Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel mutation L260P of the steroidogenic acute regulatory protein gene in three unrelated patients of Swiss ancestry with congenital lipoid adrenal hyperplasia.

CONTEXT Lipoid congenital adrenal hyperplasia (CAH) is the most severe form of CAH leading to impaired production of all adrenal and gonadal steroids. Mutations in the gene encoding steroidogenic acute regulatory protein (StAR) cause lipoid CAH. OBJECTIVE We investigated three unrelated patients of Swiss ancestry who all carried novel mutations in the StAR gene. All three subjects were phenotypic females with absent Müllerian derivatives, 46,XY karyotype, and presented with adrenal failure. METHODS AND RESULTS StAR gene analysis showed that one patient was homozygous and the other two were heterozygous for the novel missense mutation L260P. Of the heterozygote patients, one carried the novel missense mutation L157P and one had a novel frameshift mutation (629-630delCT) on the second allele. The functional ability of all three StAR mutations to promote pregnenolone production was severely attenuated in COS-1 cells transfected with the cholesterol side-chain cleavage system and mutant vs. wild-type StAR expression vectors. CONCLUSIONS These cases highlight the importance of StAR-dependent steroidogenesis during fetal development and early infancy; expand the geographic distribution of this condition; and finally establish a new, prevalent StAR mutation (L260P) for the Swiss population.
A Chebyshev criterion for Abelian integrals

We present a criterion that provides an easy sufficient condition in order for a collection of Abelian integrals to have the Chebyshev property. This condition involves the functions in the integrand of the Abelian integrals and can be checked, in many cases, in a purely algebraic way. By using this criterion, several known results are obtained in a shorter way and some new results, which could not be tackled by the known standard methods, can also be deduced.
Forensic Human Identification Using Skin Microbiomes

ABSTRACT The human microbiome contributes significantly to the genetic content of the human body. Genetic and environmental factors help shape the microbiome, and as such, the microbiome can be unique to an individual. Previous studies have demonstrated the potential to use microbiome profiling for forensic applications; however, a method has yet to identify stable features of skin microbiomes that produce high classification accuracies for samples collected over reasonably long time intervals. A novel approach is described here to classify skin microbiomes to their donors by comparing two feature types: Propionibacterium acnes pangenome presence/absence features and nucleotide diversities of stable clade-specific markers. Supervised learning was used to attribute skin microbiomes from 14 skin body sites from 12 healthy individuals sampled at three time points over a >2.5-year period with accuracies of up to 100% for three body sites. Feature selection identified a reduced subset of markers from each body site that are highly individualizing, identifying 187 markers from 12 clades. Classification accuracies were compared in a formal model testing framework, and the results of this analysis indicate that learners trained on nucleotide diversity perform significantly better than those trained on presence/absence encodings. This study used supervised learning to identify individuals with high accuracy and associated stable features from skin microbiomes over a period of up to almost 3 years. These selected features provide a preliminary marker panel for future development of a robust and reproducible method for skin microbiome profiling for forensic human identification. IMPORTANCE A novel approach is described to attribute skin microbiomes, collected over a period of >2.5 years, to their individual hosts with a high degree of accuracy. Nucleotide diversities of stable clade-specific markers with supervised learning were used to classify skin microbiomes from a particular individual with up to 100% classification accuracy for three body sites. Attribute selection was used to identify 187 genetic markers from 12 clades which provide the greatest differentiation of individual skin microbiomes from 14 skin sites. This study performs skin microbiome profiling from a supervised learning approach and obtains high classification accuracy for samples collected from individuals over a relatively long time period for potential application to forensic human identification.
Problems with tense marking in children with specific language impairment: not how but when

Many children with specific language impairment (SLI) have persisting problems in the correct use of verb tense, but there has been disagreement as to the underlying reason. When we take into account studies using receptive as well as expressive language tasks, the data suggest that the difficulty for children with SLI is in knowing when to inflect verbs for tense, rather than how to do so. This is perhaps not surprising when we consider that tense does not have a transparent semantic interpretation, but depends on complex relationships between inflections and hierarchically organized clauses. An explanation in terms of syntactic limitations contrasts with a popular morpho-phonological account, the Words and Rules model. This model, which attributes problems to difficulties with applying a rule to generate regular inflected forms, has been widely applied to adult-acquired disorders. There are striking similarities in the pattern of errors in adults with anterior aphasia and children with SLI, suggesting that impairments in appreciation of when to mark tense may apply to acquired as well as developmental disorders.
ACTIVITY OF HOST-DERIVED T CELLS WHICH DIFFERENTIATE IN NUDE MICE GRAFTED WITH CO-ISOGENIC OR ALLOGENEIC THYMUSES

If nude mice are grafted with a neonatal thymus, host type precursor cells develop within the graft thymus and after about 6 wk the T-cell population of the thymus, spleen, and lymph nodes is of host type. However, immunological responsiveness produced in nude mice in this manner is incomplete: (a) the ability to react to T-cell mitogens in vitro is greater than in untreated nudes but lower than in normal mice; (b) the response to T-cell dependent antigens is less than normal; and (c) the rejection of skin grafts is slower than in normal animals. Whether host precursor cells which differentiate in an allogeneic thymus are able to reject skin grafts from thymus donor strain appears to depend on the strain combination used.
Retrovirus-Mediated Expression of E2A-PBX1 Blocks Lymphoid Fate but Permits Retention of Myeloid Potential in Early Hematopoietic Progenitors

The oncogenic transcription factor E2A-PBX1 is expressed consequent to chromosomal translocation 1;19 and is an important oncogenic driver in cases of pre-B-cell acute lymphoblastic leukemia (ALL). Elucidating the mechanism by which E2A-PBX1 induces lymphoid leukemia would be expedited by the availability of a tractable experimental model in which enforced expression of E2A-PBX1 in hematopoietic progenitors induces pre-B-cell ALL. However, hematopoietic reconstitution of irradiated mice with bone marrow infected with E2A-PBX1-expressing retroviruses consistently gives rise to myeloid, not lymphoid, leukemia. Here, we elucidate the hematopoietic consequences of forced E2A-PBX1 expression in primary murine hematopoietic progenitors. We show that introducing E2A-PBX1 into multipotent progenitors permits the retention of myeloid potential but imposes a dense barrier to lymphoid development prior to the common lymphoid progenitor stage, thus helping to explain the eventual development of myeloid, and not lymphoid, leukemia in transplanted mice. Our findings also indicate that E2A-PBX1 enforces the aberrant, persistent expression of some genes that would normally have been down-regulated in the subsequent course of hematopoietic maturation. We show that enforced expression of one such gene, Hoxa9, a proto-oncogene associated with myeloid leukemia, partially reproduces the phenotype produced by E2A-PBX1 itself. Existing evidence suggests that the 1;19 translocation event takes place in committed B-lymphoid progenitors. However, we find that retrovirus-enforced expression of E2A-PBX1 in committed pro-B-cells results in cell cycle arrest and apoptosis. Our findings indicate that the neoplastic phenotype induced by E2A-PBX1 is determined by the developmental stage of the cell into which the oncoprotein is introduced.
The structure of object transportation and orientation in human-computer interaction

An experiment was conducted to investigate the relationship between object transportation and object orientation by the human hand in the context of humancomputer interaction (HCI). This work merges two streams of research: the structure of interactive manipulation in HCI and the natural hand prehension in human motor control. It was found that object transportation and object orientation have a parallel, interdependent structure which is generally persistent over different visual feedback conditions. The notion of concurrency and interdependence of multidimensional visuomotor control structure can provide a new framework for human-computer interface evaluation and design.
NLP is a novel transcription regulator involved in VSG expression site control in Trypanosoma brucei

Trypanosoma brucei mono-allelically expresses one of approximately 1500 variant surface glycoprotein (VSG) genes while multiplying in the mammalian bloodstream. The active VSG is transcribed by RNA polymerase I in one of approximately 15 telomeric VSG expression sites (ESs). T. brucei is unusual in controlling gene expression predominantly post-transcriptionally, and how ESs are mono-allelically controlled remains a mystery. Here we identify a novel transcription regulator, which resembles a nucleoplasmin-like protein (NLP) with an AT-hook motif. NLP is key for ES control in bloodstream form T. brucei, as NLP knockdown results in 45- to 65-fold derepression of the silent VSG221 ES. NLP is also involved in repression of transcription in the inactive VSG Basic Copy arrays, minichromosomes and procyclin loci. NLP is shown to be enriched on the 177- and 50-bp simple sequence repeats, the non-transcribed regions around rDNA and procyclin, and both active and silent ESs. Blocking NLP synthesis leads to downregulation of the active ES, indicating that NLP plays a role in regulating appropriate levels of transcription of ESs in both their active and silent state. Discovery of the unusual transcription regulator NLP provides new insight into the factors that are critical for ES control.
Which Amount of BMI-SDS Reduction Is Necessary to Improve Cardiovascular Risk Factors in Overweight Children?

CONTEXT Knowing the changes of cardiovascular risk factors (CRFs) in relation to weight loss would be helpful to advise overweight children and their parents and to decide whether drugs should be prescribed in addition to lifestyle intervention. OBJECTIVE The objective of the study was to determine the body mass index (BMI)-SD score (SDS) reduction to improve CRFs in overweight children. DESIGN This was a prospective observation study. SETTING The study was conducted at a specialized outpatient obesity clinic. PATIENTS A total of 1388 overweight children (mean BMI 27.9 ± 0.1 kg/m(2), mean age 11.4 ± 0.1 y, 43.8% male, 45.5% prepubertal) participated in the study. INTERVENTION The study included a 1-year lifestyle intervention. MAIN OUTCOME MEASURES We studied changes of blood pressure (BP), fasting high-density lipoprotein- and low-density lipoprotein-cholesterol, triglycerides, glucose, and homeostasis model assessment (HOMA) of insulin resistance index. Change of weight status was determined by δBMI-SDS based on the recommended percentiles of the International Task Force of Obesity. RESULTS BMI-SDS change was associated with a significant improvement of all CRFs except fasting glucose and low-density lipoprotein-cholesterol after adjusting for multiple confounders such as baseline CRFs, age, gender, BMI, pubertal stage, and its changes. BMI-SDS reduction of 0.25-0.5 was related to a decrease of systolic blood pressure (BP) (-3.2 ± 1.4 mm Hg), diastolic BP (-2.2 ± 1.1 mm Hg), triglycerides (-6.9 ± 5.8 mg/dL), HOMA (-0.5 ± 0.3), and triglyceride/high-density lipoprotein)-cholesterol (-0.3 ± 0.2), whereas high-density lipoprotein (HDL)-cholesterol increased (+1.3 ± 1.2 mg/dL). A reduction of greater than 0.5 BMI-SDS led to more pronounced improvement (systolic BP -6.0± 1.3 mm Hg, diastolic BP -5.1 ± 1.3 mm Hg, triglycerides -16.4 ± 7.1 mg/dL, HDL-cholesterol +1.6 ± 1.5 mg/dL, HOMA -0.9 ± 0.3). Per 0.1 BMI-SDS reduction in systolic BP (-1.0 mm Hg), diastolic BP (-0.8 mm Hg), triglycerides (-2.3 mg/dL), HOMA (-0.2), and triglyceride/HDL-cholesterol (-0.5) decreased significantly, whereas HDL-cholesterol (0.2 mg/dL) increased significantly in linear regression analyses and accounted for multiple confounders. CONCLUSIONS A BMI-SDS reduction of 0.25 or greater significantly improved hypertension, hypertriglyceridemia, and low HDL-cholesterol, whereas a BMI-SDS greater than 0.5 doubled the effect.
High Intracellular Chloride Slows the Decay of Glycinergic Currents

The time course of currents mediated by native and recombinant glycine receptors was examined with a combination of rapid agonist applications to outside-out patches and single-channel recording. The deactivation time constant of currents evoked by brief, saturating pulses of glycine is profoundly affected by the chloride concentration on the intracellular side of the cell membrane. Deactivation was threefold slower when intracellular chloride was increased from a low level (10 mm), similar to that observed in living mature neurons, to 131 mm (“symmetrical” chloride, often used in pipette internal solutions). Single-channel analysis revealed that high chloride has its greatest effect on the channel closing rate, slowing it by a factor of 2 compared with the value we estimated in the cell-attached mode (in which the channels are at physiological intracellular chloride concentrations). The same effect of chloride was observed when glycinergic evoked synaptic currents were recorded from juvenile rat spinal motoneurons in vitro, because the decay time constant was reduced from ∼7 ms to ∼3 ms when cells were dialyzed with 10 mm chloride intracellular recording solution. Our results indicate that the time course of glycinergic synaptic inhibition in intact neurons is much faster than is estimated by measurements in symmetrical chloride and can be modulated by changes in intracellular chloride concentration in the range that can occur in physiological or pathological conditions.
Language Attitudes among Adolescents in Montreal: Potential Lessons for Language Planning in Québec

Over the last four decades, numerous laws have been implemented with the aim of strengthening the position of French in Quebec. Nevertheless, the French language remains threatened – firstly due to the status of English as the global lingua franca, and secondly due to its role as the language of upward mobility in North America at large. Consequently, there are ongoing debates regarding the need for new language planning measures to protect and promote French. Some of the most prominent proposals in the recent past intended to limit access to Quebec's English-speaking colleges d'enseignement general et professionnel, typically abbreviated to cegeps. The aim of these proposals was to prevent young francophones and allophones from integrating socially and professionally into the anglophone community. However, it was unclear whether such proposals would have the necessary attitudinal support at the grassroots level to be successful. This article thus presents the findings of a study which made use of a quest.
Role of organizational learning in strategic alliance

There are two main streams of research related to alliance performance. From economic sociology perspective, relational capital is the dyadic factor determines alliance performance. Strong relational capital leads to good alliance performance. From organizational learning theory or competence-based theory perspective, alliance capability is the firm’s ability to achieve good alliance performance. This paper introduces organizational learning as the intermediary of relational capital and alliance capability. In addition, this paper identifies four dimensions of alliance capability confined to organizational learning.
Content Validity and Psychometric Properties of the Nomination Scale for Identifying Football Talent (NSIFT): Application to Coaches, Parents and Players

The identification of football talent is a critical issue both for clubs and the families of players. However, despite its importance in a sporting, economic and social sense, there appears to be a lack of instruments that can reliably measure talent performance. The aim of this study was to design and validate the Nomination Scale for Identifying Football Talent (NSIFT), with the aim of optimising the processes for identifying said talent. The scale was first validated through expert judgment, and then statistically, by means of an exploratory factor analysis (EFA), confirmatory factor analysis (CFA), internal reliability and convergent validity. The results reveal the presence of three factors in the scale’s factor matrix, with these results being confirmed by the CFA. The scale revealed suitable internal reliability and homogeneity indices. Convergent validity showed that it is teammates who are best able to identify football talent, followed by coaches and parents. It can be concluded that the NSIFT is suitable for use in the football world. Future studies should seek to confirm these results in different contexts by means of further CFAs.
It ’ s All About Me : Narcissistic CEOs and Their Effects on Company Strategy and Performance

Our study extends upper-echelons theory by introducing CEO narcissism as a formal construct for explaining company strategy and performance. Drawing on psychological research indicating that narcissism is a personality dimension, rather than just a pathological disorder, we argue that narcissism in CEOs is positively related to strategic dynamism and grandiosity, and it engenders extreme and volatile organizational performance. We empirically study 111 CEOs in the computer and software industries, relying on six unobtrusive indicators of CEO narcissism. These indicators, which come from multiple sources, strongly cohere and allow us to develop a multi-item CEO narcissism index. We find considerable support for our hypotheses, indicating that CEOs vary in how narcissistic they are, and that these differences affect important organizational outcomes. We conclude the paper by suggesting future research on CEO narcissism.
Long-Term Stability and Dynamical Environment of the PSR 1257+12 Planetary System

We study the long-term dynamics of the PSR 1257+12 planetary system. Using the recently determined accurate initial condition by Konacki & Wolszczan, who derived the orbital inclinations and the absolute masses of planets B and C, we investigate the system stability by long-term, 1 Gyr direct integrations. No secular changes of the semimajor axes, eccentricities, and inclinations appear during such an interval. This stable behavior is confirmed with the fast indicator MEGNO. The analysis of the orbital stability in the neighborhood of the nominal initial condition reveals that the PSR 1257+12 system is localized in a wide stable region of the phase space but close to a few weak two- and three-body mean motion resonances. The long-term stability is additionally confirmed by a negligible exchange of the angular momentum deficit between the innermost planet A and the pair of outer planets B and C. An important feature of the system that helps sustain the stability is the secular apsidal resonance between planets B and C with the center of libration about 180°. We also find useful limits on the elements of the innermost planet A that are otherwise unconstrained by the observations. Specifically, we find that the line of nodes of planet A cannot be separated by more than about ±60° from the nodes of the bigger companions B and C. This limits the relative inclination of the orbit of planet A to the mean orbital plane of planets B and C to moderate values. We also perform a preliminary study of the short-term dynamics of massless particles in the system. We find that a relatively extended stable zone exists between planets A and B. Beyond planet C, the stable zone appears already at distances 0.5 AU from the parent star. For moderately low eccentricities beyond 1 AU, the motion of massless particles does not suffer from strong instabilities and this zone is basically stable, independent of the inclinations of the orbits of the test particles to the mean orbital plane of the system. This is an encouraging result supporting the search for a putative dust disk or a Kuiper Belt, especially with the Spitzer Space Telescope.
Social contacts and social isolation: A typology

This study explores a meaningful approach to the issue of social isolation. Although an approach to social isolation based on the personal support networks of individuals is still common, the authors prefer to explicitly incorporate two elements, an objective and a subjective criterion. Larger networks do contribute to people's subjective well-being, but there are many individuals who feel lonely despite their large networks, and vice versa. Based on two criteria, the network approach and the subjective feelings of well-being in terms of loneliness, a typology of social contacts has been designed. This approach was empirically explored in a sample of over 2,400 Dutch adults by assessing the relation with actual social support, which is an important function of social networks. The results show that the typology contains four main groups: the socially competent (64%), the socially inhibited (8%), the lonely (22%), and the socially isolated (6%). The typology gives a more differentiated picture of an individual's social support than an analysis based solely on a network or loneliness approach. A description is given of the main characteristics of the four groups in terms of network size, feelings of loneliness, social isolation risk factors, the balance in giving and receiving support, life events, personal competences and social responsibility. The four groups differ substantially and the risk of social isolation increases linearly: the socially competent are the best off, and the socially isolated the worst. The socially inhibited and the lonely occupy a position in between. The application of both criteria, loneliness and network size, seems to be a promising approach to the issue of social isolation