Miracle-dz/UniFAR-FTUs huggingface dataset:
How dihydrofolate reductase facilitates protonation of dihydrofolate.

Dihydrofolate Reductase (DHFR) catalyzes the reduction of dihydrofolate (H2F) to tetrahydrofolate. On the basis of 10-12.5 ns molecular dynamics simulations of two conformations (closed and occluded) of the ternary DHFR/NADPH/H2F complex from Escherichia coli and a free energy perturbation approach, we have calculated the pKa value for the N5 atom in H2F. Our results suggest that the N5 atom in H2F is responsible for the pH dependency of the catalyzed reaction, meaning that DHFR facilitates protonation of H2F by approximately 4 pKa units. The mechanism behind this increase is due to favorable electrostatic interactions between the Asp27 residue and a proton at the N5 atom. The electrostatic interactions are enhanced by a hydrophobic active site, which to a large extent is made hydrophobic by the M20 loop in DHFR. Moreover, we find that the conformation imposed on H2F by DHFR to some extent also favors protonation of the N5 atom. Our results add support to previous findings and suggestions by Callender and co-workers [e.g., Deng, J.; Callender, R. J. Am. Chem. Soc. 1998, 120, 7730-7737] and explain why mutation of Asp27 may lead to severely reduced activity at neutral pH.
PCR of peripheral blood for diagnosis of meningococcal disease

Meningococcal disease is normally suspected on clinical grounds and is confirmed by isolation of Neisseria meningitidis bacteria from blood or cerebrospinal fluid or, more recently, by serology or PCR of cerebrospinal fluid. Achieving confirmation of a clinical diagnosis of meningococcal disease has become more difficult in the last few years. The pre-hospitalization administration of parenteral benzylpenicillin normally renders blood cultures sterile, and lumbar puncture is undertaken less frequently, especially in young children. We evaluated PCR for the detection of meningococcal DNA in 80 blood samples taken from patients with known or suspected meningococcal disease or from patients with other diagnoses (negative controls). Both the sensitivity and the specificity of the test were 100% for patients with confirmed cases of meningococcal disease when the blood buffy coat was used (83 to 100% sensitivity and 87 to 100% specificity with 95% confidence limits). Positive PCR results could be obtained from both blood buffy coat and serum samples. Sensitivity was unaffected by prior antibiotic treatment. PCR is a rapid, sensitive test that may be used to confirm a diagnosis of meningococcal disease by using peripheral blood samples. Introduction of this test into clinical laboratories may in some cases obviate the need for lumbar puncture to be performed on patients with suspected meningococcal disease. Our results demonstrate that a substantial number of cases of meningococcal disease are not confirmed by conventional techniques and remain undiagnosed. If the PCR test described here was widely applied, the number of cases of meningococcal disease ascertained might rise by as much as 60% greater than that recognized at present. It is likely that we are in a prevaccination era for meningococcal disease. Better case ascertainment is urgently required to assess the need for vaccines, to determine their costs and benefits, and to monitor their efficacies.
Reflections on three neophyte sport and exercise psychologists' developing philosophies for practice.

In response to the recent literature regarding the development of applied sport psychologists’ service philosophies (Lindsay, Breckon, Thomas, & Maynard, 2007), three neophyte psychologists take an autoethnographical approach to detailing how they developed their current philosophies. Using vignettes and personal accounts of their experiences they describe how reflection on their beliefs and values about people, behavior, sport, and change has underpinned their development as practitioners. The three authors detail how their delivery has developed from an approach that initially relied heavily on one framework into a more client-led approach that is more congruent with their beliefs and how this has in turn enhanced their effectiveness as practitioners. The implications of this reflective process for other neophytes is explored in relation to the experiences of the three authors.
Sexual function status in women with obstructive sleep apnea syndrome.

INTRODUCTION Several co-morbid diseases have been shown to affect sexual functions in both genders. In the literature, sexual function status in men with obstructive sleep apnea syndrome (OSAS) has been studied; however, sexual functions in women with OSAS have not yet been studied. AIMS In this prospective study, we aimed to determine sexual function status in women with OSAS and its relationship with the disease parameters of OSAS. METHODS Women, who were diagnosed with OSAS with polysomnography performed in the sleep center of our university hospital, formed the study population. Women with any genital deformity, postmenopausal women, and women without a regular partner were excluded from the study. General demographic properties, medical histories, polysomnography parameters, and frequency of intercourse per month were noted for each patient. Patients completed the Sexual Function Questionnaire Version 2 (SFQ-V2) and Epworth Sleepiness Scale. The patients were grouped as mild, moderate, and severe OSAS according to the level of respiratory disturbance index (RDI). MAIN OUTCOME MEASURES Scores of sexual function domains were determined from SFQ, and their relationships with parameters of polysomnography and demographics were studied. RESULTS Twenty-five patients were included in the study. Mean age was 48.1 +/- 2.7 years. All were married with a mean marriage duration of 25.6 +/- 3.3 years. Mean frequency of intercourse per month was 3.3 +/- 1.8. All domains of sexual functions except pain and enjoyment significantly decreased with increasing severity of OSAS. When we controlled for factors of age and co-morbid diseases, correlation analyses showed significant negative correlation between levels of RDI and all domains of sexual functions except pain and enjoyment (P < 0.05). CONCLUSIONS Obstructive sleep apnea syndrome negatively impacts sexual function in women independent of age and associated co-morbid diseases.
Case-control study of sexually transmitted diseases as cofactors for HIV-1 transmission

The aim of the study was to investigate the association between infection with HIV-1 infection and a history of other sexually transmitted diseases (STD). We were able to match 1295 HIV-1 infected patients who attended St Mary's Hospital between 1985 and 1991 with 1273 seronegative controls on gender, sexual orientation, injecting drug use and age at time of test. The cases were 3 times more likely to have a history of ever having had another STD than the controls: multivariate conditional logistic regression showed that, after controlling for sexual behaviour, for known sexual contact with an HIV infected individual or AIDS patient or with a resident from a high HIV prevalence area, area of residence and for year of test, a history of gonorrhoea, syphilis, hepatitis B, genital herpes or genital warts were all significantly associated with HIV-1 seropositive status. These findings reinforce the need for HIV containment strategies to be promoted in conjunction with containment programmes for other STDs.
A Cluster Randomised Trial of Effectiveness of Educational Intervention in Primary Health Care on Early Childhood Caries

Early childhood caries (ECC) remains a serious problem in several developing and developed countries. This cluster randomised trial evaluated the impact of a 6-month educational intervention on ECC. The trial targeted 12- to 15-month-old children (n = 242) and their mothers in Tehran, Iran, visiting 18 public health centres, randomly selected and assigned to two intervention groups and one control group. At baseline, each mother was interviewed and each child underwent a dental examination of all teeth for the number of decayed teeth (dt) and of upper central incisors for the number of teeth with enamel caries (de). All mothers in the two intervention groups (A and B) received oral health instructions from the vaccination staff. In addition, group A received extra reminders. The outcome was defined as increments in the number of teeth with dt or de, as percentages of children developing new dt or de, and as the number needed to treat (NNT). No new de appeared in group A, the mean de increment in group B was 0.2 (SD = 0.6), and in the controls, it was 0.4 (SD = 0.7) (p < 0.05). The percentages of children developing new de were 0, 14, and 26%, respectively. No differences in dt increments were found. Regarding de, NNT for group A was 4 and for B 9; the figures for dt were 13 and 17, respectively. In conclusion, oral health education given to mothers by general health staff is a valuable tool to prevent caries in infants and toddlers.
Does surgery for deep infiltrating bowel endometriosis improve fertility ? A review Running Head : Bowel endometriosis and fertility

Introduction: Reduced fertility is a major concern in women with endometriosis. The influence of surgery of deep infiltrating endometriosis (DIE) affecting the bowel wall on fertility is controversial and the literature on this field is heterogenous. In this review we addressed if surgery for bowel DIE improves spontaneous pregnancy rate and results of in vitro fertilization (IVF), and the potential risk A cc ep te d A rt ic le This article is protected by copyright. All rights reserved. of such surgery. Material and methods: We conducted a literature search including the terms “deep”, “deep infiltrating”, “bowel”, rectovaginal”, “endometriosis”, “fertility”, “infertility” and “IVF” in Pubmed. Results: No randomized controlled studies were found. Other publications of relevance included four retrospective and three prospective observational studies. Moreover, one retrospective study compared results of IVF treatment with or without previous surgery for bowel DIE. All studies included reported detailed data on surgical complications. The poor data quality precluded firm conclusions. The results indicate, however, the possibility that surgery for bowel DIE may improve the spontaneous pregnancy rate, and positive effects on IVF outcome cannot be excluded. Such surgery will be associated with risk of major complications. Conclusion: The lack of proper data preclude conclusions on the potential role for bowel DIE surgery to improve the spontaneous pregnancy rate and results of IVF treatment. Positive effects cannot be excluded, but the definite risk of major complications must be taken into account
The Bacillus subtilis Late Competence Operon comE Is Transcriptionally Regulated by yutB and under Post-Transcription Initiation Control by comN (yrzD)

ABSTRACT The Bacillus subtilis genome has been sequenced, and disruptants with disruptions in genes that were not characterized previously were systematically generated. We screened these gene disruptants for decreased transformation frequency and identified two genes, yrzD and yutB, whose disruption resulted in severely reduced transformation frequency and modestly reduced transformation frequency, respectively. In the regulation of competence development, various signals affect the expression of comK, which encodes a master regulator of genetic competence that drives late competence gene transcription. Epistatic analyses of both the yrzD and yutB genes revealed no significant differences in the expression of comK. Further analysis of the expression of late competence genes in the yrzD disruptant revealed that yrzD is specifically required for regulation of the comE operon, which is one of the late competence operons, and thus was renamed comN. An analysis of various comE-lacZ fusions revealed that the target cis element for comN action is in the large (approximately 1-kb) 5′ untranslated region of comE, while the activity of the comE promoter was not affected by disruption of comN. These results suggested that there is post-transcription initiation control of comE by comN. A sequential deletion analysis of this region revealed the 35-bp region required for comN action. The yutB gene encodes a putative lipoic acid synthetase and yet is specifically required for transcription of comE, based on the results of lacZ fusion analyses. Therefore, yutB and comN regulate comE at the transcription and post-transcription initiation levels, respectively. These results demonstrate that a comE-specific regulatory mechanism is involved in development of genetic competence.
Analgesic Effect of Sustained‐Release Flurbiprofen Administered at the Site of Tissue Injury in the Oral Surgery Model

Nonsteroidal anti‐inflammatory drugs produce their analgesic and adverse effects through interaction with cyclooxygenase in a variety of tissues. The authors evaluated the therapeutic potential of administering a sustained‐release formulation of flurbiprofen into a surgical wound following oral surgery to produce analgesia at the site of injury while minimizing exposure to potential targets for toxicity. Subjects (N = 98) received 1 of 8 treatments: flurbiprofen in a microparticle formulation in doses of 3.125 mg, 6.25 mg, 12.5 mg, 25 mg, or 50 mg; PO flurbiprofen 25 mg or 50 mg; or placebo. The flurbiprofen microparticle formulation or matching placebo was placed into the extraction sites at the end of surgery (removal of 2 lower impacted third molars). The sum of the pain visual analog scale over the 6‐hour observation period demonstrated significantly less pain (P < .05) for flurbiprofen microparticle in comparison with placebo. Fewer subjects remedicated in the flurbiprofen microparticle drug groups, primarily for the 12.5‐mg and higher doses. The incidence of adverse effects and local complications did not differ across groups. These data suggest that direct administration of flurbiprofen in a microparticle formulation at a site of tissue injury delays the onset and lowers the intensity of postoperative pain at lower doses than usually administered orally.
Recent Developments within BulTreeBank

The paper discusses recent developments in BulTreeBank (BTB). First of all, these developments include the preparatory steps for transferring richer linguistic knowledge from the original BTB into BTB-UD in order to for the enhanced dependencies to be added in the next release in May 2018. The new line of research also handles the extension of the BTB valency lexicon with subatom-based embeddings for English. The aim is to check automatically how good they are for detecting the core participants in an event. Since there are not enough resources for Bulgarian, we rely on transferring the embeddings trained on English data but enhanced with mappings to the Bulgarian WordNet and evaluated over BTB as gold standard.
GEOGRAPHIC DISTRIBUTION OF THE MUSCLE-DWELLING NEMATODE PARELAPHOSTRONGYLUS ODOCOILEI IN NORTH AMERICA, USING MOLECULAR IDENTIFICATION OF FIRST-STAGE LARVAE

Molecular identification of dorsal-spined larvae (DSL) from fecal samples indicates that the protostrongylid parasite Parelaphostrongylus odocoilei occupies a broader geographic range in western North America than has been previously reported. We analyzed 2,124 fecal samples at 29 locations from thinhorn sheep (Ovis dalli dalli and O. d. stonei), bighorn sheep (Ovis canadensis canadensis and O. c. californiana), mountain goats (Oreamnos americanus), woodland caribou (Rangifer tarandus caribou), mule deer (Odocoileus hemionus hemionus), and black-tailed deer (O. h. columbianus). The DSL were recovered from populations of thinhorn sheep south, but not north, of the Arctic Circle, and they were not recovered from any of the bighorn sheep populations that we examined. In total, DSL were recovered from 20 locations in the United States and Canada (Alaska, Yukon Territory, Northwest Territories, British Columbia, Alberta, and California). The DSL were identified as P. odocoilei by comparing sequences of the second internal transcribed spacer (ITS2) region of ribosomal RNA among 9 protostrongylid species validated by adult comparative morphology. The ITS2 sequences were markedly different between Parelaphostrongylus and other protostrongylid genera. Smaller fixed differences served as diagnostic markers for the 3 species of Parelaphostrongylus. The ITS2 sequences (n = 60) of P. odocoilei were strongly conserved across its broad geographic range from California to Alaska. Polymorphism at 5 nucleotide positions was consistent with multiple copies of the ITS2 within individual specimens of P. odocoilei. This work combines extensive fecal surveys, comparative morphology, and molecular diagnostic techniques to describe comprehensively the host associations and geographic distribution of a parasitic helminth.
Olive tree (Olea europaea L. cv. "Chemlali") under salt stress: Water relations and ions content

An experiment was conducted to evaluate the effects of salt stress on water relations and ions content of the Chemlali olive cultivar (Olea europaea L.) grown under field conditions in Sfax. Tunisia. Twelve-year-old olive trees were subjected to two drip irrigated treatments. The first is fresh water (EC of 1.2 dS m-1, control plants, CP) and the second is saline water (EC 7 dS m-1, stressed plants, SP). Leaf water relations were decreased due to salt stress. At predawn, it is of -1.4 MPa in SP and only -0.6 MPa in CP. The concentrations of Na+ and CI- ions were higher in tissues of SP. However, both Na+ and Cl- in salt stressed roots were higher than in salt stressed leaves. Salinity in root zone led to a significant decrease in K+ concentration in both leaf and root tissues of stressed plants. The Chemlali olive tree tends to cope with salt stress conditions by decreasing enormously its leaf water potential; and excluding the major part of salt ions at the root level. These mechanisms are developed in order to activate water uptake and to avoid salt ions accumulation in actively growing tissues.
Disposal of Disk and Tape Data by Secure Sanitization

User data is often unprotected on disk and tape drives or not erased when no longer needed, creating data security vulnerabilities that many computer users are unaware of. Federal and state laws require data sanitization, which comprises a variety of data eradication methods. Secure sanitization refers to methods meeting those federal and state laws. Companies that fail to meet these laws can be subject to fines of $5 million, and individuals can be imprisoned for up to 10 years. Physical destruction of storage devices offers the highest security. But executing the disk drive internal secure-erase command also offers a higher security level than external-block-overwrite software, according to federal guideline NIST 800-88. Recent disk drives with internal full disk encryption now implement an enhanced secure-erase command that takes only milliseconds to complete.
Pathology of vaginal cancers in Port Harcourt, Nigeria. A 14-year study.

BACKGROUND Primary malignancies of the vagina are rare as most are metastatic lesions. This study documents a 14-year experience in a tertiary institution in South Southern, Nigeria. DESIGN AND SETTING A retrospective study of clinical presentations including anatomic sites and histopathologic diagnosis of cancers of the vagina in the University of Port Harcourt Teaching Hospital METHODOLOGY The tissues received for histologic diagnosis were fixed in 10% formal saline, processed and embedded in paraffin wax. Microtome sections of the tissue (3 -5 microns) were taken and mounted on glass slides and stained with hematoxylin and eosin (H & E) stains. Cases in which both the slide and blocks could not be traced were excluded from the study. RESULTS A total of 2389 malignancies were diagnosed during the period under review of which 344 were gynaecological. Fifteen cases of vaginal cancers satisfied the criteria for the study, constituting 0.63% and 4.36% of the total and gynaecological malignancies respectively. Five cases (33.33%) occurred in children below the age of 20 years, while 10 cases (66.67%) were in adults. The peak incidence was in the group 0 9 and 60-69 years. Irregular vaginal bleeding was the commonest clinical presentation and the upper posterior vaginal wall was the commonest anatomic site. The most frequent histological type was the non-keratinizing squamous cell carcinoma while FIGO stage 111 (46.67%) cancer was the commonest stage at presentation. CONCLUSION Vaginal cancers are rare in this environment but they contribute to high morbidity and mortality among women of all ages as the disease is diagnosed at an advanced stage.
Simultaneous dermal matrix and autologous split‐thickness skin graft transplantation in a porcine wound model: A three‐dimensional histological analysis of revascularization

Despite the popularity of a simultaneous application of dermal matrices and split‐thickness skin grafts, scarce evidence exists about the process of revascularization involved. In this study, we aimed at analyzing the progression of revascularization by high‐resolution episcopic microscopy (HREM) in a porcine excisional wound model. Following the surgical procedure creating 5 × 5 cm2 full‐thickness defects on the back, one area was covered with an autologous split‐thickness skin graft alone (control group), the other with a collagen–elastin dermal matrix plus split‐thickness skin graft (dermal matrix group). Two skin biopsies per each group and location were performed on day 5, 10, 15, and 28 postoperatively and separately processed for H&E as well as HREM. The dermal layer was thicker in the dermal matrix group vs. control on day 5 and 28. No differences were found for revascularization by conventional histology. In HREM, the dermal matrix did not appear to decelerate the revascularization process. The presence of the dermal matrix could be distinguished until day 15. By day 28, the structure of the dermal matrix could no longer be delineated and was replaced by autologous tissue. As assessed by conventional histology and confirmed by HREM, the revascularization process was comparable in both groups, notably with regard to the vertical ingrowth of sprouting vessels. The presented technique of HREM is a valuable addition for analyzing small vessel sprouting in dermal matrices in the future.