Is flow velocity important in tsunami empirical fragility modeling?

The influence of flow velocity on structural damage induced by tsunami inundation is investigated to improve empirical fragility models considering flow velocity as explanatory hazard variable in addition to inundation depth. The analysis is based on extensive tsunami damage data for the 2011 Tohoku earthquake collected by the Ministry of Land, Infrastructure, and Transportation of the Japanese Government. Multivariate tsunami fragility curves are developed through multinomial logistic regression of un-binned data. This approach facilitates the flexible development of various nested models considering inundation depth alone or inundation depth and velocity altogether. Statistical diagnostic metrics, such as the Bayesian Information Criterion, the Akaike Information Criterion, and the residual deviance, are used to determine which model improves the predictability of tsunami damage. The significance and importance of including flow velocity in the vulnerability models are assessed quantitatively by examining the influence of different spatial resolutions in elevation model and different source models. Then, the effects of coastal topography have been investigated. Numerical results show that flow velocity generally improves the fragility models, particularly for severer structural damage states, and that it is important for sites along the coast where the inundation depth is not extremely high. Coarse digital elevation model and inaccurate source models have influence on the calculated values of flow velocity and thus they affect the accuracy of fragility modeling. Finally, two different fragility models are calibrated for plain-type and ria-type coasts by reflecting differences in hydrodynamic behavior and recorded damage on the structures

TYK2-induced phosphorylation of Y640 suppresses STAT3 transcriptional activity

STAT3 is a pleiotropic transcription factor involved in homeostatic and host defense processes in the human body. It is activated by numerous cytokines and growth factors and generates a series of cellular effects. Of the STAT-mediated signal transduction pathways, STAT3 transcriptional control is best understood. Jak kinase dependent activation of STAT3 relies on Y705 phosphorylation triggering a conformational switch that is stabilized by intermolecular interactions between SH2 domains and the pY705 motif. We here show that a second tyrosine phosphorylation within the SH2 domain at position Y640, induced by Tyk2, negatively controls STAT3 activity. The Y640F mutation leads to stabilization of activated STAT3 homodimers, accelerated nuclear translocation and superior transcriptional activity following IL-6 and LIF stimulation. Moreover, it unlocks type I IFN-dependent STAT3 signalling in cells that are normally refractory to STAT3 transcriptional activation

Association between a genetic variant of type-1 cannabinoid receptor and inflammatory neurodegeneration in multiple sclerosis

Genetic ablation of type-1 cannabinoid receptors (CB1Rs) exacerbates the neurodegenerative damage of experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS). To address the role on CB1Rs in the pathophysiology of human MS, we first investigated the impact of AAT trinucleotide short tandem repeat polymorphism of CNR1 gene on CB1R cell expression, and secondly on the inflammatory neurodegeneration process responsible for irreversible disability in MS patients. We found that MS patients with long AAT repeats within the CNR1 gene (≥12 in both alleles) had more pronounced neuronal degeneration in response to inflammatory white matter damage both in the optic nerve and in the cortex. Optical Coherence Tomography (OCT), in fact, showed more severe alterations of the retinal nerve fiber layer (RNFL) thickness and of the macular volume (MV) after an episode of optic neuritis in MS patients carrying the long AAT genotype of CNR1. MS patients with long AAT repeats also had magnetic resonance imaging (MRI) evidence of increased gray matter damage in response to inflammatory lesions of the white matter, especially in areas with a major role in cognition. In parallel, visual abilities evaluated at the low contrast acuity test, and cognitive performances were negatively influenced by the long AAT CNR1 genotype in our sample of MS patients. Our results demonstrate the biological relevance of the (AAT)n CNR1 repeats in the inflammatory neurodegenerative damage of MS

Bioactive Compounds and Antioxidant Properties of Wild Rocket (Diplotaxis Tenuifolia L.) Grown under Different Plastic Films and with Different UV-B Radiation Postharvest Treatments

: Rocket species are rich in nutrients with well-known bioactive activity, but their content depends on several factors, such as plant-UV radiation interaction. In this work, we measured the production of nutritional elements in wild rocket (Diplotaxis tenuifolia L.) leaves as a function of exposure to UV-B radiation by adopting a combined approach. The wild rocket plants were grown under three greenhouse cover films (A, B, and C) having different transmittivity to UV-B and the fresh-cut leaves were exposed to UV-B in postharvest for 45, 150, 330, and 660 s. The content of chlorophyll, carotenoids, phenolic compounds, ascorbic acid, and the antioxidant activity were determined. Chlorophyll, carotenoids, and total phenolic content were significantly increased by the combination of Film C and treatment with UV-B for 45 s. The predominant phenolic compounds were kaempferol, isorhamnetin, and quercetin. Film C also elicited an increase in ascorbic acid (the most abundant antioxidant compound in the range 374-1199 per 100 g of dry matter) and antioxidant activity. These findings highlighted an increase in bioactive compound content in the wild rocket when it was cultivated under Film C (diffused light film with a tailored UV-B transmission dose) and treated with UV-B radiation for 45 s postharvest, corresponding to an energy dose of 0.2 KJ m-2

The FHIT Gene, Spanning the Chromosome 3p14.2 Fragile Site and Renal Carcinoma–Associated t(3;8) Breakpoint, Is Abnormal in Digestive Tract Cancers

AbstractA 200–300 kb region of chromosome 3p14.2, including the fragile site locus FRA3B, is homozygously deleted in multiple tumor-derived cell lines. Exon amplification from cosmids covering this deleted region allowed identification of the human FHIT gene, a member of the histidine triad gene family, which encodes a protein with 69% similarity to an S. pombe enzyme, diadenosine 5′, 5′′′ P1, P4-tetraphosphate asymmetrical hydrolase. The FHIT locus is composed of ten exons distributed over at least 500 kb, with three 5′ untranslated exons centromeric to the renal carcinoma–associated 3p14.2 breakpoint, the remaining exons telomeric to this translocation breakpoint, and exon 5 within the homozygously deleted fragile region. Aberrant transcripts of the FHIT locus were found in ∼50% of esophageal, stomach, and colon carcinomas

QuickRank: a C++ Suite of Learning to Rank Algorithms

Ranking is a central task of many Information Retrieval (IR) problems, particularly challenging in the case of large-scale Web collections where it involves effectiveness requirements and effciency constraints that are not common to other ranking-based applications. This paper describes QuickRank, a C++ suite of effcient and effective Learning to Rank (LtR) algorithms that allows high-quality ranking functions to be devised from possibly huge training datasets. QuickRank is a project with a double goal: i) answering industrial need of Tiscali S.p.A. for a exible and scalable LtR solution for learning ranking models from huge training datasets; ii) providing the IR research community with a exible, extensible and effcient LtR framework to design LtR solutions and fairly compare the performance of different algorithms and ranking models. This paper presents our choices in designing QuickRank and report some preliminary use experiences.Ranking is a central task of many Information Retrieval (IR) problems, particularly challenging in the case of large-scale Web collections where it involves eectiveness requirements and eciency constraints that are not common to other ranking-based applications. This paper describes QuickRank, a C++ suite of ecient and eective Learning to Rank (LtR) algorithms that allows high-quality ranking functions to be devised from possibly huge training datasets. QuickRank is a project with a double goal: i) answering industrial need of Tiscali S.p.A. for a exible and scalable LtR solution for learning ranking models from huge training datasets; ii) providing the IR research community with a exible, extensible and ecient LtR framework to design LtR solutions and fairly compare the performance of dierent algorithms and ranking models. This paper presents our choices in designing QuickRank and report some preliminary use experiences

Expansion and subfunctionalisation of flavonoid 3',5'-hydroxylases in the grapevine lineage

<p>Abstract</p> <p>Background</p> <p>Flavonoid 3',5'-hydroxylases (F3'5'Hs) and flavonoid 3'-hydroxylases (F3'Hs) competitively control the synthesis of delphinidin and cyanidin, the precursors of blue and red anthocyanins. In most plants, <it>F3'5'H </it>genes are present in low-copy number, but in grapevine they are highly redundant.</p> <p>Results</p> <p>The first increase in <it>F3'5'H </it>copy number occurred in the progenitor of the eudicot clade at the time of the γ triplication. Further proliferation of <it>F3'5'H</it>s has occurred in one of the paleologous loci after the separation of Vitaceae from other eurosids, giving rise to 15 paralogues within 650 kb. Twelve reside in 9 tandem blocks of ~35-55 kb that share 91-99% identity. The second paleologous <it>F3'5'H </it>has been maintained as an orphan gene in grapevines, and lacks orthologues in other plants. Duplicate <it>F3'5'H</it>s have spatially and temporally partitioned expression profiles in grapevine. The orphan <it>F3'5'H </it>copy is highly expressed in vegetative organs. More recent duplicate <it>F3'5'H</it>s are predominately expressed in berry skins. They differ only slightly in the coding region, but are distinguished in the structure of the promoter. Differences in <it>cis</it>-regulatory sequences of promoter regions are paralleled by temporal specialisation of gene transcription during fruit ripening. Variation in anthocyanin profiles consistently reflects changes in the <it>F3'5'H </it>mRNA pool across different cultivars. More <it>F3'5'H </it>copies are expressed at high levels in grapevine varieties with 93-94% of 3'5'-OH anthocyanins. In grapevines depleted in 3'5'-OH anthocyanins (15-45%), fewer <it>F3'5'H </it>copies are transcribed, and at lower levels. Conversely, only two copies of the gene encoding the competing F3'H enzyme are present in the grape genome; one copy is expressed in both vegetative and reproductive organs at comparable levels among cultivars, while the other is transcriptionally silent.</p> <p>Conclusions</p> <p>These results suggest that expansion and subfunctionalisation of <it>F3'5'H</it>s have increased the complexity and diversification of the fruit colour phenotype among red grape varieties.</p