bluuebunny/crossref_metadata_2025 huggingface dataset:
A storm of fast (40–150Hz) oscillations during hypsarrhythmia in West syndrome
Authors: Kobayashi Katsuhiro , Akiyama Tomoyuki , Oka Makio , Endoh Fumika , Yoshinaga Harumi
Published: November 2014

Objective

Fast oscillations (FOs) were first explored from scalp electroencephalographic (EEG) data from hypsarrhythmia in West syndrome (infantile spasms) to investigate the meaning of FOs in this epileptic encephalopathy.

Methods

In 17 infants with West syndrome, we conservatively detected fast frequency peaks that stood out from the time‐frequency spectral background with square root power > 1µV (spectral criterion) and corresponded to clear FOs with at least 4 oscillations in the filtered EEG traces (waveform criterion) in sleep EEGs.

Results

We found a total of 1,519 interictal FOs that fulfilled both the spectral and waveform criteria. The FOs with a median frequency of 56.6Hz (range = 41.0–140.6Hz) were dense, with a median rate of 66 (range = 24–171) per minute before adrenocorticotropic hormone (ACTH) treatment, which was significantly higher than that in control infants without seizures (median = 1, p < 0.001). The FOs were reduced by treatment. The mean gamma and ripple oscillation rates that were detected using the waveform criterion alone were 40.62/min and 15.75/min, respectively, per channel; these results were 112.8 and 98.4 times higher, respectively, than the previously reported corresponding rates in adult epilepsy patients.

Interpretation

The observed FOs corresponded to epileptogenicity because of their close relation to the severity of hypsarrhythmia during the course of ACTH treatment. The very high epileptic FO rates in hypsarrhythmia are thought to affect the process of neurodevelopment by interfering with physiological functions in West syndrome, taking into account that high frequencies are also important in physiological higher brain functions. ANN NEUROL 2015;77:58–67
Durability and performance of polystyrene‐b‐poly(vinylbenzyl trimethylammonium) diblock copolymer and equivalent blend anion exchange membranes
Authors: Vandiver Melissa A. , Caire Benjamin R. , Poskin Zach , Li Yifan , Seifert Sönke , Knauss Daniel M. , Herring Andrew M. , Liberatore Matthew W.
Published: November 2014

Anion exchange membranes (AEM) are solid polymer electrolytes that facilitate ion transport in fuel cells. In this study, a polystyrene‐b‐poly(vinylbenzyl trimethylammonium) diblock copolymer was evaluated as potential AEM and compared with the equivalent homopolymer blend. The diblock had a 92% conversion of reactive sites with an IEC of 1.72 ± 0.05 mmol g−1, while the blend had a 43% conversion for an IEC of 0.80 ± 0.03 mmol g−1. At 50°C and 95% relative humidity, the chloride conductivity of the diblock was higher, 24–33 mS cm−1, compared with the blend, 1–6 mS cm−1. The diblock displayed phase separation on the length scale of 100 nm, while the blend displayed microphase separation (∼10 μm). Mechanical characterization of films from 40 to 90 microns thick found that elasticity and elongation decreased with the addition of cations to the films. At humidified conditions, water acted as a plasticizer to increase film elasticity and elongation. While the polystyrene‐based diblock displayed sufficient ionic conductivity, the films' mechanical properties require improvement, i.e., greater elasticity and strength, before use in fuel cells. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41596.
Effect of consanguinity on birth defects in Saudi women: Results from a nested case‐control study
Authors: Majeed‐Saidan Muhammad Ali , Ammari Amer N. , AlHashem Amal M. , Al Rakaf Maha S. , Shoukri Mohamed M. , Garne Ester , Kurdi Ahmed Mohammed
Published: November 2014

Background

The role of consanguinity in the etiology of structural birth defects outside of chromosomal and inherited disorders has always been debated. We studied the independent role of consanguinity on birth defects in Saudi women with a high prevalence of consanguineous marriages.

Methods

This case and control study was nested within a 3‐year prospective cohort study to examine patterns of fetal and neonatal malformations in Saudi women at Prince Sultan Military Medical City (PSMMC), Riyadh ‐Saudi Arabia. Consanguineous marriages were defined as marriages with first or second cousins (related); unions beyond second cousins (distant relatives) were considered unrelated for this study.

Results

During the 3‐year study (July 2010 through June 2013), there were 28,646 total births; of these, we included 1,179 babies with major birth defects, and 1,262 babies as their controls. The consanguinity prevalence for all included women was 49.6%. The consanguinity among babies with major Birth Defects (BDs) was 54.5% and 45.2% for controls (P < 0.0002). The prevalence of major birth defects was 41.1 per 1000 total births. Univariate analysis showed that consanguinity had a statistically significant contribution in babies born with genetic syndromes, isolated renal defects, and isolated other defects (P < 0.05). Multivariate logistic regression analyses showed that consanguinity was an independent risk factor for this high prevalence of birth defects in the study population (P < 0.0002).

Conclusion

The prevalence of major birth defects in the study population is higher than what is reported from European countries. Consanguinity is a significant independent risk factor for the high prevalence of birth defects. Birth Defects Research (Part A) 103:100–104, 2015 © 2014 Wiley Periodicals, Inc.
Effect of a buried ion pair in the hydrophobic core of a protein: An insight from constant pH molecular dynamics study
Authors: Pathak Arup K.
Published: November 2014

Constant pH molecular dynamics (CpHMD) is a commonly used sampling method, which incorporates the coupling of conformational flexibility and protonation state of a protein during the simulation by using pH as an external parameter. The effects on the structure and stability of a hyperstable variant of staphylococcal nuclease (Δ+PHS) protein of an artificial charge pair buried in its hydrophobic core are investigated by applying both CpHMD and accelerated molecular dynamics coupled with constant pH (CpHaMD) methods. Generalized Born electrostatics is used to model the solvent water. Two sets of starting coordinates of V23E/L36K variant of Δ+PHS, namely, Maestro generated coordinates from Δ+PHS and crystal structure coordinates of the same are considered for detail investigations. On the basis of root mean square displacement (RMSD) and root mean square fluctuations (RMSF) calculations, it is observed that this variant is stable over a wide range of pH. The calculated pKa values for aspartate and glutamate residues based on both CpHMD and CpHaMD simulations are consistent with the reported experimental values (within ± 0.5 to ± 1.5 pH unit), which clearly indicates that the local chemical environment of the carboxylic acids in V23E/L36K variant are comparable to the parent form. The strong salt bridge interaction between the mutated pair, E23/K36 and additional hydrogen bonds formed in the V23E/L36K variant, may help to compensate for the unfavorable self‐energy experienced by the burial of these residues in the hydrophobic core. However, from RMSD, RMSF, and pKa analysis, no significant change in the global conformation of V23E/L36K variant with respect to the parent form, Δ+PHS is noticed. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 148–157, 2015.
Biophysical properties and thermal stability of oligonucleotides of RNA containing 7,8‐dihydro‐8‐hydroxyadenosine
Authors: Chauca‐Diaz Ana M. , Jung Choi Yu , Resendiz Marino J. E.
Published: November 2014

Circular dichroism (CD) was used to assess the stabilization/destabilization imposed by oxidative lesion 7,8‐dihydro‐8‐hydroxyadenosine (8‐oxoA) on strands of RNA with different structural motifs. RNA:RNA homoduplex destabilization was observed in a position dependent manner using 10‐mers as models that displayed differences between 12.7 and 15.1°C. We found that increasing the number of modifications resulted in depressed Tm values of about 12–15°C per lesion. The same effect was observed on RNA:DNA heteroduplex samples. We also tested the effects of this lesion in short hairpins containing the tetraloop UUCX (X = A, 8‐oxoA). We found that the stem was hypersensitive to substitution of A by 8‐oxoA and that it destabilized the structure by >23°C. Concomitant substitution at the stem and loop prevented formation of this secondary structure or lead to other less‐stable hairpins. Incorporation of this lesion at the first base of the loop had no effect on either structure. Overall, we found that the effects of 8‐oxoA on RNA structure are position dependent and that its stabilization may vary from sharp decreases to small increments, in some cases, leading to the formation of other more/less stable structures. These structural changes may have larger biological implications, particularly if the oxidatively modified RNA persists, thus leading to changes in RNA reactivity and function. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 167–174, 2015.
Helical screw‐sense preferences of peptides based on chiral, Cα‐tetrasubstituted α‐amino acids
Authors: Crisma Marco , Toniolo Claudio
Published: November 2014

The preferred helical screw senses of chiral α‐amino acids with a Cα‐tetrasubstituted α‐carbon atom, as determined in the crystal state by X‐ray diffraction analyses on derivatives and peptides, are reviewed. This survey covers Cα‐methylated and Cα‐ethylated α‐amino acids, as well as α‐amino acids cyclized on the α‐carbon, including those characterized by the combination of lack of chirality at the α‐carbon with either side‐chain or axial chirality. Although, in general, chiral Cα‐tetrasubstituted α‐amino acids show a less pronounced bias toward a single helical screw sense than their proteinogenic (Cα‐trisubstituted) counterparts, our analysis highlights significant differences in terms of magnitude and direction of such a bias among the various sub‐families of residues, and between individual amino acids within each sub‐family as well. The experimental findings can be rationalized, at least in part, on the basis of steric considerations. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 46–64, 2015.
Unusual presentation of tuberculosis in an elderly male: a case report
Authors: Kandel Ramesh , Bhattarai Bhawana , Maharjan Santosh
Published: November 2014

Key Clinical Message

Tuberculous liver abscess is an extremely rare condition, even in tuberculosis endemic countries. A 68‐year‐old male presented with 2 months of fever, significant weight loss, and hepatomegaly. Ultrasonography revealed a right hepatic lobe abscess. Guided aspiration of the fluid showed tubercular bacilli. He had no evidence of active Tuberculosis elsewhere.
Paired Electrosynthesis of Diacid and Diol Precursors Using Dienes and CO2 as the Carbon Source
Authors: Matthessen Roman , Fransaer Jan , Binnemans Koen , De Vos Dirk E.
Published: November 2014

A new electrochemical methodology was devised and optimized, allowing a net incorporation of carbon dioxide in conjugated dienes in a one‐compartment cell using a non‐sacrificial anode. This divergent paired electrosynthesis of diacid and diol precursors was achieved through simultaneous cathodic carboxylation and anodic acetoxylation of conjugated dienes. After optimization of the reaction conditions, 1,3‐cyclohexadiene was converted to its corresponding 1,4‐dicarboxylate salt and 1,4‐diacetate ester with high yields and current efficiencies. A large effect of alkyl substitution and molecular configuration on the reactivity of conjugated double bonds towards carboxylation and acetoxylation was observed.
Anaerobic co‐digestion of dairy cattle slurry and agro‐industrial fats: Effect of fat ratio on the digester efficiency
Authors: Guillaume Sébastien , Lendormi Thomas
Published: November 2014

The objective of the study was to optimize the co‐digestion of cattle slurry in the presence of fats from the food industry. A laboratory pilot plant operating continuously was used for the experimental study. Tests were carried out with only cattle slurry and with different fat ratio (0, 10, 25, 45 and 60 %w/w of the feed COD as fats). In the case of using cattle slurry feed and OLR from 0.4 and 3.0 kg VS · m−3 · day−1 (HRT between 125 days and 19 days), methane productivity versus OLR exhibit a linear relation reflecting optimum biodegradability of the organic matter. For OLR above 3 kg VS · m−3 · day−1 (HRT less than 19 days), a break in the slope is observed expressing a decrease of the organic matter degradation rate. For HRT equal to 30 days, the results show that fat incorporation ratio lower than 25 %w/w does not affect the digester operation while maintaining acceptable biodegradability of the fat. In contrast, with a fat ratio of 60 %w/w, the system became unstable and a significant decrease in the methane productivity was observed, due to an accumulation of undegraded Long Chain Fatty Acids (LCFA). The conclusion is that the fat ratio must be controlled to avoid the destabilization of digestion, and finally operational conditions are proposed for co‐digestion.
Towards the modelling of a heat‐exchanger reactor by a dynamic approach
Authors: Marin Gallego Juan Carlos , Olivier‐Maget Nelly , Hetreux Gilles , Gabas Nadine , Cabassud Michel
Published: November 2014

The aim of this paper is to present the development of a simulation tool in order to assess the inherently safe characteristics of a heat‐exchanger reactor (HEX) operating reaction systems. The modelling of steady and transient states of a HEX reactor is performed following a hybrid dynamic approach. The global dynamic behaviour of this reactor can be represented by several continuous models, which are bounded by state or time events. Each continuous model is defined as a system of partial differential‐algebraic equations. The numerical scheme is based on the method of lines. Special attention is paid to the model initialization and a simulation strategy of the start‐up phase is presented. The validation of the model is made by numerous examples, such as the simulation of an exothermic reaction.
A mixed‐methods examination of communication between oncologists and primary care providers among primary care physicians in underserved communities
Authors: Shen Megan Johnson , Binz‐Scharf Maria , D'Agostino Tom , Blakeney Natasha , Weiss Elisa , Michaels Margo , Patel Shilpa , McKee M. Diane , Bylund Carma L.
Published: November 2014

BACKGROUND

Research has demonstrated that communication and care coordination improve cancer patient outcomes. To improve communication and care coordination, it is important to understand primary care providers' (PCPs') perceptions of communication with oncologists as well as PCPs' communication needs.

METHODS

A mixed‐methods approach was used in the present study. In the qualitative phase of the study, 18 PCPs practicing in underserved, minority communities were interviewed about their experiences communicating with oncologists. In the quantitative phase of the study, 128 PCPs completed an online survey about their preferences, experiences, and satisfaction with communication with oncologists.

RESULTS

Results indicated a PCP‐oncologist gap in communication occurred between diagnosis and treatment. PCPs wanted more communication with oncologists, updates on their patients' prognosis throughout treatment, and to be contacted via telephone or email and saw their role as crucial in providing supportive care for their patients.

CONCLUSIONS

Although PCPs recognize that they play a critical, proactive role in supporting patients throughout the continuum of their cancer care experience, existing norms regarding postreferral engagement and oncologist‐PCP communication often hinder activation of this role among PCPs. Expected standards regarding the method, frequency, and quality of postreferral communication should be jointly articulated and made accountable between PCPs and oncologists to help improve cancer patients' quality of care, particularly in minority communities. Cancer 2015;121:908–915. © 2014 American Cancer Society.
Analysis of accessing to the nearest and to the strongest base station in femtocell networks
Authors: Zhang Huanle , Liu Jian , Shi Haili
Published: November 2014

The deployment of femtocells can effectively improve the capacity of cellular networks without significant increase in the network management costs. Femtocell base stations are usually installed by users, which poses unique challenges for future mobile communication standards. The randomness of the locations of femtocells brings us many difficulties to analyze and compare. In this paper, we explore the performance on two different access methods under Rayleigh fading channel: accessing to the nearest and accessing to the strongest femtocell base station. Two performance indexes are of most interest in this paper: how the different path loss exponents and femtocell densities affect the difference of performance between the two different access methods. In the first part of this paper, the distributions of received strength for both access methods are achieved, in which we elaborate the characteristics of received signal strength including the cumulative distribution and the median signal strength. In the second part, we explore the characteristic of SINR distribution, which can be interpreted as the probability of coverage. This paper provides detailed illustrations about how performance changes for these two different access methods under Rayleigh fading channel. All results are mathematically tractable. Copyright © 2014 John Wiley & Sons, Ltd.
Cooperative wireless localization based on weighting for vector‐addition error
Authors: Cui Qimei , Shi Yulong , Zhang Xuefei , Tao Xiaofeng
Published: November 2014

Localization error occurrence due to a position ambiguity is a very critical problem in wireless distributed cooperative localization, which may, in turn, affect the reliability of the localization of the whole or a major portion of the network. In this paper, we formulate a two‐dimensional cooperative localization model via graph partition in arbitrary topologies while considering the cooperative node's (or neighbor's) position ambiguity. Based on this model, we establish a robust algorithm, named weighted factor graph (FG)‐based cooperative localization algorithm, by mapping local topologies into the FG and by incorporating the vector‐addition error as the weight. The vector‐addition error includes the measurement error and the neighbor's position ambiguity, simultaneously. The optimal weight is derived theoretically according to the statistic properties of the vector errors and the joint probability density function. Theoretical analysis and numerical results indicate that the proposed algorithm can acquire higher level of accuracy for localization in various topology scenarios in comparison with some typical algorithms. Copyright © 2014 John Wiley & Sons, Ltd.
Development of the innervation of the human inner ear
Authors: Pechriggl Elisabeth J. , Bitsche Mario , Glueckert Rudolf , Rask‐Andersen Helge , Blumer Michael J. F. , Schrott‐Fischer Annelies , Fritsch Helga
Published: November 2014

Studies on the formation of neuronal structures of the human cochlea are rare, presumptively, due to the difficult accessibility of specimens, so that most investigations are performed on mouse models. By means of immunohistochemical and transmission electron microscopic techniques, we investigated an uninterrupted series of unique specimens from gestational week 8 to week 12. We were able to demonstrate the presence of nerve fibers in the prosensory domain at gestational week 8, followed by afferent synaptogenesis at week 11. We identified PAX2 as an early marker for hair cell differentiation. Glutamine synthetase‐positive peripheral glial cells occurred at the beginning of week 8. Transcription factor MAF B was used to demonstrate maturation of the spiral ganglion neurons. The early expression of tyrosine hydroxylase could be assessed. This study provides insights in the early assembly of the neural circuit and organization in humans. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 683–702, 2015
Two new targeted alleles for the comprehensive analysis of Meis1 functions in the mouse
Authors: González‐Lázaro Mónica , Roselló‐Díez Alberto , Delgado Irene , Carramolino Laura , Sanguino María Angeles , Giovinazzo Giovanna , Torres Miguel
Published: November 2014

Meis1 is a highly conserved transcription factor that is activated in a regionally restricted manner from early stages of development. Meis1 belongs to the three amino acid loop extension (TALE) homeodomain family. Together with Pbx1, Meis1 plays a major role as a Hox cofactor, and therefore, plays an essential role in the development of several embryonic organs and systems, including limbs, heart, blood, and vasculature. In addition, Meis1 is required for the development of Hox‐free embryonic regions and interacts with non‐Hox homeodomain and non‐homeodomain transcription factors. During post‐natal life Meis1 is involved in adult cardiomyocyte homeostasis and has been associated with pre‐disposition to human neural and cardiac pathologies. Given the relevance of this transcription factor, we have developed two new Meis1 gene knockin models; a direct ECFP knockin insertion that allows the direct identification of Meis1‐expressing cells in living tissues, and a CreERT2 insertion that allows the inducible genetic tracing of Meis1‐expressing cells in a time‐controlled manner. Importantly, these two alleles represent the first Meis1 mutations in which Meis1 protein production is completely eliminated. These newly targeted Meis1 alleles will be valuable tools to further our understanding of the role of this critical transcription factor during development and disease. genesis 52:967–975, 2014. © 2014 Wiley Periodicals, Inc.
Bioaccumulation of metals and metalloids in medicinal plant Ipomoea pes-caprae from areas impacted by tsunami
Authors: Kozak Lidia , Kokociński Mikołaj , Niedzielski Przemysław , Lorenc Stanisław
Published: November 2014

Tsunami events may have an enormous impact on the functioning of aquatic and terrestrial ecosystems by altering various relationships with biotic components. Concentrations of acid-leachable fractions of heavy metals and metalloids in soils and plant samples from areas affected by the December 2004 tsunami in Thailand were determined. Ipomoea pes-caprae, a common plant species growing along the seashore of this region, and frequently used in folk medicine, was selected to assess the presence of selected elements. Elevated amounts of Cd, Pb, Zn, and As in soil samples, and Pb, Zn, As, Se, Cr, and Ni in plant samples were determined from the tsunami-impacted regions for comparison with reference locations. The flowers of Ipomoea pes-caprae contained the highest amounts of these metals, followed by its leaves, and stems. In addition, its bioaccumulation factor (BAF) supports this capability of high metal uptake by Ipomoea pes-caprae from the areas affected by the tsunami in comparison with a reference site. This uptake was followed by the translocation of these elements to the various plant components. The presence of these toxic metals in Ipomoea pes-caprae growing in contaminated soils should be a concern of those who use this plant for medicinal purposes. Further studies on the content of heavy metals and metalloids in this plant in relation to human health concerns are recommended. Environ Toxicol Chem 2014;9999:1–6. © 2014 SETAC
Environmental fate of emamectin benzoate after tree micro injection of horse chestnut trees
Authors: Burkhard Rene , Binz Heinz , Roux Christian A. , Brunner Matthias , Ruesch Othmar , Wyss Peter
Published: November 2014

Emamectin benzoate, an insecticide derived from the avermectin family of natural products, has a unique translocation behavior in trees when applied by tree micro injection (TMI), which can result in protection from insect pests (foliar and borers) for several years. Active ingredient imported into leaves was measured at the end of season in the fallen leaves of treated horse chestnut (Aesculus hippocastanum) trees. The dissipation of emamectin benzoate in these leaves seems to be biphasic and depends on the decomposition of the leaf. In compost piles, where decomposition of leaves was fastest, a cumulative emamectin benzoate degradation half-life time of 20 d was measured. In leaves immersed in water, where decomposition was much slower, the degradation half-life time was 94 d, and in leaves left on the ground in contact with soil, where decomposition was slowest, the degradation half-life time was 212 d. The biphasic decline and the correlation with leaf decomposition might be attributed to an extensive sorption of emamectin benzoate residues to leaf macromolecules. This may also explain why earthworms ingesting leaves from injected trees take up very little emamectin benzoate and excrete it with the feces. Furthermore, no emamectin benzoate was found in water containing decomposing leaves from injected trees. It is concluded, that emamectin benzoate present in abscised leaves from horse chestnut trees injected with the insecticide is not available to nontarget organisms present in soil or water bodies. Environ Toxicol Chem 2014;9999:1–6. © 2014 The Authors. Published 2014 SETAC
Sex differences in cognitive regulation of psychosocial achievement stress: Brain and behavior
Authors: Kogler Lydia , Gur Ruben C. , Derntl Birgit
Published: November 2014

Although cognitive regulation of emotion has been extensively examined, there is a lack of studies assessing cognitive regulation in stressful achievement situations. This study used functional magnetic resonance imaging in 23 females and 20 males to investigate cognitive downregulation of negative, stressful sensations during a frequently used psychosocial stress task. Additionally, subjective responses, cognitive regulation strategies, salivary cortisol, and skin conductance response were assessed. Subjective response supported the experimental manipulation by showing higher anger and negative affect ratings after stress regulation than after the mere exposure to stress. On a neural level, right middle frontal gyrus (MFG) and right superior temporal gyrus (STG) were more strongly activated during regulation than nonregulation, whereas the hippocampus was less activated during regulation. Sex differences were evident: after regulation females expressed higher subjective stress ratings than males, and these ratings were associated with right hippocampal activation. In the nonregulation block, females showed greater activation of the left amygdala and the right STG during stress than males while males recruited the putamen more robustly in this condition. Thus, cognitive regulation of stressful achievement situations seems to induce additional stress, to recruit regions implicated in attention integration and working memory and to deactivate memory retrieval. Stress itself is associated with greater activation of limbic as well as attention areas in females than males. Additionally, activation of the memory system during cognitive regulation of stress is associated with greater perceived stress in females. Sex differences in cognitive regulation strategies merit further investigation that can guide sex sensitive interventions for stress‐associated disorders. Hum Brain Mapp 36:1028–1042, 2015. © 2014 Wiley Periodicals, Inc.
The Relationship between Coworker Incivility, Emotional Exhaustion, and Organizational Outcomes: The Mediating Role of Emotional Exhaustion
Authors: Hur Won‐Moo , Kim Byung‐Soo , Park Sung‐Jae
Published: November 2014

The aim of this research is to investigate the relationship between coworker incivility, emotional exhaustion, and organizational outcomes measured by job satisfaction, job performance, and turnover intention. Working with a sample of 286 retail bank employees in South Korea, structural equation modeling is employed to test four hypotheses drawing on conservation of resources (COR) theory and affective events theory (AET). According to the analyses, while employee incivility positively affects emotional exhaustion, emotional exhaustion has a negative effect on job satisfaction and job performance. In addition, emotional exhaustion has a positive impact on turnover intention among organizational employees. These results imply that to better understand the relationship between coworker incivility and organizational outcomes, it is necessary to consider emotional exhaustion as an important mediating variable. The theoretical and practical implications of this study are discussed, together with its limitations and future research directions.
Progestin and antiprogestin responsiveness in breast cancer is driven by the PRA/PRB ratio viaAIB1 or SMRT recruitment to the CCND1 and MYC promoters
Authors: Wargon Victoria , Riggio Marina , Giulianelli Sebastián , Sequeira Gonzalo R. , Rojas Paola , May María , Polo María L. , Gorostiaga María A. , Jacobsen Britta , Molinolo Alfredo , Novaro Virginia , Lanari Claudia
Published: November 2014

There is emerging interest in understanding the role of progesterone receptors (PRs) in breast cancer. The aim of this study was to investigate the proliferative effect of progestins and antiprogestins depending on the relative expression of the A (PRA) and B (PRB) isoforms of PR. In mifepristone (MFP)‐resistant murine carcinomas antiprogestin responsiveness was restored by re‐expressing PRA using demethylating agents and histone deacetylase inhibitors. Consistently, in two human breast cancer xenograft models, one manipulated to overexpress PRA or PRB (IBH‐6 cells), and the other expressing only PRA (T47D‐YA) or PRB (T47D‐YB), MFP selectively inhibited the growth of PRA‐overexpressing tumors and stimulated IBH‐6‐PRB xenograft growth. Furthermore, in cells with high or equimolar PRA/PRB ratios, which are stimulated to proliferate in vitro by progestins, and are inhibited by MFP, MPA increased the interaction between PR and the coactivator AIB1, and MFP favored the interaction between PR and the corepressor SMRT. In a PRB‐dominant context in which MFP stimulates and MPA inhibits cell proliferation, the opposite interactions were observed. Chromatin immunoprecipitation assays in T47D cells in the presence of MPA or MFP confirmed the interactions between PR and the coregulators at the CCND1 and MYC promoters. SMRT downregulation by siRNA abolished the inhibitory effect of MFP on MYC expression and cell proliferation. Our results indicate that antiprogestins are therapeutic tools that selectively inhibit PRA‐overexpressing tumors by increasing the SMRT/AIB1 balance at the CCND1 and MYC promoters.
The nuclear bile acid receptor FXR controls the liver derived tumor suppressor histidine‐rich glycoprotein
Authors: Deuschle Ulrich , Birkel Manfred , Hambruch Eva , Hornberger Martin , Kinzel Olaf , Perović‐Ottstadt Sanja , Schulz Andreas , Hahn Ulrike , Burnet Michael , Kremoser Claus
Published: November 2014

The nuclear bile acid receptor Farnesoid X receptor (FXR) is strongly expressed in liver and intestine, controls bile acid and lipid homeostasis and exerts tumor‐protective functions in liver and intestine. Histidine‐rich glycoprotein (HRG) is an abundant plasma protein produced by the liver with the proposed function as a pattern recognition molecule involved in the clearance of immune complexes, necrotic cells and pathogens, the modulation of angiogenesis, the normalization of deranged endothelial vessel structure in tumors and tumor suppression. FXR recognition sequences were identified within a human HRG promoter fragment that mediated FXR/FXR‐agonist dependent reporter gene activity in vitro. We show that HRG is a novel transcriptional target gene of FXR in human hepatoma cells, human upcyte® primary hepatocytes and 3D human liver microtissues in vitro and in mouse liver in vivo. Prolonged administration of the potent nonsteroidal FXR agonist PX20606 increases HRG levels in mouse plasma. Finally, daily oral administration of this FXR agonist for seven days resulted in a significant increase of HRG levels in the plasma of healthy human male volunteers during a clinical Phase I safety study. HRG might serve as a surrogate marker indicative of liver‐specific FXR activation in future human clinical studies. Furthermore, potent FXR agonists might be beneficial in serious health conditions where HRG is reduced, for example, in hepatocellular carcinoma but also other solid cancers, liver failure, sepsis and pre‐eclampsia.
Lenz-Majewski Hyperostotic Dwarfism with Hyperphosphoserinuria from a Novel Mutation in PTDSS1 Encoding Phosphatidylserine Synthase 1
Authors: Whyte Michael P , Blythe Amanda , McAlister William H , Nenninger Angela R , Bijanki Vinieth N , Mumm Steven
Published: November 2014

Lenz-Majewski hyperostotic dwarfism (LMHD) is an ultra-rare Mendelian craniotubular dysostosis that causes skeletal dysmorphism and widely distributed osteosclerosis. Biochemical and histopathological characterization of the bone disease is incomplete and nonexistent, respectively. In 2014, a publication concerning five unrelated patients with LMHD disclosed that all carried one of three heterozygous missense mutations in PTDSS1 encoding phosphatidylserine synthase 1 (PSS1). PSS1 promotes the biosynthesis of phosphatidylserine (PTDS), which is a functional constituent of lipid bilayers. In vitro, these PTDSS1 mutations were gain-of-function and increased PTDS production. Notably, PTDS binds calcium within matrix vesicles to engender hydroxyapatite crystal formation, and may enhance mesenchymal stem cell differentiation leading to osteogenesis. We report an infant girl with LMHD and a novel heterozygous missense mutation (c.829T>C, p.Trp277Arg) within PTDSS1. Bone turnover markers suggested that her osteosclerosis resulted from accelerated formation with an unremarkable rate of resorption. Urinary amino acid quantitation revealed a greater than sixfold elevation of phosphoserine. Our findings affirm that PTDSS1 defects cause LMHD and support enhanced biosynthesis of PTDS in the pathogenesis of LMHD. © 2014 American Society for Bone and Mineral Research.
A possible link between wildfire aerosol and North American Monsoon precipitation in Arizona–New Mexico
Authors: McKendry Ian G. , Gutzler David S.
Published: November 2014

Previous research highlights the dominant role of Pacific sea surface temperatures (SSTs) and their associated large‐scale teleconnections in modulating the North American monsoon (NAM). At the regional scale, feedbacks associated with land‐surface boundary conditions have been shown to provide ‘memory’ in the system. Here, a previously unexplored second‐order linkage between aerosol generated by late‐spring wildfires and subsequent summer precipitation delivered by the NAM in the Arizona‐New Mexico (AZNM) region is proposed. Correlations between June/July organic carbon and elemental carbon (OC/EC) in Inter‐agency Monitoring of Protected Visual Environments (IMPROVE) aerosol data (Gila Wilderness and Bandelier) and NAM precipitation in southern AZNM over the period 1994–2012 are shown to be negative (r = –0.4), suggesting that active antecedent wildfire seasons tend to be immediately followed by a weak late summer monsoon. This result is consistent with a previous study linking precipitation and area burned in wildfires in AZNM. A survey of extant literature suggests a sound basis for potential mechanisms related to convective processes and cloud microphysics, and furthermore suggests that this forcing could be of similar magnitude to well‐documented land‐based second‐order NAM forcings (antecedent snowpack and soil moisture, vegetation, and mineral dust). Based on these results, we believe that the role of aerosols in modulating summer precipitation deserves further investigation both observationally and in modeling studies. If indeed wildfire smoke does contribute to the modulation of NAM intensity, by virtue of its close temporal association with NAM season, it may well represent a factor that could contribute effectively to improved seasonal prediction of summer precipitation in the NAM region.
Variation in pediatric outpatient adenotonsillectomy costs in a multihospital network
Authors: Meier Jeremy D. , Zhang Yingying , Greene Tom H. , Curtis Jonathan L. , Srivastava Rajendu
Published: November 2014

Objectives/Hypothesis

Identify hospital costs for same‐day pediatric adenotonsillectomy (T&A) surgery, and evaluate surgeon, hospital, and patient factors influencing variation in costs, and compare relationship of costs to complications for T&A.

Study Design

Observational retrospective cohort study.

Methods

A multihospital network's standardized activity‐based accounting system was used to determine hospital costs per T&A from 1998 to 2012. Children 1 to 18 years old who underwent same‐day T&A surgery were included. Subjects with additional procedures were excluded. Mixed effects analyses were performed to identify variation in mean costs due to surgeon, hospital, and patient factors. Surgeons' mean cost/case was related to subsequent complications, defined as any unplanned visit within 21 days in the healthcare system.

Results

The study cohort included 26,626 T&As performed by 66 surgeons at 18 hospitals. Mean cost per T&A was $1,355 ± $505. Mixed effects analysis using patient factors as fixed effects and surgeon and hospital as a random effect identified significant variation in mean costs per surgeon, with 95% of surgeons having a mean cost/case between 67% and 150% of the overall mean (range, $874–$2,232/case). Similar variability was found among hospitals, with 95% of the facilities having mean costs between 64% to 156% of the mean (range, $1,029–$2,385/case). Severity of illness and several other patient factors exhibited small but statistically significant associations with cost. Surgeons' mean cost/case was moderately associated with an increased complication rate.

Conclusions

Significant variation in same‐day pediatric T&A surgery costs exists among different surgeons and hospitals within a multihospital network. Reducing variation in costs while maintaining outcomes may improve healthcare value and eliminate waste.

Level of Evidence

4. Laryngoscope, 125:1215–1220, 2015
The national cost burden of bronchial foreign body aspiration in children
Authors: Kim Irene A. , Shapiro Nina , Bhattacharyya Neil
Published: November 2014

Objectives/Hypothesis

Foreign body aspiration (FBA) continues to be a concerning pediatric problem, accounting for thousands of emergency room visits and more than 100 deaths each year in the United States. The costs incurred with hospitalizations and procedures following these events are the focus of this study.

Study Design

Retrospective review.

Methods

The Nationwide Inpatient Sample from 2009 to 2011 was analyzed, and all cases with pediatric bronchial foreign body aspirations (International Classification of Diseases‐9 codes: 934.0, 934.1, 934.8, and 934.9) were reviewed. Cases were analyzed to determine type of foreign body aspiration, procedural interventions performed, duration of inpatient stay, mortality rate, complications, and posthospitalization disposition. The median length of hospital stay and total costs associated with aspiration events were determined.

Results

An estimated 1,908 ± 273 pediatric bronchial FBA patients were admitted annually over the 3‐year period (mean age, 3.6 ± 0.3 years; 61.3% ± 1.9% male). The ratio of foreign object aspiration to food aspiration was 5:3. Overall, 56%.0 ± 3.6% of the patients underwent a bronchoscopic procedure for foreign body removal; of those, 41.5% ± 2.5% had a foreign body removed at the time of the endoscopy. The hospital mortality rate associated with bronchial aspiration was 1.8% ± 0.4%; and 2.2% ± 0.5% of patients were diagnosed with anoxic brain injury. The median length of stay was 3 days (25th–75th interquartile range, 1–7 days).The median charges and actual costs per case were $20,820 ($10,800–$53,453) and $6,720 ($3,628–$16,723), respectively.

Conclusion

The annual overall inpatient cost associated with pediatric bronchial foreign‐body aspiration is approximately $12.8 million. Combined, the rate of death or anoxic brain injury associated with pediatric foreign body is approximately 4%.

Level of Evidence

2C. Laryngoscope, 125:1221–1224, 2015
Management of intractable Ménière's disease after intratympanic injection of Gentamicin
Authors: Rah Yoon C. , Han Jae J. , Park Jaehong , Choi Byung Y. , Koo Ja‐Won
Published: November 2014

Objectives/Hypothesis

1) To evaluate the efficacy of, and problems with, intratympanic gentamicin injection (ITG) in medically intractable definite Ménière's disease (MD) and secondary endolymphatic hydrops (EH); and 2) to review the vestibular status and treatment options of intractable vertigo even after ITG.

Study Design

Retrospective case review and survey.

Methods

780 patients with definite MD and secondary EH were enrolled. Long‐term outcomes and problems of applied treatment options including ITG and exploratory tympanotomy and gentamicin application (ETG) were analyzed.

Results

Of the 780 patients, 95 patients received ITG. Class A and B control of vertigo was achieved in 85 (89.5%) patients; two patients were class C and eight patients were class F (ETG: 6; labyrinthectomy: 1; vestibular neurectomy: 1). Among seven patients who received ETG including 1 patient who skipped ITG due to chronic otitis media, five patients improved to class A, showing a 71.4% success rate; and labyrinthectomies were performed subsequently in the two remaining patients. Vertigo was controlled (class A) in all the patients who received labyrinthectomies (n = 4) or vestibular neurectomy (n = 1). Eight patients (8.4%) experienced more than 10 dB worsening, and two patients (2.1%) progressed to bilateral Ménière's disease.

Conclusion

ITG failed to control vertigo in 10.5% of cases. ETG may be a reasonable option to facilitate the delivery of gentamicin into the inner ear by direct application of gentamicin over the round window and the oval window. Labyrinthectomy and vestibular neurectomy still have roles in the era of ITG.

Level of Evidence

4. Laryngoscope, 125:972–978, 2015
Novel preparation method for improving the dispersion of ionic liquid‐modified montmorillonite in poly(ethylene terephthalate)
Authors: Majdzadeh‐Ardakani Kazem , Lofgren Elizabeth A. , Jabarin Saleh A.
Published: November 2014

Thermally stable ionic liquids (ILs) were used to modify clay nanoparticles for use in the preparation of poly(ethylene terephthalate)/clay nanocomposites. Nanoclays with smaller particle size distributions were prepared with a two‐step centrifugation method that removed large particles from commercial montmorillonite (MMT). Scanning electron microscopy of aqueous dispersions of MMT and centrifuged clay (CMMT) illustrated that the average particle size of CMMT in water was much lower than that of MMT in water. Both CMMT and MMT were modified with imidazolium‐ and phosphonium‐based ILs. Fourier transform infrared spectroscopy revealed that the surfactants were associated with the clay surface. Thermal gravimetric analysis results indicated that clays modified with thermally stable ILs degraded above 300°C and could survive PET processing temperatures. Transmission electron microscopy for nanocomposites revealed an improvement in the dispersion of centrifuged nanoclays (modified with both imidazolium and phosphonium ILs) into the polymer matrix compared to non‐centrifuged modified MMT with larger particle sizes. X‐ray diffraction and differential scanning calorimetry data indicated that particle size distributions have a significant effect on the dispersion and rate of crystallization of nanoclays modified with imidazolium surfactants. There was, however, a less important effect of centrifugation on the dispersion of nanoclays modified with phosphonium surfactants. POLYM. COMPOS. 37:1259–1266, 2016. © 2014 Society of Plastics Engineers
Continuous observation of particle polymerization by means of light scattering extrapolation method
Authors: Kratochvíl P. , Munk P. , Sedláček B.
Published: November 2014

A method for observation of molecular weight changes and the size of particles by means of the continuous measurement of the angular dependence of the intensity of scattered light is described. This method can be used for a considerable range of molecular weights, and no assumptions concerning the shape of particles need be made. The resulte are usable directly if the interaction constant B = 0; otherwise, these are to be corrected by means of experimentally determined dependence of B on the molecular weight. This method was verified by studying the course of the aggregation of heat‐denatured albumin.
An analysis approach to identify specific functional sites in orthologous proteins using sequence and structural information: Application to neuroserpin reveals regions that differentially regulate inhibitory activity
Authors: Lee Tet Woo , Yang Annie Shu‐Ping , Brittain Thomas , Birch Nigel P.
Published: November 2014

The analysis of sequence conservation is commonly used to predict functionally important sites in proteins. We have developed an approach that first identifies highly conserved sites in a set of orthologous sequences using a weighted substitution‐matrix‐based conservation score and then filters these conserved sites based on the pattern of conservation present in a wider alignment of sequences from the same family and structural information to identify surface‐exposed sites. This allows us to detect specific functional sites in the target protein and exclude regions that are likely to be generally important for the structure or function of the wider protein family. We applied our method to two members of the serpin family of serine protease inhibitors. We first confirmed that our method successfully detected the known heparin binding site in antithrombin while excluding residues known to be generally important in the serpin family. We next applied our sequence analysis approach to neuroserpin and used our results to guide site‐directed polyalanine mutagenesis experiments. The majority of the mutant neuroserpin proteins were found to fold correctly and could still form inhibitory complexes with tissue plasminogen activator (tPA). Kinetic analysis of tPA inhibition, however, revealed altered inhibitory kinetics in several of the mutant proteins, with some mutants showing decreased association with tPA and others showing more rapid dissociation of the covalent complex. Altogether, these results confirm that our sequence analysis approach is a useful tool that can be used to guide mutagenesis experiments for the detection of specific functional sites in proteins. Proteins 2015; 83:135–152. © 2014 Wiley Periodicals, Inc.
Turkish–German Transnational Social Space: Stitching Across Borders
Authors: Bilecen Başak , Çatır Gül , Orhon Aslı
Published: November 2014

This paper examines the social protection strategies of migrants living in Turkish–German transnational social space. Drawing on 20 interviews conducted with migrants in Germany and ten with their significant others in Turkey with a matched sample, we investigate ‘stitching’ strategy, that is, a process by which migrants in the host country continually attach themselves to the society back in their country of origin and, as a result, tap into protective resources in their interpersonal networks. We discuss the significance of high levels of transnationality displayed by our sample in protective resource flows and the ways in which inequalities are created and recreated from the respondents' perspectives. By examining transnationality as a marker of heterogeneity, our study contributes to the literature through an in‐depth analysis of a major strategy for social protection while analysing the meaning of reciprocal relationships. Copyright © 2014 John Wiley & Sons, Ltd.