Experimental demonstration of in situ surface and thickness profile measurements of thin film during deposition using a grating array based wavefront sensor.

Here we introduce an in situ and non-intrusive surface and thickness profile monitoring scheme of thin-film growth during deposition. The scheme is implemented using a programmable grating array based zonal wavefront sensor integrated with a thin-film deposition unit. It provides both 2D surface and thickness profiles of any reflecting thin film during deposition without requiring the properties of the thin-film material.

Material platform for realization of a "fiber-like" lossy mode resonance response in a simple Kretschmann-Raether geometry: publisher's note.

This publisher's note contains corrections to Opt. Lett.46, 3065 (2021).

Material platform for realization of a "fiber-like" lossy mode resonance response in a simple Kretschmann-Raether geometry.

The lossy mode resonance (LMR) phenomenon is almost exclusively limited to fiber optics, since the thin film configuration yields a relatively shallow resonance dip compared to its fiber counterpart. In this Letter, we bridge this frustrating intensity gap between these basic configurations by choosing vacuum-deposited metallic indium-rich indium tin oxide as the coating material. LMR attenuation as high as -14.

Challenges of Using Closed System Transfer Devices With Biological Drug Products: An Industry Perspective.

Hazardous drug is a common term used by the National Institute of Occupational Health and Safety (NIOSH) to classify medications that may induce adverse mutagenic and reproductive responses in health care personnel. NIOSH publishes a list of drugs it defines as hazardous where it may be appropriate for health care workers to take protective measures to reduce the potential for occupational exposure. Recent updates and proposed updates to this list have included large molecule biological products with oncology indications.

Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development.

Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions.

Distinct encounter complexes of PAI-1 with plasminogen activators and vitronectin revealed by changes in the conformation and dynamics of the reactive center loop.

Unlabelled: Plasminogen activator inhibitor-1 (PAI-1) is a biologically important serine protease inhibitor (serpin) that, when overexpressed, is associated with a high risk for cardiovascular disease and cancer metastasis. Several of its ligands, including vitronectin, tissue-type and urokinase-type plasminogen activator (tPA, uPA), affect the fate of PAI-1. Here, we measured changes in the solvent accessibility and dynamics of an important unresolved functional region, the reactive center loop (RCL), upon binding of these ligands.

Rational design of viscosity reducing mutants of a monoclonal antibody: hydrophobic versus electrostatic inter-molecular interactions.

High viscosity of monoclonal antibody formulations at concentrations ≥100 mg/mL can impede their development as products suitable for subcutaneous delivery. The effects of hydrophobic and electrostatic intermolecular interactions on the solution behavior of MAB 1, which becomes unacceptably viscous at high concentrations, was studied by testing 5 single point mutants. The mutations were designed to reduce viscosity by disrupting either an aggregation prone region (APR), which also participates in 2 hydrophobic surface patches, or a negatively charged surface patch in the variable region.

Activation of the zymogen to urokinase-type plasminogen activator is associated with increased interdomain flexibility.

A key regulatory step for serine proteases of the trypsin clan is activation of the initially secreted zymogens, leading to an increase in activity by orders of magnitude. Zymogen activation occurs by cleavage of a single peptide bond near the N-terminus of the catalytic domain. Besides the catalytic domain, most serine proteases have N-terminal A-chains with independently folded domains.

Metals affect the structure and activity of human plasminogen activator inhibitor-1. II. Binding affinity and conformational changes.

Human plasminogen activator inhibitor type 1 (PAI-1) is a serine protease inhibitor with a metastable active conformation. The lifespan of the active form of PAI-1 is modulated via interaction with the plasma protein, vitronectin, and various metal ions. These metal ions fall into two categories: Type I metals, including calcium, magnesium, and manganese, stabilize PAI-1 in the absence of vitronectin, whereas Type II metals, including cobalt, copper, and nickel, destabilize PAI-1 in the absence of vitronectin, but stabilize PAI-1 in its presence.

Metals affect the structure and activity of human plasminogen activator inhibitor-1. I. Modulation of stability and protease inhibition.

Human plasminogen activator inhibitor type 1 (PAI-1) is a serine protease inhibitor with a metastable active conformation. Under physiological conditions, half of the inhibitor transitions to a latent state within 1-2 h. The interaction between PAI-1 and the plasma protein vitronectin prolongs this active lifespan by ∼50%.

Radical redesign of a tandem array of four R67 dihydrofolate reductase genes yields a functional, folded protein possessing 45 substitutions.

R67 dihydrofolate reductase (DHFR) is a plasmid-encoded, type II enzyme. Four monomers (78 amino acids long) assemble into a homotetramer possessing 222 symmetry. In previous studies, a tandem array of four R67 DHFR gene copies was fused in frame to generate a functional monomer named Quad1.

R67, the other dihydrofolate reductase: rational design of an alternate active site configuration.

R67 dihydrofolate reductase (DHFR) bears no sequence or structural homologies with chromosomal DHFRs. The gene for this enzyme produces subunits that are 78 amino acids long, which assemble into a homotetramer possessing 222 symmetry. More recently, a tandem array of four gene copies linked in-frame was constructed, which produces a monomer containing 312 amino acids named Quad3.

Alprazolam induced conformational change in hemoglobin.

Alprazolam (ALP) is a widely prescribed sedative and antidepressant benzodiazepine group of drugs. The wide uses of this drug lead us to investigate its possible interaction with hemoglobin (Hb). Spectrophotometric and spectofluorimetric studies showed strong binding of ALP with Hb.