bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiography and biomechanics of sixth and seventh cervical vertebrae segments after disc fenestration and after insertion of an intervertebral body spacer
Authors: Desquilbet L. , Fitzpatrick D. , Bernard F. , Moissonnier P.
Published: October 2013

Objectives: To study the radiographic characteristics and the biomechanical properties of the sixth and seventh cervical (C6–C7) vertebral motion unit (VMU) with an intact disc, after disc fenestration, and after placement of an intervertebral body spacer (IVBS).

Methods: Six cadaveric C6-C7 VMU were retrieved from six Greyhound cadavers. Each VMU was loaded at 3 Nm of torque sequentially in flexion, extension, and in right and left lateral bending. The range-of-motion (ROM) was measured with a Zebris 3D® system. The intervertebral disc cross-sectional area was measured on lateral and ventrodorsal radiographs. Biomechanical testing and radiographic measurements were performed with an intact disc, after disc fenestration, and after IVBS placement. Data were reported as mean ± SD.

Results: The intervertebral disc cross-sectional area was significantly decreased after disc fenestration and increased after IVBS placement, but remained significantly smaller than the area of intact disc in some of the tested conditions. The ROM with an intact disc, after disc fenestration and after IVBS placement, in flexion were 11.5° ± 1.0, 15.2° ± 2.3, and 10.9° ± 4.7, respectively, and in extension were 15.6° ± 3.7, 24.7° ± 6.2, 21.9° ± 4.0, respectively. There was a significant increase in extension ROM after disc fenestration. Intervertebral body spacer placement significantly decreased ROM in flexion but ROM in extension was not different from disc fenestration. No significant changes in lateral bending ROM were detected.

Clinical significance: The use of an IVBS reduced disc space collapse but did not restore stability of the VMU to normal values in extension after cervical disc fenestration.
Bevacizumab-Based Therapy for Colorectal Cancer: Experience from a Large Canadian Cohort at the Jewish General Hospital between 2004 and 2009
Authors: Bouganim N. , Mamo A. , Wasserman D.W. , Batist G. , Metrakos P. , Chaudhury P. , Hassanain M. , Kavan P.
Published: October 2013

Background: Before its regulatory approval in Canada, bevacizumab to treat patients with colorectal cancer (CRC) was accessed through the Bevacizumab Expanded Access Trial and a special-access program at the Jewish General Hospital. We retrospectively evaluated patient outcomes in that large cohort. Methods: All patients (n = 196) had metastatic CRC, were bevacizumab-naïve, and received bevacizumab in combination with chemotherapy at the Jewish General Hospital between 2004 and 2009. We collected patient demographics and clinical characteristics; relevant medical history, disease stage and tumour pathology at diagnosis; type, duration, and line of therapy; grades 3 and 4 adverse events (AES), time to disease progression (TTP), and overall survival (OS) from diagnosis. Results: Median follow-up was 36.0 months. Median TTP was 8.0 months [95% confidence interval (CI): 7.0 to 9.0 months). Median OS was 41.0 months (95% CI: 36.0 to 47.0 months). Of the 40 grades 3 and 4 bevacizumabrelated AES experienced by 38 patients (19.4%), the most common were thrombocytopenia (n = 17), deep-vein thrombosis (n = 6), pulmonary embolism (n = 4), and hypertension (n = 3). Conclusions: In an expanded access setting, our data reflect the efficacy and safety of bevacizumab-based therapy in the controlled post-registration clinical trial setting.
Should Noncurative Resection of the Primary Tumour Be Performed in Patients with Stage iv Colorectal Cancer? A Systematic Review and Meta-Analysis
Authors: Ahmed S. , Shahid R.K. , Leis A. , Haider K. , Kanthan S. , Reeder B. , Pahwa P.
Published: October 2013

Purpose: Surgical resection of the primary tumour in patients with advanced colorectal cancer (CRC) remains controversial. This review compares survival in patients with advanced crc who underwent surgical resection of the primary tumour with that in patients not undergoing resection, and determines rates of post-operative mortality and nonfatal complications, the primary tumour complication rate, the non-resection surgical procedures rate, and quality of life (QOL). Methods: Reports in the CENTRAL, MEDLINE, and EMBASE databases were searched for relevant studies, which were selected using pre-specified eligibility criteria. The search was also restricted to publication dates from 1980 onward, the English language, and studies involving human subjects. Screening, evaluation of relevant articles, and data abstraction were performed in duplicate, and agreement between the abstractors was assessed. Articles that met the inclusion criteria were assessed for quality using the Newcastle–Ottawa Scale. Data were collected and synthesized per protocol. Results: From among the 3379 reports located, fifteen retrospective observational studies were selected. Of the 12,416 patients in the selected studies, 8620 (69%) underwent surgery. Median survival was 15.2 months (range: 10–30.7 months) in the resection group and 11.4 months (range: 3–22 months) in the non-resection group. Hazard ratio for survival was 0.69 [95% confidence interval (CI): 0.61 to 0.79] favouring surgical resection. Mean rates of postoperative mortality and nonfatal complications were 4.9% (95% CI: 0% to 9.7%) and 25.9% (95% CI: 20.1% to 31.6%) respectively. The mean primary tumour complication rate was 29.7% (95% CI: 18.5% to 41.0%), and the non-resection surgical procedures rate in the non-resection group was 27.6% (95 CI: 15.4% to 39.9%). No study provided QOL data. Conclusions: Although this review supports primary tumour resection in advanced CRC, the results have significant biases. Randomized trials are warranted to confirm the findings.
Drug-Induced Subacute Cutaneous Lupus Erythematosus Associated with Nab-Paclitaxel Therapy
Authors: Lamond N.W.D. , Younis T. , Purdy K. , Dorreen M.S.
Published: October 2013

Drug-induced lupus erythematosus (DILE) syndromes are documented complications of chemotherapeutic agents, including paclitaxel. Subacute cutaneous lupus erythematosus (SCLE) is a distinct DILE syndrome presenting with characteristic annular or papulosquamous skin lesions in a photosensitive distribution with associated high anti-SSA titres. Previously, DILE syndromes complicating paclitaxel therapy have been attributed to polyethoxylated castor oil (Kolliphor EL: BASF, Ludwigshafen, Germany), the biologic solvent included in the drug’s original formulation (Taxol: Bristol–Myers Squibb, Montreal, QC), rather than the parent chemotherapy molecule. Here, we report a characteristic case of drug-induced SCLE complicating treatment with nanoparticle albumin bound (nab)–paclitaxel (Abraxane: Celgene, Summit, NJ, U.S.A.), a solvent-free taxane formulation. The pertinent English-language literature is also discussed. This case report is the first to link solvent-free paclitaxel with SCLE, and it suggests that the parent molecule is responsible for the reaction.
Assessment Integration in Serious Games
Authors: Hainey Thomas , Connolly Thomas M. , Chaudy Yaëlle , Boyle Elizabeth , Beeby Richard , Soflano Mario
Published: October 2013

Serious Games (SG) are developing a reputation with some educationalists as a useful supplementary approach for teaching and learning. Two important issues for SG application developers and educationalists are how the learning is assessed and how assessment is integrated into a SG application. This chapter presents the results of a systematic literature review on assessment integration in SG and highlights the state of the literature in this area by outlining important papers to act as a guide for educationalists tackling this important issue. This chapter defines assessment and discusses formative and summative assessment and embedded and external assessment. A discussion of traditional assessment approaches and assessment approaches in SG are presented along with a discussion of existing frameworks for the integration of assessment into a SG application. The chapter presents a number of examples of assessment in serious games.
CD8+ T Cell Responses to Lytic EBV Infection: Late Antigen Specificities as Subdominant Components of the Total Response
Authors: Abbott Rachel J. M. , Quinn Laura L. , Leese Alison M. , Scholes Harry M. , Pachnio Annette , Rickinson Alan B.
Published: October 2013

EBV elicits primary CD8+ T cell responses that, by T cell cloning from infectious mononucleosis (IM) patients, appear skewed toward immediate early (IE) and some early (E) lytic cycle proteins, with late (L) proteins rarely targeted. However, L Ag-specific responses have been detected regularly in polyclonal T cell cultures from long-term virus carriers. To resolve this apparent difference between responses to primary and persistent infection, 13 long-term carriers were screened in ex vivo IFN-γ ELISPOT assays using peptides spanning the two IE, six representative E, and seven representative L proteins. This revealed memory CD8 responses to 44 new lytic cycle epitopes that straddle all three protein classes but, in terms of both frequency and size, maintain the IE > E > L hierarchy of immunodominance. Having identified the HLA restriction of 10 (including 7 L) new epitopes using memory CD8+ T cell clones, we looked in HLA-matched IM patients and found such reactivities but typically at low levels, explaining why they had gone undetected in the original IM clonal screens. Wherever tested, all CD8+ T cell clones against these novel lytic cycle epitopes recognized lytically infected cells naturally expressing their target Ag. Surprisingly, however, clones against the most frequently recognized L Ag, the BNRF1 tegument protein, also recognized latently infected, growth-transformed cells. We infer that BNRF1 is also a latent Ag that could be targeted in T cell therapy of EBV-driven B-lymphoproliferative disease.
Geological reconnaissance, southern Baffin Island, district of Franklin
Authors: Blackadar R G
Published: October 2013

Operation Amadjuak, a helicopter-supported project, completed the geological reconnaissance of that part of Bafin Island that lies south of latitude G6" N and southwest of Cumberland Sound, an area. of about 50,000 square miles. Southern Baffin Island is composed
primarily of a wide variety of metamorphic rocks, which on the basis of the few currently available isotopic age determinations, are all part of the Churchill Structural Province. Palaeozoic carbonate and argillaceous carbonate rocks outcrop to the south and northwest of Amadjuak Lake. Several small
outliers including Silliman's Fossil Mount occur between the main outcrop area and Frobisher Bay. A Middle Ordovician age has tentatively been assigned to the Palaeozoic rocks
Evolution of cyclonic eddies and biogenic fluxes in the northern Bay of Bengal
Authors: Nuncio M. , Prasanna Kumar S.
Published: October 2013

Abstract. The Bay of Bengal has been traditionally known for its low primary productivity and varied reasons were attributed to it. The data analysis from the sediment traps deployed in the northern Bay of Bengal during the 5 yr from 1994 show episodic events of enhanced downward biogenic flux every year which was not related to monsoon-driven seasonal cycle. Satellite-derived sea level anomaly suggests that the episodic increase in the biogenic flux was associated with the presence of cyclonic eddies in the sediment trap location. Cyclonic eddy-induced down ward biogenic flux in the sediment trap location was larger than the amplitude, ∼40 mg m−2 d−1, of the seasonal cycle. The magnitude of the peak episodic fluxes were one-and-half to two-and-half times the annual mean flux, while the anomaly of peak episodic fluxes was at least equal to or greater than the magnitude of the seasonal flux value. Cyclonic eddies responsible for high biogenic flux during 1994 and 1996 were formed in the northern Bay of Bengal during February–March of respective years due to the interaction of northward flowing western boundary current and coastally trapped Kelvin wave. In contrast, cyclonic eddies during 1997 and 1998 were formed from the breaking of westward propagating Rossby waves. The sediment trap data provided the observational evidence that eddy-induced biological productivity is an important mechanism in the Bay of Bengal that contributes significantly to the mid-depth biogenic flux.
Effectiveness of acidizing geothermal wells in the South German Molasse Basin
Authors: Schumacher S. , Schulz R.
Published: October 2013

Abstract. In Germany, many hydro-geothermal plants have been constructed in recent years, primarily in the region of Munich. As the host formation here mainly consists of carbonates, nearly all recently drilled wells have been acidized in order to improve the well yield. In this study, the effectiveness of these acid treatments is analyzed with respect to the amount of acid used and the number of acid treatments carried out per well. The results show that the first acid treatment has the largest effect, while subsequent acidizing improves the well only marginally. Data also indicate that continued acidizing can lead to degradation of the well. These findings may not only be important for geothermal installations in Germany but also for projects, for example, in Austria, France or China where geothermal energy is produced from carbonate formations as well.
Spectral induced polarization measurements for predicting the hydraulic conductivity in sandy aquifers
Authors: Attwa M. , Günther T.
Published: October 2013

Abstract. Field and laboratory spectral induced polarization (SIP) measurements are integrated to characterize the hydrogeological conditions at the Schillerslage test site in Germany. The phase images are capable of monitoring thin peat layers within the sandy aquifers. However, the field results show limitations of decreasing resolution with depth. In comparison with the field inversion results, the SIP laboratory measurements show a certain shift in SIP response due to different compaction and sorting of the samples. The SIP data are analyzed to derive an empirical relationship for predicting the hydraulic conductivity (K). In particular, two significant but weak correlations between individual real resistivities (ρ') and relaxation times (τ), based on a Debye decomposition (DD) model, with measured K are found for the upper groundwater aquifer. The maximum relaxation time (τmax) and logarithmically weighted average relaxation time (τlw) show a better relation with K values than the median value τ50. A combined power law relation between individual ρ' and τ with K is developed with an expression of A · (ρ')B · (τlw)C, where A, B and C are determined using a least-squares fit between the measured and predicted K. The suggested approach with the calculated coefficients of the first aquifer is applied for the second. Results show good correlation with the measured K indicating that the derived relationship is superior to single phase angle models as Börner or Slater models.
Eddy length scales and the Rossby radius in the Arctic Ocean
Authors: Nurser A. J. G. , Bacon S.
Published: October 2013

Abstract. The first (and second) baroclinic deformation (or Rossby) radii are presented and discussed north of ~60° N, focusing on deep basins and shelf seas in the high Arctic Ocean, the Nordic Seas, Baffin Bay, Hudson Bay and the Canadian Arctic Archipelago, derived from high-resolution ice-ocean general circulation model output. Comparison of the model output with measured results shows that low values of the Rossby radius (in shallow water) and high values (in the Canada Basin) are accurately reproduced, while intermediate values (in the region of the Makarov and Amundsen Basins) are overestimated. In the high Arctic Ocean, the first Rossby radius increases from ~5 km in the Nansen Basin to ~15 km in the central Canadian Basin. In the shelf seas and elsewhere, values are low (1–7 km), reflecting weak density stratification, shallow water, or both. Seasonality only strongly impacts the Rossby radii in shallow seas where winter homogenisation of the water column can reduce it to the order of 100 m. We also offer an interpretation and explanation of the observed scales of Arctic Ocean eddies.
Ownership Transition: Ensuring a Successful Sale of Your Water Company
Authors: Maxwell Steve
Published: October 2013

A wave of consolidation activity has been sweeping over the water industry. This frenzy of investment, merger and acquisition activity has been a constant presence in this industry for about 15 years. Even though it always seems to be reaching new highs, investment interest in the water industry seems to continue to grow. The blockbuster deals that we read about in the news are mostly between the bigger players, but all of this activity doesn't go unnoticed by the thousands of smaller and mid‐sized companies that make up most of this industry.
The Loosening Role of Polyphony: Texture and Formal Functions in Mozart’s “Haydn” Quartets
Authors: Bakulina Olga Ellen
Published: October 2013

This essay demonstrates that texture can act as a form-defining factor by focusing on one specific textural type: imitative polyphony. Mozart’s six quartets dedicated to Haydn illustrate this claim. Building on William Caplin’s form-functional theory and his distinction between tight-knit and loose organization, imitative texture is shown to serve two purposes: as a loosening device, and as a means of textural and phrase-structural contrast. To deepen our understanding of polyphony’s formal and expressive roles, two new concepts are proposed:contrast pairandimitative presentation.The contrast-pair principle is then explored in select Viennese quartets by Mozart’s contemporaries.
The Theory and Practice of Integrating Invertible Counterpoint into Classical Theme-Types
Authors: Franck Peter
Published: October 2013

This essay investigates the use of invertible counterpoint within conventional theme-types encountered within Classical-style works. Whereas recent research has focused on how this contrapuntal technique provides a means of creating continuity, this article expands the purview by elucidating how it works in concert with theme-types, forms regulated by cadences (devices that arguably suppress continuity). A basic model provides the theoretical framework with which to analyze excerpts from a selection of works by Beethoven, Haydn, and Mozart. The analyses reveal that some theme-types are more successful than others at integrating invertible counterpoint into their formal design. Moreover, the analyses uncover the purpose of using invertible counterpoint within theme-types.
Production of Monoclonal Antibodies
Authors: Yokoyama Wayne M. , Christensen Michelle , Santos Gary Dos , Miller Diane , Ho Jason , Wu Tao , Dziegelewski Michael , Neethling Francisca A.
Published: October 2013

This unit describes the production of monoclonal antibodies beginning with immunization, cell fusion, and selection. Support protocols are provided for screening primary hybridoma supernatants for antibodies of desired specificity, establishment of stable hybridoma lines, cloning of these B cell lines by limiting dilution to obtain monoclonal lines, and preparation of cloning/expansion medium. An alternate protocol describes cell fusion and one‐step selection and cloning of hybridomas utilizing a semi‐solid methylcellulose‐based medium (ClonaCell‐HY from StemCell Technologies). Curr. Protoc. Immunol. 102:2.5.1‐2.5.29. © 2013 by John Wiley & Sons, Inc.
Superresolution Imaging with Standard Fluorescent Probes
Authors: Millis Bryan A. , Burnette Dylan T. , Lippincott‐Schwartz Jennifer , Kachar Bechara
Published: October 2013

For more than 100 years, the ultimate resolution of a light microscope (∼200 nm) has been constrained by the fundamental physical phenomenon of diffraction, as described by Ernst Abbe in 1873. While this limitation is just as applicable to today's light microscopes, it is the combination of high‐end optics, clever methods of sample illumination, and computational techniques that has enabled researchers to access information at an order of magnitude greater resolution than once thought possible. This combination, broadly termed superresolution microscopy, has been increasingly practical for many labs to implement from both a hardware and software standpoint, but, as with many cutting‐edge techniques, it also comes with limitations. One of the current drawbacks to superresolution microscopy is the limited number of probes and conditions that have been suitable for imaging. Here, a technique termed bleaching/blinking‐assisted localization microscopy (BaLM) makes use of the inherent blinking and bleaching properties of almost all fluorophores as a means to generate superresolution images. Curr. Protoc. Cell Biol. 60:21.8.1‐21.8.17. © 2013 by John Wiley & Sons, Inc.
On the Air With a Paleoclimatologist
Authors: Osborne Mike
Published: October 2013

The path of science news goes something like this: Nature is doing something interesting, scientist discovers the interesting thing, reporter talks to scientist, public hears reporter, public understands nature better, world is a better place. This is what I learned over the summer working as a science reporter at KQED public radio in San Francisco.
Moon‐based EUV imaging of the Earth's Plasmasphere: Model simulations
Authors: He Fei , Zhang Xiao‐Xin , Chen Bo , Fok Mei‐Ching , Zou Yong‐Liao
Published: October 2013

The EUV imager on board the Chang'E‐3 lunar lander will image the Earth's plasmasphere from a lunar perspective to focus on some of the open questions in plasmaspheric researches (i.e., global structures, erosion, and refilling of plasmasphere). In order to achieve the understanding of the plasmaspheric dynamics in relation to these EUV images in lunar perspective, the He+ 30.4 nm emission intensities and global structures of the plasmasphere viewed from the moon are investigated using a dynamic global core plasma model embedded with TS07 magnetic field model and W05 electric field model. Two typical storms observed by the IMAGE EUV imager are systematically simulated from the perspectives of the moon. It is found from the simulations that the maximum emission intensity of the plasmasphere is ~12.3 R which is greater than that detected from polar orbit, and the global shapes and temporal evolutions of large‐scale plasmaspheric structures (plasmapause, shoulder, and plume) also have different patterns in moon‐based simulated images. It is also shown that the plasmaspheric structures extracted from moon‐based EUV images are in agreement with those from IMAGE EUV images. Systematic simulations demonstrate that specific latitudinal distribution of the plasmaspheric structures can only be imaged at specific positions in lunar orbit. It is expected that this investigation provides us with an overall understanding on moon‐based EUV images and helps to identify the plasmaspheric structures and evolution patterns in future moon‐based EUV imaging.
A comparison of the effects of initializing different thermosphere‐ionosphere model fields on storm time plasma density forecasts
Authors: Chartier Alex T. , Jackson David R. , Mitchell Cathryn N.
Published: October 2013

Data assimilation has been used successfully for real‐time ionospheric specification, but it has not yet proved advantageous for forecasting. The most challenging and important ionospheric events to forecast are storms. The work presented here examines the effectiveness of data assimilation in a storm situation, where the initial conditions are known and the model is considered to be correct but the external solar and geomagnetic drivers are poorly specified. The aim is to determine whether data assimilation could be used to improve storm time forecast accuracy. The results show that, in the case of the storm of Halloween 2003, changes made to the model's initial thermospheric conditions improve electron density forecasts by at least 10% for 18 h, while changes to ionospheric fields alone result in >10% forecast accuracy improvement for less than 4 h. Further examination shows that the neutral composition is especially important to the accuracy of ionospheric electron density forecasts. Updating the neutral composition gives almost all the benefits of updating the complete thermospheric state. A comparison with real, globally distributed observations of vertical total electron content confirms that updating the thermospheric composition can improve forecast accuracy.
Modeling energetic electron penetration into the slot region and inner radiation belt
Authors: Zhao H. , Li X.
Published: October 2013

The inner radiation belt is thought to be quite stable, and only the most intense geomagnetic storms can cause energetic electron variations in the slot region and inner belt. In this paper, using energetic electron flux data from Detection of Electro‐Magnetic Emissions Transmitted from Earthquake Regions (DEMETER) satellite, we show that 100s keV electron flux enhancements in the slot region and inner belt are seen quite often and can occur even during moderate geomagnetic storms. In addition, by transforming the energetic electron flux data into the phase space density (PSD), we model the inward radial transport of two different electron populations, μ=30 MeV/G (K=0) and μ=15 MeV/G (K=0), using a 1‐D radial diffusion model in which the radial diffusion coefficient is directly associated with solar wind parameters and L shell. The model results reproduce the PSD data well in the slot region and inner belt, indicating that the flux enhancement in the inner belt and slot region can be well explained by inward radial transport. The radial diffusion coefficients used in our model are much larger than the widely used Kp‐dependent electromagnetic radial diffusion coefficient but are smaller than the Kp‐dependent electrostatic radial diffusion coefficient (Brautigam and Albert, 2000), suggesting that the Kp‐dependent diffusion coefficient cannot be simply extended to lower L region to account for the observed enhancements of energetic electrons in the slot region and inner belt.
Current structures associated with dipolarization fronts
Authors: Yao Zhonghua , Sun W. J. , Fu S. Y. , Pu Z. Y. , Liu Jiang , Angelopoulos V. , Zhang X.‐J. , Chu X. N. , Shi Q. Q. , Guo R. L. , Zong Q.‐G.
Published: October 2013

Recently, observational results on currents around the dipolarization fronts (DFs) of earthward flow bursts have attracted much research attention. These currents are found to have close association with substorm intensifications. This paper devotes to further study of the current system ahead and within the DFs with high‐resolution magnetic field measurements from Cluster constellation in 2003. The separation of four spacecraft is much smaller than the scales of spatial structures ahead and within the DF layer so that the currents can be reliably obtained. Based on features of the magnetic field variations prior to the fronts, we categorized the DFs into two types: DFs with magnetic dips immediate ahead of the fronts (type I) and DFs without magnetic dips (type II). For type I DFs, it is found that dawnward currents along the DFs exist in the dip region; duskward currents exist within the fronts. Furthermore, the dawnward currents in the dip region are found to be mainly parallel to the local magnetic field with a spatial scale of ~1000 km, whereas the duskward currents within the fronts have both significant parallel and perpendicular components. On the other hand, for type II DFs, only significant duskward and mainly perpendicular currents show up within the fronts; no dawnward currents exist ahead of DFs. The dawnward and mainly parallel current in the type I DFs is important in the current coupling process between magnetosphere and ionosphere and may lead to local current disruptions for substorm initiations.
Temperature dynamics during nonisothermal evaporation from drying porous surfaces
Authors: Aminzadeh M. , Or D.
Published: October 2013

Key Points

Analytical quantification of evaporation rate and surface temperature coupling

Offering a physical basis for interpreting empirical remote sensing methods

Quantifying the difference between isothermal and non‐isothermal evaporation
Genetic Manipulation of Streptococcus pyogenes (The Group A Streptococcus, GAS)
Authors: Le Breton Yoann , McIver Kevin S.
Published: October 2013

Streptococcus pyogenes (the Group A Streptococcus, GAS) is a Gram‐positive bacterium responsible for a wide spectrum of diseases ranging from mild superficial infections (pharyngitis, impetigo) to severe, often life‐threatening invasive diseases (necrotizing fasciitis, streptococcal toxic shock syndrome) in humans. This unit describes molecular techniques for the genetic manipulation of S. pyogenes with detailed protocols for transformation, gene disruption, allelic exchange, transposon mutagenesis, and genetic complementation. Curr. Protoc. Microbiol. 30:9D.3.1‐9D.3.29. © 2013 by John Wiley & Sons, Inc.
Addition of amino acid moieties to lapatinib increases the anti‐cancer effect via amino acid transporters
Authors: Maeng Han‐Joo , Kim Eun‐Seo , Chough Chieyeon , Joung Misuk , Lim Jee Woong , Shim Chang‐Koo , Shim Won‐Sik
Published: October 2013

Anti‐cancer agents delivered to cancer cells often show multi‐drug resistance (MDR) due to expulsion of the agents. One way to address this problem is to increase the accumulation of anti‐cancer agents in cells via amino acid transporters. Thus, val‐lapatinib and tyr‐lapatinib were newly synthesized by adding valine and tyrosine moieties, respectively, to the parent anti‐cancer agent lapatinib without stability issues in rat plasma. Val‐lapatinib and tyr‐lapatinib showed enhanced anti‐cancer effects versus the parent lapatinib in various cancer cell lines, including human breast cancer cells (MDA‐MB‐231, MCF7) and lung cancer cells (A549), but not in non‐cancerous MDCK‐II cells. A glutamine uptake study revealed that both val‐lapatinib and tyr‐lapatinib, but not the parent lapatinib, inhibited glutamine transport in MDA‐MB‐231 and MCF7 cells, suggesting the involvement of amino acid transporters. In conclusion, val‐lapatinib and tyr‐lapatinib have enhanced anti‐cancer effects, likely due to an increased uptake of the agents into cancer cells via amino acid transporters. The present data suggest that amino acid transporters may be an effective drug delivery target to increase the uptake of anti‐cancer agents, leading to one method of overcoming MDR in cancer cells. Copyright © 2013 John Wiley & Sons, Ltd.
Iterative Antimicrobial Candidate Selection from Informed D‐/L‐Peptide Dimer Libraries
Authors: Lichtenecker Roman J. , Ellinger Bernhard , Han Hong‐Mei , Jadhav Kirtikumar B. , Baumann Sascha , Makarewicz Oliwia , Grabenbauer Markus , Arndt Hans‐Dieter
Published: October 2013

Growing resistance to antibiotics, as well as newly emerging pathogens, stimulate the investigation of antimicrobial peptides (AMPs) as therapeutic agents. Here, we report a new library design concept based on a stochastic distribution of natural AMP amino acid sequences onto half‐length synthetic peptides. For these compounds, a non‐natural motif of alternating D‐ and L‐backbone stereochemistry of the peptide chain predisposed for β‐helix formation was explored. Synthetic D‐/L‐peptides with permuted half‐length sequences were delineated from a full‐length starter sequence and covalently recombined to create two‐dimensional compound arrays for antibacterial screening. Using the natural AMP magainin as a seed sequence, we identified and iteratively optimized hit compounds showing high antimicrobial activity against Gram‐positive and Gram‐negative bacteria with low hemolytic activity. Cryo‐electron microscopy characterized the membrane‐associated mechanism of action of the new D‐/L‐peptide antibiotics.
CO2 Complexation and Activation by a Trost‐Bis(ProPhenol)Cobalt Complex
Authors: Netto Caterina G. C. M. , Toma Henrique E.
Published: October 2013

A binuclear cobalt complex, [Co2BPP], derived from the (R,R)‐Trost‐bis‐ProPhenol (BPP) ligand, has been investigated as a catalyst for CO2 uptake and its electrochemical reduction. The complex exhibits labile acetate ligands that can be readily exchanged with CO2, leading to pronounced changes in its vibrational spectra, with νC=O peaks observed at 1700 and 1596 cm–1. The electrochemical reduction of the CoIII centers at –0.5 V was significantly enhanced in the presence of CO2, evidencing a chemical reaction coupled to an electrode process. Instead of yielding CO or HCOOH as observed in most artificial systems, formaldehyde was identified as the major product below –1.0 V, showing that CO2 can undergo four‐electron reduction by the [Co2BPP] electrocatalyst.
The effect of ethylene oxide sterilization on the surface chemistry and in vitro cytotoxicity of several kinds of chitosan
Authors: França Rodrigo , Mbeh Doris A. , Samani Taraneh Djavanbakht , Le Tien Canh , Mateescu Mircea A. , Yahia L'Hocine , Sacher Edward
Published: October 2013

The surfaces of three chitosan samples, differing only in their degrees of deacetylation and of carboxyethyl chitosan were chemically characterized by X‐ray photoelectron spectroscopy, time‐of‐flight secondary ion mass spectroscopy, X‐ray diffraction, and Fourier transform infrared, both before and after sterilization with ethylene oxide. Unexpected elemental ratios suggest that surface chemical modification occurred during the processing of the original chitin, with further surface modification on subsequent sterilization, despite previous reports to the contrary. Cell viability was evaluated by direct contact methyl thiazole tetrazolium and lactate dehydrogenase assays between the chitosan particles and A549 human epithelial cells, which demonstrated that the modifications incurred on sterilization are reflected in biocompatibility changes. All the samples were found to be biocompatible and nontoxic before sterilization and remained so subsequently. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 101B: 1444–1455, 2013.
Picomole‐level Formaldehyde Determination in Gaseous and Beer Samples Using Flow Injection Chemiluminescence Analysis
Authors: Tan Xijuan , Song Zhenghua
Published: October 2013

Based on the linear enhancement of formaldehyde (FA) within 7.0 ∼ 1000 pmol l−1 on luminol—bovine serum albumin (BSA) chemiluminescence (CL) system, FA determination in air and beer samples using CL with flow injection (FI) was proposed. The detection limit was 2.5 pmol l−1 (3σ) and the relative standard deviations were less than 4.5% (n = 7). At a flow rate of 2.0 mL min−1, a whole analysis from sampling to washing only needed 32 s, offering a sample throughput of 112 h−1. This proposed method was successfully utilized to determine FA vapor pressure in liquid (121.8 ± 3.8 Pa), FA content in real air sample (8.93 ± 0.03 mg m−3), and FA levels in beer (199.5 ± 5.6 ∼ 225.2 ± 3.5 mg l−1), giving determination recoveries from 90.7% to 109.3%. The mechanism of BSA—FA interaction was also investigated, showing FA binding to BSA was a spontaneous process mainly through hydrogen bonding and van der Waals force by FI‐CL, with binding constant K of 1.89 × 106 l mol−1 and the number of binding sites n of 0.86. Molecular docking analysis further revealed FA could enter into the pocket at subdomain IIA of BSA, with K of 1.71 × 105 l mol−1 and ΔG of ‐29.68 kJ mol−1.
Is the thrombus truly free‐floating? A case report
Authors: Demir Kenan , Avci Ahmet , Altunkeser Bulent Behlul , Ugras Nevzat Serdar
Published: October 2013

A free‐floating thrombus in the left atrium is very rare in mitral stenosis. Such a thrombus can lead to sudden circulatory arrest and syncope or can cause severe cerebral or peripheral thromboembolic events. Clinical diagnosis is difficult, but left atrial thrombus should be suspected if patients with mitral stenosis and atrial fibrillation have intermittent or changing murmurs, emboli, or syncope. We describe the case of a patient with mild mitral stenosis under warfarin therapy, and a left atrial pedunculated thrombus discovered during the investigation for syncope attacks. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound 42:252–255, 2014
Longitudinal changes in MRI markers in a reversible unilateral ureteral obstruction mouse model: Preliminary experience
Authors: Haque Muhammad E. , Franklin Tammy , Bokhary Ujala , Mathew Liby , Hack Bradley K. , Chang Anthony , Puri Tipu S. , Prasad Pottumarthi V.
Published: October 2013

Purpose

To evaluate longitudinal changes in renal oxygenation and diffusion measurements in a model of reversible unilateral ureteral obstruction (rUUO) which has been shown to induce chronic renal functional deficits in a strain dependent way. C57BL/6 mice show higher degree of functional deficit compared with BALB/c mice. Because hypoxia and development of fibrosis are associated with chronic kidney diseases and are responsible for progression, we hypothesized that MRI measurements would be able to monitor the longitudinal changes in this model and will show strain dependent differences in response. Here blood oxygenation level dependent (BOLD) and diffusion MRI measurements were performed at three time points over a 30 day period in mice with rUUO.

Materials and Methods

The studies were performed on a 4.7T scanner with the mice anesthetized with isoflurane before UUO, 2 and 28 days postrelease of 6 days of obstruction.

Results

We found at the early time point (∼2 days after releasing the obstruction), the relative oxygenation in C57Bl/6 mice were lower compared with BALB/c. Diffusion measurements were lower at this time point and reached statistical significance in BALB/c

Conclusion

These methods may prove valuable in better understanding the natural progression of kidney diseases and in evaluating novel interventions to limit progression. J. Magn. Reson. Imaging 2014;39:835–841. © 2013 Wiley Periodicals, Inc.
Temperature‐Induced Formation of Polymeric Nanoparticles: In Situ SAXS and QENS Experiments
Authors: Sedlak Marian , Falus Peter , Steinhart Milos , Gummel Jeremie , Stepanek Petr , Filippov Sergey K.
Published: October 2013

Early stages of polymeric nanoparticle formation are monitored by in situ synchrotron small‐angle X‐ray scattering (SAXS) experiments. A new strategy enables the preparation of stable polymeric nanoparticles from homopolymers (not copolymers) of one type only and without any assembly‐triggering additives. Poly(ethylacrylic acid) (PEA) in an aqueous solution is tuned to the pH, where it exhibits thermosensitivity and the formation of nanoparticles is temperature‐induced. The kinetics of this formation are clearly monitored by SAXS. Experiments indicate the slightly elongated, not exactly spherical shape of the resulting nanoparticles, which is also confirmed by cryo‐transmission electron microscopy (cryo‐TEM). Quasielastic neutron scattering (QENS) shows that the PEA nanoparticles are relatively loose with a lot of solvent inside, in agreement with results from previous light scattering work.

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Feasibility of semiautomated MR volumetry using gadoxetic acid–enhanced MRI at hepatobiliary phase for living liver donors
Authors: Lee Jeongjin , Kim Kyoung Won , Kim So Yeon , Kim Bohyoung , Lee So Jung , Kim Hyoung Jung , Lee Jong Seok , Lee Moon Gyu , Song Gi‐Won , Hwang Shin , Lee Sung‐Gyu
Published: October 2013

Purpose

To assess the feasibility of semiautomated MR volumetry using gadoxetic acid–enhanced MRI at the hepatobiliary phase compared with manual CT volumetry.

Methods

Forty potential live liver donor candidates who underwent MR and CT on the same day, were included in our study. Semiautomated MR volumetry was performed using gadoxetic acid–enhanced MRI at the hepatobiliary phase. We performed the quadratic MR image division for correction of the bias field inhomogeneity. With manual CT volumetry as the reference standard, we calculated the average volume measurement error of the semiautomated MR volumetry. We also calculated the mean of the number and time of the manual editing, edited volume, and total processing time.

Results

The average volume measurement errors of the semiautomated MR volumetry were 2.35% ± 1.22%. The average values of the numbers of editing, operation times of manual editing, edited volumes, and total processing time for the semiautomated MR volumetry were 1.9 ± 0.6, 8.1 ± 2.7 s, 12.4 ± 8.8 mL, and 11.7 ± 2.9 s, respectively.

Conclusion

Semiautomated liver MR volumetry using hepatobiliary phase gadoxetic acid–enhanced MRI with the quadratic MR image division is a reliable, easy, and fast tool to measure liver volume in potential living liver donors. Magn Reson Med 72:640–645, 2014. © 2013 Wiley Periodicals, Inc.
Temperature effects on the hydrodynamic radius of the intrinsically disordered N‐terminal region of the p53 protein
Authors: Langridge Timothy D. , Tarver Micheal J. , Whitten Steven T.
Published: October 2013

Intrinsically disordered proteins (IDPs) are often characterized in terms of the hydrodynamic radius, Rh. The Rh of IDPs are known to depend on fractional proline content and net charge, where increased numbers of proline residues and increased net charge cause larger Rh. Though sequence and charge effects on the Rh of IDPs have been studied, the temperature sensitivity has been noted only briefly. Reported here are Rh measurements in the temperature range of 5–75°C for the intrinsically disordered N‐terminal region of the p53 protein, p53(1–93). Of note, the Rh of this protein fragment was highly sensitive to temperature, decreasing from 35 Å at 5°C to 26 Å at 75°C. Computer generated simulations of conformationally dynamic and disordered polypeptide chains were performed to provide a hypothesis for the heat‐induced compaction of p53(1–93) structure, which was opposite to the heat‐induced increase in Rh observed for a model folded protein. The simulations demonstrated that heat caused Rh to trend toward statistical coil values for both proteins, indicating that the effects of heat on p53(1–93) structure could be interpreted as thermal denaturation. The simulation data also predicted that proline content contributed minimally to the native Rh of p53(1–93), which was confirmed by measuring Rh for a substitution variant that had all 22 proline residues changed for glycine. Proteins 2014; 82:668–678. © 2013 Wiley Periodicals, Inc.
Ultrathin Shell Double Emulsion Templated Giant Unilamellar Lipid Vesicles with Controlled Microdomain Formation
Authors: Arriaga Laura R. , Datta Sujit S. , Kim Shin‐Hyun , Amstad Esther , Kodger Thomas E. , Monroy Francisco , Weitz David A.
Published: October 2013

A microfluidic approach is reported for the high‐throughput, continuous production of giant unilamellar vesicles (GUVs) using water‐in‐oil‐in‐water double emulsion drops as templates. Importantly, these emulsion drops have ultrathin shells; this minimizes the amount of residual solvent that remains trapped within the GUV membrane, overcoming a major limitation of typical microfluidic approaches for GUV fabrication. This approach enables the formation of microdomains, characterized by different lipid compositions and structures within the GUV membranes. This work therefore demonstrates a straightforward and versatile approach to GUV fabrication with precise control over the GUV size, lipid composition and the formation of microdomains within the GUV membrane.
Influence of Individual Phospholipids on the Physical Properties of Oil‐Based Suspensions
Authors: Arnold G. , Schade E. , Schneider Y. , Friedrichs J. , Babick F. , Werner C. , Rohm H.
Published: October 2013

The impact of soybean lecithin and three individual phospholipids at different concentration (CPL) on rheology and sedimentation behavior of sugar/soybean oil suspensions (ϕ = 0.31) was studied and compared with attraction and retraction forces between sugar surfaces in soybean oil as measured by atomic force microscopy (AFM). In general, a surfactant‐induced reduction of yield stress, apparent viscosity and sediment volume of the suspensions coincides with a decrease of adhesive interactions between sugar particles in soybean oil. Although the general influence of individual phospholipids and soybean lecithin is comparable, it is concluded from investigations at low CPL that individual phospholipids exhibit a less pronounced impact on the analyzed parameters. Furthermore, at low CPL, binary mixtures of the phospholipids are more efficient than individual phospholipids as regards the reduction of yield stress and sediment volume. While the same tendency was detectable for AFM results, these differences were not statistically verified. Slight differences were also evident when comparing individual phospholipids and their influence on rheology and sedimentation which are, however, not in line with the results of AFM. A general understanding of these interrelations between surfactant composition and possible synergistic or antagonistic effects in mixtures of individual phospholipids contributes to optimizing lecithin composition with respect to functionality.
In vitro and in vivo study of dolichyl phosphate on the efflux activity of P‐glycoprotein at the blood–brain barrier
Authors: Ji Bian‐Sheng , Cen Juan , Liu Lu , He Ling
Published: October 2013

It has been commonly recognized that accumulated amyloid‐β (Aβ) in the brain plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Since the deficiency of the P‐glycoprotein (P‐gp) at the blood–brain barrier (BBB) in AD may aggravate Aβ deposition and the P‐gp reversal agents display lower selectivity of the action, to selectively restore activity of the efflux pump is eagerly required. This study was designed to investigate the influence of dolichyl‐phosphate (dolichyl‐P) on the P‐gp at the BBB. The results revealed that treatment with dolichyl‐P increased transendothelial transfer of Rhodamine123 (Rh123) and Aβ42 from the apical compartment to the basolateral compartment but reduced that from the basolateral compartment to the apical compartment in the co‐culture of rat brain microvessel endothelial cells (rBMECs) and astrocytes, down regulated P‐gp expression in rBMECs and significantly elevated content of Rh123 in rat cortex and hippocampus tissues. The present results implied that accumulated dolichyl‐P in the brain may exert an important role in the depression of the P‐gp at the BBB, which may suggest valuable clues to promote function of the pump at the BBB in AD.
Constraints on the age of the Great Sand Dunes, Colorado, from subsurface stratigraphy and OSL dates
Authors: Madole Richard F. , Mahan Shannon A. , Romig Joe H. , Havens Jeremy C.
Published: October 2013

The age of the Great Sand Dunes has been debated for nearly 150 yr. Seven ages ranging from Miocene to late Holocene have been proposed for them. This paper presents new information–chiefly subsurface stratigraphic data, OSL dates, and geomorphic evidence–that indicates that the Great Sand Dunes began to form in the latter part of the middle Pleistocene. The dunes overlie a thick wedge of piedmont-slope deposits, which in turn overlies sediment of Lake Alamosa, a paleolake that began to drain about 440 ka. The wedge of piedmont-slope deposits extends westward for at least 23 km and is as much as 60 m thick at a distance of 10 km from the Sangre de Cristo Range. Ostracodes from one well indicate that the eastern shoreline of Lake Alamosa extended to within 4.3 km of where the Great Sand Dunes eventually formed. The time represented by the wedge of piedmont-slope deposits is not known exactly, but the wedge post-dates 440 ka and was in place prior to 130 ka because by then the dunes overlying it were sufficiently close and tall enough to obstruct streams draining from the Sangre de Cristo Range.