bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoactivation mechanism of PAmCherry based on crystal structures of the protein in the dark and fluorescent states
Authors: Subach Fedor V. , Malashkevich Vladimir N. , Zencheck Wendy D. , Xiao Hui , Filonov Grigory S. , Almo Steven C. , Verkhusha Vladislav V.
Published: November 2009

Photoactivatable fluorescent proteins (PAFPs) are required for super-resolution imaging of live cells. Recently, the first red PAFP, PAmCherry1, was reported, which complements the photo-activatable GFP by providing a red super-resolution color. PAmCherry1 is originally “dark” but exhibits red fluorescence after UV-violet light irradiation. To define the structural basis of PAmCherry1 photoactivation, we determined its crystal structure in the dark and red fluorescent states at 1.50 Å and 1.65 Å, respectively. The non-coplanar structure of the chromophore in the dark PAmChery1 suggests the presence of an N-acylimine functionality and a single non-oxidized C
α
-C
β
bond in the Tyr-67 side chain in the cyclized Met-66-Tyr-67-Gly-68 tripeptide. MS data of the chromophore-bearing peptide indicates the loss of 20 Da upon maturation, whereas tandem MS reveals the C
α
–N bond in Met-66 is oxidized. These data indicate that PAmCherry1 in the dark state possesses the chromophore
N
-[(E)-(5-hydroxy-1
H
-imidazol-2-yl)methylidene]acetamide, which, to our knowledge, has not been previously observed in PAFPs. The photoactivated PAmCherry1 exhibits a non-coplanar anionic DsRed-like chromophore but in the
trans
configuration. Based on the crystallographic analysis, MS data, and biochemical analysis of the PAmCherry1 mutants, we propose the detailed photoactivation mechanism. In this mechanism, the excited-state PAmCherry1 chromophore acts as the oxidant to release CO
2
molecule from Glu-215 via a Koble-like radical reaction. The Glu-215 decarboxylation directs the carbanion formation resulting in the oxidation of the Tyr-67 C
α
-C
β
bond. The double bond extends the π-conjugation between the phenolic ring of Tyr-67, the imidazolone, and the N-acylimine, resulting in the red fluorescent chromophore.
Acidianus filamentous virus 1 coat proteins display a helical fold spanning the filamentous archaeal viruses lineage
Authors: Goulet Adeline , Blangy Stéphanie , Redder Peter , Prangishvili David , Felisberto-Rodrigues Catarina , Forterre Patrick , Campanacci Valérie , Cambillau Christian
Published: November 2009

Acidianusfilamentous virus 1 (AFV1), a member of theLipothrixviridaefamily, infects the hyperthermophilic, acidophilic crenarchaeaonAcidianus hospitalis.The virion, covered with a lipidic outer shell, is 9,100-Å long and contains a 20.8-kb linear dsDNA genome. We have identified the two major coat proteins of the virion (MCPs; 132 and 140 amino acids). They bind DNA and form filaments when incubated with linear dsDNA. A C-terminal domain is identified in their crystal structure with a four-helix-bundle fold. In the topological model of the virion filament core, the genomic dsDNA superhelix wraps around the AFV1–132 basic protein, and the AFV1–140 basic N terminus binds genomic DNA, while its lipophilic C-terminal domain is imbedded in the lipidic outer shell. The four-helix bundle fold of the MCPs from AFV1 is identical to that of the coat protein (CP) ofSulfolobus islandicusrod-shaped virus (SIRV), a member of theRudiviridaefamily. Despite low sequence identity between these proteins, their high degree of structural similarity suggests that they could have derived from a common ancestor and could thus define an yet undescribed viral lineage.
Theta–gamma coupling increases during the learning of item–context associations
Authors: Tort Adriano B. L. , Komorowski Robert W. , Manns Joseph R. , Kopell Nancy J. , Eichenbaum Howard
Published: November 2009

Phase-amplitude cross-frequency coupling (CFC) between theta (4–12 Hz) and gamma (30–100 Hz) oscillations occurs frequently in the hippocampus. However, it still remains unclear whether theta–gamma coupling has any functional significance. To address this issue, we studied CFC in local field potential oscillations recorded from the CA3 region of the dorsal hippocampus of rats as they learned to associate items with their spatial context. During the course of learning, the amplitude of the low gamma subband (30–60 Hz) became more strongly modulated by theta phase in CA3, and higher levels of theta–gamma modulation were maintained throughout overtraining sessions. Furthermore, the strength of theta–gamma coupling was directly correlated with the increase in performance accuracy during learning sessions. These findings suggest a role for hippocampal theta–gamma coupling in memory recall.
Synergy between bacterial infection and genetic predisposition in intestinal dysplasia
Authors: Apidianakis Yiorgos , Pitsouli Chrysoula , Perrimon Norbert , Rahme Laurence
Published: November 2009

Accumulating evidence suggests that hyperproliferating intestinal stem cells (SCs) and progenitors drive cancer initiation, maintenance, and metastasis. In addition, chronic inflammation and infection have been increasingly recognized for their roles in cancer. Nevertheless, the mechanisms by which bacterial infections can initiate SC-mediated tumorigenesis remain elusive. Using a
Drosophila
model of gut pathogenesis, we show that intestinal infection with
Pseudomonas aeruginosa
, a human opportunistic bacterial pathogen, activates the c-Jun N-terminal kinase (JNK) pathway, a hallmark of the host stress response. This, in turn, causes apoptosis of enterocytes, the largest class of differentiated intestinal cells, and promotes a dramatic proliferation of SCs and progenitors that serves as a homeostatic compensatory mechanism to replenish the apoptotic enterocytes. However, we find that this homeostatic mechanism can lead to massive over-proliferation of intestinal cells when infection occurs in animals with a latent oncogenic form of the Ras1 oncogene. The affected intestines develop excess layers of cells with altered apicobasal polarity reminiscent of dysplasia, suggesting that infection can directly synergize with the genetic background in predisposed individuals to initiate SC-mediated tumorigenesis. Our results provide a framework for the study of intestinal bacterial infections and their effects on undifferentiated and mature enteric epithelial cells in the initial stages of intestinal cancer. Assessment of progenitor cell responses to pathogenic intestinal bacteria could provide a measure of predisposition for apoptotic enterocyte-assisted intestinal dysplasias in humans.
Metonymy-induced polysemy and the role of suffixation in its resolution in some Slavic languages
Authors: Brdar Mario
Published: November 2009

The central concern of the present paper are metonymy avoidance strategies as a limiting case of polysemy resolution. Specifically, I look into the role of suffixation in the resolution of metonymy-induced polysemy in a number of languages (Germanic, Romance, Slavic and Hungarian) in two frames, animals and their meat, and trees and woods. The particular mix of strategies a language makes use of is of course dependent on its structural makeup. It is established that Slavic languages do not really have many choices apart from suffixation in the resolution of metonymy-induced polysemy. The analysis of patterns of suffixation found in six Slavic languages reveals that unlike compounding, which as good as removes any ambiguity in spite of its underspecificity, suffixation as a polysemy-resolving strategy is even more underspecified, and as an interesting twist, prone to contract additional polysemy or just relegate it to another level.
Symbol and Symptom
Authors: Wilcox Sherman
Published: November 2009

This study examines the developmental routes by which gesture is codified into a linguistic system in the context of the natural signed languages of the deaf. I suggest that gestures follow two routes as they codify, and thus that signed languages provide evidence of how material which begins its developmental life external to the conventional linguistic system, as spontaneous or conventional gestures, is codified as language. The Italian Sign Language modal form ‘impossible’ is studied in detail, exploring the developmental route that led from Roman gestures, through liturgical gestures as depicted in medieval Italian art, through everyday Italian and Neapolitan gestures to its modal meaning.
The inseparability of lexis and grammar
Authors: Römer Ute
Published: November 2009

This paper focuses on the interface of lexis and grammar and provides corpus evidence for the inseparability of two areas that have traditionally been kept apart, both in language teaching and in linguistic analysis and description. The paper will first give an overview of a number of influential research strands and model-building attempts in this area (Pattern Grammar and Collostructional Analysis, among others) and then explore the use of a selected lexical-grammatical pattern, the introductory it pattern (e.g. it is essential for EFL learners to come to grips with connotations, attested example) in corpora of expert and apprentice academic writing.
Making sense of the city
Authors: Fendley Tim
Published: November 2009

This article reviews the principles behind, and development of, a coordinated wayfi nding system for walking in London. Wayfi nding in cities is fundamentally an issue of urban design and architecture, but for this project the use of information design to respond to people’s needs was at the fore. Where urban design is concerned with the space between the buildings, information design is concerned with the space between the ears.
Design impact on New York City parking signs: Motorists pay $600 million in parking violations
Authors: Akwera Gordon
Published: November 2009

In 2005 there were 9.5 million parking tickets issued in New York City (NYC), accounting for $578.6 million in revenues (NYC DOF, 2006). This article describes efforts by Addison’ Information Design to simplify the city’ parking signage. It is based on a presentation given at IIID Vision Plus 12 in Austria and the International Conference on Applications of Information Design at Mälardalen University in Sweden. Addison’ objective was to come up with exploratory alternatives to the extremely confusing parking signs posted throughout New York City. Addison’ Information Design team spent several days deciphering parking signs in areas that had the most number of confusing signs. The team explored out of the box concepts to come up with prototype signage systems that are more usable. To validate these concepts, the signs were user tested. The findings confirmed that participants found the existing signs confusing and extremely hard to understand, since the signs did not fit their mental models. The exploratory concepts, on the other hand, elicited positive feedback due to their unambiguous use of language, hierarchy of information, and clear delineation of regulations. The findings were presented to the Deputy Commissioner of New York City.
Nitrite protects against morbidity and mortality associated with TNF- or LPS-induced shock in a soluble guanylate cyclase–dependent manner
Authors: Cauwels Anje , Buys Emmanuel S. , Thoonen Robrecht , Geary Lisa , Delanghe Joris , Shiva Sruti , Brouckaert Peter
Published: November 2009

Nitrite (NO2−), previously viewed as a physiologically inert metabolite and biomarker of the endogenous vasodilator NO, was recently identified as an important biological NO reservoir in vasculature and tissues, where it contributes to hypoxic signaling, vasodilation, and cytoprotection after ischemia–reperfusion injury. Reduction of nitrite to NO may occur enzymatically at low pH and oxygen tension by deoxyhemoglobin, deoxymyoglobin, xanthine oxidase, mitochondrial complexes, or NO synthase (NOS). We show that nitrite treatment, in sharp contrast with the worsening effect of NOS inhibition, significantly attenuates hypothermia, mitochondrial damage, oxidative stress and dysfunction, tissue infarction, and mortality in a mouse shock model induced by a lethal tumor necrosis factor challenge. Mechanistically, nitrite-dependent protection was not associated with inhibition of mitochondrial complex I activity, as previously demonstrated for ischemia–reperfusion, but was largely abolished in mice deficient for the soluble guanylate cyclase (sGC) α1 subunit, one of the principal intracellular NO receptors and signal transducers in the cardiovasculature. Nitrite could also provide protection against toxicity induced by Gram-negative lipopolysaccharide, although higher doses were required. In conclusion, we show that nitrite can protect against toxicity in shock via sGC-dependent signaling, which may include hypoxic vasodilation necessary to maintain microcirculation and organ function, and cardioprotection.
David Masopust: Tracking tapirs, T cells, and other David Masopusts
Authors: Maxmen Amy
Published: November 2009

Masopust recognizes the vital role that memory T cells play in defending us against chronic infection. Now, an older generation of immunologists is recognizing him.
Characteristics of the localized modes in 2D phononic crystal with heterostructure point defect
Authors: Zhao Yan-Cheng , Wu Ya-Bin , Yuan Li-Bo
Published: November 2009

A heterostructure point defect is constructed based on replacing one circular scatter cylinder with one square scatter cylinder in two-dimensional square arrays of circular aluminum cylinders embedded in an air host. Its localized mode characteristics have been studied by using the plane-wave expansion method in combination with a supercell technique and the sonic pressure distribution of the localized modes is also calculated. The results indicate that the localized modes of the heterostructure point defect appear in the gap. The position and number of the localized modes changes with the rotation and filling fraction of the heterostructure point defect. The pressure distribution of localized modes is decided by its position in the gap. The characteristics controlling the localized modes, based on changing the angle and size of the heterostructure point defect, are expected to have broad applications in directional sonic filters and narrow band sonic waveguides.
Simulation of pure and defective wurtzite-type ZnO
Authors: Maldonado Frank , Stashans Arvids
Published: November 2009

Changes in the structural and electronic properties of zinc oxide (ZnO) due to the O vacancy and F-centre were studied using a semi-empirical quantum-chemical approach based on Hartree–Fock theory. A periodic supercell of 128 atoms was exploited throughout the study. The semi-empirical parameters for the Zn atom are obtained by reproducing the main properties of the ZnO crystal as well as the first three ionization potentials of the Zn atom. The perturbation imposed by the defect leads to atomic relaxation, which is computed and discussed in detail. It is found that electron density redistribution in the vicinity of defects plays an important role in the determination of atomic movements. The introduction of an oxygen vacancy generates a local one-electron energy level placed below the conduction band while the presence of an F-centre produces a local energy level just above the upper valence band of the material. The deep situation of the local energy level corresponding to the F-centre implies that the F-centre cannot serve as a source of unintentional n-type electrical conductivity in ZnO. Changes in the chemical bonding are observed, showing that it becomes slightly more covalent because of oxygen-vacancy-type defects.
Automatic continuity via analytic thinning
Authors: Bingham N. , Ostaszewski A.
Published: November 2009

We use Choquet’s analytic capacitability theorem and the Kestelman-Borwein-Ditor theorem (on the inclusion of null sequences by translation) to derive results on ‘analytic automaticity’ – for instance, a stronger common generalization of the Jones/Kominek theorems that an additive function whose restriction is continuous/bounded on an analytic set

T
T

spanning

R

\mathbb {R}

(e.g., containing a Hamel basis) is continuous on

R

\mathbb {R}

. We obtain results on ‘compact spannability’ – the ability of compact sets to span

R

\mathbb {R}

. From this, we derive Jones’ Theorem from Kominek’s. We cite several applications, including the Uniform Convergence Theorem of regular variation.
Geodesics avoiding subsets in Hadamard manifolds
Authors: Borbély Albert
Published: November 2009

Let

M

n

M^{n}

,

n
≥
3

n\geq 3

, be an

s
s

-hyperbolic (in the sense of Gromov) Hadamard manifold. Let us assume that we are given a family of disjoint convex subsets and a point

o
o

outside these sets. It is shown that if one shrinks these sets by the constant

s
s

, then it is possible to find a complete geodesic through

o
o

that avoids the shrunk sets.
On the positivstellensatz in Weyl’s algebra
Authors: Nahas Joules
Published: November 2009

We use harmonic analysis tools on the Heisenberg group to prove decay and regularity properties for a certain class of partial differential equations. These properties allow us to relax a technical condition for a sum of squares decomposition for the Weyl algebra.
The Lerch zeta and related functions of non-positive integer order
Authors: Cvijović Djurdje
Published: November 2009

It is known that the Lerch (or periodic) zeta function of non-positive integer order,

ℓ

−
n

(
ξ
)

\ell _{-n}(\xi )

,

n
∈

N

0

:=
{
0
,
1
,
2
,
3
,
…
}

n\in \mathbb {N}_{0}:= \{0, 1, 2, 3, \ldots \}

, is a polynomial in

cot
⁡
(
π
ξ
)

\cot (\pi \xi )

of degree

n
+
1

n + 1

. In this paper, a very simple explicit closed-form formula for this polynomial valid for any degree is derived. In addition, novel analogous explicit closed-form formulae for the Legendre chi function, the alternating Lerch zeta function and the alternating Legendre chi function are established. The obtained formulae involve the Carlitz-Scoville tangent and secant numbers of higher order, and the derivative polynomials for tangent and secant are used in their derivation. Several special cases and consequences are pointed out, and some examples are also given.
Dominance of a rational map to the Coble quartic
Authors: Huh Sukmoon
Published: November 2009

We show the dominance of the restriction map from a moduli space of stable sheaves on the projective plane to the Coble sixfold quartic. With the dominance and the interpretation of a stable sheaf on the plane in terms of hyperplane arrangements, we expect these tools to reveal the geometry of the Coble quartic.
On embedding the infinite cyclic coverings of knot complements into three sphere
Authors: Yang Zhiqing
Published: November 2009

We construct a class of knots with the CI

∗

{}^*

property, that is,

π
1

(
M
(
n
)
∣
∂
M
(
n
)
)
≠
{
e
}

\pi _1(M(n)\mid \partial M(n))\neq \{e\}

for some

n
>
0

n>0

. It follows that the infinite cyclic covering of such a knot cannot be embedded in any compact 3-manifold.
The homotopy groups of 𝐿₂𝑇(1)/(𝑣₁) at an odd prime
Authors: Xiugui Liu , Xiangjun Wang , Zihong Yuan
Published: November 2009

In this paper, all spectra are localized at an odd prime. Let

T
(
1
)

T(1)

be the Ravenel spectrum characterized by

B

P

∗

BP_{\ast }

-homology as

B

P

∗

[

t
1

]

BP_{\ast }[t_1]

,

T
(
1
)

/

(

v
1

)

T(1)/(v_1)

be the cofiber of the self-map

v
1

:

Σ

2
p
−
2

T
(
1
)
→
T
(
1
)

v_1: \Sigma ^{2p-2}T(1)\rightarrow T(1)

and

L
2

L_2

denote the Bousfield localization functor with respect to

v
2

−
1

B

P

∗

v_2^{-1}BP_{\ast }

. In this paper, we determine the homotopy groups of

L
2

T
(
1
)

/

(

v
1

)

L_2T(1)/(v_1)

.
Proof of a dynamical Bogomolov conjecture for lines under polynomial actions
Authors: Ghioca Dragos , Tucker Thomas
Published: November 2009

We prove a dynamical version of the Bogomolov conjecture in the special case of lines in

A

m

\mathbb {A}^m

under the action of a map

(

f
1

,
…
,

f
m

)

(f_1,\dots ,f_m)

, where each

f
i

f_i

is a polynomial in

Q

¯

[
X
]

\overline {\mathbb {Q}}[X]

of the same degree.
An asymptotic mean value characterization for 𝑝-harmonic functions
Authors: Manfredi Juan , Parviainen Mikko , Rossi Julio
Published: November 2009

We characterize

p
p

-harmonic functions in terms of an asymptotic mean value property. A

p
p

-harmonic function

u
u

is a viscosity solution to

Δ
p

u
=

div

(

|

∇
u

|

p
−
2

∇
u
)
=
0

\Delta _p u = \mbox {div} ( |\nabla u|^{p-2} \nabla u)=0

with

1
>
p
≤
∞

1> p \leq \infty

in a domain

Ω
\Omega

if and only if the expansion
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="u left-parenthesis x right-parenthesis equals StartFraction alpha Over 2 EndFraction left-brace max Underscript ModifyingAbove upper B Subscript epsilon Baseline left-parenthesis x right-parenthesis With bar Endscripts u plus min Underscript ModifyingAbove upper B Subscript epsilon Baseline left-parenthesis x right-parenthesis With bar Endscripts u right-brace plus StartFraction beta Over StartAbsoluteValue upper B Subscript epsilon Baseline left-parenthesis x right-parenthesis EndAbsoluteValue EndFraction integral Underscript upper B Subscript epsilon Baseline left-parenthesis x right-parenthesis Endscripts u d y plus o left-parenthesis epsilon squared right-parenthesis">

u
(
x
)
=

α
2

{

max

B
ε

(
x
)

¯

u
+

min

B
ε

(
x
)

¯

u
}

+

β

|

B
ε

(
x
)

|

∫

B
ε

(
x
)

u

d
y
+
o
(

ε
2

)

u(x) = \frac {\alpha }{2} \left \{ \max _{\overline {B_\varepsilon (x)}} u + \min _{\overline {B_\varepsilon (x)}} u \right \} + \frac {\beta }{|B_\varepsilon (x)|} \int _{B_\varepsilon (x)} u \,d y + o (\varepsilon ^2)

\]
holds as

ε
→
0

\varepsilon \to 0

for

x
∈
Ω

x\in \Omega

in a weak sense, which we call the viscosity sense. Here the coefficients

α
,
β

\alpha , \beta

are determined by

α
+
β
=
1

\alpha + \beta =1

and

α

/

β
=
(
p
−
2
)

/

(
N
+
2
)

\alpha /\beta = (p-2)/(N+2)

.
MIRAGAA—a methodology for finding coordinated effects of microRNA expression changes and genome aberrations in cancer
Authors: Gaire Raj K. , Bailey James , Bearfoot Jennifer , Campbell Ian G. , Stuckey Peter J. , Haviv Izhak
Published: November 2009

Motivation: Cancer evolves through microevolution where random lesions that provide the biggest advantage to cancer stand out in their frequent occurrence in multiple samples. At the same time, a gene function can be changed by aberration of the corresponding gene or modification of microRNA (miRNA) expression, which attenuates the gene. In a large number of cancer samples, these two mechanisms might be distributed in a coordinated and almost mutually exclusive manner. Understanding this coordination may assist in identifying changes which significantly produce the same functional impact on cancer phenotype, and further identify genes that are universally required for cancer. Present methodologies for finding aberrations usually analyze single datasets, which cannot identify such pairs of coordinating genes and miRNAs.

Results: We have developed MIRAGAA, a statistical approach, to assess the coordinated changes of genome copy numbers and miRNA expression. We have evaluated MIRAGAA on The Cancer Genome Atlas (TCGA) Glioblastoma Multiforme datasets. In these datasets, a number of genome regions coordinating with different miRNAs are identified. Although well known for their biological significance, these genes and miRNAs would be left undetected for being less significant if the two datasets were analyzed individually.

Availability and Implementation: The source code, implemented in R and java, is available from our project web site at http://www.csse.unimelb.edu.au/∼rgaire/MIRAGAA/index.html

Contact:  rgaire@csse.unimelb.edu.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
Scale loss and mortality in angled-and-released eastern sea garfish (Hyporhamphus australis)
Authors: Butcher Paul A. , Broadhurst Matt K. , Hall Karina C. , Cullis Brian R. , Nicoll Robert G.
Published: November 2009

Butcher, P. A., Broadhurst, M. K., Hall, K. C., Cullis, B. R., and Nicoll, R. G. 2010. Scale loss and mortality in angled-and-released eastern sea garfish (Hyporhamphus australis). – ICES Journal of Marine Science, 67: 522–529. The eastern sea garfish (Hyporhamphus australis) is an endemic Australian marine teleost that is angled in large numbers throughout its distribution. Most fish are retained, although some are released, mainly because of size-grading in response to bag limits. Owing to their fragility, there are concerns that few released fish survive. To investigate this assumption, 185 angled and 90 control eastern sea garfish were released in groups of five into holding cages, then monitored for up to 24 h. One control and 93 angled fish died, providing an adjusted angled mortality rate of 49.2%. All fish that ingested their hooks (n=7) subsequently died. Generalized linear mixed models for the remaining mouth-hooked garfish revealed that mortalities were mainly caused by scale loss (p<0.01) and air exposure (p<0.05). Further analyses revealed that scale loss most likely occurred when fish were held with dry bare hands (p<0.05), dropped (p<0.05) and exposed to air (p<0.01), or confined in 20-l buckets (p<0.05) for long periods. Air exposure was not significantly affected by any of the variables. Magnetic resonance imaging of 10 live and 5 dead angled-and-released fish revealed no significant differences in dermal damage, although the fatalities typically had greater abrasions than the survivors. The results demonstrate that the fate of eastern sea garfish can be improved significantly if they are released quickly, without physical contact. This protocol could have similar utility among other released species with deciduous scales.
Clinical Outcomes after Hybrid Coronary Revascularization versus Off-Pump Coronary Artery Bypass
Authors: Vassiliades Thomas A. , Kilgo Patrick D. , Douglas John S. , Babaliaros Vasilis C. , Block Peter C. , Samady Habib , Cates Christopher U. , Rab S. Tanveer , Morris Douglas C
Published: November 2009

Objective

Hybrid coronary revascularization is offered as an alternative strategy for patients with multivessel coronary artery disease (CAD). We present our experience and provide a comparative analysis to off-pump coronary artery bypass grafting (OPCAB).

Methods

Ninety-one patients with multivessel CAD underwent minimally invasive left internal mammary artery to left anterior descending grafting in combination with percutaneous coronary intervention of nonleft anterior descending targets (HYBRID). The primary end point of this study was major adverse cardiac and cerebrovascular events (MACCE), defined as death, stroke, and nonfatal myocardial infarction. MACCE in the HYBRID group were compared with 4175 contemporaneously performed OPCAB operations by logistic (30-day outcomes) and Cox proportional hazards (long-term survival) regression methods. Propensity scoring was used to adjust for potential selection bias.

Results

The 30-day MACCE (death/stroke/nonfatal myocardial infarction) rate was 1.1% for the HYBRID group (0%/0%/1.1%) and 3.0% for the OPCAB group (1.8%/1.1%/0.5%) (odds ratio = 0.47, P = 0.48). Angiographic left internal mammary artery evaluation was obtained in 95.6% of patients (87 of 91) revealing FitzGibbon A patency in 98.0% (96 of 98). The reintervention rate at 1 year for the HYBRID group was 5.5% (5 of 91) and was limited to repeat percutaneous coronary intervention. Three-year survival was statistically similar for the two groups (hazard ratio = 0.44, P = 0.18, see Kaplan-Meier figure).

Conclusions

Hybrid coronary revascularization may be noninferior to OPCAB with respect to early MACCE and 3-year survival in the treatment of multivessel CAD.
Tactile Mapping System
Authors: Oie Tomonori , Suzuki Hisato , Fukuda Toru , Murayama Yoshinobu , Omata Sadao , Kanda Keiichi , Nakayama Yasuhide
Published: November 2009

Objective

We demonstrated that the tactile mapping system (TMS) has a high degree of spatial precision in the distribution mapping of surface elasticity of tissues or organs.

Methods

Samples used were a circumferential section of a small-caliber porcine artery (diameter: ~3 mm) and an elasticity test pattern with a line and space configuration for the distribution mapping of elasticity, prepared by regional micropatterning of a 14-μm thick gelatin hydrogel coating on a polyurethane sheet. Surface topography and elasticity in normal saline were simultaneously investigated by TMS using a probe with a diameter of 5 or 12 μm, a spatial interval of 1 to 5 μm, and an indentation depth of 4 μm.

Results

In the test pattern, a spatial resolution in TMS of <5 μm was acquired under water with a minimal probe diameter and spatial interval of the probe movement. TMS was used for the distribution mapping of surface elasticity in a flat, circumferential section (thickness: ~0.5 mm) of a porcine artery, and the concentric layers of the vascular wall, including the collagen-rich and elastin-rich layers, could be clearly differentiated in terms of surface elasticity at the spatial resolution of <2 μm.

Conclusions

TMS is a simple and inexpensive technique for the distribution mapping of the surface elasticity in vascular tissues at the spatial resolution <2 μm. TMS has the ability to analyze a complex structure of the tissue samples under normal saline.
Robotic Fourth-Arm Enucleation of an Esophageal Leiomyoma and Review of Literature
Authors: Kernstine Kemp H. , Emily S. , Falabella Andres , Ramirez Natalie A. , Anderson Casandra A. , Beblawi Ihab
Published: November 2009

Esophageal leiomyomas are resected in symptomatic and/or malignancy-suspicious cases. Traditionally, they have been removed by laparotomy or thoracotomy and more recently by thoracoscopy and laparoscopy. Mucosal injury is reported as high as 7% of cases but may be higher in unreported general practice. Robotic technology seems to offer advantages. We describe a robotic approach that seems to minimize mobilization of the esophagus, potentially decreasing the likelihood of mucosal injury and postoperative recovery time. We review the literature to evaluate the reports of mucosal injury with the open, minimally invasive, and robotic techniques and describe our own method. To improve efficiency, we use a four-arm technique.
Robotic Right Gastroepiploic Artery Harvesting
Authors: Hirano Yasumitsu , Ishikawa Norihiko , Watanabe Go
Published: November 2009

Objective

Robotic surgery promises to extend the capabilities of the minimally invasive surgeon, and many surgical specialties are applying this new technology. However, there is no report of robotic harvesting of the right gastroepiploic artery (rGEA). We evaluated the possibility of video-endoscopic dissection of the rGEA using the da Vinci surgical system for use in minimally invasive coronary artery bypass surgery.

Methods

The procedure was performed on a porcine rGEA harvesting model using the Tuebingen MIS-Trainer and a pig model. In the pig model, a pneumoperitoneum (maximal pressure, 12 mm Hg) was established after the insertion of a 12-mm trocar (camera) using the open method. The surgical cart was positioned at the head of the pig. A 30-degree three-dimensional camera, using two parallel-arranged three-chip cameras, was inserted and mounted on the middle 12-mm trocar. Under direct visualization, the two lateral surgical arm trocars were then placed at both sides of the camera port. We mounted a permanent cautery hook and Cadiere forceps on the right and left surgical arm, respectively.

Results

We performed harvesting of the rGEA with the permanent cautery hook and Cadiere forceps mounted on the surgical arms. The rGEA were easily visualized and dissection with complete mobilization was achieved without injury in both models. The bleeding from the branch of the rGEA was prevented by use of the permanent cautery hook in the pig model.

Conclusions

We have preliminarily established, in pig, the feasibility of robotic rGEA harvesting without laparotomy, avoiding the risks of abdominal complications and expanding its use for all patients. However, further studies need to be undertaken to prove its practical feasibility in humans using the da Vinci surgical system to make it an effective operation.
Impact of Previous PCI on Hospital Mortality after Off-Pump Coronary Artery Bypass Grafting in Diabetic Patients with Multivessel Disease
Authors: Kinoshita Takeshi , Asai Tohru , Murakami Yoshitaka , Takashima Noriyuki , Hosoba Soh , Nishimura Osamu , Ikegami Hirohisa , Hiramatsu Norihiko , Suzuki Tomoaki , Kambara Atsushi , Matsubayashi Keiji
Published: November 2009

Objective

Because percutaneous coronary intervention (PCI) has been performed excessively, many patients initially managed with PCI are being referred for coronary artery bypass grafting (CABG). The purpose of this study was to assess the impact of previous PCI on surgical mortality after off-pump CABG in diabetic patients with multivessel disease.

Methods

Between January 2002 and April 2008, 595 consecutive patients (99.8% off-pump) had isolated CABG by one single surgeon. Of these, 274 patients with diabetes mellitus and multivessel disease were retrospectively analyzed. Patients with previous PCI (n = 79) were compared with patients with no previous PCI (n = 196), and risk-adjusted impact of previous PCI on surgical mortality after CABG was determined using multivariate and propensity score analyses.

Results

All patients underwent off-pump CABG without conversion to cardiopulmonary bypass during operation. Patients with previous PCI had a significantly higher prevalence of history of myocardial infarction, renal dysfunction, and hemodialysis. Rates of surgical mortality were higher in patients with previous PCI (7.6% versus 1.0%, P = 0.008). After multivariate logistic regression analysis including all potential univariate predictors, previous PCI remained a strong predictor of surgical mortality [odds ratio (OR), 6.9; 95% confidence interval (CI), 1.2 to 42.1; P = 0.035]. After matching and regression adjustment by propensity score, the impact of previous PCI on surgical mortality was similar in direction (matching OR, 6.5; 95% CI, 0.8 to 55.0; P = 0.088; regression adjustment OR, 6.3; 95% CI, 1.2 to 33.6; P = 0.031).

Conclusions

Previous PCI increases the risk of surgical mortality after off-pump CABG in diabetic patients with multivessel disease.
Left Atrial Myxoma
Authors: de Loma Julio Gutiέrrez , Marcos Josέ Francisco Valderrama , Tejedor Josέ María Melero , González Sergio González
Published: November 2009

We report a single case of left atrial giant myxoma excision using the da Vinci S surgical system in a 47-year-old woman. A vacuum extractor device was designed to avoid tumor fragmentation or embolization. The myxoma was entirely removed under aspiration through the extractor device, achieving all the surgical tenets of myxoma excision.
Minimally Invasive Esophagectomy
Authors: Laxa Bernadette U. , Harold Kristi L. , Jaroszewski Dawn E.
Published: November 2009

Objective

Minimally invasive esophagectomy (MIE) can be performed a variety of ways using different techniques for the anastomosis. End-to-end anastomosis (EEA) transoral circular staplers have traditionally been used in gastric bypass surgery with good success. An evaluation of the safety and utility of the EEA transoral circular stapler for esophageal anastomoses in MIE is reviewed.

Methods

A retrospective chart review of all patients who underwent transthoracic MIE with EEA-stapled transoral anastomoses between January 2008 and May 2009 was performed. Patient demographics, indication for esophagectomy, perioperative treatments, intraoperative data, postoperative complications, hospital length of stay, and in-hospital mortality were evaluated.

Results

Twenty-six consecutive patients underwent MIE with EEA circular-stapled transthoracic anastomoses. Twenty-three were male with a mean age of 64 years (32–88). Indications for esophagectomy included esophageal cancer (24), high-grade dysplasia (1), and refractory stricture (1). Fifteen patients (63%) had neoadjuvant chemotherapy and radiation. There were no conversions to open thoracotomy or laparotomy. Mean operative time was 6.0 hours. Eight patients (31%) suffered postoperative complications; including leak from the gastric conduit staple line requiring operative intervention (1), postoperative bleeding requiring multiple transfusions (1), aspiration pneumonia (1), acute respiratory distress syndrome (1), myocardial infarction (1), chylothorax (1), and anastomotic stricture (2). Median hospital length of stay was 9 days (range 6–43). There were no in-hospital mortalities.

Conclusions

In our series, the EEA circular stapler seems technically feasible and relatively safe for an intrathoracic anastomosis in MIE.
Deep phylogeny, ancestral groups and the four ages of life
Authors: Cavalier-Smith Thomas
Published: November 2009

Organismal phylogeny depends on cell division, stasis, mutational divergence, cell mergers (by sex or symbiogenesis), lateral gene transfer and death. The tree of life is a useful metaphor for organismal genealogical history provided we recognize that branches sometimes fuse. Hennigian cladistics emphasizes only lineage splitting, ignoring most other major phylogenetic processes. Though methodologically useful it has been conceptually confusing and harmed taxonomy, especially in mistakenly opposing ancestral (paraphyletic) taxa. The history of life involved about 10 really major innovations in cell structure. In membrane topology, there were five successive kinds of cell: (i) negibacteria, with two bounding membranes, (ii) unibacteria, with one bounding and no internal membranes, (iii) eukaryotes with endomembranes and mitochondria, (iv) plants with chloroplasts and (v) finally, chromists with plastids inside the rough endoplasmic reticulum. Membrane chemistry divides negibacteria into the more advanced Glycobacteria (e.g. Cyanobacteria and Proteobacteria) with outer membrane lipolysaccharide and primitive Eobacteria without lipopolysaccharide (deserving intenser study). It also divides unibacteria into posibacteria, ancestors of eukaryotes, and archaebacteria—the sisters (not ancestors) of eukaryotes and the youngest bacterial phylum. Anaerobic eobacteria, oxygenic cyanobacteria, desiccation-resistant posibacteria and finally neomura (eukaryotes plus archaebacteria) successively transformed Earth. Accidents and organizational constraints are as important as adaptiveness in body plan evolution.
The new biology of ageing
Authors: Partridge Linda
Published: November 2009

Human life expectancy in developed countries has increased steadily for over 150 years, through improvements in public health and lifestyle. More people are hence living long enough to suffer age-related loss of function and disease, and there is a need to improve the health of older people. Ageing is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. This view has been reinforced by the realization that ageing is a disadvantageous trait that evolves as a side effect of mutation accumulation or a benefit to the young, because of the decline in the force of natural selection at later ages. However, important recent discoveries are that mutations in single genes can extend lifespan of laboratory model organisms and that the mechanisms involved are conserved across large evolutionary distances, including to mammals. These mutations keep the animals functional and pathology-free to later ages, and they can protect against specific ageing-related diseases, including neurodegenerative disease and cancer. Preliminary indications suggest that these new findings from the laboratory may well also apply to humans. Translating these discoveries into medical treatments poses new challenges, including changing clinical thinking towards broad-spectrum, preventative medicine and finding novel routes to drug development.
The ecosystem-service chain and the biological diversity crisis
Authors: Mooney Harold A.
Published: November 2009

The losses that are being incurred of the Earth's biological diversity, at all levels, are now staggering. The trend lines for future loss are steeply upward as new adverse drivers of change come into play. The political processes for matching this crisis are now inadequate and the science needs to address this issue are huge and slow to fulfil, even though strong advances have been made. A more integrated approach to evaluating biodiversity in terms that are meaningful to the larger community is needed that can provide understandable metrics of the consequences to society of the losses that are occurring. Greater attention is also needed in forecasting likely diversity-loss scenarios in the near term and strategies for alleviating detrimental consequences. At the international level, the Convention on Biological Diversity must be revisited to make it more powerful to meet the needs that originally motivated its creation. Similarly, at local and regional levels, an ecosystem-service approach to conservation can bring new understanding to the value, and hence the need for protection, of the existing natural capital.
Nature's role in sustaining economic development
Authors: Dasgupta Partha
Published: November 2009

In this paper, I formalize the idea of sustainable development in terms of intergenerational well-being. I then sketch an argument that has recently been put forward formally to demonstrate that intergenerational well-being increases over time if and only if a comprehensive measure of wealth
per capita
increases. The measure of wealth includes not only manufactured capital, knowledge and human capital (education and health), but also natural capital (e.g. ecosystems). I show that a country's comprehensive wealth
per capita
can decline even while gross domestic product (GDP)
per capita
increases and the UN Human Development Index records an improvement. I then use some rough and ready data from the world's poorest countries and regions to show that during the period 1970–2000 wealth
per capita
declined in South Asia and sub-Saharan Africa, even though the Human Development Index (HDI) showed an improvement everywhere and GDP
per capita
increased in all places (except in sub-Saharan Africa, where there was a slight decline). I conclude that, as none of the development indicators currently in use is able to reveal whether development has been, or is expected to be, sustainable, national statistical offices and international organizations should now routinely estimate the (comprehensive) wealth of nations.
Unringing a bell: metazoan phylogenomics and the partition bootstrap
Authors: Siddall Mark E.
Published: November 2009

Several large phylogenomic analyses have recently cast doubt on long‐held beliefs about early metazoan phylogenetic patterns. Those data sets, and the relative bootstrap support for various controversial clades, are reanalysed in the context of parsimony, yielding results that are at considerable odds with the original likelihood or Bayesian findings. Discrepancies are considered in light of the tendency of RAxML to overestimate support values by virtue (sic) of its lazy search algorithm and its autocorrelated pseudoreplication as well as the extraordinary ability for Bayesian analyses to be led astray by missing data. In addition to standard nonparametric bootstrapping as a measure of support, a new strategy involving resampling loci as units, partition bootstrap support, is introduced as a more defensible alternative to resampling nonindependent sites.

 © The Willi Hennig Society 2009.
Multivariate evaluation of pharmacological responses in early clinical trials – a study of rIL‐21 in the treatment of patients with metastatic melanoma
Authors: Rasmussen Morten Arendt , Colding‐Jørgensen Morten , Hansen Lasse Tengbjerg , Bro Rasmus
Published: November 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Analysis of data from clinical trials is often performed using univariate statistics.

• In early phases of clinical drug development, interpretation of rare clinical events can be difficult by univariate methods.

• Principal component analysis has proven successful within related scientific areas such as, for example, genomics and metabonomics, where compression of data and extraction of maximum information are of utmost importance.

WHAT THIS STUDY ADDS

• This study reveals that multivariate chemometric methods coupled with visualization gives a comprehensive overview of early clinical trial data to guide dose and regimen selection and provides additional findings overlooked by traditional univariate methods.

• This method revealed novel pharmacological patterns in the treatment of metastatic melanoma with recombinant interleukin‐21.

AIMS Evaluation of the utility of multivariate data analysis in early clinical drug development.

METHODS A multivariate chemometric approach was developed and applied for evaluating clinical laboratory parameters and biomarkers obtained from two clinical trials investigating recombinant human interleukin‐21 (rIL‐21) in the treatment of patients with malignant melanoma. The Phase I trial was an open‐label, first‐human dose escalation safety and tolerability trial with two separate dosing regimens; six cycles of thrice weekly (3/w) vs. three cycles of daily dosing for 5 days followed by 9 days of rest (5+9) in a total of 29 patients. The Phase II trial investigated efficacy and safety of the ‘5+9’ regimen in 24 patients.

RESULTS From the Phase I trial, separate pharmacological patterns were observed for each regimen, clearly reflecting distinct properties of the two regimens. Relations between individual laboratory parameters were visualized and shown to be responsive to rIL‐21 dosing. In particular, novel systematic pharmacological effects on liver function parameters as well as a bell‐shaped dose–response relationship of the overall pharmacological effects were depicted. In validation of the method, multivariate pharmacological patterns discovered in the Phase I trial could be reproduced by the dataset from the Phase II trial, but not from univariate exploration of the Phase I trial.

CONCLUSIONS The new data analytical approach visualized novel correlations between laboratory parameters that points to specific pharmacological properties. This multivariate chemometric data analysis offers a novel robust, comprehensive and intuitive tool to reveal early pharmacological responses and guide selection of dose regimens.
Ribosome‐associated nucleophosmin 1: increased expression and shuttling activity distinguishes prognostic subtypes in chronic lymphocytic leukaemia
Authors: Rees‐Unwin Karen S. , Faragher Robin , Unwin Richard D. , Adams Julie , Brown Philip J. , Buckle Ann‐Marie , Pettitt Andrew , Hutchinson Claire V. , Johnson Suzanne M. , Pulford Karen , Banham Alison H. , Whetton Anthony D. , Lucas Guy , Mason David Y. , Burthem John
Published: November 2009

Two distinct groups of chronic lymphocytic leukaemia (CLL) are distinguished by the presence or absence of somatic hypermutation of the immunoglobulin heavy‐chain gene. CLL without somatic hypermuataion has an adverse outcome, but the precise biological differences that underlie this more aggressive clinical‐course are unclear. Using a proteomic approach, we found that the two prognostic forms of CLL were consistently distinguished according to their protein expression pattern. The most important difference observed related to the different expression of nucleophosmin 1 between the two forms of CLL. This different expression was not related to apoptosis, proliferation or gene mutation. However, co‐immunoprecipitation experiments identified an association between nucleophosmin 1 and ribosomal proteins. Using immunocytofluorescence, nucleophosmin 1 expression was identified in the nucleoli and nucleoplasm of all cells, but in a proportion of cells, nucleophosmin had been transferred from the nucleoplasm to the cytoplasm. Both the fluorescent intensity, and the frequency of cytoplasmic nucleophosmin 1 expression, was higher in CLL without somatic hypermutation. We propose therefore, that nucleophosmin 1, in association with ribosomal proteins, undergoes nucleo‐cytoplasmic shuttling in CLL. This process is most prominent in un‐mutated CLL and may signify altered protein biosynthesis.