bluuebunny/crossref_metadata_2025 huggingface dataset:
An Online Learning Approach to Improving the Quality of Crowd-Sourcing
Authors: Liu Yang , Liu Mingyan
Published: June 2015

We consider a crowd-sourcing problem where in the process of labeling massive datasets, multiple labelers with unknown annotation quality must be selected to perform the labeling task for each incoming data sample or task, with the results aggregated using for example simple or weighted majority voting rule. In this paper we approach this labeler selection problem in an online learning framework, whereby the quality of the labeling outcome by a specific set of labelers is estimated so that the learning algorithm over time learns to use the most effective combinations of labelers. This type of online learning in some sense falls under the family of multi-armed bandit (MAB) problems, but with a distinct feature not commonly seen: since the data is unlabeled to begin with and the labelers' quality is unknown, their labeling outcome (or reward in the MAB context) cannot be directly verified; it can only be estimated against the crowd and known probabilistically. We design an efficient online algorithm LS_OL using a simple majority voting rule that can differentiate high- and low-quality labelers over time, and is shown to have a regret (w.r.t. always using the optimal set of labelers) of O(log
2
T) uniformly in time under mild assumptions on the collective quality of the crowd, thus regret free in the average sense. We discuss performance improvement by using a more sophisticated majority voting rule, and show how to detect and filter out "bad" (dishonest, malicious or very incompetent) labelers to further enhance the quality of crowd-sourcing. Extension to the case when a labeler's quality is task-type dependent is also discussed using techniques from the literature on continuous arms. We present numerical results using both simulation and a real dataset on a set of images labeled by Amazon Mechanic Turks (AMT).
Smartphone Energy Drain in the Wild
Authors: Chen Xiaomeng , Ding Ning , Jindal Abhilash , Hu Y. Charlie , Gupta Maruti , Vannithamby Rath
Published: June 2015

The limited battery life of modern smartphones remains a leading factor adversely affecting the mobile experience of millions of smartphone users. In order to extend battery life, it is critical to understand where and how is energy drain happening on users' phones under normal usage, for example, in a one-day cycle.

In this paper, we conduct the first extensive measurement and modeling of energy drain of 1520 smartphone in the wild. We make two primary contributions. First, we develop a hybrid power model that integrates utilization-based models and FSM-based models for different phone components with a novel technique that estimates the triggers for the FSM-based network power model based on network utilization. Second, through analyzing traces collected on 1520 Galaxy S3 and S4 devices in the wild, we present detailed analysis of where the CPU time and energy are spent across the 1520 devices, inside the 800 apps, as well as along several evolution dimensions, including hardware, Android, cellular, and app updates. Our findings of smartphone energy drain in the wild have significant implications to the various key players of the Android phone eco-system, including phone vendors
Samsung
, Android developers, app developers, and ultimately millions of smartphone users, towards the common goal of extending smartphone battery life and improving the user mobile experience.
Investigating the Potential of the Inter-IXP Multigraph for the Provisioning of Guaranteed End-to-End Services
Authors: Kotronis Vasileios , Klöti Rowan , Rost Matthias , Georgopoulos Panagiotis , Ager Bernhard , Schmid Stefan , Dimitropoulos Xenofontas
Published: June 2015

In this work, we propose utilizing the rich connectivity between IXPs and ISPs for inter-domain path stitching, supervised by centralized QoS brokers. In this context, we highlight a novel abstraction of the Internet topology, i.e., the inter-IXP multigraph composed of IXPs and paths crossing the domains of their shared member ISPs. This can potentially serve as a dense Internet-wide substrate for provisioning guaranteed end-to-end (e2e) services with high path diversity and global IPv4 address space reach. We thus map the IXP multigraph, evaluate its potential, and introduce a rich algorithmic framework for path stitching on such graph structures.
Kraken
Authors: Fuerst Carlo , Schmid Stefan , Suresh Lalith , Costa Paolo
Published: June 2015

It is well-known that without strict network bandwidth guarantees, application performance in multi-tenant cloud environments is unpredictable. While recently proposed systems support explicit bandwidth reservation mechanisms, they require the resource schedules to be announced
ahead of time
. We argue that this is not practical in today's cloud environments, where application demands are inherently unpredictable, e.g., due to stragglers. We in this paper present KRAKEN, a system that allows tenants to dynamically request and
update
minimum resource guarantees for both network bandwidth and compute resources
at runtime
. Unlike previous work, Kraken does not require prior knowledge about the resource needs of the tenants' applications but allows tenants to modify their reservation at runtime. Kraken achieves this through an
online resource reservation scheme
, and by optimally embedding and reconfiguring virtual networks.
Tree-structured Bloom Filters for Joint Optimization of False Positive Probability and Transmission Bandwidth
Authors: Fu Yongquan , Biersack Ernst
Published: June 2015

Bloom filters are frequently used to perform set queries that test the existence of some items. However, Bloom filters face a dilemma: the transmission bandwidth and the accuracy cannot be optimized simultaneously. This dilemma is particularly severe for transmitting Bloom filters to remote nodes when the network bandwidth is limited. We propose a novel Bloom filter
BloomTree
that consists of a tree-structured organization of smaller Bloom filters, each one using a set of independent hash functions. BloomTree spreads items across levels that are compressed to reduce the transmission bandwidth need. We investigate in detail under which conditions BloomTree performs better than the compressed Bloom filter and the standard Bloom filter.
Understanding Parallel Performance Under Interferences in Multi-tenant Clouds
Authors: Zhao Yong , Rao Jia , Zhou Xiaobo , Yi Qing
Published: June 2015

The performance of parallel programs is notoriously difficult to reason in virtualized environments. Although performance degradations caused by virtualization and interferences have been well studied, there is little understanding why different parallel programs have unpredictable slow- downs. We find that unpredictable performance is the result of complex interplays between the design of the program, the memory hierarchy of the hosting system, and the CPU scheduling in the hypervisor. We develop a profiling tool, vProfile, to decompose parallel runtime into three parts: compute, steal and synchronization. With the help of time breakdown, we devise two optimizations at the hypervisor to reduce slowdowns.
Towards Cooling Internet-Scale Distributed Networks on the Cheap
Authors: Gupta Vani , Lee Stephen , Shenoy Prashant , Sitaraman Ramesh , Urgaonkar Rahul
Published: June 2015

Internet-scale Distributed Networks (IDNs) are large distributed systems that comprise hundreds of thousands of servers located around the world. IDNs consume significant amounts of energy to power their deployed server infrastructure, and nearly as much energy to cool that infrastructure. We study the potential benefits of using renewable open air cooling (OAC) in an IDN. Our results show that by using OAC, a global IDN can extract 51% cooling energy reducing during summers and a 92% reduction in the winter.
Potassium channel KCNJ15 is required for histamine-stimulated gastric acid secretion
Authors: Yuan Jianye , Liu Wensheng , Karvar Serhan , Baker Susan S. , He Wenjun , Baker Robert D. , Ji Guang , Xie Jianqun , Zhu Lixin
Published: June 2015

Gastric acid secretion is mediated by the K+-dependent proton pump (H+,K+-ATPase), which requires a continuous supply of K+ at the luminal side of the apical membrane. Several K+ channels are implicated in gastric acid secretion. However, the identity of the K+ channel(s) responsible for apical K+ supply is still elusive. Our previous studies have shown the translocation of KCNJ15 from cytoplasmic vesicles to the apical membrane on stimulation, indicating its involvement in gastric acid secretion. In this study, the stimulation associated trafficking of KCNJ15 was observed in a more native context with a live cell imaging system. KCNJ15 molecules in resting live cells were scattered in cytoplasm but exhibited apical localization after stimulation. Furthermore, knocking down KCNJ15 expression with a short hairpin RNA adenoviral construct abolished histamine-stimulated acid secretion in rabbit primary parietal cells. Moreover, KCNJ15, like H+,K+-ATPase, was detected in all of the parietal cells by immunofluorescence staining, whereas only about half of the parietal cells were positive for KCNQ1 under the same condition. Consistently, the endogenous protein levels of KCNJ15, analyzed by Western blotting, were higher than those of KCNQ1 in the gastric mucosa of human, mouse, and rabbit. These results provide evidence for a major role of KCNJ15 in apical K+ supply during stimulated acid secretion.
Endothelial cell tumor growth is Ape/ref-1 dependent
Authors: Biswas Ayan , Khanna Savita , Roy Sashwati , Pan Xueliang , Sen Chandan K. , Gordillo Gayle M.
Published: June 2015

Tumor-forming endothelial cells have highly elevated levels of Nox-4 that release H2O2 into the nucleus, which is generally not compatible with cell survival. We sought to identify compensatory mechanisms that enable tumor-forming endothelial cells to survive and proliferate under these conditions. Ape-1/ref-1 (Apex-1) is a multifunctional protein that promotes DNA binding of redox-sensitive transcription factors, such as AP-1, and repairs oxidative DNA damage. A validated mouse endothelial cell (EOMA) tumor model was used to demonstrate that Nox-4-derived H2O2 causes DNA oxidation that induces Apex-1 expression. Apex-1 functions as a chaperone to keep transcription factors in a reduced state. In EOMA cells Apex-1 enables AP-1 binding to the monocyte chemoattractant protein-1 ( mcp-1) promoter and expression of that protein is required for endothelial cell tumor formation. Intraperitoneal injection of the small molecule inhibitor E3330, which specifically targets Apex-1 redox-sensitive functions, resulted in a 50% decrease in tumor volume compared with mice injected with vehicle control ( n = 6 per group), indicating that endothelial cell tumor proliferation is dependent on Apex-1 expression. These are the first reported results to establish Nox-4 induction of Apex-1 as a mechanism promoting endothelial cell tumor formation.
Physical and functional interactions between a glioma cation channel and integrin-β1 require α-actinin
Authors: Rooj Arun K. , Liu Zhiyong , McNicholas Carmel M. , Fuller Catherine M.
Published: June 2015

Major plasma membrane components of the tumor cell, ion channels, and integrins play crucial roles in metastasis. Glioma cells express an amiloride-sensitive nonselective cation channel composed of acid-sensing ion channel (ASIC)-1 and epithelial Na+ channel (ENaC) α- and γ-subunits. Inhibition of this channel is associated with reduced cell migration and proliferation. Using the ASIC-1 subunit as a reporter for the channel complex, we found a physical and functional interaction between this channel and integrin-β1. Short hairpin RNA knockdown of integrin-β1 attenuated the amiloride-sensitive current, which was due to loss of surface expression of ASIC-1. In contrast, upregulation of membrane expression of integrin-β1 increased the surface expression of ASIC-1. The link between the amiloride-sensitive channel and integrin-β1 was mediated by α-actinin. Downregulation of α-actinin-1 or -4 attenuated the amiloride-sensitive current. Mutation of the putative binding site for α-actinin on the COOH terminus of ASIC-1 reduced the membrane localization of ASIC-1 and also resulted in attenuation of the amiloride-sensitive current. Our data suggest a novel interaction between the amiloride-sensitive glioma cation channel and integrin-β1, mediated by α-actinin. This interaction may form a mechanism by which channel activity can regulate glioma cell proliferation and migration.
BH3 domain-independent apolipoprotein L1 toxicity rescued by BCL2 prosurvival proteins
Authors: Heneghan J. F. , Vandorpe D. H. , Shmukler B. E. , Giovinazzo J. A. , Raper J. , Friedman D. J. , Pollak M. R. , Alper S. L.
Published: June 2015

The potent trypanolytic properties of human apolipoprotein L1 (APOL1) can be neutralized by the trypanosome variant surface antigen gene product known as serum resistance-associated protein. However, two common APOL1 haplotypes present uniquely in individuals of West African ancestry each encode APOL1 variants resistant to serum resistance-associated protein, and each confers substantial resistance to human African sleeping sickness. In contrast to the dominantly inherited anti-trypanosomal activity of APOL1, recessive inheritance of these two trypanoprotective APOL1 alleles predisposes to kidney disease. Proposed mechanisms of APOL1 toxicity have included BH3 domain-dependent autophagy and/or ion channel activity. We probed these potential mechanisms by expressing APOL1 in Xenopus laevis oocytes. APOL1 expression in oocytes increased ion permeability and caused profound morphological deterioration (toxicity). Coexpression of BCL2 family members rescued APOL1-associated oocyte toxicity in the order MCL1 ∼ BCLW > BCLXL ∼ BCL2A1 ≫ BCL2. Deletion of nine nominal core BH3 domain residues abolished APOL1-associated toxicity, but missense substitution of the same residues abolished neither oocyte toxicity nor its rescue by coexpressed MCL1. The APOL1 BH3 domain was similarly dispensable for the ability of APOL1 to rescue intact mice from lethal trypanosome challenge. Replacement of most extracellular Na+ by K+ also reduced APOL1-associated oocyte toxicity, allowing demonstration of APOL1-associated increases in Ca2+ and Cl− fluxes and oocyte ion currents, which were similarly reduced by MCL1 coexpression. Thus APOL1 toxicity in Xenopus oocytes is BH3-independent, but can nonetheless be rescued by some BCL2 family proteins.
Biomechanical strain induces elastin and collagen production in human pluripotent stem cell-derived vascular smooth muscle cells
Authors: Wanjare Maureen , Agarwal Nayan , Gerecht Sharon
Published: June 2015

Blood vessels are subjected to numerous biomechanical forces that work harmoniously but, when unbalanced because of vascular smooth muscle cell (vSMC) dysfunction, can trigger a wide range of ailments such as cerebrovascular, peripheral artery, and coronary artery diseases. Human pluripotent stem cells (hPSCs) serve as useful therapeutic tools that may help provide insight on the effect that such biomechanical stimuli have on vSMC function and differentiation. In this study, we aimed to examine the effect of biomechanical strain on vSMCs derived from hPSCs. The effects of two types of tensile strain on hPSC-vSMC derivatives at different stages of differentiation were examined. The derivatives included smooth muscle-like cells (SMLCs), mature SMLCs, and contractile vSMCs. All vSMC derivatives aligned perpendicularly to the direction of cyclic uniaxial strain. Serum deprivation and short-term uniaxial strain had a synergistic effect in enhancing collagen type I, fibronectin, and elastin gene expression. Furthermore, long-term uniaxial strain deterred collagen type III gene expression, whereas long-term circumferential strain upregulated both collagen type III and elastin gene expression. Finally, long-term uniaxial strain downregulated extracellular matrix (ECM) expression in more mature vSMC derivatives while upregulating elastin in less mature vSMC derivatives. Overall, our findings suggest that in vitro application of both cyclic uniaxial and circumferential tensile strain on hPSC-vSMC derivatives induces cell alignment and affects ECM gene expression. Therefore, mechanical stimulation of hPSC-vSMC derivatives using tensile strain may be important in modulating the phenotype and thus the function of vSMCs in tissue-engineered vessels.
Deficient acid handling with distal RTA in the NBCe2 knockout mouse
Authors: Wen Donghai , Yuan Yang , Cornelius Ryan J. , Li Huaqing , Warner Paige C. , Wang Bangchen , Wang-France Jun , Boettger Thomas , Sansom Steven C.
Published: June 2015

In many circumstances, the pathogenesis of distal renal tubular acidosis (dRTA) is not understood. In the present study, we report that a mouse model lacking the electrogenic Na+-HCO3−cotransporter [NBCe2/Slc4a5; NBCe2 knockout (KO) mice] developed dRTA after an oral acid challenge. NBCe2 expression was identified in the connecting tubule (CNT) of wild-type mice, and its expression was significantly increased after acid loading. NBCe2 KO mice did not have dRTA when on a standard mouse diet. However, after acid loading, NBCe2 KO mice exhibited complete features of dRTA, characterized by insufficient urinary acidification, hyperchloremic hypokalemic metabolic acidosis, and hypercalciuria. Additional experiments showed that NBCe2 KO mice had decreased luminal transepithelial potential in the CNT, as revealed by micropuncture. Further immunofluorescence and Western blot experiments found that NBCe2 KO mice had increased expression of H+-ATPase B1 in the plasma membrane. These results showed that NBCe2 KO mice with acid loading developed increased urinary K+and Ca2+wasting due to decreased luminal transepithelial potential in the CNT. NBCe2 KO mice compensated to maintain systemic pH by increasing H+-ATPase in the plasma membrane. Therefore, defects in NBCe2 can cause dRTA, and NBCe2 has an important role to regulate urinary acidification and the transport of K+and Ca2+in the distal nephron.
Glomerulosclerosis in the diet-induced obesity model correlates with sensitivity to nitric oxide inhibition but not glomerular hyperfiltration or hypertrophy
Authors: Polichnowski Aaron J. , Licea-Vargas Hector , Picken Maria , Long Jianrui , Bisla Rashmi , Williamson Geoffrey A. , Bidani Anil K. , Griffin Karen A.
Published: June 2015

The diet-induced obesity (DIO) model is frequently used to examine the pathogenesis of obesity-related pathologies; however, only minimal glomerulosclerosis (GS) has been reported after 3 mo. We investigated if GS develops over longer periods of DIO and examined the potential role of hemodynamic mechanisms in its pathogenesis. Eight-week-old male obesity-prone (OP) and obesity-resistant (OR) rats (Charles River) were administered a moderately high-fat diet for 5 mo. Radiotelemetrically measured blood pressure, proteinuria, and GS were assessed. OP ( n = 10) rats developed modest hypertension (142 ± 3 vs. 128 ± 2 mmHg, P < 0.05) and substantial levels of proteinuria (63 ± 12 vs. 12 ± 1 mg/day, P < 0.05) and GS (7.7 ± 1.4% vs. 0.4 ± 0.2%) compared with OR rats ( n = 8). Potential hemodynamic mechanisms of renal injury were assessed in additional groups of OP and OR rats fed a moderately high-fat diet for 3 mo. Kidney weight (4.3 ± 0.2 vs. 4.3 ± 0.1 g), glomerular filtration rate (3.3 ± 0.3 vs. 3.1 ± 0.1 ml/min), and glomerular volume (1.9 ± 0.1 vs. 2.0 ± 0.1 μm3× 10−6) were similar between OP ( n = 6) and OR ( n = 9) rats. Renal blood flow autoregulation was preserved in both OP ( n = 7) and OR ( n = 7) rats. In contrast, Nω-nitro-l-arginine methyl ester (l-NAME) administration in conscious, chronically instrumented OP ( n = 11) rats resulted in 15% and 39% increases in blood pressure and renal vascular resistance, respectively, and a 16% decrease in renal blood flow. Minimal effects of l-NAME were seen in OR ( n = 9) rats. In summary, DIO-associated GS is preceded by an increased hemodynamic sensitivity to l-NAME but not renal hypertrophy or hyperfiltration.
Parameter estimation for mathematical models of a nongastric H+(Na+)-K+(NH4+)-ATPase
Authors: Nadal-Quirós Mónica , Moore Leon C. , Marcano Mariano
Published: June 2015

The role of nongastric H+-K+-ATPase (HKA) in ion homeostasis of macula densa (MD) cells is an open question. To begin to explore this issue, we developed two mathematical models that describe ion fluxes through a nongastric HKA. One model assumes a 1H+:1K+-per-ATP stoichiometry; the other assumes a 2H+:2K+-per-ATP stoichiometry. Both models include Na+and NH4+competitive binding with H+and K+, respectively, a characteristic observed in vitro and in situ. Model rate constants were obtained by minimizing the distance between model and experimental outcomes. Both 1H+(1Na+):1K+(1NH4+)-per-ATP and 2H+(2Na+):2K+(2NH4+)-per-ATP models fit the experimental data well. Using both models, we simulated ion net fluxes as a function of cytosolic or luminal ion concentrations typical for the cortical thick ascending limb and MD region. We observed that 1) K+and NH4+flowed in the lumen-to-cytosol direction, 2) there was competitive behavior between luminal K+and NH4+and between cytosolic Na+and H+, 3) ion fluxes were highly sensitive to changes in cytosolic Na+or H+concentrations, and 4) the transporter does mostly Na+/K+exchange under physiological conditions. These results support the concept that nongastric HKA may contribute to Na+and pH homeostasis in MD cells. Furthermore, in both models, H+flux reversed at a luminal pH that was <5.6. Such reversal led to Na+/H+exchange for a luminal pH of <2 and 4 in the 1:1-per-ATP and 2:2-per-ATP models, respectively. This suggests a novel role of nongastric HKA in cell Na+homeostasis in the more acidic regions of the renal tubules.
Mapping of spatial and temporal heterogeneity of plantar flexor muscle activity during isometric contraction: correlation of velocity-encoded MRI with EMG
Authors: Csapo Robert , Malis Vadim , Sinha Usha , Sinha Shantanu
Published: June 2015

The aim of this study was to assess the correlation between contraction-associated muscle kinematics as measured by velocity-encoded phase-contrast (VE-PC) magnetic resonance imaging (MRI) and activity recorded via electromyography (EMG), and to construct a detailed three-dimensional (3-D) map of the contractile behavior of the triceps surae complex from the MRI data. Ten axial-plane VE-PC MRI slices of the triceps surae and EMG data were acquired during submaximal isometric contractions in 10 subjects. MRI images were analyzed to yield the degree of contraction-associated muscle displacement on a voxel-by-voxel basis and determine the heterogeneity of muscle movement within and between slices. Correlational analyses were performed to determine the agreement between EMG data and displacements. Pearson's coefficients demonstrated good agreement (0.84 < r < 0.88) between EMG data and displacements. Comparison between different slices in the gastrocnemius muscle revealed significant heterogeneity in displacement values both in-plane and along the cranio-caudal axis, with highest values in the mid-muscle regions. By contrast, no significant differences between muscle regions were found in the soleus muscle. Substantial differences among displacements were also observed within slices, with those in static areas being only 17–39% (maximum) of those in the most mobile muscle regions. The good agreement between EMG data and displacements suggests that VE-PC MRI may be used as a noninvasive, high-resolution technique for quantifying and modeling muscle activity over the entire 3-D volume of muscle groups. Application to the triceps surae complex revealed substantial heterogeneity of contraction-associated muscle motion both within slices and between different cranio-caudal positions.
High-intensity interval training without weight loss improves exercise but not basal or insulin-induced metabolism in overweight/obese African American women
Authors: Arad Avigdor D. , DiMenna Fred J. , Thomas Naketa , Tamis-Holland Jacqueline , Weil Richard , Geliebter Allan , Albu Jeanine B.
Published: June 2015

The purpose of this randomized controlled clinical trial was to determine the effect of a 14-week high-intensity interval training (HIIT) intervention with weight stability on metabolic flexibility, insulin sensitivity, and cardiorespiratory fitness in sedentary, premenopausal, nondiabetic, overweight/obese African American women. Twenty-eight subjects were allocated to one of two groups: HIIT, which performed three sessions per week of four high-intensity cycling intervals, or a control group (CON), which maintained their normal level of physical activity. Diet was controlled for all subjects to ensure weight stability. Pre- and postintervention (pre/post), subjects completed an incremental cycling test to limit of tolerance and, following a 10-day high-fat controlled feeding period, a euglycemic-hyperinsulinemic clamp to determine insulin sensitivity and substrate oxidation. Nine members of HIIT (age, 29 ± 4 yr; body mass, 90.1 ± 13.8 kg) and eleven members of CON (age, 30 ± 7 yr; body mass, 85.5 ± 10.7 kg) completed the study. HIIT experienced an increased limit of tolerance (post, 1,124 ± 202 s; pre, 987 ± 146 s; P < 0.05), gas exchange threshold (post, 1.29 ± 0.34 liters/min; pre, 0.97 ± 0.23 liters/min; P < 0.05), and fat oxidation at the same absolute submaximal work rate compared with CON ( P < 0.05 for group-by-time interaction in all cases). However, changes in peak oxygen consumption (V̇o2peak), insulin sensitivity, free fatty acid suppression during insulin stimulation, and metabolic flexibility were not different in HIIT compared with CON. High-intensity interval training with weight stability increased exercise fat oxidation and tolerance in subjects at risk for diabetic progression, but did not improve insulin sensitivity or fat oxidation in the postabsorptive or insulin-stimulated state.
Trichostatin A, a histone deacetylase inhibitor, modulates unloaded-induced skeletal muscle atrophy
Authors: Dupré-Aucouturier Sylvie , Castells Josiane , Freyssenet Damien , Desplanches Dominique
Published: June 2015

Skeletal muscle atrophy is commonly associated with immobilization, ageing, and catabolic diseases such as diabetes and cancer cachexia. Epigenetic regulation of gene expression resulting from chromatin remodeling through histone acetylation has been implicated in muscle disuse. The present work was designed to test the hypothesis that treatment with trichostatin A (TSA), a histone deacetylase inhibitor, would partly counteract unloading-induced muscle atrophy. Soleus muscle atrophy (−38%) induced by 14 days of rat hindlimb suspension was reduced to only 25% under TSA treatment. TSA partly prevented the loss of type I and IIa fiber size and reversed the transitions of slow-twitch to fast-twitch fibers in soleus muscle. Unloading or TSA treatment did not affect myostatin gene expression and follistatin protein. Soleus protein carbonyl content remained unchanged, whereas the decrease in glutathione vs. glutathione disulfide ratio and the increase in catalase activity (biomarkers of oxidative stress) observed after unloading were abolished by TSA treatment. The autophagy-lysosome pathway (Bnip3 and microtubule-associated protein 1 light chain 3 proteins, Atg5, Gabarapl1, Ulk1, and cathepsin B and L mRNA) was not activated by unloading or TSA treatment. However, TSA suppressed the rise in muscle-specific RING finger protein 1 (MuRF1) caused by unloading without affecting the forkhead box (Foxo3) transcription factor. Prevention of muscle atrophy by TSA might be due to the regulation of the skeletal muscle atrophy-related MuRF1 gene. Our findings suggest that TSA may provide a novel avenue to treat unloaded-induced muscle atrophy.
Hour-long adaptation in the awake early visual system
Authors: Stoelzel Carl R. , Huff Joseph M. , Bereshpolova Yulia , Zhuang (庄骏) Jun , Hei (黑晓娟) Xiaojuan , Alonso Jose-Manuel , Swadlow Harvey A.
Published: June 2015

Sensory adaptation serves to adjust awake brains to changing environments on different time scales. However, adaptation has been studied traditionally under anesthesia and for short time periods. Here, we demonstrate in awake rabbits a novel type of sensory adaptation that persists for >1 h and acts on visual thalamocortical neurons and their synapses in the input layers of the visual cortex. Following prolonged visual stimulation (10–30 min), cells in the dorsal lateral geniculate nucleus (LGN) show a severe and prolonged reduction in spontaneous firing rate. This effect is bidirectional, and prolonged visually induced response suppression is followed by a prolonged increase in spontaneous activity. The reduction in thalamic spontaneous activity following prolonged visual activation is accompanied by increases in 1) response reliability, 2) signal detectability, and 3) the ratio of visual signal/spontaneous activity. In addition, following such prolonged activation of an LGN neuron, the monosynaptic currents generated by thalamic impulses in layer 4 of the primary visual cortex are enhanced. These results demonstrate that in awake brains, prolonged sensory stimulation can have a profound, long-lasting effect on the information conveyed by thalamocortical inputs to the visual cortex.
Stimulus-dependent spiking relationships with the EEG
Authors: Snyder Adam C. , Smith Matthew A.
Published: June 2015

The development and refinement of noninvasive techniques for imaging neural activity is of paramount importance for human neuroscience. Currently, the most accessible and popular technique is electroencephalography (EEG). However, nearly all of what we know about the neural events that underlie EEG signals is based on inference, because of the dearth of studies that have simultaneously paired EEG recordings with direct recordings of single neurons. From the perspective of electrophysiologists there is growing interest in understanding how spiking activity coordinates with large-scale cortical networks. Evidence from recordings at both scales highlights that sensory neurons operate in very distinct states during spontaneous and visually evoked activity, which appear to form extremes in a continuum of coordination in neural networks. We hypothesized that individual neurons have idiosyncratic relationships to large-scale network activity indexed by EEG signals, owing to the neurons' distinct computational roles within the local circuitry. We tested this by recording neuronal populations in visual area V4 of rhesus macaques while we simultaneously recorded EEG. We found substantial heterogeneity in the timing and strength of spike-EEG relationships and that these relationships became more diverse during visual stimulation compared with the spontaneous state. The visual stimulus apparently shifts V4 neurons from a state in which they are relatively uniformly embedded in large-scale network activity to a state in which their distinct roles within the local population are more prominent, suggesting that the specific way in which individual neurons relate to EEG signals may hold clues regarding their computational roles.
Transspinal constant-current long-lasting stimulation: a new method to induce cortical and corticospinal plasticity
Authors: Knikou Maria , Dixon Luke , Santora Danielle , Ibrahim Mohamed M.
Published: June 2015

Functional neuroplasticity in response to stimulation and motor training is a well-established phenomenon. Transcutaneous stimulation of the spine is used mostly to alleviate pain, but it may also induce functional neuroplasticity, because the spinal cord serves as an integration center for descending and ascending neuronal signals. In this work, we examined whether long-lasting noninvasive cathodal (c-tsCCS) and anodal (a-tsCCS) transspinal constant-current stimulation over the thoracolumbar enlargement can induce cortical, corticospinal, and spinal neuroplasticity. Twelve healthy human subjects, blind to the stimulation protocol, were randomly assigned to 40 min of c-tsCCS or a-tsCCS. Before and after transspinal stimulation, we established the afferent-mediated motor evoked potential (MEP) facilitation and the subthreshold transcranial magnetic stimulation (TMS)-mediated flexor reflex facilitation. Recruitment input-output curves of MEPs and transspinal evoked potentials (TEPs) and postactivation depression of the soleus H reflex and TEPs was also established. We demonstrate that both c-tsCCS and a-tsCCS decrease the afferent-mediated MEP facilitation and alter the subthreshold TMS-mediated flexor reflex facilitation in a polarity-dependent manner. Both c-tsCCS and a-tsCCS increased the tibialis anterior MEPs recorded at 1.2 MEP resting threshold, intermediate, and maximal intensities and altered the recruitment input-output curve of TEPs in a muscle- and polarity-dependent manner. Soleus H-reflex postactivation depression was reduced after a-tsCCS and remained unaltered after c-tsCCS. No changes were found in the postactivation depression of TEPs after c-tsCCS or a-tsCCS. Our findings reveal that c-tsCCS and a-tsCCS have distinct effects on cortical and corticospinal excitability. This method can be utilized to induce targeted neuroplasticity in humans.
A model for attentional information routing through coherence predicts biased competition and multistable perception
Authors: Harnack Daniel , Ernst Udo Alexander , Pawelzik Klaus Richard
Published: June 2015

Selective attention allows to focus on relevant information and to ignore distracting features of a visual scene. These principles of information processing are reflected in response properties of neurons in visual area V4: if a neuron is presented with two stimuli in its receptive field, and one is attended, it responds as if the nonattended stimulus was absent (biased competition). In addition, when the luminance of the two stimuli is temporally and independently varied, local field potentials are correlated with the modulation of the attended stimulus and not, or much less, correlated with the nonattended stimulus (information routing). To explain these results in one coherent framework, we present a two-layer spiking cortical network model with distance-dependent lateral connectivity and converging feed-forward connections. With oscillations arising inherently from the network structure, our model reproduces both experimental observations. Hereby, lateral interactions and shifts of relative phases between sending and receiving layers (communication through coherence) are identified as the main mechanisms underlying both biased competition as well as selective routing. Exploring the parameter space, we show that the effects are robust and prevalent over a broad range of parameters. In addition, we identify the strength of lateral inhibition in the first model layer as crucial for determining the working regime of the system: increasing lateral inhibition allows a transition from a network configuration with mixed representations to one with bistable representations of the competing stimuli. The latter is discussed as a possible neural correlate of multistable perception phenomena such as binocular rivalry.
Compensatory stepping in Parkinson's disease is still a problem after deep brain stimulation randomized to STN or GPi
Authors: St George R. J. , Carlson-Kuhta P. , King L. A. , Burchiel K. J. , Horak F. B.
Published: June 2015

The effects of deep brain stimulation (DBS) on balance in people with Parkinson's disease (PD) are not well established. This study examined whether DBS randomized to the subthalamic nucleus (STN; n = 11) or globus pallidus interna (GPi; n = 10) improved compensatory stepping to recover balance after a perturbation. The standing surface translated backward, forcing subjects to take compensatory steps forward. Kinematic and kinetic responses were recorded. PD-DBS subjects were tested off and on their levodopa medication before bilateral DBS surgery and retested 6 mo later off and on DBS, combined with off and on levodopa medication. Responses were compared with PD-control subjects ( n = 8) tested over the same timescale and 17 healthy control subjects. Neither DBS nor levodopa improved the stepping response. Compensatory stepping in the best-treated state after surgery (DBS+DOPA) was similar to the best-treated state before surgery (DOPA) for the PD-GPi group and the PD-control group. For the PD-STN group, there were more lateral weight shifts, a delayed foot-off, and a greater number of steps required to recover balance in DBS+DOPA after surgery compared with DOPA before surgery. Within the STN group five subjects who did not fall during the experiment before surgery fell at least once after surgery, whereas the number of falls in the GPi and PD-control groups were unchanged. DBS did not improve the compensatory step response needed to recover from balance perturbations in the GPi group and caused delays in the preparation phase of the step in the STN group.
Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting
Authors: Tintignac Lionel A. , Brenner Hans-Rudolf , Rüegg Markus A.
Published: June 2015

The neuromuscular junction is the chemical synapse between motor neurons and skeletal muscle fibers. It is designed to reliably convert the action potential from the presynaptic motor neuron into the contraction of the postsynaptic muscle fiber. Diseases that affect the neuromuscular junction may cause failure of this conversion and result in loss of ambulation and respiration. The loss of motor input also causes muscle wasting as muscle mass is constantly adapted to contractile needs by the balancing of protein synthesis and protein degradation. Finally, neuromuscular activity and muscle mass have a major impact on metabolic properties of the organisms. This review discusses the mechanisms involved in the development and maintenance of the neuromuscular junction, the consequences of and the mechanisms involved in its dysfunction, and its role in maintaining muscle mass during aging. As life expectancy is increasing, loss of muscle mass during aging, called sarcopenia, has emerged as a field of high medical need. Interestingly, aging is also accompanied by structural changes at the neuromuscular junction, suggesting that the mechanisms involved in neuromuscular junction maintenance might be disturbed during aging. In addition, there is now evidence that behavioral paradigms and signaling pathways that are involved in longevity also affect neuromuscular junction stability and sarcopenia.
Synthesis, Characterization, and Anticancer Activity of New Metal Complexes Derived from 2-Hydroxy-3-(hydroxyimino)-4-oxopentan-2-ylidene)benzohydrazide
Authors: El-Tabl Abdou Saad , Mohamed Abd El-Waheed Moshira , Wahba Mohammed Ahmed , Abd El-Halim Abou El-Fadl Nahla
Published: June 2015

Novel metal(II) complexes derived from 2-hydroxy-N′-((Z)-3-(hydroxyimino)-4-oxopentan-2-ylidene)benzohydrazide ligand (H2L) were synthesized and characterized by elemental and thermal analyses (DTA and TGA), IR, UV-VIS,1H-NMR, ESR and mass spectroscopy, magnetic susceptibilities, and conductivities measurements. The complexes adopt distorted octahedral geometry. The ESR spectra of the solid copper(II) complexes are characteristic tod9configuration and have an axial symmetry type of ad(x2-y2)ground state. Thegvalues confirmed the tetragonal octahedral geometry with a considerably ionic or covalent environment. The cytotoxic activity of the ligand and its metal complexes showed potent cytotoxicity effect against growth of human liver cancer HepG2 cell lines compared to the clinically used Sorafenib (Nexavar).
Fuzzy Availability Assessment for a Repairable Multistate Series-Parallel System
Authors: Hu Linmin , Yue Dequan , Tian Ruiling
Published: June 2015

This paper considers a repairable multistate series-parallel system (RMSSPS) with fuzzy parameters. It is assumed that the system components are independent, and their state transition rates and performance rates are fuzzy values. The fuzzy universal generating function technique is adopted to determine fuzzy state probability and fuzzy performance rate of the system. On the basis ofα-cut approach and the extension principle, parametric programming technique is employed to obtain theα-cuts of some indices for the system. The system fuzzy availability is defined as the ability of the system to satisfy fuzzy consumer demand. A special assessment approach is developed for evaluating the fuzzy steady-state availability of the system with the fuzzy demand. A flow transmission system with three components is presented to demonstrate the validity of the proposed method.
Piezoelectric Nanowires in Energy Harvesting Applications
Authors: Wang Zhao , Pan Xumin , He Yahua , Hu Yongming , Gu Haoshuang , Wang Yu
Published: June 2015

Recently, the nanogenerators which can convert the mechanical energy into electricity by using piezoelectric one-dimensional nanomaterials have exhibited great potential in microscale power supply and sensor systems. In this paper, we provided a comprehensive review of the research progress in the last eight years concerning the piezoelectric nanogenerators with different structures. The fundamental piezoelectric theory and typical piezoelectric materials are firstly reviewed. After that, the working mechanism, modeling, and structure design of piezoelectric nanogenerators were discussed. Then the recent progress of nanogenerators was reviewed in the structure point of views. Finally, we also discussed the potential application and future development of the piezoelectric nanogenerators.
Performance Analysis of CFRP Composite Strips Confined RC Columns under Axial Compression
Authors: Murugadoss J. Raja , Lee Byung Jae , Bang Jin Wook , Ganesh Prabhu G. , Kim Yun Yong
Published: June 2015

In an attempt to mitigate the high cost of FRP composite strengthening, an experimental investigation was carried out that sought to achieve efficient and most favorable FRP strengthening using CFRP composite strips. 50 mm wide CFRP composite strips were used in two different spacings (20 mm and 40 mm) to confine columns. The test results of the column confined with smaller spacing (20 mm) showed significant restraint of axial deformation of the column and enhanced the strength capacity to a maximum of 99.20% compared to that of reference column. In contrast, the column confined by strips with larger spacing (40 mm) failed by crushing of concrete alone, which occurred even before the CFRP strips reached their ultimate strain. In addition, the embodied energy that exists in the CFRP strips could not be utilized effectively. The stress and strength enhancement ratio of this present study was compared with the previous research that has been conducted on columns confined with full wrapping. From the obtained results, it is recommended that CFRP strips with a spacing of 20 mm be used to improve the strength capacity of the RC column; in addition, this wrapping technique provides economic benefits compared to a column confined with full wrapping.
Tensile Behavior of Polyetheretherketone over a Wide Range of Strain Rates
Authors: El-Qoubaa Zakaria , Othman Ramzi
Published: June 2015

Polyetheretherketone (PEEK) is used in several engineering applications where it has to bear impact loads. Nevertheless, the tensile behavior has only been studied in the quasi-static range of loading rates. To address the lack of data in the impact strain rate range, the tensile mechanical behavior of PEEK is investigated at room temperature over a large range of strain rates (from 0.001 to 1000/s). The macroscopic volume change is studied under uniaxial tension using digital image correlation (DIC) method, showing a significant dilatation that reaches 16% at a logarithmic axial strain of 40%. The true stress-strain behavior is therefore established based on the measured volume change. Elsewhere, the yield stress shows a significant sensitivity to strain rate. Besides, a new constitutive equation is proposed to take into account the increase in strain rate sensitivity at high strain rates. It assumes an apparent activation volume which decreases as the strain rate increases. The new constitutive equation gives similar results when compared to the Ree-Eyring equation. However, only three material constants are to be identified and are physically interpreted.
A Performance Study of a Dual Xeon-Phi Cluster for the Forward Modelling of Gravitational Fields
Authors: Arroyo Maricela , Couder-Castañeda Carlos , Trujillo-Alcantara Alfredo , Herrera-Diaz Israel-Enrique , Vera-Chavez Nain
Published: June 2015

With at least 60 processing cores, the Xeon-Phi coprocessor is a truly multicore architecture, which consists of an interconnection speed among cores of 240 GB/s, two levels of cache memory, a theoretical performance of 1.01 Tflops, and programming flexibility, all making the Xeon-Phi an excellent coprocessor for parallelizing applications that seek to reduce computational times. The objective of this work is to migrate a geophysical application designed to directly calculate the gravimetric tensor components and their derivatives and in this way research the performance of one and two Xeon-Phi coprocessors integrated on the same node and distributed in various nodes. This application allows the analysis of the design factors that drive good performance and compare the results against a conventional multicore CPU. This research shows an efficient strategy based on nested parallelism using OpenMP, a design that in its outer structure acts as a controller of interconnected Xeon-Phi coprocessors while its interior is used for parallelyzing the loops. MPI is subsequently used to reduce the information among the nodes of the cluster.
Novel Antioxidant Tripeptide “ACQ” Can Prevent UV-Induced Cell Death and Preserve the Number of Epidermal Stem Cells
Authors: Choi Hye-Ryung , Shin Jung-Won , Na Jung-Im , Nam Kyung-Mi , Lee Hyun-Sun , Park Kyoung-Chan
Published: June 2015

We found that tripeptide “ACQ: alanine-cysteine-glutamine” has significant DPPH scavenging activity compared to that of glutathione. Antioxidant effects of ACQ were tested inin vitroandin vivomodels. When treated with H2O2, mock treated fibroblasts and keratinocytes showed strong staining by H2DCFA. But, ACQ showed good protective effects against hydrogen peroxide treatment. When mice were fed for 2 or 4 weeks, similar protective effects were observed. In the control group, epidermis was severely damaged by UV irradiation and apoptotic keratinocytes were observed. There were also numerous TUNEL positive cells. But in the ACQ group, epidermis became thicker and there was no sign of severe damage. Interestingly, the number of p63 cells was also higher in ACQ fed mice. To confirm the stem cell rescuing effects of ACQ, three-dimensional skin samples were constructed. Results showed that ACQ increased the expression of integrinα6 and the number of p63 positive cells. These findings showed that ACQ has good antioxidant activity and may increase stem cell activities by the regulation of integrinα6.