Dynamically controlled crystal growth system

Crystal growth can be initiated and controlled by dynamically controlled vapor diffusion or temperature change. In one aspect, the present invention uses a precisely controlled vapor diffusion approach to monitor and control protein crystal growth. The system utilizes a humidity sensor and various interfaces under computer control to effect virtually any evaporation rate from a number of different growth solutions simultaneously by means of an evaporative gas flow. A static laser light scattering sensor can be used to detect aggregation events and trigger a change in the evaporation rate for a growth solution. A control/follower configuration can be used to actively monitor one chamber and accurately control replicate chambers relative to the control chamber. In a second aspect, the invention exploits the varying solubility of proteins versus temperature to control the growth of protein crystals. This system contains miniature thermoelectric devices under microcomputer control that change temperature as needed to grow crystals of a given protein. Complex temperature ramps are possible using this approach. A static laser light scattering probe also can be used in this system as a non-invasive probe for detection of aggregation events. The automated dynamic control system provides systematic and predictable responses with regard to crystal size. These systems can be used for microgravity crystallization projects, for example in a space shuttle, and for crystallization work under terrestial conditions. The present invention is particularly useful for macromolecular crystallization, e.g. for proteins, polypeptides, nucleic acids, viruses and virus particles

Mesoscale simulations of the November 25-26 and December 5-6 cirrus cases using the RAMS model

The Regional Atmospheric Modeling System (RAMS), developed at Colorado State University, was used during the First ISCCP (International Satellite Cloud Climatology Project) Regional Experiment (FIRE) 2 (13 Nov. through 6 Dec. 1991) to provide real time forecasts of cirrus clouds. Forecasts were run once a day, initializing with the 0000 UTC dataset provided by NOAA (Forecast Systems Laboratory (FSL) Mesoscale Analysis and Prediction System (MAPS)). In order to obtain better agreement with observations, a second set of simulations were done for the FIRE 2 cases that occurred on 25-26 Nov. and 5-6 Dec. In this set of simulations, a more complex radiation scheme was used, the Chen/Cotton radiation scheme, along with the nucleation of ice occurring at ice supersaturations as opposed to nucleation occurring at water supersaturations that was done in the actual forecast version. The runs using these more complex schemes took longer wall clock time (7-9 hours for the actual forecasts as compared to 12-14 hrs for the runs using the more complex schemes) however, the final results of the simulations were definitely improved upon. Comparisons between these two sets of simulations are given. Now underway are simulations of these cases using a closed analytical solution for the auto-conversion of ice from a pristine ice class (sizes less than about 50 microns in effective diameter) to a snow class (effective diameters on the order of several hundred microns). This solution is employed along with a new scheme for the nucleation of ice crystals due to Meyers et al and Demott et al. The scheme is derived assuming complete gamma distributions for both the pristine and snow classes. The time rate of change of the number concentration and mass mixing-ratio of each distribution is found by calculating either the flux of crystals that grow beyond a certain critical diameter by vapor deposition in an ice supersaturated regime or by calculating the flux of crystals that evaporate to sizes below that same critical effective diameter

Cellular Models of Aggregation-Dependent Template-Directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer's Disease

Copyright © 2015, The American Society for Biochemistry and Molecular Biology. Acknowledgements-We thank Drs Timo Rager and Rolf Hilfiker (Solvias, Switzerland) for polymorph analyses.Peer reviewedPublisher PD

Adaptative computerized cognitive training decreases mental workload during working memory precision task. A preliminary fNIRS study.

With the growing concern for the health of ageing populations, much research continues to look at the impact of cognitive training, particularly in relation to cognitive decline. We sought to use novel techniques, including augmented reality and portable neurotechnology, to evaluate the impact of a dynamically adjusting cognitive training programme, in comparison to a statically challenging alternative. Before and after an 8-week training period, and at a 5-week follow-up, we used portable functional Near Infrared Spectroscopy to examine mental workload in a mixed battery of cognitive and transfer tasks. A recently developed tablet-based task was used to identify changes in cognitive misbinding. Augmented Reality was used to create a supermarket shopping experience, as a more ecologically valid and realistic transfer task relating to an everyday task relating to independence that quickly becomes difficult with cognitive decline. The analyses showed a decreased mental workload within the dorsolateral prefrontal cortex and that participants considerably increased their performance in the trained task. Some results were maintained at the 5-week follow-up assessment. In terms of transfer, we observed reliable group differences immediately after training completion, which were mainly driven by distinct conditions. Some behavioural memory gains were maintained during the follow-up. The use of novel technologies brought new insights into the effects produced by the dynamic computerised cognitive training programme, which has potential future applications in cognitive decline screening and prevention

ProNGF Induces p75-Mediated Death of Oligodendrocytes following Spinal Cord Injury

AbstractThe neurotrophin receptor p75 is induced by various injuries to the nervous system, but its role after injury has remained unclear. Here, we report that p75 is required for the death of oligodendrocytes following spinal cord injury, and its action is mediated mainly by proNGF. Oligodendrocytes undergoing apoptosis expressed p75, and the absence of p75 resulted in a decrease in the number of apoptotic oligodendrocytes and increased survival of oligodendrocytes. ProNGF is likely responsible for activating p75 in vivo, since the proNGF from the injured spinal cord induced apoptosis among p75+/+, but not among p75−/−, oligodendrocytes in culture, and its action was blocked by proNGF-specific antibody. Together, these data suggest that the role of proNGF is to eliminate damaged cells by activating the apoptotic machinery of p75 after injury

DECOUPLED PAYMENTS IN A CHANGING POLICY SETTING

The studies in this report analyze the effects of decoupled payments in the Federal Agriculture Improvement and Reform (FAIR) Act on recipient households, and assess land, labor, risk management, and capital market conditions that can lead to links between decoupled payments and production choices. Each study contributes a different perspective to understanding the response of U.S. farm households and production to decoupled income transfers. Some use new microdata on farm households collected through USDA's Agricultural Resource Management Survey (ARMS), initiated in 1996, and its predecessor survey. These data are used to compare household and producer behavior and outcomes before and after the FAIR Act. Other studies use applied or conceptual models to characterize the impact of introducing decoupled payments. Collectively, the chapters represent an early stage in the empirical analysis of decoupled payments. The studies address many aspects of the payments' household impacts but remaining issues call for additional analysis. As the analytical paradigm changes with the evolution of farm programs, the development of appropriate data and models will improve our understanding of farm program impacts on the behavior and well-being of U.S. farm households, and the agricultural sector.Agricultural and Food Policy,

Extended thromboprophylaxis with betrixaban in acutely ill medical patients

BACKGROUND: Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. METHODS: Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). CONCLUSIONS: Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218.)

Patient Navigators Connecting Patients to Community Resources to Improve Diabetes Outcomes

BACKGROUND: Despite the recognized importance of lifestyle modification in reducing risk of developing type 2 diabetes and in diabetes management, the use of available community resources by both patients and their primary care providers (PCPs) remains low. The patient navigator model, widely used in cancer care, may have the potential to link PCPs and community resources for reduction of risk and control of type 2 diabetes. In this study we tested the feasibility and acceptability of telephone-based nonprofessional patient navigation to promote linkages between the PCP office and community programs for patients with or at risk for diabetes. METHODS: This was a mixed-methods interventional prospective cohort study conducted between November 2012 and August 2013. We included adult patients with and at risk for type 2 diabetes from six primary care practices. Patient-level measures of glycemic control, diabetes care, and self-efficacy from medical records, and qualitative interview data on acceptability and feasibility, were used. RESULTS: A total of 179 patients participated in the study. Two patient navigators provided services over the phone, using motivational interviewing techniques. Patient navigators provided regular feedback to PCPs and followed up with the patients through phone calls. The patient navigators made 1028 calls, with an average of 6 calls per patient. At follow-up, reduction in HbA1c (7.8 ± 1.9% vs 7.2 ± 1.3%; P = .001) and improvement in patient self-efficacy (3.1 ± 0.8 vs 3.6 ± 0.7; P < .001) were observed. Qualitative analysis revealed uniformly positive feedback from providers and patients. CONCLUSIONS: The patient navigator model is a promising and acceptable strategy to link patient, PCP, and community resources for promoting lifestyle modification in people living with or at risk for type 2 diabetes