bluuebunny/crossref_metadata_2025 huggingface dataset:
A review of some recent developments in robust regression
Authors: Wilcox Rand R.
Published: August 2011

In situations where the goal is to understand how a random variable y is related to a set of p predictor variables, modern robust regression methods can be invaluable. One reason is that even one unusual value in the design space, or one outlier among the y values, can have a large impact on the ordinary least squares estimate of the parameters of the usual linear model. That is, a single unusual value or outlier can give a highly distorted view of how two or more random variables are related. Another reason is that modern robust methods can be much more efficient than ordinary least squares yet maintain good efficiency under the ideal conditions of normality and a homoscedastic error term. Even when sampling is from light‐tailed distributions, there are situations where certain robust methods are highly efficient compared to least squares, as is indicated in this paper. Most applied researchers in psychology simply ignore these problems. In the hope of improving current practice, this paper reviews some of the robust methods currently available with an emphasis on recent developments. Of particular interest are methods for computing confidence intervals and dealing with heteroscedasticity in the error term.
Some practical reasons for reconsidering the Kolmogorov‐Smirnov test
Authors: Wilcox Rand R.
Published: August 2011

The Kolmogorov‐Smirnov test is a method for comparing the distributions of two independent groups that has virtually disappeared from applied research and introductory statistics books for the social sciences. The apparent reason is the perception that it has low power compared to methods for comparing means in particular and measures of location in general. However, extant studies comparing the power of the Kolmogorov‐Smirnov test to other methods for comparing means are limited to normal distributions having a common variance. This note points out that, even under a shift model, the Kolmogorov‐Smirnov test not only can have high power relative to methods for comparing robust measures of location, there are situations where it has higher power than methods for comparing robust measurement of location. Some additional features of the Kolmogorov‐Smirnov test are noted, and a simple S‐PLUS program for computing the exact significance level is provided. Data from a study on the effects of drinking alcohol are used to illustrate the potential advantage of the Kolmogorov‐Smirnov test.
Extra‐binomial variation in multilevel logistic models with sparse structures
Authors: Wright Daniel B.
Published: August 2011

When discrete response models arc estimated with multilevel, or clustered, data, there is much interest in the distribution of the residuals. With logistic regression it is usually assumed that these residuals are binomially distributed. A common real world situation is where the multilevel data structure is sparse, with relatively few individual cases per cluster. The impact of sparsity on estimates of binomial variation is explored using simulation techniques. This exploration demonstrates that sparsity leads to extra‐binomial variation. The results are discussed in relation to recent data on eyewitness line‐ups, an example with a sparse data structure.
Bayesian sampling‐based approach for factor analysis models with continuous and polytomous data
Authors: Shi Jian‐Qing , Lee Sik‐Yum
Published: August 2011

Factor analysis is an important technique in behavioural science research in explaining the interdependence and assessing causations and correlations of the observed variables and the latent factors. Recently, generalization of the model to handle polytomous variables has received a lot of attention. In this paper, a Bayesian approach to analysing the model with continuous and polytomous variables is developed. In the posterior analysis, the observed continuous and polytomous data are augmented with the latent factor scores and the unobserved measurements underlying the polytomous variables. Random observations from the posterior distributions are simulated via the Gibbs sampler algorithm. It is shown that the conditional distributions involved in the implementation of the algorithm are the familiar distributions, hence the simulation is rather straightforward. Joint Bayesian estimates of the unknown thresholds, structural parameters and the factor scores are produced simultaneously. The efficiency and accuracy of our approach are demonstrated by a real‐life example and a simulation study.
Normal theory based test statistics in structural equation modelling
Authors: Yuan Ke‐Hai , Bentler Peter M.
Published: August 2011

Even though data sets in psychology are seldom normal, the statistics used to evaluate covariance structure models are typically based on the assumption of multivariate normality. Consequently, many conclusions based on normal theory methods are suspect. In this paper, we develop test statistics that can be correctly applied to the normal theory maximum likelihood estimator. We propose three new asymptotically distribution‐free (ADF) test statistics that technically must yield improved behaviour in samples of realistic size, and use Monte Carlo methods to study their actual finite sample behaviour. Results indicate that there exists an ADF test statistic that also performs quite well in finite sample situations. Our analysis shows that various forms of ADF test statistics are sensitive to model degrees of freedom rather than to model complexity. A new index is proposed for evaluating whether a rescaled statistic will be robust. Recommendations are given regarding the application of each test statistic.
The Future of Seawater Desalination: Energy, Technology, and the Environment
Authors: Elimelech Menachem , Phillip William A.
Published: August 2011

In recent years, numerous large-scale seawater desalination plants have been built in water-stressed countries to augment available water resources, and construction of new desalination plants is expected to increase in the near future. Despite major advancements in desalination technologies, seawater desalination is still more energy intensive compared to conventional technologies for the treatment of fresh water. There are also concerns about the potential environmental impacts of large-scale seawater desalination plants. Here, we review the possible reductions in energy demand by state-of-the-art seawater desalination technologies, the potential role of advanced materials and innovative technologies in improving performance, and the sustainability of desalination as a technological solution to global water shortages.
A 10,000-Year Record of Arctic Ocean Sea-Ice Variability—View from the Beach
Authors: Funder Svend , Goosse Hugues , Jepsen Hans , Kaas Eigil , Kjær Kurt H. , Korsgaard Niels J. , Larsen Nicolaj K. , Linderson Hans , Lyså Astrid , Möller Per , Olsen Jesper , Willerslev Eske
Published: August 2011

Sea-ice coverage near northern Greenland and in the western Arctic Ocean varied in opposition over much of the Holocene.
Chemical Genomic Profiling for Antimalarial Therapies, Response Signatures, and Molecular Targets
Authors: Yuan Jing , Cheng Ken Chih-Chien , Johnson Ronald L. , Huang Ruili , Pattaradilokrat Sittiporn , Liu Anna , Guha Rajarshi , Fidock David A. , Inglese James , Wellems Thomas E. , Austin Christopher P. , Su Xin-zhuan
Published: August 2011

There are a limited number of ways that the malaria parasite can develop drug resistance.
Nonreciprocal Light Propagation in a Silicon Photonic Circuit
Authors: Feng Liang , Ayache Maurice , Huang Jingqing , Xu Ye-Long , Lu Ming-Hui , Chen Yan-Feng , Fainman Yeshaiahu , Scherer Axel
Published: August 2011

An engineered metallic-silicon waveguide allows for direction-dependent light propagation.
Mind Your Language
Metaphors for Environmental Sustainability
Redefining Our Relationship with Nature

by Brendon Larson

Yale University Press, New Haven, CT, 2011. 317 pp. $40, £28. ISBN 9780300151534.
Authors: Golubiewski Nancy
Published: August 2011

Exploring the interplay of language and science, Larson focuses on how metaphors sway prospects for environmental sustainability.
Seeing a Molecular Motor at Work
Authors: Junge Wolfgang , Müller Daniel J.
Published: August 2011

Atomic force microscopy reveals conformational changes in a rotary molecular motor.
A Conformational Change of C Fragment of Tetanus Neurotoxin Reduces Its Ganglioside-Binding Activity but Does Not Destroy Its Immunogenicity
Authors: Yu Rui , Yi Shaoqiong , Yu Changming , Fang Ting , Liu Shuling , Yu Ting , Song Xiaohong , Fu Ling , Hou Lihua , Chen Wei
Published: August 2011

The C fragment of tetanus neurotoxin (TeNT-Hc) with different conformations was observed due to the four cysteine residues within it which could form different intramolecular disulfide bonds. In this study, we prepared and compared three types of monomeric TeNT-Hc with different conformational components: free sulfhydryls (50 kDa), bound sulfhydryls (44 kDa), and a mixture of the two conformational proteins (half 50 kDa and half 44 kDa). TeNT-Hc with bound sulfhydryls reduced its binding activity to ganglioside GT1band neuronal PC-12 cells compared to what was seen for TeNT-Hc with free sulfhydryls. However, there was no significant difference among their immunogenicities in mice, including induction of antitetanus toxoid IgG titers, antibody types, and protective capacities against tetanus neurotoxin challenge. Our results showed that the conformational changes of TeNT-Hc resulting from disulfide bond formation reduced its ganglioside-binding activity but did not destroy its immunogenicity, and the protein still retained continuous B cell and T cell epitopes; that is, the presence of the ganglioside-binding site within TeNT-Hc may be not essential for the induction of a fully protective antitetanus response. TeNT-Hc with bound sulfhydryls may be developed into an ideal human vaccine with a lower potential for side effects.
Evaluation of a Novel Multiplex Human Papillomavirus (HPV) Genotyping Assay for HPV Types in Skin Warts
Authors: Schmitt Markus , de Koning Maurits N. C. , Eekhof Just A. H. , Quint Wim G. V. , Pawlita Michael
Published: August 2011

Human papillomaviruses (HPV) of the genera alpha, mu, and nu induce benign tumors of the cutaneous epithelia that constitute a significant burden for immunocompromised adults. Currently, no gold standard for genotyping of these HPV types exists. In this study, we describe the prevalence of genus alpha, mu, and nu HPV types in cutaneous warts. We developed a novel multiplex HPV genotyping assay, BSwart-PCR/MPG (BSwart), to type sensitively and specifically 19 cutaneous HPV types frequently found in warts. BSwart-PCR/MPG is based on a multiplex PCR using broad-spectrum primers and subsequent multiplex hybridization to type-specific probes coupled to Luminex beads. In a first application comprising 100 cutaneous warts, the assay was compared to another, recently described genotyping assay, the HSL-PCR/MPG. When a 10-fold dilution series was used, the detection limit was between 10 and 100 HPV genomes per PCR. When comparing the two assays, there was an excellent agreement in detecting dominant HPV types; however, we also obtained evidence for a higher sensitivity of the BSwart assay for multiple infections in these cutaneous warts. Using BSwart, HPV was found in 95% of wart preparations, with HPV1 being most prevalent, followed by types 27, 57, and 2. Both novel BSwart and HSL-PCR/MPG HPV genotyping assays are powerful high-throughput tools that could be used to learn more about the natural history of cutaneous HPV. They would be advantageous to monitor the efficacy of future skin HPV vaccines and to identify novel HPV vaccine candidates.
Alaska Sentinel Surveillance Study of Helicobacter pylori Isolates from Alaska Native Persons from 2000 to 2008
Authors: Tveit Adrienne H. , Bruce Michael G. , Bruden Dana L. , Morris Julie , Reasonover Alisa , Hurlburt Debby A. , Hennessy Thomas W. , McMahon Brian
Published: August 2011

Helicobacter pylori
infection is more common in Alaska Native persons than in the general U.S. population, with seroprevalence to
H. pylori
approaching 75%. Previous studies in Alaska have demonstrated elevated proportions of antimicrobial resistance among
H. pylori
isolates. We analyzed
H. pylori
data from the Centers for Disease Control and Prevention's sentinel surveillance in Alaska from January 2000 to December 2008 to determine the proportion of culture-positive biopsy specimens with antimicrobial resistance from Alaska Native persons undergoing endoscopy. The aim of the present study was to monitor antimicrobial resistance of
H. pylori
isolates over time and by region in Alaska Native persons. Susceptibility testing of
H. pylori
isolates to metronidazole, clarithromycin, amoxicillin, and tetracycline was performed using agar dilution. Susceptibility testing for levofloxacin was performed by Etest. Overall, 45% (532/1,181) of persons undergoing upper endoscopy were culture positive for
H. pylori
. Metronidazole resistance was demonstrated in isolates from 222/531 (42%) persons, clarithromycin resistance in 159/531 (30%) persons, amoxicillin resistance in 10/531 (2%) persons, and levofloxacin resistance in 30/155 (19%) persons; no tetracycline resistance was documented. The prevalence of metronidazole, clarithromycin, and levofloxacin resistance varied by region. Female patients were more likely than male patients to demonstrate metronidazole (
P
< 0.05) and clarithromycin (
P
< 0.05) resistance. No substantial change in the proportion of persons with resistant isolates was observed over time. Resistance to metronidazole, clarithromycin, and levofloxacin is more common among
H. pylori
isolates from Alaska Native persons than those from elsewhere in the United States.
Role of the Endocytic Pathway in the Counteraction of BST-2 by Human Lentiviral Pathogens
Authors: Lau David , Kwan Wilson , Guatelli John
Published: August 2011

The interferon-inducible transmembrane protein BST-2 (CD317, tetherin) restricts the release of several enveloped viruses from infected cells. BST-2 is broadly active against retroviruses, including HIV-1 and HIV-2. To counteract this host defense, HIV-1 uses the accessory protein Vpu, whereas HIV-2 uses its envelope glycoprotein (Env). In both cases, viral antagonism is associated with decreased expression of BST-2 at the cell surface. Here, we provide evidence supporting a role for the clathrin-mediated endocytic pathway in the downregulation of BST-2 from the cell surface and the counteraction of restricted virion release. A catalytically inactive, dominant negative version of the vesicle “pinch-ase” dynamin 2 (dyn2K44A) inhibited the downregulation of BST-2 by Vpu, and it inhibited the release of wild-type (Vpu-expressing) HIV-1 virions. Similarly, dyn2K44A inhibited the downregulation of BST-2 by HIV-2 Env, and it inhibited the release of
vpu
-negative HIV-1 virions when HIV-2 Env was provided in
trans
. dyn2K44A inhibited Env more robustly than Vpu, suggesting that dynamin 2, while a cofactor for both Env and Vpu, might support just one of several pathways though which Vpu counteracts BST-2. In support of a role for clathrin in these effects, the C-terminal domain of the clathrin assembly protein AP180 also inhibited the downregulation of BST-2 by either Vpu or HIV-2 Env. Consistent with modulation of the postendocytic itinerary of BST-2, Vpu enhanced the accumulation of cell surface-derived BST-2 in transferrin-containing endosomes. Vpu also inhibited the transport of BST-2 from a brefeldin A-insensitive compartment to the cell surface, consistent with a block to endosomal recycling. We propose that HIV-1 Vpu, and probably HIV-2 Env, traps BST-2 in an endosomal compartment following endocytosis, reducing its level at the cell surface to counteract restricted viral release.
Mechanisms Governing the Selection of Translation Initiation Sites on Foot-and-Mouth Disease Virus RNA
Authors: Pöyry Tuija A. A. , Jackson Richard J.
Published: August 2011

Translation initiation dependent on the foot-and-mouth disease virus (FMDV) internal ribosome entry site (IRES) occurs at two sites (Lab and Lb), 84 nucleotides (nt) apart.
In vitro
translation of an mRNA comprising the IRES and Lab-Lb intervening segment fused to a chloramphenicol acetyltransferase (CAT) reporter has been used to study the parameters influencing the ratio of the two products and the combined product yield as measures of relative initiation site usage and productive ribosome recruitment, respectively. With wild-type mRNA, ∼40% of initiation occurred at the Lab site, which was increased to 90% by optimization of its context, but decreased to 20% by mutations that reduced downstream secondary structure, with no change in recruitment in either case. Inserting 5 nt into the pyrimidine-rich tract located just upstream of the Lab site increased initiation at this site by 75% and ribosome recruitment by 50%. Mutating the Lab site to RCG or RUN codons decreased recruitment by 20 to 30% but stimulated Lb initiation by 20 to 40%. An antisense oligodeoxynucleotide annealing across the Lab site inhibited initiation at both sites. These and related results lead to the following conclusions. Recruitment by the wild-type IRES is limited by its short oligopyrimidine tract. At least 90% of internal ribosome entry occurs at the Lab AUG, but initiation at this site is restricted by its poor context, despite a counteracting effect of downstream secondary structure. Initiation at the Lb site is by ribosomes that access it by linear scanning from the original entry site, and not by an independent entry process.
Low-pH-Dependent Changes in the Conformation and Oligomeric State of the Prefusion Form of Herpes Simplex Virus Glycoprotein B Are Separable from Fusion Activity
Authors: Dollery Stephen J. , Wright Catherine C. , Johnson David C. , Nicola Anthony V.
Published: August 2011

The cellular requirements for activation of herpesvirus fusion and entry remain poorly understood. Low pH triggers change in the antigenic reactivity of the prefusion form of the herpes simplex virus (HSV) fusion protein gB in virions, both
in vitro
and during viral entry via endocytosis (S. Dollery et al., J. Virol. 84:3759–3766, 2010). However, the mechanism and magnitude of gB conformational change are not clear. Here we show that the conformation and oligomeric state of gB with mutations in the bipartite fusion loops were similarly altered despite the fusion-inactivating mutations. Together with previous studies, this suggests that fusion loop mutants undergo conformational changes but are defective for fusion because they fail to make productive contact with the outer leaflet of the host target membrane. A direct, reversible effect of low pH on the structure of gB was detected by fluorescence spectroscopy. A soluble form of gB containing cytoplasmic tail sequences (s-gB) was triggered by mildly acidic pH to undergo changes in tryptophan fluorescence emission, hydrophobicity, antigenic conformation, and oligomeric structure and thus resembled the prefusion form of gB in the virion. In contrast, soluble gB730, for which the postfusion crystal structure is known, was only marginally affected by pH using these measures. The results underscore the importance of using a prefusion form of gB to assess the activation and extent of conformation change. Further, acidic pH had little to no effect on the conformation or hydrophobicity of gD or on gD's ability to bind nectin-1 or HVEM receptors. Our results support a model in which endosomal low pH serves as a cellular trigger of fusion by activating conformational changes in the fusion protein gB.
Deposition of gold nanoparticles on organo-kaolinite — Application in electrocatalysis for carbon monoxide oxidation
Authors: Letaief Sadok , Pell Wendy , Detellier Christian
Published: August 2011

The clay mineral kaolinite was used as support of gold nanoparticles for heterogeneous catalysis of oxidation reactions, particularly of carbon monoxide oxidation. The application of clay minerals in the preparation of new functional materials provides an alternative approach for the use of these abundant raw materials. To improve the physicochemical properties of kaolinite, as well as to ensure a strong immobilization of the adsorbed species, kaolinite was functionalized by grafting 2-amino-2-methyl-1,3-propanediol on the internal and external surfaces of the octahedral sheets by reaction with the aluminol groups. Gold nanoparticles were then deposited on the external surfaces of the fine particles of the functionalized kaolinite. The resulting gold kaolinite nanohybrid material was characterized by various physicochemical techniques. X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, and energy-dispersive X-ray spectrometry confirmed that gold was effectively reduced to the metallic state during adsorption onto the external surfaces of the modified kaolinite. The gold nanoparticles have a narrow size distribution: more than 88% are less than 4 nm in diameter. Gold nanoparticles deposited on kaolinite catalyze the electro-oxidation of carbon monoxide in alkaline solution at room temperature.
Ginseng aqueous extract attenuates the production of virulence factors, stimulates twitching and adhesion, and eradicates biofilms of Pseudomonas aeruginosa
Authors: Alipour Misagh , Omri Abdelwahab , Suntres Zacharias E.
Published: August 2011

This study was carried out to examine the antimicrobial activity of the aqueous extract of Panax quinquefolius from North American ginseng (NAGE) root against Pseudomonas aeruginosa . The minimum inhibitory concentrations of reference and clinical isolates of Pseudomonas aeruginosa were measured by a standard agar-dilution method. At subinhibitory NAGE concentrations, the secretion of virulence factors, motility on agar, and adhesion to 96-well microplates were studied on the nonmucoid Pseudomonas aeruginosa O1 strain. At suprainhibitory concentrations, the activity of NAGE against mature biofilm complexes formed in the Calgary Biofilm Device and the Stovall flow cell were assessed. NAGE possessed an antibacterial activity against all the Pseudomonas aeruginosa strains at 1.25%–2.5% w/v. NAGE also significantly attenuated pyocyanin, pyoverdine, and lipase concentrations, stimulated twitching, and attenuated swarming and swimming motility. At 1.25% w/v, NAGE augmented adhesion, and at 5% w/v detached 1-day-old biofilms in microplates. The extract also eradicated 6-day-old mature biofilms (5% w/v), and fluorescence microscopy displayed a reduction of live cells and biofilm complexes compared with nontreated biofilms. These data suggest that the aqueous extract from North American ginseng possesses antimicrobial activities in vitro.
COVARIANT RELATIVISTIC DYNAMICS AND THE CONCEPT OF TIME
Authors: LUDWIN D. M. , HORWITZ L. P.
Published: August 2011

The role of time has changed conceptually moving from classical Newtonian physics to general relativity and is one of the main obstacles avoiding a clear unification between a covariant quantum mechanics theory and a theory of gravity. In quantum mechanics as in Newtonian physics, time is an evolutional causal parameter, while in general relativity, time has become a spatial axis where matter is spread over the whole world line (an unlocalized 4D wave function), and the 4D picture became a static picture where our empirical experience of dynamics is merely an illusion of our minds. Understanding that Newtonian time still exists in parallel to the 4D world, raises the possibility to describe gravity within a manifestly covariant quantum theory. The examples of the use of such a theory raise the possibility of a clear interpretation of recent interference in time experiments, and also raise new physics when dealing with a curved spacetime.
With-No-Lysine Kinase 3 (WNK3) stimulates glioma invasion by regulating cell volume
Authors: Haas Brian R. , Cuddapah Vishnu A. , Watkins Stacey , Rohn Katie Jo , Dy Tiffany E. , Sontheimer Harald
Published: August 2011

Among the most prevalent and deadly primary brain tumors, high-grade gliomas evade complete surgical resection by diffuse invasion into surrounding brain parenchyma. Navigating through tight extracellular spaces requires invading glioma cells to alter their shape and volume. Cell volume changes are achieved through transmembrane transport of osmolytes along with obligated water. The sodium-potassium-chloride cotransporter isoform-1 (NKCC1) plays a pivotal role in this process, and previous work has demonstrated that NKCC1 inhibition compromises glioma invasion in vitro and in vivo by interfering with the required cell volume changes. In this study, we show that NKCC1 activity in gliomas requires the With-No-Lysine Kinase-3 (WNK3) kinase. Western blots of patient biopsies and patient-derived cell lines shows prominent expression of Ste-20-related, proline-alanine-rich kinase (SPAK), oxidative stress response kinase (OSR1), and WNK family members 1, 3, and 4. Of these, only WNK3 colocalized and coimmunoprecipitated with NKCC1 upon changes in cell volume. Stable knockdown of WNK3 using specific short hairpin RNA constructs completely abolished NKCC1 activity, as measured by the loss of bumetanide-sensitive cell volume regulation. Consequently, WNK3 knockdown cells showed a reduced ability to invade across Transwell barriers and lacked bumetanide-sensitive migration. This data indicates that WNK3 is an essential regulator of NKCC1 and that WNK3 activates NKCC1-mediated ion transport necessary for cell volume changes associated with cell invasion.
Rhythmic movements are larger and faster but with the same frequency on removal of visual feedback
Authors: Levy-Tzedek S. , Tov M. Ben , Karniel A.
Published: August 2011

The brain controls rhythmic movement through neural circuits combining visual information with proprioceptive information from the limbs. Although rhythmic movements are fundamental to everyday activities the specific details of the responsible control mechanisms remain elusive. We tested 39 young adults who performed flexion/extension movements of the forearm. We provided them with explicit knowledge of the amplitude and the speed of their movements, whereas frequency information was only implicitly available. In a series of 3 experiments, we demonstrate a tighter control of frequency compared with amplitude or speed. We found that in the absence of visual feedback, movements had larger amplitude and higher peak speed while maintaining the same frequency as when visual feedback was available; this was the case even when participants were aware of performing overly large and fast movements. Finally, when participants were asked to modulate continuously movement frequency, but not amplitude, we found the local coefficient of variability of movement frequency to be lower than that of amplitude. We suggest that a misperception of the generated amplitude in the absence of visual feedback, coupled with a highly accurate perception of generated frequency, leads to the performance of larger and faster movements with the same frequency when visual feedback is not available. Relatively low local coefficient of variability of frequency in a task that calls for continuous change in movement frequency suggests that we tend to operate at a constant frequency at the expense of variation in amplitude and peak speed.
PAI-1: An Integrator of Cell Signaling and Migration
Authors: Czekay Ralf-Peter , Wilkins-Port Cynthia E. , Higgins Stephen P. , Freytag Jennifer , Overstreet Jessica M. , Klein R. Matthew , Higgins Craig E. , Samarakoon Rohan , Higgins Paul J.
Published: August 2011

Cellular migration, over simple surfaces or through complex stromal barriers, requires coordination between detachment/re-adhesion cycles, involving structural components of the extracellular matrix and their surface-binding elements (integrins), and the precise regulation of the pericellular proteolytic microenvironment. It is now apparent that several proteases and protease inhibitors, most notably urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1), also interact with several cell surface receptors transducing intracellular signals that significantly affect both motile and proliferative programs. These events appear distinct from the original function of uPA/PAI-1 as modulators of the plasmin-based proteolytic cascade. The multifaceted interactions of PAI-1 with specific matrix components (i.e., vitronectin), the low-density lipoprotein receptor-related protein-1 (LRP1), and the uPA/uPA receptor complex have dramatic consequences on the migratory phenotype and may underlie the pathophysiologic sequalae of PAI-1 deficiency and overexpression. This paper focuses on the increasingly intricate role of PAI-1 as a major mechanistic determinant of the cellular migratory phenotype.
C/EBPα, C/EBPα Oncoproteins, or C/EBPβ Preferentially Bind NF-κB p50 Compared with p65, Focusing Therapeutic Targeting on the C/EBP:p50 Interaction
Authors: Dooher Julia E. , Paz-Priel Ido , Houng Simone , Baldwin Albert S. , Friedman Alan D.
Published: August 2011

Canonical nuclear factor kappaB (NF-κB) activation signals stimulate nuclear translocation of p50:p65, replacing inhibitory p50:p50 with activating complexes on chromatin. C/EBP interaction with p50 homodimers provides an alternative pathway for NF-κB target gene activation, and interaction with p50:p65 may enhance gene activation. We previously found that C/EBPα cooperates with p50, but not p65, to induce Bcl-2 transcription and that C/EBPα induces Nfkb1/p50, but not RelA/p65, transcription. Using p50 and p65 variants containing the FLAG epitope at their N- or C-termini, we now show that C/EBPα, C/EBPα myeloid oncoproteins, or the LAP1, LAP2, or LIP isoforms of C/EBPβ have markedly higher affinity for p50 than for p65. Deletion of the p65 transactivation domain did not increase p65 affinity for C/EBPs, suggesting that unique residues in p50 account for specificity, and clustered mutation of HSDL in the “p50 insert” lacking in p65 weakens interaction. Also, in contrast to Nfkb1 gene deletion, absence of the RelA gene does not reduce Bcl-2 or Cebpa RNA in unstimulated cells or prevent interaction of C/EBPα with the Bcl-2 promoter. Saturating mutagenesis of the C/EBPα basic region identifies R300 and nearby residues, identical in C/EBPβ, as critical for interaction with p50. These findings support the conclusion that C/EBPs activate NF-κB target genes via contact with p50 even in the absence of canonical NF-κB activation and indicate that targeting C/EBP:p50 rather than C/EBP:p65 interaction in the nucleus will prove effective for inflammatory or malignant conditions, alone or synergistically with agents acting in the cytoplasm to reduce canonical NF-κB activation. Mol Cancer Res; 9(10); 1395–405. ©2011 AACR.
Phosphatidylinositol 3-Kinase Inhibitor LY294002 Suppresses Proliferation and Sensitizes Doxorubicin Chemotherapy in Bladder Cancer Cells
Authors: Wu Deyao , Tao Jun , Xu Bin , Qing Weijie , Li Pengchao , Lu Qiang , Zhang Wei
Published: August 2011

Background: Phosphatidylinositol 3-kinase (PI3K)-AKT signaling is a well-characterized pathway involved in the control of cell proliferation, apoptosis and oncogenesis. LY294002 is a commonly used pharmacologic inhibitor which acts at the ATP-binding site of the PI3K enzyme, thus selectively inhibiting the PI3K-AKT nexus. The purpose of the present study was to examine whether PI3K inhibited by LY294002 had an effect on human bladder cancer cells. Methods: After treatment with LY294002, MTT assay, chemosensitivity test, colony formation assay, apoptosis assay and Western blot analysis were conducted in EJ cells. Result: EJ cells treated with LY294002 showed significant AKT phosphorylation suppression in a dose-response manner. Also, PI3K/AKT signaling inhibitor LY294002 suppressed cell proliferation and enhanced the chemosensitivity of doxorubicin in human bladder cancer EJ cells. Furthermore, LY294002 increased cell apoptosis to doxorubicin. Conclusion: The augmentation of doxorubicin with PI3K inhibitor LY294002 may resolve the multidrug resistance of bladder cancer, and this may be a new strategy for achieving tolerance for chemotherapeutic agents in bladder cancer therapy.
Laparoscopic Management of Spontaneous Retroperitoneal Hemorrhage
Authors: Peña Juan A. , Serrano Miriam , Cosentino Marco , Rosales Antonio , Algaba Ferran , Palou Juan , Villavicencio Humberto
Published: August 2011

Wünderlich’s syndrome is a spontaneous nontraumatic massive retroperitoneal hemorrhage. It is usually secondary to a renal neoplasm, with angiomyolipoma being the most frequent followed by renal cell carcinoma. The management of spontaneous retroperitoneal bleeding varies depending on the hemodynamic status of the patient. We present the first report of a transperitoneal laparoscopic nephrectomy in a patient with spontaneous retroperitoneal active bleeding secondary to a right renal mass.
Soft Tissue Cover for an Exposed Transplanted Kidney with a Pedicled Myocutaneous Anterolateral Thigh Perforator and Vastus Lateralis Flap
Authors: Faizal Ali , Bujang Safawi Ehfa , Sundram Murali , Kueh Nai Siong , Normala Basiron
Published: August 2011

Surgical wound infection after a renal transplant procedure can lead to graft loss in the presence of host immunosuppression and graft exposure to the environment. Early cover of the wound with well-vascularized tissue will facilitate early wound healing and preservation of the graft. The pedicle anterolateral thigh perforator flap is a popular flap used for soft tissue reconstruction in the groin and perineum. We present a case of an anterolateral thigh flap used to cover an exposed transplanted kidney after surgical wound breakdown.
Concomitant Carcinoma in situ in Cystectomy Specimens Is Not Associated with Clinical Outcomes after Surgery
Authors: Nuhn Philipp , Bastian Patrick J. , Novara Giacomo , Svatek Robert S. , Karakiewicz Pierre I. , Skinner Eila , Fradet Yves , Izawa Jonathan I. , Kassouf Wassim , Montorsi Francesco , Müller Stefan C. , Fritsche Hans-Martin , Sonpavde Guru , Tilki Derya , Isbarn Hendrik , Ficarra Vincenzo , Dinney Colin P. , Shariat Shahrokh F.
Published: August 2011

Objective: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients. Methods: The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC. Results: 1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups. Conclusions: We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making.
Anaesthesia in Transrectal Prostate Biopsy: Which Is the Most Effective Technique?
Authors: Maccagnano Carmen , Scattoni Vincenzo , Roscigno Marco , Raber Marco , Angiolilli Diego , Montorsi Francesco , Rigatti Patrizio
Published: August 2011

Background: Prostate biopsy (PBx) techniques have changed significantly since the original Hodge’s scheme, with an increase in the number and location of cores. These improvements have been realized in part because of the introduction of different local anaesthesia techniques. We critically analysed the literature discussing the role of anaesthesia techniques for use during PBx to find which technique provides the best pain relief for the patient and safety for the urologist. Methods: We performed a literature review by searching the Medline database for articles published between January 2000 and March 2010. Electronic searches were limited to the keywords ‘transrectal prostate biopsy’ and ‘anaesthesia’. Results: Pain and discomfort perceived during PBx are the result of different anatomic factors: the introduction to and movement of the transrectal ultrasound probe in the rectum and the needle piercing the rectum and the prostate capsule. The anaesthesia techniques currently available can be divided into two groups: local (i.e. intrarectal lubricant agents, periprostatic nerve blocks, caudal blocks, pudendal nerve blocks, and their different combinations) and systemic (i.e. oral/intravenous drug administration and sedoanalgesia). Conclusions: The most effective anaesthesia technique for transrectal PBx performed in outpatient settings is the periprostatic nerve blocks with 1 or 2% lidocaine 10 ml, which is associated with intrarectal lubricant agents, especially in younger people. Nevertheless, the current choice of the anaesthesia technique still depends both on patient characteristics (age, prostate size, number and location of cores, anxious personality, need for re-biopsy) and, above all, the urologist’s experience and habits.
Epidermal Barrier Treatments Based on Vernix Caseosa
Authors: Visscher Marty O. , Barai Namrata , LaRuffa Angela A. , Pickens William L. , Narendran Vivek , Hoath Steven B.
Published: August 2011

Background/Aims: Premature infants lack the vernix caseosa, have an incompetent stratum corneum (SC) barrier and are predisposed to infection. Use of topical agents to improve barrier function has had mixed outcomes. The aim was to determine the effect of vernix versus common barrier creams on the rate and quality of the epidermal barrier repair following controlled wounding. Methods: Minor wounds were created with (1) laser ablation in the minipig and (2) tape stripping of mother’s volar skin as a model for premature skin. Native vernix was applied to the mother’s tape-stripped skin. Treatments were no occlusion (NO), vernix and a petrolatum-based cream (PBC) in the pig, and NO, vernix, PBC, an oil-in-water cream (OWC), a semipermeable film (SP) and full occlusion (FO) in adults. Results: Outcomes for both trials were barrier recovery and skin hydration (moisture accumulation rate, MAT), initial hydration, erythema and dryness in adults. Vernix and PBC produced greater barrier repair than NO in the pig. SP produced greater recovery than NO and FO in adults. Vernix yielded greater recovery than FO and was similar to PBC, OWC and NO. Vernix had a directionally higher MAT than OWC and directionally higher initial hydration than NO. Conclusions: The findings suggest that vernix-based topical creams would be effective for the treatment of epidermal wounds and show promise to augment SC repair and maturation in infants.
Cerebral Gas Embolism from Bronchoscopic Argon Plasma Coagulation: A Case Report
Authors: Shaw Yasmeen , Yoneda Ken Y. , Chan Andrew L.
Published: August 2011

Argon plasma coagulation (APC) is a common and safe bronchoscopic technique used in the management of obstructing lesions and hemorrhage in the central airways. Complications of bronchoscopic APC are uncommon and include hemorrhage, perforation and fire in the airways. While bronchoscopic APC has been reported to cause systemic gas embolization and associated cardiovascular collapse, we report a case of cerebral gas embolization that occurred during bronchoscopic APC and highlight underappreciated potential risk factors for its occurrence.
Helicobacter pylori Upregulates Peripheral Platelet Counts Mainly in Female Patients
Authors: Matsukawa Yoshihiro , Kitamura Noboru , Iwamoto Maho , Kato Kimitoshi , Mizuno Shigeaki , Gon Yasuhiro , Shirinskaya Natalia , Takeuchi Jin , Sawada Shigemasa
Published: August 2011

To evaluate the influence of Helicobacter pylori and sex difference on peripheral platelet counts, dyspeptic patients without immunohaematologic disorders were evaluated. H. pylori infection was verified with the rapid urease test and serum anti-H. pylori IgG antibody. Platelet counts were analysed with a reference to H. pylori infection and sex difference. Among H. pylori-eradicated patients, changes in platelet counts were separately evaluated. Totally, 655 patients were enrolled: 340 patients were infected with H. pylori and 178 patients received eradication therapy, with a success rate of 88.2% (157/178). Females with H. pylori infection definitely manifested elevated platelet counts (infected vs. uninfected 244 ± 57 vs. 219 ± 54 × 109/l; p < 0.0001). H. pylori eradication reduced peripheral platelets by 8 weeks, 5–6 months, 1, 2 and ≧3 years after eradication in females from 248 ± 54 to 237 ± 49, 237 ± 54, 229 ± 48, 238 ± 61 and 232 ± 50 × 109/l (p = 0.0003, 0.0182, 0.0041, 0.0398 and 0.0289), respectively. In males, the reduction was verified by 8 weeks, 1 year and ≧3 years from 226 ± 52 to 217 ± 47, 214 ± 44 and 200 ± 49 × 109/l (p = 0.0464, 0.0164 and 0.0016), respectively. In conclusion, H. pylori infection upregulates platelet counts mainly in females, and eradication reduced peripheral platelets in both sexes. Females appeared more susceptible to H. pylori infection than males with regard to upregulation of platelet counts.
Type I Gastric Carcinoids: A Prospective Study on Endoscopic Management and Recurrence Rate
Authors: Merola Elettra , Sbrozzi-Vanni Andrea , Panzuto Francesco , D’Ambra Giancarlo , Di Giulio Emilio , Pilozzi Emanuela , Capurso Gabriele , Lahner Edith , Bordi Cesare , Annibale Bruno , Delle Fave Gianfranco
Published: August 2011

Background: Type I gastric carcinoids (TIGCs) are neuroendocrine neoplasms arising from enterochromaffin-like cells in atrophic body gastritis. Data regarding their evolution in prospective series are scarce, thus treatment and follow-up are not codified. Our aim was to evaluate clinical outcome and recurrence in TIGCs managed by endoscopic approach. Methods: 33 patients (24 females; median age 65 years, range 23–81) were included and managed through endoscopic follow-up every 6–12 months, with lesion removal and multiple gastric biopsies. Baseline clinical and histological features were analyzed as risk factors by Cox regression. Results: At diagnosis, 7 tumors were intramucosal carcinoids and 26 were polyps (median diameter 5 mm, range 2–20), multiple in 17 patients. Associated severe atrophy was present in 21 cases (63.6%), while mild atrophy was found in 6 cases (18.2%). During a 46-month median follow-up, survival was 100% and no metastases occurred. One patient developed a less-differentiated carcinoid that was radically treated by surgery. 21 patients (63.6%) had recurrence after a median of 8 months, 14 of these (66.6%) had a second recurrence after a median of 8 months following the previous carcinoid removal. Median recurrence-free survival was 24 months. Neither clinical nor biochemical recurrence-predicting factors were found. Conclusions: Although about 60% of TIGCs had recurrence after endoscopic resection, endoscopic management may be considered safe and effective.
Familial Evaluation for Diagnosis of Arrhythmogenic Right Ventricular Dysplasia
Authors: Palmisano Brian T. , Rottman Jeffrey N. , Wells Quinn S. , DiSalvo Thomas G. , Hong Charles C.
Published: August 2011

Most sudden cardiac deaths in young athletes are caused by previously undetected inherited cardiac diseases. Here, we report a case of a young male athlete in whom a presumptive diagnosis of hypertrophic cardiomyopathy (HCM) was made following a near sudden cardiac death. Although his imaging studies initially suggested HCM, a detailed clinical and genetic evaluation of the patient and his asymptomatic father led to the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVD) in both. DNA sequencing revealed that each individual was heterozygous for two rare variants in the PKP2 and DSC2 genes, both of which were previously shown to be associated with ARVD and to encode desmosomal proteins, i.e. the previously reported splicing variant c2489 + 1A>G in the PKP2 gene and the novel p.I109M variant in the DSC2 gene. Imaging and electrophysiologic studies further supported a diagnosis of ARVD in the father. This case highlights the importance of detailed clinical evaluation and genetic testing of family members when dealing with sudden cardiac death or unexplained cardiomyopathies in the young.
Oral Health-Related Quality of Life in Hong Kong Preschool Children
Authors: Wong H.M. , McGrath C.P.J. , King N.M. , Lo E.C.M.
Published: August 2011

Objectives: To assess the impact of early childhood caries (ECC) on the quality of life in a population of preschool children and their families in Hong Kong. Methods: A random sample of 1,296 Chinese preschool children participated in the survey and were subjected to an oral examination for their ECC status by 2 trained examiners. The parents were asked to respond to the Early Childhood Oral Health Impact Scale (ECOHIS) and an extra set of questions concerning their sociodemographic background. Results:The final data analysis included 1,261 children with a mean (±SD) age of 3.9 ± 0.66 years. The prevalence figures for ECC and severe ECC were 19.9 and 15.2%, respectively. Decayed teeth were found in 34.3% of the children while only 5.2% had filled teeth. The mean (±SD) dmft in this group of children was 1.5 ± 2.98. Higher ECOHIS scores were found in parents with lower education or income level, or with children who were born in mainland China (p < 0.05), or with children who had decayed, missing, or filled teeth (p < 0.001). In multiple regression analyses, decayed teeth and filled teeth in primary dentition were the better predictors (p < 0.001) of the ECOHIS score among the various parent and child characteristics collected in this survey. Conclusions: The findings of this study showed that parents of young children with dental caries experience perceived that both the children and other family members had poorer quality of life.
Phase II Study on Weekly Bolus Topotecan in Advanced or Recurrent Cervical Cancer
Authors: Lorusso D. , Mainenti S. , Pietragalla A. , Fusco E. , Malaguti P. , Masciullo V. , Scambia G.
Published: August 2011

Objective: It was the aim of our study to evaluate the efficacy and safety of weekly topotecan in patients with advanced or recurrent cervical disease. Methods: Topotecan was administered intravenously as a weekly infusion at a dose of 3.5 mg/m2 on days 1, 8 and 15 of a 28-day cycle. After the second cycle, the dose was increased to 4 mg/m2 if no grade >2 toxicity occurred. Treatment was continued until disease progression or unacceptable toxicity. Results: Twenty-one patients were enrolled, but only 18 were evaluable for response and toxicity. Ten patients (56%) had received primary surgery + chemoradiation, 6 patients (33%) had previously received surgery + chemotherapy and 2 patients (11%) exclusive chemoradiation. Patients received a mean of 3.5 courses (range 1–6). No complete or partial responses were reported. Two patients (11%) presented disease stabilization as maximum response. Median progression-free survival was 11 weeks (95% CI 15–25), and median overall survival was 28 weeks (95% CI 24–72). The treatment was generally well tolerated. Conclusions: This trial did not report any activity of weekly bolus topotecan in the treatment of advanced or recurrent cervical cancer. Actually, there is no evidence to recommend this therapy in this patient population.