High-throughput analysis of native antibody repertoires for therapeutics discovery

Adaptive immunity is the foundation of recognition and protection against a diverse array of pathogens. The humoral arm of adaptive immunity whose most significant effector mechanism relies on antibodies is critical for protection against many viral and bacterial pathogens. Additionally, antibodies are extremely important for clinical medicine either as therapeutics or for detection purposes. As a result, there is great interest in the development of technologies for isolating therapeutically or diagnostically useful antibodies from immunized animals or from patients. In this work I describe several high throughput approaches for the “mining” of the mammalian adaptive antibody response for the purpose of isolating antibodies with high affinity and selectivity towards desired antigens. The first technology capitalizes on the fact that the antibody repertoire encoded by B cells in the draining lymph node from the immunization site is highly enriched for antibodies specific to the immunogen. The second technology takes advantage of repertoire analysis by next-generation sequencing and yeast display for antibody discovery. The third technology integrates high-throughput V [subscript H] :V [subscript L] pairing with yeast surface display to enable rapid, high-throughput screening of all native antibodies in the repertoire. These three technologies have been used to identify a large panel of antibodies against several different pathogens, including Ebola virus, ricin, influenza virus, and HIV-1 virus. These technologies will continue to play a critical role in adaptive immunity exploration for new therapeutics discovery, and in characterization of immune responses elicited by vaccination or natural infection to guide design of more effective vaccines.Chemical Engineerin

Shape-selective catalysts for Fischer-Tropsch chemistry : iron-containing particulate catalysts. Activity report : January 1, 2001 - December 31, 2004.

Argonne National Laboratory is carrying out a research program to create, prepare, and evaluate catalysts to promote Fischer-Tropsch (FT) chemistry--specifically, the reaction of hydrogen with carbon monoxide to form long-chain hydrocarbons. In addition to needing high activity, it is desirable that the catalysts have high selectivity and stability with respect to both mechanical strength and aging properties. It is desired that selectivity be directed toward producing diesel fraction components and avoiding excess yields of both light hydrocarbons and heavy waxes. The goal is to produce shape-selective catalysts that have the potential to limit the formation of longchain products and yet retain the active metal sites in a protected 'cage'. This cage also restricts their loss by attrition during use in slurry-bed reactors. The first stage of this program was to prepare and evaluate iron-containing particulate catalysts. This activity report centers upon this first stage of experimentation with particulate FT catalysts. (For reference, a second experimental stage is under way to prepare and evaluate active FT catalysts formed by atomic-layer deposition [ALD] of active components on supported membranes.) To date, experimentation has centered upon the evaluation of a sample of iron-based, spray-dried catalyst prepared by B.H. Davis of the Center of Applied Energy Research (CAER) and samples of his catalyst onto which inorganic 'shells' were deposited. The reference CAER catalyst contained a high level of dispersed fine particles, a portion of which was removed by differential settling. Reaction conditions have been established using a FT laboratory unit such that reasonable levels of CO conversion can be achieved, where therefore a valid catalyst comparison can be made. A wide range of catalytic activities was observed with SiO{sub 2}-coated FT catalysts. Two techniques were used for SiO{sub 2}coating. The first involved a caustic precipitation of SiO{sub 2} from an organo-silicate onto the CAER catalyst. The second was the acidic precipitation of an organo-silicate with aging to form fractal particles that were then deposited onto the CAER catalyst. Several resulting FT catalysts were as active as the coarse catalyst on which they were prepared. The most active ones were those with the least amount of coating, namely about 2.2 wt% SiO{sub 2}. In the case of the latter acid technique, the use of HCl and HNO{sub 3} was much more effective than that of H{sub 2}SO{sub 4}. Scanning electron microscopy (SEM) was used to observe and analyze as-received and treated FT catalysts. It was observed that (1) spherical particles of CAER FT catalyst were made up of agglomerates of particles that were, in turn, also agglomerates; (2) the spray drying process of CAER apparently concentrated the Si precursor at the surface during drying; (3) while SEM pointed out broad differences in the appearance of the prepared catalyst particles, there was little indication that the catalysts were being uniformly coated with a cage-like protective surface, with perhaps the exception of HNO{sub 3}-precipitated catalyst; and (4) there was only a limited penetration of carbon (i.e., CO) into the FT catalyst during the conditioning and FT reaction steps

Teaching Chemistry to Students with Disabilities: A Manual For High Schools, Colleges, and Graduate Programs - Edition 4.1

Ever since it was first published, Teaching Chemistry to Students with Disabilities: A Manual for High Schools, Colleges, and Graduate Programs has served as a vital resource in the chemistry classroom and laboratory to students with disabilities as well as their parents, teachers, guidance counselors, and administrators. The comprehensive 4th edition was last updated in 2001, so the American Chemical Society’s (ACS) Committee on Chemists with Disabilities (CWD) thought it prudent to update such a valuable text at this time. In a changing time of technology, rapid access to information, accessibility tools for individuals with disabilities, and publishing, Edition 4.1 is being published digitally/online as an Open Access text. Having Teaching Chemistry to Students with Disabilities: A Manual for High Schools, Colleges, and Graduate Programs in this format will allow for widespread dissemination and access by maximum numbers of readers at no cost- and will allow the text to remain economically sustainable.https://scholarworks.rit.edu/ritbooks/1001/thumbnail.jp

Sustainable risk management of emerging contaminants in municipal wastewaters

This article is available open access through the publisher’s website at the link below. Copyright @ 2009 The Royal Society.The presence of emerging contaminants in municipal wastewaters, particularly endocrine-disrupting compounds such as oestrogenic substances, has been the focus of much public concern and scientific attention in recent years. Due to the scientific uncertainty still surrounding their effects, the Precautionary Principle could be invoked for the interim management of potential risks. Therefore, precautionary prevention risk-management measures could be employed to reduce human exposure to the compounds of concern. Steroid oestrogens are generally recognized as the most significant oestrogenically active substances in domestic sewage effluent. As a result, the UK Environment Agency has championed a ‘Demonstration Programme’ to investigate the potential for removal of steroid oestrogens and alkylphenol ethoxylates during sewage treatment. Ecological and human health risks are interdependent, and ecological injuries may result in increased human exposures to contaminants or other stressors. In this context of limiting exposure to potential contaminants, examining the relative contribution of various compounds and pathways should be taken into account when identifying effective risk-management measures. In addition, the explicit use of ecological objectives within the scope of the implementation of the EU Water Framework Directive poses new challenges and necessitates the development of ecosystem-based decision tools. This paper addresses some of these issues and proposes a species sensitivity distribution approach to support the decision-making process related to the need and implications of sewage treatment work upgrade as risk-management measures to the presence of oestrogenic compounds in sewage effluent

Optimal design and operation of energy polygeneration systems

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (p. 301-319).Polygeneration is a concept where multiple energy products are generated in a single plant by tightly integrating multiple processes into one system. Compared to conventional single-product systems, polygeneration systems have many economic advantages, such as potentially high profitability and high viability when exposed to market fluctuations. The optimal design of an energy polygeneration system that converts coal and biomass to electricity, liquid fuels (naphtha and diesel) and chemical products (methanol) with carbon dioxide (CO²) capture under different economic scenarios is investigated. In this system, syngas is produced by gasification of coal and/or biomass; purified by a cleaning process to remove particles, mercury, sulfur and CO²; and then split to different downstream sections such as the gas turbine, FT process and the methanol process. In this thesis, the optimal design with the highest net present value (NPV) is determined by optimizing equipment capacities, stream flow rates and stream split fractions. The case study results for static polygeneration systems reveal that the optimal design of polygeneration systems is strongly influenced by economic conditions such as feedstock prices, product prices, and potential emissions penalties for CO². Over the range of economic scenarios considered, it can be optimal to produce a mixture of electricity, liquid fuels, and methanol; only one each; or mixtures in-between. The optimal biomass/coal feed ratio significantly increases when the carbon tax increases or the biomass price decreases. An economic analysis of the optimal static polygeneration designs yielded a slightly higher NPV than comparable single-product plants. The flexible operation is then considered for the energy polygeneration system. In real applications, product prices can fluctuate significantly seasonally or even daily. The profitability of the polygeneration system can potentially be increased if some operational flexibility is introduced, such as adjusting the product mix in response to changing market prices. The major challenge of this flexible design is the determination of the optimal trade-off between flexibility and capital cost because higher flexibility typically implies both higher product revenues and larger equipment sizes. A two-stage optimization formulation for is used for the optimal design and operation of flexible energy polygeneration systems, which simultaneously optimizes design decision variables (e.g., equipment sizes) and operational decision variables (e.g., production rate schedules) in several different market scenarios to achieve the best expected economic performance. Case study results for flexible polygeneration systems show that for most of market scenarios, flexible polygeneration systems achieved higher expected NPVs than static polygeneration systems. Furthermore, even higher expected NPVs could be obtained with increases in flexibility. The flexible polygeneration optimization problem is a potentially large-scale nonconvex mixed-integer nonlinear program (MINLP) and cannot be solved to global optimality by state-of-the-art global optimization solvers, such as BARON, within a reasonable time. The nonconvex generalized Benders decomposition (NGBD) method can exploit the special structure of this mathematical programming problem and enable faster solution. In this method, the nonconvex MINLP is relaxed into a convex lower bounding problem which can be further reformulated into a relaxed master problem according to the principles of projection, dualization and relaxation. The relaxed master problem yields an nondecreasing sequence of lower bounds for the original problem. And an nonincreasing sequence of upper bounds is obtained by solving primal problems, which are generated by fixing the integer variables in the original problem. A global optimal objective is obtained when the lower and upper bounds coincide. The decomposition algorithm guarantees to find an E-optimal solution in a finite number of iterations. In this thesis, several enhanced decomposition methods with improved relaxed master problems are developed, including enhanced NGBD with primal dual information (NGBD-D), piecewise convex relaxation (NGBD-PCR) and lift-and-project cuts (NGBD-LAP). In NGBD-D, additional dual information is introduced into the relaxed master problem by solving the relaxed dual of primal problem. The soobtained primal dual cuts can significantly improve the convergence rate of the algorithm. In NGBD-PCR, the piecewise McCormick relaxation technique is integrated into the NGBD algorithm to reduce the gap between the original problem and its convex relaxation. The domains of variables in bilinear functions can be uniformly partitioned before solution or dynamically partitioned in the algorithm by using the intermediate solution information. In NGBD-LAP, lift-and-project cuts are employed for solving the piecewise lower bounding problem. In all three enhanced decomposition algorithms, there is a trade-off between tighter relaxations and more solution times for subproblems. The computational advantages of the enhanced decomposition methods are demonstrated via case studies on the flexible polygeneration problems. The computational results show that, while NGBD can solve problems that are intractable for a state-ofthe- art global optimization solver (BARON), the enhanced NGBD algorithms help to reduce the solution time by up to an order of magnitude compared to NGBD. And enhanced NGBD algorithms solved the large-scale nonconvex MINLPs to [epsilon]-optimality in practical times (e.g., a problem with 70 binary variables and 44136 continuous variables was solved within 19 hours).by Yang Chen.Ph.D

Multiobjective Early Design of Complex Distillation Sequences Considering Economic and Inherent Safety Criteria

Inherent safety aspects are not usually considered as a driving force during the conceptual design stage of chemical plants. Instead, after the selection of the optimal economic flowsheet, safety is added to the design. However, this sequential design approach could be applied to inferior designs due to protection devices’ cost overrun. The objective of this work is to implement a strategy to simultaneously design a profitable and inherently safer distillation train. Two safety indexes, a disaggregated version of the Safety Weighted Hazard Index and Dow’s Fire and Explosion Index, have been adapted to quantify the inherent safety performance. A large-scale multiobjective MILP problem is formulated. Thus, two strategies of objective reduction are utilized: principal component analysis coupled with Deb’s algorithm and a method based on the dominance structure. The results prove the suitability of these safety index as inherently safer metrics, and showcase the ability of the objective reduction methods to discriminate among the inherent safety criteria.We acknowledge financial support from “Proyectos de I + D para grupos de investigación emergentes GV/2016/005” (Conselleria d’Educació, Investigació, Cultura i Esport, GENERALITAT VALENCIANA) Spanish “Ministerio de Economía, Industria y Competitividad” (CTQ2016-77968-C3-2-P, AEI/FEDER, UE)

Education, biological ageing, all-cause and cause-specific mortality and morbidity : UK biobank cohort study

Background: Socioeconomic position as measured by education may be embodied and affect the functioning of key physiological systems. Links between social disadvantage, its biological imprint, and cause-specific mortality and morbidity have not been investigated in large populations, and yet may point towards areas for public health interventions beyond targeting individual behaviours. Methods: Using data from 366,748 UK Biobank participants with 13 biomarker measurements, we calculated a Biological Health Score (BHS, ranging from 0 to 1) capturing the level of functioning of five physiological systems. Associations between BHS and incidence of cardiovascular disease (CVD) and cancer, and mortality from all, CVD, cancer, and external causes were examined. We explored the role of education in these associations. Mendelian randomisation using genetic evidence was used to triangulate these findings. Findings: An increase in BHS of 0.1 was associated with all-cause (HR = 1.14 [1.12–1.16] and 1.09 [1.07–1.12] in men and women respectively), cancer (HR = 1.11 [1.09–1.14] and 1.07 [1.04–1.10]) and CVD (HR = 1.25 [1.20–1.31] and 1.21 [1.11–1.31]) mortality, CVD incidence (HR = 1.15 [1.13–1.16] and 1.17 [1.15–1.19]). These associations survived adjustment for education, lifestyle-behaviours, body mass index (BMI), co-morbidities and medical treatments. Mendelian randomisation further supported the link between the BHS and CVD incidence (HR = 1.31 [1.21–1.42]). The BHS contributed to CVD incidence prediction (age-adjusted C-statistic = 0.58), other than through education and health behaviours. Interpretation: The BHS captures features of the embodiment of education, health behaviours, and more proximal unknown factors which all complementarily contribute to all-cause, cancer and CVD morbidity and premature death. © 2020 The Author(s)Peer reviewe