Isotopic heterogeneity in U.S. Urban water supply systems reflects climatic, environmental, and sociodemographic factors: Implications for forensic identification.

The forensic application of stable oxygen isotope data from human tissues depends on naturally occurring isotopic variation in drinking water across geographic areas. One factor which complicates interpretation of forensic data is local variability: if a wide range of drinking water values is in a small geographic region it may be difficult to identify or rule out that region as a location of origin. We examine data from community collection programs documenting tap water isotope variation within 30 cities\developed areas throughout the United States.

Urbanization and Suspended Sediment Transport Dynamics: A Comparative Study of Watersheds with Varying Degree of Urbanization Using Concentration-Discharge Hysteresis.

Suspended sediment is a critical water quality parameter and an indicator of geomorphic processes, but suspended sediment dynamics in urban streams may not conform to the first-flush model widely used for other pollutants. We analyzed discharge and turbidity data for 367 events from three urban watersheds (impervious cover 16-45%) in Cleveland, Ohio (USA). Less intensely urbanized watersheds exhibit higher turbidity compared to that of the most highly urbanized watershed.

Human amyotrophic lateral sclerosis excitability phenotype screen: Target discovery and validation.

Drug development is hampered by poor target selection. Phenotypic screens using neurons differentiated from patient stem cells offer the possibility to validate known and discover novel disease targets in an unbiased fashion. To identify targets for managing hyperexcitability, a pathological feature of amyotrophic lateral sclerosis (ALS), we design a multi-step screening funnel using patient-derived motor neurons.

Bioretention cell age and construction style influence stormwater pollutant dynamics.

In urbanized landscapes, green infrastructure is proposed as a method for using relatively small plots of land to manage stormwater and protect receiving ecosystems from pollutants. Bioretention cells can infiltrate stormwater from roads and parking lots, and as stormwater passed through the soils, metals can be removed. Metal removal and storage has been demonstrated in laboratory media columns and field-scale test cells, but we have an incomplete understanding of metal removal and accumulation in aging bioretention cells in the field.

A global view on the effect of water uptake on aerosol particle light scattering.

A reference dataset of multi-wavelength particle light scattering and hemispheric backscattering coefficients for different relative humidities (RH) between RH = 30 and 95% and wavelengths between λ = 450 nm and 700 nm is described in this work. Tandem-humidified nephelometer measurements from 26 ground-based sites around the globe, covering multiple aerosol types, have been re-analysed and harmonized into a single dataset. The dataset includes multi-annual measurements from long-term monitoring sites as well as short-term field campaign data.

Design and synthesis of potent RSK inhibitors.

Utilizing the already described 3,4-bi-aryl pyridine series as a starting point, incorporation of a second ring system with a hydrogen bond donor and additional hydrophobic contacts yielded the azaindole series which exhibited potent, picomolar RSK2 inhibition and the most potent in vitro target modulation seen thus far for a RSK inhibitor. In the context of the more potent core, several changes at the phenol moiety were assessed to potentially find a tool molecule appropriate for in vivo evaluation.

Corrigendum: Collocated observations of cloud condensation nuclei, particle size distributions, and chemical composition.

This corrects the article DOI: 10.1038/sdata.2017.

Prevalence and Characterization of and Methicillin-Resistant on Public Recreational Beaches in Northeast Ohio.

can cause severe life-threatening illnesses such as sepsis and endocarditis. Although has been isolated from marine water and intertidal beach sand, only a few studies have been conducted to assess prevalence of at freshwater recreational beaches. As such, we aimed to determine prevalence and molecular characteristics of in water and sand at 10 freshwater recreational beaches in Northeast Ohio, USA.

Collocated observations of cloud condensation nuclei, particle size distributions, and chemical composition.

Cloud condensation nuclei (CCN) number concentrations alongside with submicrometer particle number size distributions and particle chemical composition have been measured at atmospheric observatories of the Aerosols, Clouds, and Trace gases Research InfraStructure (ACTRIS) as well as other international sites over multiple years. Here, harmonized data records from 11 observatories are summarized, spanning 98,677 instrument hours for CCN data, 157,880 for particle number size distributions, and 70,817 for chemical composition data. The observatories represent nine different environments, e.

Azaindoles as Zinc-Binding Small-Molecule Inhibitors of the JAMM Protease CSN5.

CSN5 is the zinc metalloprotease subunit of the COP9 signalosome (CSN), which is an important regulator of cullin-RING E3 ubiquitin ligases (CRLs). CSN5 is responsible for the cleavage of NEDD8 from CRLs, and blocking deconjugation of NEDD8 traps the CRLs in a hyperactive state, thereby leading to auto-ubiquitination and ultimately degradation of the substrate recognition subunits. Herein, we describe the discovery of azaindoles as a new class of CSN5 inhibitors, which interact with the active-site zinc ion of CSN5 through an unprecedented binding mode.

Characterizing the Effects of Stormwater Mitigation on Nutrient Export and Stream Concentrations.

Urbanization increases nutrient loading and lowers residence times for processing of reactive solutes, including nitrate, total dissolved nitrogen, orthophosphate, and dissolved organic carbon), which leads to increased stream concentrations and mass export. Stormwater control measures mitigate the impacts of urbanization, and have the potential to improve stream water quality, however the net effect instream is not well understood. We monitored two urban and two suburban watersheds in Charlotte, NC to determine if mitigation controlled the fraction of total mass export during storm, if development classification as either urban or suburban (defined by the age, density and distribution of urban development) controlled storm nutrient and carbon dynamics, and if stormwater control measures were able to change stream water chemistry.

Targeted inhibition of the COP9 signalosome for treatment of cancer.

The COP9 signalosome (CSN) is a central component of the activation and remodelling cycle of cullin-RING E3 ubiquitin ligases (CRLs), the largest enzyme family of the ubiquitin-proteasome system in humans. CRLs are implicated in the regulation of numerous cellular processes, including cell cycle progression and apoptosis, and aberrant CRL activity is frequently associated with cancer. Remodelling of CRLs is initiated by CSN-catalysed cleavage of the ubiquitin-like activator NEDD8 from CRLs.

Satellite retrieval of cloud condensation nuclei concentrations by using clouds as CCN chambers.

Quantifying the aerosol/cloud-mediated radiative effect at a global scale requires simultaneous satellite retrievals of cloud condensation nuclei (CCN) concentrations and cloud base updraft velocities (Wb). Hitherto, the inability to do so has been a major cause of high uncertainty regarding anthropogenic aerosol/cloud-mediated radiative forcing. This can be addressed by the emerging capability of estimating CCN and Wb of boundary layer convective clouds from an operational polar orbiting weather satellite.

Discovery of Potent and Selective RSK Inhibitors as Biological Probes.

While the p90 ribosomal S6 kinase (RSK) family has been implicated in multiple tumor cell functions, the full understanding of this kinase family has been restricted by the lack of highly selective inhibitors. A bis-phenol pyrazole was identified from high-throughput screening as an inhibitor of the N-terminal kinase of RSK2. Structure-based drug design using crystallography, conformational analysis, and scaffold morphing resulted in highly optimized difluorophenol pyridine inhibitors of the RSK kinase family as demonstrated cellularly by the inhibition of YB1 phosphorylation.

Novel potent and selective inhibitors of p90 ribosomal S6 kinase reveal the heterogeneity of RSK function in MAPK-driven cancers.

Unlabelled: The p90 ribosomal S6 kinase (RSK) family of serine/threonine kinases is expressed in a variety of cancers and its substrate phosphorylation has been implicated in direct regulation of cell survival, proliferation, and cell polarity. This study characterizes and presents the most selective and potent RSK inhibitors known to date, LJH685 and LJI308. Structural analysis confirms binding of LJH685 to the RSK2 N-terminal kinase ATP-binding site and reveals that the inhibitor adopts an unusual nonplanar conformation that explains its excellent selectivity for RSK family kinases.

2-Amino-7-substituted benzoxazole analogs as potent RSK2 inhibitors.

2-Amino-7-substituted benzoxazole analogs were identified by HTS as inhibitors of RSK2. Molecular modeling and medicinal chemistry techniques were employed to explore the SAR for this series with a focus of improving in vitro and target modulation potency and physicochemical properties.

The capillary index score: rethinking the acute ischemic stroke treatment algorithm. Results from the Borgess Medical Center Acute Ischemic Stroke Registry.

Background: Despite increased recanalization rates in the treatment of acute ischemic stroke, the percentage of patients with a good clinical outcome of all those treated has not risen above 50%. This 50% barrier may be broken by improving the criteria for treatment selection. This study investigated the addition of the capillary index score (CIS), a new index for assessing remaining viable tissue in the ischemic area, to the existing criteria.

Vertebral artery ostium atherosclerotic plaque as a potential source of posterior circulation ischemic stroke: result from borgess medical center vertebral artery ostium stenting registry.

Background And Purpose: Although atherosclerotic plaque in the carotid and coronary arteries is accepted as a cause of ischemia, vertebral artery ostium (VAO) atherosclerotic plaque is not widely recognized as a source of ischemic stroke. We seek to demonstrate its implication in some posterior circulation ischemia.

Methods: This is a nonrandomized, prospective, single-center registry on consecutive patients presenting with posterior circulation ischemia who underwent VAO stenting for significant atherosclerotic stenosis.

Factors associated with recruitment and retention of youth into smoking cessation intervention studies--a review of the literature.

This paper examines factors associated with high levels of recruitment and retention of youth into smoking cessation interventions. Fifty-five articles published from 1976 to June 2004 reported cessation outcomes were analyzed to examine the associations between selected variables and recruitment and retention rates. Studies with participants who smoked < or =5 cigarettes per day (cpd) were more likely to have recruitment rates > or =85%.