Solvent effect in molecular recognition: Determining binding constants in different solvents following an extraction based protocol

Semi-rigid molecular tweezers 1, 3 and 4 bind picric acid with more than tenfold increment in tetrachloromethane as compared to chloroform.

Immunization of male bonnet monkeys (M-radiata) with a recombinant FSH receptor preparation affects testicular function and fertility

Immunization of proven fertile adult male monkeys (n = 3) with a recombinant FSH receptor protein preparation (oFSHR-P) (representing amino acids 1-134 of the extracellular domain of the receptor Mr similar to 15KDa) resulted in production of receptor blocking antibodies. The ability of the antibody to bind a particulate FSH receptor preparation and receptors in intact granulosa cells was markedly (by 30-80%) inhibited by FSH. Serum T levels and LH receptor function following immunization remained unchanged. The immunized monkeys showed a 50% reduction (p<0.001) in transformation of spermatogonia(2C) to primary spermatocytes (4C) as determined by flow cytometry and the 4C:2C ratio showed a correlative change (R 0.81, p<0.0007) with reduction in fertility index (sperm counts X motility score). Breeding studies indicated that monkeys became infertile between 242-368 days of immunization when the fertility index was in the range of 123+/-76 to 354+/-42 (compared to a value of 1602+/-384 on day 0). As the effects observed ate near identical to that seen following immunization with FSH it is suggestive that oFSHR-P can substitute for FSH in the development of a contraceptive vaccine.

Mechanism of foetal wastage following immunoneutralization of riboflavin carrier protein in the pregnant rat: disturbances in flavin coenzyme levels

Immunoneutralization of maternal RCP results in a >90% decrease in the content and the incorporation of [2-14C]riboflavin into embryonic FAD as well as a percentage redistribution of both embryonic FMN and riboflavin. This is unaccompanied by any discernible changes in flavin distribution pattern in the maternal liver. Embryonic α-glycerophosphate dehydrogenase and NADPH-cytochrome c reductase register significant decreases in activities in the RCP antiserum-treated rats. These alterations readily explain the arrest of foetal growth culminating in pregnancy termination in the antiserum-treated animals.

Structured model-following neuro-adaptive design for attitude maneuver of rigid bodies

A new structured model-following adaptive approach is presented in this paper to achieve large attitude maneuvers of rigid bodies. First, a nominal controller is designed using the dynamic inversion philosophy. Next, a neuro- adaptive design is proposed to augment the nominal design in order to assure robust performance in the presence of parameter inaccuracies as well as unknown constant external disturbances. The structured approach proposed in this paper (where kinematic and dynamic equations are handled separately), reduces the complexity of the controller structure. From simulation studies, this adaptive controller is found to be very effective in assuring robust performance.

In Situ Phase Separation Following Dehydration in Bimetallic Sulfates: A Variable-Temperature X-Ray Diffraction Study

Phase separation resulting in a single-crystal-single-crystal transition accompanied by a polycrystalline phase following the dehydration of hydrated bimetallic sulfates [Na2Mn1.167(SO4)(2)S0.33O1.167 center dot 2H(2)O and K4Cd3-(SO4)(5)center dot 3H(2)O] has been investigated by in situ variable-temperature single-crystal X-ray diffraction. With two examples, we illustrate the possibility of generating structural frameworks following dehydration in bimetallic sulfates, which refer to the possible precursor phases at that temperature leading to the mineral formation. The room-temperature structure of Na2Mn1.167(SO4)(2)S0.33O1.167 center dot 2H(2)O is trigonal, space group R (3) over bar. On heating the crystal in situ on the diffractometer, the diffraction images display spherical spots and concentric rings suggesting phase separation, with the spherical spots getting indexed in a monoclinic space group, C2/c. The structure determination based on this data suggests the formation of Na2Mn(SO4)(2). However, the diffraction images from concentric rings could not be indexed. In the second example, the room-temperature structure is determined to be K4Cd3(SO4)(5)center dot 3H(2)O, crystallizing in a monoclinic space group, P2(1)/n. On heating the crystal in situ, the diffraction images collected also have both spherical spots and diffuse rings. The spherical spots could be indexed to a cubic crystal system, space group P2(1)3, and the structure is K4Cd3(SO4)(3). The possible mechanism for the phase transition in the dehydration regime resulting in this remarkable single-crystal to single-crystal transition with the appearance of a surrogate polycrystalline phase is proposed.

Electrophysiological correlates of hanseniasis

Sensory nerve action potentials (SNAPs) and compound nerve action potentials (CNAPs) were recorded from 25 normal subjects and 21 hanseniasis patients following electrical stimulation of the median nerve at the wrist. The various nerve conduction parameters from the affected nerves of the patients were compared with those from the clinically normal nerves of patients as well as data from healthy individuals. Analysis of the data and clinical correlation studies indicate the suitability of amplitudes of the SNAPs and CNAPs rather than the nerve conduction velocities in better characterizing the neuropathy of the patients. Significantly reduced amplitudes of responses from clinically unaffected nerves of patients indicate an early stage of neuropathy, thus being of predictive value. Further, a discriminant classifier, trained on data from clinically affected nerves of patients, classified most of the data from clinically unaffected nerves of patients as abnormal. This indicates that clinical neurophysiological studies can reveal leprous neuropathy much before it becomes clinically evident by means of sensory or motor loss. A discriminant score involving only the parameters of motor threshold, amplitude of digit potential and palm nerve conduction velocity is able to classify almost all of the normal and abnormal responses. The authors hope that further confirmative studies might ultimately lead to the use of the study of distal sensory conduction in the upper limbs in possible screening of a population exposed to Mycobacterium leprae. On the other hand, misclassification of a normal person occurred and suggests that further refinement of the methods is necessary in order to facilitate wider use of the methods under held conditions.

Changes in testicular function following specific deprivation of LH in the adult male rabbit

Sexually mature male rabbits actively immunized against highly purified ovine LH (oLH) were used as a model system to study the effects of endogenous LH deprivation (and therefore testosterone) on spermatogenesis as well as pituitary FSH secretion. Immunization against oLH generated antibody titres capable of cross-reacting and neutralizing rabbit LH and this resulted in a significant reduction (P<0.01) in serum testosterone levels by 2-4 weeks of immunization. A significant increase in circulating FSH concentration (from a basal level of similar to 1 ng to 60-100 ng/ml; P<0.01) was observed within 4-6 weeks of immunization, perhaps a consequence of the negative feedback effect of the lack of testosterone. The effect of LH deprivation on spermatogenesis assessed by DNA flow cytometry and histological analyses of testicular biopsy tissue revealed that lack of testosterone primarily results in a rapid reduction and complete absence of round (1C) and elongated (HC) spermatids. The immediate effect of LH/testosterone deprivation thus appears to be at the step of meiotic transformation of primary spermatocytes (4C) to 1C. A significant reduction (>80%; P<0.01) in the 4C population and a relative accumulation (>90%; P<0.01) in spermatogonia (2C) was also observed, suggesting a need for testosterone during the transformation of 2C to 1C. In all but one of the rabbits, both qualitative and quantitative recovery in spermatogenesis occurred during the recovery phase, even at a time when only a marginal increase in serum testosterone (compared with the preimmunization) levels was observed as a result of a rapid decline in the cross-reactive antibody titres. These results clearly show that LH/testosterone deprivation in addition to primarily affecting the meiotic step also regulates the conversion of 2C to 4C during spermatogenesis.

A genetic algorithm with characteristic amplification through multiple geographically isolated populations and varied fitness landscapes

This paper proposes a new approach, wherein multiple populations are evolved on different landscapes. The problem statement is broken down, to describe discrete characteristics. Each landscape, described by its fitness landscape is used to optimize or amplify a certain characteristic or set of characteristics. Individuals from each of these populations are kept geographically isolated from each other Each population is evolved individually. After a predetermined number of evolutions, the system of populations is analysed against a normalized fitness function. Depending on this score and a predefined merging scheme, the populations are merged, one at a time, while continuing evolution. Merging continues until only one final population remains. This population is then evolved, following which the resulting population will contain the optimal solution. The final resulting population will contain individuals which have been optimized against all characteristics as desired by the problem statement. Each individual population is optimized for a local maxima. Thus when populations are merged, the effect is to produce a new population which is closer to the global maxima.

A genetic algorithm with characteristic amplification through multiple geographically isolated populations and varied fitness landscapes

This paper proposes a new approach, wherein multiple populations are evolved on different landscapes. The problem statement is broken down, to describe discrete characteristics. Each landscape, described by its fitness landscape is used to optimize or amplify a certain characteristic or set of characteristics. Individuals from each of these populations are kept geographically isolated from each other Each population is evolved individually. After a predetermined number of evolutions, the system of populations is analysed against a normalized fitness function. Depending on this score and a predefined merging scheme, the populations are merged, one at a time, while continuing evolution. Merging continues until only one final population remains. This population is then evolved, following which the resulting population will contain the optimal solution. The final resulting population will contain individuals which have been optimized against all characteristics as desired by the problem statement. Each individual population is optimized for a local maxima. Thus when populations are merged, the effect is to produce a new population which is closer to the global maxima.

Rectilinear Path Following in 3D Space

This paper addresses the problem of determining an optimal (shortest) path in three dimensional space for a constant speed and turn-rate constrained aerial vehicle, that would enable the vehicle to converge to a rectilinear path, starting from any arbitrary initial position and orientation. Based on 3D geometry, we propose an optimal and also a suboptimal path planning approach. Unlike the existing numerical methods which are computationally intensive, this optimal geometrical method generates an optimal solution in lesser time. The suboptimal solution approach is comparatively more efficient and gives a solution that is very close to the optimal one. Due to its simplicity and low computational requirements this approach can be implemented on an aerial vehicle with constrained turn radius to reach a straight line with a prescribed orientation as required in several applications. But, if the distance between the initial point and the straight line to be followed along the vertical axis is high, then the generated path may not be flyable for an aerial vehicle with limited range of flight path angle and we resort to a numerical method for obtaining the optimal solution. The numerical method used here for simulation is based on multiple shooting and is found to be comparatively more efficient than other methods for solving such two point boundary value problem.

Recovery of tropical rainforest avifauna in relation to vegetation succession following shifting cultivation in Mizoram, north-east India

1. Recovery of rainforest bird community structure and composition, in relation to forest succession after slash-and-burn shifting cultivation or jhum was studied in Mizoram, north-east India. Replicate fallow sites abandoned after shifting cultivation 1, 5, 10, 25 and approximate to 100 years ago, were compared with primary evergreen and semi-evergreen forest using transect and quadrat sampling. 2. Vegetation variables such as woody plant species richness, tree density and vertical stratification increased with fallow age in a rapid. nun-linear, asymptotic manner. Principal components analysis of vegetation variables summarized 92.8% of the variation into two axes: PC1 reflecting forest development and woody plant succession (variables such as tree density, woody plant species richness), and PC2 depicting bamboo density, which increased from 1 to 25 years and declined thereafter. 3. Bird species richness, abundance and diversity, increased rapidly and asymptotically during succession paralleling vegetation recovery as shown by positive correlations with fallow age and PC1 scores of sites. Bamboo density reflected by PC2 had a negative effect on bird species richness and abundance. 4. The bird community similarity (Morisita index) of sites with primary forest also increased asymptotically with fallow age indicating sequential species turnover during succession. Bird community similarity of sites with primary forest (or between sites) was positively correlated with both physiognomic and floristic similarities with primary forest (or between sites). 5. The number of bird species in guilds associated with forest development and woody plants (canopy insectivores, frugivores: bark feeders) was correlated with PCI scores of the sites. Species in other guilds (e. g. granivores, understorey insectivores) appeared to dominate during early and mid-succession. 6. The non-linear relationships imply that fallow periods less than a threshold of 25 years for birds, and about 50-75 years for woody plants, are likely to cause substantial community alteration. 7. As 5-10-year rotation periods or jhum cycles prevail in many parts of north-east India. there is a need to protect and conserve tracts of late-successional and primary forest.

Model-following Neuro-adaptive approach for robust control of high performance aircrafts

Based on dynamic inversion, a relatively straightforward approach is presented in this paper for nonlinear flight control design of high performance aircrafts, which does not require the normal and lateral acceleration commands to be first transferred to body rates before computing the required control inputs. This leads to substantial improvement of the tracking response. Promising results are obtained from six degree-offreedom simulation studies of F-16 aircraft, which are found to be superior as compared to an existing approach (which is also based on dynamic inversion). The new approach has two potential benefits, namely reduced oscillatory response (including elimination of non-minimum phase behavior) and reduced control magnitude. Next, a model-following neuron-adaptive design is augmented the nominal design in order to assure robust performance in the presence of parameter inaccuracies in the model. Note that in the approach the model update takes place adaptively online and hence it is philosophically similar to indirect adaptive control. However, unlike a typical indirect adaptive control approach, there is no need to update the individual parameters explicitly. Instead the inaccuracy in the system output dynamics is captured directly and then used in modifying the control. This leads to faster adaptation, which helps in stabilizing the unstable plant quicker. The robustness study from a large number of simulations shows that the adaptive design has good amount of robustness with respect to the expected parameter inaccuracies in the model.

Propyl-2-(8-(3,4-Difluorobenzyl)-2 `,5 `-Dioxo-8-AzaspiroBicyclo3.2.1] Octane-3,4 `-Imidazolidine]-1 `-yl) Acetate Induces Apoptosis in Human Leukemia Cells through Mitochondrial Pathway following Cell Cycle Arrest

Background: Due to the functional defects in apoptosis signaling molecules or deficient activation of apoptosis pathways, leukemia has become an aggressive disease with poor prognosis. Although the majority of leukemia patients initially respond to chemotherapy, relapse is still the leading cause of death. Hence targeting apoptosis pathway would be a promising strategy for the improved treatment of leukemia. Hydantoin derivatives possess a wide range of important biological and pharmacological properties including anticancer properties. Here we investigated the antileukemic activity and mechanism of action of one of the potent azaspiro hydantoin derivative, (ASHD). Materials and Methods: To investigate the antileukemic efficacy of ASHD, we have used MTT assay, cell cycle analysis by FACS, tritiated thymidine incorporation assay, Annexin V staining, JC1 staining and western blot analysis. Results: Results showed that ASHD was approximately 3-fold more potent than the parent compounds in inducing cytotoxicity. Tritiated thymidine assay in conjunction with cell cycle analysis suggests that ASHD inhibited the growth of leukemic cells. The limited effect of ASHD on cell viability of normal cells indicated that it may be specifically directed to cancer cells. Translocation of phosphatidyl serine, activation of caspase 3, caspase 9, PARP, alteration in the ratio of BCL2/BAD protein expression as well as the loss of mitochondrial membrane potential suggests activation of the intrinsic pathway of apoptosis. Conclusion: These results could facilitate the future development of novel hydantoin derivatives as chemotherapeutic agents for leukemia.