Search results for: stem cell transplant
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4133

Search results for: stem cell transplant

3893 Comparison of Cardiomyogenic Potential of Amniotic Fluid Mesenchymal Stromal Cells Derived from Normal and Isolated Congenital Heart Defective Fetuses

Authors: Manali Jain, Neeta Singh, Raunaq Fatima, Soniya Nityanand, Mandakini Pradhan, Chandra Prakash Chaturvedi

Abstract:

Isolated Congenital Heart Defect (ICHD) is the major cause of neonatal death worldwide among all forms of CHDs. A significant proportion of fetuses with ICHD die in the neonatal period if no treatment is provided. Recently, stem cell therapies have emerged as a potential approach to ameliorate ICHD in children. ICHD is characterized by cardiac structural abnormalities during embryogenesis due to alterations in the cardiomyogenic properties of a pool of cardiac progenitors/ stem cells associated with fetal heart development. The stem cells present in the amniotic fluid (AF) are of fetal origin and may reflect the physiological and pathological changes in the fetus during embryogenesis. Therefore, in the present study, the cardiomyogenic potential of AF-MSCs derived from fetuses with ICHD (ICHD AF-MSCs) has been evaluated and compared with that of AF-MSCs of structurally normal fetuses (normal AF-MSCs). Normal and ICHD AF-MSC were analyzed for the expression of cardiac progenitor markers viz., stage-specific embryonic antigen-1 (SSEA-1), vascular endothelial growth factor 2 (VEGFR-2) and platelet-derived growth factor receptor-alpha (PDGFR-α) by flow cytometry. The immunophenotypic characterization revealed that ICHD AF-MSCs have significantly lower expression of cardiac progenitor markers VEGFR-2 (0.14% ± 0.6 vs.48.80% ± 0.9; p <0.01), SSEA-1 (70.86% ± 2.4 vs. 88.36% ±2.7; p <0.01), and PDGFR-α (3.92% ± 1.8 vs. 47.59% ± 3.09; p <0.01) in comparison to normal AF-MSCs. Upon induction with 5’-azacytidine for 21 days, ICHD AF-MSCs showed a significantly down-regulated expression of cardiac transcription factors such as GATA-4 (0.4 ± 0.1 vs. 6.8 ± 1.2; p<0.01), ISL-1 (2.3± 0.6 vs. 14.3 ± 1.12; p<0.01), NK-x 2-5 (1.1 ± 0.3 vs. 14.1 ±2.8; p<0.01), TBX-5 (0.4 ± 0.07 vs. 4.4 ± 0.3; p<0.001), and TBX-18 (1.3 ± 0.2 vs. 4.19 ± 0.3; p<0.01) when compared with the normal AF-MSCs. Furthermore, immunocytochemical staining revealed that both types of AF-MSCs could differentiate into cardiovascular lineages and express cardiomyogenic, endothelial, and smooth muscle actin markers, viz., cardiac troponin (cTNT), CD31, and alpha-smooth muscle actin (α-SMA). However, normal AF-MSCs showed an enhanced expression of cTNT (p<0.001), CD31 (p<0.01), and α-SMA (p<0.05), compared to ICHD AF-MSCs. Overall, these results suggest that the ICHD-AF-MSCs have a defective cardiomyogenic differentiation potential and that the defects in these stem cells may have a role in the pathogenesis of ICHD.

Keywords: amniotic fluid, cardiomyogenic potential, isolated congenital heart defect, mesenchymal stem cells

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3892 Suppression of Immunostimulatory Function of Dendritic Cells and Prolongation of Skin Allograft Survival by Dryocrassin

Authors: Hsin-Lien Lin, Ju-Hui Fu

Abstract:

Dendritic cells (DCs) are the major professional antigen-presenting cells for the development of optimal T-cell immunity. DCs can be used as pharmacological targets to screen novel biological modifiers for the treatment of harmful immune responses, such as transplantation rejection. Dryopteris crassirhizoma Nakai (Aspiadaceae) is used for traditional herbal medicine in the region of East Asia. The root of this fern plant has been listed for treating inflammatory diseases. Dryocrassin is the tetrameric phlorophenone component derived from Dryopteris. Here, we tested the immunomodulatory potential of dryocrassin on lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs in vitro and in skin allograft transplantation in vivo. Results demonstrated that dryocrassin reduced the secretion of tumor necrosis factor-α, interleukin-6, and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility complex class II, CD40, and CD86 on DCs was also blocked by dryocrassin. Moreover, LPS-stimulated DC-elicited allogeneic T-cell proliferation was lessened by dryocrassin. In addition, dryocrassin inhibited LPS-induced activation of IϰB kinase, JNK/p38 mitogen-activated protein kinase, as well as the translocation of NF-ϰB. Treatment with dryocrassin obviously diminished 2,4-dinitro-1-fluorobenzene- induced delayed-type hypersensitivity and prolonged skin allograft survival. Dryocrassin may be one of the potent immunosuppressive agents for transplant rejection through the destruction of DC maturation and function.

Keywords: dryocrassin, dendritic cells, immunosuppression, skin allograft

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3891 The Influence of Cultural Perceptions in the Preference and Choice of STEM Programs

Authors: Priscilla Adoley Moffat

Abstract:

This study explored perceptions rooted in and acquired from the cultures of many developing countries and how they impact applicants’ preferences and choices of STEM programs. The context of developing countries was chosen for this study because gender role socialization continues to maintain an important place in most of these cultures. This study’s relevance rests in the fact that, as the world takes steps to encourage and promote the choice and study of STEM programs, especially among females, there is a need for efforts towards understanding various cultural perceptions towards some programs of study, particularly STEM programs, which have diverse gender attributions in many developing cultures. Also, as the world strives to achieve gender equity in education, such a study comes in handy, as it provides a useful understanding of the underlying cultural factors that affect study program preferences of applicants, particularly in developing countries like Ghana as well as others in Africa. The study analyzed the admission application data of five public universities in Ghana. 1600 randomly-sampled final-year students of 32 randomly-selected senior high schools from the 16 regions of Ghana were interviewed. Since parents and teachers often guide and influence the study program choices of applicants, the study examined the perceptions of 180 teachers and 360 parents. The study found, among other things, that STEM programs are commonly perceived to pose much more difficulty to females than they do to males. As a result, many female applicants are discouraged from choosing these programs. While nursing programs are perceived more as programs for females, with the justification that females are better caregivers, males are perceived to be better medical doctors, engineers, and computer technicians. Thus, many females are less encouraged to choose Technology and Engineering programs.

Keywords: culture, perceptions, STEM, choice, preference

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3890 Chemotactic Behaviour of Human Mesenchymal Stem Cells in Response to Silicate Substituted Hydroxyapatite

Authors: Dinara Ikramova, Karin A. Hing, Simon C. F. Rawlinson

Abstract:

Silicate-substituted hydroxyapatite (SiHA) has been shown to enhance bone regeneration in vivo compared with phase pure stoichiometric hydroxyapatite. Evidence suggests that substrate chemistry dependent formation of a permissive protein layer on the surface of synthetic bone graft substitute materials is key for bioactivity and cell attachment. However, little information is available on whether the substrate chemistry may affect cell migration and recruitment. The aim of this study is to investigate whether or not human Mesenchymal Stem Cells (hMSCs) exhibit a chemotactic response to SiHA porous granules and if it can be linked to either the ion exchange or protein sequestering and enrichment on the surface of the material. 150mg of SiHA granules with 80% total porosity and 20% strut porosity were incubated in 1ml of either Serum Free Media (SFM) or 10% Serum Containing Media (SCM) under static cell culture conditions (37°C, 5% CO2) in absence of cells. Protein sequestering and exchange of calcium, phosphate and silicate ions were analysed at 0.5, 1, 2, 4, 8, 16 and 24 hours with n=12 per time point. Migration of hMSCs in the presence of 150mg of SiHA granules was assessed over 24 hours using a modified transwell migration system in either SFM or SCM (n=6) with 30% serum containing media acting as a positive control. At 24 hours protein sequestering and ionic exchange were analysed, and the number of cells was quantified using a high throughput confocal microscope (IN Cell Analyser 6000). In acellular condition, both calcium and phosphate ion concentrations in media showed a decrease at 24 hours which was greater in SFM than in SCM. This suggests possible formation and precipitation of a bone like apatite on the surface of SiHA. Reduction in this activity observed in SCM indicates that the presence of serum proteins is interfering with the ion exchange at the material and media interface. Adsorbed protein levels showed fluctuation over time followed by sharp decrease at 24 hours, suggesting a possible protein rearrangement on the surface of the material. The ion analysis performed on SFM and SCM after 24-hour incubation with cells in the presence of granules showed a greater reduction in phosphate concentration in both SFM and SCM compared to phosphate levels in acellular condition. Silicate concentration in SCM increased from 1.6mM (absence of cells) to 5.1mM (presence of cells). This indicates that the cells are promoting the uptake of phosphate and release of silicate ions. No significant change was seen in levels of adsorbed proteins in the presence and absence of cells. Further analysis is required to determine whether the species of these proteins change over time. The analysis of cell migration after 24-hour incubation showed more cells migrating towards the granules, 12.7% in SFM and 8.3% in SCM, than in positive control, 4.5% in SFM and 3.6% in SCM respectively. These results suggest that SiHA has a chemotactic activity independent of serum proteins. A property which has not previously been demonstrated for a synthetic bone graft material.

Keywords: cell migration, hMSCs, SiHA, transwell migration system

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3889 Synthesis and Application of Oligosaccharides Representing Plant Cell Wall Polysaccharides

Authors: Mads H. Clausen

Abstract:

Plant cell walls are structurally complex and contain a larger number of diverse carbohydrate polymers. These plant fibers are a highly valuable bio-resource and the focus of food, energy and health research. We are interested in studying the interplay of plant cell wall carbohydrates with proteins such as enzymes, cell surface lectins and antibodies. However, detailed molecular level investigations of such interactions are hampered by the heterogeneity and diversity of the polymers of interest. To circumvent this, we target well-defined oligosaccharides with representative structures that can be used for characterizing protein-carbohydrate binding. The presentation will highlight chemical syntheses of plant cell wall oligosaccharides from our group and provide examples from studies of their interactions with proteins.

Keywords: oligosaccharides, carbohydrate chemistry, plant cell walls, carbohydrate-acting enzymes

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3888 STEM (Science–Technology–Engineering–Mathematics) Based Entrepreneurship Training, Within a Learning Company

Authors: Diana Mitova, Krassimir Mitrev

Abstract:

To prepare the current generation for the future, education systems need to change. It implies a way of learning that meets the demands of the times and the environment in which we live. Productive interaction in the educational process implies an interactive learning environment and the possibility of personal development of learners based on communication and mutual dialogue, cooperation and good partnership in decision-making. Students need not only theoretical knowledge, but transferable skills that will help them to become inventors and entrepreneurs, to implement ideas. STEM education , is now a real necessity for the modern school. Through learning in a "learning company", students master examples from classroom practice, simulate real life situations, group activities and apply basic interactive learning strategies and techniques. The learning company is the subject of this study, reduced to entrepreneurship training in STEM - technologies that encourage students to think outside the traditional box. STEM learning focuses the teacher's efforts on modeling entrepreneurial thinking and behavior in students and helping them solve problems in the world of business and entrepreneurship. Learning based on the implementation of various STEM projects in extracurricular activities, experiential learning, and an interdisciplinary approach are means by which educators better connect the local community and private businesses. Learners learn to be creative, experiment and take risks and work in teams - the leading characteristics of any innovator and future entrepreneur. This article presents some European policies on STEM and entrepreneurship education. It also shares best practices for training company training , with the integration of STEM in the learning company training environment. The main results boil down to identifying some advantages and problems in STEM entrepreneurship education. The benefits of using integrative approaches to teach STEM within a training company are identified, as well as the positive effects of project-based learning in a training company using STEM. Best practices for teaching entrepreneurship through extracurricular activities using STEM within a training company are shared. The following research methods are applied in this research paper: Theoretical and comparative analysis of principles and policies of European Union countries and Bulgaria in the field of entrepreneurship education through a training company. Experiences in entrepreneurship education through extracurricular activities with STEM application within a training company are shared. A questionnaire survey to investigate the motivation of secondary vocational school students to learn entrepreneurship through a training company and their readiness to start their own business after completing their education. Within the framework of learning through a "learning company" with the integration of STEM, the activity of the teacher-facilitator includes the methods: counseling, supervising and advising students during work. The expectation is that students acquire the key competence "initiative and entrepreneurship" and that the cooperation between the vocational education system and the business in Bulgaria is more effective.

Keywords: STEM, entrepreneurship, training company, extracurricular activities

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3887 Structural Evaluation of Cell-Filled Pavement

Authors: Subrat Roy

Abstract:

This paper describes the findings of a study carried out for evaluating the performance of cell-filled pavement for low volume roads. Details of laboratory investigations and the methodology adopted for construction of cell-filled pavement are presented. The aim of this study is to evaluate the structural behaviour of cement concrete filled cell pavement laid over three different types of subbases (water bound macadam, soil-cement and moorum). A formwork of cells of a thin plastic sheet was used to construct the cell-filled pavements to form flexible, interlocked block pavements. Surface deflections were measured using falling weight deflectometer and benkelman beam methods. Resilient moduli of pavement layers were estimated from the measured deflections. A comparison of deflections obtained from both the methodology is also presented.

Keywords: cell-filled pavement, WBM, FWD, Moorum

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3886 Electrospinning of Nanofibrous Meshes and Surface-Modification for Biomedical Application

Authors: Hyuk Sang Yoo, Young Ju Son, Wei Mao, Myung Gu Kang, Sol Lee

Abstract:

Biomedical applications of electrospun nanofibrous meshes have been received tremendous attentions because of their unique structures and versatilities as biomaterials. Incorporation of growth factors in fibrous meshes can be performed by surface-modification and encapsulation. Those growth factors stimulate differentiation and proliferation of specific types of cells and thus lead tissue regenerations of specific cell types. Topographical cues of electrospun nanofibrous meshes also increase differentiation of specific cell types according to alignments of fibrous structures. Wound healing treatments of diabetic ulcers were performed using nanofibrous meshes encapsulating multiple growth factors. Aligned nanofibrous meshes and those with random configuration were compared for differentiating mesenchymal stem cells into neuronal cells. Thus, nanofibrous meshes can be applied to drug delivery carriers and matrix for promoting cellular proliferation.

Keywords: nanofiber, tissue, mesh, drug

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3885 The Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) Process: An Audit of Its Utilisation on a UK Tertiary Specialist Intensive Care Unit

Authors: Gokulan Vethanayakam, Daniel Aston

Abstract:

Introduction: The ReSPECT process supports healthcare professionals when making patient-centered decisions in the event of an emergency. It has been widely adopted by the NHS in England and allows patients to express thoughts and wishes about treatments and outcomes that they consider acceptable. It includes (but is not limited to) cardiopulmonary resuscitation decisions. ReSPECT conversations should ideally occur prior to ICU admission and should be documented in the eight sections of the nationally-standardised ReSPECT form. This audit evaluated the use of ReSPECT on a busy cardiothoracic ICU in an NHS Trust where established policies advocating its use exist. Methods: This audit was a retrospective review of ReSPECT forms for a sample of high-risk patients admitted to ICU at the Royal Papworth Hospital between January 2021 and March 2022. Patients all received one of the following interventions: Veno-Venous Extra-Corporeal Membrane Oxygenation (VV-ECMO) for severe respiratory failure (retrieved via the national ECMO service); cardiac or pulmonary transplantation-related surgical procedures (including organ transplants and Ventricular Assist Device (VAD) implantation); or elective non-transplant cardiac surgery. The quality of documentation on ReSPECT forms was evaluated using national standards and a graded ranking tool devised by the authors which was used to assess narrative aspects of the forms. Quality was ranked as A (excellent) to D (poor). Results: Of 230 patients (74 VV-ECMO, 104 transplant, 52 elective non-transplant surgery), 43 (18.7%) had a ReSPECT form and only one (0.43%) patient had a ReSPECT form completed prior to ICU admission. Of the 43 forms completed, 38 (88.4%) were completed due to the commencement of End of Life (EoL) care. No non-transplant surgical patients included in the audit had a ReSPECT form. There was documentation of balance of care (section 4a), CPR status (section 4c), capacity assessment (section 5), and patient involvement in completing the form (section 6a) on all 43 forms. Of the 34 patients assessed as lacking capacity to make decisions, only 22 (64.7%) had reasons documented. Other sections were variably completed; 29 (67.4%) forms had relevant background information included to a good standard (section 2a). Clinical guidance for the patient (section 4b) was given in 25 (58.1%), of which 11 stated the rationale that underpinned it. Seven forms (16.3%) contained information in an inappropriate section. In a comparison of ReSPECT forms completed ahead of an EoL trigger with those completed when EoL care began, there was a higher number of entries in section 3 (considering patient’s values/fears) that were assessed at grades A-B in the former group (p = 0.014), suggesting higher quality. Similarly, forms from the transplant group contained higher quality information in section 3 than those from the VV-ECMO group (p = 0.0005). Conclusions: Utilisation of the ReSPECT process in high-risk patients is yet to be well-adopted in this trust. Teams who meet patients before hospital admission for transplant or high-risk surgery should be encouraged to engage with the ReSPECT process at this point in the patient's journey. VV-ECMO retrieval teams should consider ReSPECT conversations with patients’ relatives at the time of retrieval.

Keywords: audit, critical care, end of life, ICU, ReSPECT, resuscitation

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3884 Biocompatible Porous Titanium Scaffolds Produced Using a Novel Space Holder Technique

Authors: Yunhui Chen, Damon Kent, Matthew Dargusch

Abstract:

Synthetic scaffolds are a highly promising new approach to replace both autografts and allografts to repair and remodel damaged bone tissue. Biocompatible porous titanium scaffold was manufactured through a powder metallurgy approach. Magnesium powder was used as space holder material which was compacted with titanium powder and removed during sintering. Evaluation of the porosity and mechanical properties showed a high level of compatibility with human bone. Interconnectivity between pores is higher than 95% for porosity as low as 30%. The elastic moduli are 39 GPa, 16 GPa and 9 GPa for 30%, 40% and 50% porosity samples which match well to that of natural bone (4-30 GPa). The yield strengths for 30% and 40% porosity samples of 315 MPa and 175 MPa are superior to that of human bone (130-180 MPa). In-vitro cell culture tests on the scaffold samples using Human Mesenchymal Stem Cells (hMSCs) demonstrated their biocompatibility and indicated osseointegration potential. The scaffolds allowed cells to adhere and spread both on the surface and inside the pore structures. With increasing levels of porosity/interconnectivity, improved cell proliferation is obtained within the pores. It is concluded that samples with 30% porosity exhibit the best biocompatibility. The results suggest that porous titanium scaffolds generated using this manufacturing route have excellent potential for hard tissue engineering applications.

Keywords: scaffolds, MG-63 cell culture, titanium, space holder

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3883 Parental Monitoring of Learners’ Cell Phone Use in the Eastern Cape, South Africa

Authors: Melikhaya Skhephe, Robert Mawuli Kwasi Boadzo, Zanoxolo Berington Gobingca

Abstract:

This research study sought to examine parental monitoring of learners’ cell phone use in the Eastern Cape, South Africa. To this end, the researchers employed a quantitative approach. Data were obtained through questionnaires, with a sample of 15 parents having been purposively selected. The findings revealed that parents are unaware that they have to monitor the learner’s cell phone. Another finding was that parents in the 21-century did not support the use of mobile phones in education. The researchers recommend that parent’s discussion forums be created to educate parents on how a cell phone can be used in education. Cellphone companies need to be encouraged to educate parents on how they monitor cell phones used by learners. Another recommendation was that network providers need to restrict access to searching on the internet according to age.

Keywords: parental monitoring, app blocking services, learner’s cell phone use, cell phone

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3882 Mathematical Modeling of Cell Volume Alterations under Different Osmotic Conditions

Authors: Juliana A. Knocikova, Yann Bouret, Médéric Argentina, Laurent Counillon

Abstract:

Cell volume, together with membrane potential and intracellular hydrogen ion concentration, is an essential biophysical parameter for normal cellular activity. Cell volumes can be altered by osmotically active compounds and extracellular tonicity. In this study, a simple mathematical model of osmotically induced cell swelling and shrinking is presented. Emphasis is given to water diffusion across the membrane. The mathematical description of the cellular behavior consists in a system of coupled ordinary differential equations. We compare experimental data of cell volume alterations driven by differences in osmotic pressure with mathematical simulations under hypotonic and hypertonic conditions. Implications for a future model are also discussed.

Keywords: eukaryotic cell, mathematical modeling, osmosis, volume alterations

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3881 Dynamic Thermal Modelling of a PEMFC-Type Fuel Cell

Authors: Marco Avila Lopez, Hasnae Ait-Douchi, Silvia De Los Santos, Badr Eddine Lebrouhi, Pamela Ramírez Vidal

Abstract:

In the context of the energy transition, fuel cell technology has emerged as a solution for harnessing hydrogen energy and mitigating greenhouse gas emissions. An in-depth study was conducted on a PEMFC-type fuel cell, with an initiation of an analysis of its operational principles and constituent components. Subsequently, the modelling of the fuel cell was undertaken using the Python programming language, encompassing both steady-state and transient regimes. In the case of the steady-state regime, the physical and electrochemical phenomena occurring within the fuel cell were modelled, with the assumption of uniform temperature throughout all cell compartments. Parametric identification was carried out, resulting in a remarkable mean error of only 1.62% when the model results were compared to experimental data documented in the literature. The dynamic model that was developed enabled the scrutiny of the fuel cell's response in terms of temperature and voltage under varying current conditions.

Keywords: fuel cell, modelling, dynamic, thermal model, PEMFC

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3880 Intentional Relationship Building: Stem Faculty Perceptions of Culturally Responsive Mentoring

Authors: Niesha Douglas, Lisa Merriweather, Cathy Howell, Anna Sancyzk

Abstract:

Many studies explain that mentoring in an academic setting contributes to student success and retention. However, in the United States, where the population is diverse and filled with multiple ethnic groups, mentoring has become too generalized and fails to offer a unique individualized experience for underrepresented minorities (URM). The purpose of this paper is to describe the findings of an ongoing qualitative study that investigates the relationships among STEM doctoral faculty and URM students. Several faculty from three different predominately white institutions (PWI) in the Southeastern region of the United States were interviewed and engaged in open dialogue about their experiences with mentoring. The data collection included semi-structured interviews that took place in the classroom (pre-COVID-19) as well as virtually. The theoretical framework draws on the idea of Critical Race Theory and how cultural, social constructs interfere with effective mentoring for URM Doctoral STEM students. The findings in this study suggest that though the faculty and several years of experience mentoring students, there were some gaps in understanding the needs of URM students and how mentoring is a unique relationship that should be specialized for each student and should not fit into one mold.

Keywords: culture, critical race theory, mentoring, STEM

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3879 Single Cell Sorter Driven by Resonance Vibration of Cell Culture Substrate

Authors: Misa Nakao, Yuta Kurashina, Chikahiro Imashiro, Kenjiro Takemura

Abstract:

The Research Goal: With the growing demand for regenerative medicine, an effective mass cell culture process is required. In a repetitive subculture process for proliferating cells, preparing single cell suspension which does not contain any cell aggregates is highly required because cell aggregates often raise various undesirable phenomena, e.g., apoptosis and decrease of cell proliferation. Since cell aggregates often occur in cell suspension during conventional subculture processes, this study proposes a single cell sorter driven by a resonance vibration of a cell culture substrate. The Method and the Result: The single cell sorter is simply composed of a cell culture substrate and a glass pipe vertically placed against the cell culture substrate with a certain gap corresponding to a cell diameter. The cell culture substrate is made of biocompatible stainless steel with a piezoelectric ceramic disk glued to the bottom side. Applying AC voltage to the piezoelectric ceramic disk, an out-of-plane resonance vibration with a single nodal circle of the cell culture substrate can be excited at 5.5 kHz. By doing so, acoustic radiation force is emitted, and then cell suspension containing only single cells is pumped into the pipe and collected. This single cell sorter is effective to collect single cells selectively in spite of its quite simple structure. We collected C2C12 myoblast cell suspension by the single cell sorter with the vibration amplitude of 12 µmp-p and evaluated the ratio of single cells in number against the entire cells in the suspension. Additionally, we cultured the collected cells for 72 hrs and measured the number of cells after the cultivation in order to evaluate their proliferation. As a control sample, we also collected cell suspension by conventional pipetting, and evaluated the ratio of single cells and the number of cells after the 72-hour cultivation. The ratio of single cells in the cell suspension collected by the single cell sorter was 98.2%. This ratio was 9.6% higher than that collected by conventional pipetting (statistically significant). Moreover, the number of cells cultured for 72 hrs after the collection by the single cell sorter yielded statistically more cells than that collected by pipetting, resulting in a 13.6% increase in proliferated cells. These results suggest that the cell suspension collected by the single cell sorter driven by the resonance vibration hardly contains cell aggregates whose diameter is larger than the gap between the cell culture substrate and the pipe. Consequently, the cell suspension collected by the single cell sorter maintains high cell proliferation. Conclusions: In this study, we developed a single cell sorter capable of sorting and pumping single cells by a resonance vibration of a cell culture substrate. The experimental results show the single cell sorter collects single cell suspension which hardly contains cell aggregates. Furthermore, the collected cells show higher proliferation than that of cells collected by conventional pipetting. This means the resonance vibration of the cell culture substrate can benefit us with the increase in efficiency of mass cell culture process for clinical applications.

Keywords: acoustic radiation force, cell proliferation, regenerative medicine, resonance vibration, single cell sorter

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3878 Status and Management of Grape Stem Borer, Celosterna scrabrator with Soil Application of Chlorantraniliprole 0.4 gr

Authors: D. N. Kambrekar, S. B. Jagginavar, J. Aruna

Abstract:

Grape stem borer, Celosterna scrabrator is an important production constraint in grapes in India. Hitherto this pest was a severe menace only on the aged and unmanaged fields but during the recent past it has also started damaging the newly established fields. In India, since Karnataka, Andra Pradesh, Tamil Nadu and Maharashtra are the major grape production states, the incidence of stem borer is also restricted and severe in these states. The grubs of the beetle bore in to the main stem and even the branches, which affect the translocation of nutrients to the areal parts of the plant. Since, the grubs bore inside the stem, the chewed material along with its excreta is discharged outside the holes and the frass is found on the ground just below the bored holes. The portion of vines above the damaged part has a sticky appearance. The leaves become pale yellow which looks like a deficiency of micronutrients. The leaves ultimately dry and drop down. The status of the incidence of the grape stem borer in different grape growing districts of Northern Karnataka was carried out during three years. In each taluka five locations were surveyed for the incidence of grape stem borer. Further, the experiment on management of stem borer was carried out in the grape gardens of Vijayapur districts under farmers field during three years. Stem borer infested plants that show live holes were selected per treatments and it was replicated three times. Live and dead holes observed during pre-treatment were closely monitored and only plants with live holes were selected and tagged. Different doses of chlorantraniliprole 0.4% GR were incorporated into the soil around the vine basins near root zone surrounded to trunk region by removing soils up to 5-10 cm with a peripheral distance of 1 to 1.5 feet from the main trunk where feeder roots are present. Irrigation was followed after application of insecticide for proper incorporation of the test chemical. The results indicated that there was sever to moderate incidence of the stem borer in all the grape growing districts of northern Karnataka. Maximum incidence was recorded in Belagavi (11 holes per vine) and minimum was in Gadag district (8.5 holes per vine). The investigations carried out to study the efficacy of chlorantraniliprole on grape stem borer for successive three years under farmers field indicated that chlorantraniliprole @ 15g/vine applied just near the active root zone of the plant followed by irrigation has successfully managed the pest. The insecticide has translocated to all the parts of the plants and thereby stopped the activity of the pest which has resulted in to better growth of the plant and higher berry yield compared to other treatments under investigation. Thus, chlorantraniliprole 0.4 GR @ 15g/vine can be effective means in managing the stem borer.

Keywords: chlorantraniliprole, grape stem borer, Celosterna scrabrator, management

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3877 Evaluation of Important Transcription Factors and Kinases in Regulating the Signaling Pathways of Cancer Stem Cells With Low and High Proliferation Rate Derived From Colorectal Cancer

Authors: Mohammad Hossein Habibi, Atena Sadat Hosseini

Abstract:

Colorectal cancer is the third leading cause of cancer-related death in the world. Colorectal cancer screening, early detection, and treatment programs could benefit from the most up-to-date information on the disease's burden, given the present worldwide trend of increasing colorectal cancer incidence. Tumor recurrence and resistance are exacerbated by the presence of chemotherapy-resistant cancer stem cells that can generate rapidly proliferating tumor cells. In addition, tumor cells can evolve chemoresistance through adaptation mechanisms. In this work, we used in silico analysis to select suitable GEO datasets. In this study, we compared slow-growing cancer stem cells with high-growth colorectal cancer-derived cancer stem cells. We then evaluated the signal pathways, transcription factors, and kinases associated with these two types of cancer stem cells. A total of 980 upregulated genes and 870 downregulated genes were clustered. MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Fc gamma R-mediated phagocytosis, and Steroid biosynthesis signaling pathways were observed in upregulated genes. Also, caffeine metabolism, amino sugar and nucleotide sugar metabolism, TNF signaling pathway, and cytosolic DNA-sensing pathway were involved in downregulated genes. In the next step, we evaluated the best transcription factors and kinases in two types of cancer stem cells. In this regard, NR2F2, ZEB2, HEY1, and HDGF as transcription factors and PRDM5, SMAD, CBP, and KDM2B as critical kinases in upregulated genes. On the other hand, IRF1, SPDEF, NCOA1, and STAT1 transcription factors and CTNNB1 and CDH7 kinases were regulated low expression genes. Using bioinformatics analysis in the present study, we conducted an in-depth study of colorectal cancer stem cells at low and high growth rates so that we could take further steps to detect and even target these cells. Naturally, more additional tests are needed in this direction.

Keywords: colorectal cancer, bioinformatics analysis, transcription factor, kinases, cancer stem cells

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3876 Insulin-Producing Cells from Adult Human Bone Marrow Mesenchymal Stem Cells Control Chemically-Induced Diabetes in Dogs

Authors: Maha Azzam, Mahmoud Gabr, Mahmoud Zakaria, Ayman Refaie, Amani Ismail, Sherry Khater, Sylvia Ashamallah, Mohamed Ghoniem

Abstract:

Evidence was provided that human bone marrow-derived mesenhymal stem cells (HBM-MSCs) could be differentiated to form insulin-producing cells (IPCs). Transplantation of these cells was able to cure chemically-induced diabetes in nude mice. The efficacy of these cells to control diabetes in large animals was carried out to evaluate the sufficient number of cells needed/Kg body weight and to determine the functional longevity in vivo. Materials/Methods: Ten male mongrel dogs weighing 15-20 Kg were used in this study. Diabetes was chemically-induced in 7 dogs by a mixture of alloxan and streptozotocin. Three non-diabetic served as normal controls. Differentiated HBM-MSCs (5 million/Kg) were encapsulated in theracyte capsules and transplanted beneath the rectus sheath. Each dog received 2 capsules. One dog died 4 days postoperative from inhalation pneumonia. The remaining 6 dogs were followed up for 6-18 months. Results: Four dogs became normoglycemic within 6-8 weeks with normal glucose tolerance curves providing evidence that the transplanted cells were glucose-sensitive and insulin-responsive. In the remaining 2 dogs, fasting blood glucose was reduced but did not reach euglycemic levels. The sera of all transplanted dogs contained human insulin and c-peptide but negligible levels of canine insulin. When the HBM-MSCs loaded capsules were removed, rapid return of diabetic state was noted. The harvested capsules were examined by immunofluorescence. IPCs were seen and co-expression of with c-peptide was confirmed. Furthermore, all the pancreatic endocrine genes were expressed by the transplanted cells. Conclusions: This study provided evidence that theracyte capsules could protect the xenogenic HBM-MSCs from the host immune response. This is an important issue when clinical stem cell therapy is considered for definitive treatment for T1DM.

Keywords: diabetes, mesenchymal stem cells, dogs, Insulin-producing cells

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3875 Faculty Use of Geospatial Tools for Deep Learning in Science and Engineering Courses

Authors: Laura Rodriguez Amaya

Abstract:

Advances in science, technology, engineering, and mathematics (STEM) are viewed as important to countries’ national economies and their capacities to be competitive in the global economy. However, many countries experience low numbers of students entering these disciplines. To strengthen the professional STEM pipelines, it is important that students are retained in these disciplines at universities. Scholars agree that to retain students in universities’ STEM degrees, it is necessary that STEM course content shows the relevance of these academic fields to their daily lives. By increasing students’ understanding on the importance of these degrees and careers, students’ motivation to remain in these academic programs can also increase. An effective way to make STEM content relevant to students’ lives is the use of geospatial technologies and geovisualization in the classroom. The Geospatial Revolution, and the science and technology associated with it, has provided scientists and engineers with an incredible amount of data about Earth and Earth systems. This data can be used in the classroom to support instruction and make content relevant to all students. The purpose of this study was to find out the prevalence use of geospatial technologies and geovisualization as teaching practices in a USA university. The Teaching Practices Inventory survey, which is a modified version of the Carl Wieman Science Education Initiative Teaching Practices Inventory, was selected for the study. Faculty in the STEM disciplines that participated in a summer learning institute at a 4-year university in the USA constituted the population selected for the study. One of the summer learning institute’s main purpose was to have an impact on the teaching of STEM courses, particularly the teaching of gateway courses taken by many STEM majors. The sample population for the study is 97.5 of the total number of summer learning institute participants. Basic descriptive statistics through the Statistical Package for the Social Sciences (SPSS) were performed to find out: 1) The percentage of faculty using geospatial technologies and geovisualization; 2) Did the faculty associated department impact their use of geospatial tools?; and 3) Did the number of years in a teaching capacity impact their use of geospatial tools? Findings indicate that only 10 percent of respondents had used geospatial technologies, and 18 percent had used geospatial visualization. In addition, the use of geovisualization among faculty of different disciplines was broader than the use of geospatial technologies. The use of geospatial technologies concentrated in the engineering departments. Data seems to indicate the lack of incorporation of geospatial tools in STEM education. The use of geospatial tools is an effective way to engage students in deep STEM learning. Future research should look at the effect on student learning and retention in science and engineering programs when geospatial tools are used.

Keywords: engineering education, geospatial technology, geovisualization, STEM

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3874 Micromechanical Compatibility Between Cells and Scaffold Mediates the Efficacy of Regenerative Medicine

Authors: Li Yang, Yang Song, Martin Y. M. Chiang

Abstract:

Objective: To experimentally substantiate the micromechanical compatibility between cell and scaffold, in the regenerative medicine approach for restoring bone volume, is essential for phenotypic transitions Methods: Through nanotechnology and electrospinning process, nanofibrous scaffolds were fabricated to host dental follicle stem cells (DFSCs). Blends (50:50) of polycaprolactone (PCL) and silk fibroin (SF), mixed with various content of cellulose nanocrystals (CNC, up to 5% in weight), were electrospun to prepare nanofibrous scaffolds with heterogeneous microstructure in terms of fiber size. Colloidal probe atomic force microscopy (AFM) and conventional uniaxial tensile tests measured the scaffold stiffness at the micro-and macro-scale, respectively. The cell elastic modulus and cell-scaffold adhesive interaction (i.e., a chemical function) were examined through single-cell force spectroscopy using AFM. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine if the mechanotransduction signal (i.e., Yap1, Wwr2, Rac1, MAPK8, Ptk2 and Wnt5a) is upregulated by the scaffold stiffness at the micro-scale (cellular scale). Results: The presence of CNC produces fibrous scaffolds with a bimodal distribution of fiber diameter. This structural heterogeneity, which is CNC-composition dependent, remarkably modulates the mechanical functionality of scaffolds at microscale and macroscale simultaneously, but not the chemical functionality (i.e., only a single material property is varied). In in vitro tests, the osteogenic differentiation and gene expression associated with mechano-sensitive cell markers correlate to the degree of micromechanical compatibility between DFSCs and the scaffold. Conclusion: Cells require compliant scaffolds to encourage energetically favorable interactions for mechanotransduction, which are converted into changes in cellular biochemistry to direct the phenotypic evolution. The micromechanical compatibility is indeed important to the efficacy of regenerative medicine.

Keywords: phenotype transition, scaffold stiffness, electrospinning, cellulose nanocrystals, single-cell force spectroscopy

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3873 VR in the Middle School Classroom-An Experimental Study on Spatial Relations and Immersive Virtual Reality

Authors: Danielle Schneider, Ying Xie

Abstract:

Middle school science, technology, engineering, and math (STEM) teachers experience an exceptional challenge in the expectation to incorporate curricula that builds strong spatial reasoning skills on rudimentary geometry concepts. Because spatial ability is so closely tied to STEM students’ success, researchers are tasked to determine effective instructional practices that create an authentic learning environment within the immersive virtual reality learning environment (IVRLE). This study looked to investigate the effect of the IVRLE on middle school STEM students’ spatial reasoning skills as a methodology to benefit the STEM middle school students’ spatial reasoning skills. This experimental study was comprised of thirty 7th-grade STEM students divided into a treatment group that was engaged in an immersive VR platform where they engaged in building an object in the virtual realm by applying spatial processing and visualizing its dimensions and a control group that built the identical object using a desktop computer-based, computer-aided design (CAD) program. Before and after the students participated in the respective “3D modeling” environment, their spatial reasoning abilities were assessed using the Middle Grades Mathematics Project Spatial Visualization Test (MGMP-SVT). Additionally, both groups created a physical 3D model as a secondary measure to measure the effectiveness of the IVRLE. The results of a one-way ANOVA in this study identified a negative effect on those in the IVRLE. These findings suggest that with middle school students, virtual reality (VR) proved an inadequate tool to benefit spatial relation skills as compared to desktop-based CAD.

Keywords: virtual reality, spatial reasoning, CAD, middle school STEM

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3872 Influence of Preheating Self-Adhesive Cements on the Degree of Conversion, Cell Migration and Cell Viability in NIH/3T3

Authors: Celso Afonso Klein Jr., Henrique Cantarelli, Fernando Portella, Keiichi Hosaka, Eduardo Reston, Fabricio Collares, Roberto Zimmer

Abstract:

TTo evaluate the influence of preheating self-adhesive cement at 39ºC on cell migration, cytotoxicity and degree of conversion. RelyX U200, Set PP and MaxCem Elite were subjected to a degree of conversion analysis (FTIR-ATR). For the cytotoxicity analysis, extracts (24 h and 7 days) were placed in contact with NIH/3T3 cells. For cell migration, images were captured of each sample until the possible closure of the cleft occurred. In the results of the degree of conversion, preheating did not improve the conversion of cement. For the MTT, preheating did not improve the results within 24 hours. However, it generated positive results within 7 days for the Set PP resin cement. For cell migration, high rates of cell death were found in all groups. It is concluded that preheating at 39ºC caused a positive effect only in increasing the cell viability of the Set PP resin cement and that both materials analyzed are highly cytotoxic.

Keywords: dental cements, resin cements, degree of conversion, cytotoxicity, cell migration assays

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3871 Promoting Students' Worldview Through Integrative Education in the Process of Teaching Biology in Grades 11 and 12 of High School

Authors: Saule Shazhanbayeva, Denise van der Merwe

Abstract:

Study hypothesis: Nazarbayev Intellectual School of Kyzylorda’s Biology teachers can use STEM-integrated learning to improve students' problem-solving ability and responsibility as global citizens. The significance of this study is to indicate how the use of STEM integrative learning during Biology lessons could contribute to forming globally-minded students who are responsible community members. For the purposes of this study, worldview is defined as a view that is broader than the country of Kazakhstan, allowing students to see the significance of their scientific contributions to the world as global citizens. The context of worldview specifically indicates that most students have never traveled outside of their city or region within Kazakhstan. In order to broaden student understanding, it is imperative that students are exposed to different world views and contrasting ideas within the educational setting of Biology as the science being used for the research. This exposure promulgates students understanding of the significance they have as global citizens alongside the obligations which would rest on them as scientifically minded global citizens. Integrative learning should be Biological Science - with Technology and engineering in the form of problem-solving, and Mathematics to allow improved problem-solving skills to develop within the students of Nazarbayev Intellectual School (NIS) of Kyzylorda. The school's vision is to allow students to realise their role as global citizens and become responsible community members. STEM allows integrations by combining four subject skills to solve topical problems designed by educators. The methods used are based on qualitative analysis: for students’ performance during a problem-solution scenario; and Biology teacher interviews to ascertain their understanding of STEM implementation and willingness to integrate it into current lessons. The research indicated that NIS is ready for a shift into STEM lessons to promote globally responsible students. The only additional need is for proper STEM integrative lesson method training for teachers.

Keywords: global citizen, STEM, Biology, high-school

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3870 Rauvolfine B Isolated from the Bark of Rauvolfia reflexa (Apocynaceae) Induces Apoptosis through Activation of Caspase-9 Coupled with S Phase Cell Cycle Arrest

Authors: Mehran Fadaeinasab, Hamed Karimian, Najihah Mohd Hashim, Hapipah Mohd Ali

Abstract:

In this study, three indole alkaloids namely; rauvolfine B, macusine B, and isoreserpiline have been isolated from the dichloromethane crude extract of Rauvolfia reflexa bark (Apocynaceae). The structural elucidation of the isolated compounds has been performed using spectral methods such as UV, IR, MS, 1D, and 2D NMR. Rauvolfine B showed anti proliferation activity on HCT-116 cancer cell line, its cytotoxicity induction was observed using MTT assay in eight different cell lines. Annexin-V is serving as a marker for apoptotic cells and the Annexin-V-FITC assay was carried out to observe the detection of cell-surface Phosphatidylserine (PS). Apoptosis was confirmed by using caspase-8 and -9 assays. Cell cycle arrest was also investigated using flowcytometric analysis. rauvolfine B had exhibited significantly higher cytotoxicity against HCT-116 cell line. The treatment significantly arrested HCT-116 cells in the S phase. Together, the results presented in this study demonstrated that rauvolfine B inhibited the proliferation of HCT-116 cells and programmed cell death followed by cell cycle arrest.

Keywords: apocynacea, indole alkaloid, apoptosis, cell cycle arrest

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3869 Benign Osteoblastoma of the Mandible Resection and Replacement of the Defects with Decellularized Cattle Bone Scaffold with Mesenchymal Bone Marrow Stem Cells

Authors: K. Mardaleishvili, G. Loladze, G. Shatirishivili, D. Chakhunashvili, A. Vishnevskaya, Z. Kakabadze

Abstract:

Benign osteoblastoma is a benign tumor of the bone, usually affecting the vertebrae and long tubular bones. It is a rarely seen tumor of the facial bones. The authors present a case of a 28-year-old male patient with a tumor in mandibular body. The lesion was radically resected and histological analysis of the specimen demonstrated features typical of a benign osteoblastoma. The defect of the jaw was reconstructed with titanium implants and decellularized and lyophilized cattle bone matrix with mesenchymal bone marrow stem cells transplantation. This presentation describes the procedures for rehabilitating a patient with decellularized bone scaffold in the region of the face, recovering the facial contours and esthetics of the patient.

Keywords: facial bones, osteoblastoma, stem cells, transplantation

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3868 Regenerative Therapeutic Effect of Statin Nanoparticle-Loaded Adipose-Derived Stem Cells on Myocardial Infarction

Authors: Masaaki Ii, Takashi Saito, Yasuhiko Tabata, Shintaro Nemoto

Abstract:

Background: Clinical trials of autologous adipose-derived stem cell (AdSC) therapy for ischemic heart diseases (IHD) are now on-going. We have investigated the hypothesis that combination of AdSCs and statin, an agent with pleiotropic effects, could augment the therapeutic effect on myocardial infarction (MI). Methods and Results: Human AdSC functions with different doses of simvastatin-conjugated nanoparticle (STNP) uptake were evaluated by in vitro assays. STNP promoted the migration activity without changing the proliferation activity, and also up-regulated growth factors. Next, MI was induced by LAD ligation in nude mice, and the mice were assigned in the following groups 3 days after MI: 1) PBS (control), 2) NP-AdSCs (50000 cells), 3) STNP, and 4) STNP-AdSCs (50000 cells). Cardiac functional recovery assessed by echocardiography was improved at 4 weeks after surgery in STNP-AdSC group. Masson’s trichrome-stained sections revealed that LV fibrosis length was reduced, and the number of TUNEL-positive cardiomyocytes was less in STNP-AdSC group. Surprisingly, a number of de novo endogenous Nkx-2.5/GATA4 positive immature cardiomyocytes as well as massive vascular formation were observed in outer layer of infarcted myocardium despite of a few recruited/retained transfused STNP-AdSCs 4 weeks after MI in STNP-AdSC group. Finally, massive myocardial regeneration was observed 8 weeks after MI. Conclusions: Intravenously injected small number of statin nanoparticle-loaded hAdSCs exhibited a potent therapeutic effect inducing endogenous cardiac tissue regeneration.

Keywords: statin, drug delivery system, stem cells, cardiac regeneration

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3867 Variation in Wood Anatomical Properties of Acacia seyal var. seyal Tree Species Growing in Different Zones in Sudan

Authors: Hanadi Mohamed Shawgi Gamal, Ashraf Mohamed Ahmed Abdalla

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Sudan is endowed by a great diversity of tree species; nevertheless, the utilization of wood resources has traditionally concentrated on a few number of species. With the great variation in the climatic zones of Sudan, great variations are expected in the anatomical properties between and within species. This variation needs to be fully explored in order to suggest the best uses for the species. Modern research on wood has substantiated that the climatic condition where the species grow has significant effect on wood properties. Understanding the extent of variability of wood is important because the uses for each kind of wood are related to its characteristics; furthermore, the suitability or quality of wood for a particular purpose is determined by the variability of one or more of these characteristics. The present study demonstrates the effect of rainfall zones in some anatomical properties of Acacia seyal var. seyal growing in Sudan. For this purpose, twenty healthy trees were collected randomly from two zones (ten trees per zone). One zone with relatively low rainfall (273mm annually) which represented by North Kordofan state and White Nile state and the second with relatively high rainfall (701 mm annually) represented by Blue Nile state and South Kordofan state. From each sampled tree, a stem disc (3 cm thick) was cut at 10% from stem height. One radius was obtained in central stem dices. Two representative samples were taken from each disc, one at 10% distance from pith to bark, the second at 90% in order to represent the juvenile and mature wood. The investigated anatomical properties were fibers length, fibers and vessels diameter, lumen diameter, and wall thickness as well as cell proportions. The result of the current study reveals significant differences between zones in mature wood vessels diameter and wall thickness, as well as juvenile wood vessels, wall thickness. The higher values were detected in the drier zone. Significant differences were also observed in juvenile wood fiber length, diameter as well as wall thickness. Contrary to vessels diameter and wall thickness, the fiber length, diameter as well as wall thickness were decreased in the drier zone. No significant differences have been detected in cell proportions of juvenile and mature wood. The significant differences in some fiber and vessels dimension lead to expect significant differences in wood density. From these results, Acacia seyal var. seyal seems to be well adapted with the change in rainfall and may survive in any rainfall zone.

Keywords: Acacia seyal var. seyal, anatomical properties, rainfall zones, variation

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3866 On the Thermodynamics of Biological Cell Adhesion

Authors: Ben Nadler

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Cell adhesion plays a vital role in many cell activities. The motivation to model cell adhesion is to study important biological processes, such as cell spreading, cell aggregation, tissue formation, and cell adhesion, which are very challenging to study by experimental methods alone. This study provides important insight into cell adhesion, which can lead to improve regenerative medicine and tissue formation techniques. In this presentation the biological cells adhesion is mediated by receptors–ligands binding and the diffusivity of the receptor on the cell membrane surface. The ability of receptors to diffuse on the cell membrane surface yields a very unique and complicated adhesion mechanism, which is exclusive to cells. The phospholipid bilayer, which is the main component in the cell membrane, shows fluid-like behavior associated with the molecules’ diffusivity. The biological cell is modeled as a fluid-like membrane with negligible bending stiffness enclosing the cytoplasm fluid. The in-plane mechanical behavior of the cell membrane is assumed to depend only on the area change, which is motivated by the fluidity of the phospholipid bilayer. In addition, the presence of receptors influences on the local mechanical properties of the cell membrane is accounted for by including stress-free area change, which depends on the receptor density. Based on the physical properties of the receptors and ligands the attraction between the receptors and ligands is modeled as a charged-nonpolar which is a noncovalent interaction. Such interaction is a short-range type, which decays fast with distance. The mobility of the receptor on the cell membrane is modeled using the diffusion equation and Fick’s law is used to model the receptor–receptor interactions. The resultant interaction force, which includes receptor–ligand and receptor–receptor interaction, is decomposed into tangential part, which governs the receptor diffusion, and normal part, which governs the cell deformation and adhesion. The formulation of the governing equations and numerical simulations will be presented. Analysis of the adhesion characteristic and properties are discussed. The roles of various thermomechanical properties of the cell, receptors and ligands on the cell adhesion are investigated.

Keywords: cell adhesion, cell membrane, receptor-ligand interaction, receptor diffusion

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3865 Numerical Simulation of a Single Cell Passing through a Narrow Slit

Authors: Lanlan Xiao, Yang Liu, Shuo Chen, Bingmei Fu

Abstract:

Most cancer-related deaths are due to metastasis. Metastasis is a complex, multistep processes including the detachment of cancer cells from the primary tumor and the migration to distant targeted organs through blood and/or lymphatic circulations. During hematogenous metastasis, the emigration of tumor cells from the blood stream through the vascular wall into the tissue involves arrest in the microvasculature, adhesion to the endothelial cells forming the microvessel wall and transmigration to the tissue through the endothelial barrier termed as extravasation. The narrow slit between endothelial cells that line the microvessel wall is the principal pathway for tumor cell extravasation to the surrounding tissue. To understand this crucial step for tumor hematogenous metastasis, we used Dissipative Particle Dynamics method to investigate an individual cell passing through a narrow slit numerically. The cell membrane was simulated by a spring-based network model which can separate the internal cytoplasm and surrounding fluid. The effects of the cell elasticity, cell shape and cell surface area increase, and slit size on the cell transmigration through the slit were investigated. Under a fixed driven force, the cell with higher elasticity can be elongated more and pass faster through the slit. When the slit width decreases to 2/3 of the cell diameter, the spherical cell becomes jammed despite reducing its elasticity modulus by 10 times. However, transforming the cell from a spherical to ellipsoidal shape and increasing the cell surface area only by 3% can enable the cell to pass the narrow slit. Therefore the cell shape and surface area increase play a more important role than the cell elasticity in cell passing through the narrow slit. In addition, the simulation results indicate that the cell migration velocity decreases during entry but increases during exit of the slit, which is qualitatively in agreement with the experimental observation.

Keywords: dissipative particle dynamics, deformability, surface area increase, cell migration

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3864 Assessment of Barriers to the Clinical Adoption of Cell-Based Therapeutics

Authors: David Pettitt, Benjamin Davies, Georg Holländer, David Brindley

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Cellular based therapies, whose origins can be traced from the intertwined concepts of tissue engineering and regenerative medicine, have the potential to transform the current medical landscape and offer an approach to managing what were once considered untreatable diseases. However, despite a large increase in basic science activity in the cell therapy arena alongside a growing portfolio of cell therapy trials, the number of industry products available for widespread clinical use correlates poorly with such a magnitude of activity, with the number of cell-based therapeutics in mainstream use remaining comparatively low. This research serves to quantitatively assess the barriers to the clinical adoption of cell-based therapeutics through identification of unique barriers, specific challenges and opportunities facing the development and adoption of such therapies.

Keywords: cell therapy, clinical adoption, commercialization, translation

Procedia PDF Downloads 367