Miracle-dz/UniFAR-FTUs huggingface dataset:
Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data

A variety of models have been proposed to explain regions of recurrent somatic copy number alteration (SCNA) in human cancer. Our study employs Whole Genome DNA Sequence (WGS) data from tumor samples (n = 103) to comprehensively assess the role of the Knudson two hit genetic model in SCNA generation in prostate cancer. 64 recurrent regions of loss and gain were detected, of which 28 were novel, including regions of loss with more than 15% frequency at Chr4p15.2-p15.1 (15.53%), Chr6q27 (16.50%) and Chr18q12.3 (17.48%). Comprehensive mutation screens of genes, lincRNA encoding sequences, control regions and conserved domains within SCNAs demonstrated that a two-hit genetic model was supported in only a minor proportion of recurrent SCNA losses examined (15/40). We found that recurrent breakpoints and regions of inversion often occur within Knudson model SCNAs, leading to the identification of ZNF292 as a target gene for the deletion at 6q14.3-q15 and NKX3.1 as a two-hit target at 8p21.3-p21.2. The importance of alterations of lincRNA sequences was illustrated by the identification of a novel mutational hotspot at the KCCAT42, FENDRR, CAT1886 and STCAT2 loci at the 16q23.1-q24.3 loss. Our data confirm that the burden of SCNAs is predictive of biochemical recurrence, define nine individual regions that are associated with relapse, and highlight the possible importance of ion channel and G-protein coupled-receptor (GPCR) pathways in cancer development. We concluded that a two-hit genetic model accounts for about one third of SCNA indicating that mechanisms, such haploinsufficiency and epigenetic inactivation, account for the remaining SCNA losses.
Cross-Feedback Output-Current-Sharing Control for Input-Series-Output-Parallel Modular DC–DC Converters

The input-series-output-parallel (ISOP) connection, consisting of multiple modular dc/dc converters connected in series at the input and parallel at the output, is a good alternative to be used under high-voltage input applications with low-voltage-rating switches. A novel output-current-sharing scheme, consisting of one output-voltage loop and individual output-currents loops, is proposed in this paper. The output-voltage loop provides a common reference for all individual current loops in which the current feedback for an individual converter is not its own, but the sum of all the remaining output currents. The stability and operation principles of the proposed scheme are analyzed. A three-module ISOP system is taken as an example to show small-signal analysis and loop-gain design with the proposed scheme. Both excellent sharing of the input voltage and the load current can be achieved with the proposed scheme. Besides, the output-voltage-regulation loop design is simplified and the overall reliability can be enhanced due to the inherent fault-tolerant and hot-swapping feature of the scheme. The performance of the proposed control strategy is verified by experimental results of a 200-W ISOP system consisting of three two-transistor forward dc/dc modules.
Telomere length is reflected by plumage coloration and predicts seasonal reproductive success in the barn swallow

Individuals differ in realized fitness but the genetic/phenotypic traits that underpin such variation are often unknown. Telomere dynamics may be a major source of variation in fitness traits because physiological telomere shortening depends on environmental and genetic factors and may impair individual performance. Here, we showed that, in a population of a socially monogamous, biparental passerine bird, the barn swallow (Hirundo rustica), breeding in northern Italy, telomere length (TL) of both adult males and females positively correlated with seasonal reproductive and fledging success, as expected because long telomeres are supposed to boost performance. Telomere length was correlated with sexually dimorphic coloration in both sexes, showing for the first time in any species that coloration reliably reflects TL and may mediate mutual mate choice, leading to the observed positive assortative mating for TL in the barn swallow. Thus, TL appears to be associated with variation in a major fitness trait and may be an ultimate target of mate choice, as individuals of both sexes can use coloration to adaptively choose high‐quality mates that possess long telomeres.
Analysis of Perceptions of the 1997 Louisiana Legislature Toward the Louisiana Cooperative Extension Service.

The study determined the perceptions that the members of the 1997 Louisiana Legislature held o f the Louisiana Cooperative Extension Service (LCES) and identified factors that affected the perceptions. The factors included in the study were: familiarity with LCES programs, perception o f effectiveness, sources o f LCES information, and participation in LCES programs. The study also determined the association o f selected characteristics with Legislators' perceptions. Of the 144 legislators contacted, 109 surveys (76%) were returned. Descriptive statistics were used to describe the personal characteristics of the legislators and correlation coefficients were calculated. Stepwise multiple regression at the . 05 level was used to develop a model which explained the legislators' perception o f LCES. Findings indicated that legislators were familiar with LCES, with the 4-H program receiving the highest familiarity. The agriculture and 4-H programs were perceived as very effective by the legislators. The legislators indicated that printed information, personal contacts, newsletters and newspaper articles provided moderate exposure to LCES. A majority of the legislators had attended at least one 4-H youth development activity. Rural legislators were more familiar with LCES, were more likely to be exposed to LCES information sources, perceived LCES as effective, and participated more in LCES activities than urban legislators. Little correlation existed between age o f legislators, their years of service in the legislature and familiarity, participation, xi Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. perception and participation. In the regression model, party affiliation of the legislator was the best predictor o f familiarity and explained 18% of the variance. Age was the best predictor of legislators' participation in LCES programs; considered alone, this variable explained 6% o f the variance. Agriculture Committee membership was the best predictor of perception of the effectiveness of LCES programs and explained 12% of the variance. Agriculture Committee membership also was the best predictor of legislators' exposure to LCES information sources, explaining 12% of the variance. Recommendations were that programs be designed for strengthening the image of the LCES. An effort must be made to help both rural and urban legislators understand the mission and programs of LCES, with special emphasis on urban populations.
Three Decades of IPO Markets in Canada: Evolution, Risk and Return

In Canada, initial public offerings (IPOs) have decreased sharply over the past twenty years, inducing potentially substantial negative effects on the economy. The reasons for this decrease are controversial. To contribute to the debate, we analyze the Canadian IPO market over three decades (1986-2016). First we illustrate its specificities using IPOs on the main and the venture stock exchanges and using other junior markets a benchmark. We discuss the evolution of the IPOs, which differs considerably between natural resource and non-natural resource firms. We then provide empirical evidence based on 2,145 Canadian IPOs. On average, these IPOs generate three-year negative abnormal returns, and more than 70% report negative abnormal returns. Large issuers reporting profits constitute the only subsample that provides fair returns, but they account for less than 5% of IPOs. We observe a high level of skewness of abnormal returns, consistent with the behavioral finance proposition that investors are often unduly optimistic when valuing lottery stocks. The lemon market characteristics of the Canadian IPO market can probably explain why it is vanishing.
A method for stabilizing RNA for transfection that allows control of expression duration

RNA transfection methods have not proven to be as popular as DNA methods due to the highly transient nature of the RNA inside the cell. However, there are many advantages in using RNA for gene over‐expression, such as the rapidity of expression, the ability to express in all cell types without the need for cell‐type‐specific promoters, and the ability to analyze the effects of gene over‐expression in a transient manner. Therefore, we have developed a method (StabiLizingUtr: SLU) to stabilize the RNA for varying durations, using specific sequences from the 3′UTR of the Venezuelan equine encephalitis virus (VEEV). We have designed a plasmid for cloning genes upstream from repeated stabilizing sequences to generate mRNA with one or more VEEV‐stabilizing sequence motifs. We demonstrate this method in several cell and tissue types, including the mammalian cochlea, a tissue that has been difficult to transfect with other methods. Developmental Dynamics 239:2034–2010, 2010. © 2010 Wiley‐Liss, Inc.
Baseline Serum β-carotene Concentration and Mortality among Long-Term Asbestos-Exposed Insulators

Background: Although interventional trials demonstrated that moderate-dose β-carotene supplementation increases lung cancer mortality in smokers and asbestos-exposed workers, differences in serum concentrations in absence of supplementation have not been studied in asbestos-exposed workers. Methods: A mortality analysis was performed to assess the relationship of nonsupplemented serum β-carotene to all-cause and cancer mortalities using 1981 to 1983 serum β-carotene concentration measurements from 2,646 U.S. white male insulators (mean age, 57.7 years). Multivariable-adjusted Cox proportional hazard models that included terms for age, duration of asbestos exposure, smoking, season, and region were fitted to estimate mortality HRs and 95% confidence intervals (CI) according to serum β-carotene concentrations. Results: Median follow-up was 12.8 years and 984 (33.8%) subjects died during the follow-up period, including 415 deaths from overall cancer and 219 deaths from lung cancer. The overall mortality HR for a serum β-carotene increase of 10 μg/dL was 0.97 (95% CI, 0.96–0.99). Compared with the lowest quartile, HRs were 0.90 (95% CI, 0.76–1.07) for the second (38–65 μg/dL), 0.80 (95% CI, 0.67–0.96) for the third (66–104 μg/dL), and 0.63 (95% CI, 0.51–0.77) for the highest serum β-carotene quartile (≥105 μg/dL). There was no association between serum β-carotene and overall cancer mortality (HR, 1.00; 95% CI, 0.97–1.02) or lung cancer mortality (HR, 0.99; 95% CI, 0.96–1.02). Conclusions: Higher nonsupplemented serum β-carotene concentrations were negatively associated with all-cause mortality among asbestos-exposed individuals. Impact: Serum β-carotene can be a marker of one or more determinants of reduced mortality in asbestos-exposed workers. Cancer Epidemiol Biomarkers Prev; 24(3); 555–60. ©2014 AACR.
On the reaction of d‐amino acid oxidase with dioxygen: O2 diffusion pathways and enhancement of reactivity

Evidence is accumulating that oxygen access in proteins is guided and controlled. We also have recently described channels that might allow access of oxygen to pockets at the active site of the flavoprotein d‐amino acid oxidase (DAAO) that have a high affinity for dioxygen and are in close proximity to the flavin. With the goal of enhancing the reactivity of DAAO with oxygen, we have performed site‐saturation mutagenesis at three positions that flank the putative oxygen channels and high‐affinity sites. The most interesting variants at positions 50, 201 and 225 were identified by a screening procedure at low oxygen concentration. The biochemical properties of these variants have been studied and compared with those of wild‐type DAAO, with emphasis on the reactivity of the reduced enzyme species with dioxygen. The substitutions at positions 50 and 225 do not enhance this reaction, but mainly affect the protein conformation and stability. However, the T201L variant shows an up to a threefold increase in the rate constant for reaction of O2 with reduced flavin, together with a fivefold decrease in the Km for dioxygen. This effect was not observed when a valine is located at position 201, and is thus attributed to a specific alteration in the micro‐environment of one high‐affinity site for dioxygen (site B) close to the flavin that plays an important role in the storage of oxygen. The increase in O2 reactivity observed for T201L DAAO is of great interest for designing new flavoenzymes for biotechnological applications.
Human osteoclasts, not osteoblasts, deposit osteopontin onto resorption surfaces: An in vitro and ex vivo study of remodeling bone

Osteopontin is a phosphorylated glycoprotein believed to be secreted by osteoblasts and deposited into the bone matrix to facilitate osteoclast adhesion or to initiate osteoid mineralization. Previously we have presented contradictory evidence that osteoclasts express osteopontin mRNA in human remodeling bone. The aim of this study was to ascertain whether osteoclasts synthesize and deposit osteopontin in resorption lacunae. We characterized expression of osteopontin mRNA and protein expression in both intramembranous and endochondral ossification, as well as remodeling bone, in the human osteophyte. Osteopontin mRNA was expressed in osteoclasts with tartrate‐resistant acid phosphatase (TRAP) positivity within resorption lacunae. The osteoclasts and immediate resorption surfaces also expressed osteopontin. However, osteopontin mRNA and protein were weak (transient) or undetectable in osteoblasts at adjacent bone formation sites; no osteopontin expression was observed in the osteoid, although occasional reactivity was observed in osteocytes and the mineral‐osteoid interface. In contrast, osteopontin was highly expressed in the osteoblasts and matrix of woven bone during intramembranous and endochondral ossification. The matrix expression correlated with mineralization; however, in some instances osteopontin deposition was observed prior to mineralization. Similarly, osteopontin expression was evident in cartilage matrix, solely at foci of mineralization. Chondroclasts expressed osteopontin mRNA and protein; the surfaces of resorbed calcified cartilage also expressed osteopontin. Abnormal, unmineralized matrices apparently lacked deposited osteopontin, but were nevertheless resorbed by osteoclasts; the osteoclasts and resorbed surfaces expressed no osteopontin protein. That osteoclasts are responsible for the deposition of osteopontin was confirmed in vitro, whereby resorption pits in whale dentine and bovine bone slices, produced by isolated human osteoclasts, contained deposited osteopontin. Osteopontin may facilitate the adhesion (or detachment) of the osteoclast to the bone surface. Alternatively, the possibility that osteopontin may act as a postresorptive signal to recruit osteoblasts, or to polarize and direct the mineralization of the formed osteoid, is discussed.
Effect of Individualized Exercise Training Combined with Diet Restriction on Inflammatory Markers and IGF-1/IGFBP-3 in Obese Children

Aims: The present study was designed to examine the possible changes in body composition, insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3) and inflammatory markers of obese children in response to a 2-month program of exercise training combined with dietary restriction. Methods: Twenty-eight obese children (age 13.2 ± 0.7 years, body mass index 30.9 ± 1.3) were randomly assigned to a diet/training group or a control group and were tested two times: once before and once at the end of the experimental period. They performed a progressive cycle ergometer test at each visit. Substrate oxidation was evaluated by indirect calorimetry. Training was individualized at the point when fat oxidation was maximal (Lipoxmax). Results: Diet/training induced a significant decrease in body weight and body fat (after vs. before, p < 0.01). Plasma concentrations of IGF-1, IGFBP-3 and inflammatory markers were significantly decreased after the completion of the program. The diet/training program resulted in an increase in VO2maxACSM (24.6 ± 2.5 to 33.1 ± 3.1 ml/min/kg, p < 0.001) at the end of the intervention period. Conclu- sion: These data suggest that in the presence of weight loss, exercise training improves inflammatory markers and IGF-1 and IGFBP-3 levels in obese children.
Objective biomarkers of balance and gait for Parkinson's disease using body‐worn sensors

Balance and gait impairments characterize the progression of Parkinson's disease (PD), predict the risk of falling, and are important contributors to reduced quality of life. Advances in technology of small, body‐worn, inertial sensors have made it possible to develop quick, objective measures of balance and gait impairments in the clinic for research trials and clinical practice. Objective balance and gait metrics may eventually provide useful biomarkers for PD. In fact, objective balance and gait measures are already being used as surrogate endpoints for demonstrating clinical efficacy of new treatments, in place of counting falls from diaries, using stop‐watch measures of gait speed, or clinical balance rating scales. This review summarizes the types of objective measures available from body‐worn sensors. The metrics are organized based on the neural control system for mobility affected by PD: postural stability in stance, postural responses, gait initiation, gait (temporal‐spatial lower and upper body coordination and dynamic equilibrium), postural transitions, and freezing of gait. However, the explosion of metrics derived by wearable sensors during prescribed balance and gait tasks, which are abnormal in individuals with PD, do not yet qualify as behavioral biomarkers, because many balance and gait impairments observed in PD are not specific to the disease, nor have they been related to specific pathophysiologic biomarkers. In the future, the most useful balance and gait biomarkers for PD will be those that are sensitive and specific for early PD and are related to the underlying disease process. © 2013 International Parkinson and Movement Disorder Society
Factors Associated With Opinions About Hospice Among Older Adults

Attitudes and opinions about end-of-life care among older adults are understudied. Using survey data from the American Association of Retired Persons (AARP) membership in Florida (N = 2714), this study identified predictors of opinions about hospice (OAH) among older adults. Relationships between race/ethnicity and attitudes were also examined. Results showed race of the respondent was the strongest predictor of one’s OAH. Predictors of positive opinions of hospice included being of Caucasian race, non-Hispanic ethnicity, better health, greater familiarity with hospice, a high importance of pain control, the importance of fulfilling personal goals, a desire to have health-care professionals involved in one’s care, and having engaged in advance care planning. These findings suggest a need for greater attention to culture-based elements in future research and practice.
How International Is Political Science? Patterns of Submission and Publication in the American Political Science Review

ABSTRACT How international in scope is publishing in political science? Previous studies have shown that the top journals primarily publish work by scholars from the United States and, to a lesser extent, other global-north countries. However, these studies used published content and could not evaluate the impact of the review process on the relative absence of international scholars in journals. This article evaluates patterns of submission and publication by US and international scholars for the American Political Science Review—one of the most selective peer-reviewed journals in the discipline. We found that scholars from the United States and other global-north countries are published approximately in proportion to submissions but that global-south scholars fare less well. We also found that scholars affiliated with prestigious universities are overrepresented, irrespective of geographic location. The article concludes with observations about the implications of these findings for efforts to internationalize the discipline.
Liberal peace and peacebuilding: global and local debates in the context of Sri Lanka

This paper examines the key global debates on liberal peace and peacebuilding and their nexus with the Sri Lankan conflict, the efforts to resolve the conflict and the ensuing local discourses. The end of the cold war heralded the possibility of a liberal world order. This triumph of the liberal order underlined a normative assumption of “the end of history”, not as a static closure, but as embodying an ideology with the potential for delineating the optimal form of governance for a state, its economy and citizens1. Since the end of the cold-war, liberal peace has become the main policy framework that has been used by the International Community (IC) to engage with and intervene in conflict ridden states as a means for creating global peace by stabilising states and strengthening global markets2. However, the liberal peace thesis and the attendant liberal peacebuilding interventionist frameworks for local and global peace have spurned a critical discourse that questions the validity of the thesis and the effectiveness of its policy and practice outcomes. Sri Lanka mirrors the global debates and policy impact of the ideological framework of the global thesis, as it has a history of liberal governance (traceable to the 19th century) and liberal peacebuilding (traceable to the 20th century).
Association between vitamin D receptor, CCR5, TNF-alpha and TNF-beta gene polymorphisms and HBV infection and severity of liver disease.

BACKGROUND/AIMS 1,25-dihydroxyvitamin-D is involved in immunomodulation. Expression of vitamin-D receptors in hepatocytes suggests its role in hepatocellular injury. We studied the association of single nucleotide polymorphisms in genes involved in immunoregulatory functions of vitamin-D with susceptibility, severity and persistence of HBV infection. METHODS Five polymorphisms in VDR, CCR5, TNF-alpha and TNF-beta were studied in 214 chronic hepatitis B patients and 408 controls. Clinical parameters were compared between mild or severe liver disease patients. RESULTS The frequency of heterozygosity of CCR5Delta32 was higher in chronic hepatitis B patients than controls (4.2 vs 0.73%, P=0.005). Frequency of VDR Apa1 a/a and TNF-beta A/A was higher in severe compared with mild liver disease based on HAI (19.3 vs 5.4%, P=0.003 and 18.1 vs 3.8%, P=0.001, respectively) and fibrosis score (23.7 vs 3.6%, P<0.001 and 18.1 vs 4.4%, P=0.002, respectively). The frequency of VDR a/a allele was also higher in patients with higher HBV DNA (11 vs 2.6%, P=0.002). Apa1 and Taq1 markers in VDR are in linkage-disequilibrium and 'at'haplotype is associated with severe liver disease. CONCLUSIONS CCR5Delta32 heterozygosity was associated with susceptibility and VDR a/a, TNF-beta A/A with severity of HBV-related liver disease and VDR a/a allele with higher viral load. These results affirm an important role of immunogenetic factors in the outcome of chronic HBV infection.