56 research outputs found
Teachers' perceptions about using serious games in formal education in Jordan:Possibilities and limitations
Targeting proinsulin to local immune cells using an intradermal microneedle delivery system; a potential antigen-specific immunotherapy for type 1 diabetes
Antigen-specific immunotherapy (ASI) has been proposed as an alternative treatment strategy for type 1 diabetes (T1D). ASI aims to induce a regulatory, rather than stimulatory, immune response in order to reduce, or prevent, autoimmune mediated β-cell destruction, thus preserving endogenous insulin production. The abundance of immunocompetent antigen presenting cells (APCs) within the skin makes this organ an attractive target for immunotherapies. Microneedles (MNs) have been proposed as a suitable drug delivery system to facilitate intradermal delivery of autoantigens in a minimally invasive manner. However, studies to date have employed single peptide autoantigens, which would restrict ASI to patients expressing specific Human Leukocyte Antigen (HLA) molecules, thus stratifying the patient population. This study aims to develop, for the first time, an intradermal MN delivery system to target proinsulin, a large multi-epitope protein capable of inducing tolerance in a heterogenous (in terms of HLA status) population of T1D patients, to the immunocompetent cells of the skin. An optimized three component coating formulation containing proinsulin, a diluent and a surfactant, facilitated uniform and reproducible coating of >30 μg of the active pharmaceutical ingredient on a stainless steel MN array consisting of thirty 500 μm projections. When applied to a murine model these proinsulin-coated MNs efficiently punctured the skin and after a limited insertion time (150 s) a significant proportion of the therapeutic payload (86%) was reproducibly delivered into the local tissue. Localized delivery of proinsulin in non-obese diabetic (NOD) mice using the coated MN system stimulated significantly greater proliferation of adoptively transferred antigen-specific CD8+ T cells in the skin draining lymph nodes compared to a conventional intradermal injection. This provides evidence of targeted delivery of the multi-epitope proinsulin antigen to skin-resident APCs, in vivo, in a form that enables antigen presentation to antigen-specific T cells in the local lymph nodes. The development of an innovative coated MN system for highly targeted and reproducible delivery of proinsulin to local immune cells warrants further evaluation to determine translation to a tolerogenic clinical outcome
Time-dependent mechanical behavior of human amnion: Macroscopic and microscopic characterization
Characterizing the mechanical response of the human amnion is essential to understand and to eventually prevent premature rupture of fetal membranes. In this study, a large set of macroscopic and microscopic mechanical tests have been carried out on fresh unfixed amnion to gain insight into the time-dependent material response and the underlying mechanisms. Creep and relaxation responses of amnion were characterized in macroscopic uniaxial tension, biaxial tension and inflation configurations. For the first time, these experiments were complemented by microstructural information from nonlinear laser scanning microscopy performed during in situ uniaxial relaxation tests. The amnion showed large tension reduction during relaxation and small inelastic strain accumulation in creep. The short-term relaxation response was related to a concomitant in-plane and out-of-plane contraction, and was dependent on the testing configuration. The microscopic investigation revealed a large volume reduction at the beginning, but no change of volume was measured long-term during relaxation. Tension–strain curves normalized with respect to the maximum strain were highly repeatable in all configurations and allowed the quantification of corresponding characteristic parameters. The present data indicate that dissipative behavior of human amnion is related to two mechanisms: (i) volume reduction due to water outflow (up to ∼20 s) and (ii) long-term dissipative behavior without macroscopic deformation and no systematic global reorientation of collagen fibers
Microneedle delivery of antigen-specific immunotherapy for Type 1 diabetes
Antigen-specific immunotherapy (ASI) involves induction of tolerance to
autoantigens. An important protein in the development of type 1 diabetes (T1D)
is the autoantigen, proinsulin (PI), the precursor of insulin. Microneedles (MNs)
are micron-sized needles that penetrate into the upper skin layers. MNs provide
advantages for autoantigen delivery including targeted delivery to the skin’s
dendritic cells (DCs), with minimal inflammation. The aim of this Thesis was to
develop a PI-coated solid MN system and investigate the potential of this
system to induce peripheral tolerance in the non-obese diabetic (NOD) mouse
model of T1D.
A highly concentrated PI MN coating formulation was developed containing the
PI, diluent and a surfactant. The formulation enabled uniform and reproducible
coating of the PI on to MNs. Delivery of PI from the MN system was
investigated in mouse skin. MN application method and duration were optimised
and resulted in skin puncture and reproducible delivery of PI to the skin.
In vitro studies identified the insulin-reactive G9 CD8+ T cell as an appropriate
biological readout for PI delivery. In vivo delivery studies indicated that MNdelivered
PI was delivered to the skin and subsequently processed by DCs into
PI peptides, which were cross-presented in the skin draining lymph nodes to
adoptively transferred G9 CD8+ T cells. This demonstrated that the PI-coated
MN system has potential for inducing peripheral tolerance in the NOD mouse.
T1D development was significantly delayed in NOD SCID mice that received
cells from PI-treated NOD mice and cells from diabetic NOD mice (experimental
group). However, no statistically significant difference in time to T1D
development was observed between the experimental group and the control
NOD SCID mice that received cells from untreated NOD mice and diabetic NOD
mice. Further investigation of the dosage and dosing frequency of PI using the
coated MN system is, therefore, warranted
Effectiveness of Inactive Models in Acquiring Mathematical Concepts to Students in the Basic Stage and Reflective Thinking
The Role of Planning in Enhancing Heritage Tourism in Palestine: Jericho City- Case Study
Tourism is considered one of the basic pillars in the global economy. Most of countries seek
through developing their tourism sector as a main supporter to their national income. Tourism in
Palestine varies in its forms and characteristics according to the religious and historical status
which it occupies. In addition, Palestine has a huge variety in its natural characteristics. The
archaeological sites in Palestine form the corner stone in the field of the archaeological tourism
and in the economy of the Palestinian tourism. It should be emphasized that the Palestinian
sector faces many obstacles and challenges represented in. the little concern which the
government pays towards archaeological sector and the poor urban planning. This led to the
negative effect on archaeological tourism in Palestine. The study aims at analyzing the urban
planning in Palestine, the laws and regulations in regard of protecting the Palestinian
archaeological sites. The relation between the urban planning and the archeological sites will be
reviewed by studying the policies, the strategies and the local and national planning. In addition ،
the views of the planners and the activists who in relation with the archaeological tourism will be
analyzed added to analyzing the resent status for the borders of Jericho municipality. A new
strategy will be suggested that could protect the archaeological sites and clarify its historical and
economic importance. The archaeological tourism in Palestine has its own flavor and is
distinguished from any other tourism in the world since it forms the identity of the Palestinian
people
The Iranian foreign policy with regard to Arab-Israeli conflict “The Palestinian Issue”, 1979/2011
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