Social Dimension and Work with the families of AIDS Patients and Carriers

The family constitutes a small social group. Each problem and each experience of one of its members touches theothers in the group. Namely, there is a form of constant interaction among the members, which is intensified byinternal and external factors. For situations that the family members classify as low in importance, temporary andcontrolled, their resolution process as well as any cost is manageable. Therefore, reactions are, most of the time,quite limited. What happens though with serious multi-factor impact situations, especially non reversible ones, suchas illnesses? What is the reaction of the family members in cases of terminal illnesses, which are also related to thesensitive issue of a person’s sexuality? Every professional in health, welfare and rehabilitation services will facethese questions and situations in his direct or indirect involvement with the members of the patient’s family, in hiseffort to properly accomplish his task

ATLAS Detector Commissioning with Photons

An intense commissioning activity of the ATLAS detector has preceded the LHC beam start up. Both cosmics events and in earlier periods test beam events have been utilized. The commission- ing of the ATLAS detector using photons has been an integral part of this effort. In this paper we present the results of these activities following a discussion of the reconstruction of photons in the ATLAS detector

Sensitive cells: Enabling tools for static and dynamic control of microbial pathways

For the purpose of reprogramming the cellular network we employ in silico model of the genome-wide metabolism in order to predict genetic modifications that lead to increases in carbon fluxes of interest. Such Systems Biology approaches, in combination with traditional genetic engineering have resulted in robust production levels that can result in the commercially viable processes for the synthesis of important molecules. In addition to such approaches, we will also describe the engineering of both positive and negative feedback controls for dynamic tuning of metabolic flux around intracellular metabolites, such as malonyl-CoA in microorganisms using a dual transcriptional regulator. We will also demonstrate that such dynamic regulation can also be accomplished through the construction of orthogonal variants of the classic T7lac promoter using site-directed mutagenesis, generating a panel of inducible hybrid promoters regulated by both LacI and dCas9 and covering a wide expression range. Remarkably, dCas9 orthogonality in our system is mediated by only 23 nucleotide mismatches in a narrow window of the RNA:DNA hybrid, neighboring the protospacer adjacent motif (PAM). Finally, the presentation will also cover our work on the development and optimization of polycultures (three or more strains in co-culture) for the extension of recombinant pathways, such as the flavonoid branch pathway, in vivo. This technology has enabled, for the first time, the de novo production of flavan-3-ols and anthocyanins in E. coli. Utilizing a computationally guided optimization approach, we were able to demonstrate up to a 970-fold improvement over previously published monoculture titer

An application of Doppler echocardiography and tissue Doppler Imaging in the evacuation of cardiac function of normal cats and cats with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) of cats is the most common cardiac disease of this species. Feline HCM shares many of the morphological characteristics recorded with human HCM. Diastolic impairment is believed to be the main abnormality of the disease and evidence for this has been provided by both invasive and Doppler echocardiography studies. Tissue Doppler Imaging (TDI) has emerged in the last decade as an alternative tool for the non-invasive quantification of regional and global myocardial function. TDI studies in affected humans and experimental animals have shown that systolic impairment is also evident in HCM, despite the presence of normal or supernormal contractile state of the LV in this cardiac entity.The aims of this study were (1) to produce Doppler echocardiographic criteria of normality in cats; (2) to identify differences in ventricular function using Doppler echocardiography between normal cats and cats with HCM; (3) to investigate diastolic and systolic function in normal cats and cats with HCM, by means of TDI.There was no significant difference in LV FS% between normal and HCM cats although affected cats tended to have higher FS%. Apart from the E deceleration time of mitral inflow, which was prolonged in HCM cats, neither the E/A of mitral inflow nor the FVRT were different between the two groups. The LV flow propagation velocity was significantly lower in the affected group compared to that in normal. Asymptomatic affected cats had a higher S wave and S/D ratio and a lower D wave of pulmonary venous flow (PVF) than normal cats. The time from the Q wave of the ECG to peak systolic velocities of PVF was significantly prolonged in the HCM than in the normal group. HCM cats showed significantly higher aortic and pulmonic velocities than normal cats.The TDI technique revealed evidence of both diastolic and systolic dysfunction in HCM cats. On pulsed TDI data, diastolic dysfunction was expressed with decreased early diastolic velocities, lower early diastolic acceleration and deceleration, prolonged IVRt and decreased E'/A', mainly along the longitudinal axis of the heart. The physiologic time and space non-uniformity recorded in the LV motion of normal cats was lost in affected cats. Systolic dysfunction in the HCM group was less prominent than the diastolic, and was expressed with decreased late systolic velocities and systolic acceleration mainly along the longitudinal axis. This decrease was independent from left ventricular out-flow tract obstruction and was present in asymptomatic affected cats. Cats with CHF showed a tendency for decreased systolic myocardial indices. On colour M-mode TDI, certain colour velocity stripes were appeared on the LVPW of cats and were corresponded to certain peaks occurring in tracings of both the Myocardial Velocity Gradients (MVG) and Mean Myocardial Velocity (MMV). Biphasic shifts were recorded in the LVPW during early diastole and the two isovolumic periods. MVG followed wall thickness changes during the different phases of the cardiac cycle. Peak MVG during early diastole and systole was significantly reduced in HCM cats compared to that in normals. Peak MMV during the second phase of the isovolumic contraction period was significantly reduced in HCM catsThis study, for the first time, offers evidence for systolic dysfunction in feline HCM. The data presented here provide reference data for future studies in the investigation and better classification of feline cardiac diseases. The successful application of TDI in cats, despite the very small size of their heart and the inherent high heart rates often encountered in this species, provides evidence for possible successful application of the technique in human neonatal hearts and experimental small animal models of human diseases

Going In Style: Audio Backdoors Through Stylistic Transformations

This work explores stylistic triggers for backdoor attacks in the audio domain: dynamic transformations of malicious samples through guitar effects. We first formalize stylistic triggers - currently missing in the literature. Second, we explore how to develop stylistic triggers in the audio domain by proposing JingleBack. Our experiments confirm the effectiveness of the attack, achieving a 96% attack success rate. Our code is available in https://github.com/skoffas/going-in-style.Comment: Accepted to ICASSP '23 and the first two authors contributed equall

Biosynthesis of isoprenoids, polyunsaturated fatty acids and flavonoids in Saccharomyces cerevisiae

Industrial biotechnology employs the controlled use of microorganisms for the production of synthetic chemicals or simple biomass that can further be used in a diverse array of applications that span the pharmaceutical, chemical and nutraceutical industries. Recent advances in metagenomics and in the incorporation of entire biosynthetic pathways into Saccharomyces cerevisiae have greatly expanded both the fitness and the repertoire of biochemicals that can be synthesized from this popular microorganism. Further, the availability of the S. cerevisiae entire genome sequence allows the application of systems biology approaches for improving its enormous biosynthetic potential. In this review, we will describe some of the efforts on using S. cerevisiae as a cell factory for the biosynthesis of high-value natural products that belong to the families of isoprenoids, flavonoids and long chain polyunsaturated fatty acids. As natural products are increasingly becoming the center of attention of the pharmaceutical and nutraceutical industries, the use of S. cerevisiae for their production is only expected to expand in the future, further allowing the biosynthesis of novel molecular structures with unique properties

When plants produce not enough or at all: metabolic engineering of flavonoids in microbial hosts

As a result of the discovery that flavonoids are directly or indirectly connected to health, flavonoid metabolism and its fascinating molecules that are natural products in plants, have attracted the attention of both the industry and researchers involved in plant science, nutrition, bio/chemistry, chemical bioengineering, pharmacy, medicine, etc. Subsequently, in the past few years, flavonoids became a top story in the pharmaceutical industry, which is continually seeking novel ways to produce safe and efficient drugs. Microbial cell cultures can act as workhorse bio-factories by offering their metabolic machinery for the purpose of optimizing the conditions and increasing the productivity of a selective flavonoid. Furthermore, metabolic engineering methodology is used to reinforce what nature does best by correcting the inadequacies and dead-ends of a metabolic pathway. Combinatorial biosynthesis techniques led to the discovery of novel ways of producing natural and even unnatural plant flavonoids, while, in addition, metabolic engineering provided the industry with the opportunity to invest in synthetic biology in order to overcome the currently existing restricted diversification and productivity issues in synthetic chemistry protocols. In this review, is presented an update on the rationalized approaches to the production of natural or unnatural flavonoids through biotechnology, analyzing the significance of combinatorial biosynthesis of agricultural/pharmaceutical compounds produced in heterologous organisms. Also mentioned are strategies and achievements that have so far thrived in the area of synthetic biology, with an emphasis on metabolic engineering targeting the cellular optimization of microorganisms and plants that produce flavonoids, while stressing the advances in flux dynamic control and optimization. Finally, the involvement of the rapidly increasing numbers of assembled genomes that contribute to the gene- or pathway-mining in order to identify the gene(s) responsible for producing species-specific secondary metabolites is also considered herein.National Strategic Reference Framework. THALES-TEI CRETE, MIS 380210 Progra

Early Treatment Consideration in Patients with Hepatitis B 'e' Antigen-Positive Chronic Infection: Is It Time for a Paradigm Shift?

Chronic hepatitis B (CHB) is associated with significant morbidity and mortality, due to the adverse sequelae of cirrhosis and hepatocellular carcinoma (HCC). To date, antiviral therapy has been reserved for patients with ostensibly active liver disease, fibrosis or cirrhosis, and/or increased risk of HCC. Historically, patients with hepatitis B ‘e’ antigen (HBeAg)-positive chronic infection, were not offered antiviral therapy. Nevertheless, there has been compelling evidence emerging in recent years, demonstrating that this disease phase is in fact not characterized by immunological tolerance. HBV integration into the human genome is a frequent event found in these patients. Additionally, it may well be associated with active inflammation and fibrosis, even in the presence of persistently normal liver enzymes. Likewise, it appears that the mechanisms of hepatocarcinogenesis are already present during this early stage of the disease. This was reflected in the European Association for the Study of the Liver (EASL) guidelines, where treating patients above the age of 30 years with HBeAg-positive chronic infection was proposed. Lowering the treatment threshold to broaden treatment eligibility is likely to slow disease progression and reduce the risk of developing HCC. The current review discusses the reasons to consider early antiviral therapy in HBeAg-positive chronic infection