Potential source identification for aerosol concentrations over a site in Northwestern India

The collocated measurements of aerosols size distribution (ASD) and aerosol optical thickness (AOT) are analyzed simultaneously using Grimm aerosol spectrometer and MICROTOP II Sunphotometer over Jaipur, capital of Rajasthan in India. The contrast temperature characteristics during winter and summer seasons of year 2011 are investigated in the present study. The total aerosol number concentration (TANC, 0.3-20 mu m) during winter season was observed higher than in summer time and it was dominated by fine aerosol number concentration (FANC < 2 mu m). Particles smaller than 0.8 mu m (at aerodynamic size) constitute similar to 99% of all particles in winter and similar to 90% of particles in summer season. However, particles greater than 2 mu m contribute similar to 3% and similar to 0.2% in summer and winter seasons respectively. The aerosols optical thickness shows nearly similar AOT values during summer and winter but corresponding low Angstrom Exponent (AE) values during summer than winter, respectively. In this work, Potential Source Contribution Function (PSCF) analysis is applied to identify locations of sources that influenced concentrations of aerosols over study area in two different seasons. PSCF analysis shows that the dust particles from That Desert contribute significantly to the coarse aerosol number concentration (CANC). Higher values of the PSCF in north from Jaipur showed the industrial areas in northern India to be the likely sources of fine particles. The variation in size distribution of aerosols during two seasons is clearly reflected in the log normal size distribution curves. The log normal size distribution curves reveals that the particle size less than 0.8 pm is the key contributor in winter for higher ANC. (C) 2015 Elsevier B.V. All rights reserved.

Enhanced Metastatic Potential in a 3D Tissue Scaffold toward a Comprehensive in Vitro Model for Breast Cancer Metastasis

Metastasis is clinically the most challenging and lethal aspect of breast cancer. While animal-based xenograft models are expensive and time-consuming, conventional two-dimensional (2D) cell culture systems fail to mimic in vivo signaling. In this study we have developed a three-dimensional (3D) scaffold system that better mimics the topography and mechanical properties of the breast tumor, thus recreating the tumor microenvironment in vitro to study breast cancer metastasis. Porous poly(e-caprolactone) (PCL) scaffolds of modulus 7.0 +/- 0.5 kPa, comparable to that of breast tumor tissue were fabricated, on which MDA-MB-231 cells proliferated forming tumoroids. A comparative gene expression analysis revealed that cells growing in the scaffolds expressed increased levels of genes implicated in the three major events of metastasis, viz., initiation, progression, and the site-specific colonization compared to cells grown in conventional 2D tissue culture polystyrene (TCPS) dishes. The cells cultured in scaffolds showed increased invasiveness and sphere efficiency in vitro and increased lung metastasis in vivo. A global gene expression analysis revealed a significant increase in the expression of genes involved in cell cell and cell matrix interactions and tissue remodeling, cancer inflammation, and the PI3K/Akt, Wnt, NF-kappaB, and HIFI signaling pathways all of which are implicated in metastasis. Thus, culturing breast cancer cells in 3D scaffolds that mimic the in vivo tumor-like microenvironment enhances their metastatic potential. This system could serve as a comprehensive in vitro model to investigate the manifold mechanisms of breast cancer metastasis.

Measuring the magnetic-field-dependent chemical potential of a low-density three-dimensional electron gas in n-GaAs and extracting its magnetic susceptibility

We report the magnetic-field-dependent shift of the electron chemical potential in bulk, n-type GaAs at room temperature. A transient voltage of similar to 100 mu V was measured across a Au-Al2O3-GaAs metal-oxide-semiconductor capacitor in a pulsed magnetic field of similar to 6 T. Several spurious voltages larger than the signal that had plagued earlier researchers performing similar experiments were carefully eliminated. The itinerant magnetic susceptibility of GaAs is extracted from the experimentally measured data for four different doping densities, including one as low as 5 x 10(15) cm(-3). Though the susceptibility in GaAs is dominated by Landau-Peierls diamagnetism, the experimental technique demonstrated can be a powerful tool for extracting the total free carrier magnetization of any electron system. The method is also virtually independent of the carrier concentration and is expected to work better in the nondegenerate limit. Such experiments had been successfully performed in two-dimensional electron gases at cryogenic temperatures. However, an unambiguous report on having observed this effect in any three-dimensional electron gas has been lacking. We highlight the 50 year old literature of various trials and discuss the key details of our experiment that were essential for its success. The technique can be used to unambiguously yield only the itinerant part of the magnetic susceptibility of complex materials such as magnetic semiconductors and hexaborides, and thus shed light on the origin of ferromagnetism in such systems.

First-in-Class Inhibitors of Sulfur Metabolism with Bactericidal Activity against Non-Replicating M-tuberculosis

Development of effective therapies to eradicate persistent, slowly replicating M. tuberculosis (Mtb) represents a significant challenge to controlling the global TB epidemic. To develop such therapies, it is imperative to translate information from metabolome and proteome adaptations of persistent Mtb into the drug discovery screening platforms. To this end, reductive sulfur metabolism is genetically and pharmacologically implicated in survival, pathogenesis, and redox homeostasis of persistent Mtb. Therefore, inhibitors of this pathway are expected to serve as powerful tools in its preclinical and clinical validation as a therapeutic target for eradicating persisters. Here, we establish a first functional HTS platform for identification of APS reductase (APSR) inhibitors, a critical enzyme in the assimilation of sulfate for the biosynthesis of cysteine and other essential sulfur-containing molecules. Our HTS campaign involving 38?350 compounds led to the discovery of three distinct structural classes of APSR inhibitors. A class of bioactive compounds with known pharmacology displayed potent bactericidal activity in wild-type Mtb as well as MDR and XDR clinical isolates. Top compounds showed markedly diminished potency in a conditional Delta APSR mutant, which could be restored by complementation with Mtb APSR. Furthermore, ITC studies on representative compounds provided evidence for direct engagement of the APSR target. Finally, potent APSR inhibitors significantly decreased the cellular levels of key reduced sulfur-containing metabolites and also induced an oxidative shift in mycothiol redox potential of live Mtb, thus providing functional validation of our screening data. In summary, we have identified first-in-class inhibitors of APSR that can serve as molecular probes in unraveling the links between Mtb persistence, antibiotic tolerance, and sulfate assimilation, in addition to their potential therapeutic value.

Mycobacterium tuberculosis WhiB3 Responds to Vacuolar pH-induced Changes in Mycothiol Redox Potential to Modulate Phagosomal Maturation and Virulence.

The ability of Mycobacterium tuberculosis to resist intraphagosomal stresses, such as oxygen radicals and low pH, is critical for its persistence. Here, we show that a cytoplasmic redox sensor, WhiB3, and the major M. tuberculosis thiol, mycothiol (MSH), are required to resist acidic stress during infection. WhiB3 regulates the expression of genes involved in lipid anabolism, secretion, and redox metabolism, in response to acidic pH. Furthermore, inactivation of the MSH pathway subverted the expression of whiB3 along with other pH-specific genes in M. tuberculosis. Using a genetic biosensor of mycothiol redox potential (E-MSH), we demonstrated that a modest decrease in phagosomal pH is sufficient to generate redox heterogeneity in E-MSH of the M. tuberculosis population in a WhiB3-dependent manner. Data indicate that M. tuberculosis needs low pH as a signal to alter cytoplasmic E-MSH, which activates WhiB3-mediated gene expression and acid resistance. Importantly, WhiB3 regulates intraphagosomal pH by down-regulating the expression of innate immune genes and blocking phagosomal maturation. We show that this block in phagosomal maturation is in part due to WhiB3-dependent production of polyketide lipids. Consistent with these observations, Mtb Delta whiB3 displayed intramacrophage survival defect, which can be rescued by pharmacological inhibition of phagosomal acidification. Last, Mtb Delta whiB3 displayed marked attenuation in the lungs of guinea pigs. Altogether, our study revealed an intimate link between vacuolar acidification, redox physiology, and virulence in M. tuberculosis and discovered WhiB3 as crucial mediator of phagosomal maturation arrest and acid resistance in M. tuberculosis.

Stalagmite growth perturbations from the Kumaun Himalaya as potential earthquake recorders

The central part of the Himalaya (Kumaun and Garhwal Provinces of India) is noted for its prolonged seismic quiescence, and therefore, developing a longer-term time series of past earthquakes to understand their recurrence pattern in this segment assumes importance. In addition to direct observations of offsets in stratigraphic exposures or other proxies like paleoliquefaction, deformation preserved within stalagmites (speleothems) in karst system can be analyzed to obtain continuous millennial scale time series of earthquakes. The Central Indian Himalaya hosts natural caves between major active thrusts forming potential storehouses for paleoseismological records. Here, we present results from the limestone caves in the Kumaun Himalaya and discuss the implications of growth perturbations identified in the stalagmites as possible earthquake recorders. This article focuses on three stalagmites from the Dharamjali Cave located in the eastern Kumaun Himalaya, although two other caves, one of them located in the foothills, were also examined for their suitability. The growth anomalies in stalagmites include abrupt tilting or rotation of growth axes, growth termination, and breakage followed by regrowth. The U-Th age data from three specimens allow us to constrain the intervals of growth anomalies, and these were dated at 4273 +/- 410 years BP (2673-1853 BC), 2782 +/- 79 years BP (851-693 BC), 2498 +/- 117 years BP (605-371 BC), 1503 +/- 245 years BP (262-752 AD), 1346 +/- 101 years BP (563-765 AD), and 687 +/- 147 years BP (1176-1470 AD). The dates may correspond to the timings of major/great earthquakes in the region and the youngest event (1176-1470 AD) shows chronological correspondence with either one of the great medieval earthquakes (1050-1250 and 1259-1433 AD) evident from trench excavations across the Himalayan Frontal Thrust.

Spatio-temporal Map Formation Based on a Potential Function

We revisit the problem of temporal self organization using activity diffusion based on the neural gas (NGAS) algorithm. Using a potential function formulation motivated by a spatio-temporal metric, we derive an adaptation rule for dynamic vector quantization of data. Simulations results show that our algorithm learns the input distribution and time correlation much faster compared to the static neural gas method over the same data sequence under similar training conditions.

Tetraphenylethene-Based Conjugated Fluoranthene: A Potential Fluorescent Probe for Detection of Nitroaromatic Compounds

This study reports the synthesis and photophysical properties of a star-shaped, novel, fluoranthene-tetraphenylethene (TFPE) conjugated luminogen, which exhibits aggregation-induced blue-shifted emission (AIBSE). The bulky fluoranthene units at the periphery prevent intramolecular rotation (IMR) of phenyl rings and induces a blueshift with enhanced emission. The AIBSE phenomenon was investigated by solvatochromic and temperature-dependent emission studies. Nanoaggregates of TFPE, formed by varying the water/THF ratio, were investigated by SEM and TEM and correlated with optical properties. The TFPE conjugate was found to be a promising fluorescent probe towards the detection of nitroaromatic compounds (NACs), especially for 2,4,6-trinitrophenol (PA) with high sensitivity and a high Stern-Volmer quenching constant. The study reveals that nanoaggregates of TFPE formed at 30 and 70% water in THF showed unprecedented sensitivity with detection limits of 0.8 and 0.5ppb, respectively. The nanoaggregates formed at water fractions of 30 and 70% exhibit high Stern-Volmer constants (K-sv=79998 and 51120m(-1), respectively) towards PA. Fluorescence quenching is ascribed to photoinduced electron transfer between TFPE and NACs with a static quenching mechanism. Test strips coated with TFPE luminogen demonstrate fast and ultra-low-level detection of PA for real-time field analysis.

Comparative studies of AOT and NaDEHP by fluorescence technique and z-potential (ζ) measurements

The aggregation behaviors of two surfactants with the same hydrophobic tail, sodium bis(2-ethylhexyl)sulfosuccinate (AOT) and sodium bis(2-ethylhexyl)phosphate (NaDEHP), have been investigated by the fluorescence technique and z-potential (ζ) measurements. Five fine peaks of the pyrene molecule fluorescence spectroscopy appear in the surfactant solution, and the micropolarity at which pyrene locates is monitored from the intensity ratio of the first (I1) and the third peak (I3). A wide peak around 475 nm, the emission spectra of the excimer of pyrene molecules, is observed in the NaDEHP solution, while this is not found for the AOT system. The value of I1/I3 decreases in a more limited concentration range for the AOT system than for NaDEHP, indicating that small aggregates can be more easily formed by NaDEHP molecules. The z-potential results for the aggregates formed by the two surfactants show that the interaction between AOT and PVP is stronger than that between NaDEHP and PVP.

Toxicity and imaging of multi-walled carbon nanotubes in human macrophage cells.

Multi-walled carbon nanotubes (MWNTs) have been proposed for use in many applications and concerns about their potential effect on human health have led to the interest in understanding the interactions between MWNTs and human cells. One important technique is the visualisation of the intracellular distribution of MWNTs. We exposed human macrophage cells to unpurified MWNTs and found that a decrease in cell viability was correlated with uptake of MWNTs due to mainly necrosis. Cells treated with purified MWNTs and the main contaminant Fe(2)O(3) itself yielded toxicity only from the nanotubes and not from the Fe(2)O(3). We used 3-D dark-field scanning transmission electron microscopy (DF-STEM) tomography of freeze-dried whole cells as well as confocal and scanning electron microscopy (SEM) to image the cellular uptake and distribution of unpurified MWNTs. We observed that unpurified MWNTs entered the cell both actively and passively frequently inserting through the plasma membrane into the cytoplasm and the nucleus. These suggest that MWNTs may cause incomplete phagocytosis or mechanically pierce through the plasma membrane and result in oxidative stress and cell death.

The environmental and economic sustainability of potential bioethanol from willow in the UK.

Life cycle assessment has been used to investigate the environmental and economic sustainability of a potential operation in the UK in which bioethanol is produced from the hydrolysis and subsequent fermentation of coppice willow. If the willow were grown on idle arable land in the UK, or, indeed, in Eastern Europe and imported as wood chips into the UK, it was found that savings of greenhouse gas emissions of 70-90%, when compared to fossil-derived gasoline on an energy basis, would be possible. The process would be energetically self-sufficient, as the co-products, e.g. lignin and unfermented sugars, could be used to produce the process heat and electricity, with surplus electricity being exported to the National Grid. Despite the environmental benefits, the economic viability is doubtful at present. However, the cost of production could be reduced significantly if the willow were altered by breeding to improve its suitability for hydrolysis and fermentation.

Absence of branches from xylan in Arabidopsis gux mutants reveals potential for simplification of lignocellulosic biomass.

As one of the most abundant polysaccharides on Earth, xylan will provide more than a third of the sugars for lignocellulosic biofuel production when using grass or hardwood feedstocks. Xylan is characterized by a linear β(1,4)-linked backbone of xylosyl residues substituted by glucuronic acid, 4-O-methylglucuronic acid or arabinose, depending on plant species and cell types. The biological role of these decorations is unclear, but they have a major influence on the properties of the polysaccharide. Despite the recent isolation of several mutants with reduced backbone, the mechanisms of xylan synthesis and substitution are unclear. We identified two Golgi-localized putative glycosyltransferases, GlucUronic acid substitution of Xylan (GUX)-1 and GUX2 that are required for the addition of both glucuronic acid and 4-O-methylglucuronic acid branches to xylan in Arabidopsis stem cell walls. The gux1 gux2 double mutants show loss of xylan glucuronyltransferase activity and lack almost all detectable xylan substitution. Unexpectedly, they show no change in xylan backbone quantity, indicating that backbone synthesis and substitution can be uncoupled. Although the stems are weakened, the xylem vessels are not collapsed, and the plants grow to normal size. The xylan in these plants shows improved extractability from the cell wall, is composed of a single monosaccharide, and requires fewer enzymes for complete hydrolysis. These findings have implications for our understanding of the synthesis and function of xylan in plants. The results also demonstrate the potential for manipulating and simplifying the structure of xylan to improve the properties of lignocellulose for bioenergy and other uses.