Fast quantum logic gates with trapped-ion qubits.

Quantum bits (qubits) based on individual trapped atomic ions are a promising technology for building a quantum computer. The elementary operations necessary to do so have been achieved with the required precision for some error-correction schemes. However, the essential two-qubit logic gate that is used to generate quantum entanglement has hitherto always been performed in an adiabatic regime (in which the gate is slow compared with the characteristic motional frequencies of the ions in the trap), resulting in logic speeds of the order of 10 kilohertz. There have been numerous proposals of methods for performing gates faster than this natural 'speed limit' of the trap. Here we implement one such method, which uses amplitude-shaped laser pulses to drive the motion of the ions along trajectories designed so that the gate operation is insensitive to the optical phase of the pulses. This enables fast (megahertz-rate) quantum logic that is robust to fluctuations in the optical phase, which would otherwise be an important source of experimental error. We demonstrate entanglement generation for gate times as short as 480 nanoseconds-less than a single oscillation period of an ion in the trap and eight orders of magnitude shorter than the memory coherence time measured in similar calcium-43 hyperfine qubits. The power of the method is most evident at intermediate timescales, at which it yields a gate error more than ten times lower than can be attained using conventional techniques; for example, we achieve a 1.6-microsecond-duration gate with a fidelity of 99.8 per cent. Faster and higher-fidelity gates are possible at the cost of greater laser intensity. The method requires only a single amplitude-shaped pulse and one pair of beams derived from a continuous-wave laser. It offers the prospect of combining the unrivalled coherence properties, operation fidelities and optical connectivity of trapped-ion qubits with the submicrosecond logic speeds that are usually associated with solid-state devices.

Scalable substrate development for aqueous sample preparation for atom probe tomography.

Reliable and consistent preparation of atom probe tomography (APT) specimens from aqueous and hydrated biological specimens remains a significant challenge. One particularly difficult process step is the use of a focused ion beam (FIB) instrument for preparing the required needle-shaped specimen, typically involving a 'lift-out' procedure of a small sample of material. Here, two alternative substrate designs are introduced that enable using FIB only for sharpening, along with example APT datasets. The first design is a laser-cut FIB-style half-grid close to those used for transmission electron microscopy (TEM) that can be used in a grid holder compatible with APT pucks. The second design is a larger, standalone self-supporting substrate called a 'crown', with several specimen positions, which self-aligns in APT pucks, prepared by electrical discharge machining (EDM). Both designs are made nanoporous, to provide strength to the liquid-substrate interface, using chemical and vacuum dealloying. Alpha brass, a simple, widely available, lower-cost alternative to previously proposed substrates, was selected for this work. The resulting designs and APT data are presented and suggestions are provided to help drive wider community adoption.

High-Rate, High-Fidelity Entanglement of Qubits Across an Elementary Quantum Network.

We demonstrate remote entanglement of trapped-ion qubits via a quantum-optical fiber link with fidelity and rate approaching those of local operations. Two ^{88}Sr^{+} qubits are entangled via the polarization degree of freedom of two spontaneously emitted 422 nm photons which are coupled by high-numerical-aperture lenses into single-mode optical fibers and interfere on a beam splitter. A novel geometry allows high-efficiency photon collection while maintaining unit fidelity for ion-photon entanglement. We generate heralded Bell pairs with fidelity 94% at an average rate 182 s^{-1} (success probability 2.18×10^{-4}).

Developing a theoretical maintenance model for disordered eating in Type 1 diabetes.

BACKGROUND: According to the literature, eating disorders are an increasing problem for more than a quarter of people with Type 1 diabetes and they are associated with accentuated diabetic complications. The clinical outcomes in this group when given standard eating disorder treatments are disappointing. The Medical Research Council guidelines for developing complex interventions suggest that the first step is to develop a theoretical model. AIM: To review existing literature to build a theoretical maintenance model for disordered eating in people with Type 1 diabetes. METHOD: The literature in diabetes relating to models of eating disorder (Fairburn's transdiagnostic model and the dual pathway model) and food addiction was examined and assimilated. RESULTS: The elements common to all eating disorder models include weight/shape concern and problems with mood regulation. The predisposing traits of perfectionism, low self-esteem and low body esteem and the interpersonal difficulties from the transdiagnostic model are also relevant to diabetes. The differences include the use of insulin mismanagement to compensate for breaking eating rules and the consequential wide variations in plasma glucose that may predispose to 'food addiction'. Eating disorder symptoms elicit emotionally driven reactions and behaviours from others close to the individual affected and these are accentuated in the context of diabetes. CONCLUSION: The next stage is to test the assumptions within the maintenance model with experimental medicine studies to facilitate the development of new technologies aimed at increasing inhibitory processes and moderating environmental triggers.

Enabling near-atomic-scale analysis of frozen water.

Transmission electron microscopy went through a revolution enabling routine cryo-imaging of biological and (bio)chemical systems, in liquid form. Yet, these approaches typically lack advanced analytical capabilities. Here, we used atom probe tomography to analyze frozen liquids in three dimensions with subnanometer resolution. We introduce a specimen preparation strategy using nanoporous gold. We report data on 2- to 3-µm-thick layers of ice formed from both high-purity deuterated water and a solution of 50 mM NaCl in high-purity deuterated water. The analysis of the gold-ice interface reveals a substantial increase in the solute concentrations across the interface. We explore a range of experimental parameters to show that atom probe analyses of bulk aqueous specimens come with their own challenges and discuss physical processes that produce the observed phenomena. Our study demonstrates the viability of using frozen water as a carrier for near-atomic-scale analysis of objects in solution by atom probe tomography.

Preliminary investigation of a multimodal enhanced brain function index among high school and collegiate concussed male and female athletes.

Objective: The primary purpose of this study was to examine the longitudinal effects of sports-related concussion (SRC) on a multi-faceted assessment battery which included neuropsychological testing, symptom reporting, and enhanced brain function index (eBFI) among athletes with and without SRC. A secondary purpose was to explore longitudinal sex differences among these measures in athletes with and without SRC. Methods: A case-control, repeated-measures design was used for this study. A total of 186 athletes (concussed group:n= 87 controls:n= 99) participated in the study. A repeated-measures design was used in which each athlete was tested at four time points following an SRC: within 72 h of injury (Day 0; 2.0 ± 0.9 days following injury), 5 days following injury (Day 5; 5.0 ± 0.0), at return to play (RTP; 18.3 ± 13.8 days following injury), and within 45 days following RTP (RTP45; 66.2 ± 19.0 days following injury). All analyses were conducted separately using a 2 (Group: concussed, control) × 2 (Sex: male, female) × 4 (Time:Day 0, Day 5, RTP, RTP45) univariate multi-level model including the random intercept for each participant. A higher eBFI score indicates a better performance. Alpha level was set aprior at .05. This study was registered on clinicaltrials.gov (Objective Brain Function Assessment of mTBI/Concussion in College/high school Athletes NCT02477943, NCT02661633, CAS 13-25 NCT03963804). Results: Concussed athletes exhibited impaired eBFI within 72 h of SRC and at Day 5 compared to controls (p<.001). Analysis of eBFI scores between male and female athletes revealed a main effect of sex (p=.05), with female athletes exhibiting lower eBFI (33.9 ± 30.7) relative to male athletes (40.4 ± 33.0), however, it did not indicate interactions between sex, group, and time (p's ≥ 0.786). Conclusion: The eBFI appears to be a useful tool in determining concussed athletes during the acute stages of an SRC. However, this index may lack the sensitivity to detect sex-related differences between groups at various time points during recovery.

Skeletal muscle as the potential power source for a cardiovascular pump: assessment in vivo.

Skeletal muscle ventricles (SMVs) were constructed from canine latissimus dorsi and connected to a totally implantable mock circulation device. The SMVs, stimulated by an implantable pulse generator, pumped continuously for up to 8 weeks in free-running beagle dogs. Systolic pressures produced by the SMVs, initially of 139 +/- 7.2 mmHg and after 1 month of continuous pumping of 107 +/- 7 mmHg, were comparable to normal physiologic pressures in the adult beagles (114 +/- 21 mmHg). After 2 weeks of continuous pumping, the mean stroke work of the SMVs was 0.4 X 10(6) ergs, a performance that compares favorably with the animal's cardiac ventricles. This study shows that canine skeletal muscle which has not received prior training or electrical conditioning can perform sustained work at the high levels needed for an auxiliary cardiovascular pump. It might be possible eventually to use such muscle pumps in humans to assist the failing circulation and to provide support in children with certain types of congenital heart defects.

Advance decision-making in mental health - Suggestions for legal reform in England and Wales.

This paper argues that existing English and Welsh mental health legislation (The Mental Health Act 1983 (MHA)) should be changed to make provision for advance decision-making (ADM) within statute and makes detailed recommendations as to what should constitute this statutory provision. The recommendations seek to enable a culture change in relation to written statements made with capacity such that they are developed within mental health services and involve joint working on mental health requests as well as potential refusals. In formulating our recommendations, we consider the historical background of ADM, similarities and differences between physical and mental health, a taxonomy of ADM, the evidence base for mental health ADM, the ethics of ADM, the necessity for statutory ADM and the possibility of capacity based 'fusion' law on ADM. It is argued that the introduction of mental health ADM into the MHA will provide clarity within what has become a confusing area and will enable and promote the development and realisation of ADM as a form of self-determination. The paper originated as a report commissioned by, and submitted to, the UK Government's 2018 Independent Review of the Mental Health Act 1983.

A short response time atomic source for trapped ion experiments.

Ion traps are often loaded from atomic beams produced by resistively heated ovens. We demonstrate an atomic oven which has been designed for fast control of the atomic flux density and reproducible construction. We study the limiting time constants of the system and, in tests with 40Ca, show that we can reach the desired level of flux in 12 s, with no overshoot. Our results indicate that it may be possible to achieve an even faster response by applying an appropriate one-off heat treatment to the oven before it is used.

Role of changes in insulin and glucagon in glucose homeostasis in exercise.

This experiment was performed to determine if plasma glucose homeostasis is maintained in normal human volunteers during light exercise (40% maximal oxygen consumption [VO2 max]) when changes in insulin and glucagon are prevented. Hormonal control was achieved by the infusion of somatostatin, insulin, and glucagon. Glucose kinetics and oxidation rates were determined with stable isotopic tracers of glucose, and by indirect calorimetry. Two different rates of replacement of insulin and glucagon were used; in one group, insulin was clamped at 19.8 +/- 2.6 microU/ml (high-insulin group), and in the other group insulin was clamped at 9.2 +/- 1.3 microU/ml (low-insulin group). Glucagon was maintained at 261 +/- 16.2 and 124 +/- 6.4 pg/ml, respectively, in the high-insulin and low-insulin groups. Without hormonal control, plasma glucose homeostasis was maintained during exercise because the increase in glucose uptake was balanced by a corresponding increase in glucose production. When changes in insulin and glucagon were prevented, plasma glucose concentration fell, particularly in the high-insulin group. Glucose uptake increased to a greater extent than when hormones were not controlled, and glucose production did not increase sufficiently to compensate. The increase in glucose uptake in the hormonal control groups was associated with an increased rate of glucose oxidation. When euglycemia was maintained by glucose infusion in the hormonal control subjects, the modest increase in glucose production that otherwise occurred was prevented. It is concluded that during light exercise there must be a reduction in insulin concentration and/or an increase in glucagon concentration if plasma glucose homeostasis is to be maintained. If such changes do not occur, hypoglycemia, and hence exhaustion, may occur.

Mammalian nonsense codons can be cis effectors of nuclear mRNA half-life.

Frameshift and nonsense mutations within the gene for human triosephosphate isomerase (TPI) that generate a nonsense codon within the first three-fourths of the protein coding region have been found to reduce the abundance of the product mRNA that copurifies with nuclei. The cellular process and location of the nonsense codon-mediated reduction have proven difficult to elucidate for technical reasons. We show here, using electron microscopy to judge the purity of isolated nuclei, that the previously established reduction to 25% of the normal mRNA level is evident for nuclei that are free of detectable cytoplasmic contamination. Therefore, the reduction is likely to be characteristic of bona fide nuclear RNA. Fully spliced nuclear mRNA is identified by Northern (RNA) blot hybridization and a reverse transcription-PCR assay as the species that undergoes decay in experiments that used the human c-fos promoter to elicit a burst and subsequent shutoff of TPI gene transcription upon the addition of serum to serum-deprived cells. Finally, the finding that deletion of a 5' splice site of the TPI gene results predominantly but not exclusively in the removal by splicing (i.e., skipping) of the upstream exon as a part of the flanking introns has been used to demonstrate that decay is specific to those mRNA products that maintain the nonsense codon. This result, together with our previous results that implicate translation by ribosomes and charged tRNAs in the decay mechanism, indicate that nonsense codon recognition takes place after splicing and triggers decay solely in cis. The possibility that decay takes place during the process of mRNA export from the nucleus to the cytoplasm is discussed.

Evidence for the existence of a single enzyme catalyzing the phosphorylation of choline and ethanolamine in primate lung.

Choline kinase (ATP:choline phosphotransferase, EC 2.7.1.32) has been isolated and purified 1000-fold from adult African Green monkey lung with a yield of 10%. The purified enzyme also phosphorylated ethanolamine (ratio of ethanolamine kinase to choline kinase = 0.30). This ratio remained constant throughout the purification procedure. The Km for choline (3.0 - 10(-5) M) was lower than that of ethanolamine (1.2 - 10(-3) M.) Choline was also found to inhibit ethanolamine kinase activity by 50% at a concentration of 0.005 mM, while ethanolamine inhibited choline only at very high concentrations (100--150 mM). When the enzyme was subjected to inactivation by heat, hemicholinium-3, trypsin digestion, and p-hydroxymercuribenzoate, both ethanolamine kinase and choline kinase activities were destroyed at the same rate. Freezing and thawing in the absence of glycerol also destroyed both activities at the same rate. Based on these findings, we conclude that in adult African Green monkey lung tissue, there is only one enzyme for the phosphorylation of ethanolamine and choline, and that choline phosphorylation predominates.

Origin of the left coronary artery from the right pulmonary artery.

Origin of the left coronary artery from the right pulmonary artery has rarely been documented. This is the first such case in a heart with an intact ventricular septum and paraductal coarctation of the aorta. Although an antemortem diagnosis was made and the anomalous left coronary artery was ligated, the patient, a 3 1/2 month old infant, died 1 day after surgery. Autopsy confirmed the diagnosis, but revealed that the left coronary artery was dominant. It is believed that the fatal outcome in the infant was, in part, due to the dominance of the left coronary artery and the effects of the coarctation on the already ischemic left ventricle.

Coronary-bronchial artery fistula with partial absence of a pulmonary artery: association with partial anomalous pulmonary venous drainage.

A patient is presented with partial absence of the right pulmonary artery, left coronary artery to bronchial artery fistula and systemic arterial desaturation with a patent foramen ovale. The various aspects of the syndrome are discussed and the rationale for nonoperative closure of the foramen is described.

Lymphokine-dependent proliferation of T-lymphoid cells: regulated responsiveness and role in vivo.

The discovery of lymphokines stemmed from their ability to promote T-lymphocyte proliferation in vitro. Even after 20 years of intensive investigation, crucial aspects remain to be clarified about the role of specific lymphokines in T-cell proliferation and the biochemical mechanisms by which they play these roles, particularly in vivo. The present review focuses on conventional populations of TCR(alpha)beta T cells. Older findings and new insights into the function of specific lymphokines in T-lymphocyte proliferation in vivo are summarized along with unanswered questions raised by these observations. Vital contributions of lymphokines to clonal proliferation arise from two processes: the protection of cells against apoptosis and the activation of cell cycling. Findings are underscored indicating that the activity of a particular lymphokine depends on the subset of T cells (CD4 vs. CD8; naive vs. memory) to which it binds, and that point to potential pitfalls of extrapolating from tissue culture-adapted models to the regulation of T cells in vivo. After summaries of signaling mechanisms related to the proliferative activity of lymphokines, recent findings are highlighted suggesting that such signaling is a regulated and plastic process rather than one fixed schema of action.

An oral fluid test for syphilis.

We have developed a time-resolved fluorescence immunoassay to detect antibodies to Treponema pallidum recombinant antigens in oral fluid specimens. Using an 'Oracol' swab, oral fluid was collected from 34 subjects with a serological diagnosis of syphilis and 97 seronegative controls. Using a cut-off of three standard deviations over control mean, the sensitivity and specificity of the assay in all subjects with positive syphilis serology was 76.5% and 97.9%, respectively. In those with early syphilis, the sensitivity and specificity of the assay was 100% and 97.9%. In a non-outbreak situation, screening clinic attendees for syphilis using oral fluid specimens is potentially useful when collection of blood is not practicable. In addition, it may have much to offer in outreach projects and epidemiological investigations.

Use of skeletal muscle grafts for cardiac assist.

Skeletal muscle is a potential power source for cardiac assist. Two approaches have been used to harvest this power: dynamic cardiomyoplasty, which involves the application of a muscle directly to the heart to support cardiac contractile function; and the construction of skeletal muscle pouches or ventricles, which are used as separate pumps working either in parallel or in series with the heart. These techniques may represent an alternate therapeutic approach in patients with end-stage heart disease or in infants with certain congenital heart anomalies.

Rapid and portable methods of lactose tolerance test administration.

Abbreviated, portable methods of lactose tolerance test administration were investigated. Results obtained with the Ames Reflectance Meter/Dextrostix system for blood glucose determination during lactose tolerance testing were compared with those obtained from a standard method, the AutoAnalyzer. Subjects who had maximum blood glucose rises below 20 mg/100 ml were considered to have a flat lactose tolerance curve and were designated lactose nondigesters. Results of the two methods were very similar for determination of maximum rise in blood sugar over fasting level, for obtaining values of individual blood sugar determinations, and for diagnosis of lactose nondigesters. The effect of omission of the final blood sample on tolerance test results was examined. It was found that maximum rises in blood glucose occurred before the final sample in 31 of 35 cases on the AutoAnalyzer and in 26 of 27 cases on the Reflectance Meter. In no case did omission of the final sample change the results of the lactose tolerance test.

Relationships between Ascaris infection and growth of malnourished preschool children in Kenya.

A longitudinal study in Ascaris-infected and noninfected children was conducted in two Kenyan villages. Anthropometric, clinical, and stool exams were performed three times at 14-week intervals. All children received an anthelmintic drug (levamisole) at the second examination. In the 14 weeks before deworming, children with Ascaris (n = 61) did not differ from controls (n = 125) in percentage expected weight gain. In the 14 weeks after deworming, previously infected children showed higher percentage expected weight gain than controls. Before deworming, there was a statistically significant (P less than 0.0005) decrease in triceps skinfold thickness in Ascaris-infected children versus controls. After deworming, skinfold increased significantly (P less than 0.0005) in previously infected children versus controls. Multiple regression analysis showed that Ascaris infection was by far the most important variable of those studied explaining decrease in skinfold thickness before and increase after deworming. It appears that even light Ascaris infections might adversely influence nutritional status, and deworming might enhance growth.