Which way up? Recognition of homologous DNA segments in parallel and antiparallel alignment

Homologous gene shuffling between DNA promotes genetic diversity and is an important pathway for DNA repair. For this to occur, homologous genes need to find and recognize each other. However, despite its central role in homologous recombination, the mechanism of homology recognition is still an unsolved puzzle. While specific proteins are known to play a role at later stages of recombination, an initial coarse grained recognition step has been proposed. This relies on the sequence dependence of the DNA structural parameters, such as twist and rise, mediated by intermolecular interactions, in particular electrostatic ones. In this proposed mechanism, sequences having the same base pair text, or are homologous, have lower interaction energy than those sequences with uncorrelated base pair texts; the difference termed the recognition energy. Here, we probe how the recognition energy changes when one DNA fragment slides past another, and consider, for the first time, homologous sequences in antiparallel alignment. This dependence on sliding was termed the recognition well. We find that there is recognition well for anti-parallel, homologous DNA tracts, but only a very shallow one, so that their interaction will differ little from the interaction between two nonhomologous tracts. This fact may be utilized in single molecule experiments specially targeted to test the theory. As well as this, we test previous theoretical approximations in calculating the recognition well for parallel molecules against MC simulations, and consider more rigorously the optimization of the orientations of the fragments about their long axes. The more rigorous treatment affects the recognition energy a little, when the molecules are considered rigid. However when torsional flexibility of the DNA molecules is introduced, we find excellent agreement between analytical approximation and simulation.Comment: Paper with supplemental material attached. 41 pages in all, 4 figures in main text, 3 figures in supplmental. To be submitted to Journa

QED_3 theory of underdoped high temperature superconductors II: the quantum critical point

We study the effect of gapless quasiparticles in a d-wave superconductor on the T=0 end point of the Kosterlitz-Thouless transition line in underdoped high-temperature superconductors. Starting from a lattice model that has gapless fermions coupled to 3D XY phase fluctuations of the superconducting order parameter, we propose a continuum field theory to describe the quantum phase transition between the d-wave superconductor and the spin-density-wave insulator. Without fermions the theory reduces to the standard Higgs scalar electrodynamics (HSE), which is known to have the critical point in the inverted XY universality class. Extending the renormalization group calculation for the HSE to include the coupling to fermions, we find that the qualitative effect of fermions is to increase the portion of the space of coupling constants where the transition is discontinuous. The critical exponents at the stable fixed point vary continuously with the number of fermion fields $N$, and we estimate the correlation length exponent (nu = 0.65) and the vortex field anomalous dimension(eta_Phi=-0.48) at the quantum critical point for the physical case N=2. The stable critical point in the theory disappears for the number of Dirac fermions N > N_c, with N_c ~ 3.4 in our approximation. We discuss the relationship between the superconducting and the chiral (SDW) transitions, and point to some interesting parallels between our theory and the Thirring model.Comment: 13 pages including figures in tex

On defining the Hamiltonian beyond quantum theory

Energy is a crucial concept within classical and quantum physics. An essential tool to quantify energy is the Hamiltonian. Here, we consider how to define a Hamiltonian in general probabilistic theories, a framework in which quantum theory is a special case. We list desiderata which the definition should meet. For 3-dimensional systems, we provide a fully-defined recipe which satisfies these desiderata. We discuss the higher dimensional case where some freedom of choice is left remaining. We apply the definition to example toy theories, and discuss how the quantum notion of time evolution as a phase between energy eigenstates generalises to other theories.Comment: Authors' accepted manuscript for inclusion in the Foundations of Physics topical collection on Foundational Aspects of Quantum Informatio

Critical-point scaling function for the specific heat of a Ginzburg-Landau superconductor

If the zero-field transition in high temperature superconductors such as YBa_2Cu_3O_7-\delta is a critical point in the universality class of the 3-dimensional XY model, then the general theory of critical phenomena predicts the existence of a critical region in which thermodynamic functions have a characteristic scaling form. We report the first attempt to calculate the universal scaling function associated with the specific heat, for which experimental data have become available in recent years. Scaling behaviour is extracted from a renormalization-group analysis, and the 1/N expansion is adopted as a means of approximation. The estimated scaling function is qualitatively similar to that observed experimentally, and also to the lowest-Landau-level scaling function used by some authors to provide an alternative interpretation of the same data. Unfortunately, the 1/N expansion is not sufficiently reliable at small values of N for a quantitative fit to be feasible.Comment: 20 pages; 4 figure

SARS-CoV-2 neutralizing antibodies : longevity, breadth, and evasion by emerging viral variants

The Severe Acute Respiratory Syndrome Coronavirus 2 (SAU ARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus–cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)–confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of “high responders” maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design

Systematic Improvements in Transmon Qubit Coherence Enabled by Niobium Surface Encapsulation

We present a novel transmon qubit fabrication technique that yields systematic improvements in T$_1$ coherence times. We fabricate devices using an encapsulation strategy that involves passivating the surface of niobium and thereby preventing the formation of its lossy surface oxide. By maintaining the same superconducting metal and only varying the surface structure, this comparative investigation examining different capping materials and film substrates across different qubit foundries definitively demonstrates the detrimental impact that niobium oxides have on the coherence times of superconducting qubits, compared to native oxides of tantalum, aluminum or titanium nitride. Our surface-encapsulated niobium qubit devices exhibit T$_1$ coherence times 2 to 5 times longer than baseline niobium qubit devices with native niobium oxides. When capping niobium with tantalum, we obtain median qubit lifetimes above 200 microseconds. Our comparative structural and chemical analysis suggests that amorphous niobium suboxides may induce higher losses. These results are in line with high-accuracy measurements of the niobium oxide loss tangent obtained with ultra-high Q superconducting radiofrequency (SRF) cavities. This new surface encapsulation strategy enables further reduction of dielectric losses via passivation with ambient-stable materials, while preserving fabrication and scalable manufacturability thanks to the compatibility with silicon processes

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Protein Kinase C Delta (PKCδ) Affects Proliferation of Insulin-Secreting Cells by Promoting Nuclear Extrusion of the Cell Cycle Inhibitor p21Cip1/WAF1

BACKGROUND:High fat diet-induced hyperglycemia and palmitate-stimulated apoptosis was prevented by specific inhibition of protein kinase C delta (PKCδ) in β-cells. To understand the role of PKCδ in more detail the impact of changes in PKCδ activity on proliferation and survival of insulin-secreting cells was analyzed under stress-free conditions. METHODOLOGY AND PRINCIPAL FINDINGS:Using genetic and pharmacological approaches, the effect of reduced and increased PKCδ activity on proliferation, apoptosis and cell cycle regulation of insulin secreting cells was examined. Proteins were analyzed by Western blotting and by confocal laser scanning microscopy. Increased expression of wild type PKCδ (PKCδWT) significantly stimulated proliferation of INS-1E cells with concomitant reduced expression and cytosolic retraction of the cell cycle inhibitor p21(Cip1/WAF1). This nuclear extrusion was mediated by PKCδ-dependent phosphorylation of p21(Cip1/WAF1) at Ser146. In kinase dead PKCδ (PKCδKN) overexpressing cells and after inhibition of endogenous PKCδ activity by rottlerin or RNA interference phosphorylation of p21(Cip1/WAF1) was reduced, which favored its nuclear accumulation and apoptotic cell death of INS-1E cells. Human and mouse islet cells express p21(Cip1/WAF1) with strong nuclear accumulation, while in islet cells of PKCδWT transgenic mice the inhibitor resides cytosolic. CONCLUSIONS AND SIGNIFICANCE:These observations disclose PKCδ as negative regulator of p21(Cip1/WAF1), which facilitates proliferation of insulin secreting cells under stress-free conditions and suggest that additional stress-induced changes push PKCδ into its known pro-apoptotic role