Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Neuropsychology: Creation of Test-Specific Blood Biomarker Algorithms

Background: Prior work on the link between blood-based biomarkers and cognitive status has largely been based on dichotomous classifications rather than detailed neuropsychological functioning. The current project was designed to create serum-based biomarker algorithms that predict neuropsychological test performance. Methods: A battery of neuropsychological measures was administered. Random forest analyses were utilized to create neuropsychological test-specific biomarker risk scores in a training set that were entered into linear regression models predicting the respective test scores in the test set. Serum multiplex biomarker data were analyzed on 108 proteins from 395 participants (197 Alzheimer patients and 198 controls) from the Texas Alzheimer's Research and Care Consortium. Results: The biomarker risk scores were significant predictors (p < 0.05) of scores on all neuropsychological tests. With the exception of premorbid intellectual status (6.6%), the biomarker risk scores alone accounted for a minimum of 12.9% of the variance in neuropsychological scores. Biomarker algorithms (biomarker risk scores and demographics) accounted for substantially more variance in scores. Review of the variable importance plots indicated differential patterns of biomarker significance for each test, suggesting the possibility of domain-specific biomarker algorithms. Conclusions: Our findings provide proof of concept for a novel area of scientific discovery, which we term ‘molecular neuropsychology'.
Two types of chromosome 1p losses with opposite significance in gliomas

Deletion of the short arm of chromosome 1 (1p) is considered a favorable prognostic factor in glial tumors. High‐density array‐comparative genomic hybridization analysis of 108 gliomas shows two distinct types of 1p deletions. Complete hemizygous losses of 1p, which are tightly associated with 19q loss and oligodendroglial phenotype, and partial 1p deletions mainly observed in astrocytic tumors and not associated with 19q loss. Whereas the first type predicts longer overall and progression‐free survival (p < 0.0001), the second type has a pejorative prognostic value. Complete 1p‐arm evaluation therefore is required to appreciate the real clinical significance of 1p loss in gliomas. Ann Neurol 2005;58:483–487
EZH2 Inhibition by Tazemetostat Results in Altered Dependency on B-cell Activation Signaling in DLBCL

The EZH2 small-molecule inhibitor tazemetostat (EPZ-6438) is currently being evaluated in phase II clinical trials for the treatment of non-Hodgkin lymphoma (NHL). We have previously shown that EZH2 inhibitors display an antiproliferative effect in multiple preclinical models of NHL, and that models bearing gain-of-function mutations in EZH2 were consistently more sensitive to EZH2 inhibition than lymphomas with wild-type (WT) EZH2. Here, we demonstrate that cell lines bearing EZH2 mutations show a cytotoxic response, while cell lines with WT-EZH2 show a cytostatic response and only tumor growth inhibition without regression in a xenograft model. Previous work has demonstrated that cotreatment with tazemetostat and glucocorticoid receptor agonists lead to a synergistic antiproliferative effect in both mutant and wild-type backgrounds, which may provide clues to the mechanism of action of EZH2 inhibition in WT-EZH2 models. Multiple agents that inhibit the B-cell receptor pathway (e.g., ibrutinib) were found to have synergistic benefit when combined with tazemetostat in both mutant and WT-EZH2 backgrounds of diffuse large B-cell lymphomas (DLBCL). The relationship between B-cell activation and EZH2 inhibition is consistent with the proposed role of EZH2 in B-cell maturation. To further support this, we observe that cell lines treated with tazemetostat show an increase in the B-cell maturation regulator, PRDM1/BLIMP1, and gene signatures corresponding to more advanced stages of maturation. These findings suggest that EZH2 inhibition in both mutant and wild-type backgrounds leads to increased B-cell maturation and a greater dependence on B-cell activation signaling. Mol Cancer Ther; 16(11); 2586–97. ©2017 AACR.
A Multifaceted FISH Approach to Study Endogenous RNAs and DNAs in Native Nuclear and Cell Structures

Fluorescence in situ hybridization (FISH) is not a singular technique, but a battery of powerful and versatile tools for examining the distribution of endogenous genes and RNAs in precise context with each other and in relation to specific proteins or cell structures. This unit offers the details of highly sensitive and successful protocols that were initially developed largely in our lab and honed over a number of years. Our emphasis is on analysis of nuclear RNAs and DNA to address specific biological questions about nuclear structure, pre‐mRNA metabolism, or the role of noncoding RNAs; however, cytoplasmic RNA detection is also discussed. Multifaceted molecular cytological approaches bring precise resolution and sensitive multicolor detection to illuminate the organization and functional roles of endogenous genes and their RNAs within the native structure of fixed cells. Solutions to several common technical pitfalls are discussed, as are cautions regarding the judicious use of digital imaging and the rigors of analyzing and interpreting complex molecular cytological results. Curr. Protoc. Hum. Genet. 76:4.15. 1‐4.15. 21. © 2013 by John Wiley & Sons, Inc.
Exploring the Relationships Between Problem Gambling and ADHD: A Meta-Analysis

Objective: At present, there are inconsistencies in the literature pertaining to the association between ADHD and problem gambling. This study utilized meta-analytic techniques to clarify the association between symptoms of problem gambling and symptoms of ADHD. Method: Several meta-analyses were conducted using a random effects model. PsycINFO, PubMed, ProQuest Dissertations & Theses, and Google Scholar were searched for relevant studies. Results: The weighted mean correlation between ADHD symptomology and gambling severity was r = . 17, 95% confidence interval (CI) = [0.12, 0.22], p < . 001. Mean age of the sample was the only moderator to approach significance, with greater age being linked to a stronger relationship between symptoms of ADHD and gambling severity. Conclusion: Clinicians needs to be cognizant of the greater risk of ADHD symptoms when working with problem gamblers and vice versa.
th International Conference Interdisciplinarity in Engineering , INTER-ENG 2015 , 8-9 October 2015 , Tirgu-Mures , Romania Biometric authentication based on touchscreen swipe patterns

In this work we investigated user authentication on mobile devices using touch behavior and micro movements of the device. The novelty of our work lies in the collection of user behavior data during the filling in of a psychological questionnaire (implemented as an Android application). In order to answer the questions, users were required to use a slider. Therefore users were constrained to using only straight horizontal swipes. Extensive evaluations were conducted on the resulting dataset using oneand two-class classification algorithms. Although authentication EER based on single swipe is around 4%, this was improved by using sequences of 5 swipes (0.2% EER). Features related to micro movement of the device proved to be the most discriminating ones. c © 2016 The Authors. Published by Elsevier Ltd. Published by Elsevier Ltd. Peer-review under responsibility of the “Petru Maior” University of Tirgu-Mures, Faculty of Engineering.
Identification of Potential Tyrosine-containing Endocytic Motifs in the Carboxyl-tail and Seventh Transmembrane Domain of the Neurokinin 1 Receptor*

Although agonist-induced endocytosis of G-protein-coupled receptors is critical for receptor desensitization and resensitization, receptor motifs that interact with the endocytic apparatus have not been adequately characterized. We examined the effects of mutating the rat neurokinin-1 receptor on endocytosis using 125I-substance P, fluorescent substance P, and receptor antibodies. Substance P induced rapid internalization of wild-type receptors that were targeted to perinuclear endosomes. Truncation of the C-tail at residues 324, 342, and 354 reduced internalization up to 60% and caused retention of receptors at the cell surface and in superficial endosomes. Mutation of Tyr-341 and Tyr-349 in potential tyrosine-containing endocytic motifs of the C-tail also impaired internalization. A Y305A mutant within the putative NPX2-3Y endocytic motif of the seventh transmembrane domain showed impaired signaling and was minimally expressed at the plasma membrane but was found in cytoplasmic vesicles. In contrast, a Y305F mutant signaled normally and was normally expressed at the plasma membrane but showed impaired internalization. Thus, endocytosis of the neurokinin 1 receptor relies on several tyrosine-containing sequences in the C-tail and seventh transmembrane domain.
ACID‐BASE IN RENAL FAILURE: Acidosis and Nutritional Status in Hemodialyzed Patients

In a cross‐sectional study of more than 30% of French dialysis patients (N = 7,123), we evaluated the relationships between predialysis plasma bicarbonate concentration and nutritional markers. Data including age, gender, cause of end‐stage renal disease (ESRD), time on dialysis, body mass index (BMI), blood levels of midweek predialysis albumin, prealbumin, and bicarbonate were collected. Normalized protein catabolic rate (nPCR), dialysis adequacy parameters, and estimation of lean body mass (LBM) were computed from pre‐ and postbicarbonate‐dialysis urea and creatinine levels according to the classical formulas of Garred. Average values (±1 SD) were age 61 ± 16 years, BMI 23.3 ± 4.6 kg/m2, dialysis time 12.4 ± 2.7 h/week, HCO3 22.8 ± 3.5 mmol/L, albumin 38.7 ± 5.3 g/L, prealbumin 340 ± 90 mg/L, Kt/V 1.36 ± 0.36, nPCR 1.13 ± 0.32 g/kg BW/day, and LBM 0.86 ± 0.21% of ideal LBM. A highly significant negative correlation was observed between predialysis bicarbonate levels (within a range of 16–30 mmol/L, 95% of this population) and nPCR confirmed by analysis of variance using bicarbonate classes (p < 0.0001). Bicarbonate was also negatively correlated with albumin, prealbumin, BMI, and LBM. No relationship was noted between bicarbonate and Kt/V despite a positive correlation between Kt/V and nPCR. It is likely that a persistent acidosis observed despite standard bicarbonate dialysis was caused by a high dietary protein intake which results in an increased acid load, but also overcomes the usual catabolic effects of acidosis.
The Prolog Interface to the Unstructured Information Management Architecture

In this paper we describe the design and implementation of the Prolog interface to the Unstructured Information Management Architecture (UIMA) and some of its applications in natural language processing. The UIMA Prolog interface translates unstructured data and the UIMA Common Analysis Structure (CAS) into a Prolog knowledge base, over which, the developers write rules and use resolution theorem proving to search and generate new annotations over the unstructured data. These rules can explore all the previous UIMA annotations (such as, the syntactic structure, parsing statistics) and external Prolog knowledge bases (such as, Prolog WordNet and Extended WordNet) to implement a variety of tasks for the natural language analysis. We also describe applications of this logic programming interface in question analysis (such as, focus detection, answer-type and other constraints detection), shallow parsing (such as, relations in the syntactic structure), and answer selection.
The Effectiveness of Revenue Generation in the Evaluation System of the Tax Burden on Personal Income: Application of Stochastic Frontier Analysis Considers the Dynamics of Regional Data

Taxes play an important role in development of separate territories of the country. At the same time the size of taxes collected depends on the size of income received. Taking into consideration this fact this paper describes income of the population as a component of system analyses of household income taxation burden. In particular the assessment of efficiency of incomes received by the population for each region taking separately in line. In order to consider the efficiency of incomes received by the population the method of stochastic frontier analyses in dynamics is used. The functional parameters of the frontier model of population’s income generation efficiency broken down by the time aspects are estimated. The answers about interrelation between changes in taxable income tax burden and changes in the corresponding estimates of population’s income generation efficiency broken down by their regional aspects are given. The proposal about the need for the growth in average salary from the point of view of population’s income generation and consequently from the point of view of the growth of efficiency in corresponding taxes fiscal performance are given.
LeeTL: LTL with quantifications over model objects

Dynamic creating of objects and processes as one of the widely used techniques for developing models does not support by the majority of model checking tools. In addition, although there exist few model checking tools which support dynamic creation of model elements, e.g. Spin, they do not provide a property language for presenting the behavioral specifications of dynamically created elements. In this paper, we address this shortage and provide proper support for the model checking of object-based models which contain dynamic object creation. To this aim, we propose LeeTL, a new temporal logic that supports quantifications over model objects. Using LeeTL, it is also possible to traverse objects to access the variables of the objects for defining property formulas. We propose an algorithm for transforming LeeTL formulas to Büchi automata to be able to use the existing model checking tools which support Büchi automata.
QapR (PA5506) Represses an Operon That Negatively Affects the Pseudomonas Quinolone Signal in Pseudomonas aeruginosa

ABSTRACT Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that can cause disease in varied sites within the human body and is a significant source of morbidity and mortality in those afflicted with cystic fibrosis. P. aeruginosa is able to coordinate group behaviors, such as virulence factor production, through the process of cell-to-cell signaling. There are three intercellular signaling systems employed by P. aeruginosa, and one of these systems utilizes the small molecule 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas quinolone signal [PQS]). PQS is required for virulence in multiple infection models and has been found in the lungs of cystic fibrosis patients colonized by P. aeruginosa. In this study, we have identified an RpiR family transcriptional regulator, QapR, which is an autoregulatory repressor. We found that mutation of qapR caused overexpression of the qapR operon. We characterized the qapR operon to show that it contains genes qapR, PA5507, PA5508, and PA5509 and that QapR directly controls the transcription of these genes in a negative manner. We also show that derepression of this operon greatly reduces PQS concentration in P. aeruginosa. Our results suggest that qapR affects PQS concentration by repressing an enzymatic pathway that acts on PQS or a PQS precursor to lower the PQS concentration. We believe that this operon comprises a novel mechanism to regulate PQS concentration in P. aeruginosa.
Learning Rounds: what the literature tells us (and what it doesn’t)

Learning Rounds is a form of professional development that has gained widespread currency in Scotland. It has received official endorsement from Scottish Government funded agencies and has spread as a practice through at least 24 out of 32 local authorities, in part through popular adoption by teachers. However the literature on Instructional Rounds that informs Learning Rounds is not as well known in Scotland as the practice of Learning Rounds itself. An earlier small scale study of Learning Rounds in Scotland suggests that practice varies significantly from school to school and from the original practices of Instructional Rounds. This literature review provides a critical survey of the existing literature on Instructional Rounds and Learning Rounds. This is intended to enable educators to be more informed about whether to adopt the practice and how to develop and evaluate the practice if they do.
Pneumocystis jiroveci Dihydropteroate Synthase Polymorphisms Confer Resistance to Sulfadoxine and Sulfanilamide in Saccharomyces cerevisiae

ABSTRACT Failure of anti-Pneumocystis jiroveci prophylaxis with sulfa drugs is associated with mutations within the putative active site of the fungal dihydropteroate synthase (DHPS), an enzyme encoded by the multidomain FAS gene. This enzyme is involved in the essential biosynthesis of folic acid. The most frequent polymorphisms are two mutations leading to two amino acid changes (55Trp-Arg-57Pro to 55Ala-Arg-57Ser), observed as a single or double mutation in the same P. jiroveci isolate. In the absence of a culture method for P. jiroveci, we studied potential resistance to sulfa drugs conferred by these polymorphisms by using Saccharomyces cerevisiae as a model. Single or double mutations identical to those observed in the DHPS domain of the P. jiroveci FAS gene were introduced by in vitro site-directed mutagenesis into alleles of the S. cerevisiae FOL1 gene, which is the orthologue of the P. jiroveci FAS gene. The mutated alleles were integrated at the genomic locus in S. cerevisiae and expressed by functional complementation in a strain with a disrupted FOL1 allele. The single mutation 55Trp to 55Ala conferred resistance to sulfanilamide, whereas the single mutation 57Pro to 57Ser conferred resistance to both sulfanilamide and sulfadoxine. Both single mutations also separately conferred hypersensitivity to sulfamethoxazole and dapsone. The resistance to sulfadoxine is consistent with epidemiological data on P. jiroveci. The double mutation 55Trp-Arg-57Pro to 55Ala-Arg-57Ser conferred on S. cerevisiae a requirement for p-aminobenzoate, suggesting reduced affinity of DHPS for this substrate. This characteristic is commonly observed in mutated DHPS enzymes conferring sulfa drug resistance from other organisms. However, the double mutation conferred hypersensitivity to sulfamethoxazole, which is not in agreement with epidemiological data on P. jiroveci. Taken together, our results suggest that the DHPS polymorphisms observed in P. jiroveci confer sulfa drug resistance on this pathogen.
Strong association between capsular type and virulence for mice among human isolates of Streptococcus pneumoniae

The relationship between capsular type and virulence for mice was examined with 69 fresh human isolates of Streptococcus pneumoniae. These isolates represented eight capsular types or groups. Serologic and molecular weight differences in PspA (pneumococcal surface protein A) indicated that the strains were clonally distinct. Mice were infected intravenously with washed bacteria of all 69 isolates in sterile salt solutions. Twenty-eight of the isolates were also injected intraperitoneally to permit comparisons between the intravenous and intraperitoneal routes. With a few exceptions, there was concordance between the ability of strains to cause fatal infections by the two routes. About 30% of the 69 isolates were virulent for mice. The abilities of the isolates to kill mice and the length of time between inoculation and death were strongly associated with capsular type. All type 4 isolates, 40% of type 3 isolates, and 60% of group 6 isolates were virulent for mice; type 1 isolates were marginally virulent; and all type or group 14, 19, and 23 isolates were avirulent. Times to death were generally longer for mice infected with group 6 or type 1 than for those infected with type 3 or 4 pneumococci. There was no relationship between clinical diagnosis or tissue source of the isolates and virulence for mice.
Spontaneous and 5-azacytidine-induced reexpression of ornithine carbamoyl transferase in hepatoma cells

Rat hepatoma cells that do not synthesize the hepatic enzyme ornithine carbamoyl transferase spontaneously give rise to producing cells at a low frequency. Reexpression of this differentiation trait is strongly increased by 5-azacytidine treatment, suggesting that hypermethylation plays a critical role in the impaired expression of the ornithine carbamoyl transferase gene in hepatoma cells.
Separate pools of endonuclease activity are responsible for internucleosomal and high molecular mass DNA fragmentation during apoptosis.

The oligonucleosomal pattern of DNA fragmentation is the best-characterized biochemical marker of apoptosis and believed to be generated by a, as yet unidentified, Ca2+, Mg(2+)-dependent endonuclease. All apoptotic cells fragment their genome. However, not every cell type undergoing apoptosis is capable of internucleosomal DNA cleavage. We have analyzed the endonuclease activities and patterns of DNA fragmentation in four established cell lines undergoing apoptosis following serum deprivation, i.e., rat 5123tc hepatoma and PC12 pheochromocytoma, as well as human MCF7 breast and DU145 prostatic carcinoma cells. Whereas apoptotic 5123tc and PC12 cells degraded their DNA into oligonucleosomes, the MCF7 and DU145 cells generated only > 50 kilobase pairs (kbp) DNA fragments. However, when isolated nuclei from all four cell lines were incubated with both Ca2+ and Mg2+ ions, their DNA was cleaved into internucleosomal fragments. Following washing with a low ionic strength buffer, the nuclei could only degrade DNA to > 50-kbp fragments. DNA ladders were produced again in these washed nuclei after reconstitution with the nuclear wash, which contained an endonucleolytic activity of approximately 97 kilodaltons. These experiments showed that cells maintain separate pools of endonucleolytic activities responsible for the high and low molecular mass DNA fragmentation, and depending on the cell type, one or both enzymatic pools become activated during apoptosis.
Quantum ballistic transport in ultra-small silicon channel cylindrical gate-all-around junction less nanowire transistor using NEGF formalism

This work investigates quantum ballistic transport in ultra-small junctionless semiconducting nanowire transistors, within the framework of self-consistent Schrodinger-Poisson problem. A sub-band decomposition approach has been taken to make the problem numerically tractable. Finally simulated transport characteristics for small diameter (d≤5 nm) n-Si-channel cylindrical gate-all-around junctionless nanowire transistor are discussed. The DIBL and SS of this novel device is compared with cylindrical gate-all-around nanowire MOSFET and rectangular gate-all-around junctionless nanowire transistor data. The results show a much better prospect of scaling down with cylindrical gate junctionless nanowire transistor, which may be advantageous for use in integrated circuit industry.