bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Inhibition of T-Lymphocyte Activation by Anthrax Toxins In Vivo
Authors: Comer Jason E. , Chopra Ashok K. , Peterson Johnny W. , König Rolf
Published: November 2005

The causative agent of anthrax,Bacillus anthracis, produces two toxins that contribute in part to its virulence. Lethal toxin is a metalloprotease that cleaves upstream mitogen-activated protein kinase kinases. Edema toxin is a calmodulin-dependent adenylate cyclase. Previous studies demonstrated that the anthrax toxins are important immunomodulators that promote immune evasion of the bacterium by suppressing activation of macrophages and dendritic cells. Here we showed that injection of sublethal doses of either lethal or edema toxin into mice directly inhibited the subsequent activation of T lymphocytes by T-cell receptor-mediated stimulation. Lymphocytes were isolated from toxin-injected mice after 1 or 4 days and stimulated with antibodies against CD3 and CD28. Treatment with either toxin inhibited the proliferation of T cells. Injection of lethal toxin also potently inhibited cytokine secretion by stimulated T cells. The effects of edema toxin on cytokine secretion were more complex and were dependent on the length of time between the injection of edema toxin and the isolation of lymphocytes. Treatment with lethal toxin blocked multiple kinase signaling pathways important for T-cell receptor-mediated activation of T cells. Phosphorylation of the extracellular signal-regulated kinase and the stress-activated kinase p38 was significantly decreased. In addition, phosphorylation of the serine/threonine kinase AKT and of glycogen synthase kinase 3 was inhibited in T cells from lethal toxin-injected mice. Thus, anthrax toxins directly act on T lymphocytes in a mouse model. These findings are important for future anthrax vaccine development and treatment.
Pseudomonas aeruginosa
Acquires Biofilm-Like Properties within Airway Epithelial Cells
Authors: Garcia-Medina Raquel , Dunne W. Michael , Singh Pradeep K. , Brody Steven L.
Published: November 2005

Pseudomonas aeruginosa
can notably cause both acute and chronic infection. While several virulence factors are implicated in the acute phase of infection, advances in understanding bacterial pathogenesis suggest that chronic
P. aeruginosa
infection is related to biofilm formation. However, the relationship between these two forms of disease is not well understood. Accumulating evidence indicates that, during acute infection,
P. aeruginosa
enters epithelial cells, a process viewed as either a host-mediated defense response or a pathogenic mechanism to avoid host-mediated killing. We investigated the possibility that epithelial cell entry during early
P. aeruginosa-
epithelial cell contact favors bacterial survival and is linked to chronic infection. Using electron microscopy and confocal microscopy to analyze primary culture airway epithelial cells infected with
P. aeruginosa
, we found that epithelial cells developed pod-like clusters of intracellular bacteria with regional variation in protein expression. Extracellular gentamicin added to the medium after acute infection led to the persistence of intracellular
P. aeruginosa
for at least 3 days. Importantly, compared to bacterial culture under planktonic conditions, the intracellular bacteria were insensitive to growth inhibition or killing by antibiotics that were capable of intraepithelial cell penetration. These findings suggest that
P. aeruginosa
can use airway epithelial cells as a sanctuary for persistence and develop a reversible antibiotic resistance phenotype characteristic of biofilm physiology that can contribute to development of chronic infection.
Whole-Genome Analyses of Speciation Events in Pathogenic Brucellae
Authors: Chain Patrick S. G. , Comerci Diego J. , Tolmasky Marcelo E. , Larimer Frank W. , Malfatti Stephanie A. , Vergez Lisa M. , Aguero Fernan , Land Miriam L. , Ugalde Rodolfo A. , Garcia Emilio
Published: November 2005

Despite their high DNA identity and a proposal to group classical
Brucella
species as biovars of
Brucella melitensis
, the commonly recognized
Brucella
species can be distinguished by distinct biochemical and fatty acid characters, as well as by a marked host range (e.g.,
Brucella suis
for swine,
B. melitensis
for sheep and goats, and
Brucella abortus
for cattle). Here we present the genome of
B. abortus
2308, the virulent prototype biovar 1 strain, and its comparison to the two other human pathogenic
Brucella
species and to
B. abortus
field isolate 9-941. The global distribution of pseudogenes, deletions, and insertions supports previous indications that
B. abortus
and
B. melitensis
share a common ancestor that diverged from
B. suis
. With the exception of a dozen genes, the genetic complements of both
B. abortus
strains are identical, whereas the three species differ in gene content and pseudogenes. The pattern of species-specific gene inactivations affecting transcriptional regulators and outer membrane proteins suggests that these inactivations may play an important role in the establishment of host specificity and may have been a primary driver of speciation in the genus
Brucella
. Despite being nonmotile, the brucellae contain flagellum gene clusters and display species-specific flagellar gene inactivations, which lead to the putative generation of different versions of flagellum-derived structures and may contribute to differences in host specificity and virulence. Metabolic changes such as the lack of complete metabolic pathways for the synthesis of numerous compounds (e.g., glycogen, biotin, NAD, and choline) are consistent with adaptation of brucellae to an intracellular life-style.
Passive Protection against Anthrax by Using a High-Affinity Antitoxin Antibody Fragment Lacking an Fc Region
Authors: Mabry Robert , Rani Mridula , Geiger Robert , Hubbard Gene B. , Carrion Ricardo , Brasky Kathleen , Patterson Jean L. , Georgiou George , Iverson B. L.
Published: November 2005

Passive immunization has been successfully employed for protection against bacterial and viral infections for over 100 years. Immunoglobulin Fc regions play a critical role in the clearance of bacterial pathogens by mediating antibody-dependent and complement-dependent cytotoxicity. Here we show that antibody fragments engineered to recognize the protective antigen component of the
B. anthracis
exotoxin with high affinity and conjugated to polyethylene glycol (PEG) for prolonged circulation half-life confer significant protection against inhalation anthrax despite their lack of Fc regions. The speed and lower manufacturing cost of bacterially expressed PEGylated antibody fragments could provide decisive advantages for anthrax prophylaxis. Importantly, our results suggest that PEGylated antibody fragments may represent a unique approach for mounting a rapid therapeutic response to emerging pathogen infections.
Reduction of Cell Surface Glycosylphosphatidylinositol Conjugates inEntamoeba histolyticaby Antisense Blocking ofE. histolyticaGlcNAc-Phosphatidylinositol Deacetylase Expression: Effect on Cell Proliferation, Endocytosis, and Adhesion to Target Cells
Authors: Vats Divya , Vishwakarma Ram A. , Bhattacharya Sudha , Bhattacharya Alok
Published: November 2005

Glycosylphosphatidylinositol (GPI)-anchored molecules such as cell surface Gal/GalNAc lectin and proteophosphoglycans of the protozoan parasiteEntamoeba histolyticaare thought to be involved in pathogenesis. Here, we report the identification of genes that may be involved in the GPI biosynthetic pathway ofE. histolyticaby use of bioinformatic tools applied to the recently published genome sequence. Of the genes identified, one of the early genes, GlcNAc-phosphatidylinositol deacetylase (PIG-L), was partially characterized. Cell lines deficient inE. histolyticaPIG-L (EhPL-AS) or overproducing it (EhPL-S) were generated by expressing the gene in the antisense or sense orientation, respectively, in a tetracycline-inducible system. The overexpressing cells showed higher EhPIG-L activity and increased production of GlcN-PI. Conversely, cells expressing the antisense RNA displayed reduced GlcN-PI production. The total number of GPI-containing molecules was also reduced in these cells, as demonstrated by Alexa 488 fluorescently labeled proaerolysin labeling. The distribution of GPI-linked PPG and Gal/GalNAc lectin was altered in the tetracycline-induced EhPL-AS cell lines. Further, the antisense-blocked cells showed 36% suppression of cell growth, 50 to 60% inhibition of fluid phase endocytosis, and about 50% inhibition of adhesion to target cells. Therefore, our data suggest the importance of GPI anchors in regulating some of the events in amoebic pathogenesis. They also demonstrated the use of antisense RNA-mediated inhibition of GPI biosynthetic enzymes as an approach to decrease the amount of GPI conjugates inE. histolytica.
Intrapulmonary, Adenovirus-Mediated Overexpression of KARAP/DAP12 Enhances Fungal Clearance during Invasive Aspergillosis
Authors: Carpenter Kristin J. , Buckland Karen F. , Xing Zhou , Hogaboam Cory M.
Published: November 2005

Herein, we report that the intrapulmonary delivery of an adenovirus vector expressing KARAP/DAP12, an adaptor protein expressed in granulocytes and mononuclear cells, enhanced fungal clearance during experimental invasive pulmonary aspergillosis in neutropenic mice.
Clostridium perfringens
Enterotoxin Damages the Human Intestine In Vitro
Authors: Fernández Miyakawa M. E. , Pistone Creydt V. , Uzal F. A. , McClane B. A. , Ibarra C.
Published: November 2005

In vitro,
Clostridium perfringens
enterotoxin (CPE) binds to human ileal epithelium and induces morphological damage concurrently with reduced short-circuit current, transepithelial resistance, and net water absorption. CPE also binds to the human colon in vitro but causes only slight morphological and transport changes that are not statistically significant.
High Susceptibility of Human Dendritic Cells to Invasion by the Intracellular PathogensBrucella suis, B. abortus, andB. melitensis
Authors: Billard Elisabeth , Cazevieille Chantal , Dornand Jacques , Gross Antoine
Published: November 2005

Bacteria from theBrucellagenus are able to survive and proliferate within macrophages. Because they are phylogenetically closely related to macrophages, myeloid dendritic cells (DCs) constitute potential targets forBrucellabacteria. Here we report that DCs display a great susceptibility toBrucellainfection. Therefore, DCs might serve as a reservoir and be important for the development ofBrucellabacteria within their host.
Eosinophils, but Not Eosinophil Peroxidase or Major Basic Protein, Are Important for Host Protection in ExperimentalBrugia pahangiInfection
Authors: Ramalingam Thirumalai , Porte Patricia , Lee James , Rajan T. V.
Published: November 2005

The attenuation of eosinophilia by the administration of monoclonal antibodies to CCR3 consistently correlates with impairment in worm elimination following primary intraperitonealBrugia pahangiinfections in mice. Host protection was unimpaired in mice deficient in eosinophil peroxidase (EPO) or major basic protein 1 (MBP-1), suggesting that eosinophils are essential in host protection but that neither EPO nor MBP-1 alone is.
Azurin of Pathogenic
Neisseria
spp. Is Involved in Defense against Hydrogen Peroxide and Survival within Cervical Epithelial Cells
Authors: Wu Hsing-Ju , Seib Kate L. , Edwards Jennifer L. , Apicella Michael A. , McEwan Alastair G. , Jennings Michael P.
Published: November 2005

Laz, a lipid-modified azurin of the human pathogens
Neisseria gonorrhoeae
and
Neisseria meningitidis
, is involved in defense against oxidative stress and copper toxicity;
laz
mutant strains are hypersensitive to hydrogen peroxide and copper. The
N. gonorrhoeae laz
mutant also has decreased survival in an ex vivo primary human ectocervical epithelial assay.
Different
Helicobacter hepaticus
Strains with Variable Genomic Content Induce Various Degrees of Hepatitis
Authors: Boutin Samuel R. , Shen Zeli , Rogers Arlin B. , Feng Yan , Ge Zhongming , Xu Sandy , Sterzenbach Torsten , Josenhans Christine , Schauer David B. , Suerbaum Sebastian , Fox James G.
Published: November 2005

A 70-kb genomic island (HHGI1) in
Helicobacter hepaticus
strain ATCC 51449 is a putative pathogenicity island (PAI). To determine the in vivo relevance of this PAI, we inoculated A/JCr mice with one of three strains of
H. hepaticus
: type strain Hh3B1, which contains the complete PAI, and strains HhNET and HhG, which lack all or large parts of HHGI1, respectively. Mice infected with HhG and HhNET developed less-severe hepatitis than male A/JCr mice infected with Hh3B1.
Associations between ambient, personal, and indoor exposure to fine particulate matter constituents in Dutch and Finnish panels of cardiovascular patients
Authors: Janssen N A H , Lanki T , Hoek G , Vallius M , de Hartog J J , Van Grieken R , Pekkanen J , Brunekreef B
Published: November 2005

Aims:To assess the relation between ambient, indoor, and personal levels of PM2.5and its elemental composition for elderly subjects with cardiovascular disease.

Methods:In the framework of a European Union funded study, panel studies were conducted in Amsterdam, the Netherlands and Helsinki, Finland. Outdoor PM2.5concentrations were measured at a fixed site. Each subject’s indoor and personal PM2.5exposure was measured biweekly for six months, during the 24 hour period preceding intensive health measurements. The absorbance of PM2.5filters was measured as a marker for diesel exhaust. The elemental content of more than 50% of the personal and indoor samples and all corresponding outdoor samples was measured using energy dispersivexray fluorescence.

Results:For Amsterdam and Helsinki respectively, a total of 225 and 238 personal, and 220 and 233 indoor measurements, were analysed from 36 and 46 subjects. For most elements, personal and indoor concentrations were lower than and highly correlated with outdoor concentrations. The highest correlations (medianr>0.9) were found for sulfur and particle absorbance, which both represent fine mode particles from outdoor origin. Low correlations were observed for elements that represent the coarser part of the PM2.5particles (Ca, Cu, Si, Cl).

Conclusions:The findings of this study provide support for using fixed site measurements as a measure of exposure to particulate matter in time series studies linking the day to day variation in particulate matter to the day to day variation in health endpoints, especially for components of particulate matter that are generally associated with fine particles and have few indoor sources. The high correlation for absorbance of PM2.5documents that this applies to particulate matter from combustion sources, such as diesel vehicles, as well.
An updated study of mortality among North American synthetic rubber industry workers
Authors: Sathiakumar N , Graff J , Macaluso M , Maldonado G , Matthews R , Delzell E
Published: November 2005

Aim:This study evaluated the mortality experience of workers from the styrene-butadiene industry.

Methods:The authors added seven years of follow up to a previous investigation of mortality among 17 924 men employed in the North American synthetic rubber industry. Analyses used the standardised mortality ratios (SMRs) to compare styrene-butadiene rubber workers’ cause specific mortality (1943–98) with those of the United States and the Ontario general populations.

Results:Overall, the observed/expected numbers of deaths were 6237/7242 for all causes (SMR = 86, 95% CI 84 to 88) and 1608/1741 for all cancers combined (SMR = 92, 95% CI 88 to 97), 71/61 for leukaemia, 53/53 for non-Hodgkin’s lymphoma, and 26/27 for multiple myeloma. The 16% leukaemia increase was concentrated in hourly paid subjects with 20–29 years since hire and 10 or more years of employment in the industry (19/7.4, SMR = 258, 95% CI 156 to 403) and in subjects employed in polymerisation (18/8.8, SMR = 204, 95% CI 121 to 322), maintenance labour (15/7.4, SMR = 326, 95% CI 178 to 456), and laboratory operations (14/4.3, SMR = 326, 95% CI 178–546).

Conclusion:The study found that some subgroups of synthetic rubber workers had an excess of mortality from leukaemia that was not limited to a particular form of leukaemia. Uncertainty remains about the specific agent(s) that might be responsible for the observed excesses and about the role of unidentified confounding factors. The study did not find any clear relation between employment in the industry and other forms of lymphohaematopoietic cancer. Some subgroups of subjects had more than expected deaths from colorectal and prostate cancers. These increases did not appear to be related to occupational exposure in the industry.
Incidence by occupation and industry of acute work related respiratory diseases in the UK, 1992–2001
Authors: McDonald J C , Chen Y , Zekveld C , Cherry N M
Published: November 2005

Aims:To summarise incidence rates and epidemiological characteristics of new cases of work related respiratory disease reported by specialist physicians in thoracic and occupational medicine, with particular reference to occupation, industry, and causal agents for asthma, inhalation accidents, and allergic alveolitis.

Methods:Cases reported 1992–2001 to the SWORD and OPRA national surveillance schemes, in which almost all UK chest and occupational physicians participate, were analysed by age, sex, cause, occupation, and industry, with incidence rates calculated against appropriate denominators.

Results:Excluding diseases of long latency, infrequently seen by occupational physicians, the distribution of diagnoses in the two specialties was similar, but with rates generally much higher in occupational than chest physicians. Occupational asthma was responsible for about 25% of cases overall, affecting mainly craft related occupations and machinists, and most often attributed to isocyanates, metals, grains, wood dusts, solders, and welding fume. These same occupations were those at highest risk from inhalation injuries, most frequently caused by irritant gases, vapours, and fume. Among medical technicians and nurses, however, glutaraldehyde and latex were the main causes of occupational asthma. Allergic alveolitis was seldom reported, with almost all cases in agriculture, forestry, and fishing.

Conclusion:During the 10 year period studied, there were few changes in level of reported incidence, apart from some decline in occupational asthma and inhalation injuries. These results and their implications should be distinguished from much higher estimates of asthma made worse by work derived from population surveys, based on prevalence rather than incidence, and self-reported symptoms rather than diagnoses made by specialist physicians. Even so, the reported incidence of new cases of acute respiratory illness caused by work remains substantial.
Prevention of work related eye injuries: long term assessment of the effectiveness of a multicomponent intervention among metal workers
Authors: Mancini G , Baldasseroni A , Laffi G , Curti S , Mattioli S , Violante F S
Published: November 2005

Background:Systematic assessments of the effectiveness of interventions to prevent work related eye injuries are needed.

Aim:To investigate the long term effectiveness of a multicomponent prevention campaign.

Methods:The campaign (conducted in collaboration with the local Employers’ Association and Trade Unions) targeted all 237 metal-ware factories in the district of Imola, Italy. Based on preliminary inspections, the main intervention included distribution to all factories of specific educational brochures and broadcasting/publication of television/radio programmes and local newspaper articles containing expert advice on the subject. This was followed by a four year “post-intervention reinforcement” period of unannounced official inspections. Main outcome measures analysed were eye injury rates (versus non-eye injury rates) among metal workers during “pre-intervention” (1988–90), “peri-intervention” (1991–92), “post-intervention reinforcement” (1993–96), “late post-intervention” (1997–2000), and “very late post-intervention” (2001–03) periods with respect to two comparison sectors (construction and wood/ceramics).

Results:A Poisson regression in which the eye injury rates were modelled for each sector, period, and interaction, adjusting for non-eye injury rates, was chosen. The periods did not by themselves determine an overall reduction in eye injuries. The period/sector interaction terms were related to significant reductions for the metal sector when crossed with the “post-intervention reinforcement” (IRR = 0.77, 95% CI 0.61 to 0.97; % decline = 23.4), the “late post-intervention” (IRR = 0.63, 95% CI 0.50 to 0.79; % decline = 37.4), and the “very late post-intervention” (IRR =  0.58, 95% CI 0.43 to 0.77; % decline = 42.4) periods, suggesting a sustained reduction in eye injury risk following the main intervention.

Conclusion:Results suggest that a carefully coordinated, extensive, multicomponent intervention can lead to lasting reductions in the burden of eye injuries.
Long driving time is associated with haematological markers of increased cardiovascular risk in taxi drivers
Authors: Chen J-C , Chen Y-J , Chang W P , Christiani D C
Published: November 2005

Aims:To examine the association between driving time and changes in haematological markers of increased risks for cardiovascular diseases (CVD).

Methods:The authors conducted a cross sectional analysis of baseline data from the Taxi Drivers’ Health Study cohort in Taipei, Taiwan. They retrieved information on comorbidity, laboratory tests, age, and anthropometric measures from medical records of 1157 subjects (mean age 44.6 (SD 8.6) years). Whole blood cell (WBC) count was used as the primary haematological marker for increased CVD risk, and platelet count and haematocrit as the secondary markers. Standardised questionnaires were implemented to collect information on demographics, lifestyle, work related physical and psychosocial factors, and driving time profiles. Multiple regression was used to estimate the adjusted effects of driving time on three haematological markers.

Results:The mean measured hematological marker was 6656 (SD 1656) cells ×106/l for WBC, 47.2 (SD 3.5) % for hematocrit, and 243 (SD 52) cells ×109/l for platelets. The driving time was 264 (SD 76) hours/month. Compared with drivers who drove ⩽208 hours/month (1st quartile cut off), drivers who drove >208 hours/month had a higher WBC count (by 317 ×106/l; 95% CI 99 to 535), haematocrit (by 0.8%; 95% CI 0.3 to 1.2), and platelets (7.9 ×109/l; 95% CI 1.0 to 14.8). After adjusting for conventional CVD risk factors (age, sex, smoking, hypertension, diabetes, and hypercholesterolaemia), obesity, alcohol drinking, regular exercise, and sociodemographics (education, marital status, income, and so on), long driving time was still associated with significant increases in WBC and platelets, whereas the effect on haematocrit was diminished and became statistically non-significant. Additional controls for physical workload, self-perceived job stress, and job dissatisfaction did not alter the associations with increased WBC and platelets.

Conclusions:Longitudinal studies are needed to confirm the observed cross sectional association and to further examine the specific occupational exposures accountable for the association between driving time and haematological markers of systemic inflammation and haemostatic alteration.
PLASMON EXCITATIONS IN METAL CLUSTERS AND FULLERENES
Authors: SOLOV'YOV ANDREY V.
Published: November 2005

This paper gives a survey of physical phenomena manifesting themselves in electron and photon collisions with atomic clusters. The emphasis is made on electron scattering, photoabsorption and photoionization of fullerenes and metal clusters, however some results are applicable to other types of clusters as well. It is demonstrated that the diffraction and interference phenomena play an important role in the processes of clusters interaction with photons and electrons. The essential role of the multipole surface and volume plasmon excitations is elucidated in the formation of electron energy loss spectra on clusters as well as in the total inelastic scattering cross sections and in multiphoton absorption regime. Attention is paid to the elucidation of the role of the polarization interaction in low energy electron-cluster collisions. This problem is considered for the electron attachment to metallic clusters and the plasmon enhanced photon emission. The mechanisms of electron excitation widths formation and the relaxation of electron excitations in metal clusters and fullerenes are discussed.
URBAN TRAFFIC CONGESTION SPREADING IN SMALL WORLD NETWORKS
Authors: SUN HUIJUN , WU JIANJUN
Published: November 2005

In this paper, two definitions about traffic congestion are proposed. We describe the traffic congestion spreading with the SEIR model of a complex small-world network. In addition, the relationships among the congestion factor, the number of average infection, the average recover rate and the infection rate are given by simulations in general traffic congestion conditions.
APPLICATION OF THE GENETIC ALGORITHM TO BLUME–EMERY–GRIFFITHS MODEL: TEST CASES
Authors: CANKO OSMAN , ŞAHİN MEHMET , ERDİNÇ AHMET
Published: November 2005

The equilibrium properties of the Blume–Emery–Griffiths (BEG) model Hamiltonian with the arbitrary bilinear (J), biquadratic (K) and crystal field interaction (D) are studied using the genetic algorithm technique. Results are compared with lowest approximation of the cluster variation method (CVM), which is identical to the mean field approximation. We found the genetic algorithm to be very efficient for fast search at the average fraction of the spins, especially in the early stages as the system is far from the equilibrium state. A combination of the genetic algorithm followed by one of the well-tested simulation techniques seems to be an optimal approach. The curvature of the inverse magnetic susceptibility is also presented for the stable state of the BEG model.
STOCHASTIC AND DISCRETE TIME MODELS OF LONG-RANGE TURBULENT TRANSPORT IN THE SCRAPE-OFF LAYER
Authors: VOLCHENKOV D. , LIMA R.
Published: November 2005

The two dimensional stochastic time model of scrape-off layer (SOL) turbulent transport is studied. The instability arisen in the system with respect to the stochastic perturbations of both either density or vorticity reveals itself in the strong outward bursts of particle density propagating ballistically across the SOL. The stability and possible stabilization of the cross-field turbulent system depend very much upon the reciprocal correlation time between density and vorticity fluctuations. The probability distribution function (pdf) of the particle flux for the large magnitudes of flux events can be modeled with a simple discrete time toy model of random walks concluding at a boundary. The spectra of wandering times feature the pdf of particle flux in the model and qualitatively reproduce the experimental statistics of transport events.
FCILINK: Mining Frequent Closed Itemsets Based on a Link Structure between Transactions
Authors: Han Kyong Rok , Kim Jae Yearn
Published: November 2005

The problem of discovering association rules between items in a database is an emerging area of research. Its goal is to extract significant patterns or interesting rules from large databases. Recent studies of mining association rules have proposed a closure mechanism. It is no longer necessary to mine the set of all of the frequent itemsets and their association rules. Rather, it is sufficient to mine the frequent closed itemsets and their corresponding rules. In the past, a number of algorithms for mining frequent closed itemsets have been based on items. In this paper, we use the transaction itself for mining frequent closed itemsets. An efficient algorithm called FCILINK is proposed that is based on a link structure between transactions. A given database is scanned once and then a much smaller sub-database is scanned twice. Our experimental results show that our algorithm is faster than previously proposed methods. Furthermore, our approach is significantly more efficient for dense databases.
An Efficient Approach for Candidate Set Generation
Authors: Malhis Nawar , Ruttan Arden , Refai Hazem H.
Published: November 2005

When Apriori was first introduced as an algorithm for discovering association rules in a database of market basket data, the problem of generating the candidate set of the large set was a bottleneck in Apriori's performance, both in space and computational requirements. At first, many unsuccessful attempts were made to improve the generation of a candidate set. Later, other algorithms that out performed Apriori were developed that generate association rules without using a candidate set. They used the counting property of association rules instead of generating the candidate set as Apriori does. However, the Apriori concept has been used in many different areas other than counting market basket items, and the candidate generation problem remains a bottleneck issue. The approach described here improves the overall time and space requirements by eliminating the need for a hash table/tree of formation for the candidate set.
Problem-based learning and the medical school: another case of the emperor’s new clothes?
Authors: Butler Richard , Inman David , Lobb Derek
Published: November 2005

For almost four decades, problem-based learning (PBL) has been the stated cornerstone of learning in many medical schools. Proponents of PBL cite the open nature of the learning experience where students are free to study in depth, unencumbered by the burdens of broad courses based on the memorization of facts; detractors, on the other hand, cite the lack of breadth and factual knowledge required for professional qualification. Both points of view have merit. Professional schools have a different set of needs and requirements, and it is these that drive the curriculum and learning philosophies. The constraints of the professional school are so different from those of the purely academic environment that PBL, while admirably suited to the latter, is just problem solving in the former.
International Union of Physiological Sciences Teaching Workshop, April 7–10, 2005, Pali Mountain, California
Authors: Hansen Penelope A. , Sefton Ann Jervie
Published: November 2005

Hansen, Penelope A., and Ann Jervie Sefton. International Union of Physiological Sciences Teaching Workshop, April 7–10, 2005, Pali Mountain, California. Adv Physiol Educ289: 216–226, 2005; doi:10.1152/advan.00053.2005.—Fifty-six physiologists from fourteen countries participated in the sixth International Union of Physiological Sciences Teaching Workshop. The four-day program included a poster session, a debate on integrative versus disciplinary curricula, and interactive lectures on evidence-based education, inquiry laboratories, and student preparation for physiology courses. Participants worked in small groups on one of four topics: developing free web-based laboratory resources, information technology, curriculum planning and design, and other issues in classroom teaching.
Spontaneous electrical rhythmicity and the role of the sarcoplasmic reticulum in the excitability of guinea pig gallbladder smooth muscle cells
Authors: Balemba Onesmo B. , Salter Matthew J. , Heppner Thomas J. , Bonev Adrian D. , Nelson Mark T. , Mawe Gary M.
Published: November 2005

Spontaneous action potentials and Ca2+transients were investigated in intact gallbladder preparations to determine how electrical events propagate and the cellular mechanisms that modulate these events. Rhythmic phasic contractions were preceded by Ca2+flashes that were either focal (limited to one or a few bundles), multifocal (occurring asynchronously in several bundles), or global (simultaneous flashes throughout the field). Ca2+flashes and action potentials were abolished by inhibiting sarcoplasmic reticulum (SR) Ca2+release via inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] channels with 2-aminoethoxydiphenyl borate and xestospongin C or by inhibiting voltage-dependent Ca2+channels (VDCCs) with nifedipine or diltiazem or nisoldipine. Inhibiting ryanodine channels with ryanodine caused multiple spikes superimposed upon plateaus of action potentials and extended quiescent periods. Depletion of SR Ca2+stores with thapsigargin or cyclopiazonic acid increased the frequency and duration of Ca2+flashes and action potentials. Acetylcholine, carbachol, or cholecystokinin increased synchronized and increased the frequency of Ca2+flashes and action potentials. The phospholipase C (PLC) inhibitor U-73122 did not affect Ca2+flash or action potential activity but inhibited the excitatory effects of acetylcholine on these events. These results indicate that Ca2+flashes correspond to action potentials and that rhythmic excitation in the gallbladder is multifocal among gallbladder smooth muscle bundles and can be synchronized by excitatory agonists. These events do not depend on PLC activation, but agonist stimulation involves activation of PLC. Generation of these events depends on Ca2+entry via VDCCs and on Ca2+mobilization from the SR via Ins(1,4,5)P3channels.
Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity
Authors: Pimentel Mark , Lin Henry C. , Enayati Pedram , van den Burg Brian , Lee Hyo-Rang , Chen Jin H. , Park Sandy , Kong Yuthana , Conklin Jeffrey
Published: November 2005

The presence of methane on lactulose breath test among irritable bowel syndrome (IBS) subjects is highly associated with the constipation-predominant form. Therefore, we set out to determine whether methane gas can alter small intestinal motor function. In dogs, small intestinal fistulae were created to permit measurement of intestinal transit. Using a radiolabel, we evaluated transit during infusion of room air and subsequently methane. In this model, small intestinal infusion of methane produced a slowing of transit in all dogs by an average of 59%. In a second experiment, guinea pig ileum was pinned into an organ bath for the study of contractile activity in response to brush strokes applied to the mucosa. The force of contraction was measured both orad and aborad to the stimulus. The experiment was repeated while the bath was gassed with methane. Contractile activities orad and aborad to the stimulus were significantly augmented by methane compared with room air ( P < 0.05). In a third experiment, humans with IBS who had undergone a small bowel motility study were compared such that subjects who produced methane on lactulose breath test were compared with those producing hydrogen. The motility index was significantly higher in methane-producing IBS patients (1,851 ± 861) compared with hydrogen producers (1,199 ± 301) ( P < 0.05). Therefore, methane, a gaseous by-product of intestinal bacteria, slows small intestinal transit and appears to do so by augmenting small bowel contractile activity.
Inhaled nitric oxide does not reduce systemic vascular resistance in mice
Authors: Hataishi Ryuji , Zapol Warren M. , Bloch Kenneth D. , Ichinose Fumito
Published: November 2005

Inhaled nitric oxide (NO) is a highly selective pulmonary vasodilator. It was recently reported that inhaled NO causes peripheral vasodilatation after treatment with a NO synthase (NOS) inhibitor. These findings suggested the possibility that inhibition of endogenous NOS uncovered the systemic vasodilating effect of NO or NO adducts absorbed via the lungs during NO inhalation. To learn whether inhaled NO reduces systemic vascular resistance in the absence of endothelial NOS, we studied the systemic vascular effects of NO breathing in wild-type mice treated without and with the NOS inhibitor Nω-nitro-l-arginine methyl ester and in NOS3-deficient (NOS3−/−) mice. During general anesthesia, the cardiac output, left ventricular function, and systemic vascular resistance were not altered by NO breathing at 80 parts/million in both genotypes. Breathing NO in air did not alter blood pressure and heart rate, as measured by tail-cuff and telemetric methods, in either awake wild-type mice (whether or not they were treated with Nω-nitro-l-arginine methyl ester), or in awake NOS3−/− mice. Our findings suggest that absorption of NO or adducts during NO breathing is insufficient to cause systemic vasodilation in mice, even when endogenous endothelial NO production is congenitally absent.
A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia
Authors: Kaneko Kazuhiro , Yonemitsu Yoshikazu , Fujii Takaaki , Onimaru Mitsuho , Jin Chen-Hao , Inoue Makoto , Hasegawa Mamoru , Onohara Toshihiro , Maehara Yoshihiko , Sueishi Katsuo
Published: November 2005

The therapeutic use of angiogenic factors shows promise in the treatment of critical limb ischemia; however, its potential for myonephropathic metabolic syndrome (MNMS), a fatal complication caused by arterial reconstruction, has not been elucidated. The objective of this study was to evaluate the effectiveness of recombinant Sendai virus-mediated gene transfer of fibroblast growth factor-2 (FGF-2) directly compared with that of a radical scavenger, MCI-186, in a rat model of MNMS. MNMS was surgically induced by aortic occlusion below renal arteries for 4 h, followed by 6 h of reperfusion. Administration of MCI-186 (twice; iv 5 min before induced ischemia and ip 5 min before reperfusion; 10 mg/kg, respectively), but not FGF-2 gene transfer (once, 48 h before induced ischemia), dramatically prevented the increase of serum biochemical markers as well as the edema of the gastrocnemius muscle. The effect of MCI-186 was accompanied by the marked suppression of the neutrophilic infiltration into the local (muscle) and remote (lung) organs. Although serum and muscular levels of a neutrophil-chemoattractant (growth-related oncogene/cytokine-induced neutrophil chemoattractant-1) were not affected by any treatment, the serum level of soluble intercellular adhesion molecule-1 was decreased by treatment with MCI-186 but not by treatment with FGF-2. These results suggest the distinct mechanism of MNMS from critical limb ischemia without reperfusion. Therefore, radical scavenging should be paid more attention than therapeutic angiogenesis when arterial circulation is reconstructed.
Cortical spreading depression confounds concentration-dependent pial arteriolar dilation during N-methyl-d-aspartate superfusion
Authors: Ayata Cenk , Moskowitz Michael A.
Published: November 2005

Pial arterioles do not express N-methyl-d-aspartate (NMDA) receptors but dilate in response to topical NMDA application. We explored the mechanism underlying NMDA-mediated responses in murine pial arterioles (11–31 μm), using a closed cranial window preparation, and found that arteriolar dilation was not concentration dependent. Pial arteriolar diameter abruptly increased within 3 min of superfusing 50 or 100 μM NMDA. Dilation reached a peak within 1 min (46 ± 14%) and then declined to a plateau (28 ± 13%) for the duration of superfusion. Whereas a higher concentration (200 μM) did not produce further dilation, lower concentrations (1–10 μM) did not dilate the arterioles at all. MK-801 (10 μM) abrogated the dilation response, whereas Nω-nitro-l-arginine (1 mM) attenuated the peak and abolished the sustained dilation during NMDA superfusion. We determined that NMDA-induced pial arteriolar responses were evoked by cortical spreading depression, because abrupt vasodilation during 50 or 100 μM NMDA superfusion was associated with a large negative slow potential shift and electrocorticogram suppression that spread from the superfusion window to distant cortical areas. Our data suggest that the responses of pial arterioles to NMDA are caused in part by neurovascular coupling due to cortical spreading depression.
Contribution of proliferation and DNA damage repair to alveolar epithelial type 2 cell recovery from hyperoxia
Authors: Lee Jooeun , Reddy Raghava , Barsky Lora , Weinberg Kenneth , Driscoll Barbara
Published: November 2005

In this study, C57BL/6J mice were exposed to hyperoxia and allowed to recover in room air. The sublethal dose of hyperoxia for C57BL/6J was 48 h. Distal lung cellular isolates from treated animals were characterized as 98% epithelial, with minor fibroblast and endothelial cell contaminants. Cells were then verified as 95% pure alveolar epithelial type II cells (AEC2) by surfactant protein C (SP-C) expression. After hyperoxia exposure in vivo, fresh, uncultured AEC2 were analyzed for proliferation by cell yield, cell cycle, PCNA expression, and telomerase activity. DNA damage was assessed by TdT-dUTP nick-end labeling, whereas induction of DNA repair was evaluated by GADD-153 expression. A baseline level for proliferation and damage was observed in cells from control animals that did not alter significantly during acute hyperoxia exposure. However, a rise in these markers was observed 24 h into recovery. Over 72 h of recovery, markers for proliferation remained elevated, whereas those for DNA damage and repair peaked at 48 h and then returned back to baseline. The expression of GADD-153 followed a distinct course, rising significantly during acute exposure and peaking at 48 h recovery. These data demonstrate that in healthy, adult male C57BL/6J mice, AEC2 proliferation, damage, and repair follow separate courses during hyperoxia recovery and that both proliferation and efficient repair may be required to ensure AEC2 survival.
Induction of secondary apoptosis, inflammation, and lung fibrosis after intratracheal instillation of apoptotic cells in rats
Authors: Wang Liying , Scabilloni James F. , Antonini James M. , Rojanasakul Yon , Castranova Vincent , Mercer Robert R.
Published: November 2005

Uncontrolled apoptosis has been associated with several pulmonary disorders; however, the molecular mechanism underlying this process and the fate of apoptotic cells in vivo are unclear. Here we show that direct administration of apoptotic cells to the lungs of rats caused pulmonary inflammation and fibrosis, as indicated by emigration of inflammatory cells to the air spaces, TNF-α immunoreactivity, and connective tissue accumulation, indicating a direct relationship between apoptotic cells and the observed lung pathologies. To determine how the lungs process the accumulated apoptotic cells, normal or apoptotic cells from autologous donor rats were labeled with fluorescent nanobeads and intratracheally instilled into the lungs of rats. Probe distribution and lung cell apoptosis were determined at various times over a 28-day period by confocal fluorescence microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, respectively. Labeled apoptotic cells were cleared by lung macrophages within 1 wk after the treatment. However, the total number of apoptotic cells in the lung remained high at 28 days posttreatment. The results indicate a continuous induction of secondary apoptosis by apoptotic cell instillation, which may contribute to the observed lung pathology. Analysis of lung cell apoptosis by caspase assays showed an elevation of caspase-8 but not caspase-9 in the treatment group at 28 days posttreatment, indicating involvement of the death receptor-mediated pathway in the apoptotic process. Together, our results demonstrate a direct effect of apoptotic cell accumulation on inflammatory and fibrotic pulmonary responses and the continuous induction of lung cell apoptosis by apoptotic cell instillation.
Pneumococci induced TLR- and Rac1-dependent NF-κB-recruitment to the IL-8 promoter in lung epithelial cells
Authors: Schmeck Bernd , Huber Sylvia , Moog Kerstin , Zahlten Janine , Hocke Andreas C. , Opitz Bastian , Hammerschmidt Sven , Mitchell Tim J. , Kracht Michael , Rosseau Simone , Suttorp Norbert , Hippenstiel Stefan
Published: November 2005

Streptococcus pneumoniae is the major pathogen of community-acquired pneumonia. The respiratory epithelium constitutes the first line of defense against invading lung pathogens, including pneumococci. We analyzed the involvement of Toll-like receptors (TLR) and Rho-GTPase signaling in the activation of human lung epithelial cells by pneumococci. S. pneumoniae induced release of interleukin-8 (IL-8) by human bronchial epithelial cell line BEAS-2B. Specific inhibition of Rac1 by Nsc23766 or a dominant-negative mutant of Rac1 strongly reduced cytokine release. In addition, pneumococci-related cell activation (IL-8 release, NF-κB-activation) depended on MyD88, phosphatidylinositol 3-kinase, and Cdc42 but not on RhoA. Pneumococci enhanced TLR1 and TLR2 mRNA expression in BEAS-2B cells, whereas TLR4 and TLR6 expression was constitutively high. TLR1 and 2 synergistically recognized pneumococci in cotransfection experiments. TLR4, TLR6, LPS-binding protein, and CD14 seem not to be involved in pneumococci-dependent cell activation. At the IL-8 gene promoter, recruitment of phosphorylated NF-κB subunit p65 was blocked by inhibition of Rac1, whereas binding of the phosphorylated activator protein-1 subunit c-Jun to the promoter was not diminished. In summary, these results suggest that S. pneumoniae activate human epithelial cells by TLR1/2 and a phosphatidylinositol 3-kinase- and Rac1-dependent NF-κB-recruitment to the IL-8 promoter.
Regulatory features of interleukin-1β-mediated prostaglandin E2 synthesis in airway smooth muscle
Authors: Pascual Rodolfo M. , Carr Elizabeth M. , Seeds Michael C. , Guo Manhong , Panettieri Reynold A. , Peters Stephen P. , Penn Raymond B.
Published: November 2005

Exposure of airway smooth muscle (ASM) cells to the cytokine IL-1β results in an induction of PGE2 synthesis that affects numerous cell functions. Current dogma posits induction of COX-2 protein as the critical, obligatory event in cytokine-induced PGE2 production, although PGE2 induction can be inhibited without a concomitant inhibition of COX-2. To explore other putative regulatory features we examined the role of phospholipase A2 (PLA2) and PGE synthase (PGES) enzymes in IL-1β-induced PGE2 production. Treatment of human ASM cultures with IL-1β caused a time-dependent induction of both cytosolic PLA2 (cPLA2) and microsomal PGES (mPGES) similar to that observed for COX-2. Regulation of COX-2 and mPGES induction was similar, being significantly reduced by inhibition of p42/p44 or p38, whereas cPLA2 induction was only minimally reduced by inhibition of p38 or PKC. COX-2 and mPGES induction was subject to feed-forward regulation by PKA, whereas cPLA2 induction was not. SB-202474, an SB-203580 analog lacking the ability to inhibit p38 but capable of inhibiting IL-1β-induced PGE2 production, was effective in inhibiting mPGES but not COX-2 or cPLA2 induction. These data suggest that although COX-2, cPLA2, and mPGES are all induced by IL-β in human ASM cells, regulatory features of cPLA2 are dissociated, whereas those of COX-2 and mPGES are primarily associated, with regulation of PGE2 production. mPGES induction and, possibly, cPLA2 induction appear to cooperate with COX-2 to determine IL-1β-mediated PGE2 production in human ASM cells.