bluuebunny/crossref_metadata_2025 huggingface dataset:
C3‐Symmetric Cinchonine‐Squaramide‐Catalyzed Asymmetric Chlorolactonization of Styrene‐Type Carboxylic Acids with 1,3‐Dichloro‐5,5‐dimethylhydantoin: An Efficient Method to Chiral Isochroman‐1‐ones
Authors: Han Xin , Dong Chune , Zhou Hai‐Bing
Published: March 2014

A more practical and efficient catalytic asymmetric chlorolactonization of styrene‐type carboxylic acids with 1,3‐dichloro‐5,5‐dimethylhydantoin (DCDMH) using C3‐symmetric cinchonine‐squaramide (CSCS) as organocatalyst has been developed. A series of chiral chloro‐substituted isochroman‐1‐ones was obtained in excellent yields (up to 95%) and enantioselectivities (up to 99% ee), whwereby the results for chloro‐substituted isochroman‐1‐ones are the best ever achieved. The catalyst can be recovered and reused for six cycles. Moreover, the chlorolactonization product 3b was further transformed to optically active bicyclic isochroman‐1‐one derivatives in high yield without losing the enantioselectivity. Furthermore, compounds 3e and 2n proved to be highly potent inhibitors of the HIV‐1 in TZM‐bl cells.

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Lösungsmittelunterstützter Linker‐Austausch: eine Alternative zur De‐novo‐Synthese von Metall‐organischen Gerüsten
Authors: Karagiaridi Olga , Bury Wojciech , Mondloch Joseph E. , Hupp Joseph T. , Farha Omar K.
Published: March 2014

Metall‐organische Gerüste (MOFs) sind Hybridmaterialien, die anhaltendes Interesse auf sich ziehen – nicht zuletzt wegen vielfältiger möglicher Anwendungen, von der Gastrennung über die Katalyse bis hin zum Sammeln von Licht. Allerdings ist die De‐novo‐Synthese von MOFs mit gewünschten Eigenschaften nicht immer einfach: unerwünschte Topologien können entstehen, die Löslichkeit von Vorstufen kann zu gering sein, und die Funktionalität wichtiger Netzwerkkomponenten kann verlorengehen. Mit einem neuen Ansatz – dem lösungsmittelunterstützten Linker‐Austausch (“solvent‐assisted linker exchange”, SALE) – lassen sich diese Probleme umgehen, und tatsächlich wurden mit SALE bereits verschiedene MOF‐Materialien erzeugt, die durch direkte Syntheseverfahren nicht erhältlich waren. Unsere Übersicht beschreibt Forschungsergebnisse über MOFs, die erst durch SALE möglich gemacht wurden, und diskutiert Studien, die das Verständnis dieses Verfahrens verbessert und sein Anwendungsgebiet erweitert haben.
An Electroactive Biotin‐Doped Polypyrrole Substrate That Immobilizes and Releases EpCAM‐Positive Cancer Cells
Authors: Jeon SeungHyun , Moon Jeong‐Mi , Lee Eun Sook , Kim Yon Hui , Cho Youngnam
Published: March 2014

The specific capture and remotely controlled release of the EpCAM‐positive cancer cells from biotin‐doped polypyrrole (Ppy) films in response to an electrical potential is presented. As Ppy allows the direct incorporation of biotin molecules during the electrochemical process, densely packed biotin molecules can serve as the binding sites for streptavidin‐tagged biomolecular complexes. This study demonstrates not only the enhanced capture and enrichment of EpCAM‐positive cancer cells but also “on‐demand” release of the viable cells from conductive Ppy in an electrical‐potential‐dependent way. This novel approach is of great importance in a diverse range of applications, and in particular in cancer diagnostics and screening.
Discovery of a Novel Series of Tetrahydro‐β‐carbolines Inducing Autophagic Cell Death in Human Metastatic Melanoma
Authors: Ahmed Nermin S. , Elgendy Mohamed , Laufer Stefan , Abadi Ashraf H.
Published: March 2014

Herein, we report the synthesis of novel tetrahydro‐β‐carbolines that induce cell death via the autophagic pathway. Five of the new compounds induced cell death in a panel of patient‐derived human metastatic melanoma cells. The autophagic pathway was confirmed using LC3 autophagosome markers; the involvement of ATG7 and Beclin 1 autophagy regulating genes was confirmed using infection with short hairpin RNA (shRNA) to silence Beclin 1 and ATG7. Compound VIII (IC50 = 2.34–5.15 μM) displayed activities greater than cisplatin against a panel of patient‐derived human metastatic melanoma cell lines. The structure–activity relationship (SAR) of this class and the role of the absolute stereochemistry and geometrical isomerism are evaluated.
Robot-assisted pancreatic surgery
Authors: Coratti A , Annecchiarico M
Published: March 2014

Advantages for robotic-assistance in complex resectional surgery
Systematic review of surgical management of synchronous colorectal liver metastases
Authors: Lykoudis P M , O'Reilly D , Nastos K , Fusai G
Published: March 2014

Background

The optimal management of colorectal cancer with synchronous liver metastases has not yet been elucidated. The aim of the present study was systematically to review current evidence concerning the timing and sequence of surgical interventions: colon first, liver first or simultaneous.

Methods

A systematic literature review was performed of clinical studies comparing the timing and sequence of surgical interventions in patients with synchronous liver metastases. Retrospective studies were included but case reports and small case series were excluded. Preoperative and intraoperative data, length of hospital stay, perioperative mortality and morbidity, and 1-, 3- and 5-year survival rates were compared. The studies were evaluated according to a modification of the methodological index for non-randomized studies (MINORS) criteria.

Results

Eighteen papers were included and 21 entries analysed. Five entries favoured the simultaneous approach regarding duration of procedure, whereas three showed no difference; five entries favoured simultaneous treatment in terms of blood loss, whereas in four there was no difference; and all studies comparing length of hospital stay favoured the simultaneous approach. Five studies favoured the simultaneous approach in terms of morbidity and eight found no difference, and no study demonstrated a difference in perioperative mortality. One study suggested a better 5-year survival rate after staged procedures, and another suggested worse 1-year but better 3- and 5-year survival rates following the simultaneous approach. The median MINORS score was 10, with incomplete follow-up and outcome reporting accounting primarily for low scores.

Conclusion

None of the three surgical strategies for synchronous colorectal liver metastases appeared inferior to the others.
Teaching foundational topics and scientific skills in biochemistry within the conceptual framework of HIV protease
Authors: Johnson R. Jeremy
Published: March 2014

HIV protease has served as a model protein for understanding protein structure, enzyme kinetics, structure‐based drug design, and protein evolution. Inhibitors of HIV protease are also an essential part of effective HIV/AIDS treatment and have provided great societal benefits. The broad applications for HIV protease and its inhibitors make it a perfect framework for integrating foundational topics in biochemistry around a big picture scientific and societal issue. Herein, I describe a series of classroom exercises that integrate foundational topics in biochemistry around the structure, biology, and therapeutic inhibition of HIV protease. These exercises center on foundational topics in biochemistry including thermodynamics, acid/base properties, protein structure, ligand binding, and enzymatic catalysis. The exercises also incorporate regular student practice of scientific skills including analysis of primary literature, evaluation of scientific data, and presentation of technical scientific arguments. Through the exercises, students also gain experience accessing computational biochemical resources such as the protein data bank, Proteopedia, and protein visualization software. As these HIV centered exercises cover foundational topics common to all first semester biochemistry courses, these exercises should appeal to a broad audience of undergraduate students and should be readily integrated into a variety of teaching styles and classroom sizes. © 2014 by The International Union of Biochemistry and Molecular Biology, 42(4):299–304, 2014.
Thickening of the knee joint cartilage in elite weightlifters as a potential adaptation mechanism
Authors: Grzelak Piotr , Domzalski Marcin , Majos Agata , Podgórski Michal , Stefanczyk Ludomir , Krochmalski Marek , Polguj Michal
Published: March 2014

Thickening and increase of area of cartilage have been proposed as two alternative mechanisms of cartilage functional adaptation. The latter has been reported in endurance sportsmen. In weightlifters, extreme strain applied to the articular surfaces can result in other forms of adaptation. The aim of this research is to determine whether cartilage thickness is greater in elite weightlifters than in physically inactive men. Weightlifters (13) and 20 controls [age and body mass index (BMI) matched] underwent knee Magnetic Resonance Imaging (MRI). A single sagittal slice of the knee was taken and cartilage thickness was measured in five and six regions of the medial and lateral femoral condyles, respectively. The analyzed segments represented weight‐bearing and nonweight‐bearing regions. The tibia cartilage in the weight‐bearing area was also measured. The time of training onset and its duration in the weightlifter group were recorded. The cartilage was found to be significantly thicker in weightlifters in most of the analyzed regions. The distribution of cartilage thickness on the medial and lateral femoral condyles was similar in both groups. The duration of training was not associated with cartilage thickness, but the time of training onset correlated inversely with cartilage thickness. It is possible that in high‐strain sports, joint cartilage can undergo functional adaptation by thickening. Thus, mechanical loading history could exert a postnatal influence on cartilage morphology. Clin. Anat. 27:920–928, 2014. © 2014 Wiley Periodicals, Inc.
Terpendole E and its Derivative Inhibit STLC‐ and GSK‐1‐Resistant Eg5
Authors: Tarui Yuka , Chinen Takumi , Nagumo Yoko , Motoyama Takayuki , Hayashi Toshiaki , Hirota Hiroshi , Muroi Makoto , Ishii Yasuyuki , Kondo Hisae , Osada Hiroyuki , Usui Takeo
Published: March 2014

Terpendole E is first natural product found to inhibit mitotic kinesin Eg5, but its inhibitory mechanism remains to be revealed. Here, we report the effects of terpendole E and 11ketopaspaline (a new natural terpendole E analogue) on the Eg5–microtubule interaction and in several Eg5 mutants. 11‐Ketopaspaline is a shunt product from terpendole E, and it shows potent inhibitory activity against the microtubule‐stimulated ATPase activity of Eg5. Unlike other Eg5 inhibitors, such as S‐trityl‐L‐cysteine (STLC) and GSK‐1, both terpendole E and 11‐ketopaspaline only partially inhibited Eg5–microtubule interaction. Furthermore, terpendole E and 11‐ketopaspaline inhibited several Eg5 mutants that are resistant to STLC (Eg5D130A, Eg5L214A) or GSK‐1 (Eg5I299F, Eg5A356T), but with the same extent of inhibition against wild‐type Eg5. Because Eg5D130A and Eg5L214A show cross‐resistance to most known Eg5 inhibitors, which bind the L5 loop, these results suggest that terpendole E and its analogues have a different binding site and/or inhibitory mechanism to those for L5 loop‐binding type Eg5 inhibitors.
Helical Carbon Segment in Carbon–Boron–Nitride Heteronanotubes: Structure and Nonlinear Optical Properties
Authors: Zhong Rong‐Lin , Sun Shi‐Ling , Xu Hong‐Liang , Qiu Yong‐Qing , Su Zhong‐Min
Published: March 2014

Carbon–boron–nitride heteronanotubes have attracted much interest owing to their adjustable properties and wide applications in many fields. In this work, the structures and first hyperpolarizabilities (β0) of a series of HA‐n and isoelectronic PA‐n heteronanotubes are investigated, in which HA‐n is composed of a helical C segment and BN segment, and PA‐n is composed of an arc C segment and BN segment. Interestingly, the helix C segment in HA‐9 leads to a fascinating long‐range charge‐transfer character. As a result, the β0 value of HA‐9 is 1.80×104 a.u., which is much larger than that of PA‐9 (4.99×103 a.u.). Significantly, the β0 value of the C segment in HA‐9 is 1.72×104 a.u., whereas that of the BN segment in HA‐9 is much smaller (7.48×102 a.u.). In this context, the larger β0 value of HA‐9 is essentially induced by the helix topological effect of the C segment. It is our expectation that this new knowledge about heteronanotubes might provide more ideas for further exploration of sp2‐hybridized carbon segments with special topologies.
Cannabinoid disposition in oral fluid after controlled cannabis smoking in frequent and occasional smokers
Authors: Newmeyer Matthew N. , Desrosiers Nathalie A. , Lee Dayong , Mendu Damodara R. , Barnes Allan J. , Gorelick David A. , Huestis Marilyn A.
Published: March 2014

Oral fluid (OF) is an increasingly popular alternative matrix for drug testing, with cannabinoids being the most commonly identified illicit drug. Quantification of multiple OF cannabinoids and understanding differences in OF cannabinoid pharmacokinetics between frequent and occasional smokers improve test interpretation. The new Oral‐Eze® OF collection device has an elution buffer that stabilizes analytes and improves drug recovery from the collection pad; however, its performance has not been independently evaluated. After controlled smoking of a 6.8% Δ9‐tetrahydrocannabinol (THC) cannabis cigarette by frequent and occasional smokers, OF was collected with the Oral‐Eze device for up to 30 h. Samples were analyzed for multiple cannabinoids by a validated 2D‐GC‐MS method. Frequent smokers had significantly greater OF THCCOOH concentrations than occasional smokers at all times, and showed positive results for a significantly longer time. We evaluated multiple cannabinoid cut‐offs; the shortest last detection times were observed when THC ≥1μg/L was combined with CBD or CBN ≥1μg/L. With these cut‐offs, last detection times(1‐13.5 h) were not significantly different between groups, demonstrating suitability for short‐term cannabinoid detection independent of smoking history. Cut‐offs utilizing THC alone or combined with THCCOOH showed significantly different last detection times between groups. The widest detection windows were observed with THC ≥1 or 2μg/L or THCCOOH ≥20ng/L. Our data illustrate the effectiveness of the Oral‐Eze® device for OF collection, the impact of self‐administered smoked cannabis history on OF cannabinoid results, and the ability to improve interpretation and tailor OF cannabinoid cut‐offs to fulfill the detection window needs of a given program. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Early left‐right asymmetries during axial morphogenesis in the chick embryo
Authors: Otto Annalena , Pieper Tobias , Viebahn Christoph , Tsikolia Nikoloz
Published: March 2014

The primitive node is the “hub” of early left‐right patterning in the chick embryo: (1) it undergoes asymmetrical morphogenesis immediately after its appearance at Stage 4; (2) it is closely linked to the emerging asymmetrical expression of nodal and shh at Stage 5; and (3) its asymmetry is spatiotemporally related to the emerging notochord, the midline barrier maintaining molecular left‐right patterning from Stage 6 onward. Here, we study the correlation of node asymmetry to notochord marker expression using high‐resolution histology, and we test pharmacological inhibition of shh signaling using cyclopamine at Stages 4 and 5. Just as noggin expression mirrors an intriguing structural continuity between the right node shoulder and the notochord, shh expression in the left node shoulder confirms a similar continuity with the future floor plate. Shh inhibition at Stage 4 or 5 suppressed nodal in both its paraxial or lateral plate mesoderm domains, respectively, and resulted in randomized heart looping. Thus, the “primordial” paraxial nodal asymmetry at Stage 4/5 (1) appears to be dependent on, but not instructed by, shh signaling and (2) may be fixed by asymmetrical roots of the notochord and the floor plate, thereby adding further twists to the node's pivotal role during left‐right patterning. genesis 52:614–625, 2014. © 2014 Wiley Periodicals, Inc.
110 Years of change in urban tree stocks and associated carbon storage
Authors: Díaz‐Porras Daniel F. , Gaston Kevin J. , Evans Karl L.
Published: March 2014

Understanding the long‐term dynamics of urban vegetation is essential in determining trends in the provision of key resources for biodiversity and ecosystem services and improving their management. Such studies are, however, extremely scarce due to the lack of suitable historical data. We use repeat historical photographs from the 1900s, 1950s, and 2010 to assess general trends in the quantity and size distributions of the tree stock in urban Sheffield and resultant aboveground carbon storage. Total tree numbers declined by a third from the 1900s to the 1950s, but increased by approximately 50% from the 1900s–2010, and by 100% from the 1950s–2010. Aboveground carbon storage in urban tree stocks had doubled by 2010 from the levels present in the 1900s and 1950s. The initial decrease occurred at a time when national and regional tree stocks were static and are likely to be driven by rebuilding following bombing of the urban area during the Second World War and by urban expansion. In 2010, trees greater than 10 m in height comprised just 8% of those present. The increases in total tree numbers are thus largely driven by smaller trees and are likely to be associated with urban tree planting programmes. Changes in tree stocks were not constant across the urban area but varied with the current intensity of urbanization. Increases from 1900 to 2010 in total tree stocks, and smaller sized trees, tended to be greatest in the most intensely urbanized areas. In contrast, the increases in the largest trees were more marked in areas with the most green space. These findings emphasize the importance of preserving larger fragments of urban green space to protect the oldest and largest trees that contribute disproportionately to carbon storage and other ecosystem services. Maintaining positive trends in urban tree stocks and associated ecosystem service provision will require continued investment in urban tree planting programmes in combination with additional measures, such as revisions to tree preservation orders, to increase the retention of such trees as they mature.
Use of posterior predictive checks as an inferential tool for investigating individual heterogeneity in animal population vital rates
Authors: Chambert Thierry , Rotella Jay J. , Higgs Megan D.
Published: March 2014

The investigation of individual heterogeneity in vital rates has recently received growing attention among population ecologists. Individual heterogeneity in wild animal populations has been accounted for and quantified by including individually varying effects in models for mark–recapture data, but the real need for underlying individual effects to account for observed levels of individual variation has recently been questioned by the work of Tuljapurkar et al. (Ecology Letters, 12, 93, 2009) on dynamic heterogeneity. Model‐selection approaches based on information criteria or Bayes factors have been used to address this question. Here, we suggest that, in addition to model‐selection, model‐checking methods can provide additional important insights to tackle this issue, as they allow one to evaluate a model's misfit in terms of ecologically meaningful measures. Specifically, we propose the use of posterior predictive checks to explicitly assess discrepancies between a model and the data, and we explain how to incorporate model checking into the inferential process used to assess the practical implications of ignoring individual heterogeneity. Posterior predictive checking is a straightforward and flexible approach for performing model checks in a Bayesian framework that is based on comparisons of observed data to model‐generated replications of the data, where parameter uncertainty is incorporated through use of the posterior distribution. If discrepancy measures are chosen carefully and are relevant to the scientific context, posterior predictive checks can provide important information allowing for more efficient model refinement. We illustrate this approach using analyses of vital rates with long‐term mark–recapture data for Weddell seals and emphasize its utility for identifying shortfalls or successes of a model at representing a biological process or pattern of interest.
Crystal and Electronic Structures and Magnetic Properties of Eu3Tt2As4 (Tt = Si, Ge)
Authors: Liu Xiao‐Cun , Xia Sheng‐Qing , Lei Xiao‐Wu , Pan Ming‐Yan , Tao Xu‐Tang
Published: March 2014

Two new europium‐containing Zintl phases, Eu3Si2As4 and Eu3Ge2As4, were discovered from metal flux reactions and their structures were identified by using single‐crystal X‐ray diffraction. Both compounds crystallize in the monoclinic space group P21/c and are isotypic to Sr3Ge2As4. Magnetic property studies were performed and the results proved the long‐range antiferromagnetic behavior for Eu3Ge2As4 but with a positive Weiss constant, which suggested the coexistence of both ferromagnetic and antiferromagnetic order of Eu 4f electrons in the structure. Density functional calculations were incorporated to understand the related magnetic properties as well.
Changes in matrix metalloprotease activity and progranulin levels may contribute to the pathophysiological function of mutant leucine‐rich repeat kinase 2
Authors: Caesar Mareike , Felk Sandra , Zach Susanne , Brønstad Gunnar , Aasly Jan O. , Gasser Thomas , Gillardon Frank
Published: March 2014

Increasing evidence suggests that Parkinson's disease (PD)‐linked Leucine‐rich repeat kinase 2 (LRRK2) has a role in peripheral and brain‐resident immune cells. Furthermore, dysregulation of the anti‐inflammatory, neurotrophic protein progranulin (PGRN) has been demonstrated in several chronic neurodegenerative diseases. Here we show that PGRN levels are significantly reduced in conditioned medium of LRRK2(R1441G) mutant mouse fibroblasts, leukocytes, and microglia, whereas levels of proinflammatory factors, like interleukin‐1β and keratinocyte‐derived chemokine, were significantly increased. Decreased PGRN levels were also detected in supernatants of cultured human fibroblasts isolated from presymptomatic LRRK2(G2019S) mutation carriers, while mitochondrial function was unaffected. Furthermore, medium levels of matrix metalloprotease (MMP) 2 increased, whereas MMP 9 decreased in LRRK2(R1441G) mutant microglia. Increased proteolytic cleavage of the MMP substrates ICAM‐5 and α‐synuclein in synaptoneurosomes from LRRK2(R1441G) mutant mouse brain indicates increased net synaptic MMP activity. PGRN levels were decreased in the cerebrospinal fluid of presymptomatic LRRK2 mutant mice, whereas PGRN levels were increased in aged symptomatic mutant mice. Notably, PGRN levels were also increased in the cerebrospinal fluid of PD patients carrying LRRK2 mutations, but not in idiopathic PD patients and in healthy control donors. Our data suggest that proinflammatory activity of peripheral and brain‐resident immune cells may particularly contribute to the early stages of Parkinson's disease caused by LRRK2 mutations. GLIA 2014;62:1075–1092
Involvement of immune‐ and inflammatory‐related factors in flucloxacillin‐induced liver injury in mice
Authors: Takai Shohei , Higuchi Satonori , Yano Azusa , Tsuneyama Koichi , Fukami Tatsuki , Nakajima Miki , Yokoi Tsuyoshi
Published: March 2014

Drug‐induced liver injury (DILI) is a serious problem in pre‐clinical stages of drug development and clinical pharmacotherapy, but the pathogenesis of DILI has not been elucidated. Flucloxacillin (FLX), which is a β‐lactam antibiotic of the penicillin class that is used widely in Europe and Australia, rarely causes DILI. Clinical features suggest that FLX‐induced liver injury is caused by immune‐ and inflammatory‐related factors, but the mechanism of FLX‐induced liver injury is unknown. The purpose of this study was to elucidate the mechanisms of FLX‐induced liver injury in vivo. Plasma alanine aminotransferase, aspartate aminotransferase and total‐bilirubin levels were significantly elevated in FLX‐administered mice [1000 mg kg–1, intraperitoneally (i.p.)]. Toll‐like receptor 4 (TLR4) ligands, such as high‐mobility group box 1 (HMGB1) and S100A8/A9, were significantly increased in FLX‐administered mice, and inflammatory factors, such as interleukin (IL)‐1β, tumor necrosis factor‐alpha (TNF‐α), macrophage inflammatory protein (MIP)‐2, CXC chemokine‐ligand‐1 (CXCL1) and monocyte chemoattractant protein (MCP)‐1, were also significantly elevated. IL‐17‐related transcriptional factors and cytokines were increased, and the administration of recombinant IL‐17 (2 mg per body weight, i.p.) resulted in an exacerbation of the FLX‐induced liver injury. TLR4‐associated‐signal transduction may be involved in FLX‐induced liver injury, and IL‐17 is an exacerbating factor. Copyright © 2014 John Wiley & Sons, Ltd.
A balanced procedure for the treatment of cluster–ligand interactions on gold phosphine systems in catalysis
Authors: Mollenhauer Doreen , Gaston Nicola
Published: March 2014

Ligand‐protected metal clusters are difficult to describe within density functional theory due to the need to treat the electronic structure of the cluster, possible charge transfer between the ligands and the cluster, and weak ligand–ligand interactions in a balanced manner. We demonstrate the use of an appropriate, stepwise benchmarking process that accounts for the nonadditivity of these different contributions to stability and catalytic activity. We consider both open‐ and closed‐shell clusters, differently charged systems, and ligands of increasing complexity for gold phosphine systems. The use of a dispersion correction to density functional calculations was found to be crucial for both structure optimization and the calculation of binding energies. We find that PBE‐D3 performs well with a variation in energetics of 0.7–10.9 kcal/mol, PBE0‐D3 better with 0.0–3.3 kcal/mol, and B2PLYP‐D3 the best with 0.2–2.4 kcal/mol, when compared to the best available benchmark [CCSD(T) or SCS‐MP2]. Our systematic procedure clarifies that these functionals all give accurate results for certain cases, but for the total performance over a range of interactions, they perform in accordance with Jacob's ladder. © 2014 Wiley Periodicals, Inc.
Disadvantages of interfragmentary shear on fracture healing—mechanical insights through numerical simulation
Authors: Steiner Malte , Claes Lutz , Ignatius Anita , Simon Ulrich , Wehner Tim
Published: March 2014

The outcome of secondary fracture healing processes is strongly influenced by interfragmentary motion. Shear movement is assumed to be more disadvantageous than axial movement, however, experimental results are contradictory. Numerical fracture healing models allow simulation of the fracture healing process with variation of single input parameters and under comparable, normalized mechanical conditions. Thus, a comparison of the influence of different loading directions on the healing process is possible. In this study we simulated fracture healing under several axial compressive, and translational and torsional shear movement scenarios, and compared their respective healing times. Therefore, we used a calibrated numerical model for fracture healing in sheep. Numerous variations of movement amplitudes and musculoskeletal loads were simulated for the three loading directions. Our results show that isolated axial compression was more beneficial for the fracture healing success than both isolated shearing conditions for load and displacement magnitudes which were identical as well as physiological different, and even for strain‐based normalized comparable conditions. Additionally, torsional shear movements had less impeding effects than translational shear movements. Therefore, our findings suggest that osteosynthesis implants can be optimized, in particular, to limit translational interfragmentary shear under musculoskeletal loading. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:865–872, 2014.
Enhancement in SERS intensities of azo dyes adsorbed on ZnO by plasma treatment
Authors: Liu Chih‐Sheng , Li Bing‐Han , Chen Chih‐Hsuan , Peng Jr‐Wei , Lee Szetsen
Published: March 2014

Surface‐enhanced Raman scattering (SERS) spectra of azo dyes (methyl orange and p‐methyl red) adsorbed on ZnO nanoparticles were observed. Hydrothermally synthesized ZnO nanoparticles were characterized by powder X‐ray diffraction and X‐ray photoelectron spectroscopy. The ZnO nanoparticle size, monitored with X‐ray diffraction, was tuned by calcination to optimize SERS intensities. The observed SERS effect of azo dyes adsorbed on ZnO can be ascribed to charge‐transfer resonance effect. Time‐dependent density functional theory was used to calculate the optical spectra and interpret the chemical enhancement observed in the experiment. The SERS enhancement factors for methyl red on ZnO were boosted by nearly four times and twice with O2 plasma and H2 plasma, respectively. However, plasma treatment showed no effect on the enhancement factors of methyl orange on ZnO. We conclude that plasma‐induced defect formation and band gap shift in ZnO and the coupling of energy levels between ZnO and azo dye molecules are responsible for the observed enhancement of SERS intensities. Copyright © 2014 John Wiley & Sons, Ltd.
Reduction of aflatoxin B1 to aflatoxicol: A comprehensive DFT study provides clues to its toxicity
Authors: Karabulut Sedat , Paytakov Guvanchmyrat , Leszczynski Jerzy
Published: March 2014

BACKGROUND

Aflatoxicol (AFL) is one of most the important metabolites of aflatoxin B1 (AFB1). AFL can be formed through enzymatic or synthetic reduction of AFB1. Various experimental and theoretical studies have been focused on the AFB1 due to its high toxicity and carcinogenicity.

RESULTS

The selective reduction of AFB1 carbonyls, molecular structure of AFL and its effect on toxicity has been studied here by the density functional theory (DFT) method. Although the toxicity of AFL is 18 times lower than that of AFB1, it has been concluded that both molecular structures have similar potency to form an exo‐epoxide (AFEP) analogue which can bind to DNA.

CONCLUSION

Calculations revealed that only one of the three possible tautomers of AFL is stable, both in the gas phase and water. The electronic properties of aflatoxicol are calculated as similar to aflatoxin B1 and this may be an explanation of similar carcinogenicity and toxicity of these compounds, which has been proved by experimental results. © 2014 Society of Chemical Industry
Microwave‐assisted extraction coupled with countercurrent chromatography for the rapid preparation of flavonoids from Scutellaria barbata D. Don
Authors: Ruan Chong , Xiao Xiao‐hua , Li Gong‐ke
Published: March 2014

As a famous Chinese herb having good inhibitory effects on numerous human cancers both in vitro and in vivo, Scutellaria barbata D. Don attracts extensive attention worldwide. In this work, four flavonoids named scutellarin, baicalin, luteolin, and apigenin were simply and rapidly prepared from S. barbata by microwave‐assisted extraction coupled to countercurrent chromatography. Extraction conditions including irradiation time, extraction temperature, liquid/solid ratio, and microwave power were optimized using an orthogonal array design method. The extract of S. barbata was separated and purified with a two‐phase solvent system composed of hexane/ethyl acetate/methanol/acetic acid/water (1:5:1.5:1:4, v/v/v/v/v) and 4.5 mg of scutellarin, 4.6 mg of baicalin, 1.1 mg of luteolin, 2.1 mg of apigenin were obtained from 2.0 g original sample in a single run. The purities of scutellarin, baicalin, luteolin, and apigenin determined by HPLC were 93.6, 97.3, 97.6, and 98.4%, respectively. The targeted compounds were identified by LC with MS and 1H NMR spectroscopy. The total time including extraction, separation, and purification was <300 min. Compared to traditional methods, microwave‐assisted extraction coupled to countercurrent chromatography method is more simple and rapid for the extraction, separation, and purification of flavonoid compounds from natural products.
Otoscopy simulation training in a classroom setting: A novel approach to teaching otoscopy to medical students
Authors: Davies Joel , Djelic Lucas , Campisi Paolo , Forte Vito , Chiodo Albino
Published: March 2014

Objectives/Hypothesis

To determine the effectiveness of using of an otoscopy stimulator to teach medical students the primary principles of otoscopy in large group training sessions and improve their confidence in making otologic diagnoses.

Study Design

Cross‐sectional survey design.

Methods

In March 2013, the Department of Otolaryngology–Head and Neck Surgery held a large‐scale otoscopy simulator teaching session at the MaRS Innovation Center for 92 first and second year University of Toronto medical students. Following the training session, students were provided with an optional electronic, nine‐question survey related to their experience with learning otoscopy using the simulators alone, and in comparison to traditional methods of teaching.

Results

Thirty‐four medical students completed the survey. Ninety‐one percent of the respondents indicated that the overall quality of the event was either very good or excellent. A total of 71% of respondents either agreed, or strongly agreed, that the otoscopy simulator training session improved their confidence in diagnosing pathologies of the ear. The majority (70%) of students indicated that the training session had stimulated their interest in otolaryngology–head and neck surgery as a medical specialty.

Conclusions

Organizing large‐group otoscopy simulator training sessions is one method whereby students can become familiar with a wide variety of pathologies of the ear and improve both their diagnostic accuracy and their confidence in making otologic diagnoses.

Level of Evidence

NA Laryngoscope, 124:2594–2597, 2014
Long-term follow-up of portopulmonary hypertension patients after liver transplantation
Authors: Khaderi Saira , Khan Rashid , Safdar Zeenath , Stribling Rise , Vierling John M. , Goss John A. , Sussman Norman L.
Published: March 2014

Portopulmonary hypertension (POPH) occurs in 5.3% to 8.5% of patients with advanced liver disease. The rate of survival in the absence of orthotopic liver transplantation (OLT) is reportedly 38% at 3 years and 28% at 5 years. Moderate to severe POPH [mean pulmonary artery pressure (MPAP) ≥ 35 mm Hg] is associated with a perioperative mortality rate of 50%. Single-center series have demonstrated the feasibility and short-term efficacy of OLT after POPH is controlled with vasodilators, but long-term outcomes have not been reported. Our aim was to determine graft and patient survival rates and the effects of OLT on pulmonary hypertension (PHT) in patients undergoing transplantation for POPH at our center. Four hundred eighty-eight adult patients underwent transplantation between June 2004 and January 2011, and 7 underwent transplantation for POPH after their MPAP was reduced to ≤35 mm Hg with vasodilators. These 7 patients included 3 men and 4 women with ages ranging from 39 to 54 years at the time of OLT. All patients received IV EPO or inhaled EPO during the perioperative period, and all were weaned off EPO over the course of 3 days to 8 months. Both the graft and patient survival rates were 85.7% after a median follow-up of 7.8 years. One patient had recurrent hepatitis C virus cirrhosis and recurrent POPH and died from multiorgan failure unrelated to PHT. Four of the remaining 6 patients required oral vasodilator therapy for persistent PHT. Only 2 of the 7 patients (4.4 and 8.5 years after OLT) did not have PHT. In conclusion, patients with POPH responsive to vasodilator therapy may have excellent long-term graft and patient survival after OLT. Despite the alleviation of portal hypertension by OLT, most patients have persistent or recurrent PHT that can be controlled with oral vasodilators. Liver Transpl 20:724-727, 2014. © 2014 AASLD.
Role of cardiac catheterization and percutaneous coronary intervention in the preoperative assessment and management of patients before orthotopic liver transplantation
Authors: Maddur Haripriya , Bourdillon Patrick D. , Liangpunsakul Suthat , Tector Joseph A. , Fridell Jonathan A. , Ghabril Marwan , Lacerda Marco A. , Bourdillon Charlotte , Shen Changyu , Kwo Paul Y.
Published: March 2014

Limited data regarding the optimal risk assessment strategy for evaluating candidates for orthotopic liver transplantation (OLT) exist. Our center has adopted a policy of performing cardiac catheterization (CATH) in patients with predefined risk factors, and this is followed by percutaneous coronary intervention (PCI) when it is indicated, even in the presence of negative stress test findings. The aim of this single-center, retrospective study of all patients who underwent OLT between 2000 and 2010 was to assess the effect of our policy on cardiovascular (CV) complications and survival rates after OLT. Data, including 1-year all-cause and CV mortality, postoperative myocardial infarctions (MIs), and frequencies of CATH and PCI, were abstracted. The study was divided into 3 subperiods to reflect the changes in policy over this period: (A) 2000-2004, (B) 2005-2008, and (C) 2009-2010. One thousand two hundred twenty-one patients underwent OLT between 2000 and 2010. The rate of catheterization increased during the 3 time periods (P < 0.001), as did the rate of PCI (P < 0.05). All-cause mortality decreased over the periods (P < 0.001), as did the MI rate (P < 0.001). Thirty-five of the 57 patients requiring PCI had normal stress tests. The mortality rate associated with postoperative MIs was significantly higher than the overall all-cause mortality rate. In conclusion, a significant improvement in the overall survival rate over the 3 analyzed time periods was noted. Increases in the frequencies of CATH and PCI corresponded to significant reductions in postoperative MIs and 1-year all-cause mortality rates. The increased use of CATH and PCI was associated with reduced overall all-cause mortality through reductions in the incidence of both fatal and nonfatal MIs. Further analyses of the role of stress testing and CATH in evaluating and treating patients before OLT are required to optimize this process. Liver Transpl 20:664-672, 2014. © 2014 AASLD.
Market Power, Efficiencies, and Entry Evidence from an Airline Merger
Authors: Hüschelrath Kai , Müller Kathrin
Published: March 2014

We investigate the competitive effects of the merger between Delta Air Lines and Northwest Airlines (2009) in the domestic US airline industry. Applying fixed‐effects regression models, we find that the transaction led to short‐term price increases of about 11% on overlapping routes and about 10% on routes that experienced a merger‐induced switch of the operating carrier. Over a longer period, however, our estimation results are consistent with the hypothesis that both merger efficiencies and postmerger entry by competitors initiated a downward trend in price, leaving consumers with a small net price increase of about 3% on the affected routes. Copyright © 2014 John Wiley & Sons, Ltd.
Small‐fiber neuropathy with cardiac denervation in postural tachycardia syndrome
Authors: Haensch Carl‐Albrecht , Tosch Marco , Katona Istvan , Weis Joachim , Isenmann Stefan
Published: March 2014

Introduction: Postural tachycardia syndrome (POTS) is a disorder of orthostatic intolerance characterized by excessive tachycardia of unknown etiology. Our objective in this study was to evaluate the correlation between C‐fiber involvement as shown by skin biopsy and adrenergic cardiac metaiodobenzylguanadine (MIBG) uptake in POTS patients. Methods: Skin biopsies of 84 patients with POTS were examined by Protein Gene Product 9.5 (PGP9.5) immunohistochemistry and were compared with MIBG myocardial scintigraphy imaging data. Results: Mean intraepidermal nerve fiber (IENF) density was in the lower normal age‐adjusted range, 7.2 ± 2.9/mm (normal ≥7/mm), and was slightly below the normal range in 45% of POTS patients. MIBG uptake was reduced in 21% of patients. Low IENF density correlated with reduced cardiac MIBG uptake (r = 0.39, P = 0.001). Conclusions: A subset of neuropathic POTS patients may harbor mild small fiber neuropathy with abnormalities of unmyelinated nerve fibers in the skin associated with reduced myocardial postganglionic sympathetic innervation. Muscle Nerve 50: 956–961, 2014
Antibiotic therapy for inpatients with community‐acquired pneumonia in a developing country
Authors: Trinh Hieu T. , Hoang Phuong H. , Cardona‐Morrell Magnolia , Nguyen Hai T. , Vu Dinh Hoa , Dong Phuong T. X. , Cao Thao T. B. , Nguyen Son T. , Pham Van T. T. , Moss Le , Dinh Kathryn , Dartnell Jonathan , Nguyen Huong T. L.
Published: March 2014

Purpose

The aim of this study was to identify antibiotic prescription patterns for community‐acquired pneumonia (CAP) in Vietnam.

Methods

Medical records for CAP adult patients admitted to 10 hospitals across the country were randomly selected from admission lists during the peak pneumonia season. CAP cases were identified from manual record reviews by clinical pharmacists. Data was collected using a standard data collection tool including patient clinical features on admission, comorbidities, microbiological culture results, and antibiotic regimens. Pneumonia severity was estimated using the CURB‐65 score.

Results

A total of 649 medical records for adult patients (55.2% male and 52.3% urban residents, median age 68 years) met the selection criteria for CAP. Pneumonia severity was assessed as mild (64.1% of patients), moderate (23.0%), and severe (9.2%). Antibiotics were most frequently administered intravenously (93.4%) and as combination therapy (dual therapy 54.4%, monotherapy 42.5%, and triple therapy 3.1% of patients) regardless of CAP severity. Third‐generation cephalosporins were used most frequently (29.3% as monotherapy and 40.4% as combination therapy). Third‐generation cephalosporins were most commonly combined with penicillins and/or quinolones.

Conclusions

This first nationwide study provides a baseline profile of antibiotic use in the treatment of CAP. Third‐generation cephalosporins were widely used for initial empirical management of CAP, often in combination with quinolones, regardless of CAP severity. The study will assist in providing an evidence base to inform new national antibiotic guidelines for CAP management and will contribute locally relevant data for the national master plan addressing antibiotic resistance and the development of educational interventions to improve CAP management. Copyright © 2014 John Wiley & Sons, Ltd.
AlGaN/GaN HEMTs on Si by MBE with regrown contacts and fT = 153 GHz
Authors: Ganguly Satyaki , Song Bo , Hwang Wan Sik , Hu Zongyang , Zhu Mingda , Verma Jai , Xing Huili (Grace) , Jena Debdeep
Published: March 2014

AlGaN/GaN high‐electron‐mobility transistors (HEMT) have been grown by radio frequency molecular beam epi‐taxy (RF‐MBE) on 3″ Si substrates. A record low contact resistance Rc ˜ 0.11 Ω.mm has been achieved for GaN HEMTs on Si by using non alloyed ohmic contacts regrown by MBE. Owing to the low contact resistance a 75‐nm gate length unpassivated HEMT shows intrinsic current gain cut‐off frequency fT =153 GHz, a high saturation drain current density> 1.3 A/mm and a low RON of 1 Ω.mm, among the best reported for HEMTs on Si. With further scaling GaN HEMTs on Si can compete in the high‐performance RF arena with similar devices on SiC, while exploiting the many advantages of integration with Si. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Experimental and theoretical study of dephasing processes in the kinetics of photoexcited carriers in GaN
Authors: Garrett Gregory A. , Shishehchi Sara , Rudin Sergey , Malinovsky Vladimir , Wraback Michael , Bellotti Enrico
Published: March 2014

The scattering and dephasing processes that accompany the initial photoexcitation of electron‐hole pairs in the semiconductor GaN are studied by sub‐picosecond time‐resolved photoluminescence. The rise time of the carrier recombination at the band edge after excitation 750 meV above the band gap is analyzed as a function of initial photoexcited carrier density and sample temperature. To elucidate the findings, simulations were performed based on a two band model with a non‐parabolic conduction band and using a generalized Monte‐Carlo technique. Results showed a small dependence in the rise time on the initial carrier density but a strong dependence on the sample temperature, where simulation and experiment scaled proportionately. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Layer‐by‐layer AuCl3 doping of stacked graphene films
Authors: Oh Sooyeoun , Kim Byung‐Jae , Kim Jihyun
Published: March 2014

We investigated the effect of layer‐by‐layer AuCl3 doping on the electrical and optical properties of stacked graphene films. Graphene grown by the chemical‐vapor deposition method on a Cu‐foil was chemically doped by AuCl3 solution with a concentration of 20 mM. Eight different configurations were prepared and analyzed by using four‐point probe measurements, optical transmittance measurements, scanning electron microscopy, and micro‐Raman spectroscopy to compare the optical and electrical characteristics of the different graphene samples. In our study, the top‐layer doping method was very effective because better performances considering both sheet resistance and optical transmittance were observed from the configurations with the top‐layer doped. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Exploring Sialic Acid Receptors‐Related Infection Behavior of Avian Influenza Virus in Human Bronchial Epithelial Cells by Single‐Particle Tracking
Authors: Wang Zhi‐Gang , Liu Shu‐Lin , Zhang Zhi‐Ling , Tian Zhi‐Quan , Tang Hong‐Wu , Pang Dai‐Wen
Published: March 2014

Human respiratory tract epithelial cells are the portals of human infection with influenza viruses. However, the infection pathway of individual avian influenza viruses in human respiratory cells remains poorly reported so far. The single‐particle tracking technique (SPT) is a powerful tool for studying the transport mechanism of biomolecules in live cells. In this work, we use quantum dots to label avian influenza H9N2 virus and elaborate on the infection mechanism of the virus in human bronchial epithelial (HBE) cells using a three‐dimensional SPT technique. We have found that the H9N2 virus can infect HBE cells directly and the virus infection follows an actin filament‐ and microtubule‐dependent process with a three‐stage pattern. The transport behaviors show a high degree of consistency between the sialic acid receptors and the influenza virus. Real‐time SPT provides dynamic evidence of the sialic acid receptors‐related infection behavior of the avian influenza virus in live cells. The study of the influence of sialic acid receptors on virus infection may contribute to a better understanding of the cross‐species transmission of the avian influenza virus.