A method to determine the evolution history of the mean neutral hydrogen fraction

The light-cone (LC) effect imprints the cosmological evolution of the redshifted 21-cm signal Tb (n^,ν) along the frequency axis which is the line of sight (LoS) direction of an observer. The effect is particularly pronounced during the Epoch of Reionization (EoR) when the mean hydrogen neutral fraction x HI (ν) falls rapidly as the universe evolves. The multi-frequency angular power spectrum (MAPS) Cℓ(ν1,ν2) quantifies the entire second-order statistics of Tb (n^,ν) considering both the systematic variation along ν due to the cosmological evolution and also the statistically homogeneous and isotropic fluctuations along all the three spatial directions encoded in n^ and ν. Here we propose a simple model where the systematic frequency (ν1 ,ν2) dependence of C ℓ(ν1,ν2) arises entirely due to the evolution of x ¯ HI (ν). This provides a new method to observationally determine the reionization history. Considering a LC simulation of the EoR 21-cm signal, we use the diagonal elements ν 1 =ν2 of Cℓ(ν1,ν2) to validate our model. We demonstrate that it is possible to recover the reionization history across the entire observational bandwidth provided we have the value x ¯ HI at a single frequency as an external input

Glial tumorigenesis: molecular alterations and identification of targets

This article does not have an abstract

Hetero-structure CdS-CuFe2O4 as an efficient visible light active photocatalyst for photoelectrochemical reduction of CO2 to methanol

In the present paper, hetero-structured CdS–CuFe2O4 nanocomposite was synthesized by a facial method to convert CO2 to methanol in the photoelectrochemical (PEC) system. The synthesized catalysts were characterised by XRD, Raman spectroscopy, TEM, FESEM, EDX, XPS, UV–vis and PL spectroscopy. The CdS–CuFe2O4 photocatalyst showed ~6 times higher photocurrent compared to the CuFe2O4 at −0.35 V vs. NHE of bias potential under CO2 environment as revealed by chronoamperometry results. Incident photon to current efficiency (IPCE) for CuFe2O4 and CdS–CuFe2O4 at 470 nm were found as 7.28 and 12.09%, respectively which clearly indicates the proficiency of CdS–CuFe2O4 heterojunction to absorb the visible light resulting in e−/h+ generation and the charge transfer during PEC CO2 reduction. Products in aqueous and gas phases were analysed which confirmed the selective production of methanol with trace amounts of H2 and CO. The CdS–CuFe2O4 catalyst demonstrated 72% and 16.9% of Faradaic and quantum efficiencies, respectively in terms of methanol production where a methanol yield of 23.80 μmole/Lcm2 was achieved in CO2 saturated aqueous solution of NaHCO3 (0.1 M). Detailed investigation revealed that the conduction band (CB) of the CdS in the heterojunction catalyst could act as a CO2 reduction site by trapping photogenerated electrons from the highly photosensitive CuFe2O4 while the water oxidation could take place at the valance band (VB) of CuFe2O4

Frequent loss of heterozygosity and altered expression of the candidate tumor suppressor gene 'FAT' in human astrocytic tumors

Background: We had earlier used the comparison of RAPD (Random Amplification of Polymorphic DNA) DNA fingerprinting profiles of tumor and corresponding normal DNA to identify genetic alterations in primary human glial tumors. This has the advantage that DNA fingerprinting identifies the genetic alterations in a manner not biased for locus. Methods: In this study we used RAPD-PCR to identify novel genomic alterations in the astrocytic tumors of WHO grade II (Low Grade Diffuse Astrocytoma) and WHO Grade IV (Glioblastoma Multiforme). Loss of heterozygosity (LOH) of the altered region was studied by microsatellite and Single Nucleotide Polymorphism (SNP) markers. Expression study of the gene identified at the altered locus was done by semi-quantitative reverse-transcriptase-PCR (RT-PCR). Results: Bands consistently altered in the RAPD profile of tumor DNA in a significant proportion of tumors were identified. One such 500 bp band, that was absent in the RAPD profile of 33% (4/12) of the grade II astrocytic tumors, was selected for further study. Its sequence corresponded with a region of FAT, a putative tumor suppressor gene initially identified in Drosophila. Fifty percent of a set of 40 tumors, both grade II and IV, were shown to have Loss of Heterozygosity (LOH) at this locus by microsatellite (intragenic) and by SNP markers. Semi-quantitative RT-PCR showed low FAT mRNA levels in a major subset of tumors. Conclusion: These results point to a role of the FAT in astrocytic tumorigenesis and demonstrate the use of RAPD analysis in identifying specific alterations in astrocytic tumors

Geometrothermodynamics in Horava-Lifshitz gravity

We investigate the thermodynamic geometries of the most general static, spherically symmetric, topological black holes of the Ho\v{r}ava--Lifshitz gravity. In particular, we show that a Legendre invariant metric derived in the context of geometrothermodynamics for the equilibrium manifold reproduces correctly the phase transition structure of these black holes. Moreover, the limiting cases in which the mass, the entropy or the Hawking temperature vanish are also accompanied by curvature singularities which indicate the limit of applicability of the thermodynamics and the geometrothermodynamics of black holes. The Einstein limit and the case of a black hole with flat horizon are also investigated.Comment: Preliminary draf

Clonal mutations in primary human glial tumors: evidence in support of the mutator hypothesis

<p>Abstract</p> <p>Background</p> <p>A verifiable consequence of the mutator hypothesis is that even low grade neoplasms would accumulate a large number of mutations that do not influence the tumor phenotype (clonal mutations). In this study, we have attempted to quantify the number of clonal mutations in primary human gliomas of astrocytic cell origin. These alterations were identified in tumor tissue, microscopically confirmed to have over 70% neoplastic cells.</p> <p>Methods</p> <p>Random Amplified Polymorphic DNA (RAPD) analysis was performed using a set of fifteen 10-mer primers of arbitrary but definite sequences in 17 WHO grade II astrocytomas (low grade diffuse astrocytoma or DA) and 16 WHO grade IV astrocytomas (Glioblastoma Multiforme or GBM). The RAPD profile of the tumor tissue was compared with that of the leucocyte DNA of the same patient and alteration(s) scored. A quantitative estimate of the overall genomic changes in these tumors was obtained by 2 different modes of calculation.</p> <p>Results</p> <p>The overall change in the tumors was estimated to be 4.24% in DA and 2.29% in GBM by one method and 11.96% and 6.03% in DA and GBM respectively by the other. The difference between high and lower grade tumors was statistically significant by both methods.</p> <p>Conclusion</p> <p>This study demonstrates the presence of extensive clonal mutations in gliomas, more in lower grade. This is consistent with our earlier work demonstrating that technique like RAPD analysis, unbiased for locus, is able to demonstrate more intra-tumor genetic heterogeneity in lower grade gliomas compared to higher grade. The results support the mutator hypothesis proposed by Loeb.</p

MDA-9/Syntenin (SDCBP) Is a Critical Regulator of Chemoresistance, Survival and Stemness in Prostate Cancer Stem Cells

Despite some progress, treating advanced prostate cancer remains a major clinical challenge. Recent studies have shown that prostate cancer can originate from undifferentiated, rare, stem cell-like populations within the heterogeneous tumor mass, which play seminal roles in tumor formation, maintenance of tumor homeostasis and initiation of metastases. These cells possess enhanced propensity toward chemoresistance and may serve as a prognostic factor for prostate cancer recurrence. Despite extensive studies, selective targeted therapies against these stem cell-like populations are limited and more detailed experiments are required to develop novel targeted therapeutics. We now show that MDA-9/Syntenin/SDCBP (MDA-9) is a critical regulator of survival, stemness and chemoresistance in prostate cancer stem cells (PCSCs). MDA-9 regulates the expression of multiple stem-regulatory genes and loss of MDA-9 causes a complete collapse of the stem-regulatory network in PCSCs. Loss of MDA-9 also sensitizes PCSCs to multiple chemotherapeutics with different modes of action, such as docetaxel and trichostatin-A, suggesting that MDA-9 may regulate multiple drug resistance. Mechanistically, MDA-9-mediated multiple drug resistance, stemness and survival are regulated in PCSCs through activation of STAT3. Activated STAT3 regulates chemoresistance in PCSCs through protective autophagy as well as regulation of MDR1 on the surface of the PCSCs. We now demonstrate that MDA-9 is a critical regulator of PCSC survival and stemness via exploiting the inter-connected STAT3 and c-myc pathways

Extensive intra-tumor heterogeneity in primary human glial tumors as a result of locus non-specific genomic alterations

Genomic changes are a hallmark of the neoplastic process. These range from alterations at specific loci and defined karyotypic changes which influence tumor behavior to generalized alterations exemplified by microsatellite instability. Generalized genomic changes within a tumor would be evidence in favor of the mutator hypothesis which postulates a role for such extensive changes during tumorigenesis. In this report, we have used the DNA fingerprinting technique of randomly amplified polymorphic DNA (RAPD) analysis to study genomic alterations within primary human astrocytic tumors (gliomas) in a locus non-specific manner. The RAPD fingerprinting profile of consecutive segments of tumors 2mm across was studied; 17 astrocytic (high-and low-grade) tumors were sectioned end to end. Tissue from 50 consecutive sections, 40μm thick (total 2mm across), was pooled and taken to be a tumor compartment. DNA was subjected to RAPD amplification by 15 random 10-mer primers. A tumor segment was taken to have a DNA fingerprinting pattern different from others in the same specimen when its RAPD profile differed from others by at least one band of one RAPD reaction. All but one of the tumors showed compartments with a unique genetic profile, indicating genomic instability leading to widespread intra-tumor genetic heterogeneity. Eight tumors were also studied for loss of heterozygosity (LOH) of the p53 and D17S379 loci in the different segments as examples of alteration of specific tumor influencing loci. Three showed LOH of p53, which was limited to only one compartment of each tumor. The extensive intra-tumor genetic instability detected in this study is suggestive of the overall high rate of change in the genomes of tumors including those of a lower grade. It is hypothesized that some of these altered clones, which manifest as zones of heterogeneity in a solid tumor, may accumulate changes at loci known to influence tumor behavior, and thus clinical outcome

MDA-7/IL-24 regulates the miRNA processing enzyme DICER through downregulation of MITF

Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a multifunctional cytokine displaying broad-spectrum anticancer activity in vitro or in vivo in preclinical animal cancer models and in a phase 1/2 clinical trial in patients with advanced cancers. mda-7/IL-24 targets specific miRNAs, including miR-221 and miR-320, for down-regulation in a cancer-selective manner. We demonstrate that mda-7/IL-24, administered through a replication incompetent type 5 adenovirus (Ad.mda-7) or with His-MDA-7/IL-24 protein, down-regulates DICER, a critical regulator in miRNA processing. This effect is specific for mature miR-221, as it does not affect Pri-miR-221 expression, and the DICER protein, as no changes occur in other miRNA processing cofactors, including DROSHA, PASHA, or Argonaute. DICER is unchanged by Ad.mda-7/IL-24 in normal immortal prostate cells, whereas Ad.mda-7 down-regulates DICER in multiple cancer cells including glioblastoma multiforme and prostate, breast, lung, and liver carcinoma cells. MDA-7/IL-24 protein down-regulates DICER expression through canonical IL-20/IL-22 receptors. Gain- and loss-of-function studies confirm that overexpression of DICER rescues deregulation of miRNAs by mda-7/IL-24, partially rescuing cancer cells from mda-7/IL-24-mediated cell death. Stable overexpression of DICER in cancer cells impedes Ad.mda-7 or His-MDA-7/IL-24 inhibition of cell growth, colony formation, PARP cleavage, and apoptosis. In addition, stable overexpression of DICER renders cancer cells more resistant to Ad.mda-7 inhibition of primary and secondary tumor growth. MDA-7/IL-24-mediated regulation of DICER is reactive oxygen species-dependent and mediated by melanogenesis-associated transcription factor. Our research uncovers a distinct role of mda-7/IL-24 in the regulation of miRNA biogenesis through alteration of the MITF-DICER pathway