Simulation-based reachability analysis for nonlinear systems using componentwise contraction properties

A shortcoming of existing reachability approaches for nonlinear systems is the poor scalability with the number of continuous state variables. To mitigate this problem we present a simulation-based approach where we first sample a number of trajectories of the system and next establish bounds on the convergence or divergence between the samples and neighboring trajectories. We compute these bounds using contraction theory and reduce the conservatism by partitioning the state vector into several components and analyzing contraction properties separately in each direction. Among other benefits this allows us to analyze the effect of constant but uncertain parameters by treating them as state variables and partitioning them into a separate direction. We next present a numerical procedure to search for weighted norms that yield a prescribed contraction rate, which can be incorporated in the reachability algorithm to adjust the weights to minimize the growth of the reachable set

Quantum AdS_5 x S^5 superstring in the AdS light-cone gauge

We consider the AdS_5 x S^5 superstring in the light-cone gauge adapted to a massless geodesic in AdS5 in the Poincare patch. The resulting action has a relatively simple structure which makes it a natural starting point for various perturbative quantum computations. We illustrate the utility of this AdS light-cone gauge action by computing the 1-loop and 2-loop corrections to the null cusp anomalous dimension reproducing in a much simpler and efficient way earlier results obtained in conformal gauge. This leads to a further insight into the structure of the superstring partition function in non-trivial background.Comment: 21pages, Late

Traveling Ionospheric Disturbances in the Vicinity of Storm-Enhanced Density at Midlatitudes

This study provides first storm time observations of the westward-propagating medium-scale traveling ionospheric disturbances (MSTIDs), particularly, associated with characteristic subauroral storm time features, storm-enhanced density (SED), subauroral polarization stream (SAPS), and enhanced thermospheric westward winds over the continental US. In the four recent (2017–2019) geomagnetic storm cases examined in this study (i.e., 2018-08-25/26, 2017-09-07/08, 2017-05-27/28, and 2016-02-02/03 with minimum SYM-H index −206, −146, −142, and −58 nT, respectively), MSTIDs were observed from dusk-to-midnight local times predominately during the intervals of interplanetary magnetic field (IMF) Bz stably southward. Multiple wavefronts of the TIDs were elongated NW-SE, 2°–3° longitude apart, and southwestward propagated at a range of zonal phase speeds between 100 and 300 m/s. These TIDs initiated in the northeastern US and intensified or developed in the central US with either the coincident SED structure (especially the SED basis region) or concurrent small electron density patches adjacent to the SED. Observations also indicate coincident intense storm time electric fields associated with the magnetosphere–ionosphere–thermosphere coupling electrodynamics at subauroral latitudes (such as SAPS) as well as enhanced thermospheric westward winds. We speculate that these electric fields trigger plasma instability (with large growth rates) and MSTIDs. These electrified MSTIDs propagated westward along with the background westward ion flow which resulted from the disturbance westward wind dynamo and/or SAPS

Simultaneous Global Ionospheric Disturbances Associated With Penetration Electric Fields During Intense and Minor Solar and Geomagnetic Disturbances

A new observational phenomenon, named Simultaneous Global Ionospheric Density Disturbance (SGD), is identified in GNSS total electron content (TEC) data during periods of three typical geospace disturbances: a Coronal Mass Ejection-driven severe disturbance event, a high-speed stream event, and a minor disturbance day with a maximum Kp of 4. SGDs occur frequently on dayside and dawn sectors, with a ∼1% TEC increase. Notably, SGDs can occur under minor solar-geomagnetic disturbances. SGDs are likely caused by penetration electric fields (PEFs) of solar-geomagnetic origin, as they are associated with Bz southward, increased auroral AL/AU, and solar wind pressure enhancements. These findings offer new insights into the nature of PEFs and their ionospheric impact while confirming some key earlier results obtained through alternative methods. Importantly, the accessibility of extensive GNSS networks, with at least 6,000 globally distributed receivers for ionospheric research, means that rich PEF information can be acquired, offering researchers numerous opportunities to investigate geospace electrodynamics

<i>C-elegans</i> model identifies genetic modifiers of alpha-synuclein inclusion formation during aging

Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a &lt;i&gt;C-elegans&lt;/i&gt; model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha-synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders

Mechanism of cigarette smoke condensate-induced acute inflammatory response in human bronchial epithelial cells

BACKGROUND: To demonstrate the involvement of tobacco smoking in the pathophysiology of lung disease, the responses of pulmonary epithelial cells to cigarette smoke condensate (CSC) — the particulate fraction of tobacco smoke — were examined. METHODS: The human alveolar epithelial cell line A549 and normal human bronchial epithelial cells (NHBEs) were exposed to 0.4 μg/ml CSC, a concentration that resulted in >90% cell survival and <5% apoptosis. Changes in gene expression and signaling responses were determined by RT-PCR, western blotting and immunocytofluorescence. RESULTS: NHBEs exposed to CSC showed increased expression of the inflammatory mediators sICAM-1, IL-1β, IL-8 and GM-CSF, as determined by RT-PCR. CSC-induced IL-1β expression was reduced by PD98059, a blocker of mitogen-actived protein kinase (MAPK) kinase (MEK), and by PDTC, a NFκB inhibitor. Analysis of intracellular signaling pathways, using antibodies specific for phosphorylated MAPKs (extracellular signal-regulated kinase [ERK]-1/2), demonstrated an increased level of phosphorylated ERK1/2 with increasing CSC concentration. Nuclear localization of phosphorylated ERK1/2 was seen within 30 min of CSC exposure and was inhibited by PD98059. Increased phosphorylation and nuclear translocation of IκB was also seen after CSC exposure. A549 cells transfected with a luciferase reporter plasmid containing a NFκB-inducible promoter sequence and exposed to CSC (0.4 μg/ml) or TNF-α (50 ng/ml) had an increased reporter activity of approximately 2-fold for CSC and 3.5-fold for TNF-α relative to untreated controls. CONCLUSION: The acute phase response of NHBEs to cigarette smoke involves activation of both MAPK and NFκB

Intraluminal migration of a spacer with small bowel obstruction: a case report of rare complication

The spacer placement is a prevalent procedure to separate the surrounding normal tissues from locally recurrent rectal tumor before the application of radiotherapy. However, complications could occur due to the foreign nature of the spacer. This report describes a case of 60-year-old man who had undergone radiotherapy two years earlier for a recurrent rectal tumor and presented with small bowel obstruction. A spacer was used before radiotherapy. Radiological assessment and laparotomy revealed the presence of the spacer inside the small bowel lumen. It is possible that the spacer established contact with the intestine, elicited local inflammatory reaction that facilitated the complete penetration of the intestinal wall without causing any clinical symptoms

A Full Pharmacological Analysis of the Three Turkey β-Adrenoceptors and Comparison with the Human β-Adrenoceptors

There are three turkey β-adrenoceptors: the original turkey β-adrenoceptor from erythrocytes (tβtrunc, for which the X-ray crystal structure has recently been determined), tβ3C and tβ4C-receptors. This study examined the similarities and differences between these avian receptors and mammalian receptors with regards to binding characteristics and functional high and low affinity agonist conformations.Stable cell lines were constructed with each of the turkey β-adrenoceptors and 3H-CGP12177 whole cell binding, CRE-SPAP production and (3)H-cAMP accumulation assays performed. It was confirmed that the three turkey β-adrenoceptors are distinct from each other in terms of amino acid sequence and binding characteristics. The greatest similarity of any of the turkey β-adrenoceptors to human β-adrenoceptors is between the turkey β3C-receptor and the human β2-adrenoceptor. There are pharmacologically distinct differences between the binding of ligands for the tβtrunc and tβ4C and the human β-adrenoceptors (e.g. with CGP20712A and ICI118551). The tβtrunc and tβ4C-adrenoceptors appear to exist in at least two different agonist conformations in a similar manner to that seen at both the human and rat β1-adrenoceptor and human β3-adrenoceptors. The tβ3C-receptor, similar to the human β2-adrenoceptor, does not, at least so far, appear to exist in more than one agonist conformation.There are several similarities, but also several important differences, between the recently crystallised turkey β-adrenoceptor and the human β-adrenoceptors. These findings are important for those the field of drug discovery using the recently structural information from crystallised receptors to aid drug design. Furthermore, comparison of the amino-acid sequence for the turkey and human adrenoceptors may therefore shed more light on the residues involved in the existence of the secondary β-adrenoceptor conformation