Design sensitivity analysis of nonlinear structural response

A unified theory is described of design sensitivity analysis of linear and nonlinear structures for shape, nonshape and material selection problems. The concepts of reference volume and adjoint structure are used to develop the unified viewpoint. A general formula for design sensitivity analysis is derived. Simple analytical linear and nonlinear examples are used to interpret various terms of the formula and demonstrate its use

Strong inapproximability of the shortest reset word

The \v{C}ern\'y conjecture states that every $n$-state synchronizing automaton has a reset word of length at most $(n-1)^2$. We study the hardness of finding short reset words. It is known that the exact version of the problem, i.e., finding the shortest reset word, is NP-hard and coNP-hard, and complete for the DP class, and that approximating the length of the shortest reset word within a factor of $O(\log n)$ is NP-hard [Gerbush and Heeringa, CIAA'10], even for the binary alphabet [Berlinkov, DLT'13]. We significantly improve on these results by showing that, for every $\epsilon>0$, it is NP-hard to approximate the length of the shortest reset word within a factor of $n^{1-\epsilon}$. This is essentially tight since a simple $O(n)$-approximation algorithm exists.Comment: extended abstract to appear in MFCS 201

Functional characterization of antigen repertoires in HLA-associated complex diseases to investigate antagonistic selection on HLA genes

The interaction between hosts and pathogens represents a major driver of their evolution, and a core interest in the evolutionary biology. In vertebrate hosts, the classical genes of Major Histocompatibility Complex (MHC) make a central component of their adaptive immune system. The cell-surface molecules encoded by the MHC genes present peptide fragments (derived from both self-antigens and pathogens) to T-cells, which upon recognizing them as foreign, initiate a specific immune response. To explore the general MHC evolution, I used humans as a study system where MHC is designated as Human Leukocyte Antigen (HLA). Although a vast allelic diversity of HLA genes exists at the population level, potentially maintained by pathogen-mediated balancing selection, only a fraction of that is seen at the individual level in the form of a limited number of HLA genes and their alleles. This setting has been proposed as an optimum between HLAconferred resistance to pathogens and the risk of autoimmunity, which represent major antagonistic selection forces on HLA genes. The fine-mapping of various HLA’s association with different infectious and autoimmune diseases has suggested a major role of the peptide-repertoire of HLA alleles in determining their specific effect on diseases. However, the exact mechanisms that underlie HLA’s association with the diseases, and by that modulate the antagonistic selection on HLA genes remain elusive. In order to elucidate them, I started by investigating the functional basis of the previously known protective effect of HLA heterozygosity at the HLA class-I genes on HIV-1 progression. I used a dataset of 6,311 HIV-1 infected individuals and predicted the HLAbound peptides derived from HIV-1 proteome for each HLA allele represented in the dataset. The individual-specific repertoire of HLA-bound peptides suggested that HLA heterozygote advantage against HIV-1 could be mediated by both a broader array of HLAbound peptides and a higher likelihood of carrying specific protective alleles in heterozygotes compared to homozygotes. The comparison of the peptide-repertoire of risk and protective alleles suggested that individual alleles could confer disease control by binding either a large number of peptides or specific immunodominant peptides. The separate analysis of the individual HLA genes indicated that different mechanism for the heterozygote advantage might work at different genes, such as either T-cell or NK-cellmediated immune attack on the virus, possibly resulting in different evolutionary constraints on different HLA genes. Overall, the findings suggested that the pathogenmediated selection might favor both HLA heterozygosity and individual alleles. hypothesizing that not all HLA-bound peptides would be relevant for disease control, we developed a new approach, named Peptidome-wide association study (PepWAS), that can predict HLA-bound disease-associated epitopes from a given peptidome. The PepWAS-predicted HIV-1-associated epitopes accounted for as much variation (12%) in HIV-1 viral load as by the genetic variants in HLA class-I genes, providing a functional basis for the association between HLA and HIV-1 control. I then focused on the association between HLA class-II genes and Type 1 Diabetes (T1D). Using a case-control dataset of 16,029 individuals, I first showed that heterozygosity at the HLA class-II genes conferred T1D risk. To investigate functional basis of this HLA heterozygote disadvantage, I predicted individual-specific repertoires of HLA-bound peptides from 17 T1D-relevant human proteins. The comparison of individual-specific peptide-repertoires between HLA heterozygous and homozygous individuals suggested that both a broader array of HLA-bound self-peptides and higher odds of carrying risk alleles might contribute to HLA heterozygote disadvantage. The characterization of the allele-specific peptide-repertoire suggested that an allele might confer T1D risk due to its low peptide-binding affinity possibly contributing to inefficient removal of autoreactive T-cells in thymus and (or) by binding specific disease-causing peptides, e.g. posttranslationally deamidated peptides. The PepWAS-predicted T1D-associated epitopes accounted for even more deviance in T1D status than HLA class-II haplotypes (33.1 vs. 29.6%). Moreover, the sequence homology between predicted T1D-associated epitopes and pathogenic peptides suggested pathogens as the potential trigger of autoimmunity. Overall, the insights from this thesis shed light on different mechanisms that possibly underlie the differential association of HLA genes with infectious and autoimmune diseases, which, in turn, potentially shape the antagonistic selection on the classical HLA genes

Mesomorphic properties of alkoxybenzylidene- aminoacetophenones

Liquid crystal phase transitions in compounds of alkoxybenzylidene-aminoacetophene serie

On the NP-Hardness of Approximating Ordering Constraint Satisfaction Problems

We show improved NP-hardness of approximating Ordering Constraint Satisfaction Problems (OCSPs). For the two most well-studied OCSPs, Maximum Acyclic Subgraph and Maximum Betweenness, we prove inapproximability of $14/15+\epsilon$ and $1/2+\epsilon$. An OCSP is said to be approximation resistant if it is hard to approximate better than taking a uniformly random ordering. We prove that the Maximum Non-Betweenness Problem is approximation resistant and that there are width-$m$ approximation-resistant OCSPs accepting only a fraction $1 / (m/2)!$ of assignments. These results provide the first examples of approximation-resistant OCSPs subject only to P $\neq$ \NP

Aerobic bacterial pathogens in burn wound infections: experience in a teaching institution

Background: Infections are a serious cause of burn mortality and morbidity. Post initial resuscitation burn wound infections account for 75% of burn mortality. With rising number of multidrug resistant pathogens and changing microbiological colonizers of the burn wound, the insight provided by documenting the pathogens will help streamline the management. The aim of our study was to isolate, identify and study the profiles of aerobic bacteria in patients with burn wound infections.Methods: This was a hospital based observational study carried out in the department of microbiology and department of burns and plastics, Safdarjung hospital after obtaining hospital ethical committee approval. Day 1, day 3, day 5 and day 10 swabs from burn sites were taken and processed after taking proper aseptic precautions from a total of 100 patients.Results: Most of the aerobic isolates were gram negative in nature with K.pneumoniae (27.43%) being the most common followed by P. aeruginosa (22.12%), S. aureus (14.15%), P. mirabilis (10.61%), Acinetobacter spp (10.17%), CoNS (8.40%), E. coli (3.53%), P. stuartii (1.32%), Enterobacter spp (1.32%), K. oxytoca (0.44%) and C. koseri (0.44%).Conclusions: We concluded the study recognizing K. pneumoniae as the most common isolate that cause burn wound infections. Further studies which include anaerobic isolates are required for identifying full range of organism profile of burn wound infections.

On Fitting a Surface

This article deals with the problem of fitting the surface f=g (x) h(y) to the set of points (x/sub i/,y/sub j/,f/j). Functions g(x) and h(y) are supposed to be expressible in terms of orthonormal sets of functions. The desired coefficients of these functions are determined as characteristic vectors corresponding to the largest characteristic root of two materials having common characteristic roots

Reliability of a Modular Standby Redundant System with Unrecoverable Failures

This paper considers a stand by redundant system consisting of two identical modules. Each module is compose of N distinct components in series. The failure of a module may be attributed due to the failure of any of its N components. The ith components of a module has an arbitrary repair time CDF, G./sub i/ (t). The stand by module has been assumed to have a nonzero hazard rate even when unpowered. The failure of an on-line module is identified through a sensing device which has a probability 'c' of successfully recovering a fault in the on-line module. Expressions for the distribution of the Time to First System Failure (TFSF), the expected TFSF, and the reliability of the system have been derived by using the theory of Markov renewal processes