bluuebunny/crossref_metadata_2025 huggingface dataset:
Isomerization dynamics and ergodicity in Ar7
Authors: Miller Mark A. , Wales David J.
Published: July 2002

The isomerization dynamics of a model Ar7 cluster, bound by the pairwise Lennard–Jones potential, are examined in the melting and liquid-like regions. We use molecular dynamics with frequent quenching to calculate the accumulated residence times and distribution of lifetimes in each of the four geometrical isomers as a function of the microcanonical energy. The residence times are compared with the ratios of the density of states associated with the isomers, evaluated by microcanonical Monte Carlo simulations, and are in good agreement. The distribution of lifetimes is found to be exponential (Poissonian) except at very short times. We propose and test a simple explanation for this behavior in terms of rapid recrossings of the dividing surface. The energy dependence of the individual isomerization rates is compared with the predictions of RRK theory through a knowledge of the transition states. We discuss the results in the light of a recent study that addressed the issue of ergodicity in this system.
Strict detailed balance is unnecessary in Monte Carlo simulation
Authors: Manousiouthakis Vasilios I. , Deem Michael W.
Published: July 2002

Detailed balance is an overly strict condition to ensure a valid Monte Carlo simulation. We show that, under fairly general assumptions, a Monte Carlo simulation need satisfy only the weaker balance condition. Not only does our proof show that sequential updating schemes are correct, but also it establishes the correctness of a whole class of new methods that simply leave the Boltzmann distribution invariant.
Gauge invariant coupled cluster response theory
Authors: Pedersen Thomas Bondo , Koch Henrik , Hättig Christof
Published: July 2002

We introduce a time-dependent coupled cluster based Lagrangian that includes orbital rotation. This Lagrangian is shown to give gauge invariant response properties for one-electron operators in the limit of a complete one-electron basis. The pole structure of the linear response function is compatible with that of the exact response function and the notorious problem of unphysical second-order poles in the Brueckner coupled cluster response theory is not present in this model. The total energy of the model is identical to the coupled cluster model using optimized orbitals recently revived by Sherrill et al. [J. Chem. Phys. 109, 4171 (1998)]. The model provides a straightforward approach for calculating magnetic response properties in a gauge invariant manner using coupled cluster type wave functions.
Vibrationally resolved photoelectron spectroscopy of the first row transition metal and C3 clusters: MC3− (M=Sc, V, Cr, Mn, Fe, Co, and Ni)
Authors: Wang Lai-Sheng , Li Xi
Published: July 2002

We report photoelectron spectra of the MC3− clusters for M=Sc, V, Cr, Mn, Fe, Co, and Ni at two photon energies, 355 and 266 nm. Vibrational structure is resolved for the ground and excited state detachment transitions for all the clusters except for CoC3− and NiC3−. Electron affinity (EA) and vibrational frequencies for the MC3 clusters are obtained. Complicated low-lying excited state features are observed for all the species. We find that the trend of the EA across the 3d series for the MC3 clusters is similar to that of the MC2 species. The vibrational frequency is found to increase from ScC3 to TiC3 and then decreases monotonically to the right of the 3d series. Preliminary density functional theory calculations are performed on all the MC3 and MC3− clusters at several initial geometries and spin multiplicities. We find that the ground states of all the MC3 and MC3− species have C2v ring structures. The calculated M–C stretching frequency for all the MC3 species is in good agreement with the experimental measurement, lending credence to the obtained C2v structure.
Level-one representations and vertex operators of quantum affine superalgebra Uq[gl(N̂|N)]
Authors: Zhang Yao-Zhong
Published: July 2002

Level-one representations of the quantum affine superalgebra Uq[gl(N̂|N)] associated with the appropriate nonstandard system of simple roots and q-vertex operators (intertwining operators) associated with the level-one modules are constructed explicitly in terms of free bosonic fields.
Raman investigations of orientational ordering in NiSiF6⋅6H2O, NiSiF6⋅6D2O, and ZnSiF6⋅6H2O crystals
Authors: Eremenko V. V. , Peschanskii A. V. , Fomin V. I.
Published: July 2002

The results of investigations of polarized Raman spectra in ZnSiF6⋅6H2O and NiSiF6⋅6D2O single crystals in the temperature range 2–300 K are presented. It is found that the crystals are orientationally ordered at low temperatures. The orientational disordering is described by a model in which the rotational motion of the SiF62− complex is determined by a two-well asymmetric potential function. The parameters of the model are determined from the temperature behavior of the Raman spectral lines. The calculated values of concentration for two orientational positions of the SiF62− complex at room temperature are in good agreement with the x-ray data.
Hydrodynamic theory for the magnetization current in a collisionless plasma
Authors: Aliev Yu. M. , Frolov A. A. , Stenflo L. , Shukla P. K.
Published: July 2002

It is demonstrated that the magnetization current, which arises from the interaction of high-frequency electromagnetic waves with hot collisionless, unmagnetized electron plasmas, can be derived by means of the ten-moment system of hydrodynamic equations. It is pointed out that the magnetization current is solely associated with the thermal motion of the electrons, and that it therefore does not appear in cold plasmas. This expression for the magnetization current agrees with those derived previously from kinetic theory. The present derivation provides, however, a comparatively much clearer physical picture of the origin of this current. In the limit where the phase velocity is much larger than the electron thermal velocity, a new result for the high-frequency induced vorticity of the plasma is obtained. It is also shown that the magnetization current in this paper is responsible for a novel scattering mechanism in which the high-frequency electromagnetic waves are scattered off vortex motions.
Self-similar invariant families of turbulent flows
Authors: Foias C. , Manley O. P. , Teman R.
Published: July 2002

Some physically significant consequences of recent advances in the theory of homogeneous statistical solutions of Navier–Stokes equations are presented. Invariance properties of families of those solutions are discussed and used to derive rigorously certain previously conjectured results, e.g., the Kolmogorov spectrum. Others include a reinterpretation of the von Karman–Howarth–Dryden equation that leads to the conditions for the existence of an inertial subrange. Further an application of Poincaré’s inequality produces a different view of intermittency. It is also suggested how a measurement of the two-point triple velocity correlation could yield an accurate value of Kolmogorov’s constant.
Relativistic fluid equations for intense electron beams
Authors: Siambis John G.
Published: July 2002

A general, covariant, four-space relativistic fluid formulation has been obtained that is not limited to small thermal effects. The four-space formulation has been transformed to a three-space formulation which further reduces to the set of relativistic fluid equations given by Newcomb [Phys. Fluids 25, 846 (1982)] for the case of small thermal effects. A new and important relativistic macroscopic fluid parameter has been defined and evaluated in general. This is the thermal velocity relativistic rest mass factor λ, first introduced approximately by Newcomb. The factor λ plays a role similar to the single particle relativistic rest mass factor γ and the fluid velocity relativistic rest mass factor Γ. For a relativistic fluid the effective relativistic rest mass factor is the product of λ and Γ. The factor λ has been expressed in terms of the normalized beam emittance, thereby permitting direct evaluation of λ from beam experimental data. High-quality beams are characterized by extremely low emittance values, thereby resulting in values for λ of order 1. The regime of λ large is also an interesting one, particularly in cases where beam directed energy is rapidly being converted, through elastic collisional interactions, to beam thermal energy such as in beam–solid target or beam–dense plasma interactions.
Bubble growth and stability in an effective porous medium
Authors: Li X. , Yortsos Y. C.
Published: July 2002

This paper examines the in situ growth and stability of a single bubble in an effective porous medium, where the pore microstructure is neglected. The main objective of the study is the effect of mass transfer and flow parameters on bubble stability. Because it is necessary for flow in both phases to be considered, this is actually a generalized phase-change problem involving two fluids in a porous medium. Similarity solutions are developed in both three-dimensional (3-D) and two-dimensional (2-D) geometries, the stability of which is subsequently analyzed. In the absence of capillarity, an instability analogous to Mullins–Sekerka is found, which is independent of the process parameters, including the viscosity ratio, M. Capillary effects are next considered for the 2-D geometry of a Hele–Shaw cell (the analysis is also extended to 3-D geometries). At the large M limit, the stability condition is identical to Patterson’s [J. Fluid Mech. 113, 513 (1981)] for the displacement of a liquid by a gas. This theory is found consistent with bubble growth experiments in Hele–Shaw cells. At finite M, the theory predicts that the interface becomes more stable as M increases, which is directly opposite to the effect of M in viscous fingering. This is a novel mechanism of convective stabilization and it is intrinsic to in situ phase growth. Higher solubility and diffusion coefficients also have a stabilizing effect. For conditions typical to bubble growth, however, the sensitivity to these parameters is very weak.
Stability of bootstrap current-driven magnetic islands in stellarators
Authors: Hegna C. C. , Callen J. D.
Published: July 2002

The stability of magnetic island producing perturbations due to fluctuations in the bootstrap current in stellarator configuration is examined. The stability criterion depends on the sign of the derivative of the rotational transform, the pressure gradient, and the direction of the equilibrium bootstrap current, which is determined by the structure of ‖B‖. It is found that quasihelically symmetric stellarator configurations with p′/ι′<0 are unstable to the formation of bootstrap current-driven magnetic islands. The stability of conventional stellarator configurations depends upon the field structure.
Dispersive properties of a magnetized plasma with a field-aligned drift and inhomogeneous transverse flow
Authors: Gavrishchaka V. , Koepke M. E. , Ganguli G.
Published: July 2002

Electrostatic fluctuations driven by the combination of a magnetic-field-aligned electron current and a localized transverse electric field are investigated. Characteristic parameters, such as scale length and magnitude of the sheared E×B velocity, magnitude of the magnetic-field-aligned current, and temperature ratio τ≡Ti/Te are varied to include conditions associated with electrostatic waves driven entirely by magnetic-field-aligned current, driven entirely by transverse electric field, and driven by a combination of magnetic-field-aligned current and transverse electric field. It is shown that, in contrast to the homogeneous case of current-driven modes, the modes in the presence of a transverse-velocity shear can be unstable in a wider range of temperature ratio τ and they are broadband in frequency. Using a simplified model, numerical solutions of the nonlocal dispersion relation, and physical arguments, cases of stabilization and destabilization due to the inhomogeneous energy-density driven instability mechanism are studied for the ion-cyclotron, ion-acoustic and drift modes. The response of the plasma to transverse-velocity shear can be categorized as reactive or dissipative and conditions corresponding to the predominance of either one are evaluated. Possible applications of these results to space and laboratory plasma are discussed.
Nonlinear theory of collisionless trapped ion modes
Authors: Hahm T. S. , Tang W. M.
Published: July 2002

A simplified two-field nonlinear model for collisionless trapped-ion-mode turbulence has been derived from nonlinear bounce-averaged drift kinetic equations. The renormalized thermal diffusivity obtained from this analysis exhibits a Bohm-like scaling. A new nonlinearity associated with the neoclassical polarization density is found to introduce an isotope-dependent modification to this Bohm-like diffusivity. The asymptotic balance between the equilibrium variation and the finite banana width-induced reduction of the fluctuation potential leads to the result that the radial correlation length decreases with increasing plasma current. Other important conclusions from the present analysis include the predictions that (i) the relative density fluctuation level δn/n0 is lower than the conventional mixing length estimate, Δr/Ln; (ii) the ion temperature fluctuation level δTi/Ti significantly exceeds the density fluctuation level δn/n0; and (iii) the parallel ion velocity fluctuation level δvi∥/vTi is expected to be negligible.
A review of astrophysics experiments on intense lasers
Authors: Remington Bruce A. , Drake R. Paul , Takabe Hideaki , Arnett David
Published: July 2002

Astrophysics has traditionally been pursued at astronomical observatories and on theorists’ computers. Observations record images from space, and theoretical models are developed to explain the observations. A component often missing has been the ability to test theories and models in an experimental setting where the initial and final states are well characterized. Intense lasers are now being used to recreate aspects of astrophysical phenomena in the laboratory, allowing the creation of experimental testbeds where theory and modeling can be quantitatively tested against data. We describe here several areas of astrophysics—supernovae, supernova remnants, gamma-ray bursts, and giant planets—where laser experiments are under development to test our understanding of these phenomena.
Low-temperature organometallic vapor phase epitaxial growth of CdTe using a new organotellurium source
Authors: Kisker D. W. , Steigerwald M. L. , Kometani T. Y. , Jeffers K. S.
Published: July 2002

The growth of CdTe by organometallic vapor phase epitaxy has been accomplished at 250 °C, using a new tellurium source, dimethylditelluride. The compound decomposes at a much lower temperature than the corresponding monotelluride, apparently by reacting with a cadmium-containing species to eliminate one tellurium atom. As a result, the temperature necessary for deposition of CdTe has been lowered from the range of 400 °C, thus making completely thermally driven chemical vapor deposition of II-VI compounds possible at much lower temperatures.
Coinciding early activation of the human primary visual cortex and anteromedial cuneus
Authors: Vanni Simo , Tanskanen Topi , Seppä Mika , Uutela Kimmo , Hari Riitta
Published: July 2002

Proper understanding of processes underlying visual perception
requires information on the activation order of distinct brain areas.
We measured dynamics of cortical signals with magnetoencephalography
while human subjects viewed stimuli at four visual quadrants. The
signals were analyzed with minimum current estimates at the individual
and group level. Activation emerged 55–70 ms after stimulus onset both
in the primary posterior visual areas and in the anteromedial part of
the cuneus. Other cortical areas were active after this initial dual
activation. Comparison of data between species suggests that the
anteromedial cuneus either comprises a homologue of the monkey area V6
or is an area unique to humans. Our results show that visual stimuli
activate two cortical areas right from the beginning of the cortical
response. The anteromedial cuneus has the temporal position needed to
interact with the primary visual cortex V1 and thereby to modify
information transferred via V1 to extrastriate cortices.
Mapping the evolution of regional atrophy in Alzheimer's disease: Unbiased analysis of fluid-registered serial MRI
Authors: Scahill Rachael I. , Schott Jonathan M. , Stevens John M. , Rossor Martin N. , Fox Nick C.
Published: July 2002

Alzheimer's disease (AD) is characterized by progressive cerebral atrophy, which may be assessed by using volumetric MRI. We describe a voxel-based analysis of nonlinear-registered serial MRI to demonstrate the most statistically significant (
P
< 0.001) regions of change at different stages of the disease. We compared presymptomatic (
n
= 4), mild (
n
= 10), and moderately affected (
n
= 12) patients with early- and late-onset AD, with age- and sex-matched controls, and demonstrated increasing global atrophy with advancing disease. Significantly increased rates of hippocampal atrophy were seen in presymptomatic and mildly affected patients. There was a shift in the distribution of temporal lobe atrophy with advancing disease; the inferolateral regions of the temporal lobes showed the most significantly increased rates of atrophy by the time the patients were mildly or moderately affected. Significantly increased rates of medial parietal lobe atrophy were seen at all stages, with frontal lobe involvement occurring later in the disease. Our results suggest that the sites showing the most significant rates of atrophy alter as the disease advances, and that regional atrophy is already occurring before the onset of symptoms. This technique provides insights into the natural history of AD, and may be a valuable tool in assessing the efficacy of disease-modifying treatments, especially if these treatments were to have region-specific effects.
Metal ions and flexibility in a viral RNA pseudoknot at atomic resolution
Authors: Egli Martin , Minasov George , Su Li , Rich Alexander
Published: July 2002

Many pathogenic viruses use programmed −1 ribosomal frameshifting to regulate translation of their structural and enzymatic proteins from polycistronic mRNAs. Frameshifting is commonly stimulated by a pseudoknot located downstream from a slippery sequence, the latter positioned at the ribosomal A and P sites. We report here the structures of two crystal forms of the frameshifting RNA pseudoknot from beet western yellow virus at resolutions of 1.25 and 2.85 Å. Because of the very high resolution of 1.25 Å, ten mono- and divalent metal ions per asymmetric unit could be identified, giving insight into potential roles of metal ions in stabilizing the pseudoknot. A magnesium ion located at the junction of the two pseudoknot stems appears to play a crucial role in stabilizing the structure. Because the two crystal forms exhibit mostly unrelated packing interactions and local crystallographic disorder in the high-resolution form was resolvable, the two structures offer the most detailed view yet of the conformational preference and flexibility of an RNA pseudoknot.
Modulation of protein translation by Nck-1
Authors: Kebache Sem , Zuo Dongmei , Chevet Eric , Larose Louise
Published: July 2002

In mammals, Nck represented by two genes, is a 47-kDa SH2/SH3 domain-containing protein lacking intrinsic enzymatic function. Here, we reported that the first and the third SH3 domains of Nck-1 interact with the C-terminal region of the β subunit of the eukaryotic initiation factor 2 (eIF2β). Binding of eIF2β was specific to the SH3 domains of Nck-1, and
in vivo
, the interaction Nck/eIF2β was demonstrated by reciprocal coimmunoprecipitations. In addition, Nck was detected in a molecular complex with eIF2β in an enriched ribosomal fraction, whereas no other SH2/SH3 domain-containing adapters were found. Cell fractionation studies demonstrated that the presence of Nck in purified ribosomal fractions was enhanced after insulin stimulation, suggesting that growth factors dynamically regulate translocation of Nck to ribosomes. In HEK293 cells, we observed that transient overexpression of Nck-1 significantly enhanced Cap-dependent and -independent protein translation. This effect of Nck-1 required the integrity of its first and third SH3 domains originally found to interact with eIF2β. Finally,
in vitro
, Nck-1 also increased protein translation, revealing a direct role for Nck-1 in this process. Our study demonstrates that in addition to mediate receptor tyrosine kinase signaling, Nck-1 modulates protein translation potentially through its direct interaction with an intrinsic component of the protein translation machinery.
Formation of oriented molecular nanowires on mica surface
Authors: Akutagawa Tomoyuki , Ohta Takanori , Hasegawa Tatsuo , Nakamura Takayoshi , Christensen Christian A. , Becher Jan
Published: July 2002

Molecular “nanowire” structures composed of the charge transfer complex of a bis-tetrathiafulvalene substituted macrocycle and tetrafluorotetracyanoquinodimethane were constructed on mica substrates by employing the Langmuir–Blodgett technique. The nanowires transferred from a dilute aqueous potassium chloride subphase had typical dimensions of 2.5 nm × 50 nm × 1 μm. The nanowires are oriented to specific directions, corresponding to the directions of the potassium-ion array on the mica surface having sixfold symmetry. Such correlation between the nanowires and the substrate surface was also observed when a dilute aqueous rubidium chloride subphase was used. On the other hand, the correlation completely disappeared when the subphase contained divalent cations, indicating that the molecular nanowires orient by recognizing the monocation array on the mica surface. The nanowires formed by the vertical dipping method coexist with the monolayers. Only nanowire structures are, however, observed when we apply the horizontal lifting method. Based on the crystal structure of a related complex, a possible structure of the nanowires is presented. The conductivity of the nanowires was estimated to be of the order of 10
−3
S⋅cm
−1
. The nanowires formed specific (regular) structures such as T-shape junctions, suggesting their use in construction of future molecular nanoscale devices.
Corticotropin-releasing hormone: An autocrine hormone that promotes lipogenesis in human sebocytes
Authors: Zouboulis Christos C. , Seltmann Holger , Hiroi Naoki , Chen WenChieh , Young Maggie , Oeff Marina , Scherbaum Werner A. , Orfanos Constantin E. , McCann Samuel M. , Bornstein Stefan R.
Published: July 2002

Sebaceous glands may be involved in a pathway conceptually similar to that of the hypothalamic-pituitary-adrenal (HPA) axis. Such a pathway has been described and may occur in human skin and lately in the sebaceous glands because they express neuropeptide receptors. Corticotropin-releasing hormone (CRH) is the most proximal element of the HPA axis, and it acts as central coordinator for neuroendocrine and behavioral responses to stress. To further examine the probability of an HPA equivalent pathway, we investigated the expression of CRH, CRH-binding protein (CRH-BP), and CRH receptors (CRH-R) in SZ95 sebocytes
in vitro
and their regulation by CRH and several other hormones. CRH, CRH-BP, CRH-R1, and CRH-R2 were detectable in SZ95 sebocytes at the mRNA and protein levels: CRH-R1 was the predominant type (CRH-R1/CRH-R2 = 2). CRH was biologically active on human sebocytes: it induced biphasic increase in synthesis of sebaceous lipids with a maximum stimulation at 10
−7
M and up-regulated mRNA levels of 3β- hydroxysteroid dehydrogenase/Δ
5–4
isomerase, although it did not affect cell viability, cell proliferation, or IL-1β-induced IL-8 release. CRH, dehydroepiandrosterone, and 17β-estradiol did not modulate CRH-R expression, whereas testosterone at 10
−7
M down-regulated CRH-R1 and CRH-R2 mRNA expression at 6 to 24 h, and growth hormone (GH) switched CRH-R1 mRNA expression to CRH-R2 at 24 h. Based on these findings, CRH may be an autocrine hormone for human sebocytes that exerts homeostatic lipogenic activity, whereas testosterone and growth hormone induce CRH negative feedback. The findings implicate CRH in the clinical development of acne, seborrhea, androgenetic alopecia, skin aging, xerosis, and other skin disorders associated with alterations in lipid formation of sebaceous origin.
Diazepam-induced changes in sleep: Role of the α1 GABAAreceptor subtype
Authors: Tobler Irene , Kopp Caroline , Deboer Tom , Rudolph Uwe
Published: July 2002

Ligands acting at the benzodiazepine (BZ) site of γ-aminobutyric acid type A (GABAA) receptors currently are the most widely used hypnotics. BZs such as diazepam (Dz) potentiate GABAAreceptor activation. To determine the GABAAreceptor subtypes that mediate the hypnotic action of Dz wild-type mice and mice that harbor Dz-insensitive α1 GABAAreceptors [α1 (H101R) mice] were compared. Sleep latency and the amount of sleep after Dz treatment were not affected by the point mutation. An initial reduction of rapid eye movement (REM) sleep also occurred equally in both genotypes. Furthermore, the Dz-induced changes in the sleep and waking electroencephalogram (EEG) spectra, the increase in power density above 21 Hz in non-REM sleep and waking, and the suppression of slow-wave activity (SWA; EEG power in the 0.75- to 4.0-Hz band) in non-REM sleep were present in both genotypes. Surprisingly, these effects were even more pronounced in α1(H101R) mice and sleep continuity was enhanced by Dz only in the mutants. Interestingly, Dz did not affect the initial surge of SWA at the transitions to sleep, indicating that the SWA-generating mechanisms are not impaired by the BZ. We conclude that the REM sleep inhibiting action of Dz and its effect on the EEG spectra in sleep and waking are mediated by GABAAreceptors other than α1, i.e., α2, α3, or α5 GABAAreceptors. Because α1 GABAAreceptors mediate the sedative action of Dz, our results provide evidence that the hypnotic effect of Dz and its EEG “fingerprint” can be dissociated from its sedative action.
Molecular characterization of antibody specificities against myelin/oligodendrocyte glycoprotein in autoimmune demyelination
Authors: von Büdingen Hans-Christian , Hauser Stephen L. , Fuhrmann Antje , Nabavi Cameron B. , Lee Joy I. , Genain Claude P.
Published: July 2002

Myelin/oligodendrocyte glycoprotein (MOG) is a target antigen for myelin-destructive Abs in autoimmune central nervous system demyelinating disorders. Little is known about the molecular and structural basis of these pathogenic Ab responses. Here, we have characterized anti-MOG Ab specificities in the marmoset model of experimental allergic encephalomyelitis, by means of a combinatorial IgG-Fab library. We found that a diverse population of Ig genes encodes for auto-Abs that exclusively recognize conformation-dependent antigenic targets on MOG. These antigenic domains correspond to exposed epitopesin vivo, as the Fab fragments recognize native MOGin situin marmoset brain tissue. The Ab fragments described here represent Ab specificities that are common constituents of the humoral immune repertoire against MOG in outbred populations, as demonstrated by their ability to displace native anti-MOG Abs present in sera from MOG-immune marmosets and patients with multiple sclerosis. Furthermore, neuropathological analysis and characterization of Ab epitope specificities in animals immunized with MOG or MOG-derived peptides revealed that only conformation-dependent Abs are associated with demyelinating activity, suggesting that epitope recognition is an important factor for Ab pathogenicity. Our findings provide novel and unexpected knowledge on the diversity of anti-MOG Ab responses in nonhuman primates and humans, and will permit the dissection of pathogenic auto-Ab properties in multiple sclerosis.
Functional neuroanatomy of biological motion perception in humans
Authors: Vaina Lucia M. , Solomon Jeffrey , Chowdhury Sanjida , Sinha Pawan , Belliveau John W.
Published: July 2002

We used whole brain functional MRI to investigate the neural
network specifically engaged in the recognition of “biological
motion” defined by point-lights attached to the major joints and
head of a human walker. To examine the specificity of brain regions
responsive to biological motion, brain activations obtained during a
“walker vs. non-walker” discrimination task were compared with
those elicited by two other tasks: (
i
) non-rigid motion
(NRM), involving the discrimination of overall motion direction in the
same “point-lights” display, and (
ii
) face-gender
discrimination, involving the discrimination of gender in briefly
presented photographs of men and women. Brain activity specific to
“biological motion” recognition arose in the lateral cerebellum
and in a region in the lateral occipital cortex presumably
corresponding to the area KO previously shown to be particularly
sensitive to kinetic contours. Additional areas significantly activated
during the biological motion recognition task involved both, dorsal and
ventral extrastriate cortical regions. In the ventral regions both
face-gender discrimination and biological motion recognition elicited
activation in the lingual and fusiform gyri and in the Brodmann areas
22 and 38 in superior temporal sulcus (STS). Along the dorsal pathway,
both biological motion recognition and non-rigid direction
discrimination gave rise to strong responses in several known motion
sensitive areas. These included Brodmann areas 19/37, the inferior
(Brodmann Area 39), and superior parietal lobule (Brodmann Area 7).
Thus, we conjecture that, whereas face (and form) stimuli activate
primarily the ventral system and motion stimuli primarily the dorsal
system, recognition of biological motion stimuli may activate both
systems as well as their confluence in STS. This hypothesis is
consistent with our findings in stroke patients, with unilateral brain
lesions involving at least one of these areas, who, although correctly
reporting the direction of the point-light walker, fail on the
biological motion task.
Early postnatal ataxia and abnormal cerebellar development in mice lacking Xeroderma pigmentosum Group A and Cockayne Syndrome Group B DNA repair genes
Authors: Murai Machiko , Enokido Yasushi , Inamura Naoko , Yoshino Masafumi , Nakatsu Yoshimichi , van der Horst Gijsbertus T. J. , Hoeijmakers Jan H. J. , Tanaka Kiyoji , Hatanaka Hiroshi
Published: July 2002

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are rare autosomal recessive disorders associated with a defect in the nucleotide excision repair (NER) pathway required for the removal of DNA damage induced by UV light and distorting chemical adducts. Although progressive neurological dysfunction is one of the hallmarks of CS and of some groups of XP patients, the causative mechanisms are largely unknown. Here we show that mice lacking both the
XPA
(XP-group A) and
CSB
(CS-group B) genes in contrast to the single mutants display severe growth retardation, ataxia, and motor dysfunction during early postnatal development. Their cerebella are hypoplastic and showed impaired foliation and stunted Purkinje cell dendrites. Reduced neurogenesis and increased apoptotic cell death occur in the cerebellar external granular layer. These findings suggest that
XPA
and
CSB
have additive roles in the mouse nervous system and support a crucial role for these genes in normal brain development.
Selective blockade of T lymphocyte K+channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis
Authors: Beeton Christine , Wulff Heike , Barbaria Jocelyne , Clot-Faybesse Olivier , Pennington Michael , Bernard Dominique , Cahalan Michael D. , Chandy K. George , Béraud Evelyne
Published: July 2002

Adoptive transfer experimental autoimmune encephalomyelitis (AT-EAE), a disease resembling multiple sclerosis, is induced in rats by myelin basic protein (MBP)-activated CD4+T lymphocytes. By patch-clamp analysis, encephalitogenic rat T cells stimulated repeatedlyin vitroexpressed a unique channel phenotype (“chronically activated”) with large numbers of Kv1.3 voltage-gated channels (≈1500 per cell) and small numbers of IKCa1 Ca2+-activated K+channels (≈50–120 per cell). In contrast, resting T cells displayed 0–10 Kv1.3 and 10–20 IKCa1 channels per cell (“quiescent” phenotype), whereas T cells stimulated once or twice expressed ≈200 Kv1.3 and ≈350 IKCa1 channels per cell (“acutely activated” phenotype). Consistent with their channel phenotype, [3H]thymidine incorporation by MBP-stimulated chronically activated T cells was suppressed by the peptide ShK, a blocker of Kv1.3 and IKCa1, and by an analog (ShK-Dap22) engineered to be highly specific for Kv1.3, but not by a selective IKCa1 blocker (TRAM-34). The combination of ShK-Dap22and TRAM-34 enhanced the suppression of MBP-stimulated T cell proliferation. Based on thesein vitroresults, we assessed the efficacy of K+channel blockers in AT-EAE. Specific and simultaneous blockade of the T cell channels by ShK or by a combination of ShK-Dap22plus TRAM-34 prevented lethal AT-EAE. Blockade of Kv1.3 alone with ShK-Dap22, but not of IKCa1 with TRAM-34, was also effective. When administered after the onset of symptoms, ShK or the combination of ShK-Dap22plus TRAM-34 greatly ameliorated the clinical course of both moderate and severe AT-EAE. We conclude that selective targeting of Kv1.3, alone or with IKCa1, may provide an effective new mode of therapy for multiple sclerosis.
Helicobacter pylori
genetic diversity within the gastric niche of a single human host
Authors: Israel Dawn A. , Salama Nina , Krishna Uma , Rieger Ulrich M. , Atherton John C. , Falkow Stanley , Peek Richard M.
Published: July 2002

Isolates of the gastric pathogen
Helicobacter pylori
harvested from different individuals are highly polymorphic.
Strain variation also has been observed within a single host. To more
fully ascertain the extent of
H. pylori
genetic
diversity within the ecological niche of its natural host, we harvested
additional isolates of the sequenced
H. pylori
strain
J99 from its human source patient after a 6-year interval. Randomly
amplified polymorphic DNA PCR and DNA sequencing of four unlinked loci
indicated that these isolates were closely related to the original
strain. In contrast, microarray analysis revealed differences in
genetic content among all of the isolates that were not detected by
randomly amplified polymorphic DNA PCR or sequence analysis.
Several ORFs from loci scattered throughout the chromosome in the
archival strain did not hybridize with DNA from the recent strains,
including multiple ORFs within the J99 plasticity zone. In addition,
DNA from the recent isolates hybridized with probes for ORFs specific
for the other fully sequenced
H. pylori
strain 26695,
including a putative
traG
homolog. Among the additional
J99 isolates, patterns of genetic diversity were distinct both when
compared with each other and to the original prototype isolate. These
results indicate that within an apparently homogeneous population, as
determined by macroscale comparison and nucleotide sequence analysis,
remarkable genetic differences exist among single-colony isolates of
H. pylori
. Direct evidence that
H. pylori
has the capacity to lose and possibly acquire exogenous DNA is
consistent with a model of continuous microevolution within its cognate
host.
Circular RNAs from transcripts of the rat cytochrome P450 2C24 gene: correlation with exon skipping.
Authors: Zaphiropoulos P G
Published: July 2002

The cytochrome P450 2C24 gene is characterized by the capability to generate, in rat kidney, a transcript containing exons 2 and 4 spliced at correct sites but having the donor site of exon 4 directly joined to the acceptor site of exon 2 (exon scrambling). By reverse transcriptase-PCR analysis, it is now shown that the only exons present in the scrambled transcript are exons 2, 3, and 4 and that this molecule lacks a poly(A)+ tail. Furthermore, the use of PCR primers in both orientations of either exon 2 or exon 4 revealed that the orders of the exons in the scrambled transcript are 2-3-4-2 and 4-2-3-4, respectively. These results, combined with the observation that P450 2C24 is a single-copy gene, with no duplication of the exon 2 to exon 4 segment, suggest that the scrambled transcript has properties consistent with that of a circular molecule. In line with this is the observation of an increased resistance of the transcript to phosphodiesterase I, a 3'-exonuclease. Moreover, an alternatively processed cytochrome P450 2C24 mRNA, lacking the three scrambled exons and having exon 1 directly joined to exon 5, has been identified in kidney and liver, tissues that express the scrambled transcript. This complete identity of the exons that are absent in the alternatively processed mRNA but present in the scrambled transcript is interpreted as indicative of the possibility that exon scrambling and exon skipping might be interrelated phenomena. It is therefore proposed that alternative pre-mRNA processing has the potential to generate not only mRNAs lacking one or more exons but also circular RNA molecules.
1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis.
Authors: Cantorna M T , Hayes C E , DeLuca H F
Published: July 2002

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease believed to be a model for the human disease multiple sclerosis (MS). Induced by immunizing B10.PL mice with myelin basic protein (MBP), EAE was completely prevented by the administration of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. 1,25-(OH)2D3 could also prevent the progression of EAE when administered at the appearance of the first disability symptoms. Withdrawal of 1,25-(OH)2D3 resulted in a resumption of the progression of EAE. Thus, the block by 1,25-(OH)2D3 is reversible. A deficiency of vitamin D resulted in an increased susceptibility to EAE. Thus, 1,25-(OH)2D3 or its analogs are potentially important for treatment of MS.
Sexual orientation in Drosophila is altered by the satori mutation in the sex-determination gene fruitless that encodes a zinc finger protein with a BTB domain.
Authors: Ito H , Fujitani K , Usui K , Shimizu-Nishikawa K , Tanaka S , Yamamoto D
Published: July 2002

We have isolated a new Drosophila mutant, satori (sat), the males of which do not court or copulate with female flies. The sat mutation comaps with fruitless (fru) at 91B and does not rescue the bisexual phenotype of fru, indicating that sat is allelic to fru (fru(sat)). The fru(sat) adult males lack a male-specific muscle, the muscle of Lawrence, as do adult males with other fru alleles. Molecular cloning and analyses of the genomic and complementary DNAs indicated that transcription of the fru locus yields several different transcripts. The sequence of fru cDNA clones revealed a long open reading frame that potentially encodes a putative transcription regulator with a BTB domain and two zinc finger motifs. In the 5' noncoding region, three putative transformer binding sites were identified in the female transcript but not in male transcripts. The fru gene is expressed in a population of brain cells, including those in the antennal lobe, that have been suggested to be involved in determination of male sexual orientation. We suggest that fru functions downstream of tra in the sex-determination cascade in some neural cells and that inappropriate sexual development of these cells in the fru mutants results in altered sexual orientation of the fly.
Motion perception: seeing and deciding.
Authors: Shadlen M N , Newsome W T
Published: July 2002

The primate visual system offers unprecedented opportunities for investigating the neural basis of cognition. Even the simplest visual discrimination task requires processing of sensory signals, formation of a decision, and orchestration of a motor response. With our extensive knowledge of the primate visual and oculomotor systems as a base, it is now possible to investigate the neural basis of simple visual decisions that link sensation to action. Here we describe an initial study of neural responses in the lateral intraparietal area (LIP) of the cerebral cortex while alert monkeys discriminated the direction of motion in a visual display. A subset of LIP neurons carried high-level signals that may comprise a neural correlate of the decision process in our task. These signals are neither sensory nor motor in the strictest sense; rather they appear to reflect integration of sensory signals toward a decision appropriate for guiding movement. If this ultimately proves to be the case, several fascinating issues in cognitive neuroscience will be brought under rigorous physiological scrutiny.
Random phage mimotopes recognized by monoclonal antibodies against the pyruvate dehydrogenase complex-E2 (PDC-E2).
Authors: Cha S , Leung P S , Van de Water J , Tsuneyama K , Joplin R E , Ansari A A , Nakanuma Y , Schatz P J , Cwirla S , Fabris L E , Neuberger J M , Gershwin M E , Coppel R L
Published: July 2002

Dihydrolipoamide acetyltransferase, the E2 component of the pyruvate dehydrogenase complex (PDC-E2), is the autoantigen most commonly recognized by autoantibodies in primary biliary cirrhosis (PBC). We identified a peptide mimotope(s) of PDC-E2 by screening a phage-epitope library expressing random dodecapeptides in the pIII coat protein of fd phage using C355.1, a murine monoclonal antibody (mAb) that recognizes a conformation-dependent epitope in the inner lipoyl domain of PDC-E2 and uniquely stains the apical region of bile duct epithelium (BDE) only in patients with PBC. Eight different sequences were identified in 36 phage clones. WMSYPDRTLRTS was present in 29 clones; WESYPFRVGTSL, APKTYVSVSGMV, LTYVSLQGRQGH, LDYVPLKHRHRH, AALWGVKVRHVS, KVLNRIMAGVRH and GNVALVSSRVNA were singly represented. Three common amino acid motifs (W-SYP, TYVS, and VRH) were shared among all peptide sequences. Competitive inhibition of the immunohistochemical staining of PBC BDE was performed by incubating the peptides WMSYPDRTLRTS, WESYPDRTLRTS, APKTYVSVSGMV, and AALWGVKVRHVS with either C355.1 or a second PDC-E2-specific mAb, C150.1. Both mAbs were originally generated to PDC-E2 but map to distinct regions of PDC-E2. Two of the peptides, although selected by reaction with C355.1, strongly inhibited the staining of BDE by C150.1, whereas the peptide APKTYVSVSGMV consistently inhibited the staining of C355.1 on biliary duct epithelium more strongly than the typical mitochondrial staining of hepatocytes. Rabbit sera raised against the peptide WMSYPDRTLRTS stained BDE of livers and isolated bile duct epithelial cells of PBC patients more intensively than controls. The rabbit sera stained all size ducts in normals, but only small/medium-sized ductules in PBC livers. These studies provide evidence that the antigen present in BDE is a molecular mimic of PDC-E2, and not PDC-E2 itself.
Identification of a functionally important sequence in the cytoplasmic tail of integrin beta 3 by using cell-permeable peptide analogs.
Authors: Liu K Y , Timmons S , Lin Y Z , Hawiger J
Published: July 2002

Integrins are major two-way signaling receptors responsible for the attachment of cells to the extracellular matrix and for cell-cell interactions that underlie immune responses, tumor metastasis, and progression of atherosclerosis and thrombosis. We report the structure-function analysis of the cytoplasmic tail of integrin beta 3 (glycoprotein IIla) based on the cellular import of synthetic peptide analogs of this region. Among the four overlapping cell-permeable peptides, only the peptide carrying residues 747-762 of the carboxyl-terminal segment of integrin beta 3 inhibited adhesion of human erythroleukemia (HEL) cells and of human endothelial cells (ECV) 304 to immobilized fibrinogen mediated by integrin beta 3 heterodimers, alpha IIb beta 3, and alpha v beta 3, respectively. Inhibition of adhesion was integrin-specific because the cell-permeable beta 3 peptide (residues 747-762) did not inhibit adhesion of human fibroblasts mediated by integrin beta 1 heterodimers. Conversely, a cell-permeable peptide representing homologous portion of the integrin beta 1 cytoplasmic tail (residues 788-803) inhibited adhesion of human fibroblasts, whereas it was without effect on adhesion of HEL or ECV 304 cells. The cell-permeable integrin beta 3 peptide (residues 747-762) carrying a known loss-of-function mutation (Ser752Pro) responsible for the genetic disorder Glanzmann thrombasthenia Paris I did not inhibit cell adhesion of HEL or ECV 304 cells, whereas the beta 3 peptide carrying a Ser752Ala mutation was inhibitory. Although Ser752 is not essential, Tyr747 and Tyr759 form a functionally active tandem because conservative mutations Tyr747Phe or Tyr759Phe resulted in a nonfunctional cell permeable integrin beta 3 peptide. We propose that the carboxyl-terminal segment of the integrin beta 3 cytoplasmic tail spanning residues 747-762 constitutes a major intracellular cell adhesion regulatory domain (CARD) that modulates the interaction of integrin beta 3-expressing cells with immobilized fibrinogen. Import of cell-permeable peptides carrying this domain results in inhibition "from within" of the adhesive function of these integrins.
In vivo tracking of platelets: circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function.
Authors: Michelson A D , Barnard M R , Hechtman H B , MacGregor H , Connolly R J , Loscalzo J , Valeri C R
Published: July 2002

To examine the hypothesis that surface P-selectin-positive (degranulated) platelets are rapidly cleared from the circulation, we developed novel methods for tracking of platelets and measurement of platelet function in vivo. Washed platelets prepared from nonhuman primates (baboons) were labeled with PKH2 (a lipophilic fluorescent dye), thrombin-activated, washed, and reinfused into the same baboons. Three-color whole blood flow cytometry was used to simultaneously (i) identify platelets with a mAb directed against glycoprotein (GP)IIb-IIIa (integrin alpha 11b beta 3), (ii) distinguish infused platelets by their PKH2 fluorescence, and (iii) analyze platelet function with mAbs. Two hours after infusion of autologous thrombin-activated platelets (P-selectin-positive, PKH2-labeled), 95 +/- 1% (mean +/- SEM, n = 5) of the circulating PKH2-labeled platelets had become P-selectin-negative. Compared with platelets not activated with thrombin preinfusion, the recovery of these circulating PKH2-labeled, P-selectin-negative platelets was similar 24 h after infusion and only slightly less 48 h after infusion. The loss of platelet surface P-selectin was fully accounted for by a 67.1 +/- 16.7 ng/ml increase in the plasma concentration of soluble P-selectin. The circulating PKH2-labeled, P-selectin-negative platelets were still able to function in vivo, as determined by their (i) participation in platelet aggregates emerging from a bleeding time wound, (ii) binding to Dacron in an arteriovenous shunt, (iii) binding of mAb PAC1 (directed against the fibrinogen binding site on GPIIb-IIIa), and (iv) generation of procoagulant platelet-derived microparticles. In summary, (i) circulating degranulated platelets rapidly lose surface P-selectin to the plasma pool, but continue to circulate and function; and (ii) we have developed novel three-color whole blood flow cytometric methods for tracking of platelets and measurement of platelet function in vivo.