bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt/β-Catenin Signaling Is Required to Rescue Midbrain Dopaminergic Progenitors and Promote Neurorepair in Ageing Mouse Model of Parkinson’s Disease
Authors: L’Episcopo Francesca , Tirolo Cataldo , Testa Nunzio , Caniglia Salvatore , Morale Maria Concetta , Serapide Maria Francesca , Pluchino Stefano , Marchetti Bianca 
Published: March 2014

AbstractWnt/β-catenin signaling is required for specification and neurogenesis of midbrain dopaminergic (mDA) neurons, the pivotal neuronal population that degenerates in Parkinson’s disease (PD), and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Wnt/β-catenin signaling plays a vital role in adult neurogenesis but whether it might engage DA neurogenesis/neurorepair in the affected PD brain is yet unresolved. Recently, the adult midbrain aqueduct periventricular regions (Aq-PVRs) were shown to harbor multipotent clonogenic neural stem/progenitor cells (mNPCs) with DA potential in vitro, but restrictive mechanisms in vivo are believed to limit their DA regenerative capacity. Using in vitro mNPC culture systems we herein demonstrate that aging is one most critical factor restricting mNPC neurogenic potential via dysregulation of Wnt/β-catenin signaling. Coculture paradigms between young/aged (Y/A) mNPCs and Y/A astrocytes identified glial age and a decline of glial-derived factors including Wnts as key determinants of impaired neurogenic potential, whereas Wnt activation regimens efficiently reversed the diminished proliferative, neuronal, and DA differentiation potential of A-mNPCs. Next, in vivo studies in wild (Wt) and transgenic β-catenin reporter mice uncovered Wnt/β-catenin signaling activation and remarkable astrocyte remodeling of Aq-PVR in response to MPTP-induced DA neuron death. Spatio-temporal analyses unveiled β-catenin signaling in predopaminergic (Nurr1+/TH−) and imperiled or rescuing DAT+ neurons during MPTP-induced DA neuron injury and self-repair. Aging inhibited Wnt signaling, whereas β-catenin activation in situ with a specific GSK-3β antagonist promoted a significant degree of DA neurorestoration associated with reversal of motor deficit, with implications for neurorestorative approaches in PD. Stem Cells 2014;32:2147–2163
Variable selection usingLqpenalties
Authors: Qiao Xingye 
Published: March 2014

High‐dimensional data analysis emerges in many different areas of scientific research and social practice. Variable selection is an important task in statistical analysis for high‐dimensional data. The traditional all‐subset‐selection method can be ideal for variable selection, but it is computationally intractable in the high‐dimensional setting. In both regression and classification contexts, sparsity penalties are commonly used for the purpose of defining the complexity of the resulting model so as to achieve variable selection. The current article reviews a few important milestones and some recent works in the area of variable selection, especially those methods which useLqnorm and their variants as the penalty term. In particular, we review theLqpenalty, nonconvex penalties, among others. In ultrahigh‐dimensional data analysis, independence learning is often used for the purpose of dimension reduction. Theoretical results, methodological developments and computational innovations in regard to these methods are discussed. These variable selection techniques can be easily extended to problems beyond linear regression, such as classification, quantile regression, etc. Lastly, an interesting and promising research trend is the combination of multiple methods and we review several successful methods which fall into this category.This article is categorized under:Statistical and Graphical Methods of Data Analysis > Modeling Methods and AlgorithmsStatistical Models > Model SelectionStatistical Models > Linear Models
Object oriented computing
Authors: Virius Miroslav , Pecinovský Rudolf 
Published: March 2014

The object oriented computing model is the prevailing programming paradigm of today; contemporary programming languages like Java or C# strictly require it—and thus the programmer has no other choice than object oriented computing. Object oriented computing in the mainstream programming languages is based on the class concept and we adhere to this approach. The classes are user defined entities designed to describe the classes of objects in a problem solved by a program. We explain this concept as well as the three important concepts of object oriented computing: encapsulation, inheritance and polymorphism. We also mention the UML language that serves as formal description of object oriented solutions.This article is categorized under:

Software for Computational Statistics > Software/Statistical Software
Ionic Liquid assisted Synthesis of Zeolite‐TON
Authors: Tian Yuyang , McPherson Matthew J. , Wheatley Paul S. , Morris Russell E. 
Published: March 2014

Abstract An ionic liquid assisted strategy for the synthesis of zeolitic material is reported. This strategy is a solid state synthetic method and the ionic liquid is employed as structure directing agent. A TON‐type zeolite, which contains one‐dimensional 10‐member‐ring, is successfully synthesized with the assistance of the ionic liquid, 1‐ethyl‐3‐methylimidazolium bromide. This finding improves our understanding about the challenge of ionothermally synthesizing siliceous and aluminosilicate zeolites.
Evaluation of the Interpretation of Serial Ultrasound Examinations in the Diagnosis of Deep Venous Thrombosis in Children: A Retrospective Cohort Study
Authors: Stamm Michael , Zavodni Anna , Mitchell Lesley , Bonanni John Ross , Noga Michelle 
Published: March 2014

Purpose To assess ultrasound intrascan variability and the potential error rate of serial ultrasounds in the diagnosis of deep venous thrombosis in children. Methods A retrospective cohort review of imaging results of children having at least 3 serial ultrasound examinations of the same region within a 2-month period. The results were interpreted as either (1) inadequately visualized or (2) the absence or presence of deep venous thrombosis, and were categorized by location. Serial imaging findings then were further categorized based on results and clinical information. Results Sixty-four patients and 157 vessel segments were included in the study. Deep venous thrombosis was documented in 58 patients. Concordant results were observed in 26 patients (40.1%), clot resolution in 17 patients (26.6%), clot formation in 12 patients (18.8%), and discordant results in 9 patients (14%). Twenty-one of 64 patients (32.8%) had at least 1 vessel inadequately imaged. Conclusions The inconsistency of serial ultrasound results in up to 25% of patients calls attention to the potential inaccuracy of ultrasound for diagnosis and follow-up of deep venous thrombosis in children. The high proportion of patients with at least 1 inadequately visualized vessel also highlights the limitation of ultrasound in the diagnosis of pediatric deep venous thrombosis.
How Much “Law” in Legal Studies? Approaches to Teaching Legal Research and Doctrinal Analysis in a Legal Studies Program
Authors: Kazmierski Vincent 
Published: March 2014

Abstract
This article addresses the teaching of legal research methods and doctrinal analysis within a legal studies program. I argue that learning about legal research and doctrinal analysis is an important element of legal education outside professional law schools. I start by considering the ongoing debate concerning the role of legal education both inside and outside professional law schools. I then describe the way in which the research methods courses offered by the Department of Law and Legal Studies at Carleton University attempt to reconcile the tension between “law” and legal studies. In particular, I focus on how the second-year research methods course introduces students to “traditional” legal research and doctrinal analysis within a legal studies context by deploying a number of pedagogical strategies. In so doing, the course provides students with an important foundation that allows them to embrace the multiple roles of legal education outside professional law schools.
Hindsight Effects in Dollar-Weighted Returns
Authors: Hayley Simon 
Published: March 2014

AbstractA growing number of studies use dollar-weighted (DW) returns as evidence that bad timing substantially reduces investor returns, and that consequently the equity risk premium must be considerably lower than previously thought. This paper demonstrates that this method is subject to a hindsight effect (as prior returns influence levels of new investment) and derives a technique that corrects it. The results show that for mainstream U.S. equities, DW returns are low because of this hindsight effect (bad investor timing had very little impact). Thus, low DW returns do not imply that the risk premium is correspondingly low.
Bayesian analysis of culture and PCR methods for detection of Campylobacter spp. in broiler caecal samples
Authors: ARNOLD M. E. , JONES E. M. , LAWES J. R. , VIDAL A. B. , CLIFTON-HADLEY F. A. , RODGERS J. D. , POWELL L. F. 
Published: March 2014

SUMMARYThe objective of this study was to estimate the sensitivity and specificity of a culture method and a polymerase chain reaction (PCR) method for detection of two Campylobacter species: C. jejuni and C. coli. Data were collected during a 3-year survey of UK broiler flocks, and consisted of parallel sampling of caeca from 436 batches of birds by both PCR and culture. Batches were stratified by season (summer/non-summer) and whether they were the first depopulation of the flock, resulting in four sub-populations. A Bayesian approach in the absence of a gold standard was adopted, and the sensitivity and specificity of the PCR and culture for each Campylobacter subtype was estimated, along with the true C. jejuni and C. coli prevalence in each sub-population. Results indicated that the sensitivity of the culture method was higher than that of PCR in detecting both species when the samples were derived from populations infected with at most one species of Campylobacter. However, from a mixed population, the sensitivity of culture for detecting both C. jejuni or C. coli is reduced while PCR is potentially able to detect both species, although the total probability of correctly identifying at least one species by PCR is similar to that of the culture method.
Risk factors forEscherichia coliO157 on beef cattle ranches located near a major produce production region
Authors: BENJAMIN L. A. , JAY-RUSSELL M. T. , ATWILL E. R. , COOLEY M. B. , CARYCHAO D. , LARSEN R. E. , MANDRELL R. E. 
Published: March 2014

SUMMARYOur goal was to identify climate variables and management practices associated with the presence ofE. coliO157 in rangeland cow-calf operations located in a major leafy green production region in the California Central Coast.E. coliO157 was present in 2·6% (68/2654) of faecal, 1·5% (3/204) of water and 1·1% (1/93) of sediment samples collected on eight ranches over 2.5 years. Five (62·5%) ranches were positive at least once during the study. The odds of detectingE. coliO157 in faecal samples was higher during periods of higher maximum soil temperature, higher maximum relative humidity, and larger herd sizes, but decreased as wind speed increased. Molecular subtyping of isolates from cattle faeces and streams/sediments suggested minimal movement of strains between ranches. The findings suggest thatE. coliO157 prevalence is relatively low on cow-calf ranches in this region, spatially constrained, but may vary by weather conditions and herd size.
The seroprevalence of parvovirus B19 infection in pregnant women in Sudan
Authors: ADAM O. , MAKKAWI T. , REBER U. , KIRBERG H. , EIS-HÜBINGER A. M. 
Published: March 2014

SUMMARYParvovirus B19 (B19V) infection during pregnancy may have serious consequences like fetal anaemia, hydrops fetalis, and fetal loss. Since epidemiological data on B19V infection are generally lacking in Sudan, the current study aimed to determine the seroprevalence of B19V in Sudanese pregnant women. Five hundred women, attending antenatal clinics in Khartoum state between November 2008 and March 2009, were enrolled and screened for B19V IgG and IgM antibodies by enzyme immunoassays. The study revealed a B19V IgG seroprevalence of 61·4%, with one subject positive for IgM. B19V DNA was not detected by PCR in any of the tested individuals. B19V IgG seroprevalence was significantly correlated with multigravidity (P = 0·046). Our data showed that B19V infection is prevalent in Sudan and we recommend further studies in Sudanese women, particularly in those with complications and adverse outcomes of pregnancy.
Secondary metabolite gene expression and interplay of bacterial functions in a tropical freshwater cyanobacterial bloom
Authors: Penn Kevin , Wang Jia , Fernando Samodha C , Thompson Janelle R 
Published: March 2014

Abstract
Cyanobacterial harmful algal blooms (cyanoHABs) appear to be increasing in frequency on a global scale. The Cyanobacteria in blooms can produce toxic secondary metabolites that make freshwater dangerous for drinking and recreation. To characterize microbial activities in a cyanoHAB, transcripts from a eutrophic freshwater reservoir in Singapore were sequenced for six samples collected over one day-night period. Transcripts from the Cyanobacterium Microcystis dominated all samples and were accompanied by at least 533 genera primarily from the Cyanobacteria, Proteobacteria, Bacteroidetes and Actinobacteria. Within the Microcystis population, abundant transcripts were from genes for buoyancy, photosynthesis and synthesis of the toxin microviridin, suggesting that these are necessary for competitive dominance in the Reservoir. During the day, Microcystis transcripts were enriched in photosynthesis and energy metabolism while at night enriched pathways included DNA replication and repair and toxin biosynthesis. Microcystis was the dominant source of transcripts from polyketide and non-ribosomal peptide synthase (PKS and NRPS, respectively) gene clusters. Unexpectedly, expression of all PKS/NRPS gene clusters, including for the toxins microcystin and aeruginosin, occurred throughout the day-night cycle. The most highly expressed PKS/NRPS gene cluster from Microcystis is not associated with any known product. The four most abundant phyla in the reservoir were enriched in different functions, including photosynthesis (Cyanobacteria), breakdown of complex organic molecules (Proteobacteria), glycan metabolism (Bacteroidetes) and breakdown of plant carbohydrates, such as cellobiose (Actinobacteria). These results provide the first estimate of secondary metabolite gene expression, functional partitioning and functional interplay in a freshwater cyanoHAB.
Dynamics of adenylate cyclase regulation via heterotrimeric G-proteins
Authors: Milde Markus , Werthmann Ruth C. , von Hayn Kathrin , Bünemann Moritz 
Published: March 2014

A wide variety of G-protein-coupled receptors either activate or inhibit ACs (adenylate cyclases), thereby regulating cellular cAMP levels and consequently inducing proper physiological responses. Stimulatory and inhibitory G-proteins interact directly with ACs, whereas Gq-coupled receptors exert their effects primarily via Ca2+. Using the FRET-based cAMP sensor Epac1 (exchange protein directly activated by cAMP 1)–cAMPS (adenosine 3′,5′-cyclic monophosphorothioate), we studied cAMP levels in single living VSMCs (vascular smooth muscle cells) or HUVECs (human umbilical vein endothelial cells) with subsecond temporal resolution. Stimulation of purinergic (VSMCs) or thrombin (HUVECs) receptors rapidly decreased cAMP levels in the presence of the β-adrenergic agonist isoprenaline via a rise in Ca2+ and subsequent inhibition of AC5 and AC6. Specifically in HUVECs, we observed that, in the continuous presence of thrombin, cAMP levels climbed slowly after the initial decline with a delay of a little less than 1 min. The underlying mechanism includes phospholipase A2 activity and cyclo-oxygenase-mediated synthesis of prostaglandins. We studied further the dynamics of the inhibition of ACs via Gi-proteins utilizing FRET imaging to resolve interactions between fluorescently labelled Gi-proteins and AC5. FRET between Gαi1 and AC5 developed at much lower concentration of agonist compared with the overall Gi-protein activity. We found the dissociation of Gαi1 subunits and AC5 to occur slower than the Gi-protein deactivation. This led us to the conclusion that AC5, by binding active Gαi1, interferes with G-protein deactivation and reassembly and thereby might sensitize its own regulation.
Insulin, incretins and other growth factors as potential novel treatments for Alzheimer's and Parkinson's diseases
Authors: Hölscher Christian 
Published: March 2014

Recently, it has been shown that in patients with AD (Alzheimer's disease) and, to some degree, in patients with PD (Parkinson's disease) insulin signalling is impaired. This finding has initiated a range of research projects that showed remarkable improvements using treatments that initially had been developed to treat diabetes. Pre-clinical studies showed good neuroprotective effects when applying insulin or long-lasting analogues of incretin peptides. In transgenic animal models of AD and PD, analogues of the incretin GLP-1 (glucagon-like peptide 1) prevented neurodegenerative processes and improved neuronal and synaptic functionality in AD and PD. Amyloid plaque load and synaptic loss as well as cognitive impairment had been ameliorated in AD models, and dopaminergic loss of transmission and motor function was reversed in models of PD. On the basis of these promising findings, several clinical trials are being conducted with the first encouraging clinical results being published. In several pilot studies in AD patients, the nasal application of insulin showed encouraging effects on cognition and biomarkers. A pilot study in PD patients testing a GLP-1 receptor agonist that is currently on the market as a treatment for Type 2 diabetes also showed encouraging effects. Several other clinical trials are currently ongoing in AD patients. The present review summarizes the range of neuroprotective effects that these drugs have demonstrated and emphasizes the great promise that this approach has in providing novel treatments that have protective and even restorative properties that no current drug treatment can offer.
Assay of methylglyoxal-derived protein and nucleotide AGEs
Authors: Rabbani Naila , Shaheen Fozia , Anwar Attia , Masania Jinit , Thornalley Paul J. 
Published: March 2014

Glyoxalase- and methylglyoxal-related research has required the development of quantitative and reliable techniques for the measurement of methylglyoxal-derived glycation adducts of protein and DNA. There are also other glycation adducts, oxidation adducts and nitration adducts of proteins and oxidation adducts of DNA. Proteolysis of protein releases glycation, oxidation and nitration free adducts (glycated, oxidized and nitrated amino acids) in plasma and nuclease digestion of DNA releases glycated and oxidized nucleosides into plasma and other body fluids for excretion in urine. The gold standard method for quantifying these adducts is stable isotopic dilution analysis LC–MS/MS. Protein and DNA adduct residues are determined by assay of enzymatic hydrolysates of protein and DNA extracts prepared using cocktails of proteases and nucleases respectively. Free adducts are determined by analysis of ultrafiltrates of plasma, urine and other physiological fluids. Protein damage markers (13 glycation adducts, five oxidation adducts and 3-nitrotyrosine) and DNA damage markers (three glycation adducts and one oxidation adduct) are quantified using 25 μg of protein, 10 μg of DNA or 5 μl of physiological fluid. Protein and nucleotide AGE (advanced glycation end-product) assay protocols resistant to interferences is described.
Einsatz einer präventiven, epikutanen Unterdrucktherapie (Prevena™) bei offener Korrektur
von Deformitäten der vorderen Brustwand reduziert das Auftreten von
Wundheilungsstörungen
Authors: Simon K. , Schulz-Drost M. , Besendörfer M. , Carbon R. , Schulz-Drost S. 
Published: March 2014

Hintergrund: Eingriffe an der vorderen Brustwand können zu Wundheilungsstörungen führen.
Untersucht wird, ob die Anwendung einer präventiven Unterdrucktherapie das Risiko einer
Wundheilungsstörung an der vorderen Brustwand nach offener Brustwandkorrektur reduzieren kann.
Methodik: In einer retrospektiven Vergleichsanalyse von 100 Patienten mit offener
Korrektur einer Trichter- oder Kielbrustdeformität in den Jahren 2010 bis 2012 wurden 50
aufeinanderfolgend behandelte Patienten, deren Wunde 5 Tage postoperativ mittels Prevena™ (KCI
Medizinprodukte GmbH, Wiesbaden) behandelt wurde, mit 50 aufeinanderfolgenden Patienten
verglichen, deren Wunde mit einer OPSITE®-Folie (Smith & Nephew, Hamburg) abgedeckt wurde.
Die Wundnaht erfolgte nach einem Standard, ebenso die Einlage von Redon-Dränagen. Es wurden
daher retrospektiv 2 gleichwertige, repräsentative Patientengruppen gebildet und systematisch
anhand standardisiert erhobener Parameter verglichen. Das Wunddressing wurde in beiden Gruppen
unmittelbar nach dem Wundverschluss aufgebracht und jeweils bis zum 5. postoperativen Tag
belassen. Wundkontrollen erfolgten bei Abnahme des Verbands, bei Entlassung, 6 Wochen und 12
Wochen postoperativ. Zu diesen Zeitpunkten wurde die Wunde auf das Vorliegen von Schwellung,
Rötung, Nässen, Schmerzen und Heilungszeichen untersucht. Gegebenenfalls vorliegende Wundfisteln
oder Dehiszenzen wurden in Lokalisation und Ausdehnung erfasst.
Ergebnisse: In der
Prevena-Gruppe sahen wir 10 % interventionspflichtige Wundheilungsstörungen, in der
OPSITE-Gruppe 24 %. Bei Anwendung der Prevena zeigten einige Patienten umschriebene
Hauterosionen im Bereich des Übergangs Schwamm-Folie. Diese waren jedoch in allen Fällen
innerhalb des Beobachtungszeitraums folgenfrei abgeheilt.
Schlussfolgerungen: Durch
Anwendung einer präventiven Vakuumtherapie konnte retrospektiv eine erhebliche Reduktion der
Rate von Wundheilungsstörungen nach offenen Brustwandkorrekturen erzielt werden. Statistisch war
jedoch kein Signifikanzniveau nachzuweisen (p = 0,074).
Exploiting polypharmacology for drug target deconvolution
Authors: Gujral Taranjit Singh , Peshkin Leonid , Kirschner Marc W. 
Published: March 2014

Significance
Protein kinase inhibitors represent a major class of anticancer drugs, which are notoriously unspecific. Efforts to exploit the polypharmacology of inhibitors for target deconvolution have met with little success. Our significant contribution is to apply regularized regression to kinase expression and kinase profiling on a large set of inhibitors. By selecting a set of optimally designed kinase inhibitors that span a broad range of kinase specificities, we identified relevant kinases from our model in six cell lines; we then empirically validated a set of specific kinases that regulate cancer cell migration. Using this model, we predict a cell type-specific response to previously untested inhibitors. Broadly, these approaches should prove useful in identifying novel targets and in rational cancer therapy.