bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone deacetylase inhibitor regulates the balance of Th17/Treg in allergic asthma
Authors: Hou Xiaoxia , Wan Huanying , Ai Xiangyan , Shi Yuheng , Ni Yingmeng , Tang Wei , Shi Guochao
Published: October 2014

Background and Aims

The aim of this study is to investigate the expression pattern of histone deacetylase 9 in peripheral blood of patients with allergic asthma and its regulatory effect on the balance of Th17/Treg cells involved in the pathogenesis of asthma.

Methods

flap‐Ub promoter‐GFP‐WRE vector was used to construct the Jurkat‐HA‐FOXP3 cell line. After histone deacetylase inhibitor‐trichostatin A (TSA) treatment, FOXP3 and RORγt expression were detected by real‐time‐polymerase chain reaction (RT‐PCR). BALB/c mice were randomly assigned to control group, TSA treatment and the asthma group. Serum Immunoglobulin E (IgE) was detected with enzyme‐linked immunosorbent assay (ELISA), airway inflammation in lung tissue evaluated by haematoxylin/eosin staining, bronchoalveolar lavage fluid (BALF) cell number and differential counted, interleukin (IL)‐17A and TGF‐β concentrations in BALF measured with ELISA, and expression of RORγt and FOXP3 messenger RNA (mRNA)measured by RT‐PCR. Forty‐seven patients with asthma were recruited and assigned to intermittent, mild and moderate–severe group. GATA3, IL‐4, histone deacetylases (HDAC) 9 mRNA expression level were measured by RT‐PCR.

Results

After TSA treatment, FOXP3 mRNA level was upregulated, while RORγt mRNA level was downregulated. FOXP3 protein level was also upregulated by TSA. In vivo, TSA treatment can inhibit IL‐17 but promote transforming growth factor‐beta production in the BALF of asthma mice, and inhibited the expression of Th17 cells and RORγt mRNA in lung; also can promote Foxp3 mRNA expression. GATA3, IL‐4 mRNA expression levels were upregulated in patients with asthma than the healthy control. HDAC9 mRNA expression level was associated with the severity of disease.

Conclusion

The histone deacetylase inhibitor TSA can regulate the balance of Th17/Treg in asthma by regulating the activity of histone deacetylase.
Beyond climate envelopes: bio‐climate modelling accords with observed 25‐year changes in seabird populations of the British Isles
Authors: Russell Deborah J. F. , Wanless Sarah , Collingham Yvonne C. , Anderson Barbara J. , Beale Colin , Reid James B. , Huntley Brian , Hamer Keith C.
Published: October 2014

Aim

Climate envelope models (CEMs) are used to assess species’ vulnerability to predicted changes in climate, based on their distributions. Extinction risk, however, also depends on demographic parameters. Accordingly, we use CEMs for 18 seabird species to test three hypotheses: (i) population sizes are larger in areas where CEMs fitted using distribution data predict more suitable climate; (ii) the presence of this relationship (Hypothesis i) is related to a species’ foraging ecology; and (iii) species whose distributions and population sizes conformed most closely to indices of climatic suitability in the mid‐1980s experienced the largest population changes following climatic change between 1986 and 2010.

Location

Europe.

Methods

Climate envelope models fitted at a 50‐km resolution using European climatic and distribution data were applied using local climatic data to calculate local climatic suitability indices (CSIs) for 18 species within the British Isles. We then investigated the relationship between CSI and population size at a 10‐km resolution and related both the presence of this relationship and goodness‐of‐fit metrics from the European models to changes in population size (1986–2010).

Results

Local population sizes were significantly positively related to local CSI in 50% of species, providing support for Hypothesis (i), and these 50% of species were independently considered to be most vulnerable to changes in food availability at sea in support of Hypothesis (ii). Those species whose distributions and populations most closely conformed to indices of climatic suitability showed the least favourable subsequent changes in population size, over a period in which mean climatic suitability decreased for all species, in support of Hypothesis (iii).

Main conclusions

Climate influences the population sizes of multiple seabird species in the British Isles. We highlight the potential for outputs of CEMs fitted with coarse resolution occupancy data to provide information on both local abundance and sensitivity to future climate changes.
MARKET STRUCTURE AND MEDIA DIVERSITY
Authors: Hiller R. Scott , Savage Scott J. , Waldman Donald M.
Published: October 2014

We estimate a mixed logit model of the demand for local news service. Results provide evidence that suggest the representative consumer values more diverse news, more coverage of multicultural issues, and more information on community news, and has a distaste for advertising. Demand estimates are used to calculate the impact on consumer welfare from a marginal decrease in the number of independent television stations that lowers the amount of diversity, multiculturalism, community news, and advertising. Consumer welfare decreases, but the losses are smaller in large markets. For example, small‐market consumers lose $45 million annually while large‐market consumers lose $13 million. (JEL C9, C25, L13, L82, L96)
FAST TIMES DURING SPRING BREAKS: ARE TRAFFIC FATALITIES ANOTHER CONSEQUENCE?
Authors: French Michael T. , Gumus Gulcin
Published: October 2014

Every year in the United States, millions of college students travel for spring break, spending billions of dollars. We examine a potential adverse consequence of spring break that has received little attention in the literature—traffic safety. In particular, we estimate the impact of spring break season on fatal passenger vehicle crashes. Using daily county‐level longitudinal data on traffic fatalities in popular spring break destinations from 1982 to 2011, we conduct separate analyses by age groups, license status, and alcohol involvement in the crash. Our findings indicate that passenger vehicle fatalities are significantly overrepresented during the spring break season. (JEL I12, I18, H73)
Beta2 oscillations (23–30 Hz) in the mouse hippocampus during novel object recognition
Authors: França Arthur S. C. , do Nascimento George C. , Lopes‐dos‐Santos Vítor , Muratori Larissa , Ribeiro Sidarta , Lobão‐Soares Bruno , Tort Adriano B. L.
Published: October 2014

The oscillatory activity of hippocampal neuronal networks is believed to play a role in memory acquisition and consolidation. Particular focus has been given to characterising theta (4–12 Hz), gamma (40–100 Hz) and ripple (150–250 Hz) oscillations. Beyond these well‐described network states, few studies have investigated hippocampal beta2 (23–30 Hz) activity in vivo and its link to behaviour. A previous sudy showed that the exploration of novel environments may lead to the appearance of beta2 oscillations in the mouse hippocampus. In the present study we characterised hippocampal beta2 oscillations in mice during an object recognition task. We found prominent bursts of beta2 oscillations in the beginning of novel exploration sessions (four new objects), which could be readily observed by spectral analysis and visual inspection of local field potentials. Beta2 modulated hippocampal but not neocortical neurons and its power decreased along the session. We also found increased beta2 power in the beginning of a second exploration session performed 24 h later in a slightly modified environment (two new, two familiar objects), but to a lesser extent than in the first session. However, the increase in beta2 power in the second exploration session became similar to the first session when we pharmacologically impaired object recognition in a new set of experiments performed 1 week later. Our results suggest that hippocampal beta2 activity is associated with a dynamic network state tuned for novelty detection and which may allow new learning to occur.
Cortical indices of sound localization mature monotonically in early infancy
Authors: Slugocki Christopher , Trainor Laurel J.
Published: October 2014

In human neonates, orienting behavior in response to an off‐midline sound source disappears around the first postnatal month, only to re‐emerge at ~4 months. To date, it is unclear whether sound localization processes continue to operate between postnatal months 1 and 3. Here, we used an event‐related potential, reflecting change detection in the auditory cortices, to measure the cortical responses elicited by large (± 90° relative to midline), infrequent changes in sound source location in 2‐, 5‐, 8‐ and 13‐month‐old infants. Both fast‐negative mismatch negativity (MMN) Näätänen et al. (2007) and slow‐positive mismatch response (MMR) Trainor et al. (2003) were elicited from all age groups. However, both components were smaller and the fast‐negative component occurred later in the 2‐month‐old group than in older age groups. Additionally, the slow‐positive component tended to diminish in amplitude with increasing age, whereas the fast‐negative component grew larger and tended to occur earlier with increasing age. These results suggest that the cortical representation of sound location matures similarly to representations of pitch and duration. A subsequent investigation of 2‐month‐old infants confirmed that the observed MMR and MMN were elicited by changes in sound source location, and were not merely attributable to changes in loudness cues. The presence of both MMR and MMN in the 2‐month‐old group indicates that the cortex is able to detect changes in sound location despite the behavioral insensitivity observed around 1–3 months of age.
Corticosterone and corticotropin‐releasing factor acutely facilitate gamma oscillations in the hippocampus in vitro
Authors: Çalışkan Gürsel , Schulz Steffen B. , Gruber David , Behr Joachim , Heinemann Uwe , Gerevich Zoltan
Published: October 2014

Stressful experiences do not only cause peripheral changes in stress hormone levels, but also affect central structures such as the hippocampus, implicated in spatial orientation, stress evaluation, and learning and memory. It has been suggested that formation of memory traces is dependent on hippocampal gamma oscillations observed during alert behaviour and rapid eye movement sleep. Furthermore, during quiescent behaviour, sharp wave‐ripple (SW‐R) activity emerges. These events provide a temporal window during which reactivation of memory ensembles occur. We hypothesized that stress‐responsive modulators, such as corticosterone (CORT), corticotropin‐releasing factor (CRF) and the neurosteroid 3α, 21‐dihydroxy‐5α‐pregnan‐20‐one (THDOC) are able to modulate gamma oscillations and SW‐Rs. Using in vitro hippocampal slices, we studied acute and subacute (2 h) impact of these agents on gamma oscillations in area cornu ammonis 3 of the ventral hippocampus induced by acetylcholine (10 μm) combined with physostigmine (2 μm). CORT increased the gamma oscillations in a dose‐dependent fashion. This effect was mediated by glucocorticoid receptors. Likewise, CRF augmented gamma oscillations via CRF type 1 receptor. Lastly, THDOC was found to diminish cholinergic gamma oscillations in a dose‐dependent manner. Neither CORT, CRF nor THDOC modulated gamma power when pre‐applied for 1 h, 2 h before the induction of gamma oscillations. Interestingly, stress‐related neuromodulators had rather mild effects on spontaneous SW‐R compared with their effects on gamma oscillations. These data suggest that the alteration of hippocampal gamma oscillation strength in vitro by stress‐related agents is an acute process, permitting fast adaptation to new attention‐requiring situations in vivo.
Stabilizing effects of diversity on aboveground wood production in forest ecosystems: linking patterns and processes
Authors: Jucker Tommaso , Bouriaud Olivier , Avacaritei Daniel , Coomes David A.
Published: October 2014

Both theory and evidence suggest that diversity stabilises productivity in herbaceous plant communities through a combination of overyielding, species asynchrony and favourable species interactions. However, whether these same processes also promote stability in forest ecosystems has never been tested. Using tree ring data from permanent forest plots across Europe, we show that aboveground wood production is inherently more stable through time in mixed‐species forests. Faster rates of wood production (i.e. overyielding), decreased year‐to‐year variation in productivity through asynchronous responses of species to climate, and greater temporal stability in the growth rates of individual tree species all contributed strongly to stabilising productivity in mixed stands. Together, these findings reveal the central role of diversity in stabilising productivity in forests, and bring us closer to understanding the processes which enable diverse forests to remain productive under a wide range of environmental conditions.
Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis
Authors: Sundal C. , Baker M. , Karrenbauer V. , Gustavsen M. , Bedri S. , Glaser A. , Myhr K.‐M. , Haugarvoll K. , Zetterberg H. , Harbo H. , Kockum I. , Hillert J. , Wszolek Z. , Rademakers R. , Andersen O.
Published: October 2014

Background and purpose

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a devastating, hereditary white matter (WM) disorder with heterogeneous neuropsychiatric features. Colony stimulating factor 1 receptor (CSF1R) mutations were looked for in primary progressive multiple sclerosis (PPMS) patients and the clinical features of a family with a novel CSF1R mutation are reported.

Methods

CSF1R exons 12−22 in a cohort of 220 PPMS patients from the Swedish and Norwegian national multiple sclerosis registries were sequenced.

Results

One patient had a novel mutation, c.2562T>A; p.Asn854Lys, in the CSF1R gene. Her symptoms started at the age of 29 years with insidious onset of pyramidal weakness in the left leg. The cerebrospinal fluid examination showed four intrathecal immunoglobulin G bands. A magnetic resonance imaging scan performed 4 years after symptom onset demonstrated patchy deep WM lesions. She was diagnosed as having PPMS and treated with intramuscular interferon beta 1a. Due to slow disease progression, the development of memory decline and cerebellar signs, she was given subcutaneous interferon beta 1a without any benefit. The updated pedigree indicated that five siblings also had the CSF1R gene mutation; one was diagnosed with PPMS. Six more distant relatives also had a neurological disorder; four were clinically diagnosed with PPMS.

Conclusions

Our study indicates that a chronic course of HDLS may mimic PPMS. Genetic testing for CSF1R gene mutations in PPMS cases with a positive family history of neurological disorders may establish the diagnosis of HDLS.
Identification of novel peptides from amphibian (Xenopus tropicalis) skin by direct tissue MALDI‐MS analysis
Authors: Shigeri Yasushi , Yasuda Akikazu , Hagihara Yoshihisa , Nishi Kaito , Watanabe Kunihiko , Imura Tomohiro , Inagaki Hidetoshi , Haramoto Yoshikazu , Ito Yuzuru , Asashima Makoto
Published: October 2014

Twelve novel peptides (Pxt‐1 to Pxt‐12) were isolated from the skin of Xenopus tropicalis, diploid frogs, using topological MS analysis. Among them, Pxt‐8, Pxt‐9, and Pxt‐10 were the N terminus of Pxt‐1, N terminus of Pxt‐3 and C terminus of Pxt‐11, respectively. The Pxt‐3 and Pxt‐11 peptides shared significant sequence homologies with magainins 1, ‐2 and levitide, respectively, which all isolated from X. laevis. Pxt‐12 was identical to the X. tropicalis XT‐6‐like precursor previously isolated by ESI‐MS/MS. None of the Pxt peptides contained any Cys, Asp, Tyr or Trp, although Leu and Lys were frequently found as typical frog‐skin peptides. RT‐PCR analysis confirmed the gene expressions of Pxt‐2, Pxt‐3, Pxt‐4, Pxt‐5, Pxt‐7 and Pxt‐11 in X. tropicalis skin. Several ion peaks corresponding to all identified Pxt peptides were observed with MALDI‐MS analysis of X. tropicalis secretory fluids, collected after in vivo stimulation, which suggested that Pxt peptides were definitely secretory molecules. CD studies and Schiffer–Edmundson helical wheel projections suggested that Pxt‐5, as well as mastoparan, at least, could form a typical amphiphilic α helix without a phospholipid or a membrane‐mimetic solvent (trifluoroethanol). Moreover, Pxt‐2 and Pxt‐5 showed growth inhibitory effects on both Escherichia coli (Gram‐negative) and Staphylococcus aureus (Gram‐positive). Measurements of dynamic light scattering and the surface tensions of Pxt peptides solutions suggested that both Pxt‐2 and Pxt‐5 could form associations as micelles and behave like a general surfactant. Moreover, the remarkable foaming properties of Pxt‐2 and Pxt‐5 were observed, as well as those of the secretory fluids of X. tropicalis.
Uncovering the volatile nature of tropical coastal marine ecosystems in a changing world
Authors: Exton Dan A. , McGenity Terry J. , Steinke Michael , Smith David J. , Suggett David J.
Published: October 2014

Biogenic volatile organic compounds (BVOCs), in particular dimethyl sulphide (DMS) and isoprene, have fundamental ecological, physiological and climatic roles. Our current understanding of these roles is almost exclusively established from terrestrial or oceanic environments but signifies a potentially major, but largely unknown, role forBVOCs in tropical coastal marine ecosystems. The tropical coast is a transition zone between the land and ocean, characterized by highly productive and biodiverse coral reefs, seagrass beds and mangroves, which house primary producers that are amongst the greatest emitters ofBVOCs on the planet. Here, we synthesize our existing understanding ofBVOCemissions to produce a novel conceptual framework of the tropical marine coast as a continuum fromDMS‐dominated reef producers to isoprene‐dominated mangroves. We use existing and previously unpublished data to consider how current environmental conditions shapeBVOCproduction across the tropical coastal continuum, and in turn howBVOCs can regulate environmental stress tolerance or species interactions via infochemical networks. We use this as a framework to discuss how existing predictions of future tropical coastalBVOCemissions, and the roles they play, are effectively restricted to present day ‘baseline’ trends ofBVOCproduction across species and environmental conditions; as such, there remains a critical need to focus research efforts onBVOCresponses to rapidly accelerating anthropogenic impacts at local and regional scales. We highlight the complete lack of current knowledge required to understand the future ecological functioning of these important systems, and to predict whether feedback mechanisms are likely to regulate or exacerbate current climate change scenarios through environmentally and ecologically mediated changes toBVOCbudgets at the ecosystem level.
An analytical solution for solitary porosity waves: dynamic permeability and fluidization of nonlinear viscous and viscoplastic rock
Authors: Connolly J. A. D. , Podladchikov Y. Y.
Published: October 2014

Porosity waves are a mechanism by which fluid generated by devolatilization and melting, or trapped during sedimentation, may be expelled from ductile rocks. The waves correspond to a steady‐state solution to the coupled hydraulic and rheologic equations that govern flow of the fluid through the matrix and matrix deformation. This work presents an intuitive analytical formulation of this solution in one dimension that is general with respect to the constitutive relations used to define the viscous matrix rheology and permeability. This generality allows for the effects of nonlinear viscous matrix rheology and disaggregation. The solution combines the porosity dependence of the rheology and permeability in a single hydromechanical potential as a function of material properties and wave velocity. With the ansatz that there is a local balance between fluid production and transport, the solution permits prediction of the dynamic variations in permeability and pressure necessary to accommodate fluid production. The solution is used to construct a phase diagram that defines the conditions for smooth pervasive flow, wave‐propagated flow, and matrix fluidization (disaggregation). The viscous porosity wave mechanism requires negative effective pressure to open the porosity in the leading half of a wave. In nature, negative effective pressure may induce hydrofracture, resulting in a viscoplastic compaction rheology. The tubelike porosity waves that form in such a rheology channelize fluid expulsion and are predicted by geometric argumentation from the one‐dimensional viscous solitary wave solution.
Experimental design for stable genetic manipulation in mammalian cell lines: lentivirus and alternatives
Authors: Shearer Robert F. , Saunders Darren N.
Published: October 2014

The use of third‐generation lentiviral vectors is now commonplace in most areas of basic biology. These systems provide a fast, efficient means for modulating gene expression, but experimental design needs to be carefully considered to minimize potential artefacts arising from off‐target effects and other confounding factors. This review offers a starting point for those new to lentiviral‐based vector systems, addressing the main issues involved with the use of lentiviral systems in vitro and outlines considerations which should be taken into account during experimental design. Factors such as selecting an appropriate system and controls, and practical titration of viral transduction are important considerations for experimental design. We also briefly describe some of the more recent advances in genome editing technology. TALENs and CRISPRs offer an alternative to lentivirus, providing endogenous gene editing with reduced off‐target effects often at the expense of efficiency.
Transcription cofactor PC4 plays essential roles in collaboration with the small subunit of general transcription factor TFIIE
Authors: Akimoto Yusuke , Yamamoto Seiji , Iida Satoshi , Hirose Yutaka , Tanaka Aki , Hanaoka Fumio , Ohkuma Yoshiaki
Published: October 2014

In eukaryotes, positive cofactor 4 (PC4) stimulates activator‐dependent transcription by facilitating transcription initiation and the transition from initiation to elongation. It also forms homodimers and binds to single‐stranded DNA and various transcriptional activators, including the general transcription factor TFIIH. In this study, we further investigated PC4 from Homo sapiens and the nematode Caenorhabditis elegans (hPC4 and cePC4, respectively). hPC4 strongly stimulated transcription on a linearized template, whereas it alleviated transcription on a supercoiled template. Transcriptional stimulation by PC4 was also alleviated by increasing the amount of TFIID. GST pull‐down studies with general transcription factors indicated that both hPC4 and cePC4 bind strongly to TFIIB, TFIIEβ, TFIIFα, TFIIFβ and TFIIH XPB subunits and weakly to TBP and TFIIH p62. However, only hPC4 bound to CDK7. The effect of each PC4 on transcription was studied in combination with TFIIEβ. hPC4 stimulated both basal and activated transcription, whereas cePC4 primarily stimulated activated transcription, especially in the presence of TFIIEβ from C. elegans. Finally, hPC4 bound to the C‐terminal region of hTFIIEβ adjacent to the basic region. These results indicate that PC4 plays essential roles in the transition step from transcription initiation to elongation by binding to melted DNA in collaboration with TFIIEβ.
Greek fathers' experiences from their wife's/partner's labour and delivery: A qualitative approach
Authors: Sapountzi‐Krepia Despina , Psychogiou Maria , Sakellari Evanthia , Tsiligiri Maria , Vehvilainen‐Julkunen Katri
Published: October 2014

This study aimed at exploring Greek fathers' experiences from their wives/partners' labour and delivery, and their perceptions about aspects of delivery care that need to be improved. It took place at hospital maternity clinics at the greater area of Thessaloniki, Greece. Participants were fathers whose wife/partner had given birth one week to one year before the data collection. The data were collected with the use of the Kuopio Instrument for Fathers (KIF). In this article we present the data obtained by KIF's four open‐ended questions, which were analyzed using the method of content analysis.

Three core categories emerged: (i) Meaning of presence during the delivery process; (ii) Experiences of the delivery process; and (iii) Suggestions for improving delivery services.

Fathers take their role seriously and seek an active participation. Healthcare professionals and health education interventions should take into account the fathers' perspectives and aim to meet their needs.
Fever presentation and associated factors in patients with healthcare‐associated bacteraemia
Authors: Lu Shu‐Hua , Yu Po‐Jui , Dai Yu‐Tzu
Published: October 2014

Bacteraemia is a systemic infection associated with strong febrile immune reactions. Fever definitions, fever intensity and other factors might affect the recognition, management and prognosis of patients with bacteraemia. A prospective observational design was used to study 412 consecutive Taiwanese patients with healthcare‐associated bacteraemia. The study variables were fever intensity, factors related to fever intensity, the association of physical function to thermogenic capacity and the sensitivity of three definitions of fever for identifying patients with bacteraemia. Age, Charlson comorbidity index (CCI) score, chills and pathogen types were predictors of fever intensity. Barthel index score, CCI score and pathogen types were predictors of chills, an indicator of thermogenic capacity. The sensitivity of three fever definitions (basal body temperature plus 1°C, ≥ 38°C and ≥ 38.3°C) to identify patients with bacteraemia was 93.3%, 83.5% and 71.4%, respectively. Clinicians can target patients with factors associated with blunted febrile response to bacteraemia for closer monitoring.
Case study of the London 2012 Olympic and Paralympic pharmacy service preparations
Authors: File Hayley , Thomas Trudy , Anderson Geoff
Published: October 2014

Objectives

The Pharmacy Clinical Services Group (PCSG) was formed in 2009. Its aim was to design and deliver a world-class pharmacy service to 250 000 accredited persons and consider the pharmaceutical needs of 9.2 million visitors to the London 2012 Games.

Methods

The explanatory case study method was used to investigate how the PCSG prepared and how they considered the wider vision of the Games. The study investigated two propositions: (1) that the PCSG has a communication function and (2) that it has a design function. A range of data were examined using NVivo 9 data management software.

Key findings

The study identified four emerging themes and a number of subthemes.

Conclusions

The study validated the propositions and highlighted that the PCSG had a leading role within the wider multidisciplinary team. The study found that the PCSG embraced the wider vision of the Games and was exceptionally well prepared to deliver a world-class pharmacy service, anticipating a new gold standard for the provision of pharmacy services for future sporting events.
α1‐Antitrypsin modifies general natural killer cell interactions with dendritic cells and specific interactions with islet β‐cells in favour of protection from autoimmune diabetes
Authors: Guttman Ofer , Yossef Rami , Freixo‐Lima Gabriella , Rider Peleg , Porgador Angel , Lewis Eli C.
Published: October 2014

The autoimmune destruction of pancreatic β‐cells is the hallmark of type 1 diabetes (T1D). Failure of anti‐CD3 antibodies to provide long‐lasting reversal of T1D and the expression of a natural killer (NK) cell ligand on β‐cells suggest that NK cells play a role in disease pathogenesis. Indeed, killing of β‐cells by NK cells has been shown to occur, mediated by activation of the NK cell activating receptor, NKp46. α1‐Antitrypsin (AAT), an anti‐inflammatory and immunomodulatory glycoprotein, protects β‐cells from injurious immune responses and is currently evaluated as a therapeutic for recent onset T1D. Although isolated T lymphocytes are not inhibited by AAT, dendritic cells (DC) become tolerogenic in its presence and other innate immune cells become less inflammatory. Yet a comprehensive profile of NK cell responses in the presence of AAT has yet to be described. In the present study, we demonstrate that AAT significantly reduces NK cell degranulation against β‐cells, albeit in the whole animal and not in isolated NK cell cultures. AAT‐treated mice, and not isolated cultured β‐cells, exhibited a marked reduction in NKp46 ligand levels on β‐cells. In related experiments, AAT‐treated DC exhibited reduced inducible DC‐expressed interleukin‐15 levels and evoked a weaker NK cell response. NK cell depletion in a T1D mouse model resulted in improved β‐cell function and survival, similar to the effects observed by AAT treatment alone; nonetheless, the two approaches were non‐synergistic. Our data suggest that AAT is a selective immunomodulator that retains pivotal NK cell responses, while diverting their activities away from islet β‐cells.
Thermal Depolarization in the High‐Temperature Ternary Piezoelectric System xPbTiO3–yBiScO3–zBi(Ni1/2Ti1/2)O3
Authors: Ansell Troy Y. , Cann David P. , Sapper Eva , Rödel Jürgen
Published: October 2014

In the high‐temperature ternary perovskite piezoelectric system xPbTiO3–yBiScO3–zBi(Ni1/2,Ti1/2)O3 (PT–BS–BNiT), the addition of bismuth to the A site and nickel to the B site leads to compositions that exhibit diffuse relaxor‐like behavior. For these, depolarization temperature, not Curie point, is the critical value of temperature. Depolarization temperature (Td) is defined as the temperature at which the steepest loss in polarization occurs. This temperature is observed in poled materials through two different methods: loss tangent measurements and in situ d33. Across the ternary system, multiple dielectric anomalies occurred which was observed in dielectric tests where the dielectric peak broadens and becomes frequency dependent as BNiT content increased. For different compositions, the value of Td ranged between 275°C–375°C. Values for the piezoelectric coefficient increased with temperature up to d33 = 1000 pC/N during in situ d33. High temperature (up to 190°C) and high field (up to 40 kV/cm) were also applied to test ferroelectric properties in these regimes.
Oxidation Behavior of ZrB2–SiC Composites at Low Pressures
Authors: Tu Rong , Sun Qingyun , Zhang Song , Han Mingxu , Li Qizhong , Hirayama Hidenori , Zhang Lianmeng , Goto Takashi
Published: October 2014

ZrB2‐60 mol%SiC composite with a eutectic microstructure was oxidized at 1573 to 1873 K with reduced total pressures (Ptot) and low oxygen partial pressures (). The mass change was continuously measured by a thermobalance, and then fit with a multiple paralinear model. Oxidation scale of SiO2/ZrO2+SiO2/ZrO2/ZrB2 was formed at  > 0.13 kPa, whereas only porous ZrO2 remained at  < 0.13 kPa, Ptot < 1.33 kPa and higher than 1773 K. With increasing , the parabolic oxidation constant decreased, whereas the linear oxidation constant increased.
A test of the design of a video tutorial for software training
Authors: van der Meij J. , van der Meij H.
Published: October 2014

The effectiveness of a video tutorial versus a paper‐based tutorial for software training has yet to be established. Mixed outcomes from the empirical studies to date suggest that for a video tutorial to outperform its paper‐based counterpart, the former should be crafted so that it addresses the strengths of both designs. This was attempted in the present study. Two consecutive experiments were conducted to examine the effect of tutorial type (video vs. paper based) on task relevance, self‐efficacy, mood, flow and task performance. Participants were students from junior high school. Both studies reported significant, positive contributions of the tutorials to task relevance, self‐efficacy, mood and flow. Both studies also found significant and substantial effects on task performance. A learning gain of about 30% was achieved in both studies. A retention task, completed only in Study 2, further revealed that the learning effect was stable. More importantly, performance on this task also indicated a significant interaction with tutorial type, favouring the video. The success of the video tutorial is ascribed to its design, which attended to and even incorporated key qualities of paper‐based tutorials, while also capitalizing on the strengths of video.
Morphological changes of the peripheral nerves evaluated by high‐resolution ultrasonography are associated with the severity of diabetic neuropathy, but not corneal nerve fiber pathology in patients with type 2 diabetes
Authors: Ishibashi Fukashi , Taniguchi Miki , Kojima Rie , Kawasaki Asami , Kosaka Aiko , Uetake Harumi
Published: October 2014

Aims/Introduction

To evaluate the morphological changes of the median and posterior tibial nerve using high‐resolution ultrasonography, and the corneal C fiber pathology by corneal confocal microscopy in type 2 diabetic patients.

Materials and Methods

The cross‐sectional area, hypoechoic area and maximum thickness of the nerve fascicle of both nerves were measured by high‐resolution ultrasonography in 200 type 2 diabetic patients, stratified by the severity of diabetic neuropathy, and in 40 age‐ and sex‐matched controls. These parameters were associated with corneal C fiber pathology visualized by corneal confocal microscopy, neurophysiological tests and severity of diabetic neuropathy.

Results

The cross‐sectional area, hypoechoic area and maximum thickness of the nerve fascicle of both nerves in patients without diabetic neuropathy were larger than those in control subjects (P < 0.05 to P < 0.001), and further increased relative to the severity of neuropathy (P < 0.0001). All morphological changes of both nerves were negatively associated with motor and sensory nerve conduction velocity (P = 0.01 to P < 0.0001), and directly associated with 2,000‐Hz current perception threshold (P = 0.009 to P < 0.001). The significant corneal C fiber pathology occurred before developing the neuropathy, and deteriorated only in patients with the most severe neuropathy. The association between the morphological changes of both nerves and corneal C fiber pathology was poor.

Conclusions

The morphological changes in peripheral nerves of type 2 diabetic patients were found before the onset of neuropathy, and were closely correlated with the severity of diabetic neuropathy, but not with corneal C fiber pathology.
Spectophotometric intracutaneous analysis: an investigation on photodamaged skin of immunocompromised patients
Authors: Stimpfle D.W. , Serra A.L. , Wüthrich R.P. , French L.E. , Braun R.P. , Hofbauer G.F.L.
Published: October 2014

Background

SIAscopy (Spectrophotometric Intracutaneous Analysis) enables non‐invasive analysis of the skin.

Objective

We wanted to determine whether SIAscopy is able to detect and differentiate the skin chromophores melanin, collagen and haemoglobin and the influence of immunosuppressive drugs and other known risk factors for non‐melanoma skin cancer (NMSC).

Methods

Volunteers and patients were measured by SIAscopy at six spots on sun‐exposed and two spots on sun‐protected skin. Measurements were transformed by SIAmetrics into arbitrary units and statistically analysed.

Results

Melanin was shown to be higher with age (+1.73759 a.u.; P < 0.0001), sun exposure (+47.03998 a.u.; P < 0.0001), immunosuppression (+10.48526 a.u.; P < 0.0001) and lower in males (−26.50952 a.u.; P < 0.0001). Collagen was lower with increasing age (−0.29162 a.u.; P < 0.0001) and sun exposure (−6.85586 a.u.; P < 0.0001) but higher with male sex (+8.34251 a.u.; P < 0.0001) and immunosuppression (+5.79171 a.u.; P = 0.0001). Haemoglobin was lower with increasing age (−0.23833 a.u.; P = 0.0005), but higher with male sex (+18.51976 a.u.; P < 0.0001) and sun exposure (+13.74523 a.u.; P < 0.0001). Haemoglobin content was not associated to immunosuppression.

Conclusion

Our results encourage the use of SIAscopy as a tool to better gauge an individual patient's NMSC risk factors. Further studies should help to better delineate SIAscopy as a prognostic tool.
The tectono‐metamorphic evolution of the very low‐grade hangingwall constrains two‐stage gneiss dome formation in the Montagne Noire (Southern France)
Authors: Doublier M. P. , Potel S. , Wemmer K.
Published: October 2014

The Montagne Noire in the southernmost French Massif Central is made of an ENE‐elongated gneiss dome flanked by Palaeozoic sedimentary rocks. The tectonic evolution of the gneiss dome has generated controversy for more than half a century. As a result, a multitude of models have been proposed that invoke various tectonic regimes and exhumation mechanisms. Most of these models are based on data from the gneiss dome itself. Here, new constraints on the dome evolution are provided based on a combination of very low‐grade petrology, K–Ar geochronology, field mapping and structural analysis of the Palaeozoic western Mont Peyroux and Faugères units, which constitute part of the southern hangingwall of the dome. It is shown that southward‐directed Variscan nappe‐thrusting (D1) and a related medium‐P metamorphism (M1) are only preserved in the area furthest away from the gneiss dome. The regionally dominant pervasive tectono‐metamorphic event D2/M2 largely transposes D1 structures, comprises a higher metamorphic thermal gradient than M1 (transition low‐P and medium‐P metamorphic facies series) and affected the rocks between c. 309 and 300 Ma, post‐dating D1/M1 by more than 20 Ma. D2‐related fabrics are refolded by D3, which in its turn, is followed by dextral‐normal shearing along the basal shear zone of both units at c. 297 Ma. In the western Mont Peyroux and Faugères units, D2/M2 is largely synchronous with shearing along the southern dome margin between c. 311 and 303 Ma, facilitating the emplacement of the gneiss dome into the upper crust. D2/M2 also overlaps in time with granitic magmatism and migmatization in the Zone Axiale between c. 314 and 306 Ma, and a related low‐P/high‐T metamorphism at c. 308 Ma. The shearing that accompanied the exhumation of the dome therefore was synchronous with a peak in temperature expressed by migmatization and intrusion of melts within the dome, and also with the peak of metamorphism in the hangingwall. Both, the intensity of D2 fabrics and the M2 metamorphic grade within the hangingwall, decrease away from the gneiss dome, with grades ranging from the anchizone–epizone boundary to the diagenetic zone. The related zonation of the pre‐D3 metamorphic field gradients paralleled the dome. These observations indicate that D2/M2 is controlled by the exhumation of the Zone Axiale, and suggest a coherent kinematic between the different crustal levels at some time during D2/M2. Based on integration of these findings with regional geological constraints, a two‐stage exhumation of the gneiss dome is proposed: during a first stage between c. 316 and 300 Ma dome emplacement into the upper crust was controlled by dextral shear zones arranged in a pull‐apart‐like geometry. The second stage from 300 Ma onwards was characterized by northeast to northward extension, with exhumation accommodated by north‐dipping detachments and hangingwall basin formation along the northeastern dome margin.
Evaluation of Rotational Vertebral Artery Occlusion Using Ultrasound Facilitates the Detection of Arterial Dissection in the Atlas Loop
Authors: Yamaoka Y. , Ichikawa Y. , Morita A.
Published: October 2014

PURPOSE

Head rotation can cause occlusion of the vertebral artery most commonly at the atlas loop, and repetitive compression from head turning induces vertebral artery dissection (VAD). Although ultrasound examinations are useful in diagnosis, dissected lesions unaccompanied by hemodynamic changes can be overlooked. Because the narrowed, dissected vessel in the atlas loop may cause rotational occlusion, we confirmed whether adding submaximal head rotation to a cervical ultrasound examination would facilitate the detection of VAD in the atlas loop.

METHODS

We investigated 7 patients who developed infarction in the posterior circulation and were clinically suspected of VAD. Using a 7.5‐MHz linear probe, we recorded the waveform of the vertebral artery at the C4‐C6 level and diagnosed rotational vertebral artery occlusion (RVAO) when head rotation induced the disappearance of end‐diastolic flow.

RESULTS

All 3 patients with VAD in the atlas loop demonstrated RVAO of the dissected vertebral arteries in the acute stroke phase. RVAO was not observed in the dissected vertebral arteries excepting the atlas loop, nor in the nondissected vertebral arteries of any patients.

CONCLUSION

For posterior circulation stroke patients, adding submaximal head rotation to the cervical ultrasound examination facilitated the detection of VAD in the atlas loop.
Novel Approaches in Evaluating and Predicting the Potential Benefit of Middle Cerebral Artery Angioplasty & Stenting
Authors: Zi Wenjie , Gong Zili , Shuai Jie
Published: October 2014

OBJECTIVE

Our aim was to investigate a novel approach to perform preoperative evaluation patients who underwent middle cerebral artery (MCA) percutaneous transluminal angioplasty and stenting (PTAS).

METHOD

Sixty‐five patients with symptomatic MCA stenosis of at least >70% who underwent MCA PTAS were enrolled. The multimodal stroke assessment using CT (MOSAIC) score was used to evaluate the preoperative condition. The Alberta Stroke Program Early Computed Tomography Scoring (ASPECTS) was used to assess the time‑to‑peak (TTP) parameter of Computer tomography perfusion (CTP). The factors potentially improving TTP following stenting were investigated. The prognostic value of the MOSAIC scores to predict TTP improvement was analyzed and compared.

RESULTS

The MOSAIC score was a reliable prognostic tool for the degree of improvement of TTP (odds ratio 1.89 [1.08‐2.07], P < .01) in patients with PTAS. The MOSAIC score had a higher prognostic accuracy than the degree of CBF deficit, the degree of stenosis, and the amount of tissue infarction. During 1‐year follow‐up, the stroke and death rate of was 8.1%, the in‐stent restenosis rate was 6.5%, and good final outcome (modified Rankin Scale ≤ 2) was observed in 76.9%.

CONCLUSIONS

The MOSAIC score can be reliably used in selecting patients with MCA stenosis for PTAS.
Brain Atrophy in Radiologically Isolated Syndromes
Authors: Rojas Juan Ignacio , Patrucco Liliana , Míguez Jimena , Besada Cristina , Cristiano Edgardo
Published: October 2014

INTRODUCTION

The aim of this study was to compare brain atrophy in radiologically isolated syndrome (RIS), in clinically isolated syndrome (CIS), and in individuals with subjective complaints (ISC).

METHODS

Patients with RIS were included prospectively during June 2009 to June 2012. CIS patients and ISC were used to compare the RIS sample. An automated analysis tool, SIENAX, was used to obtain normalized total brain volume (NTBV), normalized cortical volume (NCV), and normalized white matter volume (NWMV). ANOVA test was used to analyze the data.

RESULTS

A total of 10 RIS patients, 43 CIS patients, and 29 ISC were included. The NTBV in RIS was 1.56 mm3 × 106, 1.52 × 106 in CIS, and 1.64 × 106 in ISC (P = .12 vs. CIS and P = .003 vs. ISC); the NCV in RIS was .59 × 106, .55 × 106 in CIS, and .71 × 106 in ISC (P = .22 vs. CIS and P = .002 vs. ISC), and NWMV in RIS was 1.1 × 106, 1 in CIS and 1.12 × 106 in ISC (P = .66 vs. CIS and P = .12 vs. ISC).

CONCLUSIONS

NTBV and NCV were significantly lower in RIS compared with ISC while no differences were observed in NWMV.
Improving masticatory performance, bite force, nutritional state and patient's satisfaction with implant overdentures: a systematic review of the literature
Authors: Boven G. C. , Raghoebar G. M. , Vissink A. , Meijer H. J. A.
Published: October 2014

Oral function with removable dentures is improved when dental implants are used for support. A variety of methods is used to measure change in masticatory performance, bite force, patient's satisfaction and nutritional state. A systematic review describing the outcome of the various methods to assess patients' appreciation has not been reported. The objective is to systematically review the literature on the possible methods to measure change in masticatory performance, bite force, patient's satisfaction and nutritional state of patients with removable dentures and to describe the outcome of these. Medline, Embase and The Cochrane Central Register of Controlled Trials were searched (last search July 1, 2014). The search was completed by hand to identify eligible studies. Two reviewers independently assessed the articles. Articles should be written in English. Study design should be prospective. The outcome should be any assessment of function/satisfaction before and at least 1 year after treatment. Study population should consist of fully edentulous subjects. Treatment should be placement of any kind of root‐form implant(s) to support a mandibular and/or maxillary overdenture. Fifty‐three of 920 found articles fulfilled the inclusion criteria. A variety of methods was used to measure oral function; mostly follow‐up was 1 year. Most studies included mandibular overdentures, three studies included maxillary overdentures. Implant‐supported dentures were accompanied by high patient's satisfaction with regard to denture comfort, but this high satisfaction was not always accompanied by improvement in general quality of life (QoL) and/or health‐related QoL. Bite force improved, masseter thickness increased and muscle activity in rest decreased. Patients could chew better and eat more tough foods. No changes were seen in dietary intake, BMI and blood markers. Improvements reported after 1 year apparently decreased slightly with time, at least on the long run. Treating complete denture wearers with implants to support their denture improves their chewing efficiency, increases maximum bite force and clearly improves satisfaction. The effect on QoL is uncertain, and there is no effect on nutritional state.
Evidence‐Based Criteria for Differential Treatment Planning of Implant Restorations for the Maxillary Edentulous Patient
Authors: Sadowsky Steven J. , Fitzpatrick Brian , Curtis Donald A.
Published: October 2014

Since the introduction of the endosseous concept to North America in 1982, there have been new permutations of the original ad modum Branemark design to meet the unique demands of treating the edentulous maxilla with an implant restoration. While there is a growing body of clinical evidence to assist the student, faculty, and private practitioner in the algorithms for design selection, confusion persists because of difficulty in assessing the external and internal validity of the relevant studies. The purpose of this article is to review clinician‐ and patient‐mediated factors for implant restoration of the edentulous maxilla in light of the hierarchical level of available evidence, with the aim of elucidating the benefit/risk calculus of various treatment modalities.