Computational Studies of Fully Submerged Bodies, Propulsors, and Body/Propulsor Interactions

Difficulties exist with designing and testing on a model scale. The purpose of this study is to examine variations in the flow field of a submarine due to hull/propulsor interaction and Reynolds scaling. The scope of this study includes the simulation of the flow past a 1) five-bladed marine propeller with 0° skew, 2) unappended submarine hull, 3) forward propelled submarine with asymmetrical stern appendages, and 4) submarine in crashback with asymmetrical stern appendages. The bare hull simulations are conducted for three different length scales: small model scale, large model scale, and full scale. The isolated propeller and appended submarine simulations are conducted on the large model scale. It is of interest how sensitive the various flow characteristics are to Reynolds number and the turbulence model. All simulations are at 0° angle of attack, and validated with experimental data where available

Aging an Ancient Maya Population from Actuncan, Belize using Dental X-Rays

My goal is to determine an accurate age at death estimation of an ancient Maya population from the archaeological site of Actuncan, Belize. This was done by measuring the lengths of the coronal pulp cavities in the individuals’ teeth. I used X-Ray images to measure the coronal pulp cavities of the teeth and estimated age using multiple regression formulae for premolars, molars, and incisors to make age estimations. The formulae came from two studies, Ikeda et al. (1985) and Drusini (2008), that form the basis of my research. Ikeda et al. (1985) was the first to use this aging method, while Drusini’s (2008) research closely follows the Ikeda et al. (1985) method using a new population. The measurements on the Actuncan population were measured by myself, a peer Eden Irwin, and Dr. Carolyn Freiwald. The results were inconsistent, some that clearly were errors. These inconsistencies are largely due to lack of a tooth-wear scale to base the teeth on, third-party X-Rays, formulae from multiple articles, and measuring program sensitivity. Overall, the age estimations fell within the 20 - 50 year age range. This research is important because age-at-death is the basis for understanding ancient health and longevity in archaeological populations and for use in forensic applications

Mapping proteolytic processing in the secretome of gastric cancer-associated myofibroblasts reveals activation of MMP-1, MMP-2, and MMP-3

Cancer progression involves changes in extracellular proteolysis, but the contribution of stromal cell secretomes to the cancer degradome remains uncertain. We have now defined the secretome of a. specific stromal cell type, the rnyofibroblast, in gastric cancer and its modification by proteolysis. SILAC labeling and COFRADIC isolation of methionine containing peptides allowed us to quantify differences in gastric cancer-derived myofibroblasts compared with myofibroblasts from adjacent tissue, revealing increased abundance of several proteases in cancer myofibroblasts including matrix metalloproteinases (MMP)-1 and -3. Moreover, N-terminal COFRADIC analysis identified cancer-restricted proteolytic cleavages, including liberation of the active forms of MMP-1, -2, and -3 from their inactive precursors. In vivo imaging confirmed increased MMP activity when gastric cancer cells were xenografted in mice together with gastric cancer myofibroblasts. Western blot and enzyme activity assays confirmed increased MMP-1, -2, and -3 activity in cancer myofibroblasts, and cancer cell migration assays indicated stimulation by MMP-1, -2, and -3 in cancer-associated rnyofibroblast media. Thus, cancer-derived myofibroblasts differ from their normal counterparts by increased production and activation of MMP-1, -2, and -3, and this may contribute to the remodelling of the cancer cell microenvironment

Fatty acid ethyl ester synthase inhibition ameliorates ethanol-induced Ca2+-dependent mitochondrial dysfunction and acute pancreatitis

Objective Non-oxidative metabolism of ethanol (NOME) produces fatty acid ethyl esters (FAEEs) via carboxylester lipase (CEL) and other enzyme action implicated in mitochondrial injury and acute pancreatitis (AP). This study investigated the relative importance of oxidative and non-oxidative pathways in mitochondrial dysfunction, pancreatic damage and development of alcoholic AP, and whether deleterious effects of NOME are preventable. Design Intracellular calcium ([Ca2+]C), NAD(P)H, mitochondrial membrane potential and activation of apoptotic and necrotic cell death pathways were examined in isolated pancreatic acinar cells in response to ethanol and/or palmitoleic acid (POA) in the presence or absence of 4-methylpyrazole (4-MP) to inhibit oxidative metabolism. A novel in vivo model of alcoholic AP induced by intraperitoneal administration of ethanol and POA was developed to assess the effects of manipulating alcohol metabolism. Results Inhibition of OME with 4-MP converted predominantly transient [Ca2+]C rises induced by low ethanol/POA combination to sustained elevations, with concurrent mitochondrial depolarisation, fall of NAD(P)H and cellular necrosis in vitro. All effects were prevented by 3-benzyl-6-chloro-2-pyrone (3-BCP), a CEL inhibitor. 3-BCP also significantly inhibited rises of pancreatic FAEE in vivo and ameliorated acute pancreatic damage and inflammation induced by administration of ethanol and POA to mice. Conclusions A combination of low ethanol and fatty acid that did not exert deleterious effects per se became toxic when oxidative metabolism was inhibited. The in vitro and in vivo damage was markedly inhibited by blockade of CEL, indicating the potential for development of specific therapy for treatment of alcoholic AP via inhibition of FAEE generation

Baseline microglial activation correlates with brain amyloidosis and longitudinal cognitive decline in Alzheimer disease

BACKGROUND AND OBJECTIVES: This study aims to quantify microglial activation in individuals with Alzheimer disease (AD) using the 18-kDa translocator protein (TSPO) PET imaging in the hippocampus and precuneus, the 2 AD-vulnerable regions, and to evaluate the association of baseline neuroinflammation with amyloidosis, tau, and longitudinal cognitive decline. METHODS: Twenty-four participants from the Knight Alzheimer Disease Research Center (Knight ADRC) were enrolled and classified into stable cognitively normal, progressor, and symptomatic AD groups based on clinical dementia rating (CDR) at 2 or more clinical assessments. The baseline TSPO radiotracer [11C]PK11195 was used to image microglial activation. Baseline CSF concentrations of Aβ42, Aβ42/Aβ40 ratio, tau phosphorylated at position 181 (p-tau181), and total tau (t-tau) were measured. Clinical and cognitive decline were examined with longitudinal CDR and cognitive composite scores (Global and Knight ADRC-Preclinical Alzheimer Cognitive Composite [Knight ADRC-PACC] Score). RESULTS: Participants in the progressor and symptomatic AD groups had significantly elevated [11C]PK11195 standard uptake value ratios (SUVRs) in the hippocampus but not in the precuneus region. In the subcohort with CSF biomarkers (16 of the 24), significant negative correlations between CSF Aβ42 or Aβ42/Aβ40 and [11C]PK11195 SUVR were observed in the hippocampus and precuneus. No correlations were observed between [11C]PK11195 SUVR and CSF p-tau181 or t-tau at baseline in those regions. Higher baseline [11C]PK11195 SUVR averaged in the whole cortical regions predicted longitudinal decline on cognitive tests. DISCUSSION: Microglial activation is increased in individuals with brain amyloidosis and predicts worsening cognition in AD. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with AD, higher baseline [11C]PK11195 SUVR averaged in the whole cortical regions was associated with longitudinal decline on cognitive tests

Measurement of diets that are healthy, environmentally sustainable, affordable, and equitable: A scoping review of metrics, findings, and research gaps

IntroductionResearch on the impacts of dietary patterns on human and planetary health is a rapidly growing field. A wide range of metrics, datasets, and analytical techniques has been used to explore the role of dietary choices/constraints in driving greenhouse gas (GHG) emissions, environmental degradation, health and disease outcomes, and the affordability of food baskets. Many argue that each domain is important, but few have tackled all simultaneously in analyzing diet-outcome relationships.MethodsThis paper reviews studies published between January 2015 and December 2021 (inclusive) that examined dietary patterns in relation to at least two of the following four thematic pillars: (i) planetary health, including, climate change, environmental quality, and natural resource impacts, (ii) human health and disease, (iii) economic outcomes, including diet cost/affordability, and (iv) social outcomes, e.g., wages, working conditions, and culturally relevant diets. We systematically screened 2,425 publications by title and abstract and included data from 42 eligible publications in this review.ResultsMost dietary patterns used were statistically estimated or simulated rather than observed. A rising number of studies consider the cost/affordability of dietary scenarios in relation to optimized environmental and health outcomes. However, only six publications incorporate social sustainability outcomes, which represents an under-explored dimension of food system concerns.DiscussionThis review suggests a need for (i) transparency and clarity in datasets used and analytical methods; (ii) explicit integration of indicators and metrics linking social and economic issues to the commonly assessed diet-climate-planetary ecology relationships; (iii) inclusion of data and researchers from low- and middle-income countries; (iv) inclusion of processed food products to reflect the reality of consumer choices globally; and (v) attention to the implications of findings for policymakers. Better understanding is urgently needed on dietary impacts on all relevant human and planetary domains simultaneously