3,219 research outputs found
Título: An exposition of the scientific, moral and commercial economy of the factory system of Great Britain
No full textSignaturizad
Efficient poultry housing, G. J. Simmonds; illustrated with plans, drawings and photographs by the author.
No full text25 p.
Structural constraints on RNA virus evolution
No full textThe recently discovered hepatitis G virus (HGV) or GB virus C (GBV-C) is widely distributed in human populations, and homologues such as HGV/GBV-CCPZ and GBV-A are found in a variety of different primate species. Both epidemiological and phylogenetic analyses support the hypothesis that GB viruses coevolved with their primate hosts, although their degree of sequence similarity appears incompatible with the high rate of sequence change of HGV/GBV-C over short observation periods. Comparison of complete coding sequences (8,500 bases) of different genotypes of HGV/GBV-C showed an excess of invariant synonymous sites (at 23% of all codons) compared with the frequency expected by chance (10%). To investigate the hypothesis that RNA secondary-structure formation through internal base pairing limited sequence variability at these sites, an algorithm was developed to detect covariant sites among HGV/GBV-C sequences of different genotypes. At least 35 covariant sites that were spatially associated with potential stem-loop structures were detected, whose positions correlated with positions in the genome that showed reductions in synonymous variability. Although the functional roles of the predicted secondary structures remain unclear, the restriction of sequence change imposed by secondary-structure formation provides a mechanism for differences in net rate of accumulation of nucleotide substitutions at different sites. However, the resulting disparity between short- and long-term rates of sequence change of HGV/GBV-C violates the assumptions of the "molecular clock." This places a major restriction on the use of nucleotide or amino acid sequence comparisons to calculate times of divergence of other viruses evolving under the same structural constraints as GB viruses
Detection of genome-scale ordered RNA structure (GORS) in genomes of positive-stranded RNA viruses:Implications for virus evolution and host persistence
No full textDiscrete RNA secondary and higher-order structures, typically local in extent, play a fundamental role in RNA virus replication. Using new bioinformatics analysis methods, we have identified genome-scale ordered RNA structure (GORS) in many genera and families of positive-strand animal and plant RNA viruses. There was remarkably variability between genera that possess this characteristic; for example, hepaciviruses in the family Flaviviridae show evidence for extensive internal base-pairing throughout their coding sequences that was absent in both the related pestivirus and flavivirus genera. Similar genus-associated variability was observed in the Picornaviridae, the Caliciviridae, and many plant virus families. The similarity in replication strategies between genera in each of these families rules out a role for GORS in a fundamentally conserved aspect of this aspect of the virus life cycle. However, in the Picornaviridae, Flaviviridae, and Caliciviridae, the existence of GORS correlated strongly with the ability of each genus to persist in their natural hosts. This raises the intriguing possibility of a role for GORS in the modulation of innate intracellular defense mechanisms (and secondarily, the acquired immune system) triggered by double-stranded RNA, analogous in function to the expression of structured RNA transcripts by large DNA viruses. Irrespective of function, the observed evolutionary conservation of GORS in many viruses imposes a considerable constraint on genome plasticity and the consequent narrowing of sequence space in which neutral drift can occur. These findings potentially reconcile the rapid evolution of RNA viruses over short periods with the documented examples of extreme conservatism evident from their intimate coevolution with their hosts
CLINICAL EVALUATION OF A SINGLE REACTION, DIAGNOSTIC PCR ASSAY FOR THE DETECTION OF HEPATITIS C VIRUS (HCV) RNA
No full textBACKGROUND/AIMS: In the past few years the detection of HCV-RNA by polymerase chain reaction has become a well-established diagnostic tool for patients with chronic hepatitis C. However, the lack of reproducible results between laboratories and the relatively high proportion of false-positive results, has indicated the need for a standardized and reliable polymerase chain reaction assay. In the present study we have analyzed the performance of a commercial, HCV-RNA polymerase chain reaction assay based on a single, combined reverse transcription and amplification reaction and on the use of Uracil-N-glycosilase to prevent carry-over contamination (Amplicor HCV, Roche Molecular Systems).
METHODS: In this assay the amplification products are detected in microwell plates using biotinylated primer and the HRP avidin colorimetric system. Serum samples collected from 446 patients, including 181 with chronic active hepatitis C, 50 with autoimmune chronic hepatitis, 117 in hemodialysis, 30 asymptomatic carriers of anti-HCV and 68 with indeterminate serology (RIBA indeterminate results), as well as from 121 controls were tested with the commercial, single-step assay and with nested polymerase chain reaction. Both techniques use primers located within the 5' non-coding region of the HCV genome.
RESULTS: In all cases a good concordance was observed between the commercial, single-step assay and nested polymerase chain reaction which, for patients with chronic active hepatitis, showed a sensitivity and specificity of 100% and 99.3% for the former and of 98.8% and 100% for the latter, when compared to clinical diagnosis taken as the gold standard. Most of the 11 discordant samples were seen in the group of RIBA-indeterminate cases and in patients with chronic active hepatitis C. Further analysis of these cases, based on repeat testing and clinical data showed that 64% and 36% of the discrepancies were due, respectively, to nested polymerase chain reaction and Amplicor inconsistent reactions. In hemodialyzed patients, patients with autoimmune hepatitis and asymptomatic carriers of anti-HCV, both assays produced results which were consistent with the clinical diagnosis. In the former group, polymerase chain reaction was able to identify the presence of active viral replication in some antibody negative samples.
CONCLUSIONS: Taken together, these results indicate that the commercial, single-step polymerase chain reaction assay has the same clinical sensitivity and specificity as nested polymerase chain reaction and that, because of its simplified procedures and fast turn-around time, it may be a valuable test for routine diagnostic applications
Improving patient experience of cancer follow up: redesign and evaluation of adult cancer aftercare services for breast, colorectal, and testicular patients, at University Hospital Southampton NHS Foundation Trust
No full textRandomized, double-blind, placebo-controlled, multicenter trial of 6% miltefosine solution, a topical chemotherapy in cutaneous metastases from breast cancer
No full textPurpose: to compare 6% miltefosine solution (Miltex; Asta Medica, Frankfurt, Germany), a new topical cytostatic drug, with placebo as palliative treatment for cutaneous metastases from breast cancer.Patients and methods: in a double-blind, placebo-controlled, multicenter phase III study, a total of 52 patients with inoperable progressive skin lesions from histologically or cytologically confirmed breast cancer, not manageable by radiotherapy or systemic treatment, with superficial or flat skin lesions (estimated depth of invasion <= 1 cm) were randomized to receive either 6% miltefosine solution or placebo. The solution was applied at the dose of 2 drops/10 cm2, once daily during the first week and twice daily thereafter until treatment failure.Results: treatment groups were well balanced for patient characteristics at study entry except for a small difference in age. Time to treatment failure (TTF), the primary parameter of this study, showed miltefosine solution to be significantly superior to placebo (P = .007); the median TTF in the miltefosine solution group was nearly three times longer than that in the placebo group (56 days v 21 days). The rate of response based on intention to treat patients was 33.3% for miltefosine solution compared with 3.7% for placebo (P = .006). Cutaneous reactions were seen mainly in the miltefosine group, with the type and frequency similar to those observed in previous studies.Conclusion: 6% Miltefosine solution is confirmed as an effective palliative treatment option for cutaneous metastases from breast cancer. Skin reactions, when present, are well tolerated and only occasionally require cessation of treatment.<br/
Obtención de ácido cítrico por fermentación con aspergillus niger utilizando sustrato de plátano dominico hartón (musa aab simmonds) maduro
No full textRipe Dominico Hartón plantain fruits (Musa AAB Simmonds) were used
in the elaboration of a liquid substratum from the pulp. Contents of Mn, Zn, Fe, Mg,
Cu, N and P in the substratum were determined, in order to evaluate if the concentration
of the metals was among the appropriate ranges for the metabolic processes of
Aspergillus niger, being discarded the addition or removal of some of these metals. In
this paper we present some results of a work performed in order to obtain citric acid
from substratum made with ripe Dominico Hartón pulp, using the stump of the Aspergillus
niger fungus (donated by EAFIT university). It was used an inoculate to 5%
of suspension of spores (approximate concentration of 1.0X107 spores/mL) for the
in-batch fermentation process. A volume of 2 liters of banana substratum was used,Los frutos de plátano Dominico Hartón (Musa AAB Simmonds) en estado
maduro se utilizaron en la elaboración de un sustrato líquido a partir de la pulpa. Al
sustrato se le determinó el contenido de Mn, Zn, Fe, Mg, Cu, N y P, para evaluar si la
concentración de los metales estaba dentro de los rangos permitidos para los procesos
metabólicos del Aspergillus niger, descartándose la adición o remoción de alguno de
éstos. En el trabajo del que da cuenta este artículo se obtuvo ácido cítrico a partir de
sustrato de pulpa de plátano Dominico Hartón en estado maduro, empleando la cepa
del hongo Aspergillus niger (donada por la universidad EAFIT). Se utilizó un inóculo
al 5% de suspensión de esporas (concentración aproximada de 1.0X107 esporas/mL)
para proceso de fermentación por lotes, se utilizó un volumen de 2 litros de sustrato
de plátano al cual se le ajustaron el pH y la concentración de azucares reductores,
para alcanzar el mejor rendimiento en la obtención de ácido. En la evaluación de la
efi ciencia de producción se obtuvieron 13.5 g/L de ácido cítrico
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