bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting human hepatic clearance from in vitro drug metabolism and transport data: a scientific and pharmaceutical perspective for assessing drug–drug interactions
Authors: Camenisch Gian , Umehara Ken‐ichi 
Published: March 2012

ABSTRACTObjectivesMembrane transporters and metabolism are major determinants of the hepatobiliary elimination of drugs. This work investigates several key questions for drug development. Such questions include which drugs demonstrate transporter‐based clearance in the clinic, and which in vitro methods are most suitable for drug classification, i.e. transporter‐ vs metabolism‐dependent compound class categories. Additional questions posed are: what is the expected quantitative change in exposure in the presence of a transporter‐ and/or metabolism‐inhibiting drug, and which criteria should trigger follow‐up clinical drug–drug interaction studies.MethodsA well‐established method for (human) liver clearance prediction that considers all four physiological processes driving hepatic drug elimination (namely sinusoidal uptake and efflux, metabolism and biliary secretion) was applied. Suspended hepatocytes, liver microsomes and sandwich‐cultured hepatocytes were used as in vitro models to determine the individual intrinsic clearance for 13 selected compounds with various physicochemical and pharmacokinetic properties.ResultsUsing this in vitro–in vivo extrapolation method a good linear correlation was observed between predicted and reported human hepatic clearances. Linear regression analysis revealed much improved correlations compared with other prediction methods.ConclusionsThe presented approach serves as a basis for accurate compound categorization within the Biopharmaceutics Drug Disposition Classification System (BDDCS) and was applied to anticipate metabolism‐ and transporter‐based drug–drug interactions using different static prediction methods. A decision tree proposal is provided and helps to guide clinical studies on active processes influencing hepatic elimination. All recommendations in this paper are generally intended to support early pre‐clinical and clinical drug development and the filing of a new drug application. Copyright © 2012 John Wiley & Sons, Ltd.
Synthesis of Porous Zinc Gallate Prisms Composed of Highly Oriented Nanoparticles by an In Situ Conversion Reaction
Authors: Zhou Wenli , Yang Xianfeng , Huang Lin , Wang Jing , Tang Jinke , Liang Hongbin 
Published: March 2012

AbstractPorous ZnGa2O4 prisms assembled by highly oriented nanoparticles have been fabricated by an in situ chemical conversion approach. We report, for the first time, that a solid α‐Ga2O3 precursor can be directly converted into ZnGa2O4 rather than through the intermediate GaOOH. Based on a detailed study of the evolution of ZnGa2O4 prisms, a growth mechanism is proposed for the in situ conversion reaction. During this conversion process, the precursor morphology can be highly retained, which is attributed to the similar atomic arrangements of the Ga and O atoms and excellent matching of the lattice spacing between the α‐Ga2O3 and ZnGa2O4 prisms. The direct reaction between the precursor α‐Ga2O3 and Zn2+ ions is more efficient than that between the byproduct GaOOH and Zn2+ ions. Moreover, the photoluminescent color of the ZnGa2O4 phosphor can be tuned by doping with Mn2+ ions. Efficient energy transfer (ET) from the host lattice to the Mn2+ centers is observed, whereas ET from the defects to the Mn2+ ions is prohibited. The fabricated ZnGa2O4 products have potential in the field of display applications.
Nanoscale channel engineered double gate MOSFET for mixed signal applications using high‐k dielectric
Authors: Nirmal D , Vijayakumar P , Shruti K , Mohankumar N 
Published: March 2012

ABSTRACTFinFETs (fin field effect transistors) are used for complementary‐symmetry metal–oxide–semiconductor applications beyond the 45‐nm node of the SIA roadmap because of their excellent scalability and better immunity to short channel effects. However, FinFETs having channel lengths below 100 nm show considerable leakage current and threshold voltage roll‐off. To overcome these effects, a channel engineering technique is introduced. A single halo (SH) FinFET is developed using Sentaurus simulator, and its analog performance is investigated. The device performance is analysed by replacing the gate dielectric silicon dioxide with various high dielectric constant (k) materials, and it is observed that the integration of high‐k dielectrics in the devices significantly reduces the short channel effects and leakage current. The suitability of nanoscale SH FinFETs for circuit applications is observed with the help of an inverter circuit, and their gain values are calculated for circuit applications. Copyright © 2012 John Wiley & Sons, Ltd.
Locoregional failure and the risk of distant metastasis after modern radiotherapy for head and neck cancer
Authors: Dragovic Aleksandar F. , Caudell Jimmy J. , Spencer Sharon A. , Carroll William R. , Nabell Lisle A. , Bonner James A. 
Published: March 2012

AbstractBackgroundEvolving epidemiology and improvements in locoregional therapy necessitate reassessment of the relationship between locoregional failure and distant metastasis in squamous cell carcinoma of the head and neck (SCCHN).MethodsRetrospective assessments of factors associated with distant metastasis‐free survival were made for 560 patients with SCCHN who received definitive radiotherapy (RT) +/− concurrent systemic therapy at our institution between 1995 and 2007.ResultsFifty‐six patients (10.0%) developed distant metastasis. Three‐year actuarial locoregional control and distant metastasis‐free survival were 72% and 87%, respectively. Multivariate analysis revealed N classification and locoregional failure as significant predictors of reduced distant metastasis‐free survival (p< .001). In patients with distant metastasis detected after locoregional failure, the mean interval between these events was 11.6 months.ConclusionLocoregional failure may play a causative role for distant metastasis in some patients with SCCHN, suggesting a need for continued focus on improving locoregional therapies. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Prospective change control analysis of transfer of platelet concentrate production from a specialized stem cell transplantation unit to a blood transfusion center
Authors: Sigle Joerg‐Peter , Medinger Michael , Stern Martin , Infanti Laura , Heim Dominik , Halter Joerg , Gratwohl Alois , Buser Andreas 
Published: March 2012

AbstractBackground and objectives: Specialized centers claim a need for blood component production independent from the general blood transfusion services. We performed a prospective change control analysis of the transfer of platelet (PLT) production for hematological patients at the University Hospital Basel from the Department of Hematology to the Blood Transfusion Centre, Swiss Red Cross, Basel in February 2006. We wanted to demonstrate that neither quality nor transfusion outcome was affected. Material and methods: Production quantity and efficiency, product quality and transfusion outcome were systematically recorded. A 2‐year pretransfer period was compared to a 2 year post‐transfer period. Results: After transfer production quantity at the Blood Transfusion Centre increased from 4,483 to 6,190 PLT concentrates. Production efficiency increased with a significant decrease in the rate of expired products (18% vs. 8%; P < 0.001). Product quality showed a slight decrease in median PLT count per unit (2.84 vs. 2.75 × 1011; P < 0.001) and a slight increase in mean storage time prior to transfusion (3.18 vs. 3.30 days; P < 0.001). Transfusion outcome measured as median corrected count increment one hour post‐transfusion (10.5 vs. 10.7; P = 0.3) and the rate of patients with inadequate post‐transfusion increment (31.5% vs. 32.1%; P = 0.6) did not differ. Conclusion: Supply and quality of PLT products was maintained after the transfer of PLT production to the Blood Transfusion Centre. An optimization of the supply chain process with markedly decreased expiration rates was achieved. These results argue against the need of specialized PLT production sites for selected patient groups. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc.
Feasibility of semi‐quantitative assessment of left ventricular contractile reserve in dilated cardiomyopathy
Authors: Otasevic Petar , Tasic Nebojsa , Vidakovic Radoslav , Boskovic Srdjan , Radak Djordje , Djukanovic Bosko , Angelkov Lazar , Kostic Nada , Caparevic Zorica , Vasiljevic‐Pokrajcic Zorana 
Published: March 2012

AbstractBackground:We and others have shown previously that left ventricular (LV) contractile reserve assessed quantitatively by high‐dose dobutamine stress‐echocardiography (DSE) has prognostic implications in patients with dilated cardiomyopathy.Purpose:To assess the feasibility of semi‐quantitative assessment of LV contractile reserve by differently skilled operators in patients with dilated cardiomyopathy.Methods:High‐dose DSE was performed in 63 consecutive patients, mean age 50 ± 10 years and ejection fraction (EF) 19 ± 8%. LVEF was calculated 1) using Simpson's biplane formula, and 2) semi‐quantitatively (5% increments) by novice and experienced echocardiographers, and by a DSE expert. Patients were considered to have preserved LV contractile reserve if LVEF dobutamine‐induced change was ≥5%.Results:Twenty‐seven (45.8%) patients died during the 5‐year follow‐up. The feasibility of the assessment was 89%, 94%, and 98% for novice and experienced readers and DSE expert, respectively. Kaplan‐Meier analysis showed that LV contractile reserve assessed semi‐quantitatively by DSE expert and experienced reader achieved the best prognostic separation (log rank 19.63 and 18.99, respectively, p < 0.001 for both), followed by quantitative assessment (log rank 9.76, p = 0.0018) and assessment by novice reader (log rank 8.76, p = 0.012). Areas under the curves were similar for quantitative and semi‐quantitative assessment of LV contractile reserve.Conclusions:Our data indicate that semi‐quantitative assessment of LV contractile reserve is feasible by differently skilled operators. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound 40:405–409, 2012
Degenerative process and cell death in salivary glands of Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae) semi‐engorged female exposed to the acaricide permethrin
Authors: Nodari Elen Fernanda , Roma Gislaine Cristina , Furquim Karim Christina Scopinho , De Oliveira Patrícia Rosa , Bechara Gervásio Henrique , Camargo‐Mathias Maria Izabel 
Published: March 2012

AbstractTicks are ectoparasites of great medical and veterinary importance around the world and synthetic chemicals such as permethrin have been used for their control. This study provides a cytochemistry analysis of both degenerative and cell death processes in salivary glands of the brown dog tick Rhipicephalus sanguineus semi‐engorged females exposed to 206, 1,031, and 2,062 ppm of permethrin. The results presented herein demonstrate that permethrin is a potent chemical acaricide that would act on the glandular tissue's morphophysiology in this tick species by eliciting severe changes in the acinus shape, intense vacuolation of the acinar cells' cytoplasm, marked glandular tissue disorganization, culminating in an advanced degenerative stage with consequent formation of many apoptotic bodies (cell death). In addition, permethrin induced major changes in the acinar cells' nucleus, such as a change both in its shape and size, chromatin marginalization, nuclear fragmentation, and appearance of picnotic nuclei, especially when the highest concentrations of the product were used. Thus, permethrin induced early degeneration of this tissue characterized by significant changes in the structure of acinar cells and production of enzymes related to the cell death process, in addition to interfering directly in the genetic material of these cells. Microsc. Res. Tech. 75:1012–1018, 2012. © 2012 Wiley Periodicals, Inc.
Path: Ways Typology has Walked Through it
Authors: Imbert Caroline 
Published: March 2012

AbstractThis paper deals with the expression of space in linguistic typology, more specifically with Path encoding. The term “Path” refers to the path followed by an entity with respect to another: for instance, in a scene where a cat runs and a table stands, Path will refer to the cat running past the table, below the table, down from the table, etc. The literature on how Path is encoded in different languages is abundant. This paper is not an exhaustive state‐of‐the‐art review of the literature. It rather intends to guide the reader through major recent landmarks that would help one understand how typological generalizations about Path expression have been attained, what are such generalizations and how part of them still constitute an issue.
Dynamic lot sizing with all‐units discount and resales
Authors: Li Chung‐Lun , Ou Jinwen , Hsu Vernon N. 
Published: March 2012

AbstractWe consider a single‐product dynamic lot‐sizing model with an all‐units quantity discount pricing scheme available to the buyer, where the discount price breakpoints are stationary. To capture the real‐life behavior of a typical buyer who often takes advantage of quantity discounts through purchasing in excess of the anticipated demand, our model allows the buyer to resell or dispose of any leftover inventory that he/she does not need. We show that the general problem with an arbitrary number of discount price breakpoints is NP‐hard. We then develop a polynomial algorithm for the problem with an O(Tm+3) running time when the number of price breakpoints, m, is fixed, where T is the number of time periods in the planning horizon. We further develop an O(T2) algorithm for the special case with a single price breakpoint. © 2012 Wiley Periodicals, Inc. Naval Research Logistics, 2012
Improved algorithms for a lot‐sizing problem with inventory bounds and backlogging
Authors: Hwang Hark‐Chin , van den Heuvel Wilco 
Published: March 2012

AbstractThis article considers a dynamic lot‐sizing problem with storage capacity limitation in which backlogging is allowed. For general concave procurement and inventory costs, we present an O(T2) dynamic programming algorithm where T is the length of the planning horizon. Furthermore, in case of a fixed‐charge cost structure without speculative motives, we show that the problem can be solved in O(T) time. By carefully choosing decompositions of the problems, we can use classical results like an efficient matrix searching algorithm and geometric techniques to achieve the results. © 2012 Wiley Periodicals, Inc. Naval Research Logistics, 2012
Equilibrium analysis of capacity allocation with demand competition
Authors: Liu Zhixin 
Published: March 2012

AbstractThis article examines the capacity allocation decisions in a supply chain in which a supplier sells a common product to two retailers at a fixed wholesale price. The retailers order the supplier's product subject to an allocation mechanism preannounced by the supplier, and compete for the customer demand. We perform an equilibrium analysis of the retailers' ordering decisions under uniform and individually responsive allocations. Uniform allocation guarantees equilibrium orders, but is not necessarily truth inducing in the presence of demand competition. Further, we find that (1) neither the supplier nor either one of the retailers sees its profits necessarily increasing with the supplier's capacity, and the supplier may sell more with a lower capacity level, and (2) capacity allocation may not only affect the supply chain members' profits but also change the supply chain structure by driving a retailer out of the market. This article provides managerial insights on the capacity and ordering decisions for the supplier, the retailers, and the supply chain. © 2012 Wiley Periodicals, Inc. Naval Research Logistics, 2012
Transformation of macromonomers into ring‐opening polymerization macroinitiators: A detailed initiation efficiency study
Authors: Zorn Anna‐Marie , Barner‐Kowollik Christopher 
Published: March 2012

AbstractIn the present study, n‐butyl acrylate macromonomer (BAMM) (Mn = 1900 g mol−1; PDI = 1.96) has been synthesized via a high‐temperature polymerization process. Subsequently, the olefinic termini of the BAMM have been transformed into a diol via a dihydroxylation process using KMnO4 as an oxidizing agent. The OH‐terminated macroinitiator pBA(OH)2 has subsequently been employed for the ring‐opening polymerization (ROP) of ε‐caprolactone via various catalytic systems, that is, organo‐(1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene), metal (tin(II) 2‐ethylhexanoate), and enzymatic catalysis (Novozym® 435). The obtained pBA‐b‐pCL block copolymers and the initiation efficiency of the BAMM macroinitiator have been investigated via size exclusion chromatography (SEC), electrospray ionization–mass spectrometry (ESI‐MS) hyphenated with SEC and liquid chromatography at the critical conditions of both poly(ε‐caprolactone) (pCL) and pBA. The in vitro enzyme catalysis (eROP) approach proved to be the most efficient catalysis system due to minor transesterification side reactions during the polymerization process. However, side reactions such as transesterifications occur in each catalytic system and—while they cannot be suppressed—they can be minimized. The species generated during the eROP process include the desired block copolymer pBA‐b‐pCL as main species as well as pCL homopolymer and residual macroinitiator pBA(OH)2. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Humidity dependent properties of a transparent conducting film doped with BEDO‐TTF complex
Authors: Yamochi Hideki , Haneda Tsuyoshi , Tracz Adam , Saito Gunzi 
Published: March 2012

AbstractConducting reticulate doped polymer (RDP) films with transparent appearance were prepared by the two‐step method. Polycarbonate films were doped with the bis(ethylenedioxy)tetrathiafulvalene (BEDO‐TTF) complex of ${\rm ReO}_{{\rm 4}}^{- } $, Br−, ${\rm C(CN)}_{{\rm 3}}^{- } $, or ${\rm C}_{{\rm 2}} {\rm O}_{{\rm 4}}^{{\rm 2}- } $, the surface resistivities of which were 1.5, 1.4, 30, and 8.0 kΩ/□, respectively. The films containing ${\rm ReO}_{{\rm 4}}^{- } $ and Br− complexes showed quasi‐reversible humidity dependent behaviors, in which the resistivity and inter‐conducting‐layer distance were increased and decreased, respectively, in dry atmosphere. The ReO4 containing film exhibited better reversibility, while the existence of two kinds of crystal structures was proved for the Br complex. magnified image
The effect of barrier strain on the reliability of Inx Al1–xN/AlN/GaN heterostructure field‐effect transistors
Authors: Kayis Cemil , Ferreyra Romualdo A. , Zhu Congyong , Avrutin Vitaliy , Özgür Ümit , Morkoç Hadis 
Published: March 2012

AbstractWe report on the reliability of Inx Al1–xN/AlN/GaN‐based heterostructure field‐effect transistors (HFETs) fabricated on five different wafers with varying indium compositions (0.12 ≤ x ≤ 0.20) encompassing the tensile/compressive strain fields. All of the tested devices underwent high field on‐state stress at 20 V DC drain bias and zero gate bias for five hours. We monitored the drain current and low‐frequency noise (LFN) a priori and a posteriori the stress treatment to quantify device degradation. HFETs suffering tensile strain showed remarkably large degradation which manifested itself with up to 25 dB increase in noise power and up to 72% loss of drain current after stress. On the other hand, devices fabricated on compressively strained structures remained intact after stress, but they had about 30 dB higher pre‐stress noise‐power levels and about 50% lower drain‐current densities to begin with. The results show that the nearly lattice‐matched In0.17Al0.83N barrier exhibited very low degradation along with current density remaining high compared with the devices having barriers with lower or higher indium content. Our results suggest that the nearly‐lattice‐matched InAlN can be a good candidate for devices due to its relatively better reliability while maintaining a high current density. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Mechanism of the aerobic oxidation of methanol to formic acid on Au8−: A DFT study
Authors: Karanjit Sangita , Bobuatong Karan , Fukuda Ryoichi , Ehara Masahiro , Sakurai Hidehiro 
Published: March 2012

AbstractThe mechanism of the aerobic oxidation of methanol to formic acid catalyzed by Au8− has been systematically investigated using density functional theory with the M06 functional. The reaction pathways were examined by taking into account the full structural relaxation of the Au8−. Stepwise and concerted reaction mechanisms are proposed. The stepwise mechanism is initiated by the hydrogen abstraction of a methoxy species by a superoxo‐like anion on the gold cluster, resulting in the formation of formaldehyde. Subsequently, the formaldehyde is activated by the hydroxyl group of a hydroperoxyl‐like complex, leading to the formation of a hemiacetal intermediate. The formation of formic acid in the final step is achieved by hydrogen abstraction of the hemiacetal intermediate by atomic oxygen attached to the gold cluster. Our calculations indicate that the first step of the stepwise mechanism, that is, hydrogen abstraction of the methoxy species, is the rate‐determining step. Another possible reaction pathway involving a single‐step hydrogen abstraction, a concerted mechanism, is also discussed. This mechanism may also be responsible for the reasonable catalytic activity of aerobic oxidation of methanol on Au8− because of the low activation energy barrier. © 2012 Wiley Periodicals, Inc.
Preoperative Treatment Does Not Improve the Therapeutic Results of Abdominosacral Amputation of the Rectum
Authors: Bębenek Marek , Tupikowski Wiesław , Cisarż Karol , Balcerzak Alicja , Wojciechowski Leszek , Stankowska Anna , Tarkowski Radosław 
Published: March 2012

AbstractBackgroundThis study reviewed the impact of preoperative chemoradiotherapy/short‐term radiotherapy on abdominosacral amputations of the rectum (ASAR) for the treatment of low‐rectum cancers in terms of postoperative morbidity, local recurrence rates, and survival.MethodsA total of 198 patients with stage II and III tumors located within 6 cm of the anorectal junction underwent ASAR between 1998 and 2008 and were selected for further analysis. Patients were compared according to the following groups: those who had surgery only (Group A) and those who had preoperative chemoradiotherapy/short‐term radiotherapy (Group B).ResultsThere were 44 and 154 patients in Groups A and B, respectively, including 135 males. The median age of the subjects was 63 years (range = 35–88). The median follow‐up period was 81 months (range = 23–138). Neither the local recurrence rates (6.8% in Group A vs. 4.6% in Group B, p = 0.544) nor the 5‐year relative survival rates (72.4% in Group A vs. 69.3% in Group B, p = 0.127) differed significantly between the groups.ConclusionPreoperative therapy in low‐rectum cancer does not improve the therapeutic results of ASAR.