The Aqueous and Acetonitrile Bond Dissociation Free Energies of -Hydroxyphthalimide.

Widely cited values of 89 and 90.9 kcal/mol for the bond-dissociation free energy of -hydroxyphthalimide (NHPI) in water and acetonitrile, respectively, are in error. The sources of the errors leading to these values have been explored and corrected.

A Glycolipid-Peptide-Hapten Tricomponent Conjugate Vaccine Generates Durable Antihapten Antibody Responses in Mice.

Eliciting an antihapten antibody response to vaccination typically requires the use of constructs where multiple copies of the hapten are covalently attached to a larger carrier molecule. The carrier is required to elicit T cell help via presentation of peptide epitopes on major histocompatibility complex (MHC) class II molecules; as such, attachment to full-sized proteins, alone or in a complex, is generally used to account for the significant MHC diversity in humans. While such carrier-based vaccines have proven extremely successful, particularly in protecting against bacterial diseases, they can be challenging to manufacture, and repeated use can be compromised by pre-existing immunity against the carrier.

Preclinical evaluation of therapeutic vaccines for chronic hepatitis B that stimulate antiviral activities of T cells and NKT cells.

Background & Aims: Liver diseases resulting from chronic HBV infection are a significant cause of morbidity and mortality. Vaccines that elicit T-cell responses capable of controlling the virus represent a treatment strategy with potential for long-term effects. Here, we evaluated vaccines that induce the activity of type I natural killer T (NKT) cells to limit viral replication and license stimulation of conventional antiviral T-cells.

Tumor-targeted therapy with BRAF-inhibitor recruits activated dendritic cells to promote tumor immunity in melanoma.

Background: Tumor-targeted therapy causes impressive tumor regression, but the emergence of resistance limits long-term survival benefits in patients. Little information is available on the role of the myeloid cell network, especially dendritic cells (DC) during tumor-targeted therapy.

Methods: Here, we investigated therapy-mediated immunological alterations in the tumor microenvironment (TME) and tumor-draining lymph nodes (LN) in the D4M.

Exploring the Impact of Active Site Structure on the Conversion of Methane to Methanol in Cu-Exchanged Zeolites.

In the past, Cu-oxo or -hydroxy clusters hosted in zeolites have been suggested to enable the selective conversion of methane to methanol, but the impact of the active site's stoichiometry and structure on methanol production is still poorly understood. Herein, we apply theoretical modeling in conjunction with experiments to study the impact of these two factors on partial methane oxidation in the Cu-exchanged zeolite SSZ-13. Phase diagrams developed from first-principles suggest that Cu-hydroxy or Cu-oxo dimers are stabilized when O or NO are used to activate the catalyst, respectively.

Recruiting Natural Killer T Cells to Improve Vaccination: Lessons from Preclinical and Clinical Studies.

The capacity of type I natural killer T (NKT) cells to provide stimulatory signals to antigen-presenting cells has prompted preclinical research into the use of agonists as immune adjuvants, with much of this work focussed on stimulating T cell responses to cancer. In attempting to evaluate this approach in the clinic, our recent dendritic-cell based study failed to show an advantage to adding an agonist to the vaccine. Here we present potential limitations of the study, and suggest why other simpler strategies may be more effective.

Control over Charge Separation by Imine Structural Isomerization in Covalent Organic Frameworks with Implications on CO Photoreduction.

Two-dimensional covalent organic frameworks (COFs) are an emerging class of photocatalytic materials for solar energy conversion. In this work, we report a pair of structurally isomeric COFs with reversed imine bond directions, which leads to drastic differences in their physical properties, photophysical behaviors, and photocatalytic CO reduction performance after incorporating a Re(bpy)(CO)Cl molecular catalyst through bipyridyl units on the COF backbone (Re-COF). Using the combination of ultrafast spectroscopy and theory, we attributed these differences to the polarized nature of the imine bond that imparts a preferential direction to intramolecular charge transfer (ICT) upon photoexcitation, where the bipyridyl unit acts as an electron acceptor in the forward imine case (f-COF) and as an electron donor in the reverse imine case (r-COF).

Tracking Active Phase Behavior on Boron Nitride during the Oxidative Dehydrogenation of Propane Using Operando X-ray Raman Spectroscopy.

Hexagonal boron nitride (hBN) is a highly selective catalyst for the oxidative dehydrogenation of propane (ODHP) to propylene. Using a variety of characterization techniques, the activity of the catalyst has been attributed to the formation of an amorphous boron oxyhydroxide surface layer. The ODHP reaction mechanism proceeds via a combination of surface mediated and gas phase propagated radical reactions with the relative importance of both depending on the surface-to-void-volume ratio.

Doxapram versus placebo in preterm newborns: a study protocol for an international double blinded multicentre randomized controlled trial (DOXA-trial).

Background: Apnoea of prematurity (AOP) is one of the most common diagnoses among preterm infants. AOP often leads to hypoxemia and bradycardia which are associated with an increased risk of death or disability. In addition to caffeine therapy and non-invasive respiratory support, doxapram might be used to reduce hypoxemic episodes and the need for invasive mechanical ventilation in preterm infants, thereby possibly improving their long-term outcome.

Off-Stoichiometric Restructuring and Sliding Dynamics of Hexagonal Boron Nitride Edges in Conditions of Oxidative Dehydrogenation of Propane.

Boron-containing materials, such as hexagonal boron nitride (h-BN), recently shown to be active and selective catalysts for the oxidative dehydrogenation of propane (ODHP), have been shown to undergo significant surface oxyfunctionalization and restructuring. Although experimental ex situ studies have probed the change in chemical environment on the surface, the structural evolution of it under varying reaction conditions has not been established. Herein, we perform global optimization structure search with a grand canonical genetic algorithm to explore the chemical space of off-stoichiometric restructuring of the h-BN surface under ambient as well as ODHP-relevant conditions.

mRNA vaccine against malaria tailored for liver-resident memory T cells.

Malaria is caused by Plasmodium species transmitted by Anopheles mosquitoes. Following a mosquito bite, Plasmodium sporozoites migrate from skin to liver, where extensive replication occurs, emerging later as merozoites that can infect red blood cells and cause symptoms of disease. As liver tissue-resident memory T cells (Trm cells) have recently been shown to control liver-stage infections, we embarked on a messenger RNA (mRNA)-based vaccine strategy to induce liver Trm cells to prevent malaria.

Hydrogen bonding to oxygen in siloxane bonds drives liquid phase adsorption of primary alcohols in high-silica zeolites.

Upon liquid phase adsorption of C-C primary alcohols on high silica MFI zeolites (Si/Al = 11.5-140), the concentration of adsorbed molecules largely exceeds the concentration of traditional adsorption sites: Brønsted acid and defect sites. Combining quantitative H MAS NMR, qualitative multinuclear NMR and IR spectroscopy, hydrogen bonding of the alcohol function to oxygen atoms of the zeolite siloxane bridges (Si-O-Si) was shown to drive the additional adsorption.

Synthesis and Biological Evaluation of Peptide-Adjuvant Conjugate Vaccines with Increasing Antigen Content.

Synthetic vaccines that induce T cell responses to peptide epitopes are a promising immunotherapy for both communicable and noncommunicable diseases. Stimulating strong and sustained T cell responses requires antigen delivery to appropriately activated antigen presenting cells (APCs). One way this can be accomplished is by chemically conjugating immunogenic peptide epitopes with α-galactosylceramide (α-GalCer), a glycolipid that acts as an immune adjuvant by inducing stimulatory interactions between APCs and type I natural killer T (NKT) cells.

MAIT cells activate dendritic cells to promote T cell differentiation and induce humoral immunity.

Protective immune responses against respiratory pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus, are initiated by the mucosal immune system. However, most licensed vaccines are administered parenterally and are largely ineffective at inducing mucosal immunity. The development of safe and effective mucosal vaccines has been hampered by the lack of a suitable mucosal adjuvant.

Incorporation of SARS-CoV-2 spike NTD to RBD protein vaccine improves immunity against viral variants.

Emerging SARS-CoV-2 variants pose a threat to human health worldwide. SARS-CoV-2 receptor binding domain (RBD)-based vaccines are suitable candidates for booster vaccines, eliciting a focused antibody response enriched for virus neutralizing activity. Although RBD proteins are manufactured easily, and have excellent stability and safety properties, they are poorly immunogenic compared to the full-length spike protein.

An Atomistic Picture of Boron Oxide Catalysts for Oxidative Dehydrogenation Revealed by Ultrahigh Field B-O Solid-State NMR Spectroscopy.

Boron oxide/hydroxide supported on oxidized activated carbon (B/OAC) was shown to be an inexpensive catalyst for the oxidative dehydrogenation (ODH) of propane that offers activity and selectivity comparable to boron nitride. Here, we obtain an atomistic picture of the boron oxide/hydroxide layer in B/OAC by using 35.2 T B and O solid-state NMR experiments.

Using Full-Spectrum Flow Cytometry to Phenotype Memory T and NKT Cell Subsets with Optimized Tissue-Specific Preparation Protocols.

Full-spectrum flow cytometry is now routinely used in many laboratories internationally, and the demand for this technology is rapidly increasing. With capacity to use larger and more complex staining panels, standardized protocols are required for optimal panel design and analysis. Importantly, for ex vivo analysis, tissue preparation methods also need to be optimized to ensure samples are truly representative of tissues in situ.

Intratumoural administration of an NKT cell agonist with CpG promotes NKT cell infiltration associated with an enhanced antitumour response and abscopal effect.

Intratumoural administration of unmethylated cytosine-phosphate-guanine motifs (CpG) to stimulate toll-like receptor (TLR)-9 has been shown to induce tumour regression in preclinical studies and some efficacy in the clinic. Because activated natural killer T (NKT) cells can cooperate with pattern-recognition via TLRs to improve adaptive immune responses, we assessed the impact of combining a repeated dosing regimen of intratumoural CpG with a single intratumoural dose of the NKT cell agonist α-galactosylceramide (α-GalCer). The combination was superior to CpG alone at inducing regression of established tumours in several murine tumour models, primarily mediated by CD8 T cells.

6″-Modifed α-GalCer-peptide conjugate vaccine candidates protect against liver-stage malaria.

Self-adjuvanting vaccines consisting of peptide epitopes conjugated to immune adjuvants are a powerful way of generating antigen-specific immune responses. We previously showed that a -derived peptide conjugated to a rearranged form of α-galactosylceramide (α-GalCer) could stimulate liver-resident memory T (T) cells that were effective killers of liver-stage ANKA (Pba)-infected cells. To investigate if similar or even superior T responses can be induced by modifying the α-GalCer adjuvant, we created new conjugate vaccine cadidates by attaching an immunogenic -derived peptide antigen to 6″-substituted α-GalCer analogues.

Tumour infiltrating lymphocyte density differs by meningioma type and is associated with prognosis in atypical meningioma.

Tumour infiltrating lymphocyte (TIL) density is prognostically significant in various tumours, but few studies have investigated its significance in meningioma. This study aimed to investigate how TIL density differs by meningioma histology and whether it is a predictor of meningioma recurrence. We studied CD3, CD8, CD4, FOXP3 and PD-1 positive (+) TIL density in a continuous cohort of 476 meningiomas resected at Auckland Hospital between 2002 and 2011 using tissue microarrays and computer assisted image analysis.

Mucosal-Associated Invariant T (MAIT) Cell Dysfunction and PD-1 Expression in Prostate Cancer: Implications for Immunotherapy.

Prostate cancer is the second most common cancer in men worldwide. Despite an abundance of prostate-specific antigens, immunotherapies have yet to become a standard of care, potentially limited by T-cell dysfunction. Up to 10% of human circulating T-cells, and a significant fraction in the urogenital tract, are mucosal-associated invariant T (MAIT) cells.

Optical encoding of luminescent carbon nanodots in confined spaces.

Stable emissive carbon nanodots were generated in zeolite crystals using near infrared photon irradiation gradually converting the occluded organic template, originally used to synthesize the zeolite crystals, into discrete luminescent species consisting of nano-sized carbogenic fluorophores, as ascertained using Raman microscopy, and steady-state and time-resolved spectroscopic techniques. Photoactivation in a confocal laser fluorescence microscope allows 3D resolved writing of luminescent carbon nanodot patterns inside zeolites providing a cost-effective and non-toxic alternative to previously reported metal-based nanoclusters confined in zeolites, and opens up opportunities in bio-labelling and sensing applications.