1,216 research outputs found
Abstract Learning Frameworks for Synthesis
We develop abstract learning frameworks (ALFs) for synthesis that embody the
principles of CEGIS (counter-example based inductive synthesis) strategies that
have become widely applicable in recent years. Our framework defines a general
abstract framework of iterative learning, based on a hypothesis space that
captures the synthesized objects, a sample space that forms the space on which
induction is performed, and a concept space that abstractly defines the
semantics of the learning process. We show that a variety of synthesis
algorithms in current literature can be embedded in this general framework.
While studying these embeddings, we also generalize some of the synthesis
problems these instances are of, resulting in new ways of looking at synthesis
problems using learning. We also investigate convergence issues for the general
framework, and exhibit three recipes for convergence in finite time. The first
two recipes generalize current techniques for convergence used by existing
synthesis engines. The third technique is a more involved technique of which we
know of no existing instantiation, and we instantiate it to concrete synthesis
problems
Clades and clans: a comparison study of two evolutionary models
The Yule-Harding-Kingman (YHK) model and the proportional to distinguishable
arrangements (PDA) model are two binary tree generating models that are widely
used in evolutionary biology. Understanding the distributions of clade sizes
under these two models provides valuable insights into macro-evolutionary
processes, and is important in hypothesis testing and Bayesian analyses in
phylogenetics. Here we show that these distributions are log-convex, which
implies that very large clades or very small clades are more likely to occur
under these two models. Moreover, we prove that there exists a critical value
for each such that for a given clade with size ,
the probability that this clade is contained in a random tree with leaves
generated under the YHK model is higher than that under the PDA model if
, and lower if . Finally, we extend our results
to binary unrooted trees, and obtain similar results for the distributions of
clan sizes.Comment: 21page
Ruthenacycles and Iridacycles as Catalysts for Asymmetric Transfer Hydrogenation and Racemisation
Ruthenacycles, which are easily prepared in a single step by reaction between enantiopure aromatic amines and [Ru(arene)Cl2]2 in the presence of NaOH and KPF6, are very good asymmetric transfer hydrogenation catalysts. A range of aromatic ketones were reduced using isopropanol in good yields with ee’s up to 98%. Iridacycles, which are prepared in similar fashion from [IrCp*Cl2]2 are excellent catalysts for the racemisation of secondary alcohols and chlorohydrins at room temperature. This allowed the development of a new dynamic kinetic resolution of chlorohydrins to the enantiopure epoxides in up to 90% yield and 98% enantiomeric excess (ee) using a mutant of the enzyme Haloalcohol dehalogenase C and an iridacycle as racemisation catalyst.
Randomised, phase II trial comparing oral capecitabine (Xeloda®) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines
Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5-fluorouracil preferentially at the tumour site. This randomised, phase II trial evaluated the efficacy and safety of capecitabine or paclitaxel in patients with anthracycline-pretreated metastatic breast cancer. Outpatients with locally advanced and/or metastatic breast cancer whose disease was unresponsive or resistant to anthracycline therapy were randomised to 3-week cycles of intermittent oral capecitabine (1255 mg m−2 twice daily, days 1–14, (22 patients)) or a reference arm of i.v. paclitaxel (175 mg m−2, (20 patients)). Two additional patients were initially randomised to continuous capecitabine 666 mg m−2 twice daily, but this arm was closed following selection of the intermittent schedule for further development. Overall response rate was 36% (95% CI 17–59%) with capecitabine (including three complete responses) and 26% (95% CI 9–51%) with paclitaxel (no complete responses). Median time to disease progression was similar in the two treatment groups (3.0 months with capecitabine, 3.1 months with paclitaxel), as was overall survival (7.6 and 9.4 months, respectively). Paclitaxel was associated with more alopecia, peripheral neuropathy, myalgia and neutropenia, whereas typical capecitabine-related adverse events were diarrhoea, vomiting and hand–foot syndrome. Twenty-three per cent of capecitabine-treated patients and 16% of paclitaxel-treated patients achieved a ⩾10% improvement in Karnofsky Performance Status. Oral capecitabine is active in anthracycline-pretreated advanced/metastatic breast cancer and has a favourable safety profile. Furthermore, capecitabine provides a convenient, patient-orientated therapy
Scaling properties of protein family phylogenies
One of the classical questions in evolutionary biology is how evolutionary
processes are coupled at the gene and species level. With this motivation, we
compare the topological properties (mainly the depth scaling, as a
characterization of balance) of a large set of protein phylogenies with a set
of species phylogenies. The comparative analysis shows that both sets of
phylogenies share remarkably similar scaling behavior, suggesting the
universality of branching rules and of the evolutionary processes that drive
biological diversification from gene to species level. In order to explain such
generality, we propose a simple model which allows us to estimate the
proportion of evolvability/robustness needed to approximate the scaling
behavior observed in the phylogenies, highlighting the relevance of the
robustness of a biological system (species or protein) in the scaling
properties of the phylogenetic trees. Thus, the rules that govern the
incapability of a biological system to diversify are equally relevant both at
the gene and at the species level.Comment: Replaced with final published versio
Earliest rock fabric formed in the Solar System preserved in a chondrule rim
Rock fabrics – the preferred orientation of grains – provide a window into the history of rock formation, deformation and compaction. Chondritic meteorites are among the oldest materials in the Solar System1 and their fabrics should record a range of processes occurring in the nebula and in asteroids, but due to abundant fine-grained material these samples have largely resisted traditional in situ fabric analysis. Here we use high resolution electron backscatter diffraction to map the orientation of sub-micrometre grains in the Allende CV carbonaceous chondrite: the matrix material that is interstitial to the mm-sized spherical chondrules that give chondrites their name, and fine-grained rims which surround those chondrules. Although Allende matrix exhibits a bulk uniaxial fabric relating to a significant compressive event in the parent asteroid, we find that fine-grained rims preserve a spherically symmetric fabric centred on the chondrule. We define a method that quantitatively relates fabric intensity to net compression, and reconstruct an initial porosity for the rims of 70-80% - a value very close to model estimates for the earliest uncompacted aggregates2,3. We conclude that the chondrule rim textures formed in a nebula setting and may therefore be the first rock fabric to have formed in the Solar System
Infrared composition of the Large Magellanic Cloud
The evolution of galaxies and the history of star formation in the Universe
are among the most important topics in today's astrophysics. Especially, the
role of small, irregular galaxies in the star-formation history of the Universe
is not yet clear. Using the data from the AKARI IRC survey of the Large
Magellanic Cloud at 3.2, 7, 11, 15, and 24 {\mu}m wavelengths, i.e., at the
mid- and near-infrared, we have constructed a multiwavelength catalog
containing data from a cross-correlation with a number of other databases at
different wavelengths. We present the separation of different classes of stars
in the LMC in color-color, and color-magnitude, diagrams, and analyze their
contribution to the total LMC flux, related to point sources at different
infrared wavelengths
Topical Application of Activity-based Probes for Visualization of Brain Tumor Tissue
Several investigators have shown the utility of systemically delivered optical imaging probes to image tumors in small animal models of cancer. Here we demonstrate an innovative method for imaging tumors and tumor margins during surgery. Specifically, we show that optical imaging probes topically applied to tumors and surrounding normal tissue rapidly differentiate between tissues. In contrast to systemic delivery of optical imaging probes which label tumors uniformly over time, topical probe application results in rapid and robust probe activation that is detectable as early as 5 minutes following application. Importantly, labeling is primarily associated with peri-tumor spaces. This methodology provides a means for rapid visualization of tumor and potentially infiltrating tumor cells and has potential applications for directed surgical excision of tumor tissues. Furthermore, this technology could find use in surgical resections for any tumors having differential regulation of cysteine cathepsin activity
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