Essence and Necessity, and the Aristotelian Modal Syllogistic: A Historical and Analytical Study

The following is a critical and historical account of Aristotelian Essentialism informed by recent work on Aristotle’s modal syllogistic. The semantics of the modal syllogistic are interpreted in a way that is motivated by Aristotle, and also make his validity claims in the Prior Analytics consistent to a higher degree than previously developed interpretative models. In Chapter One, ancient and contemporary objections to the Aristotelian modal syllogistic are discussed. A resolution to apparent inconsistencies in Aristotle’s modal syllogistic is proposed and developed out of recent work by Patterson, Rini, and Malink. In particular, I argue that the semantics of negation is distinct in modal context from those of assertoric negative claims. Given my interpretive model of Aristotle’s semantics, in Chapter Two, I provide proofs for each of the mixed apodictic syllogisms, and propose a method of using Venn Diagrams to visualize the validity claims Aristotle makes in the Prior Analytics. Chapter Three explores how Aristotle’s syllogistic fits within Aristotle’s philosophy of science and demonstration, particularly within the context of the Posterior Analytics. Consideration is given to the Aristotelian understanding of the relationship among necessity, explanation, definition, and essence. Chapter Four applies Aristotelian modal logic in contemporary contexts. I contrast Aristotelian modality and essentialism with contemporary modalism based upon the semantics of possible worlds, e.g. Kripke and Putnam. I also develop an account of how Aristotelian modal logic can ground a sortal dependent theory of identity, as discussed by Wiggins

Microcoining ripples in metal foils

Experiments, upper bound models, and finite element simulations are used to determine forming loads needed to microcoin surface ripples in thin metal foils. Coining is traditionally performed in a closed die, however enclosing all non-patterned surfaces is difficult to directly scale down to sub-millimeter foils. We find different forming regimes can exist at this small scale in an open pressing configuration. We explore the effects of the metal foil thickness and its work hardening behavior, two primary factors controlling the microcoining ripple forming load. For very thin foils, the load needed to coin a ripple pattern is lower than the load needed to compress the foil so that the open pressing configuration behavior is effectively closed with pattern formation without thickness change. For moderate thickness foils, the load needed to coin significantly drops as the entire foil compresses. For thick foils approaching bulk materials, the pattern will not completely form as the die macroscopically indents into the metal. Work hardening is found to raise the forming load for the thin, effectively closed die scenario, however it is a secondary effect at moderate thickness. This insight is used to microcoin patterns in extremely hard, thin metal foils

The Effect of Compositional Context on Synthetic Gene Networks

It is well known that synthetic gene expression is highly sensitive to how genetic elements (promoter structure, spacing regions between promoter and coding sequences, ribosome binding sites, etc.) are spatially configured. An important topic that has received far less attention is how the compositional context, or spatial arrangement, of entire genes within a synthetic gene network affects their individual expression levels. In this paper we show, both quantitatively and qualitatively, that compositional context significantly alters transcription levels in synthetic gene networks. We demonstrate that key characteristics of gene induction, such as ultra-sensitivity and dynamic range, strongly depend on compositional context. We postulate that supercoiling can be used to explain this interference and validate this hypothesis through modeling and a series of in vitro supercoiling relaxation experiments. This compositional interference enables a novel form of feedback in synthetic gene networks. We illustrate the use of this feedback by redesigning the toggle switch to incorporate compositional context. We show the context-optimized toggle switch has improved threshold detection and memory properties

Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915)

Teràpia adjuvant; MelanomaTerapia adyuvante; MelanomaAdjuvant therapy; MelanomaPURPOSE Ipilimumab and nivolumab have each shown treatment benefit for high-risk resected melanoma. The phase III CheckMate 915 trial evaluated adjuvant nivolumab plus ipilimumab versus nivolumab alone in patients with resected stage IIIB-D or IV melanoma. PATIENTS AND METHODS In this randomized, double-blind, phase III trial, 1,833 patients received nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks (916 patients) or nivolumab 480 mg once every 4 weeks (917 patients) for ≤ 1 year. After random assignment, patients were stratified by tumor programmed death ligand 1 (PD-L1) expression and stage. Dual primary end points were recurrence-free survival (RFS) in randomly assigned patients and in the tumor PD-L1 expression-level < 1% subgroup. RESULTS At a minimum follow-up of approximately 23.7 months, there was no significant difference between treatment groups for RFS in the all-randomly assigned patient population (hazard ratio, 0.92; 95% CI, 0.77 to 1.09; P = .269) or in patients with PD-L1 expression < 1% (hazard ratio, 0.91; 95% CI, 0.73 to 1.14). In all patients, 24-month RFS rates were 64.6% (combination) and 63.2% (nivolumab). Treatment-related grade 3 or 4 adverse events were reported in 32.6% of patients in the combination group and 12.8% in the nivolumab group. Treatment-related deaths were reported in 0.4% of patients in the combination group and in no nivolumab-treated patients. CONCLUSION Nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks did not improve RFS versus nivolumab 480 mg once every 4 weeks in patients with stage IIIB-D or stage IV melanoma. Nivolumab showed efficacy consistent with previous adjuvant studies in a population resembling current practice using American Joint Committee on Cancer eighth edition, reaffirming nivolumab as a standard of care for melanoma adjuvant treatment

Barriers to Completing Colonoscopy Screenings

Background: - Colon cancer is the second leading cause of cancer death in the United States and the third leading cause of cancer death in Vermont. - Colon cancer progression may be prevented by removing precancerous polyps found on colonoscopy screening. -Vermont ranks among the states with the best colon cancer screening rates, but there is room for improvement. In 2006, 55.5% of Vermonters over 50 years of age had undergone a sigmoidoscopy or colonoscopy within the last 5 years. Vermont’s public health goal is to raise this percentage of screened individuals to 65% by 2010. - Vermont medical institutions have the resources to perform screening colonoscopies on all Vermonters over 50 years of age. - Although primary care physician (PCP) recommendations increase the likelihood of a patient completing a colonoscopy screening, a substantial number of patients referred for screening colonoscopies do not complete their appointments.https://scholarworks.uvm.edu/comphp_gallery/1004/thumbnail.jp

Inference on inspiral signals using LISA MLDC data

In this paper we describe a Bayesian inference framework for analysis of data obtained by LISA. We set up a model for binary inspiral signals as defined for the Mock LISA Data Challenge 1.2 (MLDC), and implemented a Markov chain Monte Carlo (MCMC) algorithm to facilitate exploration and integration of the posterior distribution over the 9-dimensional parameter space. Here we present intermediate results showing how, using this method, information about the 9 parameters can be extracted from the data.Comment: Accepted for publication in Classical and Quantum Gravity, GWDAW-11 special issu

Biophysical Constraints Arising from Compositional Context in Synthetic Gene Networks

Synthetic gene expression is highly sensitive to intragenic compositional context (promoter structure, spacing regions between promoter and coding sequences, and ribosome binding sites). However, much less is known about the effects of intergenic compositional context (spatial arrangement and orientation of entire genes on DNA) on expression levels in synthetic gene networks. We compare expression of induced genes arranged in convergent, divergent, or tandem orientations. Induction of convergent genes yielded up to 400% higher expression, greater ultrasensitivity, and dynamic range than divergent- or tandem-oriented genes. Orientation affects gene expression whether one or both genes are induced. We postulate that transcriptional interference in divergent and tandem genes, mediated by supercoiling, can explain differences in expression and validate this hypothesis through modeling and in vitro supercoiling relaxation experiments. Treatment with gyrase abrogated intergenic context effects, bringing expression levels within 30% of each other. We rebuilt the toggle switch with convergent genes, taking advantage of supercoiling effects to improve threshold detection and switch stability

The status of GEO 600

The GEO 600 laser interferometer with 600m armlength is part of a worldwide network of gravitational wave detectors. GEO 600 is unique in having advanced multiple pendulum suspensions with a monolithic last stage and in employing a signal recycled optical design. This paper describes the recent commissioning of the interferometer and its operation in signal recycled mode