Knot contact homology

The conormal lift of a link $K$ in $\R^3$ is a Legendrian submanifold $\Lambda_K$ in the unit cotangent bundle $U^* \R^3$ of $\R^3$ with contact structure equal to the kernel of the Liouville form. Knot contact homology, a topological link invariant of $K$, is defined as the Legendrian homology of $\Lambda_K$, the homology of a differential graded algebra generated by Reeb chords whose differential counts holomorphic disks in the symplectization $\R \times U^*\R^3$ with Lagrangian boundary condition $\R \times \Lambda_K$. We perform an explicit and complete computation of the Legendrian homology of $\Lambda_K$ for arbitrary links $K$ in terms of a braid presentation of $K$, confirming a conjecture that this invariant agrees with a previously-defined combinatorial version of knot contact homology. The computation uses a double degeneration: the braid degenerates toward a multiple cover of the unknot which in turn degenerates to a point. Under the first degeneration, holomorphic disks converge to gradient flow trees with quantum corrections. The combined degenerations give rise to a new generalization of flow trees called multiscale flow trees. The theory of multiscale flow trees is the key tool in our computation and is already proving to be useful for other computations as well.Comment: v2: 120 pages, technical correction to choice of auxiliary angles in section 6.3.

Trastuzumab (Herceptin (R)): Monoclonal antibody in the treatment of HER2/neu-overexpressing breast cancer in the metastatic and (neo)adjuvant situation

Trastuzumab (Herceptin (R)) is a humanized monoclonal antibody that specifically targets HER2/neu (human epidermal growth factor receptor-2) breast cancer cells, which are overexpressed in about 25-30% of breast carcinomas. After phase I and II trials, several phase III studies of trastuzumab alone or in combination with various chemotherapies were conducted. Patients with HER2/neu overexpression levels of 3+ determined by immunohistochemical assay or gene amplification (fluorescence in situ hybridization) derive most clinical benefit from trastuzumab. Taking into consideration efficacy and side effect profile, the combination of trastuzumab and paclitaxel showed an improvement of all clinical parameters, including overall survival, for the first time in the history of palliative breast cancer therapy. The application of trastuzumab has meanwhile become an established part of systemic therapy of metastastic breast cancer, and excellent data of its application in the adjuvant setting now exist (NSABP-B31, NCCTG-N9831, HERA), with significantly better relapse-free survival in the treatment arms with trastuzumab. Ongoing trials investigate the role of trastuzumab in the neoadjuvant setting. Trastuzumab is generally well tolerated. Cardiotoxicity is the main concern, thus monitoring of cardiac function is recommended

Visible-to-telecom quantum frequency conversion of light from a single quantum emitter

Quantum frequency conversion (QFC), a nonlinear optical process in which the frequency of a quantum light field is altered while conserving its non-classical correlations, was first demonstrated 20 years ago. Meanwhile, it is considered an essential tool for the implementation of quantum repeaters since it allows for interfacing quantum memories with telecom-wavelength photons as quantum information carriers. Here we demonstrate efficient (>30%) QFC of visible single photons (711 nm) emitted by a quantum dot (QD) to a telecom wavelength (1,313 nm). Analysis of the first and second-order coherence before and after wavelength conversion clearly proves that important properties, such as the coherence time and photon antibunching, are fully conserved during the frequency translation process. Our findings underline the great potential of single photon sources on demand in combination with QFC as a promising technique for quantum repeater schemes.Comment: 11 pages, 4 figure

Filtrations on the knot contact homology of transverse knots

We construct a new invariant of transverse links in the standard contact structure on R^3. This invariant is a doubly filtered version of the knot contact homology differential graded algebra (DGA) of the link. Here the knot contact homology of a link in R^3 is the Legendrian contact homology DGA of its conormal lift into the unit cotangent bundle S^*R^3 of R^3, and the filtrations are constructed by counting intersections of the holomorphic disks of the DGA differential with two conormal lifts of the contact structure. We also present a combinatorial formula for the filtered DGA in terms of braid representatives of transverse links and apply it to show that the new invariant is independent of previously known invariants of transverse links.Comment: 23 pages, v2: minor corrections suggested by refere

Fruit shape diversity in the Brassicaceae is generated by varying patterns of anisotropy

Fruits exhibit a vast array of different 3D shapes, from simple spheres and cylinders to more complex curved forms; however, the mechanism by which growth is oriented and coordinated to generate this diversity of forms is unclear. Here, we compare the growth patterns and orientations for two very different fruit shapes in the Brassicaceae: the heart-shaped Capsella rubella silicle and the near-cylindrical Arabidopsis thaliana silique. We show, through a combination of clonal and morphological analyses, that the different shapes involve different patterns of anisotropic growth during three phases. These experimental data can be accounted for by a tissue-level model in which specified growth rates vary in space and time and are oriented by a proximodistal polarity field. The resulting tissue conflicts lead to deformation of the tissue as it grows. The model allows us to identify tissue-specific and temporally specific activities required to obtain the individual shapes. One such activity may be provided by the valve-identity gene FRUITFULL, which we show through comparative mutant analysis to modulate fruit shape during post-fertilisation growth of both species. Simple modulations of the model presented here can also broadly account for the variety of shapes in other Brassicaceae species, thus providing a simplified framework for fruit development and shape diversity

Genome-wide analysis of PAPS1-dependent polyadenylation identifies novel roles for functionally specialized poly(A) polymerases in Arabidopsis thaliana

The poly(A) tail at 3’ ends of eukaryotic mRNAs promotes their nuclear export, stability and translational efficiency, and changes in its length can strongly impact gene expression. The Arabidopsis thaliana genome encodes three canonical nuclear poly(A) polymerases,PAPS1, PAPS2 and PAPS4. As shown by their different mutant phenotypes, these three isoforms are functionally specialized, with PAPS1 modifying organ growth and suppressing a constitutive immune response. However, the molecular basis of this specialization is largely unknown. Here, we have estimated poly(A)-tail lengths on a transcriptome-wide scale in wild-type and paps1 mutants. This identified categories of genes as particularly strongly affected in paps1 mutants, including genes encoding ribosomal proteins, cell-division factors and major carbohydrate-metabolic proteins. We experimentally verified two novel functions of PAPS1 in ribosome biogenesis and redox homoeostasis that were predicted based on the analysis of poly(A)-tail length changes in paps1 mutants. When overlaying the PAPS1-dependent effects observed here with coexpression analysis based on independent microarray data, the two clusters of transcripts that are most closely coexpressed with PAPS1 show the strongest change in poly(A)-tail length and transcript abundance in paps1 mutants in our analysis. This suggests that their coexpression reflects at least partly the preferential polyadenylation of these transcripts by PAPS1 versus the other two poly(A)-polymerase isoforms. Thus, transcriptome-wide analysis of poly(A)-tail lengths identifies novel biological functions and likely target transcripts for polyadenylation by PAPS1. Data integration with large-scale co-expression data suggests that changes in the relative activities of the isoforms are used as an endogenous mechanism to co-ordinately modulate plant gene expression

Expression of the central growth regulator BIG BROTHER is regulated by multiple cis-elements

<p>Abstract</p> <p>Background</p> <p>Much of the organismal variation we observe in nature is due to differences in organ size. The observation that even closely related species can show large, stably inherited differences in organ size indicates a strong genetic component to the control of organ size. Despite recent progress in identifying factors controlling organ growth in plants, our overall understanding of this process remains limited, partly because the individual factors have not yet been connected into larger regulatory pathways or networks. To begin addressing this aim, we have studied the upstream regulation of expression of <it>BIG BROTHER </it>(<it>BB</it>), a central growth-control gene in <it>Arabidopsis thaliana </it>that prevents overgrowth of organs. Final organ size and <it>BB </it>expression levels are tightly correlated, implying the need for precise control of its expression. <it>BB </it>expression mirrors proliferative activity, yet the gene functions to limit proliferation, suggesting that it acts in an incoherent feedforward loop downstream of growth activators to prevent over-proliferation.</p> <p>Results</p> <p>To investigate the upstream regulation of <it>BB </it>we combined a promoter deletion analysis with a phylogenetic footprinting approach. We were able to narrow down important, highly conserved, <it>cis</it>-regulatory elements within the <it>BB </it>promoter. Promoter sequences of other Brassicaceae species were able to partially complement the <it>A. thaliana bb-1 </it>mutant, suggesting that at least within the Brassicaceae family the regulatory pathways are conserved.</p> <p>Conclusions</p> <p>This work underlines the complexity involved in precise quantitative control of gene expression and lays the foundation for identifying important upstream regulators that determine <it>BB </it>expression levels and thus final organ size.</p

Effect of sedimentary heterogeneities in the sealing formation on predictive analysis of geological CO₂ storage

Numerical models of geologic carbon sequestration (GCS) in saline aquifers use multiphase fluid flow-characteristic curves (relative permeability and capillary pressure) to represent the interactions of the non-wetting CO2 and the wetting brine. Relative permeability data for many sedimentary formations is very scarce, resulting in the utilisation of mathematical correlations to generate the fluid flow characteristics in these formations. The flow models are essential for the prediction of CO2 storage capacity and trapping mechanisms in the geological media. The observation of pressure dissipation across the storage and sealing formations is relevant for storage capacity and geomechanical analysis during CO2 injection. This paper evaluates the relevance of representing relative permeability variations in the sealing formation when modelling geological CO2 sequestration processes. Here we concentrate on gradational changes in the lower part of the caprock, particularly how they affect pressure evolution within the entire sealing formation when duly represented by relative permeability functions. The results demonstrate the importance of accounting for pore size variations in the mathematical model adopted to generate the characteristic curves for GCS analysis. Gradational changes at the base of the caprock influence the magnitude of pressure that propagates vertically into the caprock from the aquifer, especially at the critical zone (i.e. the region overlying the CO2 plume accumulating at the reservoir-seal interface). A higher degree of overpressure and CO2 storage capacity was observed at the base of caprocks that showed gradation. These results illustrate the need to obtain reliable relative permeability functions for GCS, beyond just permeability and porosity data. The study provides a formative principle for geomechanical simulations that study the possibility of pressure-induced caprock failure during CO2 sequestration

Para-fluorination of anilides using electrochemically generated hypervalent iodoarenes

The para-selective fluorination reaction of anilides using electrochemically generated hypervalent ArIF2 is reported, with Et3N ⋅ 5HF serving as fluoride source and as supporting electrolyte. This electrochemical reaction is characterized by a simple set-up, easy scalability and affords a broad variety of fluorinated anilides from easily accessible anilides in good yields up to 86 %

The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: CTCF is a highly conserved and essential zinc finger protein expressed in virtually all cell types. In conjunction with cohesin, it organizes chromatin into loops, thereby regulating gene expression and epigenetic events. The function of CTCFL or BORIS, the testis-specific paralog of CTCF, is less clear. RESULTS: Using immunohistochemistry on testis sections and fluorescence-based microscopy on intact live seminiferous tubules, we show that CTCFL is only transiently present during spermatogenesis, prior to the onset of meiosis, when the protein co-localizes in nuclei with ubiquitously expressed CTCF. CTCFL distribution overlaps completely with that of Stra8, a retinoic acid-inducible protein essential for the propagation of meiosis. We find that absence of CTCFL in mice causes sub-fertility because of a partially penetrant testicular atrophy. CTCFL deficiency affects the expression of a number of testis-specific genes, including Gal3st1 and Prss50. Combined, these data indicate that CTCFL has a unique role in spermatogenesis. Genome-wide RNA expression studies in ES cells expressing a V5- and GFP-tagged form of CTCFL show that genes that are downregulated in CTCFL-deficient testis are upregulated in ES cells. These data indicate that CTCFL is a male germ cell gene regulator. Furthermore, genome-wide DNA-binding analysis shows that CTCFL binds a consensus sequence that is very similar to that of CTCF. However, only ~3,700 out of the ~5,700 CTCFL- and ~31,000 CTCF-binding sites overlap. CTCFL binds promoters with loosely assembled nucleosomes, whereas CTCF favors consensus sites surrounded by phased nucleosomes. Finally, an ES cell-based rescue assay shows that CTCFL is functionally different from CTCF. CONCLUSIONS: Our data suggest that nucleosome composition specifies the genome-wide binding of CTCFL and CTCF. We propose that the transient expression of CTCFL in spermatogonia and preleptotene spermatocytes serves to occupy a subset of promoters and maintain the expression of male germ cell genes