Biomedical subjects

Ken Lo

Publications and source records attributed to Ken Lo.

4 recordsLinked to original sources

PubMed2006

Global temperature change.

Global surface temperature has increased approximately 0.2 degrees C per decade in the past 30 years, similar to the warming rate predicted in the 1980s in initial global climate model simulations with transient greenhouse gas changes. Warming is larger in the Western Equatorial Pacific than in the Eastern Equatorial Pacific over the past century, and we suggest that the increased West-East temperature gradient may have increased the likelihood of strong El Niños, such as those of 1983 and 1998. Comparison of measured sea surface temperatures in the Western Pacific with paleoclimate data suggests that this critical ocean region, and probably the planet as a whole, is approximately as warm now as at the Holocene maximum and within approximately 1 degrees C of the maximum temperature of the past million years. We conclude that global warming of more than approximately 1 degrees C, relative to 2000, will constitute "dangerous" climate change as judged from likely effects on sea level and extermination of species.

Greenhouse Effect↗

PubMed2005

Earth's energy imbalance: confirmation and implications.

Our climate model, driven mainly by increasing human-made greenhouse gases and aerosols, among other forcings, calculates that Earth is now absorbing 0.85 +/- 0.15 watts per square meter more energy from the Sun than it is emitting to space. This imbalance is confirmed by precise measurements of increasing ocean heat content over the past 10 years. Implications include (i) the expectation of additional global warming of about 0.6 degrees C without further change of atmospheric composition; (ii) the confirmation of the climate system's lag in responding to forcings, implying the need for anticipatory actions to avoid any specified level of climate change; and (iii) the likelihood of acceleration of ice sheet disintegration and sea level rise.

Journal Article↗

PubMed2005

Stochastic modeling of blood coagulation initiation.

A kinetic Monte Carlo simulation was developed using the deterministic reaction network developed by the Mann laboratory for tissue-factor (TF)-initiated blood coagulation. The model predicted thrombin dynamics in recalcified whole blood (3-fold diluted) pretreated with convulxin (platelet GPVI activator) and picomolar levels of TF (0-14 pM). The model did not accurately predict coagulation times at low TF (0-0.7 pM). The simulation revealed that approximately 0.2 pM TF was the critical concentration to cause 50% of reactions containing 3-fold diluted whole blood to reach a clotting threshold of 0.05 U/ml thrombin by 1 h. Simulations of 1 nl of blood (5 pM TF) revealed small stochastic variations in thrombin initiation time, while 16.6 pl simulations were highly stochastic at this level of TF (50 molecules/16.6 pl). Further experiment and simulation will require evaluation of mechanisms of coagulation kinetics at subpicomolar levels of TF.

Automation↗

PubMed2004

Blood coagulation kinetics: high throughput method for real-time reaction monitoring.

A high throughput 384-well plate assay of blood function in 60 microl reactions with the fluorogenic thrombin substrate, boc-VPR-MCA, allowed for real-time monitoring of coagulation under a diverse set of reaction conditions. Using recalcified, citrated whole blood diluted 3-fold with corn trypsin inhibitor (to block Factor XIIa), addition of 0 to 13.8 pM of tissue factor (TF) reduced the time of maximal rate of thrombin production T(max) from 45 min to 11 min. Over this range of TF,T(max) was reduced from 35 min to 6 min by co-addition of 10 nM convulxin to activate platelets via GPVI. The maximal rate of thrombin production at T(max) was not a function of exogenously-added TF,Va, or reVIIa, but increased 30% with added convulxin. Addition of 0.07 to 0.7 pM TF along with convulxin produced small, but detectable reductions in T(max). Addition of up to 0.67 nM reVIIa reduced T(max) by up to 53% in the range of 0.7 to 7 pM TF. Interestingly, platelet factor 4 (2.7 microM) caused a prolongation of T(max) from 45 min to 78 min at 0 TF, while protamine (1.8 microM) reduced T(max) to 30 min at 0 TF. Finally, combinatorial reaction studies with exogenously-added ADP, histamine, fMLP, indomethacin, anti-CD18, and fibrinogen revealed no unusual synergies amongst the agents, but demonstrated a striking procoagulant activity of added fibrinogen, due to protease contaminants in the "purified" fibrinogen. This high throughput approach allowed automated profiling of blood (50 reactions/ml of blood) to generate large data sets for testing cellular-proteomic kinetic models, screening drug interactions, and potentially monitoring subtle changes in the functional phenotype of a patient blood sample.

Automation↗