bluuebunny/crossref_metadata_2025 huggingface dataset:
Error and efficiency of simulated tempering simulations
Authors: Rosta Edina , Hummer Gerhard
Published: January 2010

We derive simple analytical expressions for the error and computational efficiency of simulated tempering (ST) simulations. The theory applies to the important case of systems whose dynamics at long times is dominated by the slow interconversion between two metastable states. An extension to the multistate case is described. We show that the relative gain in efficiency of ST simulations over regular molecular dynamics (MD) or Monte Carlo (MC) simulations is given by the ratio of their reactive fluxes, i.e., the number of transitions between the two states summed over all ST temperatures divided by the number of transitions at the single temperature of the MD or MC simulation. This relation for the efficiency is derived for the limit in which changes in the ST temperature are fast compared to the two-state transitions. In this limit, ST is most efficient. Our expression for the maximum efficiency gain of ST simulations is essentially identical to the corresponding expression derived by us for replica exchange MD and MC simulations [E. Rosta and G. Hummer, J. Chem. Phys. 131, 165102 (2009)] on a different route. We find quantitative agreement between predicted and observed efficiency gains in a test against ST and replica exchange MC simulations of a two-dimensional Ising model. Based on the efficiency formula, we provide recommendations for the optimal choice of ST simulation parameters, in particular, the range and number of temperatures, and the frequency of attempted temperature changes.
Potential energy surface and reactive collisions for the Au+H2 system
Authors: Zanchet Alexander , Roncero Octavio , Omar Salama , Paniagua Miguel , Aguado Alfredo
Published: January 2010

A global potential energy surface is obtained for the ground state of the endoergic Au(S2)+H2(X Σ1g+)→AuH(Σ1+)+H(S2) reaction. The global potential is obtained by fitting highly correlated ab initio calculations on the system, using relativistic pseudopotential for the gold atom. Several electronic states are calculated correlating with Au(S2)+H2, Au(D2)+H2, and H2, Au(P2)+H2 asymptotes. These states show several conical intersections and curve crossings along the minimum energy reaction path which are analyzed in detail. One of them gives rise to an insertion well in which there are important contributions from the Au(D2) and Au(P2) states of gold, which is interesting because it is analog to the deep chemisorption well appearing in larger gold clusters. Quantum wave packet and quasiclassical trajectory dynamical calculations performed for the reaction at zero total angular momentum are in good agreement, provided that a Gaussian binning method is used to account for the zero-point energy of products. Finally, integral and differential cross sections are calculated for the reaction with quasiclassical trajectories. Two different reaction mechanisms are found, one direct and the second indirect, in which the Au atom inserts in between the two hydrogen atoms because of the existence of the insertion well discussed above.
Ion acoustic solitary waves and double layers in dense electron-positron-ion magnetoplasma
Authors: Chatterjee Prasanta , Saha Taraknath , Muniandy S. V. , Wong C. S. , Roychoudhury Rajkumar
Published: January 2010

The existence of ion acoustic solitary waves is studied in a magnetized dense electron-positron-ion plasma. The ions are described by the hydrodynamic equations, and the electron and positron are assumed to follow the Thomas–Fermi density distribution. The pseudopotential is derived directly from the basic equations including Poisson’s equation without assuming the quasineutrality condition. The effect of ion temperature on the solitary waves is studied, and the ranges of parameters for which solitary waves and double layers exist are also studied in detail using Sagdeev’s technique.
Three-dimensional vorticity measurements in the wake of a yawed circular cylinder
Authors: Zhou T. , Wang H. , Razali S. F. Mohd. , Zhou Y. , Cheng L.
Published: January 2010

Using a phase-averaged technique, the dependence of the wake vortical structures on cylinder yaw angle α (=0°–45°) was investigated by measuring all three-velocity and vorticity components simultaneously using an eight-hot wire vorticity probe in the intermediate region (x/d=10) of a yawed stationary circular cylinder wake. For all yaw angles, the phase-averaged velocity and vorticity contours display apparent Kármán vortices. It is found that when α≤15°, the maximum coherent concentrations of the three vorticity components do not change with α. However, when α is increased to 45°, the maximum concentrations of the coherent transverse and spanwise vorticity components decrease by about 33% and 50%, respectively, while that of the streamwise vorticity increases by about 70%, suggesting that the strength of the Kármán vortex shed from the yawed cylinder decreases and the three dimensionality of the flow is enhanced. The maximum coherent concentrations of u and v contours decrease by more than 20% while that of w increases by 100%. Correspondingly, the coherent contributions to the velocity variances ⟨u2⟩ and ⟨v2⟩ decrease, while that of ⟨w2⟩ increases. These results may indicate the generation of the secondary axial vortices in yawed cylinder wakes when α is larger than 15°. The incoherent vorticity contours ⟨ωxr2⟩ are stretched along an axis inclining to the x-axis at an angle β in the range of 60°–25° for α=0°–45°. The magnitudes of ⟨ωxr2⟩∗ and ⟨ωyr2⟩∗ through the saddle points are comparable to the maximum concentration of the coherent spanwise vorticity ω̃z∗ at all cylinder yaw angles, supporting the previous speculation that the strength of the riblike structures in the cylinder wake is about the same as that of the spanwise structures, even in the yawed cylinder wakes.
Effects of nonuniversal large scales on conditional structure functions in turbulence
Authors: Blum Daniel B. , Kunwar Surendra B. , Johnson James , Voth Greg A.
Published: January 2010

We report measurements of conditional Eulerian and Lagrangian structure functions in order to assess the effects of nonuniversal properties of the large scales on the small scales in turbulence. We study a 1×1×1.5 m3 flow between oscillating grids which produces Rλ=285 while containing regions of nearly homogeneous and highly inhomogeneous turbulence. Large data sets of three-dimensional tracer particle velocities have been collected using stereoscopic high speed cameras with real-time image compression technology. Eulerian and Lagrangian structure functions are measured in both homogeneous and inhomogeneous regions of the flow. We condition the structure functions on the instantaneous large scale velocity or on the grid phase. At all scales, the structure functions depend strongly on the large scale velocity, but are independent of the grid phase. We see clear signatures of inhomogeneity near the oscillating grids, but even in the homogeneous region in the center we see a surprisingly strong dependence on the large scale velocity that remains at all scales. Previous work has shown that similar correlations extend to very high Reynolds numbers. Comprehensive measurements of these effects in a laboratory flow provide a powerful tool for assessing the effects of shear, inhomogeneity and intermittency of the large scales on the small scales in turbulence.
Neuroprotection by selective allosteric potentiators of the EP2 prostaglandin receptor
Authors: Jiang Jianxiong , Ganesh Thota , Du Yuhong , Thepchatri Pahk , Rojas Asheebo , Lewis Iestyn , Kurtkaya Serdar , Li Lian , Qui Min , Serrano Geidy , Shaw Renee , Sun Aiming , Dingledine Ray
Published: January 2010

Activation of the Gαs-coupled EP2 receptor for prostaglandin E2 (PGE
2
) promotes cell survival in several models of tissue damage. To advance understanding of EP2 functions, we designed experiments to develop allosteric potentiators of this key prostaglandin receptor. Screens of 292,000 compounds identified 93 that at 20 μM (
i
) potentiated the cAMP response to a low concentration of PGE
2
by > 50%; (
ii
) had no effect on EP4 or β2 adrenergic receptors, the cAMP assay itself, or the parent cell line; and (
iii
) increased the potency of PGE
2
on EP2 receptors at least 3-fold. In aqueous solution, the active compounds are largely present as nanoparticles that appear to serve as active reservoirs for bioactive monomer. From 94 compounds synthesized or purchased, based on the modification of one hit compound, the most active increased the potency of PGE
2
on EP2 receptors 4- to 5-fold at 10 to 20 μM and showed substantial neuroprotection in an excitotoxicity model. These small molecules represent previously undescribed allosteric modulators of a PGE
2
receptor. Our results strongly reinforce the notion that activation of EP2 receptors by endogenous PGE
2
released in a cell-injury setting is neuroprotective.
Impact of generalized brain arousal on sexual behavior
Authors: Weil Zachary M. , Zhang Qiuyu , Hornung Allison , Blizard David , Pfaff Donald W.
Published: January 2010

Although there is an extensive amount known about specific sensory and motor functions of the vertebrate brain, less is understood about the regulation of global brain states. We have recently proposed that a function termed generalized arousal (Ag) serves as the most elemental driving force in the nervous system, responsible for the initial activation of all behavioral responses. An animal with increased generalized CNS arousal is characterized by greater motor activity, increased responsivity to sensory stimuli, and greater emotional lability. Implicit in this theory was the prediction that increases in generalized arousal would augment specific motivated behaviors that depend on arousal. Here, we address the idea directly by testing two lines of mice bred for high or low levels of generalized arousal and assessing their responses in tests of specific forms of behavioral arousal, sex and anxiety/exploration. We report that animals selected for differential generalized arousal exhibit marked increases in sensory, motor, and emotional reactivity in our arousal assay. Furthermore, male mice selected for high levels of generalized arousal were excitable and showed more incomplete mounts before the first intromission (IN), but having achieved that IN, they exhibited far fewer IN before ejaculating, as well as ejaculating much sooner after the first IN, thus indicating a high level of sexual arousal. Additionally, high-arousal animals of both sexes exhibited greater levels of anxiety-like behaviors and reduced exploratory behavior in the elevated plus maze and light-dark box tasks. Taken together, these data illustrate the impact of Ag on motivated behaviors.
Pfaffian presentations of elliptic normal curves
Authors: Fisher Tom
Published: January 2010

We investigate certain alternating matrices of linear forms whose Pfaffians generate the homogeneous ideal of an elliptic normal curve, or one of its higher secant varieties.
On asymptotic Teichmüller space
Authors: Fletcher Alastair
Published: January 2010

In this article we prove that for any hyperbolic Riemann surface

M
M

of infinite analytic type, the little Bers space

Q

0

(
M
)

Q_{0}(M)

is isomorphic to

c

0

c_{0}

. As a consequence of this result, if

M
M

is such a Riemann surface, then its asymptotic Teichmüller space

A
T
(
M
)

AT(M)

is bi-Lipschitz equivalent to a bounded open subset of the Banach space

l

∞

/

c

0

l^{\infty }/c_{0}

. Further, if

M
M

and

N
N

are two such Riemann surfaces, their asymptotic Teichmüller spaces,

A
T
(
M
)

AT(M)

and

A
T
(
N
)

AT(N)

, are locally bi-Lipschitz equivalent.
Decomposition numbers for finite Coxeter groups and generalised non-crossing partitions
Authors: Krattenthaler C. , Müller T.
Published: January 2010

Given a finite irreducible Coxeter group

W
W

, a positive integer

d
d

, and types

T
1

,

T
2

,
…
,

T
d

T_1,T_2,\dots ,T_d

(in the sense of the classification of finite Coxeter groups), we compute the number of decompositions

c
=

σ
1

σ
2

⋯

σ
d

c=\sigma _1\sigma _2\cdots \sigma _d

of a Coxeter element

c
c

of

W
W

, such that

σ
i

\sigma _i

is a Coxeter element in a subgroup of type

T
i

T_i

in

W
W

,

i
=
1
,
2
,
…
,
d

i=1,2,\dots ,d

, and such that the factorisation is “minimal” in the sense that the sum of the ranks of the

T
i

T_i

’s,

i
=
1
,
2
,
…
,
d

i=1,2,\dots ,d

, equals the rank of

W
W

. For the exceptional types, these decomposition numbers have been computed by the first author in [“Topics in Discrete Mathematics,” M. Klazar et al. (eds.), Springer–Verlag, Berlin, New York, 2006, pp. 93–126] and [Séminaire Lotharingien Combin. 54 (2006), Article B54l]. The type

A
n

A_n

decomposition numbers have been computed by Goulden and Jackson in [Europ. J. Combin. 13 (1992), 357–365], albeit using a somewhat different language. We explain how to extract the type

B
n

B_n

decomposition numbers from results of Bóna, Bousquet, Labelle and Leroux [Adv. Appl. Math. 24 (2000), 22–56] on map enumeration. Our formula for the type

D
n

D_n

decomposition numbers is new. These results are then used to determine, for a fixed positive integer

l
l

and fixed integers

r
1

≤

r
2

≤
⋯
≤

r
l

r_1\le r_2\le \dots \le r_l

, the number of multi-chains

π
1

≤

π
2

≤
⋯
≤

π
l

\pi _1\le \pi _2\le \dots \le \pi _l

in Armstrong’s generalised non-crossing partitions poset, where the poset rank of

π
i

\pi _i

equals

r
i

r_i

and where the “block structure” of

π
1

\pi _1

is prescribed. We demonstrate that this result implies all known enumerative results on ordinary and generalised non-crossing partitions via appropriate summations. Surprisingly, this result on multi-chain enumeration is new even for the original non-crossing partitions of Kreweras. Moreover, the result allows one to solve the problem of rank-selected chain enumeration in the type

D
n

D_n

generalised non-crossing partitions poset, which, in turn, leads to a proof of Armstrong’s

F
=
M

F=M

Conjecture in type

D
n

D_n

, thus completing a computational proof of the

F
=
M

F=M

Conjecture for all types. It also allows one to address another conjecture of Armstrong on maximal intervals containing a random multi-chain in the generalised non-crossing partitions poset.
Prime numbers in logarithmic intervals
Authors: Bazzanella Danilo , Languasco Alessandro , Zaccagnini Alessandro
Published: January 2010

Let

X
X

be a large parameter. We will first give a new estimate for the integral moments of primes in short intervals of the type

(
p
,
p
+
h
]

(p,p+h]

, where

p
≤
X

p\leq X

is a prime number and

h
=
o
(
X
)

h=o(X)

. Then we will apply this to prove that for every

λ
>
1

/

2

\lambda >1/2

there exists a positive proportion of primes

p
≤
X

p\leq X

such that the interval

(
p
,
p
+
λ
log
⁡
X
]

(p,p+ \lambda \log X]

contains at least a prime number. As a consequence we improve Cheer and Goldston’s result on the size of real numbers

λ
>
1

\lambda >1

with the property that there is a positive proportion of integers

m
≤
X

m\leq X

such that the interval

(
m
,
m
+
λ
log
⁡
X
]

(m,m+ \lambda \log X]

contains no primes. We also prove other results concerning the moments of the gaps between consecutive primes and about the positive proportion of integers

m
≤
X

m\leq X

such that the interval

(
m
,
m
+
λ
log
⁡
X
]

(m,m+ \lambda \log X]

contains at least a prime number. The last applications of these techniques are two theorems (the first one unconditional and the second one in which we assume the validity of the Riemann Hypothesis and of a form of the Montgomery pair correlation conjecture) on the positive proportion of primes

p
≤
X

p\leq X

such that the interval

(
p
,
p
+
λ
log
⁡
X
]

(p,p+ \lambda \log X]

contains no primes.
Actions of semisimple Lie groups preserving a degenerate Riemannian metric
Authors: Bekkara E. , Frances C. , Zeghib A.
Published: January 2010

We prove a rigidity of the lightcone in Minkowski space. It is (essentially) the unique space endowed with a lightlike metric and supporting an isometric nonproper action of a semisimple Lie group.
The spectral sequence of an equivariant chain complex and homology with local coefficients
Authors: Papadima Stefan , Suciu Alexander
Published: January 2010

We study the spectral sequence associated to the filtration by powers of the augmentation ideal on the (twisted) equivariant chain complex of the universal cover of a connected CW-complex

X
X

. In the process, we identify the

d
1

d^1

differential in terms of the coalgebra structure of

H
∗

(
X
,
k
)

H_*(X,\Bbbk )

and the

k

π
1

(
X
)

\Bbbk \pi _1(X)

-module structure on the twisting coefficients. In particular, this recovers in dual form a result of Reznikov on the mod

p
p

cohomology of cyclic

p
p

-covers of aspherical complexes. This approach provides information on the homology of all Galois covers of

X
X

. It also yields computable upper bounds on the ranks of the cohomology groups of

X
X

, with coefficients in a prime-power order, rank one local system. When

X
X

admits a minimal cell decomposition, we relate the linearization of the equivariant cochain complex of the universal abelian cover to the Aomoto complex, arising from the cup-product structure of

H
∗

(
X
,
k
)

H^*(X,\Bbbk )

, thereby generalizing a result of Cohen and Orlik.
Traces of heat operators on Riemannian foliations
Authors: Richardson Ken
Published: January 2010

We consider the basic heat operator on functions on a Riemannian foliation of a compact, Riemannian manifold, and we show that the traceKB(t)K_{B}(t)of this operator has a particular asymptotic expansion ast→0t\to 0. The coefficients oftαt^{\alpha }and oftα(log⁡t)βt^{\alpha }(\log t)^{\beta }in this expansion are obtainable from local transverse geometric invariants - functions computable by analyzing the manifold in an arbitrarily small neighborhood of a leaf closure. Using this expansion, we prove some results about the spectrum of the basic Laplacian, such as the analogue of Weyl’s asymptotic formula. Also, we explicitly calculate the first two nontrivial coefficients of the expansion for special cases such as codimension two foliations and foliations with regular closure.
Fast and accurate long-read alignment with Burrows–Wheeler transform
Authors: Li Heng , Durbin Richard
Published: January 2010

Motivation: Many programs for aligning short sequencing reads to a reference genome have been developed in the last 2 years. Most of them are very efficient for short reads but inefficient or not applicable for reads >200 bp because the algorithms are heavily and specifically tuned for short queries with low sequencing error rate. However, some sequencing platforms already produce longer reads and others are expected to become available soon. For longer reads, hashing-based software such as BLAT and SSAHA2 remain the only choices. Nonetheless, these methods are substantially slower than short-read aligners in terms of aligned bases per unit time.

Results: We designed and implemented a new algorithm, Burrows-Wheeler Aligner's Smith-Waterman Alignment (BWA-SW), to align long sequences up to 1 Mb against a large sequence database (e.g. the human genome) with a few gigabytes of memory. The algorithm is as accurate as SSAHA2, more accurate than BLAT, and is several to tens of times faster than both.

Availability:  http://bio-bwa.sourceforge.net

Contact:  rd@sanger.ac.uk
Systematic Review of the Evidence Base for the Medical Treatment of Paediatric Inflammatory Bowel Disease
Authors: Wilson DC , Thomas AG , Croft NM , Newby E , Akobeng AK , Sawczenko A , Fell JME , Murphy MS , Beattie RM , Sandhu BK , Mitton SG ,   IBD Working Group of the British Society of Paediatric Gastroenterology, Hepatology, and Nutrition
Published: January 2010

Objective:

To systematically review the evidence base for the medical (pharmaceutical and nutritional) treatment of paediatric inflammatory bowel disease.

Methods:

Key clinical questions were formulated regarding different treatment modalities used in the treatment of paediatric (not adult‐onset) IBD, in particular the induction and maintenance of remission in Crohn disease and ulcerative colitis. Electronic searches were performed from January 1966 to December 2006, using the electronic search strategy of the Cochrane IBD group. Details of papers were entered on a dedicated database, reviewed in abstract form, and disseminated in full for appraisal. Clinical guidelines were appraised using the AGREE instrument and all other relevant papers were appraised using Scottish Intercollegiate Guidelines Network methodology, with evidence levels given to all papers.

Results:

A total of 6285 papers were identified, of which 1255 involved children; these were entered on the database. After critical appraisal, only 103 publications met our criteria as evidence on medical treatment of paediatric IBD. We identified 3 clinical guidelines, 1 systematic review, and 16 randomised controlled trials; all were of variable quality, with none getting the highest methodological scores.

Conclusions:

This is the first comprehensive review of the evidence base for the treatment of paediatric IBD, highlighting the paucity of trials of high methodological quality. As a result, the development of clinical guidelines for managing children and young people with IBD must be consensus based, informed by the best‐available evidence from the paediatric literature and high‐quality data from the adult IBD literature, together with the clinical expertise and multidisciplinary experience of paediatric IBD experts.
In vitro synergistic interactions of oleanolic acid in combination with isoniazid, rifampicin or ethambutol against Mycobacterium tuberculosis
Authors: Ge Fa , Zeng Fanli , Liu Siguo , Guo Na , Ye Haiqing , Song Yu , Fan Junwen , Wu Xiuping , Wang Xuelin , Deng Xuming , Jin Qi , Yu Lu
Published: January 2010

Reports have shown that oleanolic acid (OA), a triterpenoid, exists widely in food, medicinal herbs and other plants, and that it has antimycobacterial activity against the Mycobacterium tuberculosis strain H37Rv (ATCC 27294). In this study it was found that OA had antimycobacterial properties against eight clinical isolates of M. tuberculosis and that the MICs of OA against drug-sensitive and drug-resistant isolates were 50–100 and 100–200 μg ml−1, respectively. The combination of OA with isoniazid (INH), rifampicin (RMP) or ethambutol (EMB) showed favourable synergistic antimycobacterial effects against six drug-resistant strains, with fractional inhibitory concentration indices of 0.121–0.347, 0.113–0.168 and 0.093–0.266, respectively. The combination treatments of OA/INH, OA/RMP and OA/EMB displayed either a synergistic interaction or did not show any interaction against two drug-sensitive strains. No antagonism resulting from the OA/INH, OA/RMP or OA/EMB combination was observed for any of the strains tested. OA exhibited a relatively low cytotoxicity in Vero cells. These results indicate that OA may serve as a promising lead compound for future antimycobacterial drug development.
α 1-Acid glycoprotein as a putative biomarkerfor monitoring the development of the type II reactional stage of leprosy
Authors: Gupta Nishma , Shankernarayan Nallakandy P. , Dharmalingam Kuppamuthu
Published: January 2010

Leprosy, a spectral disease manifested on the basis of host immune responses,is complicated by its reactional stages, namely type I reversal reaction (RR)and type II erythema nodosum leprosum (ENL). These reactional stagesare characterized by uncontrolled and aberrant immune responses. Biomarkersfor reactional stages would aid in early diagnosis, efficient treatment, preventionof neurological complications and prediction of predisposition to reactionalstages. In this study, comparative analysis of the serum proteome of leprosypatients by two-dimensional electrophoresis (2DE) followed by massspectrometry showed differential expression of acute-phase proteinα1-acid glycoprotein (AGP; also known as orosomucoid).AGP levels in untreated ENL cases were significantly higher than in lepromatousleprosy (LL; a non-reactional disease stage) (P=0.0126),RR (P=0.0176) and healthy controls (P=0.0030).These data were confirmed using ELISA. The levels of AGP decreased to normallevels after treatment with multidrug therapy and thalidomide (P=0.0167). In a follow-up study, AGP levels, which were highin the untreated ENL stage, decreased significantly at 5 days (P=0.0084) and 21 days (P=0.0027)post-treatment. A stage-dependent increase in AGP in an LL patient who progressedinto the ENL stage was also shown. Glycosylation analysis by 2DE showed differentialexpression of acidic glycoforms of AGP in untreated ENL cases. Changes inAGP concentration and differential expression of isoforms correlated withthe inflammatory condition in ENL and also with the treatment regimen. Thus,initial validation of AGP as an ENL-specific biomarker and treatment indicatorwas shown in this study.
Isolation of Carnobacterium sp. from a human blood culture
Authors: Hoenigl Martin , Grisold Andrea J. , Valentin Thomas , Leitner Eva , Zarfel Gernot , Renner Heiko , Krause Robert
Published: January 2010

Carnobacteriumspecies have been isolated from the environmentand are not regarded as human pathogens, although they are known to causedisease in fish. Only two reports describing isolation ofCarnobacteriumspecies from human pus were found in the literature. We report whatwe believe to be the first isolation ofCarnobacteriumsp. from ahuman blood culture.
Glucose and glucose 6-phosphate as carbon sources in extra- and intracellular growth of enteroinvasive Escherichia coli and Salmonella enterica
Authors: Götz Andreas , Goebel Werner
Published: January 2010

To study the role of carbohydrates, in particular glucose, glucose 6-phosphate and mannose, as carbon substrates for extra- and intracellular replication of facultative intracellular enteric bacteria, mutants of two enteroinvasiveEscherichia coli(EIEC) strains and aSalmonella entericaserovar Typhimurium isolate were constructed that were defective in the uptake of glucose and mannose (ΔptsG,manXYZ), glucose 6-phosphate (ΔuhpT) or all three carbohydrates (ΔptsG,manXYZ,uhpT). The ability of these mutants to grow in RPMI medium containing the respective carbohydrates and in Caco-2 cells was compared with that of the corresponding wild-type strains. In the three strains, deletions ofptsG,manXYZoruhpTresulted in considerably different levels of inhibition of growthin vitroin the presence of glucose, mannose and glucose 6-phosphate, respectively, but hardly reduced their capability for intracellular replication in Caco-2 cells. Even the triple mutants ΔptsG,manXYZ,uhpTof the three enterobacterial strains were still able to replicate in Caco-2 cells, albeit at strain-specific lower rates than the corresponding wild-type strains.
Characterization of the Haemophilus influenzae tehB gene and its role in virulence
Authors: Whitby Paul W. , Seale Thomas W. , Morton Daniel J. , VanWagoner Timothy M. , Stull Terrence L.
Published: January 2010

The Haemophilus influenzae ORF designated HI1275 in the Rd KW20 genomic sequence encodes a putative S-adenosyl methyltransferase with significant similarity to tellurite-resistance determinants (tehB) in other species. While the H. influenzae tehB can complement an Escherichia coli tehB mutation, thus restoring tellurite resistance, its role in H. influenzae is unknown. In a previous study defining the iron and haem modulon of H. influenzae, we showed that transcription of this gene in H. influenzae Rd KW20 increases during growth in iron- and haem-restricted media. Since iron and haem uptake genes, and other known virulence factors, constitute the majority of the iron- and haem-regulated gene set, we postulated that tehB may play a role in nutrient acquisition and/or the virulence of H. influenzae. A tehB mutant was constructed in the H. influenzae type b strain 10810 and was evaluated for growth defects in various supplemented media, as well as for its ability to cause infection in rat models of infection. Deletion of tehB leads to an increase in sensitivity both to tellurite and to the oxidizing agents cumene hydroperoxide, tert-butyl hydroperoxide and hydrogen peroxide. The tehB mutant additionally showed a significantly reduced ability to utilize free haem as well as several haem-containing moieties including haem–human serum albumin, haemoglobin and haemoglobin–haptoglobin. Examination of the regulation kinetics indicated that transcription of tehB was independent of both tellurite exposure and oxidative stress. Paired comparisons of the tehB mutant and the wild-type H. influenzae strain 10810 showed that tehB is required for wild-type levels of infection in rat models of H. influenzae invasive disease. To our knowledge this is the first report of a role for tehB in virulence in any bacterial species. These data demonstrate that H. influenzae tehB plays a role in both resistance to oxidative damage and haem uptake/utilization, protects H. influenzae from tellurite exposure, and is important for virulence of this organism in an animal model of invasive disease.
Inulin and levan synthesis by probiotic Lactobacillus gasseri strains: characterization of three novel fructansucrase enzymes and their fructan products
Authors: Anwar Munir A. , Kralj Slavko , Piqué Anna Villar , Leemhuis Hans , van der Maarel Marc J. E. C. , Dijkhuizen Lubbert
Published: January 2010

Fructansucrase enzymes polymerize the fructose moiety of sucrose into levan or inulin fructans, with β(2-6) and β(2-1) linkages, respectively. Here, we report an evaluation of fructan synthesis in three Lactobacillus gasseri strains, identification of the fructansucrase-encoding genes and characterization of the recombinant proteins and fructan (oligosaccharide) products. High-performance anion-exchange chromatography and nuclear magnetic resonance analysis of the fructo-oligosaccharides (FOS) and polymers produced by the L. gasseri strains and the recombinant enzymes revealed that, in situ, L. gasseri strains DSM 20604 and 20077 synthesize inulin (and oligosaccharides) and levan products, respectively. L. gasseri DSM 20604 is only the second Lactobacillus strain shown to produce inulin polymer and FOS in situ, and is unique in its distribution of FOS synthesized, ranging from DP2 to DP13. The probiotic bacterium L. gasseri DSM 20243 did not produce any fructan, although we identified a fructansucrase-encoding gene in its genome sequence. Further studies showed that this L. gasseri DSM 20243 gene was prematurely terminated by a stop codon. Exchanging the stop codon for a glutamine codon resulted in a recombinant enzyme producing inulin and FOS. The three recombinant fructansucrase enzymes characterized from three different L. gasseri strains have very similar primary protein structures, yet synthesize different fructan products. An interesting feature of the L. gasseri strains is that they were unable to ferment raffinose, whereas their respective recombinant enzymes converted raffinose into fructan and FOS.
Cooperative interaction between retinoic acid receptor-α and estrogen receptor in breast cancer
Authors: Ross-Innes Caryn S. , Stark Rory , Holmes Kelly A. , Schmidt Dominic , Spyrou Christiana , Russell Roslin , Massie Charlie E. , Vowler Sarah L. , Eldridge Matthew , Carroll Jason S.
Published: January 2010

Retinoic acid receptor-α (RARα) is a known estrogen target gene in breast cancer cells. The consequence of RARα induction by estrogen was previously unknown. We now show that RARα is required for efficient estrogen receptor-α (ER)-mediated transcription and cell proliferation. RARα can interact with ER-binding sites, but this occurs in an ER-dependent manner, providing a novel role for RARα that is independent of its classic role. We show, on a genome-wide scale, that RARα and ER can co-occupy regulatory regions together within the chromatin. This transcriptionally active co-occupancy and dependency occurs when exposed to the predominant breast cancer hormone, estrogen—an interaction that is promoted by the estrogen–ER induction of RARα. These findings implicate RARα as an essential component of the ER complex, potentially by maintaining ER–cofactor interactions, and suggest that different nuclear receptors can cooperate for effective transcriptional activity in breast cancer cells.
A feedback loop mediated by degradation of an inhibitor is required to initiate neuronal differentiation
Authors: Sobieszczuk Dorothy F. , Poliakov Alexei , Xu Qiling , Wilkinson David G.
Published: January 2010

Neuronal differentiation is regulated by proneural genes that promote neurogenesis and inhibitory mechanisms that maintain progenitors. This raises the question of how the up-regulation of proneural genes required to initiate neurogenesis occurs in the presence of such inhibition. We carried out loss and gain of gene function, an interaction screen for binding partners, and biochemical analyses to uncover the regulation, developmental role, and mechanism of action of a ubiquitination adaptor protein, Btbd6a (BTB domain containing 6a). We find that the proneural geneneurog1up-regulatesbtbd6a, which in turn is required for up-regulation ofneurog1. Btbd6a is an adaptor for the Cul3 ubiquitin ligase complex, and we find that it binds to the transcriptional repressor Plzf (promyelocytic leukemia zinc finger). Btbd6a promotes the relocation of Plzf from nucleus to cytoplasm and targets Plzf for ubiquitination and degradation.plzfais expressed widely in the neural epithelium; when overexpressed, it inhibits neurogenesis, and this inhibition is reversed bybtbd6a. The antagonism of endogenousplzfabybtbd6ais required for neurogenesis, since the block in neuronal differentiation caused bybtbd6aknockdown is alleviated byplzfaknockdown. These findings reveal a feedback loop mediated by degradation of an inhibitor that is essential for progenitors to undergo the transition to neuronal differentiation.
A novel, noncanonical mechanism of cytoplasmic polyadenylation operates in Drosophila embryogenesis
Authors: Coll Olga , Villalba Ana , Bussotti Giovanni , Notredame Cedric , Gebauer Fátima
Published: January 2010

Cytoplasmic polyadenylation is a widespread mechanism to regulate mRNA translation that requires two sequences in the 3′ untranslated region (UTR) of vertebrate substrates: the polyadenylation hexanucleotide, and the cytoplasmic polyadenylation element (CPE). Using a cell-free Drosophila system, we show that these signals are not relevant for Toll polyadenylation but, instead, a “polyadenylation region” (PR) is necessary. Competition experiments indicate that PR-mediated polyadenylation is required for viability and is mechanistically distinct from the CPE/hexanucleotide-mediated process. These data indicate that Toll mRNA is polyadenylated by a noncanonical mechanism, and suggest that a novel machinery functions for cytoplasmic polyadenylation during Drosophila embryogenesis.
Genome-wide discovery of human heart enhancers
Authors: Narlikar Leelavati , Sakabe Noboru J. , Blanski Alexander A. , Arimura Fabio E. , Westlund John M. , Nobrega Marcelo A. , Ovcharenko Ivan
Published: January 2010

The various organogenic programs deployed during embryonic development rely on the precise expression of a multitude of genes in time and space. Identifying thecis-regulatory elements responsible for this tightly orchestrated regulation of gene expression is an essential step in understanding the genetic pathways involved in development. We describe a strategy to systematically identify tissue-specificcis-regulatory elements that share combinations of sequence motifs. Using heart development as an experimental framework, we employed a combination of Gibbs sampling and linear regression to build a classifier that identifies heart enhancers based on the presence and/or absence of various sequence features, including known and putative transcription factor (TF) binding specificities. In distinguishing heart enhancers from a large pool of random noncoding sequences, the performance of our classifier is vastly superior to four commonly used methods, with an accuracy reaching 92% in cross-validation. Furthermore, most of the binding specificities learned by our method resemble the specificities of TFs widely recognized as key players in heart development and differentiation, such as SRF, MEF2, ETS1, SMAD, and GATA. Using our classifier as a predictor, a genome-wide scan identified over 40,000 novel human heart enhancers. Although the classifier used no gene expression information, these novel enhancers are strongly associated with genes expressed in the heart. Finally, in vivo tests of our predictions in mouse and zebrafish achieved a validation rate of 62%, significantly higher than what is expected by chance. These results support the existence of underlyingcis-regulatory codes dictating tissue-specific transcription in mammalian genomes and validate our enhancer classifier strategy as a method to uncover these regulatory codes.
The relationship between mandatory and other food label information
Authors: Stuart Stephen A.
Published: January 2010

Purpose

This pilot study for a larger research project aims to quantify and categorise elements of food label information and establishes an indicative physical relationship between mandatory and other information thereby articulating the relative balance between information intended to inform healthy dietary choices and that intended to perform other functions such as aiding purchase decisions.

Design/methodology/approach

The methodology employs quantitative content analysis performed on a number of different canned food labels (n=9).

Findings

Findings indicate the amount of available space on labels devoted to mandatory information ranged between 17 and 31 per cent, whilst the amount allocated to commercial information ranged between 18 and 45 per cent. Unoccupied space varies between 32 and 54 per cent. This indicates there is an imbalance between mandatory and commercial information, with the weighting in favour of the latter.

Research limitations/implications

The small sample size precludes generalization.

Practical implications

An extended version of this research could influence government and corporate policy in establishing a balance between the prominence given to different categories of label information, favouring that which is more “health positive”. Alternately, information could be presented in a larger format, thereby assisting a wider range of consumers to make healthy and informed dietary choices: both outcomes have positive health implications for the population. Another outcome is the formal classification of label information elements thereby enabling clearer comparisons to be made between consumers' food label interactions.

Originality/value

This is the first time content analysis has been conducted on food labels. The paper is also unique in proposing a formal taxonomy for food label information. It has value for those working on policy issues.
Olives, hospitality and tourism: a Western Australian perspective
Authors: Duarte Alonso Abel
Published: January 2010

Purpose

The purpose of this paper is to examine the links between olive growing, hospitality and tourism in an emerging olive growing region, as well as challenges olive grove operators face.

Design/methodology/approach

A qualitative approach is taken in the form of face‐to‐face and telephone interviews among 23 olive grove operators in Western Australia from a sample of 33 operations identified.

Findings

Almost half of the respondents indicated being open to the public in some form, including cellar door sales and hospitality facilities, such as a café. Other respondents are currently in the process of developing hospitality facilities or plan to be associated to tourism. However, some responses identified existing marketing issues and outside competition from cheaper products as current constraints.

Research limitations/implications

That only 23 respondents participated in the study does clearly limit the generalisability of the findings in regards to olive growing in Western Australian or elsewhere. Despite this limitation, this exploratory study provides first insights into an unexplored emerging and increasingly multifunctional industry.

Practical implications

In view of some operators' concerns of being able to market their products in the future, the findings illustrate that the mix of strategies combining the olive products, hospitality and/or tourism could have several positive impacts on this emerging industry for those operators willing and able to pursue such paths.

Originality/value

The current developmental stage of olive growing and its potential for further extending into “olive tourism” or related concepts suggests opportunities for future research.
Usage and understanding of food and nutritional labels among Indian consumers
Authors: Singla Manisha
Published: January 2010

Purpose

Nutritional labeling of food products is not mandatory in India at present and the Indian Government is on the verge of introducing a code of conduct for it. The aim of this paper is to provide some initial guidelines for the above‐said purpose so as to have consumer friendly labeling policies.

Design/methodology/approach

A structured questionnaire‐based survey was used for the purpose of the study. A total of 100 respondents were considered for the study. Data were collected from two superstores located in New Delhi.

Findings

Food labels are read by the consumers for brand comparisons and not for consulting nutritional information. Difficult terminology, small font size and inability to understand nutritional labels are the major problems encountered by the consumers. Television, friends, magazines are commonly used for assessing nutritional information. Labels are considered more consumer friendly when benchmarks regarding serving size are provided. Income level, size of household, number of children and age did not play a role in the usage of nutritional labels by the consumers. Consumers with special dietary needs used nutritional labels regularly.

Research limitations/implications

A small sample size is the limitation of the study.

Originality/value

This is the first study of its kind in India. It is valuable for the Indian Government in framing policies regarding nutritional labeling and for imparting nutritional education. It will also help it to draft consumer friendly labels for effective usage.
Variation in the physicochemical characteristics of cashew (Anacardium occidentale L.) apples with maturity
Authors: Yahaya L.E. , Aliyu O.M. , Hammed L.A. , Aroyeun S.O.
Published: January 2010

Purpose

The purpose of this paper is to determine the physicochemical characteristics of yellow and red apples cultivars of cashew. This is with a view to harnessing the quality attributes of the different cultivars of cashew. Parameters investigated include pH, refractive index, specific gravity, vitamin C content, juice astringency, chlorophyll and juice yield.

Design/methodology/approach

The methods of the Association of Official Analytical Chemists (AOAC) are employed in assaying the physicochemical properties, while the astringency is determined spectrophotometrically according to standard methods.

Findings

Results showed that percentage juice yield increases linearly with maturity for both cultivars. A maximum of 79.5 per cent is obtained for the yellow apple cultivars, while 74.1 per cent juice yield is obtained in the red apple cultivar. The pH ranged from 3.73‐4.5 and 3.64‐4.55 for red and yellow apple cultivars, respectively, with a marked fall between seven and eight weeks after pollination (WAPo). Specific gravity and refractive index are of the order 0.999‐1.007 and 1.34‐1.89 for both selected samples. Highest refractive index is obtained in red and yellow cultivars at seven and eight WAPo. The changes in ascorbic acid followed a linear pattern and the maximum values of 249.5 mg/100 ml and 185.5 mg/100 ml are obtained for yellow and red apple cultivars, respectively. Meanwhile, the juice astringency level decreased steadily with maturity and at the ninth WAPo, values obtained are 0.47 and 0.86 mg/100 ml tannin for yellow and red apple cultivars, respectively. Generally, pH, astringency, refractive index, juice content, ascorbic acid and chlorophyll contents showed marked variations between six and eight WAPo, confirming physiological maturity and ripening in the crop species.

Originality/value

Cashew farmers and industrialists will know the best time to harvest the crop when the quality is at its peak.
Resistance to organizational change: linking research and practice
Authors: Erwin Dennis G. , Garman Andrew N.
Published: January 2010

Purpose

The purpose of this paper is to study recently published research to identify findings that provide research‐based guidance to organizational change agents and managers in addressing individual resistance to organizational change initiatives.

Design/methodology/approach

The paper examines published research appearing in peer‐reviewed journals since 1998 that focus on exploring individual resistance to organizational change.

Findings

Recent published research provides considerable practical guidance to organizational change agents and managers in understanding and dealing with resistance to change. Recent research examines the cognitive, affective, and behavioral dimensions of individual resistance and how it is influenced by: individual predispositions towards openness and resistance to change; individuals' considerations of threats and benefits of change; communication, understanding, participation, trust in management, management styles, and the nature of relationships with the change agents.

Research limitations/implications

This paper is limited to research articles involving resistance to organizational change published in peer‐reviewed journals from 1998 to 2009. Also, the paper finds that reported research used primarily self‐report questionnaires to gather data, which are quantitatively analyzed. Such a lack of diversity of research methodologies provides a limited perspective of resistance to organizational change that might have been broadened by qualitative and practice‐based methods (e.g. case studies and action research).

Practical implications

A framework is presented linking organizational change research findings to specific change practitioner recommendations. Limitations of recent research are also discussed.

Originality/value

Most studies provide an examination of a limited number of variables influencing resistance to change, and are not necessary designed to provide practical guidance to change practitioners. This paper provides a comprehensive framework of constructs and variables specifically aimed at linking research‐based findings to guidance for change practitioners.