185 research outputs found
Analysis of Accelerometer Data from a Woven Inflatable Creep Burst Test
Accelerometers were used to montor an inflatable test article during a creep test to failure. The test article experienced impulse events that were classified based on the response of the sensors and their time-dependent manifestation. These impulse events required specialized techniques to process the structural dynamics data. However, certain phenomena were defined as worthy of additional study. An assessment of one phenomena (a frequency near 1000Hz) showed a time dependent frequency and an amplitude that increased significantly near the end of the test. Hence, these observations are expected to drive future understanding of and utility in inflatable space structures
Silmitasertib (CX-4945), a Clinically Used CK2-Kinase Inhibitor with Additional Effects on GSK3β and DYRK1A Kinases: A Structural Perspective
A clinical casein kinase 2 inhibitor, CX-4945 (silmitasertib), shows significant affinity toward the DYRK1A and GSK3β kinases, involved in down syndrome phenotypes, Alzheimer’s disease, circadian clock regulation, and diabetes. This off-target activity offers an opportunity for studying the effect of the DYRK1A/GSK3β kinase system in disease biology and possible line extension. Motivated by the dual inhibition of these kinases, we solved and analyzed the crystal structures of DYRK1A and GSK3β with CX-4945. We built a quantum-chemistry-based model to rationalize the compound affinity for CK2α, DYRK1A, and GSK3β kinases. Our calculations identified a key element for CK2α’s subnanomolar affinity to CX-4945. The methodology is expandable to other kinase selectivity modeling. We show that the inhibitor limits DYRK1A- and GSK3β-mediated cyclin D1 phosphorylation and reduces kinase-mediated NFAT signaling in the cell. Given the CX-4945’s clinical and pharmacological profile, this inhibitory activity makes it an interesting candidate with potential for application in additional disease areas
Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials
BACKGROUND:
Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo.
METHODS:
We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated.
RESULTS:
Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth.
CONCLUSION:
It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations
Remarkable convergent evolution in specialized parasitic Thecostraca (Crustacea)
<p>Abstract</p> <p>Background</p> <p>The Thecostraca are arguably the most morphologically and biologically variable group within the Crustacea, including both suspension feeders (Cirripedia: Thoracica and Acrothoracica) and parasitic forms (Cirripedia: Rhizocephala, Ascothoracida and Facetotecta). Similarities between the metamorphosis found in the Facetotecta and Rhizocephala suggests a common evolutionary origin, but until now no comprehensive study has looked at the basic evolution of these thecostracan groups.</p> <p>Results</p> <p>To this end, we collected DNA sequences from three nuclear genes [18S rRNA (2,305), 28S rRNA (2,402), Histone H3 (328)] and 41 larval characters in seven facetotectans, five ascothoracidans, three acrothoracicans, 25 rhizocephalans and 39 thoracicans (ingroup) and 12 Malacostraca and 10 Copepoda (outgroup). Maximum parsimony, maximum likelihood and Bayesian analyses showed the Facetotecta, Ascothoracida and Cirripedia each as monophyletic. The better resolved and highly supported DNA maximum likelihood and morphological-DNA Bayesian analysis trees depicted the main phylogenetic relationships within the Thecostraca as (Facetotecta, (Ascothoracida, (Acrothoracica, (Rhizocephala, Thoracica)))).</p> <p>Conclusion</p> <p>Our analyses indicate a convergent evolution of the very similar and highly reduced slug-shaped stages found during metamorphosis of both the Rhizocephala and the Facetotecta. This provides a remarkable case of convergent evolution and implies that the advanced endoparasitic mode of life known from the Rhizocephala and strongly indicated for the Facetotecta had no common origin. Future analyses are needed to determine whether the most recent common ancestor of the Thecostraca was free-living or some primitive form of ectoparasite.</p
New records of Monstrilloida Sars, 1901 (Crustacea: Copepoda) from Rio Grande do Norte (northeastern coast of Brazil)
Search for B+ -> l+ nu gamma decays with hadronic tagging using the full Belle data sample
We search for the decay B+ -> l+ nu gamma with l+ = e+ or mu+ using the full
Belle data set of 772 x 10^6 BBbar pairs, collected at the Y(4S) resonance with
the Belle detector at the KEKB asymmetric-energy e+e- collider. We reconstruct
one B meson in a hadronic decay mode and search for the B+ -> l+ nu gamma decay
in the remainder of the event. We observe no significant signal within the
phase space of E_gamma^sig > 1 GeV and obtain upper limits of BR(B+ -> e+ nu
gamma) mu+ nu gamma) l+ nu
gamma) < 3.5 x 10^-6 at 90 % credibility level.Comment: Submitted to Phys. Rev.
Search for decays with semileptonic tagging at Belle
We present the results of a search for the rare decays , where stands for and . The results are
obtained with pairs collected with the Belle
detector at the KEKB collider. We reconstruct one meson in a
semileptonic decay and require a single meson but nothing else on the
signal side. We observe no significant signal and set upper limits on the
branching fractions. The limits set on the , , , ,
, and channels
are the world's most stringent.Comment: Submitted to PR
First Observation of Doubly Cabibbo-Suppressed Decay of a Charmed Baryon:
We report the first observation of the decay using a 980 data sample collected by the
Belle detector at the KEKB asymmetric-energy collider. This is the
first doubly Cabibbo-suppressed decay of a charmed baryon to be observed. We
measure the branching ratio of this decay with respect to its Cabibbo-favored
counterpart to be , where the uncertainties are
statistical and systematic, respectively.Comment: 6 pages, 3 figure
Measurement of the branching ratio of relative to decays with hadronic tagging at Belle
We report a measurement of the branching fraction ratios R(D(*)) of Bbar ->
D(*) tau- nubar_tau relative to Bbar -> D()* l- nubar_l (where l = e or mu)
using the full Belle data sample of 772 x 10^6 BBbar pairs collected at the
Y(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e-
collider. The measured values are R(D)= 0.375 +- 0.064(stat.) +- 0.026(syst.)
and R(D*) = 0.293 +- 0.038(stat.) +- 0.015(syst.). The analysis uses hadronic
reconstruction of the tag-side B meson and purely leptonic tau decays. The
results are consistent with earlier measurements and do not show a significant
deviation from the standard model prediction.Comment: Accepted for publication in Phys.Rev.
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