Nuclear Positions Research Articles

Alchemical geometry relaxation.

We propose the relaxation of geometries throughout chemical compound space using alchemical perturbation density functional theory (APDFT). APDFT refers to perturbation theory involving changes in nuclear charges within approximate solutions to Schrödinger's equation. We give an analytical formula to calculate the mixed second order energy derivatives with respect to both nuclear charges and nuclear positions (named "alchemical force") within the restricted Hartree-Fock case. We have implemented and studied the formula for its use in geometry relaxation of various reference and target molecules. We have also analyzed the convergence of the alchemical force perturbation series as well as basis set effects. Interpolating alchemically predicted energies, forces, and Hessian to a Morse potential yields more accurate geometries and equilibrium energies than when performing a standard Newton-Raphson step. Our numerical predictions for small molecules including BF, CO, N2, CH4, NH3, H2O, and HF yield mean absolute errors of equilibrium energies and bond lengths smaller than 10 mHa and 0.01 bohr for fourth order APDFT predictions, respectively. Our alchemical geometry relaxation still preserves the combinatorial efficiency of APDFT: Based on a single coupled perturbed Hartree-Fock derivative for benzene, we provide numerical predictions of equilibrium energies and relaxed structures of all 17 iso-electronic charge-neutral BN-doped mutants with averaged absolute deviations of ∼27 mHa and ∼0.12 bohr, respectively.

Cytological Comparison between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma by Image Analysis Software Using Touch Smear Samples of Surgically Resected Specimens.

Simple SummaryThis study cytologically compared hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) using image analyzing software. The results indicated that the major/minor axis ratio of ICC was significantly larger than in HCC in Papanicolaou staining. This difference was consistently observed in clinical samples of cytology such as fine-needle aspiration, brushing and ascites. This study indicated a significant difference in the nuclear morphology of HCC (round shape) and ICC (oval shape) in Papanicolaou-stained cytology specimens. This simple and objective finding is considered to be useful for differential cytodiagnosis of HCC and ICC.To investigate useful cytological features for differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), this study cytologically compared HCC to ICC using image analysis software. Touch smear specimens of surgically resected specimens were obtained from a total of 61 nodules of HCC and 16 of ICC. The results indicated that the major/minor axis ratio of ICC is significantly larger than that of HCC (1.67 ± 0.27 vs. 1.32 ± 0.11, p < 0.0001) in Papanicolaou staining. This result means that the nucleus of HCC is close to round and the nucleus of ICC is close to an oval. This significant difference in the major/minor axis ratio between ICC and HCC was consistently observed by the same analyses using clinical samples of cytology (4 cases of HCC and 13 cases of ICC) such a fine-needle aspiration, brushing and ascites (ICC: 1.45 ± 0.13 vs. HCC: 1.18 ± 0.056, p = 0.004). We also confirmed that nuclear position center-positioned nucleus (p < 0.0001) and granular cytoplasm (p < 0.0001) are typical features of HCC tumor cells compared to ICC tumor cells. The research study found a significant difference in the nuclear morphology of HCC (round shape) and ICC (oval shape) in Papanicolaou-stained cytology specimens. This simple and objective finding will be very useful for the differential cytodiagnosis of HCC and ICC.

Single-molecule tracking (SMT) and localization of SRF and MRTF transcription factors during neuronal stimulation and differentiation.

In cells, proteins encoded by the same gene do not all behave uniformly but engage in functional subpopulations induced by spatial or temporal segregation. While conventional microscopy has limitations in revealing such spatial and temporal diversity, single-molecule tracking (SMT) microscopy circumvented this problem and allows for high-resolution imaging and quantification of dynamic single-molecule properties. Particularly in the nucleus, SMT has identified specific DNA residence times of transcription factors (TFs), DNA-bound TF fractions and positions of transcriptional hot-spots upon cell stimulation. By contrast to cell stimulation, SMT has not been employed to follow dynamic TF changes along stages of cell differentiation. Herein, we analysed the serum response factor (SRF), a TF involved in the differentiation of many cell types to study nuclear single-molecule dynamics in neuronal differentiation. Our data in living mouse hippocampal neurons show dynamic changes in SRF DNA residence time and SRF DNA-bound fraction between the stages of adhesion, neurite growth and neurite differentiation in axon and dendrites. Using TALM (tracking and localization microscopy), we identified nuclear positions of SRF clusters and observed changes in their numbers and size during differentiation. Furthermore, we show that the SRF cofactor MRTF-A (myocardin-related TF or MKL1) responds to cell activation by enhancing the long-bound DNA fraction. Finally, a first SMT colocalization study of two proteins was performed in living cells showing enhanced SRF/MRTF-A colocalization upon stimulation. In summary, SMT revealed modulation of dynamic TF properties during cell stimulation and differentiation.

Chemistry without the Born-Oppenheimer approximation.

Chemistry without the Born-Oppenheimer approximation.

Materials for Sustainable Nuclear Energy: A European Strategic Research and Innovation Agenda for All Reactor Generations

Nuclear energy is presently the single major low-carbon electricity source in Europe and is overall expected to maintain (perhaps eventually even increase) its current installed power from now to 2045. Long-term operation (LTO) is a reality in essentially all nuclear European countries, even when planning to phase out. New builds are planned. Moreover, several European countries, including non-nuclear or phasing out ones, have interests in next generation nuclear systems. In this framework, materials and material science play a crucial role towards safer, more efficient, more economical and overall more sustainable nuclear energy. This paper proposes a research agenda that combines modern digital technologies with materials science practices to pursue a change of paradigm that promotes innovation, equally serving the different nuclear energy interests and positions throughout Europe. This paper chooses to overview structural and fuel materials used in current generation reactors, as well as their wider spectrum for next generation reactors, summarising the relevant issues. Next, it describes the materials science approaches that are common to any nuclear materials (including classes that are not addressed here, such as concrete, polymers and functional materials), identifying for each of them a research agenda goal. It is concluded that among these goals are the development of structured materials qualification test-beds and materials acceleration platforms (MAPs) for materials that operate under harsh conditions. Another goal is the development of multi-parameter-based approaches for materials health monitoring based on different non-destructive examination and testing (NDE&amp;T) techniques. Hybrid models that suitably combine physics-based and data-driven approaches for materials behaviour prediction can valuably support these developments, together with the creation and population of a centralised, “smart” database for nuclear materials.

Spatial and Genomic Correlates of HIV-1 Integration Site Targeting.

HIV-1 integrase and capsid proteins interact with host proteins to direct preintegration complexes to active transcription units within gene-dense regions of chromosomes for viral DNA integration. Analyses of spatially-derived genomic DNA coordinates, such as nuclear speckle-associated domains, lamina-associated domains, super enhancers, and Spatial Position Inference of the Nuclear (SPIN) genome states, have further informed the mechanisms of HIV-1 integration targeting. Critically, however, these different types of genomic coordinates have not been systematically analyzed to synthesize a concise description of the regions of chromatin that HIV-1 prefers for integration. To address this informational gap, we have extensively correlated genomic DNA coordinates of HIV-1 integration targeting preferences. We demonstrate that nuclear speckle-associated and speckle-proximal chromatin are highly predictive markers of integration and that these regions account for known HIV biases for gene-dense regions, highly transcribed genes, as well as the mid-regions of gene bodies. In contrast to a prior report that intronless genes were poorly targeted for integration, we find that intronless genes in proximity to nuclear speckles are more highly targeted than are spatially-matched intron-containing genes. Our results additionally highlight the contributions of capsid and integrase interactions with respective CPSF6 and LEDGF/p75 host factors in these HIV-1 integration targeting preferences.

Propagation and Parametric Amplification in Four-Wave Mixing Processes: Intramolecular Coupling and High-Order Effects

A strong pump-power dependence of the four-wave mixing (FWM) signal for an aqueous solution of Malachite green is reported. The characteristics of the pump-power dependence of the nonlinear signal are reproduced by a theoretical model based on the coupling between pump-probe, considering signal fields and propagation effects. The effect of the intramolecular coupling on the nonlinear intensity of the FWM signal is studied using a model molecule consisting of two-coupled harmonic curves of electronic energies with minima displaced in energy and nuclear positions. Two-vibrational states are considered while including non-adiabatic effects for the two-state model. Moreover, the coupling among the field components, as well as the propagation effects, are studied by considering a constant pump-intensity. Our calculation scheme, considering both the intramolecular coupling effects in the description of the molecular structure and the effects produced by the propagation of the FWM signal along the optical length, allows the exponential dependence of the latter, as the intensity of the pumping beam increases. Our treatments do not require the inclusion of other non-resonant processes outside the RWA approximation, due to the consideration of an adiabatic basis.

Aster repulsion drives short-ranged ordering in the Drosophila syncytial blastoderm

Biological systems are highly complex, yet notably ordered structures can emerge. During syncytial stage development of the Drosophila melanogaster embryo, nuclei synchronously divide for nine cycles within a single cell, after which most of the nuclei reach the cell cortex. The arrival of nuclei at the cortex occurs with remarkable positional order, which is important for subsequent cellularisation and morphological transformations. Yet, the mechanical principles underlying this lattice-like positional order of nuclei remain untested. Here, using quantification of nuclei position and division orientation together with embryo explants, we show that short-ranged repulsive interactions between microtubule asters ensure the regular distribution and maintenance of nuclear positions in the embryo. Such ordered nuclear positioning still occurs with the loss of actin caps and even the loss of the nuclei themselves; the asters can self-organise with similar distribution to nuclei in the wild-type embryo. The explant assay enabled us to deduce the nature of the mechanical interaction between pairs of nuclei. We used this to predict how the nuclear division axis orientation changes upon nucleus removal from the embryo cortex, which we confirmed in vivo with laser ablation. Overall, we show that short-ranged microtubule-mediated repulsive interactions between asters are important for ordering in the early Drosophila embryo and minimising positional irregularity.

A Novel Hyperactive Nud1 Mitotic Exit Network Scaffold Causes Spindle Position Checkpoint Bypass in Budding Yeast.

Mitotic exit is a critical cell cycle transition that requires the careful coordination of nuclear positioning and cyclin B destruction in budding yeast for the maintenance of genome integrity. The mitotic exit network (MEN) is a Ras-like signal transduction pathway that promotes this process during anaphase. A crucial step in MEN activation occurs when the Dbf2-Mob1 protein kinase complex associates with the Nud1 scaffold protein at the yeast spindle pole bodies (SPBs; centrosome equivalents) and thereby becomes activated. This requires prior priming phosphorylation of Nud1 by Cdc15 at SPBs. Cdc15 activation, in turn, requires both the Tem1 GTPase and the Polo kinase Cdc5, but how Cdc15 associates with SPBs is not well understood. We have identified a hyperactive allele of NUD1, nud1-A308T, that recruits Cdc15 to SPBs in all stages of the cell cycle in a CDC5-independent manner. This allele leads to early recruitment of Dbf2-Mob1 during metaphase and requires known Cdc15 phospho-sites on Nud1. The presence of nud1-A308T leads to loss of coupling between nuclear position and mitotic exit in cells with mispositioned spindles. Our findings highlight the importance of scaffold regulation in signaling pathways to prevent improper activation.

The role of the semantheme “Heart” in the structure of the field “Spiritual state” (based on the material of the Russian language)

The article deals with the question of denotative space of spiritual state concepts, analyzes the semantic structure of the lexeme ‘Heart’, author makes attempts to reconstruct the semantheme ‘Heart’, what is based on the lexicographic dictionaries data, contexts usage and stable combinations. The nests of semanthems, where each semantic feature of the stratified complex was acted as dominant, are also analyzed. Thus at the level of language prototypes and at the level of implementation of these prototypes in the language an attempt to fully describe the structure of the semantheme “Heart” is complete. The author drew attention to the texts of the early historical era, where it was noticed that abstract concepts at the language level were denoted using the lexical block “Heart”, but at the present stage of language development all these concepts have a separate lexeme. This observation gave the author the opportunity to assert that the “Heart” is one of the first semanthems in the spiritual sector of the system “Man”. Based on the analysis, author is stated that in the hierarchy of the spiritual sector of the system “Man” semantheme 'Heart' occupies a nuclear position, it is initial nominator of the specific reaction of the heart as an organ, later it spread the field of meaning in the direction of three other basic meanings – thoughts/feelings/desires, which gave the language consciousness the opportunity to build all subsequent abstract concepts, nuclear generalized features of the semantheme 'heart' can be found in the semantic structure of the lexical units, nominating the sphere of spirituality. The study of the semantheme ‘Heart’ paved the way for the possibility of a new vision to the vocabulary of emotions and mental states in general denotative space. The author suggests including to the denotative space the assessment of the phenomenon by the participant, the intensity of the manifestation of the heart reaction, the intensity of desire, facial or effective reaction. It is proposed to specify the intensity using a scale with positive and negative indicators.

Accurate 57Fe Mössbauer Parameters from General Gaussian Basis Sets.

The prediction of isomer shifts in 57Fe Mossbauer spectra is typically achieved by building calibration lines using the values of the density at the nuclear position. Using Slater-type orbital basis or large and specific Gaussian-type orbital basis has been thus far mandatory to achieve accurate predictions with density functional theory methods. In this work, we show that replacing the value of the density at the nucleus by the density integrated in a sphere of radius 0.06 au centered on the Fe nuclei yields excellent calibration lines (r2 = 0.976) with a high predictive power (q2 = 0.975, MAE = 0.055 mm·s–1) while using the conventional def2-TZVP basis set and X-ray geometrical parameters. Our data set comprises 69 57Fe-containing compounds and 103 signals. We also find B3LYP performing significantly better than the PW91 functional.

Investigation of quantum effect of liquid hydrogen on homogeneous bubble nucleation using a density functional theory and molecular dynamics simulations

In this paper, a quantum effect of hydrogen molecules (uncertainties of each atomic nuclear position and momentum) on the bubble nucleation rate was investigated. The homogeneous bubble nucleation analyses were performed using a density functional theory (DFT) reflecting equations of state (EOSs) constructed to reproduce the thermophysical properties of hydrogen obtained from a classical molecular dynamics (MD) method and a quantum MD method. The results showed that the quantum nature of liquid hydrogen decreases the bubble nucleation rate when compared in the same reduced temperature and reduced superheat ratio condition. Further, it was indicated that the results might be caused by the increase of the energy barrier arising from the difference of the density profile and its position at the critical bubble (in other words, the differences of the critical bubble size and the liquid–vapor interface thickness). Furthermore, the DFT analysis was validated through the evaluation of the bubble nucleation rate using the classical MD method and the quantum MD method made as numerical experiments, and qualitatively the same result was obtained between the DFT and the MD simulations.

Auxin-dependent control of cytoskeleton and cell shape regulates division orientation in the Arabidopsis embryo

SummaryPremitotic control of cell division orientation is critical for plant development, as cell walls prevent extensive cell remodeling or migration. While many divisions are proliferative and add cells to existing tissues, some divisions are formative and generate new tissue layers or growth axes. Such formative divisions are often asymmetric in nature, producing daughters with different fates. We have previously shown that, in the Arabidopsis thaliana embryo, developmental asymmetry is correlated with geometric asymmetry, creating daughter cells of unequal volume. Such divisions are generated by division planes that deviate from a default “minimal surface area” rule. Inhibition of auxin response leads to reversal to this default, yet the mechanisms underlying division plane choice in the embryo have been unclear. Here, we show that auxin-dependent division plane control involves alterations in cell geometry, but not in cell polarity axis or nuclear position. Through transcriptome profiling, we find that auxin regulates genes controlling cell wall and cytoskeleton properties. We confirm the involvement of microtubule (MT)-binding proteins in embryo division control. Organization of both MT and actin cytoskeleton depends on auxin response, and genetically controlled MT or actin depolymerization in embryos leads to disruption of asymmetric divisions, including reversion to the default. Our work shows how auxin-dependent control of MT and actin cytoskeleton properties interacts with cell geometry to generate asymmetric divisions during the earliest steps in plant development.

A stochastic model of homeostasis: The roles of noise and nuclear positioning in deciding cell fate

SummaryWe study a population-based cellular model that starts from a single stem cell that divides stochastically to give rise to either daughter stem cells or differentiated daughter cells. There are three main components in the model: nucleus position, the underlying gene-regulatory network, and stochastic segregation of transcription factors in the daughter cells. The proportion of self-renewal and differentiated cell lines as a function of the nucleus position which in turn decides the plane of cleavage is studied. Both nuclear position and noise play an important role in determining the stem cell genealogies. We have observed both long and short genealogies in model simulation, and these compare well with experimental results from neuroblast and B-cell division. Symmetric divisions are observed in apical nuclei, while asymmetric division occurs when the nucleus is toward the base. In this model, the number of clones decreases over time, although the average clone size increases.

Systematic review of the genus Ostracodinium (Ciliophora, Entodiniomorphida, Ophryoscolecidae) and notes on the taxonomy of Ostracodinium rugoloricatum Kofoid amp; MacLennan, 1932.

The family Ophryoscolecidae (Ciliophora, Entodiniomorphida) constitutes a diverse and monophyletic group of symbiotic ciliates of herbivorous mammals. The family includes approximately 200 species, distributed in three subfamilies and sixteen genera. The subfamily Diplodiniinae is the most diverse group in Ophryoscolecidae and comprises the genus Ostracodinium, which includes species with two retractable ciliary zones in the anterior body portion, a broad skeletal plate covering almost all the right surface of the body and a variable number of contractile vacuoles. The genus currently comprises 28 species, classified according to body size and shape, position and shape of the nuclear apparatus, number and position of contractile vacuoles, and number and shape of caudal projections. The present study performs a systematic review of the genus Ostracodinium, based on morphological and molecular data, and provides data about geographic distribution and hosts of each species.

Small intestinal mucosal cells in piglets fed with probiotic and zinc: a qualitative and quantitative microanatomical study.

Probiotics and zinc are commonly used and beneficial in pig production. This work aimed to assess the effects of probiotic and zinc on the mucosal cells of the small intestine in respect to digestive capacity and immunity in pre- and post-weaned piglets. Eighteen Large White Yorkshire piglets were divided equally into control and treatment groups. The piglets were maintained in standard management conditions and were weaned at 28 days of age. The treatment group of piglets fed a mixture of probiotics orally at 1.25 × 109 CFU/day and zinc at 2000 ppm/day from birth to 10 days of age. At three different age-groups viz. day 20 (pre-weaning) and, day 30 and day 60 (post-weaning), the animals were sacrificed. For histomorphology, the tissue samples were processed and stained with Mayer's haematoxylin and eosin for routine study, combined periodic acid-Schiff-Alcian blue for mucopolysaccharides and Masson-Hamperl argentaffin technique for argentaffin cells. The stained slides were observed under the microscope. The samples were processed as per the standard procedure for scanning and transmission electron microscopy. The statistical analysis of the data using the appropriate statistical tests was also conducted. The mucosal epithelium of villi and crypts were lined by enterocytes, goblet cells, argentaffin cells, microfold (M-cell) cells, tuft cells and intraepithelial lymphocytes. The multipotent stem cells were located at the crypt base. The length of the enterocyte microvilli was significantly longer (p < 0.05) in the treatment group of piglets. The number of different types of goblet cells and argentaffin cells was more in treated piglets irrespective of segments of intestine and age. The intraepithelial lymphocytes were located in apical, nuclear and basal positions in the lining epithelium of both villus tip and base with their significant increase in the treatment group of piglets. The transmission electron microscopy revealed the frequent occurrence of tuft cells in the lining mucosa of the small intestine in treated piglets. Dietary supplementation of probiotic and zinc induced the number of different mucosal cells of villi and crypts in the small intestine that might suggest the greater absorptive capacity of nutrients and effective immunity in critical pre and post-weaned piglets.

Energy, Structures, and Response Properties with a Fully Coupled QM/AMOEBA/ddCOSMO Implementation.

We present the implementation of a fully coupled polarizable QM/MM/continuum model based on the AMOEBA polarizable force field and the domain decomposition implementation of the conductor-like screening model. Energies, response properties, and analytical gradients with respect to both QM and MM nuclear positions are available, and a generic, atomistic cavity can be employed. The model is linear scaling in memory requirements and computational cost with respect to the number of classical atoms and is therefore suited to model large, complex systems. Using three variants of the green-fluorescent protein, we investigate the overall computational cost of such calculations and the effect of the continuum model on the convergence of the computed properties with respect to the size of the embedding. We also demonstrate the fundamental role of polarization effects by comparing polarizable and nonpolarizable embeddings to fully QM ones.

Structural Peculiarities of Units in the Professional Sublanguage of Fire Protection Services

The article shows the results of an original study aimed at identifying structural characteristics of non-codified units in the professional sublanguage of fire protection services. The authors carry out a comparative analysis of these features and present the structural and linguistic classification of the units in the Russian and English variants of the given sublanguage. It is stated that there is symmetry of the structural and linguistic parametres of the nuclear and peripheral groups including standard units of I and II levels, the nuclear position is occupied by nouns and substantive phrases. The most productive model of multi-word units in the Russian and English variants of the fire protection services’ professional sublanguage is a model consisting of an adjunct element expressed by adjectives or nouns and a kernel represented by nouns.

Molecular vibrational frequencies from analytic Hessian of constrained nuclear-electronic orbital density functional theory.

Nuclear quantum effects are important in a variety of chemical and biological processes. The constrained nuclear-electronic orbital density functional theory (cNEO-DFT) has been developed to include nuclear quantum effects in energy surfaces. Herein, we develop the analytic Hessian for cNEO-DFT energy with respect to the change in nuclear (expectation) positions, which can be used to characterize stationary points on energy surfaces and compute molecular vibrational frequencies. This is achieved by constructing and solving the multicomponent cNEO coupled-perturbed Kohn-Sham (cNEO-CPKS) equations, which describe the response of electronic and nuclear orbitals to the displacement of nuclear (expectation) positions. With the analytic Hessian, the vibrational frequencies of a series of small molecules are calculated and compared to those from conventional DFT Hessian calculations as well as those from the vibrational second-order perturbation theory (VPT2). It is found that even with a harmonic treatment, cNEO-DFT significantly outperforms DFT and is comparable to DFT-VPT2 in the description of vibrational frequencies in regular polyatomic molecules. Furthermore, cNEO-DFT can reasonably describe the proton transfer modes in systems with a shared proton, whereas DFT-VPT2 often faces great challenges. Our results suggest the importance of nuclear quantum effects in molecular vibrations, and cNEO-DFT is an accurate and inexpensive method to describe molecular vibrations.

Femtosecond responses of hydrated DNA irradiated by ionizing rays focus on the sugar-phosphate part

In this article, we investigate the mechanisms of DNA ionization upon irradiation by 0.5 meV alpha particles. We focus on the sugar-phosphate group and its hydration shell. In radiation chemistry, the term quasi-direct effect refers the physical and chemical responses taking place after irradiation of solvent molecules pertaining to the solvation shells of solutes. The molecular mechanisms accounting for the quasi-direct effect are actually largely elusive, especially for those prevailing in the early timescales (< 10–12 s). We report Real-Time Time-Dependent Auxiliary Density Functional Theory simulations carried out within the framework of hybrid QM/MM scheme (Quantum Mechanics/Molecular Mechanics) with polarizable and non-polarizable embedding. Ten water molecules from the solvation shell of DNA backbone are independently irradiated. We find that during the first femtoseconds after irradiation, the holes formed on the irradiated water remain at their sites of formation. Electrostatic induction within the environment does not significantly impact charge migrations. We address the hypothesis that charge migration driven by electron correlation is responsible for an ultrafast H2O+ to DNA charge transfers, which would account for a quasi-direct effect. We find that pure charge migration at fixed nuclear positions is not responsible for the quasi-direct effect when considering sugar-phosphate solvation shells.