bluuebunny/crossref_metadata_2025 huggingface dataset:
HomoKult
Authors: Akbari Alireza , Shahnazari Mohammadtaghi
Published: September 2014

In New Translation Studies (NTS), cultural paradigm is of great importance to convey the approximate function of the source language into the target language context. Paradigm of culture is treated differently in accordance with its different definitions in that most of the studies carried out in this field show cultural diversification as the basic and rudimental part of this paradigm. In Translation Studies, the translator has to do with two kinds of situations so as to transmit the meaning and function of the culture. The first one is known as cultural diversification and the second one as cultural hybridity or homogenization. The former is aimed at Old Translation Studies era, which investigates source–target dispersion. And the latter alludes to source–target reconciliation. The present study seeks to investigate some void areas in translation and culture and proposes a new model in which it makes some efforts to reconcile translation and culture via cultural homogenization known as HomoKult Model of Translation in Gray Zone. The intended process consists of four subcategories: (a) Purposive culture, (b) Ameliorated culture, (c) Circulated culture, and (d) Diglossic culture expounded in detail throughout this article.
Attitude Formation Through Exploration
Authors: Jones Christopher R. , Eiser J. Richard
Published: September 2014

Little experimental research has investigated how attitudes are formed via direct personal experience within risky environments. This report summarizes the development of Treasure Island (TI), an attitude learning paradigm based on BeanFest. Two studies are reported: The first designed to compare the outcomes of TI with BeanFest; the second to show how a manipulation of risk predictability would affect attitude learning within the paradigm. Study 1 demonstrated sampling and learning asymmetries similar to those seen in BeanFest, although the magnitude of these asymmetries was attenuated by the opportunity for participants to landmark decisions. The manipulation of risk predictability in Study 2 led participants to seemingly form a less accurate representation of the underlying pay-off contingencies; however, a significant negative learning asymmetry did persist. The findings of this research (a) identify TI as a versatile paradigm for the investigation of attitude learning within risky environments and (b) confirm the robust nature of the negative learning asymmetry in contingent-learning settings; but (c) assert that care should be taken when generalizing the findings of BeanFest to ostensibly more variable contexts.
Weldability and mechanical properties of similar and dissimilar resistance spot welds of three-layer advanced high strength steels
Authors: Wei S. T. , Liu R. D. , Lv D. , Lin L. , Xu R. J. , Guo J. Y. , Wang K. Q. , Lu X. F.
Published: September 2014

Similar and dissimilar combinations of a 1000 MPa galvanised dual phase (DP) steel, a 980 MPa transformation induced plasticity (TRIP) steel and a 980 MPa twinning induced plasticity (TWIP) steel were resistance spot welded under different welding parameters. The macrostructure, splash situation, nugget size and mechanical properties of the spot welds were evaluated systematically. The results showed that the different heat conductivities, melting points and surface electric resistances of the DP, TRIP and TWIP steels resulted in the asymmetric weld nuggets of the dissimilar spot welds and the increase in the splash occurring current in order of DP/DP/DP, TRIP/DP/TWIP, TWIP/TRIP/DP, TRIP/TWIP/DP (TRIP/TRIP/TRIP), TWIP/TRIP/DP and TWIP/TWIP/TWIP. For the dissimilar spot welding of galvanised DP1000, uncoated TRIP980 and uncoated TWIP980, the TRIP/TWIP/DP combination can obtain better weld quality than the TRIP/DP/TWIP and TWIP/TRIP/DP combinations.
Titanium alloy developments for aeroengine fan systems
Authors: Hewitt J. S. , Davies P. D. , Thomas M. J. , Garratt P. , Bache M. R.
Published: September 2014

Recent research relating to two α+β processed titanium alloys, designed for specific employment in aeroengine fan disc and aerofoil components, is described. Timetal 575 (Ti575) and Timetal 639 (Ti639) are both novel compositions that provide relatively high strength compared to Ti–6Al–4V. Static and cyclic behaviour of the two developmental alloys were evaluated at room temperature. A dwell fatigue assessment of Ti575 is reported, while the effects of unidirectional rolling and associated evolution of microtexture were studied for Ti639.
Electroless Ni–W–Cr–P alloy coating with improved electrocatalytic hydrogen evolution performance
Authors: Wang H. , Xie M. , Zong Q. , Liu Z. , Huang X. , Jin Y.
Published: September 2014

The quaternary Ni–W–Cr–P alloy coatings were deposited on copper alloy by an electroless deposition process. Micromorphology, microstructure and hydrogen evolution reaction (HER) activity of electroless Ni–W–Cr–P coatings were examined. X-ray diffraction analysis showed that the Ni–W–Cr–P coatings were solid solution, and crystallisation started to occur with increasing heat treatment temperature. The experimental results also revealed that HER activity of the Ni–W–Cr–P coatings was enhanced compared with those of the uncoated. Moreover, with increasing annealing temperature, HER activity of the Ni–W–Cr–P coatings varied slightly. When heated at 500°C, the electrode got the best Tafel slope of 144 mV/decade and quite small overpotentials of 354 and 479 mV at the current densities of 10 and 30 mA cm−2 respectively. Electroless deposition is a good way to get alloy coating, which can improve the electrocatalytic activity of the hydrogen generation efficiently.
HMGA1 and HMGA2 expression and comparative analyses of HMGA2, Lin28and let-7 miRNAs in oral squamous cell carcinoma
Authors: Sterenczak Katharina Anna , Eckardt Andre , Kampmann Andreas , Willenbrock Saskia , Eberle Nina , Länger Florian , Kleinschmidt Sven , Hewicker-Trautwein Marion , Kreipe Hans , Nolte Ingo , Escobar Hugo Murua , Gellrich Nils Claudius
Published: September 2014

Background

Humans and dogs are affected by squamous cell carcinomas of the oral cavity (OSCC) in a considerably high frequency. The high mobility group A2 (HMGA2) protein was found to be highly expressed in human OSCC and its expression was suggested to act as a useful predictive and prognostic tool in clinical management of oral carcinomas. Herein the expression of HMGA2 and its sister gene HMGA1 were analysed within human and canine OSCC samples. Additionally, the HMGA negatively regulating miRNAs of the let-7 family as well as the let-7 regulating gene Lin28 were also comparatively analysed. Deregulations of either one of these members could affect the progression of human and canine OSCC.

Methods

Expression levels of HMGA1, HMGA2, Lin28, let-7a and mir-98 were analysed via relative qPCR in primary human and canine OSCC, thereof derived cell lines and non-neoplastic samples. Additionally, comparative HMGA2 protein expression was analysed by immunohistochemistry.

Results

In both species, a significant up-regulation of the HMGA2 gene was found within the neoplastic samples while HMGA1 expression did not show significant deregulations. Comparative analyses showed down-regulation of mir-98 in human samples and up-regulation of let-7a and mir-98 in canine neoplastic samples. HMGA2 immunostainings showed higher intensities within the invasive front of the tumours than in the centre of the tumour in both species.

Conclusions

HMGA2 could potentially serve as tumour marker in both species while HMGA1 might play a minor role in OSCC progression. Comparative studies indicate an inverse correlation of HMGA2 and mir-98 expression in human samples whereas in dogs no such characteristic could be found.
Sustained Pain-Related Depression of Behavior: Effects of Intraplantar Formalin and Complete Freund's Adjuvant on Intracranial Self-Stimulation (ICSS) and Endogenous kappa Opioid Biomarkers in Rats
Authors: Leitl Michael D , Potter David N , Cheng Kejun , Rice Kenner C , Carlezon William A , Negus S Stevens
Published: September 2014

Background:

Intraplantar administration of complete Freund's adjuvant (CFA) and formalin are two noxious stimuli commonly used to produce sustained pain-related behaviors in rodents for research on neurobiology and treatment of pain. One clinically relevant manifestation of pain is depression of behavior and mood. This study compared effects of intraplantar CFA and formalin on depression of positively reinforced operant behavior in an assay of intracranial self-stimulation (ICSS) in rats. Effects of CFA and formalin on other physiological and behavioral measures, and opioid effects on formalin-induced depression of ICSS, were also examined.

Results:

There were four main findings. First, consistent with previous studies, both CFA and formalin produced similar paw swelling and mechanical hypersensitivity. Second, CFA produced weak and transient depression of ICSS, whereas formalin produced a more robust and sustained depression of ICSS that lasted at least 14 days. Third, formalin-induced depression of ICSS was reversed by morphine doses that did not significantly alter ICSS in saline-treated rats, suggesting that formalin effects on ICSS can be interpreted as an example of pain-related and analgesic-reversible depression of behavior. Finally, formalin-induced depression of ICSS was not associated with changes in central biomarkers for activation of endogenous kappa opioid systems, which have been implicated in depressive-like states in rodents, nor was it blocked by the kappa antagonist norbinaltorphimine.

Conclusions:

These results suggest differential efficacy of sustained pain stimuli to depress brain reward function in rats as assessed with ICSS. Formalin-induced depression of ICSS does not appear to engage brain kappa opioid systems.
Risks to emergency medical responders at terrorist incidents: a narrative review of the medical literature
Authors: Thompson Julian , Rehn Marius , Lossius Hans Morten , Lockey David
Published: September 2014

As the threat of international terrorism rises, there is an increasing requirement to provide evidence-based information and training for the emergency personnel who will respond to terrorist incidents. Current major incident training advises that emergency responders prioritize their own personal safety above that of the `scene and survivors’. However, there is limited information available on the nature of these threats and how they may be accurately evaluated. This study reviews the published medical literature to identify the hazards experienced by emergency responders who have attended previous terrorist incidents. A PubMed literature search identified 10,894 articles on the subject of `terrorism’, and there was a dramatic increase in publications after the 9/11 attacks in 2001. There is heterogeneity in the focus and quality of this literature, and 307 articles addressing the subject of scene safety were assessed for information regarding the threats encountered at terrorist incidents. These articles demonstrate that emergency responders have been exposed to both direct terrorist threats and environmental scene hazards, including airborne particles, structural collapse, fire, and psychological stress. The emphasis of training and preparedness for terrorist incidents has been primarily on the direct threats, but the published literature suggests that the dominant causes of mortality and morbidity in responders after such incidents are the indirect environmental hazards. If the medical response to terrorist incidents is to be based on evidence rather than anecdote, analysis of the current literature should be incorporated into major incident training, and consistent collection of key data from future incidents is required.
An optimal transition time to extracorporeal cardiopulmonary resuscitation for predicting good neurological outcome in patients with out-of-hospital cardiac arrest: a propensity-matched study
Authors: Kim Su Jin , Jung Jae Seung , Park Jae Hyoung , Park Jong Su , Hong Yun Sik , Lee Sung Woo
Published: September 2014

Introduction

Prolonged conventional cardiopulmonary resuscitation (CCPR) is associated with a poor prognosis in out-of-hospital cardiac arrest (OHCA) patients. Alternative methods can be needed to improve the outcome in patients with prolonged CCPR and extracorporeal cardiopulmonary resuscitation (ECPR) can be considered as an alternative method. The objectives of this study were to estimate the optimal duration of CPR to consider ECPR as an alternative resuscitation method in patients with CCPR, and to find the indications for predicting good neurologic outcome in OHCA patients who received ECPR.

Methods

This study is a retrospective analysis based on a prospective cohort. We included patients ≥18 years of age without suspected or confirmed trauma and who experienced an OHCA from May 2006 to December 2013. First, we determined the appropriate cut-off duration for CPR based on the discrimination of good and poor neurological outcomes in the patients who received only CCPR, and then we compared the outcome between the CCPR group and ECPR group by using propensity score matching. Second, we compared CPR related data according to the neurologic outcome in matched ECPR group.

Results

Of 499 patients suitable for inclusion, 444 and 55 patients were enrolled in the CCPR and ECPR group, respectively. The predicted duration for a favorable neurologic outcome (CPC1, 2) is < 21 minutes of CPR in only CCPR patients. The matched ECPR group with ≥21 minutes of CPR duration had a more favorable neurological outcome than the matched CCPR group at 3 months post-arrest. In matched ECPR group, younger age, witnessed arrest without initial asystole rhythm, early achievement of mean arterial pressure ≥60 mmHg, low rate of ECPR-related complications, and therapeutic hypothermia were significant factors for expecting good neurologic outcome.

Conclusions

ECPR should be considered as an alternative method for attaining good neurological outcomes in OHCA patients who required prolonged CPR, especially of ≥21 minutes. Younger or witnessed arrest patients without initial asystole were good candidates for ECPR. After implantation of ECPR, early hemodynamic stabilization, prevention of ECPR-related complications, and application of therapeutic hypothermia may improve the neurological outcome.
RRHP: a tag-based approach for 5-hydroxymethylcytosine mapping at single-site resolution
Authors: Petterson Adam , Chung Tzu Hung , Tan Darany , Sun Xueguang , Jia Xi-Yu
Published: September 2014

Current methods for genomic mapping of 5-hydroxymethylcytosine (5hmC) have been limited by either costly sequencing depth, high DNA input, or lack of single-base resolution. We present an approach called Reduced Representation 5-Hydroxymethylcytosine Profiling (RRHP) to map 5hmC sites at single-base resolution by exploiting the use of beta-glucosyltransferase to inhibit enzymatic digestion at the junction where adapters are ligated to a genomic library. Therefore, only library fragments presenting glucosylated 5hmC residues at the junction are sequenced. RRHP can detect sites with low 5hmC abundance, and when combined with RRBS data, 5-methylcytosine and 5-hydroxymethylcytosine can be compared at a specific site.
Big effects of small RNAs on legume root biotic interactions
Authors: Wang Huan , Chua Nam-Hai
Published: September 2014

Comprehensive profiling of microRNAs (miRNAs) from the legume Medicago truncatula reveals the organization of miRNA-based regulatory modules in root biotic interactions.
Abrogation of CC chemokine receptor 9 ameliorates collagen-induced arthritis of mice
Authors: Yokoyama Waka , Kohsaka Hitoshi , Kaneko Kayoko , Walters Matthew , Takayasu Aiko , Fukuda Shin , Miyabe Chie , Miyabe Yoshishige , Love Paul E , Nakamoto Nobuhiro , Kanai Takanori , Watanabe-Imai Kaori , Charvat Trevor T , Penfold Mark ET , Jaen Juan , Schall Thomas J , Harigai Masayoshi , Miyasaka Nobuyuki , Nanki Toshihiro
Published: September 2014

Introduction

Biological drugs are effective in patients with rheumatoid arthritis (RA), but increase severe infections. The CC chemokine receptor (CCR) 9 antagonist was effective for Crohn’s disease without critical adverse effects including infections in clinical trials. The present study was carried out to explore the pathogenic roles of chemokine (C-C motif) ligand (CCL) 25 and its receptor, CCR9, in autoimmune arthritis and to study if the CCR9 antagonist could be a new treatment for RA.

Methods

CCL25 and CCR9 expression was examined with immunohistochemistry and Western blotting. Concentration of interleukin (IL)-6, matrix metalloproteinase (MMP)-3 and tumor necrosis factor (TNF)-α was measured with enzyme-linked immunosorbent assays. Effects of abrogating CCR9 on collagen-induced arthritis (CIA) was evaluated using CCR9-deficient mice or the CCR9 antagonist, CCX8037. Fluorescence labeled-CD11b+ splenocytes from CIA mice were transferred to recipient CIA mice and those infiltrating into the synovial tissues of the recipient mice were counted.

Results

CCL25 and CCR9 proteins were found in the RA synovial tissues. CCR9 was expressed on macrophages, fibroblast-like synoviocytes (FLS) and dendritic cells in the synovial tissues. Stimulation with CCL25 increased IL-6 and MMP-3 production from RA FLS, and IL-6 and TNF-α production from peripheral blood monocytes. CIA was suppressed in CCR9-deficient mice. CCX8037 also inhibited CIA and the migration of transferred CD11b+ splenocytes into the synovial tissues.

Conclusions

The interaction between CCL25 and CCR9 may play important roles in cell infiltration into the RA synovial tissues and inflammatory mediator production. Blocking CCL25 or CCR9 may represent a novel safe therapy for RA.
Clinical subtypes of chronic traumatic encephalopathy: literature review and proposed research diagnostic criteria for traumatic encephalopathy syndrome
Authors: Montenigro Philip H , Baugh Christine M , Daneshvar Daniel H , Mez Jesse , Budson Andrew E , Au Rhoda , Katz Douglas I , Cantu Robert C , Stern Robert A
Published: September 2014

The long-term consequences of repetitive head impacts have been described since the early 20th century. Terms such as punch drunk and dementia pugilistica were first used to describe the clinical syndromes experienced by boxers. A more generic designation, chronic traumatic encephalopathy (CTE), has been employed since the mid-1900s and has been used in recent years to describe a neurodegenerative disease found not just in boxers but in American football players, other contact sport athletes, military veterans, and others with histories of repetitive brain trauma, including concussions and subconcussive trauma. This article reviews the literature of the clinical manifestations of CTE from 202 published cases. The clinical features include impairments in mood (for example, depression and hopelessness), behavior (for example, explosivity and violence), cognition (for example, impaired memory, executive functioning, attention, and dementia), and, less commonly, motor functioning (for example, parkinsonism, ataxia, and dysarthria). We present proposed research criteria for traumatic encephalopathy syndrome (TES) which consist of four variants or subtypes (TES behavioral/mood variant, TES cognitive variant, TES mixed variant, and TES dementia) as well as classifications of ‘probable CTE’ and ‘possible CTE’. These proposed criteria are expected to be modified and updated as new research findings become available. They are not meant to be used for a clinical diagnosis. Rather, they should be viewed as research criteria that can be employed in studies of the underlying causes, risk factors, differential diagnosis, prevention, and treatment of CTE and related disorders.
Full-wavefield inversion of surface waves for mapping embedded low-velocity zones in permafrost
Authors: Dou Shan , Ajo-Franklin Jonathan B.
Published: September 2014

Surface waves are advantageous for mapping seismic structures of permafrost, in which irregular velocity gradients are common and thus the effectiveness of refraction methods are limited. Nevertheless, the complex velocity structures that are common in permafrost environments often yield unusual dispersion spectra, in which higher-order and leaky modes are dominant. Such unusual dispersion spectra were prevalent in the multichannel surface-wave data acquired from our permafrost study site at Barrow, Alaska. Owing to the difficulties in picking and identifying dispersion curves from these dispersion spectra, conventional surface-wave inversion methods become problematic to apply. To overcome these difficulties, we adopted a full-wavefield method to invert for velocity models that can best fit the dispersion spectra instead of the dispersion curves. The inferred velocity models were consistent with collocated electric resistivity results and with subsequent confirmation cores, which indicated the reliability of the recovered seismic structures. The results revealed embedded low-velocity zones underlying the ice-rich permafrost at our study site — an unexpected feature considering the low ground temperatures of [Formula: see text] to [Formula: see text]. The low velocities in these zones ([Formula: see text] lower than the overlying ice-rich permafrost) were most likely caused by saline pore-waters that prevent the ground from freezing, and the resultant velocity structures are vivid examples of complex subsurface properties in permafrost terrain. We determined that full-wavefield inversion of surface waves, although carrying higher computational costs than conventional methods, can be an effective tool for delineating the seismic structures of permafrost.
Tamibarotene As Maintenance Therapy for Acute Promyelocytic Leukemia: Results From a Randomized Controlled Trial
Authors: Shinagawa Katsuji , Yanada Masamitsu , Sakura Toru , Ueda Yasunori , Sawa Masashi , Miyatake Junichi , Dobashi Nobuaki , Kojima Minoru , Hatta Yoshihiro , Emi Nobuhiko , Tamaki Shigehisa , Gomyo Hiroshi , Yamazaki Etsuko , Fujimaki Katsumichi , Asou Norio , Matsuo Keitaro , Ohtake Shigeki , Miyazaki Yasushi , Ohnishi Kazunori , Kobayashi Yukio , Naoe Tomoki
Published: September 2014

Purpose

The introduction of all-trans-retinoic acid (ATRA) has significantly improved outcomes for acute promyelocytic leukemia (APL), although a subset of patients still suffer relapse. The purpose of this study was to evaluate the role of maintenance therapy with the synthetic retinoid tamibarotene in APL.

Patients and Methods

Patients with newly diagnosed APL in molecular remission at the end of consolidation therapy were randomly assigned to receive ATRA or tamibarotene, both orally, for 14 days every 3 months for up to 2 years.

Results

A total of 347 patients were enrolled. Of the 344 eligible patients, 319 (93%) achieved complete remission. After completing three courses of consolidation therapy, 269 patients underwent maintenance random assignment. The relapse-free survival (RFS) rate at 4 years was 84% for the ATRA arm and 91% for the tamibarotene arm (hazard ratio [HR], 0.54; 95% CI, 0.26 to 1.13). When the analysis was restricted to 52 high-risk patients with an initial WBC count ≥ 10.0 × 109/L, the intergroup difference was statistically significant, with 4-year RFS rates of 58% for the ATRA arm and 87% for the tamibarotene arm (HR, 0.26; 95% CI, 0.07 to 0.95). For patients with non–high-risk disease, the HR was 0.82 (95% CI, 0.32 to 2.01). The test for interaction between treatment effects and these subgroups resulted in P = .075. Both treatments were generally well tolerated.

Conclusion

In this trial, no difference was detected between ATRA and tamibarotene for maintenance therapy. In an exploratory analysis, there was a suggestion of improved efficacy of tamibarotene in high-risk patients, but this requires further study.
Kiss1 Neurons Drastically Change Their Firing Activity in Accordance With the Reproductive State: Insights From a Seasonal Breeder
Authors: Hasebe Masaharu , Kanda Shinji , Shimada Hiroyuki , Akazome Yasuhisa , Abe Hideki , Oka Yoshitaka
Published: September 2014

Kisspeptin (Kiss) neurons show drastic changes in kisspeptin expression in response to the serum sex steroid concentration in various vertebrate species. Thus, according to the reproductive states, kisspeptin neurons are suggested to modulate various neuronal activities, including the regulation of GnRH neurons in mammals. However, despite their reproductive state-dependent regulation, there is no physiological analysis of kisspeptin neurons in seasonal breeders. Here we generated the first kiss1-enhanced green fluorescent protein transgenic line of a seasonal breeder, medaka, for histological and electrophysiological analyses using a whole-brain in vitro preparation in which most synaptic connections are intact. We found histologically that Kiss1 neurons in the nucleus ventralis tuberis (NVT) projected to the preoptic area, hypothalamus, pituitary, and ventral telencephalon. Therefore, NVT Kiss1 neurons may regulate various homeostatic functions and innate behaviors. Electrophysiological analyses revealed that they show various firing patterns, including bursting. Furthermore, we found that their firings are regulated by the resting membrane potential. However, bursting was not induced from the other firing patterns with a current injection, suggesting that it requires some chronic modulations of intrinsic properties such as channel expression. Finally, we found that NVT Kiss1 neurons drastically change their neuronal activities according to the reproductive state and the estradiol levels. Taken together with the previous reports, we here conclude that the breeding condition drastically alters the Kiss1 neuron activities in both gene expression and firing activities, the latter of which is strongly related to Kiss1 release, and the Kiss1 peptides regulate the activities of various neural circuits through their axonal projections.
Twin-Spirited Woman
Authors: Wesley Saylesh
Published: September 2014

Coast Salish people, particularly the Stó:lõ of the lower Fraser Valley, have lost much of their language, histories, and teachings as a result of colonization. One such important identity that has been forgotten or erased is the two-spirited role. The author wishes to revitalize the cultural roles of transgendered/two-spirit people within the Coast Salish territory and ways in which they historically contributed to their societies prior to colonization. Traditionally, the Stó:lõ are matriarchal and matrilineal, and only grandmothers can create any new laws for their descendants. Thus given the vital role played by the author's grandmother in her process, this essay is a long-overdue proposal to all living grandmothers not only to stand by and accept their two-spirited grandchildren but to call for a celebration of their coming out. This visionary work serves to inspire future generations of Stó:lõ to fully embrace all members of their community, especially two-spirits. The first Sts'iyóye Smestíyexw Slhá:li, or Twin-Spirited Woman, as this essay is about, offers an example to this sacred work.
For a Queer Pedagogy of Friendship
Authors: Cornejo Giancarlo
Published: September 2014

This hybrid essay/narrative attempts to give an account of the survival of a “queer” subject, specifically a trans child living in Lima, Peru, in the 1950s and 1960s. My theoretical claims may be simple, but the survival of this trans child was anything but simple. The essay argues that in the survival of this child, friendship played a vital role.
Toms and Zees
Authors: Ravine Jai Arun
Published: September 2014

Who is Zee? Zee is a site of dissonance that helps illustrate how Thai and Western concepts of gender and queerness converge and collide. How Zee is frequently recognized as male but then constantly reiterated as female while embodying a certain gender ambiguity in language and appearance is a product of the slippage between geographically and culturally specific understandings of gender, which unfortunately causes Thai FTMs in both the United States and Thailand to experience isolation and alienation from Thai community, a silence camouflaged by that very ambiguity.
Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord
Authors: Vue Tou Yia , Kim Euiseok J. , Parras Carlos M. , Guillemot Francois , Johnson Jane E.
Published: September 2014

Glia constitute the majority of cells in the mammalian central nervous system and are crucial for neurological function. However, there is an incomplete understanding of the molecular control of glial cell development. We find that the transcription factor Ascl1 (Mash1), which is best known for its role in neurogenesis, also functions in both astrocyte and oligodendrocyte lineages arising in the mouse spinal cord at late embryonic stages. Clonal fate mapping in vivo reveals heterogeneity in Ascl1-expressing glial progenitors and shows that Ascl1 defines cells that are restricted to either gray matter (GM) or white matter (WM) as astrocytes or oligodendrocytes. Conditional deletion of Ascl1 post-neurogenesis shows that Ascl1 is required during oligodendrogenesis for generating the correct numbers of WM but not GM oligodendrocyte precursor cells, whereas during astrocytogenesis Ascl1 functions in balancing the number of dorsal GM protoplasmic astrocytes with dorsal WM fibrous astrocytes. Thus, in addition to its function in neurogenesis, Ascl1 marks glial progenitors and controls the number and distribution of astrocytes and oligodendrocytes in the GM and WM of the spinal cord.
Efficient homologous recombination-mediated genome engineering in zebrafish using TALE nucleases
Authors: Shin Jimann , Chen Jiakun , Solnica-Krezel Lilianna
Published: September 2014

Custom-designed nucleases afford a powerful reverse genetic tool for direct gene disruption and genome modification in vivo. Among various applications of the nucleases, homologous recombination (HR)-mediated genome editing is particularly useful for inserting heterologous DNA fragments, such as GFP, into a specific genomic locus in a sequence-specific fashion. However, precise HR-mediated genome editing is still technically challenging in zebrafish. Here, we establish a GFP reporter system for measuring the frequency of HR events in live zebrafish embryos. By co-injecting a TALE nuclease and GFP reporter targeting constructs with homology arms of different size, we defined the length of homology arms that increases the recombination efficiency. In addition, we found that the configuration of the targeting construct can be a crucial parameter in determining the efficiency of HR-mediated genome engineering. Implementing these modifications improved the efficiency of zebrafish knock-in generation, with over 10% of the injected F0 animals transmitting gene-targeting events through their germline. We generated two HR-mediated insertion alleles of sox2 and gfap loci that express either superfolder GFP (sfGFP) or tandem dimeric Tomato (tdTomato) in a spatiotemporal pattern that mirrors the endogenous loci. This efficient strategy provides new opportunities not only to monitor expression of endogenous genes and proteins and follow specific cell types in vivo, but it also paves the way for other sophisticated genetic manipulations of the zebrafish genome.
Systematic profiling of spatiotemporal tissue and cellular stiffness in the developing brain
Authors: Iwashita Misato , Kataoka Noriyuki , Toida Kazunori , Kosodo Yoichi
Published: September 2014

Accumulating evidence implicates the significance of the physical properties of the niche in influencing the behavior, growth and differentiation of stem cells. Among the physical properties, extracellular stiffness has been shown to have direct effects on fate determination in several cell types in vitro. However, little evidence exists concerning whether shifts in stiffness occur in vivo during tissue development. To address this question, we present a systematic strategy to evaluate the shift in stiffness in a developing tissue using the mouse embryonic cerebral cortex as an experimental model. We combined atomic force microscopy measurements of tissue and cellular stiffness with immunostaining of specific markers of neural differentiation to correlate the value of stiffness with the characteristic features of tissues and cells in the developing brain. We found that the stiffness of the ventricular and subventricular zones increases gradually during development. Furthermore, a peak in tissue stiffness appeared in the intermediate zone at E16.5. The stiffness of the cortical plate showed an initial increase but decreased at E18.5, although the cellular stiffness of neurons monotonically increased in association with the maturation of the microtubule cytoskeleton. These results indicate that tissue stiffness cannot be solely determined by the stiffness of the cells that constitute the tissue. Taken together, our method profiles the stiffness of living tissue and cells with defined characteristics and can therefore be utilized to further understand the role of stiffness as a physical factor that determines cell fate during the formation of the cerebral cortex and other tissues.
Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse
Authors: Chojnowski Jena L. , Masuda Kyoko , Trau Heidi A. , Thomas Kirk , Capecchi Mario , Manley Nancy R.
Published: September 2014

Hoxa3 was the first Hox gene to be mutated by gene targeting in mice and is required for the development of multiple endoderm and neural crest cell (NCC)-derived structures in the pharyngeal region. Previous studies have shown that the Hoxa3 null mutant lacks third pharyngeal pouch derivatives, the thymus and parathyroids by E18.5, and organ-specific markers are absent or downregulated during initial organogenesis. Our current analysis of the Hoxa3 null mutant shows that organ-specific domains did undergo initial patterning, but the location and timing of key regional markers within the pouch, including Tbx1, Bmp4 and Fgf8, were altered. Expression of the parathyroid marker Gcm2 was initiated but was quickly downregulated and differentiation failed; by contrast, thymus markers were delayed but achieved normal levels, concurrent with complete loss through apoptosis. To determine the cell type-specific roles of Hoxa3 in third pharyngeal pouch development, we analyzed tissue-specific mutants using endoderm and/or NCC-specific Cre drivers. Simultaneous deletion with both drivers resulted in athymia at E18.5, similar to the null. By contrast, the individual tissue-specific Hoxa3 deletions resulted in small, ectopic thymi, although each had a unique phenotype. Hoxa3 was primarily required in NCCs for morphogenesis. In endoderm, Hoxa3 temporally regulated initiation of the thymus program and was required in a cell-autonomous manner for parathyroid differentiation. Furthermore, Hoxa3 was required for survival of third pharyngeal pouch-derived organs, but expression in either tissue was sufficient for this function. These data show that Hoxa3 has multiple complex and tissue-specific functions during patterning, differentiation and morphogenesis of the thymus and parathyroids.
The birth of quail chicks after intracytoplasmic sperm injection
Authors: Mizushima Shusei , Hiyama Gen , Shiba Kogiku , Inaba Kazuo , Dohra Hideo , Ono Tamao , Shimada Kiyoshi , Sasanami Tomohiro
Published: September 2014

Intracytoplasmic sperm injection (ICSI) has been successfully used to produce offspring in several mammalian species including humans. However, ICSI has not been successful in birds because of the size of the egg and difficulty in mimicking the physiological polyspermy that takes place during normal fertilization. Microsurgical injection of 20 or more spermatozoa into an egg is detrimental to its survival. Here, we report that injection of a single spermatozoon with a small volume of sperm extract (SE) or its components led to the development and birth of healthy quail chicks. SE contains three factors – phospholipase Cζ (PLCZ), aconitate hydratase (AH) and citrate synthase (CS) – all of which are essential for full egg activation and subsequent embryonic development. PLCZ induces an immediate, transient Ca2+ rise required for the resumption of meiosis. AH and CS are required for long-lasting, spiral-like Ca2+ oscillations within the activated egg, which are essential for cell cycle progression in early embryos. We also found that co-injection of cRNAs encoding PLCZ, AH and CS support the full development of ICSI-generated zygotes without the use of SE. These findings will aid our understanding of the mechanism of avian fertilization and embryo development, as well as assisting in the manipulation of the avian genome and the production of transgenic and cloned birds.
Molybdenum Source for Increase of Molybdenum Content in Electrodeposited Cu–Mo Composites
Authors: Gotou Miku , Arakawa Tomiyuki , Watanabe Nobuaki , Hara Takatoshi , Tomita Tatsuya , Hashimoto Akira , Takanashi Hiroshi , Koiwa Ichiro
Published: September 2014

Cu–Mo composites have been expected to be materials of heat sinks in electron devices. We have formed Cu–Mo composites by electrodeposition. Molybdenum content in Cu–Mo composites formed by using Na2MoO4 was larger than that in ones formed by using H3(PMo12O40). Molybdenum content, over 30 wt % in Cu–Mo composites was obtained.
Functional analysis of Kaposi's sarcoma–associated herpesvirus vFLIP expression reveals a new mode of IRES-mediated translation
Authors: Othman Zulkefley , Sulaiman Mariam K. , Willcocks Margaret M. , Ulryck Nathalie , Blackbourn David J. , Sargueil Bruno , Roberts Lisa O. , Locker Nicolas
Published: September 2014

Kaposi's sarcoma–associated herpesvirus (KSHV) is an oncogenic virus, the etiological agent of Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). One of the key viral proteins that contributes to tumorigenesis is vFLIP, a viral homolog of the FLICE inhibitory protein. This KSHV protein interacts with the NFκB pathway to trigger the expression of antiapoptotic and proinflammatory genes and ultimately leads to tumor formation. The expression of vFLIP is regulated at the translational level by an internal ribosomal entry site (IRES) element. However, the precise mechanism by which ribosomes are recruited internally and the exact location of the IRES has remained elusive. Here we show that a 252-nt fragment directly upstream of vFLIP, within a coding region, directs translation. We have established its RNA structure and demonstrate that IRES activity requires the presence of eIF4A and an intact eIF4G. Furthermore, and unusually for an IRES, eIF4E is part of the complex assembled onto the vFLIP IRES to direct translation. These molecular interactions define a new paradigm for IRES-mediated translation.
Diverse self-association properties within a family of phage packaging RNAs
Authors: Hao Yumeng , Kieft Jeffrey S.
Published: September 2014

The packaging RNA (pRNA) found in phi29 bacteriophage is an essential component of a molecular motor that packages the phage's DNA genome. The pRNA forms higher-order multimers by intermolecular “kissing” interactions between identical molecules. The phi29 pRNA is a proven building block for nanotechnology and a model to explore the rare phenomenon of naturally occurring RNA self-association. Although the self-association properties of the phi29 pRNA have been extensively studied and this pRNA is used in nanotechnology, the characteristics of phylogenetically related pRNAs with divergent sequences are comparatively underexplored. These diverse pRNAs may lend new insight into both the rules governing RNA self-association and for RNA engineering. Therefore, we used a combination of biochemical and biophysical methods to resolve ambiguities in the proposed secondary structures of pRNAs from M2, GA1, SF5, and B103 phage, and to discover that different naturally occurring pRNAs form multimers of different stoichiometry and thermostability. Indeed, the M2 pRNA formed multimers that were particularly thermostable and may be more useful than phi29 pRNA for many applications. To determine if diverse pRNA behaviors are conferred by different kissing loop sequences, we designed and tested chimeric RNAs based on our revised secondary structural models. We found that although the kissing loops are essential for self-association, the critical determinant of multimer stability and stoichiometry is likely the diverse three-way junctions found in these RNAs. Using known features of RNA three-way junctions and solved structures of phi29 pRNA's junction, we propose a model for how different junctions affect self-association.
Ligand binding by the tandem glycine riboswitch depends on aptamer dimerization but not double ligand occupancy
Authors: Ruff Karen M. , Strobel Scott A.
Published: September 2014

The glycine riboswitch predominantly exists as a tandem structure, with two adjacent, homologous ligand-binding domains (aptamers), followed by a single expression platform. The recent identification of a leader helix, the inclusion of which eliminates cooperativity between the aptamers, has reopened the debate over the purpose of the tandem structure of the glycine riboswitch. An equilibrium dialysis-based assay was combined with binding-site mutations to monitor glycine binding in each ligand-binding site independently to understand the role of each aptamer in glycine binding and riboswitch tertiary interactions. A series of mutations disrupting the dimer interface was used to probe how dimerization impacts ligand binding by the tandem glycine riboswitch. While the wild-type tandem riboswitch binds two glycine equivalents, one for each aptamer, both individual aptamers are capable of binding glycine when the other aptamer is unoccupied. Intriguingly, glycine binding by aptamer-1 is more sensitive to dimerization than glycine binding by aptamer-2 in the context of the tandem riboswitch. However, monomeric aptamer-2 shows dramatically weakened glycine-binding affinity. In addition, dimerization of the two aptamers in trans is dependent on glycine binding in at least one aptamer. We propose a revised model for tandem riboswitch function that is consistent with these results, wherein ligand binding in aptamer-1 is linked to aptamer dimerization and stabilizes the P1 stem of aptamer-2, which controls the expression platform.
Digital Content Provision and Optimal Copyright Protection
Authors: Guo Liang , Meng Xiangyi
Published: September 2014

Advances in digital technologies have led to an increasing concern about piracy for providers of digital content (e.g., e-books, games, music, software, videos). Yet controversies exist over the influence of copyright protection on firm profitability. The objective of this paper is to provide an alternative rationale for the growing anti-protection trend and to investigate optimal copyright enforcement and quality provision in a monopoly setting. The proposed economic mechanism centers on the influence of copyright protection on consumer search when consumers can get to know the firm’s actions (e.g., price, quality) only after costly search. We show that more stringent copyright protection can induce the consumers to rationally expect lower ex post surplus, thus exerting a negative strategic effect on the consumers' willingness to search. This strategic effect may outweigh the positive main effect on the relative attractiveness of the authorized versus the pirated product, which can hence explain the optimality of incomplete and even zero copyright protection policies in markets where consumer prepurchase search is important (e.g., information goods, digital products). It is also because of this strategic effect that the firm may provide lower quality as copyright enforcement increases. Interestingly, quality unobservability can moderate this strategic effect and thus lead to an increasing incentive for copyright protection.

This paper was accepted by Pradeep Chintagunta, marketing.
Tongue problems, in images
Authors: Watkins Jean
Published: September 2014

The human tongue is prone to various types of infection. Jean Watkins describes the causes, symptoms and treatment for some of the most common presentations.
Clinical outcomes and quality of life for home haemodialysis patients
Authors: Mitra Sandip , Jayanti Anuradha
Published: September 2014

Despite the many benefits associated with home haemodialysis, in-centre dialysis is considered the mainstay of treatment for renal disease. Sandip Mitra and Anuradha Jayanti explore the revival of home haemodialysis in the UK and recommend areas for the future study of this modality based on clinical outcomes, technique failure, quality of life measures and cost-effectiveness.
Management of new-onset diabetes post transplantation: calcineurin inhibitors and corticosteroids
Authors: Coleman Adrian , Chai Mee Onn
Published: September 2014

New-onset diabetes after transplantation (NODAT) is a serious and common post-transplant complication. Mee Onn Chai and Adrian Coleman discuss how tacrolimus and prednisolone are associated with the development of NODAT and outline evidence-based management strategies.
New educational resources for kidney patients
Authors: Lumsdon Angela
Published: September 2014

As well as investing in research, Kidney Research UK develops and distributes resources aimed at supporting and educating patients with chronic kidney disease. Angela Lumsdon provides an overview of two such resources which are helping patients approaching renal failure and their families to understand and make important decisions about dialysis.
Study offers hope in reducing risk of kidney transplant rejection
Authors: Biela Chris
Published: September 2014

Donor rejection is one of the biggest challenges that kidney transplant patients have to face. However, a study published by Oxford University researchers suggests that treatment with a combination of alemtuzumab and tacrolimus could halve the risk of post-transplant rejection.
How to get them talking
Authors: Brodie Kathy , Graham Emma , Good Toni
Published: September 2014

Have you heard of ‘items of provocation’? These are every day objects which can be used to encourage quiet children to begin talking. Kathy Brodie provides tips on how to use them.
Autumn adds up to fun
Authors: Clarke Jenni
Published: September 2014

Start planning ahead for the month of November, and the maths activities that will provide you with opportunities to observe and record how children are progressing. By Jenni Clarke.
Playing the natural way
Authors: Richardson Gail Ryder
Published: September 2014

In the first of a two-part series, Gail Ryder Richardson explores the importance of natural materials and play experiences in relation to children's development, learning, health and wellbeing.
Reach for the stars!
Authors: Chapman Ailsa
Published: September 2014

Making it as a star pupil is an exciting journey which children will engage with, says Ailsa Chapman.
Come into my woodland den
Authors: Williams Brenda
Published: September 2014

The poem Whispering in the Woodland evokes the magical feelings of autumnal changes and animal preparations for winter. Use it help children learn about animal habitats and exciting seasonal changes.
Everyday numbers
Authors: Hampshire Viv
Published: September 2014

Numbers are all around us and becoming familiar with their appearance in everyday environments is essential. The following activities help children explore some of the practical applications of numbers.
Roaring for freedom
Authors: Chalmers Debbie
Published: September 2014

Practitioners can explore a variety of stimulating activities to encourage and develop children's literacy, communication and creative skills, inspired by Peter Brown's picture book.
Breaking the ice
Authors: Hart Karen
Published: September 2014

Water is accessible and versatile and makes a great topic for investigation. The following fun experiments will help you explore some of the properties of water with children.
Wonderful woodwork
Authors: Sharpe Dee
Published: September 2014

Working with wood can give children the sense of creating something durable, and can help foster physical development and creativity. Dee Sharpe provides some ideas to help you explore this material.