Miracle-dz/UniFAR-FTUs huggingface dataset:
Transparent Distributed Cross-State Synchronization in Optimistic Parallel Discrete Event Simulation

In this report we tackle transparent deploy and seamless execution of sequentially-coded Parallel Discrete Event Simulation (PDES) models on distributed computing architectures. We present an innovative distributed synchronization protocol which allows, in conjunction with ad-hoc Operating System memory management facilities, to access the simulation state of any concurrent Logical Process (LP) running on any node of the distributed computing environment, as if it were locally hosted by a unique node - more specifically, by a unique address space. By relying on our facilities, the simulation model developer is not required to implement neither explicit message passing, nor to rely on annotations or specific programming constructs. He can simply code the accesses to the LPs' states in place (e.g. via pointers), which significantly simplifies the software development process. The burden of synchronization and correct handling of these accesses is demanded from our user-space and kernel-space runtime environment. Our proposal targets Linux on x86 64 systems and has been integrated within the ROOT-Sim open-source optimistic simulation platform, although its design principles, and most parts of the developed software, are of general relevance.
Fabrication of self-assembled folate–biotin-quaternized starch nanoparticles as co-carrier of doxorubicin and siRNA

In this paper, the starch was firstly modified by quaternary reagent to obtain cationic starch. Then self-assembled folate–biotin-quaternized starch nanoparticles were prepared by a one-pot synthesis via N,N′-dicyclohexylcarbodiimide/N-hydroxysuccinimide/4-dimethylaminopyridine-mediated esterification reaction. The physicochemical properties of the prepared folate–biotin-quaternized starch nanoparticles were characterized. The average diameter of folate–biotin-quaternized starch nanoparticles was 109 nm with polydispersity index of 0.183 and zeta potential of 28.59 mV. The folate–biotin-quaternized starch nanoparticles were used as co-carrier of siRNA and doxorubicin with satisfactory drug loading capacity (6.98%) and encapsulation efficiency (69.66 %), and siRNA could be efficiently encapsulated at 40/1 weight ratio of doxorubicin/folate–biotin-quaternized starch nanoparticles to siRNA. The folate–biotin-quaternized starch nanoparticles could effectively protect siRNA from degradation of serum RNAase for up to 48 h. The release characteristics of doxorubicin and siRNA from folate–biotin-quaternized starch nanoparticles were studied in different pH environment and the release behaviors of two drugs were all pH sensitive. The folate–biotin-quaternized starch nanoparticles as a potential co-carrier of anticancer agents and gene drugs was expected to achieve future practical application in vitro and in vivo.
CRISPR/Cas9‐mediated genome modification in the mollusc, Crepidula fornicata

The discovery and application of the CRISPR/Cas9 genome editing method has greatly enhanced the ease with which transgenic manipulation can occur. We applied this technology to the mollusc, Crepidula fornicata, and have successfully created transgenic embryos expressing mCherry fused to endogenous β‐catenin. Specific integration of the fluorescent reporter was achieved by homologous recombination with a β‐catenin‐specific donor DNA containing the mCherry coding sequence. This fluorescent gene knock‐in strategy permits in vivo observations of β‐catenin expression during embryonic development and represents the first demonstration of CRISPR/Cas9‐mediated transgenesis in the Lophotrochozoa superphylum. The CRISPR/Cas9 method is a powerful and economical tool for genome modification and presents an option for analysis of gene expression in not only major model systems, but also in those more diverse species that may not have been amenable to the classic methods of transgenesis. This approach will allow one to generate transgenic lines of snails for future studies. genesis 53:237–244, 2015. © 2014 Wiley Periodicals, Inc.
HIV-1-infected blood mononuclear cells form an integrin- and agrin-dependent viral synapse to induce efficient HIV-1 transcytosis across epithelial cell monolayer.

The heparan sulfate proteoglycan agrin and adhesion molecules are key players in the formation of neuronal and immune synapses that evolved for efficient communication at the sites of cell-cell contact. Transcytosis of infectious virus across epithelial cells upon contact between HIV-1-infected cells and the mucosal pole of the epithelial cells is one mechanism for HIV-1 entry at mucosal sites. In contrast, transcytosis of cell-free HIV-1 is not efficient. A synapse between HIV-1-infected cells and the mucosal epithelial surface that resembles neuronal and immune synapses is visualized by electron microscopy. We have termed this the "viral synapse. " Similarities of the viral synapse also extend to the functional level. HIV-1-infected cell-induced transcytosis depends on RGD-dependent integrins and efficient cell-free virus transcytosis is inducible upon RGD-dependent integrin cross-linking. Agrin appears differentially expressed at the apical epithelial surface and acts as an HIV-1 attachment receptor. Envelope glycoprotein subunit gp41 binds specifically to agrin, reinforcing the interaction of gp41 to its epithelial receptor galactosyl ceramide.
Mutation screening of muscle development genes in patients with idiopathic clubfoot

Background: Congenital idiopathic clubfoot is a very common musculoskeletal birth defect, but with no known etiology. Dietz et al. have shown possible linkage in chromosome 3 and 13 in a large, multigenerational family with congenital idiopathic clubfoot. Current evidence suggests that muscle development is impaired in patients with congenital idiopathic clubfoot, therefore we hypothesized that mutations in genes related to muscle development could be associated with this deformity. From the areas identified in the linkage study, candidate genes SPRY2, RAF1, IQSEC1, LMO7, and UCHL3 were selected based upon their presence in skeletal muscle as well as their involvement in muscle development. Methods: The exons and splice sites of the five genes were screened via sequence-based analysis in a group of 24 patients with congenital idiopathic clubfoot. All single nucleotide polymorphisms (SNPs) found were compared to public databases to determine allelic frequency and amino acid modification. Results: While many SNPs were found, none proved to be significantly associated with the phenotype of congenital idiopathic clubfoot. The SNPs found were shown to be common amongst a non-clubfoot population and to follow the allelic frequency of the general population. Conclusions: Based upon these results, SPRY2, RAF1, IQSEC1, LMO7, and UCHL3 are not likely to be the major causes of congenital idiopathic clubfoot. Given the complexity of myogenesis, many other candidate genes remain that could cause defects in the hypaxial musculature that is invariably observed in congenital idiopathic clubfoot. Clinical Relevance: This study further identifies genes which are unlikely to be the direct cause of congenital idiopathic clubfoot. It also helps to eliminate suspected genes found within the given bounds of chromosome 3 and 13.
Cyclooxygenase-2 is Overexpressed in Chronic Pancreatitis

Introduction Cyclooxygenase enzymes catalyze a critical step in the conversion of arachidonic acid to prostaglandins, which are important mediators of acute and chronic inflammation. The constitutively expressed cyclooxygenase-1 (COX-1) appears to regulate many normal physiologic functions in several cell types, whereas the inducible cyclooxygenase-2 (COX-2) enzyme mediates the inflammatory response. Aims and Methodology We investigated the expression of COX-2 in tissues of 35 patients with chronic pancreatitis, 6 patients with pancreatic cancer, and 5 control patients by immunohistochemical analysis and correlations to clinicopathologic features. Results We found an overexpression of COX-2 in the atrophic acinar cells (80% of patients), hyperplastic ductal cells (86% of patients), and islets cells (97% of patients) but not in normal pancreatic tissues. The COX-2 overexpression in the tissue of patients with chronic pancreatitis was significantly correlated with the frequency of acute attacks of pancreatitis. Tissue from patients who had more than five acute attacks of pancreatitis (n = 10) exhibited COX-2 immunoreactivity of a significantly higher score in atrophic acinar cells (p = 0.004). No correlation could be found with other examined clinical features such as duration of the disease, diabetes, alcohol consumption, smoking, or pain. Conclusion Our results support the hypothesis that COX-2 may be involved in inflammatory responses in chronic pancreatitis and in the progression of this chronic inflammatory disease.
Detecting Nature in Pictures

Com o advento da partilha em grande escala de imagens geo-referenciadas na internet, em portais como o Flickr e Panoramio, existem agora grandes fontes de dados prontas a serem processadas para a extraccao de informacao util. A utilizacao destes dados para a criacao de um mapa das areas naturais e de origem humana do nosso planeta, pode fornecer conhecimento adicional aos decisores politicos responsaveis pela conservacao do planeta.O problema de determinar o grau de naturalidade de uma imagem, pre-condicao para a criacao de tal mapa, pode ser generalizado como um problema de classificacao de paisagens. Foram executadas experiencias para melhor compreender a aplicabilidade de cada uma das tecnicas identificadas para a classificacao de paisagens quando aplicada a tarefa de distinguir entre imagens naturais e de origem humana. As suas vantagens e limitacoes, como os seus requisitos computacionais, sao detalhados.Com uma escolha cuidada das tecnicas e respectivos parâmetros foi possivel construir um classificador capaz de distinguir entre paisagens naturais e de origem humana com elevada precisao, mas tambem capaz de processar uma grande quantidade de imagens dentro de um espaco de tempo razoavel.
Chronic Depression

Defining chronic depression as persistent symptoms for 2 or more years, a prevalence of chronic depression of 12–15% is found in the literature. A four-part classification of chronic depression is proposed: Chronic Primary Major Depression; Chronic Secondary Major Depression; Characterological or Chronic Minor Depression (Dysthymic Disorder); and ‘Double Depression’. The literature indicates several factors predicting chronicity in primary major depression: more at risk are female patients, particularly those with premorbid neurotic personality traits, individuals with unipolar disorders, and those with higher familial loading for such disorders. Other factors are the adequacy and appropriateness of the treatment given, and the length of illness episode prior to treatment being received. Larger studies with well-matched controls are needed.
Endogenous adenosine modulates epileptiform activity in rat hippocampus in a receptor subtype‐dependent manner

The purine nucleoside adenosine is released during seizure activity and exerts an anticonvulsant influence through inhibition of glutamate release and hyperpolarization of neurons via adenosine A1 receptors. However, activation of adenosine A2A and A3 receptors may counteract the inhibitory effects of A1 receptors. We have therefore examined the extent to which endogenous adenosine released during seizure activity activates the different adenosine receptor subtypes and the implications for seizure activity in the rat hippocampus in vitro. Brief trains of high‐frequency stimulation in nominally Mg2+‐free artificial cerebrospinal fluid evoked epileptiform activity and resulted in a transient depression of the simultaneously recorded CA1 field excitatory postsynaptic potential. In the presence of 8‐cyclopentyl‐1,3‐dimethylxanthine (CPT), an adenosine A1 receptor antagonist, the occurrence of spontaneous seizure activity was greatly increased as was the duration and intensity of evoked seizures, whilst the postictal depression of basal synaptic transmission was greatly attenuated. Application of ZM 241385, an adenosine A2A receptor antagonist, shortened the duration of epileptiform activity, whereas administration of MRS 1191, an adenosine A3 receptor antagonist, both decreased the duration and intensity of seizures. Combined application of the A2A and A3 receptor antagonists also resulted in a reduction in seizure duration and intensity. However, no evidence was found for a role for protein kinase C in the regulation of seizure activity by endogenous adenosine. Our data confirm the dominant anticonvulsant role that endogenous and tonic adenosine play via the A1 receptor, and suggest that the additional adenosine receptor subtypes may compromise this anticonvulsant property through promotion of seizure activity.
Haematophagous feeding of newly metamorphosed European sea lampreys Petromyzon marinus on strictly freshwater species.

Approximately 6% of the freshwater living northern straight-mouth nase Pseudochondrostoma duriense in two Spanish rivers had attached post-metamorphic sea lamprey Petromyzon marinus. Minimum prey size was 16·1 cm fork length and 56·3 g mass. The condition factor of attacked P. duriense was 16% lower than that of unattacked conspecifics.
Do Tumors Grow because of the Immune Response of the Host?

The surveillance doctrine is simplistic and possesses great heuristic appeal; experiments counter to that doctrine tend, therefore, to be conveniently neglected. My purpose in this paper is to remind the reader of certain facts, some of which were developed in my laboratory, which call into question the more widely held assumptions concerning the efficacy of immunological surveillance. The surveillance hypothesis was enimciated by Thomas (1959) and amplified by Bumet (1970) and others (Good & Finstad 1969) as a result of the observation that transplanted tumors are usually immimogenic in syngeneic mice (Prehn & Main 1957) and even in the autochthonous host (lOein et al. 1960). (In this discussion a tumor is 'immunogenic' if a syngeneic animal can be immunized in such a way that growth of a subsequent tumor implant is specifically inhibited.) It now appears probable that immunogenicity may be largely a laboratory artifact it is a property apparently limited to those tumors induced in high frequency by artificial laboratory means. For example, as the dose of a chemical oncogen is decreased, the incidence of tumors declines, the latent period lengthens, and the immunogenicity declines (Prehn 1975a). At the very end of the scale, socalled 'spontaneous' tumors apparently seldom possess an appreciable capacity to induce a reaction that can interfere with their growth. The observation that 'spontaneous' tumors have little or no immunogenidty is not by itself damaging to the surveillance hypothesis. It could be argued that most tumors are indeed immunogenic, but that, in the ab-
Epidemiology of Voice Problems in Dutch Teachers

In order to assess voice complaints and absence from work due to voice problems among teachers of primary and secondary education, as well as among a control group, 2,117 questionnaires were analysed. The total group consisted of 1,878 teachers and 239 controls. Female teachers more frequently reported voice complaints and absence from work due to voice problems than their male colleagues. No unequivocal relationship between age on the one hand and voice complaints and absence from work due to voice problems on the other hand was observed. Therefore, the percent of cases was corrected for gender but not for age. More than half of the teachers reported voice problems during their career and about one fifth had a history of absence from work due to voice problems. These numbers are relatively high compared to those of the controls with as well as to those without a vocally demanding profession. More than 20% of the teachers sought medical help or had been treated for a voice problem. Remarkably, more than 12% of the teachers had experienced voice problems during their training and this group reported significantly more voice complaints and absence from work due to voice problems in their career than the colleagues without voice problems during the training. The results of the Voice Handicap Index scores followed these trends. These findings point at voice problems during education as a risk factor for getting voice problems during the career. The results of this study clearly demonstrate that teaching is a high-risk profession for the development of voice problems, which is in accordance with other studies and support the contention that voice is a worldwide problem in the teaching profession. Furthermore, this study indicates the importance of voice care not only during training for the profession but also during the career.
Socioeconomic and cultural differentials in age at marriage and the effect on fertility in Nepal

Summary Age at marriage is one of the factors that influence the fertility behaviour of women, particularly in a society like Nepal where contraceptive use is low. Socioeconomic and cultural factors, particularly religion and ethnicity, are important variables in determining age at marriage in Nepal. Fertility was negatively related with age at marriage. Marriage duration had a greater influence on fertility than age at marriage, although these were strongly correlated.
Social Health Insurance for the Poor: Targeting and Impact of Indonesia's Askeskin Program

A first step towards meeting Indonesia's ambition for universal health insurance was made in 2005 with the introduction of the health insurance for the poor (askeskin) program, a subsidized social health insurance targeted on the poor and the informal sector. this scheme covered basic healthcare in public health clinics and hospital inpatient care. in this paper we investigate targeting and impact of the askeskin program using household panel data. we find that the program is indeed targeted on the poor and those most vulnerable to catastrophic out-of-pocket health payments. the public health insurance improves access to healthcare in that it increases utilization of outpatient healthcare among the poor, while out-of-pocket spending seems to have increased for askeskin insured in urban areas. keywords: social health insurance, healthcare utilization, out-of-pocket health payments, targeting, impact evaluation, Indonesia jel classification: g22, h55, i18
Unexpected sensitivity to radiation of fibroblasts from unaffected parents of children with hereditary retinoblastoma

The response to ionizing radiation was examined in diploid skin fibroblasts derived from 5 patients with hereditary type retinoblastoma as well as their parents. Unexpected sensitivity to cell killing, as measured by clonogenic survival, as well as enhanced radiation‐induced G1 arrest were observed in at least 1 parental fibroblast strain in all 5 families. In all cases, parental strains were equally or more radiosensitive than the probands. The mutation of the retinoblastoma gene (RB) determined in 4 of 5 probands was either absent from the parental cells, as expected from the negative family histories, or identical, in 1 father who was a known carrier. In the fifth family, the family history was negative for retinoblastoma. We hypothesize that the increased parental cell sensitivity to radiation suggests the presence of an as yet unrecognized genetic event occurring in 1 or both parents of children with retinoblastoma. Whether it increases mutability of the RB locus or other loci or interacts with RB is conjectural. © 2002 Wiley‐Liss, Inc.
Tumor thickness as a prognostic factor in extramammary Paget's disease

Extramammary Paget's disease (EMPD) is a rare tumor and a widely accepted classification system specific for the disease has not been established. To elucidate prognostic factors of EMPD, we conducted a retrospective review of 145 patients with 155 EMPD lesions and investigated clinicopathological factors using univariate and multivariate analyses. We also explored tumor thickness and metastatic lymph nodes using detection analysis to determine cut‐off points for survival. All patients were Japanese (88 men and 57 women), with EMPD in the genital (82.8%), perianal (3.4%) and axillary regions (1.4%). In the remaining cases (12.4%), there were lesions at two or more regions. Univariate analysis revealed the following prognostic factors: perianal location, presence of nodules, invasion depth, tumor thickness, number of metastatic nodes and serum carcinoembryonic antigen level. Both tumor thickness and perianal location retained statistical significance in multivariate analysis (hazard ratio, 1.39; 95% confidence interval, 1.12–1.72; P = 0.0024; hazard ratio, 50.72; 95% confidence interval, 4.20–612.63; P = 0.0020; respectively). The signal detection analysis indicated tumor thickness of more than 3 mm and three or more metastatic lymph nodes as cut‐off points for survival. In conclusion, tumor thickness and the number of metastatic lymph nodes closely correlated with patient outcome and these factors could be suitable for the tumor and node classification.
Trbp Is Required for Differentiation of Myoblasts and Normal Regeneration of Skeletal Muscle

Global inactivation of Trbp, a regulator of miRNA pathways, resulted in developmental defects and postnatal lethality in mice. Recently, we showed that cardiac-specific deletion of Trbp caused heart failure. However, its functional role(s) in skeletal muscle has not been characterized. Using a conditional knockout model, we generated mice lacking Trbp in the skeletal muscle. Unexpectedly, skeletal muscle specific Trbp mutant mice appear to be phenotypically normal under normal physiological conditions. However, these mice exhibited impaired muscle regeneration and increased fibrosis in response to cardiotoxin-induced muscle injury, suggesting that Trbp is required for muscle repair. Using cultured myoblast cells we further showed that inhibition of Trbp repressed myoblast differentiation in vitro. The impaired myogenesis is associated with reduced expression of muscle-specific miRNAs, miR-1a and miR-133a. Together, our study demonstrated that Trbp participates in the regulation of muscle differentiation and regeneration.
Plasma lipid interrelationships in experimental nephrosis.

The injection 6f rmbbit anti.rat kidneyli serum induces a nephrctt ete in rats wich, 1l resemibles thiat 9ceurong atinsu jet, With the nephrotic syndrome (I). Farlier studies1from this laboratory (24) idivatedl that the incrse of plasma lipids which. ocurs in the ndphrotic rat's plasma is rrimarily die to anintravascular "trapping" phenomenon whereby the animal is unable to clear lipid from the plasma with his customary efficiency. It also was found (8, 9) that the profound deficiency of albumin characteristic of the nephrotic rat's plasma appears to be causally responsible for this retention of excess lipid in his plasma. A contributing factor may be the renal loss of heparin or its plasma equivalent, lipoprotein lipase (10). However, the sequential mechanism whereby the deficiency of albumin, and possibly also of lipoprotein lipase in nephrotic plasma, initiates and maintains the increased plasma content of all lipid fractions, remains to be elucidated. This problem has been investigated in the present studies.
Mucosal Melanomas: A Review

Summary: Mucosal melanomas, far fewer in number than melanomas of the skin, manifest a far more aggressive and more rapid life‐consuming biologic course. This behavior attends melanomas at any mucosal site, upper aerodigestive tracts, anorectum, and male and female genital tracts. Prognostic factors for both groups of melanoma are similar, but most mucosal melanomas have reached the dangerous limits, e.g., depth of invasion or thickness of melanoma at the time of diagnosis. In general, the mucosal melanomas are also more refractory to therapeutic modalities. In part, this may be due to anatomic restrictions of site and the large size of tumor when first discovered. This review presents a contemporary assessment of melanomas at all of the major mucosal sites.