gebhart/patrepeval huggingface dataset:
Weakening of the Gram-negative bacterial outer membrane - A tool for increasing microbiological safety (2007)

Gram-negative bacteria are harmful in various surroundings. In the food industy their metabolites are potential cause of spoilage and this group also includes many severe or potential pathogens, such as Salmonella. Due to their ability to produce biofilms Gram-negative bacteria also cause problems in many industrial processes as well as in clinical surroundings. Control of Gram-negative bacteria is hampered by the outer membrane (OM) in the outermost layer of the cells. This layer is an intrinsic barrier for many hydrophobic agents and macromolecules. Permeabilizers are compounds that weaken OM and can thus increase the activity of antimicrobials by facililating entry of hydrophobic compounds and macromolecules into the cell where they can reach their target sites and inhibit or destroy cellular functions. \n\nThe work described in this thesis shows that lactic acid acts as a permeabilizer and destabilizes the OM of Gram-negative bacteria. In addition, organic acids present in berriers, i.e. malic, sorbic and benzoic acid, were shown to weaken the OM of Gram-negative bacteria. Organic acids can poteniate the antimicrobial activity of other compounds. Microbial colonic degradation products of plant-derived phenolic compounds (3,4-dihydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 3,4-dihydroxyphenylpropionic acid, 4-hydroxyphenylpropionic acid, 3-phenylpropionic acid and 3-hydroxyphenylpropionic acid) efficiently destabilized OM of Salmonella. The studies increase our understanding of the mechanism of action of the classical chelator, ethylenediaminetetra-acetic acid (EDTA). In addition, the results indicate that the biocidic activity of benzalkonium chloride against Pseudomonas can be increased by combined use with polyethylenimine (PEI). In addition to PEI, several other potential permeabilizers, such as succimer, were shown to destabilize the OM of Gram-negative bacteria. Furthermore, combination of the results obtained from various permeability assays (e.g. uptake of a hydrophobic probe, sensitization to hydrophobic antibiotics and detergents, release of lipopolysaccharide (LPS) and LPS-specific fatty acids) with atomic force microscopy (AFM) image results increases our knowledge of the action of permeabilizers.
<title>TEM<formula><inf><roman>00</roman></inf></formula> Mode Ho:YLF Laser</title> (1980)

A flashlamp pumped liquid nitrogen cooled Ho:YLF laser was constructed and operated both normal mode and Q-switched. In normal mode operation, the laser produced over 300 mj at 2.9 percent slope efficiency but it operated on several lines. Lasing was restricted to one line and Q-switched operation was achieved up to 150 mj.
JC polyomavirus mutants escape antibody-mediated neutralization (2015)

JC polyomavirus (JCV) persistently infects the urinary tract of most adults. Under conditions of immune impairment, JCV causes an opportunistic brain disease, progressive multifocal leukoencephalopathy (PML). JCV strains found in the cerebrospinal fluid of PML patients contain distinctive mutations in surface loops of the major capsid protein, VP1. We hypothesized that VP1 mutations might allow the virus to evade antibody-mediated neutralization. Consistent with this hypothesis, neutralization serology revealed that plasma samples from PML patients neutralized wild-type JCV strains but failed to neutralize patient-cognate PML-mutant JCV strains. This contrasted with serological results for healthy individuals, most of whom robustly cross-neutralized all tested JCV variants. Mice administered a JCV virus-like particle (VLP) vaccine initially showed neutralizing "blind spots" (akin to those observed in PML patients) that closed after booster immunization. A PML patient administered an experimental JCV VLP vaccine likewise showed markedly increased neutralizing titer against her cognate PML-mutant JCV. The results indicate that deficient humoral immunity is a common aspect of PML pathogenesis and that vaccination may overcome this humoral deficiency. Thus, vaccination with JCV VLPs might prevent the development of PML.
The heterogeneous linkage of economic policy uncertainty and oil return risks (2019)

The recent financial crisis and its aftermath boost the research of economic policy uncertainty and its relevant topics. In this paper, we forecast the oil return risks based on the CAViaR method and further depict the dynamic and heterogeneous features during the crisis (or non-crisis) period, as well as in different markets via DCC-GARCH models. The empirical results show the linkage of economic policy uncertainty and oil return risks, indicating an increasing trend and stronger relationship with major events. Further study shows the heterogeneous feature existing during crisis or non-crisis period, and there is heterogeneity in values and variations of their linkage in different markets. Therefore, policymakers should intervene timely in the crude oil market, release good news, and stabilize oil prices during the crisis period. During the non-crisis period, however, investors need to rationally analyze the price trend of the oil market, thereby preventing possible risks in the market.
Genetics of Nitrofurazone Resistance in Escherichia coli (1978)

Wild-type Escherichia coli cells are sensitive to nitrofurazone (NF) and many other nitrofuran derivatives. A variety of evidence indicated that these compounds are converted to toxic "active" metabolites by reductases present in the bacteria. Sensitive E. coli K-12 acquired threefold-greater resistance to NF in one mutational step. These partially resistant mutants could undergo a second mutation that made them 10 times as resistant as the wild type. Mutation of wild-type strain K-12 to the higher level of resistance in a single step was not observed. The first mutational step was associated with partial loss of reduced nicotinamide adenine dinucleotide phosphate-linked, O(2)-insensitive NF reductase activity, and the second step was associated with loss of the remaining activity. The two-step mutants did, however, contain other NF reductases that were inhibited by O(2) and reduced NF only under anaerobic conditions. We designated the genes that control reductase activity "nitrofuran sensitivity genes" (nfsA and nfsB). Thus, wild-type strains are nfsA(+)nfsB(+), and the resistant double mutants are nfsA nfsB. A variety of crosses established that these genes are both located close to gal, that the most probable sequence is lac nfsB gal nfsA, and that the single-step mutants with an intermediate level of resistance are nfsA nfsB(+). The nfsA(+)nfsB strains contained about 70 to 80% of the wild-type reductase I activity-apparently enough to confer wild-type sensitivity. This reductase activity was resistant to 2 M urea. The nfsA nfsB(+) strains had only 20 to 30% of the wild-type activity, and this residual activity was sensitive to 2 M urea.
Growth Factors Regulate Transin Gene Expression by c- fos -Dependent and c- fos -Independent Pathways (1988)

The rapid induction of the proto-oncogene c-fos by growth factors and other bioactive agents, and the recent evidence that the c-fos protein (Fos) is associated with transcriptional complexes, suggests that Fos may represent an integral part of an intracellular messenger pathway that triggers changes in gene expression and ultimately phenotypic alterations. This report examines the role of c-fos in growth factor stimulation of transin, a matrix-degrading secreted metalloproteinase. Platelet-derived growth factor (PDGF) stimulation of transin RNA was blocked by a selective reduction in Fos synthesis with antisense c-fos mRNA, whereas epidermal growth factor (EGF) stimulation of transin occurred despite an equivalent inhibition of Fos levels. The stimulatory effect of both PDGF and EGF on transin transcription involved factors recognizing the sequence TGAGTCA, which is found in the transin promoter and is reported to be a binding site for the transcriptional factor Jun/AP-1 and for associated Fos and Fos-related complexes. Thus both Fos-dependent and Fos-independent pathways exist for growth factor regulation of gene expression, and both effects may be mediated through the same cis-acting transcription element.
Biomarker panel diagnosis of thyroid cancer: a critical review (2008)

The accurate preoperative diagnosis of thyroid cancer continues to be a significant challenge for those individuals who present with nodular thyroid disease, particularly for tumors with indeterminate cytomorphological features by fine-needle aspiration biopsy. In an effort to develop improved diagnostic tools, a number of studies have investigated the discriminatory potential of many different RNA and protein molecules. However, no individual thyroid cancer biomarker has been found with sufficient sensitivity and specificity. Therefore, research focus has shifted to panels of multiple markers with the hope of improved performance and robustness. A panel comprised of GAL3, CK19 and HBME1 is by far the most studied to date and offers some improvement over individual marker performance alone. However, relatively few marker panels have been studied and their performances and application as diagnostic tests have not been consistently reported. We present a comprehensive review of molecular marker panel studies for thyroid tumors and current issues and challenges. In the future, studies evaluating larger numbers of biomarkers in large patient cohorts are required for the development and validation of a clinically applicable test.
A phase 1 study of MEDI4736, an anti–PD-L1 antibody, in patients with advanced solid tumors. (2014)

3001^ Background: Immune-suppressing molecules such as PD-L1 can be co-opted by cancer cells to suppress the natural immune response to cancer. Upregulation of PD-L1 and inhibition of antitumor T-cell activation is observed in several tumor types. MEDI4736 is a human IgG1 antibody which binds specifically to PD-L1, preventing binding to PD-1 and CD80. Methods: An ongoing phase 1 multicenter, open-label study (NCT01693562) is evaluating safety, pharmacokinetics (PK), and antitumor activity of MEDI4736 given IV every 2 (q2w) or 3 wks (q3w) in a 3+3 dose escalation with a 28-day (q2w) or 42-day (q3w) dose-limiting toxicity (DLT) window, followed by expansion in 8 solid tumors. Response was assessed by immune-related response criteria in escalation. Results: As of Jan 17, 2014, 26 patients (pts) (13 NSCLC, 8 melanoma, 5 other) in dose escalation (median age 59 yrs; 35-77), all PS 0-1, with a median of 4 prior treatments, received a median of 5 (1-25) q2w and 4.5 (1-7) q3w doses of MEDI4736 across 6 cohorts (0.1 – 10 mg/kg q2w; 15 mg/kg q3w). MEDI4736 showed dose-dependent PK. Evidence of ADA impacted PK exposure in only 1 patient. No DLTs or maximum tolerated dose were identified for q2w or q3w dosing. Treatment-related AEs occurred in 34% of pts, all Grade 1-2; none led to discontinuation of study drug. The most frequent treatment-related AEs were diarrhea, fatigue, rash, and vomiting (12% each). No pneumonitis, colitis, or hyperglycemia occurred. Of 26 pts, 4 PRs (3 NSCLC, 1 melanoma) and 5 additional pts with tumor shrinkage not meeting PR were observed. Disease control rate (PR + SD ≥ 12 wks) was 46%. Tumor shrinkage, as early as 6 wks, was seen at all dose levels, and benefit was durable; 11 pts remain on study as of the data cutoff (2+ to 14.9+ mos). Expansion cohorts opened Sep 2013 using a 10 mg/kg q2w dose; 151 pts have been dosed, with the opportunity to enroll > 600 pts. Preliminary clinical activity has been observed with acceptable safety across a range of tumors including SCCHN, pancreatic, gastric, NSCLC, and melanoma. Conclusions: MEDI4736 has demonstrated an acceptable safety profile and durable clinical activity in this dose-escalation study. Expansion in multiple cancers and development of MEDI4736 as monotherapy and in combination is ongoing. Clinical trial information: NCT01693562.
Free-Radical Ring-Opening Polymerization (1984)

Abstract Although the ionic ring-opening polymerization of heterocyclic compounds, such as ethylene oxide, tetrahydrofuran, ethylen-imine, β-propiolactone, and caprolactam, as well as the Ziegler-Natta ring-opening of cyclic olefins, such as cyclopentene and norbornene, are well known, free radical ring-opening polymerizations are rather rare. The few examples that are reported in the literature involve cyclopropane derivatives or highly strained bi-cyclic olefins. For example, Takahashi [l] studied the free radical polymerization of vinylcyclopropane and reported that the cyclopropane ring opened to give a polymer containing about 80% 1,5-units and about 20% of undetermined structural units.
Expressing the relationships between multiple views in requirements specification (1993)

Composite systems generally comprise heterogeneous components whose specifications are developed by many development participants. The requirements of such systems are invariably elicited from multiple perspectives which will overlap, complement and contradict each other. If these requirements are developed and specified using multiple methods and notations respectively, then it is necessary to express and check the relationships between the resultant specification fragments. In this paper we deploy multiple “ViewPoints” that hold partial requirements specifications, described and developed using different representation schemes and development strategies. We discuss the notion of interViewPoint communication in the context of this ViewPoints framework, and propose a general model for such communication. We elaborate on some of the requirements for expressing and enacting inter-ViewPoint relationships, and use fragments of the requirements specification method CORE to illustrate our model.
Associations of Four Circulating Chemokines with Multiple Atherosclerosis Phenotypes in a Large Population-Based Sample: Results from the Dallas Heart Study (2010)

Specific chemokines contribute to vascular inflammation and may be useful biomarkers to detect atherosclerosis. The chemokines CXCL1 and CCL11 have previously been studied in animal or human models of atherosclerosis, while CXCL2 and CCL23 have not. Among 2,454 subjects enrolled in the Dallas Heart Study, a multi-ethnic population-based sample, we measured plasma CCL11, CCL23, CXCL1, and CXCL2, and associated levels with coronary artery calcium (CAC) by computed tomography, and aortic wall thickness, plaque burden, and compliance by magnetic resonance imaging. Elevated chemokine levels were defined as greater than or equal to the median for CCL11 and CCL23 and greater than or equal to the upper detection limit for CXCL1 and CXCL2. Elevated CCL23 (P < 0.01) and CXCL1 (P = 0.01), but not CCL11 and CXCL2, associated with CAC in univariable analyses. After adjustment for traditional risk factors, elevated CCL23 remained associated with CAC (OR 1.3, 95% CI 1.0-1.7; P = 0.02), while the association with CXCL1 was modestly attenuated (OR 1.4, 95% CI 1.0-2.1; P = 0.06). CCL23 also associated with aortic wall thickness, plaque, and compliance in univariable analyses (P < 0.05 for each), but these associations were attenuated after multivariable adjustment. The novel chemotactic protein, CCL23, which has not been previously studied in atherosclerosis, is independently associated with coronary atherosclerosis, suggesting that this chemokine merits further study in animal and human models.
<title>Computer Controlled Automatic Test Facility For Fiber Optic Transmission Systems</title> (1983)

A computer controlled automated test facility has been developed by Bell-Northern Research for the laboratory evaluation of fiber-optic digital transmission equipment over a range of environmental, electrical and optical stress conditions. The system, named Fiber Optic System Test (FROST), is currently used to verify the design integrity and performance of short wavelength (850 nm) fiber-optic transmission equipment operating at the DS-2 (6.312 Mb/s) and DS-3 (44.736 Mb/s) rates in the digital hierarchy. It can also test equip-ment operating at the DS-1 (1.544 Mb/s) rate. This paper presents the basic system design, describes the implementation and outlines the capabilities of the system. The automated test system has provided data on the equipment being tested which supplemented and expanded information obtained from system trials carried out under field conditions. It permits the rapid verification of improvements in equipment design and enables tests to be carried out on several systems simultaneously, which would be time consuming and expensive if undertaken using manual control. The effectiveness of the test program using the FROST facility has led to the system being enhanced to accommodate long wavelength fiber-optic digital transmission systems. It also has potential applications as a Computer Aided Manufacturing tool.
Exploiting predisposition in the stereoselective synthesis of mono-, bi- and tetracyclic oxygen heterocycles: Equilibration between, and trapping of, alternative di- and tetraacetals (2003)

The desymmetrisation of 1,4-difuran-2-ylbutane-1,4-diol by Sharpless asymmetric oxidation gave the corresponding desymmetrised product in > 96% ee. However, the product existed as a mixture of two interconverting isomers, both of which were mixtures of anomers. The product could be trapped in high yield with a range of reagents to give stable adducts with embedded pyran-3-one, 1,6-dioxaspiro[4.5]decane or pyrano[3,2-b]pyran ring systems. The strategy was also applied in the interconversion between alternative tetracycles and, under acidic conditions, this process was thermodynamically controlled. The selectivity of the process was rationalised by molecular modelling using the HF/6-31G* parameter set.
Meiosis in hematological malignancies. In situ cytogenetic morphology. (1996)

This is the first study on the in situ cytogenetic morphology and analysis of malignant bone marrow cells, growing attached on a culture vessel surface. It was documented that bone marrow cells, in different types of hematological malignancies, divide by meiosis giving rise to a non-repetitive aneuploidy. Male and female gametes are formed by meiosis and fertilization occurs in a life cycle of: [sequence see text] Immature and mature somatic oocytes were evidenced by prophase stages of the first and diploid or hypodiploid or haploid metaphases identical to those of the second human, ovarian oocytic meiotic division, showing "XX" or "XY" sex chromosomes in female or male patients respectively. Nuclear vlimata were the male gametes showing a condensed head with tail morphology. Metaphases of nuclear vlimata were aneuploid, keeping the head with tail shape, carrying chromosomes identical to those of human spermatogonia. Somatic metaphases identical to those of human spermatocytes in meiosis II and spermatogonia were demonstrated. The process of fertilization was documented by nuclear vlima invasion into host cell metaphases, by metaphases of fertilized oocyte showing both the female chromosome "0" and the male chromatids "s" and hybrid metaphases of oocytic with somatic chromosomes. Meiosis was characterized by nuclear extrusion of chromosomes, meiotic, condensed chromosomes, nuclear vlimata, metaphase and nuclear fusion, hybrid metaphases, nuclear budding, nuclear conglomerates, nuclear bridges, chromosomal fusion substance, transfer of chromosomes and non-repetitive aneuploidy. Meiotic, Double Minute, ring and minute chromosomes extruded by nuclei were loaded with glycoproteins, glycosaminoglycans and calcium-activated neutral proteinase, distinguishing them from mitotic chromosomes. The main characteristic events of meiosis, observed in malignant bone marrow cells, were also demonstrated in fungal and rat testicular cells, known to divide by meiosis.
Cloning and characterization of BAI2 and BAI3, novel genes homologous to brain-specific angiogenesis inhibitor 1 (BAI1) (1997)

We have identified two novel human genes homologous to BAI1 (brain-specific angiogenesis inhibitor 1), an angiogenesis inhibitor that is a candidate for involvement in development of glioblastoma. Like BAI1, these two genes, designated BAI2 and BAI3, were specifically expressed in brain, and are likely to be expressed in the same type of cells. However, in spite of similar tissue specificity among the three BAI genes, only BAI1 is transcriptionally regulated by p53. BAI3 expression was absent in two of nine glioblastoma cell lines examined and was significantly reduced in three of the remaining seven. These data suggest that members of this novel gene family may play important roles in suppression of glioblastoma. BAI1, BAI2 and BAI3 were mapped to 8q24, 1p35 and 6q12, respectively.
Prognostic implications of type and density of tumour-infiltrating lymphocytes in gastric cancer (2008)

The study aims to determine whether type and density of tumour-infiltrating lymphocytes (TILs) can predict the clinical course in gastric cancer. Gastric carcinomas (n=220) were immunostained for CD3, CD8, CD20, and CD45RO and evaluated for clinicopathologic characteristics. Number of TILs that immunostained positively for each marker were counted using NIH ImageJ software. Tumours were grouped into low- and high-density groups for each marker (CD3, CD8, CD45RO). The densities of CD3+, CD8+, and CD45RO+ TILs were found to be independent predictors of lymph node metastasis by multivariate analysis with odds ratios (95% CI) of 0.425 (0.204–0.885), 0.325 (0.150–0.707), and 0.402 (0.190–0.850), respectively. Kaplan–Meier survival analysis revealed that patients in the high-density groups for CD3, CD8, and C45RO had a significantly longer survival time than the patients in the corresponding low-density groups, respectively. In multivariate survival analysis, the densities of CD3+, CD8+, and CD45RO+ TILs remained independent prognostic factors with hazard ratios (95% CI) of 0.549 (0.317–0.951), 0.574 (0.347–0.949), and 0.507 (0.298–0.862), respectively. In conclusion, density of TILs was found to be independently predictive of regional lymph node metastasis and patient survival in gastric cancer.
A logical data model for integrated geographical databases (2002)

An approach to the design and the development of geographical database systems based on the integration of different specialized databases is investigated. This approach is supported by an extension of the relational model which makes it possible to separate interaction issues from integration issues, guaranteeing independence between the logical level and the physical level. The introduced extended logical model guarantees to the user a uniform and expressive view of geographical entities, while making it possible to refer to them and access them through both descriptive and geometrical/spatial characteristics. On the other hand, the logical model gives the designer a formal methodology and formal framework for the correct specification of the geographical information at the logical level.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthese von substituierten Benzo[b]thiophenen (1980)

Abstract Die Zimtsäuren 1 a‐t sowie deren Derivate l u, lv und 1 w lassen sich mit Thionylchlorid zu den Benzo[ b ]thiophenen 2a‐t bzw. 2v, w cyclisieren. 2a und 2 v, w konnten unabhängig aus den entsprechenden Alkinen mit Dischwefeldichlorid dargestellt werden.
4,5-Dihydroxypyrimidine Carboxamides and N-Alkyl-5-hydroxypyrimidinone Carboxamides Are Potent, Selective HIV Integrase Inhibitors with Good Pharmacokinetic Profiles in Preclinical Species (2006)

The dihydroxypyrimidine carboxamide 4a was discovered as a potent and selective HIV integrase strand transfer inhibitor. The optimization of physicochemical properties, pharmacokinetic profiles, and potency led to the identification of 13 in the dihydroxypyrimidine series and 18 in the N-methylpyrimidinone series having low nanomolar activity in the cellular HIV spread assay in the presence of 50% normal human serum and very good pharmacokinetics in preclinical species.