Molecular orientational distribution function of a chiral de Vries smectic liquid crystal from birefringence measurements.

An alternative method for determining the orientational distribution function and the order parameter from the electric field-induced birefringence measurements of a chiral liquid crystal compound in its Smectic A* is being introduced. A chiral mesogen based on a 5-phenyl-pyrimidine benzoate core terminated by a trisiloxane group on one side and the chiral alkyloxy chain on its opposite side is designed and synthesized to exhibit the "de Vries" smectic characteristics. The compound exhibits first order Smectic A*-Smectic C* phase transition, evidenced by the results of differential scanning calorimetry. The material is being investigated by electro-optical experiment in its smectic phases. We present a model that incorporates the generalised Langevin-Debye model which includes the Maier-Saupe effective mean-field potential term in order to explain the change in birefringence with the electric field. A good agreement between the experimental results and the predictions from the model leads to the determination of the molecular orientational distribution function in Smectic A phase. Furthermore, the temperature dependency of the Saupe orientational order parameter ⟨P2⟩ is obtained using the parameters of the model. Based on the experimental and theoretical results, we show that de Vries Smectic A* phase exhibits a broad volcano-like tilt angle distribution with the two maxima occurring at finite tilt angles closer to the Smectic A*-Smectic C* transition temperature, and a sugarloaf-like distribution occurs in the tilt for temperatures close to the Isotropic-Smectic A* phase transition.

Observation of the de Vries behavior in SmA* phase of a liquid crystal using polarised Raman scattering and infrared spectroscopy.

Two approaches exist in the literature for describing the orientational distribution function (ODF) of the molecular directors in SmA* phase of liquid crystals, though several models are recently proposed in the literature for explaining the de Vries behaviour. These ODFs correspond to either the conventional unimodal arrangements of molecular directors arising from the mean field theory that leads to the broad or sugar-loaf like distribution or to the "diffuse-cone-shaped" type distribution proposed by de Vries. The hypothesis by de Vries provides for a realistic explanation as to how at a molecular level, a first-order SmA* to SmC* transition can occur where the uniform molecular director azimuthal distributions condense to values lying within a narrow range of angles; finally these condense to a single value while at the same time ensuring a little or no concomitant shrinkage in the layer spacing. The azimuthal distribution of the in-layer directors is probed using IR and polarized Raman spectroscopic techniques. The latter allows us to obtain the ODF and the various order parameters for the uniaxial and the biaxial phases. Based on the results of these measurements, we conclude that the "cone-shaped" (or volcano-shaped) de Vries type of distribution can most preferably describe SmA* where "a first-order phase transition from SmA* to SmC*" and a low layer shrinkage can both be easily explained.

Role of salivary epithelial toll-like receptors 2 and 4 in modulating innate immune responses in chronic periodontitis.

BACKGROUND AND OBJECTIVE: Chronic periodontitis is initiated by sequential colonization with a broad array of bacteria and is perpetuated by an immune-inflammatory response to the changing biofilm. Host recognition of microbes is largely mediated by toll-like receptors (TLRs), which interact with conserved pathogen-associated molecular patterns. Based on ligand recognition, TLR-2 and TLR-4 interact with most periodontal pathogens. Extracrevicular bacterial reservoirs, such as the oral epithelial cells, contribute to the persistence of periodontitis. Human saliva is a rich source of oral epithelial cells that express functional TLRs. In this study we investigated the role of salivary epithelial cell (SEC) TLR-2 and TLR-4 in patients with generalized chronic periodontitis. MATERIAL AND METHODS: Unstimulated whole saliva (UWS) was collected from patients with generalized chronic periodontitis and from healthy individuals after obtaining informed consent. Epithelial cells isolated from each UWS sample were assessed for TLR-2, TLR-4, peptidoglycan recognition protein (PGRP)-3 and PGRP-4 by quantitative real-time PCR. In addition, the SECs were stimulated in vitro with microbial products for up to 24 h. The culture supernatant was assessed for cytokines by ELISA. RESULTS: Stimulation with TLR-2- or TLR-4-specific ligands induced cytokine secretion with differential kinetics and up-regulated TLR2 and TLR4 mRNAs, respectively, in cultures of SECs from patients with periodontitis. In addition, the SECs from patients with periodontitis exhibited reduced PGRP3 and PGRP4 mRNAs, the TLR-responsive genes with antibacterial properties. CONCLUSION: SECs derived from the UWS of patients with chronic periodontitis are phenotypically distinct and could represent potential resources for assessing the epithelial responses to periodontal pathogens in the course of disease progression and persistence.

Excitonic absorption and defect-related emission in three-dimensional MoS2 pyramids.

MoS2 micro-pyramids have demonstrated interesting properties in the fields of photonics and non-linear optics. In this work, we show the excitonic absorption and cathodoluminescence (CL) emission of MoS2 micro-pyramids grown by chemical vapor deposition (CVD) on SiO2 substrates. The excitonic absorption was obtained at room and cryogenic temperatures by taking advantage of the cathodoluminescence emission of the SiO2 substrate. We detected the CL emission related to defect intra-gap states, localized at the pyramid edges and with an enhanced intensity at the pyramid basal vertices. The photoluminescence and absorption analysis provided the Stokes shift of both the A and B excitons in the MoS2 pyramids. This analysis provides new insights into the optical functionality of MoS2 pyramids. This method can be applied to other 3D structures within the 2D materials family.

A Novel Hypergraph-Based Genetic Algorithm (HGGA) Built on Unimodular and Anti-homomorphism Properties for DNA Sequencing by Hybridization.

The sequencing by hybridization (SBH) of determining the order in which nucleotides should occur on a DNA string is still under discussion for enhancements on computational intelligence although the next generation of DNA sequencing has come into existence. In the last decade, many works related to graph theory-based DNA sequencing have been carried out in the literature. This paper proposes a method for SBH by integrating hypergraph with genetic algorithm (HGGA) for designing a novel analytic technique to obtain DNA sequence from its spectrum. The paper represents elements of the spectrum and its relation as hypergraph and applies the unimodular property to ensure the compatibility of relations between l-mers. The hypergraph representation and unimodular property are bound with the genetic algorithm that has been customized with a novel selection and crossover operator reducing the computational complexity with accelerated convergence. Subsequently, upon determining the primary strand, an anti-homomorphism is invoked to find the reverse complement of the sequence. The proposed algorithm is implemented in the GenBank BioServer datasets, and the results are found to prove the efficiency of the algorithm. The HGGA is a non-classical algorithm with significant advantages and computationally attractive complexity reductions ranging to [Formula: see text] with improved accuracy that makes it prominent for applications other than DNA sequencing like image processing, task scheduling and big data processing.

Elucidation of the de Vries behavior in terms of the orientational order parameter, apparent tilt angle, and field-induced tilt angle for smectic liquid crystals by polarized infrared spectroscopy.

We report experimental results of the orientational order parameter, the apparent tilt angle, and the field-induced tilt angle for three chiral smectic liquid crystalline materials investigated using infrared (IR) polarized spectroscopy. The common feature in these materials is use of the core 5-methyl-2- pyrimidine benzoate as the central part of the mesogen. This core is terminated by siloxane or carbosilane chains on one of the ends and by the chiral alkoxy chains on the opposite. These compounds exhibit low concomitant layer shrinkage at the smectic A^{*} (SmA^{*}) to smectic C^{*} (SmC^{*}) transition temperature and within the SmC^{*} phase itself. The maximum layer shrinkage in SmC^{*} is observed as ∼1.5%. We calculate the apparent orientational order parameter, S_{app} in the laboratory reference frame from the observed IR absorbance for homeotropic aligned samples, and the true order parameter, S, is calculated using the measured tilt angle and is also interpolated from Iso-SmA^{*} transition temperature closer to SmC^{*} phase. The apparent tilt angle in the SmA^{*} phase calculated from a comparison of order parameters S and S_{app} is found to be significantly large. A low magnitude of S_{app} found for homeotropic aligned samples in the SmA^{*} phase indicates that the order parameter plays a vital role in determining the de Vries characteristics, especially of exhibiting larger apparent tilt angles. Furthermore there is a significant increase in the true order parameter at temperatures close to SmA^{*} to SmC^{*} transition temperature in all three compounds. The planar-aligned samples are used to study the dependence of induced tilt angle on the applied electric field. The generalized Langevin-Debye model given by Shen et al. reasonably fits the experimental data on the field-induced tilt angle. The results show that the dipole moment of the tilt correlated domain in SmA^{*} diverges as temperature is lowered to the SmA^{*}-SmC^{*} transition temperature. The generalized Langevin-Debye model is also found to be extremely effective in confirming some of the conclusions of the de Vries behavior.

Specific inhibition of p300-HAT alters global gene expression and represses HIV replication.

Reversible acetylation of histone and nonhistone proteins plays pivotal role in cellular homeostasis. Dysfunction of histone acetyltransferases (HATs) leads to several diseases including cancer, neurodegenaration, asthma, diabetes, AIDS, and cardiac hypertrophy. We describe the synthesis and characterization of a set of p300-HAT-specific small-molecule inhibitors from a natural nonspecific HAT inhibitor, garcinol, which is highly toxic to cells. We show that the specific inhibitor selectively represses the p300-mediated acetylation of p53 in vivo. Furthermore, inhibition of p300-HAT down regulates several genes but significantly a few important genes are also upregulated. Remarkably, these inhibitors were found to be nontoxic to T cells, inhibit histone acetylation of HIV infected cells, and consequently inhibit the multiplication of HIV.

Human histone chaperone nucleophosmin enhances acetylation-dependent chromatin transcription.

Histone chaperones are a group of proteins that aid in the dynamic chromatin organization during different cellular processes. Here, we report that the human histone chaperone nucleophosmin interacts with the core histones H3, H2B, and H4 but that this histone interaction is not sufficient to confer the chaperone activity. Significantly, nucleophosmin enhances the acetylation-dependent chromatin transcription and it becomes acetylated both in vitro and in vivo. Acetylation of nucleophosmin and the core histones was found to be essential for the enhancement of chromatin transcription. The acetylated NPM1 not only shows an increased affinity toward acetylated histones but also shows enhanced histone transfer ability. Presumably, nucleophosmin disrupts the nucleosomal structure in an acetylation-dependent manner, resulting in the transcriptional activation. These results establish nucleophosmin (NPM1) as a human histone chaperone that becomes acetylated, resulting in the enhancement of chromatin transcription.

Histone chaperones in chromatin dynamics: implications in disease manifestation.

Histone chaperones are the histone interacting factors that stimulate histone transfer reaction without being a part of the final product. They are involved in the histone storage, histone translocation to the nucleus, and histone exchange and histone deposition onto the DNA for replication dependent chromatin assembly. Interestingly, they have also been demonstrated to possess the histone removal activity. While the involvement of the histone chaperones in chromatin transcription is undisputed, the question of their local versus global involvement is under scrutiny. This review enumerates the role played by various histone chaperones in the establishment of chromatin structure and regulation of chromatin transcription. The role of histone chaperones in disease manifestation is not very clear, preliminary results with few histone chaperones suggest that expression and function of these factors dramatically alters in carcinogenesis. This review will also focus on the possible role of histone chaperones in cancer diagnosis and progression

Small molecule modulators in epigenetics: implications in gene expression and therapeutics.

Altered gene expression resulting from changes in the post-translational modification patterns of the histones and DNA is collectively termed epigenetics. Such changes are inherited albeit there are no alterations in the DNA sequence. Epigenetic regulation of gene expression is implemented by a wide repertoire of histone and DNA modifying enzymes including the acetyltransferases and deacetylases, the methyltransferases and kinases among others. Therefore, a regulation of these enzyme activities affords a tighter regulation of gene expression. Conversely, aberrant enzymatic activities lead to unregulated gene expression, resulting in several diseases such as RTS (loss of CBP HAT activity) and Spinal and Bulbar muscular atrophy (HATs and HMTases), apart from several forms of cancers, particularly myeloid leukemia (RAR-PML or RAR-PLZF fusion proteins resulting in the mistargeting of HDACs). Thus these enzymes have emerged as novel targets for the design of therapeutics. In this direction, several small molecule modulators (activators and inhibitors) of HATs, HDACs and HMTases are being reported in literature. This chapter introduces the different histone modifying enzymes involved in gene regulation, their connection to disease manifestation and focuses on the role of small molecule modulators in understanding enzyme function and also the design and the evolution of chromatin therapeutics

Design and investigation of de Vries liquid crystals based on 5-phenyl-pyrimidine and (R,R)-2,3-epoxyhexoxy backbone.

Calamitic liquid crystals based on 5-phenyl-pyrimidine derivatives have been designed, synthesized, and characterized. The 5-phenyl pyrimidine core was functionalized with a chiral (R,R)-2,3-epoxyhexoxy chain on one side and either siloxane or perfluoro terminated chains on the opposite side. The one involving a perfluorinated chain shows SmA^{*} phase over a wide temperature range of 82 °C, whereas the siloxane analog exhibits both SmA^{*} and SmC^{*} phases over a broad range of temperatures, and a weak first-order SmA^{*}-SmC^{*} transition is observed. For the siloxane analog, the reduction factor for the layer shrinkage R (relative to its thickness at the SmA^{*}-SmC^{*} transition temperature, T_{AC}) is ∼0.373, and layer shrinkage is 1.7% at a temperature of 13 °C below the T_{AC}. This compound is considered to have "de Vries smectic" characteristics with the de Vries coefficient C_{deVries} of ∼0.86 on the scale of zero (maximum-layer shrinkage) to 1 (zero-layer shrinkage). A three-parameter mean-field model is introduced for the orientational distribution function (ODF) to reproduce the electro-optic properties. This model explains the experimental results and leads to the ODF, which exhibits a crossover from the sugar-loaf to diffuse-cone ODF some 3 °C above T_{AC}.

Chiral smectic-A and smectic-C phases with de Vries characteristics.

Infrared and dielectric spectroscopic techniques are used to investigate the characteristics of two chiral smectics, namely, 1,1,3,3,5,5,5-heptamethyltrisiloxane 1-[4^{'}-(undecyl-1-oxy)-4-biphenyl(S,S)-2-chloro-3-methylpentanoate] (MSi_{3}MR_{11}) and tricarbosilane-hexyloxy-benzoic acid (S)-4'-(1-methyl-hexyloxy)-3'-nitro-biphenyl-4-yl ester (W599). The orientational features and the field dependencies of the apparent tilt angle and the dichroic ratio for homogeneous planar-aligned samples were calculated from the absorbance profiles obtained at different temperatures especially in the smectic-A* phase of these liquid crystals. The dichroic ratios of the C-C phenyl ring stretching vibrations were considered for the determination of the tilt angle at different temperatures and different voltages. The low values of the order parameter obtained with and without an electric field applied across the cell in the Sm-A^{*} phase for both smectics are consistent with the de Vries concept. The generalized Langevin-Debye model introduced in the literature for explaining the electro-optical response has been applied to the results from infrared spectroscopy. The results show that the dipole moment of the tilt-correlated domain diverges as the transition temperature from Sm-A^{*} to Sm-C^{*} is approached. The Debye-Langevin model is found to be extremely effective in confirming some of the conclusions of the de Vries chiral smectics and gives additional results on the order parameter and the dichroic ratio as a function of the field across the cell. Dielectric spectroscopy finds large dipolar fluctuations in the Sm-A^{*} phase for both compounds and again these confirm their de Vries behavior.

Phase behavior and characterization of heptamethyltrisiloxane-based de Vries smectic liquid crystal by electro-optics, x rays, and dielectric spectroscopy.

A heptamethyltrisiloxane liquid crystal (LC) exhibiting I-SmA^{*}-SmC^{*} phases has been characterized by calorimetry, polarizing microscopy, x-ray diffraction, electro-optics, and dielectric spectroscopy. Observations of a large electroclinic effect, a large increase in the birefringence (Δn) with electric field, a low shrinkage in the layer thickness (∼1.75%) at 20 °C below the SmA^{*}-SmC^{*} transition, and low values of the reduction factor (∼0.40) suggest that the SmA^{*} phase in this material is of the de Vries type. The reduction factor is a measure of the layer shrinkage in the SmC^{*} phase and it should be zero for an ideal de Vries. Moreover, a decrease in the magnitude of Δn with decreasing temperature indicates the presence of the temperature-dependent tilt angle in the SmA^{*} phase. The electro-optic behavior is explained by the generalized Langevin-Debye model as given by Shen et al. [Y. Shen et al., Phys. Rev. E 88, 062504 (2013)10.1103/PhysRevE.88.062504]. The soft-mode dielectric relaxation strength shows a critical behavior when the system goes from the SmA^{*} to the SmC^{*} phase.

The current status of prophylactic femoral intramedullary nailing for metastatic cancer.

The most common site for cancer to spread is bone. At post-mortem, bony metastases have been found in 70% of patients dying from breast and prostate cancer. Due to the prevalence of cancer, bone metastasis and the associated management represents a huge burden on NHS resources. In patients with metastasis, around 56% of these involve the lower limb long bones. Due to the huge forces placed upon long bones during weight bearing, there is a high risk of fracture through areas of metastasis. It is reported that 23% of pathological fractures occur in the femoral subtrochanteric region. This area is subjected to forces up to four times the body weight, resulting in poor union rate for these fractures, and significant morbidity associated with difficulty in mobilising, and in patient nursing. As cancer treatments improve, the life expectancy in this subgroup of patients is likely to increase. Therefore medium-to-long-term management of these fractures, beyond the palliative, will become essential. We aim to evaluate the current management for metastatic malignant femoral disease, with particular focus on the prophylactic augmentation of diseased femorii using intramedullary nails.

Novel near-infrared emission from crystal defects in MoS2 multilayer flakes.

The structural defects in two-dimensional transition metal dichalcogenides, including point defects, dislocations and grain boundaries, are scarcely considered regarding their potential to manipulate the electrical and optical properties of this class of materials, notwithstanding the significant advances already made. Indeed, impurities and vacancies may influence the exciton population, create disorder-induced localization, as well as modify the electrical behaviour of the material. Here we report on the experimental evidence, confirmed by ab initio calculations, that sulfur vacancies give rise to a novel near-infrared emission peak around 0.75 eV in exfoliated MoS2 flakes. In addition, we demonstrate an excess of sulfur vacancies at the flake's edges by means of cathodoluminescence mapping, aberration-corrected transmission electron microscopy imaging and electron energy loss analyses. Moreover, we show that ripplocations, extended line defects peculiar to this material, broaden and redshift the MoS2 indirect bandgap emission.

Crystal and molecular structure of the antibiotic blasticidin S hydrochloride pentahydrate.

The three-dimensional structure of blasticidin S hydrochloride pentahydrate, a member of the cytosine amino nucleoside antibiotics, has been solved using diffractometer data and refined to an R value of 0.115. The crystal data are a = 13.500(5), b = 20.387(7), c = 4.824 A, beta = 98.66(3) degrees, Z = 2, Dc = 1.389 g .cm-3, space group P21. The nucleoside base conformation is anti(chi = 86 degrees) and the 2',3'-unsaturated pyranosyl sugar exhibits a half-chair (degree H5) conformation. The amide plane is twisted from the trans position by about 10 degrees. The guanidium group and the amino group of the amino acid chain are positively charged, while the carboxyl group of the sugar is ionized. The chloride ion is surrounded by water molecules only, in a trigonal prismatic arrangement. The molecule has an extended conformation and there is an intramolecular hydrogen bond between the ammonium group and the carboxyl group. A striking feature of blasticidin is that all the hydrophilic groups lie on one side of the molecule and the hydrophobic groups on the other. Amicetin also shows a similar feature and this might be linked to the commonality of their antibiotic functions. Hydrogen bonds link the hydrophilic sides of adjacent molecules forming double chains parallel to the b-axis. The hydrophobic sides of adjacent double chains are separated by a water layer.

Implications of small molecule activators and inhibitors of histone acetyltransferases in chromatin therapy.

Histone acetylation is a diagnostic feature of transcriptionally active chromatin. The group of enzymes, histone acetyltransferases (HATs), involved in this crucial step of gene regulation, covalently modifies the N-terminal lysine residues of histones by the addition of an acetyl group from acetyl coenzyme A. Dysfunction of these enzymes is often associated with several diseases, ranging from neurodegenerative disorders to cancer. These enzymes thus are potential new targets for therapeutics. We have discovered few small molecule compounds, which target HATs and either activate or inhibit the enzyme potently. These compounds would be useful as biological switching molecules for probing into the role of HATs in gene regulation and cell cycle and may be useful as new chemical entities for the development of new drugs.

An examination of the moisture sorption characteristics of commercial magnesium stearate.

The objective of this study was to characterize the moisture sorption of magnesium stearate and the morphological changes, if any, resulting from moisture sorption. Six samples of commercial magnesium stearate USP were examined. Moisture sorption isotherms were obtained at 25 degrees C and 5% to 98% relative humidity (RH) using a moisture balance. Changes in crystal form resulting from moisture sorption were determined by x-ray diffraction. There were differences in the shape of the isotherm, reversibility of moisture uptake, and shape of the hysteresis loop in the isotherms of crystalline and amorphous magnesium stearates. The isotherm of crystalline magnesium stearate was almost parallel to the pressure axis until an RH of ~80% was reached, when there was desorption of practically all of the adsorbed water. The isotherm of the amorphous sample was characterized by continuous uptake of water over the entire range of RH. Exposure of amorphous magnesium stearate to RH greater than 70% resulted in the formation of the trihydrate. The trihydrate was converted into the anhydrous form when heated to a temperature of 100 degrees C to 105 degrees C. The trihydrate could be generated by exposing the anhydrate to RH higher than 70%.

The effect of leg length discrepancy upon load distribution in the static phase (standing).

Leg length discrepancy (LLD) is commonly recognised as a complication of total hip arthroplasty. Some patients with only minor LLD complain of major difficulties. The effect of LLD has been described in the dynamic phase, but not static phase. The aim of this project was to investigate the effect of leg length discrepancy on static limb loading (i.e. Standing). A pedobarograph was used to measure the limb loading of 20 normal volunteers whilst changing the height of the other foot thus simulating a LLD. With both feet at the same level, the left limb took 54% of the load. When the right foot was lower, (simulating a long left leg), the left leg took 39% of the load. When the right foot was higher, (simulating a long right leg), the left leg took 65% of the load. A paired t-test comparison of the simulation with the level load showed a significant difference with P=0.002. Our results show that weight distribution increased in the shorter limb when LLD was simulated. This uneven distribution is likely to lead to premature fatigue when standing and may explain why some patients with LLD post hip arthroplasty have poorer outcomes.