4,247 research outputs found
The potential impact of antifungal drug resistance mechanisms on the host immune response to Candida.
No full textA large number of studies have been published over the last two decades examining molecular mechanisms of antifungal resistance in Candida species. However, few of these studies have explored how such mechanisms influence the host immune response to this opportunistic pathogen. With recent advances in our understanding of host immunity to Candida, a body of emerging literature has begun to explore how intrinsic and adaptive resistance mechanisms in Candida alter host immune system evasion and detection, which could have important implications for understanding (1) why certain resistance mechanisms and Candida species predominate in certain patient populations, (2) the biological context for understanding why high in vitro levels of resistance in may not necessarily
correlate with risk of drug failure in vivo and (3) insight into effective immunotherapeutic strategies for combatting Candida resistance. Although this area of research is still in its infancy, two themes are emerging: First, the immunoevasion and intracellular persistence of C. glabrata may be a key factor in the capability of this species to persist in the course of multiple antifungal treatments and develop multidrug resistance. Second, changes in the cell wall associated with antifungal resistance often favor evasion for the host immune respons
Assessing the effectiveness of multi-touch interfaces for DP operation
No full textNavigating a vessel using dynamic positioning (DP) systems close to offshore installations is a challenge. The operator's only possibility of manipulating the system is through its interface, which can be categorized as the physical appearance of the equipment and the visualization of the system. Are there possibilities of interaction between the operator and the system that can reduce strain and cognitive load during DP operations? Can parts of the system (e.g. displays) be physically brought closer to the user to enhance the feeling of control when operating the system? Can these changes make DP operations more efficient and safe? These questions inspired this research project, which investigates the use of multi-touch and hand gestures known from consumer products to directly manipulate the visualization of a vessel in the 3D scene of a DP system. Usability methodologies and evaluation techniques that are widely used in consumer market research were used to investigate how these interaction techniques, which are new to the maritime domain, could make interaction with the DP system more efficient and transparent both during standard and safety-critical operations. After investigating which gestures felt natural to use by running user tests with a paper prototype, the gestures were implemented into a Rolls-Royce DP system and tested in a static environment. The results showed that the test participants performed significantly faster using direct gesture manipulation compared to using traditional button/menu interaction. To support the results from these tests, further tests were carried out. The purpose is to investigate how gestures are performed in a moving environment, using a motion platform to simulate rough sea conditions. The key results and lessons learned from a collection of four user experiments, together with a discussion of the choice of evaluation techniques will be discussed in this paper
A common HLA-DPA1 variant is associated with hepatitis B virus infection but fails to distinguish active from inactive Caucasian carriers
No full textBackground and Aims: Chronic infection with the hepatitis B virus (HBV) is a major health issue worldwide. Recently, single nucleotide polymorphisms (SNPs) within the human leukocyte antigen (HLA)-DP locus were identified to be associated with HBV infection in Asian populations. Most significant associations were observed for the A alleles of HLA-DPA1 rs3077 and HLA-DPB1 rs9277535, which conferred a decreased risk for HBV infection. We assessed the implications of these variants for HBV infection in Caucasians.
Methods: Two HLA-DP gene variants (rs3077 and rs9277535) were analyzed for associations with persistent HBV infection and with different clinical outcomes, i.e., inactive HBsAg carrier status versus progressive chronic HBV (CHB) infection in Caucasian patients (n = 201) and HBsAg negative controls (n = 235).
Results: The HLA-DPA1 rs3077 C allele was significantly associated with HBV infection (odds ratio, OR = 5.1, 95% confidence interval, CI: 1.9–13.7; p = 0.00093). However, no significant association was seen for rs3077 with progressive CHB infection versus inactive HBsAg carrier status (OR = 2.7, 95% CI: 0.6–11.1; p = 0.31). In contrast, HLA-DPB1 rs9277535 was not associated with HBV infection in Caucasians (OR = 0.8, 95% CI: 0.4–1.9; p = 1).
Conclusions: A highly significant association of HLA-DPA1 rs3077 with HBV infection was observed in Caucasians. However, as a differentiation between different clinical courses of HBV infection was not possible, knowledge of the HLA-DPA1 genotype cannot be translated into personalized anti-HBV therapy approaches
On the effects of non-linearities in DP systems
No full textIn offshore operations a trend is forming where vessels are more often required to do multiple short operations within a small-time frame. Traditional mooring systems require execution time far beyond the operation time. Dynamic positioning systems offer great advantages for short time span operations such as crew transfer or lift operations. Currently operations are planned based on DP capability plots and experience of captain and DPO. DP capability plots have little operational value as this is a static calculation and only provide information for average station keeping capability. During operations, the displacements made by the vessel around the DP set-point, also referred to as DP offset, are of great importance to determine the operability of an operation. Currently, the only way of calculating the DP offset is by conducting extensive time domain simulations, which are hard to integrate in the operational workflow of a DP vessel involved in walk-to-work operations. Therefore, a new approach is developed which predicts the vessel’s DP offset in the frequency domain, which enables a quick and robust calculation of the DP offset which is suited to merge into the on-board workflow. A frequency domain model is per definition a linear model. This leads to the main challenge of this research. A vessel operating on DP is non-linear. Currently there is no insight in what the effect is of non-linear components present in a DP system, on the linear approximation of a frequency domain model. To investigate the effect of non-linear components onto the DP frequency domain model, a time domain model is developed that is capable of systematically enabling/disabling different non-linear components. The time domain model will serve as the ’truth’ in this research as no actual vessel data is available. Furthermore, this helps identify the effects more easily, as the input for both models are identical. From the time domain model transfer functions can be derived that serve as the basis for the frequency domain model. The transfer function is a linear relation between two variables. In this case, between second order wave drift forces and displacement of the vessel in surge, sway and yaw direction. The following non-linear components are investigated in this research: Thruster ramp up, thruster turning rate, forbidden zones, saturation and thruster allocation. Thruster allocation is present in each model that will be tested, as this is an essential part of a DP system. Using two methods of determining transfer functions the model and the effects of all non-linear components are tested. The model is subjected to a variety sea-state, with different wave directions. Both methods offer similar results even though different approaches to determine the transfer functions are used. The selected method is capable of accurately predicting vessel offsets, although some extreme offsets are not captured. It is concluded that the presence of non-linear components have little to no effect on the DP offset as calculated by the time domain model. Because natural frequencies characteristic to these non-linear components are expected to exist at much higher frequencies that naturally present in second order wave drift forces. Thus, making a linear frequency domain model suitable for DP offset forecasting. It is advised to investigate the effect of including 2D input spectra as this is expected to improve the current model.<br/
Associative Plurality and the DP/NP typology
No full textThis paper investigates the phenomenon of additive plural morphology being used to denote the associative plural in a variety of languages. A novel empirical generalization is proposed: Languages with identical additive and associative plural morphology lack free standing definite articles. This follows a line of generalizations made by Boskovic (2008, 2012), who argues that languages without free standing definite articles do not project the DP layer, though the proposed generalization groups affixal article languages with languages without articles (see also Talic (2017)). I propose a new analysis of associative plurals that yields the empirical generalization for free. I argue that Num, the position of additive plural morphology, moves to Associative, which heads a projection on top of the nominal domain. This movement operation is blocked by the presence of D/DP in free standing definite article languages
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