The Isolation of Intragenic Suppressors to Point Mutations In the 3\u27 Coding Region of ftsZ of Streptomyces coelicolor

FtsZ is the earliest known acting protein in the prokaryotic division machine. In Streptomyces coelicolor, mutations in ftsZ result in hyphae that cannot support division and the formation of uninucleoid spores. Part of this study focused on isolating intragenic suppressors to the ftsZ(A275V) mutation to investigate the function of the C-Terminal Domain of the protein. To date, eight intragenic suppressors of A275V have been isolated, three in this study. Their distribution in FtsZ is scattered, although there seems to be a preference for mutations that are near the GTP-binding domain. Also, the function of the highly conserved C-Terminal Core Domain of FtsZ was investigated using a similar strategy, but no intragenic suppressor mutations were isolated. Finally, a development-specific promoter tool was created to allow the expression of an ftsZ allele in aerial filaments alone. One can now express any ftsZ allele to visualize the division phenotype during sporulation septation

The roles of processing, presentation and T cell receptor recognition in the T lymphocyte response to a protein antigen

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 1994.Includes bibliographical references (leaves 126-145).by Alex Szabo.Ph.D

A comparison of the Bravyi-Kitaev and Jordan-Wigner transformations for the quantum simulation of quantum chemistry

The ability to perform classically intractable electronic structure calculations is often cited as one of the principal applications of quantum computing. A great deal of theoretical algorithmic development has been performed in support of this goal. Most techniques require a scheme for mapping electronic states and operations to states of and operations upon qubits. The two most commonly used techniques for this are the Jordan-Wigner transformation and the Bravyi-Kitaev transformation. However, comparisons of these schemes have previously been limited to individual small molecules. In this paper we discuss resource implications for the use of the Bravyi-Kitaev mapping scheme, specifically with regard to the number of quantum gates required for simulation. We consider both small systems which may be simulatable on near-future quantum devices, and systems sufficiently large for classical simulation to be intractable. We use 86 molecular systems to demonstrate that the use of the Bravyi-Kitaev transformation is typically at least approximately as efficient as the canonical Jordan-Wigner transformation, and results in substantially reduced gate count estimates when performing limited circuit optimisations.Comment: 46 pages, 11 figure

Aspects of the foraging ecology of humpback whales (Megaptera novaeangliae) in Frederick Sound and Stephens Passage, Southeast Alaska

The North Pacific humpback whale (Megaptera novaeangliae) population has been increasing at an average annual rate of ~6% since the early 1990s. In northern Southeast Alaska alone, there are now more whales than estimated for the entire North Pacific several decades ago. An understanding of how this growing population is repopulating traditional foraging grounds will benefit from detailed investigations of their prey preferences and trends in whale abundance and distribution relative to those prey. This dissertation examines these issues from late May until early September 2008 in Frederick Sound and Stephens Passage, a Southeast Alaskan feeding area historically used by humpback whales. The foundation for the study is an analysis of the life histories and abundance patterns of euphausiids, the principal prey of humpbacks in the area, during late spring and summer. Four species, Thysanoessa raschii, T. longipes, T. spinifera, and Euphausia pacifica, were identified in plankton net samples collected at random locations throughout the study site (n = 49) and in locations where a strong scattering layer was observed on a 120 kHz echosounder (n = 48). Both sample types varied in euphausiid species composition. Abundance patterns of immature euphausiids coupled with observations of females carrying spermatophores indicated differences between species in spawning schedules. Thysanoessa spp. began spawning in early April with the spring phytoplankton bloom and continued until late June, whereas E. pacifica began spawning in early June and continued until late August. This protracted recruitment of immature euphausiids was geographically widespread throughout the summer in contrast to adults, which, although present all summer, were found primarily in slope and shallow (< 100 m) areas. To determine if humpback whales preferred one euphausiid species or life-stage over another, net sample and hydroacoustic data collected in the vicinity of whales were compared to similar data collected in random locations throughout the study site. This revealed that whales targeted dense aggregations of adult euphausiids, but did not discriminate between the various species, which was surprising because of presumed differences in the energy density linked to their different spawning schedules. Additionally, whales did not spend time in areas with concentrations of immature euphausiids, which were likely not large enough during the study period to be suitable prey. With this preference for adult euphausiids, the abundance and distribution patterns of humpbacks were examined in relation to prey availability. Whale abundance was lowest at the beginning of the study in late May at ca. 68 whales and peaked in late July at ca. 228 animals – approximately 12% of the region’s estimated abundance for the study year. This study did not detect a concomitant increase in the availability of adult euphausiids, which is unsurprising since immature euphausiids would not recruit into the adult population until after the end of the study, and post-spawning mortality and predation pressure is presumably high during this time. Instead, whales clustered increasingly around comparatively fewer prey as the summer progressed. These observations, combined with a plateau in whale abundance after July, suggest that their abundance in the area was limited by euphausiid availability. Estimates of whales using the study site during the summer have remained similar over several decades despite a dramatic increase in humpback numbers in Southeast Alaska and elsewhere in the North Pacific. The results from this study suggest that, although the study site remains important seasonally to some whales, it is not a significant source of prey responsible for regional population growth in general. More likely, it is part of a network of feeding areas that has influenced the population trend. Further insight into these and the other issues raised in this dissertation could come from several additional analyses. An extended sampling season that captures the recruitment of immature euphausiids into the adult population would reveal whether a given year's prey cohort represents an important resource to whales in that same year, which has potential implications for interpreting mid-late season whale abundance patterns. As well, a photo-identification study would be useful in characterizing whale residency patterns and determining whether the abundance trends reflect a relatively small subset of the regional population using the area for most of the season or a continuous flow of a larger portion of the population. Finally, similar analyses as those outlined here but conducted in other areas within the region would provide additional insight into the network’s capacity to support the recovering whale population

Obstacles and Opportunities of Using a Mobile App for Marine Mammal Research

This study investigates the use of a mobile application, Whale mAPP, as a citizen science tool for collecting marine mammal sighting data. In just over three months, 1261 marine mammal sightings were observed and recorded by 39 citizen scientists in Southeast Alaska. The resulting data, along with a preliminary and post-Whale mAPP questionnaires, were used to evaluate the tool’s scientific, educational, and engagement feasibility. A comparison of Whale mAPP Steller sea lion distribution data to a scientific dataset were comparable (91% overlap) given a high enough sample size (n = 73) and dense spatial coverage. In addition, after using Whale mAPP for two weeks, citizen scientists improved their marine mammal identification skills and self-initiated further learning, representing preliminary steps in developing an engaging citizen science project. While the app experienced high initial enthusiasm, maintaining prolonged commitment represents one of the fundamental challenges for this project. Increasing participation with targeted recruitment and sustained communication will help combat the limitations of sample size and spatial coverage. Overall, this study emphasizes the importance of early evaluation of the educational and scientific outcomes of a citizen science project, so that limitations are recognized and reduced

Early Lapita subsistence: the evidence from Kamgot, Anir Islands, New Ireland Province, Papua New Guinea

Over several decades there has been much discussion regarding the nature of Early Lapita subsistence, and in particular whether domesticated animals and horticulture were central components or whether initial Lapita subsistence strategies relied primarily upon marine resources. Here, we assess the evidence for subsistence during the earlier phases of occupation at Kamgot, Anir Islands, New Ireland Province, Papua New Guinea, particularly through the lens of terrestrial versus marine components

Somatostatin Receptors as Molecular Targets in Human Uveal Melanoma

K

Design, synthesis and evaluation of carbamate-linked uridyl-based inhibitors of human ST6Gal I

© 2020 Elsevier Ltd Sialic acid at the terminus of cell surface glycoconjugates is a critical element in cell-cell recognition, receptor binding and immune responses. Sialyltransferases (ST), the enzymes responsible for the biosynthesis of sialylated glycans are highly upregulated in cancer and the resulting hypersialylation of the tumour cell surface correlates strongly with tumour growth, metastasis and drug resistance. Inhibitors of human STs, in particular human ST6Gal I, are thus expected to be valuable chemical tools for the discovery of novel anticancer drugs. Herein, we report on the computationally-guided design and development of uridine-based inhibitors that replace the charged phosphodiester linker of known ST inhibitors with a neutral carbamate to improve pharmacokinetic properties and synthetic accessibility. A series of 24 carbamate-linked uridyl-based compounds were synthesised by coupling aryl and hetaryl α-hydroxyphosphonates with a 5′-amino-5′-deoxyuridine fragment. The inhibitory activities of the newly synthesised compounds against recombinant human ST6Gal I were determined using a luminescent microplate assay, and five promising inhibitors with Ki’s ranging from 1 to 20 µM were identified. These results show that carbamate-linked uridyl-based compounds are a potential new class of readily accessible, non-cytotoxic ST inhibitors to be further explored

Autonomous Combat Robot

This honors project will also serve as an engineering senior design project. The objective is to design and build the software and electrical systems for a 60 lb weight class combat robot that will function autonomously and outperform manually driven robots during competition. While running autonomously, the robot will use LiDAR sensors to detect and attack opponent robots. This robot will also be able to be remote controlled in manual mode. This will mitigate the risk in case the autonomy or sensors fail. LED lights on the robot will indicate whether it is in autonomous or manual mode. The system will also be able to be armed and disarmed remotely. Lastly, the robot will incorporate an emergency shut off and braking system. The autonomous combat robot will outperform its opponents by following a variety of combat algorithms. The autonomous system will follow an intercept or escape locomotion pattern to outperform human operators. The autonomous system will also attempt to keep the robot pointed in the correct orientation, facing the opponent at all times

Joint Assessment of Intended and Unintended Effects of Medications: An Example Using Vascular Endothelial Growth Factor Inhibitors for Neovascular Age-Related Macular Degeneration

Objective. To estimate the net health benefits of pegaptanib and ranibizumab by considering the impact of visual acuity and unintended effects (cardiovascular and hemorrhagic events) on quality-of-life among persons with neovascular age-related macular degeneration. Methods. We designed a probabilistic decision-analytic model using published data. It employed 17 visual health states and three for unintended effects. We calculated incremental net health benefits by subtracting the harms of each medication from the benefit using the quality-adjusted life year (QALY). Results. In a hypothetical cohort of 1,000 75-year olds with new-onset bilateral age-related macular degeneration followed for ten years, the mean QALYs per patient is 3.7 for usual care, 4.2 for pegaptanib, and 4.3 for ranibizumab. Net benefits decline with increasing baseline rates of unintended effects. Interpretation. Net health benefits present a quantitative, potentially useful tool to assist patients and ophthalmologists in balancing the benefits and harms of interventions for age-related macular degeneration