Human KCNQ5 de novo mutations underlie epilepsy and intellectual disability.

We identified six novel de novo human KCNQ5 variants in children with motor/language delay, intellectual disability (ID), and/or epilepsy by whole exome sequencing. These variants, comprising two nonsense and four missense alterations, were functionally characterized by electrophysiology in HEK293/CHO cells, together with four previously reported KCNQ5 missense variants (Lehman A, Thouta S, Mancini GM, Naidu S, van Slegtenhorst M, McWalter K, Person R, Mwenifumbo J, Salvarinova R; CAUSES Study; EPGEN Study; Guella I, McKenzie MB, Datta A, Connolly MB, Kalkhoran SM, Poburko D, Friedman JM, Farrer MJ, Demos M, Desai S, Claydon T. Am J Hum Genet 101: 65-74, 2017). Surprisingly, all eight missense variants resulted in gain of function (GOF) due to hyperpolarized voltage dependence of activation or slowed deactivation kinetics, whereas the two nonsense variants were confirmed to be loss of function (LOF). One severe GOF allele (P369T) was tested and found to extend a dominant GOF effect to heteromeric KCNQ5/3 channels. Clinical presentations were associated with altered KCNQ5 channel gating: milder presentations with LOF or smaller GOF shifts in voltage dependence [change in voltage at half-maximal conduction (ΔV50) = ∼-15 mV] and severe presentations with larger GOF shifts in voltage dependence (ΔV50 = ∼-30 mV). To examine LOF pathogenicity, two Kcnq5 LOF mouse lines were created with CRISPR/Cas9. Both lines exhibited handling- and thermal-induced seizures and abnormal cortical EEGs consistent with epileptiform activity. Our study thus provides evidence for in vivo KCNQ5 LOF pathogenicity and strengthens the contribution of both LOF and GOF mutations to global pediatric neurological impairment, including ID/epilepsy.NEW & NOTEWORTHY Six novel de novo human KCNQ5 variants were identified from children with neurodevelopmental delay, intellectual disability, and/or epilepsy. Expression of these variants along with four previously reported KCNQ5 variants from a similar cohort revealed GOF potassium channels, negatively shifted in V50 of activation and/or delayed deactivation kinetics. GOF is extended to KCNQ5/3 heteromeric channels, making these the predominant channels affected in heterozygous de novo patients. Kcnq5 LOF mice exhibited seizures, consistent with in vivo pathogenicity.

AUTS2 Regulates RNA Metabolism and Dentate Gyrus Development in Mice.

Human AUTS2 mutations are linked to a syndrome of intellectual disability, autistic features, epilepsy, and other neurological and somatic disorders. Although it is known that this unique gene is highly expressed in developing cerebral cortex, the molecular and developmental functions of AUTS2 protein remain unclear. Using proteomics methods to identify AUTS2 binding partners in neonatal mouse cerebral cortex, we found that AUTS2 associates with multiple proteins that regulate RNA transcription, splicing, localization, and stability. Furthermore, AUTS2-containing protein complexes isolated from cortical tissue bound specific RNA transcripts in RNA immunoprecipitation and sequencing assays. Deletion of all major functional isoforms of AUTS2 (full-length and C-terminal) by conditional excision of exon 15 caused breathing abnormalities and neonatal lethality when Auts2 was inactivated throughout the developing brain. Mice with limited inactivation of Auts2 in cerebral cortex survived but displayed abnormalities of cerebral cortex structure and function, including dentate gyrus hypoplasia with agenesis of hilar mossy neurons, and abnormal spiking activity on EEG. Also, RNA transcripts that normally associate with AUTS2 were dysregulated in mutant mice. Together, these findings indicate that AUTS2 regulates RNA metabolism and is essential for development of cerebral cortex, as well as subcortical breathing centers.

Plastome phylogeography in two African rain forest legume trees reveals that Dahomey Gap populations originate from the Cameroon volcanic line.

Paleo-environmental data show that the distribution of African rain forests was affected by Quaternary climate changes. In particular, the Dahomey Gap (DG) - a 200 km wide savanna corridor currently separating the West African and Central African rain forest blocks and containing relict rain forest fragments - was forested during the mid-Holocene and possibly during previous interglacial periods, whereas it was dominated by open vegetation (savanna) during glacial periods. Genetic signatures of past population fragmentation and demographic changes have been found in some African forest plant species using nuclear markers, but such events appear not to have been synchronous or shared across species. To better understand the colonization history of the DG by rain forest trees through seed dispersal, the plastid genomes of two widespread African forest legume trees, Anthonotha macrophylla and Distemonanthus benthamianus, were sequenced in 47 individuals for each species, providing unprecedented phylogenetic resolution of their maternal lineages (857 and 115 SNPs, respectively). Both species exhibit distinct lineages separating three regions: 1. Upper Guinea (UG, i.e. the West African forest block), 2. the area ranging from the DG to the Cameroon volcanic line (CVL), and 3. Lower Guinea (LG, the western part of the Central African forest block) where three lineages co-occur. In both species, the DG populations (including southern Nigeria west of Cross River) exhibit much lower genetic diversity than UG and LG populations, and their plastid lineages originate from the CVL, confirming the role of the CVL as an ancient forest refuge. Despite the similar phylogeographic structures displayed by A. macrophylla and D. benthamianus, molecular dating indicates very contrasting ages of lineage divergence (UG diverged from LG since c. 7 Ma and 0.7 Ma, respectively) and DG colonization (probably following the Mid Pleistocene Transition and the Last Glacial Maximum, respectively). The stability of forest refuge areas and repeated similar forest shrinking/expanding events during successive glacial periods might explain why similar phylogeographic patterns can be generated over contrasting timescales.

Specific deletion of NaV1.1 sodium channels in inhibitory interneurons causes seizures and premature death in a mouse model of Dravet syndrome.

Heterozygous loss-of-function mutations in the brain sodium channel Na(V)1.1 cause Dravet syndrome (DS), a pharmacoresistant infantile-onset epilepsy syndrome with comorbidities of cognitive impairment and premature death. Previous studies using a mouse model of DS revealed reduced sodium currents and impaired excitability in GABAergic interneurons in the hippocampus, leading to the hypothesis that impaired excitability of GABAergic inhibitory neurons is the cause of epilepsy and premature death in DS. However, other classes of GABAergic interneurons are less impaired, so the direct cause of hyperexcitability, epilepsy, and premature death has remained unresolved. We generated a floxed Scn1a mouse line and used the Cre-Lox method driven by an enhancer from the Dlx1,2 locus for conditional deletion of Scn1a in forebrain GABAergic neurons. Immunocytochemical studies demonstrated selective loss of Na(V)1.1 channels in GABAergic interneurons in cerebral cortex and hippocampus. Mice with this deletion died prematurely following generalized tonic-clonic seizures, and they were equally susceptible to thermal induction of seizures as mice with global deletion of Scn1a. Evidently, loss of Na(V)1.1 channels in forebrain GABAergic neurons is both necessary and sufficient to cause epilepsy and premature death in DS.

Emergency centre patients in the Democratic Republic of Congo: Some epidemiological and clinical aspects at Beni General Referral Hospital.

Introduction: Little information is available regarding the characteristics of patients attending the emergency centre (EC) in the Democratic Republic of Congo. This study aims to provide some epidemiological and clinical aspects of patients admitted to the emergency centre at Beni General Referral Hospital. Methodology: For a year, from January to December 2021, a cross-sectional study was conducted. Data regarding patients' characteristics, admission modality, stay duration, reason for admission, and discharge modality was anonymously collected from patients' registers. A descriptive analysis was done with Epi-Info 7. Result: A total of 1404 patients were admitted to the EC, with a male-to-female ratio of 1.2 to 1. The age group below 18 years accounted for 35.4%. Most of the patients (75.7%) originated from urban areas. In 83% of cases, there was no recommendation from another medical facility for EC admission. The most common reasons for admission are non-traumatic gathering on top of neuropsychiatric and non-specific symptoms. Road traffic accidents are the most frequent causes of trauma symptoms. Few patients (14.7%) spent less than 12 hours in the EC. Globally, 7.3% of patients admitted to the EC were discharged after being managed, and 89% were transferred to different wards. The intra-emergency centre mortality rate was 11.8% among admitted patients in the ER at Beni General Referral Hospital. Conclusion: This epidemiology database underlines the need for developing globalizing and multi-sectoral interventions (diagnosis, therapeutic strategy, organization, health program, or health policies) in the perspective of bringing change and/or taking action in the Democratic Republic of Congo's emergency medical system.

AAV-mediated interneuron-specific gene replacement for Dravet syndrome.

Dravet syndrome (DS) is a devastating developmental epileptic encephalopathy marked by treatment-resistant seizures, developmental delay, intellectual disability, motor deficits, and a 10-20% rate of premature death. Most DS patients harbor loss-of-function mutations in one copy of SCN1A , which has been associated with inhibitory neuron dysfunction. Here we developed an interneuron-targeting AAV human SCN1A gene replacement therapy using cell class-specific enhancers. We generated a split-intein fusion form of SCN1A to circumvent AAV packaging limitations and deliver SCN1A via a dual vector approach using cell class-specific enhancers. These constructs produced full-length Na V 1.1 protein and functional sodium channels in HEK293 cells and in brain cells in vivo . After packaging these vectors into enhancer-AAVs and administering to mice, immunohistochemical analyses showed telencephalic GABAergic interneuron-specific and dose-dependent transgene biodistribution. These vectors conferred strong dose-dependent protection against postnatal mortality and seizures in two DS mouse models carrying independent loss-of-function alleles of Scn1a, at two independent research sites, supporting the robustness of this approach. No mortality or toxicity was observed in wild-type mice injected with single vectors expressing either the N-terminal or C-terminal halves of SCN1A , or the dual vector system targeting interneurons. In contrast, nonselective neuronal targeting of SCN1A conferred less rescue against mortality and presented substantial preweaning lethality. These findings demonstrate proof-of-concept that interneuron-specific AAV-mediated SCN1A gene replacement is sufficient for significant rescue in DS mouse models and suggest it could be an effective therapeutic approach for patients with DS.

Proceedings of the Sleep and Epilepsy Workshop: Section 3 Mortality: Sleep, Night, and SUDEP.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. Likely pathophysiological mechanisms include seizure-induced cardiac and respiratory dysregulation. A frequently identified feature in SUDEP cases is that they occur at night. This raises the question of a role for sleep state in regulating of SUDEP. An association with sleep has been identified in a number of studies with patients and in animal models. The focus of this section of the Sleep and Epilepsy Workshop was on identifying and understanding the role for sleep and time of day in the pathophysiology of SUDEP.

The Challenges of Managing Ovarian Cancer in the Developing World.

Ovarian cancer has high morbidity and mortality rates among cancers of the reproductive system. The disease typically presents at late stage when the 5-year relative survival rate is only 29%. Similarly, access to prevention, early diagnosis, treatment, and palliative care for cancer-related disease is insufficient. The availability of cancer treatments in Africa is especially poor. Case. A 17-year-old lady, nulliparous, was admitted with complaint of abdominal swelling and loss of weight and a huge left ovarian cyst revealed by ultrasound scan. Laparotomy was done, and a mass which resembled a hemorrhagic solid tumor was found. Grossly, the left ovarian mass measured 15.0 × 20.0 × 8.0 cm and a left salpingectomy was performed. Two months later, she came back with lower limb swelling progressively increased in a week with vulvar edema, with a palpable mass. She was discharged on request by her relatives for traditional medicine. One year later, she passed on in an unrevealed picture. The management of ovarian cancer is too challenging in low-resource countries, from hospital settings to the communities with poor cancer awareness. It is therefore imperative that healthcare resources, policies, and planning focus to be coordinated in a rational way.

Emergency centre patients in the Democratic Republic of Congo: Some epidemiological and clinical aspects at Beni General Referral Hospital

Introduction: Little information is available regarding the characteristics of patients attending the emergency centre (EC) in the Democratic Republic of Congo. This study aims to provide some epidemiological and clinical aspects of patients admitted to the emergency centre at Beni General Referral Hospital. Methodology: For a year, from January to December 2021, a cross-sectional study was conducted. Data regarding patients' characteristics, admission modality, stay duration, reason for admission, and discharge modality was anonymously collected from patients' registers. A descriptive analysis was done with Epi-Info 7. Result: A total of 1404 patients were admitted to the EC, with a male-to-female ratio of 1.2 to 1. The age group below 18 years accounted for 35.4%. Most of the patients (75.7%) originated from urban areas. In 83% of cases, there was no recommendation from another medical facility for EC admission. The most common reasons for admission are non-traumatic gathering on top of neuropsychiatric and non-specific symptoms. Road traffic accidents are the most frequent causes of trauma symptoms. Few patients (14.7%) spent less than 12 hours in the EC. Globally, 7.3% of patients admitted to the EC were discharged after being managed, and 89% were transferred to different wards. The intra-emergency centre mortality rate was 11.8% among admitted patients in the ER at Beni General Referral Hospital. Conclusion: This epidemiology database underlines the need for developing globalizing and multi-sectoral interventions (diagnosis, therapeutic strategy, organization, health program, or health policies) in the perspective of bringing change and/or taking action in the Democratic Republic of Congo's emergency medical system.

A novel method for the simultaneous assessment of natural killer cell conjugate formation and cytotoxicity at the single-cell level by multi-parameter flow cytometry.

A flow cytometric assay for the combined measurement of cell-mediated cytotoxicity and conjugate formation has been developed. Cytolysis is detected by propidium iodide uptake. Target cells, effector cells and conjugates between targets and effectors are separated by post-culture immunophenotyping and their scatter profiles. Pre-assay staining of cells is thus not required. Each cluster of cells can be further examined at the single-cell level by simultaneously performed additional immunophenotyping. Two applications were established: the assessment of NK cell activity against K562 cells and the evaluation of LAK cell cytotoxicity against both K562 and Daudi cells. A comparison with the standard 51Cr release assay for the detection of NK cytotoxicity showed that the two assays were strongly correlated, but the sensitivity of the flow cytometric assay was significantly higher.

Effects of electrode configuration and place of stimulation on speech perception with cochlear prostheses.

Recent research and clinical experience with cochlear implants suggest that subjects' speech recognition with monopolar or broad bipolar stimulation might be equal to or better than that obtained with narrow bipolar stimulation or other spatially restricted electrode configurations. Furthermore, subjects often prefer the monopolar configurations. The mechanisms underlying these effects are not clear. Two hypotheses are (a) that broader configurations excite more neurons resulting in a more detailed and robust neural representation of the signal and (b) that broader configurations achieve a better spatial distribution of the excited neurons. In this study we compared the effects of electrode configuration and the effects of longitudinal placement and spacing of the active electrodes on speech recognition in human subjects. We used experimental processor maps consisting of 11 active electrodes in a 22-electrode scala tympani array. Narrow bipolar (BP), wide bipolar (BP + 6), and monopolar (MP2) configurations were tested with various locations of active electrodes. We tested basal, centered, and apical locations (with adjacent active electrodes) and spatially distributed locations (with every other electrode active) with electrode configuration held constant. Ten postlingually deafened adult human subjects with Nucleus prostheses were tested using the SPEAK processing strategy. The effects of electrode configuration and longitudinal place of stimulation on recognition of CNC phonemes and words in quiet and CUNY sentences in noise (+10 dB S/N) were similar. Both independent variables had large effects on speech recognition and there were interactions between these variables. These results suggest that the effects of electrode configuration on speech recognition might be due, in part, to differences among the various configurations in the spatial location of stimulation. Correlations of subjective judgments of sound quality with speech-recognition ability were moderate, suggesting that the mechanisms contributing to subjective quality and speech-recognition ability do not completely overlap.

KINI: a one compartment intravenous pharmacokinetic analysis program.

KINI is a microcomputer PC based software package which determines the one-compartment pharmacokinetic parameters for any drug using the Sawchuk-Zaske method. Through use of these programs, individualized pharmacokinetic analyses can be performed. The package allows for analysis of adult and pediatric patients, as well as offering a long and abbreviated data entry format. Additionally, KINI can generate a data file to be used with WordPerfect 5.0 or 5.1 to produce a consult for chart use.

Kinetic analyses of plant water relocation using deuterium as tracer - reduced water flux of Arabidopsis pip2 aquaporin knockout mutants.

Due to reduced evaporation and diffusion of water molecules containing heavier isotopes, leaf water possesses an elevated (18)O or (2)H steady-state content. This enrichment has been exploited in plant physiology and ecology to assess transpiration and leaf water relations. In contrast to these studies, in this work the (2)H content of the medium of hydroponically grown Arabidopsis thaliana was artificially raised, and the kinetics of (2)H increase in the aerial parts recorded during a short phase of 6-8 h, until a new equilibrium at a higher level was reached. A basic version of the enrichment models was modified to establish an equation that could be fitted to measured leaf (2)H content during uptake kinetics. The fitting parameters allowed estimation of the relative water flux q(leaf) into the Arabidopsis rosette. This approach is quasi-non-invasive, since plants are not manipulated during the uptake process, and therefore, offers a new tool for integrated analysis of plant water relations. The deuterium tracer method was employed to assess water relocation in Arabidopsis pip2;1 and pip2;2 aquaporin knockout plants. In both cases, q(leaf) was significantly reduced by about 20%. The organ and cellular expression patterns of both genes imply that changes in root hydraulic conductivity, as previously demonstrated for pip2;2 mutants, and leaf water uptake and distribution contributed in an integrated fashion to this reduced flux in intact plants.

Monitoring great ape and elephant abundance at large spatial scales: measuring effectiveness of a conservation landscape.

Protected areas are fundamental to biodiversity conservation, but there is growing recognition of the need to extend beyond protected areas to meet the ecological requirements of species at larger scales. Landscape-scale conservation requires an evaluation of management impact on biodiversity under different land-use strategies; this is challenging and there exist few empirical studies. In a conservation landscape in northern Republic of Congo we demonstrate the application of a large-scale monitoring program designed to evaluate the impact of conservation interventions on three globally threatened species: western gorillas, chimpanzees and forest elephants, under three land-use types: integral protection, commercial logging, and community-based natural resource management. We applied distance-sampling methods to examine species abundance across different land-use types under varying degrees of management and human disturbance. We found no clear trends in abundance between land-use types. However, units with interventions designed to reduce poaching and protect habitats--irrespective of land-use type--harboured all three species at consistently higher abundance than a neighbouring logging concession undergoing no wildlife management. We applied Generalized-Additive Models to evaluate a priori predictions of species response to different landscape processes. Our results indicate that, given adequate protection from poaching, elephants and gorillas can profit from herbaceous vegetation in recently logged forests and maintain access to ecologically important resources located outside of protected areas. However, proximity to the single integrally protected area in the landscape maintained an overriding positive influence on elephant abundance, and logging roads--even subject to anti-poaching controls--were exploited by elephant poachers and had a major negative influence on elephant distribution. Chimpanzees show a clear preference for unlogged or more mature forests and human disturbance had a negative influence on chimpanzee abundance, in spite of anti-poaching interventions. We caution against the pitfalls of missing and confounded co-variables in model-based estimation approaches and highlight the importance of spatial scale in the response of different species to landscape processes. We stress the importance of a stratified design-based approach to monitoring species status in response to conservation interventions and advocate a holistic framework for landscape-scale monitoring that includes smaller-scale targeted research and punctual assessment of threats.

Estimation of psychophysical levels using the electrically evoked compound action potential measured with the neural response telemetry capabilities of Cochlear Corporation's CI24M device.

OBJECTIVE: The goal of this study was to estimate psychophysical levels using the electrically evoked compound action potential (EAP), measured with the Neural Response Telemetry capabilities of Cochlear Corporation's Nucleus CI24M cochlear implant system. DESIGN: Twelve postlingually deafened adults with at least 3 mo of implant experience with the CI24M were subjects in this study. EAP growth functions were successfully quantified on each active electrode of every subject. Correlation and regression analyses were performed between EAP measures and cochlear implant fitting psychophysics. Other information including performance, etiology and duration of hearing loss, and individual electrode impedance was considered. RESULTS: EAP thresholds were found to be highly correlated with psychophysical thresholds. The rate of EAP growth with increasing stimulation levels was also found to be correlated with the dynamic range of loudness limits and psychophysical thresholds in some subjects. No relationship was evident between EAP measures and speech perception tests. CONCLUSIONS: Information from EAP growth function measurements may be used to estimate psychophysical information used in cochlear implant fitting but not to predict performance with the device.

Cumulative dose response study comparing clinical effects of two doses of terbutaline sulphate administered via a 750 ml spacer to asthmatic patients.

Thirteen out-patients suffering from chronic reversible bronchial obstruction were treated on two separate days with two doses of terbutaline aerosol, administered with a 750 ml spacer interposed between the actuator and the mouth, in order to evaluate whether clinical responses showed a dose dependency during a 4-h period. On each day the two different doses (65 micrograms versus 250 micrograms) were inhaled three times at 15-min intervals. Fifteen minutes after the first dose there was a significant difference in FEV1 increase between the small dose and the normal dose, FEV1 being higher after 250 micrograms, but no significant differences in increase after the 2nd and 3rd inhalations. This study indicates that the bronchodilating effect of terbutaline administered via the spacer is dose-dependent at the first inhalation, and that succeeding inhalations show no dose-response effects.

Effects of acoustic trauma on the representation of the vowel "eh" in cat auditory nerve fibers.

A population study of cat auditory-nerve fibers was used to characterize the permanent deficits induced by exposure to 110-115 dB SPL, narrow-band noise. Fibers in the region of acoustic trauma (roughly 1-6 kHz) showed a loss of sensitivity at best frequency (BF) of about 50-60 dB and an increased tuning bandwidth. A correlation between weakened two-tone suppression and loss of sensitivity was found for fibers with BFs above 1 kHz. Single-fiber responses to the vowel "eh" were recorded at intensities ranging from near threshold to a maximum of about 110 dB SPL. In normal cochleas, the temporal response patterns show a capture phenomenon, in which the first two formant frequencies dominate the responses at high sound levels among fibers with BFs near the formant frequencies. After acoustic trauma, fibers in the region of threshold shift synchronized to a broad range of the vowel's harmonics and thus did not show capture by the second formant at any sound level used. The broadband nature of this response is consistent with the broadened tuning observed in the damaged fibers, but may also reflect a weakening of compressive nonlinearities responsible for synchrony capture in the normal cochlea.

Incidence of and significant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring.

Incidence of and risk factors for aminoglycoside-associated nephrotoxicity (AAN) were evaluated in 1489 patients prospectively monitored with individualized pharmacokinetic monitoring (IPM). Incidence of AAN was 7.9% with individual (univariate) risk factors including advanced age, decreased albumin, poor nutritional status, pneumonia, concurrent furosemide, amphotericin B, vancomycin, cephalosporin, or piperacillin, intensive care unit treatment, leukemia, rapidly fatal illness, liver or renal disease, reduced aminoglycoside clearance, elevated initial steady-state trough concentration (Cminss), volume of distribution or half-life, duration of therapy, total dose, fever, male gender, shock, pleural effusion, and ascites. Multiple logistic regression revealed that Cminss, concurrent clindamycin, vancomycin, piperacillin, or cephalosporin, ascites, advanced age, male gender, decreased albumin, duration of therapy, and leukemia were significant independent risk factors for AAN. Positive predictive value of the model was 30.8%; negative predictive value was 91.7%. No identifiable risk factor alone or in combination was of sufficient sensitivity to reliably predict AAN, but use of IPM may lower the incidence of AAN.

Interferometer-controlled scanning transmission X-ray microscopes at the Advanced Light Source.

Two new soft X-ray scanning transmission microscopes located at the Advanced Light Source (ALS) have been designed, built and commissioned. Interferometer control implemented in both microscopes allows the precise measurement of the transverse position of the zone plate relative to the sample. Long-term positional stability and compensation for transverse displacement during translations of the zone plate have been achieved. The interferometer also provides low-distortion orthogonal x, y imaging. Two different control systems have been developed: a digital control system using standard VXI components at beamline 7.0, and a custom feedback system based on PC AT boards at beamline 5.3.2. Both microscopes are diffraction limited with the resolution set by the quality of the zone plates. Periodic features with 30 nm half period can be resolved with a zone plate that has a 40 nm outermost zone width. One microscope is operating at an undulator beamline (7.0), while the other is operating at a novel dedicated bending-magnet beamline (5.3.2), which is designed specifically to illuminate the microscope. The undulator beamline provides count rates of the order of tens of MHz at high-energy resolution with photon energies of up to about 1000 eV. Although the brightness of a bending-magnet source is about four orders of magnitude smaller than that of an undulator source, photon statistics limited operation with intensities in excess of 3 MHz has been achieved at high energy resolution and high spatial resolution. The design and performance of these microscopes are described.

Development of scanning X-ray microscopes for materials science spectromicroscopy at the Advanced Light Source.

The development of two zone-plate microscopes for X-ray spectroscopic analysis of materials is described. This pair of instruments will provide imaging NEXAFS analysis of samples in transmission at atmospheric pressure and imaging XPS and NEXAFS analysis of sample surfaces in a UHV environment.