bluuebunny/crossref_metadata_2025 huggingface dataset:
ELECTRICAL PROPERTIES OF P3HT (POLY [3-HEXYLTHIOPHENE])/n-TYPE CRYSTALLINE SILICON (n-c-Si) SOLAR CELLS
Authors: NOLASCO JAIRO C. , CASTRO-CARRANZA ALEJANDRA , IÑIGUEZ BENJAMÍN , PALLARÈS JOSEP , ESTRADA MAGALI
Published: May 2012

Au / P 3 HT (poly [3-hexylthiophene])/n-type crystalline silicon ( n - c - Si ) solar cells have been fabricated. The Aluminum back contact is obtained by evaporation on silicon substrate. An 80 nm P 3 HT layer thick was spin-coated on silicon substrate followed by thermal annealing. Finally golden contacts are deposited by sputtering. The best characteristics of this flawed solar cell are: V oc =0.47 V , I sc =7.42 mA / cm 2 and an efficiency of 1.29%. The area of this device is 0.07 cm2. In order to get a deep understanding of the electrical properties of the heterojunction, capacitance-voltage and current-voltage-temperature measurements have been made. A compact electrical equivalent circuit has been used to describe the dark current-voltage characteristics. It is based on the combination of two exponential mechanisms, shunt and series resistances and space-charge limited current terms. From the temperature dependence of the extracted parameters we can obtain the limiting conduction mechanism. We found that the polymeric layer limits the current not only at low voltages, through Multi-Tunneling Capture Emission, but also at high voltages, through series resistance and Space-Charge Limited Current. On the other hand, the Silicon wafer limits the current at medium voltages, through the diffusion mechanism. In addition, the model is useful to estimate the open circuit voltage and built in voltage of the solar cell using only dark current voltage measurements.
FABRICATION OF FLEXIBLE FIELD-EFFECT TRANSISTORS ON 25 μm PEN FOIL
Authors: FURTHNER FRANÇOIS , PÉTER MÁRIA , VAN DER PUTTEN BAS , GELINCK GERWIN H. , MEINDERS ERWIN R. , GEUNS TOM C. T. , DE LAAT WIM
Published: May 2012

The development of high performance thin-film transistors on flexible plastic substrates is of great importance for the manufacturing and industrialization of flexible electronic devices, such as flexible displays. Here we present different approaches to fabricate bottom-gate field-effect transistors on 25 μm heat stabilized polyethylene naphthalate (PEN) foil using photolithography and solution processing. The flexibility and dimensional instability of the substrate constituted the main challenge during manufacturing. We developed a novel method to handle the foils during processing by reversibly attaching them onto 6 inch Si wafers. The so-called foil-on-carrier assembly showed excellent flatness (about 1 μm) and good dimensional stability and tolerance towards the different processing steps up to 160°C. Transistors were made either using an organic polymer or an inorganic oxide as gate dielectric material. Source and drain gold electrodes were patterned using standard photoresist patterning followed by wet etching, or by lift-off. The feature sizes in the transistors were downsized from 5 μm to sub-micrometer to improve the performance. In order to achieve structures with high resolution, all functional layers were patterned using a commercial wafer stepper (PAS5500/100D). The two dielectric materials used and the two ways of making the source-drain resulted in four different metal-insulator-metal (MIM) stacks. The MIM stacks were characterized by optical microscopy, scanning electron microscopy and four point resistance measurements. Registration accuracies below 0.5 μm were found over the whole wafer. Transistor fabrication was finished by depositing pentacene derivatives from solution.
METHODOLOGY AND TOOLS FOR INKJET PROCESS ABSTRACTION FOR THE DESIGN OF FLEXIBLE AND ORGANIC ELECTRONICS
Authors: MUJAL JORDI , RAMON ELOI , CARRABINA JORDI
Published: May 2012

Inkjet printing is a promising and challenging technique that could potentially revolutionize large area and organic electronics fabrication. Inkjet systems are designed to construct devices and circuits drop by drop, which would lead to a new paradigm in electronics fabrication. However, inkjet technology for Printed Electronics is still under development and several challenges remain. While there is significant progress being made in the development of electronic devices, such as transistors or sensors, there is a lack of work on circuit and system level design. Designing devices and circuits implies a wide knowledge of process aspects, requiring a complex interaction among concepts, tools and processes coming from different science and engineering disciplines. An explicit methodology is needed to separate design from fabrication in a similar way as in silicon design, to design devices and systems without a deep knowledge of process and materials; thus making it possible to open up inkjet technology to a larger community and undergo more rapid design implementations. In this paper we present the main aspects of such a methodology and we discuss the key topics on inkjet technology that allow us to propose these new specific steps.
SYM ANOMALOUS DIMENSION FROM OPEN STRING ENGINEERED CURVATURE
Authors: PARK I. Y.
Published: May 2012

In the full type IIB open superstring setup, we show that there exists a vertex operator, denoted by VL, whose renormalization reproduces the same anomalous dimension matrix that was obtained by Minahan and Zarembo (MZ) [J. High Energy Phys. 0303, 013 (2003)]. The vertex operator is a gauge singlet, and has the same SO(6) index structure as the operator used by MZ. To obtain the SYM anomalous dimensions, one of the key ingredients is the non-abelianization of the nonlinear sigma model action in a D-brane background. Park [Phys. Lett. B 660, 583 (2008)] conjectured that quantum effects of open strings on a stack of D-branes should generate the curvature. Even though the conjecture had passed a few consistency checks, the role of the higher order curvature terms has remain mostly unobserved until now. By choosing a special form of the non-abelianized counter vertex, VG, we show that the SYM result is reproduced. We comment on fermionic completion of VL and on how the special form of the non-Abelian vertex VG may arise.
MASS SHELL SMEARING EFFECTS IN TOP PAIR PRODUCTION
Authors: KUKSA V. I. , PASECHNIK R. S. , VLASENKO D. E.
Published: May 2012

The top quark pair production and decay are considered in the framework of the smeared-mass unstable particles model. The results for total and differential cross-sections in vicinity of [Formula: see text] threshold are in good agreement with the previous ones in the literature. The strategy of calculations of the higher order corrections in the framework of the model is discussed. Suggested approach significantly simplifies calculations compared to the standard perturbative one and can serve as a convenient tool for fast and precise preliminary analysis of processes involving intermediate timelike top quark exchanges in the near-threshold region.
EQUIVALENT SECOND-ORDER GRAVITY THEORY WITH A NONANALYTIC LAGRANGIAN THAT BEHAVES AS A PERFECT FLUID HAVING CHARACTERISTIC DENSITY AND PRESSURE
Authors: MAJUMDAR PRIYADARSHI
Published: May 2012

We formulate a modified theory of gravity and equivalent second-order gravity theory for a Lagrangian containing R and [Formula: see text] term in spatially homogeneous and isotropic background. The [Formula: see text] term in the action can be thought of as equivalent to a source term in Einstein's gravity, which can be assumed to be equivalent with a perfect fluid characterized by density ρ and pressure p. The pressure p is a function of ρ, scale factor a and the curvature parameter R. We present a few analytical solutions of evolution equation for deceleration parameter q as a function of p and ρ.
APPLICABILITY OF PARALLEL PLATE AVALANCHE COUNTERS TO SPONTANEOUS FISSION FROM 252Cf
Authors: YASIN ZAFAR , HANSEN KURT , LUNDIN MAGNUS , RASSOL ROGER , ISAKSSON LENNART , SCHRODER BENT
Published: May 2012

The construction and performance of the parallel plate avalanche counters (PPACs) using a spontaneous fission source 252 Cf is described in this paper. The parallel plate circular electrodes are made of aluminum foils having a thickness less than ten microns. After fabrication, the detectors and the source are mounted inside a reaction chamber, the source between the two detectors. A low pressure is created inside the chamber using isobutane ( C 4 H 10) and a high voltage is applied to the electrodes. The detectors are first operated at different pressures and voltages to find the optimum values of the pressure and the voltage. This is necessary to avoid the sparking threshold, to achieve a good time resolution and to keep the gain of the detectors high and constant. The PPACs are operated in 2π- and 4π-geometries. In 4π-geometry the detectors are allowed to function in coincidence and noncoincidence mode. The resulting pulse height and the time spectra are studied using the computer code ROOT and some conclusions are drawn from these analyses. The pulse height spectrum shows a clear separation between the fission fragments and the alpha particles and the time spectrum indicates a good intrinsic time resolution, 0.76 ns.
OPTIMAL GEOMETRIC PROCESS REPLACEMENT POLICIES BASED ON NUMBER OF DOWN TIMES
Authors: HANAGAL DAVID D. , KANADE RUPALI A.
Published: May 2012

We consider two repair-replacement policies for a cold standby system consisting of two components with a single repairman. It is assumed that each component after repair is not "as good as new". With this assumption by using geometric process we developed two replacement policies based on the number of down times of the component-1. Our problem is to choose optimal replacement policy (k) such that the long run expected reward per unit time of the system maximized. The mathematical expressions for the long run expected reward per unit time are evaluated and corresponding optimal replacement policies are obtained theoretically with numerical example and by simulation study. Also we have discussed Newton–Raphson method to find optimal k.
A FRAMEWORK FOR CAPTURING DEGRADATION BEHAVIOR IN RELIABILITY-BASED ROBUST DESIGN OPTIMIZATION
Authors: YADAV OM PRAKASH , BHAMARE SUNIL S. , RATHORE AJAY PAL SINGH
Published: May 2012

The increasing customer awareness and global competition have forced manufacturers to capture the entire life cycle issues during product design and development stage. The thorough understanding of product behavior (degradation process) and various uncertainties associated with product performance is paramount to produce reliable and robust design. This paper proposes a multi-objective framework for reliability-based robust design optimization, which captures degradation behavior of quality characteristics to provide optimal design parameters. The objective function of the multi-objective optimization problem is defined as quality loss function considering both desirable and undesirable deviations between target values and the actual results. The degradation behavior is captured by using empirical model to estimate amount of degradation accumulated in time t. The applicability of the proposed methodology is demonstrated by considering a leaf spring design problem.
NON-PRINCIPAL ULTRAFILTERS, PROGRAM EXTRACTION AND HIGHER-ORDER REVERSE MATHEMATICS
Authors: KREUZER ALEXANDER P.
Published: May 2012

We investigate the strength of the existence of a non-principal ultrafilter over fragments of higher-order arithmetic. Let [Formula: see text] be the statement that a non-principal ultrafilter on ℕ exists and let [Formula: see text] be the higher-order extension of ACA0. We show that [Formula: see text] is [Formula: see text]-conservative over [Formula: see text] and thus that [Formula: see text] is conservative over PA. Moreover, we provide a program extraction method and show that from a proof of a strictly [Formula: see text] statement ∀ f ∃ g A qf(f, g) in [Formula: see text] a realizing term in Gödel's system T can be extracted. This means that one can extract a term t ∈ T, such that ∀ f A qf(f, t(f)).
Use of FTIR for Rapid Authentication and Detection of Adulteration of Food
Authors: Rodriguez-Saona L.E. , Allendorf M.E.
Published: May 2012

Fourier transform infrared (FTIR) spectroscopy is an appealing technology for the food industry because simple, rapid, and nondestructive measurements of chemical and physical components can be obtained. Advances in FTIR instrumentation combined with the development of powerful multivariate data analysis methods make this technology ideal for large volume, rapid screening and characterization of minor food components down to parts per billion (ppb) levels. Because of the use of FTIR techniques in quality and process control applications, the food industry is already familiar with the technology and its potential to expand to monitoring for food adulteration. The aim of this review is to compile the current research on applications of near infrared (NIR) and mid-infrared (MIR) spectroscopy for rapid authentication and detection of adulteration in food.
Biochemical Basis for Functional Ingredient Design from Fruits
Authors: Jacob Jissy K. , Tiwari Krishnaraj , Correa-Betanzo Julieta , Misran Azizah , Chandrasekaran Renu , Paliyath Gopinadhan
Published: May 2012

Functional food ingredients (nutraceuticals) in fruits range from small molecular components, such as the secondary plant products, to macromolecular entities, e.g., pectin and cellulose, that provide several health benefits. In fruits, the most visible functional ingredients are the color components anthocyanins and carotenoids. In addition, several other secondary plant products, including terpenes, show health beneficial activities. A common feature of several functional ingredients is their antioxidant function. For example, reactive oxygen species (ROS) can be oxidized and stabilized by flavonoid components, and the flavonoid radical can undergo electron rearrangement stabilizing the flavonoid radical. Compounds that possess an orthodihydroxy or quinone structure can interact with cellular proteins in the Keap1/Nrf2/ARE pathway to activate the gene transcription of antioxidant enzymes. Carotenoids and flavonoids can also exert their action by modulating the signal transduction and gene expression within the cell. Recent results suggest that these activities are primarily responsible for the health benefits associated with the consumption of fruits and vegetables.
Challenges for the Delivery of Long-Chain n-3 Fatty Acids in Functional Foods
Authors: Taneja Amit , Singh Harjinder
Published: May 2012

Extensive research has shown that increased consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 LCPUFAs), namely α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), may lower the risk of chronic diseases, such as heart disease, cancer, and arthritis. Given that Western diets are deficient in n-3 LCPUFAs, enrichment of food products is seen as an alternative for increasing the intake of these fatty acids. However, because of the high instability of these fatty acids to oxidative deterioration, enrichment of foods with n-3 LCPUFAs has been technically challenging. This review provides an overview of different technical approaches that have been taken to overcome oxidation-related problems. This review also looks at the challenges faced by health organizations, food manufacturers, and food scientists for the delivery of long-chain n-3 fatty acids in functional foods.
Encapsulation of New Active Ingredients
Authors: Onwulata C.I.
Published: May 2012

The organic construct consumed as food comes packaged in units that carry the active components and protect the entrapped active materials until delivered to targeted human organs. The packaging and delivery role is mimicked in the microencapsulation tools used to deliver active ingredients in processed foods. Microencapsulation efficiency is balanced against the need to access the entrapped nutrients in bioavailable forms. Encapsulated ingredients boosted with bioactive nutrients are intended for improved health and well-being and to prevent future health problems. Presently, active ingredients are delivered using new techniques, such as hydrogels, nanoemulsions, and nanoparticles. In the future, nutraceuticals and functional foods may be tailored to individual metabolic needs and tied to each person's genetic makeup. Bioactive ingredients provide health-enhancing nutrients and are protected through encapsulation processes that shield the active ingredients from deleterious environments.
Functional Replacements for Gluten
Authors: Zannini Emanuele , Jones Julie Miller , Renzetti Stefano , Arendt Elke K
Published: May 2012

Celiac disease (CD) is an immune-mediated disease triggered in genetically susceptible individuals by ingested gluten from wheat, rye, barley, and other closely related cereal grains. Currently, the only therapy able to normalize the clinical and histological manifestation of the disease is a strict and life-long gluten-free (GF) diet. The replacement of gluten presents a significant technological challenge, as it is an essential structure-building protein, which is necessary for formulating high-quality baked goods. The objective of this paper is to review some basics about CD, its current prevalence, and the recent advances in the preparation of high-quality GF breads using GF flours, starches, hydrocolloids, gums, and novel functional ingredients and technologies.
Health Claims in Europe: Probiotics and Prebiotics as Case Examples
Authors: van Loveren Henk , Sanz Yolanda , Salminen Seppo
Published: May 2012

Health claims regarding foods imply a relationship between a specific food and maintenance of good health, or that food can reduce the risk of disease. Health claim legislation in the European Union sets out from the concept of consumer protection. Health claim assessment focuses on defining given foods, assessing their health relationship, and evaluating relevant studies with an emphasis on controlled human intervention research. Challenges include the focus of claims on healthy populations, although most intervention studies have been conducted among patients. A further problem attends the risk reduction claim, which requires changes in generally accepted biomarkers reflecting the risk of disease. Scientific assessment and guidance documents direct the development of health claims both in Europe and elsewhere. Experience from completed assessments should make it possible to provide consumers with reliable claims to help them make healthier choices and develop lifestyles supporting long-term well-being.
The Impact of Omic Technologies on the Study of Food Microbes
Authors: O'Flaherty Sarah , Klaenhammer Todd R.
Published: May 2012

The advent of the molecular biology era in the 1950s and the subsequent emergence of new technologies positively impacted on all areas of biology. New discoveries in molecular biology and experimental tools were developed over the next 60 years that have revolutionized the study of food microbiology. Previously, food microbiology relied on classic microbiology techniques, which had remained relatively unchanged since the discoveries of Louis Pasteur in the 1800s. More recently, new advances resulting in “omic” technologies have exploded the areas of genomics, transcriptomics, and proteomics and revealed many fundamental processes driven by both pathogens and commensals. This review outlines advances in omic technologies and how these have impacted food microbiology through providing examples of recently published landmark work.
Pomegranate as a Functional Food and Nutraceutical Source
Authors: Johanningsmeier Suzanne D. , Harris G. Keith
Published: May 2012

Pomegranate, a fruit native to the Middle East, has gained widespread popularity as a functional food and nutraceutical source. The health effects of the whole fruit, as well as its juices and extracts, have been studied in relation to a variety of chronic diseases. Promising results against cardiovascular disease, diabetes, and prostate cancer have been reported from human clinical trials. The in vitro antioxidant activity of pomegranate has been attributed to its high polyphenolic content, specifically punicalagins, punicalins, gallagic acid, and ellagic acid. These compounds are metabolized during digestion to ellagic acid and urolithins, suggesting that the bioactive compounds that provide in vivo antioxidant activity may not be the same as those present in the whole food. Anthocyanins and the unique fatty acid profile of the seed oil may also play a role in pomegranate's health effects. A more complete characterization of pomegranate components and their physiological fate may provide mechanistic insight into the potential health benefits observed in clinical trials.
Mammals, Milk, Molecules, and Micelles
Authors: Fox P.F.
Published: May 2012

After a brief description of my family background and school days, my professional career as a dairy scientist is described under three headings: research, teaching, and writing. My research activities fall into four areas: biochemistry of cheese, fractionation and characterization of milk proteins, heat stability of milk, and dairy enzymology. Finally, I offer some advice to young scientists.
Alteration of ATP-sensitive K+ channels in rabbit aortic smooth muscle during left ventricular hypertrophy
Authors: Park Won Sun , Hong Da Hye , Son Youn Kyoung , Kim Min Hee , Jeong Seung Hun , Kim Hyoung Kyu , Kim Nari , Han Jin
Published: May 2012

We investigated the impairment of ATP-sensitive K+ (KATP) channels in aortic smooth muscle cells (ASMCs) from isoproterenol-induced hypertrophied rabbits. The amplitude of KATP channels induced by the KATP channel opener pinacidil (10 μM) was greater in ASMCs from control than from hypertrophied animals. In phenylephrine-preconstricted aortic rings, pinacidil induced relaxation in a dose-dependent manner. The dose-dependent curve was shifted to the right in the hypertrophied (EC50: 17.80 ± 3.28 μM) compared with the control model (EC50: 6.69 ± 2.40 μM). Although the level of Kir6.2 subtype expression did not differ between ASMCs from the control and hypertrophied models, those of the Kir6.1 and SUR2B subtypes were decreased in the hypertrophied model. Application of the calcitonin-gene related peptide (100 nM) and adenylyl cyclase activator forskolin (10 μM), which activates protein kinase A (PKA) and consequently KATP channels, induced a KATP current in both control and hypertrophied animals; however, the KATP current amplitude did not differ between the two groups. Furthermore, PKA expression was not altered between the control and hypertrophied animals. These results suggests that the decreased KATP current amplitude and KATP channel-induced vasorelaxation in the hypertrophied animals were attributable to the reduction in KATP channel expression but not to changes in the intracellular signaling mechanism that activates the KATP current.
Lipopolysaccharide-sensitive H+ current in dendritic cells
Authors: Szteyn Kalina , Yang Wenting , Schmid Evi , Lang Florian , Shumilina Ekaterina
Published: May 2012

Dendritic cells (DCs) are the most potent antigen-presenting cells equipped to transport antigens from the periphery to lymphoid tissues and to present them to T cells. Ligation of Toll-like receptor 4 (TLR4), expressed on the DC surface, by lipopolysaccharides (LPS), elements of the Gram-negative bacteria outer wall, induces DC maturation. Initial steps of maturation include stimulation of antigen endocytosis and enhanced reactive oxygen species (ROS) production with eventual downregulation of endocytic capacity in fully matured DCs. ROS production depends on NADPH oxidase (NOX2), the activity of which requires continuous pH and charge compensation. The present study demonstrates, for the first time, the functional expression of voltage-gated proton (Hv1) channels in mouse bone marrow-derived DCs. In whole cell patch-clamp experiments, we recorded Zn2+ (50 μM)-sensitive outwardly rectifying currents activated upon depolarization, which were highly selective for H+, with the reversal potential shift of 38 mV per pH unit. The threshold voltage of activation ( Vthreshold) was dependent on the pH gradient and was close to the empirically predicted Vthreshold for the Hv1 currents. LPS (1 μg/ml) had bimodal effects on Hv1 channels: acute LPS treatment increased Hv1 channel activity, whereas 24 h of LPS incubation significantly inhibited Hv1 currents and decreased ROS production. Activation of H+ currents by acute application of LPS was abolished by PKC inhibitor GFX (10 nM). According to electron current measurements, acute LPS application was associated with increased NOX2 activity.
Cystic fibrosis transmembrane conductance regulator contributes to reacidification of alkalinized lysosomes in RPE cells
Authors: Liu Ji , Lu Wennan , Guha Sonia , Baltazar Gabriel C. , Coffey Erin E. , Laties Alan M. , Rubenstein Ronald C. , Reenstra William W. , Mitchell Claire H.
Published: May 2012

The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in lysosomal acidification has been difficult to determine. We demonstrate here that CFTR contributes more to the reacidification of lysosomes from an elevated pH than to baseline pH maintenance. Lysosomal alkalinization is increasingly recognized as a factor in diseases of accumulation, and we previously showed that cAMP reacidified alkalinized lysosomes in retinal pigmented epithelial (RPE) cells. As the influx of anions to electrically balance proton accumulation may enhance lysosomal acidification, the contribution of the cAMP-activated anion channel CFTR to lysosomal reacidification was probed. The antagonist CFTRinh-172 had little effect on baseline levels of lysosomal pH in cultured human RPE cells but substantially reduced the reacidification of compromised lysosomes by cAMP. Likewise, CFTR activators had a bigger impact on cells whose lysosomes had been alkalinized. Knockdown of CFTR with small interfering RNA had a larger effect on alkalinized lysosomes than on baseline levels. Inhibition of CFTR in isolated lysosomes altered pH. While CFTR and Lamp1 were colocalized, treatment with cAMP did not increase targeting of CFTR to the lysosome. The inhibition of CFTR slowed lysosomal degradation of photoreceptor outer segments while activation of CFTR enhanced their clearance from compromised lysosomes. Activation of CFTR acidified RPE lysosomes from the ABCA4−/− mouse model of recessive Stargardt's disease, whose lysosomes are considerably alkalinized. In summary, CFTR contributes more to reducing lysosomal pH from alkalinized levels than to maintaining baseline pH. Treatment to activate CFTR may thus be of benefit in disorders of accumulation associated with lysosomal alkalinization.
ZnT-1 enhances the activity and surface expression of T-type calcium channels through activation of Ras-ERK signaling
Authors: Mor Merav , Beharier Ofer , Levy Shiri , Kahn Joy , Dror Shani , Blumenthal Daniel , Gheber Levi A. , Peretz Asher , Katz Amos , Moran Arie , Etzion Yoram
Published: May 2012

Zinc transporter-1 (ZnT-1) is a putative zinc transporter that confers cellular resistance from zinc toxicity. In addition, ZnT-1 has important regulatory functions, including inhibition of L-type calcium channels and activation of Raf-1 kinase. Here we studied the effects of ZnT-1 on the expression and function of T-type calcium channels. In Xenopus oocytes expressing voltage-gated calcium channel (CaV) 3.1 or CaV3.2, ZnT-1 enhanced the low-threshold calcium currents ( IcaT) to 182 ± 15 and 167.95 ± 9.27% of control, respectively ( P < 0.005 for both channels). As expected, ZnT-1 also enhanced ERK phosphorylation. Coexpression of ZnT-1 and nonactive Raf-1 blocked the ZnT-1-mediated ERK phosphorylation and abolished the ZnT-1-induced augmentation of IcaT. In mammalian cells (Chinese hamster ovary), coexpression of CaV3.1 and ZnT-1 increased the IcaT to 166.37 ± 6.37% compared with cells expressing CaV3.1 alone ( P < 0.01). Interestingly, surface expression measurements using biotinylation or total internal reflection fluorescence microscopy indicated marked ZnT-1-induced enhancement of CaV3.1 surface expression. The MEK inhibitor PD-98059 abolished the ZnT-1-induced augmentation of surface expression of CaV3.1. In cultured murine cardiomyocytes (HL-1 cells), transient exposure to zinc, leading to enhanced ZnT-1 expression, also enhanced the surface expression of endogenous CaV3.1 channels. Consistently, in these cells, endothelin-1, a potent activator of Ras-ERK signaling, enhanced the surface expression of CaV3.1 channels in a PD-98059-sensitive manner. Our findings indicate that ZnT-1 enhances the activity of CaV3.1 and CaV3.2 through activation of Ras-ERK signaling. The augmentation of CaV3.1 currents by Ras-ERK activation is associated with enhanced trafficking of the channel to the plasma membrane.
Growth and regression of vasculature in healthy and diabetic mice after hindlimb ischemia
Authors: Landázuri Natalia , Joseph Giji , Guldberg Robert E. , Taylor W. Robert
Published: May 2012

The formation of vascular networks during embryogenesis and early stages of development encompasses complex and tightly regulated growth of blood vessels, followed by maturation of some vessels, and spatially controlled disconnection and pruning of others. The adult vasculature, while more quiescent, is also capable of adapting to changing physiological conditions by remodeling blood vessels. Numerous studies have focused on understanding key factors that drive vessel growth in the adult in response to ischemic injury. However, little is known about the extent of vessel rarefaction and its potential contribution to the final outcome of vascular recovery. We addressed this topic by characterizing the endogenous phases of vascular repair in a mouse model of hindlimb ischemia. We showed that this process is biphasic. It encompasses an initial rapid phase of vessel growth, followed by a later phase of vessel rarefaction. In healthy mice, this process resulted in partial recovery of perfusion and completely restored the ability of mice to run voluntarily. Given that the ability to revascularize can be compromised by a cardiovascular risk factor such as diabetes, we also examined vascular repair in diabetic mice. We found that paradoxically both the initial growth and subsequent regression of collateral vessels were more pronounced in the setting of diabetes and resulted in impaired recovery of perfusion and impaired functional status. In conclusion, our findings demonstrate that the formation of functional collateral vessels in the hindlimb requires vessel growth and subsequent vessel rarefaction. In the setting of diabetes, the physiological defect was not in the initial formation of vessels but rather in the inability to sustain newly formed vessels.
Human apolipoprotein E4 targeted replacement in mice reveals increased susceptibility to sleep disruption and intermittent hypoxia
Authors: Kaushal Navita , Ramesh Vijay , Gozal David
Published: May 2012

Intermittent hypoxia (IH) and sleep fragmentation (SF) are major manifestations of sleep apnea, a frequent condition in aging humans. Sleep perturbations are frequent in Alzheimer's disease (AD) and may underlie the progression of disease. We hypothesized that acute short-term IH, SF, and their combination (IH+SF) may reveal unique susceptibility in sleep integrity in a murine model of AD. The effects of acute IH, SF, and IH+SF on sleep architecture, delta power, sleep latency, and core body temperature were assessed in adult male human ApoE4-targeted replacement mice (hApoE4) and wild-type (WT) controls. Slow wave sleep (SWS) was significantly reduced, and rapid eye movement (REM) sleep was almost abolished during acute exposure to IH alone and IH+SF for 6 h in hApoE4, with milder effects in WT controls. Decreased delta power during SWS did not show postexposure rebound in hApoE4 unlike WT controls. IH and IH+SF induced hypothermia, which was more prominent in hApoE4 than WT controls. Mice subjected to SF also showed sleep deficits but without hypothermia. hApoE4 mice, unlike WT controls, exhibited increased sleep propensity, especially following IH and IH+SF, suggesting limited ability for sleep recovery in hApoE4 mice. These findings substantiate the potential impact of IH and SF in modulating sleep architecture and sleep homeostasis including maintenance of body temperature. Furthermore, the increased susceptibility and limited recovery ability of hApoE4 mice to sleep apnea suggests that early recognition and treatment of the latter in AD patients may restrict the progression and clinical manifestations of this frequent neurodegenerative disorder.
High nephron endowment protects against salt-induced hypertension
Authors: Walker Kenneth A. , Cai Xiaochu , Caruana Georgina , Thomas Merlin C. , Bertram John F. , Kett Michelle M.
Published: May 2012

While low nephron number is associated with increased risk of developing cardiovascular and renal disease, the functional consequences of a high nephron number are unknown. We tested the hypothesis that a high nephron number provides protection against hypertensive and renal insults. Mean arterial pressure (MAP) and renal function were characterized in male wild-type (WT) and transforming growth factor-β2 heterozygous ( Tgfb2+/−) mice under basal conditions and following a chronic high-salt diet. Kidneys were collected for unbiased stereological analysis. Baseline MAP and renal function were indistinguishable between genotypes. The chronic high-salt diet (5% NaCl for 4 wk followed by 8% NaCl for 4 wk) led to similar step-wise increases in urine volume, Na+excretion, and albuminuria in the genotypes. The 5% NaCl diet induced modest and similar increases in MAP (3.5 ± 1.6 and 3.4 ± 0.8 mmHg in WT and Tgfb2+/−, respectively). After the step up to the 8% NaCl diet, MAP increased further in WT (+15.9 ± 5.1 mmHg), but not Tgfb2+/−(−0.1 ± 1.0 mmHg), mice. Nephron number was 30% greater in Tgfb2+/−than WT mice and was not affected by the chronic high-salt diet. Mean glomerular volume was lower in Tgfb2+/−than WT mice, and the chronic high-salt diet induced significant glomerular hypertrophy. In a separate cohort of mice, an acute, 7-day, 8% NaCl diet induced similar rises in MAP in the genotypes. This is the first study to examine the physiological characteristics of a model of high nephron number, and the findings are consistent with this phenotype providing protection against chronic, but not acute, hypertensive insults.
Functional significance of conserved cysteines in the human organic cation transporter 2
Authors: Pelis Ryan M. , Dangprapai Yodying , Cheng Yaofeng , Zhang Xiaohong , Terpstra Jennifer , Wright Stephen H.
Published: May 2012

The significance of conserved cysteines in the human organic cation transporter 2 (hOCT2), namely the six cysteines in the long extracellular loop (loop cysteines) and C474 in transmembrane helix 11, was examined. Uptake of tetraethylammonium (TEA) and 1-methyl-4-phenypyridinium (MPP) into Chinese hamster ovary cells was stimulated >20-fold by hOCT2 expression. Both cell surface expression and transport activity were reduced considerably following mutation of individual loop cysteines (C51, C63, C89, C103, and C143), and the C89 and C103 mutants had reduced Michaelis constants ( Kt) for MPP. The loop cysteines were refractory to interaction with thiol-reactive biotinylation reagents, except after pretreatment of intact cells with dithiothreitol or following cell membrane solubilization. Reduction of disulfide bridge(s) did not affect transport, but labeling the resulting free thiols with maleimide-PEO2-biotin did. Mutation of C474 to an alanine or phenylalanine did not affect the Ktvalue for MPP. In contrast, the Ktvalue associated with TEA transport was reduced sevenfold in the C474A mutant, and the C474F mutant failed to transport TEA. This study shows that some but not all of the six extracellular loop cysteines exist within disulfide bridge(s). Each loop cysteine is important for plasma membrane targeting, and their mutation can influence substrate binding. The effect of C474 mutation on TEA transport suggests that it contributes to a TEA binding surface. Given that TEA and MPP are competitive inhibitors, the differential effects of C474 modification on TEA and MPP binding suggest that the binding surfaces for each are distinct, but overlapping in area.
Proximal tubule haptoglobin gene activation is an integral component of the acute kidney injury “stress response”
Authors: Zager Richard A. , Vijayan Anitha , Johnson Ali C. M.
Published: May 2012

Haptoglobin (Hp) synthesis occurs almost exclusively in liver, and it is rapidly upregulated in response to stress. Because many of the pathways that initiate hepatic Hp synthesis are also operative during acute kidney injury (AKI), we tested whether AKI activates the renal cortical Hp gene. CD-1 mice were subjected to six diverse AKI models: ischemia-reperfusion, glycerol injection, cisplatin nephrotoxicity, myoglobinuria, endotoxemia, and bilateral ureteral obstruction. Renal cortical Hp gene induction was determined either 4–72 h or 1–3 wk later by measuring Hp mRNA and protein levels. Relative renal vs. hepatic Hp gene induction during endotoxemia was also assessed. Each form of AKI induced striking and sustained Hp mRNA increases, leading to ∼10- to 100-fold renal Hp protein elevations (ELISA; Western blot). Immunohistochemistry, and isolated proximal tubule assessments, indicated that the proximal tubule was the dominant (if not only) site of the renal Hp increases. Corresponding urinary and plasma Hp elevations were surrogate markers of this response. Endotoxemia evoked 25-fold greater Hp mRNA increases in kidney vs. liver, indicating marked renal Hp gene reactivity. Clinical relevance of these findings was suggested by observations that urine samples from 16 patients with established AKI had statistically higher (∼12×) urinary Hp levels than urine samples from either normal subjects or from 15 patients with chronic kidney disease. These AKI-associated urinary Hp increases mirrored those seen for urinary neutrophil gelatinase-associated lipoprotein, a well accepted AKI biomarker gene. In summary, these studies provide the first evidence that AKI evokes rapid, marked, and sustained induction of the proximal tubule Hp gene. Hp's known antioxidant, as well as its protean pro- and anti-inflammatory, actions imply potentially diverse effects on the evolution of acute tubular injury.
Hypotonic stress upregulates β- and γ-ENaC expression through suppression of ERK by inducing MKP-1
Authors: Niisato Naomi , Ohta Mariko , Eaton Douglas C. , Marunaka Yoshinori
Published: May 2012

We investigated a physiological role for ERK, a member of the MAPK family, in the hypotonic stimulation of epithelial Na+ channel (ENaC)-mediated Na+ reabsorption in renal epithelial A6 cells. We show that hypotonic stress causes a major dephosphorylation of ERK following a rapid transient phosphorylation. PD98059 (a MEK inhibitor) increases dephosphorylated ERK and enhances the hypotonic-stress-stimulated Na+ reabsorption. ERK dephosphorylation is mediated by MAPK phosphatase (MKP). Hypotonic stress activates p38, which in turn induces MKP-1 and to a lesser extent MKP-3 mRNA expression. Inhibition of p38 suppresses MKP-1 induction, preventing hypotonic stress from dephosphorylating ERK. Inhibition of MKP-1 and -3 by the inhibitor NSC95397 also suppresses the hypotonicity-induced dephosphorylation of ERK. NSC95397 reduces both β- and γ-ENaC mRNA expression and ENaC-mediated Na+ reabsorption stimulated by hypotonic stress. In contrast, pretreatment with PD98059 significantly enhances mRNA and protein expression of β- and γ-ENaC even under isotonic conditions. However, PD98059 only stimulates Na+ reabsorption in response to hypotonic stress, suggesting that ERK inactivation by itself (i.e., under isotonic conditions) is not sufficient to stimulate Na+ reabsorption, even though ERK inactivation enhances β- and γ-ENaC expression. Based on these results, we conclude that hypotonic stress stimulates Na+ reabsorption through at least two signaling pathways: 1) induction of MKP-1 that suppresses ERK activity and induces β- and γ-ENaC expression, and 2) promotion of translocation of the newly synthesized ENaC to the apical membrane.
ER stress contributes to renal proximal tubule injury by increasing SREBP-2-mediated lipid accumulation and apoptotic cell death
Authors: Lhoták Šárka , Sood Sudesh , Brimble Elise , Carlisle Rachel E. , Colgan Stephen M. , Mazzetti Adam , Dickhout Jeffrey G. , Ingram Alistair J. , Austin Richard C.
Published: May 2012

Renal proximal tubule injury is induced by agents/conditions known to cause endoplasmic reticulum (ER) stress, including cyclosporine A (CsA), an immunosuppressant drug with nephrotoxic effects. However, the underlying mechanism by which ER stress contributes to proximal tubule cell injury is not well understood. In this study, we report lipid accumulation, sterol regulatory element-binding protein-2 (SREBP-2) expression, and ER stress in proximal tubules of kidneys from mice treated with the classic ER stressor tunicamycin (Tm) or in human renal biopsy specimens showing CsA-induced nephrotoxicity. Colocalization of ER stress markers [78-kDa glucose regulated protein (GRP78), CHOP] with SREBP-2 expression and lipid accumulation was prominent within the proximal tubule cells exposed to Tm or CsA. Prolonged ER stress resulted in increased apoptotic cell death of lipid-enriched proximal tubule cells with colocalization of GRP78, SREBP-2, and Ca2+-independent phospholipase A2(iPLA2β), an SREBP-2 inducible gene with proapoptotic characteristics. In cultured HK-2 human proximal tubule cells, CsA- and Tm-induced ER stress caused lipid accumulation and SREBP-2 activation. Furthermore, overexpression of SREBP-2 or activation of endogenous SREBP-2 in HK-2 cells stimulated apoptosis. Inhibition of SREBP-2 activation with the site-1-serine protease inhibitor AEBSF prevented ER stress-induced lipid accumulation and apoptosis. Overexpression of the ER-resident chaperone GRP78 attenuated ER stress and inhibited CsA-induced SREBP-2 expression and lipid accumulation. In summary, our findings suggest that ER stress-induced SREBP-2 activation contributes to renal proximal tubule cell injury by dysregulating lipid homeostasis.
Episodic swimming in the larval zebrafish is generated by a spatially distributed spinal network with modular functional organization
Authors: Wiggin Timothy D. , Anderson Tatiana M. , Eian John , Peck Jack H. , Masino Mark A.
Published: May 2012

Despite the diverse methods vertebrates use for locomotion, there is evidence that components of the locomotor central pattern generator (CPG) are conserved across species. When zebrafish begin swimming early in development, they perform short episodes of activity separated by periods of inactivity. Within these episodes, the trunk flexes with side-to-side alternation and the traveling body wave progresses rostrocaudally. To characterize the distribution of the swimming CPG along the rostrocaudal axis, we performed transections of the larval zebrafish spinal cord and induced fictive swimming using N-methyl-d-aspartate (NMDA). In both intact and spinalized larvae, bursting is found throughout the rostrocaudal extent of the spinal cord, and the properties of fictive swimming observed were dependent on the concentration of NMDA. We isolated series of contiguous spinal segments by performing multiple spinal transections on the same larvae. Although series from all regions of the spinal cord have the capacity to produce bursts, the capacity to produce organized episodes of fictive swimming has a rostral bias: in the rostral spinal cord, only 12 contiguous body segments are necessary, whereas 23 contiguous body segments are necessary in the caudal spinal cord. Shorter series of segments were often active but produced either continuous rhythmic bursting or sporadic, nonrhythmic bursting. Both episodic and continuous bursting alternated between the left and right sides of the body and showed rostrocaudal progression, demonstrating the functional dissociation of the circuits responsible for episodic structure and fine burst timing. These findings parallel results in mammalian locomotion, and we propose a hierarchical model of the larval zebrafish swimming CPG.
Neural control of rhythmic arm cycling after stroke
Authors: Zehr E. Paul , Loadman Pamela M. , Hundza Sandra R.
Published: May 2012

Disordered reflex activity and alterations in the neural control of walking have been observed after stroke. In addition to impairments in leg movement that affect locomotor ability after stroke, significant impairments are also seen in the arms. Altered neural control in the upper limb can often lead to altered tone and spasticity resulting in impaired coordination and flexion contractures. We sought to address the extent to which the neural control of movement is disordered after stroke by examining the modulation pattern of cutaneous reflexes in arm muscles during arm cycling. Twenty-five stroke participants who were at least 6 mo postinfarction and clinically stable, performed rhythmic arm cycling while cutaneous reflexes were evoked with trains (5 × 1.0-ms pulses at 300 Hz) of constant-current electrical stimulation to the superficial radial (SR) nerve at the wrist. Both the more (MA) and less affected (LA) arms were stimulated in separate trials. Bilateral electromyography (EMG) activity was recorded from muscles acting at the shoulder, elbow, and wrist. Analysis was conducted on averaged reflexes in 12 equidistant phases of the movement cycle. Phase-modulated cutaneous reflexes were present, but altered, in both MA and LA arms after stroke. Notably, the pattern was “blunted” in the MA arm in stroke compared with control participants. Differences between stroke and control were progressively more evident moving from shoulder to wrist. The results suggest that a reduced pattern of cutaneous reflex modulation persists during rhythmic arm movement after stroke. The overall implication of this result is that the putative spinal contributions to rhythmic human arm movement remain accessible after stroke, which has translational implications for rehabilitation.
Synthesis of Silica Nanoparticles by Sol‐Gel: Size‐Dependent Properties, Surface Modification, and Applications in Silica‐Polymer Nanocomposites—A Review
Authors: Rahman Ismail Ab , Padavettan Vejayakumaran
Published: May 2012

Application of silica nanoparticles as fillers in the preparation of nanocomposite of polymers has drawn much attention, due to the increased demand for new materials with improved thermal, mechanical, physical, and chemical properties. Recent developments in the synthesis of monodispersed, narrow‐size distribution of nanoparticles by sol‐gel method provide significant boost to development of silica‐polymer nanocomposites. This paper is written by emphasizing on the synthesis of silica nanoparticles, characterization on size‐dependent properties, and surface modification for the preparation of homogeneous nanocomposites, generally by sol‐gel technique. The effect of nanosilica on the properties of various types of silica‐polymer composites is also summarized.
A Numerical Method of Reduced Complexity for Simulating Vascular Hemodynamics Using Coupled 0D Lumped and 1D Wave Propagation Models
Authors: Kroon Wilco , Huberts Wouter , Bosboom Marielle , van de Vosse Frans
Published: May 2012

A computational method of reduced complexity is developed for simulating vascular hemodynamics by combination of one-dimensional (1D) wave propagation models for the blood vessels with zero-dimensional (0D) lumped models for the microcirculation. Despite the reduced dimension, current algorithms used to solve the model equations and simulate pressure and flow are rather complex, thereby limiting acceptance in the medical field. This complexity mainly arises from the methods used to combine the 1D and the 0D model equations. In this paper a numerical method is presented that no longer requires additional coupling methods and enables random combinations of 1D and 0D models using pressure as only state variable. The method is applied to a vascular tree consisting of 60 major arteries in the body and the head. Simulated results are realistic. The numerical method is stable and shows good convergence.