Requirement of argininosuccinate lyase for systemic nitric oxide production

Nitric oxide (NO) is crucial in diverse physiological and pathological processes. We show that a hypomorphic mouse model of argininosuccinate lyase (encoded by Asl) deficiency has a distinct phenotype of multiorgan dysfunction and NO deficiency. Loss of Asl in both humans and mice leads to reduced NO synthesis, owing to both decreased endogenous arginine synthesis and an impaired ability to use extracellular arginine for NO production. Administration of nitrite, which can be converted into NO in vivo, rescued the manifestations of NO deficiency in hypomorphic Asl mice, and a nitric oxide synthase (NOS)-independent NO donor restored NO-dependent vascular reactivity in humans with ASL deficiency. Mechanistic studies showed that ASL has a structural function in addition to its catalytic activity, by which it contributes to the formation of a multiprotein complex required for NO production. Our data demonstrate a previously unappreciated role for ASL in NOS function and NO homeostasis. Hence, ASL may serve as a target for manipulating NO production in experimental models, as well as for the treatment of NO-related diseases

Towards a comprehensive legal aid system in Bangladesh: the need for early access to legal aid in criminal proceedings

The government-funded legal aid system in Bangladesh has been undergoing development. Bangladesh has guaranteed the right to legal assistance in different laws and particularly in the Legal Aid Services Act (LASA) with specific and greater detail. Moreover, it acceded to the International Covenant on Civil and Political Rights (ICCPR) in 2000. In this context, the purpose of this article is to examine the current practice of the country with respect to the granting of early access to legal aid in criminal proceedings in light of international human rights standards. The article indicates that the prevailing problem of arbitrary arrest and pre-trial detention of those who are living in poverty is a matter of grave concern in Bangladesh. The author, therefore, recommends a mechanism to ensure early access to legal aid in the government-operated legal aid framework, as a fundamental aspect of a comprehensive system, for the protection of the interests of those who have been arrested or detained prior to being interviewed and formally charged of a criminal offence

Laminar flow drag reduction on soft porous media

Abstract While researches have focused on drag reduction of various coated surfaces such as superhydrophobic structures and polymer brushes, the insights tso understand the fundamental physics of the laminar skin friction coefficient and the related drag reduction due to the formation of finite velocity at porous surfaces is still relatively unknown. Herein, we quantitatively investigated the flow over a porous medium by developing a framework to model flow of a Newtonian fluid in a channel where the lower surface was replaced by various porous media. We showed that the flow drag reduction induced by the presence of the porous media depends on the values of the permeability parameter α = L/(MK)1/2 and the height ratio δ = H/L, where L is the half thickness of the free flow region, H is the thickness and K is the permeability of the fiber layer, and M is the ratio of the fluid effective dynamic viscosity μe in porous media to its dynamic viscosity μ. We also examined the velocity and shear stress profiles for flow over the permeable layer for the limiting cases of α → 0 and α → ∞. The model predictions were compared with the experimental data for specific porous media and good agreement was found