Thyroid-hormone therapy and thyroid cancer: a reassessment.

Experimental studies and clinical data have demonstrated that thyroid-cell proliferation is dependent on thyroid-stimulating hormone (TSH), thereby providing the rationale for TSH suppression as a treatment for differentiated thyroid cancer. Several reports have shown that hormone-suppressive treatment with the L-enantiomer of tetraiodothyronine (L-T(4)) benefits high-risk thyroid cancer patients by decreasing progression and recurrence rates, and cancer-related mortality. Evidence suggests, however, that complex regulatory mechanisms (including both TSH-dependent and TSH-independent pathways) are involved in thyroid-cell regulation. Indeed, no significant improvement has been obtained by suppressing TSH in patients with low-risk thyroid cancer. Moreover, TSH suppression implies a state of subclinical thyrotoxicosis. In low-risk patients, the goal of L-T(4) treatment is therefore to obtain a TSH level in the normal range (0.5-2.5 mU/l). Only selected patients with high-risk papillary and follicular thyroid cancer require long-term TSH-suppressive doses of L-T(4). In these patients, careful monitoring is necessary to avoid undesirable effects on bone and heart

Cooling of rocket thrust chambers with liquid oxygen

Rocket engines using high pressure liquid oxygen (LOX) and kerosene (RP-1) as the propellants have been considered for future launch vehicle propulsion. Generally, in regeneratively cooled engines, the fuel is used to cool the combustion chamber. However, hydrocarbons such as RP-1 are limited in their cooling capability at high temperatures and pressures. Therefore, LOX is being considered as an alternative coolant. However, there has been concern as to the effect on the integrity of the chamber liner if oxygen leaks into the combustion zone through fatigue cracks that may develop between the cooling passages and the hot-gas side wall. To address this concern, an investigation was previously conducted with simulated fatigue cracks upstream of the thrust chamber throat. When these chambers were tested, an unexpected melting in the throat region developed which was not in line with the simulated fatigue cracks. The current experimental program was conducted in order to determine the cause for the failure in the earlier thrust chambers and to further investigate the effects of cracks in the thrust chamber liner upstream of the throat. The thrust chambers were tested at oxygen-to-fuel mixture ratios from 1.5 to 2.86 at a nominal chamber pressure of 8.6 MPa. As a result of the test series, the reason for the failure occurring in the earlier work was determined to be injector anomalies. The LOX leaking through the simulated fatigue cracks did not affect the integrity of the chambers

Characterization of MSWI fly ashes along the flue gas cooling path and implications on heavy metal recovery through acid leaching

This study reports on detailed chemical and mineralogical characterization of the different municipal solid waste incineration ashes forming along the flue gas path of plants with separate dust removal and neutralization. In pursuit of optimizing heavy metal recovery through acid leaching, the metal extractability from empty pass ashes (EA), boiler ashes (BOA) and the electrostatic precipitator ashes (ESPA) was evaluated and compared. The focus was laid on matrix phases affecting leachability (e.g. alkalinity, oxidation–reduction potential), as well as on distribution and concentration of recoverable heavy metals and their binding forms. The data showed, that EA and BOA are geochemically similar and are essentially composed of two different materials: the heavy metal poor airborne ash particles and the Zn- and Pb-rich sulfate deposits that condensate on heat exchanger surfaces. Variation in relative amount and chemical composition of the deposits is responsible for fluctuations in bulk composition of EA and BOA. The ESPA shows different chemical and mineralogical characteristics than EA and BOA. The ESPA is enriched in the volatile heavy metals Zn, Pb, Cu, Cd and Sn, which are mainly incorporated in chlorides and sulfates. The high content of salt-bound and thus easily soluble heavy metals together with the lower alkalinity and lower oxidation–reduction potential indicates, that ESPA has a better leachability compared to EA and BOA. The EA and BOA, on the other hand, do not show any significant differences in leachability. The data may contribute to a basis for re-evaluating disposal routes of ash fractions with poor extraction properties

Dual action of a dinoflagellate-derived precursor of Pacific ciguatoxins (P-CTX-4B) on voltage-dependent K(+) and Na(+) channels of single myelinated axons

The effects of Pacific ciguatoxin-4B (P-CTX-4B, also named gambiertoxin), extracted from toxic Gambierdiscus dinoflagellates, were assessed on nodal K(+) and Na(+) currents of frog myelinated axons, using a conventional voltage-clamp technique. P-CTX-4B decreased, within a few minutes, both K(+) and Na(+) currents in a dose-dependent manner, without inducing any marked change in current kinetics. The toxin was more effective in blocking K(+) than Na(+) channels. P-CTX-4B shifted the voltage-dependence of Na(+) conductance by about 14 mV towards more negative membrane potentials. This effect was reversed by increasing Ca(2+) in the external solution. A negative shift of about 16 mV in the steady-state Na(+) inactivation-voltage curve was also observed in the presence of the toxin. Unmodified and P-CTX-4B-modified Na(+) currents were similarly affected by the local anaesthetic lidocaine. The decrease of the two currents by lidocaine was dependent on both the concentration and the membrane potential during pre-pulses. In conclusion, P-CTX-4B appears about four times more effective than P-CTX-1B to affect K(+) channels, whereas it is about 50 times less efficient to affect Na(+) channels of axonal membranes. These actions may be related to subtle differences between the two chemical structures of molecules

Developing a framework for the assessment of current and future flood risk in Venice, Italy

Flooding causes serious impacts on the old town of Venice, its residents, and its cultural heritage. Despite this existence-defining condition, limited scientific knowledge on flood risk of the old town of Venice is available to support decisions to mitigate existing and future flood impacts. Therefore, this study proposes a risk assessment framework to provide a methodical and flexible instrument for decision-making for flood risk management in Venice. We first use a state-of-the-art hydrodynamic urban model to identify the hazard characteristics inside the city of Venice. Exposure, vulnerability, and corresponding damage are then modeled by a multi-parametric, micro-scale damage model which is adapted to the specific context of Venice with its dense urban structure and high risk awareness. Furthermore, a set of individual protection scenarios are implemented to account for possible variability in flood preparedness of the residents. This developed risk assessment framework was tested for the flood event of 12 November 2019 and proved able to reproduce flood characteristics and resulting damage well. A scenario analysis based on a meteorological event like 12 November 2019 was conducted to derive flood damage estimates for the year 2060 for a set of sea level rise scenarios in combination with a (partially) functioning storm surge barrier, the Modulo Sperimentale Elettromeccanico (MOSE). The analysis suggests that a functioning MOSE barrier could prevent flood damage for the considered storm event and sea level scenarios almost entirely. A partially closed MOSE barrier (open Lido inlet) could reduce the damage by up to 34 % for optimistic sea level rise prognoses. However, damage could be 10 % to 600 % higher in 2060 compared to 2019 for a partial closure of the storm surge barrier, depending on different levels of individual protection.</p

Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction