bluuebunny/crossref_metadata_2025_split 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
\[

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

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.
Causes and consequences of life-history variation in North American stocks of Pacific cod
Authors: Ormseth Olav A. , Norcross Brenda L. 
Published: October 2008

AbstractOrmseth, 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

Abstract
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.
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

AbstractIn 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

AbstractThe 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

AbstractComparative 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

SummaryAngiogenesis, 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

SummaryThe 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

SummaryValproic 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.