Heralding two- and four-photon path entanglement on chip

Generating quantum entanglement is not only an important scientific endeavor, but will be essential to realizing quantum-enhanced technologies, in particular, quantum-enhanced measurements with precision beyond classical limits. We investigate the heralded generation of multiphoton entanglement for quantum metrology using a reconfigurable integrated waveguide device in which projective measurement of auxiliary photons heralds the generation of path-entangled states. We use four and six-photon inputs, to analyze the heralding process of two- and four-photon NOON states-a superposition of N photons in two paths, capable of enabling phase supersensitive measurements at the Heisenberg limit. Realistic devices will include imperfections; as part of the heralded state preparation, we demonstrate phase superresolution within our chip with a state that is more robust to photon loss

Recurrences of ventricular tachycardia after stereotactic arrhythmia radioablation arise outside the treated volume: analysis of the swiss cohort

BACKGROUND AND AIMS Stereotactic arrhythmia radioablation (STAR) has been recently introduced for the management of therapy-refractory ventricular tachycardia (VT). VT recurrences have been reported after STAR but the mechanisms remain largely unknown. We analyzed recurrences in our patients after STAR. METHODS From 09.2017 to 01.2020, 20 patients (68±8y, LVEF 37±15%) suffering from refractory VT were enrolled, 16/20 with a history of at least 1 electrical storm. Before STAR, an invasive electro-anatomical mapping (Carto3) of the VT substrate was performed. A mean dose of 23±2Gy was delivered to the planning target volume (PTV). RESULTS The median ablation volume was 26 ml (range 14-115) and involved the interventricular septum in 75% of patients. During the first 6 months after STAR, VT burden decreased by 92% (median value, from 108 to 10 VT/semester). After a median follow-up of 25 months, 12/20 (60%) developed a recurrence and underwent a redo ablation. VT recurrence was located in proximity of the treated substrate in 9 cases, remote from the PTV in 3 cases and involved a larger substrate over ≥3 LV segments in 2 cases. No recurrences occurred inside the PTV. Voltage measurements showed a significant decrease in both bipolar and unipolar signal amplitude after STAR. CONCLUSION STAR is a new tool available for the treatment of VT, allowing for a significant reduction of VT burden. VT recurrences are common during follow-up, but no recurrences were observed inside the PTV. Local efficacy was supported by a significant decrease in both bipolar and unipolar signal amplitude

Engineered SH2 domains with tailored specificities and enhanced affinities for phosphoproteome analysis

Protein phosphorylation is the most abundant post-translational modification in cells. Src homology 2 (SH2) domains specifically recognize phosphorylated tyrosine (pTyr) residues to mediate signaling cascades. A conserved pocket in the SH2 domain binds the pTyr side chain and the EF and BG loops determine binding specificity. By using large phage-displayed libraries, we engineered the EF and BG loops of the Fyn SH2 domain to alter specificity. Engineered SH2 variants exhibited distinct specificity profiles and were able to bind pTyr sites on the epidermal growth factor receptor, which were not recognized by the wild-type Fyn SH2 domain. Furthermore, mass spectrometry showed that SH2 variants with additional mutations in the pTyr-binding pocket that enhanced affinity were highly effective for enrichment of diverse pTyr peptides within the human proteome. These results showed that engineering of the EF and BG loops could be used to tailor SH2 domain specificity, and SH2 variants with diverse specificities and high affinities for pTyr residues enabled more comprehensive analysis of the human phosphoproteome. Statement: Src Homology 2 (SH2) domains are modular domains that recognize phosphorylated tyrosine embedded in proteins, transducing these post-translational modifications into cellular responses. Here we used phage display to engineer hundreds of SH2 domain variants with altered binding specificities and enhanced affinities, which enabled efficient and differential enrichment of the human phosphoproteome for analysis by mass spectrometry. These engineered SH2 domain variants will be useful tools for elucidating the molecular determinants governing SH2 domains binding specificity and for enhancing analysis and understanding of the human phosphoproteome

Expression of yeast lipid phosphatase Sac1p is regulated by phosphatidylinositol-4-phosphate

<p>Abstract</p> <p>Background</p> <p>Phosphoinositides play a central role in regulating processes at intracellular membranes. In yeast, a large number of phospholipid biosynthetic enzymes use a common mechanism for transcriptional regulation. Yet, how the expression of genes encoding lipid kinases and phosphatases is regulated remains unknown.</p> <p>Results</p> <p>Here we show that the expression of lipid phosphatase Sac1p in the yeast <it>Saccharomyces cerevisiae </it>is regulated in response to changes in phosphatidylinositol-4-phosphate (PI(4)P) concentrations. Unlike genes encoding enzymes involved in phospholipid biosynthesis, expression of the <it>SAC1 </it>gene is independent of inositol levels. We identified a novel 9-bp motif within the 5' untranslated region (5'-UTR) of <it>SAC1 </it>that is responsible for PI(4)P-mediated regulation. Upregulation of <it>SAC1 </it>promoter activity correlates with elevated levels of Sac1 protein levels.</p> <p>Conclusion</p> <p>Regulation of Sac1p expression via the concentration of its major substrate PI(4)P ensures proper maintenance of compartment-specific pools of PI(4)P.</p