Executive Power: Rethinking the Modalities of Control

The Honorable Sundaresh Menon, Chief Justice of the Supreme Court of Singapore, delivered the 2018-2019 Bernstein Lecture in Comparative Law titled Executive Power: Rethinking the Modalities of Control. The Chief Justice discussed the control of executive power in Singapore as compared to other legal systems. Co-sponsored by the Center for International and Comparative Law and the Office of the Dean

On the computation of probabilities and eigenvalues for random and non-random matrices

Thesis (S.M.)--Massachusetts Institute of Technology, Computation for Design and Optimization Program, 2009.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from PDF version of thesis.Includes bibliographical references (p. 43-44).Can you imagine doing hundreds of millions of operations on non-integers and not obtaining a single round-off error? For n < 12, the algorithm used in this thesis does exactly that. We took advantage of a floating point property that we have not seen used before. If only we had quad precision we could have gone even further and extended the algorithm without round-off error for higher values of 'n'. The problem in question concerns whether the eigenvalues are real or complex. The eigenvalues of an n-by-n real random matrix whose elements are independent random variables with standard normal are examined. An exact expression to determine the probability Pn,k that exactly k eigenvalues are real are derived in [1]. This expression was used to compute the probabilities Pn,k, but the computation was achieved only up to n = 9. For higher values of n, the symbolic expressions generated during the course of an algorithm to compute an exact probability as expressed in Mathematica code requires large amounts of memory. In this thesis, we target development of a more efficient algorithm. The symbolic algorithm implemented in Mathematica is converted into an equivalent numerical version and is implemented using MATLAB. After implementing the serial code in MATLAB, the code is parallelized using a client-server parallel computing platform named Star-p. This modified code implementation along with superior hardware in terms of better processor speeds and larger memory, has enabled the probability evaluation for all values of k up to n= 11, and for certain k values for n = 12 and 13.(cont.) An expression for the expected number of real eigenvalues En=o kpn,k is obtained in paper [2]. Results relating the rational and irrational parts of the summations n =o kpn,ki, En k=0 (Pk n,k and En= - n,k 0 k)Pn,k are conjectured. Three eigenvalue algorithms, the block Davidson, the block KrylovSchur and the Locally optimal Block Pre-conditioned Conjugate Gradient Method (LOBPCG) are analyzed and their performance on different types of matrices are studied. The performance of the algorithms as a function of the parameters , block size, number of blocks and the type of preconditioner is also examined in this thesis. The block Krylov Schur Algorithm for the matrices which are used for the experiments have proved to much superior to the others in terms of computation time. Also its been more efficient in finding eigenvalues for matrices representing grids with Neumann boundary conditions which have at least one zero eigenvalue. There exists one optimal combination of block size and number of blocks at which the time for eigenvalue computation is minimum. These parameters have different effects for different cases. The block Davidson algorithm has also been incorporated with the locking mechanism and this implementation is found to be much superior to its counterpart without the locking mechanism for matrices which have at least one zero eigenvalue.by Vignesh Peruvamba Sundaresh.S.M

Analysis of Envelope Glycoprotein Complex of Arenaviruses

Arenaviruses, the causative agents of severe hemorrhagic fevers, are endemic in rodent populations and can be transmitted to humans by contact. Without effective treatment or licensed vaccines, these viruses pose serious public health and biodefense concern. The sole treatment option is the off-label use of the nucleoside analog ribavirin, which is effective only when given at an early stage of infection and shows significant toxicity in humans. Hence, there exists a clear need for developing better therapies. Arenavirus entry into the cell is initiated by the virus envelope glycoprotein complex (GPC), primed to undergo conformational changes triggered by the acidic pH of the maturing endosome, leading to virus and endosomal membrane fusion. Thus, GPC represents as an important molecular target for therapeutic intervention. Recently, several chemically diverse small-molecule fusion inhibitors were identified that block virus entry by stabilizing the prefusion form of GPC against pH-activation. Improved structural and mechanistic understanding of pH-dependent membrane fusion will advance the design and development of potent inhibitors. Here we report that recombinant native-like GPC can be expressed and purified from insect cells, and mediate pH-dependent membrane fusion when reconstituted into proteoliposomes. This fusion reaction is inhibited by small-molecule fusion inhibitors. Further, I show the first physical evidence of binding of small-molecule inhibitors to the pH-sensitive SSP-GP2 interface using photoreactive inhibitors. In addition, I explored mechanism of pH-induced activation of membrane fusion in Old World Lassa virus (LASV). Although the pH-induced activation mechanism is similar to the well-studied New World Junφn virus (JUNV), the differences lie in the usage of an additional secondary (LAMP1) receptor for LASV entry. Another antiviral strategy is to block the packaging and release of virus particles from an infected host cell. Studies have shown that the viral matrix protein Z plays a critical role in virus assembly and budding. Additionally, accumulation of Z at the plasma membrane and interaction with GPC and nucleoprotein (NP) is thought to orchestrate the assembly and budding events. The assembly process involving interaction of GPC with Z has not been clearly understood. I explored the use of confocal microscopy approach to study the association of GPC and Z at the plasma membrane during assembly of the virus

In Whose Interests Should a Company be Run? Fiduciary Duties of Directors During Corporate Failure in India: Looking to the West for Answers

This Comment looks at the debate as it has played out in the legal jurisprudence of the U.S. and the U.K. The analysis of each considers the three financial stages of a corporation’s existence that are specifically addressed in the debate today, i.e.: (i) solvency; (ii) insolvency; and (iii) the zone of insolvency. After setting out the current position, this Comment specifically addresses the various shortcomings and criticisms of the models adopted by each jurisdiction and offers observations on the status quo and the implementation of these models. On this basis, this Comment goes on to propose a model to be adopted by India, the Indian legal jurisprudence in this respect still being in its evolutionary stages and lacking the depth and the level of analysis found in the West

Differentiation of Human Embryonic Stem Cells to Sympathetic Neurons: A Potential Model for Understanding Neuroblastoma Pathogenesis

Background and Aims: Previous studies modelling human neural crest differentiation from stem cells have resulted in a low yield of sympathetic neurons. Our aim was to optimise a method for the differentiation of human embryonic stem cells (hESCs) to sympathetic neuron-like cells (SN) to model normal human SNS development. Results: Using stromal-derived inducing activity (SDIA) of PA6 cells plus BMP4 and B27 supplements, the H9 hESC line was differentiated to neural crest stem-like cells and SN-like cells. After 7 days of PA6 cell coculture, mRNA expression of SNAIL and SOX-9 neural crest specifier genes and the neural marker peripherin (PRPH) increased. Expression of the pluripotency marker OCT 4 decreased, whereas TP53 and LIN28B expression remained high at levels similar to SHSY5Y and IMR32 neuroblastoma cell lines. A 5-fold increase in the expression of the catecholaminergic marker tyrosine hydroxylase (TH) and the noradrenergic marker dopamine betahydroxylase (DBH) was observed by day 7 of differentiation. Fluorescence-activated cell sorting for the neural crest marker p75, enriched for cells expressing p75, DBH, TH, and PRPH, was more specific than p75 neural crest stem cell (NCSC) microbeads. On day 28 post p75 sorting, dual immunofluorescence identified sympathetic neurons by PRPH and TH copositivity cells in 20% of the cell population. Noradrenergic sympathetic neurons, identified by copositivity for both PHOX2B and DBH, were present in 9.4% ± 5.5% of cells. Conclusions: We have optimised a method for noradrenergic SNS development using the H9 hESC line to improve our understanding of normal human SNS development and, in a future work, the pathogenesis of neuroblastoma

Analysis And Mitigation Of Edge Stresses In Multi-Directional Fiber Reinforced Composite Laminates

Edge delamination in composite laminates with adjacent layers oriented at different fiber angles is a major failure mode because of the existence of high interlaminar stresses and poor interlaminar properties. Mitigation of edge stresses poses a challenge even to date. This research provides a detailed analysis and a potential approach to solve this problem in a carbon/epoxy composite laminate. Two extreme laminates of stacking sequence (0n/90n)s and (+45n/-45n)s subjected to separately applied tensile and thermal loading were considered. These problems have been treated in the literature as a mathematical or bare interface model, wherein the material properties jumped between the adjacent layers of different fiber orientations. A microscopic analysis of laminate cross section showed that the interface was not really bare but there was a thin resin layer of thickness of about 5.0% of the ply thickness. This realization completely changed the modeling and potential modification of the interphase. The region between the plies was represented by a resin layer interphase. A three-dimensional composite finite element (FE) analysis was performed using ANSYS version 12 code. The FE modeling and analysis were verified with the literature for both (0/90)s and (+45/- 45)s laminates for axial tensile loading as well as temperature change. The resin interphase layer with thicknesses of 2.5%, 5.0% and 7.5% of the ply thickness were modeled using three different material properties representing: elastic (brittle epoxy), elastic-plastic (toughened epoxy) and non-linear (interleaved polymer nanofiber composite). As the layer thickness became zero, the bare interface results were recovered. Then, for non-linear resin layer the edge stresses reduced indicating that the interleaving of interphase region had a potential to mitigate edge stresses and thus the edge delamination failure