Serum microRNA-122 predicts survival in patients with liver cirrhosis

Background: Liver cirrhosis is associated with high morbidity and mortality. MicroRNAs (miRs) circulating in the blood are an emerging new class of biomarkers. In particular, the serum level of the liver-specific miR-122 might be a clinically useful new parameter in patients with acute or chronic liver disease. Aim: Here we investigated if the serum level of miR-122 might be a prognostic parameter in patients with liver cirrhosis. Methods: 107 patients with liver cirrhosis in the test cohort and 143 patients in the validation cohort were prospectively enrolled into the present study. RNA was extracted from the sera obtained at the time of study enrollment and the level of miR-122 was assessed. Serum miR-122 levels were assessed by quantitative reverse-transcription PCR (RT-PCR) and were compared to overall survival time and to different complications of liver cirrhosis. Results: Serum miR-122 levels were reduced in patients with hepatic decompensation in comparison to patients with compensated liver disease. Patients with ascites, spontaneous bacterial peritonitis and hepatorenal syndrome had significantly lower miR-122 levels than patients without these complications. Multivariate Cox regression analysis revealed that the miR-122 serum levels were associated with survival independently from the MELD score, sex and age. Conclusions: Serum miR-122 is a new independent marker for prediction of survival of patients with liver cirrhosis

Grid-based Hybrid 3DMA GNSS and Terrestrial Positioning

The paper discusses the increasing use of hybridized sensor information for GNSS-based localization and navigation, including the use of 3D map-aided GNSS positioning and terrestrial systems based on different geometric measurement principles. However, both GNSS and terrestrial systems are subject to negative impacts from the propagation environment, which can violate the assumptions of conventionally applied parametric state estimators. Furthermore, dynamic parametric state estimation does not account for multi-modalities within the state space leading to an information loss within the prediction step. In addition, the synchronization of non-deterministic multi-rate measurement systems needs to be accounted. In order to address these challenges, the paper proposes the use of a non-parametric filtering method, specifically a 3DMA multi-epoch Grid Filter, for the tight integration of GNSS and terrestrial signals. Specifically, the fusion of GNSS, Ultra-wide Band (UWB) and vehicle motion data is introduced based on a discrete state representation. Algorithmic challenges, including the use of different measurement models and time synchronization, are addressed. In order to evaluate the proposed method, real-world tests were conducted on an urban automotive testbed in both static and dynamic scenarios. We empirically show that we achieve sub-meter accuracy in the static scenario by averaging a positioning error of $0.64$ m, whereas in the dynamic scenario the average positioning error amounts to $1.62$ m. The paper provides a proof-of-concept of the introduced method and shows the feasibility of the inclusion of terrestrial signals in a 3DMA positioning framework in order to further enhance localization in GNSS-degraded environments

Colloidal Gold Labelling of Fibrinogen Receptors in Epinephrine – And ADP–Activated Platelet Suspensions

It has been generally accepted for over twenty years that epinephrine stimulates platelet aggregation without inducing shape change. However, it has been recently reported that discoid platelets are not recruited into ADP-or epinephrine-stimulated aggregates. Previous work in our laboratory has suggested that platelet shape change is necessary for the binding of fibrinogen to its surface receptor, which is a prerequisite for platelet aggregation. These studies seem to indicate that epinephrine-induced platelet aggregation does involve shape change. To investigate this possibility, the extent of shape change and fibrinogen binding in suspensions of epinephrine-and ADP-activated and control platelets was assessed by scanning electron microscopy (SEM). Platelets were incubated with 20 μM epinephrine, 20 μM ADP, or vehicle and labelled with 18 nm gold beads conjugated to fibrinogen or to a monoclonal antibody directed against the glycoprotein IIb/IIIa complex which comprises the fibrinogen receptor. Results indicate that shape change does occur in epinephrine-activated platelets as well as ADP-activated platelets. Although GP IIb/IIIa was shown to be present on both discoid and shape-changed, pseudopodial platelets, a significant degree of fibrinogen binding did not occur earlier than the pseudopodial stage in either activated or control suspensions. Platelet aggregation studies showed that the majority of platelets involved in aggregates had changed shape in both ADP-and epinephrine-treated platelet suspensions. These studies suggest that epinephrine-and ADP-induced platelet aggregation occurs via the exposure of fibrinogen receptors on shape-changed platelets

The endemic gastropod fauna of Lake Titicaca : correlation between molecular evolution and hydrographic history

Lake Titicaca, situated in the Altiplano high plateau, is the only ancient lake in South America. This 2- to 3-My-old (where My is million years) water body has had a complex history that included at least five major hydrological phases during the Pleistocene. It is generally assumed that these physical events helped shape the evolutionary history of the lake´s biota. Herein, we study an endemic species assemblage in Lake Titicaca, composed of members of the microgastropod genus Heleobia, to determine whether the lake has functioned as a reservoir of relic species or the site of local diversification, to evaluate congruence of the regional paleohydrology and the evolutionary history of this assemblage, and to assess whether the geographic distributions of endemic lineages are hierarchical. Our phylogenetic analyses indicate that the Titicaca/Altiplano Heleobia fauna (together with few extralimital taxa) forms a species flock. A molecular clock analysis suggests that the most recent common ancestor (MRCAs) of the Altiplano taxa evolved 0.53 (0.28–0.80) My ago and the MRCAs of the Altiplano taxa and their extralimital sister group 0.92 (0.46–1.52) My ago. The endemic species of Lake Titicaca are younger than the lake itself, implying primarily intralacustrine speciation. Moreover, the timing of evolutionary branching events and the ages of two precursors of Lake Titicaca, lakes Cabana and Ballivián, is congruent. Although Lake Titicaca appears to have been the principal site of speciation for the regional Heleobia fauna, the contemporary spatial patterns of endemism have been masked by immigration and/or emigration events of local riverine taxa, which we attribute to the unstable hydrographic history of the Altiplano. Thus, a hierarchical distribution of endemism is not evident, but instead there is a single genetic break between two regional clades. We also discuss our findings in relation to studies of other regional biota and suggest that salinity tolerance was the most likely limiting factor in the evolution of Altiplano species flocks

Feedback Gathering from an Industrial Point of View

Feedback communication channels allow end-users to express their needs, which can be considered in software development and evolution. Although feedback gathering and analysis have been identified as an important topic and several researchers have started their investigation, information is scarce on how software companies currently elicit end-user feedback. In this study, we explore the experiences of software companies with respect to feedback gathering. The results of a case study and online survey indicate two sides of the same coin: on the one hand, most software companies are aware of the relevance of end-user feedback for software evolution and provide feedback channels, which allow end-users to communicate their needs and problems. On the other hand, the quantity and quality of the feedback received varies. We conclude that software companies still do not fully exploit the potential of end-user feedback for software development and evolution

Krüppel-like factor 8 (KLF8) is expressed in gliomas of different WHO grades and is essential for tumor cell proliferation.

Krüppel-like factor 8 (KLF8) has only recently been identified to be involved in tumor cell proliferation and invasion of several different tumor entities like renal cell carcinoma, hepatocellular carcinoma and breast cancer. In the present study, we show for the first time the expression of KLF8 in gliomas of different WHO grades and its functional impact on glioma cell proliferation. In order to get information about KLF8-mRNA regulation qPCR was performed and did not reveal any significant difference in samples (n = 10 each) of non-neoplastic brain (NNB), low-grade gliomas (LGG, WHO°II) and glioblastomas (GBM, WHO°IV). Immunohistochemistry of tissue samples (n = 7 LGG, 11 AA and 12 GBM) did not show any significant difference in the fraction of KLF8-immunopositive cells of all analyzed cells in LGG (87%), AA (80%) or GBM (89%). Tissue samples from cerebral breast cancer metastasis, meningiomas but also non-neoplastic brain demonstrated comparable relative cell counts as well. Moreover, there was no correlation between KLF8 expression and the expression pattern of the assumed proliferation marker Ki67, which showed high variability between different tumor grade (9% (LGG), 6% (AA) and 15% (GBM) of Ki67-immunopositive cells). Densitometric analysis of Western blotting revealed that the relative amount of KLF8-protein did also not differ between the highly aggressive and proliferative GBM (1.05) compared to LGG (0.93; p<0.05, studens t-test). As demonstrated for some other non-glial cancer entities, KLF8-knockdown by shRNA in U87-MG cells confirmed its functional relevance, leading to an almost complete loss of tumor cell proliferation. Selective blocking of KLF8 might represent a novel anti-proliferative treatment strategy for malignant gliomas. Yet, its simultaneous expression in non-proliferating tissues could hamper this approach