Phononic bath engineering of a superconducting qubit.

Phonons, the ubiquitous quanta of vibrational energy, play a vital role in the performance of quantum technologies. Conversely, unintended coupling to phonons degrades qubit performance and can lead to correlated errors in superconducting qubit systems. Regardless of whether phonons play an enabling or deleterious role, they do not typically admit control over their spectral properties, nor the possibility of engineering their dissipation to be used as a resource. Here we show that coupling a superconducting qubit to a bath of piezoelectric surface acoustic wave phonons enables a novel platform for investigating open quantum systems. By shaping the loss spectrum of the qubit via the bath of lossy surface phonons, we demonstrate preparation and dynamical stabilization of superposition states through the combined effects of drive and dissipation. These experiments highlight the versatility of engineered phononic dissipation and advance the understanding of mechanical losses in superconducting qubit systems.

Piezoacoustics for precision control of electrons floating on helium.

Piezoelectric surface acoustic waves (SAWs) are powerful for investigating and controlling elementary and collective excitations in condensed matter. In semiconductor two-dimensional electron systems SAWs have been used to reveal the spatial and temporal structure of electronic states, produce quantized charge pumping, and transfer quantum information. In contrast to semiconductors, electrons trapped above the surface of superfluid helium form an ultra-high mobility, two-dimensional electron system home to strongly-interacting Coulomb liquid and solid states, which exhibit non-trivial spatial structure and temporal dynamics prime for SAW-based experiments. Here we report on the coupling of electrons on helium to an evanescent piezoelectric SAW. We demonstrate precision acoustoelectric transport of as little as ~0.01% of the electrons, opening the door to future quantized charge pumping experiments. We also show SAWs are a route to investigating the high-frequency dynamical response, and relaxational processes, of collective excitations of the electronic liquid and solid phases of electrons on helium.

Structure-activity relationships of trans-substituted-propenoic acid derivatives on the nicotinic acid receptor HCA2 (GPR109A).

Nicotinic acid (niacin) has been used for decades as an antidyslipidemic drug in man. Its main target is the hydroxy-carboxylic acid receptor HCA2 (GPR109A), a G protein-coupled receptor. Other acids and esters such as methyl fumarate also interact with the receptor, which constituted the basis for the current study. We synthesized a novel series of substituted propenoic acids, such as fumaric acid esters, fumaric acid amides and cinnamic acid derivatives, and determined their affinities for the HCA2 receptor. We observed a rather restricted binding pocket on the receptor with trans-cinnamic acid being the largest planar ligand in our series with appreciable affinity for the receptor. Molecular modeling and analysis of the structure-activity relationships in the series suggest a planar trans-propenoic acid pharmacophore with a maximum length of 8 Å and out-of-plane orientation of the larger substituents.

Population pharmacokinetics of vancomycin in adult and geriatric patients: comparison of eleven approaches.

PURPOSE: A vancomycin population pharmacokinetic prediction model for adult and elderly patients was developed using NONMEM. The predictability of the model was studied and compared with ten other models. METHODS: Data were collected from routine care of 141 subjects. NONMEM was used to derive a population model. After internal evaluation using the bootstrap technique, external validation was studied using an independent dataset that consisted of 95 subjects; a statistical comparison of precision and bias was conducted. RESULTS: A two-compartment open model was derived with body weight, age, and CLcr as covariates. The bootstrap process showed stability of the model. A comparison of subjects older and younger than 65 years found that the older group had a mean clearance of 2.24 (+/- 1.2) l/h compared to 4.03 (+/- 1.7) l/h, and a peripheral volume of 43.7 (+/- 5.1) l compared to 28.4 (+/- 5.3) l compared to younger patients. These values were modeled using CLcr in the clearance equation and Vd as a function of age. The eleven models studied showed a bias in predicting serum concentrations from the test database that ranged from 0.35 mg/l to -5.93 mg/l. Precision ranged from 4.53 mg/l to 8.05 mg/l. Our method ranked in fourth place overall and when compared statistically its bias was different from the method that ranked in second place by -1.45 (95% CI -2.46, -0.42; p = 0.005), and different from all the methods that ranked worse. The only difference in precision was with the method that ranked in eleventh place with a relative precision of 0.49 (95% CI 0.27, 0.70; p < 0.001). CONCLUSIONS: A two-compartment open model fitted the data with weight, age, and CLcr as covariates. The derived method ranked in fourth place overall. The two-compartment nature of two of the equations studied did not provide an advantage. A future study with more data in the distribution phase could provide a model with better predictability.

Ability of new APTIMA CT and APTIMA GC assays to detect Chlamydia trachomatis and Neisseria gonorrhoeae in male urine and urethral swabs.

A clinical evaluation was conducted in six North American centers to determine the ability of APTIMA CT (ACT) and APTIMA GC (AGC) nucleic acid amplification assays to detect Chlamydia trachomatis and Neisseria gonorrhoeae infections in 1,322 men by testing their urethral swabs and first-catch urine (FCU). The results obtained with ACT and AGC assays were compared to an infected patient status determined by testing the specimens with the APTIMA Combo 2 and the BD ProbeTec energy transfer multiplex assays. Symptoms did not influence the values. Positive and negative agreements of the ACT and AGC assays for individual specimens were high, with each comparator assay ranging between 94.3 and 100% for positives and 93.9 and 99.4% for negatives. The ACT and AGC assays performed on noninvasive specimens such as FCU effectively identified C. trachomatis or N. gonorrhoeae infections in symptomatic and asymptomatic men and should be suitable for screening male populations.

Improved recovery of active recombinant laccase from maize seed.

Lignolytic enzymes such as laccase have been difficult to over-express in an active form. This paper describes the expression, characterization, and application of a fungal laccase in maize seed. The transgenic seed contains immobilized and extractable laccase. Fifty ppm dry weight of aqueously extractable laccase was obtained, and the remaining solids contained a significant amount of immobilized laccase that was active. Although a portion of the extractable laccase was produced as inactive apoenzyme, laccase activity was recovered by treatment with copper and chloride. In addition to allowing the apoenzyme to regain activity, treatment with copper also provided a partial purification step by precipitating other endogenous corn proteins while leaving >90% of the laccase in solution. The data also demonstrate the application of maize-produced laccase as a polymerization agent. The apparent concentration of laccase in ground, defatted corn germ is approximately 0.20% of dry weight.

The influences of renal function and maturation on vancomycin elimination in newborns and infants.

The purpose of this study was to describe the maturation of vancomycin (V) clearance and the influence of altered renal function in infants on vancomycin using population pharmacokinetic methods. A population pharmacokinetic model was developed using NONMEM from clinical data obtained from 374 newborns and infants < 2 years of age (median age = 27 days) from four institutions. A total of 1103 serum V concentrations were used in the model development, including 311 with elevated serum creatinine (CR) (> 0.8 mg/dl) and more than 104 evaluations in infants older than 2 months of age. The final model was evaluated against a second data set of 160 concentrations from 67 infants at one of the institutions and then used to develop dosing guidelines. The data were best described by a two-compartment model. Weight and CR greatly influenced vancomycin elimination, while postnatal age and prematurity (< 28 weeks) were significant but less important predictors of V elimination. For the typical study infant (age = 27 days, CR = 0.6, WT= 1.8 kg, gestational age = 33.5 weeks), this results in VdSS = 0.79 l/kg and Cl = 0.066 l/h/kg. The validation data set showed the model to be unbiased. Dosing guidelines from this model, based on serum creatinine and gestational age at birth, performed better than published guidelines based on postconceptional age. Vancomycin clearance is initially reduced in premature infants and increases with postnatal age. Most of the age-related changes could be predicted by the concomitant fall in serum creatinine. Dosing guidelines that incorporate these factors are more likely to produce therapeutic V concentrations in infants.

In utero diagnosis of obstructed supracardiac total anomalous pulmonary venous connection in a patient with right atrial isomerism and asplenia.

We describe a rare case of right atrial isomerism, levocardia, right-side stomach, obstructed supracardiac total anomalous pulmonary venous connection, double outlet right ventricle with complete atrioventricular septal defect and absent spleen. From the pulmonary venous confluence behind the atrium an ascending as well as a descending vertical vein communicated with the systemic venous system in the supracardiac as well as the infracardiac position. The pulsed and color Doppler examination of the individual pulmonary veins as well as of the vertical vein helped in making the diagnosis of obstructed total anomalous pulmonary venous connection. The diagnosis was made by fetal echocardiographic examination at 22 weeks of gestation and confirmed on postnatal echocardiography, cardiac catheterization, and at surgery.

Dichloroacetate: population pharmacokinetics with a pharmacodynamic sequential link model.

Dichloroacetate (DCA) is a small molecule that reduces ambient concentrations of lactate in man. It was the purpose of this study to develop pharmacokinetic and pharmacodynamic models for determination of a dose for a pivotal Phase III clinical trial of DCA in patients with traumatic brain injury (TBI). Population pharmacokinetic and pharmacodynamic models were developed for DCA using NONMEM software. The pharmacokinetic data were fit to a physiologic two-compartment model, and the pharmacodynamic data were fit to an indirect physiologic response model. Simulations were employed to evaluate various dosing strategies for consideration in a pivotal Phase III clinical trial of DCA. For the pharmacokinetic model, it was discovered that the clearance of DCA decreased on multiple dosing from 4.82 L/h to 1.07 L/h and that the pharmacokinetics and pharmacodynamics in TBI patients could not be predicted from normal volunteers. Population pharmacokinetic modeling and simulation of the expected effects of several dosing strategies were useful procedures for designing a Phase III trial.

Successful short-segment instrumentation and fusion for thoracolumbar spine fractures: a consecutive 41/2-year series.

STUDY DESIGN: A retrospective review of all the surgically managed spinal fractures at the University of Missouri Medical Center during the 41/2-year period from January 1989 to July 1993 was performed. Of the 51 surgically managed patients, 46 were instrumented by short-segment technique (attachment of one level above the fracture to one level below the fracture). The other 5 patients in this consecutive series had multiple trauma. These patients were included in the review because this was a consecutive series. However, they were grouped separately because they were instrumented by long-segment technique because of their multiple organ system injuries. OBJECTIVES: The choice of the anterior or posterior approach for short-segment instrumentation was based on the Load-Sharing Classification published in a 1994 issue of Spine. The purpose of this review was to demonstrate that grading comminution by use of the Load-Sharing Classification for approach selection and the choice of patients with isolated fractures who are cooperative with spinal bracing for 4 months provide the keys to successful short-segment treatment of isolated spinal fractures. SUMMARY OF BACKGROUND DATA: The current literature implies that the use of pedicle screws for short-segment instrumentation of spinal fracture is dangerous and inappropriate because of the high screw fracture rate. METHODS: Charts, operative notes, preoperative and postoperative radiographs, computed tomography scans, and follow-up records of all patients were reviewed carefully from the time of surgery until final follow-up assessment. The Load-Sharing Classification had been used prospectively for all patients before their surgery to determine the approach for short-segment instrumentation. Denis' Pain Scale and Work Scales were obtained during follow-up evaluation for all patients. RESULTS: All patients were observed over 40 months except for 1 patient who died of unrelated causes after 35 months. The mean follow-up period was 66 months (51/2 years). No patient was lost to follow-up evaluation. Prospective application of the Load-Sharing Classification to the patients' injury and restriction of the short-segment approach to cooperative patients with isolated spinal fractures (excluding multisystem trauma patients) allowed 45 of 46 patients instrumented by the short-segment technique to proceed to successful healing in virtual anatomic alignment. CONCLUSIONS: The Load-Sharing Classification is a straightforward way to describe the amount of bony comminution in a spinal fracture. When applied to patients with isolated spine fractures who are cooperative with 3 to 4 months of spinal bracing, it can help the surgeon select short-segment pedicle-screw-based fixation using the posterior approach for less comminuted injuries and the anterior approach for those more comminuted. The choice of which fracture-dislocations should be strut grafted anteriorly and which need only posterior short-segment pedicle-screw-based instrumentation also can be made using the Load-Sharing Classification.

Prospective diagnosis of alveolar capillary dysplasia in infants with congenital heart disease.

Alveolar capillary dysplasia (ACD) is a lethal pulmonary disorder found in newborns that is characterized by severe pulmonary hypertension and hypoxemia. We report on the clinical behavior of this disorder in a series of patients and its association with congenital heart disease, especially left heart obstructive disease; we also report a prospective diagnosis of ACD by lung biopsy in a newborn with congenital heart disease, which prevented futile and prolonged medical intervention.

Effects of bile duct ligation and captopril on salt appetite and renin-aldosterone axis in rats.

A ligation of the common bile duct (BDL) produces cholestasis and hypotension and increases the daily ingestion of sodium chloride solutions in rats. Low-dose captopril (CAP) treatment also modifies the ingestion of water and sodium in naive rats, and may do so in cholestatic rats. This study examined whether the elevated ingestion of saline by Long-Evans rats after BDL is associated with increased plasma renin activity (PRA), and whether treatment with a low dose of the angiotensin converting-enzyme inhibitor CAP further exacerbates fluid intake and PRA after BDL. In these experiments water and 0.3 M saline intake and PRA and plasma aldosterone (PA) were measured in naive and CAP-treated BDL and sham-ligated rats. We found that BDL elevated rats' daily saline intake 2 weeks after the ligation procedure but had no effect on PRA. CAP (0.1 mg/mL) placed in the drinking water of some BDL rats further increased saline intake. Both PA and hematocrits tended to be reduced in BDL rats, whereas PRA was elevated in both BDL and sham-ligated rats receiving CAP in the drinking water or by gavage (0.1 mg/mL in 10 mL/kg). The data suggest that the ingestion of saline by rats can be modified by BDL and CAP administration, but that exaggerated saline intake in BDL rats is not associated with excessive renin secretion.

Sodium ion uptake into isolated plasma membrane vesicles: indirect effects of other ions.

Vesicles derived from plasma membrane of corneal endothelium were agitated to their minimum size distribution. When isotonic salt solutions surrounding the vesicles were changed there were alterations to the vesicle size distribution: the modal point of the logarithmic distribution did not change but the log variance did, indicating that substantial fission and fusion of vesicles occurred depending upon the nature of the surrounding solute. Orientation and total membrane area was conserved in the transformed population of vesicles. Although the ions added to the external isotonic salt solutions in the present series of experiments have no direct effect upon sodium membrane transporters in these membranes, kinetics of sodium accumulation into the vesicles were affected in a way that correlated with changes to the vesicle size distribution. Early-saturating (<1 min) intravesicular concentrations of sodium corresponded with apparently stable populations. Late-saturating (>1 min) intravesicular concentrations of sodium corresponded with significant vesicle distribution shifts and included a few seconds of delay. During the linear accumulation phase, both populations showed similar magnitudes of sodium transport. The significance of these data is discussed.

Drinking and blood pressure during sodium depletion or ANG II infusion in chronic cholestatic rats.

After a chronic ligation of the common bile duct (BDL), Long-Evans rats are hypotensive and have elevated saline intake during both sodium-depleted and nondepleted conditions. We tested whether BDL rats have exaggerated hypotension during sodium depletion or an elevated dipsogenic response to angiotensin II (ANG II) that might help to explain the saline intake. After 4 wk of BDL, rats were hypotensive at baseline and developed exaggerated hypotension during acute furosemide-induced diuresis. Without saline to drink, BDL rats increased water intake during depletion equal to sham-ligated rats. However, with saline solution available at 22 h after sodium depletion, the BDL rats drank more water and saline than did sham-ligated rats. This rapid intake temporarily increased their mean arterial pressure to equal that of sham-ligated rats. Intravenous infusion of ANG II induced equal drinking responses despite reduced pressor responses in the BDL rats relative to sham-ligated rats during both ad libitum and sodium-depleted conditions. Thus BDL rats have exaggerated hypotension during diuresis, and their hypotension is corrected by drinking an exaggerated volume of saline, but they do not have an increased drinking response to ANG II.

Isolation and Expansion of HIV from Cells and Body Fluids by Coculture.

HIV can be recovered from infected patients at all stages of the disease spectrum. Typically, the quantity of biologically active virus, or viral protein, in body tissues is below the level of direct detection by either antigen capture or reverse transcriptase assays. Consequently, the virus must be expanded in culture. This may be achieved by the cocultivation of patient material with mitogen-stimulated peripheral blood mononuclear cells (PBMCs) from normal, healthy donors. These cocultures are then maintained by regularly scheduled interleukin-2 (IL-2) supplemented medium replacement, and the periodic addition of freshly stimulated normal donor PBMCs. During this cocultivation period, culture fluids are harvested at regular intervals and tested for the presence and subsequent replication of HIV. Cultures failing to demonstrate evidence of virus expression within 35 d are usually terminated.

Quantitative HIV Culture.

This procedure is used for establishing cocultures for virus isolation by an endpoint dilution assay in a 96-well tissue culture plate. This is a cell culture assay based on the detection of HIV in patient peripheral blood mononuclear cells (PBMC) by the appearance of p24 gag protein in the culture supernatant. It can be used in a research setting as a measure of viral burden because the number of patient cells required to produce a positive culture is indicative of cellular viral load.

Quantitation of Cell-Free HIV by Reverse Transcriptase Activity.

This assay measures the activity of reverse transcriptase (RNA-dependent-DNA polymerase), an enzyme that synthesizes DNA using RNA as the template. The detection of reverse transcriptase activity (RT) indicates the presence of HIV-1 in in vitro cultures of human peripheral blood mononuclear cells (PBMCs). Because active HIV-1 infection results in lysis of lymphocytes and release of free virions, the associated enzyme activity can be found in cell culture supernatants. Virus is concentrated from the supernatant and separated from soluble cellular contaminants by pelleting in polyethylene glycol and resuspended in a minimal volume of suspension buffer prior to assay.

Induced preference or conditioned aversion for sodium chloride in rats with chronic bile duct ligation.

We examined whether a learned aversion to saline could account for the reduction in saline intake produced by bile duct ligation (BDL) in rats and whether increased saline intake by BDL rats was associated with hypotension. In three experiments, rats were given continuous access to water in choice with saline after surgery. In Experiment 1, rats were deprived of food and fluid for 24 h and then given 2-h access to either 0.15 or 0.3 M saline. Rats received a BDL or sham-ligation immediately (paired) or 48 h after (nonpaired) the 2-h bout of saline ingestion. The results show that nonpaired BDL rats increased their daily saline intake relative to nonpaired sham-ligated or paired BDL rats approximately 1-4 weeks after surgery. In Experiment 2, when water and either cherry or grape Kool-Aid (0.05% w/v) dissolved in 0.15 M saline to distinguish the flavor of the solution was offered prior to surgery, BDL rats reduced their ingestion of grape-flavored saline after surgery regardless of whether they were exposed to grape- or cherry-flavored saline prior to surgery. In Experiment 3, when rats were offered water and 0.3 M saline 48 h after surgery, BDL rats ligated for 4 weeks increased their saline intake relative to sham-ligated controls and this elevation in saline intake by BDL rats was associated with hypotension. The results suggest that the symptoms associated with the BDL surgery can serve as effective unconditioned stimuli in the acquisition of learned flavor aversions, and that hypotension may play a role in the elevated intake of saline by BDL rats.

Transport of deuterium-labeled tocopherols during pregnancy.

With use of deuterium-labeled isotopes of RRR- and all-rac-alpha-tocopheryl acetate, the transport of vitamin E in pregnancy was evaluated to determine whether the placenta discriminates between these compounds. Fifteen pregnant subjects were recruited 5 d before delivery to receive 15, 30, 75, 150, or 300 mg vitamin E/d in capsules containing d3-RRR-alpha-tocopheryl acetate and d6-all-rac-alpha-tocopheryl acetate (1:1, by wt). Maternal blood was obtained before dosing, at hospital admission, and at parturition. Cord blood samples were obtained at parturition. Deuterium-labeled and unlabeled tocopherol contents were determined by gas chromatography-mass spectrometry in plasma and lipoproteins (chylomicrons, VLDL, LDL, and HDL). Maternal plasma and lipoproteins obtained at delivery had higher concentrations of d3-RRR-alpha-tocopherol than d6-all-rac-alpha-tocopherol regardless of the vitamin E dose administered (P < 0.05). Cord plasma at delivery also had higher concentrations of d3-RRR-alpha-tocopherol than d6-all-rac-alpha-tocopherol in plasma irrespective of the dose administered (P < 0.05). In lipoproteins isolated from cord blood, tocopherol concentrations were greatest in the HDL fraction (P < 0.05), whereas in maternal blood they were greatest in the LDL fraction (P < 0.05). We conclude that the placental-fetal unit, the fetal liver, or both further discriminate between RRR- and all-rac-alpha-tocopherol.

Protein phosphatase inhibitors calyculin A and fostriecin protect rabbit cardiomyocytes in late ischemia.

Calcium-tolerant rabbit cardiomyocytes were isolated using retrograde aortic perfusion with a nominally calcium-free, collagenase buffer. In vitro ischemic preconditioning was induced by a 10-min episode of ischemic pelleting, followed by a 15-min post-incubation and a prolonged period of ischemic pelleting. Injury was assessed by determination of cell contracture and trypan blue permeability following hypotonic swelling and correlated with metabolic assays of lactate and adenine nucleotides. The protein phosphatase PP1/2A inhibitor calyculin A and PP2A-selective fostriecin protected isolated rabbit cardiomyocytes from lethal injury after a 10-min pre-incubation and when added late into ischemic pellets after a delay of 75 min. At the time of late drug addition, cells were severely ATP-depleted and in rigor contracture. Protection with Calyculin A from 1 nM to 1 microM was dose-related. Cells pre-incubated with 10 nM to 10 microM fostriecin 10 min prior to ischemic pelleting were protected with an EC50 approximating 71 nM, implying protection at a PP2A-selective dose. The selective protein kinase C inhibitor, calphostin C, blocked ischemic preconditioning protection but not protection from 1 microM calyculin A. Protection of severely ischemic cardiomyocytes following protein phosphatase inhibition appears not to require PKC activity or ATP conservation. Pre-incubation of cells with calyculin A induced high levels of phosphorylation in p38 mitogen activated protein kinase (MAPK), as compared to the ischemia-induced phosphorylation observed in the untreated group only at 30 min of ischemia, providing evidence of protein phosphatase activity in cardiomyocytes. Pharmacological protection in late ischemia has been demonstrated, but the mechanism of protection is undetermined.