Motion control development in the TIA Portal for the MS260 binding and wrapping machine

The MS260 is a biding and wrapping machine. It is an end-of-line machine designed and created by IMA S.p.A and, in particular, by the division dedicated to the end-of-line, i.e. IMA BFB. The thesis work is concentrated on the development of the machine by exclusively using Siemens hardware and software. In particular, the MS260 analysed is divided into two parts. The PLC part is characterized by Siemens hardware with the relative algorithm developed through the TIA Portal software. At the same time, the motion control part is entirely characterized by elements linked to the Schneider world. Drives and motors belong to the aforementioned company, as well as the algorithm is developed through the native software MachineExpert. The objective of the thesis is, then, divided into two parts. First of all, it is necessary to study the characteristics of the machine. This allows to select a suitable hardware for the new code. The study of the motor performances allow an optimal choice of the agitations from the Siemens catalog. Furthermore, the replacement of the drives requires also the change of the PLC, passing to an hardware capable of handling more advanced control. Secondly, the motion control algorithm must be developed and integrated. To do this, some Siemens libraries are exploited while others must be created in order to exploit non-native functions. The final integration foresees the adaptation of the PLC code to the new organization of the motion algorithm and the partial modification of the HMI software to add the new functionalities

Monitoring large cloud-based systems

Large scale cloud-based services are built upon a multitude of hardware and software resources, disseminated in one or multiple data centers. Controlling and managing these resources requires the integration of several pieces of software that may yield a representative view of the data center status. Today’s both closed and open-source monitoring solutions fail in different ways, including the lack of scalability, scarce representativity of global state conditions, inability in guaranteeing persistence in service delivery, and the impossibility of monitoring multi-tenant applications. In this paper, we present a novel monitoring architecture that addresses the aforementioned issues. It integrates a hierarchical scheme to monitor the resources in a cluster with a distributed hash table (DHT) to broadcast system state information among different monitors. This architecture strives to obtain high scalability, effectiveness and resilience, as well as the possibility of monitoring services spanning across different clusters or even different data centers of the cloud provider. We evaluate the scalability of the proposed architecture through a bottleneck analysis achieved by experimental results

Biological analysis of the in-vitro effects of homologous recombination inhibition and its use in cancer treatment through synthetic lethality

Synthetic lethality represents an anticancer strategy that targets tumor specific gene defects. One of the most studied application is the use of PARP inhibitors (e.g. olaparib) in BRCA1/2-less cancer cells. In BRCA2-defective tumors, olaparib (OLA) inhibits DNA single-strand break repair, while BRCA2 mutations hamper homologous recombination (HR) repair. The simultaneous impairment of those pathways leads BRCA-less cells to death by synthetic lethality. The projects described in this thesis were aimed at extending the use of OLA in cancer cells that do not carry a mutation in BRCA2 by combining this drug with compounds that could mimic a BRCA-less environment via HR inhibition. We demonstrated the effectiveness of our “fully small-molecule induced synthetic lethality” by using two different approaches. In the direct approach (Project A), we identified a series of neo-synthesized compounds (named RAD51-BRCA2 disruptors) that mimic BRCA2 mutations by disrupting the RAD51-BRCA2 interaction and thus the HR pathway. Compound ARN 24089 inhibited HR in human pancreatic adenocarcinoma cell line and triggered synthetic lethality by synergizing with OLA. Interestingly, the observed synthetic lethality was triggered by tackling two biochemically different mechanisms: enzyme inhibition (PARP) and protein-protein disruption (RAD51-BRCA2). In the indirect approach (Project B), we inhibited HR by interfering with the cellular metabolism through inhibition of LDH activity. The obtained data suggest an LDH-mediated control on HR that can be exerted by regulating either the energy supply needed to this repair mechanism or the expression level of genes involved in DNA repair. LDH inhibition also succeeded in increasing the efficiency of OLA in BRCA-proficient cell lines. Although preliminary, these results highlight a complex relationship between metabolic reactions and the control of DNA integrity. Both the described projects proved that our “fully small-molecule-induced synthetic lethality” approach could be an innovative approach to unmet oncological needs

RNA and DNA viruses: role of cross-species transmission in the viral evolution

L’ampliamento dello spettro d’ospite è strettamente connesso al processo evolutivo a cui i virus sono assoggettati e rappresenta una notevole sfida alla loro capacità di adattarsi. L’attitudine a superare le barriere di specie è conseguente alla costante e relativamente rapida evoluzione che caratterizza i virus; allo stesso tempo, la forza selettiva esercitata dal nuovo ospite rappresenterà un ulteriore stimolo per le capacità adattative del virus. Ad oggi, i meccanismi genetici ed evolutivi responsabili del salto di specie virale, cioè la trasmissione di un virus da un ospite tradizionale ad uno precedentemente resistente all’infezione, sono parzialmente sconosciuti. Nel seguente lavoro verranno presentati gli studi effettuati sulle dinamiche evolutive caratterizzanti virus a RNA e a DNA in cui si sono osservate variazioni dello spettro d’ospite. Gli studi hanno riguardato i coronavirus, con particolare riferimento al ruolo svolto dai pipistrelli nell’evoluzione dei coronavirus SARS-correlati, e l’importanza del gatto nell’evoluzione dei parvovirus dei carnivori. Nella prima sezione saranno mostrate le correlazioni genetiche dei coronavirus identificati in Italia nei pipistrelli appartenenti alla specie Rhinolophus ferrumequinum con i ceppi europei e del resto del mondo, allo scopo di chiarire l’origine evolutiva dei coronavirus dei pipistrelli correlati al virus della SARS (Bat-SARS-like CoV) europei, gli eventi migratori che hanno caratterizzato la loro diffusione nel continente e le potenziali ripercussioni sulla salute pubblica. Nella seconda sezione saranno evidenziate le caratteristiche molecolari dei ceppi di parvovirus circolanti nella popolazione felina, valutandone la diversità di sequenza e la complessità genetica, allo scopo di ottenere importanti informazioni in merito all’evoluzione del virus e alle interazioni tra il parvovirus e l’ospite.The cross-species transmission is closely related to viral evolution and represents a challenge for viral adaptability. The capacity to overcome the species barriers is due to the constant and relatively rapid evolution that characterizes the viruses. At the same time, the selective force exerted by the new host will provide a further stimulus for the adaptive capacity of the virus. To date, the genetic and evolutionary mechanisms responsible for the species jump, namely the transmission of a virus from the traditional host to a new host previously resistant to infection, are partially unknowns. Aim of this work is to present studies conducted on the evolutionary dynamics characterizing RNA and DNA viruses subjected to cross-species transmission. Research has been done on coronavirus, focusing on the role played by bats in the evolution of SARS-related coronavirus, and on parvovirus, specifically on the role of the cat in carnivores parvoviruses evolution. The first section will show the genetic correlations between coronaviruses identified in Italy in Rhinolophus ferrumequinum bats, with strains identified in Europe and in the rest of the world, in order to clarify the evolutionary origin of the bat coronaviruses related to SARS virus (Bat-SARS-like CoV) in our continent, the migratory events that have characterized their spread, and their potential impact on public health. In the second section the molecular characteristics of the strains of parvovirus circulating in cats population will be highlighted, evaluating their sequence diversity and genetic complexity, in order to obtain important information on viral evolution and interactions between parvovirus and host

Detection of a virus related to betacoronaviruses in Italian greater horseshoe bats.

SUMMARYThe association between coronaviruses and bats is a worldwide phenomenon and bats belonging to genus Rhinolophus are the reservoir host for several coronaviruses, including a large number of viruses closely related genetically to severe acute respiratory syndrome-coronavirus (SARS-CoV). We carried out a survey in colonies of Italian bats (Rhinolophus ferrumequinum) for the presence of coronaviruses. Two of 52 R. ferrumequinum captured from different Italian areas tested positive by reverse transcription–PCR for a fragment of RNA-dependent RNA polymerase (RdRp) gene of viruses related to Coronavirus. Phylogenetic analysis revealed close correlations between one of the positive samples and SARS-related CoV belonging to the genus Betacoronavirus

Clinicopathological Findings in Cats Tested for Feline Immunodeficiency Virus (FIV) and Feline Leukaemia Virus (FeLV)

Abstract This retrospective study aimed to evaluate the clinicopathological changes in a population of cats tested for feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV), in an Italian Veterinary University Hospital, in the period between January 2002 and May 2016. During the period of 14 years, 1834 cats were tested, and of these 241/1834 (13.1%) were positive for FIV antibodies and 92/1834 (5%) cats were positive for FeLV antigen. These data confirm the presence of a high prevalence of these viruses on Italian territory. To the authors' knowledge, this study describes findings that have never been evaluated before, such as iron status in retrovirus-infected cats and urinalysis in FeLV-positive cats. In this study, FIV-positive cats were more likely to have higher serum protein concentration and lower albumin-globulin ratio than other groups of cats. Lower urine specific gravity and higher urine protein to creatinine ratio were also detected for FIV-positive cats when compared with negative and healthy cats. FeLV-positive cats were more likely to have cytopenia, decreased haemoglobin, haematocrit and RBC compared with other groups of cats. The data obtained underline the importance of considering retroviral infections in the presence of a broad spectrum of risk factors and laboratory anomalies

A Real-Time PCR Assay for Bat SARS-Like Coronavirus Detection and Its Application to Italian Greater Horseshoe Bat Faecal Sample Surveys

Bats are source of coronaviruses closely related to the severe acute respiratory syndrome (SARS) virus. Numerous studies have been carried out to identify new bat viruses related to SARS-coronavirus (bat-SARS-like CoVs) using a reverse-transcribed-polymerase chain reaction assay. However, a qualitative PCR could underestimate the prevalence of infection, affecting the epidemiological evaluation of bats in viral ecology. In this work an SYBR Green-real time PCR assay was developed for diagnosing infection with SARS-related coronaviruses from bat guano and was applied as screening tool in a survey carried out on 45 greater horseshoe bats (Rhinolophus ferrumequinum) sampled in Italy in 2009. The assay showed high sensitivity and reproducibility. Its application on bats screening resulted in a prevalence of 42%. This method could be suitable as screening tool in epidemiological surveys about the presence of bat-SARS-like CoVs, consequently to obtain a more realistic scenario of the viral prevalence in the population

Anaplasma phagocytophilum infection in thrombocytopenic dogs

Anaplasma and Ehrlichia spp. are tick-transmitted bacteria of clinical relevance in European dogs. The diagnosis of infection is often difficult due to the wide spectrum of disease caused by them. During infection, reduction in platelet count is considered the most common haematological abnormality, frequently representing the sole alteration in asymptomatic dogs. In this study, the presence of bacteria belonging to the genera Anaplasma and Ehrlichia was investigated in Northern Italy in blood samples from 159 thrombocytopenic dogs using a polymerase chain reaction (PCR) assay amplifying a portion of the heat shock gene (groEL). Obtained amplicons were sequenced and analysed. Two dogs were positive for A. phagocytophilum, while A. platys and E. canis were not detected. None of the PCR-positive dogs were diagnosed at the time of hospital admission, even in the presence of clinical signs and clinicopathological abnormalities potentially related to A. phagocytophilum infection. Nucleotide sequence analysis showed that the 2 detected strains belonged to the cluster Europe 1 and were different from each other. This study confirms the presence of A. phagocytophilum infections in dogs of Northern Italy, causing clinical signs and laboratory abnormalities that could not be properly diagnosed and treated

Severe, diffuse fibrinonecrotic pleuropneumonia in a cat affected by multiple viral infection

This communication describes the coinfection with feline panleukopenia virus (FPV), feline herpesvirus 1 (FeHV-1), feline calicivirus (FCV) and feline coronavirus (FCoV) in a 1 year\u2011old domestic cat living in a feline shelter. The cat was referred to veterinary hospital with clinical signs related to diffuse gastro-intestinal inflammation, it had developed a severe pneumopathy with fibrinous exudation in all body cavities and died 8 days after initial presentation. Pathological findings and biomolecular diagnostic test results were compatible with an initial FPV infection that, in consequence of the lymphoid depletion, has fostered coinfection or reactivation of chronic-latent infections with FeHV-1, FCV, and FCoV. In the reported case, the simultaneous presence of different viruses exacerbated the clinical status of the host, resulting in multiple organ damage and leading it to its death

Genetic complexity and multiple infections with more Parvovirus species in naturally infected cats

Parvoviruses of carnivores include three closely related autonomous parvoviruses: canine parvovirus (CPV), feline panleukopenia virus (FPV) and mink enteritis virus (MEV). These viruses cause a variety of serious diseases, especially in young patients, since they have a remarkable predilection for replication in rapidly dividing cells. FPV is not the only parvovirus species which infects cats; in addition to MEV, the new variants of canine parvovirus, CPV-2a, 2b and 2c have also penetrated the feline host-range, and they are able to infect and replicate in cats, causing diseases indistinguishable from feline panleukopenia. Furthermore, as cats are susceptible to both CPV-2 and FPV viruses, superinfection and co-infection with multiple parvovirus strains may occur, potentially facilitating recombination and high genetic heterogeneity. In the light of the importance of cats as a potential source of genetic diversity for parvoviruses and, since feline panleukopenia virus has re-emerged as a major cause of mortality in felines, the present study has explored the molecular characteristics of parvovirus strains circulating in cat populations. The most significant findings reported in this study were (a) the detection of mixed infection FPV/CPV with the presence of one parvovirus variant which is a true intermediate between FPV/CPV and (b) the quasispecies cloud size of one CPV sample variant 2c. In conclusion, this study provides new important results about the evolutionary dynamics of CPV infections in cats, showing that CPV has presumably started a new process of readaptation in feline hosts