bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of enhancement of uterine involution and earlier initiation of post-partum cyclicity on the reproductive performance of buffalo
Authors: Ramoun A. A. , Darweish S. A. , Abou El-Ghait H. A. , Fattouh El-S. M.
Published: May 2006

The aim of the present work was to study the effect of either gonadotrophin-releasing hormone (GnRH)–prostaglandin PGF2α–GnRH (G–P–G) or equine chorionic gonadotrophin (eCG)–PGF2α–GnRH (eCG–P–G) regimes with or without intramuscular injection of ergometrine maleate (Methergin) within 24 h post partum on the uterine involution, initiation of post partum cyclicity and subsequent reproductive performance of buffalo. A total of 60 parturient Egyptian buffalos (2–4 lactations) were used to conduct this study. The involved animals were allotted into two main groups (A and B), each with 30 animals, on the basis of whether buffalo cows received an i.m. injection of 3 mg of Methergin within the first 24 h post partum (A, Meth. T) or not (B, Meth. NT). Each main group was subdivided into three subgroups: A1, A2 and A3 in case of A and B1, B2 and B3 in case of B. The G–P–G regime was applied on both A1 (Meth. T) and B1 (Meth. NT) buffalos, where each individual received two i.m. injections of 0.020 mg GnRH analogue (buserelin) at Days 18 and 33 post partum with i.m. injection of 25 mg PGF2α (Dinoprost) in between at Day 25. The eCG–P–G regime was applied on both A2 (Meth. T) and B2 (Meth. NT) buffalos, where each individual received i.m. injection of 1000 IU eCG, 25 mg of PGF2α (Dinoprost) and 0.020 mg of GnRH analogue (buserelin) at Days 8, 18 and 25 post partum, respectively. The A3 subgroup (Meth. T, alone) was control for A1 and A2 subgroups and the B3 subgroup was the non-treated control for all subgroups. There was a significant (P < 0.01) decrease in the days required for complete uterine involution in subgroups A1, B1 and A3, indicating the enhancement of uterine involution. The post partum cyclicity was initiated earlier in all of the treatment regimes applied in the present study, as was indicated by significant (P < 0.01) decrease in the days to first ovulation in these subgroups compared with the non-treated control subgroup. The reproductive performance of treated buffalos improved as was shown by the significant (P < 0.01) decrease in days to first service, days open and calving interval. It is concluded that enhancement of uterine involution and/or earlier initiation of post-partum cyclicity improve the reproductive performance of buffalos.
Bovine blastocyst diameter as a morphological tool to predict embryo cell counts, embryo sex, hatching ability and developmental characteristics after transfer to recipients
Authors: Hoelker Michael , Schmoll Friedrich , Schneider Hendrik , Rings Franca , Gilles Markus , Tesfaye Dawit , Jennen Danyel , Tholen Ernst , Griese Josef , Schellander Karl
Published: May 2006

The aim of the present study was to explore whether the blastocyst diameter and the zona thickness at 168 h after fertilisation are useful parameters to predict quality and viability of bovine in-vitro-produced (IVP)-embryos. Although significant (P < 0.05), the blastocyst diameter at 168 h correlated only poorly with the total number of cells (R2 = 0.13) and with the number of trophectoderm (TE) cells (R2 = 0.17). Hatched blastocysts (n = 66) at 216 h had a significantly greater mean diameter at 168 h (194.8 ± 16.8 µm) compared with either blastocysts that had started but not finished hatching at 216 h (n = 26, 178.4 ± 16.7 µm) or failed to commence hatching (n = 136, 162.7 ± 12.9 µm). Transfer of 101 IVP blastocysts to synchronised recipients resulted in the birth of 38 calves (38%). There were significantly more bull calves born than cow calves (P < 0.05), but this was not correlated with blastocyst diameter or zona thickness at 168 h. There was also no correlation between the diameter of blastocysts or the zona thickness at 168 h and parameters of subsequent developmental characteristics, including rates of pregnancy, resorptions and abortions, pregnancy duration, delivery to term and birthweight. Overall, the present results indicate that the blastocyst diameter and the zona thickness at 168 h are good predictors for subsequent hatching ability in vitro, but not for the number of TE cells, inner cell mass cells or total cells and neither for subsequent developmental characteristics after transfer to recipients.
Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer
Authors: Agrelo Ruben , Cheng Wen-Hsing , Setien Fernando , Ropero Santiago , Espada Jesus , Fraga Mario F. , Herranz Michel , Paz Maria F. , Sanchez-Cespedes Montserrat , Artiga Maria Jesus , Guerrero David , Castells Antoni , von Kobbe Cayetano , Bohr Vilhelm A. , Esteller Manel
Published: May 2006

Werner syndrome (WS) is an inherited disorder characterized by premature onset of aging, genomic instability, and increased cancer incidence. The disease is caused by loss of function mutations of the WRN gene, a RecQ family member with both helicase and exonuclease activities. However, despite its putative tumor-suppressor function, little is known about the contribution of WRN to human sporadic malignancies. Here, we report that WRN function is abrogated in human cancer cells by transcriptional silencing associated with CpG island-promoter hypermethylation. We also show that, at the biochemical and cellular levels, the epigenetic inactivation of WRN leads to the loss of WRN-associated exonuclease activity and increased chromosomal instability and apoptosis induced by topoisomerase inhibitors. The described phenotype is reversed by the use of a DNA-demethylating agent or by the reintroduction of WRN into cancer cells displaying methylation-dependent silencing of WRN. Furthermore, the restoration of WRN expression induces tumor-suppressor-like features, such as reduced colony formation density and inhibition of tumor growth in nude mouse xenograft models. Screening a large collection of human primary tumors (
n
= 630) from different cell types revealed that WRN CpG island hypermethylation was a common event in epithelial and mesenchymal tumorigenesis. Most importantly, WRN hypermethylation in colorectal tumors was a predictor of good clinical response to the camptothecin analogue irinotecan, a topoisomerase inhibitor commonly used in the clinical setting for the treatment of this tumor type. These findings highlight the importance of WRN epigenetic inactivation in human cancer, leading to enhanced chromosomal instability and hypersensitivity to chemotherapeutic drugs.
Zinc binding to a regulatory zinc-sensing domain monitored
in vivo
by using FRET
Authors: Qiao Wei , Mooney Michelle , Bird Amanda J. , Winge Dennis R. , Eide David J.
Published: May 2006

We have generated probes of metal binding to zinc fingers (ZFs) that provide tools to study zinc trafficking
in vivo
. In this study, we used these probes to examine zinc binding by the Zap1 transcription factor of
Saccharomyces cerevisiae
. Zap1 contains two zinc-regulated activation domains (ADs), AD1 and AD2. AD2 is located within two C
2
H
2
ZFs, ZF1 and ZF2. Studies have indicated that apoAD2 activates transcription and zinc binding to ZF1 and that ZF2 forms an interacting-finger-pair structure that is necessary to inhibit AD function. A related structural finger pair, ZF3 and ZF4, is found in the Zap1 DNA binding domain.
In vitro
studies indicated that, although the ZF1/2 and ZF3/4 finger pairs bind zinc with similar affinities, zinc that was bound to ZF1/2 was much more labile. We examined the properties of Zap1 ZFs
in vivo
by FRET. ZF pairs were flanked by enhanced yellow fluorescent protein and enhanced cyan fluorescent protein, allowing detection of zinc-induced conformation changes by FRET. By using these reporters, we found that ZF1/2 and ZF3/4 showed similar responses to zinc under steady-state conditions
in vivo
. In contrast, ZF1/2 zinc binding was significantly more labile than was ZF3/4. Also, ZF1/2 accumulated in an apo form that could rapidly bind zinc, whereas the ZF3/4 pair did not. Last, we show that these properties are evolutionarily conserved indicating their importance to Zap1 function. These results indicate that the kinetic lability of ZF1/2
in vivo
is a key component of Zap1 zinc responsiveness.
Modularity and community structure in networks
Authors: Newman M. E. J.
Published: May 2006

Many networks of interest in the sciences, including social networks, computer networks, and metabolic and regulatory networks, are found to divide naturally into communities or modules. The problem of detecting and characterizing this community structure is one of the outstanding issues in the study of networked systems. One highly effective approach is the optimization of the quality function known as “modularity” over the possible divisions of a network. Here I show that the modularity can be expressed in terms of the eigenvectors of a characteristic matrix for the network, which I call the modularity matrix, and that this expression leads to a spectral algorithm for community detection that returns results of demonstrably higher quality than competing methods in shorter running times. I illustrate the method with applications to several published network data sets.
Fragments of ATP synthase mediate plant perception of insect attack
Authors: Schmelz Eric A. , Carroll Mark J. , LeClere Sherry , Phipps Stephen M. , Meredith Julia , Chourey Prem S. , Alborn Hans T. , Teal Peter E. A.
Published: May 2006

Plants can perceive a wide range of biotic attackers and respond with targeted induced defenses. Specificity in plant non-self-recognition occurs either directly by perception of pest-derived elicitors or indirectly through resistance protein recognition of host targets that are inappropriately proteolyzed. Indirect plant perception can occur during interactions with pathogens, yet evidence for analogous events mediating the detection of insect herbivores remains elusive. Here we report indirect perception of herbivory in cowpea (
Vigna unguiculata
) plants attacked by fall armyworm (
Spodoptera frugiperda
) larvae. We isolated and identified a disulfide-bridged peptide (
+
ICDINGVCVDA
−
), termed inceptin, from
S. frugiperda
larval oral secretions that promotes cowpea ethylene production at 1 fmol leaf
−1
and triggers increases in the defense-related phytohormones salicylic acid and jasmonic acid. Inceptins are proteolytic fragments of chloroplastic ATP synthase γ-subunit regulatory regions that mediate plant perception of herbivory through the induction of volatile, phenylpropanoid, and protease inhibitor defenses. Only
S. frugiperda
larvae that previously ingested chloroplastic ATP synthase γ-subunit proteins and produced inceptins significantly induced cowpea defenses after herbivory. Digestive fragments of an ancient and essential plant enzyme, inceptin functions as a potent indirect signal initiating specific plant responses to insect attack.
Water properties from first principles: Simulations by a general-purpose quantum mechanical polarizable force field
Authors: Donchev A. G. , Galkin N. G. , Illarionov A. A. , Khoruzhii O. V. , Olevanov M. A. , Ozrin V. D. , Subbotin M. V. , Tarasov V. I.
Published: May 2006

We have recently introduced a quantum mechanical polarizable force field (QMPFF) fitted solely to high-level quantum mechanical data for simulations of biomolecular systems. Here, we present an improved form of the force field, QMPFF2, and apply it to simulations of liquid water. The results of the simulations show excellent agreement with a variety of experimental thermodynamic and structural data, as good or better than that provided by specialized water potentials. In particular, QMPFF2 is the only
ab initio
force field to accurately reproduce the anomalous temperature dependence of water density to our knowledge. The ability of the same force field to successfully simulate the properties of both organic molecules and water suggests it will be useful for simulations of proteins and protein–ligand interactions in the aqueous environment.
Plant-derived anti-Lewis Y mAb exhibits biological activities for efficient immunotherapy against human cancer cells
Authors: Brodzik Robert , Glogowska Magdalena , Bandurska Katarzyna , Okulicz Monika , Deka Deepali , Ko Kisung , van der Linden Joke , Leusen Jeanette H. W. , Pogrebnyak Natalia , Golovkin Maxim , Steplewski Zenon , Koprowski Hilary
Published: May 2006

Although current demands for therapeutic mAbs are growing quickly, production methods to date, includingin vitromammalian tissue culture and transgenic animals, provide only limited quantities at high cost. Several tumor-associated antigens in tumor cells have been identified as targets for therapeutic mAbs. Here we describe the production of mAb BR55-2 (IgG2a) in transgenic plants that recognizes the nonprotein tumor-associated antigen Lewis Y oligosaccharide overexpressed in human carcinomas, particularly breast and colorectal cancers. Heavy and light chains of mAb BR55-2 were expressed separately and assembled in plant cells of low-alkaloid tobacco transgenic plants (Nicotiana tabacumcv. LAMD609). Expression levels of plant-derived mAb (mAbP) were high (30 mg/kg of fresh leaves) in T1generation plants. Like the mammalian-derived mAbM, the plant mAbPbound specifically to both SK-BR3 breast cancer cells and SW948 colorectal cancer cells. The Fc domain of both mAbPand mAbMshowed the similar binding to FcγRI receptor (CD64). Comparable levels of cytotoxicity against SK-BR3 cells were also shown for both mAbs in antibody-dependent cell-mediated cytotoxicity assay. Furthermore, plant-derived BR55-2 efficiently inhibited SW948 tumor growth xenografted in nude mice. Altogether, these findings suggest that mAbPoriginating from low-alkaloid tobacco exhibit biological activities suitable for efficient immunotherapy.
The dsRNA binding site of human Toll-like receptor 3
Authors: Bell Jessica K. , Askins Janine , Hall Pamela R. , Davies David R. , Segal David M.
Published: May 2006

Pathogen recognition by Toll-like receptors (TLRs) initiates innate immune responses that are essential for inhibiting pathogen dissemination and for the development of acquired immunity. The TLRs recognize pathogens with their N-terminal ectodomains (ECD), but the molecular basis for this recognition is not known. Recently we reported the x-ray structure for unliganded TLR3-ECD; however, it has proven difficult to obtain a crystal structure of TLR3 with its ligand, dsRNA. We have now located the TLR3 ligand binding site by mutational analysis. More than 50 single-residue mutations have been generated throughout the TLR3-ECD, but only two, H539E and N541A, resulted in the loss of TLR3 activation and ligand binding functions. These mutations locate the dsRNA binding site on the glycan-free, lateral surface of TLR3 toward the C terminus and suggest a model for dsRNA binding and TLR3 activation.
Population and Policy in Marshall's Economics
Authors: Bowman Rhead S.
Published: May 2006

The Malthusian population doctrine formed an integral part of both theory and policy in classical economics: “[T]he Malthusian theory lent support to the subsistence theory of wages and prepared the way for the Ricardian preoccupation with the land-using bias of economic progress; by explaining poverty in terms of a simple race between population and the means of subsistence, it provided the touchstone for all classical thinking about economic policy” (Blaug 1997, p. 65). Among historians of economic thought there is probably little in this statement with which to disagree. A variety of interpretations, however, have been given to the subsequent career of the population doctrine, including its place in the economics of Alfred Marshall. Economists after John Stuart Mill, Joseph Schumpeter argued, found the population doctrine to be of little theoretical use to economics: many leading economists of the neoclassical school, including Alfred Marshall, “paid their respects to it, even though they no longer based upon it any part of their analytic structures” (1954, p. 890). Mark Blaug, by contrast, suggests that the analysis of population in Marshall's Principles of Economics indicates an “orthodox classical attitude to population problems” (1997, p. 385). Yet another perspective is offered by John Whitaker who remarks that early in his career Marshall resolved to transform the “old political economy into a new science of economics, open to the progressive intellectual and social movements of the day.” His intent was to leave behind the sterile controversies and pessimistic pronouncements of the old political economy, including those associated with the population doctrine (1996, vol. 1, pp. xvii, xx).
James M. Buchanan and Edmund Burke: Opposite Sides of the Same Fiscal Constitution Coin
Authors: Considine John
Published: May 2006

Constitutional economics examines the individual's choice-between-rules rather than their choice-within-rules. It is, according to James M. Buchanan, a restatement of the classical political economy of Adam Smith. One of its primary normative implications is the need for a fiscal constitution. Given the late eighteenth century intellectual basis for such fiscal constitutions it appears, at first glance, a little strange that the research program does not consider Edmund Burke's 1780 economic constitution worthy of consideration. The most obvious reason for Burke's exclusion from constitutional political economy is that the methodological basis of Buchanan's twentieth century constitutional economics seems almost the polar opposite of Burke's eighteenth century legislator's attempt to introduce a fiscal constitution. However, both methodologies suffer from internal inconsistency in their cases for a fiscal constitution. One of the primary reasons for this inconsistency is that each needs to appeal to ideas more at home in the methodology of the other. Buchanan adapts a quasi-Burke approach by the introduction of ethical norms not consistent with the self-interest postulate, while Burke adopts a quasi-Buchanan approach by appealing to the principle of consent to justify his reform of institutions that have been formed by custom and tradition. Ultimately, the methodological difference is not as great as it appears at first. The purpose of this paper is to demonstrate that Burke's work deserves recognition in the broader constitutional economics research program because to exclude him on the grounds of methodology is to fail to understand the logical implications of Buchanan's work.
Woodford and Wicksell on Interest and Prices: The Place of the Pure Credit Economy in the Theory of Monetary Policy
Authors: Laidler David
Published: May 2006

There can be no doubt that the monetary systems of a number of advanced countries nowadays resemble Knut Wicksell's (1898) model of the “pure credit economy” much more closely than did any that actually existed in the world for which he wrote. Currency has long been losing its quantitative importance in mediating transactions among the general public in such countries, and more recently, the development of modern information technology has made it possible for them to operate the clearing and settlement systems that underpin the use of bank deposits as means of exchange with a close-to-zero stock of reserve assets.
Spectra of algebras of entire functions on Banach spaces
Authors: Zagorodnyuk Andriy
Published: May 2006

We obtain an explicit description of the spectrum (set of closed maximal ideals) of

H
b

(
X
)
,

H_b(X),

algebra of analytic functions on a Banach space

X
X

which are bounded on bounded subsets. We show that the spectrum of

H
b

(
X
)

H_b(X)

admits a natural linear structure. Some applications to the algebra of uniformly continuous and bounded analytic functions on the unit ball

B
⊂
X

B\subset X

are indicated.
Deformations and derived equivalences
Authors: Bleher Frauke
Published: May 2006

Suppose

A
A

and

B
B

are block algebras of finite groups over a complete local commutative Noetherian ring whose residue field is a field

k
k

of positive characteristic. We prove that a split-endomorphism two-sided tilting complex (as introduced by Rickard) for the derived categories of bounded complexes of finitely generated modules over

A
A

, resp.

B
B

, preserves the versal deformation rings of bounded complexes of finitely generated modules over

k
A

kA

, resp.

k
B

kB

.
Gaugeability for Feynman-Kac functionals with applications to symmetric 𝛼-stable processes
Authors: Takeda Masayoshi
Published: May 2006

For symmetric

α
\alpha

-stable processes, an analytic criterion for a measure being gaugeable was obtained by Z.-Q. Chen (2002), M. Takeda (2002) and M. Takeda and T. Uemura (2004). Applying it, we consider the ultracontractivity of Feynman-Kac semigroups and expectations of the number of branches hitting closed sets in branching symmetric

α
\alpha

-stable processes.
An invariant for unbounded operators
Authors: Manuilov Vladimir , Silvestrov Sergei
Published: May 2006

For a class of unbounded operators, a deformation of a Bott projection is used to construct an integer-valued invariant measuring deviation of the non-commutative deformations from the commutative originals, and its interpretation in terms of

K
K

-theory of

C
∗

C^*

-algebras is given. Calculation of this invariant for specific important classes of unbounded operators is also presented.
Scaled-oscillation and regularity
Authors: Balogh Zoltán , Csörnyei Marianna
Published: May 2006

We give sufficient conditions for Sobolev and Lipschitz functions in terms of their lower scaled-oscillation. The sharpness of these conditions is shown by examples. Our examples also show that a Stepanov-type differentiability theorem does not hold under the boundedness assumption of the lower scaled-oscillation.
Convergence of weighted averages of random variables revisited
Authors: Etemadi Nasrollah
Published: May 2006

We show that for a large class of positive weights including the ones that are eventually monotone decreasing and those that are eventually monotone increasing but vary regularly, if the averages of random variables converge in some sense, then their corresponding weighted averages also converge in the same sense. We will also replace the sufficient conditions in the fundamental result of Jamison, Pruitt, and Orey for i.i.d. random variables that make their work more transparent.
Some applications of Ball’s extension theorem
Authors: Mendel Manor , Naor Assaf
Published: May 2006

We present two applications of Ball’s extension theorem. First we observe that Ball’s extension theorem, together with the recent solution of Ball’s Markov type

2
2

problem due to Naor, Peres, Schramm and Sheffield, imply a generalization, and an alternative proof of, the Johnson-Lindenstrauss extension theorem. Second, we prove that the distortion required to embed the integer lattice

{
0
,
1
,
…
,
m

}
n

\{0,1,\ldots ,m\}^n

, equipped with the

ℓ
p
n

\ell _p^n

metric, in any

2
2

-uniformly convex Banach space is of order

min

{

n

1
2

−

1
p

,

m

1
−

2
p

}

\min \left \{n^{\frac 12-\frac {1}{p}},m^{1-\frac {2}{p}}\right \}

.
The Banach algebra generated by a contraction
Authors: Mustafayev H.
Published: May 2006

Let

T
T

be a contraction on a Banach space and

A

T

A_{T}

the Banach algebra generated by

T
T

. Let

σ

u

(
T
)

\sigma _{u}(T)

be the unitary spectrum (i.e., the intersection of

σ
(
T
)

\sigma (T)

with the unit circle) of

T
T

. We prove the following theorem of Katznelson-Tzafriri type: If

σ

u

(
T
)

\sigma _{u}(T)

is at most countable, then the Gelfand transform of

R
∈

A

T

R\in A_{T}

vanishes on

σ

u

(
T
)

\sigma _{u}(T)

if and only if

lim

n
→
∞

‖

T

n

R
‖

=
0.

\lim _{n\rightarrow \infty }\left \Vert T^{n}R\right \Vert =0.
A generalization of Andô’s theorem and Parrott’s example
Authors: Opěla David
Published: May 2006

Andô’s theorem states that any pair of commuting contractions on a Hilbert space can be dilated to a pair of commuting unitaries. Parrott presented an example showing that an analogous result does not hold for a triple of pairwise commuting contractions. We generalize both of these results as follows. Any

n
n

-tuple of contractions that commute according to a graph without a cycle can be dilated to an

n
n

-tuple of unitaries that commute according to that graph. Conversely, if the graph contains a cycle, we construct a counterexample.
Existence of positive solutions for a semilinear elliptic problem with critical Sobolev and Hardy terms
Authors: Hirano Norimichi , Shioji Naoki
Published: May 2006

Let

N
≥
4

N\geq 4

, let

2

∗

=
2
N

/

(
N
−
2
)

2^{\ast }=2N/(N-2)

and let

Ω
⊂

R

N

\Omega \subset \mathbb {R}^{N}

be a bounded domain with a smooth boundary

∂
Ω

\partial \Omega

. Our purpose in this paper is to consider the existence of solutions of the problem:
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartLayout Enlarged left-brace 1st Row 1st Column minus normal upper Delta u minus mu StartFraction u Over StartAbsoluteValue x EndAbsoluteValue squared EndFraction 2nd Column a m p semicolon equals StartAbsoluteValue u EndAbsoluteValue Superscript 2 Super Superscript asterisk Superscript minus 1 Baseline 3rd Column a m p semicolon 4th Column a m p semicolon in normal upper Omega comma 2nd Row 1st Column u 2nd Column a m p semicolon greater-than 0 3rd Column a m p semicolon 4th Column a m p semicolon in normal upper Omega comma 3rd Row 1st Column u 2nd Column a m p semicolon equals 0 3rd Column a m p semicolon 4th Column a m p semicolon on partial-differential normal upper Omega comma EndLayout">

{

−
Δ
u
−
μ

u

|
x

|
2

a
m
p
;
=
|
u

|

2
∗

−
1

a
m
p
;

a
m
p
;

in 

Ω

,

u

a
m
p
;
>
0

a
m
p
;

a
m
p
;

in 

Ω

,

u

a
m
p
;
=
0

a
m
p
;

a
m
p
;

on 

∂
Ω

,

\left \{ \begin {aligned} -\Delta u - \mu \frac {u}{\vert x\vert ^2} &= \vert u\vert ^{2^\ast -1} && \text {in $\Omega $}, \\ u & > 0 && \text {in $\Omega $},\\ u & = 0 && \text {on $\partial \Omega $}, \end {aligned} \right .

\]
where

0
>
μ
>
(

N
−
2

2

)

2

.

0>\mu >(\frac {N-2}{2})^{2}.
Hodge structures for orbifold cohomology
Authors: Fernandez Javier
Published: May 2006

We construct a polarized Hodge structure on the primitive part of Chen and Ruan’s orbifold cohomology

H

o
r
b

k

(
X
)

H_{orb}^k(X)

for projective

S
L

SL

-orbifolds

X
X

satisfying a “Hard Lefschetz Condition”. Furthermore, the total cohomology

⨁

p
,
q

H

o
r
b

p
,
q

(
X
)

\bigoplus _{p,q}H_{orb}^{p,q}(X)

forms a mixed Hodge structure that is polarized by every element of the Kähler cone of

X
X

. Using results of Cattani-Kaplan-Schmid this implies the existence of an abstract polarized variation of Hodge structure on the complexified Kähler cone of

X
X

. This construction should be considered as the analogue of the abstract polarized variation of Hodge structure that can be attached to the singular cohomology of a crepant resolution of

X
X

, in light of the conjectural correspondence between the (quantum) orbifold cohomology and the (quantum) cohomology of a crepant resolution.
A quasifibration of spaces of positive scalar curvature metrics
Authors: Chernysh Vladislav
Published: May 2006

In this paper we show that for Riemannian manifolds with boundary the natural restriction map is a quasifibration between spaces of metrics of positive scalar curvature. We apply this result to study homotopy properties of spaces of such metrics on manifolds with boundary.
A remark on the existence of suitable vector fields related to the dynamics of scalar semi-linear parabolic equations
Authors: Hang Fengbo , Jiang Huiqiang
Published: May 2006

In 1992, P. Poláčik showed that one could linearly imbed any vector field into a scalar semi-linear parabolic equation on

Ω
\Omega

with Neumann boundary condition provided that there exists a smooth vector field

Φ
=

(

ϕ

1

,
⋯
,

ϕ

n

)

\Phi =\left ( \phi _{1},\cdots ,\phi _{n}\right )

on

Ω
¯

\overline {\Omega }

such that
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartLayout Enlarged left-brace 1st Row r a n k left-parenthesis normal upper Phi left-parenthesis x right-parenthesis comma partial-differential Subscript 1 Baseline normal upper Phi left-parenthesis x right-parenthesis comma midline-horizontal-ellipsis comma partial-differential Subscript n Baseline normal upper Phi left-parenthesis x right-parenthesis right-parenthesis equals n for all x element-of normal upper Omega overbar comma StartFraction partial-differential normal upper Phi Over partial-differential nu EndFraction equals 0 on partial-differential normal upper Omega period EndLayout">

{

rank
⁡

(
Φ

(
x
)

,

∂

1

Φ

(
x
)

,
⋯
,

∂

n

Φ

(
x
)

)

=
n
 for all 
x
∈

Ω
¯

,

∂
Φ

∂
ν

=
0
 on 
∂
Ω
.

\left \{ \begin {array} [c]{l} \operatorname {rank}\left ( \Phi \left ( x\right ) ,\partial _{1}\Phi \left ( x\right ) ,\cdots ,\partial _{n}\Phi \left ( x\right ) \right ) =n\text { for all }x\in \overline {\Omega }, \frac {\partial \Phi }{\partial \nu }=0\text { on }\partial \Omega \text {.} \end {array} \right .

\]
In this short paper, we give a classification of all the domains on which one may find such a type of vector field.
On the arithmetic of tight closure
Authors: Brenner Holger , Katzman Mordechai
Published: May 2006

We provide a negative answer to an old question in tight closure theory by showing that the containment

x
3

y
3

∈
(

x
4

,

y
4

,

z
4

)
∗

x^3y^3 \in (x^4,y^4,z^4)^*

in

K

[
x
,
y
,
z
]

/

(

x
7

+

y
7

−

z
7

)

\mathbb {K}[x,y,z]/(x^7+y^7-z^7)

holds for infinitely many but not for almost all prime characteristics of the field

K

\mathbb {K}

. This proves that tight closure exhibits a strong dependence on the arithmetic of the prime characteristic. The ideal
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="left-parenthesis x comma y comma z right-parenthesis subset-of double-struck upper K left-bracket x comma y comma z comma u comma v comma w right-bracket slash left-parenthesis x Superscript 7 Baseline plus y Superscript 7 Baseline minus z Superscript 7 Baseline comma u x Superscript 4 Baseline plus v y Superscript 4 Baseline plus w z Superscript 4 Baseline plus x cubed y cubed right-parenthesis">

(
x
,
y
,
z
)
⊂

K

[
x
,
y
,
z
,
u
,
v
,
w
]

/

(

x
7

+

y
7

−

z
7

,
u

x
4

+
v

y
4

+
w

z
4

+

x
3

y
3

)

(x,y,z) \subset \mathbb {K}[x,y,z,u,v,w]/(x^7+y^7-z^7, ux^4+vy^4+wz^4+x^3y^3)

has then the property that the cohomological dimension fluctuates arithmetically between

0
0

and

1
1

.
A new tower of Rankin-Selberg integrals
Authors: Ginzburg David , Hundley Joseph
Published: May 2006

We recall the notion of a tower of Rankin-Selberg integrals, and two known towers, making observations of how the integrals within a tower may be related to one another via formal manipulations, and offering a heuristic for how the

L
L

-functions should be related to one another when the integrals are related in this way. We then describe three new integrals in a tower on the group

E
6

,

E_6,

and find out which

L
L

-functions they represent. The heuristics also predict the existence of a fourth integral.
Cobounding odd cycle colorings
Authors: Kozlov Dmitry
Published: May 2006

We prove that the

(
n
−
2
)

(n-2)

nd power of the Stiefel-Whitney class of the space of all

n
n

-colorings of an odd cycle is 

0
0

by presenting a cochain whose coboundary is the desired power of the class. This gives a very short self-contained combinatorial proof of a conjecture by Babson and the author.
LRRC4, a Putative Tumor Suppressor Gene, Requires a Functional Leucine-rich Repeat Cassette Domain to Inhibit Proliferation of Glioma Cells In Vitro by Modulating the Extracellular Signal-regulated Kinase/Protein Kinase B/Nuclear Factor-κB Pathway
Authors: Wu Minghua , Huang Chen , Gan Kai , Huang He , Chen Qiong , Ouyang Jue , Tang Yunlian , Li Xiaoling , Yang Yixin , Zhou Houde , Zhou Yanhong , Zeng Zhaoyang , Xiao Lan , Li Dan , Tang Ke , Shen Shourong , Li Guiyuan
Published: May 2006

We have previously reported that the LRRC4 gene, which contains a conserved leucine-rich repeat (LRR) cassette and an immunoglobulin (Ig) IgC2 domain, is associated with glioma suppression both in vitro and in vivo. The present study provides evidence that the conspicuous absence of LRRC4 in high-grade gliomas directly contributes to the increasing tumor grade. The loss of LRRC4 in U251 cells is caused by the loss of homozygosity at chromosome 7q32-ter. It was also found that LRRC4 requires a functional LRR cassette domain to suppress U251 cell proliferation. In the LRR cassette domain, the third LRR motif of the core LRR is found to be indispensable for the function of LRRC4. The inhibitory effect of LRRC4 is accompanied by a decrease in the expression of pERK, pAkt, pNF-κBp65, signal transducer and activator of transcription protein-3 (STAT3), and mutant p53, and an increase in the expression of c-Jun NH2-terminal kinase (JNK)2 and p-c-Jun, suggesting that LRRC4 plays a major role in suppressing U251 cell proliferation by regulating the extracellular signal-regulated kinase (ERK)/Akt/NF-κBp65, STAT3, and JNK2/c-Jun pathways. In conclusion, LRRC4 may act as a novel candidate of tumor suppressor gene. Therefore, the loss of LRRC4 function may be an important event in the progression of gliomas.
Activation of Casein Kinase II and Inhibition of Phosphatase and Tensin Homologue Deleted on Chromosome 10 Phosphatase by Nerve Growth Factor/p75NTRInhibit Glycogen Synthase Kinase-3β and Stimulate Axonal Growth
Authors: Arevalo María-Angeles , Rodríguez-Tébar Alfredo
Published: May 2006

Axonal elongation and guidance are controlled by extracellular factors such as the neurotrophins. Indeed, nerve growth factor (NGF) seems to promote axon growth through binding to its p75NTRreceptor and inactivating RhoA. Furthermore, the local inhibition of glycogen synthase kinase (GSK)-3β by NGF also favors microtubule polymerization and axon extension. Inactivation of GSK-3β may be due to the NGF/TrkA-mediated activation of phosphatidylinositol-3 kinase (PI-3 kinase), which increases the levels of phosphatydilinositol 3-phosphate [PI(3)P]. However, we show here that NGF may inactivate GSK-3β through an alternative mechanism. In cultured hippocampal neurons, the capacity of NGF to promote axon elongation is mostly mediated by p75NTR, and the activation of this pathway leads to the inactivation of GSK-3β. However, the signaling pathway triggered by NGF/p75NTRacts through casein kinase II (CK2). NGF/p75NTR-activated CK2 phosphorylates the phosphatase and tensin homologue deleted on chromosome 10 (PTEN), thus rendering this phosphatase inactive. Like activation of the PI-3 kinase, PTEN inactivation allows PI(3)P levels to increase, thus favoring GSK-3β inactivation and axon outgrowth. This newly disclosed mechanism may help to extend the repertoire of pharmacological agents that activate CK2 or that inhibit PTEN to stimulate axon regeneration after trauma or disease.
Efficient Trafficking of MDR1/P-Glycoprotein to Apical Canalicular Plasma Membranes in HepG2 Cells Requires PKA-RIIα Anchoring and Glucosylceramide
Authors: Wojtal Kacper A. , de Vries Erik , Hoekstra Dick , van IJzendoorn Sven C.D.
Published: May 2006

In hepatocytes, cAMP/PKA activity stimulates the exocytic insertion of apical proteins and lipids and the biogenesis of bile canalicular plasma membranes. Here, we show that the displacement of PKA-RIIα from the Golgi apparatus severely delays the trafficking of the bile canalicular protein MDR1 (P-glycoprotein), but not that of MRP2 (cMOAT), DPP IV and 5′NT, to newly formed apical surfaces. In addition, the direct trafficking of de novo synthesized glycosphingolipid analogues from the Golgi apparatus to the apical surface is inhibited. Instead, newly synthesized glucosylceramide analogues are rerouted to the basolateral surface via a vesicular pathway, from where they are subsequently endocytosed and delivered to the apical surface via transcytosis. Treatment of HepG2 cells with the glucosylceramide synthase inhibitor PDMP delays the appearance of MDR1, but not MRP2, DPP IV, and 5′NT at newly formed apical surfaces, implicating glucosylceramide synthesis as an important parameter for the efficient Golgi-to-apical surface transport of MDR1. Neither PKA-RIIα displacement nor PDMP inhibited (cAMP-stimulated) apical plasma membrane biogenesis per se, suggesting that other cAMP effectors may play a role in canalicular development. Taken together, our data implicate the involvement of PKA-RIIα anchoring in the efficient direct apical targeting of distinct proteins and glycosphingolipids to newly formed apical plasma membrane domains and suggest that rerouting of Golgi-derived glycosphingolipids may underlie the delayed Golgi-to-apical surface transport of MDR1.
BDT: an easy-to-use front-end application for automation of massive docking tasks and complex docking strategies with AutoDock
Authors: Vaqué Montserrat , Arola Anna , Aliagas Carles , Pujadas Gerard
Published: May 2006

Motivation: AutoGrid/AutoDock is one of the most popular software packages for docking, but its automation is not trivial for tasks such as (1) the virtual screening of a library of ligands against a set of possible receptors; (2) the use of receptor flexibility and (3) making a blind-docking experiment with the whole receptor surface. This is an obstacle for research teams in the fields of Chemistry and the Life Sciences who are interested in conducting this kind of experiment but do not have enough programming skills. To overcome these limitations, we have designed BDT, an easy-to-use graphic interface for AutoGrid/AutoDock.

Availability: BDT is available for free, upon request, for non-commercial research.

Supplementary information:  

Contact:  gerard.pujadas@urv.cat
Imprint of evolutionary conservation and protein structure variation on the binding function of protein tyrosine kinases
Authors: Verkhivker Gennady M.
Published: May 2006

Motivation: According to the models of divergent molecular evolution, the evolvability of new protein function may depend on the induction of new phenotypic traits by a small number of mutations of the binding site residues. Evolutionary relationships between protein kinases are often employed to infer inhibitor binding profiles from sequence analysis. However, protein kinases binding profiles may display inhibitor selectivity within a given kinase subfamily, while exhibiting cross-activity between kinases that are phylogenetically remote from the prime target. The emerging insights into kinase function and evolution combined with a rapidly growing number of publically available crystal structures of protein kinases complexes have motivated structural bioinformatics analysis of sequence–structure relationships in determining the binding function of protein tyrosine kinases.

Results:  In silico profiling of Imatinib mesylate and PD-173955 kinase inhibitors with protein tyrosine kinases is conducted on kinome scale by using evolutionary analysis and fingerprinting inhibitor–protein interactions with the panel of all publically available protein tyrosine kinases crystal structures. We have found that sequence plasticity of the binding site residues alone may not be sufficient to enable protein tyrosine kinases to readily evolve novel binding activities with inhibitors. While evolutionary signal derived solely from the tyrosine kinase sequence conservation can not be readily translated into the ligand binding phenotype, the proposed structural bioinformatics analysis can discriminate a functionally relevant kinase binding signal from a simple phylogenetic relationship. The results of this work reveal that protein conformational diversity is intimately linked with sequence plasticity of the binding site residues in achieving functional adaptability of protein kinases towards specific drug binding. This study offers a plausible molecular rationale to the experimental binding profiles of the studied kinase inhibitors and provides a theoretical basis for constructing functionally relevant kinase binding trees.

Contact:  gverkhiv@ucsd.edu

Supplementary information: The supplementary material contains the details of the phylogenetic analysis of protein tyrosine kinases, including phylogenetic dendrograms of protein tyrosine kinases based on sequence alignments of the kinases catalytic domain and evolutionary conservation profiles of the binding site residues. This section provides a more detailed description of the Monte Carlo binding simulations, including energetic model and simulated tempering technique generalized for ligand–protein binding dynamics with the multiple protein tyrosine kinase structures.
SNPStats: a web tool for the analysis of association studies
Authors: Solé Xavier , Guinó Elisabet , Valls Joan , Iniesta Raquel , Moreno Víctor
Published: May 2006

Summary: A web-based application has been designed from a genetic epidemiology point of view to analyze association studies. Main capabilities include descriptive analysis, test for Hardy–Weinberg equilibrium and linkage disequilibrium. Analysis of association is based on linear or logistic regression according to the response variable (quantitative or binary disease status, respectively). Analysis of single SNPs: multiple inheritance models (co-dominant, dominant, recessive, over-dominant and log-additive), and analysis of interactions (gene–gene or gene–environment). Analysis of multiple SNPs: haplotype frequency estimation, analysis of association of haplotypes with the response, including analysis of interactions.

Availability:  . Source code for local installation is available under GNU license.

Contact:  v.moreno@iconcologia.net

Supplementary Information: Figures with a sample run are available on Bioinformatics online. A detailed online tutorial is available within the application.
Fructose Administration Increases Intraoperative Core Temperature by Augmenting Both Metabolic Rate and the Vasoconstriction Threshold
Authors: Mizobe Toshiki , Nakajima Yasufumi , Ueno Hiroshi , Sessler Daniel I.
Published: May 2006

Background

The authors tested the hypothesis that intravenous fructose ameliorates intraoperative hypothermia both by increasing metabolic rate and the vasoconstriction threshold (triggering core temperature).

Methods

Forty patients scheduled to undergo open abdominal surgery were divided into two equal groups and randomly assigned to intravenous fructose infusion (0.5 g . kg(-1) . h(-1) for 4 h, starting 3 h before induction of anesthesia and continuing for 4 h) or an equal volume of saline. Each treatment group was subdivided: Esophageal core temperature, thermoregulatory vasoconstriction, and plasma concentrations were determined in half, and oxygen consumption was determined in the remainder. Patients were monitored for 3 h after induction of anesthesia.

Results

Patient characteristics, anesthetic management, and circulatory data were similar in the four groups. Mean final core temperature (3 h after induction of anesthesia) was 35.7 degrees +/- 0.4 degrees C (mean +/- SD) in the fructose group and 35.1 degrees +/- 0.4 degrees C in the saline group (P = 0.001). The vasoconstriction threshold was greater in the fructose group (36.2 degrees +/- 0.3 degrees C) than in the saline group (35.6 degrees +/- 0.3 degrees C; P < 0.001). Oxygen consumption immediately before anesthesia induction in the fructose group (214 +/- 18 ml/min) was significantly greater than in the saline group (181 +/- 8 ml/min; P < 0.001). Oxygen consumption was 4.0 l greater in the fructose patients during 3 h of anesthesia; the predicted difference in mean body temperature based only on the difference in metabolic rates was thus only 0.4 degrees C. Epinephrine, norepinephrine, and angiotensin II concentrations and plasma renin activity were similar in each treatment group.

Conclusions

Preoperative fructose infusion helped to maintain normothermia by augmenting both metabolic heat production and increasing the vasoconstriction threshold.
Comparison of Three Disposable Extraglottic Airway Devices in Spontaneously Breathing Adults
Authors: van Zundert André , Al-Shaikh Baha , Brimacombe Joseph , Koster Jurgen , Koning Dick , Mortier Eric P.
Published: May 2006

Background

The authors compared three disposable extraglottic airway devices in spontaneously breathing anesthetized adults: the LMA-Unique (LMA-U; The Laryngeal Mask Company, San Diego, CA), the Soft Seal laryngeal mask (SS-LM; Portex Ltd., Hythe, United Kingdom), and the Cobra perilaryngeal airway (Cobra-PLA; Engineered Medical Systems, Inc. Indianapolis, IN).

Methods

Three hundred twenty consecutive adults (American Society of Anesthesiologists physical status I-III; aged 18-80 yr) were randomly allocated for airway management with one of the three devices. Anesthesia was with fentanyl-propofol for induction and a sevoflurane-nitrous oxide-oxygen-fentanyl mixture for maintenance. Intraoperative data were collected by an unblinded observer about ease of insertion, effective airway time, oropharyngeal leak pressure, anatomical position (determined with a rigid endoscope), intracuff pressure changes, and airway trauma. Data were collected by a blinded observer about sore throat, dysphagia, and dysphonia 2 h after surgery.

Results

Insertion was easier with the LMA-U and SS-LM than with the Cobra-PLA (P < 0.02), but the overall failure rates were similar. Effective airway times were similar among groups. Oropharyngeal leak pressure was lower with the LMA-U than with the SS-LM and Cobra-PLA (P < 0.001). Intracuff pressure increased during surgery with all extraglottic airway devices. Anatomical position was better with the Cobra-PLA than with the SS-LMA (P < 0.001) and better with the SS-LM than with LMA-U (P < 0.001). Blood staining was detected more frequently with the Cobra-PLA than with the LMA-U and SS-LM (P < 0.001), but there were no differences in airway morbidity.

Conclusion

The LMA-U and SS-LM are easier to insert and cause less trauma than the Cobra-PLA, but the Cobra-PLA has a more effective seal than the LMA-U and better endoscopically determined anatomical position than the LMA-U and SS-LM.
Additive Effects of Sevoflurane and Propofol on γ-Aminobutyric Acid Receptor Function
Authors: Sebel Luke E. , Richardson James E. , Singh Sunil P. , Bell Shannon V. , Jenkins Andrew
Published: May 2006

Background

Previous studies have shown that propofol and sevoflurane enhance the function of gamma-aminobutyric acid type A (GABAA) receptors. However, it is not known whether these two drugs modulate the same molecular pathways. In addition, little is known about receptor function in the presence of both propofol and sevoflurane. The aim of this study was to better understand the interactions of propofol and sevoflurane with the GABAA receptor.

Methods

Wild-type alpha1, beta(2), gamma(2s) GABA(A) receptor subunit complementary DNAs were transfected into human embryonic kidney cells grown on glass coverslips using a calcium phosphate transfection method. After transfection (36-72 h), cells were whole cell patch clamped and exposed to combinations of the following: 0.3-1,000 microm gamma-aminobutyric acid (GABA), 0-10 microm propofol, and 0-1,650 microm sevoflurane. Chemicals were delivered to the cells using two 10-channel infusion pumps and a rapid solution exchanger.

Results

Both propofol and sevoflurane alone enhanced the amplitude of GABA(A) receptor responses to submaximal concentrations of GABA in a dose-dependent manner. The enhancement was underpinned by an increase in the apparent affinity of the receptor for GABA. Coapplication of both anesthetics further enhanced the apparent affinity of the receptor for GABA.

Conclusions

Response surface modeling of the potentiation of GABA responses (0.3-1,000 microm) by sevoflurane and propofol revealed that the two anesthetics modulated receptor function in an additive manner. These results are consistent with recent mutagenesis studies, suggesting that these two drugs have separate binding sites and converging pathways of action on the GABAA receptor.