Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of a PY motif in the epithelial Na channel subunits as a target sequence for mutations causing channel activation found in Liddle syndrome.

Liddle syndrome is an autosomal dominant form of hypertension, resulting from mutations in the cytoplasmic C‐terminus of either the beta or gamma subunits of the amiloride‐sensitive epithelial Na channel (ENaC) which lead to constitutively increased channel activity. Most mutations reported to date result in the elimination of 45–75 normal amino acids from these segments, leaving open the question of the identity of the precise amino acids in which mutation can lead to an enhanced channel activity. To address this question, we have performed a systematic mutagenesis study of the C‐termini of the alpha, beta and gamma ENaC subunits of the rat channel and have analyzed their function by expression in Xenopus oocytes. The results demonstrate that a short proline‐rich segment present in the cytoplasmic C‐terminus of each subunit is required for the normal regulation of channel activity. Missense mutations altering a consensus PPPXY sequence of the alpha, beta or gamma subunits reproduced the increase in channel activity found in mutants in which the entire cytoplasmic C‐termini are deleted. This proline‐rich sequence, referred to as the PY motif, is known to be a site of binding by proteins bearing a WW domain. These findings show that the three PY motifs in the C‐termini of ENaC are involved in the regulation of channel activity, probably via protein‐protein interactions. This new regulatory mechanism of channel function is critical for the maintenance of normal Na reabsorption in the kidney and of Na+ balance and blood pressure.
A study on improving security warnings

Security warnings are intended to alert users about the possibility of events that may compromise their protection. They encounter security warnings on daily basis in many situations when dealing with their computer. However, prior studies have shown that users often have difficulty in understanding the warnings, which can pose a particular risk in cases where they are required to make a decision. Well gathered information is needed to help the researchers and other people to further understand this area. This paper describes an overview of studies on security warnings. It covers problems that end users encounter with security warnings, possible solutions and approaches of security warnings and useful classification of security warnings studies. It is expected that this paper will benefit the research community or general public to understand the problems and possible solutions in improving security warnings.
The proinflammatory cytokine response following resuscitation in the swine model depends on the method of ventricular fibrillation induction.

OBJECTIVES A systemic inflammatory response has been reported following resuscitation from cardiac arrest. The purpose of this study was to compare the magnitude of the tumor necrosis factor-alpha (TNF-alpha) response in two different swine models of ventricular fibrillation (VF) arrest. METHODS This was a randomized comparative trial conducted with domestic swine (N = 28, mean weight 40 kg, range 34-49 kg) of both genders. Anesthetized and instrumented swine were randomized to electrically induced VF (n = 14) or spontaneous VF induced by occlusion of a coronary artery (n = 14). After 8 minutes of VF, countershocks were given and standard advanced cardiac life support was initiated. Resuscitated animals were observed for 3 hours, and hemodynamics, base excess, and TNF-alpha concentrations were measured at intervals. RESULTS TNF-alpha concentrations were significantly greater in the ischemic VF group throughout the postresuscitation period. Multivariate modeling demonstrated that the TNF-alpha level was dependent on the method of VF induction and correlated with ischemia time (untreated VF period plus time to restoration of circulation) and the degree of postresuscitation hypoperfusion as reflected in base excess measurements. CONCLUSIONS This study demonstrates that TNF-alpha concentrations increase after resuscitation from cardiac arrest and that the TNF-alpha response is more profound in animals subjected to ischemic, spontaneous VF. The observed differences may be due to a longer resuscitation time and persistent postresuscitation hypoperfusion in the ischemic VF group. These differences need to be considered in studies evaluating mechanisms of postresuscitation organ dysfunction and defining mortality markers.
STAT3 activation in photoreceptors by leukemia inhibitory factor is associated with protection from light damage

Members of the interleukin‐6 cytokine family, including leukemia inhibitory factor (LIF), signal through gp130. The neuroprotective role of gp130 activation has been widely demonstrated in both CNS and PNS, but the mechanism by which this is accomplished is not well established. We investigated temporal and cell‐specific activation of signaling pathways induced by LIF in the mature mouse retina. Intravitreal injection of LIF preserved photoreceptor function and prevented photoreceptor cell death from light‐induced oxidative damage in a dose‐dependent manner (2 days post‐injection). A therapeutic dose of LIF induced rapid and sustained activation of signal transducer and activator of transcription (STAT) 3. Activated STAT3 was localized to all the retinal neurons and glial cells, including photoreceptors. Activation of extracellular signal‐regulated kinase 1 and 2 was robust but transient in Müller glial cells, and undetectable at the time of light exposure. Akt was not activated by LIF. We also show that at the time of neuroprotection, STAT3 but not extracellular signal‐regulated kinase 1 and 2 or the Akt pathways was active in LIF‐treated retinas, and activated STAT3 was clearly localized in transcriptionally active areas of photoreceptor nuclei. Our data suggest that photoreceptor protection in response to LIF can be directly mediated by activation of STAT3 in photoreceptors.
Adaptive saturation scheme to limit the capacity of a shunt active power filter

When the current reference of a shunt active power filter (SAPF) changes quicker than the output current can change, the output of the APF cannot precisely track the current reference. Undesired harmonics will be generated by the APF due to the controller saturation. Based on detailed analysis of the reason and consequences of the controller saturation problem, this paper proposes an adaptive saturation scheme to suppress the effect of saturation by using the feedback of the current error signal. The proposed scheme can adaptively adjust the capacity of the APF according to different load conditions. The adjusted reference is still in phase with the original calculated harmonics and contains no extra undesired harmonics. Also, this algorithm has no risk of affecting the reference when there is no saturation. Simulation results show that the proposed scheme can operate effectively and the effect of saturation is greatly reduced
Photon assisted ultra-selective Formaldehyde sensing by defect induced NiO nanostructured sensing layer

Indoor air quality (IAQ) monitoring is quite essential to maintain healthy human life. Among different pollutants effecting IAQ, formaldehyde is one toxic VOC that needs to be monitored. In this work, hierarchical NiO nanostructured thin film devices are used as highly selective and sensitive formaldehyde sensor in presence of light. The response in presence of light was obtained as 291.7% at 190 ppm with a fast response time of ∼ 24 s and recovery time of ∼ 42 s (at 190 ppm of formaldehyde). The sensor was found to be highly specific towards formaldehyde compared to other VOCs. The optimum operating temperature was ∼ 300°C, much less than the conventional NiO based sensors (∼600°C). The sensing layer was made optically active by inducing defects which resulted in the dependence of the sensing response on light irradiation to a considerable amount (∼82.4% in dark and ∼291.7% in light for 190 ppm formaldehyde). Thus, the fabricated light assisted sensor shows potential to develop future commercial formaldehyde sensor.
Complexity of Strong Satisfiability Problems for Reactive System Specifications

Many fatal accidents involving safety-critical reactive systems have occurred in unexpected situations, which were not considered during the design and test phases of system development. To prevent such accidents, reactive systems should be designed to respond appropriately to any request from an environment at any time. Verifying this property during the specification phase reduces the development costs of safety-critical reactive systems. This property of a specification is commonly known as realizability. The complexity of the realizability problem is 2EXPTIMEcomplete. We have introduced the concept of strong satisfiability, which is a necessary condition for realizability. Many practical unrealizable specifications are also strongly unsatisfiable. In this paper, we show that the complexity of the strong satisfiability problem is EXPSPACE-complete. This means that strong satisfiability offers the advantage of lower complexity for analysis, compared to realizability. Moreover, we show that the strong satisfiability problem remains EXPSPACE-complete even when only formulae with a temporal depth of at most 2 are allowed. key words: reactive system, strong satisfiability, realizability, complexity, LTL specification
Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer.

PURPOSE Both gemcitabine (GEM) and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This open-label study was designed to compare the overall survival (OS) of patients randomly assigned to GEM alone or GEM plus capecitabine (GEM-CAP). PATIENTS AND METHODS Patients with previously untreated histologically or cytologically proven locally advanced or metastatic carcinoma of the pancreas with a performance status <or= 2 were recruited. Patients were randomly assigned to GEM or GEM-CAP. The primary outcome measure was survival. Meta-analysis of published studies was also conducted. RESULTS Between May 2002 and January 2005, 533 patients were randomly assigned to GEM (n = 266) and GEM-CAP (n = 267) arms. GEM-CAP significantly improved objective response rate (19.1% v 12.4%; P = .034) and progression-free survival (hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .004) and was associated with a trend toward improved OS (HR, 0.86; 95% CI, 0.72 to 1.02; P = .08) compared with GEM alone. This trend for OS benefit for GEM-CAP was consistent across different prognostic subgroups according to baseline stratification factors (stage and performance status) and remained after adjusting for these stratification factors (P = .077). Moreover, the meta-analysis of two additional studies involving 935 patients showed a significant survival benefit in favor of GEM-CAP (HR, 0.86; 95% CI, 0.75 to 0.98; P = .02) with no intertrial heterogeneity. CONCLUSION On the basis of our trial and the meta-analysis, GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer.
La regulación contable sobre divulgación de riesgos en los estados financieros

Una de las principales debilidades que se le atribuyen al modelo contable actual es la carencia de informacion sobre los riesgos a que estan expuestas las empresas. Este analisis nos permitira constatar que la regulacion existente se limita a los riesgos de los instrumentos financieros, mientras que la reforma contable representa una excelente oportunidad para incluir la obligatoriedad de presentar informacion sobre el perfil de riesgo de la organizacion que permita, ademas, su compararabilidad
Artemin improves survival of spiral ganglion neurons in vivo and in vitro

Artemin and its receptors are upregulated in the auditory nerve of deafened rats as a possible intrinsic protective mechanism against ototoxicity-related apoptosis. Consequently, we examined the effect of artemin on spiral ganglion neurons in vitro and in vivo. Spiral ganglion neurons were isolated from neonatal rats and cultured in serum-free medium supplemented with artemin and/or brain-derived neurotrophic factor (BDNF). In vitro, the survival rate of spiral ganglion neurons cultivated with artemin or BDNF was significantly improved compared with negative controls. In addition, artemin was delivered to the inner ear of deafened guinea pigs for 28 days. In-vivo artemin was as effective as BDNF in spiral ganglion neuron protection. Therefore, artemin promotes the survival of spiral ganglion neurons in vitro and in vivo.
On the role of coupling factor B in the mitochondrial Pi-ATP exchange reaction.

Bovine heart mitochondrial coupling factor B (Factor B) has been prepared by a modification of the procedure of Lam et al. (Lam, K. W., Warshaw, J. B., and Sanadi, D. R. (1967) Arch. Biochem. Biophys. 119,477484). It has the highest specific activity (over 100 pmol of NAD reduced x min-’ x mg-’ of protein) compared to any related preparation. Its molecular weight under both denaturing and native conditions was approximately 13,000. It appeared as a single component in polyacrylamide gel electrophoresis both in the presence and absence of dodecyl sulfate. Rabbit anti-Factor B serum gave a single line in immunoelectrophoresis against partially as well as highly purified Factor B. A preparation of energy-transducing ATPase complex which is partially deficient in Factor B has been isolated from particles @E-particles) derived by ammonia-EDTA extraction of heart mitochondria. The hydrophobic membrane protein fraction (AE-Fo) derived from it by treatment with sodium bromide, recombines with mitochondrial coupling factor 1 (R) with the restoration of oligomycin-sensitive ATPase activity. The Pi-ATP exchange activity of this AE-Fo + F1 is minimal and is stimulated over lo-fold upon addition of Factor B. Complete elimination of exchange activity of AE-Fo + F1 was achieved by prior treatment of AE-Fo with Nethylmaleimide, although ATPase activity was retained with unaltered sensitivity to oligomycin. Addition of Factor B to this AE-F. + F1 led to restoration of Pi-ATP exchange activity and to partial inhibition of ATPase activity. The presence of Factor B in the ATPase complex and derivative fractions was determined by Ouchterlony double diffusion experiments. Antigen in the ATPase complex was not detectable after the ATPase had been washed with ammonia/EDTA; concomitantly, the stimulation of exchange activity by Factor B increased to over B-fold. These results show that PiATP exchange activity has an absolute requirement for Factor B, but binding of F1 to AE-Fo, and oligomycin sensitivity of the resulting ATPase, are independent of the factor.
Debt, Deficits and Destabilizing Monetary Policy in Open Economies

Blanchard (2005) suggested that active interest rate policy might induce unstable dynamics in highly-indebted economies. We examine this in a dynamic general equilibrium model where Calvo-type price rigidities provide a rationale for inflation stabilization. Unstable dynamics can occur when the CB is aggressively raising the interest rate in response to higher expected inflation. The constraint on stabilizing interest rate policy is tighter the higher the primary deficit and the more open the economy is. If the government cannot borrow from abroad in its own currency, stability requires interest rate policy to be accommodating (passive). Inflation stabilization is nevertheless feasible if the CB uses an instrument not associated with default risk, e.g. money supply.
Reduced description of reactive flows with tabulation of chemistry

The direct use of large chemical mechanisms in multi-dimensional Computational Fluid Dynamics (CFD) is computationally expensive due to the large number of chemical species and the wide range of chemical time scales involved. To meet this challenge, a reduced description of reactive flows in combination with chemistry tabulation is proposed to effectively reduce the computational cost. In the reduced description, the species are partitioned into represented species and unrepresented species; the reactive system is described in terms of a smaller number of represented species instead of the full set of chemical species in the mechanism; and the evolution equations are solved only for the represented species. When required, the unrepresented species are reconstructed assuming that they are in constrained chemical equilibrium. In situ adaptive tabulation (ISAT) is employed to speed the chemistry calculation through tabulating information of the reduced system. The proposed dimension-reduction / tabulation methodology determines and tabulates in situ the necessary information of the nr-dimensional reduced system based on the ns-species detailed mechanism. Compared to the full description with ISAT, the reduced descriptions achieve additional computational speed-up by solving fewer transport equations and faster ISAT retrieving. The approach is validated in both a methane/air premixed flame and a methane/air non-premixed flame. With the GRI 1.2 mechanism consisting of 31 species, the reduced descriptions (with 12 to 16 represented species) achieve a speed-up factor of up to three compared to the full description with ISAT, with a relatively moderate decrease in accuracy compared to the full description.
Motivational interviewing for adherence problems in cystic fibrosis

This review focuses on adherence in cystic fibrosis (CF), and the factors known to influence it. In particular, it discusses the importance of effective communication in clinical settings and considers the evidence for the effectiveness of motivational interviewing (MI), to increase adaptation and adherence in physical health and CF. The review also contains an overview of the key concepts of MI, its' practice in medical settings and recommendations on how to adopt MI techniques in the routine care of people with CF. Pediatr Pulmonol. 2010; 45:211–220. © 2010 Wiley‐Liss, Inc.
An Agonist of Toll-Like Receptor 5 Has Radioprotective Activity in Mouse and Primate Models

The toxicity of ionizing radiation is associated with massive apoptosis in radiosensitive organs. Here, we investigate whether a drug that activates a signaling mechanism used by tumor cells to suppress apoptosis can protect healthy cells from the harmful effects of radiation. We studied CBLB502, a polypeptide drug derived from Salmonella flagellin that binds to Toll-like receptor 5 (TLR5) and activates nuclear factor–κB signaling. A single injection of CBLB502 before lethal total-body irradiation protected mice from both gastrointestinal and hematopoietic acute radiation syndromes and resulted in improved survival. CBLB502 injected after irradiation also enhanced survival, but at lower radiation doses. It is noteworthy that the drug did not decrease tumor radiosensitivity in mouse models. CBLB502 also showed radioprotective activity in lethally irradiated rhesus monkeys. Thus, TLR5 agonists could potentially improve the therapeutic index of cancer radiotherapy and serve as biological protectants in radiation emergencies.
Absolute Optical Frequency Measurement of the Cesium D 1 Line with a Mode-Locked Laser

We have measured the absolute optical frequency of the cesium ${D}_{1}$ line at 335 THz (895 nm). This frequency provides an important link for a new determination of the fine structure constant $\ensuremath{\alpha}$. The ${D}_{1}$ line has been compared with the fourth harmonic of a methane stabilized He-Ne laser at 88.4 THz ( $3.39\ensuremath{\mu}\mathrm{m}$). To measure the frequency mismatch of 18.39 THz between $4\ifmmode\times\else\texttimes\fi{}88.4\mathrm{THz}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}354\mathrm{THz}$ and the ${D}_{1}$ line a frequency comb spanning around 244 000 modes of a Kerr-lens mode-locked laser was used. We find 1 167 688 (81) kHz for the hyperfine splitting of the ${6P}_{1/2}$ state and 335 116 048 807 (41) kHz for the hyperfine centroid from which we derive ${\ensuremath{\alpha}}^{\ensuremath{-}1}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}137.0359924(41)$.
The relationship of slicing and debugging to program understanding

The paper describes a study that explores the relationship between program slicing and code understanding gained while debugging. The study consisted of an experiment that compared the program understanding abilities of two classes of debuggers: those who slice while debugging and those who do not. For debugging purposes, a slice can be thought of as a minimal subprogram of the original code that contains the program faults. Those who only examine statements within a slice for correctness are considered slicers; all others are considered non-slicers. Using accuracy of reconstruction as a measure of understanding, it was determined that slicers have a better understanding of the code after debugging.
Travel Time and Attrition From VHA Care Among Women Veterans: How Far is Too Far?

Background:Travel time, an access barrier, may contribute to attrition of women veterans from Veterans Health Administration (VHA) care. Objective:We examined whether travel time influences attrition: (a) among women veterans overall, (b) among new versus established patients, and (c) among rural versus urban patients. Research Design:This retrospective cohort study used logistic regression to estimate the association between drive time and attrition, overall and for new/established and rural/urban patients. Subjects:In total, 266,301 women veteran VHA outpatients in the Fiscal year 2009. Measures:An “attriter” did not return for VHA care during the second through third years after her first 2009 visit (T0). Drive time (log minutes) was between the patient’s residence and her regular source of VHA care. “New” patients had no VHA visits within 3 years before T0. Models included age, service-connected disability, health status, and utilization as covariates. Results:Overall, longer drive times were associated with higher odds of attrition: drive time adjusted odds ratio=1.11 (99% confidence interval, 1.09–1.14). The relationship between drive time and attrition was stronger among new patients but was not modified by rurality. Conclusions:Attrition among women veterans is sensitive to longer drive time. Linking new patients to VHA services designed to reduce distance barriers (telemedicine, community-based clinics, mobile clinics) may reduce attrition among women new to VHA.
In-Vehicle Information Systems to Meet the Needs of Drivers

In-Vehicle Information Systems (IVISs) integrate most of the secondary functions available within vehicles. These secondary functions are aimed at enhancing the driving experience. To successfully design and evaluate the performance of these systems, a thorough understanding of the task, user, and system is required. This article presents a review of these three variables in the context of IVISs, which aims to enhance understanding of this specific task–user–system interaction. A framework for modeling system performance for the task–user–system interaction is also proposed. This will allow designers and evaluators of IVISs to make predictions about system performance and to design systems that meet a set of criteria for usable IVISs.