bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFICIENCY OF MAJOR PORTS UNDER LOGISTICS RISK IN NORTHEAST ASIA
Authors: CHOI YONGROK 
Published: February 2011

In this paper, we present an empirical study on the efficiency of the major ports in Northeast Asia. To become the global hub in a newly emerging Northeast Asian logistics network, the efficiency of the ports and their success factors are important for sustainable development. Thus, the comparison of port efficiency may shed light on this rapidly changing and thus very risky logistics network in Asia. The paper analyzes empirical results on the efficiencies of major ports by applying the generally acceptable methodology of data envelope analysis (DEA) and its variant models. In our empirical results, most of ports showed the stronger position in pure efficiency, but weak position in scale efficiency. It implies that the promotion policies to become a hub under the rapidly changing logistics network should be based on the operational innovation such as the effective governance by the anchor companies or strategic alliances with global partners. So the paper strongly requests that the government should focus on the governance, instead of the infrastructure or facility to avoid the operational risks under the rapidly changing logistics network. Therefore, all the seaports should have sustainable development strategies that adapt to technological change. This paper concludes that the scale- or supply-oriented policies should be changed to emphasize more the governance of port operations. Also, the paper concludes that investment in infrastructure does not improve efficiency; rather self-created logistics demand and strategic alliances, such as anchor companies, do improve the efficiency as demonstrated by the Tobit model.
Discovery of DNA Repair Inhibitors by Combinatorial Library Profiling
Authors: Moeller Benjamin J. , Sidman Richard L. , Pasqualini Renata , Arap Wadih 
Published: February 2011

Abstract
Small molecule inhibitors of DNA repair are emerging as potent and selective anticancer therapies, but the sheer magnitude of the protein networks involved in DNA repair processes poses obstacles to discovery of effective candidate drugs. To address this challenge, we used a subtractive combinatorial selection approach to identify a panel of peptide ligands that bind DNA repair complexes. Supporting the concept that these ligands have therapeutic potential, we show that one selected peptide specifically binds and noncompetitively inactivates DNA-PKcs, a protein kinase critical in double-strand DNA break repair. In doing so, this ligand sensitizes BRCA-deficient tumor cells to genotoxic therapy. Our findings establish a platform for large-scale parallel screening for ligand-directed DNA repair inhibitors, with immediate applicability to cancer therapy. Cancer Res; 71(5); 1816–24. ©2011 AACR.
Peroxiredoxin 1 Controls Prostate Cancer Growth through Toll-Like Receptor 4–Dependent Regulation of Tumor Vasculature
Authors: Riddell Jonah R. , Bshara Wiam , Moser Michael T. , Spernyak Joseph A. , Foster Barbara A. , Gollnick Sandra O. 
Published: February 2011

Abstract
In recent years a number of studies have implicated chronic inflammation in prostate carcinogenesis. However, mitigating factors of inflammation in the prostate are virtually unknown. Toll-like receptor 4 (TLR4) activity is associated with inflammation and is correlated with progression risk in prostate cancer (CaP). TLR4 ligands include bacterial cell wall proteins, danger signaling proteins, and intracellular proteins such as heat shock proteins and peroxiredoxin 1 (Prx1). Here we show that Prx1 is overexpressed in human CaP specimens and that it regulates prostate tumor growth through TLR4-dependent regulation of prostate tumor vasculature. Inhibiting Prx1 expression in prostate tumor cells reduced tumor vascular formation and function. Furthermore, Prx1 inhibition reduced levels of angiogenic proteins such as VEGF within the tumor microenvironment. Lastly, Prx1-stimulated endothelial cell proliferation, migration, and differentiation in a TLR4- and VEGF-dependent manner. Taken together, these results implicate Prx1 as a tumor-derived inducer of inflammation, providing a mechanistic link between inflammation and TLR4 in prostate carcinogenesis. Our findings implicate Prx1 as a novel therapeutic target for CaP. Cancer Res; 71(5); 1637–46. ©2011 AACR.
IL6-STAT3-HIF Signaling and Therapeutic Response to the Angiogenesis Inhibitor Sunitinib in Ovarian Clear Cell Cancer
Authors: Anglesio Michael S. , George Joshy , Kulbe Hagen , Friedlander Michael , Rischin Danny , Lemech Charlotte , Power Jeremy , Coward Jermaine , Cowin Prue A. , House Colin M. , Chakravarty Probir , Gorringe Kylie L. , Campbell Ian G. ,   Australian Ovarian Cancer Study Group, Okamoto Aikou , Birrer Michael J. , Huntsman David G. , de Fazio Anna , Kalloger Steve E. , Balkwill Frances , Gilks C. Blake , Bowtell David D. 
Published: February 2011

AbstractPurpose: Ovarian clear cell adenocarcinoma (OCCA) is an uncommon histotype that is generally refractory to platinum-based chemotherapy. We analyze here the most comprehensive gene expression and copy number data sets, to date, to identify potential therapeutic targets of OCCA.Experimental Design: Gene expression and DNA copy number were carried out using primary human OCCA tumor samples, and findings were confirmed by immunohistochemistry on tissue microarrays. Circulating interleukin (IL) 6 levels were measured in serum from patients with OCCA or high-grade serous cancers and related to progression-free and overall survival. Two patients were treated with sunitinib, and their therapeutic responses were measured clinically and by positron emission tomography.Results: We find specific overexpression of the IL6-STAT3-HIF (interleukin 6-signal transducer and activator of transcription 3-hypoxia induced factor) pathway in OCCA tumors compared with high-grade serous cancers. Expression of PTHLH and high levels of circulating IL6 in OCCA patients may explain the frequent occurrence of hypercalcemia of malignancy and thromboembolic events in OCCA. We describe amplification of several receptor tyrosine kinases, most notably MET, suggesting other potential therapeutic targets. We report sustained clinical and functional imaging responses in two OCCA patients with chemotherapy-resistant disease who were treated with sunitinib, thus showing significant parallels with renal clear cell cancer.Conclusions: Our findings highlight important therapeutic targets in OCCA, suggest that more extensive clinical trials with sunitinib in OCCA are warranted, and provide significant impetus to the growing realization that OCCA is molecularly and clinically distinct to other forms of ovarian cancer. Clin Cancer Res; 17(8); 2538–48. ©2011 AACR.
Autophagy-Dependent Regulation of the DNA Damage Response Protein Ribonucleotide Reductase 1
Authors: Dyavaiah Madhu , Rooney John P. , Chittur Sridar V. , Lin Qishan , Begley Thomas J. 
Published: February 2011

Abstract
Protein synthesis and degradation are posttranscriptional pathways used by cells to regulate protein levels. We have developed a systems biology approach to identify targets of posttranscriptional regulation and we have employed this system in Saccharomyces cerevisiae to study the DNA damage response. We present evidence that 50% to 75% of the transcripts induced by alkylation damage are regulated posttranscriptionally. Significantly, we demonstrate that two transcriptionally-induced DNA damage response genes, RNR1 and RNR4, fail to show soluble protein level increases after DNA damage. To determine one of the associated mechanisms of posttranscriptional regulation, we tracked ribonucleotide reductase 1 (Rnr1) protein levels during the DNA damage response. We show that RNR1 is actively translated after damage and that a large fraction of the corresponding Rnr1 protein is packaged into a membrane-bound structure and transported to the vacuole for degradation, with these last two steps dependent on autophagy proteins. We found that inhibition of target of rapamycin (TOR) signaling and subsequent induction of autophagy promoted an increase in targeting of Rnr1 to the vacuole and a decrease in soluble Rnr1 protein levels. In addition, we demonstrate that defects in autophagy result in an increase in soluble Rnr1 protein levels and a DNA damage phenotype. Our results highlight roles for autophagy and TOR signaling in regulating a specific protein and demonstrate the importance of these pathways in optimizing the DNA damage response. Mol Cancer Res; 9(4); 462–75. ©2011 AACR.
Dominant-Negative Features of Mutant TP53 in Germline Carriers Have Limited Impact on Cancer Outcomes
Authors: Monti Paola , Perfumo Chiara , Bisio Alessandra , Ciribilli Yari , Menichini Paola , Russo Debora , Umbach David M. , Resnick Michael A. , Inga Alberto , Fronza Gilberto 
Published: February 2011

Abstract
Germline TP53 mutations result in cancer proneness syndromes known as Li-Fraumeni, Li-Fraumeni-like, and nonsyndromic predisposition with or without family history. To explore genotype/phenotype associations, we previously adopted a functional classification of all germline TP53 mutant alleles based on transactivation. Severe deficiency (SD) alleles were associated with more severe cancer proneness syndromes, and a larger number of tumors, compared with partial deficiency (PD) alleles. Because mutant p53 can exert dominant-negative (DN) effects, we addressed the relationship between DN and clinical manifestations. We reasoned that DN effects might be stronger in familial cancer cases associated with germline TP53 mutations, where mutant alleles coexist with the wild-type allele since conception. We examined 104 p53 mutant alleles with single amino acid substitutions described in the IARC germline database for (i) transactivation capability and (ii) capacity to reduce the activity of the wild-type allele (i.e., DN effect) using a quantitative yeast-based assay. The functional classifications of p53 alleles were then related to clinical variables. We confirmed that a classification based on transactivation alone can identify familial cancer cases with more severe clinical features. Classification based on DN effects allowed us to highlight similar associations but did not reveal distinct clinical subclasses of SD alleles, except for a correlation with tumor tissue prevalence. We conclude that in carriers of germline TP53 mutations transactivation-based classification of TP53 alleles appears more important for genotype/phenotype correlations than DN effects and that haplo-insufficiency of the TP53 gene is an important factor in cancer proneness in humans. Mol Cancer Res; 9(3); 271–9. ©2011 AACR.
Reply to Bhatt and Pancheva's “Late Merger of Degree Clauses”: The Irrelevance of (Non)conservativity
Authors: Grosu Alexander , Horvath Julia 
Published: February 2011

According to Bhatt and Pancheva (2004), two effects they attribute to degree constructions (obligatory extraposition effects and scope rigidity effects determined by the superficial position of degree phrases/clauses) can be given a unified analysis in terms of an extension of Fox and Nissenbaum's (1999) analysis of extraposition in conjunction with the nonconservativity of (certain) degree words. We show that, under full preservation of Bhatt and Pancheva's theoretical assumptions, their account faces at least three problems: (a) one of the phenomena they propose to unify, the one involving scope effects, does not exist; (b) (non)conservativity is irrelevant to obligatory extraposition effects; and (c) contrary to their tacit assumption, Trace Conversion is at most an optional procedure for DegP chains. We propose an alternative, nonsemantic treatment of obligatory extraposition effects, which subsumes them under an independently needed adjacency constraint on prehead modifiers. Furthermore, we note that the facts brought up here and in Bhatt and Pancheva 2004 call into question the quantificational approach to degree constructions.
Nonstationarity in Multifactor Models of Discrete Jump Processes, Memory, and Application to Cloud Modeling
Authors: Horenko Illia 
Published: February 2011

Abstract
Because of the mathematical and numerical limitations, standard statistical methods known from the literature are not applicable to inferring jump processes under exogenous influence. Such processes can be considered, for example, in the atmosphere (transitions between different cloud types) and in the ocean (phase transitions between water and ice). Reasons for these intrinsic limitations of standard methods are investigated and a method for the inference of discrete microscopic jump models based on macroscopic ensemble observations is presented. It significantly extends the recently developed methods of nonstationary Markov model parameterization (which are constrained to a single exogenous factor and to direct individual observations of the jump process realizations). The main advantage of the new method is the possibility of inference from indirect ensemble observations with multiple exogenous factors. Moreover, this method allows for a new possibility to test whether the available time series is best described via stationary or nonstationary and Markovian (with memory) or independent (without memory) processes. It also allows estimation of the relative significance of the exogenous factors and their impact on the jump probabilities. The new framework provides a unified toolkit for data analysis of jump processes with the same level of detail now possible for standard continuous state space tools. The resulting numerical algorithm is applied to analysis of the total relative cloud cover data in the midlatitudes and in the tropics under the influence of some meteorologically relevant local and global exogenous factors.
Pushing the Envelope for Cultural Appropriateness
Authors: Davis Rachel E. , Peterson Karen E. , Rothschild Steven K. , Resnicow Ken 
Published: February 2011

Purpose This study explores the potential utility of a culturally tailored diabetes management intervention approach by testing associations between acculturation and diabetes-related beliefs among Mexican-American adults with type 2 diabetes. Methods Data from 288 Mexican-American adults with type 2 diabetes were obtained via a bilingual, telephone-administered survey. Participants were drawn from a stratified, random sample designed to obtain maximum variability in acculturation. The survey assessed diabetes-related beliefs, intervention preferences, and the following three acculturation constructs from the Hazuda acculturation and assimilation scales: Spanish use, value for preserving Mexican culture, and interaction with Mexican Americans. Results Only one outcome—preference for a program for Mexican Americans—was associated with all three acculturation variables. Spanish use was positively associated with belief in susto as a cause of diabetes, preference for expert-driven health guidance, and involvement of others in taking care of diabetes. Value for preserving Mexican culture was related to a more holistic view of health, as evidenced by an increased likelihood of consulting a curandero, use of prayer, and interest in a diabetes program with religious content. Value for cultural preservation was also related to higher suspicion of free diabetes programs. Interaction with Mexican Americans was associated with a belief that insulin causes blindness. Conclusion Findings from this study suggest distinct relationships between acculturation constructs and diabetes-related beliefs and preferences, thus arguing against the use of a single acculturation construct to determine diabetes intervention design. Cultural tailoring may enhance the cultural appropriateness and ultimate effectiveness of diabetes interventions for Mexican American adults.
Visual-cognitive processing deficits in pediatric multiple sclerosis
Authors: Smerbeck AM , Parrish J , Serafin D , Yeh EA , Weinstock-Guttman B , Hoogs M , Krupp LB , Benedict RHB 
Published: February 2011

Background: Children with multiple sclerosis (MS) can suffer significant cognitive deficits. This study investigates the sensitivity and validity in pediatric MS of two visual processing tests borrowed from the adult literature, the Brief Visuospatial Memory Test-Revised (BVMTR) and the Symbol Digit Modalities Test (SDMT). Objective: To test the hypothesis that visual processing is disproportionately impacted in pediatric MS by comparing performance with that of healthy controls on the BVMTR and SDMT. Methods: We studied 88 participants (43 MS, 45 controls) using a neuropsychological assessment battery including measures of intelligence, language, visual memory, and processing speed. Patients and demographically matched controls were compared to determine which tests are most sensitive in pediatric MS. Results: Statistically significant differences were found between the MS and control groups on BVMTR Total Learning ( t (84) = 4.04, p < 0.001, d = 0.87), BVMTR Delayed Recall ( t (84) = 4.45, p < 0.001, d = 0.96), and SDMT ( t (38) = 2.19, p = 0.035, d = 0.69). No significant differences were found between groups on confrontation naming or general intellectual ability. Validity coefficients exploring correlation between BVMTR, SDMT, and disease characteristics were consistent with the adult literature. Conclusions: This study found that BVMTR and SDMT may be useful in assessing children and adolescents with MS.
Risk of MS is not associated with exposure to crude oil, but increases with low level of education
Authors: Riise Trond , Kirkeleit Jorunn , Harald Aarseth Jan , Farbu Elisabeth , Midgard Rune , Mygland Åse , Eikeland Randi , Jørgen Mørland Tore , Telstad Wenche , Tore Førland Per , Kjell-Morten Myhr  
Published: February 2011

Background: Offshore workers in the Norwegian upstream petroleum industry are exposed to a number of chemicals such as organic solvents, mineral oils and other hydrocarbons, possibly contributing to an increased risk of multiple sclerosis (MS). Objective: To estimate the risk of MS in this population compared with the general working population in Norway, adjusting for education. Methods: Using the Norwegian Registry of Employers and Employees we included all 27,900 offshore workers registered from 1981 to 2003 and 366,805 referents from the general working population matched by gender, age and community of residence. The cohort was linked to the Norwegian MS Registry and the Norwegian Education Registry. Results: There was no increased risk of MS among the offshore workers. We found a marked and linear inverse relationship between level of education and the risk of MS in the total study population, with a rate ratio of 0.48 (95% CI, 0.53 to 0.88) for workers with a graduate degree compared to workers with elementary school only. Conclusions: These findings do not support a major aetiological role of petroleum-based products, but rather point to smoking and other lifestyle factors related to the level of education as being important for the risk of MS.
Shifting priorities in multimorbidity: a longitudinal qualitative study of patient’s prioritization of multiple conditions
Authors: Morris Rebecca L , Sanders Caroline , Kennedy Anne P , Rogers Anne 
Published: February 2011

Objective: To examine what influences self-management priorities for individuals with multiple long-term conditions and how this changes over time. Methods: A longitudinal qualitative study using semi-structured interviews completed with 21 participants with more than one chronic condition. Results: The study demonstrates the impact of multiple conditions on many aspects of people’s illness management. Narratives illuminated how individual’s condition priorities changed at pivotal points and altered their engagement with self-management practices. This is influenced by contact with health professionals and how people framed illness and lifestyle changes. Medication management was a central point where individuals took control of their conditions. Additional conditions were more readily accommodated if people established a cognitive link between existing management practices. Thus, multiple conditions were not inevitably experienced as an increasing burden but subject to considerable flux and change. Discussion: Prioritizing one condition over another at a particular time together with a transfer and amalgamation of practices appears to facilitate accommodation of multiple conditions and ease the burden of everyday management. These findings have implications for how we understand the variable nature of multimorbidity experience and management for patients. Clinicians might usefully engage with patients’ understanding to reduce complexity, and enhance engagement of condition management.
The replication rate of human hematopoietic stem cells in vivo
Authors: Catlin Sandra N. , Busque Lambert , Gale Rosemary E. , Guttorp Peter , Abkowitz Janis L. 
Published: February 2011

AbstractHematopoietic stem cells (HSCs) replicate (self-renew) to create 2 daughter cells with capabilities equivalent to their parent, as well as differentiate, and thus can both maintain and restore blood cell production. Cell labeling with division-sensitive markers and competitive transplantation studies have been used to estimate the replication rate of murine HSCs in vivo. However, these methods are not feasible in humans and surrogate assays are required. In this report, we analyze the changing ratio with age of maternal/paternal X-chromosome phenotypes in blood cells from females and infer that human HSCs replicate on average once every 40 weeks (range, 25-50 weeks). We then confirm this estimate with 2 independent approaches, use the estimate to simulate human hematopoiesis, and show that the simulations accurately reproduce marrow transplantation data. Our simulations also provide evidence that the number of human HSCs increases from birth until adolescence and then plateaus, and that the ratio of contributing to quiescent HSCs in humans significantly differs from mouse. In addition, they suggest that human marrow failure, such as the marrow failure that occurs after umbilical cord blood transplantation and with aplastic anemia, results from insufficient numbers of early progenitor cells, and not the absence of HSCs.
Genome-wide analysis of target genes regulated by HoxB4 in hematopoietic stem and progenitor cells developing from embryonic stem cells
Authors: Oshima Motohiko , Endoh Mitsuhiro , Endo Takaho A. , Toyoda Tetsuro , Nakajima-Takagi Yaeko , Sugiyama Fumihiro , Koseki Haruhiko , Kyba Michael , Iwama Atsushi , Osawa Mitsujiro 
Published: February 2011

AbstractForced expression of the transcription factor HoxB4 has been shown to enhance the self-renewal capacity of mouse bone marrow hematopoietic stem cells (HSCs) and confer a long-term repopulating capacity to yolk sac and embryonic stem (ES) cell–derived hematopoietic precursors. The fact that ES cell–derived precursors do not repopulate bone marrow without HoxB4 underscores an important role for HoxB4 in the maturation of ES-derived hematopoietic precursors into long-term repopulating HSCs. However, the precise molecular mechanism underlying this process is barely understood. In this study, we performed a genome-wide analysis of HoxB4 using ES cell–derived hematopoietic stem/progenitor cells. The results revealed many of the genes essential for HSC development to be direct targets of HoxB4, such as Runx1, Scl/Tal1, Gata2, and Gfi1. The expression profiling also showed that HoxB4 indirectly affects the expression of several important genes, such as Lmo2, Erg, Meis1, Pbx1, Nov, AhR, and Hemgn. HoxB4 tended to activate the transcription, but the down-regulation of a significant portion of direct targets suggested its function to be context-dependent. These findings indicate that HoxB4 reprograms a set of key regulator genes to facilitate the maturation of developing HSCs into repopulating cells. Our list of HoxB4 targets also provides novel candidate regulators for HSCs.