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981.
982.
I was thinking about my philosophical work and saying to myself: 'I destroy, I destroy, I destroy…'
Context: The 'linguistic turn' of Western philosophy (Heidegger's later works, the penetration of Anglo-American philosophies into European thought, the development of language technologies); and correlatively, the decline of universalist discourses (the metaphysical doctrines of modern times: narratives of progress, of socialism, of abundance, of knowledge). The weariness with regard to 'theory', and the miserable slackening that goes along with it (new this, new that, post-this, post-that, etc.). The time has come to philosophize.
…there is no danger of philosophy's 'coming to an end'. Religion did not come to an end in the Enlightenment, nor painting in Impressionism. Even if the period from Plato to Nietzsche is encapsulated and 'distanced' in the way Heidegger suggests, and even if twentieth-century philosophy comes to seem a stage of awkward transitional backing and filling (as sixteenth-century philosophy now seems to us), there will be something called 'philosophy' on the other side of the transition.  相似文献   
983.
We present a simple microchip device consisting of an overlaid pattern of micromagnets and microwells capable of capturing magnetically labeled cells into well-defined compartments (with accuracies >95%). Its flexible design permits the programmable deposition of single cells for their direct enumeration and pairs of cells for the detailed analysis of cell-cell interactions. This cell arraying device requires no external power and can be operated solely with permanent magnets. Large scale image analysis of cells captured in this array can yield valuable information (e.g., regarding various immune parameters such as the CD4:CD8 ratio) in a miniaturized and portable platform.The emergent need for point-of-care devices has spurred development of simplified platforms to organize cells across well-defined templates.1 These devices employ passive microwells, immunospecific adhesive islands, and electric, optical, and acoustic traps to manipulate cells.2–6 In contrast, magnetic templating can control the spatial organization of cells through its ability to readily program ferromagnetic memory states.7 While it has been applied to control the deposition of magnetic beads,8–13 it has not been used to direct the deposition of heterogeneous cell pairs, which may help provide critical insight into the function of single cells.14,15 As such, we developed a simple magnetographic device capable of arraying single cells and pairs of cells with high fidelity. We show this magnetic templating tool can use immunospecific magnetic labels for both the isolation of cells from blood and their organization into spatially defined wells.We used standard photolithographic techniques to fabricate the microchips (see supplementary material16). Briefly, an array of 10 × 30 μm cobalt micromagnets were patterned by a photolithographic liftoff process and overlaid with a pattern of dumbbell-shaped microwells formed in SU-8 photoresist (Fig. 1(a)). The micromagnets were designed to produce a predominantly vertical field in the microwells by aligning the ends of the micromagnet at the center of each well of the dumbbell. These features were deposited across an area of ≈400 mm2 (>50 000 well pairs per microchip) (Fig. 1(b)). Depending on the programmed magnetization state with respect to the external field, magnetic beads or cells were attracted to one pole and repelled by the other pole of each micromagnet, leading to a biased deposition (Fig. 1(c)).12Open in a separate windowFIG. 1.Magnetographic array for single cell analysis. (a) SEM image of the dumbbell-shaped well pairs for capturing magnetically labelled cells. (b) Photograph of the finished device. (c) An array of well pairs displaying a pitch of 60 × 120 μm before (top) and 10 min after the deposition of magnetic beads (bottom).To demonstrate the capability of the array to capture cells into a format amenable for rapid image processing, we organized CD3+ lymphocytes using only hand-held permanent magnets. We isolated CD3+ lymphocytes from blood via positive selection using anti-CD3 magnetic nanoparticles (EasySep™, STEMCELL Technologies) with purities confirmed by flow cytometry (97.8%; see supplementary material16). We then stained 1 × 106 CD3+ cells with anti-CD8 Alexa-488 and anti-CD4 Alexa-647 (5 μl of each antibody in 100 μl for 20 min; BD Bioscience) to determine the CD4:CD8 ratio, a prognostic ratio for assessing the immune system.17,18Variably spaced neodymium magnets (0.5 in. × 0.5 in. × 1 in.; K&J Magnetics, Inc.) were fixed on either side of the microchip to generate a tunable magnetic field (0–400 G; Fig. 2(a)). Using this setup, fluorescently labeled cells were deposited, and the populations of CD4+ and CD8+ cells were indiscriminately arrayed, imaged, and enumerated using ImageJ. The resulting CD4:CD8 ratio of 1.84 ± 0.18 (Fig. 2(b)) was confirmed by flow cytometry with a high correlation (5.4% difference; Fig. 2(c)), indicating the magnetographic microarray can pattern cells for the rapid and accurate assessment of critical phenotypical parameters without complex equipment (e.g., function generators or flow cytometers).Open in a separate windowFIG. 2.CD8 analysis of CD3+ lymphocytes. (a) Photograph of the magnetographic device activated by permanent magnets (covered with green tape). The CD4:CD8 ratio determined by the (b) magnetographic microarray and (c) and (d) flow cytometry was 1.84 and 1.74, respectively.More complex operations, such as the programmed deposition of cell pairs, can be achieved by leveraging the switchable, bistable magnetization of the micromagnets for the detailed studies of cell-cell interactions (Figs. 3(a)–3(d)).12 For these studies, a 200 G horizontal field generated from an electromagnetic coil was used to magnetize the micromagnets.19 We then captured different concentrations of magnetic beads as surrogates for cells (8.4 μm polystyrene, Spherotech, Inc.) and found that higher bead concentrations did not affect the capture accuracy (>95%; see supplementary material16).Open in a separate windowFIG. 3.Programmed pairing of magnetic beads and CD3+ lymphocytes. (a) Schematic of the magnetographic cell pair isolations. (b) Polarized micromagnets isolate cells of one type to one side in a vertical magnetic field and then cells of a second type to the other side when the field is reversed. (c) Fluorescent image of magnetically trapped green stained (top) and red stained (bottom) cell pairs. (d) SEM image of magnetically labeled cells in the microwells. (e) Capture accuracy of magnetic bead pairs. (Each color (and shape) represents the field strength of the reversed field.) (f) Change in the capture accuracy (loss) of initially captured beads after reversing the magnetic field. The capture accuracy of (g) magnetically labeled cell pairs and (h) the second magnetically labeled cell (for (e)–(h): n = 5; time starts from the deposition of the second set of cells or beads).The opposite side of each micromagnet was then populated with the second (yellow fluorescent) bead by reversing the direction of the applied magnetic field. We tested several field strengths (i.e., 10, 25, 40, or 55 G) to optimize the conditions for isolating the desired bead in the opposite well without ejecting the first bead. If the field strength was too large, the previously deposited beads could be ejected from their wells due to the repulsive magnetic force overcoming gravity.12 As shown in Figure 3(e), increasing the field strength from 10 to 25 G significantly increased the capture accuracy at 60 min from the deposition of the second bead (p < 0.01), but increases from 25 to 55 G did not affect the capture accuracy (p > 0.10). As shown in Figure 3(f), higher field strengths (i.e., 40 and 55 G) resulted in lower capture accuracies compared to lower field strengths (i.e., 10 and 25 G) (p < 0.01), which was primarily due to ejection of the initially captured beads when the micromagnets reversed their polarity.We then arranged pairs of membrane dyed (calcein AM, Invitrogen; PKH26, Sigma) magnetically labeled CD3+ lymphocytes. First, red stained cells (150 μl of 2 × 104 cells/ml) were deposited on the microchip in the presence of 250 G vertical magnetic field. After 20 min, the field was reversed (i.e., to 40, 55, and 70 G) and green stained cells (150 μl of 2 × 104 cells/ml) were deposited on the microchip with images taken in 10 min intervals. Fluorescence images were overlaid (Fig. 3(c)) and the capture accuracy of cell pairs was determined (ImageJ).As seen in Figure 3(g), the capture accuracy of pairs of CD3+ lymphocytes was lower than that of magnetic beads (Fig. 3(e)). However, as shown in Figure 3(h), the second set of cells (green fluorescent) exhibited an average capture accuracy of 91.8% ± 1.9%. This indicates that the lower capture accuracy of cell pairs was either due to the ejection of initially captured (red fluorescent) cells or the migration of initially captured cells through the connecting channel, resulting from their relatively high deformability compared to magnetic beads.In summary, we developed a simple device capable of organizing magnetic particles, cells, and pairs of cells into well-defined compartments. A major advantage of this system is the use of specific magnetic labels to both isolate cells and program their deposition. While the design of this device does not enable dynamic control of the spacing between captured cell pairs as does some dielectrophoresis-based devices,20 it can easily capture cells with high fidelity using only permanent magnets and has clinical relevance in the assessment of immune parameters. These demonstrations potentiate a relatively simple and robust device where highly organized spatial arrangement of cells facilitates rapid and accurate analyses towards a functional and low-cost point-of-care device.  相似文献   
984.
Largely due to technological advances, methods for analyzing readability have increased significantly in recent years. While past researchers designed hundreds of formulas to estimate the difficulty of texts for readers, controversy has surrounded their use for decades, with criticism stemming largely from their application in creating new texts as well as their utilization of surface-level indicators as proxies for complex cognitive processes that take place when reading a text. This review focuses on examining developments in the field of readability during the past two decades with the goal of informing both current and future research and providing recommendations for present use. The fields of education, linguistics, cognitive science, psychology, discourse processing, and computer science have all made recent strides in developing new methods for predicting the difficulty of texts for various populations. However, there is a need for further development of these methods if they are to become widely available.  相似文献   
985.
986.
This qualitative research report adopts a critical pedagogy perspective to examine the provision of classroom accommodations for postsecondary students with learning disabilities. Although instructors in the United States are bound to abide by disability rights laws, we also believe instructors can act in ways that allow students to feel comfortable in disclosing their disabilities and in requesting and accessing accommodations for these disabilities. We engaged the voices of 10 university students living with learning disabilities through a series of semi‐structured interviews. These students offered a variety of statements on the ways that their disabilities were accommodated or not by their instructors. We classified these perceptions into three kinds of accommodation perceived by university students with learning disabilities: non‐accommodation, formal accommodation and accommodation for all students. We discuss the implications that these types of accommodations have for pedagogy and offer recommendations for effective techniques for accommodating for all. We hope the voices of these students will serve to enhance communication between students with learning disabilities and their professors.  相似文献   
987.
Abstract

The purpose of this study was to establish if vertical stiffness was greater in professional Australian rules footballers who sustained a lower limb skeletal muscle strain compared to those who did not, and to establish if a relationship between age, or training history, and vertical stiffness existed. Thirty-one participants underwent weekly rebound jump testing on a force platform over two seasons. Vertical stiffness was calculated for injured players and the uninjured cohort 1 and 3 weeks prior to sustaining an injury and at the end of preseason. Eighteen athletes were in the “uninjured” cohort and 13 in the “injured” cohort. No significant difference in vertical stiffness was observed between groups (P = 0.18 for absolute stiffness; P = 0.08 for stiffness relative to body mass), within groups (P = 0.83 and P = 0.88, respectively) or for a time*cohort interaction (P = 0.77 and P = 0.80, respectively). No relationship between age and vertical stiffness existed (r = ?0.06 for absolute and relative stiffness), or training history and vertical stiffness (r = ?0.01 and 0.00 for absolute and relative stiffness, respectively) existed. These results and others lend to suggest that vertical stiffness is not related to lower limb muscle strain injury.  相似文献   
988.
989.
Students with disabilities often take tests under different conditions than their peers do. Testing accommodations, which involve changes to test administration that maintain test content, include extending time limits, presenting written text through auditory means, and taking a test in a private room with fewer distractions. For some students with disabilities, accommodations such as these are necessary for fair assessment; without accommodations, invalid interpretations would be made on the basis of these students’ scores. However, when misapplied, accommodations can also diminish fairness, introduce new sources of construct-irrelevant variance, and also lead to invalid interpretation of test scores. This module provides a psychometric framework for thinking about accommodations, and then explicates an accommodations decision-making framework that includes a variety of considerations. Problems with current accommodations practices are discussed, along with potential solutions and future directions. The module is accompanied by exercises allowing participants to apply their understanding.  相似文献   
990.
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