Seismic Stability Analysis of a Himalayan Rock Slope

The seismic slope stability analysis of the right abutment of a railway bridge proposed at about 350 m above the ground level, crossing a river and connecting two huge hillocks in the Himalayas, India, is presented in this paper. The rock slopes are composed of highly jointed rock mass and the joint spacing and orientation are varying at different locations. Seismic slope stability analysis of the slope under consideration is carried out using both pseudo-static approach and time response approach as the site is located in seismic zone V as per the earth quake zonation maps of India. Stability of the slope is studied numerically using program FLAC. The results obtained from the pseudo-static analysis are presented in the form of Factor of Safety (FOS) and the results obtained from the time response analysis of the slope are presented in terms of horizontal and vertical displacements along the slope. The results obtained from both the analyses confirmed the global stability of the slope as the FOS in case of pseudo-static analysis is above 1.0 and the displacements observed in case of time response analysis are within the permissible limits. This paper also presents the results obtained from the parametric analysis performed in the case of time response analysis in order to understand the effect of individual parameters on the overall stability of the slope.

Generating artificial chromosomes with probability control in genetic algorithm for machine scheduling problems

In this paper, a novel genetic algorithm is developed by generating artificial chromosomes with probability control to solve the machine scheduling problems. Generating artificial chromosomes for Genetic Algorithm (ACGA) is closely related to Evolutionary Algorithms Based on Probabilistic Models (EAPM). The artificial chromosomes are generated by a probability model that extracts the gene information from current population. ACGA is considered as a hybrid algorithm because both the conventional genetic operators and a probability model are integrated. The ACGA proposed in this paper, further employs the ``evaporation concept'' applied in Ant Colony Optimization (ACO) to solve the permutation flowshop problem. The ``evaporation concept'' is used to reduce the effect of past experience and to explore new alternative solutions. In this paper, we propose three different methods for the probability of evaporation. This probability of evaporation is applied as soon as a job is assigned to a position in the permutation flowshop problem. Experimental results show that our ACGA with the evaporation concept gives better performance than some algorithms in the literature.

Genetic and epigenetic mechanisms of tumor predisposition in hereditary non-polyposis colorectal carcinoma and sporadic cancers

Individuals with inherited deficiency in DNA mismatch repair(MMR) (Lynch syndrome) LS are predisposed to different cancers in a non-random fashion. Endometrial cancer (EC) is the most common extracolonic malignancy in LS. LS represents the best characterized form of hereditary nonpolyposis colorectal carcinoma (HNPCC). Other forms of familial non-polyposis colon cancer exist, including familial colorectal cancer type X (FCCX). This syndrome resembles LS, but MMR gene defects are excluded and the predisposition genes are unknown so far. To address why different organs are differently susceptible to cancer development, we examined molecular similarities and differences in selected cancers whose frequency varies in LS individuals. Tumors that are common (colorectal, endometrial, gastric) and less common (brain, urological) in LS were characterized for MMR protein expression, microsatellite instability (MSI), and by altered DNA methylation. We also studied samples of histologically normal endometrium, endometrial hyperplasia,and cancer for molecular alterations to identify potential markers that could predict malignant transformation in LS and sporadic cases. Our results suggest that brain and kidney tumors follow a different pathway for cancer development than the most common LS related cancers.Our results suggest also that MMR defects are detectable in endometrial tissues from a proportion of LS mutation carriers prior to endometrial cancer development. Traditionally (complex) atypical hyperplasia has been considered critical for progression to malignancy. Our results suggest that complex hyperplasia without atypia is equally important as a precursor lesion of malignancy. Tumor profiles from Egypt were compared with colorectal tumors from Finland to evaluate if there are differences specific to the ethnic origin (East vs.West). Results showed for the first time a distinct genetic and epigenetic signature in the Egyptian CRC marked by high methylation of microsatellite stable tumors associated with advanced stage, and low frequency of Wnt signaling activation, suggesting a novel pathway. DNA samples from FCCX families were studied with genome wide linkage analysis using microsatellite markers. Selected genes from the linked areas were tested for possible mutations that could explain predisposition to a large number of colon adenomas and carcinomas seen in these families. Based on the results from the linkage analysis, a number of areas with tentative linkage were identified in family 20. We narrowed down these areas by additional microsatellite markers to found a mutation in the BMPR1A gene. Sequencing of an additional 17 FCCX families resulted in a BMPR1A mutation frequency of 2/18 families (11%). Clarification of the mechanisms of the differential tumor susceptibility in LS increases the understanding of gene and organ specific targets of MMR deficiency. While it is generally accepted that widespread MMR deficiency and consequent microsatellite instability (MSI) drives tumorigenesis in LS, the timing of molecular alterations is controversial. In particular, it is important to know that alterations may occur several years before cancer formation, at stages that are still histologically regarded as normal. Identification of molecular markers that could predict the risk of malignant transformation may be used to improve surveillance and cancer prevention in genetically predisposed individuals. Significant fractions of families with colorectal and/or endometrial cancer presently lack molecular definition altogether. Our findings expand the phenotypic spectrum of BMPR1A mutations and, for the first time, link FCCX families to the germline mutation of a specific gene. In particular, our observations encourage screening of additional families with FCCX for BMPR1A mutation, which is necessary in obtaining a reliable estimate of the share of BMPR1A-associated cases among all FCCX families worldwide. Clinically, the identification of predisposing mutations enables targeted cancer prevention in proven mutation carriers and thereby reduces cancer morbidity and mortality in the respective families.

Solubility and physical stability improvement of natiral xanthine derivatives

Use of natural xanthine derivates in medicine is complicated with their physical properties. Theobromine is poorly soluble while theophylline is highly sensitive to hydration. The aim of this study was to improve bioavailability of xanthines by co-crystallization, theophylline was also cocrystallized with carboxylic acids (capric, citric, glutaric, malenic, malonic, oxalic, stearic, succinic) and HPMC. Co-crystallization was performed by slow evaporation and ball milling. Physical stability was checked by wet granulation and water sorption methods, solubility was measured by intrinsic tablet dissolution. Theobromine formed co-crystal with other xanthines and theophylline interacted with all acids except stearic and HPMC, the latter showed alternative interactions based on hydrogen bonding. Hydration resistance was good in theophylline:succinic acid co-crystal and excellent in complexes containing capric, stearic acids and HPMC. Theophylline:HPMC showed improved solubility. The reported approach can promote use of xanthines and can be recommended for other compounds with similar problems.

Structure and thermal stability relationships in ring-substituted arylammonium nitrates

The thermal stability of ring-substituted arylammonium nitrates has been investigated using thermal methods of analysis. The decomposition temperature of meta- and para-substituted derivatives is found to be linearly related to the Hammett substituent constant σ. The activation energy for decomposition determined by isothermal gravimetry increases with the increasing basicity of the corresponding amine. The results suggest that the primary step in the decomposition process of these salts is proton abstraction by the anion from the arylammonium ion.

Microcycle conidiation and its genetic basis in Neurospora crassa

Some wild isolates of Neurospora show microcycle conidiation in liquid culture under continuous agitation. Macroconidia from agar-grown mycelial cultures germinated in liquid and the germlings spontaneously produced conidia with no intervening mycelial phase. Three types of microcycle conidiation were seen among progeny of N. crassa Vickramam A x N. crassa a wild-type: (1) multinucleate blastoconidia produced by apical budding and septation, (2) multinucleate arthroconidia produced by holothallic septation and disarticulation of cells, and (3) uninucleate microconidia produced directly from conidiogenous cells of the germlings. Two genes were identified which control specific patterns of microcycle conidiogenesis. A single gene mcb in linkage group VR near al-3 (3.2% recombination) controls blastoconidiation. This gene is epistatic to gene mcm located in linkage group IIL, very near ro-7 (1.4%). mcm controls both microconidiation and arthroconidiation depending on temperature. Strains of genotype mcm produce microconidia almost exclusively at 18-22 degrees C, but arthroconidia with few or no microconidia at 30 degrees C. Because they result in rapid and synchronized conidiation in liquid culture, the two genes should be useful for studies of developmental gene regulation. mcm makes it possible to obtain large quantities of pure microconidia rapidly for experimentation.

Genetic polymorphisms and laboratory variables as predictors of blood pressure response to antihypertensive drugs

Hypertension is one of the major risk factors for cardiovascular morbidity. The advantages of antihypertensive therapy have been clearly demonstrated, but only about 30% of hypertensive patients have their blood pressure (BP) controlled by such treatment. One of the reasons for this poor BP control may lie in the difficulty in predicting BP response to antihypertensive treatment. The average BP reduction achieved is similar for each drug in the main classes of antihypertensive agents, but there is a marked individual variation in BP responses to any given drug. The purpose of the present study was to examine BP response to four different antihypertensive monotherapies with regard to demographic characteristics, laboratory test results and common genetic polymorphisms. The subjects of the present study are participants in the pharmacogenetic GENRES Study. A total of 208 subjects completed the whole study protocol including four drug treatment periods of four weeks, separated by four-week placebo periods. The study drugs were amlodipine, bisoprolol, hydrochlorothiazide and losartan. Both office (OBP) and 24-hour ambulatory blood pressure (ABP) measurements were carried out. BP response to study drugs were related to basic clinical characteristics, pretreatment laboratory test results and common polymorphisms in genes coding for components of the renin-angiotensin system, alpha-adducin (ADD1), beta1-adrenergic receptor (ADRB1) and beta2-adrenergic receptor (ADRB2). Age was positively correlated with BP responses to amlodipine and with OBP and systolic ABP responses to hydrochlorothiazide, while body mass index was negatively correlated with ABP responses to amlodipine. Of the laboratory test results, plasma renin activity (PRA) correlated positively with BP responses to losartan, with ABP responses to bisoprolol, and negatively with ABP responses to hydrochlorothiazide. Uniquely to this study, it was found that serum total calcium level was negatively correlated with BP responses to amlodipine, whilst serum total cholesterol level was negatively correlated with ABP responses to amlodipine. There were no significant associations of angiotensin II type I receptor 1166A/C, angiotensin converting enzyme I/D, angiotensinogen Met235Thr, ADD1 Gly460Trp, ADRB1 Ser49Gly and Gly389Arg and ADRB2 Arg16Gly and Gln27Glu polymorphisms with BP responses to the study drugs. In conclusion, this study confirmed the relationship between pretreatment PRA levels and response to three classes of antihypertensive drugs. This study is the first to note a significant inverse relation between serum calcium level and responsiveness to a calcium channel blocker. However, this study could not replicate the observations that common polymorphisms in angiotensin II type I receptor, angiotensin converting enzyme, angiotensinogen, ADD1, ADRB1, or ADRB2 genes can predict BP response to antihypertensive drugs.

Hostility: A prospective study of the genetic and environmental background and associations with cardiovascular risk

Hostility is a multidimensional construct having wide effects on society. In its different forms, hostility is related to a large array of social and health problems, such as criminality, substance abuse, depression, and cardiovascular risks. Identifying and tackling early-life factors that contribute to hostility may have public health significance. Although the variance in hostility is estimated to be 18-50 percent heritable, there are significant gaps in knowledge regarding the molecular genetics of hostility. It is known that a cold and unsupportive home atmosphere in childhood predicts a child s later hostility. However, the long-term effects of care-giving quality on hostility in adulthood and the role of genes in this association are unclear. The present dissertation is part of the ongoing population-based prospective Young Finns study, which commenced in 1980 with 3596 3-18-year-old boys and girls who were followed for 27 years. The specific aims of the dissertation were first to study the antecedents of hostility by looking at 1) the genetic background, 2) the early environmental predictors, and 3) the gene environment interplay behind hostility. As a second aim, the thesis endeavored to examine 4) the association between hostility and cardiovascular risks, and 5) the moderating effect of demographic factors, such as gender and socioeconomic status, on this association. The study found potential gene polymorphisms from chromosomes 7, 14, 17, and 22 suggestively associated with hostility. Of early environmental influences, breastfeeding and early care-giving were found to predict hostility in adulthood. In addition, a serotonin receptor 2A polymorphism rs6313 moderated the effect of early care-giving on later hostile attitudes. Furthermore, hostility was shown to predict cardiovascular risks, such as metabolic syndrome and inflammation. Finally, parental socioeconomic status was found to moderate the association between anger and early atherosclerosis. The new genetic and early environmental antecedents of hostility identified in this research may help in understanding the development of hostility and its health risks, and in planning appropriate prevention. The significance of early influences on this development is stressed. Although the markers studied are individual- and family-related factors, these may be influenced at the societal level by giving accurate information to all individuals concerned and by improving the societal circumstances.

Tuning and stability of a singly resonant continuous-wave optical parametric oscillator close to degeneracy

Wavelength tuning and stability characteristics of a singly resonant continuous-wave optical parametric oscillator (cw OPO) in the proximity of signal-idler degeneracy have been studied. The OPO is made singly resonant by using a Bragg grating as a spectral filter in the OPO cavity. The signal-idler frequency difference can be tuned from 0.5 to 7 THz, which makes the OPO suitable for cw THz generation by optical heterodyning. The operation of the OPO within this singly-resonant regime is characterized by a strong self-stabilization effect. A gradual transition to an unstable, doubly-resonant regime is observed for a signal-idler detuning smaller than ~ 0.5 THz.

Compensator for constant relative stability in process control systems

Process control systems are designed for a closed-loop peak magnitude of 2dB, which corresponds to a damping coefficient () of 0.5 approximately. With this specified constraint, the designer should choose and/or design the loop components to maintain a constant relative stability. However, the manipulative variable in almost all chemical processes will be the flow rate of a process stream. Since the gains and the time constants of the process will be functions of the manipulative variable, a constant relative stability cannot be maintained. Up to now, this problem has been overcome either by selecting proper control valve flow characteristics or by gain scheduling of controller parameters. Nevertheless, if a wrong control valve selection is made then one has to account for huge loss in controllability or eventually it may lead to an unstable control system. To overcome these problems, a compensator device that can bring back the relative stability of the control system was proposed. This compensator is similar to a dynamic nonlinear controller that has both online and offline information on several factors related to the control system. The design and analysis of the proposed compensator is discussed in this article. Finally, the performance of the compensator is validated by applying it to a two-tank blending process. It has been observed that by using a compensator in the process control system, the relative stability could be brought back to a great extent despite the effects of changes in manipulative flow rate.

RAD51C: a novel cancer susceptibility gene is linked to Fanconi anemia and breast cancer

Germline mutations in many of the genes that are involved in homologous recombination (HR)-mediated DNA double-strand break repair (DSBR) are associated with various human genetic disorders and cancer. RAD51 and RAD51 paralogs are important for HR and in the maintenance of genome stability. Despite the identification of five RAD51 paralogs over a decade ago, the molecular mechanism(s) by which RAD51 paralogs regulate HR and genome maintenance remains obscure. In addition to the known roles of RAD51C in early and late stages of HR, it also contributes to activation of the checkpoint kinase CHK2. One recent study identifies biallelic mutation in RAD51C leading to Fanconi anemia-like disorder. Whereas a second study reports monoallelic mutation in RAD51C associated with increased risk of breast and ovarian cancer. These reports show RAD51C is a cancer susceptibility gene. In this review, we focus on describing the functions of RAD51C in HR, DNA damage signaling and as a tumor suppressor with an emphasis on the new roles of RAD51C unveiled by these reports.