Miracle-dz/UniFAR-FTUs huggingface dataset:
Meta‐analysis of the association between the interleukin‐1A −889C/T polymorphism and Alzheimer's disease

No clear consensus has been reached on the Interleukin‐1A (IL‐1A) −889C/T polymorphism and Alzheimer's disease (AD) risk. In this meta‐analysis, 27 case–control studies were assessed to evaluate the possible association. Overall, positive associations of the IL‐1A −889C/T polymorphism with AD risk were found in allele comparison T vs. C (OR = 1.09, 95% CI = 1.01–1.18), recessive model TT vs. CT + CC (OR = 1.21, 95% CI = 1.01–1.45), and homozygote comparison (TT vs. CC; OR = 1.32, 95% CI = 1.04–1.67). In subgroup analysis stratified by ethnicity, significant associations were demonstrated in Caucasians but not in Asians. In subgroup analysis according to the age of onset, the data showed a significant association in patients with late‐onset AD in Caucasians but not in early‐onset AD. In conclusion, this meta‐analysis supports the idea that IL‐1A –889C/T polymorphism is capable of causing AD and LOAD susceptibility in Caucasians but not in Asians. © 2012 Wiley Periodicals, Inc.
High-resolution structure of a BRICHOS domain and its implications for anti-amyloid chaperone activity on lung surfactant protein C

BRICHOS domains are encoded in > 30 human genes, which are associated with cancer, neurodegeneration, and interstitial lung disease (ILD). The BRICHOS domain from lung surfactant protein C proprotein (proSP-C) is required for membrane insertion of SP-C and has anti-amyloid activity in vitro. Here, we report the 2.1 Å crystal structure of the human proSP-C BRICHOS domain, which, together with molecular dynamics simulations and hydrogen-deuterium exchange mass spectrometry, reveals how BRICHOS domains may mediate chaperone activity. Observation of amyloid deposits composed of mature SP-C in lung tissue samples from ILD patients with mutations in the BRICHOS domain or in its peptide-binding linker region supports the in vivo relevance of the proposed mechanism. The results indicate that ILD mutations interfering with proSP-C BRICHOS activity cause amyloid disease secondary to intramolecular chaperone malfunction.
Attenuated Poxvirus-Based Simian Immunodeficiency Virus (SIV) Vaccines Given in Infancy Partially Protect Infant and Juvenile Macaques Against Repeated Oral Challenge With Virulent SIV

Summary:An infant macaque model was developed to test pediatric vaccine candidates aimed at reducing HIV transmission through breast-feeding. Infant macaques were given multiple immunizations during the first 3 weeks of life with recombinant poxvirus vaccines expressing simian immunodeficiency virus (SIV) structural proteins Gag, Pol, and Env (ALVAC-SIV or modified vaccinia virus Ankara [MVA]-SIV). After repeated daily oral inoculations with virulent SIVmac251 at 4 weeks of age, significantly fewer ALVAC-SIV-immunized infants were infected compared with unimmunized infants. Monkeys not infected after oral challenge in infancy were rechallenged at 16 months of age or older by repeated weekly oral SIV exposure; unimmunized animals were infected after fewer SIV exposures than were animals vaccinated with ALVAC-SIV or MVA-SIV. When infected, ALVAC-SIV- and MVA-SIV-vaccinated animals also had reduced viremia compared with unimmunized animals. The results of these investigations suggest that immunization of human infants with poxvirus-based HIV vaccine candidates may offer protection against early and late HIV infection through breastfeeding.
Human Resource Information Systems in Jordanian Universities

The main purposes of this study are to explore the extent to which public Jordanian universities have adopted Human Resource Information System (HRIS) and to examine the current HRIS uses, benefits and barriers in these universities. A structured questionnaire was constructed based on other previous studies, it also pre-tested, modified and translated to capture data from HRIS users in Jordanian universities. The main findings of this study reveled that the quick response and access to information were the main benefits of HRIS implementation. While, the insufficient financial support; difficulty in changing the organization’s culture and lack of commitment from top managers were the main HRIS implementation barriers. The present study provides some insights into the performance and applications of HRIS in Jordanian universities that could help Human Resource Management (HRM) practitioners to get a better understanding of the current HRIS uses, benefits and problems, which in turn, will improve the effectiveness of HRIS in Jordanian universities.
Pulmonary arterial hypertension: yesterday, today, tomorrow.

With more than 25 centuries of efforts to resolve its mysteries, the pulmonary circulation continues to inspire and humble researchers, frustrate clinicians, and scare patients with pulmonary arterial hypertension (PAH). Its mysteries lie in lost manuscripts written in the 12th-century Syria; within the pages of one of the rarest books in history written in 1531 by an author burned alive with his books, condemned by the Inquisition; within a publication from a young urologist self-experimenting 30 years before he received the Nobel prize…What kind of disease is this one that in the age of planning missions to Mars, no medical therapy can save its victims? It is certainly a disease that deserves our respect. The objective of this compendium is to present the state of the art in PAH, but mostly emphasize its future, discussing several evolving theories on its pathogenesis. Its objective is also to comprehensively summarize our current clinical approach to the disease, with patients in mind. In addition to researchers, clinicians, health professionals, students, and residents, its target audience includes patients: the patients who suffer, desperate for answers, and the patients who, one way or another, not only participate in but also fund our research through their taxes and donations. In the age of instant and easy information dissemination, many patients are already quite informed when they visit a specialist. How do we describe the cutting-edge developments in this complex disease to the informed patient? It is not easy, but most would agree that only the expert who really understands his/her subject is able to describe it in lay terms and pass its main messages. Humbled by the complexity of PAH and its challenges, we need to focus on what drives all of us fighting this disease. In addition to our patients, it is scientific curiosity: PAH …
Human immunodeficiency virus‐associated malignant lymphoma in eastern Denmark diagnosed from 1990 to 1996: clinical features, histopathology, and association with Epstein‐Barr virus and human herpesvirus‐8

Abstract: The clinicopathological features of human immunodeficiency virus (HIV)‐associated lymphoma were investigated in a retrospective study of 85 adult patients in eastern Denmark diagnosed during the period 1990–1996. The possible pathogenetic role of Epstein‐Barr virus (EBV) and human herpesvirus 8 (HHV‐8) in these tumours was also studied. Seventy patients (82%) presented with extranodal disease and 26 (31%) had CNS involvement at diagnosis. Diffuse large cell B‐cell lymphoma was the most frequent histological subtype, comprising 65 of 79 cases available for microscopic re‐evaluation (82%) and including 20 of 23 evaluable patients with CNS lymphoma (87%). EBV RNA was demonstrated by in situ hybridization in 51 of 65 evaluable tumours (79%) and in 14 of 16 cases (88%) with CNS‐lymphoma. Three cases showed a T‐cell phenotype. The presence of HHV‐8 DNA was analysed by PCR in 32 cases. A strong band consistent with tumour cell infection was detected in only one case, weaker bands being seen in 4 cases. None of these patients had primary effusion lymphomas. In conclusion, Danish AIDS‐related lymphomas are of predominantly high‐grade B‐cell type with extranodal localization and atypical presentation. Our results provide further evidence that EBV plays a major role in the pathogenesis of large cell AIDS‐related lymphoma, whereas HHV‐8 does not appear to contribute significantly to the development of solid lymphomas in this group of patients.
Papanicolaou smears of atypical glandular cells of undetermined significance: histological correlations and suggestions for management.

OBJECTIVE We sought to correlate cervical and endometrial neoplasias with Papanicolaou (Pap) smears of atypical glandular cells of undetermined significance (AGUS) and to suggest management. MATERIALS AND METHODS One hundred seventy-one patients with AGUS Pap smears were followed prospectively with colposcopy, biopsies, endocervical curettage, and endometrial biopsies. RESULTS One hundred twelve patients (65%) with AGUS Pap smears favoring reactive changes were found to harbor 13 preinvasive and invasive cervical squamous neoplasias and 1 ovarian sarcoma (total, 12.5% of patients with smears). Fifty-nine patients (35%) with AGUS Pap smears favoring neoplastic changes harbored 25 preinvasive and invasive squamous and glandular cervical and endometrial neoplasias (42.3%). CONCLUSION In the presence of an AGUS Pap smear favoring reactive changes, colposcopy, biopsies, and endocervical curettage should be performed. Endometrial biopsy should be added when AGUS Pap smear favors neoplasia.
Integration of digital repositories through federated queries using semantic technologies

Currently, institutions store the information that they produce in digital repositories, especially those within the academic scope, such as universities and libraries. However, the lack of agreement in defining protocols, meta-data descriptions and technologies for publication has caused issues while trying to integrate repositories. Numerous alternatives have been proposed to tackle this problem, however, most of them are based on syntactical technologies, which are exclusive to the ambit of digital repositories, hampering a higher level integration(Web). In addition, much of the research done so far uses centralized approaches, which are hardly scalable and can threaten to inter-institutional independence. In this work a new distributed integration architecture is proposed, which is based on semantic technologies and federated queries. This architecture has been successfully tested to integrate a group of institutional repositories belonging to universities, demonstrating its applicability within this context.
Adult T‐cell leukemia cells are characterized by abnormalities of Helios expression that promote T cell growth

Molecular abnormalities involved in the multistep leukemogenesis of adult T‐cell leukemia (ATL) remain to be clarified. Based on our integrated database, we focused on the expression patterns and levels of Ikaros family genes, Ikaros, Helios, and Aiolos, in ATL patients and HTLV‐1 carriers. The results revealed profound deregulation of Helios expression, a pivotal regulator in the control of T‐cell differentiation and activation. The majority of ATL samples (32/37 cases) showed abnormal splicing of Helios expression, and four cases did not express Helios. In addition, novel genomic loss in Helios locus was observed in 17/168 cases. We identified four ATL‐specific short Helios isoforms and revealed their dominant‐negative function. Ectopic expression of ATL‐type Helios isoform as well as knockdown of normal Helios or Ikaros promoted T‐cell growth. Global mRNA profiling and pathway analysis showed activation of several signaling pathways important for lymphocyte proliferation and survival. These data provide new insights into the molecular involvement of Helios function in the leukemogenesis and phenotype of ATL cells, indicating that Helios deregulation is one of the novel molecular hallmarks of ATL.
A conceptual toolbox for designing CSCW applications

This paper presents a conceptual toolbox, developed to support the design of CSCW applications in a large Esprit project, EuroCODE. Here, several groups of designers work to investigate computer support for cooperative work in large use organizations, at the same time as they work to develop an open development platform for CSCW applications. The conceptual toolbox has been developed to support communication in and among these design groups, between designers and users and in future use of the open development platform. Rejecting the idea that one may design from a framework describing CSCW, the toolbox aims to support design by doing and help bridging between work with users, technical design, and insights gained from theoretical and empirical CSCW research.
Identification of two cDNAs encoding synaptic vesicle protein 2 (SV2)‐like proteins from epithelial tissues in the cat flea, Ctenocephalides felis

Two distinct cDNAs that appear to encode proteins in the synaptic vesicle‐2 (SV2) family were identified as expressed sequence tags from a Ctenocephalides felis hindgut and Malpighian tubule (HMT) cDNA library. To date, SV2 proteins have been described only in vertebrates, and have been detected only in synaptic vesicles in neuronal and endocrine tissues, where they are thought to regulate synaptic vesicle exocytosis. The cDNAs for the C. felis SV2‐like proteins SVLP‐1 and SVLP‐2 encode predicted full‐length proteins of 530 and 726 amino acids, respectively. Of characterized proteins, the SVLP protein sequences were most similar to rat SV2B. Northern blot analysis revealed that both mRNAs were up‐regulated in larval stages that feed and in adults after feeding, and were expressed primarily or exclusively in the HMT tissues in adult fleas. These results suggest that the flea SVLP‐1 and SVLP‐2 gene products may have roles that are specific for the HMT tissues, and may differ in function from vertebrate SV2 proteins.
Two distinct osteoblast-specific cis-acting elements control expression of a mouse osteocalcin gene

Osteoblasts are cells of mesodermal origin that play a pivotal role during bone growth and mineralization. The mechanisms governing osteoblast-specific gene expression are still unknown. To understand these mechanisms, we analyzed the cis-acting elements of mouse osteocalcin gene 2 (mOG2), the best-characterized osteoblast-specific gene, by DNA transfection experiments in osteoblastic and nonosteoblastic cell lines and by DNA-binding assays. 5' deletion analysis of an mOG2 promoter-luciferase chimeric gene showed that a region located between -147 and -34 contained most if not all of the regulatory elements required for osteoblast-specific expression. Three different binding sites, called A, B, and C, for factors present in nuclear extracts of osteoblasts were identified in this short promoter by DNase I footprint assays. In gel retardation assays, the A element, located between bp -64 and -47, bound a factor present only in nuclear extracts of osteoblastic cell lines and nonmineralizing primary osteoblasts. The B element, located between bp -110 and -83, bound a ubiquitously expressed factor. The C element, located between bp -146 and -132, bound a factor present only in nuclear extracts of osteoblastic cell lines and nonmineralizing and mineralizing primary osteoblasts. When cloned upstream of a minimum osteocalcin promoter or a heterologous promoter, multimers of the A element strongly increased the activities of these promoters in osteoblastic cell lines at two different stages of differentiation but in no other cell line; we named this element osteocalcin-specific element 1 (OSE1). Multimers of the C element increased the activities of these promoters predominantly in a differentiated osteoblastic cell line; we named this element OSE2. This study demonstrates that two distinct cis-acting elements are responsible for osteoblast expression of mOG2 and provides for the first time a functional characterization of osteoblast-specific cis-acting elements. We speculate that these two elements may be important at several stages of osteoblast differentiation.
Improved tolerability and quality of life with maintained efficacy using twice-daily low-dose interferon-alpha-2b: results of a randomized phase II trial of low-dose versus intermediate-dose interferon-alpha-2b in patients with metastatic renal cell carcinoma.

BACKGROUND In vivo data have shown a more potent antiangiogenic effect and a higher antitumor activity of low-dose interferon (IFN) given twice daily. In a randomized Phase II trial, the authors tested the hypothesis that twice-daily low-dose IFN is more effective than daily intermediate-dose IFN in patients with metastatic renal cell cancer (MRCC). METHODS A total of 118 patients (59 per arm) were randomly assigned to receive IFN at a dose of 0.5 million units (MU) given subcutaneously twice daily (IFN1) or IFN at a dose of 5 MU given subcutaneously daily (IFN5). The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR), overall survival (OS), toxicity, and quality of life (QOL). RESULTS There were no significant differences in either PFS or OS between IFN1 and IFN5 (median of 3.7 months and median of 3.4 months PFS, respectively; median of 25.5 months and median of 17.5 months OS, respectively). The RRs were identical in the 2 arms (6.7%; 95% confidence interval [95% CI], 1.8-16.5%). Two patients, 1 in each arm, remained in complete remission at the time of last follow-up, at 45+ and 38+ months from treatment. Thirty-two patients receiving IFN5 and 19 patients receiving IFN1 experienced Grade 3 or higher adverse events (graded using the National Cancer Institute Common Toxicity Criteria [version 2.0]) (P = .025). Eighteen patients receiving IFN5 and 4 patients receiving IFN1 had dose reductions (P = .002). There was a significant deterioration in QOL and an increase in depression associated with IFN5 but no change was noted with IFN1. CONCLUSIONS Compared with IFN5, IFN1 is neither more nor less effective but is less toxic, with a better reported QOL. These results may have implications for the design of combination regimens incorporating IFN with targeted agents.
Spatial Self‐Organization on Intertidal Mudflats through Biophysical Stress Divergence

In this study, we investigated the emergence of spatial self‐organized patterns on intertidal flats, resulting from the interaction between biological and geomorphological processes. Autocorrelation analysis of aerial photographs revealed that diatoms occur in regularly spaced patterns consisting of elevated hummocks alternating with water‐filled hollows. Hummocks were characterized by high diatom content and a high sediment erosion threshold, while both were low in hollows. These results highlight the interaction between diatom growth and sedimentary processes as a potential mechanism for spatial patterning. Several alternative mechanisms could be excluded as important mechanisms in the formation of spatial patterns. We developed a spatially explicit mathematical model that revealed that scale‐dependent interactions between sedimentation, diatom growth, and water redistribution explain the observed patterns. The model predicts that areas exhibiting spatially self‐organized patterns have increased sediment accretion and diatom biomass compared with areas lacking spatial patterns, a prediction confirmed by empirical evidence. Our study on intertidal mudflats provides a simple but clear‐cut example of how the interaction between biological and sedimentary processes, through the process of self‐organization, induces spatial patterns at a landscape level.
Finding home on Twitter

Eduard Campillo-Funollet applies a set of data analysis tools to the study of the concept of home on the social network Twitter. The main goals are to understand how the concept of home is used in Twitter, and also to show the power of data analysis techniques to study problems in humanities and social sciences. The study focuses on a dataset of tweets that contain the word home. After a preliminary exploration of the data, the chapter presents an analysis of the word frequency in the tweets, a sentiment analysis, and an application of a word sense disambiguation algorithm.
Plasticity for crushable granular materials via DEM

The mechanical behavior of crushable granular materials is characterized by strong non-linearity and irreversibility. In this paper, the incremental behavior of crushable granular soils is investigated by numerically simulating three dimensional stress probing experiments on Distinct Element models consisting of a random assembly of spheres. Particle breakage is permitted and the initial high stress condition ensures that crushing will occur along some of the loading directions. The results obtained show that particle crushing considered as an additional source of plastic mechanism induces a change in the direction of the plastic flow and that this direction change is independent of the incremental loading path. This result is independent of damping and the magnitude of plastic strains tends towards an asymptotic value as damping increases.
Bisphenol a exposure and the development of wheeze and lung function in children through age 5 years.

IMPORTANCE Bisphenol A (BPA), a prevalent endocrine-disrupting chemical, has been associated with wheezing in children, but few studies have examined its effect on lung function or wheeze in older children. OBJECTIVES To test whether BPA exposure is associated with lung function, with wheeze, and with pattern of wheeze in children during their first 5 years. DESIGN, SETTING, AND PARTICIPANTS A birth cohort study, enrolled during early pregnancy in the greater Cincinnati, Ohio, area among 398 mother-infant dyads. We collected maternal urine samples during pregnancy (at 16 and 26 weeks) and child urine samples annually to assess gestational and child BPA exposure. MAIN OUTCOMES AND MEASURES We assessed parent-reported wheeze every 6 months for 5 years and measured child forced expiratory volume in the first second of expiration (FEV1) at age 4 and 5 years. We evaluated associations of BPA exposure with respiratory outcomes, including FEV1, child wheeze, and wheeze phenotype. RESULTS Urinary BPA concentrations and FEV1 data were available for 208 children and urinary BPA concentrations and parent-reported wheeze data were available for 360 children. The mean maternal urinary BPA concentration ranged from 0.53 to 293.55 µg/g of creatinine. In multivariable analysis, every 10-fold increase in the mean maternal urinary BPA concentration was associated with a 14.2% (95% CI, -24.5% to -3.9%) decrease in the percentage predicted FEV1 at 4 years, but no association was found at 5 years. In multivariable analysis, every 10-fold increase in the mean maternal urinary BPA concentration was marginally associated with a 54.8% increase in the odds of wheezing (adjusted odds ratio, 1.55; 95% CI, 0.91-2.63). While the mean maternal urinary BPA concentration was not associated with wheeze phenotype, a 10-fold increase in the 16-week maternal urinary BPA concentration was associated with a 4.27-fold increase in the odds of persistent wheeze (adjusted odds ratio, 4.27; 95% CI, 1.37-13.30). Child urinary BPA concentrations were not associated with FEV1 or wheeze. CONCLUSIONS AND RELEVANCE These results provide evidence suggesting that prenatal but not postnatal exposure to BPA is associated with diminished lung function and the development of persistent wheeze in children.