586 research outputs found
Adaption of the ex vivo mycobacterial growth inhibition assay for use with murine lung cells.
In the absence of a correlate(s) of protection against human tuberculosis and a validated animal model of the disease, tools to facilitate vaccine development must be identified. We present an optimised ex vivo mycobacterial growth inhibition assay (MGIA) to assess the ability of host cells within the lung to inhibit mycobacterial growth, including Bacille Calmette-Guérin (BCG) and Mycobacterium tuberculosis (MTB) Erdman. Growth of BCG was reduced by 0.39, 0.96 and 0.73 log10 CFU following subcutaneous (s.c.) BCG, intranasal (i.n.) BCG, or BCG s.c. + mucosal boost, respectively, versus naïve mice. Comparatively, a 0.49 (s.c.), 0.60 (i.n.) and 0.81 (s.c. + mucosal boost) log10 reduction in MTB CFU was found. A BCG growth inhibitor, 2-thiophenecarboxylic acid hydrazide (TCH), was used to prevent quantification of residual BCG from i.n. immunisation and allow accurate MTB quantification. Using TCH, a further 0.58 log10 reduction in MTB CFU was revealed in the i.n. group. In combination with existing methods, the ex vivo lung MGIA may represent an important tool for analysis of vaccine efficacy and the immune mechanisms associated with vaccination in the organ primarily affected by MTB disease
Exploring the use of strategic frameworks in dental practice
This paper explores the use of strategic frameworks in NHS and private dental practice. It reviews the policy context of dentistry and suggests the challenges in this context will require dental practices to prioritise understanding and engagement with a strategic approach. A strategic approach will be required in order to enhance and improve performance. Two specific strategic frameworks will be explored in terms of their relevance to NHS and private dental practic
Intracellular replication of the well-armed pathogen Burkholderia pseudomallei.
The Burkholderia genus contains a group of soil-dwelling Gram-negative organisms that are prevalent in warm and humid climates. Two species in particular are able to cause disease in animals, B. mallei primarily infects Equus spp. and B. pseudomallei (BPS), that is able to cause potentially life-threatening disease in humans. BPS is naturally resistant to many antibiotics and there is no vaccine available. Although not a specialised human pathogen, BPS possesses a large genome and many virulence traits that allow it to adapt and survive very successfully in the human host. Key to this survival is the ability of BPS to replicate intracellularly. In this review we highlight recent advances in our understanding of the intracellular survival of BPS, including how it overcomes host immune defenses and other challenges to establish its niche and then spread the infection. Knowledge of these mechanisms increases our capacity for therapeutic interventions against a well-armed foe
Thermal refraction: implications for subglacial heat flux
First published online: 12 May 2021In this study, we explore small-scale (~1 to 20 km) thermal-refractive effects on basal geothermal heat flux (BGHF) at subglacial boundaries resulting from lateral thermal conductivity contrasts associated with subglacial topography and geologic contacts. We construct a series of two-dimensional, conductive, steady-state models that exclude many of the complexities of ice sheets in order to demonstrate the effect of thermal refraction. We show that heat can preferentially flow into or around a subglacial valley depending on the thermal conductivity contrast with underlying bedrock, with anomalies of local BGHF at the ice–bedrock interface between 80 and 120% of regional BGHF and temperature anomalies on the order of ±15% for the typical range of bedrock conductivities. In the absence of bed topography, subglacial contacts can produce significant heat flux and temperature anomalies that are locally extensive (>10 km). Thermal refraction can result in either an increase or decrease in the likelihood of melting and ice-sheet stability depending on the conductivity contrast and bed topography. While our models exclude many of the physical complexities of ice behavior, they illustrate the need to include refractive effects created by realistic geology into future glacial models to improve the prediction of subglacial melting and ice viscosity.Simon Willcocks, Derrick Hasterok, Samuel Jenning
A Method to Improve the Early Stages of the Robotic Process Automation Lifecycle
The robotic automation of processes is of much interest to
organizations. A common use case is to automate the repetitive manual
tasks (or processes) that are currently done by back-office staff
through some information system (IS). The lifecycle of any Robotic Process
Automation (RPA) project starts with the analysis of the process
to automate. This is a very time-consuming phase, which in practical
settings often relies on the study of process documentation. Such documentation
is typically incomplete or inaccurate, e.g., some documented
cases never occur, occurring cases are not documented, or documented
cases differ from reality. To deploy robots in a production environment
that are designed on such a shaky basis entails a high risk. This paper
describes and evaluates a new proposal for the early stages of an RPA
project: the analysis of a process and its subsequent design. The idea is to
leverage the knowledge of back-office staff, which starts by monitoring
them in a non-invasive manner. This is done through a screen-mousekey-
logger, i.e., a sequence of images, mouse actions, and key actions
are stored along with their timestamps. The log which is obtained in
this way is transformed into a UI log through image-analysis techniques
(e.g., fingerprinting or OCR) and then transformed into a process model
by the use of process discovery algorithms. We evaluated this method for
two real-life, industrial cases. The evaluation shows clear and substantial
benefits in terms of accuracy and speed. This paper presents the method,
along with a number of limitations that need to be addressed such that
it can be applied in wider contexts.Ministerio de EconomÃa y Competitividad TIN2016-76956-C3-2-
High-throughput analysis of Yersinia pseudotuberculosis gene essentiality in optimised in vitro conditions, and implications for the speciation of Yersinia pestis.
BACKGROUND: Yersinia pseudotuberculosis is a zoonotic pathogen, causing mild gastrointestinal infection in humans. From this comparatively benign pathogenic species emerged the highly virulent plague bacillus, Yersinia pestis, which has experienced significant genetic divergence in a relatively short time span. Much of our knowledge of Yersinia spp. evolution stems from genomic comparison and gene expression studies. Here we apply transposon-directed insertion site sequencing (TraDIS) to describe the essential gene set of Y. pseudotuberculosis IP32953 in optimised in vitro growth conditions, and contrast these with the published essential genes of Y. pestis. RESULTS: The essential genes of an organism are the core genetic elements required for basic survival processes in a given growth condition, and are therefore attractive targets for antimicrobials. One such gene we identified is yptb3665, which encodes a peptide deformylase, and here we report for the first time, the sensitivity of Y. pseudotuberculosis to actinonin, a deformylase inhibitor. Comparison of the essential genes of Y. pseudotuberculosis with those of Y. pestis revealed the genes whose importance are shared by both species, as well as genes that were differentially required for growth. In particular, we find that the two species uniquely rely upon different iron acquisition and respiratory metabolic pathways under similar in vitro conditions. CONCLUSIONS: The discovery of uniquely essential genes between the closely related Yersinia spp. represent some of the fundamental, species-defining points of divergence that arose during the evolution of Y. pestis from its ancestor. Furthermore, the shared essential genes represent ideal candidates for the development of novel antimicrobials against both species
Amperometric and spectrophotometric determination of carbaryl in natural waters and commercial formulations
The work presented describes the development
and evaluation of two flow-injection analysis (FIA) systems
for the automated determination of carbaryl in spiked
natural waters and commercial formulations. Samples are
injected directly into the system where they are subjected
to alkaline hydrolysis thus forming 1-naphthol. This product
is readily oxidised at a glassy carbon electrode. The
electrochemical behaviour of 1-naphthol allows the development
of an FIA system with an amperometric detector
in which 1-naphthol determination, and thus measurement
of carbaryl concentration, can be performed. Linear response
over the range 1.0×10–7 to 1.0×10–5 mol L–1, with a
sampling rate of 80 samples h–1, was recorded. The detection
limit was 1.0×10–8 mol L–1. Another FIA manifold was
constructed but this used a colorimetric detector. The methodology
was based on the coupling of 1-naphthol with phenylhydrazine
hydrochloride to produce a red complex which
has maximum absorbance at 495 nm. The response was
linear from 1.0×10–5 to 1.5×10–3 mol L–1 with a detection
limit of 1.0×10–6 mol L–1. Sample-throughput was about
60 samples h–1. Validation of the results provided by the
two FIA methodologies was performed by comparing
them with results from a standard HPLC–UV technique.
The relative deviation was <5%. Recovery trials were also
carried out and the values obtained ranged from 97.0 to
102.0% for both methods. The repeatability (RSD, %) of
12 consecutive injections of one sample was 0.8% and
1.6% for the amperometric and colorimetric systems, respectively
Towards an OpenSource Logger for the Analysis of RPA Projects
Process automation typically begins with the observation of
humans conducting the tasks that will be eventually automated. Sim ilarly, successful RPA projects require a prior analysis of the undergo ing processes which are being executed by humans. The process of col lecting this type of information is known as user interface (UI) logging
since it records the interaction against a UI. Main RPA platforms (e.g.,
Blueprism and UIPath) incorporate functionalities that allow the record ing of these UI interactions. However, the records that these platforms
generate lack some functionalities that large-scale RPA projects require.
Besides, they are only understandable by the proper RPA platforms.
This paper presents an extensible and multi-platform OpenSource UI
logger that generate UI logs in a standard format. This system collects
information from all the computers it is running on and sends it to a
central server for its processing. Treatment of the collected information
will allow the creation of an enriched UI log which can be used, among
others purposes, for smart process analysis, machine learning training,
the creation of RPA robots, or, being more general, for task mining .Ministerio de EconomÃa y Competitividad TIN2016-76956-C3-2-R (POLOLAS)Junta de AndalucÃa CEI-12-TIC021Centro para el Desarrollo Tecnol´ogico Industrial (CDTI) P011-19/E0
UK Housing Market: Time Series Processes with Independent and Identically Distributed Residuals
The paper examines whether a univariate data generating process can be identified which explains the data by having residuals that are independent and identically distributed, as verified by the BDS test. The stationary first differenced natural log quarterly house price index is regressed, initially with a constant variance and then with a conditional variance. The only regression function that produces independent and identically distributed standardised residuals is a mean process based on a pure random walk format with Exponential GARCH in mean for the conditional variance. There is an indication of an asymmetric volatility feedback effect but higher frequency data is required to confirm this. There could be scope for forecasting the index but this is tempered by the reduction in the power of the BDS test if there is a non-linear conditional variance process
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