Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors

N-Myristoyltransferase (NMT) represents a promising drug target for human African trypanosomiasis (HAT), which is caused by the parasitic protozoa Trypanosoma brucei. We report the optimization of a high throughput screening hit (1) to give a lead molecule DDD85646 (63), which has potent activity against the enzyme (IC50 = 2 nM) and T. brucei (EC50 = 2 nM) in culture. The compound has good oral pharmacokinetics and cures rodent models of peripheral HAT infection. This compound provides an excellent tool for validation of T. brucei NMT as a drug target for HAT as well as a valuable lead for further optimization.</p

On the selection and design of proteins and peptide derivatives for the production of photoluminescent, red-emitting gold quantum clusters

Novel pathways of the synthesis of photoluminescent gold quantum clusters (AuQCs) using biomolecules as reactants provide biocompatible products for biological imaging techniques. In order to rationalize the rules for the preparation of red-emitting AuQCs in aqueous phase using proteins or peptides, the role of different organic structural units was investigated. Three systems were studied: proteins, peptides, and amino acid mixtures, respectively. We have found that cysteine and tyrosine are indispensable residues. The SH/S-S ratio in a single molecule is not a critical factor in the synthesis, but on the other hand, the stoichiometry of cysteine residues and the gold precursor is crucial. These observations indicate the importance of proper chemical behavior of all species in a wide size range extending from the atomic distances (in the AuI-S semi ring) to nanometer distances covering the larger sizes of proteins assuring the hierarchical structure of the whole self-assembled system

Sequential application of hyperspectral indices for delineation of stripe rust infection and nitrogen deficiency in wheat

© 2015, Springer Science+Business Media New York. Nitrogen (N) fertilization is crucial for the growth and development of wheat crops, and yet increased use of N can also result in increased stripe rust severity. Stripe rust infection and N deficiency both cause changes in foliar physiological activity and reduction in plant pigments that result in chlorosis. Furthermore, stripe rust produce pustules on the leaf surface which similar to chlorotic regions have a yellow color. Quantifying the severity of each factor is critical for adopting appropriate management practices. Eleven widely-used vegetation indices, based on mathematic combinations of narrow-band optical reflectance measurements in the visible/near infrared wavelength range were evaluated for their ability to discriminate and quantify stripe rust severity and N deficiency in a rust-susceptible wheat variety (H45) under varying conditions of nitrogen status. The physiological reflectance index (PhRI) and leaf and canopy chlorophyll index (LCCI) provided the strongest correlation with levels of rust infection and N-deficiency, respectively. When PhRI and LCCI were used in a sequence, both N deficiency and rust infection levels were correctly classified in 82.5 and 55 % of the plots at Zadoks growth stage 47 and 75, respectively. In misclassified plots, an overestimation of N deficiency was accompanied by an underestimation of the rust infection level or vice versa. In 18 % of the plots, there was a tendency to underestimate the severity of stripe rust infection even though the N-deficiency level was correctly predicted. The contrasting responses of the PhRI and LCCI to stripe rust infection and N deficiency, respectively, and the relative insensitivity of these indices to the other parameter makes their use in combination suitable for quantifying levels of stripe rust infection and N deficiency in wheat crops under field conditions

Characterization and Evaluation of a Rare Orchid Renanthera imschootiana Rolfe from Manipur & Nagaland

The orchid Renanthera imschootiana Rolfe is the only species under the genus available in India at Manipur and Nagaland, which is a part of Indo-Burma mega diversity hot-spot. The only collection, NRCO-Coll-77 (1998)/IC 566525 of this species available with us was evaluated and characterized as per 'Common Descriptors of Orchids' developed at this center. Monopodial nature in habit, un-branched raceme with a length of 32.2 cm having attractive dominant red-purple (RHS-60A) flowers and petals coloured grayed orange (RHS-164C) with shade is typical of this species. Broad, lateral sepals with attractive dominant crimson/red purple colour flower having medium-range vase life of 23.7 days, imparts high breeding value to this species for developing new hybrid derivatives

Ocular Manifestations in Human Immunodeficiency Virus

The Human Immunodeficiency Virus (HIV) disease is a serious pandemic condition condition which affects all the the organs of the body. Ocular manifestations occoccur mostly during the late phase of the infection. The hallmark of thee disease is a decrease in the number of CD4+ T cells. The pThe patients are asymptomatic during the initial phases, followed by minimal symptoms like fever, weight loss, and oral thrush. The reduction in CD4+T cell level is directly proportionatete to the symptoms and severity of the disease. HIV infection is more common among sex workers and, drug abusers. 7070% of HIV-1 infections are due to heterosexual transmission. There is increased incidence of HIV infectionss in women, which translates to the the increased maternal- infant infection. The pThe patients with HIV infection remain asymptomatic during the early phase because of which of which its goes unnoticed. The aThe acute viral syndrome develops 2 to&nbsp; to 4 weeks after the 1st exposure, the incubation period being 6 days to 6 weeks. The symptoms range fromrange from fever, myalgia, fatigue, headache, and weight loss. These symptoms lasted from 3 to 25 days. This article targets the manifestation of HIV in the eye for afor a better understanding ofing of the severity and progression of the disease. The ocular manifestations are seenseen in 82.6% of HIV infected patients. These manifestations are related to cell- mediated immunity, leading to risk of infection with bacteria, fungi, virus, and parasites and its incidence is different in children and adult. Children are found to are found to have lower incidence of retinitis but higher incidence of keratoconjunctivitis sicca. The immune status and CD4 cell count demonstratess various ocular complications in HIV patients. CD4 cell count of 500 leads to Kaposi’s sarcoma, lymphoma, and tuberculosis. A CD4 cell count less than 250 leads to Pneumocystosis, Retinal microvasculopathy, toxoplasmosis and CD4 cell count less than 100 causess KKeratoconjunctivitis sicca and retinitis. These These HIV&nbsp; infected patients may present only with only ocular symptoms. Early and prompt and prompt diagnosis can aid in aggressive treatment and better prognosis of the disease. The the HIV&nbsp; infected patients should be undergo thorough anterior segment examination byby Slit slit-lamp biomicroscopy and dilated fundus examination to rule out posterior segment pathology

In situ approach for rapid characterization to aid on farm conservation of coconut germplasm - A case study of two ecotypes from West coast of India

Characterization and evaluation of coconut germplasm have conventionally been undertaken in ex situ gene banks, which take a minimum duration of fifteen years. On the other hand, utilization of coconut populations in situ can effectively reduce the time required for characterization of the populations. Hence, a concept to make a paradigm shift in the existing approach of coconut germplasm characterization is advocated in this study with a view to broaden the conservation base and facilitate inclusion of identified diverse ecotypes. The methodology has been applied to identify, locate and characterize two tall coconut ecotypes viz., Bedakam and Kuttiyadi, from northern Kerala. Agronomic traits, viz., higher number of nuts per palm, higher copra content and better performance under marginal management conditions along with adaptation to the environment, were the major reasons for preference of these ecotypes among the farmers. Comparison of the two ecotypes revealed that the traits, trunk girth, length of internode, number of leaves, number of bunches with nuts, number of nuts, shell weight, husked fruit weight and fruit weight were higher in Kuttiyadi than in Bedakam ecotype. On the other hand, number of leaf scars per meter, length of inflorescence, fruit breadth, husk weight, nut cavity volume and copra weight were higher in Bedakam compared to Kuttiyadi ecotype. Relevance, utility and importance of the study are discussed from the perspective of effective utilization of the coconut diversity in situ and their possible further use in coconut improvement efforts through conservation strategies

In situ approach for rapid characterization to aid on farm conservation of coconut germplasm - A case study of two ecotypes from West coast of India

Characterization and evaluation of coconut germplasm have conventionally been undertaken in ex situ gene banks, which take a minimum duration of fifteen years. On the other hand, utilization of coconut populations in situ can effectively reduce the time required for characterization of the populations. Hence, a concept to make a paradigm shift in the existing approach of coconut germplasm characterization is advocated in this study with a view to broaden the conservation base and facilitate inclusion of identified diverse ecotypes. The methodology has been applied to identify, locate and characterize two tall coconut ecotypes viz., Bedakam and Kuttiyadi, from northern Kerala. Agronomic traits, viz., higher number of nuts per palm, higher copra content and better performance under marginal management conditions along with adaptation to the environment, were the major reasons for preference of these ecotypes among the farmers. Comparison of the two ecotypes revealed that the traits, trunk girth, length of internode, number of leaves, number of bunches with nuts, number of nuts, shell weight, husked fruit weight and fruit weight were higher in Kuttiyadi than in Bedakam ecotype. On the other hand, number of leaf scars per meter, length of inflorescence, fruit breadth, husk weight, nut cavity volume and copra weight were higher in Bedakam compared to Kuttiyadi ecotype. Relevance, utility and importance of the study are discussed from the perspective of effective utilization of the coconut diversity in situ and their possible further use in coconut improvement efforts through conservation strategies

Custom Integrated Circuits

Contains table of contents for Part III, table of contents for Section 1 and reports on eleven research projects.IBM CorporationMIT School of EngineeringNational Science Foundation Grant MIP 94-23221Defense Advanced Research Projects Agency/U.S. Army Intelligence Center Contract DABT63-94-C-0053Mitsubishi CorporationNational Science Foundation Young Investigator Award Fellowship MIP 92-58376Joint Industry Program on Offshore Structure AnalysisAnalog DevicesDefense Advanced Research Projects AgencyCadence Design SystemsMAFET ConsortiumConsortium for Superconducting ElectronicsNational Defense Science and Engineering Graduate FellowshipDigital Equipment CorporationMIT Lincoln LaboratorySemiconductor Research CorporationMultiuniversity Research IntiativeNational Science Foundatio

Custom Integrated Circuits

Contains reports on nine research projects.Analog Devices, Inc.International Business Machines CorporationJoint Services Electronics Program Contract DAAL03-89-C-0001U.S. Air Force - Office of Scientific Research Contract AFOSR 86-0164BDuPont CorporationNational Science Foundation Grant MIP 88-14612U.S. Navy - Office of Naval Research Contract N00014-87-K-0825American Telephone and TelegraphDigital Equipment CorporationNational Science Foundation Grant MIP 88-5876