julilili42/papers huggingface dataset:
Gastrointestinal absorption and metabolism of hesperetin‐7‐O‐rutinoside and hesperetin‐7‐O‐glucoside in healthy humans
2015-05-27

Scope Hesperetin‐7‐ O ‐rutinoside (hesperidin) reduces blood pressure in healthy volunteers but its intestinal absorption and metabolism are not fully understood. Therefore, we aimed to determine sites of absorption and metabolism of dietary flavanone glycosides in humans. Methods and results Using a single‐blind, randomized crossover design, we perfused equimolar amounts of hesperetin‐7‐ O ‐rutinoside and hesperetin‐7‐ O ‐glucoside directly into the proximal jejunum of healthy volunteers. We assessed the appearance of metabolites in the perfusate, blood and urine, to determine the sites of metabolism and excretion, and compared this to oral administration. The glucoside was rapidly hydrolyzed by brush border enzymes without any contribution from pancreatic, stomach, or other secreted enzymes, or from bacterial enzymes. Only ∼3% of the dose was recovered intact in the perfusate, indicating high absorption. A proportion was effluxed directly back into the perfused segment mainly in the form of hesperetin‐3′‐ O ‐sulfate. In contrast, very little hydrolysis or absorption of hesperetin‐7‐ O ‐rutinoside was observed with ∼80% recovered in the perfusate, no hesperetin metabolites were detected in blood and only traces were excreted in urine. Conclusion The data elucidate the pathways of metabolism of dietary hesperidin in vivo and will facilitate better design of mechanistic studies both in vivo and in vitro.
Prometabolites of 5‐Diphospho‐myo‐inositol Pentakisphosphate
2015-05-27

Abstract Diphospho‐ myo ‐inositol phosphates (PP‐InsP y ) are an important class of cellular messengers. Thus far, no method for the transport of PP‐InsP y into living cells is available. Owing to their high negative charge density, PP‐InsP y will not cross the cell membrane. A strategy to circumvent this issue involves the generation of precursors in which the negative charges are masked with biolabile groups. A PP‐InsP y prometabolite would require twelve to thirteen biolabile groups, which need to be cleaved by cellular enzymes to release the parent molecules. Such densely modified prometabolites of phosphate esters and anhydrides have never been reported to date. This study discloses the synthesis of such agents and an analysis of their metabolism in tissue homogenates by gel electrophoresis. The acetoxybenzyl‐protected system is capable of releasing 5‐PP‐InsP 5 in mammalian cell/tissue homogenates within a few minutes and can be used to release 5‐PP‐InsP 5 inside cells. These molecules will serve as a platform for the development of fundamental tools required to study PP‐InsP y physiology.
Human dignity and the business of business
2015-05-27

Abstract A paradigm change from mechanistic to humanistic management theories and practices is underway, exemplified in a shift from an economics oriented at the fictional homo oeconomicus towards novel models oriented at the real conditio humana. This methodological turn brings about both the opportunity and the necessity of re-orienting management theory as well as business education to the idea of human dignity, as was common in the long-tradition of moral economics from Plato up to Adam Smith. In order to contribute to this theoretical move, in its first part, this paper surveys important conceptions of dignity throughout the ages, and then, in the second part, discusses their implications for a future humanistic business education.
A Multiprotein DNA Translocation Complex Directs Intramycelial Plasmid Spreading during Streptomyces Conjugation
2015-05-27

ABSTRACT Conjugative DNA transfer in mycelial Streptomyces is a unique process involving the transfer of a double-stranded plasmid from the donor into the recipient and the subsequent spreading of the transferred plasmid within the recipient mycelium. This process is associated with growth retardation of the recipient and manifested by the formation of circular inhibition zones, named pocks. To characterize the unique Streptomyces DNA transfer machinery, we replaced each gene of the conjugative 12.1-kbp Streptomyces venezuelae plasmid pSVH1, with the exception of the rep gene required for plasmid replication, with a hexanucleotide sequence. Only deletion of traB , encoding the FtsK-like DNA translocase, affected efficiency of the transfer dramatically and abolished pock formation. Deletion of spdB3 , spd79 , or spdB2 had a minor effect on transfer but prevented pock formation and intramycelial plasmid spreading. Biochemical characterization of the encoded proteins revealed that the GntR-type regulator TraR recognizes a specific sequence upstream of spdB3 , while Orf108, SpdB2, and TraR bind to peptidoglycan. SpdB2 promoted spheroplast formation by T7 lysozyme and formed pores in artificial membranes. Bacterial two-hybrid analyses and chemical cross-linking revealed that most of the pSVH1-encoded proteins interacted with each other, suggesting a multiprotein DNA translocation complex of TraB and Spd proteins which directs intramycelial plasmid spreading. IMPORTANCE Mycelial soil bacteria of the genus Streptomyces evolved specific resistance genes as part of the biosynthetic gene clusters to protect themselves from their own antibiotic, making streptomycetes a huge natural reservoir of antibiotic resistance genes for dissemination by horizontal gene transfer. Streptomyces conjugation is a unique process, visible on agar plates with the mere eye by the formation of circular inhibition zones, called pocks. To understand the Streptomyces conjugative DNA transfer machinery, which does not involve a type IV secretion system (T4SS), we made a thorough investigation of almost all genes/proteins of the model plasmid pSVH1. We identified all genes involved in transfer and intramycelial plasmid spreading and showed that the FtsK-like DNA translocase TraB interacts with multiple plasmid-encoded proteins. Our results suggest the existence of a macromolecular DNA translocation complex that directs intramycelial plasmid spreading.
The Flatter, the Better
2015-05-27

We demonstrate the insides and outs of a query compiler based on the flattening transformation, a translation technique designed by the programming language community to derive efficient data-parallel implementations from iterative programs. Flattening admits the straightforward formulation of intricate query logic including deeply nested loops over (possibly ordered) data or the construction of rich data structures. To demonstrate the level of expressiveness that can be achieved, we will bring a compiler frontend that accepts queries embedded into the Haskell programming language. Compilation via flattening takes places in a series of simple steps all of which will be made tangible by the demonstration. The final output is a program of lifted primitive operations which existing query engines can efficiently implement. We provide backends based on PostgreSQL and VectorWise to make this point however, most set-oriented or data-parallel engines could benefit from a flattening-based query compiler.
A SQL Debugger Built from Spare Parts
2015-05-27

We demonstrate a new incarnation of Habitat, an observational debugger for SQL. In observational debugging, users highlight parts of a presumably faulty query to observe the evaluation of SQL subexpressions and learn about the query's actual runtime behavior. The present version of Habitat has been redesigned from scratch and employs a query instrumentation technique that exclusively relies on the SQL facilities of the underlying RDBMS. We particularly shed light on new features like (1) the debugging of recursive SQL queries and (2) the observation of row groups (before and after aggregation). Habitat can turn any reasonably modern SQL:1999 RDBMS into its own language-level SQL debugger.
ChemInform Abstract: Luminescence Matching with the Sensitivity Curve of the Human Eye: Optical Ceramics Mg8‐xMx(BN2)2N4 with M:Al (x:2) and M:Si (x:1).
2015-05-27

Abstract Mg 6 Al 2 (BN 2 ) 2 N 4 (I) and Mg 7 Si(BN 2 ) 2 N 4 (II) are prepared by solid state metathesis reaction (1100 °C) of MgCl 2 , Li 3 (BN 2 ), and AlN for (I) and of Mg 3 N 2 , BN, and Si 3 N 4 for (II).
Diminished levels of the soluble form of RAGE are related to poor survival in malignant melanoma
2015-05-28

RAGE is a central driver of tumorigenesis by sustaining an inflammatory tumor microenvironment. This study links the soluble forms of RAGE (sRAGE and esRAGE) with clinical outcome of melanoma patients. Moreover, tissue expression of RAGE was analyzed using immunohistochemistry on two independent tissue microarrays (TMA) containing 35 or 257 primary melanomas, and 41 or 22 benign nevi, respectively. Serum concentrations of sRAGE and esRAGE were measured in 229 Stage III–IV patients using ELISA and plasma concentrations of sRAGE were analyzed in an independent second cohort with 173 samples of Stage I–IV patients. In this cohort, three well‐described SNPs in the RAGE gene were analyzed. RAGE protein expression was highly upregulated in primary melanomas compared to benign nevi in the two TMA ( p &lt; 0.001 and p = 0.005) as well as in sun‐exposed melanomas ( p = 0.046). sRAGE and esRAGE were identified as prognostic markers for survival as diminished sRAGE ( p = 0.034) and esRAGE ( p = 0.012) serum levels correlated with poor overall survival (OS). Multivariate Cox regression analysis showed that diminished serum sRAGE was independently associated with poor survival ( p = 0.009). Moreover, diminished sRAGE was strongly associated with impaired OS in the second cohort ( p &lt; 0.001). Multivariate Cox regression analysis including the investigated SNPs revealed an independent correlation of the two interacting promoter SNPs with impaired OS. In conclusion, the soluble forms of RAGE and variants in its genetic locus are prognostic markers for survival in melanoma patients with high risk for progression.
On the meson mass spectrum in the covariant confined quark model
2015-05-28

We provide a new insight into the problem of generating the hadron mass\\nspectrum in the framework of the covariant confined quark model. One of the\\nunderlying principles of this model is the compositeness condition which means\\nthat the wave function renormalization constant of the elementary hadron is\\nequal to zero. In particular, this equation allows to express the Yukawa\\ncoupling of the meson fields to the constituent quarks as a function of other\\nmodel parameters. In addition to the compositeness condition we also employ a\\nfurther equation which relates the meson mass function to the Fermi coupling.\\nBoth equations guarantee that the Yukawa-type theory is equivalent to the\\nFermi-type theory thereby providing an interpretation of the meson field as the\\nbound state of its constituent fermions (quarks). We evaluate the\\nFermi-coupling as a function of meson (pseudoscalar and vector) masses and vary\\nthe values of the masses in such a way to obtain a smooth behavior for the\\nresulting curve. The mass spectrum obtained in this manner is found to be in\\ngood agreement with the experimental data. We also compare the behavior of our\\nFermi-coupling with the strong QCD coupling alpha_s calculated in an\\nQCD-inspired approach.\\n
Inhibition of hepatitis B virus replication in vivo by nucleoside analogues and siRNA
2015-05-28

Background / Aim: Hepatitis B Virus (HBV) causes acute and chronic infections which may result in severe liver diseases. Animal models to study new treatment options in vivo have several drawbacks. Therefore we were interested to establish a new small animal model where HBV replication and especially new treatment options can be studied easily.
The Arabidopsis GAGA-Binding Factor BASIC PENTACYSTEINE6 Recruits the POLYCOMB-REPRESSIVE COMPLEX1 Component LIKE HETEROCHROMATIN PROTEIN1 to GAGA DNA Motifs
2015-05-29

Polycomb-repressive complexes (PRCs) play key roles in development by repressing a large number of genes involved in various functions. Much, however, remains to be discovered about PRC-silencing mechanisms as well as their targeting to specific genomic regions. Besides other mechanisms, GAGA-binding factors in animals can guide PRC members in a sequence-specific manner to Polycomb-responsive DNA elements. Here, we show that the Arabidopsis (Arabidopsis thaliana) GAGA-motif binding factor protein basic pentacysteine6 (BPC6) interacts with like heterochromatin protein1 (LHP1), a PRC1 component, and associates with vernalization2 (VRN2), a PRC2 component, in vivo. By using a modified DNA-protein interaction enzyme-linked immunosorbant assay, we could show that BPC6 was required and sufficient to recruit LHP1 to GAGA motif-containing DNA probes in vitro. We also found that LHP1 interacts with VRN2 and, therefore, can function as a possible scaffold between BPC6 and VRN2. The lhp1-4 bpc4 bpc6 triple mutant displayed a pleiotropic phenotype, extreme dwarfism and early flowering, which disclosed synergistic functions of LHP1 and group II plant BPC members. Transcriptome analyses supported this synergy and suggested a possible function in the concerted repression of homeotic genes, probably through histone H3 lysine-27 trimethylation. Hence, our findings suggest striking similarities between animal and plant GAGA-binding factors in the recruitment of PRC1 and PRC2 components to Polycomb-responsive DNA element-like GAGA motifs, which must have evolved through convergent evolution.
Empagliflozin as add‐on to metformin in people with Type 2 diabetes
2015-05-29

Abstract Aims To investigate the long‐term efficacy and safety of empagliflozin as add‐on to metformin in people with Type 2 diabetes. Methods Of 637 participants treated with empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily for 24 weeks, 463 (72.7%) were treated in a double‐blind extension trial for ≥ 52 weeks. Prespecified exploratory endpoints included changes from baseline in HbA 1c , weight and blood pressure at week 76. Results Compared with placebo, adjusted mean changes from baseline in HbA 1c (overall baseline mean ± sd 63 ± 9 mmol/mol [7.9 ± 0.9%]) were −7 mmol/mol [(−0.6%) 95% CI −8, −5 mmol/mol (−0.8, −0.5%); P &lt; 0.001] and −8 mmol/mol [(−0.7%) 95% CI −10, −6 mmol/mol (−0.9, −0.6%); P &lt; 0.001], for empagliflozin 10 mg and 25 mg, respectively. Compared with placebo, adjusted mean changes from baseline in weight were −1.9 kg (95% CI −2.5, −1.3; P &lt; 0.001) and −2.2 kg (95% CI −2.8, −1.6; P &lt; 0.001) for empagliflozin 10 mg and 25 mg, respectively. Empagliflozin led to sustained reductions in systolic blood pressure vs. placebo. Adverse events were reported in 77.7, 80.2 and 72.0% of participants on placebo, empagliflozin 10 mg and empagliflozin 25 mg, respectively. Confirmed hypoglycaemic adverse events (glucose ≤ 3.9 mmol/l and/or event requiring assistance) were reported in 3.4, 4.1 and 4.2% of participants in these groups, respectively. Conclusions In people with Type 2 diabetes, empagliflozin 10 mg and 25 mg given as add‐on to metformin for 76 weeks were well tolerated and led to sustained reductions in HbA 1c , weight and systolic blood pressure.
The fluorescent pentameric oligothiophene pFTAA identifies filamentous tau in live neurons cultured from adult P301S tau mice
2015-05-29

Identification of fluorescent dyes that label the filamentous protein aggregates characteristic of neurodegenerative disease, such as β-amyloid and tau in Alzheimer's disease, in a live cell culture system has previously been a major hurdle. Here we show that pentameric formyl thiophene acetic acid (pFTAA) fulfills this function in living neurons cultured from adult P301S tau transgenic mice. Injection of pFTAA into 5-month-old P301S tau mice detected cortical and DRG neurons immunoreactive for AT100, an antibody that identifies solely filamentous tau, or MC1, an antibody that identifies a conformational change in tau that is commensurate with neurofibrillary tangle formation in Alzheimer's disease brains. In fixed cultures of dorsal root ganglion (DRG) neurons, pFTAA binding, which also identified AT100 or MC1+ve neurons, followed a single, saturable binding curve with a half saturation constant of 0.14 μM, the first reported measurement of a binding affinity of a beta-sheet reactive dye to primary neurons harboring filamentous tau. Treatment with formic acid, which solubilizes filamentous tau, extracted pFTAA, and prevented the re-binding of pFTAA and MC1 without perturbing expression of soluble tau, detected using an anti-human tau (HT7) antibody. In live cultures, pFTAA only identified DRG neurons that, after fixation, were AT100/MC1+ve, confirming that these forms of tau pre-exist in live neurons. The utility of pFTAA to discriminate between living neurons containing filamentous tau from other neurons is demonstrated by showing that more pFTAA+ve neurons die than pFTAA-ve neurons over 25 days. Since pFTAA identifies fibrillar tau and other misfolded proteins in living neurons in culture and in animal models of several neurodegenerative diseases, as well as in human brains, it will have considerable application in sorting out disease mechanisms and in identifying disease-modifying drugs that will ultimately help establish the mechanisms of neurodegeneration in human neurodegenerative diseases.
High-density preculture of PBMCs restores defective sensitivity of circulating CD8 T cells to virus- and tumor-derived antigens
2015-05-29

Key Points CD8 memory T cells in PBMCs are antigen-hyporesponsive due to loss of priming by tissue-dependent interactions. Preculture at high cell density allows the detection of antiviral and antitumor responses that may be overlooked without this step.
Fine control of drug delivery for cochlear implant applications
2015-05-29

Cochlear implants are neuroprostheses that are inserted into the inner ear to directly electrically stimulate the auditory nerve, thus replacing lost cochlear receptors, the hair cells. The reduction of the gap between electrodes and nerve cells will contribute to technological solutions simultaneously increasing the frequency resolution, the sound quality and the amplification of the signal. Recent findings indicate that neurotrophins (NTs) such as brain derived neurotrophic factor (BDNF) stimulate the neurite outgrowth of auditory nerve cells by activating Trk receptors on the cellular surface (1–3). Furthermore, small-size TrkB receptor agonists such as di-hydroxyflavone (DHF) are now available, which activate the TrkB receptor with similar efficiency as BDNF, but are much more stable (4). Experimentally, such molecules are currently used to attract nerve cells towards, for example, the electrodes of cochlear implants. This paper analyses the scenarios of low dose aspects of controlled release of small-size Trk receptor agonists from the coated CI electrode array into the inner ear. The control must first ensure a sufficient dose for the onset of neurite growth. Secondly, a gradient in concentration needs to be maintained to allow directive growth of neurites through the perilymph-filled gap towards the electrodes of the implant. We used fluorescein as a test molecule for its molecular size similarity to DHF and investigated two different transport mechanisms of drug dispensing, which both have the potential to fulfil controlled low-throughput drug-deliverable requirements. The first is based on the release of aqueous fluorescein into water through well-defined 60-μm size holes arrays in a membrane by pure osmosis. The release was both simulated using the software COMSOL and observed experimentally. In the second approach, solid fluorescein crystals were encapsulated in a thin layer of parylene (PPX), hence creating random nanometer-sized pinholes. In this approach, the release occurred due to subsequent water diffusion through the pinholes, dissolution of the fluorescein and then release by out-diffusion. Surprisingly, the release rate of solid fluorescein through the nanoscopic scale holes was found to be in the same order of magnitude as for liquid fluorescein release through microscopic holes.
Single-spin asymmetries inWboson production at next-to-leading order
2015-05-29

We present an analytic next-to-leading order QCD calculation of the partonic cross sections for single-inclusive lepton production in hadronic collisions, when the lepton originates from the decay of an intermediate electroweak boson and is produced at high transverse momentum. In particular, we consider the case of incoming longitudinally polarized protons for which parity-violating single-spin asymmetries arise that are exploited in the boson program at RHIC to constrain the proton's helicity parton distributions. Our calculation enables a very fast and efficient numerical computation of the relevant spin asymmetries at RHIC, which is an important ingredient for the inclusion of RHIC data in a global analysis of nucleon helicity structure. We confirm the validity of our calculation by comparing with an existing code that treats the next-to-leading order cross sections entirely numerically by Monte-Carlo integration techniques. We also provide new comparisons of the present RHIC data with results for some of the sets of polarized parton distributions available in the literature.
XMM-Newtonobservation of SNR J0533–7202 in the Large Magellanic Cloud
2015-05-29

Aims. We present an X-ray study of the supernova remnant SNR J0533-7202 in the Large Magellanic Cloud (LMC) and determine its physical characteristics based on its X-ray emission. Methods. We observed SNR J0533-7202 with XMM-Newton (flare-filtered exposure times of 18 ks EPIC-pn and 31 ks EPIC-MOS1/MOS2). We produced X-ray images of the SNR, performed an X-ray spectral analysis, and compared the results to multi-wavelength studies. Results. The distribution of X-ray emission is highly non-uniform, with the south-west region brighter than the north-east. The X-ray emission is correlated with the radio emission from the remnant. We determine that this morphology is likely due to the SNR expanding into a non-uniform ambient medium and not an absorption effect. We estimate the size to be 53.9 (\\pm 3.4) x 43.6 (\\pm 3.4) pc, with the major axis rotated ~64 degrees east of north. We find no spectral signatures of ejecta and infer that the X-ray plasma is dominated by swept-up interstellar medium. Using the spectral fit results and the Sedov self-similar solution, we estimate an age of ~17-27 kyr, with an initial explosion energy of (0.09-0.83) x 10^51 erg. We detected an X-ray source located near the centre of the remnant, namely XMMU J053348.2-720233. The source type could not be conclusively determined due to the lack of a multi-wavelength counterpart and low X-ray counts. We find that it is likely either a background active galactic nucleus or a low-mass X-ray binary in the LMC. Conclusions. We detected bright thermal X-ray emission from SNR J0533-7202 and determined that the remnant is in the Sedov phase of its evolution. The lack of ejecta emission prohibits us from typing the remnant with the X-ray data. Therefore, the likely Type Ia classification based on the local stellar population and star formation history reported in the literature cannot be improved upon.
Imaging of Apoptosis: The Need to Distinguish Tracer Uptake Rate from Regional Contribution of Blood Flow
2015-05-29

In oncology, PET is known to contribute substantially to localization of tumors and metastases and to control of therapy. One particularly attractive application is the assay of apoptosis induced by chemotherapy or radiation. Various tracers, such as 99mTc-annexin-V and 18F-ML-10, are under