Miracle-dz/UniFAR-FTUs huggingface dataset:
May 10, 2020 Polymorphisms in NFKB1 and TLR4 and Interaction with Dietary and Life Style Factors in Relation to Colorectal Cancer in a Danish

Maintenance of a balance between commensal bacteria and the mucosal immune system is crucial and intestinal dysbiosis may be a key event in the pathogenesis of colorectal cancer (CRC). The toll-like receptor 4 (TLR4) is an important pattern-recognition receptor that regulates inflammation and barrier function in the gut by a mechanism that involves activation of the nuclear factor – κ B (NF- κ B) transcription factor. Dietary and life style factors may impact these functions. We therefore used a Danish prospective case-cohort study of 1010 CRC cases and 1829 randomly selected participants from the Danish Diet, Cancer and Health cohort to investigate three polymorphisms in NFKB1 and TLR4 and their possible interactions with diet and life style factors in relation to risk of CRC. Homozygous carriage of the variant allele of the TLR4 /rs5030728 polymorphism was associated with increased risk of CRC (incidence rate ratio (IRR) = 1.30; 95% confidence interval (CI): 1.05 – 1.60; P = 0.02 (gene-dose model); IRR = 1.24; 95%CI: 1.01 – 1.51; P = 0.04 (recessive model)). Del-carri-ers of the NFKB1 /rs28362491 polymorphism had a 17%
Targeted disruption of the Nhe1 gene fails to inhibit b 1 -adrenergic receptor-induced parotid gland hypertrophy acinar cells

Targeted disruption of the Nhe1 gene fails to inhibit b 1 -adrenergic receptor-induced parotid gland hypertrophy. Am J Physiol Gastrointest Liver Physiol 280: G694–G700, 2001. —Chronic b 1 -adrenergic receptor activation results in hypertrophy and hyperplasia of rodent salivary gland acinar cells. Na 1 /H 1 exchanger isoform 1 (NHE1) regulates cell volume and the induction of cell proliferation in many tissues. To investigate the relationship between NHE1 and the response of parotid glands to b 1 -adrenergic agonists, we examined by Northern blot analysis NHE1 expression in saline-treated mice and mice 30 min and 2, 6, and 24 h after isoproterenol injection. NHE1 transcripts increased ; 50% by 2 h, and a more than twofold increase was noted at 24 h. Isoproterenol did not acutely increase Na 1 /H 1 exchanger activity; however, exchanger activity was signiﬁcantly ele-vated by 24 h. To test whether NHE1 activity is essential for inducing salivary gland hypertrophy in vivo, mice with targeted disruption of Nhe1 were treated with isoproterenol. NHE1 failed to inhibit isoproterenol-induced hypertrophy. These data directly demonstrate that acinar cell hypertrophy induced by chronic b 1 -adrenergic receptor stimulation occurs indepen-dently of NHE1 activity. autora-diographs Innotech, San Leandro, CA).
The Right to Self-determination under the FDRE Constitution: Issues, Challenges and the Way Forward

The 1995 FDRE Constitution established ethnic federalism and restructured the regions along ethnic linguistic lines. Thus the constitution has given much protection to nation, nationality and people of Ethiopia to have the right to self - determination up to and including secession as a solution to resolve past injustice and civil war. However, reality shows that Ethiopia is still very much controlled by central government, and the constitutional guaranteed rights of nationalities are not adequately implemented in a genuine manner. The most debating issue in the constitution has focused on the rights of nations, nationalities and peoples to secession and self-determination rather than establishing clear procedures for sufficient representation of the diverse ethnic groups in the government institutions. Really it is difficult to exercise secessionist self-determination in the context of Ethiopia which has been influenced by centuries of migration and interaction between ethnic groups, who have created a complex pattern of ethnic, linguistic and religious groups. The article thus attempts to highlight some of the outstanding controversial issues, and challenges of the external aspect of the right to self-determination. To this end, the study draws from extensive literature reviews, previous research works, and journal articles relating to the issue of the topic. And finally, conclusions and recommendations will be drawn.
Localizing Violations of Approximate Constraints for Data Error Detection

Error detection is key for data quality management [16, 34, 19]. Leveraging domain knowledge in the form of user-specified constraints is one of the major approaches to error detection [1]. A recent trend in error detection has been utilizing approximate constraints (ACs) that a relation is expected to satisfy only to a certain degree rather than completely. An example are the recently introduced statistical constraints [49], that allow the user to specify which correlations among attributes she expects to be present or absent in the data. Statistical constraints allow the user to express a broad range of statistical and causal domain knowledge. Extensive empirical investigations indicate that even traditional integrity constraints such as functional dependencies hold only approximately in real-world datasets [46]. Approximate functional dependencies (AFDs) have been a data cleaning tool for some time [17]. This thesis introduces a new technique for enhancing error detection with approximate constraints. Our starting observation is that approximate constraints are context-sensitive: the degree to which they are satisfied depends on the sub-population being considered. An error region is a subset of the data that violates an AC to a higher degree than the data as a whole, and is therefore more likely to contain erroneous records. For example, an error region may contain the set of records from before a certain year, or from a certain location. We describe an efficient algorithm for identifying distinct data regions that violate given ACs to different degrees, based on a recursive tree partitioning scheme. The learned trees describe different error regions in terms of data attributes that are easily interpreted by users (e.g. all records before 2003). This helps to explain to the user why some records were identified as likely errors. After identifying error regions, we can apply error detection methods to each error region separately, rather than to the dataset as a whole. Our empirical evaluation, done using four datasets containing both real world and synthetic errors, shows that identifying error regions increases both precision and recall of error detection based on ACs. Error regions can be combined not only with constraint-based error detection, but also with other approaches such as those based on machine learning. Our experiments provide evidence that the error regions boost the performance of machine learning methods.
the Central Extended to Fear and Anxiety.

It is widely thought that phasic and sustained responses to threat reflect dissociable circuits centered on the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST), the two major subdivisions of the central extended amygdala. Early versions of this hypothesis remain highly influential and have been incorporated into the National Institute of Mental Health Research ResearchDomainCriteriaframework.However,newobservationsencourageadifferentperspective.AnatomicalstudiesshowthattheCeandBSTformatightlyinterconnectedunit,wheredifferentkindsofthreat-relevantinformationcanbeintegratedandusedtoassemblestatesoffearandanxiety.ImagingstudiesinhumansandmonkeysshowthattheCeandBSTexhibitsimilarfunctionalprofiles. Bothregionsaresensitivetoarangeofaversivechallenges,includinguncertainortemporallyremotethreat;bothcovarywithconcurrentsignsandsymptomsoffearandanxiety;bothshowphasicresponsestoshort-livedthreat;andbothshowheightenedactivityduringsustainedexposuretodiffuselythreateningcontexts.Mechanisticstudiesdemonstratethatbothregionscancontroltheexpressionoffearandanxietyduringsustainedexposuretodiffusethreat. Theseobservationscompelareconsiderationofthecentralextendedamygdala’scontributionstofearandanxietyanditsroleinneuropsychiatricdisease.
Situações de conflito vivenciadas no contexto hospitalar: a visão dos técnicos e auxiliares de enfermagem

Realizamos un estudio en el Hospital de Clinicas UFMG (Minas Gerais, Brasil), objetivando analizar el modo en el que el enfermero se enfrenta con los conflictos en el ambiente organizacional. Desarrollamos la investigacion en dos fases de recoleccion de datos. Aplicamos un cuestionario y a continuacion realizamos una entrevista semiestructurada. Organizamos los datos de acuerdo a los contenidos tematicos. Segun los profesionales entrevistados, el termino conflicto acarrea una connotacion negativa. Algunos sujetos apuntaron los siguientes tipos de conflicto: intrapersonal, interpersonal e intergrupal. Determinado numero de entrevistados relato que el enfermero esta preparado para enfrentarse a situaciones de conflicto utilizando el dialogo y la negociacion. Entretanto, otros respondieron que el enfermero no esta preparado, en razon de la inexperiencia profesional y la falta de interaccion con el equipo. Consideramos que esos resultados apuntan a que el enfermero reflexione acerca de su conducta gerencial.
MicePersistence of Chronic Fungal Asthma in CXCR2 Is Necessary for the Development and

The role of CXCR during allergic airway and asthmatic diseases is yet to be fully characterized. Therefore, the present study addressed the role of CXCR2 during Aspergillus fumigatus -induced asthma. Mice deﬁcient in CXCR2 (CXCR2 (cid:1) / (cid:1) ) and wild-type counterparts (CXCR2 (cid:2) / (cid:2) ) were sensitized to A. fumigatus Ags and challenged with A. fumigatus conidia, and the resulting allergic airway disease was monitored for up to 37 days. At days 3 and 7 after conidia, CXCR2 (cid:1) / (cid:1) mice exhibited signiﬁcantly greater methacholine-induced airway hyperreactivity than did CXCR2 (cid:2) / (cid:2) mice. In contrast, CXCR2-deﬁcient mice exhibited signiﬁcantly less airway hyperresponsiveness than the wild-type control groups at days 14 and 37 after conidia. At all times after conidia, whole lung levels of IL-4, IL-5, and eotaxin/CC chemokine ligand 11 were signiﬁcantly lower in CXCR2 (cid:1) / (cid:1) mice than in the wild-type controls. Eosinophil and T cell, but not neutrophil, recruitment into the airways of A. fumigatus -sensitized CXCR2 (cid:1) / (cid:1) mice was signiﬁcantly impaired compared with wild-type controls at all times after the conidia challenge. Whole lung levels of IFN- (cid:3) , inﬂammatory protein-10/CXC ligand (CXCL) 10, and monokine induced by IFN- (cid:3) (MIG)/CXCL9 were signiﬁcantly increased in CXCR2 (cid:1) / (cid:1) mice compared with CXCR2 (cid:2) / (cid:2) mice at various times after conidia. Interestingly, at day 3 after conidia, neutrophil recruitment and airway hyperresponsiveness in CXCR2 (cid:1) / (cid:1) mice was mediated by inﬂammatory protein-10/CXCL10 and, to a lesser degree, MIG/CXCL9. Taken together, these data suggest that CXCR2 contributes to the persistence of asthmatic disease due to A. fumigatus . The Journal of Immunology, 2002, 168: 1447–1456.
Regulation of the Ca Gradient Across the Sarcoplasmic Reticulum in Perfused Rabbit Heart

Myocardial contractility depends on Ca 21 release from and uptake into the sarcoplasmic reticulum (SR). The Ca gradient between the SR matrix and the cytosol (SR Ca 21 gradient) is maintained by the SR Ca -ATPase using the free energy available from hydrolysis of ATP. The activity of the SR Ca -ATPase is not only dependent on the energy state of the cell but is also kinetically regulated by SR proteins such as phospholamban. To evaluate the importance of thermodynamic and kinetic regulation of the SR Ca 21 gradient, we examined the relationship between the energy available from ATP hydrolysis ( DGATP) and the energy required for maintenance of the SR Ca 21 gradient (DGCa21SR) during physiological and pathological manipulations that alter DGATP and the phosphorylation state of phospholamban. We used our previously developed F nuclear magnetic resonance method to measure the ionized [Ca] in the SR of Langendorff-perfused rabbit hearts. We found that addition of either pyruvate or isoproterenol resulted in an increase in left ventricular developed pressure and an increase in [Ca ]SR. Pyruvate increased DGATP, and the increase in the SR Ca 21 gradient was matched to the increase in DGATP; DGATP increased from 58.3 60.5 to 60.461. 0 kJ/mol (P,0.05), andDGCa21SR increased from 47.1 60.3 to 48.560. 1 kJ/mol (P,0.05). In contrast, the increase in the SR Ca gradient in the presence of isoproterenol occurred despite a decline in DGATP from 58.360.5 to 55.860. 6 kJ/mol. Thus, the data indicate that the SR Ca 21 gradient can be increased by an increase in DGATP, and that the positive inotropic effect of pyruvate can be explained by improved energy-linked SR Ca 21 handling, whereas the results with isoproterenol are consistent with removal of the kinetic limitation of phospholamban on the activity of the sarcoplasmic/endoplasmic reticulum Ca -ATPase, which allows the SR Ca 21 gradient to move closer to its thermodynamic limit. Ischemia decreases DGATP, and this should also have an effect on SR Ca 21 handling. During 30 minutes of ischemia, DGATP decreased by 12 kJ/mol, but the decrease in DGCa21SR was 16 kJ/mol, greater than would be predicted by the fall inDGATP and consistent with increased SR Ca 21 release and increased SR Ca 21 cycling. Because ischemic preconditioning is reported to decrease SR Ca 21 cycling during a subsequent sustained period of ischemia, we examined whether ischemic preconditioning affects the relationship between the fall in DGATP and the fall inDGCa21SR during ischemia. We found that preconditioning attenuated the fall in DGCa21SR during ischemia; the fall inDGCa21SR was of comparable magnitude to the fall in DGATP, and this was associated with a significant improvement in functional recovery during reperfusion. The data suggest that there is both thermodynamic regulation of the SR Ca 21 gradient by DGATP and kinetic regulation, which can alter the relationship between DGATP and DGCa21SR. (Circ Res. 1998;83:898-907.)
The anti-tumor effects of the combination of microwave 1 hyperthermia and lobaplatin against breast cancer cells in vitro and 2 in vivo

Background: 37 Breast cancer is the main lethal disease among females. The combination of 38 lobaplatin and microwave hyperthermia plays a crucial role in several kinds of cancer 39 in the clinic, but it’s possible mechanism in breast cancer has remained indistinct. Methods: 42 Mouse models were used to detect breast cancer progression. Cell growth was 43 explored with MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- 44 sulphonyl)-2H-tetrazolium) and colony formation assays. Cell migration and invasion 45 were investigated with a transwell assay. Cell apoptosis was probed with flow 46 cytometry. The expression of apoptosis-associated proteins was examined with 47 Western blots. 48 Combination treatment decreased breast cancer cell viability, colony formation, cell 51 invasion and metastasis. In addition, the treatment induced breast cancer cell 52 apoptosis and autophagy, activated the JNK signaling pathway, suppressed the 53 AKT/mTOR signaling pathway, and downregulated IAP and Bcl-2 family protein 54 expression. 55 56 Conclusion: 57 These results indicate that lobaplatin is an effective breast cancer antitumor agent. 58 Microwave hyperthermia was a useful adjunctive treatment. Combination treatment 59 was more efficient than any single therapy. The possible mechanism for this effect 60 was mainly associated with activation of the JNK signaling pathway, inactivation of 61 the AKT/mTOR signaling pathway and down regulation of the Bcl-2 and IAP 62 families. 63 Anaesthetics: Tribromoethanol. -Tribromoethanol and
Addictive Socioeconomic di ﬀ erences in the motivation to stop using e-cigarettes and attempts to do so

Introduction: In England, the use of electronic cigarettes as a smoking cessation aid has become more popular than any other aid. Previous research suggests that ex-smokers from lower social groups are more likely to use e-cigarettes compared to ex-smokers from more socially advantaged groups. The present study aimed to assess the association between baseline education, income and employment status and (1) baseline motivation to stop using e-cigarettes (2) attempts to stop using e-cigarettes during follow-up among current smokers, recent ex- smokers and long-term ex-smokers who use e-cigarettes. Methods: UK online longitudinal survey of smokers, ex-smokers and e-cigarette users, May/June 2016 (baseline) and September 2017 (follow-up). In logistic regression models, motivation to stop using e-cigarettes at baseline (n = 994) and attempts to stop using e-cigarettes at follow-up (n = 416) among current smokers and ex-smokers were regressed onto baseline educational attainment, income, employment status while adjusting for baseline demographics, vaping status, smoking and e-cigarette dependence. Results: (1) Respondents with higher education (OR = 1.36; 95% CI: 1.06 – 1.74) or higher income (OR = 1.52; 95% CI: 1.17 – 1.98) were more likely to be motivated to stop using e-cigarettes, but only in unadjusted analysis. (2) Again, in unadjusted analysis only, employment was associated with reduced odds of attempting to stop using e-cigarette (OR = 0.50; 95% CI: 0.32 – 0.79). Conclusion: Higher socio-economic status may be associated with higher motivation to stop vaping but with lower likelihood of trying to do so.
Prediction of the Evolution of Ceftazidime Resistance in Extended-Spectrum (cid:2) -Lactamase CTX-M-9

A random mutagenesis technique was used to predict the evolutionary potential of (cid:1) -lactamase CTX-M-9 toward the acquisition of improved catalytic activity against ceftazidime. Thirty CTX-M mutants were obtained during three rounds of mutagenesis. These mutants conferred 1- to 128-fold-higher MICs of ceftazidime than the parental enzyme CTX-M-9. The CTX-M mutants contained one to six amino acid substitutions. Mutants harbored the substitutions Asp240Gly and Pro167Ser, which were previously observed in clinical CTX-M enzymes. Additional substitutions, notably Arg164His, Asp179Gly, and Arg276Ser, were observed near the active site. The kinetic constants of the three most active mutants revealed two distinct ways of improving catalytic efﬁciency against ceftazidime. One enzyme had a 17-fold-higher k cat value than CTX-M-9 against ceftazidime. The other two had 75- to 300-fold-lower K m values than CTX-M-9 against ceftazidime. The current emergence of CTX-M (cid:1) -lactamases with improved activity
Unsupervised extraction of functional gene expression signatures in the bacterial pathogen Pseudomonas aeruginosa with eADAGE

While the large sets of publicly available gene expression data contain substantial information about relationships between mRNA expression profiles and genetic background, environment, and cellular state, cross experiment comparisons of public data are challenged by technical noise that masks biological signals. We previously showed that one could reveal biological signatures within compendia of expression data using an unsupervised neural network algorithm, called ADAGE, which excels at detecting patterns in noisy datasets. Here, we show that the generation and integration of multiple ADAGE models, resulting in an ensemble ADAGE (eADAGE), better identified biological pathways. For the bacterium Pseudomonas aeruginosa, our analysis found that on the order of 1000 samples were needed to build pathway-level gene expression signatures. The P. aeruginosa gene expression compendium contains experiments performed in 78 different media, and we used eADAGE to identify expression signatures associated with medium-type across multiple experiments. We identified a subset of media, including several complex media that were not designed to limit phosphate, in which P. aeruginosa exhibited a phosphate starvation response controlled by PhoB. Furthermore, while it was expected that PhoB activates the phosphate starvation response in low phosphate, our analyses found that PhoB was also active in moderate phosphate concentrations and predicted that activity required a second stimulus provided by a sensor kinase, KinB, which was validated in subsequent experiments including a screen of a histidine kinase knock out collection confirmed the specificity of its role in the activation of the Pho regulon. Algorithms that extract biological signal from large collections of public gene expression data, such as eADAGE, can highlight opportunities to discover mechanisms that are currently unrecognized from public data.
A Prospective Study of Clinico-Histopathological Correlation among Leprosy Patients Attending a Tertiary Referral Centre in Assam, in This Post Elimination Era

Background: Leprosy, also known as Hansen’s disease, is a chronic, infectious and treatable disease that primarily affects the skin and the peripheral nerves. Clinico-histopathological correlation of leprosy case assumes a pivotal role in early diagnosis and proper labeling of a case and thus leads to better management of patients. Aim: To study the clinical and histopathological correlation among leprosy patients attending a tertiary referral centre in this post elimination era. Materials & Methods: Study was conducted at a tertiary hospital during July, 2014 to June, 2015. Total 72 new cases of leprosy were selected purely on clinical ground (WHO criteria) attending dermatology OPD. Then these patients were subjected to slit skin smear examination and skin biopsy. Histopathological classifications of sections were done on the basis of the scheme put forth by Ridley (1974) and later it was correlated with the clinical classification across the Ridley-Jopling spectrum to evaluate the concordance among two. Results: Both clinically and histopathologically, BT constituted the predominant group 52.80% and 41.66% respectively. The overall clinico-histopathological correlation was seen in 41 cases (56.94%). Maximal concordance was noted in indeterminate leprosy (100%), followed by polar forms of leprosy i.e. LL (80%) & TT (75%). The least concordance was seen in mid-borderline leprosy (16.66%). Conclusion: This study highlights the importance of histopathological examination in assessing the leprosy cases as the under-treatment of MB cases will lead to persisters in the community and thus spread of disease and possible danger of drug resistance too in this era of elimination.
Protein Engineering Strategies for Sustained GLP-1R-Dependent Control of Glucose Homeostasis

The abbreviations are; cAMP: adenosine 3’5’-cyclic monophosphate, CNS: central nervous system, DPP-IV: dipeptidyl peptidase IV, FBG: fasting blood glucose, GLP-1: glucagon-like peptide, GLP-1R: GLP-1 receptor, HbA1c: hemoglobin A1c, GTT: glucose tolerance test, PK: pharmacokinetic profile