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Tagging salmon smolts to provide information about the timing of outmigration has been a common approach to monitor phenology and model the risk of encountering stressors. However, the validity of tagging has come under scrutiny because of the sensitivity of this parameter in various management systems. We studied the probability of migration, timing of migration and growth during migration for Atlantic salmon smolts tagged with three different tags in the River Dale, western Norway. Two groups were tagged with passive integrated transponder (PIT) tags via a small ventral nonsurgical incision, either a 12 mm or a new 16 mm PIT tag. Two groups were subjected to surgical implantation of either a dummy acoustic transmitter or a 12 mm PIT tag (a sham surgery). Overall, 71% of the tagged smolts were recaptured at the downstream Wolf trap. Smolts from the sham tagged group were recaptured most frequently (78%) compared to dummy acoustic transmitters and 16 mm PIT tags (both 68%), but the differences were not significant. Results agree with prior assessments that longer smolts migrated earlier, with about half a day earlier migration for each millimetre total length of the smolt, but did not suggest any difference in time of migration among the tag types. Growth in length was evident from release to recapture, with smaller smolts exhibiting greater growth and no effect of tagging treatment. Our findings suggest that inferences about the timing of outmigration for salmon smolts based on acoustic tagging should be made cautiously because of the relationship among tag size, suitable fish size and the timing of a tagged individual's migration. publishedVersion

International audience; Leaf optical properties impact leaf energy balance and thus leaf temperature. The effect of leaf development on mid-infrared (MIR) reflectance, and hence thermal emissivity, has not been investigated in detail. We measured a suite of morphological characteristics, as well as directional-hemispherical reflectance from ultraviolet to thermal infrared wavelengths (250 nm to 20 µm) of leaves from five temperate deciduous tree species over the 8 wk following spring leaf emergence. By contrast to reflectance at shorter wavelengths, the shape and magnitude of MIR reflectance spectra changed markedly with development. MIR spectral differences among species became more pronounced and unique as leaves matured. Comparison of reflectance spectra of intact vs dried and ground leaves points to cuticular developmentand not internal structural or biochemical changesas the main driving factor. Accompanying the observed spectral changes was a drop in thermal emissivity from about 0.99 to 0.95 over the 8 wk following leaf emergence. Emissivity changes were not large enough to substantially influence leaf temperature, but they could potentially lead to a bias in radiometrically measured temperatures of up to 3 K. Our results also pointed to the potential for using MIR spectroscopy to better understand species-level differences in cuticular development and composition.

Amplification of the MYCN oncogene occurs in approximately 25% of primary neuroblastomas and is the single most powerful biological marker of poor prognosis in this disease. MYCN transcriptionally regulates a range of biological processes important for cancer, including cell metabolism. The MYCN-regulated metabolic gene SLC16A1, encoding the lactate transporter monocarboxylate transporter 1 (MCT1), is a potential therapeutic target. Treatment of neuroblastoma cells with the MCT1 inhibitor SR13800 increased intracellular lactate levels, disrupted the nicotinamide adenine dinucleotide (NADH/NAD(+)) ratio and decreased intracellular glutathione levels. Metabolite tracing with 13C-glucose and 13C-glutamine following MCT1 inhibitor treatment revealed increased quantities of tricarboxylic acid (TCA) cycle intermediates and increased oxygen consumption rate. MCT1 inhibition was highly synergistic with vincristine under cell culture conditions, but this combination was ineffective against neuroblastoma xenografts in mice. Post-treatment xenograft tumors had increased expression of the MCT1 homolog MCT4/SLC16A, a known resistance factor to MCT1 inhibition. We found that MCT4 was negatively regulated by MYCN in luciferase reporter assays and its expression in neuroblastoma cells was increased under hypoxic conditions and following hypoxia-inducible factor (HIF1) induction, suggesting that MCT4 may contribute to resistance to MCT1 inhibitor treatment in hypoxic neuroblastoma tumors. Co-treatment of neuroblastoma cells with inhibitors of MCT1 and LDHA, the enzyme responsible for lactate production, resulted in a large increase in intracellular pyruvate and was highly synergistic in decreasing neuroblastoma cell viability. These results highlight the potential of targeting MCT1 in neuroblastoma in conjunction with strategies that involve disruption of pyruvate homeostasis and indicate possible resistance mechanisms.

Fused silica diffusers, made by forming scattering centers inside fused silica glass, can exhibit desirable optical properties, such as reflectance or transmittance independent of viewing angle, spectrally flat response into the ultraviolet wavelength range, and good spatial uniformity. The diffusers are of interest for terrestrial and space borne remote sensing instruments, which use light diffusers in reflective and transmissive applications. In this work, we report exploratory measurements of two samples of fused silica diffusers. We will present goniometric bidirectional scattering distribution function (BSDF) measurements under normal illumination provided by the National Institute of Standards and Technology (NIST)’s Goniometric Optical Scatter Instrument (GOSI), by NIST’s Infrared reference integrating sphere (IRIS) and by the National Aeronautics and Space Administration (NASA)’s Diffuser Calibration Laboratory. We also present hemispherical diffuse transmittance and reflectance measurements provided by NIST’s Double integrating sphere Optical Scattering Instrument (DOSI). The data from the DOSI is analyzed by Prahl’s inverse adding-doubling algorithm to obtain the absorption and reduced scattering coefficient of the samples. Implications of fused silica diffusers for remote sensing applications are discussed.

Due to the relatively high flux levels available in FT-IR spectrophotometers and the universal need for better signal to noise ratios, detectors are often operated in conditions under which their responsivity varies during the measurement. This can happen both during a single measurement (nonlinearity) as well as between measurements (nonequivalence). The results of measurements made under these conditions will contain errors. The quantity and spectral distribution of the errors will depend on both the instrument signature and the sample properties under investigation.

While FT-IR spectrophotometers have clear advantages over dispersive instruments in throughput and signal averaging, the same design elements that give these advantages can produce more complicated and severe sources of radiometric error in FTIR spectra compared to their dispersive counterparts. However, the high signal-to-noise ratio and good measurement repeatability afforded by FT-IR spectrophotometers are sometimes misinterpreted as low absolute radiometric uncertainty. While the complete radiometric characterization of even one FT-IR instrument is an ambitious long-term goal, it should be possible for users to both understand and reduce the various sources of radiometric error through the use of standard and diagnostic samples appropriate to the measurements of interest.

MRP1 (ABCC1) is a membrane transporter that confers multidrug resistance in cancer cells by exporting chemotherapeutic agents, often in a reduced glutathione (GSH)-dependent manner. This transport activity can be altered by compounds (modulators) that block drug transport while simultaneously stimulating GSH efflux by MRP1. In MRP1-expressing cells, modulator-stimulated GSH efflux can be sufficient to deplete GSH and increase sensitivity to chemotherapy, enhancing cancer cell death. Further development of clinically useful MRP1 modulators requires a better mechanistic understanding of modulator binding and its relationship to GSH binding and transport. Here, we explore the mechanism of two MRP1 small molecule modulators, 5681014 and 7914321, in relation to a bipartite substrate-binding cavity of MRP1. Binding of these modulators to MRP1 was dependent on the presence of GSH but not its reducing capacity. Accordingly, the modulators poorly inhibited organic anion transport by K332L-mutant MRP1, where GSH binding and transport is limited. However, the inhibitory activity of the modulators was also diminished by mutations that limit E

We describe an algorithm to extract the complex refractive index of a material from broadband reflectance and transmittance measurements taken by spectrophotometers. The algorithm combines Kramers–Kronig analysis with an inversion of Fresnel’s equations to provide a direct method of solving for the refractive index which is accurate, even for weakly absorbing materials, and easily applicable to radiative heat transfer calculations. The algorithm is validated by extracting the complex refractive index of polydimethylsiloxane between 0.25 μm and 100 μm and comparing against existing literature. We also discuss the importance of broadband optical properties to passive radiative cooling and details of the uncertainty analysis of the algorithm.

Members of the ABC transporter family, particularly P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP, ABCG2) and multidrug resistance protein 1 (MRP1, ABCC1) are well characterized mediators of multidrug resistance, however their pharmacological inhibition has so far failed as a clinical strategy. Harnessing collateral sensitivity, a form of synthetic lethality where cells with acquired multidrug resistance exhibit hypersensitivity to unrelated agents, may be an alternative approach to targeting multidrug resistant tumour cells. We characterized a novel small molecule modulator that selectively enhanced MRP1-dependent efflux of reduced glutathione (GSH), an endogenous MRP1 substrate. Using cell lines expressing high levels of endogenous MRP1 from three difficult to treat cancer types-lung cancer, ovarian cancer and high-risk neuroblastoma-we showed that the MRP1 modulator substantially lowered intracellular GSH levels as a single agent. The effect was on-target, as MRP1 knockdown abolished GSH depletion. The MRP1 modulator was synergistic with the GSH synthesis inhibitor buthionine sulfoximine (BSO), with the combination exhausting intracellular GSH, increasing intracellular reactive oxygen species (ROS) and abolishing clonogenic capacity. Clonogenicity was rescued by the ROS scavenger N-acetylcysteine, implicating GSH depletion in the effect. The MRP1 modulator in combination with BSO also strongly sensitized cancer cells to MRP1-substrate chemotherapeutic agents, particularly arsenic trioxide, and was more effective than either the MRP1 modulator or BSO alone. GSH-depleting MRP1 modulators may therefore provide an enhanced therapeutic window to treat chemo-resistant MRP1-overexpressing pediatric and adult cancers.

This paper describes advances in measuring the characteristic spatial distribution of surface temperature and emissivity during laser-metal interaction under conditions relevant for laser powder bed fusion (LPBF) additive manufacturing processes. Detailed descriptions of the measurement process, results, and approaches to determining uncertainties are provided. Measurement uncertainties have complex dependencies on multiple process parameters, so the methodology is demonstrated on one set of process parameters and one material. Well-established literature values for high-purity nickel solidification temperature and emissivity at the solidification temperature were used to evaluate the predicted uncertainty of the measurements. The standard temperature measurement uncertainty is found to be approximately 0.9 % of the absolute temperature (16 °C), and the standard relative emissivity measurement uncertainty is found to be approximately 8 % at the solidification point of high-purity nickel, both of which are satisfactory. This paper also outlines several potential sources of test uncertainties, which may require additional experimental evaluation. The largest of these are the metal vapor and ejecta that are produced as process by-products, which can potentially affect the imaging quality, reflectometry results, and thermal signature of the process, while also affecting the process of laser power delivery. Furthermore, the current paper focuses strictly on the uncertainties of the emissivity and temperature measurement approach and therefore does not detail a variety of uncertainties associated with experimental controls that must be evaluated for future generation of reference data.

Background With the emergence of coronary computed tomography (CT) angiography, anomalous aortic origin of a coronary artery (ANOCOR) is more frequently diagnosed. Fractional flow reserve derived from CT (FFRCT) is a noninvasive functional test providing anatomical and functional evaluation of the overall coronary tree. These unique features of anatomical and functional evaluation derived from CT could help for the management of patients with ANOCOR. We aimed to retrospectively evaluate the physiological and clinical impact of FFRCT analysis in the ANOCOR registry population. Methods and Results The ANOCOR registry included patients with ANOCOR detected during invasive coronary angiography or coronary CT angiography between January 2010 and January 2013, with a planned 5‐year follow‐up. We retrospectively performed FFRCT analysis in patients with coronary CT angiography of adequate quality. Follow‐up was performed with a clinical composite end point (cardiac death, myocardial infarction, and unplanned revascularization). We obtained successful FFRCT analyses and 5‐year clinical follow‐up in 54 patients (average age, 60±13 years). Thirty‐eight (70%) patients had conservative treatment, and 16 (30%) patients had coronary revascularization after coronary CT angiography. The presence of an ANOCOR course was associated with a moderate reduction of FFRCT value from 1.0 at the ostium to 0.90±0.10 downstream the ectopic course and 0.82±0.11 distally. No significant difference in FFRCT values was identified between at‐risk and not at‐risk ANOCOR. After a 5‐year follow‐up, only one unplanned percutaneous revascularization was reported. Conclusions The presence of ANOCOR was associated with a moderate hemodynamic decrease of FFRCT values and associated with a low risk of cardiovascular events after a 5‐year follow‐up in this middle‐aged population.

Smolt migration through lakes is hazardous, as the predation pressure can be extreme and the hydrology a great contrast to that of a riverine area. However, the mechanisms yielding these challenges have been scarcely investigated. We conducted an acoustic telemetry field study in Lake Evangervatnet, Voss, Norway, utilising Vemco V5 predation tags. Atlantic salmon (Salmo salar) smolts (N = 20) were tagged with the novel predation sensor tag to investigate mortality, the lacustrine migration behaviour of smolts, and the applicability of these tags for smolt studies. A total of 60% of tagged Atlantic salmon (Salmo salar) smolts perished in the lake. Half of the mortalities (30% of tagged fish) were directly attributed to predation by brown trout (Salmo trutta) based on predation sensors. The surviving smolts were slow to traverse the 6.5 km lake, with progression rate between lake inlet and outlet on average 0.016 m/s over a mean of 7.9 ± 6.2 (SD) days. Acoustic detections revealed a consistent pattern of nocturnal migration and multidirectional movements within the lake. By running a series of correlated random walks under varying parameters and comparing the simulated travel times to the observed travel time used by the tagged smolts, we emulated the observed behaviour of the smolts. These simulations suggested that smolts lacked the ability to efficiently navigate through the lake, instead swimming in random directions until they reached the lake outlet. Predation sensors can offer improved resolution when tracking the behaviour and fate of smolts and can facilitate better mitigation efforts by identifying survival bottlenecks and separating predation from non-predatory mortality. publishedVersion

Plant virus management strategies have largely been limited to the application of hygiene protocols, the control of viral vectors such as insects and nematodes and the use of resistant varieties. However, these approaches are often insufficient to prevent infections. The rapid control of newly emerging viral diseases remains challenging. This chapter focuses on cross-protection using mild viruses as active substances in biocontrol. The chapter begins by describing the theoretical modes of action of cross-protection. It then goes on to discuss crucial elements in the development of a cross-protection strategy, taking into account new insights based on commercial application of cross-protection. The chapter also provides case studies in which cross-protection has been applied in commercial crops, in particular vaccination strategies to control Pepino mosaic virus (PepMV) in greenhouse tomato. Finally, developments that may impact future research into the control of emerging viral pathogens are discussed.

Atlantic salmon is often a focal species of restoration efforts throughout the north Atlantic and it is therefore an excellent case study for how best to design programmes to address and mitigate threats and correct population declines. This perspective is written to promote the work that has been accomplished towards restoration of Atlantic salmon populations and synthesize how we believe the lessons can be used effectively to support efforts by management agencies to restore populations. We reviewed where restoration is needed for Atlantic salmon, agreed on definitions for three levels of successful restoration, and then applied these criteria to  published papers focused on Atlantic salmon restoration. We identified  successful examples of restoration among  papers reviewed and discussed what interventions led to success versus failure. We then addressed key questions about when hatchery stocking should be used as part of a restoration measure and whether local restoration efforts are enough when these wide-ranging species encounter broad-scale changes in the north Atlantic, specifically related to issues of climate change and to marine survival. We advise to avoid restoration as much as possible by protecting and managing existing populations and when restoration is necessary, problems should be identified and addressed in partnership with river users. With appropriate resources and research to resolve ongoing mysteries, restoration of lost Atlantic salmon populations is absolutely feasible. Keywords: ecosystem services, remediation, restoration, salmonidae, success.

Telemetry tags are increasingly used in management to monitor the migration timing of Atlantic salmon smolts (Salmo salar L.). It has been postulated that (1) effects from tagging and handling may alter migration behaviour, and (2) that the selection of fish during sampling is not representative of all migrating smolts, yielding bias in migration timing estimates. In the River Dale (Vestland, Norway), five groups of wild Atlantic salmon smolts (N = 385) were tagged in April–May and recaptured in a wolf trap. Migration timing was then compared to the untagged population. Migration timing differed between tagged (12 mm PIT) and untagged fish for 4/5 groups. Only fish tagged at the first time point did not have significantly different timing of migration from untagged counterparts. The relationship between length and the timing of migration was different for initial length and length at recapture; initial length suggested earlier migration of longer fish, but the extra time spent in the river prior to migrating for smolts that were initially smaller compensated for the size difference. The tagging protocol is crucial to obtaining representative migration timing results. Smolts should be tagged as early as possible and include the entire size distribution. publishedVersion

Despite the preponderance of exorheic lakes in rivers home to anadromous salmonids, little research has focused on how salmon, trout, and char use lakes as part of their anadromous life histories. The literature on this subject has so far revealed that some parr move into lakes to feed and grow before smoltification but that smolts moving through lakes tend to have high mortality in disproportion to what is observed in other habitats they migrate in or through. Adults have been observed using lakes for behavioural thermoregulation prior to spawning, and kelts of iteroparous species often exploit lakes to overwinter before returning to sea to recondition. We summarized knowledge on lakes as salmonid habitat and identified knowledge gaps about the use of lakes by anadromous salmonids related to whether lakes are barriers that structure genetics of populations, whether mortality in lakes is compensatory or additive, and whether systems with lakes have higher rates of repeat spawning among iteroparous salmonids. Human activities that alter lakes require further study to understand how changes in temperature, oxygen, ice, or circulation affect navigation and fate.

We describe an algorithm to extract the complex refractive index of a material from reflectance and transmittance measurements commonly taken by spectrophotometers. The algorithm combines Kramers-Kronig analysis with an inversion of Fresnel's equations to provide a direct method of solving for the refractive index which is accurate, even for weakly absorbing materials. We discuss the details of the uncertainty analysis of the algorithm. The algorithm is validated by extracting the complex refractive index of polydimethylsiloxane between 2 μm and 18 μm and comparing against existing literature.

Additive manufacturing involving layer-wise selective laser melting of a powder material, or laser powder bed fusion (LPBF), is a fast-growing industry. At the Additive Manufacturing Metrology Testbed (AMMT) at the United States National Institute of Standards and Technology (NIST) an integrating hemispherical reflectometer has recently been developed to facilitate measurements of spatially resolved reflectance of the laser-melting heat affected zone (HAZ) during the LPBF process. Reflectance is then used to determine spatially resolved emissivity. The design features of the hemispherical-directional reflectometer are discussed. Then, the reflectometer performance and measurement uncertainties are detailed. A two-dimensional map of emissivity and emissivity uncertainty of the HAZ around a meltpool of high-purity nickel are presented. It is found that emissivity measurements are in good agreement with literature values at the melting point of high-purity nickel with acceptable uncertainty.

The report identifies knowledge gaps on analysing climate change risks relating to the use of the impact chain framework, user-interface and stakeholder involvement, socio-economic scenarios and societal exposure to climate change and transboundary climate change impacts. The identified knowledge gaps are reformulated into several research questions to be addressed in the succeeding case-studies of the UNCHAIN project.

Background: Previous studies found evidence that dispositional optimism is related to lower pain sensitivity. Recent findings suggest that temporarily increasing optimism by means of imagining a positive future may also have pain‐alleviating effects.Objectives: The present experiment was designed to investigate conditioned pain modulation (CPM) as a potential underlying mechanism of this pain‐alleviating effect of induced optimism.Methods: For this purpose, 45 healthy participants were randomized into an optimistic or neutral imagery condition. Additionally, participants completed questionnaires on dispositional optimism, pain catastrophizing and pain expectations. CPM was assessed by delivering a series of five heat pain stimuli on the nondominant hand before and during immersion of the dominant hand in water of 5°C for 70 s.Results: A clear CPM effect was found, that is heat pain reports were lower during simultaneous cold water stimulation. Although the optimism manipulation successfully increased optimism, it did not affect pain ratings or CPM. Post hoc analyses indicated that dispositional optimism was not associated with the magnitude of CPM, but pain catastrophizing and pain expectations did significantly correlate with the CPM effect.Conclusion: Pain‐specific but not general cognitions appear to influence endogenous pain modulation.Significance: Conditioned pain modulation is not the underlying mechanism of the pain‐alleviating effects of induced optimism. However, pain‐specific cognitions including pain catastrophizing and pain expectations affect endogenous pain modulation which should be taken into account in treatment and CPM research.

The standard uncertainty of detector-based radiance and irradiance responsivity calibrations in the short-wave infrared (SWIR) traditionally has been limited to around 1% or higher by the poor spatial uniformity of detectors used to transfer the scale from radiant power. Pyroelectric detectors offer a solution that avoids the spatial uniformity uncertainty but also introduces additional complications due to alternating current (AC) measurement techniques. Herein, a new, to the best of our knowledge, method for low uncertainty irradiance responsivity calibrations in the SWIR is presented. An absolute spectral irradiance responsivity scale was placed on two pyroelectric detectors (PED) at wavelengths λ from 500 to 3400 nm. The total combined uncertainty ( k = 1 ) was ≈ 0.28 % ( > 1000 nm ), 0.44% (900 nm), and 0.36% ( ≈ 950 nm and < 900 nm ) for PED #1 and 0.34% ( > 1000 nm ), 0.48% (900 nm), and 0.42% ( ≈ 950 nm and < 900 nm ) for PED #2. This was done by utilizing a demodulation technique to digitally analyze the time-dependent AC waveforms, which obviates the use of lock-in amplifiers and avoids associated additional uncertainty components.

Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Amplification of the MYCN oncogene is associated with an aggressive phenotype and poor outcome in childhood neuroblastoma. Polyamines are highly regulated essential cations that are frequently elevated in cancer cells, and the rate-limiting enzyme in polyamine synthesis, ornithine decarboxylase 1 (ODC1), is a direct transcriptional target of MYCN. Treatment of neuroblastoma cells with the ODC1 inhibitor difluoromethylornithine (DFMO), although a promising therapeutic strategy, is only partially effective at impeding neuroblastoma cell growth due to activation of compensatory mechanisms resulting in increased polyamine uptake from the surrounding microenvironment. In this study, we identified solute carrier family 3 member 2 (SLC3A2) as the key transporter involved in polyamine uptake in neuroblastoma. Knockdown of SLC3A2 in neuroblastoma cells reduced the uptake of the radiolabeled polyamine spermidine, and DFMO treatment increased SLC3A2 protein. In addition, MYCN directly increased polyamine synthesis and promoted neuroblastoma cell proliferation by regulating SLC3A2 and other regulatory components of the polyamine pathway. Inhibiting polyamine uptake with the small-molecule drug AMXT 1501, in combination with DFMO, prevented or delayed tumor development in neuroblastoma-prone mice and extended survival in rodent models of established tumors. Our findings suggest that combining AMXT 1501 and DFMO with standard chemotherapy might be an effective strategy for treating neuroblastoma.

Introduction Polyneuropathy (PN) is a common condition with significant morbidity. We developed tele-polyneuropathy (tele-PN) clinics to improve access to neurology and increase guideline-concordant PN care. This article describes the mixed-methods evaluation of pilot tele-PN clinics at three community sites within the Greater Los Angeles VA Healthcare System. Methods For the first 25 patients (48 scheduled visits), we recorded the duration of the tele-PN visit and exam; the performance on three guideline-concordant care indicators (PN screening labs, opiate reduction, physical therapy for falls); and patient-satisfaction scores. We elicited comments about the tele-PN clinic from patients and the clinical team. We combined descriptive statistics with qualitative themes to determine the feasibility and acceptability of the tele-PN clinics. Results The average tele-PN encounter and exam times were 28.5 and 9.1 min, respectively. PN screening lab completion increased from 80 to 100%. Opiate freedom improved from 68 to 88%. Physical therapy for patients with recent falls increased from 58 to 100%. The tele-PN clinic was preferred for follow-up over in-person clinics in 86% of cases. Convenience was paramount to the clinic’s success, saving an average of 231 min per patient in round-trip travel. The medical team’s caring and collaborative spirit received high praise. While the clinic’s efficiency was equal or superior to in-person care, the limited treatment options for PN and the small clinical exam space are areas for improvement. Conclusion In this pilot, we were able to efficiently see and examine patients remotely, promote guideline-concordant PN care, and provide a high-satisfaction encounter.

Pepino mosaic virus (PepMV) has emerged as an important pathogen of greenhouse tomato crops and is currently distributed worldwide. Population genetic studies have revealed a shift in the dominant PepMV genotype from European (EU) to Chilean 2 (CH2) in North America and several European countries. New genetic variants are constantly being created by mutation and recombination events. Single nucleotide substitutions in different parts of the genome were found to affect on development of symptoms resulting in new pathotypes and accumulation of viral RNA. The variability of the PepMV population has a great impact on designing specific diagnostic tools and developing efficient and durable strategies of disease control. In this paper we review the current knowledge about the PepMV population, the evolutionary dynamics of this highly infective virus, methods for its detection and plant protection strategies.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder associated with dysfunction of movement, memory, and the peripheral nervous system. We report an 82 years old male who presented with tremors and difficulty with balance that started at 65 years of age. His motor examination revealed decreased strength in left lower extremity. Tremors were seen in both the upper limbs at rest that worsened with movement. Bilateral lower extremities showed absent vibration and proprioception sensations, absent reflexes and upgoing toes. Electrodiagnostic studies revealed sensory predominant axonal sensory-motor peripheral polyneuropathy. Brain MRI revealed microvascular ischemic changes. The cervical and lumbar MRI showed diffuse degenerative changes. Genetic test for heritable causes of ataxia revealed a premutation in Fragile X gene (84 CGG repeats), confirming the diagnosis of FXTAS. On further genetic testing three out of his four daughters also tested positive for the FMR1 premutation. In appropriate clinical setting, Fragile X-associated tremor/ataxia syndrome (FXTAS) should be considered in every middle aged/elderly patient who presented with slowly progressive ataxia, tremor and peripheral polyneuropathy without any history of cognitive or neurological disabilities in childhood.

Background The zoophytophagous predator Macrolophus pygmaeus Rambur (Hemiptera: Miridae) is a successful biocontrol agent against several pest species in protected tomato crops. This predator is considered to be harmless for the crop. However, in recent years, Heteroptera feeding punctures on tomato fruit in Belgian and Dutch greenhouses have been misinterpreted as Pepino mosaic virus (PepMV) symptoms. In this study, three hypotheses were tested: (1) M. pygmaeus causes fruit damage that increases with population density and surpasses economic thresholds; (2) the presence of prey or alternative prey reduces the damage; (3) an infection of the tomato plants by PepMV triggers or aggravates M. pygmaeus fruit damage. Results At increasing M. pygmaeus densities, the severity of fruit damage increased from a few dimples towards yellowish discoloration and deformed fruits. A correlation with an infection with PepMV was found. The severity of the symptoms was independent of the presence of prey. A minimum economic density threshold was estimated at 0.32 M. pygmaeus per leaf. Conclusion M. pygmaeus can cause economic damage to tomato fruits at densities common in practice. An infection of the plants with PepMV enhances fruit symptoms significantly. Interacting plant defence responses are most likely the key to explaining this, although confirmation is required. © 2015 Society of Chemical Industry.

We have developed methods to measure the directional-hemispherical (ρ) and diffuse (ρd) reflectances of powders, liquids, and disks of powders and solid materials using a commercially available, matte gold-coated integrating sphere and Fourier transform infrared spectrometer. To determine how well the sphere and protocols produce quantitative reflectance data, measurements were made of three diffuse and two specular standards prepared by the National Institute of Standards and Technology (NIST), LabSphere Infragold and Spectralon standards, hand-loaded sulfur and talc powder samples, and water. Relative to the NIST measurements of the NIST standards, our directional hemispherical reflectance values are within ±4% for four of the standards and within ±7% for a low reflectance diffuse standard. For the three diffuse reflectance NIST standards, our diffuse reflectance values are within ±5% of the NIST values. For the two specular NIST standards, our diffuse reflectance values are an order of magnitude larger than those of NIST, pointing to a systematic error in the manner in which diffuse reflectance measurements are made for specular samples using our methods and sphere. Sources of uncertainty are discussed in the paper.

Purpose of review. Pain is an intense experience that can place a heavy burden on peoples’ lives. The identification of psychosocial risk factors led to the development of effective pain treatments. However, effect sizes are modest. Accumulating evidence suggests that enhancing protective factors might also contribute to (well-being despite) pain. Recent findings on positive affect (interventions) towards pain-related outcomes will be reviewed and new avenues for treatment of persistent pain will be discussed. Recent findings. Positive affect significantly attenuates the experience of pain in healthy and clinical populations. Positive affect interventions effectively reduce pain sensitivity and bolster well-being despite pain. Through both psychological and (neuro-)biological pathways, but also through its effect on central treatment processes such as inhibitory learning, positive affect can optimize the efficacy of existing treatments. Summary. Comprehensive understanding of the unique roles and dynamic interplay of positive and negative affect in moderating pain may optimize the treatment of (persistent) pain. ispartof: Current Rheumatology Reports vol:19 issue:12 ispartof: location:United States status: published

Pyroelectric radiometers with spectrally constant response have been developed at NIST with the cooperation of a few detector manufacturers. The new devices have noise-equivalent-power (NEP) values less than 1 nW/Hz1/2 sufficiently low for use at the output of regular monochromators. Their response flatness is an order of magnitude better than that of filtered Si detectors and can be used to realize simple and low-uncertainty responsivity scales for the UV and IR wavelength ranges. For the first time, the UV irradiance responsivity of a pyroelectric detector has been determined. Based on spectral reflectance measurements of the black coating of the pyroelectric detector, the relative spectral response was determined between 0.25 μm and 30 μm. The relative response was then converted into spectral power and irradiance responsivities using absolute tie points from a silicon-trap-detector in the VIS range. In addition to the UV irradiance responsivity scale realization, the flat response between 1.6 μm and 2.6 μm was utilized and a constant irradiance responsivity was realized and applied as a reference scale for the Spectral Irradiance and Radiance Responsivity Calibrations with Uniform Sources (SIRCUS) facility of NIST. The spectral power responsivity of the low-NEP pyroelectric detector is the internal standard of the NIST VIS-IR detector calibration facility for the 0.6 μm to 24 μm wavelength range. The pyroelectric standard is used to calibrate other types of detectors for spectral responsivity using detector substitution. The flat-response interval of the pyroelectric standard, calibrated for irradiance responsivity, was also used to measure the integrated irradiance from UV LED sources without using any source standard. The broadband radiometric measurements can be applied to IR LEDs emitting low fluxes between 750 nm and 4300 nm. All pyroelectric detector based calibrations were performed with expanded uncertainties of about 2 % (k=2).

The ATP-binding cassette transporter ABCC4 (multidrug resistance protein 4, MRP4) mRNA level is a strong predictor of poor clinical outcome in neuroblastoma which may relate to its export of endogenous signalling molecules and chemotherapeutic agents. We sought to determine whether ABCC4 contributes to development, growth and drug response in neuroblastoma in vivo. In neuroblastoma patients, high ABCC4 protein levels were associated with reduced overall survival. Inducible knockdown of ABCC4 strongly inhibited the growth of human neuroblastoma cells in vitro and impaired the growth of neuroblastoma xenografts. Loss of Abcc4 in the Th-MYCN transgenic neuroblastoma mouse model did not impact tumour formation; however, Abcc4-null neuroblastomas were strongly sensitised to the ABCC4 substrate drug irinotecan. Our findings demonstrate a role for ABCC4 in neuroblastoma cell proliferation and chemoresistance and provide rationale for a strategy where inhibition of ABCC4 should both attenuate the growth of neuroblastoma and sensitise tumours to ABCC4 chemotherapeutic substrates.

Multidrug resistance protein 1 (MRP1) is an ATP-dependent efflux pump that extrudes chemotherapeutic drugs from cancer cells, preventing their intracellular accumulation and thus their efficacy. MRP1 also regulates intracellular levels of glutathione (GSH), an antioxidant that when elevated in cancer provides resistance against chemotherapy- and radiotherapy-induced oxidative damage. The different binding sites for drugs and GSH on MRP1 has allowed the development of small molecule MRP1 modulators that block chemotherapy efflux whilst simultaneously enhancing GSH efflux to deplete GSH. As no therapeutic options are available to combat MRP1-mediated multidrug resistance, we have been investigating MRP1 modulators for their efficacy in sensitizing MRP1-expressing cancers to treatment. MRP1 immunohistochemistry staining in ovarian and non-small cell lung cancer (NSCLC) patient samples was assessed to determine the frequency of high MRP1 expression. High MRP1 staining was frequently observed in the subcellular compartment (37%, 47%) and, to a lesser extent, plasma membrane (7%, 16%) in ovarian and NSCLC patient tumour samples respectively. In NSCLC, subcellular MRP1 was associated with poorer overall survival in late stage disease (p=0.0095) and membrane MRP1 with poorer disease-free survival in Stage 4 cancer (p=0.01449). Analysis for ovarian cancer is ongoing. As MRP1 is therefore an attractive target for inhibition, we used membrane vesicle uptake assays to compare the ability of modulators to inhibit [3H]-labelled MRP1 substrate transport. 7-(difluoromethyl)-N-4-morpholinyl-5-phenylpyrazolo[1,5-a]pyrimidine-3-carboxamide (7914321) was identified as an analogue of the MRP1 inhibitor Reversan with improved potency. Interestingly, this inhibition was GSH dependent. Exploring further this relationship with GSH, the high MRP1-expressing A549 lung and SKOV3 ovarian cancer cell lines were treated with 7914321 alone or in combination with the GSH synthesis inhibitor buthionine sulfoximine (BSO), then GSH levels were determined by glutathione recycling assay. 7914321 stimulated GSH efflux in both cell lines in an MRP1-dependent manner and strongly synergised with BSO to cause near complete GSH depletion. To determine the potential of this synergistic GSH depletion to chemosensitize cells, the viability of A549 and SKOV3 cells treated with chemotherapy, 7914321, and BSO was assessed by clonogenic and resazurin-based cytotoxicity assays. 7914321/BSO significantly diminished clonogenicity in high but not low MRP1-expressing cells, and further sensitized cancer cell lines to MRP1-substrate chemotherapeutics compared to the single agents. Together, these findings provide preliminary evidence that 7914321 is a potent MRP1 modulator whose dual effects on MRP1 place it in a unique position to potentially enhance the therapeutic window to treat chemoresistant MRP1-overexpressing cancers. Citation Format: Kimberley M. Hanssen, Christine C. Gana, Madeleine S. Wheatley, Denise M. Yu, Claudia L. Flemming, Richard Young, Gavin M. Wright, Gwenaelle Conseil, Catherine J. Kennedy, Anna deFazio, Ben Solomon, Susan P. Cole, Murray D. Norris, Michelle Haber, Jamie I. Fletcher. Modulation of MRP1 activity reverses chemotherapy resistance in adult cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3809.

Recently, Pepino mosaic virus (PepMV) infections causing severe yellowing symptoms in tomato plants have been reported in glasshouse tomato crops. When studying this phenomenon in commercial glasshouses, two different types of yellowing symptoms, occurring in adjacent plants, were distinguished: interveinal leaf yellowing and yellow mosaics. After several weeks, the interveinal leaf yellowing symptoms gradually disappeared and the plant heads became green again, with yellow mosaic patterns on the leaves as an intermediate stage. The sequencing of multiple isolates causing interveinal leaf yellowing identified two point mutations, occurring in positions 155 and 166 of the coat protein (CP), as unique to the yellowing pathotype. Site-directed mutagenesis of infectious clones confirmed that both CP mutations are determinants of the interveinal leaf yellowing symptoms. Sequencing of CP clones from plants or plant parts with the yellow mosaic symptoms resulted in a mixture of wild-type and mutated sequences, whereas sequencing of CP clones from the green heads of recovered plants resulted in only wild-type sequences. Yellow mosaic symptoms could be reproduced by inoculation of an artificial 1:1 mixture of RNA transcripts from the wild-type and mutated infectious clones. These results show that the ratio of mutated versus wild-type sequences can determine the nature and severity of symptom development. The gradual recovery of the plants, which coincides with the disappearance of the yellowing mutations, suggests that selection pressure acts to the advantage of the wild-type virus. Experiments with wild-type and mutated infectious clones showed that reverse mutation events from mutant to wild-type occur and that the wild-type virus does not have a replicative advantage over the mutant. These results suggest that reverse mutation events occur, with subsequent selection pressure acting in favour of the wild-type virus in the growing plant parts, possibly related to a lower long-distance movement efficiency of the mutant.

The present study compared the effects of a one week best possible self intervention and a one week gratitude intervention on life satisfaction and optimism. We hypothesized that both interventions would lead to similar increases in life satisfaction, but that only the best possible self intervention would increase optimism. The results partly confirmed the hypotheses: only the best possible self intervention led to increased optimism immediately after the intervention period, which further increased one week after completion of the intervention. However, the best possible self intervention was also more effective in increasing life satisfaction than the gratitude intervention. Whereas the increase in life satisfaction in the best possible self intervention was significantly different from the control intervention, this was not the case in the gratitude condition. We conclude that the best possible self intervention is an effective exercise if one aims to increase optimism.

Previous studies have demonstrated a relation between dispositional optimism and lower pain sensitivity, but the causal status of this link remains unclear. This study sought to test the causal status by experimentally inducing a temporary optimistic state by means of writing about and visualizing a future best possible self. In addition, we explored pain expectations and (situational) pain catastrophizing as possible underlying mechanisms of the link between optimism and pain. Seventy-nine university students participated in a cold pressor task (CPT). Before the CPT, half of them received the optimism manipulation and the other half a control manipulation. Induced optimism was related to lower pain intensity ratings during the CPT compared to the control group, thereby experimentally confirming causality. This effect was not explained by pain-related expectations about the task. Situational pain catastrophizing, however, did seem to mediate the relation between optimism and pain. This study is novel in that it confirms the causal status of optimism towards pain. Additionally, the results reveal that positive interventions might provide a useful alternative in reducing pain catastrophizing as an extremely relevant target in pain treatment. (C) 2012 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.

At present, broadband radiometric measurements of LEDs with uniform and low-uncertainty results are not available. Currently, either complicated and expensive spectral radiometric measurements or broadband photometric LED measurements are used. The broadband photometric measurements are based on the CIE standardized V(λ) function, which cannot be used in the UV range and leads to large errors when blue or red LEDs are measured in its wings, where the realization is always poor. Reference irradiance meters with spectrally constant response and high-intensity LED irradiance sources were developed here to implement the previously suggested broadband radiometric LED measurement procedure [1, 2]. Using a detector with spectrally constant response, the broadband radiometric quantities of any LEDs or LED groups can be simply measured with low uncertainty without using any source standard. The spectral flatness of filtered-Si detectors and low-noise pyroelectric radiometers are compared. Examples are given for integrated irradiance measurement of UV and blue LED sources using the here introduced reference (standard) pyroelectric irradiance meters. For validation, the broadband measured integrated irradiance of several LED-365 sources were compared with the spectrally determined integrated irradiance derived from an FEL spectral irradiance lamp-standard. Integrated responsivity transfer from the reference irradiance meter to transfer standard and field UV irradiance meters is discussed.

We report the upgraded performance of the National Institute of Standards and Technology (NIST) facility for spectral responsivity calibrations of infrared (IR) detectors in both radiant power and irradiance measurement modes. The extension of the wavelength range of the previous scale, below 0.8 μm and above 19 μm in radiant power mode as well as above 5.3 μm in irradiance mode, became available as a result of multiple improvements. The calibration facility was optimized for low-level radiant flux. A significantly reduced noise-equivalent-power and a relatively constant spectral response were achieved recently on newly developed pyroelectric detectors. Also, an efficient optical geometry was developed for calibration of the spectral irradiance responsivity without using an integrating sphere. Simultaneously, the upgrade and maintenance of the NIST transfer standards, with an extended spectral range, were supported by spectral reflectance measurements of a transfer standard pyroelectric detector using a custom integrating sphere and a Fourier transform spectrometer. The sphere reflectance measurements performed in a relative mode were compared to a bare gold-coated mirror reference, separately calibrated at the Fourier transform Infrared Spectrophotometry facility to 18 μm. Currently, the reflectance data for the pyroelectric standard, available in the range up to 30 μm, are supporting the absolute power responsivity scale by the propagation of the reflectance curve to the absolute tie-spectrum in the overlapping range. Typical examples of working standard pyroelectric-, Si-, MCT-, InSb- and InGaAs- detectors are presented and their optimal use for scale dissemination is analyzed.

The National Institute of Standards and Technology's (NIST) Physical Measurement and Engineering Laboratories are jointly developing the Additive Manufacturing Measurement Testbed (AMMT)/ Temperature and Emittance of Melts, Powders and Solids (TEMPS) facilities. These facilities will be co-located on an open architecture laser-based powder bed fusion system allowing users full access to the system's operation parameters. This will provide users with access to machine-independent monitoring and control of the powder bed fusion process. In this paper there will be emphasis on the AMMT, which incorporates in-line visible light collection optics for monitoring and feedback control of the powder bed fusion process. We shall present an overview of the AMMT/TEMPS program and its goals. The optical and mechanical design of the open architecture powder-bed fusion system and the AMMT will also be described. In addition, preliminary measurement results from the system along with the current status of the system will be described.

Resume Objectifs Le coroscanner et la scintigraphie de perfusion myocardique (SPM) ont une tres bonne valeur predictive negative pour la detection de la maladie coronaire, mais une valeur predictive positive sous-optimale, menant a des coronarographies trop frequemment negatives surtout en cas d’epreuve equivoque. La combinaison des deux tests pourrait pallier leurs insuffisances et eviter l’exploration invasive. Patients et methodes Soixante-sept patients, a risque essentiellement intermediaire de maladie coronaire, ont beneficie du coroscanner (45 patients) ou de la scintigraphie myocardique (22 patients) en premiere ligne, suivi du second examen du fait d’un resultat equivoque du premier examen. Un defaut non concordant entre les deux tests etait considere faussement positif, a priori excluant la maladie coronaire, alors qu’un defaut concordant a priori confirmait la maladie. Tous les patients avec defauts concordants ont beneficie d’une coronarographie. Les patients avec defauts non concordants ont ete soumis a un suivi de 730 ± 377 jours (sept patients ont malgre tout beneficie d’une coronarographie). Resultats Des defauts non concordants ont ete trouves chez 41 patients, dont 7/7 avaient une coronarographie normale et 34/34 n’ont presente aucun evenement cardiaque majeur pendant le suivi. Des defauts concordants ont ete trouves chez 26 patients, dont la coronarographie s’est revelee positive dans 14 cas, suivie de revascularisation dans neuf cas. Conclusion Une strategie combinee coroscan-SPM pourrait dans certains cas permettre de reduire le recours a la coronarographie chez des patients ayant un resultat equivoque a l’un des tests.

We have measured the polarization-resolved bidirectional reflectance distribution function (BRDF) for two types of graphite used in the fabrication of high-temperature fixed point blackbody cavities in and out of the plane of incidence. Measurements were made at room temperature using 405 nm and 658 nm laser sources, and the samples were illuminated at angles of incidence varying from normal incidence to 70°. All of the samples exhibited non-Lambertian behaviour, including enhanced forward scatter at high incident angles, especially for s-polarized incident light. The directional-hemispherical reflectance for unpolarized incident light, obtained by integrating the BRDF measured at individual points in a hemisphere over the sample, ranged from 0.083 to 0.101, depending upon sample and incident angle. The potential impact of these measurements on emissivity models for graphite blackbody radiators and radiance temperature scale dissemination is discussed.