bluuebunny/crossref_metadata_2025_split huggingface dataset:
FDG and FLT-PET for Early measurement of response to 37.5 mg daily sunitinib therapy in metastatic renal cell carcinoma
Authors: Horn Kevin P. , Yap Jeffrey T. , Agarwal Neeraj , Morton Kathryn A. , Kadrmas Dan J. , Beardmore Britney , Butterfield Regan I. , Boucher Kenneth , Hoffman John M. 
Published: September 2015

Abstract

Background
Metastatic renal cell carcinoma has a poor prognosis and an intrinsic resistance to standard treatment. Sunitinib is an oral receptor tyrosine kinase inhibitor that has been used as a first-line targeted therapy in metastatic renal cell carcinoma. While computed tomography (CT) is currently the gold standard for response assessment in oncological trials, numerous studies have shown that positron emission tomography (PET) imaging can provide information predictive of tumor response to treatment earlier than the typical interval for standard of care follow-up CT imaging. In this exploratory study we sought to characterize early tumor response in patients with metastatic renal cell carcinoma treated with continuous daily 37.5 mg sunitinib therapy.

Methods
Twenty patients underwent dynamic acquisition positron emission tomography (PET) imaging using 18 F-fluorodeoxyglucose (FDG) and 18 F-fluorothymidine (FLT) at baseline and early in treatment (after 1, 2, 3 or 4 weeks) with 37.5 mg continuous daily dosing of sunitinib. Semi-quantitative analyses were performed to characterize the tumor metabolic (FDG) and proliferative (FLT) responses to treatment.

Results
Proliferative responses were observed in 9/19 patients and occurred in 2 patients at one week (the earliest interval evaluated) after the initiation of therapy. A metabolic response was observed in 5/19 patients, however this was not observed until after two weeks of therapy were completed. Metabolic progression was observed in 2/19 patients and proliferative progression was observed in 1/19 patients. Baseline FDG-PET tumor maximum standardized uptake values correlated inversely with overall survival (p = 0.0036). Conversely, baseline 18 F-fluorothymidine PET imaging did not have prognostic value (p = 0.56) but showed a greater early response rate at 1–2 weeks after initiating therapy.

Conclusions
While preliminary in nature, these results show an immediate and sustained proliferative response followed by a delayed metabolic response beginning after two weeks in metastatic renal cell carcinoma treated with a continuous daily dose of 37.5 mg sunitinib. The results provide evidence of tumor response to lower-dose sunitinib while also supporting the inclusion of PET imaging as a tool for early assessment in oncological clinical trials.

Trial registration
ID: NCT00694096
Potential of the bioflavonoids in the prevention/treatment of ocular disorders
Authors: Majumdar Soumyajit , Srirangam Ramesh 
Published: September 2015

Abstract

Objectives
Flavonoids are a common group of plant polyphenols that give colour and flavour to fruits and vegetables. In recent years, flavonoids have gained importance in the pharmaceutical field through their beneficial effects on human health and are widely available as nutritional supplements. Several pharmacological actions of the bioflavonoids may be useful in the prevention or treatment of ocular diseases responsible for vision loss such as diabetic retinopathy, macular degeneration and cataract. This review aims to summarize the potential therapeutic applications of various bioflavonoids in different ocular diseases and also discusses delivery of these agents to the ocular tissues.

Key findings
It is apparent that the flavonoids are capable of acting on various mechanisms or aetiological factors responsible for the development of different sight threatening ocular diseases. From a drug delivery perspective, ocular bioavailability depends on the physicochemical and biopharmaceutical characteristics of the selected flavonoids and very importantly the route of administration.

Summary
The potential therapeutic applications of various bioflavonoids in ocular diseases is reviewed and the delivery of these agents to the ocular tissues is discussed. Whereas oral administration of bioflavonoids may demonstrate some pharmacological activity in the outer sections of the posterior ocular segment, protection of the retinal ganglionic cells in vivo may be limited by this delivery route. Systemic or local administration of these agents may yield much higher and effective concentrations of the parent bioflavonoids in the ocular tissues and at much lower doses.
Effects of sublethal doses of glyphosate on honeybee navigation
Authors: Balbuena María Sol , Tison Léa , Hahn Marie-Luise , Greggers Uwe , Menzel Randolf , Farina Walter M. 
Published: September 2015

ABSTRACTGlyphosate (GLY) is a herbicide that is widely used in agriculture for weed control. Although reports about the impact of GLY in snails, crustaceans and amphibians exist, few studies have investigated its sublethal effects in non-target organisms such as the honeybee Apis mellifera, the main pollen vector in commercial crops. Here, we tested whether exposure to three sublethal concentrations of GLY (2.5, 5 and 10 mg l−1: corresponding to 0.125, 0.250 and 0.500 μg per animal) affects the homeward flight path of honeybees in an open field. We performed an experiment in which forager honeybees were trained to an artificial feeder, and then captured, fed with sugar solution containing traces of GLY and released from a novel site either once or twice. Their homeward trajectories were tracked using harmonic radar technology. We found that honeybees that had been fed with solution containing 10 mg l−1 GLY spent more time performing homeward flights than control bees or bees treated with lower concentrations. They also performed more indirect homing flights. Moreover, the proportion of direct homeward flights performed after a second release from the same site increased in control bees but not in treated bees. These results suggest that, in honeybees, exposure to levels of GLY commonly found in agricultural settings impairs the cognitive capacities needed to retrieve and integrate spatial information for a successful return to the hive. Therefore, honeybee navigation is affected by ingesting traces of the most widely used herbicide worldwide, with potential long-term negative consequences for colony foraging success.
Directional flow sensing by passively stable larvae
Authors: Fuchs Heidi L. , Christman Adam J. , Gerbi Gregory P. , Hunter Elias J. , Diez F. Javier 
Published: September 2015

ABSTRACTMollusk larvae have a stable, velum-up orientation that may influence how they sense and react to hydrodynamic signals applied in different directions. Directional sensing abilities and responses could affect how a larva interacts with anisotropic fluid motions, including those in feeding currents and in boundary layers encountered during settlement. Oyster larvae (Crassostrea virginica) were exposed to simple shear in a Couette device and to solid-body rotation in a single rotating cylinder. Both devices were operated in two different orientations, one with the axis of rotation parallel to the gravity vector, and one with the axis perpendicular. Larvae and flow were observed simultaneously with near-infrared particle-image velocimetry, and behavior was quantified as a response to strain rate, vorticity and centripetal acceleration. Only flows rotating about a horizontal axis elicited the diving response observed previously for oyster larvae in turbulence. The results provide strong evidence that the turbulence-sensing mechanism relies on gravity-detecting organs (statocysts) rather than mechanosensors (cilia). Flow sensing with statocysts sets oyster larvae apart from zooplankters such as copepods and protists that use external mechanosensors in sensing spatial velocity gradients generated by prey or predators. Sensing flow-induced changes in orientation, rather than flow deformation, would enable more efficient control of vertical movements. Statocysts provide larvae with a mechanism of maintaining their upward swimming when rotated by vortices and initiating dives toward the seabed in response to the strong turbulence associated with adult habitats.
Should electoral management bodies encourage voting? The case for a civic education role
Authors: Lewis J. P. 
Published: September 2015

Abstract
In 2014, the Canadian Conservative government caused much concern and debate amongst academics, the media and public over proposed changes to the Elections Act, which would restrict communications from the Chief Electoral Officer. The debate over Bill C-23 provides the opportunity to explore the role of electoral management bodies in civic education. This article argues that based on policy precedent at the provincial level and general institutional support across Canada that there is a case to be made for a civic education role for EMBs, going beyond the responsibility of simply providing answers on ‘How to Vote’ but also suggesting answers to the question of ‘Why Vote’.
Ethylsulphate-Based Ionic Liquids in the Liquid–Liquid Extraction of Pyrrole and Pyridine from Isododecane at 298.15 K
Authors: Hazim Chan Nurshakirin , Farzana Hizaddin Hanee , Anantharaj Ramalingam , Banerjee Tamal 
Published: September 2015

Abstract
Ternary liquid-liquid equilibria for four systems containing ionic liquids {1-ethyl-3-methylimidazolium ethylsulphate ([EMIM][EtSO4]) and 1-ethyl-3-methylpyridinium ethylsulphate ([EMPY][EtSO4])}(1)+pyrrole/pyridine(2)+isododecane (3) have been determined at 298.15 K. The solute distribution coefficient and selectivity were calculated from experimental LLE data. All systems showed high distribution coefficient and selectivity values at the entire range of pyrrole or pyridine in feed. The consistency of experimental data was ascertained by applying the Othmer-Tobias and hand equations. Furthermore, the experimental LLE data have been compared and correlated using COSMO-RS, NRTL and UNIQUAC models. The influence of aromatic structure without inside ring of cation has a significant role on denitrification process at 298.15 K.
Mechanical and Electrochemical Characterization of Super-Solidus Sintered Austenitic Stainless Steel (316L)
Authors: Muthuchamy A. , Raja Annamalai A. , Ranka Rishabh 
Published: September 2015

Abstract
The present study compares the mechanical and electrochemical behaviour of austenitic (AISI 316L) stainless steel compacted at various pressures (200, 400 and 600 MPa) and conventionally sintered at super-solidus temperature of 1,400°C. The electrochemical behaviour was investigated in 0.1 N H2SO4 solution by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). The shrinkage decreased and densification has been increased with increasing pressure. The mechanical and electrochemical behaviour with pressure has been correlated with densification response and microstructure (pore type, volume and morphology). Highest densification (~92% theoretical) achieved at 600 MPa (compaction pressure) and 1,400°C (sintering temperature) resulted in excellent combination of tensile strength and ductility (456 ± 40 MPa, 25 ± 1.1%), while showing excellent corrosion resistance (0.1 mmpy or 4.7 mpy).
Temperature Analysis of the Water Supply System of a Dairy Company by Means of a Simulation Model
Authors: Marchini Davide , Rinaldi Marta , Montanari Roberto , Bottani Eleonora , Solari Federico 
Published: September 2015

Abstract
This paper builds upon the study by Marchini et al. (2014, International Journal of Food Engineering, pp. 557–571) and represents the second part of a research project whose general aim was to analyse and optimize, through simulation, the water distribution system of a dairy company. In the first paper, the authors focused on finding opportunities for recycling water in the distribution system of the targeted company, i.e. a dairy company located near Parma (Italy) and manufacturing Parmigiano Reggiano cheese and butter. In this work, we go ahead by analysing the thermal properties (such as, primarily, the temperature) of the water used inside the distribution system and of that discharged. To this purpose, we add the relevant thermal equations to the MS ExcelTM simulation model developed in the first study. The resulting model is able to derive the temperature trend of water inside all the tanks of the distribution system. Situations where the temperature of the water used for rinsing is higher than the maximum allowed value of approx. 25°C are also highlighted and suggestions for improvement are proposed.
Prosody, phonological domains and the structure of roots, stems and words in the Munda languages in a comparative/historical light
Authors: Anderson Gregory D. S. 
Published: September 2015

Abstract
Munda languages reveal competing word-level vs. phrase-level domains with respect to prosody, with weak-strong vs. strong-weak patterns, respectively. The prosodically strong syllable at the word-level is a root element that reflects cognacy across the family, while the word-frames they are embedded in frequently do not. Such a pattern of cognate roots and non-cognate word-frames is attested across the Austroasiatic phylum. The types of word-frames that such roots are embedded in reflect traces of a once-active system of semantically transparent prefixation or noun class marking, in addition to now mainly frozen systems of noun-verb stem compounding or noun incorporation. Word-level prosody in Munda is archaic, while phrase-level prosodic features are secondary and reflect local South Asian norms.
A new numerical scheme for the CIR process
Authors: Halidias Nikolaos 
Published: September 2015

Abstract
In this paper we generalize an explicit numerical scheme for the CIR process that we have proposed before.
The advantage of the new proposed scheme is that preserves positivity and is well posed for a (little bit) broader set of parameters among the positivity preserving schemes. The order of convergence is at least logarithmic in general and for a smaller set of parameters is at least 1/4.
“Life is Short, the Art is Long”: An Interpretation of the First Hippocratic Aphorism by an East Syriac Monk in the 7th Century Iraq (Isaac of Nineveh, Kephalaia gnostica 3,62)
Authors: Kessel Grigory 
Published: September 2015

AbstractThe so-called Second Part of monastic writings composed by the 7th century East Syriac author Isaac of Nineveh contains a paraphrased citation from the famous beginning of Hippocrates’ Aphorismoi. The article tackles the issue of Isaac’s awareness of the aphorism and tries to reconstruct its interpretation by the author. Though medical texts were available in the East Syriac monastic milieu of that time, it is not likely that Isaac had at his disposal a complete Syriac translation of the Aphorismoi, but rather his acquaintance with the aphorism was mediated by a source that would more likely have been read in monastic context. A good example offers the treatise De anima by the early 5th century monastic author John the Solitary, whose works exercised profound influence upon the entire East Syriac monastic tradition, including Isaac of Nineveh. The given case of a monastic interpretation of a piece of secular wisdom is an illustrative showcase that provides an opportunity to observe a particular sensitivity of the Syriac tradition to medicine and its power to embed it within an appropriate context.
„Wahrheit ist Gott“: Hl. Isaak von Ninive über die Lektüre der Eremiten
Authors: Bumazhnov Dmitrij F. 
Published: September 2015

AbstractThe article analyses two texts by Isaac of Nineveh (7th century) where he speaks explicitly about various kinds of literature apt or unapt for reading by hermits. Focusing on the general context of these statements in the Eastern Syriac monasticism of the time in question and especially on their significance in the works of Isaac the article explores Isaac of Nineveh’s attitude towards reading and education of hermits. Special attention is paid to the problem of monastic controversies concerning religious matters and to Isaac’s attempts of settling them
Comparison of Object Recognition Behavior in Human and Monkey
Authors: Rajalingham Rishi , Schmidt Kailyn , DiCarlo James J. 
Published: September 2015

Although the rhesus monkey is used widely as an animal model of human visual processing, it is not known whether invariant visual object recognition behavior is quantitatively comparable across monkeys and humans. To address this question, we systematically compared the core object recognition behavior of two monkeys with that of human subjects. To test true object recognition behavior (rather than image matching), we generated several thousand naturalistic synthetic images of 24 basic-level objects with high variation in viewing parameters and image background. Monkeys were trained to perform binary object recognition tasks on a match-to-sample paradigm. Data from 605 human subjects performing the same tasks on Mechanical Turk were aggregated to characterize “pooled human” object recognition behavior, as well as 33 separate Mechanical Turk subjects to characterize individual human subject behavior. Our results show that monkeys learn each new object in a few days, after which they not only match mean human performance but show a pattern of object confusion that is highly correlated with pooled human confusion patterns and is statistically indistinguishable from individual human subjects. Importantly, this shared human and monkey pattern of 3D object confusion is not shared with low-level visual representations (pixels, V1+; models of the retina and primary visual cortex) but is shared with a state-of-the-art computer vision feature representation. Together, these results are consistent with the hypothesis that rhesus monkeys and humans share a common neural shape representation that directly supports object perception.SIGNIFICANCE STATEMENTTo date, several mammalian species have shown promise as animal models for studying the neural mechanisms underlying high-level visual processing in humans. In light of this diversity, making tight comparisons between nonhuman and human primates is particularly critical in determining the best use of nonhuman primates to further the goal of the field of translating knowledge gained from animal models to humans. To the best of our knowledge, this study is the first systematic attempt at comparing a high-level visual behavior of humans and macaque monkeys.
Soluble Tumor Necrosis Factor Alpha Promotes Retinal Ganglion Cell Death in Glaucoma via Calcium-Permeable AMPA Receptor Activation
Authors: Cueva Vargas Jorge L. , Osswald Ingrid K. , Unsain Nicolas , Aurousseau Mark R. , Barker Philip A. , Bowie Derek , Di Polo Adriana 
Published: September 2015

Loss of vision in glaucoma results from the selective death of retinal ganglion cells (RGCs). Tumor necrosis factor α (TNFα) signaling has been linked to RGC damage, however, the mechanism by which TNFα promotes neuronal death remains poorly defined. Using anin vivorat glaucoma model, we show that TNFα is upregulated by Müller cells and microglia/macrophages soon after induction of ocular hypertension. Administration of XPro1595, a selective inhibitor of soluble TNFα, effectively protects RGC soma and axons. Using cobalt permeability assays, we further demonstrate that endogenous soluble TNFα triggers the upregulation of Ca2+-permeable AMPA receptor (CP-AMPAR) expression in RGCs of glaucomatous eyes. CP-AMPAR activation is not caused by defects in GluA2 subunit mRNA editing, but rather reflects selective downregulation of GluA2 in neurons exposed to elevated eye pressure. Intraocular administration of selective CP-AMPAR blockers promotes robust RGC survival supporting a critical role for non-NMDA glutamate receptors in neuronal death. Our study identifies glia-derived soluble TNFα as a major inducer of RGC death through activation of CP-AMPARs, thereby establishing a novel link between neuroinflammation and cell loss in glaucoma.SIGNIFICANCE STATEMENTTumor necrosis factor α (TNFα) has been implicated in retinal ganglion cell (RGC) death, but how TNFα exerts this effect is poorly understood. We report that ocular hypertension, a major risk factor in glaucoma, upregulates TNFα production by Müller cells and microglia. Inhibition of soluble TNFα using a dominant-negative strategy effectively promotes RGC survival. We find that TNFα stimulates the expression of calcium-permeable AMPA receptors (CP-AMPAR) in RGCs, a response that does not depend on abnormal GluA2 mRNA editing but on selective downregulation of the GluA2 subunit by these neurons. Consistent with this, CP-AMPAR blockers promote robust RGC survival supporting a critical role for non-NMDA glutamate receptors in glaucomatous damage. This study identifies a novel mechanism by which glia-derived soluble TNFα modulates neuronal death in glaucoma.
Oligodendrocyte Regeneration and CNS Remyelination Require TACE/ADAM17
Authors: Palazuelos Javier , Klingener Michael , Raines Elaine W. , Crawford Howard C. , Aguirre Adan 
Published: September 2015

The identification of the molecular network that supports oligodendrocyte (OL) regeneration under demyelinating conditions has been a primary goal for regenerative medicine in demyelinating disorders. We recently described an essential function for TACE/ADAM17 in regulating oligodendrogenesis during postnatal myelination, but it is unknown whether this protein also plays a role in OL regeneration and remyelination under demyelinating conditions. By using genetic mouse models to achieve selective gain- or loss-of-function of TACE or EGFR in OL lineage cellsin vivo, we found that TACE is critical for EGFR activation in OLs following demyelination, and therefore, for sustaining OL regeneration and CNS remyelination. TACE deficiency in oligodendrocyte progenitor cells following demyelination disturbs OL lineage cell expansion and survival, leading to a delay in the remyelination process. EGFR overexpression in TACE deficient OLsin vivorestores OL development and postnatal CNS myelination, but also OL regeneration and CNS remyelination following demyelination. Our study reveals an essential function of TACE in supporting OL regeneration and CNS remyelination that may contribute to the design of new strategies for therapeutic intervention in demyelinating disorders by promoting oligodendrocyte regeneration and myelin repair.SIGNIFICANCE STATEMENTOligodendrocyte (OL) regeneration has emerged as a promising new approach for the treatment of demyelinating disorders. By using genetic mouse models to selectively delete TACE expression in oligodendrocyte progenitors cells (OPs), we found that TACE/ADAM17 is required for supporting OL regeneration following demyelination. TACE genetic depletion in OPs abrogates EGFR activation in OL lineage cells, and perturbs cell expansion and survival, blunting the process of CNS remyelination. Moreover, EGFR overexpression in TACE-deficient OPsin vivoovercomes the defects in OL development during postnatal development but also OL regeneration during CNS remyelination. Our study identifies TACE as an essential player in OL regeneration that may provide new insights in the development of new strategies for promoting myelin repair in demyelinating disorders.