Combining data sets of satellite-retrieved products for basin-scale water balance study: 2. Evaluation on the Mississippi Basin and closure correction model

In this study, we applied the integration methodology developed in the companion paper by Aires (2014) by using real satellite observations over the Mississippi Basin. The methodology provides basin-scale estimates of the four water budget components (precipitation P, evapotranspiration E, water storage change Delta S, and runoff R) in a two-step process: the Simple Weighting (SW) integration and a Postprocessing Filtering (PF) that imposes the water budget closure. A comparison with in situ observations of P and E demonstrated that PF improved the estimation of both components. A Closure Correction Model (CCM) has been derived from the integrated product (SW+PF) that allows to correct each observation data set independently, unlike the SW+PF method which requires simultaneous estimates of the four components. The CCM allows to standardize the various data sets for each component and highly decrease the budget residual (P - E - Delta S - R). As a direct application, the CCM was combined with the water budget equation to reconstruct missing values in any component. Results of a Monte Carlo experiment with synthetic gaps demonstrated the good performances of the method, except for the runoff data that has a variability of the same order of magnitude as the budget residual. Similarly, we proposed a reconstruction of Delta S between 1990 and 2002 where no Gravity Recovery and Climate Experiment data are available. Unlike most of the studies dealing with the water budget closure at the basin scale, only satellite observations and in situ runoff measurements are used. Consequently, the integrated data sets are model independent and can be used for model calibration or validation.

Solution processable diketopyrrolopyrrole (DPP) cored small molecules with BODIPY end groups as novel donors for organic solar cells

Two novel triads based on a diketopyrrolopyrrole (DPP) central core and two 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) units attached by thiophene rings have been synthesised having high molar extinction coefficients. These triads were characterised and used as donor materials in small molecule, solution processable organic solar cells. Both triads were blended with PC71BM as an acceptor in different ratios by wt% and their photovoltaic properties were studied. For both the triads a modest photovoltaic performance was observed, having an efficiency of 0.65%. Moreover, in order to understand the ground and excited state properties and vertical absorption profile of DPP and BODIPY units within the triads, theoretical DFT and TDDFT calculations were performed.

Enhanced non-homologous end joining contributes toward synthetic lethality of pathological RAD51C mutants with poly (ADP-ribose) polymerase

Here, we show that PARP inhibitor-mediated cell death of RAD51C-deficient cells occur by NHEJ-driven illegitimate repair of one-ended double-strand breaks, and the hypomorphic RAD51C pathological mutant cells can be targeted by `synergistic toxicity' induced by low-dose PARP inhibitor and IR.Poly (ADP-ribose) polymerase 1 (PARP1) inhibitors are actively under clinical trials for the treatment of breast and ovarian cancers that arise due to mutations in BRCA1 and BRCA2. The RAD51 paralog RAD51C has been identified as a breast and ovarian cancer susceptibility gene. The pathological RAD51C mutants that were identified in cancer patients are hypomorphic with partial repair function. However, targeting cancer cells that express hypomorphic mutants of RAD51C is highly challenging. Here, we report that RAD51C-deficient cells can be targeted by a `synthetic lethal' approach using PARP inhibitor and this sensitivity was attributed to accumulation of cells in the G(2)/M and chromosomal aberrations. In addition, spontaneous hyperactivation of PARP1 was evident in RAD51C-deficient cells. Interestingly, RAD51C-negative cells exhibited enhanced recruitment of non-homologous end joining (NHEJ) proteins onto chromatin and this accumulation correlated with increased activity of error-prone NHEJ as well as genome instability leading to cell death. Notably, inhibition of DNA-PKcs or depletion of KU70 or Ligase IV rescued this phenotype. Strikingly, stimulation of NHEJ by low dose of ionizing radiation (IR) in the PARP inhibitor-treated RAD51C-deficient cells and cells expressing pathological RAD51C mutants induced enhanced toxicity `synergistically'. These results demonstrate that cancer cells arising due to hypomorphic mutations in RAD51C can be specifically targeted by a `synergistic approach' and imply that this strategy can be potentially applied to cancers with hypomorphic mutations in other homologous recombination pathway genes.

Low-Order Harmonic Suppression for Open-End Winding IM With Dodecagonal Space Vector Using a Single DC-Link Supply

This paper proposes a technique to suppress low-order harmonics for an open-end winding induction motor drive for a full modulation range. One side of the machine is connected to a main inverter with a dc power supply, whereas the other inverter is connected to a capacitor from the other side. Harmonic suppression (with complete elimination of fifth- and seventh-order harmonics) is achieved by realizing dodecagonal space vectors using a combined pulsewidth modulation (PWM) control for the two inverters. The floating capacitor voltage is inherently controlled during the PWM operation. The proposed PWM technique is shown to be valid for the entire modulation range, including overmodulation and six-step mode of operation of the main inverter. Experimental results have been presented to validate the proposed technique.

ANRC Hybrid Test Bed Implementation and an End-to-End Performance Characterization of Dynamic Spectrum Access

An abundance of spectrum access and sensing algorithms are available in the dynamic spectrum access (DSA) and cognitive radio (CR) literature. Often, however, the functionality and performance of such algorithms are validated against theoretical calculations using only simulations. Both the theoretical calculations and simulations come with their attendant sets of assumptions. For instance, designers of dynamic spectrum access algorithms often take spectrum sensing and rendezvous mechanisms between transmitter-receiver pairs for granted. Test bed designers, on the other hand, either customize so much of their design that it becomes difficult to replicate using commercial off the shelf (COTS) components or restrict themselves to simulation, emulation /hardware-in-Ioop (HIL), or pure hardware but not all three. Implementation studies on test beds sophisticated enough to combine the three aforementioned aspects, but at the same time can also be put together using COTS hardware and software packages are rare. In this paper we describe i) the implementation of a hybrid test bed using a previously proposed hardware agnostic system architecture ii) the implementation of DSA on this test bed, and iii) the realistic hardware and software-constrained performance of DSA. Snapshot energy detector (ED) and Cumulative Summation (CUSUM), a sequential change detection algorithm, are available for spectrum sensing and a two-way handshake mechanism in a dedicated control channel facilitates transmitter-receiver rendezvous.

Evaluation of Precipitation Retrievals From Orbital Data Products of TRMM Over a Subtropical Basin in India

The spatial error structure of daily precipitation derived from the latest version 7 (v7) tropical rainfall measuring mission (TRMM) level 2 data products are studied through comparison with the Asian precipitation highly resolved observational data integration toward evaluation of the water resources (APHRODITE) data over a subtropical region of the Indian subcontinent for the seasonal rainfall over 6 years from June 2002 to September 2007. The data products examined include v7 data from the TRMM radiometer Microwave Imager (TMI) and radar precipitation radar (PR), namely, 2A12, 2A25, and 2B31 (combined data from PR and TMI). The spatial distribution of uncertainty from these data products were quantified based on performance metrics derived from the contingency table. For the seasonal daily precipitation over a subtropical basin in India, the data product of 2A12 showed greater skill in detecting and quantifying the volume of rainfall when compared with the 2A25 and 2B31 data products. Error characterization using various error models revealed that random errors from multiplicative error models were homoscedastic and that they better represented rainfall estimates from 2A12 algorithm. Error decomposition techniques performed to disentangle systematic and random errors verify that the multiplicative error model representing rainfall from 2A12 algorithm successfully estimated a greater percentage of systematic error than 2A25 or 2B31 algorithms. Results verify that although the radiometer derived 2A12 rainfall data is known to suffer from many sources of uncertainties, spatial analysis over the case study region of India testifies that the 2A12 rainfall estimates are in a very good agreement with the reference estimates for the data period considered.

An Open-End winding IM drive with Multilevel 12-sided Polygonal Vectors with Symmetric Triangles

Multilevel inverters with hexagonal voltage space vector structures have improved performance of induction motor drives compared to that of the two level inverters. Further reduction in the torque ripple on the motor shaft is possible by using multilevel dodecagonal (12-sided polygon) voltage space vector structures. The advantages of dodecagonal voltage space vector based PWM techniques are the complete elimination of fifth and seventh harmonics in phase voltages for the full modulation range and the extension of linear modulation range. This paper proposes an inverter circuit topology capable of generating multilevel dodecagonal voltage space vectors with symmetric triangles, by cascading two asymmetric three level inverters with isolated H-Bridges. This is made possible by proper selection of DC link voltages and the selection of resultant switching states for the inverters. In this paper, a simple PWM timing calculation method is proposed. Experimental results have also been presented in this paper to validate the proposed concept.

Inhibition of nonhomologous end joining to increase the specificity of CRISPR/Cas9 genome editing

DNA repair, one of the fundamental processes occurring in a cell, safeguards the genome and maintains its integrity. Among various DNA lesions, double-strand breaks are considered to be the most deleterious, as they can lead to potential loss of genetic information, if not repaired. Non-homologous end joining (NHEJ) and homologous recombination are two major double-strand break repair pathways. SCR7, a DNA ligase IV inhibitor, was recently identified and characterized as a potential anticancer compound. Interestingly, SCR7 was shown to have several applications, owing to its unique property as an NHEJ inhibitor. Here, we focus on three main areas of research in which SCR7 is actively being used, and discuss one of the applications, i.e. genome editing via CRISPR/Cas, in detail. In the past year, different studies have shown that SCR7 significantly increases the efficiency of precise genome editing by inhibiting NHEJ, and favouring the error-free homologous recombination pathway, both in vitro and in vivo. Overall, we discuss the current applications of SCR7 to shed light on the unique property of the small molecule of having distinct applications in normal and cancer cells, when used at different cellular concentrations.

Microhomology-mediated end joining is the principal mediator of double-strand break repair during mitochondrial DNA lesions

Mitochondrial DNA (mtDNA) deletions are associated with various mitochondrial disorders. The deletions identified in humans are flanked by short, directly repeated mitochondrial DNA sequences; however, the mechanism of such DNA rearrangements has yet to be elucidated. In contrast to nuclear DNA (nDNA), mtDNA is more exposed to oxidative damage, which may result in double-strand breaks (DSBs). Although DSB repair in nDNA is well studied, repair mechanisms in mitochondria are not characterized. In the present study, we investigate the mechanisms of DSB repair in mitochondria using in vitro and ex vivo assays. Whereas classical NHEJ (C-NHEJ) is undetectable, microhomology-mediated alternative NHEJ efficiently repairs DSBs in mitochondria. Of interest, robust microhomology-mediated end joining (MMEJ) was observed with DNA substrates bearing 5-, 8-, 10-, 13-, 16-, 19-, and 22-nt microhomology. Furthermore, MMEJ efficiency was enhanced with an increase in the length of homology. Western blotting, immunoprecipitation, and protein inhibition assays suggest the involvement of CtIP, FEN1, MRE11, and PARP1 in mitochondrial MMEJ. Knock-down studies, in conjunction with other experiments, demonstrated that DNA ligase III, but not ligase IV or ligase I, is primarily responsible for the final sealing of DSBs during mitochondrial MMEJ. These observations highlight the central role of MMEJ in maintenance of mammalian mitochondrial genome integrity and is likely relevant for deletions observed in many human mitochondrial disorders.

Determinantal point processes in the plane from products of random matrices

We show that the density of eigenvalues for three classes of random matrix ensembles is determinantal. First we derive the density of eigenvalues of product of k independent n x n matrices with i.i.d. complex Gaussian entries with a few of matrices being inverted. In second example we calculate the same for (compatible) product of rectangular matrices with i.i.d. Gaussian entries and in last example we calculate for product of independent truncated unitary random matrices. We derive exact expressions for limiting expected empirical spectral distributions of above mentioned ensembles.

Nanomechanical Mapping, Hierarchical Polymer Dynamics, and Miscibility in the Presence of Chain-End Grafted Nanoparticles

To improve the spatial distribution of nano particles in a polymeric host and to enhance the interfacial interaction with the host, the use of chain-end grafted nanoparticle has gained popularity in the field of polymeric nanocomposites. Besides changing the material properties of the host, these grafted nanoparticles strongly alter the dynamics of the polymer chain at both local and cooperative length scales (relaxations) by manipulating the enthalpic and entropic interactions. It is difficult to map the distribution of these chain-end grafted nanoparticles in the blend by conventional techniques, and herein, we attempted to characterize it by unique technique(s) like peak force quantitative nanomechanical mapping (PFQNM) through AFM (atomic force microscopy) imaging and dielectric relaxation spectroscopy (DRS). Such techniques, besides shedding light on the spatial distribution of the nanoparticles, also give critical information on the changing elasticity at smaller length scales and hierarchical polymer chain dynamics in the vicinity of the nanoparticles. The effect of one-dimensional rodlike multiwall carbon nanotubes (MWNTs), with the characteristic dimension of the order of the radius of gyration of the polymeric chain, on the phase miscibility and chain dynamics in a classical LCST mixture of polystyrene/ poly(vinyl methyl ether) (PS/PVME) was examined in detail using the above techniques. In order to tune the localization of the nanotubes, different molecular weights of PS (13, 31, and 46 kDa), synthesized using RAFT (reversible addition fragmentation chain transfer) polymerization, was grafted onto MWNTs in situ. The thermodynamic miscibility in the blends was assessed by low-amplitude isochronal temperature sweeps, the spatial distribution of MWNTs in the blends was evaluated by PFQNM, and the hierarchical polymer chain dynamics was studied by DRS. It was observed that the miscibility, concentration fluctuation, and cooperative relaxations of the PS/PVME blends are strongly governed by the spatial distribution of MWNTs in the blends. These findings should help guide theories and simulations of hierarchical chain dynamics in LCST mixtures containing rodlike nanoparticles.

A glucose-centric perspective of hyperglycemia

Digestion of food in the intestines converts the compacted storage carbohydrates, starch and glycogen, to glucose. After each meal, a flux of glucose (>200 g) passes through the blood pool (4-6 g) in a short period of 2 h, keeping its concentration ideally in the range of 80-120 mg/100 mL. Tissue-specific glucose transporters (GLUTs) aid in the distribution of glucose to all tissues. The balance glucose after meeting the immediate energy needs is converted into glycogen and stored in liver (up to 100 g) and skeletal muscle (up to 300 g) for later use. High blood glucose gives the signal for increased release of insulin from pancreas. Insulin binds to insulin receptor on the plasma membrane and activates its autophosphorylation. This initiates the post-insulin-receptor signal cascade that accelerates synthesis of glycogen and triglyceride. Parallel control by phos-dephos and redox regulation of proteins exists for some of these steps. A major action of insulin is to inhibit gluconeogensis in the liver decreasing glucose output into blood. Cases with failed control of blood glucose have alarmingly increased since 1960 coinciding with changed life-styles and large scale food processing. Many of these turned out to be resistant to insulin, usually accompanied by dysfunctional glycogen storage. Glucose has an extended stay in blood at 8 mM and above and then indiscriminately adds on to surface protein-amino groups. Fructose in common sugar is 10-fold more active. This random glycation process interferes with the functions of many proteins (e.g., hemoglobin, eye lens proteins) and causes progressive damage to heart, kidneys, eyes and nerves. Some compounds are known to act as insulin mimics. Vanadium-peroxide complexes act at post-receptor level but are toxic. The fungus-derived 2,5-dihydroxybenzoquinone derivative is the first one known to act on the insulin receptor. The safe herbal products in use for centuries for glucose control have multiple active principles and targets. Some are effective in slowing formation of glucose in intestines by inhibiting alpha-glucosidases (e.g., salacia/saptarangi). Knowledge gained from French lilac on active guanidine group helped developing Metformin (1,1-dimethylbiguanide) one of the popular drugs in use. One strategy of keeping sugar content in diets in check is to use artificial sweeteners with no calories, no glucose or fructose and no effect on blood glucose (e.g., steviol, erythrytol). However, the three commonly used non-caloric artificial sweetener's, saccharin, sucralose and aspartame later developed glucose intolerance, the very condition they are expected to evade. Ideal way of keeping blood glucose under 6 mM and HbAlc, the glycation marker of hemoglobin, under 7% in blood is to correct the defects in signals that allow glucose flow into glycogen, still a difficult task with drugs and diets.

Nanomechanical Mapping, Hierarchical Polymer Dynamics, and Miscibility in the Presence of Chain-End Grafted Nanoparticles

To improve the spatial distribution of nano particles in a polymeric host and to enhance the interfacial interaction with the host, the use of chain-end grafted nanoparticle has gained popularity in the field of polymeric nanocomposites. Besides changing the material properties of the host, these grafted nanoparticles strongly alter the dynamics of the polymer chain at both local and cooperative length scales (relaxations) by manipulating the enthalpic and entropic interactions. It is difficult to map the distribution of these chain-end grafted nanoparticles in the blend by conventional techniques, and herein, we attempted to characterize it by unique technique(s) like peak force quantitative nanomechanical mapping (PFQNM) through AFM (atomic force microscopy) imaging and dielectric relaxation spectroscopy (DRS). Such techniques, besides shedding light on the spatial distribution of the nanoparticles, also give critical information on the changing elasticity at smaller length scales and hierarchical polymer chain dynamics in the vicinity of the nanoparticles. The effect of one-dimensional rodlike multiwall carbon nanotubes (MWNTs), with the characteristic dimension of the order of the radius of gyration of the polymeric chain, on the phase miscibility and chain dynamics in a classical LCST mixture of polystyrene/ poly(vinyl methyl ether) (PS/PVME) was examined in detail using the above techniques. In order to tune the localization of the nanotubes, different molecular weights of PS (13, 31, and 46 kDa), synthesized using RAFT (reversible addition fragmentation chain transfer) polymerization, was grafted onto MWNTs in situ. The thermodynamic miscibility in the blends was assessed by low-amplitude isochronal temperature sweeps, the spatial distribution of MWNTs in the blends was evaluated by PFQNM, and the hierarchical polymer chain dynamics was studied by DRS. It was observed that the miscibility, concentration fluctuation, and cooperative relaxations of the PS/PVME blends are strongly governed by the spatial distribution of MWNTs in the blends. These findings should help guide theories and simulations of hierarchical chain dynamics in LCST mixtures containing rodlike nanoparticles.