636 research outputs found
The Stability and Control of Stochastically Switching Dynamical Systems
Inherent randomness and unpredictability is an underlying property in most realistic phenomena. In this work, we present a new framework for introducing stochasticity into dynamical systems via intermittently switching between deterministic regimes. Extending the work by Belykh, Belykh, and Hasler, we provide analytical insight into how randomly switching network topologies behave with respect to their averaged, static counterparts (obtained by replacing the stochastic variables with their expectation) when switching is fast. Beyond fast switching, we uncover a highly nontrivial phenomenon by which a network can switch between two asynchronous regimes and synchronize against all odds. Then, we establish rigorous theory for this framework in discrete-time systems for arbitrary switching periods (not limited to switching at each time step). Using stability and ergodic theories, we are able to provide analytical criteria for the stability of synchronization for two coupled maps and the ability of a single map to control an arbitrary network of maps. This work not only presents new phenomena in stochastically switching dynamical systems, but also provides the first rigorous analysis of switching dynamical systems with an arbitrary switching period
A Matter of Accountability: Communication and Coordination Failures Proceeding Pearl Harbor
Abstract
Save for September 11, 2001, arguably no other incident in American history generates persistent and impassioned debate associated with the questions of why and on whom to affix responsibility than does the Pearl Harbor raid. For both Japan and the United States the road to December 7 (or 8th in Japan), was long and complex. Ensconced within the context of what was underway in Europe, there existed little room for diplomatic miscalculations or missteps. Thus for American civil, military, naval, and diplomatic leaders in Washington, D.C. and throughout the world, that American installations were attacked should not have been, and to varying degrees were not taken aback. Most surprising then from the American perspective was the place and how that attack happened. So again, how did the U.S. Army and Navy in Hawaii render themselves such an inviting target in the late fall of 1941?
Keywords: Roosevelt, Yamamoto, Kimmel, Short, Pearl Harbo
Calamitous Pursuit: The Fetterman Fight
Since that fateful December day in which Captain William Fetterman, two civilians, and 78 officers and men were annihilated in the present-day state of Wyoming, culpability has rested entirely with that officer. The oft- reason for this disastrous result is that Fetterman was effectively a reckless officer that dismissed out-of-hand the martial capabilities of warriors from the Sioux, Cheyenne, and Arapahoe tribes. This derogatory opinion therefore, led to his leading the task force placed under his command on December 21, 1866 into an ambush and wholescale death to every soldier and civilian
Democracy and Dysfunction: Rural Electric Cooperatives and the Surprising Persistence of the Separation of Ownership and Control
Since the 1930s, corporate law scholarship has focused narrowly on the public corporation and the problem of the separation of ownership and control-a problem many now believe has been mitigated or even solved. With rare exceptions, scholars have paid far less heed to other business forms that still play important roles in the American economy. In this Article, we examine a significant and almost completely overlooked business form, the Rural Electric Cooperative (REC). RECs were founded in a moment of optimism during the New Deal. As with other cooperatives, their organizational rules differed sharply from those of for-profit corporations. They were owned by their customers, with each customer-member having one vote irrespective of their energy consumption, and it was hoped these owners would provide active oversight of the REC\u27s managers and activities. Reality has proven otherwise. Corporate governance innovations of the last forty years have passed RECs by, leaving an organizational sector mired in governance dysfunctions stemming from the separation of ownership and control. Here we explain why RECs evolved as they did and why New Deal planners seized on the cooperative form to electrify the countryside; how significant governance problems have persisted, largely unaddressed, from the 1930s to today; and how a change in corporate governance rules, allowing for a market for corporate control in RECs, could fix some persistent problems in this still-important sector. Alternatively, we propose that RECs take up a new public role as rural broadband internet providers with a reinvigorated federal regulator to police governance failures
The cancer gene WWOX behaves as an inhibitor of SMAD3 transcriptional activity via direct binding
Background: The WW domain containing protein WWOX has been postulated to behave as a tumor suppressor in breast and other cancers. Expression of this protein is lost in over 70% of ER negative tumors. This prompted us to investigate the phenotypic and gene expression effects of loss of WWOX expression in breast cells.
Methods: Gene expression microarrays and standard in vitro assays were performed on stably silenced WWOX (shRNA) normal breast cells. Bioinformatic analyses were used to identify gene networks and transcriptional regulators affected by WWOX silencing. Co-immunoprecipitations and GST-pulldowns were used to demonstrate a direct interaction between WWOX and SMAD3. Reporter assays, ChIP, confocal microscopy and in silico analyses were employed to determine the effect of WWOX silencing on TGFβ-signaling.
Results: WWOX silencing affected cell proliferation, motility, attachment and deregulated expression of genes involved in cell cycle, motility and DNA damage. Interestingly, we detected an enrichment of targets activated by the SMAD3 transcription factor, including significant upregulation of ANGPTL4, FST, PTHLH and SERPINE1 transcripts. Importantly, we demonstrate that the WWOX protein physically interacts with SMAD3 via WW domain 1. Furthermore, WWOX expression dramatically decreases SMAD3 occupancy at the ANGPTL4 and SERPINE1 promoters and significantly quenches activation of a TGFβ responsive reporter. Additionally, WWOX expression leads to redistribution of SMAD3 from the nuclear to the cytoplasmic compartment. Since the TGFβ target ANGPTL4 plays a key role in lung metastasis development, we performed a meta-analysis of ANGPTL4 expression relative to WWOX in microarray datasets from breast carcinomas. We observed a significant inverse correlation between WWOX and ANGPTL4. Furthermore, the WWOX lo/ANGPTL4hi cluster of breast tumors is enriched in triple-negative and basal-like sub-types. Tumors with this gene expression signature could represent candidates for anti-TGFβ targeted therapies.
Conclusions: We show for the first time that WWOX modulates SMAD3 signaling in breast cells via direct WW-domain mediated binding and potential cytoplasmic sequestration of SMAD3 protein. Since loss of WWOX expression increases with breast cancer progression and it behaves as an inhibitor of SMAD3 transcriptional activity these observations may help explain, at least in part, the paradoxical pro-tumorigenic effects of TGFβ signaling in advanced breast cancer.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicada
Disparities in hypertension and cardiovascular disease in blacks: The critical role of medication adherence
Blacks are two to three times as likely as whites to die of preventable heart disease and stroke. Declines in mortality from heart disease have not eliminated racial disparities. Control and effective treatment of hypertension, a leading cause of cardiovascular disease, among blacks is less than in whites and remains a challenge. One of the driving forces behind this racial/ethnic disparity is medication nonadherence whose cause is embedded in social determinants. Eight practical approaches to addressing medication adherence with the potential to attenuate disparities were identified and include: (1) patient engagement strategies, (2) consumer-directed health care, (3) patient portals, (4) smart apps and text messages, (5) digital pillboxes, (6) pharmacist-led engagement, (7) cardiac rehabilitation, and (8) cognitive-based behavior. However, while data suggest that these strategies may improve medication adherence, the effect on ameliorating racial/ethnic disparities is not certain. This review describes the relationship between disparities and medication adherence, which likely plays a role in persistent disparities in cardiovascular morbidity and mortality
The Advanced Automated Directional Solidification Furnace
The Advanced Automated Directional Solidification Furnace (AADSF) is a five zone tubular furnace designed for Bridgman-Stockbarger, other techniques of crystal growth involving multiple temperature zones such as vapor transport experiments and other materials science experiments. The five zones are primarily designed to produce uniform hot and cold temperature regions separated by an adiabatic region constructed of a heat extraction plate and an insert to reduce radiation from the hot to the cold zone. The hot and cold zone temperatures are designed to reach 1600 C and 1100 C, respectively. AADSF operates on a Multi-Purpose Experiment Support Structure (MPESS) within the cargo bay of the Space Shuttle on the United States Microgravity Payload (USMP) missions. Two successful flights, both employing the directional solidification or Bridgman Stockbarger technique for crystal growth have been made, and crystals of HgCdTe and PbSnTe grown in microgravity have been produced on USMP-2 and USMP-3, respectively. The addition of a Sample Exchange Mechanism (SEM) will enable three different samples to be processed on future flights including the USMP-4 mission
WWOX P47T partial loss-of-function mutation induces epilepsy, progressive neuroinflammation, and cerebellar degeneration in mice phenocopying human SCAR12
WWOX gene loss-of-function (LoF) has been associated with neuropathologies resulting in developmental, epileptic, and ataxic phenotypes of varying severity based on the level of WWOX dysfunction. WWOX gene biallelic germline variant p.Pro47Thr (P47T) has been causally associated with a new form of autosomal recessive cerebellar ataxia with epilepsy and intellectual disability (SCAR12, MIM:614322). This mutation affecting the WW1 protein binding domain of WWOX, impairs its interaction with canonical proline-proline-X-tyrosine motifs in partner proteins. We generated a mutant knock-in mouse model of Wwox P47T mutation that phenocopies human SCAR12. WwoxP47T/P47T mice displayed epilepsy, profound social behavior and cognition deficits, and poor motor coordination, and unlike KO models that survive only for 1 month, live beyond 1 year of age. These deficits progressed with age and mice became practically immobile, suggesting severe cerebellar dysfunction. WwoxP47T/P47T mice brains revealed signs of progressive neuroinflammation with elevated astro-microgliosis that increased with age. Cerebellar cortex displayed significantly reduced molecular and granular layer thickness and a strikingly reduced number of Purkinje cells with degenerated dendrites. Transcriptome profiling from various brain regions of WW domain LoF mice highlighted widespread changes in neuronal and glial pathways, enrichment of bioprocesses related to neuroinflammation, and severe cerebellar dysfunction. Our results show significant pathobiological effects and potential mechanisms through which WWOX partial LoF leads to epilepsy, cerebellar neurodegeneration, neuroinflammation, and ataxia. Additionally, the mouse model described here will be a useful tool to understand the role of WWOX in common neurodegenerative conditions in which this gene has been identified as a novel risk factor.Fil: Hussain, Tabish. University of Texas; Estados UnidosFil: Sanchez, Kevin. University of Texas at Austin; Estados UnidosFil: Crayton, Jennifer. University of Texas; Estados UnidosFil: Saha, Dhurjhoti. University of Texas; Estados UnidosFil: Jeter, Collene. University of Texas; Estados UnidosFil: Lu, Yue. University of Texas; Estados UnidosFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Seo, Ryan. Baylor College of Medicine; Estados UnidosFil: Noebels, Jeffrey L.. Baylor College of Medicine; Estados UnidosFil: Fonken, Laura. University of Texas at Austin; Estados UnidosFil: Aldaz, C. Marcelo. University of Texas; Estados Unido
Geometric origin of mechanical properties of granular materials
Some remarkable generic properties, related to isostaticity and potential
energy minimization, of equilibrium configurations of assemblies of rigid,
frictionless grains are studied. Isostaticity -the uniqueness of the forces,
once the list of contacts is known- is established in a quite general context,
and the important distinction between isostatic problems under given external
loads and isostatic (rigid) structures is presented. Complete rigidity is only
guaranteed, on stability grounds, in the case of spherical cohesionless grains.
Otherwise, the network of contacts might deform elastically in response to load
increments, even though grains are rigid. This sets an uuper bound on the
contact coordination number. The approximation of small displacements (ASD)
allows to draw analogies with other model systems studied in statistical
mechanics, such as minimum paths on a lattice. It also entails the uniqueness
of the equilibrium state (the list of contacts itself is geometrically
determined) for cohesionless grains, and thus the absence of plastic
dissipation. Plasticity and hysteresis are due to the lack of such uniqueness
and may stem, apart from intergranular friction, from small, but finite,
rearrangements, in which the system jumps between two distinct potential energy
minima, or from bounded tensile contact forces. The response to load increments
is discussed. On the basis of past numerical studies, we argue that, if the ASD
is valid, the macroscopic displacement field is the solution to an elliptic
boundary value problem (akin to the Stokes problem).Comment: RevTex, 40 pages, 26 figures. Close to published paper. Misprints and
minor errors correcte
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