Performance characteristics of a whole-body PET scanner

METHODS: This study characterizes the performance of a newly developed whole-body PET scanner (Advance, General Electric Medical Systems, Milwaukee, WI). The scanner consists of 12,096 bismuth germinate crystals (4.0 mm transaxial by 8.1 mm axial by 30 mm radial) in 18 rings, giving 35 two-dimensional image planes through an axial field of view of 15.2 cm. The rings are separated by retractable tungsten septa. Intrinsic spatial resolution, scatter fraction, sensitivity, high count rate performance and image quality are evaluated. RESULTS: Transaxial resolution (in FWHM) is 3.8 mm at the center and increases to 5.0 mm tangential and 7.3 mm radial at R = 20 cm. Average axial resolution decreases from 4.0 mm FWHM at the center to 6.6 mm at R = 20 cm. Scatter fraction is 9.4% and 10.2% for direct and cross slices, respectively. With septa out, the average scatter fraction is 34%. Total system sensitivity for true events (in kcps/(microCi/cc)) is 223 with septa in and 1200 with septa out. Dead-time losses of 50% correspond to a radioactivity concentration of 4.9 (0.81) microCi/cc and a true event count rate of 489 (480) kcps with septa in (out). Noise-equivalent count rate (NECR) for the system as a whole shows a maximum of 261 (159) kcps at a radioactivity concentration of 4.1 (0.65) microCi/cc with septa in (out). NECR is insensitive to changes in lower gamma-energy discrimination between 250-350 keV. CONCLUSIONS: The results show the performance of the newly designed PET scanner to be well suited for clinical and research applications.     

Distalless expression in crustaceans and the patterning of branched limbs

The ability of two-dimensional echocardiography to detect and to evaluate the extent of wall motion abnormalities is limited by the use of few selected, nonparallel, views of the whole left ventricle. This leads to an incomplete appreciation of the spatial relationships between various cardiac structures and inaccuracy in quantitative data as a result of using of geometric assumptions. Dynamic volume-rendered three-dimensional echocardiography has the ability to overcome the above limitations. In this article we review the use of volume-rendered three-dimensional echocardiography in the diagnosis and assessment of ischemic heart disease, including complications related to myocardial infarction.     

Melting of a DNA hairpin without hyperchromism

UV absorbance spectroscopy is the most common method for detecting nucleic acid structural transitions and obtaining thermodynamic parameters. UV-detected melting has been used to determine stabilities of nucleic acid hairpins, duplexes, triplexes, and higher order structures and to determine thermodynamic effects of unusual or modified bases and mismatched base-pairs. We report that in some cases UV absorbance spectroscopy is an inadequate analytical technique for these purposes. Some critical transitions are invisible to UV absorbance spectroscopy. For example, the conversion of dodecamer d(CGCAAATTCGCG) from hairpin to random coil is not accompanied by hyperchromism. Circular dichroism (CD) spectroscopy (263 nm) clearly detects two transitions for this dodecamer, each giving a pronounced change in ellipiticity. The concentration dependence of the low-temperature transition and the concentration independence of the high-temperature transition indicate that the predominant state converts from duplex to hairpin to random coil as the temperature increases. These assignments are confirmed by comparison to oligonucleotides of similar sequence that undergo a hairpin to coil transition only. In contrast to CD spectroscopy, UV absorbance spectroscopy shows only a single transition. The transition detected by UV absorbance spectroscopy corresponds to the low-temperature transition detected by CD. UV absorbance spectroscopy does not detect the second transition at any wavelength (from 218 to 310 nm) (by changes) in either absorbance or its derivative with temperature.     

Hyperphagia induced by hypoglycemia in rats is independent of leptin and hypothalamic neuropeptide Y (NPY)

Hypoglycemia causes hyperphagia and weight gain, through unknown peripheral and central signals. We investigated the effect of hypoglycemia on NPY and leptin expression and the ability of leptin to inhibit hypoglycemia-induced hyperphagia. Acute hypoglycemia (60 U/kg SC insulin; n = 8) increased food intake (p < 0.01) compared with controls (n = 8). Insulin- and leptin-treated rats (300 microg/kg IP leptin; n = 8) had reduced hyperphagia (p < 0.05 vs. controls; p < 0.05 vs. insulin alone) and a 15% fall in NPY mRNA levels compared with controls (p < 0.01). Chronic hypoglycemia, (20-60 U/kg/day insulin; n = 8) increased food intake compared with vehicle-treated controls (p < 0.01). Leptin and insulin administration (300 microg/kg/day IP leptin; n = 8) reduced hyperphagia (p < 0.01 vs. controls, p < 0.05 vs. insulin alone), and NPY mRNA fell by 18% vs. controls (p < 0.01). We conclude that hypoglycemia-induced hyperphagia is not mediated by either a fall in leptin or an increase in hypothalamic NPY mRNA. Leptin can inhibit feeding in hyperphagic hypoglycemic rats, and this may partly be attributable to its inhibition of the NPY neurons.     

Scanning alanine mutagenesis of the CDP-alcohol phosphotransferase motif of Saccharomyces cerevisiae cholinephosphotransferase

Cholinephosphotransferase (EC 2.7.8.2) catalyzes the formation of a phosphoester bond via the transfer of a phosphocholine moiety from CDP-choline to diacylglycerol forming phosphatidylcholine and releasing CMP. A motif, Asp113-Gly114-(X)2-Ala117-Arg118-(X)8-Gly127+ ++-(X)3-Asp131-(X)3-Asp135, located within the CDP-choline binding region of Saccharomyces cerevisiae cholinephosphotransferase (CPT1 ?/Author: Please confirm that a gene is meant here.) is also found in several other phospholipid synthesizing enzymes that catalyze the formation of a phosphoester bond utilizing a CDP-alcohol and a second alcohol as substrates. To determine if this motif is diagnostic of the above reaction type scanning alanine mutagenesis of the conserved residues within S. cerevisiae cholinephosphotransferase was performed. Enzyme activity was assessed in vitro using a mixed micelle enzyme assay and in vivo by determining the ability of the mutant enzymes to restore phosphatidylcholine synthesis from radiolabeled choline in an S. cerevisiae strain devoid of endogenous cholinephosphotransferase activity. Alanine mutants of Gly114, Gly127, Asp131, and Asp135 were inactive; mutants, Ala117 and Arg118 displayed reduced enzyme activity, and Asp113 displayed wild type activity. The analysis described is the first molecular characterization of a CDP-alcohol phosphotransferase motif and results predict a catalytic role utilizing a general base reaction proceeding through Asp131 or Asp135 via a direct nucleophilic attack of the hydroxyl of diacylglyerol on the phosphoester bond of CDP-choline that does not proceed via an enzyme bound intermediate. Residues Ala117 and Arg118 do not participate directly in catalysis but are likely involved in substrate binding or positioning with Arg118 predicted to associate with a phosphate moiety of CDP-choline.     

Down-regulation of glial fibrillary acidic protein expression during acute lytic varicella-zoster virus infection of cultured human astrocytes

The effects of the varicella-zoster virus (VZV) OKA vaccine strain in producing morphologic and antigenic changes in dissociated cultures of human fetal brain was investigated. Cultures containing 80% glial acidic fibrillary protein (GFAP), GFAP+ (positive) astrocytes and 20% GFAP- (negative) fibroblastic-like cells were infected with cell-free VZV OKA at a multiplicity of infection of 0.1 plaque-forming units per cell. Cytopathic effects and significant viral antigen labeling with antibodies against VZV gpl and immediate-early (IE) protein 62 were first detected 6 to 7 days postinfection. Several observations indicated that astrocyte GFAP expression was altered and diminished as a result of VZV infection itself, thereby raising doubts about the utility of combining cell markers and viral antigenic labeling in assessing the susceptibility of neural cell types to viral infection. The down-regulation of GFAP expression by VZV appears to be mediated by early rather than late events in the viral replication cycle and may not be the result of virally induced global shut-off of host cell protein synthesis. Similar observations were made using VZV Ellen, a multipassaged, nonvaccine strain. These observations have potential in vivo implications related to histologic analysis of VZV-infected tissues and disease pathogenesis.     

Targeting drug delivery and the small airways in asthma

A rare case of mycotic aneurysms of descending thoracic aorta is presented. A 63-year-old man was admitted with history of persistent high fever and loss of consciousness to our hospital. On admission, there were elevated WBC and CRP. Blood and spinal fluid cultures revealed growth of Streptococcus pneumonia. Despite of antibiotic therapy for meningitis and bacteremia, inflammatory sign continued, and new abnormal shadow appeared on chest X-ray. Chest CT and aortography showed two aneurysms of descending thoracic aorta. In an emergency operation, there was no abscess formation around the aneurysms. Aneurysms were excised en bloc without opening aneurysms followed by in situ Dacron tube graft replacement. The patient has been doing well without infection.     

Langerhans cell density in normal human oral mucosa and skin: relationship to age, smoking and alcohol consumption

Hyperthyroidism is a common endocrinologic disorder affecting many organ systems. Musculoskeletal and neurological involvement present themselves as fatigue, muscle weakness and paralysis. Electromyography (EMG) is essential for differential diagnosis of muscle weakness. Well defined neuropathy and myopathy have been described in these patients. In the present study 17 hyperthyroid patients were evaluated with electrophysiological tests in addition to physical and neurological examinations and biochemical laboratory studies. Needle EMG, motor and sensory conduction velocities, median and tibial somatosensory evoked potentials (SEP) were studied. For assessment of the activity of disease clinical status, neurological symptom and disability scores and serum T3, T4 and TSH levels were examined. Statistical analysis of neuroelectrophysiological findings of the patient and the control groups yielded meaningful difference in the needle EMG, sensory conduction velocity and evoked potential findings. Abnormalities were observed in 80% of the proximal muscles besides polyphasic potentials that were seen in 20% of the extensor digitorum brevis muscle. Median, ulnar and sural nerve sensory action potential amplitudes were found to be lower than that of the control group. Sural sensory nerve conduction velocity of patients was decreased in 35.5%, prolongation of median SEP latencies and increase in the amplitudes were not however statistically significant. Prolongation of Tibial SEP N1, P2 latencies were seen in 47%, amplitudes of N1 were increased in 88.2%, P2 in 58.8%, N2 in 47%. The thyroid clinical status score was correlated with Tibial SEPs amplitude. These findings suggest the presence of an initial axonal type of mild polyneuropathy. As a conclusion electrophysiological studies can be useful in the diagnosis of asymptomatic polyneuropathy in hyperthyroid patients.     

Gaze tutor: A gaze-reactive intelligent tutoring system

We developed an intelligent tutoring system (ITS) that aims to promote engagement and learning by dynamically detecting and responding to students' boredom and disengagement. The tutor uses a commercial eye tracker to monitor a student's gaze patterns and identify when the student is bored, disengaged, or is zoning out. The tutor then attempts to reengage the student with dialog moves that direct the student to reorient his or her attentional patterns towards the animated pedagogical agent embodying the tutor. We evaluated the efficacy of the gaze-reactive tutor in promoting learning, motivation, and engagement in a controlled experiment where 48 students were tutored on four biology topics with both gaze-reactive and non-gaze-reactive (control condition) versions of the tutor. The results indicated that: (a) gaze-sensitive dialogs were successful in dynamically reorienting students’ attentional patterns to the important areas of the interface, (b) gaze-reactivity was effective in promoting learning gains for questions that required deep reasoning, (c) gaze-reactivity had minimal impact on students’ state motivation and on self-reported engagement, and (d) individual differences in scholastic aptitude moderated the impact of gaze-reactivity on overall learning gains. We discuss the implications of our findings, limitations, future work, and consider the possibility of using gaze-reactive ITSs in classrooms.     

The interprocedural analysis and automatic parallelization of Scheme programs

Lisp and its descendants are among the most important and widely used of programming languages. At the same time, parallelism in the architecture of computer systems is becoming commonplace. There is a pressing need to extend the technology of automatic parallelization that has become available to Fortran programmers of parallel machines, to the realm of Lisp programs and symbolic computing. In this paper we present a comprehensive approach to the compilation of Scheme programs for shared-memory multiprocessors. Our strategy has two principal components:interprocedural analysis andprogram restructuring. We introduceprocedure strings andstack configurations as a framework in which to reason about interprocedural side-effects and object lifetimes, and develop a system of interprocedural analysis, using abstract interpretation, that is used in the dependence analysis and memory management of Scheme programs. We introduce the transformations ofexit-loop translation andrecursion splitting to treat the control structures of iteration and recursion that arise commonly in Scheme programs. We propose an alternative representation for s-expressions that facilitates the parallel creation and access of lists. We have implemented these ideas in a parallelizing Scheme compiler and run-time system, and we complement the theory of our work with snapshots of programs during the restructuring process, and some preliminary performance results of the execution of object codes produced by the compiler.This work was supported in part by the National Science Foundation under Grant No. NSF MIP-8410110, the U.S. Department of Energy under Grant No. DE-FG02-85ER25001, the Office of Naval Research under Grant No. ONR N00014-88-K-0686, the U.S. Air Force Office of Scientific Research under Grant No. AFOSR-F49620-86-C-0136, and by a donation from the IBM Corportation.