ALBERT

Description: Advanced head and neck squamous cell cancer (HNSCC) is currently treated with taxane-based chemotherapy. We have previously shown that docetaxel (DTX) induces a ras-dependent survival signal that can be antagonized by farnesyl transferase inhibitors (FTI) such as tipifarnib (TIP). Here we show that the synergistic TIP/DTX combination determines synergistic apoptotic conditions but, at the same time, it modulates the expression of the components of the multichaperone complex that is, in turn, involved in the regulation of the stability of members of the ras-mediated pathway. Therefore, we have stably transfected HNSCC KB and Hep-2 cells with a plasmid encoding for HSP90. The expression of the protein was increased in both transfected cell lines but its activation status was increased in Hep-2 clones and decreased in KB clones. On the basis of these results, we have treated both parental and HSP90-transfected cells with a HSP90 inhibitor geldanamycin (GA). We have found that the antiproliferative activity of GA is dependent upon the activation status of HSP90 and that it is strongly synergistic when added in combination with TIP but not with DTX in cells overexpressing HSP90 and even more in cells with increased HSP90 activity. These data were paralleled by the decreased expression and activity of the components belonging to the ras→mediated signal transduction pathway. The present results suggest that multichaperone complex activation could be a resistance mechanism to the anti-proliferative and apoptotic effects induced by TIP and that the combination of FTIs such as TIP with GA could be a suitable therapeutic strategy in the treatment of HSP90-overexpressing HNSCC. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.

Description: We perform a retrospective forecast experiment on the 1992 Landers sequence comparing the predictive power of commonly used model frameworks for short-term earthquake forecasting. We compare a modified short-term earthquake probability (STEP) model, six realizations of the epidemic-type aftershock sequence (ETAS) model, and four models that combine Coulomb stress changes calculations and rate-and-state theory to generate seismicity rates (CRS models). We perform the experiment under the premise of a controlled environment with predefined conditions for the testing region and data for all modelers. We evaluate the forecasts with likelihood tests to analyze spatial consistency and the total amount of forecasted events versus observed data. We find that (1) 9 of the 11 models perform superior compared to a simple reference model, (2) ETAS models forecast the spatial evolution of seismicity best and perform best in the entire test suite, (3) the modified STEP model matches best the total number of events, (4) CRS models can only compete with empirical statistical models by introducing stochasticity in these models considering uncertainties in the finite-fault source model, and (5) resolving Coulomb stress changes on 3-D optimally oriented planes is more adequate for forecasting purposes than using the specified receiver fault concept. We conclude that statistical models perform generally better than the tested physics-based models and parameter value updates using the occurrence of aftershocks generally improve the predictive power in particular for the purely statistical models in space and time.

Description: The most commonly cited definition of industrial symbiosis (IS), by Chertow (2000) , has served well to foster discussion and research for more than a decade. The definition reflected the state of research and practice at the time; as both have advanced, some terms have been interpreted in substantially different ways. In this article we analyze those generally used terms for their connection to the ecological metaphor that is the root of industrial ecology, and their varied interpretations in IS research and practice over time. We then propose an updated definition intended to communicate the essence of IS as a tool for innovative green growth: IS engages diverse organizations in a network to foster eco-innovation and long-term culture change. Creating and sharing knowledge through the network yields mutually profitable transactions for novel sourcing of required inputs and value-added destinations for non-product outputs, as well as improved business and technical processes. We posit that, although geographic proximity is often associated with IS, it is neither necessary nor sufficient—nor is a singular focus on physical resource exchange.

Description: In this study we map the distribution of the b-value of the Gutenberg-Richter law—as well as complementary seismicity parameters—along the fault responsible for the 2009 MW 6.1 L'Aquila earthquake. We perform the calculations for two independent aftershock sub-catalogs, before and after a stable magnitude of completeness is reached. We find a substantial spatial variability of the b-values, which range from 0.6 to 1.3 over the fault plane. The comparison between the spatial distribution of the b-values and the main-shock slip pattern shows that the largest slip occurs in normal-to-high b-values portion of the fault plane, while low b-value is observed close to the main-shock nucleation. No substantial differences are found in the b-value computed before and after the main-shock struck in the small region of the fault plane populated by foreshocks.

Description: Questions Could mountain pine ( Pinus mugo Turra subsp. mugo ) located above the timberline and at the southern limit of its potential geographic distribution be a promising species to monitor climatic change in specific environments such as the Mediterranean mountains? Does mountain pine krummholz upward expansion result from current climate change? Has the relationship between climate and tree ring growth of mountain pine changed? To what extent does climatic variability affect tree ring growth? Could mountain pine upward expansion contribute to loss of biodiversity in the undisturbed tree line ecotone on the Majella massif? Location Majella National Park, Apennines, Italy. Methods Dendroclimatological analysis was performed to examine the relationship between tree rings of mountain pine and climatic parameters at the tree line. Climate–growth relationships were analysed using correlation function (CF) analysis and moving CF (MCF). Results In the Majella massif, climate variables affected mountain pine tree growth at the tree line ecotone. Significant correlations were found with spring temperatures and summer precipitation. Essentially, three months played a key role in mountain pine growth: April and May of the current year and October of the previous year. MCF showed that mountain pine is a sensitive species, in terms of tree ring growth. Conclusions Growing above the limit of tree vegetation, mountain pine proved to be a promising species for monitoring climate- and land use-driven influences over tree ring growth at high elevations. Our results show that mountain pine is particularly sensitive to climate at the beginning and at the end of the growing season. This study contributed to better understand the vegetation dynamics at the treeline on Mediterranean mountains. The response of the krummholz species Pinus mugo Turra subsp. mugo to climate in Apennines (Central Italy) and the temporal variation of tree ring sensitivity to climate were used for monitoring climate-driven influences over ring width growth at high elevation.

Description: [1]  Soil-gas measurements of different gas species with different geochemical behaviours were performed in the area of the Pecore Plain, a 200m x 300m sized, fault-bounded extensional basin located in the northern Mt. Marzano massif, in the axial belt of the southern Apennine chain. The Pecore Plain area was affected by coseismic surface faulting during the Ms=6.9, 1980 Irpinia earthquake, the strongest and most destructive seismic event of the last 30 years in southern Italy. The collected data and their geostatistical analysis provide new insights into the control exerted by active fault segments on deep-seated gas migration towards the surface. The results define anomalies that are aligned with the NW-SE trending coseismic rupture of the 1980 earthquake along the western border of the plain, as well as along the southern border of the plain where a hidden, E-W striking fault is inferred. Geospatial analysis highlights an anisotropic spatial behaviour of 222 Rn along the main NW-SE trend and of CO 2 along the E-W trend. This feature suggests a correlation between the shape and orientation of the anomalies and the barrier/conduit behaviour of fault zones in the area. Furthermore, our results show that gas migration through brittle deformation zones occurs by advective processes, as suggested by the relatively high migration rate needed to obtain anomalies of short-lived 222 Rn in the soil pores.

Description: Introduction In the non-thalassemic population hypothyroidism has been associated with an increased risk of cardiac disease while the link thyroid-heart disease has been little explored in thalassemia major (TM). This retrospective cohort study aimed to systematically evaluate in a large historical cohort of TM in the cardiovascular magnetic resonance (CMR) era whether hypothyroidism was associated with a higher risk of heart complications (heart failure, arrhythmias and pulmonary hypertension). Methods From a cohort of 957 TM patients who underwent CMR for myocardial iron overload (MIO) assessment, quantification of biventricular function and detection of myocardial fibrosis within the MIOT network (Myocardial Iron Overload in Thalassemia), we identified 115 (12%) hypothyroid patients. Each hypothyroid patient was matched by sex and age (at the time of the CMR) with two non-hypothyroid patients, creating 115 triples. A cardiac event was considered valid if diagnosed at an age older than the hypothyroidism’s onset age for the hypothyroid patient in the belonging triple. Results Hypothyroid and non-hypothyroid patients had comparable MIO, but hypothyroid patients showed significantly lower biventricular stroke volume index, ejection fraction and left ventricular cardiac index. Accordingly, the prevalence of overall heart dysfunction (LV, RV or both) was higher in hypothyroid patients (43.5% vs 33.5%, P=0.0314). Hypothyroid patients had a significant higher frequency of heart failure (19.1% vs 9.1%, P=0.003) and arrhythmias (11.3% vs 4.3%; P=0.003). Figure1 shows odds ratios (OR) estimating the relationship between hypothyroidism and cardiac involvement. Hypothyroid patients had a significant higher risk of heart dysfunction, heart failure and arrhythmias, also adjusting for the endocrine co-morbidity. Conclusions Hypothyroidism seems to increase the risk for heart failure, arrhythmias and heart dysfunction in TM patients. Our data confirm the link thyroid-heart disease also in TM patients and they stress the need to prevent hypothyroidism in this population. Disclosures: No relevant conflicts of interest to declare.