152 research outputs found
DNA immunization using a non-viral promoter
AbstractMost DNA vaccines rely on strong viral promoters to optimize levels of transgene expression. Some studies have demonstrated that the potency of viral promoters does not necessarily correlate with DNA vaccine efficacy in vivo. This has partly been attributed to downregulation of these promoters by cytokines such as interferon γ induced by the CpG motives of these vaccines. In an attempt to avoid downregulation of viral promoters by IFN-γ, we tested vaccine vectors driven by the MHC class II promoter. To enhance the activity of this promoter, another plasmid expressing the human MHC class II transactivator driven by a viral promoter, the native IFN-γ inducible CIITA type IV promoter (PIV) or a synthetic promoter containing IFN-γ inducible elements was co-inoculated. Our data show that a non-viral promoter such as the MHC class II promoter tested in this study can indeed be used in DNA vaccines
Rebirth of X-ray Emission from the Born-Again Planetary Nebula A 30
The planetary nebula (PN) A30 is believed to have undergone a very late
thermal pulse resulting in the ejection of knots of hydrogen-poor material.
Using HST images we have detected the angular expansion of these knots and
derived an age of 850+280-150 yr. To investigate the spectral and spatial
properties of the soft X-ray emission detected by ROSAT, we have obtained
Chandra and XMM-Newton observations of A30. The X-ray emission from A30 can be
separated into two components: a point-source at the central star and diffuse
emission associated with the hydrogen-poor knots and the cloverleaf structure
inside the nebular shell. To help us assess the role of the current stellar
wind in powering this X-ray emission, we have determined the stellar parameters
of the central star of A 30 using a non-LTE model fit to its optical and UV
spectrum. The spatial distribution and spectral properties of the diffuse X-ray
emission is suggestive that it is generated by the post-born-again and present
fast stellar winds interacting with the hydrogen-poor ejecta of the born-again
event. This emission can be attributed to shock-heated plasma, as the
hydrogen-poor knots are ablated by the stellar winds, under which circumstances
the efficient mass-loading of the present fast stellar wind raises its density
and damps its velocity to produce the observed diffuse soft X-rays. Charge
transfer reactions between the ions of the stellar winds and material of the
born-again ejecta has also been considered as a possible mechanism for the
production of diffuse X-ray emission, and upper limits on the expected X-ray
production by this mechanism have been derived. The origin of the X-ray
emission from the central star of A 30 is puzzling: shocks in the present fast
stellar wind and photospheric emission can be ruled out, while the development
of a new, compact hot bubble confining the fast stellar wind seems implausible.Comment: 29 pages, 11 figures, 4 tables; accepted for publication by Ap
A Survey of Cybersecurity of Digital Manufacturing
The Industry 4.0 concept promotes a digital manufacturing (DM) paradigm that can enhance quality and productivity, which reduces inventory and the lead time for delivering custom, batch-of-one products based on achieving convergence of additive, subtractive, and hybrid manufacturing machines, automation and robotic systems, sensors, computing, and communication networks, artificial intelligence, and big data. A DM system consists of embedded electronics, sensors, actuators, control software, and interconnectivity to enable the machines and the components within them to exchange data with other machines, components therein, the plant operators, the inventory managers, and customers. This article presents the cybersecurity risks in the emerging DM context, assesses the impact on manufacturing, and identifies approaches to secure DM
Personalized peptide-based vaccination for treatment of colorectal cancer: rational and progress
Colorectal cancer (CRC) is one of the most common cancers globally and is associated with a high rate of morbidity and mortality. A large proportion of patients with early stage CRC who undergo conventional treatments develop local recurrence or distant metastasis and in this group of advanced disease, the survival rate is low. Furthermore there is often a poor response and/or toxicity associated with chemotherapy and chemo-resistance may limit continuing conventional treatment alone. Choosing novel and targeted therapeutic approaches based on clinicopathological and molecular features of tumors in combination with conventional therapeutic approach could be used to eradicate residual micrometastasis and therefore improve patient prognosis and also be used preventively. Peptide-based vaccination therapy is one class of cancer treatment that could be used to induce tumor-specific immune responses, through the recognition of specific antigen-derived peptides in tumor cells, and this has emerged as a promising anti-cancer therapeutic strategy. The aim of this review was to summarize the main findings of recent studies in exciting field of peptide-based vaccination therapy in CRC patients as a novel therapeutic approach in treatment of CRC
Soluble forms of tau are toxic in Alzheimer's disease
Accumulation of neurofibrillary tangles (NFT), intracellular inclusions of fibrillar forms of tau, is a hallmark of Alzheimer Disease. NFT have been considered causative of neuronal death, however, recent evidence challenges this idea. Other species of tau, such as soluble misfolded, hyperphosphorylated, and mislocalized forms, are now being implicated as toxic. Here we review the data supporting soluble tau as toxic to neurons and synapses in the brain and the implications of these data for development of therapeutic strategies for Alzheimer’s disease and other tauopathies
The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set
Background
Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables.
Methods
Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set.
Results
Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001).
Conclusions
The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy
- …