Erratum:

This corrects the article DOI: 10.1103/PhysRevLett.123.033201.

Systematic uncertainty due to background-gas collisions in trapped-ion optical clocks.

We describe a framework for calculating the frequency shift and uncertainty of trapped-ion optical atomic clocks caused by background-gas collisions, and apply this framework to an 27Al+ clock to enable a total fractional systematic uncertainty below 10-18. For this clock, with 38(19) nPa of room-temperature H2 background gas, we find that collisional heating generates a non-thermal distribution of motional states with a mean time-dilation shift of order 10-16 at the end of a 150 ms probe, which is not detected by sideband thermometry energy measurements. However, the contribution of collisional heating to the spectroscopy signal is highly suppressed and we calculate the BGC shift to be -0.6(2.4) × 10-19, where the shift is due to collisional heating time dilation and the uncertainty is dominated by the worst case ±π/2 bound used for collisional phase shift of the 27Al+ superposition state. We experimentally validate the framework and determine the background-gas pressure in situ using measurements of the rate of collisions that cause reordering of mixed-species ion pairs.

Note: Design and implementation of a home-built imaging system with low jitter for cold atom experiments.

A novel home-built system for imaging cold atom samples is presented using a readily available astronomy camera which has the requisite sensitivity but no timing-control. We integrate the camera with LabVIEW achieving fast, low-jitter imaging with a convenient user-defined interface. We show that our system takes precisely timed millisecond exposures and offers significant improvements in terms of system jitter and readout time over previously reported home-built systems. Our system rivals current commercial "black box" systems in performance and user-friendliness.

The effect of body position on developing ultrasound criteria for the assessment of the internal jugular vein.

Recent studies investigating chronic cerebrospinal venous insufficiency highlighted that intracranial venous return has not yet been routinely investigated by ultrasound in the normal population. This creates an absence of a reference standard and raises concerns that the approach introduces variations into the results. The primary objective of this study was to develop reference standards for the assessment of the internal jugular vein in a normal population. A prospective small-scale study was conducted. Internal jugular veins of 31 normal candidates were examined using B-Mode and PW Doppler. Measurements at proximal and mid-point internal jugular vein were taken in sitting (90°) and supine (0°) positions. Area measurements were taken during passive respiration in cm(2). Time average velocity measurements were taken during passive respiration over a 3-second period. Reflux measurements were taken after apnoea and reflux was recorded from any reversed flow. Measurements were taken three times; an average was calculated and statically analysed. Of the 31 participants, one was excluded from the study and 30 were suitable. The Mann-Whitney U test was used to analyse the results; all results (area, time average velocity and reflux) showed that there was a significant difference between the two positions with p < 0.05 (two-tailed). This pilot study does suggest that there is a significant difference in area, time average velocity and reflux measurements of the internal jugular vein when taken in the sitting and supine position, which could affect the outcome of chronic cerebrospinal venous insufficiency. A further large-scale study is required to validate and standardise the assessment of the internal jugular vein.

Erythropoietin and erythropoietin receptor expression in human cancer.

Erythropoietin (EPO) stimulates the growth of erythroblasts in the bone marrow (C. Lacombe and P. Mayeux, NEPHROL: DIAL: TRANSPLANT:, 14 (SUPPL: 2): 22-28, 1999). We report basal and hypoxia-stimulated expression of EPO and its receptor, EPOR, in human breast cancer cells, and we demonstrate EPO-stimulated tyrosine phosphorylation and the proliferation of these cells in vitro. In 50 clinical specimens of breast carcinoma, we report high levels of EPO and EPOR associated with malignant cells and tumor vasculature but not with normal breast, benign papilloma, or fibrocystic tissue. Hypoxic tumor regions display the highest levels of EPO and EPOR expression. Enhanced EPO signaling may contribute to the promotion of human cancer by tissue hypoxia.

Characterization of hereditary nonpolyposis colorectal cancer families from a population-based series of cases.

BACKGROUND: The incidence of hereditary nonpolyposis colon cancer (HNPCC) in the general population is not well defined because of the lack of large population-based studies. We characterized the incidence of HNPCC in a large, population-based cohort of colorectal cancer probands and analyzed the location of colorectal tumors. METHODS: Of the participating 1134 probands from three counties in Southern California, 907 had a negative family history of colorectal cancer and 227 had a positive family history of colorectal cancer. In addition, 11 referral case subjects with HNPCC were used to study mutation frequencies in two mismatch repair genes (MSH2 and MLH1) and microsatellite instability. All statistical tests were two-sided. RESULTS: Among the probands diagnosed in Orange County during 1994 (population-based sample, all ages), five were consistent with the Amsterdam criteria for HNPCC (0.9%; 95% confidence interval [CI] = 0. 3%-2.1%). Among probands diagnosed at less than 65 years of age-from the wider three-county area and a longer time span-16 (2.1%; 95% CI = 1.2%-3.4%) had a clinical history consistent with the Amsterdam criteria for HNPCC. Five (approximately 45%) of 11 of the referral HNPCC case subjects had a mutation in MSH2 or MLH1 and also showed microsatellite instability. The family members of case subjects with mutations tended to show an earlier age at diagnosis of HNPCC and more multiple primary cancers than those of case subjects without detectable mutations. Many of the known characteristics of HNPCC, including the presence of ureteral and endometrial cancers, were seen in both sets of families. The previously reported proximal location of colorectal tumors in HNPCC kindreds was not seen in the population-based dataset but was similar to the location reported in the referral cases. CONCLUSIONS: On the basis of our data, we believe that the prevalence of HNPCC in the general population is likely to be closer to 1% than to 5%. Furthermore, our study suggests that some previously reported characteristics of HNPCC, such as the proximal location of tumors in the syndrome, may not always hold true in a population-based sample.

Myocardial postischemic injury is reduced by polyADPripose polymerase-1 gene disruption.

BACKGROUND: PolyADPribose polymerase (PARP) is activated by DNA strand breaks to catalyze the addition of ADPribose groups to nuclear proteins, especially PARP-1. Excessive polyADPribosylation leads to cell death through depletion of NAD+ and ATP. MATERIALS AND METHODS: In vivo PARP activation in heart tissue slices was assayed through conversion of [33P]NAD+ into polyADPribose (PAR) following ischemia-reperfusion (I/R) and also monitored by immunohistochemical staining for PAR. Cardiac contractility, nitric oxide (NO), reactive oxygen species (ROS), NAD+ and ATP levels were examined in wild type (WT) and in PARP-1 gene-deleted (PARP-1(-/-)) isolated, perfused mouse hearts. Myocardial infarct size was assessed following coronary artery occlusion in rats treated with PARP inhibitors. RESULTS: Ischemia-reperfusion (I/R) augmented formation of nitric oxide, oxygen free radicals and PARP activity. I/R induced decreases in cardiac contractility and NAD+ levels were attenuated in PARP-1(-/-) mouse hearts. PARP inhibitors reduced myocardial infarct size in rats. Residual polyADPribosylation in PARP-1(-/-) hearts may reflect alternative forms of PARP. CONCLUSIONS: PolyADPribosylation from PARP-1 and other sources of enzymatic PAR synthesis is associated with cardiac damage following myocardial ischemia. PARP inhibitors may have therapeutic utility in myocardial disease.

Poly(ADP-ribosyl)ation basally activated by DNA strand breaks reflects glutamate-nitric oxide neurotransmission.

Poly(ADP-ribose) polymerase (PARP) transfers ADP ribose groups from NAD(+) to nuclear proteins after activation by DNA strand breaks. PARP overactivation by massive DNA damage causes cell death via NAD(+) and ATP depletion. Heretofore, PARP has been thought to be inactive under basal physiologic conditions. We now report high basal levels of PARP activity and DNA strand breaks in discrete neuronal populations of the brain, in ventricular ependymal and subependymal cells and in peripheral tissues. In some peripheral tissues, such as skeletal muscle, spleen, heart, and kidney, PARP activity is reduced only partially in mice with PARP-1 gene deletion (PARP-1(-/-)), implicating activity of alternative forms of PARP. Glutamate neurotransmission involving N-methyl-d-aspartate (NMDA) receptors and neuronal nitric oxide synthase (nNOS) activity in part mediates neuronal DNA strand breaks and PARP activity, which are diminished by NMDA antagonists and NOS inhibitors and also diminished in mice with targeted deletion of nNOS gene (nNOS(-/-)). An increase in NAD(+) levels after treatment with NMDA antagonists or NOS inhibitors, as well as in nNOS(-/-) mice, indicates that basal glutamate-PARP activity regulates neuronal energy dynamics.

Purification and properties of cyanide hydratase from Fusarium lateritium and analysis of the corresponding chy1 gene.

The filamentous fungus Fusarium lateritium is cyanide tolerant, due, at least in part, to the induction by cyanide of the enzyme formamide hydrolyase (EC 4.2.1.66). This enzyme, more commonly known as cyanide hydratase, catalyses the hydration of cyanide to formamide. The enzyme was purified from F. lateritium and showed a subunit molecular mass of 43 kDa (as judged by SDS-PAGE), while the native protein appeared to form aggregates of up to 1217 kDa (as judged by gel-filtration and non-denaturing PAGE). mRNA samples from cultures grown with and without cyanide were in vitro translated and immunoprecipitated. This demonstrated that, in this species, the gene encoding the enzyme designated chy1, is cyanide inducible. Differential screening was used to isolate a cyanide hydratase cDNA clone which was subsequently used to obtain the corresponding genomic clone. A fragment of the cDNA clone encoding all but the first seven amino acids of the protein was expressed in E. coli using the expression vector pGEX-2T. Features of F. lateritium cyanide hydratase together with an analysis of the nucleotide sequence encoding this enzyme are presented.

Anaesthesia for laparoscopic cholecystectomy using the Nd:Yag laser. The implications for a district general hospital.

We describe the anaesthetic management of the first reported cholecystectomy by laparoscopic laser in the United Kingdom. The implications of the development of laser surgery in a district general hospital are discussed.

The pressor response and laryngeal mask insertion. A comparison with tracheal intubation.

The pressor response associated with laryngoscopy and tracheal intubation may be harmful to certain patients. The laryngeal mask airway avoids the need for laryngoscopy and allows positive pressure ventilation of the lungs in appropriate patients. This study compared the pressor response of tracheal intubation with that of mask insertion in two groups of 24 and 23 healthy patients respectively. All patients were anaesthetised with thiopentone, nitrous oxide, enflurane and paralysed with atracurium. We have shown a similar, but attenuated pattern of response associated with mask insertion in comparison with laryngoscopy and intubation; significant differences between the groups were evident in arterial diastolic blood pressure immediately after insertion and again 2 minutes later. Use of the laryngeal mask may therefore offer some limited advantages over tracheal intubation in the anaesthetic management of patients where the avoidance of the pressor response is of particular concern.

Incidence of enteric adenoviruses among children in Thailand and the significance of these viruses in gastroenteritis.

In countries with temperate climates, enteric adenoviruses have been shown to be a substantial cause of pediatric gastroenteritis. To determine the incidence of adenovirus infection in a tropical climate, stools were collected from children under age 7 during a 1-year period at an outpatient clinic in Bangkok, Thailand. Stools from 1,114 children with gastroenteritis and from 947 children without gastroenteritis were tested. Each stool was tested for adenovirus group antigen and for specific enteric adenovirus types (Ad40 and Ad41) by monoclonal antibody enzyme immunoassays. We found that 4.4% (49 of 1,114) of children with gastroenteritis and 1.8% (17 of 947) of children without gastroenteritis were positive for adenovirus group antigen. In tests for specific enteric adenovirus types, 2.0% (22 of 1,114) of the tests were positive in children with gastroenteritis and 0.6% (6 of 947) were positive in children without gastroenteritis. There was a significant correlation (P less than 0.02) of gastroenteritis with nonenteric adenovirus types (27 of 1,114) as well as with specific enteric adenovirus types (P less than 0.01). By comparison, 19.7% of children with gastroenteritis and 0.7% of those without gastroenteritis were positive for rotavirus infection. In the adenovirus-infected children with gastroenteritis, there were coinfections with rotavirus only in those with nonenteric adenovirus infection (7 of 27 children). There were no significant differences in the association of bacterial or parasitic infections with either enteric or nonenteric adenovirus infections in either group of children studied. These data demonstrate that Ad40 and Ad41 are causes of gastroenteritis in this population, but among the spectrum of diarrheal etiologies, they may be proportionately less important than they are in countries with temperate climates.

Actin content and organization in normal and transformed cells in culture.

The amount of actin and total protein per cell in normal rat kidney (NRK) cells in culture is initially high in very low density cultures, but rapidly decreases as the cells come into contact in higher density cultures. In a viral transformant of NRK (442), the level of actin and total protein does not change significantly from low to high density cultures. NRK cells, which are flattened against the substrate, have prominent bundles of actinlike microfilaments in the basal cytoplasm adjacent to the substrate. 442 cells, which adhere poorly and are more spherical in shape, lack well-organized basal microfilament bundles, but may display microfilament bundles in cytoplasmic processes extending from the cell body. The percentage of insoluble actin is less than 20% in both cell lines, and 442 cells consistently contain smaller amounts than NRK cells.

Isolation and culture of pulmonary artery endothelial cells.

It has become increasingly evident that endothelial cells function as far more than a mechanical barrier between blood and parenchyma. Endothelial cells from one vesicular bed are known to differ structurally from those of another, and it has been suggested that they may differ functionally. Further to test the hypothesis that endothelial cells from one site may differ in terms of function from those of another site, it is necessary to test endothelium from various source after having obtained these cells in pure, well-characterized cultures. To facilitate such studies, we herein describe in detail means for the isolation, culture and characterization of endothelial cells from calf pulmonary artery. These cells may be of major interest in terms of specific metabolic activities as it has become evident that the lungs play a prominent role in determining the hormonal composition of systemic arterial blood.

Polyamines in Paul's Scarlet rose suspension cultures.

Polyamine concentrations have been determined at intervals in suspension cultures of Paul's Scarlet rose cells during a culture period of 2 weeks. The mean concentrations of the putrescine, spermidine and spermine in the cells of the inocula were respectively 73, 70 and 13 nmol/g fresh weight. Putrescine at fitst increased with a peak (160 nmol/g) after 6 h, declined to a minimum (14 nmol/g) after 2-3 days, increased to a second peak (180 nmol/g) after 5-6 days, and then declined slowly to the concentration of the inoculum (taken on day 14). Spermidine rose slowly (×2.6) to a broad peak over 3-6 days (180 nmol/g), then declined slowly to the concentration in the inoculum. Spermine showed a rapid increase to a peak (130 nmol/g) after 2-3 days, and then declined rapidly, reaching the inoculum concentration by day 6. In one experiment the three amines showed a minor peak at day 11. Changes in spermine and RNA contents appeared to be correlated. DNA content reached a peak after that of the RNA (day 3) and did not appear to be correlated with the content of putrescine or the polyamines.