Massive Spin 3/2 Electrodynamics

We study the general non-minimally coupled charged massive spin 3/2 model both for its low energy phenomenological properties and for its unitarity, causality and degrees of freedom behaviour. When the model is viewed as an effective theory, its parameters (after ensuring the correct excitation count) are related to physical characteristics, such as the magnetic moment g factor, by means of low energy theorems. We also provide the corresponding higher spin generalisation. Separately, we consider both low and high energy unitarity, as well as the causality aspects of our models. None (including truncated N=2 supergravity) is free of the minimal model's acausality.Comment: 23 pages, 1 figure, LaTeX and axodraw.sty, novel Majorana-type term included; results unaltere

Modeling ocean-cryosphere interactions off Adélie and George V Land, East Antarctica

Ocean–cryosphere interactions along the Adélie and George V Land (AGVL) coast are investigated using a coupled ocean–sea ice–ice shelf model. The dominant feature of the Mertz Glacier Tongue (MGT), located at approximately 145°E, was a highly productive winter coastal polynya system, until its calving in February 2010 dramatically changed the regional “icescape.” This study examines the annual mean, seasonal, and interannual variabilities of sea ice production; basal melting of the MGT; ice shelves, large icebergs, and fast ice; Dense Shelf Water (DSW) export; and bottom water properties on the continental slope and rise, and assesses the impacts of the calving event. The interannual variability of the winter coastal polynya regime is dominated by the regional offshore winds and air temperature, which are linked to activity of the Amundsen Sea low pressure system. This is the main driver of the interannual variability of DSW exported from the AGVL region. The calving event led to a decrease in sea ice production that resulted in a decrease in the density of DSW export. Subsequently, there is extensive freshening downstream over the continental shelf and slope regions. In addition, it is found that the calving event causes a significant decrease in the mean melt rate of the MGT, resulting from a decrease in ocean heat flux into the cavity due to ocean circulation changes

A novel finding of a low-molecular-weight compound, SMTP-7, having thrombolytic and anti-inflammatory effects in cerebral infarction of mice

Tissue plasminogen activator (t-PA) has a short therapeutic time window for administration (3 h) and carries a risk of promoting intracerebral hemorrhage. The aim of the present study was to investigate a therapeutic time window and frequency of hemorrhagic region by treatment with Stachybotrys microspora triprenyl phenol-7 (SMTP-7). Thrombotic occlusion was induced by transfer of acetic acid-induced thrombus at the right common carotid artery into the brain of mice. Infarction area, neurological score, edema percentage, and regional cerebral blood flow (CBF) were determined as the index of the efficacy of SMTP-7. In order to evaluate the mechanism of SMTP-7, plasmin activities and the expressions of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-6 mRNA were examined. SMTP-7 (0.1, 1, 10 mg/kg) dose dependently reduced infarction area, neurological score, and edema percentage. Additionally, its therapeutic time window was longer than that of t-PA, a high-molecular-weight compound. In addition, little hemorrhagic region was induced by treatment with SMTP-7. SMTP-7 showed plasmin activity in vivo and caused a decreased CBF to recover. Furthermore, the expressions of inflammatory cytokine mRNA (IL-1β, TNF-α, IL-6) were increased by t-PA treatment 3 h after ischemia but were not induced by SMTP-7 treatment. These results indicate that SMTP-7 shows potential thrombolytic and anti-inflammatory effects as well as a wide therapeutic time window and little hemorrhagic region compared with that of t-PA. Therefore, this novel low-molecular-weight compound may represent a novel approach for the treatment of cerebral infarction

A role for North Pacific salinity in stabilizing North Atlantic climate

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 22 (2007): PA3102, doi:10.1029/2007PA001420.A simple ocean/atmosphere feedback may reduce the amplitude of climate variability in around the North Atlantic during interglacial compared to glacial states. When climate is warm in the North Atlantic region, the Intertropical Convergence Zone has a relatively northward position, and moisture is exported from the tropical Atlantic to the tropical Pacific. At the same time the east Asian summer monsoon is strong, which helps maintain a positive balance of precipitation over evaporation in the subpolar North Pacific. This is thought to account for lower salinity in the North Pacific relative to the North Atlantic, which, in turn, drives northward flow through the Bering Strait to the northern North Atlantic. Freshening in the North Atlantic by water of Pacific origin suppresses the meridional overturning circulation and reduces the heat flux. The opposite situation exists during cold climate. Thus the combination of atmospheric vapor transport and flow through Bering Strait tends to cool the North Atlantic region when warm and warm the region when cool.Ideas presented in this paper were developed while surveying and coring in the Panama Basin to reconstruct the history of salinity and ITCZ changes (OCE0317702) and in the Bering and Chukchi seas to study the role of sea level and Bering Strait in climate change (OPP9912122). M.S.C. was funded by Oak Foundation to participate on the Chukchi Sea expedition

Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer

Background:Sunitinib malate (SUTENT) has promising single-agent activity given on Schedule 4/2 (4 weeks on treatment followed by 2 weeks off treatment) in advanced non-small cell lung cancer (NSCLC).Methods:We examined the activity of sunitinib on a continuous daily dosing (CDD) schedule in an open-label, multicentre phase II study in patients with previously treated, advanced NSCLC. Patients ⩾18 years with stage IIIB/IV NSCLC after failure with platinum-based chemotherapy, received sunitinib 37.5 mg per day. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), 1-year survival rate, and safety.Results:Of 47 patients receiving sunitinib, one patient achieved a confirmed partial response (ORR 2.1% (95% confidence interval (CI) 0.1, 11.3)) and 11 (23.4%) had stable disease (SD) ⩾8 weeks. Five patients had SD>6 months. Median PFS was 11.9 weeks (95% CI 8.6, 14.1) and median OS was 37.1 weeks (95% CI 31.1, 69.7). The 1-year survival probability was 38.4% (95% CI 24.2, 52.5). Treatment was generally well tolerated.Conclusions:The safety profile and time-to-event analyses, albeit relatively low response rate of 2%, suggest single-agent sunitinib on a CDD schedule may be a potential therapeutic agent for patients with advanced, refractory NSCLC

Inactivation of the FLCN Tumor Suppressor Gene Induces TFE3 Transcriptional Activity by Increasing Its Nuclear Localization

Germline mutations in a tumor suppressor gene FLCN lead to development of fibrofolliculomas, lung cysts and renal cell carcinoma (RCC) in Birt-Hogg-Dubé syndrome. TFE3 is a member of the MiTF/TFE transcription factor family and Xp11.2 translocations found in sporadic RCC involving TFE3 result in gene fusions and overexpression of chimeric fusion proteins that retain the C-terminal DNA binding domain of TFE3. We found that GPNMB expression, which is regulated by MiTF, was greatly elevated in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Since TFE3 is implicated in RCC, we hypothesized that elevated GPNMB expression was due to increased TFE3 activity resulting from the inactivation of FLCN.TFE3 knockdown reduced GPNMB expression in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Moreover, FLCN knockdown induced GPNMB expression in FLCN-restored renal cancer cells. Conversely, wildtype FLCN suppressed GPNMB expression in FLCN-null cells. FLCN inactivation was correlated with increased TFE3 transcriptional activity accompanied by its nuclear localization as revealed by elevated GPNMB mRNA and protein expression, and predominantly nuclear immunostaining of TFE3 in renal cancer cells, mouse embryo fibroblast cells, mouse kidneys and mouse and human renal tumors. Nuclear localization of TFE3 was associated with TFE3 post-translational modifications including decreased phosphorylation.Increased TFE3 activity is a downstream event induced by FLCN inactivation and is likely to be important for renal tumor development. This study provides an important novel mechanism for induction of TFE3 activity in addition to TFE3 overexpression resulting from Xp11.2 translocations, suggesting that TFE3 may be more broadly involved in tumorigenesis

Folliculin interacts with p0071 (plakophilin-4) and deficiency is associated with disordered rhoa signalling, epithelial polarization and cytokinesis

Inherited mutations in the folliculin (FLCN) gene cause the Birt-Hogg-Dubé syndrome of familial hair follicle tumours (fibrofolliculomas), lung cysts and kidney tumours. Though folliculin has features of a tumour suppressor, the precise function of the FLCN gene product is not well characterized. We identified plakophilin-4 (p0071) as a potential novel folliculin interacting protein by yeast two-hybrid analysis. We confirmed the interaction of folliculin with p0071 by co-immunoprecipitation studies and, in view of previous studies linking p0071 to the regulation of rho-signalling, cytokinesis and intercellular junction formation, we investigated the effect of cell folliculin status on p0071-related functions. Folliculin and p0071 partially co-localized at cell junctions and in mitotic cells, at the midbody during cytokinesis. Previously, p0071 has been reported to regulate RhoA signalling during cytokinesis and we found that folliculin deficiency was associated with increased expression and activity of RhoA and evidence of disordered cytokinesis. Treatment of folliculin-deficient cells with a downstream inhibitor of RhoA signalling (the ROCK inhibitor Y-27632) reversed the increased cell migration phenotype observed in folliculin-deficient cells. Deficiency of folliculin and of p0071 resulted in tight junction defects and mislocalization of E-cadherin in mouse inner medullary collecting duct-3 renal tubular cells. These findings suggest that aspects of folliculin tumour suppressor function are linked to interaction with p0071 and the regulation of RhoA signalling

K201 (JTV-519) alters the spatiotemporal properties of diastolic Ca2+ release and the associated diastolic contraction during β-adrenergic stimulation in rat ventricular cardiomyocytes

K201 has previously been shown to reduce diastolic contractions in vivo during β-adrenergic stimulation and elevated extracellular calcium concentration ([Ca2+]o). The present study characterised the effect of K201 on electrically stimulated and spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca2+ release and contractile events in isolated rat cardiomyocytes during β-adrenergic stimulation and elevated [Ca2+]o. Parallel experiments using confocal microscopy examined spontaneous diastolic Ca2+ release events at an enhanced spatiotemporal resolution. 1.0 μmol/L K201 in the presence of 150 nmol/L isoproterenol (ISO) and 4.75 mmol/L [Ca2+]o significantly decreased the amplitude of diastolic contractions to ~16% of control levels. The stimulated free Ca2+ transient amplitude was significantly reduced, but stimulated cell shortening was not significantly altered. When intracellular buffering was taken into account, K201 led to an increase in action potential-induced SR Ca2+ release. Myofilament sensitivity to Ca2+ was not changed by K201. Confocal microscopy revealed diastolic events composed of multiple Ca2+ waves (2–3) originating at various points along the cardiomyocyte length during each diastolic period. 1.0 μmol/L K201 significantly reduced the (a) frequency of diastolic events and (b) initiation points/diastolic interval in the remaining diastolic events to 61% and 71% of control levels respectively. 1.0 μmol/L K201 can reduce the probability of spontaneous diastolic Ca2+ release and their associated contractions which may limit the propensity for the contractile dysfunction observed in vivo

Quantization of an interacting spin-3/2 field and the Delta isobar

Quantization of the free and interacting Rarita-Schwinger field is considered using the Hamiltonian path-integral formulation. The particular interaction we study in detail is the \pi N \De coupling used in the phenomenology of the pion-nucleon and nucleon-nucleon systems. Within the Dirac constraint analysis, we show that there is an excess of degrees of freedom in the model, as well as the inconsistency related to the Johnson-Sudarshan-Velo-Zwanzinger problem. It is further suggested that couplings invariant under the gauge transformation of the Rarita-Schwinger field are generally free from these inconsistencies. We then construct and briefly analyse some lowest in derivatives gauge-invariant \pi N \De couplings.Comment: 20 pages, published versio