759 research outputs found
Risk assessment in avalanche-prone areas
AbstractThis paper addresses the problem of defining a proper method for formal risk analysis in avalanche-prone areas. In this study, risk is defined as the annual probability of being killed by an avalanche for someone living or working permanently in a building under a hazardous hillside. A new methodology to estimate the hazard component of avalanche risk based on the use of dynamic models is introduced. This approach seems to have some advantages over the current methods based on statistical analysis of historic avalanche data. The vulnerability component of risk is formulated as a function of avalanche velocity, according to previous formulations. However, given the lack of knowledge on how avalanche impact damages structures and causes fatalities, the effect on the resulting risk mapping of using different vulnerability relations is explored. The potential of the proposed approach for evaluating the residual risk after the implementation of defensive structural work is discussed
MIR-296 AND ITS TARGET SCRIB IN BREAST CANCER
I microRNA (miRNA) sono piccoli RNA non codificanti che regolano negativamente l'espressione di numerosi mRNA a livello post-trascrizionale. I microRNA sono coinvolti in svariati processi fisiologici (sviluppo, crescita e differenziazione cellulare, apoptosi, etc) e la loro espressione aberrante \ue8 stata riportata in vari tipi di malattie, compresi i tumori.
miR-296 svolge un ruolo importante in diversi tipi di cellule, controllando l'angiogenesi, il differenziamento delle cellule staminali, il potenziale oncogenico e la motilit\ue0. Queste ultime due funzioni sono potenzialmente mediate dall\u2019 inibizione di un suo target, Scrib, una proteina citoplasmatica coinvolta nel mantenimento della polarit\ue0 apico-basale e nella motilit\ue0 delle cellule. Nei tumori il ruolo di miR-296 e del suo target Scrib rimane ancora dibattuto e pochi dati sono disponibili riguardo i carcinomi della mammella.
Data la partecipazione di miR-296 nella regolazione di processi fisiologici di solito alterati nei tumori, abbiamo deciso di valutare i livelli di espressione di miR-296 mediante Real Time PCR e del suo target Scrib mediante immunoistochimica in un'ampia serie di tumori mammari per individuare eventuali correlazioni con i parametri clinici e patologici, utili a fini prognostici e / o predittivi, e per chiarire il ruolo di questo miRNA e del suo target nella tumorigenesi mammaria.
Infine, per valutare se modificando i livelli di miR-296 si potevano avere effetti sulla crescita neoplastica, abbiamo iniettato cellule tumorali mammarie (MDA-MB 231), impiantate in un modello di xenotrapianto, con un precursore di miR-296 o una molecola di controllo e monitorato nel tempo la crescita tumorale.
I nostri dati mostrano che i livelli di miR-296 sono costantemente ridotti nei carcinomi della mammella rispetto al parenchima mammario sano. Inoltre, nel sottogruppo di pazienti con metastasi a distanza, \ue8 stata osservata una correlazione significativa tra la riduzione dei livelli di miR-296 e la disseminazione precoce del tumore.
Per quanto riguarda il target di miR-296, Scrib \ue8 risultato espresso in un numero maggiore di casi nei carcinomi mammari rispetto al parenchima normale e con un\u2019intensit\ue0 maggiore.
L\u2019iniezione diretta di miR-296 in cellule di carcinoma mammario umano impiantate in un modello di xenotrapianto ha inoltre ridotto la crescita del tumore rispetto ai controlli.
I nostri dati confermano il coinvolgimento di miR-296 nella tumorigenesi mammaria, in particolare, una riduzione significativa dei suoi livelli \ue8 stata osservata nei carcinomi rispetto ai controlli normali e la sua forzata riespressione nel modello di xenotrapianto \ue8 risultata efficace nel rallentare la crescita tumorale. Inoltre, l\u2019osservazione che nel gruppo dei pazienti con metastasi a distanza esiste una correlazione significativa tra riduzione dei livelli di miR-296 e lo sviluppo precoce delle metastasi mette in evidenza il ruolo di miR-296 come regolatore della migrazione e dell'invasivit\ue0 cellulare.
Con queste premesse, miR-296 potrebbe rappresentare un nuovo target per la progettazione di farmaci mirati, atti a ripristinare i livelli di miRNA e ad indurre effetti anti-neoplastici.microRNAs (miRNAs) are small non-coding RNAs which negatively regulate the expression of several mRNAs at post-transcriptional level. miRNAs are involved in multiple physiological processes (development, differentiation and cell growth, apoptosis, etc.) and their aberrant expression has been reported in several types of diseases, including tumors.
miR-296 plays important roles in different cell types and cellular pathways, regulating angiogenesis, stem cell differentiation, cell tumorigenic potential and motility. These latter two functions are potentially mediated by inhibition of one of its target, Scrib, a cytoplasmic protein involved in apico-basal cell polarity maintenance and in cell motility. In tumors, the role of miR-296 and of its target Scrib still remains debated, and scarce data are available in breast carcinomas.
Given the role of miR-296 in control of physiological processes normally deregulated in tumors, we aimed to evaluate the expression levels of miR-296 by Real Time PCR and of its target Scrib by immunohistochemistry, in a large series of breast cancers to identify any correlations with clinical and pathological parameters, useful for prognostic and/or predictive purposes, and to clarify the role of this miRNA and its target in mammary tumorigenesis.
Finally, to evaluate if modification of miR-296 levels could have effects on neoplastic growth, we injected breast cancer cells (MDA-MB 231), implanted in a mouse model, with a precursor of miR-296 or a control molecule monitoring tumor growth in time.
miR-296 levels were consistently reduced in human breast cancer tissues compared with non-neoplastic mammary parenchyma. In the subgroup of patients with distant metastases, a significant correlation between reduced miR-296 levels and earlier spread of cancer was detected.
Regarding miR-296 target, breast cancers displayed higher levels of Scrib compared to normal parenchyma, and with a greater intensity.
Direct injection of pre-miR-296 into tumoral masses of a xenograft model significantly decreased tumor growth.
Our data confirm the involvement of miR-296 in breast cancer tumorigenesis, in particular, a significant reduction is observed in infiltrating carcinomas compared to normal controls and experimentally induced restoration of its levels in xenograft assays resulted effective in slowing tumor growth. Furthermore, our observation in the group of patients with distant metastases, showing a significant correlation between reduced miR-296 levels and the earlier onset of distant metastases, highlights the role of miR-296 as a regulator of cell migration and invasion.
With this background, miR-296 could represent a new therapeutic approach and provide a scientific rationale for the design of new drugs with molecular target, appropriate to restore the levels of miRNAs and induce anti-neoplastic effects
A Scalable System Architecture for High-Performance Fault Tolerant Machine Drives
When targeting mission critical applications, the design of the electronic actuation systems needs to consider many requirements and constraints not typical in standard industrial applications. One of these is tolerance to faults, as the unplanned shutdown of a critical subsystem, if not handled correctly, could lead to financial harm, environmental disaster, or even loss of life. One way this can be avoided is through the design of an electric drive systems based on multi-phase machines that can keep operating, albeit with degraded performance, in a partial configuration under fault conditions. Distributed architectures are uniquely suited to meet these challenges, by providing a large degree of isolation between the various components. This paper presents a system architecture suitable for scalable and high-performance fault tolerant machine drive systems. the effectiveness of this system is demonstrated through theoretical analysis and experimental verification on a six-phase machine
Microwave characterization of polymer composite based on Biochar: A comparison of composite behaviour for Biochar and MWCNTs
In this work, Biochar is used as a filler in Epoxy resin for composite preparation. The electrical characteristics of composites are analyzed in function of different filler percentages. Results obtained are compared with composites based on multi-wall carbon nanotubes
Less safety for more efficiency: Water relations and hydraulics of the invasive tree Ailanthus altissima (Mill.) Swingle compared with native Fraxinus ornus L
Invasion of natural habitats by alien trees is a threat to forest conservation. Our understanding of fundamental ecophysiological mechanisms promoting plant invasions is still limited, and hydraulic and water relation traits have been only seldom included in studies comparing native and invasive trees. We compared several leaf and wood functional and mechanistic traits in co-occurring Ailanthus altissima (Mill.) Swingle (Aa) and Fraxinus ornus L. (Fo). Aa is one of the most invasive woody species in Europe and North America, currently outcompeting several native trees including Fo. We aimed at quantifying inter-specific differences in terms of: (i) performance in resource use and acquisition; (ii) hydraulic efficiency and safety; (iii) carbon costs associated to leaf and wood construction; and (iv) plasticity of functional and mechanistic traits in response to light availability. Traits related to leaf and wood construction and drought resistance significantly differed between the two species. Fo sustained higher structural costs than Aa, but was more resistant to drought. The lower resistance to drought stress of Aa was counterbalanced by higher water transport efficiency, but possibly required mechanisms of resilience to drought-induced hydraulic damage. Larger phenotypic plasticity of Aa in response to light availability could also promote the invasive potential of the species
The effect of psychological well-being, psychological help-seeking attitudes and self-esteem on psychological counselor candidates’ psychological symptomsPsikolojik iyi oluş, yardım arama tutumu ve benlik saygısının psikolojik danışman adaylarının psikolojik belirtilerine etkisi
The aim of this research is to examine the effect of psychological well-being, psychological help-seeking attitudes and self-esteem on psychological counselor candidates’ psychological symptoms. A total of 439 students of Psychological Counseling and Guidance Department in the Faculty of Educational Sciences from two universities participated in the research. Research data were obtained by using Psychological Well-Being Scale, Psychological Help-Seeking Attitudes Scale, Rosenberg Self-Esteem Scale and Brief Symptom Inventory. In the research, LISRELL program-Structural Equation Model and SPSS 20 software were employed. In analyses, it was concluded that results of confirmatory factor analysis results and fit indices of structural equation model were generally acceptable. Accordingly, it has been verified with the structural equation model that psychological counselor candidates’ levels of psychological well-being, psychological help-seeking attitudes and psychological symptoms have effect on their level of psychological symptoms. In this respect, it can be understood that considering counseling students’ levels of psychological well-being and self-esteem is important during their educational processes. By supporting counselor candidates’ mental health, a significant contribution will be provided to their personal and professional developments. ÖzetBu araştırmanın amacı, psikolojik danışman adaylarının psikolojik iyi oluşu, psikolojik yardım arama tutumu ve benlik saygısının onların psikolojik belirti düzeylerine etkisinin incelenmesidir. Araştırmaya iki farklı üniversitenin Eğitim Fakültesi Psikolojik Danışmanlık ve Rehberlik bölümünde öğrenim gören 439 danışman adayı katılmıştır. Araştırmanın verileri Psikolojik İyi Oluş Ölçeği, Psikolojik Yardım Almaya İlişkin Tutum Ölçeği, Rosenberg Benlik Saygısı Ölçeği ve Kısa Semptom Envanteri ile elde edilmiştir. Araştırma model geliştirme ve model test etmeye yönelik olup, LİSRELL programı-Yapısal Eşitlik modeli kullanılmıştır. Yapılan analizlerde, doğrulayıcı faktör analizi sonuçlarının ve yapısal eşitlik modeli uyum indekslerinin genel olarak kabul edilebilir düzeyde olduğu belirlenmiştir. Buna göre psikolojik danışman adaylarının psikolojik iyi oluşu, psikolojik yardım arama tutumu ve benlik saygılarının psikolojik belirti düzeyleri üzerinde etkisi olduğu hipotezi doğrulanmıştır. Bu doğrultuda, danışmanlık öğrencilerinin öğretim süreçleri devam ederken psikolojik belirtilerinin incelenmesi, ihtiyaç duyan öğrencilere psikolojik yardım sağlanması ve ruh sağlığının desteklenmesi ile onların profesyonel gelişimlerine de önemli katkı sağlanacağı düşünülmektedir
Long-Term Oral Administration of Theaphenon-E Improves Cardiomyocyte Mechanics and Calcium Dynamics by Affecting Phospholamban Phosphorylation and ATP Production
Background/Aims: Dietary polyphenols from green tea have been shown to possess cardio-protective activities in different experimental models of heart diseases and age-related ventricular dysfunction. The present study was aimed at evaluating whether long term in vivo administration of green tea extracts (GTE), can exert positive effects on the normal heart, with focus on the underlying mechanisms. Methods: The study population consisted of 20 male adult Wistar rats. Ten animals were given 40 mL/day tap water solution of GTE (concentration 0.3%) for 4 weeks (GTE group). The same volume of water was administered to the 10 remaining control rats (CTRL). Then, in vivo and ex vivo measurements of cardiac function were performed in the same animal, at the organ (hemodynamics) and cellular (cardiomyocyte mechanical properties and intracellular calcium dynamics) levels. On cardiomyocytes and myocardial tissue samples collected from the same in vivo studied animals, we evaluated: (1) the intracellular content of ATP, (2) the endogenous mitochondrial respiration, (3) the expression levels of the Sarcoplasmic Reticulum Ca2+-dependent ATPase 2a (SERCA2), the Phospholamban (PLB) and the phosphorylated form of PLB, the L-type Ca2+ channel, the Na+-Ca2+ exchanger, and the ryanodine receptor 2. Results: GTE cardiomyocytes exhibited a hyperdynamic contractility compared with CTRL (the rate of shortening and re-lengthening, the fraction of shortening, the amplitude of calcium transient, and the rate of cytosolic calcium removal were significantly increased). A faster isovolumic relaxation was also observed at the organ level. Consistent with functional data, we measured a significant increase in the intracellular ATP content supported by enhanced endogenous mitochondrial respiration in GTE cardiomyocytes, as well as higher values of the ratios phosphorylated-PLB/PLB and SERCA2/PLB. Conclusions: Long-term in vivo administration of GTE improves cell mechanical properties and intracellular calcium dynamics in normal cardiomyocytes, by increasing energy availability and removing the inhibitory effect of PLB on SERCA2
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