bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein O-GlcNAcylation Is a Novel Cytoprotective Signal in Cardiac Stem Cells
Authors: Zafir Ayesha , Readnower Ryan , Long Bethany W. , McCracken James , Aird Allison , Alvarez Alejandro , Cummins Timothy D. , Li Qianhong , Hill Bradford G. , Bhatnagar Aruni , Prabhu Sumanth D. , Bolli Roberto , Jones Steven P.
Published: January 2013

Clinical trials demonstrate the regenerative potential of cardiac stem cell (CSC) therapy in the postinfarcted heart. Despite these encouraging preliminary clinical findings, the basic biology of these cells remains largely unexplored. The principal requirement for cell transplantation is to effectively prime them for survival within the unfavorable environment of the infarcted myocardium. In the adult mammalian heart, the β-O-linkage of N-acetylglucosamine (i.e., O-GlcNAc) to proteins is a unique post-translational modification that confers cardioprotection from various otherwise lethal stressors. It is not known whether this signaling system exists in CSCs. In this study, we demonstrate that protein O-GlcNAcylation is an inducible stress response in adult murine Sca-1+/lin− CSCs and exerts an essential prosurvival role. Posthypoxic CSCs responded by time-dependently increasing protein O-GlcNAcylation upon reoxygenation. We used pharmacological interventions for loss- and gain-of-function, that is, enzymatic inhibition of O-GlcNAc transferase (OGT) (adds the O-GlcNAc modification to proteins) by TT04, or inhibition of OGA (removes O-GlcNAc) by thiamet-G (ThG). Reduction in the O-GlcNAc signal (via TT04, or OGT gene deletion using Cre-mediated recombination) significantly sensitized CSCs to posthypoxic injury, whereas augmenting O-GlcNAc levels (via ThG) enhanced cell survival. Diminished O-GlcNAc levels render CSCs more susceptible to the onset of posthypoxic apoptotic processes via elevated poly(ADP-ribose) polymerase cleavage due to enhanced caspase-3/7 activation, whereas promoting O-GlcNAcylation can serve as a pre-emptive antiapoptotic signal regulating the survival of CSCs. Thus, we report the primary demonstration of protein O-GlcNAcylation as an important prosurvival signal in CSCs, which could enhance CSC survival prior to in vivo autologous transfer.
IGF1 Receptor Signaling Regulates Adaptive Radioprotection in Glioma Stem Cells
Authors: Osuka Satoru , Sampetrean Oltea , Shimizu Takatsune , Saga Isako , Onishi Nobuyuki , Sugihara Eiji , Okubo Jun , Fujita Satoshi , Takano Shingo , Matsumura Akira , Saya Hideyuki
Published: January 2013

Cancer stem cells (CSCs) play an important role in disease recurrence after radiation treatment as a result of intrinsic properties such as high DNA repair capability and antioxidative capacity. It is unclear, however, how CSCs further adapt to escape the toxicity of the repeated irradiation regimens used in clinical practice. Here, we have exposed a population of murine glioma stem cells (GSCs) to fractionated radiation in order to investigate the associated adaptive changes, with the ultimate goal of identifying a targetable factor that regulates acquired radioresistance. We have shown that fractionated radiation induces an increase in IGF1 secretion and a gradual upregulation of the IGF type 1 receptor (IGF1R) in GSCs. Interestingly, IGF1R upregulation exerts a dual radioprotective effect. In the resting state, continuous IGF1 stimulation ultimately induces downregulation of Akt/extracellular-signal-regulated kinases (ERK) and FoxO3a activation, which results in slower proliferation and enhanced self-renewal. In contrast, after acute radiation, the abundance of IGF1R and increased secretion of IGF1 promote a rapid shift from a latent state toward activation of Akt survival signaling, protecting GSCs from radiation toxicity. Treatment of tumors formed by the radioresistant GSCs with an IGF1R inhibitor resulted in a marked increase in radiosensitivity, suggesting that blockade of IGF1R signaling is an effective strategy to reverse radioresistance. Together, our results show that GSCs evade the damage of repeated radiation not only through innate properties but also through gradual inducement of resistance pathways and identify the dynamic regulation of GSCs by IGF1R signaling as a novel mechanism of adaptive radioprotection.
The CD44+ALDH+ Population of Human Keratinocytes Is Enriched for Epidermal Stem Cells with Long-Term Repopulating Ability
Authors: Szabo Akos Z. , Fong Stephen , Yue Lili , Zhang Kai , Strachan Lauren R. , Scalapino Kenneth , Mancianti Maria Laura , Ghadially Ruby
Published: January 2013

Like for other somatic tissues, isolation of a pure population of stem cells has been a primary goal in epidermal biology. We isolated discrete populations of freshly obtained human neonatal keratinocytes (HNKs) using previously untested candidate stem cell markers aldehyde dehydrogenase (ALDH) and CD44 as well as the previously studied combination of integrin α6 and CD71. An in vivo transplantation assay combined with limiting dilution analysis was used to quantify enrichment for long-term repopulating cells in the isolated populations. The ALDH+CD44+ population was enriched 12.6-fold for long-term repopulating epidermal stem cells (EpiSCs) and the integrin α6hiCD71lo population was enriched 5.6-fold, over unfractionated cells. In addition to long-term repopulation, CD44+ALDH+ keratinocytes exhibited other stem cell properties. CD44+ALDH+ keratinocytes had self-renewal ability, demonstrated by increased numbers of cells expressing nuclear Bmi-1, serial transplantation of CD44+ALDH+ cells, and holoclone formation in vitro. CD44+ALDH+ cells were multipotent, producing greater numbers of hair follicle-like structures than CD44−ALDH− cells. Furthermore, 58% ± 7% of CD44+ALDH+ cells exhibited label-retention. In vitro, CD44+ALDH+ cells showed enhanced colony formation, in both keratinocyte and embryonic stem cell growth media. In summary, the CD44+ALDH+ population exhibits stem cell properties including long-term epidermal regeneration, multipotency, label retention, and holoclone formation. This study shows that it is possible to quantify the relative number of EpiSCs in human keratinocyte populations using long-term repopulation as a functional test of stem cell nature. Future studies will combine isolation strategies as dictated by the results of quantitative transplantation assays, in order to achieve a nearly pure population of EpiSCs.
On loops in inflation II: IR effects in single clock inflation
Authors: Senatore Leonardo , Zaldarriaga Matias
Published: January 2013

Abstract

In single clock models of inflation the coupling between modes of very different scales does not have any significant dynamical effect during inflation. It leads to interesting projection effects. Larger and smaller modes change the relation between the scale a mode of interest will appear in the post-inflationary universe and will also change the time of horizon crossing of that mode. We argue that there are no infrared projection effects in physical questions, that there are no effects from modes of longer wavelength than the one of interest at the time of reheating. These potential effects cancel when computing fluctuations as a function of physically measurable scales. Modes on scales smaller than the one of interest change the mapping between horizon crossing time and scale. The correction to the mapping computed in the absence of fluctuations is enhanced by a factor N
e, the number of e-folds of inflation between horizon crossing and reheating. The new mapping is stochastic in nature but its variance is not enhanced by N
e.
Ungauging black holes and hidden supercharges
Authors: Hristov Kiril , Katmadas Stefanos , Pozzoli Valentina
Published: January 2013

Abstract

We embed the general solution for non-BPS extremal asymptotically flat static and under-rotating black holes in abelian gauged D = 4
$ \mathcal{N}=2 $
supergravity, in the limit where the scalar potential vanishes but the gauging does not. Using this result, we show explicitly that some supersymmetries are preserved in the near horizon region of all the asymptotically flat solutions above, in the gauged theory. This reveals a deep relation between microscopic entropy counting of extremal black holes in Minkowski and BPS black holes in AdS. Finally, we discuss the relevance of this construction to the structure of asymptotically AdS4 black holes, as well as the possibility of including hypermultiplets.
Holographic interpretations of the renormalization group
Authors: Balasubramanian Vijay , Guica Monica , Lawrence Albion
Published: January 2013

Abstract

In semiclassical holographic duality, the running couplings of a field theory are conventionally identified with the classical solutions of field equations in the dual gravitational theory. However, this identification is unclear when the bulk fields fluctuate. Recent work has used a Wilsonian framework to propose an alternative identification of the running couplings in terms of non-fluctuating data; in the classical limit, these new couplings do not satisfy the bulk equations of motion. We study renormalization scheme dependence in the latter formalism, and show that a scheme exists in which couplings to single trace operators realize particular solutions to the bulk equations of motion, in the semiclassical limit. This occurs for operators with dimension
$ \varDelta \notin \frac{d}{2}+\mathbb{Z} $
, for sufficiently low momenta. We then clarify the relation between the saddle point approximation to the Wilsonian effective action (S

W
) and boundary conditions at a cutoff surface in AdS space. In particular, we interpret non-local multi-trace operators in S

W
as arising in Lorentzian AdS space from the temporary passage of excitations through the UV region that has been integrated out. Coarse-graining these operators makes the action effectively local.
The need for a canopy perspective to understand the importance of phenotypic plasticity for promoting species coexistence and light‐use complementarity in forest ecosystems
Authors: Ishii Hiroaki , Azuma Wakana , Nabeshima Eri
Published: January 2013

Because of their overwhelming size over other organisms, trees define the structural and energetic properties of forest ecosystems. From grasslands to forests, leaf area index, which determines the amount of light energy intercepted for photosynthesis, increases with increasing canopy height across the various terrestrial ecosystems of the world. In vertically well‐developed forests, niche differentiation along the vertical gradient of light availability may promote species coexistence. In addition, spatial and temporal differentiation of photosynthetic traits among the coexisting tree species (functional diversity) may promote complementary use of light energy, resulting in higher biomass and productivity in multi‐species forests. Trees have evolved retaining high phenotypic plasticity because the spatial/temporal distribution of resources in forest ecosystems is highly heterogeneous and trees modify their own environment as they increase nearly 1,000 times in size through ontogeny. High phenotypic plasticity may enable coexistence of tree species through divergence in resource‐rich environments, as well as through convergence in resource‐limited environments. We propose that the breadth of individual‐level phenotypic plasticity, expressed at the metamer level (leaves and shoots), is an important factor that promotes species coexistence and resource‐use complementarity in forest ecosystems. A cross‐biome comparison of the link between plasticity of photosynthesis‐related traits and stand productivity will provide a functional explanation for the relationship between species assemblages and productivity of forest ecosystems.
Weak mismatch epitaxy and structural Feedback in graphene growth on copper foil
Authors: Wilson Neil R. , Marsden Alexander J. , Saghir Mohammed , Bromley Catherine J. , Schaub Renald , Costantini Giovanni , White Thomas W. , Partridge Cerianne , Barinov Alexei , Dudin Pavel , Sanchez Ana M. , Mudd James J. , Walker Marc , Bell Gavin R.
Published: January 2013

Graphene growth by low-pressure chemical vapor deposition on low cost copper foils shows great promise for large scale applications. It is known that the local crystallography of the foil influences the graphene growth rate. Here we find an epitaxial relationship between graphene and copper foil. Interfacial restructuring between graphene and copper drives the formation of (n10) facets on what is otherwise a mostly Cu(100) surface, and the facets in turn influence the graphene orientations from the onset of growth. Angle resolved photoemission shows that the electronic structure of the graphene is decoupled from the copper indicating a weak interaction between them. Despite this, two preferred orientations of graphene are found, ±8° from the Cu[010] direction, creating a non-uniform distribution of graphene grain boundary misorientation angles. Comparison with the model system of graphene growth on single crystal Cu(110) indicates that this orientational alignment is due to mismatch epitaxy. Despite the differences in symmetry the orientation of the graphene is defined by that of the copper. We expect these observations to not only have importance for controlling and understanding the growth process for graphene on copper, but also to have wider implications for the growth of two-dimensional materials on low cost metal substrates.
Differential roles of miR‐199a‐5p in radiation‐induced autophagy in breast cancer cells
Authors: Yi Heqing , Liang Bing , Jia Jie , Liang Nan , Xu Huiying , Ju Guizhi , Ma Shumei , Liu Xiaodong
Published: January 2013

Autophagy is a self‐degrading process that is triggered by diverse stimuli including ionizing radiation. In this study we show novel phenomena in which transfection of miR‐199a‐5p mimic significantly suppresses IR‐induced autophagy in MCF7 cells, and up‐regulates basal and IR‐induced autophagy in MDA‐MB‐231 breast cancer cells. We also identify DRAM1 and Beclin1 as novel target genes for miR‐199a‐5p. Overexpression of miR‐199a‐5p inhibits DRAM1 and Beclin1 expression in MCF7 cells, while it enhances expression of these genes in MDA‐MB‐231 cells. Furthermore, we show that miR‐199a‐5p sensitizes MDA‐MB‐231 cells to irradiation. Therefore, our data identify miR‐199a‐5p as a novel and unique regulator of autophagy, which plays an important role in cancer biology and cancer therapy.
Genome‐wide characterization of the relationship between essential and TATA‐containing genes
Authors: Han Hyun Wook , Bae Sang Hun , Jung Yun Hwa , Moon Jisook
Published: January 2013

Essential genes are involved in most survival‐related housekeeping functions. TATA‐containing genes encode proteins involved in various stress–response functions. However, because essential and TATA‐containing genes have been researched independently, their relationship remains unclear. The present study classified Saccharomyces cerevisiae genes into four groups: non‐essential non‐TATA, non‐essential TATA, essential non‐TATA, and essential TATA genes. The results showed that essential TATA genes have the most significant codon bias, the highest level of expression, and unique characteristics, including a large number of transcription factor binding sites, a higher degree in protein interaction networks, and significantly different amino acid usage patterns compared with the other gene groups. Notably, essential TATA genes were uniquely involved in functions such as unfolded protein binding, glycolysis, and alcohol and steroid‐related processes.
Formation of protein complexes in crowded environments – From in vitro to in vivo
Authors: Phillip Yael , Schreiber Gideon
Published: January 2013

Traditionally, biochemical studies are performed in dilute homogenous solutions, which are very different from the dense mixture of molecules found in cells. Thus, the physiological relevance of these studies is in question. This recognition motivated scientists to formulate the effect of crowded solutions in general, and excluded volume in particular, on biochemical processes. Using polymers or proteins as crowders, it was shown that while crowding tends to significantly enhance the formation of complexes containing many subunits, dimerizations are only mildly affected. Computer simulations, together with experimental evidence, indicate soft interactions and diffusion as critical factors that operate in a concerted manner with excluded volume to modulate protein binding. Yet, these approaches do not truly mimic the cellular environment. In vivo studies may overcome this shortfall. The few studies conducted thus far suggest that in cells, binding and folding occur at rates close to those determined in dilute solutions. Obtaining quantitative biochemical information on reactions inside living cells is currently a main challenge of the field, as the complexity of the intracellular milieu was what motivated crowding research to begin with.
Identification and characterization of PtDGAT2B, an acyltransferase of the DGAT2 acyl‐Coenzyme A: Diacylglycerol acyltransferase family in the diatom Phaeodactylum tricornutum
Authors: Gong Yangmin , Zhang Junping , Guo Xiaojing , Wan Xia , Liang Zhuo , Hu Chuan Jiong , Jiang Mulan
Published: January 2013

Diacylglycerol acyltransferase (DGAT) plays a pivotal role in triacylglycerol (TAG) formation in some oleaginous organisms. We describe here the identification of a type 2 DGAT (PtDGAT2B) in the diatom Phaeodactylum tricornutum that contains four putative type 2 acyl‐CoA:DGATs, sharing little sequence similarity with each other. TAG synthesis and lipid body formation could be completely restored in a Saccharomyces cerevisiae TAG‐deficient quadruple mutant by expressing PtDGAT2B. Up‐regulation of PtDGAT2B precedes the accumulation of TAG. Functional analysis of enzyme activity in vivo demonstrated that expression of PtDGAT2B can increase the proportion of unsaturated C16 and C18 fatty acids in yeast TAG.
MiR‐214 reduces cell survival and enhances cisplatin‐induced cytotoxicity via down‐regulation of Bcl2l2 in cervical cancer cells
Authors: Wang Fang , Liu Min , Li Xin , Tang Hua
Published: January 2013

MiR‐214 has been shown to inhibit cell growth, migration and invasion. Here we demonstrate that ectopic expression of miR‐214 reduces cell survival, induces apoptosis and enhances sensitivity to cisplatin through directly inhibiting Bcl2l2 expression in cervical cancer HeLa and C‐33A cells. Further analysis reveals that apoptosis induced by miR‐214 is correlated with increased expression of Bax, caspase‐9, caspase‐8 and caspase‐3. Moreover, we show that miR‐214 is regulated by DNA methylation and histone deacetylation. Taken together, these data suggest that miR‐214 might be a candidate target for the development of novel therapeutic strategies to treat cervical cancer.
Correlation of Paraspinal Atrophy and Denervation in Back Pain and Spinal Stenosis Relative to Asymptomatic Controls
Authors: Yarjanian John A. , Fetzer April , Yamakawa Karen S. , Tong Henry C. , Smuck Matthew , Haig Andrew
Published: January 2013

Objective

To determine the relationship among spinal stenosis, back pain, paraspinal muscle denervation, and paraspinal muscle atrophy.

Design

A prospective masked, double‐controlled study.

Setting

A university hospital and outpatient spine clinic.

Participants

Ten asymptomatic subjects, 10 subjects with mechanical low back pain, and 15 subjects with symptomatic spinal stenosis; age range, 55‐80 years old.

Interventions

Magnetic resonance imaging measurements of minimum spinal canal diameter, paraspinal muscle cross‐sectional area at the level of the L5‐S1 disk, and quantified paraspinal electrodiagnostic testing (MiniPM) were performed by examiners blinded to each other's results and to the participants' clinical information.

Main Outcome Measurements

Paraspinal muscle cross‐sectional area and MiniPM scores.

Results

A paraspinal cross‐sectional area decreased significantly from asymptomatic subjects (3872 mm2) to subjects with low back pain (3627 mm2) and to subjects with spinal stenosis (2985 mm2). In the stenosis group, there was a trend toward increased paraspinal denervation in the subjects with severe spinal stenosis, but this was not statistically significant.

Conclusions

Symptomatic spinal stenosis results in greater paraspinal muscle atrophy than low back pain alone. The extent of paraspinal atrophy was not significantly explained by the extent of denervation, thus, it may be reversible, and the role of paraspinal muscle rehabilitation in patients with spinal stenosis deserves further study.
ON A SEQUENCE INVOLVING SUMS OF PRIMES
Authors: SUN ZHI-WEI
Published: January 2013

For $n= 1, 2, 3, \ldots $ let ${S}_{n} $ be the sum of the first $n$ primes. We mainly show that the sequence ${a}_{n} = \sqrt[n]{{S}_{n} / n}~(n= 1, 2, 3, \ldots )$ is strictly decreasing, and moreover the sequence ${a}_{n+ 1} / {a}_{n} ~(n= 10, 11, \ldots )$ is strictly increasing. We also formulate similar conjectures involving twin primes or partitions of integers.
LIPSCHITZ SPACES AND BOUNDED MEAN OSCILLATION OF HARMONIC MAPPINGS
Authors: CHEN SH. , PONNUSAMY S. , VUORINEN M. , WANG X.
Published: January 2013

We first study the bounded mean oscillation of planar harmonic mappings. Then we establish a relationship between Lipschitz-type spaces and equivalent modulus of real harmonic mappings. Finally, we obtain sharp estimates on the Lipschitz number of planar harmonic mappings in terms of the bounded mean oscillation norm, which shows that the harmonic Bloch space is isomorphic to$BM{O}_{2} $as a Banach space.
Crisis Bargaining and Nuclear Blackmail
Authors: Sechser Todd S. , Fuhrmann Matthew
Published: January 2013

Do nuclear weapons offer coercive advantages in international crisis bargaining? Almost seventy years into the nuclear age, we still lack a complete answer to this question. While scholars have devoted significant attention to questions about nuclear deterrence, we know comparatively little about whether nuclear weapons can help compel states to change their behavior. This study argues that, despite their extraordinary power, nuclear weapons are uniquely poor instruments of compellence. Compellent threats are more likely to be effective under two conditions: first, if a challenger can credibly threaten to seize the item in dispute; and second, if enacting the threat would entail few costs to the challenger. Nuclear weapons, however, meet neither of these conditions. They are neither useful tools of conquest nor low-cost tools of punishment. Using a new dataset of more than 200 militarized compellent threats from 1918 to 2001, we find strong support for our theory: compellent threats from nuclear states are no more likely to succeed, even after accounting for possible selection effects in the data. While nuclear weapons may carry coercive weight as instruments of deterrence, it appears that these effects do not extend to compellence.
Combined mineral N and organic waste fertilization – effects on crop growth and soil properties
Authors: ODLARE M. , PELL M. , ARTHURSON J. V. , ABUBAKER J. , NEHRENHEIM E.
Published: January 2013

An 8-year-long field experiment (1998–2006) was established in Sweden with the aim of evaluating the effects of applying organic wastes in combination with mineral nitrogen (N) to agricultural soil. Sewage sludge (SS), biogas residues (BR) and municipal compost (CO) were applied annually at rates corresponding to 50 kg N/ha and supplementary mineral N fertilizer also applied at rates corresponding to 50 kg N/ha. The effects were evaluated by analysing crop yield and soil chemical and microbiological properties. The results showed that none of the fertilizers produced significantly higher yield of barley over the 8-year period compared to any other. Biogas residue proved to be particularly beneficial for the substrate-induced respiration (SIR) in soil and increased the proportion of active to dormant micro-organisms. Treatment with SS increased plant-available phosphorus (P-AL) and N mineralization (N-min), whereas CO increased the basal respiration (B-resp). Changes in the microbial community structure were assayed by terminal restriction fragment length polymorphism (T-RFLP); the T-RFLP signatures of the soil bacterial community were largely unaffected by the addition of organic waste. Of the chemical properties assayed, the largest increases were seen in P-AL, where SS produced the highest value. Treatments with the organic wastes showed no negative effects other than a slight decrease in B-resp induced by SS and BR. In conclusion, the microbiological activity in the soil responded more rapidly than the changes in the community structure and the chemical properties to changes in the soil environment.
Influence of ultrasound on chemically induced gelation of micellar casein systems
Authors: Chandrapala Jayani , Zisu Bogdan , Kentish Sandra , Ashokkumar Muthupandian
Published: January 2013

Gelation is a significant operation in dairy processing. Protein gelation can be affected by several factors such as temperature, pH, or enzyme addition. Recently, the use of ultrasonication has been shown to have a significant impact on the formation of whey protein gels. In this work, the effect of ultrasonication on the gelation of casein systems was investigated. Gels were formed by the addition of 7·6 mm Tetra Sodium Pyro Phosphate (TSPP) to 5 wt% micellar casein (MC) solutions. Sonication at 20 KHz and 31 W for up to 30 min changed the surface hydrophobicity of the proteins, whereas surface charge was unaltered. Sonication before the addition of TSPP formed a firm gel with a fine protein network and low syneresis. Conversely, sonication after TSPP addition led to an inconsistent weak-gel-like structure with high syneresis. Gel strength in both cases increased significantly after short sonication times, while the viscoelastic properties were less affected. Overall, the results showed that ultrasonication can have a significant effect on the final gel properties of casein systems.
Role of Langerhans cells, Ki-67 protein and apoptosis in acquired cholesteatoma: prospective clinical study
Authors: Akdogan V , Yilmaz I , Canpolat T , Ozluoglu L N
Published: January 2013

Objective:

To investigate the role of Langerhans cells in the pathogenesis and clinical picture of middle-ear cholesteatoma.

Subjects and methods:

The study included 40 patients operated upon for a diagnosis of chronic otitis due to acquired cholesteatoma.

Results and analysis:

A closed surgical technique was used in 20 per cent of patients and an open technique in 80 per cent. Langerhans cells were more densely accumulated in cholesteatoma epithelium, compared with external ear canal skin (p < 0.001). Staining for Ki-67 protein was greater in cholesteatoma epithelium (p < 0.001) and Apo2.7 protein staining (indicating apoptosis) was more prominent (p < 0.001), compared with ear canal skin. Regarding significant relationships between clinical and pathological findings, staining for Ki-67 (p = 0.046) and Apo2.7 (p = 0.037) was more prominent in patients undergoing open versus closed surgery.

Conclusion:

Using cell proliferation and apoptosis markers, a dense Langerhans cell infiltration was found to occur as a host response to middle-ear cholesteatoma.
KING HENRY I AND NORTHERN ENGLAND
Authors: Green Judith
Published: January 2013

England north of the Humber and the Mersey in the early twelfth century has in the past tended to be discussed in the context of the development of the monarchy. The Normans moved into the northern counties later and in fewer numbers than the south, and in the wake of the Norman settlement the north came to be more fully integrated into the southern kingdom. A fresh perspective on the period is gained by comparing Henry I's rule over the north with that in other regions of England, Wales and Normandy. Its keys were old-style dynastic politics and patronage, and his achievement that of bringing peace to the region.
ARISTOCRATIC WIDOWS AND THE MEDIEVAL WELSH FRONTIER: THE SHROPSHIRE EVIDENCE
Authors: Cavell Emma
Published: January 2013

This article builds upon the work of the late Professor Sir Rees Davies and other scholars interested in the medieval March of Wales, and draws attention to the place, roles and experiences of the noblewomen in a region usually considered the preserve of the warrior lord. In focusing on the aristocratic widow, for whom records are relatively abundant, it examines the widows’ experience of dower assignment and of estate and castle management on a frontier district. It contends that, among other things, those who allocated dower to the widows of the region deliberately eschewed the frontier hotspots, and that the normative relationship between female lord and castle was at once improved and restricted by the warlike nature of the region. A final section examines the life and career of the often overlooked Isabel de Mortimer (daughter of Roger de Mortimer of Wigmore and sometime wife of John FitzAlan III), revealing her critical part in holding the Shropshire frontline on the eve of the final conquest of Wales (1282–3). The case is made that we cannot fully understand the aristocratic Marcher society without including women in our histories.
THEODORE VACQUER AND THE ARCHAEOLOGY OF MODERNITY IN HAUSSMANN'S PARIS
Authors: Jones Colin
Published: January 2013

Théodore Vacquer (1824–99) was an archaeologist who excavated, directed excavations in and visited all archaeological sites in Paris between the 1840s and his death. In the latter part of his career, he served as assistant curator at what became the Musée Carnavalet, specialising in the Roman and early medieval history of the city. Taking advantage of the reconstruction of the city in the nineteenth century associated with the work of Paris prefect, Baron Haussmann, he was able to locate far more of Roman Paris than had been known before. His findings remained the basis of what was known about the Roman city until a new wave of archaeological excavations after 1950. Vacquer aimed to highlight his discoveries in a magnum opus on the history of Paris from earliest times to ad 1000, but he died with virtually nothing written. His extensive archive still exists, however, and provides the substance for this essay. The essay seeks to rescue Vacquer from the relative obscurity associated with his name. In addition, by setting his life and work in the context of the Haussmannian construction of Paris as the arch-city of modernity it aims to illuminate the history of archaeology, conservation and urban identity in nineteenth-century Paris.
The L1-norm of exponential sums in d
Authors: PETRIDIS GIORGIS
Published: January 2013

Let A be a finite set of integers and FA(x) = ∑a∈A exp(2πiax) be its exponential sum. McGehee, Pigno and Smith and Konyagin have independently proved that ∥FA∥1 ≥ c log|A| for some absolute constant c. The lower bound has the correct order of magnitude and was first conjectured by Littlewood. In this paper we present lower bounds on the L1-norm of exponential sums of sets in the d-dimensional grid d. We show that ∥FA∥1 is considerably larger than log|A| when A ⊂ d has multidimensional structure. We furthermore prove similar lower bounds for sets in , which in a technical sense are multidimensional and discuss their connection to an inverse result on the theorem of McGehee, Pigno and Smith and Konyagin.
Within-herd prevalence ofSalmonellaDublin in endemically infected dairy herds
Authors: NIELSEN L. R.
Published: January 2013

In this study within-herd prevalence ofSalmonellaDublin was investigated in three age groups (calves, young stock, adult cows) during five herd visits at 3-month intervals of 14 endemically infected dairy herds. A total of 10162 paired faecal cultures and antibody measurements were used to calculate the age and temporal dynamics of seroprevalence and prevalence of positive faecal cultures. Faecal culture-positive prevalence was generally low. It was highest (5·4%) in calves during December to February. Seroprevalence varied from 0% to 70% between herds, but was generally more stable in young stock and adult cows than in calves. Hierarchical mixed-model results showed that seroprevalence was associated with the bacteriological status in calves and cows, but not in young stock. These results can be used to develop and validate theoretical infection dynamics models and to design effective control programmes forSalmonellaDublin in dairy herds.
C-type natriuretic peptide inhibits porcine oocyte meiotic resumption
Authors: Hiradate Yuki , Hoshino Yumi , Tanemura Kentaro , Sato Eimei
Published: January 2013

C-type natriuretic peptide (CNP) is a recently identified meiotic inhibitor in mice. However, it has not been investigated in porcine oocytes to date. This study aimed to demonstrate the inhibitory effect of CNP against germinal vesicle breakdown (GVBD) in porcine oocyte meiotic resumption. Immunohistochemical analysis revealed intense natriuretic peptide receptor 2 (NPR2) immunoreactivity in the oocyte surrounded cumulus cells in the follicles. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) analysis showed the expression of npr2 mRNA only in cumulus cells but not in oocytes, suggesting that cumulus cells are the targets of CNP. When cumulus–oocyte complexes (COCs) or denuded oocytes (DOs) were cultured with various concentrations of CNP (10, 50, 100, 500, and 1,000 nM), inhibitory effect was observed in the COC group, but not in the DO group, confirming that CNP indirectly inhibits GVBD via cumulus cells. This evidence is the first indication that the CNP-NPR2 pathway is involved in meiotic arrest in porcine oocytes. Furthermore, we investigated the effect of oocyte-derived paracrine factor (ODPF) on npr2 mRNA expression level in cumulus cells by evaluating changes in mRNA expression in oocytectomised COCs (OXCs) by real-time PCR. A significant decrease in npr2 mRNA expression level was observed in OXCs, whereas mRNA expression level was restored in OXCs with DOs, indicating that ODPF participates in the regulation of npr2 expression in porcine cumulus cells.
Regulation of embryonic size in early mouse development in vitro culture system
Authors: Hisaki Tomoka , Kawai Ikuma , Sugiura Koji , Naito Kunihiko , Kano Kiyoshi
Published: January 2013

Mammals self-regulate their body size throughout development. In the uterus, embryos are properly regulated to be a specific size at birth. Previously, size and cell number in aggregated embryos, which were made from two or more morulae, and half embryos, which were halved at the 2-cell stage, have been analysed in vivo in preimplantation and post-implantation development in mice. Here, we examined whether or not the mouse embryo has the capacity to self-regulate growth using an in vitro culture system. To elucidate embryonic histology, cells were counted in aggregated or half embryos in comparison with control embryos. Both double- and triple-aggregated embryos contained more cells than did control embryos during all culture periods, and the relative growth ratios showed no growth inhibition in an in vitro culture system. Meanwhile, half embryos contained fewer cells than control embryos, but the number grew throughout the culture period. Our data suggest that the growth of aggregated embryos is not affected and continues in an in vitro culture system. On the other hand, the growth of half embryos accelerates and continues in an in vitro culture system. This situation, in turn, implied that post-implantation mouse embryos might have some potential to regulate their own growth and size as seen by using an in vitro culture system without uterus factors. In conclusion, our results indicated that embryos have some ways in which to regulate their own size in mouse early development.
Echocardiography of transposition of the great arteries
Authors: Mahle William T. , Gonzalez Javier H. , Kreeger Joseph , Marx Gerald , Duldani Gul , Silverman Norman H.
Published: January 2013

The successful diagnosis, surgical planning, and long-term care of children with transposition of the great arteries require high-quality cardiac imaging with echocardiography. Echocardiography must identify the relevant anatomic variants of transposition of the great arteries, such as of ventricular septal defects and aortic arch anomalies. Methodical and detailed imaging of the coronary arteries is particularly important, as translocation of the coronary arteries is a critical component of the arterial switch procedure. Familiarity with the potential coronary artery variants and the ideal imaging planes is essential for an echocardiographer. Knowledge of both the early and late complications following the arterial switch procedure is essential to optimise post-operative echocardiography. These complications can include residual lesions leading to haemodynamic compromise or progressive late phenomena, such as aortic root dilatation and aortic insufficiency. Echocardiography will continue to be the cornerstone to the lifelong management of transposition of the great arteries, and improvements in technology and increased familiarity with modalities such as stress echocardiography will enhance the role of advanced imaging even further.
Ethical considerations for post-cardiotomy extracorporeal membrane oxygenation
Authors: Mavroudis Constantine , Mavroudis Constantine D. , Green Jeanette , Sade Robert M. , Jacobs Jeffrey P. , Kodish Eric
Published: January 2013

Significant advances have been made in extracorporeal life support, which has resulted in the increased use of post-cardiotomy extracorporeal membrane oxygenation. Retrospective studies have contributed to the ongoing evolution of selection criteria for post-cardiotomy extracorporeal membrane oxygenation. Current indications include failure to wean from cardiopulmonary bypass, haemodynamic collapse, pulmonary hypertension, post-repair of hypoplastic left heart syndrome, or need for bridge to transplantation. Short- and mid-term results are improving. Ethical concerns still attend the process, however. Moral risks related to post-cardiotomy extracorporeal membrane oxygenation may be encountered before, during, and after the open heart procedure. At each stage of the decision-making process, moral risks are encountered by many factors that may result in decisions that may be contrary to the best interests of the patient, parents, or use of shared societal resources. These moral risks centre around the selection process, informed consent, decision making in the operating room, and post-operative maintenance of extracorporeal membrane oxygenation. Consideration of such risks is affected by questions of haemodynamic stability, haematologic compromise, neurologic status, and family concerns. We conclude that thorough understanding of the relevant scientific literature, heightened awareness of moral risks, and incorporation of ethical tenets in clinical deliberation will guide the clinician to do the right thing.
Complexity stratification of the arterial switch operation: a second learning curve
Authors: Lacour-Gayet Francois
Published: January 2013

The arterial switch operation has become a safe operation in many centres. The complexity of the procedure has evolved over the last two decades. Several anatomical features can hardly be considered complex today, namely, normal coronary anatomy, circumflex coming off the right coronary artery, eccentric ostium, and early take-off of an infundibular artery. In addition, as peri-operative mortality becomes very low, the outcomes need to be evaluated on the peri-operative morbidity, late reoperations, and late deaths. The arterial switch operation remains complex in around 20% of the cases, where one or several complexity factors are associated. The complexity of the coronary arteries is a major factor. According to a classification essentially based on the course of the coronary arteries, complex coronaries include: double-looping coronaries, anterior-looping coronaries, intramural coronaries, and single coronary ostium. The most challenging coronary pattern remains the association of a single ostium with intramural course. Other features are equally complex: severe malalignment of the commissures, aortic arch obstruction, multiple ventricular septal defect, Taussig–Bing with subaortic obstruction, double-outlet right ventricle non-committed ventricular septal defect, transposition of the great arteries-intact ventricular septum >3 weeks, transposition of the great arteries-ventricular septal defect with high lung resistances and weight <2.5 kg. Owing to the fact that the risks of arterial switch operation vary according to the experience of the centres, we defined the arterial switch operation complexity based on a subjective approach as proposed by the Aristotle comprehensive score. The recent introduction of a morbidity score will allow to stratify more accurately the outcomes when the peri-operative mortality is very low or nil. The complexity of the coronary patterns tends to be well controlled today. It remains that rare coronary failures and aortic root dilation will occur in the long term, requiring a close follow-up of the most complex patients. Successfully achieving complex arterial switch operation implies a second learning curve.
Arrhythmia management in patients with a common arterial trunk and d-transposition of the great arteries
Authors: Decker Jamie A. , McCormack Jorge , Cohen Mitchell I.
Published: January 2013

Arrhythmias in patients with congenital heart disease present a challenge to the care of these patients and can result in significant morbidity and mortality. Transposition of the great arteries and common arterial trunk are no exceptions. It is important to identify risk factors for arrhythmia development in the peri-operative period. The peri-operative arrhythmia burden may relate to the underlying congenital heart disease, haemodynamic perturbations, operative events, and potential residual lesions. In addition, these patients are at risk for developing arrhythmias later in life, and non-invasive and potentially invasive arrhythmia surveillance should be a routine part of the care of these patients. This article highlights important strategies to manage arrhythmia development and prevention in this patient population.
Primary care management of patients with common arterial trunk and transposition of the great arteries
Authors: Boris Jeffrey R.
Published: January 2013

Primary care cardiology, also known as ambulatory or outpatient cardiology, for the longitudinal management of patients with common arterial trunk or with transposition of the great arteries is both poorly described and has limited evidence to justify its basis. This article discusses some of the various complications that these patients can develop, reviews the medical literature, and describes a framework for care of these complex patients from infancy to transition to adult congenital cardiac specialist care.
Rationalising the nomenclature of common arterial trunk
Authors: Jacobs Marshall L. , Anderson Robert H.
Published: January 2013

Hearts having a common arterial trunk belong to a family of congenital cardiac malformations for which traditional systems of classification and nomenclature are plagued by internal paradoxes, incompatibility between systems due to the lack of potential for identification of synonyms, or irreconcilable inconsistencies with our current knowledge of cardiac development and morphology. A simplified categorisation that classifies these hearts on the basis of pulmonary or aortic dominance reconciles the existing disparate categorisations, is in keeping with recent findings concerning cardiac development, and emphasises the principal morphologic determinant of surgical outcome.
Risk factors of recurrence and complication in radiofrequency catheter ablation of atrioventricular reentrant tachycardia in children and adolescents
Authors: Chen Tien H. , Tsai Ming-Lung , Chang Po-Cheng , Wo Hung-Ta , Chou Chung-Chuan , Wen Ming-Shien , Wang Chun-Chieh , Yeh San-Jou , Wu Delon
Published: January 2013

Background

To compare potential risk factors for complications and recurrence after radiofrequency catheter ablation in symptomatic atrioventricular reentrant tachycardia in children and adolescents.

Methods

We retrospectively reviewed the data of 213 consecutive patients with symptomatic atrioventricular reentrant tachycardia who underwent both electrophysiological study and radiofrequency catheter ablation, divided these patients into two groups, children (age <12 years) and adolescents (12 ≤ age < 18 years), and compared the location of the accessory pathway, success rate, recurrence rate, complications, presence of congenital heart disease, presence of intermittent ventricular pre-excitation, and presence of Wolff–Parkinson–White syndrome in the two groups.

Results

The position of the accessory pathway was mostly right sided in children (61.3%) and left sided in adolescents (61.5%). Children had significantly more congenital heart disease than adolescents (6.4% versus 0.8%). Univariate analysis showed children or adolescents with right-sided accessory pathways to be 6.84 times and those with accessory pathways on both sides of the septum 25 times more likely to relapse than those with a single accessory pathway. Multivariate analysis indicated that children or adolescents with two accessory pathways were six times, and those with intermittent ventricular pre-excitation nine times more at risk of relapsing following radiofrequency ablation than those with single accessory pathways. All five complications occurred in children.

Conclusions

The findings suggest that the position and number of accessory pathways and presence of intermittent ventricular pre-excitation are related to risks of recurrence of atrioventricular reentrant tachycardia in children and adolescents.
Surgical pulmonary valve insertion – when, how, and why
Authors: Lee Cheul , Jacobs Jeffrey P. , Lee Chang-Ha , Kwak Jae Gun , Chai Paul J. , Quintessenza James A.
Published: January 2013

Relief of right ventricular outflow tract obstruction in tetralogy of Fallot or similar physiology often results in pulmonary regurgitation. The resultant chronic volume overload can lead to right ventricular dilatation, biventricular dysfunction, heart failure symptoms, arrhythmias, and sudden death. Although pulmonary valve replacement can lead to improvement in functional class and a substantial decrease or normalisation of right ventricular volumes, the optimal timing of pulmonary valve replacement is not well defined. Benefits of pulmonary valve replacement have to be weighed against the risks of this procedure, including subsequent reoperation. This article will review the benefits and risks of pulmonary valve replacement, options for pulmonary valve substitute, and timing of pulmonary valve replacement in patients with chronic pulmonary regurgitation after relief of right ventricular outflow tract obstruction.
Intensive care management of neonates with d-transposition of the great arteries and common arterial trunk
Authors: Shamszad Pirouz , Moore Ryan A. , Ghanayem Nancy , Cooper David S.
Published: January 2013

Although mortality rates for patients with d-transposition of the great arteries remain quite low, these patients have a unique circulation that requires careful management in the peri-operative period. Despite the improved mortality for patients with common arterial trunk, the course in the intensive care unit is remarkable for significant morbidity and utilisation of significant resources. Pre-operative patient management focuses on balancing competing circulations, pulmonary and systemic, which exist in parallel rather than in series, as in the normal circulation. Post-operative patient management in both lesions focuses on optimising systemic output, respiratory status, and mitigating the effects of cardiopulmonary bypass. In this article, we review pre- and post-operative intensive care management in neonates with d-transposition of the great arteries and common arterial trunk.