Liver-specific knockout of arginase-1 leads to a profound phenotype similar to inducible whole body arginase-1 deficiency

Arginase-1 (Arg1) converts arginine to urea and ornithine in the distal step of the urea cycle in liver. We previously generated a tamoxifen-inducible Arg1 deficient mouse model (Arg1-Cre) that disrupts Arg1 expression throughout the whole body and leads to lethality ≈ 2 weeks after gene disruption. Here, we evaluate if liver-selective Arg1 loss is sufficient to recapitulate the phenotype observed in global Arg1 knockout mice, as well as to gauge the effectiveness of gene delivery or hepatocyte transplantation to rescue the phenotype. Liver-selective Arg1 deletion was induced by using an adeno-associated viral (AAV)-thyroxine binding globulin (TBG) promoter-Cre recombinase vector administered to Arg1 "floxed" mice; Arg1(fl/fl) ). An AAV vector expressing an Arg1-enhanced green fluorescent protein (Arg1-eGFP) transgene was used for gene delivery, while intrasplenic injection of wild-type (WT) C57BL/6 hepatocytes after partial hepatectomy was used for cell delivery to "rescue" tamoxifen-treated Arg1-Cre mice. The results indicate that liver-selective loss of Arg1 (> 90% deficient) leads to a phenotype resembling the whole body knockout of Arg1 with lethality ≈ 3 weeks after Cre-induced gene disruption. Delivery of Arg1-eGFP AAV rescues more than half of Arg1 global knockout male mice (survival > 4 months) but a significant proportion still succumb to the enzyme deficiency even though liver expression and enzyme activity of the fusion protein reach levels observed in WT animals. Significant Arg1 enzyme activity from engrafted WT hepatocytes into knockout livers can be achieved but not sufficient for rescuing the lethal phenotype. This raises a conundrum relating to liver-specific expression of Arg1. On the one hand, loss of expression in this organ appears to be both necessary and sufficient to explain the lethal phenotype of the genetic disorder in mice. On the other hand, gene and cell-directed therapies suggest that rescue of extra-hepatic Arg1 expression may also be necessary for disease correction. Further studies are needed in order to illuminate the detailed mechanisms for pathogenesis of Arg1-deficiency

Connectivity analysis for mmWave V2V networks : exploring critical distance and beam misalignment

In this paper, we investigate the analytical connectivity performance of Vehicle-to-Vehicle communications when using millimeter wave carrier frequencies, by taking into account its challenges of high path loss and beam misalignment. The connectivity analysis is carried out in two dimensions; first, an analytical and parametric critical transmission range is developed, based on system parameters such as vehicle density and Signal-to-Interference-Plus-Noise ratio threshold, and second, the beam misalignment probability caused by the in-lane lateral displacement of vehicles is determined. The analysis is carried out for antennas with half power beamwidths of 3◦, 6◦, 10◦, 20◦ and 45◦, resulting in different beamwidth regimes depending upon road curvature and vehicle density. For low/medium vehicle density on low-curvature roads, the sensitivity of the network connectivity to the beamwidth is relatively small. On the other hand, the narrowest beamwidth is the best performer in terms of maximizing connectivity in low/medium vehicle density scenarios on high-curvature roads, and the wider beamwidth is the best performer for high vehicle density on low-curvature roads

Intrinsically Polar Elastic Metamaterials

In many applications, one needs to combine materials with varying properties to achieve certain functionalities. For example, the inner layer of a helmet should be soft for cushioning while the outer shell should be rigid to provide protection. Over time, these combined materials either separate or wear and tear, risking the exposure of an undesired material property. This work presents a design principle for a material that gains unique properties from its 3D microstructure, consisting of repeating basic building blocks, rather than its material composition. The 3D printed specimens show, at two of its opposing faces along the same axis, different stiffness (i.e., soft on one face and hard on the other). The realized material is protected by design (i.e., topology) against cuts and tears: No matter how material is removed, either layer by layer, or in arbitrary cuts through the repeating building blocks, two opposing faces remain largely different in their mechanical response

Gunrock: GPU Graph Analytics

For large-scale graph analytics on the GPU, the irregularity of data access and control flow, and the complexity of programming GPUs, have presented two significant challenges to developing a programmable high-performance graph library. "Gunrock", our graph-processing system designed specifically for the GPU, uses a high-level, bulk-synchronous, data-centric abstraction focused on operations on a vertex or edge frontier. Gunrock achieves a balance between performance and expressiveness by coupling high performance GPU computing primitives and optimization strategies with a high-level programming model that allows programmers to quickly develop new graph primitives with small code size and minimal GPU programming knowledge. We characterize the performance of various optimization strategies and evaluate Gunrock's overall performance on different GPU architectures on a wide range of graph primitives that span from traversal-based algorithms and ranking algorithms, to triangle counting and bipartite-graph-based algorithms. The results show that on a single GPU, Gunrock has on average at least an order of magnitude speedup over Boost and PowerGraph, comparable performance to the fastest GPU hardwired primitives and CPU shared-memory graph libraries such as Ligra and Galois, and better performance than any other GPU high-level graph library.Comment: 52 pages, invited paper to ACM Transactions on Parallel Computing (TOPC), an extended version of PPoPP'16 paper "Gunrock: A High-Performance Graph Processing Library on the GPU

Inertial amplification of continuous structures: Large band gaps from small masses

Wave motion in a continuous elastic rod with a periodically attached inertial-amplification mechanism is investigated. The mechanism has properties similar to an "inerter" typically used in vehicle suspensions, however here it is constructed and utilized in a manner that alters the intrinsic properties of a continuous structure. The elastodynamic band structure of the hybrid rod-mechanism structure yields band gaps that are exceedingly wide and deep when compared to what can be obtained using standard local resonators, while still being low in frequency. With this concept, a large band gap may be realized with as much as twenty times less added mass compared to what is needed in a standard local resonator configuration. The emerging inertially enhanced continuous structure also exhibits unique qualitative features in its dispersion curves. These include the existence of a characteristic double-peak in the attenuation constant profile within gaps and the possibility of coalescence of two neighbouring gaps creating a large contiguous gap.Comment: Manuscript is under review for journal publicatio

The effect of oil prices on the economic diversification process: evidence from the GCC countries

We investigate the Granger non-causality relationship between oil prices and the economic diversification process in the GCC countries during the period 1989-2017. This paper uses Pedroni's (2004) panel cointegration tests and the panel non-causality test of Dumitrescu-Hurlin (2012) to achieve its goals. We find that oil price changes Granger cause the movements in the diversification progression. It indicates that economic diversification of the GCC countries is not a priority to the GCC governments because their role is changing. As a result, the GCC countries should give priority to the economic diversification if it is a strategic plan for their economies

Deposit Rate and Lending Rate in Jordan, Which leads Which? A Cointegration Analysis

This study intends to investigate empirically the long-run relationship between deposit and lending rates in Jordan by utilizing quarterly data over the period (1994-2010). Empirically, we search to identify the dominant interest rate; either deposit rate or lending rate. To achieve the current study goals, we employ the error correction model technique and the asymmetric short-run dynamic model. The empirical evidence of the Jordanian economy illustrates deposit and lending rates have a long-run relationship. Deposit rate leads lending rate. As a result, the short-run lending rate adjustment for the deviation from the long-run equilibrium by about 22 percent in the current period. In the long-run, lending rate adjusts by 90 percent for a change in deposit rate