Are the winters 2010 and 2012 archetypes exhibiting extreme opposite behavior of the North Atlantic jet stream?

The atmospheric circulation over the North Atlantic-European sector experienced exceptional but highly contrasting conditions in the recent 2010 and 2012 winters (November-March; with the year dated by the relevant January). Evidence is given for the remarkably different locations of the eddy-driven westerly jet over the North Atlantic. In the 2010 winter the maximum of the jet stream was systematically between 30ºN and 40ºN (in the ‘south jet regime’), while in the 2012 winter it was predominantly located around 55ºN (north jet regime). These jet features underline the occurrence of either weak flow (2010) or strong and persistent ridges throughout the troposphere (2012). This is confirmed by the very different occurrence of blocking systems over the North Atlantic, associated with episodes of strong cyclonic (anticyclonic) Rossby wave breaking in 2010 (2012) winters. These dynamical features underlie strong precipitation and temperature anomalies over parts of Europe, with detrimental impacts on many socioeconomic sectors. Despite the highly contrasting atmospheric states, mid and high-latitude boundary conditions do not reveal strong differences in these two winters. The two winters were associated with opposite ENSO phases, but there is no causal evidence of a remote forcing from the Pacific sea surface temperatures. Finally, the exceptionality of the two winters is demonstrated in relation to the last 140 years. It is suggested that these winters may be seen as archetypes of North Atlantic jet variability under current climate conditions

Deformation-induced microstructural banding in TRIP steels

Microstructure inhomogeneities can strongly influence the mechanical properties of advanced high-strength steels in a detrimental manner. This study of a transformation-induced plasticity (TRIP) steel investigates the effect of pre-existing contiguous grain boundary networks (CGBNs) of hard second-phases and shows how these develop into bands during tensile testing using in situ observations in conjunction with digital image correlation (DIC). The bands form by the lateral contraction of the soft ferrite matrix, which rotates and displaces the CGBNs of second-phases and the individual features within them to become aligned with the loading direction. The more extensive pre-existing CGBNs that were before the deformation already aligned with the loading direction are the most critical microstructural feature for damage initiation and propagation. They induce micro-void formation between the hard second-phases along them, which coalesce and develop into long macroscopic fissures. The hard phases, retained austenite and martensite, were not differentiated as it was found that the individual phases do not play a role in the formation of these bands. It is suggested that minimizing the presence of CGBNs of hard second-phases in the initial microstructure will increase the formability

Potent Inhibition of HIV-1 Replication by a Tat Mutant

Herein we describe a mutant of the two-exon HIV-1 Tat protein, termed Nullbasic, that potently inhibits multiple steps of the HIV-1 replication cycle. Nullbasic was created by replacing the entire arginine-rich basic domain of wild type Tat with glycine/alanine residues. Like similarly mutated one-exon Tat mutants, Nullbasic exhibited transdominant negative effects on Tat-dependent transactivation. However, unlike previously reported mutants, we discovered that Nullbasic also strongly suppressed the expression of unspliced and singly-spliced viral mRNA, an activity likely caused by redistribution and thus functional inhibition of HIV-1 Rev. Furthermore, HIV-1 virion particles produced by cells expressing Nullbasic had severely reduced infectivity, a defect attributable to a reduced ability of the virions to undergo reverse transcription. Combination of these inhibitory effects on transactivation, Rev-dependent mRNA transport and reverse transcription meant that permissive cells constitutively expressing Nullbasic were highly resistant to a spreading infection by HIV-1. Nullbasic and its activities thus provide potential insights into the development of potent antiviral therapeutics that target multiple stages of HIV-1 infection

The Interdomain Region of Dengue NS5 Protein That Binds to the Viral Helicase NS3 Contains Independently Functional Importin beta 1 and Importin alpha /beta -Recognized Nuclear Localization Signals

Dengue virus NS5 protein is a multifunctional RNA-dependent RNA polymerase that is essential for virus replication. We have shown previously that the 37- amino acid interdomain spacer sequence (residues 369X2KKX14KKKX11RKX3405) of Dengue2 NS5 contains a functional nuclear localization signal (NLS). In this study, beta -galactosidase fusion proteins carrying point mutations of the positively charged residues or truncations of the interdomain linker region (residues 369-389 or residues 386-405) were analyzed for nuclear import and importin binding activities to show that the N-terminal part of the linker region (residues 369-389, a/bNLS) is critical for nuclear localization and is recognized with high affinity by the conventional NLS-binding importin alpha /beta heterodimeric nuclear import receptor. We also show that the importin beta -binding site (residues 320-368, bNLS) adjacent to the a/bNLS, previously identified by yeast two-hybrid analysis, is functional as an NLS, recognized with high affinity by importin beta , and able to target beta -galactosidase to the nucleus. Intriguingly, the bNLS is highly conserved among Dengue and related flaviviruses, implying a general role for the region and importin beta in the infectious cycle

Association of Tat with Promoters of PTEN and PP2A Subunits Is Key to Transcriptional Activation of Apoptotic Pathways in HIV-Infected CD4+ T Cells

Apoptosis in HIV-1-infected CD4+ primary T cells is triggered by the alteration of the PI3K and p53 pathways, which converge on the FOXO3a transcriptional activator. Tat alone can cause activation of FOXO3a and of its proapoptotic target genes. To understand how Tat affects this pathway, we carried out ChIP-Chip experiments with Tat. Tat associates with the promoters of PTEN and two PP2A subunit genes, but not with the FOXO3a promoter. PTEN and PP2A encode phosphatases, whose levels and activity are increased when Tat is expressed. They counteract phosphorylation of Akt1 and FOXO3a, and so activate transcriptional activity of FOXO3a. FOXO3a promotes increased transcription of Egr-1, which can further stimulate the transcription of PTEN, thereby reinforcing the pathway that leads to FOXO3a transcriptional activation. RNAi experiments support the role of PTEN and PP2A in the initiation of the Tat-mediated cascade, which is critical to apoptosis. The increased accumulation of PTEN and PP2A subunit mRNAs during Tat expression is more likely to be the result of increased transcription initiation and not relief of promoter-proximal pausing of RNAPII. The Tat-PTEN and -PP2A promoter interactions provide a mechanistic explanation of Tat-mediated apoptosis in CD4+ T cells

HIV-1 Tat and AIDS-associated cancer: targeting the cellular anti-cancer barrier?

The acquired immunodeficiency syndrome (AIDS) is accompanied by a significant increase in the incidence of neoplasms. Several causative agents have been proposed for this phenomenon. These include immunodeficiency and oncogenic DNA viruses and the HIV-1 protein Tat. Cancer in general is closely linked to genomic instability and DNA repair mechanisms. The latter maintains genomic stability and serves as a cellular anti-cancer barrier. Defects in DNA repair pathway are associated with carcinogenesis

Variability in storm climate along the Gulf of Cadiz: the role of large scale atmospheric forcing and implications to coastal hazards

In the context of increased coastal hazards due to variability in storminess patterns, the danger of coastal damages and/or morphological changes is related to the sum of sea level conditions, storm surge, maximum wave height and run up values. In order to better understand the physical processes that cause the variability of the above parameters a 44 years reanalysis record (HIPOCAS) was used. The HIPOCAS time-series was validated with real wave and sea-level data using linear and vector correlation methods. In the present work changes in the magnitude, duration, frequency and approach direction of the Atlantic storms over the Gulf of Cadiz (SW Iberian Peninsula) were identified by computing various storm characteristics such as maximum wave height, total energy per storm wave direction and storm duration. The obtained time-series were compared with large-scale atmospheric indices such as the North Atlantic Oscillation (NAO) and the East Atlantic pattern. The results show a good correlation between negative NAO values and increased storminess over the entire Gulf of Cadiz. Furthermore, negative NAO values were correlated with high residual sea level values. Finally, a joint probability analysis of storm and sea level analysis resulted in increased probabilities of the two events happening at the same time indicating higher vulnerability of the coast and increased coastal risks. The above results were compared with coastal inundation events that took place over the last winter seasons in the province of Cadiz.info:eu-repo/semantics/publishedVersio

Successful Salvage Resection of Locoregional Colon Cancer Recurrence. Report of Four Cases

Locoregional colorectal cancer recurrence after curative resection remains a clinical problem despite improvements in surgical techniques. A surgical approach is usually preferred, although controversies exist. Retrospective studies have identified risk factors that may predict successful outcomes after reoperation. In the current manuscript, the experience of our tertiary oncology center involving cases with complicated locoregional recurrences is reported. Four such patients were identified, age 55-69 years old, who were treated with an aggressive surgical intervention in the setting of multimodality treatment including postoperative chemotherapy and radiation. Despite the presence of risk factors, such as involvement of adjacent structures, an excellent disease-free survival was achieved. We, therefore, propose that aggressive surgical approach supported by modern chemotherapy and occasionally radiotherapy for the treatment of colorectal cancer locoregional relapses should be considered in the setting of a multidisciplinary oncologic evaluation