Showing papers by "Duquesne University published in 2013"
TL;DR: The authors showed that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages.
Abstract: Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (γ-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation.
2,504 citations
TL;DR: There is a need to summarize the current literature on phase II genes in the central nervous system (CNS) to help guide future studies on phase I, II and III genes as therapeutic targets in neurological diseases.
465 citations
TL;DR: The member check has been heralded as an important component of validation in qualitative research and has been used in order to assess the accuracy with which a researcher has represented a participant's subjectivity as discussed by the authors.
Abstract: The member check has been heralded as an important component of validation in qualitative research. Traditionally, the member check has been used in order to assess the accuracy with which a researcher has represented a participant’s subjectivity. Some theorists, however, have argued that change, rather than representation, should be sought as a primary goal for qualitative research. The difference between using representation or change as a marker of validity has been described as a transactional/transformation divide. I argue that the member check can be utilised to span this divide in order to support a holistic view of validity. In particular, I assert that researchers should not expect participant subjectivities to remain static throughout the research process. Examples of the member check used in this manner are provided.
401 citations
TL;DR: It is found that microglia/macrophages respond dynamically to TBI, experiencing a transient M2 phenotype followed by a shift to the M1 phenotype, which may propel WMI progression and represents a rational target for TBI treatment.
Abstract: Mononuclear phagocytes are a population of multi-phenotypic cells and have dual roles in brain destruction/reconstruction. The phenotype-specific roles of microglia/macrophages in traumatic brain injury (TBI) are, however, poorly characterized. In the present study, TBI was induced in mice by a controlled cortical impact (CCI) and animals were killed at 1 to 14 days post injury. Real-time polymerase chain reaction (RT–PCR) and immunofluorescence staining for M1 and M2 markers were performed to characterize phenotypic changes of microglia/macrophages in both gray and white matter. We found that the number of M1-like phagocytes increased in cortex, striatum and corpus callosum (CC) during the first week and remained elevated until at least 14 days after TBI. In contrast, M2-like microglia/macrophages peaked at 5 days, but decreased rapidly thereafter. Notably, the severity of white matter injury (WMI), manifested by immunohistochemical staining for neurofilament SMI-32, was strongly correlated with the number of M1-like phagocytes. In vitro experiments using a conditioned medium transfer system confirmed that M1 microglia-conditioned media exacerbated oxygen glucose deprivation–induced oligodendrocyte death. Our results indicate that microglia/macrophages respond dynamically to TBI, experiencing a transient M2 phenotype followed by a shift to the M1 phenotype. The M1 phenotypic shift may propel WMI progression and represents a rational target for TBI treatment.
374 citations
TL;DR: The purpose of these clinical practice guidelines is to describe the peer-reviewed literature and make recommendations related to ankle ligament sprain.
Abstract: The Orthopaedic Section of the American Physical Therapy Association (APTA) has an ongoing effort to create evidence-based practice guidelines for orthopaedic physical therapy management of patients with musculoskeletal impairments described in the World Health Organization's International Classification of Functioning, Disability, and Health (ICF). The purpose of these clinical practice guidelines is to describe the peer-reviewed literature and make recommendations related to ankle ligament sprain. J Orthop Sports Phys Ther 2013;43(9):A1–A40. doi:10.2519/jospt.2013.0305
211 citations
TL;DR: Overall, this review suggests that during gait activities with an added cognitive task, people with stroke are likely to demonstrate significant decrements in motor performance only (cognitive-related motor interference), or decrement in both motor and cognitive performance (mutual interference).
192 citations
01 Jan 2013
TL;DR: The author identification task at PAN-2014 focuses on author verification and adopts the c@1 measure, originally proposed for the question answering task, and continues the successful practice of the PAN labs to examine meta-models based on the combination of all submitted systems.
Abstract: The author identification task at PAN-2013 focuses on author verification where given a set of documents by a single author and a questioned document, the problem is to determine if the questioned document was written by that particular author or not. In this paper we present the evaluation setup, the performance measures, the new corpus we built for this task covering three languages and the evaluation results of the 18 participant teams that submitted their software. Moreover, we survey the characteristics of the submitted approaches and show that a very effective meta-model can be formed based on the output of the participant methods.
174 citations
Book•
23 Dec 2013TL;DR: In this article, the morphological, neural and cognitive foundations of primate communication through discussion of cutting-edge research are explored through a unified multimodal approach, considering signals from multiple modalities, and discussing what we know, what we don't know and what we may currently misunderstand about communication across different forms.
Abstract: Primates communicate with each other using a wide range of signals: olfactory signals to mark territories, screams to recruit help while fighting, gestures to request food and facial expressions to initiate play Primate Communication brings together research on all forms of interchange and discusses what we know about primate communication via vocal, gestural, facial, olfactory and integrated multimodal signals in relation to a number of central topics It explores the morphological, neural and cognitive foundations of primate communication through discussion of cutting-edge research By considering signals from multiple modalities and taking a unified multimodal approach, the authors offer a uniquely holistic overview of primate communication, discussing what we know, what we don't know and what we may currently misunderstand about communication across these different forms It is essential reading for researchers interested in primate behaviour, communication and cognition, as well as students of primatology, psychology, anthropology and cognitive sciences
157 citations
TL;DR: In this article, the authors explore and assess the use of social media (Facebook, Twitter, and You Tube) for advocacy by nonprofit organizations with diametrically opposed points of view on two social issues, the pro-gun/gun control issue and the prochoice/pro-life issue.
151 citations
TL;DR: In this article, the authors considered an EOQ problem under partial delayed payment, where a fraction of the purchasing cost must be paid at the beginning of the period and the remaining amount can be paid later.
Abstract: In many transactions concerning selling and buying, a specified delay of payment is offered or accepted by the seller. This can be regarded as a kind of discount and has potential consequences for the order size. These kinds of effects are not explicitly incorporated in the classical formulas for economic order quantities (EOQ). In this research we consider an EOQ problem under partial delayed payment. A fraction of the purchasing cost must be paid at the beginning of the period and the remaining amount can be paid later. Shortages are permitted and occur as a combination of backorders and lost sales. The aim of this paper is to determine the order and shortage quantities.
131 citations
TL;DR: It is found that dogs who exhibited facial expressions that enhance their neonatal appearance were preferentially selected by humans, adding to the understanding of early dog domestication as a complex co-evolutionary process.
Abstract: How wolves were first domesticated is unknown. One hypothesis suggests that wolves underwent a process of self-domestication by tolerating human presence and taking advantage of scavenging possibilities. The puppy-like physical and behavioural traits seen in dogs are thought to have evolved later, as a byproduct of selection against aggression. Using speed of selection from rehoming shelters as a proxy for artificial selection, we tested whether paedomorphic features give dogs a selective advantage in their current environment. Dogs who exhibited facial expressions that enhance their neonatal appearance were preferentially selected by humans. Thus, early domestication of wolves may have occurred not only as wolf populations became tamer, but also as they exploited human preferences for paedomorphic characteristics. These findings, therefore, add to our understanding of early dog domestication as a complex co-evolutionary process.
TL;DR: A Bayesian Change Point algorithm is introduced which provides uncertainty estimates both in the number and location of change points through an efficient probabilistic solution to the multiple change point problem.
Abstract: Given distinct climatic periods in the various facets of the Earth's climate system, many attempts have been made to determine the exact timing of ‘change points’ or regime boundaries. However, identification of change points is not always a simple task. A time series containing N data points has approximately Nk distinct placements of k change points, rendering brute force enumeration futile as the length of the time series increases. Moreover, how certain are we that any one placement of change points is superior to the rest? This paper introduces a Bayesian Change Point algorithm which provides uncertainty estimates both in the number and location of change points through an efficient probabilistic solution to the multiple change point problem. To illustrate its versatility, the Bayesian Change Point algorithm is used to analyse both the NOAA/NCDC annual global surface temperature anomalies time series and the much longer δ18O record of the Plio-Pleistocene. Copyright © 2012 Royal Meteorological Society
TL;DR: Initial efficacy favored the BPT program over the comparison group and suggested that this manualized parent training approach is worthy of further examination of the efficacy within a larger RCT.
TL;DR: The results of a computational study modeling osmotically driven endosome burst or the ‘proton sponge effect' are presented, which builds on previous cellular simulation efforts by linking the previous model with a sponge protonation model, then observing the impact on endosomal swelling and acidification.
Abstract: Dendrimers have been proposed as therapeutic gene delivery platforms. Their superior transfection efficiency is attributed to their ability to buffer the acidification of the endosome and attach to the nucleic acids. For effective transfection, the strategy is to synthesize novel dendrimers that optimize both of these traits, but the prediction of the buffering behavior in the endosome remains elusive. It is suggested that buffering dendrimers induce an osmotic pressure sufficient to rupture the endosome and release nucleic acids, which forms to sequestrate most internalized exogenous materials. Presented here are the results of a computational study modeling osmotically driven endosome burst or the ‘proton sponge effect.’ The approach builds on previous cellular simulation efforts by linking the previous model with a sponge protonation model, then observing the impact on endosomal swelling and acidification. Calibrated and validated using reported experimental data, the simulations offer insights into de...
TL;DR: The first demonstration that ω-3 PUFAs protect against white matter injury in vivo and in vitro is demonstrated, which supports the clinical use of this dietary supplement as a prophylaxis against traumatic brain injury and other nervous system disorders.
Abstract: Dietary supplementation with omega-3 (ω-3) fatty acids is a safe, economical mean of preventive medicine that has shown protection against several neurologic disorders. The present study tested the hypothesis that this method is protective against controlled cortical impact (CCI). Indeed, mice fed with ω-3 polyunsaturated fatty acid (PUFA)-enriched diet for 2 months exhibited attenuated short and long-term behavioral deficits due to CCI. Although ω-3 PUFAs did not decrease cortical lesion volume, these fatty acids did protect against hippocampal neuronal loss after CCI and reduced pro-inflammatory response. Interestingly, ω-3 PUFAs prevented the loss of myelin basic protein (MPB), preserved the integrity of the myelin sheath, and maintained the nerve fiber conductivity in the CCI model. ω-3 PUFAs also directly protected oligodendrocyte cultures from excitotoxicity and blunted the microglial activation-induced death of oligodendrocytes in microglia/oligodendrocyte cocultures. In sum, ω-3 PUFAs elicit multifaceted protection against behavioral dysfunction, hippocampal neuronal loss, inflammation, and loss of myelination and impulse conductivity. The present report is the first demonstration that ω-3 PUFAs protect against white matter injury in vivo and in vitro. The protective impact of ω-3 PUFAs supports the clinical use of this dietary supplement as a prophylaxis against traumatic brain injury and other nervous system disorders.
TL;DR: In this paper, an EOQ model with multiple prepayments under three different conditions: (a) no shortage, (b) full backordering and (c) partial backordering, are developed.
TL;DR: A novel dual-mode contrast agent formulated through the addition of an optical near infrared (NIR) probe to a perfluorocarbon (PFC)-based 19F magnetic resonance imaging (MRI) agent could serve as a valuable tool for evaluating novel anticancer agents.
Abstract: A novel dual-mode contrast agent was formulated through the addition of an optical near infrared (NIR) probe to a perfluorocarbon (PFC)-based 19F magnetic resonance imaging (MRI) agent, which labels inflammatory cells in situ. A single PFC-NIR imaging agent enables both a qualitative, rapid optical monitoring of an inflammatory state and a quantitative, detailed and tissue-depth independent magnetic resonance imaging (MRI). The feasibility of in vivo optical imaging of the inflammatory response was demonstrated in a subcutaneous murine breast carcinoma model. Ex vivo optical imaging was used to quantify the PFC-NIR signal in the tumor and organs, and results correlated well with quantitative 19F NMR analyses of intact tissues. 19F MRI was employed to construct a three-dimensional image of the cellular microenvironment at the tumor site. Flow cytometry of isolated tumor cells was used to identify the cellular localization of the PFC-NIR probe within the tumor microenvironment. Contrast is achieved through ...
TL;DR: As Scriptaid offers long-lasting neuronal and behavioral protection, even when delivered 12 h after controlled cortical impact, it is an excellent new candidate for the effective clinical treatment of TBI.
TL;DR: The concept that disruptions in mitochondrial dynamics—biogenesis, clearance, and fission/fusion events—may underlie neural diseases and thus could be targeted as neuroprotective strategies in the context of ischemic injury is put forward.
Abstract: Mitochondria play a central role in cell fate after stressors such as ischemic brain injury. The convergence of intracellular signaling pathways on mitochondria and their release of critical factors are now recognized as a default conduit to cell death or survival. Besides the individual processes that converge on or emanate from mitochondria, a mitochondrial organellar response to changes in the cellular environment has recently been described. Whereas mitochondria have previously been perceived as a major center for cellular signaling, one can postulate that the organelle's dynamics themselves affect cell survival. This brief perspective review puts forward the concept that disruptions in mitochondrial dynamics—biogenesis, clearance, and fission/fusion events—may underlie neural diseases and thus could be targeted as neuroprotective strategies in the context of ischemic injury. To do so, we present a general overview of the current understanding of mitochondrial dynamics and regulation. We then review emerging studies that correlate mitochondrial biogenesis, mitophagy, and fission/fusion events with neurologic disease and recovery. An overview of the system as it is currently understood is presented, and current assessment strategies and their limitations are discussed.
TL;DR: In this article, the authors report on the current state of ethics and compliance programs among business organizations in the United States and conclude that these programs remain vulnerable to sufficient resource allocation by the organization to be fully effective.
Abstract: This research reports on the current state of ethics and compliance programs among business organizations in the United States. Members of the Ethics and Compliance Officers Association (ECOA), the premier professional association for managers working in this field, were asked to provide in-depth responses to a series of questions covering various elements of their corporate ethics and compliance programs. The findings from this analysis indicate that ethics and compliance programs have multiple components that are implemented developmentally, are influenced by regulatory and legal efforts and have evolved into more sophisticated approaches that include risk assessment and employee performance appraisal. However, these programs remain vulnerable to sufficient resource allocation by the organization to be fully effective.
TL;DR: It is demonstrated that the immobilizing mechanism was effective in enhancing the retention of IgG locally in vivo in the in situ-forming injectable system used to enhance the delivery of immune modulatory antibodies in tumors.
Abstract: The performance of an in situ-forming injectable membrane designed to retain antibody molecules in vivo is described. The system entails an aqueous mixture of peptide amphiphiles (referred to as"EAK16-II" and "EAKH6") and intermediate proteins (anti-H6 antibody and protein A/G) through which therapeutic IgG molecules are colocalized and oriented. Scanning electron micrographs show IgG molecules localized on the EAK16-II/EAKH6 membrane. IgG were captured via specific interactions and remained biologically active in vitro. Upon administration into mice subcutaneously, the amphiphilic peptides coassembled into stable His-tags displaying materials locally. The system was shown to retain in vivo a fluorescent dye-labeled IgG in two epithelial tumor lines. IgG coadministered with the system were found to remain in 4T1 mouse mammary tumors for up to 120 h, while free antibody was cleared within the first 24 h. Decreased clearance was also found in B16 melanoma established in mouse footpads. These studies demonstrated that the immobilizing mechanism was effective in enhancing the retention of IgG locally in vivo. The injectable system may be used to enhance the delivery of immune modulatory antibodies in tumors.
TL;DR: In this article, the authors examine the ways in which teams adapt to new environments, and propose a different approach by examining the ways that teams adapt in a different way from individual adjustment, focusing on individual adjustment.
Abstract: Reviews of research on newcomers mostly address socialization processes, focusing on individual adjustment. This article takes a different approach by examining the ways in which teams adapt to new...
TL;DR: Treg treatment did not exacerbate poststroke immunosuppression and, on the contrary, Treg-treated animals displayed improved immune status after focal cerebral ischemia, which corrects long-term lymphopenia and improves cellular immune functions after ischemic brain injury.
Abstract: Background and Purpose—Cerebral ischemia has been shown to result in peripheral inflammatory responses followed by long-lasting immunosuppression. Our recent study demonstrated that intravenous delivery of regulatory T cells (Tregs) markedly protected against transient cerebral ischemia by suppressing neutrophil-derived matrix metallopeptidase 9 production in the periphery. However, the effect of Tregs on systemic inflammatory responses and immune status has not been fully characterized. Methods—Cerebral ischemia was induced by middle cerebral artery occlusion for 60 minutes in mice or 120 minutes in rats. Tregs were isolated from donor animals by CD4 and CD25 double selection and transferred intravenously to ischemic recipients at 2 hours after middle cerebral artery occlusion. Animals were euthanized on different days after reperfusion. The effects of Tregs on systemic inflammation and immune status were evaluated using flow cytometry, ELISAs, and immunohistochemistry. Results—Systemic administration of...
TL;DR: Functional health literacy was much higher than expected; however, adherence in this sample was sub-optimal, and medication adherence continues to be an issue for people living with HIV/AIDS.
Abstract: colbert a.m., sereika s.m. & erlen j.a. (2012) Functional health literacy, medication-taking self-efficacy and adherence to antiretroviral therapy. Journal of Advanced Nursing69(2), 295–304. doi: 10.1111/j.1365-2648.2012.06007.x
Abstract
Aims. To report a study of the relationship between functional health literacy and medication adherence, as mediated by medication-taking self-efficacy, while controlling for the effect of key demographic variables (such as race, income and level of education).
Background. Medication adherence is critical to successful HIV/AIDS self-management. Despite simplified regimens and the availability of tools to assist with medication-taking, adherence remains a challenge for many people living with HIV/AIDS.
Design. Cross-sectional, secondary analysis.
Methods. Data for this study of 302 adults living with HIV/AIDS who were taking antiretroviral medications were collected from January 2004–December 2007. Medication adherence was measured using electronic event monitors. Bivariate analyses and stepwise regression were conducted to examine the associations among functional health literacy, medication-taking self-efficacy and HIV medication adherence.
Results. Overall, functional health literacy was much higher than expected; however, adherence in this sample was sub-optimal. Higher medication-taking self-efficacy was associated with higher medication adherence; however, functional health literacy was not significantly related to either medication adherence or self-efficacy beliefs. Hence, medication-taking self-efficacy did not mediate the relationship between functional health literacy and medication adherence.
Conclusions. Medication adherence continues to be an issue for people living with HIV/AIDS. Additional research is needed to understand the disparate findings related to functional health literacy and medication adherence in this and other studies examining this association.
TL;DR: The BAM is not as effective as the BESS in identifying abnormal postural control in adolescents with sports concussions, but the Bess was effective in discriminating between young adults with acute concussion and young healthy people, suggesting that the test has value in the assessment of acute concussions.
Abstract: Background:High-technology methods demonstrate that balance problems may persist up to 30 days after a concussion, whereas with low-technology methods such as the Balance Error Scoring System (BESS), performance becomes normal after only 3 days based on previously published studies in collegiate and high school athletes.Purpose:To compare the National Institutes of Health’s Balance Accelerometer Measure (BAM) with the BESS regarding the ability to detect differences in postural sway between adolescents with sports concussions and age-matched controls.Study Design:Cohort study (diagnosis); Level of evidence, 2.Methods:Forty-three patients with concussions and 27 control participants were tested with the standard BAM protocol, while sway was quantified using the normalized path length (mG/s) of pelvic accelerations in the anterior-posterior direction. The BESS was scored by experts using video recordings.Results:The BAM was not able to discriminate between healthy and concussed adolescents, whereas the BESS...
TL;DR: An overview of what is happening to children with ASDs in China is given, first the issue of prevalence of ASDs is addressed, and then an introduction to the diagnostic process is offered.
Abstract: Since the late 1970s, special education in the People's Republic of China has experienced significant reform and fast development. However, education for children with severe developmental disabilities, especially autism spectrum disorders (ASDs), is still the greatest challenge in the field. This paper aims to give readers an overview of what is happening to children with ASDs in China. We first address the issue of prevalence of ASDs, and then offer an introduction to the diagnostic process. After that, a review of disability-related legislation is provided, followed by a description of current treatment options and available educational services. Finally we introduce all extent service providers and their roles.
TL;DR: PFC nanoemulsions enabling real-time optical detection of intracellular pH measurements in living cells in response to pharmacological manipulations allow the study of the fate of the PFC tracer inside the labeled cell, which is important for understanding the P FC cell loading dynamics, nanoemulsion stability and cell viability over time.
Abstract: We report the synthesis and formulation of unique perfluorocarbon (PFC) nanoemulsions enabling intracellular pH measurements in living cells via fluorescent microscopy and flow cytometry. These nanoemulsions are formulated to readily enter cells upon coincubation and contain two cyanine-based fluorescent reporters covalently bound to the PFC molecules, specifically Cy3-PFC and CypHer5-PFC conjugates. The spectral and pH-sensing properties of the nanoemulsions were characterized in vitro and showed the unaltered spectral behavior of dyes after formulation. In rat 9L glioma cells loaded with nanoemulsion, the local pH of nanoemulsions was longitudinally quantified using optical microscopy and flow cytometry and displayed a steady decrease in pH to a level of 5.5 over 3 h, indicating rapid uptake of nanoemulsion to acidic compartments. Overall, these reagents enable real-time optical detection of intracellular pH in living cells in response to pharmacological manipulations. Moreover, recent approaches for in...
TL;DR: This paper develops EOQ models with a known price increase and partial backordering under two different assumptions about when the increase will occur, and proves the concavity of the extra profit functions for both scenarios if a special order is placed just before the price increases.
TL;DR: OrangFACS, a FACS adapted for orangutans, is presented, indicating an overall facial mobility similar to that found in chimpanzees, macaques, and gibbons but smaller than thatFindings indicate the need for facial communication in specialized contexts, phylogenetic inertia, and allometric effects.
Abstract: Comparing homologous expressions between species can shed light on the phylogenetic and functional changes that have taken place during evolution. To assess homology across species we must approach primate facial expressions in an anatomical, systematic, and standardized way. The Facial Action Coding System (FACS), a widely used muscle-based tool for analyzing human facial expressions, has recently been adapted for chimpanzees (Pan troglodytes: ChimpFACS), rhesus macaques (Macaca mulatta: MaqFACS), and gibbons (GibbonFACS). Here, we present OrangFACS, a FACS adapted for orangutans (Pongo spp.). Orangutans are the most arboreal and the least social great ape, so their visual communication has been assumed to be less important than vocal communication and is little studied. We scrutinized the facial anatomy of orangutans and coded videos of spontaneous orangutan behavior to identify independent movements: Action Units (AUs) and Action Descriptors (ADs). We then compared these facial movements with movements of homologous muscles in humans, chimpanzees, macaques, and gibbons. We also noted differences related to sexual dimorphism and developmental stages in orangutan facial morphology. Our results show 17 AUs and 7 ADs in orangutans, indicating an overall facial mobility similar to that found in chimpanzees, macaques, and gibbons but smaller than that found in humans. This facial movement capacity in orangutans may be the result of several, nonmutually exclusive explanations, including the need for facial communication in specialized contexts, phylogenetic inertia, and allometric effects.
TL;DR: The James L. Waters Symposium 2012 as mentioned in this paper had five invited speakers to describe the development and commercialization of portable, hand-held X-ray fluorescence (XRF) spectrometers.
Abstract: The James L. Waters Symposium 2012 had five invited speakers to describe the development and commercialization of portable, hand-held X-ray fluorescence (XRF) spectrometers. Lee Grodzins described the birth and the maturation of hand-held XRF (HHXRF) spectrometers. Andrew Ellis described how the stainless-steel industry in Finland led to the development of X-MET HHXRF analyzers. Charles Jensen reviewed the performance improvements in miniature X-ray sources made by his company, Moxtek. Alan Huber explained how his company, Amptek, led the development of detectors for HHXRF. Stanislaw Piorek detailed the evolution of analytical capabilities of field-portable, HHXRF analyzers.