bluuebunny/crossref_metadata_2025 huggingface dataset:
Disruption of Notch signaling aggravates irradiation-induced bone marrow injury, which is ameliorated by a soluble Dll1 ligand through Csf2rb2 upregulation
Authors: Chen Juan-Juan , Gao Xiao-Tong , Yang Lan , Fu Wei , Liang Liang , Li Jun-Chang , Hu Bin , Sun Zhi-Jian , Huang Si-Yong , Zhang Yi-Zhe , Liang Ying-Min , Qin Hong-Yan , Han Hua
Published: May 2016

Physical and chemical insult-induced bone marrow (BM) damage often leads to lethality resulting from the depletion of hematopoietic stem and progenitor cells (HSPCs) and/or a deteriorated BM stroma. Notch signaling plays an important role in hematopoiesis, but whether it is involved in BM damage remains unclear. In this study, we found that conditional disruption of RBP-J, the transcription factor of canonical Notch signaling, increased irradiation sensitivity in mice. Activation of Notch signaling with the endothelial cell (EC)-targeted soluble Dll1 Notch ligand mD1R promoted BM recovery after irradiation. mD1R treatment resulted in a significant increase in myeloid progenitors and monocytes in the BM, spleen and peripheral blood after irradiation. mD1R also enhanced hematopoiesis in mice treated with cyclophosphamide, a chemotherapeutic drug that induces BM suppression. Mechanistically, mD1R increased the proliferation and reduced the apoptosis of myeloid cells in the BM after irradiation. The β chain cytokine receptor Csf2rb2 was identified as a downstream molecule of Notch signaling in hematopoietic cells. mD1R improved hematopoietic recovery through up-regulation of the hematopoietic expression of Csf2rb2. Our findings reveal the role of Notch signaling in irradiation- and drug-induced BM suppression and establish a new potential therapy of BM- and myelo-suppression induced by radiotherapy and chemotherapy.
VEGF-B inhibits hyperglycemia- and Macugen-induced retinal apoptosis
Authors: Huang Delong , Zhao Chen , Ju Rong , Kumar Anil , Tian Geng , Huang Lijuan , Zheng Lei , Li Xianglin , Liu Lixian , Wang Shasha , Ren Xiangrong , Ye Zhimin , Chen Wei , Xing Liying , Chen Qishan , Gao Zhiqin , Mi Jia , Tang Zhongshu , Wang Bin , Zhang Shuping , Lee Chunsik , Li Xuri
Published: May 2016

Vascular endothelial growth factor B (VEGF-B) was discovered a long time ago. However, its role in hyperglycemia- and VEGF-A inhibition-induced retinal apoptosis remains unknown thus far. Yet, drugs that can block VEGF-B are being used to treat patients with diabetic retinopathy and other ocular neovascular diseases. It is therefore urgent to have a better understanding of the function of VEGF-B in these pathologies. Here, we report that both streptozotocin (STZ)-induced diabetes in rats and Macugen intravitreal injection in mice leads to retinal apoptosis in retinal ganglion cell and outer nuclear layers respectively. Importantly, VEGF-B treatment by intravitreal injection markedly reduced retinal apoptosis in both models. We further reveal that VEGF-B and its receptors, vascular endothelial growth factor 1 (VEGFR1) and neuropilin 1 (NP1), are abundantly expressed in rat retinae and choroids and are upregulated by high glucose with concomitant activation of Akt and Erk. These data highlight an important function of VEGF-B in protecting retinal cells from apoptosis induced by hyperglycemia and VEGF-A inhibition. VEGF-B may therefore have a therapeutic potential in treating various retinal degenerative diseases, and modulation of VEGF-B activity in the eye needs careful consideration.
Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction
Authors: Okumura Naoki , Sakamoto Yuji , Fujii Keita , Kitano Junji , Nakano Shinichiro , Tsujimoto Yuki , Nakamura Shin-ichiro , Ueno Morio , Hagiya Michio , Hamuro Junji , Matsuyama Akifumi , Suzuki Shingo , Shiina Takashi , Kinoshita Shigeru , Koizumi Noriko
Published: May 2016

The corneal endothelium maintains corneal transparency; consequently, its dysfunction causes severe vision loss. Tissue engineering-based therapy, as an alternative to conventional donor corneal transplantation, is anticipated to provide a less invasive and more effective therapeutic modality. We conducted a preclinical study for cell-based therapy in a primate model and demonstrated regeneration of the corneal endothelium following injection of cultured monkey corneal endothelial cells (MCECs) or human CECs (HCECs), in combination with a Rho kinase (ROCK) inhibitor, Y-27632, into the anterior chamber. We also evaluated the safety and efficacy of Good Manufacturing Practice (GMP)-grade HCECs, similar to those planned for use as transplant material for human patients in a clinical trial and we showed that the corneal endothelium was regenerated without adverse effect. We also showed that CEC engraftment is impaired by limited substrate adhesion, which is due to actomyosin contraction induced by dissociation-induced activation of ROCK/MLC signaling. Inclusion of a ROCK inhibitor improves efficiency of engraftment of CECs and enables cell-based therapy for treating corneal endothelial dysfunction as a clinically relevant therapy.
Identification and Characterization of Epstein-Barr Virus Genomes in Lung Carcinoma Biopsy Samples by Next-Generation Sequencing Technology
Authors: Wang Shanshan , Xiong Hongchao , Yan Shi , Wu Nan , Lu Zheming
Published: May 2016

Epstein-Barr virus (EBV) has been detected in the tumor cells of several cancers, including some cases of lung carcinoma (LC). However, the genomic characteristics and diversity of EBV strains associated with LC are poorly understood. In this study, we sequenced the EBV genomes isolated from four primary LC tumor biopsy samples, designated LC1 to LC4. Comparative analysis demonstrated that LC strains were more closely related to GD1 strain. Compared to GD1 reference genome, a total of 520 variations in all, including 498 substitutions, 12 insertions and 10 deletions were found. Latent genes were found to harbor the most numbers of nonsynonymous mutations. Phylogenetic analysis showed that all LC strains were closely related to Asian EBV strains, whereas different from African/American strains. LC2 genome was distinct from the other three LC genomes, suggesting at least two parental lineages of EBV among the LC genomes may exist. All LC strains could be classified as China 1 and V-val subtype according to the amino acid sequence of LMP1 and EBNA1, respectively. In conclusion, our results showed the genomic diversity among EBV genomes isolated from LC, which might facilitate to uncover the previously unknown variations of pathogenic significance.
Topical Delivery of Protein and Peptide Using Novel Cell Penetrating Peptide IMT-P8
Authors: Gautam Ankur , Nanda Jagpreet Singh , Samuel Jesse S. , Kumari Manisha , Priyanka Priyanka , Bedi Gursimran , Nath Samir K. , Mittal Garima , Khatri Neeraj , Raghava Gajendra Pal Singh
Published: May 2016

Skin, being the largest organ of the body, is an important site for drug administration. However, most of the drugs have poor permeability and thus drug delivery through the skin is very challenging. In this study, we examined the transdermal delivery capability of IMT-P8, a novel cell-penetrating peptide. We generated IMT-P8-GFP and IMT-P8-KLA fusion constructs and evaluated their internalization into mouse skin after topical application. Our results demonstrate that IMT-P8 is capable of transporting green fluorescent protein (GFP) and proapoptotic peptide, KLA into the skin and also in different cell lines. Interestingly, uptake of IMT-P8-GFP was considerably higher than TAT-GFP in HeLa cells. After internalization, IMT-P8-KLA got localized to the mitochondria and caused significant cell death in HeLa cells signifying an intact biological activity. Further in vivo skin penetration experiments revealed that after topical application, IMT-P8 penetrated the stratum corneum, entered into the viable epidermis and accumulated inside the hair follicles. In addition, both IMT-P8-KLA and IMT-P8-GFP internalized into the hair follicles and dermal tissue of the skin following topical application. These results suggested that IMT-P8 could be a potential candidate to be used as a topical delivery vehicle for various cosmetic and skin disease applications.
Cross-linked Composite Gel Polymer Electrolyte using Mesoporous Methacrylate-Functionalized SiO2 Nanoparticles for Lithium-Ion Polymer Batteries
Authors: Shin Won-Kyung , Cho Jinhyun , Kannan Aravindaraj G. , Lee Yoon-Sung , Kim Dong-Won
Published: May 2016

Liquid electrolytes composed of lithium salt in a mixture of organic solvents have been widely used for lithium-ion batteries. However, the high flammability of the organic solvents can lead to thermal runaway and explosions if the system is accidentally subjected to a short circuit or experiences local overheating. In this work, a cross-linked composite gel polymer electrolyte was prepared and applied to lithium-ion polymer cells as a safer and more reliable electrolyte. Mesoporous SiO2 nanoparticles containing reactive methacrylate groups as cross-linking sites were synthesized and dispersed into the fibrous polyacrylonitrile membrane. They directly reacted with gel electrolyte precursors containing tri(ethylene glycol) diacrylate, resulting in the formation of a cross-linked composite gel polymer electrolyte with high ionic conductivity and favorable interfacial characteristics. The mesoporous SiO2 particles also served as HF scavengers to reduce the HF content in the electrolyte at high temperature. As a result, the cycling performance of the lithium-ion polymer cells with cross-linked composite gel polymer electrolytes employing methacrylate-functionalized mesoporous SiO2 nanoparticles was remarkably improved at elevated temperatures.
Porous anatase TiO2 derived from a titanium metal–organic framework as a multifunctional phospho-oriented nanoreactor integrating accelerated digestion of proteins and in situ enrichment
Authors: Zhao Man , Chen Tianqi , Deng Chunhui
Published: May 2016

Hierarchical porous anatase TiO2 derived from a titanium MOF was synthesized and used as a multifunctional phospho-oriented nanoreactor.
Gadolinium/DOTA functionalized poly(ethylene glycol)-block-poly(acrylamide-co-acrylonitrile) micelles with synergistically enhanced cellular uptake for cancer theranostics
Authors: Tong Guoquan , Fang Zhuangnian , Huang Gang , Jing Yihan , Dai Shulin , Jiang Qing , Zhang Chao , Feng Shi-Ting , Li Zi-Ping
Published: May 2016

The combination of diagnostic and therapeutic functions into a nano-carrier could achieve a delivery system with both accurate diagnosis and delivery capabilities.
Chemical and pharmaceutical evaluation of the relationship between triazole linkers and pore size on cyclodextrin–calixarene nanosponges used as carriers for natural drugs
Authors: Massaro M. , Cinà V. , Labbozzetta M. , Lazzara G. , Lo Meo P. , Poma P. , Riela S. , Noto R.
Published: May 2016

Nanosponges based nanocarriers with three different cavities were used to encapsulate and release bioactive compounds.
Self-assembled structure and relaxation dynamics of diblock copolymers made of polybutadiene and styrene/butadiene rubber
Authors: da Silva C. A. , Budde H. , Menzel M. , Wendler U. , Bartke M. , Weydert M. , Beiner M.
Published: May 2016

Interrelations between self-assembled structure and cooperative α dynamics are systematically studied based on two series of poly(butadiene-block-(styrene-stat-butadiene)) diblock copolymers.
Thinning of n-layer MoS2 by annealing a palladium film under vacuum
Authors: Deng Ya , Chen Minjiang , Zhang Jian , Hu Xiao , Zhao Yun , Nshimiyimana Jean Pierre , Chi Xiannian , Hou Gu , Chu Weiguo , Sun Lianfeng
Published: May 2016

When Pd is thermally evaporated onto n-layer MoS2, a uniform film is formed on the surface.If Pd/n-layer MoS2 is annealed at high temperature in vacuum, thinning of n-layer MoS2 is observed.
CoOx nanoparticles embedded in porous graphite carbon nanofibers derived from electrospun polyacrylonitrile@polypyrrole core–shell nanostructures for high-performance supercapacitors
Authors: Nie Guangdi , Lu Xiaofeng , Chi Maoqiang , Jiang Yanzhou , Wang Ce
Published: May 2016

A novel composite nanostructure of C–CoOx–C with CoOx nanoparticles embedded in N-containing porous graphite carbon nanofibers exhibited a more acceptable specific capacitance, higher rate capability and better cycling stability.
Synthetic m3G-CAP attachment necessitates a minimum trinucleotide constituent to be recognised as a nuclear import signal
Authors: Honcharenko M. , Bestas B. , Jezowska M. , Wojtczak B. A. , Moreno P. M. D. , Romanowska J. , Bächle S. M. , Darzynkiewicz E. , Jemielity J. , Smith C. I. E. , Strömberg R.
Published: May 2016

Minimal requirement for Snurportin based nuclear uptake is the inclusion of a trinucleotide sequence between the m3G-CAP and the artificial linker.
Integrated microfluidic system for cell co-culture and simulation of drug metabolism
Authors: Jie Mingsha , Li Hai-Fang , Lin Luyao , Zhang Jie , Lin Jin-Ming
Published: May 2016

We present a microfluidic integrator for cell cocultivation and simulation of pharmaceutical kinetic processes of oral drugs including intestinal absorption, liver metabolism, and anticancer activity.
Highly active and durable self-standing WS2/graphene hybrid catalysts for the hydrogen evolution reaction
Authors: Zhou Haiqing , Yu Fang , Sun Jingying , He Ran , Wang Yumei , Guo Chuan Fei , Wang Feng , Lan Yucheng , Ren Zhifeng , Chen Shuo
Published: May 2016

Efficient hydrogen evolution catalysts are fabricated by growing WS2 on 3D graphene/Ni foam, featured by large current density (10 mA cm−2 at −119 mV) and low Tafel slope (∼43 mV per dec), outperforming most previous WS2 catalysts.
Nanofluid slip flow over a stretching cylinder with Schmidt and Péclet number effects
Authors: Md Basir Md Faisal , Uddin M. J. , Md. Ismail A. I. , Bég O. Anwar
Published: May 2016

A mathematical model is presented for three-dimensional unsteady boundary layer slip flow of Newtonian nanofluids containing gyrotactic microorganisms over a stretching cylinder. Both hydrodynamic and thermal slips are included. By applying suitable similarity transformations, the governing equations are transformed into a set of nonlinear ordinary differential equations with appropriate boundary conditions. The transformed nonlinear ordinary differential boundary value problem is then solved using the Runge-Kutta-Fehlberg fourth-fifth order numerical method in Maple 18 symbolic software. The effects of the controlling parameters on the dimensionless velocity, temperature, nanoparticle volume fractions and microorganism motile density functions have been illustrated graphically. Comparisons of the present paper with the existing published results indicate good agreement and supports the validity and the accuracy of our numerical computations. Increasing bioconvection Schmidt number is observed to depress motile micro-organism density function. Increasing thermal slip parameter leads to a decrease in temperature. Thermal slip also exerts a strong influence on nano-particle concentration. The flow is accelerated with positive unsteadiness parameter (accelerating cylinder) and temperature and micro-organism density function are also increased. However nano-particle concentration is reduced with positive unsteadiness parameter. Increasing hydrodynamic slip is observed to boost temperatures and micro-organism density whereas it decelerates the flow and reduces nano-particle concentrations. The study is relevant to nano-biopolymer manufacturing processes.
Bi-material crystalline whispering gallery mode microcavity structure for thermo-opto-mechanical stabilization
Authors: Itobe Hiroki , Nakagawa Yosuke , Mizumoto Yuta , Kangawa Hiroi , Kakinuma Yasuhiro , Tanabe Takasumi
Published: May 2016

We fabricated a calcium fluoride (CaF2) whispering gallery mode (WGM) microcavity with a computer controlled ultra-precision cutting process. We observed a thermo-opto-mechanical (TOM) oscillation in the CaF2 WGM microcavity, which may influence the stability of the optical output when the cavity is employed for Kerr comb generation. We studied experimentally and numerically the mechanism of the TOM oscillation and showed that it is strongly dependent on cavity diameter. In addition, our numerical study suggests that a microcavity structure fabricated with a hybrid material (i.e. CaF2 and silicon), which is compatible with an ultra-high Q and high thermal conductivity, will allow us to reduce the TOM oscillation and stabilize the optical output.
Asymptotic Functional Form Preservation Method with Supersymmetric Quantum Mechanics for Anharmonic Oscillators
Authors: Chou Chia-Chun , Li Ching-Teh
Published: May 2016

The asymptotic functional form preservation method is developed in the framework of supersymmetric quantum mechanics to obtain the energies and wave functions of anharmonic oscillators. For each of the ground states in the hierarchy of supersymmetric partner Hamiltonians, we derive a series expansion of the superpotential for . Employing a transformation containing an unphysical parameter, we convert the series expansion of the superpotential into a new series expansion applicable to all the range of x. The unphysical parameter is determined by the principle of minimal sensitivity. Requiring the preservation of the correct asymptotic functional form of the full-range series expansion as x tends to infinity, we obtain the ground and excited state energies. The truncated full-range series expansion for the superpotential provides an approximate analytical expression for the wave function. In addition, several ansatz functional forms are also proposed for the superpotential to obtain the ground and excited state energies with high accuracy. Excellent computational results for the anharmonic oscillator demonstrate that the method proposed here is suitable for solving similar quantum mechanical problems.
The “Necessity” of New Position Limits in Agricultural Futures Markets: The Verdict from Daily Firm‐level Position Data
Authors: Sanders Dwight R. , Irwin Scott H.
Published: May 2016

Regulators are proposing new position limits in U.S. commodity futures markets while the actual impact of long‐only index funds on futures prices continues to be debated. Researchers have noted the data limitations—frequency and market breadth—associated with using data compiled by the U.S. Commodity Futures Trading Commission (CFTC). This research addresses these shortfalls by using daily position data for a specific long‐only index fund. The empirical analysis focuses on the firm‐level position data across 13 U.S. agricultural futures markets. The firm‐level data are shown to be representative of the overall index fund industry. Empirical tests fail to find any evidence linking the firm's trading with market returns. However, there does appear to be a consistent negative relationship between the firm's roll transactions and changes in calendar price spreads. Notably, the direction of this impact runs contrary to the price‐pressure hypothesis. The results of this study, and others, indicate that a clear verdict can be reached—new limits on speculation in agricultural futures markets are unnecessary.
Seed germination of seven desert plants and implications for vegetation
restoration
Authors: Lai Liming , Chen Lijun , Jiang Lianhe , Zhou Jihua , Zheng Yuanrun , Shimizu Hideyuki
Published: May 2016

Germination cues reflect the conditions under which a species is likely to succeed in recruitment. Therefore, knowledge of the seed germination characteristics of key plant species in desertified areas is essential for restoration. The aims of this study were to evaluate the seed germination responses of seven native species, and to explore the implications for vegetation restoration. Seeds of seven desert species were sown in Petri dishes and subjected to various temperature and light conditions. The seeds germinated well at day/night temperatures of 25/15 °C and 30/20 °C but poorly at 35/25 °C. Seeds germinated best in the dark, and final germination percentages of all species were strongly inhibited at a photon irradiance of 1000 µmol m −2 s −1 . Based on these results and the environmental conditions of their natural habitat, Agropyron cristatum and Artemisia halodendron are best adapted to shifting sand dunes: Elymus dahuricus , Caragana korshinskii and C. microphylla for semi-fixed sand dunes: and Medicago sativa and Melilotus suaveolen for fixed sand dunes. If seeds are sown in early May, they will likely be buried in sand, and the precipitation and temperature conditions will be suitable for seedling survival.
Genetic admixture and lineage separation in a southern Andean plant
Authors: Morello Santiago , Sede Silvana M.
Published: May 2016

Mountain uplifts have generated new ecologic opportunities for plants, and triggered evolutionary processes, favouring an increase on the speciation rate in all continents. Moreover, mountain ranges may act as corridors or barriers for plant lineages and populations. In South America a high rate of diversification has been linked to Andean orogeny during Pliocene/Miocene. More recently, Pleistocene glacial cycles have also shaped species distribution and demography. The endemic genus Escallonia is known to have diversified in the Andes. Species with similar morphology obscure species delimitation and plants with intermediate characters occur naturally. The aim of this study is to characterize genetic variation and structure of two widespread species of Escallonia : E. alpina and E. rubra . We analyzed the genetic variation of populations of the entire distribution range of the species and we also included those with intermediate morphological characters; a total of 94 accessions from 14 populations were used for the Amplified Fragment Length Polymorphism (AFLP) analysis. Plastid DNA sequences ( trnS-trnG , 3 ′ trnV-ndhC intergenic spacers and the ndhF gene) from sixteen accessions of Escallonia species were used to construct a Statistical Parsimony network. Additionally, we performed a geometric morphometrics analysis on 88 leaves from 35 individuals of the two E. alpina varieties to further study their differences. Wright’s Fst and analysis of molecular variance tests performed on AFLP data showed a significant level of genetic structure at the species and population levels. Intermediate morphology populations showed a mixed genetic contribution from E. alpina var. alpina and E. rubra both in the Principal Coordinates Analysis (PCoA) and STRUCTURE. On the other hand, E. rubra and the two varieties of E. alpina are well differentiated and assigned to different genetic clusters. Moreover, the Statistical Parsimony network showed a high degree of divergence between the varieties of E. alpina : var. alpina is more closely related to E. rubra and other species than to its own counterpart E. alpina var. carmelitana . Geometric morphometrics analysis (Elliptic Fourier descriptors) revealed significant differences in leaf shape between varieties. We found that diversity in Escallonia species analyzed here is geographically structured and deep divergence between varieties of E. alpina could be associated to ancient evolutionary events like orogeny. Admixture in southern populations could be the result of hybridization at the margins of the parental species’ distribution range.
Top-down analysis of protein samples by de novo sequencing techniques
Authors: Vyatkina Kira , Wu Si , Dekker Lennard J. M. , VanDuijn Martijn M. , Liu Xiaowen , Tolić Nikola , Luider Theo M. , Paša-Tolić Ljiljana , Pevzner Pavel A.
Published: May 2016

Motivation: Recent technological advances have made high-resolution mass spectrometers affordable to many laboratories, thus boosting rapid development of top-down mass spectrometry, and implying a need in efficient methods for analyzing this kind of data.

Results: We describe a method for analysis of protein samples from top-down tandem mass spectrometry data, which capitalizes on de novo sequencing of fragments of the proteins present in the sample. Our algorithm takes as input a set of de novo amino acid strings derived from the given mass spectra using the recently proposed Twister approach, and combines them into aggregated strings endowed with offsets. The former typically constitute accurate sequence fragments of sufficiently well-represented proteins from the sample being analyzed, while the latter indicate their location in the protein sequence, and also bear information on post-translational modifications and fragmentation patterns.

Availability and Implementation: Freely available on the web at http://bioinf.spbau.ru/en/twister.

Contact:  vyatkina@spbau.ru or ppevzner@ucsd.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Cost of Herpes Zoster in Patients With Selected Immune-Compromised Conditions in the United States
Authors: Li Qian , Chen Shih-Yin , Burstin Stuart J. , Levin Myron J. , Suaya Jose A.
Published: May 2016

Background.  This retrospective study investigates the healthcare costs of herpes zoster (HZ) in patients with selected immune-compromised (IC) conditions in the United States (US).

Methods.  Patients with incident HZ diagnosis (index date) were selected from nationwide administrative claims databases from 2005 to 2009. Baseline IC groups, analyzed separately, included adults aged 18–64 years with the following: human immunodeficiency virus infection (HIV), solid organ transplant (SOT), bone marrow or stem cell transplant (BMSCT), or cancer; and older adults (aged ≥65 years) with cancer. Herpes zoster patients (n = 2020, n = 1053, n = 286, n = 13 178, and n = 9089, respectively) were 1-to-1 matched to controls without HZ (with randomly selected index date) in the same baseline group. The healthcare resource utilization and costs (2014 US dollars) during the first 2 postindex quarters were compared between matched cohorts with continuous enrollment during the quarter.

Results.  Herpes zoster patients generally had greater use of inpatient, emergency room and outpatient services, and pain medications than matched controls (P < .05). The incremental costs of HZ during the first postindex quarter were $3056, $2649, $13 332, $2549, and $3108 for HIV, SOT, BMSCT, cancer in adults aged 18–64 years, and cancer in older adults, respectively (each P < .05). The incremental costs of HZ during the second quarter were only significant for adults aged 18–64 years with cancer ($1748, P < .05). The national incremental costs of HZ were projected to be $298 million annually across the 5 IC groups.

Conclusions.  The healthcare cost associated with HZ among patients with studied IC conditions was sizable and occurred mainly during the first 90 days after diagnosis.
Guaiac faecal occult blood screening in individuals younger than 50 years of age
Authors: Zalts Ronen , Moadi Zeid , Avizohar Ophir , Leiba Ronit , Half Elizabeth , Karban Amir
Published: May 2016

To determine the effectiveness of guaiac faecal occult blood tests (gFOBT) in the early detection of colorectal cancer (CRC) within a population of asymptomatic individuals who attended general periodic examinations, and to suggest the recommended age for this screening tool, the electronic database of the periodic examination institute of Rambam Healthcare Campus for the years 2004–2013 was reviewed. Individuals with positive gFOBT results were interviewed for further workup. Proportions of individuals for whom a polyp or CRC was detected were evaluated according to sex and age. 18 858 individuals were examined during the study period, mean age 48 years. The overall gFOBT uptake was 40.8%. Uptake was significantly higher among men and increased with age. Positive gFOBT was detected in 105 individuals (1.4%). The proportion of positive gFOBT was significantly lower among individuals aged 30–50 years than those older than 50 years of age (1.1 and 1.7%, respectively, P=0.005). No positive gFOBT was detected among individuals younger than 30 years of age. Positive gFOBT was higher in men than in women: 1.8 and 0.9% respectively (P=0.002). CRC was detected in six individuals, including two younger than 50 years of age. Polyps were detected in 15 individuals; of these, four were younger than 50 years of age. In the gFOBT-positive group, proportions of polyps and CRC were the same for subgroups according to age. The findings support consideration of annual gFOBT screening from the age of 40 years.
CMX-2043 Mechanisms of Action In Vitro
Authors: Lader Alan S. , Baguisi Alexander , Casale Ralph , Kates Steven A. , Beeuwkes Reinier
Published: May 2016

α-Lipoic acid has been shown to provide cytoprotection in some tissues through antioxidant and antiapoptotic mechanisms. We have enhanced these properties by synthetic modification, resulting in a new chemical entity, CMX-2043, with proven efficacy in an animal model of cardiac ischemia-reperfusion injury. The present studies compare cytoprotective cellular pathways of r-α-lipoic acid and CMX-2043. Biochemical and cellular assays were used to compare antioxidant potency, tyrosine kinase activation, and protein kinase B (Akt) phosphorylation. CMX-2043 was more effective than lipoic acid in antioxidant effect, activation of insulin receptor kinase, soluble tyrosine kinase, and Akt phosphorylation. Activation of insulin-like growth factor 1 receptor was similar for both. CMX-2043 stimulation of Akt phosphorylation was abolished by the phosphatidylinositide 3-kinase inhibitor LY294002. Consistent with Akt activation, CMX-2043 reduced carbachol-induced calcium overload. The s-stereoisomer of CMX-2043 was less active in the biochemical assays than the r-isomer. These results are consistent with cytoprotection through activation of Akt and antioxidant action. CMX-2043 may thus provide a pharmacological approach to cytoprotection consistent with established anti-apoptotic mechanisms.
VERSE: a versatile and efficient RNA-Seq read counting tool
Authors: Zhu Qin , Fisher Stephen A , Shallcross Jamie , Kim Junhyong
Published: May 2016

Motivation

RNA-Seq is a powerful technology that delivers digital gene expression data. To measure expression strength at the gene level, one popular approach is direct read counting after aligning the reads to a reference genome/transcriptome. HTSeq is one of the most popular ways of counting reads, yet its slow running speed of poses a bottleneck to many RNA-Seq pipelines. Gene level counting programs also lack a robust scheme for quantifying reads that map to non-exonic genomic features, such as intronic and intergenic regions, even though these reads are prevalent in most RNA-Seq data.

Results

In this paper we present VERSE, an RNA-Seq read counting tool which builds upon the speed of featureCounts and implements the counting modes of HTSeq. VERSE is more than 30x faster than HTSeq when computing the same gene counts. VERSE also supports a hierarchical assignment scheme, which allows reads to be assigned uniquely and sequentially to different types of features according to user-defined priorities.

Availability

VERSE is implemented in C. It is built on top of featureCounts. VERSE is open source and can be downloaded freely from Github (https://github.com/qinzhu/VERSE).

Contact

junhyong@sas.upenn.edu

Supplementary information

Tables and figures illustrating the counting modes implemented in VERSE and the differences between hierarchical and independent assignment.
RefSoil: A reference database of soil microbial genomes
Authors: Choi Jinlyung , Yang Fan , Stepanauskas Ramunas , Cardenas Erick , Garoutte Aaron , Williams Ryan , Flater Jared , Tiedje James M , Hofmockel Kirsten S. , Gelder Brian , Howe Adina
Published: May 2016

A database of curated genomes is needed to better assess soil microbial communities and their processes associated with differing land management and environmental impacts. Interpreting soil metagenomic datasets with existing sequence databases is challenging because these datasets are biased towards medical and biotechnology research and can result in misleading annotations. We have curated a database of 922 genomes of soil-associated organisms (888 bacteria and 34 archaea). Using this database, we evaluated phyla and functions that are enriched in soils as well as those that may be underrepresented in RefSoil. Our comparison of RefSoil to soil amplicon datasets allowed us to identify targets that if cultured or sequenced would significantly increase the biodiversity represented within RefSoil. To demonstrate the opportunities to access these underrepresented targets, we employed single cell genomics in a pilot experiment to sequence 14 genomes. This effort demonstrates the value of RefSoil in the guidance of future research efforts and the capability of single cell genomics as a practical means to fill the existing genomic data gaps.
Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study
Authors: Wu Joseph T. , Peak Corey M. , Leung Gabriel M. , Lipsitch Marc
Published: May 2016

Background

The ongoing yellow fever (YF) epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa in July-August 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidating the conditions under which dose fractionation would reduce transmission.

Methods

We estimate the effective reproductive number for YF in Angola using disease natural history and case report data. With simple mathematical models of YF transmission, we calculate the infection attack rate (IAR, the proportion of population infected over the course of an epidemic) under varying levels of transmissibility and five-fold fractional-dose vaccine efficacy for two vaccination scenarios: (i) random vaccination in a hypothetical population that is completely susceptible; (ii) the Kinshasa vaccination campaign in July-August 2016 with different age cutoff for fractional-dose vaccines.

Findings

We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (i.e. a proportion VE of vaccinees receives complete and the remainder receive no protection),n-fold fractionation can dramatically reduce IAR as long as efficacy VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (i.e. the susceptibility of each vaccinee is reduced by a factor that is equal to the vaccine efficacy VE). The age cutoff for fractional-dose vaccines chosen by the WHO for the Kinshasa vaccination campaign (namely, 2 years) provides the largest reduction in IAR if the efficacy of five-fold fractional-dose vaccines exceeds 20%.

Interpretation

Dose fractionation is a very effective strategy for reducing infection attack rate that would be robust with a large margin for error in case fractional-dose VE is lower than expected.

Funding

NIH-MIDAS, HMRF-Hong Kong
Higher classification sensitivity of short metagenomic reads with CLARK-S
Authors: Ounit Rachid , Lonardi Stefano
Published: May 2016

The growing number of metagenomic studies in medicine and environmental sciences is creating increasing demands on the computational infrastructure designed to analyze these very large datasets. Often, the construction of ultra-fast and precise taxonomic classifiers can compromise on their sensitivity (i.e., the number of reads correctly classified). Here we introduce CLARK-S, a new software tool that can classify short reads with high precision, high sensitivity and high speed at the same time.
Further evidence on idiosyncratic risk and REIT pricing: a cross-country analysis
Authors: Mi Lin , Benson Karen , Faff Robert
Published: May 2016

Purpose

The purpose of this study is to provide new cross-country evidence on the relation between real estate investment trust (REIT) returns and idiosyncratic risk for samples of listed and unlisted REITs in the US and Australia.

Design/methodology/approach

Five alternative models with exponential GARCH enhancements were employed, in a Fama-MacBeth (1973) setup. The authors assess the statistical significance of the idiosyncratic risk variable and interpret the outcomes.

Findings

The results show that listed REITs in the US and Australia demonstrate a positive idiosyncratic risk-return linkage over the long period of January 1980-November 2013 and April 1994-December 2012, respectively. A further examination by sub-period reveals that this positive relation is only evident in the new REIT era (January 1993-September 2001), absent in the vintage era (before December 1992) and maturity era (November 2001-August 2008). The unlisted REITs in both countries show no relation with idiosyncratic risk. Further, the global financial crisis has no effect on the relation between idiosyncratic risk and REIT returns.

Originality/value

A key motivation of this paper stems from the mixed findings documented in the literature. Also very little research has been done on the idiosyncratic risk-REIT returns linkage in the Australian context. This study offers unique insights from comparisons: Australia vs the US; and listed vs unlisted REITs.
CSR communication on corporate websites compared across continents
Authors: Hetze Katharina , Winistörfer Herbert
Published: May 2016

Purpose

– The purpose of this paper is to evaluate how the 106 largest banks in the world use their corporate websites for corporate social responsibility (CSR) communication, identifying CSR communication patterns by continent.

Design/methodology/approach

– An analysis of the location of CSR information on the banks’ corporate websites, a longitudinal analysis of the publication of CSR reports by the banks from 2000 to 2012, and a content analysis of the most current CSR reports in the recent period of study were undertaken.

Findings

– Three-quarters of the banks communicate on CSR issues on their corporate website – either located in the section “About Us” or under a separate “CSR” heading which is directly accessible on the front homepage. Company reports published on the website are the most important vehicle for CSR communication. Their publication increased from six for the publication year 2000 to a peak of 63 reports for the year 2011. The reports’ titles are most commonly linked to the concepts of “responsibility” or “sustainability” and refer to ten main stakeholders and topics. In a comparison between continents there is a difference in the use of titles: European banks prefer the title “Sustainability Report”, while Asian and American banks in particular prefer the title “CSR Report”.

Research limitations/implications

– The paper focuses on corporate communications, and therefore does not address perspectives on CSR communication from other disciplines. Within CSR communication, sources of CSR-related information other than the corporate websites have not been considered.

Originality/value

– This paper gives the first comprehensive picture of the trend in CSR communication on corporate websites in the global banking sector.
The role of self-esteem, negative affect and normative influence in impulse buying
Authors: Bandyopadhyay Nirmalya
Published: May 2016

Purpose

– The purpose of this paper is to empirically examine the roles of self-esteem (SE), negative affect (NA), and consumer susceptibility to normative influence in the enactment of impulse buying behavior.

Design/methodology/approach

– A theoretical model is developed through an extensive review of literature. Survey research is conducted to collect the data from respondents. Structural equation modeling is performed to test the model and the hypotheses.

Findings

– The outcome of the study reveals that the act of impulsive buying is preceded by buying impulse (BI). BI is positively influenced by consumer susceptibility to normative influence and impulsive buying tendency (IBT). SE influences the generation of BI partially mediated by IBT.

Research limitations/implications

– The study is limited in its generalizability in terms of its geographic location, culture, and the context of product categories.

Practical implications

– The findings of the study have practical implications in developing marketing communications, merchandising, and personal selling strategies.

Originality/value

– In view of the contradictory empirical evidences in extant literature regarding the role NA the present study re-examines whether NA influences impulse buying. The study, conducted in the field setting also ascertains the external validity of the findings not tested in the prior research. Furthermore, in light of psychology literature, the relationship between SE and IBT was hypothesized and empirically established in the present study.
Does the UK Have Influence in the EU Legislative Process?
Authors: Hix Simon
Published: May 2016

The UK has influenced some major EU policies, such as the creation of the single market and enlargement. But how influential are the UK government and British MEPs in the day‐to‐day EU legislative process? To answer this question, this article analyses recent data from the Council of the European Union and the European Parliament. The evidence is mixed. In the Council, in recent years the UK government has been outvoted more often than any other EU government, yet UK officials remain well connected ‘behind the scenes’. In the European Parliament, British MEPs are now more likely to be on the losing side than are the MEPs of any other member state, yet British MEPs still win key committee chairs and rapporteurships. The evidence suggests that if the UK votes to remain in the EU, Britain's political elites will need to re‐engage with Brussels politics if the UK is to avoid becoming further marginalised from mainstream EU politics.
Industry self‐regulation of alcohol marketing: a systematic review of content and exposure research
Authors: Noel Jonathan K. , Babor Thomas F. , Robaina Katherine
Published: May 2016

Background and Aims

With governments relying increasingly upon the alcohol industry's self‐regulated marketing codes to restrict alcohol marketing activity, there is a need to summarize the findings of research relevant to alcohol marketing controls. This paper provides a systematic review of studies investigating the content of, and exposure to, alcohol marketing in relation to self‐regulated guidelines.

Methods

Peer‐reviewed papers were identified through four literature search engines: SCOPUS, Web of Science, PubMed and PsychINFO. Non‐peer‐reviewed reports produced by public health agencies, alcohol research centers, non‐governmental organizations and government research centers were also identified. Ninety‐six publications met the inclusion criteria.

Results

Of the 19 studies evaluating a specific marketing code and 25 content analysis studies reviewed, all detected content that could be considered potentially harmful to children and adolescents, including themes that appeal strongly to young men. Of the 57 studies of alcohol advertising exposure, high levels of youth exposure and high awareness of alcohol advertising were found for television, radio, print, digital and outdoor advertisements. Youth exposure to alcohol advertising has increased over time, even as greater compliance with exposure thresholds has been documented.

Conclusions

Violations of the content guidelines within self‐regulated alcohol marketing codes are highly prevalent in certain media. Exposure to alcohol marketing, particularly among youth, is also prevalent. Taken together, the findings suggest that the current self‐regulatory systems that govern alcohol marketing practices are not meeting their intended goal of protecting vulnerable populations.
Culture Influences Action Understanding in Infancy: Prediction of Actions Performed With Chopsticks and Spoons in Chinese and Swedish Infants
Authors: Green Dorota , Li Qi , Lockman Jeffrey J. , Gredebäck Gustaf
Published: May 2016

The cultural specificity of action prediction was assessed in 8‐month‐old Chinese and Swedish infants. Infants were presented with an actor eating with a spoon or chopsticks. Predictive goal‐directed gaze shifts were examined using eye tracking. The results demonstrate that Chinese infants only predict the goal of eating actions performed with chopsticks, whereas Swedish infants exclusively predict the goal of eating actions performed with a spoon. Infants in neither culture predicted the goal of object manipulation actions (e.g., picking up food) performed with a spoon or chopsticks. The results support the view that multiple processes (both visual/cultural learning and motor‐based direct matching processes) facilitate goal prediction during observation of other peoples’ actions early in infancy.
CEO Shareholdings and Earnings Manipulation: A Behavioral Explanation
Authors: Petrou Andreas P. , Procopiou Andreas
Published: May 2016

Empirical findings on the relationship between CEO shareholdings and earnings manipulation are inconclusive. In response, this study attempts to shed more light by suggesting that this relationship is influenced by situational contingencies that affect CEO perceptions of the costs and benefits associated with earnings manipulation. To support this perspective we draw on the prospect theory and the approach/inhibition theory of power to examine the relationship between CEO shareholdings and earnings manipulation in light of CEO power. We test this relationship on a sample of 16,873 observations from 2,257 US public firms. Findings show that increasing CEO shareholdings has a negative effect on earnings management, and on re‐statements due to irregularities, and that duality positively moderates these relationships. The findings contribute to the corporate governance practice since they have implications for the design of CEO remuneration packages.
Polarized trafficking of the sorting receptor SorLA in neurons and MDCK cells
Authors: Klinger Stine C. , Højland Anne , Jain Shweta , Kjolby Mads , Madsen Peder , Svendsen Anna Dorst , Olivecrona Gunilla , Bonifacino Juan S. , Nielsen Morten S.
Published: May 2016

The sorting receptor SorLA is highly expressed in neurons and is also found in other polarized cells. The receptor has been reported to participate in the trafficking of several ligands, some of which are linked to human diseases, including the amyloid precursor protein, TrkB, and Lipoprotein Lipase (LpL). Despite this, only the trafficking in nonpolarized cells has been described so far. Due to the many differences between polarized and nonpolarized cells, we examined the localization and trafficking of SorLA in epithelial Madin–Darby canine kidney (MDCK) cells and rat hippocampal neurons. We show that SorLA is mainly found in sorting endosomes and on the basolateral surface of MDCK cells and in the somatodendritic domain of neurons. This polarized distribution of SorLA respectively depends on an acidic cluster and an extended version of this cluster and involves the cellular adaptor complex AP‐1. Furthermore, we show that SorLA can mediate transcytosis across a tight cell layer.