Virus Sharing, Genetic Sequencing, and Global Health Security

The WHO’s Pandemic Influenza Preparedness (PIP) Framework was a milestone global agreement designed to promote the international sharing of biological samples to develop vaccines, while that ensuring poorer countries would have access to those vaccines. Since the PIP Framework was negotiated, scientists have developed the capacity to use genetic sequencing data (GSD) to develop synthetic viruses rapidly for product development of life-saving technologies in a time-sensitive global emergency—threatening to unravel the Framework. Access to GSD may also have major implications for biosecurity, biosafety, and intellectual property (IP). By rendering the physical transfer of viruses antiquated, GSD may also undermine the effectiveness of the PIP Framework itself, with disproportionate impacts on poorer countries. We examine the changes that need to be made to the PIP Framework to address the growing likelihood that GSD might be shared instead of physical virus samples. We also propose that the international community harness this opportunity to expand the scope of the PIP Framework beyond only influenza viruses with pandemic potential. In light of non-influenza pandemic threats such as the Middle East Respiratory Syndrome (MERS) and Ebola, we call for an international agreement on the sharing of the benefits of research – such as vaccines and treatments – for other infectious diseases to ensure not only a more secure and healthy world, but also a more just world, for humanity

High prevalence of scrapie in a dairy goat herd: tissue distribution of disease-associated PrP and effect of PRNP genotype and age

Following a severe outbreak of clinical scrapie in 2006–2007, a large dairy goat herd was culled and 200 animals were selected for post-mortem examinations in order to ascertain the prevalence of infection, the effect of age, breed and PRNP genotype on the susceptibility to scrapie, the tissue distribution of diseaseassociated PrP (PrP$^{\rm d}$), and the comparative efficiency of different diagnostic methods. As determined by immunohistochemical (IHC) examinations with Bar224 PrP antibody, the prevalence of preclinical infection was very high (72/200; 36.0%), with most infected animals being positive for PrP$^{\rm d}$ in lymphoreticular system (LRS) tissues (68/72; 94.4%) compared to those that were positive in brain samples (38/72; 52.8%). The retropharyngeal lymph node and the palatine tonsil showed the highest frequency of PrP$^{\rm d}$ accumulation (87.3% and 84.5%, respectively), while the recto-anal mucosa-associated lymphoid tissue (RAMALT) was positive in only 30 (41.7%) of the infected goats. However, the efficiency of rectal and palatine tonsil biopsies taken shortly before necropsy was similar. The probability of brain and RAMALT being positive directly correlated with the spread of PrP$^{\rm d}$ within the LRS. The prevalence of infection was influenced by PRNP genetics at codon 142 and by the age of the goats: methionine carriers older than 60 months showed a much lower prevalence of infection (12/78; 15.4%) than those younger than 60 months (20/42; 47.6%); these last showed prevalence values similar to isoleucine homozygotes of any age (40/80; 50.0%). Two of seven goats with definite signs of scrapie were negative for PrP$^{\rm d}$ in brain but positive in LRS tissues, and one goat showed biochemical and IHC features of PrP$^{\rm d}$ different from all other infected goats. The results of this study have implications for surveillance and control policies for scrapie in goats

Internal Disinhibition Predicts Weight Regain Following Weight Loss and Weight Loss Maintenance

Objective: The disinhibition scale of the Eating Inventory predicts weight loss outcome; however, it may include multiple factors. The purpose of this study was to examine the factor structure of the disinhibition scale and determine how its factors independently relate to long-term weight loss outcomes. Research Methods and Procedures: Exploratory factor analysis of the disinhibition scale was conducted on 286 participants in a behavioral weight loss trial (TRIM), and confirmatory factor analysis was conducted on 3345 members of the National Weight Control Registry (NWCR), a registry of successful weight loss maintainers. Multivariate regressions were used to examine the relationships between the disinhibition scale factors and weight over time in both samples. Results: Using baseline data from TRIM, two factors were extracted from the disinhibition scale: 1) an internal factor that described eating in response to internal cues, such as feelings and thoughts; and 2) an external factor that described eating in response to external cues, such as social events. This factor structure was confirmed using confirmatory factor analysis in the NWCR. In TRIM, internal disinhibition significantly predicted weight loss at 6 months (p = 0.03) and marginally significantly predicted weight loss at 18 months (p = 0.06), with higher levels of internal disinhibition at baseline predicting less weight loss; external disinhibition did not predict weight loss at any time-point. In NWCR, internal disinhibition significantly predicted one-year weight change (p = 0.001), while external disinhibition did not. Discussion: These results suggest that it is the disinhibition of eating in response to internal cues that is associated with poorer long-term weight loss outcomes

Field-dependent heat transport in the Kondo insulator SmB6 : phonons scattered by magnetic impurities

The thermal conductivity $\kappa$ of the Kondo insulator SmB$_6$ was measured at low temperature, down to 70 mK, in magnetic fields up to 15 T, on single crystals grown using both the floating-zone and the flux methods. The residual linear term $\kappa_0/T$ at $T \to 0$ is found to be zero in all samples, for all magnetic fields, in agreement with previous studies. There is therefore no clear evidence of fermionic heat carriers. In contrast to some prior data, we observe a large enhancement of $\kappa(T)$ with increasing field. The effect of field is anisotropic, depending on the relative orientation of field and heat current (parallel or perpendicular), and with respect to the cubic crystal structure. We interpret our data in terms of heat transport predominantly by phonons, which are scattered by magnetic impurities.Comment: publish versio

Modelling lubricated revolute joints in multibody mechanical systems

This work deals with the modelling of lubricated revolute joints in multibody mechanical systems. In most machines and mechanisms, the joints are designed to operate with some lubricant fluid. The high pressures generated in the lubricant fluid act to keep the journal and the bearing apart. Moreover, the thin film formed by lubricant reduces friction and wear, provides load capacity and adds damping to dissipate undesirable mechanical vibrations. In the dynamic analysis of journal–bearings, the hydrodynamic forces, which include both squeeze and wedge effects, produced by the lubricant fluid oppose the journal motion. These forces are obtained by integrating the pressure distribution evaluated with the aid of Reynolds’ equation written for the dynamic regime. The hydrodynamic forces are nonlinear functions of journal centre position and velocity relative to the bearing centre. In a simple way, the hydrodynamic forces built up by the lubricant fluid are evaluated from the state of variable of the system and included into the equations of motion of the mechanical system. Results for an elementary slider–crank mechanism, in which a lubricated revolute joint connects the connecting rod and slider, are used to discuss the assumptions and procedures adopted.Fundação para a Ciência e a Tecnologia (FCT

Use of the polymerase chain reaction for screening and evaluation of recombinant baculovirus clones

We report the application of the PCR for screening and high-resolution characterization of recombinant baculovirus clones. Starting with less than 10 nanograms of viral DNA, it is possible to 1) demonstrate that the DNA sequence to be expressed has not been deleted or rearranged during the co-transfection or homologous recombination events, 2) test for the presence of wild-type virus in the isolate and 3) generate amplified DNA that can be used for nucleotide sequence analysis or high-resolution restriction analysis. The method is based upon PCR of genomic viral DNA prepared from primary amplified stocks of extracellular virus using a small-scale procedure. The approach has special relevance for definitive characterization of recombinant virus used to express point mutant proteins and for characterization of recombinant virus generated through use of mixed oligonucleotides or random mutagenesis

Incommensurate magnetism near quantum criticality in CeNiAsO

Two phase transitions in the tetragonal strongly correlated electron system CeNiAsO were probed by neutron scattering and zero field muon spin rotation. For $T <T_{N1}$ = 8.7(3) K, a second order phase transition yields an incommensurate spin density wave with wave vector $\textbf{k} = (0.44(4), 0, 0)$. For $T < T_{N2}$ = 7.6(3) K, we find co-planar commensurate order with a moment of $0.37(5)~\mu_B$, reduced to $30 \%$ of the saturation moment of the $|\pm\frac{1}{2}\rangle$ Kramers doublet ground state, which we establish by inelastic neutron scattering. Muon spin rotation in $\rm CeNiAs_{1-x}P_xO$ shows the commensurate order only exists for x $\le$ 0.1 so the transition at $x_c$ = 0.4(1) is from an incommensurate longitudinal spin density wave to a paramagnetic Fermi liquid