By no means Vasilescu, Bogdan; Serebrenik, Alexander; van den Brand, Mark
Proceedings of the 2nd International Workshop on Emerging Trends in Software Metrics,
05/2011
Conference Proceeding
Fault prediction models usually employ software metrics which were previously shown to be a strong predictor for defects, e.g., SLOC. However, metrics are usually defined on a microlevel (method, ...class, package), and should therefore be aggregated in order to provide insights in the evolution at the macro-level (system). In addition to traditional aggregation techniques such as the mean, median, or sum, recently econometric aggregation techniques, such as the Gini, Theil, and Hoover indices have been proposed. In this paper we wish to understand whether the aggregation technique influences the presence and strength of the relation between SLOC and defects. Our results indicate that correlation is not strong, and is influenced by the aggregation technique.
The Popeye domain–containing 1 (
POPDC1
) gene encodes a plasma membrane–localized cAMP-binding protein that is abundantly expressed in striated muscle. In animal models, POPDC1 is an essential ...regulator of structure and function of cardiac and skeletal muscle; however,
POPDC1
mutations have not been associated with human cardiac and muscular diseases. Here, we have described a homozygous missense variant (c.602C>T, p.S201F) in POPDC1, identified by whole-exome sequencing, in a family of 4 with cardiac arrhythmia and limb-girdle muscular dystrophy (LGMD). This allele was absent in known databases and segregated with the pathological phenotype in this family. We did not find the allele in a further screen of 104 patients with a similar phenotype, suggesting this mutation to be family specific. Compared with WT protein, POPDC1
S201F
displayed a 50% reduction in cAMP affinity, and in skeletal muscle from patients, both POPDC1
S201F
and WT POPDC2 displayed impaired membrane trafficking. Forced expression of POPDC1
S201F
in a murine cardiac muscle cell line (HL-1) increased hyperpolarization and upstroke velocity of the action potential. In zebrafish, expression of the homologous mutation (
popdc1
S191F
) caused heart and skeletal muscle phenotypes that resembled those observed in patients. Our study therefore identifies
POPDC1
as a disease gene causing a very rare autosomal recessive cardiac arrhythmia and LGMD, expanding the genetic causes of this heterogeneous group of inherited rare diseases.
Abstract only
Annexin A2 has been shown to act as a receptor for plasminogen (Plg) and its tissue type activator (tPA) in endothelial cells (EC). Aim of the present study was to elucidate the renal ...distribution of the components of this complex under control conditions and in a Thy1 nephritis model of proteinuric renal disease. Thy1 nephritis was induced by intravenous injection of OX7 anti‐Thy1 antibody (1mg/kg body weight). Distribution of Plg, tPA and ANXA2 was studied by immunofluorescence in controls and after 5 or 15 days of OX7 injection. Immunoreactive structures were further characterized by double‐labeling immunofluorescence using antibodies against rat endothelial cell antigen for EC, Na(+),K(+),2Cl(−) cotransporter for thick ascending limbs (TAL), aquaporin‐1 for thin descending limbs (tDL) and aquaporin‐2 for collecting ducts (CD). As expected, all three proteins were identified in EC of controls and Thy1 animals. In addition we found overlapping signal for tPA, Plg and ANXA2 in the basolateral and apical membrane of tDL, TAL and CD both, in treated and untreated animals. Furthermore, abundance of tPA and Plg in the apical membrane of TAL and CD was increased in proteinuric animals. In conclusion, our results provide evidence for the presence of a proteolytic complex in the apical membrane of renal epithelia where it may play a protective role in the setting of proteinuric disease.
support: DFG FOR 667
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aim of the present study was to identify Annexin A1 (ANXA1) expressing renal interstitial cells under control conditions and during the course of acute Thy1 nephritis. ANXA1 immunoreactive ...interstitial cells were characterized by double labelling immunofluorescence using antibodies against ANXA1 and rat endothelial cell antigen for endothelial cells, 5′ecto‐nucleotidase for interstitial fibroblasts, Major Histocompatibility Complex II for dendritic cells and CD68 for macrophages. In addition, ANXA1 expression of CD68 positive macrophages was studied during the time course of acute Thy1 nephritis (control, 24h, 5d, 15d). In control rats ANXA1 was detected in all interstitial fibroblasts, and in a subset of macrophages and endothelial cells. Dendritic cells were negative. Thy1 nephritis caused a transient glomerular infiltration of CD68 positive/ANXA1 negative macrophages with peak levels at 24h (610 +/− 126% of controls) and lower levels at the later time points (5d: 395 +/− 26% and 15d: 282 +/− 29% of control; p < .05 for each time point). The number of ANXA1 immunoreactive interstitial macrophages increased to 140 +/− 6% and to 175 +/− 21% of controls on d5 and d15 (p < .05). We have thus shown that ANXA1 is produced by numerous renal interstitial cell types of healthy rats and that infiltrating macrophages may be an important source of renal ANXA1 during the resolution phase of renal inflammatory disease.
Work was supported by the German Research Foundation (FOR 667).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Since the mid-1990s EU institutions and EU policy-making outcomes have had a considerably more noticeable bearing on the regulation and subsequent development of sport than in the first four decades ...of European integration. While the developments at European level are relatively well documented, the actual impact of EU law and policy-making on the domestic arena has so far largely escaped thorough academic attention. This essay will give a brief overview of the increased attention that sport has received in EU politics and policy, before embarking on an analysis regarding the result this may have for domestic sport. Our empirical focus is on German football, particularly on three sub-cases: (I) the nationality issue related to the Bosman ruling, (II) the transfer rules resulting from Bosman, and (III) the issue of broadcasting rights. Our (comparative) empirical analysis suggests that domestic level actors can influence the impact of EU level decisions to (quite) some extent. Hence, outcomes depend both on the strength of EU level pressures for domestic change and on domestic level counter-reactions. We argue that the interplay of these levels has led to different outcomes: 'system transformation' (Case I), 'heavy adjustment' (Case II) and 'partial adjustment' (Case III).
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BFBNIB, FSPLJ, NUK, PILJ, SAZU, UL, UM, UPUK
Background and Aim: The diagnostic and therapeutic relevance of CARD15 genotyping in Crohn's disease (CD) for daily clinical practice has not been investigated so far. We therefore analyzed whether ...CARD15 variants are independent predictive factors for small bowel stenosis in CD evaluated by magnetic resonance enteroclysis (MRE). On the basis of these findings, the potential implications for patient management were investigated. Methods: Eighty CD patients with clinical symptoms suggestive of small bowel stenosis were included. All patients were genotyped for the CARD15 variants c.2104C > T (p.R702W), c.2722G > C (p.G908R), and c.3019_3020insC (p.Leu1007fsX1008) and examined by MRE of the small bowel. Results: CARD15 variants were found in 40 (50%) patients. MRE identified 31 (38%) patients with small bowel stenoses. Twenty‐five of the 40 (62%) patients with at least one CARD15 variant were diagnosed of intestinal stenosis by MRE (odds ratio OR = 9.44; confidence interval CI 3.21–27.77; P = 0.00028, Bonferroni corrected). Particularly, the presence of the 1007fs variant was associated with an increased risk of an intestinal stenosis (OR = 12.00, CI 3.47–41.54, P = 0.00042, Bonferroni corrected). Twenty‐one of 31 (68%) patients with stenoses required surgical intervention, with 13 of these 21 (62%) patients carrying the 1007fs variant. Conclusion: In the largest prospective study analyzing the diagnostic value of CARD15 variants in CD patients performed so far, we identified the 1007fs variant as strong predictor for intestinal stenoses with need for surgery in CD patients. Genotyping could therefore be an important diagnostic tool in clinical practice for identifying high‐risk patients with specific diagnostic and therapeutic needs. Moreover, MRE is an excellent technique for diagnosing small bowel stenoses.
(ProQuest: ... denotes formulae and/or non-USASCII text omitted; see image) The energy flow created in pp collisions at ... is studied within the pseudorapidity range 1.9<eta<4.9 with data collected ...by the LHCb experiment. The measurements are performed for inclusive minimum-bias interactions, hard scattering processes and events with an enhanced or suppressed diffractive contribution. The results are compared to predictions given by Pythia-based and cosmic-ray event generators, which provide different models of soft hadronic interactions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The angular distributions and the partial branching fraction of the decay B0→K*0μ+μ− are studied by using an integrated luminosity of 0.37 fb−1 of data collected with the LHCb detector. The ...forward-backward asymmetry of the muons, AFB, the fraction of longitudinal polarization, FL, and the partial branching fraction dB/dq2 are determined as a function of the dimuon invariant mass. The measurements are in good agreement with the standard model predictions and are the most precise to date. In the dimuon invariant mass squared range 1.00-6.00 GeV2/c4, the results are AFB=−0.06+0.13−0.14±0.04, FL=0.55±0.10±0.03, and dB/dq2=(0.42±0.06±0.03)×10−7 c4/GeV2. In each case, the first error is statistical and the second systematic.
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