Publications by authors named "Patrick Leslie"

The spectral information contained in the reflective imaging bands can be exploited for specific tasks. Whether targeting or mapping, the visible (VIS), near-infrared (NIR), shortwave infrared (SWIR), extended shortwave infrared (eSWIR) bands perform very differently for every application. For any imaging project, high contrast is very important for good imagery.

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The signal to noise ratio and corresponding visibility of power cables as seen by military aircrafts is critical for crew safety. During low altitude operations, rotorcraft systems must be able to navigate these power lines during flight. Many of these military missions are flown at night which means the reflective bands including the visible, near infrared and short-wave infrared do not provide sufficient light.

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Atmospheric path radiance in the infrared is an extremely important quantity in calculating system performance in certain infrared detection systems. For infrared search and track (IRST) system performance calculations, the path radiance competes with the target for precious detector well electrons. In addition, the radiance differential between the target and the path radiance defines the signal level that must be detected.

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The tumor-suppressor protein p53 is mutated in approximately half of all cancers, whereas the p53 signaling network is perturbed in almost all cancers. In response to different stress stimuli, p53 selectively activates genes to elicit a cell survival or cell death response. How p53 makes the decision between life and death remains a fascinating question and an exciting field of research.

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The prevalence of gambling harm among active duty military personnel is a largely unexplored topic. With different forms of social gambling often found within (or in close proximity to) military bases around the world, understanding the extent of gambling activities and consequent harms occurring within military contexts warrants further attention. This review aims to identify, describe and thematically synthesise published literature on gambling harm and related issues among active duty military personnel.

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Lymph node (LN) metastases correspond with a worse prognosis in nearly all cancers, yet the occurrence of cancer spreading from LNs remains controversial. Additionally, the mechanisms explaining how cancers survive and exit LNs are largely unknown. Here, we show that breast cancer patients frequently have LN metastases that closely resemble distant metastases.

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Angiogenesis is critical to cancer development and metastasis. However, anti-angiogenic agents have only had modest therapeutic success, partly due to an incomplete understanding of tumor endothelial cell (EC) biology. We previously reported that the microRNA (miR)-200 family inhibits metastasis through regulation of tumor angiogenesis, but the underlying molecular mechanisms are poorly characterized.

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Understanding how p53 activates certain gene programs and not others is critical. Here, we identify low-density lipoprotein receptor-related protein 1 (LRP1), a transmembrane endocytic receptor, as a p53 target gene. We show that, although LRP1 transcript expression is upregulated in response to both sub-lethal and lethal doses of p53-activating stress, LRP1 protein is only upregulated in response to sub-lethal stress.

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Lung cancer is the leading cause of cancer-related deaths worldwide, and lung squamous carcinomas (LUSC) represent about 30% of cases. Molecular aberrations in lung adenocarcinomas have allowed for effective targeted treatments, but corresponding therapeutic advances in LUSC have not materialized. However, immune checkpoint inhibitors in sub-populations of LUSC patients have led to exciting responses.

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Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes. p32 is a multicompartmental protein involved in the regulation of oxidative phosphorylation and glucose oxidation. p32 ablation is associated with resistance to age-associated and diet-induced obesity through a mechanism that remains largely unknown.

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Obesity is increasing in prevalence and has become a global public health problem. The main cause of obesity is a perturbation in energy homeostasis, whereby energy intake exceeds energy expenditure. Although mitochondrial dysfunction has been linked to the deregulation of energy homeostasis, the precise mechanism is poorly understood.

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Activation of p53 in response to DNA damage is essential for tumor suppression. Although previous studies have emphasized the importance of p53-dependent cell cycle arrest and apoptosis for tumor suppression, recent studies have suggested that other areas of p53 regulation, such as metabolism and DNA damage repair (DDR), are also essential for p53-dependent tumor suppression. However, the intrinsic connections between p53-mediated DDR and metabolic regulation remain incompletely understood.

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The oncoprotein murine double minute 2 (MDM2) is an E3 ligase that plays a prominent role in p53 suppression by promoting its polyubiquitination and proteasomal degradation. In its active form, MDM2 forms homodimers as well as heterodimers with the homologous protein murine double minute 4 (MDMX), both of which are thought to occur through their respective C-terminal RING (really interesting new gene) domains. In this study, using multiple MDM2 mutants, we show evidence suggesting that MDM2 homo- and heterodimerization occur through distinct mechanisms because MDM2 RING domain mutations that inhibit MDM2 interaction with MDMX do not affect MDM2 interaction with WT MDM2.

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The tumor suppressor p53 has recently been shown to regulate energy metabolism through multiple mechanisms. However, the in vivo signaling pathways related to p53-mediated metabolic regulation remain largely uncharacterized. By using mice bearing a single amino acid substitution at cysteine residue 305 of mouse double minute 2 (Mdm2(C305F)), which renders Mdm2 deficient in binding ribosomal proteins (RPs) RPL11 and RPL5, we show that the RP-Mdm2-p53 signaling pathway is critical for sensing nutrient deprivation and maintaining liver lipid homeostasis.

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Ribosomal proteins (RPs) have gained much attention for their extraribosomal functions particularly with respect to p53 regulation. To date, about fourteen RPs have shown to bind to MDM2 and regulate p53. Upon binding to MDM2, the RPs suppress MDM2 E3 ubiquitin ligase activity resulting in the stabilization and activation of p53.

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Stem cells have emerged as important players in the generation and maintenance of many tissues. However, the accurate in vitro simulation of the native stem cell niche remains difficult due at least in part to the lack of a comprehensive definition of the critical factors of the stem cell niche based on in vivo models. Three-dimensional (3D) cell culture systems have allowed the development of useful models for investigating stem cell physiology particularly with respect to their ability to sense and generate mechanical force in response to their surrounding environment.

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Using current methodologies, drug delivery to small airways, terminal bronchioles, and alveoli (deep lung) is inefficient, especially to the lower lungs. Urgent lung pathologies such as acute respiratory distress syndrome (ARDS) and post-lung transplantation complications are difficult to treat, in part due to the methodological limitations in targeting the deep lung with high efficiency drug distribution to the site of pathology. To overcome drug delivery limitations inhibiting the optimization of deep lung therapy, isolated rat Sertoli cells preloaded with chitosan nanoparticles were use to obtain a high-density distribution and concentration (92%) of the nanoparticles in the lungs of mice by way of the peripheral venous vasculature rather than the more commonly used pulmonary route.

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