Alcohol Use, Abuse, and Dependency in Shanghai

The use of alcohol for social and ceremonial occasions was recorded in Chinese history as early as 1760 B.C. during the Yin Dynasty (Ci-Hai Encyclopedia, 1979:936). The cultural tradition of ancient China placed alcoholic beverages at the center of social occasions, which presumably was the origin of the adage: Without wine, there is no li (or etiquette). Thus, the use of alcoholic beverages has always been accompanied by the concept of propriety and the discharging of one\u27s role obligations m social functions, rather than that of personal indulgence

New Insight into the Anti-liver Fibrosis Effect of Multitargeted Tyrosine Kinase Inhibitors: From Molecular Target to Clinical Trials

Tyrosine kinases (TKs) is a family of tyrosine protein kinases with important functions in the regulation of a broad variety of physiological cell processes. Overactivity of TK disturbs cellular homeostasis and has been linked to the development of certain diseases, including various fibrotic diseases. In regard to liver fibrosis, several TKs, such as vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and epidermal growth factor receptor (EGFR) kinases, have been identified as central mediators in collagen production and potential targets for anti-liver fibrosis therapies. Given the essential role of TKs during liver fibrogenesis, multitargeted inhibitors of aberrant TK activity, including sorafenib, erlotinib, imatinib, sunitinib, nilotinib, brivanib and vatalanib, have been shown to have potential for treating liver fibrosis. Beneficial effects are observed by researchers of this field using these multitargeted TK inhibitors in preclinical animal models and in patients with liver fibrosis. The present review will briefly summarize the anti-liver fibrosis effects of multitargeted TK inhibitors and molecular mechanisms

Piezoelectric vibration energy harvester actuated by seismic excitation

LAUREA MAGISTRALELa tecnologia basata su MEMS è in continuo sviluppo e trova la sua applicazione in molteplici ambiti. In particolare, nell'ingegneria civile essa svolge un ruolo determinante per il monitoraggio delle strutture: i cosiddetti sensori, infatti, vengono impiegati nel controllo dello stato di sollecitazioni nelle strutture civili. Negli ultimi anni, ai fini di migliorare la versatilità nell'utilizzo di questi sensori, gli energy harvester, un’altra applicazione della tecnologia dei MEMS, sono stati combinati con i MEMS. Nacque così il concetto di sensori autonomi, sensori in grado di raccogliere l'energia dall'ambiente. Essi costituiscono l'oggetto della presente tesi, che si occupa in particolare di valutare la fattibilità di un specifico harvester-sensor in grado di funzionare in maniera autonoma nel monitoraggio delle strutture in zone sismiche. La presente tesi è suddivisa in due parti: la prima riguarda la verifica della capacità di raccogliere l'energia dal movimento sismico; mentre la seconda consiste nel valutare le possibilità di sfruttare tale energia raccolta nelle applicazioni pratiche. Nella prima parte è stato utilizzato un approccio disaccoppiato per risolvere il problema: è stato progettato un cantilever piezoelectric harvester attraverso la teoria dell'oscillatore ad un grado di libertà; successivamente è stata verificata la capacità di raccogliere energia sotto l'azione del sisma, tramite l'analisi agli elementi finiti. Inoltre, per comprendere meglio il comportamento dinamico del cantilever, sono state condotte diverse analisi parametriche e introdotti vari accorgimenti di progettazione per migliorare il modello, ai fini di aumentare la prestazione nella raccolta di energia. Una volta accertata la capacità di raccogliere l'energia sismica, diverse idee di come sfruttare quest'ultima sono state discusse. Il primo campo di applicazione consiste nella registrazione dei dati effettuata dall'harvester, che funge da sensore. Quando la sollecitazione sismica supera un valore soglia, l'harvester sfrutta l'energia raccolta fino a quel momento per registrare tale evento. Un'altra più importante applicazione è il sistema di early warning, in base al quale l'harvester sfrutta l'energia raccolta per attivare un allarme quando una certa soglia è superata. È stato dimostrato che l'energia raccolta dai moti sismici è sufficiente per la registrazione dei dati, mentre lo stesso non si può affermare per la trasmissione. Ciò comporta l'introduzione di altre strategie di progettazione per avere energia sufficiente.Micro Electro-Mechanical Systems (MEMS) technology is continuously developing and finds today numerous applications in many fields. In particular, in civil engineering it is becoming an increasingly relevant and in the future will play a determinant role for structural health monitoring: sensors are employed to control the solicitation state of civil structures. In recent years, to improve the versatility of these sensors, energy harvesters, which are similar devices based on MEMS technology, have been studied to be combined with them. The concept of autonomous sensors able to work with energy harvested from environment was born. Based on such fact, the idea of this dissertation was originated, it focuses on the feasibility of a specific harvester-sensor that could be employed in structural monitoring in active seismic zones. For this purpose, the dissertation is divided into two parts: the first one consists in seismic micro-energy harvesting assessment; while the second one focuses on how to exploit the harvested energy in practical applications. In the first part a complete uncoupled approach is employed to solve the problem: a cantilever piezoelectric harvester has been designed by applying the single degree freedom theory, at a later time its energy harvesting capacity under seismic motion is assessed through finite element (FE) analysis. Moreover, to better understand the cantilever dynamic behaviour, a parametric analysis has been performed and different design choices are introduced to enhance the model, and to increase the seismic energy harvesting performance. Once ensured the cantilever harvesting capacity, different ideas of exploiting this harvested energy are discussed. The first application field consists in data recording: the harvester is treated as a sensor and, when the seismic excitation overpasses a defined threshold, harvester exploits the energy scavenged to record this event. Another more important application is early warning: based on the same idea, instead of using for data recording, the harvested energy should provide with an alarm when the defined threshold is overpassed. It has been proved that the energy harvested from the seismic motion is sufficient for data recording, while is not for data transmission. This means that other design strategies should be introduced to provide sufficient energy

M gene reassortment in H9N2 influenza virus promotes early infection and replication: contribution to rising virus prevalence in chickens in China

Segment reassortment and base mutagenesis of influenza A viruses are the primary routes to the rapid evolution of high fitness virus genotypes. We recently described a predominant G57 genotype of avian H9N2 viruses that caused country-wide outbreaks in chickens in China during 2010-2013 which led to the zoonotic emergence of H7N9 viruses. One of the key features of the G57 genotype is the substitution of the earlier BJ/94-like M gene with the G1-like M gene of quail origin. We report here on the functional significance of the G1-like M gene in H9N2 viruses in conferring increased infection severity and infectivity in primary chicken embryonic fibroblasts and chickens. H9N2 virus housing the G1-like M gene, in place of BJ/94-like M gene, showed early surge in viral mRNA and vRNA transcription that were associated with enhanced viral protein production, and with early elevated release of progeny virus comprising largely spherical rather than filamentous virions. Importantly, H9N2 virus with G1-like M gene conferred extrapulmonary virus spread in chickens. Five highly represented signature amino acid residues (37A, 95K, 224N and 242N in M1 protein, and 21G in M2 protein) encoded by the prevalent G1-like M gene were demonstrated as prime contributors to enhanced infectivity. Therefore, the genetic evolution of M gene in H9N2 virus increases reproductive virus fitness, indicating its contribution to rising virus prevalence in chickens in China. Importance We recently described the circulation of a dominant genotype (G57) of H9N2 viruses in country-wide outbreaks in chickens in China, which was responsible through reassortment for the emergence of H7N9 viruses that cause severe human infections. A key feature of the G57 genotype H9N2 virus is the presence of quail origin G1-like M gene which had replaced the earlier BJ/94-like M gene. We found that H9N2 virus with G1-like M gene, but not BJ/94-like M gene, showed early surge in progeny virus production, more severe pathology and extrapulmonary virus spread in chickens. Five highly represented amino acid residues in M1 and M2 proteins derived from G1-like M gene were shown to mediate enhanced virus infectivity. These observations enhance what we currently know about the roles of reassortment and mutations on virus fitness and have implications for assessing the potential of variant influenza viruses that can cause rising prevalence in chickens