Use of a Continuous Wave Raman Fiber Laser in Graded-index Multimode Fiber for SRS Beam Combination

We report using a Raman fiber laser (RFL) based on a multimode graded-index fiber as a novel method for beam combination of two continuous wave pump beams. Due to stimulated Raman scattering, the RFL generates a Stokes beam which can be up to 300% brighter than the pump beams. Up to 5.8 W of Stokes power is generated with an optical conversion efficiency of 56%

Certifications Offered by Cost Estimating Organizations

There has been an increasing trend in professional and engineering circles to place greater emphasis on official credentials. These credentials commonly come in the form of certificates – documented recognition by a professional body that an engineer or other professional has the qualifications and technical knowledge to be a practitioner in that field. These certificates are somewhat analogous to merit badges in scouting – the certification is evidence that the holder has a certain minimum level of competence in the subject area. This review will help you decide what certifications are applicable to you and the requirements to obtain a certification

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Cost Estimating Certifications Offered by Professional Societies in the United States and Abroad

Many projects in industry and government go over budget and schedule. In most engineering economics courses, the emphasis is on how to compare alternatives and learn about time value of money and interest and inflation rates. The students are usually given the costs and asked to compare the alternatives. However, this is the easy part of the analysis. The hard part of real project evaluations is developing the cost and investment numbers to do the engineering economics analysis. In most engineering economic textbooks, there is at most one chapter on cost estimation. More and more companies and government organizations are concerned that their engineers don\u27t know how to do accurate cost and schedule estimates. Cost estimation is a critical element to doing engineering economic evaluations. For example, one of the authors has presented short courses on cost estimation and economic evaluation to over 10,000 professionals, mostly engineers and engineering managers who are in industry and government. Most of these engineers have taken engineering economics courses while in college, and they have a good grasp of the fundamentals of engineering economics. However, most practicing engineers lack the fundamentals to do accurate cost and schedule estimates. To keep projects from going over budget and schedule, more and more organizations are requiring their engineers and engineering managers to obtain certifications in cost estimation from professional societies. The purpose of this paper is to discuss the current certifications offered so practicing engineers and engineering educators will know what is available and what is required to earn these certifications. The four major cost estimating certifications offered by professional societies in the United States are discussed. Eligibility and certification requirements along with examination information are presented. In addition, because many engineers are working on international projects, cost estimation certifications offered by professional societies in other countries are also summarized

Ice loss from the East Antarctic Ice Sheet during late Pleistocene interglacials

Understanding ice sheet behaviour in the geological past is essential for evaluating the role of the cryosphere in the climate system and for projecting rates and magnitudes of sea level rise in future warming scenarios1,2,3,4. Although both geological data5,6,7 and ice sheet models3,8 indicate that marine-based sectors of the East Antarctic Ice Sheet were unstable during Pliocene warm intervals, the ice sheet dynamics during late Pleistocene interglacial intervals are highly uncertain3,9,10. Here we provide evidence from marine sedimentological and geochemical records for ice margin retreat or thinning in the vicinity of the Wilkes Subglacial Basin of East Antarctica during warm late Pleistocene interglacial intervals. The most extreme changes in sediment provenance, recording changes in the locus of glacial erosion, occurred during marine isotope stages 5, 9, and 11, when Antarctic air temperatures11 were at least two degrees Celsius warmer than pre-industrial temperatures for 2,500 years or more. Hence, our study indicates a close link between extended Antarctic warmth and ice loss from the Wilkes Subglacial Basin, providing ice-proximal data to support a contribution to sea level from a reduced East Antarctic Ice Sheet during warm interglacial intervals. While the behaviour of other regions of the East Antarctic Ice Sheet remains to be assessed, it appears that modest future warming may be sufficient to cause ice loss from the Wilkes Subglacial Basin

Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles

<div><p>Recent development of benzoxaborole-based chemistry gave rise to a collection of compounds with great potential in targeting diverse infectious diseases, including human African Trypanosomiasis (HAT), a devastating neglected tropical disease. However, further medicinal development is largely restricted by a lack of insight into mechanism of action (MoA) in pathogenic kinetoplastids. We adopted a multidisciplinary approach, combining a high-throughput forward genetic screen with functional group focused chemical biological, structural biology and biochemical analyses, to tackle the complex MoAs of benzoxaboroles in <i>Trypanosoma brucei</i>. We describe an oxidative enzymatic pathway composed of host semicarbazide-sensitive amine oxidase and a trypanosomal aldehyde dehydrogenase TbALDH3. Two sequential reactions through this pathway serve as the key underlying mechanism for activating a series of 4-aminomethylphenoxy-benzoxaboroles as potent trypanocides; the methylamine parental compounds as pro-drugs are transformed first into intermediate aldehyde metabolites, and further into the carboxylate metabolites as effective forms. Moreover, comparative biochemical and crystallographic analyses elucidated the catalytic specificity of TbALDH3 towards the benzaldehyde benzoxaborole metabolites as xenogeneic substrates. Overall, this work proposes a novel drug activation mechanism dependent on both host and parasite metabolism of primary amine containing molecules, which contributes a new perspective to our understanding of the benzoxaborole MoA, and could be further exploited to improve the therapeutic index of antimicrobial compounds.</p></div

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

Low-N protein engineering with data-efficient deep learning

Protein engineering has enormous academic and industrial potential. However, it is limited by the lack of experimental assays that are consistent with the design goal and sufficiently high throughput to find rare, enhanced variants. Here we introduce a machine learning-guided paradigm that can use as few as 24 functionally assayed mutant sequences to build an accurate virtual fitness landscape and screen ten million sequences via in silico directed evolution. As demonstrated in two dissimilar proteins, GFP from Aequorea victoria (avGFP) and E. coli strain TEM-1 β-lactamase, top candidates from a single round are diverse and as active as engineered mutants obtained from previous high-throughput efforts. By distilling information from natural protein sequence landscapes, our model learns a latent representation of 'unnaturalness', which helps to guide search away from nonfunctional sequence neighborhoods. Subsequent low-N supervision then identifies improvements to the activity of interest. In sum, our approach enables efficient use of resource-intensive high-fidelity assays without sacrificing throughput, and helps to accelerate engineered proteins into the fermenter, field and clinic

Project and Engineering Management Certificates Offered by Professional Organizations

This paper summarizes five major project management (PM) certificates and two major engineering management (EM) certificates offered in the United States by professional organizations. The two EM certificates are offered by Engineering Management Certification International, an organization developed in cooperation with the American Society of Civil Engineers. Information is given on the number of people holding the certification, eligibility to get the certification, exam format, cost for the certification, and contact information for the organization offering the certification. The information is summarized and organized into four tables: general information, eligibility and certification requirements, exam information, and U.S.-based organizations’ contact information. This paper also includes information for organizations outside the United States offering PM certification in thirty-three countries. Finally, a new international PM certification offered by a U.S.-based organization is discussed. This paper will help you decide what certifications are applicable to you and the requirements to obtain a certification