bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical characterization of polychromatic organic light emitting diodes
Authors: Troadec David , Moliton André , Ratier Bernard , Antony Rémy , Hiorns Roger C.
Published: January 2005

Luminance and quantum yields of organic light emitting diodes (OLEDs) are generally calculated by using a hypothetic monochromatic emission even though the actual external emission is lower than the internal emission because of internal reflection, and is polychromatic. For organic materials, we present the effects of the total internal reflection on quantum yields. Calculations for the luminance and the efficiency of an ideal pseudomonochromatic source are compared with those for a real polychromatic source. While we demonstrate that the calculation of the yield is practically unchanged whatever hypothesis is used, we do show, however, that by assuming that the source is pseudomonochromatic, the luminances of green and blue OLEDs are overvalued or undervalued by a factor of 4, respectively.
Low-temperature copper-induced lateral growth of polycrystalline germanium assisted by external compressive stress
Authors: Hekmatshoar Bahman , Mohajerzadeh Shams , Shahrjerdi Davood , Afzali-Kusha Ali , Robertson Michael D. , Tonita Aaryn
Published: January 2005

Copper-induced lateral growth of polycrystalline germanium (poly-Ge) at temperatures as low as 150°C was enabled by the application of an external mechanical stress during the annealing step of sample processing. An equivalent compressive strain of 0.05% was externally applied at 150°C for 10h to a deposited amorphous Ge layer and crystalline growth rates of 2.5 and 1.8μm∕h were observed in directions parallel and perpendicular to the stress axis, respectively. These results were confirmed by scanning electron microscope and transmission electron microscopy (TEM) analyses. In addition, TEM and x-ray diffraction analyses indicate that a fraction of poly-Ge annealed in the presence of applied compressive stress possessed a tetragonal structure with space-group P43212. The presence of the tetragonal phase is hypothesized to be the primary mechanism responsible for the lateral growth of poly-Ge.
Propagator corrections to adiabatic time-dependent density-functional theory linear response theory
Authors: Casida Mark E.
Published: January 2005

It has long been known that only one-electron excitations are available from adiabatic time-dependent density functional theory (TDDFT). This is particularly clear in Casida’s formulation of TDDFT linear response theory [M. E. Casida, in Recent Advances in Density Functional Methods, Part I, edited by D. P. Chong (World Scientific, Singapore, 1995), p. 155]. Nevertheless the explicit inclusion of two- and higher-electron excitations is necessary for an adequate description of some excited states, notably the first excited singlet states of butadiene and quartet excited states of molecules with a doublet ground state. The equation-of-motion superoperator approach is used here to derive a Casida-like propagator equation which can be clearly separated into an adiabatic part and a nonadiabatic part. The adiabatic part is identified as corresponding to Casida’s equation for adiabatic TDDFT linear response theory. This equivalence is confirmed by deriving a general formula which includes the result that Gonze and Scheffler derived to show the equivalence of TDDFT and Görling-Levy adiabatic connection perturbation theory for the exchange-only optimized effective potential [X. Gonze and M. Scheffler, Phys. Rev. Lett. 82, 4416 (1999)]. The nonadiabatic part explicitly corrects adiabatic TDDFT for two- and higher-electron excitations. The “dressed TDDFT” of Maitra, Zhang, Cave, and Burke is obtained as a special case where the ground state is closed shell [N. T. Maitra, F. Zhang, R. J. Cave, and K. Burke, J. Chem. Phys. 120, 5932 (2004)]. The extension of dressed TDDFT to the case where the ground state is an open-shell doublet is presented, highlighting the importance of correctly accounting for symmetry in this theory. The extension to other ground state spin symmetries is a straightforward consequence of the present work.
Targeted Car–Parrinello molecular dynamics: Elucidating double proton transfer in formic acid dimer
Authors: Markwick Phineus R. L. , Doltsinis Nikos L. , Marx Dominik
Published: January 2005

The targeted molecular dynamics method, making possible the study of rare events, has been assessed in the framework of Car–Parrinello ab initio molecular dynamics. As a test case, we have studied the staggered–eclipsed rotation of ethane. The technique has subsequently been applied to investigate the nature of double proton transfer in formic acid dimer. The latter is found to follow a concerted transfer mechanism involving an essentially planar transition state. A “funnel-like region” of the potential energy surface is identified, where floppy intermolecular modes stiffen upon approaching the transition state.
Spatial homogeneity of optically switched semiconductor photonic crystals and of bulk semiconductors
Authors: Euser Tijmen G. , Vos Willem L.
Published: January 2005

In this paper we discuss free carrier generation by pulsed laser fields as a mechanism to switch the optical properties of semiconductor photonic crystals and bulk semiconductors on an ultrafast time scale. Requirements are set for the switching magnitude, the time-scale, the induced absorption, as well as the spatial homogeneity, in particular for silicon at λ=1550nm. Using a nonlinear absorption model, we calculate carrier depth profiles and define a homogeneity length lhom. Homogeneity length contours are visualized in a plane spanned by the linear and two-photon absorption coefficients. Such a generalized homogeneity plot allows us to find optimum switching conditions at pump frequencies near ν∕c=5000cm−1 (λ=2000nm). We discuss the effect of scattering in photonic crystals on the homogeneity. We experimentally demonstrate a 10% refractive index switch in bulk silicon within 230fs with a lateral homogeneity of more than 30μm. Our results are relevant for switching of modulators in the absence of photonic crystals.
High Q factor bonding using natural resin for reduced thermal noise of test masses
Authors: Schediwy S. W. , Gras S. , Ju L. , Blair D. G.
Published: January 2005

We show that a low acoustic loss resin enables composite mechanical structures to be bonded with minimal Q degradation. The resin is excreted from the Australian native grass tree Xanthorrhoea. This resin has traditionally been used as an adhesive by the Australian Aborigines. It is shown that the Q factor of the resin is greater than 300 for the 5180Hz resonance, which allows a high Q factor niobium resonator to be constructed with bonded mirrors while maintaining a Q of ∼106.
Interaction of wide-band-gap single crystals with 248-nm excimer laser radiation. XI. The effect of water vapor and temperature on laser desorption of neutral atoms from sodium chloride
Authors: Nwe K. H. , Langford S. C. , Dickinson J. T. , Hess W. P.
Published: January 2005

We show that low partial pressures of water vapor (10−5Pa) dramatically increase the intensity of neutral Na and Cl emissions from cleaved, single-crystal NaCl during pulsed laser irradiation at 248 nm (KrF excimer). The time-of-flight distributions of these emissions are consistent with thermal desorption from laser-heated surfaces. Significantly, introducing water vapor lowers the particle velocities and thus the effective surface temperature during emission. Transmission measurements confirm that laser absorption is reduced in the presence of water vapor. The Arrhenius analysis of the emission intensities and effective temperatures show reduced activation energies in the presence of water vapor, which more than compensate for the vapor-induced reduction in laser absorption and surface temperature. Atomic force and scanning electron microscopy of the irradiated surfaces show evidence for accelerated monolayer-scale erosion in the presence of water vapor. A mechanism for the effect of water on these emission and erosion processes is proposed and discussed.
Characterization of helium discharge cleaning plasmas in ADITYA tokamak using collisional-radiative model code
Authors: Prakash Ram , Vasu P. , Kumar Vinay , Manchanda R. , Chowdhuri M. B. , Goto M.
Published: January 2005

The wall conditioning of the ADITYA tokamak is usually done, by first producing an electron cyclotron resonance (ECR) plasma inside the vessel and then superimposing a pulsed ohmic discharge on the ECR background. Sometimes, helium gas is used as a working gas. In this article, the spectral line emissions of neutral helium for the two different plasmas—namely, the ECR and the pulsed discharge cleaning (PDC) plasmas—have been analyzed using a collisional-radiative (CR)-model code to estimate the electron density and temperature. We are able to match the experimentally obtained relative intensity ratios with those predicted by the model under the assumption of ionizing plasma condition if the possible effects of the metastable states are not ignored. This has been done by using the populations of two metastable levels (2S1 and 2S3) as independent parameters in addition to the ground states of neutrals and ions in the CR model under a quasisteady-state approximation. It is further seen that, it is the metastables and not the recombination (including dielectronic) processes that lead to a better fit with experimental observations. The column density of neutrals inferred from this analysis implies that the emission from the PDC discharge emanates from a large region of the vessel, while in the ECR discharge, the plasma responsible for the emission is restricted to a narrow region. This is also borne out by experimental observation.
Thermoelastic effects as a way of creating transient renewable reflective optics
Authors: Ryutov D. D.
Published: January 2005

A technique for creating renewable reflective optics suitable for focusing of pulsed laser beams is proposed. It is based on the heating of the surface of a planar reflecting slab by an auxiliary heating source that causes thermal expansion of the slab material and creates a desired surface relief, e.g., a focusing mirror. The presence of this relief is a transient phenomenon, but, for a short-enough main pulse, this does not cause any problems. If the surface is damaged by the main pulse, the shifting of the slab and repeating the whole cycle allows recreating the transient mirror. Favorable features of this approach include controlling the optics “at a distance,” without any direct mechanical contact. A detailed discussion of the possibilities provided by this technique for the focusing of x-ray beams at the planned Linac Coherent Light Source facility at Stanford is presented. It is concluded that a 20-fold increase of intensity of an 8 keV beam and 100-fold increase of intensity of a 0.8 keV beam is possible. A set of design equations and constraints is formulated. The analysis presented can be used as a template for analyses of similar transient optical systems for the UV and optical range.
A New Two-Armed Colorimetric Chemosensor for Fluoride
Authors: Wu Jin-Long , He Yong-Bing , Wei Lan-Hua , Meng Ling-Zhi , Yang Ting-Xian , Liu Xin
Published: January 2005

The neutral anion receptor 1 was synthesized by an easy method with high yield. The binding properties of anions with 1 were examined by UV-vis and 1H NMR spectroscopy. Receptor 1 can form a 1 : 2 complex with F−, and 1 : 1 complexes with AcO− and H2PO4− anions, respectively, by multiple hydrogen-bonding interactions. There is an observable colour change for the complex formed by 1 and F−.
In vivomodulation of morphogenetic movements inDrosophilaembryos with femtosecond laser pulses
Authors: Supatto Willy , Débarre Delphine , Moulia Bruno , Brouzés Eric , Martin Jean-Louis , Farge Emmanuel , Beaurepaire Emmanuel
Published: January 2005

The complex biomechanical events associated with embryo development are investigatedin vivo, by using femtosecond laser pulse-induced ablation combined with multimodal nonlinear microscopy. We demonstrate controlled intravital ablations preserving local cytoskeleton dynamics and resulting in the modulation of specific morphogenetic movements in nonmutantDrosophilaembryos. A quantitative description of complex movements is obtained both in GFP-expressing systems by using whole-embryo two-photon microscopy and in unlabeled nontransgenic embryos by using third harmonic generation microscopy. This methodology provides insight into the issue of mechano-sensitive gene expression by revealing the correlation ofin vivotissue deformation patterns with Twist protein expression in stomodeal cells at gastrulation.
EsxA and EsxB are secreted by an ESAT-6-like system that is required for the pathogenesis ofStaphylococcus aureusinfections
Authors: Burts Monica L. , Williams Wade A. , DeBord Kristin , Missiakas Dominique M.
Published: January 2005

Mycobacterium tuberculosissecretes ESAT-6, a virulence factor that triggers cell-mediated immune responses and IFN-γ production during tuberculosis. ESAT-6 is transported across the bacterial envelope by a specialized secretion system with a FSD (FtsK-SpoIIIEdomain) membrane protein. Although the presence of ESAT-6-like genes has been identified in the genomes of other microbes, the possibility that they may encode general virulence functions has hitherto not been addressed. Herein we show that the human pathogenStaphylococcus aureussecretes EsxA and EsxB, ESAT-6-like proteins, across the bacterial envelope. StaphylococcalesxAandesxBare clustered with six other genes and some of these are required for synthesis or secretion of EsxA and EsxB. Mutants that failed to secrete EsxA and EsxB displayed defects in the pathogenesis ofS. aureusmurine abscesses, suggesting that this specialized secretion system may be a general strategy of human bacterial pathogenesis.
Metabolizing enzyme toxicology assay chip (MetaChip) for high-throughput microscale toxicity analyses
Authors: Lee Moo-Yeal , Park Chan Beum , Dordick Jonathan S. , Clark Douglas S.
Published: January 2005

The clinical progression of new chemical entities to pharmaceuticals remains hindered by the relatively slow pace of technology development in toxicology and clinical safety evaluation, particularly
in vitro
approaches, that can be used in the preclinical and early clinical phases of drug development. To alleviate this bottle-neck, we have developed a metabolizing enzyme toxicology assay chip (MetaChip) that combines high-throughput P450 catalysis with cell-based screening on a microscale platform. The MetaChip concept is demonstrated by using sol-gel encapsulated P450s to activate the prodrug cyclophosphamide, which is the major constituent of the anticancer drug Cytoxan, as well as other compounds that are activated by P450 metabolism. The MetaChip provides a high-throughput microscale alternative to currently used
in vitro
methods for human metabolism and toxicology screening based on liver slices, cultured human hepatocytes, purified microsomal preparations, or isolated and purified P450s. This technology creates opportunities for rapid and inexpensive assessment of ADME/Tox (absorption, distribution, metabolism, excretion/toxicology) at very early phases of drug development, thereby enabling unsuitable candidates to be eliminated from consideration much earlier in the drug discovery process.
Age-specific incidence of inherited versus sporadic cancers: A test of the multistage theory of carcinogenesis
Authors: Frank Steven A.
Published: January 2005

Knudson [Knudson, A. G. (1971)
Proc. Natl. Acad. Sci. USA
68, 820–823] suggested that progression of retinoblastoma follows from two mutational events. Individuals who inherit one mutated gene copy should follow an age-onset pattern set by only a single rate-limiting step for transformation, whereas normal individuals should follow an age-onset pattern set by two rate-limiting events. Knudson's analysis of inherited and sporadic cases of retinoblastoma supported this prediction. However, retinoblastoma has a peculiar age-onset pattern concentrated in early life, because the retinal tissue completes most of its cell division by 5 years of age. Here, I compare age-specific incidences of inherited and sporadic forms of colon cancer, a much more typical form of human cancer. My simple mathematical analysis based on multistage theory explains the observed differences in age-onset patterns between inherited and sporadic cases. I also analyze recent retinoblastoma data and provide a mathematical analysis and interpretation. My analysis supports Knudson's two-hit theory but is much simpler and easier to understand than the original mathematical theory, which was based on a complicated model of cell division in the retina. My simpler theory for retinoblastoma makes clear the common basis for understanding multistage progression in tissues as different as the retina and colon.
Mutation of the androgen receptor causes oncogenic transformation of the prostate
Authors: Han Guangzhou , Buchanan Grant , Ittmann Michael , Harris Jonathan M. , Yu Xiaoqing , DeMayo Francesco J. , Tilley Wayne , Greenberg Norman M.
Published: January 2005

Recent evidence demonstrates that the androgen receptor (AR) continues to influence prostate cancer growth despite medical therapies that reduce circulating androgen ligands to castrate levels and/or block ligand binding. Whereas the mutation, amplification, overexpression of AR, or cross-talk between AR and other growth factor pathways may explain the failure of androgen ablation therapies in some cases, there is little evidence supporting a causal role between AR and prostate cancer. In this study, we functionally and directly address the role whereby AR contributes to spontaneous cancer progression by generating transgenic mice expressing (
i
) AR-WT to recapitulate increased AR levels and ligand sensitivity, (
ii
) AR-T857A to represent a promiscuous AR ligand response, and (
iii
) AR-E231G to model altered AR function. Whereas transgenes encoding either AR-WT or AR-T857A did not cause prostate cancer when expressed at equivalent levels, expression of AR-E231G, which carries a mutation in the most highly conserved signature motif of the NH
2
-terminal domain that also influences interactions with cellular coregulators, caused rapid development of prostatic intraepithelial neoplasia that progressed to invasive and metastatic disease in 100% of mice examined. Taken together, our data now demonstrate the oncogenic potential of steroid receptors and implicate altered AR function and receptor coregulator interaction as critical determinants of prostate cancer initiation, invasion, and metastasis.
Redefining implicit and explicit memory: The functional neuroanatomy of priming, remembering, and control of retrieval
Authors: Schott Björn H. , Henson Richard N. , Richardson-Klavehn Alan , Becker Christine , Thoma Volker , Heinze Hans-Jochen , Düzel Emrah
Published: January 2005

We used event-related functional MRI to study awareness of prior episodes during memory retrieval and its relationship to the intention to retrieve memories. Participants completed cues with words from a prior list (intentional test) or with the first words that came to mind (incidental test). During both tests, explicit memory was separated from priming in the absence of explicit memory. Priming was associated with hemodynamic decreases in left fusiform gyrus and bilateral frontal and occipital brain regions; explicit memory was associated with bilateral parietal and temporal and left frontal increases. Retrieval intention did not change these patterns but was associated with activity in right prefrontal cortex. Our results provide firm evidence that implicit and explicit memory have distinct functional neuroanatomies, and that strategic control of retrieval engages brain structures distinct from those involved in both implicit and explicit memory. They have critical implications for theories of memory and consciousness, which often equate consciousness with control.
Abelson-interactor-1 promotes WAVE2 membrane translocation and Abelson-mediated tyrosine phosphorylation required for WAVE2 activation
Authors: Leng Yan , Zhang Jinyi , Badour Karen , Arpaia Enrico , Freeman Spencer , Cheung Pam , Siu Michael , Siminovitch Katherine
Published: January 2005

WAVE2 is a member of the Wiskott–Aldrich syndrome protein family of cytoskeletal regulatory proteins shown to link Rac activation to actin remodeling via induction of Arp 2/3 activity. WAVE2 is thought to be regulated by its positioning in a macromolecular complex also containing the Abelson-(Abl) interactor-1 (Abi-1) adaptor, but the molecular basis and biologic relevance of WAVE2 inclusion in this complex are ill defined. Here we show that Abi-1 binding to WAVE2 is mediated by discrete motifs in the Abi-1 coiled-coil and WAVE2 WAVE-homology domains and increases markedly in conjunction with Abi-1-WAVE2 translocation and colocalization at the leading edge in B16F1 cells after fibronectin stimulation. Abi-1 also couples WAVE2 to Abl after cell stimulation, an interaction that triggers Abl membrane translocation with WAVE2, Abi-1, and activated Rac, as well as Abl-mediated tyrosine phosphorylation and WAVE2 activation. By contrast, mutation of tyrosine residue Y150, identified here as the major site of Abl-mediated WAVE2 tyrosine phosphorylation, as well as disruption of WAVE2-Abi-1 binding, impairs induction of WAVE2-driven actin polymerization and its membrane translocation in association with activated Rac. Similarly, WAVE2 tyrosine phosphorylation and induction of membrane actin rearrangement are abrogated in fibroblasts lacking the Abl family kinase. Together, these data reveal that Abi-1-mediated coupling of Abl to WAVE2 promotes Abl-evoked WAVE2 tyrosine phosphorylation required to link WAVE2 with activated Rac and with actin polymerization and remodeling at the cell periphery.
Reconstitution of uridine-deletion precleaved RNA editing with two recombinant enzymes
Authors: Kang Xuedong , Rogers Kestrel , Gao Guanghan , Falick Arnold M. , Zhou Sharleen , Simpson Larry
Published: January 2005

Uridine insertion/deletion RNA editing in trypanosomatid mitochondria is a posttranscriptional RNA modification phenomenon required for translation of mitochondrial mRNAs. This process involves guide RNA-mediated cleavage at a specific site, insertion or deletion of Us from the 3′ end of the 5′ mRNA fragment, and ligation of the two mRNA fragments. The
Leishmania major
RNA ligase-containing complex protein 2 expressed in insect cells has a 3′–5′ exoribonuclease activity and was therefore renamed RNA editing exonuclease 1 (REX1). Recombinant REX1 specifically trims 3′ overhanging Us and stops at a duplex region. Evidence is presented that REX1 is responsible for deletion of the 3′ overhanging Us from the bridged mRNA 5′ cleavage fragment and that RNA editing ligase 1 is responsible for the ligation of the two mRNA cleavage fragments in U-deletion editing. The evidence involves both
in vivo
down-regulation of REX1 expression in
Trypanosoma brucei
by RNA interference and the reconstitution of precleaved U-deletion
in vitro
editing with only two recombinant enzymes: recombinant REX1 and recombinant RNA editing ligase 1.
The “Dashpot” Mechanism of Stretch-dependent Gating in MscS
Authors: Akitake Bradley , Anishkin Andriy , Sukharev Sergei
Published: January 2005

The crystal structure of the small conductance mechanosensitive channel (MscS) has been an invaluable tool in the search for the gating mechanism, however many functional aspects of the channel remain unsettled. Here we characterized the gating of MscS in Escherichia coli spheroplasts in a triple mutant (mscL−, mscS−, mscK−) background. We used a pressure clamp apparatus along with software developed in-lab to generate dose–response curves directly from two-channel recordings of current and pressure. In contrast to previous publications, we found that MscS exhibits essentially voltage-independent activation by tension, but at the same time strong voltage-dependent inactivation under depolarizing conditions. The MscS activation curves obtained under saturating ramps of pressure, at different voltages, gave estimates for the energy, area, and gating charge for the closed-to-open transition as 24 kT, 18 nm2, and +0.8, respectively. The character of activation and inactivation was similar in both K+ and Na+ buffers. Perhaps the most salient and intriguing property of MscS gating was a strong dependence on the rate of pressure application. Patches subjected to various pressure ramps from 2.7 to 240 mmHg/s revealed a midpoint of activation almost independent of rate. However, the resultant channel activity was dramatically lower when pressure was applied slowly, especially at depolarizing pipette voltages. It appears that MscS prefers to respond in full to abrupt stimuli but manages to ignore those applied slowly, as if the gate were connected to the tension-transmitting element via a velocity-sensitive “dashpot.” With slower ramps, channels inactivate during the passage through a narrow region of pressures below the activation midpoint. This property of “dumping” a slowly applied force may be important in environmental situations where rehydration of cells occurs gradually and release of osmolytes is not desirable. MscS often enters the inactivated state through subconducting states favored by depolarizing voltage. The inactivation rate increases exponentially with depolarization. Based on these results we propose a kinetic scheme and gating mechanism to account for the observed phenomenology in the framework of available structural information.
Examples of non-formal closed (𝑘-1)-connected manifolds of dimensions ≥4𝑘-1
Authors: Dranishnikov Alex , Rudyak Yuli
Published: January 2005

We construct closed

(
k
−
1
)

(k-1)

-connected manifolds of dimensions

≥
4
k
−
1

\ge 4k-1

that possess non-trivial rational Massey triple products. We also construct examples of manifolds

M
M

such that all the cup-products of elements of

H
k

(
M
)

H^k(M)

vanish, while the group

H

3
k
−
1

(
M
;

Q

)

H^{3k-1}(M;\mathbb {Q})

is generated by Massey products: such examples are useful for the theory of systols.
Measures of concordance determined by 𝐷₄-invariant measures on (0,1)²
Authors: Edwards H. , Mikusiński P. , Taylor M.
Published: January 2005

A measure,

μ
\mu

, on

(
0
,
1

)
2

(0,1)^2

is said to be

D
4

D_4

-invariant if its value for any Borel set is invariant with respect to the symmetries of the unit square. A function,

κ
\kappa

, generated in a certain way by a measure,

μ
\mu

, on

(
0
,
1

)
2

(0,1)^2

is shown to be a measure of concordance if and only if the generating measure is positive, regular,

D
4

D_4

-invariant, and satisfies certain inequalities. The construction examined here includes Blomqvist’s beta as a special case.
Computing the Fredholm index of Toeplitz operators with continuous symbols
Authors: Feldman Nathan , McGuire Paul
Published: January 2005

We show how to compute the Fredholm index of a Toeplitz operator with a continuous symbol constructed from any subnormal operator with compact self-commutator. We also show that the essential spectral pictures of such Toeplitz operators can be prescribed arbitrarily.
Sampling sets and closed range composition operators on the Bloch space
Authors: Ghatage Pratibha , Zheng Dechao , Zorboska Nina
Published: January 2005

We give a necessary and sufficient condition for a composition operator

C

ϕ

C_{\phi }

on the Bloch space to have closed range. We show that when

ϕ
\phi

is univalent, it is sufficient to consider the action of

C

ϕ

C_{\phi }

on the set of Möbius transforms. In this case the closed range property is equivalent to a specific sampling set satisfying the reverse Carleson condition.
Existence of solutions for three-point boundary value problems for second order equations
Authors: Henderson Johnny , Karna Basant , Tisdell Christopher
Published: January 2005

Shooting methods are employed to obtain solutions of the three-point boundary value problem for the second order equation,

y
=
f
(
x
,
y
,

y
′

)
,

y =f(x,y,y’),

y
(

x
1

)
=

y
1

,
 
y
(

x

3

)
−
y
(

x
2

)
=

y
2

,

y(x_1)=y_1, \ y(x_{3}) - y(x_2)=y_2,

where

f
:
(
a
,
b
)
×

R

2

→

R

f: (a,b) \times \mathbb R^2 \to \mathbb R

is continuous,

a
>

x
1

>

x
2

>

x
3

>
b
,

a > x_1 > x_2 > x_3 > b,

and

y
1

,

y
2

∈

R

,

y_1,y_2 \in \mathbb R,

and conditions are imposed implying that solutions of such problems are unique, when they exist.
On a multidimensional form of F. Riesz’s “rising sun" lemma
Authors: Korenovskyy A. , Lerner A. , Stokolos A.
Published: January 2005

A multidimensional version of the Riesz rising sun lemma is proved by means of a generalized dyadic process.
On a conjecture of D. Styer regarding univalent geometric and annular starlike functions
Authors: Bshouty D. , Lyzzaik A.
Published: January 2005

The aim of this paper is two-fold. First, to give a direct proof for the already established result of Styer which states that a univalent geometrically starlike function

f
f

is a univalent annular starlike function if

f
f

is bounded. Second, to show that the boundedness condition of

f
f

is necessary, thus disproving a conjecture of Styer.
An extension of Biran’s Lagrangian barrier theorem
Authors: Lu Guang-Cun
Published: January 2005

We use the Gromov-Witten invariants and a nonsqueezing theorem by the author to affirm a conjecture by P. Biran on the Lagrangian barriers.
Positive scalar curvature and minimal hypersurfaces
Authors: Seshadri Harish
Published: January 2005

We show that the minimal hypersurface method of Schoen and Yau can be used for the “quantitative” study of positive scalar curvature. More precisely, we show that if a manifold admits a metric

g
g

with

s
g

≥
|
T
|

s_g \ge \vert T \vert

or

s
g

≥
|
W
|

s_g \ge \vert W \vert

, where

s
g

s_g

is the scalar curvature of

g
g

,

T
T

any 2-tensor on

M
M

and

W
W

the Weyl tensor of

g
g

, then any closed orientable stable minimal (totally geodesic in the second case) hypersurface also admits a metric with the corresponding positivity of scalar curvature. A corollary pertaining to the topology of such hypersurfaces is proved in a special situation.
Recombinant Coagulation Factor VIIa in Major Liver Resection
Authors: Lodge J Peter A. , Jonas Sven , Oussoultzoglou Elie , Malagó Massimo , Jayr Christian , Cherqui Daniel , Anthuber Matthias , Mirza Darius F. , Kuhlman Luce , Bechstein Wolf-Otto , Díaz Juan Carlos Meneu , Tartiere Jack , Eyraud Daniel , Fridberg Marianne , Erhardtsen Elisabeth , Mimoz Oliver
Published: January 2005

Background

Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy.

Methods

Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities.

Results

The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04).

Conclusions

Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.
Effect of Carbon Dioxide Pneumoperitoneum on Development of Atelectasis during Anesthesia, Examined by Spiral Computed Tomography
Authors: Andersson Lena E. , Bååth Margaretha , Thörne Anders , Aspelin Peter , Odeberg-Wernerman Suzanne
Published: January 2005

Background

Anesthesia per se results in atelectasis development in the dependent regions of the lungs. The effect of pneumoperitoneum on atelectasis formation is not known. The aim of the current study was to measure by spiral computed tomography the effect of carbon dioxide pneumoperitoneum for laparoscopic surgery on the development of atelectasis, overall lung volume, and regional tissue volumes of gas and tissue.

Methods

Seven patients (American Society of Anesthesiologists physical status I), scheduled to undergo laparoscopic cholecystectomy, were observed. After induction of anesthesia, the patients were mechanically ventilated and positioned supine on the computed tomography table. Tomography of the lungs (10 mm spiral) was performed before and 10 min after induction of carbon dioxide pneumoperitoneum at an intraabdominal pressure of 11-13 mmHg. The Student t test was used for statistical analysis. A P value less than 0.05 was considered significant.

Results

Induction of pneumoperitoneum increased the mean atelectasis volume in the dependent lung regions by 66% (range, 11-170%). The overall lung volume and gas as well as tissue volume significantly decreased. Relative to the total lung volume, lung tissue volume increased, while gas volume decreased significantly. Both upper and lower lobes reacted the same way. A cranial displacement of the diaphragm between 1 and 3 cm (mean, 1.9 cm) was registered.

Conclusion

Pneumoperitoneum at an intraabdominal pressure level of 11-13 mmHg increased the volume of atelectasis. Because lung tissue volume increased in the lung, there may have been an opening of previously closed vessels, which could explain previously seen increase in arterial oxygenation after induction of pneumoperitoneum.
Opposing Actions of Etomidate on Cortical Theta Oscillations Are Mediated by Different γ-Aminobutyric Acid Type A Receptor Subtypes
Authors: Drexler Berthold , Roether Claire L. , Jurd Rachel , Rudolph Uwe , Antkowiak Bernd
Published: January 2005

Background

Cortical networks generate diverse patterns of rhythmic activity. Theta oscillations (4-12 Hz) are commonly observed during spatial learning and working memory tasks. The authors ask how etomidate, acting predominantly via gamma-aminobutyric acid type A (GABAA) receptors containing beta2 or beta3 subunits, affects theta activity in vitro.

Methods

To characterize the effects of etomidate, the authors recorded action potential firing together with local field potentials in slice cultures prepared from the neocortex of the beta3(N265M) knock-in mutant and wild type mice. Actions of etomidate were studied at 0.2 microm, which is approximately 15% of the concentration causing immobility ( approximately 1.5 microm).

Results

In preparations derived from wild type and beta3(N265M) mutant mice, episodes of ongoing activity spontaneously occurred at a frequency of approximately 0.1 Hz and persisted for several seconds. Towards the end of these periods, synchronized oscillations in the theta band developed. These oscillations were significantly depressed in slices from beta3(N265M) mutant mice (P < 0.05). In this preparation etomidate acts almost exclusively via beta2 subunit containing GABAA receptors. In contrast, no depression was observed in slices from wild type mice, where etomidate potentiates both beta2- and beta3-containing GABAA receptors.

Conclusions

At concentrations assumed to cause sedation and amnesia, etomidate depresses theta oscillations via beta2-containing GABAA receptors but enhances these oscillations by acting on beta3 subunit containing receptors. This indicates that the overall effect of the anesthetic reflects a balance between enhancement and inhibition produced by different GABAA receptor subtypes.
Central Nervous System Concentrations of Cyclooxygenase-2 Inhibitors in Humans
Authors: Dembo Gregory , Park Sang B. , Kharasch Evan D.
Published: January 2005

Background

Cyclooxygenase-2 (COX-2)-selective inhibitors (coxibs) are under investigation for the potential therapy, attenuation, or prevention of neuroinflammatory and neurodegenerative disorders. Coxibs are also a significant advance in pain therapy and are traditionally considered to achieve analgesia via peripheral effects. However, in animals, central nervous system (CNS) COX-2 activity and prostanoid concentrations are increased by peripheral inflammation, central sensitization has been proposed to account for long-term pain-related phenomena, and coxibs achieve significant cerebrospinal fluid (CSF) concentrations and may cause analgesia via CNS action. Nevertheless, it remains unknown whether or which coxibs reach the CNS in humans. This investigation determined whether coxibs can reach the CNS in humans, based on CSF concentrations.

Methods

Ten healthy human volunteers simultaneously received a single oral dose of celecoxib (200 mg), rofecoxib (50 mg), and valdecoxib (40 mg). Blood and CSF were serially sampled for 10 h, and plasma total and unbound and CSF coxib concentrations were quantified by mass spectrometry.

Results

Total plasma concentrations and time to maximum plasma concentration were similar among the three coxibs. In contrast, unbound (free) plasma concentrations differed significantly. Maximum unbound plasma concentrations were 1.4 +/- 0.5, 42 +/- 17, and 6.0 +/- 2.9 ng/ml, respectively, for celecoxib, rofecoxib, and valdecoxib. COX-2 inhibitors rapidly penetrated the CNS. Maximum CSF concentrations were 2 +/- 2, 57 +/- 25, and 10 +/- 4 ng/ml, respectively, for celecoxib, rofecoxib, and valdecoxib. CSF concentrations exceeding the median inhibitory concentration for COX-2 were achieved by rofecoxib and valdecoxib but not celecoxib.

Conclusions

These results show that coxibs do reach the CNS in humans, with rapid penetration, and in concentrations apparently sufficient to inhibit COX-2 activity. There were significant differences among coxibs in CSF penetration. Unbound (free) plasma coxib concentration was the major determinant of CSF concentration. This supports the hypothesis that coxibs may act, in part, in the human CNS, provide important new information on the mechanism and treatment of pain and may guide coxib selection for therapeutic trials when CNS penetration is desirable.
Intrathecal Morphine Reduces Allodynia after Peripheral Nerve Injury in Rats via Activation of a Spinal A1 Adenosine Receptor
Authors: Zhang Yong , Conklin Dawn R. , Li Xinhui , Eisenach James C.
Published: January 2005

Background

The degree to which intrathecally administered morphine can alleviate hypersensitivity in animals after peripheral nerve injury is controversial, and the mechanisms by which morphine works in these circumstances are uncertain. In normal animals, morphine induces adenosine release, and in vitro data suggest that this link is disrupted after peripheral nerve injury. Therefore, using a controlled, blinded study design, the authors tested intrathecal morphine efficacy in rats with peripheral nerve injury and the role of spinal A1 adenosine receptors in the action of morphine.

Methods

Male rats underwent intrathecal catheter implantation and lumbar spinal nerve ligation, resulting in hypersensitivity to tactile stimulation of the paw. Intrathecal morphine alone or with naloxone or the specific A1 adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentyxanthine (DPCPX), was administered, and withdrawal threshold to von Frey filament application to the hind paw was determined.

Results

Intrathecal morphine (0.25-30 microg) dose-dependently reversed mechanical hypersensitivity after spinal nerve ligation, with an ED50 of 0.79 microg. The effect of morphine was blocked by intrathecal naloxone. Intrathecal DPCPX alone had no effect on withdrawal threshold after spinal nerve ligation but completely reversed the effect of morphine, with an ID50 of 5.6 microg.

Conclusions

This study is in accord with two recent reports that support short-term efficacy of intrathecal morphine to reverse hypersensitivity to mechanical stimuli in animal models of neuropathic pain. Despite previous studies demonstrating that morphine releases less adenosine after peripheral nerve injury, the current study suggests that the antihypersensitivity effect of morphine in these conditions is totally reliant on A1 adenosine receptor activation.
Studies on overwintering of bluetongue viruses in insects
Authors: White David M. , Wilson William C. , Blair Carol D. , Beaty Barry J.
Published: January 2005

Bluetongue viruses (BTVs) are economically important arboviruses that affect sheep and cattle. The overwintering mechanism of BTVs in temperate climates has eluded researchers for many years. Many arboviruses overwinter in their invertebrate vectors. To test the hypothesis that BTVs overwinter in their vertically infected insect vectors, Culicoides sonorensis larvae were collected from long-term study sites in northern Colorado, USA, and assayed for the presence of BTV RNA by nested RT-PCR. Sequences from BTV RNA segment 7 were detected in 30 % (17/56) of pools composed of larvae and pupae collected in 1998 and in 10 % (31/319) of pools composed of adults reared from larvae collected in 1996. BTV was not isolated from the insects. Additionally, Culicoides cell-culture lines derived from material collected at one of the sites, or derived from insect samples collected during a BTV outbreak, contained BTV RNA segment 7. In contrast, segment 2 RNA was detected at half the rate of segment 7 RNA in the field-collected larvae and was only detected in the Culicoides cell lines with one of two primer sets. These data suggest that BTVs could overwinter in the insect vector and that there is reduced expression of the outer capsid genes during persistent infection.
Neuroblastoma cell-adapted yellow fever virus: mutagenesis of the E protein locus involved in persistent infection and its effects on virus penetration and spread
Authors: Vlaycheva Leonssia , Nickells Michael , Droll Deborah A. , Chambers Thomas J.
Published: January 2005

Persistent infection of mouse neuroblastoma NB41A3 cells with yellow fever 17D virus generates viral variants which exhibit defective cell penetration, poor cell-to-cell spread, small plaque size and reduced growth efficiency, caused by substitution of glycine for aspartic acid or glutamic acid at positions 360 and 362 in the envelope protein. These positions occur within a charge cluster, Asp360-Asp361-Glu362, located in domain III, near its interface with domain I. To characterize further the molecular basis for the variant phenotype, a series of mutant viruses containing substitutions at position 360, 361 and 362, were studied for effects on the cell culture properties typical of the neuroblastoma-adapted variant. Most substitutions at position 360 gave rise to viruses that were very defective in cell penetration, growth efficiency and cell-to-cell spread, whereas substitution with glutamic acid yielded a virus indistinguishable from parental yellow fever 17D. Substitution with lysine was not tolerated and substitution with asparagine resulted in frequent wild-type revertants. A glycine residue was not tolerated at position 361, but substitution at 362 yielded a small plaque virus, similar to the effect of substitution at position 360. These data indicate that the yellow fever virus E protein contains a locus within domain III where a negative-charge cluster is important for optimal function of this domain in virus-cell interactions beyond the stage of virus attachment. Modelling predictions suggest that the mutations alter the local properties of the loop within domain III, and may compromise interactions of this domain with an adjacent region of domain I during conformational changes that occur in the E protein in association with virus entry.
Dendritic-cell infection by human cytomegalovirus is restricted to strains carrying functional UL131–128 genes and mediates efficient viral antigen presentation to CD8+ T cells
Authors: Gerna Giuseppe , Percivalle Elena , Lilleri Daniele , Lozza Laura , Fornara Chiara , Hahn Gabriele , Baldanti Fausto , Revello M. Grazia
Published: January 2005

Human cytomegalovirus (HCMV) genetic determinants of endothelial-cell tropism and virus transfer to leukocytes (both polymorphonuclear and monocyte) have been recently identified in the UL131–128 genes. Here it is documented that the same genetic determinants of HCMV are responsible for monocyte-derived dendritic-cell (DC) tropism, i.e. all endotheliotropic and leukotropic strains of HCMV are also DC-tropic (or dendrotropic). In fact, all recent clinical HCMV isolates and deletion mutants sparing the UL131–128 locus as well as the endotheliotropic revertants AD169 and Towne were able to productively infect DC following co-culture with infected endothelial cells. On the contrary, the same clinical isolates extensively propagated in human fibroblasts, the UL131–128 deletion mutants and the reference laboratory strains were not. Peak extracellular virus titres in DC were reached 4–7 days post-infection (p.i.). Viral proteins pp65 and p72 were detected 1–3 h p.i., involving the great majority of DC 24 h p.i., while gB was abundantly detected 96 h p.i., when a cytopathic effect first appeared. Infection of DC with cell-free virus released into the medium could only be achieved with HCMV strains extensively adapted to growth in endothelial cells, reaching the peak titres 10 days p.i. DC infected for 24 h with cell-free virus and incubated for 16 h with autologous peripheral blood mononuclear cells were found to act as a potent stimulator of both HCMV-specific CD4+- and CD8+-mediated immune responses, as determined by cytokine flow cytometry. DC incubated with inactivated crude whole viral antigen preparations were only capable of eliciting a significant CD4+-mediated immune response.
Enteroviruses 76, 89, 90 and 91 represent a novel group within the species Human enterovirus A
Authors: Oberste M. Steven , Maher Kaija , Michele Suzanne M. , Belliot Gaël , Uddin Moyez , Pallansch Mark A.
Published: January 2005

Molecular methods have enabled the rapid identification of new enterovirus (EV) serotypes that would have been untypable using existing neutralizing antisera. Nineteen strains of four new EV types termed EV76 (11 isolates), EV89 (two isolates), EV90 (four isolates) and EV91 (two isolates), isolated from clinical specimens from patients in France (one isolate) and Bangladesh (18 isolates), are described. Nucleotide sequences encoding the VP1 capsid protein (882–888 nt) are less than 65 % identical to the homologous sequences of the recognized human EV serotypes, but within each group the sequences are more than 78 % identical. The deduced amino acid sequences of the complete capsid (P1) region are more than 94 % identical within type but less than 76 % identical to those of the recognized serotypes. For both VP1 and P1, the 19 isolates are monophyletic by type with respect to all other EV serotypes. Using the proposed molecular typing scheme, these data support their identification as four new types within the species Human enterovirus A (HEV-A). In almost all cases, the VP1 sequences were more similar to those of some simian EVs than to the human EVs. Partial 3D sequences of all 19 isolates also clustered within HEV-A; they were monophyletic as a group, but not by type, suggesting that recombination has occurred among viruses of these four types. Partial 3D sequences were more closely related to those of simian EVs than to human viruses in HEV-A. These results suggest that the four new types may represent a new subgroup within HEV-A, in addition to the existing human and simian subgroups.