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Abstract Stable acquisitions of metabolism, such as the endosymbiotic incorporation of eukaryotic chloroplasts, are thought to proceed through mechanisms that increase the genetic repertoire of the host and allow for vertical integration of new metabolism. Here we test these predictions using the chloroplast-stealing marine ciliate genus Mesodinium by comparing transcriptomes from species that represent a spectrum from full heterotrophy to nearly full phototrophy. In contrast to theory, we find a striking divestment in metabolic autonomy with increased reliance on acquired photosynthesis. Indeed, the highly photosynthetic, red tide-forming Mesodinium rubrum appears to have lost the capacity to synthesize amino acids, metabolize fatty acids, and produce peroxisomes. Our results portray a metabolic parasite, masquerading as a free-living ciliate, yet incapable of satisfying most of its basic anabolic needs.

ABSTRACT Isoniazid (INH) is a critical antibiotic used worldwide for treatment and prophylaxis of tuberculosis. Drug resistance (DR) to INH is the single most common type of DR, mediated by multiple genes/loci including katG, inhA, mabA, mabA-inhA and the oxyR-ahpC intergenic region. Over the course of 6 years, we performed a 2-phase study of 3,696 Mycobacterium tuberculosis complex (MTBC) strains aiming to determine the molecular basis of INH resistance and assess whole genome sequencing (WGS) for predicting resistance. In phase 1, we performed a side-by-side study including 1,767 strains with paired phenotypic drug susceptibility testing (DST) and genotypic DST. We found WGS capable of accurately predicting INH resistance with sensitivity of 90.3%, and specificity of 99.8%. The negative predictive value of WGS for INH susceptibility was 98.8%. Based on these findings, we developed a molecular testing algorithm where phenotypic DST was reduced and applied this new testing algorithm in phase 2 to 1,929 MTBC strains, resulting in streamlined testing, reduced cost and decreasing turnaround time (TAT). The prevalence of INH resistance among MTBC strains in New York was found to be 10.2%. Of the 3,696 isolates tested, 337 were predicted INH resistant by WGS. Of 41 additional strains exhibiting phenotypic INH resistance, 38 were found to have mutations in genes known to be associated with INH resistance. This study demonstrates the utility of WGS as a molecular tool for predicting INH DR and shows that the vast majority of INH resistance in MTBC has a molecular basis in known resistance loci.

Abstract Broadly protective immunity to the Lyme disease spirochete,Borreliella burgdorferi, is constrained by an overwhelming antibody response against type-specific epitopes on Outer surface protein C (OspC), a homodimeric helix-rich lipoprotein essential for early stages of spirochete dissemination in vertebrate hosts. However, the molecular basis for type-specific immunity has not been fully elucidated. In this report, we produced and characterized an OspC mouse monoclonal antibody, 8C1, that recognizes native and recombinant OspC type A (OspCA) but not OspC types B or K, and arrestsB. burgdorferimotility independent of complement. Epitope mapping by HDX-MS localized 8C1’s epitope to a protruding ridge on the apex of OspCAα-helix 3 (residues 130-150) previously known to be an immunodominant region of the molecule. Alanine scanning pinpointed 8C1’s core binding motif to a solvent exposed patch consisting of residues K141H142T143D144. In parallel, analysis of 26 Lyme disease positive serum samples confirmed antibody reactivity with this region of OspCA, with residues E140and D144as being most consequential. Our results underscore the importance of α-helix 3 as a target of type-specific epitopes on OspCAacross mice and humans that should be taken into consideration in Lyme disease vaccine design.

Rara vez le llega a la arquitectura su obsolescencia funcional. Lo habitual es el desencanto: una obsoles- cencia del entusiasmo que desvela el agotamiento emocional de sus habitantes, de un grupo cultural o de toda una sociedad. Frente a las narraciones que describen la obsolescencia como un estado previo a la refundacio?n, cabe pensar en esta como un estado de multiplicidad que resulta de la coexistencia de vidas proyectadas en torno a un mismo objeto construido. Revertir una de esas obsolescencias puede suponer acabar con la existencia del otro. Desde esta perspectiva es posible idear una estrategia proyectual no binaria que plantee una coexistencia ma?s compleja y asime?trica. En el caso que aqui? nos trae, los an?os vivi- deros de la casa Farnsworth, esa posibilidad surge de la concepcio?n de una arquitectura blanda, subversiva y cri?tica, capaz de aceptar la complejidad de su permanente agotamiento y su constante reinvencio?n.

To ensure the sustainable use of one of West Virginia’s precious resources, conscientious long-term management of residual waste is of immense importance. This thesis examined two main topics: i) the dewatering process of acid mine drainage (AMD) sludge, and ii) an investigation of soil loss predictions of a reclaimed coal refuse impoundment. The first aspect of this thesis addresses clarification and remediation of AMD prior to disposal is a prominent component to preventing runoff and seepage of environmentally detrimental byproducts. To examine the effects of flocculation and dewatering more closely by means of geotextiles, an AMD sludge was analyzed. The raw AMD was sourced from the underground mine, treated by precipitation at an approximate pH of 3.2, and clarified to a pH of 6.7 using calcium hydroxide (lime). The supernatant is settled through a series of ponds. Then the sludge produced during the clarification process was dredged, flocculated with polymers concentrated at 20 ppm to create filterable flock, and dewatered through a series of geotextile tubes. Following the dewatering process, geotechnical property testing was performed in accordance with ASTM International Standards to determine the predominately lean, elastic silt soil characteristics of the sludge. The second component utilizes the USDA’s Water Erosion Prediction Project (WEPP), a process-based computer modeling program created to anticipate soil displacement, loss, and deposition during singular or continuous storm events, was utilized to evaluate the runoff and sediment loss of a reclaimed coal refuse impoundment. To identify the unique characteristics of the impoundment, field measurements of infiltration, ground cover, and soil samples were completed and analyzed. Using TR-55 single storm predictions, the annual soil loss was predicted to be 0.397 tons for a two-year return period, 0.661 tons for a five-year return period, 0.879 tons for a 10-year return period, 1.245 tons during a 25-year return period, 1.588 tons from a 50-year event, 1.922 tons during a 100-year event, and finally a total of 2.525 tons of soil lost during a 500-year return event from the impoundment. Due to the minimal slope (i.e., 2.4%) it can be predicted that the impoundment will not experience substantial amounts of soil loss for the foreseeable future as long as vegetation is maintained.

Detection of antibodies in the blood is an important clinical technique for diagnosing active infections and previous exposures. The grating-coupled fluorescent plasmonics (GC-FP) biosensing platform has been used to detect Lyme disease serum antibodies in patients and has been shown to be more sensitive than the current standard tests. In this study, we sought to design an affordable GC-FP detection system without sacrificing the sensitivity of data output. We further optimized our analysis strategies to achieve highly sensitive and consistent diagnostic results. This work ultimately aims to fill an unmet need for better detection of human Lyme disease.

You’ve compared notes, assessed, and researched the programs, and you’ve drafted your people into the integration process as team leads and team players. You have your goals and your milestones set and your strategy and timeline in place. You’ve completed all the necessary legwork, now it’s time to get started with execution. Implementation is a very exciting step in the process as you’ll begin to see the results of all of your hard work. In this chapter, Greg kicks things off with an outline of how leaders can help guide the integration and implementation process through communication and organization, then hands off to Shaun for his approach to working with the different teams for execution.

Metal loss caused by selective leaching of aluminum (referred to herein as dealloying) in certain aluminum-bronze (Al-Brz) alloys is an environmentally-induced degradation mechanism in piping systems containing cast components exposed to marine, brackish, or raw water service. Examples of this form of degradation have been observed in ASME Code Class 3 Essential Cooling Water systems. Mechanical properties for tensile strength and fracture toughness of Al-Brz static and centrifugal castings, fabricated to ASME SB-148 CA952 and CA954 specifications, can locally degrade in service due to dealloying under long exposure to aggressive water environments. This paper presents the results on the reduction in mechanical strength as a result of dealloying. A mechanical testing program was completed where 20 tensile and 22 fracture toughness specimens were tested to determine the reduction in mechanical properties from no dealloying (virgin condition) to various amounts of dealloying up to 100% dealloyed condition measured across the specimen. The specimens were fabricated from components removed from service (some components being in service for over 25 years). The data were plotted as a function of percent dealloying where a systematic decrease in properties was seen directly dependent the amount of dealloyed material in the cross-section of the specimen.

Unemployment among older adults during recessionary cycles has been tied to early retirement decisions and negative health outcomes. This study explored episodes of unemployment experienced between age 50 and retirement as predictors of retirement age and health outcomes. A total of 1540 participants from the U.S. Health and Retirement Study aged 50 years and older who transitioned from workforce to retirement were analyzed with descriptive statistics and multiple regression controlling for unemployment, demographics, and health status. Late-life unemployment significantly related to earlier retirement age and lowered life satisfaction, independent of income effects. We found no main effect for late-life unemployment on physical health status. Potential improvements in future life satisfaction might be gained if job search obstacles are removed for older unemployed adults, reducing reliance on involuntary early retirement as an income source.