Studying, designing and 3d-printing an operational model of the Antikythera Mechanism

3D printing technology is an established industrial practice for rapid prototyping and manufacturing across a range of products, components and commercial sectors and at the same time possesses great potential for every-day life applications to be invented, explored and developed by the coming generations of scientists and engineers. A 3D printer installed in a school setting and complemented by well-designed educational activities can: stimulate the interest and curiosity of students; engage and motivate them into studying science, technology, engineering and mathematics (STEM) subjects, that they may choose or consider as career options; give the opportunity to teachers to achieve content and concept learning in an innovative way. In this paper we present an interdisciplinary science course that was developed for high school students and was implemented in an actual science classroom. The objectives of the course were both to spark the interest and creativity of students and teach them certain curriculum units the content knowledge of which is reached or utilized in an unconventional way. Students are gradually introduced into the 3D printing technology, its application and potential and are assigned a challenging collaborative project in which they have to study, analyse, design and build, using the 3D printer of their school, an operational model of a renown ancient artefact, the so-called Antikythera Mechanism. The mechanism is a 2100-year-old computer and is internationally known as an artefact of unprecedented human ingenuity and scientific, historic and symbolic value. The course involves the teaching of STEM curriculum domains of physics, astronomy, mathematics/geometry, informatics and technology related content and also non-STEM subjects like history and Greek language, both ancient and modern. We give an overview of the course, discuss its various phases and highlight its outcomes

Exercise tolerance and quality of life in patients with known or suspected coronary artery disease

Background: Coronary artery disease (CAD) is known to impact on patients’ physical and mental health. The relationship between performance on treadmill exercise tolerance test (ETT) and health-related quality of life (HRQL)has never been specifically investigated in the setting of CAD. Methods: Consecutive patients undergoing an ETT with the Bruce protocol during a diagnostic workup for CAD (n = 1,631, age 55 ± 12 years) were evaluated. Exercise-related indices were recorded. Detailed information on cardiovascular risk factors and past medical history were obtained. HRQLwas assessed with the use of the validated 36-Item Short Form Survey (SF-36) questionnaire. Results: Increasing age and the presence of cardiovascular risk factors and comorbidities correlated with lower scores on the physical and mental health component of SF-36(all P < 0.05). Subjects with arrhythmias during exercise and slow recovery of systolic blood pressure had lower scores on the physical health indices or the Social Role Functioning component (P < 0.05). Achieved target heart rate and good exercise tolerance were independently associated with better scores of the physical and mental health domains of SF-36 and overall HRQLscores (β = 0.05 for target HR and PCS-36, β = 1.86 and β = 1.66 per increasing stage of exercise tolerance and PCS-36 and MCS-36, respectively, P < 0.001 for all associations). Ischemic ECG changes were associated with worse scores on Physical Functioning (β = − 3.2, P = 0.02) and Bodily Pain (β = − 4.55, P = 0.026). Conclusion: ETT parameters are associated with HRQL indices in patients evaluated for possible CAD. Physical conditioning may increase patient well-being and could serve as a complementary target in conjunction with cardiovascular drug therapy

Tiny Rare-Earth Fluoride Nanoparticles Activate Tumour Cell Growth via Electrical Polar Interactions

© 2018, The Author(s). Localised extracellular interactions between nanoparticles and transmembrane signal receptors may well activate cancer cell growth. Herein, tiny LaF3 and PrF3 nanoparticles in DMEM+FBS suspensions stimulated tumour cell growth in three different human cell lines (A549, SW837 and MCF7). Size distribution of nanoparticles, activation of AKT and ERK signalling pathways and viability tests pointed to mechanical stimulation of ligand adhesion binding sites of integrins and EGFR via a synergistic action of an ensemble of tiny size nanoparticles (< 10 nm). While tiny size nanoparticles may be well associated with the activation of EGFR, integrin interplay with nanoparticles remains a multifaceted issue. A theoretical motif shows that, within the requisite pN force scale, each ligand adhesion binding site can be activated by a tiny size dielectric nanoparticle via electrical dipole interaction. The size of the active nanoparticle stayed specified by the amount of the surface charges on the ligand adhesion binding site and the nanoparticle, and also by the separating distance between them. The polar component of the electrical dipole force remained inversely proportional to the second power of nanoparticle’s size, evincing that only tiny size dielectric nanoparticles might stimulate cancer cell growth via electrical dipole interactions. The work contributes towards recognising different cytoskeletal stressing modes of cancer cells

The Hellenic type of nondeletional hereditary persistence of fetal hemoglobin results from a novel mutation (g.-109G>T) in the HBG2 gene promoter

Nondeletional hereditary persistence of fetal hemoglobin (nd-HPFH), a rare hereditary condition resulting in elevated levels of fetal hemoglobin (Hb F) in adults, is associated with promoter mutations in the human fetal globin (HBG1 and HBG2) genes. In this paper, we report a novel type of nd-HPFH due to a HBG2 gene promoter mutation (HBG2:g.-109G>T). This mutation, located at the 3′ end of the HBG2 distal CCAAT box, was initially identified in an adult female subject of Central Greek origin and results in elevated Hb F levels (4.1%) and significantly increased Gγ-globin chain production (79.2%). Family studies and DNA analysis revealed that the HBG2:g.-109G>T mutation is also found in the family members in compound heterozygosity with the HBG2:g.-158C>T single nucleotide polymorphism or the silent HBB:g.-101C>T β-thalassemia mutation, resulting in the latter case in significantly elevated Hb F levels (14.3%). Electrophoretic mobility shift analysis revealed that the HBG2:g.-109G>T mutation abolishes a transcription factor binding site, consistent with previous observations using DNA footprinting analysis, suggesting that guanine at position HBG2/1:g.-109 is critical for NF-E3 binding. These data suggest that the HBG2:g-109G>T mutation has a functional role in increasing HBG2 transcription and is responsible for the HPFH phenotype observed in our index cases

Institutional Profile: Golden Helix Institute of Biomedical Research: interdisciplinary research and educational activities in pharmacogenomics and personalized medicine

The Golden Helix Institute of Biomedical Research is an international non-profit scientific organization with interdisciplinary research and educational activities in the field of genome medicine in Europe, Asia and Latin America. These activities are supervised by an international scientific advisory council, consisting of world leaders in the field of genomics and translational medicine. Research activities include the regional coordination of the Pharmacogenomics for Every Nation Initiative in Europe, in an effort to integrate pharmacogenomics in developing countries, the development of several National/Ethnic Genetic databases and related web services and the critical assessment of the impact of genetics and genomic medicine to society in various countries. Also, educational activities include the organization of the Golden Helix Symposia®, which are high profile scientific research symposia in the field of personalized medicine, and the Golden Helix Pharmacogenomics Days, an international educational activity focused on pharmacogenomics, as part of its international pharmacogenomics education and outreach efforts

Nanothermodynamics mediates drug delivery

© Springer International Publishing Switzerland 2015. The efficiency of penetration of nanodrugs through cell membranes imposes further complexity due to nanothermodynamic and entropic potentials at interfaces. Action of nanodrugs is effective after cell membrane penetration. Contrary to diffusion of water diluted common molecular drugs, nanosize imposes an increasing transport complexity at boundaries and interfaces (e.g., cell membrane). Indeed, tiny dimensional systems brought the concept of “nanothermodynamic potential,” which is proportional to the number of nanoentities in a macroscopic system, from either the presence of surface and edge effects at the boundaries of nanoentities or the restriction of the translational and rotational degrees of freedom of molecules within them. The core element of nanothermodynamic theory is based on the assumption that the contribution of a nanosize ensemble to the free energy of a macroscopic system has its origin at the excess interaction energy between the nanostructured entities. As the size of a system is increasing, the contribution of the nanothermodynamic potential to the free energy of the system becomes negligible. Furthermore, concentration gradients at boundaries, morphological distribution of nanoentities, and restriction of the translational motion from trapping sites are the source of strong entropic potentials at the interfaces. It is evident therefore that nanothermodynamic and entropic potentials either prevent or allow enhanced concentration very close to interfaces and thus strongly modulate nanoparticle penetration within the intracellular region. In this work, it is shown that nano-sized polynuclear iron (III)-hydroxide in sucrose nanoparticles have a nonuniform concentration around the cell membrane of macrophages in vivo, compared to uniform concentration at hydrophobic prototype surfaces. The difference is attributed to the presence of entropic and nanothermodynamic potentials at interfaces

Selective aggregation of PAMAM dendrimer nanocarriers and PAMAM/ZnPc nanodrugs on human atheromatous carotid tissues: a photodynamic therapy for atherosclerosis

© 2015, Spyropoulos-Antonakakis et al.; licensee Springer. Photodynamic therapy (PDT) involves the action of photons on photosensitive molecules, where atomic oxygen or OH− molecular species are locally released on pathogenic human cells, which are mainly carcinogenic, thus causing cell necrosis. The efficacy of PDT depends on the local nanothermodynamic conditions near the cell/nanodrug system that control both the level of intracellular translocation of nanoparticles in the pathogenic cell and their agglomeration on the cell membrane. Dendrimers are considered one of the most effective and promising drug carriers because of their relatively low toxicity and negligible activation of complementary reactions. Polyamidoamine (PAMAM) dendrite delivery of PDT agents has been investigated in the last few years for tumour selectivity, retention, pharmacokinetics and water solubility. Nevertheless, their use as drug carriers of photosensitizing molecules in PDT for cardiovascular disease, targeting the selective necrosis of macrophage cells responsible for atheromatous plaque growth, has never been investigated. Furthermore, the level of aggregation, translocation and nanodrug delivery efficacy of PAMAM dendrimers or PAMAM/zinc phthalocyanine (ZnPc) conjugates on human atheromatous tissue and endothelial cells is still unknown. In this work, the aggregation of PAMAM zero generation dendrimers (G0) acting as drug delivery carriers, as well as conjugated G0 PAMAM dendrimers with a ZnPc photosensitizer, to symptomatic and asymptomatic human carotid tissues was investigated by using atomic force microscopy (AFM). For the evaluation of the texture characteristics of the AFM images, statistical surface morphological and fractal analytical methodologies and Minkowski functionals were used. All statistical quantities showed that the deposition of nanodrug carriers on healthy tissue has an inverse impact when comparing to the deposition on atheromatous tissue with different aggregation features between G0 and G0/ZnPc nanoparticles and with considerably larger G0/ZnPc aggregations on the atheromatous plaque. The results highlight the importance of using PAMAM dendrimer carriers as a novel and promising PDT platform for atherosclerosis therapies

A critical view of the general public's awareness and physicians' opinion of the trends and potential pitfalls of genetic testing in Greece

Aim: Progress in deciphering the functionality of the human genome sequence in the wake of technological advances in the field of genomic medicine have dramatically reduced the overall costs of genetic analysis, thereby facilitating the incorporation of genetic testing services into mainstream clinical practice. Although Greek genetic testing laboratories offer a variety of different genetic tests, relatively little is known about how either the general public or medical practitioners perceive genetic testing services. Materials & methods: We have therefore performed a nationwide survey of the views of 1717 members of the general public, divided into three age groups, from all over Greece, and residing in both large and small cities and villages, in order to acquire a better understanding of how they perceive genetic testing. We also canvassed the opinions of 496 medical practitioners with regard to genetic testing services in a separate survey that addressed similar issues. Results: Our subsequent analysis indicated that a large proportion of the general public is aware of the nature of DNA, genetic disorders and the potential benefits of genetic testing, although this proportion declines steadily with age. Furthermore, a large proportion of the interviewed individuals would be willing to undergo genetic testing even if the cost of analysis was not covered by healthcare insurance. However, a relatively small proportion of the general public has actually been advized to undergo genetic testing, either by relatives or physicians. Most physicians believe that the regulatory and legal framework that governs genetic testing services in Greece is rather weak. Interestingly, the vast majority of the general public strongly opposes direct-access genetic testing, and most would prefer referral from a physician than from a pharmacist. Conclusion: Overall, our results provide a critical evaluation of the views of the general public with regard to genetics and genetic testing services in Greece and should serve as a model for replication in other populations

Differentially expressed genes in a flock of Chinese local-breed chickens infected with a subgroup J avian leukosis virus using suppression subtractive hybridization

Avian leukosis virus subgroup J (ALV-J) is a new type of virus that mainly induces myeloid leukosis (ML) in chickens. To further elucidate the pathogenesis of ALV-J infection and tumor development, expression profiles from the bone marrow tissue of 15 infected and 18 non-infected birds from a local-breed poultry-farm under naturally infected conditions, were analyzed by suppression-subtractive hybridization. The birds were diagnosed as ML+ (or ML-) by specific ALV-J detection methods, involving serological tests for antigens and antibodies, and RT-PCR to detect viral RNA. A total of 59 partial gene sequences were revealed by differential screening of 496 forward and 384 reverse subtracted cDNA clones. Of these, 22 identified genes, including 8 up-regulated and 14 down-regulated, were related to immune functions, these genes being, MHC B-G antigen, translationally-controlled tumor protein (TPT1/TPTC), transferrin and ferritin, hemoglobin and Carbonic anhydrase. Four of the down-regulated genes were selected for further analysis, in view of their predicted roles in infection and immunity by real-time qRT-PCR, using RNA collected from the same birds as those used for SSH. The four genes were expressed at significantly lower levels (p < 0.001) in ALV-J infected birds than in non-infected ones