bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel repair action of vitamin C upon in vivo oxidative DNA damage
Authors: Cooke Marcus S , Evans Mark D , Podmore Ian D , Herbert Karl E , Mistry Nalini , Mistry Pratibha , Hickenbotham Peter T , Hussieni Amina , Griffiths Helen R , Lunec Joseph
Published: July 2002

There appears to be a paucity of data examining the effect of dietary antioxidants on levels of oxidative DNA damage in vivo, limiting evidence‐based assessment of antioxidant efficacy, mechanisms and recommendation for optimal intake. We have examined levels of 8‐oxo‐2′‐deoxyguanosine (8‐oxodG) in mononuclear cell DNA, serum and urine from subjects undergoing supplementation with 500 mg/day vitamin C. Significant decreases in DNA levels of 8‐oxodG were seen, correlating strongly with increases in plasma vitamin C concentration. Furthermore we established a timecourse for sequential, significant increases in serum and urinary 8‐oxodG levels. These results illustrate, for the first time in humans, the kinetics of 8‐oxodG removal and processing in vivo, suggesting a role for vitamin C in the regulation of DNA repair enzymes and thereby demonstrating a non‐scavenging antioxidant effect.
Cloning of the peroxiredoxin gene family in rats and characterization of the fourth member
Authors: Matsumoto Akio , Okado Ayako , Fujii Tsuneko , Fujii Junichi , Egashira Masayuki , Niikawa Norio , Taniguchi Naoyuki
Published: July 2002

Peroxiredoxin (PRx) exhibits thioredoxin‐dependent peroxidase activity and constitutes a family of proteins. Four members of genes from rat tissues were isolated by PCR using degenerated primers based on the sequences which encode a pair of highly conserved Cys‐containing domains, and were then cloned to full‐length cDNAs. These included two genes which have previously been isolated in rats, PRx I and PRx II, and two rat homologues of PRx III and PRx IV. We showed, for the first time, the simultaneous expression of all four genes in various rat tissues by Northern blotting. Since a discrepancy exists regarding cellular distribution, we further characterized PRx IV by expressing it in COS‐1 cells. This clearly demonstrates that PRx IV is a secretory form and functions within the extracellular space.
Effects of reciprocal chimeras between the C‐terminal portion of third intracellular loops of the human dopamine D2 and D3 receptors
Authors: Filteau Frédéric , Veilleux François , Lévesque Daniel
Published: July 2002

The dopamine D3 receptor is a member of the G protein‐coupled superfamily of receptors. However, its coupling with intracellular events is still not well understood. We have performed chimera constructions in which amino acid residues located in a region of the receptor involved in the coupling with second messengers (the C‐terminal portion of the third intracellular loop) have been exchanged between dopamine D2 and D3 receptors. Chimera constructions did not modify substantially the pharmacological profiles, nor G protein coupling, as compared to their respective wild‐type receptors. However, the D2 receptor chimera, containing the C‐terminal portion of the third intracellular loop of the D3 receptor, has a lower potency to inhibit cyclic AMP production. The reciprocal construction generated a D3 receptor that is fully coupled to this second messenger pathway whereas, the native D3 receptor is uncoupled to this pathway in our transfected cells. These results suggest that the sequence selected is important for specific coupling characteristics shown by these two dopamine receptor homologues.
Thioredoxin peroxidase in the Cyanobacterium Synechocystis sp. PCC 6803
Authors: Yamamoto Hiroshi , Miyake Chikahiro , Dietz Karl-Josef , Tomizawa Ken-Ichi , Murata Norio , Yokota Akiho
Published: July 2002

The amino acid sequence deduced from the open reading frame designated sll0755 in Synechocystis sp. PCC 6803 is similar to the amino acid sequences of thioredoxin peroxidases from other organisms. In the present study, we found that a recombinant SLL0755 protein that was expressed in Escherichia coli was able to reduce H2O2 and tertiary butyl hydroperoxide with thioredoxin from E. coli as the electron donor. Targeted disruption of open reading frame sll0755 in Synechocystis sp. PCC 6803 cells completely eliminated the H2O2‐dependent and tertiary butyl hydroperoxide‐dependent photosynthetic evolution of oxygen and the electron flow in photosystem II. These results indicate that the product of open reading frame sll0755 is a thioredoxin peroxidase whose activities are coupled to the photosynthetic electron transport system in Synechocystis sp. PCC 6803.
A variational approach to chaotic dynamics in periodically forced nonlinear oscillators
Authors: Bosetto Elena , Serra Enrico
Published: July 2002

We prove that a class of problems containing the classical periodically forced pendulum equation displays the main features of chaotic dynamics. The approach is based on the construction of multibump type heteroclinic solutions to periodic orbits by the use of global variational methods.

On prouve qu’une classe de problèmes contenant l’équation du pendule forcé périodiquement possède les principales caractéristiques de la dynamique chaotique. Les techniques sont basées sur la construction d’orbites hétéroclines de type multibump asymptotiques à des solutions périodiques. Les methodes sont variationnelles globales.
Nonhomogeneous Cahn–Hilliard fluids
Authors: Boyer Franck
Published: July 2002

In this paper we are interested in the study of a model of nonhomogeneous diphasic incompressible flow. More precisely we consider a coupling of a Cahn–Hilliard and an incompressible Navier–Stokes equations where the densities of the phases are different.

For this general model we can only show the local existence of a unique very regular solution and the existence of weaker solutions is still an open problem. But, if we look at the behavior of the system when the densities tends to be equal (slightly nonhomogeneous case), we show the existence of a global weak solution and of a unique local strong solution (which is in fact global in 2D). Finally, an asymptotic stability result for the metastable states is shown in this slightly nonhomogeneous case.

Dans cet article, nous nous intéressons à l’étude d’un modèle d’écoulement diphasique nonhomogène incompressible. Plus précisément, nous considérons un couplage entre une équation de Cahn–Hilliard et une équation de Navier–Stokes incompressible dans lesquelles les densités des deux phases sont différentes.

Pour ce modèle général, nous pouvons seulement prouver l’existence locale et l’unicité d’une solution très régulière, l’existence de solutions plus faibles restant un problème ouvert. En revanche, si nous considérons le comportement du système quand les densités des deux phases sont proches (cas faiblement nonhomogène), nous montrons l’existence de solutions faibles globales et l’existence et l’unicité de solutions fortes locales (en fait globales en dimension 2). Enfin, un résultat de stabilité asymptotique des états métastables est établi, toujours dans le cas faiblement nonhomogène.
Sinai–Ruelle–Bowen measures for contracting Lorenz maps and flows
Authors: Metzger Roger J
Published: July 2002

We consider a large class of one-dimensional maps arising from the contracting Lorenz attractors for three dimensional flows: the eigenvalues

λ_2<λ_1<0<λ_3

of the flow at the singularity satisfy

λ_1+λ_3<0

(instead of

λ_1+λ_3>0

as in the classical geometric Lorenz models). Such flows were studied by A. Rovella who showed that non-uniform expansiveness is a persistent form of behavior (positive Lebesgue measure sets of parameters). Using mainly expansiveness, we prove the existence of absolutely continuous measures invariant under these maps, and from this fact we are able to construct Sinai–Ruelle–Bowen measures for the original flows that generate them.

Nous considérons une classe importante de transformations uni-dimensionelles provenant d’attracteurs de Lorenz contractants des flots en dimension 3: les valeurs propres

λ_2<λ_1<0<λ_3

du flot au point singulier satisfont

λ_1+λ_3<0

(au lieu de

λ_1+λ_3>0

, comme dans les modèles geòmétriques de Lorenz standards). Ces flots ont été etudiés par A. Rovella qui a montré que l’expansion non-uniforme a un comportament persistant (ensembles de paramètres de mesure positive). En utilisant cette expansion non-uniform, nous démonstrons l’existence de mesures invariantes par ces transformations qui sont absolutement continues. De ce fait, nous déduisons l’existence de mesures SRB pour le flots qui les induisent.
Existence of guided cylindrical TM-modes in a homogeneous self-focusing dielectric
Authors: Stuart Charles A. , Zhou Huan-Song
Published: July 2002

We establish the existence of nontrivial solutions for the nonlinear eigenvalue problem which describes self-trapped transverse magnetic field modes in a cylindrical optical fiber made from a self-focusing dielectric material. It amounts to finding solutions in the Sobolev space

H_0^1(0,∞)

of a singular second order differential equation which is quasilinear and, in an appropriate sense, asymptotically linear. Solutions are critical points of an energy functional which has a mountain pass structure, although for all relevant parameter values the problem is in resonance at infinity. The quasilinearity complicates the proof of a Palais–Smale condition, and the asymptotic linearity means that the standard methods for showing that a P-S sequence is bounded do not apply. Both the linearization and the asymptotic linearization have only continuous spectrum. The eigenvalues determine the wavelengths of self-trapped modes and our results establish the existence of such modes for the largest possible range of wavelengths.

On montre l’existence de solutions d’un problème aux valeurs propres non linéaire qui modélise des modes guidés cylindriques TM dans un fibre optique. Il s’agit de trouver des solutions dans l’espace de Sobolev

H_0^1(0,∞)

d’une équation différentielle singulière de deuxième ordre qui est quasilinéaire et asymptotiquement linéaire. Les solutions sont des points critiques d’une fonctionnelle ayant la structure du théorème du col mais qui se trouve dans un cas de résonance pour toutes les valeurs admises du paramètre. La forme quasilinéaire complique la vérification de la condition du Palais–Smale et le comportement à l’infini fait que les méthodes usuelles pour montrer que les suites P-S sont bornées ne s’appliquent pas. La linéarisation ainsi que la linéarisation à l’infini n’ont que du spectre continu. Les valeurs propres du problème non linéaire déterminent les longueurs d’onde des modes guidés et nos résultats établissent l’existence de tels modes pour la gamme maximum de longueurs d’ondes.
Critical nonlinearity exponent and self-similar asymptotics for Lévy conservation laws
Authors: Woyczyński Wojbor A , Biler Piotr , Karch Grzegorz
Published: July 2002

Nonlocal conservation laws of the form

u_t+\mathcal Lu+\nabla \cdot f(u)=0,

where

−\mathcal L

is the generator of a Lévy semigroup on

L^1(ℝ^n)

, are encountered in continuum mechanics as model equations with anomalous diffusion. They are generalizations of the classical Burgers equation. We study the critical case when the diffusion and nonlinear terms are balanced, e.g.

\mathcal L∼(−Δ)^{α/2}

,

1<α<2

,

f(s)∼s|s|^{r−1}

,

r=1+(α−1)/n

. The results include decay rates of solutions and their genuinely nonlinear asymptotic behavior as time

t

tends to infinity, determined by self-similar source solutions.
The structure and limiting behavior of locally optimal minimizers
Authors: Marcus Moshe , Zaslavski Alexander J.
Published: July 2002

We study the structure of locally optimal (

c

-optimal) minimizers of a class of second order variational problems on

R_+

. The problems are related to a model in thermodynamics introduced in [4]. We show that if

v

is a

c

-optimal nonperiodic minimizer, then the corresponding curve in the phase plane does not intersect itself. Using this fact we study the asymptotic behavior at infinity of

c

-optimal minimizers, and the structure of their limiting sets.

Nous étudions la structure des minimiseurs localement optimaux (

c

-optimaux) d'une classe de problèmes variationelles du second ordre sur

R_+

. Ces problèmes sont liés à un modèle de thermodinamique introduit dans [4]. Nous montrons que si

v

est um minimiseur non-périodique

c

-optimal, alors la courbe correspondante dans l'espace des phases ne s'auto-intersecte pas. En utilisant ce fait, nous étudions le comportement asymptotique à l'infini des minimiseurs

c

-optimaux, et la structure de leurs ensembles limites.
Nested axi-symmetric vortex rings
Authors: Buffoni B.
Published: July 2002

In an inviscid and incompressible fluid, we prove the existence of nested co-axial vortex rings moving at the same speed.

Pour un fluide idéal, nous montrons l’existence de tourbillons annulaires concentriques se déplaçant à la même vitesse.
Liouville theorems and blow up behaviour in semilinear reaction diffusion systems
Authors: Andreucci D. , Herrero M.A. , Velázquez J.J.L.
Published: July 2002

This paper is concerned with positive solutions of the semilinear system:

\tag{S}
\left\{\begin{matrix} u_{t} = \Delta u + \upsilon ^{p}, & p \geq 1, \\ \upsilon _{t} = \Delta \upsilon + u^{q}, & q \geq 1, \\ \end{matrix}\right.

which blow up at

x = 0

and

t = T < ∞

. We shall obtain here conditions on

p

,

q

and the space dimension

N

which yield the following bounds on the blow up rates:

\tag{1}
\begin{matrix} u\left(x,t\right) \leq C\left(T - t\right)^{ - \frac{p + 1}{pq - 1}}, & \upsilon \left(x,t\right) \leq C\left(T - t\right)^{ - \frac{q + 1}{pq - 1}}, \\ \end{matrix}

for some constant

C > 0

. We then use (1) to derive a complete classification of blow up patterns. This last result is achieved by means of a parabolic Liouville theorem which we retain to be of some independent interest. Finally, we prove the existence of solutions of (S) exhibiting a type of asymptotics near blow up which is qualitatively different from those that hold for the scalar case.
$C^∞$ regularity of solutions of the Levi equation
Authors: Citti G.
Published: July 2002

We will prove the

C^∞

regularity of the classical solutions of the equation

\mathcal{L}_{u} = q\frac{\left(1 + \left|\mathrm{grad}u\right|^{2}\right)^{3/ 2}}{1 + u_{t}^{2}}

where

\mathcal{L}u = u_{xx} + u_{yy} + 2\frac{u_{y} - u_{x}u_{t}}{1 + u_{t}^{2}}u_{xt} - 2\frac{u_{x} + u_{y}u_{t}}{1 + u_{t}^{2}}u_{yt} + \frac{u_{x}^{2} + u_{y}^{2}}{1 + u_{t}^{2}}u_{tt},

q \in C^{\infty }(\Omega )

and

q(ξ) ≠ 0

for every

ξ \in Ω

. This is a second order quasilinear equation, whose characteristic form has zero determinant at every point, and for every function

u

. However we will write it as a sum of squares of nonlinear vector fields, and we will extablish the result by means of a suitable freezing method.

Nous prouvons la régularité

C^∞

des solutions classiques de l’équation

\mathcal{L}u = q\frac{\left(1 + \left|gradu\right|^{2}\right)^{3/ 2}}{1 + u_{t}^{2}}

où

\mathcal{L}u = u_{xx} + u_{yy} + 2\frac{u_{y} - u_{x}u_{t}}{1 + u_{t}^{2}}u_{xt} - 2\frac{u_{x} + u_{y}u_{t}}{1 + u_{t}^{2}}u_{yt} + \frac{u_{x}^{2} + u_{y}^{2}}{1 + u_{t}^{2}}u_{tt},

q \in C^{\infty }\left(\Omega \right)

et

q(ξ) ≠ 0

pour tout

ξ \in Ω

. Il s’agit d’une équation quasilinéaire du second ordre, dont le déterminant du symbole principal est nul en tout point

ξ

, et pour toute fonction

u

. Nous écrivons l’équation comme une somme de carrés de champs de vecteurs, et nous prouvons le résultat en employant une méthode « freesing å.
Correction to “Properties of pseudoholomorphic curves in symplectisations I: Asymptotics”
Authors: Wysocki K. , Zehnder E. , Hofer H.
Published: July 2002

In our paper [1] we derived the proposition 2.1 from Lemma 2.2 which is clearly false and our aim is to give a proof of the proposition. We take the opportunity to remove also a flaw in the proof of Lemma 3.3. The results of [1] remain unaffected.
$ℤ_2$-equivariant Ljusternik–Schnirelman theory for non-even functionals
Authors: Ekeland I. , Ghoussoub N.
Published: July 2002

We develop an equivariant Ljusternik–Schnirelman theory for non-even functionals. We show that if one applies a

ℤ_2

-equivariant min-max procedure to a non-symmetric functional

\varphi

, then one gets either the usual critical points, defined by

\varphi'(x) = 0

or an interesting new class of points

x

, defined by

\varphi (x) = \varphi(−x)

and

\varphi'(x) = λ\varphi'(−x)

for some

λ > 0

. We call them “

ℤ_2

-resonant points”; by a “virtual critical point” we understand a point which is either critical or

ℤ_2

-resonant. We extend the classical existence and multiplicity results of Ljusternik–Schnirelman theory for critical points of even functionals to virtual critical points of non-even functionals. As an application we prove a bifurcation-type result for a class of non-homogenous semi-linear elliptic boundary value problems.

Nous construisons une théorie de Ljusternik–Schnirelman pour des fonctionnelles non symétriques. Plus précisément, nous montrons que si l’on applique une procédure de minimax

ℤ_2

-équivariante à une fonctionnelle non paire

\varphi

, l’on obtient d’une part les points critiques habituels, définis par

\varphi'(x) = 0

, et d’autre part des points d’un type nouveau, vérifiant,

\varphi(x) = \varphi(−x)

et

\varphi'(x) = λ\varphi,(−x)

pour certain

λ > 0

. Nous les baptisons «

ℤ_2

-résonants å, et nous appellerons « point critiques virtuels å les points qui sont, soit critiques au sens habituel, soit

ℤ_2

-résonants. Nous étendons alors la théorie classique de Ljusternik–Schnirelman pour les points critiques de fonctionnelles paires à la recherche des points critiques virtuels de fonctionnelles impaires. A titre d’application, nous obtenons un résultat de bifurcation pour une classe d’équations semi-linéaires elliptiques avec un second membre.
Complete blow up and global behaviour of solutions of ut − Δu = g(u)
Authors: Martel Yvan
Published: July 2002

For

u_0 \in L^∞(\Omega)

,

u_0 ≥ 0

, we study the global behaviour of solutions of the nonlinear heat equation (1). The domain

\Omega

is smooth and bounded and the nonlinearity

g

is nonnegative, nondecreasing and convex.

We show in particular that any nondecreasing solution blowing up at the finite time

T_{\mathrm{max}}

blows up completely in

\Omega

after

T_{\mathrm{max}}

. We apply this result to the description of all possible global behaviours of the solutions of (1) according to the value of

λ

. We show similar results when we introduce a notion of complete blow up in infinite time.

Pour

u_0 \in L^∞(\Omega)

,

u_0 ≥ 0

, on étudie le comportement global des solutions de l’équation de la chaleur non-linéaire

\tag{1}
\begin{cases}
u_{t} - \Delta u = \lambda g\left(u\right) & \text{dans }\left(0,T\right) \times \Omega , \\
u = 0 & \text{sur }\partial \Omega , \\
u\left(0\right) = u_{0} &\text{dans }\Omega .
\end{cases}

Le domaine

\Omega

est borné régulier, et la nonlinéarité

g

est positive, croissante et convexe.

On montre en particulier que toute solution croissante explosant au temps fini

T_{\mathrm{max}}

explose totalement dans

\Omega

après

T_{\mathrm{max}}

. On applique ce résultat à la description des comportements globaux possibles des solutions de (1) en fonction de

λ

. On montre des résultats similaires pour une notion d’explosion totale en temps infini que l’on introduit.
Multibump solutions for a class of Lagrangian systems slowly oscillating at infinity
Authors: Alessio Francesca , Montecchiari Piero
Published: July 2002

We prove the existence of infinitely many homoclinic solutions for a class of second order hamiltonian systems of the form

- \"u + u = \alpha (t)\nabla W(u)

where

W

is superquadratic and

\.{\alpha} (t)\rightarrow 0

,

0<\lim \inf \alpha(t)<\lim \sup \alpha(t)

as

t → + ∞

. In fact we prove that such a kind of systems admit a “multibump” dynamics.

On montre l’existence d’une infinité de solutions homoclines d’une classe de systèmes hamiltoniens du second ordre de la forme

- \"u + u = \alpha (t)\nabla W(u)

où

W

est superquadratique et

\.{\alpha} (t)\rightarrow 0

,

0<\lim \inf \alpha(t)<\lim \sup \alpha(t)

quand

t → + ∞

. On montre en particulier que cette famille des systèmes admet une dynamique “multi-bosses”.
A nonlinear oblique derivative boundary value problem for the heat equation Part 1: Basic results
Authors: Mehats Florian , Roquejoffre Jean-Michel
Published: July 2002

We study the heat equation

B_t − ΔB = 0

in the half-plane with the nonlinear oblique derivative condition

B_X = KBB_Z

on the boundary, where

(B_X, B_Z)

are respectively the normal and the tangential derivatives of

B

. The ultimate goal is to let

K → +∞

in the equations.

In this first part, we introduce self-similar solutions which verify an elliptic equation with the same nonlinear boundary condition. The main part of this first paper concerns this self-similar problem. It is well-posed and its solution is shown to be smooth, by means of boundary integral estimates. The originality of the approach is the robustness of the estimates with respect to

K

. The evolution problem itself admits global classical solutions which converge, as times tends to

+∞

, to the self-similar solution.

Nous étudions l’équation de la chaleur

B_t − ΔB = 0

dans le demi-plan, avec la condition aux limites

B_X = KBB_Z

sur la frontière. Il s’agit une condition oblique non linéaire,

B_X

et

B_Z

, étant respectivement les dérivées normale et tangentielle de
B
sur cet axe. Notre but final est de faire tendre

K

vers

+∞

dans les équations.

Ce travail est divisé en deux parties. Dans cette première partie, nous introduisons des solutions autosemblables associées à ce problème.

Ces solutions autosemblables vérifient un système elliptique, avec la même condition aux limites non linéaire sur l’axe, et l’étude de ce problème constitue la majeure partie de ce premier article. Nous prouvons, au moyen d’estimations intégrales à la frontière, qu’il est bien posé et que sa solution est régulière. L’apport de cette approche est la robustesse des estimations vis-à-vis de

K

. Le problème d’évolution proprement dit admet des solution classiques, qui convergent en temps vers la solution autosemblable.
Ergodic problem for the Hamilton–Jacobi–Bellman equation. II
Authors: Arisawa Mariko
Published: July 2002

We study the ergodic problem for the first-order Hamilton–Jacobi–Equations (HJBs), from the view point of controllabilities of underlying controlled deterministic systems. We shall give sufficient conditions for the ergodicity by the estimates of controllabilities.

Next, we shall give some results on the Abelian–Tauberian problem for the solutions of HJBs. Our solutions of HJBs satisfy the equations in the sense of viscosity solutions.

Nous étudions le problème ergodique pour les équations de Hamilton–Jacobi–Bellmans (HJBs). Nous utiliserons les notions des contrôlabilités dans les systèmes déterministes contrôlés pour donner des conditions suffisantes pour la convergenće ergodique.

Ensuite, nous donnons des résultats du problème de Abel et de Tauber pour les solutions des HJBs. Nos solutions des HJBs satisfont les équations au sens de la solution de la viscosité.
Minoration du temps d’existence pour l’équation de Klein–Gordon non-linéaire en dimension 1 d’espace
Authors: Delort J.-M.
Published: July 2002

Let

u

be a solution to the semilinear Klein–Gordon equation in one space dimension

\partial^2_tu-\partial^2_xu+u=F(u, \partial_tu,\partial_xu)

where

F

is a quadratic nonlinearity and the Cauchy data

u|_{t=0} = ϵu_0

,

∂_tu|_{t=0} = ϵu_1

are small in

C_0^∞

. Moriyama, Tonegawa and Tsutsumi have shown that the time of existence of the solution satisfies

\lim \inf_{ϵ→0}ϵ^2 \mathrm{log}\, T_ϵ > 0

. The aim of this paper is to prove that

\lim \inf_{ϵ→0}ϵ^2 \mathrm{log}\, T_ϵ ≥ A

for a constant

A

which can be explicitly computed from the Cauchy data and the nonlinearity.

Soit

u

la solution de l’équation de Klein–Gordon semi-linéaire en dimension 1 d’espace

\partial^2_tu-\partial^2_xu+u=F(u, \partial_tu,\partial_xu)

avec une nonlinéarité

F

quadratique et des données de Cauchy petites,

C^∞

à support compact,

u|_{t=0} = ϵu_0

,

∂_tu|_{t=0} = ϵu_1

. Moriyama, Tonegawa et Tsutsumi ont montré que le temps d’existence

T_ϵ

de la solution vérifie alors

\lim \inf_{ϵ→0}ϵ^2 \mathrm{log}\, T_ϵ > 0

. Le but de cet article est de montrer que

\lim \inf_{ϵ→0}ϵ^2 \mathrm{log}\, T_ϵ ≥ A

, où

A

est une constante explicite s’exprimant en fonction de

u_0

,

u_1

et de la nonlinéarité.
Enhanced GABA release in cell‐damaging conditions in the adult and developing mouse hippocampus
Authors: Saransaari Pirjo , Oja Simo S.
Published: July 2002

The release of [3H]GABA from hippocampul slices from adult (3‐month‐old) and developing (7‐day‐old) mice was studied in cell‐damaging conditions in vitro using a superfusion system. Cell damage was induced by modified superfusion media, including hypoxia, hypoglycemia, ischemia, the presence of free radicals and oxidative stress. The basal release of GABA from the immature and mature hippocampus was generally markedly increased in all cell‐damaging conditions. In 7‐day‐old mice the release was enhanced most in the presence of free radicals, 1.0 mM NaCN and ischemia, whereas in the adults 1.0 mM NaCN provoked the largest release of GABA, followed by ischemia and free radical‐containing media. Potassium stimulation (50mM K+) was still able to potentiate the release in all cell‐damaging conditions in both age groups. It was shown by superfusing the slices in Ca‐ and Na‐free media that ischemia‐induced GABA release was Ca‐independent, occurring by a reversed operation of Na‐dependent cell membrane carriers in both adult and developing hippocampus. Glutamate and its receptor agonists,N‐methyl‐d‐aspartate (NMDA), kainate and 2‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA), potentiated GABA release only in the immature hippocampus by a receptor‐mediated mechanism. The enhancement by kainate and AMPA receptors also operated under ischemic conditions. The massive amount of GABA released simultaneously with excitatory amino acids in the mature and immature hippocampus may be an important protective mechanism against excitotoxicity, counteracting harmful effects that lead to neuronal death. The GABA release induced by activation of presynaptic glutamate receptors may contribute particularly to the maintenance of homeostasis in the hippocampus upon impending hyper‐excitation.
IL‐1β and ICE mRNA are not altered upon β‐amyloid25–35 induced neurotoxicity in human neuroblastoma cells
Authors: Diana A. , Eriksson C. , Winblad B. , Schultzberg M.
Published: July 2002

The specific β‐amyloid25–35 fragment induced cellular degradation of the human neuroblastoma cell line SH‐SY5Y, but did not elicit an effect on the levels of interleukin‐1β and interleukin‐1β converting enzyme, as determined by semiquantitative reverse transcription‐polymerase chain reaction and immunocytochemical analysis. The assays revealed constitutive expression of these proteins both at mRNA and protein level.

It is conceivable that in the absence of glial elements, such as in the present neuroblastoma cell line, β‐amyloid triggers the toxicity through a direct action and/or through the production of other harmful molecules.
Dependence on zolpidem: a case report
Authors: Sakkas P. , Psarros C. , Masdrakis V. , Liappas J. , Christodoulou G.N.
Published: July 2002

We report the case of a patient with a history of zolpidem dependence. The patient, after a stressful life event, started using zolpidem. She rapidly developed tolerance and dependence, taking 50-100 mg, and sometimes up to 300 mg, of zolpidem daily. Also, our patient suffered episodes of altered consciousness, accompanied by visual hallucinations.
Effects of rifampin on the pharmacokinetics and pharmacodynamics of glyburide and glipizide
Authors: Niemi Mikko , Backman Janne T. , Neuvonen Mikko , Neuvonen Pertti J. , Kivistö Kari T.
Published: July 2002

Objective

To study the effects of rifampin (INN, rifampicin) on the pharmacokinetics and pharmacodynamics of glyburide (INN, glibenclamide) and glipizide, 2 sulfonylurea antidiabetic drugs.

Methods

Two separate, randomized, 2‐phase, crossover studies with an identical design were conducted. In each study, 10 healthy volunteers received 600 mg rifampin or placebo once daily for 5 days. On day 6, a single dose of 1.75 mg glyburide (study I) or 2.5 mg glipizide (study II) was administered orally. Plasma glyburide and glipizide and blood glucose concentrations were measured for 12 hours.

Results

In study I, rifampin decreased the area under the plasma concentration–time curve [AUC(0‐∞)] of glyburide by 39% (P < .001) and the peak plasma concentration by 22% (P = .01). The elimination half‐life of glyburide was shortened from 2.0 to 1.7 hours (P < .05) by rifampin. The blood glucose decremental AUC(0–7) (net area below baseline) and the maximum decrease in the blood glucose concentration were decreased by 44% (P = .05) and 36% (P < .001), respectively, by rifampin. In study II, rifampin decreased the AUC(0‐∞) of glipizide by 22% (P < .05) and shortened its half‐life from 3.0 to 1.9 hours (P = .01). No statistically significant differences in the blood glucose concentrations were found between the phases; however, 4 subjects had moderate hypoglycemia during the placebo phase but only 1 subject had moderate hypoglycemia during the rifampin phase.

Conclusions

Rifampin moderately decreased the plasma concentrations and effects of glyburide but had only a slight effect on glipizide. The mechanism underlying the interaction between rifampin and glyburide is probably induction of either CYP2C9 or P‐glycoprotein or both. Induction of CYP2C9 would explain the increased systemic elimination of glipizide. It is probable that the blood glucose–lowering effect of glyburide is reduced during concomitant treatment with rifampin. In some patients, the effects of glipizide may also be reduced by rifampin.

Clinical Pharmacology & Therapeutics (2001) 69, 400–406; doi: 10.1067/mcp.2001.115822
Comprehension, Utility, and Acceptability of a Multidomain Physical Functioning Report for Systemic Lupus Erythematosus Patients and Their Providers
Authors: Plantinga Laura C. , Xu Grace , Hoge Courtney , Vandenberg Ann , Dunlop‐Thomas Charmayne , Jones Brian D. , Johnson Jeremy , Drenkard Cristina , Lim S. Sam , Bowling C. Barrett
Published: July 2021

Objective

Patient‐provider discussions about functioning are often outside the scope of usual care for systemic lupus erythematosus (SLE), and tools to facilitate such discussions are lacking. The present study was undertaken to assess the comprehension, utility, and acceptability of a novel, individualized functioning report, the purpose of which is to facilitate patient–provider communication about functioning, in a predominantly Black SLE patient population.

Methods

Individualized reports (including sections with pictorial representations of participants' measured activities of daily living, falls, physical performance, perceived physical functioning, and community mobility from a previous pilot study visit) and surveys were emailed or mailed to 59 SLE patients. Ease of interpretation was dichotomized (“very easy” versus all other responses). Utility and acceptability were assessed by items relating to usefulness for care planning and comfort with discussing the report.

Results

Among 47 (79.7%) SLE patients who completed the survey (78.7% Black, 91.5% female, mean age 49.6 years), the reported ease of interpretation ranged from 70.2% to 85.1% across the report sections. Ease of interpretation was lower among those who were older, Black, and female and who had lower cognitive scores (P > 0.05 for all). Most reported that physical functioning domains of the report were useful for treatment or other care planning (70.2–80.5%) and that they felt comfortable discussing the report with a health care provider (93.2–100%).

Conclusion

We found that a novel functioning report for SLE patients was associated with high comprehension, utility, and acceptability. Future studies can help determine how an individualized functioning report could improve patient–provider communication in the clinic setting.
Predictive Value of Magnetic Resonance Imaging in Patients With Juvenile Idiopathic Arthritis in Clinical Remission
Authors: Mazzoni Marta , Pistorio Angela , Magnaguagno Francesca , Viola Stefania , Urru Alessia , Magnano Gian Michele , Ravelli Angelo , Malattia Clara
Published: July 2021

Objective

To define the prevalence of subclinical synovitis on magnetic resonance imaging (MRI) in a large cohort of patients with juvenile idiopathic arthritis (JIA) in clinical remission and to evaluate its predictive value in terms of disease flare and joint deterioration.

Methods

Ninety patients with clinically inactive JIA who underwent a contrast‐enhanced (CE)–MRI of a previously affected joint were retrospectively included. Each joint was evaluated for synovitis, tenosynovitis, and bone marrow edema. Baseline and follow‐up radiographs were assessed to evaluate structural damage progression.

Results

CE‐MRI was acquired in 45 wrists, 30 hips, 13 ankles, and 2 knees. Subclinical synovitis was detected in 59 (65.5%) of 90 patients and bone marrow edema in 42 (46.7%) of 90 patients. Fifty‐seven of 90 (63.3%) patients experienced a disease flare during follow‐up. Forty‐four of 59 (74.6%) patients with subclinical synovitis experienced a disease flare versus 13 (41.9%) of 31 patients with no residual synovitis on MRI (P = 0.002). The presence of subclinical synovitis was the best predictor of disease flare on multivariable regression analysis (hazard ratio [HR] 2.45, P = 0.003). Baseline and follow‐up radiographs were available for 54 patients, and 17 (31.5%) of 54 patients experienced radiographic damage progression. The presence of bone marrow edema (HR 4.40, P = 0.045) and being >17 years old (HR 3.51, P = 0.04) were strong predictors of joint damage progression in the multivariable analysis.

Conclusion

MRI‐detected subclinical inflammation was present in a large proportion of patients with JIA despite clinical remission. Subclinical synovitis and bone marrow edema have been shown to play a role in predicting the risk of disease relapse and joint deterioration, with potential implications for patients' management of the disease.
A Self‐Healable Polyelectrolyte Binder for Highly Stabilized Sulfur, Silicon, and Silicon Oxides Electrodes
Authors: Jin Biyu , Wang Dongyun , Zhu Juan , Guo Hongyu , Hou Yang , Gao Xiang , Lu Jianguo , Zhan Xiaoli , He Xiaojun , Zhang Qinghua
Published: July 2021

Large volume change, poor conductivity, and electrolyte soluble active materials intermediates have long been daunting challenges for sulfur, silicon, and silicon oxides electrode materials. A self‐healable polyelectrolyte binder is exploited by crosslinking polydopamine, phytic acid and poly(acrylamide‐co‐2‐(Dimethylamino)ethyl acrylate) in situ at room temperature through reconfigurable hydrogen bonds and ionic bonds. Therefore, the crosslinked binder network can readily recover its mechanical strength without extra stimulus, offering a reliable strategy for electrodes plagued by large volume change issue. Sulfur (S) and silicon (Si) electrodes prepared using the self‐healable polyelectrolyte binder can effectively maintain its structure integrity after long‐term cycling. In addition, the polar groups, especially negative‐charged phosphate ions empower the polyelectrolyte binder as a more effective binder than commercial poly(vinylidene fluoride) in terms of restraining lithium polysulfides shuttling and accelerating lithium ion transportation, as evidenced by in situ UV‐visible spectroscopy, density functional theory calculation and cyclic voltammetry. Consequently, high‐active materials loading S cathode, Si and SiO‐graphite anodes all achieve high area capacity and satisfying cycling stability by conveniently applying the advanced binder. This facile strategy for constructing multiuse binder illuminates versatile development in many energy storage systems.
A Stretchable and Transparent Electrode Based on PEGylated Silk Fibroin for In Vivo Dual‐Modal Neural‐Vascular Activity Probing
Authors: Cui Yajing , Zhang Fan , Chen Geng , Yao Lin , Zhang Nan , Liu Zhiyuan , Li Qingsong , Zhang Feilong , Cui Zequn , Zhang Keqin , Li Peng , Cheng Yuan , Zhang Shaomin , Chen Xiaodong
Published: July 2021

Transparent electrodes that form seamless contact and enable optical interrogation at the electrode–brain interface are potentially of high significance for neuroscience studies. Silk hydrogels can offer an ideal platform for transparent neural interfaces owing to their superior biocompatibility. However, conventional silk hydrogels are too weak and have difficulties integrating with highly conductive and stretchable electronics. Here, a transparent and stretchable hydrogel electrode based on poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and PEGylated silk protein is reported. PEGylated silk protein with poly(ethylene glycol) diglycidyl ether (PEGDE) improves the Young's modulus to 1.51–10.73 MPa and the stretchability to ≈400% from conventional silk hydrogels (<10 kPa). The PEGylated silk also helps form a robust interface with PEDOT:PSS thin film, making the hydrogel electrode synergistically incorporate superior stretchability (≈260%), stable electrical performance (≈4 months), and a low sheet resistance (≈160 ± 56 Ω sq−1). Finally, the electrode facilitates efficient electrical recording, and stimulation with unobstructed optical interrogation and rat‐brain imaging are demonstrated. The highly transparent and stretchable hydrogel electrode offers a practical tool for neuroscience and paves the way for a harmonized tissue–electrode interface.
Machine Learning to Predict Quasicrystals from Chemical Compositions
Authors: Liu Chang , Fujita Erina , Katsura Yukari , Inada Yuki , Ishikawa Asuka , Tamura Ryuji , Kimura Kaoru , Yoshida Ryo
Published: July 2021

Quasicrystals have emerged as the third class of solid‐state materials, distinguished from periodic crystals and amorphous solids, which have long‐range order without periodicity exhibiting rotational symmetries that are disallowed for periodic crystals in most cases. To date, more than one hundred stable quasicrystals have been reported, leading to the discovery of many new and exciting phenomena. However, the pace of the discovery of new quasicrystals has lowered in recent years, largely owing to the lack of clear guiding principles for the synthesis of new quasicrystals. Here, it is shown that the discovery of new quasicrystals can be accelerated with a simple machine‐learning workflow. With a list of the chemical compositions of known stable quasicrystals, approximant crystals, and ordinary crystals, a prediction model is trained to solve the three‐class classification task and its predictability compared to the observed phase diagrams of ternary aluminum systems is evaluated. The validation experiments strongly support the superior predictive power of machine learning, with the overall prediction accuracy of the phase prediction task reaching ≈0.728. Furthermore, analyzing the input–output relationships black‐boxed into the model, nontrivial empirical equations interpretable by humans that describe conditions necessary for stable quasicrystal formation are identified.
High Sensitive and Broadband Photodetectors Based on Hybrid PbI2 Nanosheet/CdSe Nanobelt
Authors: Li Chenyan , Li Weijun , Cheng Mingming , Yang Weiye , Tan Qiuhong , Wang Qianjin , Liu Yingkai
Published: July 2021

The limited detection of lead iodide (PbI2) to visible light hinders the further development of PbI2 in the field of optoelectronic applications. A photodetector based on PbI2 nanosheet/CdSe nanobelt (PbI2 NS/CdSe NB) is prepared for the first time. This composite structure exhibits broadband spectral photoresponse from ultraviolet (400 nm) to red (730 nm). More importantly, PbI2 NS/CdSe NB can promote the effective separation of electron–hole pairs and improve the photoelectric performance. Compared to single PbI2 NS, the PbI2 NS/CdSe NB photodetector exhibits higher light–dark current ratio (6.778 × 103 A), responsivity (347.57 A W−1), and detectivity (3.625 × 1015 Jones) under 490 nm illumination. A new strategy is provided here to design broadband and high‐performance photodetectors.
Biodegradable and Dual‐Responsive Polypeptide‐Shelled Cyclodextrin‐Containers for Intracellular Delivery of Membrane‐Impermeable Cargo
Authors: Kudruk Sergej , Pottanam Chali Sharafudheen , Linard Matos Anna Livia , Bourque Cole , Dunker Clara , Gatsogiannis Christos , Ravoo Bart Jan , Gerke Volker
Published: July 2021

The transport of membrane impermeable compounds into cells is a prerequisite for the efficient cellular delivery of hydrophilic and amphiphilic compounds and drugs. Transport into the cell's cytosolic compartment should ideally be controllable and it should involve biologically compatible and degradable vehicles. Addressing these challenges, nanocontainers based on cyclodextrin amphiphiles that are stabilized by a biodegradable peptide shell are developed and their potential to deliver fluorescently labeled cargo into human cells is analyzed. Host–guest mediated self‐assembly of a thiol‐containing short peptide or a cystamine‐cross‐linked polypeptide shell on cyclodextrin vesicles produce short peptide‐shelled (SPSVss) or polypeptide‐shelled vesicles (PPSVss), respectively, with redox‐responsive and biodegradable features. Whereas SPSVss are permeable and less stable, PPSVss effectively encapsulate cargo and show a strictly regulated release of membrane impermeable cargo triggered by either reducing conditions or peptidase treatment. Live cell experiments reveal that the novel PPSVSS are readily internalized by primary human endothelial cells (human umbilical vein endothelial cells) and cervical cancer cells and that the reductive microenvironment of the cells’ endosomes trigger release of the hydrophilic cargo into the cytosol. Thus, PPSVSS represent a highly efficient, biodegradable, and tunable system for overcoming the plasma membrane as a natural barrier for membrane‐impermeable cargo.
UV‐Sinterable Silver Oxalate‐Based Molecular Inks and Their Application for In‐Mold Electronics
Authors: Liu Xiangyang , Li Derek , Fukutani Hiroshi , Trudeau Paul , Khoun LoleÏ , Mozenson Olga , Sampson Kathleen L. , Gallerneault Mary , Paquet Chantal , Lacelle Thomas , Deore Bhavana , Ferrand Olivier , Ferrigno Julie , Malenfant Patrick R. L. , Kell Arnold J.
Published: July 2021

A new broadband UV light‐based processing method for a screen printable silver oxalate molecular ink is developed that enables structural electronics to be produced on complex thermoformed 3D objects. The production of these 3D devices is driven by the light‐induced reduction of silver oxalate to form an interfacial silver nanoparticle layer that allows the ink to transition to a viscous liquid intermediate and elongate up to 50% without cracking during thermoforming. Ultimately, this enables the development of 3D electronics devices with significantly less limitations on geometry, shape, size, and depth in comparison to commercially available inks. UV processing is also effective for 2D traces on low temperature PET substrate, where in situ produced silver nanoparticles can subsequently absorb light and further facilitate the rapid conversion of the silver oxalate to metallic silver through a self‐limiting thermal decomposition. The resulting traces have superior electrical properties and are produced in significantly less time in comparison to thermal sintering. Together, UV processing and the silver oxalate molecular ink serve as a platform for both the rapid production of conductive silver traces on low temperature substrates and the development of novel thermoformed 3D human‐machine interface devices, areas of interest for both academia and industry.
Genomic Insights into Myasthenia Gravis Identify Distinct Immunological Mechanisms in Early and Late Onset Disease
Authors: Handunnetthi Lahiru , Knezevic Bogdan , Kasela Silva , Burnham Katie L. , Milani Lili , Irani Sarosh R. , Fang Hai , Knight Julian C.
Published: July 2021

Objective

The purpose of this study was to identify disease relevant genes and explore underlying immunological mechanisms that contribute to early and late onset forms of myasthenia gravis.

Methods

We used a novel genomic methodology to integrate genomewide association study (GWAS) findings in myasthenia gravis with cell‐type specific information, such as gene expression patterns and promotor‐enhancer interactions, in order to identify disease‐relevant genes. Subsequently, we conducted additional genomic investigations, including an expression quantitative analysis of 313 healthy people to provide mechanistic insights.

Results

We identified several genes that were specifically linked to early onset myasthenia gravis including TNIP1, ORMDL3, GSDMB, and TRAF3. We showed that regulators of toll‐like receptor 4 signaling were enriched among these early onset disease genes (fold enrichment = 3.85, p = 6.4 × 10−3). In contrast, T‐cell regulators CD28 and CTLA4 were exclusively linked to late onset disease. We identified 2 causal genetic variants (rs231770 and rs231735; posterior probability = 0.98 and 0.91) near the CTLA4 gene. Subsequently, we demonstrated that these causal variants result in low expression of CTLA4 (rho = −0.66, p = 1.28 × 10−38 and rho = −0.52, p = 7.01 × 10−22, for rs231735 and rs231770, respectively).

Interpretation

The disease‐relevant genes identified in this study are a unique resource for many disciplines, including clinicians, scientists, and the pharmaceutical industry. The distinct immunological pathways linked to early and late onset myasthenia gravis carry important implications for drug repurposing opportunities and for future studies of drug development. ANN NEUROL 2021;90:455–463
Development and Mechanistic Studies of the Iridium‐Catalyzed C−H Alkenylation of Enamides with Vinyl Acetates: A Versatile Approach for Ketone Functionalization
Authors: Zhou Bo , Qi Xiaotian , Liu Peng , Dong Guangbin
Published: July 2021

Ketone functionalization is a cornerstone of organic synthesis. Herein, we describe the development of an intermolecular C−H alkenylation of enamides with the feedstock chemical vinyl acetate to access diverse functionalized ketones. Enamides derived from various cyclic and acyclic ketones reacted efficiently, and a number of sensitive functional groups were tolerated. In this iridium‐catalyzed transformation, two structurally and electronically similar alkenes—enamide and vinyl acetate—underwent selective cross‐coupling through C−H activation. No reaction partner was used in large excess. The reaction is also pH‐ and redox‐neutral with HOAc as the only stoichiometric by‐product. Detailed experimental and computational studies revealed a reaction mechanism involving 1,2‐Ir‐C migratory insertion followed by syn‐β‐acetoxy elimination, which is different from that of previous vinyl acetate mediated C−H activation reactions. Finally, the alkenylation product can serve as a versatile intermediate to deliver a variety of structurally modified ketones.