The epichaperome is a new cancer target composed of hyperconnected networks of chaperome members ... more The epichaperome is a new cancer target composed of hyperconnected networks of chaperome members that facilitate cell survival. Cancers with an altered chaperone configuration may be susceptible to epichaperome inhibitors. We developed a flow cytometry-based assay for evaluation and monitoring of epichaperome abundance at the single cell level, with the goal of prospectively identifying patients likely to respond to epichaperome inhibitors, to measure target engagement, and dependency during treatment. As proof of principle, we describe a patient with an unclassified myeloproliferative neoplasm harboring a novel PML-SYK fusion, who progressed to acute myeloid leukemia despite chemotherapy and allogeneic stem cell transplant. The leukemia was identified as having high epichaperome abundance. We obtained compassionate access to an investigational epichaperome inhibitor, PU-H71. After 16 doses, the patient achieved durable complete remission. These encouraging results suggest that furt...
Cancer is often associated with alterations in the chaperome, a collection of chaperones, cochape... more Cancer is often associated with alterations in the chaperome, a collection of chaperones, cochaperones, and other cofactors. Changes in the expression levels of components of the chaperome, in the interaction strength among chaperome components, alterations in chaperome constituency, and in the cellular location of chaperome members, are all hallmarks of cancer. Here we aim to provide an overview on how chemical biology has played a role in deciphering such complexity in the biology of the chaperome in cancer and in other diseases. The focus here is narrow and on pathologic changes in the chaperome executed by enhancing the interaction strength between components of distinct chaperome pathways, specifically between those of HSP90 and HSP70 pathways. We will review chemical tools and chemical probe-based assays, with a focus on HSP90. We will discuss how kinetic binding, not classical equilibrium binding, is most appropriate in the development of drugs and probes for the chaperome in disease. We will then present our view on how chaperome inhibitors may become potential drugs and diagnostics in cancer.
A copper-mediated synthesis of diaryl sulfides utilizing Cu(I)-thiophene-2-carboxylate (CuTC) is ... more A copper-mediated synthesis of diaryl sulfides utilizing Cu(I)-thiophene-2-carboxylate (CuTC) is described. We demonstrate the use of CuTC as a soluble, non-basic catalyst in the coupling of aryl iodides and aryl thiols in the synthesis of synthetically advanced diaryl sulfides. This method allows for the successful coupling of challenging substrates including -substituted and heteroaryl iodides and thiols. Additionally, most of the aryl iodide substrates used here contain the privileged piperazine scaffold bound to a pyrimidine, pyridine, or phenyl ring and thus this method allows for the elaboration of complex piperazine scaffolds into molecules of biological interest. The method described here enables the incorporation of late-stage structural diversity into diaryl sulfides containing the piperazine ring, thus enhancing the number and nature of derivatives available for SAR investigation.
In this Opinion article, we aim to address how cells adapt to stress and the repercussions chroni... more In this Opinion article, we aim to address how cells adapt to stress and the repercussions chronic stress has on cellular function. We consider acute and chronic stress-induced changes at the cellular level, with a focus on a regulator of cellular stress, the chaperome, which is a protein assembly that encompasses molecular chaperones, co-chaperones and other co-factors. We discuss how the chaperome takes on distinct functions under conditions of stress that are executed in ways that differ from the one-on-one cyclic, dynamic functions exhibited by distinct molecular chaperones. We argue that through the formation of multimeric stable chaperome complexes, a state of chaperome hyperconnectivity, or networking, is gained. The role of these chaperome networks is to act as multimolecular scaffolds, a particularly important function in cancer, where they increase the efficacy and functional diversity of several cellular processes. We predict that these concepts will change how we develop...
Stresses associated with disease may pathologically remodel the proteome by both increasing inter... more Stresses associated with disease may pathologically remodel the proteome by both increasing interaction strength and altering interaction partners, resulting in proteome-wide connectivity dysfunctions. Chaperones play an important role in these alterations, but how these changes are executed remains largely unknown. Our study unveils a specific N-glycosylation pattern used by a chaperone, Glucose-regulated protein 94 (GRP94), to alter its conformational fitness and stabilize a state most permissive for stable interactions with proteins at the plasma membrane. This "protein assembly mutation' remodels protein networks and properties of the cell. We show in cells, human specimens, and mouse xenografts that proteome connectivity is restorable by inhibition of the Nglycosylated GRP94 variant. In summary, we provide biochemical evidence for stressor-induced chaperone-mediated protein mis-assemblies and demonstrate how these alterations are actionable in disease.
Deep Reinforcement Learning methods have achieved state of the art performance in learning contro... more Deep Reinforcement Learning methods have achieved state of the art performance in learning control policies for the games in the Atari 2600 domain. One of the important parameters in the Arcade Learning Environment (ALE, [Bellemare et al., 2013]) is the frame skip rate. It decides the granularity at which agents can control game play. A frame skip value of k allows the agent to repeat a selected action k number of times. The current state of the art architectures like Deep Q-Network (DQN, [Mnih et al., 2015]) and Dueling Network Architectures (DuDQN, [Wang et al., 2015]) consist of a framework with a static frame skip rate, where the action output from the network is repeated for a fixed number of frames regardless of the current state. In this paper, we propose a new architecture, Dynamic Frame skip Deep Q-Network (DFDQN) which makes the frame skip rate a dynamic learnable parameter. This allows us to choose the number of times an action is to be repeated based on the current state. We show empirically that such a setting improves the performance on relatively harder games like Seaquest.
Asian Journal of Pharmaceutical and Clinical Research
Objectives: The objective of study is to estimate the role of counseling on the diseased patients... more Objectives: The objective of study is to estimate the role of counseling on the diseased patients with asthma and its effects on the medication adherence in relation to their associated side effects on medicines on patients. Methods: The prospective case–control study was carried out at the outpatient department of respiratory department. 190 patients were enrolled for the study of 6 months. Patient counseling and follow-up were done on the basis of knowledge, attitude, and practice (KAP) questionnaire. In 190 subjects, 115 were female and 75 were male and were having the pathological history of cough cold, tuberculosis, hypertension, etc. Results: It was found that counseling causes increase in medication adherence of patients from 28.90% to 71.50% and inhaler adherence from 27.60% to 72.60%. Along with the medication adherence, fewer side effects due to various drugs were encountered such as sore throat, rhinitis, constipation, difficulty in glutition, hand tremor, and weight gain...
The fabrication and characterisation of micro spark gap switch for single shot firing application... more The fabrication and characterisation of micro spark gap switch for single shot firing applications are given in detailed . A circular switch with triggering electrode is realised on alumina substrate and can be integratable easily with the electronics for ignition applications. Circular switch is realised on 25 mil alumina substrate within substrate diameter of 10 mm. The switch measurement shows having repeatable performance of pulse peak current of around 2000 A and less than 100 ns rise time. This article details the design, development including fabrication aspects of spark switch with trigger capabilities along with characterisation of switch on alumina substrates.
The weakening of zonal atmospheric circulation, a widely accepted projection of climate change in... more The weakening of zonal atmospheric circulation, a widely accepted projection of climate change in response to global warming, features a weakening of the Indian Ocean Walker circulation (IWC), with an anomalous ascending motion over the western and anomalous descending motion over the eastern Indian Ocean. The projected IWC weakening has previously been attributed to slower warming in the east than the west, that is, to a positive Indian Ocean Dipole (IOD)-like warming pattern. However, such a warming pattern can also be induced by IWC weakening. As a result, the cause-and-effect relationship cannot be easily determined, and the projected change is poorly constrained and highly uncertain. Here, using a suite of coupled climate model simulations under a high-emission scenario, we find that the IWC slowdown is accompanied by not only a positive IOD-like warming pattern but also anomalous meridional circulation that is associated with anomalous descending motion over the eastern Indian...
Despite being one of the most significant economic contributors of the country, Canada's cons... more Despite being one of the most significant economic contributors of the country, Canada's construction industry is lagging behind other sectors when it comes to labor productivity improvements. The construction industry is very collaborative as a general contractor, will hire trade contractors to perform most of a project's work; meaning low productivity from one contractor can have a domino effect on the shared success of a project. To address this issue and encourage trade contractors to improve their productivity tracking methods, an investigative study was done on the productivity views and tracking methods of various trade contractors. Additionally, an in-depth review was done on four standard tracking methods used in the construction industry: cost codes, benchmarking, the job productivity measurement (JPM) standard, and WorkFace Planning (WFP). The four tracking methods were used as a baseline in comparing the trade contractors' responses, determining gaps within t...
This thesis investigates the engineering economics of interventions to reduce consumer inconvenie... more This thesis investigates the engineering economics of interventions to reduce consumer inconvenience due to unreliable electricity supply in rural India. The work introduces and applies a novel approach to estimate interruption costs as loss in consumer surplus due to restricted consumption of electricity services. Chapter 2 reports an assessment that compares grid extension with distributed generation (DG) alternatives, based on the subsidies they will necessitate, and costs of service interruptions that are appropriate in the rural Indian context. Despite the inclusion of interruption costs, standalone DG does not appear to be competitive with grid extension at distances of less than 17 km. However, backing up unreliable grid service with local DG plants is attractive when reliability is very poor, even in previously electrified villages. Introduction of energy efficient lighting changes these economics, and the threshold for acceptable grid unreliability significantly reduces. Ch...
Adaptation to acute and chronic stress and/or persistent stressors is a subject of wide interest ... more Adaptation to acute and chronic stress and/or persistent stressors is a subject of wide interest in central nervous system disorders. In this context, stress is an effector of change in organismal homeostasis and the response is generated when the brain perceives a potential threat. Herein, we discuss a nuanced and granular view whereby a wide variety of genotoxic and environmental stressors, including aging, genetic risk factors, environmental exposures, and age‐ and lifestyle‐related changes, act as direct insults to cellular, as opposed to organismal, homeostasis. These two concepts of how stressors impact the central nervous system are not mutually exclusive. We discuss how maladaptive stressor‐induced changes in protein connectivity through epichaperomes, disease‐associated pathologic scaffolds composed of tightly bound chaperones, co‐chaperones, and other factors, impact intracellular protein functionality altering phenotypes, that in turn disrupt and remodel brain networks ra...
Deep Reinforcement Learning (DRL) methods have performed well in an increasing numbering of high-... more Deep Reinforcement Learning (DRL) methods have performed well in an increasing numbering of high-dimensional visual decision making domains. Among all such visual decision making problems, those with discrete action spaces often tend to have underlying compositional structure in the said action space. Such action spaces often contain actions such as go left, go up as well as go diagonally up and left (which is a composition of the former two actions). The representations of control policies in such domains have traditionally been modeled without exploiting this inherent compositional structure in the action spaces. We propose a new learning paradigm, Factored Action space Representations (FAR) wherein we decompose a control policy learned using a Deep Reinforcement Learning Algorithm into independent components, analogous to decomposing a vector in terms of some orthogonal basis vectors. This architectural modification of the control policy representation allows the agent to learn a...
Thirty-three military combatants, established on record as alcoholic beverages abusers, were test... more Thirty-three military combatants, established on record as alcoholic beverages abusers, were tested. Nineteen were clinically diagnosed with stage 1 alcohol dependency syndrome, and 14 were not. To test combatants, words or short phrases were quickly flashed on the computer monitor screen. The participants being tested saw, instead of words, a row of 15 random numbers/consonants that the program overlaid over the words/stimuli. Participants pressed a special button at the occurrence of each stimulus on the monitor screen. The reaction was measured from the moment the stimulus was presented until the moment the button was pressed. During diagnosis at the subconscious level, 30 patients showed statistically significant reactions to the word "fear." Especially large statistical differences were observed during testing of the phrase "fear of death" between patients diagnosed with alcohol dependencies and those who were not. For the topic "alcohol," 12 patie...
images are being viewed on the slimmest and the smallest display devices which is a challenge for... more images are being viewed on the slimmest and the smallest display devices which is a challenge for various image resizing techniques and algorithms. Traditional methods have been used to change the height and width of the image which are ignorant to the content of the image. Effective resizing of images should focus on image content more than anything else. A manageable technique called seam carving is used for image and video retargeting. Seam carving is therefore used in the reduction or expansion of the height and width ratio known as the aspect ratio. The most important objects in an image are conserved and the inessential objects are edited by placing seams across, which remove the pixels of that object and hence reduce the size of the image. This method can be used for object removal, image enhancement, reducing the size of image, expanding or enlarging the size of image. This article looks upon the basics of seam carving, its types, its basic algorithm, problems in object excl...
CRISPR-Cas systems consist of a complex ribonucleoprotein (RNP) machinery encoded in prokaryotic ... more CRISPR-Cas systems consist of a complex ribonucleoprotein (RNP) machinery encoded in prokaryotic genomes to confer adaptive immunity against foreign mobile genetic elements. Of these, especially the class 2, Type II CRISPR-Cas9 RNA-guided systems with single protein effector modules have recently received much attention for their application as programmable DNA scissors that can be used for genome editing in eukaryotes. While many studies have concentrated their efforts on improving RNA-mediated DNA targeting with these Type II systems, little is known about the factors that modulate processing or binding of the CRISPR RNA (crRNA) guides and the trans-activating tracrRNA to the nuclease protein Cas9, and whether Cas9 can also potentially interact with other endogenous RNAs encoded within the host genome. Here, we describe RIP-seq as a method to globally identify the direct RNA binding partners of CRISPR-Cas RNPs using the Cas9 nuclease as an example. RIP-seq combines co-immunoprecip...
2019 International Conference on Intelligent Systems and Advanced Computing Sciences (ISACS), 2019
Heart disease is one of the most prominent and dangerous diseases that threaten public health aro... more Heart disease is one of the most prominent and dangerous diseases that threaten public health around the world, often leading to heart attacks and strokes. More recently, the amount of heart disease patients under supervision has been increasing significantly owing to lack of awareness and lifestyle related factors affecting health. There is therefore a need to ensure an effective and scalable solution to effectively find and prevent the heart disease within a short and very specific timeline. At this stage, the performance of four well-known classification algorithms; SVM, Decision Tree, Random Forest and Logistic Regression was evaluated for prediction of heart disease using Apache Spark, a fast and general engine for big data processing with its machine learning library, MLlib for batch data processing. The overall performance comparison was assessed in terms of prediction accuracy, building time and prediction time. Experimental results on processed cleveland data from heart disease dataset show that the highest classification accuracy of 87.50 % was reported using Random Forest with sensitivity and specificity of 86.67 and 88.37 %, respectively. On the other hand, the fast algorithm will be logistic regression.
CRISPR–Cas systems provide bacteria with adaptive immunity against phages and plasmids; however, ... more CRISPR–Cas systems provide bacteria with adaptive immunity against phages and plasmids; however, pathways regulating their activity are not well defined. We recently developed a high-throughput genome-wide method (SorTn-seq) and used this to uncover CRISPR–Cas regulators. Here, we demonstrate that the widespread Rsm/Csr pathway regulates the expression of multiple CRISPR–Cas systems in Serratia (type I-E, I-F and III-A). The main pathway component, RsmA (CsrA), is an RNA-binding post-transcriptional regulator of carbon utilisation, virulence and motility. RsmA binds cas mRNAs and suppresses type I and III CRISPR–Cas interference in addition to adaptation by type I systems. Coregulation of CRISPR–Cas and flagella by the Rsm pathway allows modulation of adaptive immunity when changes in receptor availability would alter susceptibility to flagella-tropic phages. Furthermore, we show that Rsm controls CRISPR–Cas in other genera, suggesting conservation of this regulatory strategy. Final...
The Indo-Pacific warm pool (IPWP) is enclosed by a 28 °C isotherm and plays a vital role in contr... more The Indo-Pacific warm pool (IPWP) is enclosed by a 28 °C isotherm and plays a vital role in controlling atmospheric circulations. However, the effects of changes in regional warm pool sea surface temperatures (SSTs) remain unexplored. We divided the IPWP into the Indian and Pacific sectors and distinguished their responses to natural variability and global warming. Furthermore, we examined the impacts of the interannual variability (IAV) in warm pool SST on the tropical Hadley, Walker, and monsoon circulations. The Hadley circulation was affected by warm pool SST warming, i.e., warmer SSTs over the warm pool strengthened the upward branch of Hadley circulation, whereas the downward branch was respectively weakened and strengthened in the Northern and Southern Hemispheres. Walker circulation was strengthened (weakened) in the warming (natural) mode. Consequently, the Walker circulation is weakened since the natural variability of warm pool SST plays a more dominant role rather than t...
The epichaperome is a new cancer target composed of hyperconnected networks of chaperome members ... more The epichaperome is a new cancer target composed of hyperconnected networks of chaperome members that facilitate cell survival. Cancers with an altered chaperone configuration may be susceptible to epichaperome inhibitors. We developed a flow cytometry-based assay for evaluation and monitoring of epichaperome abundance at the single cell level, with the goal of prospectively identifying patients likely to respond to epichaperome inhibitors, to measure target engagement, and dependency during treatment. As proof of principle, we describe a patient with an unclassified myeloproliferative neoplasm harboring a novel PML-SYK fusion, who progressed to acute myeloid leukemia despite chemotherapy and allogeneic stem cell transplant. The leukemia was identified as having high epichaperome abundance. We obtained compassionate access to an investigational epichaperome inhibitor, PU-H71. After 16 doses, the patient achieved durable complete remission. These encouraging results suggest that furt...
Cancer is often associated with alterations in the chaperome, a collection of chaperones, cochape... more Cancer is often associated with alterations in the chaperome, a collection of chaperones, cochaperones, and other cofactors. Changes in the expression levels of components of the chaperome, in the interaction strength among chaperome components, alterations in chaperome constituency, and in the cellular location of chaperome members, are all hallmarks of cancer. Here we aim to provide an overview on how chemical biology has played a role in deciphering such complexity in the biology of the chaperome in cancer and in other diseases. The focus here is narrow and on pathologic changes in the chaperome executed by enhancing the interaction strength between components of distinct chaperome pathways, specifically between those of HSP90 and HSP70 pathways. We will review chemical tools and chemical probe-based assays, with a focus on HSP90. We will discuss how kinetic binding, not classical equilibrium binding, is most appropriate in the development of drugs and probes for the chaperome in disease. We will then present our view on how chaperome inhibitors may become potential drugs and diagnostics in cancer.
A copper-mediated synthesis of diaryl sulfides utilizing Cu(I)-thiophene-2-carboxylate (CuTC) is ... more A copper-mediated synthesis of diaryl sulfides utilizing Cu(I)-thiophene-2-carboxylate (CuTC) is described. We demonstrate the use of CuTC as a soluble, non-basic catalyst in the coupling of aryl iodides and aryl thiols in the synthesis of synthetically advanced diaryl sulfides. This method allows for the successful coupling of challenging substrates including -substituted and heteroaryl iodides and thiols. Additionally, most of the aryl iodide substrates used here contain the privileged piperazine scaffold bound to a pyrimidine, pyridine, or phenyl ring and thus this method allows for the elaboration of complex piperazine scaffolds into molecules of biological interest. The method described here enables the incorporation of late-stage structural diversity into diaryl sulfides containing the piperazine ring, thus enhancing the number and nature of derivatives available for SAR investigation.
In this Opinion article, we aim to address how cells adapt to stress and the repercussions chroni... more In this Opinion article, we aim to address how cells adapt to stress and the repercussions chronic stress has on cellular function. We consider acute and chronic stress-induced changes at the cellular level, with a focus on a regulator of cellular stress, the chaperome, which is a protein assembly that encompasses molecular chaperones, co-chaperones and other co-factors. We discuss how the chaperome takes on distinct functions under conditions of stress that are executed in ways that differ from the one-on-one cyclic, dynamic functions exhibited by distinct molecular chaperones. We argue that through the formation of multimeric stable chaperome complexes, a state of chaperome hyperconnectivity, or networking, is gained. The role of these chaperome networks is to act as multimolecular scaffolds, a particularly important function in cancer, where they increase the efficacy and functional diversity of several cellular processes. We predict that these concepts will change how we develop...
Stresses associated with disease may pathologically remodel the proteome by both increasing inter... more Stresses associated with disease may pathologically remodel the proteome by both increasing interaction strength and altering interaction partners, resulting in proteome-wide connectivity dysfunctions. Chaperones play an important role in these alterations, but how these changes are executed remains largely unknown. Our study unveils a specific N-glycosylation pattern used by a chaperone, Glucose-regulated protein 94 (GRP94), to alter its conformational fitness and stabilize a state most permissive for stable interactions with proteins at the plasma membrane. This "protein assembly mutation' remodels protein networks and properties of the cell. We show in cells, human specimens, and mouse xenografts that proteome connectivity is restorable by inhibition of the Nglycosylated GRP94 variant. In summary, we provide biochemical evidence for stressor-induced chaperone-mediated protein mis-assemblies and demonstrate how these alterations are actionable in disease.
Deep Reinforcement Learning methods have achieved state of the art performance in learning contro... more Deep Reinforcement Learning methods have achieved state of the art performance in learning control policies for the games in the Atari 2600 domain. One of the important parameters in the Arcade Learning Environment (ALE, [Bellemare et al., 2013]) is the frame skip rate. It decides the granularity at which agents can control game play. A frame skip value of k allows the agent to repeat a selected action k number of times. The current state of the art architectures like Deep Q-Network (DQN, [Mnih et al., 2015]) and Dueling Network Architectures (DuDQN, [Wang et al., 2015]) consist of a framework with a static frame skip rate, where the action output from the network is repeated for a fixed number of frames regardless of the current state. In this paper, we propose a new architecture, Dynamic Frame skip Deep Q-Network (DFDQN) which makes the frame skip rate a dynamic learnable parameter. This allows us to choose the number of times an action is to be repeated based on the current state. We show empirically that such a setting improves the performance on relatively harder games like Seaquest.
Asian Journal of Pharmaceutical and Clinical Research
Objectives: The objective of study is to estimate the role of counseling on the diseased patients... more Objectives: The objective of study is to estimate the role of counseling on the diseased patients with asthma and its effects on the medication adherence in relation to their associated side effects on medicines on patients. Methods: The prospective case–control study was carried out at the outpatient department of respiratory department. 190 patients were enrolled for the study of 6 months. Patient counseling and follow-up were done on the basis of knowledge, attitude, and practice (KAP) questionnaire. In 190 subjects, 115 were female and 75 were male and were having the pathological history of cough cold, tuberculosis, hypertension, etc. Results: It was found that counseling causes increase in medication adherence of patients from 28.90% to 71.50% and inhaler adherence from 27.60% to 72.60%. Along with the medication adherence, fewer side effects due to various drugs were encountered such as sore throat, rhinitis, constipation, difficulty in glutition, hand tremor, and weight gain...
The fabrication and characterisation of micro spark gap switch for single shot firing application... more The fabrication and characterisation of micro spark gap switch for single shot firing applications are given in detailed . A circular switch with triggering electrode is realised on alumina substrate and can be integratable easily with the electronics for ignition applications. Circular switch is realised on 25 mil alumina substrate within substrate diameter of 10 mm. The switch measurement shows having repeatable performance of pulse peak current of around 2000 A and less than 100 ns rise time. This article details the design, development including fabrication aspects of spark switch with trigger capabilities along with characterisation of switch on alumina substrates.
The weakening of zonal atmospheric circulation, a widely accepted projection of climate change in... more The weakening of zonal atmospheric circulation, a widely accepted projection of climate change in response to global warming, features a weakening of the Indian Ocean Walker circulation (IWC), with an anomalous ascending motion over the western and anomalous descending motion over the eastern Indian Ocean. The projected IWC weakening has previously been attributed to slower warming in the east than the west, that is, to a positive Indian Ocean Dipole (IOD)-like warming pattern. However, such a warming pattern can also be induced by IWC weakening. As a result, the cause-and-effect relationship cannot be easily determined, and the projected change is poorly constrained and highly uncertain. Here, using a suite of coupled climate model simulations under a high-emission scenario, we find that the IWC slowdown is accompanied by not only a positive IOD-like warming pattern but also anomalous meridional circulation that is associated with anomalous descending motion over the eastern Indian...
Despite being one of the most significant economic contributors of the country, Canada's cons... more Despite being one of the most significant economic contributors of the country, Canada's construction industry is lagging behind other sectors when it comes to labor productivity improvements. The construction industry is very collaborative as a general contractor, will hire trade contractors to perform most of a project's work; meaning low productivity from one contractor can have a domino effect on the shared success of a project. To address this issue and encourage trade contractors to improve their productivity tracking methods, an investigative study was done on the productivity views and tracking methods of various trade contractors. Additionally, an in-depth review was done on four standard tracking methods used in the construction industry: cost codes, benchmarking, the job productivity measurement (JPM) standard, and WorkFace Planning (WFP). The four tracking methods were used as a baseline in comparing the trade contractors' responses, determining gaps within t...
This thesis investigates the engineering economics of interventions to reduce consumer inconvenie... more This thesis investigates the engineering economics of interventions to reduce consumer inconvenience due to unreliable electricity supply in rural India. The work introduces and applies a novel approach to estimate interruption costs as loss in consumer surplus due to restricted consumption of electricity services. Chapter 2 reports an assessment that compares grid extension with distributed generation (DG) alternatives, based on the subsidies they will necessitate, and costs of service interruptions that are appropriate in the rural Indian context. Despite the inclusion of interruption costs, standalone DG does not appear to be competitive with grid extension at distances of less than 17 km. However, backing up unreliable grid service with local DG plants is attractive when reliability is very poor, even in previously electrified villages. Introduction of energy efficient lighting changes these economics, and the threshold for acceptable grid unreliability significantly reduces. Ch...
Adaptation to acute and chronic stress and/or persistent stressors is a subject of wide interest ... more Adaptation to acute and chronic stress and/or persistent stressors is a subject of wide interest in central nervous system disorders. In this context, stress is an effector of change in organismal homeostasis and the response is generated when the brain perceives a potential threat. Herein, we discuss a nuanced and granular view whereby a wide variety of genotoxic and environmental stressors, including aging, genetic risk factors, environmental exposures, and age‐ and lifestyle‐related changes, act as direct insults to cellular, as opposed to organismal, homeostasis. These two concepts of how stressors impact the central nervous system are not mutually exclusive. We discuss how maladaptive stressor‐induced changes in protein connectivity through epichaperomes, disease‐associated pathologic scaffolds composed of tightly bound chaperones, co‐chaperones, and other factors, impact intracellular protein functionality altering phenotypes, that in turn disrupt and remodel brain networks ra...
Deep Reinforcement Learning (DRL) methods have performed well in an increasing numbering of high-... more Deep Reinforcement Learning (DRL) methods have performed well in an increasing numbering of high-dimensional visual decision making domains. Among all such visual decision making problems, those with discrete action spaces often tend to have underlying compositional structure in the said action space. Such action spaces often contain actions such as go left, go up as well as go diagonally up and left (which is a composition of the former two actions). The representations of control policies in such domains have traditionally been modeled without exploiting this inherent compositional structure in the action spaces. We propose a new learning paradigm, Factored Action space Representations (FAR) wherein we decompose a control policy learned using a Deep Reinforcement Learning Algorithm into independent components, analogous to decomposing a vector in terms of some orthogonal basis vectors. This architectural modification of the control policy representation allows the agent to learn a...
Thirty-three military combatants, established on record as alcoholic beverages abusers, were test... more Thirty-three military combatants, established on record as alcoholic beverages abusers, were tested. Nineteen were clinically diagnosed with stage 1 alcohol dependency syndrome, and 14 were not. To test combatants, words or short phrases were quickly flashed on the computer monitor screen. The participants being tested saw, instead of words, a row of 15 random numbers/consonants that the program overlaid over the words/stimuli. Participants pressed a special button at the occurrence of each stimulus on the monitor screen. The reaction was measured from the moment the stimulus was presented until the moment the button was pressed. During diagnosis at the subconscious level, 30 patients showed statistically significant reactions to the word "fear." Especially large statistical differences were observed during testing of the phrase "fear of death" between patients diagnosed with alcohol dependencies and those who were not. For the topic "alcohol," 12 patie...
images are being viewed on the slimmest and the smallest display devices which is a challenge for... more images are being viewed on the slimmest and the smallest display devices which is a challenge for various image resizing techniques and algorithms. Traditional methods have been used to change the height and width of the image which are ignorant to the content of the image. Effective resizing of images should focus on image content more than anything else. A manageable technique called seam carving is used for image and video retargeting. Seam carving is therefore used in the reduction or expansion of the height and width ratio known as the aspect ratio. The most important objects in an image are conserved and the inessential objects are edited by placing seams across, which remove the pixels of that object and hence reduce the size of the image. This method can be used for object removal, image enhancement, reducing the size of image, expanding or enlarging the size of image. This article looks upon the basics of seam carving, its types, its basic algorithm, problems in object excl...
CRISPR-Cas systems consist of a complex ribonucleoprotein (RNP) machinery encoded in prokaryotic ... more CRISPR-Cas systems consist of a complex ribonucleoprotein (RNP) machinery encoded in prokaryotic genomes to confer adaptive immunity against foreign mobile genetic elements. Of these, especially the class 2, Type II CRISPR-Cas9 RNA-guided systems with single protein effector modules have recently received much attention for their application as programmable DNA scissors that can be used for genome editing in eukaryotes. While many studies have concentrated their efforts on improving RNA-mediated DNA targeting with these Type II systems, little is known about the factors that modulate processing or binding of the CRISPR RNA (crRNA) guides and the trans-activating tracrRNA to the nuclease protein Cas9, and whether Cas9 can also potentially interact with other endogenous RNAs encoded within the host genome. Here, we describe RIP-seq as a method to globally identify the direct RNA binding partners of CRISPR-Cas RNPs using the Cas9 nuclease as an example. RIP-seq combines co-immunoprecip...
2019 International Conference on Intelligent Systems and Advanced Computing Sciences (ISACS), 2019
Heart disease is one of the most prominent and dangerous diseases that threaten public health aro... more Heart disease is one of the most prominent and dangerous diseases that threaten public health around the world, often leading to heart attacks and strokes. More recently, the amount of heart disease patients under supervision has been increasing significantly owing to lack of awareness and lifestyle related factors affecting health. There is therefore a need to ensure an effective and scalable solution to effectively find and prevent the heart disease within a short and very specific timeline. At this stage, the performance of four well-known classification algorithms; SVM, Decision Tree, Random Forest and Logistic Regression was evaluated for prediction of heart disease using Apache Spark, a fast and general engine for big data processing with its machine learning library, MLlib for batch data processing. The overall performance comparison was assessed in terms of prediction accuracy, building time and prediction time. Experimental results on processed cleveland data from heart disease dataset show that the highest classification accuracy of 87.50 % was reported using Random Forest with sensitivity and specificity of 86.67 and 88.37 %, respectively. On the other hand, the fast algorithm will be logistic regression.
CRISPR–Cas systems provide bacteria with adaptive immunity against phages and plasmids; however, ... more CRISPR–Cas systems provide bacteria with adaptive immunity against phages and plasmids; however, pathways regulating their activity are not well defined. We recently developed a high-throughput genome-wide method (SorTn-seq) and used this to uncover CRISPR–Cas regulators. Here, we demonstrate that the widespread Rsm/Csr pathway regulates the expression of multiple CRISPR–Cas systems in Serratia (type I-E, I-F and III-A). The main pathway component, RsmA (CsrA), is an RNA-binding post-transcriptional regulator of carbon utilisation, virulence and motility. RsmA binds cas mRNAs and suppresses type I and III CRISPR–Cas interference in addition to adaptation by type I systems. Coregulation of CRISPR–Cas and flagella by the Rsm pathway allows modulation of adaptive immunity when changes in receptor availability would alter susceptibility to flagella-tropic phages. Furthermore, we show that Rsm controls CRISPR–Cas in other genera, suggesting conservation of this regulatory strategy. Final...
The Indo-Pacific warm pool (IPWP) is enclosed by a 28 °C isotherm and plays a vital role in contr... more The Indo-Pacific warm pool (IPWP) is enclosed by a 28 °C isotherm and plays a vital role in controlling atmospheric circulations. However, the effects of changes in regional warm pool sea surface temperatures (SSTs) remain unexplored. We divided the IPWP into the Indian and Pacific sectors and distinguished their responses to natural variability and global warming. Furthermore, we examined the impacts of the interannual variability (IAV) in warm pool SST on the tropical Hadley, Walker, and monsoon circulations. The Hadley circulation was affected by warm pool SST warming, i.e., warmer SSTs over the warm pool strengthened the upward branch of Hadley circulation, whereas the downward branch was respectively weakened and strengthened in the Northern and Southern Hemispheres. Walker circulation was strengthened (weakened) in the warming (natural) mode. Consequently, the Walker circulation is weakened since the natural variability of warm pool SST plays a more dominant role rather than t...
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Papers by Sahil Sharma