Toolkit to Examine Lifelike Language v.2.0: Optimizing Speech Biomarkers of Neurodegeneration.

Introduction: The Toolkit to Examine Lifelike Language (TELL) is a web-based application providing speech biomarkers of neurodegeneration. After deployment of TELL v.1.

Evaluating the Potential of Cyclodextrins in Reducing Aggregation of Antibody-Drug Conjugates with Different Payloads.

Cyclodextrins (CDs) are versatile agents used to solubilize small drugs and stabilize proteins. This dual functionality may be particularly beneficial for antibody-drug conjugates (ADCs), as CDs may "mask" the hydrophobicity of the drug payloads. In this study, we explored the effect of CDs on the physical stability of ADCs composed of the same antibody but with different payloads (maytansinoid, auristatin, and fluorophore payloads).

"Negative" Impact: The Role of Payload Charge in the Physicochemical Stability of Auristatin Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) tend to be less stable than their parent antibodies, which is often attributed to the hydrophobic nature of their drug payloads. This study investigated how the payload charge affects ADC stability by comparing two interchain cysteine ADCs that had matched drug-to-antibody ratios and identical linkers but differently charged auristatin payloads, vcMMAE (neutral) and vcMMAF (negative). Both ADCs exhibited higher aggregation than their parent antibody under shaking stress and thermal stress conditions.

Features in Backgrounds of Microscopy Images Introduce Biases in Machine Learning Analyses.

Subvisible particles may be encountered throughout the processing of therapeutic protein formulations. Flow imaging microscopy (FIM) and backgrounded membrane imaging (BMI) are techniques commonly used to record digital images of these particles, which may be analyzed to provide particle size distributions, concentrations, and identities. Although both techniques record digital images of particles within a sample, FIM analyzes particles suspended in flowing liquids, whereas BMI records images of dry particles after collection by filtration onto a membrane.

Agitation-Induced Aggregation of Lysine- And Interchain Cysteine-Linked Antibody-Drug Conjugates.

Drug conjugation to an antibody can affect its stability, which depends on factors such as the conjugation technique used, drug-linker properties, and stress encountered. This study focused on the effects of agitation stress on the physical stability of two lysine (ADC-K) and two interchain cysteine (ADC-C) conjugates of an IgG monoclonal antibody (mAb) linked to either ∼4 MMAE or DM1 payloads. During agitation, all antibody-drug conjugates (ADCs) exhibited higher aggregation than the mAb, which was dependent on the conjugation technique (aggregation of ADC-Ks > ADC-Cs) and drug-linker (aggregation of ADCs with MMAE > ADCs with DM1).

Toolkit to Examine Lifelike Language (TELL): An app to capture speech and language markers of neurodegeneration.

Automated speech and language analysis (ASLA) is a promising approach for capturing early markers of neurodegenerative diseases. However, its potential remains underexploited in research and translational settings, partly due to the lack of a unified tool for data collection, encryption, processing, download, and visualization. Here we introduce the Toolkit to Examine Lifelike Language (TELL) v.

Miniaturized Forced Degradation of Therapeutic Proteins and ADCs by Agitation-Induced Aggregation Using Orbital Shaking of Microplates.

Microplate-based formulation screening is a powerful approach to identify stabilizing excipients for therapeutic proteins while reducing material requirements. However, this approach is sometimes not representative of studies conducted in relevant container closures. The present study aimed to identify critical parameters for a microplate-based orbital shaking method to screen biotherapeutic formulations by agitation-induced aggregation.

What waste management can learn from the traditional mining sector: Towards an integrated assessment and reporting of anthropogenic resources.

Many organizations in Europe collect data and perform research on municipal solid waste and the secondary raw materials that can be produced from them through recycling, urban mining, or landfill mining. However, the information generated and presented thereby is often highly aggregated, while research activities are many a time isolated. Both reduce the usability of the data and information generated.

Index of suspicion with appropriate timing of CT scan helps prevent missed diagnosis in urologic trauma.

Ureteric and bladder injuries are uncommon, difficult to diagnose and rarely occur in isolation. Diagnosis is often delayed or missed at presentation. Therefore, high clinical suspicion and appropriate timing of computed tomography (CT) are of paramount importance.

Deterministic Switching in Bismuth Ferrite Nanoislands.

We report deterministic selection of polarization variant in bismuth BiFeO3 nanoislands via a two-step scanning probe microscopy procedure. The polarization orientation in a nanoisland is toggled to the desired variant after a reset operation by scanning a conductive atomic force probe in contact over the surface while a bias is applied. The final polarization variant is determined by the direction of the inhomogeneous in-plane trailing field associated with the moving probe tip.

Structure-charge relationship - the case of hematite (001).

We present a multidisciplinary study on the hematite (001)-aqueous solution interface, in particular the relationship between surface structure (studied via surface diffraction in a humid atmosphere) and the macroscopic charging (studied via surface- and zeta-potential measurements in electrolyte solutions as a function of pH). Upon aging in water changes in the surface structure are observed, that are accompanied by drastic changes in the zeta-potential. Surprisingly the surface potential is not accordingly affected.

Ferroelectric nanostructures fabricated by focused-ion-beam milling in epitaxial BiFeO3 thin films.

We studied a suitable route to fabricate ferroelectric islands by focused-ion-beam milling in bismuth ferrite epitaxial thin films. Piezoresponse force microscopy shows that the damage induced by the milling process is extended to 1 µm away from the edge of the focused-ion-beam patterned islands. After a combined vacuum and oxygen atmosphere annealing procedure, ferroelectricity is fully recovered in structures with sizes down to 500 nm, while for 250 nm islands the defects at the interfaces induce polarization direction pinning.

Ultra-smooth lithium niobate photonic micro-structures by surface tension reshaping.

Annealing of micro-structured lithium niobate substrates at temperatures close to, but below the melting point, allows surface tension to reshape preferentially melted surface zones of the crystal. The reshaped surface re-crystallizes upon cooling to form a single crystal again as it is seeded by the bulk which remains solid throughout the process. This procedure yields ultra-smooth single crystal superstructures suitable for the fabrication of photonic micro-components with low scattering loss.

Spectral and electro-optic response of UV-written waveguides in LiNbO3 single crystals.

An experimental study of the spectral and electro-optic response of direct UV-written waveguides in LiNbO3 is reported. The waveguides were written using c.w.

Development of a tandem-electrostatic-quadrupole accelerator facility for BNCT.

In this work we describe the present status of an ongoing project to develop a tandem-electrostatic-quadrupole (TESQ) accelerator facility for accelerator-based (AB) BNCT at the Atomic Energy Commission of Argentina in Buenos Aires. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the (7)Li(p,n)(7)Be reaction slightly beyond its resonance at 2.