Minute-of-Arc Resolution Gamma ray Imaging Experiment—MARGIE

MARGIE (Minute-of-Arc Resolution Gamma-ray Imaging Experiment) is a large area(∼104 cm2), wide field-of-view (∼1 sr), hard X-ray/gamma-ray (∼20–600 keV) coded-mask imaging telescope capable of performing a sensitive survey of both steady and transient cosmic sources. MARGIE has been selected for a NASA mission-concept study for an Ultra Long Duration (100 day) Balloon flight. We describe our program to develop the instrument based on new detector technology of either cadmium zinc telluride (CZT) semiconductors or pixellated cesium iodide (CsI) scintillators viewed by fast-timing bi-directional charge-coupled devices (CCDs). The primary scientific objectives are to image faint Gamma-Ray Bursts (GRBs) in near-real-time at the low intensity (high-redshift) end of the logN-logS distribution, thereby extending the sensitivity of present observations, and to perform a wide field survey of the Galactic plane

MARGIE: A gamma-ray burst ultra-long duration balloon mission

We are designing MARGIE as a 100 day ULDB mission to: a) detect and localize gamma-ray bursts; and b) survey the hard X-ray sky. MARGIE will consist of one small field-of-view (FOV) and four large FOV coded mask modules mounted on a balloon gondola. The burst position will be calculated onboard and disseminated in near-real time, while information about every count will be telemetered to the ground for further analysis. In a 100-day mission we will localize ∼40 bursts with peak photon fluxes from 0.14 to ∼5 ph cm−2 s−1 using 1 s integrations; the typical localization resolution will be better than ∼2 arcminutes

Intravascular ultrasound scanning improves long-term patency of iliac lesions treated with balloon angioplasty and primary stenting

AbstractPurpose: Underdeployment of an intravascular stent has been identified as a cause of restenosis or occlusion of a treated arterial lesion. Intravascular ultrasound (IVUS) has been shown to initially improve the anatomic and clinical stenting. The purpose of this study was to determine whether the use of IVUS increased long-term patency of this intervention. Methods: Between March 1992 and October 1995, 71 limbs (52 patients) with symptomatic aortoiliac occlusive disease underwent balloon angioplasty with primary stenting. IVUS and arteriography were used in 49 limbs (36 patients) to evaluate stent deployment. Arteriography alone was used in 22 limbs (16 patients) to evaluate stent deployment. Patients were captured prospectively in a vascular registry and retrospectively reviewed. Results: Mean age of patients treated with IVUS was 61.1 ± 9.0 years (range, 38-85) versus 70.0 ± 10.1 years (range, 57-87) in patients treated without IVUS (P <.01). There was no difference between the groups with respect to preoperative comorbidities, ankle-brachial indices, or number of stents per limb. Mean follow-up for IVUS patients was 62.1 ± 7.3 months (range, 15-81) and 57.9 ± 8.7 months (range, 8-80) for patients treated without IVUS (P = not significant). In 40% (20/49) of limbs, IVUS demonstrated inadequate stent deployment at the time of the original procedure. Kaplan-Meier 3- and 6-year primary patency estimates were 100% and 100% in the IVUS group and 82% and 69%, respectively, in limbs treated without IVUS (P <.001). There have been no secondary procedures performed in limbs treated with IVUS and a 23% (5/22) secondary intervention rate in the non-IVUS group (P <.05). Overall Kaplan-Meier survival estimates at 3 and 6 years for all patients were 84% and 67%, respectively. Conclusion: Balloon angioplasty and primary stenting of symptomatic aortoiliac occlusive lesions is a durable treatment option. Long-term follow-up of treated patients shows outcomes that are comparable with direct surgical intervention. IVUS significantly improved the long-term patency of iliac arterial lesions treated with balloon angioplasty and stenting by defining the appropriate angioplasty diameter endpoint and adequacy of stent deployment. (J Vasc Surg 2002;35:316-23.

The Developmental Trajectories of Children’s Reorientation to Global and Local Properties of Environmental Geometry

The way in which organisms represent the shape of their environments during navigation has been debated in cognitive, comparative, and developmental psychology. While there is evidence that adult humans encode the entire boundary shape of an environment (a global-shape representation), there are also data demonstrating that organisms reorient using only segments of the boundary that signal a goal location (a local-shape representation). Developmental studies offer unique insights into this debate; however, most studies have used designs that cannot dissociate the type of boundary-shape representation that children use to guide reorientation. Thus, we examined the developmental trajectories of children’s reorientation according to local and global boundary shape. Participants aged 6–12 years were trained to find a goal hidden in one corner of a virtual arena, after which they were required to reorient in a novel test arena. From 10.5 years, children performed above chance when the test arena permitted reorientation based only on local-shape (Experiment 2), or only global-shape (Experiment 3) information. Moreover, when these responses were placed into conflict, older children reoriented with respect to global-shape information (Experiment 4). These age-related findings were not due to older children being better able to reorient in virtual environments per se: when trained and tested within the same environment (Experiment 1), children performed above chance from 6 years. Together, our results suggest (a) the ability to reorient on the basis of global and local-shape representations develops in parallel, and (b) shape-based information is weighted to determine which representation informs reorientatio

Novel pathogenic COX20 variants causing dysarthria, ataxia, and sensory neuropathy.

COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron-one (c.41A&gt;G), while the other variant (c.157+3G&gt;C) affected the splice donor site of intron-two. cDNA and protein analysis indicated that no full-length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency

Leptin modifies the prosecretory and prokinetic effects of the inflammatory cytokine interleukin-6 on colonic function in Sprague–Dawley rats

Leptin ameliorates the prosecretory and prokinetic effects of the pro-inflammatory cytokine interleukin-6 on rat colon. Leptin also suppresses the neurostimulatory effects of irritable bowel syndrome plasma, which has elevated concentrations of interleukin-6, on enteric neurons. This may indicate a regulatory role for leptin in immune-mediated bowel dysfunction. In addition to its role in regulating energy homeostasis, the adipokine leptin modifies gastrointestinal (GI) function. Indeed, leptin-resistant obese humans and leptin-deficient obese mice exhibit altered GI motility. In the functional GI disorder irritable bowel syndrome (IBS), circulating leptin concentrations are reported to differ from those of healthy control subjects. Additionally, IBS patients display altered cytokine profiles, including elevated circulating concentrations of the pro-inflammatory cytokine interleukin-6 (IL-6), which bears structural homology and similarities in intracellular signalling to leptin. This study aimed to investigate interactions between leptin and IL-6 in colonic neurons and their possible contribution to IBS pathophysiology. The functional effects of leptin and IL-6 on colonic contractility and absorptosecretory function were assessed in organ baths and Ussing chambers in Sprague–Dawley rat colon. Calcium imaging and immunohistochemical techniques were used to investigate the neural regulation of GI function by these signalling molecules. Our findings provide a neuromodulatory role for leptin in submucosal neurons, where it inhibited the stimulatory effects of IL-6. Functionally, this translated to suppression of IL-6-evoked potentiation of veratridine-induced secretory currents. Leptin also attenuated IL-6-induced colonic contractions, although it had little direct effect on myenteric neurons. Calcium responses evoked by IBS plasma in both myenteric and submucosal neurons were also suppressed by leptin, possibly through interactions with IL-6, which is elevated in IBS plasma. As leptin has the capacity to ameliorate the neurostimulatory effects of soluble mediators in IBS plasma and modulated IL-6-evoked changes in bowel function, leptin may have a role in immune-mediated bowel dysfunction in IBS patients

Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation

Previous studies have shown that exogenous ATP (>1µM) prevents bone formation in vitro by blocking mineralisation of the collagenous matrix. This effect is thought to be mediated via both P2 receptor-dependent pathways and a receptor-independent mechanism (hydrolysis of ATP to produce the mineralisation inhibitor pyrophosphate, PPi). Osteoblasts are also known to release ATP constitutively. To determine whether this endogenous ATP might exert significant biological effects, bone-forming primary rat osteoblasts were cultured with 0.5-2.5U/ml apyrase (which sequentially hydrolyses ATP to ADP to AMP + 2Pi). Addition of 0.5U/ml apyrase to osteoblast culture medium degraded extracellular ATP to <1% of control levels within 2 minutes; continuous exposure to apyrase maintained this inhibition for up to 14 days. Apyrase treatment for the first 72 hours of culture caused small decreases (≤25%) in osteoblast number, suggesting a role for endogenous ATP in stimulating cell proliferation. Continuous apyrase treatment for 14 days (≥0.5U/ml) increased mineralisation of bone nodules by up to 3-fold. Increases in bone mineralisation were also seen when osteoblasts were cultured with the ATP release inhibitors, NEM and brefeldin A, as well as with P2X1 and P2X7 receptor antagonists. Apyrase decreased alkaline phosphatase (TNAP) activity by up to 60%, whilst increasing the activity of the PPi-generating ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) up to 2.7-fold. Both collagen production and adipocyte formation were unaffected. These data suggest that nucleotides released by osteoblasts in bone could act locally, via multiple mechanisms, to limit mineralisation

Beam test results for the FiberGLAST instrument

The FiberGLAST scintillating fiber telescope is a large-area instrument concept for NASA\u27s GLAST program. The detector is designed for high-energy gamma-ray astronomy, and uses plastic scintillating fibers to combine a photon pair tracking telescope and a calorimeter into a single instrument. A small prototype detector has been tested with high energy photons at the Thomas Jefferson National Accelerator Facility. We report on the result of this beam test, including scintillating fiber performance, photon track reconstruction, angular resolution, and detector efficiency

Development and testing of a fiber/multianode photomultiplier system for use on FiberGLAST

A scintillating fiber detector is currently being studied for the NASA Gamma-Ray Large Area Space Telescope (GLAST) mission. This detector utilizes modules composed of a thin converter sheet followed by an x, y plane of scintillating fibers to examine the shower of particles created by high energy gamma-rays interacting in the converter material. The detector is composed of a tracker with 90 such modular planes and a calorimeter with 36 planes. The two major component of this detector are the scintillating fibers and their associated photodetectors. Here we present current status of development and test result of both of these. The Hamamatsu R5900-00-M64 multianode photomultiplier tube (MAPMT) is the baseline readout device. A characterization of this device has been performed including noise, cross- talk, gain variation, vibration, and thermal/vacuum test. A prototype fiber/MAPMT system has been tested at the Center for Advanced Microstructures and Devices at Louisiana State University with a photon beam and preliminary results are presented