bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Unique Arabinose 5-Phosphate Isomerase Found within a Genomic Island Associated with the Uropathogenicity of Escherichia coli CFT073
Authors: Mosberg Joshua A. , Yep Alejandra , Meredith Timothy C. , Smith Sara , Wang Pan-Fen , Holler Tod P. , Mobley Harry L. T. , Woodard Ronald W. 
Published: April 2011

ABSTRACT

Previous studies showed that deletion of genes c3405 to c3410 from PAI-
metV
, a genomic island from
Escherichia coli
CFT073, results in a strain that fails to compete with wild-type CFT073 after a transurethral cochallenge in mice and is deficient in the ability to independently colonize the mouse kidney. Our analysis of c3405 to c3410 suggests that these genes constitute an operon with a role in the internalization and utilization of an unknown carbohydrate. This operon is not found in
E. coli
K-12 but is present in a small number of pathogenic
E. coli
and
Shigella boydii
strains. One of the genes, c3406, encodes a protein with significant homology to the sugar isomerase domain of arabinose 5-phosphate isomerases but lacking the tandem cystathionine beta-synthase domains found in the other arabinose 5-phosphate isomerases of
E. coli
. We prepared recombinant c3406 protein, found it to possess arabinose 5-phosphate isomerase activity, and characterized this activity in detail. We also constructed a c3406 deletion mutant of
E. coli
CFT073 and demonstrated that this deletion mutant was still able to compete with wild-type CFT073 in a transurethral cochallenge in mice and could colonize the mouse kidney. These results demonstrate that the presence of c3406 is not essential for a pathogenic phenotype.
Interactions and Predicted Host Membrane Topology of the Enteropathogenic Escherichia coli Translocator Protein EspB
Authors: Luo Wensheng , Donnenberg Michael S. 
Published: April 2011

ABSTRACT

Type 3 secretion systems (T3SSs) are critical for the virulence of numerous deadly Gram-negative pathogens. T3SS translocator proteins are required for effector proteins to traverse the host cell membrane and perturb cell function. Translocator proteins include two hydrophobic proteins, represented in enteropathogenic
Escherichia coli
(EPEC) by EspB and EspD, which are thought to interact and form a pore in the host membrane. Here we adapted a sequence motif recognized by a host kinase to demonstrate that residues on the carboxyl-terminal side of the EspB transmembrane domain are localized to the host cell cytoplasm. Using functional internal polyhistidine tags, we confirm an interaction between EspD and EspB, and we demonstrate, for the first time, an interaction between EspD and the hydrophilic translocator protein EspA. Using a panel of
espB
insertion mutations, we describe two regions on either side of a putative transmembrane domain that are required for the binding of EspB to EspD. Finally, we demonstrate that EspB variants incapable of binding EspD fail to adopt the proper host cell membrane topology. These results provide new insights into interactions between translocator proteins critical for virulence.
Tobacco litter costs and public policy: a framework and methodology for considering the use of fees to offset abatement costs: Figure 1
Authors: Schneider John E , Peterson N Andrew , Kiss Noemi , Ebeid Omar , Doyle Alexis S 
Published: April 2011

ObjectivesGrowing concern over the costs, environmental impact and safety of tobacco product litter (TPL) has prompted states and cities to undertake a variety of policy initiatives, of which litter abatement fees are part. The present work describes a framework and methodology for calculating TPL costs and abatement fees.MethodsAbatement is associated with four categories of costs: (1) mechanical and manual abatement from streets, sidewalks and public places, (2) mechanical and manual abatement from storm water and sewer treatment systems, (3) the costs associated with harm to the ecosystem and harm to industries dependent on clean and healthy ecosystems, and (4) the costs associated with direct harm to human health. The experiences of the City of San Francisco's recently proposed tobacco litter abatement fee serve as a case study.ResultsCity and municipal TPL costs are incurred through manual and mechanical clean-up of surfaces and catchment areas. According to some studies, public litter abatement costs to US cities range from US$3 million to US$16 million. TPL typically comprises between 22% and 36% of all visible litter, implying that total public TPL direct abatement costs range from about US$0.5 million to US$6 million for a city the size of San Francisco. The costs of mitigating the negative externalities of TPL in a city the size of San Francisco can be offset by implementing a fee of approximately US$0.20 per pack.ConclusionsTobacco litter abatement costs to cities can be substantial, even when the costs of potential environmental pollution and tourism effects are excluded. One public policy option to address tobacco litter is levying of fees on cigarettes sold. The methodology described here for calculating TPL costs and abatement fees may be useful to state and local authorities who are considering adoption of this policy initiative.
Menthol sensory qualities and smoking topography: a review of tobacco industry documents
Authors: Yerger Valerie B , McCandless Phyra M 
Published: April 2011

ObjectiveTo determine what the tobacco industry knew about the potential effects of menthol on smoking topography—how a person smokes a cigarette.MethodsA snowball strategy was used to systematically search the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) between 1 June 2010 and 9 August 2010. We qualitatively analysed a final collection of 252 documents related to menthol and smoking topography.ResultsThe tobacco industry knew that menthol has cooling, anaesthetic and analgesic properties that moderate the harshness and irritation of tobacco. Owing to its physiological effects, menthol contributes to the sensory qualities of the smoke and affects smoking topography and cigarette preference.ConclusionOur review of industry studies suggests that the amount of menthol in a cigarette is associated with how the cigarette is smoked and how satisfying it is to the smoker. If menthol in cigarettes was banned, as the US Food and Drug Administration (FDA) is currently considering, new/experimental smokers might choose not to smoke rather than experience the harshness of tobacco smoke and the irritating qualities of nicotine. Similarly, established menthol smokers might choose to quit if faced with an unpleasant smoking alternative.
Menthol: putting the pieces together
Authors: Lee Youn Ok , Glantz Stanton A 
Published: April 2011

ObjectiveTo integrate information on cigarette companies' understanding and use of menthol as summarised in published research based on previously internal tobacco industry documents with results from large population-based surveys of tobacco use and other independent sources.Data sourcesPapers published in this supplement ofTobacco Control, together with papers identified using PubMed searches.ResultsTobacco companies shaped consumer perceptions of menthol cigarettes. Menthol is not just a flavouring agent. Cigarette companies use menthol's ability to mask irritation and provide sensory effects to make menthol cigarettes appeal to youth and health-concerned smokers, in part because menthol makes low-tar cigarettes more palatable. Consistent with targeted marketing, youths, women and African Americans disproportionately smoke menthols. There appear to be complex interactions with addictive effects of nicotine. The ubiquitous addition of menthol by tobacco companies to over 90% of all tobacco products, whether labelled ‘menthol’ or not, demonstrates that menthol is not simply a flavour or brand. Menthol imparts sensory characteristics to cigarettes and has a complex interaction with nicotine that affects smoking behaviour whether it is perceived or not, or whether cigarettes containing menthol are marketed as ‘menthol’ or not. Adding menthol increases fine particles in cigarette smoke, which have immediate adverse effects on the risk of heart attack.ConclusionInformation from industry documents, confirmed by independent scientific literature, consistently demonstrates that menthol increases population harm from smoking by increasing initiation and reducing cessation in some groups. Menthol facilitates and increases smoking, which causes disease and death.
CNGI-CERNET2
Authors: Wu Jianping , Wang Jessie Hui , Yang Jiahai 
Published: April 2011

Research and promotion of next generation Internet have drawn attention of researchers in many countries. In USA, FIND initiative takes a clean-slate approach. In EU, EIFFEL think tank concludes that both clean slate and evolutionary approach are needed. While in China, researchers and the country are enthusiastic on the promotion and immediate deployment of IPv6 due to the imminent problem of IPv4 address exhaustion.
Since 2003, China launched a strategic programme called China Next Generation Internet (CNGI). China is expecting that Chinese industry is better positioned on future Internet technologies and services than it was for the first generation. Under the support of CNGI grant, China Education and Research Network (CERNET) started to build an IPv6-only network, i.e. CNGI-CERNET2. Currently it provides IPv6 access service for students and staff in many Chinese universities. In this article, we will introduce the CNGI programme, the architecture of CNGI-CERNET2, and some aspects of CNGI-CERNET2's deployment and operation, such as transition, security, charging and roaming service etc.
IP geolocation databases
Authors: Poese Ingmar , Uhlig Steve , Kaafar Mohamed Ali , Donnet Benoit , Gueye Bamba 
Published: April 2011

The most widely used technique for IP geolocation consists in building a database to keep the mapping between IP blocks and a geographic location. Several databases are available and are frequently used by many services and web sites in the Internet. Contrary to widespread belief, geolocation databases are far from being as reliable as they claim. In this paper, we conduct a comparison of several current geolocation databases -both commercial and free- to have an insight of the limitations in their usability.
First, the vast majority of entries in the databases refer only to a few popular countries (e.g., U.S.). This creates an imbalance in the representation of countries across the IP blocks of the databases. Second, these entries do not reflect the original allocation of IP blocks, nor BGP announcements. In addition, we quantify the accuracy of geolocation databases on a large European ISP based on ground truth information. This is the first study using a ground truth showing that the overly fine granularity of database entries makes their accuracy worse, not better. Geolocation databases can claim country-level accuracy, but certainly not city-level.
A Genome-Wide Search for Promoters That Respond to Increased MYCN Reveals Both New Oncogenic and Tumor Suppressor MicroRNAs Associated with Aggressive Neuroblastoma
Authors: Shohet Jason M. , Ghosh Rajib , Coarfa Cristian , Ludwig Andrew , Benham Ashley L. , Chen Zaowen , Patterson Danielle M. , Barbieri Eveline , Mestdagh Pieter , Sikorski Denae N. , Milosavljevic Aleksandar , Kim Eugene S. , Gunaratne Preethi H. 
Published: April 2011

Abstract
MYCN is a major driver of neuroblastoma tumorigenesis and MYCN amplification is the worst prognostic indicator of aggressive NB. To identify potentially therapeutic tumor suppressor microRNAs for aggressive NB, we utilized a conditional MYCN system to simulate MYCN-amplified and nonamplified tumor types and performed a genome-wide search for MYCN target microRNA promoters differentially repressed under high MYCN conditions. We identified 20 gene promoters hosting 30 microRNAs that were directly bound and differentially regulated by MYCN. Eleven of these genes showed significant clinical correlations for neuroblastoma with 4 genes linked with better survival and 7 genes linked with poor survival. Surprisingly, expression analysis of host genes and microRNAs demonstrated that 8 of 11 pairs were repressed by high levels of MYCN regardless of the clinical correlation of the host gene. We therefore predicted these intronic microRNAs would be tumor suppressors. In fact, detailed gain of function studies for two miRs, miR-591 and miR-558, confirmed potent tumor suppressive effects for miR-591 in orthotopic neuroblastoma xenografts. However, miR-558 markedly increased colony formation, proliferation, and tumor growth in vivo. Our data reveal host-gene independent functions of MYCN-target microRNAs and demonstrate that MYCN represses both tumor suppressive and proproliferative microRNAs. Cancer Res; 71(11); 3841–51. ©2011 AACR.
The Id3/E47 Axis Mediates Cell-Cycle Control in Human Pancreatic Ducts and Adenocarcinoma
Authors: Lee Seung-Hee , Hao Ergeng , Kiselyuk Alice , Shapiro James , Shields David J. , Lowy Andrew , Levine Fred , Itkin-Ansari Pamela 
Published: April 2011

Abstract
Pancreatic ductal adenocarcinoma (PDA) has a 5-year survival rate of less than 5%, and therapeutic advances have been hampered by gaps in our understanding of cell-cycle control in the adult pancreas. Previously, we reported that basic Helix-Loop-Helix (bHLH) transcription factors regulate cell fate specification in the pancreas. In the present study, we found that a repressor of bHLH activity, Id3, was profoundly upregulated in ductal cells in murine models of pancreatitis and pancreatic intraepithelial neoplasia (PanIN). Id3 was also pervasively expressed in neoplastic lesions in human PDA in situ. We hypothesized that an imbalance in bHLH versus Id activity controlled cell growth in PDA. Consistent with this model, cell-cycle progression in PDA cells was impeded by siRNA-mediated depletion of Id3 or overexpression of the bHLH protein E47. The precursors of human PDA are normally quiescent duct cells which do not proliferate in response to high serum or growth factors. The finding that Id3 was expressed in pancreatitis, as well as PDA, suggested that Id3 might induce cell-cycle entry in ducts. To test this hypothesis, primary human pancreatic duct cells were transduced with an adenovirus-expressing Id3. Remarkably, Id3 expression alone was sufficient to trigger efficient cell-cycle entry, as manifested by expression of the proliferation markers Ki67, phospho-cyclin E, and phospho-histone H3. Collectively, the data establish dysregulation of the Id/bHLH axis as an early and sustained feature of ductal pathogenesis and mark this axis as a potential therapeutic target for intervention in pancreatitis and PDA. Mol Cancer Res; 9(6); 782–90. ©2011 AACR.
Long-Term Prognosis of Patients With Kawasaki Disease Complicated by Giant Coronary Aneurysms
Authors: Suda Kenji , Iemura Motofumi , Nishiono Hiroshi , Teramachi Yozo , Koteda Yusuke , Kishimoto Shintaro , Kudo Yoshiyuki , Itoh Shinichi , Ishii Haruka , Ueno Takafumi , Tashiro Tadashi , Nobuyoshi Masakiyo , Kato Hirohisa , Matsuishi Toyojiro 
Published: April 2011

Background—
Some patients with Kawasaki disease develop giant coronary aneurysms and coronary stenosis, leading to ischemic heart disease. The aim of this study was to determine the long-term prognosis of patients with Kawasaki disease with giant aneurysms.

Methods and Results—
From our institutional database, 76 patients (57 men and 19 women) who developed giant aneurysms after January 1, 1972, were identified. Information on patient demographics, catheter and surgical interventions, and most recent status was collected from medical charts and patients' contacts. From these data, we calculated the survival rate and cumulative coronary intervention rate. The average age at onset was 2.9±2.9 years, and the median observational period was 19 years. During this period, 7 patients died and 1 patient underwent a heart transplantation, resulting in 95%, 88%, and 88% survival rates at 10, 20, and 30 years after the onset of KD, respectively. On the other hand, catheter and surgical coronary interventions (median, 1 intervention; range, 1 to 7 interventions) were performed to alleviate coronary ischemia in 46 patients (61%) at 1 month to 21 years (mode at 1 month) after onset, resulting in 28%, 43%, and 59% cumulative coronary intervention rates at 5, 15, and 25 years after onset, respectively.

Conclusions—
The long-term survival of patients with Kawasaki disease complicated by giant coronary aneurysms is moderately good with multiple catheter and surgical interventions. Further research should focus on the prevention of coronary vascular remodeling and on the indications for and effectiveness of percutaneous and surgical coronary interventions.
Novel Antiplatelet Drug Revacept (Dimeric Glycoprotein VI-Fc) Specifically and Efficiently Inhibited Collagen-Induced Platelet Aggregation Without Affecting General Hemostasis in Humans
Authors: Ungerer Martin , Rosport Kai , Bültmann Andreas , Piechatzek Richard , Uhland Kerstin , Schlieper Peter , Gawaz Meinrad , Münch Götz 
Published: April 2011

Background—
Blocking of glycoprotein VI–dependent pathways by interfering in vascular collagen sites is commonly seen as an attractive target for an antiplatelet therapy of acute atherosclerotic diseases such as myocardial infarction or stroke. Revacept (soluble dimeric glycoprotein VI-Fc fusion protein) has been shown to reduce platelet adhesion by blocking vascular collagen in plaques or erosion and to be safe in preclinical studies. A dose-escalating clinical phase I study was performed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of Revacept in humans.

Methods and Results—
In a first-in-humans study, 30 healthy men received a single intravenous administration of 10, 20, 40, 80, or 160 mg Revacept. The serum concentration–time courses of each dosage of Revacept showed a narrow variation and a concentration and time dependence. Revacept did not significantly affect the bleeding time. Collagen-induced platelet aggregation was dose-dependently inhibited up to 48 hours at lower doses and for 7 days after higher dose levels. In contrast, ADP- or thrombin receptor activating peptide–dependent platelet aggregation remained unaltered. There were no relevant drug-related adverse events or drug-related changes in laboratory parameters (biochemistry, hematology, and coagulation parameters). There were no drug-related changes in blood pressure, pulse rate, or ECG parameters (including 24-hour Holter monitoring). No anti-Revacept antibodies were detected.

Conclusion—
This phase I study demonstrated that Revacept is a safe and well-tolerated new antiplatelet compound with a clear dose-dependent pharmacokinetic profile with specific, dose-related inhibition of platelet aggregation despite completely unaltered general hemostasis.

Clinical Trial Registration—

URL:
www.clinicaltrials.gov
. Unique identifier: NCT 01042964. URL: eudract.ema.europa.eu. Identifier: 2005–004656-12.
Transmural Heterogeneity and Remodeling of Ventricular Excitation-Contraction Coupling in Human Heart Failure
Authors: Lou Qing , Fedorov Vadim V. , Glukhov Alexey V. , Moazami Nader , Fast Vladimir G. , Efimov Igor R. 
Published: April 2011

Background—
Excitation-contraction (EC) coupling is altered in end-stage heart failure. However, spatial heterogeneity of this remodeling has not been established at the tissue level in failing human heart. The objective of this article was to study functional remodeling of excitation-contraction coupling and calcium handling in failing and nonfailing human hearts.

Methods and Results—

We simultaneously optically mapped action potentials and calcium transients in coronary perfused left ventricular wedge preparations from nonfailing (n=6) and failing (n=5) human hearts. Our major findings are the following. First, calcium transient duration minus action potential duration was longer at subendocardium in failing compared with nonfailing hearts during bradycardia (40 bpm). Second, the transmural gradient of calcium transient duration was significantly smaller in failing hearts compared with nonfailing hearts at fast pacing rates (100 bpm). Third, calcium transient in failing hearts had a flattened plateau at the midmyocardium and exhibited a 2-component slow rise at the subendocardium in 3 failing hearts. Fourth, calcium transient relaxation was slower at the subendocardium than at the subepicardium in both groups. Protein expression of sarcoplasmic reticulum Ca
2+
-ATPase 2a was lower at the subendocardium than the subepicardium in both nonfailing and failing hearts. Sarcoplasmic reticulum Ca
2+
-ATPase 2a protein expression at subendocardium was lower in hearts with ischemic cardiomyopathy compared with those with nonischemic cardiomyopathy.

Conclusions—
For the first time, we present direct experimental evidence of transmural heterogeneity of excitation-contraction coupling and calcium handling in human hearts. End-stage heart failure is associated with the heterogeneous remodeling of excitation-contraction coupling and calcium handling.
On the Growth and Decay of the Subtropical Dipole Mode in the South Atlantic
Authors: Morioka Yushi , Tozuka Tomoki , Yamagata Toshio 
Published: April 2011

Abstract
Using observational data and outputs from an ocean general circulation model, the growth and decay of the South Atlantic subtropical dipole (SASD) are studied. The SASD is the most dominant mode of interannual variability in the South Atlantic Ocean, and its sea surface temperature (SST) anomaly shows a dipole pattern that is oriented in the northeast–southwest direction. The positive (negative) pole develops because the warming of the mixed layer by the contribution from the climatological shortwave radiation is enhanced (suppressed) when the mixed layer is thinner (thicker) than normal. The mixed layer depth anomaly over the positive (negative) pole is due to the suppressed (enhanced) latent heat flux loss associated with the southward migration and strengthening of the subtropical high. During the decay phase, since the temperature difference between the mixed layer and the entrained water becomes anomalously large (small) as a result of the positive (negative) mixed layer temperature anomaly, the cooling of the mixed layer by the entrainment is enhanced (reduced). In addition, the cooling of the mixed layer by the contribution from the climatological latent heat flux is enhanced (suppressed) by the same thinner (thicker) mixed layer. This paper demonstrates the importance of taking into account the interannual variations of the mixed layer depth in discussing the growth and decay of SST anomalies associated with the SASD.