Miracle-dz/UniFAR-FTUs huggingface dataset:
The Calcium/Calcineurin Pathway Promotes Hemidesmosome Stability through Inhibition of β4 Integrin Phosphorylation*

Background: β4 integrin phosphorylation regulates hemidesmosome disassembly, a process necessary for migration and carcinoma invasion. Results: Inhibition of calcineurin increases β4 phosphorylation, hemidesmosome disassembly, and migration. Activating calcineurin stabilizes hemidesmosomes. Conclusion: The calcium/calcineurin pathway stabilizes hemidesmosomes and controls migration by regulating β4 phosphorylation. Significance: These findings help understanding how cells modulate movement by assembling/disassembling anchorage structures, with interesting implications in calcineurin-inhibitor induced cancer. Cell migration depends on cells being able to create and disassemble adhesive contacts. Hemidesmosomes are multiprotein structures that attach epithelia to basal lamina and disassemble during migration and carcinoma invasion. Phosphorylation of the β4 integrin, a hemidesmosome component, induces disassembly. Although kinases involved in β4 phosphorylation have been identified, little is known about phosphatases countering kinase action. Here we report that calcineurin, a serine-threonine protein phosphatase, regulates β4 phosphorylation. Calcineurin inhibitor cyclosporin A (CsA) and calcineurin-siRNA increase β4 phosphorylation, induce hemidesmosome disassembly, and increase migration in HaCat keratinocytes, suggesting that calcineurin negatively regulates β4 phosphorylation. We found no direct dephosphorylation of β4 by calcineurin or association between β4 and calcineurin, suggesting indirect regulation of β4 phosphorylation. We therefore assessed calcineurin influence on MAPK and PKC, known to phosphorylate β4. CsA increased MAPK activity, whereas MAPK inhibitors reduced CsA-induced β4 phosphorylation, suggesting that calcineurin restricts β4 phosphorylation by MAPK. Calcineurin is activated by calcium. Increased [Ca2+]i reduces β4 phosphorylation and stabilizes hemidesmosomes, effects that are reversed by CsA, indicating that calcineurin mediates calcium effects on β4. However, MAPK activation is increased when [Ca2+]i is increased, suggesting that calcineurin activates an additional mechanism that counteracts MAPK-induced β4 phosphorylation. Interestingly, in some squamous cell carcinoma cells, which have reduced hemidesmosomes and increased β4 phosphorylation, an increase in [Ca2+]i using thapsigargin, bradykinin, or acetylcholine can increase hemidesmosomes and reduce β4 phosphorylation in a calcineurin-dependent manner. These findings have implications in calcineurin-inhibitor induced carcinoma, a complication of immunosuppressive therapy.
An Introduction to a Bayesian Method for Meta-analysis

The Confidence Profile Method is a new Bayesian method that can be used to assess technologies where the available evidence involves a variety of experimental designs, types of outcomes, and effect measures; a variety of biases; combinations of biases and nested biases; uncertainty about biases; an underlying variability in the parameter of interest; indirect evidence; and technology families. The result of an analysis with the Confidence Profile Method is a posterior distribution for the parameter of interest, posterior distributions for other parameters, and a covariance matrix for all the parameters in the model. The posterior distributions incorporate all the uncertainty the assessor chooses to describe about any of the parameters used in the analysis. Key words: Confidence Profile Method; bias; Bayesian analysis; meta-analysis. (Med Decis Making 1990;10:15-23)
Domain organization and a protease-sensitive loop in eukaryotic ornithine decarboxylase.

Trypanosoma brucei ornithine decarboxylase was reconstituted by coexpression of two polypeptides corresponding to residues 1-305 and residues 306-425 in Escherichia coli. The two peptides were coexpressed, at wild-type levels, from a single transcriptional unit that was separated by a 15-nucleotide untranslated region containing a ribosome binding site. The fragmented enzyme was purified and analyzed. The N- and C-terminal peptides are tightly associated into a fully active tetramer which has the same molecular weight as the native dimer. The kinetic constants (Km and kcat) measured for the decarboxylation of ornithine are identical to those obtained for the wild-type enzyme. These results suggest that the enzyme is organized into two structural domains, with a domain boundary in the region of amino acid 305. In contrast, the individual N- and C-terminal peptides are expressed primarily as inclusion bodies. Small quantities of soluble N-terminal peptide could be purified. This truncated protein is capable of inhibiting the wild-type enzyme, suggesting that it is folded into a native-like structure. Limited proteolysis with trypsin or chymotrypsin identifies a likely surface loop at amino acids 160-170, present in both the mouse and T. brucei enzyme, which positions one or more functionally important active site residues (e.g., Lys169). Kinetic analysis of a chimeric enzyme composed of T. brucei and mouse ornithine decarboxylase suggests that the substrate carboxylate binding determinant is located between residues 1 and 170.
Cooperative Localization Using Posterior Linearization Belief Propagation

This paper presents the posterior linearization belief propagation (PLBP) algorithm for cooperative localization in wireless sensor networks with nonlinear measurements. PLBP performs two steps iteratively: linearization and belief propagation. At the linearization step, the nonlinear functions are linearized using statistical linear regression with respect to the current beliefs. This SLR is performed in practice by using sigma-points drawn from the beliefs. In the second step, belief propagation is run on the linearized model. We show by numerical simulations how PLBP can outperform other algorithms in the literature.
Hematopoietic Stem Cells in the Mouse Embryonic Yolk Sac

The yolk sac is the first site of hematopoiesis during mammalian development. The yolk sac is also the first site of blood vessel development. Development of the blood islands in the yolk sac is an integrated process in which these two developmental events, hematopoiesis and vasculogenesis, proceed in concert. This review focuses on mouse yolk sac hematopoietic stem cells (YS‐HSC), describing their differentiation in vitro and in vivo. YS‐HSC go through a progressive series of changes prior to the initiation of lineage‐specific differentiation. Experiments tracing their origins from postulated hemangioblasts, and the subsequent interaction between these stem cells and yolk sac endothelial cells are described. Differences between the extraembryonic YS‐HSC and HSC found later within the embryo, perinatally or in adults, are described. YS‐HSC have greater reproductive capability than HSC obtained from fetal liver, umbilical cord blood or adult bone marrow; they do not yet express major histocompatibility complex‐associated antigens and they are able to reconstitute adult immunocompromised animals even when introduced in small numbers (<100 cells/mouse). With recent results demonstrating the feasibility of expanding YS‐HSC in vitro as well as of introducing new genes into these cells by transfection, the YS‐HSC shows promise both as a means of achieving long‐term restitution of hematopoiesis across histocompatibility barriers and as a self‐renewing vehicle for gene transfer.
A wide‐range survey of cross‐species microsatellite amplification in birds

The possibility to perform cross‐species microsatellite amplification in birds was surveyed by analysing sets of primers developed from the swallow and the pied flycatcher genomes on a panel of 48 different bird species. In total, 162 cases (species/marker combinations) of heterologous amplification were recorded. Ten amplification products were sequenced and all were found to be true homologues of the original loci. There was a significant and negative relationship between microsatellite performance and evolutionary distance between the original species and the tested species. As a rough indicator of expected cross‐species microsatellite performance we estimate that 50% of markers will reveal polymorphism in a species with a DNA‐DNA hybridization δTmH value of 5 separating it from the original species. This corresponds to a divergence time of = 11 million years before present for passerine birds. The established relationship between performance and evolutionary distance agrees very well with data obtained from some mammalian species. The proportion of polymorphic loci among those markers that amplified decreased with increasing genetic distance, suggesting that few long repeats are preserved during evolution. One of the swallow markers, HrU2, amplified a specific product in all species analysed and will thus allow access to nuclear sequence data over a broad range of species. The only predictor of cross‐species performance was the amount of non‐specific amplification seen in the original species. An analysis of 10 species from within the family Hirundinidae with the swallow primers consistently revealed extensive polymorphism with average probabilities of identical genotypes ranging from 6 times 10‐4 to 6 times 10‐7. There were distinct allele frequency differences between the Hirundinidae species and we envisage that microsatellite cross‐species amplification will be a useful tool in phylogeny construction and in species identification.
An RNA Polymerase II Complex Containing All Essential Initiation Factors Binds to the Activation Domain of PAR Leucine Zipper Transcription Factor Thyroid Embryonic Factor

ABSTRACT Transcription initiation of protein-encoding genes involves the assembly of RNA polymerase II and a number of general transcription factors at the promoter. A mammalian RNA polymerase II complex containing all of the components required for promoter-specific transcription initiation can be isolated by immunopurification with a monoclonal antibody directed against the cyclin-dependent kinase CDK7, a subunit of the general transcription factor TFIIH. In vitro transcription by this immunopurified RNA polymerase II complex is effectively stimulated by thyroid embryonic factor (TEF), a basic leucine zipper transcription factor. Thus, the RNA polymerase II complex must also contain components required for activated transcription that interact with the transactivation domain of TEF. This conjecture was verified by affinity selection experiments in which the TEF transcription activation domain was used as a bait. Indeed, an RNA polymerase II complex containing all of the accessory proteins required for transcription initiation can be enriched by its affinity to recombinant proteins containing the TEF transactivation domain. These results are compatible with a mechanism by which TEF can recruit an RNA polymerase II holoenzyme to the promoter in a single step.
Data Fusion Strategies in Advanced Driver Assistance Systems

Data fusion plays a central role in more and more automotive applications, especially for driver assistance systems. On the one hand the process of data fusion combines data and information to estimate or predict states of observed objects. On the other hand data fusion introduces abstraction layers for data description and allows building more flexible and modular systems. The data fusion process can be divided into a low-level processing (tracking and object discrimination) and a high level processing (situation assessment). High level processing becomes more and more the focus of current research as different assistance applications will be combined into one comprehensive assistance system. Different levels/strategies for data fusion can be distinguished: Fusion on raw data level, fusion on feature level and fusion on decision level. All fusion strategies can be found in current driver assistance implementations. The paper gives an overview of the different fusion strategies and shows their application in current driver assistance systems. For low level processing a raw data fusion approach in a stereo video system is described, as an example for feature level fusion the fusion of radar and camera data for tracking is explained. As an example for a high level fusion algorithm an approach for a situation assessment based on multiple sensors is given. The paper describes practical realizations of these examples and points out their potential to further increase traffic safety with reasonably low cost for the overall system.
Effect of stem age on the response of stem diameter variations to plant water status in tomato

Plant water status plays a major role in glasshouse cultivation of tomato (Solanum lycopersicum L.). New climate control technologies alter the glasshouse climate and make it less dependent on solar radiation. However, irrigation strategies are still often based on solar radiation sums. In order to maintain a good plant water status, it is interesting to use plant-based methods such as monitoring sap flow (F) or stem diameter variations (SDV). Though SDV give important information about plant water status, an unambiguous interpretation might be difficult because other factors such as stem age, fruit load and sugar content of the stem also affect SDV. In this study, an analysis of the effect of stem age on the response of SDV to water status was performed by calibration of a mechanistic flow and storage model. This allowed us to determine how parameter values changed across the growing season. Tissue extensibility decreased over the growing season resulting in a lower growth rate potential, whereas daily cycles of shrinking and swelling of the stem became more pronounced towards the end of the growing season. Parameters were then adapted to time-dependent variables and implemented in the model, allowing long term simulation and interpretation of SDV. Sensitivity analysis showed that model predictions were very sensitive to initial sucrose content of the phloem tissue and the parameters related to plastic growth.
Pre-mRNA splicing and human disease.

The precision and complexity of intron removal during pre-mRNA splicing still amazes even 26 years after the discovery that the coding information of metazoan genes is interrupted by introns (Berget et al. 1977; Chow et al. 1977). Adding to this amazement is the recent realization that most human genes express more than one mRNA by alternative splicing, a process by which functionally diverse protein isoforms can be expressed according to different regulatory programs. Given that the vast majority of human genes contain introns and that most pre-mRNAs undergo alternative splicing, it is not surprising that disruption of normal splicing patterns can cause or modify human disease. The purpose of this review is to highlight the different mechanisms by which disruption of pre-mRNA splicing play a role in human disease. Several excellent reviews provide detailed information on splicing and the regulation of splicing (Burge et al. 1999; Hastings and Krainer 2001; Black 2003). The potential role of splicing as a modifier of human disease has also recently been reviewed (NissimRafinia and Kerem 2002).
A high-SNR normal approximation for single-antenna Rayleigh block-fading channels

This paper concerns the maximal achievable rate at which data can be transmitted over a non-coherent, single-antenna, Rayleigh block-fading channel using an error-correcting code of a given blocklength with a block-error probability not exceeding a given value. In particular, a high-SNR normal approximation of the maximal achievable rate is presented that becomes accurate as the signal-to-noise ratio (SNR) and the number of coherence intervals L over which we code tend to infinity. Numerical analyses suggest that the approximation is accurate already at SNR values of 15 dB.
Autonomous Robot Calibration for Hand-Eye Coordination

Autonomous robot calibration is defined as the process of determining a robot's model by using only its internal sen sors. It is shown that autonomous calibration of a manip ulator and stereo camera system is possible. The pro posed autonomous calibration algorithm may obtain the manipulator kinematic parameters, external kinematic camera parameters, and internal camera parameters. To do this, only joint angle readings and camera image plane data are used. A condition for the identifiability of the manipulator/camera parameters is derived. The method is a generalization of a recently developed scheme for self- calibrating a manipulator by forming it into a mobile closed-loop kinematic chain.
Powerful neutron generators based on high current ECR ion sources with gyrotron plasma heating

All material supplied via JYX is protected by copyright and other intellectual property rights, and duplication or sale of all or part of any of the repository collections is not permitted, except that material may be duplicated by you for your research use or educational purposes in electronic or print form. You must obtain permission for any other use. Electronic or print copies may not be offered, whether for sale or otherwise to anyone who is not an authorised user. Powerful neutron generators based on high current ECR ion sources with gyrotron plasma heating Skalyga, V.A. ; Golubev, S.V. ; Izotov, I.V. ; Lapin, R.L. ; Razin, S.V. ; Shaposhnikov, R.A. ; Sidorov, S.V. ; Tarvainen, Olli
Peripheral dose outside applicators in electron beams

The peripheral dose outside the applicators in electron beams was studied using a Varian 21 EX linear accelerator. To measure the peripheral dose profiles and point doses for the applicator, a solid water phantom was used with calibrated Kodak TL films. Peak dose spot was observed in the 4 MeV beam outside the applicator. The peripheral dose peak was very small in the 6 MeV beam and was ignorable at higher energies. Using the 10 × 10 cm2 cutout and applicator, the dose peak for the 4 MeV beam was about 12 cm away from the field central beam axis (CAX) and the peripheral dose profiles did not change with depths measured at 0.2, 0.5 and 1 cm. The peripheral doses and profiles were further measured by varying the angle of obliquity, cutout and applicator size for the 4 MeV beam. The local peak dose was increased with about 3% per degree angle of obliquity, and was about 1% of the prescribed dose (angle of obliquity equals zero) at 1 cm depth in the phantom using the 10 × 10 cm2 cutout and applicator. The peak dose position was also shifted 7 mm towards the CAX when the angle of obliquity was increased from 0 to 15°.
A comparison of Bayesian networks learning algorithms: A case study of webpage layout design

Due to the Internet is become prevalent, webpage is a vital medium, which does duty as a channel in communication process between a website-designer and users. Webpage design consists of many elements such as color, image, layout etc., which may contribute to users perception. The authors have created a knowledge model of webpage layout design by using Bayesian network technique. In order to build appropriate models, several algorithms for learning Bayesian networks have been developed. In this study, four knowledge models of webpage which created based on different structure learning algorithm of Bayesian network were compared for finding the most appropriate algorithm. As a result, it becomes clear that the model created with Tabu search and the K2 algorithm is the most appropriate.
Power flow control in distributed microgrid with wind energy system

In this paper, power flow is controlled in a distributed microgrid. The local loads in the microgrid are supplied from the distributed generator (DG) with wind energy system (WES). In DG, a voltage source inverter (VSI) is operated in a current control mode in order to inject real power and achieve load compensation. The generation of reference currents for voltage source inverter depends upon the available wind power for real power injection and load reactive and harmonic component for load compensation. Simulation studies are performed using PSCAD/EMTDC to validate the proposed power flow control and load compensation in the distributed microgrid.
Further Investigation of the Predictors of Outcome Following First Schizophrenic Episodes

The outcome at two years of patients who were eligible for a study of first schizophrenic episodes was assessed in terms of occupation (n = 237) and in terms of number of days spent as an in-patient from the time of first admission (n = 252), and was related to social, behavioural, mental state and neurological measures during the initial admission. Poor outcome was in general associated with more social withdrawal, inactivity and abnormal social presentation and with more ‘neurological soft signs'. Good occupational outcome in patients with a relatively short pre-treatment duration of illness was associated with the prescription of placebo medication during the follow-up period.
AModel of Postsurgical AdvancedMetastatic Breast Cancer More Accurately Replicates the Clinical Ef fi cacy of Antiangiogenic Drugs

The failure rate of randomized phase III oncology clinical trials is extremely high, even when preceded by encouraging preclinical studies and phase II trial results of the same therapy. Thus, there is considerable effort being made to improve the predictive clinical potential of preclinical models, in addition to improving phase II trial design.With respect to the former, preclinicalmodels have historically relied heavily on treatment of primary spontaneous or transplanted tumors rather than the more common and therapeutically challenging clinical trial circumstance of advancedmetastatic disease. Here, we show that the oral antiangiogenic tyrosine kinase inhibitor (TKI), sunitinib, which failed to meet primary or secondary survival endpoints in 4 separate phase III metastatic breast cancer (MBC) trials, either alone or with chemotherapy, similarly failed to show monotherapy or combination chemotherapy efficacy in a model of postsurgical advanced MBC using a metastatic variant of the MDA-MB-231 triple-negative human breast cancer. In contrast, the drug was effective when used to treat established orthotopic primary tumors. Similar results were obtained with pazopanib monotherapy, another antiangiogenic oral TKI. However, when an antibody targeting the VEGF pathway (DC101) was tested, it showed a trend inmodestly improving the efficacy of paclitaxel therapy, thus resembling to a degree prior phase III clinical results of bevacizumab plus paclitaxel in MBC. Our results suggest the potential value of treating postsurgical advanced metastatic disease as a possible strategy to improve preclinical models for predicting outcomes in patients with metastatic disease. Cancer Res; 73(9); 2743–8. 2013 AACR.
Model-based reinforcement learning with model error and its application

This paper proposes a reinforcement learning (RL) algorithm called model error based Forward planning reinforcement learning (ME-FPRL). In this algorithm, an agent controls the amount of learning by using the model error. This study applies ME-FPRL to the pursuit of a target by a robot camera. The results of this application show that ME-FPRL is more efficient than usual RL and model-based RL.