Transcriptional reprogramming in yeast using dCas9 and combinatorial gRNA strategies

Additional file 3: Figure S2. Time-dependent regulation of reporter gene expression. Data were obtained with a BioLector from the same cultures as used in Supplementary Fig. S1. Indicated strains were targeted at pHMG1 or pOLE1 as in Fig. 1C with controls (ctrl) expressing dCas9 and no gRNA. Data were collected for ~47 hrs and are presented as the average of three biological replicates. A. MFI from strains targeted with the constitutive system is presented per DCW/L (dry cell weight per liter) as a function of time. Blue; control. Green; activation (MCP-VPR). Red; repression (PCP-Mxi1). B. MFI from cultures added 250 ng/mL aTc to activate the inducible system is presented per OD (OD600) over time. Blue; control. Green; activation (dCas9-VPR). Red; repression (dCas9-Mxi1)

Lattice dynamics reveals a local symmetry breaking in the emergent dipole phase of PbTe

Local symmetry breaking in complex materials is emerging as an important contributor to materials properties but is inherently difficult to study. Here we follow up an earlier structural observation of such a local symmetry broken phase in the technologically important compound PbTe with a study of the lattice dynamics using inelastic neutron scattering (INS). We show that the lattice dynamics are responsive to the local symmetry broken phase, giving key insights in the behavior of PbTe, but also revealing INS as a powerful tool for studying local structure. The new result is the observation of the unexpected appearance on warming of a new zone center phonon branch in PbTe. In a harmonic solid the number of phonon branches is strictly determined by the contents and symmetry of the unit cell. The appearance of the new mode indicates a crossover to a dynamic lower symmetry structure with increasing temperature. No structural transition is seen crystallographically but the appearance of the new mode in inelastic neutron scattering coincides with the observation of local Pb off-centering dipoles observed in the local structure. The observation resembles relaxor ferroelectricity but since there are no inhomogeneous dopants in pure PbTe this anomalous behavior is an intrinsic response of the system. We call such an appearance of dipoles out of a non-dipolar ground-state "emphanisis" meaning the appearance out of nothing. It cannot be explained within the framework of conventional phase transition theories such as soft-mode theory and challenges our basic understanding of the physics of materials

Coulomb interaction-driven entanglement of electrons on helium

The generation and evolution of entanglement in quantum many-body systems is an active area of research that spans multiple fields, from quantum information science to the simulation of quantum many-body systems encountered in condensed matter, subatomic physics, and quantum chemistry. Motivated by recent experiments exploring quantum information processing systems with electrons trapped above the surface of cryogenic noble gas substrates, we theoretically investigate the generation of \emph{motional} entanglement between two electrons via their unscreened Coulomb interaction. The model system consists of two electrons confined in separate electrostatic traps which establish microwave frequency quantized states of their motion. We compute the motional energy spectra of the electrons, as well as their entanglement, by diagonalizing the model Hamiltonian with respect to a single-particle Hartree product basis. This computational procedure can in turn be employed for device design and guidance of experimental implementations. In particular, the theoretical tools developed here can be used for fine tuning and optimization of control parameters in future experiments with electrons trapped above the surface of superfluid helium or solid neon.Comment: Revised figures and discussion

Flu Vaccine and Mortality in Hypertension:A Nationwide Cohort Study

BACKGROUND: Influenza infection may increase the risk of stroke and acute myocardial infarction (AMI). Whether influenza vaccination may reduce mortality in patients with hypertension is currently unknown. METHODS AND RESULTS: We performed a nationwide cohort study including all patients with hypertension in Denmark during 9 consecutive influenza seasons in the period 2007 to 2016 who were prescribed at least 2 different classes of antihypertensive medication (renin‐angiotensin system inhibitors, diuretics, calcium antagonists, or beta‐blockers). We excluded patients who were aged 100 years, had ischemic heart disease, heart failure, chronic obstructive lung disease, cancer, or cerebrovascular disease. The exposure to influenza vaccination was assessed before each influenza season. The end points were defined as death from all‐causes, from cardiovascular causes, or from stroke or AMI. For each influenza season, patients were followed from December 1 until April 1 the next year. We included a total of 608 452 patients. The median follow‐up was 5 seasons (interquartile range, 2–8 seasons) resulting in a total follow‐up time of 975 902 person‐years. Vaccine coverage ranged from 26% to 36% during the study seasons. During follow‐up 21 571 patients died of all‐causes (3.5%), 12 270 patients died of cardiovascular causes (2.0%), and 3846 patients died of AMI/stroke (0.6%). After adjusting for confounders, vaccination was significantly associated with reduced risks of all‐cause death (HR, 0.82; P<0.001), cardiovascular death (HR, 0.84; P<0.001), and death from AMI/stroke (HR, 0.90; P=0.017). CONCLUSIONS: Influenza vaccination was significantly associated with reduced risks of death from all‐causes, cardiovascular causes, and AMI/stroke in patients with hypertension. Influenza vaccination might improve outcome in hypertension

Constraints on String Cosmology

String theory contains sources like orientifold planes that support higher derivative interactions. These interactions make possible static flux compactifications which are forbidden in supergravity. They can also lead to violations of the strong energy condition (SEC) which is needed for an accelerating universe. We examine how large a violation is possible in the context of the heterotic string compactified to four dimensions. We find that de Sitter solutions are still not possible but that classically forbidden anti-de Sitter solutions are possible.Comment: 22 pages; LaTeX; LaTeX issue fixed; references and a few comments added; typo in Appendix fixe

Duration of clopidogrel treatment and risk of mortality and recurrent myocardial infarction among 11 680 patients with myocardial infarction treated with percutaneous coronary intervention: a cohort study

<p>Abstract</p> <p>Background</p> <p>The optimal duration of clopidogrel treatment after percutaneous coronary intervention (PCI) is unclear. We studied the risk of death or recurrent myocardial infarction (MI) in relation to 6- and 12-months clopidogrel treatment among MI patients treated with PCI.</p> <p>Methods</p> <p>Using nationwide registers of hospitalizations and drug dispensing from pharmacies we identified 11 680 patients admitted with MI, treated with PCI and clopidogrel. Clopidogrel treatment was categorized in a 6-months and a 12-months regimen. Rates of death, recurrent MI or a combination of both were analyzed by the Kaplan Meier method and Cox proportional hazards models. Bleedings were compared between treatment regimens.</p> <p>Results</p> <p>The Kaplan Meier analysis indicated no benefit of the 12-months regimen compared with the 6-months in all endpoints. The Cox proportional hazards analysis confirmed these findings with hazard ratios for the 12-months regimen (the 6-months regimen used as reference) for the composite endpoint of 1.01 (confidence intervals 0.81-1.26) and 1.24 (confidence intervals 0.95-1.62) for Day 0-179 and Day 180-540 after discharge. Bleedings occurred in 3.5% and 4.1% of the patients in the 6-months and 12-months regimen (p = 0.06).</p> <p>Conclusions</p> <p>We found comparable rates of death and recurrent MI in patients treated with 6- and 12-months' clopidogrel. The potential benefit of prolonged clopidogrel treatment in a real-life setting remains uncertain.</p

Novel variation and <i>de novo </i>mutation rates in population-wide <i>de novo</i> assembled Danish trios

Building a population-specific catalogue of single nucleotide variants (SNVs), indels and structural variants (SVs) with frequencies, termed a national pan-genome, is critical for further advancing clinical and public health genetics in large cohorts. Here we report a Danish pan-genome obtained from sequencing 10 trios to high depth (50 × ). We report 536k novel SNVs and 283k novel short indels from mapping approaches and develop a population-wide de novo assembly approach to identify 132k novel indels larger than 10 nucleotides with low false discovery rates. We identify a higher proportion of indels and SVs than previous efforts showing the merits of high coverage and de novo assembly approaches. In addition, we use trio information to identify de novo mutations and use a probabilistic method to provide direct estimates of 1.27e−8 and 1.5e−9 per nucleotide per generation for SNVs and indels, respectively