bluuebunny/crossref_metadata_2025 huggingface dataset:
Hitting time in regular sets and logarithm law for rapidly mixing dynamical systems
Authors: Galatolo Stefano
Published: April 2010

We prove that if a system has superpolynomial (faster than any power law) decay of correlations (with respect to Lipschitz observables), then the time

τ
(
x
,

S

r

)

\tau (x,S_{r})

is needed for a typical point

x
x

to enter for the first time a set

S

r

=
{
x
:
f
(
x
)
≤
r
}

S_{r}=\{x:f(x)\leq r\}

which is a sublevel of a Lipschitz function

f
f

scales as

1

μ
(

S

r

)

\frac {1}{\mu (S_{r})}

i.e.,
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="limit Underscript r right-arrow 0 Endscripts StartFraction log tau left-parenthesis x comma upper S Subscript r Baseline right-parenthesis Over minus log r EndFraction equals limit Underscript r right-arrow 0 Endscripts StartFraction log mu left-parenthesis upper S Subscript r Baseline right-parenthesis Over log r EndFraction period">

lim

r
→
0

log
⁡
τ
(
x
,

S

r

)

−
log
⁡
r

=

lim

r
→
0

log
⁡
μ
(

S

r

)

log
⁡
r

.

\begin{equation*} \underset {r\rightarrow 0}{\lim }\frac {\log \tau (x,S_{r})}{-\log r}=\underset {r\rightarrow 0}{\lim }\frac {\log \mu (S_{r})}{\log r}. \end{equation*}

This generalizes a previous result obtained for balls. We will also consider relations with the return time distributions, an application to observed systems and to the geodesic flow in negatively curved manifolds.
On the number of universal sofic groups
Authors: Thomas Simon
Published: April 2010

If

C
H

CH

fails, then there exist

2

2

ℵ

0

2^{2^{\aleph _{0}}}

universal sofic groups up to isomorphism.
On the codimension growth of 𝐺-graded algebras
Authors: Aljadeff Eli
Published: April 2010

Let

W
W

be an associative PI-affine algebra over a field

F
F

of characteristic zero. Suppose

W
W

is

G
G

-graded where

G
G

is a finite group. Let

exp
⁡
(
W
)

\exp (W)

and

exp
⁡
(

W

e

)

\exp (W_{e})

denote the codimension growth of

W
W

and of the identity component

W

e

W_{e}

, respectively. We prove

exp
⁡
(
W
)
≤

|

G

|

2

exp
⁡
(

W

e

)
.

\exp (W)\leq |G|^2 \exp (W_{e}).

This inequality had been conjectured by Bahturin and Zaicev.
The weak Lefschetz property and powers of linear forms in 𝕂[𝕩,𝕪,𝕫]
Authors: Schenck Hal , Seceleanu Alexandra
Published: April 2010

We show that an Artinian quotient of an ideal

I
⊆

K

[
x
,
y
,
z
]

I \subseteq \mathbb {K}[x,y,z]

generated by powers of linear forms has the Weak Lefschetz Property. If the syzygy bundle of

I
I

is semistable, the property follows from results of Brenner-Kaid. Our proof works without this hypothesis, which typically does not hold.
Baire category and the weak bang-bang property for continuous differential inclusions
Authors: De Blasi F. , Pianigiani G.
Published: April 2010

For continuous differential inclusions the classical bang-bang property is known to fail, yet a weak form of it is established here, in the case where the right hand side is a multifunction whose values are closed convex and bounded sets with nonempty interior contained in a reflexive and separable Banach space. Our approach is based on the Baire category method.
Generalizations of Gershgorin disks and polynomial zeros
Authors: Melman A.
Published: April 2010

We derive inclusion regions for the eigenvalues of a general complex matrix that are generalizations of Gershgorin disks, along with nonsingularity conditions. We then apply these results to the location of zeros of polynomials.
Uniform asymptotic expansions of the Tricomi-Carlitz polynomials
Authors: Lee K. , Wong R.
Published: April 2010

The Tricomi-Carlitz polynomials satisfy the second-order linear difference equation
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="left-parenthesis n plus 1 right-parenthesis f Subscript n plus 1 Superscript left-parenthesis alpha right-parenthesis Baseline left-parenthesis x right-parenthesis minus left-parenthesis n plus alpha right-parenthesis x f Subscript n Superscript left-parenthesis alpha right-parenthesis Baseline left-parenthesis x right-parenthesis plus f Subscript n minus 1 Superscript left-parenthesis alpha right-parenthesis Baseline left-parenthesis x right-parenthesis equals 0 comma n greater-than-or-equal-to 1 comma">

(
n
+
1
)

f

n
+
1

(
α
)

(
x
)
−
(
n
+
α
)

x

f
n

(
α
)

(
x
)
+

f

n
−
1

(
α
)

(
x
)
=
0
,

n
≥
1
,

\begin{equation*} (n+1)f_{n+1}^{(\alpha )}(x)-(n+\alpha )\,x\,f_n^{(\alpha )}(x)+ f_{n-1}^{(\alpha )}(x)=0, \qquad \qquad n\geq 1, \end{equation*}

with initial values

f
0

(
α
)

(
x
)
=
1

f_0^{(\alpha )}(x)=1

and

f
1

(
α
)

(
x
)
=
α
x

f_1^{(\alpha )}(x)=\alpha x

, where

x
x

is a real variable and

α
\alpha

is a positive parameter. An asymptotic expansion is derived for these polynomials by using the turning-point theory for three-term recurrence relations developed by Wang and Wong [Numer. Math. 91(2002) and 94(2003)]. The result holds uniformly in regions containing the critical values

x
=
±
2

/

ν

x=\pm 2/\sqrt {\nu }

, where

ν
=
n
+
2
α
−
1

/

2

\nu =n+2\alpha -1/2

.
Algebraic cycles of a fixed degree
Authors: Hu Wenchuan
Published: April 2010

In this paper, the homotopy groups of Chow variety

C

p
,
d

(

P

n

)

C_{p,d}(\mathbb {P}^n)

of effective

p
p

-cycles of degree

d
d

are proved to be stable in the sense that

p
p

or

n
n

increases. We also obtain a negative answer to a question by Lawson and Michelsohn on homotopy groups for the space of degree two cycles.
Uniqueness for a stochastic inviscid dyadic model
Authors: Barbato D. , Flandoli F. , Morandin F.
Published: April 2010

For the deterministic dyadic model of turbulence, there are examples of initial conditions in

l

2

l^{2}

which have more than one solution. The aim of this paper is to prove that uniqueness, for all

l

2

l^{2}

-initial conditions, is restored when a suitable multiplicative noise is introduced. The noise is formally energy preserving. Uniqueness is understood in the weak probabilistic sense.
On the existence of embeddings into modules of finite homological dimensions
Authors: Takahashi Ryo , Yassemi Siamak , Yoshino Yuji
Published: April 2010

Let

R
R

be a commutative Noetherian local ring. We show that

R
R

is Gorenstein if and only if every finitely generated

R
R

-module can be embedded in a finitely generated

R
R

-module of finite projective dimension. This extends a result of Auslander and Bridger to rings of higher Krull dimension, and it also improves a result due to Foxby where the ring is assumed to be Cohen-Macaulay.
Automorphism groups of small simple groups of finite Morley rank
Authors: Frécon Olivier
Published: April 2010

IfGGis a minimal connected simple group of finite Morley rank with a nontrivial Weyl group, then its connected definable automorphism groups are inner.
Tangencies between holomorphic maps and holomorphic laminations
Authors: Eremenko A. , Gabrielov A.
Published: April 2010

We prove that the set of leaves of a holomorphic lamination of codimension one that are tangent to a germ of a holomorphic map is discrete.
On the exact degree of ℚ(√𝕒₁,√𝕒₂,…,√𝕒_{ℓ}) over ℚ
Authors: Balasubramanian R. , Luca F. , Thangadurai R.
Published: April 2010

Let

S
=
{

a
1

,

a
2

,
…
,

a
ℓ

}

S =\{a_1, a_2, \ldots , a_\ell \}

be a finite set of non-zero integers. In this paper, we give an exact formula for the degree of the multi-quadratic field

Q

(

a
1

,

a
2

,
…
,

a
ℓ

)

\mathbb {Q}(\sqrt {a_1}, \sqrt {a_2},\ldots , \sqrt {a_\ell })

over

Q

\mathbb {Q}

. To do this, we compute the relative density of the set of prime numbers

p
p

for which all the

a
i

a_i

’s are simultaneously quadratic residues modulo

p
p

in two ways.
Approximation of probability distributions by convex mixtures of Gaussian measures
Authors: Bacharoglou Athanassia
Published: April 2010

Let
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="script upper A Subscript script plus Baseline equals left-brace a equals left-parenthesis a Subscript n Baseline right-parenthesis element-of intersection Underscript p greater-than 1 Endscripts script l Subscript p Baseline colon a Subscript n Baseline greater-than 0 comma for-all n element-of double-struck upper N right-brace">

A

+

=
{
a
=
(

a

n

)
∈

⋂

p
>
1

ℓ

p

:

a

n

>
0
,

∀
n
∈

N

}

\mathcal {A_{+}}=\{a=(a_{n})\in \bigcap _{p>1}\ell _{p}:a_{n}>0,\,\forall n\in \mathbb {N}\}

and let

{

ϕ

j

}

j
=
1

∞

\{\phi _{j}\}_{j=1}^{\infty }

be an enumeration of all normal distributions with mean a rational number and variance

1

n

2

,

n
=
1
,
2
…

\frac {1}{n^{2}},\,n=1,2\dots

. We prove that there exists an

a
∈

A

+

a\in \mathcal {A_{+}}

such that every probability density function, continuous, with compact support in

R

\mathbb {R}

, can be approximated in

L

1

L^{1}

and

L

∞

L^{\infty }

norm simultaneously by the averages

1

∑

j
=
1

n

a

j

∑

j
=
1

n

a

j

ϕ

j

\frac {1}{\sum _{j=1}^{n}a_{j}}\,\sum _{j=1}^{n}a_{j}\phi _{j}

. The set of such sequences is a dense

G

δ

G_{\delta }

set in

A

+

\mathcal {A_{+}}

and contains a dense positive cone.
Another proof for the removable singularities of the heat equation
Authors: Hui Kin Ming
Published: April 2010

We give two different simple proofs for the removable singularities of the heat equation in

(
Ω
∖
{

x
0

}
)
×
(
0
,
T
)

(\Omega \setminus \{x_0\})\times (0,T)

, where

x
0

∈
Ω
⊂

R

n

x_0\in \Omega \subset \mathbb {R}^n

is a bounded domain with

n
≥
3

n\ge 3

. We also give a necessary and sufficient condition for removable singularities of the heat equation in

(
Ω
∖
{

x
0

}
)
×
(
0
,
T
)

(\Omega \setminus \{x_0\})\times (0,T)

for the case

n
=
2

n=2

.
Best possible global bounds for Jensen functional
Authors: Simic Slavko
Published: April 2010

We determine the form of the best possible global bounds for the Jensen functional on the real line. Thereby, previous results on this topic are essentially improved. Some applications in Analysis and Information Theory are also given.
Higher order shuffle regularization for multiple zeta values
Authors: Li Zhong-hua
Published: April 2010

We study the higher order shuffle regularization for multiple zeta values and define higher order regularized shuffle relations. We find that higher order regularized shuffle relations can be deduced from the group-like property of the Drinfel’d associator.
Keratin 8/18 Modulation of Protein Kinase C-mediated Integrin-dependent Adhesion and Migration of Liver Epithelial Cells
Authors: Bordeleau François , Galarneau Luc , Gilbert Stéphane , Loranger Anne , Marceau Normand
Published: April 2010

Keratins are intermediate filament (IF) proteins of epithelial cells, expressed as pairs in a lineage/differentiation manner. Hepatocyte and hepatoma cell IFs are made solely of keratins 8/18 (K8/K18), the hallmark of all simple epithelia. Cell attachment/spreading (adhesion) and migration involve the formation of focal adhesions at sites of integrin interactions with extracellular matrix, actin adaptors such as talin and vinculin, and signaling molecules such as focal adhesion kinase (FAK) and member(s) of the protein kinase C (PKC) family. Here, we identify the novel PKCδ as mediator of the K8/K18 modulation of hepatoma cell adhesion and migration. We also demonstrate a K8/K18-dependent relationship between PKCδ and FAK activation through an integrin/FAK-positive feedback loop, in correlation with a reduced FAK time residency at focal adhesions. Notably, a K8/K18 loss results to a time course modulation of the receptor of activated C-kinase-1, β1-integrin, plectin, PKC, and c-Src complex formation. Although the K8/K18 modulation of hepatocyte adhesion also occurs through a PKC mediation, these differentiated epithelial cells exhibit minimal migrating ability, in link with marked differences in protein partner content and distribution. Together, these results uncover a key regulatory function for K8/K18 IFs in the PKC-mediated integrin/FAK-dependent adhesion and migration of simple epithelial cells.
Activation of the Mitogen-activated Protein Kinase, Slt2p, at Bud Tips Blocks a Late Stage of Endoplasmic Reticulum Inheritance in Saccharomyces cerevisiae
Authors: Li Xia , Du Yunrui , Siegel Steven , Ferro-Novick Susan , Novick Peter
Published: April 2010

Inheritance of the endoplasmic reticulum (ER) requires Ptc1p, a type 2C protein phosphatase of Saccharomyces cerevisiae . Genetic analysis indicates that Ptc1p is needed to inactivate the cell wall integrity (CWI) MAP kinase, Slt2p. Here we show that under normal growth conditions, Ptc1p inactivates Slt2p just as ER tubules begin to spread from the bud tip along the cortex. In ptc1Δ cells, the propagation of cortical ER from the bud tip to the periphery of the bud is delayed by hyperactivation of Slt2p. The pool of Slt2p that controls ER inheritance requires the CWI pathway scaffold, Spa2p, for its retention at the bud tip, and a mutation within Slt2p that prevents its association with the bud tip blocks its role in ER inheritance. These results imply that Slt2p inhibits a late step in ER inheritance by phosphorylating a target at the tip of daughter cells. The PI4P5-kinase, Mss4p, is an upstream activator of this pool of Slt2p. Ptc1p-dependant inactivation of Slt2p is also needed for mitochondrial inheritance; however, in this case, the relevant pool of Slt2p is not at the bud tip.
RNF-121 Is an Endoplasmic Reticulum-Membrane E3 Ubiquitin Ligase Involved in the Regulation of β-Integrin
Authors: Darom Amir , Bening-Abu-Shach Ulrike , Broday Limor
Published: April 2010

We report on the characterization of RNF-121, an evolutionarily conserved E3 ligase RING finger protein that is expressed in the endoplasmic reticulum (ER) of various cells and tissues in Caenorhabditis elegans . Inactivation of RNF-121 induced an elevation in BiP expression and increased the sensitivity of worms to ER stress. Genetic analysis placed RNF-121 downstream of the unfolded protein response (UPR) regulator protein kinase-like endoplasmic reticulum kinase (PERK). We identify PAT-3::GFP, the β subunit of the heterodimeric integrin receptors, as an RNF-121 substrate; whereas induction of RNF-121 expression reduced the level of PAT-3::GFP in the gonad distal tip cells, inhibition of RNF-121 led to the accumulation of stably bound PAT-3::GFP inclusions. Correspondingly, overexpression of RNF-121 during early stages of gonad development led to aberrations in germline development and gonad migration that overlap with those observed after PAT-3 inactivation. The formation of these gonad abnormalities required functional ER-associated degradation (ERAD) machinery. Our findings identify RNF-121 as an ER-anchored ubiquitin ligase that plays a specific role in the ERAD pathway by linking it to the regulation of the cell adhesion integrin receptors.
Arf3 Is Activated Uniquely at thetrans-Golgi Network by Brefeldin A-inhibited Guanine Nucleotide Exchange Factors
Authors: Manolea Florin , Chun Justin , Chen David W. , Clarke Ian , Summerfeldt Nathan , Dacks Joel B. , Melançon Paul
Published: April 2010

It is widely assumed that class I and II Arfs function interchangeably throughout the Golgi complex. However, we report here that in vivo, Arf3 displays several unexpected properties. Unlike other Golgi-localized Arfs, Arf3 associates selectively with membranes of the trans-Golgi network (TGN) in a manner that is both temperature-sensitive and uniquely dependent on guanine nucleotide exchange factors of the BIGs family. For example, BIGs knockdown redistributed Arf3 but not Arf1 from Golgi membranes. Furthermore, shifting temperature to 20°C, a temperature known to block cargo in the TGN, selectively redistributed Arf3 from Golgi membranes. Arf3 redistribution occurred slowly, suggesting it resulted from a change in membrane composition. Arf3 knockdown and overexpression experiments suggest that redistribution is not responsible for the 20°C block. To investigate in more detail the mechanism for Arf3 recruitment and temperature-dependent release, we characterized several mutant forms of Arf3. This analysis demonstrated that those properties are readily separated and depend on pairs of residues present at opposite ends of the protein. Furthermore, phylogenetic analysis established that all four critical residues were absolutely conserved and unique to Arf3. These results suggest that Arf3 plays a unique function at the TGN that likely involves recruitment by a specific receptor.
Studying the co-evolution of protein families with the Mirrortree web server
Authors: Ochoa David , Pazos Florencio
Published: April 2010

Summary: The Mirrortree server allows to graphically and interactively study the co-evolution of two protein families, and investigate their possible interactions and functional relationships in a taxonomic context. The server includes the possibility of starting from single sequences and hence it can be used by non-expert users.

Availability and Implementation: The web server is freely available at http://csbg.cnb.csic.es/mtserver. It was tested in the main web browsers. Adobe Flash Player is required at the client side to perform the interactive assessment of co-evolution.

Contact:  pazos@cnb.csic.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
Antiamnesic Activity of an Ayurvedic Formulation Chyawanprash in Mice
Authors: Parle Milind , Bansal Nitin
Published: April 2010

Chyawanprash (Chy) is an ayurvedic formulation commonly consumed in Indian households. Chy is a comprehensive herbal tonic, prepared from around 50 herbs employing anwala (Emblica officinalis) as the basic ingredient. The present study was undertaken to explore the beneficial effects of Chy (at the dose of 1 and 2% w/w of diet) administered daily for 15 successive days in mice with memory deficits. A total of 228 mice divided in 38 groups were employed in this study. Morris water maze, Hebb‐Williams maze and elevated plus maze served as exteroceptive memory models, whereas scopolamine (Sco)‐induced amnesia and alprazolam (Alp)‐induced amnesia served as interoceptive memory models. The brain acetylcholinesterase activity, brain thiobarbituric acid reactive substances (TBARS) and reduced glutathione levels (GSH) were also estimated. The administration of Chy for 15 consecutive days significantly protected the animals from developing memory impairment. Furthermore, there was a significant decrease in brain TBARS and increase in GSH levels after administration of Chy (2% w/w), thereby indicating decreased free radical generation and increased scavenging of free radical, respectively. Thus, Chy may prove to be a useful remedy for the management of Alzheimer’s disease owing to its antioxidant effect, pro‐cholinergic action and/or antiamnesic potential.
Baseline characteristics and outcomes of patients with heart failure receiving bronchodilators in the CHARM programme
Authors: Hawkins Nathaniel M. , Wang Duolao , Petrie Mark C. , Pfeffer Marc A. , Swedberg Karl , Granger Christopher B. , Yusuf Salim , Solomon Scott D. , Östergren Jan , Michelson Eric L. , Pocock Stuart J. , Maggioni Aldo P. , McMurray John J.V. ,   for the CHARM Investigators and Committees
Published: April 2010

Aims

Heart failure (HF) and chronic obstructive pulmonary disease are common partners. Bronchodilators are associated with adverse cardiovascular outcomes in patients with pulmonary disease. The outcome of patients with HF prescribed bronchodilators is poorly defined.

Methods and results

The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme randomized 7599 patients with symptomatic HF to receive candesartan or placebo. The relative risk conveyed by bronchodilator therapy was examined using a multivariable Cox proportional hazards model. The prevalence of bronchodilator therapy was similar in patients with reduced and preserved systolic function (respectively, 8.7 vs. 9.2%, P = 0.46). Beta‐blocker utilization was markedly lower in patients receiving bronchodilators compared with those without (overall 31.9 vs. 57.6%, P < 0.0001). Bronchodilator use was associated with increased all‐cause mortality [HR 1.26 (1.09–1.45), P = 0.0015], cardiovascular death [HR 1.21 (1.03–1.42), P = 0.0216], HF hospitalization [HR 1.49 (1.29–1.72), P < 0.0001], and major adverse cardiovascular events [HR 1.32 (1.17–1.76), P < 0.0001]. The adverse outcomes were consistent in patients with reduced and preserved systolic function. No significant interaction was observed between bronchodilators and beta‐blockade with respect to outcomes.

Conclusion

Bronchodilator use is a powerful independent predictor of worsening HF and increased mortality in a broad spectrum of patients with HF. Whether this relates to a toxic effect of bronchodilators, underlying pulmonary disease, or both is unclear and warrants further investigation.
Social learning in a non-social reptile (
Geochelone carbonaria
)
Authors: Wilkinson Anna , Kuenstner Karin , Mueller Julia , Huber Ludwig
Published: April 2010

The ability to learn from the actions of another is adaptive, as it is a shortcut for acquiring new information. However, the evolutionary origins of this trait are still unclear. There is evidence that group-living mammals, birds, fishes and insects can learn through observation, but this has never been investigated in reptiles. Here, we show that the non-social red-footed tortoise (
Geochelone carbonaria
) can learn from the actions of a conspecific in a detour task; non-observer animals (without a conspecific demonstrator) failed. This result provides the first evidence that a non-social species can use social cues to solve a task that it cannot solve through individual learning, challenging the idea that social learning is an adaptation for social living.
Breaking the trade-off: rainforest bats maximize bandwidth and repetition rate of echolocation calls as they approach prey
Authors: Schmieder Daniela A. , Kingston Tigga , Hashim Rosli , Siemers Björn M.
Published: April 2010

Both mammals and birds experience a performance trade-off between producing vocalizations with high bandwidths and at high repetition rate. Echolocating bats drastically increase repetition rate from 2–20 calls s−1up to about 170 calls s−1prior to intercepting airborne prey in order to accurately track prey movement. In turn, bandwidth drops to about 10–30 kHz for the calls of this ‘final buzz’. We have now discovered that Southeast Asian rainforest bats (in the vespertilionid subfamilies Kerivoulinae and Murininae) are able to maintain high call bandwidths at very high repetition rates throughout approach to prey. Five species ofKerivoulaandPhoniscusproduced call bandwidths of between 78 and 170 kHz at repetition rates of 140–200 calls s−1and two ofMurinaat 80 calls s−1. The ‘typical’ and distinct drop in call frequency was present in none of the seven species. This stands in striking contrast to our present view of echolocation during approach to prey in insectivorous bats, which was established largely based on European and American members of the same bat family, the Vespertilionidae. Buzz calls ofKerivoula pellucidahad mean bandwidths of 170 kHz and attained maximum starting frequencies of 250 kHz which makes them the most broadband and most highly pitched tonal animal vocalization known to date. We suggest that the extreme vocal performance of the Kerivoulinae and Murininae evolved as an adaptation to echolocating and tracking arthropods in the dense rainforest understorey.
Intercellular mechanotransduction during multicellular morphodynamics
Authors: Kim Jin-Hong , Dooling Lawrence J. , Asthagiri Anand R.
Published: April 2010

Multicellular structures are held together by cell adhesions. Forces that act upon these adhesions play an integral role in dynamically re-shaping multicellular structures during development and disease. Here, we describe different modes by which mechanical forces are transduced in a multicellular context: (i) indirect mechanosensing through compliant substratum, (ii) cytoskeletal ‘tug-of-war’ between cell–matrix and cell–cell adhesions, (iii) cortical contractility contributing to line tension, (iv) stresses associated with cell proliferation, and (v) forces mediating collective migration. These modes of mechanotransduction are recurring motifs as they play a key role in shaping multicellular structures in a wide range of biological contexts. Tissue morphodynamics may ultimately be understood as different spatio-temporal combinations of a select few multicellular transformations, which in turn are driven by these mechanotransduction motifs that operate at the bicellular to multicellular length scale.
Biomechanical effects of environmental and engineered particles on human airway smooth muscle cells
Authors: Berntsen P. , Park C. Y. , Rothen-Rutishauser B. , Tsuda A. , Sager T. M. , Molina R. M. , Donaghey T. C. , Alencar A. M. , Kasahara D. I. , Ericsson T. , Millet E. J. , Swenson J. , Tschumperlin D. J. , Butler J. P. , Brain J. D. , Fredberg J. J. , Gehr P. , Zhou E. H.
Published: April 2010

The past decade has seen significant increases in combustion-generated ambient particles, which contain a nanosized fraction (less than 100 nm), and even greater increases have occurred in engineered nanoparticles (NPs) propelled by the booming nanotechnology industry. Although inhalation of these particulates has become a public health concern, human health effects and mechanisms of action for NPs are not well understood. Focusing on the human airway smooth muscle cell, here we show that the cellular mechanical function is altered by particulate exposure in a manner that is dependent upon particle material, size and dose. We used Alamar Blue assay to measure cell viability and optical magnetic twisting cytometry to measure cell stiffness and agonist-induced contractility. The eight particle species fell into four categories, based on their respective effect on cell viability and on mechanical function. Cell viability was impaired and cell contractility was decreased by (i) zinc oxide (40–100 nm and less than 44 μm) and copper(II) oxide (less than 50 nm); cell contractility was decreased by (ii) fluorescent polystyrene spheres (40 nm), increased by (iii) welding fumes and unchanged by (iv) diesel exhaust particles, titanium dioxide (25 nm) and copper(II) oxide (less than 5 μm), although in none of these cases was cell viability impaired. Treatment with hydrogen peroxide up to 500 μM did not alter viability or cell mechanics, suggesting that the particle effects are unlikely to be mediated by particle-generated reactive oxygen species. Our results highlight the susceptibility of cellular mechanical function to particulate exposures and suggest that direct exposure of the airway smooth muscle cells to particulates may initiate or aggravate respiratory diseases.
Nonlinear stability of the one-domain approach to modelling convection in superposed fluid and porous layers
Authors: Hill Antony A. , Carr Magda
Published: April 2010

Studies of the nonlinear stability of fluid/porous systems have been developed very recently. A two-domain modelling approach has been adopted in previous works, but was restricted to specific configurations. The extension to the more general case of a Navier–Stokes modelled fluid over a porous material was not achieved for the two-domain approach owing to the difficulties associated with handling the interfacial boundary conditions. This paper addresses this issue by adopting a one-domain approach, where the governing equations for both regions are combined into a unique set of equations that are valid for the entire domain. It is shown that the nonlinear stability bound, in the one-domain approach, is very sharp and hence excludes the possibility of subcritical instabilities. Moreover, the one-domain approach is compared with an equivalent two-domain approach, and excellent agreement is found between the two.
Pictish symbols revealed as a written language through application of Shannon entropy
Authors: Lee Rob , Jonathan Philip , Ziman Pauline
Published: April 2010

Many prehistoric societies have left a wealth of inscribed symbols for which the meanings are lost. For example, the Picts, a Scottish, Iron Age culture, left a few hundred stones expertly carved with highly stylized petroglyph symbols. Although the symbol scripts are assumed to convey information, owing to the short (one to three symbols), small (less than 1000 symbols) and often fragmented nature of many symbol sets, it has been impossible to conclude whether they represent forms of written language. This paper reports on a two-parameter decision-tree technique that distinguishes between the different character sets of human communication systems when sample sizes are small, thus enabling the type of communication expressed by these small symbol corpuses to be determined. Using the technique on the Pictish symbols established that it is unlikely that they are random or sematographic (heraldic) characters, but that they exhibit the characteristics of written languages.
Asymptotic study of imperfect interfaces in conduction through a granular composite material
Authors: Andrianov Igor V. , Bolshakov Vladimir I. , Danishevs’kyy Vladyslav V. , Weichert Dieter
Published: April 2010

Imperfect bonding between the constitutive components can greatly affect the properties of composite structures. We propose an asymptotic analysis of different types of imperfect interfaces arising in the problem of conduction through a simple cubic array of spherical inclusions. The performed study is based on the two-scale asymptotic homogenization method. The microscopic problem on the unit cell is solved using the underlying principles of the boundary-shape perturbation technique. The influence of the interface properties on the effective conductivity and on the local potential and flux fields is studied.
Constitutive modelling of arteries
Authors: Holzapfel Gerhard A. , Ogden Ray W.
Published: April 2010

This review article is concerned with the mathematical modelling of the mechanical properties of the soft biological tissues that constitute the walls of arteries. Many important aspects of the mechanical behaviour of arterial tissue can be treated on the basis of elasticity theory, and the focus of the article is therefore on the constitutive modelling of the anisotropic and highly nonlinear elastic properties of the artery wall. The discussion focuses primarily on developments over the last decade based on the theory of deformation invariants, in particular invariants that in part capture structural aspects of the tissue, specifically the orientation of collagen fibres, the dispersion in the orientation, and the associated anisotropy of the material properties. The main features of the relevant theory are summarized briefly and particular forms of the elastic strain-energy function are discussed and then applied to an artery considered as a thick-walled circular cylindrical tube in order to illustrate its extension–inflation behaviour. The wide range of applications of the constitutive modelling framework to artery walls in both health and disease and to the other fibrous soft tissues is discussed in detail. Since the main modelling effort in the literature has been on the passive response of arteries, this is also the concern of the major part of this article. A section is nevertheless devoted to reviewing the limited literature within the continuum mechanics framework on the active response of artery walls, i.e. the mechanical behaviour associated with the activation of smooth muscle, a very important but also very challenging topic that requires substantial further development. A final section provides a brief summary of the current state of arterial wall mechanical modelling and points to key areas that need further modelling effort in order to improve understanding of the biomechanics and mechanobiology of arteries and other soft tissues, from the molecular, to the cellular, tissue and organ levels.
Under a neighbour's influence: public information affects stress hormones and behaviour of a songbird
Authors: Cornelius Jamie M. , Breuner Creagh W. , Hahn Thomas P.
Published: April 2010

Socially acquired information improves the accuracy and efficiency of environmental assessments and can increase fitness. Public information may be especially useful during unpredictable food conditions, or for species that depend on resources made less predictable by human disturbance. However, the physiological mechanisms by which direct foraging assessments and public information are integrated to affect behaviour remain largely unknown. We tested for potential effects of public information on the behavioural and hormonal response to food reduction by manipulating the social environment of captive red crossbills (
Loxia curvirostra
). Red crossbills are irruptive migrants that are considered sensitive to changes in food availability and use public information in decision making. Here, we show that public information can attenuate or intensify the release of glucocorticoids (i.e. stress hormones) during food shortage in red crossbills. The observed modulation of corticosterone may therefore be a physiological mechanism linking public information, direct environmental assessments and behavioural change. This mechanism would not only allow for public information to affect individual behaviour, but might also facilitate group decision making by bringing group members into more similar physiological states. The results further suggest that stressors affecting entire populations may be magnified in individual physiology through social interactions.
Plant green-island phenotype induced by leaf-miners is mediated by bacterial symbionts
Authors: Kaiser Wilfried , Huguet Elisabeth , Casas Jérôme , Commin Céline , Giron David
Published: April 2010

The life cycles of many organisms are constrained by the seasonality of resources. This is particularly true for leaf-mining herbivorous insects that use deciduous leaves to fuel growth and reproduction even beyond leaf fall. Our results suggest that an intimate association with bacterial endosymbionts might be their way of coping with nutritional constraints to ensure successful development in an otherwise senescent environment. We show that the phytophagous leaf-mining mothPhyllonorycter blancardella(Lepidoptera) relies on bacterial endosymbionts, most likelyWolbachia, to manipulate the physiology of its host plant resulting in the ‘green-island’ phenotype—photosynthetically active green patches in otherwise senescent leaves—and to increase its fitness. Curing leaf-miners of their symbiotic partner resulted in the absence of green-island formation on leaves, increased compensatory larval feeding and higher insect mortality. Our results suggest that bacteria impact green-island induction through manipulation of cytokinin levels. This is the first time, to our knowledge, that insect bacterial endosymbionts have been associated with plant physiology.
Recovery of mechano-electrical transduction in rat cochlear hair bundles after postnatal destruction of the stereociliar cross-links
Authors: Ebert J. , Fink S. , Koitschev A. , Walther P. , Langer M. G. , Lehmann-Horn F.
Published: April 2010

Mechano-electrical transduction (MET) in the stereocilia of outer hair cells (OHCs) was studied in newborn Wistar rats using scanning electron microscopy to investigate the stereociliar cross-links, Nomarski laser differential interferometry to investigate stereociliar stiffness and by testing the functionality of the MET channels by recording the entry of fluorescent dye, FM1-43, into stereocilia. Preparations were taken from rats on their day of birth (P0) or 1–4 days later (P1–P4). Hair bundles developed from the base to the apex and from the inner to outer OHC rows. MET channel responses were detected in apical coil OHCs on P1. To study the possible recovery of MET after disrupting the cross-links, the same investigations were performed after the application of Ca
2+
chelator 1,2-bis(o-aminophenoxy)ethane-
N
,
N
,
N
′,
N
′-tetraacetic acid (BAPTA) and allowing the treated samples to recover in culture medium for 0–20 h. We found that the structure and function were abolished by BAPTA. In P0–P1 samples, structural recovery was complete and the open probability of MET channels reached control values. In P3–P4 samples, complete recovery only occurred in OHCs of the outermost row. Although our results demonstrate an enormous recovery potential of OHCs in the postnatal period, the structural component restricts the potential for therapy in patients.
The function of the aerenchyma in arborescent lycopsids: evidence of an unfamiliar metabolic strategy
Authors: Green W. A.
Published: April 2010

Most species of the modern family Isoëtaceae (Quillworts) some other modern hydrophytes, use a metabolic pathway for carbon fixation that involves uptake of sedimentary carbon and enrichment of CO2in internal gas spaces as a carbon-concentrating mechanism. This metabolism, which is related to ‘aquatic CAM’, is characterized by morphological, physiological and biochemical adaptations for decreasing photorespirative loss, aerating roots and maintaining high growth rates in anoxic, oligotrophic, stressed environments. Some of the closest relatives of the Isoëtaceae were the ‘arborescent lycopsids’, which were among the dominant taxa in the coal swamps found in lowland ecosystems during the Carboniferous and Permian periods (approx. 300 Ma). Morphological, ecological and geochemical evidence supports the hypothesis that the arborescent lycopsids had an unusual metabolism similar to that of modern Isoëtaceae and processed a biogeochemically significant proportion of organically fixed carbon over a period of about 100 million years in the late Palaeozoic. The temporal coincidence between the dominance of plants with this metabolism and an anomalous global atmosphere (high O2; low CO2) supports the idea that biosphere feedbacks are important in regulating global climatic homeostasis. The potential influence of this metabolism on the global carbon cycle and its specific adaptive function suggest that it should perhaps be considered a fourth major photosynthetic pathway.
Temporal genetic change in the last remaining population of woolly mammoth
Authors: Nyström Veronica , Dalén Love , Vartanyan Sergey , Lidén Kerstin , Ryman Nils , Angerbjörn Anders
Published: April 2010

During the Late Pleistocene, the woolly mammoth (
Mammuthus primigenius
) experienced a series of local extinctions generally attributed to human predation or environmental change. Some small and isolated populations did however survive far into the Holocene. Here, we investigated the genetic consequences of the isolation of the last remaining mammoth population on Wrangel Island. We analysed 741 bp of the mitochondrial DNA and found a loss of genetic variation in relation to the isolation event, probably caused by a demographic bottleneck or a founder event. However, in spite of
ca
5000 years of isolation, we did not detect any further loss of genetic variation. Together with the relatively high number of mitochondrial haplotypes on Wrangel Island near the final disappearance, this suggests a sudden extinction of a rather stable population.
How does the Royal Family of Tudor rule the PIWI-interacting RNA pathway?
Authors: Siomi Mikiko C. , Mannen Taro , Siomi Haruhiko
Published: April 2010

PIWI (P-element-induced wimpy testis) proteins are a subset of the Argonaute proteins and are expressed predominantly in the germlines of a variety of organisms, including Drosophila and mammals. PIWI proteins associate specifically with PIWI-interacting RNAs (piRNAs), small RNAs that are also expressed predominantly in germlines, and silence transposable DNA elements and other genes showing complementarities to the sequences of associated piRNAs. This mechanism helps to maintain the integrity of the genome and the development of gametes. PIWI proteins have been shown recently to contain symmetrical dimethyl arginines (sDMAs), and this modification is mediated by the methyltransferase PRMT5 (also known as Dart5 or Capsuleen). It was then demonstrated that multiple members of the Tudor (Tud) family of proteins, which are necessary for gametogenesis in both flies and mice, associate with PIWI proteins specifically through sDMAs in various but particular combinations. Although Tud domains in Tud family members are known to be sDMA-binding modules, involvement of the Tudor family at the molecular level in the piRNA pathway has only recently come into focus.
Epigenetic propagation of CD4 expression is established by theCd4proximal enhancer in helper T cells
Authors: Chong Mark M.W. , Simpson Natalie , Ciofani Maria , Chen Grace , Collins Amélie , Littman Dan R.
Published: April 2010

The stability of a lineage program (cellular memory) is dependent on mechanisms that epigenetically maintain active or repressed states of gene expression (transcriptional memory). Although epigenetic silencing of genes has been clearly demonstrated from yeast to mammals, heritable maintenance of active transcription has been less clearly defined. To investigate the potential role of active transcriptional memory during lineage diversification, we employed targeted mutation of a positive-actingciselement in theCd4locus to determine the impact on CD4 expression and the differentiation of CD4+helper T cells in mice. We show that the proximal enhancer (E4P) ofCd4is essential for CD4 expression in immature CD4+8+thymocytes. Futhermore, its loss resulted in reduced and unstable expression of CD4 in mature T cells. However, if the enhancer was deleted after cells had already committed to the helper T-cell lineage, CD4 expression remained high and was stable upon cell division. “Active” histone modifications, once initiated byE4P, were also propagated independently of the enhancer. Thus,E4Pis responsible for establishing an epigenetically inherited activeCd4locus in the helper T-cell lineage. To our knowledge, this is the first genetic demonstration of active transcriptional memory in mammalian cells.
The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins
Authors: Humke Eric W. , Dorn Karolin V. , Milenkovic Ljiljana , Scott Matthew P. , Rohatgi Rajat
Published: April 2010

The transcriptional program orchestrated by Hedgehog signaling depends on the Gli family of transcription factors. Gli proteins can be converted to either transcriptional activators or truncated transcriptional repressors. We show that the interaction between Gli3 and Suppressor of Fused (Sufu) regulates the formation of either repressor or activator forms of Gli3. In the absence of signaling, Sufu restrains Gli3 in the cytoplasm, promoting its processing into a repressor. Initiation of signaling triggers the dissociation of Sufu from Gli3. This event prevents formation of the repressor and instead allows Gli3 to enter the nucleus, where it is converted into a labile, differentially phosphorylated transcriptional activator. This key dissociation event depends on Kif3a, a kinesin motor required for the function of primary cilia. We propose that the Sufu–Gli3 interaction is a major control point in the Hedgehog pathway, a pathway that plays important roles in both development and cancer.
Understanding neuronal connectivity through the post-transcriptional toolkit
Authors: Loya Carlos M. , Van Vactor David , Fulga Tudor A.
Published: April 2010

Post-transcriptional regulatory mechanisms have emerged as a critical component underlying the diversification and spatiotemporal control of the proteome during the establishment of precise neuronal connectivity. These mechanisms have been shown to be important for virtually all stages of assembling a neural network, from neurite guidance, branching, and growth to synapse morphogenesis and function. From the moment a gene is transcribed, it undergoes a series of post-transcriptional regulatory modifications in the nucleus and cytoplasm until its final deployment as a functional protein. Initially, a message is subjected to extensive structural regulation through alternative splicing, which is capable of greatly expanding the protein repertoire by generating, in some cases, thousands of functionally distinct isoforms from a single gene locus. Then, RNA packaging into neuronal transport granules and recognition by RNA-binding proteins and/or microRNAs is capable of restricting protein synthesis to selective locations and under specific input conditions. This ability of the post-transcriptional apparatus to expand the informational content of a cell and control the deployment of proteins in both spatial and temporal dimensions is a feature well adapted for the extreme morphological properties of neural cells. In this review, we describe recent advances in understanding how post-transcriptional regulatory mechanisms refine the proteomic complexity required for the assembly of intricate and specific neural networks.
CARM1 mediates the ligand-independent and tamoxifen-resistant activation of the estrogen receptor α by cAMP
Authors: Carascossa Sophie , Dudek Peter , Cenni Bruno , Briand Pierre-André , Picard Didier
Published: April 2010

The estrogen receptor α (ERα) is activated as a transcription factor by both estrogen and a large variety of other extracellular signals. The mechanisms of this ligand-independent activation, notably by cAMP signaling, are still largely unknown. We now close the gap in the signaling pathway between cAMP and ERα. Whereas the direct phosphorylation of ERα by the cAMP-activated protein kinase A (PKA) is dispensable, the phosphorylation of the coactivator-associated arginine methyltransferase 1 (CARM1) by PKA at a single serine is necessary and sufficient for direct binding to the unliganded hormone-binding domain (HBD) of ERα, and the interaction is necessary for cAMP activation of ERα. Sustained PKA activity promoting a constitutive interaction may contribute to tamoxifen resistance of breast tumors. Binding and activation involve a novel regulatory groove of the ERα HBD. As a result, depending on the activating signal, ERα recruits different coactivator complexes to regulate alternate sets of target genes.
Dicentric breakage at telomere fusions
Authors: Pobiega Sabrina , Marcand Stéphane
Published: April 2010

Nonhomologous end-joining (NHEJ) inhibition at telomeres ensures that native chromosome ends do not fuse together. But the occurrence and consequences of rare telomere fusions are not well understood. It is notably unclear whether a telomere fusion could be processed to restore telomere ends. Here we address the behavior of individual dicentrics formed by telomere fusion in the yeast Saccharomyces cerevisiae. Our approach was to first stabilize and amplify fusions between two chromosomes by temporarily inactivating one centromere. Next we analyzed dicentric breakage following centromere reactivation. Unexpectedly, dicentrics often break at the telomere fusions during progression through mitosis, a process that restores the parental chromosomes. This unforeseen result suggests a rescue pathway able to process telomere fusions and to back up NHEJ inhibition at telomeres.