713 research outputs found
Maximizing mRNA vaccine production with Bayesian optimization
Messenger RNA (mRNA) vaccines are a new alternative to conventional vaccines with a prominent role in infectious disease control. These vaccines are produced in in vitro transcription (IVT) reactions, catalyzed by RNA polymerase in cascade reactions. To ensure an efficient and cost-effective manufacturing process, essential for a large-scale production and effective vaccine supply chain, the IVT reaction needs to be optimized. IVT is a complex reaction that contains a large number of variables that can affect its outcome. Traditional optimization methods rely on classic Design of Experiments methods, which are time-consuming and can present human bias or based on simplified assumptions. In this contribution, we propose the use of Machine Learning approaches to perform a data-driven optimization of an mRNA IVT reaction. A Bayesian optimization method and model interpretability techniques were used to automate experiment design, providing a feedback loop. IVT reaction conditions were found under 60 optimization runs that produced 12âgâ·âLâ1 in solely 2âh. The results obtained outperform published industry standards and data reported in literature in terms of both achievable reaction yield and reduction of production time. Furthermore, this shows the potential of Bayesian optimization as a cost-effective optimization tool within (bio)chemical applications
Vibrational analysis of d-PCL(530)/siloxane based hybrids doped with two lithium salts
Published online: 22 May 2013The present study has been focused on environmentally friendly sol-gel derived electrolytes based on a di-urethane cross-linked d-PCL(530)/siloxane network (where d represents di, PCL identifies the poly(Δâcaprolactone) biopolymer and 530 is the average molecular weight in g.mol-1) doped with a wide range of concentration of lithium perchlorate (LiClO4) and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI). Fourier Transform Infrared and Raman (FT-IR and FT-Raman, respectively) spectroscopies have been applied to evaluate the extent of ionic association. Characteristic bands of the PCL(530) segments, of the urethane cross-links and of the anions have been examined to gain insight into the cation/biopolymer, cation/anion and cation/cross-link interactions. In both electrolyte systems âfreeâ ions and contact ions have been identified. The addition of salt modifies the hydrogen-bonded array of the host matrix, causing the destruction/formation of the urethane/urethane aggregates.Fundação para a CiĂȘncia e a Tecnologia (FCT
Experimental model for learning in vascular surgery and microsurgery: esophagus and trachea of chicken
A large outbreak of Legionnairesâ Disease in an industrial town in Portugal
Background
We describe the investigation and control of an outbreak of Legionnairesâ disease in Portugal in October, November and December 2014.
Methods
Confirmed cases were individuals with pneumonia, laboratory evidence of Legionella pneumophila serogroup 1 and exposure, by residence, occupational or leisure to the affected municipalities. 49 possible sources were reduced to four potential sources, all industries with wet cooling system, following risk assessment. We geo-referenced casesâ residences and the location of cooling towers defining four study areas 10 km buffer centered on each cooling tower system. We compared the number of cases with expected numbers, calculated from the outbreak's attack rates applied to 2011 census population. Using Stonesâ Test, we tested observed to expected ratios for decline in risk, with distance up to 10 km four directions. Isolates of Legionella pneumophila were compared using molecular methods.
Results
We identified 403 cases, 377 of which were confirmed, 14 patients died. Patients became ill between 14 October and 2 December. A NE wind and thermal inversion were recorded during the estimated period of exposure. Disease risk was highest in people living south west from all of the industries identified and decreased with distance (p < 0.001). 71 clinical isolates demonstrated an identical SBT profile to an isolate from a cooling tower. Whole genome sequencing identified an unusual L. pneumophila subsp. fraseri serogroup 1 as the outbreak causative strain, and confirmed isolatesâ relatedness.
Conclusions
Industrial wet cooling systems, bacteria with enhanced survival characteristics and a combination of climatic conditions contributed to the second largest outbreak of Legionnairesâ disease recorded internationally.info:eu-repo/semantics/publishedVersio
A trajetĂłria das ciĂȘncias sociais em saĂșde na AmĂ©rica Latina: revisĂŁo da produção cientĂfica
Serum HER2 Level Measured by Dot Blot: A Valid and Inexpensive Assay for Monitoring Breast Cancer Progression
Human epidermal growth factor receptor 2 (HER2) is one of the most important
prognostic and predictive factors for breast cancer patients. Recently, serum
HER2 ECD level of patients detected by enzyme-linked immunoabsorbent assay
(ELISA) has been shown to predict tumor HER2 status and reveal its association
with tumor progression, recurrence and poor prognosis. In this study, we
established a new method, dot blot assay, to measure the serum HER2 level in
breast cancer patients and further to evaluate the clinical value for monitoring
breast cancer progression. We found that the serum HER2 level measured by dot
blot assay was significantly correlated with tissue HER2 status in breast cancer
patients (Pâ=â0.001), and also
significantly correlated with HER2 level measured by ELISA
(Pâ=â1.06Ă10â11).
Compared with ELISA method, the specificity and sensitivity of dot blot assay
were 95.3% and 65.0%, respectively. The serum HER2 levels of
patients with grade III or ER-negative were higher than those with grade
IâII (Pâ=â0.004) and ER-positive
(Pâ=â0.033), respectively. Therefore,
the novel dot blot method to detect serum HER2 level is a valid and inexpensive
assay with potential application in monitoring breast cancer progression in
clinical situations
The Warden Attitude: An investigation of the value of interaction with everyday wildlife
Using a discrete choice experiment, we elicit valuations of engagement with âeveryday wildlifeâ through feeding garden birds. We find that bird-feeding is primarily but not exclusively motivated by the direct consumption value of interaction with wildlife. The implicit valuations given to different species suggest that people prefer birds that have aesthetic appeal and that evoke human feelings of protectiveness. These findings suggest that people derive wellbeing by adopting a warden-like role towards âtheirâ wildlife. We test for external validity by conducting a hedonic analysis of sales of bird food. We discuss some policy implications of the existence of warden attitudes
Observation of associated near-side and away-side long-range correlations in âsNN=5.02ââTeV proton-lead collisions with the ATLAS detector
Two-particle correlations in relative azimuthal angle (ÎÏ) and pseudorapidity (Îη) are measured in âsNN=5.02ââTeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1ââÎŒb-1 of data as a function of transverse momentum (pT) and the transverse energy (ÎŁETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Îη|<5) ânear-sideâ (ÎÏâŒ0) correlation that grows rapidly with increasing ÎŁETPb. A long-range âaway-sideâ (ÎÏâŒÏ) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ÎŁETPb, is found to match the near-side correlation in magnitude, shape (in Îη and ÎÏ) and ÎŁETPb dependence. The resultant ÎÏ correlation is approximately symmetric about Ï/2, and is consistent with a dominant cosâĄ2ÎÏ modulation for all ÎŁETPb ranges and particle pT
O modelo de atenção a saĂșde bucal no MĂ©dio e Baixo Xingu: parcerias, processos e perspectivas
Carbohydrate hydrogels with stabilized phage particles for bacterial biosensing: bacterium diffusion studies
Bacteriophage particles have been reported as potentially useful in the development of diagnosis tools for pathogenic bacteria as they specifically recognize and lyse bacterial isolates thus confirming the presence of viable cells. One of the most representative microorganisms associated with health care services is the bacterium Pseudomonas aeruginosa, which alone is responsible for nearly 15 % of all nosocomial infections. In this context, structural and functional stabilization of phage particles within biopolymeric hydrogels, aiming at producing cheap (chromogenic) bacterial biosensing devices, has been the goal of a previous research effort. For this, a detailed knowledge of the bacterial diffusion profile into the hydrogel core, where the phage particles lie, is of utmost importance. In the present research effort, the bacterial diffusion process into the biopolymeric hydrogel core was mathematically described and the theoretical simulations duly compared with experimental results, allowing determination of the effective diffusion coefficients of P. aeruginosa in the agar and calcium alginate hydrogels tested.Financial support to Victor M. Balcao, via an Invited Research Scientist fellowship (FAPESP Ref. No. 2011/51077-8) by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Sao Paulo, Brazil), is hereby gratefully acknowledged
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