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Excessive expansion of adipose tissue in obesity typically leads to overflow and accumulation of lipids in other tissues, causing fatty liver disease and atherosclerosis. The intracellular protein, phosphoprotein enriched in astrocytes (PEA)-15 has been linked to metabolic disease but its role in lipid storage has not been examined. To delineate the role of PEA-15 in adipose tissue, we placed PEA-15-/- mice on a high fat diet. These mice developed increased body weight and greater white adipose tissue expansion compared to high fat diet-fed wild type mice. This was due to increased adipocyte cell size in PEA-15-/- mice consistent with greater lipid storage capacity. Surprisingly, PEA-15-/- mice exhibited improvements in whole body insulin sensitivity, lower hepatic weight and decreased serum triglycerides indicating a protective phenotype. To determine effects on atherosclerosis, PEA-15-/- mice were crossed with the ApoE-/- mice on a high fat diet. Strikingly, these mice were protected from atherosclerosis and had less hepatic lipid accumulation despite increased adiposity. Therefore, we reveal for the first time that PEA-15 plays a novel role in regulating the expansion of adipose tissue. Decreasing PEA-15 expression increases the sequestering of lipids in adipose tissue, protecting other tissues in obesity, thereby improving metabolic health.

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IR laser-induced gas-phase photolysis of Fe(CO)(5)-SiH(4) mixtures occurs as SiH(4)-photosensitized decomposition of Fe(CO)(5) is accelerated by products of this decomposition and it results in deposition of amorphous Si/Fe nanocomposite films. Analyses of the deposited and subsequently annealed solid films were made by FTIR, Raman and X-ray photoelectron spectroscopy, X-ray diffraction and electron microscopy. The deposited films are amorphous, contain crystalline nanostructures of iron silicide FeSi(2) and undergo atmospheric oxidation in topmost layers to iron oxide and hydrogenated silicon oxide. Upon annealing they develop nanocrystalline structures of ferrisilicate, Fe(1.6)SiO(4), carbon-encaged iron disilicide, FeSi(2), and very rare hexagonal (high-pressure) Fe surviving at ambient conditions. The mechanism of formation of these nanostructures is discussed in terms of gas-phase and solid-phase reactions.

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Degradation of 4,6-dimethyldibenzothiophene (DMDBT), persistent sulfur contaminant in fuel oils has been achieved in non-polar phase by laser-irradiating DMDBT alone and in the presence of hydrogen peroxide and molecular oxygen. The most efficient degradation in the presence of molecular oxygen is judged to be the first example of self-sensitized photo-oxygenation of thiophenes, in which DMDBT sequentially acts as 1O2 sensitizer and reactant.

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This randomised, double-blind, parallel-group, multicentre clinical trial evaluated the efficacy and safety of rupatadine, a new antihistamine with antiplatelet-activating factor (PAF) activity, and cetirizine in the treatment of patients with seasonal allergic rhinitis (SAR). A total 249 patients were randomised to receive rupatadine 10 mg once daily (127 patients) or cetirizine 10 mg (122 patients) for two weeks. The main efficacy variable was the mean total daily symptom score (mTDSS) and was based on the daily subjective assessment of the severity of each rhinitis symptom--nasal (runny nose, sneezing, nasal itching and nasal obstruction) and non-nasal (conjunctival itching, tearing, and pharyngeal itching)--recorded by patients in their diaries. The mTDSS was 0.7 for both treatment groups (intention to treat analysis). In the investigator's global evaluation of efficacy at the seventh day, 93.3% and 83.7% patients in the rupatadine and cetirizine groups, respectively, showed some or great improvement (p = 0.022). In the per protocol analysis (n = 181), runny nose at the seventh day of treatment was absent or mild in 81.1% of patients in the rupatadine group and in 68.6% of patients in the cetirizine group (p = 0.029). In any case statistical significance was not maintained at the second week. Overall, all treatments were well tolerated. Adverse events (AEs) were similar in both treatment groups, i.e. headache, somnolence and fatigue/asthenia as the most often reported. Somnolence was reported in 9.6% and 8.5% of patients treated with rupatadine or cetirizine, respectively. The most reported AEs (67%) were mild in intensity. Our results suggest that rupatadine 10 mg may be a valuable and safe alternative for the symptomatic treatment of SAR.

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The identification of trimethylsiloxy-1,2-dioxetane and 2-trimethylsilyloperoxyacetaldehyde and assignment of trimethylsiloxymethyl formate as products of the low-temperature ozonolysis of trimethylsilylethene demonstrate feasibility of migrations of trimethylsilyl group in a dioxygen-centered (oxyperoxy) diradical produced via a homolytic cleavage of each of both O-O bonds in the primary ozonide. The results provide the first experimental evidence on the nonconcerted decomposition of the primary ozonide.

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Subjects smoothly pursued a target moving horizontally at 15 deg/s. After pursuit for 1 s, the target jumped 3 deg ahead of the fovea. At the moment of the jump, target velocity became 0 and 'effective visual feedback' assumed a value of either 0 (target retinally stabilized), -0.2, -0.4, or -1.0 (target fixed in space). With 0 visual feedback the eye continued to move smoothly at a moderate velocity, an apparent response to target position relative to the fovea. When negative visual feedback was present eye velocity decreased. With -0.2 and -0.4 feedback, this decrease was not a simple exponential, but often consisted of an initial fast decrease followed by slower decrease. With -1.0 feedback, eye velocity quickly decreased in an approximately exponential manner, and stopped. We were able to simulate these pursuit responses using a simple model of the pursuit system. Key features of the model are: (a) a target-velocity channel whose output decreases with target offset from the fovea, and whose gain switches from high to low as pursuit velocity approaches zero; (b) a target-position channel with a saturation non-linearity at 1-3 deg; and (c) a positive feedback loop with gain of less than 1.0. All of these features are essential to simulate the pursuit responses, especially with visual feedback values of -0.2 and -0.4. Our results and model suggest that target position serves as an important stimulus in guiding smooth pursuit as pursuit velocity decreases, and especially during pursuit termination.

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The perceived size of 'P' and 'p' is influenced by their vertical position relative to nearby letters. In the experiments reported here, we show that uppercase 'P' appears smallest when it is displaced downward toward the letter's lowercase position, whereas lowercase 'p' appears largest when it is near the uppercase position. Our results show that this P-illusion not only occurs in the presence of nearby letters, but is also found when 'P' is displaced relative to a nearby horizontal line. This type of size illusion seems to clearly occur only with 'P' and 'p', and we suggest that it is a result of learning to read and recognize letters in the English alphabet.

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ArF (193 nm) and KrF (248 nm) laser-induced photolysis of gaseous selenophene and tellurophene (C4H4M, M=Se and Te) has been examined. It is shown that, unlike thiophene and furan, selenophene and tellurophene cleave both M-C bonds and yield the elemental heteroatom (Se, Te), 1-buten-3-yne, and ethyne. The proposed mechanism involves an intermediate .HC=CH-CH=CH. diradical that decomposes via two competitive pathways, namely, 1,3-H shift to 1-buten-3-yne and beta-cleavage to two molecules of ethyne. It is shown that the relative importance of the channels depends both on the energy of the photon and on the heteroatom. Specifically, the 1,3-H shift/beta-cleavage ratios are 2.3 (193 nm, M=Se), 3.6 (248 nm, M=Se), 1.4 (193 nm, M=Te), and 10.5 (248 nm, M=Te). The inertness of the Te residuum and the high preference for the 1,3-H shift in KrF laser photolysis of tellurophene suggest that this photolysis can serve as a source of the C4H4 diradical for mechanistic studies.

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This study describes the discovery and diagnosis of malignant tumors from a primary care perspective in a Swedish county. Between 1984 and 1995, 68 children between the ages 0-16 years were diagnosed with a malignant tumor giving an incidence of 14/100,000. Patient records from both primary care and hospital were analyzed for 64 children. Leukemia was diagnosed in 25 children, and brain tumors in 22 children. In 68% of the children the diagnostic process was initiated in primary care, and in 32% in specialist care. Median parent's delay (time from first symptoms to first consultation), and median doctor's delay (time from first consultation to diagnosis) were 5 and 3 weeks for children with brain tumors, and 1 and 0 weeks for children with leukemia. Median lag time (parent's + doctor's delay) was 9 weeks for patients with brain tumors and 3 weeks for children with leukemia.

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Subjects made smooth pursuit eye movements with a target moving horizontally at 15 deg/sec. At a specified location the target either: (1) suddenly vanished; or (2) jumped to the fovea with target retinal velocity and feedback becoming 0 (target stabilized at the fovea). In each type of trial, the subjects either: "looked" at the target, "pushed" the target, or "passively" gazed. When the target vanished, eye velocity decreased exponentially with a short time-constant (tau approximately 0.10 sec), regardless of whether the subjects were "looking," "pushing" or "passively" gazing. However, some subjects while "pushing" (using an imaginary target) did generate low velocity smooth movement (1-2.5 deg/sec) late in the offset. When the target was stabilized at the fovea, eye velocity also decreased, but with a relatively long time-constant (tau = 0.4-0.8 sec). The time-constant was the same with both "looking," and "pushing", but was shorter for some subjects with "passive" gazing (tau = 0.1-0.5 sec). These findings show that smooth pursuit offset is influenced by the presence of a target, but is relatively independent of attentional mode. All of the pursuit offset responses can be simulated using a model of the pursuit system with target velocity and position inputs, and an internal positive feedback loop enabled by target presence.

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In previous work, subjects looked at a target stabilized at the fovea, superimposed on a sinusiodally moving OKN stimulus. The stabilized target (no retinal-slip) suppressed OKN leaving residual eye movements that were often in counterphase with the OKN stimulus motion. In the present study we explored how this type of suppression of OKN is influenced by OKN stimulus predictability: OKN stimulus motion was either sinusoidal or a random walk of half-sinusoids. During fixation of a stabilized target with sinusoidal stimulus motion, OKN was suppressed leaving residual eye movement whose amplitude was typically less than OKN and with a phase lag of about 180 deg (roughly in counterphase with stimulus motion). With random-walk stimulus motion, the residual movement amplitude was even smaller, and at higher frequencies the phase lag decreased to become the same as for OKN. For both stimulus motions, OKN was suppressed when the target was present, but counterphase residual movements appear to depend on stimulus predictability.

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The ability to maintain foveal fixation of a target with either a stationary or moving background is often assumed to depend primarily on a difference (in velocity and/or position) between fovea and target. However, when subjects look at a target stabilized at the fovea presented against sinusoidal motion of an optokinetic stimulus field, optokinetic nystagmus (OKN) is suppressed. This suppression is not simply the absence of movement but instead most subjects show some amount of residual slow eye movements roughly counterphase to the field motion. We have varied the visual feedback of the target from 0 (stabilized) to -1 (stationary in space); as feedback increased, amplitude and phase lag of residual eye movements decreased systematically. The mechanism responsible for residual movements appears to operate for all feedback values (including the "real world" value of -1), which suggests a new view of the role played by retinal slip during fixation of a target and suppression of OKN.

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Initiation of smooth pursuit eye movements was studied using imaginary targets defined by pairs of small spots ("cues") moving together in step-ramp motion. The arrangement of cues and imaginary target were either "two-sided"--cues far apart and imaginary target midway between, or "one-sided"--cues 4 deg apart and imaginary target to one side of the cue pair. (1) Pursuit of two-sided stimuli was much better than pursuit of one-sided stimuli and was often as good as pursuit of a real foveal target. (2) Experiments with various cue configurations suggest an attribute required for vigorous pursuit: "foveal enclosure". Configuration information is available to the pursuit system immediately after the onset of motion. (3) Pursuit of imaginary targets is markedly degraded by a background; the effect is strongest for a background at the fovea and weaker for an eccentric background, including one at the cue location.

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Subjects viewed a foveally stabilized target presented against a background field of dots moving sinusoidally. Several different modes of viewing the target were used (subjects were instructed to gaze, look, or hold), and the frequency of sinusoidal field motion was varied from 1/32 to 2 Hz. In line with previous findings, the presence of a stabilized target resulted in substantial suppression of optokinesis. The characteristics of this suppression (gain and phase of slow residual eye movements) were dependent on both the mode of viewing the target and the frequency of field motion. When subjects used an imaginary target, little suppression occurred. These findings provide an overall profile of dynamic characteristics of mechanisms involved in the suppression of optokinesis. They support the view that this suppression is significantly determined by the presence of a target against a moving background (even without retinal slip), and by the mode of attending to the target.

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Macrolides, which are widely prescribed and seldom produce hypersensitivity reactions, are considered to be safe drugs. We present five patients with generalized skin reactions due to erythromycin and/or spiramycin, proved by oral challenge tests. One patient showed reactions to both erythromycin and spiramycin. All skin prick and patch tests and histamine release tests with both macrolides were negative.

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We explored the influence of changing size and blur on accommodation by presenting the two stimuli sinusoidally in counterphase. The frequency response of the accommodative system (0.05 to 1 Hz) was determined using a high-speed infrared optometer while the subject viewed the target in a Badal optometer. Blur was provided by moving the target dioptrically toward and away from the subject, and size of the target was altered by a variable aperture. Both stimuli were varied sinusoidally at the same frequency, but in counterphase. We find that both size and blur can have an influence on accommodation: blur is particularly powerful at low temporal frequencies, whereas size becomes effective at moderate and high temporal frequencies.

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During smooth pursuit eye movement, the perception of target motion appears to come from retinal and extraretinal influences. To explore this, two open-loop conditions (experimental stimuli stabilized at the retina) were used: one to look at the combined effect of retinal and extraretinal signals on perception (using sinusoidal target motion); and the other to look at the characteristics of an extraretinal signal alone (using a complex target and square-wave motion). In both conditions subjects tracked target motion in the dark, and subsequently compared it to motion of a similar target in the light. The main findings of the study are that the magnitude of the extraretinal signal decreases with frequency, and that the retinal and extraretinal signals combine additively. This system appears to involve a transport-time, which could be in the form of a time advance. These features of perception have a variety of implications for motor control.

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