52 research outputs found

    Proton emission from the deformed odd-odd nuclei near drip line

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    Proton emission from odd-odd nuclei is studied within the two quasiparticle plus rotor model which includes the non-adiabatic effects and the residual interaction between valence proton and neutron. Justification of the formalism is discussed through corroboration of our results with the experimental spectrum of 180Ta. Exact calculations are performed to get the proton emission halflives. Our results for the proton emitter 130Eu leads to the assignment of spin and parity JĎ€ = 1+ for the ground state. The role of Coriolis and residual neutron-proton interactions on the proton emission halflives and their interplay are also discussed

    Statistical techniques to construct assays for identifying likely responders to a treatment under evaluation from cell line genomic data

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    <p>Abstract</p> <p>Background</p> <p>Developing the right drugs for the right patients has become a mantra of drug development. In practice, it is very difficult to identify subsets of patients who will respond to a drug under evaluation. Most of the time, no single diagnostic will be available, and more complex decision rules will be required to define a sensitive population, using, for instance, mRNA expression, protein expression or DNA copy number. Moreover, diagnostic development will often begin with in-vitro cell-line data and a high-dimensional exploratory platform, only later to be transferred to a diagnostic assay for use with patient samples. In this manuscript, we present a novel approach to developing robust genomic predictors that are not only capable of generalizing from in-vitro to patient, but are also amenable to clinically validated assays such as qRT-PCR.</p> <p>Methods</p> <p>Using our approach, we constructed a predictor of sensitivity to dacetuzumab, an investigational drug for CD40-expressing malignancies such as lymphoma using genomic measurements of cell lines treated with dacetuzumab. Additionally, we evaluated several state-of-the-art prediction methods by independently pairing the feature selection and classification components of the predictor. In this way, we constructed several predictors that we validated on an independent DLBCL patient dataset. Similar analyses were performed on genomic measurements of breast cancer cell lines and patients to construct a predictor of estrogen receptor (ER) status.</p> <p>Results</p> <p>The best dacetuzumab sensitivity predictors involved ten or fewer genes and accurately classified lymphoma patients by their survival and known prognostic subtypes. The best ER status classifiers involved one or two genes and led to accurate ER status predictions more than 85% of the time. The novel method we proposed performed as well or better than other methods evaluated.</p> <p>Conclusions</p> <p>We demonstrated the feasibility of combining feature selection techniques with classification methods to develop assays using cell line genomic measurements that performed well in patient data. In both case studies, we constructed parsimonious models that generalized well from cell lines to patients.</p

    Non-adiabatic description of proton emission from the odd-odd nucleus 130Eu

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    We discuss the non-adiabatic quasiparticle approach for calculating the rotational spectra and decay width of odd-odd proton emitters. The Coriolis effects are incorporated in both the parent and daughter wave functions. Results for the two probable ground states (1+ and 2+) of the proton emitter 130Eu are discussed. With our calculations, we confirm the proton emitting state to be the IĎ€ = 1+ state, irrespective of the strength of the Coriolis interaction. This study provides us with an opportunity to look into the details of wave functions of deformed odd-odd nuclei to which the proton emission halflives are quite sensitive

    Myeloid-specific GPCR kinase-2 negatively regulates NF-ÎşB1p105-ERK pathway and limits endotoxemic shock in mice.

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    G-protein coupled receptor kinase 2 (GRK2) is a member of a kinase family originally discovered for its role in the phosphorylation and desensitization of G-protein coupled receptors. It is expressed in high levels in myeloid cells and its levels are altered in many inflammatory disorders including sepsis. To address the physiological role of myeloid cell-specific GRK2 in inflammation, we generated mice bearing GRK2 deletion in myeloid cells (GRK2(Δmye)). GRK2(Δmye) mice exhibited exaggerated inflammatory cytokine/chemokine production, and organ injury in response to lipopolysaccharide (LPS, a TLR4 ligand) when compared to wild type littermates (GRK2(fl/fl)). Consistent with this, peritoneal macrophages from GRK2(Δmye) mice showed enhanced inflammatory cytokine levels when stimulated with LPS. Our results further identify TLR4-induced NFκB1p105-ERK pathway to be selectively regulated by GRK2. LPS-induced activation of NFκB1p105-MEK-ERK pathway is significantly enhanced in the GRK2(Δmye) macrophages compared to GRK2(fl/fl) cells and importantly, inhibition of the p105 and ERK pathways in the GRK2(Δmye) macrophages, limits the enhanced production of LPS-induced cytokines/chemokines. Taken together, our studies reveal previously undescribed negative regulatory role for GRK2 in TLR4-induced p105-ERK pathway as well as in the consequent inflammatory cytokine/chemokine production and endotoxemia in mice
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