bluuebunny/crossref_metadata_2025 huggingface dataset:
Site‐Selective and Metal‐Free Aliphatic CH Oxidation Enabled Synthesis of [5,24,25‐D3]‐(25S)‐Δ7‐Dafachronic acid
Authors: Liu Weilong , Li Xiangke , Chen Jie , Li Tiemei , Dong Mengqiu , Lei Xiaoguang
Published: February 2015

Steroid hormones play significant roles in both worms and mammalians. (25S)‐Δ7‐Dafachronic acid (Δ7‐DA, 1) is a member of the dafachronic acid hormonal series that regulates both development and lifespan of C. elegans. Despite its importance, effective tools for the illumination of its mode of action are lacking. Herein, we report an efficient synthesis of trideuterated Δ7‐DA, [5,24,25‐D3]‐(25S)‐Δ7‐dafachronic acid ([D3]‐Δ7‐DA, 2), as a useful chemical tool for subsequent biological studies. Key steps for this bioinspired synthesis approach include site‐selective aliphatic CH oxidation mediated by methyl(trifluoromethyl)dioxirane (TFDO), and the iridium/phosphine‐oxazoline‐catalyzed late‐stage asymmetric deuterium reduction.
Synthesis and Characterization of a Cu14 Hydride Cluster Supported by Neutral Donor Ligands
Authors: Nguyen Thuy‐Ai D. , Goldsmith Bryan R. , Zaman Homaira T. , Wu Guang , Peters Baron , Hayton Trevor W.
Published: February 2015

The copper hydride clusters [Cu14H12(phen)6(PPh3)4][X]2 (X=Cl or OTf; OTf=trifluoromethanesulfonate, phen=1,10‐phenanthroline) are obtained in good yields by the reaction of [(Ph3P)CuH]6 with phen, in the presence of a halide or pseudohalide source. The complex [Cu14H12(phen)6(PPh3)4][Cl]2 reacts with CO2 in CH2Cl2, in the presence of excess Ph3P, to form the formate complex [(Ph3P)2Cu(κ2‐O2CH)], along with [(phen)(Ph3P)CuCl].
A partially linear single‐index transformation model and its nonparametric estimation
Authors: Ding Xiaobo , Zhou Xiao‐Hua , Wang Qihua
Published: February 2015

In this paper, we consider the nonparametric estimation of the partially linear single‐index transformation model, where the transformation function, single‐index function and error distribution are all completely unknown. We first use the minimum average variance estimation method to estimate the regression coefficients, and then propose a new incorporated local linear regression estimator for the derivative function of the single‐index function. Accordingly by integration we can obtain the estimator of the single‐index function. Finally we propose a constrained least square estimator for the transformation function, where basis function approximation is employed and cross validation method is proposed to select suitable sets of basis functions. Asymptotical properties of the estimators are established. Simulation studies show that our proposed estimators work well. A real‐world data analysis of total health care charges was used to illustrate the proposed procedure. The Canadian Journal of Statistics 43: 97–117; 2015 © 2015 Statistical Society of Canada
In Vivo Targeting through Click Chemistry
Authors: Brudno Yevgeny , Desai Rajiv M. , Kwee Brian J. , Joshi Neel S. , Aizenberg Michael , Mooney David J.
Published: February 2015

Targeting small molecules to diseased tissues as therapy or diagnosis is a significant challenge in drug delivery. Drug‐eluting devices implanted during invasive surgery allow the controlled presentation of drugs at the disease site, but cannot be modified once the surgery is complete. We demonstrate that bioorthogonal click chemistry can be used to target circulating small molecules to hydrogels resident intramuscularly in diseased tissues. We also demonstrate that small molecules can be repeatedly targeted to the diseased area over the course of at least one month. Finally, two bioorthogonal reactions were used to segregate two small molecules injected as a mixture to two separate locations in a mouse disease model. These results demonstrate that click chemistry can be used for pharmacological drug delivery, and this concept is expected to have applications in refilling drug depots in cancer therapy, wound healing, and drug‐eluting vascular grafts and stents.
The Unexpected Mechanism Underlying the High‐Valent Mono‐Oxo‐Rhenium(V) Hydride Catalyzed Hydrosilylation of CN Functionalities: Insights from a DFT Study
Authors: Wang Jiandi , Wang Wenmin , Huang Liangfang , Yang Xiaodi , Wei Haiyan
Published: February 2015

In this study, we theoretically investigated the mechanism underlying the high‐valent mono‐oxo‐rhenium(V) hydride Re(O)HCl2(PPh3)2 (1) catalyzed hydrosilylation of CN functionalities. Our results suggest that an ionic SN2‐Si outer‐sphere pathway involving the heterolytic cleavage of the SiH bond competes with the hydride pathway involving the CN bond inserted into the ReH bond for the rhenium hydride (1) catalyzed hydrosilylation of the less steric CN functionalities (phenylmethanimine, PhCH=NH, and N‐phenylbenzylideneimine, PhCH=NPh). The rate‐determining free‐energy barriers for the ionic outer‐sphere pathway are calculated to be ∼28.1 and 27.6 kcal mol−1, respectively. These values are slightly more favorable than those obtained for the hydride pathway (by ∼1–3 kcal mol−1), whereas for the large steric CN functionality of N,1,1‐tri(phenyl)methanimine (PhCPh=NPh), the ionic outer‐sphere pathway (33.1 kcal mol−1) is more favorable than the hydride pathway by as much as 11.5 kcal mol−1. Along the ionic outer‐sphere pathway, neither the multiply bonded oxo ligand nor the inherent hydride moiety participate in the activation of the SiH bond.
Oxidation‐State Analysis of Ceria by X‐ray Photoelectron Spectroscopy
Authors: Allahgholi Aschkan , Flege J. Ingo , Thieß Sebastian , Drube Wolfgang , Falta Jens
Published: February 2015

Three different methods to determine the oxide‐phase concentration in mixed cerium oxide by hard X‐ray photoelectron spectroscopy are applied and quantitatively compared. Synchrotron‐based characterization of the O 1s region was used as a benchmark to introduce a method based on the weighted superposition of the Ce 3d spectra of the pure Ce3+ and Ce4+ phases, which was shown to lead to reliable and highly accurate determination of the mean oxidation state in mixed cerium oxides. The results obtained reveal a linear relation between the third distinct final state (u′′′) satellite peak intensity of the Ce4+ phase and the Ce4+ concentration by proper inclusion of Ce3+‐related plasmon satellite peaks, which contradicts previous claims of nonlinear behavior. In contrast, quantitative conventional peak‐fitting procedures were shown to be well suited for the Ce 2p region due to its relatively simple structure. Additional satellite features observed in the Ce 3d spectrum of CeO2 were proposed to originate from plasmon contributions.
Commentary on “Caged Phosphate and the Slips and Misses in Determination of Quantum Yields for Ultraviolet‐A‐Induced Photouncaging” by G. Gasser and Co‐Workers
Authors: Corrie John E. T. , Kaplan Jack H. , Forbush Biff , Ogden David C. , Trentham David R.
Published: February 2015

Commentary on “Caged Phosphate and the Slips and Misses in Determination of Quantum Yields for Ultraviolet‐A‐Induced Photouncaging” by G. Gasser and Co‐Workers (ChemPhysChem 2015, 16, 1857–1860).
Modification of the Optical Spectrum of Cytosine by the Formation of an Ordered Monolayer of Molecules at a Au(110)/Electrolyte Interface
Authors: Bowfield Andrew , Smith Caroline I. , Mansley Christopher P. , Weightman Peter
Published: February 2015

An analysis of the reflection anisotropy spectrum (RAS) of an ordered monolayer of cytosine adsorbed at a Au(110)/electrolyte interface is found to contain optical contributions from both the substrate and the cytosine. The spectrum of cytosine in an aqueous environment is significantly broadened by the interaction between the molecule and the Au(110). Successful simulations of the Au(110)/cytosine interface consisting of two additional molecular transitions, which sit in the middle of previously observed molecular absorption bands, are produced by an empirical Lorentzian transition model that is consistent with previous theoretical and experimental studies. While this analysis alone cannot determine the number of π→π* dipole transitions, it confirms that the only cytosine transitions that contribute to the optical response of the Au(110)/cytosine interface are located in the plane of the molecule, which is vertical to the gold surface with the long axis along the [1$\bar 1$0] direction.
Surface Trapping and STM Observation of Conformational Isomers of a Bis(Terpyridine) Ligand from Metallosupramolecular Grids
Authors: Karan Sujoy , Hamann Christian , Tang Hao , Stefankiewicz Artur R. , Lehn Jean‐Marie , Berndt Richard
Published: February 2015

Tetranuclear Co‐grid complexes incorporating bis‐tridentate ligands, namely 4,6‐bis(2,2′‐bipyrid‐6‐yl)‐2‐phenylpyrimidine, were electrosprayed onto a Au(111) substrate under an ultrahigh vacuum. Fragmentation occurs leaving the ligands in four different conformations. Most ligands are found to form H‐bonded dimers. The most abundant conformer of the ligand on the Au surface is an asymmetric form, which has not been observed before. The present results indicate that the fragmentation of coordination compounds during the deposition process, in principle, allows for surface trapping, identification, and investigation of high energy, out‐of‐equilibrium conformations of the ligand molecules at low temperatures, which otherwise would not be observable.
Translational aspects of blood–brain barrier transport and central nervous system effects of drugs: From discovery to patients
Authors: de Lange ECM , Hammarlund‐Udenaes M
Published: February 2015

The development of CNS drugs is associated with high failure rates. It is postulated that too much focus has been put on BBB permeability and too little on understanding BBB transport, which is the main limiting factor in drug delivery to the brain. An integrated approach to collecting, understanding, and handling pharmacokinetic‐pharmacodynamic information from early discovery stages to the clinic is therefore recommended in order to improve translation to human drug treatment.
Xylose Isomerization with Zeolites in a Two‐Step Alcohol–Water Process
Authors: Paniagua Marta , Saravanamurugan Shunmugavel , Melian‐Rodriguez Mayra , Melero Juan A. , Riisager Anders
Published: February 2015

Isomerization of xylose to xylulose was efficiently catalyzed by large‐pore zeolites in a two‐step methanol–water process that enhanced the product yield significantly. The reaction pathway involves xylose isomerization to xylulose, which, in part, subsequently reacts with methanol to form methyl xyluloside (step 1) followed by hydrolysis after water addition to form additional xylulose (step 2). NMR spectroscopy studies performed with 13C‐labeled xylose confirmed the proposed reaction pathway. The most active catalyst examined was zeolite Y, which proved more active than zeolite beta, ZSM‐5, and mordenite. The yield of xylulose obtained over H‐USY (Si/Al=6) after 1 h of reaction at 100 °C was 39 %. After water hydrolysis in the second reaction step, the yield increased to 47 %. Results obtained from pyridine adsorption studies confirm that H‐USY (6) is a catalyst that combines Brønsted and Lewis acid sites, and isomerizes xylose in alcohol media to form xylulose at low temperature. The applied zeolites are commercially available; do not contain any auxiliary tetravalent metals, for example, tin, titanium, or zirconium; isomerize xylose efficiently; are easy to regenerate; and are prone to recycling.
Electrifying White Biotechnology: Engineering and Economic Potential of Electricity‐Driven Bio‐Production
Authors: Harnisch Falk , Rosa Luis F. M. , Kracke Frauke , Virdis Bernardino , Krömer Jens O.
Published: February 2015

Invited for the cover of this issue are the groups of Falk Harnisch at the Helmholtz Centre for Environmental Research (Germany) and his collaboration partners at The University of Queensland (Australia). The image depicts their vision of the world, if “electrification” of white biotechnology comes true. The Concept itself is available at 10.1002/cssc.201402736.
Provide access to internships across the college curriculum
Authors: Rossi‐Le Laura
Published: February 2015

As the controversy surrounding unpaid internships continues to simmer, the value of the internship as a vital steppingstone in the career path of today's college graduates remains constant, with increasing numbers of colleges and universities offering the internship, both paid and unpaid, as a curricular option. In response to the concerns of employers over the issue of intern compensation, the U.S. Department of Labor has established a set of clarifying criteria for private‐sector organizations, emphasizing that internships must benefit the student and constitute an integral part of an institution's academic programming.
Student‐centered approach helps program survive in changing landscape
Authors: Gomez Cynthia
Published: February 2015

Louis deSalle was working on his doctoral degree when he stumbled onto an opportunity to co‐teach a course for retirees offered by The College of New Rochelle. “I was 28 years old teaching people in their sixties, so I was sort of like their child,” he joked. He immediately fell in love with adult learners.
Potential for adaptive evolution at species range margins: contrasting interactions between red coral populations and their environment in a changing ocean
Authors: Ledoux Jean‐Baptiste , Aurelle Didier , Bensoussan Nathaniel , Marschal Christian , Féral Jean‐Pierre , Garrabou Joaquim
Published: February 2015

Studying population‐by‐environment interactions (PEIs) at species range margins offers the opportunity to characterize the responses of populations facing an extreme regime of selection, as expected due to global change. Nevertheless, the importance of these marginal populations as putative reservoirs of adaptive genetic variation has scarcely been considered in conservation biology. This is particularly true in marine ecosystems for which the deep refugia hypothesis proposes that disturbed shallow and marginal populations of a given species can be replenished by mesophotic ones. This hypothesis therefore assumes that identical PEIs exist between populations, neglecting the potential for adaptation at species range margins. Here, we combine reciprocal transplant and common garden experiments with population genetics analyses to decipher the PEIs in the red coral, Corallium rubrum. Our analyses reveal partially contrasting PEIs between shallow and mesophotic populations separated by approximately one hundred meters, suggesting that red coral populations may potentially be locally adapted to their environment. Based on the effective population size and connectivity analyses, we posit that genetic drift may be more important than gene flow in the adaptation of the red coral. We further investigate how adaptive divergence could impact population viability in the context of warming and demonstrate differential phenotypic buffering capacities against thermal stress. Our study questions the relevance of the deep refugia hypothesis and highlights the conservation value of marginal populations as a putative reservoir of adaptive genetic polymorphism.
Nanopipet‐Based Resistive Pulse Sensing to Follow Alterations in the Size and Concentration of Nanoparticles During Membrane Filtration
Authors: Terejánszky Péter , Makra István , Lukács Alda , Gyurcsányi Róbert E.
Published: February 2015

We propose a calibration‐free resistive pulse sensing (RPS) methodology based on nanopipets to follow the size and concentration changes of nanoparticles during size‐selective separation processes. The study was performed with monodisperse latex nanoparticles and their mixtures that were subjected to separation procedures such as filtration through track‐etch membranes of various pore diameters as well as centrifugal filtration. The RPS measurements were found to be suitable to determine both the recovery of the nanoparticles after filtration as well as subtle changes in their size distribution. Filtration through track‐etch membranes preserved the mean size of the nanoparticles while their recovery was affected by the size of the pore and coexistence of larger nanoparticle fractions in the sample. Centrifugal filtration resulted in the appearance of aggregates.
Obama pledges student privacy protection in State of the Union address
Authors: Hope Joan
Published: February 2015

Safeguarding student privacy is a critical part of your job as an enrollment manager. And it's a big enough issue that President Barack Obama discussed his initiatives to protect student privacy in his State of the Union address.
Achieve greater career success with strategic planning
Authors: Santovec Mary Lou
Published: February 2015

Although success does sometimes happen purely by accident, there are ways to intentionally design it. That's according to Denise Upah Mills, the co‐founder and chief mindset officer of www.leaderfuelnow.com (LFN), a leadership consulting firm based in Kansas City, Mo. If you're still climbing the career ladder, her strategies could help you get where you're going faster.
Enhanced Production of Cellulase from Bacillus licheniformis K‐3 with Potential for Saccharification of Rice Straw
Authors: Gupta Mahak , Sharma Mukul , Singh Satbir , Gupta Puneet , Bajaj Bijender Kumar
Published: February 2015

The unavailability of process‐suitable cellulases and expensive cost prompted research on the economic production of proficient enzymes. Bacillus licheniformis K‐3, an isolate from degrading lignocellulosic biomass, can produce cellulose, possessing activity and stability over broad pH range (4.0–10) and at elevated temperature (40–90 °C). B. licheniformis K‐3 can be used to successfully utilize agricultural residues (such as wheat bran, corn waste, wheat straw, almond hulls, soybean meal, and mustard cake) as substrates for growth and cellulase production. The most effective fermentation variables (wheat bran, incubation time, and medium pH) have been earmarked on the basis of Plackett–Burman designed experiments and they were optimized by using response surface methodology to achieve a 7‐fold enhancement in the cellulase yield. Partially purified cellulase showed efficient saccharification potential for single‐phase sulphuric‐acid‐pretreated rice straw.
Transcriptional profiling of the soil invertebrate Folsomia candida in pentachlorophenol-contaminated soil
Authors: Qiao Min , Wang Guang-Peng , Zhang Cai , Roelofs Dick , van Straalen Nico M. , Zhu Yong-Guan
Published: February 2015

Pentachlorophenol (PCP), a widely used pesticide, is considered to be an endocrine disruptor. The molecular effects of chemicals with endocrine-disrupting potential on soil invertebrates are largely unknown. In the present study, the authors explored the transcriptional expression changes of collembola (Folsomia candida) in response to PCP contamination. A total of 92 genes were significantly differentially expressed at all exposure times, and the majority of them were found to be downregulated. In addition to the transcripts encoding cytochrome P450s and transferase enzymes, chitin-binding protein was also identified in the list of common differentially expressed genes. Analyses of gene ontology annotation and enrichment revealed that cell cycle-related transcripts were significantly induced by PCP, indicating that PCP can stimulate cell proliferation in springtail, as has been reported in human breast cancer cells. Enrichment of functional terms related to steroid receptors was observed, particularly in 20 significant differentially expressed genes involved in chitin metabolism in response to PCP exposure. Combined with confirmation by quantitative polymerase chain reaction, the results indicate that the adverse effects on reproduction of springtails after exposure to PCP can be attributed to a chemical-induced delay in the molting cycle and that molting-associated genes may serve as possible biomarkers for assessing toxicological effects. Environ Toxicol Chem 2015;34:1362–1368. © 2015 SETAC
Banana leaf and glucose mineralization and soil organic matter in microhabitats of banana plantations under long-term pesticide use
Authors: Blume Elena , Reichert José Miguel
Published: February 2015

Soil organic matter (SOM) and microbial activity are key components of soil quality and sustainability. In the humid tropics of Costa Rica 3 pesticide regimes were studied—fungicide (low input); fungicide and herbicide (medium input); and fungicide, herbicide, and nematicide (high input)—under continuous banana cultivation for 5 yr (young) or 20 yr (old) in 3 microhabitats—nematicide ring around plants, litter pile of harvested banana, and bare area between litter pile and nematicide ring. Soil samples were incubated sequentially in the laboratory: unamended, amended with glucose, and amended with ground banana leaves. Soil organic matter varied with microhabitat, being greatest in the litter pile, where microbes had the greatest basal respiration with ground banana leaf, whereas microbes in the nematicide ring had the greatest respiration with glucose. These results suggest that soil microbes adapt to specific microhabitats. Young banana plantations had similar SOM compared with old plantations, but the former had greater basal microbial respiration in unamended and in glucose-amended soil and greater first-order mineralization rates in glucose-amended soil, thus indicating soil biological quality decline over time. High pesticide input did not decrease microbial activity or mineralization rate in surface soil. In conclusion, microbial activity in tropical volcanic soil is highly adaptable to organic and inorganic inputs. Environ Toxicol Chem 2015;34:1232–1238. © 2015 SETAC
Five Tips for Building Strong and Enduring Customer Relationships
Authors: Oberle Chris
Published: February 2015

Contrary to what many pundits say about utilities' inability to provide service levels rivaling those of other types of providers, utility companies actually perform relatively well on standard metrics used to measure loyalty and satisfaction among consumers. However, while these metrics tend to reflect and reward strong operational performance, an area that has been the primary focus of utility companies for many years, these metrics do not necessarily capture the full essence of the relationship or the extent to which customers feel connected to and engaged with their local utility company.
Direct Toll‐Like Receptor 8 signaling increases the functional avidity of human CD8+ T lymphocytes generated for adoptive T cell therapy strategies
Authors: Chatillon Jean‐François , Hamieh Mohamad , Bayeux Florence , Abasq Claire , Fauquembergue Emilie , Drouet Aurélie , Guisier Florian , Latouche Jean‐Baptiste , Musette Philippe
Published: February 2015

Adoptive transfer of in vitro activated and expanded antigen‐specific cytotoxic T lymphocytes (CTLs) is a promising therapeutic strategy for infectious diseases and cancers. Obtaining in vitro a sufficient amount of highly specific cytotoxic cells and capable of retaining cytotoxic activity in vivo remains problematic. We studied the role of Toll‐Like Receptor‐8 (TLR8) engagement on peripheral CTLs activated with melanoma antigen MART‐1‐expressing artificial antigen‐presenting cells (AAPCs). After a 3‐week co‐culture, 3–27% of specific CTLs were consistently obtained. CTLs expressed TLR8 in the intracellular compartment and at the cell surface. Specific CTLs activated with a TLR8 agonist (CL075) 24 h before the end of the culture displayed neither any change in their production levels of molecules involved in cytotoxicity (IFN‐γ, Granzyme B, and TNF‐α) nor major significant change in their cell surface phenotype. However, these TLR8‐stimulated lymphocytes displayed increased cytotoxic activity against specific peptide‐pulsed target cells related to an increase in specific anti‐melanoma CTL functional avidity. TLR8 engagement on CTLs could, therefore, be useful in different immunotherapy strategies.
Electron Transport Mediated by Peptides Immobilized on Surfaces
Authors: Juhaniewicz Joanna , Pawlowski Jan , Sek Slawomir
Published: February 2015

Electron transfer reactions in proteins and peptides are crucial for biological energy conversion. Therefore, an important goal of fundamental research is to provide scientific insight into the mechanisms determining the bridge‐mediated electron transport. One of the main tasks is to understand how the efficiency of this process is affected by the particular structure of a peptide, as well as the surrounding environment, and eventually, how we can control it by means of external chemical and physical factors. The latter could be of crucial importance for the design and development of biosensors and other functional devices, which may benefit from the unique electron transfer properties of peptides. Monolayers immobilized on solid surfaces seem to be particularly useful for that purpose. In this paper, we present the progress of fundamental research related to electron transport through peptides adsorbed onto metal surfaces. Specifically, we have focused on electrochemical studies and nanoscale molecular junction approaches. We have critically reviewed existing data and discussed the discrepancies in the measured efficiencies of electron transport. Some suggestions for future fundamental research in this area are provided. In particular, the need to combine the electrochemical and molecular junction approaches to explore the conductance behavior of peptides under full electrochemical control is emphasized. Some potential applications of peptide monolayers, which take advantage of the unique electrical properties of these compounds, are also discussed.
Understanding What Students Know
Authors: Castek Jill , Coiro Julie
Published: February 2015

This piece is framed by questions we are often asked when we talk about online reading assessments and instruction with teachers. We begin with some of the lessons we have learned in our own experiences with designing measures of online reading comprehension. Then we share our thoughts about key design considerations as well as some of the biggest challenges of trying to capture online research and reading skills when online texts and authentic tasks are constantly changing. By sharing these perspectives, we hope to inspire new ways of tracking students’ progress that can help teachers design powerful literacy instruction that integrates digital texts and new technologies.
Identification of Spatial Durbin Panel Models
Authors: Lee Lung‐fei , Yu Jihai
Published: February 2015

This paper considers identification of spatial Durbin dynamic panel models under 2SLS and ML estimations. We show that the parameters are generally identified via 2SLS moment relations or expected log‐likelihood or quasi‐likelihood functions. Monte Carlo experiments suggest that omitting relevant Durbin terms can result in significant biases in regression estimates, while including an irrelevant Durbin term causes no obvious loss of efficiency. Empirical illustration of the international spillover of economic growth through bilateral trade shows that inclusion of Durbin terms can be important. Copyright © 2015 John Wiley & Sons, Ltd.
ER Stress During the Pubertal Growth Spurt Results in Impaired Long-Bone Growth in Chondrocyte-Specific ERp57 Knockout Mice
Authors: Linz Andrea , Knieper Yvonne , Gronau Tobias , Hansen Uwe , Aszodi Attila , Garbi Natalio , Hämmerling Günter J , Pap Thomas , Bruckner Peter , Dreier Rita
Published: February 2015

Long-bone growth by endochondral ossification is cooperatively accomplished by chondrocyte proliferation, hypertrophic differentiation, and appropriate secretion of collagens, glycoproteins, and proteoglycans into the extracellular matrix (ECM). Before folding and entering the secretory pathway, ECM macromolecules in general are subject to extensive posttranslational modification, orchestrated by chaperone complexes in the endoplasmic reticulum (ER). ERp57 is a member of the protein disulfide isomerase (PDI) family and facilitates correct folding of newly synthesized glycoproteins by rearrangement of native disulfide bonds. Here, we show that ERp57-dependent PDI activity is essential for postnatal skeletal growth, especially during the pubertal growth spurt characterized by intensive matrix deposition. Loss of ERp57 in growth plates of cartilage-specific ERp57 knockout mice (ERp57 KO) results in ER stress, unfolded protein response (UPR), reduced proliferation, and accelerated apoptotic cell death of chondrocytes. Together this results in a delay of long-bone growth with the following characteristics: (1) enlarged growth plates; (2) expanded hypertrophic zones; (3) retarded osteoclast recruitment; (4) delayed remodeling of the proteoglycan-rich matrix; and (5) reduced numbers of bone trabeculae. All the growth plate and bone abnormalities, however, become attenuated after the pubertal growth spurt, when protein synthesis is decelerated and, hence, ERp57 function is less essential. © 2015 American Society for Bone and Mineral Research.
Nexavar/Stivarga and Viagra Interact to Kill Tumor Cells
Authors: Tavallai Mehrad , Hamed Hossein A. , Roberts Jane L. , Cruickshanks Nichola , Chuckalovcak John , Poklepovic Andrew , Booth Laurence , Dent Paul
Published: February 2015

We determined whether the multi‐kinase inhibitor sorafenib or its derivative regorafenib interacted with phosphodiesterase 5 (PDE5) inhibitors such as Viagra (sildenafil) to kill tumor cells. PDE5 and PDGFRα/β were over‐expressed in liver tumors compared to normal liver tissue. In multiple cell types in vitro sorafenib/regorafenib and PDE5 inhibitors interacted in a greater than additive fashion to cause tumor cell death, regardless of whether cells were grown in 10 or 100% human serum. Knock down of PDE5 or of PDGFRα/β recapitulated the effects of the individual drugs. The drug combination increased ROS/RNS levels that were causal in cell killing. Inhibition of CD95/FADD/caspase 8 signaling suppressed drug combination toxicity. Knock down of ULK‐1, Beclin1, or ATG5 suppressed drug combination lethality. The drug combination inactivated ERK, AKT, p70 S6K, and mTOR and activated JNK. The drug combination also reduced mTOR protein expression. Activation of ERK or AKT was modestly protective whereas re‐expression of an activated mTOR protein or inhibition of JNK signaling almost abolished drug combination toxicity. Sildenafil and sorafenib/regorafenib interacted in vivo to suppress xenograft tumor growth using liver and colon cancer cells. From multiplex assays on tumor tissue and plasma, we discovered that increased FGF levels and ERBB1 and AKT phosphorylation were biomarkers that were directly associated with lower levels of cell killing by ‘rafenib + sildenafil. Our data are now being translated into the clinic for further determination as to whether this drug combination is a useful anti‐tumor therapy for solid tumor patients. J. Cell. Physiol. 230: 2281–2298, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.
Frequency of recommendations for additional imaging in diagnostic ultrasound examinations: Evaluation of radiologist, technologist, and other examination‐related factors
Authors: Margolis Nathaniel E. , Rosenkrantz Andrew B. , Babb James S. , Macari Michael
Published: February 2015

Objective

Our aim in this study was to evaluate the effect of the radiologist, technologist, and other examination‐related factors on the frequency of recommendations for additional imaging (RAI) during sonographic (US) interpretation.

Methods

We retrospectively reviewed 719 US reports from a single academic medical center for the presence of RAI. All studies had been interpreted by one of three abdominal radiologists. Examinations were performed at an outpatient radiology facility with no onsite radiologist (n = 299) or at an inpatient emergency department or hospital‐based outpatient setting that had an onsite radiologist (n = 420). Possible associations between the frequency of RAI and the presence of an onsite radiologist, location of the examination, body part or region imaged, patient age, technologist performing the exam, and radiologist reading the exam were evaluated.

Results

There were significant differences between each pair of radiologists in terms of overall frequency of RAI (p < 0.001) (radiologist 1: 12.0% [22/184]; radiologist 2: 21.6% [78/361]; and radiologist 3: 45.5% [79/174]). In addition, there were statistically significant differences in the frequency of RAI among studies scanned by the 10 different US technologists (13.6%–40.0%, p = 0.03). However, other factors such as patient age, patient sex, US unit, patient location, and radiologist location were not associated with the frequency of RAI (p = 0.15–0.93).

Conclusions

The individual radiologist and technologist influenced the frequency of RAI for US examinations, whereas other examination‐related factors did not. The observed substantial variability in RAI between radiologists and technologists warrants further study, with consideration of strategies to optimize RAI within US reports. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 43:463–468 2015
Efficient tryptophan‐catabolizing activity is consistently conserved through evolution of TDO enzymes, but not IDO enzymes
Authors: Yuasa Hajime J. , Ball Helen J.
Published: February 2015

Indoleamine 2,3‐dioxygenase (IDO) and tryptophan 2,3‐dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L‐Trp) through the kynurenine pathway. TDO is found in almost all metazoan and many bacterial species, but not in fungi. We show that TDO enzymes have high catalytic‐efficiency for L‐Trp catabolism, regardless of their biological origin, suggesting that TDO has been an L‐Trp‐specific degrading enzyme throughout its evolution. Meanwhile, IDO was initially discovered in mammals, and subsequently has been found in lower vertebrates, several invertebrates, fungi and a number of bacterial species. Some lineages have independently generated multiple IDO paralogues through gene duplications. Interestingly, only mammalian IDO1s and fungal “typical” IDOs have high affinity and catalytic efficiency for L‐Trp catabolism, comparable to TDOs. We show that invertebrate IDO enzymes have low affinity and catalytic efficiency for L‐Trp catabolism. We suggest that the phylogenetic distribution of “low catalytic‐efficiency IDOs” indicates the ancestral IDO also had low affinity and catalytic efficiency for L‐Trp catabolism. IDOs with high catalytic‐efficiency for L‐Trp‐catabolism may have evolved in certain lineages to fulfill particular biological roles. The low catalytic‐efficiency IDOs have been well conserved in a number of lineages throughout their evolution, although it is not clear that the enzymes contribute significantly to L‐Trp catabolism in these species. Investigation of other substrates and functions of the ancestral IDO and low catalytic efficiency IDOs may identify additional biological roles for these enzymes. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 128–140, 2015. © 2015 Wiley Periodicals, Inc.
Oxygen and redox potential gradients in the rhizosphere of alfalfa grown on a loamy soil
Authors: Uteau Daniel , Hafner Silke , Pagenkemper Sebastian Kouso , Peth Stephan , Wiesenberg Guido L. B. , Kuzyakov Yakov , Horn Rainer
Published: February 2015

Oxygen (O2) supply and the related redox potential (EH) are important parameters for interactions between roots and microorganisms in the rhizosphere. Rhizosphere extension in terms of the spatial distribution of O2 concentration and EH is poorly documented under aerobic soil conditions. We investigated how far O2 consumption of roots and microorganisms in the rhizosphere is replenished by O2 diffusion as a function of water/air‐filled porosity. Oxygen concentration and EH in the rhizosphere were monitored at a mm‐scale by means of electroreductive Clark‐type sensors and miniaturized EH electrodes under various matric potential ranges. Respiratory activity of roots and microorganisms was calculated from O2 profiles and diffusion coefficients. pH profiles were determined in thin soil layers sliced near the root surface.

Gradients of O2 concentration and the extent of anoxic zones depended on the respiratory activity near the root surface. Matric potential, reflecting air‐filled porosity, was found to be the most important factor affecting O2 transport in the rhizosphere. Under water‐saturated conditions and near field capacity up to –200 hPa, O2 transport was limited, causing a decline in oxygen partial pressures (pO2) to values between 0 and 3 kPa at the root surface. Aerobic respiration increased by a factor of 100 when comparing the saturated with the driest status. At an air‐filled porosity of 9% to 12%, diffusion of O2 increased considerably. This was confirmed by EH around 300 mV under aerated conditions, while EH decreased to 100 mV on the root surface under near water‐saturated conditions. Gradients of pO2 and pH from the root surface indicated an extent of the rhizosphere effect of 10–20 mm. In contrast, EH gradients were observed from 0 to 2 mm from the root surface. We conclude that the rhizosphere extent differs for various parameters (pH, Eh, pO2) and is strongly dependent on soil moisture.
The effect of dairy sewage sludge amendment on repellency and hydraulic conductivity of soil aggregates from two depths of Eutric Cambisol
Authors: Król Anna , Lipiec Jerzy , Frąc Magdalena
Published: February 2015

Appropriate management of sewage sludge is an important worldwide issue due to the still growing amount of wastewaters. In the study we examined to what extent the addition of dairy sewage sludge compared with mineral fertilization affects porosity, repellency index, and hydraulic conductivity of variously sized aggregates from two soil depths of Eutric Cambisol derived from loess: 5–15 cm and 25–35 cm. The repellency index was calculated as a ratio of ethanol and water sorptivity. Data on water and ethanol sorptivities of initially air‐dry soil aggregate fractions were obtained from steady state flow measurements using an infiltration device. Hydraulic conductivity was determined by measuring water infiltration at five pressure heads: –8, –6, –4, –2, and 0 cm of water column with the same device as for sorptivity determination. Addition of sewage sludge to the soil decreased the soil repellency index by an average of 27% in topsoil and 32% in subsoil for both aggregate sizes, respectively, and increased hydraulic conductivity about four times in both layers. Smaller aggregates (15–20 mm diameter) from soil amended with sewage sludge, in comparison with larger ones (30–35 mm diameter), had a higher repellency index by 36 and 24% in topsoil and subsoil, respectively. As for aggregates from soil with mineral fertilization, those differences were smaller and equal to 15% in subsoil, in topsoil smaller aggregates even had slightly lower repellency index (by 5%). Aggregates taken from the upper soil layer were more water repellent and had smaller hydraulic conductivity than those taken from subsoil, regardless of soil treatment and aggregate size.
Endoscopic transcanal corridors to the lateral skull base: Initial experiences
Authors: Marchioni Daniele , Alicandri‐Ciufelli Matteo , Rubini Alessia , Presutti Livio
Published: February 2015

Objectives/Hypothesis

Surgical approaches to the lateral skull base, internal auditory canal (IAC), and petrous bone are widely known and have been extensively recorded. Despite the benign nature and limited dimensions of lesions located in this anatomical region, extirpative surgical approaches are often required to reach and remove the disease. The aim of present report was to describe our initial experiences with minimally invasive endoscopic approaches to the lateral skull base.

Study Design

Retrospective review of patients' charts and video recordings from surgery.

Methods

Twelve patients were included in the study. Three main corridors to the lateral skull base were identified: the transcanal suprageniculate corridor, the transcanal transpromontorial corridor, and the transcanal infracochlear corridor. Landmarks, tips, and pitfalls of the approaches have been reviewed and highlighted.

Results

These corridors provide a direct approach to pathology involving the fundus, IAC, cochlea, petrous apex and geniculate ganglion region, without any external incision. The pathology was successfully removed in most cases with no important postoperative complications and reasonable facial nerve outcomes.

Conclusions

The transcanal endoscopic approaches to the lateral skull base proved to be successful for pathology removal involving the fundus, IAC, cochlea, petrous apex, and geniculate ganglion region. Future widespread application of this kind of approach in lateral skull base surgery will depend on the development of technology, and surgical and anatomical refinements.

Level of Evidence

4. Laryngoscope, 125:S1–S13, 2015
A ten‐year review of soft tissue reactions around percutaneous titanium implants for auricular prosthesis
Authors: Tzortzis Sevasti , Tzifa Konstantina , Tikka Theofano , Worrollo Steve , Williams Joanne , Reid Andrew P. , Proops David
Published: February 2015

Objectives/Hypothesis

Soft tissue reactions around abutments are the most common complications of percutaneous osseointegrated implants. The main objective of this study was to review our series of osseointegrated implants, evaluate the degree of adverse skin reactions around the auricular abutments, and compare with skin reactions in the pediatric bone‐anchored hearing aid (BAHA) population. The reason for comparing these two groups was the difference in abutment shape and position in skin with different characteristics.

Study Design

A retrospective case analysis of 131 patient notes.

Methods

We retrospectively studied 131 pediatric and adult patients who underwent an osseointegrated auricular prosthesis over a 10‐year period (1997–2007).

Results

There were 95 adults and 36 children who had been implanted and fitted with an auricular prosthesis during the 10‐year study period. All patients were followed up postoperatively for a 2‐year minimum up to a 14‐year maximum follow‐up. Thirteen (13/36, 36%) children and seven adults (7/95, 7%) had a skin reaction around the ear prosthesis.

Conclusions

The literature review has supported our study results and has shown that children have higher skin reactions in both BAHA and auricular prostheses than adults. Adverse skin reactions in the pediatric auricular group were significantly lower that the pediatric BAHA group.

Level of Evidence

4 Laryngoscope, 125:1934–1939, 2015
Detection of ideal reservoir level after laryngectomy using endoilluminator in voice rehabilitation
Authors: Sirin Ali Ahmet , Erdim Ibrahim , Baykal Bahadir , Oghan Fatih , Yilmazer Rasim , Guvey Ali , Kayhan Fatma Tulin
Published: February 2015

Objective

To assess the diagnostic value of a novel device, the endoilluminator, in patients who can or cannot attain effective speech after application of voice prosthesis.

Study Design

Prospective clinical study.

Methods

Thirty‐four patients who underwent total laryngectomy and whose insufflation test was positive were included. As a result of efforts to develop an insufflation test that includes a light apparatus, we attained a device that we call an endoilluminator. We found that the area it illuminated when a patient achieved effective speech was a predictive factor for the test result. That is, patients for whom the upper part of the tracheostomy (where the standard tracheoesophageal fistula will be opened) was illuminated were categorized as the positive test group, whereas those for whom the neck skin above this region was illuminated were categorized as the negative test group.

Results

In 27 of the 34 patients, appropriate localization was determined using the endoilluminator, and these patients achieved effective speech. In the remaining seven patients, localization was inappropriate and they did not achieve effective speech during the first week, first month, or third month postpuncture. In further investigations of these seven patients, a pharyngoesophageal spasm was detected in five, and a pharyngoesophageal stricture was detected in two.

Conclusion

Endoilluminator increases the success rate of the insufflation test by accurately predicting a patient's ability to achieve effective speech after application of voice prosthesis.

Level of Evidence

4. Laryngoscope, 125:E239–E244, 2015
Formation of DNA‐Copolymer Fibrils Through an Amyloid‐Like Nucleation Polymerization Mechanism
Authors: Kedracki Dawid , Filippov Sergey K. , Gour Nidhi , Schlaad Helmut , Nardin Corinne
Published: February 2015

Conjugation of a hydrophobic poly(2‐oxazoline) bearing tertiary amide groups along its backbone with a short single stranded nucleotide sequence results in an amphiphilic comb/graft copolymer, which organizes in fibrils upon direct dissolution in water. Supported by circular dichroism, atomic force microscopy, transmission electron microscopy, and scattering data, fibrils are formed through inter‐ and intramolecular hydrogen bonding between hydrogen accepting amide groups along the polymer backbone and hydrogen donating nucleic acid grafts leading to the formation of hollow tubes.

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Screening Chemicals for Receptor‐Mediated Toxicological and Pharmacological Endpoints: Using Public Data to Build Screening Tools within a KNIME Workflow
Authors: Steinmetz F. P. , Mellor C. L. , Meinl T. , Cronin M. T. D.
Published: February 2015

Assessing compounds for their pharmacological and toxicological properties is of great importance for industry and regulatory agencies. In this study an approach using open source software and open access databases to build screening tools for receptor‐mediated effects is presented. The retinoic acid receptor (RAR), as a pharmacologically and toxicologically relevant target, was chosen for this study. RAR agonists are used in the treatment of a number of dermal conditions and specific types of cancer, such as acute promyelocytic leukemia. However, when administered chronically, there is strong evidence that RAR agonists cause hepatosteatosis and liver injury. After compiling information on ligand‐protein‐interactions, common substructures and physico‐chemical properties of ligands were identified manually and coded into SMARTS strings. Based on these SMARTS strings and calculated physico‐chemical features, a rule‐based screening workflow was built within the KNIME platform. The workflow was evaluated on two datasets: one with RAR agonists exclusively and another large, chemically diverse dataset containing only a few RAR agonists. Possible modifications and applications of screening workflows, dependent on their purpose, are presented.