PathogenMip Assay: A Multiplex Pathogen Detection Assay

The Molecular Inversion Probe (MIP) assay has been previously applied to a large-scale human SNP detection. Here we describe the PathogenMip Assay, a complete protocol for probe production and applied approaches to pathogen detection. We have demonstrated the utility of this assay with an initial set of 24 probes targeting the most clinically relevant HPV genotypes associated with cervical cancer progression. Probe construction was based on a novel, cost-effective, ligase-based protocol. The assay was validated by performing pyrosequencing and Microarray chip detection in parallel experiments. HPV plasmids were used to validate sensitivity and selectivity of the assay. In addition, 20 genomic DNA extracts from primary tumors were genotyped with the PathogenMip Assay results and were in 100% agreement with conventional sequencing using an L1-based HPV genotyping protocol. The PathogenMip Assay is a widely accessible protocol for producing and using highly discriminating probes, with experimentally validated results in pathogen genotyping, which could potentially be applied to the detection and characterization of any microbe

Distribution Patterns of Infection with Multiple Types of Human Papillomaviruses and Their Association with Risk Factors

Background: Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1, 810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. Principal Findings: The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (-31.1%), or were of mestizo (-24.6%) or black (-40.9%) ethnicity. Conclusions: According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2-4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.This project was funded by Asociacion Investigacion Solidaria SADAR, Caja Navarra (Navarra, Spain) and the Spanish Agency for International Development Cooperation (AECID) (Project 08-CAP2-0609)

Dendritic Cell Based Tumor Vaccination in Prostate and Renal Cell Cancer: A Systematic Review and Meta-Analysis

BACKGROUND: More than 200 clinical trials have been performed using dendritic cells (DC) as cellular adjuvants in cancer. Yet the key question whether there is a link between immune and clinical response remains unanswered. Prostate and renal cell cancer (RCC) have been extensively studied for DC-based immunotherapeutic interventions and were therefore chosen to address the above question by means of a systematic review and meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Data was obtained after a systematic literature search from clinical trials that enrolled at least 6 patients. Individual patient data meta-analysis was performed by means of conditional logistic regression grouped by study. Twenty nine trials involving a total of 906 patients were identified in prostate cancer (17) and RCC (12). Objective response rates were 7.7% in prostate cancer and 12.7% in RCC. The combined percentages of objective responses and stable diseases (SD) amounted to a clinical benefit rate (CBR) of 54% in prostate cancer and 48% in RCC. Meta-analysis of individual patient data (n = 403) revealed the cellular immune response to have a significant influence on CBR, both in prostate cancer (OR 10.6, 95% CI 2.5-44.1) and in RCC (OR 8.4, 95% CI 1.3-53.0). Furthermore, DC dose was found to have a significant influence on CBR in both entities. Finally, for the larger cohort of prostate cancer patients, an influence of DC maturity and DC subtype (density enriched versus monocyte derived DC) as well as access to draining lymph nodes on clinical outcome could be demonstrated. CONCLUSIONS/SIGNIFICANCE: As a 'proof of principle' a statistically significant effect of DC-mediated cellular immune response and of DC dose on CBR could be demonstrated. Further findings concerning vaccine composition, quality control, and the effect of DC maturation status are relevant for the immunological development of DC-based vaccines

Korrosionsverhalten MIG-geschweisster Verbindungen an hoeherfesten Aluminiumlegierungen Abschlussbericht

The corrosion behavior of the Alloys AA 6013 and AA 6056 - and for comparison also AA 6181 - in a welded condition was investigated. The higher grade alloyed S-AlMg_4, 5MnZr and S-AlSi_5 alloys were used as welding filler alloys. During corrosion test procedures the following results were obtained: In standardized laboratory investigations (EXCO test, salt spray test, alternate immersion test) low pitting corrosion or intergranular corrosive action occurred in the base alloy independent of the type of alloy. The welding deposit and heat influence remained free of any corrosive attack independent of the welding filler alloy used. During stress crack corrosion investigations of flat tensile specimens by means of lever arm load application, no corrosive action was detected for any of the alloy pairs investigated. Electrochemical laboratory investigations (potentiodynamic, potentiostatic) in artificial sea water indicated a better corrosion resistance of the welding deposit and heat influence zone than the respective base alloy, independent of the base alloy under investigation. Informal oscillatory corrosion tests (alternate bending tests) in air and artificial sea water showed no significant differences between the alloy pairs tested. Natural tests under field exposure on Sylt and at Zinnwald indicated that the alloys tested and their welds barely have been subject to corrosive action after approximately one year of exposure. (orig./MM)Es wurde das Korrosionsverhalten der Werkstoffe AA 6013 und AA 6056 - zum Vergleich zusaetzlich AA 6181 - im geschweissten Zustand untersucht. Als Schweisszusatzwerkstoffe wurden die hoeherlegierten Legierungen S-AlMg4, 5MnZr und S-AlSi5 angewendet. Bei den Korrosionspruefverfahren wurden folgende Ergebnisse erzielt: Bei genormten Laborkorrosionsuntersuchungen (EXCO-Test, Salzspruehnebeltest, Wechseltauchversuch) trat geringer Lochfrass- bzw. interkristalliner Korrosionsangriff im Grundwerkstoff unabhaengig von der Legierungsart auf. Schweissgut und Waermeeinfluss blieben unabhaengig vom verwendeten Schweisszusatzwerkstoff frei von einem Korrosionsangriff. Bei Spannungsrisskorrosionsuntersuchungen an Flachzugproben mittels Hebelarmbelastung wurde bei keiner der untersuchten Werkstoffpaarungen ein Korrosionsangriff festgestellt. Elektrochemische Laboruntersuchungen (potentiodynamisch, potentiostatisch) in kuenstlichem Meerwasser erbrachten eine bessere Korrosionsbestaendigkeit von Schweissgut und Waermeeinflusszone als der jeweilige Grundwerkstoff unabhaengig vom untersuchten Grundwerkstofftyp. Orientierende Schwingungskorrosionsversuche (Wechselbiegeversuche) an Luft und in kuenstlichem Meerwasser zeigten keine signifikanten Unterschiede zwischen den geprueften Werkstoffpaarungen. Die Naturversuche unter Freibewitterung auf Sylt und in Zinnwald erbrachten, dass die untersuchten Werkstoffe und ihre Schweissnaehte nach ca. einjaehriger Beanspruchung kaum korrosiv angegriffen wurden. (orig./MM)Available from TIB Hannover: F94B1210 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEArbeitsgemeinschaft Industrieller Forschungsvereinigungen e.V., Koeln (Germany)DEGerman

Einfluss von inneren und aeusseren Grenzflaechen auf den Wirkungsgrad von photovoltaischen Zellen auf Silizium-Basis Jahresbericht 1991 und 1. Zwischenbericht

Available from TIB Hannover: F95B191 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Einfluss von inneren und aeusseren Grenzflaechen auf den Wirkungsgrad von photovoltaischen Zellen auf Silizium-Basis Abschlussbericht

SIGLEAvailable from TIB Hannover: DtF QN1(25,23) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Mudança climática e adaptação no Brasil: uma análise crítica

Regiões semiáridas são consideradas altamente suscetíveis aos impactos adversos da mudança climática. Nesse contexto, o governo federal começou a implementar uma série de medidas para reduzir a vulnerabilidade de grupos menos preparados, como a agricultura familiar, para lidar com futuras mudanças. Baseado numa análise da legislação vigente sobre mudanças climáticas e dos principais documentos oficiais publicados, o presente trabalho identifica cinco fatores de preocupação referentes à atual abordagem que podem impedir uma redução sustentável de vulnerabilidade em áreas de risco no sertão brasileiro. Dado que grande parte da agricultura familiar já está fortemente impactada no contexto da variabilidade climática atual, isso implica que ações que reduzem a sua vulnerabilidade não dependem necessariamente da certeza de futuros impactos climáticos. Assim, medidas que tentam reduzir as existentes vulnerabilidades socioeconômicas e ambientais podem ser mais úteis para tornar a agricultura familiar do Nordeste mais resiliente às mudanças previstas