An Open-System Quantum Simulator with Trapped Ions

The control of quantum systems is of fundamental scientific interest and promises powerful applications and technologies. Impressive progress has been achieved in isolating the systems from the environment and coherently controlling their dynamics, as demonstrated by the creation and manipulation of entanglement in various physical systems. However, for open quantum systems, engineering the dynamics of many particles by a controlled coupling to an environment remains largely unexplored. Here we report the first realization of a toolbox for simulating an open quantum system with up to five qubits. Using a quantum computing architecture with trapped ions, we combine multi-qubit gates with optical pumping to implement coherent operations and dissipative processes. We illustrate this engineering by the dissipative preparation of entangled states, the simulation of coherent many-body spin interactions and the quantum non-demolition measurement of multi-qubit observables. By adding controlled dissipation to coherent operations, this work offers novel prospects for open-system quantum simulation and computation.Comment: Pre-review submission to Nature. For an updated and final version see publication. Manuscript + Supplementary Informatio

Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface

Lysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the extracellular matrix. LOX overexpression is associated with poor cancer outcomes. Here, we find that LOX regulates the epidermal growth factor receptor (EGFR) to drive tumour progression. We show that LOX regulates EGFR by suppressing TGFβ1 signalling through the secreted protease HTRA1. This increases the expression of Matrilin2 (MATN2), an EGF-like domain-containing protein that traps EGFR at the cell surface to facilitate its activation by EGF. We describe a pharmacological inhibitor of LOX, CCT365623, which disrupts EGFR cell surface retention and delays the growth of primary and metastatic tumour cells in vivo. Thus, we show that LOX regulates EGFR cell surface retention to drive tumour progression, and we validate the therapeutic potential of inhibiting this pathway with the small molecule inhibitor CCT365623

IFNβ Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury.

Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects. We find in vivo that IFNβ mRNA is significantly increased in HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week intranasal IFNβ treatment of HIVgp120tg mice starting at 3.5 months of age increases expression of CCL4 and concomitantly protects neuronal dendrites and pre-synaptic terminals in cortex and hippocampus from gp120-induced damage. Moreover, in vivo and in vitro data suggests astrocytes are a major source of IFNβ-induced CCL4. Altogether, our results suggest exogenous IFNβ as a neuroprotective factor that has potential to ameliorate in vivo HIVgp120-induced brain injury

New MACRO results on atmospheric neutrino oscillations

The final results of the MACRO experiment on atmospheric neutrino oscillations are presented and discussed. The data concern different event topologies with average neutrino energies of ~3 and ~50 GeV. Multiple Coulomb Scattering of the high energy muons in absorbers was used to estimate the neutrino energy of each event. The angular distributions, the L/E_nu distribution, the particle ratios and the absolute fluxes all favour nu_mu --> nu_tau oscillations with maximal mixing and Delta m^2 =0.0023 eV^2. A discussion is made on the Monte Carlos used for the atmospheric neutrino flux. Some results on neutrino astrophysics are also briefly discussed.Comment: Invited Paper at the NANP03 Int. Conf., Dubna, 200

The impact of open versus closed format ICU admission practices on the outcome of high risk surgical patients: a cohort analysis

<p>Abstract</p> <p>Background</p> <p>In the year 2000, the organizational structure of the ICU in the Zaandam Medical Centre (ZMC) changed from an open to a closed format ICU. The objective of this study was to evaluate the effect of this organizational change on outcome in high risk surgical patients.</p> <p>Methods</p> <p>The medical records of all consecutive high risk surgical patients admitted to the ICU from 1996 to 1998 (open format) and from 2003 to 2005 (closed format), were reviewed. High-risk patients were defined according to the Identification of Risk in Surgical patients (IRIS) score. Parameters studied were: mortality, morbidity, ICU length of stay (LOS) and hospital LOS.</p> <p>Results</p> <p>Mortality of ICU patients was 25.7% in the open format group and 15.8% in the closed format group (p = 0.01). Morbidity decreased from 48.6% to 46.1% (p = 0.6). The average length of hospital stay was 17 days in the open format group, and 21 days in the closed format group (p = 0.03).</p> <p>Conclusions</p> <p>High risk surgical patients in the ICU are patients that have undergone complex and often extensive surgery. These patients are in need of specialized treatment and careful monitoring for maximum safety and optimal care. Our results suggest that closed format is a more favourable setting than open format to minimize the effects of high risk surgery, and to warrant safe outcome in this patient group.</p

Scaling up integration: development and results of a participatory assessment of HIV/TB services, South Africa

<p>Abstract</p> <p>Background</p> <p>In South Africa the need to integrate HIV, TB and STI programmes has been recognised at a policy and organisation level; the challenge is now one of translating policies into relevant actions and monitoring implementation to ensure that the anticipated benefits of integration are achieved. In this research, set in public primary care services in Cape Town, South Africa, we set out to determine how middle level managers could be empowered to monitor the implementation of an effective, integrated HIV/TB/STI service.</p> <p>Methods</p> <p>A team of managers and researchers designed an evaluation tool to measure implementation of key components of an integrated HIV/TB/STI package with a focus on integration. They used a comprehensive health systems framework based on conditions for programme effectiveness and then identified and collected tracer indicators. The tool was extensively piloted in two rounds involving 49 clinics in 2003 and 2004 to identify data necessary for effective facility-level management. A subsequent evaluation of 16 clinics (2 per health sub district, 12% of all public primary care facilities) was done in February 2006.</p> <p>Results</p> <p>16 clinics were reviewed and 635 records sampled. Client access to HIV/TB/STI programmes was limited in that 50% of facilities routinely deferred clients. Whilst the physical infrastructure and staff were available, there was problem with capacity in that there was insufficient staff training (for example, only 40% of clinical staff trained in HIV care). Weaknesses were identified in quality of care (for example, only 57% of HIV clients were staged in accordance with protocols) and continuity of care (for example, only 24% of VCT clients diagnosed with HIV were followed up for medical assessment). Facility and programme managers felt that the evaluation tool generated information that was useful to manage the programmes at facility and district level. On the basis of the results facility managers drew up action plans to address three areas of weakness within their own facility.</p> <p>Conclusions</p> <p>This use of the tool which is designed to empower programme and facility managers demonstrates how engaging middle managers is crucial in translating policies into relevant actions.</p

A Powerful Test of Parent-of-Origin Effects for Quantitative Traits Using Haplotypes

Imprinting is an epigenetic phenomenon where the same alleles have unequal transcriptions and thus contribute differently to a trait depending on their parent of origin. This mechanism has been found to affect a variety of human disorders. Although various methods for testing parent-of-origin effects have been proposed in linkage analysis settings, only a few are available for association analysis and they are usually restricted to small families and particular study designs. In this study, we develop a powerful maximum likelihood test to evaluate the parent-of-origin effects of SNPs on quantitative phenotypes in general family studies. Our method incorporates haplotype distribution to take advantage of inter-marker LD information in genome-wide association studies (GWAS). Our method also accommodates missing genotypes that often occur in genetic studies. Our simulation studies with various minor allele frequencies, LD structures, family sizes, and missing schemes have uniformly shown that using the new method significantly improves the power of detecting imprinted genes compared with the method using the SNP at the testing locus only. Our simulations suggest that the most efficient strategy to investigate parent-of-origin effects is to recruit one parent and as many offspring as possible under practical constraints. As a demonstration, we applied our method to a dataset from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) to test the parent-of-origin effects of the SNPs within the PPARGC1A, MTP and FABP2 genes on diabetes-related phenotypes, and found that several SNPs in the MTP gene show parent-of-origin effects on insulin and glucose levels