bluuebunny/crossref_metadata_2025 huggingface dataset:
LSD1/CoREST is an allosteric nanoscale clamp regulated by H3-histone-tail molecular recognition
Authors: Baron Riccardo , Vellore Nadeem A.
Published: July 2012

The complex of lysine-specific demethylase-1 (LSD1/KDM1A) with its corepressor protein CoREST is an exceptionally relevant target for epigenetic drugs. Here, we provide insight into the local and global changes of LSD1/CoREST conformational dynamics that occur upon H3 binding on the basis of a total cumulative time of one microsecond molecular dynamics simulation. The LSD1/CoREST complex functions as an allosteric nanoscale-binding clamp, which is regulated by substrate binding. In the unbound state, LSD1/CoREST reversibly visits clamp states that are more open or significantly more closed compared with the available X-ray crystal structures. The Lys triad of residues Lys355, Lys357, and Lys359 gates the entrance of the H3 pocket. H3 binding shifts the pocket breathing dynamics toward open, higher-volume states while reducing the overall flexibility of the LSD1/CoREST nanoscale clamp. We show that the H3 pocket is an allosteric site for the regulation of the rotation of the amino oxidase domain with respect to the Tower domain. The allosteric mechanism relies on the specific reduction of nanoscale domain rotation upon local H3-tail binding. Instead, clamp opening/closing motions that do not involve domain rotation only reduce in amplitude yet are dominant in the bound state. Overall, our data suggest that the H3 binding pocket is a central target site to (
i
) switch off LSD1 amino oxidase activity, thus H3-tail demethylation; (
ii
) block the competitive binding of transcription factors; and (
iii
) prevent chromatin anchoring to LSD1/CoREST. This study underscores the importance of receptor flexibility for future epigenetic drug discovery.
Quantitative profiling of caspase-cleaved substrates reveals different drug-induced and cell-type patterns in apoptosis
Authors: Shimbo Kazutaka , Hsu Gerald W. , Nguyen Huy , Mahrus Sami , Trinidad Jonathan C. , Burlingame Alma L. , Wells James A.
Published: July 2012

Proapoptotic drugs are a mainstay of cancer drug treatment. These drugs stress cells and ultimately trigger the activation of caspases, cysteine-class proteases that cleave after aspartic acid and deconstruct the cell. It is well known that cells respond differently to proapoptotic cancer drug treatments. Here, using a global and unbiased quantitative N-terminomics technology, we show that ∼500 products of caspase cleavage and their kinetics vary dramatically between cell type and cytotoxic drug treatment. It is likely that variations arise from differences in baseline proteome composition of the cell type and the alterations induced by drug treatments to yield a unique cohort of proteins that caspases finally target. Many targets are specific to both drug treatment and cell type, providing candidate-specific biomarkers for apoptosis. For example, in multiple myeloma cells treated with the proteasome inhibitor bortezomib, levels of activating transcription factor-4 increase dramatically early in drug treatment and then decrease upon cleavage by activated caspases. Thus, caspase-derived cleavage products are a sensitive reflection of cell-type and drug-induced stress, and provide useful fingerprints for mechanisms of drug action and response.
Pathway-specific control of reward learning and its flexibility via selective dopamine receptors in the nucleus accumbens
Authors: Yawata Satoshi , Yamaguchi Takashi , Danjo Teruko , Hikida Takatoshi , Nakanishi Shigetada
Published: July 2012

In the basal ganglia, inputs from the nucleus accumbens (NAc) are transmitted through both direct and indirect pathways and control reward-based learning. In the NAc, dopamine (DA) serves as a key neurotransmitter, modulating these two parallel pathways. This study explored how reward learning and its flexibility are controlled in a pathway-specific and DA receptor-dependent manner. We used two techniques (
i
) reversible neurotransmission blocking (RNB), in which transmission of the direct (
d
-RNB) or the indirect pathway (I-RNB) in the NAc on both sides of the hemispheres was selectively blocked by transmission-blocking tetanus toxin; and (
ii
) asymmetric RNB, in which transmission of the direct (
d
-aRNB) or the indirect pathway (I-aRNB) was unilaterally blocked by RNB techniques and the intact side of the NAc was infused with DA agonists or antagonists. Reward-based learning was assessed by measuring goal-directed learning ability based on visual cue tasks (VCTs) or response-direction tasks (RDTs). Learning flexibility was then tested by switching from a previously learned VCT to a new VCT or RDT.
d
-RNB mice and D1 receptor antagonist-treated
d
-aRNB mice showed severe impairments in learning acquisition but normal flexibility to switch from a previously learned strategy. In contrast, I-RNB mice and D2 receptor agonist-treated I-aRNB mice showed normal learning acquisition but severe impairments not only in the flexibility to the learning switch but also in the subsequent acquisition of learning a new strategy. D1 and D2 receptors thus play distinct but cooperative roles in reward learning and its flexibility in a pathway-specific manner.
Characterization of Oocyte Development in Hatchery-Reared Burbot
Authors: Foltz John R , Jensen Nathan R , Polinski Mark P , Ireland Susan C , Cain Kenneth D
Published: July 2012

Burbot Lota lota are an emerging aquaculture species. To aid in predicting the natural and hormonal-manipulated timing of ovulation and for ensuring maximum viability of eggs at spawning, this study describes oocyte maturation of hatchery-reared burbot from vitellogenesis through ovulation. At a temperature of 4°C, visual polarization of the oil globule occurred 7–13 d preovulation. The lack of uniformity in individual oocyte development was observed and persisted until approximately 2 d before ovulation, at which point complete polarization was observed in all oocytes and a condensed blastomere was observed along the inner chorion. These preliminary observations imply that implantation of gonatotropin-releasing hormone (GnRH) decreased the final maturation stage of oocyte development by 2–4 d and may aid in initiating the maturation process, the induction of which appeared to be a threshold for either a female's progression to ovulation or nonovulation and atresia. Although additional investigation may be needed to fully maximize egg fertilization success and optimize timing related to intensive spawning practices, this study lays a foundation for further investigations and provides a reference for assessing oocyte development and predicting ovulation for this species.
Defining Essential Fish Habitat for Atka Mackerel with Respect to Feeding within and Adjacent to Aleutian Islands Trawl Exclusion Zones
Authors: Rand Kimberly M. , Lowe Sandra A.
Published: July 2012

The distribution patterns of Atka mackerel Pleurogrammus monopterygius were examined, both seasonally and spatially, to identify essential feeding habitat and to add to existing knowledge of diet composition. The study focused on two local aggregations in the Aleutian Islands, Alaska: one at Seguam Pass and one near Amchitka Island. At each locale, we examined the mean stomach fullness (i.e., feeding intensity) and diet composition of randomly selected fish within and outside of trawl exclusion zones (TEZs). The trawl exclusion zones extend out 10–20 nm from Steller sea lion Eumetopias jubatus rookeries and haulouts; no trawling is allowed inside these zones. During four of the six periods examined, mean stomach fullness was higher inside the TEZ than outside it. At Seguam Pass, fish were distributed into northern and southern aggregations and diet composition varied by age, season, and location relative to the TEZs. Feeding intensity appeared to be greatest inside the TEZ in the northern portion of Seguam Pass near a productive frontal region characterized by a transition zone of well-mixed (upwelling) and stratified water. At Seguam Pass, piscivory occurred almost entirely inside the TEZ in June. Near Amchitka Island, feeding intensity was significantly higher inside the TEZ, which coincided with an increase in egg cannibalism in October. Based on these observations, we suggest that the areas of increased feeding activity in conjunction with diet composition at Seguam Pass and Amchitka Island represent essential feeding habitat for Atka mackerel.
Impacts of Interannual Environmental Forcing and Climate Change on the Distribution of Atlantic Mackerel on the U.S. Northeast Continental Shelf
Authors: Overholtz W. J. , Hare J. A. , Keith C. M.
Published: July 2012

The Northwest Atlantic stock of Atlantic mackerel Scomber scombrus is distributed from Cape Hatteras to Newfoundland and migrates great distances on a seasonal basis. Atlantic mackerel are sensitive to changes in temperature, preferring water greater than 5°C. Annual changes in the winter and early-spring distributions of Atlantic mackerel were investigated using satellite imagery, research trawl surveys, geographical information systems, and spatial and standard statistical analyses. During the past 40-plus years (1968–2008), the distribution of the stock has shifted about 250 km to the north and east. Also, a change has occurred in the depth distribution of the stock, from deeper off-shelf locations to shallower on-shelf ones. Areal and bathymetric changes in distribution are correlated with interannual temperature variability and gradual warming. These results have implications for U.S. commercial and recreational mackerel fisheries because, despite the current high abundance of the stock, the changes in distribution will probably make it more difficult to find and catch Atlantic mackerel in certain areas in the future.
Suitability of Insulin-Like Growth Factor 1 (IGF1) as a Measure of Relative Growth Rates in Lingcod
Authors: Andrews Kelly S. , Beckman Brian R. , Beaudreau Anne H. , Larsen Donald A. , Williams Greg D. , Levin Phillip S.
Published: July 2012

The effectiveness of spatial management strategies is typically evaluated through traditional biological measurements of size, density, biomass, and the diversity of species inside and outside management boundaries. However, there have been relatively few attempts to evaluate the processes underlying these biological patterns. In this study, we take the first step toward developing a relative index of body growth for lingcod Ophiodon elongatus using plasma insulin-like growth factor 1 (IGF1) with the ultimate goal of measuring spatial differences in relative growth rates. Insulin-like growth factor 1 is one of the principal hormones that stimulates growth at the cellular level in all vertebrates and shows significant relationships with body growth in many fishes. In the laboratory, we found that the level of IGF1 was related to the instantaneous growth of juvenile lingcod. In the field, we measured size, condition, and plasma IGF1 level in 149 lingcod from eight locations inside and outside marine protected areas in the San Juan Islands, Washington. The IGF1 levels in wild lingcod were highly variable from site to site for both genders, and we were able to detect differences in IGF1 across space in males. Multivariate analyses showed that the spatial patterns of IGF1 differed from those of traditional biological measurements. More work is needed to validate the relationship between IGF1 and growth in larger individuals, but our research shows the potential for IGF1 to be used as an ecological indicator.
Age, Growth, and Reproduction of Sheepsheads in South Carolina
Authors: McDonough C. J. , Wenner C. A. , Roumillat W. A.
Published: July 2012

The sheepshead Archosargus probatocephalus is a common estuarine and reef species that is found year round in South Carolina. Although not commercially important, the sheepshead is a significant recreational species, and most of the fishing pressure occurs in state waters. From 1990 to 2005, 5,692 sheepsheads were collected from fishery-dependent and fishery-independent monitoring programs in South Carolina. Fish ranged from 102 to 605 mm in fork length (FL) and were caught during every month of the year. Ages ranged from 0 to 19 years for males and from 0 to 23 years for females; the dominant age-classes were ages 2–5. Marginal increment analysis confirmed the formation of a single annulus per year, and annulus formation began in May. Males and females did not significantly differ in FL at age t(FLt) or total weight at age t (Wt); the pooled von Bertalanffy growth models were FLt = 498[1 − e−0.297(t + 1.10)] and Wt = 3,778[1 − e−0.165(t − 0.548)]2.997. Both males and females exhibited the first signs of sexual maturity at age 1, and 100% maturity was reached at age 4. Batch fecundity estimated late in the spawning season ranged from 18,400 to 738,500 oocytes/spawning event and averaged 235,000 oocytes/spawning event. Fork length, W, and age were positively correlated with fecundity. Although size was a better predictor of fecundity than age, the relationship was weak due to the high variability in size at age. Comparisons of growth parameters for sheepsheads studied in the southeastern United States indicated that South Carolina sheepsheads tend to have a larger maximum FL and a greater maximum age than fish found in the Gulf of Mexico.

Received May 24, 2010; accepted July 26, 2011
Magnetic and electrical properties of ε-Fe3N on c-plane GaN
Authors: Fang Henan , Zhang Rong , Liu Bin , Tao Zhikuo , Wang Xuefeng , Xie Zili , Xiu Xiangqian , Zheng Youdou
Published: July 2012

ε-Fe3N films on c-plane GaN are fabricated through nitridation of amorphous Fe films. From x-ray diffraction, the structures of these ε-Fe3N films are found to consist of two crystal orientations of ε-Fe3N, i.e. (0 0 2) and (1 1 1). The binding energies of Fe ions in the samples are analysed by x-ray photoelectron spectroscopy, both Fe–N and Fe–O–N peaks are observed. Scanning electron microscopy shows that the surface morphology of the ε-Fe3N films is island-like. In particular, these films are ferromagnetic at room temperature, with a coercivity of about 200 Oe according to the measured magnetic hysteresis loop. The ferromagnetism is further studied by ferromagnetic resonance spectra. With increasing angle between the incident field and the sample plane, the resonance magnetic fields of Fe and ε-Fe3N films exhibit different behaviours; the difference can be interpreted by Kittel's theory. In addition, the I–V curves and Hall measurement indicate that the ε-Fe3N films are good conductors at room temperature. On the whole, these magnetic and electrical properties demonstrate that the ε-Fe3N films are appropriate for GaN-based spintronic devices.
The Strange Surprising Adventures of Reading Balzac's
Louis Lambert
Authors: Acquisto Joseph
Published: July 2012

This article reads Balzac's
Louis Lambert
in the light of the history of rewritings of the Robinson Crusoe legend. Balzac participates in that history as one of the first figures of transition between early nineteenth-century popular rewritings of the Crusoe story for children and the many serious Crusoe-based novels for adults composed in the twentieth century. In
Louis Lambert
he makes subtle use of the Crusoe story, naming it only twice. Nevertheless, Balzac borrows and adapts structural patterns from Defoe's novel, eschewing literal travel adventure in favour of a philosophical focus. At the time when popular reworkings of Robinson Crusoe for children were at their height, Balzac paves the way for later novelists who will de-emphasize the story's moralistic aspect and inscribe it into a different set of aesthetic and philosophical concerns. Balzac and those who follow him foreground a philosophical escapade, solitary by nature, thus redrawing the map of self and world.
Gendered Constructions of the Nightmare in French Nineteenth-Century Medical Writing and Fantastic Fiction
Authors: Downing Lisa
Published: July 2012

This article considers the history of the nightmare and argues that the nineteenth century in France sees a particular efflorescence of discursive attempts, across medical and literary fields, to explain, classify, and describe experientially this phenomenological concept. The article begins with a brief pan-European prehistory of the modern notion of the ‘cauchemar’ that explores its demonological and medical origins and the sexual connotations presumed to underlie it. Then, theories and representations of the nightmare in nineteenth-century French alienism and the literary genre of the
conte fantastique
(1820–40) are examined. It is argued that specific nineteenth-century preoccupations with rationality, and the subject's potential for alienation from it, which are heavily bound up with gendered discourses and values, make the nightmare (as an exemplary experience of loss of control) a topic of fascination for physicians, writers, and thinkers. I examine the extent to which the loss of mastery experienced in the nightmare, perceived with anxiety in medical writings, becomes, in
contes fantastiques
, especially those by Théophile Gautier, a transgressive experiment with the erotic experience of liberation from expectations of socially and sexually agentic masculinity. In this way the article offers both an original interpretation of the genre of the French fantastic, and a brief cultural genealogy of a phenomenon that has a long history in demonology and medicine, drawing particular attention to its specifically French nineteenth-century dimensions.
‘En dehors de la fête’: entre présence et absence, pour une approche dialogique de l'identité dans
Les Années
d'Annie Ernaux
Authors: Hugueny-Léger Elise
Published: July 2012

Le postulat de cet article est que la conception de l'identité telle qu'elle est développée dans
Les Années
d'Annie Ernaux (2008) fonctionne sur un mouvement paradoxal de présence et absence du sujet (auteure, narratrice et personnage) ernalien. Ce mouvement, qui se réfère à une manière d'aborder à la fois le quotidien et l'écriture, et qui a été décrit par Ernaux comme la sensation d'être ‘hors de la fête’, peut se comprendre comme partie intégrante de son œuvre. Il trouve sa représentation la plus probante dans le motif même de la fête, occasion de faire mettre en jeu des interactions entre soi et autrui ainsi que des structures à la fois privées et institutionnalisées. En prenant ce motif comme point de départ, cet article propose une lecture d'Ernaux à travers les théories de Bakhtine sur le carnaval, la polyphonie et l'identité qui permettent de mettre en valeur le passage de la présence à l'absence, de soi aux autres, et le rôle de la parole d'autrui dans la constitution des
Années
. Il s'agit de comprendre comment ce texte peut être décrit comme un véritable ‘roman total’ dans le sens où il fait place à l'intertextualité, au dialogisme, où il met en lumière diverses structures sociales et laisse entrevoir une identité personnelle et narrative basée sur la question de l'altérité.
‘Comme des brebis au milieu des loups’: Biblical Ideas and Imagery in the Sermons and Pastoral Letters of the French Clergy, 1790–91
Authors: Thurston Benjamin
Published: July 2012

This article examines the role of biblical ideas and imagery in the ecclesiastical debates of 1790–91, primarily in the sermons and pastoral letters of the French bishops. These sermons and letters were among the most important means of mass communication at the end of the eighteenth century: they translated often complex ideas into a language that was accessible to millions of Frenchmen and women. The clergy of both the
Ancien Régime
and the new constitutional Church drew regularly on scriptural narratives in their doctrinal quarrels and personal feuds. These politico-theological polemics involved appeals to apostolic authority, exegeses of well-known parables, denunciations of idolatry from the Old Testament, and prophecies of Armageddon. This language reinforced antagonisms between the refractory and the constitutional clergy and contributed to the schism in the French Church.
Paired-end sequencing of Fosmid libraries by Illumina
Authors: Williams Louise J.S. , Tabbaa Diana G. , Li Na , Berlin Aaron M. , Shea Terrance P. , MacCallum Iain , Lawrence Michael S. , Drier Yotam , Getz Gad , Young Sarah K. , Jaffe David B. , Nusbaum Chad , Gnirke Andreas
Published: July 2012

Eliminating the bacterial cloning step has been a major factor in the vastly improved efficiency of massively parallel sequencing approaches. However, this also has made it a technical challenge to produce the modern equivalent of the Fosmid- or BAC-end sequences that were crucial for assembling and analyzing complex genomes during the Sanger-based sequencing era. To close this technology gap, we developed Fosill, a method for converting Fosmids to Illumina-compatible jumping libraries. We constructed Fosmid libraries in vectors with Illumina primer sequences and specific nicking sites flanking the cloning site. Our family of pFosill vectors allows multiplex Fosmid cloning of end-tagged genomic fragments without physical size selection and is compatible with standard and multiplex paired-end Illumina sequencing. To excise the bulk of each cloned insert, we introduced two nicks in the vector, translated them into the inserts, and cleaved them. Recircularization of the vector via coligation of insert termini followed by inverse PCR generates a jumping library for paired-end sequencing with 101-base reads. The yield of unique Fosmid-sized jumps is sufficiently high, and the background of short, incorrectly spaced and chimeric artifacts sufficiently low, to enable applications such as mapping of structural variation and scaffolding of de novo assemblies. We demonstrate the power of Fosill to map genome rearrangements in a cancer cell line and identified three fusion genes that were corroborated by RNA-seq data. Our Fosill-powered assembly of the mouse genome has an N50 scaffold length of 17.0 Mb, rivaling the connectivity (16.9 Mb) of the Sanger-sequencing based draft assembly.
Structure determination of L-arabinitol by powder X-ray diffraction
Authors: Derollez Patrick , Guinet Yannick , Affouard Frédéric , Danède Florence , Carpentier Laurent , Hédoux Alain
Published: July 2012

Powder X-ray diffraction patterns of the commercial phase of L-arabinitol were recorded with a laboratory diffractometer. The starting structural model was found by a Monte-Carlo simulated annealing method. The final structure was obtained through Rietveld refinements with soft restraints on the interatomic bond lengths and bond angles. H atoms of hydroxyl groups were localized by minimization of the crystalline energy. The cell is triclinic with the space group P1 and contains two molecules. The crystalline cohesion is achieved by an important network of O—H...O hydrogen bonds.
Cocrystals of 5-fluorocytosine. II. Coformers with variable hydrogen-bonding sites
Authors: Tutughamiarso Maya , Egert Ernst
Published: July 2012

Two flexible molecules, biuret and 6-acetamidouracil, were cocrystallized with 5-fluorocytosine to study their conformational preferences. In the cocrystal with 5-fluorocytosine (I), biuret exhibits the same conformation as in its hydrate. In contrast, 6-acetamidouracil can adopt two main conformations depending on its crystal environment: in crystal (II) the trans form characterized by an intramolecular hydrogen bond is observed, while in the cocrystal with 5-fluorocytosine (III), the complementary binding induces the cis form. Three cocrystals of 6-methylisocytosine demonstrate that complementary binding enables the crystallization of a specific tautomer. In the cocrystals with 5-fluorocytosine, (IVa) and (IVb), only the 3H tautomer of 6-methylisocytosine is present, whereas in the cocrystal with 6-aminoisocytosine, (V), the 1H tautomeric form is adopted. The complexes observed in the cocrystals are stabilized by three hydrogen bonds similar to those constituting the Watson–Crick C·G base pair.
Reproduction and dispersal in an ant‐associated root aphid community
Authors: IVENS A. B. F. , KRONAUER D. J. C. , PEN I. , WEISSING F. J. , BOOMSMA J. J.
Published: July 2012

Clonal organisms with occasional sex are important for our general understanding of the costs and benefits that maintain sexual reproduction. Cyclically parthenogenetic aphids are highly variable in their frequency of sexual reproduction. However, studies have mostly focused on free‐living aphids above ground, whereas dispersal constraints and dependence on ant‐tending may differentially affect the costs and benefits of sex in subterranean aphids. Here, we studied reproductive mode and dispersal in a community of root aphids that are obligately associated with the ant Lasius flavus. We assessed the genetic population structure of four species (Geoica utricularia, Tetraneura ulmi, Forda marginata and Forda formicaria) in a Dutch population and found that all species reproduce predominantly if not exclusively asexually, so that populations consist of multiple clonal lineages. We show that population viscosity is high and winged aphids rare, consistent with infrequent horizontal transmission between ant host colonies. The absence of the primary host shrub (Pistacia) may explain the absence of sex in three of the studied species, but elm trees (Ulmus) that are primary hosts of the fourth species (T. ulmi) occurred within a few km of the study population. We discuss the extent to which obligate ant‐tending and absence of primary hosts may have affected selection for permanent parthenogenesis, and we highlight the need for further study of these aphids in Southern Europe where primary hosts may occur close to L. flavus populations, so that all four root aphid species would have realistic opportunities for completing their sexual life cycle.
Th17/Treg imbalance in patients with liver cystic echinococcosis
Authors: TUXUN T. , WANG J.‐H. , LIN R.‐Y. , SHAN J.‐Y. , TAI Q.‐W. , LI T. , ZHANG J.‐H. , ZHAO J.‐M. , WEN H.
Published: July 2012

Echinococcosis is a chronic parasitic infectious disease regulated by T‐cell subsets. CD4+ CD25+ FoxP3 +  regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets and have the opposite effect on inflammation. Th17/Treg balance controls inflammation and may play an important role in the pathogenesis of immune evasion. To assess whether this balance was broken, we detected Th17/Treg functions in different levels including cell frequencies, related cytokines secretion and key transcription factors in patients with cystic echincoccosis and healthy controls. The results demonstrated that patients with cystic echinococcosis revealed significant increase in peripheral Treg number, related cytokines (IL‐10 and TGF‐β1) and transcription factor (Foxp3) levels and moderate decrease in Th17 number, related cytokines (IL‐17 and IL‐23) and transcription factor (RORγt) levels as compared with controls. Results indicated that Th17/Treg functional imbalance exists in patients with chronic cystic echinococcosis, suggesting a potential role for Th17/Treg imbalance in the pathogenesis of immune evasion in echinococcosis.
Optical coherence tomography for the evaluation of retinal and optic nerve morphology in animal subjects: practical considerations
Authors: McLellan Gillian J. , Rasmussen Carol A.
Published: July 2012

Optical coherence tomography (OCT) is a noninvasive, noncontact imaging technique capable of producing high‐resolution images of the retina and optic nerve. These images provide information that is useful for following the progression and/or resolution of posterior segment disease. Rapid advances in OCT technology allow the acquisition of increasingly detailed images, approaching the original goal of providing in vivo histopathology. Increases in scan acquisition speeds and axial resolution enhance the clinical diagnostic value of this modality. Adapting instrumentation designed for use in human patients for use in animals can be challenging. Each species has a unique set of adjustments that need to be made but it is possible to obtain reproducible, high‐quality OCT images in a variety of animals, including rodents, dogs, cats, pigs, and monkeys. Deriving quantitative measurements from OCT instruments is hindered by software algorithm errors in detecting the edges of the distinct retinal layers. These segmentation errors occur in scans of human eyes as well in other species and arise with similar frequency with each of the different OCT instruments. Manual segmentation methods to derive optic nerve head and other structural indices have been developed for several species.
A neurophysiological deficit in early visual processing in schizophrenia patients with auditory hallucinations
Authors: Kayser Jürgen , Tenke Craig E. , Kroppmann Christopher J. , Alschuler Daniel M. , Fekri Shiva , Gil Roberto , Jarskog L. Fredrik , Harkavy‐Friedman Jill M. , Bruder Gerard E.
Published: July 2012

Existing 67‐channel event‐related potentials, obtained during recognition and working memory paradigms with words or faces, were used to examine early visual processing in schizophrenia patients prone to auditory hallucinations (AH, n = 26) or not (NH, n = 49) and healthy controls (HC, n = 46). Current source density (CSD) transforms revealed distinct, strongly left‐ (words) or right‐lateralized (faces; N170) inferior‐temporal N1 sinks (150 ms) in each group. N1 was quantified by temporal PCA of peak‐adjusted CSDs. For words and faces in both paradigms, N1 was substantially reduced in AH compared with NH and HC, who did not differ from each other. The difference in N1 between AH and NH was not due to overall symptom severity or performance accuracy, with both groups showing comparable memory deficits. Our findings extend prior reports of reduced auditory N1 in AH, suggesting a broader early perceptual integration deficit that is not limited to the auditory modality.
High altitude exposure impairs sleep patterns, mood, and cognitive functions
Authors: de Aquino Lemos Valdir , Antunes Hanna Karen Moreira , dos Santos Ronaldo Vagner Thomatieli , Lira Fabio Santos , Tufik Sergio , de Mello Marco Túlio
Published: July 2012

This work evaluated the importance of sleep on mood and cognition after 24 h of exposure to hypoxia. Ten males, aged 23–30 years, were placed in a normobaric chamber simulating an altitude of 4,500 m. Sleep assessments were conducted from 22:00–6:00; all mood and cognitive assessments were performed 20 min after awakening. The assessments were conducted in normoxic conditions and after 24 h of hypoxia. Sleep was reevaluated 14 h after the start of exposure to hypoxic conditions, and mood state and cognitive functions were reevaluated 24 h after the start of exposure to hypoxic conditions. Hypoxia reduced total sleep time, sleep efficiency, slow‐wave sleep, and rapid eye movement. Depressive mood, anger, and fatigue increased under hypoxic conditions. Vigor, attention, visual and working memory, concentration, executive functions, inhibitory control, and speed of mental processing worsened. Changes in sleep patterns can modulate mood and cognition after 24 h.
Association Between Timing of Epinephrine Administration and Intact Neurologic Survival Following Out‐of‐hospital Cardiac Arrest in Japan: A Population‐based Prospective Observational Study
Authors: Nakahara Shinji , Tomio Jun , Nishida Masamichi , Morimura Naoto , Ichikawa Masao , Sakamoto Tetsuya
Published: July 2012

ACADEMIC EMERGENCY MEDICINE 2012; 19:782–792 © 2012 by the Society for Academic Emergency Medicine

Objectives:  This study aimed to investigate whether early epinephrine administration in out‐of‐hospital cardiopulmonary arrest (OHCA) patients was associated with improved outcomes and to address the selection bias inherent in observational studies (more severe cases are more likely to receive epinephrine).

Methods:  This was a retrospective analysis of prospectively collected population‐based data of adult bystander‐witnessed OHCA patients from a nationwide Japanese registry between January 2007 and December 2008. To address selection bias, those who attained early return of spontaneous circulation (ROSC) without epinephrine administration were excluded, leaving 49,165 patients in the analysis. The outcomes were intact neurologic survival, defined as survival with cerebral performance category score 1or 2, and any survival at 1 month or at discharge (whichever was earlier). The primary predictor was the time from the start of cardiopulmonary resuscitation (CPR) by emergency medical services (EMS) to first epinephrine administration, with early epinephrine defined as within 10 minutes.

Results:  Multivariate logistic regression analysis showed that cardiac origin OHCA patients who received early epinephrine (≤10 minutes) had significantly higher rates of intact neurologic survival (odds ratio [OR] = 1.39, 95% confidence interval [CI] = 1.08 to 1.78) and any survival (OR = 1.73, 95% CI = 1.46 to 2.04) than those who did not receive early epinephrine, after adjusting for potential confounders. Results for noncardiac OHCA patients were similar.

Conclusions:  Early epinephrine administration may be associated with higher rates of intact neurologic survival and any survival in adult bystander‐witnessed OHCA patients. This article provides a potential method to address the selection bias inherent in observational studies that examine the effects of drug administration in OHCA patients.
Comparing Least‐squares and Quantile Regression Approaches to Analyzing Median Hospital Charges
Authors: Olsen Cody S. , Clark Amy E. , Thomas Andrea M. , Cook Lawrence J.
Published: July 2012

ACADEMIC EMERGENCY MEDICINE 2012; 19:866–875 © 2012 by the Society for Academic Emergency Medicine

Background:  Emergency department (ED) and hospital charges obtained from administrative data sets are useful descriptors of injury severity and the burden to EDs and the health care system. However, charges are typically positively skewed due to costly procedures, long hospital stays, and complicated or prolonged treatment for few patients. The median is not affected by extreme observations and is useful in describing and comparing distributions of hospital charges. A least‐squares analysis employing a log transformation is one approach for estimating median hospital charges, corresponding confidence intervals (CIs), and differences between groups; however, this method requires certain distributional properties. An alternate method is quantile regression, which allows estimation and inference related to the median without making distributional assumptions.

Objectives:  The objective was to compare the log‐transformation least‐squares method to the quantile regression approach for estimating median hospital charges, differences in median charges between groups, and associated CIs.

Methods:  The authors performed simulations using repeated sampling of observed statewide ED and hospital charges and charges randomly generated from a hypothetical lognormal distribution. The median and 95% CI and the multiplicative difference between the median charges of two groups were estimated using both least‐squares and quantile regression methods. Performance of the two methods was evaluated.

Results:  In contrast to least squares, quantile regression produced estimates that were unbiased and had smaller mean square errors in simulations of observed ED and hospital charges. Both methods performed well in simulations of hypothetical charges that met least‐squares method assumptions. When the data did not follow the assumed distribution, least‐squares estimates were often biased, and the associated CIs had lower than expected coverage as sample size increased.

Conclusions:  Quantile regression analyses of hospital charges provide unbiased estimates even when lognormal and equal variance assumptions are violated. These methods may be particularly useful in describing and analyzing hospital charges from administrative data sets.
Structure‐guided mutagenesis for the improvement of substrate specificity of Bacillus megaterium glucose 1‐dehydrogenase IV
Authors: Nishioka Taiki , Yasutake Yoshiaki , Nishiya Yoshiaki , Tamura Tomohiro
Published: July 2012

Bacillus megaterium IAM 1030 (Bacillus sp. JCM 20016) possesses four d‐glucose 1‐dehydrogenase isozymes (BmGlcDH‐I, ‐II, ‐III and ‐IV) that belong to the short‐chain dehydrogenase/reductase superfamily. The BmGlcDHs are currently used for a clinical assay to examine blood glucose levels. Of these four isozymes, BmGlcDH‐IV has relatively high thermostability and catalytic activity, but the disadvantage of its broad substrate specificity remains to be overcome. Here, we describe the crystal structures of BmGlcDH‐IV in ligand‐free, NADH‐bound and β‐d‐glucose‐bound forms to a resolution of 2.0 Å. No major conformational differences were found among these structures. The structure of BmGlcDH‐IV in complex with β‐d‐glucose revealed that the carboxyl group at the C‐terminus, derived from a neighboring subunit, is inserted into the active‐site pocket and directly interacts with β‐d‐glucose. A site‐directed mutagenic study showed that destabilization of the BmGlcDH‐IV C‐terminal region by substitution with more bulky and hydrophobic amino acid residues greatly affects the activity of the enzyme, as well as its thermostability and substrate specificity. Of the six mutants created, the G259A variant exhibited the narrowest substrate specificity, whilst retaining comparable catalytic activity and thermostability to the wild‐type enzyme.

Database
 The atomic coordinates and structure factor amplitudes for BmGlcDH‐IV in ligand‐free form, in complex with NADH, in complex with d‐glucose, G259A mutant in ligand‐free form, and A258F mutant in complex with d‐glucose and NADH were deposited in the RCSB Protein Data Bank (http://www.rcsb.org) under the accession codes 3AUS, 3AUT, 3AUU, 3AY6 and 3AY7, respectively

Structured digital abstract

 BmGlcDH‐IV and BmGlcDH‐IV bind by x‐ray crystallography (View Interaction: 1, 2)
Proliferation of myogenic stem cells in human skeletal muscle in response to low‐load resistance training with blood flow restriction
Authors: Nielsen Jakob Lindberg , Aagaard Per , Bech Rune Dueholm , Nygaard Tobias , Hvid Lars Grøndahl , Wernbom Mathias , Suetta Charlotte , Frandsen Ulrik
Published: July 2012

Key points

In the last decade muscle training performed using a combination of low external loads and partial restriction of blood flow to the exercising limb has gained increasing interest, since it leads to significant gains in muscle strength and muscle mass.

The cellular mechanisms responsible for the muscular adaptations induced by this training paradigm are not fully understood.

This study shows that 3 weeks of high‐frequency, low‐intensity muscle exercise with partial blood flow restriction induces increases in maximal muscle strength accompanied by highly marked gains in muscle fibre size.

Furthermore, the results indicate that these muscular adaptations rely on a considerable upregulation in myogenic satellite cells number, resulting in nuclear addition to the exercised myofibres.

The results contribute to a better understanding of the physiological mechanisms underlying the gain in muscle strength and muscle mass observed with blood flow restricted low‐intensity resistance exercise.

Abstract  Low‐load resistance training with blood flow restriction has been shown to elicit substantial increases in muscle mass and muscle strength; however, the effect on myogenic stem cells (MSCs) and myonuclei number remains unexplored. Ten male subjects (22.8 ± 2.3 years) performed four sets of knee extensor exercise (20% 1RM) to concentric failure during blood flow restriction (BFR) of the proximal thigh (100 mmHg), while eight work‐matched controls (21.9 ± 3.0 years) trained without BFR (control, CON). Twenty‐three training sessions were performed within 19 days. Maximal isometric knee extensor strength (MVC) was examined pre‐ and post‐training, while muscle biopsies were obtained at baseline (Pre), after 8 days intervention (Mid8) and 3 (Post3) and 10 days (Post10) post training to examine changes in myofibre area (MFA), MSC and myonuclei number. MVC increased by 7.1% (Post5) and 10.6% (Post12) (P < 0.001) with BFR training, while type I and II MFA increased by 38% (Mid8), 35–37% (Post3) and 31–32% (Post10) (P < 0.001). MSCs per myofibre increased with BFR training from 0.10 ± 0.01 (Pre) to 0.38 ± 0.02 (Mid8), 0.36 ± 0.04 (Post3) and 0.25 ± 0.02 (Post10) (P < 0.001). Likewise, myonuclei per myofibre increased from 2.49 ± 0.07 (Pre) to 3.30 ± 0.22 (Mid8), 3.20 ± 0.16 (Post3) and 3.11 ± 0.11 (Post10), (P < 0.01). Although MFA increased in CON at Mid8, it returned to baseline at Post3. No changes in MSC or myonuclei number were observed in CON. This study is the first to show that short‐term low‐load resistance exercise performed with partial blood flow restriction leads to marked proliferation of myogenic stem cells and resulting myonuclei addition in human skeletal muscle, which is accompanied by substantial myofibre hypertrophy.
Improved Finite Element Model to Predict the Reverse Loading Behavior of Autofrettaged A723 and HB7 Cylinders
Authors: Troiano E. , Underwood J. H. , Venter A. M. , Izzo J. H. , Norray J. M.
Published: July 2012

Ideal isotropic or kinematic hardening is often utilized in order to simplify the modeling of the loading and reverse loading behavior of materials when using finite element analysis. Unfortunately, this simplification can result in significant error if the material exhibits the Bauschinger effect (BE), which is the loss of strength of the material upon reverse loading. The error associated with this simplification is further compounded in heavily autofrettaged, Cr-Mo-V, thick walled cylinders due to the fact that the Bauschinger effect and the reverse loading strain hardening exponent are a strong function of the initial applied plastic strains, which can vary significantly throughout the wall of the cylinder.
A Review of Hybrid Solar–Fossil Fuel Power Generation Systems and Performance Metrics
Authors: Sheu Elysia J. , Mitsos Alexander , Eter Ahmad A. , Mokheimer Esmail M. A. , Habib Mohamed A. , Al-Qutub Amro
Published: July 2012

A literature review of hybrid solar–fossil fuel power generation is given with an emphasis on system integration and evaluation. Hybrid systems are defined as those which use solar energy and fuel simultaneously, thus excluding the viable alternative of solar thermal plants which use fossil fuels as backup. The review is divided into three main sections: performance metrics, the different concentrated solar receiver technologies and their operating conditions, and the different hybridization schemes. In addition, a new linear combination metric for analysis of hybrid systems, which considers trade-off of different metrics at the fleet level, is presented. This metric is also compared to alternative metrics from multi-objective optimization. Some previous work only evaluates the hybrid cycle at a certain point in time, which can be misleading as this evaluation would not take into account certain aspects of hybrid cycle, such as fluctuating solar supply. Furthermore, almost all previous work designs the hybrid solar–fossil fuel systems for a certain point in time and then evaluates the performance of the system for an entire year. By not taking into account fluctuating solar supply and selling price of electricity in the design of the system, the best possible annual performance of the hybrid cycle may not be reached.
Silicon recess minimization during gate patterning using synchronous plasma pulsing
Authors: Petit-Etienne Camille , Pargon Erwine , David Sylvain , Darnon Maxime , Vallier Laurent , Joubert Olivier , Banna Samer
Published: July 2012

With the emergence of new semiconductor devices and architectures, there is a real need to limit plasma induced damage. This study clearly demonstrates the capability of pulsed plasma technology to minimize plasma induced silicon oxidation that leads to the silicon recess phenomenon during polysilicon gate patterning. Indeed, the authors show that by pulsing optimized continuous wave overetch plasma conditions using HBr/He/O2 plasmas, the silicon recess is reduced from 0.6 to 0.2 nm, while the gate profiles are maintained anisotropic. Synchronous pulsed plasmas open new paths to pattern complex stacks of ultrathin materials without surface damage.
What causes adverse events in prehospital care? A human-factors approach
Authors: Price Roger , Bendall Jason C , Patterson Jillian A , Middleton Paul M
Published: July 2012

Background

The last decade has seen a vast amount of work directed at the investigation of patient harm events. Unfortunately, little of it has pertained to prehospital care and as such, risk remains unquantified and poorly understood in this setting. We hypothesised that adverse patient events occurring during the prehospital phase may fall into discernible patterns, and that an understanding of these patterns would be valuable in the development of mitigation strategies.

Methods

A survey tool was developed with reference to the human factors literature. Paramedics in a large Australian ambulance service were asked to recall an adverse event and to nominate factors that may have contributed to its occurrence. Responses were analysed using principal components analysis in order to identify contributory factors that could be statistically grouped together in meaningful patterns.

Results

The survey yielded 370 responses. Eight key single contributors and 14 groups of contributory factors were identified. Of the groups, only two were strongly associated with serious patient outcomes, such as reported significant deterioration or death.

Conclusions

The deteriorating patient was identified as the leading single contributor to prehospital adverse events, and two perfect storm patient harm scenarios were found to contribute materially to adverse outcomes. This approach to identifying both single factors contributing to an incident and factors which could be grouped together in a pattern, appears useful in delineating risk in the acute prehospital setting, and warrants further exploration in this and other areas of patient safety.
Reducing inappropriate emergency department attendances—a review of ambulance service attendances at a regional teaching hospital in Scotland
Authors: Patton Gareth Gordon , Thakore Shobhan
Published: July 2012

Introduction

Emergency Departments (ED) in the UK have seen increasing attendance rates in recent years. Departments are now seeking strategies to reduce their attendances. A review of all ambulance attendances to the ED at Ninewells Hospital was conducted to identify if patients presenting by ambulance could be seen and treated more appropriately in other parts of the health service.

Method

A retrospective review of ambulance attendances to the ED at Ninewells Hospital over 7 non-consecutive days. The ambulance patient report form and the ED notes were reviewed by the duty consultant to deem whether it was appropriate for the patient to be presented to the ED. If inappropriate, an alternative destination was suggested. Additional data was collected on the source of the ambulance call.

Results

There were 910 attendances in the 7 days. 295 (32%) presented by ambulance. 32 had incomplete data and were excluded. 185 (70%) and 179 (68%) of the 263 were deemed appropriate from review of the patient report form and notes respectively. Of the inappropriate, 74.4% and 79.7% had primary care suggested as an alternative. Patients who call for their own ambulance and NHS24 had higher rates of inappropriate attendances.

Discussion

The ambulance services present one-third of the patients to the ED at Ninewells Hospital. 30%–32% were found to be attending inappropriately and 74%–80% of these could have been managed in primary care. Reducing inappropriate ambulance attendances could reduce the departmental patient load by 11%.