bluuebunny/crossref_metadata_2025 huggingface dataset:
First Molecular Detection of R. conorii, R. aeschlimannii, and R. massiliae in Ticks from Algeria
Authors: BITAM I. , PAROLA P. , MATSUMOTO K. , ROLAIN J. M. , BAZIZ B. , BOUBIDI S. C. , HARRAT Z. , BELKAID M. , RAOULT DIDIER
Published: November 2006

Abstract:  Ticks collected in Northern Algeria between May 2001 and November 2003 were tested by PCR for the presence of Rickettsia spp. DNA using primer amplifying gltA and OmpA genes. Three different spotted fever group rickettsias were amplified from these ticks: R. Conorii subsp. P. conorii strain Malish in Rhipicephalus sanguineus, R. aeschlimannii in Hyalomma marginatum, and R. massiliae in Rhipicephalus turanicus. Our results confirm the presence of R. conorii in ticks in Algeria and provide the first detection of R. aeschlimannii and R. massiliae in Algeria.
Characterization of Dermacentor variabilis Molecules Associated with Rickettsial Infection
Authors: MACALUSO KEVIN R. , MULENGA ALBERT , SIMSER JASON A. , AZAD ABDU F.
Published: November 2006

Abstract:  To ultimately define the virulence factors of rickettsiae, an understanding of the biology of the organism is essential. Comprehension of the pathogen–human interaction is critical to the development of control measures; and, in the case of vector‐borne diseases, the role of the vector in maintaining and transmitting pathogens to vertebrate hosts is crucial to ultimate control. Recent studies have identified tick molecules that are likely involved in the tick–rickettsiae interchange, including tick response to infection and possible molecules exploited by rickettsiae during transmission events. We have further characterized several tick‐derived molecules, including a histamine release factor, serine proteases, and lysozymes.
Molecular Characterization of Rickettsia rickettsii Infecting Dogs and People in North Carolina
Authors: KIDD LINDA , HEGARTY BARBARA , SEXTON DANIEL , BREITSCHWERDT EDWARD
Published: November 2006

Abstract:  Rocky Mountain spotted fever (RMST) is an important cause of morbidity and mortality in people and dogs in the United States. Disease manifestations are strikingly similar in both species, and illness in dogs can precede illness in people. R. rickettsii has been identified as a Select Agent by the CDC as a Category C priority pathogen by the National Institute of Allergic and Infectious Diseases because it is amenable to use as a bioterror agent. The clinical and temporal relationship of naturally occurring diseases in dogs and people suggests that dogs could serve as sentinels for natural infection and bioterrorist attacks using this organism. Recognizing genetic modifications in naturally occurring disease agents in order to distinguish them from intentionally released agents are priorities put forth by the NIAID. To determine whether the rickettsiae naturally infecting dogs is the same as those that infect persons in a given geographical region, we characterized rickettsial isolates obtained from three dogs and two persons diagnosed with RMSF in North Carolina. Portions of three genes (ompA,rrs, and gltA) amplified by PCR were cloned and sequenced or directly sequenced. Reactions were run in duplicate in forward and reverse directions. Gene sequences were aligned with known sequences deposited in GenBank and with each other. Sequences of the 5′ region of the ompA gene were 100% homologous with a tick strain (Bitterroot) of R. rickettsii for all five isolates. Sequences of the rrs gene were 99.8 99.9% homologous with a tick strain (Sawtooth) of R. rickettsii. rrs gene sequences from one dog and the two persons was identical. Sequences of one dog isolate differed from these by one base pair. Sequences from another dog isolate differed by two base pairs. Sequences of the gltA gene are pending. This confirms on a molecular level that R. rickettsii causing naturally occurring RMSF in dogs in North Carolina is highly homologous to R. rickettsii that causes the disease in people in the same region. Sequence data will be deposited in GenBank, thereby providing genetic information regarding naturally occurring R. rickettsii.
Focusing on Host–Vector–Pathogen Interactions for Vaccine Development
Authors: FUENTE JOSÉde la , AYOUBI PATRICIA , BLOUIN EDMOUR F. , ALMAZÁN CONSUELO , NARANJO VICTORIA , KOCAN KATHERINE M.
Published: November 2006

Abstract: 
Anaplasma marginale and A. phagocytophylum are intracellular rickettsiae that cause bovine anaplasmosis and human granulocytic anaplasmosis, respectively. The ultimate vaccine for the control of anaplasmosis would be one that reduces infection and transmission of the pathogen by ticks. Effective vaccines for control of anaplasmosis are not available despite attempts using different approaches, such as attenuated strains, infected erythrocyte and tick cell‐derived purified antigens, and recombinant pathogen and tick‐derived proteins. Three lines of functional analyses were conducted by our laboratory to characterize host–tick–Anaplasma interactions to discover potential vaccine candidate antigens to control tick infestations and the infection and transmission of Anaplasma spp.: (1) characterization of A. marginale adhesins involved in infection and transmission of the pathogen, (2) global expression analysis of genes differentially expressed in HL‐60 human promyelocytic cells in response to infection with A. phagocytophilum, and (3) identification and characterization of tick‐protective antigens by expression library immunization (ELI) and analysis of expressed sequence tags (EST) in a mouse model of tick infestations and by RNA interference in ticks. These experiments have resulted in the characterization of the A. marginale MSP1a as an adhesin for bovine erythrocytes and tick cells, providing support for its use as candidate vaccine antigen for the control of bovine . Microarray analysis of genes differentially expressed in human cells infected with A. phagocytophilum identified key molecules involved in pathogen infection and multiplication. The screening for tick‐protective antigens resulted in vaccine candidates reducing tick infestation, molting, and oviposition and affecting Anaplasma infection levels in ticks.
New Findings on Members of the Family Anaplasmataceae of Veterinary Importance
Authors: RIKIHISA YASUKO
Published: November 2006

Abstract:  Members of the family Anaplasmataceae are obligate intracellular Gram‐negative bacteria that naturally infect a variety of wild and domestic animal species, the spillover of which may lead to zoonosis. I discuss new findings on members of the family Anaplasmataceae of veterinary importance and therefore, I will describe the recent findings on Neorickettsia risticii in the trematode and related Neorickettsia species. I also will review the recent progress on Aegyptianella pullorum and other Aegyptianella sp., “Candidatus Neoehrlichia mikurensis” and Anaplasma phagocytophilum strains in various hosts. The whole genome sequences of two important veterinary pathogens—Anaplasma marginale, the bovine anaplasmosis agent, and Ehrlichia (formerly Cowdria) ruminantium, the agent of heartwater of ruminants—have been published. Taken together, these advances in research of the family Anaplasmataceae in the veterinary field provide us with insights into the evolution, reservoir, and transmission of these organisms in nature and their pathogenesis in natural and accidental hosts. It is through this work that surveillance, diagnosis, preventive measures, and treatment of ehrlichioses of both animals and humans can be improved.
Cytokine Gene Expression by Peripheral Blood Leukocytes in Dogs Experimentally Infected with a New Virulent Strain of Ehrlichia canis
Authors: UNVER AHMET , HUANG HAIBIN , RIKIHISA YASUKO
Published: November 2006

Abstract: 
Ehrlichia canis (E. canis) is a lipopolysaccharide (LPS)‐deficient obligatory intracellular bacterium that causes canine monocytic ehrlichiosis, a chronic febrile disease accompanied with hematological abnormality. This study analyzed temporal expression levels of IL‐1β, IL‐2, IL‐6, IL‐8, IFN‐γ, and TNF‐α mRNA by peripheral blood leukocytes from dogs experimentally infected with a new virulent strain of E. canis by using real‐time RT‐PCR. Relative levels of IL‐1β and IL‐8 transcripts normalized by the β‐actin transcript levels, were significantly upregulated, whereas those of TNF‐α and IFN‐γ transcripts were only weakly upregulated in all three infected dogs, starting from 2 days up to 52 days post inoculation. The expressions of IL‐2 and IL‐6 genes were extremely low compared with the positive control (ConA‐stimulated canine peripheral blood leukocytes). This study showed that E. canis can induce chronic expression of a subset of proinflammatory cytokine genes: balance, timing, and duration of these cytokine generations may contribute to the progression of canine ehrlichiosis.
Understanding the Mechanisms of Transmission of Ehrlichia ruminantium and Its Influence on the Structure of Pathogen Populations in the Field
Authors: VACHIÉRY NATHALIE , RALINIAINA MODESTINE , STACHURSKI FRÉDÉRIC , ADAKAL HASSANE , MOLIA SOPHIE , LEFRANÇOIS THIERRY , MARTINEZ DOMINIQUE
Published: November 2006

Abstract:  The understanding of the structure of Ehrlichia ruminantium stock population in the field was highlighted by experiments done in controlled conditions on the goat model. The mixture of strains observed in ticks seemed to be due to simultaneous infections rather than successive infections of the carrier. During a dual infection, the timing of Ehrlichia ruminantium circulation of the two stocks in hosts influenced their selection by ticks.
Incidence of Ovine Abortion by Coxiella burnetii in Northern Spain
Authors: OPORTO B. , BARANDIKA J.F. , HURTADO A. , ADURIZ G. , MORENO B. , GARCIA‐PEREZ A.L.
Published: November 2006

Abstract:  The infectious causes of ovine abortion occurring in 148 farms in northern Spain between 1999 and 2003 were investigated. Laboratory analysis included microbiological, serological, pathological and molecular techniques. Border disease was diagnosed in 16% of the flocks, toxoplasmosis in 15%, chlamydiosis in 12%, salmonellosis in 10%, Q fever in 3%, miscellaneous infections in 7% (Yersinia spp., Listeria spp., Brucella spp.), and inflammatory lesions compatible with an infectious cause were seen in 7% of the flock. In an additional 1% of the flocks non‐infectious causes were identified, and a diagnosis was not reached in 38% of the flocks. When a PCR retrospective study was carried out to investigate the possible implication of Coxiella burnetii in the cases without diagnosis, including those with inflammatory lesions, the prevalence of this pathogen increased from 3% up to 9% of the flocks, revealing the importance of this zoonotic pathogen as a small‐ruminant abortifacient agent. Placenta was the most commonly positive sample, but other fetal tissues were also of value for C. burnetii DNA detection. The present results update information about the situation of abortion in sheep farms in northern Spain, and highlight the relevance of molecular diagnostic tools in routine laboratory analysis of abortions by C. burnetii.
Molecular Survey of Ehrlichia canis and Anaplasma phagocytophilum from Blood of Dogs in Italy
Authors: SOLANO‐GALLEGO L. , TROTTA M. , RAZIA L. , FURLANELLO T. , CALDIN M.
Published: November 2006

Abstract:  We investigated the prevalence of Ehrlichia canis (E. canis) (n= 601) and Anaplasma phagocytophilum (A. phagocytophilum) (n= 460) infection by means of real‐time PCR from blood of Italian dogs. The prevalence of E. canis in northern, central, and southern Italy was 2.9%, 8%, and 9.7%, respectively. The prevalence of A. phagocytophilum was 0%.
Comparison of Four Commercially Available Assays for the Detection of IgM Phase II Antibodies to Coxiella burnetii in the Diagnosis of Acute Q Fever
Authors: FRANGOULIDIS DIMITRIOS , SCHRÖPFER ELMAR , DAHOUK SASCHA AL , TOMASO HERBERT , MEYER HERMANN
Published: November 2006

Abstract:  Four commercially available serological assays for the detection of IgM phase II antibodies in patients with acute Q fever infection were compared using a panel of 23 serum samples from patients with acute Q fever and 88 control sera from blood donors.
Evaluation of IgG Antibody Response against Rickettsia conorii and Rickettsia slovaca in Patients with DEBONEL/TIBOLA
Authors: SANTIBÁÑEZ S. , IBARRA V. , PORTILLO A. , BLANCO J.R. , De ARTOLA V. MARTÍNEZ , GUERRERO A. , OTEO J.A.
Published: November 2006

Abstract:  The aim of the study was to determine the IgG antibody response to spotted fever group Rickettsia (SFGR) R. conorii and R. slovaca, and its specificity and sensitivity in patients with DEBONEL/TIBOLA. A prospective study of 31 patients with DEBONEL was carried out from January 2001 to May 2004. The SFGR serology testing (IgG IFA) for the diagnosis of DEBONEL/TIBOLA showed 61% sensitivity and 100% specificity. The R. slovaca antigen allowed the diagnoses in 18 of the 31 patients (58%), and 17 patients (55%) were diagnosed with this disease using R. conorii antigen. Therefore, using R. slovaca as antigen did not improve the sensitivity of the assay.
Molecular Typing of Novel Rickettsia rickettsii Isolates from Arizona
Authors: EREMEEVA MARINA E. , BOSSERMAN ELIZABETH , ZAMBRANO MARIA , DEMMA LINDA , DASCH GREGORY A.
Published: November 2006

Abstract:  Seven isolates of Rickettsia rickettsii were obtained from a skin biopsy, two whole‐blood specimens, and from Rhipicephalus sanguineus ticks from eastern Arizona. Molecular typing of seven isolates of R. rickettsii and DNA samples from two other Rh. sanguineus ticks infected with R. rickettsii was conducted by PCR and DNA sequencing of rompA and 12 variable‐number tandem repeat regions (VNTRs). All DNA specimens from Arizona were identical to each other and to reference human and Dermacentor andersoni isolates of R. rickettsii from Montana in their rOmpA gene sequences and 10 VNTRs. Two of the twelve VNTRs had differences in the number of repeat sequences in isolates from Arizona compared to those from Montana, thus conferring the novelty of the Rh. sanguineus‐associated R. rickettsii
Monitoring of Humans and Animals for the Presence of Various Rickettsiae and Coxiella burnetii by Serological Methods
Authors: KOVÁČOVÁ E. , SEKEYOVÁ Z. , TRÁVNIČEK M. , BHIDE M.R. , MARDZINOVÁ S. , ČURLIK J. , ŠPANELOVÁ D.
Published: November 2006

Abstract:  Serological examination of humans in Slovakia suspected of having rickettsial infections revealed the presence of antibodies to spotted fever group rickettsiae (R. conorii, R. slovaca, and R. typhi). Of interest is the finding of serological positivity to the newly recognized “IRS” agent. Antibodies to these rickettsiae and to C. burnetii were demonstrated also in domestic and hunting dogs and pet animals. These results confirm the occurrence and possible circulation of these rickettsiae and C. burnetii in the Slovak Republic.
Corpuscular Antigenic Microarray for the Serodiagnosis of Blood Culture–Negative Endocarditis
Authors: SAMSON LAURENT , DRANCOURT MICHEL , CASALTA JEAN‐PAUL , RAOULT DIDIER
Published: November 2006

Abstract:  Blood culture–negative endocarditis is due to fastidious bacteria, including Coxiella burnetii and Bartonella spp. Diagnosis of such infection relies on serology and microimmunofluorescence is therefore the reference method. We developed a multiplex serology test featuring automatic incubation and reading and incorporating internal controls. Preliminary results indicate that this new serologic test is valuable for the rapid, automated serological diagnosis of blood culture–negative endocarditis.
Diagnosis of Coxiella burnetii Pericarditis Using a Systematic Prescription Kit in Case of Pericardial Effusion
Authors: LEVY P.Y. , THUNY F. , HABIB G. , BONNET J.L. , DJIANE P. , RAOULT D.
Published: November 2006

Abstract: 
Coxiella burnetii, regarded as a potential agent of pericarditis, wa found to be responsible for almost 5% of the cases of idiopathic pericardial effusion reported in this series. Diagnosis was aided by use of a systematic kit described in this paper.
Human Coxiella burnetii Infections in Regions of Bosnia and Herzegovina, 2002
Authors: ŠUKRIJA ZVIZDIĆ , HAMZIĆ SADETA , ČENGIĆ DŽEVAD , BEŠLAGIĆ EDINA , FEJZIĆ NIHAD , ČOBANOV DARKO , MAGLAJLIĆ JASMINKA , PUVAČIĆ SANDRA , PUVAČIĆ ZLATKO
Published: November 2006

Abstract:  Acute infections in humans and animals caused by Coxiella burnetii (C. burnetii) are becoming an important medical problem for Bosnia and Herzegovina (B&H). From a clinical and epidemiological aspect, Q fever represents a complex medical problem, considering that one of the highest incidence rates of Q fever in Europe has been recorded during the last few years in B&H. The first case of this disease in B&H was described in 1950, by Muray et al., and the first epidemic, with 16 infected individuals, was recorded the same year. Confirmed animal infections by C. burnetii in B&H were first reported in 1985 when, of all tested sheep, positive results were found in 12.4%. During 2001, 2.11% of tested sheep and goats were found to have a positive result, which was also confirmed by studies from the following years in particular regions of B&H. These studies suggest that endemic loci of infected animals are established in particular geographic regions in B&H, which is important to emphasize for better understanding of the sources and routes of C. burnetii transmission to the human population. This conclusion is based on the studies from 2000, when 2.17% of positive cattle, 1.85% of positive sheep, and 0.27% of positive goats were registered. During the same period, in B&H, in 6 different regions, 156 individuals with Q fever were registered as were 3 separate epidemics with 115 infected individuals. Official data on the number of detected animal C. burnetii infections during 2002 suggest that 10 positive cattle and 88 positive sheep or goats were registered. During 2003, 24 positive cattle, 29 positive goats, and 167 positive sheep were detected, while in 2004, 71 positive cattle, 4 positive goats, 37 positive sheep, and 72 positive animals from the sheep–goat group were registered. According to official reports from 2001, 19 individuals with Q fever were registered in B&H, while in 2002, the number of infected individuals increased to 250. In five cantons in B&H, 43 infected individuals were registered during 2002, while in Republika Srpska of B&H, 207 infected individuals in the region of Banja Luka were registered. From 1998 to 2003, 373 individuals with Q fever were reported in B&H, whereof 265 individuals (71.04%) were infected during epidemics, and 108 (28.95%) sporadically. Q fever incidence rates in B&H were high during 1998 (5.68%ooo) and very high in 2000, with 115 individuals with an acute clinical form and an incidence rate of 6.95%ooo. The incubation time varied between 9 and 28 days.
The Foci of Scrub Typhus and Strategies of Prevention in the Spring in Pingtan Island, Fujian Province
Authors: HENGBIN GUO , MIN CAO , KAIHUA TAO , JIAQI TANG
Published: November 2006

Abstract:  This study investigates the foci of tsutsugamushi disease on Pingtan Island, China, with emphasis on cases of illness that occur in the spring. The investigation of the physical and medical geography in the endemic area and detection of 141 sera samples in the population of Pingtan Island is described. The serum samples were taken from 102 soldiers and 39 residents and were tested by the indirect immunofluorescence assay. An island resident's history of illness inquiry was also conducted, and the results are discussed. We were able to determine the most prevalent types of rats and mites from the rat bodies. We isolated the DNA from the spleen of 40 rats and from five groups of mites by polymerase chain reaction. Orientia tsutsugamushi was isolated by perctoneally injecting KM mice with the patient's untreated blood along with ground rat viscera (R. losea) and ground mites (L. deliense), respectively. The isolates were typed at the molecular level. This study will then present direct prevention strategies that emphasize personal hygiene, methods of personal protection, keeping living environments clean, and it will provide strategies to eliminate rats and mites. As a result of adopting these strategies, no case of scrub typhus occurred in this region in approximately 2003–2004.
Evaluation of E. ruminantium Genes in DBA/2 Mice as Potential DNA Vaccine Candidates for Control of Heartwater
Authors: SIMBI BIGBOY H. , BOWIE MICHAEL V. , McGUIRE TRAVIS C. , BARBET ANTHONY F. , MAHAN SUMAN M.
Published: November 2006

Abstract:  Heartwater caused by the rickettsia Ehrlichia ruminantium (E. ruminantium) is an acute and fatal tick‐borne disease of domestic and some wild ruminants. A user‐friendly vaccine does not exist. We selected and tested nine genes of E. ruminantium for protection against challenge in a DBA/2 mouse model, in order to identify candidate genes for incorporation into a recombinant vaccine. Of the nine DNA vaccine constructs tested, four DNA constructs 14HWORF1/VR1012, 14HWORF2/VR1012, 27HWORF1/VR1012, and HSP58/VR1012 were not protective and were excluded from the study. The remaining five DNA constructs—MAP2/ VR1012, 1HWORF3/ VR1012, 4HWORF1/ VR1012, 18HWORF1/ VR1012, and 3GDORF3/ VR1012—offered partial protection against lethal challenge demonstrated by reduced mortalities compared to control groups. Protection was augmented when DNA primed mice were boosted with a respective homologous recombinant protein. Protection in these five groups was associated with the induction of cell‐mediated or T helper 1 (Th1) type of immune responses characterized by the production of large amounts of interferon‐gamma and interleukin‐2 in in vitro proliferation assays using E. ruminantium antigens for stimulation. These responses were enhanced when the DNA‐vaccinated DBA/2 mice were boosted with specific homologous recombinant protein vaccination. In a preliminary follow‐up study, protection conferred by DNA vaccination with individual gene constructs was not enhanced when the protective constructs were administered in combination (including the map‐1 gene of E. ruminantium). Further evaluation of these and other untested DNA constructs is necessary to optimize their expression in vivo in the presence of molecular adjuvants, such as the IFN‐gamma gene, GM‐CSF gene, IL‐12 gene, and CpG motifs to fully evaluate their protective value.
Experimental Infections in Dogs with Ehrlichia canis Strain Borgo 89
Authors: JOURET‐GOURJAULT STÉPHANIE , PARZY DANIEL , DAVOUST BERNARD
Published: November 2006

Abstract:  This study attemps to clarify the virulence and the pathogenicity of the Borgo 89 strain of Ehrlichia canis isolated from a sick dog in Corsica (France). Four unscathed beagles were intravenously injected with an inoculum of leukocytes infected with the Borgo 89 strain and the animals were examined daily for clinical signs of disease, and blood samples were drawn at frequent intervals for biochemical and hematologic assessment. Serologic (IFI) and PCR assays were also carried out. The results at autopsy are presented in this paper, leading to the conclusion that the Borgo 89 strain has a pathogenicity comparable to that of the known strains. However, the discovery of a case of completely unapparent infection raises the question of a possible individual immunization whose origin remains unexplained.
Changes in Attentional Performance of Children and Young Adults With Localized Primary Brain Tumors After Conformal Radiation Therapy
Authors: Kiehna Erin N. , Mulhern Raymond K. , Li Chenghong , Xiong Xiaoping , Merchant Thomas E.
Published: November 2006

Purpose

To prospectively assess the impact of conformal radiation therapy (CRT) and demographic and clinical variables on four measures of attention in pediatric and young adult patients with localized primary brain tumors.

Patients and Methods

We prospectively evaluated 120 patients with primary brain tumors, ages 2 to 24.4 years (median, 9.2 years). Evaluations were done using the computerized Conners' Continuous Performance Test (CCPT). We analyzed errors of omission (inattentiveness), errors of commission (impulsivity), reaction time, and an overall index of performance before CRT, weekly during CRT, and serially up to 60 months after the start of CRT.

Results

Before CRT, patients exhibited mild inattentiveness. During CRT, impulsivity decreased significantly (P = .002). After CRT, inattentiveness increased significantly (P = .03), and global attention disorders were associated with craniopharyngioma (P < .0001), supratentorial tumors (P = .008), optic pathway and diencephalic tumors (P = .012), and subtotal resection of the tumor (P = .010).

Conclusion

Brain tumors and their treatment impair sustained attention and reaction time. A decline in impulsivity and relative stability of the other CCPT scores over the course of CRT demonstrated the absence of early radiation-related cognitive sequelae. Local tumor effects, initial surgical intervention, and focal irradiation of central structures contribute to long-lasting attentional problems in pediatric and young adult patients.
Identification of Tumor-Specific Molecular Signatures in Intracranial Ependymoma and Association With Clinical Characteristics
Authors: Modena Piergiorgio , Lualdi Elena , Facchinetti Federica , Veltman Joris , Reid James F. , Minardi Simone , Janssen Irene , Giangaspero Felice , Forni Marco , Finocchiaro Gaetano , Genitori Lorenzo , Giordano Flavio , Riccardi Riccardo , Schoenmakers Eric F.P.M. , Massimino Maura , Sozzi Gabriella
Published: November 2006

Purpose

To delineate clinically relevant molecular signatures of intracranial ependymoma.

Materials and Methods

We analyzed 24 primary intracranial ependymomas. For genomic profiling, microarray-based comparative genomic hybridization (CGH) was used and results were validated by fluorescent in situ hybridization and loss of heterozygosity mapping. We performed gene expression profiling using microarrays, real-time quantitative reverse transcriptase polymerase chain reaction, and methylation analysis of selected genes. We applied class comparison analyses to compare both genomic and expression profiling data with clinical characteristics.

Results

A variable number of genomic imbalances were detected by array CGH, revealing multiple regions of recurrent gain (including 2q23, 7p21, 12p, 13q21.1, and 20p12) and loss (including 5q31, 6q26, 7q36, 15q21.1, 16q24, 17p13.3, 19p13.2, and 22q13.3). An ependymoma-specific gene expression signature was characterized by the concurrent abnormal expression of developmental and differentiation pathways, including NOTCH and sonic hedgehog signaling. We identified specific differentially imbalanced genomic clones and gene expression signatures significantly associated with tumor location, patient age at disease onset, and retrospective risk for relapse. Integrated genomic and expression profiling allowed us to identify genes of which the expression is deregulated in intracranial ependymoma, such as overexpression of the putative proto-oncogene YAP1 (located at 11q22) and downregulation of the SULT4A1 gene (at 22q13.3).

Conclusion

The present exploratory molecular profiling study allowed us to refine previously reported intervals of genomic imbalance, to identify novel restricted regions of gain and loss, and to identify molecular signatures correlating with various clinical variables. Validation of these results on independent data sets represents the next step before translation into the clinical setting.
Plasma Osteopontin Is an Independent Prognostic Marker for Head and Neck Cancers
Authors: Petrik David , Lavori Philip W. , Cao Hongbin , Zhu Yonghua , Wong Priscilla , Christofferson Erin , Kaplan Michael J. , Pinto Harlan A. , Sutphin Patrick , Koong Albert C. , Giaccia Amato J. , Le Quynh-Thu
Published: November 2006

Purpose

To confirm the relationship between plasma osteopontin (OPN) levels and treatment outcomes in head and neck squamous cell carcinoma (HNSCC) patients in an expanded study.

Patients and Methods

One hundred forty patients with newly diagnosed HNSCC were enrolled onto this study, 54 previously reported and 86 new patients. Pretreatment plasma OPN levels were assessed in all patients by an enzyme-linked immunosorbent assay method. OPN levels were correlated to treatment outcomes in the new group of patients. Detailed analyses were also performed on the relationship between OPN and tumor control rate, event-free survival (EFS), and postrelapse survival for the entire group.

Results

Using a previously defined cut off point of 450 ng/mL, there was a significant correlation between OPN and freedom-from-relapse (P = .047), overall survival (P = .019), and EFS (P = .023) in the new, independent patient cohort (n = 86). Sequence of event analyses using the entire group (N = 140) revealed that OPN was an independent prognostic factor for initial tumor control, EFS in those who have achieved tumor control, and postrelapse survival.

Conclusion

In this expanded study, we were able to replicate the prognostic significance of OPN using a predefined cut off point in an independent patient group and demonstrated that plasma OPN is an independent prognostic marker for HNSCC.
Phase II Study of Consolidation Paclitaxel After Concurrent Chemoradiation in Poor-Risk Stage III Non–Small-Cell Lung Cancer: SWOG S9712
Authors: Davies Angela M. , Chansky Kari , Lau Derick H.M. , Leigh Bryan R. , Gaspar Laurie E. , Weiss Geoffrey R. , Wozniak Antoinette J. , Crowley John J. , Gandara David R.
Published: November 2006

Purpose

A previous Southwest Oncology Group (SWOG) study (S9429) demonstrated efficacy and tolerability of concurrent chemoradiotherapy in poor-risk stage III non–small-cell lung cancer (NSCLC). This study evaluated adding consolidation paclitaxel after chemoradiotherapy for a similar patient cohort.

Patients and Methods

Patients with histologically/cytologically determined stage III NSCLC were eligible based on performance status (PS) 2 and either low albumin or weight loss more than 10%, poor pulmonary function, or comorbidities precluding cisplatin use. Treatment was carboplatin 200 mg/m2 days 1, 3, 29, and 31, and etoposide 50 mg/m2 days 1 through 4, and 29 to 32. Beginning day 1, thoracic radiation was delivered at 1.8 Gy in 25 fractions plus 16-Gy boost (total dose, 61 Gy). Patients without disease progression received paclitaxel 175 mg/m2 every 21days for three cycles.

Results

Characteristics of 87 eligible patients were age 51 to 82 years; 57% PS 0 to 1, 43% PS 2; and 51% stage IIIA, 49% stage IIIB. Toxicities of concurrent chemoradiotherapy included grade 3 esophagitis (7%) and grade 3/4 neutropenia (43%). Fifty-four assessable patients received paclitaxel consolidation. Four treatment-related deaths occurred during chemoradiotherapy and four occurred during consolidation. Overall response rate was 53%. Median progression free- and overall survival were 6.1 and 10.2 months, respectively. One- and 2-year survival rates were 43% and 25%.

Conclusion

Compared with a previous SWOG trial in a similar patient population, the addition of consolidation paclitaxel after chemoradiotherapy resulted in increased toxicity without a survival advantage. More PS 2 patients (43% v 18%) enrolled onto S9712, which may explain increased toxicity and lack of benefit. The optimal chemoradiotherapy approach for poor-risk patients remains to be defined.
Multicenter Phase II Study of Irinotecan, Cisplatin, and Bevacizumab in Patients With Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Authors: Shah Manish A. , Ramanathan Ramesh K. , Ilson David H. , Levnor Alissa , D'Adamo David , O'Reilly Eileen , Tse Archie , Trocola Robin , Schwartz Lawrence , Capanu Marinela , Schwartz Gary K. , Kelsen David P.
Published: November 2006

Purpose

Bevacizumab improves survival in several solid tumor malignancies when combined with chemotherapy. We evaluated the efficacy and safety of the addition of bevacizumab to chemotherapy in the treatment of gastric and gastroesophageal junction (GEJ) adenocarcinoma.

Patients and Methods

Forty-seven patients with metastatic or unresectable gastric/GEJ adenocarcinoma were treated with bevacizumab 15 mg/kg on day 1, irinotecan 65 mg/m2, and cisplatin 30 mg/m2 on days 1 and 8, every 21 days. The primary end point was to demonstrate a 50% improvement in time to progression over historical values. Secondary end points included safety, response, and survival.

Results

Patient characteristics were as follows: median age 59 years (range, 25 to 75); Karnofsky performance status 90% (70% to 100%); male:female, 34:13; and gastric/GEJ, 24:23. With a median follow-up of 12.2 months, median time to progression was 8.3 months (95% CI, 5.5 to 9.9 months). In 34 patients with measurable disease, the overall response rate was 65% (95% CI, 46% to 80%). Median survival was 12.3 months (95% CI, 11.3 to 17.2 months). We observed no increase in chemotherapy related toxicity. Possible bevacizumab-related toxicity included a 28% incidence of grade 3 hypertension, two patients with a gastric perforation and one patient with a near perforation (6%), and one patient with a myocardial infarction (2%). Grade 3 to 4 thromboembolic events occurred in 25% of patients. Although the primary tumor was unresected in 40 patients, we observed only one patient with a significant upper gastrointestinal bleed.

Conclusion

Bevacizumab can be safely given with chemotherapy even with primary gastric and GEJ tumors in place. The response rate, time to disease progression (TTP), and overall survival are encouraging, with TTP improved over historical controls by 75%. Further development of bevacizumab in gastric and GEJ cancers is warranted.
Treatment‐resistant OCD, inflated responsibility, and the therapeutic relationship: Two case examples
Authors: Kohlenberg Robert J. , Vandenberghe Luc
Published: November 2006

This paper is about the use of an unconventional intervention for treatment‐resistant OCD that we describe as ‘Therapist Assumes Responsibility’ (TAR). The use of TAR in this paper as a clinical treatment parallels an experimental analysis by Lopatka and Rachman (1995). Two case studies are used to illustrate TAR and the use of the therapist‐client relationship in the treatment of OCD. These include learning to trust others and accepting reasonable levels of insecurity. It is proposed that the addition of an interpersonal factor to CBT theories of OCD helps to explain the role of inflated responsibility and how the client‐therapist relationship can be used during treatment. It is further proposed that reassurance seeking might also be the result of this same interpersonal factor.
Development of a Stress Corrosion Cracking Test Methodology Using Tube-shaped Specimens
Authors: Sato Yasumoto , He Xue , Takeda Yoichi , Shoji Tetsuo
Published: November 2006

Stress corrosion cracking (SCC) is one of the greatest concerns in nuclear aging and degradation, and studies on the measurement of stress corrosion crack growth rates (CGR) and the effects of environmental, material, and mechanical parameters on the CGR have been performed using mainly fracture mechanics specimens. However, the stress states for the fracture mechanics specimens are different from that of real field components and there is concern about the applicability of the data obtained from fracture mechanics specimens to the evaluation of SCC behaviors in real field components. In this study, in order to obtain SCC for specimens that have a similar shape of real field components under complicated stress states, an SCC test methodology using specimens in the shape of tubes was developed. Its effectiveness was verified by performing an SCC test using a mock-up of a bottom mount instrumentation tube of a pressurized water reactor (PWR) under a simulated PWR primary water environment. Intergranular SCC was created in the mock-up specimen using the developed SCC test methodology and SCC crack growth rate for the mock-up specimen was measured.
The Breviari d'Amor: Rhetoric and Preaching in Thirteenth-Century Languedoc
Authors: Bolduc Michelle
Published: November 2006

Abstract Altough little known in medieval history, the Breviari d'Amor of Matfre Ermengaud was deeply influenced by medieval preaching. An Occitan encyclopaedia, the Breviari includes a short guide to preaching, entitled “De predicacio et en quel manieira deu hom predicar” which derives from the Cura pastoralis of Gregory the Great. “De predicacio” is no mere translation, but a subtle adaptation: it indicates not only how the Breviari is aimed toward lay education in the popular language, but also to what point it responds to its historic and religious context. This study, therefore, considers the Breviari as a text deeply engaged in the matter of preaching in Languedoc at the end of the thirteenth century.
Countable filters on ω
Authors: Spinas Otmar
Published: November 2006

Two countable filters on ω are incompatible if they have no common infinite pseudointersection. Letting (Pf) denote the minimal size of a maximal uncountable family of pairwise incompatible countable filters on ω, we prove the consistency of t < a(Pf).
The distribution of properly Σ20 e-degrees
Authors: Bereznyuk Stanislaw , Coles Richard , Sorbi Andrea
Published: November 2006

We show that for every enumeration degree a < 0′e there exists an e-degree c such that a ≤ c < 0′e, and all degrees b, with c ≤ b < 0′e, are properly Σ20.
Closures in ℵ0-categorical bilinear maps
Authors: Baudisch Andreas
Published: November 2006

It is possible to define a combinatorial closure on alternating bilinear maps with few relations similar to that in [2]. For the ℵ0-categorical case we show that this closure is part of the algebraic closure.
Ordinal diagrams for Π3-reflection
Authors: Arai Toshiyasu
Published: November 2006

In this paper we introduce a recursive notation system O(Π3) of ordinals. An element of the notation system is called an ordinal diagram. The system is designed for proof theoretic study of theories of Π3-reflection. We show that for each α < Ω in O(Π3) a set theory KP Π3 for Π3-reflection proves that the initial segment of O(Π3) determined by α is a well ordering. Proof theoretic study for such theories will be reported in [ 4].
Classification of δ-invariant amalgamation classes
Authors: Aref'ev Roman D. , Baldwin John T. , Mazzucco Marco
Published: November 2006

Hrushovski's generalization of the Fraisse construction has provided a rich source of examples in model theory, model theoretic algebra and random graph theory. The construction assigns to a dimension function δ and a class K of finite (finitely generated) models a countable ‘generic’ structure. We investigate here some of the simplest possible cases of this construction. The class K will be a class of finite graphs; the dimension, δ(A), of a finite graph A will be the cardinality of A minus the number of edges of A. Finally and significantly we restrict to classes which are δ-invariant. A class of finite graphs is δ-invariant if membership of a graph in the class is determined (as specified below) by the dimension and cardinality of the graph, and dimension and cardinality of all its subgraphs. Note that a generic graph constructed as in Hrushovski's example of a new strongly minimal set does not arise from a δ-invariant class.

We show there are countably many δ-invariant (strong) amalgamation classes of finite graphs which are closed under subgraph and describe the countable generic models for these classes. This analysis provides ω-stable generic graphs with an array of saturation and model completeness properties which belies the similarity of their construction. In particular, we answer a question of Baizhanov (unpublished) and Baldwin [5] and show that this construction can yield an ω-stable generic which is not saturated. Further, we exhibit some ω-stable generic graphs that are not model complete.
On the Origin of Green Emission Bands in Fluorene‐Based Conjugated Polymers
Authors: Montilla F. , Mallavia R.
Published: November 2006

Blue‐light‐emitting diodes made of polyfluorenes have low stability and, under operation, rapidly degrade and produce undesirable low‐energy emission bands (green or g‐bands). A spectroelectrochemical study of the degradation process suffered by polyfluorenes is reported here. These polymers lose their electronic properties by electrochemical oxidation and reduction through σ‐bond breaking. In addition, upon electrochemical reduction, the development of a structured green emission band at 485 nm is observed. The position and shape of this band is different from the usual featureless band at 535 nm assigned to fluorenone defects. The green‐light‐emitting product is isolated and analyzed by Fourier‐transform IR spectroscopy; fluorenone formation is excluded. The isolated product is crosslinked; its green emission is probably related to the formation of an intramolecular excimer.
Efficiency penalty analysis for pure H2 production processes with CO2 capture
Authors: Feng Wei , Ji Peijun , Tan Tianwei
Published: November 2006

The conventional steam‐reforming (CSR) process is a major process for the production of pure hydrogen from natural gas with CO2 as the main by‐product. In this work, based on the CSR process, several alternative H2‐producing processes with CO2 capture are simulated and analyzed. The alternative processes capture the CO2 by concentrating the CO2 through the approaches including burning some of the separated H2 instead of CH4 in the furnace, using pure oxygen instead of air for the combustion of fuel gas, applying a prereformer to reduce the usage of pure oxygen, and applying an H2‐membrane in the steam reformer to separate pure H2. The reactors of the CSR process and the alternative processes with CO2 capture were simulated based on the kinetic models of the reactions. The CSR process and the alternative processes were evaluated in terms of the thermodynamic efficiency, the amount of high pressure (HP) H2 produced per mole of CH4, the amount of CO2 produced per mole of HP H2, and the CO2 captured per mol of HP H2. The efficiency penalties for CO2 capture of the alternative processes were compared and discussed. © 2006 American Institute of Chemical Engineers AIChE J, 2007
CFD and experimental study on methane hydrate dissociation Part I. Dissociation under water flow
Authors: Sean Wu‐Yang , Sato Toru , Yamasaki Akihiro , Kiyono Fumio
Published: November 2006

Dissociation processes of methane hydrate under water flow conditions were investigated by a combination of experimental observations and numerical simulations using computational fluid dynamics (CFD). In Part I of this study, the dissociation process induced by water flow at pressures above the three‐phase [hydrate (H)–liquid water (Lw)–vapor (V)] boundary in an isothermal x–P phase diagram is discussed. Dissociation experiments were carried out with a methane hydrate ball (diameter ≅ 10 mm) suspended in a flow cell, and the overall dissociation rate of methane hydrate without bubble formation was measured under various conditions of pressure, temperature, and volumetric flow rate of water. A linear phenomenological rate equation in the form of the product of the dissociation rate constant kbl and the molar Gibbs free energy difference ΔG, between the hydrate phase and the ambient aqueous phase, was derived by considering the Gibbs free energy difference as the driving force for the dissociation. The molar Gibbs free energy difference was expressed by the logarithm of the ratio of the concentration of methane dissolved in water at the hydrate surface to the solubility of methane in the aqueous solution in equilibrium with the hydrate. The dissociation rate constant kbl was determined from the experimental results of the overall dissociation rate combined with the numerical simulation results of the concentration profile of methane by the CFD method. The obtained dissociation rate constant was found to be independent of the ambient water flow rate, indicating that the rate constant is intrinsic for the hydrate dissociation within the conditions examined in this study. The rate constant was independent of the pressure, whereas the temperature dependency was described by an Arrhenius‐type equation with the apparent activation energy of 98.3 kJ/mol. © 2006 American Institute of Chemical Engineers AIChE J, 2007
Titelbild: Oxetanes as Promising Modules in Drug Discovery (Angew. Chem. 46/2006)
Authors: Wuitschik Georg , Rogers‐Evans Mark , Müller Klaus , Fischer Holger , Wagner Björn , Schuler Franz , Polonchuk Liudmila , Carreira Erick M.
Published: November 2006

Der Oxetanring ist ein wenig beachteter Heterocyclus in der medizinischen Chemie. In ihrer Zuschrift auf S. 7900 ff. zeigen M. Rogers‐Evans, E. M. Carreira et al., dass dieses Strukturmotiv wichtige physiko‐ und pharmakochemische Eigenschaften eines zugrunde liegenden Gerüstes verbessern kann. In einer Serie lipophiler tertiärer Aminderivate wurde ein “Oxetan‐Scan” durchgeführt, um den Einfluss des Oxetanrings auf ausgewählte Verbindungseigenschaften zu testen.
Use of cell bleed in a high cell density perfusion culture and multivariable control of biomass and metabolite concentrations
Authors: Deschênes J‐S. , Desbiens A. , Perrier M. , Kamen A.
Published: November 2006

A main problem in controlling bioprocesses is the lack of manipulated variables. Batches and fed‐batches cannot be drained of the waste substances produced by the biomass. A chemostat (CSTR) may have the dilution rate as the manipulated variable, allowing a certain control over the biomass concentration with a risk, however, of washout if the dilution rate gets higher than the maximum growth rate. Perfusion processes with full biomass retention are somewhat similar to batches, as no steady state is really obtained until biomass growth is stopped by nutrient limitations. Cell bleed is often used in perfusions to improve the overall cell culture viability, and prevent accumulation of dead cells. However, use of the cell bleed stream as a manipulated variable for control has not yet received much attention. This paper's main contribution is the use of cell bleed as an additional degree of freedom in a multivariable control strategy for a perfusion culture. To add to the originality of the contribution, the control strategy used is multivariable nonlinear adaptive backstepping, which has never been used for a perfusion bioreactor. Results show a good performance of the controller, while the chosen set points actually correspond to perfusion operation. Copyright © 2006 Curtin University of Technology and John Wiley & Sons, Ltd.
Study of the bread oven rise by on‐line image analysis
Authors: Bai X. , Zhou W.
Published: November 2006

The final volume of a bread loaf is determined by a fast and dynamic phenomenon during baking, called ‘oven rise’. This paper describes a method to characterize the bread oven‐rise pattern by on‐line image analysis. The bread baking process was acquired on‐line as a series of digital images by a camera. The images were then processed to extract the morphological feature of the bread to enable the calculation of bread volume, based on the assumed geometry. Changes in the bread volume were found to exhibit a three‐stage pattern. Influences of the dough mixing time and a novel ingredient, green tea extract (GTE), were examined from the patterns. Copyright © 2006 Curtin University of Technology and John Wiley & Sons, Ltd.
Optimal operation of baker's yeast fermentation in the presence of uncertainty
Authors: Vemuri Jyothy , Palanki Srinivas
Published: November 2006

In this paper, we consider the problem of determining the optimal feeding policy for a fed‐batch fermentation for the production of baker's yeast in the presence of uncertainty. Two algorithms are discussed for computing the optimal solution in the presence of uncertainty. The first method is a measurement‐based closed‐loop approach where process measurements are utilized to make on‐line adjustments to the optimization routine. The second method is a simulator‐based open‐loop approach where simulations are run assuming various operating policies, and utilizing the simulator as if it were the real process. These two methods are implemented on a baker's yeast fermentation with uncertain parameters, and it is shown that both approaches lead to improved performance over the conventional open‐loop operation. Copyright © 2006 Curtin University of Technology and John Wiley & Sons, Ltd.