julilili42/papers huggingface dataset:
ROS1 gene rearrangement and expression of splice isoforms in lung cancer, diagnosed by a novel quantitative RT-PCR assay
2016-07-07

Successful treatment of lung cancer (NSCLC) patients with ROS1 inhibitors depends on the accurate diagnosis of ROS1 gene rearrangements. The approved FISH tests are low-throughput assays difficult to use in daily diagnostic practice. Immunohistochemistry is currently discussed as screening test. We aimed to devise an alternative, sensitive diagnostic test for the rearrangement of ROS1 and to investigate upregulated ROS1 gene expression as potential target in NSCLC. We developed a qRT-PCR assay adapted to RNA isolated from FFPE material and applied it to 695 NSCLC specimens. The reliability to detect ROS1 rearrangements was evidenced by comparison with FISH and immunohistochemistry. qRT-PCR analysis detected unbalanced ROS1 expression indicative of gene rearrangement in 5 (0.7%) and expression of non-rearranged ROS1 transcripts in 65 (9.6%) of 680 interpretable tumors. In comparison with FISH, qRT-PCR accurately typed 99% of 5 rearranged and 121 non-rearranged tumors. Immunohistochemistry detected ROS1 protein expression in 7/8 tumors with gene fusions and 6/35 NSCLC with transcriptional upregulation. To elucidate RNA processing, 12 NSCLC were examined by systematic RT-PCR and sequence analysis. In all 12 NSCLC analyzed, up-regulated gene expression independent of translocation was associated with aberrant expression of fetal transcript isoforms identified here. We conclude that our qRT-PCR assay reliably diagnoses and distinguishes ROS1 rearrangements and expression of non-rearranged transcripts. Immunostaining is a suitable screening tool, but re-examination of ROS1 protein expressing cases by qRT-PCR/FISH is compulsory. The expression of ROS1 splice isoforms – shown here for the first time - may be relevant for ROS1 inhibitor therapy in NSCLC.
Calcium dynamics change in degenerating cone photoreceptors
2016-07-08

Cone photoreceptors (cones) are essential for high-resolution daylight vision and colour perception. Loss of cones in hereditary retinal diseases has a dramatic impact on human vision. The mechanisms underlying cone death are poorly understood, and consequently, there are no treatments available. Previous studies suggest a central role for calcium (Ca<sup>2+</sup>) homeostasis deficits in photoreceptor degeneration; however, direct evidence for this is scarce and physiological measurements of Ca<sup>2+ </sup>in degenerating mammalian cones are lacking.Here, we took advantage of the transgenic HR2.1:TN-XL mouse line that expresses a genetically encoded Ca<sup>2+ </sup>biosensor exclusively in cones. We cross-bred this line with mouse models for primary ("cone photoreceptor function loss-1", cpfl1) and secondary ("retinal degeneration-1", rd1) cone degeneration, respectively, and assessed resting Ca<sup>2+ </sup>levels and light-evoked Ca<sup>2+ </sup>responses in cones using two-photon imaging. We found that Ca<sup>2+ </sup>dynamics were altered in cpfl1 cones, showing higher noise and variable Ca<sup>2+ </sup>levels, with significantly wider distribution than for wild-type and rd1 cones. Unexpectedly, up to 21% of cpfl1 cones still displayed light-evoked Ca<sup>2+ </sup>responses, which were larger and slower than wild-type responses. In contrast, genetically intact rd1 cones were characterized by lower noise and complete lack of visual function.Our study demonstrates alterations in cone Ca<sup>2+ </sup>dynamics in both primary and secondary cone degeneration. Our results are consistent with the view that higher (fluctuating) cone Ca<sup>2+ </sup>levels are involved in photoreceptor cell death in primary (cpfl1) but not in secondary (rd1) cone degeneration. These findings may guide the future development of therapies targeting photoreceptor Ca<sup>2+ </sup>homeostasis.
Direct Comparison of Second Harmonic Generation and Two-Photon Photoluminescence from Single Connected Gold Nanodimers
2016-07-08

In this article we compare the two-photon photoluminescence and second harmonic generation from single connected gold nanodimers. Analyzing the particle size-dependent nonlinear optical spectra and performing excitation polarization resolved measurements using an experimental setup combining a femtosecond laser source with a parabolic mirror, we show that second harmonic generation and two-photon photoluminescence have different behaviors despite the same expected fundamental intensity-dependence. For further understanding of the observed phenomena, the plasmon resonances of single nanodimers are investigated using dark-field optical microscopy, and calculations are performed with Green's tensor method. Furthermore, the underlying mechanisms explaining the differences between these two optical processes are investigated using a surface integral equation method for the nonlinear computations. This study reveals that the different trends in the polarization-dependences of two-photon photoluminescence and second harmonic generation with the increasing diameters of the connected discs are due to their distinct physical nature, resulting in specific rules for plasmon enhancement and different coherence properties. Furthermore, this article clearly points out that special care has to be taken when two-photon photoluminescence and second harmonic generation are used to evaluate the amplitudes of electromagnetic hot-spots generated in plasmonic nanostructures.
Limits on Momentum-Dependent Asymmetric Dark Matter with CRESST-II
2016-07-08

The usual assumption in direct dark matter searches is to consider only the spin-dependent or spin-independent scattering of dark matter particles. However, especially in models with light dark matter particles O(GeV/c^{2}), operators which carry additional powers of the momentum transfer q^{2} can become dominant. One such model based on asymmetric dark matter has been invoked to overcome discrepancies in helioseismology and an indication was found for a particle with a preferred mass of 3 GeV/c^{2} and a cross section of 10^{-37} cm^{2}. Recent data from the CRESST-II experiment, which uses cryogenic detectors based on CaWO_{4} to search for nuclear recoils induced by dark matter particles, are used to constrain these momentum-dependent models. The low energy threshold of 307 eV for nuclear recoils of the detector used, allows us to rule out the proposed best fit value above.
Expression of 4-1Bb and Its Ligand on Blasts Correlates with Prognosis of Patients with Aml
2016-07-08

Costimulatory ligands (COLs) and their receptors (COR) regulate immune reactions and cellular survival and might be relevant in acute myeloid leukemia (AML). This study evaluated the clinical relevance of 4-1BBL, glucocorticoid-induced TNFR-related protein (GITR) and ligand (GITRL), CD80, and CD86 in case of expression on AML blasts. 98 patients were evaluated at initial diagnosis. Immunophenotypically evaluated specific fluorescence index (SFI) levels of COR and COL on blasts were correlated with morphological, cytogenetic, and several prognostic parameters. Significantly higher COR expression was seen in monocytic versus non-monocytic AML subtypes; GITR, p=0.05; GITRL, p=0.005; CD86, p=0.001). Cut-off values for two COR and their ligands were evaluated: cases presenting with 4-1BB values above cut-off 1.2 SFI levels correlated (tendentially) significantly with a higher probability for disease-free survival (DFS, p=0.06) and a favorable HR of 0.2; p=0.04 for relapse. HR for death was also significantly lower in this group (0.12; p=0.04). In contrast, a lower probability for DFS and overall survival was seen in cases with 4-1BBL expression above 2.2 SFI levels (p=0.08 and p=0.09). In addition, multivariate analysis showed a significantly higher probability of death in this group (HR 10.3, p=0.04). Expression of CD80 and CD86 did not show significant prognostic relevance. On initial diagnosis, 4-1BB and 4-1BBL qualify as markers for prediction of patients’ course and represent a valuable screening target for patients with AML at initial diagnosis.
Cell wall glycopolymers of Firmicutes and their role as nonprotein adhesins
2016-07-11

Cell wall glycopolymers ( CWG s) of gram‐positive bacteria have gained increasing interest with respect to their role in colonization and infection. In most gram‐positive pathogens they constitute a large fraction of the cell wall biomass and represent major cell envelope determinants. Depending on their chemical structure they modulate interaction with complement factors and play roles in immune evasion or serve as nonprotein adhesins that mediate, especially under dynamic conditions, attachment to different host cell types. In particular, covalently peptidoglycan‐attached CWG s that extend well above the cell wall seem to interact with glyco‐receptors on host cell surfaces. For example, in the case of Staphylococcus aureus, the cell wall‐attached teichoic acid ( WTA ) has been identified as a major CWG adhesin. A recent report indicates that a type‐F scavenger receptor, termed SR ‐F1 ( SREC ‐I), is the predominant WTA receptor in the nasal cavity and that WTA – SREC ‐I interaction plays an important role in S. aureus nasal colonization. Therefore, understanding the role of CWG s in complex processes that mediate colonization and infection will allow novel insights into the mechanisms of host–microbiota interaction.
An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression
2016-07-11

Breast cancer is the most diagnosed malignancy and the second leading cause of cancer mortality in females. Previous association studies have identified variants on 2q35 associated with the risk of breast cancer. To identify functional susceptibility loci for breast cancer, we interrogated the 2q35 gene desert for chromatin architecture and functional variation correlated with gene expression. We report a novel intergenic breast cancer risk locus containing an enhancer copy number variation (enCNV; deletion) located approximately 400Kb upstream to IGFBP5, which overlaps an intergenic ERα-bound enhancer that loops to the IGFBP5 promoter. The enCNV is correlated with modified ERα binding and monoallelic-repression of IGFBP5 following oestrogen treatment. We investigated the association of enCNV genotype with breast cancer in 1,182 cases and 1,362 controls, and replicate our findings in an independent set of 62,533 cases and 60,966 controls from 41 case control studies and 11 GWAS. We report a dose-dependent inverse association of 2q35 enCNV genotype (percopy OR = 0.68 95%CI 0.55-0.83, P = 0.0002; replication OR = 0.77 95% CI 0.73-0.82, P = 2.1 × 10-19) and identify 13 additional linked variants (r2 &gt; 0.8) in the 20Kb linkage block containing the enCNV (P = 3.2 × 10-15 - 5.6 × 10-17). These associations were independent of previously reported 2q35 variants, rs13387042/rs4442975 and rs16857609, and were stronger for ER-positive than ER-negative disease. Together, these results suggest that 2q35 breast cancer risk loci may be mediating their effect through IGFBP5.
Dynamics of a spinning particle in a linear in spin Hamiltonian approximation
2016-07-11

We investigate for order and chaos the dynamical system of a spinning test\\nparticle of mass moving in the spacetime background of a Kerr black hole of\\nmass M. This system is approximated in our investigation by the linear in spin\\nHamiltonian function provided in [E. Barausse, and A. Buonanno, Phys.Rev. D 81,\\n084024 (2010)]. We study the corresponding phase space by using 2D projections\\non a surface of section and the method of color and rotation on a 4D Poincar\\\\'e\\nsection. Various topological structures coming from the non-integrability of\\nthe linear in spin Hamiltonian are found and discussed. Moreover, an\\ninteresting result is that from the value of the dimensionless spin of the particle and below, the impact of the non-integrability of\\nthe system on the motion of the particle seems to be negligible.\\n
Competitive Balance and Attention Level Effects: Theoretical Considerations and Preliminary Evidence
2016-07-11

We try to better understand possible reasons for deviations between statistically-measured competitive balance (CB) and perceived CB.Moreover, we suggest answers to the following questions: are there specific dimensions of CB that are perceived to be significantly less balanced in the Danish Superligaen compared to the other two leagues?Are there objective measures that "confirm" the fans' perception or does OCB in general deviate from PCB?
Athena Wide Field Imager key science drivers
2016-07-11

The Wide Field Imager (WFI) is one of two instruments for the Advanced Telescope for High-ENergy Astrophysics (Athena). In this paper we summarise three of the many key science objectives for the WFI – the formation and growth of supermassive black holes, non-gravitational heating in clusters of galaxies, and spin measurements of stellar mass black holes – and describe their translation into the science requirements and ultimately instrument requirements. The WFI will be designed to provide excellent point source sensitivity and grasp for performing wide area surveys, surface brightness sensitivity, survey power, and absolute temperature and density calibration for in-depth studies of the outskirts of nearby clusters of galaxies and very good high-count rate capability, throughput, and low pile-up, paired with very good spectral resolution, for detailed explorations of bright Galactic compact objects.
Strain localisation and dynamic recrystallisation in the ice-air aggregate: A numerical study
2016-07-11

Abstract. We performed numerical simulations on the micro-dynamics of ice with air inclusions as a second phase. This provides first results of a numerical approach to model dynamic recrystallisation in polyphase crystalline aggregates. Our aim was to investigate the rheological effects of air inclusions and explain the onset of dynamic recrystallisation in the permeable firn. The simulations employ a full field theory crystal plasticity code coupled to codes simulating dynamic recrystallisation processes and predict time-resolved microstructure evolution in terms of lattice orientations, strain distribution, grain sizes and grain boundary network. Results show heterogeneous deformation throughout the simulations and indicate the importance of strain localisation controlled by air inclusions. This strain localisation gives rise to locally increased energies that drive dynamic recrystallisation and induce heterogeneous microstructures that are coherent with natural firn microstructures from EPICA Dronning Maud Land ice coring site in Antarctica. We conclude that although overall strains and stresses in firn are low, strain localisation associated with locally increased strain energies can explain the occurrence of dynamic recrystallisation.
WFI electronics and on-board data processing
2016-07-11

The Wide Field Imager is one of two instruments on-board the future ATHENA X-ray observatory. Its main scientific objective is to perform a sky survey in the energy range of 0.2 keV up to 15 keV with an end-of-life spectral resolution (FWHM) better than 170 eV (at 7 keV) and a frame rate of at least 200 Hz. The field of view will be 40 arcmin squared wherefore a focal plane array with 4 large sensors each with a size of 512 times 512 pixels will be developed. Additionally, a fast detector with a size of 64 times 64 pixels and a frame rate of 12.5 kHz will be implemented in order to enhance the instrument with high count rate detection of bright sources. The data processing electronics within the WFI instrument is distributed over several subsystems: DEPFET sensors sensitive in the x-ray energy regime and front-end electronics are located inside the Camera Head. Data pre-processing inside the Detector Electronics will be performed in an FPGA-based frame-processor. FPGA external memory will be used to store offset and noise maps wherefore memory controllers have to be developed. Fast read and write access to the maps combined with robustness against radiation damage (e.g. bit-flips) has to be ensured by the frame-processor design.
An updated approach to the study of proton propagation in the eROSITA mirror system
2016-07-11

The German telescope eROSITA will be the first X-ray instrument orbiting around the L-2 lagrangian point. Therefore, modelling the radiation environment in that region of space and its interaction with the instrument is particularly important, as no measured data of other X-ray detectors can be used as a reference to predict how the space conditions will impact the instrumental capabilities. The orbit around L-2 extends well beyond the Earth ́s magnetosphere, where the flux of galactic cosmic particles is cut by the geomagnetic field, and fluxes of energetic particles one order of magnitude higher than in low Earth orbits are expected. Furthermore, as experienced by Chandra and XMM-Newton, softer protons may be scattered through the mirror shells and funneled to the focal plane, representing a potential additional source of background. To investigate and assess this component we are developing a ray tracing simulator for protons, that follows the track of each proton from the entrance pupil down to the focal plane. In this paper we report on an updated version of the code that allows to propagate protons in both the polar and azimuthal directions in elastic regime.
Design of Core–Shell Heterostructure Nanofibers with Different Work Function and Their Sensing Properties to Trimethylamine
2016-07-12

The metal oxide semiconductor (MOS) core-shell heterostructure nanofibers (NFs) have been successfully synthesized via an environmentally friendly coaxial electrospinning approach. To demonstrate the potential applications of the as-prepared samples, sensors based on MOS core-shell heterostructure NFs have been fabricated and their gas sensing properties were investigated. Results show that the sensors exhibit an advanced gas sensing property to trimethylamine (TMA) including the outstanding selectivity and rapid response/recovery processes in comparison with the sensors based on single MOS NFs. These phenomena are closely associated with the electron flow caused by the work function difference between MOS of the core and the shell. The approach proposed in this study may contribute to the realization of more sensitive MOS core-shell heterostructure sensors.
Rates of and Experiences with Corneal Donation at the University Hospital Tübingen From 2002 To 2015
2016-07-12

BACKGROUND This study aimed to report the rates and experiences of corneal donation at the University Hospital Tübingen. MATERIAL AND METHODS Data from all cornea donors from January 2002 to December 2015 were analyzed. The rates of corneal donation were examined. From 2002 to 2008, an ophthalmic resident handled the corneal donor procurement in addition to his ward work. From 2009 to 2015, an ophthalmic resident handled the corneal donor procurement on a full-time basis. RESULTS Among the 10 260 deaths, consent for corneal donation was obtained in 892 cases. The mean annual corneal donation rate was 8.7 donors per 100 deaths (range: 2.0-17.8). The mean corneal donation rate in the first period without a full-time ophthalmic resident in the eye bank team was 4.0 donors per 100 deaths (95 % confidence interval [CI]: 1.0-6.9) and in the second period 12.3 donors per 100 deaths (95 % CI: 3.2-21.5) (P<0.0001). Comparing the periods before and after the modification of the eye bank team, the corneal donation rate was increased by more than 3 times. CONCLUSIONS Our study showed the influence of the eye banking team on the corneal donation rate. Modification of the eye bank team, by recruiting a full-time resident at a University Hospital with 1500 beds, increased the corneal donation rate by more than 3 times. It appears necessary to strengthen this team with sufficient staff levels to improve donor rates.
Visual trimorphemic compound recognition in a morphographic script
2016-07-12

This lexical decision with eye-tracking study investigated how Japanese trimorphemic compounds (e.g. 体温計 “clinical thermometer”) are recognised. The questions answered were, in the course of decomposing and composing Japanese trimorphemic compounds, (1) whether recognition processes are tuned for a specific branching direction, (2) whether the morphological processing proceeds in a bottom-up combinatorial manner, and (3) whether the three constituents of trimorphemic compounds are equally important and processed serially. Mixed-effects regression analyses of response times and fixation durations revealed that a left-branching advantage appears in a late time frame and that, although there was early processing of the whole compound from the first fixation, a character frequency effect was also observed. Furthermore, the first and the third, but not the second, constituent frequencies contributed to compound recognition. This bathtub-like effect was further supported by corpus-based evidence: the conditional probability for the second constituent is incomparably high.
A standardized production pipeline for high profile targets fromMycobacterium tuberculosis
2016-07-12

Purpose Tuberculosis is still a major threat to global health. New tools and strategies to produce disease‐related proteins are quintessential for the development of novel vaccines and diagnostic markers. Experimental design To obtain recombinant proteins from Mycobacterium tuberculosis (Mtb) for use in clinical applications, a standardized procedure was developed that includes subcloning, protein expression in Mycobacterium smegmatis and protein purification using chromatography. The potential for the different protein targets to serve as diagnostic markers for tuberculosis was established using multiplex immunoassays. Results Twelve soluble proteins from Mtb, including one protein complex, were purified to near‐homogeneity following recombinant expression in M. smegmatis . Protein purity was assessed both by size exclusion chromatography and MS. Multiplex serological testing of the final protein preparations showed that all but one protein displayed a clear antibody response in serum samples from 278 tuberculosis patients. Conclusion and clinical relevance The established workflow comprises a simple, cost‐effective, and scalable pipeline for production of soluble proteins from Mtb and can be used to prioritize immunogenic proteins suitable for use as diagnostic markers.
Spectrum, radial wave functions, and hyperfine splittings of the Rydberg states in heavy alkali-metal atoms
2016-07-12

We calculate the bound state spectrum of the highly excited valence electron in the heavy alkali atoms solving the radial Schr\\"odinger eigenvalue problem numerically with an accurate spectral collocation algorithm that applies also for a large principal quantum number . As an effective single-particle potential we favor the reputable potential of Marinescu \\emph{et al}., {[}Phys. Rev.A \\textbf{49}, 982(1994){]}. Recent quasiclassical calculations of the quantum defect of the valence electron agree for orbital angular momentum overall remarkably well with the results of the numerical calculations, but for the Rydberg states of rubidium and also cesium with this agreement is less fair. The reason for this anomaly is that the potential acquires for deep inside the ionic core a tiny second classical region, thus invalidating a standard WKB calculation with two widely spaced turning points. Comparing then our numerical solutions of the radial Schr\\"odinger eigenvalue problem with the uniform analytic WKB approximation of Langer we observe everywhere a remarkable agreement, apart from a tiny region around the inner turning point. With help of an ansatz proposed by Fock we obtain for the \\emph{s}-states a second uniform analytic approximation to the radial wave function complementary to the WKB approximation of Langer, which is exact for . The value of the radial \\emph{s}-wave function at is analytically found, thus validating the Fermi-Segr\\`e formula for the magnetic dipole interaction constant .