74 research outputs found
n-atic Order and Continuous Shape Changes of Deformable Surfaces of Genus Zero
We consider in mean-field theory the continuous development below a
second-order phase transition of -atic tangent plane order on a deformable
surface of genus zero with order parameter . Tangent plane order expels Gaussian curvature. In addition, the total
vorticity of orientational order on a surface of genus zero is two. Thus, the
ordered phase of an -atic on such a surface will have vortices of
strength , zeros in its order parameter, and a nonspherical
equilibrium shape. Our calculations are based on a phenomenological model with
a gauge-like coupling between and curvature, and our analysis follows
closely the Abrikosov treatment of a type II superconductor just below
.Comment: REVTEX, 12 page
Coupling between Smectic and Twist Modes in Polymer Intercalated Smectics
We analyse the elastic energy of an intercalated smectic where
orientationally ordered polymers with an average orientation varying from layer
to layer are intercalated between smectic planes. The lowest order terms in the
coupling between polymer director and smectic layer curvature are added to the
smectic elastic energy. Integration over the smectic degrees of freedom leaves
an effective polymer twist energy that has to be included into the total
polymer elastic energy leading to a fluctuational renormalization of the
intercalated polymer twist modulus. If the polymers are chiral this in its turn
leads to a renormalization of the cholesteric pitch.Comment: 8 pages, 1 fig in ps available from [email protected] Replaced
version also contains title and abstract in the main tex
Statistical Mechanics of Vacancy and Interstitial Strings in Hexagonal Columnar Crystals
Columnar crystals contain defects in the form of vacancy/interstitial loops
or strings of vacancies and interstitials bounded by column ``heads'' and
``tails''. These defect strings are oriented by the columnar lattice and can
change size and shape by movement of the ends and forming kinks along the
length. Hence an analysis in terms of directed living polymers is appropriate
to study their size and shape distribution, volume fraction, etc. If the
entropy of transverse fluctuations overcomes the string line tension in the
crystalline phase, a string proliferation transition occurs, leading to a
supersolid phase. We estimate the wandering entropy and examine the behaviour
in the transition regime. We also calculate numerically the line tension of
various species of vacancies and interstitials in a triangular lattice for
power-law potentials as well as for a modified Bessel function interaction
between columns as occurs in the case of flux lines in type-II superconductors
or long polyelectrolytes in an ionic solution. We find that the centered
interstitial is the lowest energy defect for a very wide range of interactions;
the symmetric vacancy is preferred only for extremely short interaction ranges.Comment: 22 pages (revtex), 15 figures (encapsulated postscript
Defects in Chiral Columnar Phases: Tilt Grain Boundaries and Iterated Moire Maps
Biomolecules are often very long with a definite chirality. DNA, xanthan and
poly-gamma-benzyl-glutamate (PBLG) can all form columnar crystalline phases.
The chirality, however, competes with the tendency for crystalline order. For
chiral polymers, there are two sorts of chirality: the first describes the
usual cholesteric-like twist of the local director around a pitch axis, while
the second favors the rotation of the local bond-orientational order and leads
to a braiding of the polymers along an average direction. In the former case
chirality can be manifested in a tilt grain boundary phase (TGB) analogous to
the Renn-Lubensky phase of smectic-A liquid crystals. In the latter case we are
led to a new "moire" state with twisted bond order. In the moire state polymers
are simultaneously entangled, crystalline, and aligned, on average, in a common
direction. In the moire state polymers are simultaneously entangled,
crystalline, and aligned, on average, in a common direction. In this case the
polymer trajectories in the plane perpendicular to their average direction are
described by iterated moire maps of remarkable complexity, reminiscent of
dynamical systems.Comment: plain TeX, (33 pages), 17 figures, some uufiled and included, the
remaining available at ftp://ftp.sns.ias.edu/pub/kamien/ or by request to
[email protected]
Identification and characterization of the maize arogenate dehydrogenase gene family
In plants, the amino acids tyrosine and phenylalanine are synthesized from arogenate by arogenate dehydrogenase and arogenate dehydratase, respectively, with the relative flux to each being tightly controlled. Here the characterization of a maize opaque endosperm mutant (mto140), which also shows retarded vegetative growth, is described The opaque phenotype co-segregates with a Mutator transposon insertion in an arogenate dehydrogenase gene (zmAroDH-1) and this led to the characterization of the four-member family of maize arogenate dehydrogenase genes (zmAroDH-1–zmAroDH-4) which share highly similar sequences. A Mutator insertion at an equivalent position in AroDH-3, the most closely related family member to AroDH-1, is also associated with opaque endosperm and stunted vegetative growth phenotypes. Overlapping but differential expression patterns as well as subtle mutant effects on the accumulation of tyrosine and phenylalanine in endosperm, embryo, and leaf tissues suggest that the functional redundancy of this gene family provides metabolic plasticity for the synthesis of these important amino acids. mto140/arodh-1 seeds shows a general reduction in zein storage protein accumulation and an elevated lysine phenotype typical of other opaque endosperm mutants, but it is distinct because it does not result from quantitative or qualitative defects in the accumulation of specific zeins but rather from a disruption in amino acid biosynthesis
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Open-label extension of a phase 2 trial of risankizumab in patients with moderate-to-severe Crohn's disease
Background: Risankizumab, an anti-interleukin-23 antibody, was superior to placebo in achieving clinical and endoscopic remission at week 12 in a randomised, phase 2 induction study in patients with moderately to severely active Crohn’s disease. The efficacy and safety of extended intravenous induction and/or subcutaneous maintenance therapy with risankizumab was assessed.
Methods: Following 12-week, double-blind, randomised, induction treatment comparing 200 mg or 600 mg intravenous risankizumab to placebo every 4 weeks, patients without deep remission, defined as clinical (Crohn’s Disease Activity Index <150) and endoscopic remission (Crohn’s Disease Endoscopic Index of Severity [CDEIS] ≤4 [≤2 for patients with isolated ileitis]), received open-label 600 mg intravenous risankizumab (every 4 weeks) and patients in deep remission underwent washout until week 26 (Period 2). At week 26, patients in clinical remission received maintenance treatment (Period 3) with 180 mg subcutaneous risankizumab (every 8 weeks). Efficacy endpoints included clinical and endoscopic response and remission at weeks 26 (Period 2) and 52 (Period 3) respectively; safety was assessed through both periods. Study registration: ClinicalTrials.gov, NCT02031276.
Findings: In Period 2, 101 patients were treated with 600 mg risankizumab resulting in an increase in clinical remission rates at week 26 versus week 12 for all original designated treatment groups: 55% versus 18%, 59% versus 21%, and 47% versus 26% for placebo, 200, and 600 mg risankizumab, respectively. Of the 62 patients receiving maintenance treatment, 54 completed treatment. At week 52, clinical remission was maintained by 71% of patients; endoscopic remission and response (>50% CDEIS reduction from baseline) was achieved by 35% and 55% of patients, respectively, and 29% of patients achieved deep remission. Risankizumab was well tolerated with no new safety signals.
Interpretation: Extended induction treatment with open-label intravenous risankizumab was effective in increasing clinical response and remission rates at week 26. Open-label subcutaneous risankizumab maintained remission till week 52 in most patients who were in clinical remission at week 26. Selective blockade of interleukin-23 warrants further evaluation as treatment for Crohn’s disease.Boehringer Ingelhei
Formation and annihilation of nanocavities during keV ion irradiation of Ge
Nanocavities in Ge(111) created by 5 keV Xe ion irradiation are characterized
by ex situ transmission electron microscopy and Rutherford backscattering
spectrometry. Nanocavities nucleate near the surface and then undergo thermal
migration. Nanocavities with average diameter of 10 nm and areal density of 5.1
x 10-3 nm-2 are observed at 773 K, while nanocavities with average diameter of
2.9 nm and areal density of 3.1 x 10-3 nm-2 are observed at 673 K. The
estimated Xe gas pressure inside the nanocavities is 0.035 GPa at 773 K, much
smaller than the estimated equilibrium pressure 0.38 GPa. This result suggests
that the nanocavities grow beyond equilibrium size at 773 K. The nanocavities
are annihilated at the surface to form surface pits by the interaction of
displacement cascades of keV Xe ions with the nanocavities. These pits are
characterized by in situ scanning tunneling microscopy. Pits are created on
Ge(111) and Ge(001) at temperatures ~ 523-578 K by keV Xe ions even when less
than a bilayer (monolayer) of surface material is removed.Comment: 26 pages, 7 figures, to be published in Physical Review
Spherical surface models with directors
A triangulated spherical surface model is numerically studied, and it is
shown that the model undergoes phase transitions between the smooth phase and
the collapsed phase. The model is defined by using a director field, which is
assumed to have an interaction with a normal of the surface. The interaction
between the directors and the surface maintains the surface shape. The director
field is not defined within the two-dimensional differential geometry, and this
is in sharp contrast to the conventional surface models, where the surface
shape is maintained only by the curvature energies. We also show that the
interaction makes the Nambu-Goto model well-defined, where the bond potential
is given by the area of triangles; the Nambu-Goto model is well-known as an
ill-defined one even when the conventional two-dimensional bending energy is
included in the Hamiltonian.Comment: 18 pages, 13 figure
Dynamic probe selection for studying microbial transcriptome with high-density genomic tiling microarrays
<p>Abstract</p> <p>Background</p> <p>Current commercial high-density oligonucleotide microarrays can hold millions of probe spots on a single microscopic glass slide and are ideal for studying the transcriptome of microbial genomes using a tiling probe design. This paper describes a comprehensive computational pipeline implemented specifically for designing tiling probe sets to study microbial transcriptome profiles.</p> <p>Results</p> <p>The pipeline identifies every possible probe sequence from both forward and reverse-complement strands of all DNA sequences in the target genome including circular or linear chromosomes and plasmids. Final probe sequence lengths are adjusted based on the maximal oligonucleotide synthesis cycles and best isothermality allowed. Optimal probes are then selected in two stages - sequential and gap-filling. In the sequential stage, probes are selected from sequence windows tiled alongside the genome. In the gap-filling stage, additional probes are selected from the largest gaps between adjacent probes that have already been selected, until a predefined number of probes is reached. Selection of the highest quality probe within each window and gap is based on five criteria: sequence uniqueness, probe self-annealing, melting temperature, oligonucleotide length, and probe position.</p> <p>Conclusions</p> <p>The probe selection pipeline evaluates global and local probe sequence properties and selects a set of probes dynamically and evenly distributed along the target genome. Unique to other similar methods, an exact number of non-redundant probes can be designed to utilize all the available probe spots on any chosen microarray platform. The pipeline can be applied to microbial genomes when designing high-density tiling arrays for comparative genomics, ChIP chip, gene expression and comprehensive transcriptome studies.</p
Susceptibility to chronic mucus hypersecretion, a genome wide association study
Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations.Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and metaanalysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (>= 20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP).Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25610(-6), OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3610 29) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture.Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.</p
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