Synergy Model Research Articles

'A synergy model of health': an integration of salutogenesis and the health assets model.

This article proposes to advance the connections between salutogenic theory and assets models for health improvement. There is a need to integrate their use in public health and health promotion so that their respective potentials can be fully developed. This requires their synergies to be made more explicit so that a more coherent approach can be taken to their utilization. A mechanism is therefore needed that helps to raise awareness of them and their value as a resource together. Bronfenbrenner's bioecological theory provides one framework that can support better integration of salutogenesis with the applied nature of assets-based models. This paper proposes a new 'synergy model for health' that integrates key concepts associated with salutogenic theory-generalized and specific resistance resources (GRRs/SRRs) and generalized and specific resistance deficits and the sense of coherence (SOC). In doing so, it highlights those GRRs and SRRs which are assets that, either individually or collectively, help to develop a stronger SOC. Higher levels of SOC can then support the transformations of potential resources into available assets (that people can understand, manage and make sense of), capable of producing positive health development. The proposed 'Synergy model of health' aims to contribute to a deeper theoretical understanding of health and development through the integration of the key elements of both salutogenesis and assets models. This can facilitate a better contextualization of the ideas into public health policy and practice by making the salutogenic theory more action-oriented and the assets model more theoretical.

Synergy: a Python library for calculating, analyzing and visualizing drug combination synergy.

Combinations of multiple pharmacological agents can achieve a substantial benefit over treatment with single agents alone. Combinations that achieve 'more than the sum of their parts' are called synergistic. There have been many proposed frameworks to understand and quantify drug combination synergy with different assumptions and domains of applicability. We introduce here synergy, a Python library that (i) implements a broad array of popular synergy models, (ii) provides tools for evaluating confidence intervals and conducting power analysis and (iii) provides standardized tools to analyze and visualize drug combinations and their synergies and antagonisms. synergy is available on all operating systems for Python >=3.5. It is freely available from https://pypi.org/project/synergy, and its source code is available at https://github.com/djwooten/synergy. This software is released under the GNU General Public License, version 3.0 or later. Supplementary data are available at Bioinformatics online.

Peningkatan Peran Perbankan Syariah Dalam Pengembangan Industri Makanan Halal di Indonesia

The halal food industry is one of the sub-sectors in the halal ecosystem which has considerable potential in Indonesia. However, the role of Islamic banking in supporting the development of this sector is still not optimal, especially financing. This study aims to provide alternatives in terms of contracts and financing models that can support Islamic bank financing in the industry. Then can affect increase the role of Islamic banks to support halal food industry in Indonesia. This research is a library research with a qualitative descriptive approach with content analysis techniques. The results show that the role of Islamic banking is currently still minimal in supporting the halal food industry in Indonesia, especially in terms of financing. In terms of financing models, partnership / synergy and community financing models can be alternatives in the agricultural sector. Meanwhile, the linkage and ecosystem-based financing model is suitable to be applied to the food and beverage processing and service industry sectors.

Based on the Emerging E-commerce Ecosystem Synergy and Innovation Mechanism Investigation

E-commerce is a new business model based on Internet information technology, and its internal operation mechanism can be studied in depth from the perspective of the knowledge ecosystem according to the law of knowledge ecology. The various knowledge elements in the e-business knowledge ecosystem interact and influence each other, continue to exchange materials and energy according to specific rules, and develop and circulate autonomously so that users can acquire, transfer, share and sublimate knowledge in the business system. Finally, knowledge innovation and new value creation are realized to complete the final value sublimation. Based on this, this paper elaborates on three aspects of e-business ecosystem system synergy theory, e-business ecosystem, and e-business ecosystem synergy and innovation model for the reference of relevant personnel.

MODEL SINERGI KELEMBAGAAN DALAM PENINGKATAN KEWIRAUSAHAAN MAHASISWA DI UNIVERSITAS MUHAMMADIYAH SUMATERA UTARA

The existence of Small and Medium Enterprises (UKM) in the Indonesian economy has a big role and potential in developing the national and sectoral economy absorbing a large number of workers. The development of UKM in the university environment is one of the responsibilities of the university and is a necessity to involve universities as a driving force for the emergence of young entrepreneurs in the campus environment. The Muhammadiyah University of North Sumatra has formed a special institution that deals with student entrepreneurship issues, namely PUSKIIBI (Center for Entrepreneurship Innovation and Business Incubator). The research was conducted using the independent interview method, collecting institutional documents and institutional policies, and information related to student activities. From the data set and information, the formulation is carried out. Model of Institutional Synergy in Student Entrepreneurship Development at UMSU. This study aims to determine what institutions and the involvement of these institutions in supporting the progress of entrepreneurship in umsu and to create a model of institutional synergy that directly or indirectly synergizes with Puskiibi. From the research results obtained 1) the role of puskiibi as incubator is, access to community and business networking, support from experienced mentors, validation of ideas, infrastructure assistance, access to investors. 2) Related institutions that support the success of student entrepreneurship are SRCC, Study Programs in UMSU, LP2M, Halal Studies Center, and Haki Center. 3) The synergy model that must be developed is the recruitment of start-up candidates obtained from PKM-K participating students who have been netted by SRCC, student essays with downstream potential and student entrepreneurship independent campus participants obtained from Prodi, research lecturers with industrial potential from LP2M and alumni who come to register directly at PUSKIIBI. Furthermore, PUSKIIBI provides assistance, the certificate is only in synergy with the UMSU Halal Study Center and for the management of Trademarks and Patents through the UMSU HAKI Center.

Abstract 550: Determining efficacy of drug combinations identified by unbiased high throughput screening for RAS-mutated colorectal cancer

Abstract Background: Metastatic colorectal cancer (mCRC) is the second leading cause of cancer death in the US. The response rate to current systemic therapies is ~50% and most patients die within 2.5 years from diagnosis of metastasis. With ~5% of patients with mCRC benefiting from immunotherapies, effective therapies for ~95% of patients with mCRC are urgently required. Greater than 50% of patients with mCRC harbor mutations in the oncogenic driver RAS (KRAS, NRAS). As targeting RAS directly is technically challenging for the majority of RAS mutated sites, efforts have been concentrated on targeting MEK, a downstream mediator of RAS. However, targeting MEK with single agent therapy is ineffective in patients with mCRC. Aims: We aimed to perform unbiased high throughput screening (HTS) to identify drugs that, when combined to MEK inhibitors, would enhance their efficacy. Methods: We performed HTS with CRC cells grown in 2D and 3D cell culture using the MEK inhibitor trametinib as a backbone, and two different compound libraries composed of drugs either approved by the FDA or in clinical trials; 1) the NCI oncology set V, and, 2) a custom clinical compound set. Using the Bliss model of synergy, multiple compounds were identified to be synergistic with trametinib. In vitro and in vivo validation of synergy for a specific drug combination, dasatinib with trametinib, were performed. Results: Our unbiased HTS studies demonstrated that combining the SRC inhibitor dasatinib with trametinib was synergistic in both, 2D and 3D, CRC cell culture. This combination was further validated by MTT and colony formation assays. RPPA and western blot analyses of markers for apoptosis and various cell proliferation markers demonstrated that targeting SRC with MEK inhibits cell proliferation and increases cell death in multiple CRC cell lines as compared to single agents. In vivo studies in mice using RAS mutated CRC PDXs and cell lines with these drugs at clinically relevant doses, however, failed to demonstrate significant tumor growth inhibition or tumor regression. Conclusions: Although our unbiased HTS and other in vitro validation studies demonstrated that combining dasatinib and trametinib can enhance the efficacy of MEK targeted therapy in RAS mutated mCRC cells, careful in vivo preclinical studies failed to demonstrate enhanced efficacy of combining these two drugs. These studies highlight the need for performing careful in vivo preclinical studies as a prerequisite to translate in vitro findings into clinical studies. Further, our studies emphasize the importance for performing in vivo studies using drug doses that reflect clinically achievable doses in humans to identify therapies, either single or in combination, that may finally benefit our patients. This study also exemplifies the importance of publishing negative data so that others can pursue alternative strategies. Citation Format: Fan Fan, Reid Powell, Jason Roszik, Rui Wang, Xiangcang Ye, Clifford Stephan, Lee Ellis, Rajat Bhattacharya. Determining efficacy of drug combinations identified by unbiased high throughput screening for RAS-mutated colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 550.

Abstract 6226: Sapanisertib interferes with the NRF2-mediated stress response to synergize with Obatoclax and extend AT/RT survival

Abstract Atypical teratoid rhabdoid tumors (AT/RT) are the most common malignant brain tumors of infancy, highly resistant to all therapies, and responsible for one of the greatest numbers of life years lost due to cancer. We have previously demonstrated that Sapanisertib combines synergistically with cisplatin to extend survival in AT/RT. To understand the mechanisms underlying this synergy and to identify further novel combination therapies to improve AT/RT survival, we performed RNASeq on AT/RT cell models 4 hours after Sapanisertib treatment. Pathway analysis revealed that Sapanisertib disrupts the NRF2-mediated stress response and apoptotic signaling pathway leading to a pro-death phenotype. Activating mutations in the NRF2 coding gene, NFE2L2, have been identified as a possible biomarker predicting Sapanisertib efficacy in lung cancer clinical trials. Short hairpin knockdown of NRF2 led to decreased expression of the anti-apoptotic proteins MCL-1, BCL-2, and BCL-xL suggesting that interfering with NRF2 may drive this pro-death phenotype in AT/RT. Obatoclax is a synthetic small molecule inhibitor of the BCL-2 family of proteins that was well tolerated in phase II clinical trials and readily crosses the blood brain barrier. Obatoclax treatment of NRF2 knockdown AT/RT cell models slows cell growth, induces high rates of apoptosis, and leads to increased oxidative stress compared to short hairpin scramble controls (cell viability assay, t-test p<0.05; ANNEXIN V cell sorting assay t-test p<0.05, MUSE oxidative stress assay t-test p<0.05). We treated AT/RT cell models with Sapanisertib and showed that treatment decreases expression of NRF2 and MCL-1 (western blot). Sapanisertib combines synergistically with Obatoclax to increase oxidative stress, slow cell growth, and increase apoptosis (MUSE oxidative stress assay ANOVA p<0.05; cell viability assay, ANOVA p<0.05; ANNEXIN V cell sorting assay ANOVA p<0.05, Compusyn model of synergy, CI<1.0). We next developed orthotopic mouse models of AT/RT using our luciferase-labeled CHLA06 and BT37 AT/RT cell models. We administered Sapinisertib and Obatoclax using mouse equivalent dosing to human clinical trials (Sapinisertib 6mg/kg oral weekly, Obatoclax 10mg/kg oral twice a week). Combination treatment was well tolerated and more than doubled median survival. Our data supports a new clinical trial combining Sapinisertib with Obatoclax to extend survival in AT/RT. Citation Format: Ashlyn Parkhurst, Sabrina Wang, Harpreet Kaur, Antje Arnold, Charles Eberhart, Eric Raabe, Jeffrey Rubens. Sapanisertib interferes with the NRF2-mediated stress response to synergize with Obatoclax and extend AT/RT survival [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6226.

Airportlization: The Inevitable Choice of the Integration and Innovation of the exhibition Industry in the Age of Traffic Economy——Practical observation in China

The Internet revolution has had a significant impact on the global economy and society. Human beings are moving from the industrial age to information civilization. As one of the representatives of the new economic form in information civilization, the flow economy will become a new economic development model. Both the exhibition economy and the airport economy have the attributes of flow economy, and both of them are developing rapidly in China. They both are in a state of integration and development. The integration of exhibition economy and airport economy is based on the functional synergy of industrial chain integration, and the spatial integration of urban exhibition clusters and airport economic zones. Based on the theory of industrial chain integration, industrial integration and economic symbiosis, this paper puts forward the concept of the integration of exhibition economy and airport economy. We try to construct functional synergy model and spatial integration model, and propose the mechanism of industry chain sharing, co-governance and symbiosis and comprehensive cost-oriented mechanism. Finally, suggestions were made on the location selection of the airport exhibition industry, the exhibition industry and the airport industry linkage, and the regional competition and cooperation of the airport exhibition industry.

Characterization of the Adaptation to Visuomotor Rotations in the Muscle Synergies Space.

The adaptation to visuomotor rotations is one of the most studied paradigms of motor learning. Previous literature has presented evidence of a dependency between the process of adaptation to visuomotor rotations and the constrains dictated by the workspace of the biological actuators, the muscles, and their co-activation strategies, modeled using muscle synergies analysis. To better understand this relationship, we asked a sample of healthy individuals (N = 7) to perform two experiments aiming at characterizing the adaptation to visuomotor rotations in terms of rotations of the activation space of the muscle synergies during isometric reaching tasks. In both experiments, subjects were asked to adapt to visual rotations altering the position mapping between the force exerted on a fixed manipulandum and the movement of a cursor on a screen. In the first experiment subjects adapted to three different visuomotor rotation angles (30°, 40°, and 50° clockwise) applied to the whole experimental workspace. In the second experiment subjects adapted to a single visuomotor rotation angle (45° clockwise) applied to eight different sub-spaces of the whole workspace, while also performing movements in the rest of the unperturbed workspace. The results from the first experiment confirmed the hypothesis that visuomotor rotations induce rotations in the synergies activation workspace that are proportional to the visuomotor rotation angle. The results from the second experiment showed that rotations affecting limited sub-spaces of the whole workspace are adapted for by rotating only the synergies involved in the movement, with an angle proportional to the distance between the preferred angle of the synergy and the sub-space covered by the rotation. Moreover, we show that the activation of a synergy is only rotated when the sub-space covered by the visual perturbation is applied at the boundaries of the workspace of the synergy. We found these results to be consistent across subjects, synergies and sub-spaces. Moreover, we found a correlation between synergies and muscle rotations further confirming that the adaptation process can be well described, at the neuromuscular level, using the muscle synergies model. These results provide information on how visuomotor rotations can be used to induce a desired neuromuscular response.

Combating COVID-19 through Collaborative Governance: Lessons from East Asia

Collaborative governance plays a significant role in crisis management and greatly contributes to the fight against COVID-19. This article demonstrates how East Asia effectively combats COVID-19 through collaboration with enterprises, nonprofit organizations, and citizens. By comparing different countries’ responses, this study proposes three different types of collaborative governance models employed in combating the pandemic, namely the Chinese state-led cooperation model, South Korea's state-society synergy model, and Japan's social voluntary cooperation model. The findings demonstrate that there is no one-size-fits-all model to respond to the COVID-19 crisis. The specific response initiative that the government adopts is shaped by its state intervention and coercion capacity, as well as the social voluntary cooperation norm. Each country should take anti-pandemic measures based on its specific conditions. Achieving a balance between preventing the pandemic and maintaining social economic development is a challenge for governments. The three collaboration models drawn from the East Asian experience provide valuable lessons for combating the global pandemic and future crises.

The synergy model of village development based on environmental education (biotic approach) in Indonesia perspective of Law Number 6 of 2014

This research is driven from the ineffectiveness of village empowerment in the North Coast of Central Java (Pemalang, Tegal Regency, Tegal City, Pekalongan, and Batang), especially in environmental issues. In fact, the environment is an important part of village development and has the most important contribution to a prosperous independent community according to Law No. 6 of 2014 concerning Villages (Village Law). Environmental development (biotic and abiotic) has a very significant role, and humans as one of the biotic components place a strategic position in the development of the environment in the village. This study aims to produce a synergistic model that combines legal instruments, implementation, and environmental education in rural development. Chamblis and Seidman’s theories (about Law and Society) are used in this study and this study emphasizes that: (1) laws and regulations should be used to achieve social welfare and justice, including in environmental terms, but in fact this is not maximally done, (2) village development as a mandate of the Village Law on the North Coast has not been oriented towards environmental development, so that the use of village funds is ineffective, and (3) the synergy model of village development emphasizes progressive legal principles as one of the tools to encourage law enforcement which is more effective.

Linguistic and Cognitive Analysis of Inter-Cultural Business Discourse from the Perspective of “Dialogue of Cultures” in the Formation of Inter-Cultural Communicative Competence

The article discusses the creation of a qualitatively new educational system in intercultural business communication, capable of providing real interaction between specialists in the global cultural space. Under the current conditions of expanding international cooperation, the humanities specialist must speak a foreign language at a fundamentally new level as an instrument of professional intercultural communicative competence. The aforesaid determines the existence of contradictions between the provisions developed in linguistics and linguistic didactics concerning the theory of intercultural communication and methods of teaching foreign students the Business Russian Language and the lack of their integration and extrapolation in the training of foreign students for interaction in the business sphere of communication. The question of interest is what happens to a linguistic personality when it enters a "foreign" environment undergoing the processes of cognitive consciousness transformation. Based on the studies of the cultural synergy model in the formation of intercultural communicative competence of foreign citizens in business communication, it is concluded that the possession of a foreign-language code that allows a successful intercultural professional interaction requires knowledge of a “foreign” culture and determines the specifics of the social and business behavior of the speakers of this culture. In the “native" culture, a linguistic personality assimilates language through reality, and in a "foreign” culture, the reality is assimilated through language. In this case, the interaction process of communication participants is considered as a complex synergetic system, in which the traditions accepted in the native culture are neutralized and the traditions accepted in the culture of business partners are updated.

Abstract B20: Unbiased high-throughput screenings to identify combination therapies targeting RAS-mutated colorectal cancer

Abstract Introduction: Colorectal cancer (CRC) is the second leading cause of cancer death in the US with ~50,000 deaths estimated this year. Although the median overall survival for patients with unresectable metastatic CRC (mCRC) has modestly improved, the response rate to current combination systemic therapies is ~50% and most patients die of their disease within 2.5 years of the diagnosis of metastasis. Among new therapeutic approaches, immunotherapies have been shown to be effective in only a subset of patients (4-5%) with mCRC with DNA mismatch repair defects. Greater than 50% of patients with mCRC harbor mutations in the oncogenic driver RAS (KRAS, NRAS). As targeting RAS directly is technically challenging, efforts have been concentrated on targeting MEK, a downstream mediator of RAS. However, targeting MEK with single-agent therapy is ineffective in patients with mCRC. We hypothesized that MEK-targeted therapy in patients with mCRC will be most effective when combined with other agents, either chemotherapy or targeted therapy, identified by unbiased high-throughput screening (HTS) approaches. Methods: We performed HTS with CRC cells grown in 2D and 3D cell culture using a MEK inhibitor (approved by the FDA for melanoma) as a backbone, and two different clinically “ready” compound libraries: 1) the NCI oncology set of approved compounds and 2) a custom clinical compound set consisting of compounds either approved by the FDA or in clinical trials. Instead of predicting effective combinations, these unbiased HTS studies allowed the biology of CRC cells to identify the most effective drug combinations. Using the Bliss model of synergy, multiple compounds were identified to be synergistic with the MEK inhibitor. These combinations were further validated in multiple CRC cell lines by examining the effects of the combinations on CRC cell growth and apoptosis. Results: Our unbiased 2D and 3D HTS approaches demonstrated that combining SRC inhibitors with MEK inhibitors is synergistic in 2D and 3D CRC cell culture. This combination was further validated by various growth assays, including MTT and colony formation assays. Further analyses of markers for apoptosis by FACS and Western blotting indicated that targeting SRC with MEK leads to increases in cell death in multiple CRC cell lines as compared to single agents. Conclusions: Based on our unbiased HTS and further validation studies in vitro, we conclude that combining SRC and MEK inhibitors can potentially enhance the efficacy of MEK-targeted therapy in patients with RAS-mutated mCRC. Citation Format: Reid Powell, Fan Fan, Mary Sobieski, David Brunell, Rui Wang, Xiangcang Ye, Clifford Stephan, Lee M. Ellis, Rajat Bhattacharya. Unbiased high-throughput screenings to identify combination therapies targeting RAS-mutated colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr B20.

The Synergy Model for Strengthening the Productivity of Indonesian Halal Industry

Halal industry has become a new commodity that is favoured by all countries around the world, including Indonesia. The main challenge of halal industry development is strengthening its position as a producer in the global halal industry market. This study aims to investigate the number of policy proposals relating to strengthening the productivity of the halal industry in Indonesia and then develop a model of synergy over this matter. This study uses a qualitative study approach, with literature review, observation and interview as data collection methods. The results obtained from this study include several things, specifically; the focus of economic development in Indonesia is fundamentally still focused on the processed industry, which incidentally is dominated by imported raw materials. Based on the results of the analysis of the discussion, the implications of these studies is providing input for authorities such as BPJH, MUI and related ministries to adjust the regulation that address the main business challenge of halal industry. Besides, the government should give special authority to state-owned and private sharia banks to finance the halal industries and agricultural to support their sustainable development.

SYNERGY OF SHARIA BANKS AND FINANCIAL TECHNOLOGY IN THE DEVELOPMENT OF MICRO, SMALL AND MEDIUM BUSINESSES IN INDONESIA

ABSTRACTThe purpose of this study is to analyze the synergy between sharia bank and fintech to effort and develop micro, small and medium enterprises (MSMEs) in Indonesia. Data and information were obtained through interview to expert respondents in their fields such as BNI Syariah, Ammana Fintek Syariah and the Otoritas Jasa Keuangan (OJK). This study has been conducted from July 2018 to March 2019. To provide a deep understanding, this study uses a qualitative approach. The results of the study to show that the opportunity to create synergy between Sharia Bank and Sharia Fintech in order to develop MSMEs in Indonesia is still very wide open. This synergy can be done through several existing patterns or synergy models, including through cross-selling schemes, channeling, references, shadow investors, outsourcing platform and Fintech consortium. The benefits of this synergy include empowering MSMEs, facilitating financial services that are practical, comfortable, safe, have speed, sophistication and up-to-date and are more efficient. The challenges ahead are in terms of human resources competence and support from regulators for policy relaxation. Risks that must be properly mitigated from these synergies, such as the risk of credibility, technology, default and operations.KEYWORDS: Financial Technology (Fintech); Micro; Small and Medium Enterprises; Sharia Bank, Synergy.

A pharmacodynamic model of clinical synergy in multiple myeloma.

BackgroundMultiagent therapies, due to their ability to delay or overcome resistance, are a hallmark of treatment in multiple myeloma (MM). The growing number of therapeutic options in MM requires high-throughput combination screening tools to better allocate treatment, and facilitate personalized therapy.MethodsA second-order drug response model was employed to fit patient-specific ex vivo responses of 203 MM patients to single-agent models. A novel pharmacodynamic model, developed to account for two-way combination effects, was tested with 130 two-drug combinations. We have demonstrated that this model is sufficiently parameterized by single-agent and fixed-ratio combination responses, by validating model estimates with ex vivo combination responses for different concentration ratios, using a checkerboard assay. This new model reconciles ex vivo observations from both Loewe and BLISS synergy models, by accounting for the dimension of time, as opposed to focusing on arbitrary time-points or drug effect. Clinical outcomes of patients were simulated by coupling patient-specific drug combination models with pharmacokinetic data.FindingsCombination screening showed 1 in 5 combinations (21.43% by LD50, 18.42% by AUC) were synergistic ex vivo with statistical significance (P < 0.05), but clinical synergy was predicted for only 1 in 10 combinations (8.69%), which was attributed to the role of pharmacokinetics and dosing schedules.InterpretationThe proposed framework can inform clinical decisions from ex vivo observations, thus providing a path toward personalized therapy using combination regimens.FundingThis research was funded by the H. Lee Moffitt Cancer Center Physical Sciences in Oncology (PSOC) Grant (1U54CA193489-01A1) and by H. Lee Moffitt Cancer Center's Team Science Grant. This work has been supported in part by the PSOC Pilot Project Award (5U54CA193489-04), the Translational Research Core Facility at the H. Lee Moffitt Cancer Center & Research Institute, an NCI-designated Comprehensive Cancer Center (P30-CA076292), the Pentecost Family Foundation, and Miles for Moffitt Foundation.

Emission Inventory of Pollutants (CO, SO2, PM2.5, and NOX) In Jakarta Indonesia

Emission inventory of pollutants (CO, SO2, PM2,5, and NOx) from various sectors included power plants, road transportation, industry, and residential and commercial was conducted in Jakarta for the year 2005-2015. Emissions load of these pollutants was calculated using Gains (Greenhouse gas model - Air pollution Interactions and Synergies) model, based on energy used. Control technology was also applied for pollutants emitted from power plant, industry as well as residential and commercial, while control of EURO II and EURO III were considered for transportation sector. Emission inventory result shows that in 2015, the total emission load for NOx, and CO were estimated around 52.9 kton and 143.9 kton respectively. The biggest contributor to these pollutants were from road transportation sector which contributed of 57%, and 93% for NOx, and CO respectively. From transportation sector, heavy duty vehicles is the biggest contributor of NOx and BC emission, while for CO is mostly emitted from motorcycles. While total emission load for PM2.5 in Jakarta is about 4.6 kton, and it is mostly emitted from road transportation and industrial combustion sectors which are 2.1 kton (46%) and 0.4 kton (43%), respectively. The heavy duty vehicles was still the highest contributor of PM2.5 emission in the transport sector. The total SO2 emission load is 19.7 kton, and it is mostly released from industrial combustion that contribute almost 67% of total emission.

Analysis of synergy degree and its influencing factors in hydropower EPC project management

The use of engineering procurement construction (EPC) mode is currently a trend in hydropower engineering construction. The clarification of the internal relationship between hydropower EPC projects and the realization of synergy has great significance in improving management efficiency and implementation effect. In this work, a three-dimensional system and a system model of hydropower EPC project management synergy are constructed. The mechanism and factors that influence the degree of management synergy are analyzed on the basis of management synergy theory. Furthermore, the evaluation index system and the degree of synergy model are established, and grey relational analysis is utilized to identify the key factors that affect the synergy degree. Thus, this study aims to facilitate the hydropower EPC project management synergy, provide a quantitative method for synergy degree evaluation, and propose corresponding promotion strategies. Results show that the order degree of each subsystem presents a steady upward trend. Specifically, the order degree of the subsystem at the trial operation stage is low, which is the major restriction on the further improvement of the synergy degree of EPC project management. The key factors in improving the synergy level of hydropower EPC project management are mainly concentrated in the information and organization synergy subsystems, including the construction degree of information platform, the performance of functions, the timeliness of information transfer, and the functions of the information platform.

Music as Synergy and Non-Classical Model of Man

The article explores the phenomenon of music from the viewpoint of Man. In the philosophy of music, the connection with man is getting relevant, replacing the positivism, as well as the speculatism, common to music theories in the past, when formal logical methods were used.The article focuses on the connection between man’s personal experience, his or her anthropological energy, that is the one that comes from the innermost foundations and utmost underlying feelings of the person (horror, pain, happiness, delight, and self-transcendence), and specific musical energy. In this rendering, we rest on the philosophical concept of the outstanding modern Russian thinker Sergey Khoruzhy. He describes man as an energetic entity formed by a limit-experience, which is the experience of reaching the limits of existence and consciousness. The synergistic approach to man continues the non-classical philosophical tradition of building the model of man using the categories like “energy”, “self-practice”, “limit-experience”, “constitution of man” and excluding the categories like “entity”, “substance”, “subject” present in the classical vision of man in European philosophy of the 17th—19th centuries.The anthropological component of the non-classical synergistic concept of music includes the comprehension of man through a certain typification of man’s striving to reach the limits. This philosophical anthropology depicts man opening up to the ontological, ontical and virtual limits.Music, as such synergy, stands for a projection of man, thus becoming the music of ontological, ontical and virtual striving. From this point of view, not only a specific concept of music is formed, different from other concepts, such as the concepts of music as a number and as an expression, but also an approach to the entire historical musical legacy and to musical practice, including composer’s, performer’s and listener’s activities.

Olaparib Combined with an ATR or Chk1 Inhibitor as a Treatment Strategy for Acquired Olaparib-Resistant BRCA1 Mutant Ovarian Cells.

Objective: Despite the promise of PARP inhibitors (PARPi) for treating BRCA1/2 mutated ovarian cancer (OC), drug resistance invariably develops. We hypothesized rationale drug combinations, targeting key molecules in DNA repair pathways and the cell cycle may be synergistic and overcome acquired PARPi resistance. Methods: Drug sensitivity to PARPi alone and in combination with inhibitors of key DNA repair and cell cycle proteins, including ATR (VE-821), Chk1 (MK-8776), Wee1 (MK-1775), RAD51 (RI-1) was assessed in PARPi-sensitive (UWB1) and -resistant (UWB1-R) gBRCA1 mutant OC cell lines using a cell proliferation assay. The Bliss synergy model was used to estimate the two-drug combination effect and pharmacologic synergy (Bliss score ≥ 0) or antagonistic (Bliss score ≥ 0) response of the PARPi in combination with the inhibitors. Results: IC50 for olaparib alone was 1.6 ± 0.9 µM compared to 3.4 ± 0.6 µM (p = 0.05) for UWB1 and UWB1-R cells, respectively. UWB1-R demonstrated increased sensitivity to ATRi (p = 0.04) compared to UWB1. Olaparib (0.3–1.25 µM) and ATRi (0.8–2.5 µM) were synergistic with Bliss scores of 17.2 ± 0.2, 11.9 ± 0.6 for UWB1 and UWB1-R cells, respectively. Olaparib (0.3–1.25 µM) and Chk1i(0.05–1.25 µM) were synergistic with Bliss scores of 8.3 ± 1.6, 5.7 ± 2.9 for UWB1 and UWB1-R cells, respectively. Conclusions: Combining an ATRi or Chk1i with olaparib is synergistic in both PARPi-sensitive and -resistant BRCA1 mutated OC cell models, and are rationale combinations for further clinical development.