1 What is a liquid crystal 2 1.1 Nematics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.2 Cholesterics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1.3 Smectics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1.4 Columnar phases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.5 Lyotropic liquid crystals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Introduction to Liquid Crystals

Up to 30% of patients with metastatic breast cancer eventually develop brain metastasis, yet the pathologic mechanism behind this development remains poorly understood. Here, we profiled long noncoding RNAs in brain metastatic tumors from patients with breast cancer and found that the X-inactive-specific transcript (XIST) was significantly downregulated in these tissues. XIST expression levels inversely correlated with brain metastasis, but not with bone metastasis in patients. Silencing of XIST preferentially promoted brain metastatic growth of XISThigh cells in our xenograft models. Moreover, knockout of XIST in mice mammary glands accelerated primary tumor growth as well as metastases in the brain. Decreased expression of XIST stimulated epithelial-mesenchymal transition and activated c-Met via MSN-mediated protein stabilization, which resulted in the promotion of stemness in the tumor cells. Loss of XIST also augmented secretion of exosomal miRNA-503, which triggered M1-M2 polarization of microglia. This M1-M2 conversion upregulated immune suppressive cytokines in microglia that suppressed T-cell proliferation. Furthermore, we screened an FDA-approved drug library and identified fludarabine as a synthetic lethal drug for XISTlow breast tumor cells and found that fludarabine blocked brain metastasis in our animal model. Our results indicate that XIST plays a critical role in brain metastasis in breast cancer by affecting both tumor cells and the tumor microenvironment and that the XIST-mediated pathway may serve as an effective target for treating brain metastasis.Significance: These findings describe mechanisms of how loss of the lncRNA XIST promotes brain metastasis in breast cancer and identify fludarabine as a potential therapeutic agent that specifically eliminates XISTlow tumor cells in the brain. Cancer Res; 78(15); 4316-30. ©2018 AACR.

/pdf/loss-of-xist-in-breast-cancer-activates-msn-c-met-and-1nwc9qwuro.pdf

Loss of XIST in Breast Cancer Activates MSN-c-Met and Reprograms Microglia via Exosomal miRNA to Promote Brain Metastasis

This paper compares charge transport across self-assembled monolayers (SAMs) of n-alkanethiols containing odd and even numbers of methylenes. Ultraflat template-stripped silver (AgTS) surfaces support the SAMs, while top electrodes of eutectic gallium−indium (EGaIn) contact the SAMs to form metal/SAM//oxide/EGaIn junctions. The EGaIn spontaneously reacts with ambient oxygen to form a thin (∼1 nm) oxide layer. This oxide layer enables EGaIn to maintain a stable, conical shape (convenient for forming microcontacts to SAMs) while retaining the ability to deform and flow upon contacting a hard surface. Conical electrodes of EGaIn conform (at least partially) to SAMs and generate high yields of working junctions. Ga2O3/EGaIn top electrodes enable the collection of statistically significant numbers of data in convenient periods of time. The observed difference in charge transport between n-alkanethiols with odd and even numbers of methylenes — the “odd−even effect” — is statistically discernible using these jun...

https://dash.harvard.edu/bitstream/handle/1/12967807/55252560.pdf?sequence=1

Odd-even effects in charge transport across self-assembled monolayers.

In addition to malignant cancer cells, tumors contain a variety of different stromal cells that constitute the tumor microenvironment. Some of these cell types provide crucial support for tumor growth, while others have been suggested to actually inhibit tumor progression. The composition of tumor microenvironment varies depending on the tumor site. The brain in particular consists of numerous specialized cell types such as microglia, astrocytes, and brain endothelial cells. In addition to these brain-resident cells, primary and metastatic brain tumors have also been shown to be infiltrated by different populations of bone marrow-derived cells. The role of different cell types that constitute tumor microenvironment in the progression of brain malignancies is only poorly understood. Tumor microenvironment has been shown to be a promising therapeutic target and diagnostic marker in extracranial malignancies. A better understanding of tumor microenvironment in the brain would therefore be expected to contribute to the development of improved therapies for brain tumors that are urgently required due to a poor availability of treatments for these malignancies. This review summarizes some of the known interactions between brain tumors and different stromal cells, and also discusses potential therapeutic approaches within this context.

https://www.mdpi.com/2072-6694/4/1/218/pdf

Tumor Microenvironment in the Brain

Perylene diimides (PDIs) are one class of the most explored organic fluorescent materials due to their high luminescence efficiency, optoelectronic properties, and ready to form well-tailored supramolecular structures. However, heavy aggregation caused quenching (ACQ) effect in solid state has greatly limited their potential applications. We have easily solved this problem by chemical modification of the PDI core with only phenoxy moietie at one of the bay position. In this paper, we report two perylene bisimides with small rigid substituents, 1- phenol -N, N’-dicyclohexyl perylene-3,4,9,10-tetracarboxylic diimide (PDI 1) and 1- p-chlorophenol-N, N’-dicyclohexyl perylene-3,4,9,10-tetracarboxylic diimide (PDI 2) possess both well defined organic nanostructures and high fluorescence quantum yield in the solid state. In contrast, 1-propanol-N, N’-dicyclohexyl perylene-3,4,9,10-tetracarboxylic diimide (PDI 3) bearing a straight chain only shown weak orange fluorescence. In addition, morphological inspection demonstrated that PDI 3 molecules easily form well-organized microstructures despite the linkage of the PDI core with a straight chain. The present strategy could provide a generic route towards novel and advanced fluorescent materials and these materials may find various applications in high-tech fields.

/pdf/self-assembly-optical-and-electrical-properties-of-perylene-23ypkflkss.pdf

Self-assembly, optical and electrical properties of perylene diimide dyes bearing unsymmetrical substituents at bay position

Using quantum mechanics and intermolecular forces, the molecular ordering of a nematogenic cyano-compound, 5-(trans-4-ethylcyclohexyl)-2-(4-cyanophenyl)-pyrimidine (ECCPP), has been examined. The CNDO/2 method has been employed to evaluate the net atomic charge and the dipole moment components at each atomic centre of the molecule. The configuration energy has been computed using the modified Rayleigh-Schrodinger perturbation method at intervals of 1A in translation and 10 in rotations, and corresponding probabilities have been calculated using Maxwell-Boltzmann statistics. The flexibility of various configurations has been studied in terms of the variation of the probability due to small departures from the most probable configuration. All possible geometrical arrangements between a molecular pair have been considered during stacking, in-plane and terminal interactions, and the most favourable configuration of pairing has been obtained. An attempt has been made to understand the behaviour of the molecules in terms of their relative order. The results have been compared with those obtained for other nematogens like DPAB [4,4 -di-n-propoxy-azoxybenzene] and EMBAC [ethyl 4-(4 -methoxybenzylidene amino) cinnamate].

/pdf/nematogenic-behaviour-of-a-cyano-compound-using-quantum-527zds3ymu.pdf

Nematogenic Behaviour of a Cyano-Compound Using Quantum Mechanics and Computer Simulations

In the present article, UV spectral characterization of a smectic-C liquid crystal 4,4′-bis(n-alkoxy)azoxybenzene (n = 14) (C40H66N2O3) has been carried out. Structure of the molecule has b...

UV spectral characterization of a smectic-C liquid crystal: Theoretical support to the experiment

Role of molecular rigidity on phase organization of a smectic liquid crystal—A theoretical model

Structure of nematogenic p-n-Alkoxy cinnamic acids (nOCAC) with various alkyl chain carbon atoms (n = 2, 4, 6, 8) has been optimized using density functional B3LYP with 6-31+G (d) basis set using crystallographic geometry as input. Using the optimized geometry, electronic structure of the molecules has been evaluated using the semiempirical methods and DFT calculations. Molecular charge distribution and phase stability of these systems have been analyzed based on Mulliken and Lowdin population analysis. The electronic absorption spectra of nOCAC molecules have been simulated by employing DFT method, semiempirical CNDO/S and INDO/S parameterizations. Two types of calculations have been performed for model systems containing single and double molecules of nOCAC. UV-Visible spectra have been calculated for all single molecules. The UV stability of the molecules has been discussed in light of the electronic transition oscillator strength (f). The dimer complexes of higher homologues (n = 6, 8) have also been reported to enable the comparison between single and double molecules.

Durga P. Ojha

Papers

Nematogenic Behaviour of a Cyano-Compound Using Quantum Mechanics and Computer Simulations

UV spectral characterization of a smectic-C liquid crystal: Theoretical support to the experiment

Role of molecular rigidity on phase organization of a smectic liquid crystal—A theoretical model

Structure and electronic absorption spectra of nematogenic alkoxycinnamic acids – a comparative study based on semiempirical and DFT methods

Calculation of spectral shifts in UV–visible region and photoresponsive behaviour of fluorinated liquid crystals: Effect of solvent and substituent