Single Bead Research Articles

From simple to complex: Reconstructing all-atom structures from coarse-grained models using cg2all

In this issue of Structure, Heo and Feig present cg2all, a novel deep-learning model capable of efficiently predicting all-atom protein structures from coarse-grained (CG) representations. The model maintains high accuracy, even when the CG model is simplified to a single bead per residue, and has a number of promising applications.

Initial experiments to regenerate the surface of plasma-facing components by wire-based laser metal deposition

Plasma-facing components (PFC) in nuclear fusion reactors are exposed to demanding conditions during operation. The combination of thermal loads, plasma exposure as well as neutron induced damage and activation limits the number of materials suitable for this application. Due to its properties, tungsten (W) is foreseen as plasma-facing material (PFM) for the future DEMOnstration power plant. It is considered suitable due to its exceptionally high melting point, excellent thermal conductivity, low tritium retention and low erosion resistance during plasma exposure. But even tungsten armored PFCs have a limited lifetime due to, among other factors, surface erosion and the resulting thickness reduction of the armor material.In-situ local deposition of tungsten by means of additive manufacturing (AM) could counteract surface erosion and thus increase the service life span of PFCs. After evaluation of the potential AM processes qualified for this task, the wire-based laser metal deposition (LMD-w) process was selected as the most suitable process. First trials were conducted to examine if it is possible to reliably deposit tungsten onto tungsten substrate using the LMD-w process. In these first studies, single welding beads were generated, and in later experiments, entire layers were created from several welding beads which are arranged next to each other. To ensure reproducibility of the results, the substrate temperature was kept constant. Further experiments aimed at the elimination or minimization of problems such as oxidation, occurrence of balling defects, porosity, cracking, surface waviness and insufficient connection to the substrate. To increase the welding bead quality, the input parameters like laser power, deposition velocity, wire feed rate, inert gas flow, as well as the wire position were optimized. Furthermore, stacking of several layers, as well as the remelting of an already created layer, were carried out and investigated. This study represents the first steps in testing the feasibility of an in-situ surface regeneration concept for PFCs.

Use of Double Gelled Microspheres to Improve Release Control of Cinnamon-Loaded Nanoemulsions.

The use of nanoemulsions as encapsulation systems for active ingredients, such as cinnamon oil, has been studied. A surfactant based on polyoxyethylene glycerol esters from coconut/palm kernel oil has been used. The nanoemulsions were obtained by the two most commonly low-energy emulsification methods, the composition inversion phase (PIC) and the temperature inversion phase (PIT) methods. Nanoemulsions were successfully obtained by both methods, with very small droplet sizes (5-14 nm) in both cases, but a greater stability was observed when the PIT method was used. Nanoemulsions were encapsulated by external gelation using two different polysaccharides, alginate or chitosan, dissolved in the continuous phase of the nanoemulsion. Then, the nanoemulsion was dropped into a bath with a gelling agent. To improve the release control of cinnamon oil and avoid the burst effect, beads prepared with one of the polysaccharides were coated with the second polysaccharide and then gelled again. Double gelled beads were successfully obtained, the core with chitosan and the outer layer (shell) with alginate. SEM images showed the morphology of the single beads presenting high porosity. When the beads were coated, the porosity decreased because the second polysaccharide molecules covered the pre-existing pores. The smoother surface was obtained when this second layer was, in turn, gelled. The release patterns at pH = 2 and pH = 7 were studied. It was observed that the double gelled bead provided a more gradual release, but maintained approximately the same amount of final released oil. The release patterns were fitted to the Korsmeyer-Peppas model. The fitting parameters reflected the effect of the different coating layers, correlating with different diffusion mechanisms according to the bead core and shell materials.

Prediction of Melt Pool Dimension, Porosity Generation and Thermal Behavior of Ti-6Al-4V during Powder Bed Fusion at Various Scan Speeds and Laser Powers

The additive manufacturing technology called laser powder bed fusion enables to manufacture complex parts based on the fusion of a metallic powder layer by layer. In laser powder bed fusion, the produced component quality relies significantly on the parameters of the process. In this study, the powder titanium alloy Ti-6Al-4V is employed for the purpose of predicting the melt pool dimensions. To manufacture a single bead, several combinations of scan speed and laser power are used. This research studies the influence of the scan speed and the laser power on the melt pool dimensions and on the thermal history of a specified layer of powder. The results reveal that the geometry of the melt pool is considerably responsive to the scan speed and the laser power. Furthermore, unfavorable effects such as porosity defects are analyzed in detail. Suggestions are presented to employ optimal settings to prevent these undesirable outcomes. To validate the numerical results, a comparison with experimental results from the literature is carried out. Our numerical analysis proves a satisfactory correlation with the experimental investigations. The beam power and the scanning speed effects on the average temperature of the desired layers are discussed as well.

Heavy metal on stage: Making ion-exchange resin selective by peptide tetrazine-norbornene ligation

The challenge of recycling metal salt-contaminated wastewater is more relevant than ever, and cost-effective materials for specific ion-binding are required. A generic route to functionalize a macroporous polystyrene ion-exchange resin (LR-NH2) via chemoselective inverse electron-demand Diels-Alder (IEDDA) ligation is demonstrated. The resin is modified using accessible endo-/exo-5-norbornene-2-carboxylic acid (Nb-COOH) and a set of tetrazine-functionalized 5mer peptides based on sequence variations of the literature known Cu2+ binding domain HGGGW is employed for the IEDDA ligation. The resulting peptide-functionalized resins (LR-Pz-Peptides) are studied for Cu2+ binding to correlate ion-binding capacity with sequence properties by single bead analysis of metal amounts via inductively-coupled plasma mass spectrometry (ICP-MS). The complexation preferences are demonstrated and utilized for specific binding of Cu2+versus Ni2+ from 1:1 salt mixture as a model system. Enrichment factors of up to 305 could be realized, which might open the potential for applications in metal recycling or waste water purification.

Thermal and Microstructural Characterization of GRCop-84/In718 Bi-metallic Structures Additively Manufactured by Directed Energy Deposition

As a nickel-based super alloy, Inconel 718 (In718) has gained attention in different industries due to its excellent mechanical behavior under elevated temperatures. Nevertheless, its low thermal conductivity limits its application in many fields, such as thermal energy conversion and heat dissipation. GRCop-84, in contrast, is a copper-based alloy with extremely high thermal conductivity. Making bi-metallic structures with GRCop-84 may expand the thermal-related applications of Inconel 718. In this study, we investigate the thermal properties of In718/GRCop-84 bi-metallic structures fabricated by the directed energy deposition (DED) technique with different process parameters of laser power and scanning velocity. The resulting microstructures were analyzed through scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS), while the frequency-domain thermoreflectance (FDTR) technique has been adopted to acquire the thermal properties. The melt pool thermal conductivities were 50 W/m K on single bead samples and 100 W/m K on single-layer pads, significantly lower than that of bulk GRCop-84. EDS analysis reveals large deviations from standard GRCop-84 compositions inside the melt pool.

Using artificial neural networks to model single bead geometries processed by laser-wire direct energy deposition

Wire-feed laser additive manufacturing processes have gained researchers’ attention because of their potential to reduce material waste, guarantee accuracy, increase material quality and density, and produce a wide dimensional range of final products. Nevertheless, printing materials with desired geometrical properties of the beads is still challenging in such processes. This might be attributed to the need for more sufficient experimental data and precise modeling approaches. In this study, an architecture based on Artificial Neural Networks (ANNs) is developed to model the bead geometries (width, height, and area), considering the wire feed rate, laser power, and travel speed as process parameters. A design-of-experiment based on full factorial design is considered for processing single beads with a Fraunhofer coaxial wire-feed laser system. Inconel 625 wire with a diameter of 1.14 mm and stainless steel substrate are utilized as the experimental materials. Geometrical data is obtained using a laser scanner model RA-7525 SE with 0.026mm volumetric accuracy. The beads’ geometrical details are provided as the feeding data for the proposed ANN. For each bead, a length of 10 mm is considered to calculate the average geometrical parameters, which increases the accuracy of the dataset in comparison to the values acquired via a macroscopic picture of the cross-section of each weld bead. A variety of hyperparameters are chosen and compared regarding precision criteria, including Mean Square Error (MSE), to increase the model‘s accuracy. A train-test separation strategy is considered to evaluate the model‘s accuracy on independent data points. The outcome of this research is an ANN-based geometry prediction model that can be utilized to enhance the development of offline path planners and optimize process parameter selection for a precise geometry toward process control.

Impact of imlifidase treatment on immunoglobulins in an HLA-hypersensitized lupus nephritis patient with anti-SSA/SSB antibodies after kidney transplantation: A case report

Bacterial recombinant cysteine protease Ides (imlifidase, Idefirix®, Hansa Biopharma) is used to prevent humoral transplant rejection in highly HLA-sensitized recipients, and to control IgG-mediated autoimmune diseases. We report the case of a 51 years old woman suffering from lupus nephritis with end stage kidney disease, grafted for the second time and pre-treated with imlifidase. The patient was HLA-hypersensitized (calculated Panel Reactive Antibodies [Abs], cPRA>99 %) and has three preformed Donor Specific Antibodies (DSA). Circulating immunoglobulins were monitored at initiation (0, 6, 36, 72 and 96 h), and at Ab recovery one and two months following imlifidase injection. From baseline, the higher depletion was reported after 36h for total IgG (−75 %) and IgG subclasses (−87 % for IgG1, IgG2 and IgG3, -78 % for IgG4), while no significant impact on IgA and IgM was observed. Anti-SSA 60 kDa and anti-SSB auto-Abs quickly decreased after imlifidase injection (−96 % for both after 36 h) as well as post-vaccinal specific IgG (−95 % for tetanus toxoid, −97 % for pneumococcus and −91 % for Haemophilus influenzae Abs after 36 h). At the Ab recovery phase, total IgG and anti-SSA60/SSB Abs reached their initial level at two months. Regarding alloreactive Abs, anti-HLA Abs including the three DSA showed a dramatic decrease after injection with 100 % depletion from baseline after 36 h as assessed by multiplex single bead antigen assay, leading to negative crossmatches using both lymphocytotoxicity (LCT) and flow cell techniques. DSA rebound at recovery was absent and remained under the positivity threshold (MFI = 1000) after 6 months. The findings from this case report are that imlifidase exerts an early depleting effect on all circulating IgG, while IgG recovery may depend in part from imlifidase's capacity to target memory B cells.

One bead per residue can describe all-atom protein structures

Atomistic resolution is the standard for high-resolution biomolecular structures, but experimental structural data are often at lower resolution. Coarse-grained models are also used extensively in computational studies to reach biologically relevant spatial and temporal scales. This study explores the use of advanced machine learning networks for reconstructing atomistic models from reduced representations. The main finding is that a single bead per amino acid residue allows construction of accurate and stereochemically realistic all-atom structures with minimal loss of information. This suggests that lower resolution representations of proteins may be sufficient for many applications when combined with a machine learning framework that encodes knowledge from known structures. Practical applications include the rapid addition of atomistic detail to low-resolution structures from experiment or computational coarse-grained models. The application of rapid, deterministic all-atom reconstruction within multi-scale frameworks is further demonstrated with a rapid protocol for the generation of accurate models from cryo-EM densities close to experimental structures.

Single-cell trapping and retrieval in open microfluidics

Among various single-cell analysis platforms, hydrodynamic cell trapping systems remain relevant because of their versatility. Among those, deterministic hydrodynamic cell-trapping systems have received significant interest; however, their applications are limited because trapped cells are kept within the closed microchannel, thus prohibiting access to external cell-picking devices. In this study, we develop a hydrodynamic cell-trapping system in an open microfluidics architecture to allow external access to trapped cells. A technique to render only the inside of a polydimethylsiloxane (PDMS) microchannel hydrophilic is developed, which allows the precise confinement of spontaneous capillary flow in the open-type microchannel with a width on the order of several tens of micrometers. Efficient trapping of single beads and single cells is achieved, in which trapped cells can be retrieved via automated robotic pipetting. The present system can facilitate the development of new single-cell analytical systems by bridging between microfluidic devices and macro-scale apparatus used in conventional biology.

Structural and dynamical behavior of a vibrated granular system of hard-cubes

We study experimentally and by molecular dynamics simulations a quasi-two-dimensional granular system of cubic particles, confined in a squared box and kept in a dynamic steady state via vertical oscillations. First, we compared the dynamics of a single spherical bead and a cube. Remarkably, the trajectory of the cube shows characteristics of Brownian motion induced by the particle geometry, i.e. an erratic path generated by the collisions of the vertexes and edges of the cube with the vibrated plate; in contrast to the more predicted ballistic motion of a spherical bead. Upon the addition of more cubic particles to the system, the erratic motion is enhanced by multiple collisions, leading to a rich collective behavior. As the number of particles is increased, for instance, both the radial distribution function and the mean square displacement exhibit the qualitative features of the gas, liquid and crystalline-solid phases observed in thermally driven colloidal systems. The results obtained with experiments and simulations are in good agreement and, combined, suggest that a vibrated system of granular cubic particles provides a macroscopic ideal model of Brownian motion.

Investigating the behavior of the slow dynamic recovery at early times

Slow dynamics (SD), a type of non-classical nonlinear elastic behavior, is characterized by (i) a material softening due a minor mechanical conditioning and (ii) a subsequent slow recovery that approaches the original macroscopic elastic state. Early work in sandstones and other consolidated granular materials—and more recent work in unconsolidated granular materials—have found the recovery to be logarithmic-in-time, at least for seconds to hours after conditioning. However, other recent studies have observed recoveries in consolidated granular materials that deviate from log(time), particularly for early recovery times. This talk will present experimental investigations in to the nature of the SD recovery, especially at early times. The experimental venue will be the single bead system (a single bead confined between two large plates of a similar material) introduced previously. We will measure SD recoveries using multiple methods, such as Dynamic Acoustic Emission Testing (DAET) and Larsen Monitoring, to better compare our experiments with previous work. The effect of different conditioning mechanisms on the early time recovery will also be investigated. The presentation will conclude with some discussion of proposed mechanisms for slow dynamics.

Effect of temperature and substrate geometry on single aluminium weld bead geometry deposited by Wire Arc Additive Manufacturing: Proposition of an experimental procedure

Effect of temperature and substrate geometry on single aluminium weld bead geometry deposited by Wire Arc Additive Manufacturing: Proposition of an experimental procedure

Evaluation of Laser Lap Weldability between the Titanium Alloy Ti-6Al-4V and Aluminum Alloy 6060-T6

This work investigates laser weldability between non-ferrous dissimilar metallic materials, specifically the aluminum 6060-T6 alloy and titanium Ti-6Al-4V. These materials are used in several engineering applications, including aerospace. In a simple lap joint configuration, these were welded with a pulsed Nd:YAG laser, with direct incidence on the titanium piece. Preheating and post-weld heating were introduced to mitigate cracking issues. Based on the primary experiments, the main variables were the peak laser power, which varied between 60 and 70%, and the number of beads (a single bead and double beads). The quality of the welds was assessed via uniaxial tensile tests, subjecting the joint to shear loading. Additionally, SEM micrographs were obtained to analyze the quality of the fusion between the dissimilar alloys. The higher strength of the welded samples achieved was 90 MPa, which is close to the reported value for the aluminum base material. A fracture occurred near the weld bead in the heat-affected zone (HAZ). The observed microporosities and cracks explain the lower value as compared to the base material. Although these were mitigated through the thermal cycle strategy employed and the shielding gas, they were not entirely avoided.

Anisotropic fatigue crack propagation in wire arc additively manufactured 316L stainless steel

This work investigates the anisotropy with the fatigue crack propagation behaviour of wire arc additive manufactured 316L stainless steel. Tension and fatigue crack growth tests were conducted on specimens prepared along the traverse, build and diagonal directions from single bead wall deposits. Anisotropy was observed with the fatigue crack propagation behaviour and tensile properties. The fatigue crack growth rates were comparable along the build and traverse directions. However, the slowest crack growth rate was observed along the diagonal direction. The high ductility observed along the diagonal direction limits the crack growth rate.

Systematic Study of Wettability Alteration of Glass Surfaces by Dichlorooctamethyltetrasiloxane Silanization-A Guide for Contact Angle Modification.

To investigate the effects of wettability on multiphase flow in porous media, glass bead packs or micromodels are commonly used. Their wettability can be altered by the surface treatment method-silanization. Although silanization is widely used for glass wettability modification, comparable systematic approaches over a large range of geometries, treatment conditions, and measurement systems are scarce. In this work, dichlorooctamethyltetrasiloxane (Surfasil) treatment was systematically investigated, resulting in a guide for achieving a wide range of contact angles. Initially, the influence of the Surfasil solvent, treatment time, and Surfasil-to-solvent ratio was investigated on glass plates using the sessile drop method. By varying these variables, it was possible to achieve a wide range of comparable, repeatable, and stable contact angles, from approximately 20-95° for air-water systems. Due to the linear increase of contact angle with larger Surfasil exposure, either due to the time or concentration, contact angle tuning is possible until the critical point. Beyond the critical point of exposure, a system-specific plateau value is reached, independent of the approach. After establishing a clear relationship between the parameters and contact angles, the same treatment parameters were applied to single beads, micromodels, and beadpacks with heptane as the chosen solvent. Optical image analysis was used for the microchips, and micro CT data analysis was used for the bead packs. The treatment appeared to be transferable to all geometries, resulting in similar wetting conditions within the limitations of the measurements. It is concluded that a glass plate can be used as an analogue for obtaining the contact angle alteration trends for more complex porous media with similar compositions. Data analysis methods and surface roughness could have an effect on the obtained contact angle spread.

Towards a general and numerically efficient deposition model for wire-arc directed energy deposition

The prediction of deposition behaviour during the wire-arc directed energy deposition process is essential for optimizing process parameters and toolpath during the process planning phase. To this end, this paper presents a new framework for accurate and fast prediction of the stacking of weld beads for arbitrary substrate geometries. The prediction is split into two tasks: the footprint prediction, for which a data-driven approach based on a deep convolutional neural network is proposed; and the weld bead shape prediction, for which a numerical model based on the minimization of surface energy is developed. For each prediction tasks, the prediction approaches are compared against baseline models. An extensive dataset is created for training and evaluation of the models. Dataset generation, noise, training procedures, and evaluation metrics are discussed. The results demonstrate an accurate prediction capability, with a median accuracy of 0.1mm and 0.19mm for single weld bead prediction and end-to-end prediction, respectively. The average prediction time amounts to approximately 150ms per weld bead.

A novel cyclic peptide library immobilized on gel-type beads focusing on rapid construction and characterization for comprehensive drug discovery.

Medium sized molecules such as peptides and macrocycles have recently drawn much attention as potent sources of medicinal lead compounds, whereas the possibility of obtaining a practical drug from them remains limited. The present paper describes a concept of discovering novel medicinal targets or binding modes as well as lead compounds by the one-peptide-on-one-bead (OPOB) technology for comprehensive screening. The difficulty and problems in conventional drug discovery methods that generally deal with one predetermined target are considered. The building blocks used for the present libraries were selected based on previous results in development of peptidic drugs. Each constituent has the common structure of cyclic form prepared by disulfide of cysteinyl residues or thioether linkages, additionally a methionine residue was inserted for the site-specific rapid cleavage by cyanogen bromide to liberate the immobilized peptides allowing reliable characterization by MALDI-TOF-MS/MS without LC-purification. Thus, a high throughput construction method for cyclic peptide libraries as well as characterization of single bead are proposed for drug discovery.

The earliest Baltic amber in Western Europe

The occurrence of Baltic amber through Europe has traditionally been associated to the spread of the Bell Beaker culture during the 3rd millennium BC. In Iberia, this phenomenon is particularly noticeable in the southern half. Here we present an amber bead recovered in a Late Neolithic funerary cave (3634–3363 cal BC) from northeastern Iberia where more than 12 individuals had been buried. Fourier transform infrared spectroscopy results of four samples revealed their complete resemblance with Baltic succinite reference spectra. Despite being a single bead, this finding provides the earliest evidence for the arrival of Baltic amber to the Mediterranean and Western Europe, before the Bell Beaker phenomenon and more than a millennium earlier than traditionally thought. This finding has implications for our understanding of early exchange networks of exotic materials, and their associated social structures.

Tensile and Compression Strength Prediction and Validation in 3D-Printed Short-Fiber-Reinforced Polymers.

In the current study, a methodology is validated for predicting the internal spatially varying strength properties in a single 3D-printed bead composed of 13%, by weight, carbon-fiber-filled acrylonitrile butadiene styrene. The presented method allows for the characterization of the spatially varying microstructural behavior yielding a local anisotropic stiffness and strength that can be integrated in a finite element framework for a bulk estimate of the effective stiffness and strength. The modeling framework is presented with a focus on composite structures made from large area additive manufacturing (LAAM). LAAM is an extrusion-based process yielding components on the order of meters, with a typical raster size of 10 mm. The presented modeling methods are applicable to other short-fiber-reinforced polymer processing methods as well. The results provided indicate the modeling framework yields results for the effective strength and stiffness that align with experimental characterization to within ∼1% and ∼10% for the longitudinal compressive and tensile strength, respectively, and to within ∼3% and ∼50% for the longitudinal compressive and tensile stiffness, respectively.