bluuebunny/crossref_metadata_2025 huggingface dataset:
A One‐Pot Oxidation/Enantioselective Oxa‐Michael Cascade
Authors: Willemsen Jorgen S. , Megens Rik P. , Roelfes Gerard , van Hest Jan C. M. , Rutjes Floris P. J. T.
Published: February 2014

A laccase/(2,2,6,6‐tetramethylpiperidin‐1‐yl)oxy (TEMPO) mediated oxidation was combined with an aqueous, enantioselective copper‐catalyzed Michael addition reaction of water in one pot. The copper catalyst was also immobilized onto DNA to induce enantioselectivity in the reaction. Low conversions were observed when the reactions were performed simultaneously, caused by an undesired reaction of an oxidised TEMPO intermediate. We increased the conversions by using a stepwise approach. Thus, after completion of the oxidation, the first reaction was stopped by inhibiting the enzyme with HCO2K and reducing the reactive TEMPO intermediate. Next, the Michael addition reaction was started by adding the Cu catalyst. By applying this strategy, an efficient two‐step one‐pot sequence, proceeding with 20 % ee, was realized. The yield and ee of the second reaction were not affected by the oxidation reaction.
Small sample inference for gamma parameters: one‐sample and two‐sample problems
Authors: Krishnamoorthy K. , León‐Novelo Luis
Published: February 2014

Signed‐likelihood ratio tests (SLRTs) are derived for testing the shape and scale parameters and the mean of a gamma distribution. The properties of the proposed tests are evaluated by Monte Carlo simulation and compared with the other tests available in the literature. SLRTs are also developed for two‐sample problems of comparing two shape parameters, two scale parameters and two means, and their merits are evaluated by Monte Carlo simulation. Evaluation studies indicate that the SLRTs are accurate even for small samples and are comparable with or better than other tests. Furthermore, simple parametric bootstrap (PB) methods based on the maximum likelihood estimates are proposed for interval estimation. The PB confidence intervals are satisfactory even for small samples. The methods are illustrated and compared using two examples. Copyright © 2014 John Wiley & Sons, Ltd.
A stabilized and versatile spatial prediction method for geostatistical models
Authors: Chen Chun‐Shu , Yang Hong‐Ding , Li Yang
Published: February 2014

Geostatistical models are often used to predict spatial variables of interest, but the parameters involved in the spatial correlation function usually cannot be well estimated even if the sample size is large enough under a fixed domain. This would result in the spatial predictor being inaccurate and unstable. In this paper, we apply a data perturbation technique to obtain a new spatial predictor, which is not only continuous but also differentiable with respect to the response variables even after plugging‐in the estimated model parameters. Therefore, it is more stable. Moreover, it is known that different spatial predictors obtained from different methods generally have different levels of performance under different circumstances. To mitigate the uncertainties inherent in a selection process, in this paper, we propose an estimation method of weights based on Stein's unbiased risk estimate to combine candidate stabilized spatial predictors, leading to a versatile spatial predictor that is adaptive to the underlying spatial process. Validity for the proposed spatial prediction method is justified both numerically and theoretically. Furthermore, an application of a real data set for the precipitation levels in the Colorado State is also presented. Copyright © 2014 John Wiley & Sons, Ltd.
Integrating climate and local factors for geomorphological distribution models
Authors: Aalto Juha , Luoto Miska
Published: February 2014

Earth surface processes (ESPs) drive landscape development and ecosystem processes in high‐latitude regions by creating spatially heterogeneous abiotic and biotic conditions. Ongoing global change may potentially alter the activity of ESPs through feedback on ground conditions, vegetation and the carbon cycle. Consequently, accurate modeling of ESPs is important for improving understanding of the current and future distributions of these processes. The aims of this study were to: (1) integrate climate and multiple local predictors to develop realistic ensemble models for the four key ESPs occurring at high latitudes (slope processes, cryoturbation, nivation and palsa mires) based on the outputs of 10 modern statistical techniques; (2) test whether models of ESPs are improved by incorporating topography, soil and vegetation predictors to climate‐only models; (3) examine the relative importance of these variables in a multivariate setting. Overall, the models showed high transferability with the mean area under curve of a receiver operating characteristics (AUC) ranging from 0.83 to 0.96 and true skill statistics (TSS) from 0.52 to 0.87 for the most complex models. Even though the analyses highlighted the importance of the climate variables as the most influential predictors, three out of four models benefitted from the inclusion of local predictors. We conclude that disregarding local topography and soil conditions in spatial models of ESPs may cause a significant source of error in geomorphological distribution models. Copyright © 2014 John Wiley & Sons, Ltd.
Stemflow production and intrastorm rainfall intensity variation: an experimental analysis using laboratory rainfall simulation
Authors: Dunkerley David
Published: February 2014

Laboratory rainfall simulation experiments using a small artificial olive tree are used to show that the fraction of rain falling at a constant intensity that becomes stemflow rises from 9% at 2.5 mm/h to 36.1% at 35 mm/h. Natural rainfall events commonly exhibit wide fluctuations of intensity. Simulated rainfall events each having a mean intensity of 10 mm/h, but containing short intensity peaks of 20 to 100 mm/h at varying intra‐event positions, were used to explore the effect of varying intensity profiles. Results demonstrate that changes in rainfall event profile are associated with wide variation in stemflow flux, stemflow volume and stemflow fraction. When applied to an initially dry plant, rainfall events with a late intensity peak yielded an average peak stemflow flux up to 188% larger than events of contrasting profile, such as early peak events. The increase was smaller, up to 141%, when rain was applied to plants that were already partially wet, but was again found in events with a late intensity peak. Moreover, such events yielded a peak stemflow flux up to approximately seven times larger than comparable events of uniform intensity. Likewise, changing event profile with no change in rainfall depth was associated with a maximum stemflow fraction that was 31% larger than theminimum stemflow fraction, and a maximum stemflow volume that was nearly 37% larger than the minimum stemflow volume. These results suggest that rainfall event profile exerts a significant effect on all of the studied stemflow parameters. It is hypothesized that this is a consequence of the way in which intensity profile affects the rate of wetting‐up of trickle pathways on the plant, and variation in the time taken for these pathways to become fully connected. Event profile must therefore be considered along with plant architecture in seeking to understand stemflow. Copyright © 2014 John Wiley & Sons, Ltd.
Do not only connect: a model of infiltration‐excess overland flow based on simulation
Authors: Kirkby Michael J.
Published: February 2014

The paper focusses on connectivity in the context of infiltration‐excess overland flow and its integrated response as slope‐base overland flow hydrographs. Overland flow is simulated on a sloping surface with some minor topographic expression and spatially differing infiltration rates. In each cell of a 128 × 128 grid, water from upslope is combined with incident rainfall to generate local overland flow, which is stochastically routed downslope, partitioning the flow between downslope neighbours.

Simulations show the evolution of connectivity during simple storms. As a first approximation, total storm runoff is similar everywhere, discharge increasing proportionally with drainage area. Moderate differences in plan topography appear to have only a second‐order impact on hydrograph form and runoff amount.

Total storm response is expressed as total runoff, runoff coefficient or total volume infiltrated; each plotted against total storm rainfall, and allowing variations in average gradient, overland flow roughness, infiltration rate and storm duration. A one‐parameter algebraic expression is proposed that fits simulation results for total runoff, has appropriate asymptotic behaviour and responds rationally to the variables tested. Slope length is seen to influence connectivity, expressed as a scale distance that increases with storm magnitude and can be explicitly incorporated into the expression to indicate runoff response to simple events as a function of storm size, storm duration, slope length and gradient.

The model has also been applied to a 10‐year rainfall record, using both hourly and daily time steps, and the implications explored for coarser scale models. Initial trails incorporating erosion continuously update topography and suggest that successive storms produce an initial increase in erosion as rilling develops, while runoff totals are only slightly modified. Other factors not yet considered include the dynamics of soil crusting and vegetation growth. Copyright © 2014 John Wiley & Sons, Ltd.
Achieving high data rates through full duplex relaying in multicell environments
Authors: Sharma Prabhat Kumar , Garg Parul
Published: February 2014

In this paper, we investigate the outage and error performances of a full duplex relaying cooperative system in a multicell environment, considering the possibility of co‐channel interference from the users located in the nearby cells. The decode‐and‐forward cooperative strategy is assumed at the relay. Throughout the analysis, we consider all the channels to be independent but not necessarily identically distributed as generalised Nakagami‐m fading. We find an accurate closed‐form expression of outage probability and average symbol error rate for integer values of fading parameter m. The analysis considers symmetric M‐ary phase shift keying modulation scheme with equal energy constellation. Copyright © 2014 John Wiley & Sons, Ltd.
Performance Analysis of PEM Fuel Cells with Different Electrical Loads
Authors: San Martín J. I. , Zamora I. , Aperribay V. , San Martín J. J. , Eguía P. , Torres E.
Published: February 2014

One of the most outstanding products of fuel cells is electrical power but, currently, there is a reduced number of publications that provide experimental data about the performance of fuel cells when used for supplying Alternating Current (AC) loads. Most of the existing publications provide experimental data only with direct current (DC) loads, or analyze the performance with AC loads using simulation models. For this reason, this paper analyses experimentally the behavior of a proton exchange membrane fuel cell (PEMFC) system when feeding different electrical loads. The system tested is constituted by a PEM fuel cell, a storage battery, electronic converters and electrical loads. In the tests, the fuel cell system supplies power to three different loads: DC, single‐phase AC and three‐phase AC. For these cases, voltage, current, power, power factor and efficiency data are shown, at different load levels. From those parameters, efficiency of the global system is estimated. Finally, as the power quality concept is a topic of increasing importance when supplying electricity, the total harmonic distortion (THD) of the electric signals has also been analyzed.
Petroleum Term Structure Dynamics and the Role of Regimes
Authors: Nomikos Nikos K. , Pouliasis Panos K.
Published: February 2014

This study investigates the dependence structure between correlated petroleum forward curves. After decomposing the term structure into level, slope, and curvature shocks we develop a flexible multi‐regime error‐correction factor model of the dynamics of the joint evolution of commodity pairs' curves. Volatilities and disequilibria across regimes are markedly different whereas the information content of the suggested framework is also tested in forecasting and value‐at‐risk experiments. The findings of this study have important implications for energy trading and risk management being particularly useful for predicting short‐term spreads and the correlation matrix among traded contracts. © 2014 Wiley Periodicals, Inc. Jrl Fut Mark 35:163–185, 2015
Increased frequency of minimal homozygous deletions is associated with poor prognosis in primary malignant melanoma patients
Authors: Boi Sebastiana , Tebaldi Toma , Re Angela , Cantaloni Chiara , Adami Valentina , Barbareschi Mattia , Cristofolini Mario , Pasini Luigi , Quattrone Alessandro
Published: February 2014

Identification of prognostic melanoma‐associated copy number alterations (CNAs) is still an area of active research. Here, we investigated by high‐resolution array comparative genomic hybridization (aCGH) a cohort of 31 paraffin‐preserved primary malignant melanomas (MMs), whose prognosis was not predictable on the basis of conventional histopathological parameters. Although we identified a variety of highly recurrent sites of genomic lesions, the total number of CNAs per patient was not a discriminator of MM outcome. Furthermore, validation of aCGH by quantitative PCR on an extended population of 65 MM samples confirmed the absence of predictive value for the most recurrent CNA loci. Instead, our analysis revealed specific prognostic potential of the frequency of homozygous deletions (representing less than 3% of the total CNAs on average per sample), which was strongly associated with sentinel lymph node (SLN) invasion (P = 0.003), and distant metastasis (P = 0.003). Increased number of homozygous deletions was also indicative of poor patient survival (P = 0.01), both in our samples and in an independent validation of public dataset of primary and metastatic MMs. Moreover, we identified 77 hotspots of minimal common homozygous deletions, enriched in genes involved in cell adhesion processes and cell‐communication functions, which preferentially accumulated in primary MMs showing the most severe outcome. Therefore, specific loss of gene loci in regions of minimal homozygous deletion may represent a pivotal type of genomic alteration accumulating during MM progression with potential prognostic implication. © 2014 Wiley Periodicals, Inc.
Inhibition of cysteine cathepsin B and L activation in astrocytes contributes to neuroprotection against cerebral ischemia via blocking the tBid‐mitochondrial apoptotic signaling pathway
Authors: Xu Min , Yang Lei , Rong Jia‐Guo , Ni Yong , Gu Wei‐Wei , Luo Yu , Ishidoh Kazumi , Katunuma Nobuhiko , Li Zhong‐Sheng , Zhang Hui‐Ling
Published: February 2014

The roles of cathepsins in the ischemic astrocytic injury remain unclear. Here, we test the hypothesis that activation of cathepsin B and L contributes to the ischemic astrocyte injury via the tBid‐mitochondrial apoptotic signaling pathways. In the rat models of pMCAO, CA‐074Me or Clik148, a selective inhibitor of cathepsin B or cathepsin L, reduced the infarct volume, improved the neurological deficits and increased the MAP2 and GFAP levels. In OGD‐induced astrocyte injury, CA‐074Me or Clik148 decreased the LDH leakage and increased the GFAP levels. In the ischemic cortex or OGD‐induced astrocytes injury, Clik148 or CA‐074Me reversed pMCAO or OGD‐induced increase in active cathepsin L or cathepsin B at 3 h or 6 h, increase in tBid, reduction in mitochondrial cytochrome‐c (Cyt‐c) and increase in cytoplastic Cyt‐c and active caspase‐3 at 12–24 h of the late stage of pMCAO or OGD. CA‐074Me or Clik148 also reduced cytosolic and mitochondrial tBid, increased mitochondrial Cyt‐c and decreased cytoplastic Cyt‐c and active caspase‐3 at 6 h of the early stage of Bid activation. CA‐074Me or Clik148 blocked the pMCAO‐induced release of cathepsin B or L from the lysosomes into the cytoplasm and activation of caspase‐3 in ischemic astrocytes at 12 h after ischemia. Concurrent inhibition of cathepsin B and cathepsin L provided better protection on the OGD‐induced astrocytic apoptosis than obtained with separate use of each inhibitor. These results suggest that inhibition of the cysteine cathepsin B and cathepsin L activation in ischemic astrocytes contributes to neuroprotection via blocking the tBid‐mitochondrial apoptotic signaling pathway. GLIA 2014;62:855–880
A comparison of dual gradient‐echo and spin‐echo fMRI of the inferior temporal lobe
Authors: Halai Ajay D , Welbourne Stephen R , Embleton Karl , Parkes Laura M
Published: February 2014

Magnetic susceptibility differences at tissue interfaces lead to signal loss in conventional gradient‐echo (GE) EPI. This poses a problem for fMRI in language and memory paradigms, which activate the most affected regions. Two methods proposed to overcome this are spin‐echo EPI and dual GE EPI, where two EPI read‐outs are serially collected at a short and longer echo time. The spin‐echo method applies a refocusing pulse to recover dephased MR signal due to static field inhomogeneities, but is known to have a relatively low blood oxygenation level dependant (BOLD) sensitivity. In comparison, GE has superior BOLD sensitivity, and by employing an additional shorter echo, in a dual GE sequence, it can reduce signal loss due to spin dephasing. We directly compared dual GE and spin‐echo fMRI during a semantic categorization task, which has been shown to activate the inferior temporal region—a region known to be affected by magnetic susceptibility. A whole brain analysis showed that the dual GE resulted in significantly higher activation within the left inferior temporal fusiform (ITF) cortex, compared to spin‐echo. The inferior frontal gyrus (IFG) was activated for dual GE, but not spin‐echo. Regions of interest analysis was carried out on the anterior and posterior ITF, left and right IFG, and part of the cerebellum. Dual GE outperformed spin‐echo in the anterior and posterior ITF and bilateral IFG regions, whilst being equal in the cerebellum. Hence, dual GE should be the method of choice for fMRI studies of inferior temporal regions. Hum Brain Mapp 35:4118–4128, 2014. © 2014 Wiley Periodicals, Inc.
Ribavirin improves the IFN-γ response of natural killer cells to IFN-based therapy of hepatitis C virus infection
Authors: Werner Jens M. , Serti Elisavet , Chepa-Lotrea Xenia , Stoltzfus Jonathan , Ahlenstiel Golo , Noureddin Mazen , Feld Jordan J. , Liang Jake T. , Rotman Yaron , Rehermann Barbara
Published: February 2014

Ribavirin (RBV) is an important component of interferon (IFN)-based and direct antiviral treatment regimens for hepatitis C virus (HCV) infection. Immunomodulation, in particular improvement of the host IFN response, has been proposed as RBV's mechanism of action. Natural killer (NK) cells are sensitive biomarkers for IFN-α/β receptor signaling, as NK cell cytotoxicity and IFN-γ production are regulated by signal transducer and activator of transcription (STAT)1- and STAT4-phosphorylation, respectively. Specifically, pSTAT1-dependent NK cell cytotoxicity increases and pSTAT4-dependent IFN-γ production decreases in response to endogenous, virus-induced IFN-α and during IFN-α-based therapy. To assess whether RBV has a direct effect on NK cells and/or improves the IFN-γ response of NK cells in the presence of IFN-α, we prospectively studied 22 HCV patients with and 32 patients without 4 weeks of RBV pretreatment, who all received subsequent pegylated (Peg)IFN/ribavirin combination therapy. During RBV pretreatment, both the frequency of CD56dim NK cells with cytotoxic effector functions and the frequency of CD56bright NK cells with the capacity to produce IFN-γ decreased (P = 0.049 and P = 0.001, respectively). In vitro or in vivo exposure of NK cells to RBV improved the pSTAT4 (P < 0.01) but not pSTAT1 response of NK cells to subsequent stimulation with IFN-α. This was associated with an increase in IFN-γ production but not cytotoxicity of NK cells during subsequent IFN-α-based therapy. The frequency of IFN-γ-producing NK cells was greater in fast second-phase virological responders than in slow responders. Conclusion: RBV enhances the pSTAT4 and IFN-γ response of NK cells to IFN-α-stimulation. (Hepatology 2014;60:1160–1169)
Multigene pathway‐based analyses identify nasopharyngeal carcinoma risk associations for cumulative adverse effects of TERT‐CLPTM1L and DNA double‐strand breaks repair
Authors: Yee Ko Josephine Mun , Dai Wei , Wun Wong Elibe Hiu , Kwong Dora , Tong Ng Wai , Lee Anne , Kai Cheong Ngan Roger , Chung Yau Chun , Tung Stewart , Li Lung Maria
Published: February 2014

The genetic etiology of nasopharyngeal carcinoma (NPC) and mechanisms for inherited susceptibility remain unclear. To examine genetic risk factors for NPC, we hypothesized that heritable risk is attributable to cumulative effects of multiple common low‐risk variants. With the premise that individual SNPs only confer subtle effects for cancer risk, a multigenic pathway‐based approach was used to systematically examine associations between NPC genetic susceptibility with SNPs in genes in DNA repair pathways and from previously identified cancer genome‐wide association study analyses. This case–control study covers 161 genes/loci and focuses on pathway‐based analyses in 2,349 Hong Kong individuals, allowing stratification according to NPC familial status for meaningful association analysis. Three SNPs (rs401681, rs6774494 and rs3757318) corresponding to TERT/CLPTM1L (OR 95% CI = 0.77, 0.68–0.88), MDS1‐EVI1 (OR 95% CI=0.79 0.69–0.89) and CCDC170 (OR 95% CI = 0.76, 0.66–0.86) conferred modest protective effects individually for NPC risk by the logistic regression analysis after multiple testing adjustment (pBonferroni < 0.05). Stratification of NPC according to familial status identified rs2380165 in BLM (OR 95% CI = 1.49, 1.20–1.86, pBonferroni < 0.05) association with family history‐positive NPC (FH+ NPC) patients. Multiple SNPs pathway‐based analysis revealed that the combined gene dosage effects for increasing numbers of unfavorable genotypes in TERT‐CLPTM1L and double‐strand break repair (DSBR) conferred elevated risk in FH+ and sporadic NPC patients (ORs per allele, 95% CIs = 1.37, 1.22–1.55, pBonferroni = 5.00 × 10−6; 1.17, 1.09–1.26, pBonferroni = 4.58 × 10−4, respectively, in TERT/NHEJ pathways). Our data suggested cumulative increased NPC risk associations with TERT‐CLPTM1L and DSBR pathways contribute to genetic susceptibility to NPC and have potential translational relevance for patient stratification and therapeutics.
The heart‐rate‐reducing agent, ivabradine, reduces mechanical allodynia in a rodent model of neuropathic pain
Authors: Noh S. , Kumar N. , Bukhanova N. , Chen Y. , Stemkowsi P.L. , Smith P.A.
Published: February 2014

Background

Peripheral nerve injury increases the excitability of primary sensory neurons. This triggers the onset of neuropathic pain and maintains its persistence. Because changes in hyperpolarization‐activated cyclic nucleotide‐gated cation (HCN) channels are implicated in this process, we examined the action of the heart‐rate‐reducing agent, ivabradine, a clinically approved HCN blocker, in the rat chronic constriction injury (CCI) model of neuropathic pain.

Methods

The effects of ivabradine on mechanical allodynia were assessed using von Frey filaments, and the effects on cardiovascular parameters were monitored by telemetry. Ivabradine block of HCN channels in dorsal root ganglion neurons was confirmed by whole‐cell recording.

Results

In rats subject to CCI, ivabradine (6 mg/kg by gavage twice a day) significantly reduced mechanical allodynia. Cumulative effects were seen with twice daily oral administration over a 4‐day period. Allodynia returned 4 days after the final drug dose. Mean arterial pressure was maintained and only a 15% pharmacological reduction in heart rate was observed. There was no cumulative effect of ivabradine on cardiovascular parameters.

Conclusion

Because ivabradine is effective at an oral dose that produces only moderate pharmacological heart rate reduction, and this is known to be well tolerated in a clinical context, these results underline its possible use in neuropathic pain management.
Differential antinociceptive effects of intrathecal administration of C‐terminal esterified endomorphin‐2 analogues in mice
Authors: Wang C.L. , Xiang Q. , Diao Y.X. , Ren Y.K. , Gu N.
Published: February 2014

Background

We have previously synthesized three esterified endomorphin‐2 (EM‐2) analogues 1–3 by substitution of C‐terminus with methyl, ethyl and tert‐butyl ester, respectively. Interestingly, the increase of EM‐2 in bulkness of the esterified group decreased the μ‐opioid receptor affinity but increased the δ‐affinity. Presently, we extended our studies to investigate the antinociceptive potencies of these esterified analogues given intrathecally in the mouse tail‐flick test. Also, the specific opioid receptor antagonists and antibodies against endogenous opioid peptides were used to determine whether there are any differential mechanisms on the antinociception produced by these analogues.

Methods

Antinociception was assessed using the 50 °C hot water tail‐flick test. The drugs and antibodies were administered intrathecally.

Results

The ED50 value of analogue 1 was 1.34 nmol, exhibiting the highest analgesic effect. In contrast, the antinociceptive potency of analogue 2 was about twofold less potent than that of EM‐2. The antinociception induced by analogues 1 and 2 was mediated by the stimulation of μ‐opioid receptor in the spinal cord. However, the analogue 1‐induced antinociception also contained an additional component that was mediated by the release of dynorphin A acting on κ‐opioid receptor, which was similar to its parent EM‐2. Notably, analogue 3 exhibited only slightly lower analgesia relative to EM‐2, which may possibly be due to a direct stimulation of both μ‐ and δ‐opioid receptors.

Conclusions

Our results demonstrated that EM‐2 and its analogues 1–3 produced differential antinociceptive effects when administered intrathecally. We concluded that C‐terminal amide to esterification conversion changed the antinociceptive potencies and properties of EM‐2.
Laser perforated accordion nerve conduit of poly(lactide‐co‐glycolide‐co‐ɛ‐caprolactone)
Authors: Fukuda Yutaka , Wang Wei , Ichinose Shizuko , Katakura Hiroshi , Mukai Tomokazu , Takakuda Kazuo
Published: February 2014

Accordion nerve conduit of poly(lactide‐co‐glycolide‐co‐ε‐caprolactone) with perforations was developed by excimer laser processing. We evaluated its in vivo function for nerve repairing and discussed the influence of pore size and density. It was found that perforations help inner nerve regeneration remarkably, which effect is unrelated to pore size or density, and is not parallel with revascularization increment. Inducing of permeability only to allow substance exchange but not vessel ingrowth could facilitate nerve regeneration too. Perforating micropores with the size of 100 μm and the density of 25/cm provides permeability and vessel ingrowth both, therefore promotes the axon extension the best, larger, and more pores do not advance axon regeneration more. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 674–680, 2014.
The C-Terminal Domain of Chondroadherin: A New Regulator of Osteoclast Motility Counteracting Bone Loss
Authors: Capulli Mattia , Olstad Ole K , Önnerfjord Patrik , Tillgren Viveka , Muraca Maurizio , Gautvik Kaare M , Heinegård Dick , Rucci Nadia , Teti Anna
Published: February 2014

Chondroadherin (CHAD) is a leucine-rich protein promoting cell attachment through binding to integrin α2β1 and syndecans. We observed that CHAD mRNA and protein were lower in bone biopsies of 50-year-old to 65-year-old osteoporotic women and in bone samples of ovariectomized mice versus gender/age–matched controls, suggesting a role in bone metabolism. By the means of an internal cyclic peptide (cyclicCHAD), we observed that its integrin binding sequence impaired preosteoclast migration through a nitric oxide synthase 2–dependent mechanism, decreasing osteoclastogenesis and bone resorption in a concentration-dependent fashion, whereas it had no effect on osteoblasts. Consistently, cyclicCHAD reduced transcription of two nitric oxide downstream genes, migfilin and vasp, involved in cell motility. Furthermore, the nitric oxide donor, S-nitroso-N-acetyl-D,L-penicillamine, stimulated preosteoclast migration and prevented the inhibitory effect of cyclicCHAD. Conversely, the nitric oxide synthase 2 (NOS2) inhibitor, N5-(1-iminoethyl)-l-ornithine, decreased both preosteoclast migration and differentiation, confirming a role of the nitric oxide pathway in the mechanism of action triggered by cyclicCHAD. In vivo, administration of cyclicCHAD was well tolerated and increased bone volume in healthy mice, with no adverse effect. In ovariectomized mice cyclicCHAD improved bone mass by both a preventive and a curative treatment protocol, with an effect in line with that of the bisphosphonate alendronate, that was mimicked by the NOS2 inhibitor [L-N6-(1-Iminoethyl)-lysine.2 dihydrochloride]. In both mouse models, cyclicCHAD reduced osteoclast and bone resorption without affecting osteoblast parameters and bone formation. In conclusion, CHAD is a novel regulator of bone metabolism that, through its integrin binding domain, inhibits preosteoclast motility and bone resorption, with a potential translational impact for the treatment of osteoporosis. © 2014 American Society for Bone and Mineral Research.
Quantitative investigation of bonding characteristics in ternary Zintl anions: Charge and energy analysis of [Sn2E152(ZnPh)]− (E15 = Sb, Bi) and [Sn2Sb5(ZnPh)2]3−
Authors: Raupach Marc , Dehnen Stefanie , Tonner Ralf
Published: February 2014

The analysis of chemical bonding in Zintl anions and complexes thereof is mostly based on frontier molecular orbital (FMO) analysis. While this approach delivers remarkable insights, it falls short of providing quantitative measures for chemical bonding in these compounds. Here, we investigate the organozinc‐ligated Zintl anions [Sn2E152(ZnPh)]− (E15 = Sb, Bi) and [Sn2Sb5(ZnPh)2]3‐ with charge and energy analysis methods. Partial charge analysis confirms that natural population analysis is more reliable than the Hirshfeld method for the diffuse charge density of the Zintl anions. In a subsequent step, the combined method energy decomposition analysis with natural orbitals for chemical valence is used to deliver quantitative results for the chemical bond between the organozinc fragment and the Zintl anionic cage. From this analysis, we conclude that the shared‐electron description represents the chemical bonding in these compounds more appropriate. The bonding is characterized by a σ‐type bond polarized toward the ZnPh fragment and a strong π‐donation (15–20% of orbital interaction) into the p‐orbitals at zinc. Electrostatic contributions, which are not considered in FMO analyses, make up around two‐thirds of the attractive metal–ligand interaction and should not be neglected in the discussion of chemical bonding in these compounds. Usage of ligands with better σ‐ or π‐accepting ability might thus serve to further stabilize the interesting class of compounds with multinary Zintl anions in the future. © 2014 Wiley Periodicals, Inc.
One‐pot Synthesis of 2,5‐Disubstituted‐1,3,4‐oxadiazoles Based on the Reaction of N,N‐Dimethyl Amides with Acid Hydrazides
Authors: Li Qiang , Tao Yi , Xu Dongfang , Zhang Haobing , Duan Liping
Published: February 2014

Convenient and efficient one pot method for the synthesis of 2,5‐disubstituted‐1,3,4‐oxadiazoles based on the reaction of N,N‐dimethyl amides with acid hydrazides has been developed. The methodology is applied to a wide range of difference aryl hydrazide and difference N,N‐dimethyl amides to 2,5‐disubstituted‐1,3,4‐oxadiazoles yield the in good to excellent yields. It will be possible wide useful application in synthesis.
Flag‐Transitive 2‐ Symmetric Designs with Sporadic Socle
Authors: Tian Delu , Zhou Shenglin
Published: February 2014

Let be a nontrivial 2‐ symmetric design admitting a flag‐transitive, point‐primitive automorphism group G of almost simple type with sporadic socle. We prove that there are up to isomorphism six designs, and must be one of the following: a 2‐(144, 66, 30) design with or , a 2‐(176, 50, 14) design with , a 2‐(176, 126, 90) design with or , or a 2‐(14,080, 12,636, 11,340) design with .
Bone Morphogenetic Protein‐2 Antagonizes Bone Morphogenetic Protein‐4 Induced Cardiomyocyte Hypertrophy and Apoptosis
Authors: Lu Jing , Sun Bo , Huo Rong , Wang Yu‐Chun , Yang Di , Xing Yue , Xiao Xiao‐Lin , Xie Xin , Dong De‐Li
Published: February 2014

Our previous work showed that the expression of bone morphogenetic protein‐4 (BMP4) was up‐regulated in pathological cardiac hypertrophy models and BMP4 induced cardiomyocyte hypertrophy and apoptosis. Bone morphogenetic protein‐2 (BMP2) and BMP4 share greater than 80% amino acid homology and there exists an interaction between BMP2 and BMP4, so the aim of the present study was to elucidate the changes of BMP2 in the cardiac hypertrophy models and the effects of BMP2 on BMP4‐induced cardiomyocyte hypertrophy and apoptosis. The in vivo cardiac hypertrophy models were induced by pressure‐overload and swimming exercise in mice. BMP2 mRNA and protein expressions increased in pressure‐overload and swimming‐exercise induced cardiac hypertrophy. BMP2 itself did not elicit cardiomyocyte hypertrophy and apoptosis, but antagonized BMP4‐induced cardiomyocyte hypertrophy and apoptosis. BMP2 stimulated Akt in cardiomyocytes and Akt inhibitor prevented the antagonism of BMP2 on BMP4‐induced cardiomyocyte apoptosis. Furthermore, BMP2 inhibited BMP4‐induced JNK activation in cardiomyocytes. In conclusion, BMP2 antagonizes BMP4‐induced cardiomyocyte hypertrophy and apoptosis. The anti‐apoptotic effects of BMP2 on BMP4‐induced cardiomyocyte apoptosis might be through activating Akt and inhibiting JNK activation. J. Cell. Physiol. 229: 1503–1510, 2014. © 2014 Wiley Periodicals, Inc.
Influence of the organic loading rate on the hydraulic behaviour and the azo‐dye removal in an anaerobic filter
Authors: Cobos‐Becerra Yazmín Lucero , González‐Martínez Simón
Published: February 2014

BACKGROUND

Biofilm processes have proven to more efficiently remove xenobiotics than suspended growth systems. They offer higher solid retention times to prevent washout of adapted microorganisms. The main problem with anaerobic filters is clogging when the biofilm develops rapidly or after long operating periods. In this work, an anaerobic filter was operated for 466 days to evaluate the degradation of Direct Blue 2 (DB2) azo dye and the influence of organic loading rate on the hydraulic behaviour and on azo dye removal. Axial Dispersion and Wolf and Resnick models were used for the analysis of tracer curves.

RESULTS

Tracer tests showed that the anaerobic filter behaves predominantly as a plug flow reactor and as the biofilm grows thicker with increasing organic load, the void volume and the hydraulic retention time decrease. In addition, with increasing organic loading rate, the dispersion coefficient increases. The anaerobic biofilm removed up to 60% of the Direct Blue 2 azo dye.

CONCLUSION

The higher the organic load, the better the azo dye was removed. Both the dye Direct Blue 2 and its degradation products (benzidine and 4‐aminobiphenyl) can be removed by an anaerobic biofilm. The anaerobic biofilm did not only break the azo bonds but also decomposed benzidine to 4‐aminobiphenyl. © 2014 Society of Chemical Industry
Choice, time and food: continuous cyclical changes in food probability between reinforcers
Authors: Miranda‐Dukoski Ludmila , Davison Michael , Elliffe Douglas
Published: February 2014

The current experiment examined the degree to which locally varying food probabilities on two keys across time since food presentations can continue to control choice until the next food delivery. In two sets of conditions, the probability of food delivery being made available on one key relative to the other key varied sinusoidally across a 1‐min period following each food delivery. In Set 1, food‐probability changes were unsignaled and the number of cycles per min was varied across conditions. In Set 2, there were always two complete cycles of the sinusoid in the 1‐min period, and brief key‐color changes were arranged at a selection of fixed times since food delivery to signal portions of the sinusoid. In Set 1, control of choice by local probability of food on each key decreased over time since food delivery. Control by local food probabilities was greater in conditions that arranged fewer cycles per min. The onset of stimulus changes in Set 2 led to a transient reinstatement of local control by food probabilities regardless of the portion of the sinusoidal variation in food probabilities signaled by the stimuli. However, in conditions where the same colored stimuli signaled different portions of the sinusoidal variation in food‐delivery probabilities, stimulus changes attenuated joint control by elapsed time and food‐probability values. These results suggest that, changing relative food probabilities and stimuli can direct preference toward the likely location of the next food delivery across time since a food presentation, although the degree to which control over choice will be maintained across elapsed time depends on how experimenter‐arranged contingencies are mapped onto elapsed time.
Morphological aspects and expression of estrogen and progesterone receptors in the interdigital sinus in cyclic ewes
Authors: Alexandre‐Pires Graça , Martins Catarina , Miguel Galvão António , Correia Miguel , Ramilo David , Quaresma Mário , Ligeiro Dário , Nunes Telmo , Manuel Caldeira Rui , Ferreira‐Dias Graça
Published: February 2014

Many species that belong to Artiodactyls order show an interdigital sinus (IS), as it occurs in sheep, in all four extremities. These are considered to be scent glands responsible for sexual communication having strong attractiveness to mature males at the peak of the breeding season. The aim of this study was to evaluate, in IS in cyclic ewes, the microscopic and ultrastructure (scanning and transmission electron microscopy) anatomy, secretion composition, and mRNA and protein expression of estrogen receptors α and β and progesterone receptors. Glandular sebaceous structures occupy a superficial area of the pouch. The other glands present in the IS show a coiled tubular structure and tall and polyhedral secretory cells with irregular luminal surface resulting from the secretory process. Protein and mRNA gene transcription studies were performed to determine the presence of ER (α and β) and P4r in IS. At the follicular phase, IS cell populations analyzed using flow cytometry expressed higher levels of ERβ compared with ERα (P < 0.05), whereas no difference was observed between them in the luteal phase. The IS amount of secretion was the highest in the follicular phase compared with luteal phase (P < 0.05) or pregnancy (P < 0.001).To the best of our knowledge, for the first time, the presence of ER (α and β) within the IS was demonstrated. As estrogen action is mediated by specific receptors in target cells, the presence of these receptors in IS might be needed to trigger signaling pathways involved in conspecific chemical (sexual) communication attributed to this area. Microsc. Res. Tech. 77:313–325, 2014. © 2014 The Authors Microscopy Research and Technique Published by Wiley Periodicals, Inc.
Inpatient safety outcomes following the 2011 residency work‐hour reform
Authors: Block Lauren , Jarlenski Marian , Wu Albert W. , Feldman Leonard , Conigliaro Joseph , Swann Jenna , Desai Sanjay V.
Published: February 2014

BACKGROUND

The impact of the 2011 residency work‐hour reforms on patient safety is not known.

OBJECTIVE

To evaluate the association between implementation of the 2011 reforms and patient safety outcomes at a large academic medical center.

DESIGN

Observational study using difference‐in‐differences estimation strategy to evaluate whether safety outcomes improved among patients discharged from resident and hospitalist (nonresident) services before (2008–2011) and after (2011–2012) residency work‐hour changes.

PATIENTS

All adult patients discharged from general medicine services from July 2008 through June 2012.

MEASUREMENTS

Outcomes evaluated included length of stay, 30‐day readmission, intensive care unit (ICU) admission, inpatient mortality, and presence of Maryland Hospital Acquired Conditions. Independent variables included time period (pre‐ vs postreform), resident versus hospitalist service, patient age at admission, race, gender, and case mix index.

RESULTS

Patients discharged from the resident services in the postreform period had higher likelihood of an ICU stay (5.7% vs 4.5%, difference 1.4%; 95% confidence interval [CI]: 0.5% to 2.2%), and lower likelihood of 30‐day readmission (17.2% vs 20.1%, difference 2.8%; 95 % CI: 1.3 to 4.3%) than patients discharged from the resident services in the prereform period. Comparing pre‐ and postreform periods on the resident and hospitalist services, there were no significant differences in patient safety outcomes.

CONCLUSIONS

In the first year after implementation of the 2011 work‐hour reforms relative to prior years, we found no change in patient safety outcomes in patients treated by residents compared with patients treated by hospitalists. Further study of the long‐term impact of residency work‐hour reforms is indicated to ensure improvement in patient safety. Journal of Hospital Medicine 2014;9:347–352. © 2014 Society of Hospital Medicine
HBV genotype C strains with spontaneous YMDD mutations may be a risk factor for hepatocellular carcinoma
Authors: Yang Jiahong , Chen Xuebing , Zhang Hao , Chen Gao
Published: February 2014

HBV has a relatively high mutation rate in its genome and most of these mutations are associated with the curative effect of nucleoside analogs. In this study, 1,424 patients with HBV‐related liver diseases not treated with antiviral drugs, including 197 asymptomatic HBV carriers, 769 chronic hepatitis B patients, 145 acute‐on‐chronic liver failure (ACLF) patients, 187 HBV‐related liver cirrhosis patients, and 126 HBV‐related HCC patients, were selected to investigate the distribution and clinical significance of spontaneous YMDD mutations in liver diseases at different stages. Spontaneous YMDD mutations were detected in all stages of liver diseases and the YIDD variant was the dominant mutation type. The mutation rate was higher in genotype C strains than in genotype B strains. Theχ2subdivision method showed that the spontaneous YMDD mutation rate in HCC was higher than that in other liver diseases. The difference in spontaneous YMDD mutation rates in patients with liver diseases infected with genotype C strains at different stages was statistically significant. Spontaneous YMDD mutation rates in patients with liver diseases infected with genotype C strains at different stages were then compared one to one using theχ2subdivision method. The results showed that the spontaneous YMDD mutation rate in HCC was higher than that in other liver diseases. Taken together, these results indicated that spontaneous YMDD mutations are more likely to occur in patients infected with genotype C strains, and genotype C strains with spontaneous YMDD mutations may be a risk factor for HCC.J. Med. Virol. 86:913–917, 2014.© 2014 Wiley Periodicals, Inc.
Evidence for a change in the epidemiology of hepatitis B virus infection after nearly two decades of universal hepatitis B vaccination in South Africa
Authors: Amponsah‐Dacosta Edina , Lebelo Ramokone L. , Rakgole J. Nare , Burnett Rosemary J. , Selabe Selokela G. , Mphahlele M. Jeffrey
Published: February 2014

The hepatitis B vaccine has been part of the South African Expanded Program on Immunization since April 1995 but its long‐term impact remains unknown. This study tested 1,206 sera collected from patients aged 1–25 years from various health facilities across the country for HBV serological markers and HBV DNA. Based on the year the vaccine was introduced, samples were stratified by age into pre‐ and post‐vaccine introduction populations, which were then compared for evidence of immunity and chronic carriage using the Chi‐square test. Where HIV status was known, subset analyses were performed. Immunity to HBV infection increased from 13.0% in the pre‐ to 57.0% in the post‐vaccine introduction population (P < 0.001). This decreased with increasing age within the post‐vaccine introduction population (76.1% for 1–5 years, 50.0% for 6–10 years, and 46.3% for 11–16 years). In addition, HBV chronic carriage was significantly (P = 0.003) reduced in the post‐ (1.4%) compared to the pre‐vaccine introduction population (4.2%). The difference in prevalence of active HBV infection in the serologically exposed pre‐ and post‐vaccine introduction populations was not statistically significant. Subset analyses showed that evidence of immunity was significantly (P < 0.001) higher in the HIV negative compared to the HIV positive subset in both populations. Universal hepatitis B vaccination has been a remarkable success, with a significant increase in immunity to HBV infection. The observation that HBV chronic carriage increases as immunity wanes over time calls into question whether the time has come to consider a pre‐adolescence vaccine booster dose policy. J. Med. Virol. 86:918–924, 2014. © 2014 Wiley Periodicals, Inc.
Distinct differences in clinical manifestation and viral laboratory parameters between children and adults with influenza A(H1N1)pdm09 infection—A retrospective comparative analysis
Authors: Redlberger‐Fritz Monika , Hirk Sonja , Buchinger Dieter , Haberl Renate , Hell Markus , Perkmann‐Nagele Nicole , Kundi Michael , Popow‐Kraupp Therese
Published: February 2014

During the influenza pandemic 2009 children and adults differed in the clinical course of the influenza disease. In following the question arose, if the case definitions used within the national and international organizations are an adequate tool for the clinical diagnosis of influenza in children as well as in adults. Therefore medical charts from 146 children and 229 adults were retrospectively analyzed. In addition, the initial viral loads of all 375 patients and the duration of virus shedding of a subset of 79 patients were also investigated. Children show a wider clinical spectrum including gastro enteric symptoms and also a different spectrum of laboratory parameters like elevated CRP‐levels, leucocytosis, and higher viral loads. Further, children show significantly more often complications, for example, myositis that may be underdiagnosed. In patients receiving antiviral‐therapy complications occurred significantly less often and the presence of symptoms was significantly shorter compared to the untreated group (2.3 days vs. 6.0 days). In summary, the differences in the clinical picture between children and adults should be taken into consideration for the clinical diagnosis of influenza and also for a future discussion on age specific influenza case definitions. J. Med. Virol. 86:1048–1055, 2014. © 2014 Wiley Periodicals, Inc.
Unified current modeling in low‐dimensional MOSFETs
Authors: Lakhlef Ahcene , Benfdila Arezki , Goudjil Mohamed , Mokdad Rabah
Published: February 2014

The present paper deals with the modeling of low‐dimensional transistors in the form of metal–oxide–semiconductor field‐effect transistors aiming a compact model that may be used to enrich the characterization tools in use and eventually help to extract more information on the interface Si‐SiO2 and the oxide itself. The model is expressed as current versus voltage in the full range and meant to comply with the unified current model.

Our model has been compared with the classical model and found to be in a good agreement in the linear and saturation regions. In addition, our model expresses the current in the subthreshold region, which is not described by the classical model.

The experimental data obtained on research devices are found to suite our model in all the three regions. Copyright © 2014 John Wiley & Sons, Ltd.