9,916 research outputs found
The CTLA-4 and PD-1/PD-L1 inhibitory pathways independently regulate host resistance to Plasmodium-induced acute immune pathology.
No full textThe balance between pro-inflammatory and regulatory immune responses in determining optimal T cell activation is vital for the successful resolution of microbial infections. This balance is maintained in part by the negative regulators of T cell activation, CTLA-4 and PD-1/PD-L, which dampen effector responses during chronic infections. However, their role in acute infections, such as malaria, remains less clear. In this study, we determined the contribution of CTLA-4 and PD-1/PD-L to the regulation of T cell responses during Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM) in susceptible (C57BL/6) and resistant (BALB/c) mice. We found that the expression of CTLA-4 and PD-1 on T cells correlates with the extent of pro-inflammatory responses induced during PbA infection, being higher in C57BL/6 than in BALB/c mice. Thus, ECM develops despite high levels of expression of these inhibitory receptors. However, antibody-mediated blockade of either the CTLA-4 or PD-1/PD-L1, but not the PD-1/PD-L2, pathways during PbA-infection in ECM-resistant BALB/c mice resulted in higher levels of T cell activation, enhanced IFN-γ production, increased intravascular arrest of both parasitised erythrocytes and CD8(+) T cells to the brain, and augmented incidence of ECM. Thus, in ECM-resistant BALB/c mice, CTLA-4 and PD-1/PD-L1 represent essential, independent and non-redundant pathways for maintaining T cell homeostasis during a virulent malaria infection. Moreover, neutralisation of IFN-γ or depletion of CD8(+) T cells during PbA infection was shown to reverse the pathologic effects of regulatory pathway blockade, highlighting that the aetiology of ECM in the BALB/c mice is similar to that in C57BL/6 mice. In summary, our results underscore the differential and complex regulation that governs immune responses to malaria parasites
DNA-Walker-Induced Allosteric Switch for Tandem Signal Amplification with Palladium Nanoparticles/Metal–Organic Framework Tags in Electrochemical Biosensing
No full textA DNA walker as a new molecular machine
can walk on defined tracks
to directly generate signal indicators in biosensing and biomedical
applications. In this work, a tandem signal amplification strategy
was developed on the basis of the DNA-walker-induced conformation
switch for bridging palladium nanoparticles/metal–organic framework
tags in ultrasensitive electrochemical DNA biosensing. The signal
tags were synthesized by in situ reduction of Pd nanocrystals on porphyrinic
metal–organic frameworks (PCN-224), followed by conjugation
with streptavidin (SA). The as-prepared Pd/PCN-224-SA tag could electrocatalyze
the oxidation of NaBH4 with high efficiency for signal
readout. The presence of target DNA released swing arms that were
each silenced by a blocker, and then the activated swing arms could
hybridize with hairpin DNA. The movement of swing arms was powered
by enzymatic cleavage of conjugated oligonucleotides, inducing the
allosteric switch from hairpin to SA aptamer. Therefore, Pd/PCN-224-SA
tags were brought onto the electrode surface via SA-aptamer biorecognition
to generate the enhanced electrochemical signal. The DNA walker-based
electrochemical biosensor demonstrated good performance such as 6
orders of magnitude linear range, femtomolar detection limit, and
single mismatch differentiation ability. Moreover, the feasibility
of the biosensor was identified in serum matrixes. The tandem signal
amplification of metal–organic frameworks and DNA walkers provided
a new avenue in trace electrochemical biosensing
A novel calibration method for PD measurement in power cables and joints using capacitive couplers
No full textPartial discharge (PD) measurements are universally accepted as a technique giving some indication of the state of the insulation in high voltage apparatus. Cable end users are keen to adopt an on-line PD monitoring during commissioning of systems. However, because of noisy environments and the problems of interference the conventional methods are difficult to implement. As a consequence, ultra-high frequency (UHF) / very high frequency (VHF) techniques of on-site detection of partial discharges have been developed. A technique based on the capacitive coupling has received much attention. It has been demonstrated that it is possible to using the technique to monitor the partial discharge in cables, particularly in joints/terminations. However, in order to obtain quantitative information about PD, calibration is required for this technique. Existing calibration methods are difficulty to implement on-site. In this paper a novel method is proposed and compared with the conventional method on a short piece of cable. It has been shown that individual capacitive coupler can also be accurately calibrated on-site and online using the new method, therefore it provides quantitative information about the amount of apparent discharge. In practice this is important for electricity utilities as the quantitative information about PD can be used to determine the quality of cable system and to decide whether the system needs to be repaired or replaced
A preliminary strategy for fall prevention in the ASBGo smart walker
No full textFall-related injuries affect a large part of the population and related costs. Thus, there is a concern in studying a fall prevention strategy to minimize the consequences of falls. Walkers are assistive devices used to improve the balance, stability and reduce the load on the lower limb of the user. In this sense, there is a concern to improve the safety in smart walkers and, consequently, to prevent falls in these devices. However, in this field, the only approach is to stop the walker in risk situations. So, the aim of this paper is to define a preliminary strategy to prevent a fall event in the Adaptive System Behaviour Group (ASBGo) Smart Walker. For ASBGo Smart Walker, two modes of security are discussed in this paper. One approach is based on monitoring the center of mass and changing the trajectory when a near fall is detected. The other mechanism consists only in to stop the walker when a dangerous situation is detected. The first or the second mode are activated depending if the user drives the walker with the forearm on forearm support or not.This work has been supported by the FCT – Fundação para a Ciência e Tecnologia - with the scholarship reference PD/BD/141515/2018, by the FEDER funds through the COMPETE 2020 - Programa Operacional Competitividade e Internacionalização (POCI) and P2020 with the Reference Project EML under Grant POCI-01-0247-FEDER-033067, and through the COMPETE 2020 - POCI - with the Reference Project under Grant POCI-01-0145-FEDER-00694
Implications of the Improvement of Teaching Quality for Professional Development (PD) of Academics at the Colleges of Applied Sciences (CASs) in the Sultanate of Oman
No full textThe Oman Accreditation Council (OAC), which is called later the Oman Academic Accreditation Authority (OAAA), designed a higher education institution (HEI) Quality Assurance (QA) framework for Omani public and private Higher Education Institutions (HEIs), starting with a quality audit process in 2008. The Colleges of Applied Sciences (CASs), as a public HEI, are required to ensure the quality of all services and activities to meet particular national standards (specified in the framework) in order to gain a HEI and programme certificate. In line with a quality audit scope, the quality of the fields of PD and related teaching quality should be ensured and enhanced by the promotion and contribution of the former field to the maintenance and improvement of the latter one.
The chief purpose of this study was to identify the uptake and implications of the growing requirement to improve teaching quality and the PD of academics at the CASs in the Sultanate of Oman especially in the context of the application of the QA framework. The study focused on examining the academics’ participation in professional development programmes (PDPs) and current perceptions of PD with respect to the improvement of teaching quality improvement at these colleges. The current study also dealt with a reorganization and prioritization of academics’ PD needs, barriers to effective PD, and factors to enhance PD of academics regarding teaching quality improvement in the colleges.
Based on the purpose and research objectives, the current study adopted both positivist (quantitative) and interpretive (qualitative) research paradigms. Because the study perused quantitative and qualitative data regarding certain variables, it chose a mixed-research design. The researcher designed survey questionnaire to collect quantitative data and a semi-structured interview and a focus group discussion to probe and interpret quantitative findings. After fulfillment of the validity and reliability measurements, a self-completion questionnaire was distributed to a stratified random sample of academics (170) over the six CASs. A total of 150 questionnaires (out of 170) were completed and returned and the response-rate reached 88.2%. The quantitative data was analyzed by appropriate analysis using the Statistical Package for Social sciences (SPSS), while the qualitative data was analyzed by appropriate qualitative analysis.
The findings of the study showed that the level of academics’ participation in PDPs to improve teaching quality in the last two years in the CASs seems to be unsatisfactorily low. The current perceptions of the PD situations in the colleges, relating to teaching quality improvement, signified a shortage in the number of available PDPs and/or a discouragement of academics’ participation in these programmes in the last two years. The study also revealed all the 22 PD needs of academics regarding the improvement of teaching quality are significantly demanded by participants; the higher rated needs focused on a development of ‘student centred’ skills, such as critical thinking and problem-solving skills.
Furthermore, the study illustrated that the highest significant perceived barriers to effective PD in the CASs, as related to teaching quality improvement, focus on a lack of a clear institutional PD policy and a lack of appropriately systematic PD plans. The study also revealed all 10 perceived factors to enhance PD regarding teaching quality improvement are very important. The most significant factors represented and stressed particular problematic issues (the high rated barriers) and a reduction of a heavy workload to enhance academics’ participation in PD regarding the improvement of teaching quality.
Conclusions drawn from the discussion of the findings of study include a lack of a clear PD policy at national and institutional levels and absence of a particular authority/unit concerning PD issues in Omani HEIs. The two problematic issues resulted in a lack of systematic and realistic PD plans in the CASs, involving a lack of academics’ involvement in PD plans, a misconnection of academics’ PD needs to PD, inappropriate facilities and resources allocation, and inappropriate evaluation processes of PD. In addition, the conclusions also include that PD of academics regarding the improvement of teaching quality in the colleges requires more attention and focus to manage particular significant issues perceived by participants as both barriers and potential facilitators relating to PD of academics.
Based on identified conclusions, particular implications for policy and practice to enhance PD to improve teaching quality were set at three levels: governmental, institutional, and individual. Moreover, achievements of the current study according to the research questions were identified and contributions of the study to the fields of PD, teaching quality, and the context of QA and quality audit in HE were addressed. Based on the findings and conclusions, particular directions and recommended issues were suggested to be studied by further research to benefit the enhancement of PD and related teaching quality improvement
A Smart Robotics Walker System for Heart Rate Monitoring and Walking Rehabilitation of PD
No full textParkinson’s disease (PD) typically causes motor and non-motor symptoms (NMS), where Freezing of Gait (FOG) is motor symptoms and Autonomic Nervous System (ANS), including changes in Heart Rate (HR), consider as non-motor manifestations. Most existing walker systems widely focus on FOG analysis without giving much attention to health monitoring feedback during rehabilitation. This study presents a smart robotics walker system (SRW) for HR monitoring and walking rehabilitation. The system framework interacts with a voice-based virtual assistant and simultaneous use of a PPG sensor. The proposed system framework provides an IoT platform by synchronizing real-time heart rates and rehabilitation information of the user. Meantime, PPG data interjects with the efforts of HEBI actuators to stop driving. The system performance presented a strategic analysis of HR changes with a non-PD person and PD patient by 10m steady line of walking. The result showed that HR rapidly increases while performing with PD patients than a non-PD subject, which validates the performance of walking rehabilitation. In addition, the user can know their HR condition in normal and abnormal situations, and the therapist can evaluate the success of the rehabilitation information from the IoT environment. We aim to provide a better rehabilitation IoT platform with SRW considering health conditions like the HR patterns of the user. The system can implement with any existing walker for PD patients.journal articl
Estimation of trace element concentrations in the lunar magma ocean using mineral- and metal-silicate melt partition coefficients
No full textAbstract–This study uses experimentally determined plagioclase-melt D values to estimate the trace element concentrations of Sr, Hf, Ga, W, Mo, Ru, Pd, Au, Ni, and Co in a crystallizing lunar magma ocean at the point of plagioclase flotation. Similarly, experimentally determined metal-silicate partition experiments combined with a composition model for the Moon are used to constrain the concentrations of W, Mo, Ru, Pd, Au, Ni, and Co in the lunar magma ocean at the time of core formation. The metal-silicate derived lunar mantle estimates are generally consistent with previous estimates for the concentration of these elements in the lunar mantle. Plagioclase-melt derived concentrations for Sr, Ga, Ru, Pd, Au, Ni, and Co are also consistent with prior estimates. Estimates for Hf, W, and Mo, however, are higher. These elements may be concentrated in the residual liquid during fractional crystallization due to their incompatibility. Alternatively, the apparent enrichment could reflect the inappropriate use of bulk anorthosite data, rather than data for plagioclase separates.This research was partially supported by NASA NLSI grant NNA09DB33A (to R. J. Walker), and RTOPs from the NASA LASER and NLSI programs (to K. Righter). M. Sharp was supported by the NASA Harriett G. Jenkins Pre-doctoral Fellowship NNX10AU20A
Identification, binding, and structural characterization of single domain anti-PD-L1 antibodies inhibitory of immune regulatory proteins PD-1 and CD80
No full textProgrammed death-ligand 1 (PD-L1) is a key immune regulatory protein that interacts with programmed cell death protein 1 (PD-1), leading to T-cell suppression. Whilst this interaction is key in self-tolerance, cancer cells evade the immune system by overexpressing PD-L1. Inhibition of the PD-1/PD-L1 pathway with standard monoclonal antibodies has proven a highly effective cancer treatment; however, single domain antibodies (VHH) may offer numerous potential benefits. Here, we report the identification and characterization of a diverse panel of 16 novel VHHs specific to PD-L1. The panel of VHHs demonstrate affinities of 0.7 nM to 5.1 μM and were able to completely inhibit PD-1 binding to PD-L1. The binding site for each VHH on PD-L1 was determined using NMR chemical shift perturbation mapping and revealed a common binding surface encompassing the PD-1–binding site. Additionally, we solved crystal structures of two representative VHHs in complex with PD-L1, which revealed unique binding modes. Similar NMR experiments were used to identify the binding site of CD80 on PD-L1, which is another immune response regulatory element and interacts with PD-L1 localized on the same cell surface. CD80 and PD-1 were revealed to share a highly overlapping binding site on PD-L1, with the panel of VHHs identified expected to inhibit CD80 binding. Comparison of the CD80 and PD-1 binding sites on PD-L1 enabled the identification of a potential antibody binding region able to confer specificity for the inhibition of PD-1 binding only, which may offer therapeutic benefits to counteract cancer cell evasion of the immune system
Fullerene-like WS<sub>2</sub> supported Pd catalyst for hydrogen evolution reaction
No full textHydrogen is the most desirable green energy carrier and electrocatalytic hydrogen evolution reaction (HER) from water is a promising route for hydrogen production. The search for efficient, low-cost HER catalysts is a challenging and attracting topic. In this work, we report that inorganic fullerene-like WS2 supported Pd nanoparticles (Pd/WS2), with Pd loading of 0.76 wt%, are active for electrocatalytic HER conducted in 0.5 M H2SO4 solution, with overpotential at 10 mA cm−2 current density of ~130 mV and Tafel slope of 82.4 mV dec−1, which is comparable to that of Pt/WS2 (0.88 wt% Pt loading) with higher costs. Characteristic results indicate that WO3 impurities were in-situ produced on the WS2 surface and the Pd NPs are primarily located inside the WS2 nanocages. Contrasting experiments suggest that the WO3 impurities play a crucial role in generating Hads intermediate and the Pd NPs are active sites of H2 production, and a reaction mechanism is proposed. The Pd/WS2 catalyst also shows good long-term stability owing to the location of Pd NPs inside the WS2 cages. The high HER activity, low costs and good stability make the Pd catalyst a potential alternative to Pt catalyst for HER.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Micro and Nano Engineerin
- …
