bluuebunny/crossref_metadata_2025 huggingface dataset:
Absence of Poly(ADP-Ribose) Polymerase 1 Delays the Onset of
Salmonella enterica
Serovar Typhimurium-Induced Gut Inflammation
Authors: Altmeyer Matthias , Barthel Manja , Eberhard Matthias , Rehrauer Hubert , Hardt Wolf-Dietrich , Hottiger Michael O.
Published: June 2010

The immune system comprises an innate and an adaptive immune response to combat pathogenic agents. The human enteropathogen
Salmonella enterica
serovar Typhimurium invades the intestinal mucosa and triggers an early innate proinflammatory host gene response, which results in diarrheal disease. Several host factors, including transcription factors and transcription coregulators, are involved in the acute early response to
Salmonella
infection. We found in a mouse model of enterocolitis induced by
S
. Typhimurium that the absence of the nuclear protein poly(ADP-ribose) polymerase 1 (PARP1), a previously described cofactor for NF-κB-mediated proinflammatory gene expression, is associated with a delayed proinflammatory immune response after
Salmonella
infection. Our data reveal that PARP1 is expressed in the proliferative zone of cecum crypts, where it is required for the efficient expression of proinflammatory genes, many of which are related to interferon signaling. Consequently, animals lacking PARP1 show impaired infiltration of immune cells into the gut, with severely delayed inflammation.
Differential Expression of Interleukin-8 by Polymorphonuclear Leukocytes of Two Closely Related Species,Ovis canadensisandOvis aries, in Response toMannheimia haemolyticaInfection
Authors: Herndon Caroline N. , Foreyt William J. , Srikumaran Subramaniam
Published: June 2010

The pneumonic lesions and mortality caused byMannheimia haemolyticain bighorn sheep (BHS;Ovis canadensis) are more severe than those in the related species, domestic sheep (DS;Ovis aries), under both natural and experimental conditions. Leukotoxin (Lkt) and lipopolysaccharide (LPS) are the most important virulence factors of this organism. One hallmark of pathogenesis of pneumonia is the influx of polymorphonuclear leukocytes (PMNs) into the lungs. Lkt-induced cytolysis of PMNs results in the release of cytotoxic compounds capable of damaging lung tissue. Interleukin-8 (IL-8) is a potent PMN chemoattractant. The objective of the present study was to determine if there is differential expression of IL-8 by the macrophages and PMNs of BHS and DS in response toM. haemolytica. Macrophages and PMNs of BHS and DS were stimulated with heat-killedM. haemolyticaor LPS. IL-8 expression by the cells was measured by enzyme-linked immunosorbent assays and real-time reverse transcription-PCR (RT-PCR). The PMNs of BHS expressed severalfold higher levels of IL-8 than those of DS upon stimulation. Lesional lung tissue ofM. haemolytica-infected BHS contained significantly higher levels of IL-8 than nonlesional tissue. The bronchoalveolar lavage (BAL) fluid of infected BHS also contained higher levels of IL-8 than that of infected DS. Depletion of IL-8 reduced migration of PMNs toward BAL fluid by approximately 50%, indicating that IL-8 is integral to PMN recruitment to the lung duringM. haemolyticainfection. Excessive production of IL-8, enhanced recruitment of PMNs, and PMN lysis by Lkt are likely responsible for the severity of the lung lesions inM. haemolytica-infected BHS.
The influenza A (H1N1-2009) experience at the inaugural Asian Youth Games Singapore 2009: mass gathering during a developing pandemic
Authors: Lim Hoon Chin , Cutter Jeffery , Lim Weng Kee , Ee Adrian , Wong Yoong Cheong , Tay Boon Keng
Published: June 2010

From 29 June to 7 July 2009, Singapore hosted the inaugural Asian Youth Games (AYG), which brought 1210 athletes and 810 officials from 43 participating countries. On 11 June, just 1 week before the Games Village Medical Centre started operations, the World Health Organization officially declared a global H1N1 2009 pandemic. Working in close partnership with the Olympic Council of Asia Medical Commission, Singapore AYG Organising Committee and other government agencies, the AYG Medical Services Committee was successful in preventing the local transmission of H1N1, which would have been a threat to the games, as it could have led to the cancellation of these games. This article describes the experience and valuable lessons learnt from managing a sports-related mass gathering during the developing pandemic.
Effects of Ramadan fasting on 60 min of endurance running performance in moderately trained men
Authors: Aziz Abdul Rashid , Wahid Mohamed Faizul , Png Weileen , Jesuvadian Carolyn V
Published: June 2010

Objective

This study examines the effects of Ramadan fasting on endurance performance.

Method

Using a crossover design, 10 moderately trained, active Muslim men performed 60 min runs on a treadmill in the fasted (Ramadan, RAM) and non-fasted (Control, CON) state on two separate counterbalanced occasions. After familiarisation, four subjects performed their CON trial 1 week before Ramadan, while the other six subjects performed their CON trial 1 week after the Ramadan month. The subjects' last meals were standardised before their exercise trials. The 60 min continuous endurance running criteria test consisted of 30 min preloading run at 65% maximum oxygen consumption (Vo2max) intensity speed, followed by another 30 min time trial (TT) where subjects manually adjusted their speeds so as to cover the greatest possible distance.

Results

Subjects ran significantly further during the 30 min TT run in the CON compared to RAM condition (5649±715 vs 5448±847 m, p=0.023). Blood glucose concentration was significantly lower (4.5±0.3 vs 4.9±0.4 mmol/l, p=0.003) and urine specific gravity was significantly higher (1.018±0.006 vs 1.006±0.004, p=0.001) at the start of exercise in the RAM condition than in CON. Physiological responses during the 30 min TT run (mean heart rate, blood lactate and ratings of perceived exertion) were, however, not significantly different between the two conditions (all p>0.05). There were also no significant differences in the subjects' daytime sleepiness or mood profile between the RAM and CON conditions (all p>0.05).

Conclusion

Ramadan fasting has a small yet significant negative impact on endurance running performance, although the impact varies across individuals.
A new 24 h ELISA culture based method forHelicobacter pylorichemosusceptibility
Authors: Perna Federico , Vaira Dino
Published: June 2010

Background

Clarithromycin (CH) and metronidazole (MZ) are routinely used inHelicobacter pyloritreatment regimes. Recently, treatment with these antibiotics has been reported to fail in >30% of patients due to increasing resistance. The common chemosusceptibility methods are cumbersome and take up to 14 days. Chemosusceptibility ofH pyloriis therefore rarely checked.

Aim

To develop a rapid susceptibility test (RST) forH pylori.

Methods

Preliminary experiments were performed to find a broth medium able to support the growth ofH pyloriin 20 h and a reliable detection method to quickly detect the amount ofH pylorigrown in the media. A mixture of different components was the best broth medium; ELISA was chosen as the detection technique. Performance of the new RST was compared to a gold standard (break point agar dilution method). 200 consecutive patients were tested forH pyloriinfection and chemosusceptibility to CH and MZ by the gold standard and RST.

Results

111 patients were infected withH pylori. 105 of these were positive by both RST and the gold standard culture method; 75/105 and 68/105 strains were susceptible to CH and MZ, respectively. RST misdiagnosed 2 strains of CH and 10 strains of MZ.

Conclusions

A new simple and rapid chemosusceptibility test forH pylorihas been validated, which is simple to perform and reduces the procedure time from 6–14 days to 24 h.
A WAVELET-BASED ERROR ESTIMATOR AND AN ADAPTIVE SCHEME FOR PLATE BENDING PROBLEMS
Authors: LI BING , CHEN XUEFENG , HE ZHENGJIA
Published: June 2010

An error estimator based on wavelet coefficients is presented which takes advantage of the property that wavelet coefficients can convey detailed information on the local regularity of a function. Its computational bounds are obtained by means of a wavelet decomposition algorithm. Then, an associated adaptive wavelet finite element method is developed which employs this error estimator for the plate bending problems. Numerical examples are used to assess the accuracy and efficiency of the current error estimator and the adaptive scheme.
MHC-INSPIRED ANTIBODY CLONE ALGORITHM
Authors: ZHANG YU , CHEN XUMING , WU LIHUA , LUO ZIQIANG , LIU XIAOJIE
Published: June 2010

For solving complex optimization problems in some engineering applications, intelligent optimization algorithms based on biological mechanisms have better performance than traditional optimization algorithms. Most of these intelligent algorithms, however, have disadvantages in population diversity and preservation of elitist antibody genes, which lead to the degenerative phenomenon, the zigzag phenomenon, poor global optimization, and low convergence speed. Drawing inspiration from the features of major histocompatibility complex (MHC) in the biological immune system, we propose a novel MHC-inspired antibody clone algorithm (ACAMHC) for solving the above problems. ACAMHC preserves elitist antibody genes through the MHC strings that emulate the MHC haplotype in order to improve its local search capability; it improves the antibody population diversity by gene mutation that mimick the MHC polymorphism to enhance its global search capability. To expand the antibody search space, ACAMHC will add some new random immigrant antibodies with a certain ratio. The convergence of ACAMHC is theoretically proven. The experiments of ACAMHC compared with the canonical clone selection algorithm (CLONALG) on 20 benchmark functions are carried out. The experimental results indicate that the performance of ACAMHC is better than that of CLONALG. The ACAMHC algorithm provides new opportunities for solving previously intractable optimization problems.
DUCTILE FAILURE SIMULATION IN SPHERODIZED STEEL USING A CONTINUUM DAMAGE MECHANICS COUPLED FINITE ELEMENT FORMULATION
Authors: GAUTAM SACHIN S. , DIXIT P. M.
Published: June 2010

Ductile fracture occurs due to microvoid nucleation, growth and, finally, coalescence into microcracks. These microcracks grow in the presence of stresses leading to fracture. In this work, a criterion based on this phenomenon is used to simulate ductile fracture in a class of steel specimens. A critical value of the damage variable, estimated from experimental results, is used as an indicator of fracture initiation. A continuum damage mechanics model is employed to incorporate the damage in the constitutive relation of the material. A damage growth law based on experimental results is used. It is observed that the damage reaches the critical value first at the center in both the cylindrical and prenotched specimens. Thus, the failure begins at the center and then grows radially outward toward the free surface. The analysis is carried out till the damage reaches the critical value across the whole cross-section, at which point the specimen is considered to have failed.
NUMERICAL SIMULATION OF FLUID FLOW AND HEAT TRANSFER DURING THE INITIAL PHASE LEADING TO STEADY STATE SOLIDIFICATION IN D. C. CAST ALUMINUM ALLOYS
Authors: KORTI ABDEL ILLAH NABIL
Published: June 2010

In this paper, two dimensional unsteady flow and energy equations are employed for simulating the fluid flow, heat transfer and solidification during direct chill continuous casting of Al-Mg alloy billet. In these processes, the formation of some macro defects such as thermal cracking, hot tearing, surface cracking, etc, has been found to initiate during the starting phase of the operation. In this paper, a numerical study of these developing fluid flow and thermal phenomena from the beginning of casting operation to a steady-state is presented. The computations are based on an iterative deforming finite volume method and a single-domain enthalpy formulation to solve the growth of metal being solidified and the accompanying dynamic fluid flow and thermal behavior. The effect of phase change on convection is accounted for using a Darcy's law-type porous media treatment. The results indicate that the fluid flow and temperature fields change drastically at the initial stage but evolve slowly afterwards.
KAMISHIBAI KEYGRAPH: TOOL FOR VISUALIZING STRUCTURAL TRANSITIONS FOR DETECTING TRANSIENT CAUSES
Authors: OHSAWA YUKIO , ITO TAKAICHI , KAMATA MAYMI I.
Published: June 2010

The causes of risks are hard to identify if events occur temporarily and disappear before the occurrence of their observable effects. In the face of this hurdle, transient causal events of significant effects are desired to be explained, for the safety of human life. In this paper, Kamishibai KeyGraph, a variation of KeyGraph developed to deal with sequential data, is presented as a tool to explain the causality involving transient causes. This method is applied here for two data sets: (1) newspaper text on social events, and (2) data on earthquakes in Japan. The performance of this method is hard to evaluate quantitatively due to the nature of transient events, so we partially evaluate the qualitative scenarios interpreted subjectively from the visualized maps.
VISUAL ANALYSIS OF DISCUSSION FLOW ON KEYGRAPH-BASED BBS
Authors: TAKAMA YASUFUMI , KOINUMA GAKU
Published: June 2010

A method for visualizing discussion flow is proposed for analyzing the thread in KGBBS (KeyGraph-based BBS). It is known that group discussion is effective for chance discovery, in which information visualization plays an important role in providing participants with a material to that brainstorm various ideas, opinions, and interpretations. In order to enable online discussion while sharing the same visualized material, KGBBS is proposed based on KeyGraph, which is one of the typical visualization techniques in chance discovery. The aim of this paper is to utilize the result of discussion using KGBBS, by visualizing discussion flow of the thread in KGBBS. The method consists of 2 kinds of visualization techniques — a comment chain diagram to visualize the structure of comment chain, and a visual summary on KeyGraph to visualize concrete transition of topics through successive 2 or 3 comments. The proposed method is applied to actual discussion data, and the analysis results show the combination of both the visualization techniques, making it possible to analyze concrete transition of topics without reading comments in a thread.
MODELING THE DEGREE OF TRUTHFULNESS
Authors: WANG PAUL P. , HSIEH CHIH HSUN
Published: June 2010

This paper reports some novel approach on linguistic logic with our intention to realize CWW, Computing With Words, via a simple example which consists of only five words. As a by product, this simple example of the linguistic logical system may serve as a mathematical model, modeling the degree of truthfulness in daily usage. The five words set of a linguistic variable modeling the degree of truthfulness are; true, nearly true, undecided, nearly false and false. We subjectively choose trapezoidal fuzzy numbers as our linguistic truth values in order to model our linguistic logic system. Firstly, some natural operations and linguistic logic operators are defined to suit our objective of developing a closed linguistic variable set. Then the computation of linguistic truth values for this linguistic logical system is developed in order to facilitate us to perform the linguistic inferences. Properties of these natural operations can be derived accordingly. It is perhaps quite rewarding to see numerous linguistic truth relations defined on a single linguistic truth set and linguistic implications ended up with numerous linguistic truth tables. In addition, the linguistic inferences of generalized modus ponens and generalized tollens determined by linguistic compositional rules based on the linguistic truth relation and some natural operations are introduced. The simple examples of the linguistic inferences of the various generalized tautologies are illustrated. Finally, we have proved via a simple dictionary that a closed and self consistent linguistic logical system indeed can be constructed and it is possible to move a chunk of information as modeled by a fuzzy set to a higher level according to the theory of semiotics. These results have shown some promise in realizing the appealing theory of CWW.
Upper Triassic–lowermost Jurassic palynology and palynostratigraphy: a review
Authors: Cirilli Simonetta
Published: June 2010

This review advances understanding of the palynostratigraphy of the Late Triassic–Early Jurassic by correlating the established palynozonations for the northern and southern hemispheres. Previous palynological studies have contributed greatly to our understanding of the biostratigraphy, paleoclimatology and paleogeography of the Upper Triassic. In general, palynology is a good tool for interregional cross-correlation of marine and non-marine successions because palynomorphs, unlike most of other fossils, commonly are present in continental and marine environments. Currently, however, biostratigraphical resolution based on Upper Triassic palynomorph assemblages is rather low, primarily because of the rarity of successions that are independently dated (i.e. via ammonoids, conodonts, isotopes, paleomagnetism) to correlate the palynomorph assemblages, but also for other reasons, such as microfloristic provincialism, palaeoenvironmental conditions and differential preservation of palynomorph assemblages. During the last few decades many palynological studies have attempted to integrate and improve the biostratigraphical correlations and paleoclimatologic reconstructions across the Triassic–Jurassic boundary. Several authors have recognized specific microfloral assemblages with well-defined and recognizable suites of palynomorphs that enhance the importance of palynomorphs in the definition of Triassic–Jurassic stages. Comparison of the palynomorph assemblages from different biostratigraphical stages demonstrates that a change occurred in the palynofloral composition of the Tethyan domain between the Carnian and the earliest Hettangian that was gradual and without abrupt changes.
The Triassic timescale based on nonmarine tetrapod biostratigraphy and biochronology
Authors: Lucas Spencer G.
Published: June 2010

The Triassic timescale based on nonmarine tetrapod biostratigraphy and biochronology divides Triassic time into eight land-vertebrate faunachrons (LVFs) with boundaries defined by the first appearance datums (FADs) of tetrapod genera or, in two cases, the FADs of a tetrapod species. Definition and characterization of these LVFs is updated here as follows: the beginning of the Lootsbergian LVF=FAD ofLystrosaurus; the beginning of the Nonesian=FADCynognathus; the beginning of the Perovkan LVF=FADEocyclotosaurus; the beginning of the Berdyankian LVF=FADMastodonsaurus giganteus; the beginning of the Otischalkian LVF=FADParasuchus; the beginning of the Adamanian LVF=FADRutiodon; the beginning of the Revueltian LVF=FADTypothorax coccinarum; and the beginning of the Apachean LVF=FADRedondasaurus. The end of the Apachean (= beginning of the Wasonian LVF, near the beginning of the Jurassic) is the FAD of the crocodylomorphProtosuchus. The Early Triassic tetrapod LVFs, Lootsbergian and Nonesian, have characteristic tetrapod assemblages in the Karoo basin of South Africa, theLystrosaurusassemblage zone and the lower two-thirds of theCynognathusassemblage zone, respectively. The Middle Triassic LVFs, Perovkan and Berdyankian, have characteristic assemblages from the Russian Ural foreland basin, the tetrapod assemblages of the Donguz and the Bukobay svitas, respectively. The Late Triassic LVFs, Otischalkian, Adamanian, Revueltian and Apachean, have characteristic assemblages in the Chinle basin of the western USA, the tetrapod assemblages of the Colorado City Formation of Texas, Blue Mesa Member of the Petrified Forest Formation in Arizona, and Bull Canyon and Redonda formations in New Mexico. Since the Triassic LVFs were introduced, several subdivisions have been proposed: Lootsbergian can be divided into three sub-LVFs, Nonesian into two, Adamanian into two and Revueltian into three. However, successful inter-regional correlation of most of these sub-LVFs remains to be demonstrated. Occasional records of nonmarine Triassic tetrapods in marine strata, palynostratigraphy, conchostracan biostratigraphy, magnetostratigraphy and radioisotopic ages provide some basis for correlation of the LVFs to the standard global chronostratigraphic scale. These data indicate that Lootsbergian=uppermost Changshingian, Induan and possibly earliest Olenekian; Nonesian=much of the Olenekian; Perovkan=most of the Anisian; Berdyankian=latest Anisian? and Ladinian; Otischalkian=early to late Carnian; Adamanian=most of the late Carnian; Revueltian=early–middle Norian; and Apachean=late Norian–Rhaetian. The Triassic timescale based on tetrapod biostratigraphy and biochronology remains a robust tool for the correlation of nonmarine Triassic tetrapod assemblages independent of the marine timescale.
Triassic conodonts and their role in stage boundary definition
Authors: Orchard Michael J.
Published: June 2010

Conodonts have played an important role in the construction of a Triassic timescale. Each of the stage boundaries is reviewed in the context of their evolving conodont faunas. The base Triassic (Induan) is defined by the appearance of
Hindeodus parvus
, which developed from
H. praeparvus
; a parallel zonation is provided by
Neogondolella
species. For the Induan–Olenekian boundary, the appearance of
Neospathodus waageni sensu lato
within a plexus of similar species is favoured as the defining datum;
Borinella
and
Eurygnathodus
also appear about this time. The base of the Middle Triassic Anisian stage lies close to the appearance of
Chiosella
, with
Triassospathodus
and
Spathicuspus
characterizing the late Olenekian, and
Gladigondolella tethydis
and
Nicoraella
confined to the Anisian. Proxies for the Anisian–Ladinian boundary, which is defined by an ammonoid, are the first
Budurovignathus
species. The basal Carnian, also defined by an ammonoid, lies close to the first metapolygnathids, including
M. polygnathiformis
and
M. tadpole
. The Carnian–Norian boundary interval is characterized by many new taxa in Canada, but only a few species are common to Tethys, notably
Metapolygnathus
ex gr.
M. echinatus
. The Norian–Rhaetian boundary is likely to be based on evolution in
Misikella
in Tethys, with concurrent changes recognized in North American
Epigondolella
.
Triassic radiolarian biostratigraphy
Authors: O'Dogherty Luis , Carter Elizabeth S. , Goričan Špela , Dumitrica Paulian
Published: June 2010

This paper summarizes 30 years of research on the biostratigraphy of Triassic radiolarians and presents a correlation of currently-used radiolarian zonations established in North America, Europe, Japan and Far East Russia. An up-to-date stratigraphic distribution of all hitherto described and still valid Triassic genera is provided. This new range chart consists of 282 genera and allows an accurate dating to substage level. It also clearly manifests general trends in radiolarian evolution through the Triassic. The end-Permian extinction, the most severe extinction in the history of radiolarians, was followed by a long recovery until the early Anisian. The middle and late Anisian were then characterized by a rapid explosion of new morphologies. Maximum generic diversity was attained during the early Carnian, but the first severe extinctions also occurred in the Carnian. A progressive decline of diversity took place through the Norian and Rhaetian, and ended in a mass extinction around the Triassic–Jurassic boundary.
BogusBiter
Authors: Yue Chuan , Wang Haining
Published: June 2010

Many anti-phishing mechanisms currently focus on helping users verify whether a Web site is genuine. However, usability studies have demonstrated that prevention-based approaches alone fail to effectively suppress phishing attacks and protect Internet users from revealing their credentials to phishing sites. In this paper, instead of preventing human users from “biting the bait,” we propose a new approach to protect against phishing attacks with “bogus bites.” We developBogusBiter, a unique client-side anti-phishing tool, which transparently feeds a relatively large number of bogus credentials into a suspected phishing site. BogusBiter conceals a victim's real credential among bogus credentials, and moreover, it enables a legitimate Web site to identify stolen credentials in a timely manner. Leveraging the power of client-side automatic phishing detection techniques, BogusBiter is complementary to existing preventive anti-phishing approaches. We implemented BogusBiter as an extension to the Firefox 2 Web browser, and evaluated its efficacy through real experiments on both phishing and legitimate Web sites. Our experimental results indicate that it is promising to use BogusBiter to transparently protect against phishing attacks.
Teaching Johnny not to fall for phish
Authors: Kumaraguru Ponnurangam , Sheng Steve , Acquisti Alessandro , Cranor Lorrie Faith , Hong Jason
Published: June 2010

Phishing attacks, in which criminals lure Internet users to Web sites that spoof legitimate Web sites, are occurring with increasing frequency and are causing considerable harm to victims. While a great deal of effort has been devoted to solving the phishing problem by prevention and detection of phishing emails and phishing Web sites, little research has been done in the area of training users to recognize those attacks. Our research focuses on educating users about phishing and helping them make better trust decisions. We identified a number of challenges for end-user security education in general and anti-phishing education in particular: users are not motivated to learn about security; for most users, security is a secondary task; it is difficult to teach people to identify security threats without also increasing their tendency to misjudge nonthreats as threats. Keeping these challenges in mind, we developed an email-based anti-phishing education system called “PhishGuru” and an online game called “Anti-Phishing Phil” that teaches users how to use cues in URLs to avoid falling for phishing attacks. We applied learning science instructional principles in the design of PhishGuru and Anti-Phishing Phil. In this article we present the results of PhishGuru and Anti-Phishing Phil user studies that demonstrate the effectiveness of these tools. Our results suggest that, while automated detection systems should be used as the first line of defense against phishing attacks, user education offers a complementary approach to help people better recognize fraudulent emails and websites.
Metal Nanoparticles and Carbon-Based Nanostructures as Advanced Materials for Cathode Application in Dye-Sensitized Solar Cells
Authors: Calandra Pietro , Calogero Giuseppe , Sinopoli Alessandro , Gucciardi Pietro Giuseppe
Published: June 2010

We review the most advanced methods for the fabrication of cathodes for dye-sensitized solar cells employing nanostructured materials. The attention is focused on metal nanoparticles and nanostructured carbon, among which nanotubes and graphene, whose good catalytic properties make them ideal for the development of counter electrode substrates, transparent conducting oxide, and advanced catalyst materials.
Piperacillin-Induced Immune Hemolytic Anemia in an Adult with Cystic Fibrosis
Authors: Bandara Mahesh , Seder David B. , Garratty George , Leger Regina M. , Zuckerman Jonathan B.
Published: June 2010

We report a case of drug-induced immune hemolytic anemia (DIIHA) in an adult female with cystic fibrosis (CF), complicating routine treatment of a pulmonary exacerbation with intravenous piperacillin-tazobactam. Workup revealed a positive direct antiglobulin test (DAT) due to red blood cell (RBC)-bound IgG and C3 and piperacillin antibodies detectable in the patient's serum. The potential influence of CF transmembrane conductance regulator mutations on the severity of DIIHA is discussed. This report illustrates the importance of early identification of DIIHA, a rare complication of a commonly utilized medication in CF.
Synthesis and Characterization of Novel Ruthenium(III) Complexes with Histamine
Authors: Kljun Jakob , Petriček Saša , Žigon Dušan , Hudej Rosana , Miklavčič Damijan , Turel Iztok
Published: June 2010

Novel ruthenium(III) complexes with histamine (1a) and [RuCl4(dmso‐S)(histamineH)] (1b) have been prepared and characterized by X‐ray structure analysis. Their crystal structures are similar and show a protonated amino group on the side chain of the ligand which is not very common for a simple heterocyclic derivative such as histamine. Biological assays to test the cytotoxicity of the compound 1b combined with electroporation were performed to determine its potential for future medical applications in cancer treatment.
Developmental Stage-Specific Imprinting ofIPLin Domestic Pigs (Sus scrofa)
Authors: Hou Shengping , Chen Yuming , Liang Jie , Li Li , Wu Tongshan , Tian X. Cindy , Zhang Shouquan
Published: June 2010

Imprinted in placenta and liver (IPL) gene has been identified as an imprinted gene in the mouse and human. Its sequence and imprinting status, however, have not been determined in the domestic pigs. In the present study, a 259 base pair-specific sequence forIPLgene of the domestic pig was obtained and a novel SNP, a T/C transition, was identified inIPLexon 1. The C allele of this polymorphism was found to be the predominant allele in Landrace,Yorkshire, and Duroc. The frequency of CC genotype and C allele are different in Duroc as compared with Yorkshire (P=.038andP=.005, resp.). Variable imprinting status of this gene was observed in different developmental stages. For example, it is imprinted in 1-dayold newborns (expressed from the maternal allele), but imprinting was lost in 180-day-old adult (expressed from both parental alleles). Real-time PCR analysis showed the porcineIPLgene is expressed in all tested eight organ/tissues. The expression level was significantly higher in spleen, duodenum, lung, and bladder of 180-day-old Lantang adult compared to that in 1-day-old newborns Lantang pigs (P<.05). In conclusion, the imprinting of the porcineIPLgene is developmental stage and tissue specific.
Involvement of Nitric Oxide in a Rat Model of Carrageenin-Induced Pleurisy
Authors: Iwata Masahiro , Suzuki Shigeyuki , Asai Yuji , Inoue Takayuki , Takagi Kenji
Published: June 2010

Some evidence indicates that nitric oxide (NO) contributes to inflammation, while other evidence supports the opposite conclusion. To clarify the role of NO in inflammation, we studied carrageenin-induced pleurisy in rats treated with an NO donor (NOC-18), a substrate for NO formation (L-arginine), and/or an NO synthase inhibitor (S-(2-aminoethyl) isothiourea or -nitro-L-arginine). We assessed inflammatory cell migration, nitrite/nitrate values, lipid peroxidation and pro-inflammatory mediators. NOC-18 and L-arginine reduced the migration of inflammatory cells and edema, lowered oxidative stress, and normalized antioxidant enzyme activities. NO synthase inhibitors increased the exudate formation and inflammatory cell number, contributed to oxidative stress, induced an oxidant/antioxidant imbalance by maintaining high , and enhanced the production of pro-inflammatory mediators. L-arginine and NOC-18 reversed the proinflammatory effects of NO synthase inhibitors, perhaps by reducing the expression of adhesion molecules on endothelial cells. Thus, our results indicate that NO is involved in blunting—not enhancing—the inflammatory response.
Symptomatic Hypoglycemia Related to Inappropriately High IGF-II Serum Levels in a Patient with Desmoplastic Small Round Cell Tumor
Authors: Barra Williams Fernandes , Castro Gilberto , Hoff Ana Oliveira , Siqueira Sheila A. C. , Hoff Paulo M.
Published: June 2010

A 45-year old man was diagnosed with desmoplastic small round cell tumor (DSRCT) with involvement of the peritoneum and pelvis. Disease progression was observed despite systemic chemotherapy. Six months after diagnosis, he developed severe hypoglycemia presented with seizures. He received intravenous glucose infusion and hydrocortisone with poor glycemic control, but with seizures resolution. The investigation excluded insulinoma, adrenal, liver and GH deficiencies. Laboratory showed slight rise of IGF-II and significant increase of the ratio IGF-II : IGF-I, which is pathognomonic ofnon-islet cell tumor hypoglycemia(NICTH). He received the diagnoses of NICTH related to IGF-II inappropriate production by DSRCT. Despite the attempt to control tumor mass and hypoglycemia, the patient died 9 months after diagnosis. NICTH related to inappropriate IGF-II secretion should be investigated in all cancer patients with refractory hypoglycemia whom insulinoma and other metabolic abnormalities were excluded from.
Combination of Intensive Chemotherapy and Anticancer Vaccines in the Treatment of Human Malignancies: The Hematological Experience
Authors: Liseth Knut , Ersvær Elisabeth , Hervig Tor , Bruserud Øystein
Published: June 2010

In vitro studies have demonstrated that cancer-specific T cell cytotoxicity can be induced both ex vivo and in vivo, but this therapeutic strategy should probably be used as an integrated part of a cancer treatment regimen. Initial chemotherapy should be administered to reduce the cancer cell burden and disease-induced immune defects. This could be followed by autologous stem cell transplantation that is a safe procedure including both high-dose disease-directed chemotherapy and the possibility for ex vivo enrichment of the immunocompetent graft cells. The most intensive conventional chemotherapy and stem cell transplantation are used especially in the treatment of aggressive hematologic malignancies; both strategies induce T cell defects that may last for several months but cancer-specific T cell reactivity is maintained after both procedures. Enhancement of anticancer T cell cytotoxicity is possible but posttransplant vaccination therapy should probably be combined with optimalisation of immunoregulatory networks. Such combinatory regimens should be suitable for patients with aggressive hematological malignancies and probably also for other cancer patients.
Nanocrystalline Pb(Zr0.52Ti0.48)O3 Ferroelectric Ceramics: Mechanical and Electrical Properties
Authors: Ramana M. Venkata , Reddy M. Penchal , Reddy N. Ramamanohar , Kumar K. V. Siva , Murthy V. R. K. , Murty B. S.
Published: June 2010

Nanocrystalline powders of the composition Pb(Zr0.52Ti0.48)O3 were obtained by Mechanical alloying (high‐energy ball milling). X‐ray diffraction studies show that these compounds are completely into the perovskite phase. Detailed studies of electrical and mechanical properties of PZT as a function of temperature (and frequency) showed the high permittivity of 20653 at Curie transition temperature. Temperature variation of longitudinal modulus and internal friction of these ceramics at 104 kHz frequency were studied in the wide temperature range of 30∘C–420∘C. The internal friction measurements showed sharp stress induced relaxation peaks in the present composition corresponding to those temperatures where the minima were noticed in temperature variation of longitudinal modulus behavior. This dielectric and internal friction behaviour was explained in the light of polaron hopping mechanism and structural phase transitions in the present piezoelectric compositions.
Hypomethylation ofIL10andIL13Promoters in CD4+T Cells of Patients with Systemic Lupus Erythematosus
Authors: Zhao Ming , Tang Jinling , Gao Fei , Wu Xiaoyan , Liang Yunsheng , Yin Heng , Lu Qianjin
Published: June 2010

Interleukin- (IL-)10 and IL-13 play important roles in Th2 cell differentiation and production of autoantibodies in patients with (SLE). However, the mechanisms leading toIL10andIL13overexpression in SLE patients are not well understood. In this study, we confirm that the levels of bothIL10andIL13mRNA in CD4+T cells and of serumIL10andIL13proteins are increased in SLE patients. We show that the DNA methylation levels withinIL10andIL13gene regulatory domains are reduced in SLE CD4+T cells relative to healthy controls and negatively correlate withIL10andIL13mRNA expression. Moreover, treating healthy CD4+T cells with the demethylating agent 5-azacytidine (5-azaC) increasedIL10andIL13mRNA transcription. Together, our results show that promoter methylation is a determinant ofIL10andIL13expression in CD4+T cells, and we propose that DNA hypomethylation leads toIL10andIL13overexpression in SLE patients.
Atoh1 Inhibits Neuronal Differentiation and Collaborates with Gli1 to Generate Medulloblastoma-Initiating Cells
Authors: Ayrault Olivier , Zhao Haotian , Zindy Frederique , Qu Chunxu , Sherr Charles J. , Roussel Martine F.
Published: June 2010

The morphogen and mitogen Sonic Hedgehog (Shh) activates a Gli1-dependent transcription program that drives proliferation of granule neuron progenitors (GNP) within the external germinal layer of the postnatally developing cerebellum. Medulloblastomas with mutations activating the Shh signaling pathway preferentially arise within the external germinal layer, and the tumor cells closely resemble GNPs. Atoh1/Math1, a basic helix-loop-helix transcription factor essential for GNP histogenesis, does not induce medulloblastomas when expressed in primary mouse GNPs that are explanted from the early postnatal cerebellum and transplanted back into the brains of naïve mice. However, enforced expression of Atoh1 in primary GNPs enhances the oncogenicity of cells overexpressing Gli1 by almost three orders of magnitude. Unlike Gli1, Atoh1 cannot support GNP proliferation in the absence of Shh signaling and does not govern expression of canonical cell cycle genes. Instead, Atoh1 maintains GNPs in a Shh-responsive state by regulating genes that trigger neuronal differentiation, including many expressed in response to bone morphogenic protein-4. Therefore, by targeting multiple genes regulating the differentiation state of GNPs, Atoh1 collaborates with the pro-proliferative Gli1-dependent transcriptional program to influence medulloblastoma development. Cancer Res; 70(13); 5618–27. ©2010 AACR.
Calcium Intake Increases Risk of Prostate Cancer among Singapore Chinese
Authors: Butler Lesley M. , Wong Alvin S. , Koh Woon-Puay , Wang Renwei , Yuan Jian-Min , Yu Mimi C.
Published: June 2010

Consumption of dairy products, the primary source of calcium in Western diets, has been found to be positively associated with prostate cancer. In an Asian diet, nondairy foods are the major contributors of calcium. Thus, a study of dietary calcium and prostate cancer in Asians can better inform on whether calcium, as opposed to other dairy components, is responsible for the dairy foods–prostate cancer association. We examined calcium intake and prostate cancer risk among 27,293 men in the Singapore Chinese Health Study that was established between 1993 and 1998. As of December 31, 2007, 298 incident prostate cancer cases had been diagnosed among the cohort members. Diet was assessed at baseline with a validated 165-item food-frequency questionnaire. It is hypothesized that there is greater net absorption of calcium in smaller individuals. Therefore, the calcium–prostate cancer association was also assessed in stratified analyses by median body mass index. Vegetables were the largest contributor of daily calcium intake in the study population. Overall, we observed a modest, statistically nonsignificant 25% increase in prostate cancer risk for the 4th (median = 659 mg/d) versus 1st (median = 211 mg/d) quartiles of calcium intake after adjustment for potential confounders. The association became considerably stronger and achieved statistical significance (hazard ratio, 2.03; 95% confidence interval, 1.23–3.34; P for trend = 0.01) for men with a below median body mass index (22.9 kg/m2). Dietary calcium might be a risk factor for prostate cancer even at relatively low intake. Cancer Res; 70(12); 4941–8. ©2010 AACR.
Interaction between Adiponectin and Leptin Influences the Risk of Colorectal Adenoma
Authors: Yamaji Taiki , Iwasaki Motoki , Sasazuki Shizuka , Tsugane Shoichiro
Published: June 2010

Obesity has been associated with an increased risk of colorectal neoplasia, but the mechanisms of this potential association have not been elucidated. We hypothesized that the adipokines adiponectin, leptin, and tumor necrosis factor-α (TNF-α) may mediate an association between obesity and colorectal cancer. We measured plasma concentrations of total and high-molecular-weight (HMW) adiponectin, leptin, and TNF-α in healthy volunteer examinees who underwent total colonoscopy between February 2004 and February 2005, and conducted a case-control study consisting of 778 cases and 735 controls. An inverse association of total and HMW adiponectin was observed with colorectal adenoma (P trend < 0.001 and 0.03, respectively). Further, total adiponectin interacted with leptin, but not TNF-α, in relation to colorectal adenoma (P interaction = 0.007). An inverse association of total adiponectin with colorectal adenoma was apparent in the highest two tertiles of leptin, particularly the middle (P trend < 0.001), whereas a positive association of leptin was obvious in the lowest tertile of total adiponectin (P trend = 0.01) after adjusting for potential confounders and body mass index, which is a major determinant of insulin resistance. Adiponectin may exert an anticarcinogenic effect on the large intestine by interfering with leptin, whereas leptin could conversely exert a carcinogenic effect under conditions of a lower abundance of adiponectin. Our findings provide the first epidemiologic evidence for interactive effects of adiponectin and leptin in the early stage of colorectal tumorigenesis, distinct from their involvement in insulin resistance. Cancer Res; 70(13); 5430–7. ©2010 AACR.
Complement Factor H Autoantibodies Are Associated with Early Stage NSCLC
Authors: Amornsiripanitch Nita , Hong Shaolin , Campa Michael J. , Frank Michael M. , Gottlin Elizabeth B. , Patz Edward F.
Published: June 2010

Purpose: To discover diagnostic biomarkers associated with early-stage non–small cell lung cancer (NSCLC), we searched for autoantibodies preferentially present in stage I patients compared with patients with advanced-stage disease. Here we describe an autoantibody against complement factor H (CFH) and this autoantibody's association with early-stage NSCLC.

Experimental Design: Immunoblots were used to detect autoantibodies in the sera of stage I NSCLC patients. An autoantibody recognizing a 150 kDa protein was discovered, and the protein was identified by mass spectrometry. The association of the autoantibody with early-stage disease was suggested by the results of immunoblot analysis with sera from 28 stage I patients and 28 stage III/IV patients. This association was confirmed by protein microarray of sera from 125 NSCLC patients of all stages as well as 125 controls matched by age, gender, and smoking history.

Results: The immunoreactive protein was identified as CFH. By immunoblot analysis, anti-CFH autoantibody was found in 50% of stage I NSCLC patients and 11% of late-stage NSCLC patients (P = 0.003). By protein microarray analysis, patients with stage I NSCLC had a significantly higher incidence of anti-CFH antibody than those with late-stage NSCLC (P = 0.0051). The percentage of sera with a positive level of CFH autoantibody was 30.4% in stage I, 21.1% in stage II, 12.5% in stage III, 7.4% in stage IV, and 8.0% in the control group.

Conclusions: These findings suggest that in patients with NSCLC, CFH autoantibody is a molecular marker associated with early-stage disease. Clin Cancer Res; 16(12); 3226–31. ©2010 AACR.
Butein Sensitizes Human Hepatoma Cells to TRAIL-Induced Apoptosis via Extracellular Signal-Regulated Kinase/Sp1–Dependent DR5 Upregulation and NF-κB Inactivation
Authors: Moon Dong-Oh , Kim Mun-Ock , Choi Yung Hyun , Kim Gi-Young
Published: June 2010

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces cell death in various types of cancer cells but has little or no effect on normal cells. Human hepatoma cells are resistant to TRAIL-induced apoptosis. Although butein is known to mediate anticancer, anti-inflammatory, and antioxidant activities, little is known about the mechanism of butein in terms of TRAIL-induced apoptosis of human hepatoma cells. In this study, we determined that butein enhances TRAIL-induced apoptosis in hepatoma cells through upregulation of DR5. Luciferase analysis showed that a 5′-flanking region containing four Sp1-binding sites within the DR5 promoter was enhanced by butein (−305/−300). Electrophoretic mobility shift assays and chromatin immunoprecipitation studies were used to analyze the elevation of Sp1 binding to DR5 promoter sites by butein. Point mutations of the Sp1-binding site also attenuated promoter activity. Furthermore, pretreatment of the blocking chimeric antibody and small interfering RNA for DR5 significantly suppressed TRAIL-mediated apoptosis by butein in Hep3B cells. Butein also stimulated extracellular signal-regulated kinase (ERK) activation, and the ERK inhibitor PD98059 blocked butein-induced DR5 expression and suppressed binding of Sp1 to the DR5 promoter. Additionally, generation of reactive oxygen species had no effect on cell viability, although pretreatment with N-acetyl-l-cysteine or glutathione inhibited combined treatment-induced reactive oxygen species. Indeed, butein repressed the TRAIL-mediated activation of NF-κB and decreased its transcriptional activity. Our results suggest that butein could sensitize certain human hepatoma cells to TRAIL-induced apoptosis through stimulating its death signaling and by repressing the survival function in these cells. Mol Cancer Ther; 9(6); 1583–95. ©2010 AACR.
A Human Monoclonal Antibody against Insulin-Like Growth Factor-II Blocks the Growth of Human Hepatocellular Carcinoma Cell Lines In vitro and In vivo
Authors: Dransfield Daniel T. , Cohen Edward H. , Chang Qing , Sparrow Lindsay G. , Bentley John D. , Dolezal Olan , Xiao Xiaowen , Peat Thomas S. , Newman Janet , Pilling Patricia A. , Phan Tram , Priebe Ilka , Brierley Gemma V. , Kastrapeli Niksa , Kopacz Kris , Martik Diana , Wassaf Dina , Rank Douglas , Conley Greg , Huang Yan , Adams Timothy E. , Cosgrove Leah
Published: June 2010

Elevated expression of insulin-like growth factor-II (IGF-II) is frequently observed in a variety of human malignancies, including breast, colon, and liver cancer. As IGF-II can deliver a mitogenic signal through both IGF-IR and an alternately spliced form of the insulin receptor (IR-A), neutralizing the biological activity of this growth factor directly is a potential alternative option to IGF-IR–directed agents. Using a Fab-displaying phage library and a biotinylated precursor form of IGF-II (1–104 amino acids) as a target, we isolated Fabs specific for the E-domain COOH-terminal extension form of IGF-II and for mature IGF-II. One of these Fabs that bound to both forms of IGF-II was reformatted into a full-length IgG, expressed, purified, and subjected to further analysis. This antibody (DX-2647) displayed a very high affinity for IGF-II/IGF-IIE (KD value of 49 and 10 pmol/L, respectively) compared with IGF-I (∼10 nmol/L) and blocked binding of IGF-II to IGF-IR, IR-A, a panel of insulin-like growth factor–binding proteins, and the mannose-6-phosphate receptor. A crystal complex of the parental Fab of DX-2647 bound to IGF-II was resolved to 2.2 Å. DX-2647 inhibited IGF-II and, to a lesser extent, IGF-I–induced receptor tyrosine phosphorylation, cellular proliferation, and both anchorage-dependent and anchorage-independent colony formation in various cell lines. In addition, DX-2647 slowed tumor progression in the Hep3B xenograft model, causing decreased tumoral CD31 staining as well as reduced IGF-IIE and IGF-IR phosphorylation levels. Therefore, DX-2647 offers an alternative approach to targeting IGF-IR, blocking IGF-II signaling through both IGF-IR and IR-A. Mol Cancer Ther; 9(6); 1809–19. ©2010 AACR.