Inflation divergence within the SADC

This study investigates the feasibility of a monetary union in the Southern African Development Community (SADC) by testing for inflation convergence for 11 members. Quarterly data over the period 1992:3 – 2001:4 are employed. Various panel unit root tests are applied to test whether the purchasing power parity (PPP) holds. Overall, strong evidence of a unit root is found. This implies inflation divergence among the SADC members.PPP, Inflation Convergence, Panel Unit Root Tests, SADC.

Aluminum Consumption and Economic Growth: Evidence from Rich Countries

The article attempts to test the aluminum consumption-economic growth nexus for 20 rich economies for the period 1970-2009. Various panel data unit root and cointegration tests are applied. The series are found to be integrated of order one and cointegrated, especially after controlling for cross-sectional dependence. Moreover, the Blundell-Bond system generalized methods-of-moments is employed to conduct a panel causality test in a vector error-correction mechanism setting. Unidirectional causality running from aluminum consumption to real GDP is uncovered in the short-run, while real GDP is found to Granger-cause aluminum consumption in the long-run. Moreover, a 1% increase in real GDP generates an increase of 0.44% in aluminum consumption in the long-run for the whole pane

The Wealth-Health Nexus: New Global Evidence

Using a world sample of countries, this paper re-examines the U-shaped relationship between per capita GDP (wealth) and life expectancy at birth (health). Since cross-sectional dependence across countries is detected, second-generation panel unit root and cointegration tests are employed. All the variables are found to be integrated in one order as well as cointegrated. Various quadratic specifications are also employed and the hypothesis is confirme

Buckling Analysis and Optimum Design of Multidirectionally Stiffened Composite Curved Panel

Continuous filament grid-stiffened structure is a stiffening concept that combines structural efficiency and damage tolerance. However, buckle resistant design optimization of such structures using a finite element method is expensive and time consuming due to the number of design parameters that can be varied. An analytical optimization procedure which is simple, efficient and supports the preliminary design of grid-stiffened structures for application to combined loading cases is needed. An analytical model for a general grid-stiffened curved panel is developed using an improved smeared theory with a first-order, shear-deformation theory to account for transverse shear flexibilities and local skin-stiffener interaction effects. The local skin-stiffener interaction effects are accounted for by computing the stiffness due to the stiffener and the skin in the skin-stiffener region using the neutral surface profile of the skin-stiffener semi-infinite plate model. The neutral surface profile for the skin-stiffener semi-infinite plate model is obtained analytically using a stress function approach, minimum potential energy principle, and statics conditions. Analysis methods for buckling of general parallelogram-shaped and general triangular-shaped curved panels are developed. These analyses are required in order to assess the local buckling of grid-stiffened curved skin segments. The buckling analysis makes use of circulation functions as Ritz functions which account for material anisotropy and different boundary conditions. The local buckling of stiffener segments between stiffener interaction points are also assessed. Using these analyses and a genetic algorithm as optimizer, an optimization tool is developed for minimum weight design of composite grid-stiffened panel subjected to combined in-plane loads with a global buckling design constraint. Design variables are the axial and transverse stiffener spacings, the stiffener height and thickness, and the stiffener pattern. Results are presented for buckling loads of composite grid-stiffened panels which are obtained using the improved smeared theory and are compared with detailed finite element analysis. Buckling loads for anisotropic skewed and triangular plates, and curved panels are presented and compared with results from finite element analysis. Finally, designs for grid-stiffened panels obtained using the design optimization process are presented

The Discovery and Characterization of a Novel Family of Anti- Cancer Compounds

Cancer is amongst the leading causes of death in the world and has plagued humanity for far longer than some would expect. We have come a long way in understanding the physiological changes that correlate with cancer progression, but treatment options remain limited. In this thesis, I developed a high-throughput pipeline to screen thienoisoquinoline derivatives synthesized by Dr. Forgione’s laboratory for their efficacy in reducing cancer cell viability. These derivatives were strategically designed to share a common ¬scaffold and have three functional groups amenable to modifications. From >40 derivatives, we identified our lead compound C75. We characterized the mechanism of action of C75 at a molecular and cellular level to develop a better understanding of its efficacy and selectivity for some cell types over others. Through in vitro assays, we found that C75 prevents microtubule polymerization, destabilizes microtubules, and binds to tubulin at the same site as colchicine (another microtubule-targeting drug). In line with its effects on microtubules, C75 causes mitotic arrest and spindle phenotypes in multiple cancer cell lines in the nanomolar range. However, through comparative studies with colchicine, we found that while colchicine causes a gradual decrease in microtubules and spindle pole collapse in cells, similar concentrations of C75 cause a rapid loss of microtubules and spindle pole fragmentation followed by microtubule re-growth to form multipolar spindles. In addition, C75 and colchicine synergize for reduced viability and spindle phenotypes. Importantly, the phenotypes caused by C75 are similar to those caused by the depletion of ch-TOG, a microtubule polymerase, and tubulin and ch-TOG are displaced and oscillate in C75-treated cells. This suggests that C75 directly causes microtubule depolymerization in cells, or indirectly causes this via inhibiting ch-TOG. We also discovered that C75 has higher efficacy in triple negative breast cancer (TNBC) cells compared to other cell types, suggesting that this could be an ideal group of cancers to explore a potential use for. It will be important to determine if C75 retains its efficacy in TNBCs that are resistant to Taxol, which arises in patients after repeated Taxol use leaving them with few alternative treatment options. We also identified a new derivative that has an even higher efficacy in TNBCs compared to C75, and we are determining if this will be a new lead compound. With a strong understanding of how these compounds work at the molecular and cellular level, we are positioned to carry out in vivo studies to determine their potential for use for treating TNBCs

Optimal Design of General Stiffened Composite Circular Cylinders for Global Buckling with Strength Constraints

A design strategy for optimal design of composite grid-stiffened cylinders subjected to global and local buckling constraints and strength constraints was developed using a discrete optimizer based on a genetic algorithm. An improved smeared stiffener theory was used for the global analysis. Local buckling of skin segments were assessed using a Rayleigh-Ritz method that accounts for material anisotropy. The local buckling of stiffener segments were also assessed. Constraints on the axial membrane strain in the skin and stiffener segments were imposed to include strength criteria in the grid-stiffened cylinder design. Design variables used in this study were the axial and transverse stiffener spacings, stiffener height and thickness, skin laminate stacking sequence and stiffening configuration, where stiffening configuration is a design variable that indicates the combination of axial, transverse and diagonal stiffener in the grid-stiffened cylinder. The design optimization process was adapted to identify the best suited stiffening configurations and stiffener spacings for grid-stiffened composite cylinder with the length and radius of the cylinder, the design in-plane loads and material properties as inputs. The effect of having axial membrane strain constraints in the skin and stiffener segments in the optimization process is also studied for selected stiffening configurations

Shortening the Half-Life of the CRISPR/dCas9 System

Shortening the half-life of genetic engineering tools such as dCas9-VP64 can become a pivotal component to regulate many cellular networks, allowing periodic gene expression and protein levels, thereby governing vital cellular processes. However, currently this effector protein has a prolonged half-life in cells and can cause adverse effects by binding to other regions or interacting with other transcriptional or translational machinery. This thesis aims to explore the N-End Rule as a novel approach to achieve shorter half-life dCas9-VP64, offering tighter control for future applications in synthetic circuits. The need for shorter half-life gene effectors arises from the cytotoxic effects observed with persistence exposure that can lead to off-target effects and unintended modifications, hampering their accuracy and reliability in genetic manipulation. The introduction of short-lived effector proteins also holds significant promise for enhancing temporal control and predictable timing of protein degradation. The central hypothesis driving this research is that the N-End Rule can be harnessed to shorten the half-life of the artificial transcriptional activator dCas9-VP64 (Varshavsky, 1998). Through site-directed mutagenesis, four amino acids were introduced at the N-terminus of dCas9-VP64, including alanine, valine, serine, and cysteine. These amino acid residues were identified as destabilizing when positioned at N-termini based on the N-acetylation N-End Rule (Nguyen, K.T. et al., 2018). Experimental design involved genetic construct development, fusion with a fluorescent protein tag for visualization, and validation of N-terminus mutations. Using cycloheximide, a protein synthesis and translation inhibitor, the steady-state level of the dCas9-VP64-eGFP protein was monitored through eGFP fluorescence from a microplate reader assay and through western blot analysis. We observed different phenotypes during induction and tracking of fusion proteins' signals. Protein half-life was measured using the first order rate kinetic equation for protein degradation. The results revealed the differential half-life of dCas9-VP64 variants, showcasing the potential of the N-End Rule in achieving shorter half-life. The cysteine variant demonstrated the shortest half-life of 37 minutes, indicating its potential suitability for synthetic circuits. dCas9-VP64-eGFP with the wild-type N-terminus exhibited a half-life of 57 minutes, while serine and alanine variants displayed approximately 54 and 61 minutes, respectively. In conclusion, this thesis contributes to the advancement of strategies for shortening the half-life of proteins. The implementation of the N-End Rule to achieve this goal exemplifies its potential in optimizing genetic behavior control in future applications with synthetic circuits. By harnessing the N-End Rule, researchers can pave the way for future innovations and advancements in the realm of genetic engineering and molecular biology

Optimal Design of Grid-Stiffened Composite Panels Using Global and Local Buckling Analysis

A design strategy for optimal design of composite grid-stiffened panels subjected to global and local buckling constraints is developed using a discrete optimizer. An improved smeared stiffener theory is used for the global buckling analysis. Local buckling of skin segments is assessed using a Rayleigh-Ritz method that accounts for material anisotropy and transverse shear flexibility. The local buckling of stiffener segments is also assessed. Design variables are the axial and transverse stiffener spacing, stiffener height and thickness, skin laminate, and stiffening configuration. The design optimization process is adapted to identify the lightest-weight stiffening configuration and pattern for grid stiffened composite panels given the overall panel dimensions, design in-plane loads, material properties, and boundary conditions of the grid-stiffened panel

RAPID analysis of variable stiffness beams and plates: Legendre polynomial triple-product formulation

Copyright © 2017 John Wiley & Sons, Ltd. Numerical integration techniques are commonly employed to formulate the system matrices encountered in the analysis of variable stiffness beams and plates using a Ritz based approach. Computing these integrals accurately is often computationally costly. Herein, a novel alternative is presented, the Recursive Analytical Polynomial Integral Definition (RAPID) formulation. The RAPID formulation offers a significant improvement in the speed of analysis, achieved by reducing the number of numerical integrations that are performed by an order of magnitude. A common Legendre Polynomial basis is employed for both trial functions and stiffness/load variations leading to a common form for the integrals encountered. The Legendre Polynomial basis possesses algebraic recursion relations that allow these integrals to be reformulated as triple-products with known analytical solutions, defined compactly using the Wigner (3j) coefficient. The satisfaction of boundary conditions, calculation of derivatives and transformation to other bases is achieved through combinations of matrix multiplication, with each matrix representing a unique boundary condition or physical effect, therefore permitting application of the RAPID approach to a variety of problems. Indicative performance studies demonstrate the advantage of the RAPID formulation when compared to direct analysis using Matlab's ‘integral’ and ‘integral2’. Copyright © 2017 John Wiley & Sons, Ltd