1,507 research outputs found
Outcome measurement in clinical trials for Ulcerative Colitis: towards standardisation
Clinical trials on novel drug therapies require clear criteria for patient selection and agreed definitions of disease remission. This principle has been successfully applied in the field of rheumatology where agreed disease scoring systems have allowed multi-centre collaborations and facilitated audit across treatment centres. Unfortunately in ulcerative colitis this consensus is lacking. Thirteen scoring systems have been developed but none have been properly validated. Most trials choose different endpoints and activity indices, making comparison of results from different trials extremely difficult. International consensus on endoscopic, clinical and histological scoring systems is essential as these are the key components used to determine entry criteria and outcome measurements in clinical trials on ulcerative colitis. With multiple new therapies under development, there is a pressing need for consensus to be reached
Effects of a recombinant gene expression on ColE1-like plasmid segregation in Escherichia coli
<p>Abstract</p> <p>Background</p> <p>Segregation of expression plasmids leads to loss of recombinant DNA from transformed bacterial cells due to the irregular distribution of plasmids between the daughter cells during cell division. Under non-selective conditions this segregational instability results in a heterogeneous population of cells, where the non-productive plasmid-free cells overgrow the plasmid-bearing cells thus decreasing the yield of recombinant protein. Amongst the factors affecting segregational plasmid instability are: the plasmid design, plasmid copy-number, host cell genotype, fermentation conditions etc. This study aims to investigate the influence of transcription and translation on the segregation of recombinant plasmids designed for constitutive gene expression in <it>Escherichia coli </it>LE392 at glucose-limited continuous cultivation. To this end a series of pBR322-based plasmids carrying a synthetic human interferon-gamma (hIFNÎł) gene placed under the control of different regulatory elements (promoter and ribosome-binding sites) were used as a model.</p> <p>Results</p> <p>Bacterial growth and product formation kinetics of transformed <it>E. coli </it>LE392 cells cultivated continuously were described by a structured kinetic model proposed by Lee et al. (1985). The obtained results demonstrated that both transcription and translation efficiency strongly affected plasmid segregation. The segregation of plasmid having a deleted promoter did not exceed 5% after 190 h of cultivation. The observed high plasmid stability was not related with an increase in the plasmid copy-number. A reverse correlation between the yield of recombinant protein (as modulated by using different ribosome binding sites) and segregational plasmid stability (determined by the above model) was also observed.</p> <p>Conclusions</p> <p>Switching-off transcription of the hIFNÎł gene has a stabilising effect on ColE1-like plasmids against segregation, which is not associated with an increase in the plasmid copy-number. The increased constitutive gene expression has a negative effect on segregational plasmid stability. A kinetic model proposed by Lee et al. (1985) was appropriate for description of <it>E. coli </it>cell growth and recombinant product formation in chemostat cultivations.</p
pp32 (ANP32A) Expression Inhibits Pancreatic Cancer Cell Growth and Induces Gemcitabine Resistance by Disrupting HuR Binding to mRNAs
The expression of protein phosphatase 32 (PP32, ANP32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, including gemcitabine. pp32 overexpression reduced the association of HuR with the mRNA encoding the gemcitabine-metabolizing enzyme deoxycytidine kinase (dCK), causing a significant reduction in dCK protein levels. Similarly, ectopic pp32 expression caused a reduction in HuR binding of mRNAs encoding tumor-promoting proteins (e.g., VEGF and HuR), while silencing pp32 dramatically enhanced the binding of these mRNA targets. Low pp32 nuclear expression correlated with high-grade tumors and the presence of lymph node metastasis, as compared to patients' tumors with high nuclear pp32 expression. Although pp32 expression levels did not enhance the predictive power of cytoplasmic HuR status, nuclear pp32 levels and cytoplasmic HuR levels associated significantly in patient samples. Thus, we provide novel evidence that the tumor suppressor function of pp32 can be attributed to its ability to disrupt HuR binding to target mRNAs encoding key proteins for cancer cell survival and drug efficacy
An operational approach to high resolution agro-ecological zoning in West-Africa
Research ArticleThe objective of this work is to develop a simple methodology for high resolution crop suitability
analysis under current and future climate, easily applicable and useful in Least
Developed Countries. The approach addresses both regional planning in the context of
climate change projections and pre-emptive short-term rural extension interventions
based on same-year agricultural season forecasts, while implemented with off-the-shelf
resources. The developed tools are applied operationally in a case-study developed in
three regions of Guinea-Bissau and the obtained results, as well as the advantages
and limitations of methods applied, are discussed. In this paper we show how a simple
approach can easily generate information on climate vulnerability and how it can be operationally
used in rural extension servicesinfo:eu-repo/semantics/publishedVersio
Hormone Treatment without Surgery for Patients Aged 75 Years or Older with Operable Breast Cancer
Purpose. To evaluate the trend in the use of primary endocrine treatment (PET) for elderly patients with operable breast cancer and to study mean time to response (TTR), local control, time to progression (TTP), and overall survival.Methods. Data of 184 patients aged >= 75 years, diagnosed with breast cancer in the south of the Netherlands between 2001 and 2008 and receiving PET, were analyzed.Results. The percentage of women >= 75 years with breast cancer receiving PET in the south of the Netherlands decreased from 23% in the period 1988-1992 to 12% in 1997-2000, and increased to 29% in 2005-2008. Mean age at diagnosis of 184 patients treated with PET in the period 2001-2008 was 84 years (range 75-89 years). Mean length of follow-up was 2.6 years. In 107 patients (58%), an initial response was achieved (mean TTR 7 months), 21 patients (12%) showed stable disease. A total of 64 patients (35%), with or without prior response, eventually displayed progression (mean TTP 20 months). No differences in TTR and TTP were observed between the patients starting with tamoxifen or an aromatase inhibitor. One hundred nineteen (65%) of 184 patients had died by January 1, 2010. In 17 patients (14%), breast cancer was the cause of death.Conclusions. Tumor progression was observed in a substantial proportion of the cohort, but only a small number of patients died of breast cancer. Further research is needed on the safety and effectiveness of PET for elderly women with breast cancer to justify the current widespread use.Biological, physical and clinical aspects of cancer treatment with ionising radiatio
The Hubbard model within the equations of motion approach
The Hubbard model has a special role in Condensed Matter Theory as it is
considered as the simplest Hamiltonian model one can write in order to describe
anomalous physical properties of some class of real materials. Unfortunately,
this model is not exactly solved except for some limits and therefore one
should resort to analytical methods, like the Equations of Motion Approach, or
to numerical techniques in order to attain a description of its relevant
features in the whole range of physical parameters (interaction, filling and
temperature). In this manuscript, the Composite Operator Method, which exploits
the above mentioned analytical technique, is presented and systematically
applied in order to get information about the behavior of all relevant
properties of the model (local, thermodynamic, single- and two- particle ones)
in comparison with many other analytical techniques, the above cited known
limits and numerical simulations. Within this approach, the Hubbard model is
shown to be also capable to describe some anomalous behaviors of the cuprate
superconductors.Comment: 232 pages, more than 300 figures, more than 500 reference
Potential new genes for resistance to Mycosphaerella graminicola identified in Triticum aestivum x Lophopyrum elongatum disomic substitution lines.
Lophopyrum species carry many desirable agronomic traits, including disease resistance, which can be transferred towheat by interspecific hybridization. To identify potentially new genes for disease and insect resistance carried by individual Lophopyrum chromosomes, 19 of 21 possible wheat cultivar Chinese Spring 9 Lophopyrum elongatum disomic substitution lines were tested for resistance to barley yellow dwarf virus (BYDV), cereal yellow dwarf virus (CYDV), the Hessian fly Mayetiola destructor, and the fungal pathogens Blumeria graminis and Mycosphaerella graminicola (asexual stage: Septoria tritici). Low resistance to BYDV occurred in some of the disomic substitution lines, but viral titers were significantly higher than those of two Lophopyrum species tested. This suggested that genes on more than one Lophopyrum chromosome are required for complete resistance to this virus. A potentially new gene for resistance to CYDV was detected on wheatgrass chromosome 3E. All of the
substitution lines were susceptible to Mayetiola destructor
and one strain of B. graminis. Disomic substitution lines containing wheatgrass chromosomes 1E and 6E were significantly more resistant to M. graminicola compared to Chinese Spring. Although neither chromosome by itself conferred resistance as high as that in the wheatgrass parent, they do appear to contain potentially new genes for resistance against this pathogen that could be useful for future plant-improvement programs
Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set
We report a measurement of the bottom-strange meson mixing phase \beta_s
using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays
in which the quark-flavor content of the bottom-strange meson is identified at
production. This measurement uses the full data set of proton-antiproton
collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment
at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity.
We report confidence regions in the two-dimensional space of \beta_s and the
B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2,
-1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in
agreement with the standard model expectation. Assuming the standard model
value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +-
0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +-
0.009 (syst) ps, which are consistent and competitive with determinations by
other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
- âŚ