Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammation and Infections as Risk Factors for Ischemic Stroke

Background— Inflammatory processes have fundamental roles in stroke in both the etiology of ischemic cerebrovascular disease and the pathophysiology of cerebral ischemia. We summarize clinical data on infection and inflammation as risk or trigger factors for human stroke and investigate current evidence for the hypothesis of a functional interrelation between traditional risk factors, genetic predisposition, and infection/inflammation in stroke pathogenesis. Summary of Review— Several traditional vascular risk factors are associated with proinflammatory alterations, including leukocyte activation, and predispose cerebral vasculature to thrombogenesis on inflammatory stimulation. Furthermore, accumulation of inflammatory cells, mainly monocytes/macrophages, within the vascular wall starts early during atherogenesis. During later disease stages, their activation can lead to plaque rupture and thrombus formation, increasing stroke risk. Inflammatory markers (eg, leukocytes, fibrinogen, C-reactive protein) are independent predictors of ischemic stroke. Chronic infections (eg, infection with Chlamydia pneumoniae or Helicobacter pylori) were found to increase the risk of stroke; however, study results are at variance, residual confounding is not excluded, and causality is not established at present. In case-control studies, acute infection within the preceding week was a trigger factor for ischemic stroke. Acute and exacerbating chronic infection may act by activating coagulation and chronic infections and may contribute to atherogenesis. Genetic predisposition of the inflammatory host response may be an important codeterminant for atherogenesis and stroke risk. Conclusions— Inflammation contributes to stroke risk via various interrelated mechanisms. Infectious diseases, traditional risk factors, and genetic susceptibility may cooperate in stimulating inflammatory pathways. Final proof of a causal role of infectious/inflammatory mechanisms in stroke pathogenesis is still lacking and will require interventional studies.
Intervention for improving the appropriateness of physician orders for oral medications in geriatric VIP patients during the journey to JCI accreditation

Correspondence: Quan Zhou Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310009, China Tel +86 571 8778 4615 Fax +86 571-8702 2776 Email zhouquan142602@zju.edu. cn Dear editor We read with great interest the study by Fadare et al, who assessed the prescribing pattern for elderly Nigerian outpatients and concluded that polypharmacy and the prescription of potentially inappropriate medications are major therapeutic issues in Nigeria, and there is a need for prescriber training and retraining with emphasis on the geriatric population. We completely agree with Fadare et al’s point of view that a low proportion of patients with potentially inappropriate medications highlights the importance of information technology in medication management. We discuss and share our perspectives in the following paragraphs. Geriatric patients may suffer from multiple chronic diseases and receive more medications compared to younger patients. Medication therapy management (MTM) services provide essential reviews of drug regimens and are increasingly recognized as beneficial to patient safety, improved health outcomes, and cost savings. Undoubtedly, the elderly patients especially need MTM services. The Joint Commission International (JCI) accreditation standard has strict requirements for rational drug use. Irrational drug use includes inappropriateness of the drug, dose, frequency and route of administration, real or potential drug–drug interactions (DDIs), allergies, therapeutic duplications, and variation from organization criteria for use. The study of Fadare et al indicates that irrational drug use is still a major issue internationally. Our hospital successfully passed JCI accreditation on Feb 24, 2013 and became the first accredited academic medical center hospital, globally. Very recently, we randomly evaluated the physician orders for oral medications in geriatric very important person (VIP) wards of our hospital before and after JCI accreditation so as to illustrate the effectiveness of clinical interventions during the journey to JCI accreditation. Geriatric patient information and indicators of rational drug use are presented in Table 1. The results of our survey show that the proportion of drug-related problems (DRPs) decreased significantly from 13.0% (before JCI accreditation) to 3.5% (after JCI accreditation) (P , 0.01). Statistically significant changes (as decreasing) in five indicators demonstrated statistically significant changes (P , 0.01 or P , 0.05), ie, DDIs with potential adverse consequences, therapeutic duplication or combination use of two drugs within the same therapeutic or structurally similar class, and inappropriate dosing time, dosing frequency and dosing route. Seven DDIs with potential adverse consequences occurred before JCI accreditation whereas no adverse DDIs Dovepress
Transcriptional analyses before and after suppression of immediate hypersensitivity reactions by CCR3 blockade in eyes with experimental allergic conjunctivitis.

PURPOSE To characterize the transcriptome of allergic conjunctivitis mediated by eosinophil-related chemokine receptor CCR3 and to identify a candidate for possible therapeutic intervention in eosinophilic inflammation of the eye. METHODS Mice were sensitized to ragweed pollen, and allergic conjunctivitis was induced by an allergen challenge. The induction of allergic conjunctivitis was used to determine whether an inhibition of CCR3 would suppress eosinophilic inflammation and the allergen-induced immediate hypersensitivity reaction. In addition, sensitized mice were treated with a CCR3 antagonist or an anti-CCR3 antibody before the allergen challenge. Eosinophilic inflammation was evaluated histologically at 24 hours after the allergen challenge. Transcriptional changes with or without a blockade of CCR3 were determined by microarray analyses. RESULTS Blockade of CCR3 significantly suppressed allergen-induced clinical signs, mast cell degranulation, and eosinophilic inflammation. Clustering analysis of the transcriptome during the early phase identified clusters of genes associated with distinct biological processes. A CCR2 ligand, monocyte chemoattractant protein (MCP)-1, was identified in the cluster of genes related to mast cell activation. MCP-1, an attractant of monocytes but not eosinophils, was in the top 10 transcripts among the genome and was suppressed by CCR3 blockade. Importantly, antibody blockade of MCP-1 suppressed the eosinophilic inflammation significantly. CONCLUSIONS CCR3 regulates not only the eosinophilic inflammation but also the clinical signs and mast cell degranulation. The CCR3-mediated transcriptome is characterized by many biological processes associated with mast cell activation. Among these CCR3-mediated processes, MCP-1 was found to be significantly involved in eosinophilic inflammation probably by an indirect pathway.
Analysis of impact of generating capacity constraints in Mexico's Sistema Interconectado Nacional using equivalent assisting unit approach

This paper presents the results of a reliability analysis of the generation adequacy of the Mexico's Sistema Interconectado Nacional (SIN), which is comprised of seven interconnected control areas (systems). Analysis was performed taking into account scheduled and forced unit outages, additions of new units, permanent shut down of obsolete units, load demand, additions of new tie lines, and forced outage rates of existing tie lines between areas. 2010 analysis includes the impact of interconnection between Mexico and Guatemala's Power System. Risk indexes -Loss of Load Expectation (LOLE) and the Loss of Energy Expectation (LOEE)- were computed using an analytical (recursive) method and applying the equivalent assisting unit approach. Results of a previous reliability analysis considering SIN as one single area [1] are compared with results considering interconnections between areas.
Impact of Antimicrobial Dosing Regimen on Evolution of Drug Resistance In Vivo: Fluconazole and Candida albicans

ABSTRACT Numerous factors have been theorized to affect the development of antimicrobial resistance, including those specific to the host, the organism, the environment, the drug, and the drug prescriber. One variable under the control of the prescriber is the drug dosing regimen. Dosing regimens can vary in dose level, dosing interval, and treatment duration. The current studies examined the relationships between antimicrobial dosing regimens and resistance development by use of an in vivo model. A murine model of systemic Candida albicans infection was used to examine resistance emergence during exposure to the triazole antifungal fluconazole. Data from this experimental model demonstrated that the more frequently administered dosing prevented selection of the isogenic resistant cell populations. Conversely, dosing regimens producing prolonged sub-MIC effects appeared to contribute to the outgrowth of isogenic resistant strains. The association between dosing and resistance emergence observed in the current investigation is disparate from that described for antimicrobial compounds with cidal killing characteristics. The inhibitory or static antimicrobial activity of the triazole compounds may explain these differences.
Detoxification of the Fusarium Mycotoxin Deoxynivalenol by a UDP-glucosyltransferase from Arabidopsis thaliana*

Plant pathogenic fungi of the genus Fusarium cause agriculturally important diseases of small grain cereals and maize. Trichothecenes are a class of mycotoxins produced by different Fusarium species that inhibit eukaryotic protein biosynthesis and presumably interfere with the expression of genes induced during the defense response of the plants. One of its members, deoxynivalenol, most likely acts as a virulence factor during fungal pathogenesis and frequently accumulates in grain to levels posing a threat to human and animal health. We report the isolation and characterization of a gene from Arabidopsis thaliana encoding a UDP-glycosyltransferase that is able to detoxify deoxynivalenol. The enzyme, previously assigned the identifier UGT73C5, catalyzes the transfer of glucose from UDP-glucose to the hydroxyl group at carbon 3 of deoxynivalenol. Using a wheat germ extract-coupled transcription/translation system we have shown that this enzymatic reaction inactivates the mycotoxin. This deoxynivalenol-glucosyltransferase (DOGT1) was also found to detoxify the acetylated derivative 15-acetyl-deoxynivalenol, whereas no protective activity was observed against the structurally similar nivalenol. Expression of the glucosyltransferase is developmentally regulated and induced by deoxynivalenol as well as salicylic acid, ethylene, and jasmonic acid. Constitutive overexpression in Arabidopsis leads to enhanced tolerance against deoxynivalenol.
X-rays from the Type II quasar in the hyperluminous infrared galaxy IRAS F15307+3252★

We report the detection of X-ray emission from the hyperluminous infrared galaxy IRAS F15307 + 3252 at z = 0.93 and its properties obtained from XMM‐Newton observations. Although the X-ray emission is very faint and the data are noisy, a prominent line-like feature in the observed 3‐4 keV range is inferred from both photometric and spectroscopic techniques. It indicates an X-ray spectrum dominated by 6.4-keV Fe Kα emission and the presence of a Compton-thick active galactic nucleus. Our estimate of the luminosity of the illuminating source (L 2‐10 keV 1 × 10 45 erg s −1 ), required to produce the observed Fe Kα emission in reflection from cold matter, means that the hidden quasar nucleus accounts for a significant fraction of the large bolometric luminosity. The soft X-ray emission below 2 keV is found to be spatially extended and probably of a separate origin. The temperature and bolometric luminosity (kT � 2k eVand L CL � 1 × 10 44 erg s −1 ) obtained from a thermal spectrum place this X-ray source on the L‐TX relation of galaxy clusters. The possible association with a galaxy cluster can be added to the list of remarkable similarities between IRAS F15307 + 3252 and another hyperluminous infrared galaxy IRAS 09104 + 4109 (z = 0.44), both of which have bolometric luminosities dominated by hidden quasar nuclei. Our result on IRAS F15307 + 3252 illustrates how difficult it is to detect Compton-thick Type II quasars at z = 1, particularly if their bolometric outputs do not rival the hyperluminous population.
ATPase senses systemic energy states and regulates feeding 1 behavior through glucose-inhibited neurons 2 3

Arcuate Na+,K+-ATPase senses systemic energy states and regulates feeding 1 behavior through glucose-inhibited neurons 2 3 Hideharu Kurita, Kai Y. Xu, Yuko Maejima, Masanori Nakata, Katsuya Dezaki, Putra 4 Santoso, Yifei Yang, Takeshi Arai, Darambazar Gantulga, Shinji Muroya, Alan K. Lefor, 5 Masafumi Kakei, Eiju Watanabe, Toshihiko Yada* 6 7 Department of Physiology, Division of Integrative Physiology, Jichi Medical University School 8 of Medicine, Shimotsuke, Tochigi 329-0498, Japan. 9 Department of Neurosurgery, Jichi Medical University School of Medicine, Shimotsuke, 10 Tochigi 329-0498, Japan. 11 Department of Surgery, Division of Cardiac Surgery, University of Maryland School of 12 Medicine, Baltimore, MD 21201, USA. 13 Department of Psychiatry, Imamura-bunin Hospital, Kagoshima, Kagoshima 890-0064, Japan. 14 Department of Surgery, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 32915 0498, Japan. 16 17 Articles in PresS. Am J Physiol Endocrinol Metab (June 16, 2015). doi:10.1152/ajpendo.00446. 2014
Symmetric Word Alignments for Statistical Machine Translation

In this paper, we address the word alignment problem for statistical machine translation. We aim at creating a symmetric word alignment allowing for reliable one-to-many and many-to-one word relationships. We perform the iterative alignment training in the source-to-target and the target-to-source direction with the well-known IBM and HMM alignment models. Using these models, we robustly estimate the local costs of aligning a source word and a target word in each sentence pair. Then, we use efficient graph algorithms to determine the symmetric alignment with minimal total costs (i. e. maximal alignment probability). We evaluate the automatic alignments created in this way on the German--English Verbmobil task and the French--English Canadian Hansards task. We show statistically significant improvements of the alignment quality compared to the best results reported so far. On the Verbmobil task, we achieve an improvement of more than 1% absolute over the baseline error rate of 4.7%.
The psychology of written composition

The subject of this book is the mental activities that go into composing written texts. For brevity we will often refer to the subject simply as writing, but the term should not be taken too literally. In this book we are not concerned with the physical act of writing, except insofar as it influences other processes. The mental activities of writing considered in our research are the same kinds of higher mental processes that figure in cognitive research on all aspects of human intelligence. They include goal setting, planning, memory search, problem solving, evaluation, and diagnosis. Writing is, of course, easily recognized as an activity in which a good deal of human intelligence is put to use. Its neglect, until very recently, by cognitive scientists is, however, easy to understand. Cognitive research has been gradually working its way from well-defined to ill-defined problems, from tasks that draw on limited knowledge to tasks that draw on large bodies of knowledge, and from tasks that are easily constrained experimentally to ones that are more susceptible to intentions of the participants. On all of these counts, writing lies far out on the yet-to-be-reached end of the continuum.
Identification of Human Hepatic Cytochrome P450 Enzymes Involved in the Biotransformation of Cholic and Chenodeoxycholic Acid

3α,7α,12α-Trihydroxy-5β-cholan-24-oic (cholic) and 3α,7α-dihydroxy-5β-cholan-24-oic (chenodeoxycholic) acids are the predominant hepatic and biliary bile acids of most mammalian species including humans. Cholic and chenodeoxycholic acids are synthesized from cholesterol and accumulate in the liver during cholestasis. Biotransformation by hepatic cytochrome P450 (P450) enzymes represents a potentially effective pathway for elimination of these lipid-soluble bile acids. We developed a liquid chromatography/mass spectrometry-based assay to identify and quantify the human hepatic microsomal metabolites of cholic acid and chenodeoxycholic acid, and using a panel of human recombinant P450 enzymes, we determined the P450 enzymes involved. Incubation of cholic acid with human hepatic microsomes and NADPH produced a single metabolite, 7α,12α-dihydroxy-3-oxo-5β-cholan-24-oic (3-dehydrocholic) acid. Of the recombinant P450 enzymes tested, only CYP3A4 catalyzed 3-dehydrocholic acid formation. Similar experiments with chenodeoxycholic acid revealed the formation of 7α-hydroxy-3-oxo-5β-cholan-24-oic acid and 3α,6α,7α-trihydroxy-5β-cholan-24-oic (γ-muricholic) acid as major metabolites and 3α-hydroxy-7-oxo-5β-cholan-24-oic (7-ketolithocholic) acid and cholic acid as minor metabolites. Among the human recombinant P450 enzymes examined, CYP3A4 exhibited the highest rates of formation for 7α-hydroxy-3-oxo-5β-cholan-24-oic acid and γ-muricholic acid from chenodeoxycholic acid. Formation of 7-ketolithocholic acid and cholic acid from chenodeoxycholic acid has not been reported previously and could not be attributed to any of the recombinant P450 enzymes tested. In conclusion, the predominant pathway for the biotransformation of both cholic and chenodeoxycholic acids in human hepatic microsomes was oxidation at the third carbon of the cholestane ring. This study highlights a major role for CYP3A4 and suggests a possible route for the elimination of these two bile acids.
DNA polymerase η lacking the ubiquitin-binding domain promotes replicative lesion bypass in humans cells

The Rad6-Rad18 mediated monoubiquitylation of proliferating cell nuclear antigen (PCNA) at lys 164 plays a crucial role in promoting the access of translesion synthesis (TLS) DNA polymerases (Pols) to PCNA in the replication fork stalled at a lesion site. Although a number of genetic and biochemical observations have provided strong evidence that TLS Pols bind PCNA at its interdomain connector loop (IDCL) via their PCNA-interacting protein (PIP) domain, a more recent proposal formulates that TLS Pols bind PCNA at two sites, to the IDCL via their PIP domain and to lys-164 linked ubiquitin (Ub) via their ubiquitin-binding domain. To ascertain the relative contributions of the PIP and Ub-binding zinc finger (UBZ) domains of human Polη in TLS, we have determined whether the C-terminal truncations of hPolη that contain the PIP1 domain but lack the UBZ and PIP2 domains can still function in TLS in human cells. Our observations that such C-terminally truncated proteins promote efficient TLS opposite a cis-syn TT dimer and confer a high degree of UV resistance to XPV cells provide unambiguous evidence that the binding of PCNA via its PIP domain is essential as well as sufficient for providing hPolη the ability to carry out TLS in human cells.
Feature Report: Mobile Culture: An Ethnography of Cellular Phone Uses in Teenagers’ Everyday Life

Seven years ago, we launched an intensive qualitative field research project on the question of the relationship between new technologies and people in their everyday life.1 Our first research project (1998–2000) focused on the convergence of media in the family context and its role in creating a family specific culture and social organisation. This ethnographically oriented study involved 19 Canadian families. Through a combination of different methods of investigation (individual interviews, family interviews, observations in situ, notebooks on everyday technologically mediated practices) we gathered a multi-faceted portrait of the integration of technologies in everyday life.2 What we found through the analysis of our empirical data (whether ethnographic or discursive), were indications of some form of creative cooperation between users and technologies. We discovered a world where humans and technological artefacts work together to create a variety of specific ‘ways of life’. Some of these were new and totally unexpected, while others were interesting ways to accomplish existing and even traditional social functions. This creative cooperation between people and technologies gave rise to a process of everyday cultural construction.
Drug resistance and molecular epidemiology of Mycobacterium tuberculosis in Mexico: a systematic review.

OBJECTIVE To compare drug resistance (DR) rates and genetic diversity of Mycobacterium tuberculosis strains from different states of Mexico. MATERIALS AND METHODS A systematic review of English and Spanish-language articles using MEDLINE and Google Scholar. Search terms included Mycobacterium tuberculosis, Mexico, resistance, mutation and epidemiology. RESULTS Fifteen studies for phenotypic DR rates (n=2 694), twelve studies for genotypic DR (n=748) and eleven studies for genetic diversity (n=2 044) met our inclusion criteria. Mean DR and multidrug resistance (MDR) rates were 37.5% and 20.6%, respectively. The most frequent mutations were rpoB531 (53.1%), katG315 (50.6%), embB306 (32.1%), rpsL43 (14.6%) and pncA359 (16.7%) in DR strains. Novel mutations were found. Predominant shared types were SIT53 (T1, n=188, 3.9%), SIT119 (X1, n=125, 6.9%), SIT19 (EAI2-Manila, n=80, 6.3%) and SIT42 (LAM9, n=77, 3.0%). SIT1 Beijing genotype has been reported in six states from Mexico. CONCLUSIONS DR and MDR rates continue to increase. Genetic diversity of M. tuberculosis strains in Mexico is high. Reports of Beijing strains are increasing.
The Value of Having Children as an Aspect of Adult Development

Abstract In an attempt to understand the meaning of parenthood as a function of life-cycle changes, we compared childless men and women in their 20s' perceived values of having children, with childless men and women in their 30s' perceptions of having children. The younger subjects expressed a greater desire to become parents than the older adults did and viewed parenthood as having greater personal value than the older adults did. A discriminant analysis revealed that the costs of parenthood, rather than the benefits, distinguished the older subjects from the younger, but that different costs were important for men than for women. The difference between the younger subjects' and the older subjects' perceived values of having children reflected a tendency toward an androgynous sex role identification, particularly for men.