Ariel Cohen | Pontificia Universidad Católica Argentina (original) (raw)

Papers by Ariel Cohen

Research paper thumbnail of Dynamic proteomics in individual human cells uncovers widespread cell-cycle dependence of nuclear proteins

Nature Methods, 2006

We examined cell cycle-dependent changes in the proteome of human cells by systematically measuri... more We examined cell cycle-dependent changes in the proteome of human cells by systematically measuring protein dynamics in individual living cells. We used time-lapse microscopy to measure the dynamics of a random subset of 20 nuclear proteins, each tagged with yellow fluorescent protein (YFP) at its endogenous chromosomal location. We synchronized the cells in silico by aligning protein dynamics in each cell between consecutive divisions. We observed widespread (40%) cell-cycle dependence of nuclear protein levels and detected previously unknown cell cycle-dependent localization changes. This approach to dynamic proteomics can aid in discovery and accurate quantification of the extensive regulation of protein concentration and localization in individual living cells.

Research paper thumbnail of Variability and memory of protein levels in human cells

Nature, 2006

Protein expression is a stochastic process that leads to phenotypic variation among cells 1-6 . T... more Protein expression is a stochastic process that leads to phenotypic variation among cells 1-6 . The cell-cell distribution of protein levels in microorganisms has been well characterized 7-23 but little is known about such variability in human cells. Here, we studied the variability of protein levels in human cells, as well as the temporal dynamics of this variability, and addressed whether cells with higher than average protein levels eventually have lower than average levels, and if so, over what timescale does this mixing occur. We measured fluctuations over time in the levels of 20 endogenous proteins in living human cells, tagged by the gene for yellow fluorescent protein at their chromosomal loci 24 . We found variability with a standard deviation that ranged, for different proteins, from about 15% to 30% of the mean. Mixing between high and low levels occurred for all proteins, but the mixing time was longer than two cell generations (more than 40 h) for many proteins. We also tagged pairs of proteins with two colours, and found that the levels of proteins in the same biological pathway were far more correlated than those of proteins in different pathways. The persistent memory for protein levels that we found might underlie individuality in cell behaviour and could set a timescale needed for signals to affect fully every member of a cell population.

Research paper thumbnail of Is Dobutamine Stress Echocardiography Useful for Noninvasive Differentiation of Ischemic from Idiopathic Dilated Cardiomyopathy

Angiology, 1997

Dobutamine stress echocardiography was performed in 56 consecutive patients, mean age: sixty-two ... more Dobutamine stress echocardiography was performed in 56 consecutive patients, mean age: sixty-two +/- twelve years. Twenty-two patients had an idiopathic dilated cardiomyopathy (group 1) and 34 had angiographically proven ischemic dilated cardiomyopathy (group 2). Wall motion score index and left ventricular ejection fraction were determined at baseline, 5 micrograms/kg/min, peak, and ten minutes after stepwise dobutamine infusion. Worsening or no change in global wall motion score was observed in 9 group 2 patients (26%) and 1 group 1 patient (5%, P = .07). No significant difference was observed with regard to wall motion score index decrease between baseline and peak dose. Left ventricular ejection fraction increase during dobutamine infusion was comparable in both groups. Thus, an ischemic response was observed more often in the coronary artery disease group, yielding a good specificity and positive predictive value although sensitivity was low. However, left ventricular function improvement did not help to discriminate patients with or without significant CAD.

Research paper thumbnail of Atherosclerotic Disease of the Aortic Arch and the Risk of Ischemic Stroke

New England Journal of Medicine, 1994

Background Atherosclerotic disease of the aortic arch has been suspected to be a potential source... more Background Atherosclerotic disease of the aortic arch has been suspected to be a potential source of cerebral emboli. We conducted a study to quantify the risk of ischemic stroke associated with atherosclerotic disease of the aortic arch.

Research paper thumbnail of Significant Association of Atrial Vulnerability With Atrial Septal Abnormalities in Young Patients With Ischemic Stroke of Unknown Cause

Research paper thumbnail of A Programming Interface for Supporting IP Traffic Processing

There are many possible applications for network elements which support packet routing along with... more There are many possible applications for network elements which support packet routing along with programmable packet manipulation. The goal is to design a programmable network element which provides the right “building blocks” for programming a variety of applications while providing good performance and a powerful programming interface. We explore an approach where a “fast path” component called a dispatcher (implemented in an OS kernel or in hardware) performs common packet processing tasks on behalf of programs running on the network element. The goal of this approach is to perform the processing of most packets within the dispatcher, while sending only few packets to the programs. Currently, the dispatcher can perform network address translations, TCP sequence number adjustments, and TCP window size adjustments on behalf of the programs. Additional dispatcher functionality such as packet queueing and scheduling is planned. This paper focuses on the programming interface for the dispatcher.

Research paper thumbnail of On the Performance of TCP Splicing for URL-Aware Redirection

This paper describes the design, implementation and performance of a layer-7 switch which support... more This paper describes the design, implementation and performance of a layer-7 switch which supports URL-aware redirection of HTTP traffic. Currently, there are several vendors who are beginning to an-nounce the availability of such switches in the mar-ket, but little or no ...

Research paper thumbnail of Dynamic proteomics in individual human cells uncovers widespread cell-cycle dependence of nuclear proteins

Nature Methods, 2006

We examined cell cycle-dependent changes in the proteome of human cells by systematically measuri... more We examined cell cycle-dependent changes in the proteome of human cells by systematically measuring protein dynamics in individual living cells. We used time-lapse microscopy to measure the dynamics of a random subset of 20 nuclear proteins, each tagged with yellow fluorescent protein (YFP) at its endogenous chromosomal location. We synchronized the cells in silico by aligning protein dynamics in each cell between consecutive divisions. We observed widespread (40%) cell-cycle dependence of nuclear protein levels and detected previously unknown cell cycle-dependent localization changes. This approach to dynamic proteomics can aid in discovery and accurate quantification of the extensive regulation of protein concentration and localization in individual living cells.

Research paper thumbnail of Variability and memory of protein levels in human cells

Nature, 2006

Protein expression is a stochastic process that leads to phenotypic variation among cells 1-6 . T... more Protein expression is a stochastic process that leads to phenotypic variation among cells 1-6 . The cell-cell distribution of protein levels in microorganisms has been well characterized 7-23 but little is known about such variability in human cells. Here, we studied the variability of protein levels in human cells, as well as the temporal dynamics of this variability, and addressed whether cells with higher than average protein levels eventually have lower than average levels, and if so, over what timescale does this mixing occur. We measured fluctuations over time in the levels of 20 endogenous proteins in living human cells, tagged by the gene for yellow fluorescent protein at their chromosomal loci 24 . We found variability with a standard deviation that ranged, for different proteins, from about 15% to 30% of the mean. Mixing between high and low levels occurred for all proteins, but the mixing time was longer than two cell generations (more than 40 h) for many proteins. We also tagged pairs of proteins with two colours, and found that the levels of proteins in the same biological pathway were far more correlated than those of proteins in different pathways. The persistent memory for protein levels that we found might underlie individuality in cell behaviour and could set a timescale needed for signals to affect fully every member of a cell population.

Research paper thumbnail of Is Dobutamine Stress Echocardiography Useful for Noninvasive Differentiation of Ischemic from Idiopathic Dilated Cardiomyopathy

Angiology, 1997

Dobutamine stress echocardiography was performed in 56 consecutive patients, mean age: sixty-two ... more Dobutamine stress echocardiography was performed in 56 consecutive patients, mean age: sixty-two +/- twelve years. Twenty-two patients had an idiopathic dilated cardiomyopathy (group 1) and 34 had angiographically proven ischemic dilated cardiomyopathy (group 2). Wall motion score index and left ventricular ejection fraction were determined at baseline, 5 micrograms/kg/min, peak, and ten minutes after stepwise dobutamine infusion. Worsening or no change in global wall motion score was observed in 9 group 2 patients (26%) and 1 group 1 patient (5%, P = .07). No significant difference was observed with regard to wall motion score index decrease between baseline and peak dose. Left ventricular ejection fraction increase during dobutamine infusion was comparable in both groups. Thus, an ischemic response was observed more often in the coronary artery disease group, yielding a good specificity and positive predictive value although sensitivity was low. However, left ventricular function improvement did not help to discriminate patients with or without significant CAD.

Research paper thumbnail of Atherosclerotic Disease of the Aortic Arch and the Risk of Ischemic Stroke

New England Journal of Medicine, 1994

Background Atherosclerotic disease of the aortic arch has been suspected to be a potential source... more Background Atherosclerotic disease of the aortic arch has been suspected to be a potential source of cerebral emboli. We conducted a study to quantify the risk of ischemic stroke associated with atherosclerotic disease of the aortic arch.

Research paper thumbnail of Significant Association of Atrial Vulnerability With Atrial Septal Abnormalities in Young Patients With Ischemic Stroke of Unknown Cause

Research paper thumbnail of A Programming Interface for Supporting IP Traffic Processing

There are many possible applications for network elements which support packet routing along with... more There are many possible applications for network elements which support packet routing along with programmable packet manipulation. The goal is to design a programmable network element which provides the right “building blocks” for programming a variety of applications while providing good performance and a powerful programming interface. We explore an approach where a “fast path” component called a dispatcher (implemented in an OS kernel or in hardware) performs common packet processing tasks on behalf of programs running on the network element. The goal of this approach is to perform the processing of most packets within the dispatcher, while sending only few packets to the programs. Currently, the dispatcher can perform network address translations, TCP sequence number adjustments, and TCP window size adjustments on behalf of the programs. Additional dispatcher functionality such as packet queueing and scheduling is planned. This paper focuses on the programming interface for the dispatcher.

Research paper thumbnail of On the Performance of TCP Splicing for URL-Aware Redirection

This paper describes the design, implementation and performance of a layer-7 switch which support... more This paper describes the design, implementation and performance of a layer-7 switch which supports URL-aware redirection of HTTP traffic. Currently, there are several vendors who are beginning to an-nounce the availability of such switches in the mar-ket, but little or no ...