93 research outputs found
Finite Temperature Corrections to Tachyon Mass in Intersecting D-Branes
We continue with the analysis of finite temperature corrections to the
Tachyon mass in intersecting branes which was initiated in arxiv:1403.0389. In
this paper we extend the computation to the case of intersecting D3-branes by
considering a setup of two intersecting branes in flat-space background. A
holographic model dual to BCS superconductor consisting of intersecting
D8-branes in D4-brane background was proposed in arxiv:1104.2843. The
background considered here is a simplified configuration of this dual model. We
compute the one-loop Tachyon amplitude in the Yang-Mills approximation and show
that the result is finite. Analyzing the amplitudes further we numerically
compute the transition temperature at which the Tachyon becomes massless. The
analytic expressions for the one-loop amplitudes obtained here reduce to those
for intersecting D1-branes obtained in arxiv:1403.0389 as well as those for
intersecting D2-branes.Comment: 73 pages, 24 figures, articl
Possible use of self-calibration to reduce systematic uncertainties in determining distance-redshift relation via gravitational radiation from merging binaries
By observing mergers of compact objects, future gravity wave experiments
would measure the luminosity distance to a large number of sources to a high
precision but not their redshifts. Given the directional sensitivity of an
experiment, a fraction of such sources (gold plated -- GP) can be identified
optically as single objects in the direction of the source. We show that if an
approximate distance-redshift relation is known then it is possible to
statistically resolve those sources that have multiple galaxies in the beam. We
study the feasibility of using gold plated sources to iteratively resolve the
unresolved sources, obtain the self-calibrated best possible distance-redshift
relation and provide an analytical expression for the accuracy achievable. We
derive lower limit on the total number of sources that is needed to achieve
this accuracy through self-calibration. We show that this limit depends
exponentially on the beam width and give estimates for various experimental
parameters representative of future gravitational wave experiments DECIGO and
BBO.Comment: 6 pages, 2 figures, accepted for publication in PR
Measles rubella campaign - India’s journey from expanded program on immunization to measles elimination
Infectious diseases have always been a major cause of mortality and morbidity in children under 5 years of age and more so in developing countries like India. Steps toward control of these infectious diseases, especially the vaccine-preventable diseases, have been the priority of Indian Government. Smallpox was eliminated followed by polio and next target being measles. Although the journey has been tough, finally, the results are appreciable considering the large population and limited resources of the country. India has traveled a very long distance from the introduction of vaccination and acquiring country’s vaccine manufacturing to finally eliminating measles
Acute Kidney Injury, Immune Thrombocytopenic Purpura, and the Infection That Binds Them Together: Disseminated Histoplasmosis
Untreated human immunodeficiency virus (HIV) can be complicated by opportunistic infections, including disseminated histoplasmosis (DH). Although endemic to portions of the United States and usually benign, DH can rarely act as an opportunistic infection in immunocompromised patients presenting with uncommon complications such as acute kidney injury and idiopathic thrombocytopenic purpura. We report a rare presentation of DH presenting with acute kidney injury and immune thrombocytopenic purpura in an immunocompromised patient with HIV
Magnetization transfer ratio measures in normal-appearing white matter show periventricular gradient abnormalities in multiple sclerosis
In multiple sclerosis, grey matter pathology occurs mostly next to or near the outer surface of the brain. Using quantitative MRI, Liu et al. reveal that white matter abnormalities are also greatest near the surface of the brain, suggesting common elements in the genesis of grey and white matter patholog
Recurrent RhoGAP gene fusion CLDN18-ARHGAP26 promotes RHOA activation and focal adhesion kinase and YAP-TEAD signalling in diffuse gastric cancer
OBJECTIVE: Genomic studies of gastric cancer have identified highly recurrent genomic alterations impacting RHO signalling, especially in the diffuse gastric cancer (DGC) histological subtype. Among these alterations are interchromosomal translations leading to the fusion of the adhesion protein CLDN18 and RHO regulator ARHGAP26. It remains unclear how these fusion constructs impact the activity of the RHO pathway and what is their broader impact on gastric cancer development. Herein, we developed a model to allow us to study the function of this fusion protein in the pathogenesis of DGC and to identify potential therapeutic targets for DGC tumours with these alterations.
DESIGN: We built a transgenic mouse model with LSL-CLDN18-ARHGAP26 fusion engineered into the Col1A1 locus where its expression can be induced by Cre recombinase. Using organoids generated from this model, we evaluated its oncogenic activity and the biochemical effects of the fusion protein on the RHOA pathway and its downstream cell biological effects in the pathogenesis of DGC.
RESULTS: We demonstrated that induction of CLDN18-ARHGAP26 expression in gastric organoids induced the formation of signet ring cells, characteristic features of DGC and was able to cooperatively transform gastric cells when combined with the loss of the tumour suppressor geneTrp53. CLDN18-ARHGAP26 promotes the activation of RHOA and downstream effector signalling. Molecularly, the fusion promotes activation of the focal adhesion kinase (FAK) and induction of the YAP pathway. A combination of FAK and YAP/TEAD inhibition can significantly block tumour growth.
CONCLUSION: These results indicate that the CLDN18-ARHGAP26 fusion is a gain-of-function DGC oncogene that leads to activation of RHOA and activation of FAK and YAP signalling. These results argue for further evaluation of emerging FAK and YAP-TEAD inhibitors for these deadly cancers
Longer than 2 hours to antibiotics is associated with doubling of mortality in a multinational community-acquired bacterial meningitis cohort
To optimally define the association between time to effective antibiotic therapy and clinical outcomes in adult community-acquired bacterial meningitis. A systematic review of the literature describing the association between time to antibiotics and death or neurological impairment due to adult community-acquired bacterial meningitis was performed. A retrospective cohort, multivariable and propensity-score based analyses were performed using individual patient clinical data from Australian, Danish and United Kingdom studies. Heterogeneity of published observational study designs precluded meta-analysis of aggregate data (I(2) = 90.1%, 95% CI 71.9–98.3%). Individual patient data on 659 subjects were made available for analysis. Multivariable analysis was performed on 180–362 propensity-score matched data. The risk of death (adjusted odds ratio, aOR) associated with treatment after two hours was 2.29 (95% CI 1.28–4.09) and increased substantially thereafter. Similarly, time to antibiotics of greater than three hours was associated with an increase in the occurrence of neurological impairment (aOR 1.79, 95% CI 1.03–3.14). Among patients with community-acquired bacterial meningitis, odds of mortality increase markedly when antibiotics are given later than two hours after presentation to the hospital
Motor network efficiency and disability in multiple sclerosis.
OBJECTIVE: To develop a composite MRI-based measure of motor network integrity, and determine if it explains disability better than conventional MRI measures in patients with multiple sclerosis (MS). METHODS: Tract density imaging and constrained spherical deconvolution tractography were used to identify motor network connections in 22 controls. Fractional anisotropy (FA), magnetization transfer ratio (MTR), and normalized volume were computed in each tract in 71 people with relapse onset MS. Principal component analysis was used to distill the FA, MTR, and tract volume data into a single metric for each tract, which in turn was used to compute a composite measure of motor network efficiency (composite NE) using graph theory. Associations were investigated between the Expanded Disability Status Scale (EDSS) and the following MRI measures: composite motor NE, NE calculated using FA alone, FA averaged in the combined motor network tracts, brain T2 lesion volume, brain parenchymal fraction, normal-appearing white matter MTR, and cervical cord cross-sectional area. RESULTS: In univariable analysis, composite motor NE explained 58% of the variation in EDSS in the whole MS group, more than twice that of the other MRI measures investigated. In a multivariable regression model, only composite NE and disease duration were independently associated with EDSS. CONCLUSIONS: A composite MRI measure of motor NE was able to predict disability substantially better than conventional non-network-based MRI measures
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