Search

This paper studies the general principal-agent framework in which the principal aims to implement his first-best action that is monotone in the unknown state. The principal privately selects a signal structure of the agent whose payoff depends on the principal's action, the state, and the privately known type. The agent privately observes the generated signal and reports it to the principal, who takes action. We show that by randomizing between two perfectly informative signal structures, the principal can elicit perfect information from the agent about the state and implement his first-best action regardless of the agent's type. As to the economic application, we consider the bilateral trade model with non-quasilinear preferences and private multi-dimensional information of the buyer, and show that the seller can extract full surplus by privately designing the buyer's signal structures. [ABSTRACT FROM AUTHOR]

To broaden the applications of yttria‐stabilized zirconia (YSZ) in mobile phone back panels and high‐end decorative materials, the 3 mol% YSZ (3YSZ) ceramics doped with erbium oxide (Er2O3) as colorant were successfully sintered at 1250 and 1350°C in air. The influences of Er2O3‐doping concentration and sintering temperature on the phase, microstructure, color, and mechanical properties of the pink Er2O3‐3YSZ ceramics were investigated. As the Er2O3 concentration increased, the redness value a* gradually increased, while the yellowness value b* and the lightness value L* gradually decreased. The highest value a* and b* of Er2O3‐3YSZ ceramics reached absolute values of 15.2 and 4.5, respectively. The effect of Er2O3 concentration is also depicted in detail, which also affects the mechanical properties including hardness and fracture toughness of the ceramics. The maximum hardness and fracture toughness of Er2O3‐3YSZ ceramics reached 13.9 ± 0.3 GPa and 6.21 ± 0.20 MPa·m1/2, respectively. The hardness of the ceramics exceeds 12.5 GPa, which is the required market index for further practical application. This work provides a method for preparing 3YSZ ceramics with excellent mechanical properties and bright pink color, which has the potential to be used in the fields of advanced and superior electronics in particular. [ABSTRACT FROM AUTHOR]

SUMMARY: Genome annotation files play a critical role in dictating the quality of downstream analyses by providing essential predictions for gene positions and structures. These files are pivotal in decoding the complex information encoded within DNA sequences. Here, we generated experimental data resolving RNA 5′‐ and 3′‐ends as well as full‐length RNAs for cassava TME12 sticklings in ambient temperature and cold. We used these data to generate genome annotation files using the TranscriptomeReconstructoR (TR) tool. A careful comparison to high‐quality genome annotations suggests that our new TR genome annotations identified additional genes, resolved the transcript boundaries more accurately and identified additional RNA isoforms. We enhanced existing cassava genome annotation files with the information from TR that maintained the different transcript models as RNA isoforms. The resultant merged annotation was subsequently utilized for comprehensive analysis. To examine the effects of genome annotation files on gene expression studies, we compared the detection of differentially expressed genes during cold using the same RNA‐seq data but alternative genome annotation files. We found that our merged genome annotation that included cold‐specific TR gene models identified about twice as many cold‐induced genes. These data indicate that environmentally induced genes may be missing in off‐the‐shelf genome annotation files. In conclusion, TR offers the opportunity to enhance crop genome annotations with implications for the discovery of differentially expressed candidate genes during plant–environment interactions. Significance Statement: Our work has broad implications for transcriptome analyses of plant–environment interactions: differentially expressed genes may be absent in commonly used annotations and would thus be missed. As solution, we suggest merging TR‐based annotations for specific conditions with existing genome annotation files. [ABSTRACT FROM AUTHOR]

In the paper, we construct a representation : FVB n → Aut (F 2 n) of the flat virtual braid group FVB n on n strands by automorphisms of the free group F 2 n with 2 n generators which does not preserve the forbidden relations in the flat virtual braid group. This representation gives a positive answer to the problem formulated by Bardakov in the list of unsolved problems in virtual knot theory and combinatorial knot theory by Fenn et al. Also we find the set of normal generators of the groups VP n ∩ H n in VB n , FVP n ∩ FH n in FVB n , GVP n ∩ GH n in GVB n , which play an important role in the study of the kernel of the representation  . [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is currently one of the most common tumor types diagnosed worldwide. In the early stages, the disease responds well to surgical and chemotherapeutic treatment, but in the later stages when therapeutic options are exhausted, comprehensive genomic profiling can guide further treatment decisions. We present the case of a 46-year-old man of Ashkenazi Jewish ancestry who was diagnosed with KRAS-mutated metastatic colorectal cancer. After surgery and progression on standard FOLFOX/FOLFIRI + bevacizumab therapy, as well as on Trifluridine/Tipiracil, comprehensive genomic profiling was performed with the hope of expanding therapeutic options. Following comprehensive tumor molecular profiling via NGS, a discussion of the case was discussed at the local molecular tumor board in order to determine further treatment strategy. An activating variant of KRAS and PIK3CA, FLT3 and SRC amplification and damaging TP53 and APC variants were discarded by MTB as potential targetable biomarkers. The BRCA2 p.S1415fs*4 founder frameshift variant was of interest and the patient was included in the clinical trial investigating the efficacy of a PARP inhibitor talazoparib. Unfortunately, the disease progression was detected within one month of talazoparib treatment and the patient died during the 8th cycle of FOLFIRI + bevacizumab therapy rechallenge. [ABSTRACT FROM AUTHOR]

In this work, the possibility of fabricating composite magneto-optical ceramics by electrophoretic deposition (EPD) of nanopowders and high-temperature vacuum sintering of the compacts was investigated. Holmium oxide was chosen as a magneto-optical material for the study because of its transparency in the mid-IR range. Nanopowders of magneto-optical (Ho0.95La0.05)2O3 (HoLa) material were made by self-propagating high-temperature synthesis. Nanopowders of (Y0.9La0.1)2O3 (YLa) were made by laser synthesis for an inactive matrix. The process of formation of one- and two-layer compacts by EPD of the nanopowders from alcohol suspensions was studied in detail. Acetylacetone was shown to be a good dispersant to obtain alcohol suspensions of the nanopowders, characterized by high zeta potential values (+29–+80 mV), and to carry out a stable EPD process. One-layer compacts were made from the HoLa and YLa nanopowders with a density of 30–43%. It was found out that the introduction of polyvinyl butyral (PVB) into the suspension leads to a decrease in the mass and thickness of the green bodies deposited, but does not significantly affect their density. The possibility of making two-layer (YLa/HoLa) compacts with a thickness of up to 2.6 mm and a density of up to 46% was demonstrated. Sintering such compacts in a vacuum at a temperature of 1750 °C for 10 h leads to the formation of ceramics with a homogeneous boundary between the YLa/HoLa layers and a thickness of the interdiffused ion layer of about 30 μm. [ABSTRACT FROM AUTHOR]

We successfully synthesized millimeter-sized single crystals of the molecular erbium(III) complex Er(acac)3(cphen), where acac = acetylacetonate and cphen = 5-chloro-1,10-phenanthroline. The novelty of this work stems from the exhaustive examination of the polar and electronic properties of the obtained samples at the macro-, micro-, and nanoscale levels. The single crystal X-ray diffraction method demonstrates the monoclinic (noncentrosymmetric space group P21) crystallographic structure of the synthesized samples and scanning electron microscopy exhibits the terrace–ledge morphology of the surface in erbium(III) crystals. By using the piezoelectric force microscopy mode, the origin of the polar properties and the hyperpolarizability in the synthesized samples were assigned to the internal domain structure framed by the characteristic terrace–ledge topography. The direct piezoelectric coefficient (~d33) was found to be intensely dependent on the local area and was measured in the range of 4–8 pm/V. A nanoscale study using the kelvin probe force and capacitance force (dC/dz) microscopy modes exposed the effect of the Er ions clustering in the erbium(III) complex. The PFM method applied solely to the Er ion revealed the corresponding direct piezoelectric coefficient (~d33) of about 4 pm/V. Given the maximum piezoelectric coefficient in the erbium(III) complex at 8 pm/V, we highlight the significant importance of the spatial coordination between the lanthanide ion and the ligands. The polar coordination between the lanthanide ion and the nitrogen and oxygen atoms was also corroborated by Raman spectroscopy supported by the density functional theory calculations. The obtained results can be of paramount importance for the application of molecular erbium(III) complex crystals in low-magnitude magnetic or electric field devices, which would reduce the energy consumption and speed up the processing switching in nonvolatile memory devices. [ABSTRACT FROM AUTHOR]

The piezoelectric market is ruled by lead-based compounds that should be substituted by environmentally friendly materials. Despite the substantial literature on lead-free candidates available, stress effects on the dielectric, piezoelectric and ferroelectric performance of thin films from the nano- to macroscale have been barely addressed until now. In this work, a combination of multiscale characterization techniques is used to disclose the induced mechanical deformation impact on the dielectric, polar and structural properties of polycrystalline lead-free potassium sodium niobate (KNN) thin films fabricated on platinized silicon (Pt/Si(100)), strontium titanate (Pt/STO(100)) and magnesium oxide (Pt/MgO(100)) substrates. A tensile residual stress state characterizes KNN films on Pt/Si (+210 ± 28 MPa), while KNN films on Pt/STO and Pt/MgO (−411 ± 18 MPa and −494 ± 26 MPa, respectively) evidence a compressive residual stress condition. Films with the highest compressive state (on Pt/MgO) exhibit the lowest dielectric losses with the highest electric permittivity and the maximum electric polarization; concomitantly they present the most dense and homogeneous microstructure, with small grains and a narrow grain size distribution. In contrast, tensile residual stress films (on Pt/Si) show the smallest polarization with an almost negligible out-of-plane component of piezoresponse. Of relevance, phase transition temperatures are markedly affected by the type and magnitude of the residual stress: they are the lowest for KNN films on Pt/MgO and highest for KNN films on Pt/Si. The narrowest temperature range for tetragonal phase is recorded for KNN films on Pt/MgO. For the first time, an approach to generate a morphotropic phase boundary in KNN thin films by use of compressive residual stress is thus demonstrated. This work highlights the impact of stress, as a key parameter in the performance of KNN polycrystalline thin films. These results have implications in terms of understanding lead-free ferroelectric/piezoelectric behaviour and its application/commercialization. [ABSTRACT FROM AUTHOR]

This review discusses current standards, limitations, pitfalls, and future perspectives of MSI detection. [ABSTRACT FROM AUTHOR]

How the noncoding genome affects cellular functions is a key biological question. A particular challenge is to distinguish the effects of noncoding DNA elements from long noncoding RNAs (lncRNAs) that coincide at the same loci. Here, we identified the flowering‐associated intergenic lncRNA (FLAIL) in Arabidopsis through early flowering flail mutants. Expression of FLAIL RNA from a different chromosomal location in combination with strand‐specific RNA knockdown characterized FLAIL as a trans‐acting RNA molecule. FLAIL directly binds to differentially expressed target genes that control flowering via RNA–DNA interactions through conserved sequence motifs. FLAIL interacts with protein and RNA components of the spliceosome to affect target mRNA expression through co‐transcriptional alternative splicing (AS) and linked chromatin regulation. In the absence of FLAIL, splicing defects at the direct FLAIL target flowering gene LACCASE 8 (LAC8) correlated with reduced mRNA expression. Double mutant analyses support a model where FLAIL‐mediated splicing of LAC8 promotes its mRNA expression and represses flowering. Our study suggests lncRNAs as accessory components of the spliceosome that regulate AS and gene expression to impact organismal development. Synopsis: An early flowering mutant screen was used to identify flail, a mutant mapping to a non‐coding region of the genome. This study shows that the locus encodes for the long noncoding RNA FLAIL, which serves as an accessory component of the spliceosome that regulates alternative splicing and gene expression to repress flowering. FLAIL is a trans‐acting RNA molecule that represses flowering.FLAIL binds to chromatin regions of target genes through conserved sequence motifs.FLAIL interacts with the spliceosome complex to affect target mRNA expression by co‐transcriptional alternative splicing process and regulation of chromatin modifications.FLAIL represses flowering by regulating alternative splicing and inducing mRNA expression of its direct flowering target LAC8. [ABSTRACT FROM AUTHOR]

Simple Summary: Microsatellite instability (MSI) occurs in a wide variety of tumor types and is one of the most important predictive biomarkers for immune checkpoint inhibitor therapy. The present review aims to summarize the molecular characteristics of MSI tumors as well as the results of major clinical studies evaluating the efficacy of checkpoint inhibitors in the treatment of patients with MSI tumors. Microsatellite instability (MSI) is one of the most important molecular characteristics of a tumor, which occurs among various tumor types. In this review article, we examine the molecular characteristics of MSI tumors, both sporadic and Lynch-associated. We also overview the risks of developing hereditary forms of cancer and potential mechanisms of tumor development in patients with Lynch syndrome. Additionally, we summarize the results of major clinical studies on the efficacy of immune checkpoint inhibitors for MSI tumors and discuss the predictive role of MSI in the context of chemotherapy and checkpoint inhibitors. Finally, we briefly discuss some of the underlying mechanisms causing therapy resistance in patients treated with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Natural and artificial radioactivity of bottom sediment in the six lakes of the Western and Central Caucasus have been evaluated. It allowed to define the variation of sedimentation rate during the last 100–150 years using technogenic (137Cs) and natural (210Pb, 226Ra) radionuclides as a chronomarkers. The studied lakes are located in the contrasting geographic conditions, different orographic positions, and have different origin. The average annual precipitation in the area of each of the lakes has been detected to stay relatively constant during the 137Cs fallout period, while the air temperature has markedly increased during the last decades. The detected sedimentation rates are the indirect indicator of climate change in the mountains. They are slightly decreasing owing to the increased protection of soil by vegetation cover in the lower altitude zone; in the upper zones, they are growing due to accelerated glacier retreat. The radioecological situation is estimated as normal. High levels of 137Cs (33 kBq m−2) and 241Am (0.1 kBq m−2) in bottom sediments are attributed to the region-specific geographical characteristics. [ABSTRACT FROM AUTHOR]

Natural polymers such as cellulose have interesting tribo- and piezoelectric properties for paper-based energy harvesters, but their low performance in providing sufficient output power is still an impediment to a wider deployment for IoT and other low-power applications. In this study, different types of celluloses were combined with nanosized carbon fillers to investigate their effect on the enhancement of the electrical properties in the final nanogenerator devices. Cellulose pulp (CP), microcrystalline cellulose (MCC) and cellulose nanofibers (CNFs) were blended with carbon black (CB), carbon nanotubes (CNTs) and graphene nanoplatelets (GNPs). The microstructure of the nanocomposite films was characterized by scanning electron and probe microscopies, and the electrical properties were measured macroscopically and at the local scale by piezoresponse force microscopy. The highest generated output voltage in triboelectric mode was obtained from MCC films with CNTs and CB, while the highest piezoelectric voltage was produced in CNF-CNT films. The obtained electrical responses were discussed in relation to the material properties. Analysis of the microscopic response shows that pulp has a higher local piezoelectric d33 coefficient (145 pC/N) than CNF (14 pC/N), while the macroscopic response is greatly influenced by the excitation mode and the effective orientation of the crystals relative to the mechanical stress. The increased electricity produced from cellulose nanocomposites may lead to more efficient and biodegradable nanogenerators. [ABSTRACT FROM AUTHOR]

Studies of exciton and hole stabilization in multichromophoric systems underpin our understanding of electron transfer and transport in materials and biomolecules. The simplest model systems are dimeric, and recently we compared the gas-phase spectroscopy and dynamics of van der Waals dimers of fluorene, 9-methylfluorene (MF), and 9,9′-dimethylfluorene (F1) to assess how sterically controlled facial encumbrance modulates the dynamics of excimer formation and charge resonance stabilization (CRS). Dimers of fluorene and MF show only excimer emission upon electronic excitation, and significant CRS as evidenced in a reduced ionization potential for the dimer relative the monomer. By contrast, the dimer of F1 shows no excimeric emission, rather structured emission from the locally excited state of a tilted (non π-stacked) dimer, evidencing the importance of C–H/π interactions and increased steric constraints that restrict a cofacial approach. In this work, we report our full results on van der Waals clusters of F1, using a combination of theory and experiments that include laser-induced fluorescence, mass-selected two-color resonant two-photon ionization spectroscopy, and two-color appearance potential measurements. We use the latter to derive the binding energies of the F1 dimer in ground, excited, and cation radical states. Our results are compared with van der Waals and covalently linked clusters of fluorene to assess both the relative strength of π-stacking and C–H/π interactions in polyaromatic assemblies and the role of π-stacking in excimer formation and CRS. [ABSTRACT FROM AUTHOR]

In the present work, a study was carried out to investigate the key factors that determine the uniformity, mass, thickness, and density of compacts obtained from nanopowders of solid solutions of yttrium and lanthanum oxides ((LaxY1−x)2O3) with the help of the electrophoretic deposition (EPD). Nanopowders were obtained by laser ablation of a mixture of powders of yttrium oxide and lanthanum oxide in air. The implemented mechanisms of the EPD and factors of stability of alcohol suspensions are analyzed. It has been shown that acetylacetone with a concentration of 1 mg/m2 can be used as a dispersant for stabilization of isopropanol suspensions of the nanoparticles during the EPD. It was shown that the maximum density of dry compacts with a thickness of 2.4 mm reaches 37% of theoretical when EPD is performed in vertical direction from a suspension of nanopowders with addition of acetylacetone. [ABSTRACT FROM AUTHOR]

Organic polar crystalline materials, featuring the merits of lightweight, flexibility, and low fabrication costs, are emerging as promising alternatives for inorganic ferroelectrics, but so far, they are not competitive. The main reasons are the moderate polar properties of such materials and the fact that the temperature of the phase transition from polar to nonpolar states (Curie point) is typically located near room temperature. The organic molecular crystal of the fluorenone derivative 2,7‐diphenyl‐9H‐fluorene‐9‐one (DPFO) is demonstrated to feature robust high‐temperature piezo‐ and ferro‐electric properties, with a relatively high local piezoelectric coefficient (d33) of ≈120 pm V−1. The origin of the strong piezoelectricity is attributed to the presence of intrinsic domain structures in the DPFO microfiber crystals, originating from intramolecular co‐operation between the central fluorenone backbone and the external phenyl rings that are found stable up to 423 K. Moreover, this intramolecular co‐operation and the corresponding polar properties are found to depend on the thickness of the DPFO microfiber, resulting in a change from ferroelectric (<0.5 µm) to piezoelectric (≥0.5 µm) behavior. Considering the low cost and flexible production of such fluorenone‐based organic lead‐free ferroelectrics, this is a very promising strategy toward technological applications in electromechanical actuators, sensors, energy harvesters, and non‐volatile memory cells. [ABSTRACT FROM AUTHOR]

The article presents the results of research aimed at collecting and systematizing information about the settlements of the Volga Bulgaria period (10th - early 13th centuries). For the first time in Russia, field studies of 88 medieval settlements of different size were carried out using UAVs and GNSS equipment. The collected information was compiled into a geoinformation database with 36 qualitative and quantitative parameters for 95 objects (medieval settlements). Based on the obtained data, for the first time for the study area, "Country of Cities" web resource was created, which allows access to analytical and generalizing information about each studied fortified settlement of the Volga Bulgaria period. The combination of the descriptive component and the cartographic module makes it possible to assess not only the regularities of the hillfort's placement in the studied territory, but also to study individual archaeological objects in detail by interactive textured three-dimensional models. The analysis made it possible to specify the location and boundaries of the fortified settlements, to assess the current state and the risks of destruction under the influence of natural and anthropogenic factors. [ABSTRACT FROM AUTHOR]

This paper studies the possibility of using the WaTEM/SEDEM model to assess sediment yield from the catchment area within the Lena River catchment. The study was carried out based on a comparison of predicted data and measured data of the suspended sediment yield at the gauging stations of the state monitoring network of Russia. The study was performed within two areas, with plain and mountainous relief. The first site is located within the catchment area of the river Chara with an area of 4150 km2. The second site rests on the catchment area of the Lena River between the Tabaginskiy and Kangalassky capes near Yakutsk city. The catchment area of this site is 15,740 km2. The values of sediment yield from the "Yakutsk" catchment area are in much better agreement with the values of the measured sediment yield values than in the "Chara" catchment area. The predicted sediment yield from the study area remained almost unchanged from the period 1986–2019 and amounted to 3.5 t/km2, while the suspended sediment yield in the Lena at the Tabaga gauging station slightly increased from 7 to 9.45 t/km2 per year. [ABSTRACT FROM AUTHOR]

The SEA/Balance (soil erosion–accumulation balance) model and the WATEM/SEDEM model both mapping the erosion–accumulation budget of sediment within river basins were tested for 11 river basins of the eastern Russian Plain. The dynamics of river sediment yield were evaluated within one of the river basins. The analysis is based on observations of suspended sediment yield in test river basins with an area ranging from 100 to 1500 km2. The maps of the average annual erosion–accumulative budget of sediment were constructed using two methods, making it possible to quantitatively assess the amount of sediment yield from the catchment area for the river basins under study. The WATEM/SEDEM model and the author's SEA/Balance model were used for sediment yield estimation. The results of calculation using the WATEM/SEDEM model have an average bias of +11% compared to observed suspended sediment yield. The corresponding value in the case of the SEA/Balance model application is −29%. SEA/Balance model assessment sediment yield dynamics for the Sterlya river basin show an 11 percent reduction. It is possible to conclude that the proposed method of SEA/Balance can be applied to river basins of the agricultural zone of the east Russian Plain. [ABSTRACT FROM AUTHOR]

PARP inhibitors have recently emerged as a maintenance treatment option for metastatic pancreatic cancer patients with germline BRCA mutations. However, the possibility of PARP-inhibitor use as a standalone-targeted therapy for patients with various homologous repair pathway alterations remains mostly undetermined. Here we report a clinical case of a 56-yearold woman with pancreatic ductal adenocarcinoma harboring a somatic PALB2 mutation. Following disease progression after 10 cycles of FOLFIRINOX chemotherapy and two cycles of second-line gemcitabine, she was switched to talazoparib and achieved a complete clinical response after 25 months of treatment. The patient remains alive without clinical or radiological signs of disease progression three years after the start of talazoparib with no targeted therapy-related toxicities. This case highlights the role of broad molecular profiling as a window of opportunity to achieve a durable response for selected pancreatic cancer patients while pinpointing our gaps in understanding the whole picture of management of these patients since a new puzzle element represented by PARP inhibitors was introduced to clinical practice. [ABSTRACT FROM AUTHOR]

In the present paper, we study structural aspects of certain quotients of braid groups and virtual braid groups. In particular, we construct and study linear representations B n → GL n ⁢ (n - 1) / 2 ⁢ (Z ⁢ [ t ± 1 ]) , VB n → GL n ⁢ (n - 1) / 2 ⁢ (Z ⁢ [ t ± 1 , t 1 ± 1 , t 2 ± 1 , ... , t n - 1 ± 1 ]) which are connected with the famous Lawrence–Bigelow–Krammer representation. It turns out that these representations induce faithful representations of the crystallographic groups B n / P n ′ , VB n / VP n ′ , respectively. Using these representations we study certain properties of the groups B n / P n ′ , VB n / VP n ′ . Moreover, we construct new representations and decompositions of the universal braid groups UB n . [ABSTRACT FROM AUTHOR]

Background: A fraction of patients referred for complex molecular profiling of biopsied tumors may harbor germline variants in genes associated with the development of hereditary cancer syndromes (HCS). Neither the bioinformatic analysis nor the reporting of such incidental germline findings are standardized.Methods: Data from Next-Generation Sequencing (NGS) of biopsied tumor samples referred for complex molecular profiling were analyzed for germline variants in HCS-associated genes. Analysis of variant origin was performed employing bioinformatic algorithms followed by manual curation. When possible, the origin of the variant was validated by Sanger sequencing of the sample of normal tissue. The variants' pathogenicity was assessed according to ACMG/AMP.Results: Tumors were sampled from 183 patients (Males: 75 [41.0%]; Females: 108 [59.0%]; mean [SD] age, 57.7 [13.3] years) and analysed by targeted NGS. The most common tumor types were colorectal (19%), pancreatic (13%), and lung cancer (10%). A total of 56 sequence variants in genes associated with HCS were detected in 40 patients. Of them, 17 variants found in 14 patients were predicted to be of germline origin, with 6 variants interpreted as pathogenic (PV) or likely pathogenic (LPV), and 9 as variants of uncertain significance (VUS). For the 41 out of 42 (97%) missense variants in HCS-associated genes, the results of computational prediction of variant origin were concordant with that of experimental examination. We estimate that Sanger sequencing of a sample of normal tissue would be required for ~ 1-7% of the total assessed cases with PV or LPV, when necessity to follow with genetic counselling referral in ~ 2-15% of total assessed cases (PV, LPV or VUS found in HCS genes).Conclusion: Incidental findings of pathogenic germline variants are common in data from cancer patients referred for complex molecular profiling. We propose an algorithm for the management of patients with newly detected variants in genes associated with HCS. [ABSTRACT FROM AUTHOR]

Nucleosome‐depleted regions (NDRs) at gene promoters support initiation of RNA polymerase II transcription. Interestingly, transcription often initiates in both directions, resulting in an mRNA and a divergent non‐coding (DNC) transcript of unclear purpose. Here, we characterized the genetic architecture and molecular mechanism of DNC transcription in budding yeast. Using high‐throughput reverse genetic screens based on quantitative single‐cell fluorescence measurements, we identified the Hda1 histone deacetylase complex (Hda1C) as a repressor of DNC transcription. Nascent transcription profiling showed a genome‐wide role of Hda1C in repression of DNC transcription. Live‐cell imaging of transcription revealed that mutations in the Hda3 subunit increased the frequency of DNC transcription. Hda1C contributed to decreased acetylation of histone H3 in DNC transcription regions, supporting DNC transcription repression by histone deacetylation. Our data support the interpretation that DNC transcription results as a consequence of the NDR‐based architecture of eukaryotic promoters, but that it is governed by locus‐specific repression to maintain genome fidelity. Synopsis: The biological significance and global factors regulating eukaryotic divergent non‐coding (DNC) transcript initiation from shared nucleosome depleted regions remains elusive. Yeast reverse‐genetic screening identifies a novel factor repressing DNC transcription. The Hda1 histone deacetylase complex (Hda1C) functions as a repressor of DNC transcription.Hda1C represses nascent DNC transcripts and alters histone acetylation levels genome‐wide.Mutation of Hda1C subunit Hda3 increases transcription frequency of a DNC transcript in real‐time.Identification of specific repressors indicates that DNC transcription is rooted in eukaryotic promoter architecture. [ABSTRACT FROM AUTHOR]

This paper develops a new approach—based on the majorization theory—to the information design problem in Bayesian persuasion mechanisms, i.e., models in which the sender selects the signal structure of the agent(s) who then reports it to the non-strategic receiver. We consider a class of mechanisms in which the posterior payoff of the sender depends on the value of a realized posterior mean of the state, its order in the sequence of possible means, and the marginal distribution of signals. We provide a simple characterization of mechanisms in which optimal signal structures are monotone partitional. Our approach has two economic implications: it is invariant to monotone transformations of the state and allows to decompose setups with multiple agents into independent Bayesian persuasion mechanisms with a single agent. As the main application of our characterization, we show the optimality of monotone partitional signal structures in all selling mechanisms with independent private values and quasi-linear preferences. We also provide sharp characterization of optimal signal structures for second-price auctions and posted-price sales. [ABSTRACT FROM AUTHOR]

atomistic biomolecular simulations--is usually parameterized by least-squares (LS) fitting of the point charge values to a reference electrostatic potential, a procedure that suffers from numerical instabilities due to the ill-conditioned nature of the LS problem. To reveal the origins of this ill-conditioning, we start with a general treatment of the point charge fitting problem as an inverse problem and construct an analytical model with the point charges spherically arranged according to Lebedev quadrature which is naturally suited for the inverse electrostatic problem. This analytical model is contrasted to the atom-centered point-charge model that can be viewed as an irregular quadrature poorly suited for the problem. This analysis shows that the numerical problems of the point charge fitting are due to the decay of the curvatures corresponding to the eigenvectors of LS sum Hessian matrix. In part, this ill-conditioning is intrinsic to the problem and is related to decreasing electrostatic contribution of the higher multipole moments, that are, in the case of Lebedev grid model, directly associated with the Hessian eigenvectors. For the atom-centered model, this association breaks down beyond the first few eigenvectors related to the high-curvature monopole and dipole terms; this leads to even wider spread-out of the Hessian curvature values. Using these insights, it is possible to alleviate the ill-conditioning of the LS point-charge fitting without introducing external restraints and/or constraints. Also, as the analytical Lebedev grid PC model proposed here can reproduce multipole moments up to a given rank, it may provide a promising alternative to including explicit multipole terms in a force field. [ABSTRACT FROM AUTHOR]

Atom-centered point charge (PC) model of the molecular electrostatics--a major workhorse of the atomistic biomolecular simulations--is usually parameterized by least-squares (LS) fitting of the point charge values to a reference electrostatic potential, a procedure that suffers from numerical instabilities due to the ill-conditioned nature of the LS problem. To reveal the origins of this ill-conditioning, we start with a general treatment of the point charge fitting problem as an inverse problem and construct an analytical model with the point charges spherically arranged according to Lebedev quadrature which is naturally suited for the inverse electrostatic problem. This analytical model is contrasted to the atom-centered point-charge model that can be viewed as an irregular quadrature poorly suited for the problem. This analysis shows that the numerical problems of the point charge fitting are due to the decay of the curvatures corresponding to the eigenvectors of LS sum Hessian matrix. In part, this ill-conditioning is intrinsic to the problem and is related to decreasing electrostatic contribution of the higher multipole moments, that are, in the case of Lebedev grid model, directly associated with the Hessian eigenvectors. For the atom-centered model, this association breaks down beyond the first few eigenvectors related to the high-curvature monopole and dipole terms; this leads to even wider spread-out of the Hessian curvature values. Using these insights, it is possible to alleviate the ill-conditioning of the LS point-charge fitting without introducing external restraints and/or constraints. Also, as the analytical Lebedev grid PC model proposed here can reproduce multipole moments up to a given rank, it may provide a promising alternative to including explicit multipole terms in a force field. [ABSTRACT FROM AUTHOR]

Transport properties of Li+ mobile ions in fresh and aged LiMn2O4 battery cathodes were studied at the nanoscale via electrochemical strain microscopy (ESM), time spectroscopy, and voltage spectroscopy mapping. Both Vegard and plausible non-Vegard contributions to the ESM signal were identified in electrochemical hysteresis loops obtained on fresh and aged samples. In the fresh cathodes, the Vegard contribution dominates the signal, while in the aged samples different shape of hysteresis loops indicates an additional plausible non-Vegard contribution. Non-uniform spatial distribution of the electrochemical loop opening in LiMn2O4 particles studied in the aged samples indicates stronger variation of the Li diffusion coefficient at the microscale as compared to the fresh specimens. Time spectroscopy measurements revealed a suppression of the local Li diffusivity in aged samples. The mechanisms of the cathode aging are discussed in the context of observed nanoscale ESM response. [ABSTRACT FROM AUTHOR]

Escitalopram is one of the most commonly used antidepressant drugs but exhibits a substantial interindividual variation in clinical response. A key factor underlying response differences is the polymorphic nature of the CYP2C19 gene encoding the major enzyme responsible for escitalopram metabolism. Although pre‐emptive CYP2C19 genotyping may improve escitalopram treatment outcome by dose individualization, much of the interindividual variability cannot be assigned to the currently known CYP2C19 gene variants. The aim of the present study was to search for novel CYP2C‐haplotypes for better genetic prediction of escitalopram metabolism. First, the CYP2C18/CYP2C19 locus was sequenced from gDNA obtained from 24 patients previously genotyped as CYP2C19*1/*1 showing consistently low serum concentrations of escitalopram (< 25 nM/10 mg). Three new haplotypes of the CYP2C locus (CYP2C:TG, CYP2C:TA, and CYP2C:CG) were here identified, and their functional roles were evaluated using gDNA from 875 previously genotyped escitalopram‐treated patients. The CYP2C:CG and CYP2C:TA haplotypes had no significant impact on escitalopram concentration. Based on the estimated effects of the novel CYP2C‐haplotypes on escitalopram exposure, the predicted serum concentrations of escitalopram in homozygous CYP2C:TG and CYP2C19*17 carriers were 24.8% and 17.3% lower compared with the baseline (CYP2C:CG and CYP2C:TA), respectively. In conclusion, a novel CYP2C‐haplotype defined by rs2860840T and rs11188059G associated with ultrarapid metabolism of escitalopram was identified. Further studies should clarify the genetic basis for the enhanced escitalopram metabolism and the impact of the CYP2C:TG haplotype on the metabolism of other CYP2C19 substrates like omeprazole, voriconazole, and clopidogrel. [ABSTRACT FROM AUTHOR]

An alternative approach is proposed to improve the conventional (based on the low‐temperature grown GaAs and Si‐doped GaAs superlattice) photoconductive antenna (PCA) performance by modification of the planar electrodes design and crystallographic orientations of the GaAs substrate ((100) and (111)‐A). The electrode scheme design includes a combination of logarithmic spiral, bow‐tie, and plasmonic antennas and results in appearance of sharp resonant peaks, high spectral bandwidth and high signal‐to‐noise ratio, and significant enhancement of the output terahertz (THz) power. The material design leads to significant increase in the THz output power (by 6.4 in GaAs (100), by 5.6 in GaAs (111)‐A PCAs) regarding to a conventional antenna. The substrate crystallographic cut direction influences the relaxation time constant of photoexcited charge carriers being an order of magnitude smaller in the sample grown on the GaAs (111)‐A than in the one on the GaAs (100). The simulation model supports experimental results demonstrating that the optimal period of the plasmonic antenna grid providing the highest efficiency of THz radiation generation, is about 200 nm. Comparison of the THz spectra in manufactured antennas against the conventional stripline PCA shows a broadening band toward the low‐frequency region down to 0.1 THz with a resonance at 0.2 THz. [ABSTRACT FROM AUTHOR]

Background: The quality of gene annotation determines the interpretation of results obtained in transcriptomic studies. The growing number of genome sequence information calls for experimental and computational pipelines for de novo transcriptome annotation. Ideally, gene and transcript models should be called from a limited set of key experimental data. Results: We developed TranscriptomeReconstructoR, an R package which implements a pipeline for automated transcriptome annotation. It relies on integrating features from independent and complementary datasets: (i) full-length RNA-seq for detection of splicing patterns and (ii) high-throughput 5′ and 3′ tag sequencing data for accurate definition of gene borders. The pipeline can also take a nascent RNA-seq dataset to supplement the called gene model with transient transcripts. We reconstructed de novo the transcriptional landscape of wild type Arabidopsis thaliana seedlings and Saccharomyces cerevisiae cells as a proof-of-principle. A comparison to the existing transcriptome annotations revealed that our gene model is more accurate and comprehensive than the most commonly used community gene models, TAIR10 and Araport11 for A.thaliana and SacCer3 for S.cerevisiae. In particular, we identify multiple transient transcripts missing from the existing annotations. Our new annotations promise to improve the quality of A.thaliana and S.cerevisiae genome research. Conclusions: Our proof-of-concept data suggest a cost-efficient strategy for rapid and accurate annotation of complex eukaryotic transcriptomes. We combine the choice of library preparation methods and sequencing platforms with the dedicated computational pipeline implemented in the TranscriptomeReconstructoR package. The pipeline only requires prior knowledge on the reference genomic DNA sequence, but not the transcriptome. The package seamlessly integrates with Bioconductor packages for downstream analysis. [ABSTRACT FROM AUTHOR]

Background: The quality of gene annotation determines the interpretation of results obtained in transcriptomic studies. The growing number of genome sequence information calls for experimental and computational pipelines for de novo transcriptome annotation. Ideally, gene and transcript models should be called from a limited set of key experimental data. Results: We developed TranscriptomeReconstructoR, an R package which implements a pipeline for automated transcriptome annotation. It relies on integrating features from independent and complementary datasets: (i) full-length RNA-seq for detection of splicing patterns and (ii) high-throughput 5′ and 3′ tag sequencing data for accurate definition of gene borders. The pipeline can also take a nascent RNA-seq dataset to supplement the called gene model with transient transcripts. We reconstructed de novo the transcriptional landscape of wild type Arabidopsis thaliana seedlings and Saccharomyces cerevisiae cells as a proof-of-principle. A comparison to the existing transcriptome annotations revealed that our gene model is more accurate and comprehensive than the most commonly used community gene models, TAIR10 and Araport11 for A.thaliana and SacCer3 for S.cerevisiae. In particular, we identify multiple transient transcripts missing from the existing annotations. Our new annotations promise to improve the quality of A.thaliana and S.cerevisiae genome research. Conclusions: Our proof-of-concept data suggest a cost-efficient strategy for rapid and accurate annotation of complex eukaryotic transcriptomes. We combine the choice of library preparation methods and sequencing platforms with the dedicated computational pipeline implemented in the TranscriptomeReconstructoR package. The pipeline only requires prior knowledge on the reference genomic DNA sequence, but not the transcriptome. The package seamlessly integrates with Bioconductor packages for downstream analysis. [ABSTRACT FROM AUTHOR]

This paper presents new multi-proxy records of the Holocene environmental and climatic changes in the Western Caucasus revealed from a continuous sediment sequence from mountainous Lake Khuko (Caucasus State Natural Biospheric Reserve, 1744 m a.s.l.). Palaeoecological analyses of a sediment core for grain size, magnetic susceptibility, loss on ignition, and pollen allowed us to determine five principal climatic phases with several subphases since 10.5 ka BP. The age model is based on seven accelerator mass spectrometry 14C dates, supplemented by 210Pb data for the uppermost part of the sediment core. Warm periods (10.5–6.7, 6.7–5.5, 3.5–2.4, 0.8–0.5 ka BP) were characterized by high biological productivity in the lake as indicated by high organic matter content and expansion of forests, typical of modern low and middle mountain zones, as indicated by the increase in abundance of Quercus, Ulmus, Corylus, and Tilia in the pollen assemblages. Cold periods (5.5–3.5, 2.4–0.8, and 0.5 ka BP–present) are marked by a consistent decrease in organic matter content in lake deposits and possibly higher intensity of the catchment erosion. The changes in pollen assemblages (for instance peaks of Abies, Picea, and Pinus) suggested a potential elevational decline in the boundaries of vegetation belts and expansion of high-altitude woodlands. Abrupt changes in the lake ecosystem were identified between 4.2 and 3.5 ka cal BP marked by a short-term variation in sediment regime shown by variation in organic matter content, magnetic susceptibility values, and sediment grain size. This was probably caused by climatic fluctuations in the Western Caucasus region as a result of complex shifts in the ocean-atmosphere system during the 4.2 ka event. Overall, the first Holocene multi-proxy continuous lake sediment record provides new insights into the climate history in the Western Caucasus. [ABSTRACT FROM AUTHOR]

The paper discusses the numerical algorithm constructing a three-dimensional model for a flow of two-phase incompressible fluid caused by the mass force of gravity in a porous medium. The algorithm is based on a combination of a hybrid upwind method with an explicit scheme for determination of the saturation. The hybrid upwinding allows us to take into account flows of fluid of various nature (in this case, viscous and gravitational flows) separately, which is extremely important in the case of gravitational flow with opposite directions of phase flows. The explicit scheme being extremely simple in implementation provides a small dispersion of solutions on discontinuities. The proposed algorithm is illustrated by the results of numerical experiments demonstrating the monotonicity of the method considered in this paper. [ABSTRACT FROM AUTHOR]

Optical cycling, a continuous photon scattering off atoms or molecules, plays a central role in the quantum information science. While optical cycling has been experimentally achieved for many neutral species, few molecular ions have been investigated. We present a systematic theoretical search for diatomic molecular ions suitable for optical cycling using equation-of-motion coupled-cluster methods. Inspired by the electronic structure patterns of laser-cooled neutral molecules, we establish the design principles for molecular ions and explore various possible cationic molecular frameworks. The results show that finding a perfect molecular ion for optical cycling is challenging, yet possible. Among various possible diatomic molecules we suggest several candidates, which require further attention from both theory and experiment: YF+, SiO+, PN+, SiBr+, and BO+. [ABSTRACT FROM AUTHOR]

Transparent cubic‐phase solid solution (Ho1–xLax)2O3 (where x = 0, 0.03, 0.05, 0.07, and 0.1) ceramics are sintered in a vacuum at 1780 °C for 3 h from nanopowders made by self‐propagating high‐temperature synthesis. The lanthana is proved to significantly influence the microstructure of the ceramics. The average crystallite sizes of the (Ho1–xLax)2O3 ceramics decrease with an increase in the concentration of lanthana. After vacuum sintering and low‐temperature annealing in air, the ceramics have second‐phase grains at the crystallite boundaries and the triple points. The volume fraction of the second phase is found to be in direct proportion to the lanthana content in the ceramics. This second phase is believed to be (Ho1–xLax)2O3 solid solutions with a higher lanthanum content in comparison with the surrounding crystallites. Annealing of the ceramics at 1500 °C for 2 h leads to the elimination of the second phase. [ABSTRACT FROM AUTHOR]

A sequence of F -polynomials { F K n (t , ℓ) } n = 1 ∞ of virtual knots K was defined by Kaur et al. in 2018. These polynomials have been expressed in terms of index value of crossing and n -writhe of K. By the construction, F -polynomials are generalizations of Kauffman's Affine Index Polynomial, and are invariants of virtual knot K. We present values of F -polynomials of oriented virtual knots having at most four classical crossings in a diagram. [ABSTRACT FROM AUTHOR]

RNA polymerase II (RNAPII) transcription is crucial for gene expression. RNAPII density peaks at gene boundaries, associating these key regions for gene expression control with limited RNAPII movement. The connections between RNAPII transcription speed and gene regulation in multicellular organisms are poorly understood. Here, we directly modulate RNAPII transcription speed by point mutations in the second largest subunit of RNAPII in Arabidopsis thaliana. A RNAPII mutation predicted to decelerate transcription is inviable, while accelerating RNAPII transcription confers phenotypes resembling auto‐immunity. Nascent transcription profiling revealed that RNAPII complexes with accelerated transcription clear stalling sites at both gene ends, resulting in read‐through transcription. The accelerated transcription mutant NRPB2‐Y732F exhibits increased association with 5′ splice site (5′SS) intermediates and enhanced splicing efficiency. Our findings highlight potential advantages of RNAPII stalling through local reduction in transcription speed to optimize gene expression for the development of multicellular organisms. Synopsis: RNAPII mutations that accelerate transcription cause auto‐immunity‐like phenotypes, read‐through transcription at RNAPII stalling sites and enhanced splicing in Arabidopsis, indicating that controlled transcription speed is required for optimal gene expression and plant development. A point mutation in RNAPII that increases the speed of RNAPII transcription triggers auto‐immunity‐like phenotypes.plaNET‐seq reveals reduced RNAPII stalling at gene boundaries in fast transcription mutants.Increasing the speed of transcription reduces the efficiency of transcriptional termination, resulting in read‐through transcription that blurs the spatial separation of genes.Accelerating RNAPII transcription enhances splicing efficiency in the multi‐cellular context. [ABSTRACT FROM AUTHOR]