Yan Martel - Academia.edu (original) (raw)

Papers by Yan Martel

Research paper thumbnail of Inactivation of TIF1γ Cooperates with KrasG12D to Induce Cystic Tumors of the Pancreas

PLOS Genetics, 2009

Inactivation of the Transforming Growth Factor Beta (TGFb) tumor suppressor pathway contributes t... more Inactivation of the Transforming Growth Factor Beta (TGFb) tumor suppressor pathway contributes to the progression of Pancreatic Ductal AdenoCarcinoma (PDAC) since it is inactivated in virtually all cases of this malignancy. Genetic lesions inactivating this pathway contribute to pancreatic tumor progression in mouse models. Transcriptional Intermediary Factor 1 gamma (TIF1c) has recently been proposed to be involved in TGFb signaling, functioning as either a positive or negative regulator of the pathway. Here, we addressed the role of TIF1c in pancreatic carcinogenesis. Using conditional Tif1c knockout mice (Tif1c lox/lox ), we selectively abrogated Tif1c expression in the pancreas of Pdx1-Cre;Tif1c lox/lox mice. We also generated Pdx1-Cre;LSL-Kras G12D ;Tif1c lox/lox mice to address the effect of Tif1c loss-of-function in precancerous lesions induced by oncogenic Kras G12D . Finally, we analyzed TIF1c expression in human pancreatic tumors. In our mouse model, we showed that Tif1c was dispensable for normal pancreatic development but cooperated with Kras activation to induce pancreatic tumors reminiscent of human Intraductal Papillary Mucinous Neoplasms (IPMNs). Interestingly, these cystic lesions resemble those observed in Pdx1-Cre;LSL-Kras G12D ;Smad4 lox/lox mice described by others. However, distinctive characteristics, such as the systematic presence of endocrine pseudo-islets within the papillary projections, suggest that SMAD4 and TIF1c don't have strictly redundant functions. Finally, we report that TIF1c expression is markedly downregulated in human pancreatic tumors by quantitative RT-PCR and immunohistochemistry supporting the relevance of these findings to human malignancy. This study suggests that TIF1c is critical for tumor suppression in the pancreas, brings new insight into the genetics of pancreatic cancer, and constitutes a promising model to decipher the respective roles of SMAD4 and TIF1c in the multifaceted functions of TGFb in carcinogenesis and development.

Research paper thumbnail of Transcriptional analysis of intracytoplasmically stained, FACS-purified cells by high-throughput, quantitative nuclease protection

Nature Biotechnology, 2009

Analyzing specialized cells in heterogeneous tissues is crucial for understanding organ function ... more Analyzing specialized cells in heterogeneous tissues is crucial for understanding organ function in health and disease. Thus far, however, there has been no convenient method for studying gene expression in cells purified by fluorescence-activated cell sorting (FACS) using intracellular markers. Here we show that the quantitative nuclease protection assay (qNPA) enables transcriptional analysis of intracytoplasmically stained cells sorted by FACS. Applying the method to mouse pancreatic islet-cell subsets, we detected both expected and unknown lineage-specific gene expression patterns. Some beta cells from pregnant animals were found to express Mafb, previously observed only in immature beta cells during embryonic development. The four 'housekeeping' genes tested were expressed in purified islet-cell subpopulations with a notable variability, dependent on both cell lineage and developmental stage. Application of qNPA to intracellularly stained, FACS-sorted cells should be broadly applicable to the analysis of gene expression in subpopulations of any heterogeneous tissue, including tumors.

Research paper thumbnail of Fuzzy two-stage material procurement planning problem

Journal of Intelligent Manufacturing, 2011

Material procurement planning (MPP) deals with the problem that purchasing the right quantity of ... more Material procurement planning (MPP) deals with the problem that purchasing the right quantity of material from the right supplier at the right time, a purchaser can reduce the material procurement costs via a reasonable MPP model. In order to handle the MPP problem in a fuzzy environment, this paper presents a new class of two-stage fuzzy MPP models, in which the material demand, the spot market material unit price and the spot market material supply quantity are assumed to be fuzzy variables with known possibility distributions. In addition, the procurement decisions are divided into two groups. Some procurement decisions, called first-stage decisions, must be taken before knowing the the particular values taken by the fuzzy variables; while some other decisions, called second-stage decisions, can be taken after the realizations of the fuzzy variables are known. The objective of the proposed fuzzy MPP model is to minimize the expected material procurement costs over the two stages. On other hand, since the fuzzy material demand, the fuzzy spot market material unit price and the fuzzy spot market material supply quantity are usually continuous fuzzy variables with infinite supports, the proposed MPP model belongs to an infinite-dimensional optimization problem whose objective function cannot be computed exactly. To avoid this difficulty, we suggest an approximation approach (AA) to evaluating the objective function, and turn the original MPP model into an approximating finite-dimensional one. To show the credibility of the AA, the convergence about the objective function of the approximating MPP model to that of the original MPP one is discussed. Since the exact analytical expression for the objective function in the approximating fuzzy MPP model is unavailable, and the approximating MPP model is a mixed-integer program that is neither linear nor convex, the traditional optimization algorithms cannot be used to solve it. Therefore, we design an AA-based particle swarm optimization to solve the approximating two-stage fuzzy MPP model. Finally, we apply the two-stage MPP model to an actual fuel procurement problem, and demonstrate the effectiveness of the designed algorithm via numerical experiments.

Research paper thumbnail of IPsec/VPN security policy correctness and assurance

Journal of High Speed Networks, 2006

With IPSec/VPN policies being widely deployed, how to correctly specify and configure them is cri... more With IPSec/VPN policies being widely deployed, how to correctly specify and configure them is critical in enforcing security requirements. Under current practice, IPSec/VPN policies are usually specified manually by system administrators and thus prone to errors. However, dynamic aspects in the network may interfere with the existing policy set up and thus cause unexpected conflict. To deal with these problems, we formally define IPSec security requirements, policies, and their correctness criteria.

Research paper thumbnail of Inactivation of TIF1γ Cooperates with KrasG12D to Induce Cystic Tumors of the Pancreas

PLOS Genetics, 2009

Inactivation of the Transforming Growth Factor Beta (TGFb) tumor suppressor pathway contributes t... more Inactivation of the Transforming Growth Factor Beta (TGFb) tumor suppressor pathway contributes to the progression of Pancreatic Ductal AdenoCarcinoma (PDAC) since it is inactivated in virtually all cases of this malignancy. Genetic lesions inactivating this pathway contribute to pancreatic tumor progression in mouse models. Transcriptional Intermediary Factor 1 gamma (TIF1c) has recently been proposed to be involved in TGFb signaling, functioning as either a positive or negative regulator of the pathway. Here, we addressed the role of TIF1c in pancreatic carcinogenesis. Using conditional Tif1c knockout mice (Tif1c lox/lox ), we selectively abrogated Tif1c expression in the pancreas of Pdx1-Cre;Tif1c lox/lox mice. We also generated Pdx1-Cre;LSL-Kras G12D ;Tif1c lox/lox mice to address the effect of Tif1c loss-of-function in precancerous lesions induced by oncogenic Kras G12D . Finally, we analyzed TIF1c expression in human pancreatic tumors. In our mouse model, we showed that Tif1c was dispensable for normal pancreatic development but cooperated with Kras activation to induce pancreatic tumors reminiscent of human Intraductal Papillary Mucinous Neoplasms (IPMNs). Interestingly, these cystic lesions resemble those observed in Pdx1-Cre;LSL-Kras G12D ;Smad4 lox/lox mice described by others. However, distinctive characteristics, such as the systematic presence of endocrine pseudo-islets within the papillary projections, suggest that SMAD4 and TIF1c don't have strictly redundant functions. Finally, we report that TIF1c expression is markedly downregulated in human pancreatic tumors by quantitative RT-PCR and immunohistochemistry supporting the relevance of these findings to human malignancy. This study suggests that TIF1c is critical for tumor suppression in the pancreas, brings new insight into the genetics of pancreatic cancer, and constitutes a promising model to decipher the respective roles of SMAD4 and TIF1c in the multifaceted functions of TGFb in carcinogenesis and development.

Research paper thumbnail of Transcriptional analysis of intracytoplasmically stained, FACS-purified cells by high-throughput, quantitative nuclease protection

Nature Biotechnology, 2009

Analyzing specialized cells in heterogeneous tissues is crucial for understanding organ function ... more Analyzing specialized cells in heterogeneous tissues is crucial for understanding organ function in health and disease. Thus far, however, there has been no convenient method for studying gene expression in cells purified by fluorescence-activated cell sorting (FACS) using intracellular markers. Here we show that the quantitative nuclease protection assay (qNPA) enables transcriptional analysis of intracytoplasmically stained cells sorted by FACS. Applying the method to mouse pancreatic islet-cell subsets, we detected both expected and unknown lineage-specific gene expression patterns. Some beta cells from pregnant animals were found to express Mafb, previously observed only in immature beta cells during embryonic development. The four 'housekeeping' genes tested were expressed in purified islet-cell subpopulations with a notable variability, dependent on both cell lineage and developmental stage. Application of qNPA to intracellularly stained, FACS-sorted cells should be broadly applicable to the analysis of gene expression in subpopulations of any heterogeneous tissue, including tumors.

Research paper thumbnail of Fuzzy two-stage material procurement planning problem

Journal of Intelligent Manufacturing, 2011

Material procurement planning (MPP) deals with the problem that purchasing the right quantity of ... more Material procurement planning (MPP) deals with the problem that purchasing the right quantity of material from the right supplier at the right time, a purchaser can reduce the material procurement costs via a reasonable MPP model. In order to handle the MPP problem in a fuzzy environment, this paper presents a new class of two-stage fuzzy MPP models, in which the material demand, the spot market material unit price and the spot market material supply quantity are assumed to be fuzzy variables with known possibility distributions. In addition, the procurement decisions are divided into two groups. Some procurement decisions, called first-stage decisions, must be taken before knowing the the particular values taken by the fuzzy variables; while some other decisions, called second-stage decisions, can be taken after the realizations of the fuzzy variables are known. The objective of the proposed fuzzy MPP model is to minimize the expected material procurement costs over the two stages. On other hand, since the fuzzy material demand, the fuzzy spot market material unit price and the fuzzy spot market material supply quantity are usually continuous fuzzy variables with infinite supports, the proposed MPP model belongs to an infinite-dimensional optimization problem whose objective function cannot be computed exactly. To avoid this difficulty, we suggest an approximation approach (AA) to evaluating the objective function, and turn the original MPP model into an approximating finite-dimensional one. To show the credibility of the AA, the convergence about the objective function of the approximating MPP model to that of the original MPP one is discussed. Since the exact analytical expression for the objective function in the approximating fuzzy MPP model is unavailable, and the approximating MPP model is a mixed-integer program that is neither linear nor convex, the traditional optimization algorithms cannot be used to solve it. Therefore, we design an AA-based particle swarm optimization to solve the approximating two-stage fuzzy MPP model. Finally, we apply the two-stage MPP model to an actual fuel procurement problem, and demonstrate the effectiveness of the designed algorithm via numerical experiments.

Research paper thumbnail of IPsec/VPN security policy correctness and assurance

Journal of High Speed Networks, 2006

With IPSec/VPN policies being widely deployed, how to correctly specify and configure them is cri... more With IPSec/VPN policies being widely deployed, how to correctly specify and configure them is critical in enforcing security requirements. Under current practice, IPSec/VPN policies are usually specified manually by system administrators and thus prone to errors. However, dynamic aspects in the network may interfere with the existing policy set up and thus cause unexpected conflict. To deal with these problems, we formally define IPSec security requirements, policies, and their correctness criteria.