julilili42/papers huggingface dataset:
An inverse-modelling approach for frequency response correction of capacitive humidity sensors in ABL research with small remotely piloted aircraft (RPA)
2014-09-22

Abstract. The measurement of water vapour concentration in the atmosphere is an ongoing challenge in environmental research. Satisfactory solutions exist for ground-based meteorological stations and measurements of mean values. However, carrying out advanced research of thermodynamic processes aloft as well, above the surface layer and especially in the atmospheric boundary layer (ABL), requires the resolution of small-scale turbulence. Sophisticated optical instruments are used in airborne meteorology with manned aircraft to achieve the necessary fast-response measurements of the order of 10 Hz (e.g. LiCor 7500). Since these instruments are too large and heavy for the application on small remotely piloted aircraft (RPA), a method is presented in this study that enhances small capacitive humidity sensors to be able to resolve turbulent eddies of the order of 10 m. The sensor examined here is a polymer-based sensor of the type P14-Rapid, by the Swiss company Innovative Sensor Technologies (IST) AG, with a surface area of less than 10 mm2 and a negligible weight. A physical and dynamical model of this sensor is described and then inverted in order to restore original water vapour fluctuations from sensor measurements. Examples of flight measurements show how the method can be used to correct vertical profiles and resolve turbulence spectra up to about 3 Hz. At an airspeed of 25 m s−1 this corresponds to a spatial resolution of less than 10 m.
The stability region of the Streptomyces lividans plasmid pIJ101 encodes a DNA-binding protein recognizing a highly conserved short palindromic sequence motif
2014-09-22

Conjugation is a driving force in the evolution and shaping of bacterial genomes. In antibiotic producing streptomycetes even small plasmids replicating via the rolling-circle mechanism are conjugative. Although they encode only genes involved in replication and transfer, the molecular function of most plasmid encoded proteins is unknown. In this work we show that the conjugative plasmid pIJ101 encodes an overlooked protein, SpdA2. We show that SpdA2 is a DNA binding protein which specifically recognizes a palindromic DNA sequence (sps). sps is localized within the spdA2 coding region and highly conserved in many Streptomyces plasmids. Elimination of the palindrome or deletion of spdA2 in plasmid pIJ303 did not interfere with conjugative plasmid transfer or pock formation, but affected segregational stability.
Gene-expression profiling elucidates molecular signaling networks that can be therapeutically targeted in vestibular schwannoma
2014-09-23

Object Vestibular schwannomas (VS) are common benign tumors of the vestibular nerve that cause significant morbidity. The current treatment strategies for VS include surgery or radiation, with each treatment option having associated complications and side effects. The transcriptional landscape of schwannoma remains largely unknown. Methods In this study the authors performed gene-expression profiling of 49 schwannomas and 7 normal control vestibular nerves to identify tumor-specific gene-expression patterns. They also interrogated whether schwannomas comprise several molecular subtypes using several transcription-based clustering strategies. The authors also performed in vitro experiments testing therapeutic inhibitors of over-activated pathways in a schwannoma cell line, namely the PI3K/AKT/mTOR pathway. Results The authors identified over 4000 differentially expressed genes between controls and schwannomas with network analysis, uncovering proliferation and anti-apoptotic pathways previously not implicated in VS. Furthermore, using several distinct clustering technologies, they could not reproducibly identify distinct VS subtypes or significant differences between sporadic and germline NF2–associated schwannomas, suggesting that they are highly similar entities. The authors identified overexpression of PI3K/AKT/mTOR signaling networks in their geneexpression study and evaluated this pathway for therapeutic targeting. Testing the compounds BEZ235 and PKI-587, both novel dual inhibitors of PI3K and mTOR, attenuated tumor growth in a preclinical cell line model of schwannoma (HEI-293). In vitro findings demonstrated that pharmacological inhibition of the PI3K/AKT/mTOR pathway with next-generation compounds led to decreased cell viability and increased cell death. Conclusions These findings implicate aberrant activation of the PI3K/AKT/mTOR pathway as a molecular mechanism of pathogenesis in VS and suggest inhibition of this pathway as a potential treatment strategy.
Impact of Measurement Parameters on Apparent Diffusion Coefficient Quantification in Diffusion-Weighted-Magnetic Resonance Imaging
2014-09-23

The scope of this work was to systematically evaluate the reproducibility of diffusion-weighted imaging and the impact of b values used for apparent diffusion coefficient (ADC) calculation as well as the echo time (TE) on the resulting ADC in phantom studies. We attempted to find a minimum upper b value needed for reliable ADC measurements. In addition, we were able to investigate these impacts not only for different diffusivities but also for different T2 relaxation times. The influence of different b values on ADC calculations for different organs was also assessed in a volunteer study.Diffusion-weighted imaging of a phantom consisting of 16 compartments with combinations of 4 different diffusivities and 4 different T2 relaxation times was conducted 5 times using 11 b values (0-1000 s/mm) and 5 different TEs. Apparent diffusion coefficient was calculated from the 16 compartment regions of interest using 42 different combinations of b values. Reproducibility of ADC was assessed from the coefficient of variation of the 5 measurements. The ADC stability was determined from a voxel-based coefficient of variation (CVsta) and the signal-to-noise ratio (SNR) to find the minimum upper b values for a reliable ADC quantification. The influence of TE on ADC quantification was assessed for 9 different b value combinations. The influence of 9 different b value combinations on ADC was evaluated by a region of interest analysis of 7 organs in 12 volunteers.The found coefficient of variation was between 10.2% and 1.4%, decreasing with increasing upper b value and increasing diffusivities. Accordingly, CVsta and SNR showed the same trend. Using an upper b value of 600 s/mm gives already reliable ADC results showing a maximum CVsta of 7.5%, whereas an upper b value of 1000 s/mm revealed a maximum CVsta of 5.5%. Values of ADC reduced with increasing upper b value in phantom as well as in human data. Apparent diffusion coefficient also reduced with increasing TE and tended to increase for increasing T2 relaxation times and increasing diffusion restriction.Apparent diffusion coefficient can be measured with high reproducibility but strongly depends on b values used and TE, which should be kept constant in each examination protocol. Whereas upper b values as low as 400 s/mm can be used for examinations of tissues with low diffusivities, very high b values (>1000 s/mm) are needed to reach an optimal SNR for high diffusive tissues. An upper b value of 600 s/mm is a good compromise regarding ADC stability, SNR, and measurement time for all tissue types.
What May I Hope? Why It Can Be Rational to Rely on One's Hope
2014-09-23

In hoping, what is important to us seems possible, which makes our life appear meaningful and motivates us to do everything within our reach to bring about the things that we hope for. I argue that it can be rational to rely on one’s hope: hope can deceive us, but it can also represent things correctly to us. I start with Philip Pettit’s view that hope is a cognitive resolve. I reject this view and suggest instead that hope is an emotion: hope is a felt evaluation for which we can define a corresponding character trait which in its turn qualifies as a virtue if it is felt whenever its correctness conditions are satisfied. For religious hope in particular it follows from my analysis that, if I believe, I may hope.
Successful use of eculizumab for treatment of an acute hemolytic reaction after ABO‐incompatible red blood cell transfusion
2014-09-23

Background Transfusion of ABO major–incompatible red blood cells ( RBCs ) can activate the complement system and can cause severe and even lethal acute hemolytic reactions. The activation of the complement system with formation of C 3a and C 5a (anaphylatoxins) and the release of hemoglobin from the lysed RBCs are thought to mediate clinical signs like fever, hypotension, pain, and acute renal failure. Therapeutic inhibition of the complement cascade in case of ABO ‐incompatible RBC transfusion would be desirable to ameliorate the signs and symptoms and to improve the outcome of the reaction. Study Design and Methods A patient with blood group B was erroneously transfused with a unit of group A 2 RBCs . Within 1 hour after transfusion she received eculizumab, a monoclonal antibody that binds to the complement component C 5 and blocks its cleavage. Clinical and immunohematologic observations are reported here. Results Hemoglobinemia and hemoglobinuria were present for several hours after transfusion, but she developed no hypotension, no renal failure, and no disseminated intravascular coagulation. As shown by flow cytometry, group A cells survived in the peripheral blood for more than 75 days. No immunoglobulin G was detectable by column agglutination technique on these cells. Conclusion A low isoagglutinin titer and blood group A 2 of the erroneously transfused cells most likely were the reason for the absence of clinical signs during and immediately after the ABO ‐incompatible transfusion. In the further course, eculizumab successfully protected the incompatible RBCs from hemolysis for several weeks.
Construction and assessment of individualized proteogenomic databases for large‐scale analysis of nonsynonymous single nucleotide variants
2014-09-23

Next‐generation sequencing projects focusing on genomes and transcriptomes identify millions of single nucleotide variants (SNVs), many of which result in single amino acid substitutions. These nonsynonymous (ns) SNVs are typically not incorporated into protein sequence databases used to identify MS/MS data. Here, we perform a comparative analysis of the assembly of nsSNV‐containing proteogenomic databases. We use a comprehensive transcriptome and proteome dataset of HeLa cells from the literature to derive and to incorporate SNVs into databases applicable to proteomics search engines, and to assess their performance in the identification of nsSNVs. We assemble the databases by (1) translation of SNV‐containing transcripts into all possible reading frames, (2) translation of predicted reading frame, (3) prediction of nsSNVs and subsequent incorporation into canonical protein sequences. We show substantial differences between generated databases in terms of represented nsSNVs and theoretical search space, affecting sensitivity and specificity of database search. We query the databases with &gt;2.2M high‐resolution MS/MS spectra using MaxQuant software and identify 451 variant peptides, containing 401 nsSNVs. We conclude that prediction of reading frame and, if applicable, SNV effect result in comprehensive yet compact databases necessary to retain sensitivity in large‐scale analysis of nsSNVs called from transcriptomics data.
CUX1: a modulator of tumour aggressiveness in pancreatic neuroendocrine neoplasms
2014-09-23

Pancreatic neuroendocrine neoplasms (PNENs) constitute a rare tumour entity, and prognosis and treatment options depend on tumour-mediating hallmarks such as angiogenesis, proliferation rate and resistance to apoptosis. The molecular pathways that determine the malignant phenotype are still insufficiently understood and this has limited the use of effective combination therapies in the past. In this study, we aimed to characterise the effect of the oncogenic transcription factor Cut homeobox 1 ( CUX1 ) on proliferation, resistance to apoptosis and angiogenesis in murine and human PNENs. The expression and function of CUX1 were analysed using knockdown and overexpression strategies in Ins-1 and Bon-1 cells, xenograft models and a genetically engineered mouse model of insulinoma (RIP1Tag2). Regulation of angiogenesis was assessed using RNA profiling and functional tube-formation assays in HMEC-1 cells. Finally, CUX1 expression was assessed in a tissue microarray of 59 human insulinomas and correlated with clinicopathological data. CUX1 expression was upregulated during tumour progression in a time- and stage-dependent manner in the RIP1Tag2 model, and associated with pro-invasive and metastatic features of human insulinomas. Endogenous and recombinant CUX1 expression increased tumour cell proliferation, tumour growth, resistance to apoptosis, and angiogenesis in vitro and in vivo . Mechanistically, the pro-angiogenic effect of CUX1 was mediated via upregulation of effectors such as HIF1α and MMP9. CUX1 mediates an invasive pro-angiogenic phenotype and is associated with malignant behaviour in human insulinomas.
The Feeling of Religious Longing and Passionate Rationality
2014-09-23

What is the feeling of religious longing and how, if at all, can religious longing justify religious beliefs? Starting with an analogy between religious longing and basic physical needs and an analogy between religious longing and musical longing, I argue that the feeling of religious longing is characterized by four features: (1) its generality, (2) its indeterminate transcendent object which by its nature is not capable of empirical verification or falsification, (3) its mode of being infinitely interested in passion and (4) its ambiguity with regard to our own power and powerlessness. Religious longing can neither epistemically nor pragmatically justify religious beliefs. If we want to account for the rationality of religious beliefs motivated by religious longing, we have to consider passionate rationality as a third kind of rationality. We wholeheartedly take as true what we experience as a condition of the possibility of (an understandable, meaningful) life.
285 * NANOLIPOSOMAL-MEDIATED SIRNA TARGETING OF EA.HY926: A PROMISING DELIVERY METHOD
2014-09-23

Objectives: Gene silencing with therapeutic small interfering ribonucleic acids (siRNA) is a promising treatment strategy for non-small-cell lung carcinoma. The main goal of this study was to develop a nanoliposomal delivery system with enhanced transfection efficiency of siRNA to overcome their insufficient cellular delivery in human endothelial cells and non-small-cell lung carcinoma cells. Methods: The liposomes were composed of a liposomal transfection reagent (DOTAP), a fusogenic lipid (DOPE) and a PEGylated lipid (DSPE-PEG2000). As a first model system, human endothelial cells (Ea.hy926) were plated and following overnight growth, nanoliposomal-siRNA complex containing ICAM-1 siRNA (100 nM) or scrambled-siRNA as a negative control, was added in different concentrations (10, 50 and 100 μM). After transfection and activation of the ICAM-1 siRNA with inflammatory cytokine tumour necrosis factor (TNF-α) we marked the human endothelial cells with the CD54E antibody and used fluorescence-activated cell sorting (FACS) for the analysis. Cell viability was analysed with CASY technology. Results: The results of the silencing potency differed in each concentration of the nanoliposomal complex used. Significant reductions of protein expression were achieved by all ICAM-1 siRNA complexes, the most significant by the 50 μM complex with a mean reduction level of 65.18%. The cell viability was not changed. Conclusion: We demonstrated that using optimal nanoliposomal complexes for effective human endothelial cell (Ea.hy926) targeting leads to high transfection efficiency and significant suppression of the protein level. Overcoming the siRNA extracellular instability with cell viability being unchanged shows that the developed delivery system may become a promising therapeutic strategy for non-small-cell lung carcinoma.
Intentional Emotions and Knowledge about God
2014-09-23

Some recent theories of emotion propose that emotions are perceptions of value laden situations and thus provide us with epistemic access to values. In this paper I take up Mark Wynn’s application of this theory to religious experience and try to argue that his McDowell-inspired account of intentional emotions leads to limitations for the justificatory force of religious experiences and to difficult questions about the metaphysical status of the object of religious experiences: if emotions and religious experiences are largely similar, then, just as emotions, religious experiences cannot justify beliefs about the existence of objects, but merely beliefs about certain qualities they might have. Also, if emotions and religious experiences are largely similar, then, just as the objects of emotions, the object of religious experience turns out to be essentially mind-dependent.
International Charter of principles for sharing bio-specimens and data
2014-09-24

There is a growing international agreement on the need to provide greater access to research data and bio-specimen collections to optimize their long-term value and exploit their potential for health discovery and validation. This is especially evident for rare disease research. Currently, the rising value of data and bio-specimen collections does not correspond with an equal increase in data/sample-sharing and data/sample access. Contradictory legal and ethical frameworks across national borders are obstacles to effective sharing: more specifically, the absence of an integrated model proves to be a major logistical obstruction. The Charter intends to amend the obstacle by providing both the ethical foundations on which data sharing should be based, as well as a general Material and Data Transfer Agreement (MTA/DTA). This Charter is the result of a careful negotiation of different stakeholders' interest and is built on earlier consensus documents and position statements, which provided the general international legal framework. Further to this, the Charter provides tools that may help accelerate sharing. The Charter has been formulated to serve as an enabling tool for effective and transparent data and bio-specimen sharing and the general MTA/DTA constitutes a mechanism to ensure uniformity of access across projects and countries, and may be regarded as a consistent basic agreement for addressing data and material sharing globally. The Charter is forward looking in terms of emerging issues from the perspective of a multi-stakeholder group, and where possible, provides strategies that may address these issues.
Reimbursement for reconstruction by tissue transfer–a European comparison
2014-09-24

Most countries have procedure-driven payment systems for flap surgery, which additionally can strongly depend on the diagnosis. Nevertheless the latter does not always justify existing price differences. For the first time, clinical cases in tissue transfer were compared internationally. In today`s dynamic world of health care, we should observe other countries` compensation systems to identify ways of improving our own.
Sequence co-evolution gives 3D contacts and structures of protein complexes
2014-09-25

Protein–protein interactions are fundamental to many biological processes. Experimental screens have identified tens of thousands of interactions, and structural biology has provided detailed functional insight for select 3D protein complexes. An alternative rich source of information about protein interactions is the evolutionary sequence record. Building on earlier work, we show that analysis of correlated evolutionary sequence changes across proteins identifies residues that are close in space with sufficient accuracy to determine the three-dimensional structure of the protein complexes. We evaluate prediction performance in blinded tests on 76 complexes of known 3D structure, predict protein–protein contacts in 32 complexes of unknown structure, and demonstrate how evolutionary couplings can be used to distinguish between interacting and non-interacting protein pairs in a large complex. With the current growth of sequences, we expect that the method can be generalized to genome-wide elucidation of protein–protein interaction networks and used for interaction predictions at residue resolution.
Predicting career aspirations and university majors from academic ability and self-concept
2014-09-25

Science, technology, engineering, and mathematics university majors are critical pathways toward prestigious careers, yet women are still underrepresented in many of these domains. In this chapter, we review the role that self-beliefs play in the development of educational aspirations and attempts to realize those aspirations at the end of secondary school. In particular, we use the internal/external frame of reference model to explore the potential of achievement and self-concept profiles as predictors of university major aspirations and attainment as one possible explanation for gender differences in these domains. After reviewing previous research in this area, we provide a research example using a large longitudinal database from Germany (N = 1,881). Results suggest that (a) high math achievement and self-concept predicted math-intensive university major choice and lower likelihood of entering verbal-intensive majors (and vice versa); (b) there appeared to be a continuum of university majors such that strong mathematics achievement and self-concept profiles predicted entry into hard sciences, while the opposite profile predicted entry into the humanities with biology and medicine displaying more mixed patterns; and (c) after controlling for achievement and self-concept there were still important gender differences in university majors. Implications for theory and practice are discussed.
Effect of Sample Slope on Image Formation in Scanning Ion Conductance Microscopy
2014-09-25

Scanning ion conductance microscopy (SICM) is a scanning probe technique that allows investigating surfaces of complex, convoluted samples such as living cells with minimal impairment. This technique monitors the ionic current through the small opening of an electrolyte-filled micro- or nanopipet that is approached toward a sample, submerged in an electrolyte. The conductance drops in a strongly distance-dependent manner. For SICM imaging, the assumption is made that positions of equal conductance changes correspond to equal tip-sample distances and thus can be utilized to reconstruct the sample surface. Here, we examined this assumption by investigating experimental approach curves toward silicone droplets, as well as finite element modeling of the imaging process. We found that the assumption is strictly true only for perpendicular approaches toward a horizontal sample and otherwise overestimates the sample height by up to several pipet opening radii. We developed a method to correct this overestimation and applied it to correct images of fixed cellular structures and living entire cells.
Preclinical Evaluation of the Thrombogenicity and Endothelialization of Bare Metal and Surface-Coated Neurovascular Stents
2014-09-25

Albumin and heparin coatings clearly improve the thrombogenicity of the stents and thus may represent fundamental progress in the treatment of intracranial aneurysms. Moreover, preclinical evaluation of neurovascular stents under physiologic conditions supports and accelerates the development of more biocompatible neurovascular stents.