Idealised simulations of cyclones with robust symmetrically-unstable sting jets

Idealised simulations of Shapiro-Keyser cyclones developing a sting jet (SJ) are presented. Thanks to an improved and accurate implementation of thermal wind balance in the initial state, it has been possible to use more realistic environments than in previous idealised studies. As a consequence, this study provides further insight in SJ evolution and dynamics and explores SJ robustness to different environmental conditions, assessed via a wide range of sensitivity experiments. The control simulation contains a cyclone that fits the Shapiro-Keyser conceptual model and develops a SJ whose dynamics are associated with the evolution of mesoscale instabilities along the airstream, including symmetric instability (SI). The SJ undergoes a strong descent while leaving the cloud-head banded tip and markedly accelerating towards the frontal-fracture region, revealed as an area of buckling of the already-sloped moist isentropes. Dry instabilities, generated by vorticity tilting via slantwise frontal motions in the cloud head, exist in similar proportions to moist instabilities at the start of the SJ descent and are then released along the SJ. The observed evolution supports the role of SI in the airstream’s dynamics proposed in a conceptual model outlined in a previous study. Sensitivity experiments illustrate that the SJ is a robust feature of intense Shapiro-Keyser cyclones, highlighting a range of different environmental conditions in which SI contributes to the evolution of this airstream, conditional on the model having adequate resolution. The results reveal that several environmental factors can modulate the strength of the SJ. However, a positive relationship between the strength of the SJ, both in terms of peak speed and amount of descent, and the amount of instability occurring along it can still be identified. In summary, the idealised simulations presented in this study show the robustness of SJ occurrence in intense Shapiro-Keyser cyclones and support and clarify the role of dry instabilities in SJ dynamics

Behavioral disturbances in dementia and beyond: Time for a new conceptual frame?

Alzheimer\u2019s disease and vascular dementia are estimated to be the most common causes of dementia, although mixed dementia could represent the most prevalent form of dementia in older adults aged more than 80 years. Behavioral disturbances are common in the natural history of dementia. However, so far, there is a paucity of studies that investigated the causal association between behavioral psychological symptoms of dementia and dementia sub-types, due to the high heterogeneity of methodology, study design and type of clinical assessment. To understand the scant evidence on such a relevant clinical issue, it could be hypothesized that a new shifting paradigm could result in a better identification of the relationship between behavioral disturbances and dementia. This narrative review provides an update of evidence on the behavioral patterns associated with different dementia sub-types and offers a potential future perspective as common ground for the development of new translational studies in the field of behavioral disturbances in dementia and the appropriateness of psychoactive treatments

The Down syndrome critical region protein TTC3 inhibits neuronal differentiation via RhoA and Citron kinase.

The Down syndrome critical region (DSCR) on Chromosome 21 contains many genes whose duplication may lead to the major phenotypic features of Down syndrome and especially the associated mental retardation. However, the functions of DSCR genes are mostly unknown and their possible involvement in key brain developmental events still largely unexplored. In this report we show that the protein TTC3, encoded by one of the main DSCR candidate genes, physically interacts with Citron kinase (CIT-K) and Citron N (CIT-N), two effectors of the RhoA small GTPase that have previously been involved in neuronal proliferation and differentiation. More importantly, we found that TTC3 levels can strongly affect the NGF-induced differentiation of PC12 cells, by a CIT-K-dependent mechanism. Indeed, TTC3 overexpression leads to strong inhibition of neurite extension, which can be reverted by CIT-K RNAi. Conversely, TTC3 knockdown stimulates neurite extension in the same cells. Finally, we find that Rho, but not Rho kinase, is required for TTC3 differentiation-inhibiting activity. Our results suggest that the TTC3–RhoA–CIT-K pathway could be a crucial determinant of in vivo neuronal development, whose hyperactivity may result in detrimental effects on the normal differentiation program

Analisi dei costi dell\u2019assistenza domiciliare integrata : l\u2019esperienza della Regione Calabria

The need to contain healthcare expenditure, looking at quality of assistance as well, has lead recently to the implementation of new assistance paradigms. Home hospitalization is intended to improve quality of assistance, because it ensure the patients to remain in their own environment, assisted by their families. The relevance of such issues is even higher when the assistance is directed towards cancer patients. The purpose of the paper is analyzing level of costs for alternative assistance programs for cancer patients. The analysis has been carried out for Regione Calabria (Italy). Patients in the sample have been distinguished into several groups according to their health conditions as inferred by a multidimensional evaluation: patients\u2019 multidimensional evaluation has been correlated with the level of costs

The role of mesoscale instabilities in the sting-jet dynamics of windstorm Tini

Sting jets (SJ) occur as an additional region of low-level strong winds in some Shapiro-Keyser-type extra-tropical cyclones. While SJs are widely accepted as being distinct from the warm and cold conveyor belts, the mechanisms responsible for their occurrence are still not fully understood. Here we determine the relative importance of the release of mesoscale instabilities and synoptic-scale cyclone dynamics, so addressing an area of current debate. Numerical weather prediction simulations of a SJ-containing windstorm are analysed and Lagrangian trajectories used to assess the evolution of, and mesoscale atmospheric instabilities (e.g. symmetric and inertial instabilities) in, the descending airstream. The SJ undergoes a two-stage descent: cooling via sublimation followed by a large acceleration accompanied by instability release. Combined tilting and stretching of vorticity play a major role in the local onset of instability on the airstream. Vorticity and frontogenesis fields have a narrow slantwise banded structure in the cloud head and around the SJ; the descending SJ modifies the widespread frontolysis expected from the large-scale dynamics alone in the frontal-fracture region. A coarser-resolution simulation also generates strong winds in the frontal-fracture region, although these are significantly weaker than in the higher-resolution simulation. The SJ airstream in the coarser-resolution simulation undergoes a weaker descent without instability generation and descends in a widespread frontolytic region. Hence, while the SJ undergoes a process of destabilisation that enhances its descent and acceleration in the higher-resolution simulation, enhancing the strong winds already generated by the synoptic-scale cyclone dynamics, this destabilisation does not occur in the SJ produced by a coarser-resolution simulation, resulting in weaker winds. This analysis reveals the synergy between the paradigms of SJ occurrence through the release of mesoscale instabilities and synoptic-scale cyclone dynamics and demonstrates that the current debate may in part be a consequence of the model resolutions used by different studies

Ubiquitin-Specific Protease 8 Mutant Corticotrope Adenomas Present Unique Secretory and Molecular Features and Shed Light on the Role of Ubiquitylation on ACTH Processing

Background: Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been shown to occur in ACTH-secreting pituitary adenomas, thus calling attention to the ubiquitin system in corticotrope adenomas. Objectives: Assess the consequences of USP8 mutations and establish the role of ubiquitin on ACTH turnover in human ACTH-secreting pituitary adenomas. Methods: USP8 mutation status was established in 126 ACTH-secreting adenomas. Differences in ACTH secretion and POMC expression from adenoma primary cultures and in microarray gene expression profiles from archival specimens were sought according to USP8 sequence. Ubiquitin/ACTH coimmunoprecipitation and incubation with MG132, a proteasome inhibitor, were performed in order to establish whether ubiquitin plays a role in POMC/ACTH degradation in corticotrope adenomas. Results: USP8 mutations were identified in 29 adenomas (23%). Adenomas presenting USP8 mutations secreted greater amounts of ACTH and expressed POMC at higher levels compared to USP wild-type specimens. USP8 mutant adenomas were also more sensitive to modulation by CRH and dexamethasone in vitro. At microarray analysis, genes associated with endosomal protein degradation and membrane components were downregulated in USP8 mutant adenomas as were AVPR1B, IL11RA, and PITX2. Inhibition of the ubiquitin-proteasome pathway increased ACTH secretion and POMC itself proved a target of ubiquitylation, independently of USP8 sequence status. Conclusions: Our study has shown that USP8 mutant ACTH-secreting adenomas present a more "typical" corticotrope phenotype and reduced expression of several genes associated with protein degradation. Further, ubiquitylation is directly involved in intracellular ACTH turnover, suggesting that the ubiquitin-proteasome system may represent a target for treatment of human ACTH-secreting adenomas

Inhibition of Rac controls NPM–ALK-dependent lymphoma development and dissemination

Nucleophosmin-anaplastic lymphoma kinase (NPM–ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM–ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM–ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM–ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas

Розвиток духовності особистості в процесі фахової підготовки майбутніх учителів образотворчого мистецтва

(uk) У статті наголошується, що вчитель образотворчого мистецтва виступає носієм не лише спеціальних знань та умінь, але і носієм духовних цінностей. Духовне збагачення і вдосконалення кожної особистості відбувається протягом всього життя в тому числі і в процесі навчання. Гуманізація освіти та естетичне виховання спрямовано на формування гармонійної цілісної особистості, загальнокультурний її розвиток. Засобами естетичного виховання в мистецтві виступає художній образ. Художній образ є відображенням дійсності яке містить в собі не лише суб’єктивний досвід автора, його розуміння та відношення до об’єктів дійсності, але і відбитки культурно-історичного досвіду, естетичних цінностей, але і відбитки культурно-історичного досвіду, естетичних цінностей соціуму загалом. На їх базі і формується всебічно та гармонійно розвинута особистість із вищими моральними цінностями, естетичними канонами та ідеалами.(ru) В статье делается акцент на то, что учитель изобразительного искусства выступает носителем не только специальных знаний и умений, но и носителем духовных ценностей. Духовное обогащение и совершенствование каждой личности происходит на протяжении всей жизни в том числе и в процессе обучения. Гуманизация образования и эстетическое воспитание направлены на формирование гармоничной целостной личности и ее общекультурное развитие. Средством эстетического воспитания в искусстве выступает художественный образ. Художественный образ является отражением действительности, которое содержит в себе не только субъективный опыт автора, его понимание и отношение к объектам действительности, но и отпечатки культурно-исторического опыта, эстетических ценностей социума в целом. На их базе и формируется всесторонне и гармонично развитая личность с высокими моральными ценностями, эстетическими канонами и идеалами.(en) Importance of education in society is determined by the need to raise the national consciousness of the saved and nurturing genuine citizen. Spiritual enrichment and improvement of each individual occurs throughout life including during training. Spirituality determines the direction of all mental, emotional, sensual, strong-willed human qualities and its ability to self yourself as a person. Master of Fine Arts acting carrier not only specialized knowledge and skills, but also a bearer of spiritual values. Humanizing education and aesthetic education aims at forming a harmonious whole person, her general cultural development. Art is an integral part of spiritual culture, a reflection of the artistic representations of the human form of the world of reality. The means of aesthetic education in the art of acting artistic image. Artistic image is a reflection of reality, which contains not only the subjective experience of the author, and understanding related to the objects of reality, but the prints are of cultural and historical experience, the aesthetic values of society as a whole. At their base is formed fully and harmoniously developed personality with higher moral values, aesthetic canons and ideals