A field programmable gate array based Langmuir probe system for measurement of plasma parameters at 500 kHz in a high-power impulse magnetron sputtering plasma.

By utilizing Field Programmable Gate Arrays in a configuration similar to that of the Mirror Langmuir Probe, it is possible to bias a single probe at three precise voltages in sequence. These voltages can be dynamically adjusted in real-time based on the measured plasma electron temperature to ensure the transition region is always sampled. The first results have been obtained by employing this method and have generated real-time outputs of electron temperature, ion saturation current, and floating potential on a low temperature pulsed-DC magnetron at 500 kHz. These results are in good agreement with the analysis of a conventionally swept Langmuir probe. This probe is designed with the intention of being implemented on MAST-U to aid in the study of exhaust physics and enable further investigation into filamentary behavior.

Overview of the Langmuir probe system on the Mega Ampere Spherical Tokamak (MAST) Upgrade.

A detailed description of the Langmuir probe system on Mega Ampere Spherical Tokamak Upgrade is presented. The system features 850 tile-embedded probes and 40 bespoke electronic modules that each have the capability to drive and acquire data from up to 16 probes in a time-multiplexed manner. The system provides spatiotemporal-resolved measurements (1 cm and ∼1 ms, respectively) in the divertor region of ion saturation current, electron temperature, and floating potential. The standard interpretation of current-voltage (IV) characteristics is to apply a four-parameter fit, based on unmagnetized probe theory, which includes a linear model for the ion saturation region. To mitigate the effect of the magnetic field, analysis is restricted to the region of the IV characteristic, which is sensitive to only the tail of the electron energy distribution function.

2D measurements of plasma electron density using coherence imaging with a pixelated phase mask.

In this paper, the pixelated phase mask (PPM) method of interferometry is applied to coherence imaging (CI)-a passive, narrowband spectral imaging technique for diagnosing the edge and divertor regions of fusion plasma experiments. Compared to previous CI designs that use a linear phase mask, the PPM method allows for a higher possible spatial resolution. The PPM method is also observed to give a higher instrument contrast (analogous to a more narrow spectrometer instrument function). A single-delay PPM instrument is introduced as well as a multi-delay system that uses a combination of both pixelated and linear phase masks to encode the coherence of the observed radiation at four different interferometer delays simultaneously. The new methods are demonstrated with measurements of electron density ne, via Stark broadening of the Hγ emission line at 434.0 nm, made on the Magnum-PSI linear plasma experiment. A comparison of the Abel-inverted multi-delay CI measurements with Thomson scattering shows agreement across the 3 × 1019 < ne < 1 × 1021 m-3 range. For the single-delay CI results, agreement is found for ne > 1 × 1020 m-3 only. Accurate and independent interpretation of single-delay CI data at lower ne was not possible due to Doppler broadening and continuum emission.

Development of an 11-channel multi wavelength imaging diagnostic for divertor plasmas in MAST Upgrade.

Divertor detachment and alternative divertor magnetic geometries are predicted to be promising approaches to handle the power exhaust of future fusion devices. In order to understand the detachment process caused by volumetric losses in alternative divertor magnetic geometries, a Multi-Wavelength Imaging (MWI) diagnostic has recently been designed and built for the Mega Amp Spherical Tokamak Upgrade. The MWI diagnostic will simultaneously capture 11 spectrally filtered images of the visible light emitted from divertor plasmas and provide crucial knowledge for the interpretation of observations and modeling efforts. This paper presents the optical design, mechanical design, hardware, and test results of an 11-channel MWI system with a field of view of 40°. The optical design shows better than 5 mm FWHM spatial resolution at the plasma on all 11 channels across the whole field of view. The spread of angle of incidence on the surface of each filter is also analyzed to inform the bandwidth specification of the interference filters. The results of the initial laboratory tests demonstrate that a spatial resolution of better than 5 mm FWHM is achieved for all 11 channels, meeting the specifications required for accurate tomography.

Physically principled reflection models applied to filtered camera imaging inversions in metal walled fusion machines.

Ray-tracing techniques are applied to filtered divertor imaging, a diagnostic that has long suffered from artifacts due to the polluting effect of reflected light in metal walled fusion machines. Physically realistic surface reflections were modeled using a Cook-Torrance micro-facet bi-directional reflection distribution function applied to a high resolution mesh of the vessel geometry. In the absence of gonioreflectometer measurements, a technique was developed to fit the free parameters of the Cook-Torrance model against images of the JET in-vessel light sources. By coupling this model with high fidelity plasma fluid simulations, photo-realistic renderings of a number of tokamak plasma emission scenarios were generated. Finally, a sensitivity matrix describing the optical coupling of a JET divertor camera and the emission profile of the plasma was obtained, including full reflection effects. These matrices are used to perform inversions on measured data and shown to reduce the level of artifacts in inverted emission profiles.

MANTIS: A real-time quantitative multispectral imaging system for fusion plasmas.

This work presents a novel, real-time capable, 10-channel Multispectral Advanced Narrowband Tokamak Imaging System installed on the TCV tokamak, MANTIS. Software and hardware requirements are presented together with the complete system architecture. The image quality of the system is assessed with emphasis on effects resulting from the narrowband interference filters. Some filters are found to create internal reflection images that are correlated with the filters' reflection coefficient. This was measured for selected filters where significant absorption (up to 65% within ∼70 nm of the filter center) was measured. The majority of this was attributed to the filter's design, and several filters' performance is compared. Tailored real-time algorithms exploiting the system's capabilities are presented together with benchmarks comparing polling and event based synchronization. The real-time performance is demonstrated with a density ramp discharge performed on TCV. The behavior of spectral lines' emission from different plasma species and their interpretation are qualitatively described.

The multi-spectral imaging diagnostic.

The Multi-Spectral Imaging system is a new diagnostic that captures simultaneous spectrally filtered images from a common line of sight while maintaining a large étendue and high throughput. Imaging several atomic line intensities simultaneously may enable numerous measurement techniques. By making a novel modification of a polychromator layout, the MSI sequentially filters and focuses images onto commercial CMOS cameras while exhibiting minimal vignetting and aberrations. A four-wavelength system was initially installed and tested on Alcator C-Mod and subsequently moved to TCV. The images are absolutely calibrated and spatially registered enabling 2D mappings of atomic line ratios and absolute line intensities. The spectral transmission of the optical system was calibrated using an integrating sphere of known radiance. The images are inverted by cross-referencing points on TCV with a computer-aided design (CAD) model.

Coherence imaging of scrape-off-layer and divertor impurity flows in the Mega Amp Spherical Tokamak (invited).

A new coherence imaging Doppler spectroscopy diagnostic has been deployed on the UK's Mega Amp Spherical Tokamak for scrape-off-layer and divertor impurity flow measurements. The system has successfully obtained 2D images of C III, C II, and He II line-of-sight flows, in both the lower divertor and main scrape-off-layer. Flow imaging has been obtained at frame rates up to 1 kHz, with flow resolution of around 1 km/s and spatial resolution better than 1 cm, over a 40° field of view. C III data have been tomographically inverted to obtain poloidal profiles of the parallel impurity flow in the divertor under various conditions. In this paper we present the details of the instrument design, operation, calibration, and data analysis as well as a selection of flow imaging results which demonstrate the diagnostic's capabilities.

Divertor impurity injection using high voltage arcs for impurity transport studies on the Mega Amp Spherical Tokamak.

The operation of next-generation fusion reactors will be significantly affected by impurity transport in the scrape-off layer (SOL). Current modelling efforts are restricted by a lack of detailed data on impurity transport in the SOL. In order to address this, a carbon injector has been designed and installed on the Mega Amp Spherical Tokamak (MAST). The injector creates short lived carbon plumes originating at the MAST divertor lasting less than 50 µs. High voltage capacitor banks are used to create a discharge across concentric carbon electrodes located in a probe mounted on the Divertor Science Facility in the MAST lower divertor. This results in a very short plume duration allowing observation of the evolution of the plume and precise localisation of the plume relative to the X-point on MAST. The emission from the carbon plume was imaged using fast visible cameras filtered in order to isolate the carbon II and carbon III emission lines centered around 514 nm and 465 nm.

Impaired cortical bone acquisition and osteoblast differentiation in mice with osteoblast-targeted disruption of glucocorticoid signaling.

To determine the role of endogenous glucocorticoids in bone, we previously developed transgenic mice in which a 2.3 kb fragment of the Col1a1 promoter drives 11beta-hydroxysteroid dehydrogenase 2 expression in mature osteoblasts. This transgene should inactivate glucocorticoids upstream of all receptor signaling pathways. In the present study, we show that femoral cortical bone area and thickness were approximately 10-15% lower in transgenic mice than in wild-type littermates. Femur length was unchanged, indicating that bone elongation was not affected in this model. Expression of osteocalcin mRNA, pOBCol2.3-GFP (a green fluorescent protein marker of mature osteoblasts), and the formation of mineralized nodules were impaired in ex vivo transgenic primary calvarial cultures. The extent of crystal violet staining in bone marrow cultures, indicative of the number of adherent stromal cells, was also decreased. These data suggest that endogenous glucocorticoids are required for cortical bone acquisition and full osteoblast differentiation. It appears that blocking glucocorticoid signaling in vivo leads to a decrease in the commitment and/or expansion of progenitors entering the osteoblast lineage.

Mandibular phenotype of p20C/EBPbeta transgenic mice: Reduced alveolar bone mass and site-specific dentin dysplasia.

CCAAT enhancer binding proteins (C/EBP) comprise a family of basic-leucine zipper transcription factors that regulate cellular differentiation and function. To determine the role of C/EBP transcription factors in osteoblasts and odontoblasts, we generated a transgenic (TG) mouse model with Co1a1 (pOBCol3.6) promoter-targeted expression of a FLAG-tagged dominant negative C/EBP isoform, p20C/EBPbeta (previously LIP). Two of the four transgenic lines presented with abnormalities in the developing incisors, including breakage, overgrowth, and malocclusion. Histological examination revealed that the amount of alveolar bone was reduced in TG compared to wild-type (WT) mice. By microcomputed tomography (microCT), the bone volume fraction of the mandible was reduced at the level of the first and third molars, demonstrating a severe mandibular osteopenia. The lingual dentin morphology of TG incisors differed dramatically from WT. Labial dentin (enamel side) showed normal thickness and tubular dentin structure, whereas the lingual dentin was thinner (25-30% of WT at the alveolar crest) with an amorphous globular structure characteristic of dentin dysplasia. FLAG immunostaining was seen in both lingual and labial odontoblasts, indicating that the site-specific defect was not due to a lack of labial transgene expression. Northern blot analysis demonstrated reduced osteocalcin expression in TG mandibles, while bone sialoprotein was increased, consistent with prior results in calvariae and long bones. Dental sialophosphoprotein, a marker of the odontoblast lineage whose absence causes dentin dysplasia, was modestly reduced in TG mice by Northern blot and in situ hybridization analysis. By fluorescence microscopy, pOBCol2.3-GFP, a marker of the odontoblast lineage, was expressed in both labial and lingual odontoblasts, although GFP-marked lingual odontoblasts were more flattened than WT cells. Moreover, GFP-positive processes in the lingual dentin tubules were truncated and less organized than those in WT dentin. MicroCT analysis showed reduced tissue density in the lingual dentin. These data suggest that C/EBP transcription factors may be involved in the regulation of odontoblast polarization and dentin matrix production.

Ill-health retirement: national rates and updated guidance for occupational physicians.

BACKGROUND: Advising on ill-health retirement is an important role of most practising occupational physicians. In recent years, the eligibility criteria and process for gaining early retirement benefits have changed in many pension schemes in the UK. AIM: To investigate the variation in rates of retirement due to ill-health in National Health Service (NHS) Trusts and Local Authorities and to update previously published guidance on ill-health retirement with specific reference to pension schemes with eligibility criteria that include permanence of incapacity due to ill-health. METHODS: Rates of retirement were calculated for 222 NHS Trusts and 132 Local Authorities with more than 1500 employees. Literature searches and consensus statements by the authors. RESULTS: Rates of retirement were widely distributed in the NHS Trusts and Local Authorities. The median rates of retirement were 2.11 (IQR 1.37-2.91)/1000 active members and 4.10 (IQR 3.01-6.10)/1000 employees, respectively (P<0.001). Difficulties in the doctor-patient relationship and in ascertaining the true functional ability of some patients were identified. CONCLUSION: There continues to be marked variation in rates of early retirement due to ill-health within and between organizations that warrants further investigation. The general and specific guidance that appears as an appendix in Supplementary data to this paper should help occupational physicians to make equitable recommendations when assessing applications for early retirement benefits and fitness to work.

Urine amino and organic acids analysis in developmental delay or intellectual disability.

OBJECTIVES: To determine the proportion of urine amino and organic acids screening tests (UMS) undertaken for patients referred with developmental delay or intellectual disability (DD/ID), and within the group with DD/ID, to determine the diagnostic yield, the proportion of diagnoses with a therapy and the associated recurrence risks. METHODS: A retrospective review of request forms and results of UMS, in individuals older than 28 days, referred to the Women's and Children's Hospital, North Adelaide, between 1 January 1992 and 31 December 1998 was carried out. Urine was analysed by ion exchange chromatography (amino acids), gas chromatography/mass spectrometry (organic acids), colorimetric assay (orotic acid) and stable isotope-dilution mass spectrometry (trimethylamine). RESULTS: A total of 3316 samples were received, 1447 being from patients with DD/ID. A diagnosis was determined for 1.8% of all referrals. For patients with DD/ID, the diagnostic yield was 1.1%, with a similar yield for isolated DD/ID and DD/ID with other features (9/828 vs 7/619; chi2 = 0.006; P = 0.93). Specific therapies were available for 69% of diagnoses associated with DD/ID and 87.5% had known Mendelian or mitochondrial inheritance. CONCLUSION: Urine metabolic screening is an important part of the evaluation of children with DD/ID as it can enable families to make reproductive decisions and children to receive appropriate therapy early.

Gastro-oesophageal reflux disease in obesity: pathophysiological and therapeutic considerations.

Gastro-oesophageal reflux disease (GERD) is common in obese patients. Apart from the physical discomfort and the economic burden, GERD may increase morbidity and mortality through its association with oesophageal carcinoma. The pathophysiology of GERD differs between obese and lean subjects. First, obese subjects are more sensitive to the presence of acid in the oesophagus. Second, hiatal hernia, capable of promoting GERD by several mechanisms, is more prevalent among the obese. Third, obese subjects have increased intra-abdominal pressure that displaces the lower oesophageal sphincter and increases the gastro-oesophageal gradient. Finally, vagal abnormalities associated with obesity may cause a higher output of bile and pancreatic enzymes, which makes the refluxate more toxic to the oesophageal mucosa. The altered body composition associated with obesity affects the pharmacokinetics of drugs. There are no data regarding the efficacy of any of the drugs used for GERD treatment. The dosages of cimetidine and ranitidine should be calculated according to the patient's ideal body weight, not their actual weight. Of the operative procedures used for weight loss, Roux-en-Y gastric bypass was found to be most effective for GERD, while gastric banding was associated with a high prevalence of reflux. This review outlines the pathophysiology and the treatment of GERD in obesity with emphasis on the therapeutic considerations in this population of patients.

Chronic intermittent intestinal obstruction from a seat belt injury.

Most patients with intestinal obstruction have had previous surgery. Rarely, the development of adhesions and resulting small bowel obstruction is attributed to previous intra-abdominal trauma. We present the case of a young man, without a history of surgery, who had been a restrained driver in a motor vehicle crash. Seven years later, the patient had an intermittent partial small bowel obstruction that recurred over the next 5 years. We review the pathophysiology and epidemiology of similar occurrences, as well as diagnostic options.

Hepatic angiosarcoma: an unusual cause of congestive heart failure.

Hepatic angiosarcoma is a rare form of liver cancer. The history, physical examination, and liver biopsy are nonspecific. As a result, diagnosis of angiosarcoma can be challenging. We report the case of an elderly woman with congestive heart failure caused by a hepatic angiosarcoma. The massive tumor burden created extensive arteriovenous shunting and a high-cardiac-output state.

Involvement of CCAAT enhancer binding protein transcription factors in the regulation of prostaglandin G/H synthase 2 expression by interleukin-1 in osteoblastic MC3T3-E1 cells.

Interleukin-1 (IL-1) stimulates prostaglandin production in bone by a rapid and transient activation of prostaglandin G/H synthase 2 (PGHS-2) gene expression. In osteoblastic MC3T3-E1 cells, IL-1 caused a transient increase in PGHS-2 messenger RNA (mRNA), which peaked at 2 h. IL-1 caused a 2- to 4-fold activation of a 371-base pair (bp) murine PGHS-2 promoter/luciferase construct in stable transfectants. This response mapped to a proximal promoter element(s) located between -150 and -40 bp. This region contains a putative CCAAT enhancer binding protein (C/EBP) site (centered at -135 bp), which shows enhanced binding of C/EBPbeta and C/EBPdelta by mobility shift analysis after IL-1 treatment. A transient cotransfection approach was used to examine the effects of C/EBPbeta and C/EBPdelta overexpression. IL-1 caused a maximal 3- to 7-fold stimulation of PGHS-2 promoter activity after 2.5 h. Overexpression of murine C/EBPbeta and C/EBPdelta caused a dose-dependent increase in basal and IL-1-stimulated luciferase activity. C/EBPdelta caused a greater enhancement of basal and IL-1-stimulated promoter activity than C/EBPbeta, suggesting that C/EBPdelta is a stronger transactivator. Overexpression of p20C/EBPbeta, a dominant negative inhibitor of C/EBP function, blocked the stimulation of PGHS-2 promoter activity by IL-1 and blocked the ability of overexpressed C/EBPbeta and C/EBPdelta to increase basal and IL-1-stimulated promoter activity. Mutagenesis of the C/EBP site reduced, but did not abolish, the stimulation of PGHS-2 promoter activity by IL-1 and blunted the effect of overexpressed C/EBPdelta on basal and IL-1-stimulated promoter activity. These results suggest an essential role for C/EBPbeta and C/EBPdelta in the induction of PGHS-2 gene expression by IL-1 in osteoblastic cells.

Treatment of late-onset nonketotic hyperglycinaemia: effectiveness of imipramine and benzoate.

We report a patient with late-onset nonketotic hyperglycinaemia managed with a sequential approach to drug therapy in placebo-controlled therapeutic trials. Partial response to low-protein diet and sodium benzoate and dramatic response to imipramine are demonstrated, with parental scores on the Developmental Behavioural Checklist falling from the 86th centile before treatment to normal with combined benzoate and imipramine therapy.

Molecular modeling studies on G-quadruplex complexes of telomerase inhibitors: structure-activity relationships.

Inhibition of the ability of the enzyme telomerase to add telomeric repeats to the end of chromosomes is a novel target for potential anticancer therapy. This paper examines the hypothesis that compounds possessing a planar aromatic chromophore inhibit telomerase via stabilization of, and binding to, a folded guanine quadruplex structure. Two series of telomerase inhibitors have been designed based on the 2,6-disubstituted amidoanthracene-9,10-dione and 3,6-disubstituted acridine chromophores in order to investigate structure-activity relationships between biological activity and substituent group size. The relative binding energies between these compounds and the folded human telomere DNA quadruplex were determined using molecular simulation methods, involving explicitly solvated structures. The results obtained are in excellent agreement with the biological activity as measured in vitro using a modified TRAP assay and in general agreement with the ranking order of binding enthalpies found in isothermal titration calorimetry studies. This broad agreement provides strong support for the hypothesis that guanine quadruplexes are the primary target for telomerase inhibitors with extended planar chromophores.