bluuebunny/crossref_metadata_2025 huggingface dataset:
A NOVEL TYPE OF OPTICAL OSCILLATOR BASED ON A LIQUID CRYSTAL GAIN MEDIUM
Authors: RESIDORI STEFANIA , BORTOLOZZO UMBERTO , MONTINA ALBERTO , ARECCHI FORTUNATO TITO , HUIGNARD JEAN-PIERRE
Published: October 2007

A nonlinear optical medium results by the collective orientation of liquid crystal molecules tightly coupled to a transparent photoconductive layer made of a thin photorefractive BSO crystal. For this new kind of liquid crystal light-valve, we have recently demonstrated signal beam amplification and self-pumped phase conjugation. After giving a description of the device and its properties, we show here that the liquid crystal light-valve, when inserted in a ring optical cavity, has a gain large enough to overcome the losses, thus resulting in unidirectional field oscillation. The wide transverse size and the high nonlinearity of the liquid crystal medium allow us to explore dynamical regimes where a huge number of longitudinal and transverse modes are simultaneously amplified in the cavity. Up to date, such regimes have remained inaccessible for all the known types of optical cavities. In particular, we report the observation of high amplitude spatiotemporal pulses appearing in random space points and confined along the three space directions. Then, we present a theoretical model that takes into account the longitudinal dependence of the field in the liquid crystal optical oscillator, and show that spatiotemporal pulses confined in 3D space directions arise from the random superposition of many longitudinal and transverse modes oscillating at different frequencies.
SYNTHESIS, CRYSTAL STRUCTURE, SPECTROSCOPIC STUDIES ANDAB-INITIOCALCULATIONS ON THIRD-ORDER OPTICAL NONLINEARITY OF A FIVE-COORDINATE CHLOROIRON(III) COMPLEX
Authors: KARAKAS ASLI , DONMEZ EMINE , KARA HULYA , ELMALI AYHAN
Published: October 2007

A five-coordinate chloroiron(III) complex has been synthesized and characterized by X-ray diffraction analysis and UV-Vis spectroscopy. The maximum one-photon absorption (OPA) wavelengths recorded by both linear optical measurements and quantum mechanical computations using the configuration interaction (CI) method are estimated to be shorter than 400 nm in the UV region, showing good optical transparency to visible light. To investigate the microscopic third-order nonlinear optical (NLO) behavior of the title compound, we have computed both dispersion-free (static) and also frequency-dependent (dynamic) linear polarizabilities (α) and second hyperpolarizabilities (γ) at λ = 825–1125 nm and 1050–1600 nm wavelength areas using the time-dependent Hartree–Fock (TDHF) method. The ab-initio calculation results with non-zero values on (hyper)polarizabilities indicate that the synthesized molecule might possess microscopic third-order NLO phenomena.
DISSIPATIVE SELF-CONFINED OPTICAL BEAMS IN DOPED NEMATIC LIQUID CRYSTALS
Authors: ALBERUCCI ALESSANDRO , ASSANTO GAETANO
Published: October 2007

We study light localization in nonlinear non-local nematic liquid crystals capable of optical gain. We address the role of optical amplification on nonlinear beam propagation, considering various forms of gain and configurations.
LOCAL-FIELD AND MULTIPOLAR EFFECTS IN THE SECOND-HARMONIC RESPONSE OF ARRAYS OF METAL NANOPARTICLES
Authors: CANFIELD BRIAN K. , KUJALA SAMI , HUSU HANNU , KAURANEN MARTTI , BAI BENFENG , LAUKKANEN JANNE , KUITTINEN MARKKU , SVIRKO YURI , TURUNEN JARI
Published: October 2007

The distribution details of strongly-localized fields in metal nanostructures are important for strong interaction with the locally-varying non-linearity. Using gold nanodimers with nanogaps, we demonstrate that field localization alone is insufficient to drive a strong second-order response. Instead, polarization conversion of the local fundamental field combines with its asymmetric distribution along the dimer perimeter to yield strong responses. Strongly-localized fields may also favor higher-multipole (magnetic-dipole and electric-quadrupole) contributions to their nonlinear response. We show that the polarization-dependent interference of multipole sources in second-harmonic generation from gold nanoparticles allows the separation of their relative contributions.
ON A NEW CLASS OF LOAD BALANCING NETWORK PROTOCOLS
Authors: EIDENBENZ S. , HANSSON A. Å , RAMASWAMY V. , REIDYS C. M.
Published: October 2007

In this paper we study a new class of generic, parametrized, locally load-sensing (LLS) network-routing protocols over simple graphs, Y. These protocols are Y-"local" in the sense that they transmit packets only between Y-adjacent vertices and LLS since they base their "routing decisions" dynamically on queue-sizes of their neighbors and their relative distance to the destination. In the system each vertex has specific data-queues indexed by its respective Y-neighbors. The state of a vertex then consists of the collection of queue-sizes. The data-transmission protocols are formally specified in the framework of sequential dynamical systems, which allows us to categorize and classify our experiments. We will investigate the following scenario: for fixed Y we assume a single source/destination pair to be given and a system-update then consists of the collection of local protocol updates according to some fixed permutation of the Y-vertices. We then iterate the system-updates and thereby obtain the time evolution of the queue-sizes of the vertices. We will present and discuss results on the evolution of the load, i.e. the total number of packets in the network, the throughput, i.e. the rate at which packets arrive at the destination, and study the dependence of the queue-size dynamics on various other system parameters. In particular, we will analyze update schedule dependency and the impact of queue-capacity on system stability. We will show that our protocols can adapt and dynamically utilize new routes in a fixed network.
SCALE-INVARIANCE OF NORMALIZED YEARLY MEAN GRAIN YIELD ANOMALY SERIES
Authors: VALDEZ-CEPEDA RICARDO DAVID , DELGADILLO-RUIZ OLIVIA , MAGALLANES-QUINTANAR RAFAEL , MIRAMONTES-de LEÓN GERARDO , GARCÍA-HERNÁNDEZ JOSÉ LUIS , ENCISO-MUÑOZ AGUSTÍN , MENDOZA BLANCA
Published: October 2007

In crop science, tools of non-linear dynamics, fractals, chaos, intermittency and self-organized criticality may be employed and applied to the analysis of spatial variability and temporal behavior of agro-meteorological variables, soil properties, plant attributes, commercial yields, and prices of the agricultural products in order to gain knowledge about underlying complex processes. A search on the occurrence of particular scaling laws in Mexico's normalized yearly mean grain yield anomaly series of maize (Zea mays L.), beans (Phaseolus vulgaris L.), wheat (Triticum aestivum L.) and rice (Oriza sativa L.), using a variography approach is reported in this work. Additionally, power spectrum determination, time-frequency analysis, and estimation of Lyapunov exponent were performed for each profile in order to obtain useful information on the frequency contents and signs at which important frequencies occur as well as to determine their sensitivity to initial conditions. Fractal analysis gives us the order maize < wheat < rice < beans of sensitivity to external forcings, which was the same as that obtained through the Lyapunov exponent values. Results confirm that the final outputs (crop yields) in agricultural systems are affected by the magnetic and sunspot cycles of the Sun, the El Niño Southern Oscillation (ENSO), and the quasi-biannual oscillation, and possibly by the so-called heliospheric mid-term-quasi-periodicities, which act on different time (or spatial and spatial-time) scales. In particular, the maize normalized year anomaly series is clearly correlated with March, April, May and June series of the ENSO index.
AN INVESTIGATION OF MERGING AND COLLAPSING OF SOFTWARE NETWORKS
Authors: JENKINS S. , KIRK S. R.
Published: October 2007

We explore the use of complex networks for understanding of the interaction of computer software applications written in the Java object-oriented language with the "library classes" that they use (those provided by the Java Runtime Environment) as, essentially, a merged network of classes. The dependence of the software on the library is quantified using a recently introduced model that identifies phases close to a second-order phase transition existing in scale-free networks. An example is given of a piece of software whose class network collapses without the presence of the library classes, providing validation of a novel structural coupling measure; R coupling . The structural properties of the merged software-Java class networks were found to correlate with the proportion of Java classes contained within the subset delimited by R coupling . A mechanism for the preservation of the software class network is also provided for the cases studied where the removal of the library classes does not cause collapse.
GLOBAL STABILITY OF A NONLINEAR DISCRETE POPULATION MODEL WITH TIME DELAYS
Authors: FANG NA , CHEN XIAOXING
Published: October 2007

The global stability of a nonlinear discrete population model of Volterra type is studied. The model incorporates time delays. By linearization of the model at positive solutions and construction of Liapunov functionals, sufficient conditions are obtained to ensure that a positive solution of the model is stable and attracts all positive solutions. An example shows the feasibility of our main results.
Rediscovering and conserving the Lower Palaeozoic ‘treasures’ of Ethel Woods (neé Skeat) and Margaret Crosfield in northeast Wales
Authors: Burek C. V. , Malpas J. A.
Published: October 2007

This paper explores, within a historical context, the importance of geoconservation of not only sites but also artefacts, collections and specimens as well as letters and original documents. It sets out the search and finding of sites in northeast Wales and materials thought lost then found and the subsequent nomination of Regionally Important Geological/Geomorphological Sites (RIGS) conservation status of the sites to safeguard them for the future. It is important to note that RIGS can be designated for their historical value alone, which is in contrast to Sites of Special Scientific Interest (SSSIs), which are protected solely for their national scientific and research value.

The role of Ethel Woods (neé Skeat) and Margaret Crosfield in developing an understanding of the geological history of northeast Wales had been lost over time. This paper contains biographical sketches of the two women, followed by their Lower Palaeozoic lithological, structural and graptolite research and places it in an historical context. This case study illustrates how female curiosity, perseverance and attention to detail unearthed previously forgotten treasures.

The importance of conserving their sites, specimens and sketch field notebooks in our electronic and throw-away age is vital. The role of the North East Wales Regionally Important Geological/Geomorphological Sites (NEWRIGS) in conserving this information is put forward as an example of good practice.
Etheldred Benett (1776–1845): the first woman geologist?
Authors: Laming S. , Laming D.
Published: October 2007

Etheldred Benett was chosen as the emblem for the Conference ‘The role of women in the history of Geology’ held in November 2005 at the Geological Society of London. This short synopsis was submitted as a poster to the conference.
Grace Anne Milne (Lady Prestwich): more than an amanuensis?
Authors: Mather J. D. , Campbell I.
Published: October 2007

Grace Anne Milne, born in 1832, was the eldest child of James Milne of Findhorn in Morayshire and his wife Louisa Falconer, sister of the eminent botanist and palaeontologist Hugh Falconer. A marriage to George McCall in 1854 was short-lived. Widowed within 18 months and also losing her infant son, bereavement was followed by some years of depression. At this stage in her life an interest in geology was kindled by her uncle, who had been forced to give up his post in India because of the state of his health. From 1858 she travelled abroad with Falconer and subsequently resided with him in London until his death in 1865. During this period Grace both organized his household and acted as his secretary and companion. His regular and frank letters to her, about his scientific ideas, demonstrate that the relationship was more than one of domestic convenience. In 1870 Grace married Joseph Prestwich, a friend of Falconer and a London wine merchant who spent all his spare time ‘geologizing’. They lived at Shoreham near Sevenoaks in Kent and, between 1874 and 1887, lived for part of the year in Oxford after Prestwich's appointment as professor of geology at the university. With Prestwich's encouragement, from 1874, she began to publish novels, travel articles and scientific papers, as well as helping him in the preparation of his own lectures and diagrams. Her six
Chapters on Geology
were published in 1880 as well as other articles on subjects such as Scottish scenery and the Channel Tunnel. Most were published in magazines, such as
Leisure Hour
and
Every Girl's Magazine
, designed for a readership from the prosperous middle classes. Her interest in geology meant that she was able to play a full part in Prestwich's life, helping him with his work and travelling with him on his geological adventures. She was a geologist in her own right and held in high regard by the Fellows of the Geological Society.
Anne Phillips: John Phillips's geological companion
Authors: Morgan N.
Published: October 2007

In the late summer of 1842, Anne Phillips, working under her brother's instructions, found the crucial piece of evidence – known thereafter as Miss Phillips' conglomerate – that disproved Murchison's theories about the intrusive origin of the Malvern Hills. Later she travelled with her brother to examine the volcanics of the Auvergne. But these were not her first, or her only, geological achievements. From 1829 until her death in 1862, Anne served as housekeeper to her bachelor older brother. Orphaned at an early age, both John and Anne were taken in by their uncle, William Smith. Smith arranged for John's schooling and introduced John to the science of geology as a teenager. However, little evidence exists about Anne's upbringing and education. A series of 234 letters written by John to Anne between 1829 and 1841, and preserved in the Phillips archive at the Oxford University Museum of Natural History, reveals that Anne was clearly well educated and provided her brother with valuable scientific back-up as well as essential domestic and emotional support during their 33 years together.
Keeping it in the family: the extraordinary case of Cuvier's daughters
Authors: Orr M.
Published: October 2007

In the history of French geology, Georges Cuvier (1769–1832) is largely figured as the antagonist to Etienne Geoffroy St Hilaire, and as the arch-conservative who blocked the path of more ‘Darwinian’ ideas about the evolution of species. If historians mention him as a key player in Catholic French secondary education reform, despite being a Protestant, it is his extraordinarily enlightened encouragement and employment of his daughter, and perhaps even more importantly his step-daughter, in his collaborative projects which this paper investigates. Trained up in the latest scientific ideas of the epoch (because Cuvier lived with his family at the Jardin des Plantes), and as his ‘research assistants’, theirs is a story within women's history of science that has never been told. While to label them ‘women scientists’ or ‘geologists’ is a misnomer for the period in France, the direct contributions of these daughters to cross-Channel, geological endeavour of the period can at last have a place in the history of geology.
The influential Muriel Arber: a personal reflection
Authors: Robinson E.
Published: October 2007

Muriel Agnes Arber (1913–2004) was a female geologist of our time. However, she drew her energies from traditional sources, her family and their contribution to academic science, and the Geologists' Association. She benefited from the town and gown life of Cambridge and the influence of frequent visits to Lyme Regis, where family and science were drawn together, and where she met people to whom she could relate. This paper explore-these aspects of her life from a personal point of view.
The role of women in geological higher education – Bedford College, London (Catherine Raisin) and Newnham College, Cambridge, UK
Authors: Burek C. V.
Published: October 2007

This paper explores the place of geology within science education and the part women have played in geological higher education through history. The context is set firstly by exploring the informal role women have played in education in general and secondly by examining in detail the positions they held after 1870, when female higher education was put on to a more formal footing. To illustrate this, the evolution of two female colleges of higher education, Bedford College, London, and Newnham College, Cambridge, both offering geological education within science, are evaluated within a wider educational context. Finally, the cases of Dr Catherine Raisin, who was based at Bedford College, and Dr Gertrude Elles, based at Newnham College as role models are highlighted within this wider framework. This is supported by examining the student experience offered at these institutions through the formal laboratory and lecture provision and also informally by societies, specifically the Sedgwick Club in Cambridge and the Natural History Society at Bedford College, which were both supported strongly by the aforementioned female role models. Some other key figures, both students and staff, are also examined and an analysis of student destinations from both institutions during the late 19th and early 20th centuries are tabulated. The place of women firstly within science education and then specifically within geological education forms the context of this paper. The conclusions develop a portrait of early geological role-model women.
The role of Annie Greenly in the elucidation of the geology of Anglesey
Authors: Williams T. P. T.
Published: October 2007

Annie Greenly (née Barnard) is the great woman standing behind Edward Greenly. During his 25 years of surveying and producing the two volumes of the
Memoir of Anglesey
, she played a crucial role producing the index among other things. Her interaction with Greenly, first in the Highlands of Scotland and then on the Island of Anglesey, is detailed in this paper. Greenly outlived his wife by many years but he always acknowledged the debt he owed her.
Fossil hunters, a cave explorer and a rock analyst: notes on some early women contributors to geology
Authors: Creese M. R. S.
Published: October 2007

The work and achievements of nine women contributors to 19th- and early 20th-century developments in the geological sciences are sketched. Two of these women – Gordon Cumming and Gray – were Scottish, two – Owen and Maury – were from the United States, Cleve von Euler and Sahlbom were Swedish, and three – Pavlova, Solomko and Tsvetaeva – were Russian. Of these nine, seven worked in palaeontology (then and later the branch of the field most often taken up by women), Owen made her name primarily as a speleologist and Sahlbom was a rock and mineral analyst. The sketches are offered as additional material for the ongoing effort to uncover and assess the role played by women in early work in the sciences.
The contribution of British women to Carboniferous palaeobotany during the first half of the 20th century
Authors: Fraser H. E. , Cleal C. J.
Published: October 2007

During the first half of the 20th century, over a third of British palaeobotanists working on Carboniferous plants were women; neither before nor after this period have women played such a prominent role in this field. Few of these women were able to develop significant careers within the subject. They nevertheless produced some of the most innovative work in the field, pioneering work in plant phylogeny, cuticle studies, biostratigraphy, morphological variation, and anatomical thin sectioning. Two factors were critical for allowing this work to develop: the support of a small number of male colleagues, notably F. W. Oliver, W. H. Lang and D. H. Scott; and the existence of colleges that specifically supported women's education, including Newnham College (Cambridge), and Bedford, Royal Holloway, Westfield and University Colleges (London).
The quiet workforce: the various roles of women in geological and natural history museums during the early to mid-1900s
Authors: Wyse Jackson Patrick N. , Spencer Jones Mary E.
Published: October 2007

When examining the work of women in geology during the 18th and 19th centuries, one can broadly, and perhaps crudely, divide those women with geological interests into two broad groups: firstly, the geological wife, sister, or daughter, and the museum assistant; and secondly the museum user, the academic and the museum research scientist. It was not until the close of the 19th century that women began to have a role, albeit minor, in museum education. Women typically were employed in the major national or university museums as preparators, illustrators or assistants, and this trend continued until the 1930s. These women received little academic credit for their research as it was frequently incorporated into the publications of the men for whom they worked. Adelaide Quisenberry worked for Ray Bassler at the Smithsonian Institution in Washington DC, while Edith Goodyear was employed as an assistant to Edmund Garwood at University College, London. Edith later published an important paper in 1924, co-authored with Garwood. From 1964, Veronica Burns, a women of a very modest character, spent 17 years at Trinity College, Dublin, where as curator she diligently amassed many important specimens (some of which were used by colleagues in publications) and published two papers in her own right. By the 1930s, women were being appointed to serious research positions in some museums – among the earliest such appointment was that of Helen Muir-Wood, a specialist in Upper Palaeozoic brachiopods to the staff of the British Museum (Natural History). Anna Birchall Hastings was also appointed by the same institution to work on Recent bryozoans, but upon her marriage was required to relinquish her post, even though she had married a museum palaeontologist; he remained in post while she became a volunteer.
The historical problems of travel for women undertaking geological fieldwork
Authors: Burek C. V. , Kölbl-Ebert M.
Published: October 2007

From unsuitable clothes to lack of chaperones, from sexual harassment to lack of proper funding, throughout history women geologists have encountered difficulties travelling to their field locations or working in the field, whether these locations were close by or abroad. From Etheldred Benett to the present day, problems were often sociological and political as well as logistical. Most early women geologists were able to avoid many difficulties because they were protected through working locally, where their high social standing was known and respected, or because they worked in a team with husband, father or brother. However, the problem developed virulence in the second half of the 19th century, when women started to appear as students and professionally trained geologists. The single travelling woman geologist had to face discriminating attitudes, ranging from pity to disregard and even to sexual harassment. Benevolent society also had its problems with these women, when, for example, professors needed their wives as chaperones to take women students on field trips.

While women geologists out in the field certainly had and have to face problems because of their gender, those problems have also been used as an argument against employment of female geologists out of paternalistic concern, i.e. a discriminating strategy which is possibly the most difficult to reject.

This paper explores the difficulties of women geologists undertaking fieldwork from the late 18th to the mid-20th century by looking at specific examples and deducing the social and logistic reasons behind these problems.
Redox-dependent coronary metabolic dilation
Authors: Saitoh Shu-ichi , Kiyooka Takahiko , Rocic Petra , Rogers Paul A. , Zhang Cuihua , Swafford Albert , Dick Gregory M. , Viswanathan Chandrasekar , Park Yoonjung , Chilian William M.
Published: October 2007

We have observed that hydrogen peroxide (H2O2), the dismutated product of superoxide, is a coronary metabolic dilator and couples myocardial oxygen consumption to coronary blood flow. Because the chemical activity of H2O2 favors its role as an oxidant, and thiol groups are susceptible to oxidation, we hypothesized that coronary metabolic dilation occurs via a redox mechanism involving thiol oxidation. To test this hypothesis, we studied the mechanisms of dilation of isolated coronary arterioles to metabolites released by metabolically active (paced at 400 min) isolated cardiac myocytes and directly compared these responses with authentic H2O2. Studies were performed under control conditions and using interventions designed to reduce oxidized thiols [0.1 μM dithiothreitol (DTT) and 10 mM N-acetyl-l-cysteine (NAC)]. Aliquots of the conditioned buffer from paced myocytes produced vasodilation of isolated arterioles (peak response, 71% ± 6% of maximal dilation), whereas H2O2 produced complete dilation (92% ± 7%). Dilation to either the conditioned buffer or to H2O2 was significantly reduced by the administration of either NAC or DTT. The location of the thiols oxidized by the conditioned buffer or of H2O2 was determined by the administration of the fluorochromes monochlorobimane (20 μM) or monobromotrimethylammoniobimane (20 μM), which covalently label the reduced total or extracellular-reduced thiols, respectively. H2O2 or the conditioned buffer predominately oxidized intracellular thiols since the fluorescent signal from monochlorobimane was reduced more than that of monobromotrimethylammoniobimane. To determine whether one of the intracellular targets of thiol oxidation that leads to dilation is the redox-sensitive kinase p38 mitogen-activated protein (MAP) kinase, we evaluated dilation following the administration of the p38 inhibitor SB-203580 (10 μM). The inhibition of p38 attenuated dilation to either H2O2 or to the conditioned buffer from stimulated myocytes by a similar degree, but SB-203580 did not attenuate dilation to nitroprusside. Western blot analysis for the activated form of p38 (phospho-p38) in the isolated aortae revealed robust activation of this enzyme by H2O2. Taken together, our results show that an active component of cardiac metabolic dilation, like that of H2O2, produces dilation by the oxidation of thiols, which are predominately intracellular and dependent activation on the p38 MAP kinase. Thus coronary metabolic dilation appears to be mediated by redox-dependent signals.
Region of slowed conduction acts as core for spiral wave reentry in cardiac cell monolayers
Authors: Lin Joyce W. , Garber Libet , Qi Yue Rosa , Chang Marvin G. , Cysyk Joshua , Tung Leslie
Published: October 2007

Pathophysiological heterogeneity in cardiac tissue is related to the occurrence of arrhythmias. Of importance are regions of slowed conduction, which have been implicated in the formation of conduction block and reentry. Experimentally, it has been a challenge to produce local heterogeneity in a manner that is both reversible and well controlled. Consequently, we developed a dual-zone superfusion chamber that can dynamically create a small (5 mm) central island of heterogeneity in cultured cardiac cell monolayers. Three different conditions were studied to explore the effect of regionally slowed conduction on wave propagation and reentry: depolarization by elevated extracellular potassium, sodium channel inhibition with lidocaine, and cell-cell decoupling with palmitoleic acid. Using optical mapping of transmembrane voltage, we found that the central region of slowed conduction always served as the core region around which a spiral wave formed and then revolved following a period of rapid pacing. Because of the localized slowing in the core region, we observed experimentally for the first time an S shape of the spiral wave front near its tip. These results indicate that a small region of slowed conduction can play a crucial role in the formation, anchoring, and modulation of reentrant spiral waves.
Effects of enoximone on peripheral and central chemoreflex responses in humans
Authors: Gujic Marko , Dreyfuss Céline , Argacha Jean-François , Beloka Sofia , Adamopoulos Dionysios , Xhaët Olivier , Pathak Atul , van de Borne Philippe
Published: October 2007

cAMP plays an important role in peripheral chemoreflex function in animals. We tested the hypothesis that the phosphodiesterase inhibitor and inotropic medication enoximone increases peripheral chemoreflex function in humans. In a single-blind, randomized, placebo-controlled crossover study of 15 men, we measured ventilatory, muscle sympathetic nerve activity, and hemodynamic responses to 5 min of isocapnic hypoxia, 5 min of hyperoxic hypercapnia, and 3 min of isometric handgrip exercise, separated by 1 wk, with enoximone and placebo administration. Enoximone increased cardiac output by 120 ± 3.7% from baseline ( P < 0.001); it also increased the ventilatory response to acute hypoxia [13.6 ± 1 vs. 11.2 ± 0.7 l/min at 5 min of hypoxia, P = 0.03 vs. placebo (by ANOVA)]. Despite a larger minute ventilation and a smaller decrease in O2 desaturation (83 ± 1 vs. 79 ± 2%, P = 0.003), the muscle sympathetic nerve response to hypoxia was similar between enoximone and placebo (123 ± 6 and 117 ± 6%, respectively, P = 0.28). In multivariate regression analyses, enoximone enhanced the ventilatory ( P < 0.001) and sympathetic responses to isocapnic hypoxia. Hyperoxic hypercapnia and isometric handgrip responses were not different between enoximone and placebo ( P = 0.13). Enoximone increases modestly the chemoreflex responses to isocapnic hypoxia. Moreover, this effect is specific for the peripheral chemoreflex, inasmuch as central chemoreflex and isometric handgrip responses were not altered by enoximone.
Expression of a Gi-coupled receptor in the heart causes impaired Ca2+handling, myofilament injury, and dilated cardiomyopathy
Authors: McCloskey Diana T. , Turcato Sally , Wang Guan-Ying , Turnbull Lynne , Zhu Bo-Qing , Bambino Thomas , Nguyen Anita P. , Lovett David H. , Nissenson Robert A. , Karliner Joel S. , Baker Anthony J.
Published: October 2007

Increased signaling by Gi-coupled receptors has been implicated in dilated cardiomyopathy. To investigate the mechanisms, we used transgenic mice that develop dilated cardiomyopathy after conditional expression of a cardiac-targeted Gi-coupled receptor (Ro1). Activation of Gisignaling by the Ro1 agonist spiradoline caused decreased cellular cAMP levels and bradycardia in Langendorff-perfused hearts. However, acute termination of Ro1 signaling with the antagonist nor-binaltorphimine did not reverse the Ro1-induced contractile dysfunction, indicating that Ro1 cardiomyopathy was not due to acute effects of receptor signaling. Early after initiation of Ro1 expression, there was a 40% reduction in the abundance of the sarcoplasmic reticulum Ca2+-ATPase ( P < 0.05); thereafter, there was progressive impairment of both Ca2+handling and force development assessed with ventricular trabeculae. Six weeks after initiation of Ro1 expression, systolic Ca2+concentration was reduced to 0.61 ± 0.08 vs. 0.91 ± 0.07 μM for control ( n = 6–8; P < 0.05), diastolic Ca2+concentration was elevated to 0.41 ± 0.07 vs. 0.23 ± 0.06 μM for control ( n = 6–8; P < 0.01), and the decline phase of the Ca2+transient (time from peak to 50% decline) was slowed to 0.25 ± 0.02 s vs. 0.13 ± 0.02 s for control ( n = 6–8; P < 0.01). Early after initiation of Ro1 expression, there was a ninefold elevation of matrix metalloproteinase-2 ( P < 0.01), which is known to cause myofilament injury. Consistent with this, 6 wk after initiation of Ro1 expression, Ca2+-saturated myofilament force in skinned trabeculae was reduced to 21 ± 2 vs. 38 ± 0.1 mN/mm2for controls ( n = 3; P < 0.01). Furthermore, electron micrographs revealed extensive myofilament damage. These findings may have implications for some forms of human heart failure in which increased activity of Gi-coupled receptors leads to impaired Ca2+handling and myofilament injury, contributing to impaired ventricular pump function and heart failure.
Localization and mobility of the delayed-rectifer K+channel Kv2.1 in adult cardiomyocytes
Authors: O'Connell Kristen M. S. , Whitesell Jennifer D. , Tamkun Michael M.
Published: October 2007

The delayed-rectifier voltage-gated K+channel (Kv) 2.1 underlies the cardiac slow K+current in the rodent heart and is particularly interesting in that both its function and localization are regulated by many stimuli in neuronal systems. However, standard immunolocalization approaches do not detect cardiac Kv2.1; therefore, little is known regarding its localization in the heart. In the present study, we used recombinant adenovirus to determine the subcellular localization and lateral mobility of green fluorescent protein (GFP)-Kv2.1 and yellow fluorescent protein-Kv1.4 in atrial and ventricular myocytes. In atrial myocytes, Kv2.1 formed large clusters on the cell surface similar to those observed in hippocampal neurons, whereas Kv1.4 was evenly distributed over both the peripheral sarcolemma and the transverse tubules. However, fluorescence recovery after photobleach (FRAP) experiments indicate that atrial Kv2.1 was immobile, whereas Kv1.4 was mobile (τ = 252 ± 42 s). In ventricular myocytes, Kv2.1 did not form clusters and was localized primarily in the transverse-axial tubules and sarcolemma. In contrast, Kv1.4 was found only in transverse tubules and sarcolemma. FRAP studies revealed that Kv2.1 has a higher mobility in ventricular myocytes (τ = 479 ± 178 s), although its mobility is slower than Kv1.4 (τ1= 18.9 ± 2.3 s; τ2= 305 ± 55 s). We also observed the movement of small, intracellular transport vesicles containing GFP-Kv2.1 within ventricular myocytes. These data are the first evidence of Kv2.1 localization in living myocytes and indicate that Kv2.1 may have distinct physiological roles in atrial and ventricular myocytes.
Oxidative stress attenuates NO-induced modulation of sympathetic neurotransmission in the mesenteric arterial bed of spontaneously hypertensive rats
Authors: Macarthur Heather , Westfall Thomas C. , Wilken Gerald H.
Published: October 2007

Current evidence suggests that hyperactivity of the sympathetic nervous system and endothelial dysfunction are important factors in the development and maintenance of hypertension. Under normal conditions the endothelial mediator nitric oxide (NO) negatively modulates the activity of the norepinephrine portion of sympathetic neurotransmission, thereby placing a “brake” on the vasoconstrictor ability of this transmitter. This property of NO is diminished in the isolated, perfused mesenteric arterial bed taken from the spontaneously hypertensive rat (SHR), resulting in greater nerve-stimulated norepinephrine and lower neuropeptide Y (NPY) overflow from this mesenteric preparation compared with that of the normotensive Wistar-Kyoto rat (WKY). We hypothesized that increased oxidative stress in the SHR contributes to the dysfunction in the NO modulation of sympathetic neurotransmission. Here we demonstrate that the antioxidant N-acetylcysteine reduced nerve-stimulated norepinephrine and increased NPY overflow in the mesenteric arterial bed taken from the SHR. Furthermore, this property of N-acetylcysteine was prevented by inhibiting nitric oxide synthase with Nω-nitro-l-arginine methyl ester, demonstrating that the effect of N-acetylcysteine was due to the preservation of NO from oxidation. Despite a reduction in norepinephrine overflow, the nerve-stimulated perfusion pressure response in the SHR mesenteric bed was not altered by the inclusion of N-acetylcysteine. Studies including the Y1 antagonist BIBO 3304 with N-acetylcysteine demonstrated that this preservation of the perfusion pressure response was due to elevated NPY overflow. These results demonstrate that the reduction in the bioavailability of NO as a result of elevated oxidative stress contributes to the increase in norepinephrine overflow from the SHR mesenteric sympathetic neuroeffector junction.
Oxidative stress and adenosine A1receptor activation differentially modulate subcellular cardiomyocyte MAPKs
Authors: Ballard-Croft Cherry , Locklar Adam C. , Keith Byron J. , Mentzer Robert M. , Lasley Robert D.
Published: October 2007

The mechanism by which distinct stimuli activate the same mitogen-activated protein kinases (MAPKs) is unclear. We examined compartmentalized MAPK signaling and altered redox state as possible mechanisms. Adult rat cardiomyocytes were exposed to the adenosine A1receptor agonist 2-chloro- N6-cyclopentyladenosine (CCPA; 500 nM) or H2O2(100 μM) for 15 min. Nuclear/myofilament, cytosolic, Triton-soluble membrane, and Triton-insoluble membrane fractions were generated. CCPA and H2O2activated p38 MAPK and p44/p42 ERKs in cytosolic fractions. In Triton-soluble membrane fractions, H2O2activated p38 MAPK and p42 ERK, whereas CCPA had no effect on MAPK activation in this fraction. The greatest difference between H2O2and CCPA was in the Triton-insoluble membrane fraction, where H2O2increased p38 and p42 activation and CCPA reduced MAPK activation. CCPA also increased protein phosphatase 2A activity in the Triton-insoluble membrane fraction, suggesting that the activation of this phosphatase may mediate CCPA effects in this fraction. The Triton-insoluble membrane fraction was enriched in the caveolae marker caveolin-3, and >85% of p38 MAPK and p42 ERK was bound to this scaffolding protein in these membranes, suggesting that caveolae may play a role in the divergence of MAPK signals from different stimuli. The antioxidant N-2-mercaptopropionyl glycine (300 μM) reduced H2O2-mediated MAPK activation but failed to attenuate CCPA-induced MAPK activation. H2O2but not CCPA increased reactive oxygen species (ROS). Thus the adenosine A1receptor and oxidative stress differentially modulate subcellular MAPKs, with the main site of divergence being the Triton-insoluble membrane fraction. However, the adenosine A1receptor-mediated MAPK activation does not involve ROS formation.
Role of angiotensin II in endothelial dysfunction induced by lipopolysaccharide in mice
Authors: Lund Donald D. , Brooks Robert M. , Faraci Frank M. , Heistad Donald D.
Published: October 2007

Endotoxin [or lipopolysaccharide (LPS)] increases levels of superoxide in blood vessels and impairs vasomotor function. Angiotensin II plays an important role in the generation of superoxide in several disease states, including hypertension and heart failure. The goal of this study was to determine whether the activation of the renin-angiotensin system contributes to oxidative stress and endothelial dysfunction after endotoxin. We examined the effects of enalapril (an angiotensin-converting enzyme inhibitor) or L-158809 (an angiotensin receptor blocker) on increases of superoxide and vasomotor dysfunction in mice treated with LPS. C57BL/6 mice were treated with either enalapril (60 mg·kg−1·day−1) or L-158809 (30 mg·kg−1·day−1) for 4 days. After the third day, LPS (10–20 mg/kg) or vehicle was injected intraperitoneally, and one day later, vasomotor function of the aorta was examined in vitro. After precontraction with PGF2α, the maximal responses to sodium nitroprusside were similar in the aorta from normal and LPS-treated mice. In contrast, the relaxation to acetylcholine was impaired after LPS (54 ± 5% at 10−5, mean ± SE) compared with vessels treated with vehicle (88 ± 1%; P < 0.05). Enalapril improved ( P < 0.05) relaxation in response to acetylcholine to 81 ± 6% after LPS. L-158809 also improved relaxation in response to acetylcholine to 77 ± 4% after LPS. Superoxide (measured with lucigenin and hydroethidine) was increased ( P < 0.05) in aorta after LPS, and levels were reduced ( P < 0.05) following enalapril and L-158809. Thus, after LPS, enalapril and L-158809 reduce superoxide levels and improve relaxation to acetylcholine in the aorta. The findings suggest that activation of the renin-angiotensin system contributes importantly to oxidative stress and endothelial dysfunction after endotoxin.
Liver Transplantation for Hepatocellular Carcinoma beyond the Milan Criteria: The Controversies Continue
Authors: Lee Hyo-Suk
Published: October 2007

Liver transplantation has now become a favored option for patients with early-stage hepatocellular carcinoma (HCC) with or without impaired hepatic function as a complication of underlying cirrhosis. To overcome the persistent donor organ shortage, the use of adult-to-adult living donor liver transplantation (LDLT) has recently increased, especially in Asian countries. In the use of LDLT, several controversies remain including the safety of living donation and expanding the current Milan criteria. Most physicians agree that criteria for transplanting patients with HCC should be expanded beyond the Milan criteria because the Milan criteria miss a number of patients who may benefit from LDLT; however, the expanded criteria proposed were different (the size and number of HCCs and the biologic markers) from one center to the other. When we consider LDLT as a treatment option for patients with HCC, donor safety should be kept in mind first, and the wishes of both patient and donor should be weighed against the potential (if small) risk for the donor. In contrast to deceased donor liver transplantation, the benefit of LDLT is better appreciated in terms of gain in life expectancy than in terms of survival when the wishes of both patient and donor outweigh the donor risk. Further research on the predictors of benefit of LDLT to HCC patients other than the size and number of HCC such as molecular profiling of HCC are necessary to finally reach a consensus.
Living Donor Liver Transplantation for Hepatocellular Carcinoma: Tokyo University Series
Authors: Sugawara Yasuhiko , Tamura Sumihito , Makuuchi Masatoshi
Published: October 2007

Background/Aims: Hepatocellular carcinoma (HCC) is one of the major indications for living donor liver transplantation (LDLT). Unlike in deceased donor liver transplantation, however, there exist no universally adopted selection criteria for the potential candidates with HCC in LDLT. Our institutional guideline for HCC in LDLT has been up to 5 nodules with a maximum diameter of 5 cm (5-5 rule). Methods: A total of 78 adult patients underwent adult living donor liver transplantation at University of Tokyo between April 1996 and October 2005. Results: Overall and recurrence-free survival at 5 years after transplantation were 75 and 90%, respectively, with a median follow-up of 2 years. When stratified by the 5-5 rule, recurrence-free survival at 3 years for patients fulfilling the criteria and those exceeding the criteria was 94 and 50%, respectively. Conclusions: In LDLT, the indication for HCC might be expanded from the Milan criteria, with equivalent outcomes. Further study, however, is necessary to justify the general application of the 5-5 rule.
HCC in Living Donor Liver Transplantation: Can We Expand the Milan Criteria?
Authors: Kwon Choon Hyuck David , Kim Doo Jin , Han Young Seok , Park Jae Berm , Choi Gyu Seong , Kim Sung Joo , Joh Jae Won , Lee Suk-Koo
Published: October 2007

Background: The tumor biology of hepatocellular carcinoma (HCC) affects recurrence after liver transplantation (LT), but most selection guidelines are based only on tumor size and number. The aim of the study is to evaluate the possibility of expanding the selection criteria in living donor LT (LDLT) without compromising patient survival by adding α-fetoprotein (AFP) in selection guideline. Methods: One hundred thirty-nine patients who received LDLT with the diagnosis of HCC and survived more than 3 months were enrolled. The operability was based on Milan criteria but LT beyond the criteria was performed when requested by the patients and/or the guardian after thorough explanation. Results: The median follow-up duration was 28 months. One-, three- and five-year survival rates were 92.2, 82.6, and 79.9%. There was no survival difference between patients within or beyond Milan (p = 0.76). Serum AFP level >400 ng/ml, tumor size >5 cm, and vascular invasion were significant on univariate analysis, but only vascular invasion was significant on multivariate analysis (p = 0.007). Patients with >3 tumor nodules had better survival compared to ≤3 nodules (p = 0.196). Patient selection using tumor size ≤5 cm and AFP ≤400 ng/ml without limitation of tumor numbers could expand patient selection and improve patient survival. Conclusion: Application of serum AFP level to selection of HCC for LT affords better patient selection criteria.
Liver Transplantation for Hepatocellular Carcinoma in Patients Who Do Not Meet the Milan Criteria
Authors: Suh Kyung-Suk , Cho Eung-Ho , Lee Hae Won , Shin Woo Young , Yi Nam-Joon , Lee Kuhn Uk
Published: October 2007

Background: To expand the Milan criteria, prognostic factors other than size and number of tumor may be necessary. We analyzed outcome and prognostic factors in patients with hepatocellular carcinoma (HCC) exceeding Milan criteria to select favorable group of patients. Methods: Between November 1997 and December 2005, 104 cases of liver transplantation for patients with HCC were performed at our center. Twenty-four patients did not meet the Milan criteria preoperatively. Among these 24 patients, 19 had no major vascular invasion at the time of surgery. We analyzed the survival and prognostic factors of these 19 patients. The mean follow-up period was 33 months (range 6–89). Results: Three-year survival rate in 19 patients was 67.4%. Three-year survival rates were significantly higher when preoperative alpha-fetoprotein was less than 400 ng/ml (86.2 vs. 0%, p<0.001) when Edmonson-Steiner’s histological grade 1 or 2 (100 vs. 40%, p = 0.036) and when microvascular invasion was absent (78.6 vs. 30%, p = 0.039). Conclusion: If vascular invasion is absent in preoperative radiological studies, and the preoperative alpha-fetoprotein is less than 400 ng/ml, our findings suggest a good prognosis after liver transplantation for HCC patients who do not meet the Milan criteria.
Relation between Serum Thyroid Hormone and ‘Nondipper’ Circadian Blood Pressure Variability
Authors: Kanbay Mehmet , Turgut Faruk , Karakurt Feridun , Isik Bunyamin , Alkan Rabia , Akcay Ali , Yigitoglu Ramazan , Covic Adrian
Published: October 2007

Currently, the pathogenesis of nondipper hypertension remains largely unclear in patients without any renal or endocrine pathology. It is well known that overt hypothyroidism is strongly associated with diastolic hypertension. However, no study has addressed the pathogenic role of TSH, free T3 (FT3), and free T4 (FT4) in nondipper hypertension. The aim of the present investigation is to evaluate if higher TSH, low FT3 and FT4 would be associated with a nondipper hypertension profile, in patients with normal renal function and without any overt thyroid hormone disorder. 131 subjects were screened and those who met the following inclusion criteria were enrolled: (1) glomerular filtration rate (GFR) >60 ml/min; (2) no history of thyroid disorders; (3) no history of thyroid hormone medication. All subjects underwent 24-hour ambulatory blood pressure monitoring on a usual working day. Of the total population, 59 patients (45%) were classified as dippers and 72 (55%) were classified as nondippers. The only significant differences between dipper and nondipper patients appear to be related to FT3 levels and GFR. Nondipper patients had lower FT3 levels (4.5 ± 0.6 vs. 4.0 ± 0.9 pmol/l, p = 0.02) and low GFR (80.5 ± 12.2 vs. 86.9 ± 16.9 ml/min, p = 0.03), compared to dipper patients. The final regression model included serum TSH, FT3 levels, and GFR; the only independent predictor of nondipper hypertension was FT3 (p = 0.04). In conclusion, even if the mechanisms of our findings remain incompletely understood, we demonstrate a graded independent relation between lower level of FT3 and the risk of nondipping. Further studies are warranted to confirm this relationship and to elucidate the pathogenetic mechanisms of this relationship.