bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuronal c-Abl activation leads to induction of cell cycle and interferon signaling pathways
Authors: Schlatterer Sarah D , Suh Hyeon-sook , Conejero-Goldberg Concepcion , Chen Shufen , Acker Christopher M , Lee Sunhee C , Davies Peter 
Published: September 2012

Abstract

Background
Expression of active c-Abl in adult mouse forebrain neurons in the AblPP/tTA mice resulted in severe neurodegeneration, particularly in the CA1 region of the hippocampus. Neuronal loss was preceded and accompanied by substantial microgliosis and astrocytosis. In contrast, expression of constitutively active Arg (Abl-related gene) in mouse forebrain neurons (ArgPP/tTA mice) caused no detectable neuronal loss or gliosis, although protein expression and kinase activity were at similar levels to those in the AblPP/tTA mice.

Methods
To begin to elucidate the mechanism of c-Abl-induced neuronal loss and gliosis, gene expression analysis of AblPP/tTA mouse forebrain prior to development of overt pathology was performed. Selected results from gene expression studies were validated with quantitative reverse transcription PCR , immunoblotting and bromodeoxyuridine (BrdU) labeling, and by immunocytochemistry.

Results
Two of the top pathways upregulated in AblPP/tTA mice with c-Abl expression for 2 weeks were cell cycle and interferon signaling. However, only the expression of interferon signaling pathway genes remained elevated at 4 weeks of c-Abl induction. BrdU incorporation studies confirm that, while the cell cycle pathway is upregulated in AblPP/tTA mice at 2 weeks of c-Abl induction, the anatomical localization of the pathway is not consistent with previous pathology seen in the AblPP/tTA mice. Increased expression and activation of STAT1, a known component of interferon signaling and interferon-induced neuronal excitotoxicity, is an early consequence of c-Abl activation in AblPP/tTA mice and occurs in the CA1 region of the hippocampus, the same region that goes on to develop severe neurodegenerative pathology and neuroinflammation. Interestingly, no upregulation of gene expression of interferons themselves was detected.

Conclusions
Our data suggest that the interferon signaling pathway may play a role in the pathologic processes caused by c-Abl expression in neurons, and that the AblPP/tTA mouse may be an excellent model for studying sterile inflammation and the effects of interferon signaling in the brain.
Individualized, discrete event, simulations provide insight into inter- and intra-subject variability of extended-release, drug products
Authors: Kim Sean HJ , Jackson Andre J , Hur Rim , Hunt C Anthony 
Published: September 2012

Abstract

Objective
Develop and validate particular, concrete, and abstract yet plausible in silico mechanistic explanations for large intra- and interindividual variability observed for eleven bioequivalence study participants. Do so in the face of considerable uncertainty about mechanisms.

Methods
We constructed an object-oriented, discrete event model called subject (we use small caps to distinguish computational objects from their biological counterparts). It maps abstractly to a dissolution test system and study subject to whom product was administered orally. A subject comprises four interconnected grid spaces and event mechanisms that map to different physiological features and processes. Drugs move within and between spaces. We followed an established, Iterative Refinement Protocol. Individualized mechanisms were made sufficiently complicated to achieve prespecified Similarity Criteria, but no more so. Within subjects, the dissolution space is linked to both a product-subject Interaction Space and the GI tract. The GI tract and Interaction Space connect to plasma, from which drug is eliminated.

Results
We discovered parameterizations that enabled the eleven subject simulation results to achieve the most stringent Similarity Criteria. Simulated profiles closely resembled those with normal, odd, and double peaks. We observed important subject-by-formulation interactions within subjects.

Conclusion
We hypothesize that there were interactions within bioequivalence study participants corresponding to the subject-by-formulation interactions within subjects. Further progress requires methods to transition currently abstract subject mechanisms iteratively and parsimoniously to be more physiologically realistic. As that objective is achieved, the approach presented is expected to become beneficial to drug development (e.g., controlled release) and to a reduction in the number of subjects needed per study plus faster regulatory review.
Understanding health systems, health economies and globalization: the need for social science perspectives
Authors: Murray Susan F , Bisht Ramila , Baru Rama , Pitchforth Emma 
Published: September 2012

Abstract
The complex relationship between globalization and health calls for research from many disciplinary and methodological perspectives. This editorial gives an overview of the content trajectory of the interdisciplinary journal ‘Globalization and Health’ over the first six years of production, 2005 to 2010. The findings show that bio-medical and population health perspectives have been dominant but that social science perspectives have become more evident in recent years. The types of paper published have also changed, with a growing proportion of empirical studies. A special issue on ‘Health systems, health economies and globalization: social science perspectives’ is introduced, a collection of contributions written from the vantage points of economics, political science, psychology, sociology, business studies, social policy and research policy. The papers concern a range of issues pertaining to the globalization of healthcare markets and governance and regulation issues. They highlight the important contribution that can be made by the social sciences to this field, and also the practical and methodological challenges implicit in the study of globalization and health.
Identifying associations between pig pathologies using a multi-dimensional machine learning methodology
Authors: Sanchez-Vazquez Manuel J , Nielen Mirjam , Edwards Sandra A , Gunn George J , Lewis Fraser I 
Published: September 2012

Abstract

Background
Abattoir detected pathologies are of crucial importance to both pig production and food safety. Usually, more than one pathology coexist in a pig herd although it often remains unknown how these different pathologies interrelate to each other. Identification of the associations between different pathologies may facilitate an improved understanding of their underlying biological linkage, and support the veterinarians in encouraging control strategies aimed at reducing the prevalence of not just one, but two or more conditions simultaneously.

Results
Multi-dimensional machine learning methodology was used to identify associations between ten typical pathologies in 6485 batches of slaughtered finishing pigs, assisting the comprehension of their biological association. Pathologies potentially associated with septicaemia (e.g. pericarditis, peritonitis) appear interrelated, suggesting on-going bacterial challenges by pathogens such as Haemophilus parasuis and Streptococcus suis. Furthermore, hepatic scarring appears interrelated with both milk spot livers (Ascaris suum) and bacteria-related pathologies, suggesting a potential multi-pathogen nature for this pathology.

Conclusions
The application of novel multi-dimensional machine learning methodology provided new insights into how typical pig pathologies are potentially interrelated at batch level. The methodology presented is a powerful exploratory tool to generate hypotheses, applicable to a wide range of studies in veterinary research.
Foot health education for people with rheumatoid arthritis — some patient perspectives
Authors: Graham Andrea S , Hammond Alison , Walmsley Steven , Williams Anita E 
Published: September 2012

AbstractBackgroundPatient education is an important component of foot health management for people with rheumatoid arthritis (RA). The content and strategies for delivery require investigation in relation to the patients' needs. This study explores patients' experiences of foot health education, to inform how the patients' needs could be identified in clinical practice and inform effective education delivery.MethodA focus group was used to collect data. The dialogue was recorded digitally, transcribed verbatim and analysed using a structured thematic approach. Member checking and peer review added to credibility of the data.Six themes emerged; (i) content and purpose of patient education – what it should be, (ii) content of patient education – what it should not be, (iii) timing of information on foot health, (iv) method of delivery, (v) ability to engage with foot health education and (vi) the patient/practitioner relationship.ConclusionsThis study identified aspects of patient education considered important by this group of patients in relation to content, timing and delivery, forming the basis for further research on clinical and patient focussed outcomes of patient education.Identifying health education needs and provision of supportive verbal and written information can foster an effective therapeutic relationship, supporting effective foot health education for people with RA.
Epigenetic alterations in preneoplastic and neoplastic lesions of the cervix
Authors: Saavedra Kathleen P , Brebi Priscilla M , Roa Juan Carlos S 
Published: September 2012

AbstractCervical cancer (CC) is one of the most malignant tumors and the second or third most common type of cancer in women worldwide. The association between human papillomavirus (HPV) and CC is widely known and accepted (99.7% of cases). At present, the pathogenesis mechanisms of CC are not entirely clear. It has been shown that inactivation of tumor suppressor genes and activation of oncogenes play a significant role in carcinogenesis, caused by the genetic and epigenetic alterations. In the past, it was generally thought that genetic mutation was a key event of tumor pathogenesis, especially somatic mutation of tumor suppressor genes. With deeper understanding of tumors in recent years, increasing evidence has shown that epigenetic silencing of those genes, as a result of aberrant hypermethylation of CpG islands in promoters and histone modification, is essential to carcinogenesis and metastasis. The term epigenetics refers to heritable changes in gene expression caused by regulation mechanisms, other than changes in DNA sequence. Specific epigenetic processes include DNA methylation, chromotin remodeling, histone modification, and microRNA regulations. These alterations, in combination or individually, make it possible to establish the methylation profiles, histone modification maps, and expression profiles characteristic of this pathology, which become useful tools for screening, early detection, or prognostic markers in cervical cancer. This paper reviews recent epigenetics research progress in the CC study, and tries to depict the relationships between CC and DNA methylation, histone modification, as well as microRNA regulations.
Phase-field modelling of microstructure evolution during processing of cold-rolled dual phase steels
Authors: Rudnizki Jenny , Prahl Ulrich , Bleck Wolfgang 
Published: September 2012

AbstractCold-rolled dual-phase steels, which belong to the advanced high strength steels, have gained much interest within the automotive industry. The formation of dual-phase microstructure, which provides an optimal combination of strength and formability for automotive applications, occurs during intercritical annealing of cold-rolled strip. Variations in the chemical composition as well as in the heat treatment parameters influence very strongly the microstructure development and therefore the final mechanical properties of the strip. Thus, the precise control of the microstructure evolution during full processing route is required for the achievement of essential mechanical properties. The current work is focused on a through-process model on a microstructural scale for the production of dual-phase steel from cold-rolled strip, which is based on Phase-Field Method and combines the description of ferrite recrystallisation and all phase transformations occurring during intercritical annealing. This approach will enable the prediction of final microstructure for varying composition and processing conditions, and therefore, can be used for the process development and optimisation.
Effect of pomegranate juice on paraoxonase enzyme activity in patients with type 2 diabetes
Authors: Parsaeyan Nayereh , Mozaffari–Khosravi Hassan , Mozayan Mohammad Reza 
Published: September 2012

Abstract
Objective(s)
Paraoxonase-1 (PON1), an HDL-associated enzyme, prevents lipoprotein oxidation. PON1 enzymatic activity has been shown to decrease in patients with diabetes. Paraoxonase activity. HDL capacity to bind with PON1 is possible under specific experimental conditions, such as oxidation, addition of polyphenols, or in diabetic patients with polyphenols doses. The aim of this study was the effect of pomegranate juice (PJ) on paraoxonase and arylesterase activity of PON1.

Materials and methods
Fifty patients with type 2 diabetes mellitus consumed 200 ml of PJ daily for a period of 6 weeks. Blood was collected from the patients before and after PJ consumption after 12 h of fasting. Blood sugar, total cholesterol, triglyceride, LDL- C and HDL-C were measured by colorimetric kit method. The malondialdehyde concentration (μmol/L) was determined by thiobarbituric acid (TBA) assay. Paraoxonase and arylesterase activity of PON1 enzyme were measured using paraoxone and phenylacetate as the substrates.

Results
The concentration of fasting blood sugar, total cholesterol, LDL-C and malondialdehyde significantly (p < 0.001) decreased after the intervention. Paraoxonase and arylesterase activity of PON1 significantly (p < 0.001) increased after the intervention. There were however no significant changes in serum triglyceride and HDL-C. There was a significant positive correlation between paraoxonase and arylesterase activity of PON1 and serum HDL-C concentration . A significant negative correlation was detected between paraoxonase and arylesterase activity of PON1 and FBS.

Conclusion
It can be concluded that PJ consumption as an antioxidant may have a contribution in changing fasting blood sugar, lipid profiles, lipoprotein oxidation, and PON1 activity.
ggbio: an R package for extending the grammar of graphics for genomic data
Authors: Yin Tengfei , Cook Dianne , Lawrence Michael 
Published: September 2012

AbstractWe introduce ggbio, a new methodology to visualize and explore genomics annotationsand high-throughput data. The plots provide detailed views of genomic regions,summary views of sequence alignments and splicing patterns, and genome-wide overviewswith karyogram, circular and grand linear layouts. The methods leverage thestatistical functionality available in R, the grammar of graphics and the datahandling capabilities of the Bioconductor project. The plots are specified within amodular framework that enables users to construct plots in a systematic way, and aregenerated directly from Bioconductor data structures. The ggbio R package isavailable athttp://www.bioconductor.org/packages/2.11/bioc/html/ggbio.html.
Multiple Segmental Uniparental Disomy Associated with Abnormal DNA Methylation of Imprinted Loci in Silver-Russell Syndrome
Authors: Dias Renuka P. , Bogdarina Irina , Cazier Jean-Baptiste , Buchanan Charles , Donaldson Malcolm C. , Johnston Linda B. , Hokken-Koelega Anita C. , Clark Adrian J. L. 
Published: September 2012

Background:
Silver-Russell syndrome (SRS; online inheritance in man 180860) is a low-birth-weight syndrome characterized by postnatal growth restriction and variable dysmorphic features. Although maternal uniparental disomy (UPD) of chromosome 7 and hypomethylation of H19 have been reported in up to 50% of all cases, no unifying mechanism is apparent.

Subjects and Methods:
Ten patients and their parents were studied using the Illumina GoldenGate methylation array and the Illumina 370K HumHap single-nucleotide polymorphism array to identify aberrations in DNA methylation as well as genomic changes including copy number changes and uniparental disomy events.

Results:
We found evidence of UPD events outside chromosome 7 in all patients. In up to 30% of patients with SRS, DNA methylation changes occur in imprinted gene loci outside 11p15.5 (PEG3, PLAGL1, and GRB10), not previously consistently linked with SRS. Furthermore, hypermethylation of GRB10 was associated with increased mRNA expression. In addition, 20% of patients appear to have DNA methylation abnormalities within multiple loci. Not all the imprinted loci with methylation defects were affected directly by UPD.

Conclusions:
The association of widespread UPD associated with abnormal methylation and mRNA expression in imprinted genes in SRS is consistent with the concept of UPD as an initial genomic abnormality leading to unstable DNA methylation within the regulatory network of imprinted genes. Furthermore, disruption of any one of these genes may contribute to the heterogeneous clinical spectrum of SRS.
A trade-off between natural and acquired antibody production in a reptile: implications for long-term resistance to disease
Authors: Sandmeier Franziska C. , Tracy C. Richard , Dupré Sally , Hunter Kenneth 
Published: September 2012

Summary
Vertebrate immune systems are understood to be complex and dynamic, with trade-offs among different physiological components (e.g., innate and adaptive immunity) within individuals and among taxonomic lineages. Desert tortoises (Gopherus agassizii) immunised with ovalbumin (OVA) showed a clear trade-off between levels of natural antibodies (NAbs; innate immune function) and the production of acquired antibodies (adaptive immune function). Once initiated, acquired antibody responses included a long-term elevation in antibodies persisting for more than one year. The occurrence of either (a) high levels of NAbs or (b) long-term elevations of acquired antibodies in individual tortoises suggests that long-term humoral resistance to pathogens may be especially important in this species, as well as in other vertebrates with slow metabolic rates, concomitantly slow primary adaptive immune responses, and long life-spans.
Synthesis and Characterization of Electron-accepting Nonsubstituted Tetraazaacene Derivatives
Authors: Isoda Kyosuke , Nakamura Masaharu , Tatenuma Toshinori , Ogata Hironori , Sugaya Tomoaki , Tadokoro Makoto 
Published: September 2012

Abstract
Oligoacenes are of interest as organic p-type semiconductors for use in electronic devices, but their use as n-type semiconductors is limited. N-Heteroacenes have been investigated as oligoacene-based n-type semiconductors due to their enhanced electron affinity. Herein, we report the synthesis, X-ray crystal structures, electrochemical, and field-effect transistor properties of TANC and BTANC.
Stereoselective Synthesis of α-Ylidene-β-dicarbonyl Compounds: A Mild PhI(OAc)2-mediated Dehydrogenation Process
Authors: Fan Liyan , Chen Wen , Tang Kunshan , Wu Dongbei 
Published: September 2012

Abstract
PhI(OAc)2-mediated dehydrogenation of α-alkyl-β-dicarbonyl compound has been developed to afford α-ylidene-β-dicarbonyl compounds with high stereoselectivity under mild conditions. This process provides a complementary entry to stereoselectivity for the Knoevenagel reaction.
Synthesis of High-purity Spherical Silica Nanoparticles from Powder Quartz by Improved Sol–Gel Method
Authors: Lin Jinhui , Dan Hui , Ding Yi 
Published: September 2012

Abstract
High-purity spherical silica nanoparticles have been successfully synthesized using powder quartz as silica sources in an improved sol–gel method. The effects of the modulus (molar ratio SiO2/Na2O) of sodium silicate and poly(ethylene glycol) (PEG) on the properties of silica nanoparticles were investigated. The results suggested that with the increase of modulus, the purity of silica nanoparticles increased. The higher purity (99.92 wt %) products can be obtained from the modulus of 3. Moreover, it was also found that the particle size, distribution, and dispersion significantly depend on the concentration of PEG. The silica nanoparticles with average size of 60 nm are well-dispersed and show a narrow size distribution when the PEG concentration is 2 wt %. The results suggest that it is feasible to prepare high-purity spherical silica nanoparticles using powder quartz as silica sources.
Formation and Catalysis of Mesoporous Nb–Mo Oxide Generated by the Self-assembly of Nanoparticles
Authors: Okumura Kazu , Ishida Soichiro , Kinoshita Yoshitaka , Sanada Takashi , Iida Keiko , Katada Naonobu 
Published: September 2012

Abstract
Mesoporous solid acid catalyst composed of Nb–Mo oxide was prepared via a hydrothermal synthesis employing ammonium niobium oxalate and hexaammonium heptamolybdate tetrahydrate as the precursors. The assembly of fine particles with diameters of 20–34 nm was observed by field emission–scanning electron microscopy. The Nb–Mo oxide has mesopores with diameters of 1.6–2.0 nm. It was possible to tune size of the primary particles and diameter of the mesopores by changing Mo/Nb ratio. The Nb–Mo oxide exhibited high activity in Friedel–Crafts alkylation.
Anthradifuran, a Furan Analogue of Pentacene, and Its Isomers, Exhibiting Solid-state Photoluminescence
Authors: Tsuji Hayato , Shoyama Kazutaka , Nakamura Eiichi 
Published: September 2012

Abstract
We have synthesized diphenyl-substituted anthra[2,3-b:6,7-b′]difuran, a furan analogue of pentacene, together with its isomers, anthra[2,1-b:6,5-b′]difuran and anthra[1,2-b:5,6-b′]difuran. These compounds are stable in the solid state with high decomposition temperatures. They are luminescent in the solid state with a quantum yield of 0.093–0.23.
Direct Geometric Observation of an Agar Gel Droplet on a Multipillar Surface
Authors: Tanaka Tomoya , Mayama Hiroyuki , Nonomura Yoshimune 
Published: September 2012

Abstract
We successfully determined the three-dimensional structure of agar gel droplets on multipillared surfaces. The contact angle, length of penetration of the agar gel into the interspace between pillars, and curvature of the bottom surface of the droplets were changed with respect to changes in the volume and concentration of the aqueous agar solution and the distance between the surface-bound pillars.