Clinical relevance of MTHFR, eNOS, ACE, and ApoE gene polymorphisms and serum vitamin profile among Malay patients with ischemic stroke

Background The purpose of this study was threefold. First, it was to determine the relationship between serum vitamin profiles and ischemic stroke. The second purpose was to investigate the association of methylenetetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and apolipoprotein-E (ApoE) gene polymorphisms with ischemic stroke and further correlate with serum vitamin profiles among ischemic stroke patients. The third purpose of the study was to highlight the interaction of MTHFR and eNOS haplotypes with serum vitamin profiles and ischemic stroke risks. Methods Polymorphisms of these genes were analyzed in age-, sex-, and ethnicity-matched case–controls (n = 594); serum vitamin profiles were determined using immunoassays. Results The MTHFR 677C>T, 1298A>C, eNOS intron 4a/b, and ApoE polymorphisms were significantly associated with the increased risk of ischemic stroke. Elevated serum homocysteine and vitamin B12 levels were associated with MTHFR 677C>T and eNOS intron 4a/b polymorphisms. The ApoE and eNOS −786T>C polymorphisms were associated with increased serum vitamin B12 levels. However, none of the polymorphisms influenced serum folate levels except for the MTHFR 1298A>C. Different patterns of MTHFR and eNOS haplotypes tend to affect serum vitamin profiles to different degrees, which contribute to either different susceptibility risk or protective effect on ischemic stroke. Overall, increased levels of serum homocysteine and vitamin B12 levels were associated with higher risk of ischemic stroke in the investigated population. Conclusions The present study suggests that the genotypes and haplotypes of MTHFR 677C>T and eNOS intron 4a/b polymorphisms are potential serum biomarkers in the pathophysiological processes of ischemic stroke, by modulating homocysteine and vitamin B12 levels.

Two-step self-assembly of hierarchically-ordered nanostructures

Due to their unique size- and shape-dependent physical and chemical properties, highly hierarchically-ordered nanostructures have attracted great attention with a view to application in emerging technologies, such as novel energy generation, harvesting, and storage devices. The question of how to get controllable ensembles of nanostructures, however, still remains a challenge. This concept paper first summarizes and clarifies the concept of the two-step self-assembly approach for the synthesis of hierarchically-ordered nanostructures with complex morphology. Based on the preparation processes, two-step self-assembly can be classified into two typical types, namely, two-step self-assembly with two discontinuous processes and two-step self-assembly completed in one-pot solutions with two continuous processes. Compared to the conventional one-step self-assembly, the two-step self-assembly approach allows the combination of multiple synthetic techniques and the realization of complex nanostructures with hierarchically-ordered multiscale structures. Moreover, this approach also allows the self-assembly of heterostructures or hybrid nanomaterials in a cost-effective way. It is expected that widespread application of two-step self-assembly will give us a new way to fabricate multifunctional nanostructures with deliberately designed architectures. The concept of two-step self-assembly can also be extended to syntheses including more than two chemical/physical reaction steps (multiple-step self-assembly).

Improved photovoltaic performance of dye-sensitized solar cells with modified self-assembling highly ordered mesoporous TiO 2 photoanodes

Strategies for improving the photovoltaic performance of dye-sensitized solar cells (DSSCs) are proposed by modifying highly transparent and highly ordered multilayer mesoporous TiO 2 photoanodes through nitrogen-doping and top-coating with a light-scattering layer. The mesoporous TiO 2 photoanodes were fabricated by an evaporation-induced self-assembly method. In regard to the modification methods, the light-scattering layer as a top-coating was proved to be superior to nitrogen-doping in enhancing not only the power conversion efficiency but also the fill factor of DSSCs. The optimized bifunctional photoanode consisted of a 30-layer mesoporous TiO 2 thin film (4.15 μm) and a Degussa P25 light-scattering top-layer (4 μm), which gives rise to a ∼200% higher cell efficiency than for unmodified cells and a fill factor of 0.72. These advantages are attributed to its higher dye adsorption, better light scattering, and faster photon-electron transport. Such a photoanode configuration provides an efficient way to enhance the energy conversion efficiency of DSSCs.

Nano-confined synthesis of highly ordered mesoporous carbon and its performance as electrode material for electrochemical behavior of riboflavin (vitamin B2) and dopamine

Highly ordered mesoporous carbon (MC) has been synthesized from sucrose, a non-toxic and costeffective source of carbon. X-ray diffraction, N2 adsorption–desorption isotherm and transmission electron micrograph (TEM) were used to characterize the MC. The XRD patterns show the formation of highly ordered mesoporous structures of SBA15 and mesoporous carbon. The N2 adsorptiondesorption isotherms suggest that the MC exhibits a narrow pore-size distribution with high surface area of 1559 m2/g. The potential application of MC as a novel electrode material was investigated using cyclic voltammetry for riboflavin (vitamin B2) and dopamine. MC-modified glassy carbon electrode (MC/GC) shows increase in peak current compared to GC electrode in potassium ferricyanide which clearly suggest that MC/GC possesses larger electrode area (1.8 fold) compared with bare GC electrode. The electrocatalytic behavior of MC/GC was investigated towards the oxidation of riboflavin (vitamin B2) and dopamine using cyclic voltammetry which show larger oxidation current compared to unmodified electrode and thus MC/GC may have the potential to be used as a chemically modified electrode.

Data-aware task scheduling for all-to-all comparison problems in heterogeneous distributed systems

Solving large-scale all-to-all comparison problems using distributed computing is increasingly significant for various applications. Previous efforts to implement distributed all-to-all comparison frameworks have treated the two phases of data distribution and comparison task scheduling separately. This leads to high storage demands as well as poor data locality for the comparison tasks, thus creating a need to redistribute the data at runtime. Furthermore, most previous methods have been developed for homogeneous computing environments, so their overall performance is degraded even further when they are used in heterogeneous distributed systems. To tackle these challenges, this paper presents a data-aware task scheduling approach for solving all-to-all comparison problems in heterogeneous distributed systems. The approach formulates the requirements for data distribution and comparison task scheduling simultaneously as a constrained optimization problem. Then, metaheuristic data pre-scheduling and dynamic task scheduling strategies are developed along with an algorithmic implementation to solve the problem. The approach provides perfect data locality for all comparison tasks, avoiding rearrangement of data at runtime. It achieves load balancing among heterogeneous computing nodes, thus enhancing the overall computation time. It also reduces data storage requirements across the network. The effectiveness of the approach is demonstrated through experimental studies.

Characterization of the carbonic anhydrase gene family and other key osmoregulatory genes in Australian freshwater crayfish (genus Cherax)

Cherax quadricarinatus (Redclaw), C. destructor (Yabby) and C. cainii (Marron) are a group of economically important freshwater crayfish and have been developed for aquaculture production in many countries. As crayfish are farmed in a wide range of culture conditions, optimisation of water quality parameters, are crucial for their maximum growth performance. Previous reports have shown that fluctuations in water quality can negatively impact on growth of crayfish. Therefore, this project aims to identify and characterize the major genes that enable freshwater crayfish to persist in different water chemistries and evaluate their patterns of expression under different water parameters. Overall, this project found a number of candidate genes in all three species and determined that water chemistry had a strong influence on the expression of candidate genes. This information is important in the optimization of water quality parameters in freshwater crayfish aquaculture production.

Neoadjuvant crizotinib in advanced inflammatory myofibroblastic tumour with ALK gene rearrangement

Background Inflammatory myofibroblastic tumours (IMTs) are rare sarcomas that were first described in the lung. They are composed of myofibroblastic mesenchymal spindle cells accompanied by an inflammatory infiltrate of plasma cells. Complete resection is the treatment of choice. There is currently no standard treatment for inoperable or recurrent disease. Expression of ALK protein triggered by ALK gene rearrangement at chromosome 2p23 has been found in 36%-60% of IMTs. Case report We report a rapid early response to crizotinib as neoadjuvant therapy, enabling surgical excision of a large ALK-translocated IMT, which resulted in complete disease clearance. To the best of our knowledge, this is the first case in the literature of a patient with IMT in whom crizotinib was used successfully in the neoadjuvant or curative setting.

First-Line afatinib versus chemotherapy in patients with non–small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases

Introduction Metastatic spread to the brain is common in patients with non–small cell lung cancer (NSCLC), but these patients are generally excluded from prospective clinical trials. The studies, phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations (LUX-Lung 3) and a randomized, open-label, phase III study of BIBW 2992 versus chemotherapy as first-line treatment for patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR activating mutation (LUX-Lung 6) investigated first-line afatinib versus platinum-based chemotherapy in epidermal growth factor receptor gene (EGFR) mutation-positive patients with NSCLC and included patients with brain metastases; prespecified subgroup analyses are assessed in this article. Methods For both LUX-Lung 3 and LUX-Lung 6, prespecified subgroup analyses of progression-free survival (PFS), overall survival, and objective response rate were undertaken in patients with asymptomatic brain metastases at baseline (n = 35 and n = 46, respectively). Post hoc analyses of clinical outcomes was undertaken in the combined data set (n = 81). Results In both studies, there was a trend toward improved PFS with afatinib versus chemotherapy in patients with brain metastases (LUX-Lung 3: 11.1 versus 5.4 months, hazard ratio [HR] = 0.54, p = 0.1378; LUX-Lung 6: 8.2 versus 4.7 months, HR = 0.47, p = 0.1060). The magnitude of PFS improvement with afatinib was similar to that observed in patients without brain metastases. In combined analysis, PFS was significantly improved with afatinib versus with chemotherapy in patients with brain metastases (8.2 versus 5.4 months; HR, 0.50; p = 0.0297). Afatinib significantly improved the objective response rate versus chemotherapy in patients with brain metastases. Safety findings were consistent with previous reports. Conclusions These findings lend support to the clinical activity of afatinib in EGFR mutation–positive patients with NSCLC and asymptomatic brain metastases.