bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune challenge affects sexual coloration of male Iberian wall lizards
Authors: López Pilar , Gabirot Marianne , Martín José
Published: October 2008

Sexual signals can be evolutionarily stable if they are honest and condition dependent or costly to the signaler. One possible cost is the existence of a trade‐off between maintaining the immune system and the elaboration of ornaments. We experimentally challenged the immune system of male Iberian wall lizards, Podarcis hispanica, with a bacterial antigen (lipopolysaccharide) without pathogenic effects to explore whether the immune activation affected sexually dimorphic visual ornaments. Ventrolateral coloration changed in all males, but immune activation affected some characteristics of coloration of experimental males (i.e., challenged males failed to increase brightness and medium wavelengths over time as control males did, and the proportion of yellow pigments decreased after the immune activation) but not others (i.e., proportion of blue, green and red pigments changed equally in all males). Results suggested the existence of a trade‐off between physiological regulation of the immune system and the allocation of essential compounds (probably carotenoids) to sexual ornaments. We suggest that this trade‐off may allow one to honestly signal individual male quality via characteristics of coloration in lizards, which may have an important role in both intra‐ and intersexual selection processes. J. Exp. Zool. 311A:96–104, 2009. © 2008 Wiley‐Liss, Inc.
β‐keratins of the crocodilian epidermis: composition, structure, and phylogenetic relationships
Authors: Dalla Valle Luisa , Nardi Alessia , Gelmi Carlotta , Toni Mattia , Emera Deena , Alibardi Lorenzo
Published: October 2008

Nucleotide and deduced amino acid sequences of three β‐keratins of Nile crocodile scales are presented. Using 5′‐ and 3′‐RACE analysis, two cDNA sequences of 1 kb (Cr‐gptrp‐1) and 1.5 kb (Cr‐gptrp‐2) were determined, corresponding to 17.4 and 19.3 kDa proteins, respectively, and a pI of 8.0. In genomic DNA amplifications, we determined that the 5′‐UTR of Cr‐gptrp‐2 contains an intron of 621 nucleotides. In addition, we isolated a third gene (Cr‐gptrp‐3) in genomic DNA amplifications that exhibits seven amino acid differences with Cr‐gptrp‐2. Genomic organization of the sequenced crocodilian β‐keratin genes is similar to avian β‐keratin genes. Deduced proteins are rich in glycine, proline, serine, and tyrosine, and contain cysteines toward the N‐ and C‐terminal regions, likely for the formation of disulfide bonds. Prediction of the secondary structure suggests that the central core box of 20 amino acids contains two β‐strands and has 75–90% identity with chick β‐keratins. Toward the C‐terminus, numerous glycine–glycine–tyrosine and glycine–glycine–leucine repeats are present, which may contribute to making crocodile scales hard. In situ hybridization shows expression of β‐keratin genes in differentiating β‐cells of epidermal transitional layers. Phylogenetic analysis of the available archosaurian and lepidosaurian β‐keratins suggests that feather keratins diversified early from nonfeather keratins, deep in archosaur evolution. However, only the complete knowledge of all crocodilian β‐keratins will confirm whether feather keratins have an origin independent of those in bird scales, which preceded the split between birds and crocodiles. J Exp Zool (Mol. Dev. Evol.) 312B:42–57, 2009. © 2008 Wiley‐Liss, Inc.
New method to deliver exogenous material into developing planarian embryos
Authors: Martín‐Durán José María , Duocastella Martí , Serra Pere , Romero Rafael
Published: October 2008

The ability to report or modify the embryological processes in living embryos is pivotal for developmental biology research. Planarian embryology has experienced renewed interest as the genetic pathways that drive adult regeneration were found to be involved in the development of embryos. The major drawback to the study of planarian embryology is the absence of methods that give access to the embryos and enable their manipulation. Herein, we report on a novel method for delivering external material into developing embryos using nanosecond laser pulses. When focused on the eggshell surface under optimal parameters, laser pulses ablate the protective case and open a pathway throughout which foreign material can be delivered. In this study, we used egg capsules from Schmidtea polychroa (Schmidt, 1861) to microinject 1 µm fluorescein isothiocyanate fluorescent beads into the live embryos. We obtained viability values ranging from 15% in early egg capsules to 100% in late developmental stages. Moreover, we measured the delivery effectiveness as the number of hatchlings containing fluorescent beads per microinjected egg capsule, reaching 100% in early stages and almost 40% in late stages. This is the first time that planarian embryos have been modified without compromising normal development. We consider that this technique will be of extreme value to future work on planarian developmental biology and regeneration, enabling the application of modern functional tools to the study of this Lophotrochozoan. J. Exp. Zool. (Mol. Dev. Evol.) 310B:668–681, 2008. © 2008 Wiley‐Liss, Inc.
Aid allocation to fragile states: Absorptive capacity constraints
Authors: Feeny Simon , McGillivray Mark
Published: October 2008

The international donor community has grave concerns about the effectiveness of aid to countries it classifies as ‘fragile states’. The impact of aid on growth and poverty reduction and the ability to efficiently absorb additional inflows is thought to be significantly lower in these countries compared to other recipients. This paper examines this issue and suggests that a while a number of fragile states can efficiently absorb more aid than they have received, a number receive far more aid than they can efficiently absorb from a perspective based purely on per capita income growth. Policy recommendations are provided. Copyright © 2008 John Wiley & Sons, Ltd.
Argentine hemorrhagic fever diagnostic test based on recombinant Junín virus N protein
Authors: Ure Agustín E. , Ghiringhelli P. Daniel , Possee Robert D. , Morikawa Shigeru , Romanowski Víctor
Published: October 2008

Junín arenavirus is the etiologic agent of Argentine hemorrhagic fever. Due to its morbidity and high mortality rate in untreated cases, this endemic disease is of mandatory report in Argentina. Secure and accurate diagnostic methods are needed for the epidemiological surveillance of the disease. Current assays rely on antigens prepared from lysates of virus infected mammalian cells. The bio‐safety issue related to the manipulation of large quantities of virus restricts such antigen production to laboratories with the appropriate containment facilities. In this report, we describe the development of an enzyme linked immunosorbent assay for the etiologic confirmation of the disease, based on recombinant antigens expressed in insect cells. Eight different variables of the assay were optimized with the Taguchi approach for experimental design (L18 design, seven three‐level factors and one two‐level factor). The area under the receiver operating characteristics (ROC) curve was 0.966, showing the high accuracy of the test discriminating positive from negative samples. Taking into account the biosafety benefits, the high yields of antigen in cell culture, and the general performance of the assay, it is expected that it will be a useful alternative to the current ELISA for the detection of antibodies in sera from convalescent patients. J. Med. Virol. 80:2127–2133, 2008. © 2008 Wiley‐Liss, Inc.
A wide spectrum of dengue IgM and PCR positivity post‐onset of illness found in a large dengue 3 outbreak in Pakistan
Authors: Tang Julian W. , Khanani Muhammad R. , Zubairi Adnan M. , Lam Wai Y. , Lai Florence , Hashmi Khursheed , Hussain Arif , Jamal Saba , Chan Paul K.S.
Published: October 2008

During a large outbreak of dengue serotype 3 in Pakistan in 2006, multiple serum samples were routinely collected for laboratory testing. Two hundred ninety‐seven samples were collected between August and November 2006. Serological testing for dengue IgM was performed in Pakistan and polymerase chain reaction (PCR) testing for dengue RNA detection and serotyping were performed in Hong Kong. Dengue‐specific IgM was detectable as early as 1 day, and dengue RNA remained detectable for up to 14 days, post‐onset of illness. Further statistical analysis found that IgM status (positive, negative, or equivocal) was significantly correlated to clinical (duration of illness, severity of patient‐reported arthralgia pain, the presence of any evidence of bleeding, a positive tourniquet test, shock), and other laboratory (platelet and total white cell counts) parameters. In contrast, the qualitative dengue RNA status (PCR positive or negative) was not statistically significantly correlated with any of these other parameters. The results for this population during this outbreak, obtained from single acute samples, demonstrate a wide range of intervals post‐onset of illness during which dengue IgM and dengue RNA may be detected. Interestingly, in this study, the dengue IgM positivity correlates more closely with significant clinical illness than the dengue RNA positivity, which may be a feature specific to this particular outbreak. J. Med. Virol. 80:2113–2121, 2008. © 2008 Wiley‐Liss, Inc.
Identification of a novel human papillomavirus type 16 E1 gene variant with potentially reduced oncogenicity
Authors: Sabol Ivan , Matovina Mihaela , Gasperov Nina Milutin , Grce Magdalena
Published: October 2008

The human papillomavirus (HPV) 16 genome has been studied extensively, although no study has focused on the E1 gene that is implicated in viral DNA replication. After analyzing the E1 region of HPV 16 genomes in 429 cervical samples, 11.2% were found to contain a 63 nucleotides duplication in this region. Sequence analysis of the E6 and the E7 regions has shown that all samples containing this duplication were related to E6‐G350 variant of the HPV 16 (Chi square test, P = 0.0012). A comparison of cervical lesion severity of the examinees having regular or variant E1 genes has shown that the variant group had a significantly (Fischer's exact test, P = 0.0401) lower percentage of high grade disease cases, suggesting that this particular duplication might reduce the oncogenic potential of HPV 16, and also might clarify the differences of E6‐G350 variant oncogenicity observed in European populations. Albeit, a decreased incidence of high grade cervical lesions can be linked to the prevalence of multiple HPV infection, the additional decrease of those cases with the variant E1 gene versus those without (10.5% and 18.6%, respectively) can only be ascribed to the effect of this particular HPV variant. Further research is needed to clarify the biology of these HPV 16 E1 variants. J. Med. Virol. 80:2134–2140, 2008. © 2008 Wiley‐Liss, Inc.
Presence and expression of JCV early gene large T Antigen in the brains of immunocompromised and immunocompetent individuals
Authors: Delbue Serena , Branchetti Emanuela , Boldorini Renzo , Vago Luca , Zerbi Pietro , Veggiani Claudia , Tremolada Sara , Ferrante Pasquale
Published: October 2008

JC virus (JCV) is a polyomavirus that asymptomatically infects up to 80% of the worldwide human population and establishes latency in the kidney. In the case of host immunodeficiency, it can cause progressive multifocal leukoencephalopathy (PML), which is a fatal demyelinating disease of the central nervous system. In an attempt to understand better PML pathogenesis and JCV infection, the presence of the JCV genome and expression of the early viral protein in the brain of deceased individuals, with and without HIV infection, was investigated. Sixty autopsy samples of brain tissues were collected from 15 HIV‐positive PML patients, 15 HIV‐positive patients with other neurological diseases, 15 HIV‐positive patients without neurological disorders, and 15 HIV‐negative individuals who died from diseases unrelated to the central nervous system. By means of specific Real Time Polymerase Chain Reaction, the JCV genome was detected in 14 of 15 PML brains, three of 15 HIV‐positive brains (with and without neurological diseases), and 1 of 15 HIV‐negative brains. JCV genotyping was also performed. Expression of the early JCV protein T Antigen was verified by a specific immunohistochemistry assay, and it was found in the brain tissues from 12 PML cases and one case with other neurological disease. The data obtained demonstrate that infection of the brain with JCV can also be observed in the brains of HIV‐negative individuals, without neurological disorders. However, viral protein expression was limited to PML brains and to one brain from a patient with other neurological disease, suggesting that JCV can also be present in the brains of patients without PML. J. Med. Virol. 80:2147–2152, 2008. © 2008 Wiley‐Liss, Inc.
Titration of hepatitis B virus infectivity in the sera of pre‐acute and late acute phases of HBV infection: Transmission experiments to chimeric mice with human liver repopulated hepatocytes
Authors: Tabuchi Ayako , Tanaka Junko , Katayama Keiko , Mizui Masaaki , Matsukura Harumichi , Yugi Hisao , Shimada Takashi , Miyakawa Yuzo , Yoshizawa Hiroshi
Published: October 2008

Studies of hepatitis B virus (HBV) infection in non‐human primates such as chimpanzees are no longer possible due to ethical considerations and the endangered status of chimpanzees since April 2007 in Japan. A human hepatocyte transplanted chimeric mouse was used to characterize HBV infectivity in serial stages of acute infection. Chimeric mice were inoculated intravenously with serum samples obtained from an experimentally infected chimpanzee with HBV. Sera from the pre‐acute phases (i.e., rump‐up viremia prior to anti‐HBc) and late acute phases (i.e., declining phase of HBsAg and anti‐HBcAb positive) were collected from the chimpanzees 57 and 244 days after inoculation. These sera contained 2.6 × 106 and 2.8 × 106 copies/ml of HBV DNA, respectively. Three chimeric mice inoculated intravenously with 100 µl of pre‐acute serum (equivalent to 100 copy of HBV DNA) developed an HBV infection. The three chimeric mice that received 100 µl of pre‐acute serum (equivalent to 101 copies of HBV DNA), developed high levels of serum HBV DNA. None of the three chimeric mice inoculated with 100 µl of 1:104 dilution (equivalent to 101 copies of HBV DNA) of late‐acute serum was infected, while only one of three chimeric mice inoculated with 100 µl of 1:103 dilution (equivalent to 102 copies of HBV DNA) of late‐acute serum developed an HBV infection. Based on these results, chimeric mice can be used as animal models for the study of HBV infectivity, pathogenesis and control. The results show that pre‐acute phase HBV serum is about 100‐times more infectious than late acute phase serum. J. Med. Virol. 80:2064–2068, 2008. © 2008 Wiley‐Liss, Inc.
Molecular epidemiology of hepatitis delta virus (HDV) in Iran: A preliminary report
Authors: Mohebbi Seyed Reza , Zali Narges , Derakhshan Faramarz , Tahami Ali , Mashayekhi Reza , Amini‐Bavil‐Olyaee Samad , Zali Mohammad Reza
Published: October 2008

To identify hepatitis delta virus (HDV) genetic variability and its circulating genotypes amongst infected Iranian patients, 25 patients with positive anti‐HDV status from different parts of Iran were enrolled in this cross‐sectional study. A portion of the HDV delta antigen was amplified, sequenced, and subjected to molecular and phylogenetic analysis. Clinical features and virological markers were evaluated. HDV RNA could be detected in 88% of anti‐HDV positive cases (22 patients) with chronic hepatitis B virus (HBV) infection and liver cirrhosis. Phylogenetic analysis revealed that all Iranian patients were infected by genotype I (clade 1) of HDV, supported by a high bootstrap value (100%, 1,000 replicates). All HDV‐positive patients were coinfected with genotype D1 of HBV. No significant association was determined between demographic, clinical, and virological variables in the population studied. In conclusion, the present molecular epidemiology survey reveals that clade 1 of HDV is predominant among coinfected HBV patients in Iran. J. Med. Virol. 80:2092–2099, 2008. © 2008 Wiley‐Liss, Inc.
Quantification of BK polyoma viruria in Japanese children and adults with hemorrhagic cystitis complicating stem cell transplantation
Authors: Tanaka Kaori , Hori Tsukasa , Hatakeyama Naoki , Yamamoto Masaki , Takayama Rumiko , Yoto Yuko , Suzuki Nobuhiro , Hayashi Toshiaki , Ikeda Yukiho , Ikeda Hiroshi , Ishida Tadao , Tsutsumi Hiroyuki
Published: October 2008

Polyoma BK virus (BKV) is frequently found in the urine of stem cell transplantation (SCT) patients with hemorrhagic cystitis (HC), but also occurs in SCT patients without HC. How BK viruria relates to the development of HC in SCT patients, especially in children, has not yet been fully evaluated. In the present study, we analyzed the relationship of several factors including urinary BKV load to HC development in children and adults undergoing SCT. We employed a quantitative PCR assay and evaluated 37 patients (aged 9 months–62 years) of whom 12 developed HC and 25 did not. Older age was a risk factor for the development of HC; however, other factors such as sex, primary disease, type of SCT, conditioning regimen and aGVHD were not. Peak urinary BKV values in HC patients were not higher than those in non‐HC patients. Severity of HC also did not correlate with urinary BKV loads. However, in some patients who secreted higher urinary BKV loads, the peak loads were closely related with the onset of HC. Higher BKV loads may be a risk factor for the development of HC in conjunction with other coexisting factors. J. Med. Virol. 80:2108–2112, 2008. © 2008 Wiley‐Liss, Inc.
PL‐100, a novel HIV‐1 protease inhibitor displaying a high genetic barrier to resistance: An in vitro selection study
Authors: Dandache Serge , Coburn Craig A. , Oliveira Maureen , Allison Timothy J. , Holloway M. Katharine , Wu Jinzi J. , Stranix Brent R. , Panchal Chandra , Wainberg Mark A. , Vacca Joseph P.
Published: October 2008

The development of new HIV inhibitors with distinct resistance profiles is essential in order to combat the development of multi‐resistant viral strains. A drug discovery program based on the identification of compounds that are active against drug‐resistant viruses has produced PL‐100, a novel potent protease inhibitor (PI) that incorporates a lysine‐based scaffold. A selection for resistance against PL‐100 in cord blood mononuclear cells was performed, using the laboratory‐adapted IIIb strain of HIV‐1, and it was shown that resistance appears to develop slower against this compound than against amprenavir, which was studied as a control. Four mutations in protease (PR) were selected after 25 weeks: two flap mutations (K45R and M46I) and two novel active site mutations (T80I and P81S). Site‐directed mutagenesis revealed that all four mutations were required to develop low‐level resistance to PL‐100, which is indicative of the high genetic barrier of the compound. Importantly, these mutations did not cause cross‐resistance to currently marketed PIs. In contrast, the P81S mutation alone caused hypersensitivity to two other PIs, saquinavir (SQV) and nelfinavir (NFV). Analysis of p55Gag processing showed that a marked defect in protease activity caused by mutation P81S could only be compensated when K45R and M46I were present. These data correlated well with the replication capacity (RC) of the mutant viruses as measured by a standard viral growth assay, since only viruses containing all four mutations approached the RC of wild type virus. X‐ray crystallography provided insight on the structural basis of the resistance conferred by the identified mutations. J. Med. Virol. 80:2053–2063, 2008. © 2008 Wiley‐Liss, Inc.
Antiviral effect of human saliva against hantavirus
Authors: Hardestam Jonas , Petterson Lisa , Ahlm Clas , Evander Magnus , Lundkvist Åke , Klingström Jonas
Published: October 2008

Hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome are zoonotic diseases caused by rodent borne hantaviruses. Transmission to humans occurs usually by inhalation of aerozolized virus‐contaminated rodent excreta. Although human‐to‐human transmission of Andes hantavirus has been observed, the mode of transmission is currently not known. Saliva from Puumala hantavirus (PUUV)‐infected patients was shown recently to contain viral RNA. To test if human saliva interferes with hantavirus replication, the effect of saliva and salivary proteins on hantavirus replication was studied. It was observed that saliva from healthy individuals reduced Hantaan hantavirus (HTNV) infectivity, although not completely. Furthermore, HTNV was resistant against the antiviral capacity of histatin 5, lysozyme, lactoferrin, and SLPI, but was inhibited by mucin. Inoculation of bank voles (Myodes glareolus) with HFRS‐patient saliva, positive for PUUV‐RNA, did not induce sero‐conversion. In conclusion, no evidence of infectious virus in patient saliva was found. However, the in vitro experiments showed that HTNV, the prototype hantavirus, is insensitive to several antiviral salivary proteins, and is partly resistant to the antiviral effect of saliva. It therefore remains to be shown if human saliva might contain infectious virions early during infection, that is, before seroconversion. J. Med. Virol. 80:2122–2126, 2008. © 2008 Wiley‐Liss, Inc.
High frequency of rotavirus viremia in children with acute gastroenteritis: Discordance of strains detected in stool and sera
Authors: Chitambar Shobha D. , Tatte Vaishali S. , Dhongde Ram , Kalrao Vijay
Published: October 2008

Recently, rotavirus antigenemia and viremia have been identified in patients with acute gastroenteritis. This study examined rotavirus viremia in children hospitalized for acute gastroenteritis in order to establish its association with fecal shedding of rotavirus, infecting genotypes and antibody marker of acute infection. Thirty‐one pairs of stool–serum specimens were collected from November 2004 to February 2005 together with clinical information. All paired specimens were screened for rotavirus RNA by RT‐PCR using the VP6 gene primers. All stool and serum specimens were tested for rotavirus antigen and anti‐rotavirus IgM respectively by ELISA. Sixteen of 31 stool–serum pairs showed the presence of rotavirus RNA. Nine stool and two serum specimens were positive only by RT‐PCR. The total positivity in rotavirus RNA was significantly higher in both stools (80.6%) and sera (58.1%) than that of stool antigen (38.7%) and anti‐rotavirus IgM (25.8%) (P < 0.01). All PCR positive paired specimens were typed for the VP7 (G) and VP4 (P) genes. Five of sixteen pairs could be typed for both genes. Three of the five pairs showed concordance (G2P[4]/G2P[4]) while two showed discordance (G12P[8]/G2P[4], G8P[4]/G2P[4]) in the genotypes detected in stool and serum specimens respectively. The study documents a high frequency of rotavirus viremia in patients with acute diarrhea. The discordance of rotavirus strains at the genotypic level in the serum and stool of individual patients with diarrhea suggests the susceptibility of extra‐intestinal sites for rotavirus infection and the possibility of differential dissemination of rotavirus strains from the intestine. J. Med. Virol. 80:2169–2176, 2008. © 2008 Wiley‐Liss, Inc.
Bracketing team boundary spanning: An examination of task‐based, team‐level, and contextual antecedents
Authors: Joshi Aparna , Pandey Niti , Han Guohong (Helen)
Published: October 2008

There is growing recognition that teams do not function in a vacuum and that external boundary activities are important predictors of team performance, effectiveness, and knowledge sharing. In the past, researchers have focused on the effects of team composition or task characteristics as antecedents of critical boundary spanning activities. However, less effort has been directed at understanding how antecedents at multiple levels can simultaneously influence boundary spanning behavior in teams. This paper takes stock of over 20 years of research on the topic of team boundary spanning. Adopting a “bracketing” approach etc., we develop a multi‐level theoretical model to guide future research on the determinants of team boundary spanning. This model specifies task‐based, team‐level, and contextual antecedents of team boundary spanning and outlines the contingencies shaping the emergence of effective boundary‐management behavior in teams. Copyright © 2008 John Wiley & Sons, Ltd.
Soil organic carbon–stock changes in Flemish grassland soils from 1990 to 2000
Authors: Mestdagh Inge , Sleutel Steven , Lootens Peter , Van Cleemput Oswald , Beheydt Daan , Boeckx Pascal , De Neve Stefaan , Hofman George , Van Camp Nancy , Vande Walle Inge , Samson Roeland , Verheyen Kris , Lemeur Raoul , Carlier Lucien
Published: October 2008

Total soil organic‐carbon (SOC) stocks for grassland soils in Flanders (N Belgium) were determined for the Kyoto Protocol reference year 1990 and 2000 in order to investigate whether these soils have been CO2 sinks or sources during that period. The stocks were calculated by means of detailed SOC datasets, which were available at the community scale for the whole of Flanders. The total SOC stocks for Flemish grassland soils (1 m depth) were estimated at 38 Mt SOC in 1990 and 34 Mt SOC in 2000. The loss of SOC resulted from a decrease in the SOC content of grassland soils (71%) and could also partly (29%) be explained by a decline in grassland area. Significant decreases in %SOC for the 0–6 cm depth layer were found for the 1990s for the coarser‐textured soils with SOC losses ranging between –0.3% and –0.5% over the 10 y period. Specific management practices that disturb the SOC balance such as conversion to temporary grassland and a reduction of animal‐manure application are hypothesized to have contributed to the observed loss of SOC stocks. We furthermore conducted an analysis of uncertainty of the 1990 and 2000 grassland SOC–stocks calculation using Monte Carlo analysis. Probability‐distribution functions were determined for each of the inputs of the SOC‐stock calculation, enabling us to assess the uncertainty on the 1990 and 2000 SOC stocks. The frequency distributions of these simulated stocks both closely approached lognormal distributions, and their 95%‐confidence intervals ranged between 150% and 50% of the calculated mean SOC stock. The standard error on the measured decrease in SOC stocks in Flemish grassland soils during the 1990s was calculated to be 7–8 Tg SOC, which is equivalent to twice this decrease. This clearly shows that large‐scale changes in SOC stocks are uncertainty‐ridden, even when they are based on detailed datasets.
Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): Early results of RTOG 0132/ACRIN 6665
Authors: Eisenberg Burton L. , Harris Jonathan , Blanke Charles D. , Demetri George D. , Heinrich Michael C. , Watson James C. , Hoffman John P. , Okuno Scott , Kane John M. , von Mehren Margaret
Published: October 2008

Background

Therapy for gastrointestinal stromal tumors (GIST) has changed significantly with the use of imatinib mesylate (IM). Despite the success of this drug in metastatic GIST, disease progression remains a perplexing clinical issue suggesting the need for multimodality management. There have been no prospective studies either evaluating the neoadjuvant use of IM in primary GIST or as a preoperative cytoreduction agent for metastatic GIST.

Methods

RTOG 0132/ACRIN 6665 was a prospective phase II study evaluating safety and efficacy of neoadjuvant IM (600 mg/day) for patients with primary GIST or the preop use of IM in patients with operable metastatic GIST. The trial continued postop IM for 2 years.

Results

Sixty‐three patients were entered (52 analyzable), 30 patients with primary GIST (Group A) and 22 with recurrent metastatic GIST (Group B). Response (RECIST) in Group A was (7% partial, 83% stable, 10% unknown), in Group B (4.5% partial, 91% stable, 4.5% progression). Two‐year progression free survival (Group A 83%, Group B 77%). Estimated overall survival (Group A 93%, Group B 91%). Complications of surgery and IM toxicity were minimal.

Conclusion

This trial represents the first prospective report of preop IM in GIST. This approach is feasible, requires multidisciplinary consultations, and is not associated with notable postop complications. J. Surg. Oncol. 2009;99:42–47. © 2008 Wiley‐Liss, Inc.
Malignant abdominal mesothelioma: Defining the role of surgery
Authors: Rodríguez Dayron , Cheung Michael C. , Housri Nadine , Koniaris Leonidas G.
Published: October 2008

Objective

Determine the role of surgery for patients with malignant abdominal mesotheliomas (MAMs).

Methods

The Surveillance, Epidemiology, and End Results (SEER) database (1973–2005) was queried.

Results

Overall, 10,589 cases of malignant mesotheliomas were identified. Of these, 9,211 cases were thoracic (TM) and 1,112 cases were MAM (10.5%). Patients with TM presented with more localized disease than those patients with MAM (P < 0.001). MAM more often affected younger patients (63 years vs. 71 years) (P < 0.001). The annual incidence of MAM was approximately 1.00 case per 100,000 in 2005. Overall median survival for MAM patients was 8 months, with a significant difference between women and men (13 months vs. 6 months, respectively) (P < 0.001). Patients who successfully underwent surgical resection had a considerably longer median survival (20 months vs. 4 months, P < 0.001) as well as a significantly higher 5‐year survival (28% vs. 12%, P < 0.001). Multivariate analysis identified that a poorly differentiated tumor grade, failure to undertake surgical resection, advanced age, and male gender were all independent predictors of poorer outcome.

Conclusion

Surgical extirpation of MAM may be associated with significantly improved survival. All patients with MAM should be evaluated for potential surgical resection. J. Surg. Oncol. 2009;99:51–57. © 2008 Wiley‐Liss, Inc.
Validation of SPE‐HPLC determination of 1,4‐benzodiazepines and metabolites in blood plasma, urine, and saliva
Authors: Nasir Uddin Mohammad , Samanidou Victoria F. , Papadoyannis Ioannis N.
Published: October 2008

A simple, sensitive, selective, and reproducible RP‐HPLC method with DAD detection at 240 nm was developed for the determination of six 1,4‐benzodiazepines: bromazepam (BRZ), clonazepam (CLZ), diazepam (DZP), flunitrazepam (FNZ), lorazepam (LRZ), alprazolam (APZ); and two metabolites: α‐hydroxyalprazolam (HALZ) and α‐hydroxytriazolam (HTZL) in human plasma, urine, and saliva, using colchicine as internal standard, after SPE using Nexus Varian cartridges. Separation was performed on a Kromasil C8 (250 mm×5 mm, 5 μm) analytical column with a gradient mobile phase containing methanol, ACN and 0.05 M ammonium acetate. Linearity was held within the range 0.3–20.0 ng/μL, with coefficients of determination (r2) better than 0.997. The within‐ and between‐day assay RSD at 2, 4, 8 ng/μL ranged from 0.03 to 4.7% and 0.5 to 7.0%, respectively in standards, from 1.3 to 7.9% and 3.3 to 7.3%, respectively in plasma, from 2.1 to 6.0% and 2.1 to 7.8%, respectively in urine and at 0.5, 1.0, 2.0 ng/μL ranged from 2.22 to 5.8% and 2.2 to 8.1%, respectively, in saliva. The mean relative recoveries were 96.3–108.6, 96.0–108.2, 94.3–107.1, 97.0–107.0% in within‐day assay and 96.8–107.7, 94.6–107.6, 93.2–105.8, 96.0–108.6 in between‐day assay for standard, plasma, urine, and saliva, respectively. The LOD and LOQ were 0.02–0.47 and 0.07–1.57 ng/μL, respectively.
Determination of quinolone antibiotics in urine by capillary electrophoresis with chemiluminescence detection
Authors: Liu Yan‐Ming , Jia Yu‐Xiu , Tian Wei
Published: October 2008

A novel and simple method is presented for the determination of norfloxacin, ciprofloxacin, and ofloxacin by capillary electrophoresis with chemiluminescence detection. This method is based on the enhancing effect of quinolones on the chemiluminescence reaction of the Ce(SO4)2–Ru(bpy)32+–HNO3 system. Three quinolones were successfully separated and detected under optimum conditions. The obtained detection limits were 2.3×10–7 mol/L, 5.2×10–8 mol/L, and 7.8×10–8 mol/L for ciprofloxacin, norfloxacin, and ofloxacin, respectively. The RSD of migration time and peak area were less than 1.8 and 3.8% (n = 5), respectively. The applicability of the proposed method was illustrated in the determination of ofloxacin in eye drops and of norfloxacin in human urine samples, and the monitoring of pharmacokinetics for norfloxacin.
HPLC quantification of dye flavonoids in Reseda luteola L. from Portugal
Authors: Moiteiro Cristina , Gaspar Helena , Rodrigues Ana I. , Lopes João F. , Carnide Valdemar
Published: October 2008

A HPLC method was developed for the simultaneous identification of Reseda luteola L. (weld) flavonoids and quantification of the main compounds responsible for the yellow color. This method was applied to a large number of wild Portuguese weld to evaluate its potential application as dyestuff for textile factories, as a substitute for the synthetic dyes currently used. Portuguese weld dyestuff content ranged between 1.04 and 5.87%, corresponding to a wide variation of the flavonoids amount (1.39–9.04%). Luteolin 4′‐O‐glucoside was found for the first time in R. luteola, but kaempferol, isorhamnetin, and their glycosides were not detected in the Portuguese specimens.
An Easy Strategy for the Synthesis of Well‐Defined Aliphatic‐Aromatic Hyperbranched Polyesters
Authors: Schallausky F. , Erber M. , Komber H. , Lederer A.
Published: October 2008

A one‐pot solution polymerization under mild conditions was adapted for the synthesis of well‐defined aliphatic‐aromatic polyesters with different degrees of branching. The esterification was performed at room temperature using 4,4‐bis(4′‐hydroxyphenyl)valeric acid (AB2) and 3‐(4‐hydroxyphenyl)propionic acid (AB) as monomers. DPTS was used as a catalyst and DCC as a coupling agent. Polyesters with statistical, dendritic topology, controlled degree of branching and $\overline M _{\rm w}$ > 35 000 g · mol−1 were obtained. The polymers were characterized by 1H and 13C NMR, SEC, DSC, and TGA. A strong dependence of the degree of branching and the thermal properties of the polymers depending on the AB/AB2 monomer ratio was observed.

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Some remarks on global existence to the Cauchy problem of the wave equation with nonlinear dissipation
Authors: Amroun Nour‐Eddine , Benaissa Abbès
Published: October 2008

In this paper we prove the existence of global decaying H2 solutions to the Cauchy problem for a wave equation with a nonlinear dissipative term by constructing a stable set in H1(ℝn ). (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Curves without plane model of small degree
Authors: Keem Changho , Martens Gerriet
Published: October 2008

Let C be a smooth irreducible projective curve of genus g > 0 and sC (2) the minimal degree of plane models of C. Clearly, sC (2) ≤ g + 2. Our main result is: sC (2) = g + 2 – t (for some integer t ≥ 0) implies that C is a double cover of a curve of genus at most t provided that g is not too small with respect to t. For small t we can be more precise. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On the geometry of orthonormal frame bundles
Authors: Kowalski Oldřich , Sekizawa Masami
Published: October 2008

In this paper we are studying the geometry of orthonormal frame bundles over Riemannian manifolds, which are equipped, as submanifolds of the full frame bundles, by the induced Sasaki–Mok metric. All kinds of curvatures are calculated and many geometric results are proved. It seems that the geometry of the orthogonal frame bundles is much more interesting (and more “flexible”) than that of the general frame bundles studied earlier by L. A. Cordero and M. de León. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Regioregular Poly(3‐hexylthiophene) in a Novel Conducting Amphiphilic Block Copolymer
Authors: Craley C. Rockford , Zhang Rui , Kowalewski Tomasz , McCullough Richard D. , Stefan Mihaela C.
Published: October 2008

Regioregular poly(3‐hexylthiophene) has been successfully incorporated into a novel amphiphilic block copolymer. The amphiphilic nature of poly(3‐hexylthiophene)‐block‐poly(acrylic acid) has been investigated using spectroscopic methods and has yielded solvatochromic behavior in several solvents of varying polarity. Evidence suggests that a supramolecular, long range ordering of block copolymer occurs in polar solvents, resulting in the formation of aggregates. Despite relatively large amounts of non‐conductive blocks, the poly(3‐hexylthiophene) diblock copolymer yields a high conductivity of 1 S · cm−1, and atomic force microscopy shows the formation of a highly organized nanofibrilar morphology in the solid state.

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Phosphorus Ligands for Iron(III)‐Mediated Atom Transfer Radical Polymerization of Methyl Methacrylate
Authors: Xue Zhigang , Oh Hyun Sook , Noh Seok Kyun , Lyoo Won Seok
Published: October 2008

The iron(III)‐catalyzed atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) was successfully employed using tributylphosphine (TBP) and trimethylphosphite (TMP) as ligands in the absence of a reducing agent. The effects of solvent and initiator on polymerization of MMA were investigated. Most of the polymerizations with these ligands were well controlled with a linear increase in the number average molecular weights ($\overline M _{\rm n}$) versus conversion and relatively low molecular weight distribution ($\overline M _{\rm w} /\overline M _{\rm n}$ = 1.2–1.4) throughout the reactions, and the measured weights matched with the predicted values. The ethyl 2‐bromoisobutyrate (EBriB) initiated ATRP of MMA with the FeBr3/TBP or FeBr3/TMP catalytic system was better controlled in toluene than in the other solvents used in this study at 80 °C.

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Grafted Polymer Chains Interacting with Substrates: Computer Simulations and Scaling
Authors: Descas Radu , Sommer Jens‐Uwe , Blumen Alexander
Published: October 2008

We review scaling methods and computer simulations used in the study of the static and dynamic properties of polymer chains tethered to adsorbing surfaces under good solvent conditions. By varying both the grafting density and the monomer/surface interactions a variety of phases can form. In particular, for attractive interactions between the chains and the surface the classical mushroom‐brush transition known for repulsive substrates splits up into an overlap transition and a saturation transition which enclose a region of semidilute surface states. At high grafting densities oversaturation effects and a transition to a brush state can occur. We emphasize the role of the critical adsorption parameters for a correct description and understanding of such polymer adsorption phenomena.

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Beyond HCF – Is there a fatigue limit?
Authors: Berger C. , Pyttel B. , Schwerdt D.
Published: October 2008

The paper gives an overview to the present state of research on fatigue strength and failure mechanisms at very high number of cycles (N>107). Testing facilities are listed. A classification of materials with typical S‐N curves and influencing factors like notches, residual stresses and environment are given. Different failure mechanisms, which occur especially in the VHCF‐region like subsurface failure, are explained. There microstructural inhomogeneities and statistical conditions play an important role. Investigated materials are different metals with body‐centred cubic lattice like low‐ or high‐strength steels and quenched and tempered steels but also materials with a face‐centred cubic lattice like aluminium alloys and copper.
Influence of porosity and environmental impact on fatigue life of magnesium alloys
Authors: Heuler P. , Grimm J. , Fuhrmann K. , Troßmann T. , Eulitz K.‐G.
Published: October 2008

Based on experimental investigations using specimens with different grades of porosity, a significant influence of the material condition of die‐cast magnesium alloys on the accuracy of fatigue‐life estimation according to the local‐strain approach is verified if the data‐base is not related to the microstructure of the component. In order to address this transferability issue, a porosity‐depending formulation is proposed. Based on a sensitivity analysis, a simplified, empirical engineering approach has been derived that describes the effect of the inherent porosity on fatigue strength via the fatigue‐strength exponent b. Furthermore, it is shown that the degradation of the fatigue‐behaviour in chloride‐containing media is not simply determined by the external corrosive attack, but also influenced by inner defects competing with the environmental impact.
Approaches for fatigue assessment of welded joints in automotive industry
Authors: Greuling S.
Published: October 2008

The numerical fatigue assessment of seam welded joints is of significant importance in automotive industry. In order to use the fatigue concepts, which are available in the literature, in series calculations, they usually have to be implemented into commercial software programmes. In the following contribution the possibilities available are discussed with respect to the needs in automotive industry. No specific commercial software will be discussed in detail. At the end open questions for developments necessary in the future will be addressed.
Service fatigue design of complex welded construction equipment
Authors: Samuelsson J. , Jonsson B. , Barsoum Z.
Published: October 2008

Many steel structures and components are fabricated from steel plates and steel castings. The dominating joining method is welding for all kinds of transport vehicles and this paper describes briefly main problems in connection with design and fabrication of fatigue loaded structures. Design and fabrication has developed during the last 30 years and today we have tools, methods and knowledge to produce more optimised structures. Some of the work has been performed as joint work within Nordic projects and within IIW (International Institute of Welding). FE‐modelling, improved design rules, knowledge about influence from defects and residual stresses, new manufacturing methods and scientific based weld quality rules are briefly discussed in this paper.
Characterization of an alternatively spliced GADD45α, GADD45α1 isoform, in arsenic‐treated epithelial cells
Authors: Zhang Yadong , Beezhold Kevin , Castranova Vince , Shi Xianglin , Chen Fei
Published: October 2008

A new GADD45α isoform, GADD45α1, was identified in the cellular response to arsenic. DNA sequencing and biochemical analyses suggested that GADD45α1 is derived from an alternative splicing of the GADD45α mRNA by skipping the region corresponding to exon2 of the gadd45α gene during mRNA maturation. In addition to the size difference due to the lack of 34 amino acids encoded by exon2, GADD45α1 and GADD45α proteins differ in their effects on cell proliferation and cell cycle transition. Unlike GADD45α, the GADD45α1 is unable to attenuate cell growth. In over‐expression experiments, the full length GADD45α, but not the GADD45α1, sensitized cells to arsenic‐induced prometaphase arrest of the cell cycle. Furthermore, GADD45α1 appears to be able to antagonize the function of the GADD45α on the G2/M phase cell cycle arrest as demonstrated in cotransfection experiment. Thus, these data suggest that the generation of the GADD45α1 isoform may not only offset but also antagonize the effects of arsenic and GADD45α on cell growth and cell cycle regulation. © 2008 Wiley‐Liss, Inc.
Down‐regulation of the microRNAs miR‐34a, miR‐127, and miR‐200b in rat liver during hepatocarcinogenesis induced by a methyl‐deficient diet
Authors: Tryndyak Volodymyr P. , Ross Sharon A. , Beland Frederick A. , Pogribny Igor P.
Published: October 2008

Altered expression of microRNAs (miRNAs) has been reported in diverse human cancers; however, the down‐regulation or up‐regulation of any particular miRNAs in cancer is not sufficient to address the role of these changes in carcinogenesis. In this study, using the rat model of liver carcinogenesis induced by a methyl‐deficient diet, which is relevant to the hepatocarcinogenesis in humans associated with viral hepatitis C and B infections, alcohol exposure and metabolic liver diseases, we showed that the development of hepatocellular carcinoma (HCC) is characterized by prominent early changes in expression of miRNA genes, specifically by inhibition of expression of microRNAs miR‐34a, miR‐127, miR‐200b, and miR‐16a involved in the regulation of apoptosis, cell proliferation, cell‐to‐cell connection, and epithelial‐mesenchymal transition. The mechanistic link between these alterations in miRNAs expression and the development of HCC was confirmed by the corresponding changes in the levels of E2F3, NOTCH1, BCL6, ZFHX1B, and BCL2 proteins targeted by these miRNAs. The significance of miRNAs expression dysregulation in respect to hepatocarcinogenesis was confirmed by the persistence of these miRNAs alterations in the livers of methyl‐deficient rats re‐fed a methyl‐adequate diet. Altogether, the early occurrence of alterations in miRNAs expression and their persistence during the entire process of hepatocarcinogenesis indicate that the dysregulation of microRNAs expression may be an important contributing factor in the development of HCC. © 2008 Wiley‐Liss, Inc.
Epidermal growth factor receptor and claudin‐2 participate in A549 permeability and remodeling: Implications for non‐small cell lung cancer tumor colonization
Authors: Peter Yakov , Comellas Alejandro , Levantini Elena , Ingenito Edward P. , Shapiro Steven D.
Published: October 2008

Tumor colonization involves changes in cell permeability and remodeling. Paracellular permeability is regulated by claudins, integrated tight junction (TJ) proteins, located on the apicolateral portion of epithelial cells. Epidermal growth factor (EGF) was reported to modify cellular claudin levels and induce remodeling. To investigate a role for EGF receptor (EGFR) activation in tumor colonization we studied the effect of EGF and claudin‐2 overexpression on permeability and cell reorganization in the human A549 non‐small cell lung cancer (NSCLC) cell line. Our data demonstrated that A549 cells possess functional TJs and that EGF treatment increased levels of claudin‐2 expression by 46%. Furthermore, EGFR signaling reduced monolayer permeability to choline and triggered cellular remodeling. The mitogen‐activated protein kinase inhibitor PD98059 blocked the effect on A549 permeability and remodeling. EGF stimulation also exacerbated a fourfold increase in cell colonization elicited by claudin‐2 upregulation. Our findings are consistent with the hypothesis that EGFR signaling plays an important role in A549 cell physiology and acts synergistically with claudin‐2 to accelerate tumor colonization. Understanding the influence of EGF on A549 cell permeability and reorganization will help shed light on NSCLC tumor colonization and contribute to the development of novel anti‐cancer treatments. © 2008 Wiley‐Liss, Inc.