Polymorphs, Salts, and Cocrystals: What's in a Name?

The December 2011 release of a draft United States Food and Drug Administration (FDA) guidance concerning regulatory classification of pharmaceutical cocrystals of active pharmaceutical ingredients (APIs) addressed two matters of topical interest to the crystal engineering and pharmaceutical science communities: (1) a proposed definition of cocrystals; (2) a proposed classification of pharmaceutical cocrystals as dissociable ``API-excipient'' molecular complexes. The Indo U.S. Bilateral Meeting sponsored by the Indo-U.S. Science and Technology Forum titled The Evolving Role of Solid State Chemistry in Pharmaceutical Science was held in Manesar near Delhi, India, from February 2-4, 2012. A session of the meeting was devoted to discussion of the FDA guidance draft. The debate generated strong consensus on the need to define cocrystals more broadly and to classify them like salts. It was also concluded that the diversity of API crystal forms makes it difficult to classify solid forms into three categories that are mutually exclusive. This perspective summarizes the discussion in the Indo-U.S. Bilateral Meeting and includes contributions from researchers who were not participants in the meeting.

How good are the simulations of tropical SST-rainfall relationship by IPCC AR4 atmospheric and coupled models?

The failure of atmospheric general circulation models (AGCMs) forced by prescribed SST to simulate and predict the interannual variability of Indian/Asian monsoon has been widely attributed to their inability to reproduce the actual sea surface temperature (SST)-rainfall relationship in the warm Indo-Pacific oceans. This assessment is based on a comparison of the observed and simulated correlation between the rainfall and local SST. However, the observed SSTconvection/rainfall relationship is nonlinear and for this a linear measure such as the correlation is not an appropriate measure. We show that the SST-rainfall relationship simulated by atmospheric and coupled general circulation models in IPCC AR4 is nonlinear, as observed, and realistic over the tropical West Pacific (WPO) and the Indian Ocean (IO). The SST-rainfall pattern simulated by the coupled versions of these models is rather similar to that from the corresponding atmospheric one, except for a shift of the entire pattern to colder/warmer SSTs when there is a cold/warm bias in the coupled version.

A new species of Duttaphrynus (Anura : Bufonidae) from Northeast India

A new species of montane toad Duttaphrynus is described from Nagaland state of Northeast India. The new species is diagnosable based on following combination of characters: absence of preorbital, postorbital and orbitotympanic ridges, elongated and broad parotid gland, first finger longer than second and presence of a mid-dorsal line. The tympanum is hidden under a skin fold (in male) or absent (in female). The species is compared with its congers from India and Indo-China. We propose to consider Duttaphrynus wokhaensis as junior synonym of Duttaphrynus melanostictus.

Performance evaluation of chemistry transport models over India

Using continuous and near-real time measurements of the mass concentrations of black carbon (BC) aerosols near the surface, for a period of 1 year (from January to December 2006) from a network of eight observatories spread over different environments of India, a space-time synthesis is generated. The strong seasonal variations observed, with a winter high and summer low, are attributed to the combined effects of changes in synoptic air mass types, modulated strongly by the atmospheric boundary layer dynamics. Spatial distribution shows much higher BC concentration over the Indo-Gangetic Plain (IGP) than the peninsular Indian stations. These were examined against the simulations using two chemical transport models, GOCART (Goddard Global Ozone Chemistry Aerosol Radiation and Transport) and CHIMERE for the first time over Indian region. Both the model simulations significantly deviated from the measurements at all the stations; more so during the winter and pre-monsoon seasons and over mega cities. However, the CHIMERE model simulations show better agreement compared with the measurements. Notwithstanding this, both the models captured the temporal variations; at seasonal and subseasonal timescales and the natural variabilities (intra-seasonal oscillations) fairly well, especially at the off-equatorial stations. It is hypothesized that an improvement in the atmospheric boundary layer (ABL) parameterization scheme for tropical environment might lead to better results with GOCART.

Trends in aerosol optical depth over Indian region: Potential causes and impact indicators

The first regional synthesis of long-term (back to similar to 25 years at some stations) primary data (from direct measurement) on aerosol optical depth from the ARFINET (network of aerosol observatories established under the Aerosol Radiative Forcing over India (ARFI) project of Indian Space Research Organization over Indian subcontinent) have revealed a statistically significant increasing trend with a significant seasonal variability. Examining the current values of turbidity coefficients with those reported similar to 50 years ago reveals the phenomenal nature of the increase in aerosol loading. Seasonally, the rate of increase is consistently high during the dry months (December to March) over the entire region whereas the trends are rather inconsistent and weak during the premonsoon (April to May) and summer monsoon period (June to September). The trends in the spectral variation of aerosol optical depth (AOD) reveal the significance of anthropogenic activities on the increasing trend in AOD. Examining these with climate variables such as seasonal and regional rainfall, it is seen that the dry season depicts a decreasing trend in the total number of rainy days over the Indian region. The insignificant trend in AOD observed over the Indo-Gangetic Plain, a regional hot spot of aerosols, during the premonsoon and summer monsoon season is mainly attributed to the competing effects of dust transport and wet removal of aerosols by the monsoon rain. Contributions of different aerosol chemical species to the total dust, simulated using Goddard Chemistry Aerosol Radiation and Transport model over the ARFINET stations, showed an increasing trend for all the anthropogenic components and a decreasing trend for dust, consistent with the inference deduced from trend in Angstrom exponent.

Phylogeography unplugged: comparative surveys in the genomic era

In March 2012, the authors met at the National Evolutionary Synthesis Center (NESCent) in Durham, North Carolina, USA, to discuss approaches and cooperative ventures in Indo-Pacific phylogeography. The group emerged with a series of findings: (1) Marine population structure is complex, but single locus mtDNA studies continue to provide powerful first assessment of phylogeographic patterns. (2) These patterns gain greater significance/power when resolved in a diversity of taxa. New analytical tools are emerging to address these analyses with multi-taxon approaches. (3) Genome-wide analyses are warranted if selection is indicated by surveys of standard markers. Such indicators can include discordance between genetic loci, or between genetic loci and morphology. Phylogeographic information provides a valuable context for studies of selection and adaptation. (4) Phylogeographic inferences are greatly enhanced by an understanding of the biology and ecology of study organisms. (5) Thorough, range-wide sampling of taxa is the foundation for robust phylogeographic inference. (6) Congruent geographic and taxonomic sampling by the Indo-Pacific community of scientists would facilitate better comparative analyses. The group concluded that at this stage of technology and software development, judicious rather than wholesale application of genomics appears to be the most robust course for marine phylogeographic studies. Therefore, our group intends to affirm the value of traditional (''unplugged'') approaches, such as those based on mtDNA sequencing and microsatellites, along with essential field studies, in an era with increasing emphasis on genomic approaches.

The April 2012 Indian Ocean earthquakes: Seismotectonic context and implications for their mechanisms

The 11 April 2012 earthquakes (M-w 8.6 and M-w 8.2) were sourced within the Northern Wharton Basin in the northeastern part of the Indo-Australian diffuse plate boundary. This unusually active oceanic intraplate region has generated many large earthquakes in the past, most of which are believed to have occurred by strike-slip motion, triggered by the NW-SE oriented compressional stresses acting across the Indian and Australian plates. In the aftermath of the 2004 megathrust earthquake along the nearby Sunda Trench, increased seismicity in the Northern Wharton Basin is attributed to the stress transfer from the Sumatra-Andaman plate boundary. Models proposed for the April 2012 earthquakes differ somewhat in details but partly attribute their complex rupture to the reactivation of pre-existing structures. These structures include previously mapped N-S trending fracture zones within the Northern Wharton Basin and E-W lineations across the Ninetyeast Ridge. In this paper, we review the regional tectonics and past seismicity on the Indo-Australian Plate in order to understand the seismotectonic setting of the April 2012 Indian Ocean earthquakes. (c) 2014 Elsevier B.V. All rights reserved.

Sensitivity of meteorological input and soil properties in simulating aerosols (dust, PM10, and BC) using CHIMERE chemistry transport model

The objective of this study is to evaluate the ability of a European chemistry transport model, `CHIMERE' driven by the US meteorological model MM5, in simulating aerosol concentrations dust, PM10 and black carbon (BC)] over the Indian region. An evaluation of a meteorological event (dust storm); impact of change in soil-related parameters and meteorological input grid resolution on these aerosol concentrations has been performed. Dust storm simulation over Indo-Gangetic basin indicates ability of the model to capture dust storm events. Measured (AERONET data) and simulated parameters such as aerosol optical depth (AOD) and Angstrom exponent are used to evaluate the performance of the model to capture the dust storm event. A sensitivity study is performed to investigate the impact of change in soil characteristics (thickness of the soil layer in contact with air, volumetric water, and air content of the soil) and meteorological input grid resolution on the aerosol (dust, PM10, BC) distribution. Results show that soil parameters and meteorological input grid resolution have an important impact on spatial distribution of aerosol (dust, PM10, BC) concentrations.

Insights into Himalayan biogeography from geckos: A molecular phylogeny of Cyrtodactylus (Squamata: Gekkonidae)

The India-Asia collision profoundly influenced the climate, topography and biodiversity of Asia, causing the formation of the biodiverse Himalayas. The species-rich gekkonid genus Cyrtodactylus is an ideal clade for exploring the biological impacts of the India-Asia collision, as previous phylogenetic hypotheses suggest basal divergences occurred within the Himalayas and Indo-Burma during the Eocene. To this end, we sampled for Cyrtodactylus across Indian areas of the Himalayas and Indo-Burma Hotspots and used three genes to reconstruct relationships and estimate divergence times. Basal divergences in Cyrtodactylus, Hemidactylus and the Palaearctic naked-toed geckos were simultaneous with or just preceded the start of the India-Asia collision. Diversification within Cyrtodactylus tracks the India-Asia collision and subsequent geological events. A number of geographically concordant clades are resolved within Indo-Burmese Cyrtodactylus. Our study reveals 17 divergent lineages that may represent undescribed species, underscoring the previously undocumented diversity of the region. The importance of rocky habitats for Cyrtodactylus indicates the Indo-Gangetic flood plains and the Garo-Rajmahal Gap are likely to have been important historical barriers for this group. (C) 2014 Elsevier Inc. All rights reserved.

An assessment of terrestrial water storage, rainfall and river discharge over Northern India from satellite data

Terrestrial water storage (TWS) plays a key role in the global water cycle and is highly influenced by climate variability and human activities. In this study, monthly TWS, rainfall and Ganga-Brahmaputra river discharge (GBRD) are analysed over India for the period of 2003-12 using remote sensing satellite data. The spatial pattern of mean TWS shows a decrease over a large and populous region of Northern India comprising the foothills of the Himalayas, the Indo-Gangetic Plains and North East India. Over this region, the mean monthly TWS exhibits a pronounced seasonal cycle and a large interannual variability, highly correlated with rainfall and GBRD variations (r > 0.8) with a lag time of 2 months and 1 month respectively. The time series of monthly TWS shows a consistent and statistically significant decrease of about 1 cm year(-1) over Northern India, which is not associated with changes in rainfall and GBRD. This recent change in TWS suggests a possible impact of rapid industrialization, urbanization and increase in population on land water resources. Our analysis highlights the potential of the Earth-observation satellite data for hydrological applications.

Optical properties and CCN activity of aerosols in a high-altitude Himalayan environment: Results from RAWEX-GVAX

The seasonality and mutual dependence of aerosol optical properties and cloud condensation nuclei (CCN) activity under varying meteorological conditions at the high-altitude Nainital site (2km) in the Indo-Gangetic Plains were examined using nearly year-round measurements (June 2011 to March 2012) at the Atmospheric Radiation Measurement mobile facility as part of the Regional Aerosol Warming Experiment-Ganges Valley Aerosol Experiment of the Indian Space Research Organization and the U.S. Department of Energy. The results from collocated measurements provided enhanced aerosol scattering and absorption coefficients, CCN concentrations, and total condensation nuclei concentrations during the dry autumn and winter months. The CCN concentration (at a supersaturation of 0.46) was higher during the periods of high aerosol absorption (single scattering albedo (SSA)<0.80) than during the periods of high aerosol scattering (SSA>0.85), indicating that the aerosol composition seasonally changes and influences the CCN activity. The monthly mean CCN activation ratio (at a supersaturation of 0.46) was highest (>0.7) in late autumn (November); this finding is attributed to the contribution of biomass-burning aerosols to CCN formation at high supersaturation conditions.

An estimate of the number of tropical tree species

The high species richness of tropical forests has long been recognized, yet there remains substantial uncertainty regarding the actual number of tropical tree species. Using a pantropical tree inventory database from closed canopy forests, consisting of 657,630 trees belonging to 11,371 species, we use a fitted value of Fisher's alpha and an approximate pantropical stem total to estimate the minimum number of tropical forest tree species to fall between similar to 40,000 and similar to 53,000, i.e., at the high end of previous estimates. Contrary to common assumption, the Indo-Pacific region was found to be as species-rich as the Neotropics, with both regions having a minimum of similar to 19,000-25,000 tree species. Continental Africa is relatively depauperate with a minimum of similar to 4,500-6,000 tree species. Very few species are shared among the African, American, and the Indo-Pacific regions. We provide a methodological framework for estimating species richness in trees that may help refine species richness estimates of tree-dependent taxa.

Performance of WRF-Chem over Indian region: Comparison with measurements

The aerosol mass concentrations over several Indian regions have been simulated using the online chemistry transport model, WRF-Chem, for two distinct seasons of 2011, representing the pre-monsoon (May) and post-monsoon (October) periods during the Indo-US joint experiment `Ganges Valley Aerosol Experiment (GVAX)'. The simulated values were compared with concurrent measurements. It is found that the model systematically underestimates near-surface BC mass concentrations as well as columnar Aerosol Optical Depths (AODs) from the measurements. Examining this in the light of the model-simulated meteorological parameters, we notice the model overestimates both planetary boundary layer height (PBLH) and surface wind speeds, leading to deeper mixing and dispersion and hence lower surface concentrations of aerosols. Shortcoming in simulating rainfall pattern also has an impact through the scavenging effect. It also appears that the columnar AODs are influenced by the unrealistic emission scenarios in the model. Comparison with vertical profiles of BC obtained from aircraft-based measurements also shows a systematic underestimation by the model at all levels. It is seen that concentration of other aerosols, viz., dust and sea-salt are closely linked with meteorological conditions prevailing over the region. Dust is higher during pre-monsoon periods due to the prevalence of north-westerly winds that advect dust from deserts of west Asia into the Indo-Gangetic plain. Winds and rainfall influence sea-salt concentrations. Thus, the unrealistic simulation of wind and rainfall leads to model simulated dust and sea-salt also to deviate from the real values; which together with BC also causes underperformance of the model with regard to columnar AOD. It appears that for better simulations of aerosols over Indian region, the model needs an improvement in the simulation of the meteorology.

A novel gene THSD7A is associated with obesity

Body mass index (BMI) is a non-invasive measurement of obesity. It is commonly used for assessing adiposity and obesity-related risk prediction. Genetic differences between ethnic groups are important factors, which contribute to the variation in phenotypic effects. India inhabited by the first out-of-Africa human population and the contemporary Indian populations are admixture of two ancestral populations; ancestral north Indians (ANI) and ancestral south Indians (ASI). Although ANI are related to Europeans, ASI are not related to any group outside Indian-subcontinent. Hence, we expect novel genetic loci associated with BMI. In association analysis, we found eight genic SNPs in extreme of distribution (P <= 3.75 x 10(-5)), of which WWOX has already been reported to be associated with obesity-related traits hence excluded from further study. Interestingly, we observed rs1526538, an intronic SNP of THSD7A; a novel gene significantly associated with obesity (P = 2.88 x 10(-5), 8.922 x 10(-6) and 2.504 x 10(-9) in discovery, replication and combined stages, respectively). THSD7A is neural N-glycoprotein, which promotes angiogenesis and it is well known that angiogenesis modulates obesity, adipose metabolism and insulin sensitivity, hence our result find a correlation. This information can be used for drug target, early diagnosis of obesity and treatment.

Establecimiento y micropropagación in vitro de germoplasma de níspero (Manilkara zapota L) colectado en Nicaragua

Se establecieron una serie de ensayos preliminares y un ensayo definitivo con el propósito de lograr establecer en condiciones in vitro embriones cigóticos de semillas de frutas maduras e inmaduras de níspero (Manilkara zapota L). En los ensayos preliminares se trató de lograr la germinación de la semilla y el desarrollo de plántulas en diferentes condiciones: platos petri con papel filtro y agua destilada estéril, medio de cultivo líquido con y sin reguladores de crecimiento; y con y sin tela de venda como nodriza. El ensayo definitivo constó de dos fases: A) Establecimiento in vitro de nispero a partir de embriones cigóticos de semillas de frutas en sus dos estados de madurez (inmaduros-maduros), en trece variantes del medio de cultivo básico MS (1962), suplementado con diversas concentraciones y combinaciones de los reguladores de crecimiento ANA (Ácido Naftalen Acético), ffiA (Ácido Indo! Butírico), CA (Carbón activado), GA3 (Ácido Giberélico). B) La micropropagación de níspero en cuatro variantes del medio de cultivo MS (1962) a partir de trozos de tallos conteniendo yemas axilares de las plantas desarrolladas en la fase A de este ensayo. En ambos ensayos se utilizaron 20 repeticiones por tratamiento. Se logró obtener la germinación de semilla de nispero en ensayos de laboratorio en platos petri con papel filtro y agua destilada estéril, en tubos de ensayos conteniendo medio de cultivo líquido, el cual facilita la imbibición de la semilla pero puede causar afixia. En el establecimiento de los explantes la contaminación causada por hongos y bacterias fue inferior en los medios de cultivo conteniendo embriones cigóticos provenientes de frutas inmaduras. Las mayores alturas promedio por plantas se presentaron en los embriones provenientes de frutas maduras; las mismas alcanzaron el estadio de desarrollo número III (plantas formadas con las primeras hojas verdaderas y raíz), por el contrario las mayores longitudes promedios de raíces por plantas se obtuvieron en plantas desarrolladas a partir de embriones cigóticos provenientes de frutas inmaduras. El medio de cultivo 6 (MS + 2 mg/l de IBA) indujo los mejores resultados en altura y longitud promedio de raíces de plantas provenientes de ambos estados de madurez de la fruta. La micropropagación de plántulas a partir de trozos de tallos con yemas axilares no fue posible debido a que los explantes no lograron desarrollar raíces, aunque sí presentaron primordios foliares desarrollados.