Small molecular decoys in Alzheimer's disease

Recent progress in the treatment of Alzheimer’s disease(AD)using antibodies against amyloid sustains amyloid generation as a key process in AD.Amyloid formation starts with two amyloidbeta(Aβ)molecules interacting(dimer formation)followed by an accelerating build-up of socalled protofibrils,which turn into fibrils,which accumulate in the characteristic plaques.

Aftershock sequence simulations using synthetic earthquakes and rate-state seismicity formulation

We use an efficient earthquake simulator that incorporates rate-state constitutive properties and uses boundary element method to discretize the fault surfaces, to generate the synthetic earthquakes in the fault system. Rate-and-state seismicity equation is subsequently employed to calculate the seismicity rate in a region of interest using the Coulomb stress transfer from the main shocks in the fault system. The Coulomb stress transfer is obtained by resolving the induced stresses due to the fault patch slips onto the optimal-oriented fault planes. The example results show that immediately after a main shock the aftershocks are concentrated in the vicinity of the rupture area due to positive stress transfers and then dis- perse away into the surrounding region toward the back- ground rate distribution. The number of aftershocks near the rupture region is found to decay with time as Omori aftershock decay law predicts. The example results dem- onstrate that the rate-and-state fault system earthquakesimulator and the seismicity equations based on the rate- state friction nucleation of earthquake are well posited to characterize the aftershock distribution in regional assess- ments of earthquake probabilities.

Search of inhibitors of aldose reductase for treatment of diabetic cataracts using machine learning

Purpose:Patients with diabetes mellitus have an elevated chance of developing cataracts,a degenerative visionimpairing condition often needing surgery.The process of the reduction of glucose to sorbitol in the lens of the human eye that causes cataracts is managed by the Aldose Reductase Enzyme(AR),and it is been found that AR inhibitors may mitigate the onset of diabetic cataracts.There exists a large pool of natural and synthetic AR inhibitors that can prevent diabetic complications,and the development of a machine-learning(ML)prediction model may bring new AR inhibitors with better characteristics into clinical use.Methods:Using known AR inhibitors and their chemical-physical descriptors we created the ML model for prediction of new AR inhibitors.The predicted inhibitors were tested by computational docking to the binding site of AR.Results:Using cross-validation in order to find the most accurate ML model,we ended with final cross-validation accuracy of 90%.Computational docking testing of the predicted inhibitors gave a high level of correlation between the ML prediction score and binding free energy.Conclusions:Currently known AR inhibitors are not used yet for patients for several reasons.We think that new predicted AR inhibitors have the potential to possess more favorable characteristics to be successfully implemented after clinical testing.Exploring new inhibitors can improve patient well-being and lower surgical complications all while decreasing long-term medical expenses.

The GEON service-oriented architecture for Earth Science applications

The Geosciences Network(GEON)project has been developing cyberinfrastructure for data sharing in the Earth Science community based on a serviceoriented architecture.The layered architecture consists of Core,Middleware,and Applications services.Core services provide system-level functions(e.g.user authentication),Middleware services provide generic capabilities(e.g.catalog search),and Application services provide functions that users directly interact with,including applications that are specific to Earth Sciences.The GEON‘service stack’includes a standardized set of these services and the corresponding software modules.The GEON Portal provides Web-based access to these services via a set of portlets.This service-oriented approach has enabled GEON to expand to new partner sites and leverage GEON services for other projects.To facilitate interoperation in a distributed geoinformatics environment,GEON is focusing on standards for distributed search across federated catalogs.

Towards the Tipping Point for FAIR Implementation

This article explores the global implementation of the FAIR Guiding Principles for scientific management and data stewardship,which provide that data should be findable,accessible,interoperable and reusable.The implementation of these principles is designed to lead to the stewardship of data as FAIR digital objects and the establishment of the Internet of FAIR Data and Services(IFDS).If implementation reaches a tipping point,IFDS has the potential to revolutionize how data is managed by making machine and human readable data discoverable for reuse.Accordingly,this article examines the expansion of the implementation of FAIR Guiding Principles,especially how and in which geographies(locations)and areas(topic domains)implementation is taking place.A literature review of academic articles published between 2016 and 2019 on the use of FAIR Guiding Principles is presented.The investigation also includes an analysis of the domains in the IFDS Implementation Networks(INs).Its uptake has been mainly in the Western hemisphere.The investigation found that implementation of FAIR Guiding Principles has taken firm hold in the domain of bio and natural sciences.To achieve a tipping point for FAIR implementation,it is now time to ensure the inclusion of non-European ascendants and of other scientific domains.Apart from equal opportunity and genuine global partnership issues,a permanent European bias poses challenges with regard to the representativeness and validity of data and could limit the potential of IFDS to reach across continental boundaries.The article concludes that,despite efforts to be inclusive,acceptance of the FAIR Guiding Principles and IFDS in different scientific communities is limited and there is a need to act now to prevent dampening of the momentum in the development and implementation of the IFDS.It is further concluded that policy entrepreneurs and the GO FAIR INs may contribute to making the FAIR Guiding Principles more flexible in including different research epistemologies,especially through its GO CHANGE pillar.

FAIR Practices in Africa

This article investigates expansion of the Internet of FAIR Data and Services(IFDS)to Africa,through the three GO FAIR pillars:GO CHANGE,GO BUILD and GO TRAIN.Introduction of the IFDS in Africa has a focus on digital health.Two examples of introducing FAIR are compared:a regional initiative for digital health by governments in the East Africa Community(EAC)and an initiative by a local health provider(Solidarmed)in collaboration with Great Zimbabwe University in Zimbabwe.The obstacles to introducing FAIR are identified as underrepresentation of data from Africa in IFDS at this moment,the lack of explicit recognition of situational context of research in FAIR at present and the lack of acceptability of FAIR as a foreign and European invention which affects acceptance.It is envisaged that FAIR has an important contribution to solve fragmentation in digital health in Africa,and that any obstacles concerning African participation,context relevance and acceptance of IFDS need to be removed.This will require involvement of African researchers and ICT-developers so that it is driven by local ownership.Assessment of ecological validity in FAIR principles would ensure that the context specificity of research is reflected in the FAIR principles.This will help enhance the acceptance of the FAIR Guidelines in Africa and will help strengthen digital health research and services.

FAIR Principles:Interpretations and Implementation Considerations

The FAIR principles have been widely cited,endorsed and adopted by a broad range of stakeholders since their publication in 2016.By intention,the 15 FAIR guiding principles do not dictate specific technological implementations,but provide guidance for improving Findability,Accessibility,Interoperability and Reusability of digital resources.This has likely contributed to the broad adoption of the FAIR principles,because individual stakeholder communities can implement their own FAIR solutions.However,it has also resulted in inconsistent interpretations that carry the risk of leading to incompatible implementations.Thus,while the FAIR principles are formulated on a high level and may be interpreted and implemented in different ways,for true interoperability we need to support convergence in implementation choices that are widely accessible and(re)-usable.We introduce the concept of FAIR implementation considerations to assist accelerated global participation and convergence towards accessible,robust,widespread and consistent FAIR implementations.Any self-identified stakeholder community may either choose to reuse solutions from existing implementations,or when they spot a gap,accept the challenge to create the needed solution,which,ideally,can be used again by other communities in the future.Here,we provide interpretations and implementation considerations(choices and challenges)for each FAIR principle.

Mediating among GeoSciML resources

Integration of data across multiple independently developed data sources can be challenging due to a variety of heterogeneities that exist across such systems.Data mediation technologies provide approaches for overcoming these heterogeneities.Standards such as Geoscience Markup Language can address some of the heterogeneity issues by providing schema standards which sources can adhere to.This article addresses the issue of semantic heterogeneity across information resources by using domain ontologies and registering schema elements and data values to such ontologies.Registering data to ontologies provides a powerful search and data integration capability across disparate geoscience information resources.

Reconstruction of Pathways Associated with Amino Acid Metabolism in Human Mitochondria

We have used a bioinformatics approach for the identification and reconstruction of metabolic pathways associated with amino acid metabolism in human mitochondria. Human mitochondrial proteins determined by experimental and computational methods have been superposed on the reference pathways from the KEGG database to identify mitochondrial pathways. Enzymes at the entry and exit points for each reconstructed pathway were identified, and mitochondrial solute carrier proteins were determined where applicable. Intermediate enzymes in the mitochondrial pathways were identified based on the annotations available from public databases, evidence in current literature, or our MITOPRED program, which predicts the mitochondrial localization of proteins. Through integration of the data derived from experimental, bibliographical, and computational sources, we reconstructed the amino acid metabolic pathways in human mitochondria, which could help better understand the mitochondrial metabolism and its role in human health.

为高等教育信息化基础设施发展可持续的数据服务:要求和可吸取的经验(英文)

美国加州大学圣迭戈分校(UCSD)的科研信息化基础设施(RCI)项目的目标是在集中存储、主机托管、计算、数据管理、联网和技术服务等方面为师生员工提供长期优质的服务。在2012年9月到2013年2月之间,为了确定数据存储的要求以及工作优先排序,RCI数据服务团队(RCIDS)与多名教师和高级职员进行了一系列访谈。这些采访涉及了圣迭戈分校的29个独立的部门和科研单位,有50个不同的小组参加,共代表了600多名研究人员。这些研究小组的各样数据,从人类基因组序列,海洋天然产物,到宇宙模拟实验,是与全球成千上万用户分享的。根据这些访谈的结果,我们总结了圣迭戈分校研究人员对数据服务的10个要求以及5个现有的挑战与风险。RCIDS提出在一个可持续的商业模式下,首先部署网络附加存储(NAS)数据服务;然后,再通过进一步的讨论以及考虑新兴的云计算技术来确定更长远的服务计划;最后,我们对于建立可持续性的高等教育e-科学基础设施的实施方案,基于云计算的数据服务,以及可吸取的经验教训提供了广泛的讨论。