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In a recent publication, Boutin et al. (1979) have presented some circuits ideas on a broadband square-wave frequency multiplier. These circuits need a comparator type A/D converter which is both rare and expensive. In the present paper, some new circuits are presented in which the A/D converters have been replaced by D/A converters which are cheaper and more accessible. [ABSTRACT FROM AUTHOR]

A simple circuit is proposed to simultaneously multiply by factors 2[sub i-1] (l ≤i≤N) the frequency of an incoming square wave. Each output square wave of 50% duty cycle is synchronized with the input signal whose frequency can be varied over many decades. [ABSTRACT FROM AUTHOR]

Background and Aims: To describe the change in glucose and the resulting postprandial hyperglycemia (PPH) that occurs after dietary protein intake (PI) in children with type 1 diabetes (T1D)., Methods: We conducted a self-controlled, non-randomized, prospective pilot study in children with T1D who were given whey protein isolate drinks (carbohydrate-free, fat-free) of increasing protein amounts (0, 12.5, 25, 37.5, 50, and 62.5 gm) on 6 sequential nights. The glucose levels were monitored with continuous glucose monitors (CGM) and glucometers for 5 h after PI. PPH was defined as glucose elevations over baseline of ≥50 mg/dL., Results: Thirty-eight subjects were recruited, and eleven subjects (6 females, 5 males) completed the intervention. Subjects had a mean (range) age of 11.6 (6-16) years, diabetes duration of 6.1 (1.4-15.5) years, HbA1c of 7.2 (5.2-8.6) % and weight of 44.5 (24.3-63.2) kg. PPH was detected in 1/11, 5/11, 6/10, 6/9, 5/9, and 8/9 subjects after receiving 0, 12.5, 25, 37.5, 50, and 62.5 gm of protein, respectively., Conclusions: In children with T1D, the association between PPH and PI was observed at smaller protein amounts compared to studies done in adults., Competing Interests: Declaration of competing interest The authors have no financial relationships relevant to this article to disclose., (Copyright © 2023 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Insulin resistance is frequently present in patients with glucocorticoid (GC) excess (Cushing's syndrome) or treated with high doses of GCs. Furthermore, others similarities between metabolic syndrome (visceral obesity, elevated blood glucose levels, dyslipidemia) and Cushing's syndrome suggest that GCs could play a role in obesity-linked complications. Here we reported that long-term corticosterone (CORT) exposure in mice induced weight gain, dyslipidemia as well as hyperglycaemia and systemic insulin resistance. CORT-treated mice exhibited an increased 11β-Hsd1 expression and corticosterone levels in fat depots but a specific upregulation of glucocorticoid receptor (Gr) and hexose-6-phosphate dehydrogenase only in gonadal adipose tissue, suggesting that GC could act differentially on various fat depots. Despite fat accumulation in all depots, an increased expression of adipogenic (Pparγ, C/ebpα) and lipogenic (Acc, Fas) key genes was restricted to gonadal adipose tissue. Hypertrophied adipocytes observed in both visceral and subcutaneous depots also resulted from reduced lipolytic activity due to CORT treatment. Surprisingly, GC treatment promoted macrophage infiltration (F4/80, Cd68) within all adipose tissues along with predominant M2-like macrophage phenotype, and can directly act on macrophages to induce this phenotype. Moreover, macrophage infiltration preceded mass gain and adipocyte hypertrophy. Of note, specific macrophage depletion in gonadal fat preferentially reduced the M2-like macrophage content, and partially restored insulin sensitivity in mice with GC-induced obesity and insulin resistance. These data provide evidence that GCs act on adipose tissue in a depot-dependent manner and that gonadal adipose macrophages are key effectors of GC-associated insulin resistance., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The HERMES beamline (High Efficiency and Resolution beamline dedicated to X-ray Microscopy and Electron Spectroscopy), built at Synchrotron SOLEIL (Saint-Auban, France), is dedicated to soft X-ray microscopy. The beamline combines two complementary microscopy methods: XPEEM (X-ray Photo Emitted Electron Microscopy) and STXM (Scanning Transmission X-ray Microscopy) with an aim to reach spatial resolution below 20 nm and to fully exploit the local spectroscopic capabilities of the two microscopes. The availability of the two methods within the same beamline enables the users to select the appropriate approach to study their specific case in terms of sample environment, spectroscopy methods, probing depth etc. In this paper a general description of the beamline and its design are presented. The performance and specifications of the beamline will be reviewed in detail. Moreover, the article is aiming to demonstrate how the beamline performances have been specifically optimized to fulfill the specific requirements of a soft X-ray microscopy beamline in terms of flux, resolution, beam size etc. Special attention has been dedicated to overcome some limiting and hindering problems that are usually encountered on soft X-ray beamlines such as carbon contamination, thermal stability and spectral purity.

Vancomycin-resistant enterococci (VRE) are a growing health problem, and uncertainties exist regarding the optimal therapy for bloodstream infection due to VRE. We conducted systematic comparative evaluations of the impact of different antimicrobial therapies on the outcomes of patients with bloodstream infections due to VRE. A retrospective study from January 2008 to October 2010 was conducted at Detroit Medical Center. Unique patients with blood cultures due to VRE were included and reviewed. Three major therapeutic classes were analyzed: daptomycin, linezolid, and β-lactams. Three multivariate models were conducted for each outcome, matching for a propensity score predicting the likelihood of receipt of one of the therapeutic classes. A total of 225 cases of bacteremia due to VRE were included, including 86 (38.2%) cases of VR Enterococcus faecalis and 139 (61.8%) of VR Enterococcus faecium. Bacteremia due to VR E. faecalis was more frequent among subjects treated with β-lactams than among those treated with daptomycin or linezolid. The median dose of daptomycin was 6 mg/kg of body weight (range, 6 to 12 mg/kg). After controlling for propensity score and bacteremia due to VR E. faecalis, differences in mortality were nonsignificant among the treatment groups. Therapy with daptomycin was associated with higher median variable direct cost per day than that for linezolid. This large study revealed the three therapeutic classes (daptomycin, linezolid, and β-lactams) are similarly efficacious in the treatment of bacteremia due to susceptible strains of VRE., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

X-ray diffraction is an extremely important tool for structure determination of biological macromolecules, to the extent that currently around 85% of Protein Data Bank entries result from X-ray measurements. Many of these structure determinations use synchrotron radiation for data collection. This article aims to give synchrotron users an overview of the functioning of a synchrotron beamline and how the performance of various instruments combines to allow the collection of diffraction data.

We recently showed that hypoxia does not induce active expiratory glottic adduction in awake lambs more than 10 d old. To reconcile our results with previous data from other researchers, we hypothesized that an active expiratory glottic closure might still be part of the response to hypoxia in the very first postnatal days. The present study was undertaken to test this hypothesis. We studied 22 awake, nonsedated lambs during hypocapnic hypoxia (fraction of inspired O2 = 0.08 during 15 min) induced during the first 72 h of postnatal life. We recorded airflow via a facial mask and pneumotachograph, along with the electromyographic activity (EMG) of the thyroarytenoid muscle (a glottic adductor) in 10 lambs. We also recorded the EMG of both the posterior cricoarytenoid (n = 4) and cricothyroid (n = 5) muscles (glottic abductors), as well as the abdominal muscles (n = 4). We identified typical expiratory airflow braking on the breath-by-breath computed flow-volume loop and thyroarytenoid muscle expiratory EMG as evidence of active expiratory glottic adduction. We found that hypoxia induced a biphasic ventilatory response, with an early peak and a subsequent decrease, and that active expiratory glottic adduction was absent during baseline room-air breathing and hypoxia. We also found that the glottic abductor phasic inspiratory and tonic expiratory EMG as well as the abdominal muscle phasic expiratory EMG, all of which were present during baseline recording, increased during hypoxia. We conclude that hypoxia does not induce expiratory glottic closure in the very first days of life in awake lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the relationships of asbestos exposure, retention, airway response, and the asbestos alveolitis, we exposed 2 groups of sheep every 2 wk for 3 yr to either 100 ml phosphate-buffered saline (PBS) or 100 mg UICC chrysotile fibers in 100 ml PBS. The sheep were evaluated periodically by pulmonary function tests (PFT), chest radiograph (CR), bronchoalveolar lavage (BAL), and transbronchial lung biopsy (TLB). At Month 24 of the study, all asbestos-exposed sheep had significant increases in lung resistance and upstream resistance. However, only 9 of the 16 asbestos-exposed sheep had significant changes in TLB, CR, Cst, and VC, which clearly separated them from the other 6 sheep in these parameters. The 2 groups, however, had similar air-flow limitation. At lung biopsy, all asbestos-exposed sheep had significant peribronchiolar fibrosis, with significant alveolitis only in the group of 9 sheep with radiographic and functional changes of early asbestosis. The 9 sheep also had significant changes in BAL cellularity and biochemical profile, which differentiated them from the other 6 asbestos-exposed sheep. Analysis of BAL fiber content at that point revealed that despite identical exposure, the group with interstitial lung disease had significantly more fiber retention (p less than 0.01). The data demonstrate that whereas asbestos airway disease appears to be primarily an exposure-dose-related response, the lung response appears to be more closely related to alveolar retention of the dust.

Neonates of various species including lambs respond to hypoxia by a transient hyperventilation followed by a VE depression (diphasic response). To better delineate the role of the carotid chemoreceptors and that of the central depressive/inhibitive effect of hypoxia on minute ventilation, we have studied the VE response of 4-day-old carotid body-deprived lambs (CBD) during successive exposure to moderate and severe (0.12 and 0.07 FIO2) hypoxia. The carotid body denervation was done to abolish most of the chemoreceptor stimulating effect on VE during hypoxia and to allow for central depression/inhibition of VE during hypoxia. In the CBD lambs, baseline VE was 461 +/- 81 (SE) ml X (kg X min)-1. It increased to 532 +/- 79 ml X (kg X min)-1 and to 541 +/- 75 ml X (kg X min)-1, to 0.12 FIO2 and 0.07 FIO2. These VE increases did not reach level of significance (P greater than 0.05). After 2-5 min of both levels of hypoxia VE dropped respectively to 460 +/- 60 ml X (kg X min)-1 and to 459 +/- 38 ml X (kg X min)-1. No marked ventilatory depressions were noted but VE had only returned to baseline. It is concluded that, in the denervated newborn lamb, the centrally mediated depressive effect of hypoxia is small and not sufficient to explain the diphasic VE response of the intact lamb to steady state hypoxia. Analysis of the magnitude of the hyperventilation and the VE damping pre-hypoxic levels occurring with sustained hypoxia in newborns of various species suggests that the immaturity of the O2-sensitive chemoreceptor rather than the central effect of hypoxia is the determinant factor of the diphasic response of newborn mammals to hypoxic hypoxia.

To evaluate the time course and mechanisms of enhanced 67Ga lung uptake in asbestosis, we exposed two groups of sheep every 2 wk to either 100 ml saline (controls) or 100 mg UICC chrysotile fibers in 100 ml saline. The sheep were evaluated periodically by pulmonary function tests (PFT), thoracic radiograph (TR), 67Ga lung scan bronchoalveolar lavage (BAL), and transbronchial lung biopsy (TLB). By month 24 of the study, 9/15 exposed sheep had developed the initial alveolitis and had significant changes in PFT, TR, and TLB. The other six exposed sheep differed from controls only by a 75% increase in BAL fibronectin until month 30, where significant changes in albumin occurred and 67Ga scan score increased. The nine sheep with alveolitis had significant sustained increases in 67Ga scan and BAL levels from month 6, associated with a 150% increase in BAL fibronectin and other parameters of disease activity changed from month 18 to 30. We concluded that in the sheep model of asbestosis, significant changes in 67Ga scan, 67Ga BAL counts, and excessive elevation of BAL fibronectin preceded other parameters of disease activity. The data suggest that excessively activated macrophages are primarily responsible for the early 67Ga lung uptake.