bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between impaired adipogenesis of retroperitoneal adipose tissue and hypertrophic obesity: role of endogenous glucocorticoid excess
Authors: Zubiría María G. , Vidal‐Bravo Juana , Spinedi Eduardo , Giovambattista Andrés
Published: June 2014

Although the pro‐adipogenic effect of glucocorticoid (GC) on adipose tissue (AT) precursor cell differentiation is openly accepted, the effect of chronically high peripheral levels of GC on AT mass expansion is not fully understood. In the present study, we aim to assess the in vitro adipogenic capacity of AT precursor cells isolated from retroperitoneal (RP) AT pads of the hypercorticosteronaemic, adult neonatally treated monosodium L‐glutamate (MSG) male rat. To ascertain this issue, we explored the in vitro adipogenic process of stromal‐vascular fraction (SVF) cells isolated from RPAT pads of 60‐day‐old MSG rats. The data recorded indicated that RPAT‐SVF cells from hypercorticosteronaemic MSG rats, although displaying an enhanced proliferation capacity, differentiated slower than normal cells. This dysfunction was associated with a reduction in key parameters indicative of precursor cell commitment, differentiation capacity and the percentage of fully differentiated adipocytes, with a retarded maturation process. The distorted adipogenic capacity was highly conditioned by RPAT‐SVF cells displaying a low committed population and both excessive and reduced expression of anti‐ (Pref‐1 and Wnt‐10b) and pro‐adipogenic (mineralocorticoid receptor) signals respectively. Notably, the normalization of peripheral corticosterone levels in MSG rats, as a result of bilateral adrenalectomy combined with GC replacement therapy, fully prevented reduced RPAT precursor cell commitment and overall impaired adipogenesis. Our study strongly supports that the impaired adipogenic process observed in the adult hypertrophic obese MSG male rat is a GC‐dependent mechanism, thus explaining the unhealthy RPAT expansion observed in human hypertrophic obese phenotypes, such as in the Cushing's syndrome.
Scanning electron microscope evidence of telocytes in vasculature
Authors: Li Hua , Lu Shanshan , Liu Hongnian , Ge Junbo , Zhang Hongqi
Published: June 2014

Here, we here present scanning electron microscope data for the existent telocytes (TCs) on the endothelial surface of the wall of pig coronary arteries, internal thoracic arteries and carotid arteries. These cells have a small (8.39 ± 1.97 μm/4.95 ± 0.91 μm) cell body of different shapes (from round to triangular, depending on the number of cellular prolongations) with very long (of about 30 μm) and thin cellular processes called telopodes (Tps), which have uneven calibre. The number of Tps ranges between 2 and 6. Tps typically present the alternation of podoms and podomers, and also have a dichotomic branching pattern. These data could influence the current attempts for elucidating the role(s) of TCs.
Can we continue to neglect genomic variation in introgression rates when inferring the history of speciation? A case study in aMytilushybrid zone
Authors: Roux C. , Fraïsse C. , Castric V. , Vekemans X. , Pogson G. H. , Bierne N.
Published: June 2014

The use of molecular data to reconstruct the history of divergence and gene flow between populations of closely related taxa represents a challenging problem. It has been proposed that the long‐standing debate about the geography of speciation can be resolved by comparing the likelihoods of a model of isolation with migration and a model of secondary contact. However, data are commonly only fit to a model of isolation with migration and rarely tested against the secondary contact alternative. Furthermore, most demographic inference methods have neglected variation in introgression rates and assume that the gene flow parameter (Nm) is similar among loci. Here, we show that neglecting this source of variation can give misleading results. We analysed DNA sequences sampled from populations of the marine mussels,Mytilus edulisandM. galloprovincialis,across a well‐studied mosaic hybrid zone inEurope and evaluated various scenarios of speciation, with or without variation in introgression rates, using anApproximateBayesianComputation (ABC) approach. Models with heterogeneous gene flow across loci always outperformed models assuming equal migration rates irrespective of the history of gene flow being considered. By incorporating this heterogeneity, the best‐supported scenario was a long period of allopatric isolation during the first three‐quarters of the time since divergence followed by secondary contact and introgression during the last quarter. By contrast, constraining migration to be homogeneous failed to discriminate among any of the different models of gene flow tested. Our simulations thus provide statistical support for the secondary contact scenario in the EuropeanMytilushybrid zone that the standard coalescent approach failed to confirm. Our results demonstrate that genomic variation in introgression rates can have profound impacts on the biological conclusions drawn from inference methods and needs to be incorporated in future studies.
Icariin Combined with Breviscapine Improves the Erectile Function of Spontaneously Hypertensive Rats
Authors: Li Yongxian , Jiang Jun , He Yanzheng , Jiang Rui , Liu Junxiang , Fan Zhongcai , Cheng Yong
Published: June 2014

Introduction

The impaired erectile response in spontaneously hypertensive rats (SHR) is caused by increased signaling of RhoA/Rho-kinase and decreased signaling of nitric oxide (NO). Icariin improves erectile function via upregulating multitargets in NO/cyclic guanosine monophosphate (NO/cGMP) pathway, which breviscapine accomplishes by downregulating RhoA/Rho-kinase pathway.

Aim

To investigate the effect and mechanism of icariin combined with breviscapine on the erectile function of SHR.

Methods

Five 12-week-old male Wistar-Kyoto (WKY) rats and 20 age-matched male SHR were evenly randomized into WKY rats control group, SHR control group, icariin-treated group, breviscapine-treated group, and combined treatment group treated by vehicle, icariin, breviscapine, and icariin plus breviscapine, respectively, by gavage for four successive weeks. Maximum intracavernosal pressure/mean arterial pressure (ICPmax/MAP) and the expression of endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), phosphodiesterase type 5 inhibitors (PDE5), and Rho-associated, coiled-coil containing protein kinase 1 and 2 (ROCK1 and ROCK2) in the cavernous tissues were determined.

Results

The ICPmax/MAP in the combined treatment group was significantly increased compared with SHR control group, icariin-treated group, and breviscapine-treated group. The expression of eNOS and nNOS was significantly higher in the combined treatment group than in SHR control group, icariin-treated group, and breviscapine-treated group (P < 0.05). The expression of PDE5 was significantly lower in the icariin-treated group than in SHR control group (P < 0.05). The expression of ROCK1 was significantly lower in the combined treatment group than in other groups (P < 0.05). The expression of ROCK2 was significantly higher in SHR control group than in WKY rats control group, icariin-treated group, and combined treatment group (P < 0.05). Among these groups, the expression of eNOS and nNOS was the strongest, and ROCK1 was the lowest in WKY rats control group.

Conclusion

Icariin combined with breviscapine has synergistic effects on erectile function of SHR through different signal pathways.
Investigation of cutting methods for small samples of Hayabusa and future sample return missions
Authors: Uesugi Masayuki , Noguchi Ryo , Matsumoto Tooru , Matsuno Junya , Nagano Takashi , Tsuchiyama Akira , Harada Shigenori , Yokoyama Kaori , Yodo Yoshiaki , Takeda Noboru , Yada Toru , Yakame Shogo , Karouji Yuzuru , Ishibashi Yukihiro , Abe Masanao , Okada Tatsuaki , Fujimura Akio , Ebihara Mitsuru , Kitajima Fumio , Nagao Keisuke , Nakamura Tomoki , Naraoka Hiroshi , Noguchi Takaaki , Okazaki Ryuji , Yurimoto Hisayoshi
Published: June 2014

We report the investigation of cutting methods for Hayabusa samples. The purpose of our study is to explore the possibility of applying multiple analyses to a single particle effectively. We investigated the cutting performance of a blade dicing saw, laser, focused ion beam (FIB), and physical breaking by microindenter. Cutting performance was examined by estimating the aspect ratio of the cut slit, i.e., depth over width of the slit. We also investigated the possible contamination and sample damage by cutting. The result of the investigation shows that we can cut the samples from <50 μm to 500 μm using those methods with aspect ratios from 10 to 20, although they would introduce some contamination or damage to the samples. Our investigations also provide an important basis for the analysis of samples obtained by future sample return missions.
Pasinetti after Sen: Towards a Capability Approach to Structural Dynamics of Consumption
Authors: Mori Kenji , Tamate Shintaro
Published: June 2014

Pasinetti's theory of structural dynamics has, as well as the capability approach, normative implications about income distribution and economic growth. Compared with the latter, however, the individual character of consumption is rather neglected in Pasinetti's framework, but the macro‐economic viability is examined here more intensively as a main issue. In this paper, we will show it possible and fruitful to consistently integrate both complementary approaches and present an analytical foundation of a normative theory of the structural dynamics of consumption.
Antibiotics in the first week of life is a risk factor for allergic rhinitis at school age
Authors: Alm Bernt , Goksör Emma , Pettersson Rolf , Möllborg Per , Erdes Laslo , Loid Petra , Åberg Nils , Wennergren Göran
Published: June 2014

Background

Heredity as well as external factors influences the development of allergic rhinitis. The aim of this study was to analyse early risk factors and protective factors for allergic rhinitis at school age.

Methods

This is a prospective, longitudinal study of children born in western Sweden in 2003 where 50% of the birth cohort was randomly selected. The parents answered questionnaires at 6 months, 12 months, 4.5 yr and 8 yr. At 8 yr, 5044 questionnaires were distributed. Of these, 4051 responded, that is, 80.3%. Current allergic rhinitis was defined as symptoms and use of medication during the past 12 months.

Results

Current allergic rhinitis at 8 yr was reported by 10.9%. Mean onset age was 5.7 yr, and 61.9% were boys. In a multivariate analysis, antibiotics in the first week of life increased the risk of allergic rhinitis (adjusted odds ratio 1.75, 95% confidence interval (1.03, 2.97)). Increased risk was also seen with parental allergic rhinitis (aOR 2.73 (2.12, 3.52)), food allergy first year (aOR 2.45 (1.61, 3.73)), eczema first year (aOR 1.97 (1.50, 2.59)) and male gender (aOR 1.35 (1.05, 1.74)). Living on a farm at 4.5 yr reduced the risk (aOR 0.31 (0.13, 0.78)).

Conclusion

Antibiotics in the first week of life increased the risk of allergic rhinitis at school age, while living on a farm at preschool age reduced the risk. Both findings are compatible with the hygiene hypothesis.
The potential for the Farman entrainer to be used with a pediatric t‐piece: a bench study
Authors: Bell Graham T. , Baker Angela , Jamieson Patrick , Kapatuka Kenneth
Published: June 2014

Objectives

To determine the limits of performance of the Farman Entrainer used with the t‐piece for pediatric anesthesia in areas with limited oxygen supplies.

Methods

Bench tests were conducted with different system configurations, normal and ‘emergency situation’ ventilation patterns were replicated to reproduce a range of circumstances the anesthetist may encounter.

Results

We found that Fi02 rises and flow decreases with increasing CPAP, but probably within safe limits. A one way valve is essential to avoid high concentration of volatile agent. Very high ventilation rates reduce flow significantly. Increasing oxygen input from an oxygen concentrator increases the flow output but does not increase Fi02.

Conclusion

The basic characteristics of the system are within normally accepted parameters for t‐piece anesthesia, safety in practice requires to be demonstrated by a clinical study.
Neonatal intubation with direct laryngoscopy vs videolaryngoscopy: an extremely premature baboon model
Authors: Moreira Alvaro , Koele‐Schmidt Lindsey , Leland Michelle , Seidner Steven , Blanco Cynthia
Published: June 2014

Objective

To compare the ability to successfully intubate extremely preterm baboons using conventional direct laryngoscopy (DL) vs videolaryngoscopy.

Methods

A prospective randomized crossover study using experienced and inexperienced neonatal intubators. All participants were shown an educational video on intubation with each device, followed by attempt of the procedure. The time for successful intubation was the primary outcome.

Results

Seven subjects comprised the experienced group, while 10 individuals were in the inexperienced group. The overall intubation success rate was comparable between both devices (53% vs 26%, P = 0.09); however, mean time to intubate with the conventional laryngoscope was faster (25.5 vs 39.4 s, P = 0.02). Although both groups intubated faster with DL, it only reached statistical significance in the inexperienced group (27.0 vs 48.7 s, P < 0.05).

Conclusion

Conventional DL and videolaryngoscopy are suitable modes for intubating extremely preterm baboons. Although experienced intubators prefer DL, intubation success rate and time to intubate with both devices were comparable. In inexperienced intubators, participants preferred and intubated faster with DL.
EZH2: an emerging role in melanoma biology and strategies for targeted therapy
Authors: Tiffen Jessamy , Gallagher Stuart J. , Hersey Peter
Published: June 2014

Histone modifications are increasingly being recognized as important epigenetic mechanisms that govern chromatin structure and gene expression. EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2), responsible for tri‐methylation of lysine 27 on histone 3 (H3K27me3) that leads to gene silencing. This highly conserved histone methyltransferase is found to be overexpressed in many different types of cancers including melanoma, where it is postulated to abnormally repress tumor suppressor genes. Somatic mutations have been identified in approximately 3% of melanomas, and activating mutations described within the catalytic SET domain of EZH2 confer its oncogenic activity. In the following review, we discuss the evidence that EZH2 is an important driver of melanoma progression and we summarize the progress of EZH2 inhibitors against this promising therapeutic target.
5‐Aminolevulinic acid‐Loaded Fullerene Nanoparticles for In Vitro and In Vivo Photodynamic Therapy
Authors: Li Zhi , Pan Li‐Li , Zhang Fei‐Long , Zhu Xia‐Li , Liu Yang , Zhang Zhen‐Zhong
Published: June 2014

This report explores some properties of 80–200 nm nanoparticles containing 5‐aminolevulinic acid (ALA) and fullerene (C60) for photodynamic therapy (PDT). Compared with ALA, the nanoparticles yielded more protoporphyrin IX (PpIX) formation in cells and tissues and to a significant improvement in antitumor efficacy in tumor‐bearing mice. Maximum levels of PpIX were obtained 4 h after administration and selective PpIX formation in tumor was observed. These nanoparticles appear to be a useful vehicle for drug delivery purposes. In this study, a procedure for preparing fullerene nanoparticles containing ALA was developed. The product alone exhibited no detectable toxicity in the dark and was superior to ALA alone in promoting PpIX biosynthesis and PDT efficacy both in culture and in a murine tumor model. These results suggest that this procedure could be the basis for an improved PDT protocol for cancer control.
Short‐term UV‐B Dose Stimulates Production of Protective Metabolites in Matricaria chamomilla Leaves
Authors: Petruľová Veronika , Dučaiová Zuzana , Repčák Miroslav
Published: June 2014

Physiological response of two cultivars of Matricaria chamomilla plants on UV irradiation was studied. The impact of used short‐time UV dose was evaluated in three time points; 2, 24 and 48 h after irradiation. Used UV irradiation immediately resulted in changes in plant oxidative status monitored as increased concentration of H2O2. Decrease in chlorophyll a and b indicated the impact on photosynthetic apparatus. For phenolic secondary metabolites, an increase in total soluble phenols and AlCl3‐reactive flavonols was observed. The activity of main phenolic enzyme, phenylalanine ammonia‐lyase, increased with time after irradiation. Significant changes, mainly decreasing trends, in the content of free coumarins and their glycosidic precursors were observed. Enhanced accumulation in chlorogenic and 1,5‐dicaffeoylquinic acid and in (Z)‐isoform of dicycloethers was detected. From these results, the redirecting precursors of coumarin biosynthesis to biosynthesis of substances with higher antioxidative potential can be assumed. Different reactions in diploid and tetraploid plants were recorded, too.
A Multilevel Modelling Approach to Measuring Changing Patterns of Ethnic Composition and Segregation Among London Secondary Schools, 2001–2010
Authors: Leckie George , Goldstein Harvey
Published: June 2014

Multilevel binomial logistic regression has recently been proposed for the special case of statistically modelling changing composition and segregation of two groups of individuals over two occasions among organizational units, enabling inferences to be made about the underlying social processes which generate these patterns. A simulation method can then be used to re-express the model parameters in the metric of any desired two-group segregation index. We generalize this combined modelling and simulation approach by proposing multilevel random-coefficient multinomial logistic regression for the general case of statistically modelling multiple groups of individuals over multiple occasions and multiple organizational scales. We illustrate this combined approach with an application to modelling changing three-group white–black–Asian ethnic composition and segregation among London secondary schools and local authorities during the first decade of the 21st century.
Outdoor pedestrian fall‐related injuries among Swedish senior citizens – injuries and preventive strategies
Authors: Gyllencreutz Lina , Björnstig Johanna , Rolfsman Ewa , Saveman Britt‐Inger
Published: June 2014

Senior citizens get around, to a large extent, as pedestrians, and safe walking is desirable for senior citizens allowing them to stay mobile, independent and healthy in old age. Senior citizens are over‐represented in injury statistics, and fall‐related injuries are common. The aim of this study was to investigate fall‐related injuries including healthcare costs among senior citizen pedestrians injured when walking in public outdoor environments and to describe their self‐reported causes and suggested preventive strategies. The data were based on a combination of information from injury data and a questionnaire. Three hundred senior citizens attended one emergency department after sustaining injuries from pedestrian falls; 60% suffered nonminor injuries, mostly fractures. One‐fifth of the pedestrians were hospitalised for an average of 8 days with an indirect hospital cost of 6.2 million EUR (55 million SEK). Environmental factors such as ice were the most commonly described cause of the injury incident. Forty per cent of the respondents indicated that the municipality was responsible for the cause of the injury incident. Fewer respondents mentioned their own responsibility as a preventive strategy. Thirty per cent described a combination of improvements such as better road maintenance, changes in human behaviour and use of safety products as preventive strategies. It is of great importance to highlight general safety, products and preventive strategies to minimise injury risks, so that pedestrians can safely realise the known health benefits of walking and thereby limit healthcare costs.
The Learning Rural Area Framework: A Heuristic Tool to Investigate Institutional Arrangements which Support Collaboration in Rural Areas
Authors: Wellbrock Wiebke , Roep Dirk
Published: June 2014

Place‐based approaches to rural development require the collaboration of public and private actors. Such collaboration may be stimulated through joint learning and innovation processes which are supported by various institutional arrangements. There is, however, reason to question the effectiveness of existing institutional arrangements. The learning rural area framework is introduced as a tool to map, analyse and evaluate the operational features of (institutional) arrangements supporting joint learning and innovation in rural areas. Its application is discussed with reference to the Westerkwartier in the Netherlands and other rural areas. It will be shown how the framework can serve as an interactive tool to enhance joint reflexivity, facilitate wider collaboration and help build collective agency. Its potential as a tool for designing and implementing more effective institutional arrangements, catalysing institutional reform and bringing about more collaborative modes of governance should be further explored.
Isolation of the Lateral Border Recycling Compartment Using a Diaminobenzidine‐Induced Density Shift
Authors: Sullivan David P. , Rüffer Claas , Muller William A.
Published: June 2014

The migration of leukocytes across the endothelium and into tissue is critical to mounting an inflammatory response. The lateral border recycling compartment (LBRC), a complex vesicular‐tubule invagination of the plasma membrane found at endothelial cell borders, plays an important role in this process. Although a few proteins have been shown to be present in the LBRC, no unique marker is known. Here, we detail methods that can be used to characterize a subcellular compartment that lacks an identifying marker. Initial characterization of the LBRC was performed using standard subcellular fractionation with sucrose gradients and took advantage of the observation that the compartment migrated at a lower density than other membrane compartments. To isolate larger quantities of the compartment, we modified a classic technique known as a diaminobenzidine (DAB)‐induced density shift. The DAB‐induced density shift allowed for specific isolation of membranes labeled with horseradish peroxidase‐conjugated antibody. Because the LBRC could be differentially labeled at 4°C and 37°C, we were able to identify proteins that are enriched in the compartment, despite lacking a unique marker. These methods serve as a model to others studying poorly characterized compartments and organelles and are applicable to a wide variety of biological systems.
High‐density lipoprotein 3 and apolipoprotein A‐I alleviate platelet storage lesion and release of platelet extracellular vesicles
Authors: Pienimaeki‐Roemer Annika , Fischer Astrid , Tafelmeier Maria , Orsó Evelyn , Konovalova Tatiana , Böttcher Alfred , Liebisch Gerhard , Reidel Armin , Schmitz Gerd
Published: June 2014

Background

Stored platelet (PLT) concentrates (PLCs) for transfusion develop a PLT storage lesion (PSL), decreasing PLT viability and function with profound lipidomic changes and PLT extracellular vesicle (PL‐EV) release. High‐density lipoprotein 3 (HDL3) improves PLT homeostasis through silencing effects on PLT activation in vivo. This prompted us to investigate HDL3 and apolipoprotein A‐I (apoA‐I) as PSL‐antagonizing agents.

Study Design and Methods

Healthy donor PLCs were split into low‐volume standard PLC storage bags and incubated with native (n)HDL3 or apoA‐I from plasma ethanol fractionation (precipitate IV) for 5 days under standard blood banking conditions. Flow cytometry, Born aggregometry, and lipid mass spectrometry were carried out to analyze PL‐EV release, PLT aggregation, agonist‐induced PLT surface marker expression, and PLT and plasma lipid compositions.

Results

Compared to control, added nHDL3 and apoA‐I significantly reduced PL‐EV release by up to −62% during 5 days, correlating with the added apoA‐I concentration. At the lipid level, nHDL3 and apoA‐I antagonized PLT lipid loss (+12%) and decreased cholesteryl ester (CE)/free cholesterol (FC) ratios (−69%), whereas in plasma polyunsaturated/saturated CE ratios increased (+3%) and CE 16:0/20:4 ratios decreased (−5%). Administration of nHDL3 increased PLT bis(monoacylglycero)phosphate/phosphatidylglycerol (+102%) and phosphatidic acid/lysophosphatidic acid (+255%) ratios and improved thrombin receptor–activating peptide 6–induced PLT aggregation (+5%).

Conclusion

nHDL3 and apoA‐I improve PLT membrane homeostasis and intracellular lipid processing and increase CE efflux, antagonizing PSL‐related reduction in PLT viability and function and PL‐EV release. We suggest uptake and catabolism of nHDL3 into the PLT open canalicular system. As supplement in PLCs, nHDL3 or apoA‐I from Fraction IV of plasma ethanol fractionation have the potential to improve PLC quality to prolong storage.
Improving cord blood unit quantity and quality at King Abdullah International Medical Research Center Cord Blood Bank
Authors: Jawdat Dunia , Arab Suha , Thahery Hadeel , Almashaqbeh Walid , Alaskar Ahmed , Hajeer Ali H.
Published: June 2014

Background

Public cord blood banks (CBBs) store cord blood unit (CBU) donations for anyone in need. However, strict regulations need to be followed to build up high‐quality bank products that can be used worldwide. We established a public CBB at a tertiary hospital in Saudi Arabia. Here, we investigated the reasons behind rejecting or not collecting CBUs over 2 years (2011‐2012) and which steps were implemented to improve the number and quality of storable units.

Study Design and Methods

A total of 2891 mothers were evaluated. Reasons for rejecting donors, not collecting, and rejecting units before or after collection were analyzed and compared for the years 2011 and 2012.

Results

A total of 1157 (40%) CBUs were not collected, mainly due to staff availability, and 564 (20%) CBUs were rejected. The main reason for rejecting donations was the mother's or neonate's health. Rejecting CBUs after collection was due to low volume. A total of 1170 (40%) CBUs were successfully collected for potential banking and sent for processing; however, 58% were rejected in the laboratory due to low total nucleated cell counts. Several changes were implemented during the 2 years including physician education and awareness, in utero collection, cesarean collection, and staff recruitment. These changes positively affected the numbers of our collected units. Out of the initially eligible mothers in 2011, only 17% were banked; this was increased to 33% in 2012.

Conclusions

We identified the problems with collecting CBUs for banking and will keep improving our selection process of recruiting more CBUs of high quality.
The -cyclic McKay correspondence via motivic integration
Authors: Yasuda Takehiko
Published: June 2014

We study the McKay correspondence for representations of the cyclic group of order $p$ in characteristic $p$. The main tool is the motivic integration generalized to quotient stacks associated to representations. Our version of the change of variables formula leads to an explicit computation of the stringy invariant of the quotient variety. A consequence is that a crepant resolution of the quotient variety (if any) has topological Euler characteristic $p$ as in the tame case. Also, we link a crepant resolution with a count of Artin–Schreier extensions of the power series field with respect to weights determined by ramification jumps and the representation.
SUMO1 enhances cAMP‐dependent exocytosis and glucagon secretion from pancreatic α‐cells
Authors: Dai Xiao‐Qing , Spigelman Aliya F. , Khan Shara , Braun Matthias , Manning Fox Jocelyn E. , MacDonald Patrick E.
Published: June 2014

Key points

SUMOylation is the reversible modification of proteins by the attachment of small ubiquitin‐like modifier (SUMO) peptides, which in pancreatic β‐cells inhibits insulin exocytosis and glucagon‐like peptide‐1 (GLP‐1) receptor signalling.

We find in glucagon‐secreting pancreatic α‐cells that SUMOylation increases excitability and enhances exocytosis by increasing L‐type Ca2+ currents.

The ability of SUMOylation to facilitate α‐cell exocytosis is cAMP‐dependent, leading to enhanced adrenaline‐stimulated glucagon secretion.

SUMO1 prevents inhibition of α‐cell Na+ current and exocytosis by a GLP‐1 receptor agonist, but does not prevent GLP‐1 receptor‐dependent inhibition of glucagon secretion.

SUMOylation modifies α‐cell responses to cAMP‐dependent signalling and, by contrast with its inhibitory effects in β‐cells, enhances α‐cell exocytosis and glucagon secretion.

Post‐translational modification by the small ubiquitin‐like modifier‐1 (SUMO1) limits insulin secretion from β‐cells by inhibiting insulin exocytosis and glucagon‐like peptide‐1 (GLP‐1) receptor signalling. The secretion of glucagon from α‐cells is regulated in a manner opposite to that of insulin; it is inhibited by elevated glucose and GLP‐1, and increased by adrenergic signalling. We therefore sought to determine whether SUMO1 modulates mouse and human α‐cell function. Action potentials (APs), ion channel function and exocytosis in single α‐cells from mice and humans, identified by glucagon immunostaining, and glucagon secretion from intact islets were measured. The effects of SUMO1 on α‐cell function and the respective inhibitory and stimulatory effects of exendin 4 and adrenaline were examined. Upregulation of SUMO1 increased α‐cell AP duration, frequency and amplitude, in part as a result of increased Ca2+ channel activity that led to elevated exocytosis. The ability of SUMO1 to enhance α‐cell exocytosis was cAMP‐dependent and resulted from an increased L‐type Ca2+ current and a shift away from exocytosis dependent on non‐L‐type channels, an effect that was mimicked by knockdown of the deSUMOylating enzyme sentrin/SUMO‐specific protease‐1 (SENP1). Finally, although SUMO1 prevented GLP‐1 receptor‐mediated inhibition of α‐cell Na+ channels and single‐cell exocytosis, it failed to prevent the exendin 4‐mediated inhibition of glucagon secretion. Consistent with its cAMP dependence, however, SUMO1 enhanced α‐cell exocytosis and glucagon secretion stimulated by adrenaline. Thus, by contrast with its inhibitory role in β‐cell exocytosis, SUMO1 is a positive regulator of α‐cell exocytosis and glucagon secretion under conditions of elevated cAMP.
Hearing in noisy environments: noise invariance and contrast gain control
Authors: Willmore Ben D. B. , Cooke James E. , King Andrew J.
Published: June 2014

Contrast gain control has recently been identified as a fundamental property of the auditory system. Electrophysiological recordings in ferrets have shown that neurons continuously adjust their gain (their sensitivity to change in sound level) in response to the contrast of sounds that are heard. At the level of the auditory cortex, these gain changes partly compensate for changes in sound contrast. This means that sounds which are structurally similar, but have different contrasts, have similar neuronal representations in the auditory cortex. As a result, the cortical representation is relatively invariant to stimulus contrast and robust to the presence of noise in the stimulus. In the inferior colliculus (an important subcortical auditory structure), gain changes are less reliably compensatory, suggesting that contrast‐ and noise‐invariant representations are constructed gradually as one ascends the auditory pathway. In addition to noise invariance, contrast gain control provides a variety of computational advantages over static neuronal representations; it makes efficient use of neuronal dynamic range, may contribute to redundancy‐reducing, sparse codes for sound and allows for simpler decoding of population responses. The circuits underlying auditory contrast gain control are still under investigation. As in the visual system, these circuits may be modulated by factors other than stimulus contrast, forming a potential neural substrate for mediating the effects of attention as well as interactions between the senses.
Topological Defects in Two-Dimensional Crystals: The Stress Buildup and Accumulation
Authors: Song Zhigong , Xu Zhiping
Published: June 2014

Topological defects (TDs) arise in the growth process of two-dimensional (2D) materials, as well as after-growth heat treatment or irradiation. Our atomistic simulation results show that their mechanical modulation of material properties can be understood qualitatively through the theory of elasticity. We find that the in-plane lattice distortion and stress induced by experimentally characterized pentagon-heptagon (5|7) pairs or pentagon-octagon-pentagon (5|8|5) triplets can be captured by 2D models of dislocations or disclinations, although the out-of-plane distortion of the lattice reduces stress localization. Lineups of these TDs create nonlocal stress accumulation within a range of ∼10 nm. Interestingly, pileups of 5|7 and 5|8|5 defects show contrasting tensile and compressive buildups, which lead to opposite grain size dependence of the material strength. These findings improve our understandings of the mechanical properties of 2D materials with TDs, as well as the lattice perfection in forming large-scale continuous graphene films.
Some Exact Solutions to Equations of Motion of an Incompressible Second Grade Fluid
Authors: Ullah Saif , Maqbool Irsa
Published: June 2014

In this paper, we derive some exact solutions of the equations governing the steady plane motions of an incompressible second grade fluid. For this purpose, the vorticity and stream functions both are expressed in terms of complex variables and complex functions. The derived solutions represent the flows having streamlines as a family of ellipses, parabolas, concentric circles, and rectangular hyperbolas. Some physical features of the derived solutions are also illustrated by their contour plots.
Observation of the Development of Secondary Features in a Richtmyer–Meshkov Instability Driven Flow
Authors: Bernard Tennille , Randall Truman C. , Vorobieff Peter , Corbin Clint , Wayne Patrick J. , Kuehner Garrett , Anderson Michael , Kumar Sanjay
Published: June 2014

Richtmyer–Meshkov instability (RMI) has long been the subject of interest for analytical, numerical, and experimental studies. In comparing results of experiment with numerics, it is important to understand the limitations of experimental techniques inherent in the chosen method(s) of data acquisition. We discuss results of an experiment where a laminar, gravity-driven column of heavy gas is injected into surrounding light gas and accelerated by a planar shock. A popular and well-studied method of flow visualization (using glycol droplet tracers) does not produce a flow pattern that matches the numerical model of the same conditions, while revealing the primary feature of the flow developing after shock acceleration: the pair of counter-rotating vortex columns. However, visualization using fluorescent gaseous tracer confirms the presence of features suggested by the numerics; in particular, a central spike formed due to shock focusing in the heavy-gas column. Moreover, the streamwise growth rate of the spike appears to exhibit the same scaling with Mach number as that of the counter-rotating vortex pair (CRVP).
Experimental Determination of Liquefied Petroleum Gas–Gasoline Mixtures Knock Resistance
Authors: Pipitone Emiliano , Genchi Giuseppe
Published: June 2014

The results of previous experimental researches showed that great advantages can be achieved, both in terms of fuel consumption and pollutant emissions, in bifuel vehicles by means of the double-fuel combustion, i.e., the simultaneous combustion of gasoline and a gaseous fuel, such as liquefied petroleum gas (LPG) or natural gas (NG). The substantial increase in knock resistance pursued by adding LPG to gasoline, which allowed to maintain an overall stoichiometric proportion with air also at full load, is not documented in the scientific literature and induced the authors to perform a proper experimental campaign. The motor octane number (MON) of LPG–gasoline mixtures has been hence determined on a standard cooperative fuel research (CFR) engine, equipped with a double-fuel injection system in order to realize different proportions between the two fuels and electronically control the overall air–fuels mixture. The results of the measurement show a quadratic dependence of the MON of the mixture as function of the LPG concentration evaluated on a mass basis, with higher increase for the lower LPG content. A good linear relation, instead, has been determined on the basis of the evaluated LPG molar fraction. The simultaneous combustion of LPG and gasoline may become a third operative mode of bifuel vehicles, allowing to optimize fuel economy, performances, and pollutant emissions; turbocharged bifuel engines could strongly take advantage of the knock resistance of the fuels mixture thus adopting high compression ratio (CR) both in pure gas and double-fuel mode, hence maximizing performance and reducing engine size. The two correlations determined in this work, hence, can be useful for the design of future bifuel engines running with knock safe simultaneous combustion of LPG and gasoline.
Low Order Continuum-Based Liquid Sloshing Formulation for Vehicle System Dynamics
Authors: Wang Liang , Jiménez Octavio Jesús R. , Wei Cheng , Shabana Ahmed A.
Published: June 2014

The objective of this investigation is to develop a low order continuum-based liquid sloshing model that can be successfully integrated with multibody system (MBS) algorithms. The liquid sloshing model proposed in this investigation allows for capturing the effect of the distributed inertia and viscosity of the fluid. The fluid viscous forces are defined using the Navier–Stokes equations. In order to demonstrate the use of the approach presented in this study, the assumption of an incompressible Newtonian fluid is considered with a total Lagrangian approach. Fluid properties such as the incompressibility condition are formulated using a penalty method. The low order model that captures the effect of the distributed fluid inertia on the vehicle dynamics is developed in this investigation using the floating frame reference (FFR) formulation. The use of this approach allows for developing an inertia-variant fluid model that accounts for the dynamic coupling between different modes of the fluid displacements. The matrix of position vector gradients and its derivative are formulated using the FFR kinematic description. The position and velocity gradient tensors are used to define the Navier–Stokes stress forces. The proposed liquid sloshing model is integrated with a MBS railroad vehicle model in which the rail/wheel interaction is formulated using a 3D elastic contact formulation that allows for the wheel/rail separation. Several simulation scenarios are used to examine the effect of the distributed liquid inertia on the motion of the railroad vehicle. The results, obtained using the sloshing model, are compared with the results obtained using a rigid body vehicle model. The comparative numerical study presented in this investigation shows that the effect of the sloshing tends to increase the possibility of wheel/rail separation as the forward velocity increases, thereby increasing the possibility of derailments at these relatively high speeds.
Electromagnetomechanical Coupled Vibration Analysis of a Direct-Drive Off-Shore Wind Turbine Generator
Authors: Kirschneck Michael , Rixen Daniel J. , Polinder Henk , van Ostayen Ron A. J.
Published: June 2014

In large direct-drive off-shore wind turbine generators one challenge is to engineer the system to function securely with an air gap length of about a thousandth of the outer rotor diameter. Compared to the large diameter of the generator rotor, the rolling element bearings can only be constructed with a relatively limited size. This makes it challenging to design appropriate constructions able to transmit the large applied magnetic forces encountered in the air gap of direct drive wind turbine generators. Currently, this challenge is met by designing stiff heavy rotors that are able to withstand the forces in the air gap. Incorporating flexibility into the design of the rotor structure can lead to a lighter less expensive rotor. In order to be able to do this the magnetomechanical coupling in the air gap and its effect on the structural dynamics need to be taken into account when predicting the intended flexibility. This paper introduces an approach for a multiphysical modal analysis that makes it possible to predict the dynamics of the strongly coupled magnetomechanical system. The new method is validated using measurements of a simple lab setup. It is then applied to a single-bearing design direct-drive wind turbine generator rotor to calculate the changes of the structural dynamics caused by the electromagnetomechanical coupling.
A Method for Computing the Analytical Solution of the Steady-State Heat Equation in Multilayered Media
Authors: Dülk Ivor , Kovácsházy Tamás
Published: June 2014

The computation of the analytical solution of the steady temperature distribution in multilayered media can become numerically unstable if there are different longitudinal (i.e., the directions parallel to the layers) boundary conditions for each layer. In this study, we develop a method to resolve these computational difficulties by approximating the temperatures at the junctions step-by-step and solving for the thermal field separately in only the single layers. First, we solve a two-layer medium problem and then show that multilayered media can be represented as a hierarchy of two-layered media; thus, the developed method is generalized to an arbitrary number of layers. To improve the computational efficiency and speed, we use varying weighting coefficients during the iterations, and we present a method to decompose the multilayered media into two-layered media. The developed method involves the steady-state solution of the diffusion equation, which is illustrated for 2D slabs using separation of variables (SOV). A numerical example of four layers is also included, and the results are compared to a numerical solution.
Loudness of time-varying stimuli with electric stimulation
Authors: Francart Tom , Innes-Brown Hamish , McDermott Hugh J. , McKay Colette M.
Published: June 2014

McKay, Henshall, Farrell, and McDermott [J. Acoust. Soc. Am. 113, 2054–2063 (2003)] developed a practical method to estimate the loudness of periodic electrical signals presented through a cochlear implant. In the present work, this method was extended to time-varying sounds based on two models of time-varying loudness for normal listeners. To fit the model parameters, loudness balancing data was collected with six cochlear implant listeners. The pulse rate of a modulated pulse train was adjusted to equalize its loudness to a reference stimulus. The stimuli were single-electrode time-limited pulse bursts, repeated at a rate of 50 Hz, with on-times varying between 2 and 20 ms. The parameters of two different models of time-varying loudness were fitted to the results. For each model, parameters defining the time windows over which the electrical pulses contribute to instantaneous loudness were optimized. In each case, a good fit was obtained with the loudness balancing results. Therefore, the practical method was successfully extended to time-varying sounds by combining it with existing models of time-varying loudness for acoustic stimulation.
Using a coherent hydrophone array for observing sperm whale range, classification, and shallow-water dive profiles
Authors: Tran Duong D. , Huang Wei , Bohn Alexander C. , Wang Delin , Gong Zheng , Makris Nicholas C. , Ratilal Purnima
Published: June 2014

Sperm whales in the New England continental shelf and slope were passively localized, in both range and bearing, and classified using a single low-frequency (<2500 Hz), densely sampled, towed horizontal coherent hydrophone array system. Whale bearings were estimated using time-domain beamforming that provided high coherent array gain in sperm whale click signal-to-noise ratio. Whale ranges from the receiver array center were estimated using the moving array triangulation technique from a sequence of whale bearing measurements. Multiple concurrently vocalizing sperm whales, in the far-field of the horizontal receiver array, were distinguished and classified based on their horizontal spatial locations and the inter-pulse intervals of their vocalized click signals. The dive profile was estimated for a sperm whale in the shallow waters of the Gulf of Maine with 160 m water-column depth located close to the array's near-field where depth estimation was feasible by employing time difference of arrival of the direct and multiply reflected click signals received on the horizontal array. By accounting for transmission loss modeled using an ocean waveguide-acoustic propagation model, the sperm whale detection range was found to exceed 60 km in low to moderate sea state conditions after coherent array processing.
A broadband, capacitive, surface-micromachined, omnidirectional microphone with more than 200 kHz bandwidth
Authors: Kuntzman Michael L. , Hall Neal A.
Published: June 2014

A surface micromachined microphone is presented with 230 kHz bandwidth. The structure uses a 2.25 μm thick, 315 μm radius polysilicon diaphragm suspended above an 11 μm gap to form a variable parallel-plate capacitance. The back cavity of the microphone consists of the 11 μm thick air volume immediately behind the moving diaphragm and also an extended lateral cavity with a radius of 504 μm. The dynamic frequency response of the sensor in response to electrostatic signals is presented using laser Doppler vibrometry and indicates a system compliance of 0.4 nm/Pa in the flat-band of the response. The sensor is configured for acoustic signal detection using a charge amplifier, and signal-to-noise ratio measurements and simulations are presented. A resolution of 0.80 mPa/Hz (32 dB sound pressure level in a 1 Hz bin) is achieved in the flat-band portion of the response extending from 10 kHz to 230 kHz. The proposed sensor design is motivated by defense and intelligence gathering applications that require broadband, airborne signal detection.
Acoustic capture-recapture method for towed acoustic surveys of echolocating porpoises
Authors: Kimura Satoko , Akamatsu Tomonari , Dong Lijun , Wang Kexiong , Wang Ding , Shibata Yasutoki , Arai Nobuaki
Published: June 2014

Passive acoustic monitoring for cetaceans mainly employ fixed-location methods or point transect samplings; an acoustic survey from a moving platform to conduct line transects is less common. In this study, acoustic capture–recapture by combining a double-observer method with line transect sampling was performed to observe Yangtze finless porpoises. Two acoustic devices were towed with the distance between them varying 0.5 to 89.5 m. The conditional probabilities that both devices would detect the porpoises within the same time window were calculated. In a 1-s time window, it became smaller as the distance between the devices increased, approaching zero when the distance between them was more than 50 m. It was considered that the devices with less than 50 m distance detected the same signals from the same animals, which means the identical detection. When the distance between them is too great, the recapture rate is reduced and the incidence of false matching may increase. Thus, a separation distance of around 50 m between two devices in acoustic capture–recapture of Yangtze finless porpoises was recommended. Note that the performance of the double detections can change depending on the particular device used and on animal behaviors such as vocalizing interval, ship avoidance.