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Keeping in mind the immense biological potential of chalcones and sulfonamide scaffolds, a library of sulfonamide chalcones has been synthesized and evaluated for in vitro antifilarial assay against human lymphatic filarial parasite Brugia malayi. Experimental evidence showcased for the first time the potential of some sulfonamide chalcones as effective and safe antifilarial lead molecules against human lymphatic filarial parasite B. malayi. Sulfonamide chalcones 4d, 4p, 4q, 4t and 4aa displayed the significantly wide therapeutic window. Particularly chalcones with halogen substitution in aromatic ring proved to be potent antifilarial agents against Brugia malayi. Sulphonamide chalcones with lipophilic methyl moiety (4q and 4aa) at para position of terminal phenyl rings of compounds were found to have remarkable antifilarial activities with therapeutic efficacy. Observed preliminary evidence of apoptosis by effective chalcone derivatives envisaged its fair possibility to inhibit folate pathway with consequent defect in DNA synthesis.

Rapid growth in e-commerce has altered the ability of jurisdictions to enforce commodity taxes on a destination basis. This results in different effective tax rates depending on the way in which goods and services are purchased and the characteristics of both the products and the sellers. We discuss the arguments for the destination principle as the appropriate place-of-taxation rule for consumption taxation of cross-border trade. We analyze various recent reforms to the value-added tax in the European Union in response to e-commerce. We then examine various policy options in the USA—maintaining the status quo, changing nexus rules, states adopting information reporting, and national reforms that require firms to remit taxes regardless of physical presence—and relate them to the recent European reforms. We conclude based on our analysis and the recent European Union experience that reforms at the national level appear to be the important next step to enforcing commodity taxes at destination in the USA.

Forty-five weaner Chinchilla rabbits (42-d-old, average weight 619 g) randomly assigned to three equal treatments, control with no probiotic and the other two with probiotics (107 CFU/g concentrate) Lactobacillus acidophilus and Lactococcus lactis. They were reared in individual cages and fed on ad libitum concentrate and wilted Lucerne (Medicago sativa) up to 91 d of age. Compared to control L. acidophilus improved weight gain (24.5 vs. 22.5 g/d, P < .05), whereas it was intermediate with L. lactis. Both probiotics improved the feed conversion ratio (3.91 and 3.96 vs. 4.34, P < .05) but no effect on dry matter intake (95.8 and 92.7 vs. 98.0 g). Dry matter and organic matter digestibility improved with L. acidophilus (72.8 vs. 67.0%, P < .05), whereas it was intermediate with L. lactis. Probiotics also improved (P < .05) digestibility of crude protein (82.7 vs. 74.9%) and neutral detergent fibre (41.9 vs. 29.4%). Nitrogen utilization improved with reduced faecal excretion in probiotics-supplemente...

Similarity search finds the most similar matches in an object collection for a given query; making it an important problem across a wide range of disciplines such as web search, image recognition and protein sequencing. Practical implementations of High Dimensional Similarity Search (HDSS) search across billions of possible solutions for multiple queries in real time, making its performance and efficiency a significant challenge. Existing clusters and datacenters use commercial multicore hardware to perform search, which may not provide the optimal performance and performance per Watt. This work explores the performance, power and cost benefits of using throughput accelerators like GPUs to perform similarity search for query cohorts even under tight deadlines. We propose optimized implementations of similarity search for both the host and the accelerator. Augmenting existing Xeon servers with accelerators results in a 3× improvement in throughput per machine, resulting in a more than 2.5× reduction in cost of ownership, even for discounted Xeon servers. Replacing a Xeon based cluster with an accelerator based cluster for similarity search reduces the total cost of ownership by more than 6× to 16× while consuming significantly less power than an ARM based cluster.

An environmentally benign novel strategy is developed for the synthesis of tetrahydrobenzo[b]pyrans by using thiamine mononitrate as a green catalyst, with the help of a conventional as well as non-conventional energy source. Synthesis of tetrahydrobenzo[b]pyrans is achieved by one pot condensation of aromatic aldehydes, malononitrile and dimedone in a water–ethanol system. Use of aqueous reaction media, mild conditions, water stable catalyst and energy plummeting process as well as excellent yield, are the key features in completing the reaction. This method excludes the use of volatile organic solvents, tedious workup and column chromatographic purification of compounds, making the method greener, convenient and superior.

Local sales tax rates influence the location of retail activity. This paper develops a theory and empirical identification strategy for studying sales tax competition with “multiple federations,” as exemplified by multiple counties each containing several cities. In addition to strategic interactions with nearby cities and a city’s own county, city tax rates are influenced by the tax rates of neighboring counties. Cities react heterogeneously to own-county sales tax rates depending on distance to the county border. Using data on the driving time to county borders and a comprehensive cross-section of local sales tax rates, I exploit variation in proximity to county borders to identify vertical fiscal competition. Cities located near county borders react more intensely to their county’s tax rate in comparison to towns at the interior. An increase in the neighboring county tax rate raises city tax rates in nearby counties.

Technological innovations facilitating e-commerce have had major effects on consumer behavior and firm organization in the retail sector, but the effects of these new transaction technologies on fiscal systems remain unknown. We extend models of commodity tax competition to include multiple types of commodities, trade, and remote commerce, assuming, in accordance with current policy, that e-commerce is taxed at destination while cross-border shopping is taxed at origin. When the cost of online shopping falls, we show that equilibrium tax rates and revenues decrease in large, core jurisdictions but increase in small, peripheral ones, reducing tax differentials. Policy commentators warn that e-commerce erodes tax revenue – true enough for some governments – but, more accurately, changing transaction costs can generate entirely new commercial and fiscal equilibria that ultimately “redistribute” tax revenues from jurisdictions with concentrations of traditional vendors toward others. With some reinterpretation, the model is also adapted to analyze profit-tax competition when firms can respond to high taxes both through profit-shifting and through relocation, each dependent on transactions costs. Changes in technology may again redistribute tax revenues from high-tax to low-tax jurisdictions.

Present study was conducted to develop a novel Bimatoprost (BIM) nanoparticles loaded pH-sensitive in-situ gel for the treatment of glaucoma. BIM loaded solid lipid nanoparticles were prepared by high shear homogenization followed by probe sonication method. Glyceryl Monostearate (GMS) was used as solid lipid and Tween 80 as surfactant. Optimization of nanoformulation was done by 32 full factorial design using Design Expert Software 11.0.5. GMS and Tween 80 concentrations were the independent variables and particle size, PDI, zeta potential (ZP) and % entrapment efficiency (EE) were dependent variables. The optimized BIM loaded nanoparticles batch (BIM-SLN4) was further incorporated into carbopol 941 to form nanoparticles loaded in situ gel (SLN-ISG). A total of 5 batches (SLN-ISG1-SLN-ISG5) were prepared by varying the concentration of carbopol 941 from 0.05%w/v to 0.25%w/v. SLN-ISG3 was selected as optimized batch based on its gelling capacity and viscosity. In-vitro and ex-vivo studies of BIM-SLN4, SLN-ISG3 showed drug release for a prolonged period of time. HET-CAM test revealed that the formulation is non-irritant and thus can be well tolerated when instilled in the eye. Histopathological studies also revealed no signs of tissue damage. Thus, SLN-ISG can offer improved management of glaucoma.

In the field of biomedical application, the polymer composite has been played a very challenging role and its used has been increasing since it possess good tribological properties when reinforce with appropriate material. In this regard, PLA (poly lactic acid) and it’s composite with HAP (Hydroxyapatite) was studied for its tribological behaviour which may be used as an implant material. PLA with varying percentage of HAP nanoparticles was examined on linear reciprocating tribometer under dry sliding test for specific wear rate. Design of experiment was based on Taguchi technique for optimizing specific wear rate parameter. In this study, effect of reinforcement and operating parameters that is load and frequency on tribological performance of PLA Nano composite was studied. ANOVA (Analysis of Variance) has been used to determine the influence of each parameter on wear characteristics. Regression analysis was used to establish a regression equation between all affecting parameters. The results shows that reinforcement plays a major role while load and frequency plays an average role on wear characteristic of PLA Nano composite. It was observed that PLA reinforced with HAP nanoparticle significantly improve wear characteristic up to 5% of reinforcement while beyond it, there is reverse nature of composite. The optimum parameter for wear rate were 5% reinforcement of HAP, 80 N of load, and 7 Hz frequency.

Curative therapies for radioiodine-refractory differentiated thyroid cancer remain lacking. However, oral multikinase inhibitors often allow for disease control and improved progression-free survival. Two agents, lenvatinib and sorafenib, have been approved for radioiodine-refractory differentiated thyroid cancer on the basis of phase III clinical trials showing marked response rates and improved progression-free survival over placebo. Several other multikinase inhibitors, including apatinib, axitinib, cabozantinib, pazopanib, sunitinib and vandetanib, have also been studied in phase II clinical trials, with varying response rates and comparable progression-free survival. Selective kinase inhibitors, including dabrafenib, vemurafenib, selumetinib and gefitinib, offer a more targeted approach and have also been studied in phase II clinical trials. While the emergence of these treatments has changed the landscape of management of advanced thyroid cancer, clinical challenges remain, and there are many areas of ongoing research.

The additive manufacturing of energetic materials has received worldwide attention. Here, an ink formulation is developed with only 10 wt% of polymers, which can bind a 90 wt% nanothermite using a simple direct-writing approach. The key additive in the ink is a hybrid polymer of poly(vinylidene fluoride) (PVDF) and hydroxy propyl methyl cellulose (HPMC) in which the former serves as an energetic initiator and a binder, and the latter is a thickening agent and the other binder, which can form a gel. The rheological shear-thinning properties of the ink are critical to making the formulation at such high loadings printable. The Young's modulus of the printed stick is found to compare favorably with that of poly(tetrafluoroethylene) (PTFE), with a particle packing density at the theoretical maximum. The linear burn rate, mass burn rate, flame temperature, and heat flux are found to be easily adjusted by varying the fuel/oxidizer ratio. The average flame temperatures are as high as ≈2800 K with near-complete combustion being evident upon examination of the postcombustion products.

Introduction: In the present study, fruit extracts of Momordica cochinchinensis (Cucurbitaceae) and Momordica balsamina (Cucurbitaceae) were investigated for analgesic activity by Eddy’s hot plate and Tail immersion method. Materials and Methods: The extracts were prepared successively using powdered material with petroleum ether, ethanol, and water, and concentrated under vacuum and were evaluated for analgesic activity at three dose level (100, 200, and 400 mg/kg). Results and Discussion: In Eddy’s hot plate method, oral administration of petroleum ether extracts of both the plants at the dose of 200 mg/kg (P < 0.01) and 400 mg/kg (P < 0.001) significantly reduced the thermal stimulation. Analgesic activity of petroleum ether extracts of both plants at the dose of 400 mg/kg after 90 min was comparable to standard drug pentazocine (10 mg/kg). In tail immersion method, petroleum ether extract at the dose of 100 mg/kg (P < 0.05), 200 mg/kg, and 400 mg/kg (P < 0.01) and alcoholic extract at the dose of 200 mg/kg and 400 mg/kg (P < 0.05) of both plant material has shown significant analgesic activity and was comparable to standard drug pentazocine (10 mg/kg) after 90 min. Conclusion: It is concluded that petroleum ether extracts of both plant material have central analgesic effects.

Pyrrolidone-carboxylate peptidase (PCP) catalyzes the removal of an unusual amino acid, L-pyroglutamate (pG), from the N-termini of peptides and proteins. It has implications in the functional regulation of different peptides in both prokaryotes and eukaryotes. However, the pG-recognition mechanism of the PCP enzyme remains largely unknown. Here, crystal structures of PCP I from Deinococcus radiodurans (PCPdr) are reported in pG-free and pG-bound forms at resolutions of 1.73 and 1.55 Å, respectively. Four protomers in PCPdr form a tetrameric structure. The residues responsible for recognizing the pG residue are mostly contributed by a flexible loop (loop A) that is present near the active site. These residues are conserved in all known PCPs I, including those from mammals. Phe9 and Phe12 of loop A form stacking interactions with the pyrrolidone ring of pG, while Asn18 forms a hydrogen bond to OE of pG. The main chain of a nonconserved residue, Leu71, forms two hydrogen bonds to NH and OE of pG. Thus, pG is recognized in the S1 substrate subsite of the enzyme by both van der Waals and polar interactions, which provide specificity for the pG residue of the peptide. In contrast to previously reported PCP I structures, the PCPdr tetramer is in a closed conformation with an inaccessible active site. The structures show that the active site can be accessed by the substrates via disordering of loop A. This disordering could also prevent product inhibition by releasing the bound pG product from the S1 subsite, thus allowing the enzyme to engage a fresh substrate.

A single-step intramolecular radical cascade reaction of diynes and thioacetic acid in the presence of a catalytic amount of azobis(isobutyronitrile) as a radical initiator has been developed to synthesize thiophenes. This method allows easy and effective construction of a thiophene scaffold having 3,4-fused-ring substitution and unsubstituted 2,5-positions for further functionalization and polymerization. Using this method, derivatives of cyclopenta[ c]thiophene, 3,4-ethylenedioxythiophene, and thiophene-containing spirocyclic compound have been synthesized.

OBJECTIVES: To examine the outcomes of e-learning or blended learning interventions in undergraduate dental radiology curricula and analyze the nature of the knowledge levels addressed in learning interventions. METHODS: A systematic literature review was performed using a search strategy based on MeSH key words specific to the focus question and indexed in the MEDLINE database. The search again was supplemented by hand-searching of selected journals. Data were extracted relating to outcomes of knowledge and student perceptions. Analysis of the e-learning intervention was performed using a new framework to examine the level of knowledge undertaken: (1) remember/understand (2) analysis or evaluation or diagnosis and (3) performance (“knows how” or “shows how”). RESULTS: From the selected 17 papers, 11 were positive about student reported outcomes of the interventions, and 8 reported evidence that e-learning interventions enhanced learning. Out of the included studies, 8 used e-learning at the level of remember/understand, 4 at the level of analysis/evaluate/diagnosis, and 5 at the level of performance (“knows how,” “shows how”). CONCLUSIONS: The learning objectives, e-learning intervention, outcome measures and reporting methods were diverse and not well reported. This makes comparison between studies and an understanding of how interventions contributed to learning impractical. Future studies need to define “knowledge” levels and performance tasks undertaken in the planning and execution of e-learning interventions and their assessment methods. Such a framework and approach will focus our understanding in what ways e-learning is effective and how it contributes to better evidence-based e-learning experiences.

Today, an ever increasing amount of transistors are packed into processor designs with extra features to support a broad range of applications. As a consequence, processors are becoming more and more complex and power hungry. At the same time, they only sustain an average performance for a wide variety of applications while not providing the best performance for specific applications. In this paper, we demonstrate through a carefully designed modern data processing system called RAPID and a simple, low-power processor specially tailored for data processing that at least an order of magnitude performance/power improvement in SQL processing can be achieved over a modern system running on today's complex processors. RAPID is designed from the ground up with hardware/software co-design in mind to provide architecture-conscious extreme performance while consuming less power in comparison to the modern database systems. The paper presents in detail the design and implementation of RAPID, a relational, columnar, in-memory query processing engine supporting analytical query workloads.

Objective— Tissue macrophages induce and perpetuate proinflammatory responses, thereby promoting metabolic and cardiovascular disease. Lipoprotein lipase (LpL), the rate-limiting enzyme in blood triglyceride catabolism, is expressed by macrophages in atherosclerotic plaques. We questioned whether LpL, which is also expressed in the bone marrow (BM), affects circulating white blood cells and BM proliferation and modulates macrophage retention within the artery. Approach and Results— We characterized blood and tissue leukocytes and inflammatory molecules in transgenic LpL knockout mice rescued from lethal hypertriglyceridemia within 18 hours of life by muscle-specific LpL expression (MCKL0 mice). LpL-deficient mice had ≈40% reduction in blood white blood cell, neutrophils, and total and inflammatory monocytes (Ly6C/G hi ). LpL deficiency also significantly decreased expression of BM macrophage-associated markers (F4/80 and TNF-α [tumor necrosis factor α]), master transcription factors (PU.1 and C/EBPα), and colony-stimulating factors (CSFs) and their receptors, which are required for monocyte and monocyte precursor proliferation and differentiation. As a result, differentiation of macrophages from BM-derived monocyte progenitors and monocytes was decreased in MCKL0 mice. Furthermore, although LpL deficiency was associated with reduced BM uptake and accumulation of triglyceride-rich particles and macrophage CSF–macrophage CSF receptor binding, triglyceride lipolysis products (eg, linoleic acid) stimulated expression of macrophage CSF and macrophage CSF receptor in BM-derived macrophage precursor cells. Arterial macrophage numbers decreased after heparin-mediated LpL cell dissociation and by genetic knockout of arterial LpL. Reconstitution of LpL-expressing BM replenished aortic macrophage density. Conclusions— LpL regulates peripheral leukocyte levels and affects BM monocyte progenitor differentiation and aortic macrophage accumulation.

The standard partial equilibrium formula for pass-through substantially mismeasures incidence in the presence of demand or supply interdependencies. We study general equilibrium tax incidence in a perfectly competitive, multiproduct setting. If only one product is taxed, the general equilibrium incidence will always be greater on the consumer than suggested by the standard incidence formula. If the tax changes on multiple related commodities, while maintaining perfect competition, a necessary condition for overshifting is that the related commodities are substitutes. Pass-through greater than one-hundred percent is not sufficient to infer market structure. When empirically estimating pass-through, pass-through estimates capture the direct effect of the tax on the market, the indirect feedback effects resulting from price and tax changes in other markets and taxation of inputs to production. Empirically applying our theory to estimate pass-through in alcohol markets, we show that demand interdependencies and simultaneous tax changes on related products are important.

We develop a tax competition model that allows for the setting of both an origin-based and a destination-based commodity tax rate in the presence of avoidance and evasion. In the presence of evasion, jurisdictions will give cross-border shoppers tax preferential treatment, thus not fully exploiting the potential of destination-based taxation. Moreover, the divergence between origin-based and destination-based taxes is stronger when the incentives for consumers' tax-arbitrage opportunities increase. The United States is one example of many such systems. While sales taxes are due at the point of sale, use taxes are due on goods purchased out-of-state. We document that when able to set both rates, a majority of jurisdictions levy destination-based use taxes at a lower rate than origin-based sales taxes. In response to changes in state-level policies that increase tax avoidance opportunities, the results of the empirical model broadly confirm our theory.

Case: It is rare to find a case report on combined recurvatum and valgus deformity of the knee with associated patellar instability due to a depressed lateral tibial plateau in a young adult with multiple epiphyseal dysplasia. We treated such a patient with single-stage osseous and soft-tissue procedures and achieved a stable, well-aligned, pain-free, and mobile joint. Conclusion: Patellar instability with genu recurvatum and genu valgum leading to reduced range of motion of the knee in multiple epiphyseal dysplasia shows mechanical and functional improvement following single-stage surgical intervention, thereby improving quality of life.

Competition at the subnational level concerns how jurisdictions set tax, spending, or regulatory policies while accounting for the fact that these policies affect the locations of individuals, firm...

Summary Thirty-six Malpura lambs (28 day old and 6.7 ± 0.25 kg BW) were distributed equally in three groups having six males and six female. They were ad libitum fed individually three different experimental diets containing calcium soap of fatty acids (CA-FA) at 0 (T1) and 40 (T2 and T3) g/kg concentrate up to six months of age. Animals in T3 were supplemented additionally with 40 mg DL-α-tocopherol acetate/kg of concentrate. The roughage moiety included ad libitum dry Prosopis cineraria and fresh Azadirachata indica leaves. All the lambs were allowed to suckle from their dam up to weaning (90 day of age). Supplementation of Ca-FA improved weight gain and feed conversion ratio during both pre- (28–90 days) and post-weaning (91–180 days) phases; however, no effect of DL-α-tocopherol was observed. Metabolic parameters during post-weaning phase revealed non-significant effect on digestibility but improved nitrogen balance in the test groups. The effect on biochemical attributes did not show any significant alteration in ruminal parameters, blood biochemicals and urinary purine derivatives. Carcass traits revealed higher (p

Laparoscopic kidney transplantation (LKT) is well accepted modality of treatment for ESRD patients at our center. Usually, the kidney is inserted through small Pfannenstiel incision. With the permission of the Internal Review Board, we carried out LKT in eight female recipients following insertion of the kidney through the vagina. The kidney was procured by the retroperitoneoscopic approach. Antibiotic prophylaxis was given. All cases were carried out successfully with immediate graft function and 100% graft and patient survival at 1 year of follow-up. Estimated glomerular filtration rate at 1 month and 1 year was similar to eight randomly selected female recipients who underwent open kidney transplantation (OKT). No analgesia was required in seven out of eight patients after the 3rd postoperative day. In summary, vaginal insertion of kidney and LKT is safe and feasible in a selected group of patients. It is associated with better analgesia and has similar allograft function as compare to OKT.

The modified nonlinear wave dynamics due to band nonparabolicity and carrier heating, arising from parametrically interacting electron–longitudinal optical phonons in a polar semiconductor is studied both theoretically and numerically. Expressions for threshold pump required for the onset of polaron-induced parametric interaction and amplification characteristics are explicitly derived. Polaronic effects along with nonparabolicity are found to be additive and result in tremendous increment in the parametric gain. At smaller magnetic field and moderate carrier concentrations, nonlinearity in energy-dependent effective electron mass and collision frequency, affects threshold and amplification characteristics strongly, which can be utilized for the construction of optical switches.

The synthesis of highly functionalized piperidines has been strategically accessed via organo-catalytic three components (in situ five components) reaction of an amine, aldehyde and 1,3-dicarbonyl compound. This imine based multi-component reaction was realized using fully green L-proline nitrate as recyclable room temperature ionic liquid. Recycling of the catalyst was possible up to five runs without loss of catalyst activity. Smaller E-factor (0.255) and process mass intensity (PMI = 3.35), high atom-economy (AE = 89.5%) and reaction mass efficiency (RME = 79.66%) demonstrates the higher environmental compatibility and sustainability of this protocol. DFT calculations showed that the L-proline catalyzed reaction proceeds by three pathways; (i) via proline enamine pathway, (ii) proline mediated aniline enamine pathway or (iii) the pathway involving iminium activation of the aldehyde to provide the Knoevenagel product.

For many years, the highest energy cost in processing has been data movement rather than computation, and energy is the limiting factor in processor design [21]. As the data needed for a single application grows to exabytes [56], there is clearly an opportunity to design a bandwidth-optimized architecture for big data computation by specializing hardware for data movement. We present the Data Processing Unit or DPU, a shared memory many-core that is specifically designed for high bandwidth analytics workloads. The DPU contains a unique Data Movement System (DMS), which provides hardware acceleration for data movement and partitioning operations at the memory controller that is sufficient to keep up with DDR bandwidth. The DPU also provides acceleration for core to core communication via a unique hardware RPC mechanism called the Atomic Transaction Engine. Comparison of a DPU chip fabricated in 40nm with a Xeon processor on a variety of data processing applications shows a 3× - 15× performance per watt advantage.CCS CONCEPTS• Computer systems organization $\rightarrow$ Multicore architectures; Special purpose systems

Computational models of drug metabolism prediction have focused mainly on cytochrome P450 enzymes, because drug–drug interactions, reactive metabolite formation, hepatotoxicity, idiosyncratic adverse drug interactions, and/or loss of efficacy of many drugs were the results of interactions with CYP450s. Metabolic regioselectivity and isoform specificity prediction models for CYP450-catalyzed reactions have reached approximately 95% accuracy. Thus, a new drug candidate is less likely to show unexpected metabolic profile due to metabolism via CYP450 pathways. For such candidates, secondary metabolic Phase I and II enzymes are likely to play an expected (or unexpected) role in drug metabolism. The importance of flavin monooxygenases (FMOs), aldehyde and alcohol dehydrogenase, monoamine oxidase from the Phase I and UDP-glucuronosyltransferase (UGT), sulfotransferase, glutathione S-transferase, and methyltransferase from Phase II has increased and United States Food and Drug Administration guidelines on NDA have specific recommendations for in vitro and in vivo testing against these enzymes. Thus, there is an urgent requirement of reliable predictive models for drug metabolism catalyzed by these enzymes. In this review, we have classified drug metabolism prediction models (site of metabolism, isoform specificity, and kinetic parameter) for these enzymes into Phase I and II. When such models are unavailable, we discuss the Quantitative Structure Activity Relationship (QSAR), pharmacophore, docking, dynamics, and reactivity studies performed for the prediction of substrates and inhibitors. Recently published models for FMO and UGT are discussed. The need for comprehensive, widely applicable, sequential primary and secondary metabolite prediction is highlighted. Potential difficulties and future prospectives in the development of such models are discussed. For further resources related to this article, please visit the WIREs website.

Contemporary frameworks for data analytics, such as Hadoop, Spark, and Flink seek to allow applications to scale performance flexibly by adding hardware nodes. However, we find that when the computation on each individual node is optimized, peripheral activities such as creating data partitions, messaging and synchronizing between nodes diminish the speedup obtainable from adding more hardware. We analyze workloads which distribute operations on correlated data—such as joins and aggregation found in SQL, text similarity searches, and image disparity computations. After optimizing computation on efficient, custom processors, we discover challenges in scaling the applications to hundreds of nodes on a high-bandwidth network. We then describe techniques to overcome these challenges towards prototyping a 512-node system which is able to execute SQL queries offloaded from a commercial database, and outperform SQL-on-hadoop and traditional parallel RDBMS executions by 173x and 7x respectively.

Wireless powering could enable the long-term operation of advanced bioelectronic devices within the human body. Although both enhanced powering depth and device miniaturization can be achieved by shaping the field pattern within the body, existing electromagnetic structures do not provide the spatial phase control required to synthesize such patterns. Here, we describe the design and operation of conformal electromagnetic structures, termed phased surfaces, that interface with non-planar body surfaces and optimally modulate the phase response to enhance the performance of wireless powering. We demonstrate that the phased surfaces can wirelessly transfer energy across anatomically heterogeneous tissues in large animal models, powering miniaturized semiconductor devices (4 cm). As an illustration of in vivo operation, we wirelessly regulated cardiac rhythm by powering miniaturized stimulators at multiple endocardial sites in a porcine animal model.

Sales taxes are due at the point of sale; use taxes are due on goods purchased abroad. We develop a tax competition model that distinguishes between tax avoidance and tax evasion. We show that the optimal use tax rate does not necessarily equal the sales tax rate. When localities set both tax rates, the divergence of the two rates is stronger when the incentives for tax avoidance opportunities increase. We assemble the first panel dataset of use tax rates. In response to changes in policies that increase tax avoidance, the results of the empirical model confirm our theory. Combining theory and empirics, we conclude that the elasticity of evasion is large or the elasticity of honesty is small.

We quantify the importance of mobility as a response to top tax rate changes in a country where migration is relatively low. A recent Spanish tax reform granted states the authority to set income tax rates for the first time. This Spanish tax reform resulted in substantial tax differences across states for high-income tax payers. To study the effect of these tax changes, we use individual-level information from Social Security records over a period of one decade. Conditional on moving, taxes have a significant effect on the location choice. A one percent increase in the net of tax rate for a region relative to others increases the probability of moving to that region by 1.5 percentage points.

We study the dynamics of policy diffusion when a first-moving jurisdiction that legalizes an activity reduces the probability of legalization in nearby later-acting jurisdictions. If a jurisdiction's firms can sell to neighboring residents, but if the good is competitively sold at every location, then policies converge: all jurisdictions legalize or all jurisdictions ban. If firms have some market power, and if the location of firms depends on the order of legalization, an early-adopting government may legalize, but an otherwise identical, but later-acting, neighboring government might not. This possible asymmetry is due to state dependence resulting from the initial distribution of firms following the first-mover's legalization. Empirically, counties that legalize the sale of fireworks first have more firework vendors just inside their border than counties that legalize later. Furthermore, counties have a longer duration to legalize fireworks if nearby counties have already adopted. State dependence resulting from a first-mover advantage contributes to the policy divergence of regulatory policies.

Technological innovations facilitating e-commerce have well-documented effects on consumer behavior and firm organization in the retail sector, but the effects of these new transaction technologies on fiscal systems remain unknown. By extending models of commodity tax competition to include urban spatial structure (agglomeration) and online commerce, one can analyze strategic tax-policy interactions among neighboring localities. Consumers buy different types of commodities, sold either by traditional or by online vendors. When the cost of online shopping falls, we show that equilibrium tax rates and revenues increase in small jurisdictions and decrease in large jurisdictions with retail shopping centers. Policy commentators warn that e-commerce erodes tax revenue - true enough for some localities - but, more accurately, changing transaction costs can generate entirely new commercial and fiscal equilibria that ultimately "redistribute" tax revenues from localities with concentrations of traditional vendors toward other, typically smaller, localities.

In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by beta-secretase to generate a 99-aa C-terminal fragment (C99) that is then cleaved by c-secretase to generate the beta-amyloid (Ab) found in senile plaques. In previous reports, we and others have shown that c-secretase activity is enriched in mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) and that ER-mitochondrial connectivity and MAM function are upregulated in AD. We now show that C99, in addition to its localization in endosomes, can also be found in MAM, where it is normally processed rapidly by c-secretase. In cell models of AD, however, the concentration of unprocessed C99 increases in MAM regions, resulting in elevated sphingolipid turnover and an altered lipid composition of both MAM and mitochondrial membranes. In turn, this change in mitochondrial membrane composition interferes with the proper assembly and activity of mitochondrial respiratory supercomplexes, thereby likely contributing to the bioenergetic defects characteristic of AD. We thank Drs. Orian Shirihai and Marc Liesa (UCLA) for assistance with the Seahorse measurements, Dr. Huaxi Xu (Sanford Burnham Institute) for the APP-DKO MEFs and Dr. Mark Mattson (NIH) for the PS1 knock-in mice, Drs. Arancio and Teich for the APP-KO mice tissues used in these studies, Dr. Hua Yang (Columbia University) for mouse husbandry, and Drs. Marc Tambini, Ira Tabas, and Serge Przedborski for helpful comments. This work was supported by the Fundacion Alfonso Martin Escudero (to M.P.); the Alzheimer's Drug Discovery Foundation, the Ellison Medical Foundation, the Muscular Dystrophy Association, the U.S. Department of Defense W911NF-12-1-9159 and W911F-15-1-0169), and the J. Willard and Alice S. Marriott Foundation (to E.A.S.); the U.S. National Institutes of Health (P01-HD080642 and P01-HD032062 to E.A.S.; NS071571 and HD071593 to M.F.M.; R01-NS056049 and P50-AG008702 to G.D.P.; 1S10OD016214-01A1 to G.S.P. and F.P.M, and K01-AG045335 to E.A.-G.), the Lucien Cote Early Investigator Award in Clinical Genetics from the Parkinson's Disease Foundation (PDF-CEI-1364 and PDF-CEI-1240) to C.G.-L., and National Defense Science and Engineering Graduate Fellowship (FA9550-11-C-0028) to R.R.A. Sí

Medical writing teams are crucial in the pharmaceutical industry at every stage of drug development. With growing regulatory pressure and shrinking profit margins, outsourcing these activities is considered a viable option that provides multiple advantages such as high-quality documents produced in a shorter time and at a lower cost. Correct identification of an outsourcing partner is critical for success. We propose the following eight key criteria that a sponsor company should consider when choosing a medical writing service provider: types of services offered, organisational structure of the provider, resources, quality of services, communication, client relationship, contract, and cost-effectiveness.

Myelin formation has been identified as a modulator of neural plasticity. New tools are required to investigate the mechanisms by which environmental inputs and neural activity regulate myelination patterns. In this study, we demonstrate a microfluidic compartmentalized culture system with integrated electrical stimulation capabilities that can induce neural activity by whole cell and focal stimulation. A set of electric field simulations was performed to confirm spatial restriction of the electrical input in the compartmentalized culture system. We further demonstrate that electrode localization is a key consideration for generating uniform the stimulation of neuron and oligodendrocytes within the compartments. Using three configurations of the electrodes we tested the effects of subcellular activation of neural activity on distal axon myelination with oligodendrocytes. We further investigated if oligodendrocytes have to be exposed to the electrical field to induce axon myelination. An isolated stimulation of cell bodies and proximal axons had the same effect as an isolated stimulation of distal axons co-cultured with oligodendrocytes, and the two modes had a non-different result than whole cell stimulation. Our platform enabled the demonstration that electrical stimulation enhances oligodendrocyte maturation and myelin formation independent of the input localization and oligodendrocyte exposure to the electrical field.

This paper focuses on extending drug release duration from contact lenses by incorporating catanionic aggregates. The aggregates consist of a long-chain cationic surfactant, i.e., cetalkonium chloride (CKC), and an oppositely charged anti-inflammatory amphiphilic drug. We studied three non-steroidal anti-inflammatory (NSAID) drugs with different octanol&ndash, water partition coefficients, diclofenac sodium (DFNa), flurbiprofen sodium (FBNa), and naproxen sodium (NPNa). Confirmation of catanionic aggregate formation in solution was determined by steady and dynamic shear rheology measurements. We observed the increased viscosity, shear thinning, and viscoelastic behavior characteristic of wormlike micelles, the rheological data are reasonably well described using a Maxwellian fluid model with a single relaxation time. In vitro release experiments demonstrated that the extension in the drug release time is dependent on the ability of a drug to form viscoelastic catanionic aggregates. Such aggregates retard the diffusive transport of drug molecules from the contact lenses. Our study revealed that the release kinetics depends on the CKC concentration and the alkyl chain length of the cationic surfactant. We demonstrated that more hydrophobic drugs such as diclofenac sodium show a more extended release than less hydrophobic drugs such as naproxen sodium.

Woman constitutes the family, which leads to society and Nation. Social and economic development of women is necessary for overall economic development of any society or a country. Entrepreneurship is the state of mind which every woman has in her but has not been capitalized in India in way in which it should be. Due to change in environment, now people are more comfortable to accept leading role of women in our society, though there are some exceptions.

The adsorption of fluoride, from a fluoride, contaminated groundwater sample from the village, Bhooma Chota, District Sikar, in the State of Rajasthan, India, has been studied using alumina grade DF-101. The fluoride adsorption capacity (q1) has been fitted into the pseudo-first-order adsorption, pseudo-second-order adsorption, Elovich, and intraparticle diffusion models. It has been found that the kinetic data fits best in the pseudo-second-order rate equation giving a very high correlation coefficient (R2 = 0.991). the modeled fluoride absorption capacity (q1) has been calculated from the various equations using the constants derived from the least square regression plots. The calculated q1 values, model the experimental data very well, for the pseudo-second-order and Elovich equations, as is evident from the sum of square error calculations. Fluoride removal is through a combination of surface absorption and intraparticle diffusion. A study of the fluoride removal process with increasing dosage of activated alumina reveals that though the percentage of fluoride removal increases with activated alumina, the adsorption capacity at equilibrium decreases. The minimum dosage of activated alumina which causes the maximum percentage removal of fluoride from water, while at the same time brings forth its highest equilibrium absorption capacity has been determined.