Real-time Monocular Object SLAM

We present a real-time object-based SLAM system that leverages the largest object database to date. Our approach comprises two main components: 1) a monocular SLAM algorithm that exploits object rigidity constraints to improve the map and find its real scale, and 2) a novel object recognition algorithm based on bags of binary words, which provides live detections with a database of 500 3D objects. The two components work together and benefit each other: the SLAM algorithm accumulates information from the observations of the objects, anchors object features to especial map landmarks and sets constrains on the optimization. At the same time, objects partially or fully located within the map are used as a prior to guide the recognition algorithm, achieving higher recall. We evaluate our proposal on five real environments showing improvements on the accuracy of the map and efficiency with respect to other state-of-the-art techniques

Angiotensin II and Aldosterone Increase with Fasting in Breeding Adult Male Northern Elephant Seals (Mirounga angustirostris)

The renin‐angiotensin‐aldosterone system (RAAS) appears to contribute significantly to osmoregulation of fasting northern elephant seal (Mirounga angustirostris) pups; however, RAAS has not been characterized in fasting adult seals. Therefore, this study examined the contribution of RAAS to water turnover rates in fasting adult male northern elephant seals. Blood samples were obtained twice during their breeding fast at an interval of 6.5 wk, and water efflux rate was estimated by isotopic dilution during the same period. Serum electrolytes (Na+, K+, Cl−) and osmolality were unaltered between the two sampling periods, indicating ionic and osmotic homeostasis during the fast. Despite the lack of an increase in vasopressin, serum angiotensin II and aldosterone were increased and were significantly and positively correlated. Changes in aldosterone concentration and water efflux rate were significantly and negatively correlated, suggesting that the greater the increase in aldosterone, the smaller the loss of water. Adult male seals maintain ionic and osmotic homeostasis similar to that of fasting weaned pups, and this homeostasis appears to be mediated, at least in part, by RAAS, which probably contributes to increased water retention as well. The hormonal mechanisms by which northern elephant seals maintain water and electrolyte balance during fasting conditions appear to be similar regardless of age

Targeting glutathione peroxidases : identifying environmental modulators, and screening for novel small molecule inhibitors

Glutathione peroxidases (GPXs) are a family of selenoproteins that are critical regulators of reactive oxygen species (ROS) in the cell, specifically hydroperoxides like hydrogen peroxide (H2O2). ROS are important for normal cell signaling and are tightly controlled to promote cell growth, proliferation, and survival. Without the antioxidant activity of enzymes like GPXs, however, the oxidative burden in cells can reach a point that leads to DNA damage, carcinogenesis, and eventually cell death. Although this can be catastrophic in early development, as evidenced by knock-out studies, many cancer therapeutics function through manipulating redox balance, suggesting that targeting these enzymes could have therapeutic potential. The modified metabolism of cancer cells can result in increased hydroperoxide production, and GPXs are often overexpressed to compensate for the increased oxidative stress, as well as in cell lines resistant to chemotherapeutics. The studies comprising this thesis examine several aspects of GPX inhibition to better understand how to utilize GPX-targeting agents as potential anti-cancer therapeutics and to identify novel inhibitors for future development. Paper I addresses the effects of environmental heavy metal exposures on the erythrocyte GPX activity in 9-year-old children from the Matlab region of Bangladesh. Samples from 100 children were initially analyzed for concentrations of selenium, arsenic, mercury, and cadmium, as well as C-reactive protein (CRP) using inductively coupled plasma mass spectrometry (ICPMS). GPX1 expression levels in lysed samples were measured using high-throughput immunoblotting, and total GPX activity was measured using a GPX activity assay in lysates. After finding only a slight positive correlation between GPX1 expression and GPX activity, trace elements and CRP levels were considered, and a multivariable-adjusted linear regression analyses was used to assess predictors of GPX activity. Arsenic and CRP levels were significantly negatively associated with active GPX, while not correlated with each other. These results suggest that independently both arsenic exposure and increased CRP levels due to inflammation can suppress GPX activity in erythrocytes. Paper II characterized the off-target inhibition of selenoprotein thioredoxin reductases (TXNRDs) by the ferroptosis inducers, (1S, 3R)RSL3 and ML162. Identified originally in a synthetic lethal screen for compounds specifically cytotoxic to oncogenic RAS, these compounds were then found to induce an iron-dependent cell death via increased lipid peroxidation associated with GPX4-specific inhibition. However, neither compound showed inhibitory activity in biochemical assays using recombinant GPX4, but both show potent inhibition of TXNRD1 in both biochemical and cellular assays. In three cell lines with varying susceptibility to ferroptosis, the cell death induced by RSL3 differed from the cell death caused by more specific TXNRD1 inhibitors, TRi-1 and TRi-2. Specifically, while RSL3 cytotoxicity could be rescued by co-treatment with the ferroptosis suppressor, Fer-1, the cytotoxicity of the Tri compounds was not rescued. Additionally, selenium supplementation diminished the efficacy of RSL3 while the TRi compounds remained unchanged, or slightly more cytotoxic. In all, these studies indicate that the interconnectedness of TXNRD1 and ferroptosis, and furthermore TXNRD1 and GPX4, is complex, but that this important off-target effect needs to be understood to fully characterize the use of these ferroptosis inducers. Paper III established a discovery pipeline for the identification of novel specific inhibitors of GPX1 and GPX4. GR-coupled activity assays using recombinant GPX1 and GPX4 were optimized and miniaturized to 1536-well formats and screened against 12,000 small molecules with annotated mechanisms of action. A suite of confirmational assays were used to ensure specificity: a GR counter-assay was used to identify false-positives in the primary screens; orthogonal endpoint GPX assays were used to confirm inhibitory activity; GPX2 assay was used to further probe specificity of the confirmed active compounds between isoforms; a TXNRD1 assay was used to differentiate small molecules with broad Sec-targeting activity from GPXspecific inhibition; and nano Differential Scanning Fluorimetry (DSF) was used to confirm direct binding. Interestingly, all GPX1 inhibitors identified showed crossinhibition of GPX2. Ultimately, five novel GPX1/GPX2 inhibitors, 13 GPX4 inhibitors, and 2 novel pan-GPX inhibitors. This series of assays and the resulting compounds identified provide a basis for future development of GPX-specific inhibitors. Paper IV profiled the cytotoxicity of a library of >10,000 small molecules with annotated mechanisms of action (MOA) and >100,000 small molecule scaffolds in a diversity library in both normal and cancer cell lines. These screens revealed a low overall cytotoxicity rate of the diversity library. Importantly, cytotoxicity was assessed in four normal cell lines (HEK293, immortalized human embryonic kidney cells; NIH3T3, an embryonic mouse fibroblast cells; HaCat, immortalized human keratinocytes; and CRL-7250, a primary human foreskin fibroblast cells). The top enriched MOA categories showing broad cell killing in normal cells were proteosome inhibitors, heat shock protein 90 (HSP90) inhibitors, anaplastic lymphoma kinase (ALK) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and cyclindependent kinase (CDK) inhibitors. Cytotoxic compounds with specific activity against the human adenosarcoma cancer line, KB 3-1, that showed no activity in the normal cell lines were also highlighted. This work will be used as an additional triage step in lead-selection for chemotherapeutic development, removing compounds that show significant cytotoxicity in normal cell lines

Hormone and Metabolite Changes associated with Extended Breeding Fasts in Male Northern Elephant Seals (Mirounga Angustirostris)

We measured metabolic hormones and several key metabolites in breeding adult male northern elephant seals to examine the regulation of fuel metabolism during extended natural fasts of over 3 months associated with high levels of energy expenditure. Males were sampled twice, early and late in the fast, losing an average of 23% of body mass and 47% of adipose stores between measurements. Males exhibited metabolic homeostasis over the breeding fast with no changes in glucose, non-esterified fatty acids, or blood urea nitrogen. Ketoacids increased over the fast but were very low when compared to other fasting species. Changes within individuals in total triiodothyronine (tT3) were positively related to daily energy expenditure (DEE) and protein catabolism. Differences in levels of thyroid hormones relative to that observed in weaned pups and females suggest a greater deiodination of T4 to support the high DEE of breeding males. Relative levels of leptin and ghrelin were consistent with the suppression of appetite but a significant reduction in growth hormone across the fast was contrary to expectation in fasting mammals. The lack of the increase in cortisol during fasting found in conspecific weaned pups and lactating females may contribute to the ability of breeding males to spare protein despite high levels of energy expenditure. Together these findings reveal significant differences with conspecifics under varying nutrient demands, suggesting metabolic adaptation to extended high energy fasts

Renal Function in Suckling and Fasting Pups of the Northern Elephant Seal

Elephant seals fast for prolonged periods without access to water. This is made possible, in part, by reductions in urine production. However, the mechanisms involved in reducing urine production are not understood. In this study, glomerular filtration rate (GFR) was measured in five northern elephant seal pups (Mirounga angustirostris) via the inulin clearance technique. Measurements were made during day 9 and day 18–22 of nursing and the second and eighth week of the postweaning fast. Plasma aldosterone and cortisol concentrations, quantified by radioimmunoassay, were measured in eight other weanlings during the second and eighth week of the fast. Mean GFR was 79.3±29.3 ml/min during the early suckling period and 78.2±17.1, 89.8±52.7, and 80.4±12.2 ml/min during the late suckling, early fasting and late fasting periods, respectively. Differences between nursing and fasting were insignificant, possibly because reduced protein oxidation during suckling and rapid recruitment of protein for tissue synthesis obviated the need for postprandial hyperfiltration. Alternatively, maintenance of GFR during fasting may facilitate urea concentration by compensating for reductions in the fractional excretion of urea. It is further hypothesized that aldosterone is primarily responsible for mediating renal water reabsorption in this system

Technologies for trapped-ion quantum information systems

Scaling-up from prototype systems to dense arrays of ions on chip, or vast networks of ions connected by photonic channels, will require developing entirely new technologies that combine miniaturized ion trapping systems with devices to capture, transmit and detect light, while refining how ions are confined and controlled. Building a cohesive ion system from such diverse parts involves many challenges, including navigating materials incompatibilities and undesired coupling between elements. Here, we review our recent efforts to create scalable ion systems incorporating unconventional materials such as graphene and indium tin oxide, integrating devices like optical fibers and mirrors, and exploring alternative ion loading and trapping techniques.Comment: 19 pages, 18 figure