Bulletin of Computer Science and Electrical Engineering (BCSEE)
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Novel Gene-Modified Mesenchymal Stem Cell Therapy Reverses Impaired Wound Healing in Ischemic Limbs
No full textOBJECTIVEHere we report a new method to increase therapeutic potential of mesenchymal stem/stromal cells (MSCs) for ischemic wound healing. We tested biologic effects of MSCs modified with E-selectin, a cell-adhesion molecule capable of inducing post-natal neovascularization, on a translational murine model. SUMMARY BACKGROUND DATATissue loss significantly worsens the risk of extremity amputation for patients with chronic limb-threatening ischemia (CLTI). MSCs-based therapeutics hold major promise for wound healing and therapeutic angiogenesis, but unmodified MSCs demonstrate only modest benefits. METHODSBone marrow cells harvested from FVB/ROSA26SormTmG donor mice were transduced with E-selectin-GFP/AAV-DJ or GFP/AAV-DJ (control). Ischemic wounds were created via a 4 mm punch biopsy in the ipsilateral limb after femoral artery ligation in recipient FVB mice and subsequently injected with PBS or 1×10^6 donor MSCGFP or MSCE-selectin-GFP. Wound closure was monitored daily for 7 postoperative days (POD), and tissues were harvested for molecular and histological analysis and immunofluorescence. Whole-body DiI perfusion and confocal microscopy was utilized to evaluate wound angiogenesis. RESULTSUnmodified MSCs do not express E-selectin, and MSCE-selectin-GFP gain stronger MSC phenotype yet maintain trilineage differentiation and colony-forming capability. MSCE-selectin-GFP therapy accelerates wound healing compared to MSCGFP and PBS treatment. Engrafted MSCE-selectin-GFP manifest stronger survival and viability in wounds at POD 7. Ischemic wounds treated with MSCE-selectin-GFP exhibit more abundant collagen deposition, and enhanced angiogenic response. CONCLUSIONWe establish a novel method to potentiate regenerative and pro-angiogenic capability of MSCs by modification with E-selectin/AAV. This innovative therapy carries potential as a platform worthy of future clinical studies
Measurement of the production of charm jets tagged with D0 mesons in pp collisions at s = 5.02 and 13 TeV
No full textAbstractThe measurement of the production of charm jets, identified by the presence of a D0meson in the jet constituents, is presented in proton–proton collisions at centre-of-mass energies ofs= 5.02 and 13 TeV with the ALICE detector at the CERN LHC. The D0mesons were reconstructed from their hadronic decay D0→ K−π+and the respective charge conjugate. Jets were reconstructed from D0-meson candidates and charged particles using the anti-kTalgorithm, in the jet transverse momentum range 5< pT,chjet<50 GeV/c, pseudorapidity |ηjet|<0.9 −R, and with the jet resolution parametersR= 0.2,0.4,0.6. The distribution of the jet momentum fraction carried by a D0meson along the jet axisz‖chwas measured in the range 0.4<z‖ch<1.0 in four ranges of the jet transverse momentum. Comparisons of results for different collision energies and jet resolution parameters are also presented. The measurements are compared to predictions from Monte Carlo event generators based on leading-order and next-to-leading-order perturbative quantum chromodynamics calculations. A generally good description of the main features of the data is obtained in spite of a few discrepancies at lowpT,chjet. Measurements were also done forR= 0.3 ats= 5.02 and are shown along with their comparisons to theoretical predictions in an appendix to this paper
A genome-wide search for pleiotropy in more than 100,000 harmonized longitudinal cognitive domain scores
No full textTherapeutic Perspectives for Inflammation and Senescence in Osteoarthritis Using Mesenchymal Stem Cells, Mesenchymal Stem Cell-Derived Extracellular Vesicles and Senolytic Agents
No full textOsteoarthritis (OA) is the most common cause of disability worldwide among the elderly. Alarmingly, the incidence of OA in individuals less than 40 years of age is rising, likely due to the increase in obesity and post-traumatic osteoarthritis (PTOA). In recent years, due to a better understanding of the underlying pathophysiology of OA, several potential therapeutic approaches targeting specific molecular pathways have been identified. In particular, the role of inflammation and the immune system has been increasingly recognized as important in a variety of musculoskeletal diseases, including OA. Similarly, higher levels of host cellular senescence, characterized by cessation of cell division and the secretion of a senescence-associated secretory phenotype (SASP) within the local tissue microenvironments, have also been linked to OA and its progression. New advances in the field, including stem cell therapies and senolytics, are emerging with the goal of slowing disease progression. Mesenchymal stem/stromal cells (MSCs) are a subset of multipotent adult stem cells that have demonstrated the potential to modulate unchecked inflammation, reverse fibrosis, attenuate pain, and potentially treat patients with OA. Numerous studies have demonstrated the potential of MSC extracellular vesicles (EVs) as cell-free treatments that comply with FDA regulations. EVs, including exosomes and microvesicles, are released by numerous cell types and are increasingly recognized as playing a critical role in cell–cell communication in age-related diseases, including OA. Treatment strategies for OA are being developed that target senescent cells and the paracrine and autocrine secretions of SASP. This article highlights the encouraging potential for MSC or MSC-derived products alone or in combination with senolytics to control patient symptoms and potentially mitigate the progression of OA. We will also explore the application of genomic principles to the study of OA and the potential for the discovery of OA phenotypes that can motivate more precise patient-driven treatments
Gaussian processes at the Helm(holtz): A more fluid model for ocean currents
No full textOceanographers are interested in predicting ocean currents and identifying
divergences in a current vector field based on sparse observations of buoy
velocities. Since we expect current dynamics to be smooth but highly
non-linear, Gaussian processes (GPs) offer an attractive model. But we show
that applying a GP with a standard stationary kernel directly to buoy data can
struggle at both current prediction and divergence identification -- due to
some physically unrealistic prior assumptions. To better reflect known physical
properties of currents, we propose to instead put a standard stationary kernel
on the divergence and curl-free components of a vector field obtained through a
Helmholtz decomposition. We show that, because this decomposition relates to
the original vector field just via mixed partial derivatives, we can still
perform inference given the original data with only a small constant multiple
of additional computational expense. We illustrate the benefits of our method
on synthetic and real ocean data
Design of Short Circuit Indicator for Medium Voltage Systems
No full textA phenomenon known as a short circuit occurs when the input terminals of a power source come into direct electrical contact with one another, which results in a very high flow of current. This results in the production of a significant amount of heat, which poses a risk to the system itself and those located nearby. So, it is vital to identify a short circuit problem and rapidly respond to it once it is identified. When connected, the Short Circuit Indicator automatically detects a short circuit in a circuit to which it is attached. We were able to show the short circuit in our circuit board by inserting a piece of wire that has a resistance value that is very low, almost equal to zero, and which, as a result, created a short circuit at the source connection. Three single-phase currents imply high voltage power line short faults. Zero sequence currents imply grounding failure. Line patrollers may see or hear short circuits or grounding issues on 3kV-40.5kV power distribution networks, switchgear, cable branching units, etc. Answer "What is a short circuit?" to study them. It's how? What time? and why? Short-circuit prevention. Short circuit (fault current) studies must be done to ensure that electrical system equipment can tolerate short circuit energy. Grounding shipboard equipment is difficult. Grounding the power transformer's return to the chassis eliminates direct wiring. Power supply load connects to transformer return. Overcapacity may damage equipment and endanger lives. Short circuits triggered many fires. Short circuits safeguard structures
Efficient adsorption of aromatic and aliphatic hydrocarbons by electrospun hydrophobic PTFE-NiO composite nanofiber filter mats
No full textAromatic and aliphatic hydrocarbons (AAHs) are comprised of a variety of gaseous chemicals that may affect human and environmental health. To remove AAHs from air, polytetrafluoroethylene-nickel oxide (PTFE-NiO) composite nanofiber filter mats (NFMs) were synthesized and characterized for their ability to effectively adsorb AAHs. The NiO-nanoparticle-doped mats were fabricated by green electrospinning of PTFE and polyvinyl alcohol (PVA) mixtures added with nickel (II) nitrate hexahydrate in the spinning solution followed by surface heat treatment. FE-SEM FTIR, Raman spectroscopy, sessile drop and Jar methods were applied as characterization techniques. The diameter of the electrospun nanofibers without NiO dopant ranged from 0.34 ± 21.61 to 0.23 ± 10.12 µm, whereas a reduction in diameter of NiO-doped nanofibers was obtained, ranging between pristine to 0.25 ± 24.12 µm and 0.12 ± 85.75 µm with heat treatment. 6% (by weight) NiO-doped PTFE composite NFMs exhibited a high water-contact angle of 120 ± 2.20 degrees; the high hydrophobicity value aided self-cleansing property of NFMs for practical applications. UV adsorption capability for heat-treated PTFE-NiO NFMs was evaluated for three AAHs, and the results showed that 6 wt% NiO adsorbed 1.41, 0.67, and 0.73 µg/mg of toluene, formaldehyde and acetone, respectively. These findings reveal the potential applicability of the prepared filter mats for capturing various AAHs from polluted air
Quality by Design Bioprocess Development and Characterization For IDCT: An Allogeneic Cell Therapy for Lower Back Pain
No full textAllogeneic cell therapies provide a new tool to regrow, repair, or replace damaged tissues for large populations of patients by using cells derived from unrelated donor tissue. Lower back pain is the most prevalent cause of disability and is frequently characterized by the breakdown of intervertebral disc tissue, making it a prime candidate for regenerative cell therapy. Our team is developing an allogeneic progenitor cell therapy to treat painful disc degeneration called IDCT (rebonuputemcel). Unfortunately, regenerative cell therapies have seen limited commercial success due largely to unclear regulatory expectations, high levels of variation in product quality from unrelated donor tissue, and difficulties culturing therapeutic cells at a commercially viable scale. Quality by Design is an approach employed by the biopharmaceutical field to build quality into a product by first defining a quality target and then building biomanufacturing methods around the ability to match that quality target. Herein we discuss the primary challenges in the bioprocess development of IDCT using a Quality by Design approach. The first chapter introduces the challenges associated with identification and management of variability for cell therapies in a commercial context. The second explores the challenges, successes, and failures we had with transitioning our cell sphere process to a large-scale bioprocess modality. The third chapter shows our use of QbD and Design of Experiments to build a multi-dimensional process design space where the impact of media, donor, and process variability on our final quality target is quantified. In the final chapter, we significantly improve upon a linear regression-based process model using artificial neural networks. By exploring regulatory pathways, scale-up of cell spheres, media, process, and donor variability, as well as modeling and optimization approaches, we illustrate a practical approach to bioprocess development and characterization for a cell therapy product. </p
Effect of Perceived Social Support on the Relationship Between Psychological Distress and Family Satisfaction Among Family Members of Intensive Care Unit Patients
No full textAims: 1) To examine the relationship between psychological distress (perceived stress, anxiety, and depressive symptoms) and family satisfaction (overall satisfaction, satisfaction with care, and satisfaction with decision-making), 2) explore the relationship between psychological distress and perceived social support, and 3) explore the extent to which perceived social support moderates the relationship between psychological distress and family satisfaction.Methods: A cross-sectional study involving 63 family members of patients with at least 48 hours in the ICU was conducted. Questionnaires for perceived stress, anxiety symptoms, depressive symptoms, perceived social support, and family satisfaction were administered by phone, either in English or Spanish language: Data analysis included descriptive statistics, Mann-Whitney U tests, chi-square tests, Fisher’s Exact tests, and hierarchical regressions.Results: 27% presented clinically significant symptoms (CSS) of anxiety, 25.4% of depression, and 76.2% high perception of social support. Perceived stress was significantly associated with all family satisfaction domains. No significant differences in family satisfaction were found among family members with or without CSS of anxiety and depression. Family members with low/fair perceived social support reported significantly greater perceived stress. No significant associations were found between family members with or without CSS of anxiety or depression, and their level of perceived social support. No evidence of moderation of perceived social support on the relationship between psychological distress and family satisfaction was found. However, perceived social support significantly predicted overall satisfaction and satisfaction with care in several main effects models.Conclusions: Knowing the psychosocial status of ICU family members may assist in the identification and support of those at risk of low satisfaction. Future studies should delve into the role of perceived social support on family satisfaction. </p