Fe-Doped Ni-Based Catalysts Surpass Ir-Baselines for Oxygen Evolution Due to Optimal Charge-Transfer Characteristics.

Ni-based catalysts with Co or Fe can potentially replace precious Ir-based catalysts for the rate-limiting oxygen evolution reaction (OER) in anion-exchange membrane (AEM) electrolyzers. In this study, density functional theory (DFT) calculations provide atomic- and electronic-level resolution on how the inclusion of Co or Fe can overcome the inactivity of NiO catalysts and even enable them to surpass IrO in activating key steps to the OER. Namely, NiO resists binding the key OH* intermediate and presents a high energetic barrier to forming the O*.

Decreased solubility and increased adsorptivity of a biotinylated humanized anti-cocaine mAb.

Biotinylation of proteins, including antibodies, is a very useful and important modification for a variety of biochemical characterizations, including anti-drug antibody (ADA) assays used to detect antibodies raised against therapeutic antibodies. We assessed different degrees of biotin labeling of an anti-cocaine mAb currently under development for treating cocaine use disorder. We noted that higher levels of biotin labeling dramatically decreased mAb solubility, and increased the tendency to bind to surfaces, complicating characterization of the biotinylated antibody.

Pulsed Laser Deposition of Epitaxial SrTiO/SrAlO Templates as a Water-Soluble Sacrificial Layer for GaAs Growth and Lift-Off.

Despite the record-high efficiency of GaAs solar cells, their terrestrial application is limited due to both the particularly high costs related to the required single-crystal substrates and epitaxial growth. A water-soluble lift-off layer could reduce costs by avoiding the need for toxic and dangerous etchants, substrate repolishing, and expensive process steps. SrAlO (SAO) is a water-soluble cubic oxide, and SrTiO (STO) is a perovskite oxide, where ≈ 4 × ≈ (2√2) .

Mn Additive Improves Zr Grain Boundary Diffusion for Sintering of a Y-Doped BaZrO Proton Conductor.

Yttrium-doped barium zirconate (BZY) has garnered attention as a protonic conductor in intermediate-temperature electrolysis and fuel cells due to its high bulk proton conductivity and excellent chemical stability. However, the performance of BZY can be further enhanced by reducing the concentration and resistance of grain boundaries. In this study, we investigate the impact of manganese (Mn) additives on the sinterability and proton conductivity of Y-doped BaZrO (BZY).

Novel partial reduction of the humanized anti-cocaine mAb h2E2 for selective cysteine labeling.

Monoclonal antibodies are utilized for treating many diseases and disorders, as well as for basic research and development. Covalent labeling of mAbs is important for various antibody applications and creating antibody drug conjugates. Labeling at reactive lysine residues using lysine selective reagents is useful, but is non-selective and can interfere with antigen binding and interactions of the Fc antibody region.

Differential Effect of Fixed Ratio Magnitude on the Rate of Lever-Pressing and Interinjection Intervals of Cocaine Self-Administration in Rats.

Background: Many features of self-administration behavior may be explained by reference to the properties of schedules of reinforcement. Schedules alter the probability of a behavior being reinforced and thereby increase, or decrease, the frequency of the behavior and fixed ratio (FR) magnitude reportedly alters the rate of responding to cocaine. A pharmacokinetic/pharmacodynamic interaction theory states that lever-pressing behavior is induced only when cocaine levels in the body are above the priming/remission threshold and below the satiety threshold-a range termed the compulsion zone.

Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivity.

A humanized monoclonal antibody h2E2 designed to bind cocaine with high affinity, specificity, and a long half-life (~7 d in rats) is being developed as a treatment for cocaine use disorder. We report here a pharmacokinetic (PK) study of h2E2 using male and female rats conducted under a Good Laboratory Practice (GLP) protocol over a dose range of 40 to 1200 mg/kg. The maximum concentration measured in rat plasma (C) varied proportionately to the dose administered in both male and female rats.

The ascending limb of the cocaine unit dose-response function in rats as an experimental artifact.

The cocaine unit dose-response function is an inverted U with the ascending and descending limbs representing the positive and rate limiting cocaine effects, respectively. Higher fixed ratio (FR) schedules and/or time-out periods make the ascending limb more prominent. Alternatively, a pharmacokinetic/pharmacodynamic interaction theory demonstrates that cocaine-induced lever pressing occurs only when cocaine levels are within a range termed the compulsion zone.

SCH23390 and a humanized anti-cocaine mAb decrease the latency to cocaine-induced reinstatement of lever pressing behavior in rats that self-administer cocaine.

In rats that self-administer cocaine, the latency to the reinstatement of lever pressing behavior induced by a single dose of cocaine is due to the time taken for cocaine levels to fall to the satiety threshold. The D1 dopamine receptor antagonist SCH23390, and the recombinant humanized anti-cocaine mAb h2E2 increase the cocaine satiety threshold and would be expected to alter the latency to reinstatement. Male rats acquired cocaine self-administration behavior on an FR1 schedule.

Characterization and optimization of fluorescein isothiocyanate labeling of humanized h2E2 anti-cocaine mAb.

Fluorescein isothiocyanate (FITC) is widely used to fluorescently label reactive lysine residues on proteins, including antibodies. The rate and extent of labeling varies with reaction conditions, concentration of label, and the concentration and nature of the protein. Fluorescently labeled proteins are very useful, and one use for FITC labeled mAbs is development of assays to measure anti-mAb antibodies produced during treatment with antibody therapeutics.

The cocaine compulsion zone theory explains the reinstatement of lever pressing behavior in rats in response to a single cocaine dose.

A single non-contingent dose of cocaine reinstates extinguished lever pressing behavior in rats trained to self-administer cocaine. This represents a model of relapse in cocaine use disorder and the number of lever presses has been the standard measure. Lever pressing behavior during self-administration occurs only when cocaine levels are below the satiety threshold and above the remission/priming threshold, a range termed the compulsion zone.

Reformulation and Thermal Stability of a Therapeutic Anti-Cocaine mAb.

We concentrated and reformulated the anti-cocaine mAb, h2E2, to reduce the amount of sucrose and histidine buffer infused with the mAb, to satisfy FDA maximum exposure levels for those components for use in clinical trials. After concentration of the original 20 mg/ml mAb, 4 reformulation buffers were evaluated for suitability. The concentration of histidine was reduced from 10 mM to 3 or 0 mM, and the concentration of sucrose reduced from 10% to 2, 4, or 6%.

A humanized anti-cocaine mAb antagonizes the cardiovascular effects of cocaine in rats.

The recombinant monoclonal anti-cocaine antibody, h2E2, sequesters cocaine in plasma increasing concentrations more than 10-fold. The increased levels of cocaine in the plasma could have detrimental peripheral effects, particularly on the cardiovascular system. We investigated the duration and magnitude of the effect of cocaine on the rat heart, and if h2E2 could antagonize that effect.

The progressive ratio and fixed ratio 1 schedules of cocaine self-administration in rats convey the same information.

Progressive ratio (PR) schedules of drug delivery are used to determine the 'motivational' state of an animal and drug 'reinforcing efficacy'. This widely held interpretation is supported mainly by the observation that the PR breakpoint (BP) is proportional to the unit dose of self-administered drug. The compulsion zone theory of cocaine self-administration was applied to determine whether it can explain the pattern of lever-pressing behavior and cocaine injections under the PR schedule in rats.

Clinical utility of reticulocyte haemoglobin in the assessment of iron deficiency and iron deficiency anaemia in the paediatric population.

Aim: Reticulocyte haemoglobin (Ret-He) is a useful marker in the assessment of iron stores in adult and paediatric patients. It is currently not utilised in Pathology Queensland. The objective of this study is to verify Ret-He in our Pathology Queensland laboratory and assess the clinical utility in the assessment of iron deficiency (ID) and iron deficiency anaemia (IDA) in paediatric patients.

Isothermal titration calorimetry determination of thermodynamics of binding of cocaine and its metabolites to humanized h2E2 anti-cocaine mAb.

We analyzed the thermodynamics of binding of cocaine and several cocaine metabolites to a humanized anti-cocaine mAb (h2E2), which is under development for the treatment of cocaine use disorders, using isothermal titration calorimetry. The calculated equilibrium dissociation (binding) constants were consistent with previous findings using other methods. All three ligands that display high affinity (nM) binding to the mAb (cocaine, cocaethylene, and benzoylecgonine) displayed similar enthalpically driven binding with substantial enthalpy-entropy compensation.

Effects of a recombinant humanized anti-cocaine monoclonal antibody on the metabolism and distribution of cocaine in vitro and in mice.

The anti-cocaine monoclonal antibody, h2E2, is a candidate for treating cocaine-use disorder. h2E2 binds to and sequesters cocaine in the plasma compartment, effectively decreasing cocaine concentrations in the brains of rats and mice. Despite the binding of cocaine to h2E2, plasma cocaine concentrations decline rapidly in rodents over time, but there was a drastic decrease in the urinary elimination of cocaine in the presence of h2E2.

Critical evaluation of fluorescent dyes to evaluate the stability and ligand binding properties of an anti-cocaine mAb, h2E2.

Monoclonal antibodies have become a mainstay of modern drug development. However, unlike small molecule drugs, mAbs are large proteins that need to be characterized for their stability, heterogeneity, and tendency to aggregate. Many different extrinsic fluorescent dyes have been used to monitor the thermal stability, aggregation, and ligand binding characteristics of many different proteins.

Differential effects of acute and chronic antagonist and an irreversible antagonist treatment on cocaine self-administration behavior in rats.

According to pharmacological theory, the magnitude of an agonist-induced response is related to the number of receptors occupied. If there is a receptor reserve, when the number of receptors is altered the fractional occupancy required to maintain this set number of receptors will change. Therefore, any change in dopamine receptor number will result in a change in the concentration of cocaine required to induce the satiety response.

Tyrosine nitration of a humanized anti-cocaine mAb differentially affects ligand binding of cocaine and its metabolites.

Tetranitromethane was used to selectively modify tyrosine residues of a humanized anti-cocaine mAb (h2E2), under development for the treatment of cocaine use disorders. The effect of mild tyrosine nitration on the affinity of cocaine and two high affinity cocaine metabolites, cocaethylene and benzoylecgonine, was assessed using differential scanning fluorimetry to measure ligand affinities via ligand-induced thermal stabilization of the mAb antigen binding region. Nitrated tyrosine residues were identified by mass spectral analysis of thermolysin peptides.

Oxidation of specific tryptophan residues inhibits high-affinity binding of cocaine and its metabolites to a humanized anticocaine mAb.

Cocaine addiction remains a serious problem lacking an effective pharmacological treatment. Thus, we have developed a high-affinity anti-cocaine monoclonal antibody (mAb), h2E2, for the treatment of cocaine use disorders. We show that selective tryptophan (Trp) oxidation by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) resulted in a loss of high-affinity binding of cocaine to this mAb.

The compulsion zone explains the self-administration of cocaine, RTI-55 and bupropion in rats.

Rats that reliably self-administered cocaine also reliably self-administered the cocaine analog RTI-55 and bupropion. The inter-injection intervals of these dopamine transporter (DAT) inhibitors were regular at a given unit dose and increased as a function of unit dose. However, the mean rate of intake differed widely, ranging from 731 to 459 to 2.

Accelerating Hydrogen Absorption and Desorption Rates in Palladium Nanocubes with an Ultrathin Surface Modification.

Exploiting the high surface-area-to-volume ratio of nanomaterials to store energy in the form of electrochemical alloys is an exceptionally promising route for achieving high-rate energy storage and delivery. Nanoscale palladium hydride is an excellent model system for understanding how nanoscale-specific properties affect the absorption and desorption of energy carrying equivalents. Hydrogen absorption and desorption in shape-controlled Pd nanostructures does not occur uniformly across the entire nanoparticle surface.

Dramatic increase in lever-pressing activity in rats after training on the progressive ratio schedule of cocaine self-administration.

Transition from the highest rate of lever-pressing activity during the unloading (extinction) phase of a cocaine self-administration session to an extremely low activity rate during the remission phase is in many cases gradual. This makes it difficult to assess the duration of the unloading phase after a fixed ratio 1 (FR1) or breakpoint after a progressive-ratio (PR) self-administration session. In addition, 3-5 days of training under the PR schedule results in a dramatic and persistent increase in the rate of presses during PR sessions and in the unloading phase following FR1 self-administration sessions.

Cocaine binding to the Fab fragment of a humanized anti-cocaine mAb quantitated by dye absorption and fluorescence spectroscopy.

In this work, we establish that cocaine binding to the Fab fragment of a recombinant humanized anti-cocaine mAb (h2E2) can be directly and easily quantitated using simple and inexpensive absorption and fluorescence measurements, employing dyes typically used for differential scanning fluorimetry, DASPMI and SYPRO Orange. For concentrated samples of the Fab fragment, absorbance spectroscopy employing these dyes reveals the number of cocaine sites present, using either DASPMI (by measuring the increase in dye absorbance) or SYPRO Orange (by measuring the change in dye maximal absorbance wavelength). Interestingly, we observed that cocaine binding to the Fab fragment had a much different effect on the SYPRO Orange dye absorbance than previously reported for the intact h2E2 mAb, resulting in a large decrease in the total dye absorbance for the Fab fragment, in contrast to previous results with the intact h2E2 mAb.