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    Isaac Liu

    Cell contraction force plays an important role in wound healing, inflammation,angiogenesis and metastasis. This study describes a novel method to quantify single cell contraction force in vitro using human aortic adventitial fibroblasts... more
    Cell contraction force plays an important role in wound healing, inflammation,angiogenesis and metastasis. This study describes a novel method to quantify single cell contraction force in vitro using human aortic adventitial fibroblasts embedded in a collagen gel. The technique is based on a depth sensing nano-indentation tester to measure the thickness and elasticity of collagen gels containing stimulated fibroblasts and a microscopy imaging system to estimate the gel area. In parallel, a simple theoretical model has been developed to calculate cell contraction force based on the measured parameters. Histamine (100 mM) was used to stimulate fibroblast contraction while the myosin light chain kinase inhibitor ML-7 (25 mM) was used to inhibit cell contraction. The collagen matrix used in the model provides a physiological environment for fibroblast contraction studies. Measurement of changes in collagen gel elasticity and thickness arising from histamine treatments provides a novel c...
    Rituximab is used with variable success in difficult FSGS. Because B cell depletion significantly affects T cell function, we characterized T cell subsets in patients with FSGS to determine if an immunologic signature predictive of... more
    Rituximab is used with variable success in difficult FSGS. Because B cell depletion significantly affects T cell function, we characterized T cell subsets in patients with FSGS to determine if an immunologic signature predictive of favorable response to rituximab could be identified. Twenty-two consecutive patients with FSGS (median age =14.4 years old; range =6.2-25.0 years old) and age of onset of nephrotic syndrome 1-18 years old receiving rituximab for clinical indications between October of 2009 and February of 2014 were studied. Indications for rituximab were lack of sustained remission despite calcineurin inhibitors (CNIs) and mycophenolate in steroid-resistant patients and lack of steroid-sparing effect with cyclophosphamide and CNI or CNI toxicity in steroid-dependent patients. Exclusion criteria were infantile onset, known genetic mutations, and secondary causes. Rituximab (375 mg/m(2)) was given fortnightly up to a maximum of four doses. Immunologic subset monitoring was ...
    ABSTRACT Epstein Barr virus;post-transplant lymphoproliferative disease;metachronous;cyclinE2;chronic active EBV infection
    While the appearance of red clots in the dialyzer is a common phenomenon in every hemodialysis unit, the occurrence of white thrombi in the tubing is relatively rare. We describe an adolescent male with recurrent white thrombi formation... more
    While the appearance of red clots in the dialyzer is a common phenomenon in every hemodialysis unit, the occurrence of white thrombi in the tubing is relatively rare. We describe an adolescent male with recurrent white thrombi formation in the hemodialysis tubing. This patient had chronic renal failure from focal segmental glomerulosclerosis, but was no longer nephrotic at the time of the thrombi formation. He had a history of recurrent thrombosis of his vascular access. However, no pro-thrombotic risk factors could be identified. White particulate matter, measuring 1 to 3mm in size, and adherent to the arterial and venous blood tubing lines was found during the rinse back of a hemodialysis session. This was associated with a 60% decrease in his platelet count. Light microscopic examination of the deposits revealed the presence of platelet aggregates. He subsequently developed thrombosis of his arteriovenous graft six hours later. The white thrombi recurred at the next dialysis sess...
    ABSTRACT We contend that repeatability of execution times is crucial to the validity of testing of real-time systems. However, computer architecture designs fail to deliver repeatable timing, a consequence of aggressive techniques that... more
    ABSTRACT We contend that repeatability of execution times is crucial to the validity of testing of real-time systems. However, computer architecture designs fail to deliver repeatable timing, a consequence of aggressive techniques that improve average-case performance. This paper introduces the Precision-Timed ARM (PTARM), a precision-timed (PRET) microarchitecture implementation that exhibits repeatable execution times without sacrificing performance. The PTARM employs a repeatable thread-interleaved pipeline with an exposed memory hierarchy, including a repeatable DRAM controller. Our benchmarks show an improved throughput compared to a single-threaded in-order five-stage pipeline, given sufficient parallelism in the software.
    Abstract—Many fuel systems for diesel engines are developed with the help of commercial one-dimensional computational fluid dynamics (1D CFD) solvers that model and simulate the behavior of fluid flow through the interconnected pipes... more
    Abstract—Many fuel systems for diesel engines are developed with the help of commercial one-dimensional computational fluid dynamics (1D CFD) solvers that model and simulate the behavior of fluid flow through the interconnected pipes off-line. This paper presents a ...
    ABSTRACT Many modern engine systems are designed using one-dimensional computational fluid dynamics (1D CFD). This same technique can be used to model these systems in real time. This real-time model can be used to create virtual sensors... more
    ABSTRACT Many modern engine systems are designed using one-dimensional computational fluid dynamics (1D CFD). This same technique can be used to model these systems in real time. This real-time model can be used to create virtual sensors in places where due to environmental or cost reasons physical sensors would not be practical. Achieving real-time performance of the CFD model requires more throughput than is available on single processor systems, so an Field Programmable Gate Array (FPGA) is employed. By employing an FPGA, we can synthesize and reconfigure our system to ensure determinism and lower resource usage. We instantiate several dedicated processing cores for parallel processing of sub-volumes. The number of cores can be configured to support up to 500 fluid volumes, more than enough for common 1D CFD models used in engines. This paper evaluates the feasibility of such a system and evaluates the complexity of such models against the GT-SUITE simulation software.
    Initiating continuous renal replacement therapy (CRRT) in infants exposes them to the dual hemodynamic challenges of high circuit extracorporeal volumes and potential membrane reactions, in the case of acrylonitrile AN69 membranes. The... more
    Initiating continuous renal replacement therapy (CRRT) in infants exposes them to the dual hemodynamic challenges of high circuit extracorporeal volumes and potential membrane reactions, in the case of acrylonitrile AN69 membranes. The use of the new Prismaflex HF20 membrane in hemodynamically unstable low-body-weight infants on inotropic support has not been reported. We describe the use of the HF20 (Gambro Lundia AB, Lund, Sweden) membrane in four low-body-weight infants (2.3 to 5.4 kg) with multi-organ dysfunction syndrome who were critically ill in the Pediatric Intensive Care Unit (PICU), hemodynamically unstable, and on inotropes. We were able to achieve target volume loss in all infants without compromising their hemodynamic status. Mean arterial pressures were maintained between 39 and 57 mmHg. The relatively low circuit volume of the HF20 set (60 ml) obviated the need for blood prime in the majority; however, when blood prime was required, there was no adverse reaction with the polyarylethersulfone (PAES) membrane. Solute clearance in these small infants was efficient with correction of metabolic acidosis and electrolyte abnormalities. Excellent circuit lifespan (56.3 ± 32.3 h) was observed. CRRT using the HF20 membrane is safe and hemodynamically well tolerated in high-risk, unstable low-body-weight infants with cardiac dysfunction on multiple inotropes.
    Side-channel attacks exploit information-leaky implementations of cryptographic algorithms to find the encryption key. These information leaks are caused by the underlying execution platform which contain hardware elements designed to... more
    Side-channel attacks exploit information-leaky implementations of cryptographic algorithms to find the encryption key. These information leaks are caused by the underlying execution platform which contain hardware elements designed to optimize performance at ...
    With multi-core and many-core architectures becoming the current focus of research and development, and as vast varieties of architectures and programming models emerging in research, the design space for applications is becoming... more
    With multi-core and many-core architectures becoming the current focus of research and development, and as vast varieties of architectures and programming models emerging in research, the design space for applications is becoming enormous. From the number of ...
    INTRODUCTION: Norovirus gastrointestinal disease (GID) outbreaks occur frequently in closed settings, with high attack rates. On October 16, 2008, a norovirus GID outbreak occurred at a Singapore military camp. This study describes the... more
    INTRODUCTION: Norovirus gastrointestinal disease (GID) outbreaks occur frequently in closed settings, with high attack rates. On October 16, 2008, a norovirus GID outbreak occurred at a Singapore military camp. This study describes the epidemiological investigations conducted to determine the cause of outbreak and the efficacy of the public health measures implemented.METHODS: Epidemiologic investigations included a case-control study of exposure to different food items and an environmental exposure survey. Stool samplings of patients and food handlers for common pathogens, and microbiologic testing of food and water samples were performed. Inspection of dining facilities and health screening of all food-handlers were also conducted.RESULTS: A total of 156 GID cases were reported on October 15-31, 2008. 24 (15.4%) personnel were positive for norovirus. The predominant symptoms were diarrhoea (76.3%) and abdominal pain (69.2%). There was no clinical correlation between any food item and the affected personnel. Testing of food and water samples, dining facility inspections and health screening of food handlers showed satisfactory results. The environmental exposure survey indicated possible transmission due to environmental contamination by vomitus in common areas. Comprehensive environmental decontamination was performed with hypochlorite solution, and personal hygiene measures were enforced. The outbreak lasted 17 days, with a decline in cases post intervention.CONCLUSION: Timely notification and prompt response can curtail disease transmission. Swift implementation of public health measures, such as emphasis on personal hygiene, isolation of affected cases and comprehensive disinfection of the environment, effectively stopped norovirus transmission and may be adapted for future GID outbreaks.
    Norovirus gastrointestinal disease (GID) outbreaks occur frequently in closed settings, with high attack rates. On October 16, 2008, a norovirus GID outbreak occurred at a Singapore military camp. This study describes the epidemiological... more
    Norovirus gastrointestinal disease (GID) outbreaks occur frequently in closed settings, with high attack rates. On October 16, 2008, a norovirus GID outbreak occurred at a Singapore military camp. This study describes the epidemiological investigations conducted to determine the cause of outbreak and the efficacy of the public health measures implemented. Epidemiologic investigations included a case-control study of exposure to different food items and an environmental exposure survey. Stool samplings of patients and food handlers for common pathogens, and microbiologic testing of food and water samples were performed. Inspection of dining facilities and health screening of all food-handlers were also conducted. A total of 156 GID cases were reported on October 15-31, 2008. 24 (15.4%) personnel were positive for norovirus. The predominant symptoms were diarrhoea (76.3%) and abdominal pain (69.2%). There was no clinical correlation between any food item and the affected personnel. Te...
    Tarek Abdelzaher Nevine Aboughazaleh Niwaer Ai Isaac Amundson Madhukar Anand Jim Anderson Björn Andersson Josef Angermeier Federico Angiolini Yanwar Asrigo David Atienza Neil Audsley Louise Avila Hakan Aydin Sanjoy Baruah Iain Bate... more
    Tarek Abdelzaher Nevine Aboughazaleh Niwaer Ai Isaac Amundson Madhukar Anand Jim Anderson Björn Andersson Josef Angermeier Federico Angiolini Yanwar Asrigo David Atienza Neil Audsley Louise Avila Hakan Aydin Sanjoy Baruah Iain Bate Guillem Bernat Luciano Bertini Gaurav Bhatia Tim Bissont Konstantinos Bletsas Aaron Block Alex Boettcher Alexander Boettcher Menouer Boubekeur Bjoern Brandenburg Philip Brik Bach Duy Bui Alan Burns Marco Caccamo John Calandrino Paul Caspi Samarjit Chakraborty Che-Wei Chang Yuan-Hao Chang Jie Chen Albert Cheng
    Nowadays, experimental biology gathers a large number of molecular and genetic data to understand the processes in living systems. Many of these data are evaluated on the level of cells, resulting in a changed phenotype of cells. Tools... more
    Nowadays, experimental biology gathers a large number of molecular and genetic data to understand the processes in living systems. Many of these data are evaluated on the level of cells, resulting in a changed phenotype of cells. Tools are required to translate the information on the cellular scale to the whole tissue, where multiple interacting cell types are involved. A recently developed multiscale three-dimensional 3-D simulation framework is designed for tissues in a flow equilibrium of highspeed migrating cells, as found frequently in immunological tissue. Cells can enter and leave the tissue according to some dynamics imposed by the considered biological system. The core component is an agent-based simulation of single cells that is build on top of a Delaunay triangulation. Reminiscent of molecular dynamics, the simulation tool is called Delaunay object dynamics (DOD). The DOD framework is applied to immunological tissue. In particular, the compartmental homeostasis of B lymphocytes and T lymphocytes in secondary lymphoid tissue is investigated on the basis of DOD simulations. This paper clearly demonstrates that the DOD method has the potential to 1) link different length scales between the molecular and the tissue level, 2) be a quantitative method in the sense that each parameter of the model corresponds to a measurable quantity, and 3) exhibit predictive power for novel conclusive experiments. The method can help to understand how global properties of a given biological system emerge from (complex) local interactions. This can help to design and guide experiments to test mechanisms that are identified by theoretical considerations of biological systems. We claim that the DOD architecture is suitable to investigate complex interactions of biological systems with large numbers of highly motile cells or more generally of discrete objects in space.