bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potencies of vitamin D analogs, 1α‐hydroxyvitamin D3, 1α‐hydroxyvitamin D2 and 25‐hydroxyvitamin D3, in lowering cholesterol in hypercholesterolemic mice in vivo
Authors: Quach Holly P. , Dzekic Tamara , Bukuroshi Paola , Pang K. Sandy 
Published: February 2018

AbstractVitamin D3 and the synthetic vitamin D analogs, 1α‐hydroxyvitamin D3 [1α(OH)D3], 1α‐hydroxyvitamin D2 [1α(OH)D2] and 25‐hydroxyvitamin D3 [25(OH)D3] were appraised for their vitamin D receptor (VDR) associated‐potencies as cholesterol lowering agents in mice in vivo. These precursors are activated in vivo: 1α(OH)D3 and 1α(OH)D2 are transformed by liver CYP2R1 and CYP27A1 to active VDR ligands, 1α,25‐dihydroxyvitamin D3 [1,25(OH)2D3] and 1α,25‐dihydroxyvitamin D2 [1,25(OH)2D2], respectively. 1α(OH)D2 may also be activated by CYP24A1 to 1α,24‐dihydroxyvitamin D2 [1,24(OH)2D2], another active VDR ligand. 25(OH)D3, the metabolite formed via CYP2R1 and or CYP27A1 in liver from vitamin D3, is activated by CYP27B1 in the kidney to 1,25(OH)2D3. In C57BL/6 mice fed the high fat/high cholesterol Western diet for 3 weeks, vitamin D analogs were administered every other day intraperitoneally during the last week of the diet. The rank order for cholesterol lowering, achieved via mouse liver small heterodimer partner (Shp) inhibition and increased cholesterol 7α‐hydroxylase (Cyp7a1) expression, was: 1.75 nmol/kg 1α(OH)D3 > 1248 nmol/kg 25(OH)D3 (dose ratio of 0.0014) > > 1625 nmol/kg vitamin D3. Except for 1.21 nmol/kg 1α(OH)D2 that failed to lower liver and plasma cholesterol contents, a significant negative correlation was observed between the liver concentration of 1,25(OH)2D3 formed from the precursors and liver cholesterol levels. The composite results show that vitamin D analogs 1α(OH)D3 and 25(OH)D3 exhibit cholesterol lowering properties upon activation to 1,25(OH)2D3: 1α(OH)D3 is rapidly activated by liver enzymes and 25(OH)D3 is slowly activated by renal Cyp27b1 in mouse.
Cytochrome P450 2C9‐natural antiarthritic interactions: Evaluation of inhibition magnitude and prediction from in vitro data
Authors: Tan Boon Hooi , Ahemad Nafees , Pan Yan , Palanisamy Uma Devi , Othman Iekhsan , Yiap Beow Chin , Ong Chin Eng 
Published: February 2018

AbstractMany dietary supplements are promoted to patients with osteoarthritis (OA) including the three naturally derived compounds, glucosamine, chondroitin and diacerein. Despite their wide spread use, research on interaction of these antiarthritic compounds with human hepatic cytochrome P450 (CYP) enzymes is limited. This study aimed to examine the modulatory effects of these compounds on CYP2C9, a major CYP isoform, using in vitro biochemical assay and in silico models. Utilizing valsartan hydroxylase assay as probe, all forms of glucosamine and chondroitin exhibited IC50 values beyond 1000 μM, indicating very weak potential in inhibiting CYP2C9. In silico docking postulated no interaction with CYP2C9 for chondroitin and weak bonding for glucosamine. On the other hand, diacerein exhibited mixed‐type inhibition with IC50 value of 32.23 μM and Ki value of 30.80 μM, indicating moderately weak inhibition. Diacerein's main metabolite, rhein, demonstrated the same mode of inhibition as diacerein but stronger potency, with IC50 of 6.08 μM and Ki of 1.16 μM. The docking of both compounds acquired lower CDOCKER interaction energy values, with interactions dominated by hydrogen and hydrophobic bondings. The ranking with respect to inhibition potency for the investigated compounds was generally the same in both in vitro enzyme assay and in silico modeling with order of potency being diacerein/rhein > various glucosamine/chondroitin forms. In vitro‐in vivo extrapolation of inhibition kinetics (using 1 + [I]/Ki ratio) demonstrated negligible potential of diacerein to cause interaction in vivo, whereas rhein was predicted to cause in vivo interaction, suggesting potential interaction risk with the CYP2C9 drug substrates.
Hypothesis tests for stratified mark‐specific proportional hazards models with missing covariates, with application to HIV vaccine efficacy trials
Authors: Sun Yanqing , Qi Li , Yang Guangren , Gilbert Peter B. 
Published: February 2018

AbstractThis article develops hypothesis testing procedures for the stratified mark‐specific proportional hazards model with missing covariates where the baseline functions may vary with strata. The mark‐specific proportional hazards model has been studied to evaluate mark‐specific relative risks where the mark is the genetic distance of an infecting HIV sequence to an HIV sequence represented inside the vaccine. This research is motivated by analyzing the RV144 phase 3 HIV vaccine efficacy trial, to understand associations of immune response biomarkers on the mark‐specific hazard of HIV infection, where the biomarkers are sampled via a two‐phase sampling nested case‐control design. We test whether the mark‐specific relative risks are unity and how they change with the mark. The developed procedures enable assessment of whether risk of HIV infection with HIV variants close or far from the vaccine sequence are modified by immune responses induced by the HIV vaccine; this question is interesting because vaccine protection occurs through immune responses directed at specific HIV sequences. The test statistics are constructed based on augmented inverse probability weighted complete‐case estimators. The asymptotic properties and finite‐sample performances of the testing procedures are investigated, demonstrating double‐robustness and effectiveness of the predictive auxiliaries to recover efficiency. The finite‐sample performance of the proposed tests are examined through a comprehensive simulation study. The methods are applied to the RV144 trial.
Sensitive and selective detection of Cu(II) ion: A new effective 1,8‐naphthalimide‐based fluorescence ‘turn off’ sensor
Authors: Huang Guozhen , Li Chuang , Han Xintong , Aderinto Stephen Opeyemi , Shen Kesheng , Mao Shanshan , Wu Huilu 
Published: February 2018

AbstractThe present study reports the development of a new 1,8‐naphthalimide‐based fluorescent sensor V for monitoring Cu(II) ions. The sensor exhibited pH independence over a wide pH range 2.52–9.58, and indicated its possible use for monitoring Cu(II) ions in a competitive pH medium. The sensor also showed high selectivity and sensitivity towards the Cu(II) ions over other competitive metal ions in DMSO–HEPES buffer (v/v, 1:1; pH 7.4) with a fluorescence ‘turn off’ mode of 79.79% observed. A Job plot indicated the formation of a 1:1 binding mode of the sensor with Cu(II) ions. The association constant and detection limit were 1.14 × 106 M–1 and 4.67 × 10–8 M, respectively. The fluorescence spectrum of the sensor was quenched due to the powerful paramagnetic nature of the Cu(II) ions. Potential application of this sensor was also demonstrated when determining Cu(II) ion levels in two different water samples.
Characterization of imatinib mesylate formulations distributed in South American countries: Determination of genotoxic impurities by UHPLC–MS/MS and dissolution profile
Authors: Wolff Fernanda Caroline , Dillenburg Thaís Luise , Venzon Antunes Marina , Linden Rafael , Comparsi Wagner Sandrine , Verza Simone G. 
Published: February 2018

AbstractImatinib mesylate (IM) is an anti‐neoplasic drug used for the treatment of cancer. Recent new guidelines specify daily doses and concentration limits for genotoxic impurities (GTIs) in pharmaceutical final products. Therefore, in this work an analytical method using UHPLC–MS/MS was developed, validated and applied to characterize IM tablets for two GTIs: N‐(2‐methyl‐5‐aminophenyl)‐4‐(3‐pyridyl)‐2‐pyrimidine amine (Imp. 1), and N‐[4‐methyl‐3‐(4‐methyl‐3‐yl‐pyrimidin‐2‐ylamino)‐phenyl]‐4‐ chloromethyl benzamide (Imp. 2), simultaneously. Additionally, dissolution data of IM tablets were compared using a methodology recommended by the US Food and Drug Administration. The UHPLC method utilized an Acquity BEH C18 (150 × 2.1 mm, 1.7 μm) maintained at 40°C. The mobile phase consisted of ammonium formate 0.063% (phase A) and acetonitrile plus 0.05% formic acid (phase B) in gradient elution. A sensitive method for determination of previously mentioned GTIs in IM tablets was successfully developed and applied. Overall, the formulations analyzed in this work showed low levels of Imp. 1 and Imp. 2. However, the sample named D1 showed very high levels of Imp. 1 and failed to meet the requirements established by the US Food and Drug Administration for dissolution data. Periodic verification of GTIs in pharmaceutical formulations is important to minimize safety risks, so analytical methods to determine it need be available and implemented in routine analysis.
Characteristics of paramedian pontine arteries disease and its association with hemoglobinA1c
Authors: Li Haiyan , Shu Yaqing , Hu Biao , Dai Yongqiang , Lin Yinyao , Shan Yilong , Wang Yuge , Cai Wei , Lu Zhengqi 
Published: February 2018

AbstractObjectivesThe association of branch atherosclerotic disease (BAD) and diabetes mellitus (DM) in the territory of posterior circulation is rarely discussed. Intracranial BAD was divided into two different types: paramedian pontine arteries (PPA) disease (PPD) and lenticulostriate arteries (LSA) disease. The goal of the study was to evaluate the clinical characteristics of PPD and its association with hemoglobinA1c (HbA1c) in China.Materials and MethodsRadiologically confirmed PPD was defined as an isolated unilateral infarction extending to the ventral surface of the pons. Small deep cerebral infarctions are usually caused by two different pathological changes of arteries: BAD and lipohyalinotic degeneration (LD). We compared the vascular risk factors between BAD and LD in PPA territory. A total of 159 stroke patients were analyzed (PPD, n = 75; LD, n = 84). Patients with PPD were also categorized into two groups according to follow‐up modified Rankin Scale (FmRS) scores. Logistic regression analyses were used for the evaluation of independent risk factors of PPD and prognosis.ResultsComparison between PPD and LD revealed statistical significance in fasting glucose, HbA1c, estimated glomerular filtration rate (eGFR), and uric acid (p = .011, p = .005, p = .027, p = .018, respectively). Compared with LD, PPD was only related to HbA1c (p = .011) in logistic regression analysis. There were statistically significant differences between the two groups based on the stratification of FmRS scores in fasting glucose, HbA1c, homocysteine, eGFR, and the occurrence of DM. After multivariate analysis, only HbA1c was related with poor prognosis of PPD (p = .002).ConclusionsThe subtypes and prognosis of small deep brain infarcts are significantly influenced by elevated HbA1c level in PPA territory. DM might play an important role in the pathogenesis of PPD.
Low‐cost educational resource using optical fibers to send 4‐bit images in grayscale
Authors: Rivera‐Ortega Uriel , Martinez‐Sisniega Nilli , Alcantara‐Mendoza Uriel 
Published: February 2018

AbstractOptical fibers are widely used in different areas, such as industry, research, and education, just to mention a few. Due to this fact, their applications are commonly included in undergraduate engineering programs or in related fields of education. In this article, a new low‐cost educational resource for a better understanding and a practical application of optical fibers is proposed. The main purpose of this resource is to send 4‐bit images in grayscale through optical fibers with a laser diode and receive it with a photoresistor, with a total estimated setup‐cost of fifteen dollars. The setup includes a visual user‐interface programmed with the software LabVIEW, which lets to select and prepare an image for a proper sending. The same program is in charge of applying different intensities for each type of bit through a generic laser diode and of receiving the information back, all done with the aid of an Arduino Uno board, which serves as the electric interface.
Quantum Crystallography: Current Developments and Future Perspectives
Authors: Genoni Alessandro , Bučinský Lukas , Claiser Nicolas , Contreras‐García Julia , Dittrich Birger , Dominiak Paulina M. , Espinosa Enrique , Gatti Carlo , Giannozzi Paolo , Gillet Jean‐Michel , Jayatilaka Dylan , Macchi Piero , Madsen Anders Ø. , Massa Lou , Matta Chérif F. , Merz Kenneth M. , Nakashima Philip N. H. , Ott Holger , Ryde Ulf , Schwarz Karlheinz , Sierka Marek , Grabowsky Simon 
Published: February 2018

AbstractCrystallography and quantum mechanics have always been tightly connected because reliable quantum mechanical models are needed to determine crystal structures. Due to this natural synergy, nowadays accurate distributions of electrons in space can be obtained from diffraction and scattering experiments. In the original definition of quantum crystallography (QCr) given by Massa, Karle and Huang, direct extraction of wavefunctions or density matrices from measured intensities of reflections or, conversely, ad hoc quantum mechanical calculations to enhance the accuracy of the crystallographic refinement are implicated. Nevertheless, many other active and emerging research areas involving quantum mechanics and scattering experiments are not covered by the original definition although they enable to observe and explain quantum phenomena as accurately and successfully as the original strategies. Therefore, we give an overview over current research that is related to a broader notion of QCr, and discuss options how QCr can evolve to become a complete and independent domain of natural sciences. The goal of this paper is to initiate discussions around QCr, but not to find a final definition of the field.
Activation of Acetonitrile with (C2F5)3PF2 and Amines
Authors: Bader Julia , Neumann Beate , Stammler Hans‐Georg , Ignat'ev Nikolai , Hoge Berthold 
Published: February 2018

AbstractAcetonitrile is deprotonated by a combination of the strong Lewis acid (C2F5)3PF2 and triethylamine. The resulting cyanomethyl function is bound to the phosphorus moiety, affording the highly stable salt [HNEt3][P(C2F5)3F2(CH2CN)]. Salt metathesis reactions furnished the corresponding [Cu(MeCN)2]+ and [Ag(MeCN)]+ derivatives in which the CH2CN substituent of the anion [P(C2F5)3F2(CH2CN)]− coordinates to the metal. An investigation of the gas separation capability of the silver salt [Ag(MeCN)][P(C2F5)3F2(CH2CN)] shows an uptake of 1.7 equivalents of isobutene from a propane/isobutene mixture. The reaction of (C2F5)3PF2 with acetonitrile and diethylamine furnishes [P(C2F5)3F2{NHC(CH3)NEt2}]—a phosphate featuring an amidine ligand which formally results from hydroamination of acetonitrile by HNEt2. Exchange of HNEt2 with the primary amines H2NPh and H2NBu leads to comparable amidine salts that exhibit a solvent‐dependent conformational isomerism.
Carbon Nanotubes Encapsulated in Coiled‐Coil Peptide Barrels
Authors: Mann Florian A. , Horlebein Jan , Meyer Nils Frederik , Meyer Daniel , Thomas Franziska , Kruss Sebastian 
Published: February 2018

AbstractSpecific functionalization of 1D nanomaterials such as near infrared (nIR) fluorescent single‐walled carbon nanotubes (SWCNTs) is essential for colloidal stability and tailoring of their interactions with the environment. Here, we show that de novo designed alpha‐helical coiled‐coil peptide barrels (αHBs) with appropriate pores encapsulate and solubilize SWCNTs. In contrast, barrels without or with narrow pores showed a much smaller efficiency. Absorption/fluorescence spectroscopy and atomic force microscopy indicate that the SWCNTs are incorporated into the αHB′s pore. The resulting hybrid SWCNT@αHBs display periodic surface coverage with a 40 nm pitch and remain fluorescent in the nIR. This approach presents a novel concept to encapsulate, discriminate and functionalize SWCNTs non‐covalently with peptides and holds great promise for future applications in bioimaging or drug delivery.
Zwerge mit leuchtender Zukunft
Authors: Haufe Helfried , Böttcher Horst 
Published: February 2018

ZusammenfassungDer Übersichtsartikel berichtet über die aktuelle Forschung und Entwicklung von graphitischen Kohlenstoff‐Nanopartikeln (engl. Graphitic Carbon dots) insbesondere im Hinblick auf ihre Synthese und die Möglichkeiten ihrer chemischen und biomedizinischen Nutzung. Als eine neue Kategorie von Nanomaterialien zeigen Kohlenstoff‐Nanopartikel eine Reihe besonderer Eigenschaften: einstellbare Photolumineszenz bis in den infraroten Spektralbereich, hohe Biokompatibilität, geringe Toxizität, hohe chemische Stabilität und gute Wasserlöslichkeit. Graphitische Kohlenstoff‐Nanopartikel können durch einfache, grüne, kostengünstige Synthesen aus nahezu allen organischen Materialien hergestellt werden. Darüber hinaus können die physikalisch‐chemischen Eigenschaften und das Photolumineszenzverhalten sowohl durch Oberflächenpassivierung und – funktionalisierung als auch durch Modifizierung mit Fremdatomen gesteuert werden. Seit ihrer Entdeckung im Jahr 2004 wurden zahlreiche Anwendungsmöglichkeiten in der chemischen Sensorik, in der biomedizinischen Diagnostik und Therapie und in der Photokatalyse gefunden, die sehr vielversprechend für zukünftige Entwicklungen sind.
Einweg‐Bioreaktoren
Authors: Eibl Regine , Jossen Valentin , Eibl Dieter 
Published: February 2018

ZusammenfassungEinweg‐Bioreaktoren sind in der Entwicklung und Produktion von monoklonalen Antikörpern angekommen. Studien belegen, dass sie richtig ausgewählt und eingesetzt sicherere, schnellere, grünere und kleinere Produktionsverfahren als ihre wiederverwendbaren Gegenspieler erlauben und zu Kosteneinsparungen beitragen. In der Inokulumproduktion haben sich wellendurchmischte Einweg‐Bioreaktoren durchgesetzt, während die Anwender in der Fermentation mehrheitlich mit gerührten Einweg‐Bioreaktoren arbeiten. Es wird prognostiziert, dass die Anzahl der Einweg‐Bioreaktoren weiter zunehmen wird.
Catalytic Enantioselective Simultaneous Control of Axial Chirality and Central Chirality in Allenes
Authors: Dai Jianxin , Duan Xinyu , Zhou Jing , Fu Chunling , Ma Shengming 
Published: February 2018

AbstractChiral molecules, which may contain one or more different type(s) of stereocentres, such as central, axial, planar, and helical chiralities, etc., are indispensable in chemistry, pharmaceutical industry, and life science. Despite many advances for the preparation of chiral molecules usually with a single type of chirality have been realized, simultaneous construction of different types of chiralities is still a significant challenge. Here, we wish to report a protocol for preparation of chiral allenes with both central and axial chiralities via a catalytic asymmetric allenylation of different biologically or synthetically useful fluorinated or non‐fluorinated nucleophiles with readily available racemic allenes by using a single chiral ligand. An echoing between the central chirality and axial chirality for the enantioselectivity was observed. This strategy provides a general and practical approach to functionalized optically active allenes bearing both central and axial chiralities with an excellent enantioselectivity under mild conditions.
Confirmation of the Cardiac Safety of PGF2αReceptor Antagonist OBE022 in a First‐in‐Human Study in Healthy Subjects, Using Intensive ECG Assessments
Authors: Täubel Jörg , Lorch Ulrike , Coates Simon , Fernandes Sara , Foley Paul , Ferber Georg , Gotteland Jean‐Pierre , Pohl Oliver 
Published: February 2018

AbstractOBE022, a new orally active prostaglandin F2α receptor antagonist (OBE022) with myometrial selectivity is being developed to reduce uterine contractions during preterm labor. This first‐in‐human study evaluated the effect of OBE022 following multiple doses on the QT interval in 23 healthy postmenopausal women, using the effect of a meal on QTc to demonstrate assay sensitivity. We report the cardiac safety outcome performed during the multiple ascending part of this trial. OBE022 was administered after a standardized breakfast on day 1 and in the fasted state from day 3 to day 9 wth a standardized lunch 4 hours after administration. Concentration–effect modeling was used to assess the effect of prodrug OBE022 and parent OBE002 on QTc after a single dose (days 1 and 3) and multiple doses (day 9). The concentration–response analysis showed the absence of QTc prolongation at all doses tested. Two‐sided 90% confidence intervals of the geometric mean Cmax for estimated QTc effects of OBE022 and OBE002 of all dose groups were consistently below the threshold of regulatory concern. The sensitivity of this study to detect small changes in the QTc was confirmed by a significant shortening of the QTc on days 1, 3, and 9 after standardized meals. This study establishes that neither prodrug OBE022 nor parent OBE002 prolong the QTc interval. The observed food effect on the QT interval validated the assay on all assessment days. Both the change from predose, premeal and the change from premeal, postdose demonstrated the specificity of the method.
DTM@GPU: Characterizing and evaluating trace redundancy in GPU
Authors: J. Marzulo Leandro A. , C. Sena Alexandre , S. Nery Alexandre , Bentes Cristiana , M. Coelho Igor , S. de Castro Maria Clicia , T. Oliveira Saulo , A. O. Alves Tiago , M. G. França Felipe 
Published: February 2018

SummaryIn a program, there is usually a significant amount of instructions that are repeatedly executed with the same inputs during the execution. This redundancy allows the reuse of previous computations, potentially reducing the program execution time. The Dynamic Trace Memoization technique (DTM) was proposed to exploit the reuse of a dynamic sequence of redundant instructions for superscalar CPUs. This paper proposes the application of the DTM technique on a GPU architecture. We propose the DTM@GPU model that adapts the original DTM technique to the NVIDIA GPU architecture by introducing architectural modifications and the identification of different trace reuse styles in multithreaded environments. We investigate reuse opportunities in real‐world GPU applications and the potential performance gains. We also perform a detailed investigation on the characteristics of the reused traces. This characterization shows the number and size of the reused traces, the influence of the cache size on reuse rates, and the cycles that are saved when all threads in a warp reuse instructions or traces. The results show approximately up to 35.3% of reuse, yielding an estimated speedup gain of 10.7%.
Automated generation of reference dynamical models for constrained robotic systems in the presence of friction and damping effects
Authors: Jarzębowska Elżbieta , Augustynek Krzysztof , Urbaś Andrzej 
Published: February 2018

SummaryThis paper details a new automated generation method of dynamic models of structures allowing presence of friction and damping in their models as well as subjected to position or kinematic constraints. The constraints may be material, which come from the system interaction with environment, or may be programmed. The novelty of the presented dynamics generation method is to include friction and damping into modeling and to require predefined constraint satisfaction as well. The latter requirement is critical, since when friction and damping are neglected, controllers may be inadequately designed, constraints may be violated, and overall system performance may be poor. The developed method is applied to a manipulator model, whose end‐effector performance is predefined by programmed constraints. Simulation results present manipulator constrained motion. The advantage of this method is that it serves both reference and control oriented dynamics derivation, and the final dynamics models are obtained in the reduced state form, ie, constraint reaction forces are eliminated. This is the fundamental difference between the presented approach and the Lagrange based approaches to constrained system modeling.