Witnessing eigenstates for quantum simulation of Hamiltonian spectra

The efficient calculation of Hamiltonian spectra, a problem often intractable on classical machines, can find application in many fields, from physics to chemistry. Here, we introduce the concept of an "eigenstate witness" and through it provide a new quantum approach which combines variational methods and phase estimation to approximate eigenvalues for both ground and excited states. This protocol is experimentally verified on a programmable silicon quantum photonic chip, a mass-manufacturable platform, which embeds entangled state generation, arbitrary controlled-unitary operations, and projective measurements. Both ground and excited states are experimentally found with fidelities >99%, and their eigenvalues are estimated with 32-bits of precision. We also investigate and discuss the scalability of the approach and study its performance through numerical simulations of more complex Hamiltonians. This result shows promising progress towards quantum chemistry on quantum computers.Comment: 9 pages, 4 figures, plus Supplementary Material [New version with minor typos corrected.

Semiclassical transmission across transition states

It is shown that the probability of quantum-mechanical transmission across a phase space bottleneck can be compactly approximated using an operator derived from a complex Poincar\'e return map. This result uniformly incorporates tunnelling effects with classically-allowed transmission and generalises a result previously derived for a classically small region of phase space.Comment: To appear in Nonlinearit

The Microbiome in Bronchial Biopsies from Smokers and Ex-Smokers with Stable COPD - A Metatranscriptomic Approach

Current knowledge about the respiratory microbiome is mainly based on 16S ribosomal RNA gene sequencing. Newer sequencing approaches, such as metatranscriptomics, offer the technical ability to measure the viable microbiome response to environmental conditions such as smoking as well as to explore its functional role by investigating host-microbiome interactions. However, knowledge about its feasibility in respiratory microbiome research, especially in lung biopsies, is still very limited. RNA sequencing was performed in bronchial biopsies from clinically stable smokers (n=5) and ex-smokers (n=6) with COPD not using (inhaled) steroids. The Trinity assembler was used to assemble non-human reads in order to allow unbiased taxonomical and microbial transcriptional analyses. Subsequently, host-microbiome interactions were analyzed based on associations with host transcriptomic data. Ultra-low levels of microbial mass (0.009%) were identified in the RNA-seq data. Overall, no differences were identified in microbiome diversity or transcriptional profiles of microbial communities or individual microbes between COPD smokers and ex-smokers in the initial test dataset as well as a larger replication dataset. We identified an upregulated host gene set, related to the simultaneous presence of Bradyrhizobium, Roseomonas, Brevibacterium.spp., which were related to PERK-mediated unfolded protein response (UPR) and expression of the microRNA-155-5p. Our results show that metatranscriptomic profiling in bronchial biopsy samples from stable COPD patients yields ultra-low levels of microbial mass. Further, this study illustrates the potential of using transcriptional profiling of the host and microbiome to gain more insight into their interaction in the airways

Systematic evaluation of an atomic clock at 2e-18 total uncertainty

The pursuit of better atomic clocks has advanced many research areas, providing better quantum state control, new insights in quantum science, tighter limits on fundamental constant variation, and improved tests of relativity. The record for the best stability and accuracy is currently held by optical lattice clocks. This work takes an important step towards realizing the full potential of a many-particle clock with a state-of-the-art stable laser. Our 87Sr optical lattice clock now achieves fractional stability of 2.2e-16 at 1 s. With this improved stability, we perform a new accuracy evaluation of our clock, reducing many systematic uncertainties that limited our previous measurements, such as those in the lattice ac Stark shift, the atoms' thermal environment, and the atomic response to room-temperature BBR. Our combined measurements have reduced the total uncertainty of the JILA Sr clock to 2.1e-18 in fractional frequency units.Comment: Full published versio

Relative Pitch Perception and the Detection of Deviant Tone Patterns.

Most people are able to recognise familiar tunes even when played in a different key. It is assumed that this depends on a general capacity for relative pitch perception; the ability to recognise the pattern of inter-note intervals that characterises the tune. However, when healthy adults are required to detect rare deviant melodic patterns in a sequence of randomly transposed standard patterns they perform close to chance. Musically experienced participants perform better than naïve participants, but even they find the task difficult, despite the fact that musical education includes training in interval recognition.To understand the source of this difficulty we designed an experiment to explore the relative influence of the size of within-pattern intervals and between-pattern transpositions on detecting deviant melodic patterns. We found that task difficulty increases when patterns contain large intervals (5-7 semitones) rather than small intervals (1-3 semitones). While task difficulty increases substantially when transpositions are introduced, the effect of transposition size (large vs small) is weaker. Increasing the range of permissible intervals to be used also makes the task more difficult. Furthermore, providing an initial exact repetition followed by subsequent transpositions does not improve performance. Although musical training correlates with task performance, we find no evidence that violations to musical intervals important in Western music (i.e. the perfect fifth or fourth) are more easily detected. In summary, relative pitch perception does not appear to be conducive to simple explanations based exclusively on invariant physical ratios

Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina

Background: Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity. Methods/Design: Sixty patients with stable angina will be recruited and randomised 1: 1 to exercise training or conventional care. Patients randomised to exercise training will attend an exercise physiology laboratory up to three times weekly for supervised aerobic interval training sessions of one hour in total duration. Patients will undergo assessments of angina, anxiety, depression, and peripheral blood gene expression at baseline, after six and twelve weeks of training, and twelve weeks after formal exercise training ceases. Discussion: This study will provide comprehensive data on the effect of exercise training on peripheral blood gene expression in patients with angina. By correlating this with improvement in angina status we will identify candidate peripheral blood transcriptional markers predictive of improvements in angina level in response to exercise training

Randomized phase II trial of bevacizumab plus everolimus versus bevacizumab alone for recurrent or persistent ovarian, fallopian tube or peritoneal carcinoma: An NRG oncology/gynecologic oncology group study

PURPOSE: Bevacizumab (BV) monotherapy leads to compensatory upregulation of multiple signaling pathways, resulting in mTOR activation. We evaluated combining BV and everolimus (EV), an mTOR kinase inhibitor, to circumvent BV-resistance in women with recurrent or persistent ovarian, fallopian tube or primary peritoneal cancer (OC). PATIENTS AND METHODS: Eligible OC patients had measurable (RECIST1.1) or detectable disease, 1-3 prior regimens, performance status (PS) 0-2, and no prior m-TOR inhibitor. All patients received BV 10 mg/kg IV every 2wks. Patients were randomized (1:1) to oral EV (10 mg daily) or placebo stratified by platinum-free interval (PFI), measurable disease and prior BV. Primary endpoint was progression-free survival (PFS); secondary endpoints included safety and response. RESULTS: 150 patients were randomized to BV with (n = 75) and without (n = 75) EV. Arms were well-balanced for age (median 63: range 28-92), PS (0: 73%, 1-2: 27%), prior regimens (1: 37%, 2: 47%, 3: 16%), prior BV (11%), PFI (<6mos: 65%) and measurable disease (81%). The BV + EV vs BV median PFS was 5.9 vs 4.5 months (hazard ratio [HR] 0.95 (95% CI, 0.66-1.37, p = 0.39)). Median OS was 16.6 vs 17.3 months (HR 1.16 (95% CI, 0.72-1.87, p = 0.55). Objective measurable responses were higher with BV + EV (22% vs 12%). Study removal due to toxicity was higher with BV + EV (29% vs 12%). Toxicity (≥grade 3) from BV + EV were "other GI (mucositis)" (23 vs 1%) and "metabolic/nutrition" (19 vs. 7%); common ≥ grade 2 toxicities with BV + EV were cytopenia, nausea, fatigue and rash. CONCLUSION: The combination regimen (BV + EV) did not significantly reduce the hazard of progression or death relative to BV and was associated with higher rates of adverse events and study discontinuation when compared to BV alone

Effects of supervised exercise training on lower-limb cutaneous microvascular reactivity in adults with venous ulcers

Purpose: To investigate the effects of a 12-week supervised exercise programme on lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration. Methods: Thirty-eight adults with unilateral venous ulceration who were being treated with lower-limb compression therapy (58% male; mean age 65 years; median ulcer size 5 cm2) were randomly allocated to exercise or control groups. Exercise participants (n=18) were invited to attend thrice weekly sessions of lower-limb aerobic and resistance exercise for 12 weeks. Cutaneous microvascular reactivity was assessed in the gaiter region of ulcerated and non-ulcerated legs at baseline and 3 months using laser Doppler fluxmetry coupled with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Cutaneous vascular conductance (CVC) was calculated as laser Doppler flux (AU)/mean arterial pressure (mmHg). Results: Thirty-seven participants completed follow-up assessments. Median class attendance was 36 (range 2 to 36). Analyses of covariance revealed greater peak CVC responses to ACh in the exercise group at 3 months in both the ulcerated (adjusted difference = 0.944 AU/mmHg; 95% CI 0.504 to 1.384) and non-ulcerated (adjusted difference = 0.596 AU/mmHg; 95% CI 0.028 to 1.164) legs. Peak CVC responses to SNP were also greater in the exercise group at 3 months in the ulcerated leg (adjusted difference = 0.882 AU/mmHg; 95% CI 0.274 to 1.491), but not the non-ulcerated leg (adjusted difference = 0.392 AU/mmHg; 95% CI -0.377 to 1.161). Conclusion: Supervised exercise training improves lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration. Keywords Randomized controlled trial; Exercise; Ulceration; Vascular function; Laser Doppler fluxmetry; Iontophoresi

Immunohistochemical, morphological and ultrastructural resemblance between dendritic cells and folliculo-stellate cells in normal human and rat anterior pituitaries

Immunolabeling of cryo-sections of human anterior pituitaries obtained at autopsy, and of cryo-sections of freshly prepared rat anterior pituitaries, with a panel of monoclonal antibodies against markers of the monocyte/dendritic cell/macrophage lineage, reveals in both species a characteristic pattern of immunopositive cells, among which many cells with dendritic phenotype are found. Cells characterized by marker expression of MHC-class II determinants and a dendritic morphology are present in both human and rat anterior pituitary. Markers characteristic of dendritic cells such as the L25 antigen and the OX62 antigen were present in anterior pituitaries from human and rat respectively. The population of MHC-class II expressing dendritic cells of the rat anterior pituitary is compared at the ultrastructural level with the folliculo-stellate cell population, which cell type has been previously characterized by its distinctive ultrastructure and immunopositivity for the S100 protein. Using immune-electron microscopy of rat anterior pituitaries fixed with periodate-lysine-paraformaldehyde, we were able to distinguish non-granulated cells expressing MHC-class II determinants, whereas no MHC-class II expression was found in the granulated endocrine cells. Using double immunolabeling of cryo-sections of these rat AP with 25 nm and 15 nm gold labels, we demonstrated an overlap between the populations of MHC-class II-expressing and S100 protein-expressing cells. Furthermore, MHC-class II-expressing and S100-positive cells showed ultrastructural characteristics that have been previously ascribed to folliculo-stellate cells. At the light microscopical level in the rat AP, a proportion of 10 to 20% of the S100-positive cells was found immunopositive for the MHC-class II marker OX6. In the hu

Differential sensing with arrays of de novo designed peptide assemblies

Differential sensing attempts to mimic the mammalian senses of smell and taste to identify analytes and complex mixtures. In place of hundreds of complex, membrane-bound G-protein coupled receptors, differential sensors employ arrays of small molecules. Here we show that arrays of computationally designed de novo peptides provide alternative synthetic receptors for differential sensing. We use self-assembling α-helical barrels (αHBs) with central channels that can be altered predictably to vary their sizes, shapes and chemistries. The channels accommodate environment-sensitive dyes that fluoresce upon binding. Challenging arrays of dye-loaded barrels with analytes causes differential fluorophore displacement. The resulting fluorimetric fingerprints are used to train machine-learning models that relate the patterns to the analytes. We show that this system discriminates between a range of biomolecules, drink, and diagnostically relevant biological samples. As αHBs are robust and chemically diverse, the system has potential to sense many analytes in various settings