Search

The GapC products of Streptococcus agalactiae, Streptococcus dysgalactiae, and Streptococcus uberis share considerable homology at the DNA and amino acid levels. The high similarity at the protein level suggests that one GapC protein might be used as a single antigen to protect dairy cows against infections with the contagious S. agalactiae and the environmental S. dysgalactiae and S. uberis strains. Despite their similarities, immunization with the S. dysgalactiae GapC did not protect dairy cows from a challenge with S. uberis, suggesting the presence of regions in GapC that are involved in species-specific protection. To produce a single antigen that can be used to protect against all streptococcal mastitis infections, we constructed a GapC chimeric protein using the S. uberis GapC product as the backbone followed by non-conserved peptide regions from the S. agalactiae and S. dysgalactiae GapC proteins. We report that the chimeric GapC protein retains the enzymatic activity of the S. uberis GapC protein. In addition, we fused the chimera to the OmpF and LipoF transport sequences of Escherichia coli and the GapC chimeras were present in membrane fractions of E. coli. These extracts could be the basis of an antigen preparation for use in mastitis vaccines.

The targeting of RNA for the design of novel anti-viral compounds represents an area of vast potential. We have used NMR and computational methods to model the interaction of a series of synthetic inhibitors of the in vitro RNA binding activities of a peptide derived from the transcriptional activator protein, Tat, from human immunodeficiency virus type 1. Inhibition has been measured through the monitering of fluorescence resonance energy transfer between fluorescently labeled peptide and RNA components. A series of compounds containing a bi-aryl heterocycle as one of the three substituents on a benzylic scaffold, induce a novel, inactive TAR conformation by stacking between base-pairs at the site of a three-base bulge within TAR. The development of this series resulted in an enhancement in potency (with Ki < 100 nM in an in vitro assay) and the removal of problematic guanidinium moieties. Ligands from this series can act as inhibitors of Tat-induced transcription in a cell-free system. This study validates the drug design strategy of using a ligand to target the RNA receptor in a non-functional conformation.

Cattle are an important reservoir of Escherichia coli O157:H7 leading to contamination of food and water, and subsequent human disease. This pathogen colonizes its hosts by producing several proteins such as Tir and EspA that are secreted by a type III secretion system. These proteins play a role in colonization of the intestine, suggesting that they might be useful targets for the development of a vaccine to reduce levels of this organism in cattle. Vaccination of cattle with proteins secreted by E. coli O157:H7 significantly reduced the numbers of bacteria shed in feces, the numbers of animals that shed, and the duration of shedding in an experimental challenge model. Vaccination of cattle also significantly (P=0.04) reduced the prevalence of E. coli O157:H7 in a clinical trial conducted in a typical feedlot setting. This strategy suggests it is possible to vaccinate cattle to decrease the level of E. coli O157:H7 shedding for the purpose of reducing the risk of human disease.

The diseases caused by pathogenic Escherichia coli constitute a major economic loss to the poultry industry. The development of a live oral E. coli vaccine to prevent or reduce diseases in poultry had been the objective of our work. Four spontaneous streptomycin-dependent (str-dependent) mutants were generated from a virulent avian strain that contains a mutation in the fur region of the chromosome. Genetic analysis of the mutants indicated that the str-dependent phenotype was due to a base change of C --T at base 272 in the rpsL gene. The mutants were tested for attenuation using the day-old chick model. Day-old birds, in groups of 20, were either challenged with 10(6) colony-forming units (CFU) of the str-dependent mutant, the parent strain (containing the fur mutation), or the wild-type strain without the fur mutation. The parent strain and the wild-type strain were highly virulent, and 80% or more of the birds died. None of the birds challenged with the str-dependent mutants died, indicating attenuation of the mutants. The protective effect of the mutant as a live vaccine against the challenge with 10(6) CFU of the wild-type strain EC317 was investigated. Vaccination by both aerosol (day 1) and oral (days 14 and 28) routes using 10(8) CFU of the str-dependent mutant (EC1598) had no effect on the occurrence of cellulitis in the birds. Two vaccinations given as aerosol on day 1 and given orally on day 14 also had no significant effect on the occurrence of systemic lesions. Three immunizations on days 1, 14, and 28 resulted in a significant reduction in the number of birds with systemic lesions. Antibody titers prior to challenge were not predictive of outcome of challenge.

Synthetic oligodeoxynucleotides (ODN) containing CpG motifs (CpG-ODN) have been shown to be effective immunoprotective agents in murine models for a variety of viral, intracellular bacterial, and protozoan infections. Until now, the use of CpG-ODN to protect against extracellular bacterial infections has not been reported. The objective of this study was to investigate the effect of CpG-ODN against cellulitis and colibacillosis in broiler chickens, using a well-established model. At 22 days of age, birds received CpG-ODN by either the subcutaneous or intramuscular route. Three days later, a virulent isolate of Escherichia coli was applied to a scratch site on the caudal abdominal skin. Birds were examined for 10 days after the E. coli challenge, and pathological and bacteriological assessments were conducted on all birds. The control group of birds receiving no CpG-ODN (2007) had a survival rate of 15%. In contrast, groups that received CpG-ODN (2007) , by either subcutaneous or intramuscular injection, had significantly higher survival rates ( P < 0.0001). Furthermore, the size of the cellulitis lesion was significantly smaller in groups that received CpG-ODN (2007) by the subcutaneous route ( P < 0.01). A dose of as little as 3.16 μg of CpG-ODN (2007) , delivered 3 days prior to challenge by either the subcutaneous or intramuscular route, significantly protected birds against E. coli infection ( P < 0.01). This study demonstrates that CpG-ODN (2007) has both local and systemic protective effects in broiler chickens. This is the first time that CpG-ODN (2007) has been demonstrated to have an immunoprotective effect against an extracellular bacterial infection in any food animal species.

Inclusion body hepatitis (IBH) is one of the major global disease problems, causing significant economic losses to poultry industry of the United States and Canada. The disease is characterized by its sudden onset and high mortalities. Amongst different serotypes of fowl adenoviruses (FAdVs) associated with IBH, serotype 8 of group I FAdV has been isolated from majority of IBH cases. In present studies, we isolated a FAdV from morbid liver of a 17-day-old broiler from a Saskatchewan broiler farm. This newly isolated virus was designated as IBHV(SK). However, based on the sequence analysis of the L1 region of the hexon gene, the IBHV(SK) may be classified as FAdV 8b strain 764. These studies describe for the first time the complete hexon gene sequence of FAdV serotype 8b. Experimental infection of 2-day-old (n = 48) and 2-wk-old (n = 56) chicks caused 83% and 43% mortalities, respectively. Determination of the complete hexon gene sequence of IBHV(SK) with establishment of a disease model in chickens will facilitate the development of type-specific diagnostic reagents and assays for the evaluation of potential experimental vaccines against pathogenic FAdV infections.

Diseases of poultry caused by Escherichia coli result in significant economic loss every year. Specific virulence factors associated with E. coli strains pathogenic for poultry have been identified, but it is likely that others remain to be identified. To identify unique DNA fragments associated with avian strains we used suppression subtractive hybridization. The genome of E. coli K-12 strain MG1655 was subtracted from the genomes of two avian E. coli strains resulting in the identification of 62 fragments specific to the two avian strains. Sequence homology analysis was done and four types of fragments were identified: plasmid sequences, phage sequences, sequences with known function and sequences without any currently known function. Two E. coli collections, a reference collection of diverse strains (ECOR) and a collection of 41 avian isolates, were screened for the presence of 25 of the 62 fragments. We identified nine fragments present in significantly more of the avian strains than of the ECOR strains. Five fragments were in significantly more of the ECOR strains than the avian strains. These results suggested that the nine fragments could play a role in the pathogenesis of E. coli as it relates to diseases of poultry.

The Fur (ferric uptake regulator) protein is a master regulator of iron metabolism in gram-negative bacteria. In the present study, the effect of a partial deletion of the fur gene on the acid-tolerance response and in vivo virulence of avian Escherichia coli was examined. The fur mutant was unable to trigger the acid-tolerance response as observed in the wild-type parent strain. However, the mutant was as virulent as the wild-type parent strain when tested in 1-day-old chickens by subcutaneous inoculation. These data indicate that the fur gene is involved in the acid-tolerance response but not involved in the virulence of E. coli, as detected by the ability to cause septicemia in our experimental infection.Key words: E. coli, fur, acid-tolerance response.

© 2017 Desclozeaux et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. We assessed the effects of two different single-dose anti-Chlamydia pecorum (C. pecorum) vaccines (containing either Major Outer Membrane Protein (3MOMP) or Polymorphic Membrane Protein (Pmp) as antigens) on the immune response of a group of wild koalas. Both vaccines elicited a systemic humoral response as seen by the production of anti-chlamydial IgG antibodies in more than 90% of vaccinated koalas. A mucosal immune response was also observed, with an increase in Chlamydia-specific mucosal IgG and/or IgA antibodies in some koalas post-vaccination. Both vaccines elicited a cell-mediated immune response as measured by the production of the cytokines IFN-γ and IL-17 post-vaccination. To determine the level of protection provided by the vaccines under natural conditions we assessed C. pecorum infection loads and chlamydial disease status of all vaccinated koalas pre-and post-vaccination, compared to a non-vaccinated cohort from the same habitat. The MOMP vaccinated koalas that were infected on the day of vaccination showed significant clearance of their infection at 6 months post-vaccination. In contrast, the number of new infections in the PMP vaccine was similar to the control group, with some koalas progressing to disease. Genotyping of the ompA gene from the C. pecorum strains infecting the vaccinated animals, identified genetic variants of ompA-F genotype and a new genotype ompA-O. We found that those animals that were the least well protected became infected with strains of C. pecorum not covered by the vaccine. In conclusion, a single dose vaccine formulated with either recombinant PmpG or MOMP can elicit both cell-mediated and humoral (systemic and mucosal) immune responses, with the MOMP vaccine showing clearance of infection in all infected koalas. Although the capability of our vaccines to stimulate an adaptive response and be protective needs to be fully evaluated, this work illustrates the necessity to combine epitopes most relevant to a large panel of variable strains with an efficient adjuvant.

We review recent advances in understanding the universal scaling properties of non-equilibrium phase transitions in non-ergodic disordered systems. We discuss dynamical critical points (also known as eigenstate phase transitions) between different many-body localized (MBL) phases, and between MBL and thermal phases., v2: Published version

International audience; Johne’s disease (JD) is a chronic enteric infection of cattle caused by Mycobacterium avium subsp. paratuberculosis (MAP). The high economic cost and potential zoonotic threat of JD have driven efforts to develop tools and approaches to effectively manage this disease within livestock herds. Efforts to control JD through traditional animal management practices are complicated by MAP’s ability to cause long-term environmental contamination as well as difficulties associated with diagnosis of JD in the pre-clinical stages. As such, there is particular emphasis on the development of an effective vaccine. This is a daunting challenge, in large part due to MAP’s ability to subvert protective host immune responses. Accordingly, there is a priority to understand MAP’s interaction with the bovine host: this may inform rational targets and approaches for therapeutic intervention. Here we review the early host defenses encountered by MAP and the strategies employed by the pathogen to avert or subvert these responses, during the critical period between ingestion and the establishment of persistent infection in macrophages.

Respiratory syncytial virus (RSV) causes severe respiratory illness in infants. There are no licensed vaccines to prevent RSV infection. The neonate receives short-term protection from maternally derived antibodies, which, however, can also interfere with the active response to vaccination. A RSV vaccine consisting of a truncated version of the fusion protein formulated with polyI:C, innate defense regulator peptide and polyphosphazene (ΔF/TriAdj), was evaluated in two to three week-old lambs. When delivered intrapulmonary, ΔF/TriAdj elicited IgA production in the lung in addition to a robust systemic response similar to that induced by intramuscular immunization. To investigate potential interference by maternal antibodies, pregnant ewes were vaccinated with ΔF/TriAdj. Lambs born to RSV F-immune or non-immune ewes were then given three vaccinations with ΔF/TriAdj at 3 days, 4 weeks and 8 weeks post-birth. Lambs immunized intramuscularly with ΔF/TriAdj vaccine developed high-affinity ΔF-specific serum IgG and virus neutralizing antibodies, and displayed an increase in the frequency of IFN-γ-secreting cells by in vitro restimulated peripheral blood mononuclear cells. Maternal antibodies did not interfere with the development of an immune response to ΔF/TriAdj in the newborn lambs. These results indicate that immunization of neonates with ΔF/TriAdj is effective even in the face of maternal antibodies.

Continued growth in the number of individuals with dementia residing in assisted living (AL) raises concerns about their safety and protection. In this Forum, we review current AL practices relevant to residents with dementia and present a rationale for examining the government role in protecting these individuals within this context. Since public oversight of AL is currently a state prerogative, we assess states’ regulatory activity across 3 domains closely related to safety and protection of persons with dementia: environmental features, staffing, and use of chemical restraints. We then step back to consider the state policymaking environment and assess the feasibility of developing a minimum standard of regulations from one state to the next. This Forum concludes with a historical comparison between the contemporary AL market and the nursing home care market prior to the Nursing Home Reform Act of 1987, and we discuss how an increased amount of federal interest could improve existing state efforts to protect persons with dementia residing in AL.

As competition for physicians intensifies in the USA, rural areas are at a disadvantage due to challenges unique to rural medical practice. Telemedicine improves access to care not otherwise available in rural settings. Previous studies have found that telemedicine also has positive effects on the work environment, suggesting that telemedicine may improve rural physician recruitment and retention, although few have specifically examined this.Using a mixed-method approach, clients of a single telemedicine service in the Upper Midwestern USA were surveyed and interviewed about their views of the impact of tele-emergency on physician recruitment and retention and the work environment. Surveys were completed by 292 clinical and administrative staff at 71 hospitals and semi-structured interviews were conducted with clinicians and administrators at 16 hospitals.Survey respondents agreed that tele-emergency had a positive effect on physician recruitment and retention and related workplace factors. Interviewees elucidated how the presence of tele-emergency played an important role in enhancing physician confidence, providing educational opportunities, easing burden, and supplementing care, workplace factors that interviewees believed would impact recruitment and retention. However, gains were limited by hospitals' interpretation of the Emergency Medical Treatment and Labor Act as requiring on-site physician coverage even if tele-emergency was used.Results indicate that, all other factors being equal, tele-emergency increases the likelihood of physicians entering and remaining in rural practice. New regulatory guidance by the Centers for Medicare and Medicaid Services related to on-site physician coverage will likely accelerate implementation of tele-emergency services in rural hospitals. Telemedicine may prove to be an increasingly valuable recruitment and retention tool for rural hospitals as competition for physicians intensifies.

Introduction As competition for physicians intensifies in the USA, rural areas are at a disadvantage due to challenges unique to rural medical practice. Telemedicine improves access to care not otherwise available in rural settings. Previous studies have found that telemedicine also has positive effects on the work environment, suggesting that telemedicine may improve rural physician recruitment and retention, although few have specifically examined this. Methods Using a mixed-method approach, clients of a single telemedicine service in the Upper Midwestern USA were surveyed and interviewed about their views of the impact of tele-emergency on physician recruitment and retention and the work environment. Surveys were completed by 292 clinical and administrative staff at 71 hospitals and semi-structured interviews were conducted with clinicians and administrators at 16 hospitals. Results Survey respondents agreed that tele-emergency had a positive effect on physician recruitment and retention and related workplace factors. Interviewees elucidated how the presence of tele-emergency played an important role in enhancing physician confidence, providing educational opportunities, easing burden, and supplementing care, workplace factors that interviewees believed would impact recruitment and retention. However, gains were limited by hospitals' interpretation of the Emergency Medical Treatment and Labor Act as requiring on-site physician coverage even if tele-emergency was used. Conclusions Results indicate that, all other factors being equal, tele-emergency increases the likelihood of physicians entering and remaining in rural practice. New regulatory guidance by the Centers for Medicare and Medicaid Services related to on-site physician coverage will likely accelerate implementation of tele-emergency services in rural hospitals. Telemedicine may prove to be an increasingly valuable recruitment and retention tool for rural hospitals as competition for physicians intensifies.

We consider $d$-dimensional systems which are localized in the absence of interactions, but whose single-particle localization length diverges near a discrete set of (single-particle) energies, with critical exponent $\ensuremath{\nu}$. This class includes disordered systems with intrinsic or symmetry protected topological bands, such as disordered integer quantum Hall insulators. We show that such marginally localized systems exhibit anomalous properties intermediate between localized and extended, including vanishing dc conductivity but subdiffusive dynamics, and fractal entanglement (an entanglement entropy with a scaling intermediate between area and volume law). We investigate the stability of marginal localization in the presence of interactions, and argue that arbitrarily weak short-range interactions trigger delocalization for partially filled bands at nonzero energy density if $\ensuremath{\nu}\ensuremath{\ge}1/d$. We use the Harris-Chayes bound $\ensuremath{\nu}\ensuremath{\ge}2/d$ to conclude that marginal localization is generically unstable in the presence of interactions. Our results suggest the impossibility of stabilizing quantized Hall conductance at nonzero energy density.

In mean-field descriptions of nodal d-wave superconductors, generic edges exhibit dispersionless Majorana fermion bands at zero energy. These states give rise to an extensive ground-state degeneracy, and are protected by time-reversal symmetry. We argue that the infinite density of states of these flat bands make them inherently unstable to interactions, and show that repulsive interactions lead to edge ferromagnetism which splits the flat bands. This edge ferromagnetism offers an explanation for the observation of the splitting of zero-bias peaks in edge tunneling in high-Tc cuprate superconductors. We argue that this mechanism for splitting is more likely than previously proposed scenarios and describe its experimental consequences.

Condensed matter systems provide a rich setting to realize Dirac and Majorana fermionic excitations and the possibility to manipulate them in materials for potential applications. Recently, it has been proposed that Weyl fermions, which are chiral, massless particles, can emerge in certain bulk materials or in topological insulator multilayers and can produce unusual transport properties, such as charge pumping driven by a chiral anomaly. A pair of Weyl fermions protected by crystalline symmetry, effectively forming a massless Dirac fermion, has been predicted to appear as low energy excitations in a number of candidate materials termed three-dimensional (3D) Dirac semimetals. Here we report scanning tunneling microscopy (STM) measurements at sub-Kelvin temperatures and high magnetic fields on one promising host material, the II-V semiconductor Cd3As2. Our study provides the first atomic scale probe of Cd3As2, showing that defects mostly influence the valence band, consistent with the observation of ultra-high mobility carriers in the conduction band. By combining Landau level spectroscopy and quasiparticle interference (QPI), we distinguish a large spin-splitting of the conduction band in a magnetic field and its extended Dirac-like dispersion above the expected regime. A model band structure consistent with our experimental findings suggests that for a specific orientation of the applied magnetic field, Weyl fermions are the low-energy excitations in Cd3As2., Main Text: 17 pages, 4 figures. Supplementary Materials: 12 pages, 7 figures, Nature Materials (2014)

Condensed-matter systems provide a rich setting to realize Dirac and Majorana fermionic excitations as well as the possibility to manipulate them for potential applications. It has recently been proposed that chiral, massless particles known as Weyl fermions can emerge in certain bulk materials or in topological insulator multilayers and give rise to unusual transport properties, such as charge pumping driven by a chiral anomaly. A pair of Weyl fermions protected by crystalline symmetry effectively forming a massless Dirac fermion has been predicted to appear as low-energy excitations in a number of materials termed three-dimensional Dirac semimetals. Here we report scanning tunnelling microscopy measurements at sub-kelvin temperatures and high magnetic fields on the II-V semiconductor Cd3As2. We probe this system down to atomic length scales, and show that defects mostly influence the valence band, consistent with the observation of ultrahigh-mobility carriers in the conduction band. By combining Landau level spectroscopy and quasiparticle interference, we distinguish a large spin-splitting of the conduction band in a magnetic field and its extended Dirac-like dispersion above the expected regime. A model band structure consistent with our experimental findings suggests that for a magnetic field applied along the axis of the Dirac points, Weyl fermions are the low-energy excitations in Cd3As2.

Prions are a novel form of infectivity based on the misfolding of a self-protein (PrP(C)) into a pathological, infectious isomer (PrP(Sc)). The current uncontrolled spread of chronic wasting disease in cervids, coupled with the demonstrated zoonotic nature of select livestock prion diseases, highlights the urgent need for disease management tools. While there is proof-of-principle evidence for a prion vaccine, these efforts are complicated by the challenges and risks associated with induction of immune responses to a self-protein. Our priority is to develop a PrP(Sc)-specific prion vaccine based on epitopes that are uniquely exposed upon misfolding. These disease specific epitopes (DSEs) have the potential to enable specific targeting of the pathological species through immunotherapy. Here we review outcomes of the translation of a prion DSE into a PrP(Sc)-specific vaccine based on the criteria of immunogenicity, safety and specificity.

Tele-emergency services provide immediate and synchronous audio/video connections, most commonly between rural low-volume hospitals and an urban "hub" emergency department. We performed a systematic literature review to identify tele-emergency models and outcomes. We then studied a large tele-emergency service in the upper Midwest. We sent a user survey to all seventy-one hospitals that used the service and received 292 replies. We also conducted telephone interviews and site visits with ninety clinicians and administrators at twenty-nine of these hospitals. Participants reported that tele-emergency improves clinical quality, expands the care team, increases resources during critical events, shortens time to care, improves care coordination, promotes patient-centered care, improves the recruitment of family physicians, and stabilizes the rural hospital patient base. However, inconsistent reimbursement policy, cross-state licensing barriers, and other regulations hinder tele-emergency implementation. New value-based payment systems have the potential to reduce these barriers and accelerate tele-emergency expansion.

International audience; AbstractAn alarming increase in emergence of antibiotic resistance among pathogens worldwide has become a serious threat to our ability to treat infectious diseases according to the World Health Organization. Extensive use of antibiotics by livestock producers promotes the spread of new resistant strains, some of zoonotic concern, which increases food-borne illness in humans and causes significant economic burden on healthcare systems. Furthermore, consumer preferences for meat/poultry/fish produced without the use of antibiotics shape today’s market demand. So, it is viewed as inevitable by the One Health Initiative that humans need to reduce the use of antibiotics and turn to alternative, improved means to control disease: vaccination and prophylactics. Besides the intense research focused on novel therapeutic molecules, both these strategies rely heavily on the availability of cost-effective, efficient and scalable production platforms which will allow large-volume manufacturing for vaccines, antibodies and other biopharmaceuticals. Within this context, plant-based platforms for production of recombinant therapeutic proteins offer significant advantages over conventional expression systems, including lack of animal pathogens, low production costs, fast turnaround and response times and rapid, nearly-unlimited scalability. Also, because dried leaves and seeds can be stored at room temperature for lengthy periods without loss of recombinant proteins, plant expression systems have the potential to offer lucrative benefits from the development of edible vaccines and prophylactics, as these would not require “cold chain” storage and transportation, and could be administered in mass volumes with minimal processing. Several biotechnology companies currently have developed and adopted plant-based platforms for commercial production of recombinant protein therapeutics. In this manuscript, we outline the challenges in the process of livestock immunization as well as the current plant biotechnology developments aimed to address these challenges.

We study the infinite-temperature properties of an infinite sequence of random quantum spin chains using a real-space renormalization group approach, and demonstrate that they exhibit non-ergodic behavior at strong disorder. The analysis is conveniently implemented in terms of SU(2)$_k$ anyon chains that include the Ising and Potts chains as notable examples. Highly excited eigenstates of these systems exhibit properties usually associated with quantum critical ground states, leading us to dub them "quantum critical glasses". We argue that random-bond Heisenberg chains self-thermalize and that the excited-state entanglement crosses over from volume-law to logarithmic scaling at a length scale that diverges in the Heisenberg limit $k\rightarrow\infty$. The excited state fixed points are generically distinct from their ground state counterparts, and represent novel non-equilibrium critical phases of matter., Comment: 4.5+12 pages. 2 figures. v5: Published version

The surface states of Weyl semi-metals (SM's) consist of disjointed Fermi-arcs. This unusual surface-Fermiology provides a fingerprint of the topological features of the bulk Weyl-phase. Using a combination of semiclassical and numerical methods, we show that, in contrast to naive expectation, there are closed magnetic orbits involving the open- surface Fermi-arcs. Below a critical field strength that depends on sample thickness, these orbits produce periodic quantum oscillations of the density of states in a magnetic field, enabling a variety of experimental probes of the unconventional Fermi-arc surface states. The orbits are also essential for reproducing the bulk chiral anomaly in a finite slab. These results are then extended to the closely related and recently discovered 3D Dirac SM materials, including Cd3As2 and Na3Bi, which are doubled copies of Weyl semi-metals protected by crystal symmetry. Despite the fact that the protecting crystal symmetry is broken by a surface, we show that Dirac materials can still host unconventional surface-states, which can be detected in quantum oscillations experiments., Comment: 5 pages, 3 Figures, plus supplementary appendices

Direct coupling between gapless bosons and a Fermi surface results in the destruction of Landau quasiparticles and a breakdown of Fermi liquid theory. Such a non-Fermi liquid phase arises in spin-orbit coupled ferromagnets with spontaneously broken continuous symmetries due to strong coupling between rotational Goldstone modes and itinerant electrons. These systems provide an experimentally accessible context for studying non-Fermi liquid physics. Possible examples include low-density Rashba coupled electron gases, which have a natural tendency towards spontaneous ferromagnetism, or topological insulator surface states with proximity-induced ferromagnetism. Crucially, unlike the related case of a spontaneous nematic distortion of the Fermi surface, for which the non-Fermi liquid regime is expected to be masked by a superconducting dome, we show that the non-Fermi liquid phase in spin-orbit coupled ferromagnets is stable., Comment: 14 pages; typos fixed and transport/disorder sections revised

Observations of Mercury in the mid infrared (8–12.5 μm region) obtained over a variety of longitudes using the Fourier Transform Spectrometer (FTS) on the McMath-Pierce 1.5 m solar telescope at Kitt Peak reveal low-contrast spectra, except in cases where atmospheric noise or difficulties in guiding the telescope caused spurious signals. Although there are features that are suggestive of emissivity maxima (Christiansen features), their proximity to the telluric absorption band, and the noise in the spectra, preclude their unambiguous interpretation. We see little evidence of reststrahlen bands in our data; however, there are strong indications of transparency features. A shallow emissivity minimum occurs at 12 μm in the spectra centered at 80°, 256°, and 266° Hermean longitudes. A minimum occurs at 12.5 μm in the spectra centered at 15°, and a doublet minimum, with one trough at 12.2 μm and a second trough at 12.4–12.6 μm, is seen in the spectra centered at 229°. These features indicate the presence of a fine powder on the Mercurian surface, and their low spectral contrast suggests a significant percentage of agglutinitic material. On the basis of the position of the transparency features, we conclude that our spectra are indicative of intermediate, mafic, and ultramafic rock types. Further specificity is not warranted by the data.

We measured sodium emission above the lunar equator over a range of lunar altitudes from 100 to 4000 km. The measurements were repeated approximately every 24 hours from June 7 to 16, 1998, covering the period during which the Moon passed through the Earth's magnetotail. Sodium temperatures derived from the altitude dependence of emission intensity ranged from 1200 to 2900 K. This result supports the view that photodesorption is a primary source of sodium in the exosphere since the most probable temperature of sodium form this source is in this range. Passage of the Moon through the Earth's magnetotail (where solar wind is essentially absent) affected the sodium density, such that it was higher before the Moon entered the Earth's magnetotail than after the Moon left it. This suggests that the solar wind plays a role in production of lunar sodium. We propose that its function is to mobilize sodium and bring it to the surface, where photodesorption can eject it into the exosphere. A two-step process such as this could help to explain the latitude dependence of sodium density, which varies as the second or higher power of cosine latitude.

The velocity distribution of atoms in an exosphere can be used to constrain source and loss processes. The velocity distribution itself can be constrained by observing the line profile of an atmospheric emission line. The only atomic species known to exist in the Hermean exosphere that has a strong enough resonance transition in the visible spectrum that its line profile can be observed from the ground with existing instruments is sodium. Line profiles of the sodium D2 emission (5889 A) were obtained at two facilities. On 29 and 30 May 1997, we obtained line profiles with the 107 inch telescope at The McDonald Observatory at coude focus. On 6 January 1998, we obtained line profiles at the Anglo–Australian telescope. The line profiles show that the sodium in Mercury’s atmosphere is at least 700 K hotter than the surface temperature throughout the atmosphere. This implies that the interaction of the Na atoms with the surface is governed by energetic processes.

We imaged Mercury in sodium D 1 and D 2 emission for 6 days during the period 13–20 November 1997 using a 10×10-arc s aperture image slicer coupled to a high-resolution spectrograph. We corrected the sodium images for smearing by the terrestrial atmosphere by computing the actual seeing function from surface reflection images, and used this function to correct the sodium images. During the period of observation, large daily changes took place in both the total amount of sodium and its distribution over the planet. Total sodium increased by a factor of about 3 during this period. The sodium emission was brightest at longitudes near the subsolar longitude in the range 130–150°, with excess sodium at northern latitudes on some days, and excess sodium at southern latitudes on other days. There are no obviously outstanding geologic features at this longitude. The rapid changes observed during this period suggest a connection with solar activity, since the planet itself is apparently geologically inactive. The F10.7 cm solar flux during this period varied only slightly, with an increase of about 15%, probably insufficient to account for the observed changes. However, there were a number of coronal mass ejection (CME) events, some of which were directed towards the general area of Mercury. We suggest that the changes in the visible neutral sodium atmosphere might be a result of the effect of CMEs on Mercury.

The transferrin-binding proteins TbpA and TbpB from Pasteurella haemolytica biotype A serotype 1 were tested for their ability to confer protection against experimental P. haemolytica infection when administered to calves in vaccine formulations containing one or both antigens. Vaccine groups included TbpB (single immunization), TbpB (two immunizations), TbpA, TbpA+TbpB and a placebo. All animals that received TbpB had measurable antibody titres against the antigen at the time of challenge, while those that received TbpA did not show an antibody response. The TbpA+TbpB group showed the best protection against experimental challenge. Protection correlated with anti-TbpB antibody levels. The enhanced protection in the TbpA+TbpB group suggests TbpA contributed to protection through the induction of a non-antibody-mediated immune response. Sera from the TbpB-immunized animals was cross-reactive with TbpBs from other P. haemolytica serotypes.

The mechanisms used by Haemophilus somnus to survive and multiply within bovine mononuclear phagocytes are not fully understood. In order to study the interaction between bovine mononuclear phagocytes and H. somnus, a colorimetric assay using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenylItetrazolium bromide (MTT) was developed to assess the survival of H. somnus within cultured bovine blood monocytes (BBM). Using this system, it was found that H. somnus was able to survive within BMM in vitro, and the kinetics of its survival were similar to that seen in BBM isolated from experimentally infected cattle. Using ultrastructural studies, it was possible to demonstrate the survival of H. somnus in freshly isolated bovine mononuclear phagocytes in membrane-bound vacuoles. To determine if activation of macrophage function would result in elimination of intracellular H. somnus, BBM were treated with E. coli lipopolysaccharide (LPS) or recombinant bovine (rBo) cytokines, interferon-gamma (IFN-gamma), granulocyte macrophage colony stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta). Treatment of BBM with rBoIFN-gamma, rBoGM-CSF or E. coli LPS resulted in decreased intracellular survival of H. somnus at 18 and 48 h, whereas BBM treated with rBoTNF-alpha or rBoIL-1beta had reduced intracellular survival of H. somnus only at 18 h. However, none of these treatments resulted in complete elimination of the intracellular bacteria. The ability of H. somnus to survive and multiply in both freshly isolated and cytokine-treated cultured BBM demonstrated the capability of H. somnus to escape from macrophage killing mechanisms. This capability may play a role in the dissemination of H. somnus infection in the body.

An efficient route to 2′-homouridine ( 1 ), a new nucleoside analogue, is reported that is based on an ene reaction. This nucleoside has been incorporated into a dinucleoside monophosphate and hydrolytic studies on the dimer show that it does not behave like a ribonucleotide.

A gene locus abp was identified immediately upstream of the CAMP factor gene cfu in Streptococcus uberis. An open reading frame capable of coding for a 277-residue protein was identified. On the basis of sequence characteristics, the abp gene product is potentially a polar amino acid and opine binding component of an ATP-binding cassette type (ABC-type) transport system similar to those of Gram-negative bacteria. This membrane protein is likely lipid modified at its amino terminus and was present in five S. uberis strains and one Streptococcus parauberis strain examined.Key words: bovine mastitis, Streptococcus uberis, amino acid transport.

N-Alkylated derivatives of pipecolic acid are shown to undergo highly stereoselective oxidation to give stable tertiary amine N-oxides. The ester derivatives show a high degree of stability compared to their proline analogues.

In an attempt to identify and characterize components of a heme uptake system of Haemophilus somnus, an Escherichia coli cosmid library of H. somnus genomic DNA was screened for the ability to bind hemin (Hmb+). The Hmb+ phenotype was associated with a 7,814-bp HindIII fragment of H. somnus DNA that was subcloned and sequenced. Thirteen open reading frames (orfs) were identified, all transcribed in one direction, and transposon mutagenesis identified orf7 as the gene associated with the Hmb+ phenotype. Orf7 (178 amino acids) has extensive homology with the lysozymes of bacteriophages P-A2, P21, P22, PZA, phi-29, phi-vML3, T4, or HP1. The orf7 gene complemented the lytic function of the K gene of phage P2 and the R gene of phage lambda. A lysozyme assay using supernatants from whole-cell lysates of E. coli cultures harboring plasmid pRAP501 or pGCH2 (both of which express the orf7 gene product) exhibited significant levels of lysozyme activity. The orf6 gene upstream of orf7 has the dual start motif common to the holins encoded by lambdoid S genes, and the orf6 gene product has significant homology to the holins of phages HP1 and P21. When expressed from a tac promoter, the orf6 gene product caused immediate cell death without lysis, while cultures expressing the orf7 gene product grew at normal rates but lysed immediately after the addition of chloroform. Based on this data, we concluded that the Hmb+ phenotype was an artifact resulting from the expression of cloned lysis genes which were detrimental to the E. coli host. The DNA flanking the cloned lysis genes contains orfs that are similar to structural and DNA packaging genes of phage P2. Polyclonal antiserum against Orf2, which is homologous to the major capsid precursor protein (gpN) of phage P2, detected a 40,000-M(r) protein expressed from pRAP401 but did not detect Orf2 in H. somnus, lysates. The phage-like DNA was detected in the serum-susceptible preputial strains HS-124P and HS-127P but was absent from the serum-resistant preputial strains HS-20P and HS-22P. Elucidation of a potential role for this cryptic prophage in the H. somnus life cycle requires more study.

Same-day images of the sodium and potassium atmospheres of Mercury were collected over a five-day period from December 6 to 10, 1990. Both sodium and potassium emissions were more intense at high latitudes and varied from day to day. The maximum emissions for sodium and potassium were strongly correlated with one another. These results support the view that sodium and potassium are both generated by the same process, namely sputtering of the surface at high latitudes by magnetospheric particles. The atmospheric abundance of potassium relative to sodium was less than previously observed. It is suggested that this resulted from more rapid removal of potassium from the atmosphere by photoionization during periods of high solar activity. Published by Elsevier Science Ltd

A telescope employing a liquid metal (mercury) mirror that is three meters in diameter was developed for the purpose of measuring the population of small orbital debris. The telescope is installed at a 9,000 ft site in the mountains of New Mexico at a latitude of 32.98 degrees, and has completed final optical performance tests. A Ford 2048 × 2048 CCD detector is used at the image plane. With this detector, the limiting stellar magnitude of the telescope was measured to be 23 at a S/N of about 3, with a nominal full width, half maximum for stellar images of 1.3 arcsec. Safety problems with toxic mercury vapor were minimal at operating temperatures below 60 F, greatly simplifying operations with the mirror. Performance of the telescope for debris at geosynchronous orbit (GEO) altitudes is estimated to be in the range 5 to 10 cm using the existing CCD detector. However, at its present location in New Mexico, the telescope cannot be used for detection of debris in the GEO region, since it cannot see debris with inclinations below 32 degrees. Performance of the telescope for debris in low earth orbit depends on the kind of detector that is used. Efforts were made to use the CCD detector for fast-moving low earth orbit debris by reading out the detector at the same rate and in the same direction as the debris object crosses the field of view of the telescope. In this mode, the telescope was capable of detecting debris as small as 3 centimeters at 900 km altitude. However, this mode is very inefficient, since debris moving in other directions is not detected. Observations have also been done using an intensified CCD video camera as the detector. The limiting detectable size for this detector was about 4 centimeters at 500 km, and 7 centimeters at 1000 km. A design was developed for the optimum detector for fast-moving debris in low earth orbit based on currently available technology. This is a 1024×1024 element CCD detector operating at 200 frames per second, with pixels binned to 16×16. This detector should be capable of detecting 1 cm debris at 500 km and 1.5 cm debris at 1000 km. New data processing algorithms will be required to process the data stream from this detector.

The majority of infections, including those caused by respiratory syncytial virus (RSV), occur at mucosal surfaces. As no RSV vaccine is available our goal is to produce an effective subunit vaccine with an adjuvant suitable for mucosal delivery and cross-presentation. A truncated secreted version of the RSV fusion (ΔF) protein formulated with polyI : C, an innate defence regulator peptide and polyphosphazene, induced local and systemic immunity, including affinity maturation of RSV F-specific IgG, IgA and virus-neutralizing antibodies, and F-specific CD8+ T-cells in the lung, when delivered intranasally. Furthermore, this ΔF protein formulation promoted the production of CD8+ central memory T-cells in the mediastinal lymph nodes and provided protection from RSV challenge. Formulation of ΔF protein with this adjuvant combination enhanced uptake by lung dendritic cells and trafficking to the draining lymph nodes. The ΔF protein formulation was confirmed to be highly efficacious and safe in cotton rats.

We propose a Josephson junction setup based on a topological insulator (TI) thin film to detect Majorana states, which exploits the unique helical and extended nature of the TI surface state. When the magnetic flux through the junction is close to an integer number of flux quanta, Majorana states, present on both surfaces of the film, give rise to a narrow peak-dip structure in the current- phase relation by hybridizing at the edge of the junction. Moreover, the maximal Majorana-state contribution to Josephson current takes a (nearly) universal value, approximately equal to the supercurrent capacity of a single quantum-channel. These features provide a characteristic signature of Majorana states based entirely on supercurrent., Comment: 6 pages, 5 figures

It is well known that the 3D electronic topological insulator (TI) with charge-conservation and time-reversal symmetry cannot have a trivial insulating surface that preserves symmetry. It is often implicitly assumed that if the TI surface preserves both symmetries then it must be gapless. Here we show that it is possible for the TI surface to be both gapped and symmetry-preserving, at the expense of having surface-topological order. In contrast to analogous bosonic topological insulators, this symmetric surface topological order is intrinsically non-Abelian. We show that the surface-topological order provides a complete non-perturbative definition of the electron TI that transcends a free-particle band-structure picture, and could provide a useful perspective for studying strongly correlated topological Mott insulators., Comment: 12 pages, 2 figures, (published version)

Prion diseases represent a novel form of infectivity caused by the propagated misfolding of a self-protein (PrP(C)) into a pathological, infectious conformation (PrP(Sc)). Efforts to develop a prion vaccine have been complicated by challenges and potential dangers associated with induction of strong immune responses to a self protein. There is considerable value in the development of vaccines that are specifically targeted to the misfolded conformation. Conformation specific immunotherapy depends on identification and optimization of disease-specific epitopes (DSEs)(1) that are uniquely exposed upon misfolding. Previously, we reported development of a PrP(Sc)-specific vaccine through empirical expansions of a YYR DSE. Here we describe optimization of two additional prion DSEs, YML of β-sheet 1 and a rigid loop (RL) linking β-sheet 2 to α-helix 2, through in silico predictions of B cell epitopes and further translation of these epitopes into PrP(Sc)-specific vaccines. The optimized YML and RL vaccines retain their properties of immunogenicity, specificity and safety when delivered individually or in a multivalent format. This investigation supports the utility of combining DSE prediction models with algorithms to infer logical peptide expansions to optimize immunogenicity. Incorporation of optimized DSEs into established vaccine formulation and delivery strategies enables rapid development of peptide-based vaccines for protein misfolding diseases.

Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders caused by misfolding of a cellular protein PrP(C) into an infectious conformation PrP(Sc). Previously our group demonstrated induction of PrP(Sc)-specific antibodies with a SN6b vaccine that targets regions of the protein that are exposed upon misfolding. There are concerns that these antibodies could function as templates to promote misfolding and cause disease. To evaluate the consequences of prolonged exposure to PrP(Sc)-specific antibodies in a prion sensitized animal, tga20 mice were vaccinated with the SN6b vaccine. No clinical signs of disease were detected up to 255 d post-vaccination, and postmortem assay of brains and spleens revealed no proteinase-K resistant PrP. These results suggest that vaccinating against TSEs with the SN6b antigen is safe from the standpoint of prion disease induction.

Compelling data supports the hypothesis that Pin1 inhibitors will be useful for the therapy of cancer: Pin1 deficient mice resist the induction of breast cancers normally evoked by expression of MMTV-driven Ras or Erb2 alleles. While Pin1 poses challenges for drug discovery, several groups have identified potent antagonists by structure based drug design, significant progress has been made designing peptidic inhibitors and a number of natural products have been found that blockade Pin1, notably epigallocatchechin gallate (EGCG), a major flavonoid in green tea. Here we critically discuss the modes of action and likely specificity of these compounds, concluding that a suitable chemical biology tool for probing the function of Pin1 has yet to be found. We conclude by outlining some open questions regarding the target validation of Pin1 and the prospects for identification of improved inhibitors in the future.

A fundamental open problem in condensed-matter physics is how the dichotomy between conventional and topological band insulators is modified in the presence of strong electron interactions. We show that there are six interacting electronic topological insulators that have no noninteracting counterpart. Combined with the previously known band insulators, these produce a total of eight topologically distinct phases. Two of the six interacting topological insulators can be described as Mott insulators in which the electron spins form spin analogs of the topological band insulator. The remaining phases are obtained as combinations of these two “topological paramagnets” and the topological band insulator. We prove that these eight phases form a complete list of all possible interacting topological insulators and discuss their experimental signatures., United States. Dept. of Energy (DESC-8739-ER46872), National Science Foundation (U.S.) (Grant ADGE-0801525), Simons Foundation (Award 229736)

Compelling data supports the hypothesis that Pin1 inhibitors will be useful for the therapy of cancer: Pin1 deficient mice resist the induction of breast cancers normally evoked by expression of MMTV-driven Ras or Erb2 alleles. While Pin1 poses challenges for drug discovery, several groups have identified potent antagonists by structure based drug design, significant progress has been made designing peptidic inhibitors and a number of natural products have been found that blockade Pin1, notably epigallocatchechin gallate (EGCG), a major flavonoid in green tea. Here we critically discuss the modes of action and likely specificity of these compounds, concluding that a suitable chemical biology tool for probing the function of Pin1 has yet to be found. We conclude by outlining some open questions regarding the target validation of Pin1 and the prospects for identification of improved inhibitors in the future.

In mean-field descriptions of nodal d-wave superconductors, generic edges exhibit dispersionless Majorana fermion bands at zero energy. These states give rise to an extensive ground-state degeneracy, and are protected by time-reversal symmetry. We argue that the infinite density of states of these flat bands make them inherently unstable to interactions, and show that repulsive interactions lead to edge ferromagnetism which splits the flat bands. This edge ferromagnetism offers an explanation for the observation of the splitting of zero-bias peaks in edge tunneling in high-Tc cuprate superconductors. We argue that this mechanism for splitting is more likely than previously proposed scenarios and describe its experimental consequences.

Stereotactic radiosurgery (SRS) is a well established, minimally invasive treatment option for patients diagnosed with cerebral arteriovenous malformations (AVM). We present the experience in linear accelerator-based SRS for cerebral AVM treated over 14 years. We prospectively followed 67 patients with 69 AVM treated with SRS from 1994 to 2008, inclusive. The mean patient age was 37 years (range 7-69) with 36 women and 31 men. The median AVM size, as defined by maximal diameter, was 2.5 cm (range 0.5-4.6 cm) and the median marginal dose was 18 Gy in one fraction. The crude angiographic obliteration rate was 55% with a 3 and 5 year actuarial rate of 39% and 65%, respectively. Median time to obliteration was 4.2 years. Higher treatment dose (p0.0001) and smaller maximal AVM diameter (p=0.002) were associated with an increased obliteration rate. There were no deaths from treatment. Post-treatment neurological complications occurred in 10 patients (15%) including hemorrhage in two. Twelve patients (18%) required a second SRS procedure. Larger AVM diameter was associated with increased odds of requiring re-treatment (p=0.02). Radiosurgery for intracerebral AVM is a non-invasive therapeutic option with low morbidity and a reasonable likelihood of nidus obliteration. Treatment dose and AVM diameter are the main determinants of obliteration.

The practice of immunization of animals and humans has been carried out for centuries and is generally accepted as the most cost effective and sustainable method of infectious disease control. Over the past 20 years there have been significant changes in our ability to produce antigens by conventional extraction and purification, recombinant DNA and synthesis. However, many of these products need to be combined with carrier molecules to generate optimal immune responses. This review covers selected topics in the development of carrier technologies for use in the veterinary vaccine field, including glycoconjugate and peptide vaccines, microparticle and nanoparticle formulations, and finally virus-like particles. © 2012.