Miracle-dz/UniFAR-FTUs huggingface dataset:
The Rac1 C-terminal Polybasic Region Regulates the Nuclear Localization and Protein Degradation of Rac1*

We observed evolutionary conservation of canonical nuclear localization signal sequences (K(K/R)X(K/R)) in the C-terminal polybasic regions (PBRs) of some Rac and Rho isoforms. Canonical D-box sequences (RXXL), which target proteins for proteasome-mediated degradation, are also evolutionarily conserved near the PBRs of these small GTPases. We show that the Rac1 PBR (PVKKRKRK) promotes Rac1 nuclear accumulation, whereas the RhoA PBR (RRGKKKSG) keeps RhoA in the cytoplasm. A mutant Rac1 protein named Rac1 (pbrRhoA), in which the RhoA PBR replaces the Rac1 PBR, has greater cytoplasmic localization, enhanced resistance to proteasome-mediated degradation, and higher protein levels than Rac1. Mutating the D-box by substituting alanines at amino acids 174 and 177 significantly increases the protein levels of Rac1 but not Rac1(pbrRhoA). These results suggest that Rac1 (pbrRhoA) is more resistant than Rac1 to proteasome-mediated degradative pathways involving the D-box. The cytoplasmic localization of Rac1(pbrRhoA) provides the most obvious reason for its resistance to proteasome-mediated degradation, because we show that Rac1(pbrRhoA) does not greatly differ from Rac1 in its ability to stimulate membrane ruffling or to interact with SmgGDS and IQGAP1-calmodulin complexes. These findings support the model that nuclear localization signal sequences in the PBR direct Rac1 to the nucleus, where Rac1 participates in signaling pathways that ultimately target it for degradation.
Altered oxidative status and integrin expression in cyclosporine A-treated oral epithelial cells

Abstract Background and objective: Cyclosporine A (CsA) is an immunosuppressive agent administered to transplant patients. A well-known reported oral side effect of CsA consumption is gingival overgrowth (GO). Changes in the expression of integrins occurring in the gingiva following CsA treatment have been reported but these reports are mainly concerned with the connective tissue of the gingiva. In this study we targeted the alterations in the oral epithelium using KB cells, an oral epithelial cell line. Methods: Cultured oral epithelial cells were treated with increasing concentrations of CsA (0.1, 1 and 10 µg/mL) and the molecular changes involving antioxidant enzymes [glutathione peroxidase (GPx) and glutathione reductase (GR)] and the level of reactive oxygen species (ROS) were measured. Quantitative real-time PCR was used to assess the expression of selected integrins (α2, α5 and β1). Results: At CsA concentration above 0.1 µg/mL GPx demonstrated an increase in activity while GR activity and the level of reduced glutathione were diminished (p < 0.05). α5 and β1 integrin were downregulated at all treatment concentrations of CsA while α2 integrin presented this effect at concentrations above 1 µg/mL (p < 0.05). Conclusion: The results suggest a possible role for oxidative stress and the altered expression of integrins in the pathology of CsA-induced gingival overgrowth.
Towards a Dataset for Human Computer Communication via Grounded Language Acquisition

The Natural Language Processing, Artiﬁcial Intelligence, and Robotics ﬁelds have made signiﬁcant progress towards developing robust component technologies (speech recognition/synthesis, machine translation, image recognition); advanced inference mechanisms that accommodate uncertainty and noise; and autonomous driving systems that operate seamlessly on our roads. In spite of this, we do not yet know how to talk to the machines we build or have them speak to us in natural language; how to make them smarter via simple, natural language instructions; how to understand what they are about to do; or how to work with them collaboratively towards accomplishing some joint goal. In this paper, we discuss our work towards building a dataset that enables an empirical approach to studying the relation between natural language, actions, and plans; and introduce a problem formulation that allows us to take meaningful steps towards addressing the open problems listed above.
Zeolite-based Impedimetric Gas Sensor Device in Low-cost Technology for Hydrocarbon Gas Detection

Due to increasing environmental concerns the need for inexpensive selective gas sensors is increasing. This work deals with transferring a novel zeolite-based impedimetric hydrocarbon gas sensor principle, which has been originally manufactured in a costly combination of photolithography, thin-film processes, and thick-film processes to a low-cost technology comprising only thick-film processes and one electroplating step. The sensing effect is based on a thin chromium oxide layer between the interdigital electrodes and a Pt-loaded ZSM-5 zeolite film. When hydrocarbons are present in the sensor ambient, the electrical sensor impedance increases strongly and selectively. In the present work, the chromium oxide film is electroplated on Au screen-printed interdigital electrodes and then oxidized to Cr2O3. The electrode area is covered with the screen-printed zeolite. The sensor device is self-heated utilizing a planar platinum heater on the backside. The best sensor performance is obtained at a frequency of 3 Hz at around 350 °C. The good selectivity of the original sensor setup could be confirmed, but a strong cross-sensitivity to ammonia occurs, which might prohibit its original intention for use in automotive exhausts.
A mechanism-based pharmacokinetic-enzyme model for cyclophosphamide autoinduction in breast cancer patients.

AIMS This study investigated the pharmacokinetics of cyclophosphamide (CP) and its main metabolite 4-hydroxycyclophosphamide (4-OH-CP) in patients with breast cancer undergoing high dose chemotherapy prior to autologous stem cell transplantation. An enzyme turn-over model was also developed to study the time course of cyclophosphamide induction. METHODS Fourteen patients received a combination of CP (6 g m-2 ), thiotepum (500 mg m-2 ) and carboplatin (800 mg m-2 ) as a 96 h infusion. Plasma concentrations of CP and 4-OH-CP were determined with h.p.l.c. and a pharmacokinetic and enzyme turn-over model applied to data using NONMEM. RESULTS CP plasma concentrations were described by a two-compartment model with a noninducible and an inducible pathway, the latter forming 4-OH-CP. In the final enzyme model, CP affects the amount of enzymes by increasing the enzyme production rate. CP concentrations decreased during the infusion with no subsequent change in 4-OH-CP concentrations. CP inducible and noninducible clearance were estimated to 1.76 l h-1 (90% C.I. 0.92-2.58) and 1.14 l h-1 (0.31-1.85), respectively. The induction resulted in an approximately doubled CP clearance through the inducible pathway at the end of treatment. The model predicted the enzyme turn-over half-life to be 24 h. CONCLUSIONS The presented mechanism-based enzyme induction model where the pharmacokinetics of the inducer and the enzyme pool counterbalance each other successfully described CP autoinduction. It is reasonable to believe that CP affects its own elimination by increasing the enzyme production rate and thereby increasing the amount of enzyme by which CP is eliminated.
Dynamic Trial-by-Trial Recoding of Task-Set Representations in the Frontoparietal Cortex Mediates Behavioral Flexibility

Cognitive flexibility forms the core of the extraordinary ability of humans to adapt, but the precise neural mechanisms underlying our ability to nimbly shift between task sets remain poorly understood. Recent functional magnetic resonance imaging (fMRI) studies employing multivoxel pattern analysis (MVPA) have shown that a currently relevant task set can be decoded from activity patterns in the frontoparietal cortex, but whether these regions support the dynamic transformation of task sets from trial to trial is not clear. Here, we combined a cued task-switching protocol with human (both sexes) fMRI, and harnessed representational similarity analysis (RSA) to facilitate a novel assessment of trial-by-trial changes in neural task-set representations. We first used MVPA to define task-sensitive frontoparietal and visual regions and found that neural task-set representations on switch trials are less stably encoded than on repeat trials. We then exploited RSA to show that the neural representational pattern dissimilarity across consecutive trials is greater for switch trials than for repeat trials, and that the degree of this pattern dissimilarity predicts behavior. Moreover, the overall neural pattern of representational dissimilarities followed from the assumption that repeating sets, compared with switching sets, results in stronger neural task representations. Finally, when moving from cue to target phase within a trial, pattern dissimilarities tracked the transformation from previous-trial task representations to the currently relevant set. These results provide neural evidence for the longstanding assumptions of an effortful task-set reconfiguration process hampered by task-set inertia, and they demonstrate that frontoparietal and stimulus processing regions support “dynamic adaptive coding,” flexibly representing changing task sets in a trial-by-trial fashion. SIGNIFICANCE STATEMENT Humans can fluently switch between different tasks, reflecting an ability to dynamically configure “task sets,” rule representations that link stimuli to appropriate responses. Recent studies show that neural signals in frontal and parietal brain regions can tell us which of two tasks a person is currently performing. However, it is not known whether these regions are also involved in dynamically reconfiguring task-set representations when switching between tasks. Here we measured human brain activity during task switching and tracked the similarity of neural task-set representations from trial to trial. We show that frontal and parietal brain regions flexibly recode changing task sets in a trial-by-trial fashion, and that task-set similarity over consecutive trials predicts behavior.
Face identification across different poses and illuminations with a 3D morphable model

We present a novel approach for recognizing faces in images taken from different directions and under different illumination. The method is based on a 3D morphable face model that encodes shape and texture in terms of model parameters, and an algorithm that recovers these parameters from a single image of a face. For face identification, we use the shape and texture parameters of the model that are separated from imaging parameters, such as pose and illumination. In addition to the identity, the system provides a measure of confidence. We report experimental results for more than 4000 images from the publicly available CMU-PIE database.
Which alcohol use disorder criteria contribute to the association of ADH1B with alcohol dependence?

Although alcohol dependence (AD) is approximately 50% heritable, little is known about how specific genetic loci affect AD risk. In a genome‐wide association study (GWAS), we identified highly significant associations between two population‐specific functional variants in the alcohol dehydrogenase 1B gene (ADH1B) and AD in African‐Americans (AAs; rs2066702) and European‐Americans (EAs; rs1229984). In the current study, we determined which specific diagnostic criteria contributed to the observed associations of ADH1B SNPs with AD. Our analysis included both the DSM‐IV and DSM‐5 diagnostic systems. We also investigated the relationship of ADH1B variants to the maximum number of drinks consumed in a 24‐hour period (MaxDrinks), a presumed intermediate phenotype of AD. We found that, although all criteria made strong individual contributions to the associations, the largest contributions came from those reflecting neuroadaptation: tolerance (rs2066702) and withdrawal (rs1229984). Overall, evidence for association with DSM‐5 criteria was slightly stronger than for DSM‐IV criteria. For rs2066702, results were similar for DSM‐IV and DSM‐5 criteria. However, the most significant DSM‐5 criterion associated with rs1229984 was alcohol‐related social/interpersonal problems. Both ADH1B variants were associated with MaxDrinks, a measure of innate tolerance, and MaxDrinks mediated the associations between ADH1B and alcohol outcomes. We replicated the findings for rs2066702 and tolerance in an independent sample of AAs. Taken together, these results suggest that variation in ADH1B affects the adaptation to heavy drinking, highlighting population‐specific differences in genetic risk for AUD. They also suggest that the revisions reflected in DSM‐5 AUD may enhance the utility of that diagnosis for gene finding.
Your privacy is assured - of being disturbed: websites with and without privacy seals

Privacy seals were developed to address concerns about online privacy. However, seals are widely misinterpreted by consumers as privacy protection. This research assessed how well privacy policies matched the standards promised by the seal authorities and compared the privacy protection practices of participating and non-participating sites. Privacy policy statements were interpreted as a form of persuasive communication that attempts to minimize the risks of providing personal information while emphasizing the benefits of personal disclosure. There were few differences in the privacy practices between seal authorities: TRUSTe and BBBOnLine participants offered about the same degree of privacy protection assurances and they were equal with regard to the amount or depth of personal information they requested. Notably, unsealed sites offered nearly equal privacy assurances and made fewer personal information requests than the sealed sites. However, seal program participants did provide superior access to information and assurances of data security.
Graph Theoretical Analysis of Functional Brain Networks: Test-Retest Evaluation on Short- and Long-Term Resting-State Functional MRI Data

Graph-based computational network analysis has proven a powerful tool to quantitatively characterize functional architectures of the brain. However, the test-retest (TRT) reliability of graph metrics of functional networks has not been systematically examined. Here, we investigated TRT reliability of topological metrics of functional brain networks derived from resting-state functional magnetic resonance imaging data. Specifically, we evaluated both short-term (<1 hour apart) and long-term (>5 months apart) TRT reliability for 12 global and 6 local nodal network metrics. We found that reliability of global network metrics was overall low, threshold-sensitive and dependent on several factors of scanning time interval (TI, long-term>short-term), network membership (NM, networks excluding negative correlations>networks including negative correlations) and network type (NT, binarized networks>weighted networks). The dependence was modulated by another factor of node definition (ND) strategy. The local nodal reliability exhibited large variability across nodal metrics and a spatially heterogeneous distribution. Nodal degree was the most reliable metric and varied the least across the factors above. Hub regions in association and limbic/paralimbic cortices showed moderate TRT reliability. Importantly, nodal reliability was robust to above-mentioned four factors. Simulation analysis revealed that global network metrics were extremely sensitive (but varying degrees) to noise in functional connectivity and weighted networks generated numerically more reliable results in compared with binarized networks. For nodal network metrics, they showed high resistance to noise in functional connectivity and no NT related differences were found in the resistance. These findings provide important implications on how to choose reliable analytical schemes and network metrics of interest.
Modulating limbic-cortical circuits in depression: targets of antidepressant treatments.

Of potential importance to the development and testing of novel and more effective antidepressant therapies is the noninvasive characterization of requisite brain changes mediating depression remission. A further clinical goal is the identification of pretreatment markers that might eventually inform optimal treatment selection. Toward these objectives, functional neuroimaging studies have described resting-state glucose metabolic and blood flow abnormalities in cortical, subcortical, and limbic regions, including changes with various antidepressant treatments. There is, however, variability in both site and direction of changes across published reports. In this article, a cortical-limbic network model of depression is used to explain this variability. In this approach, network dysfunction combined with ongoing intrinsic compensatory processes is seen to explain the heterogeneity of depressive symptoms observed clinically, as well as variations in pretreatment scan patterns. Furthermore, the synchronized modulation of these dysfunctional cortical-limbic pathways is considered critical for illness remission, regardless of treatment modality. Formal testing of disease-specific and response-specific functional interactions among regions in this depression network using multivariate approaches are discussed, with a perspective aimed at future studies examining treatment nonresponse, relapse risk, and disease vulnerability.
Long-term follow-up of morbidity and mortality after aortic valve replacement with a mechanical valve prosthesis.

AIMS The aim of this study was to determine the incidence of valve-related complications in patients with a mechanical aortic valve prosthesis and to identify risk factors for an adverse outcome. METHODS AND RESULTS In the 424 patients, event-free survival rates 5 and 10 years after aortic valve replacement were 62% and 37%, respectively. The linearized incidence of thromboembolic events was 4.4% per patient-year, and of anticoagulant-related haemorrhage 8.5% per patient-year. Advanced NYHA functional class, atrial fibrillation, pure aortic regurgitation and thromboembolism prior to surgery decreased event-free survival. A history of pre-operative thromboembolism increased the risk for a first embolic event after aortic valve replacement (relative hazard [RH] 3.2), but was even more strongly associated with the risk for repeated events (> or =2 events, RH 5.4). After each thromboembolic episode that occurred, the risk for a subsequent one was increased. The risk for at least one, and up to three or more haemorrhages was increased in patients with a pre-operative history of bleeding (RH 3.3-5.1) and of atrial fibrillation (RH 1.8-3.9). The risk for a subsequent event was increased by a history of repeated haemorrhages, a short interval since previous bleeding, and high age. CONCLUSIONS There were few factors strongly related to valve related morbidity. However, previous bleedings and previous thromboembolism were powerful risk factors for repeated events.
Linguistic and Cultural Appropriations of an Immigrant Multilingual Literacy Teacher Educator

Abstract This autoethnographic self-study describes my interpretations of multicultural awareness, with special attention to multilingual awareness (MLA), based on my interactions with 52 students in the context of two literacy courses over a period of one year. An autoethnographic self-study provided an avenue to harness my reflections on practice and to study the ways in which my practice reflected awareness of my role as an educator. Findings from my teaching videos, written responses to students, and student evaluations suggested that my communication patterns with students reflected certain elements of multicultural awareness, as displayed by my attention to individual predispositions, cultural practices and personal stereotypes. The findings also appeared to indicate that multicultural and MLA interacted to reflect facilitation and symbiosis. Facilitation seemed apparent in my awareness of differences among students’ cultures and my own as I monitored my linguistic processing. Symbiosis appeared to emanate from the recognition of how my response to individual predispositions facilitated my application of conversational strategies based on feedback. This, in turn, heightened my attention to stereotypical attitudes and behaviors. Implications for multicultural teacher education include the benefits of using autoethnographic self-study to scrutinize educators’ awareness in practice as they determine the impact of this awareness on their instructional roles in multicultural teacher education. By extension, the study suggests that autoethnographic self-study research can provide additional lenses through which to interrogate monolithic perceptions of diversity in multicultural teacher education.
Myocardial Chemokine Expression and Intensity of Myocarditis in Chagas Cardiomyopathy Are Controlled by Polymorphisms in CXCL9 and CXCL10

Background Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. Methods and Results Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2–6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. Conclusions Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC.