bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of nitrate supplementation on hepatic blood flow and glucose homeostasis: a double-blind, placebo-controlled, randomized control trial
Authors: Shepherd Anthony I. , Wilkerson Daryl P. , Fulford Jon , Winyard Paul G. , Benjamin Nigel , Shore Angela C. , Gilchrist Mark
Published: July 2016

Nitric oxide alters gastric blood flow, improves vascular function, and mediates glucose uptake within the intestines and skeletal muscle. Dietary nitrate, acting as a source of nitric oxide, appears to be a potential low-cost therapy that may help maintain glucose homeostasis. In a randomized, double-blind, placebo-controlled crossover study, 31 young and older adult participants had a standardized breakfast, supplemented with either nitrate-rich beetroot juice (11.91 mmol nitrate) or nitrate-depleted beetroot juice as placebo (0.01 mmol nitrate). MRI was used to assess apparent diffusion coefficient (ADC), portal vein flux, and velocity. Plasma glucose, incretin, and C-peptide concentrations and blood pressure were assessed. Outcome variables were measured at baseline and hourly for 3 h. Compared with a placebo, beetroot juice resulted in a significant elevation in plasma nitrate and plasma nitrite concentration. No differences were seen for the young or older adult cohorts between placebo and beetroot juice for ADC, or portal vein flux. There was an interaction effect in the young adults between visits for portal vein velocity. Nitrate supplementation did not reduce plasma glucose, active GLP-1, total GLP-1, or plasma C-peptide concentrations for the young or older adult cohorts. Despite a significant elevation in plasma nitrite concentration following an acute dose of (11.91 mmol) nitrate, there was no effect on hepatic blood flow, plasma glucose, C-peptide, or incretin concentration in healthy adults.
The role of cGMP and its signaling pathways in kidney disease
Authors: Shen Kunyu , Johnson David W. , Gobe Glenda C.
Published: July 2016

Cyclic nucleotide signal transduction pathways are an emerging research field in kidney disease. Activated cell surface receptors transduce their signals via intracellular second messengers such as cAMP and cGMP. There is increasing evidence that regulation of the cGMP-cGMP-dependent protein kinase 1-phosphodiesterase (cGMP-cGK1-PDE) signaling pathway may be renoprotective. Selective PDE5 inhibitors have shown potential in treating kidney fibrosis in patients with chronic kidney disease (CKD), via their downstream signaling, and these inhibitors also have known activity as antithrombotic and anticancer agents. This review gives an outline of the cGMP-cGK1-PDE signaling pathways and details the downstream signaling and regulatory functions that are modulated by cGK1 and PDE inhibitors with regard to antifibrotic, antithrombotic, and antitumor activity. Current evidence that supports the renoprotective effects of regulating cGMP-cGK1-PDE signaling is also summarized. Finally, the effects of icariin, a natural plant extract with PDE5 inhibitory function, are discussed. We conclude that regulation of cGMP-cGK1-PDE signaling might provide novel, therapeutic strategies for the worsening global public health problem of CKD.
Mechanisms of connecting tubule glomerular feedback enhancement by aldosterone
Authors: Ren YiLin , Janic Branislava , Kutskill Kristopher , Peterson Edward L. , Carretero Oscar A.
Published: July 2016

Connecting tubule glomerular feedback (CTGF) is a mechanism where an increase in sodium (Na) concentration in the connecting tubule (CNT) causes the afferent arteriole (Af-Art) to dilate. We recently reported that aldosterone within the CNT lumen enhances CTGF via a nongenomic effect involving GPR30 receptors and sodium/hydrogen exchanger (NHE), but the signaling pathways of this mechanism are unknown. We hypothesize that aldosterone enhances CTGF via cAMP/protein kinase A (PKA) pathway that activates protein kinase C (PKC) and stimulates superoxide (O2−) production. Rabbit Af-Arts and their adherent CNTs were microdissected and simultaneously perfused. Two consecutive CTGF curves were elicited by increasing the CNT luminal NaCl. We found that the main effect of aldosterone was to sensitize CTGF and we analyzed data by comparing NaCl concentration in the CNT perfusate needed to achieve half of the maximal response (EC50). During the control period, the NaCl concentration that elicited a half-maximal response (EC50) was 37.0 ± 2.0 mmol/l; addition of aldosterone (10−8 mol/l) to the CNT lumen decreased EC50 to 19.3 ± 1.3 mmol/l ( P ≤ 0.001 vs. Control). The specific adenylyl cyclase inhibitor 2′,3′-dideoxyadenosine (ddA; 2 × 10−4 mol/l) and the PKA inhibitor H-89 dihydrochloride hydrate (H-89; 2 × 10−6 mol/l) prevented the aldosterone effect. The selective PKC inhibitor GF109203X (10−8 mol/l) also prevented EC50 reduction caused by aldosterone. CNT intraluminal addition of O2− scavenger tempol (10−4 mol/l) blocked the aldosterone effect. We conclude that aldosterone inside the CNT lumen enhances CTGF via a cAMP/PKA/PKC pathway and stimulates O2− generation and this process may contribute to renal damage by increasing glomerular capillary pressure.
Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development
Authors: Tinning Anne R. , Jensen Boye L. , Johnsen Iben , Chen Daian , Coffman Thomas M. , Madsen Kirsten
Published: July 2016

Postnatal inhibition or deletion of angiotensin II (ANG II) AT1receptors impairs renal medullary mircrovascular development through a mechanism that may include vascular endothelial growth factor (VEGF). The present study was designed to test if VEGF/VEGF receptor signaling is necessary for the development of the renal medullary microcirculation. Endothelial cell-specific immunolabeling of kidney sections from rats showed immature vascular bundles at postnatal day (P) 10 with subsequent expansion of bundles until P21. Medullary VEGF protein abundance coincided with vasa recta bundle formation. In human fetal kidney tissue, immature vascular bundles appeared early in the third trimester (GA27-28) and expanded in size until term. Rat pups treated with the VEGF receptor-2 (VEGFR2) inhibitor vandetanib (100 mg·kg−1·day−1) from P7 to P12 or P10 to P16 displayed growth retardation and proteinuria. Stereological quantification showed a significant reduction in total length (386 ± 13 vs. 219 ± 16 m), surface area, and volume of medullary microvessels. Vascular bundle architecture was unaffected. ANG II-AT1A/1B−/−mice kidneys displayed poorly defined vasa recta bundles whereas mice with collecting duct principal cell-specific AT1Adeletion displayed no medullary microvascular phenotype. In conclusion, VEGFR2 signaling during postnatal development is necessary for expansion of the renal medullary microcirculation but not structural patterning of the vasa recta bundles, which occurs through an AT1-mediated mechanism.
SGK1-dependent ENaC processing and trafficking in mice with high dietary K intake and elevated aldosterone
Authors: Yang Lei , Frindt Gustavo , Lang Florian , Kuhl Dietmar , Vallon Volker , Palmer Lawrence G.
Published: July 2016

We examined renal Na and K transporters in mice with deletions in the gene encoding the aldosterone-induced protein SGK1. The knockout mice were hyperkalemic, and had altered expression of the subunits of the epithelial Na channel (ENaC). The kidneys showed decreased expression of the cleaved forms of the γENaC subunit, and the fully glycosylated form of the βENaC subunits when animals were fed a high-K diet. Knockout animals treated with exogenous aldosterone also had reduced subunit processing and diminished surface expression of βENaC and γENaC. Expression of the three upstream Na transporters NHE3, NKCC2, and NCC was reduced in both wild-type and knockout mice in response to K loading. The activity of ENaC measured as whole cell amiloride-sensitive current ( INa) in principal cells of the cortical collecting duct (CCD) was minimal under control conditions but was increased by a high-K diet to a similar extent in knockout and wild-type animals. INa in the connecting tubule also increased similarly in the two genotypes in response to exogenous aldosterone administration. The activities of both ROMK channels in principal cells and BK channels in intercalated cells of the CCD were unaffected by the deletion of SGK1. Acute treatment of animals with amiloride produced similar increases in Na excretion and decreases in K excretion in the two genotypes. The absence of changes in ENaC activity suggests compensation for decreased surface expression. Altered K balance in animals lacking SGK1 may reflect defects in ENaC-independent K excretion.
Velocity dependence of vestibular information for postural control on tilting surfaces
Authors: Horak Fay B. , Kluzik JoAnn , Hlavacka Frantisek
Published: July 2016

Vestibular information is known to be important for postural stability on tilting surfaces, but the relative importance of vestibular information across a wide range of surface tilt velocities is less clear. We compared how tilt velocity influences postural orientation and stability in nine subjects with bilateral vestibular loss and nine age-matched, control subjects. Subjects stood on a force platform that tilted 6 deg, toes-up at eight velocities (0.25 to 32 deg/s), with and without vision. Results showed that visual information effectively compensated for lack of vestibular information at all tilt velocities. However, with eyes closed, subjects with vestibular loss were most unstable within a critical tilt velocity range of 2 to 8 deg/s. Subjects with vestibular deficiency lost their balance in more than 90% of trials during the 4 deg/s condition, but never fell during slower tilts (0.25–1 deg/s) and fell only very rarely during faster tilts (16–32 deg/s). At the critical velocity range in which falls occurred, the body center of mass stayed aligned with respect to the surface, onset of ankle dorsiflexion was delayed, and there was delayed or absent gastrocnemius inhibition, suggesting that subjects were attempting to actively align their upper bodies with respect to the moving surface instead of to gravity. Vestibular information may be critical for stability at velocities of 2 to 8 deg/s because postural sway above 2 deg/s may be too fast to elicit stabilizing responses through the graviceptive somatosensory system, and postural sway below 8 deg/s may be too slow for somatosensory-triggered responses or passive stabilization from trunk inertia.
Air-Track: a real-world floating environment for active sensing in head-fixed mice
Authors: Nashaat Mostafa A. , Oraby Hatem , Sachdev Robert N. S. , Winter York , Larkum Matthew E.
Published: July 2016

Natural behavior occurs in multiple sensory and motor modalities and in particular is dependent on sensory feedback that constantly adjusts behavior. To investigate the underlying neuronal correlates of natural behavior, it is useful to have access to state-of-the-art recording equipment (e.g., 2-photon imaging, patch recordings, etc.) that frequently requires head fixation. This limitation has been addressed with various approaches such as virtual reality/air ball or treadmill systems. However, achieving multimodal realistic behavior in these systems can be challenging. These systems are often also complex and expensive to implement. Here we present “Air-Track,” an easy-to-build head-fixed behavioral environment that requires only minimal computational processing. The Air-Track is a lightweight physical maze floating on an air table that has all the properties of the “real” world, including multiple sensory modalities tightly coupled to motor actions. To test this system, we trained mice in Go/No-Go and two-alternative forced choice tasks in a plus maze. Mice chose lanes and discriminated apertures or textures by moving the Air-Track back and forth and rotating it around themselves. Mice rapidly adapted to moving the track and used visual, auditory, and tactile cues to guide them in performing the tasks. A custom-controlled camera system monitored animal location and generated data that could be used to calculate reaction times in the visual and somatosensory discrimination tasks. We conclude that the Air-Track system is ideal for eliciting natural behavior in concert with virtually any system for monitoring or manipulating brain activity.
Perimovement decrease of alpha/beta oscillations in the human nucleus accumbens
Authors: Stenner Max-Philipp , Dürschmid Stefan , Rutledge Robb B. , Zaehle Tino , Schmitt Friedhelm C. , Kaufmann Jörn , Voges Jürgen , Heinze Hans-Jochen , Dolan Raymond J. , Schoenfeld Mircea Ariel
Published: July 2016

The human nucleus accumbens is thought to play an important role in guiding future action selection via an evaluation of current action outcomes. Here we provide electrophysiological evidence for a more direct, i.e., online, role during action preparation. We recorded local field potentials from the nucleus accumbens in patients with epilepsy undergoing surgery for deep brain stimulation. We found a consistent decrease in the power of alpha/beta oscillations (10–30 Hz) before and around the time of movements. This perimovement alpha/beta desynchronization was observed in seven of eight patients and was present both before instructed movements in a serial reaction time task as well as before self-paced, deliberate choices in a decision making task. A similar beta decrease over sensorimotor cortex and in the subthalamic nucleus has been directly related to movement preparation and execution. Our results support the idea of a direct role of the human nucleus accumbens in action preparation and execution.
Initial information prior to movement onset influences kinematics of upward arm pointing movements
Authors: Rousseau Célia , Papaxanthis Charalambos , Gaveau Jérémie , Pozzo Thierry , White Olivier
Published: July 2016

To elaborate a motor plan and perform online control in the gravity field, the brain relies on priors and multisensory integration of information. In particular, afferent and efferent inputs related to the initial state are thought to convey sensorimotor information to plan the upcoming action. Yet it is still unclear to what extent these cues impact motor planning. Here we examined the role of initial information on the planning and execution of arm movements. Participants performed upward arm movements around the shoulder at three speeds and in two arm conditions. In the first condition, the arm was outstretched horizontally and required a significant muscular command to compensate for the gravitational shoulder torque before movement onset. In contrast, in the second condition the arm was passively maintained in the same position with a cushioned support and did not require any muscle contraction before movement execution. We quantified differences in motor performance by comparing shoulder velocity profiles. Previous studies showed that asymmetric velocity profiles reflect an optimal integration of the effects of gravity on upward movements. Consistent with this, we found decreased acceleration durations in both arm conditions. However, early differences in kinematic asymmetries and EMG patterns between the two conditions signaled a change of the motor plan. This different behavior carried on through trials when the arm was at rest before movement onset and may reveal a distinct motor strategy chosen in the context of uncertainty. Altogether, we suggest that the information available online must be complemented by accurate initial information.
The antiepileptic and ictogenic effects of optogenetic neurostimulation of PV-expressing interneurons
Authors: Assaf Fadi , Schiller Yitzhak
Published: July 2016

Parvalbumin (PV)-expressing interneurons exert powerful inhibitory effects on the normal cortical network; thus optogenetic activation of PV interneurons may also possess antiepileptic properties. To investigate this possibility we expressed channelrhodopsin 2 in PV interneurons by locally injecting the Cre-dependent viral vector AAV2/1-EF1a-DIO-ChETA-EYFP into the S1 barrel cortex of PV-Cre mice. Approximately 3–4 wk later recurrent electrographic seizures were evoked by local application of the chemoconvulsant 4-aminopyridine (4-AP); the ECoG and unit activity were monitored with extracellular silicone electrodes; and PV interneurons were activated optogenetically during the ictal and interictal phases. Five- to ten-second optogenetic activation of PV interneurons applied during electrographic seizures (ictal phase) terminated 33.7% of electrographic seizures compared with only 6% during sham stimulation, and the average electrographic seizure duration shortened by 38.7 ± 34.2% compared with sham stimulation. In contrast, interictal optogenetic activation of PV interneurons showed powerful and robust ictogenic effects. Approximately 60% of interictal optogenetic stimuli resulted in electrographic seizure initiation. Single-unit recordings revealed that presumptive PV-expressing interneurons markedly increased their firing during optogenetic stimulation, while many presumptive excitatory pyramidal neurons showed a biphasic response, with initial suppression of firing during the optogenetic pulse followed by a synchronized rebound increase in firing at the end of the laser pulse. Our findings indicated that ictal activation of PV-expressing interneurons possesses antiepileptic properties probably due to suppression of firing in pyramidal neurons during the laser pulse. However, in addition interictal activation of PV-expressing interneurons possesses powerful ictogenic properties, probably due to synchronized postinhibition rebound firing of pyramidal neurons.
Growth restriction induced by chronic prenatal hypoxia affects breathing rhythm and its pontine catecholaminergic modulation
Authors: Tree K. , Viemari J. C. , Cayetanot F. , Peyronnet J.
Published: July 2016

Impaired transplacental supply of oxygen leads to intrauterine growth restriction, one of the most important causes of perinatal mortality and respiratory morbidity. Breathing rhythm depends on the central respiratory network modulated by catecholamines. We investigated the impact of growth restriction, using prenatal hypoxia, on respiratory frequency, on central respiratory-like rhythm, and on its catecholaminergic modulation after birth. At birth, respiratory frequency was increased and confirmed in en bloc medullary preparations, where the frequency of the fourth cervical (C4) ventral root discharge was increased, and in slice preparations containing the pre-Bötzinger complex with an increased inspiratory rhythm. The inhibition of C4 burst discharge observed in pontomedullary preparations was stronger in the growth-restricted group. These results cannot be directly linked by the tyrosine hydroxylase activity increase of A1/C1and A2/C2cell groups in the medulla since blockade of α1- and α2-adrenergic receptors did not abolish the difference between both groups. However, in pontomedullary preparations, the stronger inhibition of C4 burst discharge is probably supported by an increased inhibition of A5, a respiratory rhythm inhibitor pontine group of neurons displaying increased tyrosine hydroxylase activity, because blockade of α2-adrenergic receptors abolished the difference between the two groups. Taken together, these results indicate that growth restriction leads to a perturbation of the breathing frequency, which finds, at least in part, its origin in the modification of catecholaminergic modulation of the central breathing network.
Savings for visuomotor adaptation require prior history of error, not prior repetition of successful actions
Authors: Leow Li-Ann , de Rugy Aymar , Marinovic Welber , Riek Stephan , Carroll Timothy J.
Published: July 2016

When we move, perturbations to our body or the environment can elicit discrepancies between predicted and actual outcomes. We readily adapt movements to compensate for such discrepancies, and the retention of this learning is evident as savings, or faster readaptation to a previously encountered perturbation. The mechanistic processes contributing to savings, or even the necessary conditions for savings, are not fully understood. One theory suggests that savings requires increased sensitivity to previously experienced errors: when perturbations evoke a sequence of correlated errors, we increase our sensitivity to the errors experienced, which subsequently improves error correction (Herzfeld et al. 2014). An alternative theory suggests that a memory of actions is necessary for savings: when an action becomes associated with successful target acquisition through repetition, that action is more rapidly retrieved at subsequent learning (Huang et al. 2011). In the present study, to better understand the necessary conditions for savings, we tested how savings is affected by prior experience of similar errors and prior repetition of the action required to eliminate errors using a factorial design. Prior experience of errors induced by a visuomotor rotation in the savings block was either prevented at initial learning by gradually removing an oppositely signed perturbation or enforced by abruptly removing the perturbation. Prior repetition of the action required to eliminate errors in the savings block was either deprived or enforced by manipulating target location in preceding trials. The data suggest that prior experience of errors is both necessary and sufficient for savings, whereas prior repetition of a successful action is neither necessary nor sufficient for savings.
Subretinal electrical stimulation reveals intact network activity in the blind mouse retina
Authors: Stutzki Henrike , Helmhold Florian , Eickenscheidt Max , Zeck Günther
Published: July 2016

Retinal degeneration ( rd) leads to progressive photoreceptor cell death, resulting in vision loss. Stimulation of the inner-retinal neurons by neuroprosthetic implants is one of the clinically approved vision-restoration strategies, providing basic visual percepts to blind patients. However, little is understood as to what degree the degenerating retinal circuitry and the resulting aberrant hyperactivity may prevent the stimulation of physiological electrical activity. Therefore, we electrically stimulated ex vivo retinas from wild-type ( wt; C57BL/6J) and blind ( rd10 and rd1) mice using an implantable subretinal microchip and simultaneously recorded and analyzed the retinal ganglion cell (RGC) output with a flexible microelectrode array. We found that subretinal anodal stimulation of the rd10 retina and wt retina evoked similar spatiotemporal RGC-spiking patterns. In both retinas, electrically stimulated ON and a small percentage of OFF RGC responses were detected. The spatial selectivity of the retinal network to electrical stimuli reveals an intact underlying network with a median receptive-field center of 350 μm in both retinas. An antagonistic surround is activated by stimulation with large electrode fields. However, in rd10 and to a higher percentage, in rd1 retinas, rhythmic and spatially unconfined RGC patterns were evoked by anodal or by cathodal electrical stimuli. Our findings demonstrate that the surviving retinal circuitry in photoreceptor-degenerated retinas is preserved in a way allowing for the stimulation of temporally diverse and spatially confined RGC activity. Future vision restoration strategies can build on these results but need to avoid evoking the easily inducible rhythmic activity in some retinal circuits.
Generation of Soluble Interleukin-11 and Interleukin-6 Receptors: A Crucial Function for Proteases during Inflammation
Authors: Lokau Juliane , Agthe Maria , Garbers Christoph
Published: July 2016

The cytokines interleukin-11 (IL-11) and IL-6 are important proteins with well-defined pro- and anti-inflammatory functions. They activate intracellular signaling cascades through a homodimer of the ubiquitously expressed signal-transducingβ-receptor glycoprotein 130 (gp130). Specificity is gained through the cell- and tissue-specific expression of the nonsignaling IL-11 and IL-6α-receptors (IL-11R and IL-6R), which determine the responsiveness of the cell to these two cytokines. IL-6 is a rare example, where its soluble receptor (sIL-6R) has agonistic properties, so that the IL-6/sIL-6R complex is able to activate cells that are usually not responsive to IL-6 alone (trans-signaling). Recent evidence suggests that IL-11 can signal via a similar trans-signaling mechanism. In this review, we highlight similarities and differences in the functions of IL-11 and IL-6. We summarize current knowledge about the generation of the sIL-6R and sIL-11R by different proteases and discuss possible roles during inflammatory processes. Finally, we focus on the selective and/or combined inhibition of IL-6 and IL-11 signaling and how this might translate into the clinics.
A Tobacco-Derived Thymosinβ4 Concatemer Promotes Cell Proliferation and Wound Healing in Mice
Authors: Janarthini Rylosona , Wang Xiaolei , Chen Lulu , Gao Lei , Zhao Lingxia
Published: July 2016

Thymosinβ4 (Tβ4) is a peptide that is known to play important roles in protection, regeneration, and remodeling of injured tissues in humans, and that shows great promise in a range of clinical applications. However, current strategies to Tβ4 are insufficient to meet growing demand and have a number of limitations. In this current study we investigated whether expression of recombinant Tβ4 in plants, specifically in tobacco (Nicotiana tabacum) leaves, represents an effective approach. To address this question, a 168 bpTβ4gene optimized for tobacco codon usage bias was constitutively expressed in tobacco as a 4-unit repeat concatemer, fused to a polyhistidine tag. Quantitative polymerase chain reaction and Western blot analyses were used to verify4×Tβ4expression in 14 transgenic tobacco lines and enzyme-linked immunosorbent assay analysis indicated 4×Tβ4 protein concentrations as high as 3 μg/g of fresh weight in the leaves. We observed that direct administration of tobacco-derived Tβ4 was more effective than Tβ4 either obtained commercially or derived from expression inEscherichia coliat promoting splenocyte proliferationin vitroand wound healing in mice through an endothelial migration assay. This study provides new insights into the development of plant-derived therapeutic proteins and their application by direct administration.
Liver Enzymes Abnormalities among Highly Active Antiretroviral Therapy Experienced and HAART Naïve HIV-1 Infected Patients at Debre Tabor Hospital, North West Ethiopia: A Comparative Cross-Sectional Study
Authors: Shiferaw Melashu Balew , Tulu Ketema Tafess , Zegeye Amtatachew Moges , Wubante Amarech Asratie
Published: July 2016

Liver disease has emerged as the most common non-AIDS-related cause of death in HIV patients. However, there is limited data regarding this condition including our setting in Ethiopia. Hence, liver enzyme abnormalities among highly active antiretroviral therapy (HAART) experienced and HAART naïve patients were assessed in this study. A total of 164 HAART experienced and 164 HAART naïve patients were studied. Blood specimen was collected to determine alanine aminotransferase (ALT) and aspartate aminotransferase (AST), CD4 count, and viral hepatitis. The prevalence of liver enzyme abnormality was 20.1% and 22.0% among HAART experienced and HAART naïve patients, respectively. The HAART experienced patients had higher mean ALT than HAART naïve patients (P=0.002). Viral hepatitis (AOR = 6.02; 95% CI = 1.87–19.39), opportunistic infections (AOR = 2.91; 95% CI = 1.04–8.19), current CD4 count <200 cells/mm3(AOR = 2.16; 95% CI = 1.06–4.39), and male sex (AOR = 1.83; 95% CI = 1.001–3.33) were associated with elevated ALT and/or AST. In conclusion, liver enzyme abnormalities were high in both HAART experienced and HAART naïve HIV-1 infected patients. Hence, monitoring and management of liver enzyme abnormalities in HIV-1 infected patients are important in our setting.
Informed Principal Model and Contract in Supply Chain with Demand Disruption Asymmetric Information
Authors: Zhang Huan , Jiang Jianli
Published: July 2016

Because of the frequency and disastrous influence, the supply chain disruption has caused extensive concern both in the industry and in the academia. In a supply chain with one manufacturer and one retailer, the demand of the retailer is uncertain and meanwhile may suffer disruption with a probability. Taking the demand disruption probability as the retailer’s asymmetric information, an informed principal model with the retailer as the principal is explored to make the contract. The retailer can show its information to the manufacturer through the contract. It is found out that the high-risk retailer intends to pretend to be the low-risk one. So the separating contract is given through the low-information-intensity allocation, in which the order quantity and the transferring payment for the low-risk retailer distort upwards, but those of high-risk retailer do not distort. In order to reduce the signaling cost which the low-risk retailer pays, the interim efficient model is introduced, which ends up with the order quantity and transferring payment distorting upwards again but less than before. In the numerical examples, with two different mutation probabilities, the informed principal contracts show the application of the informed principal model in the supply chain with demand disruption.
High Dose Rate Brachytherapy as a Treatment Option in Endobronchial Tumors
Authors: Hosni Ali , Bezjak Andrea , Rink Alexandra , Czarnecka Kasia , McPartlin Andrew , Patterson Susan , Saibishkumar Elantholiparameswaran
Published: July 2016

Purpose. To report our experience with high dose rate endobronchial brachytherapy (HDR-EBBT) and to assess its efficacy and tolerability with possibility of its use in selected cases with curative intent.Method. Retrospective review of patients with endobronchial tumors treated at our institution in 2007–2013 with HDR-EBBT. Subjective response and treatment related toxicity were extracted from patients’ records. Clinical response was evaluated by chest CT +/− bronchoscopy 2-3 months after treatment. Local control (LC) and overall survival (OS) were analyzed.Results. Overall 23 patients were identified. Ten patients were treated with curative intent, in 8 of them HDR-EBBT was combined with external beam radiotherapy. Short term palliation was as follows: dyspnea (13/15), cough (12/14), and hemoptysis (3/3). Seventeen patients were evaluated, of whom 9 (53%) showed complete response. Four patients developed local failure (only 1 of them treated with curative intent) and were salvaged with HDR-EBBT (n=1), chemotherapy (n=2), and laser (n=1). Among patients treated with curative intent, the 2-year LC and OS were 89% and 67%, respectively, and 2 out of 4 deaths were cancer-related. Late toxicity included bronchial stenosis (n=1). Only 1 patient had fatal hemoptysis and postmortem examination indicated local recurrence.Conclusion. HDR-EBBT is promising treatment with tolerable complication if used in properly selected patients.
Machine Learning Approach to Automated Quality Identification of Human Induced Pluripotent Stem Cell Colony Images
Authors: Joutsijoki Henry , Haponen Markus , Rasku Jyrki , Aalto-Setälä Katriina , Juhola Martti
Published: July 2016

The focus of this research is on automated identification of the quality of human induced pluripotent stem cell (iPSC) colony images. iPS cell technology is a contemporary method by which the patient’s cells are reprogrammed back to stem cells and are differentiated to any cell type wanted. iPS cell technology will be used in future to patient specific drug screening, disease modeling, and tissue repairing, for instance. However, there are technical challenges before iPS cell technology can be used in practice and one of them is quality control of growing iPSC colonies which is currently done manually but is unfeasible solution in large-scale cultures. The monitoring problem returns to image analysis and classification problem. In this paper, we tackle this problem using machine learning methods such as multiclass Support Vector Machines and several baseline methods together with Scaled Invariant Feature Transformation based features. We perform over 80 test arrangements and do a thorough parameter value search. The best accuracy (62.4%) for classification was obtained by using ak-NN classifier showing improved accuracy compared to earlier studies.
Propofol Infusion Syndrome in Refractory Status Epilepticus: A Case Report and Topical Review
Authors: Walli Akil , Poulsen Troels Dirch , Dam Mette , Børglum Jens
Published: July 2016

Propofol infusion syndrome (PRIS) is a fatal complication when doses of propofol administration exceed 4 mg/kg/h for more than 48 hours. Propofol overdosage is not uncommon in patients with refractory status epilepticus (RSE). We describe a case of refractory status epilepticus complicated by propofol infusion syndrome and collect from 5 databases all reports of refractory status epilepticus cases that were treated by propofol and developed the syndrome and outline whether refractory status epilepticus treatment with propofol is standardized according to international recommendations, compare it with alternative medications, and discuss how this syndrome can be treated and prevented. A total of 21 patients who developed this syndrome reported arrhythmia in all cases (100%), rhabdomyolysis in 9 cases (42%), lactic acidosis in 13 cases (62%), renal failure in 8 cases (38%), lipemia in 7 cases (33%), and elevated hepatic enzymes in 6 cases (28%). 13 patients died (66%). Propofol is still given in a dosage higher than what is internationally recommended, and new treatment modalities such as renal replacement therapy, blood exchange, and extracorporeal membrane oxygenation seem to be promising. In conclusion, propofol should be carefully titrated, the maximal infusion rate needs to be reassessed, and combination of different sedative agents may be considered.
Structural Damping Effects on Dynamic Instability of Subtangentially Loaded and Shear Deformable Beck’s Columns
Authors: Min Dong-Ju , Park Jaegyun , Yeon Sang-Ho , Kim Moon-Young
Published: July 2016

A frequency equation of externally and internally damped and shear-flexible cantilever columns subjected to a subtangentially follower force is analytically derived in a dimensionless form with relation to the linear instability theory of Beck’s columns. Some parametric studies are then performed with variation of two damping coefficients under the assumption of Rayleigh damping. Based on the analysis results, it is demonstrated that three damping cases in association with flutter loads of Beck’s columns can be selected including one case representative of structural damping. Finally, stability maps of shear-flexible and damped Beck’s columns are constructed for the three damping cases and discussed in the practical range of damping coefficients and shear parameters. In addition, flutter loads and time history analysis results are presented using dimensionless FE analysis and compared with exact solutions.
Effects of Different Montmorillonite Nanoclay Loading on Cure Behavior and Properties of Diglycidyl Ether of Bisphenol A Epoxy
Authors: Tcherbi-Narteh Alfred , Hosur Mahesh , Jeelani Shaik
Published: July 2016

The primary focus of this study was to understand the effects of different amounts of montmorillonite nanoclay (MMT) loading on viscosity, cure behavior, reaction mechanism, and properties of diglycidyl ether of bisphenol A (DGEBA) epoxy composites. Influence of 1–3 wt.% MMT on rheological and subsequent cure behavior of SC-15 epoxy resin was studied using nonisothermal and isothermal rheometry and differential scanning calorimetry (DSC). Rheological properties were influenced by different amounts of MMT at lower shear rates prior to and during curing. Cure reaction mechanism was unaffected by different MMT concentration; however heat and activation energy of reactions increased with increasing MMT loading. Samples with 2 wt.% MMT showed highest reaction rate constant, indicative of catalytic behavior. X-ray diffraction (XRD) and transmission electron microscope (TEM) revealed mainly intercalated microstructure throughout the MMT infused epoxy composite samples irrespective of the percent loading.
Determination of Optimal Opening Scheme for Electromagnetic Loop Networks Based on Fuzzy Analytic Hierarchy Process
Authors: Li Yang , Li Yahui , Han Zijiao , Li Guoqing , Gao Kai , Wang Zhenhao
Published: July 2016

Studying optimization and decision for opening electromagnetic loop networks plays an important role in planning and operation of power grids. First, the basic principle of fuzzy analytic hierarchy process (FAHP) is introduced, and then an improved FAHP-based scheme evaluation method is proposed for decoupling electromagnetic loop networks based on a set of indicators reflecting the performance of the candidate schemes. The proposed method combines the advantages of analytic hierarchy process (AHP) and fuzzy comprehensive evaluation. On the one hand, AHP effectively combines qualitative and quantitative analysis to ensure the rationality of the evaluation model; on the other hand, the judgment matrix and qualitative indicators are expressed with trapezoidal fuzzy numbers to make decision-making more realistic. The effectiveness of the proposed method is validated by the application results on the real power system of Liaoning province of China.
The Use of Xpert MTB/Rif for Active Case Finding among TB Contacts in North West Province, South Africa
Authors: Lebina Limakatso , Fuller Nigel , Osoba Tolu , Scott Lesley , Motlhaoleng Katlego , Rakgokong Modiehi , Abraham Pattamukkil , Variava Ebrahim , Martinson Neil Alexander
Published: July 2016

Introduction.Tuberculosis is a major cause of morbidity and mortality especially in high HIV burden settings. Active case finding is one strategy to potentially reduce TB disease burden. Xpert MTB/Rif has recently been recommended for diagnosis of TB.Methods.Pragmatic randomized trial to compare diagnosis rate and turnaround time for laboratory testing for Xpert MTB/Rif with TB microscopy and culture in household contacts of patients recently diagnosed with TB.Results.2464 household contacts enrolled into the study from 768 active TB index cases. 1068 (44%) were unable to give sputum, but 24 of these were already on TB treatment. 863 (53%) participants sputum samples were tested with smear and culture and 2.7% (23/863; CI: 1.62–3.78) were diagnosed with active TB. Xpert MTB/Rif was used in 515 (21%) participants; active TB was diagnosed in 1.6% (8/515; CI: 0.52–2.68).Discussion and Conclusions.Additional 31 cases were diagnosed with contact tracing of household members. When Xpert MTB/Rif is compared with culture, there is no significant difference in diagnostic yield.
Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance
Authors: Chen Jing , Zhang Jiakui , Li Xin , Zhang Chundong , Zhang Hongbin , Jin Junzhe , Dai Dongqiu
Published: July 2016

A disintegrin and metallopeptidase with thrombospondin motif type 8 (ADAMTS8), a member of the ADAMTS family, was discovered as a novel angiogenesis inhibitor. We analyzed the expression and methylation of ADAMTS8 in primary gastric tumors and gastric cancer cell lines. We also examined the relationship between ADAMTS8 expression and methylation and clinicopathologic features. The results showed that the significant downregulation of ADAMTS8 mRNA expression was observed in gastric cancer cell lines and tissues, and its expression was related to invasive depth and lymph node metastasis. CpG was hypermethylated in gastric cancer cell lines MKN45, MGC803, and BGC823, as well as primary gastric cancer specimens. ADAMTS8 mRNA expression was significantly lower in methylated primary gastric tumors. A significant association was found between ADAMTS8 methylation status and lymph node metastasis in primary gastric cancer. Moreover, ADAMTS8 expression was upregulated in the gastric cancer cell lines MGC803, BGC823, and MKN45 after treatment with 5-aza-2′-deoxycytidine. Thus, our results demonstrate that expression of ADAMTS8 mRNA is significantly decreased and DNA methylation is frequent in gastric cancer. ADAMTS8 hypermethylation is associated with decreased expression in gastric cancer and may play an important role in the invasion and metastasis of gastric cancer.
Miconia sp. Increases mRNA Levels of PPAR Gamma and Inhibits Alpha Amylase and Alpha Glucosidase
Authors: Ortíz-Martinez David Mizael , Rivas-Morales Catalina , de la Garza-Ramos Myriam Angelica , Verde-Star Maria Julia , Nuñez-Gonzalez Maria Adriana , Leos-Rivas Catalina
Published: July 2016

Diabetes mellitus is a public health problem worldwide. For this reason, ethanolic extract of Miconia sp. from Oaxaca, Mexico, was selected in search of an alternative against this disease. The effect of Miconia sp. on mRNA expression of PPARγ on cell line 3T3‐L1, its effect on alpha amylase and alpha glucosidase, lipid accumulation during adipogenesis, and cell viability on VERO cells were evaluated. The mRNA levels of PPARγ increased on 1.393 ± 0.008 folds, lipid accumulation was increased by 29.55% with Miconia sp. extract and 34.57% with rosiglitazone, and α‐amylase and α‐glycosidase were inhibited with IC50 values from 28.23 ± 2.15 μg/mL and 1.95 ± 0.15 μg/mL, respectively; the IC50 on antiproliferative activity on VERO cells was 314.54 ± 45.40 μg/mL. In case of α‐amylase and α‐glycosidase assays, IC50 (inhibitory concentration 50) refers to necessary extract amounts to inhibit 50% of enzymatic activity. On the other hand, on antiproliferative activity, IC50 (inhibitory concentration 50) refers to necessary extract amounts to inhibit 50% of cell proliferation. It was concluded that the compounds present in Miconia sp. ethanolic extract increase mRNA expression of PPARγ, inhibit α‐amylase and α‐glucosidase, and increase lipid accumulation. It constitutes an alternative as adjuvant in diabetes mellitus treatment; therefore, we recommend continuing identifying the compounds responsible for its promising in vivo antidiabetic activity.
Edge Detection from RGB-D Image Based on Structured Forests
Authors: Zhang Heng , Wen Zhenqiang , Liu Yanli , Xu Gang
Published: July 2016

This paper looks into the fundamental problem in computer vision: edge detection. We propose a new edge detector using structured random forests as the classifier, which can make full use of RGB-D image information from Kinect. Before classification, the adaptive bilateral filter is used for the denoising processing of the depth image. As data sources, information of 13 channels from RGB-D image is computed. In order to train the random forest classifier, the approximation measurement of the information gain is used. All the structured labels at a given node are mapped to a discrete set of labels using the Principal Component Analysis (PCA) method. NYUD2 dataset is used to train our structured random forests. The random forest algorithm is used to classify the RGB-D image information for extracting the edge of the image. In addition to the proposed methodology, the quantitative comparisons of different algorithms are presented. The results of the experiments demonstrate the significant improvements of our algorithm over the state of the art.
A Correlation Based Strategy for the Acceleration of Nonlocal Means Filtering Algorithm
Authors: Zhang Junfeng , Wu Jiasong , Coatrieux Jean-Louis , Luo Limin , Chen Yang
Published: July 2016

Although the nonlocal means (NLM) algorithm takes a significant step forward in image filtering field, it suffers from a high computational complexity. To deal with this drawback, this paper proposes an acceleration strategy based on a correlation operation. Instead of per-pixel processing, this approach performs a simultaneous calculation of all the image pixels with the help of correlation operators. Complexity analysis and experimental results are reported and show the advantage of the proposed algorithm in terms of computation and time cost.
Kilonova/Macronova Emission from Compact Binary Mergers
Authors: Tanaka Masaomi
Published: July 2016

We review current understanding of kilonova/macronova emission from compact binary mergers (mergers of two neutron stars or a neutron star and a black hole). Kilonova/macronova is emission powered by radioactive decays ofr-process nuclei and it is one of the most promising electromagnetic counterparts of gravitational wave sources. Emission from the dynamical ejecta of ~0.01M⊙is likely to have a luminosity of ~1040–1041 erg s−1with a characteristic timescale of about 1 week. The spectral peak is located in red optical or near-infrared wavelengths. A subsequent accretion disk wind may provide an additional luminosity or an earlier/bluer emission if it is not absorbed by the precedent dynamical ejecta. The detection of near-infrared excess in short GRB 130603B and possible optical excess in GRB 060614 supports the concept of the kilonova/macronova scenario. At 200 Mpc distance, a typical peak brightness of kilonova/macronova with0.01M⊙ejecta is about 22 mag and the emission rapidly fades to >24 mag within ~10 days. Kilonova/macronova candidates can be distinguished from supernovae by (1) the faster time evolution, (2) fainter absolute magnitudes, and (3) redder colors. Since the high expansion velocity (v~0.1–0.2c) is a robust outcome of compact binary mergers, the detection of smooth spectra will be the smoking gun to conclusively identify the gravitational wave source.
An Efficient Technique for Hardware/Software Partitioning Process in Codesign
Authors: Mhadhbi Imene , Ben Othman Slim , Ben Saoud Slim
Published: July 2016

Codesign methodology deals with the problem of designing complex embedded systems, where automatic hardware/software partitioning is one key issue. The research efforts in this issue are focused on exploring new automatic partitioning methods which consider only binary or extended partitioning problems. The main contribution of this paper is to propose a hybrid FCMPSO partitioning technique, based on Fuzzy C-Means (FCM) and Particle Swarm Optimization (PSO) algorithms suitable for mapping embedded applications for both binary and multicores target architecture. Our FCMPSO optimization technique has been compared using different graphical models with a large number of instances. Performance analysis reveals that FCMPSO outperforms PSO algorithm as well as the Genetic Algorithm (GA), Simulated Annealing (SA), Ant Colony Optimization (ACO), and FCM standard metaheuristic based techniques and also hybrid solutions including PSO then GA, GA then SA, GA then ACO, ACO then SA, FCM then GA, FCM then SA, and finally ACO followed by FCM.
Space Vector Modulation Technique for 3-Level NPC Converter with Constant Switching Frequency
Authors: Ouerdani Imen , Ben Abdelghani Hafedh , Bennani Ben Abdelghani Afef , Montesinos-Miracle Daniel , Slama-Belkhodja Ilhem
Published: July 2016

This paper presents a simple Space Vector Modulation (SVM) methodology for a three-level NPC converter. Nearest three vectors (NTV) and corresponding duty cycles are deduced through simple generic mathematical expressions. Extra degrees of freedom of NPC converter are used to fully benefit from SVM advantages and to control the switching frequency. Simulation and experimental results are presented and discussed to validate the proposed methodology.