12508 research outputs found
Sort by
Genetically engineered multicistronic allele of Pmel yielding highly specific CreERT2-mediated recombination in the melanocyte lineage
Get PDFYesGenetic approaches that allow lineage tracing are essential to our future understanding of melanocytes and melanoma. To date, the approaches used to label melanocytes in mice have relied on random integration of transgenes driven by the promoters of the Tyrosinase and Dopachrome tautomerase genes, knock-in to the Dopachrome tautomerase locus or knock-in to the Mlana locus in a bacterial artificial chromosome. These strategies result in expression in other tissues such as telencephalon and other cell types such as nerves. Here we used homologous recombination in mouse embryonic stem cells to generate a targeted multicistronic allele of the Pmel locus that drives melanocyte-specific expression of CreERT2, nuclear localised H2B-Cerulean and membrane localised marcks-mKate2 allowing live imaging of melanocytes and activation of other conditional alleles. We combined this allele with R26R-EYFP mice allowing induction of EYFP expression on administration of tamoxifen or its metabolite 4-OHT. The fluorescent proteins H2B-Cerulean and marcks-mKate2 label the cell nucleus and plasma membrane respectively allowing live imaging and FACS isolation of melanoblasts and melanocytes as well as serving to provide an internal control allowing estimation of recombination efficiency after administration of tamoxifen. We demonstrate the utility of the transgene in embryonic and adult tissues.Cancer Research UK. Grant Number: A15673. Medical Research Council. Grant Number: MC_PC_U127527200. National Centre for the Replacement Refinement and Reduction of Animals in Research. Grant Number: NC/K001612/1. North West Cancer Research Fund. Grant Number: CR1132. Medical Research Scotland. Grant Number: 436FR
A weight initialization method based on neural network with asymmetric activation function
Get PDFYesWeight initialization of neural networks has an important influence on the learning process, and the selection of initial weights is related to the activation interval of the activation function. It is proposed that an improved and extended weight initialization method for neural network with asymmetric activation function as an extension of the linear interval tolerance method (LIT), called ‘GLIT' (generalized LIT), which is more suitable for higher-dimensional inputs. The purpose is to expand the selection range of the activation function so that the input falls in the unsaturated region, so as to improve the performance of the network. Then, a tolerance solution theorem based upon neural network system is given and proved. Furthermore, the algorithm is given about determining the initial weight interval. The validity of the theorem
and algorithm is verified by numerical experiments. The input could fall into any preset interval in the sense of probability under the GLIT method. In another sense, the GLIT method could provide a theoretical basis for the further study of neural networks.National Science Foundation of China under Grants (62073226, 61603262), Liaoning Province Natural Science Foundation (2020-KF-11-09, 2021-KF-11-05), Shen-Fu Demonstration Zone Science and Technology Plan Project (2020JH13, 2021JH07), Central Government Guides Local Science and Technology Development Funds of Liaoning Province (2021JH6)
Gender and smile dynamics
No full textNoThis chapter is concerned with the discussion of a computational framework to aid with gender classification in an automated fashion using the dynamics of a smile. The computational smile dynamics framework we discuss here uses the spatio-temporal changes on the face during a smile. Specifically, it uses a set of spatial and temporal features on the overall face. These include the changes in the area of the mouth, the geometric flow around facial features and a set of intrinsic features over the face. These features are explicitly derived from the dynamics of the smile. Based on it, a number of distinct dynamic smile parameters can be extracted which can then be fed to a machine learning algorithm for gender classification
There is Power in the Past: The Politicization of Archaeology and Heritage in the Star Wars Universe
Get PDFYesHeritage (and by extension, archaeology) is an important part of the Star Wars universe. Both the Jedi and the Sith share teachings revolving around sites and artifacts important to their heritage and identities, and archaeologists like Chelli Aphra have played important roles in the development and maintenance of heritage. However, the politicization of sites and artifacts by many groups and individuals has also served as motivation behind significant schisms, battles, imperialism, and resistance. As professional archaeologists, we have become familiar with the ways these themes are appearing within our real world discipline as well. This paper will broadly examine the roles that archaeology and heritage play in the Star Wars universe. Using examples from both canon media and expanded universe (now referred to as Legends) lore, this paper will explore the ways in which political factions manipulate and weaponize heritage and archaeology to their benefit. These examples will then be discussed within real world contexts to illustrate how Star Wars is ultimately a perfect encapsulation of the political powers inherent in archaeology and heritage studies, and the resistance to the manipulation of these fields
The Use of Function Modelling Methods in Industry: Insights from a Large Scale Study with an Automotive OEM
Get PDFYesThis paper presents an evaluation study for the System State Flow Diagram function modeling framework
based on a large-scale study with an automotive OEM. Technical reports are used to evaluate the usage of
the framework within the organization. The paper also introduces a list of the type of problems that
engineers are interested in in practical function modelling. The findings suggest that there is a widespread
uptake of the framework across the organization and it supports the usage of relevant key engineering tools
within the context of a broader model-based Failure Mode Analysis methodology
Team-Based Learning Approach for the Delivery of Over-the-counter Module in the Faculty of Pharmacy in Jordan
Get PDFYesTeam-based learning is an active learning strategy that focuses on student’s engagement, development of critical thinking, and transferable skills needed in the workplace. While many pharmacy faculties around the world have applied team-based learning into their curriculums, the implementation of team-based learning into the Middle East is still in the experimental phase and poses its own challenges. This reflective statement elaborates on our experience and feedback of implementing team-based learning for the first time at the pharmacy faculty of Zarqa University in Jordan through the delivery of over-the-counter module
Positive experiences in dementia care-giving: findings from the IDEAL programme
Get PDFYesThere is a growing evidence base that identifying positive experiences in providing care can have a beneficial influence on carer wellbeing. However, there is a need to better understand what carers identify as the positive aspects of care-giving. The aim of this study is to explore the satisfying aspects of providing care to people with dementia. This study utilised Time 1 data from 1,277 carers of people in the mild-to-moderate stages of dementia taking part in the IDEAL (Improving the experience of Dementia and Enhancing Active Life) cohort study. Responses from 900 carers who answered the open-ended question ‘What is your greatest satisfaction in caring for your relative/friend?’ were analysed using thematic analysis. From the responses, 839 carers detailed satisfactions. Eight themes were identified, pertaining to three groups of beneficiaries: carers, people with dementia and the dyad. Perceived benefits for carers included identifying aspects of personal growth, seeing glimpses of the person, feeling they were making a difference and doing their duty. For the person with dementia, these included retaining independence, receiving good quality care and being happy. Dyadic benefits concerned the continuation of the relationship between carer and person with dementia. The findings highlight the need to take a dyadic approach when conceptualising positive experiences in providing care. Further research is needed to understand the role these positive experiences play and to develop interventions. Professionals working with carers should identify and validate these experiences.‘Improving the experience of Dementia and Enhancing Active Life: living well with dementia. The IDEAL study’ was funded jointly by the Economic and Social Research Council (ESRC) and the National Institute for Health and Care Research (NIHR) (grant number ES/L001853/2); ‘Improving the experience of Dementia and Enhancing Active Life: a longitudinal perspective on living well with dementia. The IDEAL-2 study’ is funded by the Alzheimer's Society (grant number 348, AS-PR2-16-001
Biomedical applications of MXene-integrated composites: regenerative medicine, infection therapy, cancer treatment, and biosensing
Get PDFYesMXenes (viz., transition metal carbides, carbonitrides, and nitrides) have
emerged as a new subclass of 2D materials. Due to their outstanding physicochemical
and biological properties, MXenes have gained much attention
in the biomedical field in recent years, including drug delivery systems,
regenerative medicine, and biosensing. Additionally, the incorporation
of MXenes into hydrogels has garnered significant interest in biomedical
engineering as an electroactive and mechanical nanoreinforcer capable of
converting nonconductive scaffolds into excellent conductors of electricity
with an impressive effect on mechanical properties for the engineering of
electroactive organs and tissues such as cardiac, skeletal muscle, and nerve.
However, many questions and problems remain unresolved that need to be
answered to usher these 2D materials toward their true destiny. Thus, this
review paper aims to provide an overview of the design and applications of
MXene-integrated composites for biomedical applications, including cardiac
tissue engineering, wound healing, infection therapy, cancer therapy, and
biosensors. Moreover, the current challenges and limitations of utilizing
MXenes in vivo are highlighted and discussed, followed by its prospects
as a guideline toward possible various futuristic biomedical applications.
This review article will inspire researchers, who search for properties,
opportunities, and challenges of using this 2D nanomaterial in biomedical
applications.MXenes (viz., transition metal carbides, carbonitrides, and nitrides) have
emerged as a new subclass of 2D materials. Due to their outstanding physicochemical
and biological properties, MXenes have gained much attention
in the biomedical field in recent years, including drug delivery systems,
regenerative medicine, and biosensing. Additionally, the incorporation
of MXenes into hydrogels has garnered significant interest in biomedical
engineering as an electroactive and mechanical nanoreinforcer capable of
converting nonconductive scaffolds into excellent conductors of electricity
with an impressive effect on mechanical properties for the engineering of
electroactive organs and tissues such as cardiac, skeletal muscle, and nerve.
However, many questions and problems remain unresolved that need to be
answered to usher these 2D materials toward their true destiny. Thus, this
review paper aims to provide an overview of the design and applications of
MXene-integrated composites for biomedical applications, including cardiac
tissue engineering, wound healing, infection therapy, cancer therapy, and
biosensors. Moreover, the current challenges and limitations of utilizing
MXenes in vivo are highlighted and discussed, followed by its prospects
as a guideline toward possible various futuristic biomedical applications.
This review article will inspire researchers, who search for properties,
opportunities, and challenges of using this 2D nanomaterial in biomedical
applications
Single-Element and MIMO Circularly Polarized Microstrip Antennas with Negligible Back Radiation for 5G Mid-Band Handsets
Get PDFYesIn this paper, single-element and MIMO microstrip antenna with two pairs of unequal slits is proposed as a circularly polarized antenna with negligible back radiation for 5G mid-band handsets. The unequal pairs of slits are engraved on the antenna patch to guarantee the presence of the circular polarization (CP). The proximity-coupled feeding technique is used to excite the proposed microstrip antenna in order to provide larger antenna -10 dB bandwidth which approaches 10.8% (3.48-3.87 GHz). A novel analysis technique is proposed in this paper that demonstrates the 3D axial ratio pattern in order to generate CP in the broadside direction without affecting the structure of the ground plane which ensures weak back radiation. The 3 dB axial ratio bandwidth (ARBW) is found to be equal to 4.1% extended along the range (3.58-3.73 GHz). To make the design more compatible with the 5G mid-band handsets, the 2 × 2 MIMO structure of the proposed antenna with reduced mutual coupling (less than -20 dB) is also presented in this work. The simulation and measured results are in good agreement, and both verify the CP characteristics and the weak back radiation of the proposed antenna.British Council “2019 UK-China-BRI Countries Partnership Initiative Programme” with project titled “Adapting to Industry 4.0 Oriented International Education and Research Collaboration”
The development of a liposomal form Secukinumab – an IL 17 pathway inhibitor in the treatment of psoriasis
No full textVarious approaches are currently used to treat and manage psoriasis, and biological treatments are
often the latest approaches. All biological treatments have major side effects as they are given
systemically via injections. One of the latest biological treatments for psoriasis, one which has
shown great efficacy with fewer side effects, is Secukinumab. Secukinumab is an anti-IL17
antibody that works by stopping the action of IL17, a cytokine that is known to have a major role
in the pathogenesis of psoriasis. This work is based on the development of a new way to commence
drug therapy to reduce the side effects of the treatment.
Our work is based on the studies of the genotoxicity of the drug Secukinumab in its bulk and
liposome form using comet and micronucleus assays on lymphocytes. The results from both assays
have illustrated the safety of the drug and demonstrated the reduction of the DNA damage induced
in both healthy individuals and patients with psoriasis. Secukinumab significantly decreases-H2O2 induced damage and efficiently attenuates its adverse effects both in the comet (p<0.0001) and
micronucleus assays (p<0.01). The two concentrations of Secukinumab used (2.1 and 2.8μg/ml)
efficiently decreased H2O2-induced DNA damage in both groups to nearly the level of the negative
control. Overall, Secukinumab reveals protective and anti-genotoxic effects by demonstrating its potential in reducing DNA damage caused by oxidative stress and by not inducing any further
damage in the lymphocytes of either healthy individuals or patients. Liposomes are highly versatile
which have been proven efficient for therapy and research applications. The discovery of new
therapies in the treatment of psoriasis is a considerable challenge and is now a necessity. Our study
was the first one to determine the genotoxicity of various concentrations of the drug in the
lymphocytes of psoriasis patients compared to healthy individuals. In the MTT assay, the data
showed a decrease in % cell survival rates after exposure to different concentrations of
Secukinumab. Also, the results demonstrated no statistically significant differences on
confounding factors such as ethnicity, smoking, drinking habits, gender and age among psoriasis
patient and healthy controls. The regulation of gene expression levels of IL-17, IL-22 and RORC
were assessed after treatment with Secukinumab in the bulk and liposome form via RT-PCR analysis. Secukinumab bulk (2.1μg/ml) treatment significantly down-regulated gene expression of
IL-17, IL22 and RORC to 0.46-fold, 0.47-fold and 0.5-fold, respectively. However, Secukinumab
liposome (2.1μg/ml) only decreased the expression of IL-17 and IL-22 significantly, by 0.46-fold
and 0.53-fold, respectively. On the other hand, studying the expression of P53 and P21 using
qPCR revealed that Secukinumab bulk and liposome has no effect on the expression of these genes
in lymphocytes from healthy individuals and psoriasis patients.
Western blotting was used to investigate the effect of Secukinumab in both forms on protein
expression levels IL-17, IL-22 and RORC. Analysis of the results showed that Secukinumab bulk
and liposome had no significant effect on expression levels of any of these proteins in lymphocytes
derived from healthy individuals. However, there was a statistically significant down-regulation
observed in the protein expression levels of IL-17, IL-22 and RORC in lymphocytes obtained from the psoriasis patients, confirming the sensitivity of the compromised lymphocytes from patient group to Secukinumab treatment. With Secukinumab (bulk form) administration, a 0.5-fold
decrease was observed in IL-17, 0.59-fold decrease in IL-22, and a 0.6-fold decrease in RORC
expression. However, liposome form reduced their levels to 0.47–fold, 0.5-fold and 0.47–fold,
respectively, when compared to the control group. While it had no significant effect on expression
of P53 and P21 proteins in lymphocytes from healthy individuals and psoriasis patients and there
was no difference observed in their regulation. In conclusion, the use of Secukinumab liposome as
topical drug delivery system may be suitable replacement for improving the drug bioavailability
and its side effects.Libyan Cultural Attaché and Libyan embass