Human Cloning for Personal Gain

Most students in their grade school career have learned about Dolly the cloned sheep. While this process was a scientific endeavor, would cloning humans be for the same purpose as Dolly or for personal gain? Whatever the answer may be, most people have their own agenda behind their acts of human cloning which range from a variety of desires. The most common begin with trying to suffice with personal loss to attempting to advance science. Every reasoning is different, but both rely on this process to accomplish their goals. My research will include many academic journals, films, and literature to explain the current society’s interests in pursuing human cloning to suffice personal loss. In my presentation, I will be focusing on the scientific process of cloning, and different case studies about this topic. Human cloning appeals to those who want to have eternal life as well as an eternal life for a loved one, save a dying person, and bring someone back from the dead.This topic contributes to the presentation because it introduces the process of cloning, and shows how personal gain is more popular amongst today’s society than furthering our knowledge on the limits of cloning. I hope to appeal to the audience that does not know much about cloning, but also to activists who have a desire to make cloning legal, which includes the general public

pH Regulatory Molecules In The Tumour Microenvironment: Modulators Of Aggressiveness And Immune Profile Of Human Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) arises in an inflammatory, hypoxic/acidic microenvironment that favours tumour progression and fosters immunosuppression. Tumour cells survive this hostile environment by over-expressing pH regulatory molecules such as carbonic anhydrase (CA) IX, XII and V-ATPase complex, but the relevance of these molecules in HCC is poorly defined. Aim: The aim of this study was to dissect the relationships between pH regulatory molecules and the aggressive behaviour of malignant hepatocytes, and to evaluate how pH regulatory molecules influence the immune microenvironment of HCC. Methods: HCC, non-tumour and normal liver tissue samples were analysed by qRT-PCR for the expression of genes encoding the pH regulatory molecules (CAIX, CAXII and V-ATPase), of genes associated to epithelial-to-mesenchymal-transition (EMT) (TWIST, CDH1, VIM) and those encoding for HCC stem cell-associated markers (CD13, CD24, CD44, CD90, EpCAM, CD133, KRT19, OCT4, NANOG and SOX2). Selected HCC, non-tumour and normal liver tissue samples were evaluated by immunohistochemistry (IHC) to detect the presence and localization of CAIX, CAXII and VATPase and to assess the distribution of macrophages and T cells. Confocal microscopy and flow cytometry were implemented to assess the co-expression of selected markers. HCC cell lines, characterised for the expression of pH regulators, were tested for the sensitivity to the CAIX, CAXII, and V-ATPase specific inhibitors. The effects of V-ATPase specific drug were also studied ex vivo in primary human HCC tumour explants by qRT-PCR and by flow cytometry in HCC single cell suspensions obtained by the enzymatic digestion of HCC specimens. Results: Our mRNA analysis showed that the expression of CA9 was significantly correlated with the expression of the hypoxia-inducible factor 1α-related gene (HIF1A) and of the stem cell-associated markers CD24, CD133, EpCAM and KRT19. Moreover, mRNA for CA9 and for the different CA12 isoforms were associated with tumour grading, thus indicating their possible role in tumour malignancy. Applying a machine learning tool known as the ‘Adaptive Index Model’ the combined expression of different CA12 isoforms, CD209 and CDH1 defined a ‘signature’ classifying HCC patients in groups at different risk of recurrence, thus indicating a link between pH regulators, myeloid and EMT markers likely influencing HCC prognosis. IHC analysis indicated that HCC displays a complex expression pattern for the pH regulatory proteins. Both CAIX and CAXII were detected in transformed, but not in normal hepatocytes. CAIX protein had a focal distribution in the tumour, thus supporting its possible association with hypoxic and the most aggressive tumour area. Conversely, CAXII was homogeneously expressed by all tumour hepatocytes, but mainly retained in the endoplasmic reticulum (ER). The majority of HCC expressed V-ATPase which, importantly, was also present in immune infiltrating cells. This expression pattern qualified the CAIX, CAXII and V-ATPase as possible targetable molecules. Our in vitro data indicated that blockage of their enzymatic activities by specific drugs affected the viability of HCC cell lines in a dose dependent fashion, although with the CAXII specific inhibitor showing low efficacy, likely related to the preferential ER localization of CAXII molecules inside the HCC cells. Ex vivo experiments with HCC tissue explants and HCC cellular suspensions showed that inhibition of VATPase modulated the epithelial/mesenchymal features of HCC cells and the levels of pro- and anti-tumour cytokines expressed by M2 macrophages and T cells infiltrating HCC. Conclusions: Herein, our data demonstrated that the pH regulatory molecules, CAIX, CAXII and V-ATPase are over expressed in the HCC microenvironment and interfering with their pathways exerted anti-tumour activities, although these data also lead to the conclusion that more effective CAXII specific drugs should be designed. The results of this thesis also suggest that pH regulatory molecules might have a role in HCC aggressiveness and prognosis. Importantly, one of these pH regulators, namely V-ATPase complex, influences the mesenchymal features of tumour cells and the immunosuppressive tumour microenvironment (TME). Interfering with tumour metabolism is an emerging strategy for treating cancers that are resistant to standard therapies. Thus, targeting the unique crosstalk between tumour cells and the microenvironment, played by the pH regulatory molecules, can be considered as a new option for HCC treatment and the blockage of the V-ATPase complex might represent a multi-task strategy for the treatment of HCC patients

Horizontal and Vertical BIM Interoperability Aimed at Seismic Vulnerability Assessment

A vital task of this millennium is to protect the existing heritage, also through the adoption of resilient management systems. In this framework, the organization of knowledge remains one of the critical points. For this reason, new methodologies and cross-disciplinary technologies are increasingly being chosen to optimize resources toward more sustainable interventions. Therefore, the ability to model the building geometry and behavior must be maximized through interoperable processes between Building Information Modeling and Finite Element Modeling methods aimed at the seismic vulnerability assessment. Setting up an integrated digitalization process is undoubtedly challenging initially but returns more significant benefits during the infrastructure life cycle. The interoperability tests' bi-directionality is essential for constantly evaluating activities to update data following facilities' modifications. The Modal Assurance Criterion indicator is used to assess the coherence of the models after possible simplifications introduced for non-linear state analyses

Carbon Quantum Dots from Lemon Waste Enable Communication among Biodevices

A bioinspired method of communication among biodevices based on fluorescent nanoparticles is herein presented. This approach does not use electromagnetic waves but rather the exchange of chemical systems—a method known as molecular communication. The example outlined was based on the fluorescence properties of carbon dots and follows a circular economy approach as the method involves preparation from the juice of lemon waste. The synthesis is herein presented, and the fluorescence properties and diffusion coefficient are evaluated. The application of carbon dots to molecular communication was studied from a theoretical point of view by numerically solving the differential equation that governs the phenomenon. The theoretical results were used to develop a prototype molecular communication platform that enables the communication of simple messages via aqueous fluids to a fluorescence-detecting biodevice receiver

Functionalized Carbon Nanoparticle-Based Sensors for Chemical Warfare Agents

Real-time sensing of chemical warfare agents (CWAs) is, today, a crucial topic to prevent lethal effects of a chemical terroristic attack. For this reason, the development of efficient, selective, ..

Cancer acidity: An ultimate frontier of tumor immune escape and a novel target of immunomodulation

The link between cancer metabolism and immunosuppression, inflammation and immune escape has generated major interest in investigating the effects of low pH on tumor immunity. Indeed, microenvironmental acidity may differentially impact on diverse components of tumor immune surveillance, eventually contributing to immune escape and cancer progression. Although the molecular pathways underlying acidity-related immune dysfunctions are just emerging, initial evidence indicates that antitumor effectors such as T and NK cells tend to lose their function and undergo a state of mostly reversible anergy followed by apoptosis, when exposed to low pH environment. At opposite, immunosuppressive components such as myeloid cells and regulatory T cells are engaged by tumor acidity to sustain tumor growth while blocking antitumor immune responses. Local acidity could also profoundly influence bioactivity and distribution of antibodies, thus potentially interfering with the clinical efficacy of therapeutic antibodies including immune checkpoint inhibitors. Hence tumor acidity is a central regulator of cancer immunity that orchestrates both local and systemic immunosuppression and that may offer a broad panel of therapeutic targets. This review outlines the fundamental pathways of acidity-driven immune dysfunctions and sheds light on the potential strategies that could be envisaged to potentiate immune-mediated tumor control in cancer patients

Carbon Quantum Dots as Fluorescence Nanochemosensors for Selective Detection of Amino Acids

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Evidence for a hopping mechanism in metal|single molecule|metal junctions involving conjugated metal–terpyridyl complexes; potential-dependent conductances of complexes [M(pyterpy)₂] ²⁺ (M = Co and Fe; pyterpy = 4′-(pyridin-4-yl)-2,2′:6′,2′′-terpyridine) in ionic liquid

Extensive studies of various families of conjugated molecules in metal|molecule|metal junctions suggest that the mechanism of conductance is usually tunnelling for molecular lengths < ca. 4 nm, and that for longer molecules, coherence is lost as a hopping element becomes more significant. In this work we present evidence that, for a family of conjugated, redox-active metal complexes, hopping may be a significant factor for even the shortest molecule studied (ca. 1 nm between contact atoms). The length dependence of conductance for two series of such complexes which differ essentially in the number of conjugated 1,4-C₆H₄- rings in the structures has been studied, and it is found that the junction conductances vary linearly with molecular length, consistent with a hopping mechanism, whereas there is significant deviation from linearity in plots of log(conductance) vs. length that would be characteristic of tunnelling, and the slopes of the log(conductance)–length plots are much smaller than expected for an oligophenyl system. Moreover, the conductances of molecular junctions involving the redox–active molecules, [M(pyterpy)₂] ²⁺/³⁺ (M = Co, Fe) have been studied as a function of electrochemical potential in ionic liquid electrolyte, and the conductance–overpotential relationship is found to fit well with the Kuznetsov–Ulstrup relationship, which is essentially a hopping description