bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface immobilization and bioactivity of TGF‐β1 inhibitor peptides for bone implant applications
Authors: Sevilla Pablo , Vining Kyle V. , Dotor Javier , Rodriguez Daniel , Gil F. Javier , Aparicio Conrado
Published: March 2015

TGF‐β1 is the most related cytokine with the production of fibrotic tissue. It plays an important role on the production of collagen by fibroblasts and other types of cells. The inhibition of this cytokine reduces fibrosis in various types of tissue. Biofunctionalization of dental and orthopedic implants with biomolecules enables modification of the physical, chemical and biochemical properties of their surfaces to improve its biological and clinical performance. Our objective was to develop a reliable method to immobilize oligopeptides on Ti surfaces to obtain a surface with TGF‐β1 inhibitory activity that will potentially minimize fibrotic encapsulation of implants during the process of osseointegration. We covalently immobilized TGF‐β1 inhibitor P17‐peptides on Ti surfaces and assessed by characterizing each step of the process that we successfully biofunctionalized the implant surfaces. High amounts of peptides were anchored and homogeneously distributed on the surfaces with mechanical and thermochemical stability after in vitro simulated challenges. Notably, the immobilized peptides retained their TGF‐β1 inhibitory activity in vitro. Thus, these biofunctional coatings are potential candidates for inducing a fast and reliable osseointegration in vivo. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 385–394, 2016.
New Insights In Intestinal Sar1B GTPase Regulation and Role in Cholesterol Homeostasis
Authors: Sané Alain , Seidman Ernest , Spahis Schohraya , Lamantia Valérie , Garofalo Carole , Montoudis Alain , Marcil Valérie , Levy Emile
Published: March 2015

Sar1B GTPase is a key component of Coat protein complex II (COPII)‐coated vesicles that bud from the endoplasmic reticulum to export newly synthesized proteins. The aims of this study were to determine whether Sar1B responds to lipid regulation and to evaluate its role in cholesterol (CHOL) homeostasis. The influence of lipids on Sar1B protein expression was analyzed in Caco‐2/15 cells by Western blot. Our results showed that the presence of CHOL (200 μM) and oleic acid (0.5 mM), bound to albumin, increases Sar1B protein expression. Similarly, supplementation of the medium with micelles composed of taurocholate with monooleylglycerol or oleic acid also stimulated Sar1B expression, but the addition of CHOL (200 μM) to micelle content did not modify its regulation. On the other hand, overexpression of Sar1B impacted on CHOL transport and metabolism in view of the reduced cellular CHOL content along with elevated secretion when incubated with oleic acid‐containing micelles for 24 h, thereby disclosing induced CHOL transport. This was accompanied with higher secretion of free‐ and esterified‐CHOL within chylomicrons, which was not the case when oleic acid was replaced with monooleylglycerol or when albumin‐bound CHOL was given alone. The aforementioned cellular CHOL depletion was accompanied with a low phosphorylated/non phosphorylated HMG‐CoA reductase ratio, indicating elevated enzymatic activity. Combination of Sar1B overexpression with micelle incubation led to reduction in intestinal CHOL transporters (NPC1L1, SR‐BI) and metabolic regulators (PCSK9 and LDLR). The present work showed that Sar1B is regulated in a time‐ and concentration‐dependent manner by dietary lipids, suggesting an adaptation to alimentary lipid flux. Our data also suggest that Sar1B overexpression contributes to regulation of CHOL transport and metabolism by facilitating rapid uptake and transport of CHOL. J. Cell. Biochem. 116: 2270–2282, 2015. © 2015 Wiley Periodicals, Inc.
Impairment of the Vascular KATP Channel Imposes Fatal Susceptibility to Experimental Diabetes Due to Multi‐Organ Injuries
Authors: Li Shan‐Shan , Cui Ningren , Yang Yang , Trower Timothy C. , Wei Yu‐Min , Wu Yang , Zhang Shuang , Jin Xin , Jiang Chun
Published: March 2015

The vascular isoform of ATP‐sensitive K+ (KATP) channels regulates blood flow to all organs. The KATP channel is strongly inhibited by reactive oxygen and carbonyl species produced in diabetic tissue inflammation. To address how such channel inhibition impacts vascular regulation as well as tissue viability, we performed studies in experimental diabetic mice. Strikingly, we found that knockout of the Kcnj8 encoding Kir6.1 subunit (Kcnj8‐KO) caused mice to be fatally susceptible to diabetes. Organ perfusion studies suggested that the lack of this vascular K+ channel handicapped activity‐dependent vasodilation, leading to hypoperfusion, tissue hypoxia, and multi‐organ failure. Morphologically, Kcnj8‐KO mice showed greater inflammatory cell infiltration, higher levels of expression of inflammation indicator proteins, more severe cell apoptosis, and worse tissue disruptions. These were observed in the kidney, liver, and heart under diabetic condition in parallel comparison to tissues from WT mice. Patch clamping and molecular studies showed that the KATP channel was S‐glutathionylated in experimental diabetes contributing to the inhibition of channel activity as well as the reduced arterial responses to vasodilators. These results suggest that the vascular KATP channel is organ protective in diabetic condition, and since the channel is suppressed by diabetic oxidative stress, therapeutical interventions to the maintenance of functional KATP channels may help to lower or prevent diabetic organ dysfunction. J. Cell. Physiol. 230: 2915–2926, 2015. © 2015 Wiley Periodicals, Inc.
Separation of the acid‐sugar mixtures by using acid retardation and further concentration of the eluents by using continuous‐effect membrane distillation
Authors: Liu Jianjun , Qin Yingjie , Li Pingli , Zhang Kunming , Liu Qing , Liu Liqiang
Published: March 2015

BACKGROUND

A major cost in acid‐catalysed hydrolysis of biomass to fermentable sugars is the consumption of acid itself. In this study, a combined process was developed in which the acid and sugar in the hydrolysate were separated using an acid retardation process and then the dilute aqueous product streams were concentrated using a continuous‐effect membrane distillation (CEMD) process, thus acid could be reused as catalyst.

RESULTS

The recovery rate of sugar was as high as 94.3–99.2% while the recovery rate of sulfuric acid was 92.4–98.9%. The eluents were further concentrated using the CEMD process. When a solution of 2 wt% sulfuric acid was concentrated to c. 40 wt%, the maximum value of permeation flux (Jw) and gained output ratio (GOR) was 6.20 L m−2 h−1 and 15.50, respectively. Meanwhile, the dilute aqueous sugar solution obtained from corn stover was concentrated 20‐fold to a final concentration of c. 497.6 g L−1 using the CEMD process with a final GOR of 5.5.

CONCLUSION

The combination of acid retardation and CEMD is suitable for the production of sugar, further purification and concentration of eluents; the sugar solution can be used for fermentation and acid solution can be reused as catalyst. © 2015 Society of Chemical Industry
Nutrient removal from biogas slurry and biogas upgrading of crude biogas at high CO2 concentrations using marine microalgae
Authors: Zhao Yongjun , Ge Zhigang , Zhang Hui , Bao Jiqing , Sun Shiqing
Published: March 2015

BACKGROUND

This study aims to simultaneously reduce biogas slurry nutrient and upgrade biogas via microalgal production. Marine microalgae were grown in a culture medium containing a mixture of seawater and biogas slurry with CO2 from synthetic biogas. The effects of different ratios of biogas slurry and various influent concentrations of CH4 in synthetic biogas on the growth of Nannochloropsis sp. were examined. Nutrient removal and biogas upgrading were also studied under different influent CH4 concentrations.

RESULTS

Nannochloropsis sp. showed optimal growth in 40% biogas slurry and significantly enhanced growth in synthetic biogas with 50% CO2. The optimal range of influent CH4 concentration for the removal of biogas slurry nutrients was 45% to 50%. Notably, the influent CH4 concentration of 60% (v/v) provided an optimal CO2 concentration for Nannochloropsis sp. cultivation. Advantageous CO2 removal and biogas upgrading were observed under this condition. This treatment increased CH4 concentration in synthetic biogas from 60% to 93.58% after 6 days cultivation.

CONCLUSION

Appropriate control of the biogas slurry or seawater and CH4 concentrations in the influent is crucial to simultaneously optimize nutrient removal and biogas upgrading. © 2015 Society of Chemical Industry
Histology of the heterostracan dermal skeleton: Insight into the origin of the vertebrate mineralised skeleton
Authors: Keating Joseph N. , Marquart Chloe L. , Donoghue Philip C. J.
Published: March 2015

Living vertebrates are divided into those that possess a fully formed and fully mineralised skeleton (gnathostomes) versus those that possess only unmineralised cartilaginous rudiments (cyclostomes). As such, extinct phylogenetic intermediates of these living lineages afford unique insights into the evolutionary assembly of the vertebrate mineralised skeleton and its canonical tissue types. Extinct jawless and jawed fishes assigned to the gnathostome stem evidence the piecemeal assembly of skeletal systems, revealing that the dermal skeleton is the earliest manifestation of a homologous mineralised skeleton. Yet the nature of the primitive dermal skeleton, itself, is poorly understood. This is principally because previous histological studies of early vertebrates lacked a phylogenetic framework required to derive evolutionary hypotheses. Nowhere is this more apparent than within Heterostraci, a diverse clade of primitive jawless vertebrates. To this end, we surveyed the dermal skeletal histology of heterostracans, inferred the plesiomorphic heterostracan skeleton and, through histological comparison to other skeletonising vertebrate clades, deduced the ancestral nature of the vertebrate dermal skeleton. Heterostracans primitively possess a four‐layered skeleton, comprising a superficial layer of odontodes composed of dentine and enameloid; a compact layer of acellular parallel‐fibred bone containing a network of vascular canals that supply the pulp canals (L1); a trabecular layer consisting of intersecting radial walls composed of acellular parallel‐fibred bone, showing osteon‐like development (L2); and a basal layer of isopedin (L3). A three layered skeleton, equivalent to the superficial layer L2 and L3 and composed of enameloid, dentine and acellular bone, is possessed by the ancestor of heterostracans + jawed vertebrates. We conclude that an osteogenic component is plesiomorphic with respect to the vertebrate dermal skeleton. Consequently, we interpret the dermal skeleton of denticles in chondrichthyans and jawless thelodonts as independently and secondarily simplified. J. Morphol. 276:657–680, 2015. © 2015 The Authors Journal of Morphology Published by Wiley Periodicals, Inc.
In vivo measurement reproducibility of femoral neck microarchitectural parameters derived from 3T MR images
Authors: Hotca Alexandra , Rajapakse Chamith S. , Cheng Chen , Honig Stephen , Egol Kenneth , Regatte Ravinder R. , Saha Punam K. , Chang Gregory
Published: March 2015

Purpose

To evaluate the within‐day and between‐day measurement reproducibility of in vivo 3D MRI assessment of trabecular bone microarchitecture of the proximal femur.

Materials and Methods

This Health Insurance Portability and Accountability Act (HIPPA)‐compliant, Institutional Review Board (IRB)‐approved study was conducted on 11 healthy subjects (mean age = 57.4 ± 14.1 years) with written informed consent. All subjects underwent a 3T MRI hip scan in vivo (0.234 × 0.234 × 1.5 mm) at three timepoints: baseline, second scan same day (intrascan), and third scan 1 week later (interscan). We applied digital topological analysis and volumetric topological analysis to compute the following microarchitectural parameters within the femoral neck: total bone volume, bone volume fraction, markers of trabecular number (skeleton density), connectivity (junctions), plate‐like structure (surfaces), plate width, and trabecular thickness. Reproducibility was assessed using root‐mean‐square coefficient of variation (RMS‐CV) and intraclass correlation coefficient (ICC).

Results

The within‐day RMS‐CVs ranged from 2.3% to 7.8%, and the between‐day RMS‐CVs ranged from 4.0% to 7.3% across all parameters. The within‐day ICCs ranged from 0.931 to 0.989, and the between‐day ICCs ranged from 0.934 to 0.971 across all parameters.

Conclusion

These results demonstrate high reproducibility for trabecular bone microarchitecture measures derived from 3T MR images of the proximal femur. The measurement reproducibility is within a range suitable for clinical cross‐sectional and longitudinal studies in osteoporosis. J. Magn. Reson. Imaging 2015;42:1339–1345.
Diagnostic accuracy of diffusion‐weighted MRI for differentiation of cervical cancer and benign cervical lesions at 3.0T: Comparison with routine MRI and dynamic contrast‐enhanced MRI
Authors: Kuang Fei , Yan Zhiping , Li Huili , Feng Hao
Published: March 2015

Purpose

To compare the diagnostic accuracy of routine magnetic resonance imaging (MRI) (T1WI and T2WI), diffusion‐weighted MRI (DWI), and DCE‐MRI (dynamic contrast‐enhanced MRI) at 3.0T for differentiation of cervical cancer and benign cervical lesions.

Materials and Methods

A cohort of 75 cervical cancer patients, 26 cervical leiomyoma patients, 22 patients with cervical polyps consecutively underwent pelvic MRI scanning on a 3T MR unit. Two radiologists independently evaluated images at three imaging settings; routine MRI alone, DWI combined with routine MRI (DWI+routine MRI), and DCE‐MRI. The apparent diffusion coefficients (ADCs) were calculated from b 0, 600 s/mm2 and b 0, 1000 s/mm2.

Results

DWI+routine MRI was significantly better than routine MRI and obtained high accuracy (0.95); the diagnostic performance was not significantly different between DWI+routine MRI and DCE‐MRI. Reader agreement was excellent for both DWI+routine MRI (κ, 0.90) and DCE‐MRI (κ, 0.92). The ADCs of cervical cancer were significantly lower than those of benign cervical lesions at both ADC maps (P = 0.0001). The diagnostic accuracy was not different at both ADC maps (P = 0.375).

Conclusion

For differentiation of cervical cancer and benign cervical lesions, unenhanced MRI with combined diffusion‐weighted and routine MRI (DWI+routine MRI) at 3T can provide accurate information and may be preferable to DCE. J. Magn. Reson. Imaging 2015. J. Magn. Reson. Imaging 2015;42:1094–1099.
Microwave noise modeling for MOSFETs
Authors: Yu Panpan , Chen Bo , Gao Jianjun
Published: March 2015

Analytical expressions for the noise parameters of radio frequency metal oxide semiconductor field effect transistors (MOSFETs) are presented in this paper. These expressions are derived from an accurate small‐signal and noise equivalent circuit model, which takes into account the substrate parasitics and series inductances. Further, simplified expressions for noise parameters in the low‐frequency range are given. Good agreement is obtained between measured and calculated results up to 14 GHz for 0.35 µm MOSFET over a wide range of bias points. Copyright © 2015 John Wiley & Sons, Ltd.
Positive effects of the traditional Chinese medicine MLC901 in cognitive tasks
Authors: Lorivel T. , Gandin C. , Veyssière J. , Lazdunski M. , Heurteaux C.
Published: March 2015

MLC901 (NurAiDII) is used as a treatment for stroke patients. It has been shown that MLC901 improves motor and cognitive recovery in ischemic and traumatic brain‐injured rodents. The present study seeks to delineate cognitive effects induced by MLC901 in normal, noninjured mice. To this end, the behaviors of vehicle‐ and MLC901‐treated C57BL/6 mice in hippocampus‐dependent (passive avoidance, Morris water maze) and hippocampus‐independent (novel object recognition) cognitive tasks are compared. The potential influence of the compound on the anxiety level and nycthemeral rhythm of mice is also assessed. In addition, the long‐term effects of MLC901 on hippocampal neurogenesis are measured. The results clearly demonstrate that MLC901 promotes extinction in passive avoidance and reversal learning in the Morris water maze and improves the performance of mice in novel object recognition. In parallel, this study shows the long‐term proneurogenesis effects of MLC901 that result in the increase in the number of mature neurons in the hippocampus. If these observations can be extended to humans, then MLC901 could represent a promising therapeutic strategy. © 2015 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
A comparison of juice extraction methods in the pungency measurement of onion bulbs
Authors: Yoo Kil Sun , Lee Eun Jin , Hamilton Brian K , Patil Bhimanagouda S
Published: March 2015

BACKGROUND

Onion pungency is estimated by measuring the pyruvic acid content in juice extracted from fresh tissues. We compared pyruvic acid content and its variation in the juices extracted by the pressing, maceration, blending with no water, or blending with water (blend/water) methods.

RESULTS

There were considerable differences in the pyruvic acid content and coefficient of variation (CV) among these methods, and there was an interaction between the onion cultivars and the juice extraction methods. The pressing method showed over 30% CV in the quartered or composite samples. The blend/water method showed the greatest pyruvic acid content in the shortday‐type (‘TG1015Y’ and ‘Texas Early White’) onions, while the pressing method showed the greatest pyruvic acid content in the longday‐type onions. The blend/water method, which gave ratios between 1:1 and 1:4 (w/w), showed the same pyruvic acid content. The blending (no water) method had the highest correlation, followed by the maceration method. The lowest correlations were found with the pressing method and the blend/water method.

CONCLUSIONS

Complete homogenisation of tissues with 1:1 or greater ratios of water was necessary for the maximum consistency and full development of the pyruvic acid reaction for onion pungency measurement. © 2015 Society of Chemical Industry
Pairing call‐response surveys and distance sampling for a mammalian carnivore
Authors: Hansen Sara J. K. , Frair Jacqueline L. , Underwood H. Brian , Gibbs James P.
Published: March 2015

Density estimates accounting for differential animal detectability are difficult to acquire for wide‐ranging and elusive species such as mammalian carnivores. Pairing distance sampling with call‐response surveys may provide an efficient means of tracking changes in populations of coyotes (Canis latrans), a species of particular interest in the eastern United States. Blind field trials in rural New York State indicated 119‐m linear error for triangulated coyote calls, and a 1.8‐km distance threshold for call detectability, which was sufficient to estimate a detection function with precision using distance sampling. We conducted statewide road‐based surveys with sampling locations spaced ≥6 km apart from June to August 2010. Each detected call (be it a single or group) counted as a single object, representing 1 territorial pair, because of uncertainty in the number of vocalizing animals. From 524 survey points and 75 detections, we estimated the probability of detecting a calling coyote to be 0.17 ± 0.02 SE, yielding a detection‐corrected index of 0.75 pairs/10 km2(95% CI: 0.52–1.1, 18.5% CV) for a minimum of 8,133 pairs across rural New York State. Importantly, we consider this an index rather than true estimate of abundance given the unknown probability of coyote availability for detection during our surveys. Even so, pairing distance sampling with call‐response surveys provided a novel, efficient, and noninvasive means of monitoring populations of wide‐ranging and elusive, albeit reliably vocal, mammalian carnivores. Our approach offers an effective new means of tracking species like coyotes, one that is readily extendable to other species and geographic extents, provided key assumptions of distance sampling are met. © 2015 The Wildlife Society.
Pennsylvania's Conservation Reserve Enhancement Program benefits ring‐necked pheasants but not enough to reverse declines
Authors: Pabian Sarah E. , Wilson Andrew M. , Klinger Scott R. , Brittingham Margaret C.
Published: March 2015

In 2000, the Conservation Reserve Enhancement Program (CREP) was started in Pennsylvania as an incentive program for farm owners to restore grassland and riparian areas to improve water quality in the Chesapeake Bay. The grassland restoration part of the program is thought to produce high quality habitat for rapidly declining populations of ring‐necked pheasants. We used data collected via roadside counts from 2001–2002 and 2009–2010 in a 20‐county area in south‐central Pennsylvania to determine whether CREP field establishment during that time period affected pheasant populations. Pheasant abundances responded positively to the amount of CREP cover; the change in abundance between the two time‐periods increased by 3.2% with every unit increase in the percent CREP coverage within 500 m. Changes in relative abundance increased by an additional 21.9% with every unit increase in the percent CREP coverage within 5,000 m of survey routes, indicating additional benefits of CREP when located in the surrounding landscape. Although pheasant abundances responded positively to CREP, they declined across the area by 52% from the 2001–2002 to 2009–2010 time periods, indicating the overall amount of CREP land was inadequate to reverse the population decline. Because only 6.0% of survey stops currently have conditions necessary to support steady or increasing pheasant populations, the amount of additional CREP coverage needed to reverse population declines in the study area is impractical and will need to be used in combination with other management techniques to be successful. © 2015 The Wildlife Society.
Transcartilaginous ear piercing and infectious complications: A systematic review and critical analysis of outcomes
Authors: Sosin Michael , Weissler Jason M. , Pulcrano Marisa , Rodriguez Eduardo D.
Published: March 2015

Objectives/Hypothesis

The purpose of this systematic review was to critically analyze infectious complications and treatment following transcartilaginous ear piercing.

Data Sources

MEDLINE Pubmed database.

Review Methods

A MEDLINE PubMed database search using free text, including “ear chondritis,” “ear perichondritis,” “ear cartilage piercing,” and “auricle piercing,” yielded 483 titles. Based on set inclusion and exclusion criteria, the titles, abstracts, and full text articles were reviewed for inclusion and underwent data extraction. Pooled outcomes are reported.

Results

A total of 29 articles met inclusion criteria, including 66 patients. The mean age of the patients was 18.7 ± 7.6 years (range: 11–49), 87.5% female. Ear deformity was more likely to occur following postpiercing perichondritis of the scapha 100% versus the helix 43% (P = 0.003). Mean duration of symptoms prior to patients seeking medical attention was 6.1 ± 4.1 days. Greater than 5 days of symptoms prior to seeking treatment was significantly more likely to result in hospitalization. Pseudomonas aeruginosa accounted for 87.2% infections. Of the patients with Pseudomonas, 92.3% were hospitalized versus 75% of the patients infected with Staphylococcus aureus. Initial oral antibiotics prescribed did not target the cultured bacterium in 53.3% of cases; of these, 87.5% were hospitalized.

Conclusions

Transcartilaginous postpiercing infection may lead to ear deformity and hospitalization. Patients (customers) and practitioners must be aware of optimal treatment strategies to minimize associated morbidity. Scapha piercing and delay in presentation are associated with poorer outcomes. Pseudomonas is the most common bacterial infection. Initial antibiotic selection must be optimized accordingly. Laryngoscope, 125:1827–1834, 2015
How should unmatched otolaryngology applicants proceed?
Authors: Schwan Josianna , Abaza Mona , Cabrera‐Muffly Cristina
Published: March 2015

Objectives/Hypothesis

To determine the attitudes of otolaryngology residency program directors and chairpersons toward unmatched residency applicants, including whether a surgical internship or research year is preferred in considering repeat applicants.

Study Design

Cross‐sectional survey.

Methods

Approval was obtained from the Colorado Multiple Institution Review Board. A 12‐question Web‐based survey was sent to otolaryngology residency program directors and chairpersons three times over a 6‐week period. Responses collected from respondents were anonymous, with no identifying characteristics.

Results

Forty‐five percent of those contacted responded to the survey. The most commonly recommended course of action for an unmatched applicant was completion of a general surgery intern year (43%) or a year of research (31%). Program directors were more likely than chairpersons to recommend a year of research (P value 0.014). Ninety‐seven percent of the respondents felt it was important or essential to obtain new letters of recommendation. Respondents ranked poor interview skills as the most common reason for applicants remaining unmatched (29%).

Conclusion

Otolaryngology residency match is even more competitive for previously unmatched applicants. Unmatched applicants should be advised to proceed with either a research year or postgraduate year 1 general surgery year. Before applying again, applicants should obtain new letters of recommendation, and the importance of improving poor interviewing skills should be emphasized by advisors.

Level of Evidence

N/A. Laryngoscope, 125:2291–2294, 2015
Pain in cochlear implant recipients: An uncommon, yet serious, consequence of cochlear implantation
Authors: Shapira Yisgav , Yaar‐Soffer Yifat , Hildesheimer Minka , Migirov Lela , Henkin Yael
Published: March 2015

Objectives/Hypothesis

We describe pain around the receiver/stimulator [RS] presenting months to years after implantation.

Study Design

A retrospective chart review.

Methods

We performed a retrospective review of all cochlear implant recipients complaining of pain around their RS through the years 2009 through 2013, with a follow‐up of at least 6 months. Excluded from the study were patients with an identifiable cause for their pain such as trauma, local infection, or skin breakdown. The therapy regimen and outcomes were reviewed.

Results

Thirty patients complained of delayed pain over their RS, representing 2.8% of 1,044 implantations performed at the Sheba Medical Center, Tel Hashomer, Israel, as of 2013. The time from implantation to the presentation of pain ranged from 3 months to 12 years. The pain was perceptible even when the external magnet and processor were not used, and was usually most obvious in specific points around the RS. Seventy‐seven percent of our patients responded well to conservative therapy. Fifteen (50%) responded to prolonged antibiotic treatment. Five patients (17%) responded to antiinflammatories alone. One patient (3%) responded to deactivation of two electrodes. Six patients (20%) required reimplantation, after which the pain resolved in all. At explantation, no signs of infection, foreign body reaction, or obvious device damage were found.

Conclusion

Delayed pain around the RS that is unrelated to use is a serious consequence of cochlear implantation, and in some cases, those necessitating reimplantation, should be considered a major complication.

Level of Evidence

4. Laryngoscope, 125:1946–1951, 2015
Invasion and molecular evolution of Daphnia pulex in Japan
Authors: So Mika , Ohtsuki Hajime , Makino Wataru , Ishida Seiji , Kumagai Hitoshi , Yamaki Kenyu G. , Urabe Jotaro
Published: March 2015

We examined Daphnia pulex in Japan to clarify if they were representative of indigenous populations or colonized recently. Phylogenetic analysis of mtDNA suggests that Japanese lineages of D. pulex are immigrants from North America, and are hybrids formed with Daphnia pulicaria prior to this immigration. Based on the mtDNA sequences, the D. pulex individuals aggregated into four distinct genetic groups (JPN 1‐4) comprising a total of 21 haplotypes. Surprisingly, microsatellite analysis with 12 loci revealed only a single multilocus genotype per genetic group, suggesting that D. pulex populations in Japan are comprised of asexual individuals, derived from only four clones. According to the reported mutation rate of mtDNA, JPN 1 and 2, now widely distributed across Japan, were estimated to have invaded between 680 yr and 3400 yr ago, while JPN 3 and 4 colonized much more recently. Results also indicated that the invasion of some clones could not be attributed to recent human activities and most likely occurred by rare natural events. Since the evolutional longevity of asexual clones is thought to be limited, genetic diversity of D. pulex in Japan has the possibility of decreasing in the near future without addition of novel gene flow.
Liver‐targeted gene therapy: Approaches and challenges
Authors: Aravalli Rajagopal N. , Belcher John D. , Steer Clifford J.
Published: March 2015

The liver plays a major role in many inherited and acquired genetic disorders. It is also the site for the treatment of certain inborn errors of metabolism that do not directly cause injury to the liver. The advancement of nucleic acid–based therapies for liver maladies has been severely limited because of the myriad untoward side effects and methodological limitations. To address these issues, research efforts in recent years have been intensified toward the development of targeted gene approaches using novel genetic tools, such as zinc‐finger nucleases, transcription activator‐like effector nucleases, and clustered regularly interspaced short palindromic repeats as well as various nonviral vectors such as Sleeping Beauty transposons, PiggyBac transposons, and PhiC31 integrase. Although each of these methods uses a distinct mechanism of gene modification, all of them are dependent on the efficient delivery of DNA and RNA molecules into the cell. This review provides an overview of current and emerging therapeutic strategies for liver‐targeted gene therapy and gene repair. Liver Transpl 21:718‐737, 2015. © 2015 AASLD.
Sofosbuvir and simeprevir for treatment of hepatitis C virus infection in liver transplant recipients
Authors: Gutierrez Julio A. , Carrion Andres F. , Avalos Danny , O'Brien Christopher , Martin Paul , Bhamidimarri Kalyan Ram , Peyton Adam
Published: March 2015

Recurrent hepatitis C virus (HCV) infection occurs universally in the allograft in the absence of effective antiviral therapy before liver transplantation (LT). Antiviral therapy with sofosbuvir and simeprevir has proven to be highly effective and well tolerated in the nontransplant setting for treatment of HCV genotype 1 infection; therefore, we sought to evaluate the efficacy and safety of this regimen in LT recipients with recurrent HCV infection. This was a retrospective analysis of a single‐center treatment protocol of patients with HCV genotype 1 infection who received a 12‐week combination regimen of sofosbuvir and simeprevir. Sixty‐one patients (35 with genotype 1a and 26 with genotype 1b) completed treatment with simeprevir and sofosbuvir. Three patients received additional ribavirin. Laboratory data and clinical assessments performed at the baseline, on treatment, at the end of treatment, and 12 weeks after the completion of antiviral therapy [sustained virological response at 12 weeks (SVR12)] were analyzed. The median time after LT was 5.4 years [interquartile range (IQR), 1.9‐8.4 years], and tacrolimus was the most commonly used immunosuppressive agent (80.3%). Overall, SVR12 was achieved in 93.4% [95% confidence interval (CI), 84%‐97%] of LT recipients treated with 12 weeks of sofosbuvir and simeprevir. When they were analyzed according to the HCV subtype, LT recipients with genotype 1b had a 100% SVR12 rate (95% CI, 87%‐100%), whereas SVR12 was 89% (95% CI, 74%‐95%) for those with genotype 1a. Advanced fibrosis (METAVIR F3‐F4) was associated with diminished antiviral efficacy in LT recipients with genotype 1a [SVR12, 67% (95% CI, 39%‐86%); P = 0.01]. Overall, the incidence of adverse events (AEs) was low, and no severe AEs occurred during treatment. In conclusion, treatment with a 12‐week regimen of sofosbuvir and simeprevir was well tolerated and resulted in a high SVR12 rate for LT recipients with recurrent HCV genotype 1 infection. Genotype 1a patients with advanced fibrosis of the allograft were more likely to relapse. Liver Transpl 21:823‐830, 2015. © 2015 AASLD.
Circulating levels of soluble receptor for advanced glycation end products and ligands of the receptor for advanced glycation end products in patients with acute liver failure
Authors: Basta Giuseppina , Del Turco Serena , Navarra Teresa , Lee William M. ,   Acute Liver Failure Study Group
Published: March 2015

Animal studies suggest that receptor for advanced glycation end products (RAGE)–dependent mechanisms contribute to acetaminophen‐induced liver damage. We examined whether circulating levels of soluble receptor for advanced glycation end products (sRAGE) or RAGE ligands, including extracellular newly identified receptor for advanced glycation end products binding protein (EN‐RAGE), high‐mobility group box 1 (HMGB1), and Nε‐(Carboxymethyl)lysine adducts (CML), could aid in prognostication after an acetaminophen overdose. Sixty well‐characterized acetaminophen‐related acute liver failure (ALF) patients (30 spontaneous survivors and 30 patients who underwent transplantation and/or died) who were enrolled in the National Institutes of Health–sponsored Acute Liver Failure Study Group, were matched by age, met standard criteria for encephalopathy, and had an international normalized ratio > 1.5 were retrospectively studied. HMGB1, EN‐RAGE, CML, and sRAGE were detected by enzyme‐linked immunosorbent assay methods in sera from ALF patients and 30 healthy controls. Levels of sRAGE, EN‐RAGE, and HMGB1 (but not CML) were significantly greater (P < 0.001) in ALF patients versus normal controls. The levels of sRAGE, HMGB1, and EN‐RAGE were significantly higher (P = 0.03, P < 0.01, and P = 0.03) in patients with a systemic inflammatory response syndrome (SIRS) score > 2 versus patients with a SIRS score ≤ 2. Nevertheless, only sRAGE levels were significantly higher in patients who underwent transplantation and/or died versus spontaneous survivors (P < 0.001), and they were positively associated with conventional markers of liver disease severity. Multivariate logistic regression identified an encephalopathy grade > 2 as an independent predictor of an adverse outcome on admission (odds ratio, 13; 95% confidence interval, 2.3‐73; P < 0.001). The RAGE‐ligand axis may interfere with liver regeneration and should be a promising objective for further research. Liver Transpl 21:847‐854, 2015. © 2015 AASLD.
Investigation of the inhibition effect of the environmentally friendly inhibitor sodium alginate on magnesium alloy in sodium chloride solution
Authors: Dang N. , Wei Y. H. , Hou L. F. , Li Y. G. , Guo C. L.
Published: March 2015

The corrosion inhibition and adsorption behavior of sodium alginate on AZ31 magnesium alloy in 3.5 wt% sodium chloride solution is investigated. The results show that sodium alginate can effectively inhibit the corrosion of AZ31 magnesium alloy. With increasing sodium alginate concentration, the inhibition efficiency initially increases and then decreases. It reaches a maximum of 90.00% at a sodium alginate concentration of 500 ppm. The inhibition is due to adsorption of sodium alginate on the bare magnesium alloy surface, where it mixes with magnesium hydroxide to form a more continuous and compact film, which retards the corrosion of the alloy.
Synthesis of an Amphiphilic Brush Copolymer by a Highly Efficient “Grafting onto” Approach via CO2 Chemistry
Authors: Zhang Ying‐Ying , Li Yang , Zhou Xian‐Jing , Zhang Xing‐Hong , Du Bin‐Yang , Fan Zhi‐Qiang
Published: March 2015

A novel and robust route for the synthesis of a new amphiphilic brush copolymer, poly(glycidyl methacrylate)‐graft‐polyethylene glycol (PGMA‐g‐PEG), with high grafting densities of 97%–98% through a “grafting onto” method via carbon dioxide chemistry is reported. PGMA‐g‐PEG can self‐assemble and form stable spherical core–shell micelles in aqueous solution. Besides, the obtained PGMA‐g‐PEG polymer contains hydroxyurethane structures as the junction sites between the PGMA backbone and PEG side chain, which can be used for further modification.

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Third Parties and Contract Design: The Case of Contracts for Technology Transfer
Authors: Duplat Valérie , Lumineau Fabrice
Published: March 2015

Given the challenges associated with drafting technology‐transfer contracts, we examine decisions to involve third parties offering technical or legal support in the contract‐drafting process. We first argue that the attributes of the transaction are key drivers of third‐party involvement. We then draw on the behavioral theory of the firm to develop arguments regarding the influence of third parties on contract complexity. Our results reveal that the involvement of legal third parties tends to magnify the contract's overall complexity. In contrast, the involvement of technical third parties reduces the inclusion of monitoring provisions and increases the inclusion of coordination provisions. Copyright © 2015 John Wiley & Sons, Ltd.
Critical roles for WDR72 in calcium transport and matrix protein removal during enamel maturation
Authors: Wang Shih‐Kai , Hu Yuanyuan , Yang Jie , Smith Charles E. , Nunez Stephanie M. , Richardson Amelia S , Pal Soumya , Samann Andrew C. , Hu Jan C.‐C. , Simmer James P.
Published: March 2015

Defects in WDR72 (WD repeat‐containing protein 72) cause autosomal recessive hypomaturation amelogenesis imperfecta. We generated and characterized Wdr72‐knockout/lacZ‐knockin mice to investigate the role of WDR72 in enamel formation. In all analyses, enamel formed by Wdr72 heterozygous mice was indistinguishable from wild‐type enamel. Without WDR72, enamel mineral density increased early during the maturation stage but soon arrested. The null enamel layer was only a tenth as hard as wild‐type enamel and underwent rapid attrition following eruption. Despite the failure to further mineralize enamel deposited during the secretory stage, ectopic mineral formed on the enamel surface and penetrated into the overlying soft tissue. While the proteins in the enamel matrix were successfully degraded, the digestion products remained inside the enamel. Interactome analysis of WDR72 protein revealed potential interactions with clathrin‐associated proteins and involvement in ameloblastic endocytosis. The maturation stage mandibular incisor enamel did not stain with methyl red, indicating that the enamel did not acidify beneath ruffle‐ended ameloblasts. Attachment of maturation ameloblasts to the enamel layer was weakened, and SLC24A4, a critical ameloblast calcium transporter, did not localize appropriately along the ameloblast distal membrane. Fewer blood vessels were observed in the papillary layer supporting ameloblasts. Specific WDR72 expression by maturation stage ameloblasts explained the observation that enamel thickness and rod decussation (established during the secretory stage) are normal in the Wdr72 null mice. We conclude that WDR72 serves critical functions specifically during the maturation stage of amelogenesis and is required for both protein removal and enamel mineralization.
Metabolite and macromolecule T1 and T2 relaxation times in the rat brain in vivo at 17.2T
Authors: Lopez‐Kolkovsky Alfredo L. , Mériaux Sebastien , Boumezbeur Fawzi
Published: March 2015

Purpose

To measure the T1 and T2 relaxation times of water, metabolites, and macromolecules in the rat brain in vivo at 17.2T and achieve absolute quantification of the neurochemical profile. Relaxation times were compared with values from the literature found at lower magnetic fields.

Methods

1H NMR spectra were measured using a LASER localization sequence. T1‐ and T2‐weighted spectra were analyzed using LCModel with an original parameterization of the macromolecule baseline.

Results

The T1 relaxation times of 20 metabolites and the T2 relaxation times of 16 singlets and J‐coupled metabolites were measured. The mean T1 and T2 relaxation times for metabolites were 1721 ± 237 ms and 148 ± 53 ms, respectively. In addition, we measured the T1 and T2 relaxation times of 4 macromolecule resonance groups, their mean T1 and T2 relaxation times being 690 ± 100 ms and 37 ± 15 ms, respectively. Absolute quantification of 21 metabolites and 4 groups of macromolecule resonances was achieved with Cramer‐Rao Lower Bounds below 5% for Cr, Gln, Glu, GPC, Ins, NAA, PCr, and Tau and below 25% for the remaining resonances.

Conclusion

Comparison of our relaxation times to previously published values suggests a small increase of T1 values and a clear decrease of T2 values between 11.7 and 17.2T. Magn Reson Med 75:503–514, 2016. © 2015 Wiley Periodicals, Inc.
Signal‐to‐noise ratio and MR tissue parameters in human brain imaging at 3, 7, and 9.4 tesla using current receive coil arrays
Authors: Pohmann Rolf , Speck Oliver , Scheffler Klaus
Published: March 2015

Purpose

Relaxation times, transmit homogeneity, signal‐to‐noise ratio (SNR) and parallel imaging g‐factor were determined in the human brain at 3T, 7T, and 9.4T, using standard, tight‐fitting coil arrays.

Methods

The same human subjects were scanned at all three field strengths, using identical sequence parameters and similar 31‐ or 32‐channel receive coil arrays. The SNR of three‐dimensional (3D) gradient echo images was determined using a multiple replica approach and corrected with measured flip angle and T2* distributions and the T1 of white matter to obtain the intrinsic SNR. The g‐factor maps were derived from 3D gradient echo images with several GRAPPA accelerations.

Results

As expected, T1 values increased, T2* decreased and the B1‐homogeneity deteriorated with increasing field. The SNR showed a distinctly supralinear increase with field strength by a factor of 3.10 ± 0.20 from 3T to 7T, and 1.76 ± 0.13 from 7T to 9.4T over the entire cerebrum. The g‐factors did not show the expected decrease, indicating a dominating role of coil design.

Conclusion

In standard experimental conditions, SNR increased supralinearly with field strength (SNR ∼ B01.65). To take full advantage of this gain, the deteriorating B1‐homogeneity and the decreasing T2* have to be overcome. Magn Reson Med 75:801–809, 2016. © 2015 Wiley Periodicals, Inc.
Balanced SSFP‐like steady‐state imaging using small‐tip fast recovery with a spectral prewinding pulse
Authors: Sun Hao , Fessler Jeffrey A. , Noll Douglas C. , Nielsen Jon‐Fredrik
Published: March 2015

Purpose

Small‐tip fast recovery (STFR) imaging has been proposed recently as a potential alternative to balanced steady‐state free precession (bSSFP). STFR relies on a tailored “tip‐up” radio‐frequency pulse to achieve comparable signal level as bSSFP, but with reduced banding artifacts and transient oscillations, and is compatible with magnetization‐preparation pulses. Previous STFR implementations used two‐dimensional or three‐dimensional pulses spatially tailored to the accumulated phase calculated from a B0 field map, making the steady‐state STFR signal contain some T2* weighting. Here, we propose to replace the spatially tailored pulse with a recently introduced spectrally selective “pre‐winding” pulse that is precomputed to a target frequency range. The proposed “spectral‐STFR” sequence produces T2/T1‐weighted images similar to bSSFP, but with reduced banding and potentially other benefits.

Theory and Methods

We investigated the steady‐state signal properties of spectral‐STFR using simulations, and phantom and human volunteer experiments.

Results

Our simulation and experimental results showed that the spectral‐STFR sequence has similar signal level and tissue contrast as bSSFP, but has a wider passband and more consistent banding profiles across different tissues (e.g., less hyperintense signal at band edges for low flip angles). Care is needed in designing the spectral radio‐frequency pulse to ensure that the small tip angle approximation holds during radio‐frequency transmission.

Conclusion

Spectral‐STFR has similar tissue contrast as bSSFP but a wider passband and more consistent cerebrospinal fluid/brain tissue contrast across the passband. The spectral‐STFR sequence is a potential alternative to bSSFP in some applications. Compared to a spatially tailored STFR sequence, spectral‐STFR can be precomputed, is easier to implement in practice, and potentially has more uniform image contrast and minimal T2* weighting. Magn Reson Med 75:839–844, 2016. © 2015 Wiley Periodicals, Inc.
Preparation and properties of phenyl‐modified natural rubber
Authors: Kawahara Seiichi , Shioyama Shintaro , Nuorn Choothong , Fukuhara Lina , Ishii Hiroyuki , Yamamoto Yoshimasa , Takenaka Katsuhiko
Published: March 2015

We prepared phenyl‐modified natural rubber using a two‐step process. In the first step, natural rubber was brominated using N‐bromosuccinimide in a dichloromethane solution of natural rubber. The amount of N‐bromosuccinimide controlled the bromine content. In the second step, a Suzuki–Miyaura cross‐coupling reaction of the brominated natural rubber with phenyl boronic acid in the presence of a palladium catalyst replaced the bromine atoms with phenyl groups. 1H‐nuclear magnetic resonance and 13C‐nuclear magnetic resonance measurements characterized the products. The signals around 7 ppm in the 1H‐nuclear magnetic resonance spectra of the products were assigned to the phenyl protons, and based on the assigned signals, the estimated conversion of the cross‐coupling reaction under mild conditions was more than 70 mol%. The amount of phenyl groups present affected both the loss tangent and the glass transition temperature of natural rubber, which increases from −62°C to −30°C. Copyright © 2015 John Wiley & Sons, Ltd.
Hydrophilic–hydrophobic properties of SiOH‐loaded and modified polysiloxane microspheres and their interaction with γ‐globulin
Authors: Mizerska Urszula , Fortuniak Witold , Pospiech Piotr , Sobczak Aleksandra , Chojnowski Julian , Slomkowski Stanislaw
Published: March 2015

Adsorption of human γ‐globulin on hydrophilic polysiloxane microspheres was investigated. The microspheres contained a large number of silanol groups, and their modified derivatives were enriched with a limited number of hydrophobic groups. Hydrophilic–hydrophobic properties of these particles were compared using Rose Bengal as a hydrophobic probe. Polysiloxane microspheres were modified by addition of hydrophobic isopropoxy side groups to polyhydromethylsiloxane, the precursor polymer of the hydrophilic microspheres. Hydrophilic particles were modified also by trimethylsilylation. These modifications allowed to control the hydrophilic–hydrophobic properties of the microspheres and modification of their ability for protein adsorption. In water suspension, the unmodified microspheres containing silanol groups showed no affinity to hydrophobic Rose Bengal dye. The unspecific adsorption of γ‐globulin on these microspheres was at a much lower level than that on particles silylated with some amount of trimethylchlorosilane and trimethylethoxysilane. The presence of bulky hydrophobic isopropoxy groups attached to polyhydromethylsiloxane decreased the formation of silanol groups during the fabrication of particles. A moderate enhancement of protein affinity to these particles may be achieved in this way. Copyright © 2015 John Wiley & Sons, Ltd.