacterial motility and virulence. The genetic region around pilA was compared among P. syringae pathovars. The tfpO gene exists in some strains of pathovars tabaci, syringae, lachrymans, mori, actinidiae, maculicola and P. savastanoi pv. savastanoi. However, some strains of pathovars tabaci, syringae, glycinea, tomato, aesculi and oryzae do not possess tfpO, and the existence of tfpO is independent of the classification of pathovars/strains in P. syringae. Interestingly, the PilA amino acid sequences in tfpO-possessing strains show higher homology with each other than with tfpO-nonpossessing strains. These results suggest that tfpO and pilA might co-evolve in certain specific bacterial strains.
Gene expression markers of Tumor Infiltrating Leukocytes (2016)

Abstract Background Assays of the abundance of immune cell populations in the tumor microenvironment promise to inform immune oncology research and the choice of immunotherapy for individual patients. We propose to measure the intratumoral abundance of various immune cells populations with gene expression. In contrast to IHC and flow cytometry, gene expression assays yield high information content from a clinically practical workflow. Previous studies of gene expression in purified immune cells have reported hundreds of genes showing enrichment in a single cell type, but the utility of these genes in tumor samples is unknown. We describe a novel statistical method for using co-expression patterns in large tumor gene expression datasets to validate previously reported candidate cell type marker genes, and we use this method to winnow previously published gene lists down to a subset of high confidence marker genes. Methods We use co-expression patterns in 9986 samples from The Cancer Genome Atlas (TCGA) to validate previously reported cell type marker genes. We compare immune cell scores derived from these genes to measurements from flow cytometry and immunohistochemistry. We characterize the reproducibility of our cell scores in replicate runs of RNA extracted from FFPE tumor tissue. Results We identify a list of 60 marker genes whose expression levels quantify 14 immune cell populations. Cell type scores calculated from these genes are concordant with flow cytometry and IHC readings, show high reproducibility in replicate RNA samples from FFPE tissue, and reveal an intricate picture of the immune infiltrate in TCGA. Most genes previously reported to be enriched in a single cell type have co-expression patterns inconsistent with cell type specificity. Conclusions Due to their concise gene set, computational simplicity and utility in tumor samples, these cell type gene signatures may be useful in future discovery research and clinical trials to understand how tumors and therapeutic intervention shape the immune response.
Abstract #1069: Tigatuzumab (CS-1008), a novel humanized DR5 agonist antibody, eradicates pancreas cancer stem cells and results in long term cures, in combination with gemcitabine, in direct pancreas cancer xenografts (2009)

Background and Aim: Pancreatic adenocarcinoma remains one of the most deadly and chemo resistant cancers. Emerging data suggest that pancreatic cancer contains a small subset of distinct cancer stem cells that are responsible for tumor initiation, growth and are thought to be the major culprit behind cancer metastasis and recurrence after clinical remission. Treatment with standard chemotherapeutics may result in tumor shrinkage, but majority of the tumors recur, likely because the cancer stem cells survives and fuels tumor regeneration. Agents specifically targeting pancreatic cancer stem cells will likely be needed for tumor eradication and improve the poor prognosis of pancreatic cancer patients. To this end, we evaluated the antitumor potential of a novel humanized death receptor-5 (DR5) agonist antibody, Tigatuzumab (CS-1008), in combination with gemcitabine in pancreatic tumor xenografts. Experimental procedure: Flow cytometry was used to examine the expression of DR5 by pancreas cancer stem cells (ALDH+CD24+CD44+). Ten patient-derived tumor xenografts growing in nude mice were treated with 1) Tigatuzumab 3 mg/kg., i.v once weekly for 4 weeks 2) Gemcitabine 100 mg/kg i.p twice weekly for 4 weeks and 3) Gemcitabine + Tigatuzumab in the above mentioned dose and frequency. Tumor size was measured twice per week and relative tumor growth index and tumor doubling time was calculated versus control mice. Immunohistochemical staining was performed to determine the ALDH and CD24 expression in control and treated tumor samples. Results: Pancreas cancer stem cells are relatively enriched for DR5 expression (94% of ALDH+ cells and 89% of CD24+CD44+ cells) compared to non-stem cell bulk populations (30%). Gemcitabine treatment alone reduced tumor size and resulted in the enrichment of tumor cells that express ALDH+ and/or CD24+CD44+. But tumors reliably recurred after treatment discontinuation. However, treatment with gemcitabine + Tigatuzumab eliminated the pancreas cancer stem cells, significantly increased tumor doubling time and resulted in long term cures in 50% of cases. Conclusion: Pancreas cancer stem cells express DR5. Targeting DR5 with Tigatuzumab eliminates pancreatic cancer stem cell population and potentiates gemcitabine sensitivity. This study supports the rational to test this promising combination in a clinical setting of pancreatic cancer. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1069.
Eyeing the Camera: Into the Next Century (2002)

In the two centuries of photography, there has been a wealth of invention and innovation aimed at capturing a realistic and pleasing full-color two-dimensional representation of a scene. In this paper, we look back at the historical milestones of color photography and bring into focus a fascinating parallelism between the evolution of chemical based color imaging starting over a century ago, and the evolution of electronic photography which continues today. The second part of our paper is dedicated to a technical discussion of the new Foveon X3 multi-layer color image sensor; what could be descried as a new more advanced species of camera sensor technology. The X3 technology is compared to other competing sensor technologies; we compare spectral sensitivities using one of many possible figures of merit. Finally we show and describe how, like the human visual system, the Foveon X3 sensor has an inherent luminance-chrominance behavior which results in higher image quality using fewer image pixels.
Development of a clinical hepatic encephalopathy staging scale (2007)

This study confirms that the evaluation of multiple neurological manifestations is not necessary to classify hepatic encephalopathy adequately, which can be simply undertaken by an assessment of the patient's orientation, alertness, ability to respond to commands and to talk. A list of nine items is proposed as a linear scale from normality (Clinical Hepatic Encephalopathy Staging Scale = 0) to deep coma (Clinical Hepatic Encephalopathy Staging Scale = 9).
Elucidating the effects of postinduction glutamine feeding on the growth and productivity of CHO cells (2014)

Inducible mammalian expression systems are increasingly being used for the production of valuable therapeutics. In such system, maximizing the product yield is achieved by carefully balancing the biomass concentration during the production phase and the specific productivity of the cells. These two factors are largely determined by the availability of nutrients and/or the presence of toxic waste metabolites in the culture environment. Glutamine is one of the most important components of cell culture medium, since this substrate is an important building block and source of energy for biomass and recombinant protein production. Its metabolism, however, ultimately leads to the formation of ammonia, a well known inhibitor of cellular growth and productivity. In this work, we show that nutrient feeding post-induction can greatly enhance the product yield by alleviating early limitations encountered in batch. Moreover, varying the amount of glutamine in the feed yielded two distinct culture behaviors post-induction; whereas excess glutamine allowed to reach greater cell concentrations, glutamine-limited fed-batch led to increased cell specific productivity. These two conditions also showed distinctive lactate metabolism. To further assess the physiological impact of glutamine levels on the cells, a comparative (13) C-metabolic flux analysis was conducted and a number of key intracellular fluxes were found to be affected by the amount of glutamine present in the feed during the production phase. Such information may provide useful clues for the identification of physiological markers of cell growth and productivity that could further guide the optimization of inducible expression systems.
Eicosapentaenoic acid free fatty acid prevents and suppresses colonic neoplasia in colitis‐associated colorectal cancer acting on Notch signaling and gut microbiota (2014)

Inflammatory bowel diseases are associated with increased risk of developing colitis-associated colorectal cancer (CAC). Epidemiological data show that the consumption of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) decreases the risk of sporadic colorectal cancer (CRC). Importantly, recent data have shown that eicosapentaenoic acid-free fatty acid (EPA-FFA) reduces polyp formation and growth in models of familial adenomatous polyposis. However, the effects of dietary EPA-FFA are unknown in CAC. We tested the effectiveness of substituting EPA-FFA, for other dietary fats, in preventing inflammation and cancer in the AOM-DSS model of CAC. The AOM-DSS protocols were designed to evaluate the effect of EPA-FFA on both initiation and promotion of carcinogenesis. We found that EPA-FFA diet strongly decreased tumor multiplicity, incidence and maximum tumor size in the promotion and initiation arms. Moreover EPA-FFA, in particular in the initiation arm, led to reduced cell proliferation and nuclear β-catenin expression, whilst it increased apoptosis. In both arms, EPA-FFA treatment led to increased membrane switch from ω-6 to ω-3 PUFAs and a concomitant reduction in PGE2 production. We observed no significant changes in intestinal inflammation between EPA-FFA treated arms and AOM-DSS controls. Importantly, we found that EPA-FFA treatment restored the loss of Notch signaling found in the AOM-DSS control and resulted in the enrichment of Lactobacillus species in the gut microbiota. Taken together, our data suggest that EPA-FFA is an excellent candidate for CRC chemoprevention in CAC.
Immunocytochemical demonstration of early appearing astroglial structures that form boundaries and pathways along axon tracts in the fetal brain (1993)

During normal development of the mammalian forebrain, the paired cerebral hemispheres are initially separated midsagittally by the connective tissue-filled longitudinal fissure. During subsequent stages, the hemispheres fuse as basal lamina is remodeled and fibroblasts are eliminated from the fissure to create new central nervous system (CNS) territory in the midline. Two axon pathways, the corpus callosum and dorsal callosal stria, eventually use this region as part of their pathway. In order to assess the possible role of glial cells in the fusion process and in the guidance of axons in this and several other areas of the forebrain, we have analyzed the developing brain in timed cat and mouse embryos with immunohistochemical and morphological techniques. With the use of astroglial-specific antibodies and electron microscopy, we have visualized two distinct, primitive astroglial structures associated with the cerebral midline, and seven more associated with other specific brain regions. The way in which one of these structures moves as a column along the hemispheric midline in synchrony with seam formation suggests the possibility that during morphogenesis of the telencephalon, astrocytes may aid in the fusion process. In addition, the compact assemblage, early appearance and location of this and the other glial structures in relation to well defined neuroanatomical landmarks or axon pathways suggest that they may transiently compartmentalize relatively large regions of the CNS and organize certain developing fiber systems by acting as guides or barriers at critical stages of ontogeny.
Prognostic utility of RIFLE for acute renal failure in patients with sepsis (2007)

Acute renal failure (ARF) is common among patients with sepsis and increases mortality [1]. However, the prognostic utility of the newly released classification for ARF, entitled RIFLE (Risk, Injury, Failure, Loss, and End-stage kidney disease) [2], in predicting mortality in such patients has not yet been assessed. We sought to evaluate retrospectively the usefulness of RIFLE in predicting mortality in patients with sepsis admitted to the infectious disease intensive care unit (ICU) of our hospital between January 2005 and December 2006. Data were collected from the unit database. Sepsis was classified in accordance with American College of Chest Physicians and the Society of Critical Care Medicine consensus [3]. Patients with chronic kidney disease on dialysis were excluded from the analysis. The Simplified Acute Physiology Score (SAPS) version II was calculated based on the worst variables recorded during the first 24 hours of ICU admission. Mortality was assessed at day 60 [2]. Forward stepwise multivariate regression analysis was employed to evaluate independent predictors of mortality. The goodness-of-fit was tested by means of the Hosmer-Lemeshaw statistic. Area under the receiver operating characteristic curve (AUROC) was employed to evaluate the prognostic accuracy of RIFLE and SAPS II. A two-tailed P < 0.05 was considered statistically significant.

One-hundred and eighty-two patients (mean age 56.2 ± 18.56 years; 120 male; 162 white) were analyzed. Fourteen patients had sepsis, 108 patients had severe sepsis and 60 patients had septic shock. Sixty-eight patients (37.4%) had ARF: 11 patients were in class 'risk' (in RIFLE), 21 patients were in class 'injury', and 36 patients were in class 'failure'. The mortality rate was 37.4%, and increased from classes 'normal' to 'failure' (normal, 9.6%; risk, 27.3%; injury, 28.6%; failure, 55%; P < 0.0001). Multivariate analysis including age above 60 years, sex, SAPS II above 50, comorbidity (namely cardiovascular disease), and RIFLE class revealed that SAPS II score above 50 (odds ratio 0.12, 95% confidence interval [CI] 0.04–0.29; P < 0.0001) and class 'failure' (odds ratio 3.59, 95% CI 1.44–8.94; P = 0.006) were independent predictors of mortality. Similarly, SAPS II score above 50 (AUROC 0.778, 95% CI 0.694–0.863; P < 0.0001) and ARF according to RIFLE (AUROC 0.725, 95% CI 0.63–0.81; P < 0.0001) had good prognostic accuracy.

In summary, ARF, based on RIFLE criteria, is common in patients with sepsis, and is associated with increased mortality. RIFLE appears to be a useful prognostic tool in such patients.
AmpliTaq ® DNA Polymerase, FS Dye-Terminator Sequencing: Analysis of Peak Height Patterns (1996)

Taq DNA polymerases in which the phenylalanine is substituted by a tyrosine at position 667 (Taq F667Y) are members of a new class of DNA polymerases that incorporate chain-terminating dideoxyribonucleoside triphosphates (ddNTPs) much more efficiently than the wild-type Taq DNA polymerase. Improved incorporation of ddNTPs into DNA during cycle sequencing using AmpliTaq DNA polymerase, FS (Taq-FS, a member of the Taq F667Y family), and dye-labeled primers results in nearly uniform peak heights in the sequencing trace. This is not the case when dye-labeled ddNTPs are used in Taq-FS cycle sequencing reactions. While the rate of dye-terminator incorporation is more efficient with Taq-FS, the peak pattern is still highly variable and different from that produced by the wild-type enzyme. We have systematically examined pairs of sequence-tagged sites that vary at only a single nucleotide to determine how base changes influence the peak heights of neighboring bases in sequencing traces generated by the Taq-FS dye-terminator chemistry. In 31 of 64 possible 3-base windows (48%), we find that the peak height of a particular base can be predicted by knowing just one or two bases 5' to the base in question. We have also compared and contrasted the peak patterns produced by the Taq-FS enzyme with those previously identified for the wild-type enzyme. Establishing the patterns in peak heights within local sequence contexts can improve the accuracy of base-calling and the identification of polymorphisms/mutations when using the Taq-FS dye-terminator cycle-sequencing chemistry.
Cellular Adhesion Mediated by Factor J, a Complement Inhibitor (1998)

Factor J (FJ) is a complement inhibitor that acts on the classical and the alternative pathways. We demonstrated FJ-cell interactions in fluid phase by flow cytometry experiments using the cell lines Jurkat, K562, JY, and peripheral blood lymphocytes. FJ bound to plastic plates was able to induce in vitro adhesion of these cells with potency equivalent to fibronectin. As evidence for the specificity of this reaction, the adhesion was blocked by MAJ2, an anti-FJ monoclonal antibody, and by soluble FJ. Attachment of the cells required active metabolism and cytoskeletal integrity. The glycosaminoglycans heparin, heparan sulfate, or chondroitin sulfates A, B, and C inhibited to varying degrees the binding of FJ to cells, as did treatment with chondroitinase ABC. In the search for a putative receptor, a protein of 110 kDa was isolated by affinity chromatography, and microsequence analysis identified this protein as nucleolin. Confocal microscopy evidenced the presence of nucleolin in cell membrane by immunofluorescence with monoclonal (D3) and polyclonal anti-nucleolin antibodies in Jurkat cells. The interaction FJ-nucleolin was evidenced by Western blot and enzyme-linked immunosorbent assay. Furthermore, purified nucleolin and D3 inhibited adhesion of Jurkat cells to immobilized FJ, suggesting that the interaction was specific and that nucleolin mediated the binding.