bluuebunny/crossref_metadata_2025 huggingface dataset:
The poppy seed defense: a novel solution
Authors: Chen P. , Braithwaite R. A. , George C. , Hylands P. J. , Parkin M. C. , Smith N. W. , Kicman A. T.
Published: December 2013

A major toxicological challenge is distinguishing whether morphine in urine, in the absence of 6‐monoacetylmorphine (6‐MAM), originates from ‘street’ heroin use or poppy seed ingestion. Manufacturing byproducts from the synthesis of illicit heroin include those that originate from the reaction of acetic anhydride with the alkaloid impurity, thebaine, which undergoes skeletal rearrangement, resulting in compounds with a 2‐(N‐methylacetamido)ethyl side‐chain. The hypothesis that the tertiary amide in this side‐chain is resistant to endogenous hydrolysis was supported from in‐vitro experiments; a glucuronide metabolite (designated ‘ATM4G’) was identified that may be used as a marker of ‘street’ heroin administration. Liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) analysis for this metabolite was then performed on selected urine specimens from 22 known heroin users, these being negative on routine testing for 6‐MAM by gas chromatography‐mass spectrometry (GC‐MS), using the generally applied reporting threshold of 10 ng/mL, but positive for the presence of morphine. Peaks corresponding to the retention time for the metabolite marker were clearly observed for 16 of the 22 samples, with variations of the ratios of its three dependent ions being within ± 30% of that produced in vitro. Conversely, 6‐MAM was detected in only 3 samples, but at concentrations <1 ng/mL. Such a high frequency for the presence of the metabolite marker in urine, in the absence of 6‐MAM, is noteworthy and suggests that detection of this metabolite may offer an important advance in forensic toxicology, allowing the development of a new and more definitive test for heroin abuse and thus a potential solution to the so‐called ‘poppy seed defense’. Copyright © 2013 John Wiley & Sons, Ltd.
Total Synthesis of Calothrixin B and Its Analogs
Authors: Saravanan Velu , Muthu Ramalingam Bose , Mohanakrishnan Arasambattu K.
Published: December 2013

The total synthesis of calothrixin B and its analogs was achieved starting from 2‐methylindole. The synthesis involved an electrocyclization of 2‐nitroarylvinyl‐3‐phenylsulfonylvinylindoles as a key step to give 2‐nitroaryl‐4‐methoxy‐3‐methylcarbazoles. Oxidation of these compounds followed by reductive cyclization led to N‐phenylsulfonylquinocarbazoles. These quinocarbazoles underwent hydrolysis and aerial oxidation in one pot to give the target compounds.
Direct Access to 4,5‐Disubstituted [2.2]Paracyclophanes by Selective ortho‐Halogenation with Pd‐Catalyzed C–H Activation
Authors: Kramer Joshua J. P. , Yildiz Ceylan , Nieger Martin , Bräse Stefan
Published: December 2013

A palladium‐catalyzed protocol for the halogenation of [2.2]paracyclophanes by C–H activation is described, and ortho selectivity is achieved with an O‐methyloxime directing group. Bromination and iodination of the sterically demanding [2.2]paracyclophane proceed in good yields with inexpensive and readily available N‐halosuccinimides. Deprotection of the O‐methyloximes yields ortho‐halogenated aldehydes as attractive intermediates for the modular synthesis of 4,5‐disubstituted [2.2]paracyclophanes. The synthetic value of this protocol was demonstrated by exemplary conversions of the carbaldehyde and halogen site. Additionally, early stage resolution and subsequent bromination/deprotection provides the brominated aldehyde in enantiopure form.
Molecular Mechanistic Explanation for the Spectrum of Cholestatic Disease Caused by the S320F Variant of ABCB4
Authors: Andress Edward J. , Nicolaou Michael , Romero Marta R. , Naik Sandhia , Dixon Peter H. , Williamson Catherine , Linton Kenneth J.
Published: December 2013

ABCB4 flops phosphatidylcholine into the bile canaliculus to protect the biliary tree from the detergent activity of bile salts. Homozygous-null

ABCB4

mutations cause the childhood liver disease, progressive familial intrahepatic cholestasis, but cause and effect is less clear, with many missense mutations linked to less severe cholestatic diseases. ABCB4S320F, in particular, is described in 13 patients, including in heterozygosity with ABCB4A286V, ABCB4A953D, and null mutants, whose symptoms cover the spectrum of cholestatic disease. We sought to define the impact of these mutations on the floppase, explain the link with multiple conditions at the molecular level, and investigate the potential for reversal. ABCB4S320F, ABCB4A286V, and ABCB4A953D expression was engineered in naïve cultured cells. Floppase expression, localization, and activity were measured by western blot, confocal microscopy, and lipid transport assays, respectively. ABCB4S320F was fully active for floppase activity but expression at the plasma membrane was reduced to 50%. ABCB4A286V expressed and trafficked efficiently but could not flop lipid, and ABCB4A953D expressed poorly and was impaired in floppase activity. Proteasome inhibition stabilized nascent ABCB4S320F and ABCB4A953D but did not improve plasma membrane localization. Cyclosporin-A improved plasma membrane localization of both ABCB4S320F and ABCB4A953D, but inhibited floppase activity.

Conclusion :

The level of ABCB4 functionality correlates with, and is the primary determinant of, cholestatic disease severity in these patients. ABCB4S320F homozygosity, with half the normal level of ABCB4, is the tipping point between more benign and potentially fatal cholestasis and makes these patients more acutely sensitive to environmental effects. Cyclosporin-A increased expression of ABCB4S320F and ABCB4A953D, suggesting that chemical chaperones could be exploited for therapeutic benefit to usher in a new era of personalized medicine for patients with ABCB4-dependent cholestatic disease. (Hepatology 2014;59:1921–1931)
SIRT1 Controls Liver Regeneration by Regulating Bile Acid Metabolism Through Farnesoid X Receptor and Mammalian Target of Rapamycin Signaling
Authors: García-Rodríguez Juan L. , Barbier-Torres Lucía , Fernández-Álvarez Sara , Gutiérrez-de Juan Virginia , Monte María J. , Halilbasic Emina , Herranz Daniel , Álvarez Luis , Aspichueta Patricia , Marín Jose J.G. , Trauner Michael , Mato Jose M. , Serrano Manuel , Beraza Naiara , Martínez-Chantar María Luz
Published: December 2013

Sirtuin1 (SIRT1) regulates central metabolic functions such as lipogenesis, protein synthesis, gluconeogenesis, and bile acid (BA) homeostasis through deacetylation. Here we describe that SIRT1 tightly controls the regenerative response of the liver. We performed partial hepatectomy (PH) to transgenic mice that overexpress SIRT1 (SIRT). SIRT mice showed increased mortality, impaired hepatocyte proliferation, BA accumulation, and profuse liver injury after surgery. The damaging phenotype in SIRT mice correlated with impaired farnesoid X receptor (FXR) activity due to persistent deacetylation and lower protein expression that led to decreased FXR-target gene expression; small heterodimer partner (SHP), bile salt export pump (BSEP), and increased Cyp7A1. Next, we show that 24-norUrsodeoxycholic acid (NorUDCA) attenuates SIRT protein expression, increases the acetylation of FXR and neighboring histones, restores trimethylation of H3K4 and H3K9, and increases miR34a expression, thus reestablishing BA homeostasis. Consequently, NorUDCA restored liver regeneration in SIRT mice, which showed increased survival and hepatocyte proliferation. Furthermore, a leucine-enriched diet restored mammalian target of rapamycin (mTOR) activation, acetylation of FXR and histones, leading to an overall lower BA production through SHP-inhibition of Cyp7A1 and higher transport (BSEP) and detoxification (Sult2a1) leading to an improved liver regeneration. Finally, we found that human hepatocellular carcinoma (HCC) samples have increased presence of SIRT1, which correlated with the absence of FXR, suggesting its oncogenic potential.

Conclusion :

We define SIRT1 as a key regulator of the regenerative response in the liver through posttranscriptional modifications that regulate the activity of FXR, histones, and mTOR. Moreover, our data suggest that SIRT1 contributes to liver tumorigenesis through dysregulation of BA homeostasis by persistent FXR deacetylation. (Hepatology 2014;59:1972–1983)
Hippocampal spatial mapping and the acquisition of competing responses
Authors: Skinner Darlene M. , Martin Gerard M. , Wright Sandra L. , Tomlin Julian , Odintsova Irina V. , Thorpe Christina M. , Harley Carolyn W. , Marrone Diano F.
Published: December 2013

Response reversal learning is facilitated in many species, including humans, when competing responses occur in separate contexts. This suggests hippocampal maps may facilitate the acquisition of competing responses and is consistent with the hypothesis that contextual encoding permits rapid acquisition of new behaviors in similar environments. To test this hypothesis, the pattern of Arc expression was examined after rats completed a series of left/right response reversals in a T‐maze. This reversal training occurred in the same room, two different rooms, or within a single room but with the maze enclosed in wall‐length curtains of different configurations (i.e., black/white square or circle). Across CA1 and CA3, successive T‐maze exposures in the same room recruited the same cells to repeatedly transcribe Arc, while a unique population of cells transcribed Arc in response to each of two different rooms as well as to the two unique curtain configurations in the same room. The interference from original learning that was evident on the first reversal in animals without a context switch was absent in groups that experienced changes in room or curtain configuration. However, only the use of unique rooms, and not changes in the curtained enclosure, facilitated learning across response reversals relative to the groups exposed to only one room. Thus, separate hippocampal maps appear to provide protection from the original learning interference but do not support improved reversals over trials. The present data suggest changes in heading direction input, rather than remapping, are the source of facilitation of reversal learning. © 2013 Wiley Periodicals, Inc.
Regional vulnerability of hippocampal subfields to aging measured by structural and diffusion MRI
Authors: Pereira Joana B. , Valls‐Pedret Cinta , Ros Emilio , Palacios Eva , Falcón Carles , Bargalló Nuria , Bartrés‐Faz David , Wahlund Lars‐Olof , Westman Eric , Junque Carme
Published: December 2013

In the past few years, there has been an increasing awareness of the regional vulnerability of the hippocampus to age‐related processes. However, to date, no studies have assessed the effects of age on different structural magnetic resonance parameters in the specific hippocampal subfields. In this study, we measured volume, mean diffusivity (MD) and fractional anisotropy (FA) in the presubiculum, subiculum, fimbria, cornu ammonis (CA) 1,2‐3,4‐DG and the whole hippocampus in fifty cognitively intact elder adults between 50 and 75 years of age (20 men, 30 women). Segmentation of hippocampal subfields was performed using FreeSurfer. Individual MD and FA images were coregistered to T1‐weighted volumes using FLIRT of FSL. Linear regression analyses were performed to assess the effects of age on the anatomical measures of each subfield. In addition, multiple regression analyses were also carried out to assess which of the anatomical measures that showed a correlation with age in the previous analyses, were the best age predictors in the hippocampus. In agreement with previous studies, our results showed a significant association between age and volume (P < 0.001) as well as MD (P < 0.001) in the whole hippocampus. Regarding the specific hippocampal subfields, we found that age had a significant negative effect on volume in CA2‐3 (P < 0.001) and CA4‐DG (P < 0.001). Importantly, we found a positive effect of age on MD in CA2‐3 (P < 0.001) and fimbria (P < 0.001) as well as a negative age effect on FA in the subiculum (P < 0.001). Multiple regression analyses revealed that the best overall predictors of age in the hippocampus were MD in the fimbria and volume of CA2‐3, which explained 73.8% of the age variance. These results indicate that age has an effect both on volume and diffusion tensor imaging measures in different subfields, suggesting they provide complementary information on age‐related processes in the hippocampus. © 2013 Wiley Periodicals, Inc.
Phenotype of mice with inducible ablation of GluA1 AMPA receptors during late adolescence: Relevance for mental disorders
Authors: Inta Dragos , Vogt Miriam A. , Elkin Hasan , Weber Tillmann , Lima‐Ojeda Juan M. , Schneider Miriam , Luoni Alessia , Riva Marco A. , Gertz Karen , Hellmann‐Regen Julian , Kronenberg Golo , Meyer‐Lindenberg Andreas , Sprengel Rolf , Gass Peter
Published: December 2013

Adolescence is characterized by important molecular and anatomical changes with relevance for the maturation of brain circuitry and cognitive function. This time period is of critical importance in the emergence of several neuropsychiatric disorders accompanied by cognitive impairment, such as affective disorders and schizophrenia. The molecular mechanisms underlying these changes at neuronal level during this specific developmental stage remains however poorly understood. GluA1‐containing AMPA receptors, which are located predominantly on hippocampal neurons, are the primary molecular determinants of synaptic plasticity. We investigated here the consequences of the inducible deletion of GluA1 AMPA receptors in glutamatergic neurons during late adolescence. We generated mutant mice with a tamoxifen‐inducible deletion of GluA1 under the control of the CamKII promoter for temporally and spatially restricted gene manipulation. GluA1 ablation during late adolescence induced cognitive impairments, but also marked hyperlocomotion and sensorimotor gating deficits. Unlike the global genetic deletion of GluA1, inducible GluA1 ablation during late adolescence resulted in normal sociability. Deletion of GluA1 induced redistribution of GluA2 subunits, suggesting AMPA receptor trafficking deficits. Mutant animals showed increased hippocampal NMDA receptor expression and no change in striatal dopamine concentration. Our data provide new insight into the role of deficient AMPA receptors specifically during late adolescence in inducing several cognitive and behavioral alterations with possible relevance for neuropsychiatric disorders. © 2013 Wiley Periodicals, Inc.
The Co‐Occurring Development of Executive Function Skills and Receptive Vocabulary in Preschool‐Aged Children: A Look at the Direction of the Developmental Pathways
Authors: Weiland Christina , Barata M. Clara , Yoshikawa Hirokazu
Published: December 2013

Despite consensus in the developmental literature regarding the role of executive function (EF) skills in supporting the development of language skills during the preschool years, we know relatively little about the associations between EF skills, including all EF components, and vocabulary skills among preschool‐aged children. In this paper, we address this gap by fitting structural equation models to examine the associations between beginning‐of‐preschool EF and end‐of‐preschool receptive vocabulary, as well as the association between beginning‐of‐preschool receptive vocabulary and end‐of‐preschool EF skills, to data from 400 preschool‐aged children. We find that EF skills at the beginning of preschool are a significant predictor of receptive vocabulary skills at the end of preschool, controlling for receptive vocabulary at the beginning of preschool. However, receptive vocabulary skills at the beginning of preschool do not predict EF skills at the end of preschool, controlling for EF at the beginning of preschool. Our findings are suggestive of the important role EF plays in supporting growth in receptive vocabulary skills, above and beyond earlier vocabulary levels, and of the direction of the developmental pathway between EF and receptive vocabulary in the preschool years. The discussion highlights the need for further research in the optimal approach for supporting children's EF skill development in preschool. Copyright © 2013 John Wiley & Sons, Ltd.
Treatment of single peripheral pulmonary emboli: Patient outcomes and factors associated with decision to treat
Authors: Green O'Neil , Lempel Jason , Kolodziej Andrew , Sandhu Rabinder , Castro‐Pereira Daniel , Wang Yun , Lee Ronald , Fine Jonathan M.
Published: December 2013

BACKGROUND

Increasing use of computed tomography pulmonary angiography together with higher‐resolution scanners has increased the detection of peripheral filling defects. Physicians face the dilemma of whether to treat patients with these findings, especially single defects. The aims of this study were to compare the outcomes of treated and untreated patients with single peripheral filling defects (SPFD) and identify factors associated with treatment.

METHODS

All cases with SPFDs over 66 months in a single institution were identified. Patient and treatment information were abstracted and data on 90‐day mortality and postdischarge venous thromboembolism (VTE) were collected.

RESULTS

A total of 4906 computed tomography pulmonary angiograms were reviewed. A SPFD was identified in 3.1% (n = 153). Of the 153 patients, 134 met criteria for study inclusion. In 99 of 134 (73.9%) studies, the defect was called a pulmonary embolus (PE) by the initial radiologist. Treatment was administered to 61 of 134 (45.5%) patients; 5 patients died in each group. Postdischarge VTE occurred in 3 treated and 2 untreated patients. In 52 of 153 cases, an additional study was performed. None of the patients with normal ventilation perfusion scan and compression ultrasound received treatment. Immobility (odds ratio [OR]: 3.90, 95% confidence interval [CI]: 1.45‐10.60), previous VTE (OR: 3.72, 95% CI: 1.18‐11.70), and determination of PE by the radiologist (OR: 24.68, 95% CI: 5.40–112.90) were associated with treatment.

CONCLUSIONS

There was no difference in 90‐day mortality or recurrence between treated and untreated patients. The most influential factor associated with treatment was the radiologist's interpretation. When secondary lung imaging studies were negative, no patient received treatment. Journal of Hospital Medicine 2014;9:42–47. © 2013 Society of Hospital Medicine
On‐line process monitoring of coffee roasting by resonant laser ionisation time‐of‐flight mass spectrometry: bridging the gap from industrial batch roasting to flavour formation inside an individual coffee bean
Authors: Hertz‐Schünemann R. , Dorfner R. , Yeretzian C. , Streibel T. , Zimmermann R.
Published: December 2013

Resonance‐enhanced multiphoton ionisation time‐of‐flight mass spectrometry (REMPI‐TOFMS) enables the fast and sensitive on‐line monitoring of volatile organic compounds (VOC) formed during coffee roasting. On the one hand, REMPI‐TOFMS was applied to monitor roasting gases of an industrial roaster (1500 kg/h capacity), with the aim of determining the roast degree in real‐time from the transient chemical signature of VOCs. On the other hand, a previously developed μ‐probe sampling device was used to analyse roasting gases from individual coffee beans. The aim was to explore fundamental processes at the individual bean level and link these to phenomena at the batch level. The pioneering single‐bean experiments were conducted in two configurations: (1) VOCs formed inside a bean were sampled in situ, i.e. via a drilled μ‐hole, from the interior, using a μ‐probe (inside). (2) VOCs were sampled on‐line in close vicinity of a single coffee bean's surface (outside). The focus was on VOCs originating from hydrolysis and pyrolytic degradation of chlorogenic acids, like feruloyl quinic acid and caffeoyl quinic acid. The single bean experiments revealed interesting phenomena. First, differences in time–intensity profiles between inside versus outside (time shift of maximum) were observed and tentatively linked to the permeability of the bean's cell walls material. Second, sharp bursts of some VOCs were observed, while others did exhibit smooth release curves. It is believed that these reflect a direct observation of bean popping during roasting. Finally, discrimination between Coffea arabica and Coffea canephora was demonstrated based on high‐mass volatile markers, exclusively present in spectra of Coffea arabica. Copyright © 2013 John Wiley & Sons, Ltd.
A PROSPECTIVE STUDY: INFLAMMATION, INFECTION AND COMORBIDITY IN PATIENTS ON LONG‐TERM DIALYSIS
Authors: Akbaş Türkay , Mülazımoğlu Lütfiye , Aksu Burak , Akoğlu Emel
Published: December 2013

Background

The goal of this study was to identify inflammatory and infectious markers and their roles in mortality.

Methods

We enrolled 111 patients on haemodialysis (HD) and collected data at three time points (baseline, 33 and 76 months).

Results

Rates of Chlamydophila pneumoniae IgG, CRP ≥3 mg/l, ESR >50 mm/hour and fibrinogen >4 g/l were, respectively, 63.1%, 60.4%, 48.6% and 42.3%. Mortality was 21.6% and 43.2% at 33 and 76 months where 58.3% of all deaths were cardiocerebrovascular (CCV) related. Non‐survivors were older than survivors. Univariate analysis showed diabetes mellitus (DM) and cerebrovascular accident (CVA) as important for the 33‐month all‐cause mortality, and CRPlog, fibrinogen, ESR >50 mm/hour, cardiovascular disease (CVD) and DM for the 76‐month all‐cause mortality. CVA was meaningful for the 33‐month CCV mortality, and CVD, DM and ESR >50 mm/hour for the 76‐month CCV mortality. Kaplan–Meier revealed poorer survival for patients with ESR >50 mm/hour at 76 months. Cox regression showed CVD, CVA and age as mortality predictors.

Conclusion

Age, CVD and CVA are predictors for mortality in patients on HD patients, but the presence of C. pneumoniae IgG and inflammation are not.
T4a laryngeal cancer survival: Retrospective institutional analysis and systematic review
Authors: Francis Evana , Matar Nayla , Khoueir Nadim , Nassif Charbel , Farah Chadi , Haddad Amine
Published: December 2013

Objectives/Hypothesis

To assess the survival outcomes of a homogeneous group of pT4a laryngeal cancer patients treated at our institution by primary total laryngectomy and neck dissection with adjuvant therapy when indicated, and to systematically review studies reporting overall survival outcomes in T4a laryngeal cancer.

Study Design

Systematic review of PubMed and Embase databases.

Methods

Records of 108 laryngeal cancer patients treated by total laryngectomy were reviewed. pT4a cases treated by primary total laryngectomy between 1998 and 2010 were included. Overall and disease‐free survival at 2 and 5 years were reported. A systematic review was performed including all published studies reporting overall survival outcomes by treatment modality in T4 laryngeal cancer patients.

Results

Thirty cases met the inclusion criteria. At 2 years, overall and disease‐free survival were 81.3% and 78%, respectively. The 5‐year overall and disease‐free survival rates were 60%. The systematic review retrieved 24 articles. Overall survival at 2 years ranged from 12% to 21.2% with radiotherapy, <30% to 65% with chemoradiotherapy, and from 30% to 100% with surgery. At 5 years, it ranged from 0% to 75% with radiotherapy, 16% to 50.4% with chemoradiotherapy, and 10% to 80.9% with surgery.

Conclusions

Primary total laryngectomy provides a high survival rate for pT4a laryngeal cancer patients. Randomized controlled trials including homogenous patients are still needed before shifting to organ preservation protocols in these patients.

Level of Evidence

NA Laryngoscope, 124:1618–1623, 2014
Ten years of proteomics in multiple sclerosis
Authors: Farias Alessandro S. , Pradella Fernando , Schmitt Andrea , Santos Leonilda M. B. , Martins‐de‐Souza Daniel
Published: December 2013

Multiple sclerosis, which is the most common cause of chronic neurological disability in young adults, is an inflammatory, demyelinating, and neurodegenerative disease of the CNS, which leads to the formation of multiple foci of demyelinated lesions in the white matter. The diagnosis is based currently on magnetic resonance image and evidence of dissemination in time and space. However, this could be facilitated if biomarkers were available to rule out other disorders with similar symptoms as well as to avoid cerebrospinal fluid analysis, which requires an invasive collection. Additionally, the molecular mechanisms of the disease are not completely elucidated, especially those related to the neurodegenerative aspects of the disease. The identification of biomarker candidates and molecular mechanisms of multiple sclerosis may be approached by proteomics. In the last 10 years, proteomic techniques have been applied in different biological samples (CNS tissue, cerebrospinal fluid, and blood) from multiple sclerosis patients and in its experimental model. In this review, we summarize these data, presenting their value to the current knowledge of the disease mechanisms, as well as their importance in identifying biomarkers or treatment targets.
Spin pumping through quantum dots
Authors: Rojek Stephan , Governale Michele , König Jürgen
Published: December 2013

We propose schemes for generating spin currents into a semiconductor by adiabatic or non‐adiabatic pumping of electrons through interacting quantum dots. The appeal of such schemes lies in the possibility to tune the pumping characteristics via gate voltages that control the properties of the quantum dot. The calculations are based on a systematic perturbation expansion in the tunnel‐coupling strength and the pumping frequency, expressed within a diagrammatic real‐time technique. Special focus is put on the possibility of pure spin pumping, i.e., of pumping spin currents without charge currents.

Setup of a device for generating a spin current into a semiconductor by adiabatic or non‐adiabatic pumping of electrons through an interacting quantum dot.
Trametenolic Acid B Reverses Multidrug Resistance in Breast Cancer Cells Through Regulating the Expression Level of P‐Glycoprotein
Authors: Zhang Qiaoyin , Wang Junzhi , He Haibo , Liu Hongbing , Yan Ximing , Zou Kun
Published: December 2013

Trametenolic acid B (TAB) is the main active composition of Trametes lactinea (Berk.) Pat which possesses anti‐tumor activities. There was no report its antitumor effect through regulating P‐glycoprotein (P‐gp) so far, due to P‐gp over expression is one of the most important mechanisms contributing to the multiple drug resistance phenotype. The present aim was to investigate the effects of TAB on P‐gp in multidrug‐resistant cells; Paclitaxel‐resistant cell line MDA‐MB‐231/Taxol was established by stepwise exposure for 10 months. MDA‐MB‐231 cells and MDA‐MB‐231/Taxol cells were treated with TAB, and their growth was evaluated using MTT assays. Paclitaxel accumulation in the cells was analyzed by high performance liquid chromatogram (HPLC). The activity of P‐gp was detected by intracellular accumulation of rhodamine123 (Rho123), and the protein expression of P‐gp was evaluated using western blot. Results indicated that the IC50 of MDA‐MB‐231/Taxol to paclitaxel (Taxol) was 33 times higher than that of nature MDA‐MB‐231. TAB increased the intracellular concentration of Taxol and inhibited the activity of P‐gp and suppressed the expression of P‐gp in MDA‐MB‐231/Taxol cells. Our present results showed that TAB could reverse Taxol resistance in MDA‐MB‐231/Taxol cells, mainly inhibiting the activity of P‐gp and down‐regulating the expression level of P‐gp, and then enhancing the accumulation of chemotherapy agents. © 2013 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.
Apoptosis Induction by 13‐Acetoxyrolandrolide through the Mitochondrial Intrinsic Pathway
Authors: Acuña Ulyana Muñoz , Matthew Susan , Pan Li , Kinghorn A. Douglas , Swanson Steven M. , Carcache de Blanco Esperanza J
Published: December 2013

The aim of this study was to evaluate the mechanisms of cytotoxicity of the sesquiterpene lactone 13‐acetoxyrolandrolide, a nuclear factor kappa B (NF‐κB) inhibitor that was previously isolated from Rolandra fruticosa. The effects associated with the inhibition of the NF‐κB pathway included dose‐dependent inhibition of the NF‐κB subunit p65 (RelA) and inhibition of upstream mediators IKKβ and oncogenic Kirsten rat sarcoma (K‐Ras). The inhibitory concentration of 13‐acetoxyrolandrolide on K‐Ras was 7.7 µm. The downstream effects of the inhibition of NF‐κB activation were also investigated in vitro. After 24 h of treatment with 13‐acetoxyrolandrolide, the mitochondrial transmembrane potential was depolarized in human colon cancer (HT‐29) cells. The mitochondrial oxidative phosphorylation was also negatively affected, and reduced levels of nicotinamine adenine dinucleotide phosphate (NAD(P)H) were detected after 2 h of 13‐acetoxyrolandrolide exposure. Furthermore, the expression of the pro‐apoptotic protein caspase‐3 increased in a concentration‐dependent manner. Cell flow cytometry showed that 13‐acetoxyrolandrolide induced cell cycle arrest at G1, indicating that the treated cells had undergone caspase‐3‐mediated apoptosis, indicating negative effects on cancer cell proliferation. These results suggest that 13‐acetoxyrolandrolide inhibits NF‐κB and K‐Ras and promotes cell death mediated through the mitochondrial apoptotic pathway. Copyright © 2013 John Wiley & Sons, Ltd.
Tractable stability analysis for systems containing repeated scalar slope‐restricted nonlinearities
Authors: Turner Matthew C. , Kerr Murray L. , Sofrony Jorge
Published: December 2013

This paper proposes an LMI‐based approach for studying the stability of feedback interconnections of a finite dimensional LTI system and a nonlinear element that consists of several identical scalar nonlinearities that have restrictions on their sector and slope. The results are based on the integral quadratic constraint stability analysis framework and other recent results that give a sharp characterisation of stability multipliers for monotone, repeated scalar nonlinearities. Several examples show the effectiveness of the proposed approach; the lack of conservatism in the results is noteworthy. Copyright © 2013 John Wiley & Sons, Ltd.
Advanced Age Remains an Achilles Heel for Liver Resections
Authors: Sulpice Laurent , Rayar Michel , Campillo Boris , Pery Claire , Guillaud Antoine , Meunier Bernard , Boudjema Karim
Published: December 2013

Background

As the general population is aging, surgery in elderly patients has become a major public health issue. This basic question is especially true for liver resection (LR). The aim of this study was to evaluate the operative risks of LR in the elderly.

Methods

Retrospective analysis of a large recent and monocentric database of LR was performed between January 1, 2005 and May 31, 2011. Patients were categorized into three groups (<60, 60–74, and ≥75 years old) to analyze postoperative outcomes and 1‐year mortality. Clinicopathologic factors likely to influence outcomes were assessed by univariate and multivariate analysis.

Results

Altogether, 1,001 consecutive LRs were performed in 912 patients (mean age 62 ± 13 years). The distribution of the LR by age was 372 (37.2 %), 477 (47.6 %), and 152 (15.2 %) in patients <60, 60–74, and ≥75 years, respectively. The overall morbidity and mortality rates were 33.3 and 2.5 %, respectively. Age ≥75 years was independently associated with postoperative mortality [odds ratio (OR) 4.75, 95 % confidence interval (CI) 1.5–15.1; p = 0.008] and 1‐year mortality (OR 2.8, 95 % CI 1.2–6.6; p = 0.015). The postoperative complication rate (p = 0.216) was not increased, even for major complications (p = 0.09). The other independent risk factors for mortality were a cirrhotic liver (p = 0.017), preoperative arterial chemoembolization (p = 0.001), caval vein clamping (p = 0.001), and intraoperative blood transfusion (p = 0.044).

Conclusions

Age beyond 75 years represent a risk factor of death after LR and should be avoided after chemoembolization or in cirrhotic patients. A specific assessment using geriatric indexes might be the key to success in this population.
A Note on Statistical Hypothesis Testing Based on Log Transformation of the Mantel–Haenszel Common Odds Ratio for Differential Item Functioning Classification
Authors: Paek Insu , Holland Paul
Published: December 2013

When differential item functioning (DIF) is investigated, DIF classification is made using statistical test results and estimated DIF sizes in practice. One of the well-known DIF classifications is that of the Educational Testing Service (ETS) A (negligible DIF), B (medium DIF), and C (large DIF) rules. This article provides a clarifying note on (a) a sketch of the proof of the asymptotic normality of what is known as the Mantel–Haenszel (MH) delta, which provides the basis of a point and an interval null hypothesis test based on the MH delta, and (b) how to conduct an interval null hypothesis test using the MH delta, which is necessary for the C DIF classification.
Ionenkanäle – Einführung aus physiologischer Perspektive
Authors: Roeper J.
Published: December 2013

Ionenkanäle bilden eine vielfältige Klasse von Transportmembranproteinen. Sie können nach Selektivität der Ionenspezies und der Kontrolle ihres Schaltverhaltens z. B. durch Membranpotenzial oder Bindung von Liganden klassifiziert werden. Der Transport durch Kanalproteine besitzt sowohl eine elektrische wie eine chemische Dimension. Die mit dem selektiven Ionentransport über Membranen einhergehende Ladungstrennung bewirkt eine Veränderung des Membranpotenzials, der Ionenfluss führt parallel zu einer Veränderung von Ionenkonzentrationen. Basierend auf dieser elektrochemischen Doppelnatur der Ionenkanäle lassen sich aus physiologischer Perspektive 2 Funktionsbereiche differenzieren. In erregbaren Zellen steht die Steuerung des Membranpotenzials zur Erzeugung schneller elektrischer Signale im Vordergrund, während gerichteter Ionentransport bei Transportepithelien die zentrale Größe darstellt. So stehen bei einzelnen Ionenkanalkrankheiten meist Erregungs – oder Transportstörungen im Vordergrund.
Money, moral transgressions, and blame
Authors: Xie Wenwen , Yu Boya , Zhou Xinyue , Sedikides Constantine , Vohs Kathleen D.
Published: December 2013

Two experiments tested participants' attributions for others' immoral behaviors when conducted for more versus less money. We hypothesized and found that observers would blame wrongdoers more when seeing a transgression enacted for little rather than a lot of money, and that this would be evident in observers' hand‐washing behavior. Experiment 1 used a cognitive dissonance paradigm. Participants (N = 160) observed a confederate lie in exchange for either a relatively large or a small monetary payment. Participants blamed the liar more in the small (versus large) money condition. Participants (N = 184) in Experiment 2 saw images of someone knocking over another to obtain a small, medium, or large monetary sum. In the small (versus large) money condition, participants blamed the perpetrator (money) more. Hence, participants assigned less blame to moral wrong‐doers, if the latter enacted their deed to obtain relatively large sums of money. Small amounts of money accentuate the immorality of others' transgressions.
Assessment of small fibers using evoked potentials
Authors: Madsen Caspar Skau , Finnerup Nanna Brix , Baumgärtner Ulf
Published: December 2013

Background and purpose

Conventional neurophysiological techniques do not assess the function of nociceptive pathways and are inadequate to detect abnormalities in patients with small-fiber damage. This overview aims to give an update on the methods and techniques used to assess small fiber (Aδ- and C-fibers) function using evoked potentials in research and clinical settings.

Methods

Noxious radiant or contact heat allows the recording of heat-evoked brain potentials commonly referred to as laser evoked potentials (LEPs) and contact heat-evoked potentials (CHEPs). Both methods reliably assess the loss of Aδ-fiber function by means of reduced amplitude and increased latency of late responses, whereas other methods have been developed to record ultra-late C-fiber-related potentials. Methodological considerations with the use of LEPs and CHEPs include fixed versus variable stimulation site, application pressure, and attentional factors. While the amplitude of LEPs and CHEPs often correlates with the reported intensity of the stimulation, these factors may also be dissociated. It is suggested that the magnitude of the response may be related to the saliency of the noxious stimulus (the ability of the stimulus to stand out from the background) rather than the pain perception.

Results

LEPs and CHEPs are increasingly used as objective laboratory tests to assess the pathways mediating thermal pain, but new methods have recently been developed to evaluate other small-fiber pathways. Pain-related electrically evoked potentials with a low-intensity electrical simulation have been proposed as an alternative method to selectively activate Aδ-nociceptors. A new technique using a flat tip mechanical stimulator has been shown to elicit brain potentials following activation of Type I A mechano-heat (AMH) fibers. These pinprick-evoked potentials (PEP) have a morphology resembling those of heat-evoked potentials following activation of Type II AMH fibers, but with a shorter latency. Cool-evoked potentials can be used for recording the non-nociceptive pathways for cooling. At present, the use of cool-evoked potentials is still in the experimental state. Contact thermodes designed to generate steep heat ramps may be programmed differently to generate cool ramps from a baseline of 35◦C down to 32◦C or 30◦C. Small-fiber evoked potentials are valuable tools for assessment of small-fiber function in sensory neuropathy, central nervous system lesion, and for the diagnosis of neuropathic pain. Recent studies suggest that both CHEPs and pinprick-evoked potentials may also be convenient tools to assess sensitization of the nociceptive system.

Conclusions

In future studies, small-fiber evoked potentials may also be used in studies that aim to understand pain mechanisms including different neuropathic pain phenotypes, such as cold- or touch-evoked allodynia, and to identify predictors of response to pharmacological pain treatment.

Implications

Future studies are needed for some of the newly developed methods.
Room temperature decarboxylative trifluoromethylation of α,β-unsaturated carboxylic acids by photoredox catalysis
Authors: Xu Pan , Abdukader Ablimit , Hu Kaidong , Cheng Yixiang , Zhu Chengjian
Published: December 2013

A visible-light-induced decarboxylative trifluoromethylation of α,β-unsaturated carboxylic acids, which uses the Togni reagent as the CF3 source is disclosed.
Synthon transferability probed with IR spectroscopy: cytosine salts as models for salts of lamivudine
Authors: Chakraborty Shaunak , Ganguly Somnath , Desiraju Gautam R.
Published: December 2013

Co-crystal screening of the anti-HIV drug lamivudine was carried out with dicarboxylic acids as co-formers. Salts of cytosine, a molecule that incorporates critical structural features of lamivudine, with the same co-formers, were taken as model systems for IR spectroscopic studies of the synthons in the salts of lamivudine.
Halogen bonding directed supramolecular assembly in bromo-substituted trezimides and tennimides
Authors: Mocilac Pavle , Gallagher John F.
Published: December 2013

The imide-based trezimide and tennimide macrocycle crystal structures typically aggregate as 1-D chains through C–Br⋯OC/N/π(arene) halogen bonds (withNc≤ 0.90) that dominate the solid-state aggregation process in the absence of classical strong hydrogen bond donors.
Alkoxyamines: a new family of pro-drugs against cancer. Concept for theranostics
Authors: Audran Gérard , Brémond Paul , Franconi Jean-Michel , Marque Sylvain R. A. , Massot Philippe , Mellet Philippe , Parzy Elodie , Thiaudière Eric
Published: December 2013

Concept to apply alkoxyamines as a theranostic against cancer. The success relies on the highly biological generation of an unselective alkyl radical at the right time and at the right place.
Leaderless and leader‐following consensus for heterogeneous multi‐agent systems with random link failures
Authors: Kim Jae Man , Park Jin Bae , Choi Yoon Ho
Published: December 2013

This study investigates the heterogeneous consensus problem for multi‐agent systems with random link failures between each agent. The discrete‐time heterogeneous multi‐agent systems are described by first‐order and second‐order dynamics, and the communication network is assumed to be directed with fixed topology. Since each link between the agents is subject to failure with a certain probability, the control protocol is designed considering the random link failures. The random link failures are presented by a Bernoulli probability sequence, that is, the control protocol for failure occurrence is designed using the one step previous data that is sent by adjacency neighbouring agents. The control protocol for heterogeneous multi‐agent systems is designed for first‐order dynamics and second‐order dynamics using the Lyapunov method. The mean square stability is shown for leaderless and leader‐following heterogeneous multi‐agent systems in terms of a set of linear matrix inequalities, and some simulation results are provided to verify the effectiveness of the proposed methods.
Bidirectional Syntactic Priming across Cognitive Domains: From Arithmetic to Language and Back
Authors: Scheepers Christoph , Sturt Patrick
Published: December 2013

Scheepers et al. [Scheepers, C., Sturt, P., Martin, C. J., Myachykov, A., Teevan, K., & Viskupova, I. (2011). Structural priming across cognitive domains: From simple arithmetic to relative clause attachment. Psychological Science, 22, 1319–1326. doi:10.1177/0956797611416997] showed that the structure of a correctly solved mathematical equation affects how people subsequently complete sentences containing high versus low relative-clause attachment ambiguities. Here we investigated whether such effects generalize to different structures and tasks and, importantly, whether they also hold in the reverse direction (i.e., from linguistic to mathematical processing). In a questionnaire-based experiment, participants had to solve structurally left- or right-branching equations (e.g., 5 × 2 + 7 versus 5 + 2 × 7) and to provide sensicality ratings for structurally left- or right-branching adjective–noun–noun compounds (e.g., alien monster movie versus lengthy monster movie). In the first version of the experiment, the equations were used as primes and the linguistic expressions as targets (investigating structural priming from maths to language). In the second version, the order was reversed (language-to-maths priming). Both versions of the experiment showed clear structural priming effects, conceptually replicating and extending the findings from Scheepers and colleagues (2011). Most crucially, the observed bidirectionality of cross-domain structural priming strongly supports the notion of shared syntactic representations (or recursive procedures to generate and parse them) between arithmetic and language.
International journal editors and East Asian authors: two surveys
Authors: CEREJO Clarinda
Published: December 2013

Countries in East Asia – specifically China, Japan, and South Korea – are rapidly emerging as major contributors to global research output. However, owing to barriers in language and culture, it is possible that authors from these countries face unique challenges in getting published. Moreover, as submissions from these countries increase, journal editors may be able to spot some trends in the problems encountered when processing these submissions. This study presents the results of two surveys – one involving non‐native English‐speaking authors from East Asia and another involving international journal editors. The surveys were designed to throw light on the challenges East Asian authors face in the publication process and the perceptions journal editors have of submissions from East Asian countries. Here, we present and discuss the survey results, highlight gaps in the perspectives of authors and journal editors, and make recommendations to bridge these gaps.
Deficiency of the BiP cochaperone ERdj4 causes constitutive endoplasmic reticulum stress and metabolic defects
Authors: Fritz Jill M. , Dong Mei , Apsley Karen S. , Martin Emily P. , Na Cheng-Lun , Sitaraman Sneha , Weaver Timothy E.
Published: December 2013

Endoplasmic reticulum–localized DnaJ 4 (ERdj4) is an immunoglobulin-binding protein (BiP) cochaperone and component of the endoplasmic reticulum–associated degradation (ERAD) pathway that functions to remove unfolded/misfolded substrates from the ER lumen under conditions of ER stress. To elucidate the function of ERdj4 in vivo, we disrupted the ERdj4 locus using gene trap (GT) mutagenesis, leading to hypomorphic expression of ERdj4 in mice homozygous for the trapped allele (ERdj4GT/GT). Approximately half of ERdj4GT/GTmice died perinatally associated with fetal growth restriction, reduced hepatic glycogen stores, and hypoglycemia. Surviving adult mice exhibited evidence of constitutive ER stress in multiple cells/tissues, including fibroblasts, lung, kidney, salivary gland, and pancreas. Elevated ER stress in pancreatic β cells of ERdj4GT/GTmice was associated with β cell loss, hypoinsulinemia, and glucose intolerance. Collectively these results suggest an important role for ERdj4 in maintaining ER homeostasis during normal fetal growth and postnatal adaptation to metabolic stress.
Do Anterior Cervical Osteophytes Prevent Dynamization of Cervical Dynamic Plates?
Authors: Park Moon Soo , Moon Seong-Hwan , Lee Hwan-Mo , Kim Seok Woo , Kim Tae-Hwan , Min Seul Ki , Suh Bo-Kyung , Riew K. Daniel
Published: December 2013

Study Design:

A retrospective study.

Objective:

To evaluate radiographic changes of patients with osteophytes at the anterior border of the caudal vertebral body who were treated with anterior cervical discectomy and fusion using dynamic rotational plates.

Summary of Background Data:

Dynamic cervical plates are widely used in surgeries of the anterior cervical spine. One concern in using dynamic plates is that the subjacent anterior osteophytes might act as a bony block and prevent dynamization of the plate. To our knowledge, there are no studies that have investigated the validity of this concern.

Materials and Methods:

Twenty-eight patients were selected for the study out of patients who had undergone 1-level anterior cervical discectomy and fusion using a dynamic rotational plate. They were divided into 2 groups on the basis of the presence of osteophytes located at the anterior border of the subjacent vertebrae. Thirteen patients had osteophytes and 15 control patients did not. The mean follow-up period was 10.8±8.4 months (range, 6–36 mo). Lateral radiographs were taken preoperatively, immediately postoperatively, and at the final follow-ups to assess changes in the following radiographic parameters: Cobb angle of the adjacent segments and fused segment, horizontal distance between C2 and C7 plumb lines, height of the bone graft, vertebral heights of the operated segment, and migration distance of the plate.

Results:

No statistical significance was found in the Cobb angles of the adjacent segments and fused segment, distance between the C2–C7 plumb lines, height of the graft, height of vertebral bodies of the operated segment, and migration distance of the plate through the preoperative, postoperative, and final follow-ups between the 2 groups.

Conclusion:

Osteophytes did not appear to affect the dynamization of plates in any of the measured radiographic parameters.