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At least 667 records · Page 37

Exploring the Genetic Basis of Wild Boar ( Sus scrofa ) and Its Connection to Classical Swine Fever Spread

Classical swine fever (CSF) is the one of the most devastating contagious diseases in domestic swine and wild boar/pigs (Sus scrofa). Population genetics is often used to estimate animal dispersal and can also help evaluate host population connectivity, which is crucial for understanding pathogen dispersal. We surveyed genetic population structure of boars using MIG-seq analysis to clarify the geographic barriers that influence boar dispersal in north-central Japan and to demonstrate the relationship between the spread of CSF infection among boars and their population structure. We obtained 382 single-nucleotide polymorphisms from 348 wild boar samples, and the results of STRUCTURE analysis indicated that the highest ΔK value was at K = 2, followed by K = 4. Based on these results, it is evident that the Abukuma river, a major river within north-central Japan, does not act as a barrier to the gene flow of boars, but rather that human infrastructure hinders their dispersal. Further, according to the time series change in the capture site of CSF-infected wild boar and the sum of the probability of belonging to each of the four clades in individual CSF-infected wild boar, our results indicated that the genetic structure of boar populations was correlated with the outbreak pathway of CSF across our study region. Our study suggests that predictions of disease spread, especially for widely distributed host species, is challenging because of the risk of cryptic breaks and changes in wide range connectivity; however, understanding the genetic population structure of wild boar can be a useful tool for predicting the spread of CSF. We concluded that genetic analysis of host population structure may have the possibility to improve predictions of the future dynamics of disease spread.

60 APPLIED LIFE SCIENCES↗

Structural insight into the inactivation of Mycobacterium tuberculosis non-classical transpeptidase Ldt Mt2 by biapenem and tebipenem

Background: The carbapenem subclass of β-lactams is among the most potent antibiotics available today. Emerging evidence shows that, unlike other subclasses of β-lactams, carbapenems bind to and inhibit non-classical transpeptidases (L,D-transpeptidases) that generate 3 → 3 linkages in bacterial peptidoglycan. The carbapenems biapenem and tebipenem exhibit therapeutically valuable potencies against Mycobacterium tuberculosis (Mtb). Results: Here, we report the X-ray crystal structures of Mtb L,D-transpeptidase-2 (Ldt Mt2 ) complexed with biapenem or tebipenem. Despite significant variations in carbapenem sulfur side chains, biapenem and tebipenem ultimately form an identical adduct that docks to the outer cavity of Ldt Mt2 . We propose that this common adduct is an enzyme catalyzed decomposition of the carbapenem adduct by a mechanism similar to S-conjugate elimination by β-lyases. Conclusion: The results presented here demonstrate biapenem and tebipenem bind to the outer cavity of Ldt Mt2 , covalently inactivate the enzyme, and subsequently degrade via an S-conjugate elimination mechanism. We discuss structure based drug design based on the findings and propose that the S-conjugate elimination can be leveraged to design novel agents to deliver and locally release antimicrobial factors to act synergistically with the carbapenem carrier.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Unveiling a classical mutant in the context of the GH 3 β-glucosidase family in Neurospora crassa

Classical fungal mutant strains obtained by mutagenesis have helped to elucidate fundamental metabolic pathways in the past. In the filamentous fungus Neurospora crassa, the gluc-1 strain was isolated long ago and characterized by its low level of β-glucosidase activity, which is essential for the degradation of cellulose, the most abundant biopolymer on Earth and the main polymeric component of the plant cell wall. Based on genomic resequencing, we hypothesized that the causative mutation resides in the β-glucosidase gene gh3-3 (bgl6, NCU08755). In this work, growth patterns, enzymatic activities and sugar utilization rates were analyzed in several mutant and overexpression strains related to gluc-1 and gh3-3. In addition, different mutants affected in the degradation and transport of cellobiose were analyzed. While overexpression of gh3-3 led to the recovery of β-glucosidase activity in the gluc-1 mutant, as well as normal utilization of cellobiose, the full gene deletion strain Δgh3-3 was found to behave differently than gluc-1 with lower secreted β-glucosidase activity, indicating a dominant role of the amino acid substitution in the point mutated gh3-3 gene of gluc-1. Our results furthermore confirm that GH3-3 is the major extracellular β-glucosidase in N. crassa and demonstrate that the two cellodextrin transporters CDT-1 and CDT-2 are essential for growth on cellobiose when the three main N. crassa β-glucosidases are absent. Overall, these findings provide valuable insight into the mechanisms of cellulose utilization in filamentous fungi, being an essential step in the efficient production of biorefinable sugars from agricultural and forestry plant biomass.

60 APPLIED LIFE SCIENCES↗

Evaluating the Rate of Upgrade to Invasive Breast Cancer and/or Ductal Carcinoma In Situ Following a Core Biopsy Diagnosis of Non-classic Lobular Carcinoma In Situ

Background: A diagnosis of non-classic lobular carcinoma in situ (NC-LCIS) encompasses a variety of lesions with poorly characterized natural history. We evaluated upgrade rates and factors associated with upgrade to malignancy following a core biopsy diagnosis of NC-LCIS, and its natural history. Methods: Upon Institutional Review Board approval, pathology databases were searched for NC-LCIS core biopsy diagnoses (carcinoma in situ [CIS], CIS with ductal and lobular features [CIS/DLF], pleomorphic LCIS [P-LCIS], variant LCIS [V-LCIS], LCIS with necrosis). Cases with available core and excision pathology were included, while cases with concurrent ipsilateral invasive carcinoma (IC), ductal carcinoma in situ (DCIS), and/or atypical ductal hyperplasia were excluded. Results: Overall, 121 NC-LCIS cases were identified from 1998 to 2017. We excluded 46 cases with concurrent cancer; 75 patients with 76 NC-LCIS core biopsy diagnoses followed by excision formed our study cohort. Median age was 56 years (range 41–83), and all imaging findings were classified as Breast Imaging Reporting and Data System 4; calcifications were the most common biopsy indication (80%). Excision yielded malignancy in 27 (36%) patients (IC 17, 63%; DCIS alone 10, 37%). We were unable to identify radiologic or pathologic features predictive of upgrade. Of 49 pure NC-LCIS cases, 15 (31%) had mastectomy, 9 (18%) had excision and radiation, and 25 (51%) had excision alone. At a median follow-up of 58 months (range 1–224), 1/25 (4%) patients with excision alone developed ipsilateral DCIS 14 months later. Conclusions: In this series of NC-LCIS, 36% of cases were upgraded, supporting routine excision. We were unable to identify predictors of upgrade. Among 25 patients with pure NC-LCIS, only one patient developed a future ipsilateral cancer. Further study of the natural history of NC-LCIS is warranted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Proposal for a quantum random number generator using coherent light and a non-classical observable

The prototype quantum random number (random bit) generator (QRNG) consists of one photon at a time falling on a 50:50 beam splitter followed by random detection in one or the other output beams due to the irreducible probabilistic nature of quantum mechanics. Due to the difficulties in producing single photons on demand, in practice, pulses of weak coherent (laser) light are used. In this paper, we take a different approach, one that uses moderate coherent light. It is shown that a QRNG can be implemented by performing photon-number parity measurements. For moderate coherent light, the probabilities of obtaining even or odd parity in photon counts are 0.5 each. Photon counting with single-photon resolution can be performed through use of a cascade of beam splitters and single-photon detectors, as was done recently in a photon-number parity-based interferometry experiment involving coherent light. We highlight the point that unlike most quantum-based random number generators, our proposal does not require the use of classical de-biasing algorithms or post-processing of the generated bit sequence.

Gerry, Christopher C.↗

Temporal serum neurofilament light chain concentrations in sheep inoculated with the agent of classical scrapie

Objective: Neurofilament light chain (Nf-L) has been used to detect neuroaxonal damage in the brain caused by physical injury or disease. The purpose of this study was to determine if serum Nf-L could be used as a biomarker for pre-symptomatic detection of scrapie in sheep. Methods: Four sheep with prion protein genotype AVQQ were intranasally inoculated with the classical scrapie strain x124. Blood was collected every 4 weeks until 44 weeks post-inoculation, at which point weekly collection commenced. Serum was analyzed using single molecule array (Quanterix SR-X) to evaluate Nf-L concentrations. Results: Scrapie was confirmed in each sheep by testing homogenized brainstem at the level of the obex with a commercially available enzyme immunoassay. Increased serum Nf-L concentrations were identified above the determined cutoff during the last tenth of the respective incubation period for each sheep. Throughout the time course study, PrP Sc accumulation was not detected antemortem by immunohistochemistry in rectal tissue at any timepoint for any sheep. RT-QuIC results were inconsistently positive throughout the timepoints tested for each sheep; however, each sheep had at least one timepoint detected positive. When assessing serum Nf-L utility using receiver operator characteristic curves against different clinical parameters, such as asymptomatic and symptomatic (pruritus or neurologic signs), results showed that Nf-L was most useful at being an indicator of disease only late in disease progression when neurologic signs were present. Conclusion: Serum Nf-L concentrations in the cohort of sheep increased as disease progressed; however, serum Nf-L did not increase during the presymptomatic window. The levels increased substantially throughout the final 10% of the animals’ scrapie incubation period when other clinical signs were present. Serum Nf-L is not a reliable biomarker for pre-clinical detection of scrapie.

59 BASIC BIOLOGICAL SCIENCES↗

A new Wilson line-based classical action for gluodynamics

We develop a new classical action that in addition to \mathrm{MHV} M H V vertices contains also \mathrm{N^kMHV} N k M H V vertices, where 1\leq k \leq n-4 1 ≤ k ≤ n − 4 with n n the number of external legs. The lowest order vertex is the four-point MHV vertex – there is no three point vertex and thus the amplitude calculation involves fewer vertices than in the CSW method. The action is obtained by a canonical transformation of the Yang-Mills action in the light-cone gauge, where the field transformations are based on Wilson line functionals.

KAKKAD, HIREN↗

Tuning the critical Li intercalation concentrations for MoX 2 bilayer phase transitions using classical and machine learning approaches

Transition metal dichalcogenides (TMDs) such as MoX 2 are known to undergo a structural phase transformation as well as a change in the electronic conductivity upon Li intercalation. These properties make them candidates for charge tunable ion-insertion materials that could be used in electro-chemical devices for neuromorphic computing applications. In this work we study the phase stability and electronic structure of Li-intercalated bilayer MoX 2 with X=S, Se or Te. Using first-principles calculations in combination with classical and machine learning modeling approaches we find that the energy needed to stabilize the conductive phase decreases with increasing atomic mass of the chalcogen atom X. A similar decreasing trend is found in the threshold Li concentration where the structural phase transition takes place. While the electronic conductivity increases with increasing ion concentration at low concentrations, we do not observe a conductivity jump at the phase transition point.

36 MATERIALS SCIENCE↗

Covariant classical charged particle motion in a plane electromagnetic wave revisited

We revisit the covariant formulation of a charged particle’s motion under the influence of a plane electromagnetic wave in classical picture. In the first case, we reproduce Meyer’s result by solving relativistic equation of motion ignoring radiation reaction in vacuum assuming zero mass approximation or null vector case ($k^µk_µ = k^2 = 0$). Then, we extend this approach to include the medium effects as perturbations in the propagation of electromagnetic wave (i. e. $k^2 ≠ 0$) and explore the effects of these perturbations in mass shift of the particle.

43 PARTICLE ACCELERATORS↗

Interesting Isomers - From classic nuclear physics to dark matter - [Slides]

The physics of isomers is almost a century old. While a lot of isomers are studied, the most extreme cases remain unexplored. Testing classic nuclear physics in the extrema. A door into dark sector that is allows us to look for DM types that are not accessible in larger efforts.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Critical thermonuclear reactions in classical novae and type I X-ray bursts

The goal of this project was to experimentally constrain the nuclear reaction rates whose uncertainties have the largest impact on models of classical novae and Type-I X-ray bursts. These astrophysical events occur when a white dwarf or neutron star, respectively, accretes hydrogen and helium from a companion star until a thermonuclear runaway ensues. The primary reactions of interest to this project for novae and X-ray bursts are 30 P(ρ,γ) 31 S and 15 O(α,γ) 19 Ne. The project methodology was to develop a new radiation detection system in two phases to measure the low-energy beta-delayed particle emissions of 31 Cl and 20 Mg at the National Superconducting Cyclotron Laboratory (NSCL) in order to constrain these two reaction rates. In particular, a gas-filled charged-particle detector was to be designed, constructed and operated, in concert with the SeGA array.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Hydrodynamic Simulations of Classical Novae: Accretion onto CO White Dwarfs as SN Ia Progenitors

We report on our continuing studies of Classical Nova explosions by following the evolution of thermonuclear runaways (TNRs) on carbon-oxygen (CO) white dwarfs (WDs). We have varied both the mass of the WD and the composition of the accreted material. Rather than assuming that the material has mixed from the beginning, we now rely on the results of the multidimensional (multi-D) studies of mixing as a consequence of the TNRs in WDs that accreted only Solar matter. The multi-D studies find that mixing with the core occurs after the TNR is well underway and reach enrichment levels in agreement with observations of the ejecta abundances. We report on 3 studies in this paper. First, simulations in which we accrete only Solar matter with NOVA (our 1-D, fully implicit, hydro code). Second, we use MESA for similar studies in which we accrete only Solar material and compare the results. Third, we accrete Solar matter until the TNR is initiated and then switch the composition in the accreted layers to a mixed composition: either 25% core and 75% Solar or 50% core and 50% Solar. The amount of accreted material is inversely proportional to the initial 12 C abundance. Thus, accreting Solar material results in more material to fuel the outburst - much larger than in the earlier studies where mixed materials were used from the beginning. We tabulate the amount of ejected gases, their velocities, and abundances. We predict the amount of 7 Li and 7 Be produced and ejected by the explosion and compare our predictions to our Large Binocular Telescope (LBT) high dispersion spectra which determined the abundance of 7 Li in nova V5668 Sgr. Finally, many of these simulations eject significantly less mass than accreted and, therefore, the WD is growing in mass toward the Chandrasekhar Limit.

79 ASTRONOMY AND ASTROPHYSICS↗

A Review of Classical Swine Fever Virus and Routes of Introduction into the United States and the Potential for Virus Establishment

Classical swine fever (CSF) is caused by CSF virus (CSFV) which can be the source of substantial morbidity and mortality events in affected swine. The disease can take one of several forms (acute, chronic, or prenatal) and depending on the virulence of the inoculating strain may result in a lethal infection irrespective of the form acquired. Because of the disease-free status of the United States and the high cost of a viral incursion, a summary of US vulnerabilities for viral introduction and persistence is provided. The legal importation of live animals as well as animal products, byproducts, and animal feed serve as a potential route of viral introduction. Current import regulations are described as are mitigation strategies that are commonly utilized to prevent pathogens, including CSFV, from entering the US. The illegal movement of suids and their products as well as an event of bioterrorism are both feasible routes of viral introduction but are difficult to restrict or regulate. Ultimately, recommendations are made for data that would be useful in the event of a viral incursion. Population and density mapping for feral swine across the United States would be valuable in the event of a viral introduction or spillover; density data could further contribute to understanding the risk of infection in domestic swine. Additionally, ecological and behavioral studies, including those that evaluate the effects of anthropogenic food sources that support feral swine densities far above the carrying capacity would provide invaluable insight to our understanding of how human interventions affect feral swine populations. Further analyses to determine the sampling strategies necessary to detect low levels of antibody prevalence in feral swine would also be valuable.

Veterinary Sciences↗

ℤ2 × ℤ2 Equivariant Quantum Neural Networks: Benchmarking against Classical Neural Networks

This paper presents a comparative analysis of the performance of Equivariant Quantum Neural Networks (EQNNs) and Quantum Neural Networks (QNNs), juxtaposed against their classical counterparts: Equivariant Neural Networks (ENNs) and Deep Neural Networks (DNNs). We evaluate the performance of each network with three two-dimensional toy examples for a binary classification task, focusing on model complexity (measured by the number of parameters) and the size of the training dataset. Our results show that the Z2×Z2 EQNN and the QNN provide superior performance for smaller parameter sets and modest training data samples.

Dong, Zhongtian (ORCID:0000000210003454)↗

Assessment of the Reversion to Virulence and Protective Efficacy in Pigs Receiving the Live Attenuated Classical Swine Fever Recombinant Vaccine Candidate FlagT4G

Background/Objectives: Control of classical swine fever virus (CSFV) in endemic countries relies on vaccination using live attenuated vaccines (LAVs). Most of these LAVs do not allow for the differentiation of vaccinated animals from infected animals (DIVA) based on their serological response. FlagT4G vaccine is a novel candidate that confers robust protective immunity early after vaccination and shows DIVA capabilities. Methods: This report presents the characterization of FlagT4G virus in terms of the stability of its genomic and attenuated phenotypes assessed by a reversion to virulence protocol, as well as its protective efficacy by determining the minimal protective dose. Results: Results presented here demonstrate that after five consecutive passages in groups of 5-week-old susceptible domestic pigs, FlagT4G virus remains genetically stable, and its attenuated phenotype remains unaltered. In terms of efficacy, FlagT4G virus induced solid protection against the intranasal challenge with 105 tissue culture infectious dose (TCID50) of virulent field isolate Brescia virus, even with a vaccine dose as low as 102 TCID50. Conclusions: Results presented here indicate that the FlagT4G vaccine may be a useful tool for CSFV control.

Immunology↗