Tunable Coupling Architecture for Fixed-Frequency Transmon Superconducting Qubits.

Implementation of high-fidelity 2-qubit operations is a key ingredient for scalable quantum error correction. In superconducting qubit architectures, tunable buses have been explored as a means to higher-fidelity gates. However, these buses introduce new pathways for leakage. Here we present a modified tunable bus architecture appropriate for fixed-frequency qubits in which the adiabaticity restrictions on gate speed are reduced. We characterize this coupler on a range of 2-qubit devices, achieving a maximum gate fidelity of 99.85%. We further show the calibration is stable over one day.

Global distribution of white spot syndrome virus genotypes determined using a novel genotyping assay.

White spot disease, caused by infection with white spot syndrome virus (WSSV), is a serious panzootic affecting prawn aquaculture. The disease has spread rapidly around the prawn-culturing regions of the world through a number of previously identified mechanisms. The ability to distinguish and trace strains of WSSV is of great benefit to identify, and then limit, the translocation routes of the disease. Here, we describe a novel genotyping method using 34 short tandem repeat regions of the viral genome concurrently. This technique is highly sensitive to strain differences when compared to previous methods. The efficacy of the described method is demonstrated by testing WSSV isolates from around the globe, showing regional genotypic differences. The differences in the genotypes were used to create a global minimum spanning network, and in most cases the observed relationships were substantiated with verification of transboundary movement. This novel panel of STR markers will provide a valuable epidemiological tool for white spot disease. We have applied this to an outbreak of the disease in Queensland, Australia, that occurred in 2016. While the results indicate that the source of this outbreak currently remains cryptic, the analyses have provided valuable insights with which to further study the origins of the strains involved.

Photonic ring resonator filters for astronomical OH suppression.

Ring resonators provide a means of filtering specific wavelengths from a waveguide, and optionally dropping the filtered wavelengths into a second waveguide. Both of these features are potentially useful for astronomical instruments. In this paper we focus on their use as notch filters to remove the signal from atmospheric OH emission lines from astronomical spectra. We derive the design requirements for ring resonators for OH suppression from theory and finite difference time domain simulations. We find that rings with small radii (< 10 µm) are required to provide an adequate free spectral range, leading to high index contrast materials such as Si and Si3N4. Critically coupled rings with high self-coupling coefficients should provide the necessary Q factors, suppression depth, and throughput for efficient OH suppression, but will require post-inscription tuning of the coupling and the resonant wavelengths. The overall prospects for the use of ring resonators in astronomical instruments is promising, provided efficient fibre-chip coupling can be achieved.

Mu-opioid receptor knockout on Foxp2-expressing neurons leads to reduced aversion-resistant reward seeking.

Mu-opioid receptors (MORs) in the amygdala and striatum are important in addictive and rewarding behaviors. Foxp2 is a marker of intercalated (ITC) cells in the amygdala and a subset of striatal medium spiny neurons (MSNs), both of which express MORs in wild-type mice. For the current series of studies, we characterized the behavior of mice with genetic deletion of the MOR gene Oprm1 in Foxp2-expressing neurons (Foxp2-Cre/Oprm1 fl/fl ). Male and female Foxp2-Cre/Oprm1 fl/fl mice were generated and heterozygous Cre+ (knockout) and homozygous Cre-(control) animals were tested for aversion-resistant alcohol consumption using an intermittent access (IA) task, operant responding for a sucrose reward, conditioned place aversion (CPA) to morphine withdrawal, and locomotor sensitization to morphine. In IA, mice with the MOR-knockout were more sensitive to quinine-adulterated ethanol (EtOH) and less aversion-resistant, as they decreased EtOH consumption from baseline at all quinine concentrations, while control animals did not. In operant conditioning, Cre+ mice similarly exhibited less aversion-resistant reward seeking than Cre-mice when sucrose was adulterated with quinine. For CPA, both control and MOR-knockout mice demonstrated withdrawal-induced aversion. For locomotor sensitization, Cre+ mice demonstrated decreased locomotion following morphine injection compared to Cre-mice. The results of these studies suggest that MOR expression on Foxp2-expressing neurons is not necessary for rewarded behaviors or expression of opioid withdrawal but may be involved in aversion-resistance.

Investigation into white spots in the carapace of a moribund mud crab (Scylla serrata) from a white spot syndrome virus (WSSV) positive zone in Moreton Bay, Australia.

BACKGROUND: A freshly deceased mud crab (Scylla serrata) exhibiting multiple white spots under the carapace was found in Pumicestone Passage, northern Moreton Bay in May 2018. This crab was taken from within a biosecurity zone established due to a recent incursion of White Spot Syndrome Virus (WSSV) into populations of wild penaeids (Penaeus spp., Metapenaeus spp.) and crabs (Thalamita crenata) in the area. Because grossly visible white spots have been previously observed under the carapace of moribund S. serrata with white spot disease (WSD) in India, an investigation into the cause of death was undertaken. CASE REPORT: The affected S. serrata was negative for WSSV DNA when gill samples were tested by real-time PCR. Histopathology found no evidence of WSD lesions in the form of basophilic hypertrophied intranuclear inclusions in any tissues of ectodermal or mesodermal origin. Histopathology of the affected carapace showed that the white spots consisted of multiple lighter coloured foci in the exocuticle formed from concentric crystalline-like rings, which extended into the endocuticle. These were interpreted as evidence of mineral mobilisation within the carapace during the pre-moult (D1 or D2) stage of the moult cycle. The cause of death in this case therefore may have been due to moult-related complications. CONCLUSION: These observations confirm that formation of grossly visible white spots under the carapace of S. serrata are not pathognomonic for infection with WSSV. Similar observations in previous studies where WSSV was detected by PCR in this same host may have been incidental findings.

Silk gland-specific tRNA(Ala) genes are tightly clustered in the silkworm genome.

To understand the basis for tissue-specific production and accumulation of alanine tRNA in silkworms, we have examined the organization of the genes that code for silk gland-specific and constitutive alanine tRNAs. We have found that all of the silk gland-specific tRNA(Ala) genes (approximately 20) appear to be tightly clustered at a single locus in the Bombyx genome. These genes are arranged in tandem at intervals of approximately 150 base pairs. In contrast to the arrangement of the silk gland-specific tRNA(Ala) genes, most of the 20 to 30 constitutive tRNA(Ala) genes are dispersed in the genome. Silk gland-specific tRNA(Ala) genes are not amplified or grossly rearranged in the silk gland. Thus it is likely that differential transcription, rather than changes in gene number or structure, accounts for the tissue-specific accumulation of tRNA(Ala).

Myocardial infarction and normal coronary arteriography: a 10 year clinical and risk analysis of 74 patients.

Myocardial infarction with normal coronary arteries was identified in 74 patients with a mean age of 43 years (range 19 to 66). A mean follow-up period of 10.5 years after documented myocardial infarction and 8.6 years after cardiac catheterization was obtained. The survival rate was 85% (n = 63). There were no statistical differences in age or clinical risk factor prevalence between survivors and nonsurvivors. Moderate (55%) to severe (27%) left ventricular impairment was more common in nonsurvivors. Nine of 11 deaths were cardiovascular, 6 were sudden and 8 occurred in patients with moderate to severe global left ventricular impairment. Seventy-six percent of survivors were asymptomatic and 86% were fully active at follow-up. Two survivors and three nonsurvivors experienced a second myocardial infarction. The clinical risk factors of the study group (Group I) were compared by age, sex and year of catheterization with risk factors in two matched groups. Group II consisted of 74 patients with coronary occlusive disease and myocardial infarction and Group III consisted of 148 patients with normal arteriograms. Group I differed from Group II in having fewer clinical risk factors (p = 0.01 to less than 0.0001). Cigarette smoking did not differ significantly between Group I (72%) and Group II (69%) but was less common in Group III (45%) (p less than 0.001). Hormone therapy or the peripartum state was more common in women in Group I (34%) than in women in Group III (14%) (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence and prognostic significance of intraventricular conduction abnormalities after coronary bypass surgery.

To determine the incidence and prognostic significance of new postoperative conduction disturbances, 2,000 consecutive patients who underwent primary elective coronary bypass surgery were evaluated. One hundred eleven (5.5%) of the 2,000 patients developed a new intraventricular conduction defect that persisted to hospital discharge. Right bundle branch block occurred in 86 (85%), left bundle branch block in 5 (4%) and nonspecific intraventricular conduction defect in 9 (11%). One hundred of these 111 patients were successfully matched with others in the study population who had maintained normal intraventricular conduction during the operative period. Patients were matched on the basis of age, gender, absence of preoperative conduction disturbances, left ventricular function and bypass grafts to the same vessels. Follow-up of the two groups for a period of 1 to 76 months (mean 60 months) failed to show any difference in survival or cardiac events such as myocardial infarction, repeat coronary bypass surgery, coronary angioplasty and permanent pacemaker implantation. The appearance of right or left bundle branch block or a nonspecific intraventricular conduction defect after coronary bypass surgery does not appear to have an unfavorable impact on the long-term prognosis of these patients.

Videodensitometric ejection fraction from intravenous digital subtraction right ventriculograms: correlation with first pass radionuclide ejection fraction.

Thirty-one consecutive patients undergoing intravenous blurred mask digital subtraction right ventriculography were submitted to first pass radionuclide angiography. Second order mask resubtraction of end-diastolic and end-systolic right ventricular digital image frames was executed using preinjection end-diastolic and end-systolic frames to rid the digital subtraction images of mis-registration artifact. End-diastolic and end-systolic perimeters were drawn manually by two independent observers with a light pen. Ejection fractions calculated from the integrated videodensitometric counts within these perimeters correlated well with those derived from the first pass radionuclide right ventriculogram (r = 0.84) and the interobserver correlation was acceptable (r = 0.91). Interobserver differences occurred more frequently in patients with atrial fibrillation and in those whose tricuspid valve planes were difficult to discern on the digital subtraction right ventriculograms. These results suggest that videodensitometric analysis of digital subtraction right ventriculograms is an accurate method of determining right ventricular ejection fraction and may find wide clinical applicability.

Acute myocardial infarction and complete bundle branch block at hospital admission: clinical characteristics and outcome in the thrombolytic era. GUSTO-I Investigators. Global Utilization of Streptokinase and t-PA [tissue-type plasminogen activator] for Occluded Coronary Arteries.

OBJECTIVES: We sought to assess the outcome of patients with acute myocardial infarction (MI) and bundle branch block in the thrombolytic era. BACKGROUND: Studies of patients with acute MI and bundle branch block have reported high mortality rates and poor overall prognosis. METHODS: The North American population with acute MI and bundle branch block enrolled in the Global Utilization of Streptokinase and t-PA [tissue-type plasminogen activator] for Occluded Coronary Arteries (GUSTO-I) trial was matched by age and Killip class with an equal number of GUSTO-I patients without conduction defects. RESULTS: Of all 26,003 North American patients in GUSTO-I, 420 (1.6%) had left (n = 131) or right (n = 289) bundle branch block. These patients had higher 30-day mortality rates than matched control subjects (18% vs. 11%, p = 0.003, odds ratio [OR] 1.8) and were more likely to experience cardiogenic shock (19% vs. 11%, p = 0.008, OR 1.78) or atrioventricular block/asystole (30% vs. 19%, p < 0.012, OR 1.57) and to require ventricular pacing (18% vs. 11%, p = 0.006, OR 1.73). Bundle branch block also carried an independent 53% higher risk for 30-day mortality. Thirty-day mortality rates for patients with complete, partial and no reversion of the bundle branch block were 8%, 12% and 20%, respectively (two-tailed chi-square test for trend 5.61, p = 0.02, OR 0.34 for complete reversion, OR 0.55 for partial reversion). CONCLUSIONS: Bundle branch block at hospital admission in patients with acute MI predicts in-hospital complications and poor short-term survival.

Getting it together: signal transduction in G-protein coupled receptors by association of receptor domains.

The mechanism of signal transduction by G-protein coupled receptors is unknown. Here, we propose that these receptors signal in a way that is qualitatively similar to that seen in the chemokine and endocrine hormone receptor families; the signal occurs when two domains of the receptor are brought together, although this is not the only requirement for signaling.

Structural model of antagonist and agonist binding to the angiotensin II, AT1 subtype, G protein coupled receptor.

BACKGROUND: The family of G protein coupled receptors is the largest and perhaps most functionally diverse class of cell-surface receptors. Due to the difficulty of obtaining structural data on membrane proteins there is little information on which to base an understanding of ligand structure-activity relationships, the effects of receptor mutations and the mechanism(s) of signal transduction in this family. We therefore set out to develop a structural model for one such receptor, the human angiotensin II receptor. RESULTS: An alignment between the human angiotensin II (type 1; hAT1), human beta 2 adrenergic, human neurokinin-1, and human bradykinin receptors, all of which are G protein coupled receptors, was used to generate a three-dimensional model of the hAT1 receptor based on bacteriorhodopsin. We observed a region within the model that was congruent with the biogenic amine binding site of beta 2, and were thus able to dock a model of the hAT1 antagonist L-158,282 (MK-996) into the transmembrane region of the receptor model. The antagonist was oriented within the helical domain by recognising that the essential acid functionality of this antagonist interacts with Lys199. The structural model is consistent with much of the information on structure-activity relationships for both non-peptide and peptide ligands. CONCLUSIONS: Our model provides an explanation for the conversion of the antagonist L-158,282 (MK-996) to an agonist by the addition of an isobutyl group. It also suggests a model for domain motion during signal transduction. The approach of independently deriving three-dimensional receptor models and pharmacophore models of the ligands, then combining them, is a powerful technique which helps validate both models.

Structural requirements for the activation of the human growth hormone secretagogue receptor by peptide and nonpeptide secretagogues.

Antibodies raised against an intracellular and extracellular domain of the GH secretagogue receptor (GHS-R) confirmed that its topological orientation in the lipid bilayer is as predicted for G protein-coupled receptors with seven transmembrane domains. A strategy for mapping the agonist-binding site of the human GHS-R was conceived based on our understanding of ligand binding in biogenic amine and peptide hormone G protein-coupled receptors. Using site-directed mutagenesis and molecular modeling, we classified GHS peptide and nonpeptide agonist binding in the context of its receptor environment. All peptide and nonpeptide ligand classes shared a common binding domain in transmembrane (TM) region 3 of the GHS-R. This finding was based on TM-3 mutation E124Q, which eliminated the counter-ion to the shared basic N+ group of all GHSs and resulted in a nonfunctional receptor. Restoration of function for the E124Q mutant was achieved by a complementary change in the MK-0677 ligand through modification of its amine side-chain to the corresponding alcohol. Contacts in other TM domains [TM-2 (D99N), TM-5 (M213K, S117A), TM-6 (H280F), and extracellular loop 1 (C116A)] of the receptor revealed specificity for the different peptide, benzolactam, and spiroindolane GHSs. GHS-R agonism, therefore, does not require identical disposition of all agonist classes at the ligand-binding site. Our results support the hypothesis that the ligand-binding pocket in the GHS-R is spatially disposed similarly to the well characterized catechol-binding site in the beta2-adrenergic receptor.

Inhibition of human leukocyte elastase. 2. Inhibition by substituted cephalosporin esters and amides.

A variety of 7 alpha-methoxycephalosporin ester and amide sulfones were prepared and tested to determine the structure-activity relations for inhibition of human leukocyte elastase (HLE), a serine protease which has been implicated in several degenerative lung and tissue diseases. The most potent IC50 values were obtained with neutral, lipophilic derivatives, with the esters being more active than the amides. However, the best time-dependent inhibition in this series was observed with the p- and m-carboxybenzyl esters 7b and 7c. These results are discussed in terms of the proposed mechanism of inhibition as well as a molecular modeling study using the recently solved X-ray crystal structure of HLE.

1,4-Cyclohexanecarboxylates: potent and selective inhibitors of phosophodiesterase 4 for the treatment of asthma.

Evaluation of a variety of PDE4 inhibitors in a series of cellular and in vivo assays suggested a strategy to improve the therapeutic index of PDE4 inhibitors by increasing their selectivity for the ability to inhibit PDE4 catalytic activity versus the ability to compete for high affinity [3H]rolipram-binding sites in the central nervous system. Use of this strategy led ultimately to the identification of cis-4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexane-1-carboxyl ic acid (1, SB 207499, Ariflo), a potent second-generation inhibitor of PDE4 with a decreased potential for side effects versus the archetypic first generation inhibitor, (R)-rolipram.

Ineffectiveness of dipyridamole SPECT thallium imaging as a screening technique for coronary artery disease in patients with end-stage renal failure.

The efficacy of dipyridamole single photon emission computed tomography (SPECT) thallium as a screening test for coronary artery disease (CAD), was studied in 45 patients with end-stage renal failure undergoing evaluation for renal transplantation. Coronary arteriography, dipyridamole SPECT thallium imaging and clinical follow-up were performed in all patients. Nineteen patients (42%) had an obstruction of 50% or more in at least one coronary artery. Fourteen patients had a positive thallium scan, but 7 of these were false-positives (sensitivity 37%, specificity 73%). The sensitivity was considerably lower than that quoted for non-ESRF patients in the literature, and significantly lower than a control group of 19 patients without ESRF having comparable severity and distribution of CAD. Five of the 6 patients who died of cardiac causes over a mean follow-up period of 25 months had normal thallium imaging, but all had significant coronary artery disease at cardiac catheterization. Dipyridamole SPECT thallium imaging has not proved a useful screening test for angiographically significant CAD, and does not predict cardiac prognosis in this population.

Influence of left ventricular mass on the diagnostic accuracy of myocardial perfusion imaging using positron emission tomography with dipyridamole stress.

This study assesses the influence of left ventricular hypertrophy (LVH) on the accuracy of myocardial perfusion imaging using pharmacologic coronary vasodilation. Seventy-five patients without previous infarction, and with known coronary anatomy, were studied by echocardiography and PET. LVH (defined by mass greater than 131 g/m2 in males or greater than 100 g/m2 in females) was identified in 25 patients; this group did not differ significantly from the remainder in terms of clinical or angiographic parameters. Twenty patients with hypertrophy had significant coronary artery stenoses, which were identified correctly by PET in 11 (55%), in contrast to 29 of 34 patients (85%, p = 0.03) with coronary disease but normal LV mass. Normal perfusion images were obtained in three of five patients (60%) with hypertrophy but no coronary disease; in contrast, 14 of 16 patients without either coronary disease or hypertrophy (88%, p = ns) had normal scans. The accuracy of PET was 14/25 (56%) in those with hypertrophy, and 43/50 (86%, p = 0.01) in patients with normal LV mass. In this group, the presence of hypertrophy was associated with reduction in the diagnostic accuracy of PET using dipyridamole stress. These findings may account for the phenomenon of "dipyridamole nonresponsiveness" in some patients.

A prospective comparison of rubidium-82 PET and thallium-201 SPECT myocardial perfusion imaging utilizing a single dipyridamole stress in the diagnosis of coronary artery disease.

The purpose of the present study is to prospectively compare myocardial perfusion imaging with rubidium-82 (82Rb) by positron emission tomography (PET) with thallium-201 (201Tl) imaging by single-photon emission tomography (SPECT) by recording both studies with a single dipyridamole handgrip stress, and reading both sets of images with the same display technique. In a series of 202 patients with previous coronary arteriography, the sensitivity, specificity, and accuracy of 82Rb PET were 93%, 78%, and 90% and for 201Tl SPECT 76%, 80%, and 77%, respectively. When 70 patients with previous therapeutic interventions were excluded, the remaining 132 patients showed a sensitivity, specificity, and accuracy of 95%, 82% and 92% for 82Rb PET and 79%, 76%, and 78% for 201Tl SPECT. The improved contrast resolution of PET resulted in markedly superior images and a more confident identification of defects.

Clinical evaluation of 360 degrees and 180 degrees data sampling techniques for transaxial SPECT thallium-201 myocardial perfusion imaging.

The most serious controversy regarding the application of transaxial SPECT technology to 201Tl myocardial perfusion imaging is the choice between 360 degrees compared with 180 degrees data sampling techniques. The present study utilized the original 360 degrees sampled raw data of 25 patients who had both SPECT 201Tl myocardial perfusion imaging and coronary angio/ventriculography for back projection reprocessing to accomplish the 360 degrees/180 degrees comparison. The results show a high incidence, 36% (9/25), of false-positive segmental perfusion abnormality and a high incidence, 24% (6/25), of moderate to severe degree of image distortion with the 180 degrees data sampled reconstructed images. These were not observed in the 360 degrees data sampled reconstructed images. The above findings confirmed our previous preliminary conclusion that even though the 180 degrees data sampling technique has the advantage of providing improved image contrast and reduction in acquisition time it is not a reliable technique and should be abandoned. The 360 degrees data sampling is the technique of choice for transaxial SPECT 201Tl myocardial perfusion imaging.

Symptomatic coronary artery disease in patients aged 21 to 30 years.

One hundred one young people (88 men, 13 women) aged 30 years or younger with arteriographically proved obstructive coronary artery disease (CAD) were identified and reviewed for risk factor prevalence. The men were compared with an age and date-of-catheterization matched control group who were arteriographically normal. Significant risk factors were cigarette smoking (p = 0.001), familial CAD (p = 0.002) and familial CAD manifested by age 50 years or younger (p = 0.005). Serum cholesterol values were significantly higher in the CAD group (p = 0.0001), but in most (54%) were still less than 250 mg/dl. Arteriography showed a spectrum of CAD: 1-vessel in 57, 2-vessel in 21 and 3-vessel in 22. One patient had significant left main CAD. Follow-up was obtained for all of the 94 American subjects. One-year mortality was 3% and 5-year mortality was 20%. The causes of death were predominantly cardiac: myocardial infarction in 10 patients, congestive heart failure in 2 and sudden death in 6; 3 patients died of noncardiac causes.