Wave extreme characterization using self-organizing maps

The self-organizing map (SOM) technique is considered and extended to assess the extremes of a multivariate sea wave climate at a site. The main purpose is to obtain a more complete representation of the sea states, including the most severe states that otherwise would be missed by a SOM. Indeed, it is commonly recognized, and herein confirmed, that a SOM is a good regressor of a sample if the frequency of events is high (e.g., for low/moderate sea states), while a SOM fails if the frequency is low (e.g., for the most severe sea states). Therefore, we have considered a trivariate wave climate (composed by significant wave height, mean wave period and mean wave direction) collected continuously at the Acqua Alta oceanographic tower (northern Adriatic Sea, Italy) during the period 1979–2008. Three different strategies derived by SOM have been tested in order to capture the most extreme events. The first contemplates a pre-processing of the input data set aimed at reducing redundancies; the second, based on the post-processing of SOM outputs, consists in a two-step SOM where the first step is applied to the original data set, and the second step is applied on the events exceeding a given threshold. A complete graphical representation of the outcomes of a two-step SOM is proposed. Results suggest that the post-processing strategy is more effective than the pre-processing one in order to represent the wave climate extremes. An application of the proposed two-step approach is also provided, showing that a proper representation of the extreme wave climate leads to enhanced quantification of, for instance, the alongshore component of the wave energy flux in shallow water. Finally, the third strategy focuses on the peaks of the storms

Operativni sustav za prognoziranje hipoksije u sjevernom Jadranu

The northern Adriatic Sea (NA), the northernmost region of the Mediterranean Sea, is affected by strong anthropogenic pressure (e.g., tourism, fisheries, maritime traffic, discharge from agriculture and industry), superimposed to a large river runoff. The consequent pressure exerted on the NA ecosystem either triggers or worsens massive mucilage insurgence, harmful algal blooms, eutrophication and even anoxic/hypoxic events. This work focuses on the anoxic/hypoxic events. During the summer-autumn period, the NA is often exposed to these events, which can be categorised as either coastal (relatively frequent south of the Po River delta during the summer) and offshore (rare, affecting wider areas). In order to improve our knowledge about these processes and to meet the needs of local governments and decision makers, an operational system for monitoring and forecasting anoxic and hypoxic events has been set up in the framework of the EU LIFE "EMMA" project. The system is composed of a meteo-oceanographic buoy; a numerical prediction system based on the Regional Ocean Modelling System (ROMS), including a Fasham-type module for biogeochemical fluxes; and periodic oceanographic surveys. Every day since June 2007, the system provides 3-hourly forecasts of marine currents, thermohaline and biogeochemical fields for the incoming three days. The system has demonstrated its ability to produce accurate temperature forecasts and relatively good salinity and dissolved oxygen forecasts. The Root Mean Square Error of the dissolved oxygen forecast was largely due to the mean bias. The system is currently being improved to include a better representation of benthic layer biogeochemical processes and several adjustments of the model. While developing model improvements, dissolved oxygen forecasts were improved with the removal of the 10-day mean bias.Sjeverni Jadran (NA), najsjeverniji dio Sredozemnog mora, pod utjecajem je jakog antropogenog djelovanja (poput turizma, ribarenja, morskog prometa, istjecanje onečišćujućih tvari u poljoprivredi i industriji) te dodatno, velikog dotoka rijeka. Posljedično, djelovanje na NA ekosustav potiče ili pojačava uzdizanje sluzavih nakupina, štetno cvjetanje algi, eutrofikaciju pa čak i događaje anoksije/hipoksije. Ovaj se rad fokusira na anoksiju/hipoksiju. Tijekom ljetno-jesenskog razdoblja, NA je često izložen ovim doga|ajima, koji se mogu kategorizirati kao obalni (relativno učestali južno od delte rijeke Po ljeti) ili udaljeni od obale (rijetki, zahvaćajući šira područja). Kako bi poboljšali poznavanje tih procesa te zbog potreba lokalne uprave, uspostavljen je operativni sustav za praćenje i prognoziranje anoksije i hipoksije u okviru EU LIFE "EMMA" projekta. Sustav se sastoji od meteorološko-oceanografske plutače; sustava za numeričku prognozu, koji se temelji na regionalnom oceanografskom modelu (ROMS), uključujući modul Fasham-tipa za biogeokemijske tokove; i periodičnim oceanografskim istraživanjima. Svakog dana, počev od lipnja 2007, sustav omogućava 3-satne prognoze morskih struja te termohalina i biogeokemijska polja za sljedeća tri dana. Sustav se pokazao sposobnim za davanje točnih prognoza temperature i relativno dobrih prognoza saliniteta i otopljenog kisika. Korijen srednje kvadratne pogreške prognoziranog otopljenog kisika postojao je uglavnom zbog srednje pristranosti (biasa). Sustav je trenutno poboljšan tako da uključuje bolji prikaz biogeokemijskih procesa u području sloja bentosa i nekoliko prilagodba modela. Tijekom poboljšavanja modela, uklanjanjem 10-dnevne srednje pristranosti (biasa) poboljšane su prognoze otopljenog kisika

C2C12 murine myoblasts as a model of skeletal muscle development: morpho-functional characterization

In this study, the differentiation of C2C12 cells, a primary line of murine myoblasts, was investigated by a multiple technical approach. Undifferentiated cells, and those at intermediate and final differentiation times, were studied at the reverted microscope, by conventional and confocal immunofluorescence, and by transmission and scanning electron microscopy. The general monolayer architecture changed during differentiation from fusiform or star-shaped cells to elongated confluent cells, finally originating long, multinucleated myotubes. Sarcomeric actin and myosin are present also in undifferentiated myoblasts, but progressively acquire a structured pattern up to the appearance of sarcomeres and myofibrils at about 5 days after differentiation induction. Myotubes show a particular positivity for actin and myosin, and M-cadherin, an adhesion molecule characteristic, as known, of satellite cells, also seems to be involved in their assembling. Rare apoptotic patterns, as evidenced by the TUNEL technique, appear during myoblast maturation

AMP-dependent kinase/mammalian target of rapamycin complex 1 signaling in T-cell acute lymphoblastic leukemia: therapeutic implications.

The mammalian target of rapamycin (mTOR) serine/threonine kinase is the catalytic subunit of two multi-protein complexes, referred to as mTORC1 and mTORC2. Signaling downstream of mTORC1 has a critical role in leukemic cell biology by controlling mRNA translation of genes involved in both cell survival and proliferation. mTORC1 activity can be downmodulated by upregulating the liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) pathway. Here, we have explored the therapeutic potential of the anti-diabetic drug, metformin (an LKB1/AMPK activator), against both T-cell acute lymphoblastic leukemia (T-ALL) cell lines and primary samples from T-ALL patients displaying mTORC1 activation. Metformin affected T-ALL cell viability by inducing autophagy and apoptosis. However, it was much less toxic against proliferating CD4þ T-lymphocytes from healthy donors. Western blot analysis demonstrated dephosphorylation of mTORC1 downstream targets. Unlike rapamycin, we found a marked inhibition of mRNA translation in T-ALL cells treated with metformin. Remarkably, metformin targeted the side population of T-ALL cell lines as well as a putative leukemia-initiating cell subpopulation (CD34þ/CD7/CD4) in patient samples. In conclusion, metformin displayed a remarkable anti-leukemic activity, which emphasizes future development of LKB1/AMPK activators as clinical candidates for therapy in T-ALL. Leukemia (2012) 26, 91–100; doi:10.1038/leu.2011.269; published online 4 October 201

How physical exercise changes rat myotendinous junctions : an ultrastructural study

Myotendinous junctions can be easily injured by overloading or trauma, and exercise training may be a way of increasing their resistance to mechanical stress. To this end, we examined herein the morphological changes induced by moderate exercise training in the myotendinous junctions of extensor digitorum longus and gastrocnemius muscles in rats. Twelve Sprague-Dawley rats were used in this investigation. Six of them were trained to run on a treadmill for 1 h/day, 3 days/week over 10 weeks in order for them to achieve a running rate of 25 m/min at the end of the training period. Six age-matched sedentary rats were used as controls. The rats were sacrificed 24 h after the final training session, and the extensor digitorum longum (EDL) and the gastrocnemium were excised; the myotendinous junctions (MTJ) were then prepared and observed with electron microscopy. Digitation branching was evaluated by counting the bifurcations in the MTJ protrusions. Our observations indicate that exercise does indeed induce changes in MTJ morphology. In both muscles the number of bifurcated interdigitations increased significantly, as well as, in gastrocnemius, the branching of the finger-like processes. It was demonstrated that the MTJ is able to adapt to an increase in tensile force by enlarging the muscle-tendon contact area and, consequently, mechanical resistance

Partial persistence of exercise-induced myocardial angiogenesis following 4-week detraining in the rat

Enhanced angiogenesis, or capillary growth, has a prominent role among the various beneficial effects of exercise training on the myocardium. The aim of the present study is to assess if training-induced increases in capillarity and vascularization persist after 4 weeks of detraining. Adult male rats were trained to run on a treadmill for 10 weeks at approximately 60% VO(2max), which did not induce cardiac hypertrophy, but increased (P < 0.05) the soleus/body weight ratio, left ventricle capillarity and von Willebrand-positive cell density (n = 6). In another group of animals (n = 6) subjected to training followed by 4-week detraining, the soleus/body weight ratio returned to normal, with only partial reversal of left ventricle capillarity and von Willebrand-positive cell density. Markers of angiogenesis (VEGF, KDR/VEGF-R2 and HIF-1alpha mRNA, studied by real-time RT-PCR) were upregulated at the end of training, and returned to baseline value after detraining. Electron microscopy highlighted some morphological features in trained hearts (endothelial cell sprouting and bridges and pericyte detachment), suggestive of endothelial cell proliferation and capillary growth that were absent in untrained and detrained hearts. We conclude that the training-induced increase in cardiac capillarity and vascularization are retained for some time upon cessation of the training program even in the absence of angiogenic stimuli

Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction – A model for cross-modulation

<p>Abstract</p> <p>Background</p> <p>A feature of epithelial to mesenchymal transition (EMT) relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC.</p> <p>Methods</p> <p>PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome.</p> <p>Results</p> <p>When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4). Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse correlation with lower expression values being predictive of increased risk.</p> <p>Conclusion</p> <p>ST in combination with EGF directed a greater EMT via actin depolymerisation and focal contact size reduction, resulting in a loosening of cell-ECM attachment along with Snail1-Zeb1/δEF1 induction. This appeared fundamentally different to the EGF-induced EMT, highlighting the multiple pathways which can regulate EMT. Our findings add support for a functional role for Snail1 in invasive breast cancer.</p

CALYPSO 2019 Cruise Report: field campaign in the Mediterranean

This cruise aimed to identify transport pathways from the surface into the interior ocean during the late winter in the Alborán sea between the Strait of Gibraltar (5°40’W) and the prime meridian. Theory and previous observations indicated that these pathways likely originated at strong fronts, such as the one that separates salty Mediterranean water and the fresher water in owing from the Atlantic. Our goal was to map such pathways and quantify their transport. Since the outcropping isopycnals at the front extend to the deepest depths during the late winter, we planned the cruise at the end of the Spring, prior to the onset of thermal stratification of the surface mixed layer.Funding was provided by the Office of Naval Research under Contract No. N000141613130