Linear Counterparts Research Articles

Rapid, Controlled Branching Polymerization of Cyanoacrylate via Pathway-Enabled, Site-Specific Branching Initiation.

Controlled branched structures remain a key synthetic limitation for monomeric tissue adhesives because their on-site polymerization that enables adhesion formation requires rapid kinetics, high conversion, and straightforward setup. In this context, site-specific branching initiation by using evolmers is potentially effective for structural control; however, the efficiency and kinetics in current reaction setups persists to be a major challenge. In this paper, an evolmer induces a controlled branching polymerization of cyanoacrylate amid the high monomer reactivity useful in rapid adhesion. The contrasting reactivities between the vinyl and the initiating groups in the evolmer molecule generate a kinetic pathway that favors a control-enabling branching mechanism. Through density functional theory calculations, the reaction pathway toward branching is shown to kinetically favor site-specific initiation by six orders of magnitude than the route toward non-specificity. Reaction monitoring confirms the branching polymerization after the polymerization with the evolmer forms a more compact structure than the linear counterpart. Control of branching density is demonstrated in rapid polymerizations within minutes and in polymerizations completed in an instant. These results provide a template for achieving site-specific branching initiation during adhesion formation and, broadly, where conditions for kinetic control are necessary.

Six lectures on linearized neural networks

Abstract This tutorial examines what can be learnt about the behavior of multi-layer neural networks from the analysis of linear models. While there are important gaps between neural networks and their linear counterparts, many useful lessons can be learnt by studying the latter. A few preliminary remarks, before diving into the math: • We will not assume specific background in machine learning, let alone neural networks. On the other hand, we will assume some graduate-level mathematics, in particular probability theory (however, we will refer to the literature for complete proofs.) • Some of the notations that are used throughout the text will be summarized in appendix A. • We will keep bibliographic references in the main text to a minimum. A short guide to the literature is given in appendix B.

Efficient Polymeric Nanoparticle Gene Delivery Enabled Via Tri- and Tetrafunctional Branching.

Poly(β-amino ester) (PBAE) nanoparticles (NPs) show great promise for nonviral gene delivery. Recent studies suggest branched PBAEs (BPBAEs) offer advantages over linear counterparts, but the effect of polymer structure has not been well investigated across many chemical constituents. Here, a library of BPBAEs was synthesized with tri- and tetrafunctional branching. These polymers self-assemble with DNA to form highly cationic, monodisperse NPs with notably small size (∼50 nm). Optimal transfection occurred with polymer structures that featured moderate PBAE branching, enabling complete DNA encapsulation, rapid NP uptake, and robust expression at low DNA doses and polymer amounts. Optimized NPs enabled efficient DNA delivery to diverse cell types in vitro while maintaining high cellular viability, demonstrating significant improvements over a well-performing linear PBAE counterpart. BPBAEs also facilitated efficient mRNA and siRNA delivery, highlighting the versatility of these structures and demonstrating the broad utility of BPBAE NPs as vectors for nucleic acid delivery.

An investigation of the relationship between long bone measurements and stature: Implications for estimating skeletal stature in subadults.

The present study introduces new regression formulae that address several challenges of current subadult stature estimation methods by 1) using a large, contemporary, cross-sectional sample of subadult skeletal remains; 2) generating regression models using both lengths and breadths; 3) utilizing both linear and nonlinear regression models to accommodate the nonlinear shape of long bone growth; and 4) providing usable prediction intervals for estimating stature. Eighteen long bone measurements, stature, and age were collected from computed tomography images for a sample of individuals (n = 990) between birth and 20 years from the United States. The bivariate relationship between long bone measurements and stature was modeled using linear and nonlinear methods on an 80% training sample and evaluated on a 20% testing sample. Equations were generated using pooled-sex samples. Goodness of fit was evaluated using Kolmogorov-Smirnov tests and mean absolute deviation (MAD). Accuracy and precision were quantified using percent testing accuracy and Bland-Altman plots. In total, 38 stature estimation equations were created and evaluated, all achieving testing accuracies greater than 90%. Nonlinear models generated better fits compared to linear counterparts and generally produced smaller MAD (3.65 - 15.90cm). Length models generally performed better than breadth models, and a mixture of linear and nonlinear methods resulted in highest testing accuracies. Model performance was not biased by sex, age, or measurement type. A freely available, online graphical user interface is provided for immediate use of the models by practitioners in forensic anthropology and will be expanded to include bioarchaeological contexts in the future.

Validating Small-Molecule Force Fields for Macrocyclic Compounds Using NMR Data in Different Solvents.

Macrocycles are a promising class of compounds as therapeutics for difficult drug targets due to a favorable combination of properties: They often exhibit improved binding affinity compared to their linear counterparts due to their reduced conformational flexibility, while still being able to adapt to environments of different polarity. To assist in the rational design of macrocyclic drugs, there is need for computational methods that can accurately predict conformational ensembles of macrocycles in different environments. Molecular dynamics (MD) simulations remain one of the most accurate methods to predict ensembles quantitatively, although the accuracy is governed by the underlying force field. In this work, we benchmark four different force fields for their application to macrocycles by performing replica exchange with solute tempering (REST2) simulations of 11 macrocyclic compounds and comparing the obtained conformational ensembles to nuclear Overhauser effect (NOE) upper distance bounds from NMR experiments. Especially, the modern force fields OpenFF 2.0 and XFF yield good results, outperforming force fields like GAFF2 and OPLS/AA. We conclude that REST2 in combination with modern force fields can often produce accurate ensembles of macrocyclic compounds. However, we also highlight examples for which all examined force fields fail to produce ensembles that fulfill the experimental constraints.

Electronic Structures and Spectra of Donor-Acceptor Conjugated Oligomers.

Narrow band gap donor-acceptor conjugated polymers present excellent paradigms in photonics and optoelectronics due to their chemical tunability, correlated electronic structures, and tunable open-shell electronic configurations. However, rational design for enhancing the properties of these molecular systems remains challenging. In this study, we employed density functional theory (DFT) calculations to investigate prototypical narrow band gap donor-acceptor conjugated oligomers, consisting of alternating cyclopentadithiophene (CPDT) donors paired with benzothiadiazole (BT), benzoselenadiazole (BSe), benzobisthiadiazole (BBT), and thiadiazoloquinoxaline (TQ) acceptors. Analyses of structures, singlet-triplet gaps, and absorption spectra of oligomers with up to ten repeat units have shown that when incorporating the BT, BSe, and TQ acceptors, the backbone curvature resulted in spiral structures that were energetically favored over their linear counterparts, causing differences in the calculated circular dichroism spectra. Oligomers with BBT-based acceptors preferred, however, a linear geometry, consistent with an open-shell electronic structure. Calculated singlet-triplet splittings demonstrated the importance of long chains and specific structures for consistency with the experiment, while effects of the solvent were also quantified. Based on the predicted low-energy conformations, one-photon absorption spectra for the considered oligomers have shown that using the Tamm-Dancoff approximation within time-dependent DFT for the large systems offers good agreement with the first absorption maxima in measured experimental spectra, thus validating the method for large donor-acceptor oligomers. Natural transition orbital analyses provided insights into the excited-state characteristics. Two-photon absorption maxima were accurately predicted, but the cross-sections were overestimated or underestimated, as dependent on the level of theory employed, to be addressed in future work.

Towards enhanced metamaterials via shape memory alloy-embedded nonlinear resonators

Standard acoustic metamaterials create an attenuation around specific frequency bands. Finite structures, with distinct boundary conditions and a limited number of unit cells, present less attenuation and narrower bands than those predicted by idealized infinite systems. A critical engineering goal is enhancing performance to motivate practical applications. To that aim, this work incorporates shape memory alloys into a quasi-zero stiffness resonator design, allowing the tuning of each cell's internal resonance. Such a feature enables the system reconfiguration to achieve different purposes, from following a disturbance frequency fluctuation to realizing graded nonlinear metamaterials. While the former can work under an adaptive framework, the latter can result in time-invariant locally resonant metamaterials with wideband vibration attenuation. The proposed design combines a frame that axially compresses an SMA beam in the vicinity of its buckling. The critical buckling force changes by thermally activating the SMA, affecting the residual stiffness, hence the unit cell resonant frequency. The unit cell concept is developed analytically and via finite elements, then built and validated experimentally. The promising results indicate the viability of the proposed concept. Preliminary numerical simulations and experiments show the advantages of the proposed smart resonator over a linear time-invariant counterpart.

Long in vivo circulating nanomicelles formed by sharp-contrast Janus star polymers derived from β-cyclodextrin grafted with lipids and polyzwitterions

Amphiphilic block polymers have the ability to self-assemble and form nanomicelles, which have been extensively studied as nanocarriers for improving the bioavailability and biodistribution of chemotherapeutic drugs while reducing systemic toxicity. However, polymer micelles often face issues with poor stability in the bloodstream, leading to a short circulation time and leakage of the payload. Here, this work reports a rational design of a sharp-contrast Janus star polymer (SJSP) consisting of multiple arms of superhydrophobic lipid moieties and superhydrophilic polyzwitterion chains attached to a β-cyclodextrin core. The SJSP polymer forms nanomicelles possessing a stable core and a controllable and dense stealth shell that effectively protects them in the bloodstream, preventing payload leakage and blood protein adsorption. It is demonstrated that the hydrophobic/hydrophilic balance can be optimized to achieve strong micellar assembly by adjusting the number of lipid and polyzwitterion arms. The SJSP micelle system shows significantly longer blood circulation time in vivo compared to linear counterparts and other available amphiphilic block copolymer micelle systems. Therefore, the SJSP micelle design offers a promising strategy for developing nanocarriers with potential for translational applications in vivo.

Broadband and robust vibration reduction in lattice-core sandwich beam with 3D-printed QZS resonators

The demand for lightweight lattice-core sandwich structures that exhibit superior mechanical and dynamic properties is widespread in many devices. This paper presents a lattice-core sandwich beam (LSB) with an embedded array of quasi-zero-stiffness (QZS) resonators, referred to as Q-LSB. This research distinguishes itself from existing studies on metamaterial structures with QZS resonators by investigating the nonlinear stiffness of QZS resonators and the damping of a soft three-dimensional (3D) printing material. The objective is to achieve efficient and robust vibration reduction beyond the band gap of its linear counterpart. We investigate the beam vibration using both experimental and numerical methods. The experimental results demonstrate that the resonators can entail significant vibration reduction in a wide frequency range, covering the first three eigenmodes of the host LSB. Furthermore, the reduction effect improves as the excitation level increases within the tested excitation range, highlighting the structure’s robustness against the excitation amplitude. A numerical model based on a dynamically equivalent homogenization method and the finite element method is established and experimentally validated. Subsequently, the numerical parametric results reveal that the broadband vibration reduction is due to the damping effect, while the robust vibration reduction effect is attributed to the nonlinear stiffness of the resonators.

Analytical Methods to Evaluate RNA Circularization Efficiency.

Circular RNAs (circRNAs) have emerged as pivotal players in RNA therapeutics. Unlike linear counterparts, circRNAs possess a closed-loop structure, conferring them with enhanced stability and resistance to degradation. Ribozyme-based strategy stands out as the predominant method for synthetic circRNA production, by precisely cleaving and promoting the formation of a covalent circular structure. However, there is still a lack of analytical methods that can provide high-throughput and quantitative analysis to facilitate the circRNA vector engineering process. In the report, we detail analytical methods to characterize and evaluate ribozyme-based RNA circularization efficiency. Our approach will capture the attention of researchers interested in optimizing RNA circularization efficiency, as well as those focused on exploring key elements for ribozyme catalytic activity.

Spontaneous Symmetry Breaking in Diffraction.

We demonstrate spontaneous symmetry breaking in the diffraction of a laser-driven grating with memory in its nonlinear response. We observe, experimentally and theoretically, asymmetric diffraction even when the grating and illumination are symmetric. Our analysis reveals how diffracted waves can spontaneously acquire momentum parallel to the lattice vector in quantities unconstrained by the grating period. Our findings point to numerous opportunities for imaging, sensing, and information processing with nonlinear periodic systems, which can leverage a much richer diffractive response than their linear counterparts.

Back to the Origin: Mechanisms of circRNA-Directed Regulation of Host Genes in Human Disease.

Circular RNAs (circRNAs) have been shown to be pivotal regulators in various human diseases by participating in gene splicing, acting as microRNA (miRNA) sponges, interacting with RNA-binding proteins (RBPs), and translating into short peptides. As the back-splicing products of pre-mRNAs, many circRNAs can modulate the expression of their host genes through transcriptional, post-transcriptional, translational, and post-translational control via interaction with other molecules. This review provides a detailed summary of these regulatory mechanisms based on the class of molecules that they interact with, which encompass DNA, mRNA, miRNA, and RBPs. The co-expression of circRNAs with their parental gene productions (including linear counterparts and proteins) provides potential diagnostic biomarkers for multiple diseases. Meanwhile, the different regulatory mechanisms by which circRNAs act on their host genes via interaction with other molecules constitute complex regulatory networks, which also provide noticeable clues for therapeutic strategies against diseases. Future research should explore whether these proven mechanisms can play a similar role in other types of disease and clarify further details about the cross-talk between circRNAs and host genes. In addition, the regulatory relationship between circRNAs and their host genes in circRNA circularization, degradation, and cellular localization should receive further attention.

Tuning residual stresses in welded structures by exploiting bio‐inspired suture interfaces

AbstractNature offers a valuable source of inspiration when designing optimized structures. For instance, when two or more shells are joined during growth processes, Nature prefers to exploit interlocking paradigms to enhance the strength of the bond—cranial sutures are one example. Mimicking this distinctive characteristic when welding thin metallic elements may offer some structural benefits. The present study theoretically investigates the possibility of mitigating the detrimental tensile residual stress that always originated by welding processes, by exploiting Computational Welding Mechanics. Specifically, two plates joined by laser welding following sinusoidal paths (i.e., wave‐like), alongside a linear one, will be studied and compared. Thanks to the distinctive temporal and spatial heat distributions of sinusoidal welding, both welding stress and strain develop in dissimilar ways compared with linear path welding—this is reflected to the resulting weldment distortion too. The results show that geometrically optimized sinusoidal welding can effectively reduce residual stress magnitudes compared with the linear configuration counterpart. The implications of these findings are of particular interest when dealing with the structural performance of welded structures, especially in fatigue contexts.

Miktoarm Star-polypept(o)ide-Based Polyion Complex Micelles for the Delivery of Large Nucleic Acids.

Miktoarm star polymers exhibit a captivating range of physicochemical properties, setting them apart from their linear counterparts. This study devised a synthetic pathway to synthesize cationic miktoarm stars utilizing polypept(o)ides (PeptoMiktoStars), comprising 3 or 6 polysarcosine (pSar) arms (AB3×100, AB6×50, overall 300) for shielding and a cross-linkable poly(S-ethylsulfonyl-l-homocysteine) (pHcy(SO2Et)20) block and a poly(l-lysine) ((pLys)20) block for nucleic acid complexation. Precise control over the DPn and narrow molecular weight distributions (D̵ ≈ 1.2) were achieved for both structures. Both PeptoMiktoStars efficiently complexed mRNA and pDNA into polyion complex micelles (PICMs). AB6-PICMs provided modest (mRNA) to high (pDNA) stability against glutathione and heparin sulfate (HS), while even cross-linked AB3-PICMs were susceptible to HS. All PICMs delivered pDNA and mRNA into D1 cells (over 80%) and Jurkat T cells (over 50%) in vitro. Despite payload- and cell-dependency, AB3 showed overall higher transfection efficiency, while AB6 demonstrated better shielding and enhanced stability.

Sustainable chitin-derived elastomers via grafting strategy with tunable mechanical and adhesion properties

With increasing environmental awareness and the pursuit of sustainable development goals, environmentally friendly sustainable thermoplastic elastomers (TPEs) derived from natural resources are highly desired to replace traditional TPEs. However, preparing sustainable TPEs with high mechanical properties and multifunctionality from biobased feedstocks remains a significant challenge. In this work, a series of chitin-graft-poly(acrylamide-co-2-ethylhexyl acrylate) (Chitin-g-P(AM-co-EHA)) copolymers were synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerization. The tensile strength of Chitin-g-P(AM-co-EHA) copolymers can be tuned over a wide range from 1.0 to 7.3 MPa by adjusting the chitin and PAM contents. Benefiting from the brush-like architecture, Chitin-g-P(AM-co-EHA) copolymer exhibits improved mechanical properties over its linear counterparts. Moreover, these Chitin-g-P(AM-co-EHA) copolymers show good adhesion performance on different substrates. The shear strength can achieve 7.5 MPa for Chitin0.8-PAM50, which is high enough for commercial applications. The combination of chitin and grafting strategy can promote the development of strong chitin-based sustainable elastomers. This approach can be further utilized to design novel high-performance biobased elastomers and adhesives derived from natural resources.

Assessing the circularity and sustainability of circular carpets — a demonstration of circular life cycle sustainability assessment

Abstract Purpose Robust assessments are needed to identify the best circular economy (CE) approaches related to their contribution to achieving a CE by simultaneously considering the complexity of the three pillars of sustainability (environmental, economic, social). In this regard, the circular life cycle sustainability assessment (C-LCSA) framework was recently developed. This study aimed to demonstrate its applicability and capability of identifying trade-offs and interlinkages between the different dimensions using a case study of different CE approaches to carpet tiles. Methods C-LCSA integrates circularity and life cycle sustainability assessments (LCSA). Thus, this study applied the material circularity indicator (MCI) in parallel to life cycle assessment (LCA), life cycle costing (LCC), and social life cycle assessment (S-LCA). The last technique was applied as social hotspot assessment. Five CE approaches of carpet tiles produced in the US, including strategies like reducing the consumption of primary materials through recycled and bio-based feedstock or replacing carpet tiles for a longer overall service life, as well as recycling, were assessed and compared to their mainly linear counterpart. Results and discussion The study revealed that recycling carpet tiles containing recycled and bio-based materials at the end-of-life (EoL) resulted in the lowest global warming potential (8.47 kg CO2 eq.) and the highest circularity (MCI value of 0.76, with 1 indicating the maximum level of circularity) compared to the other scenarios. However, this scenario had a trade-off with a higher acidification potential (0.039 kg SO2 eq.) and higher costs (US$19.98) compared to the disposal scenario. On the other hand, the scenario using primary, non-bio-based materials in production and disposing of the carpet tiles at their EoL performed the worst in circularity (MCI value of 0.11) and implied high environmental impacts while being more cost-effective (US$10.27). Conclusions C-LCSA transparently revealed interlinkages in terms of circularity and the overall sustainability performance of different CE approaches. While no significant differences in terms of social hotspots were identified, approaches associated with a higher circularity and improved environmental performance in most impact categories tended to result in higher costs. This emphasized the need for individual and holistic assessments of the new CE approach to identify and address trade-offs. To enhance and foster C-LCSA in academia and industry, further studies applying the framework to different sectors are encouraged.

Cross-linking enhances the performance of four-electron carbonylpyridinium based polymers for lithium organic batteries.

Design and integration of multiple redox-active organic scaffolds into tailored polymer structures to enhance the specific capacity and cycling life is a long-term research goal. Inspired by nature, we designed and incorporated a 4-electron accepting dicarbonylpyridinium redox motif into linear (DBMP) and cross-linked polymer (TBMP) structures. Benefiting from the suppressed solubility and higher electronic conductivity, the cross-linked TBMP based electrode exhibits improved cycling stability and higher specific capacity than the linear counterpart. After 4000 cycles at 1 A g-1, TBMP can maintain a high capacity of 252 mA h g-1, surpassing the performance of many reported organic cathodes. The structural evolution and reaction kinetics during charge and discharge have been investigated in detail. This study demonstrates that cross-linking is an effective strategy to push the bio-derived carbonylpyridinium materials for high performance LOBs.

Integer programming using a single atom

Integer programming (IP), as the name suggests is an integer-variable-based approach commonly used to formulate real-world optimization problems with constraints. Currently, quantum algorithms reformulate the IP into an unconstrained form through the use of binary variables, which is an indirect and resource-consuming way of solving it. We develop an algorithm that maps and solves an IP problem in its original form to any quantum system possessing a large number of accessible internal degrees of freedom that are controlled with sufficient accuracy. This work leverages the principle of superposition to solve the optimization problem. Using a single Rydberg atom as an example, we associate the integer values to electronic states belonging to different manifolds and implement a selective superposition of different states to solve the full IP problem. The optimal solution is found within a few microseconds for prototypical IP problems with up to eight variables and four constraints. This also includes non-linear IP problems, which are usually harder to solve with classical algorithms when compared to their linear counterparts. Our algorithm for solving IP is benchmarked by a well-known classical algorithm (branch and bound) in terms of the number of steps needed for convergence to the solution. This approach carries the potential to improve the solutions obtained for larger-size problems using hybrid quantum–classical algorithms.

Imaging and quantification of human and viral circular RNAs.

We present a robust approach for cellular detection, imaging, localization, and quantification of human and viral encoded circular RNAs (circRNA) using amplified fluorescence in situ hybridization (ampFISH). In this procedure, a pair of hairpin probes bind next to each other at contiguous stretches of sequence and then undergo a conformational reorganization which initiates a target-dependent hybridization chain reaction (HCR) resulting in deposition of an amplified fluorescent signal at the site. By harnessing the capabilities of both ampFISH and single-molecule FISH (smFISH), we selectively identified and imaged circular RNAs and their linear counterparts derived from the human genome, SARS-CoV-2 (an RNA virus), and human cytomegalovirus (HCMV, a DNA virus). Computational image processing facilitated accurate quantification of circular RNA molecules in individual cells. The specificity of ampFISH for circular RNA detection was confirmed through an in situ RNase R treatment that selectively degrades linear RNAs without impacting circular RNAs. The effectiveness of circular RNA detection was further validated by using ampFISH probes with mismatches and probe pairs that do not bind to the continuous sequence in their target RNAs but instead bind at segregated sites. An additional specificity test involved probes against the negative strands of the circular RNA sequence, absent in the cell. Importantly, our technique allows simultaneous detection of circular RNAs and their linear counterparts within the same cell with single molecule sensitivity, enabling explorations of circular RNA biogenesis, subcellular localization, and functions.

Coupled wave equations with monotone nonlinearity: existence of solution and controllability results

In this manuscript, we investigate a coupled semilinear system characterised by two wave equations in which the nonlinear function satisfies the monotonicity condition. Initially, the existence of a solution is established through the application of Schauder's fixed point theorem. Thereafter, the results pertaining to the exact controllability are demonstrated for two different cases by establishing a relation between the reachable set of the semilinear system and its linear counterpart. Additionally, an illustrative example is provided to showcase the practical relevance of our theoretical findings.