bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of hypoxic preconditioning on synaptic ultrastructure in mice
Authors: Liu Yi , Sun Zhishan , Sun Shufeng , Duan Yunxia , Shi Jingfei , Qi Zhifeng , Meng Ran , Sun Yongxin , Zeng Xianwei , Chui Dehua , Ji Xunming
Published: August 2014

Hypoxic preconditioning (HPC) elicits resistance to more drastic subsequent insults, which potentially provide neuroprotective therapeutic strategy, but the underlying mechanisms remain to be fully elucidated. Here, we examined the effects of HPC on synaptic ultrastructure in olfactory bulb of mice. Mice underwent up to five cycles of repeated HPC treatments, and hypoxic tolerance was assessed with a standard gasp reflex assay. As expected, HPC induced an increase in tolerance time. To assess synaptic responses, Western blots were used to quantify protein levels of representative markers for glia, neuron, and synapse, and transmission electron microscopy was used to examine synaptic ultrastructure and mitochondrial density. HPC did not significantly alter the protein levels of astroglial marker (GFAP), neuron‐specific markers (GAP43, Tuj‐1, and OMP), synaptic number markers (synaptophysin and SNAP25) or the percentage of excitatory synapses versus inhibitory synapses. However, HPC significantly affected synaptic curvature and the percentage of synapses with presynaptic mitochondria, which showed concomitant change pattern. These findings demonstrate that HPC is associated with changes in synaptic ultrastructure. Synapse 69:7–14, 2015. © 2014 Wiley Periodicals, Inc.
Estimation of loads on a horizontal axis wind turbine operating in yawed flow conditions
Authors: del Campo V. , Ragni D. , Micallef D. , Diez F. J. , Ferreira C. J. Simão
Published: August 2014

Stereoscopic particle image velocimetry (SPIV) has been used to characterize the flow around the blade of a yawed horizontal axis wind turbine model. The goal was to assess the possibility of obtaining the 3D velocity field around the blade, the pressure distribution, and the aerodynamic loads being exerted on the blade under unsteady flow conditions. The SPIV equipment was mounted on a traverse system and provided with phase‐locked velocity planes perpendicular to the blade axis, scanning the blade from the root to the tip, at three different azimuthal positions, so as to have information of the time variation of the flow. The pressure distribution and the aerodynamic loads on each plane were obtained via 3D formulation. Main differences encountered when measuring loads in yawed flow compared with axial flow have been discussed. Finally, the consistency of the results with similar results obtained computationally with a panel model was assessed. The proposed methodology presents one step further in the application of SPIV to measure forces on a horizontal axis wind turbine, assessing the possibility of estimating the blade loads when the turbine is operating under non‐axial flow conditions, with the goal of better simulating real working operating regimes in a wind farm, where the flow is typically not uniform. The proposed methodology could be developed and used to better understand relevant wind energy issues such as dynamic loading and active load control efficiency, in the future. The processed and averaged flow fields from the experimental SPIV data are made available online to the reader. See appendix for description of the files. Copyright © 2014 John Wiley & Sons, Ltd.
Interaction of thin inclusion with circular hole in the elastic isotropic medium
Authors: Sulym H. , Andrusiv L. , Pasternak Y.
Published: August 2014

The purpose of this paper is to analyze the interaction of thin elastic inclusions with globular defects in a solid structural element and develop technique to determine fracture parameters when the elastic inclusion of the structure is close to a circular hole and/or to its bonding layers. Procedures for determination of fracture parameters are based on the J‐integral relation with generalized stress intensity factors (GSIF) recently obtained by the authors and the boundary element method is adopted for studying thin shapes. The developed techniques, dominating GSIF and mutual integral method, are applied to two specific problems: the interaction of a traction‐free hole with a nearby, thin inclusion and the interaction of a constrained hole with the inclusion. The direct numerical solution was obtained for the two principal models which represent two different boundary conditions on the edge of the hole of the structural element. The study shows that if the hole is unstressed, the values of GSIF are approximately the same as the corresponding values of the fracture parameters and the presence of the hole and the rigid inclusion have only a small effect on GSIF. But if the hole is constrained along its boundary, the values of GSIF generally decrease with decreasing the distance between the inclusion and the hole. The stress concentration on the hole substantially depends on the presence of the inclusion and varies significantly with respect to its radius, the distance from the inclusion, and the relative rigidity of the inclusion.
Bounded elastic potentials for rubberlike materials with strain‐stiffening effects
Authors: Jin Tianfu , Yu Lidan , Yin Zhengnan , Xiao Heng
Published: August 2014

Well‐known models for rubberlike elasticity with strain‐stiffening effects provide good predictions for unlimitedly, rapidly growing stress in a process of approaching a very large strain limit. According to such models, however, unbounded elastic strain energy would be generated as the strain limit is approached. To resolve this issue, a new, explicit approach is proposed to obtain multi‐axial elastic potentials based on uniaxial data and shear data. Then, a strain‐stiffening elastic potential is given to always yield bounded strain energy. Good agreement is achieved with a number of test data.
An open-label study to determine the maximum tolerated dose of the multitargeted tyrosine kinase inhibitor CEP-11981 in patients with advanced cancer
Authors: Pili Roberto , Carducci Michael , Brown Peter , Hurwitz Herbert
Published: August 2014

Background This phase I study evaluated the pharmacokinetics and pharmacodynamics of CEP-11981, an oral vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor, in patients with advanced, relapsed, or refractory solid tumors. Methods Oral CEP-11981 dose escalations followed a modified Fibonacci sequence (from 3.0 to 4.2, 5.9, 11.8, 19.7, 29.6, 41.4, 55.0, 73.0, 97.4, and 126.6 mg/m2). The maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), tumor response, and safety were evaluated. Results CEP-11981 was tolerated at doses between 3.0 and 97.4 mg/m2. The MTD of CEP-11981 was determined to be 97.4 mg/m2, with DLTs observed at the 126.6 mg/m2 dose. The DLTs were grade 4 neutropenia in 1 patient and grade 3 T-wave inversion with chest heaviness and fatigue in 1 patient. All 3 events resolved on stopping CEP-11981. The most frequently reported adverse events of any grade were fatigue, nausea, diarrhea, decreased appetite, abdominal pain, back pain, vomiting, constipation, headache, dizziness, and dyspnea. Treatment-related grade 3/4 neutropenia was observed in the highest-dose cohorts (2 patients at 97.4 mg/m2 and 1 patient at 126.6 mg/m2), indicating some off-target inhibition. VEGF inhibition was greatest in the higher-dose groups. Although no patient experienced complete or partial response, 44 % patients achieved stable disease when measured at ≥ 6 weeks, which occurred more frequently in cohorts receiving ≥ 73.0 mg/m2. Conclusions In patients with recurrent or refractory solid tumors, disease stabilization was achieved. Despite acceptable tolerability of CEP-11981 at the MTD, further development by the sponsor has ceased.
Bully victimization and emotional problems in adolescents: Moderation by specific cognitive coping strategies?
Authors: Garnefski Nadia , Kraaij Vivian
Published: August 2014

Objective

Relationships between bully victimization and symptoms of depression/anxiety were examined. In addition, it was studied whether this relationship was moderated by specific cognitive coping strategies.

Methods

Participants were 582 secondary school students who filled out online self‐report questionnaires on bully victimization, cognitive coping, and depression/anxiety. (Moderated) Multiple Regression analysis was performed.

Results

Strong relationships were found between bully victimization and symptoms of depression and anxiety. On top of that, two cognitive coping strategies moderated the relationship between bullying and depression, i.e. rumination (strengthening) and positive refocusing (reducing). Cognitive coping strategies that moderated the effect of bullying on anxiety symptoms were rumination, catastrophizing (strengthening) and positive reappraisal (reducing).

Conclusion

The results provide possible targets for intervention: when helping adolescents who have been bullied, maladaptive cognitive coping strategies could be assessed and challenged, while more adaptive strategies could be acquired.
H2Me-do2pa: an attractive chelator with fast, stable and inert natBi3+ and 213Bi3+ complexation for potential α-radioimmunotherapy applications
Authors: Lima Luís M. P. , Beyler Maryline , Oukhatar Fatima , Le Saec Patricia , Faivre-Chauvet Alain , Platas-Iglesias Carlos , Delgado Rita , Tripier Raphaël
Published: August 2014

H2Me-do2pa was found to be an efficient ligand for the complexation of Bi3+ and proved to be very attractive for its use for RIT applications.
Creating semantic waves: using Legitimation Code Theory as a tool to aid the teaching of chemistry
Authors: Blackie Margaret A. L.
Published: August 2014

This is a conceptual paper aimed at chemistry educators. The purpose of this paper is to illustrate the use of the semantic code of Legitimation Code Theory in chemistry teaching. Chemistry is an abstract subject which many students struggle to grasp. Legitimation Code Theory provides a way of separating out abstraction from complexity both of which provide substantial challenges to students. These are termed semantic gravity (degree of abstraction) and semantic density (degree of complexity). These ideas are then illustrated using chemical examples in order to demonstrate how they may aid the teaching of chemistry. There is a second pedagogical device which Maton, the developer of Legitimation Code Theory, calls ‘semantic waves’. This is also discussed in the context of chemistry education. The semantic code could be applied to chemistry at all levels.
Late-stage [18F]fluorination: new solutions to old problems
Authors: Brooks Allen F. , Topczewski Joseph J. , Ichiishi Naoko , Sanford Melanie S. , Scott Peter J. H.
Published: August 2014

In this perspective we highlight recent developments and key milestones in “late-stage fluorination” since 2011.
Identification of putative downstream genes of Oct‐3, a pluripotent cell‐specific transcription factor
Authors: Saijoh Yukio , Fujii Hideta , Meno Chikara , Sato Mayumi , Hirota Yoshihiro , Nagamatsu Shinya , lkeda Masako , Hamada Hiroshi
Published: August 2014

Background:  Oct‐3, a pluripotent cell‐specific POU transcription factor, appears to be a key regulator in pluripotential early embryonic cells and germ cells. In order to study how pluripotency is maintained, it is essential to know what genes are regulated by Oct‐3

Results:  By employing a subtraction method, we identified several pluripotent cell‐specific genes. Based upon expression patterns in various cell lines lacking or possessing Oct‐3 function, about half of the genes were placed downstream of Oct‐3. These downstream genes included a previously‐known gene (Glut‐3: a gene for a glucose transporter) and novel genes (226, 383 and 880). Their expression patterns paralleled that of Oct‐3: all of these genes were highly expressed in pluripotent cells such as EC/ES cells, but switched off upon differentiation. More importantly, their expression was rescued in 'revertant' cells that ectopically acquired the Oct‐3 transactivating function. Furthermore, the expression profiles of Glut‐3, 226 and 383 during mouse development also overlapped that of Oct‐3. The Glut‐3 gene possessed multiple Oct‐3 binding sites in its transcriptional regulatory regions, suggesting that at least one of the downstream genes was a direct target of Oct‐3.

Conclusion:  A large proportion of pluripotent cell‐specific genes appear to be downstream targets of Oct‐3.
Recalcitrant pharmaceuticals in the aquatic environment: a comparative screening study of their occurrence, formation of phototransformation products and their in vitro toxicity
Authors: Bergheim Marlies , Gminski Richard , Spangenberg Bernd , Dębiak Malgorzata , Bürkle Alexander , Mersch-Sundermann Volker , Kümmerer Klaus , Gieré Reto
Published: August 2014

Environmental context Many pharmaceuticals on the market have not undergone detailed evaluation for potential aquatic toxicity. We found that most tested pharmaceuticals were persistent, that phototransformation products were likely to be formed as a result of UV treatment of wastewater and that some transformation products were more toxic to bacteria than their precursor pharmaceutical compound. Thus UV treatment of wastewater does not seem appropriate to completely degrade or transform micropollutants into harmless compounds. Abstract Data allowing for a complete environmental risk assessment of pharmaceuticals and their photoderatives in the environment are still scarce. In the present study, in vitro toxicity and both bio- and photopersistence of various pharmaceuticals (aciclovir, allopurinol, cetirizine, cimetidine, fluconazole, hydrochlorothiazide, lisinopril, phenytoin, primidone, ranitidine, sotalol, sulpiride, tramadol and valsartane) as well as their phototransformation products were evaluated in order to fill data gaps and to help prioritise them for further testing. Twelve out of the fourteen compounds investigated were found to be neither readily nor inherently biodegradable in the Organisation of Economic Cooperation and Development-biodegradability tests. The study further demonstrates that the photo-induced transformation of the pharmaceuticals was faster upon irradiation with a Hg lamp (UV light) than with a Xe lamp emitting a spectrum that mimics sunlight. Comparing the non-irradiated with the respective irradiated solutions, a higher acute and chronic toxicity against bacteria was found for the irradiated solutions of seven compounds (cetirizine, cimetidine, hydrochlorothiazide, ranitidine, sulpiride, tramadol and valsartane). No cyto- and genotoxic effects were found in human cervical (HeLa) and liver (Hep-G2) cells for any of the investigated compounds or their phototransformation products. This comparative study documents that phototransformation products can arise as a result of UV treatment of wastewater containing these pharmaceuticals. It further demonstrates that some phototransformation products may have a higher environmental risk potential than the respective parent compounds because some phototransformation products exhibited a higher bacterial toxicity.
Interleukin 11: similar or opposite roles in female reproduction and reproductive cancer?
Authors: Winship Amy , Menkhorst Ellen , Van Sinderen Michelle , Dimitriadis Evdokia
Published: August 2014

During placental development and carcinogenesis, cell invasion and migration are critical events in establishing a self-supporting vascular supply. Interleukin (IL)-11 is a pleiotropic cytokine that affects the invasive and migratory capabilities of trophoblast cells that form the placenta during pregnancy, as well as various malignant cell types. The endometrium is the site of embryo implantation during pregnancy; conversely, endometrial carcinoma is the most common gynaecological malignancy. Here, we review what is known about the role of IL-11 in trophoblast function and in gynaecological malignancies, focusing primarily on the context of the uterine environment.
Changes in the abundance and distribution of the New Zealand fur seal (Arctocephalus forsteri) in Western Australia: are they approaching carrying capacity?
Authors: Campbell Richard , Holley David , Collins Peter , Armstrong Shannon
Published: August 2014

New Zealand fur seals have been increasing in abundance across Australia over the past 20 years, with annual population growth rates of 10–15%. Recent changes in distribution in Western Australia suggested that the population was increasing and expanding in range beyond the known historical distribution. We aimed to determine the growth rate of individual colonies and the overall population across Western Australia and identify new breeding and haulout sites. We used the direct count technique to estimate New Zealand fur seal pup production at 17 breeding sites. We estimated pup production to be 3518 in the 2010/11 austral summer, producing a resultant population estimate of ~17 200 New Zealand fur seals in Western Australia. This represented an exponential growth rate over the past 12 years of ~1% per annum, a significant reduction from the estimated rate of 10% per annum between 1989 and 1999. There were clusters of colonies that showed large annual declines of 6–7% in pup production over the past 12 years and at other colonies maximal rates of increase of pup production were 6–9% per annum. Three new breeding colonies were discovered. It appears that the New Zealand fur seal population is nearing its carrying capacity in Western Australia.
Political dissidents as translators, editors, and publishers
Authors: Ben-Ari Nitsa
Published: August 2014

Against the backdrop of the British mandatory rule of Palestine (1917–1948), Socialist and Revisionist factions struggled bitterly over the character of the new Israeli culture/nation in the making. Crucial ideological differences intermingled with violent fights over topical problems such as whether resistance to British rule should be violent or subdued and how to face growing Arab aggression. The struggle intensified during World War II when the Socialist Zionist camp, headed by Ben-Gurion, backed the British in the war against Nazi Germany. This camp eventually won, as we know, and dissidents found themselves not only jobless but unable to obtain employment in public office. As a result, many Revisionists turned to the private book industry, becoming translators, editors, and publishers. This essay will describe the conditions that led to this choice and will analyze the options left for Revisionist intellectuals rejected by the mainstream. It will then describe them as a far from homogenized sociopolitical group, analyze their various habituses, then present particular examples of participants in the alternative book industry. It will try to find a correlation between their sociopolitical ideology and their professional behavior. Cases of ex-dissidents that found a way into the mainstream will also be presented. Using a diachronic approach, this article will attempt to sum up their contribution, as well as the effects of the strife (schism, in fact) on Hebrew culture that this work represents. Finally, this article will attempt to incorporate these findings within the framework of the sociological turn, problematizing the application of Bourdieu’s habitus and field theories to the study of translation.
The Art of War in retranslating Sun Tzu
Authors: Song Zhongwei
Published: August 2014

The field of translation is a battleground on which, according to Bourdieu, cultural reproducers compete over cultural capital synonymous with higher social status and greater power to control texts and attribute meaning to them. On the surface, the struggles are about defending ideas and satisfying tastes, but they are also about how to control cultural capital and how to eventually convert it into economic capital. Against this background, this article explores the issue of retranslation of classic texts, using Bourdieu’s sociological concepts to analyze why The Art of War is frequently chosen for retranslation, how a challenging translator qualifies himself as someone more capable than his predecessors of doing full justice to the classic text, and, more importantly, what strategies are used to compete against the most respected translators in so doing. The article concludes that retranslating classic texts is a social practice whereby individual translators are inclined to use as their common strategy all kinds of cultural capital (embodied, objectified, and institutionalized) to outmatch the competition not merely within textual practice but also well beyond it.
Is there really a syntactic category of subordination?
Authors: Cristofaro Sonia
Published: August 2014

While different criteria are used in the literature in order to define subordinate clauses, these clauses are generally assumed to form a syntactic category, in the sense of a syntactically defined class that is relevant to speakers of individual languages. Many phenomena that are usually regarded as distinctive for subordination, however, do not actually provide evidence for such a category. This is illustrated in the paper with regard to syntactic embedding. Different criteria provide conflicting evidence as to the embedded vs. nonembedded status of particular clauses, the same criteria give different results for the same clause types in different contexts, and individual criteria do not always make it possible to identify distinct clause classes. This is because the various phenomena that are usually regarded as evidence for embedding are not actually motivated in terms of the same principles, nor are they syntactically motivated. Rather, these phenomena reflect a variety of semantic and pragmatic principles, and in some cases originate from diachronic processes independent of the syntactic status of the relevant clauses.
Rhetorical use of some Finnish conjunctions in constructions and the scope of subordination
Authors: Jääskeläinen Anni
Published: August 2014

This article describes the nature and meaning of a group of constructions that include different conjunctions and onomatopoetic expressions as their elements. Some of these conjunctions are subordinating, while others are coordinating; the constructions thus create depictions of various states of affairs using differing designs of construal, some with a more symmetrical design, others with an asymmetrical design. The tone of each construction varies, depending on the conjunction chosen and the order of the elements. Two types of constructions with subordinating conjunctions kun (‘when’) and kunnes (‘until’) are studied more closely in order to demonstrate how these constructions work and how they acquire their meaning. It will be argued that these constructions are recurring rhetoric patterns of narration and storytelling and that they are best studied as holistic patterns per se, not as sentences that can be divided into separate subordinate or coordinated clauses. It will also be suggested that their narrative power is, however, motivated by the more standard uses of the differing coordinate and subordinate conjunctions. One of these conjunctions is special: kunnes as a conjunction is a narrative device anticipating a dramatic change in the course of action, rather than a means of marking a clause as background information the way subordinating conjunctions normally do. Therefore, if something can be seen as the governing part in this kind of kunnes use, it is not just a single clause but an overall action and chain of events described earlier. Examining these rhetoric structures can shed light on subordination as a phenomenon in general. The article ends with a discussion of subordination, subordinate conjunctions and different descriptions of subordination.
More subordinate?
Authors: Vilkuna Maria
Published: August 2014

Finnish main and subordinate clauses are generally speaking similar in terms of constituent order: both typically obey the default (S)VO (more generally, VX) order. However, the order is flexible so that other, marked orders can be used to express discourse-related meaning, such as topic/focus relations. In addition, verb-final (XV) order typically accompanies clause-initial focusing in utterances that can be called reactive. Although the ordering options may be the same, main and subordinate clauses do not make equal use of them. The present article investigates this issue from the perspective of XV order, which is an option in subordinate clauses particularly in Western Finnish; it is also made use of in Standard Finnish texts, but more marginally. The starting point comes from an article by the Finnish linguist Eeva Lindén (Linden 1959). Lindén’s analysis offers a generalization on the role of subordinate XV order and relates it to clausal order in general, suggesting that XV order it signals subordination. The present article addresses this question by consulting dialectal material just as Lindén did, but by relying on larger corpora and more context. It will be demonstrated that XV ordered clauses are generally backgrounded, their profile overridden by that of another clause, while the default VX ordered clauses are more open and varied in their interpretation, extending to uses that can hardly be claimed to be subordinate by any account. The backgrounded character of XV subordinate clauses consists of factors that ultimately involve reliance on old information. These factors include providing a setting, identifying referents and states of affairs, and being in the scope of the main clause.
Subordination and the prosodic marking of punctuation in L’étranger by Albert Camus
Authors: Wiklund Mari
Published: August 2014

This article examines the role of French prosody in indicating a subordinate relationship between the clauses in L’étranger (The Stranger) by Albert Camus (1942) [1998]. More precisely, this article presents different prosodic realizations of the commas that occur between subordinate clauses and main clauses. The objective of the study is to determine if this particular syntactic position constrains the possible prosodic uses of the comma in French. This analysis has been conducted using the methods adopted in instrumental phonetics. Theoretically, this analysis is based on the predictive intonation theory proposed by Mertens (1987, 2008, 2011).
Colloquialization and “decolloquialization”
Authors: Rodríguez-Puente Paula
Published: August 2014

Given that phrasal verbs are generally related to colloquial styles in Present-day English, the increase of these structures in a particular text type can be interpreted as a sign of colloquialization. Conversely, a decrease in their use may imply the development of more formal, literate features or a tendency towards “decolloqualization”. The present paper examines the development of phrasal verbs in the most formal genres of ARCHER (A Representative Corpus of English Historical Registers), namely medicine, science and sermons. Findings show that the number of phrasal verbs decreases in medicine and science over time, thus displaying a clear tendency towards more literate styles or “decolloquialization”; in sermons, however, phrasal verbs tend to increase. In the light of this evidence, this paper analyzes the differences in use within formal genres, and also compares the use of phrasal verbs between formal and informal genres over time.
New-dialect formation in medieval Ireland
Authors: van Hattum Marije
Published: August 2014

This paper discusses the development of medieval Irish English (MIrE) within the model of new-dialect formation (NDF) (Trudgill 2004). In particular, the processes of interdialect development, reallocation, and focusing are discussed with respect to data from sixteen MIrE poems from Harley 913 (c.1330). The data show traces of NDF, especially with respect to dialect mixing and novel forms, but they also show a lack of focusing in comparison to the model of NDF and to contemporary Middle English poems. I suggest that this lack of focusing is due to the lack of a standardized variety of English in general. In addition, factors such as the amount of contact between the settlers and the identity of the old(er) versus the new(er) settlers might have played a role as well. Thus my paper hopes to contribute to the discussion on new-dialect formation in general and the development of MIrE in particular.
Differences in the regulation of RyR2 from human, sheep, and rat by Ca2+ and Mg2+ in the cytoplasm and in the lumen of the sarcoplasmic reticulum
Authors: Walweel Kafa , Li Jiao , Molenaar Peter , Imtiaz Mohammad S. , Quail Anthony , dos Remedios Cris G. , Beard Nicole A. , Dulhunty Angela F. , van Helden Dirk F. , Laver Derek R.
Published: August 2014

Regulation of the cardiac ryanodine receptor (RyR2) by intracellular Ca2+ and Mg2+ plays a key role in determining cardiac contraction and rhythmicity, but their role in regulating the human RyR2 remains poorly defined. The Ca2+- and Mg2+-dependent regulation of human RyR2 was recorded in artificial lipid bilayers in the presence of 2 mM ATP and compared with that in two commonly used animal models for RyR2 function (rat and sheep). Human RyR2 displayed cytoplasmic Ca2+ activation (Ka = 4 µM) and inhibition by cytoplasmic Mg2+ (Ki = 10 µM at 100 nM Ca2+) that was similar to RyR2 from rat and sheep obtained under the same experimental conditions. However, in the presence of 0.1 mM Ca2+, RyR2s from human were 3.5-fold less sensitive to cytoplasmic Mg2+ inhibition than those from sheep and rat. The Ka values for luminal Ca2+ activation were similar in the three species (35 µM for human, 12 µM for sheep, and 10 µM for rat). From the relationship between open probability and luminal [Ca2+], the peak open probability for the human RyR2 was approximately the same as that for sheep, and both were ∼10-fold greater than that for rat RyR2. Human RyR2 also showed the same sensitivity to luminal Mg2+ as that from sheep, whereas rat RyR2 was 10-fold more sensitive. In all species, modulation of RyR2 gating by luminal Ca2+ and Mg2+ only occurred when cytoplasmic [Ca2+] was <3 µM. The activation response of RyR2 to luminal and cytoplasmic Ca2+ was strongly dependent on the Mg2+ concentration. Addition of physiological levels (1 mM) of Mg2+ raised the Ka for cytoplasmic Ca2+ to 30 µM (human and sheep) or 90 µM (rat) and raised the Ka for luminal Ca2+ to ∼1 mM in all species. This is the first report of the regulation by Ca2+ and Mg2+ of native RyR2 receptor activity from healthy human hearts.
K+ channel gating: C-type inactivation is enhanced by calcium or lanthanum outside
Authors: Armstrong Clay M. , Hoshi Toshinori
Published: August 2014

Many voltage-gated K+ channels exhibit C-type inactivation. This typically slow process has been hypothesized to result from dilation of the outer-most ring of the carbonyls in the selectivity filter, destroying this ring’s ability to bind K+ with high affinity. We report here strong enhancement of C-type inactivation upon extracellular addition of 10–40 mM Ca2+ or 5–50 µM La3+. These multivalent cations mildly increase the rate of C-type inactivation during depolarization and markedly promote inactivation and/or suppress recovery when membrane voltage (Vm) is at resting levels (−80 to −100 mV). At −80 mV with 40 mM Ca2+ and 0 mM K+ externally, ShBΔN channels with the mutation T449A inactivate almost completely within 2 min or less with no pulsing. This behavior is observed only in those mutants that show C-type inactivation on depolarization and is distinct from the effects of Ca2+ and La3+ on activation (opening and closing of the Vm-controlled gate), i.e., slower activation of K+ channels and a positive shift of the mid-voltage of activation. The Ca2+/La3+ effects on C-type inactivation are antagonized by extracellular K+ in the low millimolar range. This, together with the known ability of Ca2+ and La3+ to block inward current through K+ channels at negative voltage, strongly suggests that Ca2+/La3+ acts at the outer mouth of the selectivity filter. We propose that at −80 mV, Ca2+ or La3+ ions compete effectively with K+ at the channel’s outer mouth and prevent K+ from stabilizing the filter’s outer carbonyl ring.
Folding similarity of the outer pore region in prokaryotic and eukaryotic sodium channels revealed by docking of conotoxins GIIIA, PIIIA, and KIIIA in a NavAb-based model of Nav1.4
Authors: Korkosh Viacheslav S. , Zhorov Boris S. , Tikhonov Denis B.
Published: August 2014

Voltage-gated sodium channels are targets for many drugs and toxins. However, the rational design of medically relevant channel modulators is hampered by the lack of x-ray structures of eukaryotic channels. Here, we used a homology model based on the x-ray structure of the NavAb prokaryotic sodium channel together with published experimental data to analyze interactions of the μ-conotoxins GIIIA, PIIIA, and KIIIA with the Nav1.4 eukaryotic channel. Using Monte Carlo energy minimizations and published experimentally defined pairwise contacts as distance constraints, we developed a model in which specific contacts between GIIIA and Nav1.4 were readily reproduced without deformation of the channel or toxin backbones. Computed energies of specific interactions between individual residues of GIIIA and the channel correlated with experimental estimates. The predicted complexes of PIIIA and KIIIA with Nav1.4 are consistent with a large body of experimental data. In particular, a model of Nav1.4 interactions with KIIIA and tetrodotoxin (TTX) indicated that TTX can pass between Nav1.4 and channel-bound KIIIA to reach its binding site at the selectivity filter. Our models also allowed us to explain experimental data that currently lack structural interpretations. For instance, consistent with the incomplete block observed with KIIIA and some GIIIA and PIIIA mutants, our computations predict an uninterrupted pathway for sodium ions between the extracellular space and the selectivity filter if at least one of the four outer carboxylates is not bound to the toxin. We found a good correlation between computational and experimental data on complete and incomplete channel block by native and mutant toxins. Thus, our study suggests similar folding of the outer pore region in eukaryotic and prokaryotic sodium channels.
Efficacy and tolerability of luliconazole cream 1% for dermatophytoses: A Meta‐analysis
Authors: Feng Xiaowei , Xie Jinwei , Zhuang Kaiwen , Ran Yuping
Published: August 2014

We evaluated the efficacy and safety of luliconazole cream 1% in the treatment of dermatophytoses. According to our meta‐analysis, short‐term treatment of luliconazole cream 1% can result in the complete clearance of dermatophytoses. It showed that 1% luliconazole was more effective than controlled drugs or vehicle (week 4: odds ratio = 1.46, 95% confidence interval = 1.12–1.91), and no more adverse events occurred in the 1% luliconazole group (week 4: odds ratio = 1.01, 95% confidence interval = 0.71–1.44). This effect strengthens the evidence for luliconazole cream 1% being more effective than vehicle, 1% terbinafine, 1% bifonazole, and 0.1% or 0.5% luliconazole.
Anti‐allergic mechanisms of Japanese herbal medicine, yokukansan on mast cells
Authors: Yamamura Kazuhiko , Kato Shiori , Kato Takahiro A. , Mizoguchi Yoshito , Monji Akira , Kanba Shigenobu , Furue Masutaka , Takeuchi Satoshi
Published: August 2014

We previously reported that the addition of orally administered yokukansan (YKS), a traditional Japanese herbal medicine, to the standard regimen using histamine H1‐receptor inhibitors was effective in controlling refractory chronic urticaria, but the mechanism remained unknown. YKS has also been reported to be effective on inhibiting the development of atopic dermatitis‐like skin lesions in NC/Nga mice. As known, the release of various chemical mediators including histamine from degranulated mast cells is strongly related to the mechanism of these diseases. Thus the purpose of this study was to examine the mechanisms behind the medicinal effects of YKS on mast cells using an in vitro system and rat basophil leukemia (RBL‐2H3) cells. The degree of degranulation was measured by β‐hexosaminidase secretion assay and intracellular calcium influx assay. ELISA for cytokines (TNF‐α and IL‐4) was also conducted using cell culture media. Furthermore, we investigated the effects of YKS on the expression of adhesion molecules (ICAM‐1, VCAM‐1, E‐selectin) and cytokine production (IL‐8) in human dermal microvascular endothelial cells using gene‐transcriptional‐ and immunohisotoligical analysis. We found that YKS inhibited secretion of β‐hexosaminidase, intracellular calcium increase, production of TNF‐α and ICAM‐1 expression, and that several YKS ingredients may be the key effectors. In conclusion, YKS may suppress several mast cell functions such as degranulation and calcium increase that eventually inhibits the release of proinflammatory cytokines. Furthermore, YKS suppresses ICAM‐1 expression on human microvascular endothelial cells. These findings may promote our understanding of the beneficial effects of YKS on mast cell‐associated allergic diseases.
Histopathological investigation of clinically non‐affected perilesional scalp in alopecias detected unexpected spread of disease activities
Authors: Watanabe‐Okada Emiko , Amagai Masayuki , Ohyama Manabu
Published: August 2014

Histopathological comparison between clinically affected and intact regions in alopecia patients has been considered to facilitate better understanding of the pathophysiology of ongoing disease. Theoretically, adjacent intact regions should provide ideal controls as they should share close histological characteristics, however, to what extent clinically non‐affected neighboring regions maintain their pathological integrity has not been fully assessed. The goal of this study is to delineate histopathological characteristics of clinically intact perilesional regions in the patients with various forms of alopecia. Transverse sections of 4‐mm punch biopsy at the levels of isthmus and suprabulbar portion were obtained from seemingly unimpaired perilesional scalp of 50 Japanese alopecia patients (16 alopecia areata [AA] multiplex, 19 scarring alopecia [SA], 15 other conditions) and subject to histopathological investigation. Initial screening detected decrease in anagen (anagen : telogen ratio = 82.4:17.6) when compared with previously reported standard hair counts in normal Asian scalp. This finding prompted further investigation. Unexpectedly, 33 (66%) specimens demonstrated some microscopic abnormalities, 10 (62.5%) AA specimens showed increase in telogen ratio, vellus hair count and miniaturization, while perifollicular inflammatory cell infiltration was detected in 5 (26.3%) SA cases. Exclusion of histologically affected specimens yielded average hair count numbers resembling those reported in Koreans, supporting the pathological integrity of selected samples and, more importantly, indicating normal hair counts in east Asians. These findings indicated a less recognized significance of histopathological investigation of clinically non‐affected perilesional scalp in alopecias for better assessment of the spread of disease activities, which should enable better management of hair loss conditions.
Heat stress is a potent stimulus for enhancing rescue efficiency of recombinant Borna disease virus
Authors: Kojima Shohei , Honda Tomoyuki , Matsumoto Yusuke , Tomonaga Keizo
Published: August 2014

Recently developed vector systems based on Borna disease virus (BDV) hold promise as platforms for efficient and stable gene delivery to the central nervous system (CNS). However, because it currently takes several weeks to rescue recombinant BDV (rBDV), an improved rescue procedure would enhance the utility of this system. Heat stress reportedly enhances the rescue efficiency of other recombinant viruses. Here, heat stress was demonstrated to increase the amount of BDV genome in persistently BDV‐infected cells without obvious cytotoxicity. Further analyses suggested that the effect of heat stress on BDV infection is not caused by an increase in the activity of BDV polymerase. More cells in which BDV replication occurs were obtained in the initial phase of rBDV rescue by using heat stress than when it was not used. Thus, heat stress is a useful improvement on the published rescue procedure for rBDV. The present findings may accelerate the practical use of BDV vector systems in basic science and the clinic and thus enable broader adoption of this viral vector, which is uniquely suited for gene delivery to the CNS.
Comparison Between 2 Methods of Solid–Liquid Extraction for the Production of Cinchona calisaya Elixir: An Experimental Kinetics and Numerical Modeling Approach
Authors: Naviglio Daniele , Formato Andrea , Gallo Monica
Published: August 2014

The purpose of this study is to compare the extraction process for the production of China elixir starting from the same vegetable mixture, as performed by conventional maceration or a cyclically pressurized extraction process (rapid solid–liquid dynamic extraction) using the Naviglio Extractor. Dry residue was used as a marker for the kinetics of the extraction process because it was proportional to the amount of active principles extracted and, therefore, to their total concentration in the solution. UV spectra of the hydroalcoholic extracts allowed for the identification of the predominant chemical species in the extracts, while the organoleptic tests carried out on the final product provided an indication of the acceptance of the beverage and highlighted features that were not detectable by instrumental analytical techniques. In addition, a numerical simulation of the process has been performed, obtaining useful information about the timing of the process (time history) as well as its mathematical description.
Post‐flowering photoperiod has marked effects on fruit chemical composition in red raspberry (Rubus idaeus)
Authors: Mazur S.P. , Sønsteby A. , Wold A.‐B. , Foito A. , Freitag S. , Verrall S. , Conner S. , Stewart D. , Heide O.M.
Published: August 2014

The effect of photoperiod on nutritional quality and chemical composition of ‘Glen Ample’ red raspberry has been studied under controlled environment conditions. Long day (LD) conditions during fruit growth and maturation significantly increased fruit concentrations of ascorbic acid, total phenolics, organic acids such as malic, quinic and ellagic acids, as well as the ferric reducing activity power, while reducing the concentrations of soluble solids, sucrose and the sugar/acid ratio. The levels of total anthocyanin and oxalic acid were not significantly affected by photoperiod whereas semi‐quantitative analysis indicated a significant increase in the levels of some ellagitannins. The same responses were found whether LD was established by day‐length extension with low‐intensity light or by night interruption, thus demonstrating that the observed changes in nutritional quality of raspberry fruit was mediated through specific photoperiodic mechanism(s) independently of the daily light energy supply.
Age‐Related Effects of Alcohol from Adolescent, Adult, and Aged Populations Using Human and Animal Models
Authors: Squeglia Lindsay M. , Boissoneault Jeff , Van Skike Candice E. , Nixon Sara Jo , Matthews Douglas B.
Published: August 2014

Background

This review incorporates current research examining alcohol's differential effects on adolescents, adults, and aged populations in both animal and clinical models.

Methods

The studies presented range from cognitive, behavioral, molecular, and neuroimaging techniques, leading to a more comprehensive understanding of how acute and chronic alcohol use affects the brain throughout the life span.

Results

Age of life is a significant factor in determining the effect of alcohol on brain functioning. Adolescents and aged populations may be more negatively affected by heavy alcohol use when compared to adults.

Conclusions

Investigations limiting alcohol effects to a single age group constrains understanding of differential trajectories and outcomes following acute and chronic use. To meaningfully address the sequencing and interaction effects of alcohol and age, the field must incorporate collaborative and integrated research efforts focused on interdisciplinary questions facilitated by engaging basic and applied scientists with expertise in a range of disciplines including alcohol, neurodevelopment, and aging.
Can Excellence in Corporate Social Performance Improve Investors' Financial Assessments and Credibility of Managers' Forecasts?
Authors: Guiral Andres , Moon Doocheol , Choi Hyunjung
Published: August 2014

In contrast to the extensive archival research on the relationship between corporate social performance and financial performance, behavioral studies are scarce. We explore whether excellence in corporate social performance affects investors' judgments of financial assessments (i.e., future profitability, liquidity, and financial risk) and credibility of management's forecasts. We define “excellence in corporate social performance” as the case of a firm simultaneously showing high and stable social performance and being provided with professional assurance on social activity reporting. We design a 2 × 2 experimental design with two control groups by manipulating corporate social performance (high versus low) and assurance (present versus absent), in which investors are asked to provide their judgments on the financial status of the firm. Our results indicate that corporate social performance excellence has an impact on both investors' financial assessments and their reliance on management‐forecasted information. Additional analysis shows that corporate social performance excellence is perceived as having a significantly higher impact on investors' financial assessments and their credibility of managers' forecasts in comparison with temporary corporate social performance. Therefore, we find support for the argument that only the combination of superior and stable corporate social performance and reliable corporate social responsibility disclosure pays off.
Stock Price Reactions to News and the Momentum Effect in the Korean Stock Market
Authors: Lee Dongweon , Cho Jaeho
Published: August 2014

By analyzing how stock prices respond to public news, this paper examines the momentum effect in the Korean stock market. It is true that, as a whole, the momentum strategy generates no profits in Korea. However, among the stocks in a momentum portfolio, loser stocks with news headlines make significantly positive profits caused by negative return drift. These positive profits are cancelled out by negative returns, due mostly to reversals exhibited by winner stocks with and without public news. These reversals stand in contrast to the case of the United States market, where winner stocks show weak drift (Chan, 2003). Reversals of news winners and the drift of news losers in Korea imply that stock prices react asymmetrically to public news, which is overlooked in existing studies on momentum. Further analyses indicate that this asymmetric reaction can be attributed to transaction costs rather than to the incentive of managers to disclose bad news slowly. In addition to the asymmetric reaction of prices to news, we suggest that market misperceptions concerning firms' future prospects may also be a reason for the post‐news return patterns in Korea.
Valuation of Guaranteed Contracts Set Relative to Cross‐currency Stochastic Rates of Return
Authors: Hsieh Tsung‐Yu , Chou Chi‐Hsun , Chen Son‐Nan
Published: August 2014

We derive the pricing formulas for guaranteed contracts with guaranteed minimum rates of return linked to cross‐currency stochastic rates of return under a cross‐currency framework. These rates are often embedded in contracts such as life and pension insurance policies, guaranteed investment contracts, and index‐linked bonds. Valuation of such contracts has not been investigated in the previous literature. Our research finds that the past valuation of these rates via a single‐currency framework causes significant underestimation under both maturity and (especially) multi‐period guarantees. Our pricing formulas are more suitable, tractable, and feasible in practice than those in the previous literature.