Bioavailability of Citrus Flavanones and Their Effect on Cardiovascular Health Biomarkers

Consumption of flavanones has been associated with a reduction in risk of developing CVD, however flavanone bioavailability varies greatly in the population. The thesis aim was to investigate variations in absorption, as assessed by urinary excretion and, for the first time, the effect of commercially-available citrus supplements on CVD risk biomarkers. In study 1, 15 participants consumed orange juice (OJ; 500 ml: 8 mg naringenin, 42 mg hesperidin/100 ml) and/or soya-nuts (25g): 30 mg daidzein, 57 mg genistein/100 g). Urine was collected at 0, 0-4, 4-8, 8-12, 12-24 and 24-36 hr on each of three separate occasions; saliva was collected hourly (0-8 and 24 hr) after co-ingestion of OJ and soya-nuts. Daidzein was excreted to a greater extent than genistein (27-28% of dose ingested compared to 16-19%), whilst naringenin was excreted to a greater extent than hesperetin (9% vs 2.5-3%). There was a strong positive correlation between excretion of daidzein and genistein (r=0.72, p<0.01), and for hesperetin and naringenin (r=0.72, p< 0.01). Moreover, the amount of naringenin, and daidzein or genistein were correlated when co-ingested (r=0.73, p<0.01; r=0.49, p=0.05). No flavonoid was detected in saliva at any time point. In study 2, 23 overweight participants ingested citrus supplements (114 mg hesperidin) or a placebo daily for 28 days in a randomised, cross-over intervention. Urinary excretion (24 hr) was analysed by LC-MS to determine flavanone metabolite concentration at day-1 or day-28. Hesperetin-3ʹ-O-glucuronide, hesperetin-3ʹ-O-sulfate and hesperetin-7-O-glucuronide were quantified. Supplement flavanones had similar bioavailability to OJ, and there was no cumulative increase in excretion over 28 days. There was a non-significant decrease in blood pressure and fasting blood glucose after supplementation compared to placebo, however pulse amplitude tonometry was not affected. Augmentation index was reduced after supplementation compared to baseline. Although results from this thesis showed no significant change in CVD risk biomarkers, more work should verify the protective mechanism of hesperetin metabolites at different doses on vascular health

Operational performance of a PV generator feeding DC shunt and induction motors with MPPT

This paper presented the transient and operational behavior of a parallel Combination of DC Shunt Motor and IM fed by a photovoltaic generator at different solar irradiance levels. The maximum power point of current/voltage (I/V) characteristic of the PV generator was achieved for different solar intensities, by utilizing an open circuit voltage method. The nonlinear operational behavior of (I/V) characteristics of the PV generator at various solar intensities and the magnetization curve of the ferromagnetic material of the DC shunt motor were both modeled by high order polynomial mathematical expressions. The study investigated the response of the system at different solar irradiance levels and changing the torque loads for both motors and then following step change in solar intensity levels with fixed loading torques for both motors. All numerical simulations were executed using MATLAB software

New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation

Phosphoinositide 3-kinase α (PI3Kα) is a propitious target for designing anticancer drugs. A series of new N\u27-(diphenylmethylene)benzenesulfonohydrazide was synthesized and characterized using FT-IR, NMR (1H and 13C), HRMS, and elemental analysis. Target compounds exhibited an antiproliferative effect against the human colon carcinoma (HCT-116) cell line. Our cheminformatics analysis indicated that the para-tailored derivatives [p-NO2 (3) and p-CF3 (7)] have better ionization potentials based on calculated Moran autocorrelations and ionization potentials. Subsequent in vitro cell proliferation assays validated our cheminformatics results by providing experimental evidence that both derivatives 3 and 7 exhibited improved antiproliferative activities against HCT-116. Hence, our results emphasized the importance of electron-withdrawing groups and hydrogen bond-acceptors in the rational design of small-molecule chemical ligands targeting PI3Kα. These results agreed with the induced-fit docking against PI3Kα, highlighting the role of p-substituted aromatic rings in guiding the ligand-PI3Kα complex formation, by targeting a hydrophobic pocket in the ligand-binding site and forming π-stacking interactions with a nearby tryptophan residue

Hardware acceleration of DNA pattern matching using analog resistive CAMs

DNA pattern matching is essential for many widely used bioinformatics applications. Disease diagnosis is one of these applications since analyzing changes in DNA sequences can increase our understanding of possible genetic diseases. The remarkable growth in the size of DNA datasets has resulted in challenges in discovering DNA patterns efficiently in terms of run time and power consumption. In this paper, we propose an efficient pipelined hardware accelerator that determines the chance of the occurrence of repeat-expansion diseases using DNA pattern matching. The proposed design parallelizes the DNA pattern matching task using associative memory realized with analog content-addressable memory and implements an algorithm that returns the maximum number of consecutive occurrences of a specific pattern within a DNA sequence. We fully implement all the required hardware circuits with PTM 45-nm technology, and we evaluate the proposed architecture on a practical human DNA dataset. The results show that our design is energy-efficient and accelerates the DNA pattern matching task by more than 100× compared to the approaches described in the literature

Experimental study and numerical modeling of the thermo-hydro-mechanical processes in soil freezing with different frost penetration directions

This research work presents an experimental and numerical study of the coupled thermo-hydro-mechanical (THM) processes that occur during soil freezing. With focusing on the artificial ground freezing (AGF) technology, a new testing device is built, which considers a variety of AGF-related boundary conditions and different freezing directions. In the conducted experiments, a distinction is made between two thermal states: (1) The thermal transient state, which is associated with ice penetration, small deformations, and insignificant water suction. (2) The thermal (quasi-) steady state, which has a much longer duration and is associated with significant ice lens formation due to water suction. In the numerical modeling, a special focus is laid on the processes that occur during the thermal transient state. Besides, a demonstration of the micro-cryo-suction mechanism and its realization in the continuum model through a phenomenological retention-curve-like formulation is presented. This allows modeling the ice lens formation and the stiffness degradation observed in the experiments. Assuming a fully saturated soil as a biphasic porous material, a phase-change THM approach is applied in the numerical modeling. The governing equations are based on the continuum mechanical theory of porous media (TPM) extended by the phase-field modeling (PFM) approach. The model proceeds from a small-strain assumption, whereas the pore fluid can be found in liquid water or solid ice state with a unified kinematics treatment of both states. Comparisons with the experimental data demonstrate the ability and usefulness of the considered model in describing the freezing of saturated soils.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659RWTH Aachen (3131

Nucleophilic substitution approach towards 1,3-dimethylbarbituric acid derivatives: new synthetic routes and crystal structures

We describe simple, convenient and high-yielding nucleophilic substitution reactions to synthesize new derivatives of 1,3-dimethylbarbituric acid (1a). Based on its active C5 position, condensing 1a with sulfuryl chloride gives the corresponding 5,5-dichloro-1,3-dimethylbarbituric acid (13). The latter was reacted with silver nitrite and potassium cyanide to afford 5-chloro-5-nitro-1,3-dimethylbarbituric acid (14) and 5-cyano-1,3-dimethylbarbiturate (17), respectively. Furthermore, by employing the nucleophilic character of 2,3-dihydro-1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene (8) the obtained compounds 13 and 14 have been converted to 2-chloro-1,3-diisopropyl-4,5-dimethyl-1H-imidazol-3-ium-1,3-dimethyl-5-nitro-1,3-dimethylbarbiturate (18) and 1,3-dimethylbarbituric acid trimer (21), respectively. X-ray structures for compounds 13, 14, 17, 18 and 21 were determined