Miracle-dz/UniFAR-FTUs huggingface dataset:
Catechol O-methyltransferase pharmacogenomics: human liver genotype–phenotype correlation and proximal promoter studies

Objectives Catechol O-methyltransferase (COMT) is expressed as both soluble (S) and membrane-bound (MB) isoforms, with S-COMT predominantly expressed in the liver. A common nonsynonymous single nucleotide polymorphism (SNP), 472G>A (108/158Val>Met, S/MB), has been associated with variation in levels of COMT enzyme activity and thermal stability. We set out to test the hypothesis that additional COMT polymorphisms might also be associated with phenotypic variation. Methods We phenotyped 268 liver biopsy samples for S-COMT activity and thermal stability, resequenced a portion of the gene that had not been resequenced earlier, and genotyped DNA from these same samples for 16 COMT polymorphisms. Results There was a significant association between the two COMT phenotypes and genotype at the codon 108 SNP. A haplotype-based approach was then used to assess the possible association of other polymorphisms with phenotype. Specifically, the codon 108 SNP explained 20.4% of variance in enzyme activity (P<10−6), and 59% of variance in thermal stability (P<10−6). Haplotypes that included SNPs at cDNA nucleotides 408 and 472 explained additional variance in enzyme activity (up to 24.4%), and the addition to the haplotype of a SNP at intron 2 (51) explained a total of 27.5% of the variance. However, no SNPs beyond that at the nucleotide 472G>A polymorphism were associated with variation in thermal stability. We also observed a three-fold variation in the ability of reporter gene constructs for ‘proximal promoter’ haplotypes to drive transcription. Conclusion The common COMT 108Val>Met polymorphism is associated with human liver S-COMT activity and thermal stability, but additional COMT SNPs also contribute to variation in activity.
Risky Business: Medical Discourse, Breast Cancer, and Narrative

This study explores the construction of risk and patient identity in medical discourse directed toward women with breast cancer. Eleven documents produced by the National Cancer Institute on the topic of breast cancer are studied using narrative analysis. A distinct patient narrative presents all women as at risk for breast cancer and creates an idealized patient identity that serves a prescriptive function for women. The narrative constructs an early-cancer experience where the patient is treatable and cancer is cured or controlled. There are no significant changes in the narrative after time.
Surface electromyography and acceleration based Sign Language Recognition using Hidden Conditional Random Fields

Sign Language Recognition has numerous applications, such as building a platform for the communication between the deaf and the hearing world. In this paper, Hidden Conditional Random Field (HCRF), a novel probabilistic model which has already been used in the area of speech and image recognition, was proposed for Sign Language Recognition (SLR) based on surface electromyography (sEMG) and acceleration (ACC) signals. Because of its latent and discriminative property, HCRF, as a branch of CRF models, was selected for this SLR task. In the proposed method, after the periods of data acquisition, data segmentation, feature extraction, and preliminary recognition on the decision-tree level, HCRF was utilized in the bottom layer to classify an observation sequence into a specific class. Experiments conducted on five subjects and 120 high-frequency used Chinese sign language subwords obtained 91.51% averaged recognition accuracy. This result demonstrated that HCRF is feasible and effective for the sEMG and ACC based Sign Language Recognition.
In Vivo HIV-1 Rev Multimerization in the Nucleolus and Cytoplasm Identified by Fluorescence Resonance Energy Transfer*

Nuclear export of intron-containing human immunodeficiency virus type 1 RNA is mediated by the viral Rev protein. Rev is a nucleocytoplasmic transport protein that directly binds to its cis-acting Rev-responsive element RNA. Rev function depends on its ability to multimerize. The in vivo dynamics and the subcellular dependence of this process are still largely unexplored. To visualize and quantitatively analyze the mechanism of Rev multimeric assembly in live cells, we used high resolution in vivo fluorescence resonance energy transfer (FRET) and fluorescence recovery after photobleaching. By using two different dynamic FRET approaches (acceptor photobleaching and donor bleaching time measurements), we observed a strong Rev-Rev interaction in the nucleoli of living cells. Most interestingly, we could also detect Rev multimerization in the cytoplasm; however, FRET efficiency in the cytoplasm was significantly lower than in the nucleolus. By using fluorescence recovery after photobleaching, we investigated the mobility of Rev within the nucleolus. Mathematical modeling of the fluorescence recovery after photobleaching recoveries enabled us to extract relative association and dissociation constants and the diffusion coefficient of Rev in the nucleolus. Our results show that Rev multimerizes in the nucleolus of living cells, suggesting an important role of the nucleolus in nucleocytoplasmic transport.
Memory functioning in children and adolescents with autism.

OBJECTIVE Memory functioning in children and adolescents ages 5-19 with autism (n = 50) and typically developing controls (n = 36) was assessed using a clinical assessment battery, the Test of Memory and Learning (TOMAL). METHOD Participant groups were statistically comparable in age, nonverbal IQ, handedness, and head circumference, and were administered the TOMAL. RESULTS Test performance on the TOMAL demonstrated broad differences in memory functioning in the autism group, across multiple task formats, including verbal and nonverbal, immediate and delayed, attention and concentration, sequential recall, free recall, associative recall, and multiple-trial learning memory. All index and nearly all subtest differences remained significant even after comparing a subset of the autism group (n = 36) and controls that were matched for verbal IQ (p > .05). However, retention of previously remembered information after a delay was similar in autism and controls. CONCLUSIONS These findings indicate that performance on measures of episodic memory is broadly reduced in autism, and support the conclusion that information encoding and organization, possibly due to inefficient cognitive processing strategies, rather than storage and retrieval, are the primary factors that limit memory performance in autism.
Pharmacoepidemiology of psychotropic drugs: examples of current research challenges on major public health issues

Summary Background – As a large number of persons are exposed to prescribed psychotropic drugs, their utilisation and impact should be further explored at the population level. Aims – To illustrate the interest of pharmacoepidemiological studies of psychotropic drugs by selected examples of major public health issues. Method – Selective review of the literature. Results – Many questions remain unsolved regarding the behavioural teratogenicity of prenatal exposure to psychotropic drugs, the impact of their increasing use in children, the long-term cognitive consequences of exposure to benzodiazepines, and the risks associated with extension of indications of antipsychotic drugs. Conclusion – Pharmacoepidemiological studies need to be further developed owing to the large number of public health questions raised by the extensive and expanding use of psychotropic drugs.
Audio file steganalysis through artificial neural networks

In this study, we have developed a new steganalysis method that combines both Chi-square and PNN techniques. We have tested our steganalysis method on digital audio files. The stego files under test have been assumed to contain a secret data file embedded by a known steganography method, which is LSB (Least Significant Bit) steganography in our test environment. The method we have developed first analyzes the LSB bits in cover audio files then obtained intermediate data are applied to PNN to achieve more realistic results. While most steganalysis methods focuses on only detection of secret data, our method can also determine the rate of secret data.
Pengaruh Keputusan Investasi, Pendanaan dan Dividen terhadap Nilai Perusahaan dengan Risiko sebagai Variabel Mediasi

The aim of this research is to know the influence of investment desicion, funding and dividend to the firm value with the risk as a mediation variable. Population that is used in this research is a company manufacturing sector which is listed on Indonesia Stock Exchange in the period from 2011 until 2013. Number of sample that used in this research is 60 samples with the method purposive sampling. Firm value variable is proxied by Price Book Value Ratio (PBR), Investment decision is proxied by Price Earning Ratio (PER), financing decision subtitued by Debt to Equity Ratio (DER), dividend policy is proxied by Dividend Pay Out Ratio (DPR) and business risk subtitued by Degree of Operating Leverage (DOL). Data Analysis using multiple regression analysis and line analysis by using a SPSS 16 program. The research concluded that only the investment decisions and the funding decision which has an effect on the firm value.
The yeast A kinases differentially regulate iron uptake and respiratory function.

Yeast has three A kinase catalytic subunits, which have greater than 75% identity and are encoded by the TPK genes (TPK1, TPK2, and TPK3) [Toda, T. , Cameron, S. , Sass, P., Zoller, M. & Wigler, M. (1987) Cell 50, 277-287]. Although they are redundant for viability, the three A kinases are not redundant for pseudohyphal growth [Robertson, L. S. & Fink, G. R. (1998) Proc. Natl. Acad. Sci. USA 95, 13783-13787; Pan, X. & Heitman, J. (1999) Mol. Cell. Biol. 19, 4874-4887]; Tpk2, but not Tpk1 or Tpk3, is required for pseudohyphal growth. Genome-wide transcriptional profiling has revealed unique signatures for each of the three A kinases leading to the identification of additional functional diversity among these proteins. Tpk2 negatively regulates genes involved in iron uptake and positively regulates genes involved in trehalose degradation and water homeostasis. Tpk1 is required for the derepression of branched chain amino acid biosynthesis genes that seem to have a second role in the maintenance of iron levels and DNA stability within mitochondria. The fact that TPK2 mutants grow better than wild types on nonfermentable carbon sources and on media deficient in iron supports the unique role of Tpk2 in respiratory growth and carbon source use.
Childhood Hygiene Is Associated With the Risk for Inflammatory Bowel Disease: A Population-Based Study

OBJECTIVES:The “hygiene hypothesis” postulates that individuals raised in a sanitary environment are more likely to develop inflammatory bowel disease (IBD). Several studies previously demonstrated contradictory results in this regard. We performed for the first time a population-based study on the association of surrogate markers of childhood hygiene with the risk for IBD.METHODS:A cross-sectional population-based study was undertaken. Information on number of siblings, birth order, and living in an urban versus rural environment was obtained for 399,251 Jewish adolescents at the age of 17 yr from 1998 to 2004. The study population included only subjects born in Israel. In order to control for genetic confounding, subjects were also divided according to their ethnic group as being Ashkenazi, Sephardic, or Israeli in origin.RESULTS:In total, 768 cases of inflammatory bowel disease (IBD) were diagnosed (0.19%), with 53.8% of the cases being of Ashkenazi origin. On multivariate analysis, variables significantly associated with IBD were male gender (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.24–1.67), Ashkenazi origin (OR 1.91, 95% CI 1.63–2.22), living in an urban environment (OR 1.38, 95% CI 1.02–1.78), small number of siblings in the family (for 1 sibling vs 5 or more, OR 2.63, 95% CI 1.49–4.62), and higher birth order (for birth order of 5 or higher vs 1, OR 2.35, 95% CI 1.47–3.77), showing for both variables an almost strictly highly significant monotonic association (P value for trend <0.001). CONCLUSIONS:Surrogate markers of childhood hygiene are associated with the risk for IBD, thus reinforcing the “hygiene hypothesis. ”
The effects of chemotherapy with bleomycin, etoposide, and cis‐platinum on telomeres in rat male germ cells

Co‐administration of bleomycin, etoposide, and cis‐platinum (BEP) has increased the 5‐year survival rate of testis cancer patients to over 90%; however, this treatment induces chemotoxic effects on male germ cells. Treatment of male rats with BEP, using a similar schedule to that used in man, affects reproductive organ weights and sperm count, motility, and DNA integrity, as well as pup survival rates. Telomeres, specialized structures at the termini of chromosomes, play an important role in the maintenance of genetic stability. In previous studies, we demonstrated, using a spermatogonial cell line, that cis‐platinum and bleomycin damage telomeres and that cis‐platinum also inhibits telomerase activity. Our objective here was to test the hypothesis that in vivo exposure to the BEP regimen used to treat testis cancer targets telomeres in the male germ line. Adult male Brown Norway rats received chronic treatment with a BEP regimen. DNA double strand breaks were increased significantly in zygotene germ cells, as assessed by γ‐H2AX immunofluorescence. Interestingly, treatment with this BEP regimen increased γ‐H2AX foci in the telomere region of zygotene spermatocytes, but not in other germ cell types, such as pachytene cells, round spermatids, or elongating spermatids. Mean telomere lengths were reduced in zygotene, pachytene, round spermatid, elongating spermatid and cauda epididymal spermatozoa compared with the saline control group. Thus, telomere lengths did not recover during germ cell development. These studies demonstrate that BEP treatment is associated with an effect on telomeres.
Globalisation and Conflict: Evidence from Sub-Saharan Africa

Stephen Pinker (2011) advances that various forms of violence such as homicide, rape, torture and conflict have decreased over time because of the following historical shifts in society: pacification process, civilising process, humanitarian and rights revolutions, and extended periods of peace. We regard these shifts as modernising processes encompassed in globalisation and investigate the effects of globalisation on conflict, one of the forms of violence Pinker discusses. We use panel data from 46 sub-Saharan African countries dated 1970 to 2013 and find that increased globalisation significantly reduces severity of conflict through increased opportunity costs. Furthermore, we disaggregate globalisation into its three key components (social, political and economic openness) and find that social globalisation drives the results, an indication of the significance of increased flows of people and information in fostering tolerance and empathy. We also disaggregate conflict into intrastate and interstate and find that the severity of intrastate conflict is significantly reduced by the globalisation processes compared to interstate conflict.
Mutations, duplication, and deletion of recombined switch regions suggest a role for DNA replication in the immunoglobulin heavy-chain switch

The heavy-chain switch from immunoglobulin M (IgM) expression to IgA expression is mediated by a recombination event between segments of DNA called switch regions. The switch regions lie two to six kilobases upstream of the mu and alpha constant region coding segments. Switch recombination to IgA expression results in a recombinant mu-alpha switch region upstream of the expressed alpha constant region gene. We have characterized the products of switch recombination by a lymphoma cell line, I.29. Two sets of molecular clones represent the expected products of simple mu to alpha switches. Five members of a third set of molecular clones share the same recombination site in both the mu and the alpha switch regions, implying that the five molecular clones were derived from a single switch recombination event. Surprisingly, the five clones fall into two sets of sequences, which differ from each other by several point mutations and small deletions. Duplication of switch region sequences are also found in these five molecular clones. An explanation for these data is that switch recombination involves DNA synthesis, which results in nucleotide substitutions, small deletions, and duplications.
Elevated expression of Rad51 is correlated with decreased survival in resectable esophageal squamous cell carcinoma

Rad51 plays a critical role in homologous recombination and correlates with many human malignancies. However, its role and clinical significance in esophageal squamous cell carcinoma (ESCC) has not been clarified. The purpose of this study was to explore the clinicopathological correlation and prognostic significance of Rad51expression in a group of ESCC patients.
Rapid Mechanotransduction in Situ at the Luminal Cell Surface of Vascular Endothelium and Its Caveolae*

The vascular endothelium is uniquely positioned between the blood and tissue compartments to receive directly the fluid forces generated by the blood flowing through the vasculature. These forces invoke specific responses within endothelial cells and serve to modulate their intrinsic structure and function. The mechanisms by which hemodynamic forces are detected and converted by endothelia into a sequence of biological and even pathological responses are presently unknown. By purifying and subfractionating the luminal endothelial cell plasma membrane from tissue, we show, for the first time, that not only does mechanotransduction occur at the endothelial cell surface directly exposed to vascular flow in vivo but also increased flowin situ induces rapid tyrosine phosphorylation of luminal endothelial cell surface proteins located primarily in the plasmalemmal invaginations called caveolae. Increased flow induces the translocation of signaling molecules primarily to caveolae, ultimately activating the Ras-Raf-mitogen-activated protein kinase pathway. This signaling appears to require intact caveolae. Filipin-induced disassembly of caveolae inhibits both proximal signaling events at the cell surface and downstream activation of the mitogen-activated protein kinase pathway. With the molecular machinery required for mediating rapid flow-induced responses as seen in endothelium, caveolae may be flow-sensing organelles converting mechanical stimuli into chemical signals transmitted into the cell.
Executive dysfunction and clinical outcome in chronic alcoholics.

BACKGROUND The purpose of this study was to investigate which of 12 neuropsychological tests predict alcoholic patients' alcohol-specific and/or alcoholic-nonspecific outcome. Our hypothesis was that the ecologically valid neuropsychological tests that measure executive function are better predictors of alcoholics' functional outcome. METHODS We administered 12 neuropsychological tests to chronic alcoholics. Included in the tests were tasks of Reaction Time, Symbol Digit Modalities, Figure Position, Digit Span, Block Design, Trail Making, and six subtests of a battery called the Behavioral Assessment of the Dysexecutive Syndrome (BADS). Previous investigators have suggested that the BADS has ecological validity. Twenty-two male alcoholics were compared with 15 nonalcoholic control subjects on these neuropsychological measures 7 weeks after detoxification. Two functional outcome indices, i.e., resumption of drinking and occupation, were evaluated 18 months after discharge. RESULTS The total profile score and the score on three of the six subtests of the BADS were lower in alcoholics than in nonalcoholic controls. Alcoholics' performance on the BADS predicted alcohol-nonspecific outcome (occupation) but not alcohol-specific (drinking) outcome. In contrast, other neuropsychological tests did not predict either of the two outcome indices. CONCLUSIONS The BADS total profile score is related to alcohol-nonspecific outcome but not to alcohol-specific outcome.
Release of fibronectin-lipoteichoic acid complexes from group A streptococci with penicillin

Fibronectin binds to Streptococcus pyogenes, and this binding is inhibited by lipoteichoic acid (LTA). Previous studies have shown that LTA can be released from S. pyogenes by treatment with penicillin. Penicillin released LTA from both S. pyogenes and Staphylococcus aureus; however, the binding of fibronectin correlated with the amount of LTA released only in the case of S. pyogenes. Contrarily, clindamycin decreased the ability of S. aureus to bind fibronectin without affecting the binding of fibronectin to S. pyogenes. Further studies indicated that LTA does not inhibit the binding of fibronectin to S. aureus. Fibronectin bound to S. pyogenes could be released from the cell surface by penicillin. Immunological analysis of the released fibronectin indicated that LTA was the only surface component which could be detected as a soluble complex with the released fibronectin. These studies suggest that LTA plays a central role in the binding of fibronectin to S. pyogenes and is not involved in the binding of fibronectin to S. aureus.
Economic Impacts of the Florida Golf Course Industry

Executive Summary Economic impacts of the Florida golf industry were estimated for year 2000 based upon a survey of golf courses, together with other published data and regional economic models. A survey questionnaire was mailed to 1,334 golf courses. Responses were received from 223 firms, representing a 17 percent response rate, and results for survey respondents were extrapolated to estimate values for the entire population. The respondent golf courses were classified as private (50%), semi-private (27%), public (14%), municipal (9%), resort (5%), and military (1%). Residential developments were part of 54 percent of Florida golf courses, with some 756,000 residential units, which had an average value of $366,000 and a total value of $158Bn. Florida golf courses had 27,718 golf holes. Total annual revenues amounted to $4.44 billion (Bn), including membership and initiation fees (38%), playing fees (27%), food and beverage services (18%), retail sales (6%), lodging (4%), and miscellaneous other activities (9%). The revenues for year 2000 were 49 percent higher than a previous estimate of $3.0Bn in 1991–92, representing an average annual growth rate of 5 percent in nominal dollar terms. Florida counties with golf course revenues in excess of $100 million (Mn) were Results were also summarized for 8 economic regions of Florida. Golf industry employment was 73,000 persons, including clubhouse personnel (68%), and golf course maintenance personnel (32%), with 71 percent as full-time and 29 percent as part-time, temporary or seasonal employees. Annual expenses amounted to $3.70Bn, including golf course maintenance (29%), food and beverage service (20%), golf operations (13%), administrative overhead (12%), clubhouse (10%), capital (9%), tennis, fitness and other recreation services (4%), and miscellaneous other expenses (4%). Charitable contributions made by golf courses amounted to $12Mn in cash and $25Mn in-kind. The book value of assets owned by golf courses was $10.8Bn, including land (58%), buildings and installations (26%), vehicles and equipment (10%) and golf course irrigation systems (6%). Area owned by golf courses was 205,000 acres, with 147,000 acres in maintained turf, and 140,000 acres irrigated. Bermudagrass was the predominant type of turfgrass used on golf courses, representing 93 percent of maintained turf area. Water used for irrigation amounted to 173 billion gallons, of which recycled water was the dominant source (49%), with lesser amounts from surface waters (29%) and wells (21%). Compared to 5 years ago, water use per acre was increased by 9 percent of firms, decreased by 42 percent, and …