bluuebunny/crossref_metadata_2025_split huggingface dataset:
17q25 Locus Is Associated With White Matter Hyperintensity Volume in Ischemic Stroke, But Not With Lacunar Stroke Status
Authors: Adib-Samii Poneh , Rost Natalia , Traylor Matthew , Devan William , Biffi Alessandro , Lanfranconi Silvia , Fitzpatrick Kaitlin , Bevan Steve , Kanakis Allison , Valant Valerie , Gschwendtner Andreas , Malik Rainer , Richie Alexa , Gamble Dale , Segal Helen , Parati Eugenio A. , Ciusani Emilio , Holliday Elizabeth G. , Maguire Jane , Wardlaw Joanna , Worrall Bradford , Bis Joshua , Wiggins Kerri L. , Longstreth Will , Kittner Steve J. , Cheng Yu-Ching , Mosley Thomas , Falcone Guido J. , Furie Karen L. , Leiva-Salinas Carlos , Lau Benison C. , Saleem Khan Muhammed ,   Australian Stroke Genetics Collaborative,   Wellcome Trust Case-Control Consortium-2 (WTCCC2),   METASTROKE, Sharma Pankaj , Fornage Myriam , Mitchell Braxton D. , Psaty Bruce M. , Sudlow Cathie , Levi Christopher , Boncoraglio Giorgio B. , Rothwell Peter M. , Meschia James , Dichgans Martin , Rosand Jonathan , Markus Hugh S. 
Published: May 2013

Background and Purpose—
Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke.

Methods—
We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke.

Results—

Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (
P
=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke.

Conclusions—
This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction.
Estimation of Random-Coefficient Demand Models: Two Empiricists' Perspective
Authors: Knittel Christopher R. , Metaxoglou Konstantinos 
Published: May 2013

AbstractWe document the numerical challenges we experienced estimating random-coefficient demand models as in Berry, Levinsohn, and Pakes (1995) using two well-known data sets and a thorough optimization design. The optimization algorithms often converge at points where the first- and second-order optimality conditions fail. There are also cases of convergence at local optima. On convergence, the variation in the values of the parameter estimates translates into variation in the models' economic predictions. Price elasticities and changes in consumer and producer welfare following hypothetical merger exercises vary at least by a factor of 2 and up to a factor of 5.
Object use in childhood: development and possible functions
Authors: Pellegrini Anthony D. 
Published: May 2013

The ways in which children use objects is central to many theories of development, yet we lack systematic descriptions of the various ways in which objects are used across childhood. In this paper, I first describe the different forms of object use (i.e., exploration, construction, play, tool use and tool making) for males and females in childhood, then establish time budgets for each type of object use. Second, I make functional inferences about each form of object use and the social contexts in which each is embedded. I suggest that putative functions of object play, specifically, may be related to children’s discovery of novel uses for objects, as well as peer group centrality in abundant niches. These dynamics produce a connected social network in which object play and group structure might interact to spread novel ideas.
Towards Assessing NARCCAP Regional Climate Model Credibility for the North American Monsoon: Current Climate Simulations
Authors: Bukovsky Melissa S. , Gochis David J. , Mearns Linda O. 
Published: May 2013

AbstractThe authors examine 17 dynamically downscaled simulations produced as part of the North American Regional Climate Change Assessment Program (NARCCAP) for their skill in reproducing the North American monsoon system. The focus is on precipitation and the drivers behind the precipitation biases seen in the simulations of the current climate. Thus, a process-based approach to the question of model fidelity is taken in order to help assess confidence in this suite of simulations.The results show that the regional climate models (RCMs) forced with a reanalysis product and atmosphere-only global climate model (AGCM) time-slice simulations perform reasonably well over the core Mexican and southwest United States regions. Some of the dynamically downscaled simulations do, however, have strong dry biases in Arizona that are related to their inability to develop credible monsoon flow structure over the Gulf of California. When forced with different atmosphere–ocean coupled global climate models (AOGCMs) for the current period, the skill of the RCMs subdivides largely by the skill of the forcing or “parent” AOGCM. How the inherited biases affect the RCM simulations is investigated. While it is clear that the AOGCMs have a large influence on the RCMs, the authors also demonstrate where the regional models add value to the simulations and discuss the differential credibility of the six RCMs (17 total simulations), two AGCM time slices, and four AOGCMs examined herein. It is found that in-depth analysis of parent GCM and RCM scenarios can identify a meaningful subset of models that can produce credible simulations of the North American monsoon precipitation.
Celiac Disease in Patients With Type 1 Diabetes
Authors: Simpson Suzanne M. , Ciaccio Edward J. , Case Shelley , Jaffe Nancee , Mahadov Srihari , Lebwohl Benjamin , Green Peter H. 
Published: May 2013

Objective The purpose of this study was to investigate screening practices for celiac disease in patients with type 1 diabetes across North America. The research question investigated was whether diabetes centers screen for celiac disease in type 1 diabetes more frequently than other facilities. Research Design and Methods A survey with 27 questions on screening practices for celiac disease in patients with type 1 diabetes was designed by experts in celiac disease and diabetes. Surveys were sent by email to diabetes educators and dietitians throughout the United States and Canada between December 2010 and May 2011. Results There were 514 respondents from 484 endocrine clinics, diabetes clinics, private practices, community nutrition centers, and inpatient centers. Thirty-five percent of work locations screened for celiac disease, with endocrine clinics reporting screening at the highest frequency (80%). Tissue transglutaminase was the most common screening test used. The most frequently recommended treatment of confirmed celiac disease was a gluten-free diet. However, only 71% of respondents recommended biopsy in patients with positive serologies. Most respondents (55.3%) reported that the gluten-free diet resulted in symptom improvement in the majority of patients. Conclusions Staff at endocrine clinics were more likely to suggest screening for celiac disease in patients with type 1 diabetes. Both low screening frequency as well as inconsistency in management of positive celiac disease serological tests indicated an increase in education regarding celiac disease in patients with type 1 diabetes is required. In addition uniform guidelines should be developed.
Lacrimal neuralgia: So far, a missing cranial neuralgia
Authors: Pareja Juan A , Cuadrado María-Luz 
Published: May 2013

Background The lacrimal nerve supplies the lacrimal gland, the lateral upper eyelid, and a small cutaneous area adjacent to the external canthus. First division trigeminal neuralgia, supraorbital/supratrochlear neuralgia, and infraorbital neuralgia have been acknowledged as neuralgic causes of pain in the forehead and periorbit. However, the lacrimal nerve has never been identified as a source of facial pain. Here we report two cases of lacrimal neuralgia. Case reports A 66-year-old woman had continuous pain in the lateral aspect of her left superior eyelid and an adjacent area of the temple since age 64. A 33-year-old woman suffered from continuous pain in a small area next to the lateral canthus of her left eye since age 25. In both patients the superoexternal edge of the orbit was tender. In addition, sensory dysfunction could be demonstrated within the painful area. Anaesthetic blockades of the lacrimal nerve with lidocaine 2% resulted in complete but short-lasting relief. Pregabalin provided a complete response in the first patient. The second patient was refractory to various oral and topical drugs and different radiofrequency procedures, but she eventually obtained partial relief with pregabalin. Conclusions Lacrimal neuralgia should be considered among the neuralgic causes of orbital and periorbital pain.
Parp-2 is required to maintain hematopoiesis following sublethal γ-irradiation in mice
Authors: Farrés Jordi , Martín-Caballero Juan , Martínez Carlos , Lozano Juan J. , Llacuna Laura , Ampurdanés Coral , Ruiz-Herguido Cristina , Dantzer Françoise , Schreiber Valérie , Villunger Andreas , Bigas Anna , Yélamos José 
Published: May 2013

Key Points
Genetic inactivation of Parp-2 in mice, but not of Parp-1, resulted in bone marrow failure in response to sublethal γ-irradiation dose. Parp-2 plays an essential role in the DNA damage response in HSPC maintaining hematopoietic homeostasis under stress conditions.
Enhanced-affinity murine T-cell receptors for tumor/self-antigens can be safe in gene therapy despite surpassing the threshold for thymic selection
Authors: Schmitt Thomas M. , Aggen David H. , Stromnes Ingunn M. , Dossett Michelle L. , Richman Sarah A. , Kranz David M. , Greenberg Philip D. 
Published: May 2013

Key Points
High-affinity tumor/self antigen-specific TCRs that surpass the threshold for normal thymic selection can be safe for TCR gene therapy. T cells that express endogenous TCRs that are self-reactive can survive in the periphery with diminished TCR expression levels.
Umbilical cord blood transplantation: the first 25 years and beyond
Authors: Ballen Karen K. , Gluckman Eliane , Broxmeyer Hal E. 
Published: May 2013

Abstract
Umbilical cord blood is an alternative hematopoietic stem cell source for patients with hematologic diseases who can be cured by allogeneic hematopoietic cell transplantation. Initially, umbilical cord blood transplantation was limited to children, given the low cell dose infused. Both related and unrelated cord blood transplants have been performed with high rates of success for a variety of hematologic disorders and metabolic storage diseases in the pediatric setting. The results for adult umbilical cord blood transplantation have improved, with greater emphasis on cord blood units of sufficient cell dose and human leukocyte antigen match and with the use of double umbilical cord blood units and improved supportive care techniques. Cord blood expansion trials have recently shown improvement in time to engraftment. Umbilical cord blood is being compared with other graft sources in both retrospective and prospective trials. The growth of the field over the last 25 years and the plans for future exploration are discussed.
A new monoid construction under crossed products
Authors: Emin Ahmet , Ateş Fırat , Ikikardeş Sebahattin , Cangül Ismail Naci 
Published: May 2013

Abstract
In this paper we define a new monoid construction under crossed products for given monoids. We also present a generating set and a relator set for this product. Finally, we give the necessary and sufficient conditions for the regularity of it.

MSC:05C10, 05C12, 05C25, 20E22, 20M05.
Some new integral inequalities on time scales containing integration on infinite intervals
Authors: Meng Zhaowei , Zheng Bin , Wen Chuanbao 
Published: May 2013

Abstract
In this paper, some new Gronwall-Bellman type integral inequalities on time scales containing integration on infinite intervals are established. They provide new bounds for unknown functions concerned and can be used as a handy tool in the research of qualitative and quantitative properties of solutions of certain dynamic equations on time scales.

MSC:26E70, 26D15, 26D10.
Caspase-2 is involved in cell death induction by taxanes in breast cancer cells
Authors: Jelínek Michael , Balušíková Kamila , Kopperová Dana , Němcová-Fürstová Vlasta , Šrámek Jan , Fidlerová Julie , Zanardi Ilaria , Ojima Iwao , Kovář Jan 
Published: May 2013

Abstract

Background
We studied the role of caspase-2 in apoptosis induction by taxanes (paclitaxel, novel taxane SB-T-1216) in breast cancer cells using SK-BR-3 (nonfunctional p53, functional caspase-3) and MCF-7 (functional p53, nonfunctional caspase-3) cell lines.

Results
Both taxanes induced apoptosis in SK-BR-3 as well as MCF-7 cells. Caspase-2 activity in SK-BR-3 cells increased approximately 15-fold within 48 h after the application of both taxanes at the death-inducing concentration (100 nM). In MCF-7 cells, caspase-2 activity increased approximately 11-fold within 60 h after the application of taxanes (300 nM). Caspase-2 activation was confirmed by decreasing levels of procaspase-2, increasing levels of cleaved caspase-2 and the cleavage of caspase-2 substrate golgin-160. The inhibition of caspase-2 expression using siRNA increased the number of surviving cells more than 2-fold in MCF-7 cells, and at least 4-fold in SK-BR-3 cells, 96 h after the application of death-inducing concentration of taxanes. The inhibition of caspase-2 expression also resulted in decreased cleavage of initiator caspases (caspase-8, caspase-9) as well as executioner caspases (caspase-3, caspase-7) in both cell lines after the application of taxanes. In control cells, caspase-2 seemed to be mainly localized in the nucleus. After the application of taxanes, it was released from the nucleus to the cytosol, due to the long-term disintegration of the nuclear envelope, in both cell lines. Taxane application led to some formation of PIDDosome complex in both cell lines within 24 h after the application. After taxane application, p21WAF1/CIP1 expression was only induced in MCF-7 cells with functional p53. However, taxane application did not result in a significant increase of PIDD expression in either SK-BR-3 or MCF-7 cells. The inhibition of RAIDD expression using siRNA did not affect the number of surviving SK-BR-3 and MCF-7 cells after taxane application at all.

Conclusion
Caspase-2 is required, at least partially, for apoptosis induction by taxanes in tested breast cancer cells. We suggest that caspase-2 plays the role of an apical caspase in these cells. Caspase-2 seems to be activated via other mechanism than PIDDosome formation. It follows the release of caspase-2 from the nucleus to the cytosol.
Update on the Kelch-like (KLHL) gene family
Authors: Dhanoa Bajinder S , Cogliati Tiziana , Satish Akhila G , Bruford Elspeth A , Friedman James S 
Published: May 2013

Abstract
The Kelch-like (KLHL) gene family encodes a group of proteins that generally possess a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. BTB domains facilitate protein binding and dimerization. The BACK domain has no known function yet is of functional importance since mutations in this domain are associated with disease. Kelch domains form a tertiary structure of β-propellers that have a role in extracellular functions, morphology, and binding to other proteins. Presently, 42 KLHL genes have been classified by the HUGO Gene Nomenclature Committee (HGNC), and they are found across multiple human chromosomes. The KLHL family is conserved throughout evolution. Phylogenetic analysis of KLHL family members suggests that it can be subdivided into three subgroups with KLHL11 as the oldest member and KLHL9 as the youngest. Several KLHL proteins bind to the E3 ligase cullin 3 and are known to be involved in ubiquitination. KLHL genes are responsible for several Mendelian diseases and have been associated with cancer. Further investigation of this family of proteins will likely provide valuable insights into basic biology and human disease.
Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model
Authors: Hossain Md Munir , Cao Mingju , Wang Qi , Kim Ji Young , Schellander Karl , Tesfaye Dawit , Tsang Benjamin K 
Published: May 2013

AbstractBackgroundThe polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine condition characterized by hyperandrogenism, hyperinsulinemia, insulin resistance and chronic anovulation. Regulation and interaction of a multitude of genes required for follicular development are found to be altered in PCOS. MicroRNAs (miRNAs) mediate posttranscriptional gene regulation by binding to the 3´ untranslated region of mRNAs to either inhibit or enhance translation. However, the extent and regulation of miRNA expression in PCOS is poorly understood and the current study is the first to describe altered expression of miRNAs in PCOS.MethodsA chronically androgenized [5α-dihydrotestosterone (DHT)-treated] rat model which recapitulates many of the phenotypes of human PCOS, and miRNA PCR array was used to investigate the expression of 349 miRNAs in DHT treated rat ovaries. The ovarian expression of several selected miRNAs was also analyzed by in situ localization experiment.ResultsDHT-treated rats exhibit increased body weight, disrupted estrus cyclicity, decreased insulin sensitivity and decreased ovarian weight, with the latter phenomenon readily rescued by gonadotropin treatment in vivo. In general, 24% of the 349 miRNAs investigated were found to be differentially expressed between DHT-treated and control rats. Most of the differentially expressed miRNAs were found to be predominantly localized in the theca cells of the follicles. In silico analysis of the potential target genes of dysregulated miRNAs revealed their possible involvement in various pathways in the regulation of ovarian function.ConclusionOur current findings suggest that miRNAs are differentially regulated in hyperandrogenism, a condition possibly involved in the dysregulation of steroid hormone receptors and intra-ovarian factors, and that miRNAs may be involved in the etiology of PCOS.
Regulation of DNA transposition by CpG methylation and chromatin structure in human cells
Authors: Jursch Tobias , Miskey Csaba , Izsvák Zsuzsanna , Ivics Zoltán 
Published: May 2013

Abstract

Background
The activity of transposable elements can be regulated by different means. DNA CpG methylation is known to decrease or inhibit transpositional activity of diverse transposons. However, very surprisingly, it was previously shown that CpG methylation of the Sleeping Beauty (SB) transposon significantly enhanced transposition in mouse embryonic stem cells.

Results
In order to investigate the unexpected response of SB transposition to CpG methylation, related transposons from the Tc1/mariner superfamily, that is, Tc1, Himar1, Hsmar1, Frog Prince (FP) and Minos were tested to see how transposition was affected by CpG methylation. A significant increase of >20-fold in transposition of SB, FP and Minos was seen, whereas Tc1, Himar1 and Hsmar1 showed no difference in transposition upon CpG-methylation. The terminal inverted repeats (TIRs) of the SB, FP and Minos elements share a common structure, in which each TIR contains two functionally important binding sites for the transposase (termed the IR/DR structure). The group of IR/DR elements showed increased excision after CpG methylation compared to untreated transposon donor plasmids. We found that de novo CpG methylation is not required for transposition. A mutated FP donor plasmid with depleted CpG sites in both TIRs was as efficient in transposition as the wild-type transposon, indicating that CpG sites inside the TIRs are not responsible for altered binding of factors potentially modulating transposition. By using an in vivo one-hybrid DNA-binding assay in cultured human cells we found that CpG methylation had no appreciable effect on the affinity of SB transposase to its binding sites. However, chromatin immunoprecipitation indicated that CpG-methylated transposon donor plasmids are associated with a condensed chromatin structure characterized by trimethylated histone H3K9. Finally, DNA compaction by protamine was found to enhance SB transposition.

Conclusions
We have shown that DNA CpG methylation upregulates transposition of IR/DR elements in the Tc1/mariner superfamily. CpG methylation provokes the formation of a tight chromatin structure at the transposon DNA, likely aiding the formation of a catalytically active complex by facilitating synapsis of sites bound by the transposase.
The impact of vascular anastomosis time on early kidney transplant outcomes
Authors: Marzouk Karim , Lawen Joseph , Alwayn Ian , Kiberd Bryce A 
Published: May 2013

Abstract

Background
Most studies have found cold ischemic time to be an important predictor of delayed graft function in kidney transplantation. Relatively less is known about the warm time associated with vascular anastomosis and early outcomes.

Methods
A retrospective cohort of 298 consecutive solitary deceased donor kidney recipients from January 2006 to August 2012 was analyzed to examine the association between anastomosis time and delayed graft function (need for dialysis) and length of hospital stay.

Results
Delayed graft function (DGF) was observed in 56 patients (18.8%). The median anastomosis time was 30 minutes (interquartile range 24, 45 minutes). Anastomosis time was independently associated with DGF in a multivariable, binary logistic regression analysis (odds Ratio (OR) 1.037 per minute, 95% CI 1.016, 1.057, P = 0.001). An anastomosis time >29 minutes was also associated with a 3.5 fold higher (OR 3.5, 95% CI 1.6, 7.3, P = 0.001) risk of DGF. Median days in hospital was 9 (interquartile range 7, 14 days). Every 5 minutes of longer anastomosis time (0.20 days per minute, 95% CI 0.13, 0.27, P <0.001) was associated with 1 extra day in hospital in a multivariable linear regression model. An anastomosis time >29 minutes was associated with 3.8 (95% CI 1.6, 6.0, P <0.001) more days in hospital.

Conclusion
Anastomosis time may be an underappreciated but modifiable variable in dictating use of hospital resources. The impact of anastomosis time on longer term outcomes deserves further study.