Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell-cycle-regulated translation of histone mRNA in Physarum plasmodia

In Physarum polycephalum, histone mRNA begins to accumulate 3 h before the S phase. We show that histone synthesis was limited to the S phase and that the mRNA that accumulated in the G2-phase cytoplasm could be translated in vitro. Thus, recruitment of stored mature histone mRNA did not occur until the S phase began.
EVIDENCE FOR ASCORBIC ACID TRANSPORT SYSTEM IN RAT BRAIN CAPILLARIES

Although ascorbic acid (AA) crosses the choroid plexus and may enter the brain at an appreciable rate, it is not clearly established that there exist transport system(s) carrying this vitamin from blood into the brain cells across the brain capillaries. Thus the rate of its uptake by choroid plexus and cerebral capillaries were evaluated in vitro in this study. Choroid plexus and brain capillaries were isolated from two-month-old male Sprague-Dawley rats. Time course of AA incorporation in micro vessels and choroid plexus was studied up to 30 min. After stopping the incorporation with the excess of cold isotonic saline, micro vessels were filtered and sonicated. The intracellular incorporated AA radioactivity was measured by liquid scintillation counting. AA uptake by micro vessel was tested for Na+-dependence and saturability. The time course studies showed linear increase in total uptake and accumulation of AA by choroid plexus and endothelial cells up to 30 min. Treatment with oubain or replacement with sodium chloride showed that uptake is an Na+- independent process. Transport of AA to cerebrospinal fluid and brain was also shown to be readily saturated by increasing the level of cold AA. These results document that the brain capillary endothelial cells are able to transport and accumulate AA, and may have a critical role in the homeostasis and regulation of cerebral ascorbic acid concentration.
Global exponential stability and synchronization of memristive neural networks including both time-varying and continuously distributed delays

This article investigates the stability and synchronization problems for a kind of general memristive neural networks (MNNs) including both time-varying and continuously distributed delays. With the help of homeomorphism theory, delay differential-integral inequality and appropriate Lyapunov-Kravsovskii functional approach, several new sufficient criteria concerning global exponential stability and synchronization for MNNs are obtained under the sense of Filippov solution. The obtained criteria make some extensions and improvements of the existing results and are easier to be validated in the numerical simulation.
Expression of the herpes simplex virus 1 alpha transinducing factor (VP16) does not induce reactivation of latent virus or prevent the establishment of latency in mice

A feature of the cascade regulation of herpes simplex virus 1 gene expression in productive infection is that the first genes to be expressed, the alpha genes, are transactivated by a structural component of the virion designated as the alpha transinducing factor (alpha TIF). In this study, we have tested the hypothesis that latent infection of sensory neurons results from the failure of alpha TIF, a tegument protein, to be transported from the nerve endings to the nucleus of the sensory neuron. Two viruses were constructed. The first recombinant virus (R6003) contained a second copy of the alpha TIF gene placed under the control of a metallothionein promoter. The second recombinant virus (R6004) is identical to R6003 except for the presence of a stop codon inserted at amino acid 70 of the second alpha TIF gene. The metallothionein promoter inserted into the viral genome was shown to be expressed, and alpha TIF mRNA was detected by in situ hybridization of sections of trigeminal ganglia of mice infected with R6003, both untreated and those given cadmium injections. In all experiments, there were no significant differences in the recovery of latent virus from mice infected with R6003 or R6004, whether injected with cadmium or not. Cadmium administration at the time of infection and at intervals thereafter did not preclude establishment of latency. In another series of experiments, transgenic mice expressing the metallothionein-driven alpha TIF did not differ from nontransgenic siblings with respect to the incidence of latent virus in trigeminal ganglia. We conclude that the absence of alpha TIF cannot alone account for the establishment of latency.
Targeted Gene Delivery to Human Airway Epithelial Cells with Synthetic Vectors Incorporating Novel Targeting Peptides Selected by Phage Display

Human airway epithelial cell targeting peptides were identified by biopanning on 1HAEo-cells, a well characterised epithelial cell line. Bound phage were recovered after three rounds of binding, high stringency washing and elution, leading to the production of an enriched phage peptide population. DNA sequencing of 56 clones revealed 14 unique sequences. Subsequent binding analysis revealed that 13 of these peptides bound 1HAEo-cells with high affinity. Three peptides, SERSMNF, YGLPHKF and PSGAARA were represented at high frequency. Three clearly defined families of peptide were identified on the basis of sequence motifs including R/KSM, LP/QHK and PSGA/TARA. Two peptides, LPHKSMP and LQHKSMP contained two motifs. Further detailed sequence analysis by comparison of peptide sequences with the SWISSPROT protein database revealed that some of the peptides closely resembled the cell binding proteins of viral and bacterial pathogens including Herpes Simplex Virus, rotavirus, Mycoplasma pneumoniae and rhinovirus, the latter two being respiratory pathogens, as well as peptide YGLPHKF having similarity to a protein of unknown function from the respiratory pathogen Legionella pneumophila. Peptides were incorporated into gene delivery formulations with the cationic lipid Lipofectin and plasmid DNA and shown to confer a high degree of transfection efficiency and specificity in 1HAEo-cells. Improved transfection efficiency and specificity was also observed in human endothelial cells, fibroblasts and keratinocytes. Therefore, on the basis of clone frequency after biopanning, cell binding affinity, peptide sequence conservation and pathogenic similarity, we have identified 3 novel peptide families and 5 specific peptides that have the potential for gene transfer to respiratory epithelium in vivo as well as providing useful in vitro transfection reagents for primary human cell types of scientific and commercial interest.
The Last Straw!: A Tool for Participatory Education About the Social Determinants of Health

Background: In response to a scarcity of teaching tools regarding the social determinants of health (SDOH), Kate Reeve and Kate Rossiter created The Last Straw! board game, an innovative participatory education tool to facilitate and engage critical thinking about the SDOH. Objectives: The Last Straw! is designed to encourage discussion about the SDOH, promote critical thinking, and build empathy with marginalized people. Methods: The game begins as each player rolls the dice to create a character profile, including socioeconomic status (SES), race, and gender. Based on this profile, players then receive a certain number of “vitality chips. ” Moving across the board, players encounter scenarios that cause them to gain and lose chips based on their profile. The player who finishes the game with the most chips wins the game. The game can be facilitated for a variety of audiences, including both players with no prior knowledge of the SDOH and those experienced in the field. Conclusions: The game has been played with students, policymakers, and community workers, among others, and has been met with immense enthusiasm. Here, we detail the game’s reception within the community, including benefits, limitations, and next steps.
Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy.

In the brains of humans and other mammals, there are two principal groups of cholinergic nuclei aside from those forming the cranial motor nuclei. One group lies in the forebrain and includes the nucleus basalis of Meynert. The second group lies in the hindbrain and includes the nucleus tegmenti pedunculopontinus (NPP), identified by Mesulam et al. [Mesulam, M. -M. , Mufson, E. J., Wainer, B. H. & Levey, A. I. (1983) Neuroscience 10, 1185-1201] as cholinergic cell group Ch5. The basal forebrain cholinergic cell groups, which innervate widespread areas of the neocortex, undergo degeneration in Alzheimer disease and also in parkinsonism associated with dementia. We here report that the hindbrain NPP Ch5 cell group, thought to innervate many nuclei of the extrapyramidal motor system, the superior colliculus, and the substantia innominata, undergoes degeneration in idiopathic Parkinson disease and in the parkinsonian syndrome of progressive supranuclear palsy. These findings strongly suggest that degeneration in the brainstem in Parkinson disease is not confined to catecholamine-containing neurons, but that cholinergic neurons of the NPP are also vulnerable. The findings further raise the possibility that certain symptoms of Parkinson disease and progressive supranuclear palsy have their genesis in pathology of these cholinergic neurons.
Childhood abuse, neglect, and household dysfunction and the risk of illicit drug use: the adverse childhood experiences study.

OBJECTIVE Illicit drug use is identified in Healthy People 2010 as a leading health indicator because it is associated with multiple deleterious health outcomes, such as sexually transmitted diseases, human immunodeficiency virus, viral hepatitis, and numerous social problems among adolescents and adults. Improved understanding of the influence of stressful or traumatic childhood experiences on initiation and development of drug abuse is needed. METHODS We examined the relationship between illicit drug use and 10 categories of adverse childhood experiences (ACEs) and total number of ACEs (ACE score). A retrospective cohort study of 8613 adults who attended a primary care clinic in California completed a survey about childhood abuse, neglect, and household dysfunction; illicit drug use; and other health-related issues. The main outcomes measured were self-reported use of illicit drugs, including initiation during 3 age categories: <or=14 years, 15 to 18 years, or as an adult (>or=19 years); lifetime use for each of 4 birth cohorts dating back to 1900; drug use problems; drug addiction; and parenteral drug use. RESULTS Each ACE increased the likelihood for early initiation 2- to 4-fold. The ACE score had a strong graded relationship to initiation of drug use in all 3 age categories as well as to drug use problems, drug addiction, and parenteral drug use. Compared with people with 0 ACEs, people with >or=5 ACEs were 7- to 10-fold more likely to report illicit drug use problems, addiction to illicit drugs, and parenteral drug use. The attributable risk fractions as a result of ACEs for each of these illicit drug use problems were 56%, 64%, and 67%, respectively. For each of the 4 birth cohorts examined, the ACE score also had a strong graded relationship to lifetime drug use. CONCLUSIONS The ACE score had a strong graded relationship to the risk of drug initiation from early adolescence into adulthood and to problems with drug use, drug addiction, and parenteral use. The persistent graded relationship between the ACE score and initiation of drug use for 4 successive birth cohorts dating back to 1900 suggests that the effects of adverse childhood experiences transcend secular changes such as increased availability of drugs, social attitudes toward drugs, and recent massive expenditures and public information campaigns to prevent drug use. Because ACEs seem to account for one half to two third of serious problems with drug use, progress in meeting the national goals for reducing drug use will necessitate serious attention to these types of common, stressful, and disturbing childhood experiences by pediatric practice.
Mobility-Flow: Solução para Handover Transparente e com Suporte à Autenticação 802.1x em Redes OpenFlow

Autenticacao do usuario e um elemento primordial para garantir niveis adequados de seguranca no acesso aos servicos corporativos estrategicos. Contudo, este procedimento pode acarretar degradacao da qualidade percebida pelo usuario quando das execucoes de handover entre pontos de acesso, uma vez que a reautenticacao e requerida. Apesar de inumeras solucoes presentes na literatura para o gerenciamento de mobilidade, a autenticacao do usuario e negligenciada. Este artigo propoe uma solucao de gerenciamento mobilidade baseada no OpenFlow para redes Wi-Fi, considerando autenticacao 802.1x. Os resultados mostram os beneficios da solucao proposta para trafego de melhor esforco e de video.
A Single Scatter Model for X-ray CT Energy Spectrum Estimation and Polychromatic Reconstruction

To improve the quantitative accuracy of linear attenuation coefficients measured by computed tomography (CT), we used a single scatter model to estimate the Compton scatter distribution and then a polychromatic image reconstruction algorithm, namely the iterative maximum-likelihood polychromatic algorithm for CT (IMPACT), was implemented to include scatter correction (SC). To perform the IMPACT, the X-ray spectra of a tube were estimated via an expectation-maximization (EM) algorithm with SC. To test the accuracy of the estimated spectra, the projection images of cubic phantoms containing different depths of polymethylmethacrylate (PMMA) were acquired. The percentage of root mean square errors (%RMSE) of the measured transmission data and calculated transmission values were used to evaluate the accuracy of the estimated spectra. In addition, a hydroxylapatite (HA) phantom was used to study streak artifacts and evaluate the accuracy of the linear attenuation coefficients estimated using the IMPACT with SC. The %RMSE of the EM-with-SC estimated spectra were all lower than 1% and were also smaller than that without SC. The error in the quantification of the HA linear attenuation was only about 3% after SC. Our results showed that the quantitative accuracy of the linear attenuation coefficients measured with a cone beam CT was improved when the IMPACT with SC was used.
Binding of Human Phospholipase A2 Type II to Proteoglycans

Phospholipase A2 acting on low density lipoproteins in the extracellular arterial intima may form proinflammatory lipid mediators. Human nonpancreatic secretory phospholipase A2 has three regions that may associate with sulfated glycosaminoglycans. The apoB-100 molecule in low density lipoproteins also has glycosaminoglycan binding regions that could mediate its retention in the arterial intima. Here we report that human nonpancreatic phospholipase A2 isolated from a transfected cell line binds to glycosaminoglycans secreted by cultured human arterial smooth muscle cells. A gel mobility shift assay showed that the affinity of phospholipase A2 for glycosaminoglycans from a heparan sulfate/chondroitin sulfate proteoglycan was higher than for chondroitin sulfate glycosaminoglycans from a larger versican-like proteoglycan. Affinity chromatography confirmed these results. All glycosaminoglycans tested, at concentrations up to 100 μM, increased the activity of phospholipase A2 toward phosphatidylcholine liposomes. Above this concentration, heparan sulfate and heparin inhibited the enzyme. Heparin and chondroitin 6-sulfate increased phospholipase A2 activity on low density lipoproteins up to 4-fold at 100 μM, whereas heparan sulfate had no effect. The results indicate that human nonpancreatic secretory phospholipase A2 interacts with proteoglycans via their glycosaminoglycan moiety and that the enzyme activity may be modulated by the association of the enzyme and its substrate to the sulfated polysaccharides.
Returns to Skills in Europe – Same or Different? The Empirical Importance of the Systems of Regressions Approach

We estimate the Mincer equations for a set of European countries. The variability of parameters, describing the impact of years of schooling and the experience to the wages, was obtained by application of the system of Seemingly Unrelated Regression Equations (SURE). The differences between parameters were tested given two alternative stochastic assumptions. In the first model, no contemporaneous correlations between error terms in the system is imposed. This may be related to the standard country regression approach. In the second approach the unrestricted covariance matrix is considered, making error terms stochastically dependent. The contemporaneous correlations of error terms in the SURE system were empirically supported. Also, rich parameterisation of covariance matrix of contemporaneous relations reduced statistical uncertainty about differences in parameters describing return on education effect. Consequently, the country heterogeneity of return on education, which seems intuitively correct, was obtained in the system of regressions with complex stochastic structure.
Role of cytokines in rheumatoid arthritis.

Cytokines have emerged as crucial players in mediating synovial inflammation in the rheumatoid joint, where the local and systemic production of cytokines appears to account for most of the pathologic and clinical manifestations of rheumatoid arthritis. Among the cytokines, tumor necrosis factor-alpha and interleukin-1 are considered to be of great importance in the pathogenesis of the disease. Other pro-inflammatory cytokines in rheumatoid arthritis are interleukin-6, interleukin-8, leukemia inhibitory factor, granulocyte-macrophage colony-stimulating factor and transforming growth factor-beta The potent antiinflammatory cytokines interleukin-4 and interleukin-10, which are powerful inhibitors of most of these mediators, seem to be promising agents and candidates for an optimal approach to treatment.
Association of circulating regulatory T cell number with the incidence and prognosis of diffuse large B‐cell lymphoma

Regulatory T (Treg) cells are essential for maintaining immune tolerance. High Treg frequencies have been reported in peripheral blood and tissue samples of patients with solid tumors while their role in lymphomas, including diffuse large B‐cell lymphoma (DLBCL) has not been clearly established. In this study, we analyzed the circulating Treg numbers in 27 patients with newly diagnosed DLBCL and 17 healthy individuals. Tregs were detected by flow cytometry based on CD4+CD25highFoxP3+ phenotype. In addition, the expression of CD45RA, HLA‐DR, CD62L, CD39, and CTLA4 was analyzed. The number of circulating Treg cells was lower in patients with DLBCL than in healthy controls: median 23 (range, 4–107)/μL vs. 41 (19–104)/μL (P = 0.04). In particular, the number of Tregs expressing CD45RA (naïve Tregs), HLA‐DR (marker of activation), and CD62L (L‐selectin) was decreased in the DLBCL group. Lower (below median) number of circulating Tregs was associated with reduced chance of achieving complete remission (29% vs. 69%, P = 0.05) and reduced probability of even‐free survival (24% vs. 84% at 1 yr, P = 0.0004), independently on the International Prognostic Index. We conclude that low number of circulating Tregs may be associated with poor prognosis in patients with DLBCL. However, our observations require confirmation in larger patient population.
Building Customer Relationship through Game Mechanics in Social Games

This chapter examines mechanics of game design in social games that are used in building customer relationship. The developments in the game industry towards service orientation, and increased emphasis on social design, have resulted in overlap of game design and business design. This chapter examines the junction of these domains in contemporary social games, by studying how game design is used in pursuing business goals of the related business models. Several virtual worlds and social games are examined with the support of secondary data provided by experts in the field. The identified mechanics are then categorised and analysed in the context of business model literature on customer relationship building. The results provide several game mechanics that are located in the union of game design and business planning. Moreover, the results imply a new approach to game design in general by exemplifying how the traditional way of thinking about game design is no longer sufficient when the design of engaging mechanics needs to meet with business goals.
Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer

Background and objective: In clinical settings with fixed resources allocated to predictive genetic testing for high-risk cancer predisposition genes, optimal strategies for mutation screening programmes are critically important. These depend on the mutation spectrum found in the population under consideration and the frequency of mutations detected as a function of the personal and family history of cancer, which are both affected by the presence of founder mutations and demographic characteristics of the underlying population. The results of multistep genetic testing for mutations in BRCA1 or BRCA2 in a large series of families with breast cancer in the French-Canadian population of Quebec, Canada are reported. Methods: A total of 256 high-risk families were ascertained from regional familial cancer clinics throughout the province of Quebec. Initially, families were tested for a panel of specific mutations known to occur in this population. Families in which no mutation was identified were then comprehensively tested. Three algorithms to predict the presence of mutations were evaluated, including the prevalence tables provided by Myriad Genetics Laboratories, the Manchester Scoring System and a logistic regression approach based on the data from this study. Results: 8 of the 15 distinct mutations found in 62 BRCA1/BRCA2-positive families had never been previously reported in this population, whereas 82% carried 1 of the 4 mutations currently observed in ⩾2 families. In the subset of 191 families in which at least 1 affected individual was tested, 29% carried a mutation. Of these 27 BRCA1-positive and 29 BRCA2-positive families, 48 (86%) were found to harbour a mutation detected by the initial test. Among the remaining 143 inconclusive families, all 8 families found to have a mutation after complete sequencing had Manchester Scores ⩾18. The logistic regression and Manchester Scores provided equal predictive power, and both were significantly better than the Myriad Genetics Laboratories prevalence tables (p<0.001). A threshold of Manchester Score ⩾18 provided an overall sensitivity of 86% and a specificity of 82%, with a positive predictive value of 66% in this population. Conclusion: In this population, a testing strategy with an initial test using a panel of reported recurrent mutations, followed by full sequencing in families with Manchester Scores ⩾18, represents an efficient test in terms of overall cost and sensitivity.