bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterozygous disruption of Flk‐1 receptor leads to myocardial ischaemia reperfusion injury in mice: application of affymetrix gene chip analysis
Authors: Thirunavukkarasu M. , Addya S. , Juhasz B. , Pant R. , Zhan L. , Surrey S. , Maulik G. , Menon V. P. , Maulik N. 
Published: February 2008

AbstractThis study addresses an important clinical issue by identifying potential candidates of vascular endothelial growth factor (VEGF) signalling through the Flk‐1 receptor that trigger cardioprotective signals under ischaemic stress. Isolated working mouse hearts of both wild‐type (WT) and Flk‐1+/− were subjected to global ischaemia (I) for 30 min. followed by 2 hrs of reperfusion (R). Flk‐1+/− myocardium displayed almost 50% reduction in Flk‐1 mRNA as examined by quantitative real‐time RT‐PCR at the baseline level. Flk‐1+/− mouse hearts displayed reduction in left ventricular functional recovery throughout reperfusion (dp/dt 605 versus 884), after 2 hrs (P < 0.05). Coronary (1.9 versus 2.4 ml) and aortic flow (AF) (0.16 versus 1.2 ml) were reduced in Flk‐1+/− after 2 hrs of reperfusion. In addition, increased infarct size (38.4%versus 28.41%, P < 0.05) and apoptotic cardiomyocytes (495 versus 213) were observed in Flk‐1+/− knockout (KO) mice. We also examined whether ischaemic preconditioning (PC), a novel method to induce cardioprotection against ischaemia reperfusion injury, through stimulating the VEGF signalling pathway might function in Flk‐1+/− mice. We found that knocking down Flk‐1 resulted in significant reduction in the cardioprotective effect by PC compared to WT. Affymetrix gene chip analysis demonstrated down‐regulation of important genes after IR and preconditioning followed by ischaemia reperfusion in Flk‐1+/− mice compared to WT. To get insight into the underlying molecular pathways involved in ischaemic PC, we determined the distinct and overlapping biological processes using Ingenuity pathway analysis tool. Independent evidence at the mRNA level supporting the Affymetrix results were validated using real‐time RT‐PCR for selected down‐regulated genes, which are thought to play important roles in cardioprotection after ischaemic insult. In summary, our data indicated for the first time that ischaemic PC modifies genomic responses in heterozygous VEGFR‐2/Flk‐1 KO mice and abolishes its cardioprotective effect on ischaemic myocardium.
New histone deacetylase inhibitors as potential therapeutic tools for advanced prostate carcinoma
Authors: Wedel S. A. , Sparatore A. , Soldato P. D. , Al‐Batran S.‐E. , Atmaca A. , Juengel E. , Hudak L. , Jonas D. , Blaheta R. A. 
Published: February 2008

AbstractThe anti‐epileptic drug valproic acid is also under trial as an anti‐cancer agent due to its histone deacetylase (HDAC) inhibitory properties. However, the effects of valproic acid (VPA) are limited and concentrations required for exerting anti‐neoplastic effects in vitro may not be reached in tumour patients. In this study, we tested in vitro and in vivo effects of two VPA‐derivatives (ACS2, ACS33) on pre‐clinical prostate cancer models. PC3 and DU‐145 prostate tumour cell lines were treated with various concentrations of ACS2 or ACS33 to perform in vitro cell proliferation 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays and to evaluate tumour cell adhesion to endothelial cell monolayers. Analysis of acetylated histones H3 and H4 protein expression was performed by western blotting. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. Tumour sections were assessed by immunohistochemistry for histone H3 acetylation and proliferation. ACS2 and ACS33 significantly up‐regulated histone H3 and H4 acetylation in prostate cancer cell lines. In micromolar concentrations both compounds exerted growth arrest in PC3 and DU‐145 cells and prevented tumour cell attachment to endothelium. In vivo, ACS33 inhibited the growth of PC3 in subcutaneous xenografts. Immunohistochemistry and western blotting confirmed increased histone H3 acetylation and reduced proliferation. ACS2 and ACS33 represent novel VPA derivatives with superior anti‐tumoural activities, compared to the mother compound. This investigation lends support to the clinical testing of ACS2 or ACS33 for the treatment of prostate cancer.
The ubiquitin‐proteasome system in Alzheimer's disease
Authors: Oddo Salvatore 
Published: February 2008

Introduction
Biology of the UPS
The involvement of the UPS in AD pathogenesis
The UPS as a link between Aβ and tau interaction
Conclusions

AbstractAccumulation of proteins is a recurring event in many neurodegenerative diseases, including Alzheimer's disease (AD).Evidence has suggested that protein accumulation may result from a dysfunction in the ubiquitin proteasome system (UPS). Indeed, there is clear genetic and biochemical evidence of an involvement of the ubiquitin proteasome system in AD. This review summarizes the data supporting an involvement of the UPS in the pathogenesis of AD, focusing on the data showing the relationship between Aβ and tau, the two hallmark lesions of AD, and the UPS.
Delayed development of interstitial cells of Cajal in the ileum of a human case of gastroschisis
Authors: Midrio Paola , Vannucchi Maria Giuliana , Pieri Laura , Alaggio Rita , Faussone‐Pellegrini Maria Simonetta 
Published: February 2008

AbstractThe Interstitial Cells of Cajal (ICC) are responsible for rhythmic electrical activity. A paralytic ileus is present in gastroschisis (GS), a malformation due to a defective closure of the abdominal wall through which part of the intestine herniates during pregnancy. In experimental GS, ICC morphological immaturity was shown in the rat foetus at‐term but it could not be demonstrated whether differentiation is accomplished post‐natally. For this purpose we morphologically investigated ICC, as well as enteric neurons and smooth muscle cells, in a case of human GS at birth and 1 month later when peristaltic activity had initiated. A 36 weeks gestation female was born by c/section with prenatal diagnosis of GS and possible volvulus of the herniated intestine. At birth, the necrotic intestine was resected and both ileostomy and colostomy were performed. The intestine continuity was restored after 4 weeks. Intestinal specimens, taken during both operations at the level of the proximal stoma, were immunostained with c‐kit, neuron‐specific‐enolase and α‐smooth‐muscle‐actin antibodies and some processed for electron microscopy. ICC were present at the myenteric plexus only. At birth, these cells were rare and ultrastructurally immature; 1 month later, when partial enteral feeding was tolerated, they formed rows or groups and many of them were ultrastructurally differentiated. Neurons and smooth muscle cells, immature at birth, had developed after 1 month. Therefore, ICC differentiation, as well as that of neurons and smooth muscle cells, is delayed at birth and this might explain the paralytic ileus in GS. One month later, differentiation quickly proceeded at all cellular levels paralleling the increasing tolerance of enteral nutrition.
Biomarker candidates for cardiovascular disease and bone metabolism disorders in chronic kidney disease: a systems biology perspective
Authors: Perco Paul , Wilflingseder Julia , Bernthaler Andreas , Wiesinger Martin , Rudnicki Michael , Wimmer Barbara , Mayer Bernd , Oberbauer Rainer 
Published: February 2008

Introduction
Kidney disease and cardiovascular risk
Kidney disease and bone metabolism disorders
Data integration and systems biology analyses
Conclusion and outlook
AbstractPatients with chronic kidney disease (CKD) show a panel of partially de‐regulated serum markers indicative for bone metabolism disorders and cardiovascular diseases (CVDs). This review provides an overview of currently reported biomarker candidates at the interface of kidney disease, bone metabolism disorders and CVDs, and gives details on their functional interplay on the level of protein–protein interaction data. We retrieved 13 publications from 1999 to 2006 reporting 31 genes associated with CVDs, and 46 genes associated with bone metabolism disorders in patients with CKD. We identified these genes to be functionally involved in signal transduction processes, cell communication, immunity and defence, as well as skeletal development. On the basis of the given set of 77 genes further 276 interacting proteins were identified using reference data on known protein interactions. Their functional interplay was estimated by linking properties reflected by gene expression data characterizing CKD, gene ontology terms as provided by the gene ontology consortium and transcription factor binding site profiles. Highly connected sub‐networks of proteins associated with CKD, CVDs or bone metabolism disorders were detected involving proteins like collagens (COL1A1, COL1A2), fibronectin, transforming growth factor‐β1, or components of fibrinogen (FG‐α, FG‐β, FG‐γ). A systems biology approach provides a methodological framework for linking singular biomarker candidates towards deriving functional dependencies among clinically interlinked diseases.
Apolipoprotein E genotype and risk for development of cataract and age‐related macular degeneration
Authors: Utheim Øygunn A. , Ritland Jon Ståle , Utheim Tor P. , Espeseth Thomas , Lydersen Stian , Rootwelt Helge , Semb Svein Ove , Elsås Tor 
Published: February 2008

Abstract.Purpose:  To study whether apolipoprotein E (APOE) genotypes are associated with risk for developing cataract and age‐related macular degeneration (AMD).Methods:  A sample of 88 healthy adults (50–75 years) genotyped for polymorphisms of APOE underwent an eye examination which included visual acuity (VA) testing, slit‐lamp cataract evaluation, optical coherence tomography (OCT) and fundus photography, the last of which was analysed and graded for macular pathology at the Reading Centre, Moorfields Eye Hospital, London. Two‐by‐two cross tables were analysed using the Fisher–Boschloo unconditional full multinomial test. Two‐sample t‐tests were used for comparing means of scale variables.Results:  Thirty‐two participants were diagnosed with cataract or had undergone cataract surgery in one or both eyes, and 56 participants demonstrated no signs of cataract. We found that APOE4 carriers were less likely to have cataract than non‐APOE4 carriers (p = 0.039). No correlation between APOE genotypes and morphologic changes in the macular region was revealed. However, APOE3 carriers disclosed significantly higher average macular thickness in both eyes than non‐APOE3 carriers (p = 0.012), and APOE3 carriers also had significantly better VA than non‐APOE3 carriers (p = 0.041).Conclusions:  We found no association between AMD and APOE polymorphism in a population of 96 individuals aged 50−75 years. A weak negative association between APOE4 and cataract was uncovered in the same population. Apolipoprotein E3 may be a protective factor against the loss of nerve fibres in the macular region.
Ultrasound biomicroscopy of zonular anatomy in clinically unilateral exfoliation syndrome
Authors: Sbeity Zaher , Dorairaj Syril K. , Reddy Swathi , Tello Celso , Liebmann Jeffrey M. , Ritch Robert 
Published: February 2008

Abstract.Purpose:  To evaluate the ability of ultrasound biomicroscopy (UBM) to detect abnormalities in the zonular apparatus in unaffected eyes of patients with clinically unilateral exfoliation syndrome (XFS) using a standardized grading system.Methods:  The affected and unaffected eyes of 17 patients with clinically unilateral XFS and 17 eyes of 17 control subjects underwent UBM. Radial sections detailing the lens and zonules at 12:00, 1:30, 3:00, 4:30, 6:00, 7:30, 9:00 and 10:30 clock hours were obtained. The images were graded by a masked, experienced UBM observer using a standardized scoring system based on the zonular appearance (0, none; 1 and 2, uneven or disrupted zonules with or without patchy deposits; 3, diffuse granulation, thick zonules or both; 4, total zonular disruption). Affected meridians were compared by the Friedman test, while distributions of unaffected and affected eyes were compared using the Student t‐test.Results:  In the control group, 15/17 eyes showed normal zonules; the remaining two eyes showed grade 1 changes in some meridians. The mean grade score was 0.33 [standard deviation (SD) 0.84]. Eyes with XFS had a higher score than control eyes, with a mean score of 14.35 (SD 7.14, P < 0.001, Student t‐test). In clinically unaffected fellow eyes, the mean score was 10.53 (SD 7.44), and was less than that of XFS eyes (P = 0.008, Student t‐test). Twelve XFS eyes (71%) and six unaffected fellow eyes (35%) had grade 3 or 4 in at least one meridian (P = 0.07, Friedman test).Conclusion:  Bilateral zonular involvement is present in subjects with clinically unilateral XFS. These zonular changes may be extensive in fellow eyes without clinically evident exfoliation material. UBM assessment of zonular status in fellow eyes prior to cataract extraction may aid in surgical planning.
The dihydropyridine isradipine inhibits the murine but not the bovine a‐wave response of the electroretinogram
Authors: Banat Mohammed , Lüke Matthias , Siapich Siarhei A. , Hescheler Jürgen , Weiergräber Marco , Schneider Toni 
Published: February 2008

Abstract.Purpose:  In order to record light‐evoked responses from photoreceptor cells and the higher neuronal retinal network, the isolated vertebrate retina represents a sensitive tool for basic research of retinal function and for testing the toxicity of ocular therapeutics. In the past, this in vitro technique was optimized for frog and bovine retina; it should be transferred now to the isolated murine retina because the model could allow for functional testing of genes involved in retinal signalling using wild‐type and gene‐inactivated mice. Thus, alterations in the electroretinogram (ERG) may reveal differences in retinal information processing because of the inactivation of a specific gene.Methods:   We used a superfused vertebrate retina assay to test bovine and murine retina.Results:  In order to evaluate the sensitivity of the ERG recording technique from the isolated murine retina, we first determined the light intensity response and the stability of the a‐wave amplitude during ERG recording, which did not differ between the species. However, testing the dihydropyridine sensitivity of the a‐wave, we found that the murine a‐wave was highly sensitive towards racemic isradipine (8–25 nM) but the bovine retina a‐wave was not. A similar species‐dependent difference was observed for mibefradil (10 μM).Conclusion:  Murine and bovine retina differ with respect to transretinal signalling. At the level of photoreceptor cells, the ERG/a‐wave is modulated by isradipine‐sensitive voltage‐gated Ca2+ channels, which trigger feedback signalling to photoreceptors.
The luminosity–halo mass relation for brightest cluster galaxies
Authors: Brough S. , Couch W. J. , Collins C. A. , Jarrett T. , Burke D. J. , Mann R. G. 
Published: February 2008

Abstract
We examine the central galaxy luminosity–host halo mass relation for 54 brightest group galaxies (BGGs) and 92 brightest cluster galaxies (BCGs) at z &lt; 0.1 and present the first measurement of this relation for a sample of known BCGs at . At z &lt; 0.1 we find LK∝M0.24±0.08200 for the BCGs and the early-type BGGs in groups with extended X-ray emission and LK∝M0.11±0.10200 for the BCGs alone. At 0.1 &lt; z &lt; 0.8 we find LK∝M0.28±0.11200. We conclude that there is no evidence for evolution in this relationship between z &lt; 0.1 and z &lt; 0.8: BCG growth appears to still be limited by the time-scale for dynamical friction at these earlier times, not proceeding according to the predictions of present semi-analytic models.
Accretion rates and beaming in ultraluminous X-ray sources
Authors: King A. R. 
Published: February 2008

Abstract
I show that extreme beaming factors b are not needed to explain ultraluminous X-ray sources (ULXs) as stellar-mass binaries. For neutron-star accretors, one typically requires b∼ 0.13, and for black holes almost no beaming (b∼ 0.8). The main reason for the high apparent luminosity is the logarithmic increase in the limiting luminosity for super-Eddington accretion. The required accretion rates are explicable in terms of thermal-time-scale mass transfer from donor stars of mass 6–10 M⊙, or possibly transient outbursts. Beaming factors ≲0.1 would be needed to explain luminosities significantly above 1040L40 erg s−1, but these requirements are relaxed somewhat if the accreting matter has low hydrogen content.
Tracking down a critical halo mass for killing galaxies through the growth of the red sequence
Authors: Gilbank David G. , Balogh Michael L. 
Published: February 2008

Abstract
Red-sequence galaxies record the history of terminated star formation in the Universe and can thus provide important clues to the mechanisms responsible for this termination. We construct composite samples of published cluster and field galaxy photometry in order to study the build-up of galaxies on the red sequence, as parametrized by the dwarf-to-giant ratio (DGR). We find that the DGR in clusters is higher than that of the field at all redshifts, implying that the faint end of the red sequence was established first in clusters. We find that the DGR evolves with redshift for both samples, consistent with the ‘down-sizing’ picture of star formation. We examine the predictions of semi-analytic models for the DGR and find that neither the magnitude of its environmental dependence nor its evolution is correctly predicted in the models. Red-sequence DGRs are consistently too high in the models, the most likely explanation being that the strangulation mechanism used to remove hot gas from satellite galaxies is too efficient. Finally, we present a simple toy model including a threshold mass, below which galaxies are not strangled, and show that this can predict the observed evolution of the field DGR.
Methodology for Comparing Source and Plume Remediation Alternatives
Authors: Falta Ronald W. 
Published: February 2008

AbstractIt is often difficult at contaminated sites to decide whether remediation effort should be focused on the contaminant source, the dissolved plume, or on both zones. The decision process at these sites is hampered by a lack of quantitative tools for comparing remediation alternatives. A new screening‐level mass balance approach is developed for simulating the transient effects of simultaneous ground water source and plume remediation. The contaminant source model is based on a power function relationship between source mass and source discharge, and it can consider partial source remediation at any time after the initial release. The source model serves as a time‐dependent mass flux boundary condition to a new analytical plume model, where flow is assumed to be one dimensional, with three‐dimensional dispersion. The plume model simulates first‐order sequential decay and production of several species, and the decay rates and parent/daughter yield coefficients are variable functions of time and distance. This new method allows for flexible simulation of natural attenuation or remediation efforts that enhance plume degradation. The plume remediation effort may be temporary or delayed in time, limited in space, and it may have different chemical effects on different contaminant species in the decay chain.
Three‐Dimensional Geostatistical Inversion of Flowmeter and Pumping Test Data
Authors: Li Wei , Englert Andreas , Cirpka Olaf A. , Vereecken Harry 
Published: February 2008

AbstractWe jointly invert field data of flowmeter and multiple pumping tests in fully screened wells to estimate hydraulic conductivity using a geostatistical method. We use the steady‐state drawdowns of pumping tests and the discharge profiles of flowmeter tests as our data in the inference. The discharge profiles need not be converted to absolute hydraulic conductivities. Consequently, we do not need measurements of depth‐averaged hydraulic conductivity at well locations. The flowmeter profiles contain information about relative vertical distributions of hydraulic conductivity, while drawdown measurements of pumping tests provide information about horizontal fluctuation of the depth‐averaged hydraulic conductivity. We apply the method to data obtained at the Krauthausen test site of the Forschungszentrum Jülich, Germany. The resulting estimate of our joint three‐dimensional (3D) geostatistical inversion shows an improved 3D structure in comparison to the inversion of pumping test data only.
Forensic Isotope Analysis to Refine a Hydrologic Conceptual Model
Authors: Bassett R.L , Steinwand Aaron , Jorat Saeed , Petersen Christian , Jackson Randy 
Published: February 2008

AbstractWater resources in the arid southwestern United States are frequently the subject of conflict from competing private and public interests. Legal remedies may remove impasses, but the technical analysis of the problem often determines the future success of legal solutions. In Owens Valley, California, the source of water for the Los Angeles Aqueduct (LAA) is flow diverted from the Owens River and its tributaries and ground water from valley aquifers. Future management of ground water delivered to the LAA needs technical support regarding quantity available, interconnection of shallow and confined aquifers, impact on local springs, and rate of recharge. Ground water flow models and ground water composition are tools already in use, but these have large uncertainty for local interpretations. This study conducted targeted sampling of springs and wells to evaluate the hydrologic system to corroborate conceptual and numerical models. The effort included measurement of intrinsic isotopic composition at key locations in the aquifers. The stable isotopic data of boron (δ11B), sulfur (δ34S), oxygen (δ18O), hydrogen (δD), and tritium (3H) supported by basic chemical data provided rules for characterizing the upper and the lower aquifer system, confirmed the interpretation of ground water flow near faults and flow barriers, and detected hydraulic connections between the LAA and the perennial springs at key locations along the unlined reach of the LAA. This study exemplifies the use of forensic isotopic approaches as independent checks on the consistency of interpretations of conceptual models of a ground water system and the numerical hydrologic simulations.
Screening of One‐Well Hydraulic Barrier Design Alternatives
Authors: Rubin Hillel , Shoemaker Christine A. , Köngeter Jürgen 
Published: February 2008

AbstractThis study develops a robust method for screening one‐well hydraulic barrier design alternatives that can be easily computed without a numerical simulation model. The paper outlines the general method and shows its implementation with hydraulic barriers using a single pumping well. For such barriers, the method is easily computable with spreadsheets and/or charts depicted within the paper and posted online. The method applies the potential flow theory, which leads to using a curvilinear coordinate system for all types of calculations. For contaminant transport calculations, the method applies the boundary layer theory. For calculations of aquifer remediation, the method refers to bulk characteristics of the domain. As an example, the method has been applied to calculate the possible containment of a wide part of the coastal plain aquifer in Israel, which is contaminated by entrapped kerosene (a light nonaqueous phase liquid).