Coulomb entangler and entanglement testing network for waveguide qubits

We present a small network for the testing of the entanglement of two ballistic electron waveguide qubits. The network produces different output conditional on the presence or absence of entanglement. The structure of the network allows for the determination of successful entanglement operations through the measurement of the output of a single qubit. We also present a simple model of a dynamic coulomb-like interaction and use it to describe some characteristics of a proposed scheme for the entanglement of qubits in ballistic electron waveguides.Comment: 12 pages of text plus 7 figures: total 19 page

Generalized Pauli principle for particles with distinguishable traits

The s=3/2 Ising spin chain with uniform nearest-neighbor coupling, quadratic single-site potential, and magnetic field is shown to be equivalent to a system of 17 species of particles with internal structure. The same set of particles (with different energies) is shown to generate the spectrum of the s=1/2 Ising chain with dimerized nearest-neighbor coupling. The particles are free of interaction energies even at high densities. The mutual exclusion statistics of particles from all species is determined by their internal structure and encoded in a generalized Pauli principle. The exact statistical mechanical analysis can be performed for thermodynamically open or closed systems and with arbitrary energies assigned to all particle species. Special circumstances make it possible to merge two or more species into a single species. All traits that distinguish the original species become ignorable. The particles from the merged species are effectively indistinguishable and obey modified exclusion statistics. Different mergers may yield the same endproduct, implying that the inverse process (splitting any species into subspecies) is not unique. In a macroscopic system of two merged species at thermal equilibrium, the concentrations of the original species satisfy a functional relation governed by their mutual statistical interaction. That relation is derivable from an extremum principle. In the Ising context the system is open and the particle energies depend on the Hamiltonian parameters. Simple models of polymerization and solitonic paramagnetism each represent a closed system of two species that can transform into each other. Here they represent distinguishable traits with different energies of the same physical particle.Comment: 12 pages, 7 figures, 6 table

Pseudo-affinity purification and formulation of a cell-culture derived whole influenza virus vaccine using magnetic sulfated cellulose particles

The production of viral vaccines usually employs different unit operations where formulation and filling are the final steps of downstream processing (DSP). However, complex DSP is often hard to realize in research laboratories focusing on novel vaccine candidates. Moreover, there are no real ready-to-use tools for high-throughput DSP of whole virus particles that can speed up development. Because of these needs we developed a new platform for easy and straightforward whole virus particle purification and formulation based on magnetic sulfated cellulose particles (MSCP)1,2. Proof of concept was carried out with an influenza A/Puerto Rico/8/34 (H1N1) whole virus vaccine for the immunization of mice. The virus particles were produced in suspension MDCK cells, clarified, inactivated, and concentrated using a standard protocol. After diafiltration to low salt buffer, the virus particles were bound to the MSCP and the virus loaded MSCP were washed and resuspended in formulation buffer. Please click Additional Files below to see the full abstract

Purification of cell culture-derived influenza virus via continuous chromatography

In vaccine production downstream processing often constitutes a bottleneck in terms of process productivity and economy. One way to design more efficient purification trains could be the implementation of continuous chromatographic methods. The aim of this study was the purification of cell culture-derived influenza virus using continuous chromatography. Therefore, two chromatographic modes, flow through with CaptoCore (CC) beads and bind and elute with anion exchange (AEX) monoliths, were characterized for their ability to separate the virus from contaminating host cell protein and DNA. The starting material for the CC was treated with nuclease to decrease the DNA content and fragment size. Further, regeneration conditions for the chromatographic media, a prerequisite for successful continuous implementation, were identified and verified in sequential batch experiments. Simulated moving bed chromatography (SMB) was performed in an open loop configuration using constant switching times. In case of the CC material, two columns were located in the separation zones and two additional columns were regenerated and equilibrated in detached zones. For the AEX runs, on the other hand, monoliths were used in a three zone configuration with detached high salt zone for regeneration. Results in batch chromatography (BC) and SMB showed similar product yields in the range 60 to 100%. Contaminant depletion was \u3e98% DNA and \u3e58% protein for the AEX monoliths. Both the CC SMB and the BC resulted in comparable impurity levels (33.2 µg protein and 25.6 ng DNA per estimated 15 µg HA) but for BC a higher product yield (89% vs 72%) was achieved. In addition, the virus dilution during the flow through chromatography could be reduced in the cyclic steady state of the SMB by a factor of 1.8. Overall, the separation performance of the BC has been successfully transferred to the continuous process

Altered Resting-State Networks in Adolescent Non-Suicidal Self-Injury – A Graph Theory Analysis

Non-suicidal self-injury (NSSI) is a highly prevalent transdiagnostic symptom and risk marker for mental health problems among adolescents. Research on the neurobiological mechanisms underlying NSSI is needed to clarify the neural correlates associated with the behavior. We examined resting-state-functional-connectivity (RSFC) in n = 33 female adolescents aged 12-17 years engaging in NSSI, and n = 29 age-matched healthy controls using graph theory. Mixed linear models were evaluated with the Bayes Factor (BF) to determine group differences on global and regional network measures and associations between network measures and clinical characteristics in patients. Adolescents engaging in NSSI demonstrated longer average characteristic path lengths and a smaller number of weighted hubs globally. Regional measures indicated lower efficiency and worse integration in (orbito)frontal regions and higher weighted coreness in the pericalcarine gyrus. In patients, higher orbitofrontal weighted local efficiency was associated with NSSI during the past month while lower pericalcarine nodal efficiency was associated with suicidal thoughts in the past year. Higher right but lower left pericalcarine weighted hubness was associated with more suicide attempts during the past year. Using a graph-based technique to identify functional connectivity networks, this study adds to the growing understanding of the neurobiology of NSSI

Differential outcomes of outpatient only versus combined inpatient/outpatient treatment in early intervention for adolescent borderline personality disorder.

Clinical guidelines for adults with borderline personality disorder (BPD) recommend outpatient psychotherapy as first-line treatment. Little is known whether this recommendation is also applicable to adolescents. The current study examined the relationship between treatment setting and the outcome of early intervention for adolescents with BPD pathology. One-hundred and seventy-eight adolescents from a specialized outpatient clinic were assessed at baseline, and at 1- and 2-year follow-up. Sixty-three participants who received inpatient treatment during the first year were assigned to the "combined inpatient/outpatient group", 115 participants to the "outpatient only group". Generalized linear and mixed models with inverted probability weights to adjust for baseline differences were applied to examine the impact of group on clinical changes over time. Both groups demonstrated a significant decrease in BPD features, depressive symptoms, psychopathological distress, non-suicidal self-injury (NSSI), suicidal thoughts, suicide attempts, and overall illness severity, and a significant increase in quality of life and psychosocial functioning from baseline to follow-up 2. The decrease in NSSI and overall illness severity, and the increase in psychosocial functioning from baseline to follow-up 1 were greater in the outpatient only group, with comparable improvements between groups from follow-up 1 to follow-up 2. Both outpatient treatment and combined outpatient/inpatient treatment resulted in clinical improvements over time, with some indication for faster changes in the outpatient only setting. The findings provide preliminary evidence that the recommendation of outpatient psychotherapy as the first-line treatment for BPD also holds true for adolescents

Continuous purification of cell culture-derived influenza A virus particles through pseudo- affinity membrane chromatography

Continuous manufacturing is a relevant trend in biopharmaceutical production to reduce the process footprint and to improve the process economy. Vaccines against world-spread diseases, such as influenza, should benefit in particular from such an approach, given the increasing demand for seasonal vaccines and the need for a fast response in case of a pandemic outbreak. Upstream processing of viral vaccines has seen important progress in continuous production of viral vaccines [1], which further supports the development of hybrid or fully continuous flow-schemes for downstream processing. Please click Additional Files below to see the full abstract

A capacitance spectroscopy-based platform for realizing gate-defined electronic lattices

Electrostatic confinement in semiconductors provides a flexible platform for the emulation of interacting electrons in a two-dimensional lattice, including in the presence of gauge fields. This combination offers the potential to realize a wide host of quantum phases. Here we present a measurement and fabrication scheme that builds on capacitance spectroscopy and allows for the independent control of density and periodic potential strength imposed on a two-dimensional electron gas. We characterize disorder levels and (in)homogeneity and develop and optimize different gating strategies at length scales where interactions are expected to be strong. A continuation of these ideas might see to fruition the emulation of interaction-driven Mott transitions or Hofstadter butterfly physics

Purifying viruses with a sheet of paper: Single-use steric exclusion chromatography as a capture platform for vaccine candidates

Steric exclusion chromatography (SXC) is a method in which a crude sample is mixed with polyethylene glycol (PEG) and fed to a hydrophilic stationary phase. Selectivity in SXC is strongly influenced by the target species’ size, so it is particularly well suited for purification of large biomolecules such as viruses and virus-like-particles. The product is captured without a direct chemical interaction thanks to the mutual steric exclusion of PEG between the product and the stationary phase (cellulose membranes with micron-sized pores). Product elution is achieved by removing the PEG from solution, and can theoretically be made in any buffer system. The low cost of the cellulose membranes allows this operation to be single-use. Using SXC, we have achieved virtually full recovery of several viruses produced in serum-free mammalian cell culture: influenza virus, yellow fever virus, and Modified Vaccinia Ankara (MVA) virus. For influenza virus, four different strains were produced separately in MDCK cell suspension cultures using either chemically defined medium or serum-free medium. Full recovery of all strains was observed using identical SXC conditions (loading with 8% PEG-6000) for both infectious and chemically inactivated virus particles. Coupling a nuclease treatment for DNA digestion prior to SXC, dsDNA was depleted \u3e99.98%. The column capacity in terms of the viral hemagglutinin antigen was at least 50 mg m−2. In the case of yellow fever virus, two attenuated strains used for commercial manufacture were produced separately in adherent Vero cells grown in serum-free medium. Full recovery of infective virus titer for both strains was attained using 10% PEG-6000 for sample load. The elution fraction was concentrated \u3e100-fold compared to the feed with the very high titer of 6×109 plaque forming units, equivalent to ≈100 000 doses. Total recovery was also observed for MVA virus loaded at 4% PEG-6000; produced in an avian cell line in chemically defined medium, the SXC elution pools contained ≈3.7×109 virions as estimated by TCID50 assay. In conclusion, SXC can drastically reduce process development in terms of time and equipment requirements. The convenience of purifying different virus strains using similar chromatography conditions is almost impossible to match by other methods, as are the high product recoveries typically achieved with SXC. The latter gives space to include additional polishing operations without risking low overall process yields. We deem membrane-based SXC as a promising platform technology for capturing viruses and virus-like particles in vaccine manufacturing