bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rural‐Urban Differences in Chronic Disease and Drug Utilization in Older Oregonians
Authors: Goeres Leah M. , Gille Allison , Furuno Jon P. , Erten‐Lyons Deniz , Hartung Daniel M. , Calvert James F. , Ahmed Sharia M. , Lee David S.H. 
Published: October 2015

AbstractPurposeTo characterize disease burden and medication usage in rural and urban adults aged ≥85 years.MethodsThis is a secondary analysis of 5 years of longitudinal data starting in the year 2000 from 3 brain‐aging studies. Cohorts consisted of community‐dwelling adults: 1 rural cohort, the Klamath Exceptional Aging Project (KEAP), was compared to 2 urban cohorts, the Oregon Brain Aging Study (OBAS) and the Dementia Prevention study (DPS). In this analysis, 121 participants were included from OBAS/DPS and 175 participants were included from KEAP. Eligibility was determined based on age ≥85 years and having at least 2 follow‐up visits after the year 2000. Disease burden was measured by the Modified Cumulative Illness Rating Scale (MCIRS), with higher values representing more disease. Medication usage was measured by the estimated mean number of medications used by each cohort.FindingsRural participants had significantly higher disease burden as measured by MCIRS, 23.0 (95% CI: 22.3‐23.6), than urban participants, 21.0 (95% CI: 20.2‐21.7), at baseline. The rate of disease accumulation was a 0.2 increase in MCIRS per year (95% CI: 0.05‐0.34) in the rural population. Rural participants used a higher mean number of medications, 5.5 (95% CI: 4.8‐6.1), than urban participants, 3.7 (95% CI: 3.1‐4.2), at baseline (P < .0001).ConclusionsThese data suggest that rural and urban Oregonians aged ≥85 years may differ by disease burden and medication usage. Future research should identify opportunities to improve health care for older adults.
Misallocation and Total Factor Productivity in Italy: Evidence from Firm‐Level Data
Authors: Calligaris Sara 
Published: November 2015

AbstractOver the last two decades, total factor productivity (TFP) in Italy decreased by 0.2% per year, while increasing on average in the Euro‐area countries. This decline suggests the existence of large inefficiencies in the allocation of resources, making the Italian case particularly interesting and suitable in order to study the role of misallocation. In this article, I quantify the within‐industry misallocation of inputs in Italy over the period 1993–2011, by applying the Hsieh and Klenow's methodology. Using a micro‐level longitudinal dataset of Italian manufacturing firms, I find that, in the hypothetical absence of distortions, aggregate TFP in manufacturing would be boosted by 58% in 1993, by 67% in 2006 and by 80% in 2011. This leads to a twofold conclusion: first, misallocation plays a crucial role in determining the inefficiency level of the Italian manufacturing sector; second, misallocation has increased over time. Given the magnitude of the results obtained and the policy implications related thereto, I take a step ahead by checking to what extent the degree of misallocation can be attributed to specific characteristics of the Italian firms: it emerges that misallocation is higher for firms located in the south and at low‐technological intensity, as well as for small or young firms.
Authorization and the Right to Punish in Hobbes
Authors: Green Michael J. 
Published: October 2015

AbstractThis article answers questions about the consistency, coherence, and motivation of Hobbes's account of the right to punish. First, it develops a novel account of authorization that explains how Hobbes could have consistently held both that the subjects do not give the sovereign the right to punish and also that they authorize the sovereign to punish. Second, it shows that, despite appearances, the natural and artificial elements of Hobbes's account form a coherent whole. Finally, it explains why Hobbes thought it was important to establish the sovereign's right to punish apart from the sovereign's power to punish.
Variation in circadian rhythms is maintained among and within populations in Boechera stricta
Authors: Salmela Matti J. , Greenham Kathleen , Lou Ping , McClung C. Robertson , Ewers Brent E. , Weinig Cynthia 
Published: October 2015

AbstractCircadian clocks have evolved independently in all three domains of life, and fitness benefits of a functional clock have been demonstrated in experimental genotypes in controlled conditions. Still, little is known about genetic variation in the clock and its fitness consequences in natural populations from heterogeneous environments. Using Wyoming populations of the Arabidopsis relative Boechera stricta as our study system, we demonstrate that genetic variation in the clock can occur at multiple levels: means of circadian period among populations sampled at different elevations differed by less than 1 h, but means among families sampled within populations varied by as much as 3.5 h. Growth traits also varied among and within populations. Within the population with the most circadian variation, we observed evidence for a positive correlation between period and growth and a negative correlation between period and root‐to‐shoot ratio. We then tested whether performance tradeoffs existed among families of this population across simulated seasonal settings. Growth rankings of families were similar across seasonal environments, but for root‐to‐shoot ratio, genotype × environment interactions contributed significantly to total variation. Therefore, further experiments are needed to identify evolutionary mechanisms that preserve substantial quantitative genetic diversity in the clock in this and other species.
Insights into genetic alterations of liver metastases from uveal melanoma
Authors: McCarthy Conni , Kalirai Helen , Lake Sarah L. , Dodson Andrew , Damato Bertil E. , Coupland Sarah E. 
Published: November 2015

SummaryThe liver is the organ usually affected by metastatic uveal melanoma (MUM). Current treatments are almost always ineffective and mortality remains high. In this study, copy number variations (CNVs) were identified in 12 metastatic and five matched primary UMs (PUMs). Our data revealed a wide spectrum of genetic alterations in MUM. Most common were amplifications of chromosome (chr.) 8q; alterations on chr. 3 included monosomy, isodisomy, and large regions of homozygosity (ROH). Genomic profiles of PUM‐MUM pairs varied in their degree of similarity and complexity. However, within the pairs, 135 genes were consistently altered. Protein expression of C‐MYC and BAP1 was examined by immunohistochemistry (IHC); a positive association between IHC and CNVs was seen for C‐MYC. This comprehensive catalogue of CNVs associated with MUM should facilitate the identification of key alterations that drive tumor growth. This would have the potential to select urgently needed novel, targeted, therapeutic regimens.
Characterization of bovine MHC class II DRB3 diversity in South American Holstein cattle populations
Authors: Takeshima S.‐N. , Giovambattista G. , Okimoto N. , Matsumoto Y. , Rogberg‐Muñoz A. , Acosta T. J. , Onuma M. , Aida Y. 
Published: October 2015

AbstractHolstein cattle dominate the global milk production industry because of their outstanding milk production, however, this breed is susceptible to tropical endemic pathogens and suffers from heat stress and thus fewer Holstein populations are raised in tropical areas. The bovine major histocompatibility complex (BoLA)‐DRB3 class II gene is used as a marker for disease and immunological traits, and its polymorphism has been studied extensively in Holstein cattle from temperate and cold regions. We studied the genetic diversity of the BoLA‐DRB3 gene in South American Holstein populations to determine whether tropical populations have diverged from those bred in temperate and cold regions by selection and/or crossbreeding with local native breeds. We specifically studied Exon 2 of this gene from 855 South American Holstein individuals by a polymerase chain reaction (PCR) sequence‐based typing method. We found a high degree of gene diversity at the allelic (Na > 20 and He > 0.87) and molecular (π > 0.080) levels, but a low degree of population structure (FST = 0.009215). A principal components analysis and tree showed that the Bolivian subtropical population had the largest genetic divergence compared with Holsteins bred in temperate or cold regions, and that this population was closely related to Bolivian Creole cattle. Our results suggest that Holstein genetic divergence can be explained by selection and/or gene introgression from local germplasms. This is the first examination of BoLA‐DRB3 in Holsteins adapted to tropical environments, and contributes to an ongoing effort to catalog bovine MHC allele frequencies by breed and location.
Assessing Export Competitiveness through the Lens of Value Added
Authors: Ceglowski Janet 
Published: October 2015

AbstractExtensive changes in the organization of world trade over the last two decades have renewed concerns about countries’ ability to compete in export markets. The impact could be especially large in industries that participate in global value chains (GVCs). This study assesses the recent export performance of 56 countries in five industries associated with GVCs using an index of normalised revealed comparative advantage (RCA) that can be compared across industries and countries and new data on the domestic value added in exports from the OECD's Trade in Value‐added database. For a number of the GVC industries, countries identified as the most competitive based on gross exports are often found to be less competitive when evaluated in terms of domestic value added. Business services are an important exception; several countries appear more competitive on a value‐added basis than based on conventional measures of gross exports. Despite concerns about hollowing out, a number of major industrial countries remain highly competitive in one or more GVC industries, even from the perspective of domestic value added. A value‐added approach to RCA provides insights that are not apparent from an exclusive focus on gross exports.
Evaluation of the local dose enhancement in the combination of proton therapy and nanoparticles
Authors: Martínez‐Rovira I. , Prezado Y. 
Published: October 2015

Purpose:The outcome of radiotherapy can be further improved by combining irradiation with dose enhancers such as high‐Z nanoparticles. Since 2004, spectacular results have been obtained when low‐energy x‐ray irradiations have been combined with nanoparticles. Recently, the same combination has been explored in hadron therapy. In vitro studies have shown a significant amplification of the biological damage in tumor cells charged with nanoparticles and irradiated with fast ions. This has been attributed to the increase in the ionizations and electron emissions induced by the incident ions or the electrons in the secondary tracks on the high‐Z atoms, resulting in a local energy deposition enhancement. However, this subject is still a matter of controversy. Within this context, the main goal of the authors’ work was to provide new insights into the dose enhancement effects of nanoparticles in proton therapy.Methods:For this purpose, Monte Carlo calculations (gate/geant4 code) were performed. In particular, the geant4‐DNA toolkit, which allows the modeling of early biological damages induced by ionizing radiation at the DNA scale, was used. The nanometric radial energy distributions around the nanoparticle were studied, and the processes (such as Auger deexcitation or dissociative electron attachment) participating in the dose deposition of proton therapy treatments in the presence of nanoparticles were evaluated. It has been reported that the architecture of Monte Carlo calculations plays a crucial role in the assessment of nanoparticle dose enhancement and that it may introduce a bias in the results or amplify the possible final dose enhancement. Thus, a dosimetric study of different cases was performed, considering Au and Gd nanoparticles, several nanoparticle sizes (from 4 to 50 nm), and several beam configurations (source‐nanoparticle distances and source sizes).Results:This Monte Carlo study shows the influence of the simulations’ parameters on the local dose enhancement and how more realistic configurations lead to a negligible increase of local energy deposition. The obtained dose enhancement factor was up to 1.7 when the source was located at the nanoparticle surface. This dose enhancement was reduced when the source was located at further distances (i.e., in more realistic situations). Additionally, no significant increase in the dissociative electron attachment processes was observed.Conclusions:The authors’ results indicate that physical effects play a minor role in the amplification of damage, as a very low dose enhancement or increase of dissociative electron attachment processes is observed when the authors get closer to more realistic simulations. Thus, other effects, such as biological or chemical processes, may be mainly responsible for the enhanced radiosensibilization observed in biological studies. However, more biological studies are needed to verify this hypothesis.
Complete Genome Sequences of Grapevine Yellow Speckle Viroid 1 and Hop Stunt Viroid Assembled from the Transcriptome of
Ixeridium dentatum
Plants
Authors: Lee Joong-Hwan , Lim Seungmo , Lee Seung-Won , Yoo Ran Hee , Igori Davaajargal , Zhao Fumei , Yoon Youngnam , Lee Su-Heon , Moon Jae Sun 
Published: October 2015

ABSTRACT

Here, we report complete genome sequences of grapevine yellow speckle viroid 1 (GYSVd1) and hop stunt viroid (HSVd), members of the family
Pospiviroidae
, assembled from the transcriptome data generated from
Ixeridium dentatum
plants. To our knowledge, this is the first report of GYSVd1 and HSVd in
I. dentatum
.
Draft Genome Sequence and Assembly of Photorhabdus heterorhabditis Strain VMG, a Bacterial Symbiont Associated with the Entomopathogenic Nematode
Heterorhabditis zealandica
Authors: Naidoo Stephanie , Mothupi Boipelo , Featherston Jonathan , Mpangase Phelelani T. , Gray Vincent M. 
Published: October 2015

ABSTRACT

Here, we report the draft genome sequence of
Photorhabdus heterorhabditis
strain VMG, a symbiont of the entomopathogenic nematode
Heterorhabditis zealandica
in South Africa. The draft genome sequence is 4,878,919 bp long and contains 4,023 protein-coding genes. The genome assembly contains 262 contigs with a G+C content of 42.22%.
Complete Genome Sequence of Herbaspirillum hiltneri N3 (DSM 17495), Isolated from Surface-Sterilized Wheat Roots
Authors: Guizelini Dieval , Saizaki Paula M. , Coimbra Nilson A. R. , Weiss Vinicius A. , Faoro Helisson , Sfeir Michelle Z. T. , Baura Valter A. , Monteiro Rose A. , Chubatsu Leda S. , Souza Emanuel M. , Cruz Leonardo M. , Pedrosa Fabio O. , Raittz Roberto T. , Marchaukoski Jeroniza N. , Steffens Maria B. R. 
Published: October 2015

ABSTRACT

We report the complete genome sequence of
Herbaspirillum hiltneri
N3 (DSM 17495), a member of the genus
Herbaspirillum
of the
Betaproteobacteria
. The genome is contained in a single chromosome, and analysis revealed that N3 lacks the whole nitrogen fixation (
nif
) gene cluster, confirming its inability to fix nitrogen.
InSAR monitoring using RADARSAT-2 data at Piton de la Fournaise (La Reunion) and Karthala (Grande Comore) volcanoes
Authors: Catry Thibault , Villeneuve Nicolas , Froger Jean-Luc , Maggio Giuseppe 
Published: October 2015

Abstract
Piton de la Fournaise (La Reunion) and Karthala (Grande Comore) are the two active volcanoes of the Southwestern Indian Ocean. A 14 month (April 2013 to June 2014) monitoring period was carried out at both volcanoes using synthetic aperture RADAR interferometry (InSAR) techniques on RADARSAT-2 data. Thanks to the SEAS-OI (Survey of Environment Assisted by Satellite in the Indian Ocean) station, 21 SAR scenes were acquired over this period and InSAR results revealed the slow subsidence of the Dolomieu caldera floor at Piton de la Fournaise, following the 2009 and 2010 eruptions, and the subsidence of the whole cone between April and July 2013. At Karthala no evidence of any volcanic activity was found for the period April 2013 to June 2014. The use of systematic InSAR for volcano monitoring is an efficient tool to study effusive eruptions. We showed that, during periods of unrest, InSAR is able to pick up early signs of a future eruption and monitor secondary phenomena that require no real-time data. During an effusive crisis, it is still difficult to carry out fully operational InSAR monitoring, but using the example of the June 2014 eruption at Piton de la Fournaise, we show that SAR data can help with the detection and tracking of lava flows and active flow paths during effusive eruptions, based on SAR coherence and SAR amplitude. These preliminary results are very promising for the future of InSAR monitoring of active volcanoes and highlight the need for near-real-time access to SAR data in the mapping of active lava flows during effusive eruptions. This study also revealed the major role of ground stations like SEAS-OI in the efficiency of this monitoring, supplying free, near-real-time remote sensing data to the scientific and institutional communities.
Cancer Neoantigens and Applications for Immunotherapy
Authors: Desrichard Alexis , Snyder Alexandra , Chan Timothy A. 
Published: October 2015

Abstract
Recent advances in immune checkpoint blockade therapy have revolutionized the treatment of cancer. Tumor-specific antigens that are generated by somatic mutation, neoantigens, can influence patient response to immunotherapy and contribute to tumor shrinkage. Recent evidence demonstrating the success of checkpoint blockade immunotherapy in boosting T-cell reactivity against patient-specific neoantigens constitutes a strong rationale for the development of personalized vaccines against these nonself peptides. With the decreasing cost of next-generation sequencing, peptide manufacturing, and improvement of in silico prediction of peptide immunogenicity, it is increasingly important to evaluate the potential use of neoantigens in both diagnosis and treatment. Specifically, these neoantigens could be useful both as predictors of immune checkpoint blockade therapy response and/or incorporated in therapeutic vaccination strategies. Clin Cancer Res; 22(4); 807–12. ©2015 AACR.
Dual Metronomic Chemotherapy with Nab-Paclitaxel and Topotecan Has Potent Antiangiogenic Activity in Ovarian Cancer
Authors: Previs Rebecca A. , Armaiz-Pena Guillermo N. , Lin Yvonne G. , Davis Ashley N. , Pradeep Sunila , Dalton Heather J. , Hansen Jean M. , Merritt William M. , Nick Alpa M. , Langley Robert R. , Coleman Robert L. , Sood Anil K. 
Published: October 2015

Abstract
There is growing recognition of the important role of metronomic chemotherapy in cancer treatment. On the basis of their unique antiangiogenic effects, we tested the efficacy of nab-paclitaxel, which stimulates thrombospondin-1, and topotecan, which inhibits hypoxia-inducible factor 1-α, at metronomic dosing for the treatment of ovarian carcinoma. In vitro and in vivo SKOV3ip1, HeyA8, and HeyA8-MDR (taxane-resistant) orthotopic models were used to examine the effects of metronomic nab-paclitaxel and metronomic topotecan. We examined cell proliferation (Ki-67), apoptosis (cleaved caspase-3), and angiogenesis (microvessel density, MVD) in tumors obtained at necropsy. In vivo therapy experiments demonstrated treatment with metronomic nab-paclitaxel alone and in combination with metronomic topotecan resulted in significant reductions in tumor weight (62% in the SKOV3ip1 model, P &lt; 0.01 and 96% in the HeyA8 model, P &lt; 0.03) compared with vehicle (P &lt; 0.01). In the HeyA8-MDR model, metronomic monotherapy with either cytotoxic agent had modest effects on tumor growth, but combination therapy decreased tumor burden by 61% compared with vehicle (P &lt; 0.03). The greatest reduction in MVD (P &lt; 0.05) and proliferation was seen in combination metronomic therapy groups. Combination metronomic therapy resulted in prolonged overall survival in vivo compared with other groups (P &lt; 0.001). Tube formation was significantly inhibited in RF-24 endothelial cells exposed to media conditioned with metronomic nab-paclitaxel alone and media conditioned with combination metronomic nab-paclitaxel and metronomic topotecan. The combination of metronomic nab-paclitaxel and metronomic topotecan offers a novel, highly effective therapeutic approach for ovarian carcinoma that merits further clinical development. Mol Cancer Ther; 14(12); 2677–86. ©2015 AACR.
Silibinin Preferentially Radiosensitizes Prostate Cancer by Inhibiting DNA Repair Signaling
Authors: Nambiar Dhanya K. , Rajamani Paulraj , Deep Gagan , Jain Anil K. , Agarwal Rajesh , Singh Rana P. 
Published: October 2015

Abstract
Radiotherapy, a frequent mode of cancer treatment, is often restricted by dose-related toxicity and development of therapeutic resistance. To develop a novel and selective radiosensitizer, we studied the radiosensitizing effects and associated mechanisms of silibinin in prostate cancer. The radiosensitizing effect of silibinin with ionizing radiation (IR) was assessed on radioresistant prostate cancer cell lines by clonogenic, cell cycle, cell death, and DNA repair assays. Tumor xenograft growth, immunohistochemical (IHC) analysis of tumor tissues, and toxicity-related parameters were measured in vivo. Silibinin (25 μmol/L) enhanced IR (2.5–10 Gy)-caused inhibition (up to 96%, P &lt; 0.001) of colony formation selectively in prostate cancer cells, and prolonged and enhanced IR-caused G2–M arrest, apoptosis, and ROS production. Mechanistically, silibinin inhibited IR-induced DNA repair (ATM and Chk1/2) and EGFR signaling and attenuated the levels of antiapoptotic proteins. Specifically, silibinin suppressed IR-induced nuclear translocation of EGFR and DNA-PK, an important mediator of DSB repair, leading to an increased number of γ-H2AX (ser139) foci suggesting lesser DNA repair. In vivo, silibinin strongly radiosensitized DU145 tumor xenograft inhibition (84%, P &lt; 0.01) with higher apoptotic response (10-fold, P &lt; 0.01) and reduced repair of DNA damage, and rescued the mice from IR-induced toxicity and hematopoietic injury. Overall, silibinin enhanced the radiotherapeutic response via suppressing IR-induced prosurvival signaling and DSB repair by inhibiting nuclear translocation of EGFR and DNA-PK. Because silibinin is already in phase II clinical trial for prostate cancer patients, the present finding has translational relevance for radioresistant prostate cancer. Mol Cancer Ther; 14(12); 2722–34. ©2015 AACR.