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Using transient imaging data from the 2nd and 3rd years of the SDSS supernova survey, we apply various machine learning techniques to the problem of classifying transients (e.g. SNe) from artefacts, one of the first steps in any transient detection pipeline, and one that is often still carried out by human scanners. Using features mostly obtained from PCA, we show that we can match human levels of classification success, and find that a K-nearest neighbours algorithm and SkyNet perform best, while the Naive Bayes, SVM and minimum error classifier have performances varying from slightly to significantly worse.
Planet formation and clearing of protoplanetary disks is one of the long standing problems in disk evolution theory. The best test of clearing scenarios is observing systems that are most likely to be actively forming planets: the transitional disks with large inner dust cavities. We present the first results of our ALMA (Atacama Large Millimeter/submillimeter Array) Cycle 0 program using Band 9, imaging the Herbig Ae star Oph IRS 48 in CO 6−5 and the submillimeter continuum in the extended configuration. The resulting ~0.2″ spatial resolution completely resolves the cavity of this disk in the gas and the dust. The gas cavity of IRS 48 is half as large as the dust cavity, ruling out grain growth and photoevaporation as the primary cause of the truncation. On the other hand, the continuum emission reveals an unexpected large azimuthal asymmetry and steep edges in the dust distribution along the ring, suggestive of dust trapping. We will discuss the implications of the combined gas and dust distribution for planet formation at a very early stage. This is one of the first transition disks with spatially resolved gas inside the cavity, demonstrating the superb capabilities of the Band 9 receivers.
In this second of two articles on second messenger/signal transduction cascades in major mood disorders, we will review the evidence in support of intracellular dysfunction and its rectification in the etiopathogenesis and treatment of bipolar disorder (BD). The importance of these cascades is highlighted by lithium's (the gold standard in BD psychopharmacology) ability to inhibit multiple critical loci in second messenger/signal transduction cascades including protein kinase C (involved in the IP3/PIP2 pathway) and GSK-3β (canonically identified in the Wnt/Fz/Dvl/GSK-3β cascade). As a result, and like major depressive disorder (MDD), more recent pathophysiological studies and rational therapeutic targets have been directed at these and other intracellular mediators. Even in the past decade, intracellular dysfunction in numerous neuroprotective/apoptotic cascades appears important in the pathophysiology and may be a future target for pharmacological interventions of BD.
The etiopathogenesis and treatment of major mood disorders have historically focused on modulation of monoaminergic (serotonin, norepinephrine, dopamine) and amino acid [γ-aminobutyric acid (GABA), glutamate] receptors at the plasma membrane. Although the activation and inhibition of these receptors acutely alter local neurotransmitter levels, their neuropsychiatric effects are not immediately observed. This time lag implicates intracellular neuroplasticity as primary in the mechanism of action of antidepressants and mood stabilizers. The modulation of intracellular second messenger/signal transduction cascades affects neurotrophic pathways that are both necessary and sufficient for monoaminergic and amino acid–based treatments. In this review, we will discuss the evidence in support of intracellular mediators in the pathophysiology and treatment of preclinical models of despair and major depressive disorder (MDD). More specifically, we will focus on the following pathways: cAMP/PKA/CREB, neurotrophin-mediated (MAPK and others), p11, Wnt/Fz/Dvl/GSK3β, and NFκB/ΔFosB. We will also discuss recent discoveries with rapidly acting antidepressants, which activate the mammalian target of rapamycin (mTOR) and release of inhibition on local translation via elongation factor stimulation. Throughout this discourse, we will highlight potential intracellular targets for therapeutic intervention. Finally, future clinical implications are discussed.
Tricyclic antidepressant (TCA) overdose is a leading cause of death among intentional overdoses. Intravenous lipid emulsion therapy is an emerging antidote for local anesthetic toxicity, and there is animal evidence that lipid therapy may be efficacious in TCA overdose. Furthermore, case reports in humans have described the use of lipid therapy to reverse the toxicity of other lipophilic drugs. Here we report a 25-year-old female presenting with coma and hemodynamic instability following intentional ingestion of amitriptyline. She had multiple episodes of pulseless wide-complex tachycardia despite conventional treatment with chest compressions, cardioversion, lidocaine, epinephrine, norepinephrine, magnesium sulphate, sodium bicarbonate, activated charcoal, and whole bowel irrigation. Twenty percent lipid emulsion was administered intravenously (an initial 150 mL bolus, followed by an infusion at 16 mL/h and a second bolus of 40 mL) over 39 hours (total dose 814 mL) yet resulted in no dramatic changes in hemodynamics or level of consciousness. However, there was a decrease in the frequency of wide-complex tachycardia during the lipid emulsion infusion and a recurrence of wide-complex tachycardia shortly after the infusion was stopped. The patient was discharged from the intensive care unit 11 days later with no lasting physiologic sequelae.
The diameter of the pupil is affected by changes in ambient illumination, color, spatial structure, movement, and mental effort. It has now been found that pupil diameter can be affected by cognitive processes. That is, it can be entrained by alternations between broadly spread and narrowly focused attention that are cued exogenously (attention is “summoned” by the cue) or endogenously (attention changes under the perceiver’s intentional control). Pupil diameter also is affected by post-eye-blink constrictions that occur most often when attention is narrowed, and possibly by changes evoked by the near reflex, although changes in attention state parsimoniously account for the entirety of the results. Changes in pupil diameter produce differences in spherical aberration that alternately blur (when the pupil dilates) and sharpen the retinal image (when the pupil constricts), affecting the relative sensitivity of large receptive fields that mediate broadly spread attention compared with smaller receptive fields that mediate more narrowly focused attention. Results for endogenously cued, intentional changes in attentional spread provide definitive behavioral evidence for cortical feedback to subcortical nuclei that control pupil diameter, either directly or through pupil-constricting eye blinks. Analyses of convergent and divergent changes in eye position indicate that the near reflex was activated long after the initiation of relatively gradual attentionally cued changes in pupil diameter, and further, that when it occurs, the near reflex facilitates ongoing changes in pupil diameter.
Tensile deformation and fracture properties of several metallic materials, welds, and their heataffected-zones were determined non-destructively using the Stress-Strain Microprobe (SSM) system. The system is based on automated ball indentation (ABI) technique and involves straincontrolled multiple indentations at the same location on the material surface by a small spherical indenter. The technique permits evaluation of tensile deformation parameters such as yield strength, ultimate tensile strength, strength coefficient, and strain-hardening exponent, and a fracture energy parameter called indentation energy to fracture. ABI tests were conducted on carbon steels, stainless steels, nickel alloys, aluminum alloys, Zircaloys, electronic soldering materials and several nuclear pressure vessel steels (in the unirradiated, neutron irradiated, and irradiated and thermally annealed conditions). For all these test materials and conditions, the ABI-derived results were found to agree with the data from conventional standard test methods. In addition to the laboratory applications of SSM, it can be used as an in-situ testing instrument for non-destructive assessment of deformation and fracture properties of operating structural components.
This article reviews the development of nonpolar and semipolar InGaN/GaN light-emitting diodes (LEDs), emphasizing structures on freestanding bulk GaN. A brief history of LED development on each orientation is provided, followed by a discussion of the most relevant and recent results. The context is related to several current LED issues, such as the realization of high-efficiency white solid-state lighting, potential solutions to the “green gap,” and applications for polarized emitters. The section on nonpolar LEDs highlights high-power violet and blue emitters and considers the effects of indium incorporation and substrate miscut. The section on semipolar GaN reviews the development of LEDs in the violet, blue, green, and yellow regions and highlights the potential of InGaN/GaN LEDs as an alternative technology to AlInGaP for yellow emitters. A brief review of polarization anisotropy also is included for each orientation. Finally, a two source white light system utilizing a nonpolar blue LED and a semipolar yellow LED is presented.
Objective: Point-of-care testing (POCT) devices are deployed in the field for emergency on-site testing under a wide range of environmental conditions. Our objective was to evaluate the performance of glucose meter test strips and handheld blood gas analyzer cartridges following thermal stresses that simulate field conditions.
Methods: We evaluated electrochemical and spectrophotometric glucose meter systems and a handheld blood gas analyzer. Glucose test strips were cold-stressed (–21°C) and heat-stressed (40°C) for up to 4 weeks. Blood gas cartridges were stressed at –21°C, 2°C, and 40°C for up to 72 hours. Test strip and cartridge performance was evaluated using aqueous quality control solutions. Results were compared with those obtained with unstressed POCT strips and cartridges.
Results: Heated glucose test strips and blood gas cartridges yielded elevated results. Frozen test strips and cooled cartridges yielded depressed glucose and blood gas results, respectively. Frozen cartridges failed.
Conclusions: The performance of glucose test strips and blood gas cartridges was affected adversely by thermal stresses. Heating generated elevated results, and cooling depressed results. Disaster medical assistance teams and emergency medical responders should be aware of these risks. Field POCT devices must be robust to withstand adverse conditions. We recommend that industry produce POCT devices and reagents suitable for disaster medical assistance teams. (Disaster Med Public Health Preparedness. 2009;3:13–17)
We inoculated pasteurized whole milk with Escherichia coli strains GC4468 (intact marRAB locus), JHC1096 (Δ marRAB), or AG112 (Δ marR), and incubated each overnight at 37°C. All strains were then recovered from the milk cultures, and susceptibilities to antimicrobial agents were determined by the E-test strip method (CLSI). Cells of strain GC4468, prior to culturing in milk, were susceptible to trimethoprim, gatifloxacin, cefotaxime and tetracycline. After culturing GC4468 in pasteurized milk, however, the minimal inhibitory concentrations (MICs) increased 1·4-fold for trimethoprim (P⩽0·05), 1·5-fold for gatifloxacin (P⩽0·05), 2·0-fold for cefotaxime (P=0·008), and 1·4-fold for tetracycline (P⩾0·05). After culturing GC4468 on milk count agar the MICs were enhanced 3·4-fold for trimethoprim (P⩽0·05), 10-fold for gatifloxacin (P=0·001), 7·1-fold for cefotaxime (P=0·011), and 40·5-fold for tetracycline (P=0·074), but exhibiting tetracycline resistance with a mean MIC of 74·7±18·47 μg/ml (CLSI). The MICs of the antimicrobial agents for JHC1096 cells after culturing in pasteurized whole milk were indistinguishable (P⩾0·05) from baseline MICs measured before culturing in the same type of milk. Thus, Esch. coli cells harbouring the marRAB locus exhibit reduced susceptibilities to multiple antimicrobial agents after culturing in pasteurized whole milk.
We performed genome-wide chemical mutagenesis of C57BL/6J mice
using N-ethyl-N-nitrosourea (ENU). Electroretinographic
screening of the third generation offspring revealed two G3 individuals
from one G1 family with a normal a-wave but lacking the b-wave that we
named nob4. The mutation was transmitted with a recessive mode of
inheritance and mapped to chromosome 11 in a region containing the
Grm6 gene, which encodes a metabotropic glutamate receptor
protein, mGluR6. Sequencing confirmed a single nucleotide substitution
from T to C in the Grm6 gene. The mutation is predicted to result
in substitution of Pro for Ser at position 185 within the extracellular,
ligand-binding domain and oocytes expressing the homologous mutation in
mGluR6 did not display robust glutamate-induced currents. Retinal mRNA
levels for Grm6 were not significantly reduced, but no
immunoreactivity for mGluR6 protein was found. Histological and fundus
evaluations of nob4 showed normal retinal morphology. In
contrast, the mutation has severe consequences for visual function. In
nob4 mice, fewer retinal ganglion cells (RGCs) responded to the
onset (ON) of a bright full field stimulus. When ON responses could be
evoked, their onset was significantly delayed. Visual acuity and contrast
sensitivity, measured with optomotor responses, were reduced under both
photopic and scotopic conditions. This mutant will be useful because its
phenotype is similar to that of human patients with congenital stationary
night blindness and will provide a tool for understanding retinal
circuitry and the role of ganglion cell encoding of visual
We investigated attentional outcome after childhood stroke and
orthopedic diagnosis in medical controls. Twenty-nine children with
focal stroke lesions and individually matched children with clubfoot or
scoliosis were studied with standardized attention and neuroimaging
assessments. Stroke lesions were quite varied in location and commonly
involved regions implicated in Posner's model of attention
networks. Children with stroke lesions performed significantly more
poorly regarding attention function compared with controls. Performance
on the Starry Night, a test demanding alerting and sensory-orienting
but not executive attention function, was significantly associated with
lesion size in the alerting and sensory-orienting networks but not the
executive attention network. Furthermore, earlier age at lesion
acquisition was significantly associated with poorer attention function
even when lesion size was controlled. These findings support the theory
of dissociable networks of attention and add to evidence from studies
of children with diffuse and focal brain damage that early insults are
associated with worse long-term outcomes in many domains of
neuropsychological function. In addition, these results may provide
clues towards the understanding of mechanisms underlying attention in
children. (JINS, 2004, 10, 976–986.)
The archaeological record, as well as written texts, oral traditions,
and iconographic representations, express the Maya perception of cosmic
order, including the concepts of quadripartite division and layered
cosmos. The ritual act of portioning and layering created spatial order
and was used to organize everything from the heavens to the layout of
altars. These acts were also metaphors for world creation, world order,
and establishing the center as a position of power and authority. This
article examines the articulations of these concepts from the level of
caches to the level of regions from the past and present in an attempt
to understand these ancient perceptions. We emphasize that basic
organizational notions of the cosmos permeate all societal levels and
argue that scholars should expand their focus to include how the sacred
landscape and its related ideology were reproduced in the lives of
We investigated the frequency and neurocognitive correlates of
attention deficit hyperactivity disorder and traits of this disorder
(ADHD/Traits) after childhood stroke and orthopedic diagnosis in
medical controls. Twenty-nine children with focal stroke lesions and
individually matched children with clubfoot or scoliosis were studied
with standardized psychiatric, intellectual, academic, adaptive,
executive, and motivation function assessments. Lifetime
ADHD/Traits were significantly more common in stroke participants
with no prestroke ADHD than in orthopedic controls (16/28
vs. 7/29; Fisher's Exact p < .02).
Lifetime ADHD/Traits in the orthopedic controls occurred
exclusively in males with clubfoot (7/13; 54%). Participants with
current ADHD/Traits functioned significantly worse (p <
.005) than participants without current ADHD/Traits on all outcome
measures. Within the stroke group, current ADHD/Traits was
associated with significantly lower verbal IQ and arithmetic
achievement (p < .04), more nonperseverative errors
(p < .005), and lower motivation (p < .004). A
principal components analysis of selected outcome variables
significantly associated with current ADHD/Traits revealed
“impaired neurocognition” and
“inattention-apathy” factors. The latter factor was a more
consistent predictor of current ADHD/Traits in regression analyses.
These findings suggest that inattention and apathy are core features of
ADHD/Traits after childhood stroke. This association may provide
clues towards the understanding of mechanisms underlying the syndrome.
(JINS, 2003, 9, 815–829.)
Methods used to quantify the stress response in animals are vital tools in many areas of biology. Here we describe a new method of measuring the stress response, which provides rapid results and can be used in the field or laboratory. After a stressful event, we measure the capacity of circulating leukocytes to produce a respiratory burst in vitro in response to challenge by phorbol myristate acetate (PMA). During the respiratory burst leukocytes produce oxygen free radicals, and the level of production can be measured directly as chemiluminescence. When in vitro PMA-stimulated whole blood chemiluminescence is measured directly after a stressful event, we define the response as the leukocyte coping capacity (LCC). In an experiment badgers (Meles meles), which were caught as part of an on-going population study, were either transported to a central site prior to blood sampling or blood was collected at their site of capture. Transported animals had a significantly lower LCC and showed changes in leukocyte composition that were indicative of stress. We conclude that the stress of transport reduced LCC in badgers and that LCC serves as a quantitative measure of stress. Potential applications of this method are discussed. Experimental Physiology (2003) 88.4, 541-546.
We used polymorphic microsatellite markers to look for recombination during parthenogenetic oogenesis between the X chromosomes of aphids of the tribe Macrosiphini. We examined the X chromosome because it comprises ∼25% of the genome and previous cytological observations of chromosome pairing and nucleolar organizer (NOR) heteromorphism suggest recombination, although the same is not true for autosomes. A total of 564 parthenogenetic females of Myzus clones with three distinct reproductive modes (cyclical parthenogenesis, obligate parthenogenesis and obligate parthenogenesis with male production) were genotyped at three informative X-linked loci. Also, parthenogenetically produced males from clones encompassing the full range of male-producing reproductive strategies were genotyped. These included 391 Myzus persicae males that were genotyped at three X-linked loci and 538 males from Sitobion clones that were genotyped at five informative X-linked loci. Our results show no departure from clonality in parthenogenetic generations of aphids of the tribe Macrosiphini: no recombinant genotypes were observed in parthenogenetically produced males or females.
Most aphids are cyclic parthenogens, so are ideal models in studies of the mechanisms and consequences of sex and recombination. However, owing to a shortage of physical and genetic markers, there have been few studies of the most fundamental genetic processes in these organisms. For example, it is not known whether autosomal segregation during male spermatogenesis is in Mendelian proportions: we address that question here. The aphid Myzus persicae has a typical karyotype of 2n = 12 in females (XX), while males are XO (2n = 11). During male meiosis, only the spermatocytes with an X chromosome are viable. We hypothesized that assortment of autosomes might be non-random because chromosomal imprinting leading to elimination of the paternal autosomes is seen in the closely related coccoids. In other aphid models, we have observed segregation distortions at single microsatellite loci (Wilson, 2000). Such distortions may have nothing to do with ‘selfish’ behaviour, but may be caused by mutation accumulation causing fitness differentials. Thus single-locus distortions might be predicted to be more likely to be detected via the male lines of clones that have lost the ability to reproduce sexually (male-producing obligate parthenogenesis (androcyclic)). Using microsatellites we show that genetic imprinting or selfish autosome behaviour does not occur in male M. persicae. Generally, loci segregated in Mendelian proportions in both sexes of cyclically parthenogenetic (holocyclic) clones. However, in androcyclic clones, segregation distortions consistently involved the same two autosomes. This is consistent with linkage of markers to deleterious mutations associated with a loss of sexual reproduction.