pinecone/core-2020-05-10-deduplication huggingface dataset:
Chamber behavior of double Hurwitz numbers in genus 0

AbstractWe study double Hurwitz numbers in genus zero counting the number of covers CP1→CP1 with two branching points with a given branching behavior. By the recent result due to Goulden, Jackson and Vakil, these numbers are piecewise polynomials in the multiplicities of the preimages of the branching points. We describe the partition of the parameter space into polynomiality domains, called chambers, and provide an expression for the difference of two such polynomials for two neighboring chambers. Besides, we provide an explicit formula for the polynomial in a certain chamber called totally negative, which enables us to calculate double Hurwitz numbers in any given chamber as the polynomial for the totally negative chamber plus the sum of the differences between the neighboring polynomials along a path connecting the totally negative chamber with the given one
Predictions of striking energy and angular dependence in pp→(pp)S-waveπ0 production

AbstractA phenomenological calculation from threshold to 800 MeV of the initial proton beam energy is presented to describe recent data on the reaction pp→(pp)S-waveπ0 with a low energy cut on the final state diproton excitation energy. A strong forward dip is obtained in the differential cross section as in the data from COSY at 800 MeV, although the absolute value of the forward cross section is too low. Earlier low energy data from Celsius are reasonably well reproduced. In the unexplored energy interval between these two experiments the model predicts a spectacular energy dependence both in the forward direction and in the angle-integrated cross section, which may be related to a delicate interplay of the Δ(1232) and NN background in different interfering partial wave amplitudes
Programming Hippocampal Neural Stem/Progenitor Cells into Oligodendrocytes Enhances Remyelination in the Adult Brain after Injury

SummaryDemyelinating diseases are characterized by a loss of oligodendrocytes leading to axonal degeneration and impaired brain function. Current strategies used for the treatment of demyelinating disease such as multiple sclerosis largely rely on modulation of the immune system. Only limited treatment options are available for treating the later stages of the disease, and these treatments require regenerative therapies to ameliorate the consequences of oligodendrocyte loss and axonal impairment. Directed differentiation of adult hippocampal neural stem/progenitor cells (NSPCs) into oligodendrocytes may represent an endogenous source of glial cells for cell-replacement strategies aiming to treat demyelinating disease. Here, we show that Ascl1-mediated conversion of hippocampal NSPCs into mature oligodendrocytes enhances remyelination in a diphtheria-toxin (DT)-inducible, genetic model for demyelination. These findings highlight the potential of targeting hippocampal NSPCs for the treatment of demyelinated lesions in the adult brain
Integration of copy number and transcriptomics provides risk stratification in prostate cancer : a discovery and validation cohort study

Study data are deposited in NCBI GEO (unique identifier number GSE70770).Background : Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. Methods : In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. Findings : We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer ( MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions. Interpretation : For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.Publisher PDFPeer reviewe
Yang-Mills instantons and dyons on homogeneous G(2)-manifolds

We consider LieG-valued Yang-Mills fields on the space RxG/H, where G/H is a compact nearly Kahler six-dimensional homogeneous space, and the manifold RxG/H carries a G(2)-structure. After imposing a general G-invariance condition, Yang-Mills theory with torsion on RxG/H is reduced to Newtonian mechanics of a particle moving in R-6, R-4 or R-2 under the influence of an inverted double-well-type potential for the cases G/H = SU(3)/U(1)xU(1), Sp(2)/Sp(1)xU(1) or G(2)/SU(3), respectively. We analyze all critical points and present analytical and numerical kink-and bounce-type solutions, which yield G-invariant instanton configurations on those cosets. Periodic solutions on S(1)xG/H and dyons on iRxG/H are also given.RFBR/09-02-91347DFGHeisenberg-Landau progra
Bioactivity-guided mass spectral net working reveals a new set of allbicidin derivatives from #Xanthomonas albilineans#

Albicidin is produced by the sugarcane pathogenic bacterium Xanthomonas albilineans and is a potent antibiotic specifically targeting the bacterial DNA gyrase with an IC50 value in the nanomolar range. The structure of albicidin, which has remained unsolved for more than three decades since its first description, has been solved by a combination of extensive NMR and HR-MS/MS experiments. An inherent problem for the structure elucidation was the low amount of the albicidin production in cell culture. The low production forced us to cultivate several hundred liters in order to purify a few milligrams required for NMR experiments. In comparison, LC-HR-MS/MS has the great advantage of several orders of magnitude and high sensitivity. Thus, this approach requires much less material. But more importantly, purification of compounds is not necessary for structural analysis. Due to the application of targeted LC-MS/MS experiments, we were able to propose the structure of N-terminal carba- S158 moylated and b-methoxylated albicidin derivatives. Both of them are currently chemically synthesized and studied in a medicinal chemistry campaign. In order to search for more pharmaceutically relevant albicidin derivatives, we applied non-targeted LC-HR-MS/MS approaches combined with mass spectral networking, a recently introduced approach for non-targeted MS/MS data-analysis. However, as for the structural elucidation of albicidin, the even lower concentrated derivatives resulted in difficulties to obtain useful MS/ MS spectra. Since we typically operate the mass spectrometer in data-dependent acquisition mode (DDA), it inherently selects high abundant compounds of cell extracts for MS/ MS scans and possibly ignore low abundant compounds. The same goes for the network analysis which is based on similarity of MS/MS spectra and may not take potential ion species into account. To overcome this problem, we implemented a bioactivity-guided fractionation by solid phase extraction and semi-preparative HPLC. Fractions with antibacterial activity were subsequently submitted to several LC-MS/MS runs in DDA mode with shifted survey scan windows (stitched DDA). Besides the increased amount of MS/MS events per mass range, narrowing down the m/z range of the survey scan also increased the dynamic range of the orbitrap analyzer, which enabled us to significantly increase the method's sensitivity. Finally, we were able to detect a whole series of new albicidin derivatives and to propose their structures based on exact mass determination and MS/MS fragmentation patterns. These new compounds provide great opportunities in lead optimization of albicidin as a new anti-infective drug. Apart from the pharmaceutical relevance, some of the identified by-products give us important insights into the formation of albicidin and its intriguing biosynthetic machinery. (Résumé d'auteur
The Castalia Mission to Main Belt Comet 133P/Elst-Pizarro

We describe Castalia, a proposed mission to rendezvous with a Main Belt Comet
(MBC), 133P/Elst-Pizarro. MBCs are a recently discovered population of
apparently icy bodies within the main asteroid belt between Mars and Jupiter,
which may represent the remnants of the population which supplied the early
Earth with water. Castalia will perform the first exploration of this
population by characterising 133P in detail, solving the puzzle of the MBC's
activity, and making the first in situ measurements of water in the asteroid
belt. In many ways a successor to ESA's highly successful Rosetta mission,
Castalia will allow direct comparison between very different classes of comet,
including measuring critical isotope ratios, plasma and dust properties. It
will also feature the first radar system to visit a minor body, mapping the ice
in the interior. Castalia was proposed, in slightly different versions, to the
ESA M4 and M5 calls within the Cosmic Vision programme. We describe the science
motivation for the mission, the measurements required to achieve the scientific
goals, and the proposed instrument payload and spacecraft to achieve these.Comment: Accepted for publication in Advances in Space Research (special issue
  on Small Body Exploration). 30 page
Shear in reinforced and unreinforced masonry : response, design and construction

This paper describes the vulnerability of masonry under shear; first the mechanisms of in-plane and out-of-plane shear performance of masonry are reviewed; both the unreinforced and lightly reinforced masonry wall systems are considered.  Factors affecting the response of unreinforced and reinforced masonry to shear are described and the effect of the variability of those factors to the failure mode of masonry shear walls is also discussed. Some critique is provided on the existing design provisions in various masonry standards
Stiffness of FRP pultruded tubes under repeated axial impacts

Fibre composites in deep foundation industry have been recognized to replace conventional materials such as concrete, steel and timber in harsh marine environment. The emergence of  hollow fibre reinforced polymer (FRP) composite tubes as a structural component provided the industry to consider this material as a potential composite pile type as they can carry design load. However, issue  such as driving performance of this material warrants investigation as they are considered the lowest performer  among composite piles. The thin-walled section generally ruptures under high driving stresses, thus its stiffness for post-impact performance is in question. This  paper  experimentally investigated the effects of impact energy and number of impacts on the axial stiffness of hollow FRP composite tubes. Six incident energy variants were considered, and two specimens for a given impact energy were subjected to a maximum of 130 repeated impacts using a drop-weight impact tester. The impact response and the  contact stiffness were evaluated in terms of damage 
progression and the evolution of peak force for both  collapsed and non-collapsed  tubes. Results point out that  no significant difference exists in the behaviour of the  tubes for which no collapse occurs with test duration. On the contrary, the location of the initiation of collapse influenced the shape of the load and number of impact curves for collapsed tubes. The value of the stiffness after the initiation of collapse remains the same regardless of the magnitude of the applied energy. Furthermore on the collapsed tubes, it was observed that impact energy does not significantly reduce the stiffness  of tubes during initial impacts, however, their effects were apparent as the number of impacts increases.
Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions.

The physiological role of prion protein (PrP) remains unknown. Mice devoid of PrP develop normally but are resistant to scrapie; introduction of a PrP transgene restores susceptibility to the disease. To identify the regions of PrP necessary for this activity, we prepared PrP knockout mice expressing PrPs with amino-proximal deletions. Surprisingly, PrP lacking residues 32-121 or 32-134, but not with shorter deletions, caused severe ataxia and neuronal death limited to the granular layer of the cerebellum as early as 1-3 months after birth. The defect was completely abolished by introducing one copy of a wild-type PrP gene. We speculate that these truncated PrPs may be nonfunctional and compete with some other molecule with a PrP-like function for a common ligand
An empirical comparison of alternate regime-switching models for electricity spot prices

One of the most profound features of electricity spot prices are the price spikes. Markov regime-switching (MRS) models seem to be a natural candidate for modeling this spiky behavior. However, in the studies published so far, the goodness-of-fit of the proposed models has not been a major focus. While most of the models were elegant, their fit to empirical data has either been not examined thoroughly or the signs of a bad fit ignored. With this paper we want to fill the gap. We calibrate and test a range of MRS models in an attempt to find parsimonious specifications that not only address the main characteristics of electricity prices but are statistically sound as well. We find that the most universal and robust structure is that of an independent spike 3-regime model with heteroscedastic diffusion-type base regime dynamics and shifted spike regime distributions.
Martingale properties of self-enforcing debt

Not-too-tight (NTT) debt limits are endogenous restrictions on debt that prevent agents from defaulting and opting for a specified continuation utility, while allowing for maximal credit expansion (Alvarez and Jermann, 2000). For an agent facing some fixed prices for the Arrow securities, we prove that discounted NTT debt limits must differ by a martingale. Discounted debt limits are submartingales/martingales under an interdiction to trade/borrow, and can be supermartingales under a temporary interdiction to trade. With high interest rates and borrowing limited by the agent's ability to repay debt out of his future endowments, nonpositive NTT debt limits are unique. With low interest rates, bubbles limited by the size of the total martingale components in debt limits can be sustained in equilibrium. Bubbles arise in response to debt limits more restrictive (at the prevailing interest rates) than the total amount of self-enforcing debt allowed by the underlying enforcement limitations.
Phase II study of capecitabine and mitomycin C as first-line treatment in patients with advanced colorectal cancer

This study was designed to assess the safety and efficacy of capecitabine and mitomycin C (MMC) in previously untreated patients with advanced colorectal cancer (CRC). Patients received capecitabine 2500 mg m2 day 1, orally divided in two doses of 1250 mg m-2 in the morning and evening for 14 days every 21 days and MMC 7 mg m-2 (maximum total dose 14 mg) as an intravenous bolus every 6 weeks for a total of four courses. The median age was 70 years (range 24–85) and the majority of patients (86.9%) were of performance status 1/2. The most common metastatic site was liver. In all, 84 patients were assessable for response. The overall response rate was 38% (95% CI: 27.7–49.3) and a further 33.3% of patients achieved stable disease over 12 weeks. There was good symptom resolution ranging from 64 to 86%. Grade 3/4 toxicity was as follows: hand–foot syndrome 19.7%; diarrhoea 10%; neutropenia 2.4%; infection 2.3%. Capecitabine and MMC have shown encouraging activity with a favourable toxicity profile, a convenient administration schedule, and could be considered for patients deemed unsuitable for oxaliplatin and irinotecan combinations.S Rao, D Cunningham, T Price, M E Hill, P J Ross, N Tebbutt, A R Norman, J Oates and P Shellit
Cell-free protein synthesis of membrane (1,3)-beta-D-glucan (curdlan) synthase: Co-translational insertion in liposomes and reconstitution in nanodiscs

A membrane-embedded curdlan synthase (CrdS) from Agrobacterium is believed to catalyse a repetitive addition of glucosyl residues from UDP-glucose to produce the (1,3)-β-d-glucan (curdlan) polymer. We report wheat germ cell-free protein synthesis (WG-CFPS) of full-length CrdS containing a 6xHis affinity tag and either Factor Xa or Tobacco Etch Virus proteolytic sites, using a variety of hydrophobic membrane-mimicking environments. Full-length CrdS was synthesised with no variations in primary structure, following analysis of tryptic fragments by MALDI-TOF/TOF Mass Spectrometry. Preparative scale WG-CFPS in dialysis mode with Brij-58 yielded CrdS in mg/ml quantities. Analysis of structural and functional properties of CrdS during protein synthesis showed that CrdS was co-translationally inserted in DMPC liposomes during WG-CFPS, and these liposomes could be purified in a single step by density gradient floatation. Incorporated CrdS exhibited a random orientation topology. Following affinity purification of CrdS, the protein was reconstituted in nanodiscs with Escherichia coli lipids or POPC and a membrane scaffold protein MSP1E3D1. CrdS nanodiscs were characterised by small-angle X-ray scattering using synchrotron radiation and the data obtained were consistent with insertion of CrdS into bilayers. We found CrdS synthesised in the presence of the Ac-AAAAAAD surfactant peptide or co-translationally inserted in liposomes made from E. coli lipids to be catalytically competent. Conversely, CrdS synthesised with only Brij-58 was inactive. Our findings pave the way for future structural studies of this industrially important catalytic membrane protein.Agalya Periasamy, Nadim Shadiac, Amritha Amalraj, Soňa Garajová, Yagnesh Nagarajan, Shane Waters, Haydyn D.T. Mertens, Maria Hrmov
Repurposing — a ray of hope in tackling extensively drug resistance in tuberculosis

Tuberculosis (TB) remains a serious concern more than two decades on from when the World Health Organization declared it a global health emergency. The alarming rise of antibiotic resistance in Mycobacterium tuberculosis, the etiological agent of TB, has made it exceedingly difficult to control the disease with the existing portfolio of anti-TB chemotherapy. The development of effective drugs with novel mechanism(s) of action is thus of paramount importance to tackle drug resistance. The development of novel chemical entities requires more than 10 years of research, requiring high-risk investment to become commercially available. Repurposing pre-existing drugs offers a solution to circumvent this mammoth investment in time and funds. In this context, several drugs with known safety and toxicity profiles have been evaluated against the TB pathogen and found to be efficacious against its different physiological states. As the endogenous targets of these drugs in the TB bacillus are most likely to be novel, there is minimal chance of cross-resistance with front-line anti-TB drugs. Also, reports that some of these drugs may potentially have multiple targets means that the possibility of the development of resistance against them is minimal. Thus repurposing existing molecules offers immense promise to tackle extensively drug-resistant TB infections
Search for single production of vector-like quarks decaying into a b quark and a W boson in proton-proton collisions at $\sqrt{s} = 13$ TeV

A search is presented for a heavy vector-like quark, decaying into a b quark and a W boson, which is produced singly in association with a light flavor quark and a b quark. The analysis is performed using a data sample of proton–proton collisions at a center-of-mass energy of $\sqrt{s} = 13$ TeV collected at the LHC in 2015. The data set used in the analysis corresponds to an integrated luminosity of 2.3 $fb^{−1}$. The search is carried out using events containing one electron or muon, at least one b-tagged jet with large transverse momentum, at least one jet in the forward region of the detector, and missing transverse momentum. No excess over the standard model prediction is observed. Upper limits are placed on the production cross section of heavy exotic quarks: a T quark with a charge of 2/3, and a Y quark with a charge of −4/3. For Y quarks with coupling of 0.5 and $\mathcal{B}(Y→bW) = 100%$, the observed (expected) lower mass limits are 1.40 (1.0)TeV. This is the most stringent limit to date on the single production of the Y vector-like quark
Prefrontal cortex connectivity dysfunction in performing the Fist-Edge-Palm task in patients with first-episode schizophrenia and non-psychotic first-degree relatives

Neurological soft signs have been considered one of the promising neurological endophenotypes for schizophrenia. However, most previous studies have employed clinical rating data only. The present study aimed to examine the neurobiological basis of one of the typical motor coordination signs, the Fist–Edge–Palm (FEP) task, in patients with first-episode schizophrenia and their non-psychotic first degree relatives. Thirteen patients with first-episode schizophrenia, 14 non-psychotic first-degree relatives and 14 healthy controls were recruited. All of them were instructed to perform the FEP task in a 3 T GE Machine. Psychophysiological interaction (PPI) analysis was used to evaluate the functional connectivity between the sensorimotor cortex and frontal regions when participants performed the FEP task compared to simple motor tasks. In the contrast of palm-tapping (PT) vs. rest, activation of the left frontal–parietal region was lowest in the schizophrenia group, intermediate in the relative group and highest in the healthy control group. In the contrast of FEP vs. PT, patients with schizophrenia did not show areas of significant activation, while relatives and healthy controls showed significant activation of the left middle frontal gyrus. Moreover, with the increase in task complexity, significant functional connectivity was observed between the sensorimotor cortex and the right frontal gyrus in healthy controls but not in patients with first episode schizophrenia. These findings suggest that activity of the left frontal–parietal and frontal regions may be neurofunctional correlates of neurological soft signs, which in turn may be a potential endophenotype of schizophrenia. Moreover, the right frontal gyrus may play a specific role in the execution of the FEP task in schizophrenia spectrum disorders.Full Tex