bluuebunny/crossref_metadata_2025 huggingface dataset:
A Remarkable cis‐ and trans‐Spanning Dibenzylidene Acetone Diphosphine Chelating Ligand (dbaphos)
Authors: Jarvis Amanda G. , Sehnal Petr E. , Bajwa Somia E. , Whitwood Adrian C. , Zhang Xiangbiao , Cheung Man Sing , Lin Zhenyang , Fairlamb Ian J. S.
Published: March 2013

A multidentate and flexible diolefin–diphosphine ligand, based on the dibenzylidene acetone core, namely dbaphos (1), is reported herein. The ligand adopts an array of different geometries at Pt, Pd and Rh. At PtII the dbaphos ligand forms cis‐ and trans‐diphosphine complexes and can be defined as a wide‐angle spanning ligand. 1H NMR spectroscopic analysis shows that the β‐hydrogen of one olefin moiety interacts with the PtII centre (an anagostic interaction), which is supported by DFT calculations. At Pd0 and RhI, the dbaphos ligand exhibits both olefin and phosphine interactions with the metal centres. The Pd0 complex of dbaphos is dinuclear, with bridging diphosphines. The complex exhibits the coordination of one olefin moiety, which is in dynamic exchange (intramolecular) with the other “free” olefin. The Pd0 complex of dbaphos reacts with iodobenzene to afford trans‐[PdII(dbaphos)I(Ph)]. In the case of RhI, dbaphos coordinates to form a structure in which the phosphine and olefin moieties occupy both axial and equatorial sites, which stands in contrast to a related bidentate olefin, phosphine ligand (“Lei” ligand), in which the olefins occupy the equatorial sites and phosphines the axial sites, exclusively.
Versatile Supramolecular Cross‐Linker: A Rotaxane Cross‐Linker That Directly Endows Vinyl Polymers with Movable Cross‐Links
Authors: Arai Takayuki , Jang Keumhee , Koyama Yasuhito , Asai Shigeo , Takata Toshikazu
Published: March 2013

A supramolecular cross‐linked cross‐linker, capable of introducing rotaxane cross‐links to vinyl polymers, has been developed for the rational synthesis of polyrotaxane networks. The experimental results reveal that the combination of an oligocyclodextrin (OCD) and a terminal bulky group‐tethering macromonomer (TBM) forms a polymer‐network structure having polymerizable moieties through supramolecular cross‐linking. Radical polymerization of a variety of typical vinyl monomers in the presence of the vinylic supramolecular cross‐linker (VSC) afforded the corresponding vinyl polymers cross‐linked through the rotaxane cross‐links (RCP) as transparent stable films in high yields under both photoinitiated and thermal polymerization conditions. A poly(N,N‐dimethylacrylamide)‐based hydrogel synthesized by using VSC, RCPDMAAm, displayed a unique mechanical property. The small‐angle X‐ray scattering (SAXS) results, indicating patterns characteristic of a polyrotaxane network, clearly suggested the presence and role of the rotaxane cross‐links. The confirmation of the introduction of rotaxane‐cross‐links into vinyl polymers strongly reveals the significant usefulness of VSC.
Sedimentary Records of Evolution of Heavy Metals in Songhua Lake, Northeast China
Authors: Hao Libo , Sun Liji , Zhao Yuyan , Lu Jilong
Published: March 2013

In this paper, the vertical variations of heavy metal elements (including Cd, Cr, Cu, Hg, Mn, Ni, Pb, and Zn) in the sediments of Songhua Lake are analyzed using sediment cores. A 70‐year evolutionary history of these heavy metal elements in Songhua Lake is described and the sources of the heavy metals in the sediments are investigated by evaluating the pollution characteristics of the metals in terms of their enrichment coefficients and geoaccumulation indexes. The results indicate that Cr, Cu, Mn, Ni, Pb, and Zn in the sediments originated mainly from basin erosion and were transported to the lake by rivers. Cd and Hg in the sediments also originated from basin erosion that occurred prior to the mid‐1990s, and these sediments have since been overlaid by artificial pollution. The distribution of heavy metals in the sediments of Songhua Lake is influenced by many factors, including sediment composition, the relative importance of fluvial input, and artificial pollution.
Simultaneous Determination of 11 Sulfonamides by HPLC–UV and Application for Fast Screening of Their Aerobic Elimination and Biodegradation in a Simple Test
Authors: Mahmoud Waleed M. M. , Khaleel Nareman D. H. , Hadad Ghada M. , Abdel‐Salam Randa A. , Haiß Annette , Kümmerer Klaus
Published: March 2013

Sulfonamides (SAs) are one of the most frequently used antibiotics. SAs have been found in various environmental compartments. If SAs are not degraded in the environment, they can affect bacteria by their antibiotic properties and contribute to bacterial antibiotic resistance. Therefore, the biodegradability of 11 SAs (sulfanilamide, sulfaguanidine monohydrate, sulfadiazine, sulfathiazole, sulfapyridine, sulfamerazine, sulfamethoxypyridazine, sulfachloropyridazine, sulfamethazine, sulfamethoxazole, and sulfadimethoxine) was studied. For this purpose, the Closed Bottle Test (CBT, OECD 301D) was performed, which includes a toxicity control. In order to monitor the environmental fate of the parent compound and to check for transformation products, a simple, efficient, and reliable HPLC–UV method for the simultaneous determination of these SAs has been developed. Acetonitrile and water (with 0.1% formic acid) were used as mobile phase solvents for gradient elution. The method was validated in terms of precision, detection and quantitation limits, selectivity, and analytical solution stability. In the CBT, none of these SAs was readily biodegradable. The HPLC–UV analysis confirmed that no degradation of any SA took place. In the toxicity control, these SAs showed no toxic effect in the used concentration of environmental bacteria applied in the test.
Effect of the Organic Matter to Ammonia Ratio on Aerobic Granulation during 4‐Chlorophenol Degradation in a Sequencing Batch Reactor
Authors: Arellano‐Badillo Víctor Manuel , Moreno‐Andrade Iván , Buitrón Germán
Published: March 2013

The influence of the chemical oxygen demand (COD)/N ratio on the performance of a granular sequencing batch reactor (SBR) system degrading 4‐chlorophenol (4CP) was evaluated. Two SBR were operated under the same conditions, but with two different COD/N ratios, 150 and 20. It was observed that successful granule formation was obtained when activated sludge was initially acclimated to 4CP without using a co‐substrate, and then hydrodynamic pressure selection was used to generate granules. Removal efficiencies of 4CP were >99.7%, and the specific degradation rates were up to 87 mg 4CP/(mg volatile suspended solid) per hour. It was found that nitrogen limitation had no effect on the removal efficiencies of 4CP and on the specific degradation rates. However, the results indicated that under nitrogen‐limited conditions, higher granule sizes and a denser biomass were promoted.
Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women
Authors: Gamba Christina A. , Swetter Susan M. , Stefanick Marcia L. , Kubo Jessica , Desai Manisha , Spaunhurst Katrina M. , Sinha Animesh A. , Asgari Maryam M. , Sturgeon Susan , Tang Jean Y.
Published: March 2013

BACKGROUND:

Nonsteroidal anti‐inflammatory drugs (NSAIDs) have been associated with decreased risk of gastric, colorectal, and breast cancer. However, the impact of NSAIDs on the risk of melanoma has been inconsistent. The authors evaluated the association between NSAID use and cutaneous melanoma risk in the Women's Health Initiative (WHI) Observational Study (OS).

METHODS:

At study entry, use of aspirin (acetylsalicylic acid [ASA]) and nonaspirin NSAIDs was assessed among 59,806 postmenopausal Caucasian women ages 50 to 79 years. Cox proportional hazards models were constructed after adjusting for participant skin type, sun exposure history, and medical indications for NSAID use among other confounders.

RESULTS:

During a median follow‐up of 12 years, 548 incident melanomas were confirmed by medical review. Women who used ASA had a 21% lower risk of melanoma (hazard ratio, 0.79; 95% confidence interval, 0.63‐0.98) relative to nonusers. Increased duration of ASA use (<1 year, 1‐4 years, and ≥5 years) was associated with an 11% lower risk of melanoma for each categorical increase (Ptrend = .01), and women with ≥5 years of use had a 30% lower melanoma risk (hazard ratio, 0.70; 95% confidence interval, 0.55‐0.94). In contrast, use of non‐ASA NSAIDs and acetaminophen were not associated with melanoma risk.

CONCLUSIONS:

Postmenopausal women who used ASA had a significantly lower risk of melanoma, and longer duration of ASA use was associated with greater protection. Although this study was limited by the observational design and self‐report of NSAID use, the findings suggest that ASA may have a chemopreventive effect against the development of melanoma and warrant further clinical investigation. Cancer 2013. © 2012 American Cancer Society.
Foldings and grazings of tori in current controlled interleaved boost converters
Authors: Giaouris Damian , Banerjee Soumitro , Stergiopoulos Fotis , Papadopoulou Simira , Voutetakis Spyros , Zahawi Bashar , Pickert Volker , Abusorrah Abdullah , Al Hindawi Mohammed , Al‐Turki Yusuf
Published: March 2013

Interleaved boost converters (IBCs) are used when energy conversion is required at high current levels. Such converter systems may undergo various nonlinear phenomena which can affect their performance adversely. In this paper, we study an IBC and demonstrate the first instability through a Neimark–Sacker bifurcation, resulting in a torus. An analysis based on the calculation of the monodromy matrix reveals that the torus has a rather strange form as the complex Floquet multipliers that became unstable have a real value close to −1. We show that further variation in a parameter can result in novel nonlinear phenomena where the torus itself folds and grazes a switching manifold, resulting in a ‘wobbling’ of the closed loop that represents the torus in discrete time. Numerical and analytical results validate our work. Copyright © 2013 John Wiley & Sons, Ltd.
Generation of mice with a conditional Lbh null allele
Authors: Lindley Linsey E. , Briegel Karoline J.
Published: March 2013

Limb bud and heart (LBH) is a developmentally expressed, tissue‐specific transcription cofactor in vertebrates that acts in the WNT signaling pathway, a genetic program critical for embryogenesis and adult tissue homeostasis. Aberrant gain‐of‐function of LBH is implicated in both human congenital disease and cancer. The normal physiological function of LBH has remained elusive owing to a lack of genetic loss‐of‐function models. Here, we have generated mice with a conditional null allele of Lbh by flanking exon 2 with loxP sites (Lbhflox). Homozygous Lbhflox and LbhloxP mice, in which the Neo cassette was removed through FLPe‐mediated recombination, were viable and fertile, indicating that these conditional Lbh alleles are fully functional. LbhloxP mice were then crossed with a Rosa26‐Cre line, resulting in ubiquitous deletion of exon 2 and abolishment of LBH protein expression. Mice homozygous for the Lbh null allele (LbhΔ2) displayed normal embryonic development and postnatal growth with morphologies indistinguishable from wild‐type littermates. However, mammary gland development, which occurs primarily after birth, was perturbed. Thus, the conditional Lbh allele will be a valuable tool to uncover the currently unknown tissue‐specific roles of LBH in postnatal development and disease. genesis 51:491–497. © 2013 Wiley Periodicals, Inc.
IMprinting of PAthogenic Memory in Berlin
Authors: Romagnani Chiara , Hauser Anja , Chang Hyun‐Dong
Published: March 2013

Immunological memory is not only protective against recurrent pathogens but it also contributes to the pathogenesis of chronic inflammation, especially in rheumatic diseases. The Joint Meeting of the Henry Kunkel Society (HKS) and the Research Consortium IMPAM (IMprinting of the PAthogenic Memory for rheumatic inflammation), which took place in June 2012 in Berlin, was devoted to discussing the basic mechanisms involved in the generation and maintenance of immunological memory, as well as the implications of immunological memory for the pathogenesis and therapy of rheumatic diseases, cancer and vaccine development as outlined in this Meeting Report.
Analytical modelling and performance evaluation of realistic time‐controlled M2M scheduling over LTE cellular networks
Authors: Gotsis Antonis G. , Lioumpas Athanasios S. , Alexiou Angeliki
Published: March 2013

Supporting emerging machine‐to‐machine (M2M) communications over Long‐term Evolution (LTE)/LTE Advanced cellular networks in an efficient way will be beneficial for both telecommunication communities. The first step to migrate to an M2M‐enabled cellular standard is to provide these new services through the existing architectures and protocols, while maintaining seamless backward compatibility. To this end, we thoroughly examined a key LTE Medium Access Control entity, which is the packet scheduler, and proposed solutions based on the time‐controlled M2M feature, to deal with the diverse M2M traffic characteristics and quality‐of‐service requirements. Starting from the single M2M class case, we extended our study to more realistic scenarios, involving more M2M classes with diverse quality‐of‐service requirements. We defined analytical models for predicting the system performance on the basis of queueing theory concepts and considered the interaction between classes with different priorities. The proposed analytical models are validated through extensive system‐level simulations. On the basis of the insight obtained from our analytical approach, we modified an existing scheduling algorithm to improve the performance of low‐priority M2M device groups, and we demonstrated its superior performance both experimentally and analytically. Copyright © 2013 John Wiley & Sons, Ltd.
Atmospheric Δ14C reduction in simulations of Atlantic overturning circulation shutdown
Authors: Matsumoto Katsumi , Yokoyama Yusuke
Published: March 2013

A rapid reduction in the Atlantic meridional overturning circulation (AMOC) can significantly disrupt the global heat transport and likely triggered abrupt climate change during the last glacial cycle. A slowdown in AMOC has long been assumed to inhibit the exchange of carbon between the atmosphere and the deep ocean and thus cause radiocarbon (14C), which is produced in the atmosphere, to accumulate in the atmosphere. Indeed previous model studies have demonstrated that a reduction in AMOC leads to higher atmospheric 14C abundance (Δ14C). However, this seems inconsistent with the observed rise in atmospheric pCO2 during Heinrich 1 and the Younger Dryas stadial events and the emerging view that this CO2 rise resulted from the deep ocean venting “old” carbon. Using an Earth system model, we offer an alternative scenario that AMOC slowdown and an accompanying dynamical response in the south (i.e., the bipolar seesaw) can in fact lead to a decline in atmospheric Δ14C. This decline is realized in the model when the bipolar seesaw and thus the flux of old carbon from the Southern Ocean are sufficiently large so as to overcome the accumulation of 14C in the atmosphere as AMOC is reduced. The bipolar seesaw we describe invokes an oceanic teleconnection, whereby a freshwater perturbation in the North Atlantic drives a southern Δ14C response, but this does not necessarily preclude an atmospheric teleconnection.
Hydrological sensitivity to greenhouse gases and aerosols in a global climate model
Authors: Kvalevåg Maria Malene , Samset Bjørn H. , Myhre Gunnar
Published: March 2013

Changes in greenhouse gases and aerosols alter the atmospheric energy budget on different time scales and at different levels in the atmosphere. We study the relationship between global mean precipitation changes, radiative forcing, and surface temperature change since preindustrial times caused by several climate change components (CO2, CH4, sulphate and black carbon (BC) aerosols, and solar forcing) using the National Center for Atmospheric Research Community Earth System Model (CESM1.03). We find a fast response in precipitation due to atmospheric instability that correlates with radiative forcing associated with atmospheric absorption and a slower response caused by changes in surface temperature which correlates with radiative forcing at the top of the atmosphere. In general, global climate models show large differences in climate response to global warming, but here we find a strong relationship between global mean radiative forcing and global mean precipitation changes that is very consistent with other models, indicating that precipitation changes from a particular forcing mechanism are more robust than previously expected. In addition, we look at the precipitation response and relate it to changes in lifetime of atmospheric water vapor (τ). BC aerosols have a significantly larger impact on changes in τ related to surface temperature compared to greenhouse gases, sulphate aerosols, and solar forcing and are the dominating forcing mechanism affecting fast precipitation in this quantity.
Observations of enhanced nonlinear instability in the surface reflection of internal tides
Authors: Xie Xiaohui , Shang Xiaodong , van Haren Hans , Chen Guiying
Published: March 2013

Enhanced vertically standing waves formed by the superposition of two upward and downward going near‐diurnal (D1) waves are observed during one semidiurnal (D2) spring tide in an approximately 75 day long velocity record from the northeastern South China Sea. Bicoherence estimates suggest that the enhanced D1 waves are likely due to nonlinear parametric subharmonic instability of D2 internal tides. The timescale for energy growth by an order of magnitude is about 2.5 days for these waves. In addition to subharmonics, higher harmonics D4 (=D2 + D2) and a mean flow are generated by a different nonlinear interaction during the same D2 spring tide. The separation of coherent from incoherent internal tidal signals and a rotary spectral decomposition in the vertical direction reveal that D2 waves with opposite vertical propagation directions in the region of internal tide reflection from the surface may be responsible for the pronounced nonlinear instability.
Could the collision of CMEs in the heliosphere be super‒elastic? Validation through three‒dimensional simulations
Authors: Shen Fang , Shen Chenglong , Wang Yuming , Feng Xueshang , Xiang Changqing
Published: March 2013

Though coronal mass ejections (CMEs) are magnetized fully ionized gases, a recent observational study of a CME collision event in 2008 November has suggested that their behavior in the heliosphere is like elastic balls, and their collision is probably superelastic [C. Shen et al., 2012]. If this is true, this finding has an obvious impact on the space weather forecasting because the direction and velocity of CMEs may change. To verify it, we numerically study the event through three‒dimensional MHD simulations. The nature of CMEs' collision is examined by comparing two cases. In one case, the two CMEs collide as observed, but in the other, they do not. Results show that the collision leads to extra kinetic energy gain by 3–4% of the initial kinetic energy of the two CMEs. It firmly proves that the collision of CMEs could be superelastic.
The influence of migrating bed forms on the velocity‐intermittency structure of turbulent flow over a gravel bed
Authors: Keylock Christopher J. , Singh Arvind , Foufoula‐Georgiou Efi
Published: March 2013

Modeling turbulent flows at high Reynolds number requires solving simplified variants of the Navier‐Stokes equations. The methods used to close the resulting Reynolds‐averaged, or eddy simulation equations usually follow classical theory and, at small enough scales, postulate universal scaling for turbulence that is independent of the velocity itself. This may not be the best way to conceptualize geophysical turbulence. Turbulent intermittency may be defined in terms of the local “roughness” of the velocity signal as measured by pointwise Hölder exponents. This study investigates the joint velocity‐intermittency structure of flow over a gravel‐bed surface with migrating bed forms. We report clear velocity‐intermittency dependence and quantify its nature above the moving bed form profile. Our results imply differences in energy transfer close to bed forms at shorter wavelengths than those forced directly. Hence, progress in modeling flows of geophysical relevance may require a reconsideration of the principles on which turbulence closures are based.
Climate models without preindustrial volcanic forcing underestimate historical ocean thermal expansion
Authors: Gregory J.M. , Bi D. , Collier M.A. , Dix M.R. , Hirst A.C. , Hu A. , Huber M. , Knutti R. , Marsland S.J. , Meinshausen M. , Rashid H.A. , Rotstayn L.D. , Schurer A. , Church J.A.
Published: March 2013

Episodic explosive volcanic eruptions are a natural part of the climate system but are often omitted from atmosphere‐ocean general circulation model (AOGCM) preindustrial spin‐up and control experiments. This omission imposes a negative bias on ocean heat uptake in simulations of the historical period. In models of a range of complexity, we find that global‐mean sea level rise due to thermal expansion during the last ∼ 150 years is consequently underestimated by 5–30 mm, which is a substantial proportion of the model mean of 50 mm in Coupled Model Intercomparison Project Phase 3 AOGCMs with anthropogenic forcing only, and is therefore important in accounting for 20th century sea level rise. We test and recommend a procedure for removing the bias.
Long Noncoding RNAs Associated With Liver Regeneration 1 Accelerates Hepatocyte Proliferation During Liver Regeneration By Activating Wnt/β-Catenin Signaling
Authors: Xu Dan , Yang Fu , Yuan Ji-hang , Zhang Ling , Bi Hai-shan , Zhou Chuan-chuan , Liu Feng , Wang Fang , Sun Shu-han
Published: March 2013

In recent years, long noncoding RNAs (lncRNAs) have been investigated as a new class of regulators of biological function. A recent study reported that lncRNAs control cell proliferation in hepatocellular carcinoma (HCC). However, the role of lncRNAs in liver regeneration and the overall mechanisms remain largely unknown. To address this issue, we carried out a genome-wide lncRNA microarray analysis during liver regeneration in mice after 2/3 partial hepatectomy (PH) at various timepoints. The results revealed differential expression of a subset of lncRNAs, notably a specific differentially expressed lncRNA associated with Wnt/

β

-catenin signaling during liver regeneration (an lncRNA associated with liver regeneration, termed lncRNA-LALR1). The functions of lncRNA-LALR1 were assessed by silencing and overexpressing this lncRNA

in vitro

and

in vivo

. We found that lncRNA-LALR1 enhanced hepatocyte proliferation by promoting progression of the cell cycle

in vitro

. Furthermore, we showed that lncRNA-LALR1 accelerated mouse hepatocyte proliferation and cell cycle progression during liver regeneration

in vivo

. Mechanistically, we discovered that lncRNA-LALR1 facilitated cyclin D1 expression through activation of Wnt/β-catenin signaling by way of suppression of Axin1. In addition, lncRNA-LALR1 inhibited the expression of Axin1 mainly by recruiting CTCF to the

AXIN1

promoter region. We also identified a human ortholog RNA of lncRNA-LALR1 (lncRNA-hLALR1) and found that it was expressed in human liver tissues.

Conclusion

: lncRNA-LALR1 promotes cell cycle progression and accelerates hepatocyte proliferation during liver regeneration by activating Wnt/β-catenin signaling. Pharmacological intervention targeting lncRNA-LALR1 may be therapeutically beneficial in liver failure and liver transplantation by inducing liver regeneration. (Hepatology 2013;58:739–751)
The rivers of Africa: witness of climate change and human impact on the environment
Authors: Mahe G. , Lienou G. , Descroix L. , Bamba F. , Paturel J. E. , Laraque A. , Meddi M. , Habaieb H. , Adeaga O. , Dieulin C. , Chahnez Kotti F. , Khomsi K.
Published: March 2013

In this paper, we study the impact of climate change on river regimes in several parts of Africa, and we look at the most probable causes of these changes either climatically or anthropogenically driven. We study time series of updated monthly and annual runoff of rivers of North Africa, West Africa (Sahelian and humid tropical regions) and Central Africa, including the largest river basins: Niger and Volta rivers in West Africa, and Congo and Ogooue rivers in Central Africa. The recent years are studied in the perspective of multi‐decadal variability. In West Africa and in a part of Central Africa, the climate has changed since 1970, and rainfall has not returned to previous annual amounts, except in Equatorial Africa. The consequences of the long‐lasting drought are, depending on the area concerned, the modification of seasonal regimes (Equatorial area), the groundwater table decrease (Tropical humid area) and the land cover degradation (Sahelian area). The increasing number of dams and of agricultural areas also plays a major role on the modification of river regimes. The population increase will continue to impact on the environment: land cover change, deforestation, agriculture and increasing number of dams will be associated with a reduction of water and sediment discharges to the sea, and major impacts on downstream ecosystems and coastal areas. It seems necessary to share with stakeholders a comprehensive approach of the water cycle from the basin to the sea, to prevent long‐lasting damages to ecosystems and infrastructures. Copyright © 2013 John Wiley & Sons, Ltd.
Book Reviews
Authors: HUTCHEON DUNCAN E.
Published: March 2013

Book reviewed in this article:

Cardiac Rehabilitation. Lenore R. Zohman and Jerome S. Tobis.

Lewis's Pharmacology, 4th Edition. James Crossland.

The Economics of Drug Innovation. Joseph D. Cooper, editor.

New Aspects of Storage and Release Mechanisms of Catecholamines. H. J. Schumann and G. Kroneberg, editors.

Ocular Anti‐Inflammatory Therapy. Herbert E. Kaufman, editor. Charles C Thomas

Digitalis Intoxication. Edward K. Chung.
Drugs Released for Clinical Use
Authors: de HAEN PAUL
Published: March 2013

This listing includes new single chemical entities and preparations, duplicate single products, and combination products that have been made available for clinical use by the U.S. Food and Drug Administration during the period from July 21 to September 20, 1971. This information is taken from the manufacturer's package insert or brochure, which should be consulted for further details on indications, dosage, contraindications, and adverse reactions.
Drugs Released for Clinical Use
Authors: de HAEN PAUL
Published: March 2013

This listing includes new single chemical entities and preparations, duplicate single products, and combination products that have been made available for clinical use by the U.S. Food and Drug Administration during the period from October 21 to December 20, 1971. This information is taken from the manufacturer's package insert or brochure, which should be consulted for further details on indications, dosage, contraindications, and adverse reactions.
Drugs Released for Clinical Use
Authors: de HAEN PAUL
Published: March 2013

This listing includes new single chemical entities and preparations, duplicate single products, and combination products that have been made available for clinical use by the U.S. Food and Drug Administration during the period January 21 to March 20, 1972. This information is taken from the manufacturer's package insert or brochure, which should be consulted for further details on indications, dosage, contraindications, and adverse reactions.
Book Reviews
Authors: HUTCHEON DUNCAN E.
Published: March 2013

Book reviewed in this article:

The Principles and Practice of Clinical Trials. E. L. Harris and J. D. Fitzgerald

Cardiovascular Dynamics, 3rd Edition. Robert F. Rushmer.
Book Reviews
Authors: PROCITA LEONARD
Published: March 2013

Book reviewed in this article:

Pharmacology and Toxicology of Naturally Occurring Toxins. International Encyclopedia of Pharmacology and Therapeutics. Section 71, Volume II. H. Raskovà

Insulin I: Handbook of Experimental Pharmacology, Volume 32. E. Dorzbach
Elevation of Liver Enzymes in Multiple Dose Trials During Placebo Treatment: Are They Predictable?
Authors: Merz M. , Seiberling M. , Höxter G. , Hölting M. , Wortha H.P.
Published: March 2013

The present study examined the increase in transaminases, especially in ALT in young healthy males during placebo treatment in phase I multiple dose trials. The primary objective was to investigate whether volunteers showing increasing ALT levels also present characteristic patterns of demographic data, laboratory parameters, and vital signs. The secondary objective was to determine whether there is a possibility to predict increases of ALT during a trial by analyzing demographic data and baseline levels of routine safety laboratory parameters and vital signs. In a meta‐analysis of 13 placebo‐controlled multiple dose phase I studies, volunteers showing elevations of ALT during placebo treatment were compared with those presenting no clinically significant changes of ALT levels. Demographic data as well as routine safety laboratory values and vital signs measured at screening and on the first day of the in‐house stay were subject to the analysis. Using Wilcoxon's rank sum test, significant differences between ALT‐susceptibles and ALT‐nonsusceptibles were found for baseline values (mean values of screening and the first day of the in‐house stay) of ALT, γGT, AST/ALT, and AST/γGT. Differences found for the screening values of the heart rate were statistically rather than clinically significant.

Cut‐off values were found for baseline levels of ALT and AST/ALT ratio. Their use resulted in a sensitivity of 73% and a specificity of 74% with regard to predictability of ALT levels increasing during the trial.
Single‐ and Multiple‐Dose Pharmacokinetics of Riluzole in White Subjects
Authors: Liboux Aimé Le , Lefebvre Patricia , Roux Yvonne Le , Truffinet Philippe , Aubeneau Michel , Kirkesseli Stéphane , Montay Guy
Published: March 2013

Riluzole is a novel neuroprotective agent that has been developed for the treatment of amyotrophic lateral sclerosis. A series of studies was undertaken to establish its pharmacokinetics on single‐ and multiple‐dose administration in young white male volunteers. The mean absolute oral bioavailability of riluzole (50‐mg tablet) was approximately 60%. Maximum plasma concentration (Cmax) and area under the concentration—time curve (AUC) values were linearly related to dose for the range studied. Cmax occurred at 1.0 hour to 1.5 hours after administration. Plasma elimination half‐life appeared to be independent of dose. After repeated administration of 100 mg riluzole for 10 days, some intraindividual variability in bioavailability was seen. A high‐fat meal significantly reduced the rate (tmax = 2 hours compared with 0.8 hours; Cmax = 216 ng · mL−1 compared to 387 ng · mL−1) and extent of absorption (AUC = 1,047 ng · hr · mL−1 versus 1,269 ng · hr · mL−1). With multiple‐dose administration, riluzole showed dose related absorption, although the terminal plasma half‐life was prolonged slightly. Steady‐state plasma concentrations were achieved within 5 days. Steady‐state trough plasma concentrations were significantly higher with a 75‐mg dose twice daily than with a 50‐mg dose three times daily, although AUC values did not differ.
Pharmacokinetics of Isosorbide Dinitrate in Healthy Volunteers After 24‐Hour Intravenous Infusion
Authors: Bergami Alessandra , Bernasconi Roberto , Caccia Silvio , Leopaldi Daniele , Mizrahi Jacques , Sardina Marco , Urso Renato , Warrington Steve J. , Latini Roberto
Published: March 2013

No studies have examined the pharmacokinetics of isosorbide dinitrate (ISDN) after infusion of long duration, even though such infusions are used in patients. We therefore measured ISDN and its active metabolites, isosorbide‐5‐mononitrate (IS5MN) and isosorbide‐2‐mononitrate (IS2MN), in plasma of 9 healthy volunteers who received a continuous intravenous infusion of ISDN for 24 hours at a dose rate that lowered diastolic blood pressure by 10% during the first 30 minutes of infusion. All subjects tolerated the infusion except one who experienced intolerable headache. Five subjects received 1 μg · min−1 · kg−1, one 2 μg · min−1 · kg−1, and two 4 μg · min−1 · kg−1 ISDN, whereas the full rate of 6 μg · min−1 · kg−1 was used continuously in one subject. At all infusion rates the plasma concentrations of ISDN were higher at 24 hours than at earlier times, suggesting that a steady‐state condition had not been reached at that time. The same was true for the mononitrate metabolites, which reached higher plasma concentrations and were cleared more slowly than the parent compound after the end of the infusion. Apparent elimination half‐lives of ISDN, IS2MN, and IS5MN were 67 ± 10 minutes, 115 ± 13 minutes, and 272 ± 38 minutes, respectively. Comparison of low‐rate infusions (1 and 2 μg · min−1 · kg−1) with high‐rate infusions (4 and 6 μg · min−1 · kg−1) showed that the plasma concentration ratios at 24 hours of mononitrate metabolites to parent drug and apparent plasma clearance of ISDN were almost halved at the higher infusion rates.
Pharmacokinetics of Fosinoprilat in Chinese and Whites After Intravenous Administration
Authors: Hu Oliver Yoa‐Pu , Ding Philip Y. A. , Huang Christine Shu‐hui , Hwang Giann Ming , Chu Kai‐Min
Published: March 2013

The pharmacokinetics of fosinoprilat was studied in 12 healthy Chinese men after a 7.5 mg intravenous dose of fosinoprilat. The data were compared with those from an earlier study using the same protocol in nine healthy white men.

Blood and urine samples were obtained before and at various time intervals after fosinoprilat administration up to 24 hours and 48 hours, respectively. Pharmacokinetic parameters were calculated by fitting the plasma or serum concentrations to a three‐compartment model. The total clearance (Clt), renal clearance (ClT), and nonrenal clearance (ClNR) were significantly lower in Chinese (16.29 ± 6.92, 6.85 ± 2.97, and 9.44 ± 5.08 mL · hr−1 · kg−1) than those obtained in whites (29.88 ± 6.36, 13.55 ± 3.45, and 16.33 ± 5.07 mL · hr−1 · kg−1)). The Chinese subjects had a significantly lower volume of distribution (Vc [volume of distribution of central compartment] and Vdss [volume of distribution at steady state]) (29.38 ± 21.12 and 73.67 ± 40.20 mL/kg) than white men (58.14 ± 15.01 and 152.49 ± 24.89 mL/kg). The Chinese men also had a shorter elimination half‐life than whites, although not statistically significant. The respective half‐lives in Chinese and whites were 5.51 ± 1.53 and 8.24 ± 4.99 hours. The significant differences in ClNR and ClR may be related to lower liver elimination function and lower kidney excretory function, respectively. Plasma protein binding may contribute to part of the difference in the volume of distribution. Chinese men have smaller volume of distribution and clearances of fosinoprilat after intravenous administration compared with white men. The cumulative urine excretion of fosinoprilat was not different between Chinese and whites. Chinese may require a lower fosinoprilat dosage to obtain plasma concentrations similar to whites after intravenous administration. However, since a relatively high variation was found in fosinopril oral absorption, the oral dosage of fosinopril for Chinese and whites may not be different. Further study is obviously needed to elucidate whether the pharmacodynamic effect may be different between Chinese and whites.
The Interplay of Photophysical Properties in Carbazole Fluorescent Oligomers
Authors: Hsu Chung‐Yi , Hsieh Mu‐Tao , Chen Yen‐Fu , Hsu Chun‐Chia , Hung Tzu‐Lin , Chen Chun‐Shuo , Whang Thou‐Jen
Published: March 2013

The photophysical properties and the organic synthesis using effective palladium‐catalyzed Suzuki coupling reactions from a series of carbazole derivatives are described and the relationships of the donor and acceptor groups are also investigated. The purification of the materials and its applications along with the corresponding photo‐physical characterizations were presented. With the advantages gained from 2D‐COSY spectra, which provide more correlated information between immediate atoms than 1H‐NMR spectra and a series of further investigations were undertaken including powder X‐ray diffraction analysis, Infrared and Raman spectroscopy, constructing the composition conformation and chemical structure of the materials is more easily to achieve. Additionally, the optimized structure of the minimized energy geometries and spatial distributions of carbazole derivatives was calculated using density functional theory (DFT), new materials can be developed and designed selectively based on the method proposed in this work.
Computational Study of the Substitution Effect on the Mechanism for the Gold(I)‐Catalyzed Ring Expansions of Unactivated Alkynylcyclopropanes
Authors: Kuo Tzu‐Nung , Liao Hsin‐Yi
Published: March 2013

The ring expansion reactions of unactivated alkynylcyclopropanes X‐C≡C‐C3H5 → X‐C=C4H5 (X = H, F, Cl, Me, OMe, NMe2, CMe3) were examined using the density functional theory calculations. All of the structures were completely optimized at the B3LYP/6‐311++G** level of theory. For clarify the effect of the cationic gold(I), we also added AuPH3+ as the catalyst into the system and the structures for Au were calculated at the B3LYP/LANL2DZ level of theory. The main finding of this work is that the singlet‐triplet splitting of X‐C≡C‐C3H5 play an important role in determining the kinetic and thermodynamic stability of the unactivated ring expansion reactions. When X‐C≡C‐C3H5 with a smaller singlet‐triplet splitting is utilized, the reaction has a smaller activation energy and a larger exothermicity.
Synthesis, Characterization and Oxide Ionic Conductivity of Binary δ‐(Bi2o3)1‐x(Lu2o3)x System
Authors: Öztürk Esra , Kalaycioglu Nilgun Ozpozan
Published: March 2013

In this study, after doping Lu2O3 to α‐Bi2O3 in the range of 11% ≤ n ≤ 20% in a series of different mole ratios, heat treatment was performed by applying a cascade temperature rise in the range of 700‐800 °C for 72 hours and new phases were obtained in the (Bi2o3)1‐x(Lu2o3)x system. After 72 hours of heat treatment at 800 °C, mixtures containing 14‐16% Lu2O3 formed a face‐centered cubic phase. Mixtures containing 11– 13%, 17%, 18% mole Lu2O3 were subjected to a quenching process at 825 °C and face‐centered cubic phases were obtained. With the help of XRD, the crystal systems and lattice parameters of the solid solutions were obtained and their characterization was carried out. Thermal measurements were made by using a simultaneous DTA/TG system. The total conductivity (σT) in the δ‐Bi2O3 doped with Lu2O3 system was measured using the four‐probe DC method. Keywords: Bismuth oxide; lutesium oxide; oxygen ionic conductivity; X‐ray techniques; thermal analysis.
Photolysis of Dibenzo[a,d]cycloheptene Dimer
Authors: Chang Meng‐Yang , Huang Yu‐Ping
Published: March 2013

Photolysis reaction of dibenzo[a,d]cycloheptene dimer 3 provides three dibenzo[a,d]cycloheptyl dimers 4, 5 and 6 under different irradiation conditions via the intramolecular degradative cyclodimerization. A tetracyclic benzo[4,5]cyclohepta[1,2,3‐de]naphthalene core is also synthesized.
Nonnative Pacific salmon alter hot spots of sediment nitrification in Great Lakes tributaries
Authors: Levi Peter S. , Tank Jennifer L.
Published: March 2013

Biogeochemical transformations may represent an important pathway influencing the fate of nutrient subsidies in stream ecosystems. Pacific salmon (Oncorhynchus spp.) provide an ammonium (NH4+) subsidy to streams during their annual spawning runs, which may be transformed to nitrate (NO3−) via sediment nitrification. Increases in either forms of dissolved inorganic nitrogen may have ecosystem effects both at the reach and watershed scales, including the fertilization of algal biofilms and elevated export of nutrients to downstream ecosystems. In the nonnative range of salmon, where spawning runs are a relatively new phenomenon, few studies have explored the effect of introduced salmon on ecosystem processes. To assess the effect of nonnative salmon on dissolved inorganic nitrogen dynamics in Great Lakes tributaries, we quantified sediment nitrification in five streams before, during, and after the spawning run in 2009. Overall, sediment nitrification rates were higher in the channel thalweg (mean ± SE = 1.9 ± 0.1 mg N/gAFDM/d) compared to channel margins (mean ± SE = 0.9 ± 0.1 mg N/gAFDM/d). In the two streams with the largest salmon runs, nitrification was highest in the channel thalweg prior to salmon, but margin sediments had higher nitrification during the run. Among all streams, variation in nitrification rates was habitat specific, predicted by exchangeable NH4+ in sediments from the thalweg and predicted by salmon biomass for sediments in the channel margin. Nonnative salmon provide a pulsed source of inorganic nitrogen to Great Lakes tributaries, yet dissimilatory biogeochemical transformations such as nitrification may alter the form of the NH4+ subsidy and potentially influence downstream lakes via export of both NH4+ and NO3−.
Mass‐biased partitioning to enhance middle down proteomics analysis
Authors: Cannon Joe R. , Edwards Nathan J. , Fenselau Catherine
Published: March 2013

A strategy is presented for enhancing the middle‐down analysis of higher mass peptides recovered from complex protein mixtures. Following a 30‐min digestion of multiple myeloma cell lysate by an acid cleavage reaction that is selective for aspartic acid, a 3000 Da membrane filter is used to bifurcate the peptide product mixture, and the heavier fraction is subjected to collisional activation with precursor selection that excludes charge states below +4. Filtration and charge state selection are shown to provide significant increases in the number of peptides identified in the mass range above 3000 Da and in information about protein sequences. Copyright © 2013 John Wiley & Sons, Ltd.
EGb761 inhibits inflammatory responses in human chondrocytes and shows chondroprotection in osteoarthritic rat knee
Authors: Chen Ying Ju , Tsai Keh Sung , Chiu Chen Yuan , Yang Ting Hua , Lin Tzu Hung , Fu Wen Mei , Chen Cheng Feng , Yang Rong Sen , Liu Shing Hwa
Published: March 2013

Osteoarthritis (OA) is a degenerative joint disease involving a combination of cartilage degradation and inflammation. EGb761, a standardized extract of Ginkgo biloba leaves, holds an anti‐inflammatory potency. Here, we determined whether EGb761 could inhibit lipopolysaccharide (LPS)‐ and IL‐1β‐induced inflammatory responses in human articular chondrocytes and apply the chondroprotection in OA rats. We found that LPS markedly induced the productions of PGE2 and NO and the protein expressions of COX‐2 and iNOS in human chondrocytes. LPS was also seen to up‐regulate the expressions of toll‐like receptor‐4 (TLR4), its downstream signal TNF receptor‐associated factor 6 (TRAF6), and nuclear factor (NF)‐κB signaling. These LPS‐induced inflammatory responses were efficaciously reversed by EGb761 and its active components quercetin and kampferol. The similar results could be observed by using IL‐1β as an in vitro model to mimic an inflammatory response. In an OA rat model, PGE2 and NO levels in blood, the histological alterations, and COX‐2 and nitrotyrosine expressions in cartilages were markedly increased, which were effectively reversed by EGb761. Our results suggested that EGb761 exerts the anti‐inflammatory effects on human articular chondrocytes and OA rats. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1032–1038, 2013
Autostereoscopic 3D pictures on optically rewritable electronic paper
Authors: Wang Xiaoqian , Wang Lu , Sun Jiatong , Srivastava Abhishek K. , Chigrinov Vladimir G. , Kwok Hoi Sing
Published: March 2013

In this article, we disclose a method to fabricate the three‐dimensional (3D) image on an optically rewritable (ORW) electronic paper (e‐paper) by deploying the lenticular lenses array on the top of the ORW e‐paper. Unlike other autostereoscopic 3D liquid crystal displays, our autostereoscopic 3D ORW e‐paper is actually a green technology, which is without electrode and voltage. No electricity is needed to maintain the 3D image on the ORW e‐paper. We can easily change a 3D image by erasing and rewriting with photoalignment technology.
Salvage Circular Laryngopharyngectomy and Radial Forearm Free Flap for Recurrent Hypopharyngeal Cancer
Authors: Fakhry Nicolas , Chamorey Emmanuel , Michel Justin , Collet Charles , Santini Laure , Poissonnet Gilles , Santini José , Dessi Patrick , Giovanni Antoine , Dassonville Olivier , Bozec Alexandre
Published: March 2013

Objectives/Hypothesis:

To evaluate surgical and long‐term oncologic outcomes in a series of patients who underwent circular total laryngopharyngectomy with tubed radial forearm free flap as salvage surgery.

Study Design:

Retrospective study in two tertiary referral centers.

Methods:

Twenty‐one patients who underwent surgery between 2001 and 2010 were included in the study. All patients underwent surgery for recurrence of advanced hypopharyngeal squamous cell carcinoma previously treated by chemoradiotherapy (CRT) or surgery followed by postoperative radiotherapy or CRT. Overall survival (OS) and disease‐free survival (DFS) were determined by Kaplan‐Meier analysis. The search for parameters that could influence long‐term oncologic outcomes was carried out by univariate and multivariate analysis using log‐rank test and Cox regression models.

Results:

Median follow‐up was 30 months. The 1, 2, and 5‐year OS rates were 46%, 40%, and 16%, and the DFS rates were 42%, 30%, and 15%, respectively. Free flap failure (P [log rank] = .014 and P [Cox] = .016) and positive margins (P [log rank] = .001 and P [Cox] = .001) were found to have a significant negative impact on both OS and DFS in both univariate and multivariate analysis.

Conclusions:

Salvage surgery remains the only curative option as treatment of recurrent hypopharyngeal squamous cell carcinoma and should be offered to patients when possible. However, selection of patients eligible for this type of surgery and the choice of reconstructive procedure are crucial since long‐term survival is clearly correlated with the presence of clear margins and the absence of free flap failure.
Smoking and malignancy in sinonasal inverted papilloma
Authors: Hong Sung‐Lyong , Kim Bae‐Hyun , Lee Jung‐Hoon , Cho Kyu‐Sup , Roh Hwan‐Jung
Published: March 2013

Objectives/Hypothesis

The authors investigated clinical features of squamous cell carcinomas (SCC) arising in sinonasal inverted papillomas (IP) and risk factors responsible for their malignant transformation.

Study Design

Retrospective analysis.

Methods

In total, 162 patients diagnosed with sinonasal IP and treated between 1998 and 2009 at Pusan National University Hospital were enrolled. Their demographic data, information about previous surgery, smoking history, treatment modalities, follow‐up duration, recurrence, and presence of malignancy were reviewed retrospectively.

Results

Seventeen patients (10.5%) were diagnosed with SCC arising in sinonasal IPs. Among them, nine (9/162, 5.6%; 9/17, 52.9%) were diagnosed with synchronous malignancies and three (3/162, 1.8%; 3/17, 17.6%) were diagnosed with metachronous malignancies. In five cases (5/162, 3.1%; 5/17, 29.4%), we could not determine whether their malignancies were synchronous or metachronous. Among 53 smokers, 14 (26.4%) had malignant transformation, while only three (2.8%) in 109 nonsmokers had malignant transformation (Odds ratio = 12.7; P < .001). The mean follow‐up in the 17 patients with malignancy was 47.0 months. Three patients did not receive surgical treatment and died of progression of SCC. Among the other 14 patients who underwent curative surgeries, four (28.6%) had recurrences, and their mean period to cancer recurrence was 6.3 months. Two of them died of progression of the cancer. Mean survival of the five patients who died was 14.0 months. They all belonged to T4 stage.

Conclusions

Smoking history is associated with malignant transformation of sinonasal IP. It suggests that close follow‐up be required in smokers with sinonasal IP in order not to overlook the malignant transformation.

Level of Evidence

2b.