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In this paper I survey a range of trolling behaviors and analyze a particular species that stands out. After a brief discussion of some of the inherent challenges in studying internet speech, I describe a few examples of behaviors commonly described as 'trolling' in order to identify what they have in common. I argue that most of these behaviors already have well-researched offline counterparts. In contrast, in the second half of the paper I argue that so-called 'subcultural trolling' calls out for further analysis: it cannot be fully explained using standard tools like insincerity or bullshit, or even using new tools like dogwhistling. Instead, I propose a new species of speech act force. I conclude by highlighting some implications for broader issues in pragmatics and ethics. [ABSTRACT FROM AUTHOR]

We investigated the effects of two types of competition, races and tournaments (as well as an individual challenge and a do-your-best condition), on two different aspects of performance: effort and strategy. In our experiment, 100 undergraduate participants completed a simple cognitive task under four experimental conditions (in a repeated-measures design) based on different types of competitions and challenges. We used the Linear Ballistic Accumulator to quantify the effects of competition on strategy and effort. The results reveal that competition produced changes in strategy rather than effort, and that trait competitiveness had minimal impact on how people responded to competition. This suggests individuals are more likely to adjust their strategy in competitions, and the uncertainty created by different competition types influences the direction of these strategy adjustments. [ABSTRACT FROM AUTHOR]

We examine the underlying cognitive mechanisms that govern how competitions play out over time. We used cognitive modeling to examine the dynamic effects of time remaining and relative performance (whether the person is winning or losing) on effort and strategy. In this experiment, participants completed a competitive decision-making task with varying time limits and starting scores, in a repeated-measures design. Participants were tasked with scoring more points than their computerized opponent during a certain time frame, gaining and losing points for correct and incorrect decisions, respectively. The results showed that as the competition deadline approached and as participants drew ahead of their opponent within a competition, they increased effort and became more cautious. Furthermore, the effect of relative score on effort and caution changed over the course of a competition as the deadline approached. These results highlight the importance of considering dynamics when working to understand how competitions unfold as well as the underlying cognitive mechanisms that give rise to the dynamic behavior. [ABSTRACT FROM AUTHOR]

Cell–cell signaling in microorganisms is still poorly characterized. In this Methods paper, we describe a genetic procedure for detecting cell-nonautonomous genetic effects, and in particular cell–cell signaling, termed the chimeric colony assay (CCA). The CCA measures the effect of a gene on a biological response in a neighboring cell. This assay can measure cell autonomy for range of biological activities including transcript or protein accumulation, subcellular localization, and cell differentiation. To date, the CCA has been used exclusively to investigate colony patterning in the budding yeast Saccharomyces cerevisiae. To demonstrate the wider potential of the assay, we applied this assay to two other systems: the effect of Grr1 on glucose repression of GAL1 transcription in yeast and the effect of rpsL on stop-codon translational readthrough in Escherichia coli. We also describe variations of the standard CCA that address specific aspects of cell–cell signaling, and we delineate essential controls for this assay. Finally, we discuss complementary approaches to the CCA. Taken together, this Methods paper demonstrates how genetic assays can reveal and explore the roles of cell–cell signaling in microbial processes. [ABSTRACT FROM AUTHOR]

Reports of P. vivax infections among Duffy-negative hosts have accumulated throughout sub-Saharan Africa. Despite this growing body of evidence, no nationally representative epidemiological surveys of P. vivax in sub-Saharan Africa have been performed. To overcome this gap in knowledge, we screened over 17,000 adults in the Democratic Republic of the Congo (DRC) for P. vivax using samples from the 2013-2014 Demographic Health Survey. Overall, we found a 2.97% (95% CI: 2.28%, 3.65%) prevalence of P. vivax infections across the DRC. Infections were associated with few risk-factors and demonstrated a relatively flat distribution of prevalence across space with focal regions of relatively higher prevalence in the north and northeast. Mitochondrial genomes suggested that DRC P. vivax were distinct from circulating non-human ape strains and an ancestral European P. vivax strain, and instead may be part of a separate contemporary clade. Our findings suggest P. vivax is diffusely spread across the DRC at a low prevalence, which may be associated with long-term carriage of low parasitemia, frequent relapses, or a general pool of infections with limited forward propagation. Plasmodium vivax generally accounts for a low proportion of malaria cases in Africa, but population-level data on the distribution of infections is limited. Here, the authors use data from the Democratic Republic of the Congo and show that the prevalence is low (~3%) and diffusely spread. [ABSTRACT FROM AUTHOR]

This article aims to propose a theoretical framework, based on the literature, that supports the growth of students' physical literacy in physical education. The framework features a trained educator who seeks to establish a positive climate for learning based on the creation of a positive culture of movement. It features meaningful student experiences, empowers students and staff, and integrates curriculum. Critical attributes from physical literacy theory are seamlessly integrated and nurtured in all four domains: physical, cognitive, behavioral, and affective. [ABSTRACT FROM AUTHOR]

The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations. The genome of the malaria parasite Plasmodium falciparum contains a record of past evolutionary forces. Here, using 2537 parasite sequences from the Democratic Republic of the Congo, the authors demonstrate how drug pressure and human movement have shaped the present-day parasite population. [ABSTRACT FROM AUTHOR]

Ultrafast X-ray imaging on individual fragile specimens such as aerosols [1], metastable particles [2], superfluid quantum systems [3] and live biospecimens [4] provides high-resolution information that is inaccessible with conventional imaging techniques. Coherent X-ray diffractive imaging, however, suffers from intrinsic loss of phase, and therefore structure recovery is often complicated and not always uniquely defined [4], [5]. Here, we introduce the method of in-flight holography, where we use nanoclusters as reference X-ray scatterers to encode relative phase information into diffraction patterns of a virus. The resulting hologram contains an unambiguous three-dimensional map of a virus and two nanoclusters with the highest lateral resolution so far achieved via single shot X-ray holography. Our approach unlocks the benefits of holography for ultrafast X-ray imaging of nanoscale, non-periodic systems and paves the way to direct observation of complex electron dynamics down to the attosecond timescale. Femtosecond X-ray Fourier holography imaging with record-high lateral resolution below 20 nm is demonstrated. Phase information is encoded into the interference of the diffraction patterns of a reference particle with a measurement sample. [ABSTRACT FROM AUTHOR]

The article discusses databases, analysis tools, and other informatics resources related to the use of the Collaborative Cross (CC) and complementary Diversity Outbred (DO) population of mice for analyzing genetic and molecular networks underlying complex traits like mouse behavior. It focuses on computational tools used for genetic mapping and analyzing CC and DO genomes. It also focuses on how these tools help in getting a comprehensive view of the polymorphism segregation in CC and DO mice.

The article discusses the 28th International Mammalian Genome Conference (IMGC) that was held from October 26-29, 2014 in Bar Harbor, Maine. Topics include the bioinformatic workshops, the highlights on mammalian models which are useful in human genetics and research on diseases, and the award to travel scholarships which aims to mentor young scientists. It also mentioned the student satellite symposium held at the auditorium of The Jackson Laboratory.

Inflammatory bowel disease (IBD) is an immune-mediated condition driven by improper responses to intestinal microflora in the context of environmental and genetic background. GWAS in humans have identified many loci associated with IBD, but animal models are valuable for dissecting the underlying molecular mechanisms, characterizing environmental and genetic contributions and developing treatments. Mouse models rely on interventions such as chemical treatment or introduction of an infectious agent to induce disease. Here, we describe a new model for IBD in which the disease develops spontaneously in 20-week-old mice in the absence of known murine pathogens. The model is part of the Collaborative Cross and came to our attention due to a high incidence of rectal prolapse in an incompletely inbred line. Necropsies revealed a profound proliferative colitis with variable degrees of ulceration and vasculitis, splenomegaly and enlarged mesenteric lymph nodes with no discernible anomalies of other organ systems. Phenotypic characterization of the CC011/Unc mice with homozygosity ranging from 94.1 to 99.8 % suggested that the trait was fixed and acted recessively in crosses to the colitis-resistant C57BL/6J inbred strain. Using a QTL approach, we identified four loci, Ccc1, Ccc2, Ccc3 and Ccc4 on chromosomes 12, 14, 1 and 8 that collectively explain 27.7 % of the phenotypic variation. Surprisingly, we also found that minute levels of residual heterozygosity in CC011/Unc have significant impact on the phenotype. This work demonstrates the utility of the CC as a source of models of human disease that arises through new combinations of alleles at susceptibility loci. [ABSTRACT FROM AUTHOR]

Recent advances in immunohistochemical techniques have made it possible to identify micrometastasis using antibodies to cytokeratins (CK). The aim of the study was to determine the prevalence and prognostic significance of immunohistochemically detected micrometastasis (IHM) in patients with localised colorectal cancer (CRC) (Dukes’ A and B). A further aim was to study the prognostic role of histopathological factors such as vascular invasion. The original histology of 168 consecutive patients with Dukes’ A or B tumours who had undergone curative resection was reviewed. Immunohistochemical staining was performed using CK antibodies, AE1/AE3 and MNF116 on all ( n=898) lymph nodes. Survival analysis was performed on 105 cases that had been followed up until death or for at least 5 years. IHM were detected in 17.3% of lymph nodes analysed. Adverse outcome (death/local recurrence) was recorded in 8/49 (16%) patients with IHD-positive nodes and in 10/56 (18%) patients negative for IHM. IHM was not associated with adverse outcome on either univariate ( p=0.540) or multivariate analyses ( p=0.673). There was no correlation of IHM with age, gender, site, size and grade of tumour, depth of tumour invasion or perineural and vascular invasion. Vascular invasion was the only independent prognostic factor identified. We have shown that isolated CK-positive epithelioid cells are commonly found in morphologically benign pericolic lymph nodes of patients with localised (Dukes’ A or B) CRC. These cells may represent occult micrometastasis but are not clinically significant. Vascular invasion identifies patients with localised CRC likely to develop recurrences or die of disease. [ABSTRACT FROM AUTHOR]

Rats selectively bred for high saccharin (HiS) intake consume more alcohol and acquire intravenous (i.v.) cocaine self-administration more rapidly than their low saccharin (LoS)-consuming counterparts. The present experiment was designed to determine whether HiS and LoS rats differed in other aspects of drug abuse. The purpose of the present experiment was to use a two-lever dose self-selection procedure to investigate the regulation/dysregulation of i.v. cocaine self-administration in female HiS and LoS rats. HiS and LoS rats were trained to self-administer eight different doses of cocaine during daily 5-h sessions, with the cocaine doses ranging from 0.2 to 1.6 mg/kg in steps of 0.2 mg/kg. The dose size increased after a response on one lever (infusion duration lengthened by 3 s) and decreased after a response on the other lever (infusion duration shortened by 3 s), with a lower limit of 0 s and with an upper limit of 24 s (a corresponding range of 0 to 1.6 mg/kg); the animals increased or decreased their self-administered dose in nine discrete steps. The HiS rats showed less precise regulation of their postinfusion interval (PII) than LoS rats based on the size of the previously self-administered cocaine dose. Correlations between these variables were lower for HiS than for LoS rats during the acquisition and maintenance phases, and HiS rats had lower PIIs than LoS rats after many of the cocaine doses. The HiS rats also self-administered significantly more cocaine infusions during the maintenance phase than the LoS rats, especially at the highest dose. These data indicate that HiS rats are more likely to self-administer more cocaine infusions, at higher doses, and with less precise dose-time regulation than LoS rats. Thus, rats selectively bred for HiS showed less inhibitory control over their cocaine intake than LoS rats, suggesting that a genetic predisposition for saccharin preference is related to the rewarding effects of i.v. cocaine. [ABSTRACT FROM AUTHOR]

Rats selectively bred for high saccharin (HiS) intake consume more alcohol, acquire intravenous (i.v.) cocaine self-administration more rapidly, and show more dysregulated patterns of cocaine selfadministration than their low saccharin-consuming (LoS) counterparts. Objectives: The purpose of the present study was to determine whether HiS and LoS rats also differ in the escalation, maintenance, extinction, and reinstatement of i.v. cocaine self-administration. Materials and methods: Two experiments were conducted in separate groups of rats. In the first experiment, HiS and LoS female rats were allowed to self-administer cocaine [0.4 mg/kg; fixed ratio (FR) 1] under short (ShA, 2 h per day) or long (LgA, 12 h per day) access conditions for 21 days. Session lengths were subsequently equated (2 h), and FR1-maintained cocaine self-administration was examined. In the second experiment, additional groups of HiS and LoS female rats were given access to cocaine (0.4 mg/kg; FR 1) self-administration during 2-h sessions for 10 days. Subsequently, saline was substituted for cocaine, and responding was extinguished. After a 14- day extinction period, saline- and cocaine-[5, 10, and 15 mg/kg, intraperitoneal (i.p.)] induced reinstatement of drug-seeking behavior was measured. Results: HiS LgA rats escalated their cocaine intake more rapidly than LoS rats, and during the 2 h sessions after escalation cocaine self-administration was significantly higher in HiS LgA rats, compared to LoS LgA rats. HiS rats responded on the cocaine-paired lever more than LoS rats during maintenance, extinction, and cocaine-(15 mg/kg) induced reinstatement. Conclusions: These results suggest that HiS and LoS rats have distinct drug-seeking and drugtaking profiles. The HiS and LoS rats differ along a wide range of behavioral dimensions and represent an important model to study the interactions of excessive intake of dietary substances and vulnerability to drug abuse. [ABSTRACT FROM AUTHOR]

Antagonistic coevolution between hosts and parasites in spatially structured populations can result in local adaptation of parasites; that is, the greater infectivity of local parasites than foreign parasites on local hosts. Such parasite specialization on local hosts has implications for human health and agriculture. By contrast with classic single-species population-genetic models, theory indicates that parasite migration between subpopulations might increase parasite local adaptation, as long as migration does not completely homogenize populations. To test this hypothesis we developed a system-specific mathematical model and then coevolved replicate populations of the bacterium Pseudomonas fluorescens and a parasitic bacteriophage with parasite only, with host only or with no migration. Here we show that patterns of local adaptation have considerable temporal and spatial variation and that, in the absence of migration, parasites tend to be locally maladapted. However, in accord with our model, parasite migration results in parasite local adaptation, but host migration alone has no significant effect. [ABSTRACT FROM AUTHOR]

Presents a study on sex differences in the escalation of oral phencyclidine self-administration under fixed-ratio and progressive-ratio schedules in rhesus monkeys. Factors that determines escalation of drug self-administration; Procedure used in the study; Study findings.

Rationale: Rats selectively bred for high saccharin (HiS) intake consume more alcohol and acquire intravenous (IV) cocaine self-administration more rapidly than their low saccharin (LoS) consuming counterparts. Objectives: The purpose of the present study was to determine whether HiS and LoS rats also differ in the escalation, maintenance, and reinstatement of IV cocaine self-administration. Methods: LoS and HiS female rats were allowed to self-administer cocaine [0.4 mg/kg; fixed ratio (FR) 1] under short (ShA, 2 h per day) or long (LgA, 12 h per day) access conditions for 21 days. Session lengths were subsequently equated (2 h) and (1) FR1-maintained cocaine (0.4 mg/kg) self-administration, (2) progressive ratio (PR)-maintained cocaine (0.2-1.6 mg/kg) self-administration, and (3) saline-induced and cocaine (10 mg/kg, IP)-induced reinstatement of drug-seeking behavior were examined. Results: HiS LgA rats escalated their cocaine intake more rapidly and self-administered more cocaine (mg/kg) than LoS LgA rats; however, there was no LoS versus HiS phenotype difference in the number of infusions self-administered by Day 21. Post-escalation cocaine self-administration under an FR1 schedule did not differ as a function of phenotype (LoS versus HiS) or access condition (ShA versus LgA); however, LoS rats responded more for cocaine under the PR schedule than HiS rats, and they showed a greater reinstatement of cocaine-seeking behavior than HiS rats. In contrast, ShA versus LgA did not affect PR or reinstatement performance in the LoS and HiS groups. Conclusions: These results suggest that LoS and HiS rats have distinct drug-seeking and drug-taking profiles that differ as a function of the experimental phase and access condition. The LoS and HiS rats differ along a wide range of behavioral dimensions and represent an important model to study the interactions of feeding, emotionality, and other factors related to vulnerability to drug abuse. [ABSTRACT FROM AUTHOR]

Multiple G protein-linked neurotransmitter systems have been implicated in the behavioral effects of cocaine. While actions of certain neurotransmitter receptor subtypes and transporters have been identified, the role of individual G protein-regulated enzymes and ion channels in the effects of cocaine remains unclear. Here, we assessed the contribution of G protein-gated, inwardly rectifying potassium (Kir3/GIRK) channels to the locomotor-stimulatory and reinforcing effects of cocaine using knockout mice lacking one or both of the key neuronal channel subunits, Kir3.2 and Kir3.3. Cocaine-stimulated increases in horizontal locomotor activity in wild-type, Kir3.2 knockout, Kir3.3 knockout, and Kir3.2/3.3 double knockout mice, with only minor differences observed between the mouse lines. In contrast, Kir3.2 and Kir3.3 knockout mice exhibited dramatically reduced intravenous self-administration of cocaine relative to wild-type mice over a range of cocaine doses. Paradoxically, Kir3.2/3.3 double knockout mice self-administered cocaine at levels significantly higher than either single knockout alone. These findings suggest that Kir3 channels play significant and complex roles in the reinforcing effect of cocaine. [ABSTRACT FROM AUTHOR]

Background. Many studies have found that the intraocular pressure (IOP) is lower in glaucomatous populations than in normal groups. An alternative method of analysis, commonly used in the investigation of arterial blood pressure, is to reduce the pulse waveform to its component Fourier parts. The purpose of this study, therefore, was to determine whether such a technique is applicable to the IOP pulse and to investigate whether it was superior at differentiating diseased from healthy eyes. Methods. Using a pneumatonometer, continuous 10-s IOP recordings were taken from 10 glaucoma patients and 10 normal subjects. The IOP recordings were then analysed using the fast Fourier transform (FFT) to determine their spectral components. In addition, standard IOP parameters (pulse amplitude, pulse volume, and pulsatile ocular blood flow) were measured to allow comparison with the waveform analysis technique. Results. Analysis by FFT successfully determined the IOP pulse's higher spectral components up to the fourth harmonic. In addition, although standard measurements of the IOP pulse (such as pulse amplitude) were insignificant, the second ( P=0.034), third ( P=0.015) and fourth ( P=0.013) harmonics of the waveform successfully differentiated between the glaucoma and normal groups. Conclusion. Spectral analysis of the IOP pulse appears to be a promising technique in the investigation of ocular vascular disease. [ABSTRACT FROM AUTHOR]

Rationale: Rats selectively bred for high intake of a sweet saccharin solution (HiS) consume more ethanol than their low-saccharin intake (LoS) counterparts. The HiS phenotype may be a predictor of abuse of other drugs via other routes of administration. Objective: HiS and LoS, male and female rats were tested for acquisition of IV cocaine and heroin self-administration under a fixed-ratio 1 (FR1) schedule, and cocaine-reinforced behavior was examined under a progressive-ratio (PR) schedule. Methods: Four groups of rats (HiS males and females and LoS males and females) were trained to self-administer IV cocaine (0.2 mg/kg), and another four groups were trained to self-administer heroin (0.015 mg/kg) using an automated autoshaping procedure. Rats were allowed 30 days to reach a criterion whereby a mean of 100 (cocaine) or 20 (heroin) infusions were self-administered during 6-h sessions over 5 consecutive days. Results: The HiS female rats acquired cocaine self-administration significantly more rapidly than the LoS rats, and females of both phenotypes met the acquisition criteria more rapidly than males. In both HiS and LoS cocaine groups a greater percentage of females (compared with males) met the acquisition criteria within 30 days. The only cocaine group in which 100% met the criterion was the HiS females. The female (compared with male) heroin groups showed a more rapid rate of acquisition, but there was no difference due to saccharin phenotype. In each of the four heroin groups 100% of all rats met the criteria within 30 days. Results of the PR schedule in the HiS females and males and LoS females indicated significantly higher break points in the HiS females (compared with HiS males), but there were no differences in females due to phenotype. Conclusion: Female rats selectively bred for higher saccharin intake show more rapid and successful acquisition of IV self-administration of a low dose of cocaine than those bred for low saccharin intake. Female rats... [ABSTRACT FROM AUTHOR]

The plant defensin PDF1.2 has previously been shown to accumulate systemically via a salicylic acid-independent pathway in leaves of Arabidopsis upon challenge by fungal pathogens. To further investigate the signalling and transcriptional processes underlying plant defensin induction, a DNA fragment containing 1184 bp and 1232 bp upstream of the transcriptional and translational start sites, respectively, was cloned by inverse PCR. To test for promoter activity this DNA fragment was linked to the β-glucuronidase (GUS)-encoding region of the UidA gene as a translational fusion and introduced into Arabidopsis ecotype C-24. Challenge of the transgenic plants with the fungal pathogens Alternaria brassicicola and Botrytis cinerea resulted in both local and systemic induction of the reporter gene. Wounding of the transgenic plants had no effect on GUS activity. Treatment of the transgenic plants with either jasmonates or the active oxygen generating compound paraquat strongly induced the reporter gene. In contrast, neither salicylate nor its functional analogues 2,6-dichloroisonicotinic acid and 1,2,3-benzothiodiazole-7-carbothioic acid S-methyl ester resulted in reporter gene induction. These results are consistent with the existence of a salicylic acid-independent signalling pathway, possibly involving jasmonates as regulators, that is triggered by pathogen challenge but not by wounding. The transgenic plants containing the PDF1.2-based promoter-reporter construct will provide useful tools for future genetic dissection of this novel systemic signalling pathway. [ABSTRACT FROM AUTHOR]

Evaluation of in utero shunting for fetal ventriculomegaly requires an analysis of the ex utero treatment of a comparison population of infants with idiopathic aqueductal stenosis (IAS). In this study, 14 neonates with IAS were followed with detailed developmental assessment profiles for 18 months or longer. Using magnetic resonance imaging, the preoperative and postoperative frontal cortical mantle widths (FCMW) were determined for each patient. Four of 14 children demonstrated normal outcomes while 5 of 14 children showed abnormal outcomes. The remaining 5 children demonstrated minimally impaired outcomes. No child with a postoperative FCMW below 30 mm showed normal development on any scale, while all children with abnormal development demonstrated a postoperative FCMW of 21 mm or less. In conclusion, the prognosis for normal long-term neurodevelopment in infants with IAS, despite prompt ex utero treatment, is guarded; the majority of such children will show developmental delays of varying degreès. The FCMW serves as a reasonable prognostic indicator in this patient population. [ABSTRACT FROM AUTHOR]

The technique of protoplast fusion has been applied to the problem of unstable diploidy in the yeast Kluyveromyces lactis. By protoplast fusion between heterothallic strains of like mating-type, sporulation-deficient hybrids can be obtained. Biochemical, cytological, and genetical characterisation of these hybrids suggests that the majority of fusion products are diploid. Sporulating hybrids can be constructed by protoplast fusion between homothallic strains. Tetrad analysis of these hybrids demonstrates conclusively the diploid nature of fusion products. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the clinical robustness of a commercially developed data-driven respiratory gating algorithm based on principal component analysis, for use in routine PET imaging.Methods: One hundred fifty-seven adult FDG PET examinations comprising a total of 1149 acquired bed positions were used for the assessment. These data are representative of FDG scans currently performed at our institution. Data were acquired for 4 min/bed position (3 min/bed for legs). The data-driven gating (DDG) algorithm was applied to each bed position, including those where minimal respiratory motion was expected. The algorithm provided a signal-to-noise measure of respiratory-like frequencies within the data, denoted as R. Qualitative evaluation was performed by visual examination of the waveforms, with each waveform scored on a 3-point scale by two readers and then averaged (score S of 0 = no respiratory signal, 1 = some respiratory-like signal but indeterminate, 2 = acceptable signal considered to be respiratory). Images were reconstructed using quiescent period gating and compared with non-gated images reconstructed with a matched number of coincidences. If present, the SUVmax of a well-defined lesion in the thorax or abdomen was measured and compared between the two reconstructions.Results: There was a strong (r = 0.86) and significant correlation between R and scores S. Eighty-six percent of waveforms with R ≥ 15 were scored as acceptable for respiratory gating. On average, there were 1.2 bed positions per patient examination with R ≥ 15. Waveforms with high R and S were found to originate from bed positions corresponding to the thorax and abdomen: 90% of waveforms with R ≥ 15 had bed centres in the range 5.6 cm superior to 27 cm inferior from the dome of the liver. For regions where respiratory motion was expected to be minimal, R tended to be < 6 and S tended to be 0. The use of DDG significantly increased the SUVmax of focal lesions, by an average of 11% when considering lesions in bed positions with R ≥ 15.Conclusions: The majority of waveforms with high R corresponded to the part of the patient where respiratory motion was expected. The waveforms were deemed suitable for respiratory gating when assessed visually, and when used were found to increase SUVmax in focal lesions. [ABSTRACT FROM AUTHOR]

Apoptosis inhibitor of macrophage (AIM, encoded by cd5l) is a multi-functional circulating protein that has a beneficial role in the regulation of a broad range of diseases, some of which are ameliorated by AIM administration in mice. In blood, AIM is stabilized by association with IgM pentamers and maintains its high circulating levels. The mechanism regulating the excessive accumulation of blood AIM remains unknown, although it is important, since a constitutive increase in AIM levels promotes chronic inflammation. Here we found a physiological AIM-cleavage process that induces destabilization of AIM and its excretion in urine. In blood, IgM-free AIM appeared to be cleaved and reduced in size approximately 10 kDa. Cleaved AIM was unable to bind to IgM and was selectively filtered by the glomerulus, thereby excreted in urine. Amino acid substitution at the cleavage site resulted in no renal excretion of AIM. Interestingly, cleaved AIM retained a comparable potency with full-length AIM in facilitating the clearance of dead cell debris in injured kidney, which is a key response in the recovery of acute kidney injury. Identification of AIM-cleavage and resulting functional modification could be the basis for designing safe and efficient AIM therapy for various diseases. [ABSTRACT FROM AUTHOR]

The ever-increasing brightness of synchrotron radiation sources demands improved X-ray optics to utilise their capability for imaging and probing biological cells, nanodevices, and functional matter on the nanometer scale with chemical sensitivity. Here we demonstrate focusing a hard X-ray beam to an 8 nm focus using a volume zone plate (also referred to as a wedged multilayer Laue lens). This lens was constructed using a new deposition technique that enabled the independent control of the angle and thickness of diffracting layers to microradian and nanometer precision, respectively. This ensured that the Bragg condition is satisfied at each point along the lens, leading to a high numerical aperture that is limited only by its extent. We developed a phase-shifting interferometric method based on ptychography to characterise the lens focus. The precision of the fabrication and characterisation demonstrated here provides the path to efficient X-ray optics for imaging at 1 nm resolution. [ABSTRACT FROM AUTHOR]

A correction to the article “Analyses of allele-specific gene expression in highly divergent mouse crosses identifies pervasive allelic imbalance" that was published online on 2nd March, 2015 after print in the 16th April, 2015 issue is presented.

Multilayer Laue lenses are volume diffraction elements for the efficient focusing of X-rays. With a new manufacturing technique that we introduced, it is possible to fabricate lenses of sufficiently high numerical aperture (NA) to achieve focal spot sizes below 10 nm. The alternating layers of the materials that form the lens must span a broad range of thicknesses on the nanometer scale to achieve the necessary range of X-ray deflection angles required to achieve a high NA. This poses a challenge to both the accuracy of the deposition process and the control of the materials properties, which often vary with layer thickness. We introduced a new pair of materials-tungsten carbide and silicon carbide-to prepare layered structures with smooth and sharp interfaces and with no material phase transitions that hampered the manufacture of previous lenses. Using a pair of multilayer Laue lenses (MLLs) fabricated from this system, we achieved a two-dimensional focus of 8.4 × 6.8 nm 2 at a photon energy of 16.3 keV with high diffraction efficiency and demonstrated scanning-based imaging of samples with a resolution well below 10 nm. The high NA also allowed projection holographic imaging with strong phase contrast over a large range of magnifications. An error analysis indicates the possibility of achieving 1 nm focusing., Competing Interests: The authors declare no conflict of interest.