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Abstract Scalable quantum processors require high-fidelity universal quantum logic operations in a manufacturable physical platform. Donors in silicon provide atomic size, excellent quantum coherence and compatibility with standard semiconductor processing, but no entanglement between donor-bound electron spins has been demonstrated to date. Here we present the experimental demonstration and tomography of universal one- and two-qubit gates in a system of two weakly exchange-coupled electrons, bound to single phosphorus donors introduced in silicon by ion implantation. We observe that the exchange interaction has no effect on the qubit coherence. We quantify the fidelity of the quantum operations using gate set tomography (GST), and we use the universal gate set to create entangled Bell states of the electrons spins, with fidelity 91.3 ± 3.0%, and concurrence 0.87 ± 0.05. These results form the necessary basis for scaling up donor-based quantum computers.

Abstract Semiconductor spin qubits represent a promising platform for future large-scale quantum computers owing to their excellent qubit performance, as well as the ability to leverage the mature semiconductor manufacturing industry for scaling up. Individual qubit control, however, commonly relies on spectral selectivity, where individual microwave signals of distinct frequencies are used to address each qubit. As quantum processors scale up, this approach will suffer from frequency crowding, control signal interference and unfeasible bandwidth requirements. Here, we propose a strategy based on arrays of degenerate spins coherently dressed by a global control field and individually addressed by local electrodes. We demonstrate simultaneous on-resonance driving of two degenerate qubits using a global field while retaining addressability for qubits with equal Larmor frequencies. Furthermore, we implement SWAP oscillations during on-resonance driving, constituting the demonstration of driven two-qubit gates. Significantly, our findings highlight how dressing can overcome the fragility of entangling gates between superposition states and increase their noise robustness. These results constitute a paradigm shift in qubit control in order to overcome frequency crowding in large-scale quantum computing.

Abstract Spins of electrons in silicon MOS quantum dots combine exquisite quantum properties and scalable fabrication. In the age of quantum technology, however, the metrics that crowned Si/SiO2 as the microelectronics standard need to be reassessed with respect to their impact upon qubit performance. We chart spin qubit variability due to the unavoidable atomic-scale roughness of the Si/SiO2 interface, compiling experiments across 12 devices, and develop theoretical tools to analyse these results. Atomistic tight binding and path integral Monte Carlo methods are adapted to describe fluctuations in devices with millions of atoms by directly analysing their wavefunctions and electron paths instead of their energy spectra. We correlate the effect of roughness with the variability in qubit position, deformation, valley splitting, valley phase, spin-orbit coupling and exchange coupling. These variabilities are found to be bounded, and they lie within the tolerances for scalable architectures for quantum computing as long as robust control methods are incorporated.

Quantum computing, communications, sensing, and simulations are radically transformative technologies, with great potential to impact industries and economies. Worldwide, national governments, industries, and universities are moving to create a new class of workforce—the Quantum Engineers. Demand for such engineers is predicted to be in the tens of thousands within a five-year timescale, far exceeding the rate at which the world’s universities can produce Ph.D. graduates in the discipline. How best to train this next generation of engineers is currently a matter of debate. Quantum mechanics—long a pillar of traditional physics undergraduate degrees—must now be merged with traditional engineering offerings. This article discusses the history, development, and the first year of operation of the world’s first undergraduate degree in quantum engineering to be grown out of an engineering curriculum. The main purpose of this article is to inform the wider discussion, now being held by many institutions worldwide, on how best to formally educate the Quantum Engineer.

Multielectron quantum dots offer a promising platform for high-performance spin qubits; however, previous demonstrations have been limited to single-qubit operation. Here, the authors report a universal gate set and two-qubit Bell state tomography in a high-occupancy double quantum dot in silicon.

Quantum computation relies on accurate measurements of qubits not only for reading the output of the calculation, but also to perform error correction. Most proposed scalable silicon architectures utilize Pauli blockade of triplet states for spin-to-charge conversion. In recent experiments there have been instances when instead of conventional triplet blockade readout, Pauli blockade is sustained only between parallel spin configurations, with |T_{0}⟩ relaxing quickly to the singlet state and leaving |T_{+}⟩ and |T_{−}⟩ states blockaded—which we call parity readout. Both types of blockade can be used for readout in quantum computing, but it is crucial to maximize the fidelity and understand in which regime the system operates. We devise and perform an experiment in which the crossover between parity and singlet-triplet readout can be identified by investigating the underlying physics of the |T_{0}⟩ relaxation rate. This rate is tunable over 4 orders of magnitude by controlling the Zeeman energy difference between the dots induced by spin-orbit coupling, which in turn depends on the direction of the applied magnetic field. We suggest a theoretical model incorporating charge noise and relaxation effects that explains quantitatively our results. Investigating the model both analytically and numerically, we identify strategies to obtain on demand either singlet-triplet or parity readout consistently across large arrays of dots. We also discuss how parity readout can be used to perform full two-qubit state tomography and its impact on quantum error-detection schemes in large-scale silicon quantum computers.

Silicon quantum dots are considered an excellent platform for spin qubits, partly due to their weak spin-orbit interaction. However, the sharp interfaces in the heterostructures induce a small but significant spin-orbit interaction that degrades the performance of the qubits or, when understood and controlled, could be used as a powerful resource. To understand how to control this interaction, we build a detailed profile of the spin-orbit interaction of a silicon metal-oxide-semiconductor double quantum-dot system. We probe the derivative of the Stark shift, g-factor and g-factor difference for two single-electron quantum-dot qubits as a function of external magnetic field and find that they are dominated by spin-orbit interactions originating from the vector potential, consistent with recent theoretical predictions. Conversely, by populating the double dot with two electrons, we probe the mixing of singlet and spin-polarized triplet states during electron tunneling, which we conclude is dominated by momentum-term spin-orbit interactions that vary from 1.85 MHz up to 27.5 MHz depending on the magnetic field orientation. Finally, we exploit the tunability of the derivative of the Stark shift of one of the dots to reduce its sensitivity to electric noise and observe an 80% increase in T_{2}^{*}. We conclude that the tuning of the spin-orbit interaction will be crucial for scalable quantum computing in silicon and that the optimal setting will depend on the exact mode of qubit operations used.

Antibody-drug conjugates (ADCs) require thorough characterization and understanding of product quality attributes. The framework of many ADCs comprises one molecule of antibody that is usually conjugated with multiple drug molecules at various locations. It is unknown whether the drug release rate from the ADC is dependent on drug location, and/or local environment, dictated by the sequence and structure of the antibody carrier. This study addresses these issues with valine-citrulline-monomethylauristatin E (vc-MMAE)-based ADC molecules conjugated at reduced disulfide bonds, by evaluating the cathepsin B catalyzed drug release rate of ADC molecules with different drug distributions or antibody carriers. MMAE drug release rates at different locations on ADC I were compared to evaluate the impact of drug location. No difference in rates was observed for drug released from the V(H), V(L), or C(H)2 domains of ADC I. Furthermore, four vc-MMAE ADC molecules were chosen as substrates for cathepsin B for evaluation of Michaelis-Menten parameters. There was no significant difference in K(M) or k(cat) values, suggesting that different sequences of the antibody carrier do not result in different drug release rates. Comparison between ADCs and small molecules containing vc-MMAE moieties as substrates for cathepsin B suggests that the presence of IgG1 antibody carrier, regardless of its bulkiness, does not impact drug release rate. Finally, a molecular dynamics simulation on ADC II revealed that the val-cit moiety at each of the eight possible conjugation sites was, on average, solvent accessible over 50% of its maximum solvent accessible surface area (SASA) during a 500 ns trajectory. Combined, these results suggest that the cathepsin cleavage sites for conjugated drugs are exposed enough for the enzyme to access and that the drug release rate is rather independent of drug location or monoclonal antibody carrier. Therefore, the distribution of drug conjugation at different sites is not a critical parameter to control in manufacturing of the vc-MMAE-based ADC conjugated at reduced disulfide bonds.

Conjugation of an antibody to a drug can produce heterogeneous species that may have different physical stabilities and safety profiles. We explored the effect of thermal stress on the physical stability, specifically aggregation, of an antibody drug conjugate (ADC), ADC 1, wherein the antibody was linked to the val-cit-Monomethyl Auristatin E (vc-MMAE) linker drug through the reduction of interchain disulfides. We also explored the effects of conjugation on the secondary and tertiary structures of ADC 1. Circular dichroism, intrinsic tryptophan fluorescence, and differential scanning calorimetry showed that for species with high drug loading, conjugation does not measurably alter the secondary structure, but it does render the CH2 domain less stable to thermal stress such that ADC 1 rapidly forms high molecular weight species (HMWS) at 40 °C. Characterization of the HMWS using chromatographic and electrophoretic methods showed that it is an irreversible, noncovalent, and structurally altered form of ADC 1 primarily composed of molecules with six or eight drugs. Furthermore, the variable domain of the antibody may contribute to the extent of aggregation, since eight ADCs with over 90% sequence homology exhibited monthly rates of HMWS formation that differ by up to a factor of 2.

Isomerization of aspartyl (Asp or D) residues is a critical degradation route to consider for stable monoclonal antibody formulations. Among the known hotspot sequences, the DD motif is relatively understudied. To gain mechanistic insights, we used model hexapeptides, YADXFK, YADDXK, and DIDDDM, as surrogates for the hotspots in a Fab protein (YADDFK and DIDDDM), to characterize the rate-pH profile of Asp isomerization. Compared with the YADGFK peptide, isomerization of D3 (the first D in the DD pair) in YADDFK was highly pH dependent. Comparison of rate-pH profiles of YADDFK, YADNFK, and YADHFK revealed a charge effect of the n + 1 residue-isomerization rate is accelerated by the positive side chain and reduced by negative side chain at n + 1 residue. Studies on YADDFK, YADDAK, and YADDGK indicated a mutual impact of D3 and D4 on their respective isomerization rates through charge effect. Comparison of rate-pH profile of DIDDDM sequence in peptide models with that in the complementary determining region of the Fab showed a faster rate in the Fab than in peptides, presumably because of contribution from structural factors in the former., (Copyright © 2012 Wiley Periodicals, Inc.)

Unexpected release of free drug was observed during the stability testing of an antibody-drug conjugate (ADC). The ADC was designed to use lysine-succinimidyl ester chemistry to conjugate small molecule cytotoxic drugs to the antibody. To elucidate the mechanism of the release of free drug, a succinimidyl ester analog, 7-hydroxy-4-methyl-3-coumarinylacetic acid N-succinimidyl ester, and a series of peptides were used to probe the potential side reaction of succinimidyl ester with other amino acid residues. Cysteine and tyrosine residues were found to be reactive to succinimidyl ester, and the bonds formed through these reactions were found to be labile. Combining the fluorescent property of the succinimidyl ester analog and mass spectroscopy analysis, specific cysteine and tyrosine residues of the antibody were found to be reactive to succinimidyl ester and the bonds formed through this reaction were susceptible to hydrolysis., (Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association)

We develop a heterodyne polariscope for measuring the two-dimensional principal axis and phase retardation in a linear birefringence material using novel three-frame and two-frame integrating-bucket methods and a CCD. By using a complex programmable logic device to provide an external trigger to the CCD, integrating buckets with multiple frames are achieved. The advantages of the proposed three-frame and two-frame integrating-bucket methods include a simpler signal processing algorithm based on fewer frames and the elimination of flyback error caused by a sawtooth modulation signal at higher frequencies.

Tritiated adenosylcobalamin, labeled at the exchangeable position, has been used to investigate the partitioning of tritium between substrate and product in the reaction catalyzed by glutamate mutase. The isotope partitions between glutamate and methylaspartate in nearly 1:1 ratio, regardless of the direction in which the overall reaction is proceeding. This is consistent with a free-energy profile in which the interconversion of the intermediate glutamyl and methylaspartyl radicals is rapid relative to the transfer of tritium from 5'-deoxyadenosine to either substrate or product. Initial velocity measurements have been used to measure the tritium isotope effects for the transfer of tritium from adenosylcobalamin to product in each direction. The isotope effect is 21 for the formation of glutamate and 19 for the formation of methylasparate. The large magnitude of these isotope effects makes it likely that the rate-determining step may be altered by the substitution of tritium for hydrogen in the reaction. The results of these experiments are compared with previous isotope effect measurements made on other adenosylcobalamin-dependent enzymes.

Bullatacin, isolated from the fruit of Annona atemoya, is one of the most potentially effective antitumor annonaceous acetogenins. Bullatacin was studied here for its ability to inhibit the proliferation of 2.2.15 cells, hepatitis B virus (HBV) DNA transfected human hepatocarcinoma cell line. It was found that bullatacin induced cytotoxicity of 2.2.15 cells in a time- and dose-dependent manner. Fifty percent effective dose (ED50) on day 1 of exposure to bullatacin were 7.8 +/- 2.5 nM for 2.2.15 cells. [3H]-Thymidine incorporation assays showed almost the same results. Bullatacin-treatment also reduced concentrations of hepatitis B surface antigen (HBsAg) in the cultured medium released from 2.2.15 cells, coincident with the decrease in the cell proliferation. Analysis of mophological changes of bullatacin-treated 2.2.15 by inverted phase-contrast microscope and eletron microscopy revealed a possible model of action for bullatacin to inhibit proliferation of 2.2.15 cells by inducing apoptosis. Most of the bullatacin-induced cell death was found to be due to apoptosis, as determined by double staining with fluorescein-isothiocyanate (FITC)-labeled annexin V and propidium iodide (PI).

Between 1994 and 1998, 15 patients had corrective dome-shaped osteotomy of the humerus for posttraumatic cubitus varus deformity. Thirteen patients had surgery before puberty and two patients had surgery after puberty. In the prepuberty group, all the osteotomies were done by a posterior approach with triceps muscle splitting, and cross pins were used to fix the osteotomy. In the postpuberty group, the osteotomies were done by a posterior approach with olecranon osteotomy, and reconstructive plates were used for fixation. The average followup was 2 years and 4 months. Preoperative carrying angle ranged from 19 degrees to 31 degrees varus (average, 26.2 degrees) and postoperative carrying angle ranged from 7 degrees to 15 degrees valgus (average, 10.7 degrees). No loss of correction was observed and all osteotomies united. The preoperative and postoperative differences of the lateral condylar prominence index ranged from -67% to +6% (average, -30.1%). After reviewing these cases, a dome-shaped osteotomy was found to have the following advantages for correction of cubitus varus deformity: the osteotomy site is more stable than a lateral closing wedge osteotomy for maintaining the correction obtained; the domed osteotomy avoids having the lateral condyle becoming prominent; and the posterior scar is more cosmetically acceptable than the lateral scar in the lateral closing wedge osteotomy.

To establish the diagnostic criteria for hip joint effusion, the normal width of the anterior hip synovial recess in children and the difference between both hips of the same child were examined in this study. Eight kindergarten schools were randomly selected for study in Kaohsiung City. The width of anterior hip synovial recess of 1,568 hips in 784 children (421 boys, 363 girls) was measured by ultrasound scanner with 7.5-MHz linear probe. The age of children ranged from 2.5 to 6.6 years old. During measurement, the children were put in supine position with hips and knees in extension and patella facing up. The results revealed that the mean width of the anterior synovial recess was 7.29+/-1.15 mm. Linear correlation of the width of synovial recess to age and height was disclosed and expressed as follows: width (millimeters) equal to 6.52+0.013x age (months), or width (millimeters) equal to 3.97+0.030x height (centimeters). The mean difference between both hips of the same child was 0.611+/-0.523 mm, and the difference was independent from the factors of age, gender, height, or weight (p>0.05). Ninety-five percent of the differences should be < or =1.46 mm, so that if the difference between hips is >1.46 mm, hip joint effusion should be suspected.

Glutamate mutase catalyzes the reversible isomerization of L-glutamate to L-threo-3-methylaspartate. Rapid quench experiments have been performed to measure apparent rate constants for several chemical steps in the reaction. The formation of substrate radicals when the enzyme was reacted with either glutamate or methylaspartate was examined by measuring the rate at which 5'-deoxyadenosine was formed, and shown to be sufficiently fast for this step to be kinetically competent. Furthermore, the apparent rate constant for 5'-deoxyadenosine formation was very similar to that measured previously for cleavage of the cobalt-carbon bond of adenosylcobalamin by the enzyme, providing further support for a mechanism in which homolysis of the coenzyme is coupled to hydrogen abstraction from the substrate. The pre-steady-state rates of methylaspartate and glutamate formation were also investigated. No burst phase was observed with either substrate, indicating that product release does not limit the rate of catalysis in either direction. For the conversion of glutamate to methylaspartate, a single chemical step appeared to dominate the overall rate, whereas in the reverse direction a lag phase was observed, suggesting the accumulation of an intermediate, tentatively ascribed to glycyl radical and acrylate. The rates of formation and decay of this intermediate were also sufficiently rapid for it to be kinetically competent. When combined with information from previous mechanistic studies, these results allow a qualitative free energy profile to constructed for the reaction catalyzed by glutamate mutase.

An in-vivo model of New Zealand white rabbit was used to study the influence of gap size on the interfacial union between bone and tendon through histological observation and mechanical testing. In the model, the anterior cruciate ligament (ACL) was cut and reconstructed by autografted semitendinosus tendon (with average diameter of 1.48 mm +/- 0.12 mm). Mechanical testing of the interfacial healing tissue was done on the 15th post-operative day. At that time the mean maximal tensile strength was 2.511 +/- 0.293 kg to a bone tunnel size of 1.5 mm. The maximal tensile strength lowered to 1.853 +/- 0.563 kg to a bone tunnel size of 1.8 mm. The maximal tensile strength lowered to 1.302 +/- 0.657 kg to a bone tunnel size of 2.0 mm. Using a paired-t test, the gap size was found to have great influence on the tensile strength of the interfacial healing tissue (p < 0.05). The histological study showed that the interfacial gap was connected by the new growing collagen fibers. The healing tissue appeared much denser and much more maturated and organized in the smaller interfacial gap in comparison with specimens with a larger gap so that it can tolerate higher tensile strength. From this study, we concluded that the gap size really plays an important role in the process of maturation and organization of interfacial healing tissue. Furthermore, we recommend that in order to achieve greater anchoring strength of the grafted tendons, the bone tunnel should be made with approximately the same diameter of grafted tendon.

For early detection of the effusion of infected joint, 40 children were examined by ultrasound scanner for suspected septic arthritis. Thirty-one patients were found with joint effusion, and the needle aspirations of these 31 joints confirmed septic arthritis in 22 patients. In 3 patients, in addition to the joint effusion, the joint surrounding subperiosteal abscess and cortical erosion also were found on sonography, resulting in a diagnosis of concurrent osteomyelitis. In two patients, sonography confirmed only soft tissue swelling and abscess formation on the buttock, but without hip joint effusion. These findings excluded the diagnosis of septic arthritis and helped us obviate the unnecessary attempts at joint aspiration. In one patient, sonography revealed only flexor tenosynovitis without wrist joint effusion. This case was later treated by tenosynovectomy rather than wrist arthrotomy and the pathological examination showed to be a tuberculous tenosynovitis. From the preliminary results, we find ultrasonography has the following advantages for the diagnosis of septic arthritis: 1.) ultrasonography is very sensitive in detecting the joint effusion of septic arthritis; 2.) ultrasonography can clearly define the pathological extent of septic arthritis and help clinicians to treat the concurrent osteomyelitis by appropriate surgical debridement; and 3.) ultrasonography can differentiate soft tissue abscess or tenosynovitis from septic arthritis and help clinicians obviate unnecessary needle joint aspiration.

In order to study the factors related to Enterobius vermicularis infection among pre-school children in Ta-Liao District of Kaohsiung County, a questionnaire was designed to interview parents of preschool children selected by random sampling from 7 kindergartens in Ta-Liao District. Enterobius infections in the children were then examined by using two-consecutive-day adhesive cellophane paper perianal swabs. The effective sample numbered 555 children. Variables causing the infection among infected and non-infected children were analyzed by chi-square test and point-biserial correlation. The results indicated that there were significant relationship between infection and the follow items: having snacks; sucking fingers; size of house; ways of cleaning house; place of activities; parent's cognizing that anus is the polluted source of eggs; recognition of the cause-and-effect relationship between eating in the bedroom and being reinfected with Enterobius; recognition of preventing reinfection of Enterobius by taking a shower; and educational background of father. Through logistic regression analysis with backward selection, the authors constructed a predicting model which can predict the infection rate of E. vermicularis among pre-school children according to the habit of having snacks, the habit of sucking fingers, size of house, parent's recognizing that taking a shower can prevent people from reinfection, and the educational background of father.

"Ham-Hong-Chho" is a folk medicine in Taiwan, derived from the entire plants of Bidens pilosa L. var. minor (Blume) Sherff (Compositae), B. pilosa L. and B. chilensis DC. The anti-inflammatory effect of aqueous extracts of the three plants against paw edema induced by carrageenan and chronic arthritis induced by complete Freund's adjuvant were determined in rats. The results indicated that paw edema induced by carrageenan was significantly decreased by treatment with aqueous extracts (150 or 300 mg/kg) of all three plants (p < 0.05) and that the effect of Bidens pilosa var. minor was the most potent. However, only extracts (500 mg/kg) of B. pilosa L. var. minor and B. pilosa L. significantly decreased the paw edema induced by complete Freund's adjuvant (p < 0.05).