Asymptotic Limits and Zeros of Chromatic Polynomials and Ground State Entropy of Potts Antiferromagnets

We study the asymptotic limiting function $W({G},q) = \lim_{n \to \infty}P(G,q)^{1/n}$, where $P(G,q)$ is the chromatic polynomial for a graph $G$ with $n$ vertices. We first discuss a subtlety in the definition of $W({G},q)$ resulting from the fact that at certain special points $q_s$, the following limits do not commute: $\lim_{n \to \infty} \lim_{q \to q_s} P(G,q)^{1/n} \ne \lim_{q \to q_s} \lim_{n \to \infty} P(G,q)^{1/n}$. We then present exact calculations of $W({G},q)$ and determine the corresponding analytic structure in the complex $q$ plane for a number of families of graphs ${G}$, including circuits, wheels, biwheels, bipyramids, and (cyclic and twisted) ladders. We study the zeros of the corresponding chromatic polynomials and prove a theorem that for certain families of graphs, all but a finite number of the zeros lie exactly on a unit circle, whose position depends on the family. Using the connection of $P(G,q)$ with the zero-temperature Potts antiferromagnet, we derive a theorem concerning the maximal finite real point of non-analyticity in $W({G},q)$, denoted $q_c$ and apply this theorem to deduce that $q_c(sq)=3$ and $q_c(hc) = (3+\sqrt{5})/2$ for the square and honeycomb lattices. Finally, numerical calculations of $W(hc,q)$ and $W(sq,q)$ are presented and compared with series expansions and bounds.Comment: 33 pages, Latex, 5 postscript figures, published version; includes further comments on large-q serie

Relativistic Effects in the Scalar Meson Dynamics

A separable potential formalism is used to describe the $\pi\pi$ and $K\overline{K}$ interactions in the scalar-isoscalar states in the energy range from the $\pi\pi$ threshold up to 1.4 GeV. Introduction of relativistic propagators into a system of Lippmann-Schwinger equations leads to a very good description of the data ($\chi^{2}=0.93$ per one degree of freedom). Three poles are found in this energy region: fo(500) ($M=506\pm 10$ MeV, $\Gamma=494\pm 5$ MeV), fo(975) ($M=973\pm 2$ MeV, $\Gamma=29\pm 2$ MeV) and fo(1400) ($M=1430\pm 5$ MeV, $\Gamma=145\pm 25$ MeV). The fo(975) state can be interpreted as a $K\overline{K}$ bound state. The fo(500) state may be associated with the often postulated very broad scalar resonance under the $K\overline{K}$ threshold (sometimes called $\sigma$ or $\epsilon$ meson). The scattering lengths in the $\pi\pi$ and $K\overline{K}$ channels have also been obtained. The relativistic approach provides qualitatively new results (e.g. the appearance of the fo(500)) in comparison with previously used nonrelativistic approach.Comment: 30 pages in LaTeX + 5 figures available on request. Preprint Orsay No IPNO/TH 93-3

The Sparrow Question: Social and Scientific Accord in Britain, 1850-1900.

During the latter-half of the nineteenth century, the utility of the house sparrow (Passer domesticus) to humankind was a contentious topic. In Britain, numerous actors from various backgrounds including natural history, acclimatisation, agriculture and economic ornithology converged on the bird, as contemporaries sought to calculate its economic cost and benefit to growers. Periodicals and newspapers provided an accessible and anonymous means of expression, through which the debate raged for over 50 years. By the end of the century, sparrows had been cast as detrimental to agriculture. Yet consensus was not achieved through new scientific methods, instruments, or changes in practice. This study instead argues that the rise and fall of scientific disciplines and movements paved the way for consensus on "the sparrow question." The decline of natural history and acclimatisation stifled a raging debate, while the rising science of economic ornithology sought to align itself with agricultural interests: the latter overwhelmingly hostile to sparrows

Expression of MAGE-C1/CT7 and MAGE-C2/CT10 Predicts Lymph Node Metastasis in Melanoma Patients

MAGE-C1/CT7 and MAGE-C2/CT10 are members of the large MAGE family of cancer-testis (CT) antigens. CT antigens are promising targets for immunotherapy in cancer because their expression is restricted to cancer and germ line cells and a proportion of cancer patients presents with immune responses against CT antigens, which clearly demonstrates their immunogenicity. This study investigates the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary and metastatic melanoma. Immunohistochemical staining of tissue microarrays that consisted of 59 primary malignant melanomas of the skin, 163 lymph node and distant melanoma metastases and 68 melanoma cell lines was performed. We found MAGE-C1/CT7 expression in 15 out of 50 (24%) primary melanomas and 15 out of 50 (24%) cell lines, whereas MAGE-C2/CT10 was detected in 17 out of 51 (33%) primary melanomas and 14 out of 68 (17%) cell lines. MAGE-C1/CT7 and MAGE-C2/CT10 were both detected in 40% of melanoma metastases. Patients with MAGE-C1/CT7 or MAGE-C2/CT10 positive primary melanoma had significantly more lymph node metastases (p = 0.005 and p<0.001, resp.). Prediction of lymph node metastasis by MAGE-C1/CT7 and MAGE-C2/CT10 was independent of tumor cell proliferation rate (Ki67 labeling index) in a multivariate analysis (p = 0.01). Our results suggest that the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary melanoma is a potent predictor of sentinel lymph node metastasis

Nanostructures, Technology, Research, and Applications

Contains reports on the nanostructures laboratory, eighteen research projects and a list of publications.Joint Services Electronics Program Grant DAAH04-95-1-0038Semiconductor Research Corporation Contract 95-LJ-550National Science Foundation Grant ECS 94-07078U.S. Army Research Office Grant DAAH04-95-1-0564Defense Advanced Research Projects Agency/Naval Air Systems Command Contract N00019-95-K-0131National Aeronautics and Space Administration Contract NAS8-38249National Aeronautics and Space Administration Grant NAGW-2003IBM Corporation Contract 1622U.S. Navy- Office of Naval Research Grant N00014-95-1-1297U.S. Army Research Office Grant DAAH04-94-G-0377U.S. Air Force - Office of Scientific Research Grant F-49-620-92-J-0064U.S. Air Force - Office of Scientific Research Grant F-49-620-95-1-031

Structure-Function Study of Mammalian Munc18-1 and C. elegans UNC-18 Implicates Domain 3b in the Regulation of Exocytosis

Munc18-1 is an essential synaptic protein functioning during multiple stages of the exocytotic process including vesicle recruitment, docking and fusion. These functions require a number of distinct syntaxin-dependent interactions; however, Munc18-1 also regulates vesicle fusion via syntaxin-independent interactions with other exocytotic proteins. Although the structural regions of the Munc18-1 protein involved in closed-conformation syntaxin binding have been thoroughly examined, regions of the protein involved in other interactions are poorly characterised. To investigate this we performed a random transposon mutagenesis, identifying domain 3b of Munc18-1 as a functionally important region of the protein. Transposon insertion in an exposed loop within this domain specifically disrupted Mint1 binding despite leaving affinity for closed conformation syntaxin and binding to the SNARE complex unaffected. The insertion mutation significantly reduced total amounts of exocytosis as measured by carbon fiber amperometry in chromaffin cells. Introduction of the equivalent mutation in UNC-18 in Caenorhabditis elegans also reduced neurotransmitter release as assessed by aldicarb sensitivity. Correlation between the two experimental methods for recording changes in the number of exocytotic events was verified using a previously identified gain of function Munc18-1 mutation E466K (increased exocytosis in chromaffin cells and aldicarb hypersensitivity of C. elegans). These data implicate a novel role for an exposed loop in domain 3b of Munc18-1 in transducing regulation of vesicle fusion independent of closed-conformation syntaxin binding

Pediatric T- and NK-cell lymphomas: new biologic insights and treatment strategies

T- and natural killer (NK)-cell lymphomas are challenging childhood neoplasms. These cancers have varying presentations, vast molecular heterogeneity, and several are quite unusual in the West, creating diagnostic challenges. Over 20 distinct T- and NK-cell neoplasms are recognized by the 2008 World Health Organization classification, demonstrating the diversity and potential complexity of these cases. In pediatric populations, selection of optimal therapy poses an additional quandary, as most of these malignancies have not been studied in large randomized clinical trials. Despite their rarity, exciting molecular discoveries are yielding insights into these clinicopathologic entities, improving the accuracy of our diagnoses of these cancers, and expanding our ability to effectively treat them, including the use of new targeted therapies. Here, we summarize this fascinating group of lymphomas, with particular attention to the three most common subtypes: T-lymphoblastic lymphoma, anaplastic large cell lymphoma, and peripheral T-cell lymphoma-not otherwise specified. We highlight recent findings regarding their molecular etiologies, new biologic markers, and cutting-edge therapeutic strategies applied to this intriguing class of neoplasms

Protein Phosphatase 2A Mediates Dormancy of Glioblastoma Multiforme-Derived Tumor Stem-Like Cells during Hypoxia

The hypoxic microenvironment of glioblastoma multiforme (GBM) is thought to increase resistance to cancer therapies. Recent evidence suggests that hypoxia induces protein phosphatase 2A (PP2A), a regulator of cell cycle and cell death. The effects of PP2A on GBM tumor cell proliferation and survival during hypoxic conditions have not been studied.Expression of PP2A subunits and HIF-α proteins was measured in 65 high-grade astrocytoma and 18 non-neoplastic surgical brain specimens by western blotting. PP2A activity was measured by an immunoprecipitation assay. For in vitro experiments, GBM-derived tumor stem cell-like cells (TSCs) were exposed to severe hypoxia produced by either CoCl₂ or 1% O₂. PP2A activity was inhibited either by okadaic acid or by shRNA depletion of the PP2A C subunit. Effects of PP2A activity on cell cycle progression and cell survival during hypoxic conditions were assessed using flow cytometry.In our patient cohort, PP2A activity was positively correlated with HIF-1∝ protein expression (P = 0.002). Patients with PP2A activity levels above 160 pMP had significantly worse survival compared to patients with levels below this threshold (P = 0.002). PP2A activity was an independent predictor of survival on multivariable analysis (P = 0.009). In our in vitro experiments, we confirmed that severe hypoxia induces PP2A activity in TSCs 6 hours after onset of exposure. PP2A activity mediated G1/S phase growth inhibition and reduced cellular ATP consumption in hypoxic TSCs. Conversely, inhibition of PP2A activity led to increased cell proliferation, exhaustion of intracellular ATP, and accelerated P53-independent cell death of hypoxic TSCs.Our results suggest that PP2A activity predicts poor survival in GBM. PP2A appears to reduce the metabolic demand of hypoxic TSCs and enhances tumor cell survival. Modulation of PP2A may be a potential target for cancer therapy

Functional Promoter Polymorphisms Govern Differential Expression of HMG-CoA Reductase Gene in Mouse Models of Essential Hypertension

3-Hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase gene (Hmgcr) is a susceptibility gene for essential hypertension. Sequencing of the Hmgcr locus in genetically hypertensive BPH (blood pressure high), genetically hypotensive BPL (blood pressure low) and genetically normotensive BPN (blood pressure normal) mice yielded a number of single nucleotide polymorphisms (SNPs). BPH/BPL/BPN Hmgcr promoter-luciferase reporter constructs were generated and transfected into liver HepG2, ovarian CHO, kidney HEK-293 and neuronal N2A cells for functional characterization of the promoter SNPs. The BPH-Hmgcr promoter showed significantly less activity than the BPL-Hmgcr promoter under basal as well as nicotine/cholesterol-treated conditions. This finding was consistent with lower endogenous Hmgcr expression in liver and lower plasma cholesterol in BPH mice. Transfection experiments using 5′-promoter deletion constructs (strategically made to assess the functional significance of each promoter SNP) and computational analysis predicted lower binding affinities of transcription factors c-Fos, n-Myc and Max with the BPH-promoter as compared to the BPL-promoter. Corroboratively, the BPH promoter-luciferase reporter construct co-transfected with expression plasmids of these transcription factors displayed less pronounced augmentation of luciferase activity than the BPL construct, particularly at lower amounts of transcription factor plasmids. Electrophoretic mobility shift assays also showed diminished interactions of the BPH promoter with HepG2 nuclear proteins. Taken together, this study provides mechanistic basis for the differential Hmgcr expression in these mouse models of human essential hypertension and have implications for better understanding the role of this gene in regulation of blood pressure

2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field