bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish
Authors: Wang Xingang , Zhao Zhonghua , Muller Julius , Iyu Audrey , Khng Alexis Jiaying , Guccione Ernesto , Ruan Yijun , Ingham Philip W. 
Published: September 2013

Summary
Hedgehog (Hh) signaling is mediated by the Gli transcription factors and, in the zebrafish, plays an important role in patterning both the neural tube and myotome. Using a null allele of the gli2a gene induced by targeted mutagenesis, we show that Gli2a is completely dispensable in the fish but acts redundantly with Gli1 to regulate expression of known Hh targets, such as ptch2, prdm1a and eng2a, in the myotome and neural tube. To identify novel targets of Hh signaling, we performed chromatin immunoprecipitation sequencing (ChIP-seq) of whole embryo extracts. Samples were significantly enriched for 192 genomic regions, some of which are associated with four known Hh target genes, ptch1, ptch2, gli1 and olig2. Sequence analysis of these regions reveals a high level of conservation of Gli-binding sites from fish to mammals in some, but not all, cases. Expression analysis of other transcription units that are closely associated with peaks identified several putative targets not previously implicated as Hh targets, including myl10, hnmt, lrp4, efemp2, fras1, quo, and lamc1. Each of these genes shows loss of, or reduced expression in, embryos homozygous for an antimorphic allele of gli2a, you-too (yot), consistent with their being direct targets of Gli2a.
Inflammatory challenge increases measures of oxidative stress in a free-ranging, long-lived mammal
Authors: Schneeberger Karin , Czirják Gábor Á. , Voigt Christian C. 
Published: September 2013

Summary
Oxidative stress - the imbalance between reactive oxygen species (ROS) and neutralising antioxidants - has been under debate as the main cause of ageing in aerobial organisms. The level of ROS should increase during infections as part of the activation of an immune response, leading to oxidative damage on proteins, lipids and DNA. Yet, it is unknown how long-lived organisms, especially mammals, cope with oxidative stress. Bats are known to carry a variety of zoonotic pathogens and at the same time are despite their high mass-specific basal metabolic rate unusually long-lived, which may be partly caused by low oxidative damage of organs. Here, we ask if an immune challenge causes oxidative stress in free-ranging bats, measuring two oxidative stress markers. We injected 20 short-tailed fruit bats (Carollia perspicillata) with bacterial derived lipopolysaccharides (LPS) and 20 individuals with phosphate-buffered saline solution (PBS) as a control. Individuals injected with LPS showed an immune reaction by increased white blood cell count after 24h, whereas there was no significant change in leukocyte counts in control animals. The biological antioxidant potential (BAP) remained the same in both groups, but reactive oxygen metabolites (ROM) increased after treatment with LPS, indicating a significant increase in oxidative stress in animals when mounting an immune reaction toward the inflammatory challenge. Control individuals did not show a change in oxidative stress markers. We conclude that in a long-lived mammal, even high concentrations of antioxidants do not immediately neutralise free radicals produced during a cellular immune response. Thus, fighting an infection may lead to oxidative stress in bats.
Photochromic Performance of 1-Thiazolyl-2-vinylcyclopentene Derivatives Having a Phenyl- or 4-Methoxyphenyl-Substituted Olefin
Authors: Takami Shizuka , Shimizu Ayano , Shimizu Kazuyuki , Miyoshi Ryota , Yamaguchi Tadatsugu , Irie Masahiro 
Published: September 2013

Abstract
1-Thiazolyl-2-vinylcyclopentene derivatives, 1-(5-methoxy-2-phenyl-4-thiazolyl)-2-(2-methyl-1-phenyl-1-propenyl)perfluorocyclopentene (1a), 1-[5-methoxy-2-(4-methoxyphenyl)-4-thiazolyl]-2-(2-methyl-1-phenyl-1-propenyl)perfluorocyclopentene (2a), and 1-[5-methoxy-2-(4-methoxyphenyl)-4-thiazolyl]-2-[1-(4-methoxyphenyl)-2-methyl-1-propenyl]perfluorocyclopentene (3a) were synthesized in an attempt to obtain yellow photochromic compounds having low photocycloreversion quantum yields and large absorption coefficients of the closed-ring isomers. Their photochromic performance, thermal stability, and fatigue resistance were compared with 1-[5-methoxy-2-(4-methoxyphenyl)-4-thiazolyl]-2-(1,2-dimethyl-1-propenyl)perfluorocyclopentene (4a) having a methyl-substituted olefin. Upon irradiation with 313 nm light, compounds 1a, 2a, and 3a changed from colorless to various shades of yellow in toluene. The conversions from the open-ring (1a, 2a, and 3a) to the closed-ring (1b, 2b, and 3b) isomers in the photostationary state under irradiation with 313 nm light were 93, 95, and 98%, respectively. Among the three derivatives 3b has the largest absorption coefficient (ε = 18900 M−1 cm−1) at 428 nm and the lowest cycloreversion quantum yield of 1.8 × 10−3.
Highly diastereoselective synthesis of N-substituted 4-(diethoxyphosphoryl)-pyrrolidines-3-carboxylate starting from tetraethyl methylenediphosphonate
Authors: Ameur Maha , Arfaoui Aicha , Ben Kraiem Jihene , Al-Deyab Salem S. , Amri Hassen 
Published: September 2013

Â This paper describes a convenient synthesis of novel series of 3,4-disubstituted pyrrolidines based on the aza-Michael addition of primary amines to 3,4-difunctionalized-1,3-diene followed by an intramolecular cyclization.
Troponin T and N-Terminal Pro–B-Type Natriuretic Peptide: A Biomarker Approach to Predict Heart Failure Risk—The Atherosclerosis Risk in Communities Study
Authors: Nambi Vijay , Liu Xiaoxi , Chambless Lloyd E , de Lemos James A , Virani Salim S , Agarwal Sunil , Boerwinkle Eric , Hoogeveen Ron C , Aguilar David , Astor Brad C , Srinivas Pothur R , Deswal Anita , Mosley Thomas H , Coresh Josef , Folsom Aaron R , Heiss Gerardo , Ballantyne Christie M 
Published: September 2013

BACKGROUND
Among the various cardiovascular diseases, heart failure (HF) is projected to have the largest increases in incidence over the coming decades; therefore, improving HF prediction is of significant value. We evaluated whether cardiac troponin T (cTnT) measured with a high-sensitivity assay and N-terminal pro–B-type natriuretic peptide (NT-proBNP), biomarkers strongly associated with incident HF, improve HF risk prediction in the Atherosclerosis Risk in Communities (ARIC) study.

METHODS
Using sex-specific models, we added cTnT and NT-proBNP to age and race (“laboratory report” model) and to the ARIC HF model (includes age, race, systolic blood pressure, antihypertensive medication use, current/former smoking, diabetes, body mass index, prevalent coronary heart disease, and heart rate) in 9868 participants without prevalent HF; area under the receiver operating characteristic curve (AUC), integrated discrimination improvement, net reclassification improvement (NRI), and model fit were described.

RESULTS
Over a mean follow-up of 10.4 years, 970 participants developed incident HF. Adding cTnT and NT-proBNP to the ARIC HF model significantly improved all statistical parameters (AUCs increased by 0.040 and 0.057; the continuous NRIs were 50.7% and 54.7% in women and men, respectively). Interestingly, the simpler laboratory report model was statistically no different than the ARIC HF model.

CONCLUSIONS
cTnT and NT-proBNP have significant value in HF risk prediction. A simple sex-specific model that includes age, race, cTnT, and NT-proBNP (which can be incorporated in a laboratory report) provides a good model, whereas adding cTnT and NT-proBNP to clinical characteristics results in an excellent HF prediction model.
The Value of Diagnostic Testing in Personalized Medicine
Authors: Goldman Dana P. , Gupta Charu , Vasudeva Eshan , Trakas Kostas , Riley Ralph , Lakdawalla Darius , Agus David , Sood Neeraj , Jena Anupam B. , Philipson Tomas J. 
Published: September 2013

Abstract
Personalized medicine – the targeting of therapies to individuals on the basis of their biological, clinical, or genetic characteristics – is thought to have the potential to transform health care. While much emphasis has been placed on the value of personalized therapies, less attention has been paid to the value generated by the diagnostic tests that direct patients to those targeted treatments. This paper presents a framework derived from information economics for assessing the value of diagnostics. We demonstrate, via a case study, that the social value of such diagnostics can be very large, both by avoiding unnecessary treatment and by identifying patients who otherwise would not get treated. Despite the potential social benefits, diagnostic development has been discouraged by cost-based, rather than value-based, reimbursement.
Kinetochore Function and Chromosome Segregation Rely on Critical Residues in Histones H3 and H4 in Budding Yeast
Authors: Ng Tessie M , Lenstra Tineke L , Duggan Nicole , Jiang Shuangying , Ceto Steven , Holstege Frank C P , Dai Junbiao , Boeke Jef D , Biggins Sue 
Published: September 2013

Abstract
Accurate chromosome segregation requires that sister kinetochores biorient and attach to microtubules from opposite poles. Kinetochore biorientation relies on the underlying centromeric chromatin, which provides a platform to assemble the kinetochore and to recruit the regulatory factors that ensure the high fidelity of this process. To identify the centromeric chromatin determinants that contribute to chromosome segregation, we performed two complementary unbiased genetic screens using a library of budding yeast mutants in every residue of histone H3 and H4. In one screen, we identified mutants that lead to increased loss of a nonessential chromosome. In the second screen, we isolated mutants whose viability depends on a key regulator of biorientation, the Aurora B protein kinase. Nine mutants were common to both screens and exhibited kinetochore biorientation defects. Four of the mutants map near the unstructured nucleosome entry site, and their genetic interaction with reduced IPL1 can be suppressed by increasing the dosage of SGO1, a key regulator of biorientation. In addition, the composition of purified kinetochores was altered in six of the mutants. Together, this work identifies previously unknown histone residues involved in chromosome segregation and lays the foundation for future studies on the role of the underlying chromatin structure in chromosome segregation.
Relating Phylogenetic Trees to Transmission Trees of Infectious Disease Outbreaks
Authors: Ypma Rolf J F , van Ballegooijen W Marijn , Wallinga Jacco 
Published: September 2013

Abstract
Transmission events are the fundamental building blocks of the dynamics of any infectious disease. Much about the epidemiology of a disease can be learned when these individual transmission events are known or can be estimated. Such estimations are difficult and generally feasible only when detailed epidemiological data are available. The genealogy estimated from genetic sequences of sampled pathogens is another rich source of information on transmission history. Optimal inference of transmission events calls for the combination of genetic data and epidemiological data into one joint analysis. A key difficulty is that the transmission tree, which describes the transmission events between infected hosts, differs from the phylogenetic tree, which describes the ancestral relationships between pathogens sampled from these hosts. The trees differ both in timing of the internal nodes and in topology. These differences become more pronounced when a higher fraction of infected hosts is sampled. We show how the phylogenetic tree of sampled pathogens is related to the transmission tree of an outbreak of an infectious disease, by the within-host dynamics of pathogens. We provide a statistical framework to infer key epidemiological and mutational parameters by simultaneously estimating the phylogenetic tree and the transmission tree. We test the approach using simulations and illustrate its use on an outbreak of foot-and-mouth disease. The approach unifies existing methods in the emerging field of phylodynamics with transmission tree reconstruction methods that are used in infectious disease epidemiology.
Neurodegeneration Caused by Polyglutamine Expansion Is Regulated by P-Glycoprotein in Drosophila melanogaster
Authors: Yadav Suman , Tapadia Madhu G 
Published: September 2013

Abstract
Trinucleotide CAG repeat disorders are caused by expansion of polyglutamine (polyQ) domains in certain proteins leading to fatal neurodegenerative disorders and are characterized by accumulation of inclusion bodies in the neurons. Clearance of these inclusion bodies holds the key to improve the disease phenotypes, which affects basic cellular processes such as transcription, protein degradation and cell signaling. In the present study, we show that P-glycoprotein (P-gp), originally identified as a causative agent of multidrug-resistant cancer cells, plays an important role in ameliorating the disease phenotype. Using a Drosophila transgenic strain that expresses a stretch of 127 glutamine repeats, we demonstrate that enhancing P-gp levels reduces eye degeneration caused by expression of polyQ, whereas reducing it increases the severity of the disease. Increase in polyQ inclusion bodies represses the expression of mdr genes, suggesting a functional link between P-gp and polyQ. P-gp up-regulation restores the defects in the actin organization and precise array of the neuronal connections caused by inclusion bodies. β-Catenin homolog, Armadillo, also interacts with P-gp and regulates the accumulation of inclusion bodies. These results thus show that P-gp and polyQ interact with each other, and changing P-gp levels can directly affect neurodegeneration.
High-Resolution Mapping of Complex Traits with a Four-Parent Advanced Intercross Yeast Population
Authors: Cubillos Francisco A , Parts Leopold , Salinas Francisco , Bergström Anders , Scovacricchi Eugenio , Zia Amin , Illingworth Christopher J R , Mustonen Ville , Ibstedt Sebastian , Warringer Jonas , Louis Edward J , Durbin Richard , Liti Gianni 
Published: September 2013

AbstractA large fraction of human complex trait heritability is due to a high number of variants with small marginal effects and their interactions with genotype and environment. Such alleles are more easily studied in model organisms, where environment, genetic makeup, and allele frequencies can be controlled. Here, we examine the effect of natural genetic variation on heritable traits in a very large pool of baker’s yeast from a multiparent 12th generation intercross. We selected four representative founder strains to produce the Saccharomyces Genome Resequencing Project (SGRP)-4X mapping population and sequenced 192 segregants to generate an accurate genetic map. Using these individuals, we mapped 25 loci linked to growth traits under heat stress, arsenite, and paraquat, the majority of which were best explained by a diverging phenotype caused by a single allele in one condition. By sequencing pooled DNA from millions of segregants grown under heat stress, we further identified 34 and 39 regions selected in haploid and diploid pools, respectively, with most of the selection against a single allele. While the most parsimonious model for the majority of loci mapped using either approach was the effect of an allele private to one founder, we could validate examples of pleiotropic effects and complex allelic series at a locus. SGRP-4X is a deeply characterized resource that provides a framework for powerful and high-resolution genetic analysis of yeast phenotypes and serves as a test bed for testing avenues to attack human complex traits.
Genomic Resources for Gene Discovery, Functional Genome Annotation, and Evolutionary Studies of Maize and Its Close Relatives
Authors: Wang Chao , Shi Xue , Liu Lin , Li Haiyan , Ammiraju Jetty S S , Kudrna David A , Xiong Wentao , Wang Hao , Dai Zhaozhao , Zheng Yonglian , Lai Jinsheng , Jin Weiwei , Messing Joachim , Bennetzen Jeffrey L , Wing Rod A , Luo Meizhong 
Published: September 2013

Abstract
Maize is one of the most important food crops and a key model for genetics and developmental biology. A genetically anchored and high-quality draft genome sequence of maize inbred B73 has been obtained to serve as a reference sequence. To facilitate evolutionary studies in maize and its close relatives, much like the Oryza Map Alignment Project (OMAP) (www.OMAP.org) bacterial artificial chromosome (BAC) resource did for the rice community, we constructed BAC libraries for maize inbred lines Zheng58, Chang7-2, and Mo17 and maize wild relatives Zea mays ssp. parviglumis and Tripsacum dactyloides. Furthermore, to extend functional genomic studies to maize and sorghum, we also constructed binary BAC (BIBAC) libraries for the maize inbred B73 and the sorghum landrace Nengsi-1. The BAC/BIBAC vectors facilitate transfer of large intact DNA inserts from BAC clones to the BIBAC vector and functional complementation of large DNA fragments. These seven Zea Map Alignment Project (ZMAP) BAC/BIBAC libraries have average insert sizes ranging from 92 to 148 kb, organellar DNA from 0.17 to 2.3%, empty vector rates between 0.35 and 5.56%, and genome equivalents of 4.7- to 8.4-fold. The usefulness of the Parviglumis and Tripsacum BAC libraries was demonstrated by mapping clones to the reference genome. Novel genes and alleles present in these ZMAP libraries can now be used for functional complementation studies and positional or homology-based cloning of genes for translational genomics.
Current Understanding and Management of Medullary Thyroid Cancer
Authors: Roy Madhuchhanda , Chen Herbert , Sippel Rebecca S. 
Published: September 2013

Learning Objectives
Identify and evaluate a patient with a diagnosis of medullary thyroid cancer. Utilize genetic testing for the RET proto-oncogene and explain how the location of the mutation affects the risks for the patient. Select among the surgical treatment options for patients with medullary thyroid cancer, including prophylactic surgery in genetic carriers.
Alopecia With Endocrine Therapies in Patients With Cancer
Authors: Saggar Vishal , Wu Shenhong , Dickler Maura N. , Lacouture Mario E. 
Published: September 2013

Learning Objectives
Define the incidence and grades of alopecia to endocrine-based therapies in cancer patients. Differentiate risk of alopecia to various endocrine agents used against cancer. Design therapeutic, counseling, and supportive care strategies for patients requiring endocrine agents causing alopecia.
Relationship between Cognitive Function, Depression/Anxiety and Functional Parameters in Patients Admitted for Congestive Heart Failure
Authors: Feola Mauro , Garnero Sonia , Vallauri Paola , Salvatico Luigi , Vado Antonello , Leto Laura , Testa Marzia 
Published: September 2013

Cognitive impairment, anxiety and depression have been described in patients with congestive heart failure (CHF). We analyzed in-hospital CHF patients before discharge with neuropsychological tests attempting to correlate with prognostic parameters.

Methods:
All subjects underwent a mini mental state examination (MMSE), geriatric depression scale (GDS), anxiety and depression scale test (HADS). We evaluated NYHA class, brain natriuretic peptide (BNP), left ventricular ejection fraction (LVEF) and non-invasive cardiac output (CO).

Results:
Three-hundred and three CHF patients (age 71.6 ys) were analysed. The mean NYHA class was 2.9±0.8, LVEF was 43.4±15.8%; BNP plasma level and CO were calculated as 579.8±688.4 pg/ml and 3.9±1.1 l/min, respectively. In 9.6% a pathological MMSE score emerged; a depression of mood in 18.2% and anxiety in 23.4% of patients were observed. A significant correlation between MMSE and age (r=0.11 p=0.001), BNP (r=0.64 p=0.03) but not between MMSE and NYHA class and LVEF was observed. GDS and HADS were inversely correlated with NYHA class (r=0.38 p=0.04) and six-minute walking test (r=0.18 p=0.01) without an association with objective parameters in CHF (BNP, LVEF and cardiac output). At multivariate analysis only MMSE and BNP are inversely correlated significantly (p=0.019 OR=-0.64, CI=-042-0.86).

Conclusions:
in-hospital CHF patients may manifest a reduction of MMSE and important anxiety/depression disorders. The results of the study suggest that the presence of cognitive impairment in older CHF patients with higher BNP plasma level should be considered. In admitted CHF patients anxiety and depression of mood are commonly reported and influenced the perception of the severity of illness.
Hybrid photonics structures with grating and prism couplers based on ZnO waveguides
Authors: Struk P. , Pustelny T. , Gołaszewska K. , Kamińska E. , Borysiewicz M. , Ekielski M. , Piotrowska A. 
Published: September 2013

AbstractThis paper presents the results of investigations concerning input-output systems of an electromagnetic wave in the visible and near visible spectrum for their application in structures of integrated optics. The input-output structures used in described planar optical waveguides are in a form of prism and grating couplers. The first part of the paper contains numerical analysis of grating couplers aiming at an optimization of their geometrical parameters, strictly — the depth of the grooves in the grating coupler. The second part presents the practical realization, as well as experimental tests of the planar optical waveguide with the hybrid input-output system. As the input system of the electromagnetic wave, a prism coupler was used, and in the case of the output system — a photonic structure with grating coupler was applied. The investigated planar wave guides with the input-output structures were made of a wide energy band gap semiconductor — zinc oxide (ZnO).
Real time area-based stereo matching algorithm for multimedia video devices
Authors: Hachaj T. , Ogiela M. 
Published: September 2013

AbstractIn this paper we investigate stereovision algorithms that are suitable for multimedia video devices. The main novel contribution of this article is detailed analysis of modern graphical processing unit (GPU)-based dense local stereovision matching algorithm for real time multimedia applications. We considered two GPU-based implementations and one CPU implementation (as the baseline). The results (in terms of frame per second, fps) were measured twenty times per algorithm configuration and, then averaged (the standard deviation was below 5%). The disparity range was [0,20], [0,40], [0,60], [0,80], [0,100] and [0,120]. We also have used three different matching window sizes (3×3, 5×5 and 7×7) and three stereo pair image resolutions 320×240, 640×480 and 1024×768. We developed our algorithm under assumption that it should process data with the same speed as it arrives from captures’ devices. Because most popular of the shelf video cameras (multimedia video devices) capture data with the frequency of 30Hz, this frequency was threshold to consider implementation of our algorithm to be “real time”. We have proved that our GPU algorithm that uses only global memory can be used successfully in that kind of tasks. It is very important because that kind of implementation is more hardware-independent than algorithms that operate on shared memory. Knowing that we might avoid the algorithms failure while moving the multimedia application between machines operating different hardware. From our knowledge this type of research has not been yet reported.