Polymeric Adjuvants for Vaccine Delivery

This research has investigated the use of pentablock copolymers and polyanhydride nanoparticles in combination to form a hydrogel matrix giving controlled and sustained release of model protein ovalbumin (OVA) for vaccine delivery applications. To investigate the influence of hydrogel composition on release of OVA, the weight percent of polyvinyl alcohol (PVA), form of OVA, and molecular weight of pentablock copolymer were varied. The weight percent of PVA was tested for 20% and 30%. Molecular weight of the pentablock copolymer was also varied giving a low molecular weight or high molecular weight copolymer. Lastly, OVA was incorporated into hydrogels either in a free form, encapsulated in polyanhydride nanoparticles, or a combination of the two. For all trials, the total OVA amount loaded was constant, and release curves of protein with time were observed for 4 days. Overall, these release curves confirmed gradual and controlled release of OVA. They also showed that the amount of OVA released from 20% PVA hydrogels was greater than the protein released from 30% hydrogels due to structural differences of the matrices. Lastly, the encapsulated OVA versus free OVA influenced total protein amount released and varied with % PVA and molecular weight of copolymer

Impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes of liver disease

Chronic infections with the hepatitis B and C viruses have significant worldwide health and economic impacts. Previous treatments for hepatitis C such as interferon and ribavirin therapy were ineffective and poorly tolerated by patients. The introduction of directly acting curative antiviral therapy for hepatitis C and the wider use of nucleos(t)ide analogues for suppression of chronic Hepatitis B infection have resulted in many positive developments. Decreasing the prevalence of hepatitis B and C have concurrently reduced transmission rates and hence, the number of new infections. Antiviral treatments have decreased the rates of liver decompensation and as a result, lowered hospitalisation and mortality rates for both chronic hepatitis B and C infection. The quality of life of chronically infected patients has also been improved significantly by modern treatment. Antiviral therapy has stopped the progression of liver disease to cirrhosis in certain patient cohorts and prevented ongoing hepatocellular damage in patients with existing cirrhosis. Longer term benefits of antiviral therapy include a reduced risk of developing hepatocellular carcinoma and decreased number of patients requiring liver transplantation. This review article assesses the literature and summarises the impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes from liver disease

Hackney: a cycling borough for whom?

London’s internationally acclaimed “cycling revolution” was characterised by an unprecedented investment in cycling infrastructure, particularly cycle lanes manifesting as Cycle Superhighways or Quietways. Despite the hegemony of cycle lanes in London’s overarching cycling paradigm, the London Borough of Hackney has historically achieved the city’s highest rates of cycling and a long-standing reputation as a cycling borough in the absence of cycle lanes. Instead, Hackney has always opted for spatial interventions (such as filtered permeability, a borough-wide 20 mph speed restriction, and speed humps). This paper challenges Hackney’s reputation as a cycling borough and the alleged success of its spatial interventions. I argue that Hackney’s privileging of spatial fixes treats spatial interventions as apolitical and value-neutral, which ignores inequities entrenched in cycling. I also argue that Hackney has taken for granted its high rates of cycling, therefore effectively adopting a cycle-blind (akin to race-blind) and cycle mainstreaming (akin to gender mainstreaming) approach to cycling policy and interventions. Consequently, Hackney’s spatial interventions for cycling raise the profile of already-visible privileged cyclists (white, middle-class men – the middle-aged men in Lycra, or MAMILs, and the hipsters) for whom cycling is a lifestyle choice while further erasing “invisible cyclists” for whom cycling is an economic necessity. In order to be a relevant and sustainable mode of transportation for Hackney residents, equity and social justice must foreground the borough’s approach to cycling

Polarization Aberration in Astronomical Telescopes

The point spread function (PSF) for astronomical telescopes and instruments depends not only on geometric aberrations and scalar wave diffraction, but also on the apodization and wavefront errors introduced by coatings on reflecting and transmitting surfaces within the optical system. The functional form of these aberrations, called polarization aberrations, result from the angles of incidence and the variations of the coatings as a function of angle. These coatings induce small modifications to the PSF, which consists of four separate components, two nearly Airy-disk PSF components, and two faint components, we call ghost PSF components, with a spatial extent about twice the size of the diffraction limited image. As the specifications of optical systems constantly improve, these small effects become increasingly important. It is shown how the magnitude of these ghost PSF components, at ~10^(-5) in the example telescope, can interfere with exoplanet detection with coronagraphs

The Influence of Signaling Conspecific and Heterospecific Neighbors on Eavesdropper Pressure

The study of tradeoffs between the attraction of mates and the attraction of eavesdropping predators and parasites has generally focused on a single species of prey, signaling in isolation. In nature, however, animals often signal from mixed-species aggregations, where interactions with heterospecific group members may be an important mechanism modulating tradeoffs between sexual and natural selection, and thus driving signal evolution. Although studies have shown that conspecific signalers can influence eavesdropper pressure on mating signals, the effects of signaling heterospecifics on eavesdropper pressure, and on the balance between natural and sexual selection, are likely to be different. Here, we review the role of neighboring signalers in mediating changes in eavesdropper pressure, and present a simple model that explores how selection imposed by eavesdropping enemies varies as a function of a signaling aggregation\u27s species composition, the attractiveness of aggregation members to eavesdroppers, and the eavesdroppers\u27 preferences for different member types. This approach can be used to model mixed-species signaling aggregations, as well as same-species aggregations, including those with non-signaling individuals, such as satellites or females. We discuss the implications of our model for the evolution of signal structure, signaling behavior, mixed-species aggregations, and community dynamics

The influence of signaling conspecific and heterospecific neighbors on eavesdropper pressure

Sherpa Romeo green journal. Open access article. Creative Commons Attribution License (CC BY) applies.The study of tradeoffs between the attraction of mates and the attraction of eavesdropping predators and parasites has generally focused on a single species of prey, signaling in isolation. In nature, however, animals often signal from mixed-species aggregations, where interactions with heterospecific group members may be an important mechanism modulating tradeoffs between sexual and natural selection, and thus driving signal evolution. Although studies have shown that conspecific signalers can influence eavesdropper pressure on mating signals, the effects of signaling heterospecifics on eavesdropper pressure, and on the balance between natural and sexual selection, are likely to be different. Here, we review the role of neighboring signalers in mediating changes in eavesdropper pressure, and present a simple model that explores how selection imposed by eavesdropping enemies varies as a function of a signaling aggregation’s species composition, the attractiveness of aggregation members to eavesdroppers, and the eavesdroppers’ preferences for different member types. This approach can be used to model mixed-species signaling aggregations, as well as same-species aggregations, including those with non-signaling individuals, such as satellites or females. We discuss the implications of our model for the evolution of signal structure, signaling behavior, mixed-species aggregations, and community dynamics.Ye

Structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.

Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific γ-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8 Å resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-γ-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and γ-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-γ-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site

The predictive value of G8 and the Cancer and aging research group chemotherapy toxicity tool in treatment-related toxicity in older Chinese patients with cancer

Introduction: Older patients experience a higher risk of treatment-related toxicity (TRT). The G8 screening tool was developed to separate cancer older patients fit to receive standard treatment from those who are frail and experiencing functional decline due to reduced organ function and multiple comorbidities. The Cancer and Aging Research Group chemotherapy toxicity tool (CARG-tt) questionnaire was developed to predict chemotherapy toxicity in geriatric patients. This prospective observational study evaluated the performance of G8 and CARG-tt in predicting severe TRT in older Chinese cancer patients. Methods: Chinese patients aged ≥65 with a diagnosis of solid malignancy and scheduled to receive anti-cancer treatment (chemotherapy or targeted therapy) were enrolled from March 2016 to July 2017 at the Department of Clinical Oncology at Queen Mary Hospital in Hong Kong. All patients completed the G8 and CARG-tt screening and pre-treatment assessments before starting treatment. Patients were monitored for any severe TRT, which was defined by grades 3–5 using the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.03, treatment discontinuation, or unexpected hospitalization from starting to 30 days after treatment. Results: A total of 259 patients (male: 154, 59.5%; median age: 73.4, age range: 65–93) were enrolled in the study. Two hundred and ten (81.1%) patients received chemotherapy while the rest (n = 49, 18.9%) received targeted therapy. Overall, 146 patients (56.8%) experienced severe TRT. The mean G8 score was 12.4 (SD: 2.8). The G8 score had a significant association with unexpected admission (cutoff: 14, 41.3% vs. 26.5%, p = 0.03) but not significant in other types of TRTs. The mean CARG-tt score was 7.67 (SD: 3.7); it was not associated with severe TRTs. Conclusions: The G8 and CARG-tt demonstrated a weak prediction of severe TRT in older Chinese cancer patients. Future studies need to develop predictive tools for TRT in patients receiving novel antineoplastic therapies, with a focus on subgroup analysis for different populations

Abundance measurements of H₂O and carbon-bearing species in the atmosphere of WASP-127b confirm its super-solar metallicity

The chemical abundances of exoplanet atmospheres may provide valuable information about the bulk compositions, formation pathways, and evolutionary histories of planets. Exoplanets with large, relatively cloud-free atmospheres, and which orbit bright stars provide the best opportunities for accurate abundance measurements. For this reason, we measured the transmission spectrum of the bright (V∼10.2), large ($1.37 R_J$), sub-Saturn mass ($0.19 M_J$) exoplanet WASP-127b across the near-UV to near-infrared wavelength range (0.3–5 μm), using the Hubble and Spitzer Space Telescopes. Our results show a feature-rich transmission spectrum, with absorption from Na, $H_2O$, and $CO_2$, and wavelength-dependent scattering from small-particle condensates. We ran two types of atmospheric retrieval models: one enforcing chemical equilibrium, and the other which fit the abundances freely. Our retrieved abundances at chemical equilibrium for Na, O and C are all super-solar, with abundances relative to solar values of $9^{+15}_{-6}$, $16^{+7}_{-5}$⁠, and $26^{+12}_{-9}$ respectively. Despite giving conflicting C/O ratios, both retrievals gave super-solar $CO_2$ volume mixing ratios, which adds to the likelihood that WASP-127b’s bulk metallicity is super-solar, since $CO_2$ abundance is highly sensitive to atmospheric metallicity. We detect water at a significance of 13.7 σ. Our detection of Na is in agreement with previous ground-based detections, though we find a much lower abundance, and we also do not find evidence for Li or K despite increased sensitivity. In the future, spectroscopy with JWST will be able to constrain WASP-127b’s C/O ratio, and may reveal the formation history of this metal-enriched, highly observable exoplanet