Sub-Visible Particle Classification and Label Consistency Analysis for Flow-Imaging Microscopy Via Machine Learning Methods.

Sub-visible particles can be a quality concern in pharmaceutical products, especially parenteral preparations. To quantify and characterize these particles, liquid samples may be passed through a flow-imaging microscopy instrument that also generates images of each detected particle. Machine learning techniques have increasingly been applied to this kind of data to detect changes in experimental conditions or classify specific types of particles, primarily focusing on silicone oil.

Size-dependent deformation behavior in nanosized amorphous metals suggesting transition from collective to individual atomic transport.

The underlying atomistic mechanism of deformation is a central problem in mechanics and materials science. Whereas deformation of crystalline metals is fundamentally understood, the understanding of deformation of amorphous metals lacks behind, particularly identifying the involved temporal and spatial scales. Here, we reveal that at small scales the size-dependent deformation behavior of amorphous metals significantly deviates from homogeneous flow, exhibiting increasing deformation rate with reducing size and gradually shifted composition.

Compositional dependence of the fragility in metallic glass forming liquids.

The viscosity and its temperature dependence, the fragility, are key properties of a liquid. A low fragility is believed to promote the formation of metallic glasses. Yet, the fragility remains poorly understood, since experimental data of its compositional dependence are scarce.

Combinatorial measurement of critical cooling rates in aluminum-base metallic glass forming alloys.

Direct measurement of critical cooling rates has been challenging and only determined for a minute fraction of the reported metallic glass forming alloys. Here, we report a method that directly measures critical cooling rate of thin film metallic glass forming alloys in a combinatorial fashion. Based on a universal heating architecture using indirect laser heating and a microstructure analysis this method offers itself as a rapid screening technique to quantify glass forming ability.

Janus electrocatalytic flow-through membrane enables highly selective singlet oxygen production.

The importance of singlet oxygen (O) in the environmental and biomedical fields has motivated research for effective O production. Electrocatalytic processes hold great potential for highly-automated and scalable O synthesis, but they are energy- and chemical-intensive. Herein, we present a Janus electrocatalytic membrane realizing ultra-efficient O production (6.

Atomic-Scale Imprinting by Sputter Deposition of Amorphous Metallic Films.

With its ease of implementation, low cost, high throughput, and excellent feature replication accuracy, nanoimprinting is used to fabricate structures for electrical, optical, and biological applications or to modify surface properties. If ultraprecise and/or subnanometer-sized patterns are desired, nanoimprinting has shown only limited success with polymers, silica glasses, or crystalline materials. In contrast, the absence of an intrinsic length scale that would interfere with imprinting resolution enables bulk metallic glasses (BMGs) to replicate structures down to the atomic scale through thermoplastic forming (TPF).

Rational optimization of a monoclonal antibody improves the aggregation propensity and enhances the CMC properties along the entire pharmaceutical process chain.

The discovery of therapeutic monoclonal antibodies (mAbs) primarily focuses on their biological activity favoring the selection of highly potent drug candidates. These candidates, however, may have physical or chemical attributes that lead to unfavorable chemistry, manufacturing, and control (CMC) properties, such as low product titers, conformational and colloidal instabilities, or poor solubility, which can hamper or even prevent development and manufacturing. Hence, there is an urgent need to consider the developability of mAb candidates during lead identification and optimization.

Semiconductor-to-conductor transition in 2D copper(ii) oxide nanosheets through surface sulfur-functionalization.

Functionalization is a widely-used strategy to modulate and optimize the properties of materials towards various applications, including sensing, catalysis, and energy generation. While the influence of sulfur-functionalization of carbon materials and oxides like ZnO and TiO has been studied, far less research has been devoted to analyzing sulfur-functionalization of CuO and other transition metal oxide nanomaterials. Here, we report sulfur-functionalization of copper(ii) oxide nanosheets synthesized by using a soft-templating procedure, with sulfur-addition based on hydrogen sulfide gas as a source.

Adaption of human antibody λ and κ light chain architectures to CDR repertoires.

Monoclonal antibodies bind with high specificity to a wide range of diverse antigens, primarily mediated by their hypervariable complementarity determining regions (CDRs). The defined antigen binding loops are supported by the structurally conserved β-sandwich framework of the light chain (LC) and heavy chain (HC) variable regions. The LC genes are encoded by two separate loci, subdividing the entity of antibodies into kappa (LCκ) and lambda (LCλ) isotypes that exhibit distinct sequence and conformational preferences.

Formation and stability of complex metallic phases including quasicrystals explored through combinatorial methods.

Aluminum-based quasicrystals typically form across narrow composition ranges within binary to quaternary alloys, which makes their fabrication and characterization challenging. Here, we use combinatorial approaches together with fast characterization techniques to study a wide compositional range including known quasicrystal forming compositions. Specifically, we use magnetron co-sputtering to fabricate libraries of ~140 Al-Cu-Fe and ~300 Al-Cu-Fe-Cr alloys.

Structure of a Therapeutic Full-Length Anti-NPRA IgG4 Antibody: Dissecting Conformational Diversity.

We report the x-ray crystal structure of intact, full-length human immunoglobulin (IgG4) at 1.8 Å resolution. The data for IgG4 (S228P), an antibody targeting the natriuretic peptide receptor A, show a previously unrecognized type of Fab-Fc orientation with a distorted λ-shape in which one Fab-arm is oriented toward the Fc portion.

Author Correction: Determination of critical cooling rates in metallic glass forming alloy libraries through laser spike annealing.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Improved Solution-State Properties of Monoclonal Antibodies by Targeted Mutations.

Monoclonal antibody (mAb)-based therapeutics often require high-concentration formulations. Unfortunately, highly concentrated antibody solutions often have biophysical properties that are disadvantageous for therapeutic development, such as high viscosity, solubility limitations, precipitation issues, or liquid-liquid phase separation. In this work, we present a computational rational design principle for improving the thermodynamic stability of mAb solutions through targeted point mutations.

Determination of critical cooling rates in metallic glass forming alloy libraries through laser spike annealing.

The glass forming ability (GFA) of metallic glasses (MGs) is quantified by the critical cooling rate (R ). Despite its key role in MG research, experimental challenges have limited measured R to a minute fraction of known glass formers. We present a combinatorial approach to directly measure R for large compositional ranges.

Proteasome assembly from 15S precursors involves major conformational changes and recycling of the Pba1-Pba2 chaperone.

The chaperones Ump1 and Pba1-Pba2 promote efficient biogenesis of 20S proteasome core particles from its subunits via 15S intermediates containing alpha and beta subunits, except beta7. Here we elucidate the structural role of these chaperones in late steps of core particle biogenesis using biochemical, electron microscopy, cross-linking and mass spectrometry analyses. In 15S precursor complexes, Ump1 is largely unstructured, lining the inner cavity of the complex along the interface between alpha and beta subunits.

Structure of the VipA/B type VI secretion complex suggests a contraction-state-specific recycling mechanism.

The bacterial type VI secretion system is a multicomponent molecular machine directed against eukaryotic host cells and competing bacteria. An intracellular contractile tubular structure that bears functional homology with bacteriophage tails is pivotal for ejection of pathogenic effectors. Here, we present the 6 Å cryoelectron microscopy structure of the contracted Vibrio cholerae tubule consisting of the proteins VipA and VipB.

Homotypic interaction and amino acid distribution of unilaterally conserved transmembrane helices.

Formation of non-covalent functional complexes of integral membrane proteins is frequently supported by sequence-specific interaction of their transmembrane helices. Here, we aligned human single-span membrane proteins with orthologs from other eukaryotes. We find that almost half of the human single-span membrane proteins contain a transmembrane helix that exhibits significant non-random unilateral conservation.

Structure and function of the AAA+ nucleotide binding pocket.

Members of the diverse superfamily of AAA+ proteins are molecular machines responsible for a wide range of essential cellular processes. In this review we summarise structural and functional data surrounding the nucleotide binding pocket of these versatile complexes. Protein Data Bank (PDB) structures of closely related AAA+ ATPase are overlaid and biologically relevant motifs are displayed.