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Hereditary fibrosing poikiloderma (HFP) is a rare human dominant negative disorder caused by mutations in the FAM111B gene that encodes a nuclear trypsin-like serine protease. HFP patients present with symptoms including skin abnormalities, tendon contractures, myopathy and lung fibrosis. We characterized the cellular roles of human FAM111B using U2OS and MCF7 cell lines and report here that the protease interacts with components of the nuclear pore complex. Loss of FAM111B expression resulted in abnormal nuclear shape and reduced telomeric DNA content suggesting that FAM111B protease is required for normal telomere length; we show that this function is independent of telomerase or recombination driven telomere extension. Even though FAM111B-deficient cells were proficient in DNA repair, they showed hallmarks of genomic instability such as increased levels of micronuclei and ultra-fine DNA bridges. When mutated as in HFP, FAM111B was more frequently localized to the nuclear envelope, suggesting that accumulation of the mutated protease at the nuclear periphery may drive the disease pathology.

Fluorides and their CO 2 mixtures are considered as promising choices of SF 6 -substitute gases due to their low global warming potentials and high dielectric strength. This paper investigates physical and chemical properties and breakdown characteristics of different common fluorides and their mixtures for application in the power system. For dielectric characteristics of fluorides and their mixtures, their power frequency breakdown voltages are determined experimentally, and the results are compared with SF 6 . For physical and chemical characteristics, the saturated vapor pressures, global warming potentials (GWPs), toxicities, prices of fluorides and their mixtures are calculated, and the corresponding characteristic curves are obtained. Based on characteristics mentioned above, a method for obtaining the optimal gas parameters of a specific fluoride mixture is proposed, which can be used as a feasible solution to find an SF 6 alternative gas that meets the application requirements. The results show that CO 2 mixtures with hexafluoropropene (HFP), 1,1,1,2-tetrafluoroethane (HFC-134a) and perfluoroisobutyronitrile (C4-PFN) are three types of good SF 6 -substitute gases. HFP/CO 2 mixtures with HFP component ratios 0.32 to 0.6 are suitable for applications at 0.1 to 0.3 MPa. HFC-134a/CO 2 mixtures (HFC-134a component ratios from 0.16 to 0.2) are suitable for applications at 0.3 to 0.5 MPa. C4-PFN/CO 2 mixtures (C4-PFN component ratios from 0.09 to 0.12) could be used for the applications at 0.1 to 0.5 MPa, regardless of the gas price. [ABSTRACT FROM AUTHOR]

El manglar es un ecosistema complejo y dinámico, considerado un humedal de importancia internacional ya que posee una fuerte interrelación inter/intra específica con el medio. Su importancia radica en innumerables servicios que brindan a distintos ámbitos, incluyendo el económico. Sin embargo, pese a esto, los manglares han sido impactados negativamente por la contaminación, teniendo una tasa anual de deforestación de aproximadamente 2.5%, pasando de 775 mil ha en 2005 a 764 mil 486 ha en 2010. El objetivo de esta investigación fue establecer dos zonas del sitio Ramsar 1602 “Manglares y Humedales de Tuxpan”, una al norte y otra al sur (ZN y ZS), de una hectárea de superficie cada una. Dentro de los principales contaminantes del área se encuentran efectos del turismo, infraestructura carretera y petrolera, actividades agropecuarias y marícolas, la reducción del flujo de agua por obras de riego y contaminación de las aguas por agroquímicos, metales pesados, nutrimentos e hidrocarburos asociados a varias actividades, principalmente en la zona norte. Se evaluaron concentraciones de hidrocarburos fracción pesada (HFP) en 16 submuetras de los dos áreas obtenidas a una profundidad de 70 cm de la superficie para obtener una muestra compuesta por cada zona, la cual fue analizada (EPA 1661a y 9071b con algunas modificaciones), cuantificando los HFP por diferencia de peso. Se encontraron hidrocarburos fracción pesada en ambas zonas de muestreo, con la mayor concentración en la zona norte, sin embargo, las concentraciones no fueron estadísticamente diferentes.

In this study, particle swarm optimisation (PSO) is applied to determine the Heidler's function parameters (HFPs) for approximating the measured full lightning channel‐base‐current (CBC) of the severe (5% data in IEC standard 62305‐1, 2010) negative first return stroke (NFS) and subsequent return stroke (NSS). The parameters in the sum of two Heidler's functions, namely I01, I02, τ11, τ12, τ21, τ22, n1, and n2, are identified using PSO as a tool. The HFPs for severe NFS and NSS are tuned to keep four parameters constant with systematic variation of one out of all prominent parameters (i.e. peak current (Im), maximum time rate of change of current ((di/dt)max), front duration (tFD), stroke duration (tSD), and total charge (Q)) of full CBC wave and vice versa. The corresponding data is reported, and an independent controlling of HFPs is analysed to achieve the desired full CBC wave. Also, an attempt has been made in this study to examine the interdependence between the wavefront and tail of CBC using PSO. The data thus generated and reported for severe NFS and NSS can be used to generate the suitable full CBC waveforms. This methodology will be helpful in lightning‐related simulation study and research. [ABSTRACT FROM AUTHOR]

This paper continues a series of studies in which the Serpent 2 Monte Carlo code is used for producing homogenized group constants for the ARES core simulator. The test case is the MIT BEAVRS benchmark, which involves the detailed description of a 1000 MW Westinghouse PWR core and the operating data for the first two cycles. Previous initial core hot zero-power calculations are extended to full power conditions and fuel cycle simulation. The results of the Serpent-ARES code sequence are compared to a reference Serpent 3D calculation and experimental data provided with the benchmark specification. It is concluded that the results are in good agreement. This study also demonstrates that the Monte Carlo method can be a viable, albeit computationally expensive option for group constant generation, even if the procedure involves accounting for fuel burnup and covering the full range of reactor operating conditions. [ABSTRACT FROM AUTHOR]

In this research, the simulation of one-sixth of VVER-1000 (Bushehr) reactor core is carried out by WIMS-D4 nuclear code, based on symmetry of core and also by information obtained from FSAR. The cross sections of some nuclides are obtained by WIMS-D4 from the beginning of cycle (BOC) to the end of cycle (EOC), and they are transferred into the CITATION code as inputs. In the next stage, the amounts of neutron fluxes and power of reactor core are obtained by CITATION code in the CZP and HFP states. Then, the received products are returned again into the extended program cycle, thereby distributions of neutron fluxes and power are finally depicted. In the meantime, the space distribution of neutron fluxes and power throughout the core are presented during the normal operation by this simulation. It can be inferred that if the reactor operation continues, a flat power distribution will be made in the reactor core that might cause maximum power. [ABSTRACT FROM AUTHOR]

Abstract: Polyaniline (PANi), a conductive polymer, was blended with a natural protein, gelatin, and co-electrospun into nanofibers to investigate the potential application of such a blend as conductive scaffold for tissue engineering purposes. Electrospun PANi–contained gelatin fibers were characterized using scanning electron microscopy (SEM), electrical conductivity measurement, mechanical tensile testing, and differential scanning calorimetry (DSC). SEM analysis of the blend fibers containing less than 3% PANi in total weight, revealed uniform fibers with no evidence for phase segregation, as also confirmed by DSC. Our data indicate that with increasing the amount of PANi (from 0 to ∼5%w/w), the average fiber size was reduced from 803±121nm to 61±13nm () and the tensile modulus increased from 499±207MPa to 1384±105MPa (). The results of the DSC study further strengthen our notion that the doping of gelatin with a few % PANi leads to an alteration of the physicochemical properties of gelatin. To test the usefulness of PANi-gelatin blends as a fibrous matrix for supporting cell growth, H9c2 rat cardiac myoblast cells were cultured on fiber-coated glass cover slips. Cell cultures were evaluated in terms of cell proliferation and morphology. Our results indicate that all PANi-gelatin blend fibers supported H9c2 cell attachment and proliferation to a similar degree as the control tissue culture-treated plastic (TCP) and smooth glass substrates. Depending on the concentrations of PANi, the cells initially displayed different morphologies on the fibrous substrates, but after 1week all cultures reached confluence of similar densities and morphology. Taken together these results suggest that PANi-gelatin blend nanofibers might provide a novel conductive material well suited as biocompatible scaffolds for tissue engineering. [Copyright &y& Elsevier]

Abstract: Electrospinning has recently emerged as a leading technique for generating biomimetic scaffolds made of synthetic and natural polymers for tissue engineering applications. In this study, we compared collagen, gelatin (denatured collagen), solubilized alpha-elastin, and, as a first, recombinant human tropoelastin as biopolymeric materials for fabricating tissue engineered scaffolds by electrospinning. In extending previous studies, we optimized the shape and size (diameter or width) 1 [1] Diameter is used to describe the rounded gelatin and collagen fibers and width is used to describe the ribbon-like elastin and tropoelastin fibers. of the ensuing electrospun fibers by varying important parameters of the electrospinning process, such as solute concentration and delivery rate of the polymers. Our results indicate that the average diameter of gelatin and collagen fibers could be scaled down to 200–500nm without any beads, while the alpha-elastin and tropoelastin fibers were several microns in width. Importantly, and contrary to any hitherto reported structures of electrospun polymers, fibers composed of alpha-elastin, especially tropoelastin, exhibited “quasi-elastic” wave-like patterns at increased solution delivery rates. The periodicity of these wave-like tropoelastin fibers was partly affected by the delivery rate. Atomic force microscopy was utilized to profile the topography of individual electrospun fibers and microtensile testing was performed to measure their mechanical properties. Cell culture studies confirmed that the electrospun engineered protein scaffolds support attachment and growth of human embryonic palatal mesenchymal (HEPM) cells. [Copyright &y& Elsevier]

Mammalian FIR has dual roles in pre-mRNA splicing and in negative transcriptional control of Myc. Here we show that Half pint (Hfp), the Drosophila orthologue of FIR, inhibits cell proliferation in Drosophila. We find that Hfp overexpression potently inhibits G1/S progression, while hfp mutants display ectopic cell cycles. Hfp negatively regulates dmyc expression and function, as reducing the dose of hfp increases levels of dmyc mRNA and rescues defective oogenesis in dmyc hypomorphic flies. The G2delay in dmyc-overexpressing cells is suppressed by halving the dosage of hfp, indicating that Hfp is also rate-limiting for G2-M progression. Consistent with this, the cycle 14 G2-arrest of stg mutant embryos is rescued by the hfp mutant. Analysis of hfp mutant clones revealed elevated levels of Stg protein, but no change in the level of stg mRNA, suggesting that hfp negatively regulates Stg via a post-transcriptional mechanism. Finally, ectopic activation of the wingless pathway, which is known to negatively regulate dmyc expression in the wing, results in an accumulation of Hfp protein. Our findings indicate that Hfp provides a critical molecular link between the developmental patterning signals induced by the wingless pathway and dMyc-regulated cell growth and proliferation. [ABSTRACT FROM AUTHOR]

: ObjectivesThe aim of this study was to explore the value of noninvasive predictors of death/mode of death in ambulant outpatients with chronic heart failure (HF).: BackgroundMortality in chronic HF remains high, with a significant number of patients dying of progressive disease. Identification of these patients is important.: MethodsWe recruited 553 ambulant outpatients age 63 ± 10 years with symptoms of chronic HF (New York Heart Association functional class, 2.3 ± 0.5) and objective evidence of left ventricular dysfunction (ejection fraction <45%, cardiothoracic ratio >0.55, or pulmonary edema on chest radiograph). After 2,365 patient-years of follow-up, 201 patients had died, with 76 events due to progressive HF.: ResultsIndependent predictors of all-cause mortality assessed with the Cox proportional hazards model were as follows: a low standard deviation of all normal-to-normal RR intervals (SDNN); lower serum sodium and higher creatinine levels; higher cardiothoracic ratio; nonsustained ventricular tachycardia; higher left ventricular end-systolic diameter; left ventricular hypertrophy; and increasing age. Independent predictors of death specific to progressive HF were SDNN, serum sodium and creatinine levels. The hazard ratio of progressive HF death for a 10% decrease in SDNN was 1.06 (95% confidence interval [CI], 1.01 to 1.12); for a 2 mmol/l decrease in serum sodium, 1.22 (95% CI, 1.08 to 1.38); and for a 10 μmol/l increase in serum creatinine, 1.14 (95% CI, 1.09 to 1.19) (all p < 0.01).: ConclusionsIn ambulant outpatients with chronic HF, low serum sodium and SDNN and high serum creatinine identify patients at increased risk of death due to progressive HF. [Copyright &y& Elsevier]

Background: We aimed to develop a risk score incorporating heart rate variability (HRV) and traditional vital signs for the prediction of early mortality and complications in patients during the initial presentation to the emergency department (ED) with chest pain., Methods: We conducted a prospective observational study of patients with a primary complaint of chest pain at the ED of a tertiary hospital. The primary outcome was a composite of mortality, cardiac arrest, ventricular tachycardia, hypotension requiring inotropes or intraaortic balloon pump insertion, intubation or mechanical ventilation, complete heart block, bradycardia requiring pacing, and recurrent ischemia requiring revascularization, all within 72 hours of arrival at ED., Results: Three hundred nine patients were recruited, and 25 patients met the primary outcome. Backwards stepwise logistic regression was used to derive a scoring model that included heart rate, systolic blood pressure, respiratory rate, and low frequency to high frequency ratio. For predicting complications within 72 hours, the risk score performed with an area under the curve of 0.835 (95% confidence interval [CI], 0.749-0.920); and a cutoff of 4 and higher in the risk score gave a sensitivity of 0.880 (95% CI, 0.677-0.968), specificity of 0.680 (95% CI, 0.621-0.733), positive predictive value of 0.195, and negative predictive value of 0.985. The risk score performed better than ST elevation/depression and troponin T in predicting complications within 72 hours., Conclusion: A risk score incorporating heart rate variability and vital signs performed well in predicting mortality and other complications within 72 hours after arrival at ED in patients with chest pain., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Cell-penetrating peptides (CPPs) are a class of short, often cationic peptides that have the capability to translocate across cellular membranes, and although the translocation most likely involves several pathways, they interact directly with membranes, as well as with model bilayers. Most CPPs attain a three-dimensional structure when interacting with bilayers, while they are more or less unstructured in aqueous solution. To understand the relationship between structure and the effect that CPPs have on membranes it is of great importance to investigate CPPs at atomic resolution in a suitable membrane model. Moreover, the location in bilayers is likely to be correlated with the translocation mechanism. Solution-state NMR offers a unique possibility to investigate structure, dynamics and location of proteins and peptides in bilayers. This review focuses on solution NMR as a tool for investigating CPP-lipid interactions. Structural propensities and cell-penetrating capabilities can be derived from a combination of CPP solution structures and studies of the effect that the peptides have on bilayers and the localization in a bilayer., (Copyright © 2012 Elsevier B.V. All rights reserved.)