A Nanoscale Parametric Feedback Oscillator

We describe and demonstrate a new oscillator topology, the parametric feedback oscillator (PFO). The PFO paradigm is applicable to a wide variety of nanoscale devices and opens the possibility of new classes of oscillators employing innovative frequency-determining elements, such as nanoelectromechanical systems (NEMS), facilitating integration with circuitry and system-size reduction. We show that the PFO topology can also improve nanoscale oscillator performance by circumventing detrimental effects that are otherwise imposed by the strong device nonlinearity in this size regime

"Making Safety Happen" Through Probabilistic Risk Assessment at NASA

NASA is using Probabilistic Risk Assessment (PRA) as one of the tools in its Safety & Mission Assurance (S&MA) tool belt to identify and quantify risks associated with human spaceflight. This paper discusses some of the challenges and benefits associated with developing and using PRA for NASA human space programs. Some programs have entered operation prior to developing a PRA, while some have implemented PRA from the start of the program. It has been observed that the earlier a design change is made in the concept or design phase, the less impact it has on cost and schedule. Not finding risks until the operation phase yields much costlier design changes and major delays, which can result in discussions of just accepting the risk. Risk contributors identified by PRA are not just associated with hardware failures. They include but are not limited to crew fatality due to medical causes, the environment the vehicle and crew are exposed to, the software being used, and the reliability of the crew performing required actions. Some programs have entered operation prior to developing a PRA, and while PRA can still provide a benefit for operations and future design trades, the benefit of implementing PRA from the start of the program provides the added benefit of informing design and reducing risk early in program development. Currently, NASAs International Space Station (ISS) program is in its 20th year of on-orbit operations around the Earth and has several new programs in the design phase preparing to enter the operation phase all of which have active (or living) PRAs. These programs incorporate PRA as part of their Risk-Informed, Decision-Making (RIDM) process. For new NASA human spaceflight programs discussion begins with mission concept, establishing requirements, forming the PRA team, and continues through the design cycles into the operational phase. Several examples of PRA related applications and observed lessons are included

Nonlinear Competition Between Small and Large Hexagonal Patterns

Recent experiments by Kudrolli, Pier and Gollub on surface waves, parametrically excited by two-frequency forcing, show a transition from a small hexagonal standing wave pattern to a triangular ``superlattice'' pattern. We show that generically the hexagons and the superlattice wave patterns bifurcate simultaneously from the flat surface state as the forcing amplitude is increased, and that the experimentally-observed transition can be described by considering a low-dimensional bifurcation problem. A number of predictions come out of this general analysis.Comment: 4 pages, RevTex, revised, to appear in Phys. Rev. Let

Modeling the Risk of U.S. Offshore Oil & Gas Exploration-Well Drilling, Commercial Nuclear Plants, and Human Spaceflight

Probabilistic Risk Assessment (PRA) has been applied in different industries for many years. Each industry and technology area presents varying challenges and priorities, and the risk models therefore need to be somewhat different. This paper compares aspects of risk modeling of offshore drilling, nuclear plant operation, and human spaceflight. Risk models in all three technology areas have certain high-level similarities: (1) they employ redundancy and diversity in their means to prevent or mitigate risk, including a mix of active and passive systems designed to respond to off-normal evolutions; (2) they are affected by human reliability; (3) their models require consideration of coupling between scenario structure and scenario phenomenology. But in examining the models in more detail, one sees important differences in methodology and emphasis. For purposes of comparison, this paper discusses aspects of a risk model of an offshore drilling operation in the U.S. Gulf of Mexico, focusing on where such a development differs in important ways from models of commercial U.S. nuclear plants and models developed for human spaceflight

Unicompartmental Knee Arthroplasty Is Associated with a Lower Rate of Periprosthetic Joint Infection Compared to Total Knee Arthroplasty

Background: Several studies have reported lower perioperative complications with unicompartmental knee arthroplasty (UKA) than with total knee arthroplasty (TKA). However, there is a paucity of data analyzing the incidence of periprosthetic joint infection (PJI) in similar patients undergoing UKA and TKA. As such, we sought to analyze the incidence of UKA and TKA PJI in a large matched population. Material and Methods: The Mariner data set of the PearlDiver database was queried for all patients undergoing UKA or TKA during 2010-2017. Included patients were required to have at least 2 years of database inclusion after surgery. Patients were then matched at a 1:3 ratio (UKA:TKA) on age, gender, Elixhauser Comorbidity Index, tobacco use, and obesity. Rates of PJI requiring operative intervention within 90 days and 1 year were calculated. Results: In total, 5636 patients having undergone UKA were matched to 16,890 patients having undergone TKA. Fifteen (0.27%) after UKA and 79 (0.47%) after TKA had a PJI surgically managed within 90 days (risk ratio = 0.57, 95% confidence interval = 0.33-0.99, P = .04). Thirty (0.53%) after UKA and 136 (0.81%) after TKA had a PJI surgically managed within 1 year (risk ratio = 0.66, 95% confidence interval = 0.45-0.98, P = .04). Conclusions: In a large group of rigorously matched patients, UKA was associated with a significantly lower rate of surgically managed PJI than TKA at 90 days and 1 year; however, the rate of PJI in both groups remained low at \u3c 1% at 90 days and 1 year

Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Tobacco use is the main risk factor for HNSCC, and tobacco-associated HNSCCs have poor prognosis and response to available treatments. Recently approved anti-PD-1 immune checkpoint inhibitors showed limited activity (≤20%) in HNSCC, highlighting the need to identify new therapeutic options. For this, mouse models that accurately mimic the complexity of the HNSCC mutational landscape and tumor immune environment are urgently needed. Here, we report a mouse HNSCC model system that recapitulates the human tobacco-related HNSCC mutanome, in which tumors grow when implanted in the tongue of immunocompetent mice. These HNSCC lesions have similar immune infiltration and response rates to anti-PD-1 (≤20%) immunotherapy as human HNSCCs. Remarkably, we find that >70% of HNSCC lesions respond to intratumoral anti-CTLA-4. This syngeneic HNSCC mouse model provides a platform to accelerate the development of immunotherapeutic options for HNSCC

Convective Fingering of an Autocatalytic Reaction Front

We report experimental observations of the convection-driven fingering instability of an iodate-arsenous acid chemical reaction front. The front propagated upward in a vertical slab; the thickness of the slab was varied to control the degree of instability. We observed the onset and subsequent nonlinear evolution of the fingers, which were made visible by a {\it p}H indicator. We measured the spacing of the fingers during their initial stages and compared this to the wavelength of the fastest growing linear mode predicted by the stability analysis of Huang {\it et. al.} [{\it Phys. Rev. E}, {\bf 48}, 4378 (1993), and unpublished]. We find agreement with the thickness dependence predicted by the theory.Comment: 11 pages, RevTex with 3 eps figures. To be published in Phys Rev E, [email protected], [email protected], [email protected]

Nerves are more abundant than blood vessels in the degenerate human intervertebral disc

Chronic low back pain (LBP) is the most common cause of disability worldwide. New ideas surrounding LBP are emerging that are based on interactions between mechanical, biological and chemical influences on the human IVD. The degenerate IVD is proposed to be innervated by sensory nerve fibres and vascularised by blood vessels, and it is speculated to contribute to pain sensation. However, the incidence of nerve and blood vessel ingrowth, as well as whether these features are always associated, is unknown. We investigated the presence of nerves and blood vessels in the nucleus pulposus (NP) of the IVD in a large population of human discs

Onset of Surface-Tension-Driven Benard Convection

Experiments with shadowgraph visualization reveal a subcritical transition to a hexagonal convection pattern in thin liquid layers that have a free upper surface and are heated from below. The measured critical Marangoni number (84) and observation of hysteresis (3%) agree with theory. In some experiments, imperfect bifurcation is observed and is attributed to deterministic forcing caused in part by the lateral boundaries in the experiment.Comment: 4 pages. The RevTeX file has a macro allowing various styles. The appropriate style is "mypprint" which is the defaul

Class 3 semaphorins expression and association with innervation and angiogenesis within the degenerate human intervertebral disc

Nerve and blood vessel ingrowth during intervertebral disc degeneration, is thought to be a major cause of low back pain, however the regulation of this process is poorly understood. Here, we investigated the expression and regulation of a subclass of axonal guidance molecules known as the class 3 semaphorins, and their receptors; plexins and neuropilins within human NP tissue and their regulation by pro-inflammatory cytokines. Importantly this determined whether semaphorin expression was associated with the presence of nerves and blood vessels in tissues from human intervertebral discs. The study demonstrated that semaphorin3A, 3C, 3D, 3E and 3F and their receptors were expressed by native NP cells and further demonstrated their expression was regulated by IL-1β but to a lesser extent by IL-6 and TNFα. This is the first study to identify sema3C, sema3D and their receptors within the nucleus pulposus of intervertebral discs. Immunopositivity shows significant increases in semaphorin3C, 3D and their receptor neuropilin-2 in degenerate samples which were shown to contain nerves and blood vessels, compared to non-degenerate samples without nerves and blood vessels. Therefore data presented here suggests that semaphorin3C may have a role in promoting innervation and vascularisation during degeneration, which may go on to cause low back pain