Microfluidic immobilization and subcellular imaging of developing <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis>

Caenorhabditis elegans has been an essential model organism in the fields of developmental biology, neuroscience, and aging. However, these areas have been limited by our ability to visualize and track individual C. elegans worms, especially at the subcellular scale, over the course of their lifetime. Here we present a microfluidic device to culture individual C. elegans in parallel throughout post-embryonic development. The device allows for periodic mechanical immobilization of the worm, enabling 3D imaging at subcellular precision. The immobilization is sufficient to enable fluorescence recovery after photobleaching (FRAP) measurements on organelles and other substructures within the same specific cells throughout larval development, without the use of chemical anesthetics. Using this device, we measure FRAP recovery of two nucleolar proteins in specific intestinal cells within the same worms during larval development. We show that these proteins exhibit different fluorescence recovery as the worm grows, suggesting differential protein interactions during development. We anticipate that this device will help expand the possible uses of C. elegans as a model organism, enabling its use in addressing fundamental questions at the subcellular scale.     

Oscillatory Metastability in Optical Network Synchronizer Circuits

Synchronization of signal packets is required in networks in order to route the packets. Due to changes in the interarrival times of the packets the inputs to the routing circuits may exhibit oscillatory metastability. Oscillatory metastability can be eliminated in optical circuits by the addition of logic signal stretch. This can be done because the propagation time of optics can be precisely controlled. An algorithm for inserting logic signal stretch to eliminate oscillatory metastability is presented herein.     

One-dimensional axial simulation of electric double layer overlap effects in devices combining micro- and nanochannels

This paper presents a numerical steady-state model of ion transport in micro- and nanofluidic devices with widely varying geometric scale, such as transitions between micro- and nanochannels. Finite element or finite volume simulation of such problems is challenging, due to the number of elements needed to produce a satisfactory mesh. Here, only the lengthwise channel dimension is meshed; standard analytical approximations are used to incorporate cross-channel properties. Singularly perturbed cases are built up by continuation. The method is shown to reproduce our previously reported measurements of electric double-layer effects on conductivity, ion concentration, and ion enhancement and depletion. Comparison with 2-D simulations reported in the literature shows that effects on accuracy due to the 1-D approximation are small. The model incorporates analytical models of surface charge density taken from the literature. This enables predictive simulation with reasonable accuracy using published parameter values, or these values may be tuned based on experiment to give improved results. Use of the model for iterative design and parameter estimation is demonstrated.     

The Epigenesis of Meaning in Human Beings,and Possibly in Robots

Minds and Machines - This article addresses a classical question: Can a machine use language meaningfully and if so, how can this be achieved? The first part of the paper is mainly philosophical....     

Development of clinical indicators for performance measurement and improvement: an HMO/purchaser collaborative effort

This article describes a collaborative effort between a major health care purchaser, three area health maintenance organizations, and a state Medicaid agency to develop clinical indicators as the basis for a comparison database. Some of the difficulties in developing a "common yardstick" of quality and value are candidly discussed.     

Cardiac transplantation in perspective for the future. Survival, complications, rehabilitation, and cost

Two hundred twenty-seven cardiac transplant procedures have been performed in 206 patients from January, 1968, to April, 1981. Postoperative survival rates, calculated by the actuarial method for program years 1968 to 1973 (66 patients), are 44%, 33%, 27%, 21%, and 18% at 1, 2, 3, 4, and 5 years after transplantation, respectively. Postoperative survival rates for program years 1974 to 1981 (140 patients) are 63%, 55%, 51, 44%, and 39% at 1, 2, 3, 4, and 5 years after transplantation, respectively. This increase results primarily from improvement in survival achieved in the first 3 postoperative months (59% +/- 7%, 1968 to 1973, versus 80% +/- 40%, 1974 to 1980), reflecting improved patient management. Infection remains the primary cause of death following transplantation (76/131 patients, 58%), followed by acute rejection (24/181, 18.3%), graft arteriosclerosis (14/131, 10.7%), and malignancy (6/131, 4.6%). The development of graft arteriosclerosis has been examined in 85 one-year survivors studied by annual coronary arteriograms. Coronary lesions of varying severity have developed in 21 patients. HLA-A2 incompatibility was associated with a higher incidence of graft arteriosclerosis than was apparent for all other A locus incompatibilities (p less than 0.0003). Lymphoma has been shown to be associated with younger recipient age, a primary disease diagnosis of idiopathic cardiomyopathy, and retransplantation. One hundred six patients have survived at least 1 year after transplantation; 97% were in NYHA Class 1 at that time interval and 82% returned to employment or activity of choice. The longest survival time is new 11 years, 3 months. Cardiac transplantation can be considered "reasonable and therapeutic treatment to extend life" in selected individuals.     

Abductive Theorem Proving for Analyzing Student Explanations to Guide Feedback in Intelligent Tutoring Systems

The Why2-Atlas tutoring system presents students with qualitative physics questions and encourages them to explain their answers through natural language. Although there are inexpensive techniques for analyzing explanations, we claim that better understanding is necessary for use within tutoring systems. In this paper we motivate and describe how the system creates and uses a deeper proof-based representation of student essays in order to provide students with substantive feedback on their explanations. We describe in detail the abductive reasoner, Tacitus-lite+, that we use within the tutoring system. We also discuss evaluation results for an early version of the Why2-Atlas system and a subsequent evaluation of the theorem-proving module. We conclude with the discussion of work in progress and additional future work for deriving more benefits from a proof-based approach for tutoring applications.     

Entanglement energetics in the ground state

Abstract

We show how many-body ground state entanglement information may be extracted from sub-system energy measurements at zero temperature. A precise relation between entanglement and energy fluctuations is demonstrated in the weak coupling limit. Examples are given with the two-state system and the harmonic oscillator, and energy probability distributions are calculated. Comparisons made with recent qubit experiments show this type of measurement provides another method to quantify entanglement with the environment.     

Effectiveness of traffic light vs. boom barrier controls at road–rail level crossings: A simulator study

Although collisions at level crossings are relatively uncommon occurrences, the potential severity of their consequences make them a top priority among safety authorities. Twenty-five fully-licensed drivers aged between 20 and 50 years participated in a driving simulator study that compared the efficacy, and drivers’ subjective perception, of two active level crossing traffic control devices: flashing lights with boom barriers and standard traffic lights. Because of its common usage in most states in Australia, a stop sign-controlled level crossing served as the passive referent. Although crossing violations were less likely at the level crossings controlled by active devices than at those controlled by stop signs, both kinds of active control were associated with a similar number of violations. Further, the majority (72%) of drivers reported preferring flashing lights to traffic lights. Collectively, results indicate that the installation of traffic lights at real-world level crossings would not be likely to offer safety benefits over and above those provided already by flashing lights with boom barriers. Furthermore, the high rate of violations at passively controlled crossings strongly supports the continued practice of upgrading level crossings with active traffic control devices.     

Bars on blocks: A cellular automata model of crime and liquor licensed establishment density

Criminologists have extensively researched the problems generated by licensed establishments. Violent offending and disorderly behavior resulting from pubs, taverns, dance clubs and bars are of particular interest to this field of study. The relative density of these liquor establishments has been found to be associated with the level of violence and disorder in surrounding areas. A complex systems approach can be used to further understand the dynamic interplay between licensed establishments, violent offending and disorder, and urban planning decisions. The model presented here utilizes cellular automata as the mathematical framework to view the varying impact of liquor licensing density on crime. This study uses a sample of liquor establishments and crime data from the City of Vancouver in British Columbia. The cellular automata model incorporates transition rules which govern the change of city blocks from low-risk blocks to high-risk blocks. The results represented by a 50 × 50 cellular grid show that high-risk blocks multiply when liquor licenses are grouped. Two scenarios are presented to contrast the impact of grouping high-risk blocks which contain more liquor establishments and dispersing such blocks. A third scenario demonstrates how increasing the positive influence in a grouped scenario stops high-risk blocks from taking over the entire grid. Future iterations of this model will incorporate census data, public transportation data, land use data and entertainment districts from other cities to further analyze the effect of licensed establishments on the distribution of crime.