gebhart/patrepeval huggingface dataset:
Detection and Monitoring of Cell‐Free DNA in Blood of Patients with Colorectal Cancer (2008)

Cell-free tumor-specific and normal DNA are released into the blood circulation by cellular necrosis and apoptosis. We examined whether circulating DNA in blood of patients with colorectal cancer could be used as an additional marker for diagnosis and response to therapy. The concentration of circulating cell-free DNA in the blood of 55 patients with advanced colorectal cancer and 20 healthy donors was measured. One to four follow-up serum samples from 14 patients were also available. Patients with colorectal cancer had a wide range of DNA concentrations in their blood. The calculated values were between 22 and 3922 ng/mL DNA, with a mean and median value of 1157 ng/mL and 868 ng/mL, respectively. In contrast, the average concentration of cell-free DNA in the serum of healthy donors was significantly lower (5-16 ng/mL). During therapy the levels of serum DNA were not constant, but fluctuated, regardless of the chemotherapy used. High DNA levels of >1000 ng/mL of blood significantly correlated with a shorter survival (P= 0.02). Quantitative analysis demonstrates that elevated DNA levels can be detected in blood of patients with colorectal cancer and may be a useful tool in combination with other tumor markers for detection of colorectal cancer.
Residue Leu-641 of Acetyl-CoA Synthetase is Critical for the Acetylation of Residue Lys-609 by the Protein Acetyltransferase Enzyme of Salmonella enterica (2005)

Posttranslational regulation of protein function by acetylation is present throughout nature. Regulation of protein function by Sir2 protein (sirtuin) deacetylases is conserved in all domains of life. In the prokaryote Salmonella enterica, the metabolic enzyme acetyl-coenzyme A synthetase (Acs) is regulated by a Sir2-dependent protein acetylation/deacetylation system (SDPADS). The recent identification of the acetyltransferase enzyme responsible for the acetylation of Acs defined the SDPADS in prokaryotes. This report identifies one residue in Acs, Leu-641, which is critical for the acetylation of Acs by the protein acetyltransferase enzyme. In vivo and in vitro evidence shows that mutations at Leu-641 prevent the acetylation of Acs by protein acetyltransferase, maintain the Acs enzyme in its active state, and bypass the need for sirtuin deacetylase activity during growth on acetate.
PGE2 increases inflammatory damage inEscherichia coli-infected bovine endometrial tissue in vitro via the EP4-PKA signaling pathway† (2018)

Endometritis is the most common bovine uterine disease following parturition. The role of prostaglandin E2 (PGE2) in the regulation of endometrial inflammation and repair is well understood. Excess PGE2 is also generated in multiple inflammatory diseases, including endometritis. However, it remains unclear whether PGE2 is associated with pathogen-induced inflammatory damage to the endometrium. To clarify the role of PGE2 in pathogen-induced inflammatory damage, this study evaluated the production of PGE2, inflammatory factors, and damage-associated molecular patterns (DAMPs) in cultured Escherichia coli-infected bovine endometrial tissue. PGE2 production was significantly higher in E. coli-infected tissue, and in E. coli-infected tissue treated with 15-prostaglandin dehydrogenase (15-PGDH) inhibitors, as compared to uninfected tissue. Phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) were also upregulated in E. coli-infected tissue, while concentrations of arachidonic acid (AA), leukotrienes, DAMPs, and other proinflammatory factors increased. The accumulation of PGE2 clearly damaged the cultured tissue. Treatment with the COX-2, mPGES-1, EP4, and protein kinase A (PKA) inhibitors decreased the production of PGE2, inflammatory factors, and DAMPs, simultaneously alleviating the E. coli-induced endometrial tissue damage. Therefore, the PGE2 that was generated by COX-2 and mPGES-1 accumulated, and this pathogenic PGE2 increased inflammatory damage by upregulating inflammatory factors and DAMPs in E. coli-infected bovine endometrial tissue. This upregulation of inflammatory factors and DAMPs might be regulated by the EP4-PKA signaling pathway.
Predictive model performance (2013)

We study the accuracy of evaluation metrics used to estimate the efficacy of predictive models. Offline evaluation metrics are indicators of the expected model performance on real data. However, in practice we often experience substantial discrepancy between the offline and online performance of the models.
Suppression of Endogenous bcl-2 Expression by Antisense Treatment Exacerbates Ischemic Neuronal Death (2000)

Previous studies have shown that overexpression of bcl-2 in transgenic mice or by viral vectors protects the brain against cerebral ischemia. However, it is not known whether bcl-2, which is endogenously expressed in response to ischemia, exerts a protective effect. To address this question, the authors blocked the endogenous expression of bcl-2 after ischemia using antisense oligodeoxynucleotides (ODN). Antisense, sense, scrambled ODN, or vehicles were infused in the lateral ventricle of the rat for 24 hours after 30 minutes of temporary middle cerebral artery occlusion. Twenty-four hours later the brains were removed and bcl-2 protein expression was assayed by Western blot. Antisense ODN, but not sense or scrambled ODN treatment, significantly inhibited bcl-2 protein expression after ischemia. Bcl-2 protein expression was also studied 24 hours after 60 minutes of temporary middle cerebral artery occlusion in vehicle and antisense ODN-treated rats. After 60 minutes of ischemia and vehicle treatment, bcl-2 was expressed in many neurons in the ventral cortical mantle and the medial striatum. After antisense ODN treatment there were few neurons in this region expressing bcl-2, instead most neurons TUNEL labeled. Treatment with the antisense ODN, but not sense ODN, increased infarction volume as determined by cresyl violet staining 72 hours after ischemia compared with vehicle controls. These results suggested that endogenously expressed bcl-2 promoted survival in ischemic neurons and was not simply an epiphenomenon in neurons already destined to live or die.
Bacillus subtilis and other gram-positive bacteria : biochemistry, physiology, and molecular genetics (1993)

Gram-Positive Bacteria Metabolism and Regulation Cell Envelope Chromosome Structure Chromosome Replication, Modification, and Repair Genetic Exchange and Genetic Engineering Transcription and Translation Machinery Post-Exponential Phase Phenomena Bacteriophages Production of Commercial Products
Norepinephrine-stimulated PI hydrolysis in oligodendrocytes is mediated by alpha 1A-adrenoceptors. (1993)

Oligodendrocyte progenitors were labelled with [3H]-myo-inositol in order to determine the effect of adrenergic agents on the accumulation of [3H]-inositol phosphates (InsP). Both norepinephrine and phenylephrine, a selective alpha 1-adrenoceptor agonist, increased the formation of [3H]-InsP, while isoproterenol, a beta-adrenoceptor agonist, did not. Propranolol (beta) and yohimbine (alpha 2), two adrenoceptor antagonists, had no significant effect on the NE-stimulated [3H]-InsP formation. By contrast, the response to NE was significantly blocked by phenoxybenzamine and the alpha 1-receptor antagonist, prazosin. Pretreatment with chloroethylclonidine, which selectively inactivates alpha 1B receptors, had no effect on NE-induced [3H]-InsP formation, while WB4101 had high potency in inhibiting this response. Pertussis toxin, which inactivates certain G-proteins, caused a approximately 60% reduction. NE-stimulated formation of [3H]-InsP depended on extracellular calcium influx, because it was decreased by 55% and 75% by chelation with EGTA or the addition of 1 mM CdCl2, respectively. These results suggest that oligodendrocyte progenitors express alpha 1-adrenoceptors characteristic of the alpha 1A subtype.
태권도 고단자 여성의 골밀도와 체력특성 (1999)

The effect of fighting sport, TeaKwonDo, on bone density is unclear. To determine the TKD-induced influences on local bone density and physical fitness, we evaluated on long-term trained TKD players in 8 women(Carrier mean 7 year) and compared the results with those in 9 sedentary women. Bone densities were measured at lumbar level and proximal femur by DEXA method (Lunar DPX). Bone densities to the neck and greater trochanter in the TKD group were 3.1% and 2.5% higher then those in the normal group. there were no significant difference between two groups. in case of lumber level TKD group was also shown by 6.5% comparing to the normal group. However no significant difference was appeared between two groups, on the other hand, flexibility(sit and reach) and power (standing long jump) among fitness factors were higher in the TKD group, and were significantly recognized at four site in the TKD group were appeared in negative relationship(P＜.O1, over V=.74). There was negative relationship (P＜.O1) between sargent jump and femur neck site in the normal group. In conclusion, we think that bone density at specific site can be increased only when balanced diet and mechanical impact supply enough to cumulate bone mineral content during stimulating local bone site over the minimum effective strain. Because TKD player failed to control frequently their weight, their nutrient rather then mechanical strain may be always deficit to accumulate bone mineral content.
Recalcitrant trichophytic granuloma associated with NK-cell deficiency in a SLE patient treated with corticosteroid. (2001)

Although deep trichophytic infection often occurs in immunocompromised patients, the immune deficiency in such patients has not been clarified. A 28-year-old man who suffered from recalcitrant trichophytic granuloma and tinea universalis during treatment for SLE with corticosteroid is described here to define the immunological abnormalities. In addition to routine immunological tests, we evaluated the patient's innate and specific immune functions to dermatophytes, including T cell, natural killer (NK) cell and neutrophil functions and activation of the complement cascade. We measured the minimum inhibitory concentration (MIC) of itraconazole for the isolated fungus and its concentrations in the patient's serum and pus. Trichophyton (T.) rubrum was constantly isolated from the exudates of the patient's skin lesions, although the concentrations of itraconazole in his serum (198 ng/ml) and lesions (210 ng/ml) were sufficient to inhibit the growth of the isolated fungus in vitro. Specific cell-mediated immune responses, determined by T cell stimulation and IFN-gamma production, were evoked following stimulation with trichophytic antigens. The patient's innate immunity, assessed by activation of the complement cascade and neutrophil-mediated phagocytosis, was not impaired. The number of circulating NK cells was markedly decreased (0.2% of the peripheral blood mononuclear cells), and was associated with low NK cell activity against K-562 cells even though lymphopenia had improved. The deficiency of innate immunity mediated by NK cells might be responsible for a part of the persistence of trichophytic granuloma in our case. Dermatophytes usually affect the horny layer of the skin and do not invade the living layers because the host immune system uses various mechanisms to eliminate the fungi. Both specific T cell-mediated immunity and nonspecific immunological mechanisms provide host defense against fungal infections. An adaptive immune response is usually preceded by innate immune responses mediated by neutrophils, NK cells, and circulating proteins such as complement components and anti-microbial peptides. However, in patients with localized or systemic immunological defects, granulomatous cutaneous infection of dermatophytes mostly caused by trichophytic fungi may occur [1]. Trichophytic granuloma includes Majocchi's granuloma [2] and disseminated trichophytic granuloma [3]. Recently, we experienced a patient with trichophytic granuloma and tinea universalis caused by Trichophyton (T.) rubrum infection during treatment with corticosteroid for systemic lupus erythematosus (SLE). We describe the clinical details of this patient, focusing on his immunological defects which led to the persistence of the fungal infection.
The Accumulation of Glucose 6-Phosphate from Glucose and Its Effect in an Escherichia coli Mutant Lacking Phosphoglucose Isomerase and Glucose 6-Phosphate Dehydrogenase (1968)

Abstract When presented with glucose, an Escherichia coli mutant lacking both phosphoglucose isomerase and glucose 6-phosphate dehydrogenase accumulated, internally, high concentrations (approximately 50 mm) of glucose 6-phosphate. It also accumulated glucose in polysaccharide form. Other metabolism of glucose, if any, was very restricted. The accumulation of glucose 6-phosphate was associated with inhibition of growth on those carbon sources the metabolism of which requires functional fructose disphosphatase activity; inhibition of this enzyme in vitro by high concentrations of glucose 6-phosphate was shown.
Expression of the RET receptor tyrosine kinase and GDNFR-alpha in normal and leukemic human hematopoietic cells and stromal cells of the bone marrow microenvironment. (1997)

The RET proto-oncogene product is a receptor tyrosine kinase representing the signal-transducing molecule of a multisubunit surface receptor complex for the glial cell line-derived neurotrophic factor (GDNF), in which a novel glycosyl-phosphatidylinositol (PI)-linked protein (termed GDNFR-alpha) acts as the ligand-binding component. We have analyzed expression of RET and GDNFR-alpha in purified normal hematolymphopoietic cells, leukemia/lymphoma cell lines, and 154 primary samples from patients with hematopoietic malignancies encompassing different lineages and differentiation stages. Relatively low amounts of RET mRNA were found in early CD34+ hematopoietic progenitors, but RET transcripts appeared to increase after myelomonocytic maturation. No expression of RET was found in peripheral blood and tissue B and T lymphocytes. Analysis of human myelomonocytic cell lines was overall consistent with results obtained on purified normal cells. Accordingly, RET expression was mainly confined to acute myeloid leukemias (AMLs) displaying either monocytic (French-American-British M4 and M5) or intermediate-mature myeloid (M2 and M3) phenotypes, being less frequently detected in early myeloid (M0 and M1) AMLs. In contrast, RET mRNA was sporadically detected in B-cell tumors, whereas, among T-cell malignancies, RET transcripts were mainly detected in cells of postthymic and mature T-cell phenotype. RET broad detection in primary tumors was not paralleled by the mutual expression of GDNFR-alpha, which was detected only in 2 isolated primary samples and in 3 leukemia/lymphoma cell lines. However, GDNFR-alpha transcripts, in the absence of RET mRNA, were found in normal bone marrow stromal cells (BMSC), in BM fibroblasts, and in two osteoblast cell lines previously described to support normal hematopoiesis. In the presence of GDNF-receptors derived from BMSC by PI-specific phospholipase C cleavage, GDNF efficiently bound RET-expressing AML blasts and was functionally active by reducing their clonogenic growth and triggering the monocytic maturation of leukemic cells.
Shortest path search using tiles and piecewise linear cost propagation (2002)

In this paper we propose a new algorithm for finding shortest paths in a tile connection graph. This algorithm uses an exact piecewise linear cost model to guide our search of the compact tile graph. Unlike previous tile search algorithms, this algorithm always rinds a shortest path. Unlike the grid graph algorithms (which do find shortest paths), this algorithm searches the tile graph which is much smaller than the grid graph. The efficiency of our new approach is confirmed by our experiments comparing our new algorithm with the grid graph algorithms.
Ferric carboxymaltose in patients with restless legs syndrome and nonanemic iron deficiency: A randomized trial (2017)

In patients who responded to treatment, ferric carboxymaltose may require more time to stabilize restless legs syndrome than previously assumed. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Carcinoma of the cervix treated with radiation therapy I. A multi-variate analysis of prognostic variables in the gynecologic oncology group (1991)

Between 1977 and 1985, the Gynecologic Oncology Group (GOG) conducted three clinical trials in locally advanced carcinoma of the cervix, clinical Stages I to IVA as classified by the International Federation of Gynecology and Obstetrics (FIGO). All 626 patients had primary carcinoma of the cervix and underwent operative assessment of the para-aortic (PA) lymph nodes. Patients received standardized external radiation therapy to the pelvis or to the pelvis and PA lymph nodes followed by one or two brachytherapy applications. To date, no statistically significant differences in progression-free interval (PFI) or survival time have been identified between the randomization treatment arms on any of these studies. Basic similarities among these studies led us to pool these data to identify patient characteristics and tumor characteristics associated with an increased risk of treatment failure. Multi-variate analysis showed patient age, performance status (PS), PA lymph node status, tumor size, and pelvic node status to be significantly associated with PFI. When modeling for survival, all these factors and clinical stage and bilateral extension were significant.
Structure-activity relationships in the 2-arylcarbapenem series. Synthesis of 1-methyl-2-arylcarbapenems (1987)

The labile tert-butyldimethylsilyl esters of the azetidinones 6-8b served as the crucial synthons in the preparation of the potentially useful ylide pyridyl thio esters 18-20. These intermediates were utilized to synthesize a host of title carbapenems 25-30d, 32, and 49-53. The antimicrobial properties and DHP-I susceptibility of these carbapenems were studied with reference to thienamycin.
Prognostic factors and reporting of prostate carcinoma in radical prostatectomy and pelvic lymphadenectomy specimens (2005)

This paper, based on the activity of the Morphology-Based Prognostic Factors Committee of the 2004 World Health Organization-sponsored International Consultation, describes various methods of handling radical prostatectomy specimens for both routine clinical use and research purposes. The correlation between radical prostatectomy findings and postoperative failure is discussed in detail. This includes issues relating to pelvic lymph node involvement, detected both at the time of frozen section and in permanent sections. Issues of seminal vesicle invasion, including its definition, routes of invasion and relationship to prognosis, are covered in detail. The definition, terminology and incidence of extra-prostatic extension are elucidated, along with its prognostic significance relating to location and extent. Margins of resection are covered in terms of their definition, the etiology, incidence and sites of positive margins, the use of frozen sections to assess the margins and the relationship between margin positivity and prognosis. Issues relating to grade within the radical prostatectomy specimen are covered in depth, including novel ways of reporting Gleason grade and the concept of tertiary Gleason patterns. Tumor volume, tumor location, vascular invasion and perineural invasion are the final variables discussed relating to the prognosis of radical prostatectomy specimens. The use of multivariate analysis to predict progression is discussed, together with proposed modifications to the TNM system. Finally, biomarkers to predict progression following radical prostatectomy are described, including DNA ploidy, microvessel density, Ki-67, neuroendocrine differentiation, p53, p21, p27, Bcl-2, Her-2/neu, E-cadherin, CD44, retinoblastoma proteins, apoptotic index, androgen receptor status, expression of prostate-specific antigen and prostatic-specific acid phosphatase and nuclear morphometry.
Activities of new acridone alkaloid derivatives against Plasmodium yoelii in vitro. (1990)

Forty-seven new acridone alkaloid derivatives (SA compounds) were tested for antimalarial activity in vitro. At a concentration of 1.0 microgram/ml, six of these inhibited 50% or more of the incorporation of [3H]hypoxanthine into Plasmodium yoelii in vitro. The four most potent compounds, SA 3757, SA 3548, SA 3761 and SA 3499, showed 50% inhibitory concentration (IC50) values of 0.023 microgram/ml, 0.03 microgram/ml, 0.053 microgram/ml and 0.15 microgram/ml, respectively. The chemotherapeutic indexes of these four acridones, based on the ratio of the 50% lethal concentration (LC50) values for cell growth of L1210 cells to the IC50 for inhibition of uptake of [3H]hypoxanthine into P. yoelii, were calculated to be equal to or more higher (greater than 870, 263, 189 and greater than 133, respectively) than chloroquine diphosphate (315) or pyrimethamine (87).
CWR22: androgen-dependent xenograft model derived from a primary human prostatic carcinoma. (1994)

The long-term propagation of primary human prostate cancer (PCA) in vivo or in vitro has been rare. Most such PCAs are phenotypically different from most PCAs in humans; i.e., they make little prostate specific antigen and respond little, if at all, to androgen deprivation. A serially transplantable, primary human PCA, designated CWR22, exhibits a clonal cytogenetic aberration, causes high elevations of prostate specific antigen in the peripheral blood of nude mice, and is unusually responsive to androgen deprivation as compared with other xenografts. Studies of mRNA from CWR22 have demonstrated the expression of prostate specific antigen and the epidermal growth factor receptor family including erbB1/epidermal growth factor receptor, erbB2/neu, and erbB3, but not erbB4. A ligand for these receptors, the neu differentiation factor, is also expressed.
Hydrolytic stability of allylic and phenolic esters of some synthetic cannabinoids: A theoretical (AM1) study (1995)

The hydrolytic stability of allylic (IA) and phenolic (IB) esters of novel bifunctional nonpsychotropic cannabinoids, homologs of (+)3S,4S-7-hydroxy-Δ6-tetrahydrocannabinol, is of practical importance due to their possible use as prodrugs. The influence of the bulk and nature of various acyl groups as well as of their position on the base catalyzed hydrolysis has been examined theoretically. Differences (ΔΔHf) between semiempirical heats of formation (ΔHf) of products and reactants were calculated for the formation of the tetrahedral intermediates (IIA, B) which constitutes the rate-determining step of the process. An analysis of the ΔΔHf values and of the calculated optimized lowest energy geometries indicates that formation of II and thus the hydrolysis is most favorable for the trifluoroacetyl and trimethylammoniumacetyl as compared to acetyl, glycyl, and dialkylaminoacetyl esters. The bulk of the acyl group in a series of glycinate esters, increasing in the order COCH2NH2 < COCH2NMe2 < COCH2NEt2 < COCH2N(iPr)2 stabilizes I proportionally, by hindering formation of II. By comparing series IA and IB, the formation of II appears to be generally favored for the phenolic esters compared to the allylic esters due to the release of a more significant steric strain. © 1995 John Wiley & Sons, Inc.