Miracle-dz/UniFAR-FTUs huggingface dataset:
A Pivotal Role of Rho GTPase in the Regulation of Morphology and Function of Dendritic Cells1

Dendritic cell (DC) is the most potent activator of CD4+ T cells and has unique dendrites and veils. To explore the function of Rho in DC, exoenzyme C3 from Clostridium botulinum was used as a specific inhibitor of Rho. Treatment of DC with C3 (DC/C3) resulted in profound morphological changes by losing dendrites and emerging of shrunk membrane processes that were in parallel with marked reduction of polymerized actin in the marginal area. Inactivation of Rho-associated coiled coil-containing kinase (p160ROCK) by a specific ROCK inhibitor Y-27632 also led to disappearance of dendrites of DC with retaining large membrane expansions. In scanning electron microscopy, untreated DCs interacted with CD4+ T cells more efficiently than DC/C3. Conjugate formation assay showed that the number of DCs associated with CD4+ T cells was 2-fold higher in untreated DCs than that of DC/C3. Alloantigen-presenting capacity of DC/C3 was significantly suppressed in a dose-dependent manner. Because C3 treatment did not affect the surface expression of HLA, costimulatory, and adhesion molecules of DC, we examined cytokine production of DC and naive CD4+ T cells to further elucidate the inhibitory mechanism of MLR. Unexpectedly, DC/C3 increased IL-12 production after LPS stimulation. Naive CD4+ T cells cocultured with DC/C3 produced the increased percentage of IFN-γ-producing cells, whereas the percentage of IL-2-producing T cells was decreased. These results demonstrate that Rho GTPase in DC controls both characteristic shape and immunogenic capacity.
Unexpected Fees and the Prediction of Material Weaknesses in Internal Control Over Financial Reporting

We investigate whether prior year unexpected audit fees help predict new material weaknesses in internal control over financial reporting reported under Section 404 of the Sarbanes–Oxley Act (SOX). Predicting material weaknesses may be useful to investors and other financial statement users because these disclosures have adverse economic impacts on disclosing firms. Unexpected fees are significantly associated with material weaknesses reported under Section 404, even after controlling for Section 302 disclosures and other factors associated with internal control weaknesses. Unexpected fees are associated with company-level weaknesses but are not significantly associated with account-specific weaknesses, consistent with differences in the nature and severity of the two types of material weaknesses. Our results are consistent with unexpected audit fees containing information on unobserved audit costs and client control risks, which help predict future internal control weaknesses.
Accounting for Household Heterogeneity in General Equilibrium Models

The paper investigates differences in total consumption and demand according to how heterogeneity is incorporated into the model of the general equilibrium type. The sensitivity analysis for a static case with CES utilities and production functions demonstrates that the relative differences in total consumption can be considerable when a model with several heterogeneous consumer groups is compared to the one with a representative consumer. In a dynamic model, investment is proved to depend both on the production and consumption sides even in the case with one-sector production. By using the first-order optimality conditions to the multi-sector case it is shown that a model has enough capability to represent household heterogeneity to be applied for integrated assessment of carbon cycle emissions and energy demand.
A brief overview of the black-box behavioural modelling of electronic circuits for transient simulations

Transient simulations of electronic circuits in the time domain can be one of the most complex tasks that engineers encounter in the field of electronics and microelectronics due to two main problems: slow speed of SPICE transistor level circuit simulations and limited accuracy of classic techniques for improving speed of circuit simulations. The black-box approach to behavioural modelling of electronic circuits, although very challenging, is particularly interesting due to possibility of fast and accurate simulations and that is the reason why black-box modelling techniques are gaining more and more attention in industry and academic community. The goal of this professional paper is to give a brief overview of the topic, identify current state-of-the-art and give suggestions for the future research in the area of black-box behavioural modelling of electronic circuits in the time-domain.
Pathological tendons maintain sufficient aligned fibrillar structure on ultrasound tissue characterization (UTC)

Structural disorganization in the tendon is associated with tendinopathy, with little research investigating whether disorganization overwhelms the overall structural integrity of the tendon. This study investigated the mean cross‐sectional area (CSA) of aligned fibrillar structure as detected by ultrasound tissue characterization (UTC) in the pathological and normal Achilles and patellar tendons. Ninety‐one participants had their Achilles and/or patellar tendons scanned using UTC to capture a three‐dimensional image of the tendon and allow a semi‐quantification of the echopattern. The mean CSA of aligned fibrillar structure (echo type I + II) and disorganized structure (echo type III + IV) was calculated based on UTC algorithms. Each tendon was classified as either pathological or normal based solely on gray‐scale ultrasound. The mean CSA of aligned fibrillar structure was significantly greater (P ≤ 0.001) in the pathological tendon compared with the normal tendon, despite the pathological tendon containing greater amounts of disorganized structure (P ≤ 0.001). A significant relationship was observed between the mean CSA of disorganized structure and anteroposterior diameter of the Achilles (R2 = 0.587) and patellar (R2 = 0.559) tendons. This study is the first to show that pathological tendons have sufficient levels of aligned fibrillar structure. Pathological tendons may compensate for areas of disorganization by increasing in tendon thickness.
Kedudukan Pejabat Kepala Desa dalam Penyelenggaraan Pemerintahan Desa

This research was conducted to determine status and legal consequences of village head on the village management in accordance with the provisions of the village legislation. This research approach used normative juridical approach in the sense of examining norms and rules relating to issues to be discussed. Supporting data were secondary data that is obtained from library, legislation in force, and theories that exist in the literature relating to the village. The data collection is obtained by organizing a literature study (Library Research). This research result showed that the presence village head aimed to implement village government in accordance with the provisions of the legislation in force and obtained legal certainty to the community.
Site-specific Heterodimerization by Paired Class Homeodomain Proteins Mediates Selective Transcriptional Responses*

Alx4 is a paired class homeodomain protein involved in defining anterior/posterior polarity in the developing limb bud. The paired class of homeodomain proteins cooperatively bind palindromic DNA elements as homodimers or as heterodimers with other paired homeodomain proteins. Previous characterization demonstrates that the strength of the cooperativity as well as the preference for targets is dictated largely by the identity of amino acid 50 of the homeodomain. Here we compare and contrast the DNA binding properties of a glutamine 50 paired homeodomain protein, Alx4, and a lysine 50 paired homeodomain protein, Goosecoid. We demonstrate that Alx4 homodimers, Gsc homodimers, and Alx4/Gsc heterodimers each have distinct DNA binding properties, and each can discriminate between highly related palindromic elements. Using reporter gene assays, we show that Alx4 activates transcription in a site-specific manner, and that Gsc is capable of antagonizing Alx4-mediated activation only from promoter elements that support heterodimer formation. These data demonstrate that paired homeodomain proteins with different DNA binding properties are able to form heterodimeric complexes with unique DNA binding and transcriptional activities. Thus, heterodimerization regulates the DNA binding specificity of these transcription factors and may partially explain how paired homeodomain proteins direct specific developmental functions.
A comprehensive behavioral evaluation in the lithium–pilocarpine model in rats: Effects of carisbamate administration during status epilepticus

Administration of carisbamate during status epilepticus (SE) prevents the occurrence of motor seizures in the lithium–pilocarpine model and leads in a subpopulation of rats to spike‐and‐wave discharges characteristic of absence epilepsy. Widespread neuroprotection accompanied this change in seizure expression. To assess whether these carisbamate‐induced changes affected comorbidity, we used a large battery of behavioral tests in rats that had developed temporal lobe or absence‐like seizures.
Energy Intensity of GDP: A Nonlinear Estimation of Determinants in Iran

Energy intensity is a measure of the energy efficiency of a nation’s economy. Many factors influence a country’s energy intensity. In this paper, however, we note the effective factors of energy intensity and decompose it by applying Logistic Smooth Transition Regression (LSTR) in Iran during the period 1980- 2013. The main factors are the ratio of the added value of services to GDP (explaining both linear and nonlinear part of the energy intensity), the percentage of internet users, income per capita and Human Development Index (explaining nonlinear part of the energy intensity). The results indicated that the lifestyle and structural changes had a significant and considerable effect on decreasing energy intensity and that the ratio of services value-added to GDP as a transition variable caused an asymmetric behavior of energy intensity affected from explanatory variables. The most effective factor on energy intensity was Human Development Index
Design and development of therapies using chimeric antigen receptor‐expressing T cells

Investigators developed chimeric antigen receptors (CARs) for expression on T cells more than 25 years ago. When the CAR is derived from an antibody, the resultant cell should combine the desirable targeting features of an antibody (e.g. lack of requirement for major histocompatibility complex recognition, ability to recognize non‐protein antigens) with the persistence, trafficking, and effector functions of a T cell. This article describes how the past two decades have seen a crescendo of research which has now begun to translate these potential benefits into effective treatments for patients with cancer. We describe the basic design of CARs, describe how antigenic targets are selected, and the initial clinical experience with CAR‐T cells. Our review then describes our own and other investigators' work aimed at improving the function of CARs and reviews the clinical studies in hematological and solid malignancies that are beginning to exploit these approaches. Finally, we show the value of adding additional engineering features to CAR‐T cells, irrespective of their target, to render them better suited to function in the tumor environment, and discuss how the safety of these heavily modified cells may be maintained.
Modelling Welfare Loss in Iranian Electricity Market

Efficiency is an integral objective of liberalizing electricity markets, yet it is a crucial aspect as well. Experience of other countries in restructuring electricity markets shows that restructuring a market does not necessarily result in efficiency in it. Also, there is no universally agreed-upon set of rules. For these very reasons, evaluating an electricity market is vital to policy makers. Calculating welfare loss in a market measures production inefficiencies in it, and reducing welfare loss enhances production efficiencies in that market. Therefore, in this paper, we have measured welfare loss in peak hours of 2006, as the first year of the restructured market’s performance, and 2012 and have found causative factors in welfare loss in order to find possible solutions to production inefficiencies in the market. We have used an econometirc approach to test the significance of these factors to welfare loss in Iran’s restructured, payas-bid electricity market. We have found out that there is welfare loss in the market due to exercising market power by strategic firms. In addition, welfare loss in peak hours is minimum. In other words, strategic firms exercised more non-competitive behavior in hours with lower demand compared to the peak hours in 2006 and 2012. Also, we have found that structural indices, HHI and the market share ratio, display invalid results about competition in Iran’s electricity market.
Regulation of Cartilage-specific Gene Expression in Human Chondrocytes by SirT1 and Nicotinamide Phosphoribosyltransferase*

SirT1 is an NAD-dependent histone deacetylase that regulates gene expression, differentiation, development, and organism life span. Here we investigate the function of SirT1 in human chondrocytes derived from osteoarthritic patients. Elevation of SirT1 protein levels or activity in these chondrocytes led to a dramatic increase in cartilage-specific gene expression, whereas a reduction in SirT1 levels or activity significantly lowered cartilage gene expression. SirT1 associated with the cartilage-specific transcription factor Sox9, enhancing transcription from the collagen 2(α1) promoter in a Sox9-dependent fashion. Consistent with this association, SirT1 was targeted to the collagen 2(α1) enhancer and promoter, which in turn recruited the coactivators GCN5, PGC1α, and p300. This led to elevated marks of active chromatin within the promoter; that is, acetylated histone K9/K14 and histone H4K5 as well as trimethylated histone H3K4. Finally, alterations in the NAD salvage pathway enzyme nicotinamide phosphoribosyltransferase led to changes in NAD levels, SirT activity, and cartilage-specific gene expression in human chondrocytes. SirT1, nicotinamide phosphoribosyltransferase, and NAD may, therefore, provide a positive function in human cartilage by elevating expression of genes encoding cartilage extracellular matrix.
The Effects of SEA0400 on Ca2+ Transient Amplitude and Proarrhythmia Depend on the Na+/Ca2+ Exchanger Expression Level in Murine Models

Background/Objective: The cardiac Na+/Ca2+ exchanger (NCX) has been identified as a promising target to counter arrhythmia in previous studies investigating the benefit of NCX inhibition. However, the consequences of NCX inhibition have not been investigated in the setting of altered NCX expression and function, which is essential, since major cardiac diseases (heart failure/atrial fibrillation) exhibit NCX upregulation. Thus, we here investigated the effects of the NCX inhibitor SEA0400 on the Ca2+ transient amplitude and on proarrhythmia in homozygous NCX overexpressor (OE) and heterozygous NCX knockout (hetKO) mice compared to corresponding wild-types (WTOE/WThetKO). Methods/Results: Ca2+ transients of field-stimulated isolated ventricular cardiomyocytes were recorded with fluo-4-AM or indo-1-AM. SEA0400 (1 μM) significantly reduced NCX forward mode function in all mouse lines. SEA0400 (1 μM) significantly increased the amplitude of field-stimulated Ca2+ transients in WTOE, WThetKO, and hetKO, but not in OE (% of basal; OE = 98.7 ± 5.0; WTOE = 137.8 ± 5.2*; WThetKO = 126.3 ± 6.0*; hetKO = 140.6 ± 12.8*; *p < 0.05 vs. basal). SEA0400 (1 μM) significantly reduced the number of proarrhythmic spontaneous Ca2+ transients (sCR) in OE, but increased it in WTOE, WThetKO and hetKO (sCR per cell; basal/+SEA0400; OE = 12.5/3.7; WTOE = 0.2/2.4; WThetKO = 1.3/8.8; hetKO = 0.2/5.5) and induced Ca2+ overload with subsequent cell death in hetKO. Conclusion: The effects of SEA0400 on Ca2+ transient amplitude and the occurrence of spontaneous Ca2+ transients as a proxy measure for inotropy and cellular proarrhythmia depend on the NCX expression level. The antiarrhythmic effect of SEA0400 in conditions of increased NCX expression promotes the therapeutic concept of NCX inhibition in heart failure/atrial fibrillation. Conversely, in conditions of reduced NCX expression, SEA0400 suppressed the NCX function below a critical level leading to adverse Ca2+ accumulation as reflected by an increase in Ca2+ transient amplitude, proarrhythmia and cell death. Thus, the remaining NCX function under inhibition may be a critical factor determining the inotropic and antiarrhythmic efficacy of SEA0400.
A connectivity model as a potential tool for smart specialization strategies

ABSTRACT The article contributes to the smart specialization literature by presenting a new approach, connectivity analysis, where Triple Helix (TH) relations (involving universities, companies and government) are at the centre of the entrepreneurial discovery process. Relations between helices may be seen, from the point of departure of proximity, as preconditions of connectivity, or interaction, measured through expectations and experiences. This offers potential solution to two limitations of proximity approach: its static nature and narrow focus on dyadic relationships. The connectivity analysis reveals the extent of mutual expectations, as well as tensions, or gaps. Based on this analysis, the article presents a policy model that is used to map structures of networks and gaps between TH actors. It may also identify strengths, weaknesses and problems. This analysis is used as input to structured dialogues between actors in leading positions in the TH and in smart specialization policy-making and implementation. This approach may lead to policy interventions supporting entrepreneurial discoveries. The model has been developed in partnership with researchers and the Regional Council of Ostrobothnia. The article also presents this case study and demonstrates the use of the connectivity model in practice.
Rheumatoid arthritis and cancer risk[BULLET OPERATOR]results from the Greek European prospective investigation into cancer and nutrition cohort

To investigate the relative risk of cancer development in rheumatoid arthritis (RA) patients in Greece after taking into consideration treatment modalities. The present analysis used data on the medical history of 26 331 participants in the Greek arm of the European Prospective Investigation into Cancer and Nutrition that were collected at enrollment and thereafter during active follow-up. A history of RA and of drug treatment for the disease, as reported at baseline examination, was linked to cases of cancer reported during follow-up. A total of 91 (9.9%) patients with RA developed a cancer compared with 1542 (6.1%) patients without RA. The overall hazard ratios of all cancers increased 25% [95% confidence interval (CI): 1–54] among participants with prevalent RA, and almost all the site-specific incident cancer sites considered had rate ratios above unity. In terms of the contribution of RA medication, the hazard ratios of patients treated with salicylates was close to unity (1.07, 95% CI: 0.69–1.65), whereas those who were not treated with salicylates had a 31% (95% CI: 3–67) increased risk for cancer incidence compared with those without RA at baseline. RA patients have excess cancer risk because of either underlying complex disease pathways or treatment agents targeting immune function. Administration of salicylates appears to reduce the risk of developing malignancies.
Statistical Applications in Genetics and Molecular Biology A Multilocus Model for Constructing a Linkage Disequilibrium Map in Human Populations

The extent and pattern of linkage disequilibrium (LD) determine the feasibility of association studies to map genes that underlie complex traits. Here we present a statistical algorithm for constructing a joint linkage-linkage disequilibrium map by simultaneously estimating the recombination fraction and linkage disequilibrium between different molecular markers in a natural human population. This algorithm was devised with a set of random unrelated families, each including a father, a mother and a varying number of offspring, sampled from a population at Hardy-Weinberg equilibrium. A two-level hierarchical mixture model framework was built, in which the likelihood of genotype data for the parents was formulated in terms of linkage disequilibrium at an upper level, whereas the likelihood of genetic transmission from the parents to offspring formulated in terms of the recombination fraction at a lower level. The EM algorithm was implemented to obtain a closed system of maximum likelihood estimates of marker cosegregation and co-transmission. The model allows a number of testable hypotheses about population genetic parameters, opening a broad gateway to understand the genetic structure and dynamics of an outcrossing population under natural selection. The new strategy will provide a platform for studying the genetic control of inherited diseases in which genetic material is accurately copied before being passed onto the offspring from a parent.
Multimodal User Interfaces to Improve Social Integration of Elderly and Mobility Impaired

Technologies for Human-Computer Interaction (HCI) and Communication have evolved tremendously over the past decades. However, citizens such as mobility impaired or elderly or others, still face many difficulties interacting with communication services, either due to HCI issues or intrinsic design problems with the services. In this paper we start by presenting the results of two user studies, the first one conducted with a group of mobility impaired users, comprising paraplegic and quadriplegic individuals; and the second one with elderly. The study participants carried out a set of tasks with a multimodal (speech, touch, gesture, keyboard and mouse) and multi-platform (mobile, desktop) system, offering an integrated access to communication and entertainment services, such as email, agenda, conferencing, instant messaging and social media, referred to as LHC - Living Home Center. The system was designed to take into account the requirements captured from these users, with the objective of evaluating if the adoption of multimodal interfaces for audio-visual communication and social media services, could improve the interaction with such services. Our study revealed that a multimodal prototype system, offering natural interaction modalities, especially supporting speech and touch, can in fact improve access to the presented services, contributing to the reduction of social isolation of mobility impaired, as well as elderly, and improving their digital inclusion.
Inhibition of p34cdc2 dephosphorylation in DNA damage‐ and topoisomerase II inactivation‐induced G2 arrests in HL‐60 cells

Doxorubicin induces DNA breakage by stabilizing a cleavable topoisomerase II–DNA complex. In contrast, topoisomerase II catalytic inhibitor ICRF‐193 and uncoupling inhibitor aclarubicin interfere with the cleavable complex formation. We analysed combination effects of these drugs using two‐dimensional flow cytometry of DNA content and the terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end‐labelling assay. Both ICRF‐193 and aclarubicin attenuated the cytotoxic effect of doxorubicin on HL‐60 cells (85% and 46% maximum reduction, respectively), which suggested that doxorubicin exerts its cytotoxic effect at least partially through the topoisomerase II‐dependent DNA cleavage. Doxorubicin and ICRF‐193 both induced G2 arrest in HL‐60 cells, by which they may have reduced the cytotoxic effect of vincristine. Indeed, although ICRF‐193 inhibited doxorubicin‐induced apoptosis, ICRF‐193 and doxorubicin cooperated in arresting HL‐60 cells at G2 phase. These results indicated that G2 arrest was caused not only by DNA damage but also through a DNA damage‐free, topoisomerase II inactivation‐induced pathway. Western blot analysis showed that both types of G2 arrest were mediated by the inhibition of p34cdc2 dephosphorylation.