Low-Frequency Spectral Turn-Overs in Millisecond Pulsars Studied from Imaging Observations

Measurements of pulsar flux densities are of great importance for understanding the pulsar emission mechanism and for predictions of pulsar survey yields and the pulsar population at large. Typically these flux densities are determined from phase-averaged "pulse profiles", but this method has limited applicability at low frequencies because the observed pulses can easily be spread out by interstellar effects like scattering or dispersion, leading to a non-pulsed continuum component that is necessarily ignored in this type of analysis. In particular for the class of the millisecond pulsars (MSPs) at frequencies below 200MHz, such interstellar effects can seriously compromise de- tectability and measured flux densities. In this paper we investigate MSP spectra based on a complementary approach, namely through investigation of archival con- tinuum imaging data. Even though these images lose sensitivity to pulsars since the on-pulse emission is averaged with off-pulse noise, they are insensitive to effects from scattering and provide a reliable way to determine the flux density and spectral indices of MSPs based on both pulsed and unpulsed components. Using the 74MHz VLSSr as well as the 325MHz WENSS and 1.4GHz NVSS catalogues, we investigate the imaging flux densities of MSPs and evaluate the likelihood of spectral turn-overs in this population. We determine three new MSP spectral indices and identify six new MSPs with likely spectral turn-overs.Comment: 10 pages, 4 figures, 3 tables, accepted for publication in MNRA

The nature of the low-frequency emission of M51: First observations of a nearby galaxy with LOFAR

The grand-design spiral galaxy M51 was observed with the LOFAR High Frequency Antennas (HBA) and imaged in total intensity and polarisation. This observation covered the frequencies between 115 MHz and 175 MHz. We produced an image of total emission of M51 at the mean frequency of 151 MHz with 20 arcsec resolution and 0.3 mJy rms noise, which is the most sensitive image of a galaxy at frequencies below 300 MHz so far. The integrated spectrum of total radio emission is described well by a power law, while flat spectral indices in the central region indicate thermal absorption. We observe that the disk extends out to 16 kpc and see a break in the radial profile near the optical radius of the disk. Our main results, the scale lengths of the inner and outer disks at 151 MHz and 1.4 GHz, arm--interarm contrast, and the break scales of the radio--far-infrared correlations, can be explained consistently by CRE diffusion, leading to a longer propagation length of CRE of lower energy. The distribution of CRE sources drops sharply at about 10 kpc radius, where the star formation rate also decreases sharply. We find evidence that thermal absorption is primarily caused by HII regions. The non-detection of polarisation from M51 at 151 MHz is consistent with the estimates of Faraday depolarisation. Future searches for polarised emission in this frequency range should concentrate on regions with low star formation rates.Comment: 20 pages, 18 figures, accepted for publication in A&

Clinical and Genetic Characteristics of 18 Patients from 13 Japanese Families with CRX-associated retinal disorder: Identification of Genotype-phenotype Association

Inherited retinal disorder (IRD) is a leading cause of blindness, and CRX is one of a number of genes reported to harbour autosomal dominant (AD) and recessive (AR) causative variants. Eighteen patients from 13 families with CRX-associated retinal disorder (CRX-RD) were identified from 730 Japanese families with IRD. Ophthalmological examinations and phenotype subgroup classification were performed. The median age of onset/latest examination was 45.0/62.5 years (range, 15–77/25–94). The median visual acuity in the right/left eye was 0.52/0.40 (range, −0.08–2.00/−0.18–1.70) logarithm of the minimum angle of resolution (LogMAR) units. There was one family with macular dystrophy, nine with cone-rod dystrophy (CORD), and three with retinitis pigmentosa. In silico analysis of CRX variants was conducted for genotype subgroup classification based on inheritance and the presence of truncating variants. Eight pathogenic CRX variants were identified, including three novel heterozygous variants (p.R43H, p.P145Lfs*42, and p.P197Afs*22). A trend of a genotype-phenotype association was revealed between the phenotype and genotype subgroups. A considerably high proportion of CRX-RD in ADCORD was determined in the Japanese cohort (39.1%), often showing the mild phenotype (CORD) with late-onset disease (sixth decade). Frequently found heterozygous missense variants located within the homeodomain underlie this mild phenotype. This large cohort study delineates the disease spectrum of CRX-RD in the Japanese population

Genetic Spectrum of EYS-associated Retinal Disease in a Large Japanese Cohort: Identification of Disease-associated Variants with Relatively High Allele Frequency

Biallelic variants in the EYS gene are a major cause of autosomal recessive inherited retinal disease (IRD), with a high prevalence in the Asian population. The purpose of this study was to identify pathogenic EYS variants, to determine the clinical/genetic spectrum of EYS-associated retinal disease (EYS-RD), and to discover disease-associated variants with relatively high allele frequency (1%-10%) in a nationwide Japanese cohort. Sixty-six affected subjects from 61 families with biallelic or multiple pathogenic/disease-associated EYS variants were ascertained by whole-exome sequencing. Three phenotype groups were identified in EYS-RD: retinitis pigmentosa (RP; 85.94%), cone-rod dystrophy (CORD; 10.94%), and Leber congenital amaurosis (LCA; 3.12%). Twenty-six pathogenic/disease-associated EYS variants were identified, including seven novel variants. The two most prevalent variants, p.(Gly843Glu) and p.(Thr2465Ser) were found in 26 and twelve families (42.6%, 19.7%), respectively, for which the allele frequency (AF) in the Japanese population was 2.2% and 3.0%, respectively. These results expand the phenotypic and genotypic spectrum of EYS-RD, accounting for a high proportion of EYS-RD both in autosomal recessive RP (23.4%) and autosomal recessive CORD (9.9%) in the Japanese population. The presence of EYS variants with relatively high AF highlights the importance of considering the pathogenicity of non-rare variants in relatively prevalent Mendelian disorders

Day-night variation of acute myocardial infarction in obstructive sleep apnea.

OBJECTIVES: This study sought to evaluate the day-night variation of acute myocardial infarction (MI) in patients with obstructive sleep apnea (OSA). BACKGROUND: Obstructive sleep apnea has a high prevalence and is characterized by acute nocturnal hemodynamic and neurohormonal abnormalities that may increase the risk of MI during the night. METHODS: We prospectively studied 92 patients with MI for which the time of onset of chest pain was clearly identified. The presence of OSA was determined by overnight polysomnography. RESULTS: For patients with and without OSA, we compared the frequency of MI during different intervals of the day based on the onset time of chest pain. The groups had similar prevalence of comorbidities. Myocardial infarction occurred between 12 am and 6 am in 32% of OSA patients and 7% of non-OSA patients (p = 0.01). The odds of having OSA in those patients whose MI occurred between 12 am and 6 am was 6-fold higher than in the remaining 18 h of the day (95% confidence interval: 1.3 to 27.3, p = 0.01). Of all patients having an MI between 12 am and 6 am, 91% had OSA. CONCLUSIONS: The diurnal variation in the onset of MI in OSA patients is strikingly different from the diurnal variation in non-OSA patients. Patients with nocturnal onset of MI have a high likelihood of having OSA. These findings suggest that OSA may be a trigger for MI. Patients having nocturnal onset of MI should be evaluated for OSA, and future research should address the effects of OSA therapy for prevention of nocturnal cardiac events

The LOFAR long baseline snapshot calibrator survey

Aims. An efficient means of locating calibrator sources for international LOw Frequency ARray (LOFAR) is developed and used to determine the average density of usable calibrator sources on the sky for subarcsecond observations at 140 MHz. Methods. We used the multi-beaming capability of LOFAR to conduct a fast and computationally inexpensive survey with the full international LOFAR array. Sources were preselected on the basis of 325 MHz arcminute-scale flux density using existing catalogues. By observing 30 different sources in each of the 12 sets of pointings per hour, we were able to inspect 630 sources in two hours to determine if they possess a sufficiently bright compact component to be usable as LOFAR delay calibrators. Results. More than 40% of the observed sources are detected on multiple baselines between international stations and 86 are classified as satisfactory calibrators. We show that a flat low-frequency spectrum (from 74 to 325 MHz) is the best predictor of compactness at 140 MHz. We extrapolate from our sample to show that the sky density of calibrators that are sufficiently bright to calibrate dispersive and non-dispersive delays for the international LOFAR using existing methods is 1.0 per square degree. Conclusions. The observed density of satisfactory delay calibrator sources means that observations with international LOFAR should be possible at virtually any point in the sky provided that a fast and efficient search, using the methodology described here, is conducted prior to the observation to identify the best calibrator

The Anti-Inflammatory and Antibacterial Basis of Human Omental Defense: Selective Expression of Cytokines and Antimicrobial Peptides

BACKGROUND: The wound healing properties of the human omentum are well known and have extensively been exploited clinically. However, the underlying mechanisms of these effects are not well understood. We hypothesize that the omentum tissue promotes wound healing via modulation of anti-inflammatory pathways, and because the omentum is rich in adipocytes, the adipocytes may modulate the anti-inflammatory response. Factors released by human omentum may affect healing, inflammation and immune defense. METHODOLOGY: Six human omentum tissues (non obese, free from malignancy, and any other systemic disorder) were obtained during diagnostic laparoscopies having a negative outcome. Healthy oral mucosa (obtained from routine oral biopsies) was used as control. Cultured adipocytes derived from human omentum were exposed to lipopolysaccharide (LPS) (1-50 ng/mL) for 12-72 hours to identify the non-cytotoxic doses. Levels of expression (mRNA and protein) were carried out for genes associated with pro- and anti-inflammatory cytokine responses and antibacterial/antimicrobial activity using qRT-PCR, western blotting, and cell-based ELISA assays. RESULTS: The study shows significant higher levels of expression (mRNA and protein) of several specific cytokines, and antibacterial peptides in the omentum tissues when compared to oral sub-mucosal tissues. In the validation studies, primary cultures of adipocytes, derived from human omentum were exposed to LPS (5 and 10 ng/mL) for 24 and 48 h. The altered expressions were more pronounced in cultured adipocytes cells when exposed to LPS as compared to the omentum tissue. CONCLUSIONS/SIGNIFICANCE: Perhaps, this is the first report that provides evidence of expressional changes in pro- and anti-inflammatory cytokines and antibacterial peptides in the normal human omentum tissue as well as adipocytes cultured from this tissue. The study provides new insights on the molecular and cellular mechanisms of healing and defense by the omentum, and suggests the potential applicability of cultured adipocytes derived from the omentum for future therapeutic applications