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Keyhole aqueduct syndrome is a rare progressive neurodegenerative disorder describing a unique set of neuro-ophthalmologic, neuroimaging, and histopathological findings on autopsy. A midline mesencephalic cleft communicating with the cerebral aqueduct resembling syrinx is seen on imaging and histopathology. There are 9 cases published in the literature. We encountered a patient with vertical nystagmus, internuclear ophthalmoplegia, and progressive ataxia who has a midline cleft connecting the cerebral aqueduct with the interpeduncular cistern highlighting a distinguishing feature of this syndrome. [ABSTRACT FROM AUTHOR]

Antibody drug conjugates (ADCs) are an emerging class of chemotherapeutic cancer treatment agents that combine the targeting specificity of antibodies with the efficient cell-killing potential of cytotoxic drugs. Unlike their protein and small-molecule therapeutic counterparts, the stability and degradation properties of ADCs are relatively unknown. Theoretically, ADC stability could be governed by properties and processes stemming from both the antibody and the linker-toxin chemistry. Recently, systematic studies of intrinsic ADC molecule stability have been presented in the primary literature. As there are burgeoning industrial and academic efforts aimed at developing optimized conjugation chemistries and antibody engineering approaches for next-generation ADCs, it is important to capture the current state of understanding of ADC stability. In this minireview, we discuss aspects of physical and chemical stability of ADCs gathered from a survey of the literature and illustrate how investigations into stability enable the development of more effective ADC molecules for the future. [ABSTRACT FROM AUTHOR]

Although controlling the interfacial chemistry of electrodes in Li-ion batteries (LIBs) is crucial for maintaining the reversibility, electrolyte decomposition has not been fully understood. In this study, electrolyte decomposition on model electrode surfaces (Au and Sn) was investigated by in situ attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy. Simultaneously obtained ATR-FTIR spectra and cyclic voltammetry measurements show that lithium ethylene dicarbonate and lithium propionate form on the Au electrode at 0.6 V, whereas diethyl 2,5-dioxahexane dicarboxylate and lithium propionate form on the Sn electrode surface at 1.25 V. A noncatalytic reduction path on the Au surface and a catalytic reduction path on the Sn surface are introduced to explain the surface dependence of the overpotential and product selectivity. This represents a new concept for explaining electrolyte reactions on the anode of LIBs. The present investigation shows that catalysis plays a dominant role in the electrolyte decomposition process and has important implications in electrode surface modification and electrolyte recipe selection, which are critical factors for enhancing the efficiency, durability, and reliability of LIBs. [ABSTRACT FROM AUTHOR]

Control of the interfacial chemistry of the electrodes in lithium batteries is vitally important to their safe and effective application. Water and virtually every organic solvent is thermodynamically unstable in the presence of metallic lithium. The electrode potential of a graphite electrode in a lithium-ion battery at the top of charge is at an equivalent chemical potential. In principle, the entire lithium or charged graphite electrode can be completely consumed by reaction with the solvent if the interfacial chemistry is not adventitious, i.e. does not form a reaction self-limiting passive film. A greater understanding of the reactions of the electrolyte and the nature of passivity will be essential to utilize metallic lithium or hosts like silicon that store equivalent amounts of lithium. A surface science approach, like that presented here but now out of fashion, may provide additional insight to approaches currently being used. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Ecology Letters (2010) 13: 1149–1159 In a changing environment multiple anthropogenic stressors can have novel and non-additive effects on interacting species. We investigated the interactive effects of fishing and harmful algal blooms on the predator-sea urchin-macroalgae trophic cascade. Fishing of urchin predators had indirect negative effects on macroalgae, whereas blooms of epi-benthic dinoflagellates ( Ostreopsis siamensis) were found to have strong negative effects on urchins and indirect positive effects on macroalgae. Based on these opposing effects, blooms were expected to counteract the cascading effects of fishing. However, a large bloom of Ostreopsis led to greater divergence in macroalgae abundance between reserve and fished sites, as urchins declined at reserve sites but remained stable at fished sites. This resulted from enhanced predation rates on bloom-affected urchins at reserve sites rather than direct lethal effects of Ostreopsis on urchins. We argue that interacting stressors can facilitate or attenuate trophic cascades depending on stressor intensity and complex non-lethal interactions. [ABSTRACT FROM AUTHOR]

Abstract: Blooms of benthic dinoflagellates belonging to the tropical genus Ostreopsis are an increasingly common phenomenon in temperate regions worldwide. This is reflected in the rapid upsurge of publications on Ostreopsis from temperate regions since 2000. Relatively little is known about these blooms or their effects on other organisms. An unprecedented bloom of Ostreopsis siamensis occurred on shallow reefs in northern New Zealand in 2004 providing an opportunity to examine the dynamics of an O. siamensis bloom and its effect on community structuring sea urchins (Evechinus chloroticus). The bloom occurred following a period of calm sea conditions with warmer than average water temperatures. The cover of O. siamensis was highly ephemeral and strongly related to temporal and spatial variation in wave action. Blooms were most prevalent at sites protected from prevailing swells where O. siamensis covered 30–60% of the reef with the concentrations on macroalgae reaching 1.4×106 cellsg−1 wet weight, some of the highest recorded worldwide. Surveys of the health of sea urchins in relation to the cover of O. siamensis suggested strong negative effects on this ecologically important herbivore and urchin densities declined by 56–60% at bloom sites over the study period. Further research is needed to examine the factors controlling the distribution and intensity of this new phenomenon, and into the ecological effects of such blooms on marine communities and the potential mechanisms responsible. [Copyright &y& Elsevier]

Abstract: Encapsidation of duplex DNA by bacteriophages represents an extreme case of genome condensation, reaching near-crystalline concentrations of DNA. The HK97 system is well suited to study this phenomenon in view of the detailed knowledge of its capsid structure. To characterize the interactions involved, we combined calorimetry with cryo-electron microscopy and native gel electrophoresis. We found that, as in other phages, HK97 DNA is organized in coaxially wound nested shells. When DNA-filled capsids (heads) are scanned in buffer containing 1 mM Mg2+, DNA melting and capsid denaturation both contribute to the complex thermal profile between 82 °C and 96 °C. In other conditions (absence of Mg2+ and lower ionic strength), DNA melting shifts to lower temperatures and the two events are resolved. Heads release their DNA at temperatures well below the onset of DNA melting or capsid denaturation. We suggest that, on heating, the internal pressure increases, causing the DNA to exit—probably via the portal vertex–while the capsid, although largely intact, sustains local damage that leads to an earlier onset of thermal denaturation. Heads differ structurally from empty capsids in the curvature of their protein shell, a change attributable to outwards pressure exerted by the DNA. We propose that this transition is sensed by the portal that is embedded in the capsid wall, whereupon the structure of the portal and its interactions with terminase, the packaging enzyme, are altered, thus signaling that packaging is at or approaching completion. [Copyright &y& Elsevier]

To develop the concept of user experience in HCI, McCarthy et al. introduce the notion of enchantment in interaction design. They describe five sensibilities that support exploration and evaluation in design for enchantment. In this paper, we discuss design for enchantment in light of our approach to design for interaction, called design for meaningful mediation. Based on our experiences from case studies, we argue that ‘considering the whole person with feelings, desires and anxieties’, one of the sensibilities McCarthy et al. formulate, influences the desirability and realisation of the other four sensibilities. By way of case studies, we show how we explored the link between ‘the whole person’ and desired interaction experience in a designerly way. We place enchantment in a context of other interaction experiences and demonstrate possible design techniques relevant to design for interaction experiences, including enchantment. [ABSTRACT FROM AUTHOR]

The article reports on results of a study of the role of repeated biopsy of the prostate in predicting disease progression in patients with prostate cancer on active surveillance. A description of the experimental set-up and measurement method is provided. The study concludes that negative re-biopsy in patients with prostate cancer on active surveillance is associated with low-volume disease.

According to the vision of Ambient Intelligence, technology will seamlessly merge into people’s everyday activities and environments. A challenge facing designers of such systems is to create interfaces that fit in people’s everyday contexts and incorporate the values of daily life. This paper focuses on tangible expressive interaction as one possible approach towards linking everyday experiences to intuitive forms of interaction and presents a number of principles for expressive interaction design in this field. A case study of a tangible expressive interface to control a living room atmosphere projection system (orchestrating living room lighting, audio and video-art) is presented to illustrate and reflect upon the design principles. Furthermore, the case study describes possible techniques towards integrating the design principles into a design method. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the thermodynamic basis of HK97 assembly by scanning calorimetry and cryo-electron microscopy. This pathway involves self-assembly of hexamers and pentamers of the precursor capsid protein gp5 into procapsids; proteolysis of their N-terminal Δ-domains; expansion, a major conformational change; and covalent crosslinking. The thermal denaturation parameters convey the changes in stability at successive steps in assembly, and afford estimates of the corresponding changes in free energy. The procapsid represents a kinetically accessible local minimum of free energy. In maturation, it progresses to lower minima in a cascade punctuated by irreversible processes (“locks”), i.e. proteolysis and crosslinking, that lower kinetic barriers and prevent regression. We infer that Δ-domains not only guide assembly but also restrain the procapsid from premature expansion; their removal by proteolysis is conducive to initiating expansion and to its proceeding to completion. We also analyzed the mutant E219K, whose capsomers reassemble in vitro into procapsids with vacant vertices called “whiffleballs”. E219K assemblies all have markedly reduced stability compared to wild-type gp5 (ΔT p ∼−7 °C to −10 °C; where T p is the denaturation temperature). As the mutated residue is buried in the core of gp5, we attribute the observed reduction in stability to steric and electrostatic perturbations of the packing of side-chains in the subunit interior. To explain the whiffleball phenotype, we suggest that these effects propagate to the capsomer periphery in such a way as to differentially affect the stability or solubility of dissociated pentamers, leaving only hexamers to reassemble. [Copyright &y& Elsevier]

In HK97 capsid maturation, structural change (‘expansion’) is accompanied by formation of covalent crosslinks, connecting residue K169 in the‘E-loop’of each subunit with N356 on another subunit. We show by complementation experiments with the K169Y mutant, which cannot crosslink, that crosslinking is an essential function. The precursor Prohead-II passes through three expansion intermediate (EI) states en route to the end state, Head-II. We investigated the effects of expansion and crosslinking on stability by differential scanning calorimetry of wild-type and K169Y capsids. After expansion, the denaturation temperature (Tp) of K169Y capsids is slightly reduced, indicating that their thermal stability is not enhanced, but crosslinking effects a major stabilization (?Tp,+11°C). EI-II is the earliest capsid to form crosslinks. Cryo-electron microscopy shows that for both wild-type and K169Y EI-II, most E-loops are in the‘up’position, 30Åfrom the nearest N356: thus, crosslinking in EI-II represents capture of mobile E-loops in‘down’positions. At pH 4, most K169Y capsids remain as EI-II, whereas wild-type capsids proceed to EI-III, suggesting that crosslink formation drives maturation by a Brownian ratchet mechanism. [ABSTRACT FROM AUTHOR]

This paper assumes that there is something in the logic of the capitalist mode of production such that, in the words of Marx and Engels' Communist Manifesto, it "must nestle everywhere, settle everywhere, establish connections everywhere," giving a "cosmopolitan character to production and consumption in every country." It assumes, that is, that there is an inherent tendency in capitalism to seek to globalize. Further, it is argued that one can plausibly claim that the capitalist mode of production has succeeded, or is succeeding, in globalizing against the countervailing forces of the managing state and organized labor. It is argued that this development represents, to use Marcuse's words, something like a "closing of the universe of discourse" or a "paralysis of criticism" and the emergence of a "society without opposition," but in a context, in crucial respects, fundamentally different from that analysed by Marcuse in the 1960s. [ABSTRACT FROM AUTHOR]

According to the “amyloid backbone” model of Ure2p prionogenesis, the N-terminal domain of Ure2p polymerizes to form an amyloid filament backbone surrounded by the C-terminal domains. The latter domains retain their native glutathione-S-transferase (GST)-like fold but are sterically inactivated from their regulatory role in nitrogen catabolism. We have tested this model by differential scanning calorimetry of soluble and filamentous Ure2p and of soluble C-terminal domains, combined with electron microscopy. As predicted, the C-terminal domains respond to thermal perturbation identically in all three states, exhibiting a single endotherm at 76 °C. In contrast, no thermal signal was associated with the N-terminal domains: in the soluble state of Ure2p, because they are unfolded; in the filamentous state, because their robust amyloid conformation resists heating to 100 °C. [Copyright &y& Elsevier]

A primer extension assay is used to perform highly multiplexed genotyping of single nucleotide polymorphisms (SNPs) present in genomic DNA amplified by a multiplex PCR. The assay uses matrix-assisted laser desorption ionization time-of-flight mass spectrometry to accurately measure the masses of short oligonucleotide primers extended by a single dideoxynucleotide. The multiplexed genotyping assays rely on the natural molecular weight differences of DNA bases. By careful analysis of primer composition complementary to the target, or by judicious addition of one or more noncomplementary 5′ bases to the genotyping primers, mass spectra of interleaved genotyping products can be generated with no ambiguity in allele assignment. Using a model multiplex PCR system, we demonstrate the ability to perform 12-fold multiplex SNP analysis. [ABSTRACT FROM AUTHOR]

Discusses the impact of vertebral fractures and predictors of physical impairment and health care utilization. Data collection from postmenopausal Japanese American women; Identification of vertebral fractures through serial spine radiographs; Association between poor physical function and increase in vertebral fractures; Emphasis on identification of risk factors.

Examines the existing literature on osteoporosis. Definition of osteoporosis; Relationship between age and the prevalence and incidence of osteoporosis; Association between mortality with osteoporosis and hip fractures; Consequences of osteoporotic fractures; Risk factors for osteoporotic fractures.

Presents high-pressure mass spectrometric experiments to probe details of double minimum potential energy surface for gas-phase SN2 reactions. Determination of the well depths and entropy changes of methyl, ethyl, isopropyl, and tert-butyl chlorides and bromides from temperature dependence of equilibrium constants for adduct formation.

Presents an analysis of deoxyribonucleic acid (DNA) fragments from conventional and microfabricated polymerase chain reaction (PCR) devices using delayed extraction MALDI-TOF mass spectrometry. Details on applications of PCR devices; Challenges of PCR product analysis by mass spectrometry; Results and discussion on the findings.

Presents an approach to single-nucleotide polymorphism discrimination to PCR-amplified DNA (deoxyribonucleic acid). What this approach is based on; Application of the assay to polymorphisms in hypervariable region 1 of the human mitochondrial genome and gene; Results obtained from experiments conducted.

Analyses an important class of human genetic polymorphisms, short tandem repeats (STRs), with the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS. Purpose of the evaluation; Indications of the evaluation.

Presents information on a study which examined clinical consequences associated with vertebral fractures. Why persons with vertebral fractures experience more pain than that suffered from other types of fractures; Criteria for the assessment of vertebral fractures; Details on the physical and functional recovery of persons with vertebral fractures; Information on the results of studies conducted.

Examines the use of radiographic absorptiometry (RA) of bones in the diagnosis of osteoporosis. Integration of computerized image processing to radiography for improved accuracy; Applicability of RA techniques in a clinical setting; Cost effectiveness of RA.

Objective: To determine the independent contributions of bone mass and existing fractures as predictors of the risk for new vertebral fractures.Subjects: Postmenopausal Japanese-American women.Measurements: Baseline measurements of the distal radius, the proximal radius, and the calcaneus were obtained in 1981 using single-photon absorptiometry. Measurements of the lumbar spine were obtained in 1984 using dual-photon absorptiometry. Prevalent vertebral fractures were identified using dimensions measured on lateral radiographs; vertebral height values more than 3 SD below vertebra-specific means were considered to indicate fracture. Statistical models were used to evaluate the utility of bone mass and existing (prevalent) fractures to predict the risk for new fractures during an average follow-up of 4.7 years.Main Results: Differences of 2 SD in bone mass were associated with fourfold to sixfold increases in the risk for new vertebral fractures. A single fracture at the baseline examination increased the risk for new vertebral fractures fivefold. Presence of two or more fractures at baseline increased the risk 12-fold. A combination of low bone mass (below the 33d percentile) and the presence of two or more prevalent fractures increased the risk 75-fold, relative to women with the highest bone mass (above the 67th percentile) and no prevalent fractures. Stature, body mass index, arm span, and spinal conditions such as scoliosis, osteoarthritis, and sacroiliitis did not predict fracture incidence (P greater than 0.05). Weight was marginally predictive (P = 0.04) of fracture incidence but became nonpredictive after adjusting for bone mass (P greater than or equal to 0.05).Conclusions: Both bone mass and prevalent vertebral fractures are powerful predictors of the risk for new vertebral fractures. Combining information about bone mass and prevalent fracture appears to be better for predicting new fractures than either variable alone. Physicians can use these risk factors to identify patients at greatest risk for new fractures. [ABSTRACT FROM AUTHOR]