Zero outward flow velocity for plasma in a heliosheath transition layer

Voyager 1 has been in the reservoir of energetic ions and electrons that constitutes the heliosheath since it crossed the solar wind termination shock on 16 December 2004 at a distance from the Sun of 94 astronomical units (1?AU = 1.5?×?10(8)?km). It is now ～22?AU past the termination shock crossing. The bulk velocity of the plasma in the radial-transverse plane has been determined using measurements of the anisotropy of the convected energetic ion distribution. Here we report that the radial component of the velocity has been decreasing almost linearly over the past three years, from ～70?km?s(-1) to ～0?km?s(-1), where it has remained for the past eight months. It now seems that Voyager 1 has entered a finite transition layer of zero-radial-velocity plasma flow, indicating that the spacecraft may be close to the heliopause, the border between the heliosheath and the interstellar plasma. The existence of a flow transition layer in the heliosheath contradicts current predictions--generally assumed by conceptual models--of a sharp discontinuity at the heliopause.     

Stabilization of Discrete-Time Dynamical Systems Under Event-Triggered Impulsive Control with and Without Time-Delays

This paper investigates the issue of stabilization for discrete-time dynamical systems (DDS) by event-triggered impulsive control (ETIC). Based on some relatively simple threshold constants, three levels of event conditions are set and thus the ETIC scheme is designed. Three cases for ETIC with and without time-delays and data dropouts are studied respectively, and the criteria on exponential stability are derived for the controlled DDS. The stabilization in the form of exponential stability is achieved for DDS under the designed ETIC with or without time-delays. And in the case of the ETIC data dropouts, the conditions of exponential stabilization are derived for DDS and the maximal allowable dropout rates for ETIC are estimated. Finally, one example with numerical simulations is worked out for illustration.     

COT drives resistance to RAF inhibition through MAP kinase pathway reactivation

Oncogenic mutations in the serine/threonine kinase B-RAF (also known as BRAF) are found in 50-70% of malignant melanomas. Pre-clinical studies have demonstrated that the B-RAF(V600E) mutation predicts a dependency on the mitogen-activated protein kinase (MAPK) signalling cascade in melanoma-an observation that has been validated by the success of RAF and MEK inhibitors in clinical trials. However, clinical responses to targeted anticancer therapeutics are frequently confounded by de novo or acquired resistance. Identification of resistance mechanisms in a manner that elucidates alternative 'druggable' targets may inform effective long-term treatment strategies. Here we expressed ～600 kinase and kinase-related open reading frames (ORFs) in parallel to interrogate resistance to a selective RAF kinase inhibitor. We identified MAP3K8 (the gene encoding COT/Tpl2) as a MAPK pathway agonist that drives resistance to RAF inhibition in B-RAF(V600E) cell lines. COT activates ERK primarily through MEK-dependent mechanisms that do not require RAF signalling. Moreover, COT expression is associated with de novo resistance in B-RAF(V600E) cultured cell lines and acquired resistance in melanoma cells and tissue obtained from relapsing patients following treatment with MEK or RAF inhibitors. We further identify combinatorial MAPK pathway inhibition or targeting of COT kinase activity as possible therapeutic strategies for reducing MAPK pathway activation in this setting. Together, these results provide new insights into resistance mechanisms involving the MAPK pathway and articulate an integrative approach through which high-throughput functional screens may inform the development of novel therapeutic strategies.     

The RNA-binding protein FCA is an abscisic acid receptor

The phytohormone abscisic acid (ABA) regulates various physiological processes in plants. The molecular mechanisms by which this is achieved are not fully understood. Genetic approaches have characterized several downstream components of ABA signalling, but a receptor for ABA has remained elusive. Although studies indicate that several ABA response genes encode RNA-binding or RNA-processing proteins, none has been found to be functional in binding ABA. Here we show that FCA, an RNA-binding protein involved in flowering, binds ABA with high affinity in an interaction that is stereospecific and follows receptor kinetics. The interaction between FCA and ABA has molecular effects on downstream events in the autonomous floral pathway and, consequently, on the ability of the plant to undergo transition to flowering. We further show that ABA binding exerts a direct control on the FCA-mediated processing of precursor messenger RNA. Our results indicate that FCA is an ABA receptor involved in RNA metabolism and in controlling flowering time.     

The accuracy of extrapolation methods; an automatic box–jenkins package sift

Hill and Woodworth (1980) proposed an algorithm suitable for identifying Box–Jenkins models automatically without reliance on the investigator. This paper first reviews the method. It is then used on the 111 series analysed by Anderson in the Makridakis forecasting competition. The results show that the automatic method of Hill and Woodworth is comparable in terms of accuracy to the full Box–Jenkins identification procedure.     

On the participation of the zona glomerulosa on the adrenal response to stress

Zusammenfassung Zwei Serien Ratten wurden durch Formalininjektion belastet. Die Zona glomerulosa der Nebennierenrinde reagierte durch Lipoidausscheidung nur in jener Serie, die durch hohe Lymphozytenzahl des Blutes, hohen Lipoidgehalt der Fasciculata, kleinere Aktivität der Lymphknötchen der Milz und auffallend intensive Stressreaktion der Fasciculata charakterisiert war. Bei Ratten, deren Glomerulosa ihre Lipoide ausgeschieden hatte, trat weder Schwellung noch Desintegration des lymphatischen Gewebes der Milz auf.     

A major susceptibility locus for leprosy in India maps to chromosome 10p13

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is prevalent in India, where about half of the world's estimated 800,000 cases occur. A role for the genetics of the host in variable susceptibility to leprosy has been indicated by familial clustering, twin studies, complex segregation analyses and human leukocyte antigen (HLA) association studies. We report here a genetic linkage scan of the genomes of 224 families from South India, containing 245 independent affected sibpairs with leprosy, mainly of the paucibacillary type. In a two-stage genome screen using 396 microsatellite markers, we found significant linkage (maximum lod score (MLS) = 4.09, P < 2x10-5) on chromosome 10p13 for a series of neighboring microsatellite markers, providing evidence for a major locus for this prevalent infectious disease. Thus, despite the polygenic nature of infectious disease susceptibility, some major, non-HLA-linked loci exist that may be mapped through obtainable numbers of affected sibling pairs.