Miracle-dz/UniFAR-FTUs huggingface dataset:
A simple ligand that selectively targets CUG trinucleotide repeats and inhibits MBNL protein binding

This work describes the rational design, synthesis, and study of a ligand that selectively complexes CUG repeats in RNA (and CTG repeats in DNA) with high nanomolar affinity. This sequence is considered a causative agent of myotonic dystrophy type 1 (DM1) because of its ability to sequester muscleblind-like (MBNL) proteins. Ligand 1 was synthesized in two steps from commercially available compounds, and its binding to CTG and CUG repeats in oligonucleotides studied. Isothermal titration calorimetry studies of 1 with various sequences showed a preference toward the T-T mismatch (Kd of 390 ± 80 nM) with a 13-, 169-, and 85-fold reduction in affinity toward single C-C, A-A, and G-G mismatches, respectively. Binding and Job analysis of 1 to multiple CTG step sequences revealed high affinity binding to every other T-T mismatch with negative cooperativity for proximal T-T mismatches. The affinity of 1 for a (CUG)4 step provided a Kd of 430 nM with a binding stoichiometry of 1:1. The preference for the U-U in RNA was maintained with a 6-, >143-, and >143-fold reduction in affinity toward single C-C, A-A, and G-G mismatches, respectively. Ligand 1 destabilized the complexes formed between MBNL1N and (CUG)4 and (CUG)12 with IC50 values of 52 ± 20 μM and 46 ± 7 μM, respectively, and Ki values of 6 ± 2 μM and 7 ± 1 μM, respectively. These values were only minimally altered by the addition of competitor tRNA. Ligand 1 does not destabilize the unrelated RNA-protein complexes the U1A-SL2 RNA complex and the Sex lethal-tra RNA complex. Thus, ligand 1 selectively destabilizes the MBNL1N-poly(CUG) complex.
Coupled and decoupled impedance models compared in power electronics systems

This paper provides a comparative analysis of impedance models for power electronic converters and systems for the purpose of stability investigations. Such models can be divided into either decoupled models or matrix models. A decoupled impedance model is highly appealing since the Single-Input-Single-Output (SISO) structure makes the analysis and result interpretation very simple. On the other hand, matrix impedance models are more accurate, and in some cases necessary. Previous works have applied various approximations to obtain decoupled models, and both the dq- and sequence domains have been used. This paper introduces the terms decoupled and semi-decoupled impedance models in order to have a clear classification of the available approximations. The accuracy of 4 decoupled impedance models are discussed based on the concept of Mirror Frequency Coupling (MFC). By definition the decoupled models based on sequence domain impedances will be exact for systems without MFC. In the general case, they are expected to be more accurate than the decoupled dq-impedance models. The paper defines a norm $\epsilon$ to measure the degree of coupling in the impedance matrices. This norm equals the error in the eigenvalue loci between the matrix and semi-decoupled models. This can also be viewed as the error in the semi-decoupled Nyquist plot. An example case study consisting of a grid-connected VSC with current controller and PLL is used to compare the different methods. It is found that decoupled and semi-decoupled models in the dq-domain are only applicable in grids with very low X/R-ratio. Furthermore, it is concluded that the decoupled model in the sequence domain gives close to equal results as the semi-decoupled model.
PHYSICAL ACTIVITY PATTERNS OF ADOLESCENTS WITH LONG TERM ILLNESSES OR DISABILITIES IN FINNISH GENERAL EDUCATION

Physical activity (PA) of adolescents with long term illnesses or disabilities (LTID) in general education is examined to provide evidence of PA levels from specific population groups. This study describes the PA levels of adolescents with LTID based on recommendations of daily 60mins of moderate-to-vigorous PA (MVPA) and vigorous leisure time PA (VPA) of at least two times a week for at least one hour per week. Finnish data from the Health Behaviour in School-aged Children (HBSC) study was pooled from 2002 and 2010 surveys. 1126 respondents (14.6%) self-reported as having a LTID and details of main categories of LTID were used to examine PA behaviours. Overall, 15.6% of adolescents with LTID reported daily MVPA. In their leisure time, 74.0% of adolescents with LTID had met the VPA recommendation. These figures are lower than other reported literature on PA amongst adolescents. PA of adolescents with LTID in general education can be seen as a complex collection of different categories. Boys were more active than girls. Younger adolescents were more active than older. A closer look into the many domains of LTID demonstrated how various LTID groups differ and share similar PA patterns.
International Patterns in Principal Preparation: Commonalities and Variations in Pre-service Programmes

This article illuminates major features of high-quality leadership programmes across different education systems. We do so by focusing on capturing commonalities and variations in high-quality pre-service programmes from five differing societies, all of which are high-performing education systems. To this end, we first delineate key profiles of each programme. Based on that, we discuss commonalities and variations in leadership programmes in terms of framework, content and operational features. Finally, we flesh out important implications for policy and practice.
Lipoprotein lipase mRNA expression in whole blood is a prognostic marker in B cell chronic lymphocytic leukemia.

BACKGROUND Chronic lymphocytic leukemia (CLL) is characterized by high individual variability in clinical course and the need for therapy. Differentiation of prognostic subgroups is based primarily on the mutation status of the genes for the variable region of the immunoglobulin heavy chain (IGHV). The time- and labor-intensive nature of this analysis necessitates the use of easily applicable surrogate markers. METHODS We developed a quantitative PCR (qPCR) method for determining lipoprotein lipase (LPL) mRNA expression and analyzed samples of lysed whole blood and CD19-selected cells from 50 CLL patients. Associations of LPL and ZAP70 [zeta-chain (TCR) associated protein kinase 70 kDa] expression with IGHV mutation status, overall survival (OS), and treatment-free survival (TFS) were investigated. RESULTS Lysed samples of whole blood and CD19-selected cells were similar with respect to LPL expression (R = 0.88; P <0.0001). LPL expression was significantly associated with IGHV mutation status [chi(2)(1) = 15.3; P <0.0001] and showed an 89.3% specificity, a 68.2% sensitivity, an 83.3% positive predictive value, and a 78.1% negative predictive value for IGHV mutation status. LPL expression was significantly associated with both OS and TFS in log-rank tests (both P values = 0.002). LPL-positive patients had a significantly shorter median TFS time (23 months) than LPL-negative patients (88 months) (P = 0.002). CONCLUSIONS LPL mRNA expression is a valuable prognostic marker in CLL. The method does not require cell purification, and its applicability with archived samples facilitates its use in the clinical routine and other studies.
A comparison of salivary pH in sympatric wild lemurs (Lemur catta and Propithecus verreauxi) at Beza Mahafaly Special Reserve, Madagascar

Chemical deterioration of teeth is common among modern humans, and has been suggested for some extinct primates. Dental erosion caused by acidic foods may also obscure microwear signals of mechanical food properties. Ring‐tailed lemurs at the Beza Mahafaly Special Reserve (BMSR), Madagascar, display frequent severe tooth wear and subsequent tooth loss. In contrast, sympatric Verreaux's sifaka display far less tooth wear and infrequent tooth loss, despite both species regularly consuming acidic tamarind fruit. We investigated the potential impact of dietary acidity on tooth wear, collecting data on salivary pH from both species, as well as salivary pH from ring‐tailed lemurs at Tsimanampesotse National Park, Madagascar. We also collected salivary pH data from ring‐tailed lemurs at the Indianapolis Zoo, none of which had eaten for at least 12 hr before data collection. Mean salivary pH for the BMSR ring‐tailed lemurs (8.098, n=41, SD=0.550) was significantly more alkaline than Verreaux's sifaka (7.481, n=26, SD=0.458). The mean salivary pH of BMSR (8.098) and Tsimanampesotse (8.080, n=25, SD=0.746) ring‐tailed lemurs did not differ significantly. Salivary pH for the Indianapolis Zoo sample (8.125, n=16, SD=0.289) did not differ significantly from either the BMSR or Tsimanampesotse ring‐tailed lemurs, but was significantly more alkaline than the BMSR Verreaux's sifaka sample. Regardless of the time between feeding and collection of pH data (from several minutes to nearly 1 hr), salivary pH for each wild lemur was above the “critical” pH of 5.5, below which enamel demineralization occurs. Thus, the high pH of lemur saliva suggests a strong buffering capacity, indicating the impact of acidic foods on dental wear is short‐lived, likely having a limited effect. However, tannins in tamarind fruit may increase friction between teeth, thereby increasing attrition and wear in lemurs. These data also suggest that salivary pH varies between lemur species, corresponding to broad dietary categories. Am. J. Primatol. 70:363–371, 2008. © 2007 Wiley‐Liss, Inc.
PATHOGENESIS OF TYPE 2 DIABETES AND INSULIN RESISTANCE ( RM WATANABE , SECTION EDITOR ) Lipotoxicity in the Pancreatic Beta Cell : Not Just Survival and Function , but Proliferation as Well ?

Free fatty acids (FFAs) exert both positive and negative effects on beta cell survival and insulin secretory function, depending on concentration, duration, and glucose abundance. Lipid signals are mediated not only through metabolic pathways, but also through cell surface and nuclear receptors. Toxicity is modulated by positive signals arising from circulating factors such as hormones, growth factors and incretins, as well as negative signals such as inflammatory mediators and cytokines. Intracellular mechanisms of lipotoxicity include metabolic interference and cellular stress responses such as oxidative stress, endoplasmic reticulum (ER) stress, and possibly autophagy. New findings strengthen an old hypothesis that lipids may also impair compensatory beta cell proliferation. Clinical observations continue to support a role for lipid biology in the risk and progression of both type 1 (T1D) and type 2 diabetes (T2D). This review summarizes recent work in this important, rapidly evolving field.
Colorimetric sensor for label free detection of porcine PCR product

Selective detection of specific DNA sequences is increasingly getting momentum in clinical diagnosis, pathology, genetics [1–3] and food analysis [4, 5]. The polymerase chain reaction (PCR) is a commonly used technique to amplify specific sequence segment in nearly all DNA-based assays [3]. The use of PCR addresses both the sensitivity issues and sample purification steps producing a large quantity DNA from as little as single copy. However, post- PCR analysis of PCR amplified DNA involves complex and time consuming electrophoresis, blot analysis or sequencing [3].
Iterative Methods for Nonlinear Equations or Systems and Their Applications 2014

The guest editors would like to express their gratitude to all those who submitted papers for publication and to the many reviewers whose reports were essential for us. We would also like to thank the editorial board members of this journal. Alicia Cordero and Juan R. Torregrosa were partially supported by Ministerio de Ciencia y Tecnologa MTM2011-28636-C02-02.
A Dimensional Analysis of the Relationship between Psychological Empowerment and Effectiveness Satisfaction, and Strain

This paper examines the contribution of each of the four dimensions in Thomas and Velthouse’s (1990) multidimensional conceptualization of psychological empowerment in predicting three expected outcomes of empowerment: effectiveness, work satisfaction, and job-related strain. The literature on the four dimensions of empowerment (i.e., meaning, competence, self-determination, and impact) is reviewed and theoretical logic is developed linking the dimensions to specific outcomes. The expected relationships are tested on a sample of managers from diverse units of a manufacturing organization and then replicated on an independent sample of lower-level employees in a service organization using alternative measures of the outcome variables. The results, largely consistent across the two samples, suggest that different dimensions are related to different outcomes and that no single dimension predicts all three outcomes. These results indicate that employees need to experience each of the empowerment dimensions in order to achieve all of the hoped for outcomes of empowerment.
Negotiating the role of expert carers on an adult hospital ward

Contemporary systems of welfare are increasingly underpinned by the assumption that families should care for their dependent adult relatives. Yet, the burgeoning empirical literature in this area has given little attention to the ways in which family caregivers fit into the service system. Drawing on interactionist theories of the division of labour, this paper employs ethnographic data, taken from a recent study, to explore the ways in which formal and informal carers negotiate ‘care’ on an adult medical ward. It is argued that established family carers (referred to as expert carers) constitute a special case in understanding the negotiation of care in the hospital context because of the challenge they pose to fundamental features of the social organisation of the work: nurses’ control over caring processes, their claim to expertise and their license to define standards of care.
Gobierno electrónico y transparencia financiera y presupuestal de los departamentos en Colombia

El gobierno electronico viene siendo promovido como un instrumento de modernizacion, que mejora la transparencia y la divulgacion de la informacion financiera y presupuestal de las entidades publicas. En la ultima decada, el e-government ha sido implementado en las entidades gubernamen- tales latinoamericanas del orden nacional y territorial, por lo que conviene evaluar su grado de avance. El objetivo de este trabajo es evaluar el nivel de divulgacion de la informacion financiera y presupuestal de la administracion territorial en Colombia (los departamentos) por medio de Internet, asi como identificar las variables que influyen en tales niveles de divulgacion. Para ello se utiliza el in- dice planteado por Caba et al., (2008), ajustado al contexto colombiano. Se miden los niveles de transparencia de 33 departamentos y se identifican, por medio de regresiones, las variables financi- eras y socioeconomicas que explican los niveles observados. Los resultados muestran que el nivel de divulgacion de los departamentos es bajo comparado con la informacion dispuesta en Internet por el gobierno nacional. Se ha encontrado que el tamano de la poblacion, el acceso a Internet, el apalan - camiento y el estres financiero, se relacionan significativamente con la divulgacion por parte de los departamentos
Prediction of ovarian hyperstimulation syndrome in coasted patients in an IVF/ICSI program

AIM: To determine why a subgroup of coasted patients developed moderate/severe ovarian hyperstimulation syndrome (OHSS) in an assisted reproduction setting. MATERIALS AND METHODS: Retrospective study of 2948 in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycles with 327 patients requiring coasting. Long protocol gonadotrophin releasing hormone analogue (GnRH-a) regimen was used and serum estradiol (E2) checked when ≥20 follicles were noted on follicular tracking. Coasting was initiated when leading three follicles were ≥15mm with E2 ≥1635pg/ml. RESULTS: The incidence of moderate/severe OHSS was 10.4% in coasted patients (equivalent 1.15% of the total IVF/ICSI cycles in the Center). Coasted patients who subsequently developed OHSS showed a significantly higher number of retrieved oocytes, higher serum E2 level on the day of human chorionic gonadotrophin (hCG) administration, and multiple pregnancies. No significant differences were noted with female age, BMI, cause of infertility, gonadotrophin dosage, coasting duration, and % of E2 drop. CONCLUSION: Moderate/severe OHSS might be predicted in coasted patients by a combination of total oocyte numbers and E2 level on the day of hCG. Multiple pregnancies also significantly increased the risk.
Role of Cellular Glycosaminoglycans and Charged Regions of Viral G Protein in Human Metapneumovirus Infection

ABSTRACT Human metapneumovirus (hMPV) is an important cause of lower respiratory tract disease, particularly in infants and young children. hMPV has two major glycoproteins, G and F, which are responsible for virus attachment and membrane fusion, respectively. We investigated the role of cellular glycosaminoglycans (GAGs) and G protein in hMPV infection. The pretreatment of hMPV with soluble heparin markedly inhibited the infection of HEp-2 cells. Recombinant G protein, comprising the extracellular domain of G, bound to heparin-agarose columns and also to HEp-2 cells. hMPV infection and G protein binding to HEp-2 cells was inhibited by other soluble GAGs, including chondroitin sulfates, by the enzymatic removal of cell surface GAGs with GAG lyases or by the pretreatment of cells with basic fibroblast growth factor. The role of cellular GAGs was confirmed by the binding of G protein to wild-type CHO cells but not to GAG-deficient CHO-pgsA745 cells. An analysis of the G protein sequence revealed two adjacent clusters of positively charged amino acids (149EKKKTRA155 and 159QRRGKGKE166). Truncated G fragments were expressed, and only the fragment containing these putative heparin binding domains retained heparin binding. The alanine mutagenesis of charged residues in either of these regions resulted in the loss of binding to heparin and to HEp-2 cells, suggesting that both sites are likely to be required for hMPV attachment. These results, taken together with the inhibition of hMPV infection by soluble G protein, indicate an important role for G protein and cellular GAGs in hMPV infection.
A streptococcal NRAMP homologue is crucial for the survival of Streptococcus agalactiae under low pH conditions

Streptococcus agalactiae or Group B Streptococcus (GBS) is a commensal bacterium of the human gastrointestinal and urogenital tracts as well as a leading cause of neonatal sepsis, pneumonia and meningitis. Maternal vaginal carriage is the main source for GBS transmission and thus the most important risk factor for neonatal disease. Several studies in eukaryotes identified a group of proteins natural resistance‐associated macrophage protein (NRAMP) that function as divalent cation transporters for Fe2+ and Mn2+ and confer on macrophages the ability to control replication of bacterial pathogens. Genome sequencing predicted potential NRAMP homologues in several prokaryotes. Here we describe for the first time, a pH‐regulated NRAMP Mn2+/Fe2+ transporter in GBS, designated MntH, which confers resistance to reactive oxygen species (ROS) and is crucial for bacterial growth and survival under low pH conditions. Our investigation implicates MntH as an important colonization determinant for GBS in the maternal vagina as it helps bacteria to adapt to the harsh acidic environment, facilitates bacterial adherence, contributes to the coexistence with the vaginal microbiota and plays a role in GBS intracellular survival inside macrophages.
STEREO VISION-BASED FORWARD OBSTACLE DETECTION

This paper proposes a stereo vision-based forward obstacle detection and distance measurement method. In general, stereo vision-based obstacle detection methods in automotive applications can be classified into two categories: IPM (Inverse Perspective Mapping)-based and disparity histogram-based. The existing disparity histogram-based method was developed for stop-and-go applications. The proposed method extends the scope of the disparity histogram-based method to highway applications by 1) replacing the fixed rectangular ROI (Region Of Interest) with the traveling lanebased ROI, and 2) replacing the peak detection with a constant threshold with peak detection using the threshold-line and peakness evaluation. In order to increase the true positive rate while decreasing the false positive rate, multiple candidate peaks were generated and then verified by the edge feature correlation method. By testing the proposed method with images captured on the highway, it was shown that the proposed method was able to overcome problems in previous implementations while being applied successfully to highway collision warning/avoidance conditions. In addition, comparisons with laser radar showed that vision sensors with a wider FOV (Field Of View) provided faster responses to cutting-in vehicles. Finally, we integrated the proposed method into a longitudinal collision avoidance system. Experimental results showed that activated braking by risk assessment using the state of the ego-vehicle and measuring the distance to upcoming obstacles could successfully prevent collisions.
Using behavioural insights to improve the public’s use of cyber security best practices

The aim of this project was to apply social and behavioural insights to cyber security challenges to answer the following questions: - What behaviours should people display to reduce their vulnerability to cyber-security attacks? - Why do people not behave securely online? - What can theories of behaviour tell us about how to effectively influence behaviour? - What is the role of communication campaigns in changing behaviour? - How can interventions be designed to motivate appropriate cyber-security behaviour? To achieve this, we adopted a Rapid Evidence Assessment of the literature on cybersecurity behaviours and interventions. We drew on the existing literature from science communication, health, social and organisational psychology and cyber security. We then carried out a brief email Delphi with experts in Cyber Security. We used this study to get expert opinion on the conclusions we had drawn from the literature. It should be noted that research into human aspects of cyber-security is piecemeal and nonsystematic. It relies heavily on self reported behaviours and beliefs which are not always reliable. Actual experimental studies have limitations of small sample size and homogenous, mainly student, populations. It is also worth noting that the rate of change of technology and uptake of the internet makes it difficult to draw conclusions from older research. However, suffice to say, there is sufficient evidence to say there is room for improvement in people’s cyber-security related behaviours.
Bayesian Optimization Algorithm, Population Sizing, and Time to Convergence

This paper analyzes convergence properties of the Bayesian optimization algorithm (BOA). It settles the BOA into the framework of problem decomposition used frequently in order to model and understand the behavior of simple genetic algorithms. The growth of the population size and the number of generations until convergence with respect to the size of a problem are theoretically-analyzed. The theoretical results are supported by a number of experiments.