Variability of Pennsylvanian-Permian Carbonate Associations and Implications for NW Pangea Palaeogeography, East-Central British Columbia, Canada

Different stages of Pennsylvanian-Permian carbonate sedimentation in east-central British Columbia record a complex history of changing environments influenced by evolving palaeogeography and climate. Newly recognized tectonically controlled features affected the distribution and variability of carbonate associations, providing new interpretations for this portion of the west coast of Pangea. Both a heterozoan (cool water) and photozoan (warm-water) association were identified on either side of a palaeogeographic high here informally termed “Tipinahokan Peninsula”. Cool water carbonates were located outboard, or to the west of this high, an area influenced by upwelling waters. Inboard of this high, a warm, protected sea developed, here termed “Kisosowin Sea”. This configuration and palaeolatitude is similar to that of Baja California, Mexico and the Sea of Cortéz, providing a good modern analog for these deposits where warm water carbonates grow at latitudes otherwise dominated by cool water deposits. The warm sea provided a place for a photozoan association to develop during the Permian when the low latitude NW coast of Pangea was dominated by cool water carbonates

Algebraic-matrix calculation of vibrational levels of triatomic molecules

We introduce an accurate and efficient algebraic technique for the computation of the vibrational spectra of triatomic molecules, of both linear and bent equilibrium geometry. The full three-dimensional potential energy surface (PES), which can be based on entirely {\it ab initio} data, is parameterized as a product Morse-cosine expansion, expressed in bond-angle internal coordinates, and includes explicit interactions among the local modes. We describe the stretching degrees of freedom in the framework of a Morse-type expansion on a suitable algebraic basis, which provides exact analytical expressions for the elements of a sparse Hamiltonian matrix. Likewise, we use a cosine power expansion on a spherical harmonics basis for the bending degree of freedom. The resulting matrix representation in the product space is very sparse and vibrational levels and eigenfunctions can be obtained by efficient diagonalization techniques. We apply this method to carbonyl sulfide OCS, hydrogen cyanide HCN, water H$_2$O, and nitrogen dioxide NO$_2$. When we base our calculations on high-quality PESs tuned to the experimental data, the computed spectra are in very good agreement with the observed band origins.Comment: 11 pages, 2 figures, containg additional supporting information in epaps.ps (results in tables, which are useful but not too important for the paper

Acoustic identification of Mexican bats based on taxonomic and ecological constraints on call design

1. Monitoring global biodiversity is critical for understanding responses to anthropogenic change, but biodiversity monitoring is often biased away from tropical, megadiverse areas that are experiencing more rapid environmental change. Acoustic surveys are increasingly used to monitor biodiversity change, especially for bats as they are important indicator species and most use sound to detect, localise and classify objects. However, using bat acoustic surveys for monitoring poses several challenges, particularly in mega-diverse regions. Many species lack reference recordings, some species have high call similarity or differ in call detectability, and quantitative classification tools, such as machine learning algorithms, have rarely been applied to data from these areas. 2. Here, we collate a reference call library for bat species that occur in a megadiverse country, Mexico. We use 4,685 search-phase calls from 1,378 individual sequences of 59 bat species to create automatic species identification tools generated by machine learning algorithms (Random Forest). We evaluate the improvement in species-level classification rates gained by using hierarchical classifications, reflecting either taxonomic or ecological constraints (guilds) on call design, and examine how classification rate accuracy changes at different hierarchical levels (family, genus, and guild). 3. Species-level classification of calls had a mean accuracy of 66% and the use of hierarchies improved mean species-level classification accuracy by up to 6% (species within families 72%, species within genera 71.2% and species within guilds 69.1%). Classification accuracy to family, genus and guild-level was 91.7%, 77.8% and 82.5%, respectively. 4. The bioacoustic identification tools we have developed are accurate for rapid biodiversity assessments in a megadiverse region and can also be used effectively to classify species at broader taxonomic or ecological levels. This flexibility increases their usefulness when there are incomplete species reference recordings and also offers the opportunity to characterise and track changes in bat community structure. Our results show that bat bioacoustic surveys in megadiverse countries have more potential than previously thought to monitor biodiversity changes and can be used to direct further developments of bioacoustic monitoring programs in Mexico

Lateral Gene Expression in Drosophila Early Embryos Is Supported by Grainyhead-Mediated Activation and Tiers of Dorsally-Localized Repression

The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind), a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence (“the A-box”) present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh), a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic) also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator) and Cic (repressor) may also support a “switch-like” response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo

A multicenter phase III trial comparing irinotecan-gemcitabine (IG) with gemcitabine (G) monotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer

Our purpose was to determine the response rate and median and overall survival of gemcitabine as monotherapy versus gemcitabine plus irinotecan in advanced or metastatic pancreatic cancer. Patients with histologically or cytologically confirmed adenocarcinoma who were chemotherapy and radiotherapy naive were enrolled. Patients were centrally randomised at a one-to-one ratio to receive either gemcitabine monotherapy (900 mg m−2 on days 1, 8 and 15 every 4 weeks (arm G), or gemcitabine (days 1 and 8) plus irinotecan (300 mg m−2 on day 8) (arm IG), repeated every 3 weeks. The total number of cycles administered was 255 in the IG arm and 245 in the G arm; the median number of cycles was 3. In all, 145 patients (71 in arm IG and 74 in arm G) were enrolled; 60 and 70 patients from arms IG and G, respectively, were evaluable. A complete clinical response was achieved in three (4.3%) arm G patients; nine (15%) patients in arm IG and four (5.7%) in arm G achieved a partial response. The overall response rate was: arm IG 15% and arm G 10% (95% CI 5.96–24.04 and 95% CI 2.97–17.03, respectively; P=0.387). The median time to tumour progression was 2.8 months and 2.9 months and median survival time was 6.4 and 6.5 months for the IG and G arms, respectively. One-year survival was 24.3% for the IG arm and 21.8% for the G arm. No statistically significant difference was observed comparing gemcitabine monotherapy versus gemcitabine plus irinotecan in the treatment of advanced pancreatic cancer, with respect to overall and 1-year survival

Dynamic Interpretation of Hedgehog Signaling in the Drosophila Wing Disc

Morphogens are classically defined as molecules that control patterning by acting at a distance to regulate gene expression in a concentration-dependent manner. In the Drosophila wing imaginal disc, secreted Hedgehog (Hh) forms an extracellular gradient that organizes patterning along the anterior–posterior axis and specifies at least three different domains of gene expression. Although the prevailing view is that Hh functions in the Drosophila wing disc as a classical morphogen, a direct correspondence between the borders of these patterns and Hh concentration thresholds has not been demonstrated. Here, we provide evidence that the interpretation of Hh signaling depends on the history of exposure to Hh and propose that a single concentration threshold is sufficient to support multiple outputs. Using mathematical modeling, we predict that at steady state, only two domains can be defined in response to Hh, suggesting that the boundaries of two or more gene expression patterns cannot be specified by a static Hh gradient. Computer simulations suggest that a spatial “overshoot” of the Hh gradient occurs, i.e., a transient state in which the Hh profile is expanded compared to the Hh steady-state gradient. Through a temporal examination of Hh target gene expression, we observe that the patterns initially expand anteriorly and then refine, providing in vivo evidence for the overshoot. The Hh gene network architecture suggests this overshoot results from the Hh-dependent up-regulation of the receptor, Patched (Ptc). In fact, when the network structure was altered such that the ptc gene is no longer up-regulated in response to Hh-signaling activation, we found that the patterns of gene expression, which have distinct borders in wild-type discs, now overlap. Our results support a model in which Hh gradient dynamics, resulting from Ptc up-regulation, play an instructional role in the establishment of patterns of gene expression

Understanding valuation of travel time changes: are preferences different under different stated choice design settings?

Stated choice (SC) experiments are the most popular method to estimate the value of travel time changes (VTTC) of a population. In the simplest VTTC experiment, the SC design variables are time changes and cost changes. The levels of these variables create a particular setting from which preferences are inferred. This paper tries to answer the question “do preferences vary with SC settings?”. For this, we investigate the role of the variables used in the SC experiment on the estimation of the set of VTTC (i.e. mean and covariates). Ideally, one would like to observe the same individuals completing different SC experiments. Since that option is not available, an alternative approach is to use a large dataset of responses, and split it according to different levels of the variable of interest. We refer to this as partial data analysis. The estimation of the same model on each sub-sample provides insights into potential effects of the variable of interest. This approach is applied in relation to three design variables on the data for the last national VTTC study in the UK, using state-of-the-art model specifications. The results show several ways in which the estimated set of VTTC can be affected by the levels of SC design variables. We conclude that model estimates (including the VTTC and covariates) are different in different settings. Hence by focussing the survey on specific settings, sample level results will be affected accordingly. Our findings have implications for appraisal and can inform the construction of future SC experiments

Robust Target Gene Discovery through Transcriptome Perturbations and Genome-Wide Enhancer Predictions in Drosophila Uncovers a Regulatory Basis for Sensory Specification

CisTarget X is a novel computational method that accurately predicts Atonal governed regulatory networks in the retina of the fruit fly

Second-line treatment with irinotecan plus cisplatin vs cisplatin of patients with advanced non-small-cell lung cancer pretreated with taxanes and gemcitabine: a multicenter randomised phase II study

The aim of this study was to compare the irinotecan/cisplatin regimen with cisplatin as second-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) pretreated with a taxane/gemcitabine regimen. Patients (n=147) with stage IV NSCLC pretreated with a taxane/gemcitabine regimen were randomly assigned to receive either irinotecan (110 mg m−2, day 1 and 100 mg m−2, day 8) and cisplatin (80 mg m−2, day 8) (IC; n=74) or CDDP (80 mg m−2, day 1) (C; n=73) every 3 weeks. Patients treated with IC and C had a median survival of 7.8 and 8.8 months, respectively (P=0.933). The 1-year survival rate was 34.3% for IC-treated patients and 31.7% for C-treated patients. Cox's regression analysis revealed that response to treatment (hazard ratio (HR)=2.787; 95% confidence interval (CI): 1.1578–4.922) and performance status (HR=1.865; 95% CI: 1.199–2.872) was independent prognostic factors for survival. Overall response rate was 22.5% (95% CI: 12.8–32.2%) for IC-treated patients and 7.0% (95% CI: 1.15–13.6%) for C-treated patients (P=0.012); tumour growth control (partial remission (PR)+stable disease (SD)) was observed in 26 (38%) IC and 25 (36%) C patients (P=0.878). There was no difference in terms of quality of life between the two chemotherapy arms. The incidence of febrile neutropenia, grade 3 and 4 neutropenia and grade 3 and 4 diarrhoea was significantly higher in the IC- than the C-treated patients. Other toxicities were mild. There were no treatment-related deaths in either arm. The IC regimen did not confer a survival benefit compared with C as second-line treatment of patients with advanced NSCLC pretreated with a taxane/gemcitabine regimen, despite its better efficacy in terms of response rate