bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amphiphilic Copolymers Shuttle Drugs Across the Blood–Brain Barrier
Authors: Clemens‐Hemmelmann Mirjam , Kuffner Christiane , Metz Verena , Kircher Linda , Schmitt Ulrich , Hiemke Christoph , Postina Rolf , Zentel Rudolf 
Published: January 2016

Medical treatment of diseases of the central nervous system requires transport of drugs across the blood–brain barrier (BBB). Here, it is extended previously in vitro experiments with a model compound to show that the non‐water‐soluble and brain‐impermeable drug domperidone (DOM) itself can be enriched in the brain by use of an amphiphilic copolymer as a carrier. This carrier consists of poly(N‐(2‐hydroxypropyl)‐methacrylamide), statistically copolymerized with 10 mol% hydrophobic lauryl methacrylate, into whose micellar aggregates DOM is noncovalently absorbed. As tested in a BBB model efficient transport of DOM across, the BBB is achievable over a wide range of formulations, containing 0.8 to 35.5 wt% domperidone per copolymer. In neither case, the polymer itself is translocated across the BBB model. In vivo experiments in mice show that already 10 min after intraperitoneal injection of the polymer/domperidone (PolyDOM) formulation, domperidone can be detected in blood and in the brain. Highest serum and brain levels of domperidone are detected 40 min after injection. At that time point serum domperidone is increased 48‐fold. Most importantly, domperidone is exclusively detectable in high amounts in the brain of PolyDOM injected mice and not in mice injected with bare domperidone.
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Effect of PCL/PEG‐Based Membranes on Actinorhodin Production in Streptomyces coelicolor Cultivations
Authors: Scaffaro Roberto , Lopresti Francesco , Sutera Alberto , Botta Luigi , Fontana Rosa Maria , Puglia Anna Maria , Gallo Giuseppe 
Published: January 2016

The actinomycetes, Gram‐positive filamentous bacteria, are the most prolific source of natural occurring antibiotics. At an industrial level, antibiotics from actinomycete strains are produced by means of submerged fermentations, where one of the major factors negatively affecting bioproductivity is the pellet‐shaped biomass growth. The immobilization of microorganisms on properly chosen supports prevents cell–cell aggregation resulting in improving the biosynthetic capability. Thus, novel porous biopolymer‐based devices are developed by combining melt mixing and particulate leaching. In particular, polycaprolactone (PCL), polyethylene glycol (PEG), and sodium chloride (NaCl) with different grain sizes are used to prepare PCL/PEG/NaCl blends in the melt. These blends are then leached to obtain PCL‐based porous membranes that are used as solid support for the growth of Streptomyces coelicolor, a model streptomycete used to produce various antibiotics including the blue colored actinorhodin (ACT). Thereafter, the effect of the devices' characteristics on the bacterial growth and on the production ACT is evaluated. The results showed that ACT production is strongly dependent on the pore size distribution of the device. Moreover, membranes with pores ranging from 90 to 110 μm are able to offer a potential improvement in volumetric productivity of ACT if compared to conventional submerged liquid culture.
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Effect of Dissolved Polymer on the Elasticity and Plasticity of a Lyotropic Lamellar Mesophase
Authors: Herrmann Laure , Kékicheff Patrick 
Published: January 2016

SummaryUsing the Surface Force Apparatus (SFA) technique, direct force–distance measurements between mica surfaces immersed in a polymer‐doped lamellar phase are presented. In the aqueous layers separating the charged and undulating bilayers of sodium dodecyl sulfate (SDS)/octanol, water is replaced by a polyethylene glycol aqueous solution (PEG,Mw20000 g/mol). As the mesophases align with the layers parallel to the solid mica surfaces the measurements yield structural information on the confined mesophases as well as bulk elastic properties. Keeping the membrane volume fraction constant the PEG dissolution results in a marked decrease in the elastic compressibility modulus,. This indicates a softening of the repulsive interactions between the lamellae mediated by polymer adsorption on the bilayers/aqueous solution interface. Insights into the behavior of the mesophases in confined geometries and thereby their stabilization mechanism are gained by noting a plastic contribution due to the presence of edge dislocations in the wedge‐like confinement geometry.
SVD analysis of Array transmission and reception and its use for bootstrapping calibration
Authors: Brunner David O. , Pruessmann Klaas P. 
Published: January 2016

PurposeNoise‐optimal reconstruction of array transmitter calibrations would ideally require knowledge of the receive array sensitivities which can often only be measured once the transmitter is calibrated to provide sufficient coverage. This poses often a problem in bootstrapping transmit‐receive arrays particularly at ultrahigh fields.MethodsSaid problem is resolved by formulating the local transmit‐receive efficiency of the array setup as a bilinear form and deriving therefrom a noise‐optimal, joint reconstruction of the calibration data resulting in the relative sensitivities of the used transmitters and receivers.ResultsRetrieval and reconstruction of parallel transmission calibration data in phantoms and in vivo are presented using an eight‐channel parallel transmit setup with up to 16 receivers using strip‐line TR arrays and parallel transmission by traveling waves.ConclusionData sets from calibration scans are reconstructed robustly and with optimal signal‐to‐noise ratio. The found array signal gain is furthermore a direct performance measure for array transmitter and receiver combinations. The concomitantly obtained image was shown to have maximum coverage of the subject. Magn Reson Med 76:1730–1740, 2016. © 2016 International Society for Magnetic Resonance in Medicine
Preclinical pharmacology and pharmacokinetics of CERC‐301, a GluN2B‐selective N‐methyl‐D‐aspartate receptor antagonist
Authors: Garner Rachel , Gopalakrishnan Shobha , McCauley John A. , Bednar Rodney A. , Gaul Stanley L. , Mosser Scott D. , Kiss Laszlo , Lynch Joseph J. , Patel Shil , Fandozzi Christine , Lagrutta Armando , Briscoe Richard , Liverton Nigel J. , Paterson Blake M. , Vornov James J. , Mazhari Reza 
Published: January 2016

AbstractThe preclinical pharmacodynamic and pharmacokinetic properties of 4‐methylbenzyl (3S, 4R)‐3‐fluoro‐4‐[(Pyrimidin‐2‐ylamino) methyl] piperidine‐1‐carboxylate (CERC‐301), an orally bioavailable selective N‐methyl‐D‐aspartate (NMDA) receptor subunit 2B (GluN2B) antagonist, were characterized to develop a translational approach based on receptor occupancy (RO) to guide CERC‐301 dose selection in clinical trials of major depressive disorder. CERC‐301 demonstrated high‐binding affinity (Ki, 8.1 nmol L−1) specific to GluN2B with an IC50 of 3.6 nmol L−1 and no off‐target activity. CERC‐301 efficacy was demonstrated in the forced swim test with an efficacy dose (ED50) of 0.3–0.7 mg kg−1 (RO, 30–50%); increase in locomotor activity was observed at ED50 of 2 mg kg−1, corresponding to an RO of 75%. The predicted 50% RO concentration (Occ50) in humans was 400 nmol L−1, similar to that predicted for rat, dog, and monkey (300, 200, and 400 nmol L−1, respectively). Safety pharmacology and neurotoxicity studies raised no specific safety concerns. A first‐in‐human study in healthy males demonstrated a dose‐proportional pharmacokinetic profile, with Tmax of ~1 h and t1/2 of 12–17 h. Based on the preclinical and pharmacodynamic data, doses of ≥8 mg in humans are hypothesized to have an acceptable safety profile and result in clinically relevant peak plasma exposure.
Bioequivalence of saxagliptin/dapagliflozin fixed‐dose combination tablets compared with coadministration of the individual tablets to healthy subjects
Authors: Vakkalagadda Blisse , Vetter Marion L. , Rana Jignasa , Smith Charles H. , Huang Jian , Karkas Jennifer , Boulton David W. , LaCreta Frank 
Published: January 2016

AbstractSaxagliptin and dapagliflozin are individually indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The bioequivalence of saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg fixed‐dose combination (FDC) tablets compared with coadministration of the individual tablets and the food effect on both strengths of saxagliptin/dapagliflozin FDCs were evaluated in this open‐label, randomized, single‐dose crossover study. Healthy subjects were randomized to saxagliptin 2.5 mg + dapagliflozin 5 mg fasted, 2.5/5 mg FDC fasted, 2.5/5 mg FDC fed (Cohort 1) or saxagliptin 5 mg + dapagliflozin 10 mg fasted, 5/10 mg FDC fasted, 5/10 mg FDC fed (Cohort 2). Serial blood samples for pharmacokinetics of saxagliptin and dapagliflozin were obtained predose and up to 60 h postdose. Bioequivalence of FDC tablets versus individual components was concluded if the 90% CIs for FDC to individual component geometric mean ratios of Cmax, AUC0‐T, and AUCinf of both analytes were between 0.80 and 1.25. Seventy‐two subjects were randomized; 71 (98.6%) completed the study. Saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg FDC tablets were bioequivalent to the individual tablets administered concomitantly. Food had no clinically meaningful effect on saxagliptin or dapagliflozin overall systemic exposure. Saxagliptin/dapagliflozin FDC tablets were bioequivalent to coadministration of the individual components in healthy subjects under fasted conditions and food had no clinically meaningful effect on bioavailability.
Determination of bisphenol A‐glucuronide in human urine using ultrahigh‐pressure liquid chromatography/tandem mass spectrometry
Authors: Hauck Zane Z. , Huang Ke , Li Guannan , van Breemen Richard B. 
Published: January 2016

RationaleUsed widely as a plasticizer and as a monomer for plastics, bisphenol A (BPA) is under investigation as a possible endocrine disrupter. As an indication of systemic exposure, a fast and accurate assay was developed for the major BPA metabolite in human urine, BPA‐monoglucuronide (BPA‐G), using ultrahigh‐pressure liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS).MethodsUrine samples were prepared using solid‐phase mixed‐mode reversed‐phase/anion‐exchange extraction. BPA‐G was measured using UHPLC/MS/MS with an amide UHPLC column interfaced to a triple‐quadrupole mass spectrometer equipped with negative ion electrospray, collision‐induced dissociation and selected reaction monitoring. [13C12]‐BPA‐G was used as a surrogate standard.ResultsBy measuring the glucuronide metabolite of BPA, potential interference due to BPA contamination from containers, solvents, pipette, etc., was avoided. The standard curve had a linear regression coefficient of 0.999, and the intra‐ and inter‐assay variations were less than 10%. The assay was validated according to FDA guidelines.ConclusionsA fast, accurate, and highly selective method for the determination of BPA‐G in human urine was developed and validated using UHPLC/MS/MS. This method is suitable for assessing human exposure to BPA. Copyright © 2016 John Wiley & Sons, Ltd.
A novel chaos‐based encryption algorithm over TCP data packet for secure communication
Authors: Çavuşoğlu Ünal , Akgül Akif , Kaçar Sezgin , Pehli̇van İhsan , Zengi̇n Ahmet 
Published: January 2016

AbstractIn this article, a new algorithm that can encrypt data on TCP data segment by using a novel chaotic random number generator was developed. First of all, dynamic analyses of the chaotic system to be used were made and the original pseudo‐random number generator (PRNG) with a new approach was designed. Key series produced by PRNG was tested on NIST and passed all the tests. The chaos‐based encryption here was performed on TCP, one of the most fundamental protocols in data communication. Following this, TCP data segments were encrypted by the sender on bit base with key series produced by PRNG, and then they were decrypted by the receiver. Security level of the chaos‐based encryption carried out here was tested with histogram, its key length, key sensitivity and entropy method. Memory and time usages were measured in performance analysis. So as to reveal the performance of the encryption, memory usage, encryption and decryption times were analyzed by comparison on different security algorithms. According to tests and analyses results, this chaos‐based encryption has a high level of performance and security; and it is an original study that can be used in real‐time implementations with TCP protocol. Copyright © 2016 John Wiley & Sons, Ltd.
Concise Review: Paracrine Role of Stem Cells in Pituitary Tumors: A Focus on Adamantinomatous Craniopharyngioma
Authors: Martinez-Barbera Juan Pedro , Andoniadou Cynthia L. 
Published: January 2016

AbstractThe existence of tissue-specific progenitor/stem cells in the adult pituitary gland of the mouse has been demonstrated recently using genetic tracing experiments. These cells have the capacity to differentiate into all of the different cell lineages of the anterior pituitary and self-propagate in vitro and can therefore contribute to normal homeostasis of the gland. In addition, they play a critical role in tumor formation, specifically in the etiology of human adamantinomatous craniopharyngioma, a clinically relevant tumor that is associated with mutations in CTNNB1 (gene encoding β-catenin). Mouse studies have shown that only pituitary embryonic precursors or adult stem cells are able to generate tumors when targeted with oncogenic β-catenin, suggesting that the cell context is critical for mutant β-catenin to exert its oncogenic effect. Surprisingly, the bulk of the tumor cells are not derived from the mutant progenitor/stem cells, suggesting that tumors are induced in a paracrine manner. Therefore, the cell sustaining the mutation in β-catenin and the cell-of-origin of the tumors are different. In this review, we will discuss the in vitro and in vivo evidence demonstrating the presence of stem cells in the adult pituitary and analyze the evidence showing a potential role of these stem cells in pituitary tumors.
Performance of ultrasound‐based endometriosis staging system (UBESS) for predicting level of complexity of laparoscopic surgery for endometriosis
Authors: Menakaya U. , Reid S. , Lu C. , Bassem G. , Infante F. , Condous G. 
Published: January 2016

ABSTRACTObjectiveTo develop and assess the performance of a preoperative ultrasound‐based endometriosis staging system (UBESS) to predict the level of complexity of laparoscopic surgery for endometriosis.MethodsThis was a multicenter prospective and retrospective cohort study on consecutive women with suspected endometriosis who underwent laparoscopy between June 2009 and July 2013. Each woman underwent a systematic transvaginal ultrasound evaluation to assess the pelvis for different phenotypes of endometriosis, and the diagnostic performance of ultrasound for these different phenotypes was evaluated relative to the gold standard, laparoscopy. A three‐stage preoperative UBESS was developed to assess the severity of pelvic endometriosis, based on the histological phenotypes of endometriosis, the anatomical locations of deep infiltrating endometriosis and their sonographic markers of local invasiveness. The three stages of UBESS (I–III) were then correlated with the three levels of complexity of laparoscopic surgery for endometriosis described by the Royal College of Obstetricians and Gynaecologists (Levels 1–3). The end‐points were the diagnostic performance of UBESS to predict the level of complexity of laparoscopic surgery for endometriosis, i.e. UBESS stage I to predict Level‐1 laparoscopic surgery, UBESS stage II to predict Level‐2 laparoscopic surgery and UBESS stage III to predict Level‐3 laparoscopic surgery.ResultsThe analysis included 192 women, with a mean ± SD age at diagnosis of endometriosis of 23.7 ± 9.3 years and a mean duration of symptoms prior to presentation of 42 months. Predominant reported locations of pelvic pain were left iliac fossa (32%), right iliac fossa (29.5%) and lower abdomen (61%) and predominant symptoms included dyspareunia (57.5%), dysmenorrhea (58.5%) and dyschezia (41.5%). The accuracy, sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of UBESS I for predicting a requirement for Level‐1 laparoscopic surgery were: 87.5%, 83.3%, 91.7%, 90.9%, 84.6%, 10 and 0.182; those of UBESS II for predicting Level‐2 surgery were: 87.0%, 73.7%, 90.3%, 65.1%, 93.3%, 7.6 and 0.292; and those of UBESS III for predicting Level‐3 surgery were: 95.3%, 94.8%, 95.5%, 90.2%, 97.7%, 21.2 and 0.054, respectively.ConclusionUBESS could be utilized to predict the level of complexity of laparoscopic surgery for endometriosis. It has the potential to facilitate the triage of women with suspected endometriosis to the most appropriate surgical expertise required for laparoscopic endometriosis surgery. UBESS needs to be validated externally in multiple centers to assess its general applicability. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
“Be Prepared if I Bring It Up:” Patients’ Perceptions of the Utility of Religious and Spiritual Discussion During Genetic Counseling
Authors: Thompson Amanda Bartenbaker , Cragun Deborah , Sumerau J. E. , Cragun Ryan T. , De Gifis Vanessa , Trepanier Angela 
Published: January 2016

AbstractAs debates continue about the relevance of religion to health care, research is needed to guide decisions about whether genetic counselors (GCs) should routinely address religious and/or spiritual (R/S) issues with their patients. We conducted an online survey to gauge patient perspectives on this issue. Among the 70 respondents, frequencies of closed‐ended responses and thematic analyses of open‐ended responses revealed multiple patient concerns related to R/S discussions with GCs. Although 60 respondents reported being R/S, only a small minority would want to discuss R/S issues if it meant less time discussing medical information. Most respondents also expressed opinions that: 1) genetic counseling should be about science; 2) GCs are not qualified to discuss R/S issues; 3) other outlets are available to meet the needs of patients who want R/S counseling; and/or 4) R/S discussions are more likely to be acceptable if patients broach the topic or in specific circumstances (e.g., when patients are facing end‐of life issues). Overall, responses suggest routine or comprehensive R/S assessments or discussions are not necessary and that GCs would be best equipped to help all their patients if they were prepared to listen, be supportive, and make referrals when R/S issues arise in clinic.
Hybrid Mafic Dykes from Delwara Shear Zone, Mt. Abu, NW India
Authors: Pandit Manoj K. , Dotzler Ramona , De Wall Helga 
Published: January 2016

Abstract:
Mafic dykes intrude the composite Mt. Abu granite batholith as a minor and the last phase of magmatism. The dykes are sub-vertical, variable in width and visibly compact, however, features of alteration and shearing can be seen. The dykes occurring within the recently identified and described, Delwara Shear Zone (DWSZ), from the western margin of the Mt. Abu batholith are intensely to moderately sheared and intricately mixed with the host granitoids. The mafic dykes occurring within the shear zone bear evidence of assimilating the host granitoids during their ascent, seen as relicts, streaks and sub-rounded K-feldspar clasts in mafic dykes. The hybridization has resulted in unusual geochemical signatures of the mafic dykes such as higher silica levels, erratic and high incompatible trace element abundances and lack of any systematic trends. Mixing line calculations on the mafic dyke samples reveal between 30 to 60% felsic input into the mafic dykes. Mafic dykes outside the shear zone in the Mt. Abu are meter scale in width and generally free of felsic inclusions owing to small volumes of mafic melts. Large volume of mafic melts are required for assimilating up to 60% felsic component which has been identified as approximately 100 m wide zone within the DWSZ. Shearing has played an important role in providing the channel ways and for sustained high temperatures to allow such hybridization.
Hydrogeochemical Investigation and Qualitative Assessment of Surface Water Resources in West Bokaro Coalfield, India
Authors: Tiwari Ashwani Kumar , Singh Prasoon Kumar , Mahato Mukesh Kumar 
Published: January 2016

Abstract:
A hydrogeochemical study of surface water of the West Bokaro coalfield has been undertaken to assess its quality and suitability for drinking, domestic and irrigation purposes. For this purpose, fourteen samples collected from rivers and ponds of the coalfield were analysed for pH, conductivity, total dissolved solids (TDS), major cations (Ca2+ Mg2+, Na+ and K+), major anions (HCO3-, F-, Cl-, SO42- and NO3-) and trace metals. The pH of the analysed water samples varied from 7.3 to 8.2, indicating slightly alkaline in nature. The electrical conductivity (EC) value varied from 93 μs cm-1 to 906 μs cm-1 while the TDS varied from 76 mg L-1 to 658 mg L-1. HCO3- and SO42- are the dominant anion and Ca2+ and Na+ the cation in the surface water. The concentration of alkaline earth metals (Ca2+ + Mg2+) exceed the alkali metals (Na+ + K+) and HCO3- dominates over SO42- + Cl- concentrations in the majority of the surface water samples. Ca2+ -Mg2+ -HCO3- and Ca2+ -Mg2+ -Cl- are the dominant hydrogeochemical facies in the surface water of the area. The water chemistry is mainly controlled by rock weathering with secondary contribution from anthropogenic sources. For quality assessment, analyzed water parameter values compared with Indian and WHO water quality standard. In majority of the samples, the analyzed parameters are well within the desirable limits and water is potable for drinking purposes. However, concentrations of TDS, TH, Ca2+, Mg2+ and Fe are exceeding the desirable limits in some water samples and needs treatment before its utilization. The calculated parameters such as sodium absorption ration, percent sodium, residual sodium carbonate, permeability index and magnesium hazard revealed good to permissible quality and suitable for irrigation purposes, however, higher salinity, permeability index and Mg-ratio restrict its suitability for irrigation at few sites.
Prediction of the Collapsing Risk of Mining Slopes Based on Geostatistical Interpretation of Geotechnical Parameters
Authors: Khakestar Marzieh Shademan , Hassani Hossein , Moarefvand Parvizz , Madani Hassan 
Published: January 2016

Abstract:
Almost all collapses of rock slopes especially in open pit mines are related to discontinuities such as bedding planes, faults and major joints. Geostatistical assessments can be used for understanding the distribution of regionalized variables in any spatial study. In this paper3D spatial dispersion of the fault planes in the Gole Gohar open pit iron mine, located in Kerman province, south east of Iran, is modeled. Then, regionalized variable theory is used to analyze and interpret spatial distribution of the following geotechnical parameters: Geological strength index (GSI), Rock quality designation (RQD), Cohesion (C) and angle of internal friction (ϕ). In order to define regionalized variable distribution, variogram functions were determined for identifying the regional behavior. Structural analysis of variograms showed that the mentioned parameters have spatial structures that make it possible to set up a geostatistical model to predict their values for each non-sampled block on the pit wall. Results showed that there is a relation between the low values of geotechnical parameters and the existence of discontinuities around the pit area. The role of discontinuities in the occurrence of collapses in the area was clearly demonstrated by comparing the estimated parameters models and the model of discontinuities dispersion.