NOX Inhibitors - A Promising Avenue for Ischemic Stroke.

NADPH-oxidase (NOX) mediated superoxide originally found on leukocytes, but now recognized in several types of cells in the brain. It has been shown to play an important role in the progression of stroke and related cerebrovascular disease. NOX is a multisubunit complex consisting of 2 membrane-associated and 4 cytosolic subunits. NOX activation occurs when cytosolic subunits translocate to the membrane, leading to transport electrons to oxygen, thus producing superoxide. Superoxide produced by NOX is thought to function in long-term potentiation and intercellular signaling, but excessive production is damaging and has been implicated to play an important role in the progression of ischemic brain. Thus, inhibition of NOX activity may prove to be a promising treatment for ischemic brain as well as an adjunctive agent to prevent its secondary complications. There is mounting evidence that NOX inhibition in the ischemic brain is neuroprotective, and targeting NOX in circulating immune cells will also improve outcome. This review will focus on therapeutic effects of NOX assembly inhibitors in brain ischemia and stroke. However, the lack of specificity and toxicities of existing inhibitors are clear hurdles that will need to be overcome before this class of compounds could be translated clinically

Enucleation after Embolization of Liver Failure-Causing Giant Liver Hemangioma

Patient: Female, 73 Final Diagnosis: Giant liver hemangioma Symptoms: Abdominal discomfort • abdominal enlargement • Icterus Medication: — Clinical Procedure: Enucleation after embolization of liver failure-causing giant liver Specialty: Surgery Objective: Unusual clinical course Background: Hepatic hemangioma is a congenital tumor of the mesenchymal tissues of the liver. While typically benign, these tumors can occasionally grow to sufficient size to cause a number of symptoms, including pain, severe hepatic dysfunction, or, rarely, consumptive coagulopathy. In such instances, surgical treatment may be warranted. Case Report: We present a case of a symptomatic giant hepatic hemangioma in an elderly patient who presented with impending liver failure. She was successfully treated with a combination of surgical enucleation and liver resection after preoperative arterial embolization. We also provide a brief discussion of current treatment options for giant hepatic hemangiomas. Conclusions: Early referral to experienced surgical centers before the onset of dire complications such as severe hepatic dysfunction and liver failure is recommended

An Idealist\u27s Journey: George Clayton Foulk and U.S.-Korea Relations, 1883-1887

This senior thesis studies the character and influence of a young American naval officer and diplomat. George Clayton Foulk, the 1st Naval Attaché to the United States Legation and the 2nd U.S. Minister to Korea, brought his intellectual ability and passion to this East Asian country. He hoped for Korea to become an independent, modernized state. Due to the strong Chinese opposition and lack of assistance from the U.S. government, Foulk failed to realize his dream and left Korea in disgrace. However, his service instilled a positive image of America in the minds of many Koreans. By closely examining his letters and journals, this thesis brings an image of a cosmopolitan who expressed genuine understanding of and sympathy for Korea. More importantly, this thesis introduces his vision that America must become an exceptional country which spreads its values across the world through peaceful means. Even today, the clash between Foulk’s idealism and the realpolitik of Washington policymakers raises a question on the future of American diplomacy

Herman Bavinck between scholastic and modern psychology: toward a reformed psychology.

Bavinck completed his first psychology book, Principles of Psychology (Beginselen der Psychologie, 1897) in the middle of his theological writings from his interaction with the nineteenth century psychologies. In 1920, Bavinck published another psychology book entitled Biblical and Religious Psychology (Bijbelsche en Religieuze Psychologie) on the basis of solid exegesis and biblical principles. In Principles of Psychology, Bavinck intended that his psychological principles would be as worthy as the empirical psychology of his day. Kuyper also stressed the doctrinal value of faculty psychology to Bavinck’s first psychology book in his review. Yet, these two psychology books were virtually neglected both in the field of psychology and in Reformed anthropology. What is more, scholars like Hepp and Jaarsma demonstrated that in his later years Bavinck rejected the scholastic faculty psychology defended in his first psychology book. It, however, is shown that Bavinck does not change his views on faculty psychology, but elaborates on the doctrine of faculties for a more integrated view of the soul, even while interacting with the modern psychology of his day. Throughout his writings, Bavinck consistently advocates the unity of the soul in a more balanced way by presenting the supremacy of the heart, the central organ of all human faculties. Beyond scholastic psychology, Bavinck also properly embraces the new ideas of nineteenth century psychologies like the unconsciousness theory, the psychology of religion, and child psychology

The Effect Of The Relationships Between Affiliated Firms On Direction Of Income Shifting Within Business Groups

In this study, we examined how income shifting performs among affiliates in a business group to maximize the benefits of the entire business group in terms of minimizing the tax burden, with a particular focus on the direction of income shifting between affiliates within the business group. We find that tax-related decision-making for the entire business group is affected by the relationships between the affiliated firms, that is, the ownership structure of the whole business group. To analyze the ownership structure, we use centrality measures in a social network analysis. The results show that affiliates with the higher outdegree-centrality; that is, firms investing more shareholdings in other affiliates have a tendency to perform more income shifting. On the other hand, the affiliates with high indegree-centrality, that is, firms which are owned by other affiliates, were revealed to be given the income shifting from other affiliated firms to minimize the tax burden of the entire business group

Quantitative Shotgun Proteomics Analysis of Rice Anther Proteins after Exposure to High Temperature

In rice, the stage of development most sensitive to high temperature stress is flowering, and exposure at this stage can result in spikelet sterility, thereby leading to significant yield losses. In this study, protein expression patterns of rice anthers from Dianxi4, a high temperature tolerant Japonica rice variety, were compared between samples exposed to high temperature and those grown in natural field conditions in Korea. Shotgun proteomics analysis of three replicate control and high-temperature-treated samples identified 3,266 nonredundant rice anther proteins (false discovery rate < 0.01). We found that high levels of ATP synthase, cupin domain-containing proteins, and pollen allergen proteins were present in rice anthers. Comparative analyses of 1,944 reproducibly expressed proteins identified 139 differentially expressed proteins, with 95 increased and 44 decreased in response to high temperature conditions. Heat shock, DnaK family, and chaperone proteins showed highly increased expression, suggesting that the high temperature tolerance of Dianxi4 is achieved by stabilization of proteins in pollen cells. Trehalose synthase was also highly increased after heat treatment, suggesting a possible role for trehalose in preventing protein denaturation through desiccation

Developing eThread pipeline using SAGA-pilot abstraction for large-scale structural bioinformatics

While most of computational annotation approaches are sequence-based, threading methods are becoming increasingly attractive because of predicted structural information that could uncover the underlying function. However, threading tools are generally compute-intensive and the number of protein sequences from even small genomes such as prokaryotes is large typically containing many thousands, prohibiting their application as a genome-wide structural systems biology tool. To leverage its utility, we have developed a pipeline for eThread - a meta-threading protein structure modeling tool, that can use computational resources efficiently and effectively. We employ a pilot-based approach that supports seamless data and task-level parallelism and manages large variation in workload and computational requirements. Our scalable pipeline is deployed on Amazon EC2 and can efficiently select resources based upon task requirements. We present runtime analysis to characterize computational complexity of eThread and EC2 infrastructure. Based on results, we suggest a pathway to an optimized solution with respect to metrics such as time-to-solution or cost-to-solution. Our eThread pipeline can scale to support a large number of sequences and is expected to be a viable solution for genome-scale structural bioinformatics and structure-based annotation, particularly, amenable for small genomes such as prokaryotes. The developed pipeline is easily extensible to other types of distributed cyberinfrastructure. © 2014 Anjani Ragothaman et al

MapReduce-based RESTMD: Enabling Large-scale Sampling Tasks With Distributed HPC Systems

A novel implementation of Replica Exchange Statistical Temperature Molecular Dynamics (RESTMD), belonging to a generalized ensemble method and also known as parallel tempering, is presented. Our implementation employs the MapReduce (MR)-based iterative framework for launching RESTMD over high performance computing (HPC) clusters including our test bed system, Cyber-infrastructure for Reconfigurable Optical Networks (CRON) simulating a network-connected distributed system. Our main contribution is a new implementation of STMD plugged into the well-known CHARMM molecular dynamics package as well as the RESTMD implementation powered by the Hadoop that scales out in a cluster and across distributed systems effectively. To address challenges for the use of Hadoop MapReduce, we examined contributing factors on the performance of the proposed framework with various runtime analysis experiments with two biological systems that differ in size and over different types of HPC resources. Many advantages with the use of RESTMD suggest its effectiveness for enhanced sampling, one of grand challenges in a variety of areas of studies ranging from chemical systems to statistical inference. Lastly, with its support for scale-across capacity over distributed computing infrastructure (DCI) and the use of Hadoop for coarse-grained task-level parallelism, MapReduce-based RESTMD represents truly a good example of the next-generation of applications whose provision is increasingly becoming demanded by science gateway projects, in particular, backed by IaaS clouds. © 2014 IEEE

Enabling Large-Scale Biomolecular Conformation Search With Replica Exchange Statistical Temperature Molecular Dynamics (RESTMD) Over HPC And Cloud Computing Resources

We present the latest development and experimental simulation studies of Statistical Temperature Molecular Dynamics (STMD) and its parallel tempering version, Replica Exchange Statistical Temperature Molecular Dynamics (RESTMD). Our main contributions are i) introduction of newly implemented STMD in LAMMPS, ii) use of large scale distributed cyber infrastructure including Amazon EC2 and the nationwide distributed computing infrastructure GENI, in addition to High-performance Computing (HPC) cluster systems, and iii) benchmark and simulation results highlighting advantages and potentials of STMD and RESTMD for challenging large-scale bio molecular conformational search. In this work, we attempt to provide convincing evidence that RESTMD, combining two advanced sampling protocols, STMD and the replica exchange algorithm, offers various advantages over not only conventional ineffective approaches but also other enhanced sampling methods. Interestingly, RESTMD has benefits over the most popular Replica Exchange Molecular Dynamics (REMD) as an application maximizing its capacity in HPC environments. For example, RESTMD alleviates the need of a large number of replicas which is unavoidable in REMD and is flexible in order to exploit the maximum amount of available computing power of a cluster system. Continuing our recent effort in which RESTMD was implemented with a community molecular dynamics package, CHARMM, and the Hadoop MapReduce, in this work, we report latest development outcomes. First of all, we plugged the implementation of STMD into LAMMPS, one of the most popular public molecular dynamics packages. This is expected to position STMD and RESTMD appealing to investigators from a broad range of life science fields. Secondly, Hadoop MapReduce-based RESTMD is now able to run on Amazon EC2 and the nationwide network virtual organization, the GENI distributed computing environment. Thirdly, in order to find optimized parameters for RESTMD simulations, simulation results using test systems, water and solvated cram bin, were obtained and presented. These results, despite of relatively small sizes and short time scale trajectories, serve to underscore merits and potentials of STMD and RESTMD with respect to the strength in algorithmic advantages as well as efficient utilization of distributed resources