bluuebunny/crossref_metadata_2025 huggingface dataset:
Osmotically induced synthesis of the dipeptide N-acetylglutaminylglutamine amide is mediated by a new pathway conserved among bacteria
Authors: Sagot Brice , Gaysinski Marc , Mehiri Mohamed , Guigonis Jean-Marie , Le Rudulier Daniel , Alloing Geneviève
Published: June 2010

The dipeptide N-acetylglutaminylglutamine amide (NAGGN) was discovered in the bacterium
Sinorhizobium meliloti
grown at high osmolarity, and subsequently shown to be synthesized and accumulated by a few osmotically challenged bacteria. However, its biosynthetic pathway remained unknown. Recently, two genes, which putatively encode a glutamine amidotransferase and an acetyltransferase and are up-regulated by osmotic stress, were identified in
Pseudomonas aeruginosa
. In this work, a locus carrying the orthologous genes in
S. meliloti
,
asnO and ngg
, was identified, and the genetic and molecular characterization of the NAGGN biosynthetic pathway is reported. By using NMR experiments, it was found that strains inactivated in
asnO
and
ngg
were unable to produce the dipeptide. Such inability has a deleterious effect on
S. meliloti
growth at high osmolarity, demonstrating the key role of NAGGN biosynthesis in cell osmoprotection. β-Glucuronidase activity from transcriptional fusion revealed strong induction of
asnO
expression in cells grown in increased NaCl concentration, in good agreement with the NAGGN accumulation. The
asnO
–
ngg
cluster encodes a unique enzymatic machinery mediating nonribosomal peptide synthesis. This pathway first involves Ngg, a bifunctional enzyme that catalyzes the formation of the intermediate N-acetylglutaminylglutamine, and second AsnO, required for subsequent addition of an amide group and the conversion of N-acetylglutaminylglutamine into NAGGN. Interestingly, a strong conservation of the
asnO
–
ngg
cluster is observed in a large number of bacteria with different lifestyles, such as marine, symbiotic, and pathogenic bacteria, highlighting the ecological importance of NAGGN synthesis capability in osmoprotection and also potentially in bacteria host–cell interactions.
The colony of the colonized: the Duchy of Courland's Tobago colony and contemporary Latvian national identity
Authors: Merritt Harry C.
Published: June 2010

This paper examines the legacy of the Duchy of Courland's overseas colony of Tobago as it relates to present-day Latvian national identity using the ethno-symbolist approach of Anthony D. Smith and comparative cases. As Latvia is a small nation that has been an independent nation-state for only two short periods, national legitimacy and pride pose particular problems for Latvians. To this end, Latvian historians have worked to reinterpret the Baltic German-dominated Duchy of Courland as a positive period of Latvian national history and have sought to emphasize ethnic Latvian involvement in the Duchy's colonial endeavors, especially on the island of Tobago. Their efforts have then filtered into the general Latvian consciousness through books, film, plays, and place names. Since Latvia's independence from the USSR, the former colony of Tobago has gained renewed importance for Latvians who are experiencing a widely perceived notion of postcolonialism. This paper concludes that the appropriated colony of Tobago will continue to rise in importance as a component of Latvian national identity.
ARE GREEN POLITICAL PARTIES MORE POST-MATERIALIST THAN OTHER PARTIES?
Authors: Belchior Ana Maria
Published: June 2010

Among other social and political changes, post-materialist theory anticipated the need to strengthen democracy in political institutions in post-industrial societies. This change in political values would mean that in addition to growth in post-materialist values, parties would be pushed to take an alternative view of politics that would entail greater assimilation of democratic procedures. This paper partially and empirically tests the validity of this explanation in four European party systems. The Greens are the focus, since they are considered the parties that best fit the post-materialist profile. In particular, the paper aims to ascertain whether the Greens display a significantly better positioning in respect to support for democracy and the congruence of their voters than other parties, as theory leads us to believe. The explanation of higher levels of party congruence is also expected to be related to post-materialist party features. The findings of this research did not show enough evidence to validate our theoretical expectations.
Electron, ion and vacuum ultraviolet photon effects in 193 nm photoresist surface roughening
Authors: Chung T-Y , Nest D , Graves D B , Weilnboeck F , Bruce R L , Oehrlein G S , Wang D , Li M , Hudson E A
Published: June 2010

Low temperature plasma exposure of methacrylate-based 193 nm photoresist (PR) can result in enhanced surface roughening or smoothing, but mechanisms are poorly understood. We present measurements of 193 nm PR surface roughness following exposure to 1 keV electron beams in various combinations with positive ion and vacuum ultraviolet (VUV) photon irradiation. Electron beams will scission or cross-link 193 nm PR under low and high fluence exposure, respectively. When coupled to simultaneous ion/VUV photon irradiation, low fluence (scissioning) electrons amplify surface roughening while high fluence (cross-linking) electrons reduce surface roughness. These results further suggest that enhanced roughening of 193 nm PR is initiated by the synergistic interaction between an ion bombardment-induced carbon-rich surface layer (∼2 nm) and a sicssioned bulk layer (∼100 nm).
Semiconductors for terahertz photonics applications
Authors: Krotkus Arūnas
Published: June 2010

Generation and measurement of ultrashort, subpicosecond pulses of electromagnetic radiation with their characteristic Fourier spectra that reach far into terahertz (THz) frequency range has recently become a versatile tool of far-infrared spectroscopy and imaging. This technique, THz time-domain spectroscopy, in addition to a femtosecond pulse laser, requires semiconductor components manufactured from materials with a short photoexcited carrier lifetime, high carrier mobility and large dark resistivity. Here we will review the most important developments in the field of investigation of such materials. The main characteristics of low-temperature-grown or ion-implanted GaAs and semiconducting compounds sensitive in the wavelength ranges around 1 µm and 1.5 µm will be surveyed. The second part of the paper is devoted to the effect of surface emission of THz transients from semiconductors illuminated by femtosecond laser pulses. The main physical mechanisms leading to this emission as well as their manifestation in various crystals will be described.
Boron carbide based solid state neutron detectors: the effects of bias and time constant on detection efficiency
Authors: Hong Nina , Mullins John , Foreman Keith , Adenwalla S
Published: June 2010

Neutron detection in thick boron carbide(BC)/n-type Si heterojunction diodes shows a threefold increase in efficiency with applied bias and longer time constants. The improved efficiencies resulting from long time constants have been conclusively linked to the much longer charge collection times in the BC layer. Neutron detection signals from both the p-type BC layer and the n-type Si side of the heterojunction diode are observed, with comparable efficiencies. Collectively, these provide strong evidence that the semiconducting BC layer plays an active role in neutron detection, both in neutron capture and in charge generation and collection.
Discharge characteristics of a nano-sized electrode with aligned carbon nanotubes grown on a tungsten whisker tip under various gas conditions
Authors: Liang Bo , Ogino Akihisa , Nagatsu Masaaki
Published: June 2010

Vertically aligned multiwalled carbon nanotubes (CNTs) were grown on a tungsten (W) tip by thermal chemical vapour deposition, applying a negative biasing voltage to the W tip in a pin–plate electrode configuration. The CNT electrodes, due to their nano-sized tip radii, create very high electric fields, and reduce the breakdown voltage significantly. Comparing the CNTs-grown W tip electrode with the W tip electrode, the ignition voltage for the former case decreased from 230 to 181 V, while the saturation current increased from 12 to 20 µA. These results are attributed to a relatively high field enhancement factor β ∼ 960 of the CNTs electrodes compared with β ∼ 60 for the simple W tip. There are also significant differences between the W tip electrodes with and without CNTs in the values of the igniting voltage and discharge current, when the W tips are used as a cathode.
Synthesis and systematic characterization of functionalized graphene sheets generated by thermal exfoliation at low temperature
Authors: Jin Meihua , Jeong Hae-Kyung , Kim Tae-Hyung , So Kang Pyo , Cui Yan , Yu Woo Jong , Ra Eun Ju , Lee Young Hee
Published: June 2010

We describe the low-temperature thermal exfoliation of graphite oxide to obtain functionalized graphene sheets (FGSs). Graphite oxide, which is highly oxidized graphite produced by a modified Brodie method, is further exfoliated by a simple heat treatment at 270–275 °C under ambient Ar. The FGSs that are generated have fewer defects and less oxygen content than in commercial graphene sheets (GSs) prepared at high temperatures (>900 °C). X-ray photoelectron spectroscopy demonstrates a clear π-plasmon peak in the FGSs of the type that is seen in precursor graphite, but not in commercial GSs. Thus, our FGSs exhibit high 2D crystallinity and minimal defects.
Light extinction by pores in AlON ceramics: the transmission properties
Authors: Wang Yuezhong , Lu Tiecheng , Gong Li , Qi Jianqi , Wen Jinsong , Yu Jian , Pan Lei , Yu Yin , Wei Nian
Published: June 2010

The transmission properties of aluminium oxynitride (AlON) ceramics were studied. AlON samples with different transmittances were prepared. SEM detected two types of pores with a different range of diameters in the samples; the porosity was obtained by counting the number of pores in a certain area. Mie theory was applied to illuminate the effects of pores on the transmittances. The calculated transmittances were compared with the experiments. The existence of pores with sizes in the 1.1–1.6 µm range and porosities above 10−4 accounted for the degradation of the transmittance spectra at 2.5 µm. Discrepancies of the spectra between the samples were caused mainly by different densities of the A-type pores with sizes above 1 µm. The concepts of critical size and critical concentration were proposed and were quantitatively characterized by critical curves, which divided the regions of translucency and transparency into three parts: R1, R2 and R3 depending on porosity. New approaches on how to control the pore sizes and porosities quantitatively for transparent ceramics design were presented.
Diffusion d’une onde par un coin
Authors: Gérard Patrick , Lebeau Gilles
Published: June 2010

We study the Dirichlet problem for a wave outside a corner with general analytic boundary. In particular, we give the asymptotic expansion of the singularity on the diffracted cone.
Ends of hyperbolic 3-manifolds
Authors: Canary Richard D.
Published: June 2010

Let

N
=

H

3

/

Γ

N = {{\mathbf {H}}^3}/\Gamma

be a hyperbolic

3
3

-manifold which is homeomorphic to the interior of a compact

3
3

-manifold. We prove that

N
N

is geometrically tame. As a consequence, we prove that

Γ
\Gamma

’s limit set

L
Γ

{L_\Gamma }

is either the entire sphere at infinity or has measure zero. We also prove that

N
N

’s geodesic flow is ergodic if and only if

L
Γ

{L_\Gamma }

is the entire sphere at infinity.
Mirror symmetry and rational curves on quintic threefolds: a guide for mathematicians
Authors: Morrison David R.
Published: June 2010

We give a mathematical account of a recent string theory calculation which predicts the number of rational curves on the generic quintic threefold. Our account involves the interpretation of Yukawa couplings in terms of variations of Hodge structure, a new

q
q

-expansion principle for functions on the moduli space of Calabi-Yau manifolds, and the “mirror symmetry” phenomenon recently observed by string theorists.
𝐿²-cohomology, Nash blowup and semismall resolutions
Authors: Youssin Boris
Published: June 2010

We study the structure of

L
2

{L^2}

-forms on singular complex projective varieties with respect to Fubini-Studi metric using resolution of singularities. We show that a semismall resolution of

X
X

has to be small if it can be mapped onto the Nash blowup of

X
X

.
A kinetic formulation of multidimensional scalar conservation laws and related equations
Authors: Lions P.-L. , Perthame B. , Tadmor E.
Published: June 2010

We present a new formulation of multidimensional scalar conservation laws, which includes both the equation and the entropy criterion. This formulation is a kinetic one involving an additional variable called velocity by analogy. We also give some applications of this formulation to new compactness and regularity results for entropy solutions based upon the velocity-averaging lemmas. Finally, we show that this kinetic formulation is in fact valid and meaningful for more general classes of equations like equations involving nonlinear second-order terms.
The inverse eigenvalue problem for real symmetric Toeplitz matrices
Authors: Landau H. J.
Published: June 2010

We show that every set of

n
n

real numbers is the set of eigenvalues of an

n
×
n

n \times n

real symmetric Toeplitz matrix; the matrix has a certain additional regularity. The argument—based on the topological degree—is nonconstructive.
Rigidity of holomorphic mappings and a new Schwarz lemma at the boundary
Authors: Burns Daniel M. , Krantz Steven G.
Published: June 2010

A rigidity theorem for holomorphic mappings, in the nature of the uniqueness statement of the classical one-variable Schwarz lemma, is proved at the boundary of a strongly pseudoconvex domain. The result reduces to an interesting, and apparently new, result even in one complex dimension. The theorem has a variety of geometric and analytic interpretations.
Heights of projective varieties and positive Green forms
Authors: Bost J.-B. , Gillet H. , Soulé C.
Published: June 2010

Using arithmetic intersection theory, a theory of heights for projective varieties over rings of algebraic integers is developed. These heights are generalizations of those considered by Weil, Schmidt, Nesterenko, Philippon, and Faltings. Several of their properties are proved, including lower bounds and an arithmetic Bézout theorem for the height of the intersection of two projective varieties. New estimates for the size of (generalized) resultants are derived. Among the analytic tools used in the paper are “Green forms” for analytic subvarieties, and the existence of positive Green forms is discussed.
On the probability that a random ±1-matrix is singular
Authors: Kahn Jeff , Komlós János , Szemerédi Endre
Published: June 2010

We report some progress on the old problem of estimating the probability,

P
n

{P_n}

, that a random

n
×
n
±
1

n \times n \pm 1

-matrix is singular: Theorem. There is a positive constant

ε
\varepsilon

for which

P
n

>

(
1
−
ε

)
n

{P_n} > {(1 - \varepsilon )^n}

. This is a considerable improvement on the best previous bound,

P
n

=
O
(
1

/

n

)

{P_n} = O(1/\sqrt n )

, given by Komlós in 1977, but still falls short of the often-conjectured asymptotical formula

P
n

=
(
1
+
o
(
1
)
)

n
2

2

1
−
n

{P_n} = (1 + o(1)){n^2}{2^{1 - n}}

. The proof combines ideas from combinatorial number theory, Fourier analysis and combinatorics, and some probabilistic constructions. A key ingredient, based on a Fourier-analytic idea of Halász, is an inequality (Theorem 2) relating the probability that

a
_

∈

R

n

\underline a \in {{\mathbf {R}}^n}

is orthogonal to a random

ε
_

∈

{
±
1

}
n

\underline \varepsilon \in {\{ \pm 1\} ^n}

to the corresponding probability when

ε
_

\underline \varepsilon

is random from

{
−
1
,
0
,
1

}
n

{\{ - 1,0,1\} ^n}

with

P
r
(

ε
i

=
−
1
)
=
P
r
(

ε
i

=
1
)
=
p

Pr({\varepsilon _i} = - 1) = Pr({\varepsilon _i} = 1) = p

and

ε
i

{\varepsilon _i}

’s chosen independently.
On the locus of Hodge classes
Authors: Cattani Eduardo , Deligne Pierre , Kaplan Aroldo
Published: June 2010

Let

S
S

be a nonsingular complex algebraic variety and

V

\mathcal {V}

a polarized variation of Hodge structure of weight

2
p

2p

with polarization form

Q
Q

. Given an integer

K
K

, let

S

(
K
)

{S^{(K)}}

be the space of pairs

(
s
,
u
)

(s,u)

with

s
∈
S

s \in S

,

u
∈

V

s

u \in {\mathcal {V}_s}

integral of type

(
p
,
p
)

(p,p)

, and

Q
(
u
,
u
)
≤
K

Q(u,u) \leq K

. We show in Theorem 1.1 that

S

(
K
)

{S^{(K)}}

is an algebraic variety, finite over

S
S

. When

V

\mathcal {V}

is the local system

H

2
p

(

X
s

,

Z

)

{H^{2p}}({X_s},\mathbb {Z})

/torsion associated with a family of nonsingular projective varieties parametrized by

S
S

, the result implies that the locus where a given integral class of type

(
p
,
p
)

(p,p)

remains of type

(
p
,
p
)

(p,p)

is algebraic.
Flat vector bundles, direct images and higher real analytic torsion
Authors: Bismut Jean-Michel , Lott John
Published: June 2010

We prove a Riemann-Roch-Grothendieck-type theorem concerning the direct image of a flat vector bundle under a submersion of smooth manifolds. We refine this theorem to the level of differential forms. We construct associated secondary invariants, the analytic torsion forms, which coincide in degree 0 with the Ray-Singer real analytic torsion. Résumé. On démontre un analogue du théorème de Riemann-Roch-Grothendieck pour l’image directe d’un fibré plat par une submersion. On raffine ce théorème au niveau des formes différentielles. On construit des invariants secondaires, les formes de torsion analytique, qui coïncident, en degré 0, avec la torsion de Ray-Singer.
The Willmore functional on Lagrangian tori: its relation to area and existence of smooth minimizers
Authors: Minicozzi William P.
Published: June 2010

In this paper we prove an existence and regularity theorem for lagrangian tori minimizing the Willmore functional in Euclidean four-space,

R

4

{{\mathbf {R}}^4}

, with the standard metric and symplectic structure. Technical difficulties arise because the Euler-Lagrange equation for this problem is a sixth-order nonlinear partial differential equation. This research was motivated by a study of the seemingly unrelated Plateau problem for lagrangian tori, and in this paper we illustrate this connection.
WASP Family Proteins: Their Evolution and Its Physiological Implications
Authors: Veltman Douwe M. , Insall Robert H.
Published: June 2010

WASP family proteins control actin polymerization by activating the Arp2/3 complex. Several subfamilies exist, but their regulation and physiological roles are not well understood, nor is it even known if all subfamilies have been identified. Our extensive search reveals few novel WASP family proteins. The WASP, WASH, and SCAR/WAVE subfamilies are evolutionarily ancient, with WASH the most universally present, whereas WHAMM/JMY first appears in invertebrates. An unusual Dictyostelium WASP homologue that has lost the WH1 domain has retained its function in clathrin-mediated endocytosis, demonstrating that WASPs can function with a remarkably diverse domain topology. The WASH and SCAR/WAVE regulatory complexes are much more rigidly maintained; their domain topology is highly conserved, and all subunits are present or lost together, showing that the complexes are ancient and functionally interdependent. Finally, each subfamily has a distinctive C motif, indicating that this motif plays a specific role in each subfamily's function, unlike the generic V and A motifs. Our analysis identifies which features are universally conserved, and thus essential, and which are branch-specific modifications. It also shows the WASP family is more widespread and diverse than currently appreciated and unexpectedly biases the physiological role of the Arp2/3 complex toward vesicle traffic.
DnaK and GroEL are induced in response to antibiotic and heat shock in Acinetobacter baumannii
Authors: Cardoso Karen , Gandra Rinaldo Ferreira , Wisniewski Edirlene Sara , Osaku Clarice Aoki , Kadowaki Marina Kimiko , Felipach-Neto Vicente , Haus Leandro Fávero Aby-Ázar , Simão Rita de Cássia Garcia
Published: June 2010

We studied the expression of DnaK and GroEL in Acinetobacter baumannii cells (strains ATCC 19606 and RS4) under stress caused by heat shock or antibiotics. A Western blot assay showed that DnaK and GroEL levels increased transiently more than 2-fold after exposure of bacterial cells to heat shock for 20 min at 50 °C. Heat induction of DnaK and GroEL was blocked completely when an inhibitor of transcription, rifampicin, was added 1 min before a temperature upshift to 50 °C, suggesting that the induction of these chaperones depends on transcription. A. baumannii cells pretreated at 45 °C for 30 min were better able to survive at 50 °C for 60 min than cells pretreated at 37 °C, indicating that A. baumannii is able to acquire thermotolerance. DnaK and GroEL were successfully induced in cells pre-incubated with a subinhibitory concentration of streptomycin. Moreover, bacterial cells pretreated for 30 min at 45 °C were better able to survive streptomycin exposure than cells pretreated at physiological temperatures. DnaK expression was upregulated in a multidrug-resistant strain of A. baumannii (RS4) in the presence of different antimicrobials (ampicillin+sulbactam, cefepime, meropenem and sulphamethoxazole+trimethoprim). This study is to the best of our knowledge the first to show that A. baumannii DnaK and GroEL could play an important role in the stress response induced by antibiotics.
Regulation of Freezing Tolerance and Flowering in Temperate Cereals: The VRN-1 Connection
Authors: Dhillon Taniya , Pearce Stephen P. , Stockinger Eric J. , Distelfeld Assaf , Li Chengxia , Knox Andrea K. , Vashegyi Ildikó , VÁgújfalvi Attila , Galiba Gabor , Dubcovsky Jorge
Published: June 2010

In winter wheat (Triticum spp.) and barley (Hordeum vulgare) varieties, long exposures to nonfreezing cold temperatures accelerate flowering time (vernalization) and improve freezing tolerance (cold acclimation). However, when plants initiate their reproductive development, freezing tolerance decreases, suggesting a connection between the two processes. To better understand this connection, we used two diploid wheat (Triticum monococcum) mutants, maintained vegetative phase (mvp), that carry deletions encompassing VRN-1, the major vernalization gene in temperate cereals. Homozygous mvp/mvp plants never flower, whereas plants carrying at least one functional VRN-1 copy (Mvp/−) exhibit normal flowering and high transcript levels of VRN-1 under long days. The Mvp/− plants showed reduced freezing tolerance and reduced transcript levels of several cold-induced C-REPEAT BINDING FACTOR transcription factors and COLD REGULATED genes (COR) relative to the mvp/mvp plants. Diploid wheat accessions with mutations in the VRN-1 promoter, resulting in high transcript levels under both long and short days, showed a significant down-regulation of COR14b under long days but not under short days. Taken together, these studies suggest that VRN-1 is required for the initiation of the regulatory cascade that down-regulates the cold acclimation pathway but that additional genes regulated by long days are required for the down-regulation of the COR genes. In addition, our results show that allelic variation in VRN-1 is sufficient to determine differences in freezing tolerance, suggesting that quantitative trait loci for freezing tolerance previously mapped on this chromosome region are likely a pleiotropic effect of VRN-1 rather than the effect of a separate closely linked locus (FROST RESISTANCE-1), as proposed in early freezing tolerance studies.
Linking prey composition of haddock Melanogrammus aeglefinus to benthic prey availability in three different areas of the northern North Sea
Authors: Schückel S. , Ehrich S. , Kröncke I. , Reiss H.
Published: June 2010

The feeding strategy and prey selection of haddock Melanogrammus aeglefinus related to the benthic infauna in the field were investigated in three different study areas (boxes) in the northern North Sea in 2007. The stomach contents of M. aeglefinus were dominated by invertebrates in all three boxes, mainly echinoderms and polychaetes, similar to the benthic communities in the field. Prey densities in the field significantly determined prey selection and, thus the feeding strategy of M. aeglefinus appeared highly opportunistic. Other prey characteristics, such as the position in the sediment or its palatability, had no significant effect on the selection process although trends were apparent that tubicolous polychaetes of the family spionids, especially Spiophanes kröyeri and Spiophanes bombyx as well as the tentaculate Phoronis spp., were not consumed and potentially avoided due to their ability to withdraw below the feeding depths or due to chemical deterrents. High abundances of echinoderm species with hard calcareous shells in the M. aeglefinus stomachs, such as the ophiurid Ophiocten affinis and the echinoid Echinocyamus pusillus, indicated their use as grinding elements. A gradual shift from benthos to fish feeding with increasing M. aeglefinus size was not found.
Involvement of M2‐polarized macrophages in the ascites from advanced epithelial ovarian carcinoma in tumor progression via Stat3 activation
Authors: Takaishi Kiyomi , Komohara Yoshihiro , Tashiro Hironori , Ohtake Hideyuki , Nakagawa Takenobu , Katabuchi Hidetaka , Takeya Motohiro
Published: June 2010

Ascites macrophages in advanced epithelial ovarian cancer (AdEOC) are involved in cancer metastasis and progression by modifying the tumor microenvironment. However, the precise mechanisms of cell‐to‐cell interaction between macrophages and tumor cells are still unclear. This study focused on the activation of signal transducer and activator of transcription 3 (Stat3) which is a critical signal transduction molecule at a point of convergence for numerous oncogenic signaling pathways as well as controlling the M2‐poralization of macrophages. AdEOC ascites, in which high concentration of interleukin (IL)‐6, IL‐10, growth‐related oncogene‐alpha and vascular endothelial growth factor were detected, stimulated the proliferation of SKOV3 cells, a human ovarian cancer cell line. The simultaneous blocking of IL‐6 and IL‐10 by neutralizing antibodies suppressed ascites‐induced tumor cell proliferation. Stat3 activation in SKOV3 cells was induced by co‐culture with macrophages especially with macrophage colony stimulating factor‐primed M2 macrophages but lesser extent with granulocyte‐macrophage colony stimulating factor‐primed immature macrophages. Cyclin‐D1 expression in SKOV3 cells was also significantly induced by co‐culture with macrophages. Blocking of Stat3 in macrophages by small interfering RNA inhibited the production of IL‐6 and IL‐10 by macrophages, and suppressed Stat3 activation and cyclin‐D1 induction in co‐cultured SKOV3 cells. Stat3 activation in SKOV3 cells was abrogated by simultaneous neutralization of IL‐6 and IL‐10. These results indicate that Stat3 activation by IL‐6 and IL‐10 plays an important role in cell‐to‐cell interaction between tumor cells and macrophages in the ascites of AdEOC. (Cancer Sci 2010)
Lipopolysaccharide mobility in leaf tissue of Arabidopsis thaliana
Authors: ZEIDLER DANA , DUBERY IAN A. , SCHMITT‐KOPPLIN PHILLIPPE , VON RAD UTA , DURNER JÖRG
Published: June 2010

Bacterial lipopolysaccharides (LPS) are triggers of defence responses in plants, and induce local as well as systemic acquired resistance. Arabidopsis thaliana plants pretreated with LPS show an increased resistance to the virulent bacterial plant pathogen Pseudomonas syringae pv. tomato DC3000. To investigate the mobilization and transport of LPS in Arabidopsis leaves, fluorescently labelled LPS (Alexa Fluor® 488 conjugate) from Salmonella minnesota was used. Leaves were pressure infiltrated with fluorescein‐labelled LPS and fluorescence microscopy was used to follow the movement and localization of LPS as a function of time. The observation of leaves 1 h after supplementation with fluorescein‐labelled LPS revealed a fluorescent signal in the intercellular space. Capillary zone electrophoresis was used for the detection and analysis of the labelled LPS in directly treated leaves and systemic leaves. In addition, gel electrophoresis was used to confirm LPS mobilization. The results indicated that LPS mobilization/translocation occurs through the xylem from local, treated leaves to systemic, untreated leaves. Consequently, care should be taken when ascribing the observed biochemical responses and induced resistance from LPS perception as being uniquely local or systemic, as these responses might overlap because of the mobility of LPS in the plant vascular system.
Degarelix, a novel GnRH antagonist, causes minimal histamine release compared with cetrorelix, abarelix and ganirelix in an ex vivo model of human skin samples
Authors: Koechling Wolfgang , Hjortkjaer Rolf , Tankó László B.
Published: June 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT?

• Systemic anaphylactic reactions have been described as rare but serious adverse effects of GnRH antagonists.

• The chemical development of degarelix has devoted much attention to the elimination of this risk.

• Side‐by‐side comparison of the histamine releasing capacity of marketed GnRH antagonists in fresh human skin samples has not been reported yet.

WHAT THIS STUDY ADDS

• Our findings indicate considerable differences in the relative propensity of marketed GnRH antagonists to release histamine from cutaneous mast cells.

• These findings are similar but not identical to those obtained with the conventional rat peritoneal mast cell approach.

• With some further refinements the experimental set‐up using human skin samples could become a useful and low‐risk supplement to exploratory safety studies in clinical pharmacology.

AIMS

Early studies on gonadotrophin‐releasing hormone (GnRH) antagonists pointed out histamine‐mediated anaphylactic reactions as a potential adverse effect of these drug candidates. In this study we have compared the histamine‐releasing potential of four approved and marketed antagonists, degarelix, cetrorelix, abarelix and ganirelix in an ex vivo model of human skin samples.

METHODS

Human skin samples were obtained during cosmetic plastic surgery and kept in oxygenated saline solution. The samples were incubated either without or at different concentrations of the antagonists (3, 30 or 300 µg ml−1 for all, except for ganirelix 1, 10 or 100 µg ml−1). The drug‐induced effect was expressed as the increase relative to basal release. The histamine‐releasing capacity of the skin was verified by a universal histamine releaser, compound 40/80.

RESULTS

Degarelix had no significant effect on basal histamine release in the 3 to 300 µg ml−1 concentration range. The effect of ganirelix was moderate causing a nonsignificant increase of 81 ± 27% at the 100 µg ml−1 concentration. At 30 and 300 µg ml−1 concentrations abarelix (143 ± 29% and 362 ± 58%, respectively, P < 0.05) and cetrorelix (228 ± 111% and 279 ± 46%, respectively, P < 0.05) caused significantly increased histamine release.

CONCLUSIONS

In this ex vivo human skin model, degarelix displayed the lowest capacity to release histamine followed by ganirelix, abarelix and cetrorelix. These findings may provide indirect hints as to the relative likelihood of systemic anaphylactic reactions in clinical settings.
Optimizing management of immune tolerance induction in patients with severe haemophilia A and inhibitors: towards evidence‐based approaches
Authors: Coppola Antonio , Di Minno Matteo N. D. , Santagostino Elena
Published: June 2010

Immune tolerance induction (ITI) is the only strategy proven to eradicate persistent inhibitors in severe haemophilia A patients. Thirty years experience has shown high success rates (60–80%) with heterogeneous dose regimens and has led to the identification of clinical features that define the patients’ prognostic profile. Children with recently diagnosed inhibitors are the best candidates for ITI and adequate management may further contribute to improve the short‐ and long‐term ITI outcome. In these patients inhibitor eradication represents a cost‐effective option because it enables the restoration of FVIII prophylaxis and consequently prevents arthropathy development. Adults with long‐standing inhibitors often show bad predictors of ITI outcome, however, ITI may be considered as a suitable and cost‐effective approach in cases with frequent bleeds that are not satisfactorily controlled by by‐passing treatment and/or when orthopaedic surgery is needed. Optimal ITI regimens should be established in these different settings and randomized trials are addressing these issues. This article reviews the available literature evidence and clinical implications with current recommendations on ITI management, and highlights the issues still unsolved.
Anti‐Asthma Simplified Herbal Medicine Intervention‐induced long‐lasting tolerance to allergen exposure in an asthma model is interferon‐γ, but not transforming growth factor‐β dependent
Authors: Srivastava K. , Zhang T. , Yang N. , Sampson H. , Li X. M.
Published: June 2010

Background
Chronic allergic asthma is the result of a T‐helper type 2 (Th2)‐biased immune status. Current asthma therapies control symptoms in some patients, but a long‐lasting therapy has not been established. Anti‐Asthma Simplified Herbal Medicine Intervention (ASHMI™), a Chinese herbal formula improved symptoms and lung function, and reduced Th2 responses in a controlled trial of patients with persistent moderate to severe asthma.

Objective
We evaluated the persistence of ASHMI™ beneficial effects following therapy in a murine model of chronic asthma and the immunological mechanisms underlying such effects.

Methods
BALB/c mice sensitized intraperitoneally with ovalbumin (OVA) received 3 weekly intratracheal OVA challenges to induce airway hyper‐reactivity (AHR) and inflammation (OVA mice). Additionally, OVA mice were treated with ASHMI™ (OVA/ASHMI™) or water (OVA/sham) for 4 weeks, and then challenged immediately and 8 weeks post‐therapy. In other experiments, OVA mice received ASHMI™ treatment with concomitant neutralization of IFN‐γ or TGF‐β. Effects on airway responses, cytokine‐ and OVA‐specific IgE levels were determined 8 weeks post‐therapy.

Results
Before treatment, OVA mice exhibited AHR and pulmonary eosinophilic inflammation following OVA challenge, which was almost completely resolved immediately after completing treatment with ASHMI™ and did not re‐occur following OVA re‐challenge up to 8 weeks post‐therapy. Decreased allergen‐specific IgE and Th2 cytokine levels, and increased IFN‐γ levels also persisted at least 8 weeks post‐therapy. ASHMI™ effects were eliminated by the neutralization of IFN‐γ, but not TGF‐β, during therapy.

Conclusion
ASHMI™ induced long‐lasting post‐therapy tolerance to antigen‐induced inflammation and AHR. IFN‐γ is a critical factor in ASHMI™ effects.

Cite this as: K. Srivastava, T. Zhang, N. Yang, H. Sampson and X. M. Li, Clinical & Experimental Allergy, 2010 (40) 1678–1688.
Biomarkers in bladder cancer
Authors: Proctor Ian , Stoeber Kai , Williams Gareth H
Published: June 2010

Proctor I, Stoeber K & Williams G H (2010) Histopathology 57, 1–13 Biomarkers in bladder cancer

Cancer biomarkers provide an opportunity to diagnose tumours earlier and with greater accuracy. They can also identify those patients most at risk of disease recurrence and predict which tumours will respond to different therapeutic approaches. Such biomarkers will be especially useful in the diagnosis and management of bladder cancer. At present, bladder tumours are diagnosed and followed‐up using a combination of cystoscopic examination, cytology and histology. These are not only expensive, but also highly subjective investigations and reveal little about the underlying molecular characteristics of the tumour. In recent years numerous diagnostic and prognostic biomarkers of bladder cancer have been identified. Two separate approaches to biomarker discovery have been employed. The first is hypothesis‐driven and focuses upon proteins involved in molecular pathways known to be implicated in tumorigenesis. An alternative approach has been to study the global expression of genes (so‐called ‘genomics’) looking for characteristic signatures associated with disease outcomes. In this review we summarize the current state of biomarker development in this field, and examine why so few have made the successful transition into the clinic. Finally, we introduce a novel approach to biomarker development utilizing components of the DNA replication licensing machinery.
A laboratory evaluation of the physical and mechanical properties of selected root canal sealers
Authors: Mokeem‐Saleh A. , Hammad M. , Silikas N. , Qualtrough A. , Watts D. C.
Published: June 2010

Mokeem‐Saleh A, Hammad M, Silikas N, Qualtrough A, Watts DC. A laboratory evaluation of the physical and mechanical properties of selected root canal sealers. International Endodontic Journal, 43, 882–888, 2010.

Aim  To evaluate and compare the porosity, degree of conversion (DC) and hardness of two resin‐based sealers; RealSeal and EndoRez, and a silicon‐based sealer; GuttaFlow to that of a traditional zinc oxide‐based sealer; TubliSeal.

Methodology  For porosity, four samples from each sealer were prepared and scanned using a SkyScan 1072 Micro‐CT. Porosity was then calculated using specialized software. For DC, 10 samples from each sealer were prepared and placed onto a Fourier transform infrared spectroscopy spectrometer. Spectra readings were carried out before and after curing of the sealers, and the DC for each sealer was calculated. For hardness, 10 samples from each sealer were prepared and then tested using a Wallace hardness tester. SPSS software was used for statistical analysis of the data using one‐way anova and independent t‐tests.

Results  TubliSeal had the highest percentage porosity (3.52%), whilst RealSeal had the lowest percentage porosity (0.41%). Statistically significant differences (P = 0.01) in porosity were present between all groups except between RealSeal and EndoRez groups. RealSeal exhibited a significantly higher DC% than EndoRez (P = 0.01), whereas EndoRez had the highest hardness number [28.54 Vickers hardness number (VHN)] whilst TubliSeal showed the lowest (13.57 VHN). Statistically significant differences in hardness were found between all groups (P = 0.01) except between RealSeal and EndoRez groups.

Conclusions  Resin‐based sealers had less porosity, greater hardness and a high DC.
Volatile composition and nutritional quality of the edible mushroom Polyporus tenuiculus grown on different agro‐industrial waste
Authors: Omarini Alejandra , Henning Cynthia , Ringuelet Jorge , Zygadlo Julio A. , Albertó Edgardo
Published: June 2010

The volatile composition and the nutritional value of Polyporus tenuiculus grown on supplemented and nonsupplemented wheat straw and willow sawdust were determined. Thirty‐nine volatile compounds were detected, including acids, esters, alcohols, hydrocarbons, aldehydes and ketones. The main volatile compound in all samples was 1‐octen‐3‐ol, with increasing levels in mushrooms cropped on supplemented substrate. In addition, several precursors of this alcohol were identified in lower percentages. Mushrooms grown on supplemented substrates showed lower fat (5.2–5.7%) and carbohydrate contents (48.2%) and higher protein content (22–22.5%). Fibre and ash contents showed some variations between types of substrates. Compared to other edible fungi, P. tenuiculus high fibre and protein contents point to this species as a healthy nutritional alternative of interest for the food industry. Moreover, the wide spectrum of volatile compounds of P. tenuiculus reveals great potential for biotechnological applications such as the production of “non artificial” mushroom flavour.
Angiogenesis and biomarkers of cardiovascular risk in adults with metabolic syndrome
Authors: Siervo M. , Ruggiero D. , Sorice R. , Nutile T. , Aversano M. , Stephan B. C. M. , Ciullo M.
Published: June 2010

Abstract.  Siervo M, Ruggiero D, Sorice R, Nutile T, Aversano M, Stephan BCM, Ciullo M. (Address: Human Nutrition and Physiology, Department of Neuroscience, University “Federico II”, Faculty of Medicine, Napoli; Institute of Genetics and Biophysics “A. Buzzati‐Traverso”, CNR, Napoli, Italy; and Institute of Public Health, University of Cambridge, UK). Angiogenesis and biomarkers of cardiovascular risk in adults with metabolic syndrome. J Intern Med 2010; 268: 338–347.

Objectives.  Metabolic syndrome (MetSyn) is associated with an increased risk of atherosclerosis and fatal cardiovascular events. Angiogenesis is thought to contribute to this risk as it might be involved in the progression of atherosclerotic plaques. We investigated the levels of circulating biomarkers of angiogenesis and cardiovascular risk in adults with MetSyn and assessed their association with established metabolic risk factors.

Design.  The Genetic Park project is a highly inclusive cross‐sectional survey (about 80% of residents) conducted in three isolated populations in Southern Italy. A total of 1000 men and women (age range: 18–98 years) were included in the analysis. Anthropometric and blood pressure measurements were recorded. Metabolic and cardiovascular biomarkers included glucose, triglycerides, total cholesterol, HDL, vascular endothelial growth factor, placental growth factor (PlGF), soluble fms‐like tyrosine kinase‐1, high‐sensitivity C‐reactive protein, high‐sensitivity troponin T (hs‐TnT) and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP).

Result.  Subjects with MetSyn had higher levels of PlGF and NT‐proBNP after adjustment for age, smoking and body mass index. Circulating levels of PlGF, hs‐TnT and NT‐proBNP were directly related to the number of criteria of MetSyn, and this association interacted with gender. There was a strong correlation between ageing and cardiovascular risk.

Conclusions.  The increase in circulating levels of biomarkers of angiogenesis and cardiac function in subjects with MetSyn mirrors the pathophysiological changes occurring in the cardiovascular system. Over time, these changes might accelerate the formation and progression of atherosclerotic plaques and contribute significantly to cardiovascular morbidity and mortality risk.
Understanding surgery choices for breast cancer: how might the Theory of Planned Behaviour and the Common Sense Model contribute to decision support interventions?
Authors: Sivell Stephanie , Edwards Adrian , Elwyn Glyn , Manstead Antony S. R.
Published: June 2010

Objective  To describe the evidence about factors influencing breast cancer patients’ surgery choices and the implications for designing decision support in reference to an extended Theory of Planned Behaviour (TPB) and the Common Sense Model of Illness Representations (CSM).

Background  A wide range of factors are known to influence the surgery choices of women diagnosed with early breast cancer facing the choice of mastectomy or breast conservation surgery with radiotherapy. However, research does not always reflect the complexities of decision making and is often atheoretical. A theoretical approach, as provided by the CSM and the TPB, could help to identify and tailor support by focusing on patients’ representations of their breast cancer and predicting surgery choices.

Design  Literature search and narrative synthesis of data.

Synthesis  Twenty‐six studies reported women’s surgery choices to be influenced by perceived clinical outcomes of surgery, appearance and body image, treatment concerns, involvement in decision making and preferences of clinicians. These factors can be mapped onto the key constructs of both the TPB and CSM and used to inform the design and development of decision support interventions to ensure accurate information is provided in areas most important to patients.

Conclusions  The TPB and CSM have the potential to inform the design of decision support for breast cancer patients, with accurate and clear information that avoids leading patients to make decisions they may come to regret. Further research is needed examining how the components of the extended TPB and CSM account for patients’ surgery choices.
Confirmatory factor analysis and recommendations for improvement of the Autonomy‐Preference‐Index (API)
Authors: Simon Daniela , Kriston Levente , Loh Andreas , Spies Claudia , Scheibler Fueloep , Wills Celia , Härter Martin
Published: June 2010

Objective  Validation of the German version of the Autonomy‐Preference‐Index (API), a measure of patients’ preferences for decision making and information seeking.

Methods  Stepwise confirmatory factor analysis was conducted on a sample of patients (n = 1592) treated in primary care for depression (n = 186), surgical and internal medicine inpatients (n = 811) and patients with minor trauma treated in an emergency department (n = 595). An initial test of the model was done on calculation and validation halves of the sample. Both local and global indexes‐of‐fit suggested modifications to the scale. The scale was modified and re‐tested in the calculation sample and confirmed in the validation sample. Subgroup analyses for age, gender and type of treatment setting were also performed.

Results  The confirmatory analysis led to a modified version of the API with better local and global indexes‐of‐fit for samples of German‐speaking patients. Two items of the sub‐scale, ‘preference for decision‐making’, and one item of the sub‐scale, ‘preference for information seeking’, showed very low reliability scores and were deleted. Thus, several global indexes‐of‐fit clearly improved significantly. The modified scale was confirmed on the validation sample with acceptable to good indices of fit. Results of subgroup analyses indicated that no adaptations were necessary.

Discussion and conclusions  This first confirmatory analysis for a German‐speaking population showed that the API was improved by the removal of several items. There were theoretically plausible explanations for this improvement suggesting that the modifications might also be appropriate in English and other language versions.
The PRIME project: developing a patient evidence‐base
Authors: Staniszewska Sophie , Crowe Sally , Badenoch Douglas , Edwards Carol , Savage Jan , Norman Will
Published: June 2010

Background  The concept of evidence has become firmly rooted in health care, with most importance placed on the outcome of research in clinical and economic spheres. Much less emphasis is placed on the patient’s contribution to evidence which remains relatively vague, of low status and often difficult to integrate with other forms of knowledge.

Aim  This article proposes a concept of patient‐based evidence, to complement clinical and economic forms of evidence, and demonstrates one way in which it has been operationalized. The PRIME project developed a patient evidence‐base to capture the lived experience of individuals with myalgic encephalitis (ME) or chronic fatigue syndrome (CFS).

Design  Interviews were performed with 40 individuals with ME/CFS who varied in a range of demographic characteristics, including age, gender, and how severely affected individuals were.

Results  PRIME has developed a patient evidence‐base which has an extensive array of experiences data to provide researchers, clinicians and others with an in‐depth insight into the lived experience of ME/CFS that can be used and analysed. Data are grouped into a wide range of themes, which can be downloaded and used in a variety of ways as a source of evidence to enable understanding of the lived experience of ME/CFS and so contribute to the development of a more patient‐focused research agenda in ME/CFS.

Conclusions  While patient‐based evidence used in the PRIME Project provides a useful start, further work is required to develop this area conceptually and methodologically, particularly in relation to how patient‐based evidence can be considered alongside clinical and economic evidence.