Patterns Of Flexibility Research Articles

Recognizing the ideal patterns of strategic flexibility, IT strategy and business performance: a cluster analysis approach

PurposeIn spite of intensive research that explained the strategic flexibility-performance and information technology (IT) strategy-performance relationships, there is a little insight regarding how these notions ideally affect business performance. Accordingly, this study attempts to investigate how businesses can translate IT directions and strategic practices into actual increases in business performance. More precisely, the primary purpose of this paper is to explore the influential role of strategic flexibility and IT strategy on business performance considering balanced scorecard (BSC) dimensions in the context of the tourism industry.Design/methodology/approachAn empirical investigation of 331 tourism businesses was performed to explore the relationship between strategic flexibility, IT strategy and business performance. A non-probability convenience sampling was applied to select the sample. Factor analysis, descriptive statistics and cluster analysis were used to analyze the data.FindingsThe findings include the clustering of the studied businesses in terms of strategic flexibility and IT strategy. A cluster analysis based on strategic flexibility indicates that businesses can be divided into four main clusters, and based on IT strategy, they can be classified in three main clusters. The results show that businesses with a high level of strategic flexibility and a high level of IT strategic practices have high performance. More importantly, it was known that proactiveness and strategic use of IT have more predictor role on performance.Originality/valueA review of the strategic management literature reveals a lack of empirical studies that adequately explore the significant roles of strategic flexibility and IT strategy on business performance in the tourism industry. This paper provides actionable insights into these two main determinants that explain why some tourism businesses outperform others. The primary contribution of this study is to address the gap in our understanding of the interconnections between strategic flexibility, IT strategy and business performance through cluster analysis in the tourism industry.

Dilemmas and Breakthroughs in the Application of the Principle of Common but Differentiated Responsibilities in the Context of COP28

The 28th Conference of the Parties to the United Nations Framework Convention on Climate Change (UNFCCC) to be held in Dubai, UAE, in 2023 has reached the “UAE Consensus”, which symbolizes that the principle of common but differentiated responsibilities has entered into a new stage, presenting a new pattern of flexibility, procedure and dynamism. However, the problems that still exist in the Conference mean that the principle of common but differentiated responsibilities is still in the process of being realized, and there are still dilemmas such as uncertainty about the legal attributes of the principle, the lack of a specific system to ensure its implementation, and the insufficient capacity of developing countries in terms of financial and technical support. Based on the above, we would like to put forward some suggestions for improving the application of the principle of common but differentiated responsibilities in China: firstly, the status of the principle should be clarified; secondly, a system should be set up to ensure its implementation; and lastly, the provisions on capacity-building for developing countries in terms of financial support and technical assistance should be fine-tuned. Under the current situation, guaranteeing the realization of the principle of common but differentiated responsibilities will be of great significance to the containment and improvement of global climate change.

Probing heterogeneity to identify individualized treatment approaches in autism: Specific clusters of executive function challenges link to distinct co-occurring mental health problems.

Many autistic people struggle with mental health problems like anxiety, depression, inattention, and aggression, which can be challenging to treat. Executive function challenges, which impact many autistic individuals, may serve as a risk factor for mental health problems or make treating mental health conditions more difficult. While some people respond well to medication or therapy, others do not. This study tried to understand if there are different subgroups of autistic young people who may have similar patterns of executive function strengths and challenges-like flexibility, planning, self-monitoring, and emotion regulation. Then, we investigated whether executive function subgroups were related to mental health problems in autistic youth. We found three different types of executive function subgroups in autistic youth, each with different patterns of mental health problems. This helps us identify specific profiles of executive function strengths and challenges that may be helpful with identifying personalized supports, services, and treatment strategies for mental health conditions.

Modeling brain network flexibility in networks of coupled oscillators: a feasibility study

Modeling the functionality of the human brain is a major goal in neuroscience for which many powerful methodologies have been developed over the last decade. The impact of working memory and the associated brain regions on the brain dynamics is of particular interest due to their connection with many functions and malfunctions in the brain. In this context, the concept of brain flexibility has been developed for the characterization of brain functionality. We discuss emergence of brain flexibility that is commonly measured by the identification of changes in the cluster structure of co-active brain regions. We provide evidence that brain flexibility can be modeled by a system of coupled FitzHugh-Nagumo oscillators where the network structure is obtained from human brain Diffusion Tensor Imaging (DTI). Additionally, we propose a straightforward and computationally efficient alternative macroscopic measure, which is derived from the Pearson distance of functional brain matrices. This metric exhibits similarities to the established patterns of brain template flexibility that have been observed in prior investigations. Furthermore, we explore the significance of the brain’s network structure and the strength of connections between network nodes or brain regions associated with working memory in the observation of patterns in networks flexibility. This work enriches our understanding of the interplay between the structure and function of dynamic brain networks and proposes a modeling strategy to study brain flexibility.

Comparison of the Phenotypic Flexibility of Muscle and Body Condition of Migrant and Resident White-Crowned Sparrows.

AbstractSeasonally breeding birds express variations of traits (phenotypic flexibility) throughout their life history stages that represent adaptations to environmental conditions. Changes of body condition during migration have been well studied, whereas alterations of skeletal and cardiac muscles, body mass, and fat scores have yet to be characterized throughout the spring or fall migratory stages. Additionally, we examined flexible patterns of muscle, body mass, and fat score in migrant white-crowned sparrows (Zonotrichia leucophrys gambelii) in comparison with those in a resident subspecies (Zonotrichia leucophrys nuttalli) during the stages they share to evaluate the influence of different life histories. Migrants showed hypertrophy of the pectoralis muscle fiber area on the wintering grounds in late prealternate molt, yet increased pectoralis muscle mass was not detected until birds readied for spring departure. While pectoralis profile and fat scores enlarged at predeparture in spring and fall, pectoralis, cardiac, and body masses were greater only in spring stages, suggesting seasonal differences for migratory preparation. Gastrocnemius mass showed little change throughout all stages, whereas gastrocnemius fiber area declined steadily but rebounded in fall on the wintering grounds, where migrants become more sedentary. In general, residents are heavier birds with larger leg structures, while migrants sport longer wings and greater heart mass. Phenotypic flexibility was most prominent among residents with peaks of pectoralis, gastrocnemius, and body masses during the winter stage, when local weather is most severe. Thus, the subspecies express specific patterns of phenotypic flexibility with peaks coinciding with the stages of heightened energy demands: the winter stage for residents and the spring stages for migrants.

Anadromous trout from opposite sides of the globe: biology, ocean ecology, and management of anadromous brown and cutthroat trout

Anadromous brown trout (Salmo trutta) in the northeastern Atlantic Ocean, and coastal cutthroat trout (Oncorhynchus clarkii clarkii) in the northeastern Pacific Ocean, are analogs in many ways. Both species display similar patterns of complex life histories and behavioral flexibility, are iteroparous and facultatively anadromous and occupy nearshore coastal marine habitats where numerous populations often mix. These characteristics create specific challenges for management and conservation that have been complicated by inadequate scientific attention in some areas. Both species are declining across their native range, and their ecology make them particularly vulnerable to habitat destruction, fishing, and climate change. Here, we review the available literature to compare the biology, ocean ecology, and management practices of these two species. We highlight ecological similarities and differences between the species and identify current knowledge gaps suggesting future research needs and management actions. Using a comparative approach, the review aims to promote and facilitate knowledge exchange between anadromous trout research communities from opposite sides of the globe to improve management and conservation of these species and stimulate the production of management plans specific to anadromous trout.

MUSIC CREATIVITY INTERVENTION FOR OLDER ADULTS WITH AND WITHOUT MCI: COGNITIVE BENEFITS AND NEURAL MECHANISMS

Abstract Alzheimer’s and related dementias are debilitating conditions, and at this time, no cure has been identified. Older age is associated with cognitive decline and dementia. Developing and testing innovative non-pharmacological interventions to delay the loss of functional ability and understand the neurobiological mechanisms underlying the intervention’s efficacy is imperative. We conducted a semi-randomized clinical trial evaluating the effects of a novel music creativity curriculum on cognitive and neurological outcomes. Eighty older adults with and without a mild cognitive impairment (MCI) diagnosis were randomized to a 6-week music creativity intervention or a 6-week no-treatment control condition. Before and after the six weeks, both groups participated in a series of self-report and cognitive assessments; they also participated in resting-state fMRI scans to quantify whole-brain network patterns of modularity and flexibility. Those randomized to the music group exhibited improved overall cognitive function and working memory relative to the control group (assessed using standard clinical neuropsychological assessments). The association between being randomized to the music group and increased cognitive function was more robust among those who exhibited greater neural flexibility at baseline. The study shows that music creativity interventions may positively affect cognition, especially among those whose neural network structure is more dynamic or flexible. This study is innovative as it is among the first to identify possible neural mechanisms underlying why music creativity interventions confer a more significant cognitive benefit for some older adults than others.

Sequence-Dependent Properties of the RNA Duplex.

Sequence-dependent properties of the DNA duplex have been accurately described using extensive molecular dynamics simulations. The RNA duplex meanwhile─which is typically represented as a sequence-averaged rigid rod─does not benefit from having equivalent molecular dynamics simulations. In this paper, we present a massive simulation effort using a set of ABC-optimized duplexes from which we derived tetramer-resolution properties of the RNA duplex and a simple mesoscopic model that can represent elastic properties of long RNA duplexes. Despite the extreme chemical similarity between DNA and RNA, the local and global elastic properties of the duplexes are very different. DNA duplexes show a complex and nonelastic pattern of flexibility, for instance, while RNA duplexes behave as an elastic system whose deformations can be represented by simple harmonic potentials. In RNA duplexes (RNA2), not only are intra- and interbase pair parameters (equilibrium and mechanical) different from those in the equivalent DNA duplex sequences (DNA2) but the correlations between movements also differ. Simple statements on the relative flexibility or stability of both polymers are meaningless and should be substituted by a more detailed description depending on the sequence and the type of deformation considered.

Identity affirmation is associated with adaptive cardiovascular flexibility in response to stress among sexual and gender minority people of color

BackgroundResearch with sexual and gender minority (e.g., lesbian, gay, bisexual, queer, asexual, trans, non-binary) people of Color (SGM-PoC) has largely focused on risk and negative health outcomes. The existing strengths-based mental health research suggests that identity affirmation may be associated with psychological resilience and good mental health among SGM-PoC, but little is known about predictors of physiological resilience and biomarkers of physical health in this population. Adaptive cardiovascular flexibility is an indicator of physiological resilience and physical health in that it enables the body to mobilize resources to adapt to challenges. This study explored the association between identity affirmation and physiological resilience, observed through cardiovascular flexibility in response to stress among SGM-PoC. MethodsParticipants were 95 SGM-PoC of varying ethnoracial backgrounds, sexual orientations, and gender identities, residing in Canada. Participants completed questionnaires on sociodemographic and psychosocial variables, including a measure of identity affirmation, the Queer People of Color Identity Affirmation Scale (QPIAS). In a laboratory setting, we induced stress using the Trier Social Stress Test and measured heart rate variability (HRV) over time using wearable electrocardiogram devices. ResultsResults from multilevel modeling analyses revealed that high QPIAS scores were associated with adaptive cardiovascular flexibility, as evidenced by reduced HRV during stress exposure, followed by HRV increase during recovery. As QPIAS scores increased, the shape of HRV trajectory increasingly reflected our predicted pattern of adaptive cardiovascular flexibility. Meanwhile, low QPIAS scores were not associated with this pattern and appeared to predict a more flatlined HRV activity during the experiment. ConclusionsFindings indicate that Queer People of Color identity affirmation may be related to physiological resilience, observed through a more adaptive cardiovascular profile when responding to stress. Identity affirmation may thus be a protective factor for SGM-PoC, pointing to the critical importance of affirming resources and strengths-based health research.

In silico design, synthesis and anti-HIV activity of quinoline derivatives as non-nucleoside reverse transcriptase inhibitors (NNRTIs)

A series of quinoline derivatives has been designed, synthesized and screened for their anti-HIV properties. The drug-like properties of compounds were evaluated first and then molecular docking using DS v20.1.0.19295 software showed that the compounds behaved as non-nucleoside reverse transcriptase inhibitors (NNRTIs) while interacting at the allosteric site of target HIV-RT protein (PDB:3MEC). The docking results revealed that all compounds formed hydrogen bonds with Lys101, Lys103, Val179, Tyr188, Gln190, Gly190, Pro225, Phe227, and Tyr318, and showed π-interaction with Tyr188 and Tyr318. TOPKAT (Toxicity Prediction by Komputer Assisted Technology) results confirmed that the compounds were found to be less toxic than the reference drugs. Density functional theory (DFT) analysis was performed to assess the binding affinity of all compounds. Further, molecular dynamics (MD) simulations were performed on compound 6 and delavirdine with HIV-RT enzyme. Comprehensive MD analyses showed a similar pattern of conformational stability and flexibility in both the complexes suggesting alike inhibitory action. The hydrogen-bonding interactions and the binding energy of active-site residues for the compound 6 complex revealed strong inhibitory activity than the reference (delavirdine) complex. Thus, the compound 6 might act as a potential inhibitor against HIV-RT. Overall, this study revealed that compound 6 (5-hydroxy-N-(4-methyl-2-oxo-1,2-dihydroquinolin-8-yl) thiophene-2-sulfonamide) has prudent anti-HIV activity against both HIV-1 (SI = 2.65) and HIV-2 (SI = 2.32) that can further be utilised in drug discovery against HIV virus.

Low-intensity blast induces acute glutamatergic hyperexcitability in mouse hippocampus leading to long-term learning deficits and altered expression of proteins involved in synaptic plasticity and serine protease inhibitors

Neurocognitive consequences of blast-induced traumatic brain injury (bTBI) pose significant concerns for military service members and veterans with the majority of “invisible injury.” However, the underlying mechanism of such mild bTBI by low-intensity blast (LIB) exposure for long-term cognitive and mental deficits remains elusive. Our previous studies have shown that mice exposed to LIB result in nanoscale ultrastructural abnormalities in the absence of gross or apparent cellular damage in the brain. Here we tested the hypothesis that glutamatergic hyperexcitability may contribute to long-term learning deficits. Using brain slice electrophysiological recordings, we found an increase in averaged frequencies with a burst pattern of miniature excitatory postsynaptic currents (mEPSCs) in hippocampal CA3 neurons in LIB-exposed mice at 1- and 7-days post injury, which was blocked by a specific NMDA receptor antagonist AP5. In addition, cognitive function assessed at 3-months post LIB exposure by automated home-cage monitoring showed deficits in dynamic patterns of discrimination learning and cognitive flexibility in LIB-exposed mice. Collected hippocampal tissue was further processed for quantitative global-proteomic analysis. Advanced data-independent acquisition for quantitative tandem mass spectrometry analysis identified altered expression of proteins involved in synaptic plasticity and serine protease inhibitors in LIB-exposed mice. Some were correlated with the ability of discrimination learning and cognitive flexibility. These findings show that acute glutamatergic hyperexcitability in the hippocampus induced by LIB may contribute to long-term cognitive dysfunction and protein alterations. Studies using this military-relevant mouse model of mild bTBI provide valuable insights into developing a potential therapeutic strategy to ameliorate hyperexcitability-modulated LIB injuries.

Phenotypic plasticity in the energy metabolism of a small Andean rodent: Effect of short-term thermal acclimation and developmental conditions.

The study of phenotypic variation within species in response to different environments is a central issue in evolutionary and ecological physiology. Particularly, ambient temperature is one of the most important factors modulating interactions between animals and their environment. Phyllotis xanthopygus, a small Andean rodent, exhibits intraspecific differences along an altitudinal gradient in traits relevant to energy balance that persist after acclimation to common experimental temperatures. Therefore, we aim to explore geographic variations in energetic traits of P. xanthopygus and to assess the contribution of phenotypic plasticity to population differences. We compared metabolic rate and thermal conductance in response to different acclimation temperatures in animals collected at distinct altitudes (F0 generation) and in their offspring, born and raised under common-garden conditions (F1 generation). We found intraspecific differences in resting metabolic rate (RMR) of animals collected at different altitudes that were no longer evident in the F1 generation. Furthermore, although both generations showed the same pattern of RMR flexibility in response to acclimation temperature, its magnitude was lower for the F1 individuals. This suggests that developmental conditions affect the short-term acclimation capacity of this trait during adulthood. On the other hand, thermal conductance (C) showed irreversible plasticity, as animals raised in the laboratory at stable warm conditions had a relatively higher C than the animals from the field, showing no adjustments to thermal acclimation during adulthood in either group. In sum, our results support the hypothesis that the developmental environment shapes energetic traits, emphasizing the relevance of incorporating ontogeny in physiological studies.

Genetic Variability of the Functional Domains of Chromodomains Helicase DNA-Binding (CHD) Proteins.

In the past few years, there has been an increasing neuroscientific interest in understanding the function of mammalian chromodomains helicase DNA-binding (CHD) proteins due to their association with severe developmental syndromes. Mammalian CHDs include nine members (CHD1 to CHD9), grouped into subfamilies according to the presence of specific functional domains, generally highly conserved in evolutionary terms. Mutations affecting these domains hold great potential to disrupt protein function, leading to meaningful pathogenic scenarios, such as embryonic defects incompatible with life. Here, we analysed the evolution of CHD proteins by performing a comparative study of the functional domains of CHD proteins between orthologous and paralogous protein sequences. Our findings show that the highest degree of inter-species conservation was observed at Group II (CHD3, CHD4, and CHD5) and that most of the pathological variations documented in humans involve amino acid residues that are conserved not only between species but also between paralogs. The parallel analysis of both orthologous and paralogous proteins, in cases where gene duplications have occurred, provided extra information showing patterns of flexibility as well as interchangeability between amino acid positions. This added complexity needs to be considered when the impact of novel mutations is assessed in terms of evolutionary conservation.

The Application of Flexibility Concept on East Java’s Art Auditorium

East Java art has a diversity of types and forms of performances. There are types of performances in the form of theatrical and ballet performances. This traditional art performance is intended to convey messages, advice, and past stories. This presentation is presented with various types of art so that between the types of theatrical or dance performances, each has a variety of needs for its stage and capacity. However, the lack of staging facilities is one of the problems that result in reduced artistic activities, so that some traditional arts in East Java are threatened with extinction. In this study, the purpose of this study is to look for patterns of flexibility in the auditorium to meet the needs of East Java art activities. The method used is the observation method. The observation was carried out by observing each type of East Java art activities to be accommodated, namely the type of traditional dance and theater. The selected arts are several art representatives who have the same type of performance. From the results of data analysis it can be concluded that the auditorium can at least adapt to 4 types of spatial configurations: arena, endstage, proscenium, and plaind stage.

To Be or Not to Be Flexible: Selective impairments as a means to differentiate between depression and PTSD symptoms

During the course of their lives, most individuals experience at least one potentially traumatic event. For some individuals this experience may result in them developing depression and/or post-traumatic stress disorder (PTSD) symptoms. The aim of the present study was to test the interactive effect of traumatic exposure and impaired cognitive flexibility on the tendency to develop either depression or PTSD symptoms. Eighty-two college students (M age = 25.32, SD age = 4.09) were assessed for exposure to traumatic events, depressive and PTSD symptoms. In addition, they completed a performance-based learning paradigm to evaluate the unique patterns of cognitive flexibility, defined as reduced and enhanced updating of prior knowledge in the face of new information. We predicted and found that for individuals with reduced updating, greater exposure to trauma was associated with elevated depressive symptoms. Contrary to our prediction, for individuals with enhanced updating, greater exposure was associated with elevated PTSD symptoms. While cognitive flexibility is traditionally associated with adaptive outcomes, our results illuminate the important role of a delicate updating balance to adaptively cope with aversive life events. The findings highlight the possible different roles of cognitive flexibility in the development of psychopathology and may serve as a first step toward developing tailored prevention and treatment methods.

Understanding the parent-child coregulation patterns shaping child self-regulation.

Parent-child coregulation, thought to support children's burgeoning regulatory capacities, is the process by which parents and their children regulate one another through their goal-oriented behavior and expressed affect. Two particular coregulation patterns-dyadic contingency and dyadic flexibility-appear beneficial in early childhood, but their role in the typical development of self-regulation is not yet clear. The present study examined whether dynamic parent-child patterns of dyadic contingency and dyadic flexibility in both affect and goal-oriented behavior (e.g., discipline, compliance) predicted multiple components of preschoolers' self-regulation. Mother-child dyads (N = 100) completed structured and unstructured dyadic tasks in the laboratory at age 3, and mothers completed child self-regulation measures at age 4. Findings showed that more flexible and contingent affective parent-child processes, as long as the affective content was primarily positive or neutral, predicted higher levels of self-regulation in early childhood. However, when dyads engaged in more negative affective and behavioral content, higher levels of affective and behavioral contingency and behavioral flexibility predicted lower levels of child self-regulation. Findings suggest parent-child coregulation processes play a meaningful role in children's typical regulatory development and that parent-child coregulation patterns can be potentially adaptive or maladaptive for child outcomes depending on the content of the interaction. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Evolutionary Potential and Morphological Integration of the Shoulder Girdle Among Primates

The morphology of the shoulder girdle is highly varied among primates, possibly reflecting an array of functional demands placed through the range of locomotor and behavioral movements exercised in the upper limb. Variation in the shoulder girdle, and especially the scapula, is hypothesized to be the result of directional selection for different functional demands. Evolutionary analyses of the shoulder girdle often assess this anatomical region and its traits individually, which implicitly models the evolution of the girdle as independent of other traits. However, the primate shoulder girdle has developmental and functional covariances with the basicranium, pelvis, humerus, and vertebral column that we have recently demonstrated have potential to influence its evolution through correlated responses to directional selection. Whether these relationships are similar across primate taxa and how these relationships may affect morphological variation among primates is unknown.Here we evaluate the strength of the covariance and evolutionary potential among four anatomical regions: shoulder girdle, basicranium, pelvis, and humerus. We obtained cranial and postcranial linear dimensions from Alouatta, Colobus, Homo, Hylobates, and Papio. Measurements were mean standardized prior to analysis. We estimated morphological integration using Wagner's variance of the eigenvalues (VE), and estimated evolutionary potential using Hansen and Houle's evolutionary flexibility (EF) with 1000 simulated random selection gradients. EF captures how closely the evolutionary response in a group of traits follows the direction of the selection. We evaluated differences in VE and EF among taxa by performing a pairwise comparison of the bootstrapped values for each. Analyses were performed using the R statistical environment.Our results show that patterns of morphological integration and evolutionary flexibility among anatomical regions differ across primate taxa, with humans having the greatest evolutionary potential and Papio the lowest. Broadly, the patterns revealed among taxa do not strictly correspond to the functional demands of the upper limb experienced by each; taxa with different locomotor demands on the upper limb have the same kinds of covariance or evolutionary flexibility. Thus, evolutionary hypotheses of primate shoulder girdle morphological variation that evaluate functional demands alone may not account for the effect of these relationships. We conclude that different trait covariances among anatomical regions may manifest as morphological differences in the primate shoulder girdle, which has important implications for models of shoulder evolution.Support or Funding InformationThis research is supported by a National Science Foundation Doctoral Dissertation Improvement Grant (NSF BCS‐1825995).

Segmental Flexibility in Adolescent Idiopathic Scoliosis Assessed Using the Fulcrum-bending Radiography Method.

Assessment of segmental flexibility at each disk level of the scoliotic curve in patients with adolescent idiopathic scoliosis (AIS) has rarely been performed, despite its importance for surgical planning of fusion levels. The fulcrum-bending radiography method could be used to assess flexibility at specific spinal segments of the scoliotic curve for preoperative planning. Therefore, our aim was to use the fulcrum-bending method to evaluate the pattern of segmental flexibility in patients with AIS. Our retrospective analysis was based on preoperative fulcrum-bending radiographs in 21 patients presenting with main thoracic curve scoliosis. The apex vertebra was defined as the "0" level, with the sequential cranial disk levels defined as "+1 to +5" and the sequential caudal levels as "-1 to -5." The segmental Cobb angle was measured on both, standing and fulcrum-bending radiographs. The segmental flexibility index (FI) was calculated as: [(the segmental Cobb angle in standing position-the segmental Cobb angle in the fulcrum-bending position)/the segmental Cobb angle in standing position]×100. The FI was measured from the upper-most to the lower-most end vertebrae of the main curve. There was a significant difference in the FI among segments, with the greatest flexibility detected at the level of the -5 disk (median FI, 50%) and least flexibility at the periapical segments (+1 and -1; FI, 50%-66.7%). The curve around the apex and upper thoracic segments in thoracic AIS is relatively rigid. Understanding differences in FI between each disk level is important for optimal corrective surgery.

Machine Learning to Identify Flexibility Signatures of Class A GPCR Inhibition.

We show that machine learning can pinpoint features distinguishing inactive from active states in proteins, in particular identifying key ligand binding site flexibility transitions in GPCRs that are triggered by biologically active ligands. Our analysis was performed on the helical segments and loops in 18 inactive and 9 active class A G protein-coupled receptors (GPCRs). These three-dimensional (3D) structures were determined in complex with ligands. However, considering the flexible versus rigid state identified by graph-theoretic ProFlex rigidity analysis for each helix and loop segment with the ligand removed, followed by feature selection and k-nearest neighbor classification, was sufficient to identify four segments surrounding the ligand binding site whose flexibility/rigidity accurately predicts whether a GPCR is in an active or inactive state. GPCRs bound to inhibitors were similar in their pattern of flexible versus rigid regions, whereas agonist-bound GPCRs were more flexible and diverse. This new ligand-proximal flexibility signature of GPCR activity was identified without knowledge of the ligand binding mode or previously defined switch regions, while being adjacent to the known transmission switch. Following this proof of concept, the ProFlex flexibility analysis coupled with pattern recognition and activity classification may be useful for predicting whether newly designed ligands behave as activators or inhibitors in protein families in general, based on the pattern of flexibility they induce in the protein.

From the Citizen’s Constitution to REDD+

This article identifies forest and climate change public policy instruments in Brazil. The country created a complex network of forest protection, deforestation control policies and Measurement, Reporting and Verification (MRV) instruments, culminating with institutional arrangements for Reducing Emissions from Deforestation and Forest Degradation (REDD+). Brazil’s positions at the United Nations Framework Convention on Climate Change (UNFCCC) negotiations relied on a diverse pattern of leadership, blockage, and flexibility. Under the Warsaw REDD+ Framework, Brazil reduced 8,2 billion tons of CO2 equivalent (tCO2e) and received almost 1,4 billion American dollars as results-based payments, by the end of 2018.