A two-site Kitaev chain in a two-dimensional electron gas.

Artificial Kitaev chains can be used to engineer Majorana bound states (MBSs) in superconductor-semiconductor hybrids1-4. In this work, we realize a two-site Kitaev chain in a two-dimensional electron gas by coupling two quantum dots through a region proximitized by a superconductor. We demonstrate systematic control over inter-dot couplings through in-plane rotations of the magnetic field and via electrostatic gating of the proximitized region. This allows us to tune the system to sweet spots in parameter space, where robust correlated zero-bias conductance peaks are observed in tunnelling spectroscopy. To study the extent of hybridization between localized MBSs, we probe the evolution of the energy spectrum with magnetic field and estimate the Majorana polarization, an important metric for Majorana-based qubits5,6. The implementation of a Kitaev chain on a scalable and flexible two-dimensional platform provides a realistic path towards more advanced experiments that require manipulation and readout of multiple MBSs.

Evidence of topological superconductivity in planar Josephson junctions.

Majorana zero modes-quasiparticle states localized at the boundaries of topological superconductors-are expected to be ideal building blocks for fault-tolerant quantum computing1,2. Several observations of zero-bias conductance peaks measured by tunnelling spectroscopy above a critical magnetic field have been reported as experimental indications of Majorana zero modes in superconductor-semiconductor nanowires3-8. On the other hand, two-dimensional systems offer the alternative approach of confining Majorana channels within planar Josephson junctions, in which the phase difference φ between the superconducting leads represents an additional tuning knob that is predicted to drive the system into the topological phase at lower magnetic fields than for a system without phase bias9,10. Here we report the observation of phase-dependent zero-bias conductance peaks measured by tunnelling spectroscopy at the end of Josephson junctions realized on a heterostructure consisting of aluminium on indium arsenide. Biasing the junction to φ ≈ π reduces the critical field at which the zero-bias peak appears, with respect to φ = 0. The phase and magnetic-field dependence of the zero-energy states is consistent with a model of Majorana zero modes in finite-size Josephson junctions. As well as providing experimental evidence of phase-tuned topological superconductivity, our devices are compatible with superconducting quantum electrodynamics architectures11 and are scalable to the complex geometries needed for topological quantum computing9,12,13.

Control of Andreev Bound States Using Superconducting Phase Texture.

Andreev bound states with opposite phase-inversion asymmetries are observed in local tunneling spectra at the two ends of a superconductor-semiconductor-superconductor planar Josephson junction in the presence of a perpendicular magnetic field, while the nonlocal spectra remain phase symmetric. Spectral signatures agree with a theoretical model, yielding a physical picture in which phase textures in superconducting leads localize and control the position of Andreev bound states in the junction, demonstrating a simple means of controlling the position and size of Andreev states within a planar junction.

Phase Asymmetry of Andreev Spectra from Cooper-Pair Momentum.

In analogy to conventional semiconductor diodes, the Josephson diode exhibits superconducting properties that are asymmetric in applied bias. The effect has been investigated in a number of systems recently, and requires a combination of broken time-reversal and inversion symmetries. We demonstrate a dual of the usual Josephson diode effect, a nonreciprocal response of Andreev bound states to a superconducting phase difference across the normal region of a superconductor-normal-superconductor Josephson junction, fabricated using an epitaxial InAs/Al heterostructure. Phase asymmetry of the subgap Andreev spectrum is absent in the absence of in-plane magnetic field and reaches a maximum at 0.15 T applied in the plane of the junction transverse to the current direction. We interpret the phase diode effect in this system as resulting from finite-momentum Cooper pairing due to orbital coupling to the in-plane magnetic field. At higher magnetic fields, we observe a sign reversal of the diode effect that appears together with a reopening of the spectral gap. Within our model, the sign reversal of the diode effect at higher fields is correlated with a topological phase transition that requires Zeeman and spin-orbit interactions in addition to orbital coupling.

Controlling Andreev Bound States with the Magnetic Vector Potential.

Tunneling spectroscopy measurements are often used to probe the energy spectrum of Andreev bound states (ABSs) in semiconductor-superconductor hybrids. Recently, this spectroscopy technique has been incorporated into planar Josephson junctions (JJs) formed in two-dimensional electron gases, a potential platform to engineer phase-controlled topological superconductivity. Here, we perform ABS spectroscopy at the two ends of planar JJs and study the effects of the magnetic vector potential on the ABS spectrum. We show that the local superconducting phase difference arising from the vector potential is equal in magnitude and opposite in sign at the two ends, in agreement with a model that assumes localized ABSs near the tunnel barriers. Complemented with microscopic simulations, our experiments demonstrate that the local phase difference can be used to estimate the relative position of localized ABSs separated by a few hundred nanometers.

Bilinear Magnetoresistance in HgTe Topological Insulator: Opposite Signs at Opposite Surfaces Demonstrated by Gate Control.

Spin-orbit effects appearing in topological insulators (TI) and at Rashba interfaces are currently revolutionizing how we can manipulate spins and have led to several newly discovered effects, from spin-charge interconversion and spin-orbit torques to novel magnetoresistance phenomena. In particular, a puzzling magnetoresistance has been evidenced as bilinear in electric and magnetic fields. Here, we report the observation of bilinear magnetoresistance (BMR) in strained HgTe, a prototypical TI. We show that both the amplitude and sign of this BMR can be tuned by controlling with an electric gate the relative proportions of the opposite contributions of opposite surfaces. At magnetic fields of 1 T, the magnetoresistance is of the order of 1% and has a larger figure of merit than previously measured TIs. We propose a theoretical model giving a quantitative account of our experimental data. This phenomenon, unique to TI, offers novel opportunities to tune their electrical response for spintronics.

Developing and validating a comprehensive measure of coordination in patient aligned care teams.

BACKGROUND/OBJECTIVE: Despite numerous extant measures assessing context-specific elements of care coordination, we are unaware of any comprehensive, team-based instrument that measures the requisite mechanisms and conditions required to coordinate successfully. In this study we develop and validate the psychometric properties of the Coordination Practices Survey, a context-agnostic measure of coordination for primary care teams. METHODS: Coordination items were developed based on a systematic literature review; items from previously developed scales were adapted and new items were created as needed; all items were refined after subject matter expert review and feedback. We collected data from Primary Care teams drawn from 1200 Veterans Health Administration (VHA) medical centers and outpatient clinics nationwide. 1645 primary care team members from 512 patient aligned care teams in the Veterans Health Administration completed the survey from 2015 to 2016. Psychometric properties were assessed after data collection using Cronbach's alpha, intraclass correlations and multilevel confirmatory factor analysis to assess the factor structure. RESULTS: Our findings confirmed the psychometric properties of two distinguishable subscales of coordination: (a) Accountability and (b) Common Understanding. The within- and between-team latent structure of each subscale exhibited adequate fit to the data, as well as appropriately high Cronbach's alpha and intraclass correlations. There was insufficient variability in responses to the predictability subscale to properly assess its psychometric properties. CONCLUSION: With context-specific validation, our subscales of accountability and common understanding may be used to assess coordination processes in other contexts for both research and operational applications.

InSbAs Two-Dimensional Electron Gases as a Platform for Topological Superconductivity.

Topological superconductivity can be engineered in semiconductors with strong spin-orbit interaction coupled to a superconductor. Experimental advances in this field have often been triggered by the development of new hybrid material systems. Among these, two-dimensional electron gases (2DEGs) are of particular interest due to their inherent design flexibility and scalability. Here, we discuss results on a 2D platform based on a ternary 2DEG (InSbAs) coupled to in situ grown aluminum. The spin-orbit coupling in these 2DEGs can be tuned with the As concentration, reaching values up to 400 meV Å, thus exceeding typical values measured in its binary constituents. In addition to a large Landé g-factor of ∼55 (comparable to that of InSb), we show that the clean superconductor-semiconductor interface leads to a hard induced superconducting gap. Using this new platform, we demonstrate the basic operation of phase-controllable Josephson junctions, superconducting islands, and quasi-1D systems, prototypical device geometries used to study Majorana zero modes.

Factors Influencing the Early Development of World-Class Caribbean Track and Field Athletes: A Qualitative Investigation.

This qualitative investigation sought to explore through a socio-cultural lens the perceived early training and competition environment, and support network of world-class Caribbean track and field athletes and the influence on their sport engagement and progression during early childhood and adolescence. Sixteen world-class track and field athletes (8 males and 8 females; M age = 29, SD = 5 years) from 6 English-speaking Caribbean islands took part in semi-structured interviews. A thematic analysis was performed on the transcribed data. Three superordinate themes were identified as key factors that influenced the early sporting development of world-class Caribbean athletes: (1) conducive sporting environment, (2) functional social support network, and (3) key organizational input. Findings revealed that perceived high levels of deliberate play activity in childhood (6 - 12 years) and an intense track and field competition culture in adolescence (13 - 20 years) were conducive to the continued engagement and progression of world-class Caribbean track and field athletes at the junior level. Furthermore, world-class athletes perceived themselves to be positively influenced by the support received from their immediate social support network and key organizations during this period. This study showed that a conducive sporting environment coupled with optimal social and organizational support may have encouraged world-class Caribbean athletes to remain engaged in track and field and to successfully progress within the sport at the junior level. Findings shed light on the sporting culture at the junior level within the Caribbean region and provide insight into key environmental factors that can influence and foster the development of future World Champions and Olympians.

A Systematic Literature Review of Instruments to Measure Coordination.

EXECUTIVE SUMMARY: Organizing patient care and improving team coordination have been identified by the Institute of Medicine and the Agency for Healthcare Research and Quality as essential components of high-quality care. Research is lacking, however, on the measurement of care team coordination and its mechanisms. Using an organizational psychology framework developed by Okhuysen and Bechky (O&B) as a guide, the authors identify strengths and gaps in the existing literature related to the measurement of coordination and its associated constructs. The authors conducted a review of peer-reviewed articles in healthcare, management, and psychology journals that contain survey items that could be used to measure the domains in the O&B framework. An initial search yielded 468 articles published from 1978 to 2014, 37 of which came from healthcare journals. From this set, 1,401 candidate survey items were extracted from 74 articles. Of these, 279 items were categorized into at least one O&B domain. Retained items were drawn from scales representing 51 constructs related to teamwork, roles, trust, coordination broadly, and ancillary constructs. Two constructs, physical proximity and plans and rules, were directly represented both in the O&B framework and as standalone constructs in the literature. The remaining constructs contributed items that indirectly assess components of the O&B framework domains. Despite decades of research on coordination, valid survey items for measuring the mechanisms and integrating conditions described by the O&B framework as leading to successful team coordination are scarce, and virtually nonexistent in healthcare, as measures of care team coordination.

Scaling of Majorana Zero-Bias Conductance Peaks.

We report an experimental study of the scaling of zero-bias conductance peaks compatible with Majorana zero modes as a function of magnetic field, tunnel coupling, and temperature in one-dimensional structures fabricated from an epitaxial semiconductor-superconductor heterostructure. Results are consistent with theory, including a peak conductance that is proportional to tunnel coupling, saturates at 2e^{2}/h, decreases as expected with field-dependent gap, and collapses onto a simple scaling function in the dimensionless ratio of temperature and tunnel coupling.

Loss of myocardial retinoic acid receptor α induces diastolic dysfunction by promoting intracellular oxidative stress and calcium mishandling in adult mice.

Retinoic acid receptor (RAR) has been implicated in pathological stimuli-induced cardiac remodeling. To determine whether the impairment of RARα signaling directly contributes to the development of heart dysfunction and the involved mechanisms, tamoxifen-induced myocardial specific RARα deletion (RARαKO) mice were utilized. Echocardiographic and cardiac catheterization studies showed significant diastolic dysfunction after 16wks of gene deletion. However, no significant differences were observed in left ventricular ejection fraction (LVEF), between RARαKO and wild type (WT) control mice. DHE staining showed increased intracellular reactive oxygen species (ROS) generation in the hearts of RARαKO mice. Significantly increased NOX2 (NADPH oxidase 2) and NOX4 levels and decreased SOD1 and SOD2 levels were observed in RARαKO mouse hearts, which were rescued by overexpression of RARα in cardiomyocytes. Decreased SERCA2a expression and phosphorylation of phospholamban (PLB), along with decreased phosphorylation of Akt and Ca2+/calmodulin-dependent protein kinase II δ (CaMKII δ) was observed in RARαKO mouse hearts. Ca2+ reuptake and cardiomyocyte relaxation were delayed by RARα deletion. Overexpression of RARα or inhibition of ROS generation or NOX activation prevented RARα deletion-induced decrease in SERCA2a expression/activation and delayed Ca2+ reuptake. Moreover, the gene and protein expression of RARα was significantly decreased in aged or metabolic stressed mouse hearts. RARα deletion accelerated the development of diastolic dysfunction in streptozotocin (STZ)-induced type 1 diabetic mice or in high fat diet fed mice. In conclusion, myocardial RARα deletion promoted diastolic dysfunction, with a relative preserved LVEF. Increased oxidative stress have an important role in the decreased expression/activation of SERCA2a and Ca2+ mishandling in RARαKO mice, which are major contributing factors in the development of diastolic dysfunction. These data suggest that impairment of cardiac RARα signaling may be a novel mechanism that is directly linked to pathological stimuli-induced diastolic dysfunction.

Cardiac-specific suppression of NF-κB signaling prevents diabetic cardiomyopathy via inhibition of the renin-angiotensin system.

Activation of NF-κB signaling in the heart may be protective or deleterious depending on the pathological context. In diabetes, the role of NF-κB in cardiac dysfunction has been investigated using pharmacological approaches that have a limitation of being nonspecific. Furthermore, the specific cellular pathways by which NF-κB modulates heart function in diabetes have not been identified. To address these questions, we used a transgenic mouse line expressing mutated IκB-α in the heart (3M mice), which prevented activation of canonical NF-κB signaling. Diabetes was developed by streptozotocin injections in wild-type (WT) and 3M mice. Diabetic WT mice developed systolic and diastolic cardiac dysfunction by the 12th week, as measured by echocardiography. In contrast, cardiac function was preserved in 3M mice up to 24 wk of diabetes. Diabetes induced an elevation in cardiac oxidative stress in diabetic WT mice but not 3M mice compared with nondiabetic control mice. In diabetic WT mice, an increase in the phospholamban/sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 ratio and decrease in ryanodine receptor expression were observed, whereas diabetic 3M mice showed an opposite effect on these parameters of Ca(2+) handling. Significantly, renin-angiotensin system activity was suppressed in diabetic 3M mice compared with an increase in WT animals. In conclusion, these results demonstrate that inhibition of NF-κB signaling in the heart prevents diabetes-induced cardiac dysfunction through preserved Ca(2+) handling and inhibition of the cardiac renin-angiotensin system.

Angiotensin type 1a receptor-deficient mice develop diabetes-induced cardiac dysfunction, which is prevented by renin-angiotensin system inhibitors.

BACKGROUND: Diabetes-induced organ damage is significantly associated with the activation of the renin-angiotensin system (RAS). Recently, several studies have demonstrated a change in the RAS from an extracellular to an intracellular system, in several cell types, in response to high ambient glucose levels. In cardiac myocytes, intracellular angiotensin (ANG) II synthesis and actions are ACE and AT1 independent, respectively. However, a role of this system in diabetes-induced organ damage is not clear. METHODS: To determine a role of the intracellular ANG II in diabetic cardiomyopathy, we induced diabetes using streptozotocin in AT1a receptor deficient (AT1a-KO) mice to exclude any effects of extracellular ANG II. Further, diabetic animals were treated with a renin inhibitor aliskiren, an ACE inhibitor benazeprilat, and an AT1 receptor blocker valsartan. RESULTS: AT1a-KO mice developed significant diastolic and systolic dysfunction following 10 wks of diabetes, as determined by echocardiography. All three drugs prevented the development of cardiac dysfunction in these animals, without affecting blood pressure or glucose levels. A significant down regulation of components of the kallikrein-kinin system (KKS) was observed in diabetic animals, which was largely prevented by benazeprilat and valsartan, while aliskiren normalized kininogen expression. CONCLUSIONS: These data indicated that the AT1a receptor, thus extracellular ANG II, are not required for the development of diabetic cardiomyopathy. The KKS might contribute to the beneficial effects of benazeprilat and valsartan in diabetic cardiomyopathy. A role of intracellular ANG II is suggested by the inhibitory effects of aliskiren, which needs confirmation in future studies.

Direct renin inhibition prevents cardiac dysfunction in a diabetic mouse model: comparison with an angiotensin receptor antagonist and angiotensin-converting enzyme inhibitor.

Hyperglycaemia up-regulates intracellular AngII (angiotensin II) production in cardiac myocytes, effects of which are blocked more effectively by renin inhibition than ARBs (angiotensin receptor blockers) or ACEis (angiotensin-converting enzyme inhibitors). In the present study, we determined whether renin inhibition is more effective at preventing diabetic cardiomyopathy than an ARB or ACEi. Diabetes was induced in adult mice for 10 weeks by STZ (streptozotocin). Diabetic mice were treated with insulin, aliskiren (a renin inhibitor), benazeprilat (an ACEi) or valsartan (an ARB) via subcutaneous mini-pumps. Significant impairment in diastolic and systolic cardiac functions was observed in diabetic mice, which was completely prevented by all three RAS (renin-angiotensin system) inhibitors. Hyperglycaemia significantly increased cardiac oxidative stress and circulating inflammatory cytokines, which were blocked by aliskiren and benazeprilat, whereas valsartan was partially effective. Diabetes increased cardiac PRR (prorenin receptor) expression and nuclear translocation of PLZF (promyelocytic zinc finger protein), which was completely prevented by aliskiren and valsartan, and partially by benazeprilat. Renin inhibition provided similar protection of cardiac function to ARBs and ACEis. Activation of PLZF by PRR represented a novel mechanism in diabetic cardiomyopathy. Differential effects of the three agents on oxidative stress, cytokines and PRR expression suggested subtle differences in their mechanisms of action.

Triplet correlations in Cooper pair splitters realized in a two-dimensional electron gas.

Cooper pairs occupy the ground state of superconductors and are typically composed of maximally entangled electrons with opposite spin. In order to study the spin and entanglement properties of these electrons, one must separate them spatially via a process known as Cooper pair splitting (CPS). Here we provide the first demonstration of CPS in a semiconductor two-dimensional electron gas (2DEG). By coupling two quantum dots to a superconductor-semiconductor hybrid region we achieve efficient Cooper pair splitting, and clearly distinguish it from other local and non-local processes. When the spin degeneracy of the dots is lifted, they can be operated as spin-filters to obtain information about the spin of the electrons forming the Cooper pair. Not only do we observe a near perfect splitting of Cooper pairs into opposite-spin electrons (i.e. conventional singlet pairing), but also into equal-spin electrons, thus achieving triplet correlations between the quantum dots. Importantly, the exceptionally large spin-orbit interaction in our 2DEGs results in a strong triplet component, comparable in amplitude to the singlet pairing. The demonstration of CPS in a scalable and flexible platform provides a credible route to study on-chip entanglement and topological superconductivity in the form of artificial Kitaev chains.

Cardiac-specific genetic inhibition of nuclear factor-κB prevents right ventricular hypertrophy induced by monocrotaline.

Uncontrolled pulmonary arterial hypertension (PAH) results in right ventricular (RV) hypertrophy (RVH), progressive RV failure, and low cardiac output leading to increased morbidity and mortality (McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J. J Am Coll Cardiol 53: 1573-1619, 2009). Although the exact figures of its prevalence are difficult to obtain because of the diversity of identifiable causes, it is estimated that the incidence of pulmonary hypertension is seven to nine cases per million persons in the general population and is most prevalent in the age group of 20-40, occurring more commonly in women than in men (ratio: 1.7 to 1; Rubin LJ. N Engl J Med 336: 111-117, 1997). PAH is characterized by dyspnea, chest pain, and syncope. Unfortunately, there is no cure for this disease and medical regimens are limited (Simon MA. Curr Opin Crit Care 16: 237-243, 2010). PAH leads to adverse remodeling that results in RVH, progressive right heart failure, low cardiac output, and ultimately death if left untreated (Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, Rabinovitch M. J Am Coll Cardiol 43: 13S-24S, 2004; Humbert M, Sitbon O, Simonneau G. N Engl J Med 351: 1425-1436, 2004. LaRaia AV, Waxman AB. South Med J 100: 393-399, 2007). As there are no direct tools to assess the onset and progression of PAH and RVH, the disease is often detected in later stages marked by full-blown RVH, with the outcome predominantly determined by the level of increased afterload (D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, et al. Ann Intern Med 115: 343-349, 1991; Sandoval J, Bauerle O, Palomar A, Gomez A, Martinez-Guerra ML, Beltran M, Guerrero ML. Validation of a prognostic equation Circulation 89: 1733-1744, 1994). Various studies have been performed to assess the genetic, biochemical, and morphological components that contribute to PAH. Despite major advances in the understanding of the pathogenesis of PAH, the molecular mechanism(s) by which PAH promotes RVH and cardiac failure still remains elusive. Of all the mechanisms involved in the pathogenesis, inflammation and oxidative stress remain the core of the etiology of PAH that leads to development of RVH (Dorfmüller P, Perros F, Balabanian K, Humbert M. Eur Respir J 22: 358-363, 2003).

Intracardiac intracellular angiotensin system in diabetes.

The renin-angiotensin system (RAS) has mainly been categorized as a circulating and a local tissue RAS. A new component of the local system, known as the intracellular RAS, has recently been described. The intracellular RAS is defined as synthesis and action of ANG II intracellularly. This RAS appears to differ from the circulating and the local RAS, in terms of components and the mechanism of action. These differences may alter treatment strategies that target the RAS in several pathological conditions. Recent work from our laboratory has demonstrated significant upregulation of the cardiac, intracellular RAS in diabetes, which is associated with cardiac dysfunction. Here, we have reviewed evidence supporting an intracellular RAS in different cell types, ANG II's actions in cardiac cells, and its mechanism of action, focusing on the intracellular cardiac RAS in diabetes. We have discussed the significance of an intracellular RAS in cardiac pathophysiology and implications for potential therapies.

The intracrine renin-angiotensin system.

The RAS (renin-angiotensin system) is one of the earliest and most extensively studied hormonal systems. The RAS is an atypical hormonal system in several ways. The major bioactive peptide of the system, AngII (angiotensin II), is neither synthesized in nor targets one specific organ. New research has identified additional peptides with important physiological and pathological roles. More peptides also mean newer enzymatic cascades that generate these peptides and more receptors that mediate their function. In addition, completely different roles of components that constitute the RAS have been uncovered, such as that for prorenin via the prorenin receptor. Complexity of the RAS is enhanced further by the presence of sub-systems in tissues, which act in an autocrine/paracrine manner independent of the endocrine system. The RAS seems relevant at the cellular level, wherein individual cells have a complete system, termed the intracellular RAS. Thus, from cells to tissues to the entire organism, the RAS exhibits continuity while maintaining independent control at different levels. The intracellular RAS is a relatively new concept for the RAS. The present review provides a synopsis of the literature on this system in different tissues.

Lipid rafts, caveolae and GPI-linked proteins.

Lipid rafts and caveolae are specialized membrane microdomains enriched in sphingolipids and cholesterol. They function in a variety of cellular processes including but not limited to endocytosis, transcytosis, signal transduction and receptor recycling. Here, we outline the similarities and differences between lipid rafts and caveolae as well as discuss important components and functions of each.