The Egyptian Cardiothoracic Surgeon (ECTS - E-Journal)
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Using Whole-Exome Sequencing to Identify Genetic Markers for Carboplatin and Gemcitabine-Induced Toxicities.
No full textPURPOSE: Chemotherapies are associated with significant interindividual variability in therapeutic effect and adverse drug reactions. In lung cancer, the use of gemcitabine and carboplatin induces grade 3 or 4 myelosuppression in about a quarter of the patients, while an equal fraction of patients is basically unaffected in terms of myelosuppressive side effects. We therefore set out to identify genetic markers for gemcitabine/carboplatin-induced myelosuppression. EXPERIMENTAL DESIGN: We exome sequenced 32 patients that suffered extremely high neutropenia and thrombocytopenia (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0 or 1). The genetic differences/polymorphism between the groups were compared using six different bioinformatics strategies: (i) whole-exome nonsynonymous single-nucleotide variants association analysis, (ii) deviation from Hardy-Weinberg equilibrium, (iii) analysis of genes selected by a priori biologic knowledge, (iv) analysis of genes selected from gene expression meta-analysis of toxicity datasets, (v) Ingenuity Pathway Analysis, and (vi) FunCoup network enrichment analysis. RESULTS: A total of 53 genetic variants that differed among these groups were validated in an additional 291 patients and were correlated to the patients' myelosuppression. In the validation, we identified rs1453542 in OR4D6 (P = 0.0008; OR, 5.2; 95% CI, 1.8-18) as a marker for gemcitabine/carboplatin-induced neutropenia and rs5925720 in DDX53 (P = 0.0015; OR, 0.36; 95% CI, 0.17-0.71) as a marker for thrombocytopenia. Patients homozygous for the minor allele of rs1453542 had a higher risk of neutropenia, and for rs5925720 the minor allele was associated with a lower risk for thrombocytopenia. CONCLUSIONS: We have identified two new genetic markers with the potential to predict myelosuppression induced by gemcitabine/carboplatin chemotherapy. Clin Cancer Res; 1-8. ©2015 AACR
Proton Transfer, Hydrogen Bonding, and Disorder in Molecular Complexes: Nitrogen NEXAFS and XPS of Bipyridine-Acid Salts and Co-crystals
No full textSmart Grid security::Protecting user's privacy in Smart Grid applications
No full textSmart Grid (SG) is an electrical grid enhanced with information and communication technology capabilities, so it can support two-way electricity and communication flows among various entities in the grid. The aim of SG is to make the electricity industry operate more efficiently and to provide electricity in a more secure, reliable and sustainable manner. Automated Meter Reading (AMR) and Smart Electric Vehicle (SEV) charging are two SG applications tipped to play a major role in achieving this aim. The AMR application allows different SG entities to collect users' fine-grained metering data measured by users' Smart Meters (SMs). The SEV charging application allows EVs' charging parameters to be changed depending on the grid's state in return for incentives for the EV owners.However, both applications impose risks on users' privacy. Entities having access to users' fine-grained metering data may use such data to infer individual users' personal habits. In addition, users' private information such as users'/EVs' identities and charging locations could be exposed when EVs are charged. Entities may use such information to learn users' whereabouts, thus breach their privacy.This thesis proposes secure and user privacy-preserving protocols to support AMR and SEV charging in an efficient, scalable and cost-effective manner.First, it investigates both applications. For AMR, (1) it specifies an extensive set of functional requirements taking into account the way liberalised electricity markets work and the interests of all SG entities, (2) it performs a comprehensive threat analysis, based on which, (3) it specifies security and privacy requirements, and (4) it proposes to divide users' data into two types: operational data (used for grid management) and accountable data (used for billing). For SEV charging, (1) it specifies two modes of charging: price-driven mode and price-control-driven mode, and (2) it analyses two use-cases: price-driven roaming SEV charging at home location and price-control-driven roaming SEV charging at home location, by performing threat analysis and specifying sets of functional, security and privacy requirements for each of the two cases.Second, it proposes a novel Decentralized, Efficient, Privacy-preserving and Selective Aggregation (DEP2SA) protocol to allow SG entities to collect users' fine-grained operational metering data while preserving users' privacy. DEP2SA uses the homomorphic Paillier cryptosystem to ensure the confidentiality of the metering data during their transit and data aggregation process. To preserve users' privacy with minimum performance penalty, users' metering data are classified and aggregated accordingly by their respective local gateways based on the users' locations and their contracted suppliers. In this way, authorised SG entities can only receive the aggregated data of users they have contracts with. DEP2SA has been analysed in terms of security, computational and communication overheads, and the results show that it is more secure, efficient and scalable as compared with related work.Third, it proposes a novel suite of five protocols to allow (1) suppliers to collect users accountable metering data, and (2) users (i) to access, manage and control their own metering data and (ii) to switch between electricity tariffs and suppliers, in an efficient and scalable manner. The main ideas are: (i) each SM to have a register, named accounting register, dedicated only for storing the user's accountable data, (ii) this register is updated by design at a low frequency, (iii) the user's supplier has unlimited access to this register, and (iv) the user cancustomise how often this register is updated with new data. The suite has been analysed in terms of security, computational and communication overheads.Fourth, it proposes a novel protocol, known as Roaming Electric Vehicle Charging and Billing, an Anonymous Multi-User (REVCBAMU) protocol, to support the priced-driven roaming SEV charging at home location. During a charging session, a roaming EV user uses a pseudonym of the EV (known only to the user's contracted supplier) which is anonymously signed by the user's private key. This protocol protects the user's identity privacy from other suppliers as well as the user's privacy of location from its own supplier. Further, it allows the user's contracted supplier to authenticate the EV and the user. Using two-factor authentication approach a multi-user EV charging is supported and different legitimate EV users (e.g., family members) can be held accountable for their charging sessions. With each charging session, the EV uses a different pseudonym which prevents adversaries from linking the different charging sessions of the same EV. On an application level, REVCBAMU supports fair user billing, i.e., each user pays only for his/her own energy consumption, and an open EV marketplace in which EV users can safely choose among different remote host suppliers. The protocol has been analysed in terms of security and computational overheads.Detail
Comparative study between the R-ODS and DND methods for damage detection in structures
No full textMeasured vibration responses can be processed either in their original time domain or after converting to the frequency domain for the purpose of damage detection. Recently, two new vibration-based methods have been presented separately which successfully identified the location of damage in beam-like structures. One of the methods utilises the vibration responses of cracked structures in time domain and is called deviation from normal distribution (DND). The DND method calculates the difference between actual and normal distribution of vibration responses in time domain to locate cracks. The other method is called residual operational deflection shape (R-ODS) which uses the amplitude and phase of the exciting frequency and its higher harmonics in the frequency domain as a method of crack detection. Previously, these methods were applied only to single cracked beams with sinusoidal excitation and their results were encouraging. Here, the application of the two methods has been extended to multiple cracked beams as well as rotors. Also, the effect of different types of excitations on the detection process using the two methods has been investigated through numerical and experimental examples
The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies.
No full textRapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention
Predictions of covariant chiral perturbation theory for nucleon polarisabilities and polarised Compton scattering
No full textWe update the predictions of the SU(2) baryon chiral perturbation theory for the dipole polarisabilities of the proton, {αE1,βM1}p={11.2(0.7),3.9(0.7)}×10−4fm3, and obtain the corresponding predictions for the quadrupole, dispersive, and spin polarisabilities: {αE2,βM2}p={17.3(3.9),−15.5(3.5)}×10−4fm5, {αE1ν,βM1ν}p={−1.3(1.0),7.1(2.5)}×10−4fm5, and {γE1E1,γM1M1,γE1M2,γM1E2}p={−3.3(0.8),2.9(1.5),0.2(0.2),1.1(0.3)}×10−4fm4. The results for the scalar polarisabilities are in significant disagreement with semi-empirical analyses based on dispersion relations, however the results for the spin polarisabilities agree remarkably well. Results for proton Compton-scattering multipoles and polarised observables up to the Delta(1232) resonance region are presented too. The asymmetries Σ3 and Σ2x reproduce the experimental data from LEGS and MAMI. Results for Σ2z agree with a recent sum rule evaluation in the forward kinematics. The asymmetry Σ1z near the pion production threshold shows a large sensitivity to chiral dynamics, but no data is available for this observable. We also provide the predictions for the polarisabilities of the neutron: {αE1,βM1}n={13.7(3.1),4.6(2.7)}×10−4fm3, {αE2,βM2}n={16.2(3.7),−15.8(3.6)}×10−4fm5, {αE1ν,βM1ν}n={0.1(1.0),7.2(2.5)}×10−4fm5, and {γE1E1,γM1M1,γE1M2,γM1E2}n={−4.7(1.1),2.9(1.5),0.2(0.2),1.6(0.4)}×10−4fm4. The neutron dynamical polarisabilities and multipoles are examined too. We also discuss subtleties related to matching dynamical and static polarisabilities
Coordination polymers from a highly flexible alkyldiamine-derived ligand: structure, magnetism and gas adsorption studies
No full textThe synthesis and structural, magnetic and gas adsorption properties of a series of coordination polymer materials prepared from a new, highly flexible and internally functional tetrakis-carboxybenzyl ligand H4L derived from 1,2-diaminoethane have been examined. The compound poly-[Ni3(HL)2(OH2)4]??2DMF??2H2O 1, a two-dimensional coordination polymer, contains aqua- and carboxylato-bridged trinuclear NiII clusters, the magnetic behaviour of which can be well described through experimental fitting and ab initio modelling to a ferromagnetically coupled trimer with a positive axial zero-field splitting parameter D. Compound poly-[Zn2L]??2DMF??3H2O 2, a three-dimensional coordination polymer displaying frl topology, contains large and well-defined solvent channels, which are shown to collapse on solvent exchange or drying. Compound poly-[Zn2(L)(DMSO)4]??3DMSO??3H2O 3, a highly solvated two-dimensional coordination polymer, displayed poor stability characteristics, however a structurally related material poly-[Zn2(L)(bpe)(DMSO)2]??DMSO??3H2O 4 was prepared under similar synthetic conditions by including the 1,2-bis(4-pyridyl)ethylene bpe co-ligand. Compound 4, containing small one-dimensional solvent channels, shows excellent structural resilience to solvent exchange and evacuation, and the evacuated material displays selective adsorption of CO2 over N2 at 273 K in the pressure range 0???1 atm. Each of the coordination polymers displays subtle differences in the conformation and binding mode of the ligand species, with switching between two distinct conformers (X-shaped and H-shaped), as well as a variable protonation state of the central core, with significant effects on the resulting network structures and physical properties of the materials