Effect of rabbit antiserum to ovine LH on reproductive organs in male hamsters and guinea-pigs

Administration of rabbit antiserum to ovine luteinizing hormone to immature hamsters and guinea-pigs resulted in a significant decrease in the weights of testes, seminal vesicle and ventral prostate. The author wishes to thank Prof. N.R. Moudgal for his interest and Family Planning Foundation for financial assistance.

Technological-forecasting and research inputs in area of birth-control technology

Technological forecasting, defined as quantified probabilistic prediction of timings and degree of change in the technological parameters, capabilities desirability or needs at different times in the future, is applied to birth control technology (BCT) as a means of revealing the paths of most promising research through identifying the necessary points for breakthroughs. The present status of BCT in the areas of pills and the IUD, male contraceptives, immumological approaches, post-coital pills, abortion, sterilization, luteolytic agents, laser technologies, and control of the sex of the child, are each summarized and evaluated in turn. Fine mapping is done to identify the most potentially promising areas of BCT. These include efforts to make oral contraception easier, improvement of the design of the IUD, clinical evaluation of the male contraceptive danazol, the effecting of biochemical changes in the seminal fluid, and researching of immunological approaches and the effects of other new drugs such as prostaglandins. The areas that require immediate and large research inputs are oral contraception and the IUD. On the basis of population and technological forecasts, it is deduced that research efforts could most effectively aid countries like India through the immediate production of an oral contraceptive pill or IUD with long-lasting effects. Development of a pill for males or an immunization against pre gnancy would also have a significant impact. However, the major impediment to birth control programs to date is attitudes, which must be changed through education.

Oligosaccharides modulate the apoptotic activity of glycodelin

GlycodelinA (GdA), a multifunctional glycoprotein secreted at high concentrations by the uterine endometrium during the early phases of pregnancy, carries glycan chains on asparagines at positions N28 and N63. GdA purified from amniotic fluid is known to be a suppressor of T-cell proliferation, an inducer of T-cell apoptosis, and an inhibitorof sperm-zona binding in contrast to its glycoform, glycodelinS (GdS), which is secreted by the seminal vesicles into the seminal plasma. The oligosaccharide chains of GdA terminate in sialic acid residues, whereas those of GdS are not sialylated but are heavily fucosylated. Our previous work has shown that the apoptogenic activity of GdA resides in the protein backbone, and we have also demonstrated the importance of sialylation for the manifestation of GdA-induced apoptosis. Recombinant glycodelin (Gd) expressed in the Sf21 insec cell line yielded an apoptotically active Gd; however, the same geneexpressed in the insect cell line Tni produced apoptotically inactive Gd, as observed with the gene expressed in the Chinese hamster ovary(CHO) cell line and earlier in Pichia pastoris. Glycan analysis of the Tni and Sf21 cell line-expressed Gd proteins reveals differences in their glycan structures, which modulate the manifestation of apoptogenic activity of Gd. Through apoptotic assays carried out with the wild-type (WT) and glycosylation mutants of Gd expressed in Sf21 and Tni cells before and after mannosidase digestion, we conclude that the accessibility to the apoptogenic region of Gd is influenced by the size of the glycans.

Faster Algorithms for All-pairs Approximate Shortest Paths in Undirected Graphs

Let G - (V, E) be a weighted undirected graph having nonnegative edge weights. An estimate (delta) over cap (u, v) of the actual distance d( u, v) between u, v is an element of V is said to be of stretch t if and only if delta(u, v) <= (delta) over cap (u, v) <= t . delta(u, v). Computing all-pairs small stretch distances efficiently ( both in terms of time and space) is a well-studied problem in graph algorithms. We present a simple, novel, and generic scheme for all-pairs approximate shortest paths. Using this scheme and some new ideas and tools, we design faster algorithms for all-pairs t-stretch distances for a whole range of stretch t, and we also answer an open question posed by Thorup and Zwick in their seminal paper [J. ACM, 52 (2005), pp. 1-24].

Spectroscopic investigations of phase transitions in complex solids

Spectroscopic methods have provided information of seminal importance in understanding phase transitions in solids. After briefly examining some fundamental concept related to phase transitions, we shall discuss several case studies particularly involving the use of vibrational (IR and Raman) spectroscopy. Examples will include both order-disorder and displacive transitions. Under the former are included transitions in nitrates, ammonium halides, alkylammonium salts, plastic state of C60 and superionic conductors (specially CsHSO4). In addition, we shall discuss some aspects of incommensurate phase transitions, the glass transition and electronic phase transitions. Transitions of phosphonitrilic halide tetramers and alkane dicarboxylic acids are also examined

Responsiveness of human male volunteers to immunization with ovine follicle stimulating hormone vaccine: Results of a pilot study

A study of 140 days duration was performed to examine if human male volunteers (n = 5) respond to ovine follicle stimulating hormone (oFSH) immunization (administered adsorbed on Alugel on days 1, 20, 40 and 70) by producing antibodies capable of both binding and neutralizing bioactivity of human FSH. The kinetics of antibody production for both the immunogen (oFSH) and the cross-reactive antigen (hFSH) were essentially similar, The volunteers responded only to the first two immunizations, The boosters given on days 40 and 70 were ineffective, probably because of the presence of substantial amounts of circulating antibody to oFSH. Of the antibodies generated to oFSH, 25-45% bound hFSH with a mean binding affinity of 0.65 x 10(9) +/- 0.53 M(-1). The binding capacities at the time of high (30-80 days of immunization) and low (>110 days) titres were 346 +/- 185 and 10.5 +/- 5.8 ng hFSH/ml respectively, During the period of high titre, free serum FSH (value in normal males 1-5 ng/ml) was not monitorable, A 50 mu l aliquot of the antiserum obtained from different volunteers between days 30 and 80 and on day 140 blocked binding of I-125-labelled hFSH to its receptor by 82 +/- 9.7 and 53 +/- 12.2% respectively, The antibody produced was specific for FSH, and no significant change in the values of related glycoprotein hormones (luteinizing hormone/testosterone and thyroid stimulating hormone/thyroxine) were recorded, Seminal plasma transferrin, a marker of Sertoli cell as well as of seminiferous tubular function, showed marked reduction (30-90%) following immunization with oFSH. Considering that endogenous FSH remained neutralized for approximately one sperm cycle only (65 days), the reduction in sperm counts (30-74%) exhibited by some volunteers is encouraging, Immunization with oFSH did not result in any significant changes in haematology, serum biochemistry or hormonal profiles, There was no production of antibodies capable of interacting with non-specific tissues, It is concluded that it should be possible to obtain a sustained long-term blockade of endogenous FSH action in men by using oFSH as an immunogen, This is a prerequisite for obtaining significant reduction in the quality and quantity of spermatozoa produced, thus leading to infertility.

Multi-scale interactions and predictability of the Indian summer monsoon

Following the seminal work of Charney and Shukla (198 1), the tropical climate is recognised to be more predictable than extra tropical climate as it is largely forced by 'external' slowly varying forcing and less sensitive to initial conditions. However, the Indian summer monsoon is an exception within the tropics where 'internal' low frequency (LF) oscillations seem to make significant contribution to its interannual variability (IAV) and makes it sensitive to initial conditions. Quantitative estimate of contribution of 'internal' dynamics to IAV of Indian monsoon is made using long experiments with an atmospheric general circulation model (AGCM) and through analysis of long daily observations. Both AGCM experiments and observations indicate that more than 50% of IAV of the monsoon is contributed by 'internal' dynamics making the predictable signal (external component) burried in unpredictable noise (internal component) of comparable amplitude. Better understanding of the nature of the 'internal' LF variability is crucial for any improvement in predicition of seasonal mean monsoon. Nature of 'internal' LF variability of the monsoon and mechanism responsible for it are investigated and shown that vigorous monsoon intraseasonal oscillations (ISO's) with time scale between 10-70 days are primarily responsible for generating the 'internal' IAV. The monsoon ISO's do this through scale interactions with synoptic disturbances (1-7 day time scale) on one hand and the annual cycle on the other. The spatial structure of the monsoon ISO's is similar to that of the seasonal mean. It is shown that frequency of occurance of strong (weak) phases of the ISO is different in different seasons giving rise to stronger (weaker) than normal monsoon. Change in the large scale circulation during strong (weak) phases of the ISO make it favourable (inhibiting) for cyclogenesis and gives rise to space time clustering of synoptic activity. This process leads to enhanced (reduced) rainfall in seasons of higher frequency of occurence strong (weak) phases of monsoon ISO.

A finite population model of mlecular evolution: theory and computation

This article is concerned with the evolution of haploid organisms that reproduce asexually. In a seminal piece of work, Eigen and coauthors proposed the quasispecies model in an attempt to understand such an evolutionary process. Their work has impacted antiviral treatment and vaccine design strategies. Yet, predictions of the quasispecies model are at best viewed as a guideline, primarily because it assumes an infinite population size, whereas realistic population sizes can be quite small. In this paper we consider a population genetics-based model aimed at understanding the evolution of such organisms with finite population sizes and present a rigorous study of the convergence and computational issues that arise therein. Our first result is structural and shows that, at any time during the evolution, as the population size tends to infinity, the distribution of genomes predicted by our model converges to that predicted by the quasispecies model. This justifies the continued use of the quasispecies model to derive guidelines for intervention. While the stationary state in the quasispecies model is readily obtained, due to the explosion of the state space in our model, exact computations are prohibitive. Our second set of results are computational in nature and address this issue. We derive conditions on the parameters of evolution under which our stochastic model mixes rapidly. Further, for a class of widely used fitness landscapes we give a fast deterministic algorithm which computes the stationary distribution of our model. These computational tools are expected to serve as a framework for the modeling of strategies for the deployment of mutagenic drugs.

Genome-wide methylation profiling identifies an essential role of reactive oxygen species in pediatric glioblastoma multiforme and validates a methylome specific for H3 histone family 3A with absence of G-CIMP/isocitrate dehydrogenase 1 mutation

Background. Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH) 1 mutation with a DNA methylation signature. The present study aims to validate these findings in an independent cohort of pediatric GBM, compare it with adult GBM, and evaluate the involvement of important functionally altered pathways. Methods. Genome-wide methylation profiling of 21 pediatric GBM cases was done and compared with adult GBM data (GSE22867). We performed gene mutation analysis of IDH1 and H3 histone family 3A (H3F3A), status evaluation of glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP), and Gene Ontology analysis. Experimental evaluation of reactive oxygen species (ROS) association was also done. Results. Distinct differences were noted between methylomes of pediatric and adult GBM. Pediatric GBM was characterized by 94 hypermethylated and 1206 hypomethylated cytosine-phosphate-guanine (CpG) islands, with 3 distinct clusters, having a trend to prognostic correlation. Interestingly, none of the pediatric GBM cases showed G-CIMP/IDH1 mutation. Gene Ontology analysis identified ROS association in pediatric GBM, which was experimentally validated. H3F3A mutants (36.4%; all K27M) harbored distinct methylomes and showed enrichment of processes related to neuronal development, differentiation, and cell-fate commitment. Conclusions. Our study confirms that pediatric GBM has a distinct methylome compared with that of adults. Presence of distinct clusters and an H3F3A mutation-specific methylome indicate existence of epigenetic subgroups within pediatric GBM. Absence of IDH1/G-CIMP status further indicates that findings in adult GBM cannot be simply extrapolated to pediatric GBM and that there is a strong need for identification of separate prognostic markers. A possible role of ROS in pediatric GBM pathogenesis is demonstrated for the first time and needs further evaluation.