Two Influenza A Virus-Specific Fabs Neutralize by Inhibiting Virus Attachment to Target Cells, While Neutralization by Their IgGs Is Complex and Occurs Simultaneously through Fusion Inhibition and Attachment Inhibition

AbstractMabs H36 (IgG2a) and H37 (IgG3) recognize epitopes in antigenic sites Sb and Ca2, respectively, in the HA1 subunit of influenza virus A/PR/8/34 (H1N1). Their neutralization was complex. Our aim here was to investigate the mechanism of neutralization by the IgGs and their Fabs. In MDCK and BHK cells, both IgGs neutralized primarily by inhibiting virus–cell fusion, although at higher IgG concentrations virus attachment to target cells was also inhibited. In contrast, the Fabs neutralized entirely by inhibiting virus attachment, although a higher concentration of Fab than IgG was required to bring this about. Both H36 and H37 exerted a concentration-dependent spectrum of neutralization activity, with virus–cell fusion inhibition and virus–cell attachment inhibition being the predominant mechanisms at low- and high-antibody concentration, respectively, and both mechanisms occurring simultaneously at intermediate concentrations. However, it may be that attachment inhibition was a secondary event, occurring to virus that had already been neutralized through inhibition of its fusion activity. Neutralization by H36 and H37 Fabs was a simple process. Both inhibited virus attachment but required much higher (>100-fold) molar concentrations for activity than did IgG. The functional affinities of the IgGs were high (0.4–0.6 nM) and differences between these and the affinity of their Fabs (H36, nil; H37, 23-fold) were not sufficient to explain the differences observed in neutralization. Similar neutralization data were obtained in two different cell lines. The dose–response curve for neutralization by H36 F(ab′)2 resembled that for IgG, although eightfold more F(ab′)2 was required for 50% neutralization. Overall, neutralization mechanisms of H36 and H37 antibodies were similar, and thus independent of antigenic site, antibody isotype, and target cell

Exercise training and resting blood pressure: a large-scale pairwise and network meta-analysis of randomised controlled trials

Objective: To perform a large-scale pairwise and network meta-analysis on the effects of all relevant exercise training modes on resting blood pressure to establish optimal anti-hypertensive exercise prescription practices. Design: Systematic review and network meta-analysis. Data sources: PubMed (MEDLINE), the Cochrane library and Web of Science were systematically searched. Eligibility criteria: Randomised controlled trials published between 1990 and February 2023. All relevant work reporting systolic blood pressure (sBP) and/or diastolic (dBP) reductions following an exercise intervention ≥2 weeks with an eligible non-intervention control group were included. Results: 270 randomised controlled trials were ultimately included in the final analysis, with a pooled sample size of 15,827 participants. Pairwise analyses demonstrated significant reductions in resting sBP and dBP following aerobic exercise training (-4.49/-2.53mmHg, P<0.001), dynamic resistance training (-4.55/-3.04mmHg, P<0.001), combined training (-6.04/-2.54mmHg, P<0.001), high intensity interval training (-4.08/-2.50mmHg, P<0.001) and isometric exercise training (-8.24/-4.00mmHg, P<0.001). As evidenced in the network meta-analysis, the rank order of effectiveness based on the surface under the cumulative ranking curve (SUCRA) values for sBP were isometric exercise training (SUCRA: 98.3%), combined training (75.7%), dynamic resistance training (46.1%), aerobic exercise training (40.5%) and high intensity interval training (39.4%). Secondary network meta-analyses revealed isometric wall squat and running as the most effective sub-modes for reducing sBP (90.4%) and dBP (91.3%) respectively. Conclusion: Various exercise training modes improve resting blood pressure, particularly isometric exercise. The results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension

Seismic data reveal eastern Black Sea Basin structure

Rifted continental margins are formed by progressive extension of the lithosphere. The development of these margins plays an integral role in the plate tectonic cycle, and an understanding of the extensional process underpins much hydrocarbon exploration. A key issue is whether the lithosphere extends uniformly, or whether extension varies\ud with depth. Crustal extension may be determined using seismic techniques. Lithospheric extension may be inferred from the waterloaded subsidence history, determined from\ud the pattern of sedimentation during and after rifting. Unfortunately, however, many rifted margins are sediment-starved, so the subsidence history is poorly known.\ud To test whether extension varies between the crust and the mantle, a major seismic experiment was conducted in February–March 2005 in the eastern Black Sea Basin (Figure 1), a deep basin where the subsidence history is recorded\ud by a thick, post-rift sedimentary sequence. The seismic data from the experiment indicate the presence of a thick, low-velocity zone, possibly representing overpressured sediments. They also indicate that the basement and\ud Moho in the center of the basin are both several kilometers shallower than previously inferred. These initial observations may have considerable impact on thermal models of the petroleum system in the basin. Understanding\ud the thermal history of potential source rocks is key to reducing hydrocarbon exploration risk. The experiment, which involved collaboration between university groups in the United Kingdom, Ireland, and Turkey, and BP and\ud Turkish Petroleum (TPAO), formed part of a larger project that also is using deep seismic reflection and other geophysical data held by the industry partners to determine the subsidence history and hence the strain evolution of\ud the basin

Cluster Spin Glass Distribution Functions in La2−x_{2-x}Srx_xCuO4_4

Signatures of the cluster spin glass have been found in a variety of experiments, with an effective onset temperature $T_{on}$ that is frequency dependent. We reanalyze the experimental results and find that they are characterized by a distribution of activation energies, with a nonzero glass transition temperature $T_g(x)<T_{on}$. While the distribution of activation energies is the same, the distribution of weights depends on the process. Remarkably, the weights are essentially doping independent.Comment: 5 pages, 5 ps figure

Heterotic compactifications on SU(2)-structure backgrounds

In this paper we study the reduction of heterotic string theory on SU(2)-structure backgrounds. We compute the bosonic low-energy gauged N=2 supergravity specified by the Killing vectors corresponding to the gauged isometries. We check that the obtained Lagrangian is consistent with the one of N=2 local supersymmetry. We also determine the Killing prepotentials.Comment: reference added, corrected typos and some factor

Combining a ractopamine feeding regime and porcine somatotropin has additive effects on finisher pig performance

Treatment of finisher pigs with dietary ractopamine (RAC; Paylean®, Elanco Animal Health, NSW) improves daily gain and feed efficiency commensurate with increased protein deposition in finishing pigs (Dunshea et al., 1993). However, effects of RAC on P2 fat deposition are equivocal. Dunshea et al. (1993) found no change in gilts and barrows, whilst a trend towards reduced P2 depth was observed in boars fed dietary RAC. Exogenous porcine somatotropin (pST; Reporcin®, OzBioPharm Pty Ltd, Victoria) improves daily gain and feed efficiency and increases the ratio oflean to fat in carcases of boars, gilts and barrows (Campbell et al., 1989). As both technologies are applied at the end of the finishing phase, it is of interest to determine whether a combination of RAC and pST has additive effects on pig performance

Diffusion-Weighted MRI: Distinction of Skull Base Chordoma from Chondrosarcoma

BACKGROUND AND PURPOSE: Chordoma and chondrosarcoma of the skull base are rare tumors with overlapping presentations and anatomic imaging features but different prognoses. We hypothesized that these tumors might be distinguished by using diffusion-weighted MR imaging. MATERIALS AND METHODS: We retrospectively reviewed 19 patients with pathologically confirmed chordoma or chondrosarcoma who underwent both conventional and diffusion-weighted MR imaging. Differences in distributions of ADC were assessed by the Kruskal-Wallis test. Associations between histopathologic diagnosis and conventional MR imaging features (T2 signal intensity, contrast enhancement, and tumor location) were assessed with the Fisher exact test. RESULTS: Chondrosarcoma was associated with the highest mean ADC value (2051 ± 261 × 10−6 mm2/s) and was significantly different from classic chordoma (1474 ± 117 × 10−6 mm2/s) and poorly differentiated chordoma (875 ± 100 × 10−6 mm2/s) (P CONCLUSIONS: Diffusion-weighted MR imaging may be useful in assessing clival tumors, particularly in differentiating chordoma from chondrosarcoma. A prospective study of a larger cohort will be required to determine the value of ADC in predicting histopathologic diagnosis

Statistical Model of Superconductivity in a 2D Binary Boson-Fermion Mixture

A two-dimensional (2D) assembly of noninteracting, temperature-dependent, composite-boson Cooper pairs (CPs) in chemical and thermal equilibrium with unpaired fermions is examined in a binary boson-fermion statistical model as the superconducting singularity temperature is approached from above. The model is derived from {\it first principles} for the BCS model interfermion interaction from three extrema of the system Helmholtz free energy (subject to constant pairable-fermion number) with respect to: a) the pairable-fermion distribution function; b) the number of excited (bosonic) CPs, i.e., with nonzero total momenta--usually ignored in BCS theory--and with the appropriate (linear, as opposed to quadratic) dispersion relation that arises from the Fermi sea; and c) the number of CPs with zero total momenta. Compared with the BCS theory condensate, higher singularity temperatures for the Bose-Einstein condensate are obtained in the binary boson-fermion mixture model which are in rough agreement with empirical critical temperatures for quasi-2D superconductorsComment: 16 pages and 4 figures. This is a improved versio

Increasing ractopamine levels in finisher pig diets improves growth performance in light, medium and heavy boars

The objective of this study was to determine the dose response to RAC in light, medium and heavy-weight boars

Type II compactifications on manifolds with SU(2) x SU(2) structure

We study compactifications of type II theories on SU(2) x SU(2) structure manifolds to six, five and four spacetime dimensions. We use the framework of generalized geometry to describe the NS-NS sector of such compactifications and derive the structure of their moduli spaces. We show that in contrast to SU(3) x SU(3) structure compactifications, there is no dynamical SU(2) x SU(2) structure interpolating between an SU(2) structure and an identity structure. Furthermore, we formulate type II compactifications on SU(2) x SU(2) structures in the context of exceptional generalized geometry which makes the U-duality group manifest and naturally incorporates the scalar degrees of freedom arising in the Ramond-Ramond sector. Via this formalism we derive the structure of the moduli spaces as it is expected from N=4 supergravity.Comment: 69 pages, v2 published versio