The non-receptor protein tyrosine phosphatase (PTP) SHP2 is an important component of RTK signali... more The non-receptor protein tyrosine phosphatase (PTP) SHP2 is an important component of RTK signaling in response to growth factor stimulus and sits just upstream of the RAS-MAPK signaling cascade. The first oncogenic phosphatase to be identified, SHP2 is dysregulated in multiple human diseases including the developmental disorders Noonan and Leopard syndromes, as well as leukemia, lung cancer and neuroblastoma where aberrant activity of SHP2 leads to uncontrolled MAPK signaling. Cancer-associated activating mutations in SHP2 impart an “auto-on” state of the enzyme, boosting basal activity by shifting the equilibrium away from the auto-inhibited state. Reduction of SHP2 activity through genetic knockdown suppresses tumor growth, validating SHP2 as a target for cancer therapy. SHP099, a recently reported potent and selective allosteric inhibitor of SHP2, stabilizes the auto-inhibited form of SHP2 through interactions with the N-terminal SH2 and C-terminal PTP domains of the protein. SH...
SHP2 is a nonreceptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene involved in c... more SHP2 is a nonreceptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also purportedly plays an important role in the programed cell death pathway (PD-1/PD-L1). As an oncoprotein associated with multiple cancer-related diseases, as well as a potential immunomodulator, controlling SHP2 activity is of significant therapeutic interest. Recently in our labs, a small molecule inhibitor of SHP2 was identified as an allosteric modulator that stabilizes the auto-inhibited conformation of SHP2. A high throughput screen was performed to identify progressable chemical matter and X-ray crystallography revealed the location of binding in a previously undisclosed allosteric binding pocket. Structure-based drug design was employed to optimize for SHP2 inhibition and several new protein-ligand interactions were characterized. These studies culminated in the discovery of 6-(4-amino-4-methylpiperidin-1-yl)-...
... a probabilistic framework In this approach, the isolated system performance is categorized ..... more ... a probabilistic framework In this approach, the isolated system performance is categorized ... Billinton, R, Allan RN, Reliability Evaluation of Power Systems, Plenum press, New York ... Billinton, R., Fotuhi-Firuzabad, M., "Reserve Capacity Assessment in Small Isolated Electric Power ...
The determination of how much generating capacity is required in an electric power system is a ba... more The determination of how much generating capacity is required in an electric power system is a basic element in power system planning. A second and equally important aspect of the planning process is the development of a suitable transmission system to move the generated energy to the major load points. Adequacy evaluation of composite generation and transmission systems is a complex task that includes detailed modeling of the generation and transmission facilities. The emergence of wind generation as an important electrical energy source creates some challenging complications in evaluating the adequacy of composite systems, as wind power behaves quite differently than conventional electric power generating facilities. This chapter discusses the general area of composite system adequacy evaluation and some of the various techniques that can be utilized to incorporate wind power in a system assessment. Wind power modeling in both generation and composite system adequacy evaluation is discussed and illustrated by application to two well-known reliability test systems. The studies presented utilize sequential and non-sequential Monte Carlo simulation and illustrate the addition of independent and correlated wind generation to the two test systems.
IET Generation, Transmission & Distribution, 2016
Variability of wind power is one of the main concerns of power system operation with significant ... more Variability of wind power is one of the main concerns of power system operation with significant wind power. Energy storage can be employed in conjunction with wind power to reduce the uncertainty associated with wind power. This study assumes the storage facility being operated by the wind farm operator for the explicit purpose of minimising the risk of wind power commitment. A time-dependent wind power model is developed in conjunction with the energy storage model for short operating lead times that are conditional on the initial wind and storage conditions. This study presents a probabilistic method to assess the reliability contribution of energy storage using two probabilistic indices: the wind power commitment risk and the unit commitment risk.
2009 IEEE Electrical Power & Energy Conference (EPEC), 2009
Wind energy application in electric power systems continues to increase globally due to public en... more Wind energy application in electric power systems continues to increase globally due to public environmental concerns and growth of energy demand. Due to the uncertainty in power fluctuations from wind sources, the ability of a power system to absorb available wind energy and maintain the system reliability and stability is reduced as the wind penetration is increased. It therefore becomes
2009 IEEE Power & Energy Society General Meeting, 2009
The (n-1) reliability criterion is the mostly widely used adequacy criterion in conventional tran... more The (n-1) reliability criterion is the mostly widely used adequacy criterion in conventional transmission system planning. The rapid growth of wind power, and the need to deliver this intermittent source of power from a location with rich wind resources to the power grid has created new challenges to determine adequate and economic transmission facility. This paper presents a probabilistic method to illustrate that the (n-1) criterion is not suitable for wind power transmission planning. However, probabilistic techniques that require complex statistical tools and considerable amounts of data are not readily applied in practice. This paper presents a simplified wind speed model that can generate wind speed probability distributions for wind farm sites if their annual mean wind speed and standard deviation values are known. The developed wind speed model can be combined with the wind turbine generator characteristics to obtain a wind farm generation model that can be further modified to incorporate the effect of the transmission line on wind power delivery. The results of adequacy studies on test systems are presented. The presented methods and discussions should be useful to power system planners and policy makers.
ABSTRACT This paper illustrates the effects on the load point and system reliability indices of a... more ABSTRACT This paper illustrates the effects on the load point and system reliability indices of a composite generation and transmission system of adding wind energy facilities with different degrees of wind speed correlation. The studies were conducted on the two test systems using a state sampling Monte Carlo approach. The analyses show the impacts of adding wind generating capacity at various locations in the two test systems and the effects on the load point and system indices of varying the wind penetration and the wind speed correlation levels. The studies presented illustrate the importance of considering wind speed correlation in the reliability assessment of composite generation and transmission systems containing large scale wind energy facilities.
The non-receptor protein tyrosine phosphatase (PTP) SHP2 is an important component of RTK signali... more The non-receptor protein tyrosine phosphatase (PTP) SHP2 is an important component of RTK signaling in response to growth factor stimulus and sits just upstream of the RAS-MAPK signaling cascade. The first oncogenic phosphatase to be identified, SHP2 is dysregulated in multiple human diseases including the developmental disorders Noonan and Leopard syndromes, as well as leukemia, lung cancer and neuroblastoma where aberrant activity of SHP2 leads to uncontrolled MAPK signaling. Cancer-associated activating mutations in SHP2 impart an “auto-on” state of the enzyme, boosting basal activity by shifting the equilibrium away from the auto-inhibited state. Reduction of SHP2 activity through genetic knockdown suppresses tumor growth, validating SHP2 as a target for cancer therapy. SHP099, a recently reported potent and selective allosteric inhibitor of SHP2, stabilizes the auto-inhibited form of SHP2 through interactions with the N-terminal SH2 and C-terminal PTP domains of the protein. SH...
SHP2 is a nonreceptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene involved in c... more SHP2 is a nonreceptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also purportedly plays an important role in the programed cell death pathway (PD-1/PD-L1). As an oncoprotein associated with multiple cancer-related diseases, as well as a potential immunomodulator, controlling SHP2 activity is of significant therapeutic interest. Recently in our labs, a small molecule inhibitor of SHP2 was identified as an allosteric modulator that stabilizes the auto-inhibited conformation of SHP2. A high throughput screen was performed to identify progressable chemical matter and X-ray crystallography revealed the location of binding in a previously undisclosed allosteric binding pocket. Structure-based drug design was employed to optimize for SHP2 inhibition and several new protein-ligand interactions were characterized. These studies culminated in the discovery of 6-(4-amino-4-methylpiperidin-1-yl)-...
... a probabilistic framework In this approach, the isolated system performance is categorized ..... more ... a probabilistic framework In this approach, the isolated system performance is categorized ... Billinton, R, Allan RN, Reliability Evaluation of Power Systems, Plenum press, New York ... Billinton, R., Fotuhi-Firuzabad, M., "Reserve Capacity Assessment in Small Isolated Electric Power ...
The determination of how much generating capacity is required in an electric power system is a ba... more The determination of how much generating capacity is required in an electric power system is a basic element in power system planning. A second and equally important aspect of the planning process is the development of a suitable transmission system to move the generated energy to the major load points. Adequacy evaluation of composite generation and transmission systems is a complex task that includes detailed modeling of the generation and transmission facilities. The emergence of wind generation as an important electrical energy source creates some challenging complications in evaluating the adequacy of composite systems, as wind power behaves quite differently than conventional electric power generating facilities. This chapter discusses the general area of composite system adequacy evaluation and some of the various techniques that can be utilized to incorporate wind power in a system assessment. Wind power modeling in both generation and composite system adequacy evaluation is discussed and illustrated by application to two well-known reliability test systems. The studies presented utilize sequential and non-sequential Monte Carlo simulation and illustrate the addition of independent and correlated wind generation to the two test systems.
IET Generation, Transmission & Distribution, 2016
Variability of wind power is one of the main concerns of power system operation with significant ... more Variability of wind power is one of the main concerns of power system operation with significant wind power. Energy storage can be employed in conjunction with wind power to reduce the uncertainty associated with wind power. This study assumes the storage facility being operated by the wind farm operator for the explicit purpose of minimising the risk of wind power commitment. A time-dependent wind power model is developed in conjunction with the energy storage model for short operating lead times that are conditional on the initial wind and storage conditions. This study presents a probabilistic method to assess the reliability contribution of energy storage using two probabilistic indices: the wind power commitment risk and the unit commitment risk.
2009 IEEE Electrical Power & Energy Conference (EPEC), 2009
Wind energy application in electric power systems continues to increase globally due to public en... more Wind energy application in electric power systems continues to increase globally due to public environmental concerns and growth of energy demand. Due to the uncertainty in power fluctuations from wind sources, the ability of a power system to absorb available wind energy and maintain the system reliability and stability is reduced as the wind penetration is increased. It therefore becomes
2009 IEEE Power & Energy Society General Meeting, 2009
The (n-1) reliability criterion is the mostly widely used adequacy criterion in conventional tran... more The (n-1) reliability criterion is the mostly widely used adequacy criterion in conventional transmission system planning. The rapid growth of wind power, and the need to deliver this intermittent source of power from a location with rich wind resources to the power grid has created new challenges to determine adequate and economic transmission facility. This paper presents a probabilistic method to illustrate that the (n-1) criterion is not suitable for wind power transmission planning. However, probabilistic techniques that require complex statistical tools and considerable amounts of data are not readily applied in practice. This paper presents a simplified wind speed model that can generate wind speed probability distributions for wind farm sites if their annual mean wind speed and standard deviation values are known. The developed wind speed model can be combined with the wind turbine generator characteristics to obtain a wind farm generation model that can be further modified to incorporate the effect of the transmission line on wind power delivery. The results of adequacy studies on test systems are presented. The presented methods and discussions should be useful to power system planners and policy makers.
ABSTRACT This paper illustrates the effects on the load point and system reliability indices of a... more ABSTRACT This paper illustrates the effects on the load point and system reliability indices of a composite generation and transmission system of adding wind energy facilities with different degrees of wind speed correlation. The studies were conducted on the two test systems using a state sampling Monte Carlo approach. The analyses show the impacts of adding wind generating capacity at various locations in the two test systems and the effects on the load point and system indices of varying the wind penetration and the wind speed correlation levels. The studies presented illustrate the importance of considering wind speed correlation in the reliability assessment of composite generation and transmission systems containing large scale wind energy facilities.
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Papers by Rajesh Karki