International Journal in Management and Social Science, 2016
Employees are the most important and valuable assets of an organization. Organizations today are ... more Employees are the most important and valuable assets of an organization. Organizations today are doing their best to hold on to their employees. Retaining them is as important as hiring them in the first place. Retention is the next challenge after hiring the employees. Retention is important because to make good people stick in the organization. Stay interview is the new trend in HR. stay interview help to understand employees feeling, perception towards organization. The study was conducted in N.S. InfoTech Hubli one of the finest IT enabled service organization which is located in vidyanagar. The purpose of this paper is to identify the attrition rate, the factors reducing employee turnover and to explore the impact of retention strategies using the stay interview as a tool on employees. The Objectives of the research are to determine the employee turnover at N.S. InfoTech to identify the facilitating factors and hindering factors that makes employee to perform better in organization, to study the impact of few variables and to conduct the stay interview as intervention regarding improvements in retention strategy. The research was carried out in three phases. Phase one we were trying to identify the attrition rate for the year 2014-2015. Phase two was face to face interaction with all the employees in order to understand the facilitating and inhibiting factors for the employees. Stay interview was conducted for 101 employees; with random sampling. Phase three was all about designing and administering questionnaire to understand the impact of few variables on organization as well as employees. The results of the research revealed that employees are happy with working environment; training but employees are expecting betterment in salary, flexible practices and designation. Company should focus on betterment of above parameter to achieve its objectives.
Background: Cyclin-dependent kinase 12 (CDK12) coordinately regulates the transcription, splicing... more Background: Cyclin-dependent kinase 12 (CDK12) coordinately regulates the transcription, splicing, and alternative splicing of several large pre-mRNAs. Defective CDK12 kinase activity has been associated with genomic instability and downregulation of genes in the DNA damage response (DDR) pathway. In addition, CDK12 depletion impairs alternate splicing, a process being increasingly implicated in cancer progression. Associated with Cyclin K (CycK), CDK12 regulates transcription elongation by phosphorylating RNA polymerase II (RNAP II) at S2 in the C-terminal domain (CTD). Considering its role in transcription and RNA processing to maintain genomic stability/integrity in cancer, CDK12 is emerging as a potential therapeutic target to treat cancer. Experimental Procedures: Potent and selective CDK12 inhibitors were identified from multiple series by iterative medicinal chemistry efforts and SAR-based approaches. Early compounds were optimized towards attaining good physicochemical prope...
In the current study, poly(vinyl alcohol) (PVA)/titanium dioxide (TiO2)-based nanocomposite films... more In the current study, poly(vinyl alcohol) (PVA)/titanium dioxide (TiO2)-based nanocomposite films were prepared using the solution-blending and solvent-evaporation techniques. The tensile properties and phase morphology of the prepared PVA/titanium dioxide nanocomposite films were investigated using universal testing machine (UTM) tests and scanning electron microscopy, respectively. Further, the water contact angles and antifungal activities of the composite films and their interactions were evaluated by using Fourier transform infrared spectroscopy (FTIR). The results of UTM tests revealed that the mechanical properties increased up to a proportion of 6% titanium dioxide nanoparticles. The addition of titanium dioxide nanoparticles to the PVA matrix resulted in smooth and homogeneous phase morphology except for the PVA matrix with 4% brahmi plant extract titanium dioxide nanoparticles. The water contact angle and antimicrobial activity confirmed that the hydrophilic nature slightl...
Cyclin-dependent kinase 12 (CDK12) is a transcription-associated protein that plays a critical ro... more Cyclin-dependent kinase 12 (CDK12) is a transcription-associated protein that plays a critical role in DNA damage response, splicing, pre-mRNA processing and is crucial for maintaining genomic stability. CDK12 associated with Cyclin K (CycK) regulates transcription elongation by phosphorylating RNA polymerase II (RNAP II) at Serine 2 (pS2) in the C-terminal domain (CTD). Overexpression of CDK12 in various tumor types suggests the possibility that CDK12 has oncogenic properties, similarly to other transcription-associated kinases. Considering its critical role in transcription and RNA processing, CDK12 is emerging as a potential therapeutic target for cancer. Multiple series of potent and selective CDK12 covalent inhibitors were identified by structure-guided and iterative medicinal chemistry approaches. Early lead compounds were optimized towards achieving high on target potency with good selectivity and desirable drug like properties including pharmacokinetic profile to achieve anti-tumour activity. Optimization of early lead compounds from two distinct chemical series resulted in very potent and highly selective CDK12 covalent inhibitors with desirable oral bioavailability. The covalent mode of action for these biochemically potent compounds has been confirmed by CDK12 target engagement assay in the cellular context. These selective inhibitors showed significant anti-proliferative activity in TNBC and other cancer cell lines including those harbouring ETS fusion. Importantly, cell killing is observed in cancer cells but not in normal cells (RWPE1) with short time (2h) and long-time (72h) exposure of these compounds. Anti-proliferative activity is well correlated with the inhibition of pS2 and down-regulation of a number of DNA damage response genes including BRCA1, RAD51, ATM and FANCI. Consistent with the inhibition of genes involved in DNA damage repair, a highly synergistic anti-proliferative activity was observed when treated in combination with cisplatin and PARP inhibitors. Based on the robust efficacy as a single agent in a TNBC mouse xenograft model with one of the optimized leads, the preclinical candidate exhibiting a greater degree of selectivity is being evaluated for efficacy and tolerability in relevant preclinical models. Citation Format: Ramulu Poddutoori, Sujatha Rajagopalan, Subhendu Mukherjee, Sivapriya Marappan, Samiulla D. S., Sasirekha Sivakumar, Shilpa S Nayak, Ravindra M V, Devaraja TS, Srinivas Kondela, Suraj Tgore, Amit A Dhudashiya, Charamanna K. B, Aravind A B, Amith A, Pavithra S, Hema Sankar Pathange, Thomas Antony, Mahaboobi Jaleel, Sanjeev Giri, Girish Daginakatte, Kavitha Nellore, Shekar Chelur, Murali Ramachandra, Susanta Samajdar. Pharmacological characterization of a preclinical candidate covalently inhibiting CDK12 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4418.
Journal of Epidemiology and Community Health, 2019
BackgroundLow control and high demand in the places where people work has been shown to partially... more BackgroundLow control and high demand in the places where people work has been shown to partially explain why those in lower socioeconomic positions experience poorer health than their counterparts in higher socioeconomic positions. It would seem likely then that experiences of control in the wider living environment, beyond people’s places of work, might also play a role in shaping these health inequalities. Our recent review of theory revealed potential pathways by which low control in the living environment might explain the social patterning of health via low control beliefs and low actual control.MethodsBased on the potential pathways identified in our review of theory, we conducted a systematic review of longitudinal studies on the relationship between low control in the living environment and social inequalities in health published by January 2019, in English.ResultsSix studies were included in the review. Taken together, they provide evidence that lower social positions are ...
Cyclin-dependent kinase 12 (CDK12) is a transcription-associated kinase that participates in vari... more Cyclin-dependent kinase 12 (CDK12) is a transcription-associated kinase that participates in various cellular processes such as DNA damage response, splicing and pre-mRNA processing. In association with Cyclin K (CycK), CDK12 regulates transcription elongation by phosphorylating RNA polymerase II (RNAP II) at Serine 2 in the C-terminal domain (CTD). Overexpression of CDK12 in various tumor types suggests the possibility that CDK12 has oncogenic properties, similarly to other transcription-associated kinases. Considering its critical role in transcription and RNA processing CDK12 is emerging as a potential therapeutic target for cancer. Multiple series of potent and selective CDK12 covalent inhibitors were identified by iterative medicinal chemistry efforts and SAR-based approaches. Early compounds were optimized towards attaining good physicochemical properties, high potency, good selectivity and desirable pharmacokinetic profile to achieve anti-tumour activity. Very potent and high...
Cyclin-dependent kinase 7 (CDK7) is an important constituent of the cellular transcriptional mach... more Cyclin-dependent kinase 7 (CDK7) is an important constituent of the cellular transcriptional machinery, where it phosphorylates the C-terminal domain (CTD) of RNAP polymerase II (RNAPII). Because many tumor types are critically dependent on transcription for maintenance of their oncogenic state, pharmacological modulation of CDK7 kinase activity is considered as an approach to treat cancer. Multiple series of covalent CDK7 inhibitors were identified by iterative medicinal chemistry efforts and SAR based approach. These compounds were optimized towards attaining good physicochemical properties, high potency, good selectivity and desirable pharmacokinetic profile to achieve anti-tumor activity. We have now identified a pre-clinical candidate AU-BGB-002 which is highly potent in inhibiting CDK7 in biochemical as well as cellular assays while fully efficiently engaging the target. In a panel of kinases, AU-BGB-002 shows selectivity for CDK7. A panel of cell lines derived from a diverse ...
Background: Phosphorylation of the RNA polymerase II (RNAPII) in C-terminal domain (CTD) by Cycli... more Background: Phosphorylation of the RNA polymerase II (RNAPII) in C-terminal domain (CTD) by Cyclin-dependent kinase 7 (CDK7) is an important step in cellular transcription process. Hence pharmacological modulation of CDK7 kinase activity is considered as an interesting approach to treat cancers that critically dependent on transcription to maintain their oncogenic state. Experimental procedures: Multiple series of novel covalent CDK7 inhibitors were identified by SBDD approach based on the binding mode of known CDK7 inhibitors to find early hits. Iterative medicinal chemistry efforts were performed to identify several lead compounds by optimizing the initial hits to achieve good physicochemical properties, high potency, good selectivity and desirable pharmacokinetic profile. Summary: Highly potent ATP competitive covalent inhibitors of CDK7 from two distinct chemical series were identified. They show time-dependent inhibition of CDK7 enzyme activity as a proof of covalent binding an...
The present invention discloses an easily alkali soluble polyester comprising at least one dicarb... more The present invention discloses an easily alkali soluble polyester comprising at least one dicarboxylic acid or monoesters thereof or diesters thereof; at least one diol; at least one carboxylic acid anhydride; at least one sodium or lithium based aromatic co-monomer and at least one hydroxyl terminated polyester polyol. The polyester is produced by esterifying at least one dicarboxylic acid or monoesters thereof or diesters thereof and at least one diol alongwith at least one acid anhydride at a temperature in the range of 250 to 290 DEG C and pressure in the range of 0 to 5 kg/cm g; and polycondensing the esterified mixture along with at least one sodium or lithium based aromatic compound and at least one hydroxyl terminated polyether polyol at temperature in the range of 250 to 290 DEG C and under vacuum of 0.1 to 10 torr. The invention further discloses bicomponent filament yarns or staple fibers comprising the above easily alkali soluble polyester as one polymer component and any filament or fiber forming polymer as a second polymer component and process for producing the same.
Cyclin-dependent kinase 7 (CDK7) is an important constituent of the cellular transcriptional mach... more Cyclin-dependent kinase 7 (CDK7) is an important constituent of the cellular transcriptional machinery, where it phosphorylates the C-terminal domain (CTD) of RNAP polymerase II (RNAPII). Because many tumor types are critically dependent on transcription for maintenance of their oncogenic state, pharmacological modulation of CDK7 kinase activity is considered as an approach to treat cancer. Multiple series of CDK7 inhibitors were identified by iterative medicinal chemistry efforts and SAR based approach. Early compounds were optimized towards attaining good physicochemical properties, high potency, good selectivity and desirable pharmacokinetic profile to achieve anti-tumor activity. We have identified compounds from two distinct chemical series that are highly potent in inhibiting CDK7 in biochemical assays. These inhibitors demonstrate time-dependent inhibition of CDK7 indicating covalent nature of binding. The compounds showed potent anti-proliferative activity in cell lines deri...
International Journal in Management and Social Science, 2016
Employees are the most important and valuable assets of an organization. Organizations today are ... more Employees are the most important and valuable assets of an organization. Organizations today are doing their best to hold on to their employees. Retaining them is as important as hiring them in the first place. Retention is the next challenge after hiring the employees. Retention is important because to make good people stick in the organization. Stay interview is the new trend in HR. stay interview help to understand employees feeling, perception towards organization. The study was conducted in N.S. InfoTech Hubli one of the finest IT enabled service organization which is located in vidyanagar. The purpose of this paper is to identify the attrition rate, the factors reducing employee turnover and to explore the impact of retention strategies using the stay interview as a tool on employees. The Objectives of the research are to determine the employee turnover at N.S. InfoTech to identify the facilitating factors and hindering factors that makes employee to perform better in organization, to study the impact of few variables and to conduct the stay interview as intervention regarding improvements in retention strategy. The research was carried out in three phases. Phase one we were trying to identify the attrition rate for the year 2014-2015. Phase two was face to face interaction with all the employees in order to understand the facilitating and inhibiting factors for the employees. Stay interview was conducted for 101 employees; with random sampling. Phase three was all about designing and administering questionnaire to understand the impact of few variables on organization as well as employees. The results of the research revealed that employees are happy with working environment; training but employees are expecting betterment in salary, flexible practices and designation. Company should focus on betterment of above parameter to achieve its objectives.
Background: Cyclin-dependent kinase 12 (CDK12) coordinately regulates the transcription, splicing... more Background: Cyclin-dependent kinase 12 (CDK12) coordinately regulates the transcription, splicing, and alternative splicing of several large pre-mRNAs. Defective CDK12 kinase activity has been associated with genomic instability and downregulation of genes in the DNA damage response (DDR) pathway. In addition, CDK12 depletion impairs alternate splicing, a process being increasingly implicated in cancer progression. Associated with Cyclin K (CycK), CDK12 regulates transcription elongation by phosphorylating RNA polymerase II (RNAP II) at S2 in the C-terminal domain (CTD). Considering its role in transcription and RNA processing to maintain genomic stability/integrity in cancer, CDK12 is emerging as a potential therapeutic target to treat cancer. Experimental Procedures: Potent and selective CDK12 inhibitors were identified from multiple series by iterative medicinal chemistry efforts and SAR-based approaches. Early compounds were optimized towards attaining good physicochemical prope...
In the current study, poly(vinyl alcohol) (PVA)/titanium dioxide (TiO2)-based nanocomposite films... more In the current study, poly(vinyl alcohol) (PVA)/titanium dioxide (TiO2)-based nanocomposite films were prepared using the solution-blending and solvent-evaporation techniques. The tensile properties and phase morphology of the prepared PVA/titanium dioxide nanocomposite films were investigated using universal testing machine (UTM) tests and scanning electron microscopy, respectively. Further, the water contact angles and antifungal activities of the composite films and their interactions were evaluated by using Fourier transform infrared spectroscopy (FTIR). The results of UTM tests revealed that the mechanical properties increased up to a proportion of 6% titanium dioxide nanoparticles. The addition of titanium dioxide nanoparticles to the PVA matrix resulted in smooth and homogeneous phase morphology except for the PVA matrix with 4% brahmi plant extract titanium dioxide nanoparticles. The water contact angle and antimicrobial activity confirmed that the hydrophilic nature slightl...
Cyclin-dependent kinase 12 (CDK12) is a transcription-associated protein that plays a critical ro... more Cyclin-dependent kinase 12 (CDK12) is a transcription-associated protein that plays a critical role in DNA damage response, splicing, pre-mRNA processing and is crucial for maintaining genomic stability. CDK12 associated with Cyclin K (CycK) regulates transcription elongation by phosphorylating RNA polymerase II (RNAP II) at Serine 2 (pS2) in the C-terminal domain (CTD). Overexpression of CDK12 in various tumor types suggests the possibility that CDK12 has oncogenic properties, similarly to other transcription-associated kinases. Considering its critical role in transcription and RNA processing, CDK12 is emerging as a potential therapeutic target for cancer. Multiple series of potent and selective CDK12 covalent inhibitors were identified by structure-guided and iterative medicinal chemistry approaches. Early lead compounds were optimized towards achieving high on target potency with good selectivity and desirable drug like properties including pharmacokinetic profile to achieve anti-tumour activity. Optimization of early lead compounds from two distinct chemical series resulted in very potent and highly selective CDK12 covalent inhibitors with desirable oral bioavailability. The covalent mode of action for these biochemically potent compounds has been confirmed by CDK12 target engagement assay in the cellular context. These selective inhibitors showed significant anti-proliferative activity in TNBC and other cancer cell lines including those harbouring ETS fusion. Importantly, cell killing is observed in cancer cells but not in normal cells (RWPE1) with short time (2h) and long-time (72h) exposure of these compounds. Anti-proliferative activity is well correlated with the inhibition of pS2 and down-regulation of a number of DNA damage response genes including BRCA1, RAD51, ATM and FANCI. Consistent with the inhibition of genes involved in DNA damage repair, a highly synergistic anti-proliferative activity was observed when treated in combination with cisplatin and PARP inhibitors. Based on the robust efficacy as a single agent in a TNBC mouse xenograft model with one of the optimized leads, the preclinical candidate exhibiting a greater degree of selectivity is being evaluated for efficacy and tolerability in relevant preclinical models. Citation Format: Ramulu Poddutoori, Sujatha Rajagopalan, Subhendu Mukherjee, Sivapriya Marappan, Samiulla D. S., Sasirekha Sivakumar, Shilpa S Nayak, Ravindra M V, Devaraja TS, Srinivas Kondela, Suraj Tgore, Amit A Dhudashiya, Charamanna K. B, Aravind A B, Amith A, Pavithra S, Hema Sankar Pathange, Thomas Antony, Mahaboobi Jaleel, Sanjeev Giri, Girish Daginakatte, Kavitha Nellore, Shekar Chelur, Murali Ramachandra, Susanta Samajdar. Pharmacological characterization of a preclinical candidate covalently inhibiting CDK12 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4418.
Journal of Epidemiology and Community Health, 2019
BackgroundLow control and high demand in the places where people work has been shown to partially... more BackgroundLow control and high demand in the places where people work has been shown to partially explain why those in lower socioeconomic positions experience poorer health than their counterparts in higher socioeconomic positions. It would seem likely then that experiences of control in the wider living environment, beyond people’s places of work, might also play a role in shaping these health inequalities. Our recent review of theory revealed potential pathways by which low control in the living environment might explain the social patterning of health via low control beliefs and low actual control.MethodsBased on the potential pathways identified in our review of theory, we conducted a systematic review of longitudinal studies on the relationship between low control in the living environment and social inequalities in health published by January 2019, in English.ResultsSix studies were included in the review. Taken together, they provide evidence that lower social positions are ...
Cyclin-dependent kinase 12 (CDK12) is a transcription-associated kinase that participates in vari... more Cyclin-dependent kinase 12 (CDK12) is a transcription-associated kinase that participates in various cellular processes such as DNA damage response, splicing and pre-mRNA processing. In association with Cyclin K (CycK), CDK12 regulates transcription elongation by phosphorylating RNA polymerase II (RNAP II) at Serine 2 in the C-terminal domain (CTD). Overexpression of CDK12 in various tumor types suggests the possibility that CDK12 has oncogenic properties, similarly to other transcription-associated kinases. Considering its critical role in transcription and RNA processing CDK12 is emerging as a potential therapeutic target for cancer. Multiple series of potent and selective CDK12 covalent inhibitors were identified by iterative medicinal chemistry efforts and SAR-based approaches. Early compounds were optimized towards attaining good physicochemical properties, high potency, good selectivity and desirable pharmacokinetic profile to achieve anti-tumour activity. Very potent and high...
Cyclin-dependent kinase 7 (CDK7) is an important constituent of the cellular transcriptional mach... more Cyclin-dependent kinase 7 (CDK7) is an important constituent of the cellular transcriptional machinery, where it phosphorylates the C-terminal domain (CTD) of RNAP polymerase II (RNAPII). Because many tumor types are critically dependent on transcription for maintenance of their oncogenic state, pharmacological modulation of CDK7 kinase activity is considered as an approach to treat cancer. Multiple series of covalent CDK7 inhibitors were identified by iterative medicinal chemistry efforts and SAR based approach. These compounds were optimized towards attaining good physicochemical properties, high potency, good selectivity and desirable pharmacokinetic profile to achieve anti-tumor activity. We have now identified a pre-clinical candidate AU-BGB-002 which is highly potent in inhibiting CDK7 in biochemical as well as cellular assays while fully efficiently engaging the target. In a panel of kinases, AU-BGB-002 shows selectivity for CDK7. A panel of cell lines derived from a diverse ...
Background: Phosphorylation of the RNA polymerase II (RNAPII) in C-terminal domain (CTD) by Cycli... more Background: Phosphorylation of the RNA polymerase II (RNAPII) in C-terminal domain (CTD) by Cyclin-dependent kinase 7 (CDK7) is an important step in cellular transcription process. Hence pharmacological modulation of CDK7 kinase activity is considered as an interesting approach to treat cancers that critically dependent on transcription to maintain their oncogenic state. Experimental procedures: Multiple series of novel covalent CDK7 inhibitors were identified by SBDD approach based on the binding mode of known CDK7 inhibitors to find early hits. Iterative medicinal chemistry efforts were performed to identify several lead compounds by optimizing the initial hits to achieve good physicochemical properties, high potency, good selectivity and desirable pharmacokinetic profile. Summary: Highly potent ATP competitive covalent inhibitors of CDK7 from two distinct chemical series were identified. They show time-dependent inhibition of CDK7 enzyme activity as a proof of covalent binding an...
The present invention discloses an easily alkali soluble polyester comprising at least one dicarb... more The present invention discloses an easily alkali soluble polyester comprising at least one dicarboxylic acid or monoesters thereof or diesters thereof; at least one diol; at least one carboxylic acid anhydride; at least one sodium or lithium based aromatic co-monomer and at least one hydroxyl terminated polyester polyol. The polyester is produced by esterifying at least one dicarboxylic acid or monoesters thereof or diesters thereof and at least one diol alongwith at least one acid anhydride at a temperature in the range of 250 to 290 DEG C and pressure in the range of 0 to 5 kg/cm g; and polycondensing the esterified mixture along with at least one sodium or lithium based aromatic compound and at least one hydroxyl terminated polyether polyol at temperature in the range of 250 to 290 DEG C and under vacuum of 0.1 to 10 torr. The invention further discloses bicomponent filament yarns or staple fibers comprising the above easily alkali soluble polyester as one polymer component and any filament or fiber forming polymer as a second polymer component and process for producing the same.
Cyclin-dependent kinase 7 (CDK7) is an important constituent of the cellular transcriptional mach... more Cyclin-dependent kinase 7 (CDK7) is an important constituent of the cellular transcriptional machinery, where it phosphorylates the C-terminal domain (CTD) of RNAP polymerase II (RNAPII). Because many tumor types are critically dependent on transcription for maintenance of their oncogenic state, pharmacological modulation of CDK7 kinase activity is considered as an approach to treat cancer. Multiple series of CDK7 inhibitors were identified by iterative medicinal chemistry efforts and SAR based approach. Early compounds were optimized towards attaining good physicochemical properties, high potency, good selectivity and desirable pharmacokinetic profile to achieve anti-tumor activity. We have identified compounds from two distinct chemical series that are highly potent in inhibiting CDK7 in biochemical assays. These inhibitors demonstrate time-dependent inhibition of CDK7 indicating covalent nature of binding. The compounds showed potent anti-proliferative activity in cell lines deri...
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Papers by Shilpa Nayak