gebhart/patrepeval huggingface dataset:
An essential role for IL-17 in preventing pathogen-initiated bone destruction: recruitment of neutrophils to inflamed bone requires IL-17 receptor–dependent signals (2007)

IL-17 and its receptor are founding members of a novel family of inflammatory cytokines. IL-17 plays a pathogenic role in rheumatoid arthritis (RA)-associated bone destruction. However, IL-17 is also an important regulator of host defense through granulopoiesis and neutrophil trafficking. Therefore, the role of IL-17 in pathogen-initiated bone loss was not obvious. The most common form of infection-induced bone destruction occurs in periodontal disease (PD). In addition to causing significant morbidity, PD is a risk factor for atherosclerotic heart disease and chronic obstructive pulmonary disease (COPD). Similar to RA, bone destruction in PD is caused by the immune response. However, neutrophils provide critical antimicrobial defense against periodontal organisms. Since IL-17 is bone destructive in RA but a key regulator of neutrophils, we examined its role in inflammatory bone loss induced by the oral pathogen Porphyromonas gingivalis in IL-17RA-deficient mice. These mice showed enhanced periodontal bone destruction, suggesting a bone-protective role for IL-17, reminiscent of a neutrophil deficiency. Although IL-17RA-deficient neutrophils functioned normally ex vivo, IL-17RA knock-out (IL-17RA(KO)) mice exhibited reduced serum chemokine levels and concomitantly reduced neutrophil migration to bone. Consistently, CXCR2(KO) mice were highly susceptible to alveolar bone loss; interestingly, these mice also suggested a role for chemokines in maintaining normal bone homeostasis. These results indicate a nonredundant role for IL-17 in mediating host defense via neutrophil mobilization.
Copper(I) as a Homogeneous Catalyst for the Ullmann Reaction in Aqueous Solutions − The Transformation of 2-Bromobenzoate into Salicylate (2002)

The CuI-catalyzed transformation of 2-bromobenzoic acid (2-Br-BA) into salicylic acid (main product), benzoic acid, and diphenoic acid was studied. The reaction was monitored by UV/Vis spectroscopy, HPLC, and ESR. Up to 25 turnovers were achieved for low CuI concentrations. An intermediate was observed that was assigned to a complex between copper and a follow-up product of the aromatic acid, probably a complex with a copper−carbon σ-bond. The process is probably initiated by the formation of a d-π* complex of CuI with the aromatic ring of 2-Br-BA followed by the reaction with a second CuI ion. The effect of the addition of CH3CN or NH3 on the catalytic process is reported. Both were found to accelerate the process when present at relatively low concentrations and slow it down at higher concentrations. A side product, 2-aminobenzoate was observed in the presence of NH3.
Baeyer–Villiger Monooxygenases, an Emerging Family of Flavin‐Dependent Biocatalysts (2003)

Abstract Baeyer–Villiger monooxygenases (BVMOs) are flavoenzymes that catalyze a remarkably wide variety of oxidative reactions such as regio‐ and enantioselective Baeyer–Villiger oxidations and sulfoxidations. Several of these conversions are difficult to achieve using chemical approaches. Due to their selectivity and catalytic efficiency, BVMOs are highly valuable biocatalysts for the synthesis of a broad range of fine chemicals. For a long time, only one member of this class of flavin‐containing biocatalysts had been cloned and overexpressed which has limited their application for synthetic processes. Recently a number of new genes that encode BVMOs have been sequenced and overexpressed. In this paper the biocatalytic properties of recently cloned BVMOs are reviewed. Furthermore, the potential for obtaining novel BVMOs from sequenced genomes will be discussed.
Experimental Modification of the Western Electric #5 Electrolarynx to a Mouth-Type Instrument (1975)

A modification of the Western Electric No; 5A electrolarynx is described and evaluated. The modification involved insertion of a bypass plug into the circuitry of this necktype instrument thus converting it to a mouth-type electrolarynx. Intensity readings at the one-third octaves and intelligibility data were obtained with the modified instrument and with a Cooper-Rand electrolarynx. The instruments were judged to be equal in overall performance.
Core System and Disaster Management : Failure of the Sewol Ferry Disaster Response System (2014)

The purpose of this study is to seek for the core system in managing disasters: Failure of the Sewol disaster response system to manage crisis effectively and efficiently. This paper suggests five elements which form a core system as follows; value, institution, leadership, devotion, and expertise. First, it is the value that determine the direction of system operation in some situations like disaster, public issue, and events, etc. The fundamental problems of crisis and emergency management came from a lack of value and philosophy for disaster management in the case of Sewol ferry disaster. Second, for realizing the desirable value, a system has to make or build up an institution which can be accepted socially and legally by society members. In the case of disaster response in Korea, there are lots of ad hoc institutions of disaster response in the time of accident. Third, leadership is essential to the success of any system which should accomplish a common task. Government leaders dealing with catastrophic disaster, however, failed to work out a new framework to tackle catastrophic disasters. Fourth, devotion is a positively necessary element for completing the system's work. But disaster response actors did not get the devotion to their job and not receive training in maritime rescue operations. Finally, as jobs becomes more specialized, system become increasingly dependent on expertise to achieve goals. In the case of disaster management system, there was no expertise in the related and responsible government organizations.
The anti-inflammatory sesquiterpene lactone parthenolide suppresses IL-4 gene expression in peripheral blood T cells (2002)

Sesquiterpene lactones (SL) derived from Mexican India medicinal plants and parthenolide, the major SL from European feverfew, have raised considerable interest because of their anti-inflammatory and complex pharmacological action. Interleukin-4 (IL-4) is a key cytokine that influences the development of T helper 2 cells and plays an important role in the pathogenesis of allergic diseases. We show here that the anti-inflammatory parthenolide suppresses IL-4 expression at the mRNA and the protein levels in a dose-dependent manner. We demonstrate that parthenolide blocks NF-kappaB binding to two important IL-4 promoter regulatory elements and suppresses promoter activity upon T cell activation. Differences regarding the effects of parthenolide on expression levels of IL-4, IL-2 and IFN-gamma were observed. Parthenolide (2.5 microM) could completely suppress IL-4 protein levels secreted in anti-CD3/CD28-stimulated peripheral blood T cells from allergic and normal donors. Complete inhibition of IL-2 and IFN-gamma requires higher doses of parthenolide. So far, drugs directed against IL-4 expression have not been described. This finding raises the potential to develop parthenolide to treat IL-4-mediated allergic-like inflammation.
Digital Image Tamper Detection Technique Based on Spectrum Analysis of CFA Artifacts (2018)

Existence of mobile devices with high performance cameras and powerful image processing applications eases the alteration of digital images for malicious purposes. This work presents a new approach to detect digital image tamper detection technique based on CFA artifacts arising from the differences in the distribution of acquired and interpolated pixels. The experimental evidence supports the capabilities of the proposed method for detecting a broad range of manipulations, e.g., copy-move, resizing, rotation, filtering and colorization. This technique exhibits tampered areas by computing the probability of each pixel of being interpolated and then applying the DCT on small blocks of the probability map. The value of the coefficient for the highest frequency on each block is used to decide whether the analyzed region has been tampered or not. The results shown here were obtained from tests made on a publicly available dataset of tampered images for forensic analysis. Affected zones are clearly highlighted if the method detects CFA inconsistencies. The analysis can be considered successful if the modified zone, or an important part of it, is accurately detected. By analizing a publicly available dataset with images modified with different methods we reach an 86% of accuracy, which provides a good result for a method that does not require previous training.
Investigating the humoral immune response in chronic venous leg ulcer patients colonised with Pseudomonas aeruginosa (2010)

The ability to manage the bioburden in chronic wounds is most likely coupled to the humoral immune response of the patient. We analysed markers of systemic immune response in patients with chronic venous leg ulcers (CVLUs) colonised (no-systemic infection) with the opportunistic pathogen Pseudomonas aeruginosa. Sera from 44 clinically non infected patients with CVLUs were analysed for total IgM and IgG isotype 1-4, complement C3, mannose-binding lectin (MBL), interleukin (IL)-6, C-reactive protein (CRP) and specific anti-P. aeruginosa antibodies against exotoxin A, elastase and alkaline phosphatase. Concentrations of IL-6 versus CRP intercorrelated (β = 2.43 95% CI (1.34-4.34)), but were independent of P. aeruginosa colonisation. MBL deficiency (MBL < 500 ng/ml) correlated to high serum levels of IgG(1) (P = 0.038) consistent with a compensatory mechanism, but not related to presence of P. aeruginosa in the ulcers. Twenty-four patients (54.5%) were culture positive for P. aeruginosa, also conferring significantly high serum levels of complement C3 (P = 0.014), but only two of these had positive titres for antibodies against exotoxin A. All patient sera were negative for antibodies against elastase and alkaline phosphatase. Fluorescent in situ hybridization analysis on randomly selected culture-positive patients could not establish unambiguous presence of P. aeruginosa biofilms in the ulcers. A multiple regression model showed P. aeruginosa and systemic CRP as significant factors in deterioration of ulcer healing rate.
Probing Peroxisome Dynamics and Biogenesis by Fluorescence Imaging (2014)

Peroxisomes are the most recently discovered classical organelles, and only lately have their diverse functions been truly recognized. Peroxisomes are highly dynamic structures, changing both morphologically and in number in response to both extracellular and intracellular signals. This metabolic organelle came to prominence due to the many genetic disorders caused by defects in its biogenesis or enzymatic functions. There is now growing evidence that suggests peroxisomes are involved in lipid biosynthesis, innate immunity, redox homeostasis, and metabolite scavenging, among other functions. Therefore, it is important to have available suitable methods and techniques to visualize and quantify peroxisomes in response to various cellular signals. This unit includes a number of protocols that will enable researchers to image, qualify, and quantify peroxisome numbers and morphology-with both steady-state and time-lapse imaging using mammalian cells. The use of photoactivatable fluorescent proteins to detect and measure peroxisome biogenesis is also described. Altogether, the protocols described here will facilitate understanding of the dynamic changes that peroxisomes undergo in response to various cellular signals.
Emerging treatments for progressive myoclonus epilepsies (2020)

<b>Introduction</b>: Progressive myoclonus epilepsies (PMEs) are a group of neurodegenerative diseases, invariably leading to severe disability or fatal outcome in a few years or decades. Nowadays, PMEs treatment remains challenging with a significant burden of disability for patients. Pharmacotherapy is primarily used to treat seizures, which impact patients' quality of life. However, new approaches have emerged in the last few years, which try to curb the neurological deterioration of PMEs through a better knowledge of the pathogenetic process. This is a review on the newest therapeutic options for the treatment of PMEs.<b>Areas covered</b>: Experimental and clinical results on novel therapeutic approaches for the different forms of PME are reviewed and discussed. Special attention is primarily focused on the efficacy and tolerability outcomes, trying to infer the role novel approaches may have in the future.<b>Expert opinion</b>: The large heterogeneity of disease-causing mechanisms prevents researchers from identifying a single approach to treat PMEs. Understanding of pathophysiologic processes is leading the way to targeted therapies, which, through enzyme replacement or underlying gene defect correction have already proved to potentially strike on neurodegeneration.
Pyridines and Pyrimidines Mediating Activity against an Efflux-Negative Strain of <i>Candida albicans</i> through Putative Inhibition of Lanosterol Demethylase (2003)

The first step in ergosterol biosynthesis in Saccharomyces cerevisiae consists of the condensation of two acetyl coenzyme A (acetyl-CoA) moieties by acetoacetyl-CoA thiolase, encoded by ERG10. The inhibition of the sterol pathway results in feedback activation of ERG10 transcription. A cell-based reporter assay, in which increased ERG10 transcription results in elevated specific beta-galactosidase activity, was used to find novel inhibitors of ergosterol biosynthesis that could serve as chemical starting points for the development of novel antifungal agents. A class of pyridines and pyrimidines identified in this way had no detectable activity against the major fungal pathogen Candida albicans (MICs > 64 micro g. ml(-1)). However, a strain of C. albicans lacking the Cdr1p and Cdr2p efflux pumps was sensitive to the compounds (with MICs ranging from 2 to 64 micro g. ml(-1)), suggesting that they are efficiently removed from wild-type cells. Quantitative analysis of sterol intermediates that accumulated during growth inhibition revealed the accumulation of lanosterol at the expense of ergosterol. Furthermore, a clear correlation was found between the 50% inhibitory concentration at which the sterol profile was altered and the antifungal activity, measured as the MIC. This finding strongly suggests that the inhibition of growth was caused by a reduction in ergosterol synthesis. The compounds described here are a novel class of antifungal pyridines and pyrimidines and the first pyri(mi)dines to be shown to putatively mediate their antifungal activity against C. albicans via lanosterol demethylase.
Globotriaosylceramide (Gb3) content in HeLa cells is correlated to Shiga toxin-induced cytotoxicity and Gb3 synthase expression (2009)

Globotriaosylceramide (Gb3) and globotetraosylceramide (Gb4) are the proposed functional receptors for Shiga toxin (Stx). To elucidate the effect of Gb3 content on Stx-induced cytotoxicity in HeLa cells, we cloned HeLa cells and determined the correlation between glycolipids content and Stx-induced cytotoxicity. The 29 HeLa cell clone (HLCC) lines used showed a wide range of sensitivity to Stx, compared to Gb3-rich cells which were more sensitive, showing as little as 20% viability to 100 pg/ml Stx. In contrast, Gb3-deficient cells proved resistant as they were more than 80% viable to 100 ng/ml Stx. Gb3 content in the HLCC lines corresponded with Stxs-induced cytotoxicity as well as Gb3 synthase expression, but no correlation with Gb4 content was noted. These data show that Gb3 content, which is regulated by the expression of Gb3 synthase, determines the sensitivity of HeLa cells toward Stx.
[Interindividual differences in tolerance to shift work and characteristics of shift workers: relation between the quality and duration of sleep and certain worker characteristics]. (1992)

The investigation aimed at examining the relationship between the quality and duration of sleep on the one hand and various shift workers' characteristics on the other, as well as establishing whether sleep characteristics were congruent with some other indices of night shift tolerance. A total of 604 rotating shift workers working in a fast rotating shift system were administered a battery of questionnaires. The results showed that sleep quality was related to their many characteristics, especially to neuroticism, rigidity of sleeping habits, flexibility of habits, and relaxedness. Actually, the shift workers' characteristics accounted for a notable percentage (48%) of interindividual differences in sleep quality. However, there were fewer traits related to sleep duration than to sleep quality so that only a small percentage of interindividual differences in sleep duration could be explained (12-30%). Sleep quality proved to be a good indicator of night shift tolerance. The results concerning sleep duration indicated only sleep duration on the afternoon shift and days off, as well as average sleep duration in the complete shift cycle, to be relatively good indices of night shift tolerance.
Staphylococcus aureus α-Hemolysin Promotes Platelet-Neutrophil Aggregate Formation (2013)

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes severe hemorrhagic necrotizing pneumonia associated with high mortality. Exotoxins have been implicated in the pathogenesis of this infection; however, the cellular mechanisms responsible remain largely undefined. Because platelet-neutrophil aggregates (PNAs) can dysregulate inflammatory responses and contribute to tissue destruction, we investigated whether exotoxins from MRSA could stimulate formation of PNAs in human whole blood. Strong PNA formation was stimulated by toxins from stationary phase but not log phase CA-MRSA, and α-hemolysin was singularly identified as the mediator of this activity. MRSA exotoxins also caused neutrophil (polymorphonuclear leukocyte) activation, as measured by increased CD11b expression, although platelet binding was not driven by this mechanism; rather, α-hemolysin-induced PNA formation was solely platelet P-selectin dependent. These findings suggest a role for S. aureus α-hemolysin-induced PNA formation in alveolar capillary destruction in hemorrhagic/necrotizing pneumonia caused by CA-MRSA and offer novel targets for intervention.
Selective Killing of SMARCA2- and SMARCA4-deficient Small Cell Carcinoma of the Ovary, Hypercalcemic Type Cells by Inhibition of EZH2: <i>In Vitro</i> and <i>In Vivo</i> Preclinical Models (2017)

Abstract The SWI/SNF complex is a major regulator of gene expression and is increasingly thought to play an important role in human cancer, as evidenced by the high frequency of subunit mutations across virtually all cancer types. We previously reported that in preclinical models, malignant rhabdoid tumors, which are deficient in the SWI/SNF core component INI1 (SMARCB1), are selectively killed by inhibitors of the H3K27 histone methyltransferase EZH2. Given the demonstrated antagonistic activities of the SWI/SNF complex and the EZH2-containing PRC2 complex, we investigated whether additional cancers with SWI/SNF mutations are sensitive to selective EZH2 inhibition. It has been recently reported that ovarian cancers with dual loss of the redundant SWI/SNF components SMARCA4 and SMARCA2 are characteristic of a rare rhabdoid-like subtype known as small-cell carcinoma of the ovary hypercalcemic type (SCCOHT). Here, we provide evidence that a subset of commonly used ovarian carcinoma cell lines were misdiagnosed and instead were derived from a SCCOHT tumor. We also demonstrate that tazemetostat, a potent and selective EZH2 inhibitor currently in phase II clinical trials, induces potent antiproliferative and antitumor effects in SCCOHT cell lines and xenografts deficient in both SMARCA2 and SMARCA4. These results exemplify an additional class of rhabdoid-like tumors that are dependent on EZH2 activity for survival. Mol Cancer Ther; 16(5); 850–60. ©2017 AACR.
New York ADAP to cover new AIDS drugs plus viral load testing. (1996)

New York State, for the first time and after massive grass-roots lobbying, committed millions of State tax dollars to the local AIDS Drug Assistance Program (ADAP). No State has been hit harder by AIDS than New York. As of September 1, 1996, ADAP began covering HIV protease inhibitors, viral load evaluations, and other crucial anti-HIV and opportunistic infection agents, including nevirapine for HIV, cidofovir for CMV, and DaunoXome for Kaposi's sarcoma. Also, ADAP has now restored some of the most important benefits and coverages of medications that were eliminated in January.
Optimal Compartment Layout Design for a Naval Ship Using an Improved Genetic Algorithm (2002)

With the trend in modern naval ships towards less dense payloads, space layout design has become more important. Recent advances in computing science and increased understanding of methods for developing mathematical models, which form the basis of the space layout design, have helped with the development of a powerful design procedure. In this study, the compartment layout problem, which can be regarded as the space layout design of a naval ship, is represented as a mathematical model, and a compartment layout algorithm based on the genetic algorithm (GA) in order to solve the problem is proposed. Comparative testing shows that the proposed algorithm performs better than other existing algorithms for the optimal compartment layout design. Finally, the proposed algorithm is applied to the compartment layout problem of a naval ship and the computational results are compared with the actual compartment layout of the naval ship.