Miracle-dz/UniFAR-FTUs huggingface dataset:
Low-dose fenfluramine in the treatment of neurologic disorders: experience in Dravet syndrome

In this paper, we review the experience with fenfluramine in epileptic and other paroxysmal disorders. Since the best available data are from the treatment of Dravet syndrome, we will focus primarily on this condition. Originally fenfluramine was launched as an anorectic agent. As early as 1985, seizure reduction in children could be demonstrated in a few cases with photosensitive, self-induced epilepsy. Hereafter, a small study was launched in patients with self-induced epilepsy. Results showed a significant seizure reduction, and review of the patient data showed that 5 of the 12 patients had Dravet syndrome. During that observation period, fenfluramine was withdrawn from the market because of cardiovascular side effects associated with prescribing higher doses in combination with phentermine for weight loss. In March 2002, a Belgian Royal Decree was issued permitting further study of fenfluramine in pediatric patients with intractable epilepsy. In 2011 under the Royal Decree, a prospective study of patients with Dravet syndrome treated with low-dose fenfluramine was initiated and is currently ongoing. The initial results are promising in terms of reduction of seizure frequency and overall tolerability.
Biochemical Analysis of Mutant T7 Primase/Helicase Proteins Defective in DNA Binding, Nucleotide Hydrolysis, and the Coupling of Hydrolysis with DNA Unwinding*

We characterized nine helicase-deficient mutants of bacteriophage T7 helicase-primase protein (4A′) prepared by random mutagenesis as reported in the accompanying paper (Rosenberg, A. H., Griffin, K., Washington, M. T., Patel, S. S., and Studier, F. W. (1996) J. Biol. Chem. 271, 26819-26824). Mutants were selected from each of the helicase-conserved motifs for detailed analysis to understand better their function. In agreement with the in vivo results, the mutants were defective in helicase activity but were active in primase function. dTTP hydrolysis, DNA binding, and hexamer formation were examined. Three classes of defective mutants were observed. Group A mutants (E348K, D424N, and S496F), defective in dTTP hydrolysis, lie in motifs 1a, 2, and 4 and are possibly involved in NTP binding/hydrolysis. Group B mutants (R487C and G488D), defective in DNA binding, lie in motif 4 and are responsible directly or indirectly for DNA binding. Group C mutants (G116D, A257T, S345F, and G451E) were not defective in any of the activities except the helicase function. These mutants, scattered throughout the protein, appear defective in coupling dTTPase activity to helicase function. Secondary structural predictions of 4A′ and DnaB helicases resemble the known structures of RecA and F1-ATPase enzymes. Alignment shows a striking correlation in the positions of the amino acids that interact with NTP and DNA.
Induction of cytotoxic T lymphocytes by intramuscular immunization with plasmid DNA is facilitated by bone marrow-derived cells.

Striated muscle is the predominant site of gene expression after i.m. immunization of plasmid DNA, but it is not clear if myocytes or professional antigen-presenting cells (APCs) of hematopoietic origin present the encoded antigens to class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL). To address this issue, CTL responses were assessed in mice engrafted with immune systems that were partially MHC matched with antigen-producing muscle cells. Spleen cells (sc) from immunocompetent F1 H-2bxd mice were infused into H-2b or H-2d mice carrying the severe combined immunodeficiency (scid) mutation, creating F1sc-->H-2b and F1sc-->H-2d chimeras, respectively. Immunization with DNA plasmids encoding the herpes simplex virus gB or the human immunodeficiency virus gp120 glycoproteins elicited antiviral CTL activity. F1sc-->H-2d chimeras responded to an H-2d-restricted gp120 epitope but not an H-2b restricted gB epitope, whereas F1sc-->H-2b chimeras responded to the H-2b but not the H-2d restricted epitope. This pattern of epitope recognition by the sc chimeras indicated that APCs of recipient (scid) origin were involved in initiation of CTL responses. Significantly, CTL responses against epitopes presented by the mismatched donor class I molecules were elicited if F1 bone marrow cells and sc were transferred into scid recipients before or several days to weeks after DNA immunization. Thus, bone marrow-derived APCs are sufficient for class I MHC presentation of viral antigens after i.m. immunization with plasmid DNA. Expression of plasmid DNA by these APCs is probably not a requirement for CTL priming. Instead, they appear to present proteins synthesized by other host cells.
The role of vulnerability in stress‐related insomnia, social support and coping styles on incidence and persistence of insomnia

Individuals who are more prone to experience situational insomnia under stressful conditions may also be at greater risk to develop subsequent insomnia. While cross‐sectional data exist on the link between sleep reactivity (heightened vulnerability to stress‐related insomnia) and insomnia, limited data exist on its predictive value. The aim of the study was to evaluate prospectively whether sleep reactivity was associated with increased risk of incident and persistent insomnia in a population‐based sample of good sleepers. Social support and coping styles were also investigated as potential moderators. Participants were 1449 adults (Mage = 47.4 years, standard deviation = 15.1; 41.2% male) without insomnia at baseline and evaluated four times over 3 years. Sleep reactivity was measured using the Ford Insomnia Response to Stress Test (FIRST). Additional measures included depressive symptoms, the frequency and perceived impact of stressful life events, social support and coping styles. After controlling for prior sleep history, depressive symptoms, arousal predisposition, stressful life events and perceived impact, individuals with higher sleep reactivity had an odds ratio (OR) of 1.56 [95% confidence interval (CI): 1.13–2.16], 1.41 (95% CI: 0.87–2.30) and 2.02 (95% CI: 1.30–3.15) of developing insomnia symptoms, syndrome and persistent insomnia, respectively. Social support and coping styles did not moderate these associations. Results suggest that heightened vulnerability to insomnia is associated with an increased risk of developing new‐onset subsyndromal and persistent insomnia in good sleepers. Knowledge of premorbid differences is important to identify at‐risk individuals, as this may help to develop more targeted prevention and intervention strategies for insomnia.
Distinct habitat types arise along a continuous hydrodynamic stress gradient due to interplay of competition and facilitation

Though species interactions across local environmental gradients are well studied, the way in which species interactions shift between different habitats on a landscape scale has received less attention. We hypothesised that interactions among a suite of shoreline plant species shift across a hydrodynamic-exposure gradient, leading to generation of apparently distinct habitat types (e.g. bare cobble beaches, vegetated cobble beaches, fringing marshes and salt marshes). We examined hydrodynamic forcing and found that it was strongly correlated with shoreline habitat type. A trans- plant experiment revealed that all plants were rapidly crushed and abraded in bare cobble areas with high hydrodynamic energy and were out-competed by grasses in the low-energy salt marshes. Vegetated cobble beaches are inhabited by the largest amount of plant species under intermediate conditions, where hydrodynamic energy is sufficiently low to allow the establishment of the ecosys- tem engineer Spartina and sufficiently high to prevent the monopolisation of space by competitively dominant, but stress intolerant grasses. Experimentally reducing physical and biotic stresses (hydro- dynamics and interspecific competition) on bare cobble beaches and salt marshes, respectively, enabled forbs to persist across the whole gradient. These results demonstrate that the outcome of interspecific interactions at landscape scales is driven by background physical conditions, and that this can result in the development of what are considered distinct habitats.
The effects of a pedometer-based intervention on first-year university students: A randomized control trial

ABSTRACT Objectives: To assess the effects of a 12-week pedometer-based intervention on the physical activity behavior, health-related quality of life (HRQOL), and psychological well-being of first-year university students. Participants: First-year university students (N = 184) were recruited during September 2012 and randomly assigned to an intervention or a control group. Methods: Intervention participants were provided with a pedometer, monthly tracking logs, and follow-up e-mails. Control participants received no intervention. Physical activity, HRQOL, and psychological well-being were measured at baseline and post intervention. Data were analyzed using multivariate/univariate analysis of variance (MANOVA/ANOVA). Results: All participants experienced an increase in mild physical activity (p < .01) from baseline to follow-up. The intervention failed to produce significant differences between groups for physical activity (p = .28), HRQOL (p = .80), or psychological well-being (p = .72). Psychological well-being (p < .001), vigorous physical activity (p = .04), and mental health status (p < .001) decreased across the duration of the study. Conclusions: More intensive interventions may be required to elicit physical activity behavior change.
Thyroid Storm During Pregnancy

Thyroid storm is the major risk to pregnant women with thyrotoxicosis. This life-threatening condition is more likely to occur with another precipitating factor such as labor and delivery, surgical delivery, infection, or trauma. Thyroid storm most often occurs in patients with undertreated or undiagnosed hyperthyroidism. As many as 20% to 30% of cases can end in maternal and fetal mortality. Therefore, critical care nurses must be able to recognize and initiate proper medical and nursing interventions promptly.
Randomized controlled trial to improve primary care to prevent and manage childhood obesity: the High Five for Kids study.

OBJECTIVE To examine the effectiveness of a primary care-based obesity intervention over the first year (6 intervention contacts) of a planned 2-year study. DESIGN Cluster randomized controlled trial. SETTING Ten pediatric practices, 5 intervention and 5 usual care. PARTICIPANTS Four hundred seventy-five children aged 2 to 6 years with body mass index (BMI) in the 95th percentile or higher or 85th to less than 95th percentile if at least 1 parent was overweight; 445 (93%) had 1-year outcomes. INTERVENTION Intervention practices received primary care restructuring, and families received motivational interviewing by clinicians and educational modules targeting television viewing and fast food and sugar-sweetened beverage intake. OUTCOME MEASURES Change in BMI and obesity-related behaviors from baseline to 1 year. RESULTS Compared with usual care, intervention participants had a smaller, nonsignificant change in BMI (-0.21; 95% confidence interval [CI], -0.50 to 0.07; P = .15), greater decreases in television viewing (-0.36 h/d; 95% CI, -0.64 to -0.09; P = .01), and slightly greater decreases in fast food (-0.16 serving/wk; 95% CI, -0.33 to 0.01; P = .07) and sugar-sweetened beverage (-0.22 serving/d; 95% CI, -0.52 to 0.08; P = .15) intake. In post hoc analyses, we observed significant effects on BMI among girls (-0.38; 95% CI, -0.73 to -0.03; P = .03) but not boys (0.04; 95% CI, -0.55 to 0.63; P = .89) and among participants in households with annual incomes of $50 000 or less (-0.93; 95% CI, -1.60 to -0.25; P = .01) but not in higher-income households (0.02; 95% CI, -0.30 to 0.33; P = .92). CONCLUSION After 1 year, the High Five for Kids intervention was effective in reducing television viewing but did not significantly reduce BMI.
Iron overload in Africa. Interaction between a gene and dietary iron content.

BACKGROUND AND METHODS In contrast to hemochromatosis, which in white populations is inherited through a gene linked to the HLA locus, iron overload in sub-Saharan Africa is believed to result solely from increased dietary iron derived from traditional home-brewed beer. To examine the hypothesis that African iron overload also involves a genetic factor, we used likelihood analysis to test for an interaction between a gene (the hypothesized iron-loading locus) and an environmental factor (increased dietary iron) that determines transferrin saturation and unsaturated iron-binding capacity. We studied 236 members of 36 African families chosen because they contained index subjects with iron overload. Linkage to the HLA region was tested with use of lod scores. RESULTS In the index subjects, increased iron was present in both hepatocytes and cells of the mononuclear-phagocyte system. Among family members with increased dietary iron due to the consumption of traditional beer, transferrin saturation in serum was distributed bimodally, with 56 normal values (less than 60 percent saturation) and 44 elevated values; the mean serum ferritin concentration was five times higher in the subjects with elevated transferrin saturation (P less than 0.005). The pedigree analysis provided evidence of both a genetic effect (P less than 0.005) and an effect of increased dietary iron (P less than 0.005) on transferrin saturation and unsaturated iron-binding capacity. In the most likely model, increased dietary iron raised the mean transferrin saturation from 30 to 81 percent and lowered the mean unsaturated iron-binding capacity from 38 to 13 mumol per liter in subjects heterozygous for the iron-loading locus. The hypothesis of tight linkage to HLA was rejected. CONCLUSIONS Iron overload in Africa may be caused by an interaction between the amount of dietary iron and a gene distinct from any HLA-linked gene.
Interaction of Cryptosporidium hominis and Cryptosporidium parvum with Primary Human and Bovine Intestinal Cells

ABSTRACT Cryptosporidiosis in humans is caused by the zoonotic pathogen Cryptosporidium parvum and the anthroponotic pathogen Cryptosporidium hominis. To what extent the recently recognized C. hominis species differs from C. parvum is unknown. In this study we compared the mechanisms of C. parvum and C. hominis invasion using a primary cell model of infection. Cultured primary bovine and human epithelial intestinal cells were infected with C. parvum or C. hominis. The effects of the carbohydrate lectin galactose-N-acetylgalactosamine (Gal/GalNAc) and inhibitors of cytoskeletal function and signal transduction mechanisms on entry of the parasites into host cells were tested. HCT-8 cells (human ileocecal adenocarcinoma cells) were used for the purpose of comparison. Pretreatment of parasites with Gal/GalNAc inhibited entry of C. parvum into HCT-8 cells and primary bovine cells but had no effect on entry of either C. parvum or C. hominis into primary human cells or on entry of C. hominis into HCT-8 cells. Both Cryptosporidium species entered primary cells by a protein kinase C (PKC)- and actin-dependent mechanism. Staurosporine, in particular, attenuated infection, likely through a combination of PKC inhibition and induction of apoptosis. Diversity in the mechanisms used by Cryptosporidium species to infect cells of different origins has important implications for understanding the relevance of in vitro studies of Cryptosporidium pathogenesis.
Interferon-γ Listericidal Action Is Mediated by Novel Rab5a Functions at the Phagosomal Environment*

Control and clearance of Listeria monocytogenes infection is an interferon-γ-dependent process. The listericidal mechanism of action involves activation of NADPH oxidase and inducible nitric-oxide synthase to produce reactive oxygen and nitrogen intermediate radicals, respectively. Recently, we have described in a nonpathogenic model of L. monocytogenes (hemolysin negative mutant strain) that the interferon-γ-inducible GTPase Rab5a contributed to Listeria destruction in resting macrophages. Here, we report in a pathogenic model of L. monocytogenes(hemolysin-positive strain) that Rab5a plays a central role inListeria destruction induced by interferon-γ and within the phagosomal environment. These findings reveal the importance of Rab5a as the responsible factor mediating the listericidal action of interferon-γ. Active Rab5a causes remodeling of the phagosomal environment, facilitates the translocation of Rac2 to LM phagosomes, and regulates the activity of this GTPase. Rac2 activation and translocation governs the phagocyte NADPH oxidase activity and the consequent reactive oxygen intermediate production that leads to killing of the pathogen.
Focal cemento-osseous dysplasia involving a mandibular lateral incisor.

AIM To report a case of focal cemento-osseous dysplasia (FCOD) affecting a single tooth misdiagnosed as an inflammatory periapical lesion. SUMMARY The patient, a black 47-year-old woman complained of pain affecting the right side of the mandible. Routine X-ray examination discovered a periapical radiolucency on the mandibular left lateral incisor (tooth 32), which was otherwise normal and not carious. As the response of this tooth to a vitality test was doubtful, the lesion was diagnosed as a periapical granuloma or cyst secondary to pulpal necrosis. Endodontic treatment and curettage of the periapical lesion were performed, and histological examination of the curettage material revealed a localized osseous dysplasia. KEY LEARNING POINTS FCOD may rarely affect only one tooth, resembling a periapical granuloma or cyst. Careful diagnosis is of paramount importance in cases of questionable periapical lesions affecting normal-looking teeth, before beginning treatment. FCOD generally requires no treatment. Biopsy is warranted in case of doubt.
Technique for Accurate Power and Energy Measurement with the Computer-Aided Design Tools

Computer-aided design (CAD) tools are frequently employed to verify the design objectives before the fabrication of an integrated circuit. An important circuit parameter that requires accurate characterization is the power consumption due to the strict constraints on the acceptable power envelope of integrated systems. Circuit simulators typically provide built-in functions to measure the power consumption. However, the accuracy of the measured power is mostly overlooked since the approximations and the methodologies used by the existing built-in power estimation tools are not well documented. The research community tends to assume that the built-in functions provide accurate power figures. This blind-trust in the CAD tools, however, may lead to gross errors in power estimation. A generic methodology to accurately measure the power and energy consumption with the circuit simulators is described in this paper. An equation to calculate the device power consumption based on the different current conduction paths in a MOSFET is presented. An expression for the total power consumption of a complex circuit is derived by explicitly considering the different circuit terminals including the inputs, the outputs, and the body-contacts. Results indicate that the power measurements with the built-in functions of widely used commercial circuit simulators can introduce significant errors in a 65 nm CMOS technology. For deeply scaled nano-CMOS circuits, a conscious power and energy measurement with the proposed explicit methodology is recommended for an accurate pre-fabrication circuit characterization.
Small-signal analysis of DC-DC converters with sliding mode control

The paper deals with small-signal analysis of DC-DC power converters with sliding mode control. A suitable small-signal model is developed, which allows selection of control coefficients, analysis of parameter variation effects and characterization of the closed-loop behavior in terms of audiosusceptibility, output and input impedances and reference-to-output transfer function. Unlike previous analyses, the model includes effects of the filters used to evaluate state variable errors. Simulated and experimental results demonstrate model potentialities. <<ETX>>
Strategies for increasing the operating frequency range of vibration energy harvesters: a review

This review presents possible strategies to increase the operational frequency range of vibration-based micro-generators. Most vibration-based micro-generators are spring-mass-damper systems which generate maximum power when the resonant frequency of the generator matches the frequency of the ambient vibration. Any difference between these two frequencies can result in a significant decrease in generated power. This is a fundamental limitation of resonant vibration generators which restricts their capability in real applications. Possible solutions include the periodic tuning of the resonant frequency of the generator so that it matches the frequency of the ambient vibration at all times or widening the bandwidth of the generator. Periodic tuning can be achieved using mechanical or electrical methods. Bandwidth widening can be achieved using a generator array, a mechanical stopper, nonlinear (e.g. magnetic) springs or bi-stable structures. Tuning methods can be classified into intermittent tuning (power is consumed periodically to tune the device) and continuous tuning (the tuning mechanism is continuously powered). This review presents a comprehensive review of the principles and operating strategies for increasing the operating frequency range of vibration-based micro-generators presented in the literature to date. The advantages and disadvantages of each strategy are evaluated and conclusions are drawn regarding the relevant merits of each approach.
Maximizing the profit of a load aggregator by optimal scheduling of day ahead load with EVs

This paper proposes optimal scheduling of imported power of a load aggregator (LA) with the utilization of electric vehicles (EVs) to maximize its profit. As with the increase of renewable energy resources, electricity price in competitive market becomes more uncertain and on the other hand with the penetration of renewable distributed generators in the distribution network the predicted load of an LA also becomes uncertain in real time. Though there is uncertainties in both load and price but the use of EVs storage capacity can make the operation of load aggregator flexible. LA submits its offer to day-ahead market based on predicted loads and optimized use of its EVs to maximize its profit as well as in real time operation it uses its energy storage capacity such as way that it can maximize its profit. In this project load aggregators profit maximization algorithm is formulated and the optimization problem is solved with the help of a MATLA based optimization tool CVX (convex). As in real time operation the forecasted loads differ from actual load, the mismatches are settled in real time balancing market. Simulation results compare the profit of an LA with a hypothetical group of 1000 EVs and without EVs.