bluuebunny/crossref_metadata_2025 huggingface dataset:
α-Synuclein–induced Aggregation of Cytoplasmic Vesicles inSaccharomyces cerevisiae
Authors: Soper James H. , Roy Subhojit , Stieber Anna , Lee Eliza , Wilson Robert B. , Trojanowski John Q. , Burd Christopher G. , Lee Virginia M.-Y.
Published: January 2008

Aggregated α-synuclein (α-syn) fibrils form Lewy bodies (LBs), the signature lesions of Parkinson's disease (PD) and related synucleinopathies, but the pathogenesis and neurodegenerative effects of LBs remain enigmatic. Recent studies have shown that when overexpressed in Saccharomyces cerevisiae, α-syn localizes to plasma membranes and forms cytoplasmic accumulations similar to human α-syn inclusions. However, the exact nature, composition, temporal evolution, and underlying mechanisms of yeast α-syn accumulations and their relevance to human synucleinopathies are unknown. Here we provide ultrastructural evidence that α-syn accumulations are not comprised of LB-like fibrils, but are associated with clusters of vesicles. Live-cell imaging showed α-syn initially localized to the plasma membrane and subsequently formed accumulations in association with vesicles. Imaging of truncated and mutant forms of α-syn revealed the molecular determinants and vesicular trafficking pathways underlying this pathological process. Because vesicular clustering is also found in LB-containing neurons of PD brains, α-syn–mediated vesicular accumulation in yeast represents a model system to study specific aspects of neurodegeneration in PD and related synucleinopathies.
Course of relational and non-relational recognition memory across the adult lifespan
Authors: Soei Eleonore , Daum Irene
Published: January 2008

Human recognition memory shows a decline during normal ageing, which is thought to be related to age-associated dysfunctions of mediotemporal lobe structures. Whether the hippocampus is critical for human general relational memory or for spatial relational memory only is still disputed. The human perirhinal cortex is thought to be critically involved in non-relational memory, but another view postulates hippocampal involvement in both relational and non-relational memory. Investigating whether there is a differential impact of ageing on these memory processes may shed further light into these issues. Thus, in the present study, 106 healthy adults performed three recognition memory tasks in a consecutive age groups design involving a range from age 20 to 76. This allowed the separate assessment of spatial and nonspatial relational memory as well as non-relational memory. Both spatial and nonspatial relational memory declined in the 66–76 yr group. This pattern is consistent with the presumed course of hippocampal changes across normal ageing and points to the hippocampal role in relational memory in general. An impairment of non-relational memory commenced earlier in the 51–65 yr group. This finding is discussed in relation to perceptual/attentional mediation of memory and its potential brain correlates in ageing.
Is the medial amygdala part of the neural circuit modulating conditioned defeat in Syrian hamsters?
Authors: Markham Chris M. , Huhman Kim L.
Published: January 2008

Conditioned defeat is a model wherein hamsters that have previously experienced a single social defeat subsequently exhibit heightened levels of avoidance and submission in response to a smaller, non-aggressive intruder. While we have previously demonstrated the critical involvement of the basolateral and central nuclei of the amygdala in the acquisition and expression of conditioned defeat, the role of the medial amygdala has yet to be investigated. In Experiment 1, muscimol, a GABAA receptor agonist, was infused bilaterally into the MeA prior to initial defeat training. Experiment 2 examined the effects of muscimol injections given prior to subsequent testing with a non-aggressive intruder. Finally, in Experiment 3, anisomycin was used to block protein synthesis in the medial and basolateral amygdala to examine the involvement of these nuclei in memory consolidation related to conditioned defeat. Submissive behavior was significantly reduced in animals that received muscimol prior to initial defeat training as well as in animals injected prior to testing with the non-aggressive intruder, indicating that the MeA is necessary for the acquisition and expression of conditioned defeat. In Experiment 3, however, anisomycin reduced conditioned defeat only when administered into the BLA, and not when injected into the MeA. The results of the present series of experiments suggest that, while the MeA may serve an important gateway for sensory information that is crucial for conditioned defeat, it does not appear to play a role in the plasticity including this behavioral response to social defeat.
A new concept of mountain building
Authors: BARBER TONY
Published: January 2008

Mountain belts are constructed over periods of hundreds of millions of years from unrelated fragments carried across the ocean basins from distant sites, to be accreted along continental margins. Continental collision is an incidental rather than a necessary requirement for orogeny. Palaeogeographical reconstructions using the present geographical relationships of the fragments which make up orogenic belts are doomed to failure.
Kinematic indicators: structures that record the sense of movement in mountain chains
Authors: SUGDEN TIM
Published: January 2008

The relationship between the structure of mountain chains and plate tectonics is complex and poorly understood. Growing interest in large and small‐scale structures ‐ kinematic indicators ‐which record the sense of flow in rocks, may help to solve some of the outstanding problems.
High roads and low roads
Authors: CARTER PAUL , WALLACE GUS
Published: January 2008

One of the joys in working as an engineering geologist on Scottish road schemes is the variety of geology that has to be dealt with, from soft silts to hard metamorphics. The properties of these materials must be assessed, cuttings and embankments designed, and site work monitored carefully to ensure safe and economic construction.
The Black Country Geological Society
Authors: Gardens St Nicolas
Published: January 2008

Britain has been noted for its local geological societies since the great amateur geology boom of the 19th century. Many such societies (old, new or re‐formed) still exist. But what is their role in the 1980s? We asked Paul Shilston to describe the history and current activities of The Black Country Geological Society, of which he is Honorary Secretary.
The destruction of Iapetus and Tornquist's Oceans
Authors: PICKERING KEVIN T.
Published: January 2008

The Cambro‐Ordovician Iapetus and Tornquist's Oceans formed a Pacific‐type ocean basin rimmed by volcanic island arcs and marginal basins. By the latest Ordovician to earliest Silurian this ocean basin was beginning to close, to become a Mediterranean‐type ocean basin. This was caused by the collision between a microcontinent (comprising England, Wales, much of Ireland and parts of north‐west Europe), called Eastern Avalonia, and the North American super‐continent, Laurentia, which resulted in no oceanic crust remaining in the region of present‐day central Newfoundland. Marine basins, however, persisted into the Middle Silurian. Throughout the Silurian and early Devonian, some 40–45 million years, various terranes continued to collide with the North American margin, predominantly under major left‐lateral strike‐slip until the remaining seaways were eliminated in the early Middle Devonian, to be replaced by terrestrial environments of the Old Red Sandstone.
The Medusa effect: instantaneous fossilization
Authors: MARTILL DAVID M.
Published: January 2008

Rapid fossilization of fishes and other animals in the Lower Cretaceous of the Chapada do Araripe, north‐east Brazil, has preserved the most delicate structures known in the fossil record. Gills, muscles, stomachs and even eggs with yolks have been found. Interestingly, the material is not particularly rare, and specimens can be purchased from your local rock shop.
Prospects at Parys Mountain
Authors: WESTHEAD STEPHEN J.
Published: January 2008

Parys Mountain, a small hill in north‐east Anglesey, North Wales, has a very long history of copper mining, although exploration from 1955 onwards failed to locate deposits that were economic in modern terms. However, more detailed studies since the early 1980s have revealed a much more promising prospect.
The local geologist 6: The fossil trade
Authors: TAYLOR MICHAEL A.
Published: January 2008

What do you do if a professional collector starts fossicking in your favourite quarry? Call the police? English Nature? The local museum? Or perhaps nip round with the cheque book to get that crinoid you always wanted for the study wall? The correct answer could be any or all of these; professional fossil collecting is an activity with very real costs which are often outweighed by the benefits. It depends who's collecting what, where and when.
Exploring the deep‐sea floor in the 1990s and beyond
Authors: SUMMERHAYES C. P.
Published: January 2008

What does the future hold for marine geology?
The Soom Shale: a unique Ordovician fossil horizon in South Africa
Authors: ALDRIDGE RICHARD J. , THERON JOHANNES N. , GABBOTT SARAH E.
Published: January 2008

The recent discovery of fossils with preserved soft tissues in the Cedarberg Mountains of the Cape Province has opened a new window on Ordovician life.
ULTRAVIOLET‐INDUCED APOCHLOROSIS AND PHOTOREACTIVATION IN TWO STRAINS OF EUGLENA GRACILIS*
Authors: Cook J. R.
Published: January 2008

Abstract— Very low doses of ultraviolet irradiation result in a complete loss of the ability to synthesize chlorophyll in two closely related strains of Euglena gracilis (var. hacillaris and strain Z). Both strains are equally sensitive in this response under non‐photoreactivating conditions. The ability to synthesize chlorophyll is completely photoreactivated by visible light in E. grncilis var. bacillaris, even after lethal doses of u.v.: the Z strain. however, while photoreactivable following low doses of u.v., remains bleached after doses adequate to kill only 10–20 per cent of the cells.
EFFECTS OF U.V. ON DNA: CORRELATIONS AMONG BIOLOGICAL CHANGES, PHYSICAL CHANGES AND REPAIR MECHANISMS*
Authors: Setlow Jane K.
Published: January 2008

Summary It is very probable that thymine dimers account for most, but not all, of the inactivation of transforming DNA in aqueous solution by u.v. radiation. The experiments on enzymatic photoreactivation of transforming DNA require postulating at least two photoreactivable lesions, one the thymine dimer, and a second, which apparently does not itself affect transforming activity but does affect the kinetics of the increase in transforming activity in photoreactivation. Action spectra suggest that alteration of cytosine deoxyriboside may be important in non‐photoreactivable inactivation of DNA. Some cells have such efficient repair mechanisms for removal of thymine dimers that this kind of damage can have little if anything to do with their inactivation.
On 24 Forms of the Acoustic Wave Equation in Vortical Flows and
Dissipative Media
Authors: Campos L. M. B. C.
Published: January 2008

The 36 forms of the acoustic wave equation derived in an earlier review (Campos, L. M. B. C., 2007, “On 36 Forms of the Acoustic Wave Equation in Potential Flows and Inhomogeneous Media,” Appl. Mech. Rev., 60, pp. 149–171) were grouped in four classes, of which the last (Class IV) concerned sheared mean flows; another type of vortical flow is swirling flow, and thus the present review completes the preceding by starting with Class V of linear, nondissipative acoustic wave equations in axisymmetric swirling, and also sheared, mean flow. These include general swirl and, in particular, rigid body and potential vortex swirl, combined or not with shear, for axisymmetric or general nonaxisymmetric acoustic modes, in two types of media: (i) inhomogeneous isentropic and (ii) homogeneous homentropic. Besides the 14 acoustic wave equations in sheared and swirling mean flows, the remaining ten acoustic wave equations derived in the present review all concern waves in homogeneous and steady media at rest, with dissipation or nonlinear effects to second-order or a combination of these two opposing effects, viz., (i) Class VI of linear, nondissipative wave equations with weak or strong thermoviscous dissipation in a homogeneous medium at rest; (ii) Class VIIA nonlinear one-dimensional wave equations in steady, homogeneous medium at rest without dissipation, or with viscous or thermoviscous dissipation, also in the case of a duct of varying cross section; (iii) Class VIIB of weakly nonlinear, three-dimensional waves or beams with thermoviscous dissipation in a homogeneous steady medium at rest. The 24 forms of the acoustic wave equation derived in the present review add to the 36 forms in the preceding review to form the set of 60 acoustic wave equations, whose interconnections are indicated in a family tree at the end. Numerous examples of the applications of the wave equations to the physical world are given at the end of each written section.
Modeling the imaging performance of prototype organic x‐ray imagers
Authors: Blakesley J. C. , Speller R.
Published: January 2008

A unified Monte Carlo and cascaded systems model for the simulation of active‐matrix flat‐panel imagers is presented. With few input parameters, the model simulated the imaging performance of previously measured flat‐panel imagers with reasonable accuracy. The model is used to predict the properties of conceptual flat‐panel imagers based on organic semiconductors on plastic substrates. The model suggests that significant improvements in resolution and detective quantum efficiency could be achieved by operating such a detector in a back‐side illuminated configuration, or by employing two imaging arrays arranged face‐to‐face. The effect of semiconductor properties on the conceptual imagers is investigated. According to the model, a photodiode quantum efficiency of and dark current of less than would be satisfactory for a prototype imager, while a competitive imager would require a photodiode quantum efficiency of with a dark current of less than to be quantum limited over the radiographic exposure range.
Evaluation of the effect of patient dose from cone beam computed tomography on prostate IMRT using Monte Carlo simulation
Authors: Chow James C. L. , Leung Michael K. K. , Islam Mohammad K. , Norrlinger Bernhard D. , Jaffray David A.
Published: January 2008

The aim of this study is to evaluate the impact of the patient dose due to the kilovoltage cone beam computed tomography (kV‐CBCT) in a prostate intensity‐modulated radiation therapy (IMRT). The dose distributions for the five prostate IMRTs were calculated using the Pinnacle3 treatment planning system. To calculate the patient dose from CBCT, phase‐space beams of a CBCT head based on the ELEKTA x‐ray volume imaging system were generated using the Monte Carlo BEAMnrc code for 100, 120, 130, and 140 kVp energies. An in‐house graphical user interface called DOSCTP (DOSXYZnrc‐based) developed using MATLAB was used to calculate the dose distributions due to a photon arc from the CBCT beam with the same patient CT image sets as used in Pinnacle3. The two calculated dose distributions were added together by setting the CBCT doses equal to , , , and of the prescription dose of the prostate IMRT. The prostate plan and the summed dose distributions were then processed in the CERR platform to determine the dose‐volume histograms (DVHs) of the regions of interest. Moreover, dose profiles along the ‐ and ‐axes crossing the isocenter with and without addition of the CBCT dose were determined. It was found that the added doses due to CBCT are most significant at the femur heads. Higher doses were found at the bones for a relatively low energy CBCT beam such as 100 kVp. Apart from the bones, the CBCT dose was observed to be most concentrated on the anterior and posterior side of the patient anatomy. Analysis of the DVHs for the prostate and other critical tissues showed that they vary only slightly with the added CBCT dose at different beam energies. On the other hand, the changes of the DVHs for the femur heads due to the CBCT dose and beam energy were more significant than those of rectal and bladder wall. By analyzing the vertical and horizontal dose profiles crossing the femur heads and isocenter, with and without the CBCT dose equal to of the prescribed dose, it was found that there is about a increase of dose at the femur head. Still, such an increase in the femur head dose is well below the dose limit of the bone in our IMRT plans. Therefore, under these dose fractionation conditions, it is concluded that, though CBCT causes a higher dose deposited at the bones, there may be no significant effect in the DVHs of critical tissues in the prostate IMRT.
Energy‐range relation and mean energy variation in therapeutic particle beams
Authors: Kempe Johanna , Brahme Anders
Published: January 2008

Analytical expressions for the mean energy and range of therapeutic light ion beams and low‐ and high‐energy electrons have been derived, based on the energy dependence of their respective stopping powers. The new mean energy and range relations are power‐law expressions relevant for light ion radiation therapy, and are based on measured practical ranges or known tabulated stopping powers and ranges for the relevant incident particle energies. A practical extrapolated range, , for light ions was defined, similar to that of electrons, which is very closely related to the extrapolated range of the primary ions. A universal energy‐range relation for light ions and electrons that is valid for all material mixtures and compounds has been developed. The new relation can be expressed in terms of the range for protons and alpha particles, and is found to agree closely with experimental data in low atomic number media and when the difference in the mean ionization energy is low. The variation of the mean energy with depth and the new energy‐range relation are useful for accurate stopping power and mass scattering power calculations, as well as for general particle transport and dosimetry applications.
Hypofractionation in radiation therapy and its impact
Authors: Papiez Lech , Timmerman Robert
Published: January 2008

A brief history of the underlying principles of the conventional fractionation in radiation therapy is discussed, followed by the formulation of the hypothesis for hypofractionated stereotactic body radiation therapy (SBRT). Subsequently, consequences of the hypothesis for SBRT dose shaping and dose delivery techniques are sketched. A brief review of the advantages of SBRT therapy in light of the existing experience is then provided. Finally, the need for new technological developments is advocated to make SBRT therapies more practical, safer, and clinically more effective. It is finally concluded that hypofractionated SBRT treatment will develop into a new paradigm that will shape the future of radiation therapy by providing the means to suppress the growth of most carcinogen‐induced carcinomas and by supporting the cure of the disease.
Dosimetric impact of motion in free‐breathing and gated lung radiotherapy: A 4D Monte Carlo study of intrafraction and interfraction effects
Authors: Seco Joao , Sharp Greg C. , Wu Ziji , Gierga David , Buettner Florian , Paganetti Harald
Published: January 2008

The purpose of this study was to investigate if interfraction and intrafraction motion in free‐breathing and gated lung IMRT can lead to systematic dose differences between 3DCT and 4DCT. Dosimetric effects were studied considering the breathing pattern of three patients monitored during the course of their treatment and an in‐house developed 4D Monte Carlo framework. Imaging data were taken in free‐breathing and in cine mode for both 3D and 4D acquisition. Treatment planning for IMRT delivery was done based on the free‐breathing data with the CORVUS (North American Scientific, Chatsworth, CA) planning system. The dose distributions as a function of phase in the breathing cycle were combined using deformable image registration. The study focused on (a) assessing the accuracy of the CORVUS pencil beam algorithm with Monte Carlo dose calculation in the lung, (b) evaluating the dosimetric effect of motion on the individual breathing phases of the respiratory cycle, and (c) assessing intrafraction and interfraction motion effects during free‐breathing or gated radiotherapy. The comparison between (a) the planning system and the Monte Carlo system shows that the pencil beam algorithm underestimates the dose in low‐density regions, such as lung tissue, and overestimates the dose in high‐density regions, such as bone, by or more of the prescribed dose (corresponding to approximately 3–5 Gy for the cases considered). For the patients studied this could have a significant impact on the dose volume histograms for the target structures depending on the margin added to the clinical target volume (CTV) to produce either the planning target (PTV) or internal target volume (ITV). The dose differences between (b) phases in the breathing cycle and the free‐breathing case were shown to be negligible for all phases except for the inhale phase, where an underdosage of the tumor by as much as 9.3 Gy relative to the free‐breathing was observed. The large difference was due to breathing‐induced motion/deformation affecting the soft/lung tissue density and motion of the bone structures (such as the rib cage) in and out of the beam. Intrafraction and interfraction dosimetric differences between (c) free‐breathing and gated delivery were found to be small. However, more significant dosimetric differences, of the order of , were observed between the dose calculations based on static CT (3DCT) and the ones based on time‐resolved CT (4DCT). These differences are a consequence of the larger contribution of the inhale phase in the 3DCT data than in the 4DCT.
Ion Beam Science: Solved and Unsolved Problems (Part I, II)
Authors: Jeraj Robert
Published: January 2008

Ion Beam Science: Solved and Unsolved Problems (Part I, II) Sigmund P. Special‐Trykkeriet Viborg a‐s, Denmark, 2006. Price: 350 DKK (Danish Krone). ISSN: 0023‐3323. ISBN: 10 87‐7304‐330‐3; ISBN: 13 978‐7304‐330‐1, 376 pp. (Part I), 384 pp. (Part II).
Ongoing in Vivo Experience Triggers Synaptic Metaplasticity in the Neocortex
Authors: Clem Roger L. , Celikel Tansu , Barth Alison L.
Published: January 2008

In vivo experience can occlude subsequent induction of long-term potentiation and enhance long-term depression of synaptic responses. Although a reduced capacity for synaptic strengthening may function to prevent excessive excitation, such an effect paradoxically implies that continued experience or training should not improve and may even degrade neural representations. In mice, we examined the effect of ongoing whisker stimulation on synaptic strengthening at layer 4-2/3 synapses in the barrel cortex. Although
N
-methyl-
d
-aspartate receptors were required to initiate strengthening, they subsequently suppressed further potentiation at these synapses in vitro and in vivo. Despite this transition, synaptic strengthening continued with additional sensory activity but instead required the activation of metabotropic glutamate receptors, suggesting a mechanism by which continued experience can result in increasing synaptic strength over time.
Intermittent Plate Tectonics?
Authors: Silver Paul G. , Behn Mark D.
Published: January 2008

Although it is commonly assumed that subduction has operated continuously on Earth without interruption, subduction zones are routinely terminated by ocean closure and supercontinent assembly. Under certain circumstances, this could lead to a dramatic loss of subduction, globally. Closure of a Pacific-type basin, for example, would eliminate most subduction, unless this loss were compensated for by comparable subduction initiation elsewhere. Given the evidence for Pacific-type closure in Earth's past, the absence of a direct mechanism for termination/initiation compensation, and recent data supporting a minimum in subduction flux in the Mesoproterozoic, we hypothesize that dramatic reductions or temporary cessations of subduction have occurred in Earth's history. Such deviations in the continuity of plate tectonics have important consequences for Earth's thermal and continental evolution.
The Avalon Explosion: Evolution of Ediacara Morphospace
Authors: Shen Bing , Dong Lin , Xiao Shuhai , Kowalewski Michał
Published: January 2008

Ediacara fossils [575 to 542 million years ago (Ma)] represent Earth's oldest known complex macroscopic life forms, but their morphological history is poorly understood. A comprehensive quantitative analysis of these fossils indicates that the oldest Ediacara assemblage—the Avalon assemblage (575 to 565 Ma)—already encompassed the full range of Ediacara morphospace. A comparable morphospace range was occupied by the subsequent White Sea (560 to 550 Ma) and Nama (550 to 542 Ma) assemblages, although it was populated differently. In contrast, taxonomic richness increased in the White Sea assemblage and declined in the Nama assemblage. These diversity changes, occurring while morphospace range remained relatively constant, led to inverse shifts in morphological variance. The Avalon morphospace expansion mirrors the Cambrian explosion, and both events may reflect similar underlying mechanisms.
Heterochromatin and RNAi Are Required to Establish CENP-A Chromatin at Centromeres
Authors: Folco Hernan Diego , Pidoux Alison L. , Urano Takeshi , Allshire Robin C.
Published: January 2008

Heterochromatin is defined by distinct posttranslational modifications on histones, such as methylation of histone H3 at lysine 9 (H3K9), which allows heterochromatin protein 1 (HP1)–related chromodomain proteins to bind. Heterochromatin is frequently found near CENP-A chromatin, which is the key determinant of kinetochore assembly. We have discovered that the RNA interference (RNAi)–directed heterochromatin flanking the central kinetochore domain at fission yeast centromeres is required to promote CENP-A
Cnp1
and kinetochore assembly over the central domain. The H3K9 methyltransferase Clr4 (Suv39); the ribonuclease Dicer, which cleaves heterochromatic double-stranded RNA to small interfering RNA (siRNA); Chp1, a component of the RNAi effector complex (RNA-induced initiation of transcriptional gene silencing; RITS); and Swi6 (HP1) are required to establish CENP-A
Cnp1
chromatin on naïve templates. Once assembled, CENP-A
Cnp1
chromatin is propagated by epigenetic means in the absence of heterochromatin. Thus, another, potentially conserved, role for centromeric RNAi-directed heterochromatin has been identified.
Learn and play with interactive TV
Authors: Chorianopoulos Konstantinos , Lekakos George
Published: January 2008

Despite the criticism concerning the value of TV content, research reveals several worthwhile aspects -- one of them is the opportunity to learn. In this article we explore the characteristics of interactive TV applications that facilitate education and interactive entertainment. In doing so we analyze research methods and empirical results from experimental and field studies. The findings suggest that interactive TV applications provide support for education and entertainment for children and young people, as well as continuous education for all. In particular, interactive TV is especially suitable for (1) informal learning and (2) for engaging and motivating its audience. We conclude with an agenda for future interactive TV research in entertainment and education.
Approximating stationary measures of structured continuous-time Markov models using matrix diagrams
Authors: Ciardo Gianfranco , Miner Andrew S. , Wan Min , Yu Andy Jinqing
Published: January 2008

We consider the stationary solution of large ergodic continuous-time Markov chains (CTMCs) with a finite state space
S
, i.e., the computation of π as solution of π ·
Q
= 0 subject to ∑

i
ε
s

π[
i
] = 1, where
Q
coincides with transition rate matrix
R
except in its diagonal elements,
Q
[
i, i
] = - ∑

j
ε
s

R
[
i, j
].
Gibberellin Metabolism and its Regulation
Authors: Yamaguchi Shinjiro
Published: January 2008

Bioactive gibberellins (GAs) are diterpene plant hormones that are biosynthesized through complex pathways and control diverse aspects of growth and development. Biochemical, genetic, and genomic approaches have led to the identification of the majority of the genes that encode GA biosynthesis and deactivation enzymes. Recent studies have highlighted the occurrence of previously unrecognized deactivation mechanisms. It is now clear that both GA biosynthesis and deactivation pathways are tightly regulated by developmental, hormonal, and environmental signals, consistent with the role of GAs as key growth regulators. In some cases, the molecular mechanisms for fine-tuning the hormone levels are beginning to be uncovered. In this review, I summarize our current understanding of the GA biosynthesis and deactivation pathways in plants and fungi, and discuss how GA concentrations in plant tissues are regulated during development and in response to environmental stimuli.
Magnetohydrodynamic Turbulence at Low Magnetic Reynolds Number
Authors: Knaepen Bernard , Moreau René
Published: January 2008

This article reviews the main established ideas on the influence of a magnetic field on turbulence in electrically conducting fluids. We limit our discussion to the asymptotic range of very small values of the magnetic Reynolds number, characterized by the fact that the induced magnetic field remains very small in comparison with the applied magnetic field. We consider three kinds of flows here. The simplest one is freely decaying homogeneous turbulence, which serves as a test bed to analyze the development of anisotropy resulting from the linear damping by the Lorentz force. We then discuss flows between walls perpendicular to the magnetic field and emphasize the influence of the Hartmann layers that develop in their vicinity. We then review the main features of the possible quasi-two-dimensional regime that can arise in that context. Finally, we consider magnetohydrodynamic turbulent shear flows. These are frequent in industrial applications involving molten metals, such as in metal processing or in the blanket of future nuclear fusion reactors. We pay particular attention to recent attempts to develop specific RANS (Reynolds-averaged Navier-Stokes) models for these flows.
Applications of Acoustics and Cavitation to Noninvasive Therapy and Drug Delivery
Authors: Coussios Constantin C. , Roy Ronald A.
Published: January 2008

Biomedical acoustics is rapidly evolving from a diagnostic modality into a therapeutic tool, and acoustic cavitation is often the common denominator in a wide range of new therapeutic applications. High-intensity focused ultrasound (HIFU) waves generated outside the body can be used to deposit heat deep within the body. Through a quantitative analysis of heat deposition by ultrasound, it is shown that inertial cavitation can help address some of the major challenges of HIFU therapy by providing a means of enhancing and monitoring treatment noninvasively. In the context of drug delivery, both inertial and stable cavitation play roles in enhancing drug activity and uptake. In particular, shape oscillations arising during stable cavitation provide an effective micropumping mechanism for enhanced mass transport across inaccessible interfaces.
Effects of Wind on Plants
Authors: de Langre Emmanuel
Published: January 2008

This review surveys the large variety of mechanical interactions between wind and plants, from plant organs to plant systems. These interactions range from leaf flutter to uprooting and seed dispersal, as well as indirect effects on photosynthesis or insect communication. I first estimate the relevant nondimensional parameters and then discuss turbulence, plant dynamics, and the mechanisms of interaction in this context. Some common features are identified and analyzed in relation to the wind engineering of manmade structures. Strong coupling between plants and wind exists, in which the plant motion modifies the wind dynamics. I also present some related biological issues in which the relation between plant life and wind environment is emphasized.

[V]oici la lourde nappe/Et la profonde houle et l’océan des blés

[Like a sheet/The deep swell on a sea of wheat]

Charles Péguy (1873–1914)
Mechanics and Prediction of Turbulent Drag Reduction with Polymer Additives
Authors: White Christopher M. , Mungal M Godfrey
Published: January 2008

This article provides a review of recent progress in understanding and predicting polymer drag reduction (DR) in turbulent wall-bounded shear flows. The reduction in turbulent friction losses by the dilute addition of high–molecular weight polymers to flowing liquids has been extensively studied since the phenomenon was first observed over 60 years ago. Although it has long been reasoned that the dynamical interactions between polymers and turbulence are responsible for DR, it was not until recently that progress had been made to begin to elucidate these interactions in detail. These advancements come largely from numerical simulations of viscoelastic turbulent flows and detailed turbulence measurements in flows of dilute polymer solutions using laser-based optical techniques. This review presents a selective overview of the current state of the numerics and experimental techniques and their impact on understanding the mechanics and prediction of polymer DR. It includes a discussion of areas in which our understanding is incomplete, warranting further study.
Choreography of Cell Motility and Interaction Dynamics Imaged by Two-Photon Microscopy in Lymphoid Organs
Authors: Cahalan Michael D. , Parker Ian
Published: January 2008

The immune system is the most diffuse cellular system in the body. Accordingly, long-range migration of cells and short-range communication by local chemical signaling and by cell-cell contacts are vital to the control of an immune response. Cellular homing and migration within lymphoid organs, antigen recognition, and cell signaling and activation are clearly vital during an immune response, but these events had not been directly observed in vivo until recently. Introduced to the field of immunology in 2002, two-photon microscopy is the method of choice for visualizing living cells deep within native tissue environments, and it is now revealing an elegant cellular choreography that underlies the adaptive immune response to antigen challenge. We review cellular dynamics and molecular factors that contribute to basal motility of lymphocytes in the lymph node and cellular interactions leading to antigen capture and recognition, T cell activation, B cell activation, cytolytic effector function, and antibody production.
The Role of Politics in Economic Development
Authors: Gourevitch Peter
Published: January 2008

How have economic historians understood the role of politics in shaping country differences in economic development? An impressive recent literature can be sorted out according to the degree of “human agency” at work. At the low-agency end are perspectives that stress geography, which is unalterable, leaving little room for human action and hence no room for politics. At the other end are arguments stressing deliberate, self-aware actions, hence choice, hence a substantial role for politics. In between are arguments where some choice occurred in the past or at a specific moment, but little since then. What drives development? Two lines of argument are vigorously debated: explanations that stress human capital and explanations that stress institutions. Within each camp can be found variance on the degree of agency and hence on the role of politics. Both vary as well on how they envisage society and its interaction with both institutions and human capital.
Co-Benefits of Climate Mitigation and Health Protection in Energy Systems: Scoping Methods
Authors: Smith Kirk R. , Haigler Evan
Published: January 2008

Interventions in the energy sector offer significant opportunities for reducing both greenhouse and other health-damaging pollution, resulting in what are called “co-benefits.” The health community plays a critical role in evaluating such interventions to optimize progress of both sorts because both affect health. In detail, analyses require sophisticated modeling and specific local information. As a starting point, however, we offer here a set of scoping methods for obtaining a quick assessment of these co-benefits for interventions in the energy sector, the arena with the highest potential for significant co-benefits. Thus we combine relevant methods developed separately in recent years for cost-effectiveness assessments in the climate change, health, and development communities. We offer sample calculations, which illustrate the apparent high degree of co-benefit effectiveness for targeted interventions in the household energy sector in developing countries.
Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ
Authors: Makita Ryosuke , Uchijima Yasunobu , Nishiyama Koichi , Amano Tomokazu , Chen Qin , Takeuchi Takumi , Mitani Akihisa , Nagase Takahide , Yatomi Yutaka , Aburatani Hiroyuki , Nakagawa Osamu , Small Erin V. , Cobo-Stark Patricia , Igarashi Peter , Murakami Masao , Tominaga Junji , Sato Takahiro , Asano Tomoichiro , Kurihara Yukiko , Kurihara Hiroki
Published: January 2008

TAZ (transcriptional coactivator with PDZ-binding motif), also called WWTR1 (WW domain containing transcription regulator 1), is a 14-3-3-binding molecule homologous to Yes-associated protein. TAZ acts as a coactivator for several transcription factors as well as a modulator of membrane-associated PDZ domain-containing proteins, but its (patho)physiological roles remain unknown. Here we show that gene inactivation of TAZ in mice resulted in pathological changes in the kidney and lung that resemble the common human diseases polycystic kidney disease and pulmonary emphysema. Taz-null/ lacZ knockin mutant homozygotes demonstrated renal cyst formation as early as embryonic day 15.5 with dilatation of Bowman's capsules and proximal tubules, followed by pelvic dilatation and hydronephrosis. After birth, only one-fifth of TAZ-deficient homozygotes grew to adulthood and demonstrated multicystic kidneys with severe urinary concentrating defects and polyuria. Furthermore, adult TAZ-deficient homozygotes exhibited diffuse emphysematous changes in the lung. Thus TAZ is essential for developmental mechanisms involved in kidney and lung organogenesis, whose disturbance may lead to the pathogenesis of common human diseases.
Common Input to Motor Units of Intrinsic and Extrinsic Hand Muscles During Two-Digit Object Hold
Authors: Winges Sara A. , Kornatz Kurt W. , Santello Marco
Published: January 2008

Anatomical and physiological evidence suggests that common input to motor neurons of hand muscles is an important neural mechanism for hand control. To gain insight into the synaptic input underlying the coordination of hand muscles, significant effort has been devoted to describing the distribution of common input across motor units of extrinsic muscles. Much less is known, however, about the distribution of common input to motor units belonging to different intrinsic muscles and to intrinsic-extrinsic muscle pairs. To address this void in the literature, we quantified the incidence and strength of near-simultaneous discharges of motor units residing in either the same or different intrinsic hand muscles (m. first dorsal, FDI, and m. first palmar interosseus, FPI) during two-digit object hold. To extend the characterization of common input to pairs of extrinsic muscles (previous work) and pairs of intrinsic muscles (present work), we also recorded electromyographic (EMG) activity from an extrinsic thumb muscle (m. flexor pollicis longus, FPL). Motor-unit synchrony across FDI and FPI was weak (common input strength, CIS, mean ± SE: 0.17 ± 0.02). Similarly, motor units from extrinsic-intrinsic muscle pairs were characterized by weak synchrony (FPL-FDI: 0.25 ± 0.02; FPL-FPI: 0.29 ± 0.03) although stronger than FDI-FPI. Last, CIS from within FDI and FPI was more than three times stronger (0.70 ± 0.06 and 0.66 ± 0.06, respectively) than across these muscles. We discuss present and previous findings within the framework of muscle-pair specific distribution of common input to hand muscles based on their functional role in grasping.
Quantitative trait loci for physical activity traits in mice
Authors: Lightfoot J. Timothy , Turner Michael J. , Pomp Daniel , Kleeberger Steven R. , Leamy Larry J.
Published: January 2008

The genomic locations and identities of the genes that regulate voluntary physical activity are presently unknown. The purpose of this study was to search for quantitative trait loci (QTL) that are linked with daily mouse running wheel distance, duration, and speed of exercise. F2animals ( n = 310) derived from high active C57L/J and low active C3H/HeJ inbred strains were phenotyped for 21 days. After phenotyping, genotyping with a fully informative single-nucleotide polymorphism panel with an average intermarker interval of 13.7 cM was used. On all three activity indexes, sex and strain were significant factors, with the F2animals similar to the high active C57L/J mice in both daily exercise distance and duration of exercise. In the F2cohort, female mice ran significantly farther, longer, and faster than male mice. QTL analysis revealed no sex-specific QTL but at the 5% experimentwise significance level did identify one QTL for duration, one QTL for distance, and two QTL for speed. The QTL for duration ( DUR13.1) and distance ( DIST13.1) colocalized with the QTL for speed ( SPD13.1). Each of these QTL accounted for ∼6% of the phenotypic variance, whereas SPD9.1 (chromosome 9, 7 cM) accounted for 11.3% of the phenotypic variation. DUR13.1, DIST13.1, SPD13.1, and SPD9.1 were subsequently replicated by haplotype association mapping. The results of this study suggest a genetic basis of voluntary activity in mice and provide a foundation for future candidate gene studies.
RASSF1APolymorphism A133S Is Associated with Early Onset Breast Cancer inBRCA1/2Mutation Carriers
Authors: Gao Boning , Xie Xian-Jin , Huang Chunxian , Shames David S. , Chen Tina T-L. , Lewis Cheryl M. , Bian Aihua , Zhang Bifeng , Olopade Olufunmilayo I. , Garber Judy E. , Euhus David M. , Tomlinson Gail E. , Minna John D.
Published: January 2008

The tumor suppressor gene RASSF1A regulates cell cycle progression, apoptosis, and microtubule stability and is inactivated by promoter methylation in ∼50% of breast cancers. It has been shown previously that the polymorphism A133S in RASSF1A reduces its ability to regulate cell cycle progression and this polymorphism is associated with an increased risk of breast cancer. We analyzed the frequency of RASSF1A A133S in 190 Caucasian women without breast cancer and 653 patients with breast cancer including 138 BRCA1 and BRCA2 (BRCA1/2) mutation carriers, 395 non–BRCA1/2 mutations carriers, and 120 untested for BRCA1/2 mutations. Patients with breast cancer had a higher frequency of A133S than the controls [P = 0.017; odds ratios (OR), 1.71; 95% confidence intervals (95% CI), 1.10–2.66]. There is also a higher frequency of A133S in patients with higher familial breast cancer risk (P = 0.029; OR, 1.76; 95% CI, 1.06–2.92) and patients carrying BRCA1/2 mutations (P = 0.037, OR, 1.82; 95% CI, 1.04–3.18). Importantly, we found that the co-occurrence of a BRCA1 or BRCA2 mutation and A133S in RASSF1A was associated with earlier onset of breast cancer compared with those individuals with either a BRCA1/2 mutation or the A133S polymorphism alone (36.0 versus 42.0 years old, P = 0.002). Our data suggest that the presence of the RASSF1A A133S polymorphism is associated with breast cancer pathogenesis in general and modifies breast cancer age of onset in BRCA1/2 mutations carriers. Our results warrant a large-scale study to examine the effect of the A133S polymorphism in the development of breast and other types of cancers. [Cancer Res 2008;68(1):22–5]
Radiotherapy in Lung Adenocarcinoma with Brain Metastases: Effects of Activating Epidermal Growth Factor Receptor Mutations on Clinical Response
Authors: Gow Chien-Hung , Chien Chun-Ru , Chang Yih-Leong , Chiu Yueh-Hsia , Kuo Sung-Hsin , Shih Jin-Yuan , Chang Yeun-Chung , Yu Chong-Jen , Yang Chih-Hsin , Yang Pan-Chyr
Published: January 2008

Purpose: Whole-brain radiation therapy (WBRT) has been applied to inoperable brain metastases in lung adenocarcinoma. Recently, an in vitro study showed reduced clonogenic survival of mutant epidermal growth factor receptor (EGFR) lung cancer cell lines in response to ionizing radiation compared with that of the wild type. To elucidate the role of EGFR mutations in radiation treatment, we evaluated the clinical response to WBRT and survival of lung adenocarcinoma patients with brain metastases.

Experimental Design: This was a retrospective analysis of 63 patients with brain metastases from lung adenocarcinoma who were treated with WBRT. Demographic data, EGFR mutation status, response to WBRT, and survival data were collected. Clinical response was assessed 1 month after the start of WBRT. Univariate and logistic regression models were used to test potential predictive factors associated with clinical response. Log-rank test and Cox regression were analyzed to identify factors that affected survival.

Results: Clinical response to WBRT was observed in 29 patients (46%), with 34 nonresponder patients (54%). Patients with EGFR mutations had higher response rates to WBRT compared with those with the wild-type (54% versus 24%; P = 0.045). Both the administration of EGFR tyrosine kinase inhibitor (P = 0.034) and EGFR mutation (P = 0.029) were independently associated with response to WBRT. In Cox regression analysis, WBRT responder (P = 0.010) and absence of extracranial metastases (P = 0.002) were associated with better survival.

Conclusions: Both the EGFR mutations and the administration of EGFR TKI during WBRT were independent predictors of response to WBRT in brain metastases of lung adenocarcinoma.
Blocking Vascular Endothelial Growth Factor-A Inhibits the Growth of Pituitary Adenomas and Lowers Serum Prolactin Level in a Mouse Model of Multiple Endocrine Neoplasia Type 1
Authors: Korsisaari Nina , Ross Jed , Wu Xiumin , Kowanetz Marcin , Pal Navneet , Hall Linda , Eastham-Anderson Jeffrey , Forrest William F. , Van Bruggen Nicholas , Peale Franklin V. , Ferrara Napoleone
Published: January 2008

Purpose: Multiple endocrine neoplasia type 1 (MEN1) is defined clinically by the combined occurrence of multiple tumors, typically of the parathyroid glands, pancreatic islet cells, and anterior pituitary gland. A mouse model with a heterozygous deletion of the Men1 gene recapitulates the tumorigenesis of MEN1. We wished to determine the role of vascular endothelial growth factor (VEGF)-A in the vascularization and growth of MEN1-associated tumors, with an emphasis on pituitary adenomas.

Experimental Design: To investigate whether tumor growth in Men1+/− mice is mediated by VEGF-A dependent angiogenesis, we carried out a monotherapy with the anti–VEGF-A monoclonal antibody (mAb) G6-31. We evaluated tumor growth by magnetic resonance imaging and assessed vascular density in tissue sections. We also measured hormone levels in the serum.

Results: During the treatment with mAb G6-31, a significant inhibition of the pituitary adenoma growth was observed, leading to an increased mean tumor doubling-free survival compared with mice treated with a control antibody. Similarly, the growth of s.c. pituitary adenoma transplants was effectively inhibited by administration of anti–VEGF-A mAb. Serum prolactin was lowered by mAb G6-31 treatment but not by control antibody, potentially providing a new therapeutic approach for treating the hormonal excess in MEN1 patients. Additionally, the vascular density in pancreatic islet tumors was significantly reduced by the treatment.

Conclusions: These results suggest that VEGF-A blockade may represent a nonsurgical treatment for benign tumors of the endocrine system.