Splitting phonons: Building a platform for linear mechanical quantum computing.

Linear optical quantum computing provides a desirable approach to quantum computing, with only a short list of required computational elements. The similarity between photons and phonons points to the interesting potential for linear mechanical quantum computing using phonons in place of photons. Although single-phonon sources and detectors have been demonstrated, a phononic beam splitter element remains an outstanding requirement. Here we demonstrate such an element, using two superconducting qubits to fully characterize a beam splitter with single phonons. We further use the beam splitter to demonstrate two-phonon interference, a requirement for two-qubit gates in linear computing. This advances a new solid-state system for implementing linear quantum computing, further providing straightforward conversion between itinerant phonons and superconducting qubits.

The Effectiveness of Frailty Intervention for Older Patients with Frailty during Hospitalization.

OBJECTIVES: This study aims to assess the effectiveness of a multidomain intervention program on the change in functional status of hospitalized older adults. DESIGN: This single-arm, prospective, non-randomized interventional study investigates the efficacy of a multidomain interventional program including cognitive stimulation activity, simple exercises, frailty education, and nutrition counseling. SETTING AND PARTICIPANTS: At a tertiary hospital in southern Taiwan, 352 eligible patients were sequentially enrolled. Included patients were aged ≥65 years (mean age, 79.6 ± 9.0 years; 62% male), scored 3-7 on the Clinical Frailty Scale (CFS), and were hospitalized in the geriatric acute ward. INTERVENTION: Those receiving standard care (physical rehabilitation and nutrition counseling) during January-July 2019 composed the historical control group. Those receiving the multidomain intervention during August-December 2019 composed the intervention group. MEASUREMENTS: The primary outcome was the change in activities of daily life (ADL) and frailty status, as assessed by Katz Index and Clinical Frailty Scale, with using the generalized estimating equation model. The length of hospital stay, medical costs, and re-admission rates were secondary outcomes. RESULTS: Participants undergoing intervention (n = 101; 27.9%) showed greater improvements in the ADL and CFS during hospitalization (ADL adjusted estimate, 0.61; 95% CI, 0.11-1.11; p = 0.02; CFS adjusted estimate, -1.11; 95% CI, -1.42- -0.80; p < 0.01), shorter length of hospital stay (adjusted estimate, -5.00; 95% CI, -7.99- -2.47; p < 0.01), lower medical costs (adjusted estimate, 0.58; 95% CI, 0.49-0.69; p < 0.01), and lower 30- and 90-day readmission rates (30-day adjusted OR [aOR], 0.12; 95% CI, 0.27-0.50; p < 0.01; 60-day aOR, 0.04; 95% CI, 0.01-0.33; p < 0.01) than did controls. CONCLUSIONS: Participation in the multidomain intervention program during hospitalization improved the functional status and decreased the hospital stay length, medical costs, and readmission rates of frail older people.

Remote Entanglement via Adiabatic Passage Using a Tunably Dissipative Quantum Communication System.

Effective quantum communication between remote quantum nodes requires high fidelity quantum state transfer and remote entanglement generation. Recent experiments have demonstrated that microwave photons, as well as phonons, can be used to couple superconducting qubits, with a fidelity limited primarily by loss in the communication channel [P. Kurpiers et al., Nature (London) 558, 264 (2018)NATUAS0028-083610.1038/s41586-018-0195-y; C. J. Axline et al., Nat. Phys. 14, 705 (2018)NPAHAX1745-247310.1038/s41567-018-0115-y; P. Campagne-Ibarcq et al., Phys. Rev. Lett. 120, 200501 (2018)PRLTAO0031-900710.1103/PhysRevLett.120.200501; N. Leung et al., npj Quantum Inf. 5, 18 (2019)2056-638710.1038/s41534-019-0128-0; Y. P. Zhong et al., Nat. Phys. 15, 741 (2019)NPAHAX1745-247310.1038/s41567-019-0507-7; A. Bienfait et al., Science 364, 368 (2019)SCIEAS0036-807510.1126/science.aaw8415]. Adiabatic protocols can overcome channel loss by transferring quantum states without populating the lossy communication channel. Here, we present a unique superconducting quantum communication system, comprising two superconducting qubits connected by a 0.73 m-long communication channel. Significantly, we can introduce large tunable loss to the channel, allowing exploration of different entanglement protocols in the presence of dissipation. When set for minimum loss in the channel, we demonstrate an adiabatic quantum state transfer protocol that achieves 99% transfer efficiency as well as the deterministic generation of entangled Bell states with a fidelity of 96%, all without populating the intervening communication channel, and competitive with a qubit-resonant mode-qubit relay method. We also explore the performance of the adiabatic protocol in the presence of significant channel loss, and show that the adiabatic protocol protects against loss in the channel, achieving higher state transfer and entanglement fidelities than the relay method.

Phonon-mediated quantum state transfer and remote qubit entanglement.

Phonons, and in particular surface acoustic wave phonons, have been proposed as a means to coherently couple distant solid-state quantum systems. Individual phonons in a resonant structure can be controlled and detected by superconducting qubits, enabling the coherent generation and measurement of complex stationary phonon states. We report the deterministic emission and capture of itinerant surface acoustic wave phonons, enabling the quantum entanglement of two superconducting qubits. Using a 2-millimeter-long acoustic quantum communication channel, equivalent to a 500-nanosecond delay line, we demonstrate the emission and recapture of a phonon by one superconducting qubit, quantum state transfer between two superconducting qubits with a 67% efficiency, and, by partial transfer of a phonon, generation of an entangled Bell pair with a fidelity of 84%.

Urine specific gravity as a predictor of early neurological deterioration in acute ischemic stroke.

We previously found that a blood urea nitrogen/creatinine (BUN/Cr) ratio>15 is an independent predictor of early neurological deterioration after acute ischemic stroke, which suggests that dehydration may be a cause of early deterioration. The aim of this study was to determine whether urine specific gravity, which is another indicator of hydration status and one that is more easily obtained, is also an independent predictor of early deterioration or stroke-in-evolution (SIE). Demographic and clinical data were recorded at admission from patients with acute ischemic stroke who were prospectively enrolled from October 2007 to June 2010. We compared patients with and without stroke-in-evolution (based on an increase of 3 points or more points on the National Institutes of Health Stroke Scale within 3 days). Univariate and multivariate statistical analyses were carried out. A total of 317 patients (43 SIE and 274 non-SIE) were enrolled; the first 196 patients comprised the cohort of our previous study. The only two independent predictors of early deterioration or SIE were BUN/Cr>15 and urine specific gravity>1.010. After adjusting for age and gender, patients with a urine specific gravity>1.010 were 2.78 times more likely to develop SIE (95% CI=1.11-6.96; P=0.030). Urine specific gravity may be useful as an early predictor of early deterioration in patients with acute ischemic stroke. Patients with urine specific gravity ≤ 1.010 therefore may have a reduced likelihood of early neurological deterioration.

Haemoglobin in normal and neoplastic canine mammary glands.

Four types of globins for oxygen transport are known in vertebrates, and the haemoglobin is responsible for carrying oxygen in blood. In this study, we found that haemoglobin was also expressed in canine mammary glands. Samples were taken from 26 malignant mammary tumors, 16 normal mammary glands and 10 other normal tissues. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting and mass spectrometry were used to investigate haemoglobin in mammary tissues. The results indicated that normal canine mammary glands expressed high levels of haemoglobin protein as shown by Coomassie blue staining. The identity of haemoglobin was confirmed by immunoblotting and mass spectrometry, and the mass spectrometry data revealed that both alpha-haemoglobin and beta-haemoglobin were expressed. Relative to normal mammary glands, the levels of haemoglobin expression in mammary tumors were lower. Our results also indicated that the haemoglobin was endogenously produced in mammary gland tissues and was not derived from the erythroid cells.

Reversible cholestasis and cholangitis induced by biliary drainage and infusion in the rat.

To develop a rat model of ascending cholangitis, we constructed a controllable and accessible biliary drainage and infusion system. We first modified a reversible cholestasis model of the rat and then induced ascending cholangitis by administration of Escherichia coli into the proximal choledochostomy tube. After biliary infusion of E. coli, the liver, choledochostomy tube and bile were all positive for E. coli, but no bacteria grew in rats receiving biliary infusion of normal saline. Retrograde cholangiography of the initial choledochostomy ensured that the tube end was in the right position in the proximal common bile duct. The patency of the tube-tube choledochocholedochostomy was confirmed by a cholangiogram on day 90. Thirty days after the tube-tube choledochocholedochostomy, the livers of the experimental animals did not differ from the control livers. The tube-tube choledochocholedochostomy model not only provides reproducible, reliable, reversible cholestasis, but creates a sustainable and accessible biliary infusion system. This can be used for long-term investigations of repeated cholangitis and recurrent cholestasis.

A CD14 promoter polymorphism is associated with CD14 expression and Chlamydia-stimulated TNF alpha production.

CD14, a pattern recognition receptor on monocyte and macrophage, plays a central role in innate immunity through recognition of bacterial lipopolysaccharide and initiation of inflammatory response. Recently, CD14/-260C>T promoter gene polymorphism has been found to be related to a risk of inflammatory diseases. Our results showed that the C allele frequency among Chinese in Taiwan was lower than those in Western countries. The membrane CD14 expression was significantly higher in TT as compared with CT and CC genotypes (P=0.034, 0.044, respectively). There was a higher level of soluble CD14 in TT and CT genotypes than in CC genotypes. In addition, TNFalpha production in whole blood was significantly higher in TT genotype than in CC genotype after stimulation by Chlamydiae. In conclusion, the single base pair polymorphism of CD14 promoter gene is associated with CD14 expression and Chlamydia-stimulated TNFalpha production, and may thus play some role in the chlamydia-induced inflammatory response.

Determination and pharmacokinetic study of meropenem in rat bile using on-line microdialysis and liquid chromatography.

Meropenem is a carbapenem antibiotic with a wide spectrum of activity against both Gram-positive and Gram-negative bacteria. Because of its clinical efficacy, meropenem is an excellent choice for the treatment of serious infections in both adults and children. The knowledge of tissue concentrations of antibiotic in an infection site is valuable for the prediction of treatment outcome. To investigate the biliary disposition of meropenem, we utilized a minimally invasive sampling technique with a shunt linear microdialysis probe for continuous sampling in the biliary excretion studies. Analysis of meropenem in the dialysates was achieved using a LiChrosorb RP-18 column (Merck, 250 x 4.6 mm I.D.; particle size 5 microm) maintained at ambient temperature. The mobile phase was 50 mM monosodium phosphoric acid-methanol (80:20, v/v, pH 3.0). The UV detector wavelength was set at 298 nm. The area under the concentration-time curve and elimination half-lives of meropenem were about 6144 +/- 1494 min microg/ml and 61 +/- 17 min, respectively. This study represents a successful application of the microdialysis technique, which is an effective method for pharmacokinetic and biliary drug excretion studies.

Nonlinear multiwavelength conversion based on an aperiodic optical superlattice in lithium niobate.

We have demonstrated what is to our knowledge the first successful achievement of multiwavelength conversion in an aperiodic optical superlattice (AOS) lithium niobate crystal with equalized gain. The two AOS devices in our experiment, numerically synthesized from 2857 crystal blocks with a unit block thickness of 3.5 microm, have fundamental wavelengths of 1540 and 1545 nm for double-wavelength second-harmonic generation (SHG) and of 1540, 1545, and 1553 nm for triple-wavelength SHG at 50 degrees C. Our experiment and simulation show that the output spectrum of an AOS wavelength converter is fairly insensitive to typical fabrication errors.

Ascending cholangitis provokes IL-8 and MCP-1 expression and promotes inflammatory cell infiltration in the cholestatic rat liver.

BACKGROUND/PURPOSE: Postoperative cholangitis is one of the most common complications after bile duct reconstruction. The pathogenesis and early consequences of ascending cholangitis still are unidentified. METHODS: Male Sprague-Dawley rats were divided into 5 treatment groups: control (n = 4), blood sampling and liver biopsy only; group I, [BDL/Eschericha coli; n = 6], ligation of common bile duct (BDL) for a week, followed by Roux-en-Y choledochojejunostomy (RYCJ) and injection of E coli (ATCC 25922) into Roux limb after 24 hours; group II, [BDL/NS; n = 5], same procedures as in group I, with injection of normal saline (NS) into Roux limb; group III, [SBDL/E coli; n = 6], primary RYCJ was constructed 1 week after sham ligation of common bile duct (SBDL) followed by the same treatment as group I; Group IV, [SBDL/N.S; n = 6], same procedures as in group III, but injecting NS into Roux limb. All animals were killed after 24 hours of treatment. Blood was sampled for culture and serum cytokine levels. The liver was harvested for quantitative bacterial culture, as well as for MCP-1, interleukin (IL)-8 (CINC in the rat) and transforming growth factor beta1 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR) and for immunohistochemistry. The choledochojejunostomy was resected for culture. Serum cytokine levels were detected by ELISA kits. RESULTS: A significant increase of E coli ATCC 25922, occurred in the livers of group I rats, compared with group IV (P =.037). MCP-1 expression increased in all groups, compared with control (P =.000). The IL-8 mRNA expression was significantly higher in group I than in control (P =.021). The expression of TGF-beta1 mRNA was similar among the groups (P =.361), consistent with the immunohistochemistry results. The serum MCP-1 and IL-8 levels were higher in the 4 groups than in the control (P =.000) and were significantly higher in group I than in group IV (P =.001). CONCLUSIONS: This study found that a significant colonization of E coli of the same strain was present in the cholestatic rat liver injected into the Roux limb, which was associated with a higher expression of liver MCP-1 and IL-8 mRNA, a significant increase of serum MCP-1 and IL-8, and a more evident inflammatory cell infiltration into the porta hepatis.

Effects of Paeoniae Radix, a traditional Chinese medicine, on the pharmacokinetics of phenytoin.

BACKGROUND: Phenytoin (PHT), one of the most widely prescribed antiepileptic drugs, has been reported to be associated with numerous drug-drug interactions. However, there are far fewer reports about the pharmacokinetic interactions between PHT and traditional Chinese medicines (TCMs). Paeoniae Radix (PR), one of the well-known TCMs, is used as an adjunct in some epileptic patients. OBJECTIVE: In the present work, we studied the influences of PR on the pharmacokinetics of PHT in rats to identify the possible interactions between PR and PHT. METHOD: A single dose of PHT (100 mg/kg) alone or in combination with PR extract (300 mg/kg) was administered by gavage to male SD rats. Serial blood samples of PHT were obtained for up to 24 h post-administration and measured by high-performance liquid-chromatography. The free (unbound) plasma concentrations of PHT were determined by fluorescence polarization immunoassay. The plasma concentrations were used to construct pharmacokinetic profiles by plotting drug concentration-time curves. All data were subsequently processed by the computer program WINNONLIN. Statistical comparisons of pharmacokinetic parameters were performed with the unpaired Student t-test. RESULTS: The mean maximum plasma concentration of PHT was attained 2 h after oral administration of PHT alone and 4-6 h after oral administration of PHT in combination with PR. The plasma level of PHT declined with a half-life of 5.38 h after PHT alone and 4.03 h after PHT and PR given together. No statistically significant differences were obtained in most of the pharmacokinetic parameters (Cmax, AUC, t1/2, MRT and CL/F) and protein binding rates of PHT between the two treatments. However, significant differences in Tmax and Vd/F between groups were noted. CONCLUSION: The significant increase in Tmax indicated that simultaneous oral administration of PR delayed the absorption of PHT. The delayed absorption of PHT might lead to its slow onset of clinical effect. There were no significant differences in Cmax, AUC, t1/2, MRT and CL/F of PHT between the two groups, showing that PR could not significantly affect the extent of absorption, metabolism and elimination of PHT. No significant difference in protein binding rate was found, indicating that PR might not significantly alter the protein binding of PHT. While a significant decrease in Vd/F was noted, the mechanism underlying the apparently decreased Vd/F of PHT influenced by PR needs further study.

Effect of cyclosporine, a P-glycoprotein inhibitor, on the pharmacokinetics of cefepime in rat blood and brain: a microdialysis study.

In clinical application, cefepime and cyclosporine are regularly combined in the treatment of organ transplant patients, so the interaction of these two drugs can be hypothesized. Therefore, the pharmacokinetics of cefepime alone and in combination with cyclosporine in rat using microdialysis coupled with HPLC-UV on-line system was evaluated in the study. Cefepime at three doses (20, 50, and 100 mg/kg) showed linear kinetics. After addition of cyclosporine, the mean residence time was increased from 34.9 min to 48.6 min (p<0.05, n=6), and the area under the concentration versus time curve (AUC) increased from 4775 min microg/ml to 6960 min microg/ml (p<0.01, n=6). While in the brain, AUC increased from 64.3 min microg/ml to 110.2 min microg/ml. In summary, cyclosporine (20 mg/kg) could significantly alter the simultaneously administered cefepime (50 mg/kg) unbound drug pharmacokinetic parameters in both blood and brain.

Determination and pharmacokinetic study of unbound cefepime in rat bile by liquid chromatography with on-line microdialysis.

Biliary excretion and intestinal reabsorption in enterohepatic circulation play major dispositional roles for some drugs. To investigate biliary excretion of drug, we inserted a microdialysis probe into the bile common duct of rat between the liver and the duodenum. In order to avoid the obstruction of bile fluid or bile salt waste, a shunt linear microdialysis probe was used for simultaneous and continuous sampling following intravenous administration of cefepime (50 mg/kg, i.v.). Separation and quantitation of cefepime in the dialysates were achieved using a LiChrosorb RP-18 column (Merck; 250x4.6 mm I.D., particle size 5 microm) maintained at ambient temperature. Samples were eluted with a mobile phase containing 100 mM monosodium phosphoric acid (pH 3.0)-methanol (87:13, v/v). The UV detector wavelength was set at 270 nm. The result indicates that the elimination half-life of cefepime in bile was 64.01+/-9.32 min. This study also served as an example for the microdialysis application in the biliary excretion study of drug.

Lack of pharmacokinetic interaction between valproic acid and a traditional Chinese medicine, Paeoniae Radix, in healthy volunteers.

BACKGROUND AND OBJECTIVE: In addition to the standard antiepileptic drugs, traditional Chinese medicines (TCMs) are used for the treatment of epilepsy in oriental countries. The interactions between antiepileptic drugs and TCMs represent a potential problem in clinical application. Because valproic acid (VPA), one of the most widely prescribed antiepileptic drugs, may be administered concomitantly with Paeoniae Radix (PR), one of the famous TCMs, in some epileptic patients, the present study was conducted to evaluate the influences of PR on the pharmacokinetics of VPA. METHOD: The pharmacokinetics of VPA were investigated in a randomized, open-label, two-way crossover study. Six healthy volunteers received the following treatments in a crossover design: (i) 1.2 g extract powder of Paeoniae Radix once daily for 7 days and one 200 mg VPA gastro-resistant tablet on day 7 and (ii) one 200 mg VPA gastro-resistant tablet alone on day 7. Serial plasma samples were obtained on day 7. Total and free (unbound) VPA plasma concentrations were determined by fluorescence polarization immunoassay (FPIA). Safety measures included laboratory tests (haematology, serum chemistry and urinalysis) and adverse event monitoring. Statistical comparisons of pharmacokinetic parameters were performed with the Student paired t-test. RESULTS: Overall clinical safety was satisfactory. The mean maximum plasma concentration of VPA was attained at within 6 h after oral administration of VPA alone and 3-4 h after oral administration of VPA in combination with PR. The plasma level of VPA declined with a half-life of 11.71 and 11.91 h, respectively. No statistically significant difference was obtained in any of the pharmacokinetic parameters (Tmax, Cmax, AUC, t1/2, MRT, CL/F and Vd/F) of VPA between the two treatments. Also, there was no significant difference in the protein binding rates of VPA. CONCLUSION: PR did not significantly affect the absorption, distribution, metabolism and elimination of VPA in healthy volunteers.

Simultaneous determination of unbound cefoperazone in rat blood and brain using microdialysis.

A sensitive microbore HPLC method was developed for the simultaneous determination of unbound cefoperazone in rat blood and brain using microdialysis. Two microdialysis probes were inserted into the jugular vein/right atrium and brain striatum of Sprague-Dawley rats. Cefoperazone (50 mgkg(-1), i.v.) was then administered via the femoral vein. Blood and brain dialysates were collected and eluted with a mobile phase containing methanol-100 mM monosodium phosphoric acid (30:70, v/v, pH 5.5). The wavelength of the UV detector was set at 254 nm. The detection limit of cefoperazone was 20 ng mL(-1). Isocratic separation of cefoperazone was achieved within 10 min. The intra- and inter-assay accuracy and precision of the analyses were < or =10% in the range of 0.05-10 microg mL(-1). The ratio of the area under the concentration curve of cefoperazone in rat brain and blood was estimated to be about 7-8%. It is concluded that cefoperazone is capable of penetrating the blood-brain barrier.

Drug utilization pattern of antiepileptic drugs and traditional Chinese medicines in a general hospital in Taiwan - a pharmaco-epidemiologic study.

OBJECTIVE: Studies on antiepileptic drug utilization are important for the optimization of drug therapy and drug control. The present study was to evaluate the drug utilization pattern of standard antiepileptic drugs and traditional Chinese medicines (TCMs) in the treatment of different types of epilepsy in a general hospital in Taiwan. METHOD: The epileptic patients under antiepileptic drug treatment at Veterans General Hospital-Taipei were considered in the analysis. Current diagnosis was obtained by the neurologist in charge of the patient. All patients were interviewed by standard questionnaire designed to provide specific information on the types of antiepileptic drugs and details of their use. The questionnaire also sought to determine whether TCMs were used, and whether patients were using TCMs in combination with hospital standard treatment. The results were analysed by descriptive statistics. RESULTS: 729 patients with epilepsy definitely diagnosed were analysed in the study. 445 patients (61.04%) were prescribed with one antiepileptic drug. Combinations of two antiepileptic drugs were prescribed to 261 patients (35.80%), and combinations of three or more antiepileptic drugs to 23 patients (3.16%). A total of 1039 antiepileptic drugs was prescribed, corresponding to an average 1.42 drugs per patient. The most frequently prescribed antiepileptic drug was carbamazepine (56.93%), followed by phenytoin (31.96%), valproate (30.73%) and clonazepam (14.13%). Among the 729 epileptic patients, 83.68% used standard antiepileptic drugs alone, 16.32% used antiepileptic drugs in combination with TCMs. CONCLUSION: Monotherapy is the type of therapy most frequently used in all types of seizures. The selection of antiepileptic drugs is based on efficacy for specific seizure types and epileptic syndromes. The most frequently prescribed antiepileptic drug was carbamazepine, followed by phenytoin, valproate and clonazepam. As some of the patients used TCMs for treatment of epilepsy even when scientific medicine has been provided, further studies on the possible interactions between TCMs and antiepileptic drugs are in progress.

Renal allograft dysfunction associated with rifampin-tacrolimus interaction.

OBJECTIVE: To report an interaction between tacrolimus and rifampin with subsequent adverse effects on renal allograft function. CASE SUMMARY: A 61-year-old Chinese man received a cadaveric renal transplant in 1991. Progressive deterioration of allograft function developed during the following six years while the patient was receiving cyclosporine and prednisolone. In January 1998, tacrolimus was substituted for cyclosporine for late biopsy-proven graft rejection, with target trough blood concentrations between 5 and 8 ng/mL. After conversion, serum creatinine fell to 2.0 mg/dL; the nadir was reached within one year. At the same time, rifampin was instituted for controlling tuberculosis and empiric fluconazole was discontinued. Twelve days later, the patient's serum creatinine concentration rose to 2.9 mg/dL and tacrolimus concentration fell to 1.5 ng/mL, along with oliguria. These findings suggested acute rejection, which was successfully reversed by steroid therapy. However, more than a tenfold increase in the tacrolimus dosage was required to maintain the same concentrations during subsequent months, accompanied by an increase in serum creatinine (from 2.0 to 2.6 mg/dL) and decrease in urine excretion. Biopsy at this time demonstrated acute rejection (Banff I), chronic allograft nephropathy (Banff II), and suspected tacrolimus nephrotoxicity. After unsuccessful methylprednisolone recycling, mycophenolate mofetil was introduced to control rejection and facilitate reduction of the tacrolimus dosage to minimize its nephrotoxicity. CONCLUSIONS: As a potent CYP3A4 isoenzyme inducer, rifampin coadministration caused the abrupt decrease in tacroiimus blood concentrations, leading to an approximate tenfold increase in its daily dose, which may be important to subsequent allograft dysfunctions.