Eyeing the past: synchrotron µ-XANES and XRF imaging of tarnish distribution on 19th century daguerreotypes.

Louis-Jacques-Mandé Daguerre introduced the first successful photographic process, the daguerreotype, in 1839. Tarnished regions on daguerreotypes supplied by the National Gallery of Canada were examined using scanning electron microscopy energy-dispersive X-ray spectroscopy and synchrotron-radiation analysis. Synchrotron X-ray fluorescence imaging visualized the distribution of sulfur and chlorine, two primary tarnish contributors, and showed that they were associated with the distribution of image particles on the surface. X-ray absorption near-edge structure spectroscopy determined the tarnish to be primarily composed of AgCl and Ag2S. Au2S, Au2SO4, HAuCl4 and HgSO4 were also observed to be minor contributors. Environmental contamination may be a source of these degradation compounds. Implications of these findings will be discussed.

Localization microscopy: mapping cellular dynamics with single molecules.

Resolution describes the smallest details within a sample that can be recovered by a microscope lens system. For optical microscopes detecting visible light, diffraction limits the resolution to ∼200-250 nm. In contrast, localization measures the position of an isolated object using its image. Single fluorescent molecules can be localized with an uncertainty of a few tens of nanometres, and in some cases less than one nanometre. Superresolution fluorescence localization microscopy (SRFLM) images and localizes fluorescent molecules in a sample. By controlling the visibility of the fluorescent molecules with light, it is possible to cause a sparse subset of the tags to fluoresce and be spatially separated from each other. A movie is acquired with a camera, capturing images of many sets of visible fluorescent tags over a period of time. The movie is then analysed by a computer whereby all of the single molecules are independently measured, and their positions are recorded. When the coordinates of a sufficient number of molecules are collected, an image can be rendered by plotting the coordinates of the localized molecules. The spatial resolution of these rendered images can be better than 20 nm, roughly an order of magnitude better than the diffraction limited resolution. The invention of SRFLM has led to an explosion of related techniques. Through the use of specialized optics, the fluorescent signal can be split into multiple detection channels. These channels can capture additional information such as colour (emission wavelength), orientation and three-dimensional position of the detected molecules. Measurement of the colour of the detected fluorescence can allow researchers to distinguish multiple types of fluorescent tags and to study the interaction between multiple molecules of interest. Three-dimensional imaging and determination of molecular orientations offer insight into structural organization of the sample. SRFLM is compatible with living samples and has helped to illuminate many dynamic biological processes, such as the trajectories of molecules within living cells. This review discusses the concept and process of SRFLM imaging and investigates recent advances in SRFLM functionality. Since its announcement in 2006, SRFLM has been quickly adopted and modified by many researchers to help investigate questions whose answers lie below the diffraction limit. The versatility of the SRFLM technique has great promise for improving our understanding of cell biology at the molecular level.

Fit for Duty: Lessons Learned from Outpatient and Homebound Hematopoietic Cell Transplantation to Prepare Family Caregivers for Home-Based Care.

In the past decade, the demand for home-based care has been amplified by the Coronavirus disease 2019 pandemic. Home-based care has significant benefits for patients, their families, and healthcare systems, but it relies on the often-invisible workforce of family and friend caregivers who shoulder essential health care responsibilities, frequently with inadequate training and support. Hematopoietic cell transplantation (HCT), a potentially curative but intensive treatment for many patients with blood disorders, is being increasingly offered in home-based care settings and necessitates the involvement of family caregivers for significant patient care responsibilities. However, guidelines for supporting and preparing HCT caregivers to effectively care for their loved ones at home have not yet been established. Here, informed by the literature and our collective experience as clinicians and researchers who care for diverse patients with hematologic malignancies undergoing HCT, we provide considerations and recommendations to better support and prepare family caregivers in home-based HCT and, by extension, family caregivers supporting patients with other serious illnesses at home. We suggest tangible ways to screen family caregivers for distress and care delivery challenges, educate and train them to prepare for their caregiving role, and create an infrastructure of support for family caregivers within this emerging care delivery model.

Ultrafast shock compression and shock-induced decomposition of 1,3,5-triamino-2,4,6-trinitrobenzene subjected to a subnanosecond-duration shock: an analysis of decomposition products.

Shock compression studies of pressed and confined ultrafine 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) powder were conducted using ultrashort ~300 ps, ~50 GPa shock waves. The recovered decomposition products were characterized using X-ray photoelectron spectroscopy, infrared spectroscopy, and Raman spectroscopy. A substantial amount of shock-related chemistry was observed. Approximately 75% of the nitrogen atoms were liberated as gas-phase species, along with ~33% of the oxygen atoms, as a result of the applied shock. Furthermore, we observe C 1s binding energies suggesting the formation of sp(3) hybridized amorphous carbon. For comparison, a carbon nitride material was also prepared and characterized by thermally pyrolizing TATB. The shock-compressed TATB and the thermally pyrolized TATB are qualitatively different, suggesting that, carbon nitrides, a possible indicator of nitrogen-rich heterocycles precursors, are not a major product class for strongly overdriven shock conditions. These experimental conditions were, however, not detonation conditions, and the possible formation of nitrogen-rich heterocycles in actual detonations still exists.

Plasticity-inducing TMS protocols to investigate somatosensory control of hand function.

Hand function depends on sensory feedback to direct an appropriate motor response. There is clear evidence that somatosensory cortices modulate motor behaviour and physiology within primary motor cortex. However, this information is mainly from research in animals and the bridge to human hand control is needed. Emerging evidence in humans supports the notion that somatosensory cortices modulate motor behaviour, physiology and sensory perception. Transcranial magnetic stimulation (TMS) allows for the investigation of primary and higher-order somatosensory cortices and their role in control of hand movement in humans. This review provides a summary of several TMS protocols in the investigation of hand control via the somatosensory cortices. TMS plasticity inducing protocols reviewed include paired associative stimulation, repetitive TMS, theta-burst stimulation as well as other techniques that aim to modulate cortical excitability in sensorimotor cortices. Although the discussed techniques may modulate cortical excitability, careful consideration of experimental design is needed to isolate factors that may interfere with desired results of the plasticity-inducing protocol, specifically events that may lead to metaplasticity within the targeted cortex.

Multivessel coronary artery spasm.

Coronary spasm is increasingly recognised as an important aetiological mechanism causing myocardial ischaemia. Occasionally cases present with evidence of ST segment elevation myocardial infarction, usually secondary to spasm confined to a solitary coronary artery. We present the rare and life-threatening case of severe coronary spasm afflicting all three major epicardial arteries simultaneously. It describes the difficult emergency scenario and ongoing management dilemmas encountered by physicians confronted with multivessel coronary spasm. Moreover we discuss the malignant prognosis associated with this ailment and describe the potential insights provided by cardiac magnetic resonance imaging that might identify those at greatest risk after the index event.

Electronic structure of warm dense copper studied by ultrafast x-ray absorption spectroscopy.

We use time-resolved x-ray absorption spectroscopy to investigate the unoccupied electronic density of states of warm dense copper that is produced isochorically through the absorption of an ultrafast optical pulse. The temperature of the superheated electron-hole plasma, which ranges from 4000 to 10 000 K, was determined by comparing the measured x-ray absorption spectrum with a simulation. The electronic structure of warm dense copper is adequately described with the high temperature electronic density of state calculated by the density functional theory. The dynamics of the electron temperature is consistent with a two-temperature model, while a temperature-dependent electron-phonon coupling parameter is necessary.

Decay of cystalline order and equilibration during the solid-to-plasma transition induced by 20-fs microfocused 92-eV free-electron-laser pulses.

We have studied a solid-to-plasma transition by irradiating Al foils with the FLASH free electron laser at intensities up to 10(16) W/cm(2). Intense XUV self-emission shows spectral features that are consistent with emission from regions of high density, which go beyond single inner-shell photoionization of solids. Characteristic features of intrashell transitions allowed us to identify Auger heating of the electrons in the conduction band occurring immediately after the absorption of the XUV laser energy as the dominant mechanism. A simple model of a multicharge state inverse Auger effect is proposed to explain the target emission when the conduction band at solid density becomes more atomiclike as energy is transferred from the electrons to the ions. This allows one to determine, independent of plasma simulations, the electron temperature and density just after the decay of crystalline order and to characterize the early time evolution.

Characterization and cloning of a novel glycoprotein expressed by stromal cells in T-dependent areas of peripheral lymphoid tissues.

A novel glycoprotein (gp) expressed by stromal cells of peripheral lymphoid tissue has been characterized immunohistochemically, biochemically, and at the molecular level. This molecule, gp38, was identified with a monoclonal antibody (mAb) (clone 8.1.1) previously shown to react with a subpopulation of thymic epithelium. This mAb generated a reticular labeling pattern in medullary and paracortical areas of lymph nodes and in splenic white pulp. At the ultrastructural level, labeling by the 8.1.1 mAb was restricted to fibroblastic reticular stromal cells. Serial sections of lymph node and spleen labeled with anti-CD3, anti-B220, and 8.1.1 mAbs clearly showed that the 8.1.1+ cells were associated with T cell-dependent areas. In severe combined immunodeficiency (SCID) or Nu/Nu mice, splenic white pulp also exhibited reticular labeling with the 8.1.1 mAb in the absence of detectable numbers of T cells, indicating that the appearance of 8.1.1-reactive stromal cells in discrete areas of peripheral lymphoid tissue was T cell independent. The cDNA encoding this stromal cell molecule was cloned by direct expression in COS cells and found to encode a 172 amino acid sequence with the typical features of a type I integral membrane protein. COS cells transfected with the gp38 clone direct the expression of an approximately 38-kD protein that reacts with the 8.1.1 mAb but not with isotype-matched controls. Comparison of the predicted amino acid sequence of 8.1.1 mAb but not with isotype-matched controls. Comparison of the predicted amino acid sequence of 8.1.1 with proteins in the National Biomedical Research Foundation (NBRF) data base showed that gp38 is very closely related to the early response protein OTS-8 obtained from a cDNA library of tumor promoting agent (TPA)-induced murine osteoblastic cell line, MC3T3-E1.

Synchrotron radiation analysis of possible correlations between metal status in human cementum and periodontal disease.

Periodontitis is a serious disease that affects up to 50% of an adult population. It is a chronic condition involving inflammation of the periodontal ligament and associated tissues leading to eventual tooth loss. Some evidence suggests that trace metals, especially zinc and copper, may be involved in the onset and severity of periodontitis. Thus we have used synchrotron X-ray fluorescence imaging on cross sections of diseased and healthy teeth using a microbeam to explore the distribution of trace metals in cementum and adhering plaque. The comparison between diseased and healthy teeth indicates that there are elevated levels of zinc, copper and nickel in diseased teeth as opposed to healthy teeth. This preliminary correlation between elevated levels of trace metals in the cementum and plaque of diseased teeth suggests that metals may play a role in the progress of periodontitis.

Electronic structure of an XUV photogenerated solid-density aluminum plasma.

By use of high intensity XUV radiation from the FLASH free-electron laser at DESY, we have created highly excited exotic states of matter in solid-density aluminum samples. The XUV intensity is sufficiently high to excite an inner-shell electron from a large fraction of the atoms in the focal region. We show that soft-x-ray emission spectroscopy measurements reveal the electronic temperature and density of this highly excited system immediately after the excitation pulse, with detailed calculations of the electronic structure, based on finite-temperature density functional theory, in good agreement with the experimental results.

An Investigation of Micro-CT Analysis of Bone as a New Diagnostic Method for Paleopathological Cases of Osteomalacia.

OBJECTIVE: This paper looks to broaden the methodological possibilities for diagnosing osteomalacia in archaeological bone using micro-CT analysis. Increasing the identification of osteomalacia in paleopathology will provide support for important interpretive frameworks. MATERIALS: Nine embedded and two unembedded rib fragments were sourced from St. Martin's Birmingham and Ancaster, UK, and Lisieux Michelet, France. Of the 11 samples, nine were previously confirmed as osteomalacic, and presented with varying levels of diagenesis and two were non-osteomalacic controls, one of which exhibits diagenetic change. METHODS: Micro-CT, backscattered scanning electron microscopy, and light microscopy were employed. Micro-CT images were evaluated for osteomalacic features using corresponding microscopic images. RESULTS: Micro-CT images from osteomalacic samples demonstrated the presence of defective mineralization adjacent to cement lines, areas of incomplete mineralization, and resorptive bays/borders, three key diagnostic features of osteomalacia. Diagenetic change was also detectable in micro-CT images, but did not prevent the diagnosis of osteomalacia. CONCLUSIONS: Micro-CT analysis is a non-destructive method capable of providing microstructural images of osteomalacic features in embedded and unembedded samples. When enough of these features are present, micro-CT images are capable of confirming a diagnosis of osteomalacia. SIGNIFICANCE: Vitamin D deficiency has important health consequences which operate throughout the life course. Increasing the ability to detect cases of vitamin D deficiency provides researchers with a greater understanding of health and disease in past communities. LIMITATIONS: Only adult rib samples were used. SUGGESTIONS FOR FURTHER RESEARCH: Paleopathologists should look to test the utility of micro-CT analysis in diagnosing active rickets in subadult individuals.

Organic dust-induced lung injury and repair: Bi-directional regulation by TNFα and IL-10.

Exposure to organic dust increases chronic airway inflammatory disorders. Effective treatment strategies are lacking. It has been reported that hog barn dust extracts (HDE) induce TNFα through protein kinase C (PKC) activation and that lung inflammation is enhanced in scavenger receptor A (SRA/CD204) knockout (KO) mice following HDE. Because interleukin (IL)-10 production can limit excessive inflammation, it was hypothesized here that HDE-induced IL-10 would require CD204 to effect inflammatory responses. C57BL/6 wild-type (WT), SRA KO, and IL-10 KO mice were intranasally challenged daily for 8 days with HDE and subsequently rested for 3 days with/without recombinant IL-10 (rIL-10) treatment. Primary peritoneal macrophages (PM) and murine alveolar macrophages (MH-S cells) were treated in vitro with HDE, SRA ligand (fucoidan), rIL-10, and/or PKC isoform inhibitors. HDE induced in vivo lung IL-10 in WT, but not SRA KO mice, and similar trends were demonstrated in isolated PM from same treated mice. Lung lymphocyte aggregates and neutrophils were elevated in in vivo HDE-treated SRA and IL-10 KO mice after a 3-d recovery, and treatment during recovery with rIL-10 abrogated these responses. In vitro rIL-10 treatment reduced HDE-stimulated TNFα release in MH-S and WT PM. In SRA KO macrophages, there was reduced IL-10 and PKC zeta (ζ) activity and increased TNFα following in vitro HDE stimulation. Similarly, blocking SRA (24 hr fucoidan pre-treatment) resulted in enhanced HDE-stimulated macrophage TNFα and decreased IL-10 and PKCζ activation. PKCζ inhibitors blocked HDE-stimulated IL-10, but not TNFα. Collectively, HDE stimulates IL-10 by an SRA- and PKCζ-dependent mechanism to regulate TNFα. Enhancing resolution of dust-mediated lung inflammation through targeting IL-10 and/or SRA may represent new approaches to therapeutic interventions.

Carbon nanotubes promote neuron differentiation from human embryonic stem cells.

Human embryonic stem cells (hESCs) hold great promise for regenerative medicine and transplantation therapy due to their self-renewal and pluripotent properties. We report that 2D thin film scaffolds composed of biocompatible polymer grafted carbon nanotubes (CNTs), can selectively differentiate human embryonic stem cells into neuron cells while maintaining excellent cell viability. According to fluorescence image analysis, neuron differentiation efficiency of poly(acrylic acid) grafted CNT thin films is significant greater than that on poly(acrylic acid) thin films. When compared with the conventional poly-L-ornithine surfaces, a standard substratum commonly used for neuron culture, this new type thin film scaffold shows enhanced neuron differentiation. No noticeable cytotoxic effect difference has been detected between these two surfaces. The surface analysis and cell adhesion study have suggested that CNT-based surfaces can enhance protein adsorption and cell attachment. This finding indicates that CNT-based materials are excellent candidates for hESCs' neuron differentiation.

Soft x-ray free electron laser microfocus for exploring matter under extreme conditions.

We have focused a beam (BL3) of FLASH (Free-electron LASer in Hamburg: lambda = 13.5 nm, pulse length 15 fs, pulse energy 10-40 microJ, 5 Hz) using a fine polished off-axis parabola having a focal length of 270 mm and coated with a Mo/Si multilayer with an initial reflectivity of 67% at 13.5 nm. The OAP was mounted and aligned with a picomotor controlled six-axis gimbal. Beam imprints on poly(methyl methacrylate) - PMMA were used to measure focus and the focused beam was used to create isochoric heating of various slab targets. Results show the focal spot has a diameter of < or =1 microm. Observations were correlated with simulations of best focus to provide further relevant information.

Data showing regional differences in rat brain monoaminergic function.

Chemical neurotransmitters (such as dopamine) modulate cognitive function via ascending projections to various cortical and sub-cortical brain regions. This report describes and links to a relatively large dataset (up to N = 112) compiled from control (untreated) brain samples taken during a series of experimental in vivo studies. The dataset is freely available, to explore the normal interrelationships between levels of neurotransmitter (e.g., dopamine, serotonin), across brain regions implicated in both normal reward and drug addiction, as well as in disorders such as schizophrenia (e.g., nucleus accumbens, prefrontal cortex). Most experimental studies run with a relatively small control group, so there is a lack of baseline data on the expected levels of neurotransmitters and their metabolites in different brain regions. Accordingly, the available dataset has been compiled from a number of studies run in the same laboratory, and using closely similar behavioural procedures, sampling selected brain regions of a priori interest. These collated data can be used to explore differences in the distribution of the monoamines and their metabolites, patterns of neurotransmitter intercorrelations, both between and within different brain structures and including some consideration of laterality effects.

Molecular imaging with neural training of identification algorithm (neural network localization identification).

Superresolution localization microscopy strongly relies on robust identification algorithms for accurate reconstruction of the biological systems it is used to measure. The fields of machine learning and computer vision have provided promising solutions for automated object identification, but usually rely on well represented training sets to learn object features. However, using a static training set can result in the learned identification algorithm making mistakes on data that is not well represented by the training set. Here, we present a method for training an artificial neural network without providing a training set in advance. This method uses the data to be analyzed, and the fitting algorithm to train an artificial neural network tailored to that data set. We show that the same artificial neural network can learn to identify at least two types of molecular emissions: the regular point spread functions (PSFs), and the astigmatism PSF. Simulations indicate that this method can be extremely reliable in extracting molecular emission signatures. Additionally, we implemented the artificial neural network calculation to be performed on a graphics processing unit (GPU) for massively parallelized calculation which drastically reduces the time required for the identification process. By implementing the neural identification on a GPU, we allow this method of identification to be used in a real time analysis algorithm. RESEARCH HIGHLIGHTS: Here, we present a machine learning algorithm for identifying point-spread functions without the need for an a priori training set. We show that this method can detect over 90% of molecules with less than 1% false positive identification in simulations. We further show that because this algorithm does not make assumptions of about the shape of molecular emission, it is compatible with models beyond the symmetric 2D Gaussian.

The relationship between skin temperature and neuronal characteristics in the median, ulnar and radial nerves of non-impaired individuals.

The purpose of this study was to evaluate the relationship between the nerve conduction characteristics in the median, ulnar and radial nerves and presenting skin temperature in non-impaired individuals as they were subjected to electrophysiological testing. Previous researchers artificially manipulated the skin temperature and demonstrated that there was a positive relationship between temperature and nerve conduction velocity and a negative correlation between distal latency and evoked motor action potential (EMAP). The sample population was 50 non-impaired individuals derived from a venue in the New York City and Long Island region. The independent variable was skin temperature. The dependent variables were: motor nerve conduction velocity, motor distal latency, EMAP of median and ulnar nerves, sensory distal latency and sensory nerve action potential (SNAP) of median, ulnar and radial nerves. The data were analyzed using descriptive statistics, the Bonferroni correction factor and correlation statistics. The study showed significant correlation in median motor distal latency, ulnar motor distal latency, ulnar sensory distal latency, median sensory amplitude, and ulnar sensory amplitude. The NCV, the distal latency and the amplitude of the median, ulnar and radial nerves were similar in values to other researchers' normal values.

The origins of individual differences in how learning is expressed in rats: A general-process perspective.

Laboratory rats can exhibit marked, qualitative individual differences in the form of acquired behaviors. For example, when exposed to a signal-reinforcer relationship some rats show marked and consistent changes in sign-tracking (interacting with the signal; e.g., a lever) and others show marked and consistent changes in goal-tracking (interacting with the location of the predicted reinforcer; e.g., the food well). Here, stable individual differences in rats' sign-tracking and goal-tracking emerged over the course of training, but these differences did not generalize across different signal-reinforcer relationships (Experiment 1). This selectivity suggests that individual differences in sign- and goal-tracking reflect differences in the value placed on individual reinforcers. Two findings provide direct support for this interpretation: the palatability of a reinforcer (as measured by an analysis of lick-cluster size) was positively correlated with goal-tracking (and negatively correlated with sign-tracking); and sating rats with a reinforcer affected goal-tracking but not sign-tracking (Experiment 2). These results indicate that the observed individual differences in sign- and goal-tracking behavior arise from the interaction between the palatability or value of the reinforcer and processes of association as opposed to dispositional differences (e.g., in sensory processes, "temperament," or response repertoire). (PsycINFO Database Record

Cortical and corticospinal output modulations during reaching movements with varying directions and magnitudes of interaction torques.

The neural command required to coordinate a multi-joint movement is inherently complex. During multi-joint movement of the limb, the force created from movement at one joint may create a torque at a second joint known as an interaction torque. Interaction torques may be assistive or resistive thereby aiding or opposing the motion of the second joint, respectively. For movement to be effectively controlled, the central nervous system should modulate neural output to the muscles to appropriately account for interaction torques. The present study examined the neural output from the primary motor cortex before and during reaching movements that required different combinations of assistive and resistive interaction torques occurring at the shoulder and elbow joints. Using transcranial magnetic stimulation to probe neural output from the primary motor cortex, results indicate that corticospinal output controlling the upper arm is related to resistive interaction torques occurring at the shoulder joint. Further, cortical output to bi-articular muscles is associated with interaction torque and this may be driven by the fact that these muscles are in an advantageous position to control torques produced between inter-connection segments. Humans have a tendency to avoid reaching movements that involve resistive interaction torques and this may be driven by the requirement of increased neural output associated with these movements.