Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsα‐receptor interaction

Pseudohypoparathyroidism type Ia (PHPIa) is caused by GNAS mutations leading to deficiency of the α‐subunit of stimulatory G proteins (Gsα) that mediate signal transduction of G protein‐coupled receptors via cAMP. PHP type Ic (PHPIc) and PHPIa share clinical features of Albright hereditary osteodystrophy (AHO); however, in vitro activity of solubilized Gsα protein is normal in PHPIc but reduced in PHPIa. We screened 32 patients classified as PHPIc for GNAS mutations and identified three mutations (p.E392K, p.E392X, p.L388R) in four unrelated families. These and one novel mutation associated with PHPIa (p.L388P) were introduced into a pcDNA3.1(−) expression vector encoding Gsα wild‐type and expressed in a Gsα‐null cell line (GnasE2−/E2−). To investigate receptor‐mediated cAMP accumulation, we stimulated the endogenous expressed β2‐adrenergic receptor, or the coexpressed PTH or TSH receptors, and measured the synthesized cAMP by RIA. The results were compared to receptor‐independent cholera toxin‐induced cAMP accumulation. Each of the mutants associated with PHPIc significantly reduced or completely disrupted receptor‐mediated activation, but displayed normal receptor‐independent activation. In contrast, PHPIa associated p.L388P disrupted both receptor‐mediated activation and receptor‐independent activation. We present a new subgroup of PHP that is caused by Gsα deficiency and selectively affects receptor coupling functions of Gsα. Hum Mutat 32:1–8, 2011. © 2011 Wiley‐Liss, Inc.
Beta-Thalassemia in Iran: New Insight into the Role of Genetic Admixture and Migration

Iran with an area of 1.648 million km2 is located between the Caspian Sea and the Persian Gulf. The Iranian population consists of multiethnic groups that have been influenced by various invasions and migration throughout history. Studies have revealed the presence of more than 47 different β-globin gene mutations responsible for β-Thalassemia in Iran. This paper is an attempt to study the origin of β-Thalassemia mutations in different parts of Iran. Distribution of β-Thalassemia mutations in Iran shows different patterns in different areas. β-Thalassemia mutations have been a reflection of people and area in correlation with migration and origin of ancestors. We compared the frequencies of β-globin mutations in different regions of Iran with those derived from neighboring countries. The analysis provided evidence of complementary information about the genetic admixture and migration of some mutations, as well as the remarkable genetic classification of the Iranian people and ethnic groups.
Toxin Plasmids of Clostridium perfringens

SUMMARY In both humans and animals, Clostridium perfringens is an important cause of histotoxic infections and diseases originating in the intestines, such as enteritis and enterotoxemia. The virulence of this Gram-positive, anaerobic bacterium is heavily dependent upon its prolific toxin-producing ability. Many of the ∼16 toxins produced by C. perfringens are encoded by large plasmids that range in size from ∼45 kb to ∼140 kb. These plasmid-encoded toxins are often closely associated with mobile elements. A C. perfringens strain can carry up to three different toxin plasmids, with a single plasmid carrying up to three distinct toxin genes. Molecular Koch's postulate analyses have established the importance of several plasmid-encoded toxins when C. perfringens disease strains cause enteritis or enterotoxemias. Many toxin plasmids are closely related, suggesting a common evolutionary origin. In particular, most toxin plasmids and some antibiotic resistance plasmids of C. perfringens share an ∼35-kb region containing a Tn916-related conjugation locus named tcp (transfer of clostridial plasmids). This tcp locus can mediate highly efficient conjugative transfer of these toxin or resistance plasmids. For example, conjugative transfer of a toxin plasmid from an infecting strain to C. perfringens normal intestinal flora strains may help to amplify and prolong an infection. Therefore, the presence of toxin genes on conjugative plasmids, particularly in association with insertion sequences that may mobilize these toxin genes, likely provides C. perfringens with considerable virulence plasticity and adaptability when it causes diseases originating in the gastrointestinal tract.
Evaluation of integrated protected area management in Slovak national parks

National park management institutions must adapt as society’s goals and preferences change. This is especially true in countries that recently joined the European Union and have ungone rapid institution change. Tools for evaluating national park management are important for guiding such institutional changes. We evaluate the ability of the Integrated Protected Area Management (IPAM) toolbox to identify areas of management that should be targeted for improvement. We find that the IPAM toolbox breaks the complex task of protected area management into specific tangable action areas, and that IPAM assessment can aid managers in identifing specific areas of protected area management that need revisitng. We conduct an IPAM assessment for all nine Slovak national parks and identify commonalities among the assessment results. These commonalities point to necessary institutional changes beyond the control of individual park administrators. The IPAM toolbox is a useful tool to aid national protected area institutions adapt to changing social and environmental conditions. Ultimately, such adaptiation will lead to more efficent and effective park management.
The metacognitive functioning of middle school students with and without learning disabilities during mathematical problem solving

of a dissertation at the University of Miami. Dissertation supervised by Professor Marjorie Montague. No. of pages in text. (105) The purpose of this study was to investigate the metacognitive functioning of students with learning disabilities (LD), low-achieving (LA) students, and average-achieving (AA) students within the context of math problem solving. Metacognition, that is, the awareness individuals have regarding their own mental processes and ability to self-regulate performance, is an important predictor of learning. Deficits in metacognition have been attributed to an inability to effectively balance the cognitive and metacognitive strategies necessary for successful problem solving. Students with LD have considerable difficulty with self-regulation. This study investigates three components of metacognition: metacognitive knowledge, metacognitive experience, and metacognitive skills. The differences in these components among students with LD (n = 15), LA students (n = 38), and AA students (n = 29) and their influence on students’ math word problem solving was studied. Furthermore, the relationships among the three components of metacognition were investigated in the context of ability group differences. To assess metacognitive functioning, students were administered a structured interview and a survey and they solved three math word problems while thinking aloud. Additionally, to assess math problem-solving ability, students were administered a 10-item math word problem-solving test. Results indicated that students with LD demonstrated a different pattern of metacognitive function than AA students and LA students. Students across ability groups look relatively equivalent in the quantity of metacognitive skills. However, when discriminating between the type and quality of the metacognitive skills employed, ability group differences were evident. Ability group differences in metacognitive functioning emerged with respect to problem difficulty. The directions of the relationships among the components of metacognition were the same across ability groups. However, the magnitude and strength of the relationships differed by ability. Additionally, metacognitive knowledge was a significant predictor of math word problem-solving performance for AA students, but not for the other ability groups. Furthermore, there was a significant difference in the relationship between metacognitive experience and math word problem solving for students with LD and AA students. Educational implications are discussed for teaching students to use metacognition during problem solving.
Targeting of the Arf-GEF GBF1 to lipid droplets and Golgi membranes

Summary Lipid droplet metabolism and secretory pathway trafficking both require activation of the Arf1 small G protein. The spatiotemporal regulation of Arf1 activation is mediated by guanine nucleotide exchange factors (GEFs) of the GBF and BIG families, but the mechanisms of their localization to multiple sites within cells are poorly understood. Here we show that GBF1 has a lipid-binding domain (HDS1) immediately downstream of the catalytic Sec7 domain, which mediates association with both lipid droplets and Golgi membranes in cells, and with bilayer liposomes and artificial droplets in vitro. An amphipathic helix within HDS1 is necessary and sufficient for lipid binding, both in vitro and in cells. The HDS1 domain of GBF1 is stably associated with lipid droplets in cells, and the catalytic Sec7 domain inhibits this potent lipid-droplet-binding capacity. Additional sequences upstream of the Sec7 domain–HDS1 tandem are required for localization to Golgi membranes. This mechanism provides insight into crosstalk between lipid droplet function and secretory trafficking.
The construction of a common identity through online discourse: a socio-cultural study of a virtual community

This thesis investigates the relationship between identity and discourse in a networked collaborative environment in order to explore the following question: Is the construction of a common identity taking place? The research question draws on the socio-cultural theory and, in particular, on the view according to which the development of a common identity is an important dimension of learning. More specifically, the thesis builds upon recent criticism attracted by the sociocultural notion of ―Community of Practice‖ for its inadequate account of the relationship between identity, language and practice, both in traditional and computer-mediated settings. The empirical section of the thesis reports a study which applies the concept of recognition work developed by James Gee to the discursive dynamics identified in a ―discussion room‖ of an Italian online community of young psychologists and psychology students. In the study, discourse analysis was carried out on 20 online discussions and on 23 semi-structured interviews. The findings demonstrate that the notion of recognition work can be used to study how identities are constructed and negotiated through discourse, and provide an additional insight into the role of computer-mediated communication in the relationship between identity and learning. The findings also have theoretical implications, raising the question as to whether the emphasis on communities of practice has exhausted its possible contributions to a socio-cultural theory of learning. Additionally, the thesis also considers the implications for the design of virtual learning environments that try to foster collaborative learning through networked discourse.
Convergence in the Financial Services Industry

The ®nancial services industry is undergoing drastic changes. One of the main challenges for managers of ®nancial institutions as well as for regulators and supervisors is the growing convergence between different sectors within the ®nancial services industry. In this paper, we present some general observations and recommendations. We hope that these recommendations help in fostering innovation and prosperity, without neglecting the important conditions of a stable and reliable ®nancial sector. This is an important message to both supervisors and regulators in the ®nancial services industry. An optimal regulation and supervision can only be guaranteed if there is a good balance between the measures to guarantee a stable and reliable ®nancial sector on the one hand and the need for safeguarding suf®cient competition and innovation on the other hand. This is not a simple task, especially because there is no single answer to this complex equilibrium. However, adequate regulation and supervision is only possible if there is a clear understanding of the market reality. There, regulators and supervisors will have to accept that they will always ` lag behind'' the business innovations, and that market forces will always try to ®nd ways to circumvent (restrictive) legislation. The ®nancial convergence is, as we will show later, a perfect example in this respect.
The health status and life satisfaction of first‐year medical students

The self-reported health status and life satisfaction of 286 first-year Duke University medical students in four consecutive classes were measured at the beginning and end of the school year and compared statistically with relevant sociodemographic and behavioral factors. Health status, quantitated in terms of Duke Health Profile scores, was generally lower for women than for men. Although there was a definite trend of worsening along all parameters of health and satisfaction during the year for both women and men, the most marked change was the increase in depressive symptoms. The students who were very satisfied with life had fewer symptoms of depression and anxiety; higher self-esteem, better physical, mental, and social health; stronger social ties; more physical activity; more sleep; and fewer stressful life events. Strong social ties was the factor most positively related to better health and life satisfaction.
Comment: Isolation and Screening of Bacteria for Their Diazotrophic Potential and Their Influence on Growth Promotion of Maize Seedlings in Greenhouses

Maize Seedlings in Greenhouses. Recent papers by Kifle and Laing showed that diazotrophs isolated from Maize tissue and Maize-associated soil have the potential to promote growth of this important crop when used to inoculate seeds prior to planting (Kifle and Laing, 2016a,b). The fact that the authors focused their studies on diazotrophs presumes that the biological nitrogen fixation (BNF) is key to the mechanism of plant growth promotion by the microorganisms they tested. However, numerous other studies (e.g., Khalid et al., 2004) have found plant growth promotion by organisms isolated from the rhizosphere that were not screened for BNF, implying that this trait is not necessarily the key mechanism of plant growth promotion. By conducting additional analysis of their data, we find the striking result that rates of acetylene reduction in pure culture presented by Kifle and Laing (2016a) show a strong positive relationship with two metrics of plant health measured in their greenhouse experiment: chlorophyll content (Figure 1A) and stomatal conductance (Figure 1B). The acetylene reduction assay as conducted by Kifle and Laing (2016a) should serve as a proxy for maximum potential rates of BNF achievable by the diazotrophs they investigated. The relationships shown in Figures 1A,B therefore lend credence to the argument that BNF plays an important role in plant growth promotion by the microbes that Kifle and Laing (2016a) tested. By omitting fixed nitrogen sources from their fertilization regime, Kifle and Laing (2016a) designed their diazotroph inoculation experiment to investigate the direct role of BNF in plant growth promotion. Indeed, studies using stable isotope tracers have shown that nitrogen fixed by diazotrophic inoculants was incorporated into plant biomass. For example, Zakry et al. (2012) used the 15 N pool dilution technique to show that Oil Palm plants inoculated with the endophyte Bacillus sphaericus UPMB-10 obtained the majority of their nitrogen from fixation after 8 months of growth, while Knoth et al. (2014) found similar results for Poplar plants inoculated with multi-strain diazotrophic consortia. However, bacteria are known to promote plant growth through multiple other mechanisms besides diazotrophy (Friesen et al., 2011) and these mechanisms, which we outline below, may be at least partially responsible for the relationships presented in Figure 1 as well. Bacteria may increase nitrogen concentrations without diazotrophy through exoezyme release (e.g., Wallenstein and Weintraub, 2008). Rhizosphere bacteria may also enhance plant growth by altering the availability of nutrients other than nitrogen, such as through …
Economic Potentials of Women in Small-scale Fisheries in West Africa

In the past three and a half a century since fisheries development was embarked upon in West Africa, the significant contributions of women in sustaining the socio-economic livelihoods of their families has been neglected and taken for granted. Development and support systems have paid much less attention to the economic potentials of women in small-scale fisheries in West Africa. Women in developing economies, especially in Africa lack a ccess to services such as credit, fisheries extension, technology, information and basic education which are critical for shifting patterns of fisheries production or increasing output, all these are limited. Research information on the role and extent of women's involvement in agricultural and/or fisheries development process show a genuine desire to improve their socio-economic status. However, by a combination of factors, women could not break through the cycle of poverty. There is therefore need for the support systems to be organized in a way that should bring about social changes that may be resisted at first, but will eventually promote the role of women in the economy. Gender relations should not be seen as competitive but rather as complementary and mutually reinforcing. General recommendations include: training and extension programmes in fisheries targeting women in areas where they contribute to fisheries activities like processing, packaging, distribution and marketing; microcredit programmes to benefit women; networks formed at national level with the active participation of all the stakeholders.
Constructing entrepreneurial orientation in a selling context : the qualitative attitude approach

This paper explores the construction of attitudes in argumentative talk to underscore the context-specific nature of the dimensions of entrepreneurial orientation (EO) and their interrelations. The material comprises interviews in which the directors, who form the management group of a Finnish firm, individually commented on a statement that each sales-person is an autonomous entrepreneur'. Our analysis identified two opposing evaluations of entrepreneurial autonomy, which were labeled as proactive selling and internal competitive aggressiveness. The analysis points out limitations on the realistic and positivist premises of the conventional EO measures by identifying related yet differing understandings which actors involved in everyday organizational practices display in their talk. (original abstract)
On the Robustness of the Acoustic Scale in the Low-Redshift Clustering of Matter

We discuss the effects of nonlinear structure formation on the signature of acoustic oscillations in the late-time galaxy distribution. We argue that the dominant nonlinear effect is the differential motion of pairs of tracers separated by 150 Mpc. These motions are driven by bulk flows and cluster formation and are much smaller than the acoustic scale itself. We present a model for the nonlinear evolution based on the distribution of pairwise Lagrangian displacements that provides a quantitative model for the degradation of the acoustic signature, even for biased tracers in redshift space. The Lagrangian displacement distribution can be calibrated with a significantly smaller set of simulations than would be needed to construct a precise power spectrum. By connecting the acoustic signature in the Fourier basis with that in the configuration basis, we show that the acoustic signature is more robust than the usual Fourier-space intuition would suggest, because the beat frequency between the peaks and troughs of the acoustic oscillations is a very small wavenumber that is well inside the linear regime. We argue that any possible shift of the acoustic scale is related to infall on a scale of 150 Mpc, which is O(0.5%) fractionally at first order, even at z = 0. For the matter, there is a first-order cancellation such that the mean shift is O(10-4). However, galaxy bias can circumvent this cancellation and produce a subpercent systematic bias.
High-level separation logic for low-level code

Separation logic is a powerful tool for reasoning about structured, imperative programs that manipulate pointers. However, its application to unstructured, lower-level languages such as assembly language or machine code remains challenging. In this paper we describe a separation logic tailored for this purpose that we have applied to x86 machine-code programs. The logic is built from an assertion logic on machine states over which we construct a specification logic that encapsulates uses of frames and step indexing. The traditional notion of Hoare triple is not applicable directly to unstructured machine code, where code and data are mixed together and programs do not in general run to completion, so instead we adopt a continuation-passing style of specification with preconditions alone. Nevertheless, the range of primitives provided by the specification logic, which include a higher-order frame connective, a novel read-only frame connective, and a 'later' modality, support the definition of derived forms to support structured-programming-style reasoning for common cases, in which standard rules for Hoare triples are derived as lemmas. Furthermore, our encoding of scoped assembly-language labels lets us give definitions and proof rules for powerful assembly-language 'macros' such as while loops, conditionals and procedures. We have applied the framework to a model of sequential x86 machine code built entirely within the Coq proof assistant, including tactic support based on computational reflection.
Using Predicted Outcome Stratified Sampling to Reduce the Variability in Predictive Performance of a One-Shot Train-and-Test Split for Individual Customer Predictions

Since it is generally recognized that models evaluated on the data that was used for constructing them are overly optimistic, in predictive modeling practice, the assessment of a model’s predictive performance frequently relies on a one-shot train-and-test split between observations used for estimating a model, and those used for validating it. Previous research has indicated the usefulness of stratified sampling for reducing the variation in predictive performance in a linear regression application. In this paper, we validate the previous findings on six real-life European predictive modeling applications for marketing and credit scoring using a dichotomous outcome variable. We find confirmation for the reduction in variability using a procedure we describe as predicted outcome stratified sampling in a logistic regression model, and we find that the gain in variation reduction is – also in large data sets – almost always significant, and in certain applications markedly high.