Quasiparticle operators with non-Abelian braiding statistics

We study the gauge invariant fermions in the fermion coset representation of $SU(N)_k$ Wess-Zumino-Witten models which create, by construction, the physical excitations (quasiparticles) of the theory. We show that they provide an explicit holomorphic factorization of $SU(N)_k$ Wess-Zumino-Witten primaries and satisfy non-Abelian braiding relations.Comment: 13 pages, no figures, final version to appear in Physics Letters

Interchangeability of Biosimilars: What Level of Clinical Evidence is Needed to Support the Interchangeability Designation in the United States

A biosimilar is a biologic drug that is highly similar to a reference (originator) product, with no clinically meaningful differences between the two products in safety, purity, and potency . Regulatory approval of a biosimilar is based on analytical, structural, and functional comparisons with the reference product, comparative nonclinical (in vivo) studies, clinical pharmacokinetics and/or pharmacodynamics, and immunogenicity. In addition, comparative clinical efficacy and safety assessments are usually conducted and, taken together, comprise the totality of the evidence supporting biosimilarity. For a biosimilar to meet the additional designation of interchangeability in the United States (US), the applicant must demonstrate that the biological drug can be expected to produce the same clinical result as the reference product in any given patient and if the biological drug is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biological drug and the reference product is no greater than the risk of using the reference product without such alternation or switch . The challenges faced in conducting clinical studies to support a designation of interchangeability, as defined in the final interchangeability guidance from the US Food and Drug Administration, are considered. Potential alternative approaches to generating adequate and sufficient clinical data to support a designation of interchangeability are also presented

Opportunities for isoporous membranes in the manufacture of genomic medicines

Viral and non-viral vectors have revolutionised in the last 5 years the approaches to tackling pandemics, cancers and genetic diseases. The intrinsic properties of these vectors present new separation challenges to their manufacture in terms of both the process-related impurities to be removed and the complex labile nature of the target products. These characteristics make them susceptible to heterogeneity and the formation of product-related impurities. Conventional polyethersulfone membrane filters used for sterile filtration and ultrafiltration of viral vectors and lipid nanoparticles can display limited selectivity and cause product losses. To address these challenges, novel membrane materials and fabrication techniques to overcome the boundary of selectivity-permeability performance have become of interest. Isoporous membranes with well-defined pore size and pore dispersity at the nano-scale show promising separation performance but have only been demonstrated at small scales to date. This review summarises the decision process for the development of new membrane candidates for vector manufacturing in genomic medicine, including membranes fabricated by lithography, track-etched membranes, anodic aluminium oxide (AAO) membranes and self-assembled block copolymer membranes. By comparing these membranes to existing commercially available products, the possible advantages presented by novel materials and fabrication approaches are identified

Global Stability of a Premixed Reaction Zone (Time-Dependent Liñan’s Problem)

Global stability properties of a premixed, three-dimensional reaction zone are considered. In the nonadiabatic case (i.e., when there is a heat exchange between the reaction zone and the burned gases) there is a unique, spatially one-dimensional steady state that is shown to be unstable (respectively, asymptotically stable) if the reaction zone is cooled (respectively, heated) by the burned mixture. In the adiabatic case, there is a unique (up to spatial translations) steady state that is shown to be stable. In addition, the large-time asymptotic behavior of the solution is analyzed to obtain sufficient conditions on the initial data for stabilization. Previous partial numerical results on linear stability of one-dimensional reaction zones are thereby confirmed and extended

Lensfree optofluidic plasmonic sensor for real-time and label-free monitoring of molecular binding events over a wide field-of-view

We demonstrate a high-throughput biosensing device that utilizes microfluidics based plasmonic microarrays incorporated with dual-color on-chip imaging toward real-time and label-free monitoring of biomolecular interactions over a wide field-of-view of >20 mm^2. Weighing 40 grams with 8.8 cm in height, this biosensor utilizes an opto-electronic imager chip to record the diffraction patterns of plasmonic nanoapertures embedded within microfluidic channels, enabling real-time analyte exchange. This plasmonic chip is simultaneously illuminated by two different light-emitting-diodes that are spectrally located at the right and left sides of the plasmonic resonance mode, yielding two different diffraction patterns for each nanoaperture array. Refractive index changes of the medium surrounding the near-field of the nanostructures, e.g., due to molecular binding events, induce a frequency shift in the plasmonic modes of the nanoaperture array, causing a signal enhancement in one of the diffraction patterns while suppressing the other. Based on ratiometric analysis of these diffraction images acquired at the detector-array, we demonstrate the proof-of-concept of this biosensor by monitoring in real-time biomolecular interactions of protein A/G with immunoglobulin G (IgG) antibody. For high-throughput on-chip fabrication of these biosensors, we also introduce a deep ultra-violet lithography technique to simultaneously pattern thousands of plasmonic arrays in a cost-effective manner

Field-portable optofluidic plasmonic biosensor for wide-field and label-free monitoring of molecular interactions

We demonstrate a field-portable optofluidic plasmonic sensing device, weighing 40 g and 7.5 cm in height, which merges plasmonic microarrays with dual-wavelength lensfree on-chip imaging for real-time monitoring of protein binding kinetics

Identification of new sources of resistance to RHBV- rice hoja blanca virus

With the aim to find new sources of resistance to rice hoja blanca (white leaf) disease, transmitted by the insect Tagosodes orizicolus, 660 genotypes were evaluated under greenhouse and field conditions. Seven resistant genotypes were identified, and genomic studies were performed to demonstrate that the resistance in these sources is genetically different from that of Fedearroz 2000, which is currently the variety with the most resistance to hoja blanca. These new resistance sources constitute a resource that can be used to sustainably extend hoja blanca disease management throughout all of the rice-growing regions of tropical America. This is the first report of hoja blanca resistance in indica rice and different from that of Fedearroz 2000

The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegeneration characterized by the abnormal accumulation of hyperphosphorylated tau protein within the brain. Like many other neurodegenerative conditions, at present, CTE can only be definitively diagnosed by post-mortem examination of brain tissue. As the first part of a series of consensus panels funded by the NINDS/NIBIB to define the neuropathological criteria for CTE, preliminary neuropathological criteria were used by 7 neuropathologists to blindly evaluate 25 cases of various tauopathies, including CTE, Alzheimer's disease, progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, primary age-related tauopathy, and parkinsonism dementia complex of Guam. The results demonstrated that there was good agreement among the neuropathologists who reviewed the cases (Cohen's kappa, 0.67) and even better agreement between reviewers and the diagnosis of CTE (Cohen's kappa, 0.78). Based on these results, the panel defined the pathognomonic lesion of CTE as an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern. The group also defined supportive but non-specific p-tau-immunoreactive features of CTE as: pretangles and NFTs affecting superficial layers (layers II-III) of cerebral cortex; pretangles, NFTs or extracellular tangles in CA2 and pretangles and proximal dendritic swellings in CA4 of the hippocampus; neuronal and astrocytic aggregates in subcortical nuclei; thorn-shaped astrocytes at the glial limitans of the subpial and periventricular regions; and large grain-like and dot-like structures. Supportive non-p-tau pathologies include TDP-43 immunoreactive neuronal cytoplasmic inclusions and dot-like structures in the hippocampus, anteromedial temporal cortex and amygdala. The panel also recommended a minimum blocking and staining scheme for pathological evaluation and made recommendations for future study. This study provides the first step towards the development of validated neuropathological criteria for CTE and will pave the way towards future clinical and mechanistic studies

Chern-Simons Theory as the Large Mass Limit of Topologically Massive Yang-Mills Theory

We study quantum Chern-Simons theory as the large mass limit of the limit $D\to 3$ of dimensionally regularized topologically massive Yang-Mills theory. This approach can also be interpreted as a BRS-invariant hybrid regularization of Chern-Simons theory, consisting of a higher-covariant derivative Yang-Mills term plus dimensional regularization. Working in the Landau gauge, we compute radiative corrections up to second order in perturbation theory and show that there is no two-loop correction to the one-loop shift $k\rightarrow k+ c_{\scriptscriptstyle V},\,\,k$ being the bare Chern-Simons parameter. In passing we also prove by explicit computation that topologically massive Yang-Mills theory is UV finite.Comment: 64 pages without figures (10 figures), DAMTP 91-34, LPTHE 91-61, NBI-HE 91-55, UGMS 91-2