julilili42/papers huggingface dataset:
Serial crystallography onin vivogrown microcrystals using synchrotron radiation
2014-01-23

Crystal structure determinations of biological macromolecules are limited by the availability of sufficiently sized crystals and by the fact that crystal quality deteriorates during data collection owing to radiation damage. Exploiting a micrometre-sized X-ray beam, high-precision diffractometry and shutterless data acquisition with a pixel-array detector, a strategy for collecting data from many micrometre-sized crystals presented to an X-ray beam in a vitrified suspension is demonstrated. By combining diffraction data from 80 Trypanosoma brucei procathepsin B crystals with an average volume of 9 μm 3 , a complete data set to 3.0 Å resolution has been assembled. The data allowed the refinement of a structural model that is consistent with that previously obtained using free-electron laser radiation, providing mutual validation. Further improvements of the serial synchrotron crystallography technique and its combination with serial femtosecond crystallography are discussed that may allow the determination of high-resolution structures of micrometre-sized crystals.
TERRESTRIAL PLANET FORMATION IN A PROTOPLANETARY DISK WITH A LOCAL MASS DEPLETION: A SUCCESSFUL SCENARIO FOR THE FORMATION OF MARS
2014-01-23

Models of terrestrial planet formation for our solar system have been successful in producing planets with masses and orbits similar to those of Venus and Earth. However, these models have generally failed to produce Mars-sized objects around 1.5 AU. The body that is usually formed around Mars' semimajor axis is, in general, much more massive than Mars. Only when Jupiter and Saturn are assumed to have initially very eccentric orbits (e similar to 0.1), which seems fairly unlikely for the solar system, or alternately, if the protoplanetary disk is truncated at 1.0 AU, simulations have been able to produce Mars-like bodies in the correct location. In this paper, we examine an alternative scenario for the formation of Mars in which a local depletion in the density of the protosolar nebula results in a non-uniform formation of planetary embryos and ultimately the formation ofMars-sized planets around 1.5 AU. We have carried out extensive numerical simulations of the formation of terrestrial planets in such a disk for different scales of the local density depletion, and for different orbital configurations of the giant planets. Our simulations point to the possibility of the formation of Mars-sized bodies around 1.5 AU, specifically when the scale of the disk local mass-depletion is moderately high (50%-75%) and Jupiter and Saturn are initially in their current orbits. In these systems, Mars-analogs are formed from the protoplanetary materials that originate in the regions of disk interior or exterior to the local mass-depletion. Results also indicate that Earth-sized planets can form around 1 AU with a substantial amount of water accreted via primitive water-rich planetesimals and planetary embryos. We present the results of our study and discuss their implications for the formation of terrestrial planets in our solar system.
Reactivating Memories during Sleep by Odors: Odor Specificity and Associated Changes in Sleep Oscillations
2014-01-23

Abstract Memories are reactivated during sleep. Re-exposure to olfactory cues during sleep triggers this reactivation and improves later recall performance. Here, we tested if the effects of odor-induced memory reactivations are odor-specific, that is, requiring the same odor during learning and subsequent sleep. We also tested whether odor-induced memory reactivation affects oscillatory EEG activity during sleep, as a putative mechanism underlying memory processing during sleep. Participants learned a visuospatial memory task under the presence of an odor. During subsequent SWS, the same odor, a different odor, or an odorless vehicle was presented. We found that odor re-exposure during sleep significantly improves memory only when the same odor was presented again, whereas exposure to a new odor or the odorless vehicle had no effect. The memory-enhancing effect of the congruent odor was accompanied by significant increases in frontal delta (1.5–4.5 Hz) and parietal fast spindle (13.0–15.0 Hz) power as well as by an increased negative-to-positive slope of the frontal slow oscillation. Our results indicate that odor-induced memory reactivations are odor specific and trigger changes in slow-wave and spindle power possibly reflecting a bottom–up influence of hippocampal memory replay on cortical slow oscillations as well as thalamo-cortical sleep spindles.
High‐resolution metabolite imaging of light and dark treated retina using MALDI‐FTICR mass spectrometry
2014-01-23

MS imaging ( MSI ) is a valuable tool for diagnostics and systems biology studies, being a highly sensitive, label‐free technique capable of providing comprehensive spatial distribution of different classes of biomolecules. The application of MSI to the study of endogenous compounds has received considerable attention because metabolites are the result of the interactions of a biosystem with its environment. MSI can therefore enhance understanding of disease mechanisms and elucidate mechanisms for biological variation. We present the in situ comparative metabolomics imaging data for analyses of light‐ and dark‐treated retina using MALDI‐FTICR. A wide variety of tissue metabolites were imaged at a high spatial resolution. These include nucleotides, central carbon metabolism pathway intermediates, 2‐oxocarboxylic acid metabolism, oxidative phosphorylation, glycerophospholipid metabolism, and cysteine and methionine metabolites. The high lateral resolution enabled the differentiation of retinal layers, allowing determination of the spatial distributions of different endogenous compounds. A number of metabolites demonstrated differences between light and dark conditions. These findings add to the understanding of metabolic activity in the retina.
Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion
2014-01-23

Abstract Gene regulatory interactions underlying the early stages of non-genotoxic carcinogenesis are poorly understood. Here, we have identified key candidate regulators of phenobarbital (PB)-mediated mouse liver tumorigenesis, a well-characterized model of non-genotoxic carcinogenesis, by applying a new computational modeling approach to a comprehensive collection of in vivo gene expression studies. We have combined our previously developed motif activity response analysis (MARA), which models gene expression patterns in terms of computationally predicted transcription factor binding sites with singular value decomposition (SVD) of the inferred motif activities, to disentangle the roles that different transcriptional regulators play in specific biological pathways of tumor promotion. Furthermore, transgenic mouse models enabled us to identify which of these regulatory activities was downstream of constitutive androstane receptor and β-catenin signaling, both crucial components of PB-mediated liver tumorigenesis. We propose novel roles for E2F and ZFP161 in PB-mediated hepatocyte proliferation and suggest that PB-mediated suppression of ESR1 activity contributes to the development of a tumor-prone environment. Our study shows that combining MARA with SVD allows for automated identification of independent transcription regulatory programs within a complex in vivo tissue environment and provides novel mechanistic insights into PB-mediated hepatocarcinogenesis.
ON FLATTENING ELIMINATION RULES
2014-01-23

Abstract In proof-theoretic semantics of intuitionistic logic it is well known that elimination rules can be generated from introduction rules in a uniform way. If introduction rules discharge assumptions, the corresponding elimination rule is a rule of higher level, which allows one to discharge rules occurring as assumptions. In some cases, these uniformly generated elimination rules can be equivalently replaced with elimination rules that only discharge formulas or do not discharge any assumption at all—they can be flattened in a terminology proposed by Read. We show by an example from propositional logic that not all introduction rules have flat elimination rules. We translate the general form of flat elimination rules into a formula of second-order propositional logic and demonstrate that our example is not equivalent to any such formula. The proof uses elementary techniques from propositional logic and Kripke semantics.
Preparation and Crystal Structure of Ba4MgF2(CN2)4
2014-01-23

Abstract Ba 4 MgF 2 (CN 2 ) 4 was prepared by solid state metathesis reaction from metal fluorides and sodium carbodiimide in a fused copper ampoule at 650 °C. The crystal structure was refined by single‐crystal X‐ray diffraction in the space group P 2 1 / c with unit cell dimensions a = 835.1(2) pm, b = 861.7(1) pm, c = 844.2(2) pm, and β = 109.09(2)°. A characteristic feature in the crystal structure of Ba 4 MgF 2 (CN 2 ) 4 is the two‐dimensional arrangement of infinite [Mg(CN 2 ) 4/2 (CN 2 ) 2 ] layers along the bc plane of the structure. Barium and fluoride ions are situated in‐between these layers.
Upregulation of KCNQ1/KCNE1 K + channels by Klotho
2014-01-23

Klotho is a transmembrane protein expressed primarily in kidney, parathyroid gland, and choroid plexus. The extracellular domain could be cleaved off and released into the systemic circulation. Klotho is in part effective as β-glucuronidase regulating protein stability in the cell membrane. Klotho is a major determinant of aging and life span.Overexpression of Klotho increases and Klotho deficiency decreases life span. Klotho deficiency may further result in hearing loss and cardiac arrhythmia. The present study explored whether Klotho modifies activity and protein abundance of KCNQ1/KCNE1, a K(+) channel required for proper hearing and cardiac repolarization. To this end, cRNA encoding KCNQ1/KCNE1 was injected in Xenopus oocytes with or without additional injection of cRNA encoding Klotho. KCNQ1/KCNE1 expressing oocytes were treated with human recombinant Klotho protein (30 ng/mL) for 24 h. Moreover, oocytes which express both KCNQ1/KCNE1 and Klotho were treated with 10 μM DSA L (D-saccharic acid-1,4-lactone), a β-glucuronidase inhibitor. The KCNQ1/KCNE1 depolarization-induced current (I(Ks)) was determined utilizing dual electrode voltage clamp, while KCNQ1/KCNE1 protein abundance in the cell membrane was visualized utilizing specific antibody binding and quantified by chemiluminescence. KCNQ1/KCNE1 channel activity and KCNQ1/KCNE1 protein abundance were upregulated by coexpression of Klotho. The effect was mimicked by treatment with human recombinant Klotho protein (30 ng/mL) and inhibited by DSA L (10 μM). In conclusion, Klotho upregulates KCNQ1/KCNE1 channel activity by “mainly” enhancing channel protein abundance in the plasma cell membrane, an effect at least partially mediated through the β-glucuronidase activity of Klotho protein.
Shaping the Skin: The Interplay of Mesoscale Geometry and Corneocyte Swelling
2014-01-24

The stratum corneum, the outer layer of mammalian skin, provides a remarkable barrier to the external environment, yet it has highly variable permeability properties where it actively mediates between inside and out. On prolonged exposure to water, swelling of the corneocytes (skin cells composed of keratin intermediate filaments) is the key process by which the stratum corneum controls permeability and mechanics. As for many biological systems with intricate function, the mesoscale geometry is optimized to provide functionality from basic physical principles. Here we show that a key mechanism of corneocyte swelling is the interplay of mesoscale geometry and thermodynamics: given helical tubes with woven geometry equivalent to the keratin intermediate filament arrangement, the balance of solvation free energy and elasticity induces swelling of the system, importantly with complete reversibility. Our result remarkably replicates macroscopic experimental data of native through to fully hydrated corneocytes. This finding not only highlights the importance of patterns and morphology in nature but also gives valuable insight into the functionality of skin.
Complete Genome Sequence of the Sugar Cane Endophyte Pseudomonas aurantiaca PB-St2, a Disease-Suppressive Bacterium with Antifungal Activity toward the Plant Pathogen Colletotrichum falcatum
2014-01-24

ABSTRACT The endophytic bacterium Pseudomonas aurantiaca PB-St2 exhibits antifungal activity and represents a biocontrol agent to suppress red rot disease of sugar cane. Here, we report the completely sequenced 6.6-Mb genome of P. aurantiaca PB-St2. The sequence contains a repertoire of biosynthetic genes for secondary metabolites that putatively contribute to its antagonistic activity and its plant-microbe interactions.
Draft Genome Sequence of the Microbispora sp. Strain ATCC-PTA-5024, Producing the Lantibiotic NAI-107
2014-01-24

ABSTRACT We report the draft genome sequence of Microbispora sp. strain ATCC-PTA-5024, a soil isolate that produces NAI-107, a new lantibiotic with the potential to treat life-threatening infections caused by multidrug-resistant Gram-positive pathogens. The draft genome of strain Microbispora sp. ATCC-PTA-5024 consists of 8,543,819 bp, with a 71.2% G+C content and 7,860 protein-coding genes.
Active Biomechanical Rider Model for Motorcycle Simulation
2014-01-24

This chapter describes some basic principles of biomechanical full-body models and human motor control principles. It explains how they can be applied in multibody models to simulate moving virtual humans. The chapter focuses on the biomechanical active rider model which has been developed by Biomotion Solutions. It discusses some basic aspects of how the human body processes sensory input in order to find a suitable muscle activation pattern to perform desired motions. SIMPACK is often used in automotive or wheel-rail simulation. The simulation is based on three models: the human body, the motorcycle and the motion control model. The chapter presents some simulation results to demonstrate how the biomechanical rider model is used to identify parameters of rider vibration characteristics, to investigate the influence of the rider's biomechanical parameters on the dynamic ride stability and to perform some ride simulations with road excitations to calculate the ride comfort.
Cardiovascular magnetic resonance risk stratification in patients with clinically suspected myocarditis
2014-01-26

In our unselected population of consecutive patients referred for CMR work-up of clinically suspected myocarditis, patients with normal CMR have a good prognosis independent of their clinical symptoms and other findings.
Effect of T‐DNA insertions on mRNA transcript copy numbers upstream and downstream of the insertion site in Arabidopsis thaliana explored by surface enhanced Raman spectroscopy
2014-01-26

Summary We report the effect of a T ‐ DNA insertion on the expression level of mRNA transcripts of the TWISTED DWARF 1 ( TWD1 ) gene upstream and downstream of the T ‐ DNA insertion site in Arabidopsis. A novel approach based on surface‐enhanced Raman spectroscopy ( SERS ) was developed to detect and quantify the effect of a T ‐ DNA insertion on mRNA transcript accumulation at 5′‐ and 3′‐ends of the TWD1 gene. A T ‐ DNA insertion mutant in the TWD 1 gene ( twd1‐2 ) was chosen to test the sensitivity and the feasibility of the approach. The null mutant of the FK506‐like immunophilin protein TWD 1 in Arabidopsis shows severe dwarfism and strong disoriented growth of plant organs. A spontaneous arising suppressor allele of twd1‐2 called twd‐sup displayed an intermediate phenotype between wild type and the knockout phenotype of twd1‐2 . Both twd1 mutant alleles have identical DNA sequences at the TWD 1 locus including the T ‐ DNA insertion in the fourth intron of the TWD 1 gene but they show clear variability in the mutant phenotype. We present here the development and application of SERS ‐based mRNA detection and quantification using the expression of the TWD 1 gene in wild type and both mutant alleles. The hallmarks of our SERS approach are a robust and fast assay to detect up to 0.10 f m of target molecules including the ability to omit in vitro transcription and amplification steps after RNA isolation. Instead we perform direct quantification of RNA molecules. This enables us to detect and quantify rare RNA molecules at high levels of precision and sensitivity.
The long helical jet of the Lighthouse nebula, IGR J11014-6103
2014-01-27

Jets from rotation-powered pulsars have so far only been observed in systems\\nmoving subsonically trough their ambient medium and/or embedded in their\\nprogenitor supernova remnant (SNR). Supersonic runaway pulsars are also\\nexpected to produce jets, but they have not been confirmed so far. We\\ninvestigated the nature of the jet-like structure associated to the INTEGRAL\\nsource IGR J11014-6103 (the "Lighthouse nebula"). The source is a neutron star\\nescaping its parent SNR MSH 11-61A supersonically at a velocity exceeding 1000\\nkm/s. We observed the Lighthouse nebula and its jet-like X-ray structure\\nthrough dedicated high spatial resolution observations in X-rays (Chandra) and\\nradio band (ATCA). Our results show that the feature is a true pulsar's jet. It\\nextends highly collimated over &gt;11pc, displays a clear precession-like\\nmodulation, and propagates nearly perpendicular to the system direction of\\nmotion, implying that the neutron star's spin axis in IGR J11014-6103 is almost\\nperpendicular to the direction of the kick received during the supernova\\nexplosion. Our findings suggest that jets are common to rotation-powered\\npulsars, and demonstrate that supernovae can impart high kick velocities to\\nmisaligned spinning neutron stars, possibly through distinct, exotic,\\ncore-collapse mechanisms.\\n
H.E.S.S. observations of the Crab during its March 2013 GeV gamma-ray flare
2014-01-27

Context. On March 4, 2013, the Fermi-LAT and AGILE reported a flare from the direction of the Crab Nebula in which the high-energy (HE; E &gt; 100 MeV) flux was six times above its quiescent level. Simultaneous observations in other energy bands give us hints about the emission processes during the flare episode and the physics of pulsar wind nebulae in general. Aims. We search for variability of the emission of the Crab Nebula at very-high energies (VHE; E &gt; 100 GeV), using contemporaneous data taken with the H.E.S.S. array of Cherenkov telescopes. Methods. Observational data taken with the H.E.S.S. instrument on five consecutive days during the flare were analysed concerning the flux and spectral shape of the emission from the Crab Nebula. Night-wise light curves are presented with energy thresholds of 1 TeV and 5 TeV. Results. The observations conducted with H.E.S.S. on 2013 March 6 to March 10 show no significant changes in the flux. They limit the variation on the integral flux above 1 TeV to less than 63% and the integral flux above 5 TeV to less than 78% at a 95% confidence level.
Neurofilament Heavy polypeptide CpG island methylation associates with prognosis of renal cell carcinoma and prediction of antivascular endothelial growth factor therapy response
2014-01-27

Abstract Neurofilament Heavy polypeptid ( NEFH ) belongs to the group of type IV intermediate filament proteins. DNA methylation of the NEFH promoter and loss of expression have previously been shown to activate the AKT/β‐catenin pathway in tumor cells. When identifying hypermethylation of the NEFH CpG island (CGI) in renal cell cancer (RCC) we asked whether methylation could provide clinical or prognostic information for RCC and/or predict therapy response in patients with metastatic RCC ( mRCC ) undergoing antiangiogenic therapy. Relative methylation of the NEFH CGI was analyzed in 132 RCC samples and 83 paired normal tissues using quantitative methylation‐specific PCR. Results were statistically compared with tumor histology, clinicopathological parameters, progression‐free survival (PFS) as well as with overall survival (OS) in a subset of 18 mRCC patients following antiangiogenic therapy regimens. The NEFH CGI methylation demonstrated a tumor‐specific increase ( P &lt; 0.001), association with advanced disease ( P &lt; 0.001), and distant metastasis ( P = 0.005). Higher relative methylation was also significantly associated with a poor PFS (HR = 8.6, P &lt; 0.001) independent from the covariates age, gender, diameter of tumors, state of advanced disease, and local and distant metastasis. Median OS following targeted therapy was 29.8 months for patients with low methylation versus 9.8 months for the group with high methylation ( P = 0.028). We identified NEFH methylation as a candidate epigenetic marker for prognosis of RCC patients as well as prediction of anti‐vascular endothelial growth factor‐based therapy response.
Insights to controls on dolomitization by means of reactive transport models applied to the Benicàssim case study (Maestrat Basin, eastern Spain)
2014-01-27

Partially dolomitized carbonate rocks of the Middle East and North America host large hydrocarbon reserves. The origin of some of these dolomites has been attributed to a hydrothermal mechanism. The Benicàssim area (Maestrat Basin, eastern Spain) constitutes an excellent field analogue for fault-controlled stratabound hydrothermal dolomitization: dolostone geobodies are well exposed and extend over several kilometres away from seismic-scale faults. This work investigates the main controls on the formation of stratabound versus massive dolomitization in carbonate sequences by means of two-dimensional (2D) reactive transport models applied to the Benicàssim case study. Simulation results suggest that the dolomitization capacity of Mg-rich fluids reaches a maximum at temperatures around 100 °C and a minimum at 25 °C (studied temperature range: 25–150 °C). It takes of the order of hundreds of thousands to millions of years to completely dolomitize kilometre-long limestone sections, with solutions flowing laterally through strata at velocities of metres per year (m/a). Permeability differences of two orders of magnitude between layers are required to form stratabound dolomitization. The kilometre-long stratabound dolostone geobodies of Benicàssim must have formed under a regime of lateral flux greater than metres per year over about a million years. As long-term dolomitization tends to produce massive dolostone bodies not seen at Benicàssim, the dolomitizing process there must have been limited by the availability of fluid volume or the flow-driving mechanism. Reactive transport simulations have proven a useful tool to quantify aspects of the Benicàssim genetic model of hydrothermal dolomitization.