Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction between PCNA and Diubiquitinated Mcm10 Is Essential for Cell Growth in Budding Yeast

ABSTRACT The minichromosome maintenance protein 10 (Mcm10) is an evolutionarily conserved factor that is essential for replication initiation and elongation. Mcm10 is part of the eukaryotic replication fork and interacts with a variety of proteins, including the Mcm2-7 helicase and DNA polymerase alpha/primase complexes. A motif search revealed a match to the proliferating cell nuclear antigen (PCNA)-interacting protein (PIP) box in Mcm10. Here, we demonstrate a direct interaction between Mcm10 and PCNA that is alleviated by mutations in conserved residues of the PIP box. Interestingly, only the diubiquitinated form of Mcm10 binds to PCNA. Diubiquitination of Mcm10 is cell cycle regulated; it first appears in late G1 and persists throughout S phase. During this time, diubiquitinated Mcm10 is associated with chromatin, suggesting a direct role in DNA replication. Surprisingly, a Y245A substitution in the PIP box of Mcm10 that inhibits the interaction with PCNA abolishes cell proliferation. This severe-growth phenotype, which has not been observed for analogous mutations in other PCNA-interacting proteins, is rescued by a compensatory mutation in PCNA that restores interaction with Mcm10-Y245A. Taken together, our results suggest that diubiquitinated Mcm10 interacts with PCNA to facilitate an essential step in DNA elongation.
HLA class II polymorphisms in Spanish melanoma patients: homozygosity for HLA‐DQA1 locus can be a potential melanoma risk factor

Background The association of melanoma with HLA class II loci is under extensive debate. Different investigators have found discrepant results due to, at least in part, sample size, patient series heterogeneity, choice of control population and differences in the techniques employed for the detection of HLA antigens and alleles.
Theiler's murine encephalomyelitis virus kills restrictive but not permissive cells by apoptosis

Theiler's murine encephalomyelitis viruses (TMEV), genus Cardiovirus, family Picorniviridae, are natural enteric pathogens of mice which cause central nervous system demyelination similar to that seen in multiple sclerosis. TMEV can be classified into two groups based on neurovirulence: a highly virulent group, e.g., GDVII virus, and a less virulent group, e.g., BeAn virus. Both viruses, depending on the multiplicity of infection, produced cytopathology in BSC-1 cells similar to that in BHK-21 cells. Since apoptosis has been reported as a mechanism of cell death after infection with many viruses, we examined infected BHK-21 and BSC-1 cells for morphological and biochemical changes consistent with apoptosis. Only the restrictive BSC-1 cells showed evidence of nuclear morphology and internucleosomal DNA degradation indicative of apoptosis. Interestingly, the more virulent GDVII virus was at least 50-fold more efficient in inducing apoptosis than the less virulent BeAn virus. This difference was not due to greater GDVII viral RNA replication or production of infectious virus, since the two viruses were similarly restricted in BSC-1 cells. Apoptosis in BSC-1 cells appears to be triggered by a cytoplasmic event, since inactivation of GDVII viral RNA by UV light abolished the ability of the virus to induce apoptosis. The possible role of apoptosis in the pathogenesis of TMEV infection in mice, especially virus persistence in central nervous system macrophages, is discussed.
Increasing incidence of ischemic stroke in patients with HIV infection

Background: Large-scale epidemiologic data on stroke in HIV-infected persons are scarce, especially in an era of combination antiretroviral therapies, which have prolonged patient survival, but may boost stroke risk. We assessed trends in the proportion of HIV infection among patients with stroke in the United States. Methods: Data were obtained from all states within the United States that contributed to the Nationwide Inpatient Sample. All patients admitted to hospitals between 1997 and 2006 with a primary discharge diagnosis of stroke (identified by the International Classification of Diseases, Ninth Revision procedure codes) were included. Time trends in the proportion of these patients with HIV diagnosis were computed, and independent predictors of comorbid HIV diagnosis evaluated using multivariable logistic regression. Results: Of all (ischemic and hemorrhagic) stroke hospitalizations, patients with comorbid HIV infection constituted 0.09% in 1997 vs 0.15% in 2006 (p < 0.0001). Actual numbers of overall US stroke hospitalizations lessened 7% (998,739 to 926,997), while actual numbers of stroke hospitalizations with coexisting HIV infection rose 60% (888 to 1,425). Patients with comorbid HIV infection comprised 0.08% of ischemic strokes in 1997 vs 0.18% in 2006 (p < 0.0001), but their proportion of hemorrhagic strokes did not significantly change. Factors independently associated with higher odds of comorbid HIV diagnosis were Medicaid insurance, urban hospital type, dementia, liver disease, renal disease, and cancer. Conclusion: Over the last decade in the United States, there has been a substantial and significant rise in patients hospitalized for stroke with coexisting HIV infection. This has important public health and socioeconomic consequences.
Fire Ant Venom Alkaloid, Isosolenopsin A, a Potent and Selective Inhibitor of Neuronal Nitric Oxide Synthase

Massive, multiple fire ant, Solenopsis invicta, stings are often treated aggressively, particularly in the elderly, despite limited evidence of systemic toxicity due to the venom. Over 95% of the S. invicta venom is composed of piperidine alkaloid components, whose toxicity, if any, is unknown. To assess a possible pharmacological basis for systemic toxicity, an alkaloid-rich, protein-free methanol extract of the venom from whole ants was assayed for inhibitory activity on the following nitric oxide synthase (NOS) isoforms, rat cerebellar neuronal (n NOS), bovine recombinant endothelial (e NOS), and murine recombinant immunologic (i NOS). Cytosolic NOS activity was determined by measuring the conversion of [3H]arginine to [3H]citrulline in vitro. Rat n NOS activity was inhibited significantly and in a concentration-dependent manner by the alkaloid-rich venom extract. For n NOS, enzyme activity was inhibited by approximately 50% with 0.33 ± 0.06 μgg of this venom extract, and over 95% inhibition of the three isoforms, n NOS, e NOS, and i NOS, was found with doses of 60 μg in 60-μl reaction mixture. These results indicate that the alkaloid components of S. invicta venom can produce potent inhibition of all three major NOS isoforms. Isosolenopsin A (cis-2-methyl-6-undecylpiperidine), a naturally occurring fire ant piperidine alkaloid, was synthesized and tested for inhibitory activity against the three NOS isoforms. Enzyme activities for n NOS and e NOS were over 95% inhibited with 1000 μM of isosolenopsin A, whereas the activity of i NOS was inhibited by only about 20% at the same concentration. The IC50 for each of three NOS isoforms was approximately 18 ± 3.9 μM for n NOS, 156 ± 10 μM for e NOS, and >1000 μM for i NOS, respectively. Kinetic studies showed isosolenopsin A inhibition to be noncompetitive with L-arginine (Ki = 19 ± 2 μM). The potency of isosolenopsin A as an inhibitor of n NOS compares favorably with the inhibitory potency of widely used n NOS inhibitors. Inhibition of NOS isoforms by isosolenopsin A and structurally similar compounds may have toxicological significance with respect to adverse reactions to fire ant stings.
How Normal Is ‘Normal'?: Mild Tremor in a Multiethnic Cohort of Normal Subjects

Background While many "normal" subjects exhibit mild clinically detectable tremor, the extent to which this tremor is present has received little attention. Objective To characterize the prevalence and clinical characteristics of mild, clinically detectable tremor in a multiethnic cohort of normal subjects. Methods Normal control subjects (n=36) and their relatives (n=67) were enrolled in a community-based case-control study of the familial aggregation of essential tremor. Subjects underwent a tremor interview and videotaped tremor examination. Two neurologists independently rated the severity of tremor during different postures and tasks, and a total tremor score (maximum score, 36) was calculated for each subject. Eight subjects were randomly selected to undergo quantitative computerized tremor analysis. Results In 103 normal subjects (36 control subjects and 67 relatives of control subjects) the mean total tremor score was 4.8 (range, 0-12.5). Ninety-nine (96%) of 103 subjects had tremor, as defined by a total tremor score of 0.5 or higher. For most tasks, the mean tremor score was greater in the nondominant than in the dominant arm. The total tremor score correlated highly with age ( r =0.28; P =.004). There were no sex or ethnic differences in the mean total tremor scores. On tremor analysis, the amplitude and frequency of the tremor differed from that in a group of similarly studied subjects with essential tremor. Conclusions Normal subjects almost uniformly have a clinically detectable tremor that is mild and age dependent. Characterization of this tremor helps to establish standards for normal tremor. These standards are crucial for accurate diagnostic classification in population-based studies of essential tremor.
Integration of actomyosin contractility with cell-cell adhesion during dorsal closure

In this work, we combine genetic perturbation, time-lapse imaging and quantitative image analysis to investigate how pulsatile actomyosin contractility drives cell oscillations, apical cell contraction and tissue closure during morphogenesis of the amnioserosa, the main force-generating tissue during the dorsal closure in Drosophila. We show that Myosin activity determines the oscillatory and contractile behaviour of amnioserosa cells. Reducing Myosin activity prevents cell shape oscillations and reduces cell contractility. By contrast, increasing Myosin activity increases the amplitude of cell shape oscillations and the time cells spend in the contracted phase relative to the expanded phase during an oscillatory cycle, promoting cell contractility and tissue closure. Furthermore, we show that in AS cells, Rok controls Myosin foci formation and Mbs regulates not only Myosin phosphorylation but also adhesion dynamics through control of Moesin phosphorylation, showing that Mbs coordinates actomyosin contractility with cell-cell adhesion during amnioserosa morphogenesis. Summary: In the Drosophila embryo, control of myosin phosphorylation regulates actomyosin pulsatile activity, cell shape oscillations, adhesion dynamics and tissue morphogenesis.
Visual outcomes in patients with open globe injuries compared to predicted outcomes using the Ocular Trauma Scoring system.

AIM To determine the visual outcomes in adult patients who sustained open globe injuries and to determine whether the visual prognosis following an eye injury in an African setting differs from the predicted outcomes according to the Ocular Trauma Score (OTS) study. A secondary aim was to establish the evisceration rate for these injuries and assess how this form of intervention affected outcomes in comparison to the OTS. METHODS A prospective case series of all patients admitted with open globe injuries over a two-year (July 2009 to June 2011) period. Injuries were scored using the OTS and the surgical intervention was recorded. The best corrected visual acuity at three months was regarded as visual outcome. RESULTS There were 249 open globe injuries, of which 169 patients (169 eyes) completed the 3-month follow-up. All patients underwent primary surgery, 175 (70.3%) repairs, 61 (24.5%) eviscerations and 13 (5.2%) other procedures. Globe eviscerations were mainly done on OTS Category 1 cases, but outcomes in this category were not found to be different from OTS outcomes. Outcomes were significantly worse in Category 2, but when the entire distribution was tested, the differences were not statistically significant. The overall association between OTS outcomes and the final visual outcomes in this study was found to be a strong (P<0.005). CONCLUSION Reliable information regarding the expected outcomes of eye injuries will influence management decisions and patient expectations. The OTS is a valuable tool, the use of which has been validated in many parts of the world-it may also be a valid predictor in an African setting.
Sustainability and marketing in tourism: its contexts, paradoxes, approaches, challenges and potential

ABSTRACT Tourism marketing has typically been seen as exploitative and fuelling hedonistic consumerism. Sustainability marketing can, however, use marketing skills and techniques to good purpose, by understanding market needs, designing more sustainable products and identifying more persuasive methods of communication to bring behavioural change. This article summarises the latest research on the theories, methods and results of marketing that seeks to make tourist destinations better places to live in, and better places to visit. It explores sustainability marketing's two fundamental approaches, that of market development, using market segmentation, and that of sustainable product development. It introduces a Special Issue of the Journal of Sustainable Tourism on sustainable marketing, sharing evidence on the motivations, mechanisms and barriers that businesses encounter, and on successes in changing consumer behaviour and pursuing sustainability goals. Particular attention is given to the methodologies of sustainable tourism marketing, to the subject's breadth and complexity, and to its many innovations. Further research is called for to fully understand what contextual aspects influence these pro-sustainability interventions to achieve which outcomes in other settings, in order to validate some of the exploratory studies discussed, and establish the feasibility of scaling up pilot studies for more general use.
THE INFLUENCE OF DOSAGE AND ROUTE OF INJECTION ON THE ANTIBODY RESPONSE OF HUMAN SUBJECTS TO THE SPECIFIC CARBOHYDRATE OF THE TYPE VIII PNEUMOCOCCUS.

The readiness with which immune bodies could be demonstrated in human subjects following the injection of the specific carbohydrate of the Type VIII pneumococcus (1) offered an opportunity to study, in man, the effect of dosage and of the route of injection upon antibody production with a carbohydrate antigen. Although numerous investigators have made similar studies with whole bacterial antigens in lower animals and in man, no data are available concerning the comparative antigenic activity, in man, of purified bacterial fractions given in different amounts or by different routes. The development of antibodies following injections of type-specific polysaccarides was first demonstrated by Francis and Tillett (2) in the course of their investigations on cutaneous reactions in lobar pneumonia.
Antiviral Potency of APOBEC Proteins Does Not Correlate with Cytidine Deamination

ABSTRACT The human cytidine deaminases APOBEC3G (hA3G) and APOBEC3F (hA3F) are intracellular antiretroviral factors that can hypermutate nascent reverse transcripts and inhibit the replication of human immunodeficiency virus type 1 (HIV-1). Both enzymes have two cytidine deaminase motifs, although only the C-terminal motif is catalytic. Current models of APOBEC protein function imply editing is the principal mechanism of antiviral activity. In particular, hA3G is a more potent inhibitor of HIV-1 infectivity than hA3F and also induces a greater frequency of mutations in HIV-1 cDNA. We used hA3G/hA3F chimeric proteins to investigate whether cytidine deaminase potential reflects antiviral potency. We show here that the origin of the C-terminal deaminase motif is sufficient to determine the degree of mutation induced in a bacterial assay that measures mutations in chromosomal DNA. In contrast, this was not the case in the context of HIV-1 infection where the N-terminal deaminase motif also modulated the editing capabilities of the chimeras. Surprisingly, although three of the chimeric proteins induced levels of mutation that approximated those of parental hA3F, they displayed lower levels of antiviral activity. Most importantly, real-time PCR experiments revealed that the quantity of reverse transcripts detected in target cells, rather than the mutational burden carried by such DNAs, corresponded closely with viral infectivity. In other words, the antiviral phenotype of APOBEC proteins correlates with their ability to prevent the accumulation of reverse transcripts and not with the induction of hypermutation.
Perceptions of inservice training needs and attitudes of foreign language teachers in Massachusetts

PERCEPTIONS OF IN-SERVICE TRAINING NEEDS AND ATTITUDES OF FOREIGN LANGUAGE TEACHERS IN MASSACHUSETTS SEPTEMBER 1990 KATHLEEN M. RIORDAN, A.B. , COLLEGE OF OUR LADY OF THE ELMS M.A.T. , ASSUMPTION COLLEGE Ed.D. , UNIVERSITY OF MASSACHUSETTS Directed by: Professor William C. Wolf, Jr. The general purpose of this study was to obtain information about foreign language teachers' instructional practices, evaluation procedures, and attitudes. The specific purposes were: 1. To obtain relevant demographic and attitudinal data pertaining to the in-service training needs of selected foreign language teachers. 2. To apply data obtained to in-service training program planning initiatives. 3. To study the relationships between demographic and attitudinal data obtained and in-service training program planning. The study outcomes present a demographic profile which suggests a generally healthy climate for foreign language education in the state as evidenced by teachers' professional involvement, awareness of current practices, concern about issues, and agreement with a proficiencyoriented approach to foreign language education.
Analysis of frequency domain dielectric response of pressboard insulation impregnated with different insulating liquids

This study investigates the influence of moisture, temperature and diverse oil properties on the frequency domain response of pressboard insulation samples, which are impregnated with four different insulating liquids including two commercially available natural esters, one synthetic ester and mineral oil. Measurements are performed over a wide frequency range from 0.1 mHz to 1 kHz at variable moisture contents and temperatures (35, 55 and 75°C). It has been found that dielectric response is extremely sensitive to moisture content regardless of the type of impregnated liquid. Furthermore, dielectric response behaviour of ester impregnated pressboard insulation is qualitatively resembles to that of mineral oil impregnated pressboard which contains two distinct relaxation processes including Quasi-DC (q-dc) conduction features at low frequencies, and loss peak behaviour at mid frequency range. This paper proposes that the loss peak arises due to cooperative microscopic motion in water cellulose mixed phase dipole clusters together with the microscopic level interfacial polarization occurring at the interface of oil filled cavities. It is also discussed the q-dc process in pressboard insulation due to the charge transport between water and oil cavity based charge clusters through a percolation network of water molecules and hydroxyl groups along the cellulose fiber wall. In order to provide better understanding on charge transport and polarization phenomena in oil impregnated pressboard insulation, this paper also proposes an equivalent circuit, which is mainly derived based on Dissado- Hill (DH) cluster framework theory. Furthermore, this study has used activation energy to characterize the temperature dependent dielectric response of pressboard impregnated in mineral oil, natural esters and synthetic esters.
Chromosome 5 and Gilles de la Tourette syndrome: Linkage in a large pedigree and association study of six candidates in the region

Gilles de la Tourette Syndrome (TS) is a neuropsychiatric disorder characterized by both motor and vocal tics. In our previous genome scan for TS we identified evidence for linkage to the centromeric region of chromosome 5 in a single large family of 32 individuals with 10 family members with TS or chronic multiple tics (CMT). In this paper we report further analyses of the 5p‐centromeric region in this pedigree. An additional 11 family members were identified and screened for TS. Using a set of 14 microsatellite markers we refined the linked region to a ∼28 Mb interval between the markers D5S1506 and D5S76. A set of six candidate genes located in this region were selected to be tested for genetic association with TS. These genes were GDNF, ITGA1, ISL1, FGF10, HCN1 and SLC1A3. The TDT statistic was used for the association tests in a sample of 171 independent nuclear families with 241 affected children with TS. We found no evidence for an association between TS and markers in these genes in this sample of families. This study represents the first efforts to narrow the linkage region in the extended pedigree and the first tests of candidate genes in the chromosome 5 region linked to TS. © 2008 Wiley‐Liss, Inc.
Prevalence of noncavitated and cavitated carious lesions in a group of 5-year-old Turkish children in Kadikoy, Istanbul.

PURPOSE The present study aimed to assess the prevalence of noncavitated and cavitated caries lesions in a group of five year old Turkish children. METHODS A set of caries diagnostic criteria differentiating between active and inactive caries lesions at both noncavitated and cavitated levels was used to assess the caries status of the children. The examinations were performed on 300 children between 5 and 6 years of age. RESULTS The mean number and prevalence of active shallow and deep cavitated caries lesions (2.43+/-0.22, 21.67% and 3.39+/-0.41, 16%) were found higher than active and inactive noncavitated caries lesions (1.70+/-0.16, 14.67% and 1.78+/-0.12, 15.67%). The mean dft and dfs score were determined as 1.93+/-0.17 and 2.47+/-0.29. The mostly affected surface by both noncavitated and cavitated lesions was occlusal of second molars in both arches, whereas the mean number of both type of lesions were much more higher in mandibular second molars. A significant association between the presence of noncavitated and cavitated lesions was found (chi(2)=15.56, p<0.05). CONCLUSIONS Dental caries prevalence was relatively low in the primary dentition and the cavitated caries lesions were more common than the noncavitated lesions, however the prevalence of active and inactive noncavitated lesions were found considerably high in this group of Turkish children.
Application of Heston’s Model to the Chinese Stock Market

ABSTRACT This article applies Heston’s (1993) stochastic volatility model to the Chinese stock market indices and subsequently assesses its pricing performance. A two-step estimation procedure is adopted to calibrate Heston’s model. First, we find that the option price is affected by both the moneyness and the maturity. Second, Heston’s model is more likely to overprice options, whereas the BS model tends to underestimate options. Finally, Heston’s model, by employing volatility as a random process, significantly improves the pricing accuracy compared to the BS model. Therefore, Heston’s model is tractable to analyze the Chinese stock market indices, and there is volatility risk that must not be overlooked in the Chinese stock market.