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.     

Deep Drawing of Friction Stir Welded Thin Sheet Aluminium Steel Tailored Hybrids

Friction stir welding undergoes a steep evolution in industrial applications since the invention in the early 1990s. Especially for aluminium alloys in sheet thicknesses over 2 mm a lot of applications are established, whereas a lack in knowledge about friction stir welding of thin sheets with sheet thickness less than 2 mm exists. This article deals with friction stir welding of thin sheet aluminium steel tailored hybrids and their formability. These investigations tend to close the gap of availability of friction stir welded blanks in the range of 1 mm sheet thickness and to offer new applications of this joining technology. For production of aluminium steel tailored hybrids AA5182 with a thickness of 1.2 mm and DC04 in 1.0 mm are used, the joining partners are friction stir welded in a lap joint. Different tool geometries and process parameters are performed to achieve the highest strength and elongation at fracture of the tailored hybrids. The influence of the stirring on the arrangement and distribution of both materials in the welding zone and its microstructure is analysed using light optical and scanning electron microscopy. In addition to tensile tests planar microhardness measurements help to detect the local changes of the mechanical properties in the characteristic zones of the weld seam. Tailored hybrids, which were friction stir welded with the best welding parameters in accordance to the mechanical properties of the weld seams, were used for deep drawing tests of friction stir welded thin sheet aluminium steel tailored hybrids. The maximum drawing ratio of these tailored hybrids coincides with the one of the parent material of AA5182.     

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.     

Feeding an enhanced diet to Holstein heifers during the preweaning period alters steroid receptor expression and increases cellular proliferation

Preweaning diet and estradiol treatment alters mammary development. Our objectives were to study the effects of diet and estradiol on proliferation of mammary epithelial cells and expression of estrogen receptor α (ESR1) and progesterone receptors (PGR) in these cells. Thirty-six Holstein heifer calves were raised on (1) a control milk replacer fed at 0.44 kg of powder/head per day, dry matter (DM) basis (restricted, R; 20.9% crude protein, 19.8% fat, DM basis), or (2) an enhanced milk replacer fed at 1.08 kg of powder/head per day, DM basis (Enhanced, EH; 28.9% crude protein, 26.2% fat, DM basis). Milk replacer was fed for 8 wk. At weaning, a subset (n = 6/diet) of calves were euthanized and had tissue harvested. Remaining calves received estradiol implants (E₂) or placebo and were euthanized at wk 10 to harvest tissue. Treatments were (1) R, (2) R + E₂ (R-E2), (3) EH, and (4) EH + E₂ (EH-E2). One day before euthanasia calves were given bromo-2′-deoxyuridine (BrdU; 5 mg/kg of body weight). At euthanization, mammary parenchyma was removed and fixed. Tissue sections from zone 1 (cisternal), 2 (medial), and 3 (distal) within the mammary gland were stained with hematoxylin and eosin and antibodies to measure expression of ESR1, PGR, and incorporation of BrdU. At wk 8, R-fed calves had more PGR-expressing cells in distal parenchyma; however, PGR expression intensity was greater in EH-fed calves. The proportion of cells expressing ESR1 was not affected by diet, but expression intensity (receptors per positive cell) was greater in EH-fed calves across all zones (62–81%). Overall, the percent BrdU-positive epithelial cells was 2 and 0.5 fold greater for EH-fed calves in zone 2 and 3. The proportion of labeled cells was greater in terminal ductal units than in subtending ducts, and treatment effects were more evident in terminal ductal units. At wk 10, calves treated with estradiol had 3.9-fold greater PGR expression intensity. The intensity and percent of cells expressing ESR1 was lowest in estradiol-treated calves. Overall, estradiol-treated calves had the greatest number of proliferating epithelial cells. Moreover, in zone 3, EH-E2 calves had a higher percentage of proliferating cells than in all other treatments. Results indicate both diet and estradiol administration alter proliferation rates of the mammary epithelium and that changes in expression of ESR1 and PGR are involved in enhanced mammary development. The data support our hypothesis that enhanced preweaning feeding increases the mammary tissue responsiveness to mammogenic stimulation.