American Recovery and Reinvestment Act (ARRA) FEMP Technical Assistance - United States Pacific Command (PACOM) Guam, Task 3.3: Building Retuning Training

Document describes an onsite workshop and building retuning training conducted in Guam in August 2010. Document reports on issues identified during an audit of several buildings and recommendations to save energy throughout the site. During the workshop, it became apparent that as site personnel maintain the facilities at Guam, the following retuning efforts and strategies should be prioritized: (1) Controlling the mechanical systems operational hours and zone temperature set points appeared to present the best opportunities for savings; (2) Zone temperature set points in some buildings are excessively low, especially at night, when the zone temperatures are so cold that they approached the dewpoint; and (3) Manually-set outside air dampers are providing excessive outside air, especially for spaces that are unoccupied. Two of the larger schools, one on the Naval Base and one on Anderson AFB, are in need of a significant recommissioning effort. These facilities are relatively new, with direct digital controls (DDC) but are significantly out of balance. The pressure in one school is extremely negative, which is pulling humid air through the facility each time a door is opened. The draft can be felt several feet down the halls. The pressure in the other school is extremely positive relative to the outside, and you can stand 20-feet outside and still feel cool drafts of air exiting the building. It is recommended that humidity sensors be installed in all new projects and retrofitted into exist facilities. In this humid climate, control of humidity is very important. There are significant periods of time when the mechanical systems in many buildings can be unloaded and dehumidification is not required. The use of CO{sub 2} sensors should also be considered in representative areas. CO{sub 2} sensors determine whether spaces are occupied so that fresh air is only brought into the space when needed. By reducing the amount of outside air brought into the space, the humidity load is also substantially reduced. CO{sub 2} and humidity sensors, combined with outside air sensors, can be used to predict whether conditions are amenable to mold growth and to automatically adjust systems to help prevent mold without using extra energy. The goal of this training is to give the building operators the knowledge needed to make positive changes in the operation of building systems. As class participants apply this knowledge, building systems will run more efficiently, occupant comfort should improve, while saving energy and reducing greenhouse gas emissions

The effect of self-efficacy on behavior and weight in a behavioral weight-loss intervention.

To determine whether eating self-efficacy and physical activity self-efficacy are predictive of dietary intake, physical activity, and weight change within a behavioral weight loss intervention, and whether dietary intake and physical activity mediate relationships between self-efficacy and weight change

Targeted knock-down of miR21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines

We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2

Linking in vitro lipolysis and microsomal metabolism for the quantitative prediction of oral bioavailability of BCS II drugs administered in lipidic formulations

Lipidic formulations (LFs) are increasingly utilized for the delivery of drugs that belong to class II of the Biopharmaceutics Classification System (BCS). The current work proposes, for the first time, the combination of in vitro lipolysis and microsomal metabolism studies for the quantitative prediction of human oral bioavailability of BCS II drugs administered in LFs. Marinol® and Neoral® were selected as model LFs and their observed oral bioavailabilities (Fobserved) obtained from published clinical studies in humans. Two separate lipolysis buffers, differing in the level of surfactant concentrations, were used for digestion of the LFs. The predicted fraction absorbed (Fabs) was calculated by measuring the drug concentration in the micellar phase after completion of the lipolysis process. To determine first-pass metabolism (Fg∙Fh), drug depletion studies with human microsomes were performed. Clearance values were determined by applying the “in vitro half-life approach”. The estimated Fabs and Fg∙Fh values were combined for the calculation of the predicted oral bioavailability (Fpredicted). Results showed that there was a strong correlation between Fobserved and Fpredicted values only when Fabs was calculated using a buffer with surfactant concentrations closer to physiological conditions. The general accuracy of the predicted values suggests that the novel in vitro lipolysis/metabolism approach could quantitatively predict the oral bioavailability of lipophilic drugs administered in LFs

Predicting residue contacts using pragmatic correlated mutations method: reducing the false positives

BACKGROUND: Predicting residues' contacts using primary amino acid sequence alone is an important task that can guide 3D structure modeling and can verify the quality of the predicted 3D structures. The correlated mutations (CM) method serves as the most promising approach and it has been used to predict amino acids pairs that are distant in the primary sequence but form contacts in the native 3D structure of homologous proteins. RESULTS: Here we report a new implementation of the CM method with an added set of selection rules (filters). The parameters of the algorithm were optimized against fifteen high resolution crystal structures with optimization criterion that maximized the confidentiality of the predictions. The optimization resulted in a true positive ratio (TPR) of 0.08 for the CM without filters and a TPR of 0.14 for the CM with filters. The protocol was further benchmarked against 65 high resolution structures that were not included in the optimization test. The benchmarking resulted in a TPR of 0.07 for the CM without filters and to a TPR of 0.09 for the CM with filters. CONCLUSION: Thus, the inclusion of selection rules resulted to an overall improvement of 30%. In addition, the pair-wise comparison of TPR for each protein without and with filters resulted in an average improvement of 1.7. The methodology was implemented into a web server that is freely available to the public. The purpose of this implementation is to provide the 3D structure predictors with a tool that can help with ranking alternative models by satisfying the largest number of predicted contacts, as well as it can provide a confidence score for contacts in cases where structure is known