Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of the Candida albicans Hypha-Inducing Transcription Factor Ume6 by the CDK1 Cyclins Cln3 and Hgc1

The yeast to hypha (mold) morphogenetic switch of Candida albicans plays a role in its virulence and constitutes a diagnostic trait for this organism, the most prevalent systemic fungal pathogen in industrialized countries. It has long been known that hyphae are most efficiently induced from stationary cultures. Here, a molecular basis for this observation is provided. The G1 cyclin Cln3, an essential promoter of yeast proliferation, was found to suppress hyphal induction. Suppression of hyphal induction is achieved by inhibition of the activity of the central activator of hyphal morphogenesis, the transcription factor Ume6. Thus, levels of Cln3 control the switch between proliferation of C. albicans as individual yeast cells and development into extended hyphae, a switch that may preface the proliferation/differentiation switch in multicellular organisms. ABSTRACT The ability to switch between proliferation as yeast cells and development into hyphae is a hallmark of Candida albicans. The switch to hyphal morphogenesis depends on external inducing conditions, but its efficiency is augmented in stationary-phase cells. Ume6, a transcription factor that is itself transcriptionally induced under hypha-promoting conditions, is both necessary and sufficient for hyphal morphogenesis. We found that Ume6 is regulated posttranslationally by the cell cycle kinase Cdc28/Cdk1, which reduces Ume6 activity via different mechanisms using different cyclins. Together with the cyclin Hgc1, Cdk1 promotes degradation of Ume6 via the SCFCDC4 ubiquitin ligase. Since HGC1 is a key transcriptional target of Ume6, this results in a negative-feedback loop between Hgc1 and Ume6. In addition, we found that Cln3, a G1 cyclin that is essential for cell cycle progression and yeast proliferation, suppresses hyphal morphogenesis and that Cln3 suppresses Ume6 activity both in the heterologous Saccharomyces cerevisiae system and in C. albicans itself. This activity of Cln3 may provide the basis for the antagonistic relationship between yeast proliferation and hyphal development in C. albicans. IMPORTANCE The yeast to hypha (mold) morphogenetic switch of Candida albicans plays a role in its virulence and constitutes a diagnostic trait for this organism, the most prevalent systemic fungal pathogen in industrialized countries. It has long been known that hyphae are most efficiently induced from stationary cultures. Here, a molecular basis for this observation is provided. The G1 cyclin Cln3, an essential promoter of yeast proliferation, was found to suppress hyphal induction. Suppression of hyphal induction is achieved by inhibition of the activity of the central activator of hyphal morphogenesis, the transcription factor Ume6. Thus, levels of Cln3 control the switch between proliferation of C. albicans as individual yeast cells and development into extended hyphae, a switch that may preface the proliferation/differentiation switch in multicellular organisms.
Discovering Closely Related Peers of a Person in Social Networks

In social networks, finding a group of similar people of a specified person is meaningful task in many areas like substitution/alternate recommendation system. For a given person, considering hobbies, interests etc., as base forming a group of peers from social networks. Here we propose mutual unique identification group(MUID) algorithm for identifying closely related peers.
Evidências de Validade da Escala de Flexibilidade Psicológica no Trabalho em Amostras Brasileiras

The psychological flexibility at work is related to the ability of the individuals to take work goal directed actions, even in the presence of difficult internal experiences. The study aimed to adapt and gather evidences of validity of the Scale of Psychological Flexibility at Work (WAAQ) in the Brazilian context. The sample consisted of 583 employees, of both sexes, aged 18-62 years. Confirmatory factor analyzes showed that the Brazilian version of the scale reproduced fully the original structure of the instrument. The scale has also presented positive correlations with job engagement, mental health, openness to experience and life satisfaction, as well as a negative correlation with neuroticism. It was concluded that the WAAQ showed adequate psychometric properties and can therefore be used in the future research of flexibility at the workplace.
Selective Ion Changes during Spontaneous Mitochondrial Transients in Intact Astrocytes

The bioenergetic status of cells is tightly regulated by the activity of cytosolic enzymes and mitochondrial ATP production. To adapt their metabolism to cellular energy needs, mitochondria have been shown to exhibit changes in their ionic composition as the result of changes in cytosolic ion concentrations. Individual mitochondria also exhibit spontaneous changes in their electrical potential without altering those of neighboring mitochondria. We recently reported that individual mitochondria of intact astrocytes exhibit spontaneous transient increases in their Na+ concentration. Here, we investigated whether the concentration of other ionic species were involved during mitochondrial transients. By combining fluorescence imaging methods, we performed a multiparameter study of spontaneous mitochondrial transients in intact resting astrocytes. We show that mitochondria exhibit coincident changes in their Na+ concentration, electrical potential, matrix pH and mitochondrial reactive oxygen species production during a mitochondrial transient without involving detectable changes in their Ca2+ concentration. Using widefield and total internal reflection fluorescence imaging, we found evidence for localized transient decreases in the free Mg2+ concentration accompanying mitochondrial Na+ spikes that could indicate an associated local and transient enrichment in the ATP concentration. Therefore, we propose a sequential model for mitochondrial transients involving a localized ATP microdomain that triggers a Na+-mediated mitochondrial depolarization, transiently enhancing the activity of the mitochondrial respiratory chain. Our work provides a model describing ionic changes that could support a bidirectional cytosol-to-mitochondria ionic communication.
Stereotactic Microanatomy of the Nucleus Accumbens Stimulation for Obsessive-Compulsive Disorder: Reported Coordinates and Mavridis' Area.

decades of endonasal surgery for the senior authors and represents the practical distillation of this experience to provide real-time, meaningful surgical landmarks. Every segment described in this article has been accessed effectively through the use of the representative landmark in an actual patient during surgery. Thus, this work is presented to others to replicate these approaches without having to redefine these landmarks.
A Framework for Polarity Classification and Emotion Mining from Text

No wadays Online Social Networks are so popular that they are become a major component of an individual's social interaction. They are also emotionally-rich environ ments where users share their emotions, feelings, ideas and thoughts. In this paper, a novel framework is proposed for characterizing emotional interactions in social networks. The aim is to extract the emotional content of texts in online social networks. The interest is in to determine whether the text is an exp ression of the writer's emotions or not if yes then what type of emotion likes happy, sad, angry, disgust, fear, surprise. For this purpose, text mining techniques are performed on comments/messages from a social network. The framework provides a model for d ata collection, feature generation, data preprocessing and data min ing steps. In general, the paper presents a new perspective fo r studying emotions' expression in online social networks. The technique adopted is unsupervised; it main ly uses the k-means clustering algorithm and nearest neighbor algorithm. Experiments show high accuracy for the model in both determin ing subjectivity of texts and predicting e motions.
Coronary microvascular reserve and outcome in aortic stenosis: Pathophysiological significance vs. clinical relevance

This editorial refers to ‘Comparison of exercise testing and cardiovascular magnetic resonance-measured myocardial perfusion reserve for predicting outcome in asymptomatic aortic stenosis: the PRognostic Importance of MIcrovascular Dysfunction in Aortic Stenosis (PRIMID AS) study’, by A. Singh et al. doi:10.1093/eurheartj/ehx001. Degenerative aortic stenosis (AS) is one of the most common valvular diseases in developed countries.1 AS is a progressive disease for which the only effective treatment is surgical or transcatheter aortic valve replacement (AVR). 2,3 Patients with mild to moderate AS require no specific valve treatment, whereas AVR is indicated in patients with severe symptomatic AS. The main conundrum in the management of AS relates to the timing of AVR in almost half of the patients who have severe AS but do not report clinical symptoms at the time of diagnosis.4 This uncertainty is mainly fed by the fact that no study has so far compared prospectively the outcomes in asymptomatic patients with severe AS undergoing watchful waiting and those undergoing AVR. Analysing all the previous studies reporting all-cause mortality in patients with asymptomatic AS who underwent AVR and those managed conservatively pointed to significant bias and data heterogeneity, preventing any valid conclusion.5 Delaying AVR in severe AS until symptoms appear represents for most clinicians the fear that patients may present with irreversible myocardial damage, sudden cardiac death, or a rapidly progressive disease, especially in the absence of appropriate monitoring.6 Hence, there is a crucial need to enable a prospective detection of patients with AS who will benefit from AVR before they become symptomatic. Based on the pathophysiological events occurring during valvular and myocardial remodelling in AS, several clinical, biological, and imaging parameters are currently being considered at different levels of evidence to help decision-making in asymptomatic severe AS.7 Coronary microvascular dysfunction …
Dynamics of Recovery of Functions of the Nasal Cavity in Patients with Aspirin-Intolerant Polypous Rhinosinusitis in the Postoperative Period

Surgical interventions in the nasal cavity are accompanied by reactive phenomena in the postoperative period. On their background the process of physiological regeneration is disorganized resulting in impaired physiological functions of the nasal cavity. The objective of the research was to study the recovery process of the main physiological functions of the nasal cavity in patients with aspirin-intolerant polypous rhinosinusitis in the postoperative period. Materials and methods. 80 patients with aspirin-intolerant polypous rhinosinusitis at the age of 24-57 years were operated on.All the patients were divided into 2 groups: the control group included 30 patients; the main group comprised 50 patients.Patients of the control group received nasal cavity cleaning, nasal mucosa anemisation, irrigation therapy since the first day of the postoperative period.Patients of the main group received an herbal drug BNO-101 additionally. The effectiveness was assessed on the 3 rd , 7 th and 10 th days of treatment. Results. The postoperative rehabilitation with the inclusion of botanical preparation BNO-101 provided a significant improvement of nasal breathing, mucociliary transport rate and indicators of nasal peak flowmetry compared to the control group. Despite subjective improvement of nasal breathing the indicators of the peak expiratory flow rate in the main group were 34.2% lower than the norm while in the control group they were 54.7% lower than normal ones thereby justifying further treatment. Conclusions. The postoperative rehabilitation of patients with aspirin-intolerant polypous rhinosinusitis provided more rapid improvement of the main functions of the nasal cavity compared to the control group.
Primary Liver Cancers, Part 2

Hepatocellular carcinoma (HCC) and primary intrahepatic cholangiocarcinoma (ICC) have been increasing in incidence worldwide and are leading causes of cancer death. Studies of the molecular alterations leading to these carcinomas provide insights into the key mechanisms involved. A literature review was conducted to identify articles with information relevant to current understanding of the etiologies and molecular pathogenesis of HCC and ICC. Chronic inflammatory diseases are the key etiological risk factors for both HCC and ICC, although other diseases play a role, and for many ICCs, an underlying risk factor is not identified. Mutations in catenin beta 1 (CTNBB1) and tumor protein 53 (P53) are the main genetic alterations in HCC. Isocitrate dehydrogenases 1 and 2 (IDH1/2), KRAS protooncogene GTPase (KRAS), a RAS Viral Oncogene Homolog in neoroblastoma (NRAS) and P53 are primary genetic alterations in ICC. In both diseases, the mutational landscape is dependent on the underlying etiology. The most significant etiologies and genetic processes involved in the carcinogenesis of HCC and ICC are reviewed.
Serum lipids associated with inflammation-related PET-FDG uptake in symptomatic carotid plaque

Objective: We hypothesized that serum lipids, which experimental data suggest may be key initiators of carotid plaque inflammation, would be associated with plaque inflammation on 18fluorodeoxyglucose (FDG)-PET in patients with acutely symptomatic carotid stenosis. Methods: In this cohort study, consecutive patients with acute symptomatic internal carotid artery (ICA) stenosis (≥50%) underwent carotid PET-CT. We quantified plaque FDG uptake as follows: (1) average maximum standardized uptake values (SUVmax) across 10 regions of interest (ROI); (2) highest single ROI SUV measure (SUVROImax); (3) averaged mean SUV across 10 ROIs (SUVmean). Results: Sixty-one patients were included. Plaque inflammatory FDG SUVmax was associated with increasing tertiles of low-density lipoprotein (LDL) (trend p = 0.004), total cholesterol (p = 0.009), and triglycerides (p = 0.01), and with lower high-density lipoprotein (HDL) (p = 0.005). When analyzed as a continuous variable, LDL was associated with symptomatic ICA SUVmean (Spearman rho 0.44, p = 0.009), SUVROImax (rho 0.33, p = 0.01), and SUVmax (rho 0.35, p = 0.06). Total cholesterol was associated with SUVmean (rho 0.33, p = 0.009), with trends for SUVmax (rho 0.24, p = 0.059) and SUVROImax (rho 0.23, p = 0.08). Triglycerides were associated with SUVmax (rho 0.32, p = 0.01) and SUVROImax (rho 0.35, p = 0.005). HDL was associated with lower SUVmax (rho −0.37, p = 0.004) and SUVROImax (rho −0.44, p = 0.0004). On multivariable linear regression analysis adjusting for age, sex, degree of carotid stenosis, statins, and smoking, LDL (p = 0.008) and total cholesterol (p = 0.04) were independently associated with SUVmax. Conclusion: Serum LDL and total cholesterol were associated with acutely symptomatic carotid plaque FDG uptake, supporting experimental data suggesting lipids may promote plaque inflammation, mediating rupture and clinical events.
Compressed orally disintegrating tablets: excipients evolution and formulation strategies

Introduction: Orally disintegrating tablets (ODTs) have emerged as one of the novel solid oral dosage forms with a potential to deliver a wide range of drug candidates to both paediatric and geriatric patient populations. Of the plethora of available technologies, compression of excipients offers a cost-effective and translatable methodology for the manufacture of ODTs. Areas covered: The review is a modest endeavour from the authors to assemble literature published over the last couple of decades on formulation development of compressed ODT. It describes the main ODT excipients used since the introduction of this dosage form in the 1990s and explores the switch from cellulose-based excipients towards sugar/polyols. Furthermore, it unfolds the key properties of ODT fillers, binders and disintegrants with an emphasis on their advantages and drawbacks. The review also provides a critical assessment of the various strategies employed for performance enhancement of compressed ODT with a focus on the underlying mechanisms for fast disintegration and acceptable mechanical strength. Expert opinion: Recent increase in the total number of compression-based technologies for ODT development promises to reduce the manufacturing cost of this dosage form in the future. However, some of the developed methods may affect the stability of tablets due to susceptibility to moisture, collapse of pores or the generation of less stable polymorphs which require rigorous testing prior to commercialization.
If Nobody is Going There Anymore Because it's Too Crowded, Then Who is Going? Experimental Evidence of Learning And Imitation in the El Farol Coordination Game

This paper is a study of Yogi Berra's colorful non sequitur: "Nobody goes there anymore. It's too crowded. " Many economic markets remind one of Berra's insightful observation. One desires to buy an asset, such as a stock, when more people are selling than buying. However, this situation increases the number of buyers and tips the market to favor sellers. This paper evaluates coordination among agents in these environments. In particular, this paper discusses how people implicitly learn to coordinate their actions when such coordination is beneficial, but difficult. It uses the experimental method pioneered by Nobel Laureate Vernon Smith. During a series of experiments involving human subjects and simulated agents, subjects repeatedly update their strategies during play of a coordination game known as the El Farol Bar Game. In this experiment a subject is able to partially observe her opponents' previous strategies and payoffs before setting her strategy for the next round of play. Results indicate that play did not converge to the stage game's pure strategy Nash equilibrium. Also, subjects routinely imitated the most successful strategies. This flocking behavior led to socially inefficient outcomes.
Analysis of p-type Junctionless nanowire transistors with different crystallographic orientations

This work presents an analysis of the influence of the crystal orientation on the performance of p-type Junctionless Nanowire Transistors. The main electrical parameters, such as threshold voltage, transconductance and subthreshold slope, were analyzed by means of experimental data, demonstrating that the substrate rotation can significantly worsen the electrical behavior of these devices.
Inference for the Lognormal Mean and Quantiles Based on Samples With Left and Right Type I Censoring

Interval estimation of the mean and quantiles of a lognormal distribution is addressed based on a Type I singly censored sample. A special case of interest is that of a sample containing values below a single detection limit. Generalized inferential procedures which use maximum likelihood estimation based approximate pivotal quantities, and some likelihood based methods, are proposed. The latter include methodology based on the signed log-likelihood ratio test (SLRT) statistic and the modified signed log-likelihood ratio test (MSLRT) statistic. The merits of the methods are evaluated for a left-censored sample using Monte Carlo simulation. For inference concerning the lognormal mean, the SLRT is to be preferred for left-tailed testing, generalized inference for right-tailed testing, and all three approaches provide nearly the same performance for two-tailed testing. These conclusions hold even when the proportion of censored values is as large as 0.70. For inference concerning quantiles, both the generalized inference approach and the MSLRT approach are satisfactory. In view of its simplicity and ease of understanding and implementation, the generalized inference procedure is to be preferred. The results are illustrated with two examples. Technical derivations are given on the Technometrics website as supplementary material.
First-sphere and second-sphere electrostatic effects in the active site of a class mu gluthathione transferase.

The activation of the thiol of glutathione (GSH) bound in the active site of the class mu glutathione transferase M1-1 from rat involves a hydrogen-bonding network that includes a direct (first-sphere) interaction between the hydroxyl group of Y6 and the sulfur of GSH and second-sphere interactions involving a hydrogen bond between the main-chain amide N-H of L12 and the hydroxyl group of Y6 and an on-face hydrogen bond between the hydroxyl group of T13 and the pi-electron cloud of Y6 (i.e., T13-OH---pi-Y6-OH--- -SG). The functions of these hydrogen bonds have been examined with a combination of site-specific mutagenesis and X-ray crystallography. The hydroxyl group of Y6 has a normal pKa of about 10 even though it is shielded from solvent and is in a largely hydrophobic environment. The apparent pKa of GSH in the binary Y6F.GSH complex is increased by 1.6 log units, and the reactivity of the enzyme-bound nucleophile is reduced. The catalytic properties of the Y6L mutant are identical to those of Y6F, suggesting that the weakly polar on-edge interaction between the aromatic ring and sulfur has no influence on catalysis. The refined three-dimensional structure of the Y6F mutant in complex with GSH shows no major structural perturbation of the protein other than a change in the coordination environment of the sulfur. Removal of the second-sphere influence of the on-face hydrogen bond between the hydroxyl groups T13 as in the T13V and T13A mutants elevates the pKa of enzyme-bound GSH by about 0.7 pKa units. Crystal structures of these mutants show that structural changes in the active site are minor and suggest that the changes in pKa of E.GSH are due to the presence or absence of the on-face hydrogen bond. The T13S mutant has a completely different side-chain hydrogen-bonding geometry than T13 in the native enzyme and catalytic properties similar to the T13A and T13V mutants consistent with the absence of an on-face hydrogen bond. The gamma-methyl group of T13 is essential in enforcing the on-face hydrogen bond geometry and preventing the hydroxyl group from forming more favorable conventional hydrogen bonds.
Shifting Attitudes: The Influence of Field Trip Experiences on Student Beliefs

This paper reports on the findings of a review of the literature on interactions between affective and cognitive learning, in general, and, specifically, during field trips for university students in natural science or engineering disciplines. The paper presents a study that tests concepts raised from the literature review by exploring affective learning during a 10-day field trip to a water-poor region of Mexico. Student beliefs about the relevance of water resource management are compared before and after the field trip using a survey instrument. Also, student beliefs are compared to those of water resource experts. Results of the study are put in the context of the literature and strategies are recommended for optimizing affective learning within experiential, informal activities such as field trips.