8,792 research outputs found
Delay-rate tradeoff for ergodic interference alignment in the Gaussian case
In interference alignment, users sharing a wireless channel are each able to
achieve data rates of up to half of the non-interfering channel capacity, no
matter the number of users. In an ergodic setting, this is achieved by pairing
complementary channel realizations in order to amplify signals and cancel
interference. However, this scheme has the possibility for large delays in
decoding message symbols. We show that delay can be mitigated by using outputs
from potentially more than two channel realizations, although data rate may be
reduced. We further demonstrate the tradeoff between rate and delay via a
time-sharing strategy. Our analysis considers Gaussian channels; an extension
to finite field channels is also possible.Comment: 7 pages, 2 figures, presented at 48th Allerton Conference on
Communication Control and Computing, 2010. Includes appendix detailing Markov
chain analysi
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Patient and Disease-Specific Induced Pluripotent Stem Cells for Discovery of Personalized Cardiovascular Drugs and Therapeutics.
Human induced pluripotent stem cells (iPSCs) have emerged as an effective platform for regenerative therapy, disease modeling, and drug discovery. iPSCs allow for the production of limitless supply of patient-specific somatic cells that enable advancement in cardiovascular precision medicine. Over the past decade, researchers have developed protocols to differentiate iPSCs to multiple cardiovascular lineages, as well as to enhance the maturity and functionality of these cells. Despite significant advances, drug therapy and discovery for cardiovascular disease have lagged behind other fields such as oncology. We speculate that this paucity of drug discovery is due to a previous lack of efficient, reproducible, and translational model systems. Notably, existing drug discovery and testing platforms rely on animal studies and clinical trials, but investigations in animal models have inherent limitations due to interspecies differences. Moreover, clinical trials are inherently flawed by assuming that all individuals with a disease will respond identically to a therapy, ignoring the genetic and epigenomic variations that define our individuality. With ever-improving differentiation and phenotyping methods, patient-specific iPSC-derived cardiovascular cells allow unprecedented opportunities to discover new drug targets and screen compounds for cardiovascular disease. Imbued with the genetic information of an individual, iPSCs will vastly improve our ability to test drugs efficiently, as well as tailor and titrate drug therapy for each patient
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Wearable activity sensors and early pain after total joint arthroplasty.
A prospective observational cohort of 20 primary total hip arthroplasty (n = 12) and total knee arthroplasty (n = 8) patients (mean age: 63 ± 6 years) was passively monitored with a consumer-level wearable activity sensor before and 6 weeks after surgery. Patients were clustered by minimal change or decreased activity using sensor data. Decreased postoperative activity was associated with greater pain reduction (-5.5 vs -2.0, P = .03). All patients surpassed minimal clinical benefit thresholds of total joint arthroplasty (TJA) (Hip Disability and Osteoarthritis Score Junior 30.5 vs 20.8, P = .23; Knee Injury and Osteoarthritis Outcome Score Junior 23.3 vs 18.2, P = .77) within 6 weeks. Patients who objectively "take it easy" after TJA may experience less pain with no difference in early subjective outcome. Remote, passive analysis of outpatient wearable sensor data may permit real-time detection of early problems after TJA
Hemodynamic Forces Regulate Embryonic Stem Cell Commitment to Vascular Progenitors
Pluripotent embryonic stem can (ES) cells can differentiate into all cell lineages. During the process of embryonic development, ES cells are exposed to fluid flow or blood flow generated by the contracting heart. Absence of fluid flow results in the formation of abnormal cardiac chambers and valve formation. Thus, hemodynamic forces and ES cell differentiation to vascular progenitor cells (VPCs) are of emerging interests for restoring endothelial dysfunction, inducing angiogenesis, and forming blood vessel networks. Hemodynamic forces such as fluid shear stress increase the percentage of cells in the S and G2-M phases, and induce decondensation of chromatin for gene transcription. Fluid shear stress further accelerates ES commitment to CD31+ VPC vascular progenitor cells. These ES-derived CD31+ cells express endothelial nitric oxide synthase (eNOS) and von Willebrand factor (vWF). They are also capable of LDL uptake and tubular network formation. In this context, understanding hemodynamic forces and ES cell kinetics of differentiation towards endothelial lineage has potential therapeutic applications for repairing vascular damage and engineering vascular graft. Multidisciplinary team approach will likely garner momentum and synergize expertise to address the current road blocks in basic stem cell research for engraftable, restorative, low immunogenic, and non-tumorigenic endothelial progenitors in high purity and stability
An efficient surrogate model for emulation and physics extraction of large eddy simulations
In the quest for advanced propulsion and power-generation systems,
high-fidelity simulations are too computationally expensive to survey the
desired design space, and a new design methodology is needed that combines
engineering physics, computer simulations and statistical modeling. In this
paper, we propose a new surrogate model that provides efficient prediction and
uncertainty quantification of turbulent flows in swirl injectors with varying
geometries, devices commonly used in many engineering applications. The novelty
of the proposed method lies in the incorporation of known physical properties
of the fluid flow as {simplifying assumptions} for the statistical model. In
view of the massive simulation data at hand, which is on the order of hundreds
of gigabytes, these assumptions allow for accurate flow predictions in around
an hour of computation time. To contrast, existing flow emulators which forgo
such simplications may require more computation time for training and
prediction than is needed for conducting the simulation itself. Moreover, by
accounting for coupling mechanisms between flow variables, the proposed model
can jointly reduce prediction uncertainty and extract useful flow physics,
which can then be used to guide further investigations.Comment: Submitted to JASA A&C
Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas.
The use of cells derived from pluripotent stem cells (PSCs) for regenerative therapies confers a considerable risk for neoplastic growth and teratoma formation. Preclinical and clinical assessment of such therapies will require suitable monitoring strategies to understand and mitigate these risks. Here we generated human-induced pluripotent stem cells (iPSCs), selected clones that continued to express reprogramming factors after differentiation into cardiomyocytes, and transplanted these cardiomyocytes into immunocompromised rat hearts post-myocardial infarction. We compared magnetic resonance imaging (MRI), cardiac ultrasound, and serum biomarkers for their ability to delineate teratoma formation and growth. MRI enabled the detection of teratomas with a volume >8 mm(3). A combination of three plasma biomarkers (CEA, AFP, and HCG) was able to detect teratomas with a volume >17 mm(3) and with a sensitivity of more than 87%. Based on our findings, a combination of serum biomarkers with MRI screening may offer the highest sensitivity for teratoma detection and tracking
Cancer therapy-induced cardiomyopathy: can human induced pluripotent stem cell modelling help prevent it?
Cardiotoxic effects from cancer therapy are a major cause of morbidity during cancer treatment. Unexpected toxicity can occur during treatment and/or after completion of therapy, into the time of cancer survivorship. While older drugs such as anthracyclines have well-known cardiotoxic effects, newer drugs such as tyrosine kinase inhibitors, proteasome inhibitors, and immunotherapies also can cause diverse cardiovascular and metabolic complications. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly being used as instruments for disease modelling, drug discovery, and mechanistic toxicity studies. Promising results with hiPSC-CM chemotherapy studies are raising hopes for improving cancer therapies through personalized medicine and safer drug development. Here, we review the cardiotoxicity profiles of common chemotherapeutic agents as well as efforts to model them in vitro using hiPSC-CMs
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Big bottlenecks in cardiovascular tissue engineering.
Although tissue engineering using human-induced pluripotent stem cells is a promising approach for treatment of cardiovascular diseases, some limiting factors include the survival, electrical integration, maturity, scalability, and immune response of three-dimensional (3D) engineered tissues. Here we discuss these important roadblocks facing the tissue engineering field and suggest potential approaches to overcome these challenges
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