bluuebunny/crossref_metadata_2025 huggingface dataset:
Desiring a career in STEM‐related fields: How middle school girls articulate and negotiate identities‐in‐practice in science
Authors: Tan Edna , Calabrese Barton Angela , Kang Hosun , O'Neill Tara
Published: October 2013

The underrepresentation of non‐White students and girls in STEM fields is an ongoing problem that is well documented. In K‐12 science education, girls, and especially non‐White girls, often do not identify with science regardless of test scores. In this study, we examine the narrated and embodied identities‐in‐practice of non‐White, middle school girls who articulate future career goals in STEM‐related fields. For these girls who desire an STEM‐related career, we examine the relationships between their narrated and embodied identities‐in‐practice. Drawing on interview and ethnographic data in both school and after school science contexts, we examine how STEM‐career minded middle school girls articulate and negotiate a path for themselves through their narratives and actions. We present four types of relationships between girls' narrated and embodied identities‐in‐practice, each with a representative case study: (1) partial overlaps, (2) significant overlaps, (3) contrasting, and (4) transformative. The implications of these relationships with regard to both hurdles and support structures that are needed to equip and empower girls in pursuit of their STEM trajectories are discussed. © 2013 Wiley Periodicals, Inc. J Res Sci Teach 50: 1143–1179, 2013
Electrochemotherapy Treatment of Locally Advanced and Metastatic Soft Tissue Sarcomas: Results of a Non‐Comparative Phase II Study
Authors: Campana Luca G. , Bianchi Giuseppe , Mocellin Simone , Valpione Sara , Campanacci Laura , Brunello Antonella , Donati Davide , Sieni Elisabetta , Rossi Carlo R.
Published: October 2013

Aims

Our aim was to evaluate the activity, toxicity, and feasibility of electrochemotherapy (ECT) in patients with soft‐tissue sarcomas (STS).

Methods

A two‐stage phase II trial was conducted between October 2006 and March 2012. Patients (N = 34) with locally advanced or metastatic STS, unsuitable for standard oncological treatments and with maximum 3‐cm deep tumors, received an intravenous bolus of bleomycin (15,000 IU/m2), followed by tumor electroporation according to the European Standard Operating Procedures of ECT. Outcome measures included local response according to response evaluation criteria in solid tumors (RECIST), toxicity and tumor control. Feasibility measures included the accuracy of electrode placement and the intensity of electric current flowing in tumor tissue.

Results

Median tumor size was 4.0 cm (range 2–12). Objective response, assessed on 71 target lesions, was 92.2 % (complete 32.3, 95 % CI 28–64). A total of 15 patients received up to four cycles due to incomplete response, but re‐treatment did not significantly improve outcome (p = 0.205). After a median follow‐up of 19.3 months, 2‐year local control rate was 72.5 %. Median time to local failure (N = 11 patients) was 5.1 months. Tumor response (p = 0.041) and control (p = 0.047) correlated with histological grading. Relevant toxicity consisted of G3 skin ulceration and soft tissue necrosis (35 and 23 % of patients, respectively), although this was manageable on an outpatient basis. The accuracy of electrode placement was 47.1 %, and the adequacy of electroporative current 85.3 %.

Conclusions

ECT may represent an active and safe treatment to achieve local control in advanced STS patients with symptomatic disease. Future research challenges include the improvement of electrode placement and voltage delivery together with the containment of soft tissue toxicity.
Effect of vane thickness on radiometric force
Authors: Ventura Austin , Gimelshein Natalia , Gimelshein Sergey , Ketsdever Andrew
Published: October 2013

A numerical and experimental study of radiometric forces on vanes of different thickness is presented for the flow regime where the radiometric force is near its maximum. For single- and multi-vane geometries, it is shown that radiometric force decreases by only ∼10–15 % when the vane thickness-to-height ratio increases fourfold from 0.5 to 2. For a single-vane geometry, the shear force on the lateral side of the vane is attributed to a vortex flow generated by the interaction of cold chamber walls and heated walls of the vane. In that case, it always acts to reduce the total radiometric force governed by the pressure difference between the hot and the cold sides of the vane. For a multi-vane geometry, represented by a perforated vane, the shear force becomes positive for larger thickness-to-height ratios and lower pressures, primarily due to strong vane-driven transpiration flow through the gaps.
Turbulent pipe flow downstream of a bend
Authors: Hellström Leo H. O. , Zlatinov Metodi B. , Cao Guangjun , Smits Alexander J.
Published: October 2013

Time-resolved stereoscopic PIV was used to investigate the curvature-induced structures downstream of a$90{{}^\circ} $bend at Reynolds numbers between$20\times 1{0}^{3} $and$115\times 1{0}^{3} $. Data were taken at three downstream locations to investigate the evolution of the structures. Snapshot proper orthogonal decomposition (POD) analysis shows that the most energetic structure is not the well-known Dean motion but a bimodal single cell structure with alternating direction of rotation, called the ‘swirl switching’ mode. The strengths of the Dean motion and the swirl-switching structures are similar, indicating that the difference in energy is related to their duration of occurrence, where the Dean motion is associated with a comparatively rapid transition between the two states in the swirl switching mode.
A Recommendation for Expanding the Definition of Moral Distress Experienced in the Workplace
Authors: Crane Monique Frances , Bayl-Smith Piers , Cartmill John
Published: October 2013

Despite the importance of moral distress in the nursing scholarship, little attention is paid to the phenomena in the psychological literature as an important occupational stressor. A factor limiting the application of moral distress to other occupational settings is its definitional features. First, a necessary condition of moral distress is the acknowledgment prior to behaviour initiation that behaviour will contravene personal moral ideals. Second, the definition of moral distress specifies that the inability to act in accordance with one's moral framework is driven by institutional constraints (non-autonomous behaviour). This article proposes that moral distress not be limited in these ways, and makes two central contributions to resolve this core problem. We offer a critique and extension of the conceptual definition of moral distress. Fourteen Australian medical doctors participated in a semi-structured interview regarding occupational morally distressing events. Medical doctors were chosen for our interviews because they are an occupational population with considerable decision-making autonomy. Based on the findings, two recommendations are made: (1) that the definition of moral distress is not limited to events where decision-making and behaviour is non-autonomous, and (2) moral distress should not be limited to occasions where the moral conflict is identified prior to decision-making or behaviour. An alternative definition of moral distress is proposed. We conclude that while organisational limitations are an important precipitate of moral distress, they are not a necessary condition for its emergence.
The formation of secure new attachments by children who were maltreated: An observational study of adolescents in foster care
Authors: Joseph Michelle A. , O'Connor Thomas G. , Briskman Jacqueline A. , Maughan Barbara , Scott Stephen
Published: October 2013

Children who were maltreated and enter foster care are at risk for maladjustment and relationship disturbances with foster carers. A popular hypothesis is that prior attachment relationships with abusive birth parents are internalized and carried forward to impair the child's subsequent attachment relationships. However, the empirical base for this model is limited, especially in adolescence. We examined the attachment patterns of 62 adolescents with their birth parents and their foster parents; we compared them to a comparison sample of 50 adolescents in normal-risk families. Attachment was assessed using the Child Attachment Interview; adolescent–parent interaction quality was assessed from direct observation; disruptive behavior symptoms were assessed from multiple informants. Whereas nearly all of the adolescents in foster families exhibited insecure attachments to their birth mothers (90%) and birth fathers (100%), nearly one-half were classified as having a secure attachment with their foster mother (46%) and father (49%); rates of secure attachment toward foster parents did not differ significantly from the rate in comparison families. Within the foster care sample, attachment security to the foster mother was predicted from current observed relationship quality and the duration of current placement. In addition, attachment quality in foster adolescents was associated with fewer disruptive behavior symptoms, and this association was equally strong in foster and comparison families. Our findings demonstrate that there is substantial potential for maltreated children to change and develop subsequent secure attachments in adolescence.
Interaction with both ZNRF3 and LGR4 is required for the signalling activity of R‐spondin
Authors: Xie Yang , Zamponi Raffaella , Charlat Olga , Ramones Melissa , Swalley Susanne , Jiang Xiaomo , Rivera Daniel , Tschantz William , Lu Bo , Quinn Lisa , Dimitri Chris , Parker Jefferson , Jeffery Doug , Wilcox Sheri K , Watrobka Mike , LeMotte Peter , Granda Brian , Porter Jeffrey A , Myer Vic E , Loew Andreas , Cong Feng
Published: October 2013

R‐spondin proteins sensitize cells to Wnt signalling and act as potent stem cell growth factors. Various membrane proteins have been proposed as potential receptors of R‐spondin, including LGR4/5, membrane E3 ubiquitin ligases ZNRF3/RNF43 and several others proteins. Here, we show that R‐spondin interacts with ZNRF3/RNF43 and LGR4 through distinct motifs. Both LGR4 and ZNRF3 binding motifs are required for R‐spondin‐induced LGR4/ZNRF3 interaction, membrane clearance of ZNRF3 and activation of Wnt signalling. Importantly, Wnt‐inhibitory activity of ZNRF3, but not of a ZNRF3 mutant with reduced affinity to R‐spondin, can be strongly suppressed by R‐spondin, suggesting that R‐spondin primarily functions by binding and inhibiting ZNRF3. Together, our results support a dual receptor model of R‐spondin action, where LGR4/5 serve as the engagement receptor whereas ZNRF3/RNF43 function as the effector receptor.
The adaptor protein Crk in immune response
Authors: Liu Dongfang
Published: October 2013

The adaptor proteins Crk (CT10 (chicken tumor virus number 10) regulator of kinase), including CrkI, CrkII and Crk‐like, are important signal molecules that regulate a variety of cellular processes. Considerable progress has been made in understanding the roles of the Crk family proteins in signal transduction, with a focus on cellular transformation and differentiation. However, since Crk was identified in 1988, very few studies have addressed how Crk regulates the immune response. Recent work demonstrates that Crk proteins function as critical signal molecules in regulating immune cell functions. Emerging data on the roles of Crk in activation and inhibitory immunoreceptor signaling suggest that Crk proteins are potential immunotherapeutic targets in cancer and infectious diseases. The aim of this review is to summarize recent key findings regarding the role of Crk in immune responses mediated by T, B and natural killer (NK) cells. In particular, the roles of Crk in NK cell functions are discussed.
Approaching the strong coupling limit in single plasmonic nanorods interacting with J-aggregates
Authors: Zengin Gülis , Johansson Göran , Johansson Peter , Antosiewicz Tomasz J. , Käll Mikael , Shegai Timur
Published: October 2013

We studied scattering and extinction of individual silver nanorods coupled to the J-aggregate form of the cyanine dye TDBC as a function of plasmon – exciton detuning. The measured single particle spectra exhibited a strongly suppressed scattering and extinction rate at wavelengths corresponding to the J-aggregate absorption band, signaling strong interaction between the localized surface plasmon of the metal core and the exciton of the surrounding molecular shell. In the context of strong coupling theory, the observed “transparency dips” correspond to an average vacuum Rabi splitting of the order of 100 meV, which approaches the plasmon dephasing rate and, thereby, the strong coupling limit for the smallest investigated particles. These findings could pave the way towards ultra-strong light-matter interaction on the nanoscale and active plasmonic devices operating at room temperature.
All‐optical three‐input logic minterms generation using semiconductor optical amplifier‐based Sagnac interferometer
Authors: Lei L. , Da Ros F. , Xu J. , Peucheret C. , Dong J. , Zhang X.
Published: October 2013

All‐optical three‐input logic minterms are generated at 42 Gbit/s with a Sagnac interferometer by using cross‐phase modulation in a semiconductor optical amplifier. To the best of the author's knowledge, this is the first time that high‐speed logic operations with more than two inputs have been experimentally demonstrated in a Sagnac interferometer. Correct and clear temporal waveforms are successfully observed. Bit error ratios and optical signal‐to‐noise ratios are measured to demonstrate the effectiveness of the method. As the basic units of combinational logic operations, logic minterms are promising candidates to construct reconfigurable and programmable logic functions.
Compact quadruple‐mode resonator for wideband bandpass filter design
Authors: Lee Ker Chia , Su Hieng Tiong , Haldar Manas K.
Published: October 2013

This study presents the realisation of a wideband bandpass filter using a novel compact quadruple‐mode resonator. The quadruple‐mode resonator, which is evolved from the square open‐loop resonator, is an interesting structure for a compact design. The resonator has two odd and two even mode resonant frequencies whose approximate analytical expressions are derived. For a wide bandwidth filter, three short branch‐lines are introduced to the resonator in order to widen the separation between the resonant frequencies. A filter with a 3 dB fractional bandwidth of 96.0% is demonstrated. Simulated and measured results are in good agreement.
Electronic structure of carbon dioxide under pressure and insights into the molecular-to-nonmolecular transition
Authors: Shieh Sean R. , Jarrige Ignace , Wu Min , Hiraoka Nozomu , Tse John S. , Mi Zhongying , Kaci Linada , Jiang Jian-Zhong , Cai Yong Q.
Published: October 2013

Significance

In this paper, both oxygen and carbon
K
-edge spectra of CO
2
polymorphs at high pressure and room temperature were reported. The electronic structure of CO
2
shows remarkable change from molecular to nonmolecular transition. Furthermore, a 532-eV feature was observed only at a limited pressure range from ∼37 to 53 GPa, suggesting the presence of a transient species in the nonmolecular phase.
GATA-1 regulates the generation and function of basophils
Authors: Nei Yuichiro , Obata-Ninomiya Kazushige , Tsutsui Hidemitsu , Ishiwata Kenji , Miyasaka Masayuki , Matsumoto Kenji , Nakae Susumu , Kanuka Hirotaka , Inase Naohiko , Karasuyama Hajime
Published: October 2013

Significance

The GATA-1 transcription factor has been extensively characterized and shown to play crucial roles in the development of erythroid cells, magakaryocytes, eosinophils, and mast cells. However, the role of GATA-1 in basophils remained unidentified. We demonstrate that knockdown of Gata1 gene expression in basophils results in impaired cytokine production upon allergen-mediated activation. Moreover, ΔdblGATA mice carrying the mutated Gata1 promoter have reduced numbers of basophils and their progenitors and show impaired responses in basophil-mediated protective immunity against parasitic infections. Thus, GATA-1 plays an important role in both generation and activation of basophils, and ΔdblGATA mice display numerical and functional aberrancy in basophils, in addition to the well-known eosinophil deficiency.
Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks
Authors: Kucyi Aaron , Salomons Tim V. , Davis Karen D.
Published: October 2013

Significance

The mind easily wanders away from mundane tasks, but pain is presumed to automatically capture attention. We demonstrate that individuals differ in how often their minds spontaneously wander away from pain and that these differences are associated with the disruptive effect of pain on cognitive performance. Brain–behavior relationships underscore these individual differences. When people’s minds wander away from pain, there are increased activations of the default mode network (DMN) and strong interactions between the DMN and periaqueductal gray (PAG), an opiate-rich region mediating pain suppression. Individuals with greater tendencies to mind wander from pain have stronger anatomical links and dynamic functional communication between PAG and DMN. These findings provide clinically important clues about why some individuals cannot disengage from pain.
Substrate protein switches GroE chaperonins from asymmetric to symmetric cycling by catalyzing nucleotide exchange
Authors: Ye Xiang , Lorimer George H.
Published: October 2013

Significance

Kinetic analyses of the GroEL/GroES chaperonin nanomachine using multiple spectroscopic probes shows that without substrate protein, the two GroEL rings function alternately, 180° out of phase with one another, via an asymmetric cycle. The rate-determining step is the dissociation of the product ADP and the predominant species is the asymmetric “bullet” GroEL-GroES
1
. With substrate protein present, a change in the kinetic mechanism occurs. The two rings now function simultaneously via a symmetric cycle in which ATP hydrolysis becomes the rate-limiting step, ADP/ATP exchange is catalyzed by substrate protein and the predominant species is the symmetric “football” GroEL-GroES
2
.
Yeast metabolic and signaling genes are required for heat-shock survival and have little overlap with the heat-induced genes
Authors: Gibney Patrick A. , Lu Charles , Caudy Amy A. , Hess David C. , Botstein David
Published: October 2013

Significance

We used the model eukaryote
Saccharomyces cerevisiae
to investigate which genes are important for survival of heat stress. Previously, this question was addressed by examining which genes are turned on by mild heat stress; in this study, we examined gene-deletion mutants for increased sensitivity to lethal heat stress. This approach reveals that these two sets of genes are largely nonoverlapping, demonstrating that mutant analysis is a powerful complementary approach to gene-expression analysis. In addition, many of the genes identified as important for heat survival are involved in metabolism or signaling, or their function is completely uncharacterized, suggesting that our understanding of the systems-level response to heat stress is incomplete.
La Revanche du flou: Jacques Réda à l'épreuve de la cartographie dans
Le MéRidien de Paris
Authors: Duclos Jean-François Rémy
Published: October 2013

En 1994, le plasticien néerlandais Jan Dibbets a, pour rendre hommage au physicien François Arago, installé sur le sol de Paris plus d'une centaine de médaillons de bronze qui forment en pointillés le tracé d'un méridien.
Le Méridien de Paris
de Jacques Réda, publié peu de temps plus tard, se présente comme le journal d'un spectateur qui a décidé de suivre cette ligne dans l'espoir que, sous l'effet d'une telle contrainte spatiale, quelque chose de non-programmé advienne à l'écriture. Or ce texte montre que la matérialisation de la ligne de longitude, issue d'un calcul géodésique rigoureux, répond tout autant aux injonctions du hasard en faussant régulièrement compagnie à celui qui souhaite la suivre. La ligne droite semble aller de guingois. Sans recul ni horizon pour maintenir l'illusion d'une distance, le piéton doit, tel l'arpenteur, passer par la mesure cartographique et dépasser sa littéralité. L'hommage de Dibbets, anti-monument par excellence, constitue une fiction à peine repérable de l'invisible géographique. Pour Réda, il finit par former une méthode qui fournira à son écriture le flou dont elle a besoin pour se déployer. Ainsi le ‘système Dibbets’ devient un art d'écrire selon une métrique qui autorise la syncope et le pas de côté.
Shade Tree Spatial Structure and Pod Production Explain Frosty Pod Rot Intensity in Cacao Agroforests, Costa Rica
Authors: Gidoin Cynthia , Avelino Jacques , Deheuvels Olivier , Cilas Christian , Bieng Marie Ange Ngo
Published: October 2013

Vegetation composition and plant spatial structure affect disease intensity through resource and microclimatic variation effects. The aim of this study was to evaluate the independent effect and relative importance of host composition and plant spatial structure variables in explaining disease intensity at the plot scale. For that purpose, frosty pod rot intensity, a disease caused by Moniliophthora roreri on cacao pods, was monitored in 36 cacao agroforests in Costa Rica in order to assess the vegetation composition and spatial structure variables conducive to the disease. Hierarchical partitioning was used to identify the most causal factors. Firstly, pod production, cacao tree density and shade tree spatial structure had significant independent effects on disease intensity. In our case study, the amount of susceptible tissue was the most relevant host composition variable for explaining disease intensity by resource dilution. Indeed, cacao tree density probably affected disease intensity more by the creation of self-shading rather than by host dilution. Lastly, only regularly distributed forest trees, and not aggregated or randomly distributed forest trees, reduced disease intensity in comparison to plots with a low forest tree density. A regular spatial structure is probably crucial to the creation of moderate and uniform shade as recommended for frosty pod rot management. As pod production is an important service expected from these agroforests, shade tree spatial structure may be a lever for integrated management of frosty pod rot in cacao agroforests.
Social competition and selection in males and females
Authors: Clutton-Brock T. H. , Huchard E.
Published: October 2013

During the latter half of the last century, evidence of reproductive competition between males and male selection by females led to the development of a stereotypical view of sex differences that characterized males as competitive and aggressive, and females as passive and choosy, which is currently being revised. Here, we compare social competition and its consequences for selection in males and females and argue that similar selection processes operate in both sexes and that contrasts between the sexes are quantitative rather than qualitative. We suggest that classifications of selection based on distinction between the form of competition or the components of fitness that are involved introduce unnecessary complexities and that the most useful approach in understanding the evolution and distribution of differences and similarities between the sexes is to compare the operation of selection in males and females in different reproductive systems.
Reproductive competition between females in the matrilineal Mosuo of southwestern China
Authors: Ji Ting , Wu Jia-Jia , He Qiao-Qiao , Xu Jing-Jing , Mace Ruth , Tao Yi
Published: October 2013

The matrilineal Mosuo of southwestern China live in communal households where brothers and sisters of three generations live together (duolocal residence), and men visit their wives, who reside elsewhere, only at night in ‘visiting’ marriages. Here we show that these communally breeding sisters are in reproductive conflict, in the sense that they share the resources needed to reproduce. We analyse determinants of reproductive success in females and males, and show that co-resident female kin are in competition; the more female kin reside in the household, the more reproductive success is reduced. Male reproductive success, however, is not determined by the kin in his natal household; duolocal males are not in reproductive conflict with their siblings. Competition with female cousins can be worse than that between sisters. We also find that female work on the farm (which is the main communal resource) is not equal. We use a ‘tug-of-war’ model of reproductive skew generated by incomplete control, to model the patterns of effort put into competition between sisters and cousins. The model predicts that more dominant (older) sisters will put less effort into reproductive conflict than will less dominant (younger) sisters; but younger sisters will also have lower reproductive success because they are less efficient at gaining access to the shared resource. Both predictions are consistent with our data. Younger sisters work less in the fields than do older sisters, which may represent a form of conflict or may be because their average relatedness to the household is lower than that of their more fertile older sisters.
The influence of androgenic steroid hormones on female aggression in ‘atypical’ mammals
Authors: French Jeffrey A. , Mustoe Aaryn C. , Cavanaugh Jon , Birnie Andrew K.
Published: October 2013

Dimorphism on dominance and agonistic behaviour in mammals tends to be strongly biased toward males. In this review, we focus on a select few species of mammals in which females are as or more aggressive than males, and/or are dominant to males, and explore the role of androgenic hormones in mediating this important difference. While the data are not as clear-cut as those published on traditional laboratory mammals, our review highlights important endocrine substrates for both organizational and activational influences of steroids on female aggressive behaviour. We highlight areas in which further observations and experiments are crucial, especially the potential facilitative effects of androgens on female aggression. Finally, new and innovative techniques, including molecular genetics and receptor pharmacology, portend important insights into the ways in which androgenic hormones regulate aggressive behaviour in ‘atypical’ female mammals.
A new laboratory technique for determining the compressional wave properties of marine sediments at sonic frequencies and in situ pressures
Authors: McCann Clive , Sothcott Jeremy , Best Angus I.
Published: October 2013

We describe a new laboratory technique for measuring the compressional wave velocity and attenuation of jacketed samples of unconsolidated marine sediments within the acoustic (sonic) frequency range 1–10 kHz and at elevated differential (confining – pore) pressures up to 2.413 MPa (350 psi). The method is particularly well suited to attenuation studies because the large sample length (up to 0.6 m long, diameter 0.069 m) is equivalent to about one wavelength, thus giving representative bulk values for heterogeneous samples. Placing a sediment sample in a water‐filled, thick‐walled, stainless steel Pulse Tube causes the spectrum of a broadband acoustic pulse to be modified into a decaying series of maxima and minima, from which the Stoneley and compressional wave, velocity and attenuation of the sample can be determined. Experiments show that PVC and copper jackets have a negligible effect on the measured values of sediment velocity and attenuation, which are accurate to better than ± 1.5% for velocity and up to ± 5% for attenuation. Pulse Tube velocity and attenuation values for sand and silty‐clay samples agree well with published data for similar sediments, adjusted for pressure, temperature, salinity and frequency using standard equations. Attenuation in sand decreases with pressure to small values below Q−1 = 0.01 (Q greater than 100) for differential pressures over 1.5 MPa, equivalent to sub‐seafloor depths of about 150 m. By contrast, attenuation in silty clay shows little pressure dependence and intermediate Q−1 values between 0.0206–0.0235 (Q = 49–43). The attenuation results fill a notable gap in the grain size range of published data sets. Overall, we show that the Pulse Tube method gives reliable acoustic velocity and attenuation results for typical marine sediments.
The Effect of mGluR5 Antagonism During Binge Drinking on Subsequent Ethanol Intake in C57BL/6J Mice: Sex‐ and Age‐Induced Differences
Authors: Cozzoli Debra K. , Strong‐Kaufman Moriah N. , Tanchuck Michelle A. , Hashimoto Joel G. , Wiren Kristine M. , Finn Deborah A.
Published: October 2013

Background

Binge ethanol (EtOH) intake during adolescence leads to an array of behavioral and cognitive consequences including elevated intake of EtOH during adulthood, with female mice showing greater susceptibility than males. Administration of the metabotropic glutamate receptor 5 (mGluR5) antagonist 3‐((2‐Methyl‐1,3‐thiazol‐4‐yl)ethynyl)pyridine (MTEP) has been shown to reduce EtOH self‐administration in adult male mice, but little is known about its effect on female and adolescent mice.

Methods

MTEP (0, 10, 20 mg/kg, i.p.) was repeatedly administered to female and male, adult and adolescent C57BL/6J mice during binge sessions using the scheduled high alcohol consumption paradigm. Next, we assessed whether MTEP administration during binge altered the subsequent 24‐hour EtOH intake following a period of abstinence. Finally, we investigated whether MTEP administration during binge followed by an abstinence period altered mRNA of glutamatergic genes within the nucleus accumbens of female mice.

Results

MTEP significantly decreased binge EtOH intake in all mice, but only female mice exhibited altered subsequent 24‐hour EtOH intake. Interestingly, the alteration in subsequent EtOH intake in female animals was age dependent, with adolescent exposure to MTEP during binge decreasing 24‐hour intake and adult exposure to MTEP during binge increasing 24‐hour intake. Finally, while there were no effects of MTEP pretreatment on the genes examined, there was a robust age effect found during analysis of mGluR1 (Grm1), mGluR5 (Grm5), the NR2A subunit of the NMDA receptor (Grin2a), phosphatidylinositol 3‐kinase (Pik3r1), mammalian target of rapamycin (Mtor), and extracellular signal‐regulated kinase (Mapk1) mRNA, with adolescent female animals having lower expression than their adult counterparts.

Conclusions

Collectively, the present findings add to existing evidence implicating the contribution of long‐term effects of adolescent binge drinking to enhance alcohol abuse in adulthood, while suggesting that mGluR5 antagonism may not be the best pharmacotherapy to treat binge alcohol consumption in female and adolescent animals.
Formulations for children: problems and solutions
Authors: Batchelor Hannah K. , Marriott John F.
Published: October 2013

Paediatric formulation design is complex as there is a need to understand the developmental physiological changes that occur during childhood and their impact on the absorption of drugs. Paediatric dose adjustments are usually based on achieving pharmacokinetic or pharmacodynamic profiles equivalent to those achieved in adult populations. However, differences in the way in which children handle adult products or the use of bespoke paediatric formulations can result in unexpected pharmacokinetic drug profiles with altered clinical efficacy. Differences in drug formulations need to be understood by healthcare professionals involved in the prescribing, administration or dispensing of drugs to children such that appropriate advice is given to ensure that therapeutic outcomes are achieved. This issue is not confined to oral medicines but is applicable for all routes of administration encountered in paediatric therapy.
Biological effects of blocking blue and other visible light on the mouse retina
Authors: Narimatsu Toshio , Ozawa Yoko , Miyake Seiji , Kubota Shunsuke , Yuki Kenya , Nagai Norihiro , Tsubota Kazuo
Published: October 2013

Background

To elucidate the biological effects of blocking fluorescent light on the retina using specific blocking materials.

Methods

Seven‐ to 8‐week‐old BALB/c mice were divided into three groups and placed in one of the three boxes: one blocked ultraviolet and violet wavelengths of light (violet blockade), one blocked ultraviolet, violet, blue and some other visible wavelengths (blue‐plus blockade), and one allowed most visible light to pass through (control). They were then exposed to a white fluorescent lamp for 1 h at 5.65E‐05 mW/cm2/s. After treatment, the electroretinogram, retinal outer nuclear layer thickness and retinal outer segment length were measured. In addition, retinal apoptotic cells were quantified by TdT‐mediated dUTP nick‐end labelling assay and c‐Fos messenger RNA, and protein levels were measured by real‐time reverse‐transcription polymerase chain reaction and immunoblot analyses, respectively.

Results

The blue‐plus blockade group retained a significantly better electroretinogram response following light exposure than the control or violet blockade groups. The blue‐plus blockade group also exhibited greater outer nuclear layer thickness and greater outer‐segment length, and fewer apoptotic cells after light exposure than the other groups. The c‐Fos messenger RNA and protein levels were substantially reduced in the blue‐plus blockade group and reduced to a lesser extent in the violet blockade group.

Conclusions

The blockade of blue plus additional visible wavelengths of light was most effective in protecting the retina from light‐induced damage. The blockade of violet light alone was also effective in reducing intracellular molecular responses, but these effects were not sufficient for attenuating retinal degeneration.
Sense‐making in a social work office: an ethnographic study of safeguarding judgements
Authors: Helm Duncan
Published: October 2013

Social workers are routinely required to make finely balanced judgements on matters defined by subjectivity and uncertainty. Often, these judgements have to be made on the basis of information which is incomplete, inconclusive and contested. The way in which social workers make sense of such information is a crucial component of effective assessment and intervention. This ethnographic study of judgements in a social work office describes some of the practices which practitioners employed in making sense of information about children and young people's needs. The findings suggest that initial statements in dialogue may potentially act as signposts for preceding intuitive sense‐making. Observations offer insights into the way in which individuals construct professional responsibility. The study also suggests that sense‐making is not necessarily an individual activity but can be an activity which is shared between people and across teams. The findings indicate the importance of emotional intelligence and intersubjectivity in social work judgements.
Role of histone deacetylases in regulation of phenotype of ovine newborn pulmonary arterial smooth muscle cells
Authors: Yang Q. , Dahl M. J. , Albertine K. H. , Ramchandran R. , Sun M. , Raj J. U.
Published: October 2013

Objective

Pulmonary arterial hypertension, characterized by pulmonary vascular remodelling and vasoconstriction, is associated with excessive proliferative changes in pulmonary vascular walls. However, the role of HDACs in the phenotypic alteration of pulmonary arterial smooth muscle cells (PASMC) is largely unknown.

Material and methods

Pulmonary arterial smooth muscle cells were isolated from newborn sheep. Cell cycle analysis was performed by flow cytometry. mRNA and protein expression were measured by real‐time PCR and Western blot analysis. Wound‐healing scratch assay was used to measure cell migration. Contractility of newborn PASMCs was determined by gel contraction assay. Chromatin immunoprecipitation was used to examine histone modifications along the p21 promoter region. Global DNA methylation was measured by liquid chromatography‐mass spectroscopy.

Results

Inhibition of class I and class II HDACs by apicidin and HDACi VIII suppressed proliferation of newborn PASMC and induced cell cycle arrest in G1 phase. Acetyl H3 levels were higher in newborn PASMC treated with apicidin and HDACi VIII. This was accompanied by increased expression of p21 and reduced expression of CCND1 but not p53. HDAC inhibition altered histone codes around the p21 promoter region in NPASMC. Apicidin inhibited serum‐induced cell migration, and modulated profiling of expression of genes encoding pro‐oxidant and antioxidant enzymes. Contractility and global DNA methylation levels of newborn PASMCs were also markedly modulated by apicidin.

Conclusion

Our results demonstrate that class I HDACs are clearly involved in phenotypic alteration of newborn PASMC.
Serum leptin, adiponectin, and resistin among adult patients with acanthosis nigricans: correlations with insulin resistance and risk factors for cardiovascular disease
Authors: Atwa Mona , Emara Amany , Balata Mona , Youssef Nahed , Bayoumy Nervana , Sherif Abdulsalam , Fiala Lamia
Published: October 2013

Background

Acanthosis nigricans (AN) is linked to obesity and insulin resistance. Major adipokines such as leptin, adiponectin, and resistin are known to be dysregulated in obesity and are key players in the pathogenesis of metabolic syndrome.

Objectives

This study was conducted to assess serum levels of the major adipokines leptin, adiponectin, and resistin, and to study their correlations with the state of insulin resistance and other risk factors for cardiovascular disease (CVD) among AN patients.

Methods

A total of 115 adult subjects were included in the study; 52 of these had benign acquired AN, and 63 (control subjects) were without AN. Thirty‐three of the control group were obese, and 30 were healthy subjects of normal weight. Body mass index (BMI), blood pressure, lipid profile, fasting blood glucose, fasting insulin, serum leptin, adiponectin, and resistin were assessed in all subjects.

Results

We found significant differences between AN patients and obese controls in serum levels of leptin (30.02 ± 15.14 ng/ml vs. 21.07 ± 7.92 ng/ml; P = 0.002), adiponectin (5.55 ± 2.89 μg/l vs. 9.02 ± 2.33 μg/ml; P = 0.00001), and resistin (20.88 ± 3.97 ng/ml vs. 16.82 ± 4.36 ng/ml; P = 0.00003). Significant positive correlations were found between serum leptin and homeostasis model assessment (HOMA) value, insulin, glucose, BMI, cholesterol, and low‐density lipoprotein. There were also significant negative correlations between adiponectin and HOMA value, insulin, BMI, cholesterol, and leptin among AN patients.

Conclusions

Acanthosis nigricans is a likely forerunner of the finding of metabolic syndrome. High serum leptin and resistin and low serum adiponectin may increase the risk for CVD among AN patients.
Protein leverage and energy intake
Authors: Gosby A. K. , Conigrave A. D. , Raubenheimer D. , Simpson S. J.
Published: October 2013

Increased energy intakes are contributing to overweight and obesity. Growing evidence supports the role of protein appetite in driving excess intake when dietary protein is diluted (the protein leverage hypothesis). Understanding the interactions between dietary macronutrient balance and nutrient‐specific appetite systems will be required for designing dietary interventions that work with, rather than against, basic regulatory physiology. Data were collected from 38 published experimental trials measuringad libitumintake in subjects confined to menus differing in macronutrient composition. Collectively, these trials encompassed considerable variation in percent protein (spanning 8–54% of total energy), carbohydrate (1.6–72%) and fat (11–66%). The data provide an opportunity to describe the individual and interactive effects of dietary protein, carbohydrate and fat on the control of total energy intake. Percent dietary protein was negatively associated with total energy intake (F = 6.9,P < 0.0001) irrespective of whether carbohydrate (F = 0,P = 0.7) or fat (F = 0,P = 0.5) were the diluents of protein. The analysis strongly supports a role for protein leverage in lean, overweight and obese humans. A better appreciation of the targets and regulatory priorities for protein, carbohydrate and fat intake will inform the design of effective and health‐promoting weight loss diets, food labelling policies, food production systems and regulatory frameworks.
Reproductive biology and pollination of Utricularia reniformis A.St.‐Hil. (Lentibulariaceae)
Authors: Clivati D. , Cordeiro G. D. , Płachno B. J. , de Miranda V. F. O.
Published: October 2013

Utricularia reniformis is an endemic Brazilian carnivorous plant, most common in high‐altitude grasslands. Knowledge of the reproductive biology of U. reniformis is essential for planning conservation strategies, but it is currently poorly understood. Thus, we studied the floral morphology, floral biology, breeding system and pollination of this species. U. reniformis produces and stores nectar in the flower spur, a classic feature of bee‐pollinated flowers, and we recorded Xylocopa sp. and Bombus sp. as pollinators. Moreover, although it is self‐compatible it is an obligate animal‐pollinated species, as the sensitive stigma avoids self‐pollination. However, in natural conditions reproductive success is low due to the rarity of visits from pollinators. We suggest that the low reproductive success caused by a deficit of pollinators may affect gene flow, causing loss of genetic diversity in U. reniformis.
Structure and function of CrACA1, the major PM‐type Ca2+‐ATPase, expressed at the peak of the gravity‐directed trans‐cell calcium current in spores of the fern Ceratopteris richardii
Authors: Bushart T. J. , Cannon A. , Clark G. , Roux S. J.
Published: October 2013

Spores of the fern Ceratopteris richardii have proven to be a valuable single‐cell system for studying gravity responses. The earliest cellular change directed by gravity in these cells is a trans‐cell calcium current, which peaks near 10 h after the spores are induced to germinate. This current is needed for gravity‐directed axis alignment, and its peak is coincident with the time period when gravity polarises the direction of subsequent nuclear migration and rhizoid growth. Transcriptomic analysis of genes expressed at the 10‐h time point revealed several that encode proteins likely to be key components that either drive the current or regulate it. Notable among these is a plasma membrane (PM)‐type Ca2+ATPase, CrACA1, whose activity pumping Ca2+ out of cells is regulated by gravity. This report provides an initial characterisation of the structure and expression of this protein, and demonstrates its heterologous function complementing the K616 mutant of yeast, which is deficient in PM‐type Ca2+ pump activity. Gravity‐induced changes in the trans‐cell Ca2+ current occur within seconds, a result consistent with the hypothesis that the force of gravity can rapidly alter the post‐translational state of the channels and pumps that drive this current across spore cells. This report identifies a transporter likely to be a key driver of the current, CrACA1, and characterises the role of this protein in early germination and gravity‐driven polarity fixation through analysis of expression levels, functional complementation and pharmacological treatments. These data, along with newly available transcriptomic data obtained at the 10‐h time point, indicate that CrACA1 is present, functional and likely a major contributing component of the trans‐cell Ca2+ efflux. CrACA1 is not necessary for polar axis alignment, but pharmacological perturbations of it disrupt rhizoid development. These data support and help refine the post‐translational modification model for gravity responses.
Phytophthora acerina sp. nov., a new species causing bleeding cankers and dieback of Acer pseudoplatanus trees in planted forests in northern Italy
Authors: Ginetti B. , Moricca S. , Squires J. N. , Cooke D. E. L. , Ragazzi A. , Jung T.
Published: October 2013

A severe dieback of Acer pseudoplatanus trees was noticed in planted forest stands in northern Italy in 2010. Affected trees showed collar rot and aerial bleeding cankers along the stems, leading to crown dieback and eventually death. An unknown Phytophthora species was consistently isolated from necrotic bark and xylem tissue and from rhizosphere soil. Based on its unique combination of morphological and physiological characters and phylogenetic analysis, this new taxon is here described as Phytophthora acerina sp. nov. Phylogenetic analysis of ITS, cox1 and β‐tubulin gene regions demonstrated that P. acerina is unique and forms a separate cluster within the ‘P. citricola complex’, closely related to P. plurivora. Phytophthora acerina is homothallic with smooth‐walled oogonia, thick‐walled, mostly aplerotic oospores with a high abortion rate, paragynous antheridia, and persistent, morphologically variable semipapillate sporangia. Four to 5‐week‐old cultures produced globose to subglobose, appressoria‐like and coralloid hyphal swellings and characteristic stromata‐like hyphal aggregations. Optimum and maximum temperatures for growth are 25°C and 32°C, respectively. Genetic uniformity of all 15 studied isolates and the apparent absence of this species in the extensive surveys of nurseries, forests and seminatural ecosystems conducted in the previous two decades across Europe indicate a recent clonal introduction to northern Italy. Under‐bark inoculation tests demonstrated high aggressiveness of P. acerina to A. pseudoplatanus indicating that this pathogen might be a serious risk to maple plantations and forests in Europe.
A Family of Rotational Parallel Manipulators With Equal-Diameter Spherical Pure Rotation
Authors: Wu Kang , Yu Jingjun , Zong Guanghua , Kong Xianwen
Published: October 2013

In this work, a family of two degrees of freedom (2-DOF) rotational parallel manipulators (RPMs) with an equal-diameter spherical pure rotation (ESPR) is presented and discussed systematically. The theoretical models of both kinematics and constraints inherited in the manipulators are analyzed through a graphical approach. Based on the established constraint model, these 2-DOF ESPR RPMs are classified into three types according to their compositions of constraint spaces and several novel parallel manipulators are illustrated correspondingly. Finally, two common necessary geometric conditions satisfied for these manipulators are discussed in details with examples. The two conditions will be helpful for engineers with designing ESPR RPMs. Moreover, as one characteristic existing in the ESPR RPMs, two cases of self-rotations accompanying revolutions around fixed axes are revealed. As a result, the corresponding loci of points in the moving platform are proved to be compositions of two subrotations, which are spatial curves and surfaces rather than spherical curves and surfaces.
Antibiotic Resistance Genes in the Bacteriophage DNA Fraction of Human Fecal Samples
Authors: Quirós Pablo , Colomer-Lluch Marta , Martínez-Castillo Alexandre , Miró Elisenda , Argente Marc , Jofre Juan , Navarro Ferran , Muniesa Maite
Published: October 2013

A group of antibiotic resistance genes (ARGs) (
bla
TEM
,
bla
CTX-M-1
,
mecA
,
armA
,
qnrA
, and
qnrS
) were analyzed by real-time quantitative PCR (qPCR) in bacteriophage DNA isolated from feces from 80 healthy humans. Seventy-seven percent of the samples were positive in phage DNA for one or more ARGs.
bla
TEM
,
qnrA
, and,
bla
CTX-M-1
were the most abundant, and
armA
,
qnrS
, and
mecA
were less prevalent. Free bacteriophages carrying ARGs may contribute to the mobilization of ARGs in intra- and extraintestinal environments.
Stressing the Development of Small Molecules Targeting HSP90
Authors: Neckers Len , Trepel Jane B.
Published: October 2013

Inhibitors of the molecular chaperone HSP90 have been in clinical development as anticancer agents since 1999. Recent clinical studies, including the work of Saif and colleagues in this issue of Clinical Cancer Research, demonstrate that significant progress has been made in overcoming the obstacles preventing regulatory approval. Clin Cancer Res; 20(2); 275–7. ©2013 AACR.