Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative polymerase chain reaction analysis of herpes simplex virus DNA in ganglia of mice infected with replication-incompetent mutants

To study the roles of viral genes in the establishment and maintenance of herpes simplex virus (HSV) latency, we have developed a polymerase chain reaction assay that is both quantitative and sensitive. Using this assay, we analyzed the levels of viral DNA in trigeminal ganglia of mice inoculated corneally with HSV mutants that are defective for virus replication at one or more sites in mice and for reactivation upon ganglionic explant. Ganglia from mice infected with thymidine kinase-negative mutants, which replicate at the site of inoculation and establish latency but do not replicate acutely in ganglia or reactivate upon explant, contained a range of levels of HSV DNA that overlapped with the range found in ganglia latently infected with wild-type virus. On average, these mutant-infected ganglia contained one copy of HSV DNA per 100 cell equivalents (ca. 10(4) molecules), which was 50-fold less than the average for wild-type virus. Ganglia from mice infected with a ribonucleotide reductase deletion mutant, which is defective for acute replication and reactivation upon ganglionic explant, also contained on average one copy of HSV DNA per 100 cell equivalents. We also detected substantial numbers of HSV DNA molecules (up to ca. 10(3] in ganglia of mice infected with an ICP4 deletion mutant and other replication-negative mutants that are severely impaired for viral DNA replication and gene expression. These results raise the possibility that such mutants can establish latency, which could have important implications for mechanisms of latency and for vaccine and antiviral drug development.
The implementation of restorative justice policy : a case study of one police force in England and Wales

The implementation and subsequent embedding of restorative justice across a police force is fraught with difficulties, including cultural barriers to reform, structural barriers including management and hierarchy, and practical barriers for those officers tasked with ‘doing’ restorative justice within the confines of traditional criminal justice processes. There is also a lack of consistent understanding across a police force in relation to what restorative justice entails, and as to the key values and principles that underpin it. This thesis analyses the implementation process of restorative justice across one police force in England and Wales. The study sought to understand the key opportunities, constraints and limitations with regards to the implementation of restorative justice policy. It further explored understandings of restorative justice across the force. The force was observed over an eighteen month period from July 2012 to December 2013; access was given to documents, crime recording systems, and other relevant data. Four focus groups were conducted with thirty one participants representing frontline officers from different commands across all four force localities. A further ten interviews were conducted, eight with managers who were members of the restorative justice steering group, one with the Chief Constable and one with the newly-elected Police and Crime Commissioner. The research found evidence of a ‘continuum of understanding’ demonstrating the subtle differences in the ways in which different ranking officers conceptualise restorative justice. The research also identifies some of the key barriers to successful implementation. These factors included a top down implementation process which neglected the role of the community, and failed to empower officers or offer them meaningful involvement in the implementation prompting resistance both from frontline workers and middle management. It also found a great deal of confusion due to mixed messages, and a lack of concrete details which left many officers unable to fully understand and utilise restorative processes. Certain factors were also identified which helped to propel the implementation process. These included strong leadership and a small but significant culture shift across the organisation. The findings of this research are relevant beyond the police force that was the subject of the research and contain important lessons in terms of the roll out of new policy initiatives.
Pharmacokinetics of ceftiofur and metabolites after single intravenous and intramuscular administration and multiple intramuscular administrations of ceftiofur sodium to dairy goats.

Twelve (12) lactating dairy goats (46-71 kg body wt at study initiation) were divided into four treatment groups and dosed with ceftiofur sodium at 1.1 mg ceftiofur free acid equivalents (CFAE)/kg or 2.2 CFAE/kg using a complete two route (intravenous, i.v.; intramuscular, i.m.), two-period crossover design, with a 2-week washout between injections. After another 2-week washout period, the goats were dosed with ceftiofur sodium i.m. for 5 consecutive days at either 1.1 or 2.2 mg CFAE/kg. The goats from the 2.2 mg/kg multiple dose group were dried off and the i.v. kinetic study repeated. After all injections, blood samples were obtained serially for determination of combined serum concentrations of ceftiofur and metabolites. After intravenous doses of 1.1 and 2.2 mg/kg, the harmonic means of the terminal phase half-lives were 171.8 and 233 min, respectively, for lactating does. The harmonic mean of the terminal phase half-life after an i.v. dose of 2.2 mg/kg in non-lactating does was 254 min. The AUC0-infinity was significantly less and the clearance significantly greater during lactation. After i.m. doses of 1.1 and 2.2 mg/kg, the harmonic mean terminal phase half-lives were 163 and 156 min, respectively. The i.m. bioavailability of ceftiofur sodium in goats was 100%, and the AUC0-infinity was dose-proportional from 1.1-2.2 mg CFAE/kg body weight. After five daily i.m. doses of ceftiofur sodium at either 1.1 or 2.2 mg CFAE, there was minimal accumulation of drug in serum as assessed by Cmax, and serum concentrations were dose-proportional after the multiple dosing regimen.
Association of Platelet and Leukocyte Counts with Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

Background and Purpose: A proinflammatory prothrombotic state may increase the risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). We studied the relationship of levels of leukocytes, platelets, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) with the development of DCI and with clinical outcome in patients with aneurysmal SAH. Methods: In 125 patients admitted within 72 h after aneurysmal SAH, we dichotomized initial blood levels at their median values and investigated the prediction of DCI with Cox proportional hazard analysis and of poor clinical outcome with logistic regression analysis. We also analyzed concentrations before and after onset of DCI with the paired-samples t test and compared changes with those in patients without DCI. Results: During the development of DCI (unrelated to treatment), patients had a larger increase in counts of platelets (difference 49 × 109/l; 95% CI: 2–98) and leukocytes (difference 2.6 × 109/l; 95% CI: 0.4–5.0) than patients without DCI during the same period. CRP increased during DCI and decreased in patients without DCI (difference 14 mg/l; 95% CI: –29 to 58). ESR increased slightly in both groups (difference 3 mm/h; 95% CI: –15 to 20). None of the determinants at baseline predicted the development of DCI. An increased risk of poor outcome predicted by a high initial leukocyte count (OR 2.5; 95% CI: 1.1–5.7) decreased after adjustment for clinical variables (OR 2.1; 95% CI: 0.8–5.5). Conclusion: Counts of platelets and leukocytes disproportionally increase during the occurrence of DCI after aneurysmal SAH. Drugs with anti-thrombotic or anti-inflammatory properties should be studied for prevention and treatment of DCI.
Human Papillomavirus in Head and Neck Cancer: Its Role in Pathogenesis and Clinical Implications

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with an annual incidence of approximately 400,000 worldwide. Although the principal risk factors for head and neck cancer remain tobacco and alcohol use, human papillomavirus (HPV) has recently been found to be etiologically associated with 20 to 25 of HNSCC, mostly in the oropharynx. HPV causes human cancers by expressing two viral oncoproteins, E6 and E7. These oncoproteins degrade and destabilize two major tumor suppressor proteins, p53 and pRb, through ubiquitination. Additional studies have shown that E6 and E7 can directly bind to multiple host proteins other than p53 and pRb (e.g., Bak and p21Cip1), further contributing to genetic instability. However, expression of E6 and E7 alone is not sufficient for cellular transformation, and the additional genetic alterations necessary for malignant progression in the setting of virus-induced genomic instability are unknown. In addition to the etiological differences, HPV-positive cancers are clinically distinct when compared with HPV-negative cancers with regard to treatment response and survival outcome, with tumor HPV-positivity being a favorable prognostic biomarker. Further understanding of carcinogenesis and clinical behavior of HPV-positive cancers will improve disease prevention, patient care, and surveillance strategies for HNSCC patients. (Clin Cancer Res 2009;15(22):675862)
Sleep breathing disorders and cognitive function in the elderly: an 8-year follow-up study. the proof-synapse cohort.

STUDY OBJECTIVES Sleep breathing disorder (SBD) may be an important factor in age-related cognitive decline. In a cohort of healthy elderly subjects, we performed an 8-y longitudinal study to assess whether changes in cognitive function occur in untreated elderly patients with SBD and without dementia and the factors implicated in these changes. DESIGN A population-based longitudinal study. SETTING Clinical research settings. PARTICIPANTS A total of 559 participants of the PROOF study aged 67 y at the study entry and free from neurological disorders were examined. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Abnormal breathing events were defined by an apnea-hypopnea index (AHI) > 15. The raw cognitive data and averaged Z-scores for the attentional, executive, and memory functions were collected at the baseline and follow-up. At baseline, AHI > 15 was found in 54% of subjects with 18% having an AHI > 30. At follow-up, the presence of abnormal breathing events was associated with a slight but significant decline in the attentional domain (P = 0.01), which was more evident in the subjects with an AHI > 30 (P = 0.004). No significant changes over time were observed in the executive and memory functions. Several indices of chronic hypoxemia, defined either as a cumulative peripheral oxygen saturation (SpO2) < 90% or a minimal SpO2, accounted for portions of the variance in the decline in attention. All observed effects were small, accounting for 4-7% of variance in multivariate models. CONCLUSION In healthy elderly subjects, various components of sleep breathing disorder at baseline were associated with small changes in selected cognitive functions specific to the attention domain after controlling for multiple comorbidities, such as sleepiness, hypertension, diabetes, anxiety, and depression. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov identifiers NCT 00759304 and NCT 00766584.
Influence of Small Vessel Disease and Microstructural Integrity on Neurocognitive Functioning in Older Individuals: The DANTE Study Leiden

BACKGROUND AND PURPOSE: Small vessel disease is a major cause of neurocognitive dysfunction in the elderly. Small vessel disease may manifest as white matter hyperintensities, lacunar infarcts, cerebral microbleeds, and atrophy, all of which are visible on conventional MR imaging or as microstructural changes determined by diffusion tensor imaging. This study investigated whether microstructural integrity is associated with neurocognitive dysfunction in older individuals, irrespective of the conventional features of small vessel disease. MATERIALS AND METHODS: The study included 195 participants (75 years of age or older) who underwent conventional 3T MR imaging with DTI to assess fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Cognitive tests were administered to assess cognitive domains, and the Geriatric Depression Scale-15 and Apathy Scale of Starkstein were used to assess symptoms of depression and apathy, respectively. The association between DTI measures and neurocognitive function was analyzed by using linear regression models. RESULTS: In gray matter, a lower fractional anisotropy and higher mean diffusivity, axial diffusivity, and radial diffusivity were associated with worse executive function, psychomotor speed, and overall cognition and, in white matter, also with memory. Findings were independent of white matter hyperintensities, lacunar infarcts, and cerebral microbleeds. However, after additional adjustment for normalized brain volume, only lower fractional anisotropy in white and gray matter and higher gray matter radial diffusivity remained associated with executive functioning. DTI measures were not associated with scores on the Geriatric Depression Scale-15 or the Apathy Scale of Starkstein. CONCLUSIONS: Microstructural integrity was associated with cognitive but not psychological dysfunction. Associations were independent of the conventional features of small vessel disease but attenuated after adjusting for brain volume.
Enhancing effect on alkalinization of the medium on the activity of erythromycin against gram-negative bacteria.

The antibacterial activity of erythromycin was markedly enhanced by alkalinization of the culture medium or urine within the clinical range (pH 6.0 to 8.2). This effect was demonstrated against recent isolates of Escherichia coli, Klebsiella pneumoniae, Enterobacter sp. , and Pseudomonas aeruginosa, as well as against Staphylococcus aureus and Streptococcus faecalis. The urine of normal volunteers was made alkaline by ingestion of sodium bicarbonate or acetazolamide (Diamox) during administration of 1.0 g of erythromycin every 8 hr; such urine was capable of inhibiting E. coli and K. pneumoniae even when diluted up to (in one instance) 128 times with broth of the same pH as the urine. Undiluted urine of the same subjects, without alkalinization, was seldom capable of inhibiting these organisms. The range of pH (6.6 to 8.6) over which the antibacterial effect was enhanced coincided with that over which there was decreasing ionization of a basic group.
Up-Regulated Expression of Extracellular Matrix Remodeling Genes in Phagocytically Challenged Trabecular Meshwork Cells

Background Cells in the trabecular meshwork (TM), the tissue responsible for draining aqueous humor out of the eye, are known to be highly phagocytic. Phagocytic function in TM cells is thought to play an important role in the normal functioning of the outflow pathway. Dysfunction of phagocytosis could lead to abnormalities of outflow resistance and increased intraocular pressure (IOP). However, the molecular mechanisms triggered by phagocytosis in TM cells are completely unknown. Methodology/Principal Findings Gene expression profile analysis of human TM cells phagocytically challenged to E. coli or pigment under physiological and oxidative stress environment were performed using Affymetrix U133 plus 2.0 array and analyzed with Genespring GX. Despite the differential biological response elicited by E. coli and pigment particles, a number of genes, including MMP1, MMP3, TNFSF11, DIO2, KYNU, and KCCN2 showed differential expression with both phagocytic ligands in all conditions. Data was confirmed by qPCR in both human and porcine TM cells. Metacore pathway analysis and the usage of recombinant adenovirus encoding the dominant negative mutant of IkB identified NF-κB as a transcription factor mediating the up-regulation of at least MMP1 and MMP3 in TM cells with phagocytosis. In-gel zymography demonstrated increased collagenolytic and caseinolytic activities in the culture media of TM cells challenge to E. coli. In addition, collagenolytic I activity was further confirmed using the self-quenched fluorescent substrate DQ-Collagen I. Conclusions/Significance Here we report for the first time the differential gene expression profile of TM cells phagocytically challenged with either E. coli or pigment. Our data indicate a potential role of phagocytosis in outflow pathway tissue homeostasis through the up-regulation and/or proteolytic activation of extracellular matrix remodeling genes.
CEO Turnover and Market Reaction in Indonesia

This research examines Chief Executive Officer (CEO) turnover and market reaction in Indonesia. The sample of this research consists of 213 CEO turnover announcements for Indonesia Stock Exchange during 2000–2010 period. T-tests were used to investigate the effect of CEO turnover announcement on abnormal stock return during the event windows periods. The results of this research show that there is positive reaction on the CEO turnover announcements. This research considers both routine and non routine CEO turnover processes. This research finds that both turnover processes have information content to investor. This research also finds positive reaction on the announcements of outsider incoming CEO, while investors do not react on the announcement of insider incoming CEO. Thus, this research provides evidence that CEO turnover announcement have information content. Keywords: CEO turnover, stock price, turnover process, the origin of incoming CEO
Probability Distribution Dynamics Explaining Agent Model Convergence to Extremism

This chapter studies continuous opinion models with extremists, and we use probability distribution models which approximate the behaviour of agents based models in order to explain their attractor patterns. The probability distribution is defined on a discrete grid in the opinion / uncertainty space. We compute the equations of probability flows between each couple of sites of the grid for different variants of the opinion influence model (bounded confidence, relative agreement and two others). The simulations show that the probability distribution models yield attractor patterns very similar to those obtained with the agent based models. Moreover, a study of the probability distribution evolution helps to better understand the process of convergence to single and double extreme attractors observed in agent based models.
Evolution of accounting in moldova: Some reflections about the importance of historical and cultural factors

Abstract Purpose The Republic of Moldova is a small country between Romania and Ukraine, which for more than 20 years since its independence, is still experiencing a painful process of economic and institutional reforms. The chapter provides, against a review of literature and national regulations, an analysis and possible perspectives of accounting harmonization processes in relation to historical and cultural preconditions. Approach/methodology Based on content analysis of national regulations and economic conditions in the Republic of Moldova, with the support of a literature review. Findings Our findings demonstrate that some features related to mentality, which have been formed as a result of long term political and cultural closeness and negation of individualistic and independent thinking values, are determining many contemporaneous changes in all spheres, including accounting. Originality/scientific value There are very few publications about accounting processes in the Republic of Moldova. It is important to analyze the case of the Republic of Moldova in the context of accounting transformation in post-Soviet countries, as almost all of them have similar historical and cultural implications. The research results may be useful for further studies about accounting evolution in post-communist states and also in the Republic of Moldova itself.
Intraindividual Cognitive Variability in Middle Age Predicts Cognitive Impairment 8–10 Years Later: Results from the Wisconsin Registry for Alzheimer’s Prevention

Abstract Objectives: Intraindividual cognitive variability (IICV) has been shown to differentiate between groups with normal cognition, mild cognitive impairment (MCI), and dementia. This study examined whether baseline IICV predicted subsequent mild to moderate cognitive impairment in a cognitively normal baseline sample. Methods: Participants with 4 waves of cognitive assessment were drawn from the Wisconsin Registry for Alzheimer’s Prevention (WRAP; n=684; 53.6(6.6) baseline age; 9.1(1.0) years follow-up; 70% female; 74.6% parental history of Alzheimer’s disease). The primary outcome was Wave 4 cognitive status (“cognitively normal” vs. “impaired”) determined by consensus conference; “impaired” included early MCI (n=109), clinical MCI (n=11), or dementia (n=1). Primary predictors included two IICV variables, each based on the standard deviation of a set of scores: “6 Factor IICV” and “4 Test IICV”. Each IICV variable was tested in a series of logistic regression models to determine whether IICV predicted cognitive status. In exploratory analyses, distribution-based cutoffs incorporating memory, executive function, and IICV patterns were used to create and test an MCI risk variable. Results: Results were similar for the IICV variables: higher IICV was associated with greater risk of subsequent impairment after covariate adjustment. After adjusting for memory and executive functioning scores contributing to IICV, IICV was not significant. The MCI risk variable also predicted risk of impairment. Conclusions: While IICV in middle-age predicts subsequent impairment, it is a weaker risk indicator than the memory and executive function scores contributing to its calculation. Exploratory analyses suggest potential to incorporate IICV patterns into risk assessment in clinical settings. (JINS, 2016, 22, 1016–1025)
A Nap But Not Rest or Activity Consolidates Language Learning

Recent evidence suggests that a period of sleep after a motor learning task is a relevant factor for memory consolidation. However, it is yet open whether this also holds true for language-related learning. Therefore, the present study compared the short- and long-term effects of a daytime nap, rest, or an activity task after vocabulary learning on learning outcome. Thirty healthy subjects were divided into three treatment groups. Each group received a pseudo-word learning task in which pictures of monsters were associated with unique pseudo-word names. At the end of the learning block a first test was administered. Then, one group went for a 90-min nap, one for a waking rest period, and one for a resting session with interfering activity at the end during which a new set of monster names was to be learned. After this block, all groups performed a first re-test of the names that they initially learned. On the morning of the following day, a second re-test was administered to all groups. The nap group showed significant improvement from test to re-test and a stable performance onto the second re-test. In contrast, the rest and the interference groups showed decline in performance from test to re-test, with persistently low performance at re-test 2. The 3 (GROUP) × 3 (TIME) ANOVA revealed a significant interaction, indicating that the type of activity (nap/rest/interfering action) after initial learning actually had an influence on the memory outcome. These data are discussed with respect to translation to clinical settings with suggestions for improvement of intervention outcome after speech-language therapy if it is followed by a nap rather than interfering activity.