1,733 research outputs found
Fighters pilot helmet design for 5th generation aircraft
Fighter pilots’ helmets have become more complex and heavier resulting in long term implications to pilots musculoskeletal systems as they fly and experience high g-load. Current research has identified design changes to the helmet to accommodate the ancillary items fitted to assist pilots but at the expense of comfort and additional loading. Its manufacturing requirements and adaptations to offer bespoke solutions are addressed to allow for training and operational usage. To produce the next generation of helmets that reduce long-term injuries, from g-loads and asymmetrical ancillaries requires individual considerations, unique manufacturing requirements and the ability to support with service spares anywhere in the world at short notice. This paper will describe how manufacturing requirements are matched to ergonomic needs and bespoke components can support global demands
Bridge Build
Bridge build design that includes not only a building process, but a research paper to make the best build possible as well.N/
Studies toward the synthesis of anthraquinone-xanthone heterodimeric natural products
Anthraquinone-xanthone heterodimeric natural products are a diverse family of polyketides highlighted by a unique bicyclo [3.2.2] ring system which links both anthraquinone and xanthone moieties. Both the connectivity of the unique bicyclic ring system and the oxidation state of the two heterocycles vary among the members of this family of natural products. These molecules have been generally isolated as fungal metabolites but also have shown anticoccidial (xanthoquinodin A:0.02 μg/mL), antibiotic (acremonidins A and C; 32 μM and acremoxanthone, MIC; 12.5 μg/mL), and cytotoxicity against various human cancer cell lines. Both anthraquinone and xanthone heterocycles are derived from the anthraquinone chrysophanol, a common biosynthetic intermediate for polyketide synthesis. To date, there have been no reported synthetic efforts or total syntheses of the anthraquinone-xanthone heterodimeric natural products. Related synthetic examples include complex anthraquinone-xanthone biaryls, anthraquinone dimers, and monomeric xanthone and benzophenone-derived natural products.
We describe an initial proposed synthesis wherein we aimed to prepare the unique bicyclo [3.2.2] ring system in a late stage operation of functionalized anthraquinone and xanthone units through a photo-mediated cycloaddition. We achieved synthesis of both an anthraquinone-derived oxanthrone ester fragment and the synthesis of several xanthone related natural products, namely graphisin A, sydowinin B, acremonidin E, and pinselin. Key steps involve aryl anion addition to substituted benzaldehyde derivatives, subsequent methyl ester installation, and dehydrative cyclization. Although we have not yet achieved the desired cycloaddition, we contributed to this area by developing efficient, reliable syntheses of various benzophenone and xanthone natural products.
We will also describe an alternative strategy to access the bicyclo [3.2.2] core of these natural products via various proposed rearrangements of an anthraquinone-xanthone biaryl intermediate. Cross-coupling of substituted xanthone and naphthalene fragments established the desired biaryl linkage which was further elaborated to afford anthraquinone-xanthone biaryl structures. Attempts to rearrange these biaryls are ongoing to produce the unique core structure of the parent natural products.
Initially discovered as a byproduct of the aforementioned cross-coupling reaction, we have achieved homo-coupling of substituted naphthalene fragments. The resulting naphthalene dimers could be further advanced to a series of novel 2,2'-linked anthraquinone dimers including the natural product chrysotalunin
Cyber-Deception and Attribution in Capture-the-Flag Exercises
Attributing the culprit of a cyber-attack is widely considered one of the
major technical and policy challenges of cyber-security. The lack of ground
truth for an individual responsible for a given attack has limited previous
studies. Here, we overcome this limitation by leveraging DEFCON
capture-the-flag (CTF) exercise data where the actual ground-truth is known. In
this work, we use various classification techniques to identify the culprit in
a cyberattack and find that deceptive activities account for the majority of
misclassified samples. We also explore several heuristics to alleviate some of
the misclassification caused by deception.Comment: 4 pages Short name accepted to FOSINT-SI 201
Human Predation Risk Effects On Adult, Male White-Tailed Deer Antipredator Behavior
Recreational hunters play an important role in managing white-tailed deer (Odocoileus virginianus); however, the potential for deer to alter behaviors to avoid hunters has not been addressed within the risk-allocation hypothesis. I evaluated magnitude (i.e., hunter density) and temporal variation (i.e., time of day and initial and prolonged exposure) in human predation risk on movements, resource selection, and observation rates of 37 adult male deer in southern Oklahoma. Deer recognized human predation risk by increasing diel path complexity and use of security cover with greater hunter density. Moreover, deer reduced movement rates and tortuosity while seeking out areas with security cover during prolonged exposure. However, tortuosity and use of security cover remained elevated with greater hunter density. These alterations in behaviors subsequently led to a decrease in observation rates during prolonged exposure. My results clearly support the predation risk-allocation hypothesis by the behavioral responses observed with greater hunter density
Functional and Mechanistic Consequences of Dual Oxidase 1 Suppression in Lung Cancer
The NADPH oxidase homolog, dual oxidase 1 (DUOX1), is an H2O2 producing transmembrane enzyme highly expressed in the airway epithelium. DUOX1-dependent redox signaling has been characterized to regulate many homeostatic processes in the lung epithelium, such as host defense, wound healing, and type II immune responses. Intriguingly, DUOX1 has been found to be suppressed in many epithelial cancers, including lung cancer, by hypermethylation of its promoter. Epigenetic silencing of DUOX1 in cancer is paradoxical to the understanding that tumors harbor elevated levels of reactive oxygen species (ROS), suggesting that DUOX1 may be a tumor suppressor.
Since DUOX1 loss occurs in many forms of lung cancer, we aimed to characterize the functional importance of DUOX1 suppression. RNAi-mediated knockdown of DUOX1 in lung epithelial cells induced features of the epithelial-to-mesenchymal transition (EMT), a characteristic of aggressive or invasive tumor cells. Indeed, DUOX1 suppression promoted the acquisition of molecular signatures associated with EMT, such as the loss of E-cadherin, and induced expression of vimentin and smooth muscle actin. Additionally, we find that DUOX1 suppression promotes the acquisition of other EMT-related features, such as enhanced levels of cancer stem cell molecular markers, cellular invasiveness, and critically, resistance to epidermal growth factor receptor (EGFR) inhibition. Importantly, overexpression of DUOX1 in DUOX1-lacking lung cancer cells promoted the recovery of epithelial characteristics, pinning DUOX1 as a critical mediator of the epithelial phenotype.
Based on prior studies demonstrating DUOX1 as an important regulator of EGFR signaling in the lung epithelium, we hypothesized that DUOX1 loss in lung cancer may impact EGFR regulation. EGFR belongs to a larger family of ErbB receptor tyrosine kinases, which are often overexpressed or mutated in many forms of lung cancer. Surprisingly, we find that lung cancer cells lacking DUOX1 have significantly altered EGFR redox regulation, specifically, kinetically enhanced cysteine oxidation-reduction dynamics. Additionally, our results demonstrate DUOX1-lacking cancer cells have altered intracellular EGFR trafficking with enhanced nuclear targeting. Indeed, we observe many oncogenic features of nuclear EGFR e.g. enhanced migratory capacity, resistance to EGFR blocking antibodies. Finally, we have uncovered that EGFR cysteine redox dynamics may regulate intracellular trafficking and/or nuclear transport, offering potentially novel avenues in the design of therapeutics.
Proper DUOX1 localization and enzymatic function in the plasma membrane requires partnership with its maturation factor, dual oxidase maturation factor 1 (DUOXA1). Preliminary findings from a newly designed DUOX1-DUOXA1 co-expression system suggests that following enzymatic activation of DUOX1, DUOXA1 dissociates from DUOX1 and potentially translocates to the nucleus, a feature not previously described in lung epithelial or cancer cells. While these preliminary results require additional experimentation, this could be a unique regulatory feature of DUOX1 and a novel role for DUOXA1.
Collectively, the research demonstrated in this dissertation characterizes the functional and mechanistic importance of DUOX1 suppression in cancer. Indeed, loss of DUOX1 expression may be an indicator of tumor aggressiveness and responsiveness to EGFR-targeted therapies, warranting its potential for use as a clinical biomarker in lung cancer
Discrete Jordan Curve Theorems
AbstractDiscrete versions of the Jordan Curve Theorem are proved
Right-Sided Sigmoid Diverticular Perforation
Diverticulosis is a common disorder among geriatric patients, of whom 10% to 25% go on to develop diverticulitis. Known complications of diverticulitis include formation of phlegmon, fistula, bowel obstruction, bleeding, perforation, and colonic abscess. A less common complication is perforation with formation of an extra-abdominal necrotizing abscess. This case is a report of an 83-year-old female who presented to the emergency department with a necrotizing abdominal wall abscess secondary to right-sided diverticular microperforation
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