Reliability of Goniometric Techniques for Measuring Hip Flexor Length Using the Modified Thomas Test.

Background: The modified Thomas test (MTT) is commonly used to assess the flexibility of hip musculature, including the iliopsoas, rectus femoris, and tensor fascia latae. This measurement is important to include in a comprehensive musculoskeletal examination. However, existing research shows conflicting results regarding its reliability, particularly due to variations in controlling pelvic tilt during testing, which may lead to inaccurate measurements of hip extension when quantifying the test outcomes.

Tropical estuarine ecosystem change under the interacting influences of future climate and ecosystem restoration.

One of the largest restoration programs in the world, the Comprehensive Everglades Restoration Plan (CERP) aims to restore freshwater inputs to Everglades wetlands and the Florida Bay estuary. This study predicted how the Florida Bay ecosystem may respond to hydrological restoration from CERP within the context of contemporary projected impacts of sea-level rise (SLR) and increased future temperatures. A spatial-temporal dynamic model (Ecospace) was used to develop a spatiotemporal food web model incorporating environmental drivers of salinity, salinity variation, temperature, depth, distance to mangrove, and seagrass abundance and was used to predict responses of biomass, fisheries catch, and ecosystem resilience between current and future conditions.

PRMT-1 and p120-Catenin as EMT Mediators in Osimertinib Resistance in NSCLC.

Osimertinib, an irreversible tyrosine kinase inhibitor, is a first-line therapy in EGFR-mutant NSCLC patients. Prolonged treatment with Osimertinib leads to resistance due to an acquired C797S mutation in the EGFR domain and other mechanisms, such as epithelial-mesenchymal transition (EMT). In this study, we investigated the role of PRMT-1 and p120-catenin in mediating Osimertinib resistance (OR) through EMT.

Benchmarking halcyon ring delivery system for hypofractionated breast radiotherapy: Validation and clinical implementation of the fast-forward trial.

Purpose: The aim of this study was to demonstrate the feasibility and efficacy of an iterative CBCT-guided breast radiotherapy with Fast-Forward trial of 26 Gy in five fractions on a Halcyon Linac. This study quantifies Halcyon plan quality, treatment delivery accuracy and efficacy by comparison with those of clinical TrueBeam plans.

Materials And Methods: Ten accelerated partial breast irradiation (APBI) patients (four right, six left) who underwent Fast-Forward trial at our institute on TrueBeam (6MV beam) were re-planned on Halcyon (6MV-FFF).

Learning Post-Stroke Gait Training Strategies by Modeling Patient-Therapist Interaction.

For safe and effective robot-aided gait training, it is essential to incorporate the knowledge and expertise of physical therapists. Toward this goal, we directly learn from physical therapists' demonstrations of manual gait assistance in stroke rehabilitation. Lower-limb kinematics of patients and assistive force applied by therapists to the patient's leg are measured using a wearable sensing system which includes a custom-made force sensing array.

Rapid Identification of MHCII-Binding Peptides Through Microsphere-Assisted Peptide Screening (MAPS).

CD4 T cells play a vital role in the immune response, and their function requires T cell receptor (TCR) recognition of peptide epitopes presented in complex with MHC class II (MHCII) molecules. Consequently, rapidly identifying peptides that bind MHCII is critical to understanding and treating infectious disease, cancer, autoimmunity, allergy, and transplant rejection. Computational methods provide a fast, ultrahigh-throughput approach to predict MHCII-binding peptides but lack the accuracy of experimental methods.

Rapid microsphere-assisted peptide screening (MAPS) of promiscuous MHCII-binding peptides in Zika virus envelope protein.

Despite promising developments in computational tools, peptide-class II MHC (MHCII) binding predictors continue to lag behind their peptide-class I MHC counterparts. Consequently, peptide-MHCII binding is often evaluated experimentally using competitive binding assays, which tend to sacrifice throughput for quantitative binding detail. Here, we developed a high-throughput semiquantitative peptide-MHCII screening strategy termed microsphere-assisted peptide screening (MAPS) that aims to balance the accuracy of competitive binding assays with the throughput of computational tools.

Context-Dependent Stabilizing Interactions among Solvent-Exposed Residues along the Surface of a Trimeric Helix Bundle.

Here we show that a solvent-exposed -position (i.e., residue 14) within a well-characterized trimeric helix bundle can facilitate a stabilizing long-range synergistic interaction involving -position Glu10 (i.

Incorporation of Aza-Glycine into Collagen Peptides.

Substitution of natural amino acids with their aza-amino acid counterparts in peptides has been a historically challenging prospect due to the diminished reactivity of the involved reagents. Current methods require lengthy reaction times or difficult synthetic strategies. Aza-glycine has proven to be a valuable tool in the design of triple-helix-forming collagen peptides.

Enhancing the Yield and Quality of Influenza Virus-like Particles (VLPs) Produced in Insect Cells by Inhibiting Cytopathic Effects of Matrix Protein M2.

To provide broader protection and eliminate the need for annual update of influenza vaccines, biomolecular engineering of influenza virus-like particles (VLPs) to display more conserved influenza proteins such as the matrix protein M2 has been explored. However, achieving high surface density of full-length M2 in influenza VLPs has been left unrealized. In this study, we show that the ion channel activity of M2 induces significant cytopathic effects in (Sf9) insect cells when expressed using M2-encoding baculovirus.

Construction and Screening of an Antigen-Derived Peptide Library Displayed on Yeast Cell Surface for CD4+ T Cell Epitope Identification.

Antigenic peptides (termed T cell epitopes) are assembled with major histocompatibility complex (MHC) molecules and presented on the surface of antigen-presenting cells (APCs) for T cell recognition. T cells engage these peptide-MHCs using T cell receptors (TCRs). Because T cell epitopes determine the specificity of a T cell immune response, their prediction and identification are important steps in developing peptide-based vaccines and immunotherapies.

Influence of PEGylation on the Strength of Protein Surface Salt Bridges.

Conjugation of polyethylene glycol (PEGylation) is a well-known strategy for extending the serum half-life of protein drugs and for increasing their resistance to proteolysis and aggregation. We previously showed that PEGylation can increase protein conformational stability; the extent of PEG-based stabilization depends on the PEGylation site, the structure of the PEG-protein linker, and the ability of PEG to release water molecules from the surrounding protein surface to the bulk solvent. The strength of a noncovalent interaction within a protein depends strongly on its microenvironment, with salt-bridge and hydrogen-bond strength increasing in nonpolar versus aqueous environments.

Elucidating structure-performance relationships in whole-cell cooperative enzyme catalysis.

Cooperative enzyme catalysis in nature has long inspired the application of engineered multi-enzyme assemblies for industrial biocatalysis. Despite considerable interest, efforts to harness the activity of cell-surface displayed multi-enzyme assemblies have been based on trial and error rather than rational design due to a lack of quantitative tools. In this study, we developed a quantitative approach to whole-cell biocatalyst characterization enabling a comprehensive study of how yeast-surface displayed multi-enzyme assemblies form.

Stapling of two PEGylated side chains increases the conformational stability of the WW domain via an entropic effect.

Hydrocarbon stapling and PEGylation are distinct strategies for enhancing the conformational stability and/or pharmacokinetic properties of peptide and protein drugs. Here we combine these approaches by incorporating asparagine-linked O-allyl PEG oligomers at two positions within the β-sheet protein WW, followed by stapling of the PEGs via olefin metathesis. The impact of stapling two sites that are close in primary sequence is small relative to the impact of PEGylation alone and depends strongly on PEG length.

Protein-Scaffold Directed Nanoscale Assembly of T Cell Ligands: Artificial Antigen Presentation with Defined Valency, Density, and Ratio.

Tuning antigen presentation to T cells is a critical step in investigating key aspects of T cell activation. However, existing technologies have a limited ability to control the spatial and stoichiometric organization of T cell ligands on 3D surfaces. Here, we developed an artificial antigen presentation platform based on protein scaffold-directed assembly that allows fine control over the spatial and stoichiometric organization of T cell ligands on a 3D yeast cell surface.

Bulky Dehydroamino Acids Enhance Proteolytic Stability and Folding in β-Hairpin Peptides.

The bulky dehydroamino acids dehydrovaline (ΔVal) and dehydroethylnorvaline (ΔEnv) can be inserted into the turn regions of β-hairpin peptides without altering their secondary structures. These residues increase proteolytic stability, with ΔVal at the (i + 1) position having the most substantial impact. Additionally, a bulky dehydroamino acid can be paired with a d-amino acid (i.

An Anion-π Interaction Strongly Stabilizes the β-Sheet Protein WW.

Anions have long been known to engage in stabilizing interactions with electron-deficient arenes. However, the precise nature and energetic contribution of anion-π interactions to protein stability remains a subject of debate. Here, we show that placing a negatively charged Asp in close proximity to electron-rich Phe in a reverse turn within the WW domain results in a favorable interaction that increases WW conformational stability by -1.

Enhancing a long-range salt bridge with intermediate aromatic and nonpolar amino acids.

The interaction of a positively charged amino acid residue with a negatively charged residue (i.e. a salt bridge) can contribute substantially to protein conformational stability, especially when two ionic groups are in close proximity.

Revealing pMDI Spray Initial Conditions: Flashing, Atomisation and the Effect of Ethanol.

Purpose: Sprays from pressurised metered-dose inhalers are produced by a transient discharge of a multiphase mixture. Small length and short time scales have made the investigation of the governing processes difficult. Consequently, a deep understanding of the physical processes that govern atomisation and drug particle formation has been elusive.

Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography.

Purpose: Typical methods to study pMDI sprays employ particle sizing or visible light diagnostics, which suffer in regions of high spray density. X-ray techniques can be applied to pharmaceutical sprays to obtain information unattainable by conventional particle sizing and light-based techniques.

Methods: We present a technique for obtaining quantitative measurements of spray density in pMDI sprays.

Temporally and Spatially Resolved x-ray Fluorescence Measurements of in-situ Drug Concentration in Metered-Dose Inhaler Sprays.

Purpose: Drug concentration measurements in MDI sprays are typically performed using particle filtration or laser scattering. These techniques are ineffective in proximity to the nozzle, making it difficult to determine how factors such as nozzle design will affect the precipitation of co-solvent droplets in solution-based MDIs, and the final particle distribution.

Methods: In optical measurements, scattering from the constituents is difficult to separate.

Engineering Novel and Improved Biocatalysts by Cell Surface Display.

Biocatalysts, especially enzymes, have the ability to catalyze reactions with high product selectivity, utilize a broad range of substrates, and maintain activity at low temperature and pressure. Therefore, they represent a renewable, environmentally friendly alternative to conventional catalysts. Most current industrial-scale chemical production processes using biocatalysts employ soluble enzymes or whole cells expressing intracellular enzymes.

Criteria for selecting PEGylation sites on proteins for higher thermodynamic and proteolytic stability.

PEGylation of protein side chains has been used for more than 30 years to enhance the pharmacokinetic properties of protein drugs. However, there are no structure- or sequence-based guidelines for selecting sites that provide optimal PEG-based pharmacokinetic enhancement with minimal losses to biological activity. We hypothesize that globally optimal PEGylation sites are characterized by the ability of the PEG oligomer to increase protein conformational stability; however, the current understanding of how PEG influences the conformational stability of proteins is incomplete.

Cys(i)-Lys(i+3)-Lys(i+4) triad: a general approach for PEG-based stabilization of α-helical proteins.

PEGylation is an important strategy for enhancing the pharmacokinetic properties of protein drugs. Modern chemoselective reactions now enable specific placement of a single PEG at any site on a protein surface. However, few rational structure-based guidelines exist for selecting optimal PEGylation sites.