bluuebunny/crossref_metadata_2025 huggingface dataset:
Campylobacter jejuni Lipooligosaccharides Modulate Dendritic Cell-Mediated T Cell Polarization in a Sialic Acid Linkage-Dependent Manner
Authors: Bax Marieke , Kuijf Mark L. , Heikema Astrid P. , van Rijs Wouter , Bruijns Sven C. M. , García-Vallejo Juan J. , Crocker Paul R. , Jacobs Bart C. , van Vliet Sandra J. , van Kooyk Yvette
Published: April 2011

Carbohydrate mimicry betweenCampylobacter jejunilipooligosaccharides (LOS) and host neural gangliosides plays a crucial role in the pathogenesis of Guillain-Barré syndrome (GBS).Campylobacter jejuniLOS may mimic various gangliosides, which affects the immunogenicity and the type of neurological deficits in GBS patients. Previous studies have shown the interaction of LOS with sialic acid-specific siglec receptors, although the functional consequences remain unknown. Cells that express high levels of siglecs include dendritic cells (DCs), which are crucial for initiation and differentiation of immune responses. We confirm that α2,3-sialylated GD1a/GM1a mimic and α2,8-sialylated GD1c mimic LOS structures interact with recombinant Sn and siglec-7, respectively. Although the linkage of the terminal sialic acid of LOS did not regulate expression of DC maturation markers, it displayed clear opposite expression levels of interleukin-12 (IL-12) and OX40L, molecules involved in DC-mediated Th cell differentiation. Accordingly, targeting DC-expressed siglec-7 with α2,8-linked sialylated LOS resulted in Th1 responses, whereas Th2 responses were induced by targeting with LOS containing α2,3-linked sialic acid. Thus, our data demonstrate for the first time that depending on the sialylated composition ofCampylobacter jejuniLOS, specific Th differentiation programs are initiated, possibly through targeting of distinct DC-expressed siglecs.
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

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

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

Objectives

Growing 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.

Methods

Abatement 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.

Results

City 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.

Conclusions

Tobacco 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

Objective

To determine what the tobacco industry knew about the potential effects of menthol on smoking topography—how a person smokes a cigarette.

Methods

A 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.

Results

The 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.

Conclusion

Our 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.
Tobacco and cigarette butt consumption in humans and animals
Authors: Novotny Thomas E , Hardin Sarah N , Hovda Lynn R , Novotny Dale J , McLean Mary Kay , Khan Safdar
Published: April 2011

Discarded cigarette butts may present health risks to human infants and animals because of indiscriminate eating behaviours. Nicotine found in cigarette butts may cause vomiting and neurological toxicity; leachates of cigarette butts in aquatic environments may cause exposure to additional toxic chemicals including heavy metals, ethyl phenol and pesticide residues. This report reviews published and grey literature regarding cigarette butt waste consumption by children, pets and wildlife. Although reports of human and animal exposures number in the tens of thousands, severe toxic outcomes due to butt consumption are rare. Nonetheless, the ubiquity of cigarette butt waste and its potential for adverse effects on human and animal health warrants additional research and policy interventions to reduce the stream of these pollutants in the environment.
Menthol: putting the pieces together
Authors: Lee Youn Ok , Glantz Stanton A
Published: April 2011

Objective

To 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 sources

Papers published in this supplement ofTobacco Control, together with papers identified using PubMed searches.

Results

Tobacco 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.

Conclusion

Information 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.
ν-PROJECTIVE SPACES, ν-LINE BUNDLES AND CHERN CLASSES
Authors: VARSAIE S.
Published: April 2011

Following the formalism derived from one method of constructing common projective spaces along with using a special kind of odd module homomorphisms, denoted by ν, a novel supergeometric generalization of projective spaces is constructed. Existence of canonical line bundles over these spaces and their Chern classes are discussed.
TOPOLOGICAL FOUR-DIMENSIONAL GRAVITY AND KODAMA STATE BEYOND INSTANTONS
Authors: TLAPANCO-LIMON J. F.
Published: April 2011

By using the two-component spinor formalism and the symplectic geometry of the phase space, it is shown that the Kodama state actually exist within a topological phase where the Weyl spinor does not vanish. This topological phase, belonging to the complete topological sector of general relativity (GR), is bigger than the one associated with gravitational instantons. The conditions of projection onto the sector of gravitational instantons are discussed as well.
GENERALIZATION OF THE GELL–MANN DECONTRACTION FORMULA FOR sl(n,ℝ) AND su(n) ALGEBRAS
Authors: SALOM IGOR , ŠIJAČKI DJORDJE
Published: April 2011

The so-called Gell–Mann or decontraction formula is proposed as an algebraic expression inverse to the Inönü–Wigner Lie algebra contraction. It is tailored to express the Lie algebra elements in terms of the corresponding contracted ones. In the case of sl (n,ℝ) and su (n) algebras, contracted w.r.t. so (n) subalgebras, this formula is generally not valid, and applies only in the cases of some algebra representations. A generalization of the Gell–Mann formula for sl (n,ℝ) and su (n) algebras, that is valid for all tensorial, spinorial, (non)unitary representations, is obtained in a group manifold framework of the SO(n) and/or Spin (n) group. The generalized formula is simple, concise and of ample application potentiality. The matrix elements of the [Formula: see text], i.e. SU(n)/SO(n), generators are determined, by making use of the generalized formula, in a closed form for all irreducible representations.
STABILIZED NONLINEAR DISCRETE-TIME ADAPTIVE CONTROLLER BASED ON FUZZY RULES EMULATED NETWORKS AND TIME VARYING LEARNING RATE
Authors: TREESATAYAPUN C.
Published: April 2011

A direct adaptive controller based on fuzzy rules emulated network (FREN) for a class of unknown nonlinear discrete-time systems is addressed in this article. According to the fuzzy inference system inside FREN, the human knowledge about the unknown systems is transferred to be if–then rules for setting the network structure. All adjustable parameters are tuned by the on-line learning mechanism with time varying learning rate. This variation of learning rate is introduced by main theorem to improve the system performance and stabilization. Furthermore, the convergence of adjustable parameters is guaranteed through the on-line learning and membership functions properties. The theoretical validation is delineated by the experimental setup with the commercial omni-directional mobile robot system.
Ability-Based Design
Authors: Wobbrock Jacob O. , Kane Shaun K. , Gajos Krzysztof Z. , Harada Susumu , Froehlich Jon
Published: April 2011

Current approaches to accessible computing share a common goal of making technology accessible to users with disabilities. Perhaps because of this goal, they may also share a tendency to centralize disability rather than ability. We present a refinement to these approaches called
ability-based design
that consists of focusing on ability throughout the design process in an effort to create systems that leverage the full range of human potential. Just as user-centered design shifted the focus of interactive system design from systems to users, ability-based design attempts to shift the focus of accessible design from disability to ability. Although prior approaches to accessible computing may consider users’ abilities to some extent, ability-based design makes ability its central focus. We offer seven ability-based design principles and describe the projects that inspired their formulation. We also present a research agenda for ability-based design.
Spindex (Speech Index) Improves Auditory Menu Acceptance and Navigation Performance
Authors: Jeon Myounghoon , Walker Bruce N.
Published: April 2011

Users interact with mobile devices through menus, which can include many items. Auditory menus have the potential to make those devices more accessible to a wide range of users. However, auditory menus are a relatively new concept, and there are few guidelines that describe how to design them. In this paper, we detail how visual menu concepts may be applied to auditory menus in order to help develop design guidelines. Specifically, we examine how to optimize the designs of a new contextual cue, called “spindex” (i.e., speech index). We developed and evaluated various design alternatives for spindex and iteratively refined the design with sighted users and visually impaired users. As a result, the “attenuated” spindex was the best in terms of preference as well as performance, across user groups. Nevertheless, sighted and visually impaired participants showed slightly different responses and feedback. Results are discussed in terms of acoustical theory, practical display design, and assistive technology design.
Two-way TCP connections
Authors: Heusse Martin , Merritt Sears A. , Brown Timothy X. , Duda Andrzej
Published: April 2011

Many papers explain the drop of download performance when two TCP connections in opposite directions share a common bottleneck link by ACK compression, the phenomenon in which download ACKs arrive in bursts so that TCP self clocking breaks. Efficient mechanisms to cope with the performance problem exist and we do not consider proposing yet another solution. We rather thoroughly analyze the interactions between connections and show that actually ACK compression only arises in a perfectly symmetrical setup and it has little impact on performance. We provide a different explanation of the interactions---data pendulum, a core phenomenon that we analyze in this paper. In the data pendulum effect, data and ACK segments alternately fill only one of the link buffers (on the upload or download side) at a time, but almost never both of them. We analyze the effect in the case in which buffers are structured as arrays of bytes and derive an expression for the ratio between the download and upload throughput. Simulation results and measurements confirm our analysis and show how appropriate buffer sizing alleviates performance degradation. We also consider the case of buffers structured as arrays of packets and show that it amplifies the effects of data pendulum.
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.
Designing and embedding reliable virtual infrastructures
Authors: Yeow Wai-Leong , Westphal Cedric , Kozat Ulas C.
Published: April 2011

In a virtualized infrastructure where physical resources are shared, a single physical server failure will terminate several virtual servers and crippling the virtual infrastructures which contained those virtual servers. In the worst case, more failures may cascade from overloading the remaining servers. To guarantee some level of reliability, each virtual infrastructure, at instantiation, should be augmented with backup virtual nodes and links that have sufficient capacities. This ensures that, when physical failures occur, sufficient computing resources are available and the virtual network topology is preserved. However, in doing so, the utilization of the physical infrastructure may be greatly reduced. This can be circumvented if backup resources are pooled and shared across multiple virtual infrastructures, and intelligently embedded in the physical infrastructure. These techniques can reduce the physical footprint of virtual backups while guaranteeing reliability.
Dual Specificity Phosphatase 1 Regulates Human Inducible Nitric Oxide Synthase Expression by p38 MAP Kinase
Authors: Turpeinen Tuija , Nieminen Riina , Taimi Ville , Heittola Taina , Sareila Outi , Clark Andrew R. , Moilanen Eeva , Korhonen Riku
Published: April 2011

The role of dual specificity phosphatase 1 (DUSP1) in inducible nitric oxide synthase (iNOS) expression in A549 human pulmonary epithelial cells, J774 mouse macrophages and primary mouse bone marrow-derived macrophages (BMMs) was investigated. iNOS expression was induced by a cytokine mixture (TNF, IFNγ and IL-1β) in A549 cells and by LPS in J774 cells, and it was inhibited by p38 MAPK inhibitors SB202190 and BIRB 796. Stimulation with cytokine mixture or LPS enhanced also DUSP1 expression. Down-regulation of DUSP1 by siRNA increased p38 MAPK phosphorylation and iNOS expression in A549 and J774 cells. In addition, LPS-induced iNOS expression was enhanced in BMMs from DUSP1(−/−)mice as compared to that in BMMs from wild-type mice. The results indicate that DUSP1 suppresses iNOS expression by limiting p38 MAPK activity in human and mouse cells. Compounds that enhance DUSP1 expression or modulate its function may be beneficial in diseases complicated with increased iNOS-mediated NO production.
A Note on Iwasawa‐Type Decomposition
Authors: Foth Philip
Published: April 2011

We study the Iwasawa‐type decomposition of an open subset of SL(n, ℂ) as SU(p, q)AN. We show that the dressing action of SU(p, q) is globally defined on the
space of admissible elements in AN. We also show that the space of admissible elements
is a multiplicative subset of AN. We establish a geometric criterion: the symmetrization
of an admissible element maps the positive cone in ℂn into itself.
mRNA/microRNA Profile at the Metamorphic Stage of Olive Flounder (Paralichthys olivaceus)
Authors: Xie Caixia , Xu Shanliang , Yang Linlin , Ke Zhonghe , Xing Jubin , Gai Junwei , Gong Xiaoling , Xu Liuxiong , Bao Baolong
Published: April 2011

Flatfish is famous for the asymmetric transformation during metamorphosis. The molecular mechanism behind the asymmetric development has been speculated over a century and is still not well understood. To date, none of the metamorphosis-related genes has been identified in flatfish. As the first step to screen metamorphosis-related gene, we constructed a whole-body cDNA library and a whole-body miRNA library in this study and identified 1051 unique ESTs, 23 unique miRNAs, and 4 snoRNAs in premetamorphosing and prometamorphosingParalichthys olivaceus. 1005 of the ESTs were novel, suggesting that there was a special gene expression profile at metamorphic stage. Four miRNAs (pol-miR-20c,pol-miR-23c,pol-miR-130d, andpol-miR-181e) were novel toP. olivaceus; they were characterized as highly preserved homologies of published miRNAs but with at least one nucleotide differed. Representative 24 mRNAs and 23 miRNAs were quantified during metamorphosis ofP. olivaceusby using quantitative RT PCR or stem-loop qRT PCR. Our results showed that 20 of mRNAs might be associated with early metamorphic events, 10 of mRNAs might be related with later metamorphic events, and 16 of miRNAs might be involved in the regulation of metamorphosis. The data provided in this study would be helpful for further identifying metamorphosis-related gene inP. olivaceus.
Roles of the WHHL Rabbit in Translational Research on Hypercholesterolemia and Cardiovascular Diseases
Authors: Kobayashi Tsutomu , Ito Takashi , Shiomi Masashi
Published: April 2011

Conquering cardiovascular diseases is one of the most important problems in human health. To overcome cardiovascular diseases, animal models have played important roles. Although the prevalence of genetically modified animals, particularly mice and rats, has contributed greatly to biomedical research, not all human diseases can be investigated in this way. In the study of cardiovascular diseases, mice and rats are inappropriate because of marked differences in lipoprotein metabolism, pathophysiological findings of atherosclerosis, and cardiac function. On the other hand, since lipoprotein metabolism and atherosclerotic lesions in rabbits closely resemble those in humans, several useful animal models for these diseases have been developed in rabbits. One of the most famous of these is the Watanabe heritable hyperlipidemic (WHHL) rabbit, which develops hypercholesterolemia and atherosclerosis spontaneously due to genetic and functional deficiencies of the low‐density lipoprotein (LDL) receptor. The WHHL rabbit has been improved to develop myocardial infarction, and the new strain was designated the myocardial infarction‐prone WHHL (WHHLMI) rabbit. This review summarizes the importance of selecting animal species for translational research in biomedical science, the development of WHHL and WHHLMI rabbits, their application to the development of hypocholesterolemic and/or antiatherosclerotic drugs, and future prospects regarding WHHL and WHHLMI rabbits.
Effect of Magnetic Resonance Imaging on Breast Conservation Therapy versus Mastectomy: A Review of the Literature
Authors: Painter Thomas J. , DiPasco Peter J. , Misra Subhasis , Avisar Eli
Published: April 2011

The utilization of MRI in the workup of breast cancer has played a controversial role in the surgical treatment of this disease. With the higher resolution of breast tissue afforded, additional lesions are being identified that often warrant additional procedures, subsequently affecting the decision to proceed with breast conservation therapy versus mastectomy. In this paper, a literature review is presented to help illuminate some of the benefits and pitfalls of employing MRI as a diagnostic tool in the care of breast cancer, while additionally providing insight into the management alterations this imaging modality can engender. Though further research is required in a randomized prospective form to fully answer this question, evidence for and against its use continues to mount, especially for select patient groups.
PolyAlign: A Versatile LC-MS Data Alignment Tool for Landmark-Selected and -Automated Use
Authors: Vähämaa Heidi , Koskinen Ville R. , Hosia Waltteri , Moulder Robert , Nevalainen Olli S. , Lahesmaa Riitta , Aittokallio Tero , Salmi Jussi
Published: April 2011

We present a versatile user-friendly software tool, PolyAlign, for the alignment of multiple LC-MS signal maps with the option of manual landmark setting or automated alignment. One of the spectral images is selected as a reference map, and after manually setting the landmarks, the program warps the images using either polynomial or Hermite transformation. The software provides an option for automated landmark finding. The software includes a very fast zoom-in function synchronized between the images, which facilitate detecting correspondences between the adjacent images. Such an interactive visual process enables the analyst to decide when the alignment is satisfactory and to correct known irregularities. We demonstrate that the software provides significant improvements in the alignment of LC-MALDI data, with 10–15 landmark pairs, and it is also applicable to correcting electrospray LC-MS data. The results with practical data show substantial improvement in peak alignment compared to MZmine, which was among the best analysis packages in a recent assessment. The PolyAlign software is freely available and easily accessible as an integrated component of the popular MZmine software, and also as a simpler stand-alone Perl implementation to preview data and apply landmark directed polynomial transformation.
Histological Consequences of Needle-Nerve Contact following Nerve Stimulation in a Pig Model
Authors: Steinfeldt T. , Graf J. , Schneider J. , Nimphius W. , Weihe E. , Borgeat A. , Wulf H. , Wiesmann T.
Published: April 2011

Background. Nerve stimulation can facilitate correct needle placement in peripheral regional anesthesia. The aim of this study was to determine whether the high threshold current is associated with reduced nerve injury due to fewer needle-nerve contacts compared with low current.Methods. In anaesthetized pigs, thirty-two nerves of the brachial plexus underwent needle placement at low (0.2 mA) or high current (1.0 mA). The occurrence of needle-nerve contact was recorded. After 48 hours, the nerves were analyzed for occurrence of histological changes. Nerve injury was scored ranging from 0 (no injury) to 4 (severe injury).Results. The frequency of needle-nerve contact was 94% at low compared to 6% at high current. The score was significantly higher at low (median [interquartile range] 2.0 [1.0-2.0]) compared to high current (0.0 [0.0-1.0]P=.001).Conclusions. Inflammatory responses were directly related to needle-nerve contacts. Hence, posttraumatic inflammation may be diminished using higher current for nerve localization.
Lymphomatoid Granulomatosis Treated Successfully with Rituximab in a Renal Transplant Patient
Authors: Castrale Cindy , El Haggan Wael , Chapon Françoise , Reman Oumedaly , Lobbedez Thierry , Ryckelynck Jean Philippe , Hurault de Ligny Bruno
Published: April 2011

Lymphomatoid granulomatosis (LYG) in renal transplant recipients is rare multisystemic angiocentric lymphoproliferative disorder with significant malignant potential. Here, we describe LYG in a 70-year-old renal allograft recipient who, 4 years after transplantation, on tacrolimus and mycophenolate mofetil and prednisone maintenance immunosuppression, complained of low-grade fever, persistent headache and gait disturbance. The MRI of the brain revealed diffuse periventricular cerebral and cerebellar contrast-enhanced lesions. The CT scan of the thorax showed multiple pulmonary nodular opacities in both lung fields. The patient was diagnosed LYG based on the cerebral biopsy showing perivascular infiltration of CD20-positive B-lymphocytes with granulomatous lesions and immunofluorescence staining with anti-EBV antibodies. With careful reduction of the immunossuppression combined with the use of rituximab, our patient showed a complete disappearance of LYG, and she is clinically well more than 4 years after the diagnosis, with good kidney function. No recurrence has been observed by radiological imaging until now. This is the first report of a durable (>4 years) complete remission of LYG after treatment with rituximab in renal transplantation.
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

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

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.
The Future in Diagnosis and Staging of Lung Cancer: Positron Emission Tomography
Authors: Fischer Barbara M. , Mortensen Jann
Published: April 2011

Since its introduction in 1974, positron emission tomography (PET) has gained widespread use, especially in diagnosis and staging of lung cancer. In this respect, 18F-fluorodeoxyglucose (FDG) is by far the most used PET tracer exploiting the increased glucose uptake and metabolism in malignant cells. A large number of studies have suggested that addition of FDG-PET to conventional workup can improve diagnosis and staging in patients with non-small cell lung cancer (NSCLC). In meta-analysis, the sensitivity and specificity of PET in diagnosing single pulmonary nodules and masses is found to be 96 and 78%, respectively. In mediastinal staging, the sensitivity and specificity of PET is estimated to be 83 and 92%. In order to achieve high diagnostic values from PET, it is necessary to pay attention to a number of pitfalls, e.g., the uptake of FDG by inflammatory cells causing false-positive results, as well as size and histology of the tumour in order to avoid false-negative results. In 2001, the first integrated PET/computed tomography (CT) was installed, and since then, the use of this modality has expanded steadily, thereby decreasing examination time and overcoming the lack of anatomical details on PET. Recently, PET and PET/CT have become increasingly integrated in therapy planning and evaluation: response evaluation during and after chemotherapy, restaging after neoadjuvant therapy, planning of radiotherapy and detection of recurrent disease are all examples of emerging indications for PET and PET/CT in managing patients with lung cancer.
Symptoms in the Lives of Terminal Cancer Patients: Which Is the Most Important?
Authors: Kwon Yong Chol , Yun Young Ho , Lee Ki Heon , Son Ki Young , Park Sang Min , Chang Yoon Jung , Wang Xin Shelley , Mendoza Tito R. , Cleeland Charles S.
Published: April 2011

Objectives: Symptoms other than their primary disease can interfere in the lives of terminal cancer patients. We sought to identify which of these symptoms is most important. Methods: We administered a questionnaire, including the M.D. Anderson Symptom Inventory (MDASI), to 142 terminal cancer patients at the National Cancer Center, Korea. The validity of the MDASI was tested by principal-axis factor analysis and Cronbach’s α coefficient. Stepwise multiple regression analysis was used to determine the symptoms that interfered most in terminal cancer patients’ lives. Results: Factor analysis showed that it was composed of two factors (symptom and interference scales). Cronbach’s α coefficients of symptom and interference scales were each >0.70. The patients had an average of 11 of 13 symptoms of the MDASI. Pain was the most common and severe, followed by feelings of distress and fatigue. Fatigue was the most highly correlated with interference sum. In stepwise multiple regression analysis, the most interfering symptom was fatigue. Conclusions: Although pain was the most common and severe symptom, fatigue was the most important symptom interfering in the lives of terminal cancer patients. In treating terminal cancer patients, healthcare providers should actively intervene to reduce both fatigue and pain.
Graft versus Host Disease after Orthotopic Liver Transplantation Documented by Analysis of Short Tandem Repeat Polymorphisms
Authors: Schöniger-Hekele M. , Müller C. , Kramer L. , Dauber E. , Mayr W.R. , Wrba F. , Rockenschaub S. , Mühlbacher F.
Published: April 2011

We report a case of graft versus host disease after liver transplantation in which the diagnosis was made by short tandem repeat analysis. A retrospective analysis using a bone marrow sample showed the presence of chimerism already at a time when the characteristic full clinical picture of graft versus host disease had not yet developed, opening the way for the early diagnosis and treatment.
Leadership, Mental Health, and Organizational Efficacy in Health Care Organizations
Authors: Arnetz Bengt , Blomkvist Vanja
Published: April 2011

Background: Only a few studies of psychosocial determinants of employee health and organizational development have been prospective, involving more than one organization and applying standardized assessment tools. This limits the ability of providing evidence-based guidance as how to carry out healthy organizational transformations. Methods: A total of 6,000 employees responded twice to a validated psychosocial-leadership questionnaire within a 2-year period. The assessment focused on changes over time in the three outcome measures – mental health, efficacy, and leadership, determined to be important indicators of a healthy organization. Changes within and between organization were assessed statistically using regular t tests and general linear modeling. Results: There were major differences between organizations in psychosocial measures, both at the baseline and over time. At the organizational level, changes between study periods in management performance feedback, participatory management, and work tempo were the most consistent predictors of improvements over time in the three outcome measures. Conclusions: Performance feedback and participatory management might be two common predictors of healthy workplaces. Some of the psychosocial determinants of healthy organizations suggested in previous research might not be universally valid. It is suggested that future research should to a larger degree make use of multiple departments and organizations in studies of psychosocial determinants of healthy organizations.
Are Marketed Topical Metronidazole Creams Bioequivalent? Evaluation by in vivo Microdialysis Sampling and Tape Stripping Methodology
Authors: García Ortiz P. , Hansen S.H. , Shah V.P. , Sonne J. , Benfeldt E.
Published: April 2011

Aim: To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence. Methods: Nine microdialysis probes were inserted in the volar aspect of the left forearm of 14 healthy volunteers and, following application of the 3 metronidazole creams, microdialysis samples were collected for 5 h. On the right forearm, tape strip sampling was performed 30 and 120 min after product application. At the end of the experiment, ultrasound scanning measurements confirmed that all probes were placed inside the dermis. Results: There was no statistical difference in penetration of the 3 topicals as determined by microdialysis. However, their bioequivalence could not be determined due to intersubject variability exceeding the criteria for bioequivalence evaluation. Tape strip sampling established a bioequivalence between 2 of the creams, but rejected any bioequivalence between these 2 formulations and the third. The third formulation was a generic formulation approved despite containing a lower concentration of metronidazole (0.75%) than the innovator formulation (1.0%). The result of the bioequivalence evaluation depends on the methodology employed. Conclusion: Whenever the dermis is the target tissue, microdialysis provides the most relevant information on drug bioavailability.
Adult Isolated Congenital Anterior Urethrocutaneous Fistula
Authors: Chen Qiang , Xiao Wen-Lin , Jiang Yong-Mei , Sun Li-Jiang
Published: April 2011

Isolated congenital anterior urethrocutaneous fistula (CAUF) is an extremely rare deformity and few cases have been reported in the English language literature. Moreover, adult CAUF has not been reported up to now. We present a rare adult patient with this unusual isolated CAUF deformity. The possible etiology and treatment strategy are discussed.
Plasmacytoid Urothelial Carcinoma of the Bladder: A Rare Malignancy
Authors: Philippou Prodromos , Kariotis Ioannis , Volanis Demetrios , Ploumides Achilleas , Delakas Demetrios
Published: April 2011

In 2004, the WHO recognized the plasmacytoid subtype as a distinct variant of vesical malignancy. We present a case of plasmacytoid urothelial carcinoma of the bladder treated with radical surgery and adjuvant chemotherapy, thus achieving long-term survival. A 70-year-old woman presented with persistent dysuria and underwent cystoscopy which revealed the presence of diffuse deformity, involving the right lateral vesical wall. Histology revealed the presence of muscle-invasive urothelial carcinoma of the plasmacytoid variant. The patient subsequently underwent radical cystectomy and orthotopic ileal neobladder substitution, as well as adjuvant chemotherapy. At 36 months of follow-up, the patient is free of local recurrence and metastases, while her voiding function is well preserved. Bladder plasmacytoid urothelial carcinoma is considered a rare tumor, with unique microscopic and immunohistochemical features. The ideal therapeutic approach is debatable, but the combination of radical surgery and chemotherapy should constitute the mainstay of management.
Initial Experience with Temsirolimus in 2nd-, 3rd- and 4th-Line Therapy for Metastatic Renal Cell Cancer: Good Clinical Response
Authors: Kuru Timur Hasan , Huber Johannes , Hatiboglu Gencay , Wagener Nina , Pahernik Sascha , Hadaschik Boris , Hohenfellner Markus
Published: April 2011

Purpose: To report our experience with temsirolimus in 2nd-, 3rd- and 4th-line therapy for patients with metastatic renal cell carcinoma (mRCC). Patients and Methods: In our prospectively maintained tumor registry, we identified 6 mRCC patients with temsirolimus in >1st-line systemic therapy. Patients were followed by weekly clinical and laboratory examination during admission of temsirolimus. Re-staging with chest CT and abdominal MRI was performed every 3 months. Results: We observed excellent response rates. Progression-free survival (PFS) ranged from 6 to 40 months with a median of 15 months. Treatment was generally well tolerated. However, pneumonitis was observed in 4 of 6 patients. Drug-related pneumonitis led to severe dyspnea, with the result that treatment with temsirolimus had to be interrupted for a short period of time in 2 patients and discontinued in 1 patient. Conclusions: Temsirolimus proved to be a very good treatment option in 2nd- to 4th-line therapy with excellent response rates and manageable side effects. The incidence of pneumonitis must not be underestimated.
Long-Term Efficacy of Serenoa repens Treatment in Patients with Mild and Moderate Symptomatic Benign Prostatic Hyperplasia
Authors: Sinescu Ioanel , Geavlete Petrisor , Multescu Razvan , Gangu Constantin , Miclea Florin , Coman Ioan , Ioiart Ioan , Ambert Valentin , Constantin Traian , Petrut Bogdan , Feciche Bogdan
Published: April 2011

Introduction: The study aimed to evaluate the long-term efficacy of treatment with extract of Serenoa repens (Prostamol Uno) in patients with lower urinary tract symptoms (LUTS) induced by benign prostatic hyperplasia (BPH). Patients and Methods: We studied 120 patients with mild or moderate LUTS induced by BPH, maximal urinary flow (Qmax) <15 ml with a voided volume ≧150 ml, prostate-specific antigen <4 ng/ml, and residual urinary volume <150 ml, treated daily for 24 months with one capsule of 320 mg ethanolic extract of Serenoa repens. Results: Statistically significant improvements in the International Prostate Symptom Score (5.5 points), quality of life (QoL; 1.8 points), Qmax (5.6 ml/s), International Index of Erectile Function (IIEF; 6.4 points) and reduction in residual urinary volume were observed during the study period. The mean prostate volume at 24 months was 36 ml, compared to 39.8 ml at baseline. Conclusions: Long-term treatment with 320 mg ethanolic extract of Serenoa repens proved to be efficient in reducing urinary obstruction, improving symptomatology and QoL of BPH patients. It also had a positive effect on sexual function, demonstrated by the statistically significant increase in the IIEF.