Targeting head and neck squamous cell carcinoma through NQO1-mediated cytotoxicity

Head and neck squamous cell carcinomas (HNSCC) are a group of anatomically diverse cancers characterized by their resistance to traditional chemotherapy and radiotherapy modalities. Given that as diagnostic and therapeutic strategies in cancer treatment have seen great improvements over the last several decades, it would be only logical that the prognosis of HNSCC should improve. However, this has not been the case as the prognosis for HNSCC has remained unchanged over the last several decades, highlighting a need for new treatment strategies. One potential strategy that has demonstrated potential in a variety of other solid tumors is NQO1-targeted therapy. In this strategy the overexpression of NQO1 can be taken advantage of by the DNQ derivative IB-DNQ which is a futile substrate for NQO1 that generates high levels of cytotoxic ROS selectively inside the cancer cell. Given the high prevalence of NQO1 in HNSCC tumors this appears to be a promising strategy for treating this disease. Described in Chapter 2 is the evaluation of IB-DNQ in HNSCC cell lines as well as in feline oral squamous cell carcinoma cell lines (FOSCC). The effectiveness of IB-DNQ was found to be directly correlated with the expression of NQO1 in these cell lines. The pharmacokinetic profile and tolerability of IB-DNQ was determined in healthy research cats and parameters from these analyses were used to conduct in vitro experiments to mimic these conditions. These experiments showed that tumors expressing NQO1 should respond to treatment with IB-DNQ. Preliminary treatments of cats with FOSCC with IB-DNQ as a single agent, as well as in combination with ionizing radiation have yielded positive/promising responses in several cats. Described in Chapter 3 is the investigation into enhancing the current therapeutic window of NQO1-targeted therapy. A prodrug approach to IB-DNQ was attempted to increase solubility and/or reduce off-target toxicity. A secondary approach involving the synthesis of novel derivatives of IB-DNQ containing modifications at a site not previously explored in the SAR of the molecule was also conducted. While the few derivatives synthesized to date all have experienced loss in potency, this site is primed for further investigation and derivatization. Finally, an approach revisiting previously synthesized derivatives of DNQ was implemented in attempts to find a derivative with a greater maximum tolerated dose (MTD) or more favorable pharmacokinetics. Future studies involving NQO1-independent ROS generation, methemoglobin formations and tumor penetrations are currently being investigated to differentiate DNQ derivatives and identify a lead compound. Ongoing clinical evaluation of NQO1-targeted therapy in feline OSCC aims to establish IB-DNQ as an effective treatment modality as well as strengthen its case for translation into humans

Mathematical modeling of blanched and unblanched solar dried ginger rhizome varieties.

This research examines the mathematical modelling of blanched and unblanched solar dried ginger rhizome varieties. The Umudike ginger I and II (UG I and UG II) were blanched with an Electric water bath in the Soil and Water Laboratory, Agricultural and Bioresources Engineering Department, Michael Okpara University of Agriculture Umudike, Abia State. The samples UG I and UG II, were blanched for 3, 6, and 9 minutes at 50℃ respectively. Each samples with the treatment were subjected to active solar drying in sequence. Also, blanched and unblanched UG I and UG II were subjected to active solar drying. The treatment was carried out at 10mm thickness for UG I and UG II rhizome. There were ten different mathematical drying models compared based on the correlation coefficient, mean bias error, root mean square error and reduced chi-square method. The various models used are efficient thin layer drying models and its best fitted model varies due to the blanched and unblanched treatments of UG I and UG II. It was also used to validate and predict equations for all the treatments. The Henderson and Pabis model was recommended for predicting the drying characteristics of blanched and unblanched UG I and UG II ginger rhizomes

Factors Associated with Negative Outcomes in Competency Restoration

This study investigated the associations between demographic, clinical, and legal variables with negative outcomes in competency restoration (CR), which included ultimate findings of incompetence to stand trial (IST), extensions to length of stay (LOS), and recommitment to CR pre-adjudication. Correlates between competency prong level findings in evaluation reports were examined for associations with defendant measures of performance in treatment. A sample (n = 250) was composed of archival data of discharged state hospital patients committed for competency restoration. Average LOS for patients in this sample was 137 days. Commitments were extended for 34% of patients at least once (n =86), and 8% (n = 20) were recommitted for CR pre-adjudication. Lower educational attainment and poor participation in competency education were predictive of IST findings and extensions to LOS. Individuals charged with violent crimes were more likely to face extensions to CR commitments. Those who had a history of CR admissions for prior criminal charges, and those who were restrained for dangerous or disruptive behavior during their current admission, were more likely be recommitted to CR prior to adjudication of their index charge(s). An evaluator opinion of a defendant’s inability to comport themselves appropriately in court was significantly linked to poor medication compliance. The implications of these findings are discussed in the context of the existing body of competency related literature, with suggested considerations offered for future studies exploring correlates and predictors of recommitment for competency restoration

A two-way photonic interface for linking Sr+ transition at 422 nm to the telecommunications C-band

We report a single-stage bi-directional interface capable of linking Sr+ trapped ion qubits in a long-distance quantum network. Our interface converts photons between the Sr+ emission wavelength at 422 nm and the telecoms C-band to enable low-loss transmission over optical fiber. We have achieved both up- and down-conversion at the single photon level with efficiencies of 9.4% and 1.1% respectively. Furthermore we demonstrate noise levels that are low enough to allow for genuine quantum operation in the future.Comment: 5 pages, 4 figure

Square Wave Voltammetric Determination of Penicillin V in Sodium Dodecyl Sulfate Containing Media on Glassy Carbon Electrode

The effect of adding sodium dodecyl sulfate (SDS), a surface-active agent to acetate buffer solution containing penicillin V was investigated. The voltammetric responses of penicillin V on glassy carbon electrode was a function of the concentration of penicillin V, surfactant and pH. Addition of SDS to the penicillin V containing acetate buffer solution (ABS) was found to enhance the voltammetric oxidation current signal by about 10 times with insignificant shift of the oxidation potentials. With this electrochemical method, the optimal pH and SDS concentration were found to be pH 4.5 and 0.347M respectively. Using cyclic voltammetry, the oxidation potential for penicillin V were found to be 1.61V vs. Ag/AgCl in SDS/ABS, pH 4.5 and 1.55V vs. Ag/AgCl in ABS, pH 4.5. Linear concentration range were also investigated using square wave voltammetry and found to lie in the range of 0.04 – 34.6µM penicillin V in SDS/ABS, pH 4.5 and 3.5 – 14.0µM penicillin V in ABS, pH 4.5. Limits of detection were also found to be 0.04µM penicillin V in SDS/ABS, pH 4.5 and 3.5µM penicillin V in ABS, pH 4.5 and limits of quantitation were 0.12µM penicillin V in SDS/ABS, pH 4.5 and 14µM penicillin V in ABS, pH 4.5.Foreign substances like Na+, K+, Mg2+, Zn2+, Ca2+, Fe3+, Cu2+, Cl-, NO3-, PO43- and SO42- did not have any significant effect on the voltammetric currents of penicillin V. These results confirm that this electrochemical method is sensitive enough to be used in the determination of penicillin V in diverse environmental and clinical samples

Voltammetric Determination of Penicillin G in Sodium Dodecyl Sulfate/acetate Buffer Media on Glassy Carbon Electrode

The presence of residues of penicillin in food products like milk and meat of animal origin exerts negative impact on public health such as drug resistance diseases and severe allergic responses. This work reports development of a simple voltammetric method for detection of penicillin using sodium dodecyl sulfate (SDS) in acetate buffer solution (ABS) on glassy carbon electrode. Addition of SDS to the penicillin G containing acetate buffer solution (ABS) was found to enhance the voltammetric oxidation current signal by about 5 times with insignificant shift of the oxidation potentials. Using cyclic voltammetry, the oxidation potentials for penicillin G were found to be 1.65V vs. Ag/AgCl in SDS/ABS, pH 4.5 and 1.60V vs. Ag/AgCl in ABS, pH 4.5. The diffusion coefficients for penicillin G were found to be 6.01x10-7 cm2/sec and 1.39x10-6 cm2/sec in ABS, pH 4.5 and SDS/ABS, pH 4.5 respectively. Linear concentration range were also investigated using square wave voltammetry and found to lie in the range of 1.25 – 15µM penicillin G in SDS/ABS, pH 4.5 and 2.5 – 10µM penicillin G in ABS, pH 4.5.Limits of detection were also found to be 1.25µM and 2.5µM penicillin G in SDS/ABS, pH 4.5 and ABS, pH 4.5 respectively while limits of quantitation were 3.75µM penicillin G in SDS/ABS, pH 4.5 and 7.5µM penicillin G in ABS, pH 4.5. Possible interferants like Na+, K+, Zn2+, Ca2+, Fe3+, Cl-, NO3-, PO43- and SO42- did not have any significant effect on the anodic currents and oxidation potentials of the penicillin G. These results show that the developed method is sensitive enough for use in the analysis of penicillin G in diverse real samples

TrES-2: The First Transiting Planet in the Kepler Field

We announce the discovery of the second transiting hot Jupiter discovered by the Trans-atlantic Exoplanet Survey. The planet, which we dub TrES-2, orbits the nearby star GSC 03549-02811 every 2.47063 days. From high-resolution spectra, we determine that the star has T_eff = 5960 +/- 100 K and log(g) = 4.4 +/- 0.2, implying a spectral type of G0V and a mass of 1.08 +0.11/-0.05 M_sun. High-precision radial-velocity measurements confirm a sinusoidal variation with the period and phase predicted by the photometry, and rule out the presence of line-bisector variations that would indicate that the spectroscopic orbit is spurious. We estimate a planetary mass of 1.28 +0.09/-0.04 M_Jup. We model B, r, R, and I photometric timeseries of the 1.4%-deep transits and find a planetary radius of 1.24 +0.09/-0.06 R_Jup. This planet lies within the field of view of the NASA Kepler mission, ensuring that hundreds of upcoming transits will be monitored with exquisite precision and permitting a host of unprecedented investigations.Comment: Accepted for publication in ApJL. 15 pages, 2 figure

Field and laboratory validation of remote rover operations Science Team findings: The CanMars Mars Sample Return analogue mission

The CanMars Mars Sample Return Analogue Deployment (MSRAD) was a closely simulated, end-to-end Mars Sample Return (MSR) mission scenario, with instrumentation, goals, and constraints modeled on the upcoming NASA Mars 2020 rover mission; this paper reports on the post-mission validation of the exercise. The exercise utilized the CSA Mars Exploration Science Rover (MESR) rover, deployed to Utah, USA, at a Mars-analogue field site. The principal features of the field site located near Green River, Utah are Late Jurassic inverted, fluvial paleochannels, analogous to features on Mars in sites being considered for the ESA ExoMars rover mission and present within the chosen landing site for the Mars 2020 rover mission. The in-simulation (“in-sim”) mission operations team worked remotely from The University of Western Ontario, Canada. A suite of MESR-integrated and hand-held spectrometers was selected to mimic those of the Mars 2020 payload, and a Utah-based, on-site team was tasked with field operations to carry out the data collection and sampling as commanded by the in-sim team. As a validation of the in-sim mission science findings, the field team performed an independent geological assessment. This paper documents the field team's on-site geological assessment and subsequent laboratory and analytical results, then offers a comparison of mission (in-sim) and post-mission (laboratory) science results. The laboratory-based findings were largely consistent with the in-sim rover-derived data and geological interpretations, though some notable exceptions highlight the inherent difficulties in remote science. In some cases, available data was insufficient for lithologic identification given the absence of other important contextual information (e.g., textural information). This study suggests that the in-sim instruments were largely adequate for the Science Team to characterize samples; however, rover-based field work is necessarily hampered by mobility and time constraints with an obvious effect on efficiency but also precision, and to some extent, accuracy of the findings. The data show a dearth of preserved total organic carbon (TOC) – used as a proxy for ancient biosignature preservation potential – in the fluvial-lacustrine system of this field site, suggesting serious consideration with respect to the capabilities and opportunities for addressing the Mars exploration goals. We therefore suggest a thorough characterization of terrestrial sites analogous to those of Mars rover landing sites, and in-depth field studies like CanMars as important, pre-mission strategic exercises