58 research outputs found
Einstein Gravity and Beyond: Aspects of Higher-Curvature Gravity and Black Holes
No full textabstract: This thesis explores the different aspects of higher curvature gravity. The "membrane paradigm" of black holes in Einstein gravity is extended to black holes in f(R) gravity and it is shown that the higher curvature effects of f(R) gravity causes the membrane fluid to become non-Newtonian. Next a modification of the null energy condition in gravity is provided. The purpose of the null energy condition is to filter out ill-behaved theories containing ghosts. Conformal transformations, which are simple redefinitions of the spacetime, introduces serious violations of the null energy condition. This violation is shown to be spurious and a prescription for obtaining a modified null energy condition, based on the universality of the second law of thermodynamics, is provided. The thermodynamic properties of the black holes are further explored using merger of extremal black holes whose horizon entropy has topological contributions coming from the higher curvature Gauss-Bonnet term. The analysis refutes the prevalent belief in the literature that the second law of black hole thermodynamics is violated in the presence of the Gauss-Bonnet term in four dimensions. Subsequently a specific class of higher derivative scalar field theories called the galileons are obtained from a Kaluza-Klein reduction of Gauss-Bonnet gravity. Galileons are null energy condition violating theories which lead to violations of the second law of thermodynamics of black holes. These higher derivative scalar field theories which are non-minimally coupled to gravity required the development of a generalized method for obtaining the equations of motion. Utilizing this generalized method, it is shown that the inclusion of the Gauss-Bonnet term made the theory of gravity to become higher derivative, which makes it difficult to make any statements about the connection between the violation of the second law of thermodynamics and the galileon fields.Dissertation/ThesisDoctoral Dissertation Physics 201
Fast identification of biological pathways associated with a quantitative trait using group lasso with overlaps.
No full textWhere causal SNPs (single nucleotide polymorphisms) tend to accumulate within biological pathways, the incorporation of prior pathways information into a statistical model is expected to increase the power to detect true associations in a genetic association study. Most existing pathways-based methods rely on marginal SNP statistics and do not fully exploit the dependence patterns among SNPs within pathways.We use a sparse regression model, with SNPs grouped into pathways, to identify causal pathways associated with a quantitative trait. Notable features of our "pathways group lasso with adaptive weights" (P-GLAW) algorithm include the incorporation of all pathways in a single regression model, an adaptive pathway weighting procedure that accounts for factors biasing pathway selection, and the use of a bootstrap sampling procedure for the ranking of important pathways. P-GLAW takes account of the presence of overlapping pathways and uses a novel combination of techniques to optimise model estimation, making it fast to run, even on whole genome datasets.In a comparison study with an alternative pathways method based on univariate SNP statistics, our method demonstrates high sensitivity and specificity for the detection of important pathways, showing the greatest relative gains in performance where marginal SNP effect sizes are small
On coupling NEC-violating matter to gravity
No full textabstract: We show that effective theories of matter that classically violate the null energy condition cannot be minimally coupled to Einstein gravity without being inconsistent with both string theory and black hole thermodynamics. We argue however that they could still be either non-minimally coupled or coupled to higher-curvature theories of gravity.The final version of this article, as published in Physics Letters B, can be viewed online at: http://www.sciencedirect.com/science/article/pii/S0370269315001835?via%3Dihu
A Manual of Colloquial Hindustani and Bengali. By N. C. Chatterjee, Superintendent Board of Examiners, Calcutta. Published at Calcutta by the Author, 1914. Price, Rs. 2.8.
No full textA multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.
No full textWe conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis
Author Correction: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
No full textauthor correctio
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
No full textObesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation
Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study.
No full textINTRODUCTION: Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. METHODS: We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. RESULTS: These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. CONCLUSIONS: The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified
Silica nanoparticles and their interaction with cells : a multidisciplinary approach
No full textSilica nanoparticles are increasingly used as drug delivery systems and for biomedical imaging.
Therapeutic and diagnostic agents can be incorporated into the silica matrix to improve the stability
and solubility of hydrophobic drugs in biological systems. However, the safety of silica
nanoparticles as drug carriers remains controversial. To date, no validated and accepted nanospecific
tests exist to predict the potentially harmful impact of these materials on the human body.
The mechanism proposed for hemolysis of unmodified silica nanoparticles is based on the electrostatic
interaction between the silanol surface groups and the quaternary ammonium in the choline
head group of the phospholipids. However, a detailed understanding of this process is missing.
In this thesis, different silica nanoparticles where synthesized, characterized, and tested in two cell
lines regarding viability and oxidative stress. Hemolysis was assessed using red blood cells. Furthermore,
the hemolytic mechanism of a chosen silica nanoparticle type was investigated in depth
using a biophysical chemistry approach. We used the dye-leakage assay, isothermal titration
calorimetry, solid state nuclear magnetic resonance, and flow cytometry to elucidate this mechanism.
Our results revealed that silica nanoparticles with a porous surface and negative surface charge
had the strongest impact on viability in a concentration dependent manner. This is in contrast to
non-porous silica nanoparticles. None of the studied particles caused oxidative stress in either cell
lines. Particles with a negative surface charge induced hemolysis. The mechanism responsible for
the hemolysis for silica nanoparticles had no electrostatic component. The nuclear magnetic resonance
data revealed no interaction with the choline group. However, nuclear magnetic resonance
data suggested the presence of faster tumbling species.
Our toxicological and mechanistic studies showed potential hazards of spherical amorphous silica
nanoparticles. Physico-chemical properties mediating toxicity in living cells were identified.
We propose that our standardized silica nanoparticles may serve as a readily available reference
material for nanotoxicological investigations. Mechanistic data did not support an electrostatic
interaction as postulated in the literature, but rather a strong adsorption process that may lead
to hemolysis. Furthermore, the presence of faster tumbling species suggested the formation of
smaller lipid bilayer structures upon silica nanoparticles exposure. Flow cytometry data revealed
that their size is about 100 nm. It remains to be proven if the bilayer wraps around the hemolytic
silica nanoparticles, if an exclusive formation of smaller species without wrapping is present, or
both of the aforementioned
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