Distribution of anthropogenic mercury in a forested wetland.

Undergraduate Research Exper.As global usage of mercury and methylmercury increases, climate change will impact its distribution and movement in unexpected ways. In wetlands, elemental mercury (Hg) is methylated into its more environmentally toxic form, methylmercury ([CH3Hg+]). The two main sources for anthropogenic mercury are atmospheric deposition and legacy soil mercury. Methylmercury bio-accumulates and causes neurological damage to terrestrial and aquatic organisms. Our research demonstrated that there was mercury within the forested wetland watershed. Also, the analysis suggested that although organic carbon was an indicator for the presence of Hg. However, the best predictor was when horizon mid-point, % C, and δ13C parameters were all considered together. Studying the dynamics and distribution of mercury within wetlands can inform environmental and resource managers on best practices to mitigate these ecological health issues.http://deepblue.lib.umich.edu/bitstream/2027.42/116615/1/Thompson_Carl_REU_2015.pd

Long-term Browsing Impacts on Montana Ungulate Ranges

Ungulate impacts on woody vegetation have been a concern on Montana wildlife habitats for more than a half-century. Fenced areas restricting access of all ungulates (exclosures) were established between 1944 and 1988 on many habitats to evaluate ungulate impacts on shrubs. Our objective was to determine the effect of long-term browsing on big sagebrush (Artemisia tridentata), bitterbrush (Purshia tridentata), curlleaf mountain mahogany (Cercocarpus ledifolius) and horizontal juniper (Juniperus horizontalis). We hypothesized that the long-term effect of ungulate browsing would not impact these common shrubs. Canopy cover and density of shrubs were measured in and out of exclosures (n =14) on environmentally paired sites. Big sagebrush canopy cover, density of mature big sagebrush, and production of winter forage (n =7) were greater with protection on four sites (P ≤ 0.05). Differences were not restricted to one subspecies of big sagebrush. Bitterbrush canopy cover and density of mature shrubs (n =3) were greater with protection on two sites (P ≤ 0.05). Curlleaf mountain mahogany canopy cover (n =2) was greater with protection on both sites (P ≤ 0.05), while density of mature mahogany was greater at one site (P ≤ 0.05). Horizontal juniper cover (n =2) was greater with protection at both sites (P ≤ 0.01). We rejected our hypothesis at ten of the 14 sites evaluated. Long-term ungulate browsing has impacted shrubs at ten sites that are not geographically related. This has implications to plant communities and value of shrub habitats to wildlife

A systematic review of biomarkers for disease progression in Parkinson's disease

This article presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0707-10124).BACKGROUND: Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential neuroprotective agents from true disease-modifying effects. A systematic review was undertaken to determine what biomarkers for disease progression in Parkinson's disease (PD) exist. METHODS: MEDLINE and EMBASE (1950-2010) were searched using five search strategies. Abstracts were assessed to identify papers meriting review in full. Studies of participants with idiopathic PD diagnosed by formal criteria or clearly described clinical means were included. We made no restriction on age, disease duration, drug treatment, or study design. We included studies which attempted to draw associations between any tests used to investigate disease progression and any clinical measures of disease progression. The electronic search was validated by hand-searching the two journals from which most included articles came. RESULTS: 183 studies were included: 163 (89%) cross-sectional, 20 (11%) longitudinal. The electronic search strategy had a sensitivity of 71.4% (95% CI 51.1-86.0) and a specificity of 97.1% (95% CI 96.5-97.7). In longitudinal studies median follow-up was 2.0 years (IQR 1.1-3.5). Included studies were generally poor quality--cross-sectional with small numbers of participants, applying excessive inclusion/exclusion criteria, with flawed methodologies and simplistic statistical analyses. CONCLUSION: We found insufficient evidence to recommend the use of any biomarker for disease progression in PD clinical trials, which may simply reflect the poor quality of research in this area. We therefore present a provisional 'roadmap' for conducting future disease progression biomarker studies, and recommend new quality criteria by which future studies may be judged.Publisher PDFPeer reviewe

GNOMES II: Analysis of the Galactic diffuse molecular ISM in all four ground state hydroxyl transitions using Amoeba

We present observations of the four 2 Pi 3/2 J = 3/2 ground-rotational state transitions of the hydroxyl molecule (OH) along 107 lines of sight both in and out of the Galactic plane: 92 sets of observations from the Arecibo telescope and 15 sets of observations from the Australia Telescope Compact Array (ATCA). Our Arecibo observations included off-source pointings, allowing us to measure excitation temperature (Tex) and optical depth, while our ATCA observations give optical depth only. We perform Gaussian decomposition using the Automated Molecular Excitation Bayesian line-fitting Algorithm 'AMOEBA' (Petzler, Dawson, and Wardle 2021) fitting all four transitions simultaneously with shared centroid velocity and width. We identify 109 features across 38 sightlines (including 58 detections along 27 sightlines with excitation temperature measurements). While the main lines at 1665 and 1667 MHz tend to have similar excitation temperatures (median Tex(main) difference = 0.6 K, 84% show Tex(main) difference < 2 K), large differences in the 1612 and 1720 MHz satellite line excitation temperatures show that the gas is generally not in LTE. For a selection of sightlines we compare our OH features to associated (on-sky and in velocity) HI cold gas components (CNM) identified by Nguyen et al. (2019) and find no strong correlations. We speculate that this may indicate an effective decoupling of the molecular gas from the CNM once it accumulates.Comment: Accepted for publication to PASA. 41 pages, 27 figure

Synergistic drug combinations from electronic health records and gene expression.

ObjectiveUsing electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding.MethodWe applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. We identified differentially expressed genes from 14 case-control human breast cancer gene expression datasets and integrated them with drug-protein networks. Drugs in the network were scored according to their association with breast cancer individually or in pairs. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis.ResultsFrom EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. The first 2 pairs were also enriched among pairs discovered using gene expression data and are supported by molecular interactions in drug-protein networks and preclinical and epidemiologic evidence.ConclusionsThis is a proof-of-concept study demonstrating that a combination of complementary data sources, such as EHRs and gene expression, can corroborate discoveries and provide mechanistic insight into drug synergism for repurposing

Focused Ion Beam Fabrication

Contains reports on five research projects.DARPA/Naval Electronic Systems Command (Contract MDA-903-85-C-0215)Charles Stark Draper Laboratory (Contract DL-H-261827)U.S. Navy - Office of Naval Research (Contract N00014-84-K-0073)Nippon Telephone and TelegraphHitachi Central Research Laborator

Bulk and Interfacial Shear Thinning of Immiscible Polymers

Nonequilibrium molecular dynamics simulations are used to study the shear thinning behavior of immiscible symmetric polymer blends. The phase separated polymers are subjected to a simple shear flow imposed by moving a wall parallel to the fluid-fluid interface. The viscosity begins to shear thin at much lower rates in the bulk than at the interface. The entire shear rate dependence of the interfacial viscosity is consistent with a shorter effective chain length $s^*$ that also describes the width of the interface. This $s^*$ is independent of chain length $N$ and is a function only of the degree of immiscibility of the two polymers. Changes in polymer conformation are studied as a function of position and shear rate.Shear thinning correlates more closely with a decrease in the component of the radius of gyration along the velocity gradient than with elongation along the flow. At the interface, this contraction of chains is independent of $N$ and consistent with the bulk behavior for chains of length $s^*$. The distribution of conformational changes along chains is also studied. Central regions begin to stretch at a shear rate that decreases with increasing $N$, while shear induced changes at the ends of chains are independent of $N$.Comment: 8 pages, 8 figure

Cost and feasibility: an exploratory case study comparing use of a literature review method with questionnaires, interviews and focus groups to identify barriers for a behaviour-change intervention

Background: It is often recommended that behaviour-change interventions be tailored to barriers. There is a scarcity of research into the best method of barrier identification, although combining methods has been suggested to be beneficial. This paper compares the feasibility and costs of three different methods of barrier identification used in three implementation projects conducted in primary care. Methods: Underpinned by a theory-base, project one used a questionnaire and interviews; project two used a single focus group and questionnaire, and project three used a literature review of published barriers. The feasibility of each project, as experienced by the research team, and labour costs are summarised. Results: The literature review of published barriers was the least costly and most feasible method, being quick to conduct and avoiding the challenges of recruitment experienced when using interviews or a questionnaire. The feasibility of using questionnaires was further reduced by the time taken develop the instruments. Conducting a single focus group was also found to be a more feasible method, taking less time than interviews to collect and analyse the barriers. Conclusions: Considering the ease of recruitment, time required and cost of the different methods to collect barriers is crucial at the start of implementation studies. The literature review method is the least costly and most feasible method. Use of a single focus group was found to be more feasible than conducting individual interviews or administering a questionnaire, with less recruitment challenges experienced, and quicker data collection. Future research would benefit from comparing the robustness of the methods in terms of the comprehensiveness of barriers identified

Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers

<p>Abstract</p> <p>Background</p> <p>Amyloid-related degenerative diseases are associated with the accumulation of misfolded proteins as amyloid fibrils in tissue. In Alzheimer disease (AD), amyloid accumulates in several distinct types of insoluble plaque deposits, intracellular Aβ and as soluble oligomers and the relationships between these deposits and their pathological significance remains unclear. Conformation dependent antibodies have been reported that specifically recognize distinct assembly states of amyloids, including prefibrillar oligomers and fibrils.</p> <p>Results</p> <p>We immunized rabbits with a morphologically homogeneous population of Aβ42 fibrils. The resulting immune serum (OC) specifically recognizes fibrils, but not random coil monomer or prefibrillar oligomers, indicating fibrils display a distinct conformation dependent epitope that is absent in prefibrillar oligomers. The fibril epitope is also displayed by fibrils of other types of amyloids, indicating that the epitope is a generic feature of the polypeptide backbone. The fibril specific antibody also recognizes 100,000 × G soluble fibrillar oligomers ranging in size from dimer to greater than 250 kDa on western blots. The fibrillar oligomers recognized by OC are immunologically distinct from prefibrillar oligomers recognized by A11, even though their sizes overlap broadly, indicating that size is not a reliable indicator of oligomer conformation. The immune response to prefibrillar oligomers and fibrils is not sequence specific and antisera of the same specificity are produced in response to immunization with islet amyloid polypeptide prefibrillar oligomer mimics and fibrils. The fibril specific antibodies stain all types of amyloid deposits in human AD brain. Diffuse amyloid deposits stain intensely with anti-fibril antibody although they are thioflavin S negative, suggesting that they are indeed fibrillar in conformation. OC also stains islet amyloid deposits in transgenic mouse models of type II diabetes, demonstrating its generic specificity for amyloid fibrils.</p> <p>Conclusion</p> <p>Since the fibril specific antibodies are conformation dependent, sequence-independent, and recognize epitopes that are distinct from those present in prefibrillar oligomers, they may have broad utility for detecting and characterizing the accumulation of amyloid fibrils and fibrillar type oligomers in degenerative diseases.</p