957 resultados para SMALL MOLECULES
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Purpose To explore the effect of small-aperture optics, designed to aid presbyopes by increasing ocular depth-of-focus, on measurements of the visual field. Methods Simple theoretical and ray-tracing models were used to predict the impact of different designs of small-aperture contact lenses or corneal inlays on the proportion of light passing through natural pupils of various diameters as a function of the direction in the visual field. The left eyes of five healthy volunteers were tested using three afocal, hand-painted opaque soft contact lenses (www.davidthomas.com). Two were opaque over a 10 mm diameter but had central clear circular apertures of 1.5 and 3.0 mm in diameter. The third had an annular opaque zone with inner and outer diameters of 1.5 and 4.0 mm, approximately simulating the geometry of the KAMRA inlay (www.acufocus.com). A fourth, clear lens was used for comparison purposes. Visual fields along the horizontal meridian were evaluated up to 50° eccentricity with static automated perimetry (Medmont M700, stimulus Goldmann-size III; www.medmont.com). Results According to ray-tracing, the two lenses with the circular apertures were expected to reduce the relative transmittance of the pupil to zero at specific field angles (around 60° for the conditions of the experimental measurements). In contrast, the annular stop had no effect on the absolute field but relative transmittance was reduced over the central area of the field, the exact effects depending upon the natural pupil diameter. Experimental results broadly agreed with these theoretical expectations. With the 1.5 and 3.0 mm pupils, only minor losses in sensitivity (around 2 dB) in comparison with the clear-lens case occurred across the central 10° radius of field. Beyond this angle, sensitivity losses increased, to reach about 7 dB at the edge of the measured field (50°). The field results with the annular stop showed at most only a slight loss in sensitivity (≤3 dB) across the measured field. Conclusion The present theoretical and experimental results support earlier clinical findings that KAMRA-type annular stops, unlike circular artificial pupils, have only minor effects on measurements of the visual field.
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As tumors grow larger, they often experience an insufficient supply of oxygen and nutrients. Hence, cancer cells must develop mechanisms to overcome these stresses. Using an in vitro transformation model where the presence of the simian virus 40 (SV40) small T (ST) antigen has been shown to be critical for tumorigenic transformation, we investigated whether the ST antigen has a role to play in regulating the energy homeostasis of cancer cells. We find that cells expressing the SV40 ST antigen (+ST cells) are more resistant to glucose deprivation-induced cell death than cells lacking the SV40 ST antigen (-ST cells). Mechanistically, we find that the ST antigen mediates this effect by activating a nutrient-sensing kinase, AMP-activated protein kinase (AMPK). The basal level of active, phosphorylated AMPK was higher in +ST cells than in -ST cells, and these levels increased further in response to glucose deprivation. Additionally, inhibition of AMPK in +ST cells increased the rate of cell death, while activation of AMPK in -ST cells decreased the rate of cell death, under conditions of glucose deprivation. We further show that AMPK mediates its effects, at least in part, by inhibiting mTOR (mammalian target of rapamycin), thereby shutting down protein translation. Finally, we show that +ST cells exhibit a higher percentage of autophagy than -ST cells upon glucose deprivation. Thus, we demonstrate a novel role for the SV40 ST antigen in cancers, where it functions to maintain energy homeostasis during glucose deprivation by activating AMPK, inhibiting mTOR, and inducing autophagy as an alternate energy source.
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By using a perturbation technique, the Korteweg-de Vries equation is derived for a mixture of warm-ion fluid and hot, isothermal electrons. Stationary solutions are obtained for this equation and are compared with the corresponding solutions for a mixture consisting of cold-ion fluid and hot, isothermal electrons.
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The adequacy and efficiency of existing legal and regulatory frameworks dealing with corporate phoenix activity have been repeatedly called into question over the past two decades through various reviews, inquiries, targeted regulatory operations and the implementation of piecemeal legislative reform. Despite these efforts, phoenix activity does not appear to have abated. While there is no law in Australia that declares ‘phoenix activity’ to be illegal, the behaviour that tends to manifest in phoenix activity can be capable of transgressing a vast array of law, including for example, corporate law, tax law, and employment law. This paper explores the notion that the persistence of phoenix activity despite the sheer extent of this law suggests that the law is not acting as powerfully as it might as a deterrent. Economic theories of entrepreneurship and innovation can to some extent explain why this is the case and also offer a sound basis for the evaluation and reconsideration of the existing law. The challenges facing key regulators are significant. Phoenix activity is not limited to particular corporate demographic: it occurs in SMEs, large companies and in corporate groups. The range of behaviour that can amount to phoenix activity is so broad, that not all phoenix activity is illegal. This paper will consider regulatory approaches to these challenges via analysis of approaches to detection and enforcement of the underlying law capturing illegal phoenix activity. Remedying the mischief of phoenix activity is of practical importance. The benefits include continued confidence in our economy, law that inspires best practice among directors, and law that is articulated in a manner such that penalties act as a sufficient deterrent and the regulatory system is able to detect offenders and bring them to account. Any further reforms must accommodate and tolerate legal phoenix activity, at least to some extent. Even then, phoenix activity pushes tolerance of repeated entrepreneurial failure to its absolute limit. The more limited liability is misused and abused, the stronger the argument to place some restrictions on access to limited liability. This paper proposes that such an approach is a legitimate next step for a robust and mature capitalist economy.
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This thesis consists of two parts; in the first part we performed a single-molecule force extension measurement with 10kb long DNA-molecules from phage-λ to validate the calibration and single-molecule capability of our optical tweezers instrument. Fitting the worm-like chain interpolation formula to the data revealed that ca. 71% of the DNA tethers featured a contour length within ±15% of the expected value (3.38 µm). Only 25% of the found DNA had a persistence length between 30 and 60 nm. The correct value should be within 40 to 60 nm. In the second part we designed and built a precise temperature controller to remove thermal fluctuations that cause drifting of the optical trap. The controller uses feed-forward and PID (proportional-integral-derivative) feedback to achieve 1.58 mK precision and 0.3 K absolute accuracy. During a 5 min test run it reduced drifting of the trap from 1.4 nm/min in open-loop to 0.6 nm/min in closed-loop.
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Small, not-for-profit organisations fulfil a need in the economy that is typically not satisfied by for-profit firms. They also operate in ways that are distinct from larger organisations. While such firms employ a substantial proportion of the workforce, research addressing human resource management (HRM) practices in these settings is limited. This article used data collected from five small not-for-profit firms in Australia to examine the way one significant HRM practice – the provision and utilisation of flexible work arrangements – operates in the sector. Drawing on research from several scholarly fields, the article firstly develops a framework comprising three tensions in not-for-profits that have implications for HRM. These tensions are: (1) contradictions between an informal approach to HRM vs. a formal regulatory system; (2) employee values that favour social justice vs. external market forces; and (3) a commitment to service vs. external financial expectations. The article then empirically examines how these tensions are managed in relation to the specific case of flexible work arrangements. The study reveals that tensions around providing and accessing flexible work arrangements are managed in three ways: discretion, leadership style and distancing. These findings more broadly inform the way HRM is operationalised in this under-examined sector.