Showing papers by "University of Palermo published in 2012"
Daniel J. Klionsky1, Fábio Camargo Abdalla2, Hagai Abeliovich3, Robert T. Abraham4 +1284 more•Institutions (463)
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
4,316 citations
Utrecht University1, University of Alabama at Birmingham2, Pennsylvania State University3, Columbia University4, University of Palermo5, University of California, San Diego6, Hacettepe University7, Erasmus University Medical Center8, Cardiff University9, University of Siena10, University of Colombo11, University of Adelaide12, Northwestern University13, Imperial College London14, University of Oklahoma15, University of California, Los Angeles16, University of Pennsylvania17
TL;DR: Relevant topics addressed-all dealt with in a systematic fashion-include adolescence, hirsutism and acne, contraception, menstrual cycle abnormalities, quality of life, ethnicity, pregnancy complications, long-term metabolic and cardiovascular health, and finally cancer risk.
1,585 citations
Norwegian University of Science and Technology1, University of Bristol2, University of Leeds3, University of Edinburgh4, King's College London5, Haukeland University Hospital6, Copenhagen University Hospital7, University of Palermo8, Hospital Universitari Arnau de Vilanova9, University Hospital Bonn10, St George's, University of London11
TL;DR: In this paper, the authors provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain.
Abstract: Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common methodology. The recommendations were developed by a writing committee that combined the evidence derived from the systematic reviews with the panellists' evaluations in a co-authored process, and were endorsed by the EAPC Board of Directors. The guidelines are presented as a list of 16 evidence-based recommendations developed according to the Grading of Recommendations Assessment, Development and Evaluation system.
882 citations
TL;DR: This review illustrates the efforts in the search of alternative photocatalysts that are not based on TiO(2), with some exceptions concerning particularly innovative modifications as nanoassembled TiO-based composites with active carbon, graphite and fullerene.
826 citations
TL;DR: In this paper, the authors introduce a new concept of α - ψ -contractive type mappings and establish fixed point theorems for such mappings in complete metric spaces.
Abstract: In this paper, we introduce a new concept of α – ψ -contractive type mappings and establish fixed point theorems for such mappings in complete metric spaces. Starting from the Banach contraction principle, the presented theorems extend, generalize and improve many existing results in the literature. Moreover, some examples and applications to ordinary differential equations are given here to illustrate the usability of the obtained results.
749 citations
TL;DR: The SHARP trial as discussed by the authors showed that sorafenib consistently improved median OS and DCR compared with placebo in patients with advanced HCC, irrespective of disease etiology, baseline tumor burden, performance status, tumor stage and prior therapy.
710 citations
Medical University of Vienna1, Cancer Research UK2, Weizmann Institute of Science3, University of Glasgow4, Imperial College London5, University of Paris6, University of Groningen7, University of Palermo8, University of Cambridge9, French Institute of Health and Medical Research10, Saarland University11, VU University Amsterdam12, Centre national de la recherche scientifique13, Research Institute of Molecular Pathology14, Aalborg University15, University of Texas MD Anderson Cancer Center16, University of British Columbia17
TL;DR: More precise reporting of the parameters that are used to identify CSCs and to attribute responses to them is recommended as key to accelerating an understanding of their biology and developing more effective methods for their eradication in patients.
Abstract: The cancer stem cell (CSC) concept has important therapeutic implications, but its investigation has been hampered both by a lack of consistency in the terms used for these cells and by how they are defined. Evidence of their heterogeneous origins, frequencies and their genomic, as well as their phenotypic and functional, properties has added to the confusion and has fuelled new ideas and controversies. Participants in The Year 2011 Working Conference on CSCs met to review these issues and to propose a conceptual and practical framework for CSC terminology. More precise reporting of the parameters that are used to identify CSCs and to attribute responses to them is also recommended as key to accelerating an understanding of their biology and developing more effective methods for their eradication in patients.
604 citations
TL;DR: In this article, a randomized controlled trial was performed to evaluate the safety and efficacy of enoxaparin, a low-molecular-weight heparin, in preventing portal vein thrombosis (PVT) in patients with advanced cirrhosis.
560 citations
TL;DR: Evidence-based diagnostic and treatment strategies that address not only the amelioration of hirsutism but also the treatment of the underlying etiology is essential for the proper management of affected women, especially considering that hirsUTism is, in most cases, a chronic disorder needing long-term follow-up.
Abstract: Background Hirsutism, defined by the presence of excessive terminal hair in androgen-sensitive areas of the female body, is one of the most common disorders in women during reproductive age. Methods We conducted a systematic review and critical assessment of the available evidence pertaining to the epidemiology, pathophysiology, diagnosis and management of hirsutism. Results The prevalence of hirsutism is ~10% in most populations, with the important exception of Far-East Asian women who present hirsutism less frequently. Although usually caused by relatively benign functional conditions, with the polycystic ovary syndrome leading the list of the most frequent etiologies, hirsutism may be the presenting symptom of a life-threatening tumor requiring immediate intervention. Conclusions Following evidence-based diagnostic and treatment strategies that address not only the amelioration of hirsutism but also the treatment of the underlying etiology is essential for the proper management of affected women, especially considering that hirsutism is, in most cases, a chronic disorder needing long-term follow-up. Accordingly, we provide evidence-based guidelines for the etiological diagnosis and for the management of this frequent medical complaint.
390 citations
TL;DR: The existence of non-celiac wheat sensitivity is demonstrated and the existence of two distinct populations of subjects with WS are suggested: one with characteristics more similar to CD and the other with characteristics pointing to food allergy.
385 citations
TL;DR: It is shown that myeloid DCs uploaded with and activated by NET components induce ANCA and autoimmunity when injected into naive mice, providing the first demonstration that NET structures are highly immunogenic such to trigger adaptive immune response relevant for autoIMmunity.
TL;DR: The authors compared seven structural DSGE models to discretionary fiscal stimulus shocks using seven different fiscal instruments, and compared the results to those of two prominent academic models, such as JEL E12, E13, E52, and E62.
Abstract: The paper subjects seven structural DSGE models, all used heavily by policymaking institutions, to discretionary fiscal stimulus shocks using seven different fiscal instruments, and compares the results to those of two prominent academic DSGE models. There is considerable agreement across models on both the absolute and relative sizes of different types of fiscal multipliers. The size of many multipliers is large, particularly for spending and targeted transfers. Fiscal policy is most effective if it has moderate persistence and if monetary policy is accommodative. Permanently higher spending or deficits imply significantly lower initial multipliers. (JEL E12, E13, E52, E62)
TL;DR: This critical review documents the advances in the development of chiral organocatalysts which are systematically used in ≤3 mol% loading in all the sub-areas of the field, namely aminocatalysis, Brønsted acids and bases, Lewis acids and Base, hydrogen bond-mediated catalysis, phase transfer and N-heterocyclic carbene catalyses.
Abstract: Asymmetric organocatalysis is now recognized as the third pillar of asymmetric synthesis. Recent years have witnessed increasing interest towards the use of highly active and stereoselective organocatalysts. This critical review documents the advances in the development of chiral organocatalysts which are systematically used in ≤3 mol% loading in all the sub-areas of the field, namely aminocatalysis, Bronsted acids and bases, Lewis acids and bases, hydrogen bond-mediated catalysis, phase transfer and N-heterocyclic carbene catalyses (194 references).
TL;DR: How cancers can become insensitive to various inhibitors and potential strategies to overcome this resistance are discussed.
Abstract: // James A. McCubrey 1 , Linda S. Steelman 1 , William H. Chappell 1 , Stephen L. Abrams 1 , Richard A. Franklin 1 , Giuseppe Montalto 2 , Melchiorre Cervello 3 , Massimo Libra 4 , Saverio Candido 4 , Grazia Malaponte 4 , Maria C. Mazzarino 4 , Paolo Fagone 4 , Ferdinando Nicoletti 4 , Jorg Basecke 5 , Sanja Mijatovic 6 , Danijela Maksimovic-Ivanic 6 , Michele Milella 7 , Agostino Tafuri 8 , Francesca Chiarini 9 , Camilla Evangelisti 9 , Lucio Cocco 10 , Alberto M. Martelli 9,10 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA 2 Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy 3 Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare “Alberto Monroy”, Palermo, Italy 4 Department of Bio-Medical Sciences, University of Catania, Catania, Italy 5 Department of Medicine, University of Gottingen, Gottingen, Germany 6 Department of Immunology, Instititue for Biological Research “Sinisa Stankovic”, University of Belgrade, Belgrade, Serbia 7 Regina Elena National Cancer Institute, Rome, Italy 8 Sapienza, University of Rome, Department of Cellular Biotechnology and Hematology, Rome, Italy 9 Institute of Molecular Genetics, National Research Council-Rizzoli Orthopedic Institute, Bologna, Italy 10 Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy Correspondence: James A. McCubrey, email: // Keywords : Targeted Therapy, Therapy Resistance, Cancer Stem Cells, Raf, Akt, PI3K, mTOR Received : September 12, 2012, Accepted : October 18, 2012, Published : October 20, 2012 Abstract The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Targeting these pathways is often complex and can result in pathway activation depending on the presence of upstream mutations (e.g., Raf inhibitors induce Raf activation in cells with wild type (WT) RAF in the presence of mutant, activated RAS ) and rapamycin can induce Akt activation. Targeting with inhibitors directed at two constituents of the same pathway or two different signaling pathways may be a more effective approach. This review will first evaluate potential uses of Raf, MEK, PI3K, Akt and mTOR inhibitors that have been investigated in pre-clinical and clinical investigations and then discuss how cancers can become insensitive to various inhibitors and potential strategies to overcome this resistance.
TL;DR: This article carried out an event study analysis on the reaction of government yield spreads before and after announcements from rating agencies (Standard & Poor's, Moody's, Fitch) to changes in rating notations and outlook.
TL;DR: It is shown here that transgenic mice overexpressing PGC-1 α in dopaminergic neurons are resistant against cell degeneration induced by the neurotoxin MPTP, and RSV and other compounds acting via SIRT1/PGC-1α may prove useful as neuroprotective agents in PD and possibly in other neurological disorders.
Abstract: Mitochondrial dysfunction and oxidative stress occur in Parkinson’s disease (PD), but little is known about the molecular mechanisms controlling these events. Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) is a transcriptional coactivator that is a master regulator of oxidative stress and mitochondrial metabolism. We show here that transgenic mice overexpressing PGC-1α in dopaminergic neurons are resistant against cell degeneration induced by the neurotoxin MPTP. The increase in neuronal viability was accompanied by elevated levels of mitochondrial antioxidants SOD2 and Trx2 in the substantia nigra of transgenic mice. PGC-1α overexpression also protected against MPTP-induced striatal loss of dopamine, and mitochondria from PGC-1α transgenic mice showed an increased respiratory control ratio compared with wild-type animals. To modulate PGC-1α, we employed the small molecular compound, resveratrol (RSV) that protected dopaminergic neurons against the MPTP-induced cell degeneration almost to the same extent as after PGC-1α overexpression. As studied in vitro, RSV activated PGC-1α in dopaminergic SN4741 cells via the deacetylase SIRT1, and enhanced PGC-1α gene transcription with increases in SOD2 and Trx2. Taken together, the results reveal an important function of PGC-1α in dopaminergic neurons to combat oxidative stress and increase neuronal viability. RSV and other compounds acting via SIRT1/PGC-1α may prove useful as neuroprotective agents in PD and possibly in other neurological disorders.
TL;DR: In this article, a general overview on heterogeneous photocatalytic oxidation mechanisms in the presence of TiO 2, with a special focus on conversion of aliphatic and aromatic organic species, is provided.
Abstract: This review provides the reader with a general overview on heterogeneous photocatalytic oxidation mechanisms in the presence of TiO 2 , with a special address to conversion of aliphatic and aromatic organic species. The aim was to clarify the steps of the photo-oxidation of the various classes of compounds and to relate them with the properties of the catalysts and the experimental conditions used. Reactions carried out to perform complete degradation and photocatalytic partial oxidations have been deeply discussed. Recent isotopic studies highlighted new reaction pathways concerning partial oxidation of alcohols to aldehyde and oxidation of benzene while EPR investigations confirmed that not only the photogenerated hole but also the OH radicals are involved in the oxidation of the substrates.
TL;DR: A measurement of the proton-air cross section for particle production at the center-of-mass energy per nucleon of 57 TeV is reported, derived from the distribution of the depths of shower maxima observed with the Pierre Auger Observatory.
Abstract: We report a measurement of the proton-air cross section for particle production at the center-of-mass energy per nucleon of 57 TeV. This is derived from the distribution of the depths of shower maxima observed with the Pierre Auger Observatory: systematic uncertainties are studied in detail. Analyzing the tail of the distribution of the shower maxima, a proton-air cross section of [505 +/- 22(stat)(-36)(+28)(syst)] mb is found.
TL;DR: The inhibitory effect of dasatinib on exosome production and vascular differentiation and signaling reveals a key role for Src in both the leukemia and its microenvironment.
Abstract: Exosomes, microvesicles of endocytic origin released by normal and tumor cells, play an important role in cell-to-cell communication. Angiogenesis has been shown to regulate progression of chronic myeloid leukemia (CML). The mechanism through which this happens has not been elucidated. We isolated and characterized exosomes from K562 CML cells and evaluated their effects on human umbilical endothelial cells (HUVECs). Fluorescent-labeled exosomes were internalized by HUVECs during tubular differentiation on Matrigel. Exosome localization was perinuclear early in differentiation, moving peripherally in cells undergoing elongation and connection. Exosomes move within and between nanotubular structures connecting the remodeling endothelial cells. They stimulated angiotube formation over a serum/growth factor-limited medium control, doubling total cumulative tube length (P = 0.003). Treatment of K562 cells with two clinically active tyrosine kinase inhibitors, imatinib and dasatinib, reduced their total exosome release (P < 0.009); equivalent concentrations of drug-treated exosomes induced a similar extent of tubular differentiation. However, dasatinib treatment of HUVECs markedly inhibited HUVEC response to drug control CML exosomes (P < 0.002). In an in vivo mouse Matrigel plug model angiogenesis was induced by K562 exosomes and abrogated by oral dasatinib treatment (P < 0.01). K562 exosomes induced dasatinib-sensitive Src phosphorylation and activation of downstream Src pathway proteins in HUVECs. Imatinib was minimally active against exosome stimulation of HUVEC cell differentiation and signaling. Thus, CML cell-derived exosomes induce angiogenic activity in HUVEC cells. The inhibitory effect of dasatinib on exosome production and vascular differentiation and signaling reveals a key role for Src in both the leukemia and its microenvironment.
TL;DR: The results show that all eight fluency tasks are sensitive to frontal lobe damage although only the phonemic word and designfluency tasks were specific to the frontal region, supporting the notion that frontal functions comprise a set of specialized cognitive processes, supported by distinct frontal regions.
Abstract: Fluency tasks have been widely used to tap the voluntary generation of responses. The anatomical correlates of fluency tasks and their sensitivity and specificity have been hotly debated. However, investigation of the cognitive processes involved in voluntary generation of responses and whether generation is supported by a common, general process (e.g. fluid intelligence) or specific cognitive processes underpinned by particular frontal regions has rarely been addressed. This study investigates a range of verbal and non-verbal fluency tasks in patients with unselected focal frontal ( n = 47) and posterior ( n = 20) lesions. Patients and controls ( n = 35) matched for education, age and sex were administered fluency tasks including word (phonemic/semantic), design, gesture and ideational fluency as well as background cognitive tests. Lesions were analysed by standard anterior/posterior and left/right frontal subdivisions as well as a finer-grained frontal localization method. Thus, patients with right and left lateral lesions were compared to patients with superior medial lesions. The results show that all eight fluency tasks are sensitive to frontal lobe damage although only the phonemic word and design fluency tasks were specific to the frontal region. Superior medial patients were the only group to be impaired on all eight fluency tasks, relative to controls, consistent with an energization deficit. The most marked fluency deficits for lateral patients were along material specific lines (i.e. left—phonemic and right—design). Phonemic word fluency that requires greater selection was most severely impaired following left inferior frontal damage. Overall, our results support the notion that frontal functions comprise a set of specialized cognitive processes, supported by distinct frontal regions.
* Abbreviations
: LIFG
: left inferior frontal gyrus
APM
: advanced progressive matrices
TL;DR: The knowledge of atherosclerosis as an inflammatory disease offers the opportunity to develop novel therapeutic strategies targeting the inflammatory component of the disease.
Abstract: In many ways, atherosclerosis is a chronic inflammatory disorder and this issue is confirmed by recent investigations of that have focused on inflammation, providing new insight into mechanisms of disease. Several recent studies have addressed the role of chemokines in leukocyte accumulation in atherosclerosis, extending our knowledge and understanding of the complex and cell typespecific functions of chemokines in atherosclerosis. Activated T-lymphocytes within the atherosclerotic vessel wall express the CD40 ligand surface molecule, known to play a major role in several immunological pathways. In addition to activated T-lymphocytes, functional CD40 and CD40L are coexpressed by human vascular endothelial cells, smooth muscle cells and human macrophages in vitro as well as in situ in human atherosclerotic lesions. Recent studies indicate that CD40L activates atheroma-associated cells by promoting the expression of molecules thought to be involved in atherosclerosis, such as adhesion molecules, cytokines, matrix metalloproteinases, and tissue factor. Atherosclerosis starts with an innate immune response involving the recruitment and activation of monocytes macrophages that respond to an excessive accumulation of modified lipids within the arterial wall, followed by an adaptive immune response involving antigen-specific T lymphocytes. Effector T cells recognize modified auto-antigens such as oxidized LDL and heat shock proteins (i.e. HSP-60) that are presented by antigen-presenting cells such as macrophages or dendritic cells. The accumulation of inflammatory cells within the arterial wall leads to local production of chemokines, interleukins and proteases that enhance the influx of monocytes and lymphocytes, thereby promoting the progression of atherosclerotic lesions Recent reports have helped explain some of these questions by pointing to a role of contact dependent interaction between CD40 and CD40 ligand (CD40L, renamed CD154) as a stimulus for atheroma-associated cells. Also Macrophages play important roles in the progression of atherosclerosis by exhibiting unique characteristics under the various stimuli, evolving the plaque instability, thrombus formation and remodeling. Macrophage recruitment by abnormal endothelium over developing atherosclerotic plaques, is aided by endothelial expression of adhesion molecules (ICAM-1, VCAM, ELAM). The knowledge of atherosclerosis as an inflammatory disease offers the opportunity to develop novel therapeutic strategies targeting the inflammatory component of the disease.
TL;DR: In this article, the concept of a partial Hausdorff metric was introduced for multi-valued mappings on partial metric space and proved an analogous to the well-known Nadler's fixed point theorem.
TL;DR: It was found that SCEM-UA and AMALGAM produce results quicker than GLUE in terms of required number of simulations, but modellers should select the method which is most suitable for the system they are modelling, as GLUE requires the lowest modelling skills and is easy to implement.
University of Turin1, University of Cagliari2, University of Würzburg3, National Institutes of Health4, University of Sassari5, University of Genoa6, University of Palermo7, The Catholic University of America8, Seconda Università degli Studi di Napoli9, University of Bari10, National Research Council11, Sapienza University of Rome12, University of Siena13
TL;DR: The phenotype of amyotrophic lateral sclerosis cases carrying C9ORF72 hexanucleotide repeat expansions was described by providing a detailed clinical description of affected cases from representative multi-generational kindreds, and by analysing the age of onset, gender ratio and survival in a large cohort of patients with familial amyotroph lateral sclerosis.
Abstract: A large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72, a gene located on chromosome 9p21, has been recently reported to be responsible for ~40% of familial amyotrophic lateral sclerosis cases of European ancestry. The aim of the current article was to describe the phenotype of amyotrophic lateral sclerosis cases carrying the expansion by providing a detailed clinical description of affected cases from representative multi-generational kindreds, and by analysing the age of onset, gender ratio and survival in a large cohort of patients with familial amyotrophic lateral sclerosis. We collected DNA and analysed phenotype data for 141 index Italian familial amyotrophic lateral sclerosis cases (21 of Sardinian ancestry) and 41 German index familial amyotrophic lateral sclerosis cases. Pathogenic repeat expansions were detected in 45 (37.5%) patients from mainland Italy, 12 (57.1%) patients of Sardinian ancestry and nine (22.0%) of the 41 German index familial amyotrophic lateral sclerosis cases. The disease was maternally transmitted in 27 (49.1%) pedigrees and paternally transmitted in 28 (50.9%) pedigrees (P = non-significant). On average, children developed disease 7.0 years earlier than their parents [children: 55.8 years (standard deviation 7.9), parents: 62.8 (standard deviation 10.9); P = 0.003]. Parental phenotype influenced the type of clinical symptoms manifested by the child: of the 13 cases where the affected parent had an amyotrophic lateral sclerosis-frontotemporal dementia or frontotemporal dementia, the affected child also developed amyotrophic lateral sclerosis-frontotemporal dementia in nine cases. When compared with patients carrying mutations of other amyotrophic lateral sclerosis-related genes, those with C9ORF72 expansion had commonly a bulbar onset (42.2% compared with 25.0% among non-C9ORF72 expansion cases, P = 0.03) and cognitive impairment (46.7% compared with 9.1% among non-C9ORF72 expansion cases, P = 0.0001). Median survival from symptom onset among cases carrying C9ORF72 repeat expansion was 3.2 years lower than that of patients carrying TARDBP mutations (5.0 years; 95% confidence interval: 3.6-7.2) and longer than those with FUS mutations (1.9 years; 95% confidence interval: 1.7-2.1). We conclude that C9ORF72 hexanucleotide repeat expansions were the most frequent mutation in our large cohort of patients with familial amyotrophic lateral sclerosis of Italian, Sardinian and German ancestry. Together with mutation of SOD1, TARDBP and FUS, mutations of C9ORF72 account for ~60% of familial amyotrophic lateral sclerosis in Italy. Patients with C9ORF72 hexanucleotide repeat expansions present some phenotypic differences compared with patients with mutations of other genes or with unknown mutations, namely a high incidence of bulbar-onset disease and comorbidity with frontotemporal dementia. Their pedigrees typically display a high frequency of cases with pure frontotemporal dementia, widening the concept of familial amyotrophic lateral sclerosis.
01 Jan 2012
TL;DR: In this article, el riesgo se corresponde con la probabilidad de sufrir algun dano a futuro, i.e., the probability of a dano occurring in the future.
Abstract: ?Por que sucede la crisis economica de 2008? ?fue provocada por los Estados Unidos como una estrategia expansionista o una simple falla del sistema capitalista? En perspectiva, el mundo de las relaciones productivas impacta sobre el social y viceversa. No es extrano observar el interes de las ciencias sociales por el estudio del riesgo en los ultimos anos. Para los especialistas, el riesgo se corresponde con la probabilidad de sufrir algun dano a futuro...
TL;DR: In this article, the authors consider a system of two independently evolving qubits, each locally interacting with a classical random external field, and explain the revivals in terms of correlations in a classical-quantum state of the environments and the qubits.
Abstract: Revivals of quantum correlations have often been explained in terms of back-action on quantum systems by their quantum environment(s). Here we consider a system of two independently evolving qubits, each locally interacting with a classical random external field. The environments of the qubits are also independent, and there is no back-action on the qubits. Nevertheless, entanglement, quantum discord, and classical correlations between the two qubits may revive in this model. We explain the revivals in terms of correlations in a classical-quantum state of the environments and the qubits. Although classical states cannot store entanglement on their own, they can play a role in storing and reviving entanglement. It is important to know how the absence of back-action, or modeling an environment as classical, affects the kind of system time evolutions one is able to describe. We find a class of global time evolutions where back-action is absent and for which there is no loss of generality in modeling the environment as classical. Finally, we show that the revivals can be connected with the increase of a parameter used to quantify non-Markovianity of the single-qubit dynamics.
TL;DR: In this paper, the authors present the results of the work done by a panel of experts participating in the European Union COST (COoperation in Scientific and Technological research) ACTION B26 on OSA, with the endorsement of the European Respiratory Society (ERS) and the European Society of Hypertension (ESH).
Abstract: This article is aimed at addressing the current state of the art in epidemiology, pathophysiology, diagnostic procedures and treatment options for appropriate management of obstructive sleep apnea (OSA) in cardiovascular (particularly hypertensive) patients, as well as for the management of cardiovascular diseases (particularly arterial hypertension) in OSA patients. The present document is the result of the work done by a panel of experts participating in the European Union COST (COoperation in Scientific and Technological research) ACTION B26 on OSA, with the endorsement of the European Respiratory Society (ERS) and the European Society of Hypertension (ESH). These recommendations are particularly aimed at reminding cardiovascular experts to consider the occurrence of sleep-related breathing disorders in patients with high blood pressure. They are at the same time aimed at reminding respiration experts to consider the occurrence of hypertension in patients with respiratory problems at night.
TL;DR: It is shown that high CO2 / low pH conditions of OA decrease, rather than increase, concentrations of phenolic protective substances in seagrasses and eurysaline marine plants, tempering recent predictions that seagRasses would necessarily be “winners” in a highCO2 world.
Abstract: Rising atmospheric CO2 often triggers the production of plant phenolics, including many that serve as herbivore deterrents, digestion reducers, antimicrobials, or ultraviolet sunscreens. Such responses are predicted by popular models of plant defense, especially resource availability models which link carbon availability to phenolic biosynthesis. CO2 availability is also increasing in the oceans, where anthropogenic emissions cause ocean acidification, decreasing seawater pH and shifting the carbonate system towards further CO2 enrichment. Such conditions tend to increase seagrass productivity but may also increase rates of grazing on these marine plants. Here we show that high CO2 / low pH conditions of OA decrease, rather than increase, concentrations of phenolic protective substances in seagrasses and eurysaline marine plants. We observed a loss of simple and polymeric phenolics in the seagrass Cymodocea nodosa near a volcanic CO2 vent on the Island of Vulcano, Italy, where pH values decreased from 8.1 to 7.3 and pCO2 concentrations increased ten-fold. We observed similar responses in two estuarine species, Ruppia maritima and Potamogeton perfoliatus, in in situ Free-Ocean-Carbon-Enrichment experiments conducted in tributaries of the Chesapeake Bay, USA. These responses are strikingly different than those exhibited by terrestrial plants. The loss of phenolic substances may explain the higher-than-usual rates of grazing observed near undersea CO2 vents and suggests that ocean acidification may alter coastal carbon fluxes by affecting rates of decomposition, grazing, and disease. Our observations temper recent predictions that seagrasses would necessarily be “winners” in a high CO2 world.
TL;DR: The results suggest for the first time that exosomes released from CML cells directly affect endothelial cells modulating the process of neovascularization.
Abstract: Our study is designed to assess if exosomes released from chronic myelogenous leukemia (CML) cells may modulate angiogenesis. We have isolated and characterized the exosomes generated from LAMA84 CML cells and demonstrated that addition of exosomes to human vascular endothelial cells (HUVEC) induces an increase of both ICAM-1 and VCAM-1 cell adhesion molecules and interleukin-8 expression. The stimulation of cell-cell adhesion molecules was paralleled by a dose-dependent increase of adhesion of CML cells to a HUVEC monolayer. We further showed that the treatment with exosomes from CML cells caused an increase in endothelial cell motility accompanied by a loss of VE-cadherin and β-catenin from the endothelial cell surface. Functional characterization of exosomes isolated from CML patients confirmed the data obtained with exosomes derived from CML cell line. CML exosomes caused reorganization into tubes of HUVEC cells cultured on Matrigel. When added to Matrigel plugs in vivo, exosomes induced ingrowth of murine endothelial cells and vascularization of the Matrigel plugs. Our results suggest for the first time that exosomes released from CML cells directly affect endothelial cells modulating the process of neovascularization.
TL;DR: In this paper, an original laboratory scale planar geometry Membrane Distillation unit was designed, built and tested for future coupling with solar energy, in order to allow for multi-stage arrangement, compactness, internal heat recovery and possible integration with a polymeric heat exchanger for final brine heating.
Abstract: Membrane Distillation (MD) processes are gaining growing interest among novel desalination technologies, in particular for small scale applications also coupled with non-conventional energy sources In the present work an original laboratory scale planar geometry Membrane Distillation unit was designed, built and tested for future coupling with solar energy Though conceptually simple, the original geometry was developed in order to allow for multi-stage arrangement, compactness, internal heat recovery and possible integration with a polymeric heat exchanger for final brine heating by means of solar energy or waste heat The laboratory scale unit was tested in order to investigate the effect of operating conditions, ie hot feed temperature and flow rate, on the process performance, with particular attention paid to parameters relevant to the design of the system coupled with solar energy Also the effect of different airgap configurations was investigated, namely (i) free airgap, (ii) permeate-gap and (iii) partial vacuum airgap arrangements In parallel, a simplified predictive model based on heat and mass balance and transport equations was implemented and validated against experimental data collected The validated model was used to simulate the behavior of multi-stage units based on the planar geometry investigated in the present work for the purpose of a simplified economic analysis of the system and for the conceptual design of the solar energy powered MD unit to be installed at Universita di Palermo, where further testing will be performed