alternative mechanism
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2022 ◽  
Author(s):  
Jordan J.J. Phethean ◽  
Martha Papadopoulou ◽  
Alexander L. Peace

ABSTRACT The geodynamic origin of melting anomalies found at the surface, often referred to as “hotspots,” is classically attributed to a mantle plume process. The distribution of hotspots along mid-ocean-ridge spreading systems around the globe, however, questions the universal validity of this concept. Here, the preferential association of hotspots with slow- to intermediate-spreading centers and not fast-spreading centers, an observation contrary to the expected effect of ridge suction forces on upwelling mantle plumes, is explained by a new mechanism for producing melting anomalies at shallow (<2.3 GPa) depths. By combining the effects of both chemical and thermal density changes during partial melting of the mantle (using appropriate latent heat and depth-dependent thermal expansivity parameters), we find that mantle residues experience an overall instantaneous increase in density when melting occurs at <2.3 GPa. This controversial finding is due to thermal contraction of material during melting, which outweighs the chemical buoyancy due to melting at shallow pressures (where thermal expansivities are highest). These dense mantle residues are likely to locally sink beneath spreading centers if ridge suction forces are modest, thus driving an increase in the flow of fertile mantle through the melting window and increasing magmatic production. This leads us to question our understanding of sub–spreading center dynamics, where we now suggest a portion of locally inverted mantle flow results in hotspots. Such inverted flow presents an alternative mechanism to upwelling hot mantle plumes for the generation of excess melt at near-ridge hotspots, i.e., dense downwelling of mantle residue locally increasing the flow of fertile mantle through the melting window. Near-ridge hotspots, therefore, may not require the elevated temperatures commonly invoked to account for excess melting. The proposed mechanism also satisfies counterintuitive observations of ridge-bound hotspots at slow- to intermediate-spreading centers, yet not at fast-spreading centers, where large dynamic ridge suction forces likely overwhelm density-driven downwelling. The lack of observations of such downwelling in numerical modeling studies to date reflects the generally high chemical depletion buoyancy and/or low thermal expansivity parameter values employed in simulations, which we find to be unrepresentative for melting at <2.3 GPa. We therefore invite future studies to review the values used for parameters affecting density changes during melting (e.g., depletion buoyancy, latent heat of melting, specific heat capacity, thermal expansivity), which quite literally have the potential to turn our understanding of mantle dynamics upside down.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Nadezhda A. Potapova ◽  
Alexey S. Kondrashov ◽  
Sergei M. Mirkin

AbstractGenomic inversions come in various sizes. While long inversions are relatively easy to identify by aligning high-quality genome sequences, unambiguous identification of microinversions is more problematic. Here, using a set of extra stringent criteria to distinguish microinversions from other mutational events, we describe microinversions that occurred after the divergence of humans and chimpanzees. In total, we found 59 definite microinversions that range from 17 to 33 nucleotides in length. In majority of them, human genome sequences matched exactly the reverse-complemented chimpanzee genome sequences, implying that the inverted DNA segment was copied precisely. All these microinversions were flanked by perfect or nearly perfect inverted repeats pointing to their key role in their formation. Template switching at inverted repeats during DNA replication was previously discussed as a possible mechanism for the microinversion formation. However, many of definite microinversions found by us cannot be easily explained via template switching owing to the combination of the short length and imperfect nature of their flanking inverted repeats. We propose a novel, alternative mechanism that involves repair of a double-stranded break within the inverting segment via microhomology-mediated break-induced replication, which can consistently explain all definite microinversion events.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Vandita Dar ◽  
Madhvi Sethi ◽  
Saina Baby ◽  
S. Dinesh Kumar ◽  
R. Shrinivas

PurposeThe objective of this paper was twofold-revisiting the in-kind public distribution system (PDS) – India's flagship food security intervention and seeking beneficiary perspectives on its efficacy. The feasibility of cash transfers as an alternative mechanism is also examined, especially in the context of the COVID-19 pandemic.Design/methodology/approachPrimary and secondary data from the southern Indian state of Tamil Nadu were used. In-depth interviews with beneficiaries using phenomenology were conducted to evaluate their perception and willingness to shift to a cash-based PDS in the pre and post-pandemic periods. Secondary district-level data were also used to ascertain institutional preparedness for this shift.FindingsIn-depth interviews of 105 beneficiaries revealed valuable insights, which seem to have significantly changed post-pandemic. Beneficiaries in the post-pandemic period seem much more inclined toward cash transfers, though a combination of cash plus in-kind benefits seems to be strongly preferred. Secondary results pointed out to the lack of institutional preparedness in financial inclusion. The research suggested that while the existing PDS needs to be overhauled, policymakers should look at a model of cash plus in-kind transfers as a probable alternative to pure cash transfers.Originality/valueThere is a dearth of in-depth state-specific studies on beneficiary perception of PDS, and this is important since the economic and sociocultural milieu in each region is unique. Being the only state with universal food security, its experience could yield important insights for other states or even middle or low-income countries similar to India.


2021 ◽  
Author(s):  
Vera Grinkevich ◽  
Vema Aparna ◽  
Karin Fawkner ◽  
Natalia Issaeva ◽  
Virginia Andreotti ◽  
...  

Restoration of the p53 tumor suppressor for personalised cancer therapy is a promising strategy. However, high-affinity MDM2 inhibitors have shown substantial side effects in clinical trials. Thus, elucidation of the molecular mechanisms of action of p53 reactivating molecules with alternative functional principle is of the utmost importance. Here, we report a discovery of a novel allosteric mechanism of p53 reactivation through targeting the p53 N-terminus which blocks both p53/MDM2 and p53/MDM4 interactions. Using biochemical assays and molecular docking, we identified the binding site of two p53 reactivating molecules, RITA and protoporphyrin IX (PpIX). Ion-mobility mass spectrometry revealed that the binding of RITA to serine 33 and serine 37 is responsible for inducing the allosteric shift in p53, which shields the MDM2 binding residues of p53 and prevents its interactions with MDM2 and MDM4. Our results point to an alternative mechanism of blocking p53 interaction with MDM2 and MDM4 and may pave the way for the development of novel allosteric inhibitors of p53/MDM2 and p53/MDM4 interactions.


2021 ◽  
Author(s):  
Juyoung Kim ◽  
Gohta Goshima

Mitosis is a fundamental process in every eukaryote, in which chromosomes are segregated into two daughter cells by the action of the microtubule (MT)-based spindle. Despite this common principle, genes essential for mitosis are variable among organisms. This indicates that the loss of essential genes or bypass-of-essentiality (BOE) occurred multiple times during evolution. While many BOE relationships have been recently revealed experimentally, the BOE of mitosis regulators (BOE-M) has been scarcely reported and how this occurs remains largely unknown. Here, by mutagenesis and subsequent evolutionary repair experiments, we isolated viable fission yeast strains that lacked the entire coding region of Polo-like kinase (Plk), a versatile essential mitotic kinase. The BOE of Plk was enabled by specific mutations in the downstream machinery, including the MT-nucleating gamma-tubulin complex, and more surprisingly, through downregulation of glucose uptake, which is not readily connected to mitosis. The latter bypass was dependent on casein kinase I (CK1), which has not been considered as a major mitotic regulator. Our genetic and phenotypic data suggest that CK1 constitutes an alternative mechanism of MT nucleation, which is normally dominated by Plk. A similar relationship was observed in a human colon cancer cell line. Thus, our study shows that BOE-M can be achieved by simple genetic or environmental changes, consistent with the occurrence of BOE-M during evolution. Furthermore, the identification of BOE-M constitutes a powerful means to uncover a hitherto under-studied mechanism driving mitosis and also hints at the limitations and solutions for selecting chemotherapeutic compounds targeting mitosis.


2021 ◽  
Vol 17 (12) ◽  
pp. e1009583
Author(s):  
Mario Pannunzi ◽  
Thomas Nowotny

When flies explore their environment, they encounter odors in complex, highly intermittent plumes. To navigate a plume and, for example, find food, they must solve several challenges, including reliably identifying mixtures of odorants and their intensities, and discriminating odorant mixtures emanating from a single source from odorants emitted from separate sources and just mixing in the air. Lateral inhibition in the antennal lobe is commonly understood to help solving these challenges. With a computational model of the Drosophila olfactory system, we analyze the utility of an alternative mechanism for solving them: Non-synaptic (“ephaptic”) interactions (NSIs) between olfactory receptor neurons that are stereotypically co-housed in the same sensilla. We find that NSIs improve mixture ratio detection and plume structure sensing and do so more efficiently than the traditionally considered mechanism of lateral inhibition in the antennal lobe. The best performance is achieved when both mechanisms work in synergy. However, we also found that NSIs decrease the dynamic range of co-housed ORNs, especially when they have similar sensitivity to an odorant. These results shed light, from a functional perspective, on the role of NSIs, which are normally avoided between neurons, for instance by myelination.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yue Kris Wu ◽  
Friedemann Zenke

To rapidly process information, neural circuits have to amplify specific activity patterns transiently. How the brain performs this nonlinear operation remains elusive. Hebbian assemblies are one possibility whereby strong recurrent excitatory connections boost neuronal activity. However, such Hebbian amplification is often associated with dynamical slowing of network dynamics, non-transient attractor states, and pathological run-away activity. Feedback inhibition can alleviate these effects but typically linearizes responses and reduces amplification gain. Here we study nonlinear transient amplification (NTA), a plausible alternative mechanism that reconciles strong recurrent excitation with rapid amplification while avoiding the above issues. NTA has two distinct temporal phases. Initially, positive feedback excitation selectively amplifies inputs that exceed a critical threshold. Subsequently, short-term plasticity quenches the run-away dynamics into an inhibition-stabilized network state. By characterizing NTA in supralinear network models, we establish that the resulting onset transients are stimulus selective and well-suited for speedy information processing. Further, we find that excitatory-inhibitory co-tuning widens the parameter regime in which NTA is possible in the absence of persistent activity. In summary, NTA provides a parsimonious explanation for how excitatory-inhibitory co-tuning and short-term plasticity collaborate in recurrent networks to achieve transient amplification.


2021 ◽  
Author(s):  
◽  
Fikriyatul Falashifah

<p>Over the last two decades, Indonesia began to implement Public-Private Partnerships (PPPs) to provide an alternative mechanism for providing public infrastructure. The need to accelerate development, fulfil national demands and address mounting fiscal constraints are the reasons behind choosing PPP approach. One of the infrastructure projects using PPP mechanisms in Indonesia is Central Java Power Plant (CJPP) project, which is claimed to be the largest power plant in Southeast Asia. The project bidding was won by three consortia including ITOCHU Corporation, Adaro Power and J-Power, while the Government of Indonesia provided a guarantee for this project through the Ministry of Finance (MoF) and the Indonesia Infrastructure Guarantee Fund (IIGF). The project is built under Build, Operate, Own, and Transfer (BOOT) PPP model.  In continuing academic research about PPP in general and CJPP in particular, this study was conducted with the aim of exploring critical issues and challenges in implementing PPPs in CJPP project. Three issues were chosen for particular examination, including governance, environment and social issues. This study was conducted by adopting a qualitative approach under a constructivist epistemology to gain meaning and knowledge from certain phenomena or specific circumstances, in this case, by using CJPP as a single case study. Document reviews, semi-structured interviews, and unstructured observation were carried out from July to September 2018 to gain information and perspectives from multilevel stakeholders who are in charge, involved in and were impacted by the implementation of PPP mechanism in CJPP. Stakeholder Analysis and Sustainable Livelihood Approach were taken as the framework for data analysis.  This study found that top-down approach applied to implementing PPP in CJPP project left some governance issues and dynamics about power relations and regulations; conflicting stakeholders’ interests; communication and knowledge gaps; and dualism perspectives for viewing the scheme. The Governments of Central Java and Batang Regency underwent difficulties in structuring and implementing Environmental and Social Impact Assessment (ESIA), or in Bahasa Indonesia known as AMDAL. Meanwhile, coal, the major resource that will be utilised in this project, faces issues surrounding its emissions, stock, and sustainability. Several issues regarding five forms of capital for sustainable livelihood – human capital, social capital, economic capital, natural capital and physical capital – also arose during the project period. These issues included differing perspectives and sentiments among the surrounding societies and economic inequalities, as well as cultural and migration issues.  It is hoped that this research can inform our understanding of PPP implementation, both in policy and in practice. Based on this study, PPP practice at the national level should standardise documents and processes as well as having project assistance. At the regional level, the local government must be more empowered regarding their roles, responsibilities and resource management. Moreover, the impact of PPP on environment and society should be more precisely predicted and managed.</p>


2021 ◽  
Author(s):  
◽  
Fikriyatul Falashifah

<p>Over the last two decades, Indonesia began to implement Public-Private Partnerships (PPPs) to provide an alternative mechanism for providing public infrastructure. The need to accelerate development, fulfil national demands and address mounting fiscal constraints are the reasons behind choosing PPP approach. One of the infrastructure projects using PPP mechanisms in Indonesia is Central Java Power Plant (CJPP) project, which is claimed to be the largest power plant in Southeast Asia. The project bidding was won by three consortia including ITOCHU Corporation, Adaro Power and J-Power, while the Government of Indonesia provided a guarantee for this project through the Ministry of Finance (MoF) and the Indonesia Infrastructure Guarantee Fund (IIGF). The project is built under Build, Operate, Own, and Transfer (BOOT) PPP model.  In continuing academic research about PPP in general and CJPP in particular, this study was conducted with the aim of exploring critical issues and challenges in implementing PPPs in CJPP project. Three issues were chosen for particular examination, including governance, environment and social issues. This study was conducted by adopting a qualitative approach under a constructivist epistemology to gain meaning and knowledge from certain phenomena or specific circumstances, in this case, by using CJPP as a single case study. Document reviews, semi-structured interviews, and unstructured observation were carried out from July to September 2018 to gain information and perspectives from multilevel stakeholders who are in charge, involved in and were impacted by the implementation of PPP mechanism in CJPP. Stakeholder Analysis and Sustainable Livelihood Approach were taken as the framework for data analysis.  This study found that top-down approach applied to implementing PPP in CJPP project left some governance issues and dynamics about power relations and regulations; conflicting stakeholders’ interests; communication and knowledge gaps; and dualism perspectives for viewing the scheme. The Governments of Central Java and Batang Regency underwent difficulties in structuring and implementing Environmental and Social Impact Assessment (ESIA), or in Bahasa Indonesia known as AMDAL. Meanwhile, coal, the major resource that will be utilised in this project, faces issues surrounding its emissions, stock, and sustainability. Several issues regarding five forms of capital for sustainable livelihood – human capital, social capital, economic capital, natural capital and physical capital – also arose during the project period. These issues included differing perspectives and sentiments among the surrounding societies and economic inequalities, as well as cultural and migration issues.  It is hoped that this research can inform our understanding of PPP implementation, both in policy and in practice. Based on this study, PPP practice at the national level should standardise documents and processes as well as having project assistance. At the regional level, the local government must be more empowered regarding their roles, responsibilities and resource management. Moreover, the impact of PPP on environment and society should be more precisely predicted and managed.</p>


2021 ◽  
Vol 03 (06) ◽  
pp. 384-392
Author(s):  
Keltoum BOUKHAROUBA

The administration issues unilateral administrative decisions, which makes it the strong party, ‎ensuring its independence from the administrative judiciary by not interfering in its affairs as ‎it is a public authority‏.‏ Perhaps the best thing that the legislator did was when he approved, alongside the ‎administrative judiciary sector, alternative mechanisms for resolving the dispute amicably in ‎the Civil and Administrative Procedures Law, since the administrative judiciary costs them ‎many and costly difficulties, especially the long and complex procedures, and the difficulty of ‎implementing administrative rulings and judicial decisions.‎ These mechanisms for settling administrative disputes are to solve problems amicably between ‎litigants: conciliation, mediation and arbitration.‎ We will discuss the conciliation mechanism, treating it from the angle of the legal position of ‎the administrative judge as an original party‎


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