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Supplementary Data from Upregulation of MMP-2 by HMGA1 Promotes Transformation in Undifferentiated, Large-Cell Lung Cancer

Although lung cancer is the leading cause of cancer death worldwide, the precise molecular mechanisms that give rise to lung cancer are incompletely understood. Here, we show that HMGA1 is an important oncogene that drives transformation in undifferentiated, large-cell carcinoma. First, we show that the HMGA1 gene is overexpressed in lung cancer cell lines and primary human lung tumors. Forced overexpression of HMGA1 induces a transformed phenotype with anchorage-independent cell growth in cultured lung cells derived from normal tissue. Conversely, inhibiting HMGA1 expression blocks anchorage-independent cell growth in the H1299 metastatic, undifferentiated, large-cell human lung carcinoma cells. We also show that the matrix metalloproteinase-2 (MMP-2) gene is a downstream target upregulated by HMGA1 in large-cell carcinoma cells. In chromatin immunoprecipitation experiments, HMGA1 binds directly to the MMP-2 promoter in vivo in large-cell lung cancer cells, but not in squamous cell carcinoma cells. In large-cell carcinoma cell lines, there is a significant, positive correlation between HMGA1 and MMP-2 mRNA. Moreover, interfering with MMP-2 expression blocks anchorage-independent cell growth in H1299 large-cell carcinoma cells, indicating that the HMGA1–MMP-2 pathway is required for this transformation phenotype in these cells. Blocking MMP-2 expression also inhibits migration and invasion in the H1299 large-cell carcinoma cells. Our findings suggest an important role for MMP-2 in transformation mediated by HMGA1 in large-cell, undifferentiated lung carcinoma and support the development of strategies to target this pathway in selected tumors. (Mol Cancer Res 2009;7(11):1803–12)

Supplementary Table 1 from The High-Mobility Group A1a/Signal Transducer and Activator of Transcription-3 Axis: An Achilles Heel for Hematopoietic Malignancies?

Supplementary Table 1 and Figure Legend from Blockade of Hedgehog Signaling Inhibits Pancreatic Cancer Invasion and Metastases: A New Paradigm for Combination Therapy in Solid Cancers

Supplementary Figure 1 from Blockade of Hedgehog Signaling Inhibits Pancreatic Cancer Invasion and Metastases: A New Paradigm for Combination Therapy in Solid Cancers

Supplementary Figures 1-3 from The High-Mobility Group A1 Gene Up-Regulates Cyclooxygenase 2 Expression in Uterine Tumorigenesis

Supplementary Table 2 from The High-Mobility Group A1a/Signal Transducer and Activator of Transcription-3 Axis: An Achilles Heel for Hematopoietic Malignancies?

Invasive pancreatic cancer is thought to develop through a series of noninvasive duct lesions known as pancreatic intraepithelial neoplasia (PanIN). We used cDNA microarrays interrogating 15,000 transcripts to identify 49 genes that were differentially expressed in microdissected early PanIN lesions (PanIN-1B/2) compared with microdissected normal duct epithelium. In this analysis, a cluster of extrapancreatic foregut markers, including pepsinogen C, MUC6, KLF4, and TFF1, was found to be up-regulated in PanIN. Up-regulation of these genes was further validated using combinations of real-time reverse transcription-PCR, in situ hybridization, and immunohistochemistry in a total of 150 early PanIN lesions from 81 patients. Identification of these gastrointestinal transcripts in human PanIN prompted assessment of other foregut markers by both semiquantitative and real-time reverse transcription-PCR, revealing similar up-regulation of Sox-2, Gastrin, HoxA5, GATA4/5/6, Villin and Forkhead 6 (Foxl1). In contrast to frequent expression of multiple gastric epithelial markers, the intestinal markers intestinal fatty acid binding protein, CDX1 and CDX2 were rarely expressed either in PanIN lesions or in invasive pancreatic cancer. Hedgehog pathway activation induced by transfection of immortalized human pancreatic ductal epithelial cells with Gli1 resulted in up-regulation of the majority of foregut markers seen in early PanIN lesions. These data show frequent up-regulation of foregut markers in early PanIN lesions and suggest that PanIN development may involve Hedgehog-mediated conversion to a gastric epithelial differentiation program.

Supplementary Table 2 from Gene Expression Profiles in Pancreatic Intraepithelial Neoplasia Reflect the Effects of Hedgehog Signaling on Pancreatic Ductal Epithelial Cells

In the context of pancreatic cancer, metastasis remains the most critical determinant of resectability, and hence survival. The objective of this study was to determine whether Hedgehog (Hh) signaling plays a role in pancreatic cancer invasion and metastasis because this is likely to have profound clinical implications. In pancreatic cancer cell lines, Hh inhibition with cyclopamine resulted in down-regulation of snail and up-regulation of E-cadherin, consistent with inhibition of epithelial-to-mesenchymal transition, and was mirrored by a striking reduction of in vitro invasive capacity (P < 0.0001). Conversely, Gli1 overexpression in immortalized human pancreatic ductal epithelial cells led to a markedly invasive phenotype (P < 0.0001) and near total down-regulation of E-cadherin. In an orthotopic xenograft model, cyclopamine profoundly inhibited metastatic spread; only one of seven cyclopamine-treated mice developed pulmonary micrometastases versus seven of seven mice with multiple macrometastases in control animals. Combination of gemcitabine and cyclopamine completely abrogated metastases while also significantly reducing the size of “primary” tumors. Gli1 levels were up-regulated in tissue samples of metastatic human pancreatic cancer samples compared with matched primary tumors. Aldehyde dehydrogenase (ALDH) overexpression is characteristic for both hematopoietic progenitors and leukemic stem cells; cyclopamine preferentially reduced “ALDH-high” cells by ∼3-fold (P = 0.048). We confirm pharmacologic Hh pathway inhibition as a valid therapeutic strategy for pancreatic cancer and show for the first time its particular efficacy against metastatic spread. By targeting specific cellular subpopulations likely involved in tumor initiation at metastatic sites, Hh inhibitors may provide a new paradigm for therapy of disseminated malignancies, particularly when used in combination with conventional antimetabolites that reduce “bulk” tumor size. [Cancer Res 2007;67(5):2187–96]

Uterine cancer is the most common cancer of the female genital tract and is the fourth most frequent cause of cancer death in women in the U.S. Despite the high prevalence of uterine cancers, the molecular events that lead to neoplastic transformation in the uterus are poorly understood. Moreover, there are limited mouse models to study these malignancies. We generated transgenic mice with high-mobility group A1 gene (HMGA1a) expression targeted to uterine tissue and all female mice developed tumors by 9 months of age. Histopathologically, the tumors resemble human uterine adenosarcoma and are transplantable. To determine whether these findings are relevant to human disease, we evaluated primary human uterine neoplasms and found that HMGA1a mRNA and protein levels are increased in most high-grade neoplasms but not in normal uterine tissue, benign tumors, or most low-grade neoplasms. We also found that HMGA1a up-regulates cyclooxygenase 2 (COX-2) expression in transgenic tumors. Moreover, both HMGA1a and COX-2 expression are up-regulated in high-grade human leiomyosarcomas. Using chromatin immunoprecipitation, HMGA1a binds directly to the COX-2 promoter in human uterine cancer cells in vivo and activates its expression in transfection experiments. We also show that blocking either HMGA1a or COX-2 in high-grade human uterine cancer cells blocks anchorage-independent cell growth in methylcellulose. These findings show that HMGA1a functions as an oncogene when overexpressed in the uterus and contributes to the pathogenesis of human uterine cancer by activating COX-2 expression. Although a larger study is needed to confirm these results, HMGA1a may be a useful marker for aggressive human uterine cancers. [Cancer Res 2007;67(9):3998–4004]

"de Vries" liquid crystals, defined by a maximum layer shrinkage of ≤1% from the smectic A to C phase transition, are an integral component of ferroelectric liquid crystal (FLC) displays. Bona fide de Vries materials described in the literature are primarily perfluorinated, polysiloxane and polysilane-terminated rod-like (or calamitic) LCs. Herein, for the first time, we report a series of newly designed achiral unsymmetrical bent-core molecules with terminal alkoxy chains exhibiting similar properties to "de Vries" LCs. The new molecular structure is based on the systematic distribution of four phenyl rings attached

We study DC and AC electrophoresis of silica nano and microrods in a thin film of a nematic liquid crystal. These particles induce virtual topological defects and demonstrate nontrivial electrophoresis. We measure several electrophoretic mobility coefficients and compare with those calculated theoretically. We demonstrate a competing effect of elastic and electrostatic torques that arises due to tilting of the rods in the liquid crystal. A simple theory describing this effect allows us to measure the effective polarisability of the rods. Our approach is simple and applicable to a wide variety of asymmetric and polarisable particles.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) is a complex ecosystem that drives tumor progression; however, in-depth single cell characterization of the PDAC TME and its role in response to therapy is lacking. We performed single-cell RNA sequencing on freshly collected human PDAC samples either before or after chemotherapy. Overall, we found a heterogeneous mixture of basal and classical cancer cell subtypes, along with distinct cancer-associated fibroblast and macrophage subpopulations. Strikingly, classical and basal-like cancer cells exhibited similar transcriptional responses to chemotherapy, and did not demonstrate a shift towards a basal-like transcriptional program among treated samples. We observed decreased ligand-receptor interactions in treated samples, particularly TIGIT on CD8+ T cells and its receptor on cancer cells, and identified TIGIT as the major inhibitory checkpoint molecule of CD8+ T cells. Our results suggest that chemotherapy profoundly impacts the PDAC TME and may promote resistance to immunotherapy.

Recently, an unprecedented observation of polar order, thermochromic behavior, and exotic mesophases in new chiral, bent-shaped systems with a -CH3 moiety placed at the transverse position of the central core was reported. Herein, a homologous series of compounds with even-numbered carbon chains from n=4 to 18 were synthesized, in which -Cl was substituted for -CH3 at the kink position and a drastic modification in the phase structure of the bent-shaped molecule was observed. An unusual stabilization of the cubic blue phase (BP) over a wide range of 16.4 °C has been witnessed. Two homologues in this series (1-12 and 1-14) exhibit an interesting phase sequence consisting of BPI/II, chiral nematic, twist grain boundary, smectic A, and smectic X (SmX) phases. The higher homologues (1-16 and 1-18) stabilize the SmX phase enantiotropically over the entire temperature range. Crystal structure analysis confirmed the bent molecular architecture, with a bent angle of 148°, and revealed the presence of two different molecular conformations in an asymmetric unit of compound 1-4. A DFT study corroborated that the -Cl moiety at the central core of the molecule led to an increase in the dipole moment along the transverse direction, which, in turn, facilitated the unusual stabilization of frustrated structures. Crystal polymorphism has been evidenced in three homologues (1-10, 1-12, and 1-14) of the series. On the application of mechanical pressure through grinding, compound 1-10 transformed from a bright yellow crystalline solid to a dark orange-green amorphous solid, which reversed upon dropwise addition of dichloromethane, indicating reversible mechanochromism in this class of compounds. In addition, excellent thermochromic behavior has been observed for compound 1-10 with a controlled temperature-color combination.

The electroviscous effect deals with the change in the viscosity of fluids due to an external electric field. Here, we report experimental studies on the electroviscous effects in a ferroelectric nematic liquid crystal. It was synthesised accomplishing a new synthetic route which provides higher yield than conventional one. We measure electric field-dependent viscosity under a steady shear at different temperatures. In the low field range, the increase in viscosity ($\Delta\eta=\eta(E)-\eta_0$) is proportional to $E^2$ and the corresponding viscoelectric coefficient ($f\approx10^{-9}$m\textsuperscript{2}/V\textsuperscript{2}) of the ferroelectric nematic is 2 orders of magnitude larger than the apolar nematic liquid crystals and largest ever measured for a fluid. The apparent viscosity measured under a high electric field shows a power-law divergence $\eta\sim(T-T_c)^{-0.7\pm0.05}$, followed by nearly an order of magnitude drop below the N-N\textsubscript{F} phase transition. Experimental results within the dynamical scaling approximation demonstrate rapid growth of polar domains under a strong electric field as the N-N\textsubscript{F} phase transition is approached. The gigantic electroviscous effects demonstrated here are important for emerging applications and understanding striking electrohydromechanical effects in ferroelectric nematic liquid crystals., Comment: 5 figures

Nontrivial shape of colloidal particles create complex elastic distortions and topological defects in liquid crystals and play a key role in governing their electrophoretic propulsion through the medium. Here, we report experimental results on defects and electrophoretic transport of anisometric (snowman-shaped) dielectric particles subjected to an alternating electric field perpendicular to the director in a nematic liquid crystal. We demonstrate that the shape asymmetry gives rise to defect-polymorphism by nucleating point or ring defects at multiple locations on the particle and controls the direction as well as the magnitude of the electrophoretic propulsion. Our findings unveil a novel degree of freedom in translocating microparticles in liquid crystals for applications in microfluidics, controlled transport and assembly., Comment: 12 pages, 4 figures

Two-dimensional liquid crystal (LC) models of interacting V-shaped bent-core molecules with two rigid rodlike identical segments connected at a fixed angle (θ=112^{∘}) are investigated. The model assigns equal biquadratic tensor coupling among constituents of the interacting neighboring molecules on a square lattice, allowing for reorientations in three dimensions (d=2, n=3). We find evidence of two temperature-driven topological transitions mediated by point disclinations associated with the three ordering directors, condensing the LC medium successively into uniaxial and biaxial phases. With Monte Carlo simulations, temperature dependencies of the system energy, specific heat, orientational order parameters, topological order parameters, and densities of unbound topological defects of the different ordering directors are computed. The high-temperature transition results in topological ordering of disclinations of the primary director, imparting uniaxial symmetry to the phase. The low-temperature transition precipitates simultaneous topological ordering of defects of the remaining directors, resulting in biaxial symmetry. The correlation functions, quantifying spatial variations of the orientational correlations of the molecular axes show exponential decays in the high-temperature (disordered) phase, and power-law decays in the low-temperature (biaxial) phase. Differing temperature dependencies of the topological parameters point to a significant degree of cross coupling among the uniaxial and biaxial tensors of interacting molecules. This simplified Hamiltonian leaves θ as the only free model parameter, and the system traces a θ-dependent trajectory in a plane of the phenomenological parameter space.

We study the flow behaviour of a twist-bend nematic $(N_{TB})$ liquid crystal. It shows three distinct shear stress ($\sigma$) responses in a certain range of temperatures and shear rates ($\dot{\gamma}$). In Region-I, $\sigma\sim\sqrt{\dot{\gamma}}$, in region-II, the stress shows a plateau, characterised by a power law $\sigma\sim{\dot{\gamma}}^{\alpha}$, where $\alpha\sim0.1-0.4$ and in region-III, $\sigma\sim\dot{\gamma}$. With increasing shear rate, $\sigma$ changes continuously from region-I to II, whereas it changes discontinuously with a hysteresis from region-II to III. In the plateau (region-II), we observe a dynamic stress fluctuations, exhibiting regular, periodic and quasiperiodic oscillations under the application of steady shear. The observed spatiotemporal dynamics in our experiments are close to those were predicted theoretically in sheared nematogenic fluids.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) is a complex ecosystem that drives tumor progression. Improving our understanding of the PDAC TME and its role in response to therapy via in-depth single cell characterization will have broad clinical implications for biomarker development and therapeutic design. In this study, we performed single-cell RNA sequencing on freshly collected human PDAC samples of primary (n=16) or metastatic (n=11) origin, either before (n=20) or after (n=7) chemotherapy. We found a heterogeneous mixture of basal and classical Moffitt cancer cell subtypes in all samples, along with distinct cancer-associated fibroblast (CAF) and tumor-associated macrophage (TAM) subpopulations. We identified the major CAF subpopulations as inflammatory CAFs (iCAFs) and myofibroblastic CAFs (myCAFs); within these subpopulations were a very few cells expressing immunogenic features which have previously been associated with antigen presenting CAFs (apCAFs). Tumor-associated macrophages (TAMs) could be categorized into two major subpopulations, C1QC+ TAMs or SPP1+ TAMs, each with distinct functional characteristics. For example, phagocytosis-associated gene sets were enriched in C1QC+ TAMs, while angiogenesis-associated gene sets were enriched in SPP1+ TAMs. Comparison of naïve and chemotherapy treated primary PDAC samples revealed that classical and basal-like cancer cells exhibited similar transcriptional responses to chemotherapy; this contrasts with some previous reports which posited a shift towards a basal-like transcriptional program among treated samples. We further noted that treated samples evinced fewer ligand-receptor interactions, particularly between TIGIT on CD8+ T cells and its ligand on cancer cells. We also identified TIGIT, not PD1, as the major inhibitory checkpoint molecule of CD8+ T cells in the PDAC TME. Altogether, our results suggest that chemotherapy impacts the PDAC TME and may further reduce response to immunotherapy. Citation Format: Daniel Weissinger, Emily A. Kawaler, Gregor Werba, Ende Zhao, Despoina Kalfakakou, Surajit Dhara, Grace Oh, Xiaohong Jing, Nina Beri, Lauren Khanna, Tamas Gonda, Paul E. Oberstein, Cristina Hajdu, Cynthia Loomis, Adriana Heguy, Mara H. Sherman, Amanda W. Lund, Theodore H. Welling, Igor Dolgalev, Aristotelis Tsirigos, Diane M. Simeone. Single-cell sequencing elucidates the effects of chemotherapy on cancer cell heterogeneity and the tumor microenvironment of human pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr PR010.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy that harbors mutations in homologous recombination (HR) repair genes in up to 25% of cases. Defects in HR impart to tumor cells a specific vulnerability to poly-ADP ribose polymerase inhibitors and platinum-based chemotherapy. However, not all patients respond, and some who initially respond develop resistance and progress. Thus, new therapies that are effective against HR-deficient PDAC are needed. Here, we show that inactivation of the HR pathway in PDAC is associated with overexpression of polymerase theta (Polθ, or POLQ), a key enzyme that regulates the alternative non-homologous end-joining (alt-NHEJ) pathway of double-strand break (DSB) DNA repair. Using both human and murine HR-deficient PDAC models, we find that POLQ knockdown is synthetically lethal with mutations in HR genes (BRCA1, BRCA2, and PALB2) as well as the DNA damage repair gene ATM. Further, we present the first findings that POLQ knockdown enhances cytosolic micronucleus formation and activates cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling. In an in vivo murine model, POLQ inhibition also leads to STING-dependent recruitment of immune cells and enhanced CD8+ T cell infiltration in the BRCA2-deficient tumor microenvironment (TME). Through its role in the alt-NHEJ pathway, we thus find that POLQ is critical for DSB repair in HR-deficient PDAC, and its inhibition presents a novel synthetic lethal approach to suppress tumor growth while simultaneously stimulating an immune response in the PDAC TME. Citation Format: Grace Oh, Annie Wang, Lidong Wang, Jiufeng Li, Gregor Werba, Daniel Weissinger, Ende Zhao, Surajit Dhara, Rosmel Hernandez, Amanda Ackermann, Despoina Kalfakakou, Emily A. Kawaler, Talia Golan, Theodore H. Welling, Agnel Sfeir, Diane M. Simeone. Polymerase theta inhibition activates the cGAS-STING signaling pathway and elicits an immune response in homologous recombination-deficient pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B065.

We present a brief review on the effect of phase transitions on liquid crystal colloids. The paper focuses on the evolution of dipolar, quadrupolar and boojum colloids and the ensuing elastic disto...

Many bent-core nematic liquid crystals exhibit unusual physical properties due to the presence of smectic clusters, known as "cybotactic" clusters, in the nematic phase. Here, we investigate the effect of these clusters on the complex shear modulus (G*(ω)) of two asymmetric bent-core liquid crystals using a microrheological technique. The compound with a shorter hydrocarbon chain (8OCH3) exhibits only a nematic (N) phase whereas the compound with a longer chain (16OCH3) exhibits both nematic (N) and smectic-A (SmA) phases. The rheological results are correlated with the measurements of curvature elastic constants. Our results show that the directional shear modulus of 16OCH3, just above the SmA to N phase transition temperature, is strikingly different than that of 8OCH3, owing to the smectic clusters. An approximate size of the clusters is estimated using a simple model. Therefore, microrheological studies on bent-core nematic liquid crystals are very useful in extracting information about underlying smectic clusters.

We investigated tumor-cell-intrinsic chromatin accessibility patterns of pancreatic ductal adenocarcinoma (PDAC) by ATAC-seq on EpCAM+ PDAC malignant epithelial cells, sorted from 54 freshly resected human tumors, and discovered a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS) < 1 year and patients with DFS > 1 year. Analyzing transcription factor (TF) binding motifs within these loci, we identified two TFs (ZKSCAN1 and HNF1b) displaying differential nuclear localization between patients with short vs. long DFS. We further developed a novel chromatin accessibility microarray methodology termed ATAC-Array, an easy-to-use platform obviating the time and cost of next generation sequencing. Applying this novel methodology to the original ATAC-seq libraries as well as independent libraries generated from patient-derived organoids, we validated ATAC-array technology in both the original ATAC-Seq cohort as well as in an independent validation cohort. We conclude that PDAC prognosis can be predicted by ATAC-array, which represents a novel, low-cost, clinically feasible technology for assessing chromatin accessibility profiles.

We study the pair interaction of charged silica microrods in chiral nematic liquid crystals and show that the microrods with homeotropic surface anchoring form a bound state due to the competing effect of electrostatic (Coulomb) and elastic interactions. The robustness of the bound state is demonstrated by applying external electrical and mechanical forces that perturbs their equilibrium position as well as orientation. In the bound state we have measured the correlated thermal fluctuations of the position, using two-particle cross-correlation spectroscopy that uncovers their hydrodynamic interaction. These findings reveal unexplored aspects of liquid-crystal dispersions which are important for understanding the assembly and dynamics of nano and microparticles in chiral nematic liquid crystals., Comment: 9 pages, 10 figures

We study electrophoretic mobility of metal-dielectric Janus particles with dipolar director profile in two nematic liquid crystals (LCs) having same (positive) conductivity anisotropy and opposite dielectric anisotropy. The applied ac electric field is parallel and perpendicular to the director for the positive and negative dielectric anisotropy LCs, respectively. The velocity of the Janus particles in both LCs is significantly higher than that of the non-Janus particles. We map the electroosmotic flow fields surrounding the particles using microparticle image velocimetry ($\mu$-PIV) and show that the flows on the metal hemisphere is stronger than that on the dielectric hemisphere and the pumping of LC along the direction of motion of the Janus particles is more than that of the non-Janus particles. For a given liquid crystal, particles with asymmetric surface properties is useful for enhancing their electrophoretic mobility and activity., Comment: 6 pages, 6 figures

Unlike other malignancies, therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. Here we report tumor-cell-intrinsic chromatin accessibility patterns of treatment-naïve surgically resected PDAC tumors that were subsequently treated with (Gem)/Abraxane adjuvant chemotherapy. By ATAC-seq analyses of EpCAM+ PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we show here the discovery of a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS) 1 year. Analyzing transcription factor (TF) binding motifs within these loci, we identify two TFs (ZKSCAN1 and HNF1b) displaying differential nuclear localization between patients with short vs. long DFS. We further develop a chromatin accessibility microarray methodology termed “ATAC-array”, an easy-to-use platform obviating the time and cost of next generation sequencing. Applying this methodology to the original ATAC-seq libraries as well as independent libraries generated from patient-derived organoids, we validate ATAC-array technology in both the original ATAC-seq cohort as well as in an independent validation cohort. We conclude that PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles., ATAC-seq allows for the investigation of chromatin accessibility, a feature which can have important implications for gene regulation. Here the authors present ATAC-array to assess accessibility in human tumours and based on this predict disease prognosis.

Janus particles are special types of nanoparticles or microparticles possessing at least two surfaces with distinct physical or chemical properties. The most-studied Janus particles are metal-dielectric particles, in which half the surface of the dielectric particles is coated with a very thin layer of a metal. The external electric field induces a dipole moment, and consequently the particles exhibit self-assembled dynamic structures in concentrated aqueous suspensions. Here we study metal-dielectric Janus particles in a nematic liquid crystal under an ac electric field and demonstrate a method for measuring the effective induced dipole moments of the particles through competition between elastic and electrostatic (Coulomb) forces of the two particles. The calculated polarizability of the particles based on a simple model agrees well with the effective polarizability measured in the experiments. Our findings have important bearing on functional materials based on metal-dielectric Janus particles dispersed in an anisotropic medium.

We report experimental studies on the self-assembly of silica microspheres and Laponite nanoplatelets (NPs) in evaporating sessile droplets and in thin films, respectively. A ring-like stain of the silica microspheres with positional order is observed after the evaporation of sessile droplets due to the coffee-ring effect. This effect is suppressed in the binary mixtures of silica microspheres and Laponite NPs. A depletion zone has been observed in the mixtures during the sessile droplet evaporation, the width of which can be tuned by varying the compositions. We demonstrate a simple method for preparing core–shell particles by evaporating thin films of binary mixtures in which the Laponite NPs self-assemble to form a crystalline shell on the amorphous silica microspheres. We present a possible orientation of the Laponite NPs in the shell.

We create controllable active particles in the form of metal-dielectric Janus colloids which acquire motility through a nematic liquid crystal film by transducing the energy of an imposed perpendicular AC electric field. We achieve complete command over trajectories by varying field amplitude and frequency, piloting the colloids at will in the plane spanned by the axes of the particle and the nematic. The underlying mechanism exploits the sensitivity of electro-osmotic flow to the asymmetries of the particle surface and the liquid-crystal defect structure. We present a calculation of the dipolar force density produced by the interplay of the electric field with director anchoring and the contrasting electrostatic boundary conditions on the two hemispheres, that accounts for the dielectric-forward (metal-forward) motion of the colloids due to induced puller (pusher) force dipoles. These findings open unexplored directions for the use of colloids and liquid crystals in controlled transport, assembly and collective dynamics., Comment: 11 pages, 9 figures

In the present study, an ionic liquid (IL), known as green solvent, 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM-BF4) with four carbons in the hydrophobic chain (C-4) has been used a...

Colloidal particles in nematic liquid crystals create elastic distortion and experience long-range forces. The symmetry of elastic distortion and consequently the complexity of interaction strongly depends largely on the liquid crystal anchoring, topology and shape of the particles. Here, we introduce a new nematic colloidal system made of peanut-shaped hematite particles. We report experimental studies on spontaneous orientation, mutual interaction, laser assisted self-assembly and the effect of external magnetic fields on the colloids. Majority of the colloids spontaneously orient either parallel or perpendicular to the nematic director. The colloids that are oriented perpendicularly exhibit two types of textures due to the out of plane tilting, which is corroborated by the Landau-de Gennes Q-tensor modelling. The transverse magnetic moment of the peanut-shaped colloids is estimated by using a simple analysis based on the competing effects of magnetic and elastic torques.

In recent years, investigation on the non-display applications of liquid crystals has increased considerably. One of the emerging applications is whispering gallery mode (WGM) lasing. Here, we report experimental studies on the morphology and WGM lasing in nematic (N), smectic-A (SmA) and smectic-C (SmC) microdroplets dispersed in a highly transparent and low refractive index perfluopolymer. The mesomorphic microdroplets, obtained by varying the temperature, exhibit radial director configuration. The SmA microdroplets are found to be highly stable and robust against mechanical stress compared to the N and SmC microdroplets. We study lasing properties such as intensity, threshold pump energy and linewidth, and show that overall the SmA microdroplets are superior to the N and SmC microdroplets. The experimental results are discussed based on the orientation of the dye molecules, director fluctuations and tilting at the interface.

Liquid crystal (LC) based tuneable optical microresonators are potential for being used as crucial components in photonic devices. In this article, we report experimental studies on LC micro-drople...

Thiol terminated pentaalkynylbenzene (PA) units were synthesized for coating on gold nanoparticles (GNPs) in order to obtain materials with a combination of the properties of GNPs and discotic nematogens. The PA unit with the longest terminal alkyl spacer was found to exhibit a discotic nematic (ND) mesophase at room temperature which was preserved even after coating them on GNPs. The effect of GNPs on the orientational order parameter and the dielectric properties of the ND mesophase have been investigated from various physical measurements. To the best of our knowledge, this is the first example of a room-temperature discotic nematic liquid crystal made of gold nanoparticles.

In a sharp contrast to the response of silica particles we show that the metal-dielectric Janus particles with boojum defects in a nematic liquid crystal are self-propelled under the action of an electric field applied perpendicular to the director. The particles can be transported along any direction in the plane of the sample by selecting the appropriate orientation of the Janus vector with respect to the director. The direction of motion of the particles is controllable by varying the field amplitude and frequency. The command demonstrated on the motility of the particles is promising for tunable transport and microrobotic applications., Comment: 6 pages, 6 figures

The design and synthesis of three room-temperature discotic nematic (ND ) liquid crystals (LCs) is presented. The LC consists of an azobenzene core attached to which are four pentaalkynylbenzene (PA) units through flexible alkyl spacers. The presence of a short azo linking group provides more disorder in the system, thereby reducing the packing efficiency among the PA units and resulting into the formation of a room-temperature ND phase over a wide temperature range. Dielectric constant and birefringence studies were performed to gain further insights into the physical properties of the mesophase.

In twist-bend nematic (N\textsubscript{TB}) liquid crystals (LCs), the mean molecular orientation exhibits heliconical structure with nanoscale periodicity. On the mesoscopic scale, N\textsubscript{TB} resembles layered systems (like smectics), where the helical pitch is equivalent to "pseudo-layers" without a true mass density wave. We study rheological properties of a N\textsubscript{TB} phase and compare the results with those of an usual SmA phase. Analysing the shear response and adapting a simplified physical model for rheology of defect mediated lamellar systems we measure the pseudo-layer compression elastic constant $B_{eff}$ of N\textsubscript{TB} phase from the measurements of dynamic modulus $G^{*}(\omega)$. We find that $B_{eff}$ of the N\textsubscript{TB} phase is in the range of $10^{3}-10^{6}$ Pa and it follows a temperature dependence, $B_{eff}\sim (T_{TB}-T)^{2}$ as predicted by the recent coarse-grained elastic theory. Our results show that the structural rheology of N\textsubscript{TB} is strikingly similar to that of the usual smectic LCs although the temperature dependence of $B_{eff}$ is much faster than smectic LCs as predicted by the coarse-grained models., Comment: 6 pages, 6 figures

Aqueous suspensions of thermo responsive poly (N-isopropyl acrylamide) (PNIPAM) microgel particles exhibit volume phase transition (VPT) around 34°C. PNIPAM microgel spheres are known to be core-shell type having a dense core and a fuzzy shell of dangling polymer chains. Recently (Joshi and Tata Colloid and Polymer Sci. 295, 1671 (2017)) it was shown that under dense conditions i.e. volume fraction, ϕ > 0.64 PNIPAM microgel suspensions exhibit glassy state and undergo two step yielding upon application of shear. Two-step yielding is observed only in colloidal systems with attractive interactions. Observation of two-step yielding is unusual in a PNIPAM microgel glasses as PNIPAM microgel particles are known to be repulsive soft-spheres. Tata and Joshi argued that two-step yielding in dense PNIPAM microgel occur due to the breaking of entanglements of dangling polymer chains between shells of microgels and breaking of the near neighbor cages, respectively. Motivated by these studies and to verify entanglements have really a role in yielding, we synthesized two types of PNIPAM microgel spheres one having only a homogeneous core (referred to as HC) and the other with usual core-shell type (referred to as CS ). We report here the results obtained by performing non-linear rheological measurements on dense suspensions of HC and CS type PNIPAM microgel spheres. We observed two steps yielding in dense CS PNIPAM microgels suspension in its glassy state, but not with HC-PNIPAM spheres. Apart from the above observation, we report here the detailed non-linear rheological study in dense colloidal glasses of HC and CS type PNIPAM microgel particles.

A new approach is reported for the design of a room-temperature discotic nematic (ND) liquid crystal (LC) dimer consisting of a triphenylene and a pentaalkynylbenzene unit linked via flexible alkyl spacers. The formation of the ND phase is realized most likely through folding of the dimeric molecule that prevent stacking between the triphenylene units, as suggested by modelling in the mesophase derived from X-ray scattering results and high-level DFT calculations.

SummaryExtensive transcriptional and ontogenetic diversity exists among normal tissue-resident macrophages, with unique transcriptional profiles endowing the cells with tissue-specific functions. However, it is unknown whether the origins of different macrophage populations affect their roles in malignancy. Given potential artifacts associated with irradiation-based lineage tracing, it remains unclear if bone-marrow-derived macrophages (BMDMs) are present in tumors of the brain, a tissue with no homeostatic involvement of BMDMs. Here, we employed multiple models of murine brain malignancy and genetic lineage tracing to demonstrate that BMDMs are abundant in primary and metastatic brain tumors. Our data indicate that distinct transcriptional networks in brain-resident microglia and recruited BMDMs are associated with tumor-mediated education yet are also influenced by chromatin landscapes established before tumor initiation. Furthermore, we demonstrate that microglia specifically repress Itga4 (CD49D), enabling its utility as a discriminatory marker between microglia and BMDMs in primary and metastatic disease in mouse and human.