bluuebunny/crossref_metadata_2025 huggingface dataset:
Analyses of Alternatively Processed Genes in Ciliates Provide Insights into the Origins of Scrambled Genomes and May Provide a Mechanism for Speciation
Authors: Gao Feng , Roy Scott W. , Katz Laura A.
Published: February 2015

Chromosome rearrangements occur in a variety of eukaryotic life cycles, including during the development of the somatic macronuclear genome in ciliates. Previous work on the phyllopharyngean ciliate Chilodonella uncinata revealed that macronuclear β-tubulin and protein kinase gene families share alternatively processed germ line segments nested within divergent regions. To study genome evolution in this ciliate further, we characterized two additional alternatively processed gene families from two cryptic species of the ciliate morphospecies C. uncinata: those encoding histidine acid phosphatase protein (
Hap
) and leishmanolysin family protein (
Lei
). Analyses of the macronuclear
Hap
and
Lei
sequences reveal that each gene family consists of three members in the macronucleus that are marked by identical regions nested among highly divergent regions. Investigation of the micronuclear
Hap
sequences revealed a complex pattern in which the three macronuclear sequences are derived either from a single micronuclear region or from a combination of this shared region recombined with additional duplicate micronuclear copies of
Hap
. We propose a model whereby gene scrambling evolves by gene duplication followed by partial and reciprocal degradation of the duplicate sequences. In this model, alternative processing represents an intermediate step in the evolution of scrambled genes. Finally, we speculate on the possible role of genome architecture in speciation in ciliates by describing what might happen if changes in alternatively processed loci occur in subdivided populations.

IMPORTANCE
  Genome rearrangements occur in a variety of eukaryotic cells and serve as an important mechanism for generating genomic diversity. The unusual genome architecture of ciliates with separate germline and somatic nuclei in each cell, provides an ideal system to study further principles of genome evolution. Previous analyses revealed complex forms of chromosome rearrangements, including gene scrambling and alternative processing of germ line chromosomes. Here we describe more complex rearrangements between germ line and somatic chromosomes than previously seen in alternatively processed gene families. Drawing on the present and previous findings, we propose a model in which alternative processing of duplicated micronuclear regions represents an intermediate stage in the evolution of scrambled genes. Under this model, alternative processing may provide insights into a mechanism for speciation in ciliates. Our data on gene scrambling and alternative processing also enhance views on the dynamic nature of genomes across the eukaryotic tree of life.
Assessing beliefs and risk perceptions on smoking and smoking cessation in immigrant Chinese adult smokers residing in Vancouver, Canada: a cross-sectional study
Authors: FitzGerald J Mark , Poureslami Iraj , Shum Jessica
Published: February 2015

Objectives

We aimed to conduct culturally-based participatory research to assess cultural and belief contexts for smoking behaviours within Mandarin and Cantonese communities. Outcome variables were smoking-related knowledge, smoking patterns, attitudes and beliefs, and perceived barriers and facilitators to successful cessation.

Design

A community-based approach was applied involving smokers, community key-informants and professionals in study design and implementation. Initially, focus groups were conducted and findings were used to develop study instrument. Participants responded once to study questionnaire after informed consent.

Setting

Community based in the Greater Vancouver Area, Canada.

Participants

16 Chinese smokers participated in focus groups and subsequently, 167 current Chinese immigrant (137 males and 30 females) smokers from Mandarin and Cantonese communities, recruited with the help of community agencies and collaborating physicians, were enrolled in a cross-sectional study.

Results

We found that a majority believed smoking was harmful on their health. Younger smokers (<35 years of age) did not mind smoking in front of young children compared to older smokers (≥35 years of age) (p<0.001). People with high school or lower levels of education believed that they would benefit more from smoking than suffering from withdrawal symptoms compared to better educated smokers (p<0.05). Mandarin smokers were significantly more likely to encourage others to quit than Cantonese smokers (p<0.05). Many indicated not receiving adequate support from care providers and lack of access to culturally and linguistically appropriate cessation programmes impacted on their ability to quit smoking.

Conclusions

Our study highlighted the importance of tobacco beliefs and perceptions among Mandarin and Cantonese speaking immigrants with limited access to healthcare information and for younger smokers whose attention to health consequences of smoking may be limited as well. Study participants were generally aware of the health risks and were willing to quit. Access to appropriate cessation programmes would fulfil their willingness.
Loss of GD1-positiveLactobacilluscorrelates with inflammation in human lungs with COPD
Authors: Sze Marc A , Utokaparch Soraya , Elliott W Mark , Hogg James C , Hegele Richard G
Published: February 2015

Objectives

The present study assesses the relationship between contents of GD1 (glycerol dehydratase)-positiveLactobacillus, presence ofLactobacillusand the inflammatory response measured in host lung tissue in mild to moderate chronic obstructive pulmonary disease (COPD). We hypothesise that there will be a loss of GD1 producingLactobacilluswith increasing severity of COPD and that GD1 has anti-inflammatory properties.

Setting

Secondary care, 1 participating centre in Vancouver, British Columbia, Canada.

Participants

74 individuals who donated non-cancerous portions of their lungs or lobes removed as treatment for lung cancer (normal lung function controls (n=28), persons with mild (GOLD 1) (n=21) and moderate (GOLD 2) COPD (n=25)).

Outcome measures

Primary outcome measure was GD1 positivity within each group and whether or not this impacted quantitative histological measures of lung inflammation. Secondary outcome measures includedLactobacilluspresence and quantification, and quantitative histological measurements of inflammation and remodelling in early COPD.

Results

Total bacterial count (p>0.05) and prevalence ofLactobacillus(p>0.05) did not differ between groups. However, the GD1 gene was detected more frequently in the controls (14%) than in either mild (5%) or moderate (0%) COPD (p<0.05) samples. Macrophage and neutrophil volume fractions (0.012±0.005 (mean±SD) vs 0.026±0.017 and 0.005±0.002 vs 0.015±0.014, respectively) in peripheral lung tissue were reduced in samples positive for the GD1 gene (p<0.0035).

Conclusions

A reduction in GD1 positivity is associated with an increased tissue immune inflammatory response in early stage COPD. There is potential forLactobacillusto be used as a possible therapeutic, however, validation of these results need to be completed before an anti-inflammatory role ofLactobacillusin COPD can be confirmed.
Cognitive ability and personality as predictors of participation in a national colorectal cancer screening programme: the English Longitudinal Study of Ageing
Authors: Gale Catharine R , Deary Ian J , Wardle Jane , Zaninotto Paola , Batty G David
Published: February 2015

Background

The English NHS Bowel Cancer Screening Programme has offered biennial faecal occult blood testing to people aged 60–69 years since 2006, and to those aged 60–74 years since 2010. Analysis of the first 2.6 million screening invitations found that 54% of eligible people took up the invitation. The reasons for this low uptake are unclear. We investigated whether participation in screening varies according to cognitive ability and personality.

Methods

Participants were members of The English Longitudinal Study of Ageing. In 2010–2011, respondents were asked about participation in bowel cancer screening, and cognitive ability and the ‘Big Five’ personality traits were assessed. Logistic regression was used to examine the cross-sectional relationships between cognitive ability and personality and screening participation in 2681 people aged 60–75 years who were eligible to have been invited to take part in the UK national screening programme for bowel cancer.

Results

In age-adjusted and sex-adjusted analyses, better cognition and higher conscientiousness were associated with increased participation in cancer screening. ORs (95% CIs) per SD increase were 1.10 (1.03 to 1.18) for cognitive ability and 1.10 (1.01 to 1.19) for conscientiousness. After further adjustment for household wealth and health literacy—shown previously to be associated with participation—these associations were attenuated (ORs were 1.07 (1.00 to 1.15) and 1.07 (0.97 to 1.18), respectively).

Conclusions

We found some indication that better cognitive function and greater conscientiousness may be linked with a slightly increased likelihood of participation in bowel cancer screening. These relationships need investigation in other cohorts of older people.
The mathematical limits of genetic prediction for complex chronic disease
Authors: Keyes Katherine M , Davey Smith George , Koenen Karestan C , Galea Sandro
Published: February 2015

Background

Attempts at predicting individual risk of disease based on common germline genetic variation have largely been disappointing. The present paper formalises why genetic prediction at the individual level is and will continue to have limited utility given the aetiological architecture of most common complex diseases.

Methods

Data were simulated on one million populations with 10 000 individuals in each populations with varying prevalences of a genetic risk factor, an interacting environmental factor and the background rate of disease. The determinant risk ratio and risk difference magnitude for the association between a gene variant and disease is a function of the prevalence of the interacting factors that activate the gene, and the background rate of disease.

Results

The risk ratio and total excess cases due to the genetic factor increase as the prevalence of interacting factors increase, and decrease as the background rate of disease increases. Germline genetic variations have high predictive capacity for individual disease only under conditions of high heritability of particular genetic sequences, plausible only under rare variant hypotheses.

Conclusions

Under a model of common germline genetic variants that interact with other genes and/or environmental factors in order to cause disease, the predictive capacity of common genetic variants is determined by the prevalence of the factors that interact with the variant and the background rate. A focus on estimating genetic associations for the purpose of prediction without explicitly grounding such work in an understanding of modifiable (including environmentally influenced) factors will be limited in its ability to yield important insights about the risk of disease.
Caudal lumbar disc disease presenting as ‘praying position’‐like posture and gait
Authors: Espadas Irene , Chai Orit , Lindley Samantha , Wessmann Annette
Published: February 2015

A 10‐year‐old Border collie and a five‐year‐old Domestic shorthaired cat are reported with a ‘praying’‐like posture as clinical presentation for caudal lumbar disc disease. Neurological examination localised to L6‐S3 spinal cord segments or nerve roots. Advanced diagnostic imaging revealed disc herniations at L7‐S1 vertebrae in the dog and at L6‐L7 vertebrae in the cat. The dog improved significantly with conservative treatment whereas the cat underwent a decompressive dorsal laminectomy followed by complete resolution of his clinical signs. This unusual posture leads to increased space for the cauda equina within the vertebral canal by widening the caudal lumbar intervertebral spaces and thus suspected to alleviate the pain more successfully compared with a normal posture. A ‘praying position’‐like posture has not been reported as a clinical manifestation for caudal lumbar disc disease in a dog and a cat, yet should be considered as a differential diagnosis for this unusual pain relief posture.
Beetroot juice does not enhance altitude running performance in well-trained athletes
Authors: Arnold Josh Timothy , Oliver Samuel James , Lewis-Jones Tammy Maria , Wylie Lee John , Macdonald Jamie Hugo
Published: February 2015

We hypothesized that acute dietary nitrate (NO3–) provided as concentrated beetroot juice supplement would improve endurance running performance of well-trained runners in normobaric hypoxia. Ten male runners (mean (SD): sea level maximal oxygen uptake, 66 (7) mL·kg–1·min−1; 10 km personal best, 36 (2) min) completed incremental exercise to exhaustion at 4000 m and a 10-km treadmill time-trial at 2500 m simulated altitude on separate days after supplementation with ∼7 mmol NO3– and a placebo at 2.5 h before exercise. Oxygen cost, arterial oxygen saturation, heart rate, and ratings of perceived exertion (RPE) were determined during the incremental exercise test. Differences between treatments were determined using means [95% confidence intervals], paired sample t tests, and a probability of individual response analysis. NO3– supplementation increased plasma nitrite concentration (NO3–, 473 (226) nmol·L–1 vs. placebo, 61 (37) nmol·L–1, P < 0.001) but did not alter time to exhaustion during the incremental test (NO3–, 402 (80) s vs. placebo 393 (62) s, P = 0.5) or time to complete the 10-km time-trial (NO3–, 2862 (233) s vs. placebo, 2874 (265) s, P = 0.6). Further, no practically meaningful beneficial effect on time-trial performance was observed as the 11 [–60 to 38] s improvement was less than the a priori determined minimum important difference (51 s), and only 3 runners experienced a “likely, probable” performance improvement. NO3– also did not alter oxygen cost, arterial oxygen saturation, heart rate, or RPE. Acute dietary NO3– supplementation did not consistently enhance running performance of well-trained athletes in normobaric hypoxia.
Cochinchina MomordicaSeed Suppresses Proliferation and Metastasis in Human Lung Cancer Cells by Regulating Multiple Molecular Targets
Authors: Shen Yang , Meng Linyi , Sun Huajun , Zhu Yizhun , Liu Hongrui
Published: February 2015

Cochinchina Momordica Seed, which is the dried ripe seed of Momordica cochinchinensis (Lour.) Spreng, has been used as a mainly anticancer ingredient for many years in China. This study aims at investigating the roles of an ethanol-soluble extract of Cochinchina Momordica Seed (ECMS) in suppressing the proliferation and metastasis of human lung cancer cells, and further elucidating underlying molecular mechanisms. Our researches suggest that ECMS dose-dependently decreased the survival rates of A549 and H1299 cells, and inhibited the migration and invasion in A549 cells. ECMS-induced apoptosis was accompanied by up-regulation of p53, Bax and the down-regulation of Bcl-2, PI-3K/Akt signal pathway, and resulted in the dissipation of mitochondrial membrane potential (ΔΨm) and sequentially activated caspase-3 cascade. Pre-treated with specific inhibitors, LY294002 (PI-3K inhibitor) and BAY11-7082 (NF-κB inhibitor) could enhance the anti-proliferation effects of ECMS on A549 cells. Furthermore, ECMS could increase the level of E-cadherin and decrease of the level of STAT-3 and MMP-2, and scarcely affected the expression of VEGF, and resulted in the inhibition of migration and invasion. Pre-treated with specific inhibitors, WP1066 (STAT-3 inhibitor) and TIMP-2 (MMP-2 inhibitor) could enhance the inhibitory effects of ECMS on migration. In conclusion, the current data demonstrated ECMS inhibited the proliferation of A549 cells by inducing apoptosis, at least partly through the activation of p53 and inactivation of PI-3K/Akt signaling. STAT-3 and MMP-2 pathways may be partly involved in anti-metastasis activities of ECMS. Hence, ECMS might be a promising candidate for the therapy of the non-small cell lung cancer by regulating multiple molecular targets.
Modulational instability and energy localization of twisted DNA with solvent interaction
Authors: Mohamadou Alidou , Toko Donatien , Alim  , Tabi Conrad B. , Kofane Timoleon C.
Published: February 2015

We investigate the generation of soliton-like pulses along a DNA chain which takes into account both torsional and solvent interaction effects. Interactions between neighboring base pairs are described by a twist angle. Twisting is essential in the model to capture the importance of nonlinear effects for the thermodynamical properties. The nonlinear dynamics of the DNA is then modeled in the Hamiltonian approach by the generalized Dauxois–Peyrard–Bishop model (combination of several models). We introduce the generalized discrete nonlinear Schrödinger equation describing the dynamics of modulated wave through the twisted DNA with solvent interaction. The modulational instability is studied and we present an analytical expression for the MI gain to show the effects of twist angle on MI gain spectra as well as on stability diagram. With the increase of the twist angle the MI gain decreases then increases. Some interesting MI phenomena appear with an additional new MI region as the twist angle increases. The instability and stability diagrams are also affected. Numerical simulations are carried out to show the validity of the analytical approach. The result is that the initial wave breaks into a train of ultrashort pulses with repetition rates, which are trapped in some sites. The impact of the twist angle is investigated and we obtain that the twist angle affects the dynamics of stable patterns generated through the molecule. Thereafter, we study energy localization in the framework of twisted DNA with solvent interaction. While the twist angle leads to a stronger localization of energy, the solvent interaction delocalizes energy along the molecule.
Low symmetry phases of(Al, Ga)Sbunder low pressure
Authors: Tahar Belarbi W. , Rouabhia Abdelkarim , Tair F. , Amrani Bouhalouane , Sekkal Nadir
Published: February 2015

The interesting problem of the first phase transition which is induced by pressure in AlSb and GaSb antimonide binaries is revisited. Then, the case of the AlGaSb ternary has been investigated too. The choice of ternary AlGaSb is due to the particular attention which is given actually to it and to the quasi-absence of investigations of the phase transitions in it. We found that low pressures applied to GaSb and AlSb induce transitions from zinc-blende to Imm2 and from zinc-blende to Cmcm, respectively. Our result for AlSb is in agreement with literature, and in the case of GaSb which poses the problem, we find that the Imm2 phase presents a lower total energy than the b-β-Sn phase. For ternaries, the transition is found to be to a phase which is obtained from the Cmcm phases of binaries. Calculations were performed using the plane wave version of the FPLMTO (PLW-FPLMTO) first principle method based on the local density approximation (LDA) and the generalized gradient approximation (GGA96).
Pausing-time distribution of hydrogen diffusion in Gaussian distribution energy
Authors: Hikita Harumi , Morigaki Kazuo
Published: February 2015

The pausing-time distribution of thermal diffusion of hydrogen is analytically shown in the Gaussian density of state. The pausing-time distribution exhibits a log-normal distribution. It has been shown that the pausing-time distribution follows approximately power law, i.e., t-1-α(t: pausing time). The diffusion coefficient of hydrogen is also obtained to be approximately τα-1 (τ: diffusion time). The value of α is the ratio of hydrogen temperature Tr to T2σ, in which T2σ, is a temperature corresponding to 2σ (σ: standard deviation). Finally, Brownian motion is shown to correspond to the case of σ = 0. The width of the energy distribution play an important role in hydrogen diffusion.
CHARACTERIZATION OF PERIODIC CYLINDRICAL SUBSURFACE DEFECTS BY PULSED FLASH THERMOGRAPHY
Authors: DIKIĆ GORAN , TOMIĆ LJUBIŠA , DAMNJANOVIĆ VESNA , MILANOVIĆ BOJAN
Published: February 2015

A characterization of cylindrical periodic subsurface defects of different sizes by means of pulsed thermography is presented in the paper. To ensure a uniform thermal flux distribution, the test samples were heated in lab conditions using two photographic flashes. Surface temperature was intentionally recorded at an angle to the normal of the sample surface. Recorded temperatures were compared with simulated temperatures and the differences in temperature peak values and temperature peak positions were noted. The thermal image was transformed based on known positions of four noncollinear points, in order to cancel out errors resulting from image recording at an angle. The uniformity of surface heating and the effect of the positions of the defects on the results were tested by means of a simulation model. The positions did not affect defect characterization. It was also found that in spite of nonuniform heating, if the reference points were selected properly, the difference in temperature contrast was negligible.
Seismic Behavior of RC Beam to Partially Steel Tubed Concrete (PSTC) Column Joints Under High Axial Load and Cyclic Loading
Authors: Wu Yun Tian , Fu Yu Shan , Dai Chong-Ming
Published: February 2015

A new type of partially steel tubed concrete (PSTC) column is proposed that is suitable to be used in new high rise reinforced concrete (RC) buildings. Three exterior joint specimens consisting of RC beams and PSTC columns and two exterior RC joint specimens were designed and tested under high axial load and cyclic loading to investigate the joint behavior in terms of failure pattern, hysteresis response, deformation, energy dissipation capacity and degradation of strength and stiffness. Test results indicate that the PSTC column can benefit the performance of the joint in terms of strength, ductility and energy dissipation capacity and can partly compensate for the unfavorable effect induced by slab. The strong column–weak beam mechanism can also be ensured in RC beam to PSTC column joint.
Computational comparison of reactions of CS2 with CHX•- (X = F, Cl, and Br): Do F, Cl, and Br substitutions effect differently?
Authors: Liang Junxi , Su Qiong , Zheng Shijie , Yu Jing , Geng Zhiyuan
Published: February 2015

Calculations based on density functional theory (DFT) have been carried out for the gas-phase ion-molecule reactions of CS 2 with CHX •- ( X = F , Cl , and Br ) to investigate the effect of the halogen-substituent on the reaction mechanism. The doublet potential energy surfaces (PESs), involving two striking reaction patterns named by the middle-C attack and the end-S attack in terms of anion attack on the C and S atoms of CS 2, have been explored and characterized in detail. Compared with the results of the end-S attack, reaction with the middle-C attack pattern displays more efficiency on PES. For a given reaction pattern, the reactions of CHCl •- and CHBr •- occur with similar efficiencies and reactivity trends. The CHF •- anion displays remarkably different reactivity, which is traced to its lower electron binding energy and the effect of the electronegative fluorine substituent. This is in good agreement with the experimental observation. According to the property of the product branching ratios in experiment, dynamical effect is used to evaluate the reason that the end-S attack with less energetically favorable obtained in our theoretical studies is comparable to the middle-C attack.
Quantum reading for the practical man
Authors: Dall'Arno Michele
Published: February 2015

Quantum reading is the art of exploiting the quantum properties of light to retrieve classical information stored in an optical memory with low energy and high accuracy. It was shown that the optimal strategy for quantum reading of beamsplitters largely outperforms coherent strategies, further allowing for perfect quantum reading, but requires a source challenging from the experimental viewpoint. Focusing on probes — i.e. BAT states and entangled coherent states (ECS) — which are experimentally feasible with present quantum optical technology, but still allow for perfect quantum reading, we evaluate the tradeoffs between the energy and the probability of error (failure) in ambiguous (unambiguous) quantum reading. It turns out that BAT states outperform ECS in any regime except for the case of high-energy discrimination of two beamsplitters with similar reflectivities.
An online anomaly detection method for stream data using isolation principle and statistic histogram
Authors: Ding Zhiguo , Fei Minrui , Du Dajun
Published: February 2015

Online anomaly detection for stream data has been explored recently, where the detector is supposed to be able to perform an accurate and timely judgment for the upcoming observation. However, due to the inherent complex characteristics of stream data, such as quick generation, tremendous volume and dynamic evolution distribution, how to develop an effective online anomaly detection method is a challenge. The main objective of this paper is to propose an adaptive online anomaly detection method for stream data. This is achieved by combining isolation principle with online ensemble learning, which is then optimized by statistic histogram. Three main algorithms are developed, i.e., online detector building algorithm, anomaly detecting algorithm and adaptive detector updating algorithm. To evaluate our proposed method, four massive datasets from the UCI machine learning repository recorded from real events were adopted. Extensive simulations based on these datasets show that our method is effective and robust against different scenarios.
Improving the Quality of China's Urbanization Through New-Type Urbanization
Authors: LIANG Benfan , CHEN Mengmei
Published: February 2015

Fog and haze have attacked Beijing many times, while the rise in population is causing overcrowding, high housing price, and the concern about environmental problems occur in Beijing, Shanghai, Guangzhou and other cities. What's more, the development of small and medium towns becomes weaker, and the "Dual structure" phenomenon in both between urban and rural areas and within the city is intensified. In this situation, people lose confidence and doubt about the "Urbanization". This paper discusses the scientific connotation of new-type urbanization and puts forward the basic point of improving the quality of China's urbanization through new-type urbanization. This paper is of far-reaching strategic meaning and historical significance for the implementation of new-type urbanization national development planning, as well as the promotion of China's low-carbon ecological civilization construction.
BiFeO3 Thin Films: A Playground for Exploring Electric-Field Control of Multifunctionalities
Authors: Yang Jan-Chi , He Qing , Yu Pu , Chu Ying-Hao
Published: February 2015

A promising approach to the next generation of low-power, functional, and green nanoelectronics relies on advances in the electric-field control of lattice, charge, orbital, and spin degrees of freedom in novel materials. The possibility of electric-field control of these multiple materials functionalities offers interesting options across a range of modern technologies, including information communication, computing processes, data storage, active components, and functional electronics. This article reviews electric-field control and modulation of various degrees of freedom through the medium of multiferroic BiFeO3. Coexisting order parameters and inherent couplings in this materials system form a potent playground, enabling direct and indirect manipulation to obtain intriguing properties and functionalities with an electric stimulus. An in-depth understanding of those electrically controlled phenomena and breakthroughs is highlighted, paving a new route toward multifunctional nanoelectronics. This article concludes with a brief discussion on foreseeable challenges as well as future directions.
Human islet preparations distributed for research exhibit a variety of insulin-secretory profiles
Authors: Kayton Nora S. , Poffenberger Gregory , Henske Joseph , Dai Chunhua , Thompson Courtney , Aramandla Radhika , Shostak Alena , Nicholson Wendell , Brissova Marcela , Bush William S. , Powers Alvin C.
Published: February 2015

Human islet research is providing new insights into human islet biology and diabetes, using islets isolated at multiple US centers from donors with varying characteristics. This creates challenges for understanding, interpreting, and integrating research findings from the many laboratories that use these islets. In what is, to our knowledge, the first standardized assessment of human islet preparations from multiple isolation centers, we measured insulin secretion from 202 preparations isolated at 15 centers over 11 years and noted five distinct patterns of insulin secretion. Approximately three quarters were appropriately responsive to stimuli, but one quarter were dysfunctional, with unstable basal insulin secretion and/or an impairment in stimulated insulin secretion. Importantly, the patterns of insulin secretion by responsive human islet preparations (stable Baseline and Fold stimulation of insulin secretion) isolated at different centers were similar and improved slightly over the years studied. When all preparations studied were considered, basal and stimulated insulin secretion did not correlate with isolation center, biological differences of the islet donor, or differences in isolation, such as Cold Ischemia Time. Dysfunctional islet preparations could not be predicted from the information provided by the isolation center and had altered expression of genes encoding components of the glucose-sensing pathway, but not of insulin production or cell death. These results indicate that insulin secretion by most preparations from multiple centers is similar but that in vitro responsiveness of human islets cannot be predicted, necessitating preexperimental human islet assessment. These results should be considered when one is designing, interpreting, and integrating experiments using human islets.
Fgfr2 is integral for bladder mesenchyme patterning and function
Authors: Walker K. A. , Ikeda Y. , Zabbarova I. , Schaefer C. M. , Bushnell D. , De Groat W. C. , Kanai A. , Bates C. M.
Published: February 2015

While urothelial signals, including sonic hedgehog (Shh), drive bladder mesenchyme differentiation, it is unclear which pathways within the mesenchyme are critical for its development. Studies have shown that fibroblast growth factor receptor (Fgfr)2 is necessary for kidney and ureter mesenchymal development. The objective of the present study was to determine the role of Fgfr2 in the bladder mesenchyme. We used Tbx18cre mice to delete Fgfr2 in the bladder mesenchyme ( Fgfr2 BM−/−). We performed three-dimensional reconstructions, quantitative real-time PCR, in situ hybridization, immunolabeling, ELISAs, immunoblot analysis, void stain on paper, ex vivo bladder sheet assays, and in vivo decerebrated cystometry. Compared with control bladders, embryonic day 16.5 (E16.5) Fgfr2 BM−/− bladders had thin muscle layers with less α-smooth muscle actin and thickened lamina propria with increased collagen type Ia and IIIa that intruded into the muscle. The reciprocal changes in mutant layer thicknesses appeared partly due to a cell fate switch. From postnatal days 1 to 30, Fgfr2 BM−/− bladders demonstrated progressive muscle loss and increased collagen expression. Postnatal Fgfr2 BM−/− bladder sheets exhibited decreased agonist-mediated contractility and increased passive stretch tension versus control bladder sheets. Cystometry revealed high baseline and threshold pressures and shortened intercontractile intervals in Fgfr2 BM−/− versus control bladders. Mechanistically, whereas Shh expression appeared normal, mRNA and protein readouts of hedgehog activity were increased in E16.5 Fgfr2 BM−/− versus control bladders. Moreover, E16.5 Fgfr2 BM−/− bladders exhibited higher levels of Cdo and Boc, hedgehog coreceptors that enhance sensitivity to Shh, compared with control bladders. In conclusion, loss of Fgfr2 in the bladder mesenchyme leads to abnormal bladder morphology and decreased compliance and contractility.
Neurons in cat V1 show significant clustering by degree of tuning
Authors: Ziskind Avi J. , Emondi Al A. , Kurgansky Andrei V. , Rebrik Sergei P. , Miller Kenneth D.
Published: February 2015

Neighboring neurons in cat primary visual cortex (V1) have similar preferred orientation, direction, and spatial frequency. How diverse is their degree of tuning for these properties? To address this, we used single-tetrode recordings to simultaneously isolate multiple cells at single recording sites and record their responses to flashed and drifting gratings of multiple orientations, spatial frequencies, and, for drifting gratings, directions. Orientation tuning width, spatial frequency tuning width, and direction selectivity index (DSI) all showed significant clustering: pairs of neurons recorded at a single site were significantly more similar in each of these properties than pairs of neurons from different recording sites. The strength of the clustering was generally modest. The percent decrease in the median difference between pairs from the same site, relative to pairs from different sites, was as follows: for different measures of orientation tuning width, 29–35% (drifting gratings) or 15–25% (flashed gratings); for DSI, 24%; and for spatial frequency tuning width measured in octaves, 8% (drifting gratings). The clusterings of all of these measures were much weaker than for preferred orientation (68% decrease) but comparable to that seen for preferred spatial frequency in response to drifting gratings (26%). For the above properties, little difference in clustering was seen between simple and complex cells. In studies of spatial frequency tuning to flashed gratings, strong clustering was seen among simple-cell pairs for tuning width (70% decrease) and preferred frequency (71% decrease), whereas no clustering was seen for simple-complex or complex-complex cell pairs.
Bilateral force transients in the upper limbs evoked by single-pulse microstimulation in the pontomedullary reticular formation
Authors: Hirschauer Thomas J. , Buford John A.
Published: February 2015

Neurons in the pontomedullary reticular formation (PMRF) give rise to the reticulospinal tract. The motor output of the PMRF was investigated using stimulus-triggered averaging of electromyography (EMG) and force recordings in two monkeys ( M. fascicularis). EMG was recorded from 12 pairs of upper limb muscles, and forces were detected using two isometric force-sensitive handles. Of 150 stimulation sites, 105 (70.0%) produced significant force responses, and 139 (92.5%) produced significant EMG responses. Based on the average flexor EMG onset latency of 8.3 ms and average force onset latency of 15.9 ms poststimulation, an electromechanical delay of ∼7.6 ms was calculated. The magnitude of force responses (∼10 mN) was correlated with the average change in EMG activity ( P < 0.001). A multivariate linear regression analysis was used to estimate the contribution of each muscle to force generation, with flexors and extensors exhibiting antagonistic effects. A predominant force output pattern of ipsilateral flexion and contralateral extension was observed in response to PMRF stimulation, with 65.3% of significant ipsilateral force responses directed medially and posteriorly ( P < 0.001) and 78.6% of contralateral responses directed laterally and anteriorly ( P < 0.001). This novel approach permits direct measurement of force outputs evoked by central nervous system microstimulation. Despite the small magnitude of poststimulus EMG effects, low-intensity single-pulse microstimulation of the PMRF evoked detectable forces. The forces, showing the combined effect of all muscle activity in the arms, are consistent with reciprocal pattern of force outputs from the PMRF detectable with stimulus-triggered averaging of EMG.
Incorporating 3D-printing technology in the design of head-caps and electrode drives for recording neurons in multiple brain regions
Authors: Headley Drew B. , DeLucca Michael V. , Haufler Darrell , Paré Denis
Published: February 2015

Recent advances in recording and computing hardware have enabled laboratories to record the electrical activity of multiple brain regions simultaneously. Lagging behind these technical advances, however, are the methods needed to rapidly produce microdrives and head-caps that can flexibly accommodate different recording configurations. Indeed, most available designs target single or adjacent brain regions, and, if multiple sites are targeted, specially constructed head-caps are used. Here, we present a novel design style, for both microdrives and head-caps, which takes advantage of three-dimensional printing technology. This design facilitates targeting of multiple brain regions in various configurations. Moreover, the parts are easily fabricated in large quantities, with only minor hand-tooling and finishing required.
Characterization of Toll-Like Receptor-4 (TLR-4) in the Spleen and Thymus of Swiss Albino Mice and Its Modulation in Experimental Endotoxemia
Authors: Ghosh Chandrayee , Bishayi Biswadev
Published: February 2015

Expression of innate immune receptors varies among organs and species and within different strains among the same species; thus, periodic classification of different pattern recognition receptors in the available strains is necessary to initiate different therapeutic approaches to combat inflammation. On characterization of TLR-4 in spleen and thymus of Swiss albino mice—with no reports of TLR-4 expression—induced with endotoxemia, it was found that the mode of expression varied among the organs at both mRNA and protein level in a time-dependent manner. Their functionality was verified by measuring proinflammatory and anti-inflammatory cytokines. In thein vitrostudy using isolated macrophages and lymphocytes from the same organs, the expression of TLR-4 after a shorter period of LPS stimulation was verified. The results substantiated the potent role of macrophage on LPS challenge compared to lymphocytes. The diverse pattern of TLR-4 expression on different cell population indicated their distinct functional activity in LPS-endotoxemia. It may be hypothesized that the expression patterns of TLR-4 could be different based on the anatomical localization and the varying bacterial milieu or bacterial endotoxin encountered in each anatomical location. Thus, blocking TLR-4 or administering IL-6 or IL-10 might impart protection against endotoxemia in the clinical field.
A Structural Optimization Framework for Multidisciplinary Design
Authors: Kurdi Mohammad
Published: February 2015

This work describes the development of a structural optimization framework adept at accommodating diverse customer requirements. The purpose is to provide a framework accessible to the optimization research analyst. The framework integrates the method of moving asymptotes into the finite element analysis program (FEAP) by exploiting the direct interface capability in FEAP. Analytic sensitivities are incorporated to provide a robust and efficient optimization search. User macros are developed to interface the design algorithm and analytic sensitivity with the finite element analysis program. To test the optimization tool and sensitivity calculations, three sizing and one topology optimization problems are considered. In addition, flutter analysis of a heated panel is analyzed as an example of coupling to nonstructural discipline. In sizing optimization, the calculated semianalytic sensitivities match analytic and finite difference calculations. Differences between analytic designs and numerical ones are less than 2.0% and are attributed to discrete nature of finite elements. In the topology problem, quadratic elements are found robust at resolving checkerboard patterns.
Mucolytics for Intubated Asthmatic Children: A National Survey of United Kingdom Paediatric Intensive Care Consultants
Authors: Snoek Aarjan Peter , Brierley Joe
Published: February 2015

Aim. The extent to which mucolytics are utilised in mechanically ventilated asthmatic children is unknown. We sought to establish current practice in the United Kingdom (UK) including choice of mucolytic, dose, and frequency of utilisation.Methods. A national electronic survey was distributed to UK consultants during April and May 2014. We were able to identify 168 PICU consultants at 25 institutions to whom we were able to electronically distribute a survey, representing an estimated 81% of UK NHS PICU consultants.Results. Replies were received from 87 consultants at 21 institutions (response rate=52%). Recombinant human DNase (rhDNase) does get administered by 63% of clinicians, with 54% and 19% that administer hypertonic saline or N-acetylcysteine, respectively. Of those that do administer rhDNase the majority (48%) dilute it with 0.9% saline and blindly administer it, whereas 35% administer rhDNase under bronchoscopic guidance and 17% judge the necessity for bronchoscopy according to clinical severity. 25 respondents described 7 different methods to calculate rhDNase dose. A majority (87%) of respondents expressed an interest to consider enrolling patients into an RCT that evaluates rhDNase.Conclusion. Significant variation exists regarding the necessity for mucolytics, choice of agent, optimal route, and dose in intubated asthmatic children.
Identification of Susceptibility Genes for Peritoneal, Ovarian, and Deep Infiltrating Endometriosis Using a Pooled Sample-Based Genome-Wide Association Study
Authors: Borghese Bruno , Tost Jörg , de Surville Magalie , Busato Florence , Letourneur Frank , Mondon Françoise , Vaiman Daniel , Chapron Charles
Published: February 2015

Characterizing genetic contributions to endometriosis might help to shorten the time to diagnosis, especially in the most severe forms, but represents a challenge. Previous genome-wide association studies (GWAS) made no distinction between peritoneal endometriosis (SUP), endometrioma (OMA), and deep infiltrating endometriosis (DIE). We therefore conducted a pooled sample-based GWAS and distinguished histologically confirmed endometriosis subtypes. We performed an initial discovery step on 10-individual pools (two pools per condition). After quality control filtering, a Monte-Carlo simulation was used to rank the significant SNPs according to the ratio of allele frequencies and the coefficient of variation. Then, a replication step of individual genotyping was conducted in an independent cohort of 259 cases and 288 controls. Our approach was very stringent but probably missed a lot of information due to the Monte-Carlo simulation, which likely explained why we did not replicate results from “classic” GWAS. Four variants (rs227849,rs4703908,rs2479037, andrs966674) were significantly associated with an increased risk of OMA.Rs4703908, located close toZNF366,provided a higher risk of OMA (OR = 2.22; 95% CI: 1.26–3.92) and DIE, especially with bowel involvement (OR = 2.09; 95% CI: 1.12–3.91).ZNF366, involved in estrogen metabolism and progression of breast cancer, is a new biologically plausible candidate for endometriosis.
Controlling Terahertz Surface Plasmon Properties on a Periodically Structured Silicon Surface
Authors: Kumar Gagan
Published: February 2015

The paper presents experimental and numerical investigations on the terahertz (THz) surface plasmon propagation in a periodically patterned doped silicon substrate. Silicon substrates are periodically patterned with 2D array of vertical structures forming a plasmonic waveguide. The waveguide configurations are found to support resonant surface modes at certain frequencies which can occur anywhere depending on the structural parameters. The 2D pattern of vertical structures is observed to affect the THz surface plasmon propagation along the waveguide configuration. The periodicities are changed in both directions to examine the change in amplitude and cut-off frequencies of the resonant surface modes. The results are confirmed independently through finite element method based numerical simulations and compared with theory. The present study should find applications in facilitating the development of futuristic ultrahigh speed networks and devices operating at the terahertz frequencies.
Generalized Runge-Kutta Method with respect to the Non-Newtonian Calculus
Authors: Kadak Uğur , Özlük Muharrem
Published: February 2015

Theory and applications of non-Newtonian calculus have been evolving rapidly over the recent years. As numerical methods have a wide range of applications in science and engineering, the idea of the design of such numerical methods based on non-Newtonian calculus is self-evident. In this paper, the well-known Runge-Kutta method for ordinary differential equations is developed in the frameworks of non-Newtonian calculus given in generalized form and then tested for different generating functions. The efficiency of the proposed non-Newtonian Euler and Runge-Kutta methods is exposed by examples, and the results are compared with the exact solutions.
Posttraumatic Stress and Posttraumatic Stress Disorder after Termination of Pregnancy and Reproductive Loss: A Systematic Review
Authors: Daugirdaitė Viltė , van den Akker Olga , Purewal Satvinder
Published: February 2015

Objective. The aims of this systematic review were to integrate the research on posttraumatic stress (PTS) and posttraumatic stress disorder (PTSD) after termination of pregnancy (TOP), miscarriage, perinatal death, stillbirth, neonatal death, and failed in vitro fertilisation (IVF).Methods. Electronic databases (AMED, British Nursing Index, CINAHL, MEDLINE, SPORTDiscus, PsycINFO, PubMEd, ScienceDirect) were searched for articles using PRISMA guidelines.Results. Data from 48 studies were included. Quality of the research was generally good. PTS/PTSD has been investigated in TOP and miscarriage more than perinatal loss, stillbirth, and neonatal death. In all reproductive losses and TOPs, the prevalence of PTS was greater than PTSD, both decreased over time, and longer gestational age is associated with higher levels of PTS/PTSD. Women have generally reported more PTS or PTSD than men. Sociodemographic characteristics (e.g., younger age, lower education, and history of previous traumas or mental health problems) and psychsocial factors influence PTS and PTSD after TOP and reproductive loss.Conclusions. This systematic review is the first to investigate PTS/PTSD after reproductive loss. Patients with advanced pregnancies, a history of previous traumas, mental health problems, and adverse psychosocial profiles should be considered as high risk for developing PTS or PTSD following reproductive loss.
Design and Synthesis of Pyrazole-3-one Derivatives as Hypoglycaemic Agents
Authors: Datar Prasanna A. , Jadhav Sonali R.
Published: February 2015

Pyrazole-3-one compounds were designed on the basis of docking studies of previously reported antidiabetic pyrazole compounds. The amino acid residues found during docking studies were used as guidelines for the modification of aromatic substitutions on pyrazole-3-one structure. Depending on the docking score, the designed compounds were selectively prioritized for synthesis. The synthesized compounds were subjected to in vivo hypoglycemic activity using alloxan induced diabetic rats and metformin as a standard. Compound 4 having sulphonamide derivative was found to be the most potent compound among the series.