Miracle-dz/UniFAR-FTUs huggingface dataset:
Misfolded proteins inhibit proliferation and promote stress‐induced death in SV40‐transformed mammalian cells

Protein misfolding is implicated in neurodegenerative diseases and occurs in aging. However, the contribution of the misfolded ensembles to toxicity remains largely unknown. Here we introduce 2 primate cell models of destabilized proteins devoid of specific cellular functions and interactors, as bona fide mis‐folded proteins, allowing us to isolate the gain‐of‐function of non‐native structures. Both GFP‐degron and a mutant chloramphenicol‐acetyltransferase fused to GFP (GFP‐Δ9CAT) form perinuclear aggregates, are degraded by the proteasome, and colocalize with and induce the chaperone Hsp70 (HSPA1A/B) in COS‐7 cells. We find that misfolded proteins neither significantly compromise chaperone‐mediated folding capacity nor induce cell death. However, they do induce growth arrest in cells that are unable to degrade them and promote stress‐induced death upon proteasome inhibition by MG‐132 and heat shock. Finally, we show that overexpression of all heat‐shock factor‐1 (HSF1) and Hsp70 proteins, as well as wild‐type and deacetylase‐deficient (H363Y) SIRT1, rescue survival upon stress, implying a noncatalytic action of SIRT1 in response to protein misfolding. Our study establishes a novel model and extends our knowledge on the mechanism of the function‐independent proteotoxicity of misfolded proteins in dividing cells. —Arslan, M. A. , Chikina, M. , Csermely, P., Sőti, C. Misfolded proteins inhibit proliferation and promote stress‐induced death in SV40‐transformed mammalian cells. FASEB J. 26, 766–777 (2012). www.fasebj. org
The Psychological Consequences of Tardive Dyskinesia the Effect of Drug-Induced Parkinsonism and the Topography of the Dyskinetic Movements

The effect of drug-induced Parkinsonism and of the topography of the dyskinetic movements on the psychological consequences of tardive dyskinesia was assessed in 20 schizophrenic subjects and 20 non-dyskinetic schizophrenic controls matched for age, sex, the presence of anticholinergic medication, and the presence and severity of drug-induced Parkinsonism. Limb–truncal subscale scores but not orofacial scores had a significant correlation with cognitive impairment and with negative symptoms. Drug-induced Parkinsonism was found to be a powerful confounding variable.
From Negative to Positive Peace: The Case of Bosnia and Hercegovina

This article, which is grounded in qualitative interview data, takes as its starting point the contention that war crimes tribunals can aid reconciliation, and more specifically the claim made by the International Criminal Tribunal for the former Yugoslavia (ICTY) that its work is contributing to reconciliation in the region. Focusing on Bosnia and Hercegovina (BiH), the first question that it seeks to answer is not whether the ICTY has positively impacted on reconciliation, but rather the more immediate question of whether reconciliation actually exists in BiH. Defining reconciliation as the restoration and repair of relationships and as the acknowledgement of war crimes and responsibility, it argues that there is no reconciliation in present-day BiH. There is only negative peace—an absence of conflict. The second crucial question that this article explores, therefore, is whether and how this negative peace can be developed into positive peace characterized by reconciliation. Emphasizing two critical obstacles to any reconciliation process in BiH, namely insufficient contact between interethnic groups and the existence of denial and competing truths, it identifies three important measures to address these. These are the abolition of the divisive “two schools under one roof” education system, the replacement of the Dayton Peace Accords (DPA) with a constitutional structure that encourages interethnic contact rather than separation, and the creation of a truth and reconciliation commission (TRC). On the issue of whether the ICTY can itself contribute to reconciliation in BiH, the article concludes that while retributive justice is an important mechanism in postconflict societies, the difficulties and challenges that the ICTY faces in BiH underscore the limitations of criminal trials and the imperative of a multifaceted approach to reconciliation combining different transitional justice elements.
Oxidative stress in patients with endodontic pathologies

Background Apical periodontitis (AP) is an inflammatory disease affecting periradicular tissues. It is a widespread condition but its etiopathogenetic mechanisms have not been completely elucidated and the current treatment options are not always successful. Purpose To compare oxidative stress (OxS) levels in the saliva and the endodontium (root canal [RC] contents) in patients with different endodontic pathologies and in endodontically healthy subjects. Patients and methods The study group of this comparison study included 22 subjects with primary chronic apical periodontitis (pCAP), 26 with posttreatment or secondary chronic apical periodontitis (sCAP), eight with acute periapical abscess, 13 with irreversible pulpitis, and 17 healthy controls. Resting saliva samples were collected before clinical treatment. Pulp samples (remnants of the pulp, tooth tissue, and/or previous root filling material) were collected under strict aseptic conditions using the Hedström file. The samples were frozen to −80°C until analysis. OxS markers (myeloperoxidase [MPO], oxidative stress index [OSI], 8-isoprostanes [8-EPI]) were detected in the saliva and the endodontium. Results The highest MPO and 8-EPI levels were seen in pCAP and pulpitis, while the highest levels of OSI were seen in pCAP and abscess patients, as well as the saliva of sCAP patients. Controls showed the lowest OxS levels in both RC contents and saliva. Significant positive correlations between OxS markers, periapical index, and pain were revealed. Patients with pain had significantly higher OxS levels in both the endodontium (MPO median 27.9 vs 72.6 ng/mg protein, p=0.004; OSI 6.0 vs 10.4, p<0.001; 8-EPI 50.0 vs 75.0 pg/mL, p<0.001) and saliva (MPO 34.2 vs 117.5 ng/mg protein, p<0.001; 8-EPI 50.0 vs 112.8 pg/mL, p<0.001) compared to pain-free subjects. Conclusion OxS is an important pathomechanism in endodontic pathologies that is evident at both the local (RC contents) and systemic (saliva) level. OxS is significantly associated with dental pain and bone destruction.
Android Code Protection via Obfuscation Techniques: Past, Present and Future Directions

Mobile devices have become ubiquitous due to centralization of private user information, contacts, messages and multiple sensors. Google Android, an open-source mobile Operating System (OS), is currently the market leader. Android popularity has motivated the malware authors to employ set of cyber attacks leveraging code obfuscation techniques. Obfuscation is an action that modifies an application (app) code, preserving the original semantics and functionality to evade anti-malware. Code obfuscation is a contentious issue. Theoretical code analysis techniques indicate that, attaining a verifiable and secure obfuscation is impossible. However, obfuscation tools and techniques are popular both among malware developers (to evade anti-malware) and commercial software developers (protect intellectual rights). We conducted a survey to uncover answers to concrete and relevant questions concerning Android code obfuscation and protection techniques. The purpose of this paper is to review code obfuscation and code protection practices, and evaluate efficacy of existing code de-obfuscation tools. In particular, we discuss Android code obfuscation methods, custom app protection techniques, and various de-obfuscation methods. Furthermore, we review and analyse the obfuscation techniques used by malware authors to evade analysis efforts. We believe that, there is a need to investigate efficiency of the defense techniques used for code protection. This survey would be beneficial to the researchers and practitioners, to understand obfuscation and de-obfuscation techniques to propose novel solutions on Android.
Usual and Unusual Histologic Patterns of High Gleason Score 8 to 10 Adenocarcinoma of the Prostate in Needle Biopsy Tissue

High Gleason score 8 to 10 adenocarcinoma is the most aggressive and potentially lethal form of prostate cancer. The 2005 International Society of Urological Pathology (ISUP)-modified Gleason grading scheme defines several gland arrangements of high Gleason grade patterns 4 and 5. The aim of this investigation was to quantitate the frequency of the ISUP-defined high Gleason grade patterns in needle biopsy tissue, to determine the common admixtures and to characterize patterns not presented in the 2005 ISUP report. For patients who underwent radical prostatectomy, we analyzed for association of specific high-grade patterns in needle biopsy with extraprostatic extension in radical prostatectomy tissues. A total of 268 prostate needle biopsy cases with Gleason score of 8 to 10 were examined. A mean of 3.6 patterns (range, 1 to 8) were identified per case and only 12% of cases had a pure single pattern. Ill-defined glands with poorly formed lumina (at 57%) and fused microacinar glands (at 53%) comprised the predominant and most frequently admixed patterns. Single cells and single signet ring cells were present in 53% and 31% of cases, respectively. Additional patterns in order of frequency included cords (35%), cribriform glands (25%), sheets of cells (19%), chains (4%), glomeruloid (3%), comedonecrosis (2%), and hypernephromatoid (1 case=0.3%). Gleason score 8 to 10 carcinomas are typically extensive in needle core tissue, with a mean of 4.4 positive cores (range, 1 to 15 cores) per case. Only 14 cases (5%) had high-grade minimal carcinoma measuring <1 mm in needle core tissue. Gleason grade patterns not described in the 2005 ISUP report include single file growth, solid cylinders, and nested patterns. The single file pattern was present in 40% of cases, and the small solid nested pattern was detected in 24% of cases. One case displayed solid cylinders. Only the single file pattern was associated with extraprostatic extension at radical prostatectomy (P=0.005). These results show that the 2005 ISUP-defined patterns of high Gleason score 8 to 10 prostatic adenocarcinoma can be stratified on the basis of frequency of occurrence in needle biopsy tissue. Three patterns not defined in the 2005 ISUP scheme have been characterized, including single file, nested, and solid cylinder arrangements. As aggressive and potentially lethal prostate cancer is most often of Gleason score 8 to 10, it is important for diagnostic recognition purposes to be aware of the frequency of various patterns encountered in high Gleason score 8 to 10 adenocarcinomas, the types of pattern admixtures, and the histomorphologic presentation of unusual patterns. We propose that Gleason grade assignments should incorporate single file, solid nested, and solid cylinder arrangements as high-grade pattern 5 because of the absence of glandular luminal space formation.
The endocannabinoid transport inhibitor AM404 differentially modulates recognition memory in rats depending on environmental aversiveness

Cannabinoid compounds may influence both emotional and cognitive processes depending on the level of environmental aversiveness at the time of drug administration. However, the mechanisms responsible for these responses remain to be elucidated. The present experiments investigated the effects induced by the endocannabinoid transport inhibitor AM404 (0.5–5 mg/kg, i.p.) on both emotional and cognitive performances of rats tested in a Spatial Open Field task and subjected to different experimental settings, named High Arousal (HA) and Low Arousal (LA) conditions. The two different experimental conditions influenced emotional reactivity independently of drug administration. Indeed, vehicle-treated rats exposed to the LA condition spent more time in the center of the arena than vehicle-treated rats exposed to the HA context. Conversely, the different arousal conditions did not affect the cognitive performances of vehicle-treated animals such as the capability to discriminate a spatial displacement of the objects or an object substitution. AM404 administration did not alter locomotor activity or emotional behavior of animals exposed to both environmental conditions. Interestingly, AM404 administration influenced the cognitive parameters depending on the level of emotional arousal: it impaired the capability of rats exposed to the HA condition to recognize a novel object while it did not induce any impairing effect in rats exposed to the LA condition. These findings suggest that drugs enhancing endocannabinoid signaling induce different effects on recognition memory performance depending on the level of emotional arousal induced by the environmental conditions.
Formation of Ti–Zr–Cu–Ni bulk metallic glasses

Formation of bulk metallic glass in quaternary Ti–Zr–Cu–Ni alloys by relatively slow cooling from the melt is reported. Thick strips of metallic glass were obtained by the method of metal mold casting. The glass forming ability of the quaternary alloys exceeds that of binary or ternary alloys containing the same elements due to the complexity of the system. The best glass forming alloys such as Ti34Zr11Cu47Ni8 can be cast to at least 4-mm-thick amorphous strips. The critical cooling rate for glass formation is of the order of 250 K/s or less, at least two orders of magnitude lower than that of the best ternary alloys. The glass transition, crystallization, and melting behavior of the alloys were studied by differential scanning calorimetry. The amorphous alloys exhibit a significant undercooled liquid region between the glass transition and first crystallization event. The glass forming ability of these alloys, as determined by the critical cooling rate, exceeds what is expected based on the reduced glass transition temperature. It is also found that the glass forming ability for alloys of similar reduced glass transition temperature can differ by two orders of magnitude as defined by critical cooling rates. The origins of the difference in glass forming ability of the alloys are discussed. It is found that when large composition redistribution accompanies crystallization, glass formation is enhanced. The excellent glass forming ability of alloys such as Ti34Zr11Cu47Ni8 is a result of simultaneously minimizing the nucleation rate of the competing crystalline phases. The ternary/quaternary Laves phase (MgZn2 type) shows the greatest ease of nucleation and plays a key role in determining the optimum compositions for glass formation.
Intellectual Disabilities and Socioeconomic Inequalities in Health: An Overview of Research.

Background There is an enduring association between socioeconomic position and health, both over time and across major causes of death. Children and adults with intellectual disabilities are disproportionately represented among the poorer and less healthy sections of the population. But research on health inequalities, and on the broader societal influences on health, has yet to be integrated into perspectives and policy for people with intellectual disabilities. Methods The paper reviews evidence on the patterns and causes of socioeconomic inequalities in health. Results It points to evidence that socioeconomic position is the fundamental determinant of health, drawing on longitudinal studies to highlight how it exerts its influence on health from before birth and across the lifecourse. The factors shaping an individual's socioeconomic position are also discussed. Conclusions The paper concludes by identifying research and policy challenges.
Novel insights into the molecular pathogenesis of CYP4V2-associated Bietti's retinal dystrophy

Bietti's crystalline dystrophy (BCD) is a rare, autosomal recessive retinal degenerative disease associated with mutations in CYP4V2. In this study, we describe the genetic and clinical findings in 19 unrelated BCD patients recruited from five international retinal dystrophy clinics. Patients underwent ophthalmic examinations and were screened for CYP4V2 mutations by Sanger sequencing and quantitative polymerase chain reaction (qPCR) copy number variation screening. Eight CYP4V2 mutations were found in 10/19 patients, including three patients in whom only monoallelic mutations were detected. Four novel mutations were identified: c.604G>A; p.(Glu202Lys), c.242C>G; p.(Thr81Arg), c.604+4A>G; p.(? ), and c.1249dup; p.(Thr417Asnfs*2). In addition, we identified a heterozygous paternally inherited genomic deletion of at least 3.8 Mb, encompassing the complete CYP4V2 gene and several other genes, which is novel. Clinically, patients demonstrated phenotypic variability, predominantly showing choroidal sclerosis, attenuated vessels, and crystalline deposits of varying degrees of severity. To our knowledge, our study reports the first heterozygous CYP4V2 deletion and hence a novel mutational mechanism underlying BCD. Our results emphasize the importance of copy number screening in BCD. Finally, the identification of CYP4V2‐negative patients with indistinguishable phenotypes from CYP4V2‐positive patients might suggest the presence of mutations outside the coding regions of CYP4V2, or locus heterogeneity, which is unreported so far.
Anti-Inflammatory Activity in Colon Models Is Derived from Δ9-Tetrahydrocannabinolic Acid That Interacts with Additional Compounds in Cannabis Extracts

Abstract Introduction: Inflammatory bowel diseases (IBDs) include Crohn's disease, and ulcerative colitis. Cannabis sativa preparations have beneficial effects for IBD patients. However, C. sativa extracts contain hundreds of compounds. Although there is much knowledge of the activity of different cannabinoids and their receptor agonists or antagonists, the cytotoxic and anti-inflammatory activity of whole C. sativa extracts has never been characterized in detail with in vitro and ex vivo colon models. Material and Methods: The anti-inflammatory activity of C. sativa extracts was studied on three lines of epithelial cells and on colon tissue. C. sativa flowers were extracted with ethanol, enzyme-linked immunosorbent assay was used to determine the level of interleukin-8 in colon cells and tissue biopsies, chemical analysis was performed using high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance and gene expression was determined by quantitative real-time PCR. Results: The anti-inflammatory activity of Cannabis extracts derives from D9-tetrahydrocannabinolic acid (THCA) present in fraction 7 (F7) of the extract. However, all fractions of C. sativa at a certain combination of concentrations have a significant increased cytotoxic activity. GPR55 receptor antagonist significantly reduces the anti-inflammatory activity of F7, whereas cannabinoid type 2 receptor antagonist significantly increases HCT116 cell proliferation. Also, cannabidiol (CBD) shows dose dependent cytotoxic activity, whereas anti-inflammatory activity was found only for the low concentration of CBD, and in a bell-shaped rather than dose-dependent manner. Activity of the extract and active fraction was verified on colon tissues taken from IBD patients, and was shown to suppress cyclooxygenase-2 (COX2) and metalloproteinase-9 (MMP9) gene expression in both cell culture and colon tissue. Conclusions: It is suggested that the anti-inflammatory activity of Cannabis extracts on colon epithelial cells derives from a fraction of the extract that contains THCA, and is mediated, at least partially, via GPR55 receptor. The cytotoxic activity of the C. sativa extract was increased by combining all fractions at a certain combination of concentrations and was partially affected by CB2 receptor antagonist that increased cell proliferation. It is suggested that in a nonpsychoactive treatment for IBD, THCA should be used rather than CBD.
Longitudinal Associations among Undergraduates' Research Experience, Self-Efficacy, and Identity.

Prior research shows that undergraduates tend to identify more strongly with the field of science after participating in scientific research. However, mediators that might account for this association are not well understood. In the current study, we propose that science self-efficacy may serve this mediational function. Specifically, data from a 2-year longitudinal study were used to test a model in which science self-efficacy was expected to mediate the association between research involvement and identity as a scientist. The ethnically diverse sample included 251 undergraduates who were recruited from colleges and universities across the United States. The hypothesized mediation model was tested with a cross-lagged panel analysis. As expected, greater levels of research experience at Time 1 predicted higher identity as a scientist at Time 3, and this association was mediated by science self-efficacy at Time 2. Exploratory analyses testing for ethnic and gender differences in the model suggested that the associations in the model were similar for undergraduates from diverse backgrounds. From a theoretical standpoint, the current study provides novel insight into how research experience, efficacy, and identity relate to one another over time. Applied implications center on the importance of involving undergraduates in research that has the potential to bolster their science self-efficacy. © 2015 Wiley Periodicals, Inc. J Res Sci Teach 52: 847–867, 2015.
A Study of the Attitudes, Motives, and Strategies of University Foreign Language Students and Their Disposition to Authentic Oral and Written Input

A MAJOR AREA OF SECOND LANGUAGE (SL) acquisition research is the role played by learner variables in the process of learning a second language. ' The focus of interest is on the complex relationship between learner characteristics, their specific language learning behaviors or strategies, and, of course, the ultimate success of these strategies in language learning. Learner characteristics in the social and affective domains in particular are widely regarded as profoundly influencing outcome by virtue of their association with language acquisition behavior. The pioneering work of Gardner and Lambert (13, 14) brought motivation and other attitudinal/affective variables to the forefront of research. Krashen's Monitor
Parenting and Child Characteristics in the Prediction of Shame in Early and Middle Childhood

We examined individual differences in shame responding in early childhood and predictive relations with shame proneness in middle childhood. Child shame responding, parental shaming, and child temperamental inhibition were assessed at Time 1 (n = 225, aged 3–4 years), shame responding was reassessed at Time 2 (n = 199, aged 5–7 years), and shame proneness was assessed at Time 3 (n = 162, aged 7–9 years). Shame responding was assessed from emotionexpressive reactions to failure, parental shaming from self-reports and spouse reports, temperamental inhibition from mother and father ratings, and shame proneness from hypothetical scenarios. Girls showed more shame than boys by school age. Increased shame responding between preschool age and school age was predicted, for girls, from lower inhibition or higher mother shaming and, for boys, from higher mother shaming if boys were highly inhibited. Shame responding at preschool age predicted higher or lower shame proneness in middle childhood conditional on gender and parenting.