Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Genome & Diseases: Review The human genome and understanding of common disease: present and future technologies

The study of candidate genes over the past three decades has yielded notable successes in com- mon-disease genetics. During this time, however, interpretation of genetic association studies has been hampered by the use of clinical cohorts of inadequate power and insufficient information on genetic varia- tion in candidate genes. The unavailability of high- throughput and low-cost genotyping technologies has also limited the scope of complex-disease genetic studies. More recently, however, the sequencing and characterization of variation within the human ge- nome has revolutionized genetic studies and enabled full genome-wide scans for genes associated with disease. The identification of disease-associated (caus- ative) genes has illuminated disease mechanisms. The translation of this knowledge into direct clinical benefit in diagnosis, prognosis and therapy for an individuals disease still remains a challenge. The sequencing of the human genome and identifica- tion of common inter-individual variation (polymor- phism) is revealing the complexity of our genetic makeup (1 - 4). It is clear that this variation plays a central role in the pathogenesis of common human disease. The existence of common disease-causing genetic variants is consistent with the idea that ancestral variations evolved in combination with an environment that provided a selective advantage to carriers of todays common polymorphisms. However, the presence of these variants in the modern gene pool can also result in less advantageous phenotypes. In the
Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development

Background: Epigenetic alterations are common in prostate cancer, yet how these modifications contribute to carcinogenesis is poorly understood. We investigated whether specific histone modifications are prognostic for prostate cancer relapse, and whether the expression of epigenetic genes is altered in prostate tumorigenesis. Methods: Global levels of histone H3 lysine-18 acetylation (H3K18Ac) and histone H3 lysine-4 dimethylation (H3K4diMe) were assessed immunohistochemically in a prostate cancer cohort of 279 cases. Epigenetic gene expression was investigated in silico by analysis of microarray data from 23 primary prostate cancers (8 with biochemical recurrence and 15 without) and 7 metastatic lesions. Results: H3K18Ac and H3K4diMe are independent predictors of relapse-free survival, with high global levels associated with a 1.71-fold (P < 0.0001) and 1.80-fold (P = 0.006) increased risk of tumor recurrence, respectively. High levels of both histone modifications were associated with a 3-fold increased risk of relapse (P < 0.0001). Epigenetic gene expression profiling identified a candidate gene signature (DNMT3A, MBD4, MLL2, MLL3, NSD1, and SRCAP), which significantly discriminated nonmalignant from prostate tumor tissue (P = 0.0063) in an independent cohort. Conclusions: This study has established the importance of histone modifications in predicting prostate cancer relapse and has identified an epigenetic gene signature associated with prostate tumorigenesis. Impact: Our findings suggest that targeting the epigenetic enzymes specifically involved in a particular solid tumor may be a more effective approach. Moreover, testing for aberrant expression of epigenetic genes such as those identified in this study may be beneficial in predicting individual patient response to epigenetic therapies. Cancer Epidemiol Biomarkers Prev; 19(10); 2611–22. ©2010 AACR.
Tissue-specific promoters for cancer gene therapy

Adenoviral cancer gene therapy approaches have resulted in promising recent results. Following only a decade of intense development, some of the crucial obstacles are now being overcome. Insufficient transduction has been the main limitation of earlier approaches. A new approach for increasing transduction of tumour cells is utilisation of replication-competent oncolytic agents, such as conditionally replicating adenoviruses (CRADs). The anti-tumour effect is caused by replication of the virus per se and, thus, replication must be restricted to tumour cells to protect normal tissues from damage. Tissue-specific promoters (TSPs) represent a powerful tool for decreasing the toxicity of cancer gene therapy to normal tissues and have previously been utilised for specific mutation compensation or delivery of prodrug-converting enzymes. However, TSPs can also be used for controlling crucial viral replication regulators and consequent restriction of replication to tumour cells. Initial clinical trials have demonstrated the safety and suggested efficacy for TSP-controlled CRADs as a novel approach for cancer gene therapy.
P3ARSEC: towards parallel patterns benchmarking

High-level parallel programming is a de-facto standard approach to develop parallel software with reduced time to development. High-level abstractions are provided by existing frameworks as pragma-based annotations in the source code, or through pre-built parallel patterns that recur frequently in parallel algorithms, and that can be easily instantiated by the programmer to add a structure to the development of parallel software. In this paper we focus on this second approach and we propose P3ARSEC, a benchmark suite for parallel pattern-based frameworks consisting of a representative subset of PARSEC applications. We analyse the programmability advantages and the potential performance penalty of using such high-level methodology with respect to hand-made parallelisations using low-level mechanisms. The results are obtained on the new Intel Knights Landing multicore, and show a significantly reduced code complexity with comparable performance.
Variation in Antibiotic Prescribing Across a Pediatric Primary Care Network.

BACKGROUND Outpatient respiratory tract infections are the most common reason for antibiotic prescribing to children. Although prior studies suggest that antibiotic overuse occurs, patient-specific data or data exploring the variability and determinants of variability across practices and practitioners is lacking. METHODS This study was conducted from a retrospective cohort of encounters to 25 diverse pediatric practices with 222 clinicians, from January 1 to December 31, 2009. Diagnoses, medications, comorbid conditions, antibiotic allergy, and demographic data were obtained from a shared electronic health record and validated by manual review. Practice-specific antibiotic prescription and acute respiratory tract infection diagnosis rates were calculated to assess across-practice differences after adjusting for patient demographics and clustering of encounters within clinicians. RESULTS A total of 102 102 (28%) of 399 793 acute visits by 208 015 patients resulted in antibiotic prescriptions. After adjusting for patient age, sex, race, and insurance type, and excluding encounters by patients with chronic conditions, antibiotic prescribing by practice ranged from 18% to 36% of acute visits, and the proportion of antibiotic prescriptions that were broad-spectrum ranged from 15% to 58% across practices, despite additional exclusion of patients with antibiotic allergies or prior antibiotic use. Diagnosis of (Dx) and broad-spectrum antibiotic prescribing (Broad) for acute otitis media (Dx: 8%-20%; Broad: 18%-60%), sinusitis (Dx: 0.5%-9%; Broad: 12%-78%), Streptococcal pharyngitis (Dx: 1.8%-6.4%; Broad: 2%-30%), and pneumonia (Dx: 0.4%-2%; Broad: 1%-70%) also varied by practice (P < 0.001 for all comparisons). CONCLUSIONS Antibiotic prescribing for common pediatric infections varied substantially across practices. This variability could not be explained by patient-specific factors. These data suggest the need for and provide high-impact targets for outpatient antimicrobial stewardship interventions.
Predictors of Expatriate Job Satisfaction --- An Example of Taiwanese Expatriates in Mainland China

Expatriates working in a foreign environment with very different political, cultural and economic conditions often face both job-related and personal problems, which may lead to expatriate dissatisfaction. Previous research suggests that if expatriates are not satisfied while on assignment, the motivation to perform well and/or to remain abroad for the specified length of times is diminished. As a result, this study tries to do investigations to Taiwanese expatriates in China to experiment if certain determinants (training, mentoring, repatriate positing, long-term career planning, environmental factors, and individual career management strategies) can lead to expatriate job satisfaction. The result of this study suggests that among corporate career development plans, training and long-term career planning can facilitate expatriate job satisfaction, while mentoring and repatriate positing have no significant influence on job satisfaction. Besides, environmental factors and individual career management strategies both have significant positive effect on job satisfaction. This gives multinational companies (MNCs) some inspirations: MNCs should do some investigations to previous expatriates to figure out the problems they’ve encountered and design corresponding training programs for new expatriates. MNCs should select expatriates with positive attitudes towards expatriate assignments or train their expatriates to become more problem-focused. MNCs should help expatriates plan their future career paths. MNCs should design sound mentoring and repatriate positing policies for their expatriates.MNCs should make the environments surrounding expatriates become as benevolent as possible.
The Resonating Valence Bond State in La2CuO4 and Superconductivity

The oxide superconductors, particularly those recently discovered that are based on La2CuO4, have a set of peculiarities that suggest a common, unique mechanism: they tend in every case to occur near a metal-insulator transition into an odd-electron insulator with peculiar magnetic properties. This insulating phase is proposed to be the long-sought "resonating-valence-bond" state or "quantum spin liquid" hypothesized in 1973. This insulating magnetic phase is favored by low spin, low dimensionality, and magnetic frustration. The preexisting magnetic singlet pairs of the insulating state become charged superconducting pairs when the insulator is doped sufficiently strongly. The mechanism for superconductivity is hence predominantly electronic and magnetic, although weak phonon interactions may favor the state. Many unusual properties are predicted, especially of the insulating state.
Chemically Driven Motility of Brownian Particles.

A simple model is devised to show that an enzymatic Brownian particle in a static electric field can undergo directional movement when coupled with a nonequilibriumchemical reaction which the particle catalyzes, if at least one of the intermediate states of the catalytic cycle is charged. The direction of the movement depends not only on the asymmetry of the electric field, but also on the direction of the chemical reaction and the mechanism of the catalytic cycle. The Brownian particle can also move against an external load and thus do mechanical work. This study suggests that enzyme molecules could be separated based on their enzymatic activities. The formalism developed in this paper can be extended and applied to biological motors. [S0031-9007(96)00487-5]
catena-Poly[zinc-tris(μ-dimethylcarbamato-κ2 O:O′)-zinc-μ-(2-phenylbenzimidazolido-κ2 N:N′]

The crystal structure of the title compound, [Zn2(C13H9N2)(C3H6NO2)3]n, displays a long chiral chain. This is composed of zinc-dimer clusters capped by dimethylcarbamate ligands, which lie on crystallographic twofold rotation axes and are polymerically linked in one dimension by 2-phenylbenzimidadole (2–PBImi) organic ligands. The two Zn2+ ions defining the dimetal cluster are crystallographically independent, but display very similar coordination modes and tetrahedral geometry. As such, each Zn2+ ion is coordinated on one side by the N-donor imidazole linker, while the other three available coordination sites are fully occupied by the O atoms from the capping dimethylcarbamates. The chirality of the chain extends along the c axis, generating a rather long 52.470 (11) Å cell axis. Interestingly, the chiral material crystallizes from completely achiral precursors. A twofold axis and 31 screw axis serve to generate the long asymmetric unit.
Development and Examination of the Five-Factor Obsessive-Compulsive Inventory–Short Form

The Five-Factor Obsessive-Compulsive Inventory (FFOCI) is an assessment of obsessive-compulsive personality disorder (OCPD) that is based on the conceptual framework of the five-factor model (FFM) of personality. The FFOCI has 12 subscales that assess those five-factor model facets relevant to the description of OCPD. Research has suggested that the FFOCI scores relate robustly to existing measures of OCPD and relevant scales from general personality inventories. Nonetheless, the FFOCI’s length—120 items—may limit its clinical utility. This study derived a 48-item FFOCI–Short Form (FFOCI-SF) from the original measure using item response theory methods. The FFOCI-SF scales successfully recreated the nomological network of the original measure and improved discriminant validity relative to the long form. These results support the use of the FFOCI-SF as a briefer measure of the lower-order traits associated with OCPD.
Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of ESMO.

BACKGROUND The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last 4 years. The objectives of this international consensus meeting were to describe the optimal management procedures for patients with GIST in localized and advanced stages, as well as research issues for the future. MATERIALS AND METHODS A panel of experts from six specialties, including pathology, molecular biology, imaging, surgery, medical oncology and methodologists for clinical practice guidelines from different European and extra European sarcoma societies were invited to a 2-day workshop. Several questions were selected by the organizing committee prior to the conference. Selected panelists reviewed the current levels of evidence for each point, and presented their conclusions during the meeting. These proposals were discussed, and consensus points were identified and categorized according to the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers and National Comprehensive Cancer Network (NCCN). RESULTS Thirty-two consensus points were identified, most from categories 2A of the NCCN and B2 of the SOR. Among these, the standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is an optional diagnostic procedure for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. The optimal criteria for tumor response to imatinib remain to be delineated, and should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield Units) on computed tomography and metabolic activity (i.e. reduction of FDG uptake on positron emission tomography). In a substantial proportion of patients, stable disease and even increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. Metastasis resection is an experimental procedure. CONCLUSIONS Consensus points in clinical management of GIST as well as questions for future clinical trials were identified during this consensus conference on GIST management.
Effect of endoscopic sinus surgery on pulmonary function and microbial pathogens in a pediatric population with cystic fibrosis.

OBJECTIVE To assess whether improvements in pulmonary function and microbial pathogenic findings can be achieved by endoscopic sinus surgery in a pediatric population with cystic fibrosis. DESIGN Retrospective medical record review. SETTING Academic research. PATIENTS Forty-one patients with cystic fibrosis who had undergone endoscopic sinus surgery at a single tertiary academic pediatric otolaryngology practice. MAIN OUTCOME MEASURES Changes in pulmonary function test values or respiratory tract microbial pathogens after endoscopic sinus surgery were examined. RESULTS Endoscopic sinus surgery did not improve pulmonary function test results in this population. Examination of respiratory tract microbial colonization showed that endoscopic sinus surgery did not affect microbial pathogens. The most common organisms isolated were Staphylococcus aureus and Pseudomonas aeruginosa. CONCLUSION The lack of effect of endoscopic sinus surgery on pulmonary function test results and respiratory tract microbial pathogens in our study highlights the need for prospective assessments of postoperative quality-of-life improvement and of adjunct medical therapy efficacy.
Foreigners in the Confederacy

The Confederate armies included in their ranks a remarkable range of nationalities - among them Germans, Irish, Italians, French, Poles, Mexicans, Cubans, Hungarians, Russians, Swedes, Danes, and Chinese. Covering the complete story of the activities of the foreigners in the Confederacy - in both military and civil service - this book recognizes their many contributions to the cause of the South. First published in 1940, it remains the only work on the subject.
Lapita Colonization across the Near/Remote Oceania Boundary

The Lapita colonization of Remote Oceania involved rapid expansion from New Guinea across one-tenth of the circumference of the earth. Implicit in most discussions of this phenomenon is a standard wave-of-advance model founded on demographic growth and the economic advantage provided by food production. The Lapita movement is also routinely embedded within a much larger narrative of the expansion of Austronesian languages and peoples out of Southeast Asia into Island Melanesia and ultimately east through East Polynesia. Although this simple narrative is very attractive, as more data become available, the details of segments of the “Austronesian” expansion require revision in order to reconcile the data from archaeology, linguistics, and biology. This paper looks closely at recent data on the Lapita portion of the “Austronesian” expansion and concludes that it is best explained as a leapfrog rather than a wave-of-advance movement out of New Guinea into Remote Oceania. This has important implications for those interested in modeling linguistic and biological variation in the region and highlights the potential importance of historical accident over process in our understanding of culture history.
Nascent helix in the multiphosphorylated peptide αS2‐casein(2–20)

Sequence‐specific nuclear magnetic resonance (NMR) assignments have been determined for the peptide αS2‐CN(2–20) containing the multiphosphorylated motif‐8Ser(P)‐Ser(P)‐Ser(P)‐Glu‐Glu12‐ in the presence of molar excess Ca2+. The secondary structure of the peptide was characterized by sequential (i,i + 1), medium‐range (i,i + 2/3/4) nOes and Hα chemical shifts. Molecular modelling of the peptide based on these constraints suggests a nascent helix for residues Ser(P)9 to Glu12. The spectral data for αS2‐CN(2–20) were compared with those of other casein phosphopeptides β‐CN(1–25) and αS1‐CN(59–79) that also contain the multiphosphorylated motif. This comparison revealed a similar pattern of secondary amide chemical shifts in the multiphosphorylated motif. However, the patterns of medium‐range nOe connectivities in the three peptides suggests they have distinctly different conformations in the presence of Ca2+ despite having a high degree of sequential similarity. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.
Review of successful treatment for Helicobacter species in laboratory mice

Three variations of the amoxycillin-based triple therapy (amoxycillin, metronidazole and bismuth) were administered in the diet, by oral gavage or in the diet in conjunction with cross-fostering on to Helicobacter-free foster mothers to mice naturally infected with H. hepaticus and/or H. bilis. The presence of Helicobacter species was determined by polymerase chain reaction (PCR) analysis of faecal pellets. Helicobacter infection was eliminated in 50% of strains of mice treated by oral gavage; 57% of strains of mice treated by medicated diet alone and 100% of strains of mice treated with the medicated diet in conjunction with cross-fostering on to Helicobacter-free foster mothers. Eight strains of mice were successfully treated for Helicobacter infection over a two-year period. The mouse colony has been maintained Helicobacter free, as determined by PCR analysis and has remained off treatment from December 2002 to March 2005.
The V Protein of Simian Virus 5 Inhibits Interferon Signalling by Targeting STAT1 for Proteasome-Mediated Degradation

ABSTRACT To replicate in vivo, viruses must circumvent cellular antiviral defense mechanisms, including those induced by the interferons (IFNs). Here we demonstrate that simian virus 5 (SV5) blocks IFN signalling in human cells by inhibiting the formation of the IFN-stimulated gene factor 3 and gamma-activated factor transcription complexes that are involved in activating IFN-α/β- and IFN-γ-responsive genes, respectively. SV5 inhibits the formation of these complexes by specifically targeting STAT1, a component common to both transcription complexes, for proteasome-mediated degradation. Expression of the SV5 structural protein V, in the absence of other virus proteins, also inhibited IFN signalling and induced the degradation of STAT1. Following infection with SV5, STAT1 was degraded in the absence of virus protein synthesis and remained undetectable for up to 4 days postinfection. Furthermore, STAT1 was also degraded in IFN-pretreated cells, even though the cells were in an antiviral state. Since pretreatment of cells with IFN delayed but did not prevent virus replication and protein synthesis, these observations suggest that following infection of IFN-pretreated cells, SV5 remains viable within the cells until they eventually go out of the antiviral state.
The effect of basic fibroblast growth factor and adipose tissue-derived mesenchymal stem cells on wound healing, epithelization and angiogenesis in a tracheal resection and end-to-end anastomosis rat model

1Department of Thoracic Surgery, Medical Faculty of Kirikkale University, Kirikkale, Turkey 2Department of Biology, Hacettepe University, Faculty of Science, Ankara, Turkey 3Department of Pathology, Medical Faculty of Baskent University, Ankara, Turkey 4Department of Internal Medicine, Kirikkale University, Faculty of Veterinary Medicine, Kirikkale, Turkey 5Department of Cardiovascular Surgery, Medical Faculty of Kirikkale University, Kirikkale, Turkey