Numerical methods for the analysis of sampled-data systems and for the computation of system zeros

MARSYAS is a computer-aided control system design package for the simulation and analysis of dynamic systems. In the summer of 1991 MARSYAS was updated to allow for the analysis of sampled-data systems in terms of frequency response, stability, etc. This update was continued during the summer of 1992 in order to extend further MARSYAS commands to the study of sampled-data systems. Further work was done to examine the computation of OPENAT transfer functions, root-locii and w-plane frequency response plots

Lehrer(innen)mangel und Lehrer(innen)arbeitslosigkeit in den bernischen Primarschulen zwischen 1900 und 1945

Die Geschichte des bernischen Primarschulwesem im 20. Jahrhundert ist mitgeprägt von mehreren Zyklen des LehrerInnenmangels und der LehrerInnenarbeitslosigkeit, die auf vielschichtigen Ursachenfaktoren mit einer hohen Eigendynamik basieren. Ein gewichtiger Stellenwert muss jedoch auch den politischen Steuerungsversuchen beigemessen werden, die bisher zu stark auf die Bewältigung der jeweils gerade aktuellen Problemlage fixiert gewesen sind und dadurch eher zu einer Verschärfung anstatt zu einer Dämpfung der nachfolgenden Phase beigetragen haben. nIm folgenden Artikel werden die Veränderungen zwischen 1900 und 1945 zusammenfassend dargestellt, die einen Einblick vermitteln in teilweise fragwürdige bildungspolitische Massnahmen, von denen insbesonders verheiratete Lehrerinnen und ausserkantonale Lehrkräfte, aber auch Jugendliche betroffen waren, deren Zugangschancen zur LehrerInnenausbildung bis heute unabhängig von ihrer Qualifikation je nach Stellenlage sehr unterschiedlich sind

Financial Liberalization and Money Demand in Mauritius

2 Financial Liberalization and Money Demand in Mauritius Abstract The Bank of Mauritius is considering moving to a formal inflation-targeting framework, which will require, among other things, a better understanding of the monetary policy transmission mechanism. This paper will contribute to this understanding by testing the stability of the money demand function for both M1 and M2 in Mauritius using annual data for the period 1967 to 2005. The Durbin h test and Chow test for structural stability are employed to ascertain whether the current policy framework satisfies the necessary condition for effectiveness. The results demonstrate a stable money demand function

Arhangel'skiĭ's solution to Alexandroff's problem: A survey

AbstractIn 1969, Arhangel'skiĭ proved that |X|⩽2χ(X)L(X) for every Hausdorff space X. This beautiful inequality solved a nearly fifty-year old question raised by Alexandroff and Urysohn. In this paper we survey a wide range of generalizations and variations of Arhangel'skiĭ's inequality. We also discuss open problems and an important legacy of the theorem: the emergence of the closure method as a fundamental unifying device in cardinal functions

Nanoscale study of perforin pore formation and lipid specificity

Perforin is a key effector protein of the vertebrate immune system. Secreted as soluble monomers by cytotoxic T lymphocytes and natural killer cells, perforin selectively forms oligomeric transmembrane pore assemblies on the surface of virus infected and cancerous cells. These 10-20 nm wide pores allow diffusion of co-secreted granzymes into the target cells, which next trigger apoptotic cell killing. To understand the pathway of perforin pore assembly on/in target membranes, we have visualised different stages of this process by atomic force and electron microscopy. Initially, perforin forms intermediate, prepore oligomers of up to 8 subunits on the membrane surface. These short oligomers can subsequently convert to membrane pores with a tighter subunit packing. These pore assemblies next recruit further prepore oligomers from the membrane surface to grow the pore size. Most of the resulting arc- and ring-shaped perforin pores contain between 10 - 30 subunits. To identify mechanisms by which immune cells are protected from self-harm by perforin, we have investigated how perforin pore assembly depends on the lipid composition of the target membrane. Perforin binding is affected by the packing density of lipid molecules in the membrane: It does not or hardly binds to raft-like, liquid ordered lipid domains. Furthermore, negatively charged membrane surfaces, i.e., rich in phosphatidylserine, allow perforin binding and oligomerization of short intermediate assemblies, but subsequently trap these assemblies in a non-porating, dysfunctional state. These findings coincide with reports of increased lipid packing and phosphatidylserine exposure on the surface of activated cytotoxic T lymphocytes

How Scared Are You? A Literature Review Contextualizing the Environment of Threats and Harassment of Local Officials in the United States over the Last 10 Years

Targeted threats, harassment, and the perpetration of physical violence against elected officials are becoming increasingly commonplace around the world. Sadly, the United States and our own backyard of San Diego is no exception. Local leaders - the most foundational representatives of the democratic processes that undergird our system of government - are facing unprecedented levels of uncivil and anti-democratic threats, harassment, and attacks. By nearly all measures, political violence is considered to be more acceptable in the U.S. than it was five years ago. Current data indicates that the majority of threatening and harassing behavior directed against local officials is non-physical and occurs through online spaces. However, permissive rhetoric can both harm our democracy as well as escalate into physical violence targeting democratically elected leaders. A high-profile example of this is the brutal attack on Nancy Pelosi’s husband, Paul Pelosi, in October 2022. David DePape broke into the Pelosis’ San Francisco home with the intention of kidnapping the former speaker of the US House. Instead, DePape encountered Paul Pelosi, an 82-year-old man, who he attacked with a hammer. DePape left Pelosi unconscious, with a fractured skull and injuries on his hand and harm. Officials who investigated the attack found that DePape had an extensive history of online engagement with right-wing conspiracy theories and angry rants against women. In his blog, DePape described how Gamergate, an online forum filled with far-right conspiracy theories and violent rhetoric against women, was the catalyst for much of his worldview. Joan Donovan, who recently co-authored a book examining Gamergate’s role in the rise of alt-right political movements, stated that Depape’s move from an online space to an attempted real-world attack on a female public figure is unsurprising. Incidents like this highlight the danger of violent rhetoric leading to physical violence, as well as demonstrate the need for further analysis of the connection between violent political rhetoric and violent outcomes. While high-profile incidents such as the Pelosi attack provide crucial context for the broad scope of threats, harassment, and violence directed at public officials, this literature review will focus on the less prominent, but nonetheless critical, issue of threats and harassment directed at local elected officials. In particular, this literature review centers around school board officials, members of city councils, and mayors located within San Diego County as well as across the United States. The literature review will consider the current research on the scope of the threats and harassment faced by local officials, the drivers of threatening and harassing behavior, and its impacts on local officials and the democratic process. In addition, this literature review will provide an overview of current recommendations for reducing the level of threat to local officials and improving the civil discourse. Finally, the literature review will conclude with recommendations for further research around threats and harassment directed at local officials.https://digital.sandiego.edu/ipj-research/1069/thumbnail.jp

How robust are malaria parasite clearance rates as indicators of drug effectiveness and resistance?

Artemisinin combination therapies (ACTs) are currently the first line drugs for treating uncomplicated falciparum malaria, the most deadly of the human malarias. Malaria parasite clearance rates estimated from patients' blood following ACT treatment have been widely adopted as a measure of drug effectiveness and as surveillance tools for detecting the presence of potential artemisinin drug resistance. This metric has not been investigated in detail, nor have its properties or potential shortcomings been identified. Herein, the pharmacology of drug treatment, parasite biology, and human immunity are combined to investigate the dynamics of parasite clearance following ACT treatment. This approach parsimoniously recovers the principal clinical features and dynamics of clearance. Human immunity is the primary determinant of clearance rates unless, or until, artemisinin killing has fallen to near-ineffective levels. Clearance rates are therefore highly insensitive metrics for surveillance that may lead to over-confidence as even quite substantial reductions in drug sensitivity may not be detected as slower clearance rates. Equally serious is the use of clearance rates to quantify the impact of ACT regime changes as this strategy will plausibly miss even very substantial increases in drug effectiveness. In particular, the malaria community may be missing the opportunity to dramatically increase ACT effectiveness through changes in regimen, particularly through a switch to twice-daily regimens and/or increases in artemisinin dosing levels. The malaria community therefore appears over reliant on a single metric of drug effectiveness, parasite clearance rate that has significant and serious shortcomings

Altering Antimalarial Drug Regimens May Dramatically Enhance and Restore Drug Effectiveness.

There is considerable concern that malaria parasites are starting to evolve resistance to the current generation of antimalarial drugs, the artemisinin-based combination therapies (ACTs). We use pharmacological modeling to investigate changes in ACT effectiveness likely to occur if current regimens are extended from 3 to 5 days or, alternatively, given twice daily over 3 days. We show that the pharmacology of artemisinins allows both regimen changes to substantially increase the artemisinin killing rate. Malaria patients rarely contain more than 10(12) parasites, while the standard dosing regimens allow approximately 1 in 10(10) parasites to survive artemisinin treatment. Parasite survival falls dramatically, to around 1 in 10(17) parasites if the dose is extended or split; theoretically, this increase in drug killing appears to be more than sufficient to restore failing ACT efficacy. One of the most widely used dosing regimens, artemether-lumefantrine, already successfully employs a twice-daily dosing regimen, and we argue that twice-daily dosing should be incorporated into all ACT regimen design considerations as a simple and effective way of ensuring the continued long-term effectiveness of ACTs