Effect of Alkyl Chain Length and Linker Atom on the Crystal Packing in 6,12-Dialkoxy- And 6,12-Dialkylsulfanyl-Benzo[1,2- b:4,5- b′]bis[ b]benzothiophenes

The effect of varying the chain length on the solid state conformation and packing of 6,12-dialkoxy- and 6,12-dialkylsulfanyl-benzo[1,2-b:4,5-b′]bis[b]benzothiophenes has been studied. The compounds were prepared by SNAr reaction of 6,12-difluorbenzo[1,2-b:4,5-b′]bis[b]benzothiophene with alkoxides or alkanethiolates derived from C7-C10 alcohols and alkanethiols. Single crystal X-ray diffraction analysis revealed that all but two compounds crystallize in the triclinic space group P1. Two compounds were obtained as monoclinic crystals with space group P21/c. The alkoxy substituted compounds adopted a molecular conformation with a step from the core and a gauche conformation about the C1′-C2′ bond placing the alkyl chains close to parallel with the pentacyclic arene ring system, whereas in the alkylsufanyl derivatives, the alkyl chains were arranged strongly deviated from the plane of the ring, with the sulfur atom antiperiplanar to C3′ of the alkyl chain. NMR measurement of T1 relaxation in CDCl3 showed both the alkoxy and alkylsulfanyl substituents to be freely rotating at ambient temperature in solution, indicating the orientation of the chains in the solid state was due to packing interactions during crystallization

Chronic cerebral hypoperfusion alters amyloid-β peptide pools leading to cerebral amyloid angiopathy, microinfarcts and hemorrhages in Tg-SwDI mice

Cerebral hypoperfusion is an early feature of Alzheimer’s disease (AD) that influences the progression from mild cognitive impairment to dementia. Understanding the mechanism is of critical importance in the search for new effective therapies. We hypothesized that cerebral hypoperfusion promotes the accumulation of amyloid-β (Aβ) and degenerative changes in the brain and is a potential mechanism contributing to development of dementia. To address this, we studied the effects of chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis on Aβ peptide pools in a transgenic mouse model of AD (transgenic mice with Swedish, Dutch and Iowa mutations in human amyloid precursor protein (APP) (Tg-SwDI)). Cerebrovascular integrity was characterized by quantifying the occurrence of microinfarcts and haemorrhages and compared with wild-type mice without Aβ. A significant increase in soluble Aβ peptides (Aβ40/42) was detected after 1 month of hypoperfusion in the parenchyma in parallel with elevated APP and APP proteolytic products. Following 3 months, a significant increase in insoluble Aβ40/42 was determined in the parenchyma and vasculature. Microinfarct load was significantly increased in the Tg-SwDI as compared with wild-type mice and further exacerbated by hypoperfusion at 1 and 3 months. In addition, the number of Tg-SwDI hypoperfused mice with haemorrhages was increased compared with hypoperfused wild-type mice. Soluble parenchymal Aβ was associated with elevated NADPH oxidase-2 (NOX2) which was exacerbated by 1-month hypoperfusion. We suggest that in response to hypoperfusion, increased Aβ production/deposition may contribute to degenerative processes by triggering oxidative stress promoting cerebrovascular disruption and the development of microinfarcts.</jats:p

Advancing Cyberinfrastructure to support high resolution water resources modeling (Invited)

Addressing the problem of how the availability and quality of water resources at large scales are sensitive to climate variability, watershed alterations and management activities requires computational resources that combine data from multiple sources and support integrated modeling. Related cyberinfrastructure challenges include: 1) how can we best structure data and computer models to address this scientific problem through the use of high-performance and data-intensive computing, and 2) how can we do this in a way that discipline scientists without extensive computational and algorithmic knowledge and experience can take advantage of advances in cyberinfrastructure? This presentation will describe a new system called CI-WATER that is being developed to address these challenges and advance high resolution water resources modeling in the Western U.S. We are building on existing tools that enable collaboration to develop model and data interfaces that link integrated system models running within an HPC environment to multiple data sources. Our goal is to enhance the use of computational simulation and data-intensive modeling to better understand water resources. Addressing water resource problems in the Western U.S. requires simulation of natural and engineered systems, as well as representation of legal (water rights) and institutional constraints alongside the representation of physical processes. We are establishing data services to represent the engineered infrastructure and legal and institutional systems in a way that they can be used with high resolution multi-physics watershed modeling at high spatial resolution. These services will enable incorporation of location-specific information on water management infrastructure and systems into the assessment of regional water availability in the face of growing demands, uncertain future meteorological forcings, and existing prior-appropriations water rights. This presentation will discuss the informatics challenges involved with data management and easy-to-use access to high performance computing being tackled in this project

Recent advances in drug discovery for diabetic kidney disease

Introduction: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD), and 40% of patients with diabetes develop DKD. Although some pathophysiological mechanisms and drug targets of DKD have been described, the effectiveness or clinical usefulness of such treatment has not been well validated. Therefore, searching for new targets and potential therapeutic candidates has become an emerging research area. Areas covered: The pathophysiological mechanisms, new drug targets and potential therapeutic compounds for DKD are addressed in this review. Expert opinion: Although preclinical and clinical evidence has shown some positive results for controlling DKD progression, treatment regimens have not been well developed to reduce the mortality in patients with DKD globally. Therefore, the discovery of new therapeutic targets and effective target-based drugs to achieve better and safe treatment are urgently required. Preclinical screening and clinical trials for such drugs are needed

Pillared two-dimensional metal-organic frameworks based on a lower-rim acid appended calix[4]arene

Solvothermal reactions of the lower-rim functionalized diacid calix[4]arene 25,27-bis(methoxycarboxylic acid)-26,28-dihydroxy-4-tert-butylcalix[4]arene (LH₂) with Zn(NO₃)₂•6H₂O and the dipyridyl ligands 4,4/-bipyridyl (4,4/-bipy), 1,2-di(4-pyridyl)ethylene (DPE) or 4,4/-azopyridyl (4,4/-azopy) afforded a series of 2-D structures of the formulae {[Zn(4,4/-bipy)(L)]•2¼DEF}n (1), {[Zn₂(L)(DPE)]•DEF}n (2) and {[Zn(OH₂)₂(L)(4,4/-azopy)]•DEF}n (3) (DEF = diethylformamide)

A user-friendly database of coastal flooding in the United Kingdom from 1915–2014

Coastal flooding caused by extreme sea levels can be devastating, with long-lasting and diverse consequences. Historically, the UK has suffered major flooding events, and at present 2.5 million properties and £150 billion of assets are potentially exposed to coastal flooding. However, no formal system is in place to catalogue which storms and high sea level events progress to coastal flooding. Furthermore, information on the extent of flooding and associated damages is not systematically documented nationwide. Here we present a database and online tool called ‘SurgeWatch’, which provides a systematic UK-wide record of high sea level and coastal flood events over the last 100 years (1915-2014). Using records from the National Tide Gauge Network, with a dataset of exceedance probabilities and meteorological fields, SurgeWatch captures information of 96 storms during this period, the highest sea levels they produced, and the occurrence and severity of coastal flooding. The data are presented to be easily assessable and understandable to a range of users including, scientists, coastal engineers, managers and planners and concerned citizens

A Resource Centric Approach For Advancing Collaboration Through Hydrologic Data And Model Sharing

HydroShare is an online, collaborative system being developed for open sharing of hydrologic data and models. The goal of HydroShare is to enable scientists to easily discover and access hydrologic data and models, retrieve them to their desktop or perform analyses in a distributed computing environment that may include grid, cloud or high performance computing model instances as necessary. Scientists may also publish outcomes (data, results or models) into HydroShare, using the system as a collaboration platform for sharing data, models and analyses. HydroShare is expanding the data sharing capability of the CUAHSI Hydrologic Information System by broadening the classes of data accommodated, creating new capability to share models and model components, and taking advantage of emerging social media functionality to enhance information about and collaboration around hydrologic data and models. One of the fundamental concepts in HydroShare is that of a Resource. All content is represented using a Resource Data Model that separates system and science metadata and has elements common to all resources as well as elements specific to the types of resources HydroShare will support. These will include different data types used in the hydrology community and models and workflows that require metadata on execution functionality. The HydroShare web interface and social media functions are being developed using the Drupal content management system. A geospatial visualization and analysis component enables searching, visualizing, and analyzing geographic datasets. The integrated Rule-Oriented Data System (iRODS) is being used to manage federated data content and perform rule-based background actions on data and model resources, including parsing to generate metadata catalog information and the execution of models and workflows. This presentation will introduce the HydroShare functionality developed to date, describe key elements of the Resource Data Model and outline the roadmap for future development

Quantitative Trait Locus Analysis of Mating Behavior and Male Sex Pheromones in Nasonia Wasps.

A major focus in speciation genetics is to identify the chromosomal regions and genes that reduce hybridization and gene flow. We investigated the genetic architecture of mating behavior in the parasitoid wasp species pair Nasonia giraulti and Nasonia oneida that exhibit strong prezygotic isolation. Behavioral analysis showed that N. oneida females had consistently higher latency times and broke off the mating sequence more often in the mounting stage when confronted with N. giraulti males compared with males of their own species. N. oneida males produce a lower quantity of the long-range male sex pheromone, (4R,5S)-5-hydroxy-4-decanolide (RS-HDL). Crosses between the two species yielded hybrid males with various pheromone quantities and these males were used in mating trials with females of either species to measure female mate discrimination rates. A quantitative trait locus (QTL) analysis involving 475 recombinant hybrid males (F2), 2148 reciprocally backcrossed females (F3), and a linkage map of 52 equally spaced neutral single nucleotide polymorphism (SNP) markers plus SNPs in 40 candidate mating behavior genes revealed four QTL for male pheromone amount depending on partner species. Our results demonstrate that the RS-HDL pheromone plays a role in the mating system of N. giraulti and N. oneida, but also that additional communication cues are involved in mate choice. No QTL were found for female mate discrimination which points at a polygenic architecture of female choice with strong environmental influences

Combining data from multiple sources using the CUAHSI Hydrologic Information System (Invited)

The Consortium of Universities for the Advancement of Hydrologic Science, Inc. (CUAHSI) has developed a Hydrologic Information System (HIS) to provide better access to data by enabling the publication, cataloging, discovery, retrieval, and analysis of hydrologic data using web services. The CUAHSI HIS is an Internet based system comprised of hydrologic databases and servers connected through web services as well as software for data publication, discovery and access. The HIS metadata catalog lists close to 100 web services registered to provide data through this system, ranging from large federal agency data sets to experimental watersheds managed by University investigators. The system\u27s flexibility in storing and enabling public access to similarly formatted data and metadata has created a community data resource from governmental and academic data that might otherwise remain private or analyzed only in isolation. Comprehensive understanding of hydrology requires integration of this information from multiple sources. HydroDesktop is the client application developed as part of HIS to support data discovery and access through this system. HydroDesktop is founded on an open source GIS client and has a plug-in architecture that has enabled the integration of modeling and analysis capability with the functionality for data discovery and access. Model integration is possible through a plug-in built on the OpenMI standard and data visualization and analysis is supported by an R plug-in. This presentation will demonstrate HydroDesktop, showing how it provides an analysis environment within which data from multiple sources can be discovered, accessed and integrated

Design of a Metadata Framework for the Environmental Models with an Example Hydrologic Application in HydroShare

Environmental modelers rely on a variety of computational models to make predictions, test hypotheses, and address specific problems related to environmental science and natural resource management. Scientists and engineers must devote significant effort to preparing these computational models. While significant attention has been devoted to sharing and reusing environmental data, less attention has been devoted to sharing and reusing environmental models. A first step toward increasing environmental model sharing and reuse is to define a general metadata framework for models that is flexible and, therefore, applicable across the wide variety of models used by environmental modelers. This paper proposes a general approach for representing environmental model metadata that extends the Dublin Core metadata framework. The framework is implemented within the HydroShare system and applied for a hydrologic model sharing use case. This example application demonstrates how the metadata framework implemented within HydroShare can assist in model sharing, publication, reuse, and reproducibility