bluuebunny/crossref_metadata_2025 huggingface dataset:
Les cartilages calcifiés de la petite roussette (Scyliorhinus canicula L., Chondrichthyens): histologie et ultrastructure
Authors: Bordat C.
Published: August 2008

The ultrastructure of the mandibular tesserae and of the calcifications of the double cone in the vertebrae were studied in the lesser spotted dogfish, Scyliorhinus canicula. New evidence is provided that shows with certainty that chondrocytes degenerate in the tesserae. Ultrastructural study of the collagen substrate in the tesserae also suggested new concepts on collagen organization in the tesserae: very thick collagen fibers have a radial arrangement in the superficial portion of each tessera and evidence also points to the probable noncollagenic nature of the substrate of the Liesegang rings. Observation of early tesseral stages strongly suggests that these formations have a dual origin, which might explain the different configurations of the tesserae: globular on the inner surface and parallel to the collagen fibers on the external surface. The presence or absence of bone in the tesserae will have to be examined anew since this study seems to indicate that the tesserae are entirely cartilaginous in this dogfish. Examination of serial sections of the axial skeleton has shown that the complex structures of the skeleton have very different aspects at different sectional levels in the vertebra. However, at all sectional levels, the double calcified cone seems to be composed of a calcified fibrous cartilage in which chondrocytes degenerate. Our observations on the tesserae and on the double cone clearly demonstrate the degenerative process of the chondrocytes in these structures. Our results also show that, in contrast to other species, this dogfish has no vascularization in any of its cartilages, calcified or not.[Journal translation]
Comparaison de critères utilisables pour l'étude de la structure des populations du polychète Nereis virens (Sars)
Authors: Desrosiers G. , Vincent B. , Retière C. , Boucher L.
Published: August 2008

The various biometrical criteria used in the study of the population structure of the annelid polychaete Nereis virens (Sars) are reviewed. This type of study, which requires the examination of large numbers of specimens representing all size classes, is sometimes complicated by the occurrence of autotomy, a phenomenon quite frequent in this species, and by mechanical breaks during sampling and sieving. Measurements such as total length, width of an anterior segment, and total weight are not good criteria. We have used a new biometrical criterium developed at the Laboratoire maritime de Dinard (France). This criterium is based on a partial weight of animals that have been put in formaldehyde and wiped; the weight is determined from an histogram in which breaking points are "ranked". This ponderal measurement has been compared with the linear measurement of the jaw length. The new method allows the manipulation of a larger number of individuals and it is easier and faster to use than the method based on jaw measurements.[Journal translation]
Food preference and relative influence of temperature and food quality on life history characteristics of a grazing mayfly, Ephemerella ignita (Poda)
Authors: Rosillon Dominique
Published: August 2008

In choice experiments, starved larvae of Ephemerella ignita (Poda) moved preferentially to compartments with a diatom-rich diet rather than to those with a detritus diet. Growth rate, mortality rate, larval developmental time, adult size, and fecundity of E. ignita were assessed in response to rearing on two diets (diatoms and detritus) at four constant temperatures (4.5 – 18 °C). On each diet, growth rate (range 0.30 – 6.2% length/d) increased with increasing temperature according to a power law (Y = axb). At any temperature, growth rate was significantly higher on the diatom diet than on the detritus diet. Mortality rate (range 0.2 – 6.5%/d) increased with increasing temperature and was higher on the detritus diet than on the diatom diet. Developmental time varied significantly with temperature for animals fed diatoms according to a hyperbolic relationship. The thermal requirement for completing larval growth from hatching to emergence on a diatom diet was estimated at about 950 degree-days above a threshold of 3.5 °C (range 9.5 – 18 °C). Very few larvae reared on detritus achieved the adult stage and their developmental time seemed longer. Subimago weight did not vary significantly with temperature, but fecundity (range 435 – 1320 eggs per female) was significantly lower at 9.5 °C than at 14.5 and 18 °C in larvae fed diatoms. Fecundity of females from larvae fed detritus was very low (range 5 – 150 eggs). The reproductive effort (number of eggs per milligram of subimago weight; range 66 – 125) followed a clear linear increasing relationship with temperature (9.5 to 18 °C) for animals reared on diatoms. Poor food quality could probably restrict distribution of E. ignita by reducing fecundity. In conclusion, these results show that the thermal equilibrium hypothesis must be extended to other environmental factors. They also support the hypothesis of a bivoltine cycle of E. ignita under favorable thermic and food conditions.
Seasonal changes in digestion in black bears
Authors: Brody Allan J. , Pelton Michael R.
Published: August 2008

The ability of bears (Ursus spp.) to accumulate fat reserves before winter denning is essential to winter survival and successful reproduction. We conducted an experiment to determine if the digestive ability of black bears (U. americanus) changes seasonally. Six captive bears were fed commercial dog food rations and the digestibilities of gross energy and crude protein were determined in August and again in November. Bears showed significantly higher digestion of gross energy and significantly lower digestion of crude protein in November than in August. We suggest that a systemically mediated increase in fat and carbohydrate assimilation, at the expense of protein assimilation, occurs in the fall, and that this is an adaptation facilitating rapid weight gain before denning.
Foregut innervation in juvenile Spirobranchus spinosus (Polychaeta)
Authors: Lacalli Thurston C. , West Jenifer E.
Published: August 2008

The intraepithelial system of nerves supplying the larval pharynx in trochophores of the serpulid polychaete Spirobranchus spinosus is retained through metamorphosis and, with minimal alteration, provides the sole source of nerves in the juvenile foregut. Stomatogastric nerves and ganglia in adult worms are typically subepithelial in position. Intraepithelial innervation of the type described is previously unreported from either juveniles or adults.
LOCALIZATION OF FERMIONIC FIELDS ON BRANEWORLDS WITH BULK TACHYON MATTER
Authors: ZHANG XIN-HUI , LIU YU-XIAO , DUAN YI-SHI
Published: August 2008

Recently, Pal and Skar in Ref. 33 proposed a mechanism to arise the warped braneworld models from bulk tachyon matter, which are endowed with a thin brane and a thick brane. In this framework, we investigate localization of fermionic fields on these branes. As in the 1/2-spin case, the field can be localized on both the thin and thick branes with inclusion of scalar background. In the 3/2-spin extension, the general supergravity action coupled to chiral supermultiplets is considered to produce the localization on both the branes as a result.
THE ELEMENTAL COMPOSITION OF HIGH-ENERGY COSMIC RAYS: MEASUREMENTS WITH TRACER
Authors: BOYLE P. J.
Published: August 2008

TRACER ("Transition Radiation Array for Cosmic Energetic Radiation") is a balloon borne instrument that has been developed to directly measure the composition and energy spectra of individual heavy elements up to 1015 eV particle-1. TRACER achieves a large geometric factor (5 m2 sr) through the use of a Transition Radiation Detector utilizing arrays of single wire proportional tubes. TRACER has measured the energy spectra of the elements O, Ne, Mg, Si, S, Ar, Ca and Fe . The energy spectra reach energies in excess of 1014 eV particle-1 and exhibit nearly the same spectral index (2.65±0.05) for all elements.
SCENARIOS FOR PRICE DETERMINATION IN INCOMPLETE MARKETS
Authors: XANTHOPOULOS S. Z. , YANNACOPOULOS A. N.
Published: August 2008

We study the problem of determination of asset prices in an incomplete market proposing three different but related scenarios, based on utility pricing. One scenario uses a market game approach whereas the other two are based on risk sharing or regret minimizing considerations. Dynamical schemes modeling the convergence of the buyer and seller prices to a unique price are proposed. The case of exponential utilities is treated in detail, in the simplest possible example of an incomplete market, the trinomial model.
MEASURING THE MARKET RISK OF FREIGHT RATES: A VALUE-AT-RISK APPROACH
Authors: ANGELIDIS TIMOTHEOS , SKIADOPOULOS GEORGE
Published: August 2008

The fluctuation of shipping freight rates (freight rate risk) is an important source of market risk for all participants in the freight markets including hedge funds, commodity and energy producers. We measure the freight rate risk by the Value-at-Risk (VaR) approach. A range of parametric and non-parametric VaR methods is applied to various popular freight markets for dry and wet cargoes. Backtesting is conducted in two stages by means of statistical tests and a subjective loss function that uses the Expected Shortfall, respectively. We find that the simplest non-parametric methods should be used to measure freight rate risk. In addition, freight rate risk is greater in the wet cargoes markets. The margins in the growing freight derivatives markets should be set accordingly.
A FAST, STABLE AND ACCURATE NUMERICAL METHOD FOR THE BLACK–SCHOLES EQUATION OF AMERICAN OPTIONS
Authors: EHRHARDT MATTHIAS , MICKENS RONALD E.
Published: August 2008

In this work we improve the algorithm of Han and Wu [SIAM J. Numer. Anal. 41 (2003), 2081–2095] for American Options with respect to stability, accuracy and order of computational effort. We derive an exact discrete artificial boundary condition (ABC) for the Crank–Nicolson scheme for solving the Black–Scholes equation for the valuation of American options. To ensure stability and to avoid any numerical reflections we derive the ABC on a purely discrete level.

Since the exact discrete ABC includes a convolution with respect to time with a weakly decaying kernel, its numerical evaluation becomes very costly for large-time simulations. As a remedy we construct approximate ABCs with a kernel having the form of a finite sum-of-exponentials, which can be evaluated in a very efficient recursion. We prove a simple stability criteria for the approximated artificial boundary conditions.

Finally, we illustrate the efficiency and accuracy of the proposed method on several benchmark examples and compare it to previously obtained discretized ABCs of Mayfield and Han and Wu.
DISCOUNT CURVE ESTIMATION BY MONOTONIZING MCCULLOCH SPLINES
Authors: DETTE HOLGER , ZIGGEL DANIEL
Published: August 2008

In this paper a new method for monotone estimation of discount curves is proposed. The main idea of this approach is a simple modification of the commonly used (unconstrained) McCulloch Spline. We construct an integrated density estimate from the predicted values of the discount curve. It can be shown that this statistic is an estimate of the inverse of the discount function and the final estimate can be obtained by a numerical inversion. The resulting procedure is simple and we have implemented it in Excel and VBA, respectively. The performance is illustrated by several examples, in which the curve was previously estimated with an unconstrained McCulloch Spline.
The Compilation of Math Pattern for Productivity in Educational Organisations, Service Organisations (Municipalities), and Industrial Organisations Based on Organisational Climate in Iran
Authors: Nazem Fattah
Published: August 2008

The purpose of the present study is to investigate the relationship between organisational climate with the productivity of managers' services in educational, service, and industrial organisations, in order to present a suitable management pattern. The population of the research consist of all managers who work in Tehran high schools, municipalities managers, and managers of the National Company Petro-Chemical Industries. Two hundred and forty five High School managers, 52 municipalities managers, and 349 managers of National Company of Petro-Chemical were selected. The research tools are the questionnaires of organisational climate (Litwin and Stringer, 1968) and productivity (Smith, et al., 1998). In this way that the questionnaires of organisational climate and the managers productivity were given to the staff. For each manager, three clerks were chosen to complete the questionnaires. The results of applying the analysis of multi-variation regression are as follows:

(A) There is a relationship between the organisational climate and the productivity of the managers' services.

(B) The math pattern for the productivity of the managers' services in educational, service (municipalities), and industrial organisations are as follows:

(1) Productivity = 0.64 × organisational climate + (-22.62).

(2) Productivity = 0.73 × organisational climate + (-15.825).

(3) Productivity = 0.65 × organisational climate + (-29.19).
Post-release reliability growth in software products
Authors: Jalote Pankaj , Murphy Brendan , Sharma Vibhu Saujanya
Published: August 2008

Most software reliability growth models work under the assumption that reliability of software grows due to the removal of bugs that cause failures. However, another phenomenon has often been observed—the failure rate of a software product following its release decreases with time even if no bugs are corrected. In this article we present a simple model to represent this phenomenon. We introduce the concept of initial transient failure rate of the product and assume that it decays with a factor α per unit time thereby increasing the product reliability with time. When the transient failure rate decays away, the product displays a steady state failure rate. We discuss how the parameters in this model—initial transient failure rate, decay factor, and steady state failure rate—can be determined from the failure and sales data of a product. We also describe how, using the model, we can determine the product stabilization time—a product quality metric that describes how long it takes a product to reach close to its stable failure rate. We provide many examples where this model has been applied to data from released products.
Topology analysis of software dependencies
Authors: Robillard Martin P.
Published: August 2008

Before performing a modification task, a developer usually has to investigate the source code of a system to understand how to carry out the task. Discovering the code relevant to a change task is costly because it is a human activity whose success depends on a large number of unpredictable factors, such as intuition and luck. Although studies have shown that effective developers tend to explore a program by following structural dependencies, no methodology is available to guide their navigation through the thousands of dependency paths found in a nontrivial program. We describe a technique to automatically propose and rank program elements that are potentially interesting to a developer investigating source code. Our technique is based on an analysis of the topology of structural dependencies in a program. It takes as input a set of program elements of interest to a developer and produces a fuzzy set describing other elements of potential interest. Empirical evaluation of our technique indicates that it can help developers quickly select program elements worthy of investigation while avoiding less interesting ones.
The impact of research on the development of middleware technology
Authors: Emmerich Wolfgang , Aoyama Mikio , Sventek Joe
Published: August 2008

The middleware market represents a sizable segment of the overall Information and Communication Technology market. In 2005, the annual middleware license revenue was reported by Gartner to be in the region of $8.5 billion. In this article we address the question whether research had any involvement in the creation of the technology that is being sold in this market? We attempt a scholarly discourse. We present the research method that we have applied to answer this question. We then present a brief introduction into the key middleware concepts that provide the foundation for this market. It would not be feasible to investigate any possible impact that research might have had. Instead we select a few very successful technologies that are representative for the middleware market as a whole and show the existence of impact of research results in the creation of these technologies. We investigate the origins of Web services middleware, distributed transaction processing middleware, message-oriented middleware, distributed object middleware and remote procedure call systems. For each of these technologies we are able to show ample influence of research and conclude that without the research conducted by PhD students and researchers in university computer science labs at Brown, CMU, Cambridge, Newcastle, MIT, Vrije, and University of Washington as well as research in industrial labs at APM, AT&T Bell Labs, DEC Systems Research, HP Labs, IBM Research, and Xerox PARC we would not have middleware technology in its current form. We summarise the article by distilling lessons that can be learnt from this evidenced impact for future technology transfer undertakings.
ACM's place in the global picture
Authors: Hall Wendy
Published: August 2008

ACM's new president intends to make international initiatives a top priority, hoping to share the Association's riches with a greater global audience.
Finding diamonds in the rough
Authors: Kroeker Kirk L.
Published: August 2008

Spectral graph theory has proven to be very useful for text search and retrieval and for refining predictive-analysis systems.
Ubiquitous video
Authors: Kugler Logan
Published: August 2008

Scalable and distributed video coding offers the promise of two-way, real-time video.
Wisdom from Randy Pausch
Authors: Hoffmann Leah
Published: August 2008

Randy Pausch, author of the best-selling
The Last Lecture
and a virtual-world innovator, on computer science, Alice, and teaching.
IT policyScience policy isn't always about science
Authors: Wilson Cameron , Harsha Peter
Published: August 2008

What is the appropriate role and level of influence for science and technical advice in policy deliberations?
How do I model state?
Authors: Foster Ian , Parastatidis Savas , Watson Paul , Mckeown Mark
Published: August 2008

A study of the technology and sociology of Web service specifications.
Powering down
Authors: Garrett Matthew
Published: August 2008

Smart power management is all about doing more with the resources we have.
Software engineering and formal methods
Authors: Hinchey Mike , Jackson Michael , Cousot Patrick , Cook Byron , Bowen Jonathan P. , Margaria Tiziana
Published: August 2008

The answer to software reliability concerns may lie in formal methods.
Design and code reviews in the age of the internet
Authors: Meyer Bertrand
Published: August 2008

New collaboration tools allow geographically distributed software-development teams to boost the venerable concept of code review.
Information integration in the enterprise
Authors: Bernstein Philip A. , Haas Laura M.
Published: August 2008

A guide to the tools and core technologies for merging information from disparate sources.
Improved algorithms for optimal embeddings
Authors: Chandran Nishanth , Moriarty Ryan , Ostrovsky Rafail , Pandey Omkant , Safari Mohammad Ali , Sahai Amit
Published: August 2008

In the last decade, the notion of metric embeddings with small distortion has received wide attention in the literature, with applications in combinatorial optimization, discrete mathematics, and bio-informatics. The notion of embedding is, given two metric spaces on the same number of points, to find a bijection that minimizes maximum Lipschitz and bi-Lipschitz constants. One reason for the popularity of the notion is that algorithms designed for one metric space can be applied to a different one, given an embedding with small distortion. The better distortion, the better the effectiveness of the original algorithm applied to a new metric space.

The goal recently studied by Kenyon et al. [2004] is to consider all possible embeddings between two
finite
metric spaces and to find the best possible one; that is, consider a single objective function over the space of all possible embeddings that minimizes the distortion. In this article we continue this important direction. In particular, using a theorem of Albert and Atkinson [2005], we are able to provide an algorithm to find the optimal bijection between two line metrics, provided that the optimal distortion is smaller than 13.602. This improves the previous bound of 3 + 2√2, solving an open question posed by Kenyon et al. [2004]. Further, we show an inherent limitation of algorithms using the “forbidden pattern” based dynamic programming approach, in that they cannot find optimal mapping if the optimal distortion is more than 7 + 4√3 (≃ 13.928). Thus, our results are almost optimal for this method. We also show that previous techniques for general embeddings apply to a (slightly) more general class of metrics.
Fault-tolerant facility location
Authors: Swamy Chaitanya , Shmoys David B.
Published: August 2008

We consider a fault-tolerant generalization of the classical uncapacitated facility location problem, where each client
j
has a requirement that
r

j

distinct
facilities serve it, instead of just one. We give a 2.076-approximation algorithm for this problem using LP rounding, which is currently the best-known performance guarantee. Our algorithm exploits primal and dual complementary slackness conditions and is based on
clustered randomized rounding
. A technical difficulty that we overcome is the presence of terms with negative coefficients in the dual objective function, which makes it difficult to bound the cost in terms of dual variables. For the case where all requirements are the same, we give a primal-dual 1.52-approximation algorithm.

We also consider a fault-tolerant version of the
k
-median problem. In the metric
k
-median problem, we are given
n
points in a metric space. We must select
k
of these to be centers, and then assign each input point
j
to the selected center that is closest to it. In the fault-tolerant version we want
j
to be assigned to
r

j

distinct centers. The goal is to select the
k
centers so as to minimize the sum of assignment costs. The primal-dual algorithm for fault-tolerant facility location with uniform requirements also yields a 4-approximation algorithm for the fault-tolerant
k
-median problem for this case. This the first constant-factor approximation algorithm for the uniform requirements case.
Atomic congestion games among coalitions
Authors: Fotakis Dimitris , Kontogiannis Spyros , Spirakis Paul
Published: August 2008

We consider algorithmic questions concerning the existence, tractability, and quality of Nash equilibria, in atomic congestion games among users participating in selfish coalitions.

We introduce a coalitional congestion model among atomic players and demonstrate many interesting similarities with the noncooperative case. For example, there exists a potential function proving the existence of pure Nash equilibria (PNE) in the unrelated parallel links setting; in the network setting, the finite improvement property collapses as soon as we depart from linear delays, but there is an exact potential (and thus PNE) for linear delays. The price of anarchy on identical parallel links demonstrates a quite surprising threshold behavior: It persists on being asymptotically equal to that in the case of the noncooperative KP-model, unless the number of coalitions is
sublogarithmic
.

We also show crucial differences, mainly concerning the hardness of algorithmic problems that are solved efficiently in the noncooperative case. Although we demonstrate convergence to robust PNE, we also prove the hardness of computing them. On the other hand, we propose a generalized fully mixed Nash equilibrium that can be efficiently constructed in most cases. Finally, we propose a natural improvement policy and prove its convergence in pseudopolynomial time to PNE which are robust against (even dynamically forming) coalitions of small size.
Integrated droplet routing and defect tolerance in the synthesis of digital microfluidic biochips
Authors: Xu Tao , Chakrabarty Krishnendu
Published: August 2008

Microfluidic biochips are revolutionizing high-throughput DNA sequencing, immunoassays, and clinical diagnostics. As high-throughput bioassays are mapped to digital microfluidic platforms, the need for design automation techniques is being increasingly felt. Moreover, as most applications of biochips are safety-critical in nature, defect tolerance is an essential system attribute. Several synthesis tools have recently been proposed for the automated design of biochips from the specifications of laboratory protocols. However, only a few of these tools address the problem of defect tolerance. In addition, most of these methods do not consider the problem of droplet routing in microfluidic arrays. These methods typically rely on postsynthesis droplet routing to implement biochemical protocols. Such an approach is not only time consuming, but also imposes an undue burden on the chip user. Postsynthesis droplet routing does not guarantee that feasible droplet pathways can be found for area-constrained biochip layouts; nonroutable fabricated biochips must be discarded. We present a synthesis tool that integrates defect tolerance and droplet routing in the design flow. Droplet routability, defined as the ease with which droplet pathways can be determined, is estimated and integrated in the synthesis procedure. Presynthesis and postsynthesis defect-tolerance methods are also presented. We use a large-scale protein assay as a case study to evaluate the proposed synthesis method.
COVER STORYToto, I've got a feeling we're not in Kansas anymore…
Authors: Davis Meredith
Published: August 2008

Editor's Note: Meredith's critique---adapted from her opening keynote address of the 2008 AIGA Massaging Media 2 conference---speaks to design education beyond the boundaries of graphic design. Our thanks to Hugh Dubberly for bringing her speech to our attention.
Regulation of Akt signaling byO-GlcNAc in euglycemia
Authors: Soesanto Yudi A. , Luo Bai , Jones Deborah , Taylor Rodrick , Gabrielsen J. Scott , Parker Glendon , McClain Donald A.
Published: August 2008

The hexosamine biosynthesis pathway (HBP) regulates the posttranslational modification of nuclear and cytoplasmic protein by O-linked N-acetylglucosamine ( O-GlcNAc). Numerous studies have demonstrated that, in hyperglycemic conditions, excessive glucose flux through this pathway contributes to the development of insulin resistance. The role of the HBP in euglycemia, however, remains largely unknown. Here we investigated the effect of O-GlcNAc on hepatic Akt signaling at physiological concentrations of glucose. In HepG2 cells cultured in 5 mM glucose, removal of O-GlcNAc by adenoviral-mediated overexpression of O-GlcNAcase increased Akt activity and phosphorylation. We also observed that Akt was recognized by succinylated wheat germ agglutinin (sWGA), which specifically binds O-GlcNAc. Overexpression of O-GlcNAcase in HepG2 cells reduced the levels of Akt in sWGA precipitates. The increased Akt activity was accompanied by increased phosphorylation of Akt substrates and reduced mRNA for glucose-6-phosphatase and phospho enolpyruvate carboxykinase (PEPCK). The increased Akt activity was not a result of activation of its upstream activator phosphoinositide 3-kinase (PI 3-kinase). Further demonstrating Akt regulation by O-GlcNAc, we found that overexpression of O-GlcNAcase in the livers of euglycemic mice also significantly increased Akt activity, resulting in increased phosphorylation of downstream targets and decreased mRNA for glucose-6-phosphatase. Together, these data suggest that O-GlcNAc regulates Akt signaling in hepatic models under euglycemic conditions.
Phosphorylation of IRS proteins, insulin action, and insulin resistance
Authors: Boura-Halfon Sigalit , Zick Yehiel
Published: August 2008

Insulin signaling at target tissues is essential for growth and development and for normal homeostasis of glucose, fat, and protein metabolism. Control over this process is therefore tightly regulated. It can be achieved by a negative feedback control mechanism whereby downstream components inhibit upstream elements along the insulin-signaling pathway (autoregulation) or by signals from apparently unrelated pathways that inhibit insulin signaling thus leading to insulin resistance. Phosphorylation of insulin receptor substrate (IRS) proteins on serine residues has emerged as a key step in these control processes under both physiological and pathological conditions. The list of IRS kinases implicated in the development of insulin resistance is growing rapidly, concomitant with the list of potential Ser/Thr phosphorylation sites in IRS proteins. Here, we review a range of conditions that activate IRS kinases to phosphorylate IRS proteins on “hot spot” domains. The flexibility vs. specificity features of this reaction is discussed and its characteristic as an “array” phosphorylation is suggested. Finally, its implications on insulin signaling, insulin resistance and type 2 diabetes, an emerging epidemic of the 21st century are outlined.
Relationship between AMPK and the transcriptional balance of clock-related genes in skeletal muscle
Authors: Vieira Elaine , Nilsson Elisabeth C. , Nerstedt Annika , Ormestad Mattias , Long Yun Chau , Garcia-Roves Pablo M. , Zierath Juleen R. , Mahlapuu Margit
Published: August 2008

Circadian clocks coordinate physiological, behavioral, and biochemical events with predictable daily environmental changes by a self-sustained transcriptional feedback loop. CLOCK and ARNTL are transcriptional activators that regulate Per and Cry gene expression. PER and CRY inhibit their own transcription, and their turnover allows this cycle to restart. The transcription factors BHLHB2 and BHLHB3 repress Per activation, whereas orphan nuclear receptors of the NR1D and ROR families control Arntl expression. Here we show the AMP-activated protein kinase (AMPK)γ3 subunit is involved in the regulation of peripheral circadian clock function. AMPKγ3 knockout ( Prkag3−/−) mice or wild-type littermates were injected with saline or an AMPK activator, 5-amino-4-imidazole-carboxamide riboside (AICAR), and white glycolytic gastrocnemius muscle was removed for gene expression analysis. Genes involved in the regulation of circadian rhythms ( Cry2, Nr1d1, and Bhlhb2) were differentially regulated in response to AICAR in wild-type mice but remained unaltered in Prkag3−/− mice. Basal expression of Per1 was higher in Prkag3−/− mice compared with wild-type mice. Distinct diurnal changes in the respiratory exchange ratio (RER) between the light and dark phase of the day were observed in wild-type mice but not Prkag3−/− mice. In summary, the expression profile of clock-related genes in skeletal muscle in response to AICAR, as well as the diurnal shift in energy utilization, is impaired in AMPKγ3 subunit knockout mice. Our results indicate AMPK heterotrimeric complexes containing the AMPKγ3 subunit may play a specific role in linking circadian oscillators and energy metabolism in skeletal muscle.
Synaptic Transmission From the Supratrigeminal Region to Jaw-Closing and Jaw-Opening Motoneurons in Developing Rats
Authors: Nakamura Shiro , Inoue Tomio , Nakajima Kan , Moritani Masayuki , Nakayama Kiyomi , Tokita Kenichi , Yoshida Atsushi , Maki Kohtaro
Published: August 2008

The supratrigeminal region (SupV) receives abundant orofacial sensory inputs and descending inputs from the cortical masticatory area and contains premotor neurons that target the trigeminal motor nucleus (MoV). Thus it is possible that the SupV is involved in controlling jaw muscle activity via sensory inputs during mastication. We used voltage-sensitive dye, laser photostimulation, patch-clamp recordings, and intracellular biocytin labeling to investigate synaptic transmission from the SupV to jaw-closing and jaw-opening motoneurons in the MoV in brain stem slice preparations from developing rats. Electrical stimulation of the SupV evoked optical responses in the MoV. An antidromic optical response was evoked in the SupV by MoV stimulation, whereas synaptic transmission was suppressed by substitution of external Ca2+ with Mn2+. Photostimulation of the SupV with caged glutamate evoked rapid inward currents in the trigeminal motoneurons. Gramicidin-perforated and whole cell patch-clamp recordings from masseter motoneurons (MMNs) and digastric motoneurons (DMNs) revealed that glycinergic and GABAergic postsynaptic responses evoked in MMNs and DMNs by SupV stimulation were excitatory in P1–P4 neonatal rats and inhibitory in P9–P12 juvenile rats, whereas glutamatergic postsynaptic responses evoked by SupV stimulation were excitatory in both neonates and juveniles. Furthermore, the axons of biocytin-labeled SupV neurons that were antidromically activated by MoV stimulation terminated in the MoV. Our results suggest that inputs from the SupV excite MMNs and DMNs through activation of glutamate, glycine, and GABAA receptors in neonates, whereas glycinergic and GABAergic inputs from the SupV inhibit MMNs and DMNs in juveniles.
Response of the adipose tissue transcriptome to dihydrotestosterone in mice
Authors: Zhang Yonghua , Calvo Ezequiel , Martel Céline , Luu-The Van , Labrie Fernand , Tchernof André
Published: August 2008

Androgens have been postulated to be important modulators of adipose tissue metabolism and fat cell function. In the present study, we investigated the response of male and female mice retroperitoneal adipose tissue to the nonaromatizable androgen dihydrotestosterone (DHT). Adipose tissue samples were obtained in gonadectomized animals treated with vehicle (control group), or injected with 0.1 mg DHT 1, 3, 6, 12, 18, and 24 h prior to necropsy. Fourteen animals were pooled at each time point (total 196 animals). Transcripts that were significantly modulated were considered as androgen-responsive genes. Quantitative real-time RT-PCR was used to confirm results from the microarray analysis in a subset of 46 probe sets in male mice and 98 probe sets in female mice. Considering peak time vs. control, we confirmed 74.0 and 63.3% of the modulated genes by PCR in males and females, respectively. Four genes were significantly stimulated in a similar manner by DHT in both sexes, namely metallothionein 1, growth arrest and DNA-damage-inducible 45 gamma, cyclin-dependent kinase inhibitor 1A, and fk506-binding protein 5. All these genes appear to be involved in the regulation of adipocyte differentiation/proliferation and adipogenesis. In conclusion, this study, which evaluated the acute transcriptome response of adipose tissue to DHT in male and female mice, suggests that DHT consistently modulates genes involved in the regulation of adipogenesis in retroperitoneal adipose tissue of both male and female animals.
Polar Body-Based Preimplantation Genetic Diagnosis for N-Acetylglutamate Synthase Deficiency
Authors: Altarescu G. , Brooks B. , Eldar-Geva T. , Margalioth E.J. , Singer A. , Levy-Lahad E. , Renbaum P.
Published: August 2008

Objective: We describe a sensitive and highly reliable preimplantation genetic diagnosis (PGD) assay for N-acetylglutamate synthetase (NAGS) deficiency using polar body (PB) analysis in conjunction with multiple markers flanking the gene. This rare autosomal recessive mitochondrial disorder is characterized by hyperammonemia, uncontrollable movements, developmental delay, visual impairment, failure to thrive and vomiting and is caused by mutations in the NAGS gene located on chromosome 17q21.31. Methods: For a family with an affected child we have developed a multiplex fluorescent PCR protocol that included detection of the specific familial mutation (2729insC) in conjunction with the analysis of five informative polymorphic markers flanking the gene: D17S902, D17S965, D17S1861, D17S791 and D17S1868. Following successful amplification in single-cell fibroblasts, this protocol was used in the couple carriers of NAGS mutation. Results: Of 18 retrieved eggs, 16 were at the M2 stage and 9 fertilized. 12 polar body 1s (PB1) were heterozygotes, 1 homozygote wild-type, 1 total amplification failure, and two showed inconclusive results. Three oocytes that had heterozygote PB1s showed mutant polar body 2 (PB2) indicating a wild-type oocyte. Despite the fact that the specific 2729insC mutation did not amplify in the PGD cycle, analysis of linked markers in PBs was sufficient to ensure an accurate diagnosis in 5 out of 9 oocytes. This cycle resulted in the transfer of 3 embryos originating from oocytes diagnosed as wild-type by PB analysis, with the subsequent birth of healthy twin girls. Postnatal genetic testing revealed that both girls harbored the healthy maternal allele and carried the mutant paternal allele. Conclusions: Our multiplex-nested PCR protocol based on several linked microsatellite markers offers an efficient and accurate method for PGD for NAGS syndrome even when the mutation is not amplified.
Prenatal Diagnosis of a Retroperitoneal Lymphangioma: A Case and Review
Authors: Hachisuga Masahiro , Tsukimori Kiyomi , Hojo Satoshi , Hidaka Nobuhiro , Yoshimura Takazumi , Masumoto Kouji , Taguchi Tomoaki , Wake Norio
Published: August 2008

Prenatal sonographic findings of lymphangiomas characteristically appear as thin-walled, multiseptate hypoechogenic masses. In our case, a retroperitoneal hypoechogenic mass was detected at 26 weeks of gestation by sonography. Serial sonographic examinations demonstrated multiple septations at 29 weeks of gestation, which in retrospect was a classical finding of retroperitoneal lymphangioma. MRI at 38 weeks of gestation revealed a multilocular mass, which was homogeneous, low on T1-weighted and high on T2-weighted images, in the left retroperitoneal cavity. These findings were compatible with the diagnosis of a lymphangioma. This case shows the change in characteristic imaging features, from a unilocular to multilocular pattern, of a lymphangioma with regard to gestational age. It is important to observe the size and extension of such tumors in order to determine the prospect for neonatal prognosis, as well as to make decisions on the delivery timing and style.
Fetal Microphthalmia Diagnosed by Magnetic Resonance Imaging
Authors: Paquette L. , Randolph L. , Incerpi M. , Panigrahy A.
Published: August 2008

We report a case of fetal microphthalmia diagnosed midtrimester by ultrasound and fetal MRI. Included is a comparison of MRI measurements of normal fetuses at similar gestational age and a review of the literature.
Uptake and Release of Fluoride from Fluoride-Impregnated Chewing Sticks (Miswaks) in vitro and in vivo
Authors: Baeshen H.A. , Kjellberg H. , Lingström P. , Birkhed D.
Published: August 2008

The purpose was to investigate the uptake and release of fluoride (F) from F-impregnated chewing sticks (miswaks). In the first series, 3-cm-long pieces were impregnated in 1, 2, 3 and 4% NaF solutions for 3 h, 1 day and 3 days (10 pieces/test). There was a dose-response effect with respect to both impregnation time and the concentration of the F solution. In the second and third series, totally 40 miswak pieces were impregnated in 3% NaF for 1 day and 3 days; the outer layer (bark) was separated from the inner spongy part (pulp) and analyzed separately. F was released from both parts, but somewhat more was released from the bark than from the pulp; a plateau was reached at around 30 min. In vivo, 9 healthy subjects used three products for 2 min in a crossover design: (1) a miswak impregnated in 3% NaF for 1 day, (2) a miswak impregnated in 3% NaF for 3 days, and (3) 1 g of F toothpaste (containing 1,450 ppm F as NaF) on a toothbrush. The highest F concentration at the approximal area was obtained after using the miswak impregnated in 3% NaF for 3 days compared with the other products (p < 0.05 or p < 0.01). To conclude, NaF-impregnated miswaks produced a rapid release of F in vitro as well as in vivo and may be an interesting vehicle for home care use for caries prevention in countries where they are used regularly.
Weather as a Trigger of Stroke
Authors: Jimenez-Conde J. , Ois A. , Gomis M. , Rodriguez-Campello A. , Cuadrado-Godia E. , Subirana I. , Roquer J.
Published: August 2008

Background: The conclusions of previous studies show little agreement concerning the relationship between weather and the incidence of stroke. We analyse the relationship between daily meteorological conditions and daily as well as seasonal stroke incidence. Methods: 1,286 consecutive strokes assessed during 3 years (2001–2003) from the reference area of Hospital del Mar were classified as intracerebral haemorrhage (ICH) (n = 243) or ischaemic stroke (IS) (n = 1,043). IS was divided in non-lacunar stroke (NLS) (n = 732) and lacunar stroke (LS) (n = 311). Daily meteorological data were obtained from ‘Observatori Fabra’ of Barcelona: atmospheric pressure (AP), relative humidity, maximum, minimum, and mean temperatures, and the variation of all these measures compared with the previous day. Results: Total stroke (TS) incidence showed little association with AP (coefficient of confidence, CC: –0.072; p = 0.022), but was higher with the AP variations (CC: 0.127; p < 0.001). NLS were related to AP falls (OR: 2.41; p < 0.001) whilst ICHs were associated with AP rises (OR: 2.07; p = 0.01). NLS and temperature showed an inverse correlation; however, it lost its significance after adjusting for AP variations. The daily incidences of NLS and ICH were higher in autumn and in winter, but depended strongly on the daily variations of AP. No other associations were found. Conclusions: The incidences of NLS and ICH are related to AP changes compared with the previous day. AP changes largely explain the seasonal and daily variations in the incidence of stroke. These data may help to explain the controversy in previous studies and to promote studies focused on the trigger mechanisms of stroke.
Early Neurological Deterioration following Intravenous Recombinant Tissue Plasminogen Activator Therapy in Patients with Acute Lacunar Stroke
Authors: Hwang Yang-Ha , Seo Jong-Geun , Lee Ho-Won , Park Sung-Pa , Suh Chung-Kyu
Published: August 2008

Background: The aim of this study was to examine the rate of early neurological deterioration (END) and favorable outcomes after acute lacunar stroke following the use of intravenous recombinant tissue plasminogen activator (IV rtPA). Methods: A total of 76 acute lacunar stroke patients (<12 h from symptom onset) were enrolled during a 1-year period (n = 76). Comparisons were made between those who received (group A; n = 29) or did not receive (group B; n = 47) IV rtPA. Results: END/favorable outcomes were observed in 24/31% of the subjects in group A and 21/23% in group B (p = 0.77/0.46). Subgroup analysis of the etiologic subtype of small-vessel occlusion showed that END/favorable outcomes were observed in about 33/33% and 15/19% of the patients in groups A and B, respectively (p = 0.21/0.34). Conclusions: The authors showed that the use of rtPA in cases of no lysible clots might not affect the END and favorable outcomes.
The JNK Inhibitor XG-102 Protects from Ischemic Damage with Delayed Intravenous Administration Also in the Presence of Recombinant Tissue Plasminogen Activator
Authors: Wiegler Karine , Bonny Christophe , Coquoz Didier , Hirt Lorenz
Published: August 2008

Background: XG-102 (formerly D-JNKI1), a TAT-coupled dextrogyre peptide which selectively inhibits the c-Jun N-terminal kinase, is a powerful neuroprotectant in mouse models of middle cerebral artery occlusion (MCAo) with delayed intracerebroventricular injection. We aimed to determine whether this neuroprotection could also be achieved by intravenous injection of XG-102, which is a more feasible approach for future use in stroke patients. We also tested the compatibility of the compound with recombinant tissue plasminogen activator (rtPA), commonly used for intravenous thrombolysis and known to enhance excitotoxicity. Methods: Male ICR-CD1 mice were subjected to a 30-min-suture MCAo. XG-102 was injected intravenously in a single dose, 6 h after ischemia. Hippocampal slice cultures were subjected to oxygen (5%) and glucose (1 mM) deprivation for 30 min. rtPA was added after ischemia and before XG-102 administration, both in vitro and in vivo. Results: The lowest intravenous dose achieving neuroprotection was 0.0003 mg/kg, which reduced the infarct volume after 48 h from 62 ± 19 mm3 (n = 18) for the vehicle-treated group to 18 ± 9 mm3 (n = 5, p < 0.01). The behavioral outcome was also significantly improved at two doses. Addition of rtPA after ischemia enhanced the ischemic damage both in vitro and in vivo, but XG-102 was still able to induce a significant neuroprotection. Conclusions: A single intravenous administration of XG-102 several hours after ischemia induces a powerful neuroprotection. XG-102 protects from ischemic damage in the presence of rtPA. The feasibility of systemic administration of this promising compound and its compatibility with rtPA are important steps for its development as a drug candidate in ischemic stroke.
Ischemic Findings of T2*-Weighted 3-Tesla MRI in Acute Stroke Patients
Authors: Morita Naomi , Harada Masafumi , Uno Masaaki , Matsubara Shunji , Matsuda Tsuyoshi , Nagahiro Shinji , Nishitani Hiromu
Published: August 2008

Background: We compared ischemic findings on gradient echo-type T2*-weighted images at 3-tesla MRI (T2*WI) in patients with acute ischemia and major vessel occlusion, and stroke patients with lacunar infarction or branch atheromatous disease. Methods: Our study population consisted of 45 patients with acute stroke. They underwent 3-tesla MRI within 12 h of stroke onset. Included were 24 patients (13 men and 11 women, mean age 68 years) with major vessel occlusion and 21 patients (11 men and 10 women, mean age 69 years) with minor infarction such as lacunar infarcts or branch atheromatous disease. We classified vascular ischemic findings of T2*WI into 3 sign categories, i.e. artery susceptibility sign, cortical vessel sign (hypointensity and enlargement of the cortical vessels) and brush sign (hypointensity of vessels in the deep white matter). Decreased intensity in the ischemic parenchyma was designated ischemic tissue sign. We compared regions of interest in the hypoperfused area on flow-sensitive alternating inversion recovery (FAIR) images with our vascular ischemic findings. Results: None of the vascular ischemic signs nor the ischemic tissue sign were found in patients with minor vessel disease. All 24 patients with major vessel occlusion manifested the cortical vessel sign, 23 the brush sign. The area with ischemic vessel signs on T2*WI was almost as large or somewhat smaller than the hypoperfused area on FAIR images. Compared to the contralateral side, 14 of 24 patients (58.3%) with major vessel occlusion showed decreased intensity in the ischemic parenchyma (ischemic tissue sign). Region of interest measurements on FAIR images demonstrated greater hypoperfusion in the area classified as ischemic tissue sign on T2*WI. Conclusions: Ischemic vessel signs and the ischemic tissue sign on T2*WI at 3 T would be useful to evaluate the extensive ischemia due to major vessel occlusion and may be correlated with the blood-oxygen-level-dependent effect due to increased deoxyhemoglobin. The ischemic tissue sign may be reflective of severe ischemia.