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Processing of the amyloid precursor protein (APP) via the amyloidogenic pathway is associated with the etiology of Alzheimer’s disease. The cleavage of APP by β-secretase to generate the transmembrane 99-residue C-terminal fragment (C99) and subsequent processing of C99 by γ-secretase to yield amyloid-β (Aβ) peptides are essential steps in this pathway. Biochemical evidence suggests amyloidogenic processing of C99 occurs in cholesterol- and sphingolipid-enriched liquid ordered phase membrane raft domains. However, direct evidence that C99 preferentially associates with rafts has remained elusive. Here, we test this idea by quantifying the affinity of C99-GFP for raft domains in cell-derived giant plasma membrane vesicles. We find that C99 is essentially excluded from ordered domains in HeLa cells, SH-SY5Y cells and neurons, instead exhibiting a strong (roughly 90%) affinity for disordered domains. The strong association of C99 with disordered domains occurs independently of its cholesterol binding activity, homodimerization, or the familial Alzheimer disease Arctic mutation. Finally, we confirm previous studies suggesting that C99 is processed in the plasma membrane by α-secretase, in addition to the well-known γ-secretase. These findings suggest that C99 itself lacks an intrinsic affinity for raft domains, implying either that amyloidogenic processing of the protein occurs in disordered regions of the membrane, that processing involves a marginal sub-population of C99 found in rafts, or that as-yet-unidentified protein-protein interactions involving C99 in living cells drive it into rafts to promote its cleavage therein.

International audience; Given the significant land holdings of the U.S. Department of Defense, and the importance of those lands to support a variety of inherently damaging activities, application of sound natural resource conservation principles and proactive monitoring practices are necessary to manage military training lands in a sustainable manner. This study explores a method for, and the utility of, analyzing vegetation condition and trends as sustainability indicators for use by military commanders and land managers, at both the national and local levels, in identifying when and where vegetation-related environmental impacts might exist. The BFAST time series decomposition method was applied to a ten-year MODIS NDVI time series dataset for the Fort Riley military installation and Konza Prairie Biological Station (KPBS) in northeastern Kansas. Imagery selected for time-series analysis were 16-day MODIS NDVI (MOD13Q1 Collection 5) composites capable of characterizing vegetation change induced by human activities and climate variability. Three indicators related to gradual interannual or abrupt intraannual vegetation change for each pixel were calculated from the trend component resulting from the BFAST decomposition. Assessment of gradual interannual NDVI trends showed the majority of Fort Riley experienced browning between 2001 and 2010. This result is supported by validation using high spatial resolution imagery. The observed versus expected frequency of linear trends detected at Fort Riley and KPBS were significantly different and suggest a causal link between military training activities and/or land management practices. While both sites were similar with regards to overall disturbance frequency and the relative spatial extents of monotonic or interrupted trends, vegetation trajectories after disturbance were significantly different. This suggests that the type and magnitude of disturbances characteristic of each location result in distinct post-disturbance vegetation responses. Using a remotely-sensed vegetation index time series with BFAST and the indicators outlined here provides a consistent and relatively rapid assessment of military training lands with applicability outside of grassland biomes. Characterizing overall trends and disturbance responses of vegetation can promote sustainable use of military lands and assist land managers in targeting specific areas for various rehabilitation activities.

Selection of sewer pipe material for a project is traditionally based on engineering principles and cost effectiveness. This approach typically does not factor in the upstream or downstream environmental or human health aspects of the sewer pipe material. Prompted by the City of Portland’s Toxics Reduction Strategy (2006), Sustainable Procurement Policy (2008), Healthy Purchasing Initiative (2012) and related sustainability policies, the City’s Bureau of Environmental Services (BES, “Bureau”) began exploring the implications of including the environmental and human health impacts of pipe material into pipe selection decisions. In 2012 the BES contracted an independent consulting firm to review publicly available sewer pipe life cycle assessments (LCAs) to see if any conclusions could be made regarding which material (reinforced concrete, polyvinyl chloride, or vitrified clay pipe) is environmentally preferable. This paper discusses the findings of this review and how this exploration of the upstream and downstream environmental and human health impacts of sewer pipe material has fostered new discussions within BES regarding pipe material selection.

A new resonance ionization mass spectrometry system at the National Institute of Standards and Technology using glow discharge atomization and continuous-wave lasers has been developed. Low concentrations of 133Cs in a silver matrix have been measured using this new system. In addition a detailed characterization of the glow discharge source and laser ionization processes are made.

This paper reports on preliminary efforts to design and implement a novel combination of a laser, a glow discharge atom source, and a magnetic sector mass spectrometer to be used for resonance ionization of the discharge sputtered material. In this experimental design, a glow discharge source has been constructed and interfaced to a magnetic sector mass spectrometer. The laser is then focused in a spatial region between the exit orifice of the glow discharge source and the extraction optics of the mass spectrometer. Laser interaction in the low pressure region external to the discharge plasma is believed to provide several advantages for resonance ionization over previous designs in which the laser was allowed to interact within the discharge plasma. Preliminary results show resonance ionization to improve the isotopic ratios of iron in an aluminum matrix (iron-58 content of 396 μg g −1 ) relative to those observed directly from the glow discharge which are subject to isobaric overlaps.

A significant number of pupils in UK schools learn English as an additional language (EAL). Relative differences between the educational attainment of this group and monolingual, English-speaking pupils call for an exploration of the literacy needs of EAL learners.This study explores the developmental progression of reading and listening comprehension skills and a range of reading-related skills in EAL learners, whose first language is of South Asian origin, and their monolingual peers.Participants were 39 children learning EAL and 39 monolingual, English-speaking children who were all in school Year 3 at the start of the study.Children completed standardized measures of comprehension, vocabulary, reading accuracy, and reading fluency in school Year 3 and again in Year 4.The results suggest that, although children learning EAL often demonstrate fast and accurate reading accuracy skills, lower levels of vocabulary knowledge place significant constraints on EAL learners' comprehension of spoken and written texts.Reciprocal relationships between vocabulary and comprehension may lead to increasing gaps in reading comprehension between monolingual and EAL pupils over time. It is proposed that support for the development of vocabulary skills in children learning EAL is needed in early years' classrooms.

Conductivities have been measured for glasses in the AgI–Ag2O–MoO3 system at pressures from 0 to 10 kbar, and in glasses previously densified at 50 kbar. All the glasses show a progressive decrease in conductivity with increasing pressure. The activation volumes for Ag+ ion migration fall in the range 2.8–2.1 cm3 mol−1, decreasing with increasing AgI content. Similar decreases in conductivity were brought about by densification, indicating that new glasses can be prepared with properties dependent upon their pressure history.

The objective of this work was to identify sources of nonpoint source pollution resulting from military activities, to assess the impact of this pollution on surface water quality, and to provide information for commanders to lessen the impact of training on water quality. Vehicle tracks prevent sheet flow of runoff to streams. Effectiveness of native grass in reducing nonpoint pollution was assessed on hillslopes. Using LIDAR elevation data, soil, and vegetation information, a GIS tool was developed to identify likely locations of gullies. A sediment concentration sensor was developed for use in streams. Sensor data was recorded using wireless communication technology. Impact of constructed low-water fords on stream stability was assessed. Recommendations for location and design of low-water fords are provided.`

A theoretical model for the response of glass-forming systems to three-step thermal cycles is reviewed, and is shown to predict two important features. First, under limiting conditions of rapid heating of well-stabilized glasses, a single (main) peak in the heat capacity occurs at a temperature which depends strongly on the experimental variables. This dependence is a unique function of the parameter x , controlling the relative contributions of temperature and structure to the retardation times, and provides a rational means of evaluating x which is shown to be experimentally feasible. Second, when these thermal cycles involve the opposite conditions of slow heating of poorly stabilized glasses, then either two peaks (a main peak and an upper peak) or a single upper peak may be observed. The main peak and the upper peak are quite different in nature, particularly in respect of the manner in which they depend on the experimental variables, and data in the literature are used to show that all reported observations of double peaks can be explained qualitatively on the basis of this theoretical model.

The response of amorphous polymers on heating at constant rate in the differential scanning calorimeter is analysed as a function of the whole thermal history of the polymer. First, it is shown that a quantitative analysis of the data should make allowance for thermal gradients in the sample, which tend to broaden the response. Subsequently, the data are interpreted on the basis of the Tool-Narayanaswamy approach and involving three material parameters: an activation energy, Δh*; a parameter x (0

Glassy materials have been of service to mankind for centuries, from the earliest soda-lime-silicate glasses to the present sophisticated developments in, for example, metallic, fluoride and superionic glasses. Throughout this time, artefacts have been produced with a very wide range of functions: objects of exquisite beauty, such as the Venetian ‘mille fiori’ ornaments and the stained glass windows of many ancient cathedrals, high technology applications such as optical fibres for communications,‘ smart’ glass for controlled transmission, and slow-release glasses for regulating drug dosages, as well as the more commonplace requirements for containers and glazing. What is perhaps surprising about this remarkable success of glass in general is that the glassy state should still remain today so difficult to define with any precision. Even the seemingly simple question of whether a glass should be considered as a liquid or as a solid remains open to discussion.

We have examined the imaging of 0.3 μm equal line/space patterns, in 1 μm of Shipley SN248 resist (referred to as XP8843, in this paper) using projection lithography with deep‐UV exposure (248 nm). Experimentally, we have observed some interesting development effects for these small features with high aspect ratios, which highlight the role of developer agitation when using this resist. Our simulations, using a vector model to simulate the exposure, show that because of the high contrast of this resist, there is a greater depth of focus for printing 0.3 μm line space patterns when using a numerical aperture (NA) of 0.42 than 0.6. Interestingly, we see that the process window, when using a NA of 0.6 is only slightly greater when using a thin (0.3 μm) resist than when using a thick (1 μm) resist. This is due to the low absorption of the resist at 248 nm. Unfortunately the low absorption of the resist makes it extremely sensitive to thickness changes when printing on highly reflective substrates, e.g., bare silicon.

Fourier‐transform infrared (FTIR) spectrometry and dissolution rate measurements are used to compare chemical–physical mechanisms in electron beam and deep‐ultraviolet (UV) optical exposure of a chemically amplified negative crosslinking resist, Shipley XP‐8843 (SNR‐248). In contrast to optical exposure, up to 20% of the maximum extent of reaction by the melamine crosslinking agent, as measured by the change in peak‐to‐peak absorbance of the infrared (IR) spectrum at 990–1070 cm−1, was observed after electron beam exposure at nominal exposure doses of 0.5–3 μC/cm2. For both electron‐beam and optical exposure, the kinetics of the acid‐catalyzed crosslinking reactions during the postexposure bake (PEB) were similar and the saturation value of the crosslinking reaction measured by the FTIR was identical. A plot of the dissolution rate versus the degree of crosslinking for normal lithographic doses was single‐valued and tended to follow comparable data for optical exposure. When doses >5 μC/cm2 are used without a PEB, the slowing of the dissolution rate is less than expected from IR spectral change. Contrary to typical electron beam exposed negative resists, slightly underexposing small features produced a reentrant profile apparently owing to the high contrast of this resist.

The structural recovery of polystyrene glasses subjected to thermal cycles in the glass transition region is studied by differential scanning calorimetry and by dilatometry. Three different types of behaviour are observed in respect of the peak in the specific heat capacity or thermal expansion coefficient on heating, and are found to be in full agreement with the predictions of the KAHR model. First, for well-stabilized glasses, the dependence of the (main) peak temperature on heating rate and annealing time yields consistent values for the structure parameter x by means of the peak-shift method. Second, for poorly-stabilized glasses, the (upper) peak temperatures shift quite differently, but again consistently with theory. Third, for glasses intermediate between poorly-and well-stabilized conditions, both main and upper peaks can be observed simultaneously in the same endotherm.

Thermal behavior of glasses, as observed from the isobaric variations of volume, v, and enthalpy, H, is analyzed in terms of retardation kinetics. A phenomenological theory involving a single retardation time, τ, is developed, assuming that molecular mobility is controlled essentially by the actual free volume, or configurational entropy of the glassy specimen. The characteristic features of the v and H isobars, as derived from the theory, are examined as a function of the thermal history of a typical glassy specimen. The respective contributions of temperature and structural parameters to τ, are also discussed in terms of the characteristic parameters of the isobars. The theoretical predictions are compared with some dilatometric data obtained with an atactic polystyrene. The comparison reveals the limitations of the theoretical treatment and suggests that glass-transition phenomena involve more than one retardation mechanism.

SUMMARY: Heterozygous diploids were produced between a wild-type strain of Penicillium chrysogenum and two strains derived from it. The derived strains had been isolated after several and latterly divergent selection steps, selection being made at each step for higher penicillin yield. The diploids had penicillin titre values near that of the wild-type strain so that mutations for increased penicillin production which had been accumulated in the derived strains appeared in the main to be recessive. First-order segregants isolated from the heterozygous diploids were in each case predominantly of one phenotype.

SUMMARY: As a preliminary to an investigation of the inheritance of penicillin productivity in Penicillium chrysogenum several strains were genetically labelled with nutritional deficiencies and mutant spore colours. Few auxotrophs of P. chrysogenum retained the potential for penicillin yield of their parents. An analysis suggests that when loss of penicillin production occurred in an auxotroph it was most likely due to pleiotropic effects of the single mutation to auxotrophy.

Several heterozygous diploids were made between genetically labelled derivatives of two strains ofPenicillium chrysogenum which produced relatively large amounts of penicillin and were of divergent lineage. The derivatives were labelled with spore colour and nutritional mutations. The diploids, although uniform in having wild type spore colour and being prototrophic, ranged from types having penicillin yields close to that of the original parents to types having less than a quarter of this titre level. Intermediate types had titre levels of about half to threequarters that of the high yielding diploids. Segregants were selected which had arisen naturally and also after nitrogen mustard treatment; most had the spore colour and auxotrophic phenotype of one or other immediate parent. From diploids of low and intermediate titre only haploid segregants with the genetical markers of one parent could be recovered with intact penicillin yield; haploids with the genetic markers of the other showed a marked reduction in yield. However, from diploids of high yield, both parental types could be recovered showing no loss of their original penicillin yield. The bearing of these results is discussed on the suggestion that different degrees of homozygosity between diploids may account for the titre variation observed. An alternative suggestion that mutations suppressive to penicillin titre might cause such variation is also considered.

A partir de resultats en RMN de 57 Fe sur huit ferrocenes, sont determines le domaine des deplacements chimiques pour Fe lie a l'azote, l'effet des substituants sur les deplacements de 57 Fe, et les mecanismes de relaxation pour 57 Fe

The creep rate of polyethylene following an imposed temperature change is observed to exceed the rate predicted theoretically. The enhancement of creep rate is attributed to thermoelastic stresses generated by the anisotropic thermal expansion of the polymer crystals.

If the motor theory of speech perception is at least partially true, children with articulation problems should do relatively poorly in a typical verbal transformation task. Twelve children aged from 6 yrs 10 mo to 8 years 10 mo with misarticulation of /s/ were compared with 12 matched children with normal speech. Since children with articulation errors have difficulty processing time-compressed speech, the two groups were differentiated also on the basis of a speech discrimination task involving time-compressed stimuli. All Ss listened to three 1-min presentations of the nonsense word /sus/ played repeatedly with a 400-msec interstimulus interval; they pressed one of 4 buttons for each stimulus indicating perception of /sus/, /theta us/, /fus/, and "other." There were fewer transformations for the experimental group and different response profiles for the two groups, suggesting a less mature perception-production linkage in those with articulatory problems.

A partir de resultats en RMN de 57 Fe sur huit ferrocenes, sont determines le domaine des deplacements chimiques pour Fe lie a l'azote, l'effet des substituants sur les deplacements de 57 Fe, et les mecanismes de relaxation pour 57 Fe

Acoustic and perceptual correlates of velopharyngeal competency in two groups of retarded (one Down syndrome, one idiopathic) and one group of nonretarded subjects, equally divided between males and females, was evaluated. There were 20 young adults in each group. Acoustic measures of hypernasality were obtained through analysis by TONAR II. Perceptual judgments were rendered by 15 listeners. Results of perceptual and acoustic analyses revealed that those persons with Down syndrome were significantly more hypernasal than were the other two groups. Those with idiopathic retardation were more hypernasal than were nonretarded subjects.

Many problems in early vision can be formulated in terms of minimizing a cost or energy function. Examples are shape-from-shading, edge detection, motion analysis, structure from motion, and surface interpolation. (A review can be found elsewhere.(1)) Poggio and Koch(2) showed that quadratic variational problems, an important subset of early-vision tasks, can be “solved” by linear, analog electrical or chemical networks. However, in the presence of discontinuities the cost function is nonquadratic, raising the question of designing efficient algorithms for computing the optimal solution. We will show in the case of surface interpolation, a common problem in early vision, how the use of line processes leads to nonconvex energy functions and demonstrate how this problem can be solved by the use of hybrid or purely analog electrical networks, related to those proposed by Hopfield and Tank.(3) These results suggest a novel computational strategy for solving early-vision problems in both biological and real-time artificial vision systems.

Three patients with congenital hypothyroidism missed on routine screening due to normal low thyrotrophin concentrations in the neonatal period presented in later childhood. Clinicians should remain aware of hypothyroidism as a cause of morbidity in early childhood despite a national screening programme.

Three strains ofPenicillium chrysogenum selected for high penicillin yield and of independent lineage were marked with suitable genetical characters prior to the synthesis of several heterozygous diploids. These parental strains had domestic codes, C, D and Y. Two diploids, between differently labelled mutants of strain C and Y, produced similar amounts of penicillin to strain C, which was less than that produced by strain Y. Previous work had indicated that genes responsible for increased penicillin yield were recessive and the present results suggested that such genes in strains C and Y were allelic, apart from the presence of one or more additional recessive mutations leading to greater penicillin production in the higher yielding parent. Three diploids made between mutants of strains D and Y were lower in penicillin yield than either original parent and only in the case of one diploid compared with one of the parental strains was this difference not significant. In strains D and Y, therefore, there may have been some recessive genes concerned with increasing penicillin yield which were non-allelic. However, no first order segregants arising spontaneously or subsequent to X-ray treatment produced higher levels of penicillin than the better yielding original parent in any cross.

PARRY and Tabor1 have observed a significant time dependence of the dynamic shear modulus (G′) of crystalline polymers at high hydrostatic pressure (10,000 pound inch−2). The modulus observed a few seconds after the increase in pressure is lower than the modulus observed at later times. There are two obvious explanations of this effect. The first is that it is due to a time-dependent bulk compliance (B). A pressure-induced reduction in volume increases G′. If B is time dependent, then the volume will also be time dependent and will continue to decrease after the increase in pressure, thus rendering G′ time dependent. The second explanation is that the time dependence of G′ is due to the pressure-induced generation of shear stresses in the heterogeneous solid. Of these explanations Parry and Tabor1 favour the second. This view is supported by the following argument.

Previous work has indicated that the optimum calving interval for Friesian/Holstein dairy cattle is 365 days. However, a number of studies in the UK, USA and Israel have suggested that this is difficult to achieve with high yielding cows. This apparent conflict prompted ADAS to undertake a national study to investigate the link between milk production, body condition and reproductive performance in high yielding herds.