Modeling and spatial visualization of indoor micro-climates for personalized thermal comfort

The indoor thermal environment is conventionally considered homogeneous as anchored on a universal thermal comfort paradigm, although occupants’ experience is often diversified and influenced by several physio-cognitive factors. Personal comfort devices aim to enhance thermal comfort acceptance through localized heating and cooling while reducing overall energy consumption as temperature set-points of centralized HVAC systems can be relaxed. To further incentivize the adoption of distributed HVAC systems, it is critical to examine the energy benefits and the spatial characteristics of heterogeneous thermal environments. Here we developed a parametric framework based on building energy modeling coupled with a spatial visualization of micro-climatic thermal fields, which respond to a variable space occupation. HVAC system loads and indoor environmental conditions, extracted from the energy model, are integrated with an analysis of the human thermal balance. As a case study, a thermoelectric-based system for personalized thermal comfort was considered in an office space, based on a specific layout of workstations and meeting rooms. The contribution of distributed heating and cooling systems to the overall HVAC energy consumption was analyzed for the office, and the micro-climatic variability was visualized based on transient occupation patterns. Understanding the impact of variable occupation for the building energy balance is significant for developing performative metrics for next-generation distributed HVAC systems. At the same time, it can inform novel design strategies based on micro-climatic controls to maximize personalized thermal comfort and enhance the quality of indoor environments

Metabolization of [Ru(η6-C6H5CF3)(pta)Cl2]: a cytotoxic RAPTA-type complex with a strongly electron withdrawing arene ligand

The anticancer ruthenium-arene compound [Ru(η6-C6H5CF3)(pta)Cl2] (where pta is 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane), termed RAPTA-CF3, with the electron-withdrawing α,α,α-trifluorotoluene ligand, is one of the most cytotoxic RAPTA compounds known. To rationalize the high observed cytotoxicity, the hydrolysis of RAPTA-CF3 in water and brine (100mM sodium chloride) and its reactions with the protein ubiquitin and a double-stranded oligonucleotide (5′-GTATTGGCACGTA-3′) were studied using NMR spectroscopy, high-resolution Fourier transform ion cyclotron resonance mass spectrometry, and gel electrophoresis. The aquation of the ruthenium-chlorido complex was accompanied by a loss of the arene ligand, independent of the chloride concentration, which is a special property of the compound not observed for other ruthenium-arene complexes with relatively stable ruthenium-arene bonds. Accordingly, the mass spectra of the biomolecule reaction mixtures contained mostly [Ru(pta)]-biomolecule adducts, whereas [Ru(pta)(arene)] adducts typical of other RAPTA compounds were not observed in the protein or DNA binding studies. Gel electrophoresis experiments revealed a significant degree of decomposition of the oligonucleotide, which was more pronounced in the case of RAPTA-CF3 compared with RAPTA-C. Consequently, facile arene loss appears to be responsible for the increased cytotoxicity of RAPTA-CF3. Graphical abstract: RAPTA-CF3 is a fast-acting cytotoxic compound that degrades DNA and has a mode of action fundamentally different from that of other ruthenium(II)-arene compound

Synthesis and Anticancer Activity of Long-Chain Isonicotinic Ester Ligand-Containing Arene Ruthenium Complexes and Nanoparticles

Arene ruthenium complexes containing long-chain N-ligands L1=NC5H4-4-COO-C6H4-4-O-(CH2)9-CH3 or L2=NC5H4-4-COO-(CH2)10-O-C6H4-4-COO-C6H4-4-C6H4-4-CN derived from isonicotinic acid, of the type [(arene)Ru(L)Cl2] (arene=C6H6, L=L1: 1; arene=p-MeC6H4Pri, L=L1: 2; arene=C6Me6, L=L1: 3; arene=C6H6, L=L2: 4; arene=p-MeC6H4Pri, L=L2: 5; arene=C6Me6, L=L2: 6) have been synthesized from the corresponding [(arene)RuCl2]2 precursor with the long-chain N-ligand L in dichloromethane. Ruthenium nanoparticles stabilized by L1 have been prepared by the solvent-free reduction of 1 with hydrogen or by reducing [(arene)Ru(H2O)3]SO4 in ethanol in the presence of L1 with hydrogen. These complexes and nanoparticles show a high anticancer activity towards human ovarian cell lines, the highest cytotoxicity being obtained for complex 2 (IC50=2μM for A2780 and 7μM for A2780cisR

Do You Speak Cyber?:Talking Security with Developers of Health Systems and Devices

Security and privacy concerns are vital in software for health-related applications. Yet often their development teams in small companies have little professional security support. To work effectively with them we should accept the complexity of their decision-making, create stories as a basis for discussion, and use different jargon from cyber-professionals

HIPSTER Project - State of the Art:Technical Report

Health IoT (HIoT) software offers thorny and complex security, privacy and safeguarding (SPS) problems and requirements, with huge potential impact. The HIPSTER project aims to help development teams in the Small-to-Medium Enterprise community, incorporating background information from cyber threat and risk intelligence to create a cost-effective intervention to support decision making around such threats and requirements. This report outlines the approach we plan to use and explores the academic ‘state of the art’ literature around the project. It concludes that the areas of novelty for the project are in finding ways to make risk data meaningful and palatable for software development teams; and in finding objective sources of such security and privacy information for this domain. To support readers in using the literature referenced, all citations and bibliography entries in this document have hyperlinks to the corresponding sources

Enhanced bacterial cancer therapy delivering therapeutic RNA interference of c-Myc

BackgroundBacterial cancer therapy was first trialled in patients at the end of the nineteenth century. More recently, tumour-targeting bacteria have been harnessed to deliver plasmid-expressed therapeutic interfering RNA to a range of solid tumours. A major limitation to clinical translation of this is the short-term nature of RNA interference in vivo due to plasmid instability. To overcome this, we sought to develop tumour-targeting attenuated bacteria that stably express shRNA by virtue of integration of an expression cassette within the bacterial chromosome and demonstrate therapeutic efficacy in vitro and in vivo.ResultsThe attenuated tumour targeting Salmonella typhimurium SL7207 strain was modified to carry chromosomally integrated shRNA expression cassettes at the xylA locus. The colorectal cancer cell lines SW480, HCT116 and breast cancer cell line MCF7 were used to demonstrate the ability of these modified strains to perform intracellular infection and deliver effective RNA and protein knockdown of the target gene c-Myc. In vivo therapeutic efficacy was demonstrated using the Lgr5creERT2Apcflx/flx and BlgCreBrca2flx/flp53flx/flx orthotopic immunocompetent mouse models of colorectal and breast cancer, respectively. In vitro co-cultures of breast and colorectal cancer cell lines with modified SL7207 demonstrated a significant 50–95% (P < 0.01) reduction in RNA and protein expression with SL7207/c-Myc targeted strains. In vivo, following establishment of tumour tissue, a single intra-peritoneal administration of 1 × 106 CFU of SL7207/c-Myc was sufficient to permit tumour colonisation and significantly extend survival with no overt toxicity in control animals.ConclusionsIn summary we have demonstrated that tumour tropic bacteria can be modified to safely deliver therapeutic levels of gene knockdown. This technology has the potential to specifically target primary and secondary solid tumours with personalised therapeutic payloads, providing new multi-cancer detection and treatment options with minimal off-target effects. Further understanding of the tropism mechanisms and impact on host immunity and microbiome is required to progress to clinical translation

A spatial model of autocatalytic reactions

Biological cells with all of their surface structure and complex interior stripped away are essentially vesicles - membranes composed of lipid bilayers which form closed sacs. Vesicles are thought to be relevant as models of primitive protocells, and they could have provided the ideal environment for pre-biotic reactions to occur. In this paper, we investigate the stochastic dynamics of a set of autocatalytic reactions, within a spatially bounded domain, so as to mimic a primordial cell. The discreteness of the constituents of the autocatalytic reactions gives rise to large sustained oscillations, even when the number of constituents is quite large. These oscillations are spatio-temporal in nature, unlike those found in previous studies, which consisted only of temporal oscillations. We speculate that these oscillations may have a role in seeding membrane instabilities which lead to vesicle division. In this way synchronization could be achieved between protocell growth and the reproduction rate of the constituents (the protogenetic material) in simple protocells.Comment: Submitted to Phys. Rev.