Growth hormone (GH)–releasing hormone and GH secretagogues in normal aging: Fountain of Youth or Pool of Tantalus?

Although growth hormone (GH) is primarily associated with linear growth in childhood, it continues to have important metabolic functions in adult life. Adult GH deficiency (AGHD) is a distinct clinical entity, and GH replacement in AGHD can improve body composition, strength, aerobic capacity, and mood, and may reduce vascular disease risk. While there are some hormone-related side effects, the balance of benefits and risks is generally favorable, and several countries have approved GH for clinical use in AGHD. GH secretion declines progressively and markedly with aging, and many age-related changes resemble those of partial AGHD. This suggests that replacing GH, or stimulating GH with GH-releasing hormone or a GH secretagogue could confer benefits in normal aging similar to those observed in AGHD – in particular, could reduce the loss of muscle mass, strength, and exercise capacity leading to frailty, thereby prolonging the ability to live independently. However, while most GH studies have shown body composition effects similar to those in AGHD, functional changes have been much less inconsistent, and older adults are more sensitive to GH side effects. Preliminary reports of improved cognition are encouraging, but the overall balance of benefits and risks of GH supplementation in normal aging remains uncertain

Nuclear phytochrome a signaling promotes phototropism in Arabidopsis.

Phototropin photoreceptors (phot1 and phot2 in Arabidopsis thaliana) enable responses to directional light cues (e.g., positive phototropism in the hypocotyl). In Arabidopsis, phot1 is essential for phototropism in response to low light, a response that is also modulated by phytochrome A (phyA), representing a classical example of photoreceptor coaction. The molecular mechanisms underlying promotion of phototropism by phyA remain unclear. Most phyA responses require nuclear accumulation of the photoreceptor, but interestingly, it has been proposed that cytosolic phyA promotes phototropism. By comparing the kinetics of phototropism in seedlings with different subcellular localizations of phyA, we show that nuclear phyA accelerates the phototropic response, whereas in the fhy1 fhl mutant, in which phyA remains in the cytosol, phototropic bending is slower than in the wild type. Consistent with this data, we find that transcription factors needed for full phyA responses are needed for normal phototropism. Moreover, we show that phyA is the primary photoreceptor promoting the expression of phototropism regulators in low light (e.g., PHYTOCHROME KINASE SUBSTRATE1 [PKS1] and ROOT PHOTO TROPISM2 [RPT2]). Although phyA remains cytosolic in fhy1 fhl, induction of PKS1 and RPT2 expression still occurs in fhy1 fhl, indicating that a low level of nuclear phyA signaling is still present in fhy1 fhl

Information on 'overdiagnosis' in breast cancer screening on prominent United Kingdom- and Australia-oriented health websites

Objectives: Health-related websites are an important source of information for the public. Increasing public awareness of overdiagnosis and ductal carcinoma in situ (DCIS) in breast cancer screening may facilitate more informed decision-making. This study assessed the extent to which such information was included on prominent health websites oriented towards the general public, and evaluated how it was explained. Design: Cross-sectional study. Setting: Websites identified through Google searches in England (United Kingdom) and New South Wales (Australia) for “breast cancer screening” and further websites included based on our prior knowledge of relevant organisations. Main outcomes: Content analysis was used to determine whether information on overdiagnosis or DCIS existed on each site, how the concepts were described, and what statistics were used to quantify overdiagnosis. Results: After exclusions, ten UK websites and eight Australian websites were considered relevant and evaluated. They originated from charities, health service providers, government agencies, and an independent health organisation. Most contained some information on overdiagnosis (and/or DCIS). Descriptive information was similar across websites. In the UK sample, statistical information was often based on estimates from the Independent UK Panel on Breast Cancer Screening; the most commonly provided statistic was the ratio of breast cancer deaths prevented to overdiagnosed cases (1:3). A range of other statistics was included, such as the yearly number of overdiagnosed cases and the proportion of women screened who would be overdiagnosed. Information on DCIS and statistical information were found less commonly on the Australian websites. Conclusions: Online information about overdiagnosis has become more widely available in 2015-16 compared with the limited accessibility indicated by older research. However, there may be scope to offer more information on DCIS and overdiagnosis statistics on Australian websites. Moreover, the variability in how estimates are presented across UK websites may be confusing for the general public

Perceptually-tuned grayscale characters based on parametrisable component fonts

Our component-based parametrisable font system is a newly developed font description and reproduction technology. It incorporates for each basic character shape a software method responsible for the synthesis of an instance of that character. A given font is synthesized by providing appropriate font parameters to these character synthesis methods. Numerous concrete fonts can be derived by simply varying the parameters. Such variations offer high flexibility for synthesizing derived fonts (variations in condensation, weight and contrast) and enable saving a considerable amount of storage space. We show that with component-based parametrisable fonts, high quality perceptually-tuned grayscale characters can be generated without requiring hinting information. Generating perceptually-tuned grayscale characters with parametrized component-based fonts consists in automatically adapting the phase of some of the character's parameters in respect to the underlying grid and in ensuring that thin character parts are strong enough not to disappear (weight-control). The presented method is especially powerful for generating high-quality characters on LCD displays (cellular phones, pen-computers, electronic books, etc..

Model-based matching and hinting of fonts

In digital computers, phototypesetters and printers, typographic fonts are mainly given by their outline descriptions. Outline descriptions alone do not provide any information about character parts like stems, serifs, shoulders, and bowls. But, in order to produce the best looking characters at a given size on a specific printer, nonlinear operations must be applied to parts of the character shape. At low-resolution, grid-fitting of character outlines is required for generating nice and regular raster characters. For this reason, grid-fitting rules called hints are added to the character description. Grid-fitting rules require as parameters certain characteristic points within the shape outlines. In order to be able to detect these characteristic points in any given input font, a topological model representing the essence of the shapes found in typographic latin typefaces is proposed. This model includes sufficient information for matching existing non-fancy outline fonts to the model description. For automatic hint generation, a table of applicable hints is added into the topological model description. After matching a given input shape to the model, hints which can be applied to the shape of the given font are taken and added to its outline description. Furthermore, a structural description of individual letter shape parts using characteristic model points can be added to the model. Such a description provides knowledge about typographic structure elements like stems, serifs and bowl

Parameterizable fonts based on shape components

We propose a new, highly flexible font description method that explicitly describes characters as assemblies of parameterizable shape components. By varying global parameters, we can derive fonts that vary in weight, condensation, and shape. Fonts made of shape components are flexible parameterizable designs, which we can easily adapt to various display and printing conditions (such as condensed font when lacking display space, high-quality optical scaling, adaptation of fonts to existing character metrics). Besides applications related to typeface design, fonts based on parameterizable components may be used in portable devices where memory is scarce. A single parameterizable design and its variations may allow enough flexibility for providing both high-quality antialiased fonts at low resolution and typefaces for high-resolution printin

Influence of diffraction on the spectrum and wavefunctions of an open system

In this paper, we demonstrate the existence and significance of diffractive orbits in an open microwave billiard, both experimentally and theoretically. Orbits that diffract off of a sharp edge of the system are found to have a strong influence on the transmission spectrum of the system, especially in the regime where there are no stable classical orbits. On resonance, the wavefunctions are influenced by both classical and diffractive orbits. Off resonance, the wavefunctions are determined by the constructive interference of multiple transient, nonperiodic orbits. Experimental, numerical, and semiclassical results are presented.Comment: 27 pages, 29 figures, and 3 tables. Submitted to Physical Review E. A copy with higher resolution figures is available at http://monsoon.harvard.edu/~hersch/papers.htm

Maximizing Neumann fundamental tones of triangles

We prove sharp isoperimetric inequalities for Neumann eigenvalues of the Laplacian on triangular domains. The first nonzero Neumann eigenvalue is shown to be maximal for the equilateral triangle among all triangles of given perimeter, and hence among all triangles of given area. Similar results are proved for the harmonic and arithmetic means of the first two nonzero eigenvalues

Light intensity modulates the regulatory network of the shade avoidance response in Arabidopsis.

Plants such as Arabidopsis thaliana respond to foliar shade and neighbors who may become competitors for light resources by elongation growth to secure access to unfiltered sunlight. Challenges faced during this shade avoidance response (SAR) are different under a light-absorbing canopy and during neighbor detection where light remains abundant. In both situations, elongation growth depends on auxin and transcription factors of the phytochrome interacting factor (PIF) class. Using a computational modeling approach to study the SAR regulatory network, we identify and experimentally validate a previously unidentified role for long hypocotyl in far red 1, a negative regulator of the PIFs. Moreover, we find that during neighbor detection, growth is promoted primarily by the production of auxin. In contrast, in true shade, the system operates with less auxin but with an increased sensitivity to the hormonal signal. Our data suggest that this latter signal is less robust, which may reflect a cost-to-robustness tradeoff, a system trait long recognized by engineers and forming the basis of information theory