The Simons Observatory: Cryogenic half wave plate rotation mechanism for the small aperture telescopes.

We present the requirements, design, and evaluation of the cryogenic continuously rotating half-wave plate (CHWP) for the Simons Observatory (SO). SO is a cosmic microwave background polarization experiment at Parque Astronómico de Atacama in northern Chile that covers a wide range of angular scales using both small (⌀0.42 m) and large (⌀6 m) aperture telescopes. In particular, the small aperture telescopes (SATs) focus on large angular scales for primordial B-mode polarization. To this end, the SATs employ a CHWP to modulate the polarization of the incident light at 8 Hz, suppressing atmospheric 1/f noise and mitigating systematic uncertainties that would otherwise arise due to the differential response of detectors sensitive to orthogonal polarizations. The CHWP consists of a 505 mm diameter achromatic sapphire HWP and a cryogenic rotation mechanism, both of which are cooled down to ∼50 K to reduce detector thermal loading. Under normal operation, the HWP is suspended by a superconducting magnetic bearing and rotates with a constant 2 Hz frequency, controlled by an electromagnetic synchronous motor. We find that the number of superconductors and the number of magnets that make up the superconducting magnetic bearing are important design parameters, especially for the rotation mechanism's vibration performance. The rotation angle is detected through an angular encoder with a noise level of 0.07 µrad s. During a cooldown process, the rotor is held in place by a grip-and-release mechanism that serves as both an alignment device and a thermal path. In this paper, we provide an overview of the SO SAT CHWP: its requirements, hardware design, and laboratory performance.

An Open-Source Toolkit To Expand Bioinformatics Training in Infectious Diseases.

As access to high-throughput sequencing technology has increased, the bottleneck in biomedical research has shifted from data generation to data analysis. Here, we describe a modular and extensible framework for didactic instruction in bioinformatics using publicly available RNA sequencing data sets from infectious disease studies, with a focus on host-parasite interactions. We highlight lessons learned from adapting this course for virtual learners during the coronavirus disease 2019 (COVID-19) pandemic.

A trial comparing emergency front of neck airway performance in a novel obese-synthetic neck, meat-modified obese neck and conventional slim manikin.

Conventional emergency front of neck airway training manikins mimic slim patients and are associated with unrealistic procedural ease. We have described previously a pork belly-modified manikin that more realistically simulated an obese patient's neck. In this study, we compared a novel obese-synthetic manikin (obese-synthetic manikin) with a pork belly-modified manikin (obese-meat manikin) and a conventional slim manikin (slim manikin). Thirty-three experienced anaesthetists undertook simulated emergency front of neck airway procedures on each manikin (total 99 procedures). Time to ventilation was longer on both obese manikins compared with the slim manikin (median (IQR [range]) time to intubation 159 (126-243 [73-647]) s in the obese-synthetic, 105 (72-138 [43-279]) s in the obese-meat and 58 (47-74 [30-370]) s in the slim manikin; p < 0.001 between each manikin). Cricothyroidotomy success rate was similar in the both obese manikins but lower when compared with the slim manikin (15/33 obese-synthetic vs. 14/33 obese-meat vs. 27/33 slim manikin). Participant feedback indicated performance difficulty was similar between both obese manikins, which were both more difficult than the slim manikin. The tissues of the obese-meat manikin were judged more realistic than those of either other manikin. Overall, the obese-synthetic manikin performed broadly similarly to the obese-meat manikin and was technically more difficult than the conventional slim manikin. The novel obese-synthetic manikin maybe useful for training and research in front of neck airway procedures.

Sex-Specific Gene Expression Differences Are Evident in Human Embryonic Stem Cells and During In Vitro Differentiation of Human Placental Progenitor Cells.

The placenta is a short-lived tissue required for embryonic growth and survival, and it is fetal derived. Fetal sex influences gestation, and many sexual dimorphic diseases have origins in utero. There is sex-biased gene expression in third-trimester human placentas, yet the origin of sex-specific expression is unknown. Here, we used an in vitro differentiation model to convert human embryonic stem cells (hESCs) into trophoblastic progenitor cells of the first-trimester placenta, which will eventually become mature extravillous trophoblasts and syncytiotrophoblasts. We observed significant sex differences in transcriptomic profiles of hESCs and trophoblastic progenitors, and also with the differentiation process itself. Male cells had higher dosage of X/Y gene pairs relative to female samples, supporting functions for Y-linked genes beyond spermatogenesis in the hESCs and in the early placenta. Female-specific differentiation altered the expression of several thousand genes compared with male cells, and female cells specifically upregulated numerous autosomal genes with known roles in trophoblast function. Sex-biased upregulation of cellular pathways during trophoblast differentiation was also evident. This study is the first to identify sex differences in trophoblastic progenitor cells of the first-trimester human placenta, and reveal early origins for sexual dimorphism.

PI 3-kinase and MAP kinase regulate bradykinin induced prostaglandin E(2) release in human pulmonary artery by modulating COX-2 activity.

Here we studied the role of phosphoinositide 3-kinase (PI 3-kinase) and mitogen activated protein (MAP) kinase in regulating bradykinin (BK) induced prostaglandin E(2) (PGE(2)) production in human pulmonary artery smooth muscle cells (HPASMC). BK increased PGE(2) in a three step process involving phospholipase A(2) (PLA(2)), cyclooxygenase (COX) and PGE synthase (PGES). BK stimulated PGE(2) release in cultured HPASMC was inhibited by the PI 3-kinase inhibitor LY294002 and the p38 MAP kinase inhibitor SB202190. The inhibitory mechanism used by LY294002 did not involve cytosolic PLA(2) activation or COX-1, COX-2 and PGES protein expression but rather a novel effect on COX enzymatic activity. SB202190 also inhibited COX activity.

Effect of bradykinin, TGF-beta1, IL-1beta, and hypoxia on COX-2 expression in pulmonary artery smooth muscle cells.

Prostanoids are major regulators of smooth muscle function that are generated by cyclooxygenase (COX). Here we hypothesized that cytokines and mediators that regulate the pulmonary circulation would alter COX expression and prostanoid generation in pulmonary artery smooth muscle cells. Bradykinin, transforming growth factor-beta1 (TGF-beta1), and interleukin-1beta (IL-1beta) increased inducible COX-2 expression and prostaglandin E(2) (PGE(2)) release. Transfection studies using a COX-2 promoter construct demonstrated that all three agents acted transcriptionally. Constitutive COX-1 protein expression was unchanged. The COX inhibitor indomethacin, the COX-2 inhibitor NS-398, the protein synthesis inhibitor cycloheximide, and the glucocorticoid dexamethasone abrogated the increased PGE(2) levels. Dexamethasone and cycloheximide prevented COX-2 induction. Hypoxia (3% O(2)-5% CO(2)-92% N(2)) for 24 h selectively augmented TGF-beta1-stimulated PGE(2) production and COX-2 induction but had no effect alone. Prolonged hypoxic culture alone for 48 and 72 h enhanced COX-2 induction and increased PGE(2). These studies show that a number of stimuli are capable of inducing COX-2 in pulmonary artery smooth muscle cells. The interaction between hypoxia and TGF-beta1 may be particularly relevant to pulmonary hypertension.

Human airway smooth muscle cells secrete vascular endothelial growth factor: up-regulation by bradykinin via a protein kinase C and prostanoid-dependent mechanism.

Bronchial vascular remodeling is an important feature of the pathology of chronic asthma, but the responsible mechanisms and main sources of angiogenic factors are unclear. Here we report that human airway smooth muscle cells express vascular endothelial growth factor (VEGF)121, 165, 189, 206 splice variants and secrete VEGF protein constitutively. VEGF protein secretion was increased by the proinflammatory asthma mediator bradykinin through post-transcriptional mechanisms. Bradykinin-induced VEGF secretion was dependent on the B2 bradykinin receptor, activation of protein kinase C, and generation of endogenous prostanoids. This is the first report that bradykinin can increase VEGF secretion in any biological system and the first to show that airway smooth muscle cells produce VEGF. Our results suggest a novel role for human airway smooth muscle in contributing to bronchial mucosal angiogenesis in chronic asthma by secretion of VEGF and suggest a wider role for mesenchymal cell products in mediating angiogenesis in inflammatory and allergic diseases.

Sentinel lymph node biopsy for melanoma: experience with 234 consecutive procedures.

Sentinel lymph node biopsy is increasingly used to identify occult metastases in regional lymph nodes of patients with melanoma. Selection of patients for sentinel lymph node biopsy and subsequent lymphadenectomy is an area of debate. The purpose of this study was to describe a large clinical series of these biopsies for cutaneous melanoma and to identify patients most likely to gain useful clinical information from sentinel lymph node biopsy. The Indiana University Melanoma Program computerized database was queried to identify all patients who underwent this procedure for clinically localized cutaneous melanoma. It was performed using preoperative technetium Tc 99m lymphoscintigraphy and isosulfan blue dye. Pertinent demographic, surgical, and histopathologic data were recorded. Univariate and multivariate logistic regression and classification table analyses were performed to identify clinical variables associated with sentinel node and nonsentinel node positivity. In total, 234 biopsy procedures were performed to stage 291 nonpalpable regional lymph node basins. Mean Breslow's thickness was 2.30 mm (2.08 mm for negative sentinel lymph node biopsy, 3.18 mm for positive). The mean number of sentinel nodes removed was 2.17 nodes per basin (range, 1 to 8). Forty-seven of 234 melanomas (20.1 percent) and 50 of 291 basins (17.2 percent) had a positive biopsy. Positivity correlated with AJCC tumor stage: T1, 3.6 percent; T2, 8.1 percent; T3, 27.4 percent; T4, 44 percent. By univariate logistic regression, Breslow's thickness (p = 0.003, continuous variable), ulceration (p = 0.003), mitotic index > or = 6 mitoses per high power field (p = 0.008), and Clark's level (p = 0.04) were significantly associated with sentinel lymph node biopsy result. By multivariate analysis, only Breslow's thickness (p = 0.02), tumor ulceration (p = 0.02), and mitotic index (p = 0.02) were significant predictors of biopsy positivity. Classification table analysis showed the Breslow cutpoint of 1.2 mm to be the most efficient cutpoint for sentinel lymph node biopsy result (p = 0.0004). Completion lymphadenectomy was performed in 46 sentinel node-positive patients; 12 (26.1 percent) had at least one additional positive nonsentinel node. Nonsentinel node positivity was marginally associated with the presence of multiple positive sentinel nodes (p = 0.07). At mean follow-up of 13.8 months, four of 241 sentinel node-negative basins demonstrated same-basin recurrence (1.7 percent). Sentinel lymph node biopsy is highly reliable in experienced hands but is a low-yield procedure in most thin melanomas. Patients with melanomas thicker than 1.2 mm or with ulcerated or high mitotic index lesions are most likely to have occult lymph node metastases by sentinel lymph node biopsy. Completion therapeutic lymphadenectomy is recommended after positive biopsy because it is difficult to predict the presence of positive nonsentinel nodes.

DNA structure specificity of Rap endonuclease.

The Rap protein of phage lambda is an endonuclease that nicks branched DNA structures. It has been proposed that Rap can nick D-loops formed during phage recombination to generate splice products without the need for the formation of a 4-strand (Holliday) junction. The structure specificity of Rap was investigated using a variety of branched DNA molecules made by annealing partially complementary oligo-nucleotides. On Holliday junctions, Rap endonuclease shows a requirement for magnesium or manganese ions, with Mn(2+)supporting 5-fold more cleavage than Mg(2+). The location of endonuclease incisions was determined on 3'-tailed D-loop, bubble, flayed duplex, 5'-flap and Y junction DNA substrates. In all cases, Rap preferentially cleaves at the branch point of these molecules. With a flayed duplex, incisions are made in the duplex adjacent to the single-strand arms. Comparison of binding and cleavage specificities revealed that Rap is highly structure-specific and exhibits a clear preference for 4- and 3-stranded DNA over Y and flayed duplex DNA. Almost no binding or cleavage was detected with duplex, partial duplex and single-stranded DNA. Thus Rap endonuclease shows a bias for structures that resemble D-loop and Holliday junction recombination intermediates.

lambda Rap protein is a structure-specific endonuclease involved in phage recombination.

Bacteriophage lambda encodes a number of genes involved in the recombinational repair of DNA double-strand breaks. The product of one of these genes, rap, has been purified. Truncated Rap proteins that copurify with the full-length form are derived, at least in part, from a rho-dependent transcription terminator located within its coding sequence. Full-length and certain truncated Rap polypeptides bind preferentially to branched DNA substrates, including synthetic Holliday junctions and D-loops. In the presence of manganese ions, Rap acts as an endonuclease that cleaves at the branch point of Holliday and D-loop substrates. It shows no obvious sequence preference or symmetry of cleavage on a Holliday junction. The biochemical analysis of Rap gives an insight into how recombinants could be generated by the nicking of a D-loop without the formation of a classical Holliday junction.

Seasonal activity and energetics of two species of varanid lizards in tropical Australia.

The field metabolic rates (FMR) and rates of water flux were measured in two species of varanid lizards over five periods of the year in tropical Australia. The energetics of these species were further investigated by directly measuring activity (locomotion) and body temperatures of free-ranging animals by radiotelemetry, and by measuring standard metabolic rate (over a range of body temperatures) and activity metabolism in the laboratory. Seasonal differences in the activity and energetics were found in these goannas despite similar, high daytime temperatures throughout the year in tropical Australia. Periods of inactivity were associated with the dry times of the year, but the onset of this period of inactivity differed with respect to habitat even within the same species. Varanus gouldii, which inhabit woodlands only, were inactive during the dry and late dry seasons. V. panoptes that live in the woodland had a similar seasonal pattern of activity, but V. panoptes living near the floodplain of the South Alligator River had their highest levels of activity during the dry season when they walked long distances to forage at the receding edge of the floodplain. However, during the late dry season, after the floodplain had dried completely, they too became inactive. For V. gouldii, the rates of energy expenditure were 196 kJ kg-1 day-1 for active animals and 66 kJ kg-1 day-1 for inactive animals. The rates of water influx for these groups were respectively 50.7 and 19.5 ml kg-1 day-1. For V. panoptes, the rates of energy expenditure were 143 kJ kg-1 day-1 for active animals and 56 kJ kg-1 day-1 for inactive animals. The rates of water influx for these two groups were respectively 41.4 and 21.0 ml kg-1 day-1. We divided the daily energy expenditure into the proportion of energy that lizards used when "in burrows", "out of burrows but inactive", and "in locomotion" for the two species during the different seasons. The time spent in locomotion by V. panoptes during the dry season is extremely high for a reptile (mean of 3.5 h/day spent walking), and these results provide an ecological correlate to the high aerobic capacity found in laboratory measurements of some species of varanids.

Long term results with 2'deoxycoformycin in hairy cell leukemia.

We have treated 159 patients with hairy cell leukemia (HCL) with 2'deoxycoformycin (DCF) in a phase II study that started in 1986. 151 patients had typical HCL and 8 HCL-variant. Ages ranged from 30 to 81 years. Most patients had previously received interferon-alpha, splenectomy or both and 23 had DCF as first line; all had active disease. In the first 40 patients DCF was given at 4 mg/m2 weekly for 4 weeks and every 2 weeks thereafter and in the remainder every 2 weeks until maximal response. Three patients died early on and were non-evaluable for response. The response rates in 148 patients with typical HCL were: CR 74.3%, PR 22.3% and NR 3.4%. None of the HCL-variants achieved CR; 4 had PR and 4 NR. The median number of DCF injections to CR was 9. Lymphopenia and neutropenia were seen in 52% and 34%, respectively, but 72% of patients started treatment with low leucocyte counts. 27% had infectious complications of which 6% were life threatening. The disease free interval of the first 105 remitters (CR + PR) was 84% at 4 years with no significant difference between CR (86%) and PR (77%). There have been 12 relapses at a median time of 22 months (range 6-60 months) since stopping DCF, of these, 5 had massive abdominal lymphadenopathy, a features seen also in 4 of the 5 primary non-responders. There were 13 deaths but 7 were unrelated to HCL. The 5-year survival from starting DCF in 110 patients with typical HCL was 88% and 97% if we exclude non-HCL deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

An experimental test of the muscle tension hypothesis of tension-type headache.

The present study employed an experimental design to provide a direct test of the classic etiological account of tension-type headaches, that these stem from elevated levels of muscle tension. Twenty-eight female subjects with relatively frequent headaches were divided into 4 groups, according to a 2 x 2 design. The independent variables were (1) Target response (to maintain elevated levels of either frontalis EMG or digital temperature for 40 min), and (2) Expectation (either specifically of a headache or of some unspecified discomfort). Dependent variables included headache as well as a number of other possible symptoms. Results showed that subjects were successful in complying with their assigned tasks. However, there were no main effects of Target response or Expectation and no interactions of these factors with respect to headache or any other symptom. These data provide strong evidence against the classic etiological account of muscle-contraction headaches.

The acute geriatric psychiatry service: a suggested model.

In general hospitals, especially on acute medical-surgical, and general psychiatric units, geriatric patients are often exposed to attitudes of resentment or rejection. Individuals with treatable mental illnesses may be relatively neglected or dismissed as "senile," and their special needs not attended to. This tends to occur when the particular psychological issues of elderly patients are not shared by most of the other patients, and also when staff members are prejudiced about old people, either because of fear about their own aging or because of unresolved difficulties with parents or grandparents. The authors believe that age-specific geriatric units are the most effective treatment format for the elderly in need of psychiatric care. One example of such a unit opened in 1980, the Geriatric Psychiatry Unit currently in operation at the Johnston R. Bowman Health Center for the Elderly, a part of Rush-Presbyterian-St. Luke's Medical Center in Chicago, is described.

Recurrent hemoperitoneum in women receiving continuous ambulatory peritoneal dialysis.

Of 27 women in the reproductive age group receiving continuous ambulatory peritoneal dialysis for more than 3 months, 4 of 7 who menstruated developed recurrent hemoperitoneum. Tubal ligation had been done in 3 of these 4 women. There were 37 episodes of hemoperitoneum; 22 occurred at midcycle and 15 with menstruation. One patient required repeated blood transfusion, but after oral anovulant therapy no further bleeding occurred and no transfusion was required. Two patients needed laparotomy: one for heavy intraperitoneal bleeding originating from a luteal cyst, and the other for severe lower abdominal pain from follicular and luteal cysts. Ultrasound examinations suggested the presence of small ovarian cysts in the two remaining patients. Recurrent midcycle hemoperitoneum in women on continuous ambulatory peritoneal dialysis may be triggered by ovulation and associated ovarian cyst formation. Suppression of ovulation should be considered.

The feeding ecology of the dingo : III. Dietary relationships with widely fluctuating prey populations in arid Australia: an hypothesis of alternation of predation.

Changes in the diet of dingoes (Canis familiaris dingo) in response to measured fluctuations of prey populations were followed over 7 years. The study began after great rains had broken a long drought. Eruptions of rodents and rabbits followed, but some prey were always either relatively abundant (live cattle) or scarce (red kangaroo, lizards, birds). Cattle carcasses were increasingly available during a subsequent drought. Small and medium-sized prey, rodents (26%), lizards (12%) and rabbits (56%) were preferred, probably because they were easily caught. Only rabbits were caten consistently regardless of density. By contrast, large prey were eaten in relatively large amounts only during drought, with initial emphasis on red kangaroos (15% overall) and then cattle (17%) mostly as carcasses. The diet was functionally related to the respective abundances of all major prey species, but the relationship shifted during drought when predation on low populations was most severe. There was evidence that growth of resurging prey populations were suppressed by predation. Diets of dingoes did not differ significantly with age or sex. An hypothesis of 'alternation of predation' is presented: dingoes feed sequentially on prey of increasing size (rodents, rabbits, red kangaroos, cattle) in response to rainy periods and subsequent droughts, meanwhile always concentrating on the staple prey (rabbits). The fluctuating abundances of small and medium-sized prey determined not only their own relative availabilities but also that of large prey, and hence determined the diet of the dingo at any time. Prey availability (catchability, accessability) appeared to be more important than prey abundance (numbers, biomass), and the dingo's flexible social organisation allowed versatility in hunting strategies and defence of resources. We conclude that dingoes do not always forage most efficiently as optimal foraging models predict because of the constraints imposed by the capricious environment in arid Australis, where prey availability fluctuates greatly and becomes limited and clumped in drought, so that dingoes may be faced with outright starvation. Instead we conclude that dingoes utilise a conservative feeding strategy and adopt any behaviour which provides at least a threshold quantity of energy or nutrient as part of a trade-off with other competing ecological requirements.

Helminth parasites of wild cats in north-east Scotland.

Three cestode species, namely Taenia taeniaeformis Batsch, 1786, Taenia pisiformis (Bloch, 1780) and Mesocestoides litteratus (Batsch, 1786) and one nematode species, Toxocara cati Schrank, 1788, were found in wild cats collected in Grampian region, Scotland. Of the 41 cats examined, 25 were Felis silvestris, 12 were feral Felis catus and four were hybrids of F. silvestris and F. catus.