bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-lived crowded-litter mice exhibit lasting effects on insulin sensitivity and energy homeostasis
Authors: Sadagurski Marianna , Landeryou Taylor , Blandino-Rosano Manuel , Cady Gillian , Elghazi Lynda , Meister Daniel , See Lauren , Bartke Andrzej , Bernal-Mizrachi Ernesto , Miller Richard A.
Published: April 2014

The action of nutrients on early postnatal growth can influence mammalian aging and longevity. Recent work has demonstrated that limiting nutrient availability in the first 3 wk of life [by increasing the number of pups in the crowded-litter (CL) model] leads to extension of mean and maximal lifespan in genetically normal mice. In this study, we aimed to characterize the impact of early-life nutrient intervention on glucose metabolism and energy homeostasis in CL mice. In our study, we used mice from litters supplemented to 12 or 15 pups and compared those to control litters limited to eight pups. At weaning and then throughout adult life, CL mice are significantly leaner and consume more oxygen relative to control mice. At 6 mo of age, CL mice had low fasting leptin concentrations, and low-dose leptin injections reduced body weight and food intake more in CL female mice than in controls. At 22 mo, CL female mice also have smaller adipocytes compared with controls. Glucose and insulin tolerance tests show an increase in insulin sensitivity in 6 mo old CL male mice, and females become more insulin sensitive later in life. Furthermore, β-cell mass was significantly reduced in the CL male mice and was associated with reduction in β-cell proliferation rate in these mice. Together, these data show that early-life nutrient intervention has a significant lifelong effect on metabolic characteristics that may contribute to the increased lifespan of CL mice.
The role of active muscle mass in determining the magnitude of peripheral fatigue during dynamic exercise
Authors: Rossman Matthew J. , Garten Ryan S. , Venturelli Massimo , Amann Markus , Richardson Russell S.
Published: April 2014

Greater peripheral quadriceps fatigue at the voluntary termination of single-leg knee-extensor exercise (KE), compared with whole-body cycling, has been attributed to confining group III and IV skeletal muscle afferent feedback to a small muscle mass, enabling the central nervous system (CNS) to tolerate greater peripheral fatigue. However, as task specificity and vastly differing systemic challenges may have complicated this interpretation, eight males were studied during constant workload trials to exhaustion at 85% of peak workload during single-leg and double-leg KE. It was hypothesized that because of the smaller muscle mass engaged during single-leg KE, a greater magnitude of peripheral quadriceps fatigue would be present at exhaustion. Vastus lateralis integrated electromyogram (iEMG) signal relative to the first minute of exercise, preexercise to postexercise maximal voluntary contractions (MVCs) of the quadriceps, and twitch-force evoked by supramaximal magnetic femoral nerve stimulation (Qtw,pot) quantified peripheral quadriceps fatigue. Trials performed with single-leg KE (8.1 ± 1.2 min; 45 ± 4 W) resulted in significantly greater peripheral quadriceps fatigue than double-leg KE (10 ± 1.3 min; 83 ± 7 W), as documented by changes in the iEMG signal (147 ± 24 vs. 85 ± 13%), MVC (−25 ± 3 vs. −12 ± 3%), and Qtw,pot (−44 ± 6 vs. −33 ± 7%), for single-leg and double-leg KE, respectively. Therefore, avoiding concerns over task specificity and cardiorespiratory limitations, this study reveals that a reduction in muscle mass permits the development of greater peripheral muscle fatigue and supports the concept that the CNS tolerates a greater magnitude of peripheral fatigue when the source of group III/IV afferent feedback is limited to a small muscle mass.
Active removal of inorganic phosphate from cerebrospinal fluid by the choroid plexus
Authors: Guerreiro Pedro M. , Bataille Amy M. , Parker Sonda L. , Renfro J. Larry
Published: April 2014

The Piconcentration of mammalian cerebrospinal fluid (CSF) is about one-half that of plasma, a phenomenon also shown here in the spiny dogfish, Squalus acanthias. The objective of the present study was to characterize the possible role of the choroid plexus (CP) in determining CSF Piconcentration. The large sheet-like fourth CP of the shark was mounted in Ussing chambers where unidirectional33Pifluxes revealed potent active transport from CSF to the blood side under short-circuited conditions. The flux ratio was 8:1 with an average transepithelial resistance of 87 ± 17.9 Ω·cm2and electrical potential difference of +0.9 ± 0.17 mV (CSF side positive). Active Piabsorption from CSF was inhibited by 10 mM arsenate, 0.2 mM ouabain, Na+-free medium, and increasing the K+concentration from 5 to 100 mM. Li+stimulated transport twofold compared with Na+-free medium. Phosphonoformic acid (1 mM) had no effect on active Pitransport. RT-PCR revealed both Pitransporter (PiT)1 and PiT2 (SLC20 family) gene expression, but no Na+-Picotransporter II (SLC34 family) expression, in the shark CP. PiT2 immunoreactivity was shown by immunoblot analysis and localized by immunohistochemistry in (or near) the CP apical microvillar membranes of both the shark and rat. PiT1 appeared to be localized primarily to vascular endothelial cells. Taken together, these data indicate that the CP actively removes Pifrom CSF. This process has transport properties consistent with a PiT2, Na+-dependent transporter that is located in the apical region of the CP epithelium.
COX-2 mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla
Authors: Wang Fei , Lu Xiaohan , Peng Kexin , Zhou Li , Li Chunling , Wang Weidong , Yu Xueqing , Kohan Donald E. , Zhu Shu-Feng , Yang Tianxin
Published: April 2014

(Pro)renin receptor (PRR) is predominantly expressed in the distal nephron where it is activated by angiotensin II (ANG II), resulting in increased renin activity in the renal medulla thereby amplifying the de novo generation and action of local ANG II. The goal of the present study was to test the role of cycloxygenase-2 (COX-2) in meditating ANG II-induced PRR expression in the renal medulla in vitro and in vivo. Exposure of primary rat inner medullary collecting duct cells to ANG II induced sequential increases in COX-2 and PRR protein expression. When the cells were pretreated with a COX-2 inhibitor NS-398, ANG II-induced upregulation of PRR protein expression was almost completely abolished, in parallel with the changes in medium active renin content. The inhibitory effect of NS-398 on the PRR expression was reversed by adding exogenous PGE2. A 14-day ANG II infusion elevated renal medullary PRR expression and active and total renin content in parallel with increased urinary renin, all of which were remarkably suppressed by the COX-2 inhibitor celecoxib. In contrast, plasma and renal cortical active and total renin content were suppressed by ANG II treatment, an effect that was unaffected by COX-2 inhibition. Systolic blood pressure was elevated with ANG II infusion, which was attenuated by the COX-2 inhibition. Overall, the results obtained from in vitro and in vivo studies established a crucial role of COX-2 in mediating upregulation of renal medullary PRR expression and renin content during ANG II hypertension.
Hemodialysis restored iron distribution that was sequestered in the spleen by bilateral nephrectomy
Authors: Kida Aritoshi , Kuragano Takahiro , Furuta Minoru , Otaki Yoshinaga , Hasuike Yukiko , Matsuda Saori , Akaike Nobuhide , Kokuba Yukifumi , Nakanishi Takeshi
Published: April 2014

Acute kidney injury (AKI) is associated with dysregulated iron metabolism, which may play a significant role in cellular injury. The effect of hemodialysis (HD) on iron metabolism in AKI therapy has not been well defined. The effects of HD on iron parameters were tested in control rats and bilateral nephrectomy (BNx) rats. The BNx rats were divided into the following three groups: 1) the sham-operated group (BNx-Sham), 2) the BNx group, and 3) the HD group (BNx-HD), which received HD therapy 40–45 h after BNx. Sections of the liver or spleen were stained with Berlin blue to examine the accumulation of iron. The mRNA levels of hepcidin and ferroportin 1 in the spleen and liver were also quantified using RT-PCR. In the BNx group, the plasma iron and hematocrit levels were decreased, and hepcidin levels were increased. The iron staining in the spleen in the BNx group was significantly more intense than that in the BNx-Sham group; however, after an HD session, splenic iron staining diminished to the level of the sham group along with an increase in plasma iron and a decrease in hepcidin. BNx moved iron from hemoglobin and the plasma to the spleen, which is associated with an increase in plasma hepcidin. A single HD session accelerated the release of iron from the spleen, and the increased plasma iron was linked to the removal of hepcidin. Our data suggested that hepcidin might dynamically modulate the iron metabolism in BNx as well as in HD.
Endogenous release of 5-HT modulates the plateau phase of NMDA-induced membrane potential oscillations in lamprey spinal neurons
Authors: Wang Di , Grillner Sten , Wallén Peter
Published: April 2014

The lamprey central nervous system has been used extensively as a model system for investigating the networks underlying vertebrate motor behavior. The locomotor networks can be activated by application of glutamate agonists, such as N-methyl-D-aspartic acid (NMDA), to the isolated spinal cord preparation. Many spinal neurons are capable of generating pacemaker-like membrane potential oscillations upon activation of NMDA receptors. These oscillations rely on the voltage-dependent properties of NMDA receptors in interaction with voltage-dependent potassium and calcium-dependent potassium (KCa) channels, as well as low voltage-activated calcium channels. Upon membrane depolarization, influx of calcium will activate KCachannels, which in turn, will contribute to repolarization and termination of the depolarized phase. The appearance of the NMDA-induced oscillations varies markedly between spinal cord preparations; they may either have a pronounced, depolarized plateau phase or be characterized by a short-lasting depolarization lasting approximately 200–300 ms without a plateau. Both types of oscillations increase in frequency with increased concentrations of NMDA. Here, we characterize these two types of membrane potential oscillations and show that they depend on the level of endogenous release of 5-HT in the spinal cord preparations. In the lamprey, 5-HT acts to block voltage-dependent calcium channels and will thereby modulate the activity of KCachannels. When 5-HT antagonists were administered, the plateau-like oscillations were converted to the second type of oscillations lacking a plateau phase. Conversely, plateau-like oscillations can be induced or prolonged by 5-HT agonists. These properties are most likely of significance for the modulatory action of 5-HT on the spinal networks for locomotion.
A potentially novel nicotinic receptor inAplysianeuroendocrine cells
Authors: White Sean H. , Carter Christopher J. , Magoski Neil S.
Published: April 2014

Nicotinic receptors form a diverse group of ligand-gated ionotropic receptors with roles in both synaptic transmission and the control of excitability. In the bag cell neurons of Aplysia, acetylcholine activates an ionotropic receptor, which passes inward current to produce a long-lasting afterdischarge and hormone release, leading to reproduction. While testing the agonist profile of the cholinergic response, we observed a second current that appeared to be gated only by nicotine and not acetylcholine. The peak nicotine-evoked current was markedly smaller in magnitude than the acetylcholine-induced current, cooperative (Hill value of 2.7), had an EC50near 500 μM, readily recovered from desensitization, showed Ca2+permeability, and was blocked by mecamylamine, dihydro-β-erythroidine, or strychnine, but not by α-conotoxin ImI, methyllycaconitine, or hexamethonium. Aplysia transcriptome analysis followed by PCR yielded 20 full-length potential nicotinic receptor subunits. Sixteen of these were predicted to be cation selective, and real-time PCR suggested that 15 of the 16 subunits were expressed to varying degrees in the bag cell neurons. The acetylcholine-induced current, but not the nicotine current, was reduced by double-strand RNA treatment targeted to both subunits ApAChR-C and -E. Conversely, the nicotine-evoked current, but not the acetylcholine current, was lessened by targeting both subunits ApAChR-H and -P. To the best of our knowledge, this is the first report suggesting that a nicotinic receptor is not gated by acetylcholine. Separate receptors may serve as a means to differentially trigger plasticity or safeguard propagation by assuring that only acetylcholine, the endogenous agonist, initiates large enough responses to trigger reproduction.
Role of99mTc-ECD SPECT in the Management of Children with Craniosynostosis
Authors: Barik Mayadhar , Bajpai Minu , Das Rashmi Ranajn , Malhotra Arun , Panda Shasanka Shekhar , Sahoo Manas Kumar , Dwivedi Sadanand
Published: April 2014

Purpose of the Report. There is a paucity of data on correlation of various imaging modalities with clinical findings in craniosynostosis. Moreover, no study has specifically reported the role ofTc99m-ECD SPECT in a large number of subjects with craniosynostosis.Materials and Methods. We prospectively analyzed a cohort of 85 patients with craniosynostosis from year 2007 to 2012. All patients underwent evaluation withTc99m-ECD SPECT and the results were correlated with radiological and surgical findings.Results.Tc99m-ECD SPECT revealed regional perfusion abnormalities in the cerebral hemisphere corresponding to the fused sutures preoperatively that disappeared postoperatively in all the cases. Corresponding to this, the mean mental performance quotient (MPQ) increased significantlyP<0.05postoperatively only in those children with absent perfusion defect postoperatively.Conclusions. Our study suggests that early surgery and release of craniosynostosis in patients with preoperative perfusion defects (absent onTc99m-ECD SPECT study) are beneficial, as theylead to improved MPQ after surgery.
Experimental and Numerical Study on Tensile Strength of Concrete under Different Strain Rates
Authors: Min Fanlu , Yao Zhanhu , Jiang Teng
Published: April 2014

The dynamic characterization of concrete is fundamental to understand the material behavior in case of heavy earthquakes and dynamic events. The implementation of material constitutive law is of capital importance for the numerical simulation of the dynamic processes as those caused by earthquakes. Splitting tensile concrete specimens were tested at strain rates of 10−7 s−1to 10−4 s−1in an MTS material test machine. Results of tensile strength versus strain rate are presented and compared with compressive strength and existing models at similar strain rates. Dynamic increase factor versus strain rate curves for tensile strength were also evaluated and discussed. The same tensile data are compared with strength data using a thermodynamic model. Results of the tests show a significant strain rate sensitive behavior, exhibiting dynamic tensile strength increasing with strain rate. In the quasistatic strain rate regime, the existing models often underestimate the experimental results. The thermodynamic theory for the splitting tensile strength of concrete satisfactorily describes the experimental findings of strength as effect of strain rates.
Small Islets Transplantation Superiority to Large Ones: Implications from Islet Microcirculation and Revascularization
Authors: Li Wenjuan , Zhao Ruxing , Liu Jidong , Tian Meng , Lu Yiran , He Tianyi , Cheng Meng , Liang Kai , Li Xia , Wang Xiangdong , Sun Yu , Chen Li
Published: April 2014

Pancreatic islet transplantation is a promising therapy to regain glycemic control in diabetic patients. The selection of ideal grafts is the basis to guarantee short-term effectivity and longevity of the transplanted islets. Contradictory to the traditional notion, recent findings implied the superiority of small islets for better transplantation outcomes rather than the large and intact ones. However, the mechanisms remain to be elucidated. Recent evidences emphasized the major impact of microcirculation on isletβ-cell mass and function. And potentials in islet graft revascularization are crucial for their survival and preserved function in the recipient. In this study, we verified the distinct histological phenotype and functionality of small islets versus large ones both in vitro and in vivo. With efforts to exploring the differences in microcirculation and revascularization of islet grafts, we further evaluated local expressions of angiotensin and vascular endothelial growth factor A (VEGF-A) at different levels. Our findings reveal that, apart from the higher density of insulin-producingβ-cells, small islets express less angiotensin and more angiotrophic VEGF-A. We therefore hypothesized a logical explanation of the small islet superiority for transplantation outcome from the aspects of facilitated microcirculation and revascularization intrinsically in small islets.
Investigation of Anti-Toxocaraand Anti-ToxoplasmaAntibodies in Patients with Schizophrenia Disorder
Authors: Khademvatan Shahram , Khajeddin Niloufar , Izadi Sakineh , Yousefi Elham
Published: April 2014

Objective. The aim of the present study was to examine the relationship betweenToxoplasma gondiiandToxocaraspp. infections in patients with schizophrenia disorder.Method. A total of 100 patients with schizophrenia disorder and 95 healthy individuals participated in the study. Participants were tested for the presence of anti-T. gondiiand anti-Toxocaraspp. antibodies by ELISA and Western blotting. Data were analyzed using Chi-square test and Fisher9s exact test.Results. There were no differences inT. gondiiIgG seroprevalence between patients with schizophrenia and healthy individuals (P=0.1), but there were differences in seroprevalence between males and females with schizophrenia (P=0.009). In contrast,Toxocaraspp. IgG seroprevalence was greater in patients with schizophrenia disorder than in healthy individuals (P=0.02), but there were no differences in seroprevalence between men and women with schizophrenia (P=0.5). Finally, there were no differences in seroprevalence ofT. gondiiorToxocaraspp. IgG among different subtypes of schizophrenia, various age groups, residential area, or clinical course of treatment (P>0.05).Conclusion. The present study suggests that patients with schizophrenia disorder are at elevated risk ofToxocaraspp. infection. Moreover, contamination withT. gondiiis a risk factor for schizophrenia in women.
A Knowledge-Driven Approach to Extract Disease-Related Biomarkers from the Literature
Authors: Bravo À. , Cases M. , Queralt-Rosinach N. , Sanz F. , Furlong L. I.
Published: April 2014

The biomedical literature represents a rich source of biomarker information. However, both the size of literature databases and their lack of standardization hamper the automatic exploitation of the information contained in these resources. Text mining approaches have proven to be useful for the exploitation of information contained in the scientific publications. Here, we show that a knowledge-driven text mining approach can exploit a large literature database to extract a dataset of biomarkers related to diseases covering all therapeutic areas. Our methodology takes advantage of the annotation of MEDLINE publications pertaining to biomarkers with MeSH terms, narrowing the search to specific publications and, therefore, minimizing the false positive ratio. It is based on a dictionary-based named entity recognition system and a relation extraction module. The application of this methodology resulted in the identification of 131,012 disease-biomarker associations between 2,803 genes and 2,751 diseases, and represents a valuable knowledge base for those interested in disease-related biomarkers. Additionally, we present a bibliometric analysis of the journals reporting biomarker related information during the last 40 years.
Optimized Scheduling Technique of Null Subcarriers for Peak Power Control in 3GPP LTE Downlink
Authors: Cho Soobum , Park Sang Kyu
Published: April 2014

Orthogonal frequency division multiple access (OFDMA) is a key multiple access technique for the long term evolution (LTE) downlink. However, high peak-to-average power ratio (PAPR) can cause the degradation of power efficiency. The well-known PAPR reduction technique, dummy sequence insertion (DSI), can be a realistic solution because of its structural simplicity. However, the large usage of subcarriers for the dummy sequences may decrease the transmitted data rate in the DSI scheme. In this paper, a novel DSI scheme is applied to the LTE system. Firstly, we obtain the null subcarriers in single-input single-output (SISO) and multiple-input multiple-output (MIMO) systems, respectively; then, optimized dummy sequences are inserted into the obtained null subcarrier. Simulation results show that Walsh-Hadamard transform (WHT) sequence is the best for the dummy sequence and the ratio of 16 to 20 for the WHT and randomly generated sequences has the maximum PAPR reduction performance. The number of near optimal iteration is derived to prevent exhausted iterations. It is also shown that there is no bit error rate (BER) degradation with the proposed technique in LTE downlink system.
Performance Improvements of Selective Emitters by Laser Openings on Large-Area Multicrystalline Si Solar Cells
Authors: Wang Sheng-Shih , Ho Jyh-Jier , Liou Jia-Jhe , Ho Jia-Show , Hsu Wei-Chih , Lu Wen-Haw , Tsai Song-Yeu , Hung Hsien-Seng , Wang Kang L.
Published: April 2014

This study focuses on the laser opening technique used to form a selective emitter (SE) structure on multicrystalline silicon (mc-Si). This technique can be used in the large-area (156 × 156 mm2) solar cells. SE process of this investigation was performed using 3 samples SE1–SE3. Laser fluences can vary in range of 2–5 J/cm2. The optimal conversion efficiency of 15.95% is obtained with the SE3 (2 J/cm2fluence) after laser opening with optimization of heavy and light dopant, which yields a gain of0.48%abscompared with that of a reference cell (without fluence). In addition, this optimal SE3 cell displays improved characteristics compared with other cells with a higher average value of external quantum efficiency (EQEavg = 68.6%) and a lower average value of power loss (Ploss = 2.33 mW/cm2). For the fabrication of solar cells, the laser opening process comprises fewer steps than traditional photolithography does. Furthermore, the laser opening process decreases consumption of chemical materials; therefore, the laser opening process decreases both time and cost. Therefore, SE process is simple, cheap, and suitable for commercialization. Moreover, the prominent features of the process render it effective means to promote overall performance in the photovoltaic industry.
Cormic Index Profile of Children with Sickle Cell Anaemia in Lagos, Nigeria
Authors: Akodu Samuel Olufemi , Njokanma Olisamedua Fidelis , Kehinde Omolara Adeolu
Published: April 2014

Background. Sickle cell disorders are known to have a negative effect on linear growth. This could potentially affect proportional growth and, hence, Cormic Index.Objective. To determine the Cormic Index in the sickle cell anaemia population in Lagos.Methodology. A consecutive sample of 100 children with haemoglobin genotype SS, aged eight months to 15 years, and 100 age and sex matched controls (haemoglobin genotype AA) was studied. Sitting height (upper segment) and full length or height were measured. Sitting height was then expressed as a percentage of full length/height (Cormic Index).Results. The mean Cormic Index decreased with age among primary subjects (SS) and AA controls. The overall mean Cormic Index among primary subjects was comparable to that of controls (55.0±4.6% versus54.5±5.2%;54.8±4.5% versus53.6±4.9%) in boys and girls, respectively. In comparison with AA controls, female children with sickle cell anaemia who were older than 10 years had a significantly lower mean Cormic Index.Conclusion. There was a significant negative relationship between Cormic Index and height in subjects and controls irrespective of gender. Similarly, a significant negative correlation existed between age, sitting height, subischial leg length, weight, and Cormic Index in both subjects and controls.
Representation of the Solutions of Linear Discrete Systems with Constant Coefficients and Two Delays
Authors: Diblík Josef , Morávková Blanka
Published: April 2014

The purpose of this paper is to develop a method for the construction of solutions to initial problems of linear discrete systems with constant coefficients and with two delaysΔx(k)=Bx(k-m)+Cx(k-n)+f(k),wherem,n∈ℕ,m≠n,are fixed,k=0,…,∞,B=(bij),C=(cij)are constantr×rmatrices,fis a givenr×1vector, andxis anr×1unknown vector. Solutions are expressed with the aid of a special function called the discrete matrix delayed exponential for two delays. Such approach results in a possibility to express an initial Cauchy problem in a closed form. Examples are shown illustrating the results obtained.
End-Completely-Regular and End-Inverse Lexicographic Products of Graphs
Authors: Hou Hailong , Gu Rui
Published: April 2014

A graphXis said to be End-completely-regular (resp., End-inverse) if its endomorphism monoid End(X) is completely regular (resp., inverse). In this paper, we will show that ifX[Y] is End-completely-regular (resp., End-inverse), then bothXandYare End-completely-regular (resp., End-inverse). We give several approaches to construct new End-completely-regular graphs by means of the lexicographic products of two graphs with certain conditions. In particular, we determine the End-completely-regular and End-inverse lexicographic products of bipartite graphs.
Design of a 2 GHz Linear-in-dB Variable-Gain Amplifier with 80-dB Gain Range
Authors: Sun Zhengyu , Yan Yuepeng
Published: April 2014

A broadband linear-in-dB variable-gain amplifier (VGA) circuit is implemented in 0.18 μm SiGe BiCMOS process. The VGA comprises two cascaded variable-gain core, in which a hybrid current-steering current gain cell is inserted in the Cherry-Hooper amplifier to maintain a broad bandwidth while covering a wide gain range. Postlayout simulation results confirm that the proposed circuit achieves a 2 GHz 3-dB bandwidth with wide linear-in-dB gain tuning range from −19 dB up to 61 dB. The amplifier offers a competitive gain bandwidth product of 2805 GHz at the maximum gain for a 110-GHz ftBiCMOS technology. The amplifier core consumes 31 mW from a 3.3 V supply and occupies active area of 280 μm by 140 μm.
The Preparation and Performances of Self-Dispersed Nanomicron Emulsified Wax Solid Lubricant Ewax for Drilling Fluids
Authors: Zhou Feng-shan , Wang Ting-ting , Xiong Zheng-qiang , Guo Wen-yue , Xiang Xi , Wang Huan-na , Zhu Xia-lei , Liu Fang , Cui Bao-lin
Published: April 2014

An oil-in-water nanomicron wax emulsion with oil phase content 45 wt% was prepared by using the emulsifying method of surfactant-in-oil. The optimum prepared condition is 85°C, 20 min, and 5 wt% complex emulsifiers. Then the abovementioned nanomicron emulsifying wax was immersed into a special water-soluble polymer in a certain percentage by the semidry technology. At last, a solidified self-dispersed nanomicron emulsified wax named as Ewax, a kind of solid lubricant for water based drilling fluid, was obtained after dried in the special soluble polymer containing emulsifying wax in low temperature. It is shown that the adhesion coefficient reduced rate(ΔKf)is 73.5% and the extreme pressure (E-P) friction coefficient reduced rate(Δf)is 77.6% when the produced Ewax sample was added to fresh water based drilling fluid at dosage 1.0 wt%. In comparison with other normal similar liquid products, Ewax not only has better performances of lubrication, filtration loss control property, heat resistance, and tolerance to salt and is environmentally friendly, but also can solve the problems of freezing in the winter and poor storage stability of liquid wax emulsion in oilfield applications.
Physical Exercise Reduces the Expression of RANTES and Its CCR5 Receptor in the Adipose Tissue of Obese Humans
Authors: Baturcam Engin , Abubaker Jehad , Tiss Ali , Abu-Farha Mohamed , Khadir Abdelkrim , Al-Ghimlas Fahad , Al-Khairi Irina , Cherian Preethi , Elkum Naser , Hammad Maha , John Jeena , Kavalakatt Sina , Lehe Cynthia , Warsame Samia , Behbehani Kazem , Dermime Said , Dehbi Mohammed
Published: April 2014

RANTES and its CCR5 receptor trigger inflammation and its progression to insulin resistance in obese. In the present study, we investigated for the first time the effect of physical exercise on the expression of RANTES and CCR5 in obese humans. Fifty-seven adult nondiabetic subjects (17 lean and 40 obese) were enrolled in a 3-month supervised physical exercise. RANTES and CCR5 expressions were measured in PBMCs and subcutaneous adipose tissue before and after exercise. Circulating plasma levels of RANTES were also investigated. There was a significant increase in RANTES and CCR5 expression in the subcutaneous adipose tissue of obese compared to lean. In PBMCs, however, while the levels of RANTES mRNA and protein were comparable between both groups, CCR5 mRNA was downregulated in obese subjects (P<0.05). Physical exercise significantly reduced the expression of both RANTES and CCR5 (P<0.05) in the adipose tissue of obese individuals with a concomitant decrease in the levels of the inflammatory markers TNF-α, IL-6, and P-JNK. Circulating RANTES correlated negatively with anti-inflammatory IL-1ra (P=0.001) and positively with proinflammatory IP-10 and TBARS levels (P<0.05). Therefore, physical exercise may provide an effective approach for combating the deleterious effects associated with obesity through RANTES signaling in the adipose tissue.
Plastic Changes in the Spinal Cord in Motor Neuron Disease
Authors: Fornai Francesco , Ferrucci Michela , Lenzi Paola , Falleni Alessandra , Biagioni Francesca , Flaibani Marina , Siciliano Gabriele , Giannessi Francesco , Paparelli Antonio
Published: April 2014

In the present paper, we analyze the cell number within lamina X at the end stage of disease in a G93A mouse model of ALS; the effects induced by lithium; the stem-cell like phenotype of lamina X cells during ALS; the differentiation of these cells towards either a glial or neuronal phenotype. In summary we found that G93A mouse model of ALS produces an increase in lamina X cells which is further augmented by lithium administration. In the absence of lithium these nestin positive stem-like cells preferentially differentiate into glia (GFAP positive), while in the presence of lithium these cells differentiate towards a neuron-like phenotype (βIII-tubulin, NeuN, and calbindin-D28K positive). These effects of lithium are observed concomitantly with attenuation in disease progression and are reminiscent of neurogenetic effects induced by lithium in the subependymal ventricular zone of the hippocampus.
Stability Analysis of a Multigroup SEIR Epidemic Model with General Latency Distributions
Authors: Wang Nan , Pang Jingmei , Wang Jinliang
Published: April 2014

The global stability of a multigroup SEIR epidemic model with general latency distribution and general incidence rate is investigated. Under the given assumptions, the basic reproduction numberℜ0is defined and proved as the role of a threshold; that is, the disease-free equilibriumP0is globally asymptotically stable ifℜ0≤1, while an endemic equilibriumP*exists uniquely and is globally asymptotically stable ifℜ0>1. For the proofs, we apply the classical method of Lyapunov functionals and a recently developed graph-theoretic approach.
On Fuzzy Ideals ofBL-Algebras
Authors: Meng Biao Long , Xin Xiao Long
Published: April 2014

In this paper we investigate further properties of fuzzy ideals of aBL-algebra. The notions of fuzzy prime ideals, fuzzy irreducible ideals, and fuzzy Gödel ideals of aBL-algebra are introduced and their several properties are investigated. We give a procedure to generate a fuzzy ideal by a fuzzy set. We prove that every fuzzy irreducible ideal is a fuzzy prime ideal but a fuzzy prime ideal may not be a fuzzy irreducible ideal and prove that a fuzzy prime idealωis a fuzzy irreducible ideal if and only ifω0=1and|Im⁡(ω)|=2. We give the Krull-Stone representation theorem of fuzzy ideals inBL-algebras. Furthermore, we prove that the lattice of all fuzzy ideals of aBL-algebra is a complete distributive lattice. Finally, it is proved that every fuzzy Boolean ideal is a fuzzy Gödel ideal, but the converse implication is not true.
In Search of the Active Metabolites of an Anticancer Piperazinedione, TW01003, in Rats
Authors: Wang Chun-Li , Chen Ching-Kuei , Wang Yao-Horng , Cheng Yu-Wen
Published: April 2014

TW01003, a piperazinedione derivative designed as an antimitotic agent, exhibited potent anticancer and antiangiogenesis activities in mice. However, oral administration of this compound in rats led to poor systemic bioavailability which suggested thatin vivoefficacy might come from its metabolites. This report describes the identification of TW01003 metabolites in pig and Wistar rats. Following intravenous administration of TW01003, pig urine samples were subjected to sulfatase and glucuronidase treatment to monitor the biotransformation products. Rats were given TW01003 both intravenously and orally, and blood samples were collected and then analyzed by HPLC to quantitatively determine the metabolic transformation of TW01003 to its metabolite. A sulfate conjugate, TW01003 sulfate, was identified as the major metabolite for TW01003 after intravenous injection in both pig and rats. However, in rats, the glucuronide conjugate became major metabolite 30 min after TW01003 oral dosing. Pharmacokinetic analysis after intravenous administration of TW01003 indicated that TW01003 sulfate had a systemic bioavailability 2.5 times higher, volume of distribution three times higher, residence time seven times longer, and clearance rate 2.3 times lower compared to TW01003. Our results indicate that the potent anticancer and antiangiogenesis activities of TW01003 might not come from TW01003per sebut from its metabolites TW01003 sulfate.
Hydrogen Gas Presents a Promising Therapeutic Strategy for Sepsis
Authors: Xie Keliang , Liu Lingling , Yu Yonghao , Wang Guolin
Published: April 2014

Sepsis is characterized by a severe inflammatory response to infection. It remains a major cause of morbidity and mortality in critically ill patients despite developments in monitoring devices, diagnostic tools, and new therapeutic options. Recently, some studies have found that molecular hydrogen is a new therapeutic gas. Our studies have found that hydrogen gas can improve the survival and organ damage in mice and rats with cecal ligation and puncture, zymosan, and lipopolysaccharide-induced sepsis. The mechanisms are associated with the regulation of oxidative stress, inflammatory response, and apoptosis, which might be through NF-κB and Nrf2/HO-1 signaling pathway. In this paper, we summarized the progress of hydrogen treatment in sepsis.
A Comparison of Nicotine Biomarkers and Smoking Patterns in Daily and Nondaily Smokers
Authors: Shiffman Saul , Dunbar Michael S. , Benowitz Neal L.
Published: April 2014

Background: Nondaily or intermittent smokers (ITS) are increasingly common, but how much nicotine, if any, ITS take in and how quickly they metabolize it has not yet been studied.

Methods: We compared carbon monoxide (CO), urinary cotinine, and nicotine metabolism [nicotine metabolite ratio (NMR): 3-hydroxycotinine:cotinine] in 224 ITS and 222 daily smokers (DS). Effects of gender and ethnicity were examined.

Results: DS had higher cotinine concentrations than ITS (1,396 ± 69 vs. 478 ± 44 ng/mL), attributable to higher cigarettes per day (CPD). In both groups, cotinine rose more slowly as CPD increased. There were no differences in cotinine between White (WH) and African American (AA) DS; among ITS, AA cotinine was over twice that of WH. Among DS, CO was significantly higher among WH than AA smokers, but significantly lower among WH ITS than AA ITS. Although AA ITS smoked more than WH ITS (CPD: 4.13 ± 0.55 vs. 3.31 ± 0.41), this did not account for the observed cotinine nor CO differences. There were no differences in NMR by group or race, nor any gender effects.

Conclusions: At comparable CPD, DS' and ITS' intake of nicotine per cigarette was similar, as were their rates of nicotine metabolism. Among ITS, AA smokers smoke more and take in more nicotine per cigarette than WH ITS, consistent with the view of ITS as a heterogeneous group.

Impact: Differences in nicotine intake per cigarette and metabolism likely cannot account for differences in DS and ITS smoking. Future studies should explore ethnic differences in ITS smoking. Cancer Epidemiol Biomarkers Prev; 23(7); 1264–72. ©2014 AACR.
Evaluation of Apoptosis Induction by Concomitant Inhibition of MEK, mTOR, and Bcl-2 in Human Acute Myelogenous Leukemia Cells
Authors: Zhang Weiguo , Ruvolo Vivian R. , Gao Chen , Zhou Liran , Bornmann William , Tsao Twee , Schober Wendy D. , Smith Paul , Guichard Sylvie , Konopleva Marina , Andreeff Michael
Published: April 2014

Aberrant activation of multiple signaling pathways is common in acute myelogenous leukemia (AML) cells, which can be linked to a poor prognosis for patients with this disease. Previous research with mTOR or MEK inhibitors revealed cytostatic, rather than cytotoxic, effects in in vitro and in vivo AML models. We evaluated the combination effect of the mTOR inhibitor AZD8055 and the MEK inhibitor selumetinib on human AML cell lines and primary AML samples. This combination demonstrated synergistic proapoptotic effects in AML cells with high basal activation of MEK and mTOR. We next incorporated the BH3 mimetic ABT-737 into this combination regimen to block Bcl-2, which further enhanced the apoptogenic effect of MEK/mTOR inhibition. The combination treatment also had a striking proapoptotic effect in CD33+/CD34+ AML progenitor cells from primary AML samples with NRAS mutations. Mechanistically, upregulation of the proapoptotic protein Bim, accompanied by the downregulation of the antiapoptotic protein Mcl-1 (mainly via protein degradation), seemed to play critical roles in enhancing the combination drug effect. Furthermore, the modulation of survivin, Bax, Puma, and X-chromosome-linked inhibitor of apoptosis protein (XIAP) expression suggested a role for mitochondria-mediated apoptosis in the cytotoxicity of the drug combination. Consequently, the concomitant blockade of prosurvival MEK/mTOR signaling and the deactivation of Bcl-2 could provide a mechanism-based integrated therapeutic strategy for the eradication of AML cells. Mol Cancer Ther; 13(7); 1848–59. ©2014 AACR.
ABT-737 Promotes the Dislocation of ER Luminal Proteins to the Cytosol, Including Pseudomonas Exotoxin
Authors: Antignani Antonella , Sarnovsky Robert , FitzGerald David J.
Published: April 2014

Impaired apoptosis is often a key element in tumor development. Therefore, drugs mimicking prosurvival antagonists offer promise as cancer therapeutics. When ABT-737, a BH3-only mimetic, was added to KB3-1 human cervical adenocarcinoma cells, we noted an induction of an endoplasmic reticulum (ER) stress response and the dislocation of ER luminal proteins, including chaperones, to the cell cytosol. Furthermore, when immunotoxin (antibody–toxin chimeric molecule) and ABT-737 combinations were added to cells, there was enhanced toxin-mediated inhibition of protein synthesis, consistent with enhanced translocation of toxin to the cytosol. A similar enhancement was not seen with thapsigargin, suggesting that ER stress alone was not responsible for enhanced translocation. Cytosol preparations from ABT-737–treated but not from thapsigargin-treated cells revealed the presence of greater amounts of processed 37-kDa toxin fragment compared with the addition of immunotoxin alone. As early as 4 hours after the addition of ABT-737 and immunotoxin, there was release of mitochondrial cytochrome c and activation of caspase-3/7 indicating that the combination caused apoptotic cell death. These results were reflected in decreased cellular ATP levels that were noted with combinations of ABT-737 and immunotoxin but not with either agent alone or with combinations of thapsigargin and immunotoxin. We conclude that ABT-737 increases ER permeability, promoting the dislocation of toxin from the ER to the cytosol resulting in early apoptotic cell death. These mechanistic insights suggest why this class of BH3-only mimetic synergizes in a particular way with Pseudomonas exotoxin–based immunotoxins. Mol Cancer Ther; 13(6); 1655–63. ©2014 AACR.
Therapeutic Benefits in Atopic Dermatitis Care from the Patients' Perspective: Results of the German National Health Care Study ‘Atopic Health'
Authors: Steinke Sabine , Langenbruch Anna , Ständer Sonja , Franzke Nadine , Augustin Matthias
Published: April 2014

Background/Aims: Numerous therapies are recommended to treat atopic dermatitis. The German national health care study ‘Atopic Health' generated nationwide data on the care situation from the patients' perspective. Methods: Data for 1,678 adult patients were collected within a retrospective cohort study throughout the year 2010. Six scores to capture satisfaction with care, quality of life (Dermatology Life Quality Index, EQ-5D-VAS), therapeutic success and benefits (Patient Benefit Index) were analyzed using descriptive methods and analysis of variance. Results: 82.1% of patients were highly satisfied with their treatment. Topical corticosteroids and climate therapies were associated with the best success ratings. Quality of life was moderately impaired (mean Dermatology Life Quality Index 8.5 ± 6.5). 88.4% of the patients indicated a relevant therapeutic benefit (Patient Benefit Index ≥1) with significantly better scores for topical immunomodulating therapies and climate therapies. Conclusion: The most frequently applied therapies presented pleasant success and benefit ratings, even if quality of life could be improved for more than one third of patients.
Sudden Death in Incident Dialysis Patients
Authors: Vázquez Eduardo , Sánchez-Perales Carmen , García-García Francisco , García-Cortés M. José , Torres Javier , Borrego Francisco , Salas Daniel , Liébana Antonio , Fernandez-Guerrero Juan Carlos
Published: April 2014

Background: Sudden death (SD) constitutes one of the principal causes of death and is an important problem in healthcare provision. Cardiovascular diseases have a high prevalence in dialysis patients and constitute the principal cause of death. We sought to analyze retrospectively the incidence of SD in patients commencing dialysis and the factors related to its presence. Methods: We evaluated all the patients who began dialysis in our center between 1/11/2003 and 15/9/2007, and who were followed up until death, transplant, or study completion on 31/12/2012. We determined the presence of SD according to the following criteria: SD at 24 h (SD 24H): unexpected death occurring in the 24 h following the start of symptoms, or when the patient was found dead and had been seen alive 24 h earlier; SD at 1 h (SD 1H): death witnessed as occurring in the first hour following the start of symptoms. Results: We evaluated 285 patients, mean age 65.67 ± 15.7 years. In a follow-up of 39.9 ± 34.2 months (947.6 patient-years of follow-up) 168 died (59%), 28 (10%) patients presented SD 24H (2.9/100 patient-years), and 16 (6%) patients presented SD 1H (1.7/100 patient-years). In the multivariate analysis, having had a myocardial infarction or having had electrocardiographic abnormalities (Q wave, negative T wave, subendocardial lesion or QRS >120 ms) were the principal independent predictors of SD 24H (OR 7.83; 95% CI 2.20-27.86; p = 0.001) and of SD 1H (OR 13.43; 95% CI 1.56-115.42; p = 0.018). Conclusions: SD on dialysis is very frequent. Two groups can be identified easily, with risk profiles clearly differentiated.
Whole blood thrombin generation in Bmal1-deficient mice
Authors: Ninivaggi Marisa , Kelchtermans Hilde , Kuijpers Marijke J. , Hemmeryckx Bianca , Heemskerk Johan W. M. , Lindhout Theo , Hoylaerts Marc F. , de Laat Bas
Published: April 2014

The Calibrated Automated Thrombogram (CAT) assay that measures thrombin generation (TG) in platelet-poor and -rich plasma, is increasingly being recognised as a more sensitive tool to determine the overall function of the haemostatic system. We developed a method enabling the measurement of TG in a small aliquot of blood. The objective was to validate this assay in mouse blood and to examine the rate and extent of TG in a mouse model of premature aging. TG was assayed in blood from 20– to 28-week-old brain and muscle ARNT-like protein-1 (Bmal1)-deficient (knockout, KO) mice and wild-type (WT) littermates. Bmal1-KO mice are known to display symptoms of premature aging. TG was initiated by adding calcium, tissue factor and a thrombin specific substrate. After TG, the samples were prepared for scanning electron microscopy (SEM). The intra-assay variations (%) in mouse blood of the endogenous thrombin potential (ETP), peak height, lag time, time-to-peak and velocity index were 10% or less (n=24). We found that Bmal1-KO mice have a significantly (p<0.001) higher ETP (437 ± 7 nM.min; mean ± SD, n=7) when compared with WT mice (ETP=220 ± 45 nM.min; mean ± SD, n=5). The peak heights also differed significantly (p=0.027). By applying SEM we found that Bmal1 deficient mice display a denser fibrin network with smaller pores compared to WT mice. In conclusion, the whole blood TG assay in mice revealed to be reproducible. As a proof-of-principle we have shown that the whole blood TG assay is capable of detecting a prothrombotic phenotype in Bmal1-KO mice.
Oxidative Post-Translational Modifications Develop LONP1 Dysfunction in Pressure Overload Heart Failure
Authors: Hoshino Atsushi , Okawa Yoshifumi , Ariyoshi Makoto , Kaimoto Satoshi , Uchihashi Motoki , Fukai Kuniyoshi , Iwai-Kanai Eri , Matoba Satoaki
Published: April 2014

Background—

Mitochondrial compromise is a fundamental contributor to heart failure. Recent studies have revealed that several surveillance systems maintain mitochondrial integrity. The present study evaluated the role of mitochondrial AAA+ protease in a mouse model of pressure overload heart failure.

Methods and Results—

The fluorescein isothiocyanate casein assay and immunoblotting for endogenous mitochondrial proteins revealed a marked reduction in ATP-dependent proteolytic activity in failing heart mitochondria. The level of reduced cysteine was decreased, and tyrosine nitration and protein carbonylation were promoted in Lon protease homolog (LONP1), the most abundant mitochondrial AAA+ protease, in heart failure. Comprehensive analysis revealed that electron transport chain protein levels were increased even with a reduction in the expression of their corresponding mRNAs in heart failure, which indicated decreased protein turnover and resulted in the accumulation of oxidative damage in the electron transport chain. The induction of mitochondria-targeted human catalase ameliorated proteolytic activity and protein homeostasis in the electron transport chain, leading to improvements in mitochondrial energetics and cardiac contractility even during the late stage of pressure overload. Moreover, the infusion of mitoTEMPO, a mitochondria-targeted superoxide dismutase mimetic, recovered oxidative modifications of LONP1 and improved mitochondrial respiration capacity and cardiac function. The in vivo small interfering RNA repression of LONP1 partially canceled the protective effects of mitochondria-targeted human catalase induction and mitoTEMPO infusion.

Conclusions—

Oxidative post-translational modifications attenuate mitochondrial AAA+ protease activity, which is involved in impaired electron transport chain protein homeostasis, mitochondrial respiration deficiency, and left ventricular contractile dysfunction. Oxidatively inactivated proteases may be an endogenous target for mitoTEMPO treatment in pressure overload heart failure.