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Matter falling onto a black hole is trans-relativistic, transonic, and close to the horizon it is sub-Keplerian. Such a flow shows the existence of multiple critical point, shocks etc. Employing relativistic equation of state and realistic composition, it has been shown that the solution strongly depend on the composition of the fluid. Electron-positron fluid is the least relativistic, to the extent that multiple critical points, shocks etc do not form. The most relativistic fluid is the one whose ratio of proton to electron number density is ~ 0.2. Since the solution strongly depend on composition, the emitted radiation should strongly depend on the composition too., Pages 3, 2 figures. Proceedings of the Twelfth Marcel Grossmann Meeting on General Relativity, edited by Thibault Damour, Robert T. Jantzen and Remo Ruffini. ISBN 978-981-4374-51-4. Singapore: World Scientific, 2012, p.982

Microsomal epoxide hydrolase 1 (EPHX1) is involved in the metabolism of environmental and tobacco carcinogens. Tobacco smoking, betel quid chewing, and alcohol consumption are the major known risk factors for esophageal cancer. The present case-control study evaluated the influence of EPHX1 genetic variations on esophageal cancer susceptibility in 142 patients and 185 healthy controls from a high-incidence region of India where tobacco use and alcohol consumption are widespread and the users of these two substances are also betel quid chewers.EPHX1 polymorphic alleles (exon 3, Tyr113His and exon 4, His139Arg) were genotyped by polymerase chain reaction-restriction fragment length polymorphism method and direct sequencing. The results were analyzed using logistic regression to calculate odds ratios (OR) and confidence intervals (CI).Patients with exon 4 genotypes (139His/Arg, 139Arg/Arg) and the 139Arg allele were significantly associated with a risk of esophageal cancer (OR(His139Arg) 1.887, 95% CI = 1.112-3.201, P = 0.019; OR(Arg139Arg) 7.140, 95% CI = 1.276-393.953, P = 0.025 and OR(Arg) 1.83, 95% CI = 1.19-2.82, P = 0.003). The 139His/Arg genotype was a significant risk factor for esophageal cancer in tobacco chewers and betel quid chewers. Patients with the 139Arg/Arg genotype were at significantly higher risk for developing a well-differentiated and moderately-differentiated grade of tumor. In contrast, the 113His/His genotype of exon 3 was a significant protective factor for esophageal cancer in tobacco smokers (OR 0.291, 95% CI = 0.138-0.616, P = 0.001), betel quid chewers (OR 0.434, 95% CI = 0.236-0.797, P = 0.007), and alcohol users.EPHX1 exon 4 139His/Arg, and 139Arg/Arg genotypes were associated with a higher risk of esophageal cancer in a high-risk area of India.

Genomic alterations such as chromosomal amplifications, deletions and loss of heterozygosity play an important role in the pathogenesis and progression of cancer. Environmental risk factors contribute to the development and progression of tumors by facilitating the loss of tumor suppressor genes and amplification of oncogenes. In this current study, Affymetrix 10K single nucleotide polymorphism (SNP) arrays were used to evaluate genomic alterations in 20 pairs of matched germ-line and tumor DNA obtained from patients with esophageal squamous cell carcinoma (ESCC) from high-risk area of India where tobacco, betel quid and alcohol use are widespread. Twenty-two amplified regions and 16 deleted regions identified across chromosomal arms were biologically relevant. The candidate genes located at amplified regions of chromosomes or low-level gain regions such as PLA2G5 (1p36–p34), COL11A1 (1p21), KCNK2 (1q41), S100A3 (1q21), ENAH (1q42.12), RGS1 (1q31), KCNH1 (1q32–q41), INSIG2 (2q14.1), FGF12 (3q28), TRIO (5p15.2), RNASEN (5p15.2), FGF10 (5p13–p12), EDN1(6p24.1–p22.3), SULF1 (8q13.2–13.3), TLR4 (9q32–q33), TNC (9q33), NTRK2 (9q22.1), CD44 (11p13), NCAM1 (11q23.1), TRIM29 (11q22–q23), PAK1 (11q13–q14) and RAB27A (15q15–q21.1), are found to be associated with cellular migration and proliferation, tumor cell metastasis and invasion, anchorage independent growth and inhibition of apoptosis. The candidate genes located at deleted regions of chromosomes, such as FBLN2 (3p25.1), WNT7A (3p25), DLC1 (8p22), LZTS1 (8p22), CDKN2A (9p21), COL4A1 (13q34), CDK8 (13q12) and DCC (18q21.3), are found to be associated with the suppression of tumor. The suggested candidate genes were mostly involved in potential signaling pathways such as focal adhesion (COL4A1), tight junction (CLDN10), MAPK signaling pathway (FGF12) and neuroactive ligand receptor interaction pathway (CCKAR). Expression of FGF12 and COL4A1 was validated by tissue microarray. These unique copy number alteration profiles should be taken into consideration when developing biomarkers for the early detection of ESCC in high-risk areas of India in association with tobacco and betel quid use.

SUMMARY The incidence of esophageal squamous cell carcinoma (ESCC) is very high in the northeast region of India. An earlier study from China and Iran suggested that mutations in BRCA2 gene may play a role in the etiology of familial ESCC. However, the frequency of BRCA2 gene germ line mutations and its contribution to risk of familial aggregation of ESCC in high-risk region of India are not known. In the current study of 317 cases of esophageal cancer, 92 (29%) cases had a family history of esophageal and/or other cancers. Of these 92 patients, 45 (49%) patients had a family history of esophageal cancer. The risk of developing esophageal cancer was higher in cases where family history showed occurrence of cancers in first-degree relatives (odds ratio [OR]: 3.1; confidence interval [CI]: 1.9–5.3) than in second-degree relatives (OR: 1.3; CI: 0.25–3.2). Moreover, the risk of developing esophageal cancer was higher in subjects whose predegree suffered from esophageal cancer (OR: 2.4; CI: 1.1–4.1) than from any other cancers (OR: 1.1; CI: 0.32–3.3). The subjects with family history of cancer were more likely to develop ESCC if they were tobacco chewers (OR: 4.2; CI: 2.1–5.8) and betel quid users (OR: 3.6; CI: 1.8–4.6). Screening for mutations of the BRCA2 gene in the germ line DNA was carried out for 20 familial and 80 nonfamilial ESCC patients. One hundred unrelated healthy controls from the same population were included in this study. Nonsynonymous variants in exon 18 (K2729N) and exon 27 (I3412V) of BRCA2 gene were found in 3 of 20 patients with familial ESCC. No sequence alterations were found in 80 nonfamilial ESCC cases (P= 0.01) and 100 healthy controls (P= 0.0037), suggesting that germ line BRCA2 gene mutation may play a role in familial aggregation of ESCC in high-risk region of India.

Esophageal cancer is a frequently fatal malignancy, and is described in certain regions in Northeast India with an incidence of esophageal squamous cell carcinoma is many fold higher than the rest of the population. The population in Northeast India is at higher risk due to poor nutritional status, consumption of fermented betel quid and other oral tobacco products besides smoking and alcohol intake. Cytokeratins are the major constituents of the esophageal epithelium and may show gain or loss of cytokeratins as the cancer progresses from normal epithelium to invasive phenotype. In the present study we studied the immunohistochemical expression of five cytokeratins (CK4, CK5, CK8, CK14, and CK17) in the normal esophageal epithelium and esophageal squamous cell carcinoma from both the general population and the high-risk population of Assam in Northeast India. The cytokeratin expression profile was similar to other published data in general. Further analysis demonstrated differences in cytokeratin expression between the general and the high-risk tumor samples. CK5 and CK 8 expression altered in the high-risk population. The significance of these differences is unclear, but suggests a connection to the etiological factors.

To identify the genes and molecular functional pathways involved in esophageal cancer, we analyzed the gene expression profile of esophageal tumor tissue from patients having family history of esophageal cancer by cDNA microarray. Three hundred and fifty differentially expressed genes (26 up-regulated and 324 down-regulated) were identified. Genes involved in humoral immune response (PF4), extracellular matrix organization (COL4A4), metabolism of xenobiotics (EPHX1), TGF-beta signaling (SMAD1) and calcium signaling pathways (VDAC1) were down-regulated and genes involved in regulation of actin cytoskeleton (WASL), neuroactive ligand receptor interaction (GRM3), Toll-like receptor (CD14), B-cell receptor (IFITM1) and insulin signaling pathways (FOXO1A) were up-regulated. Validation of differential expression of subset of genes by QRT-PCR and tissue microarray in familial and non-familial cases showed no significant difference in expression of these genes in two groups suggesting familial clustering occurs as result of sharing of common environmental factors. Gene expression profiling of clinical specimens from well characterized populations that have familial clustering of cancer identified molecular mechanism associated with progression of esophageal cancer.

Steady, spherically symmetric, adiabatic accretion and wind flows around non-rotating black holes were studied for fully ionized, multi-component fluids, which are described by a relativistic equation of state (EoS). We showed that the polytropic index depends on the temperature as well as on the composition of fluids, so the composition is important to the solutions of the flows. We demonstrated that fluids with different composition can produce dramatically different solutions, even if they have the same sonic point, or they start with the same specific energy or the same temperature. Then, we pointed that the Coulomb relaxation times can be longer than the dynamical time in the problem considered here, and discussed the implication., Comment: Accepted for publication in ApJ. Pdf can be downloaded from http://canopus.cnu.ac.kr/ryu/cr.pdf

Rotating accretion flow may undergo centrifugal pressure mediated shock transition even in presence of various dissipative processes, such as viscosity and cooling mechanism. The extra thermal gradient force along the vertical direction in the post shock flow drives a part of the accreting matter as bipolar outflows which are believed to be the precursor of relativistic jets. We compute mass loss rates from a viscous accretion disc in presence of synchrotron cooling in terms of the inflow parameters. We show cooling significantly affects the mass outflow rate, to the extent that, jets may be generated from flows with higher viscosity. We discuss that our formalism may be employed to explain observed jet power for a couple of black hole candidates. We also indicate that using our formalism, it is possible to connect the spectral properties of the disc with the rate of mass loss., Comment: 18 pages, 7 figures. Accepted in New Astronomy

To identify alterations in genes and molecular functional pathways in esophageal cancer in a high incidence region of India where there is a widespread use of tobacco and betel quid with fermented areca nuts.Total RNA was isolated from tumor and matched normal tissue of 16 patients with esophageal squamous cell carcinoma. Pooled tumor tissue RNA was labeled with Cy3-dUTP and pooled normal tissue RNA was labeled with Cy5-dUTP by direct labeling method. The labeled probes were hybridized with human 10K cDNA chip and expression profiles were analyzed by Genespring GX V 7.3 (Silicon Genetics).Nine hundred twenty three genes were differentially expressed. Of these, 611 genes were upregulated and 312 genes were downregulated. Using stringent criteria (Por = 0.05 andor = 1.5 fold change), 127 differentially expressed genes (87 upregulated and 40 downregulated) were identified in tumor tissue. On the basis of Gene Ontology, four different molecular functional pathways (MAPK pathway, G-protein coupled receptor family, ion transport activity, and serine or threonine kinase activity) were most significantly upregulated and six different molecular functional pathways (structural constituent of ribosome, endopeptidase inhibitor activity, structural constituent of cytoskeleton, antioxidant activity, acyl group transferase activity, eukaryotic translation elongation factor activity) were most significantly downregulated.Several genes that showed alterations in our study have also been reported from a high incidence area of esophageal cancer in China. This indicates that molecular profiles of esophageal cancer in these two different geographic locations are highly consistent.

Centrifugal pressure of matter spiralling onto black holes, have long been known to produce standing or oscillating shocks. The post-shock disc puffs up in the form of a torus, which intercepts soft photons from the outer Keplerian disc and inverse Comptonizes them to produce hard photons. The post-shock region also produces jets. We study the interaction of both hard photons and soft photons, with rotating electron-positron jets. We show that hard photons from the post-shock torus are instrumental in acceleration of jets, while soft photons from the Keplerian disc is a better collimating agent. We also show that if the jets are launched closer to the black hole, relativistic and collimated jets are produced; if they are launched at larger distances both collimation and acceleration are less. We also show that if the shock location is relatively at larger distances from the black hole, collimation is better., Accepted in MNRAS; 39 pages, 13 figures

We self-consistently estimate the outflow rate from the accretion rates of an accretion disk around a black hole in which both the Keplerian and the sub-Keplerian matter flows simultaneously. While Keplerian matter supplies soft-photons, hot sub-Keplerian matter supplies thermal electrons. The temperature of the hot electrons is decided by the degree of inverse Comptonization of the soft photons. If we consider only thermally-driven flows from the centrifugal pressure-supported boundary layer around a black hole, we find that when the thermal electrons are cooled down, either because of the absence of the boundary layer (low compression ratio), or when the surface of the boundary layer is formed very far away, the outflow rate is negligible. For an intermediate size of this boundary layer the outflow rate is maximal. Since the temperature of the thermal electrons also decides the spectral state of a black hole, we predict that the outflow rate should be directly related to the spectral state., 9 pages, 5 figures

Matter accreting onto black holes has long been known to have standing or oscillating shock waves. The post-shock matter puffs up in the form of a torus, which intercepts soft photons from the outer Keplerian disc and inverse Comptonizes to produce hard photons. The post-shock region also produces jets. We study the interaction of both hard photons and soft photons, with on-axis electron-positron jets. We show that the radiation from post-shock torus accelerates the flow to relativistic velocities, while that from the Keplerian disc has marginal effect. We also show that, the velocity at infinity or terminal velocity ${\vartheta}$, depends on the shock location in the disc., 24 pages, 8 figures, accepted in MNRAS

Bulk motion Comptonization utilizes properties of both matter and radiation close to the horizon of a black hole. Computation with these considerations produce hard tails of energy spectral slope $\sim 1.5-1.7$. These are the most direct evidence of the horizon of a black hole. We argue that even in presence of winds and outflows this property is not likely to change as winds are negligible in soft states., Comment: World Scientific Style. Proceedings of the 9th Marcel Grossman Meeting in Rome (World Scientific, to appear)

Jets and outflows are known to form out of advective accretion flows around black holes. Hard photons from the centrifugal barrier directly hit the electrons and deposit momentum on them. For optically thick flows such deposition is not efficient, but for optically thin flows matter could be accelerated to relativistic speed. In fact, even bound matter could be made free through successive deposition. We discuss these possibilities., Comment: AIP Publication, Macro included

We compute locations of sonic points and standing shock waves in a thin, axisymmetric, adiabatic flow around a Schwarzschild black hole. We use completely analytical method to achieve our goal. Our results are compared with those obtained numerically and a good agreement is seen. Our results positively prove the existence of shocks in centrifugal pressure dominated flows. We indicate how our results could be used to obtain spectral properties and frequencies of shock oscillations which may be directly related to the quasi-periodic oscillations of hard X-rays., Comment: Astrophysical Journal (In press, August 20th, 2001 issue)

We propose the processes of generation and radiative acceleration of jets from the centrifugal pressure dominated boundary layer around a black hole., Comment: World Scientific Style, macro included

2-Methoxyestradiol (2-ME2) is a novel anti-cancer agent because of its ability to potentiate apoptotic cell death and inhibit cancer cell growth and angiogenesis. In our study, we have investigated whether 2-ME2 is able to modulate epithelial-mesenchymal transition (EMT) in Barrett's esophageal adenocarcinoma cell (OE33), which has been postulated as an absolute requirement for tumor invasion and metastasis. Expression of epithelial (E-cadherin, β-catenin, Keratin-19) and mesenchymal markers (Oct-4, Vimentin) and stem cell markers (CD44, CD24) were studied at mRNA and protein levels in OE33 cells that were treated with 5µmolar/L of 2-ME2 for 24 h and 48 h. Our results indicate expression of β-catenin and E-cadherin is activated in a 2-ME2 dependent fashion in OE33 cells. Expression of Vimentin and Oct-4 is significantly down-regulated in 2-ME2 treated OE33 cells. Altogether, these results provide new insights into the role of 2-ME2 in EMT modulation, which may facilitate development of new therapeutic strategies to prevent the tumor invasion and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1684. doi:10.1158/1538-7445.AM2011-1684

In menopausal women, one of the important risk factors for breast cancer is obesity/adiposity. Despite multiple studies, the biological mechanism by which obesity influences the breast carcinogenic process is still unclear. It is evident from various studies that leptin, a 16 kDa protein hormone over produced in obese people, plays a critical role in neovascularization and tumorigenesis in breast and other organs. Present studies demonstrate that leptin is able to induce proliferation and migration of estrogen receptor positive MCF-7 and ZR-75-1 breast tumor cell lines in a dose-dependent fashion but these effects are minimal in ER-negative MDA-MB-231 cells. Additionally, these studies found that leptin suppresses the transcriptional activation of anti-invasive gene CCN5/WISP-2. Although the suppression of CCN5 has no impact on the constitutive proliferation of these cells, it is critical for leptin-induced proliferation and necessary for the induction of in vitro migration of these cells because the addition of CCN5 recombinant protein into the media markedly inhibits the leptin-induced proliferation and migration. Collectively, these in vitro studies suggest that CCN5 may serve as a gatekeeper for leptin dependent breast carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5540. doi:10.1158/1538-7445.AM2011-5540

CCN5/WISP-2 has been considered as an antiinvasive gene because CCN5/WISP-2 silencing augments the invasive phenotypes in vitro. One of the major functions of the CCN5 protein is to block aggressive behavior, such as the mesenchymal-to-epithelial transition (MET) of cancer cells. CCN5/WISP-2 is constitutively expressed in less aggressive human breast cancer cells, whereas its expression is undetected in the highly aggressive breast cancer cells. Dietary green tea polyphenol, (−)-epigallocatechin-3-gallate (EGCG), is believed to be an anticancer agent in part through its regulation of epigenetic processes. Our studies were aimed to address the epigenetic mechanisms of CCN5 reactivation by EGCG in highly aggressive breast cancer cells. In our current studies, we found that EGCG can reactivate CCN5 expression in highly aggressive breast cancer cell line (MDA-MB-231) and augments mesenchymal-epithelial transition process by modulating multiple EMT regulators. Combination studies using EGCG with the epigenetic modulators including the histone deacetylase (HDAC) inhibitor, trichostatin (TSA) and the DNA methyltransferase (DNMT) inhibitor such as 5-aza-2’-deoxycytidine (5- aza), revealed a synergistic effect of reactivation of CCN5 expression in highly aggressive breast cancer cells. Our findings help to assess the key mechanisms of EGCG chemoprevention and therapy by impacting epigenetic pathways toward aggressive breast tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2007. doi:10.1158/1538-7445.AM2011-2007

We investigated the instability of advective accretion flow as a consequence of angular momentum transfer in one-dimensional, quasi-spherical transonic accretion flow around a non-rotating black hole. The code is designed to include the effects of viscosity; the hydrodynamics component preserves angular momentum strictly with Lagrangian and remap method in absence of viscosity, while the viscosity component updates viscous angular momentum transfer through the implicit method. We performed two tests to demonstrate the suitability of the code for accretion study. First, we simulated the inviscid, low angular momentum, transonic accretion flow with shocks around a black hole, and then the subsonic, self-similar ADAF solution around a Newtonian object. Both simulations fitted the corresponding analytical curves extremely well. We then simulated a rotating, viscous, transonic fluid with shocks. We showed that for low viscosity parameter, stable shocks at larger distance are possible. For higher viscosity parameter, more efficient angular momentum transfer in the post-shock disk makes the shock structure oscillatory. Moreover, as the shock drifts to larger distances, a secondary inner shock develops. We showed that the inner shock is the direct consequence of expansion of the outer shock, as well as creation of regions with $\partial l / \partial r < 0$ due to more efficient angular momentum transfer near the inner sonic point. We showed that all disk parameters, including emissivity, oscillate with the same period as that of the shock oscillation. Our simulation may have implication for low frequency QPOs, e.g., GRO J1655-40 and XTE J1550-564., Accepted for publication in ApJ, 19 pages, 12 figures