Conformal Shape Research Articles

Nonreducing Sugar Scaffold Enables the Development of Immunomodulatory TLR4-specific LPS Mimetics with Picomolar Potency.

Innate immune defense mechanisms against infection and cancer encompass the modulation of pattern recognition receptor (PRR)-mediated inflammation, including upregulation of various transcription factors and the activation of pro-inflammatory pathways important for immune surveillance. Dysfunction of PRRs-mediated signaling has been implicated in cancer and autoimmune diseases, while the overactivation of PRRs-driven responses during infection can lead to devastating consequences such as acute lung injury or sepsis. We used crystal structure-based design to develop immunomodulatory lipopolysaccharide (LPS) mimetics targeting one of the ubiquitous PRRs, Toll-like Receptor 4 (TLR4). Taking advantage of an exo-anomeric conformation and specific molecular shape of synthetic nonreducing β,β-diglucosamine, which was investigated by NMR, we developed two sets of lipid A mimicking glycolipids capable of either potently activating innate immune responses or inhibiting pro-inflammatory signaling. Stereoselective 1,1'-glycosylation towards fully orthogonally protected nonreducing GlcNβ(1↔1')βGlcN followed by stepwise assembly of differently functionalised phosphorylated glycolipids provided biologically active molecules that were evaluated for their ability to trigger or to inhibit cellular innate immune responses. Two LPS mimetics, identified as potent TLR4-specific inducers of the intracellular signaling pathways, serve as vaccine adjuvant- and immunotherapy candidates, while anionic glycolipids with TLR4-inhibitory potential hold therapeutic promise for the management of acute or chronic inflammation.

Nonreducing Sugar Scaffold Enables the Development of Immunomodulatory TLR4‐specific LPS Mimetics with Picomolar Potency

AbstractInnate immune defense mechanisms against infection and cancer encompass the modulation of pattern recognition receptor (PRR)‐mediated inflammation, including upregulation of various transcription factors and the activation of pro‐inflammatory pathways important for immune surveillance. Dysfunction of PRRs‐mediated signaling has been implicated in cancer and autoimmune diseases, while the overactivation of PRRs‐driven responses during infection can lead to devastating consequences such as acute lung injury or sepsis. We used crystal structure‐based design to develop immunomodulatory lipopolysaccharide (LPS) mimetics targeting one of the ubiquitous PRRs, Toll‐like Receptor 4 (TLR4). Taking advantage of an exo‐anomeric conformation and specific molecular shape of synthetic nonreducing β,β‐diglucosamine, which was investigated by NMR, we developed two sets of lipid A mimicking glycolipids capable of either potently activating innate immune responses or inhibiting pro‐inflammatory signaling. Stereoselective 1,1′‐glycosylation towards fully orthogonally protected nonreducing GlcNβ(1↔1′)βGlcN followed by stepwise assembly of differently functionalised phosphorylated glycolipids provided biologically active molecules that were evaluated for their ability to trigger or to inhibit cellular innate immune responses. Two LPS mimetics, identified as potent TLR4‐specific inducers of the intracellular signaling pathways, serve as vaccine adjuvant‐ and immunotherapy candidates, while anionic glycolipids with TLR4‐inhibitory potential hold therapeutic promise for the management of acute or chronic inflammation.

TEAM: Triangular-mEsh Adaptive and Multiscale proton spot generation method.

Proton therapy is preferred for its dose conformality to spare normal tissues and organs-at-risk (OAR) via Bragg peaks with negligible exit dose. However, proton dose conformality can be further optimized: (1) the spot placement is based on the structured (e.g., Cartesian) grid, which may not offer conformal shaping to complex tumor targets; (2) the spot sampling pattern is uniform, which may be insufficient at the tumor boundary to provide the sharp dose falloff, and at the same time may be redundant at the tumor interior to provide the uniform dose coverage, for example, due to multiple Coulomb scattering (MCS); and (3) the lateral spot penumbra increases with respect to the depth due to MCS, which blurs the lateral dose falloff. On the other hand, while (1) the deliverable spots are subject to the minimum-monitor-unit (MMU) constraint, and (2) the dose rate is proportional to the MMU threshold, the current spot sampling method is sensitive to the MMU threshold and can fail to provide satisfactory plan quality for a large MMU threshold (i.e., high-dose-rate delivery). This work will develop a novel Triangular-mEsh-based Adaptive and Multiscale (TEAM) proton spot generation method to address these issues for optimizing proton dose conformality and plan delivery efficiency. Compared to the standard clinically-used spot placement method, three key elements of TEAM are as follows: (1) a triangular mesh instead of a structured grid: the triangular mesh is geometrically more conformal to complex target shapes and therefore more efficient and accurate for dose shaping inside and around the target; (2) adaptive sampling instead of uniform sampling: the adaptive sampling consists of relatively dense sampling at the tumor boundary to create the sharp dose falloff, which is more accurate, and coarse sampling at the tumor interior to uniformly cover the target, which is more efficient; and (3) depth-dependent sampling instead of depth-independent sampling: the depth-dependent sampling is used to compensate for MCS, that is, with increasingly dense sampling at the tumor boundary to improve dose shaping accuracy, and increasingly coarse sampling at the tumor interior to improve dose shaping efficiency, as the depth increases. In the TEAM method the spot locations are generated for each energy layer and layer-by-layer in the multiscale fashion; and then the spot weights are derived by solving the IMPT problem of dose-volume planning objectives, MMU constraints, and robustness optimization with respect to range and setup uncertainties. Compared to the standard clinically-used spot placement method UNIFORM, TEAM achieved (1) better plan quality using <60% number of spots of UNIFORM; (2) better robustness to the number of spots; (3) better robustness to a large MMU threshold. Furthermore, TEAM provided better plan quality with fewer spots than other adaptive methods (Cartesian-grid or triangular-mesh). A novel triangular-mesh-based proton spot placement method called TEAM is proposed, and it is demonstrated to improve plan quality, robustness to the number of spots, and robustness to the MMU threshold, compared to the clinically-used spot placement method and other adaptive methods.

Strain in Hybrid Organic-Inorganic Metal Halide Perovskites Microstructures by Numerical Simulations.

Hybrid organic-inorganic metal halide perovskites (HOIPs) are promising materials for optoelectronics applications. Their optical and electrical properties can be controlled by strain engineering, that results from application of local elastic deformation or deposition on pre-patterned substrates acquiring a conformal 3D shape. Most interesting, their mechanical properties depend on their crystal structure, composition and dimensionality. We explore by numerical simulations the deformation of a selection of HOIPs comprising a broad range of elastic properties. We consider an axial symmetry with the formation of microdomes on flakes. Radial and vertical forces are considered, finding that the radial force is more effective to obtain large deformation. Large vertical displacement and strain is obtained for HOIPs with low stiffness. The layered nature of HOIPs, that are formed by inorganic layers of different thickness and organic spacers, is also investigated, revealing a non-monotonous trend with the proportion of inorganic to organic part.

Long-term follow-up demonstrates change in conformation shape of the focal choroidal excavation lesions

PurposeThis study aims to present long-term observation of 5 eyes with focal choroidal excavation (FCE), focusing on morphological changes in conformity of the lesion.MethodsA retrospective case series was conducted, including 5 eyes of 5 patients with FCE. The study utilized multimodal imaging including color fundus photography, optical coherence tomography (OCT), enhanced depth imaging OCT (EDI-OCT), fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), red free imaging, and OCT angiography.ResultsThe mean age at diagnosis was 51 ± 10.65 years, with a mean follow-up period 37 ± 13.59 months. All cases were unilateral, with 1 presenting FCE as an isolated lesion, and one patient exhibiting 2 FCEs in one eye. The mean choroidal thickness measured by EDI-OCT was 268.2 ± 63.39 μm in the affected eye. One patient displayed choroidal thickening and pachyvessels. Of the 5 eyes, one had conforming and 4 non-conforming FCE. We observed a conversion in conformity in all patients, with 4 cases transitioning from non-conforming FCE to conforming type (3 spontaneously, 1 treatment-induced). In conforming FCE, a hyporeflective space appeared twice between neuroretina and retinal pigment epithelium with spontaneous regression.ConclusionWe observed change in shape from the conforming to non-conforming FCE and vice versa in all patients. We consider this small change in the hyporeflective space as non-pathologic and clinically insignificant.

Theoretical and experimental investigations on conformal polishing of microstructured surfaces

Microstructured surfaces play a pivotal role in various fields, notably in lighting, diffuser devices, and imaging systems. The performance of these components is intricately related to the accuracy of their shapes and the quality of their surfaces. Although current precision machining technologies are capable of achieving conformal shapes, the post-machining surface quality often remains uncertain. To appropriately address this challenge, this paper introduces a novel conformal polishing methodology, specifically designed to enhance the surface quality of microstructured surfaces while maintaining their shape accuracy. As part of the investigations, specialized tools, namely the damping tool and profiling damping tool, are methodically developed for polishing rectangular and cylindrical surfaces. A shape evolution model is established based on the simulation of individual microstructures, incorporating the concept of finite-slip on the microstructured surface. The findings reveal that principal stresses and velocities experience abrupt variations at the convex and concave corners of rectangular surfaces as well as at the ends of cylindrical surfaces. The numerically predicted surface shape errors after polishing demonstrate reasonably good agreement with experimental results such that their discrepancies are less than 1 μm. Additionally, this method is able to successfully eradicate pre-machining imperfections such as residual tool marks and burrs on the microstructured surfaces. The arithmetic roughness (Ra) of the rectangular surface is measured to be an impressively low 0.4 nm, whereas the cylindrical surface exhibits Ra = 6.2 nm. These results clearly emphasize the effectiveness of the conformal polishing method in achieving high-quality surface finishes.

Flexible dielectric spacer with tunable dielectric properties for metamaterial absorber application

The development of a flexible and robust metamaterial absorber is a great motivation for the new generation of microwave absorbers covering any conformal shape. Ceramic–polymer composites with variable dielectric constant within the microwave frequencies are proposed as a flexible middle dielectric spacer (MDS) layer to provide an additional degree of design freedom for metamaterial absorber applications. By varying the dielectric constant of the MDS layer, the resonance band of the metamaterial absorber can be tuned while retaining a low profile in addition to enhancing its electromagnetic performance for transverse magnetic (TM) polarized waves. To formulate these composites, tetragonal structured barium titanate (BaTiO3) powder is selected as an excellent candidate when mixed with elastomer polydimethylsiloxane (PDMS), resulting in high mechanical strength substrates. Experimentally, samples with a range of dielectric permittivity from 2.81 to 5.67 were obtained for a 0%–20% volume fill fraction of BaTiO3 in PDMS. The obtained dielectric permittivities are consistent with the Bruggeman effective medium theory. Utilizing an optimized composition (10% BaTiO3), resulting in = 4 substrate, an X-band flexible absorber is designed and fabricated to absorb more than 90% of incident electromagnetic waves within a frequency band of 8.16–12.12 GHz.

Reinforcement Learning Powered Station Parameter Optimized Radiation Therapy (SPORT): A Novel Treatment Planning and Beam Delivery Technique

Conventional intensity modulated radiation therapy (IMRT) with a typical 5-20 fixed beams often does not provide sufficient angular sampling required for conformal dose shaping, whereas current volumetric modulated arc therapy (VMAT) discretizes the angular space into equally spaced control points without considering the differential need for intensity modulation of different angles, leading to undersampling at some angles while oversampling at some other angles. Our goal is to develop a node or station parameter optimized radiation therapy (SPORT) strategy with simultaneously optimized angular sampling and beam modulation by leveraging state-of-the-art reinforcement learning and the unique capability of modern digital LINACs in dose delivery through programmable nodal points. We developed a SPORT optimization framework, in which, the process of programming control points (or station parameters) was formulated as a stochastic dynamic programming problem, which was solved by a reinforcement learning-based algorithm. On-policy reinforcement learning method, namely, state-action-reward-state-action (SARSA) was integrated with deep convolutional neural network to predict station parameters by utilizing the patient's anatomical structures meanwhile considering the delivery capability of a typical digital LINAC machine. Here, the deep convolutional neural network estimated the state-action value by using the quality of the plan with current station parameters when a next potential station parameter was selected. The state-action value was then updated by SARSA learning. The quality of the plan was quantified by dosimetry constraints. The model was assessed by a retrospective study on a cohort of patients underwent head-and-neck radiation therapy. Dosimetric analysis and delivery efficiency comparisons were used to evaluate the performance of the proposed framework. Our model was used to generate 16 plans unseen in the original training set. All the plans predicted by our model achieved better dose distributions without violating clinical planning constraints. Moreover, instead of using 4 full standard arcs in the original clinically used plans obtained via manual optimization, the predicted plans only used one full standard arc (about 178 control points) plus boost from a few sub-arcs (less than 30 degrees of gantry angles), which significantly improved the efficiency of the beam delivery. We are in the process of integrating the sub-arcs into the full arc by considering the programmable capability of modern LINACs. We demonstrated that a machine learning-based SPORT framework capable of optimizing the spatial sampling and beam modulation simultaneously for modern radiation therapy. The framework not only significantly improves the quality and efficiency of beam delivery, but also has the potential to be incorporated into current clinical workflow to improve the efficiency of dose planning and delivery.

Unconstrained Piezoelectric Vascular Electronics for Wireless Monitoring of Hemodynamics and Cardiovascular Health.

The patient-centered healthcare requires timely disease diagnosis and prognostic assessment, calling for individualized physiological monitoring. To assess the postoperative hemodynamic status of patients, implantable blood flow monitoring devices are highly expected to deliver real time, long-term, sensitive, and reliable hemodynamic signals, which can accurately reflect multiple physiological conditions. Herein, an implantable and unconstrained vascular electronic system based on a piezoelectric sensor immobilized is presented by a "growable" sheath around continuously growing arterial vessels for real-timely and wirelessly monitoring of hemodynamics. The piezoelectric sensor made of circumferentially aligned polyvinylidene fluoride nanofibers around pulsating artery can sensitively perceive mechanical signals, and the growable sheath bioinspired by the structure and function of leaf sheath has elasticity and conformal shape adaptive to the dynamically growing arterial vessels to avoid growth constriction. With this integrated and smart design, long-term, wireless, and sensitive monitoring of hemodynamics are achieved and demonstrated in rats and rabbits. It provides a simple and versatile strategy for designing implantable sensors in a less invasive way.

Promoter-Controlled Synthesis and Conformational Analysis of Cyclic Mannosides up to a 32-mer.

Cyclodextrins are widely used as carriers of small molecules for drug delivery owing to their remarkable host properties and excellent biocompatibility. However, cyclic oligosaccharides with different sizes and shapes are limited. Cycloglycosylation of ultra-large bifunctional saccharide precursors is challenging due to the constrained conformational spaces. Herein we report a promoter-controlled cycloglycosylation approach for the synthesis of cyclic α-(1→6)-linked mannosides up to a 32-mer. Cycloglycosylation of the bifunctional thioglycosides and (Z)-ynenoates was found to be highly dependent on the promoters. In particular, a sufficient amount of a gold(I) complex played a key role in the proper preorganization of the ultra-large cyclic transition state, providing a cyclic 32-mer polymannoside, which represents the largest synthetic cyclic polysaccharide to date. NMR experiments and a computational study revealed that the cyclic 2-mer, 4-mer, 8-mer, 16-mer, and 32-mer mannosides adopted different conformational states and shapes.

Promoter‐Controlled Synthesis and Conformational Analysis of Cyclic Mannosides up to a 32‐mer

AbstractCyclodextrins are widely used as carriers of small molecules for drug delivery owing to their remarkable host properties and excellent biocompatibility. However, cyclic oligosaccharides with different sizes and shapes are limited. Cycloglycosylation of ultra‐large bifunctional saccharide precursors is challenging due to the constrained conformational spaces. Herein we report a promoter‐controlled cycloglycosylation approach for the synthesis of cyclic α‐(1→6)‐linked mannosides up to a 32‐mer. Cycloglycosylation of the bifunctional thioglycosides and (Z)‐ynenoates was found to be highly dependent on the promoters. In particular, a sufficient amount of a gold(I) complex played a key role in the proper preorganization of the ultra‐large cyclic transition state, providing a cyclic 32‐mer polymannoside, which represents the largest synthetic cyclic polysaccharide to date. NMR experiments and a computational study revealed that the cyclic 2‐mer, 4‐mer, 8‐mer, 16‐mer, and 32‐mer mannosides adopted different conformational states and shapes.

Beam Stabilization of Deformed Conformal Array Antenna Based on Physical- Method -Driven Deep Learning

The array antenna will be inevitably deformed affected by the motion of the communication system or other special requirements, which will reduce the original good radiation performance, such as the gain dropping, the side lobes increasing, and even the beam splitting. In order to cope with the beam deterioration caused by the array antenna’s deformation, it is necessary to quickly manipulate the amplitude and phase distribution according to the current conformal array shape to stabilize the beam. This paper proposes a physical-method-driven deep-learning-based (PMDL-based) fast beam stabilization algorithm for the antenna array deformation. Firstly, we theoretically analyze the radiation pattern synthesis of the conformal array with the arbitrary surface to design the corresponding physical method, and we verify the accuracy of the method by the calculated and simulated results. Then, the deep neural network driven by the physical method is designed integrated with the aforementioned radiation pattern synthesis, whose training process is given. Finally, a 1×16 array antenna is taken as an example to verify the validity of the beam stabilization algorithm when the designed array is deformed. The simulated and measured results both indicate that the gain dropping and the sidelobe level rising are respectively less than 1.5 dB and 2 dB by applying the proposed PMDL-based fast beam stabilization when the array antenna is deformed within the range of 100° of the normal vector of each array element, while the beam stabilization time is less than 1.0 ms (testing time).

The dimer and Ising models on Klein bottles

We study the dimer and Ising models on a finite planar weighted graph with periodic-antiperiodic boundary conditions, i.e., on a graph \Gamma in the Klein bottle \mathcal{K} . Let \Gamma_{mn} denote the graph obtained by pasting m rows and n columns of copies of \Gamma , which embeds in \mathcal{K} for n odd and in the torus \mathbb{T}^2 for n even. We compute the dimer partition function Z_{mn} of \Gamma_{mn} for n odd in terms of the well-known characteristic polynomial P of \Gamma_{12}\subset\mathbb{T}^2 together with a new characteristic polynomial R of \Gamma\subset\mathcal{K} . Using this result together with the work of Kenyon, Sun and Wilson, we show that in the bipartite case, this partition function has the asymptotic expansion \log Z_{mn}=mn\frac{\mathbf{f}_0}{2}+\mathsf{fsc}+o(1) for m , n tending to infinity and m/n bounded below and above, where \mathbf{f}_0 is the bulk free energy for \Gamma_{12}\subset\mathbb{T}^2 and \mathsf{fsc} is an explicit finite-size correction term. The remarkable feature of this later term is its universality : it does not depend on the graph \Gamma , but only on the zeros of P on the unit torus and on an explicit (purely imaginary) conformal shape parameter. A similar expansion is also obtained in the non-bipartite case, assuming a conjectural condition on the zeros of P . We then show that this asymptotic expansion holds for the Ising partition function as well, with \mathsf{fsc} taking a particularly simple form: it vanishes in the subcritical regime, is equal to \log(2) in the supercritical regime, and to an explicit function of the shape parameter at criticality. These results are in full agreement with the conformal field theory predictions of Blöte, Cardy and Nightingale.We study the dimer and Ising models on a finite planar weighted graph with periodic-antiperiodic boundary conditions, i.e., on a graph \Gamma in the Klein bottle \mathcal{K} . Let \Gamma_{mn} denote the graph obtained by pasting m rows and n columns of copies of \Gamma , which embeds in \mathcal{K} for n odd and in the torus \mathbb{T}^2 for n even. We compute the dimer partition function Z_{mn} of \Gamma_{mn} for n odd in terms of the well-known characteristic polynomial P of \Gamma_{12}\subset\mathbb{T}^2 together with a new characteristic polynomial R of \Gamma\subset\mathcal{K} . Using this result together with the work of Kenyon, Sun and Wilson, we show that in the bipartite case, this partition function has the asymptotic expansion \log Z_{mn}=mn\frac{\mathbf{f}_0}{2}+\mathsf{fsc}+o(1) for m , n tending to infinity and m/n bounded below and above, where \mathbf{f}_0 is the bulk free energy for \Gamma_{12}\subset\mathbb{T}^2 and \mathsf{fsc} is an explicit finite-size correction term. The remarkable feature of this later term is its universality : it does not depend on the graph \Gamma , but only on the zeros of P on the unit torus and on an explicit (purely imaginary) conformal shape parameter. A similar expansion is also obtained in the non-bipartite case, assuming a conjectural condition on the zeros of P . We then show that this asymptotic expansion holds for the Ising partition function as well, with \mathsf{fsc} taking a particularly simple form: it vanishes in the subcritical regime, is equal to \log(2) in the supercritical regime, and to an explicit function of the shape parameter at criticality. These results are in full agreement with the conformal field theory predictions of Blöte, Cardy and Nightingale.

Environmentally Ultrasensitive Fluorine Probe to Resolve Protein Conformational Ensembles by 19F NMR and Cryo-EM.

Limited chemical shift dispersion represents a significant barrier to studying multistate equilibria of large membrane proteins by 19F NMR. We describe a novel monofluoroethyl 19F probe that dramatically increases the chemical shift dispersion. The improved conformational sensitivity and line shape enable the detection of previously unresolved states in one-dimensional (1D) 19F NMR spectra of a 134 kDa membrane transporter. Changes in the populations of these states in response to ligand binding, mutations, and temperature correlate with population changes of distinct conformations in structural ensembles determined by single-particle cryo-electron microscopy (cryo-EM). Thus, 19F NMR can guide sample preparation to discover and visualize novel conformational states and facilitate image analysis and three-dimensional (3D) classification.

Computational Evaluation of N-Based Transannular Interactions in Some Model Fused Medium-Sized Heterocyclic Systems and Implications for Drug Design.

As part of a project on fused medium-sized ring systems as potential drugs, we have previously demonstrated the usefulness of Density Functional Theory (DFT) to evaluate amine nitrogen-based transannular interactions across the central 10-membered ring in the bioactive dibenzazecine alkaloid, protopine. A range of related hypothetical systems have been investigated, together with transannular interactions involving ring-embedded imino or azo group nitrogens and atoms or groups (Y) across the ring. Electrostatic potential energies mapped onto electron density surfaces in the different ring conformations were evaluated in order to characterise these conformations. Unexpectedly, the presence of sp2 hybridised nitrogen atoms in the medium-sized rings did not influence the conformations appreciably. The strength and type of the N…Y interactions are determined primarily by the nature of Y. This is also the case when the substituent on the interacting nitrogen is varied from CH3 (protopine) to H or OH. With Y = BOH, very strong interactions were observed in protopine analogues, as well as in rings incorporating imino or azo groups. Strong to moderate interactions were observed with Y = CS, CO and SO in all ring systems. Weaker interactions were observed with Y = S, O and weaker ones again with an sp3 hybridised carbon (Y = CH2). The transannular interactions can influence conformational preferencing and shape and change electron distributions at key sites, which theoretically could modify properties of the molecules while providing new or enhanced sites for biological target interactions, such as the H or OH substituent. The prediction of new strong transannular interaction types such as with Y = BOH and CS should be helpful in informing priorities for synthesis and other experimental studies.

Aero-structural optimization and actuation analysis of a morphing wing section with embedded selectively stiff bistable elements

Morphing wings provide a potential avenue to improve aerodynamic performance of aircraft operating at multiple design conditions. Nevertheless, morphing wing design is constrained by the mutually exclusive goals of high load-carrying capacity, low weight, and sufficient aerodynamic control authority via conformal shape adaptation. This trade-off can be addressed by exploiting the stiffness selectivity and shape “lock-in” properties enabled by using bistable beam-like elements within compliant structures. In this paper, we present an aero-structural optimization method to realize morphing structures with selective stiffness and shape “lock-in” capability from embedded bistable elements. We leverage an embeddable beam element with an invertible curved arch that provides stiffness selectivity and camber variation to the proposed rib geometry. Optimization objectives and constraints are designed to maximize the structure’s stiffness change and camber morphing “lock-in” effect when operating at two distinct flight conditions. Using the optimization results, we manufacture a wing section demonstrator with selective stiffness and “lock-in” morphing featuring two optimized ribs, a load-carrying skin made of a carbon reinforced laminate, Macro-Fiber Composite (MFC) actuators, and a servo-controlled mechanism for switching the bistable elements’ states. The power and energy requirements of actuating and holding a target deflection are experimentally measured and compared. The results show that the bistable elements can assist in holding a target deflection at a reduced energy cost. Finally, we test the experimental demonstrator in a low-speed wind tunnel demonstrating the load carrying capability and lift variation achieved from switching states.

Automated morphological phenotyping using learned shape descriptors and functional maps: A novel approach to geometric morphometrics.

The methods of geometric morphometrics are commonly used to quantify morphology in a broad range of biological sciences. The application of these methods to large datasets is constrained by manual landmark placement limiting the number of landmarks and introducing observer bias. To move the field forward, we need to automate morphological phenotyping in ways that capture comprehensive representations of morphological variation with minimal observer bias. Here, we present Morphological Variation Quantifier (morphVQ), a shape analysis pipeline for quantifying, analyzing, and exploring shape variation in the functional domain. morphVQ uses descriptor learning to estimate the functional correspondence between whole triangular meshes in lieu of landmark configurations. With functional maps between pairs of specimens in a dataset we can analyze and explore shape variation. morphVQ uses Consistent ZoomOut refinement to improve these functional maps and produce a new representation of shape variation, area-based and conformal (angular) latent shape space differences (LSSDs). We compare this new representation of shape variation to shape variables obtained via manual digitization and auto3DGM, an existing approach to automated morphological phenotyping. We find that LSSDs compare favorably to modern 3DGM and auto3DGM while being more computationally efficient. By characterizing whole surfaces, our method incorporates more morphological detail in shape analysis. We can classify known biological groupings, such as Genus affiliation with comparable accuracy. The shape spaces produced by our method are similar to those produced by modern 3DGM and to auto3DGM, and distinctiveness functions derived from LSSDs show us how shape variation differs between groups. morphVQ can capture shape in an automated fashion while avoiding the limitations of manually digitized landmarks, and thus represents a novel and computationally efficient addition to the geometric morphometrics toolkit.

Femtosecond laser surface modification of 4H-SiC improves machinability

The high brittleness and hardness are harmful to the machinability of silicon carbide (SiC). To improve machinability, femtosecond laser (fs laser) surface modification was conducted. The results of scratching test for modification surface showed the fluctuation of tangential force and coefficient of friction (COF) and the decrease of energy of acoustic emission peak. COF under various axial loads tends to be 0.2. The scratching profile has a conformal shape and deeper depth. Experiments elucidate that machinability is improved by fs laser surface modification due to surface decomposition and laser-induced periodic surface structures. Although fs laser processing was treated as cold processing to some extent, the heat-related phenomena were non-negligible in SiC processing. To reveal the dynamic multi-scale mechanism during fs laser modification, the multi-physics finite element model and the molecular dynamics simulations coupled with a two-temperature model were applied. Multi-scale simulation results revealed that the recoil flow has a high speed of >1.2 m/s and the peak temperature exceeds 8000 K, causing the spatter and heat affect zone. The high electronic temperature gradient is generated during irradiating, causing the subsurface void generation. Consequently, fs laser surface modification can improve machinability, but the heat effect and subsurface void should be cautioned.

The thermodynamic and kinetic aspects of midazolam ring closure from benzophenone to benzodiazepine form, its acid–base equilibria and aromaticity: a quantum-chemical study

The process of midazolam ring closure was studied from the thermodynamic and kinetic points of view by means of quantum-chemical methods. B3LYP/6–311 + + G(d,p) model was employed for gas phase and water environment (polarizable continuum model) calculations. It was concluded that the reaction rate determining step is the first step—carbinolamine formation from amine and carbonyl ends of the opened benzodiazepine ring. The Gibbs free energy of activation was calculated as 35.1 kcal/mol for gas- phase and 33.9 kcal/mol for water environment. Intrinsic reaction coordinate calculations were performed to verify that the transition state really connects the substrate and product. Thermodynamically, this reaction is endoergic with ΔG = 9.6 kcal/mol for gas phase and 10.0 kcal/mol for water environment. However, the next step—carbinolamine protonation with immediate water molecule loss is expected to be fast and activation barrierless, which enables further progress of the ring closure, despite the positive ΔG of the fist step. Next, the protonated imine undergoes deprotonation to final closed ring, pharmacologically active molecule of midazolam. The whole chain of reaction is exoergic with ΔG equal to − 5.6 kcal/mol for gas phase and − 7.7 kcal/mol for water environment. In order to understand the role of other than benzodiazepine/imidazole molecular fragments on the ring closure process, a model was build which contains only benzodiazepine and imidazole rings. The activation barrier for the carbinolamine formation of the model is similar to midazolam in the gas phase but higher by about 10 kcal/mol for water environment. The most interesting difference is however that for the model, the carbinolamine formation step is exoergic with ΔG equal to − 2.2 kcal/mol for gas phase and − 1.8 kcal/mol for water environment. This difference can be connected to complicated conformational shape of the midazolam molecule, which during the ring closure undergoes unfavorable deformations with accompanying rise of the energy of the molecule. The protonation sites for both midazolam and the model were also studied. In the case of midazolam, the preferred protonation site is the imidazole ring nitrogen atom, but in the case of the model it is the benzodiazepine ring nitrogen atom. The aromaticity of the 5- and 7-membered rings were analyzed using two aromaticity—HOMA and pEDA. It follows that larger stability of the cation protonated at the benzodiazepine ring is accompanied with substantial increase of the 7-ring aromaticity in the model of midazolam. The complexes of midazolam and its model with a water molecule were analyzed because they are needed for evaluation of the energy of the whole process of ring closure. In the case of midazolam, the water molecule preferentially connects to imidazole ring, but in the case of the model, complexes with both imidazole and benzodiazepine rings have similar stability.

Selection of Suitable Dielectric Substrate for Miniaturization of Microstrip Patch Antenna Using DGS Fractals

Background: Antennas size reduction with good performance characteristics is an essential part of designing a microstrip patch antenna (MPA) to select a suitable dielectric substrate. Methods: A conventional MPA is designed at 10GHz frequency, and later Minkowski fractal (1st iteration) defected ground structure (DGS) technique is applied for size reduction. The design is made to keep the radiation and reflection characteristics in contention. Results: A miniaturized MPA with 11% size reduction has been simulated using HFSS. The simulation results show the realization and selection of the substrate materials in the design process. Here, five different substrates are judiciously implemented and later compared. The comparison is made based on return loss, bandwidth, impedance, gain and efficiency Conclusion: We found a miniaturized MPA using the proposed first iteration of Minkowski fractal DGS. This MPA is suitable for X-band satellite communication and may be applied in government institutions, civil, military, monitoring weather, air traffic, defence tracking, maritime vessel traffic, etc., due to conformal and planar shape with reduced electrical length at 10GHz operating frequency