bluuebunny/crossref_metadata_2025 huggingface dataset:
Tug-of-war and the infinity Laplacian
Authors: Peres Yuval , Schramm Oded , Sheffield Scott , Wilson David
Published: October 2008

We prove that every bounded Lipschitz function

F
F

on a subset

Y
Y

of a length space

X
X

admits a tautest extension to

X
X

, i.e., a unique Lipschitz extension

u
:
X
→

R

u:X \rightarrow \mathbb {R}

for which

Lip
U

⁡
u
=

Lip

∂
U

⁡
u

\operatorname {Lip}_U u =\operatorname {Lip}_{\partial U} u

for all open

U
⊂
X
∖
Y

U \subset X\smallsetminus Y

. This was previously known only for bounded domains in

R

n

\mathbb {R}^n

, in which case

u
u

is infinity harmonic; that is, a viscosity solution to

Δ
∞

u
=
0

\Delta _\infty u = 0

, where
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="normal upper Delta Subscript normal infinity Baseline u equals StartAbsoluteValue nabla u EndAbsoluteValue Superscript negative 2 Baseline sigma-summation Underscript i comma j Endscripts u Subscript x Sub Subscript i Subscript Baseline u Subscript x Sub Subscript i Subscript x Sub Subscript j Subscript Baseline u Subscript x Sub Subscript j Subscript Baseline period">

Δ
∞

u
=

|

∇
u

|

−
2

∑

i
,
j

u

x
i

u

x
i

x
j

u

x
j

.

\Delta _\infty u = |\nabla u|^{-2} \sum _{i,j} u_{x_i} u_{x_ix_j} u_{x_j}.

\]
We also prove the first general uniqueness results for

Δ

∞

u
=
g

\Delta _{\infty } u = g

on bounded subsets of

R

n

\mathbb {R}^n

(when

g
g

is uniformly continuous and bounded away from

0
0

) and analogous results for bounded length spaces. The proofs rely on a new game-theoretic description of

u
u

. Let

u
ε

(
x
)

u^\varepsilon (x)

be the value of the following two-player zero-sum game, called tug-of-war: fix

x
0

=
x
∈
X
∖
Y

x_0=x\in X \smallsetminus Y

. At the

k

t
h

k^{\mathrm {th}}

turn, the players toss a coin and the winner chooses an

x
k

x_k

with

d
(

x
k

,

x

k
−
1

)
>
ε

d(x_k, x_{k-1})> \varepsilon

. The game ends when

x
k

∈
Y

x_k \in Y

, and player I’s payoff is
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper F left-parenthesis x Subscript k Baseline right-parenthesis minus StartFraction epsilon squared Over 2 EndFraction sigma-summation Underscript i equals 0 Overscript k minus 1 Endscripts g left-parenthesis x Subscript i Baseline right-parenthesis">

F
(

x
k

)
−

ε
2

2

∑

i
=
0

k
−
1

g
(

x
i

)

F(x_k) - \frac {\varepsilon ^2}{2}\sum _{i=0}^{k-1} g(x_i)

. We show that

‖

u
ε

−
u

‖

∞

→
0

\|u^\varepsilon - u\|_{\infty } \to 0

. Even for bounded domains in

R

n

\mathbb {R}^n

, the game theoretic description of infinity harmonic functions yields new intuition and estimates; for instance, we prove power law bounds for infinity harmonic functions in the unit disk with boundary values supported in a

δ
\delta

-neighborhood of a Cantor set on the unit circle.
Exponential Thurston maps and limits of quadratic differentials
Authors: Hubbard John , Schleicher Dierk , Shishikura Mitsuhiro
Published: October 2008

We give a topological characterization of postsingularly finite topological exponential maps, i.e., universal covers

g
:

C

→

C

∖
{
0
}

g\colon \mathbb {C}\to \mathbb {C}\setminus \{0\}

such that

0
0

has a finite orbit. Such a map either is Thurston equivalent to a unique holomorphic exponential map

λ

e
z

\lambda e^z

or it has a topological obstruction called a degenerate Levy cycle. This is the first analog of Thurston’s topological characterization theorem of rational maps, as published by Douady and Hubbard, for the case of infinite degree.

One main tool is a theorem about the distribution of mass of an integrable quadratic differential with a given number of poles, providing an almost compact space of models for the entire mass of quadratic differentials. This theorem is given for arbitrary Riemann surfaces of finite type in a uniform way.
Compressed sensing and best 𝑘-term approximation
Authors: Cohen Albert , Dahmen Wolfgang , DeVore Ronald
Published: October 2008

Compressed sensing is a new concept in signal processing where one seeks to minimize the number of measurements to be taken from signals while still retaining the information necessary to approximate them well. The ideas have their origins in certain abstract results from functional analysis and approximation theory by Kashin but were recently brought into the forefront by the work of Candès, Romberg, and Tao and of Donoho who constructed concrete algorithms and showed their promise in application. There remain several fundamental questions on both the theoretical and practical sides of compressed sensing. This paper is primarily concerned with one of these theoretical issues revolving around just how well compressed sensing can approximate a given signal from a given budget of fixed linear measurements, as compared to adaptive linear measurements. More precisely, we consider discrete signals

x
∈

R

N

x\in \mathbb {R}^N

, allocate

n
>
N

n>N

linear measurements of

x
x

, and we describe the range of

k
k

for which these measurements encode enough information to recover

x
x

in the sense of

ℓ
p

\ell _p

to the accuracy of best

k
k

-term approximation. We also consider the problem of having such accuracy only with high probability.
The structure of locally finite varieties with polynomially many models
Authors: Idziak Paweł , McKenzie Ralph , Valeriote Matthew
Published: October 2008

We prove that a locally finite variety has at most polynomially many (in

k
k

) non-isomorphic

k
k

–generated algebras if and only if it decomposes into a varietal product of an affine variety over a ring of finite representation type, and a sequence of strongly Abelian varieties equivalent to matrix powers of varieties of

H
H

-sets, with constants, for various finite groups

H
H

.
Galectin-7 in the Control of Epidermal Homeostasis after Injury
Authors: Gendronneau Gaëlle , Sidhu Sukhvinder S. , Delacour Delphine , Dang Tien , Calonne Chloé , Houzelstein Denis , Magnaldo Thierry , Poirier Françoise
Published: October 2008

Galectins, a family of β-galactoside binding lectins, have recently emerged as novel regulators of tissue homeostasis. Galectin-7 is predominantly expressed in stratified epithelia, especially in epidermis. We report here the generation of galectin-7–deficient mice that are viable and do not display phenotypical abnormalities in skin structure or expression of epidermal markers. However, these mice show unique defects in the maintenance of epidermal homeostasis in response to environmental challenges. First, after UVB irradiation in vivo, the apoptotic response is prematurely triggered and lasts longer in the mutant epidermis. This result contrasts with the proapoptotic role that had been proposed for galectin-7. Second, wound-healing experiments in vivo revealed that galectin-7–deficient mice displayed a reduced reepithelialization potential compared with wild-type littermates. This effect could be attributed to a defect in cell migration. Because galectin-7 is located in the podosomes of keratinocytes migrating out of skin explants in culture, we propose that this glycan-binding protein may directly influence cell/extracellular matrix interactions. Finally, we also detected an unexpected intense hyperproliferative reaction consecutive to both types of stress in galectin-7–deficient mice. Together, these studies provide the first genetic evidence showing that galectin-7 can modulate keratinocyte apoptosis, proliferation, and migration during skin repair.
The Scaffold Protein POSH Regulates Axon Outgrowth
Authors: Taylor Jennifer , Chung Kwan-Ho , Figueroa Claudia , Zurawski Jonathan , Dickson Heather M. , Brace E. J. , Avery Adam W. , Turner David L. , Vojtek Anne B.
Published: October 2008

How scaffold proteins integrate signaling pathways with cytoskeletal components to drive axon outgrowth is not well understood. We report here that the multidomain scaffold protein Plenty of SH3s (POSH) regulates axon outgrowth. Reduction of POSH function by RNA interference (RNAi) enhances axon outgrowth in differentiating mouse primary cortical neurons and in neurons derived from mouse P19 cells, suggesting POSH negatively regulates axon outgrowth. Complementation analysis reveals a requirement for the third Src homology (SH) 3 domain of POSH, and we find that the actomyosin regulatory protein Shroom3 interacts with this domain of POSH. Inhibition of Shroom3 expression by RNAi leads to increased process lengths, as observed for POSH RNAi, suggesting that POSH and Shroom function together to inhibit process outgrowth. Complementation analysis and interference of protein function by dominant-negative approaches suggest that Shroom3 recruits Rho kinase to inhibit process outgrowth. Furthermore, inhibition of myosin II function reverses the POSH or Shroom3 RNAi phenotype, indicating a role for myosin II regulation as a target of the POSH–Shroom complex. Collectively, these results suggest that the molecular scaffold protein POSH assembles an inhibitory complex that links to the actin–myosin network to regulate neuronal process outgrowth.
Ribosome-associated Complex Binds to Ribosomes in Close Proximity of Rpl31 at the Exit of the Polypeptide Tunnel in Yeast
Authors: Peisker Kristin , Braun Daniel , Wölfle Tina , Hentschel Jendrik , Fünfschilling Ursula , Fischer Gunter , Sickmann Albert , Rospert Sabine
Published: October 2008

Ribosome-associated complex (RAC) consists of the Hsp40 homolog Zuo1 and the Hsp70 homolog Ssz1. The chaperone participates in the biogenesis of newly synthesized polypeptides. Here we have identified yeast Rpl31, a component of the large ribosomal subunit, as a contact point of RAC at the polypeptide tunnel exit. Rpl31 is encoded by RPL31a and RPL31b, two closely related genes. Δrpl31aΔrpl31b displayed slow growth and sensitivity to low as well as high temperatures. In addition, Δrpl31aΔrpl31b was highly sensitive toward aminoglycoside antibiotics and suffered from defects in translational fidelity. With the exception of sensitivity at elevated temperature, the phenotype resembled yeast strains lacking one of the RAC subunits or Rpl39, another protein localized at the tunnel exit. Defects of Δrpl31aΔrpl31bΔzuo1 did not exceed that of Δrpl31aΔrpl31b or Δzuo1. However, the combined deletion of RPL31a, RPL31b, and RPL39 was lethal. Moreover, RPL39 was a multicopy suppressor, whereas overexpression of RAC failed to rescue growth defects of Δrpl31aΔrpl31b. The findings are consistent with a model in that Rpl31 and Rpl39 independently affect a common ribosome function, whereas Rpl31 and RAC are functionally interdependent. Rpl31, while not essential for binding of RAC to the ribosome, might be involved in proper function of the chaperone complex.
Sentan: A Novel Specific Component of the Apical Structure of Vertebrate Motile Cilia
Authors: Kubo Akiharu , Yuba-Kubo Akiko , Tsukita Sachiko , Tsukita Shoichiro , Amagai Masayuki
Published: October 2008

Human respiratory and oviductal cilia have specific apical structures characterized by a narrowed distal portion and a ciliary crown. These structures are conserved among vertebrates that have air respiration systems; however, the molecular components of these structures have not been defined, and their functions are unknown. To identify the molecular component(s) of the cilia apical structure, we screened EST libraries to identify gene(s) that are exclusively expressed in ciliated tissues, are transcriptionally up-regulated during in vitro ciliogenesis, and are not expressed in testis (because sperm flagella have no such apical structures). One of the identified gene products, named sentan, was localized to the distal tip region of motile cilia. Using anti-sentan polyclonal antibodies and electron microscopy, sentan was shown to localize exclusively to the bridging structure between the cell membrane and peripheral singlet microtubules, which specifically exists in the narrowed distal portion of cilia. Exogenously expressed sentan showed affinity for the membrane protrusions, and a protein–lipid binding assay revealed that sentan bound to phosphatidylserine. These findings suggest that sentan is the first molecular component of the ciliary tip to bridge the cell membrane and peripheral singlet microtubules, making the distal portion of the cilia narrow and stiff to allow for better airway clearance or ovum transport.
Causes and consequences of life-history variation in North American stocks of Pacific cod
Authors: Ormseth Olav A. , Norcross Brenda L.
Published: October 2008

Ormseth, O. A., and Norcross, B. L. 2009. Causes and consequences of life-history variation in North American stocks of Pacific cod. – ICES Journal of Marine Science, 66: 349–357. Life-history strategies of four Pacific cod (Gadus macrocephalus) stocks in the eastern North Pacific Ocean are outlined. Southern stocks grew and matured quicker, but reached smaller maximum size and had shorter lifespans than northern stocks. The trade-offs resulted in similar lifetime reproductive success among all stocks. Growth was highly dependent on latitude, but not on temperature, possibly because of differences in the duration of the growing season. Comparisons with Atlantic cod (Gadus morhua) revealed similar latitude/growth relationships among Atlantic cod stocks grouped by geographic region. In Pacific cod, greater size and longevity in the north appeared to be adaptations to overcome environmental constraints on growth and to maintain fitness. An egg production-per-recruit model suggested that the life-history strategy of northern Pacific cod stocks made them less resilient to fishing activity and age truncation than southern stocks.
Predicting transcription factor specificity with all-atom models
Authors: Rahi Sahand J. , Virnau Peter , Mirny Leonid A. , Kardar Mehran
Published: October 2008

The binding of a transcription factor (TF) to a DNA operator site can initiate or repress the expression of a gene. Computational prediction of sites recognized by a TF has traditionally relied upon knowledge of several cognate sites, rather than an ab initio approach. Here, we examine the possibility of using structure-based energy calculations that require no knowledge of bound sites but rather start with the structure of a protein–DNA complex. We study the PurR Escherichia coli TF, and explore to which extent atomistic models of protein–DNA complexes can be used to distinguish between cognate and noncognate DNA sites. Particular emphasis is placed on systematic evaluation of this approach by comparing its performance with bioinformatic methods, by testing it against random decoys and sites of homologous TFs. We also examine a set of experimental mutations in both DNA and the protein. Using our explicit estimates of energy, we show that the specificity for PurR is dominated by direct protein–DNA interactions, and weakly influenced by bending of DNA.
Intangibility in intertemporal choice
Authors: Rick Scott , Loewenstein George
Published: October 2008

Since the advent of the discounted utility (DU) model, economists have thought about intertemporal choice in very specific terms. DU assumes that people make
explicit trade-offs
between costs and benefits occurring at different points in time. While this explicit trade-off perspective is simple and tractable, and has stimulated productive research, it does not provide a very realistic representation of a wide range of the most important intertemporal trade-offs that people face in daily life. If one considers the most important and commonly discussed examples of intertemporal choices, a striking pattern emerges: in almost all cases, early outcomes tend to be concrete (e.g. purchasing this latte), but later outcomes tend to be much less tangible (e.g. the unknown item that could have been purchased later with the money spent on this latte). We propose that people rely on anticipatory emotions as a proxy for intangible outcomes when trade-offs are implicit. This paper reviews neuroeconomic evidence that has begun to elucidate the role of anticipatory emotions in decisions involving intangible outcomes. Although most progress has been made in the domain of spending and saving, we discuss how the existing neuroeconomic research could be extended to other domains where trade-offs are ill defined.
Anticipatory affect: neural correlates and consequences for choice
Authors: Knutson Brian , Greer Stephanie M
Published: October 2008

‘Anticipatory affect’ refers to emotional states that people experience while anticipating significant outcomes. Historically, technical limitations have made it difficult to determine whether anticipatory affect influences subsequent choice. Recent advances in the spatio-temporal resolution of functional magnetic resonance imaging, however, now allow researchers to visualize changes in neural activity seconds before choice occurs. We review evidence that activation in specific brain circuits changes during anticipation of monetary incentives, that this activation correlates with affective experience and that activity in these circuits may influence subsequent choice. Specifically, an activation likelihood estimate meta-analysis of cued response studies indicates that nucleus accumbens (NAcc) activation increases during gain anticipation relative to loss anticipation, while anterior insula activation increases during both loss and gain anticipation. Additionally, anticipatory NAcc activation correlates with self-reported positive arousal, whereas anterior insula activation correlates with both self-reported negative and positive arousal. Finally, NAcc activation precedes the purchase of desirable products and choice of high-risk gambles, whereas anterior insula activation precedes the rejection of overpriced products and choice of low-risk gambles. Together, these findings support a neurally plausible framework for understanding how anticipatory affect can influence choice.
The role of social cognition in decision making
Authors: Frith Chris D , Singer Tania
Published: October 2008

Successful decision making in a social setting depends on our ability to understand the intentions, emotions and beliefs of others. The mirror system allows us to understand other people's motor actions and action intentions. ‘Empathy’ allows us to understand and share emotions and sensations with others. ‘Theory of mind’ allows us to understand more abstract concepts such as beliefs or wishes in others. In all these cases, evidence has accumulated that we use the specific neural networks engaged in processing mental states in ourselves to understand the same mental states in others. However, the magnitude of the brain activity in these shared networks is modulated by contextual appraisal of the situation or the other person. An important feature of decision making in a social setting concerns the interaction of reason and emotion. We consider four domains where such interactions occur: our sense of fairness, altruistic punishment, trust and framing effects. In these cases, social motivations and emotions compete with each other, while higher-level control processes modulate the interactions of these low-level biases.
Cortical mechanisms for reinforcement learning in competitive games
Authors: Seo Hyojung , Lee Daeyeol
Published: October 2008

Game theory analyses optimal strategies for multiple decision makers interacting in a social group. However, the behaviours of individual humans and animals often deviate systematically from the optimal strategies described by game theory. The behaviours of rhesus monkeys (Macaca mulatta) in simple zero-sum games showed similar patterns, but their departures from the optimal strategies were well accounted for by a simple reinforcement-learning algorithm. During a computer-simulated zero-sum game, neurons in the dorsolateral prefrontal cortex often encoded the previous choices of the animal and its opponent as well as the animal's reward history. By contrast, the neurons in the anterior cingulate cortex predominantly encoded the animal's reward history. Using simple competitive games, therefore, we have demonstrated functional specialization between different areas of the primate frontal cortex involved in outcome monitoring and action selection. Temporally extended signals related to the animal's previous choices might facilitate the association between choices and their delayed outcomes, whereas information about the choices of the opponent might be used to estimate the reward expected from a particular action. Finally, signals related to the reward history might be used to monitor the overall success of the animal's current decision-making strategy.
Neuroethology of reward and decision making
Authors: Watson Karli K , Platt Michael L
Published: October 2008

Ethology, the evolutionary science of behaviour, assumes that natural selection shapes behaviour and its neural substrates in humans and other animals. In this view, the nervous system of any animal comprises a suite of morphological and behavioural adaptations for solving specific information processing problems posed by the physical or social environment. Since the allocation of behaviour often reflects economic optimization of evolutionary fitness subject to physical and cognitive constraints, neurobiological studies of reward, punishment, motivation and decision making will profit from an appreciation of the information processing problems confronted by animals in their natural physical and social environments.
The role of the striatum in aversive learning and aversive prediction errors
Authors: Delgado Mauricio R , Li Jian , Schiller Daniela , Phelps Elizabeth A
Published: October 2008

Neuroeconomic studies of decision making have emphasized reward learning as critical in the representation of value-driven choice behaviour. However, it is readily apparent that punishment and aversive learning are also significant factors in motivating decisions and actions. In this paper, we review the role of the striatum and amygdala in affective learning and the coding of aversive prediction errors (PEs). We present neuroimaging results showing aversive PE-related signals in the striatum in fear conditioning paradigms with both primary (shock) and secondary (monetary loss) reinforcers. These results and others point to the general role for the striatum in coding PEs across a broad range of learning paradigms and reinforcer types.
The Transcript and Metabolite Networks Affected by the Two Clades of Arabidopsis Glucosinolate Biosynthesis Regulators
Authors: Malitsky Sergey , Blum Eyal , Less Hadar , Venger Ilya , Elbaz Moshe , Morin Shai , Eshed Yuval , Aharoni Asaph
Published: October 2008

In this study, transcriptomics and metabolomics data were integrated in order to examine the regulation of glucosinolate (GS) biosynthesis in Arabidopsis (Arabidopsis thaliana) and its interface with pathways of primary metabolism. Our genetic material for analyses were transgenic plants overexpressing members of two clades of genes (ALTERED TRYPTOPHAN REGULATION1 [ATR1]-like and MYB28-like) that regulate the aliphatic and indole GS biosynthetic pathways (AGs and IGs, respectively). We show that activity of these regulators is not restricted to the metabolic space surrounding GS biosynthesis but is tightly linked to more distal metabolic networks of primary metabolism. This suggests that with similarity to the regulators we have investigated here, other factors controlling pathways of secondary metabolism might also control core pathways of central metabolism. The relatively broad view of transcripts and metabolites altered in transgenic plants overexpressing the different factors underlined novel links of GS metabolism to additional metabolic pathways, including those of jasmonic acid, folate, benzoic acid, and various phenylpropanoids. It also revealed transcriptional and metabolic hubs in the “distal” network of metabolic pathways supplying precursors to GS biosynthesis and that overexpression of the ATR1-like clade genes has a much broader effect on the metabolism of indolic compounds than described previously. While the reciprocal, negative cross talk between the methionine and tryptophan pathways that generate GSs in Arabidopsis has been suggested previously, we now show that it is not restricted to AGs and IGs but includes additional metabolites, such as the phytoalexin camalexin. Combining the profiling data of transgenic lines with gene expression correlation analysis allowed us to propose a model of how the balance in the metabolic network is maintained by the GS biosynthesis regulators. It appears that ATR1/MYB34 is an important mediator between the gene activities of the two clades. While it is very similar to the ATR1-like clade members in terms of downstream gene targets, its expression is highly correlated with that of the MYB28-like clade members. Finally, we used the unique transgenic plants obtained here to show that AGs are likely more potent deterrents of the whitefly Bemisia tabaci compared with IGs. The influence on insect behavior raises an important question for future investigation of the functional aspect of our initial finding, which pointed to enriched expression of the MYB28-like clade genes in the abaxial domain of the Arabidopsis leaf.
Decreased Expression of Cytosolic Pyruvate Kinase in Potato Tubers Leads to a Decline in Pyruvate Resulting in an in Vivo Repression of the Alternative Oxidase
Authors: Oliver Sandra N. , Lunn John E. , Urbanczyk-Wochniak Ewa , Lytovchenko Anna , van Dongen Joost T. , Faix Benjamin , Schmälzlin Elmar , Fernie Alisdair R. , Geigenberger Peter
Published: October 2008

The aim of this work was to investigate the effect of decreased cytosolic pyruvate kinase (PKc) on potato (Solanum tuberosum) tuber metabolism. Transgenic potato plants with strongly reduced levels of PKc were generated by RNA interference gene silencing under the control of a tuber-specific promoter. Metabolite profiling showed that decreased PKc activity led to a decrease in the levels of pyruvate and some other organic acids involved in the tricarboxylic acid cycle. Flux analysis showed that this was accompanied by changes in carbon partitioning, with carbon flux being diverted from glycolysis toward starch synthesis. However, this metabolic shift was relatively small and hence did not result in enhanced starch levels in the tubers. Although total respiration rates and the ATP to ADP ratio were largely unchanged, transgenic tubers showed a strong decrease in the levels of alternative oxidase (AOX) protein and a corresponding decrease in the capacity of the alternative pathway of respiration. External feeding of pyruvate to tuber tissue or isolated mitochondria resulted in activation of the AOX pathway, both in the wild type and the PKc transgenic lines, providing direct evidence for the regulation of AOX by changes in pyruvate levels. Overall, these results provide evidence for a crucial role of PKc in the regulation of pyruvate levels as well as the level of the AOX in heterotrophic plant tissue, and furthermore reveal that these parameters are interlinked in vivo.
How well can the accuracy of comparative protein structure models be predicted?
Authors: Eramian David , Eswar Narayanan , Shen Min‐Yi , Sali Andrej
Published: October 2008

Comparative structure models are available for two orders of magnitude more protein sequences than are experimentally determined structures. These models, however, suffer from two limitations that experimentally determined structures do not: They frequently contain significant errors, and their accuracy cannot be readily assessed. We have addressed the latter limitation by developing a protocol optimized specifically for predicting the Cα root‐mean‐squared deviation (RMSD) and native overlap (NO3.5Å) errors of a model in the absence of its native structure. In contrast to most traditional assessment scores that merely predict one model is more accurate than others, this approach quantifies the error in an absolute sense, thus helping to determine whether or not the model is suitable for intended applications. The assessment relies on a model‐specific scoring function constructed by a support vector machine. This regression optimizes the weights of up to nine features, including various sequence similarity measures and statistical potentials, extracted from a tailored training set of models unique to the model being assessed: If possible, we use similarly sized models with the same fold; otherwise, we use similarly sized models with the same secondary structure composition. This protocol predicts the RMSD and NO3.5Å errors for a diverse set of 580,317 comparative models of 6174 sequences with correlation coefficients (r) of 0.84 and 0.86, respectively, to the actual errors. This scoring function achieves the best correlation compared to 13 other tested assessment criteria that achieved correlations ranging from 0.35 to 0.71.
Antiangiogenesis in haematological malignancies
Authors: Li William W. , Hutnik Michelle , Gehr Gerald
Published: October 2008

Angiogenesis, the growth of new capillary blood vessels, is a central regulator of cancer growth, and a validated target for cancer therapy. The antiangiogenic agents in clinical use target one or more cellular pathways involved in the cascade of vascular growth. In haematological malignancies, angiogenesis occurs within a bone marrow ecosystem comprised of closely apposed malignant cells, endothelial cells, pericytes, fibroblasts, endothelial progenitor cells, dendritic cells, and extracellular matrix. Inhibition of angiogenesis therefore blocks not only the delivery of oxygen and micronutrients to cancer cells, but also disrupts the interdependency of these cellular players and the paracrine effects they exert to maintain the malignant phenotype. Agents such as thalidomide, lenalidomide, bortezomib, and bevacizumab, have demonstrated clinical activity in myeloma, myelodysplastic syndrome, and leukaemias. In leukaemia, vascular endothelial growth factor (VEGF) is emerging as a compelling biological target for therapy, as well as a potential predictive marker for disease relapse. Initial clinical studies suggest that the anti‐VEGF strategies may advance the primary, sequential or adjunctive treatment for leukaemia, and establish the basis for other potential antiangiogenic strategies in haematological malignancies.
Prospective monitoring of BCR‐ABL1 transcript levels in patients with Philadelphia chromosome‐positive acute lymphoblastic leukaemia undergoing imatinib‐combined chemotherapy
Authors: Yanada Masamitsu , Sugiura Isamu , Takeuchi Jin , Akiyama Hideki , Maruta Atsuo , Ueda Yasunori , Usui Noriko , Yagasaki Fumiharu , Yujiri Toshiaki , Takeuchi Makoto , Nishii Kazuhiro , Kimura Yukihiko , Miyawaki Shuichi , Narimatsu Hiroto , Miyazaki Yasushi , Ohtake Shigeki , Jinnai Itsuro , Matsuo Keitaro , Naoe Tomoki , Ohno Ryuzo ,   for the Japan Adult Leukemia Study Group
Published: October 2008

The clinical significance of minimal residual disease (MRD) is uncertain in patients with Philadelphia chromosome‐positive acute lymphoblastic leukaemia (Ph+ ALL) treated with imatinib‐combined chemotherapy. Here we report the results of prospective MRD monitoring in 100 adult patients. Three hundred and sixty‐seven follow‐up bone marrow samples, collected at predefined time points during a uniform treatment protocol, were analysed for BCR‐ABL1 transcripts by quantitative reverse transcription polymerase chain reaction. Ninety‐seven patients (97%) achieved complete remission (CR), and the relapse‐free survival (RFS) rate was 46% at 3 years. Negative MRD at the end of induction therapy was not associated with longer RFS or a lower relapse rate (P = 0·800 and P = 0·964 respectively). Twenty‐nine patients showed MRD elevation during haematological CR. Of these, 10 of the 16 who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) in first CR were alive without relapse at a median of 2·9 years after transplantation, whereas 12 of the 13 who had not undergone allogeneic HSCT experienced a relapse. These results demonstrate that, in Ph+ ALL patients treated with imatinib‐combined chemotherapy, rapid molecular response is not associated with a favourable prognosis, and that a single observation of elevated MRD is predictive of subsequent relapse, but allogeneic HSCT can override its adverse effect.
In vivo anti‐myeloma activity and modulation of gene expression profile induced by valproic acid, a histone deacetylase inhibitor
Authors: Neri Paola , Tagliaferri Pierosandro , Di Martino Maria Teresa , Calimeri Teresa , Amodio Nicola , Bulotta Alessandra , Ventura Monica , Eramo Pasqua Orietta , Viscomi Caterina , Arbitrio Mariamena , Rossi Marco , Caraglia Michele , Munshi Nikhil C. , Anderson Kenneth C. , Tassone Pierfrancesco
Published: October 2008

Valproic acid (VPA) is a well‐tolerated anticonvulsant that exerts anti‐tumour activity as a histone deacetylase inhibitor. This study investigated the in vitro and in vivo activity of VPA against multiple myeloma (MM) cells. In vitro exposure of interleukin‐6‐dependent or ‐independent MM cells to VPA inhibited cell proliferation in a time‐ and dose‐dependent manner and induced apoptosis. In a cohort of severe combined immunodeficiency mice bearing human MM xenografts, VPA induced tumour growth inhibition and survival advantage in treated animals versus controls. Flow cytometric analysis performed on MM cells from excised tumours showed increase of G0–G1 and a decreased G2/M‐ and S‐phase following VPA treatment, indicating in vivo effects of VPA on cell cycle regulation. Gene expression profiling of MM cells exposed to VPA showed downregulation of genes involved in cell cycle progression, DNA replication and transcription, as well as upregulation of genes implicated in apoptosis and chemokine pathways. Pathfinder analysis of gene array data identified cell growth, cell cycle, cell death, as well as DNA replication and repair as the most important signalling networks modulated by VPA. Taken together, our data provide the preclinical rationale for VPA clinical evaluation as a single agent or in combination, to improve patient outcome in MM.
Hepatitis B–Hepatitis C seroprevalences and blunt–penetrating object injuries in housekeepers in Turkey: a survey study
Authors: Özer Zeynep C , Efe Emine , Oncel Selma , Taskinsoy Halime , Ulker Mustan
Published: October 2008

Aim.  This study aims to identify housekeepers’ use of protective measures, provide data about hepatitis B virus (HBV) and hepatitis C virus (HCV) seroprevalences and HBV immunisation, and investigate blunt–penetrating injuries in patient care services, routine cleaning services and orderly services.

Background.  Hospitals have been described as hazardous work environments with an increase in HBV–HCV seroprevalences and blunt–penetrating object injuries. This situation creates great risks and hazards for housekeepers in their jobs.

Design.  Survey.

Methods.  The study population was housekeepers who work in university hospitals. A total of 824 housekeepers were surveyed by using a 20‐item questionnaire. The questionnaire included the sociodemographic characteristics of housekeepers and the risk level of the unit employed. Blood samples were taken from the housekeepers.

Results.  Their mean age was 32·5 years. The majority of the housekeepers (52·5%) were women and graduates of primary school (51·1%). The mean length of employment was 2·6 years, 73% were working on medical/surgical units, 91·2% were working in routine cleaning and 70·9% had been injured with various blunt and penetrating objects while working in the hospital in the past six months. The obtained result for seroprevalence for HBV–HCV was 2·2%. Only 27·5% of the housekeepers had been immunised with Hepatitis B vaccine. A large percentage of housekeepers in this study had used universal precautions.

Conclusion.  This study showed high seroprevalence rates for HBV–HCV and blunt–penetrating object injuries in housekeepers. Therefore, more effort is necessary to increase the use of protective measures against HBV–HCV and blunt–penetrating object injuries in housekeepers.

Relevance to clinical practice.  Hospitals need to take protective measures and implement innovative educational and support programmes organised for specific groups of housekeepers.
A successful way for performing nutritional nursing assessment in older patients
Authors: Söderhamn Ulrika , Söderhamn Olle
Published: October 2008

Aim.  The aim of this study was to obtain increased knowledge and understanding about what can be promoting and facilitating for nurses to perform nutritional nursing assessment in older patients.

Background.  The frequency of older patients at nutritional risk or suffering from undernutrition is high in hospitals. Studies have shown frequent lack of awareness about signs of undernutrition as all patients are, for example, not weighed. Nurses’ descriptions about nutritional problems have also been found to be often vague and unspecific.

Design.  A qualitative design was used.

Methods.  Ten conveniently chosen registered nurses, working with older patients in two hospitals in western Sweden were interviewed. Four of the interviews were performed during 2003 and six during 2006. The interviews were analysed according to a Gadamerian‐based hermeneutic research method.

Results.  The analyses revealed that promoting aspects for performing nutritional nursing assessment in older patients were to get information by dialogues, by observations and controls, by collaboration with other caregivers and professionals and by performing continuous follow‐ups. Necessary conditions, beside knowledge and consciousness about nutritional issues, were to have interest, give time to listen to the patient’s story and furthermore, be sensitive to the patient’s wishes, be able to assess the patient’s motivation to eat and have an ethical awareness.

Conclusions.  A successful way that promoted the performance of nutritional nursing assessment in older patients was to use different approaches as interactive dialogues, observations, controls and collaboration in team. Such a nutritional nursing assessment was an ongoing process during the patient’s hospital stay.

Relevance to clinical practice.  These results highlight that nurses have an important role in identifying eating problems in older patients, which has to be a prioritised issue in the care of older people.
A study on development of a scale to assess nursing students’ performance in clinical settings
Authors: Karayurt Özgul , Mert Hatice , Beser Ayse
Published: October 2008

Aims.  To develop a valid and reliable scale to assess nursing student performance in clinical settings.

Background.  In nursing education, clinical evaluation is important for students, teachers and patients and there is a need to evaluate with valid and reliable scales.

Design.  Instrument development.

Methods.  Data were collected at 2002–2003 and 2003–2004 academic years and 350 evaluations of third and fourth year students formed the study population. In the light of the literature and our experiences, we determined clinical responsibilities of nursing students and wrote 77 items accordingly. These items were discussed twice by 17 teachers at a University School of Nursing and then the items were decreased to 28. Each item was scored between 1 and 10. The structure validity of the scale was evaluated with factor analyses and reliability of the scale with Cronbach’s alpha and item‐to‐total correlation.

Results.  The item‐to‐total correlation coefficient was 0·40 and items were excluded with item‐to‐total correlation coefficient of lower than 0·40. Cronbach’s alpha was 0·97. Three factors with an eigenvalue greater than one were extracted. These factors were ‘nursing process’, ‘professionalism’ and ‘ethical principles’ and their Cronbach’s alpha values were 0·97, 0·94 and 0·87, respectively.

Conclusion.  This scale can be used to evaluate nursing students’ performance in clinical settings.

Relevance to clinical practice.  A valid and reliable tool may allow an objective evaluation of nursing students’ performance in clinical settings.
Outcome of foot examinations in Tanzanian and Swedish diabetic patients, a comparative study
Authors: Smide Bibbi
Published: October 2008

Aims and objectives.  The aim of the current study was to present the outcome of clinical nurse performed foot examinations in a group of Tanzanian diabetic patients and make comparisons with matched Swedish patients.

Background.  Nurses working with diabetic patients in any country need to be familiar with foot problems in diabetic patients to educate patients about foot care.

Design.  A comparative study examining diabetic patients in Tanzania and Sweden with a quantitative approach.

Method.  One hundred and forty‐five diabetic patients in each country were examined. They were matched in gender and age. All patients responded verbally to questions about individual foot‐care and underwent clinical foot examination concerning existing foot lesions, sensitivity testing using Semmes–Weinstein monofilament (5·07) and, vibratory perception using a tuning fork (128 Hz).

Results.  The Tanzanians had more reported foot problems than the Swedes. The latter reported problems due to poorly fitting footwear whilst the Tanzanians reported pain issues of the feet irrespective of footwear. In the Tanzanian group 37 patients presented with peripheral neuropathy (PN), 13 with peripheral vascular disease (PVD) and six had both PN and PVD. In the Swedish group of patients four had PN, three PVD, but none had both PN and PVD. Only 20 Tanzanians reported carrying out self‐inspections of their feet, while 103 Swedes reported doing so.

Conclusions.  Nurse performed foot examinations showed that the Tanzanian diabetic patients in this study had poorer foot status than the Swedish study sample.

Relevance to clinical practice.  Knowledge about foot problems in diabetic patients worldwide will hopefully improve education about self foot‐care and therefore decrease incidence of foot lesions and other foot problems in this cohort.
MinJ (YvjD) is a topological determinant of cell division in Bacillus subtilis
Authors: Patrick Joyce E. , Kearns Daniel B.
Published: October 2008

In Bacillus subtilis, FtsZ ring formation and cell division is favoured at the midcell because the inhibitor proteins MinC and MinD are indirectly restricted to the cell poles by the protein DivIVA. Here we identify MinJ, a topological determinant of medial FtsZ positioning that acts as an intermediary between DivIVA and MinD. Due to unrestricted MinD activity, cells mutated for minJ exhibited pleiotropic defects in homologous recombination, swarming motility and cell division. MinJ restricted MinD activity by localizing MinD to the cell poles through direct protein–protein interaction. MinJ itself localized to cell poles in a manner that was dependent on DivIVA. MinJ is conserved in other low G+C Gram‐positive bacteria and may be an important component of cell division site selection in these organisms.
Intermediate filament‐like proteins in bacteria and a cytoskeletal function in Streptomyces
Authors: Bagchi Sonchita , Tomenius Henrik , Belova Lyubov M. , Ausmees Nora
Published: October 2008

Actin and tubulin cytoskeletons are conserved and widespread in bacteria. A strikingly intermediate filament (IF)‐like cytoskeleton, composed of crescentin, is also present in Caulobacter crescentus and determines its specific cell shape. However, the broader significance of this finding remained obscure, because crescentin appeared to be unique to Caulobacter. Here we demonstrate that IF‐like function is probably a more widespread phenomenon in bacteria. First, we show that 21 genomes of 26 phylogenetically diverse species encoded uncharacterized proteins with a central segmented coiled coil rod domain, which we regarded as a key structural feature of IF proteins and crescentin. Experimental studies of three in silico predicted candidates from Mycobacterium and other actinomycetes revealed a common IF‐like property to spontaneously assemble into filaments in vitro. Furthermore, the IF‐like protein FilP formed cytoskeletal structures in the model actinomycete Streptomyces coelicolor and was needed for normal growth and morphogenesis. Atomic force microscopy of living cells revealed that the FilP cytoskeleton contributed to mechanical fitness of the hyphae, thus closely resembling the function of metazoan IF. Together, the bioinformatic and experimental data suggest that an IF‐like protein architecture is a versatile design that is generally present in bacteria and utilized to perform diverse cytoskeletal tasks.
A Method to Measure Aggressiveness of Plasmopara halstedii (Sunflower Downy Mildew)
Authors: Sakr Nachaat , Ducher Mireille , Tourvieille Jeanne , Walser Pascal , Vear Félicity , De Labrouhe Denis Tourvieille
Published: October 2008

For the first time, a method was used to measure aggressiveness of two Plasmopara halstedii races (100 and 710), the parasite causing sunflower downy mildew. Two sunflower lines showing different levels of quantitative resistance were used to measure two aggressiveness criteria: latent period and sporulation density. A strain of race 100 had a shorter latent period and greater sporulation density than a strain of race 710. The sunflower inbred line BT, rather susceptible in the field, presented a greater sporulation density and a shorter latent period than another inbred line FU, which shows greater resistance in the field. These results indicated that race 100 was more aggressive than race 710. The behaviour in the field of the two inbred lines was confirmed in the laboratory observations.
Mode of Action of the Antibacterial Compound Ar26 Produced by Agrobacterium vitis Strain E26 with Activity against A. tumefaciens, A. rhizogenes and A. vitis
Authors: Li Jin‐Yun , Wang Jian‐Hui , Wang Hui‐Min
Published: October 2008

The biological control bacterium Agrobacterium vitis strain E26 was previously shown to produce an antibacterial compound, Ar26. This compound was involved in the biocontrol process and inhibited grapevine crown gall‐causing A. vitis strains in vitro by an unknown mechanism. This work was undertaken to determine the antibacterial properties and mode of action of Ar26. In a well agar plate diffusion assay against 29 tumorigenic isolates of Agrobacterium spp., Ar26 displayed broad inhibitory activity against 27. All of the 10 A. vitis, 8 of 9 A. tumefaciens and 9 of 10 A. rhizogenes strains were sensitive to this compound. Agrobacterium vitis strains were more sensitive to Ar26 than A. tumefaciens or A. rhizogenes strains, with larger inhibition zones and lower minimal inhibitory concentration (MIC). Ar26 exhibited a bactericidal effect against A. vitis. This compound did not cause bacterial cell lysis, as determined by morphological observation with an electronic microscope. Also, no leakage of cytoplasmic materials from cells of A. vitis occurred after treatment with Ar26 at concentrations equivalent to the MIC. However, an inhibition of the incorporation of radiolabelled precursors into DNA, RNA and protein was observed after treatment with Ar26. Results obtained suggest that Ar26 inhibited DNA, RNA and protein syntheses in tumorigenic A. vitis.