5,759 research outputs found
Spin 3 cubic vertices in a frame-like formalism
Till now most of the results on interaction vertices for massless higher spin
fields were obtained in a metric-like formalism using completely symmetric
(spin-)tensors. In this, the Lagrangians turn out to be very complicated and
the main reason is that the higher the spin one want to consider the more
derivatives one has to introduce. In this paper we show that such
investigations can be greatly simplified if one works in a frame-like
formalism. As an illustration we consider massless spin 3 particle and
reconstruct a number of vertices describing its interactions with lower spin 2,
1 and 0 ones. In all cases considered we give explicit expressions for the
Lagrangians and gauge transformations and check that the algebra of gauge
transformations is indeed closed.Comment: 17 pades, no figure
Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis
The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway represents a promising therapeutic target to prevent fibrosis. We have tested the effects of new pharmacological inhibitors of MRTF/SRF signalling in a preclinical model of fibrosis. CCG-222740, a novel MRTF/SRF inhibitor, markedly decreased SRF reporter gene activity and showed a greater inhibitory effect on MRTF/SRF target genes than the previously described MRTF-A inhibitor CCG-203971. CCG-222740 was also five times more potent, with an IC50 of 5 μM, in a fibroblast-mediated collagen contraction assay, was less cytotoxic, and a more potent inhibitor of alpha-smooth muscle actin protein expression than CCG-203971. Local delivery of CCG-222740 and CCG-203971 in a validated and clinically relevant rabbit model of scar tissue formation after glaucoma filtration surgery increased the long-term success of the surgery by 67% (P < 0.0005) and 33% (P < 0.01), respectively, and significantly decreased fibrosis and scarring histologically. Unlike mitomycin-C, neither CCG-222740 nor CCG-203971 caused any detectable epithelial toxicity or systemic side effects with very low drug levels measured in the aqueous, vitreous, and serum. We conclude that inhibitors of MRTF/SRF-regulated gene transcription such as CCG-222740, potentially represent a new therapeutic strategy to prevent scar tissue formation in the eye and other tissues
Siglecg Limits the Size of B1a B Cell Lineage by Down-Regulating NFκB Activation
BACKGROUND: B1 B cells are believed to be a unique lineage with a distinct developmental pathway, function and activation requirement. How this lineage is genetically determined remained largely obscure. METHODS AND PRINCIPAL FINDINGS: Using the Siglecg-deficient mice with a knockin of green-fluorescent protein encoding sequence, we show here that, although the Siglecg gene is broadly expressed at high levels in all stages and/or lineages of B cells tested and at lower levels in other lineages, its deletion selectively expanded the B1a B cell lineages, including the frequency of the B1 cell progenitor in the bone marrow and the number of B1a cells in the peritoneal cavity, by postnatal expansion. The expansion of B1a B cells in the peritoneal correlated with enhanced activation of NFkappaB and was ablated by an IKK inhibitor. CONCLUSION AND SIGNIFICANCE: Our data revealed a critical role for Siglec G-NFkappaB pathway in regulating B1a B cell lineage. These data lead to a novel model of B1a lineage development that explains a large array of genetic data in this field
Remote and Selective Control of Astrocytes by Magnetomechanical Stimulation
Astrocytes play crucial and diverse roles in brain health and disease. The ability to selectively control astrocytes provides a valuable tool for understanding their function and has the therapeutic potential to correct dysfunction. Existing technologies such as optogenetics and chemogenetics require the introduction of foreign proteins, which adds a layer of complication and hinders their clinical translation. A novel technique, magnetomechanical stimulation (MMS), that enables remote and selective control of astrocytes without genetic modification is described here. MMS exploits the mechanosensitivity of astrocytes and triggers mechanogated Ca2+ and adenosine triphosphate (ATP) signaling by applying a magnetic field to antibody-functionalized magnetic particles that are targeted to astrocytes. Using purpose-built magnetic devices, the mechanosensory threshold of astrocytes is determined, a sub-micrometer particle for effective MMS is identified, the in vivo fate of the particles is established, and cardiovascular responses are induced in rats after particles are delivered to specific brainstem astrocytes. By eliminating the need for device implantation and genetic modification, MMS is a method for controlling astroglial activity with an improved prospect for clinical application than existing technologies
Simpson's Paradox, Lord's Paradox, and Suppression Effects are the same phenomenon – the reversal paradox
This article discusses three statistical paradoxes that pervade epidemiological research: Simpson's paradox, Lord's paradox, and suppression. These paradoxes have important implications for the interpretation of evidence from observational studies. This article uses hypothetical scenarios to illustrate how the three paradoxes are different manifestations of one phenomenon – the reversal paradox – depending on whether the outcome and explanatory variables are categorical, continuous or a combination of both; this renders the issues and remedies for any one to be similar for all three. Although the three statistical paradoxes occur in different types of variables, they share the same characteristic: the association between two variables can be reversed, diminished, or enhanced when another variable is statistically controlled for. Understanding the concepts and theory behind these paradoxes provides insights into some controversial or contradictory research findings. These paradoxes show that prior knowledge and underlying causal theory play an important role in the statistical modelling of epidemiological data, where incorrect use of statistical models might produce consistent, replicable, yet erroneous results
Sleep quality in middle-aged and elderly Chinese: distribution, associated factors and associations with cardio-metabolic risk factors
Background
Poor sleep quality has been associated with increased risk of heart disease, diabetes and mortality. However, limited information exists on the distribution and determinants of sleep quality and its associations with cardio-metabolic risk factors in Chinese populations. We aimed to evaluate this in the current study.
Methods
A cross-sectional survey conducted in 2005 of 1,458 men and 1,831 women aged 50–70 years from urban and rural areas of Beijing and Shanghai. Using a questionnaire, sleep quality was measured in levels of well, common and poor. Comprehensive measures of socio-demographical and health factors and biomarkers of cardio-metabolic disease were recorded. These were evaluated in association with sleep quality using logistic regression models.
Results
Half of the population reported good sleep quality. After adjusting for potential confounders, women and Beijing residents had almost half the probability to report good sleep quality. Good physical and mental health (good levels of self-rated health (OR 2.48; 95%CI 2.08 to 2.96) and no depression (OR 4.05; 95%CI 3.12 to 5.26)) related to an increased chance of reporting good sleep quality, whereas short sleep duration (<7 hrs OR 0.10; 95%CI 0.07 to 0.14)) decreased it substantially. There were significant associations between levels of sleep quality and concentrations of plasma insulin, total and LDL cholesterol, and index of insulin resistance.
Conclusion
Levels of good sleep quality in middle-age and elderly Chinese were low. Gender, geographical location, self-rated health, depression and sleep quantity were major factors associated with sleep quality. Prospective studies are required to distil the factors that determine sleep quality and the effects that sleep patterns exert on cardio-metabolic health
Benchmark performance of low-cost Sb2Se3 photocathodes for unassisted solar overall water splitting
Determining cost-effective semiconductors exhibiting desirable properties for commercial photoelectrochemical water splitting remains a challenge. Herein, we report a Sb2Se3 semiconductor that satisfies most requirements for an ideal high-performance photoelectrode, including a small band gap and favourable cost, optoelectronic properties, processability, and photocorrosion stability. Strong anisotropy, a major issue for Sb2Se3, is resolved by suppressing growth kinetics via close space sublimation to obtain high-quality compact thin films with favourable crystallographic orientation. The Sb2Se3 photocathode exhibits a high photocurrent density of almost 30mAcm(-2) at 0V against the reversible hydrogen electrode, the highest value so far. We demonstrate unassisted solar overall water splitting by combining the optimised Sb2Se3 photocathode with a BiVO4 photoanode, achieving a solar-to-hydrogen efficiency of 1.5% with stability over 10h under simulated 1 sun conditions employing a broad range of solar fluxes. Low-cost Sb2Se3 can thus be an attractive breakthrough material for commercial solar fuel production. While photoelectrochemical water splitting offers an integrated means to convert sunlight to a renewable fuel, cost-effective light-absorbers are rare. Here, authors report Sb2Se3 photocathodes for high-performance photoelectrochemical water splitting devices
Phonon-assisted radiofrequency absorption by gold nanoparticles resulting in hyperthermia
It is suggested that in gold nanoparticles (GNPs) of about 5 nm sizes used in
the radiofrequency (RF) hyperthermia, an absorption of the RF photon by the
Fermi electron occurs with involvement of the longitudinal acoustic vibrational
mode (LAVM), the dominating one in the distribution of vibrational density of
states (VDOS). This physical mechanism helps to explain two observed phenomena:
the size dependence of the heating rate (HR) in GNPs and reduced heat
production in aggregated GNPs. The argumentation proceeds within the
one-electron approximation, taking into account the discretenesses of energies
and momenta of both electrons and LAVMs. The heating of GNPs is thought to
consist of two consecutive processes: first, the Fermi electron absorbs
simultaneously the RF photon and the LAVM available in the GNP; hereafter the
excited electron gets relaxed within the GNP's boundary, exciting a LAVM with
the energy higher than that of the previously absorbed LAVM. GNPs containing
the Ta and/or Fe impurities are proposed for the RF hyperthermia as promising
heaters with enhanced HRs, and GNPs with rare-earth impurity atoms are also
brought into consideration. It is shown why the maximum HR values should be
expected in GNPs with about 5-7 nm size.Comment: proceedings at the NATO Advanced Research workshop FANEM-2015 (Minsk,
May 25-27, 2015). To be published in the final form in: "Fundamental and
Applied NanoElectroMagnetics" (Springer Science + Business Media B.V.
DNA resection in eukaryotes: deciding how to fix the break
DNA double-strand breaks are repaired by different mechanisms, including homologous
recombination and nonhomologous end-joining. DNA-end resection, the first step in
recombination, is a key step that contributes to the choice of DSB repair. Resection, an
evolutionarily conserved process that generates single-stranded DNA, is linked to checkpoint
activation and is critical for survival. Failure to regulate and execute this process results in
defective recombination and can contribute to human disease. Here, I review recent findings on
the mechanisms of resection in eukaryotes, from yeast to vertebrates, provide insights into the
regulatory strategies that control it, and highlight the consequences of both its impairment and its
deregulation
Revisiting Date and Party Hubs: Novel Approaches to Role Assignment in Protein Interaction Networks
The idea of 'date' and 'party' hubs has been influential in the study of
protein-protein interaction networks. Date hubs display low co-expression with
their partners, whilst party hubs have high co-expression. It was proposed that
party hubs are local coordinators whereas date hubs are global connectors. Here
we show that the reported importance of date hubs to network connectivity can
in fact be attributed to a tiny subset of them. Crucially, these few, extremely
central, hubs do not display particularly low expression correlation,
undermining the idea of a link between this quantity and hub function. The
date/party distinction was originally motivated by an approximately bimodal
distribution of hub co-expression; we show that this feature is not always
robust to methodological changes. Additionally, topological properties of hubs
do not in general correlate with co-expression. Thus, we suggest that a
date/party dichotomy is not meaningful and it might be more useful to conceive
of roles for protein-protein interactions rather than individual proteins. We
find significant correlations between interaction centrality and the functional
similarity of the interacting proteins.Comment: 27 pages, 5 main figures, 4 supplementary figure
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