Improving Steam System Operation and Management

This paper documents the design and construction of a world-class steam system institute. Steam systems provide heat and energy for high performance buildings. However, incoming technicians have little to no technical education for steam systems and no steam institutes exist today. While new technicians are introduced to steam systems for 20 hours of in class sessions, there are little opportunities for hands on experience. Furthermore, steam systems, if not maintained properly, are dangerous and new personnel need hands on experience to ensure safety and adherence to standard protocol. A new world-class steam system institute will provide incoming technicians with knowledge of proper steam distribution, condensation, and return. The system will contain a smaller scale of all necessary components seen in the field. Not only examples of equipment, but also common mistakes made in typical steam systems, such as poorly pitched pipe, will be demonstrated. The design of the steam system includes common valves, heat exchangers, steam traps, flash tanks, regulators, automation, and more. With the knowledge of steam system components and common mistakes, new technicians will be able to provide more satisfactory operations and management reducing maintenance costs. Understanding processes, and incorrect practices, before entering the field, will improve the safety and smoothness of steam system operations in facilities. The state-of-the-art steam system institute will prepare students with a comprehensive understanding of a scaled-down steam system and confidence in the field

Understanding Uncertainties in Model-Based Predictions of Aedes aegypti Population Dynamics

Dengue is one of the most important insect-vectored human viral diseases. The principal vector is Aedes aegypti, a mosquito that lives in close association with humans. Currently, there is no effective vaccine available and the only means for limiting dengue outbreaks is vector control. To help design vector control strategies, spatial models of Ae. aegypti population dynamics have been developed. However, the usefulness of such models depends on the reliability of their predictions, which can be affected by different sources of uncertainty including uncertainty in the model parameter estimation, uncertainty in the model structure, measurement errors in the data fed into the model, individual variability, and stochasticity in the environment. This study quantifies uncertainties in the mosquito population dynamics predicted by Skeeter Buster, a spatial model of Ae. aegypti, for the city of Iquitos, Peru. The uncertainty quantification should enable us to better understand the reliability of model predictions, improve Skeeter Buster and other similar models by targeting those parameters with high uncertainty contributions for further empirical research, and thereby decrease uncertainty in model predictions

Skeeter Buster: A Stochastic, Spatially Explicit Modeling Tool for Studying Aedes aegypti Population Replacement and Population Suppression Strategies

Dengue is a viral disease that affects approximately 50 million people annually, and is estimated to result in 12,500 fatalities. Dengue viruses are vectored by mosquitoes, predominantly by the species Aedes aegypti. Because there is currently no vaccine or specific treatment, the only available strategy to reduce dengue transmission is to control the populations of these mosquitoes. This can be achieved by traditional approaches such as insecticides, or by recently developed genetic methods that propose the release of mosquitoes genetically engineered to be unable to transmit dengue viruses. The expected outcome of different control strategies can be compared by simulating the population dynamics and genetics of mosquitoes at a given location. Development of optimal control strategies can then be guided by the modeling approach. To that end, we introduce a new modeling tool called Skeeter Buster. This model describes the dynamics and the genetics of Ae. aegypti populations at a very fine scale, simulating the contents of individual houses, and even the individual water-holding containers in which mosquito larvae reside. Skeeter Buster can be used to compare the predicted outcomes of multiple control strategies, traditional or genetic, making it an important tool in the fight against dengue

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children