julilili42/papers huggingface dataset:
Tuning to non‐symbolic proportions in the human frontoparietal cortex
2009-09-24

Abstract Humans share with many species a non‐verbal system to estimate absolute quantity. This sense of number has been linked to the activity of quantity‐selective neurons that respond maximally to preferred numerosities. With functional magnetic resonance imaging adaptation, we now show that populations of neurons in the human parietal and frontal cortex are also capable of encoding quantity ratios, or proportions, using the same non‐verbal analog code as for absolute number. Following adaptation to visually presented constant proportions (specified by the ratio of line lengths or numerosities), we introduced novel relative magnitudes to examine the tuning characteristics of the population of stimulated neurons. In bilateral parietal and frontal cortex we found that blood oxygenation level‐dependent signal recovery from adaptation was a function of numerical distance between the deviant proportion and the adaptation stimulus. The strongest effects were observed in the cortex surrounding the anterior intraparietal sulcus, a region considered pivotal for the processing of absolute magnitudes. Overall, there was substantial overlap of frontoparietal structures representing whole numbers and proportions. The identification of tuning to non‐symbolic ratio stimuli, irrespective of notation, adds to the magnitude system a remarkable level of sophistication by demonstrating automatic access to a composite, derived quantitative measure. Our results argue that abstract concepts of both absolute and relative number are deeply rooted in the primate brain as fundamental determinants of higher‐level numerical cognition.
Biogeochemical and Isotopic Gradients in a BTEX/PAH Contaminant Plume: Model-Based Interpretation of a High-Resolution Field Data Set
2009-09-24

A high spatial resolution data set documenting carbon and sulfur isotope fractionation at a tar oil-contaminated, sulfate-reducing field site was analyzed with a reactive transport model. Within a comprehensive numerical model, the study links the distinctive observed isotope depth profiles with the degradation of various monoaromatic and polycyclic aromatic hydrocarbon compounds (BTEX/PAHs) under sulfate-reducing conditions. In the numerical model, microbial dynamics were simulated explicitly and isotope fractionation was directly linked to the differential microbial uptake of lighter and heavier carbon isotopes during microbial growth. Measured depth profiles from a multilevel sampling well with high spatial resolution served as key constraints for the parametrization of the model simulations. The results of the numerical simulations illustrate particularly well the evolution of the isotope signature of toluene, which is the most rapidly degrading compound and the most important reductant at the site. The resulting depth profiles at the observation well show distinct differences between the small isotopic enrichment in the contaminant plume core and the much stronger enrichment of up to 3.3 per thousand at the plume fringes.
Phosphoinositide 3-kinase γ required for lipopolysaccharide-induced transepithelial neutrophil trafficking in the lung
2009-09-24

Phosphoinositide 3-kinase γ( PI3Kγ ) is a critical mediator of directional cell movement. Here, we sought to characterise the role of PI3Kγ in mediating the different steps of polymorphonuclear leukocyte (PMN) trafficking in the lung. In a murine model of lipopolysaccharide (LPS)-induced lung injury, PMN migration into the different lung compartments was determined in PI3Kγ gene-deficient ( PI3Kγ -/- ) and wild-type mice. Bone marrow chimeras were created to characterise the role of PI3Kγ on haematopoietic versus nonhaematopoietic cells. A small-molecule PI3Kγ inhibitor was tested in vitro and in vivo . PMN adhesion to the pulmonary endothelium and transendothelial migration into the lung interstitium was enhanced in PI3Kγ -/- mice. However, transepithelial migration into the alveolar space was reduced in these mice. When irradiated PI3Kγ -/- mice were reconstituted with bone marrow from wild-type mice, migratory activity into the alveolar space was restored partially. A small-molecule PI3Kγ inhibitor reduced chemokine-induced PMN migration in vitro when PMNs or epithelial cells, but not when endothelial cells, were treated. The inhibitor also reduced LPS-induced PMN migration in vivo . We conclude that PI3Kγ is required for transepithelial but not for transendothelial migration in LPS-induced lung injury. Inhibition of PI3Kγ activity may be effective at curbing excessive PMN infiltration in lung injury.
The Many Faces of Rare Earth Carbodiimide Compounds
2009-09-24

Abstract Solid state metathesis reactions have been established as a successful tool in syntheses of rare earth carbodiimide compounds. Current results evidence the new compounds Li RE (CN 2 ) 2 with RE = La, Ce and the carbodiimide nitride Ce 3 (CN 2 ) 3 N. Li RE (CN 2 ) 2 compounds were synthesized by solid state metathesis reactions between RE F 3 and Li 2 (CN 2 ) in 1:2 molar ratio. Ce 3 (CN 2 ) 3 N was obtained by thermal conversion of LiCe(CN 2 ) 2 ., Crystal structures of LiLa(CN 2 ) 2 and Ce 3 (CN 2 ) 3 N were determined from X‐ray single crystal data (LiLa(CN 2 ) 2 : P 2 1 / m , a = 542.4(2) pm, b = 379.16(7) pm, c = 1013.0(3) pm, β = 101.35(3) °; Ce 3 (CN 2 ) 3 N: P 2 1 2 1 2 1 , a = 672.97(9) pm, b = 1309.8(2) pm, c = 1697.7(3) pm) and LiCe(CN 2 ) 2 was assigned from indexed X‐ray powder diffraction data (LiCe(CN 2 ) 2 : a = 541.9(1) pm, b = 374.50(8) pm, c = 1008.8(2) pm, β = 101.21(1) °)., The crystal structure of LiLa(CN 2 ) 2 represents a layer‐like arrangement of ions as typical for this type of compounds. The crystal structure of Ce 3 (CN 2 ) 3 N reveals chains of [NCe 4 ] tetrahedra running parallel to each other, and trigonal prismatic to trigonal antiprismatic arrangements of six distinctly interconnected [Ce 3 –NCN–Ce 3 ] units. Both structures contain (CN 2 ) 2– ions deviating from their ideal D ∞h symmetry, with C–N distances ranging between 121 and 126 pm and N–C–N angles near 180°.
Probing tensor-vector-scalar theory with gravitational wave asteroseismology
2009-09-24

In order to examine the gravitational waves emitted from the neutron stars in\\nthe tensor-vector-scalar (TeVeS) theory, we derive the perturbation equations\\nfor relativistic stars, where for simplicity we omit the perturbations of\\nvector field. That is, we consider the perturbations of scalar and tensor\\nfields. With this assumption, we find that the axial gravitational waves, which\\nare corresponding to the oscillations of spacetime ( modes), are independent\\nfrom the perturbations of scalar field and the effects of scalar field can be\\nmounted only via the background properties. Using two different equations of\\nstate, we calculate the complex eigenfrequencies of axial modes and find\\nthat the dependences of frequencies on the stellar compactness are almost\\nindependent from the adopted equation of state and the parameter in TeVeS.\\nAdditionally, these dependences of frequencies of axial modes in TeVeS is\\nobviously different from those expected in the general relativity. Thus the\\ndirect observations of gravitational waves could reveal the gravitational\\ntheory in the strong-field regime.\\n
Detection of Gamma Rays from a Starburst Galaxy
2009-09-25

Cosmic Acceleration Cosmic rays are thought to be accelerated in the shock waves produced by supernova explosions and can generate gamma rays when they interact with interstellar particles and radiation. Starburst galaxies, with their increased star formation rates, increased stellar explosion rates, and high densities of gas and radiation fields, are considered to be promising sources of gamma-ray emission. Using the High Energy Stereoscopic System (H.E.S.S) array of telescopes, Acero et al. (p. 1080 , published online 24 September) report the detection of gamma rays from one of the closest starburst galaxies, NGC 253. NGC 253 is a spiral galaxy, similar to our own Galaxy, except that its nucleus is undergoing an episode of intense star formation. The H.E.S.S. findings confirm that cosmic-ray acceleration is indeed efficient in starburst galaxies and open up new ways to understand cosmic-ray acceleration.
Future perspectives for insulinotropic agents in the treatment of type 2 diabetes–DPP‐4 inhibitors and sulphonylureas
2009-09-25

The introduction of dipeptidyl‐peptidase IV inhibitors (DPP‐4 inhibitors) brought a novel class of insulinotropic agents into the treatment options for type 2 diabetes. This paper compares the actions, clinical efficacy and safety of sulphonylureas with those of the DPP‐4 inhibitors. First, the mode of action of both classes of antidiabetic agents is described. Then clinical studies for both substances in monotherapy and combination therapies are compared concerning their effects on glycaemic parameters and long‐term duration of action. Hypoglycaemia incidence and other adverse effects are compared and data on cardiovascular parameters and endpoints are summarized. The effects of sulphonylureas and DPP‐4 inhibitors on beta‐cell function and beta‐cell mass are highlighted. The present and future indications for both sulphonylureas and DPP‐4 inhibitors are discussed.
2-(4-Fluorophenyl)-3-(4-pyridyl)pyrido[2,3-b]pyrazine
2009-09-25

In the crystal structure of the title compound, C(18)H(11)FN(4), the pyridopyrazine system makes dihedral angles of 45.51 (7) and 44.75 (7)° with the attached 4-fluoro-phenyl ring and the pyridine ring, respectively. The 4-fluoro-phenyl ring makes a dihedral angle of 54.54 (8)° with the pyridine ring. The pyridine ring part of the pyridopyrazine ring and the pyrazine ring of two c-glide-plane-related mol-ecules form π-π inter-actions. The angle between the planes is 2.09 (7)° and the distance between the centroids is 3.557 (1)Å.
3-(4-Fluorophenyl)-2-(4-pyridyl)pyrido[2,3-b]pyrazine
2009-09-25

In the crystal structure of the title compound, C(18)H(11)FN(4), the pyridopyrazine ring makes dihedral angles of 34.67 (7) and 52.24 (7)° with the 4-fluoro-phenyl and pyridine rings, respectively. The 4-fluoro-phenyl ring makes a dihedral angle of 59.56 (9)° with the pyridine ring.
N-{4-[3-(4-Fluorophenyl)pyrido[2,3-b]pyrazin-2-yl]-2-pyridyl}isopropylamine
2009-09-25

In the crystal structure of the title compound, C(21)H(18)FN(5), the pyridopyrazine ring system forms dihedral angles of 33.27 (7) and 48.69 (9)° with the 4-fluoro-phenyl and pyridine ring, respectively. The dihedral angle of the 4-fluoro-phenyl and pyridine rings is 57.45 (8)°. The crystal packing is characterized by an inter-molecular N-H⋯N hydrogen bond.
A Point Mutation in the Sensor Histidine Kinase SaeS of Staphylococcus aureus Strain Newman Alters the Response to Biocide Exposure
2009-09-26

ABSTRACT Staphylococcus aureus reacts to changing environmental conditions such as heat, pH, and chemicals through global regulators such as the sae ( S. aureus exoprotein expression) two-component signaling system. Subinhibitory concentrations of some antibiotics were shown to increase virulence factor expression. Here, we investigated the S. aureus stress response to sublethal concentrations of a commonly used biocide (Perform), by real-time quantitative PCR (qRT-PCR), promoter activity assay, sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, and a flow cytometric invasion assay. Perform, acting through the production of reactive oxygen species, generally downregulated expression of extracellular proteins in strains 6850, COL, ISP479C but upregulated these proteins in strain Newman. Upregulated proteins were sae dependent. The Perform component SDS, but not paraquat (another oxygen donor), mimicked the biocide effect. Eap (extracellular adherence protein) was most prominently augmented. Upregulation of eap and sae was confirmed by qRT-PCR. Promoter activity of sae P1 was increased by Perform and SDS. Both substances enhanced cellular invasiveness, by 2.5-fold and 3.2-fold, respectively. Increased invasiveness was dependent on Eap and the sae system, whereas agr , sarA , sigB , and fibronectin-binding proteins had no major effect in strain Newman. This unique response pattern was due to a point mutation in SaeS (the sensor histidine kinase), as demonstrated by allele swapping. Newman saePQRS ISP479C behaved like ISP479C, whereas saePQRS Newman rendered ISP479C equally responsive as Newman. Taken together, the findings indicate that a point mutation in SaeS of strain Newman was responsible for increased expression of Eap upon exposure to sublethal Perform and SDS concentrations, leading to increased Eap-dependent cellular invasiveness. This may be important for understanding the regulation of virulence in S. aureus .
Comorbidity of learning disorders: prevalence and familial transmission
2009-09-28

Background: In order to fully specify the profiles of risk and protective factors of developmental disorders, a better understanding of the conditions under which they co‐occur is required. So far, empirical evidence on comorbidities of specific learning disorders in arithmetic, reading and spelling is scarce. Methods: Prevalence and gender ratios of specific learning disorders in arithmetic (AD), reading (RD), and spelling (SD) and their co‐occurrence were assessed in a large ( N = 2586) population‐based sample of elementary school children and in a subsample of 293 children with at least one learning disorder (LD‐sample). A questionnaire on familial transmission was given to a subsample of 256 parents of children with a learning disorder and 146 typically developing children. Results: The rates of deficits in arithmetic, reading, or spelling were four to five times higher in samples already experiencing marked problems in one academic domain compared to the full population. Thus, comorbidity of learning disorders was confirmed in a fairly standard school population. Rates of co‐occurrence decreased for AD and RD, but not isolated SD when more stringent cutoff criteria were applied, suggesting that the comorbidity of arithmetic and spelling disorder may be more strongly biologically mediated than the comorbidity of arithmetic and reading disorder. We found a preponderance of girls with AD and boys with SD. These imbalanced gender ratios were especially marked for isolated problems, while for comorbid problems gender ratios were mostly balanced with the exception of deficits in arithmetic and reading (but not spelling) which were more typical for girls. The parental questionnaire provided evidence for disorder‐specific familial transmission and co‐segregation of arithmetic and literacy deficits. Conclusions: Comorbidities of learning disorders are not artificial. They are the result of a complex interplay between both general and disorder‐specific aetiological factors.
Direct detection of five common dermatophyte species in clinical samples using a rapid and sensitive 24-h PCR-ELISA technique open to protocol transfer
2009-09-28

Identification of dermatophytes is usually based on morphological characteristics determined by time-consuming microscopic and cultural examinations. An effective PCR-ELISA method has been developed for rapid detection of dermatophyte species directly from clinical specimens within 24 h. Isolated genomic DNA of skin scrapings and nail samples from patients with suspected dermatophyte infections is amplified with species-specific digoxigenin-labelled primers targeting the topoisomerase II gene. The subsequent ELISA procedure with biotin-labelled probes allows a sensitive and specific identification of the five common dermatophytes -Trichophyton rubrum, T. interdigitale, T. violaceum, Microsporum canis and Epidermophyton floccosum. PCR-ELISA, based on the new polyphasic species concept, was assessed using 204 microscopy-positive samples in two university mycological laboratories in Munich and Tübingen, and 316 consecutive specimens - regardless of mycological findings - in a dermatological practice laboratory in Neu-Ulm. One of the five dermatophytes was confirmed by PCR-ELISA in 163 of 204 (79.9%) of the clinical samples from the university hospitals found positive using microscopy. Culture was positive for dermatophytes in 59.8% of the same cases. A significant difference between these two methods could be demonstrated using the McNemar test (P < 0.005). Analysis of specimens from Neu-Ulm confirmed the results in a dermatological practice laboratory as 25.0% of the specimens had positive PCR results, whereas only 7.3% were positive according to culture. Direct DNA isolation from clinical specimens and the PCR-ELISA method employed in this study provide a rapid, reproducible and sensitive tool for detection and discrimination of five major dermatophytes at species level, independent of morphological and biochemical characteristics.
Contrast‐enhanced ultrasound with SonoVue: Differentiation between benign and malignant focal liver lesions in 317 patients
2009-09-29

Abstract Purpose. The aim of the study was to investigate the ability of contrast‐enhanced sonography (CEUS) with the contrast agent SonoVue to differentiate between benign and malignant focal liver lesions. Methods. In a prospective study, we examined 317 patients (204 males, 113 females, aged 59 ± 12 years) with focal liver lesions detected by B‐mode gray‐scale sonography. After intravenous injection of 1.2 mL SonoVue, the liver was examined continuously for 3 minutes using low‐MI sonography with contrast‐specific software. Final diagnosis was established by histopathology, CT, MRI, or HIDA‐scintigraphy. Results. Two hundred nine patients had malignant focal lesions, including 107 hepatocellular carcinomas, 70 metastases, 26 cholangiocellular carcinomas, and 6 other types of malignancy. One hundred eight patients had benign focal lesions, including 30 regenerative nodules, 30 hemangiomas, 13 cases of focal nodular hyperplasia, 12 abscesses, 8 cases of necrosis, 7 cases of focal steatosis areas, and 8 other benign lesions. Hypoenhancement or no enhancement in the late phase was found in 91% of the malignant lesions but in only 37% of the benign lesions ( p &lt; 0.001, sensitivity = 64%, specificity = 93%). Hyperenhancement in the late phase was found in 20% of the benign lesions but in none of the malignant lesions ( p &lt; 0.001, sensitivity = 21%, specificity = 100%). Hyperenhancement in the early phase with diffuse complete enhancement was found in 30% of the patients with malignant lesions but in only 2% of the patients with benign lesions ( p &lt; 0.001, sensitivity = 30%, specificity = 98%). CEUS had a sensitivity of 90%, a specificity of 99%, and an accuracy of 89% in the diagnosis of malignant liver lesions. Conclusion. CEUS is helpful in the differentiation between benign and malignant focal liver lesions. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2010
Small islands and pandemic influenza: Potential benefits and limitations of travel volume reduction as a border control measure
2009-09-29

Abstract Background Some island nations have explicit components of their influenza pandemic plans for providing travel warnings and restricting incoming travellers. But the potential value of such restrictions has not been quantified. Methods We developed a probabilistic model and used parameters from a published model (i.e., InfluSim ) and travel data from Pacific Island Countries and Territories (PICTs). Results The results indicate that of the 17 PICTs with travel data, only six would be likely to escape a major pandemic with a viral strain of relatively low contagiousness (i.e., for R 0 = 1.5) even when imposing very tight travel volume reductions of 99% throughout the course of the pandemic. For a more contagious viral strain ( R 0 = 2.25) only five PICTs would have a probability of over 50% to escape. The total number of travellers during the pandemic must not exceed 115 (for R 0 = 3.0) or 380 (for R 0 = 1.5) if a PICT aims to keep the probability of pandemic arrival below 50%. Conclusion These results suggest that relatively few island nations could successfully rely on intensive travel volume restrictions alone to avoid the arrival of pandemic influenza (or subsequent waves). Therefore most island nations may need to plan for multiple additional interventions (e.g., screening and quarantine) to raise the probability of remaining pandemic free or achieving substantial delay in pandemic arrival.
Rational Design and Synthesis of Potent Dibenzazepine Motifs as β-Secretase Inhibitors
2009-09-29

We have identified small-molecule dibenzazepine inhibitors of beta-secretase (BACE1). These BACE1 inhibitors possess two key salient features. The first is a seven-membered heterocyclic ring fused to two aromatic rings representing the P3-P2 residues. The second is an amide and/or amide bioisostere representing the P1' residue. Rational optimization led to the identification of potent analogues, such as 10 (K(I) = 211 nM).
Effects of Terminal Functional Groups on the Stability of the Polyproline II Structure: A Combined Experimental and Theoretical Study
2009-09-30

The conformational stability of the polyproline II (PPII) helix with respect to the functional groups at the C- and N-termini was examined both experimentally and theoretically. Oligoprolines AcN-[Pro](12)-CONH(2) (1), HN-[Pro](12)-CONH(2) (2), AcN-[Pro](12)-CO(2)H (3), and HN-[Pro](12)-CO(2)H (4) with charged and capped termini served as model compounds, and the relative ease with which they switch from the PPII to the polyproline I (PPI) helix was used as a measure to analyze their conformational stabilities. CD spectroscopic studies demonstrate that a positively charged N-terminus and a negatively charged C-terminus destabilize the PPII helix and favor the PPI helix, whereas capped termini favor the PPII over the PPI helix. These experimental findings are supported by the energy differences between the PPII and PPI helices of oligoprolines 1-4 computed by ab initio methods including electron-correlation effects (second-order Møller-Plesset perturbation theory, MP2). Furthermore, these quantum-chemical calculations show that differences in charge-dipole interactions are responsible for the experimentally and computationally observed relative stabilities. Although these electrostatic interactions between the terminal charges and the amide dipoles stabilize both helices, they are significantly stronger in the PPI helix where the amide bonds are oriented almost linear to the helix axis as compared to the PPII helix in which the amides are nearly perpendicular to the axis. Moreover, we demonstrate that a negative charge at the C-terminus has a more pronounced effect on the relative stability as compared to a positive charge at the N-terminus due to destabilization of the PPII helix by repulsive interaction between the C-terminal carboxylate with the neighboring amide bond. Studies at different pH values verified the electrostatic nature of the observed effects and demonstrate how changes in the protonation state can be used to deliberately stabilize the PPII helix over the PPI helix or vice versa.