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Background: Despite a proposed causal role for low-density lipoprotein cholesterol (LDL-C) in aortic stenosis (AS), randomized controlled trials of lipid-lowering therapy failed to prevent severe AS. We aimed to assess the impact on AS and peak velocity across the aortic valve conferred by lifelong alterations in LDL-C levels mediated by protein-disrupting variants in three clinically significant genes for LDL metabolism (LDLR, APOB, PCSK9). Methods: We utilized sequencing data and electronic health records from UK Biobank (UKB) and All of Us and magnetic resonance imaging data from UKB. We identified predicted protein-disrupting variants with the LOFTEE and AlphaMissense algorithms and evaluated their associations with LDL-C and peak velocity across the aortic valve (UK Biobank), as well as diagnosed AS and aortic valve replacement (UK Biobank + All of Us). Results: We included 421,049 unrelated participants (5,621 with AS) in UKB and 195,519 unrelated participants (1,087 with AS) in All of Us. Carriers of protein-disrupting variants in LDLR had higher mean LDL-C (UKB: +42.6 mg/dl, P=4.4e-237) and greater risk of AS (meta-analysis: odds ratio [OR] =3.52 [95% CI 2.39-5.20], P=2.3e-10) and aortic valve replacement (meta-analysis: OR=3.78 [95% CI 2.26-6.32], P=4.0e-7). Carriers of protein-disrupting variants in APOB or PCSK9 had lower mean LDL-C (UKB: -32.3 mg/dl, P<5e-324) and lower risk of AS (meta-analysis: OR=0.49 [0.31-0.75], P=0.001) and aortic valve replacement (meta-analysis: OR=0.54 [0.30-0.97], P=0.04). Among 57,371 UKB imaging substudy participants, peak velocities across the aortic valve were greater in carriers of protein-disrupting variants in LDLR (+12.2cm/s, P=1.6e-5) and lower in carriers of protein-disrupting variants in PCSK9 (-6.9cm/s, P=0.022). Conclusions: Rare genetic variants that confer lifelong higher or lower LDL-C levels are associated with substantially increased and decreased risk of AS, respectively. Early and sustained lipid-lowering therapy may slow or prevent AS development.

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The detection of the liquid-to-ice transition is an important challenge for many applications. In this paper, a method for multi-parameter characterization of the liquid-to-ice phase transition is proposed and tested. The method is based on the fundamental properties of bulk acoustic waves (BAWs). BAWs with shear vertical (SV) or shear horizontal (SH) polarization cannot propagate in liquids, only in solids such as ice. BAWs with longitudinal (L) polarization, however, can propagate in both liquids and solids, but with different velocities and attenuations. Velocities and attenuations for L-BAWs and SV-BAWs are measured in ice using parameters such as time delay and wave amplitude at a frequency range of 1-37 MHz. Based on these measurements, relevant parameters for Rayleigh surface acoustic waves and Poisson's modulus for ice are determined. The homogeneity of the ice sample is also detected along its length. A dual sensor has been developed and tested to analyze two-phase transitions in two liquids simultaneously. Distilled water and a 0.9% solution of NaCl in water were used as examples.

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Analytical devices for bacterial detection are an integral part of modern laboratory medicine, as they permit the early diagnosis of diseases and their timely treatment. Therefore, special attention is directed to the development of and improvements in monitoring and diagnostic methods, including biosensor-based ones. A promising direction in the development of bacterial detection methods is optical sensor systems based on colorimetric and fluorescence techniques, the surface plasmon resonance, and the measurement of orientational effects. This review shows the detecting capabilities of these systems and the promise of electro-optical analysis for bacterial detection. It also discusses the advantages and disadvantages of optical sensor systems and the prospects for their further improvement.

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Optically Variable Devices (OVDs) are widely used as security features in anti-counterfeiting efforts. OVDs enable the display of color dynamic effects that are easily interpreted by the user. However, obtaining these elements over large areas poses certain challenges in terms of efficiency. The paper presents a modified approach for manufacturing plasmonic type OVDs through dot-matrix technology, which is a standard origination step of security holograms. By adjusting the spatial filters in the optical scheme, it is possible to double the resolution of the recorded quasi-sinusoidal diffraction gratings. The experiments confirm the creation of diffraction gratings with frequencies from 1600 to 3500 lines per mm, which facilitates the production of plasmonic zero-order spectral filters. The paper shows how the transmission characteristics of the studied elements are affected by the geometric parameters of the diffraction grating, silver layer thickness, angle of incidence, and polarization of light. The results have shown that using the proposed method it is possible to obtain 1D or 2D structural color OVD-image on a large area - several square centimeters and more. High speed recording of such elements is provided: the exposure time was from 120 to 400 ms depending on the grating resolution for a 0.05 mm2 frame, the total printing time for the size of the 25×25 mm2 OVD was about 2.5 hours for a 1D element, and less than 3.5 hours for a 2D element. Thus, the proposed method and the OVD elements produced by it can be useful to designers of optical security elements as a simpler and faster alternative to electron-beam lithographic technologies.

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2,3,5,6-Tetramethyl-1,4-diisocyanobenzene (1), 1,4-diisocyanobenzene (2), and 1,4-dicyanobenzene (3) were co-crystallized with 1,3,5-triiodotrifluorobenzene (1,3,5-FIB) to give three cocrystals, 1·1,3,5-FIB, 2·2(1,3,5-FIB), and 3·2(1,3,5-FIB), which were studied by X-ray diffraction. A common feature of the three structures is the presence of I···Cisocyanide or I···Nnitrile halogen bonds (HaBs), which occurs between an iodine σ-hole and the isocyanide C-(or the nitrile N-) atom. The diisocyanide and dinitrile cocrystals 2·2(1,3,5-FIB) and 3·2(1,3,5-FIB) are isostructural, thus providing a basis for accurate comparison of the two types of noncovalent linkages of C≡N/N≡C groups in the composition of structurally similar entities and in one crystal environment. The bonding situation was studied by a set of theoretical methods. Diisocyanides are more nucleophilic than the dinitrile and they exhibit stronger binding to 1,3,5-FIB. In all structures, the HaBs are mostly determined by the electrostatic interactions, but the dispersion and induction components also provide a noticeable contribution and make the HaBs attractive. Charge transfer has a small contribution (<5%) to the HaB and it is higher for the diisocyanide than for the dinitrile systems. At the same time, diisocyanide and dinitrile structures exhibit typical electron-donor and π-acceptor properties in relation to the HaB donor.

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The acoustic waves of higher orders propagating in a layered structure consisting of a silicon plate coated with piezoelectric ZnO and/or AlN films were used for the development of a sensor with selective sensitivity to liquid viscosity η in the range of 1-1500 cP. In that range, this sensor possessed low sensitivity to liquid conductivity σ and temperature T in the ranges of 0-2 S/m and 0-55 °C, respectively. The amplitude responses insensitive to the temperature instead of the phase were used to provide the necessary selectivity. The sensor was based on a weak piezoactive acoustic wave of higher order. The volume of the probes sufficient for the measurements was about 100 µL. The characteristics of the sensors were optimized by varying the thicknesses of the structure layers, number of layers, wavelength, wave propagation direction, and the order of the acoustic waves. It was shown that in the case of the layered structure, it is possible to obtain practically the same selective sensitivity toward viscosity as for acoustic waves in pure ST, X quartz. The most appropriate waves for this purpose are quasi-longitudinal and Lamb waves of higher order with in-plane polarization. It was found that for various ranges of viscosity η = 1-20 cP, 20-100 cP, and 100-1500 cP, the maximum sensitivity of the appropriate wave is equal to 0.26 dB/cP, 0.087 dB/cP, and 0.013 dB/cP, respectively. The sensitivity of the waves under study toward the electric conductivity of the liquid is much less than the sensitivity to liquid viscosity. These two responses become comparable only for very small η < 2 cP. The waves investigated have shown no temperature responses in contact with air, but in the presence of liquid, they increase depending on liquid properties. The temperature dependence of liquid viscosity is measurable by the same sensors. The results obtained have shown the possibility of designing acoustic liquid viscosity sensors based on multilayered structures. The set of possible acoustic waves in layered structures possesses modified propagation characteristics (various polarization, phase velocities, electromechanical coupling coefficients, and attenuations). It allows choosing an optimal acoustic wave to detect liquid viscosity only.

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Copy number variants (CNVs) are major contributors to genetic diversity and disease. While standardized methods, such as the genome analysis toolkit (GATK), exist for detecting short variants, technical challenges have confounded uniform large-scale CNV analyses from whole-exome sequencing (WES) data. Given the profound impact of rare and de novo coding CNVs on genome organization and human disease, we developed GATK-gCNV, a flexible algorithm to discover rare CNVs from sequencing read-depth information, complete with open-source distribution via GATK. We benchmarked GATK-gCNV in 7,962 exomes from individuals in quartet families with matched genome sequencing and microarray data, finding up to 95% recall of rare coding CNVs at a resolution of more than two exons. We used GATK-gCNV to generate a reference catalog of rare coding CNVs in WES data from 197,306 individuals in the UK Biobank, and observed strong correlations between per-gene CNV rates and measures of mutational constraint, as well as rare CNV associations with multiple traits. In summary, GATK-gCNV is a tunable approach for sensitive and specific CNV discovery in WES data, with broad applications.

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In this work, a sensitive coating based on Langmuir-Blodgett (LB) films containing monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) with an immobilized glucose oxidase (GOx) enzyme was created. The immobilization of the enzyme in the LB film occurred during the formation of the monolayer. The effect of the immobilization of GOx enzyme molecules on the surface properties of a Langmuir DPPE monolayer was investigated. The sensory properties of the resulting LB DPPE film with an immobilized GOx enzyme in a glucose solution of various concentrations were studied. It has shown that the immobilization of GOx enzyme molecules into the LB DPPE film leads to a rising LB film conductivity with an increasing glucose concentration. Such an effect made it possible to conclude that acoustic methods can be used to determine the concentration of glucose molecules in an aqueous solution. It was found that for an aqueous glucose solution in the concentration range from 0 to 0.8 mg/mL the phase response of the acoustic mode at a frequency of 42.7 MHz has a linear form, and its maximum change is 55°. The maximum change in the insertion loss for this mode was 18 dB for a glucose concentration in the working solution of 0.4 mg/mL. The range of glucose concentrations measured using this method, from 0 to 0.9 mg/mL, corresponds to the corresponding range in the blood. The possibility of changing the conductivity range of a glucose solution depending on the concentration of the GOx enzyme in the LB film will make it possible to develop glucose sensors for higher concentrations. Such technological sensors would be in demand in the food and pharmaceutical industries. The developed technology can become the basis for creating a new generation of acoustoelectronic biosensors in the case of using other enzymatic reactions.

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An antibody-detecting sensor is described that is based on a microwave electrodynamic resonator. A polystyrene film with immobilized bacteria deposited on a lithium niobate plate was placed at one end of the resonator and was used as the sensing element. The second end was electrically shorted. The frequency and depth of the reflection coefficient S11 for three resonances in the range 6.5-8.5 GHz were used as an analytical signal to examine antibody interactions with bacteria and determine the time required for cell immobilization. The sensor distinguished between situations in which bacteria interacted with specific antibodies and those in which no such interaction occurred (control). Although the cell-antibody interaction changed the frequency and depth of the second and third resonance peaks, the parameters of the first resonance peak did not change. The interaction of cells with nonspecific antibodies did not change the parameters of any of the peaks. These results are promising for use in the design of methods to detect specific antibodies, which can supplement the existing methods of antibody analysis.

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A comparative analysis of the responses of two types of acoustic waves (surface SAW and plate APW) with close frequencies and the same type of waves (SAW) with different frequencies toward various liquid vapors (water, acetone, ethanol) was carried out in this paper. Two types of films based on mycelium of higher fungus Ganoderma lucidum (Curtis) P. Karst (G. lucidum) prepared by various methods were used as sensitive coatings. These films were based on G. lucidum mycelium ethanolic (48% v/v) homogenizate (MEGl) and extract (EGl). A film deposition procedure compatible with acoustic devices technology was developed. Various piezoelectric substrates (YX-LiNbO3, 128 YX-LiNbO3) were used for appropriate acoustic delay lines production. It was found that additional SAW and APW attenuation associated with the appearance of mycelium films on the surface of the acoustic waveguide is two times greater for MEGL than for EGL films in the frequency range of 20-80 MHz The changes in acoustic wave amplitude and phase due to vapor absorption were measured and compared with each other, taking into account the differences in geometry of the samples. It was found that the phase response of the SAW delay lines with EGL films is three times higher than one with the presence of MEGL films for water and ethanol vapors. The films used are demonstrated good reproducibility and long-term stability for at least 2 months. Based on the results obtained, it was concluded that MEGl film is not appropriate for use in high frequency SAW delay lines as a sensitive coating. However, both types of the films (MEGl and EGl) could be used as sensitive coatings for low frequency SAW and APW sensors based on corresponding delay lines. Additionally, it was found that the films used are not sensitive to acetone vapor. As a result of the work carried out, a technique for creating sensitive films based on the mycelium of higher fungi compatible with the planar technology of acoustoelectronic delay lines was developed. The possibility of using such films for the development of gas SAW and APW sensors was shown.

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Co-crystallization of 180°-orienting σ-hole-accepting tectons, namely, 1,4-diisocyanobenzene (1) and 1,4-diisocyanotetramethylbenzene (2), with such homoditopic halogen bond donors as 1,4-diiodotetrafluorobenzene (1,4-FIB) and 4,4'-diiodoperfluorobiphenyl (4,4'-FIBP) afforded co-crystals 1 ⋅ 1,4-FIB, 1 ⋅ 4,4'-FIBP, and 2 ⋅ 1,4-FIB. Their solid-state structures exhibit 1D-supramolecular arrangements, which are based on poorly explored I⋅⋅⋅C halogen bonding; this study is the first in which the supramolecular assembly utilizing halogen bonding with a terminal C atom was performed. The use of the potentially tetrafunctional σ-hole accepting tetraiodoethylene (TIE) leads to supramolecular architecture of a higher dimension, 3D-framework, observed in the structure of 1 ⋅ TIE. DFT calculations, used to characterize the halogen bonding situation, revealed that the I⋅⋅⋅C non-covalent interactions are moderately strong, ranging from -4.07 in 1 ⋅ TIE to -5.45 kcal/mol in 2 ⋅ 1,4-FIB. The NBO analysis disclosed that LP(C)→σ* charge transfer effects are relevant in all co-crystals.

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The influence of the method of applying the activating additive ammonium chloride and its concentration on the density and microstructure of zinc oxide ceramic obtained by cold sintering at 244 °C was investigated. The activating agent was applied by two methods: impregnation and subsequent autoclave treatment. When the powder was activated by the impregnation method, the crystal sizes remained at the initial level of 0.17-0.19 µm. After the autoclave treatment, the crystal sizes increased to 0.31-0.53 µm. Samples of cold sintering ZnO with relative density up to 0.96 and average grain sizes 0.29-0.86 µm were obtained. ZnO powders and ceramic samples were analyzed using SEM, TGA/DSC, and XRD to reveal the effect of the powder activation method and cold sintering conditions on the material microstructure. The effect of ammonium chloride concentration on grain growth and microstructure of ceramic samples is shown. It was found that the average grain size of ceramic samples with an increase in additive concentration passes through a minimum. In cold sintering of the autoclave activated powder, the effect of reducing the average grain size was observed. The results of this work are discussed on the basis of the idea of the solid-phase mobility of the crystal structure arising when interacting with an aqueous medium.

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Backward acoustic waves are characterized by oppositely directed phase and group velocities. These waves can exist in isotropic and piezoelectric plates. They can be detected using a set of interdigital transducers with different spatial periods located on the same piezoelectric substrate. In this paper, the effect of a nonviscous and nonconductive liquid on the characteristics of a first-order backward antisymmetric wave in a YX plate of lithium niobate is studied theoretically and experimentally. It is shown that the presence of liquid does not lead to the transformation or disappearance of this wave. It is shown that these waves are close to the cutoff frequency and are characterized by the presence of a point with zero group velocity. The design of a liquid sensor based on these waves is proposed.

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Cyclometalated platinum(II) complexes [Pt(ppy)Cl(CNAr)] (ppy = 2-phenylpyridinato-C2,N; Ar = C6H4-2-I 1, C6H4-4-I 2, C6H3-2-F-4-I 3, and C6H3-2,4-I2 4) bearing ancillary isocyanide ligands were obtained by the bridge-splitting reaction between the dimer [Pt(ppy)(µ-Cl)]2 and 2 equiv any one of the corresponding CNAr. Complex 2 was crystallized in two polymorphic forms, namely, 2 I and 2 II, exhibiting green (emission quantum yield of 0.5%) and orange (emission quantum yield of 12%) phosphorescence, respectively. Structure-directing non-covalent contacts in these polymorphs were verified by a combination of experimental (X-ray diffraction) and theoretical methods (NCIplot analysis, combined electron localization function (ELF), and Bader quantum theory of atoms in molecules (QTAIM analysis)). A noticeable difference in the spectrum of non-covalent interactions of 2 I and 2 II is seen in the Pt···Pt interactions in 2 II and absence of these metallophilic contacts in 2 I. The other solid luminophores, namely, 1, 3 I-II, 4, and 4·CHCl3, exhibit green luminescence; their structures include intermolecular C-I···Cl-Pt halogen bonds as the structure-directing interactions. Crystals of 1, 2 I, 3 I, 3 II, 4, and 4·CHCl3 demonstrated a reversible mechanochromic color change achieved by mechanical grinding (green to orange) and solvent adsorption (orange to green).

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Using acoustic wave modes propagation in piezoelectric plates loaded with conductive liquids, peculiarities of the mode-liquid acoustoelectric interaction are studied. It is found that (i) in contrast to bulk and surface acoustic waves propagating in piezoelectric semiconductors, the acoustoelectric attenuation of the modes is not symmetric in respect to its maximum, (ii) a large increase in attenuation may be accompanied by a small decrease in phase velocity and vice versa, (iii) the peculiarities are valid for "pure" (without beam steering) and "not pure" (with beam steering) modes, as well as for modes of different orders and polarizations, and (iv) conductivity of test liquid increases electromagnetic leakage between input and output transducers, affecting results of the measurements. To decrease the leakage, the liquid should be localized between transducers, outside the zone over them. If so, the mode sensitivity may be as large as 8.6 dB/(S/m) for amplitude and 107°/(S/m) for phase. However, because of comparable cross-sensitivity towards viscosity and dielectric permittivity, modes with selective detection of liquid conductivity are not found.

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Some individuals with autism spectrum disorder (ASD) carry functional mutations rarely observed in the general population. We explored the genes disrupted by these variants from joint analysis of protein-truncating variants (PTVs), missense variants and copy number variants (CNVs) in a cohort of 63,237 individuals. We discovered 72 genes associated with ASD at false discovery rate (FDR) ≤ 0.001 (185 at FDR ≤ 0.05). De novo PTVs, damaging missense variants and CNVs represented 57.5%, 21.1% and 8.44% of association evidence, while CNVs conferred greatest relative risk. Meta-analysis with cohorts ascertained for developmental delay (DD) (n = 91,605) yielded 373 genes associated with ASD/DD at FDR ≤ 0.001 (664 at FDR ≤ 0.05), some of which differed in relative frequency of mutation between ASD and DD cohorts. The DD-associated genes were enriched in transcriptomes of progenitor and immature neuronal cells, whereas genes showing stronger evidence in ASD were more enriched in maturing neurons and overlapped with schizophrenia-associated genes, emphasizing that these neuropsychiatric disorders may share common pathways to risk.

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The additive manufacturing of BaTiO3 (BT) ceramics through stereolithography (SLA) 3D printing at 465 nm wavelength was demonstrated. After different milling times, different paste compositions with varied initial micron-sized powders were studied to find a composition suitable for 3D printing. The pastes were evaluated in terms of photopolymerization depth depending on the laser scanning speed. Furthermore, the microstructure and properties of the BT ceramic samples produced through SLA 3D printing were characterized and compared with those of ceramics fabricated through a conventional die semi-drying pressing method. Three-dimensional printed samples achieved relative densities over 0.95 and microhardness over 500 HV after sintering, nearly matching the relative density and microhardness attained by the pressed samples. Upon poling, the 3D-printed samples attained acceptable piezoelectric module d33 = 148 pC/N and dielectric constants over 2000. At near full density, BT piezoceramics were successfully fabricated through SLA 3D printing at 465 nm wavelength, achieving photopolymerization depth of more than 100 microns. This work paves the relatively low-cost way for 3D printing of piezoelectric ceramics using conventional micron-sized powders and high printed layer thickness.

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Properties of the Langmuir-Blodgett (LB) films of arachidic and stearic acids, versus the amount of the films' monolayers were studied and applied for chloroform vapor detection with acoustoelectric high-frequency SAW sensors, based on an AT quartz two-port Rayleigh type SAW resonator (414 MHz) and ST-X quartz SAW delay line (157.5 MHz). Using both devices, it was confirmed that the film with 17 monolayers of stearic acid deposited on the surface of the SAW delay line at a surface pressure of 30 mN/m in the solid phase has the best sensitivity towards chloroform vapors, compared with the same films with other numbers of monolayers. For the SAW resonator sensing using slightly longer arachidic acid molecules, the optimum performance was reached with 17 LB film layers due to a sharper decrease in the Q-factor with mass loading. To understand the background of the result, Atomic Force Microscopy (AFM) in intermittent contact mode was used to study the morphology of the films, depending on the number of monolayers. The presence of the advanced morphology of the film surface with a maximal average roughness (9.3 nm) and surface area (29.7 µm2) was found only for 17-monolayer film. The effects of the chloroform vapors on the amplitude and the phase of the acoustic signal for both SAW devices at 20 °C were measured and compared with those for toluene and ethanol vapors; the largest responses were detected for chloroform vapor. For the film with an optimal number of monolayers, the largest amplitude response was measured for the resonator-based device. Conversely, the largest change in the acoustic phase produced by chloroform adsorption was measured for delay-line configuration. Finally, it was established that the gas responses for both devices coated with the LB films are completely restored 60 s after chamber cleaning with dry air.

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RATIONALE: The In-In2 O3 system is regarded as a potential low-temperature source of gaseous indium oxide (In2 O) when obtaining functional materials by physical vapor deposition techniques. To date the vaporization thermodynamics of the system have been investigated in few studies, the results of which are contradictory. METHODS: The study of the In-In2 O3 system was performed using Knudsen effusion mass spectrometry in the temperature range 930-1210 K, with a magnet mass spectrometer (MS-1301). Quartz effusion cells heated by a resistance furnace were employed. RESULTS: It was established that In(g) and In2 O(g) are the major vapor species over heterogeneous mixtures (In(l) + In2 O3 (s)) and the gaseous oxide In2 O is predominant. The partial pressures of the vapor species were determined and the quantitative vapor composition was calculated. Based on the experimental data, a p-x section of the In-In2 O3 system phase diagram at 1060 K was constructed. The standard enthalpies of reactions accompanying vaporization of the In and In2 O3 mixtures were evaluated using the second- and third-law methods. The standard enthalpy of formation of In2 O(g) was derived from the enthalpies of reactions obtained. CONCLUSIONS: The predominance of In2 O in the equilibrium vapor over heterogeneous mixtures (In(l) + In2 O3 (s)), along with its high partial pressure at relatively low temperatures, substantiate the In-In2 O3 system to be suitable for physical vapor deposition methods. The obtained results can be used for physical vapor deposition parameter adjustment and optimization. The standard enthalpy of formation of In2 O(g) obtained in an independent way in the present work is in good agreement with that from our previous In2 O3 (s) vaporization study.