Guided-Inquiry in Biochemistry Laboratory Course Improves Lab Math Skills

Biochemistry graduates pursuing research-related careers must master basic quantitative skills. Laboratory courses present students opportunities to practice lab math skills such as dilution and solution calculations. Employers and researchers have reported inadequate math skills among bioscience graduates and there is a need to evaluate the effectiveness of laboratory teaching approaches in increasing students’ lab math skills. In this threeyear study, we examined the impact of guided-inquiry learning on students’ ability to perform laboratory calculations required for experimental design. An upper-level undergraduate biochemistry laboratory course was divided into sections taught using an inquiry approach where students design their own experiments or a cookbook approach where protocols are provided. We wrote a Lab Math Test to measure students’ lab math skills and administered this test as pre- and post-assessment to students in all sections. Students’ lab math skills significantly improved from pre- to posttest scores for inquiry sections (1.18 ± 0.25 (SE) to 4.22 ± 0.37 (SE)) compared to cookbook sections (1.10 ± 0.18 (SE) to 2.89 ± 0.25 (SE)), suggesting that the inquiry approach was more effective in increasing students’ lab math skills. Data showed significantly higher long-term gains for students in inquiry sections during a project-based research experience in the subsequent course. Inquiry learning can lead to a more engaging laboratory course experience and also have the positive side effect of increasing students’ basic lab math skill

Mechanical structures and thermal management scheme for HiCIBaS's stratospheric balloon mission

Le projet HiCIBaS (High-Contrast Imaging Balloon System) est une mission de télescope à ballon dirigé dans le but de l'imagerie exoplanète en utilisant des techniques à contraste élevé. Pour la première mission en 2018, les principaux objectifs étaient de développer les systèmes nécessaires et de valider leurs performances, d'acquérir des données de vol et de prouver la capacité de survie de tous les systèmes et composants majeurs dans des conditions proches de l'espace. Ce projet de maîtrise porte sur deux aspects de la charge utile : la conception de la monture de télescope alt-az dynamique pour le système de pointage et le développement des sangles thermiques personnalisées pour le système optique. La monture du télescope est la structure qui supporte le télescope et permet aux moteurs du système de pointage de le diriger vers la position souhaitée. Les sangles thermiques personnalisées sont une solution développée pour dissiper la chaleur générée par les principaux composants du système optique (caméras, contrôleurs, etc.). Les deux solutions ont été testées lors d’un vol de nuit en août 2018 dans le cadre de la campagne STRATOS de l’agence spatiale canadienne à Timmins, en Ontario. Ce mémoire définira les exigences des deux systèmes, présentera le développement des conceptions, détaillera les analyses et les tests effectués, démontrera la conformité aux exigences, commentera sur les performances de la mission et donner des conseilsdes moyens d'améliorer les deux conceptions pour les futures itérations du projet.The HiCIBaS (High-Contrast Imaging Balloon System) project is a balloon-borne telescope mission with the big-picture goal of exoplanet-imaging using high-contrast techniques. For the scope of the pilot mission in 2018, the main goals were to develop the necessary systems and validate their performance, acquire flight data, and prove the survivability of all systems and major components in near-space conditions. This Master’s project deals with two aspects of the overall payload : the design of the dynamic alt-az telescope mount for the pointing system and the development of the custom thermal straps for the optics system. The telescope mount is the structure that supports the telescope and allows the pointing system’s motors to direct it to the desired position. The custom thermal straps are a solution that was developed to dissipate the heat generated by the optics system’s main components (cameras, controllers, etc.). Both solutions were tested during an overnight flight in August of 2018 under the Canadian Space Agency’s STRATOS campaign in Timmins, Ontario. This mémoire will define the requirements for both systems, present the development of the designs, detail the analyses and tests performed, demonstrate conformance to the requirements, commenton mission performances, and provide insight on ways to improve both designs for future iterations

Therapeutic Exploitation of Metabolic Checkpoints In Cancer Cells

During the G1 phase of the cell cycle, normal cells respond to growth factors and nutrients prior to entering S-phase to replicate its genome. We previously reported that the growth factor-mediated restriction point is distinguishable from a series of late G1 metabolic checkpoints mediated by essential amino acids (EAAs), the conditionally essential amino acid glutamine (Gln), and mTOR – the mammalian target of rapamycin. Mutations in genes encoding proteins that regulate G1 cell cycle progression are observed in virtually all cancers. We observed that cancer cells with K-Ras mutations bypass the late G1 Gln checkpoint when deprived of Gln and instead arrest in S-phase. Significantly, this created a synthetic lethality for rapamycin. Whereas rapamycin arrests cells in late G1, in S-phase rapamycin induces apoptosis. While depriving cells of Gln can be achieved in culture, this is not a viable option in an animal. However, K-Ras-driven cancer cells utilize Gln via a novel transaminase reaction whereby Gln is first deaminated to glutamate and then glutamate is deamidated to a-ketoglutarate, with the concomitant conversion of oxaloacetate to aspartate. This transamination reaction can be inhibited by aminooxyacetate, which mimics Gln deprivation and causes S-phase arrest – creating synthetic lethality for rapamycin. Since S-phase arrest created a synthetic lethality for rapamycin, we investigated the molecular basis for the S-phase arrest. We found that S-phase arrest was due to an inability to generate deoxynucleotides needed for DNA synthesis in the absence of glutamine. The lack of Gln suppressed deoxynucleotides biosynthesis, which in turn induced replicative stress. The replicative stress activated the ataxia telangiectasia and Rad3-related protein (ATR)-mediated DNA damage pathway, which caused S-phase arrest. Of significance, aspartate, which is a critical metabolite for deoxynucleotides biosynthesis and is generated by the transaminase reaction between glutamate and oxaloacetate, rescued the S-phase arrest caused by inhibition of glutamine utilization. The presence of distinct metabolic checkpoints in late G1 for EAAs and Gln led us to look for additional checkpoints that monitor the presence of critical nutrients. Since lipids are critical for membrane biosynthesis, we investigated whether serum lipids were important for G1 cell cycle progression. We found that when put in delipidated serum, cells arrest in late G1 at a distinct site downstream from the Gln checkpoint and upstream from the mTOR site. Intriguingly, this checkpoint is dysregulated in clear cell renal carcinoma cells. These cells continue to replicate in the absence of lipids until they ultimately starve themselves to death. In summary, we have identified a series of late G1 metabolic checkpoints that are dysregulated in specific cancer cell lines. It is speculated that when these checkpoints are dysregulated in cancer cells, there are novel opportunities for therapeutic intervention

Risk of Mortality (including Sudden Cardiac Death) and Major Cardiovascular Events in Users of Olanzapine and Other Antipsychotics: A Study with the General Practice Research Database.

Objective. Assess risk of cardiac events and mortality among users of olanzapine and other antipsychotics relative to nonusers. Methods. The General Practice Research Database was used to identify cohorts of antipsychotic users and nonusers with psychiatric illness. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Results. 183,392 antipsychotic users (including 20,954 olanzapine users) and 193,920 psychiatric nonusers were identified. There was a significantly higher rate of cardiac mortality (adjusted RR [aRR]: 1.53, CI, 1.12-2.09) in olanzapine users relative to psychiatric nonusers, consistent with findings for both atypical and typical antipsychotics. Relative to psychiatric nonusers, no increased risk of all-cause mortality was observed among olanzapine users (aRR: 1.04, CI, 0.93-1.17), but elevated all-cause mortality risk was observed when compared to all antipsychotic users (aRR: 1.75, CI, 1.64-1.87). There was no increased risk of CHD or VA among olanzapine users relative to psychiatric nonusers, consistent with findings for atypical but not typical antipsychotics. SCD cases were uncommon. Conclusions. Use of antipsychotic agents was associated with increased risk of all-cause and cardiac mortality. Patients treated with olanzapine were found to be at increased risk of cardiac mortality versus psychiatric nonusers

COMPARATIVE STUDY OF BLUETOOTH, 802.11 AND HIPERLAN

ABSTRACT This manuscript presents comparison of various wireless services. Wireless network are used to communicate with different device which may be computer or any other consumer devices like ATM machines, Mobile Internet, LANs, etc. The wireless communication is used at commercial as well as personal use also to achieve the higher speed of data transfer, easy communication and utilization of the devices. In this area as infrastructural facilities are increased wireless services are widely used and gaining popularity among users this dissertation will help to identify advantages, limitations of wireless services (Like 802.11(IEEE 802.11), HIPERLAN, Home-RF (Home Radio Frequency), and Bluetooth) based on comparison of various parameters

Risk of mortality (including sudden cardiac death) and major cardiovascular events in atypical and typical antipsychotic users: a study with the general practice research database.

Objective. Antipsychotics have been associated with increased cardiac events including mortality. This study assessed cardiac events including mortality among antipsychotic users relative to nonusers. Methods. The General Practice Research Database (GPRD) was used to identify antipsychotic users, matched general population controls, and psychiatric diseased nonusers. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Sensitivity analyses were conducted for age, dose, duration, antipsychotic type, and psychiatric disease. Results. 183,392 antipsychotic users (115,491 typical and 67,901 atypical), 544,726 general population controls, and 193,920 psychiatric nonusers were identified. Nonusers with schizophrenia, dementia, or bipolar disorder had increased risks of all-cause mortality compared to general population controls, while nonusers with major depression had comparable risks. Relative to psychiatric nonusers, the adjusted relative ratios (aRR) of all-cause mortality in antipsychotic users was 1.75 (95% CI: 1.64-1.87); cardiac mortality 1.72 (95% CI: 1.42-2.07); SCD primary definition 5.76 (95% CI: 2.90-11.45); SCD secondary definition 2.15 (95% CI: 1.64-2.81); CHD 1.16 (95% CI: 0.94-1.44); and VA 1.16 (95% CI: 1.02-1.31). aRRs of the various outcomes were lower for atypical versus typical antipsychotics (all-cause mortality 0.83 (95% CI: 0.80-0.85); cardiac mortality 0.89 (95% CI: 0.82-0.97); and SCD secondary definition 0.76 (95% CI: 0.55-1.04). Conclusions. Antipsychotic users had an increased risk of cardiac mortality, all-cause mortality, and SCD compared to a psychiatric nonuser cohort

Amino Acids and mTOR Mediate Distinct Metabolic Checkpoints in Mammalian G1 Cell Cycle

Objective In multicellular organisms, cell division is regulated by growth factors (GFs). In the absence of GFs, cells exit the cell cycle at a site in G1 referred to as the restriction point (R) and enter a state of quiescence known as G0. Additionally, nutrient availability impacts on G1 cell cycle progression. While there is a vast literature on G1 cell cycle progression, confusion remains – especially with regard to the temporal location of R relative to nutrient-mediated checkpoints. In this report, we have investigated the relationship between R and a series of metabolic cell cycle checkpoints that regulate passage into S-phase. Methods We used double-block experiments to order G1 checkpoints that monitor the presence of GFs, essential amino acids (EEAs), the conditionally essential amino acid glutamine, and inhibition of mTOR. Cell cycle progression was monitored by uptake of [3H]-thymidine and flow cytometry, and analysis of cell cycle regulatory proteins was by Western-blot. Results We report here that the GF-mediated R can be temporally distinguished from a series of late G1 metabolic checkpoints mediated by EAAs, glutamine, and mTOR – the mammalian/mechanistic target of rapamycin. R is clearly upstream from an EAA checkpoint, which is upstream from a glutamine checkpoint. mTOR is downstream from both the amino acid checkpoints, close to S-phase. Significantly, in addition to GF autonomy, we find human cancer cells also have dysregulated metabolic checkpoints. Conclusion The data provided here are consistent with a GF-dependent mid-G1 R where cells determine whether it is appropriate to divide, followed by a series of late-G1 metabolic checkpoints mediated by amino acids and mTOR where cells determine whether they have sufficient nutrients to accomplish the task. Since mTOR inhibition arrests cells the latest in G1, it is likely the final arbiter for nutrient sufficiency prior to committing to replicating the genome

Predictors of Treatment Failure in HIV-Positive Children Receiving Combination Antiretroviral Therapy: Cohort Data From Mozambique and Uganda

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