Global Structural Changes Research Articles

Local Disordering in the Amorphous Network of a Solution-Processed Indium Tin Oxide Thin Film.

The polyhedra unit structure (MOx) in an amorphous metal oxide network has more freedom and flexibility than the same unit structure in a crystalline phase. Consequently, a mild external stimulus (e.g., instant photonic and acoustic energy) could affect and change this network parameter, thereby enhancing and modulating the electrical properties. However, it is difficult to tune these atomic parameters solely while maintaining the metal oxide's initial global amorphous phase and thereby preventing mechanical instability at the film-substrate interface (i.e., cracking or distortion). Here, we report local disordering in an amorphous network of a solution-processable indium tin oxide (ITO) film, where the disordering is triggered by mild-light irradiation (<0.1 mJ/cm2). Through a combination of systematic characterizations of the global structural and chemical compositional changes in conjunction with extended X-ray absorption fine structure analyses, we revealed the distortion of the atomic structure in the amorphous network of the ITO film led to the formation of additional structural oxygen vacancies. Our findings enabled us to fabricate mechanical-instability-free, perfect amorphous-phase ITO thin films on plastic substrates, where the sheet resistance substantially decreased to ∼ 2 × 103 Ω/□. Furthermore, this sheet resistance did not vary when the film and substrate were bent to a radius of 2 mm and could operate at low temperatures. This work can pave the novel way to fabricate high-quality flexible transparent electrodes suitable for rapid, cost-effective, and patternable processing on plastic substrates, and the domain can be extended to flexible electronics.

Alzheimer's Disease Diagnosis With Brain Structural MRI Using Multiview-Slice Attention and 3D Convolution Neural Network.

Numerous artificial intelligence (AI) based approaches have been proposed for automatic Alzheimer's disease (AD) prediction with brain structural magnetic resonance imaging (sMRI). Previous studies extract features from the whole brain or individual slices separately, ignoring the properties of multi-view slices and feature complementarity. For this reason, we present a novel AD diagnosis model based on the multiview-slice attention and 3D convolution neural network (3D-CNN). Specifically, we begin by extracting the local slice-level characteristic in various dimensions using multiple sub-networks. Then we proposed a slice-level attention mechanism to emphasize specific 2D-slices to exclude the redundancy features. After that, a 3D-CNN was employed to capture the global subject-level structural changes. Finally, all these 2D and 3D features were fused to obtain more discriminative representations. We conduct the experiments on 1,451 subjects from ADNI-1 and ADNI-2 datasets. Experimental results showed the superiority of our model over the state-of-the-art approaches regarding dementia classification. Specifically, our model achieves accuracy values of 91.1 and 80.1% on ADNI-1 for AD diagnosis and mild cognitive impairment (MCI) convention prediction, respectively.

The Molecular Basis and Pathophysiology of Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a complex orofacial pain syndrome characterized by the paroxysmal onset of pain attacks in the trigeminal distribution. The underlying mechanism for this debilitating condition is still not clearly understood. Decades of basic and clinical evidence support the demyelination hypothesis, where demyelination along the trigeminal afferent pathway is a major driver for TN pathogenesis and pathophysiology. Such pathological demyelination can be triggered by physical compression of the trigeminal ganglion or another primary demyelinating disease, such as multiple sclerosis. Further examination of TN patients and animal models has revealed significant molecular changes, channelopathies, and electrophysiological abnormalities in the affected trigeminal nerve. Interestingly, recent electrophysiological recordings and advanced functional neuroimaging data have shed new light on the global structural changes and the altered connectivity in the central pain-related circuits in TN patients. The current article aims to review the latest findings on the pathophysiology of TN and cross-examining them with the current surgical and pharmacologic management for TN patients. Understanding the underlying biology of TN could help scientists and clinicians to identify novel targets and improve treatments for this complex, debilitating disease.

Global socio-economic and climate change mitigation scenarios through the lens of structural change

This paper analyses structural change in the economy as a key but largely unexplored aspect of global socio-economic and climate change mitigation scenarios. Structural change can actually drive energy and land use as much as economic growth and influence mitigation opportunities and barriers. Conversely, stringent climate policy is bound to induce specific structural and socio-economic transformations that are still insufficiently understood. We introduce Multi-Sectoral macroeconomic Integrated Assessment Models as tools to capture the key drivers of structural change and we conduct a multi-model study to assess main structural effects – changes of the sectoral composition and intensity of trade of global and regional economies – in a baseline and 2°C policy scenario by 2050. First, the range of baseline projections across models, for which we identify the main drivers, illustrates the uncertainty on future economic pathways – in emerging economies especially – and inform on plausible alternative futures with implications for energy use and emissions. Second, in all models, climate policy in the 2°C scenario imposes only a second-order impact on the economic structure at the macro-sectoral level – agriculture, manufacturing and services - compared to changes modelled in the baseline. However, this hides more radical changes for individual industries – within the energy sector especially. The study, which adopts a top-down framing of global structural change, represents a starting point to kick-start a conversation and propose a new research agenda seeking to improve understanding of the structural change effects in socio-economic and mitigation scenarios, and better inform policy assessments.

Assessing the effect of a regional integrated care model over ten years using quality indicators based on claims data \u2013 the basic statistical methodology of the INTEGRAL project

BackgroundThe regional integrated health care model “Healthy Kinzigtal” started in 2006 with the goal of optimizing health care and economic efficiency. The INTEGRAL project aimed at evaluating the effect of this model on the quality of care over the first 10 years.MethodsThis methodological protocol supplements the study protocol and the main publication of the project. Comparing quality indicators based on claims data between the intervention region and 13 structurally similar control regions constitutes the basic scientific approach. Methodological key issues in performing such a comparison are identified and solutions are presented.ResultsA key step in the analysis is the assessment of a potential trend in prevalence for a single quality indicator over time in the intervention region compared to the corresponding trends in the control regions. This step has to take into account that there may be a common - not necessarily linear - trend in the indicator over time and that trends can also appear by chance. Conceptual and statistical approaches were developed to handle this key step and to assess in addition the overall evidence for an intervention effect across all indicators. The methodology can be extended in several directions of interest.ConclusionsWe believe that our approach can handle the major statistical challenges: population differences are addressed by standardization; we offer transparency with respect to the derivation of the key figures; global time trends and structural changes do not invalidate the analyses; the regional variation in time trends is taken into account. Overall, the project demanded substantial efforts to ensure adequateness, validity and transparency.

The spatial dissemination of COVID-19 and associated socio-economic consequences.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has wreaked havoc worldwide with millions of lives claimed, human travel restricted and economic development halted. Leveraging city-level mobility and case data, our analysis shows that the spatial dissemination of COVID-19 can be well explained by a local diffusion process in the mobility network rather than a global diffusion process, indicating the effectiveness of the implemented disease prevention and control measures. Based on the constructed case prediction model, it is estimated that there could be distinct social consequences if the COVID-19 outbreak happened in different areas. During the epidemic control period, human mobility experienced substantial reductions and the mobility network underwent remarkable local and global structural changes toward containing the spread of COVID-19. Our work has important implications for the mitigation of disease and the evaluation of the socio-economic consequences of COVID-19 on society.

Tracking local and global structural changes in a protein by cold ion spectroscopy.

Characterization of native structures of proteins in the gas phase remains challenging due to the unpredictable conformational changes the molecules undergo during desolvation and ionization. We spectroscopically studied cryogenically cooled protonated protein ubiquitin and its microhydrated complexes prepared in the gas phase in a range of charge states under different ionization conditions. The UV spectra appear vibrationally resolved for the unfolded protein, but become redshifted and smooth for the native-like structures of ubiquitin. This spectroscopic change results from the H-bonding of the hydroxyl of Tyr to the amide group of Glu-51 in the compact structures; the minimum length of this bond was estimated to be ∼1.7 Å. IR spectroscopy reflects the global structural change by observing redshifts of free NH/OH-stretch vibrational transitions. Evaporative cooling of microhydrated complexes of ubiquitin keeps the protein chilly during ionization, enabling native-like conformers with up to eight protons to survive in the gas phase.

От третьей промышленной революции — к четвертой (сравнительный обзор концепций)

The article describes the evolution of the theoretical concept of industrial transformation in the era of modern economic growth. Analysis of contemporary research literature brings to light the key perspectives on the role of industry in sustainable development and the influence of industrial changes on the global business cycles. Special emphasis is made on the concepts of third and fourth industrial revolutions in Russian and international research and the associated concepts such as “technological change”, “technological revolution”, and “innovation”. Among other things, the study discusses the difference between the Schumpeterian interpretation of long waves of economic growth and the concept of sequential change of techno-economic paradigms proposed by Carlota Perez. The conclusion is made that although economists may disagree about the sources and features of technological transformations as well as the problems they engender, the role of technology is generally seen as crucial to global structural changes. Regarding the Russian context, it is shown that as the centre of the global economy is shifting to the East, it is essential that the country’s government should stop fetishizing particular spheres of technological progress.

Промышленная политика Евразийского экономического союза

The necessity to establish a consistent and sensibly planned industrial policy at the level of regional integration associations (RIAs) is justified in terms of the modern global structural changes as well as due to the growing number of protectionist measures applied by particular states and regional integration associations regarding the field of imported industrial goods (e.g., the EU carbon tax, trade wars, and restrictions due to economic sanctions). Despite the fact that both Russian and foreign literature pay full attention to the State industrial policy shaping and implementation issues, although, the conceptual theoretical grounds of the industrial policy shaping and implementation within RIAs are missing and are poorly researched. Based on the review of theoretical knowledges article proposes a conceptual approach to the RIAs industrial policy implementation in the context of the State industrial policy shaping. The article identifies features and restrictions hampering implementation process as well as determines proper conceptual definition of specific terms. For instance, the RIAs industrial policy consists of the complex of regulatory instruments at supranational level which have both stimulating and coordinating nature as well as national regulatory system with the aim of harmonizing the development of member countries’ industrial capacities, with the involvement of supranational institutions. Also, it is to be noted that the main feature of the RIAs industrial policy is its coordinating and stimulating nature. Using the example of Eurasian Economic Union (hereinafter, the EAEU) the approach to its industrial policy development has been developed. Based on the analysis of particular macroeconomic indicators of the EAEU Member States, their industrial development priorities, comparison of those priorities with the global trends, the following EAEU industrial strategic priorities have been identified: assisting in promotion of commodities to foreign markets, encouraging innovation activities, increasing investment attractiveness, developing small- and medium-sized businesses, environment protection, and digital transformation. The general development trajectories of industrial development which has been highlighted in the article as well as the proposed coordinating and stimulating supranational regulation measures can be a solid fundament for achieving development objectives of the EAEU Member States and play a catalyst role in transforming their economies.

ENSURING A BALANCED INNOVATIVE DEVELOPMENT OF UKRAINE'S ECONOMY UNDER THE CONDITIONS OF GLOBAL UNCERTAINTY

The need to ensure balanced innovative development of Ukraine is due to global uncertainty, dynamic processes and structural changes that are taking place today in the global economy. In these conditions, it is relevant to determine the position of Ukraine in the global coordinate system precisely in terms of innovation. Assessment of the state of the scientific and technical sphere, innovative development, research results in the countries of the world at the international level is carried out according to many indicators of various ratings, the most authoritative of which are: Global Innovation Index, Global Competitiveness Index, European Innovation Scoreboard. An analysis of the achieved level of innovative development of the Ukrainian economy in terms of international ratings requires the determination of methodological principles for their calculation. According to the results of the study, it was found that, despite some positive trends, in general, there is a significant gap between the level of innovative development of Ukraine and developed countries. It was found that the position of our country on the Global Competitiveness Index in the past few years has fluctuated between 76-89 places, in accordance with which, it is concluded that there are no effective reforms in the field of research, technology and innovation. The study of innovative activities of European countries and countries - regional neighbors demonstrated Ukraine's membership in the group with the status of «Modest Innovator». Low values of the analyzed indicators in international ratings are associated with errors in government policy and existing problems in the innovation sphere - the use of human potential, the quality of innovation infrastructure, the formation of sustainable relationships between elements of the national innovation system as a whole. The issues of cooperation with international institutions and poor integration into international scientific, technical and innovative cooperation remain unresolved. In this regard, steps are proposed in the direction of Ukraine joining the global innovation processes, which will bring the rating results closer to the level of developed countries in the future.

Epigenome-wide association study of global cortical volumes in generation Scotland: Scottish family health study

ABSTRACT A complex interplay of genetic and environmental risk factors influence global brain structural alterations associated with brain health and disease. Epigenome-wide association studies (EWAS) of global brain imaging phenotypes have the potential to reveal the mechanisms of brain health and disease and can lead to better predictive analytics through the development of risk scores. We perform an EWAS of global brain volumes in Generation Scotland using peripherally measured whole blood DNA methylation (DNAm) from two assessments, (i) at baseline recruitment, ~6 years prior to MRI assessment (N = 672) and (ii) concurrent with MRI assessment (N=565). Four CpGs at baseline were associated with global cerebral white matter, total grey matter, and whole-brain volume (Bonferroni p≤7.41×10−8, βrange = −1.46x10−6 to 9.59 × 10−7). These CpGs were annotated to genes implicated in brain-related traits, including psychiatric disorders, development, and ageing. We did not find significant associations in the meta-analysis of the EWAS of the two sets concurrent with imaging at the corrected level. These findings reveal global brain structural changes associated with DNAm measured ~6 years previously, indicating a potential role of early DNAm modifications in brain structure. Although concurrent DNAm was not associated with global brain structure, the nominally significant findings identified here present a rationale for future investigation of associations between DNA methylation and structural brain phenotypes in larger population-based samples.

HIV-1 integrase binding to genomic RNA 5\u2032-UTR induces local structural changes in vitro and in virio

BackgroundDuring HIV-1 maturation, Gag and Gag-Pol polyproteins are proteolytically cleaved and the capsid protein polymerizes to form the honeycomb capsid lattice. HIV-1 integrase (IN) binds the viral genomic RNA (gRNA) and impairment of IN-gRNA binding leads to mis-localization of the nucleocapsid protein (NC)-condensed viral ribonucleoprotein complex outside the capsid core. IN and NC were previously demonstrated to bind to the gRNA in an orthogonal manner in virio; however, the effect of IN binding alone or simultaneous binding of both proteins on gRNA structure is not yet well understood.ResultsUsing crosslinking-coupled selective 2′-hydroxyl acylation analyzed by primer extension (XL-SHAPE), we characterized the interaction of IN and NC with the HIV-1 gRNA 5′-untranslated region (5′-UTR). NC preferentially bound to the packaging signal (Psi) and a UG-rich region in U5, irrespective of the presence of IN. IN alone also bound to Psi but pre-incubation with NC largely abolished this interaction. In contrast, IN specifically bound to and affected the nucleotide (nt) dynamics of the apical loop of the transactivation response element (TAR) and the polyA hairpin even in the presence of NC. SHAPE probing of the 5′-UTR RNA in virions produced from allosteric IN inhibitor (ALLINI)-treated cells revealed that while the global secondary structure of the 5′-UTR remained unaltered, the inhibitor treatment induced local reactivity differences, including changes in the apical loop of TAR that are consistent with the in vitro results.ConclusionsOverall, the binding interactions of NC and IN with the 5′-UTR are largely orthogonal in vitro. This study, together with previous probing experiments, suggests that IN and NC binding in vitro and in virio lead to only local structural changes in the regions of the 5′-UTR probed here. Accordingly, disruption of IN-gRNA binding by ALLINI treatment results in local rather than global secondary structure changes of the 5′-UTR in eccentric virus particles.Graphical

Monitoring Dynamics, Structure, and Magnetism of Switchable Metal-Organic Frameworks via 1 H-Detected MAS NMR.

We present a toolbox for the rapid characterisation of powdered samples of paramagnetic metal–organic frameworks at natural abundance by 1H‐detected solid‐state NMR. Very fast MAS rates at room and cryogenic temperatures and a set of tailored radiofrequency irradiation schemes help overcome the sensitivity and resolution limits often associated with the characterisation of MOF materials. We demonstrate the approach on DUT‐8(Ni), a framework containing Ni2+ paddle‐wheel units which can exist in two markedly different architectures. Resolved 1H and 13C resonances of organic linkers are detected and assigned in few hours with only 1–2 mg of sample at natural isotopic abundance, and used to rapidly extract information on structure and local internal dynamics of the assemblies, as well as to elucidate the metal electronic properties over an extended temperature range. The experiments disclose new possibilities for describing local and global structural changes and correlating them to electronic and magnetic properties of the assemblies.

Novel Role of Gestational Hydralazine in Limiting Maternal and Dietary Obesity-Related Chronic Kidney Disease.

BackgroundMaternal obesity is a risk factor for chronic kidney disease (CKD) in offspring, underpinning the theory of the developmental origins of health and disease. DNA methylation has been implicated in the programming of adult chronic disease by maternal obesity, therefore, DNA demethylating agents may mitigate offspring risk of disease. In rodent models, low-dose hydralazine has previously been shown to reduce renal fibrosis via DNA demethylation. We used mouse models of maternal obesity and offspring obesity to determine whether administration of low-dose hydralazine during gestation can prevent fetal programming of CKD in offspring.MethodsFemale C57BL/6 mice received high fat diet (HFD) or chow prior to mating, during gestation and lactation. During gestation, dams received subcutaneous hydralazine (5 mg/kg) or saline thrice-weekly. Male offspring weaned to HFD or chow, which continued until endpoint at 32 weeks. Biometric and metabolic parameters, renal global DNA methylation, renal functional and structural changes, and renal markers of fibrosis, inflammation and oxidative stress were assessed at endpoint.ResultsOffspring exposed to maternal obesity or diet-induced obesity had significantly increased renal global DNA methylation, together with other adverse renal effects including albuminuria, glomerulosclerosis, renal fibrosis, and oxidative stress. Offspring exposed to gestational hydralazine had significantly reduced renal global DNA methylation. In obese offspring of obese mothers, gestational hydralazine significantly decreased albuminuria, glomerulosclerosis, and serum creatinine. Obese offspring of hydralazine-treated lean mothers displayed reduced markers of renal fibrosis and oxidative stress.ConclusionGestational hydralazine decreased renal global DNA methylation and exerted renoprotective effects in offspring. This supports a potential therapeutic effect of hydralazine in preventing maternal obesity or dietary obesity-related CKD, through an epigenetic mechanism.

Interconversion of Unexpected Thiol States Affects the Stability, Structure, and Dynamics of Antibody Engineered for Site-Specific Conjugation.

Antibody-drug conjugates have become one of the most actively developed classes of drugs in recent years. Their great potential comes from combining the strengths of large and small molecule therapeutics: the exquisite specificity of antibodies and the highly potent nature of cytotoxic compounds. More recently, the approach of engineering antibody-drug conjugate scaffolds to achieve highly controlled drug to antibody ratios has focused on substituting or inserting cysteines to facilitate site-specific conjugation. Herein, we characterize an antibody scaffold engineered with an inserted cysteine that formed an unexpected disulfide bridge during manufacture. A combination of mass spectrometry and biophysical techniques have been used to understand how the additional disulfide bridge forms, interconverts, and changes the stability and structural dynamics of the antibody intermediate. This quantitative and structurally resolved model of the local and global changes in structure and dynamics associated with the engineering and subsequent disulfide-bonded variant can assist future engineering strategies.

Digital transformation shaping structural pillars for academic entrepreneurship: A framework proposal and research agenda.

Digital technology always accelerates change, altering organisations culturally, socially and technically. These modifications are known as “digital transformation” (DT). On a much greater scale than DT, the world was changed in 2020 by the COVID-19 pandemic, which re-organised society in the way of thinking, acting, producing, consuming and creating new business. Higher Education Institutions (HEIs) were no different, since these institutions had to make changes to the student–lecturer interaction; teaching–learning, where DT had a relevant role, above all in academic entrepreneurship. Therefore, this study aims to propose a framework showing the structural pillars of the link between digital transformation (DT) and academic entrepreneurship (AC) (DT-AC Framework). This framework identifies the new patterns, methods, skills and other discoveries in aspects such as management, information systems and culture sciences. The intention is not to analyse how the COVID-19 pandemic imposed global structural changes, but because of it, lecturers and students found their DT accelerated and intensified, and so it is necessary to investigate the pillars supporting academic entrepreneurship. The results show that DT was already emerging as a basic element of academic entrepreneurship before the pandemic, but the process has speeded up. This bibliometric study indicates the structural pillars that support entrepreneurship following the Covid19 pandemic, as created from DT in universities, providing an extensive systematic review that indicates the cause and effect of the academic entrepreneurship process.

Atomistic and continuum modeling of 3D graphene honeycombs under uniaxial in-plane compression

Using large-scale molecular dynamics (MD) simulations in conjunction with continuum modeling, the deformation behaviors of three-dimensional (3D) graphene honeycomb structures under uniaxial in-plane compression have been systematically investigated. The stress-strain responses of graphene honeycombs were found to be dependent on the loading direction, prism size and lattice orientation, but little affected by the junction type. Two critical deformation events, i.e., elastic buckling and structural collapse, were identified, with the associated local and global structural changes associated at these critical events clarified. Continuum models accounting for the effect of lattice orientation and size-dependent yielding have been developed to quantitatively predict the threshold stresses for those critical deformation events. In addition, it has been demonstrated that the overall stress-strain curve of graphene honeycomb can also be reasonably well predicted via continuum modeling, albeit deviation at large strains due to effect of junction on cell wall bending. The present study provides critical mechanistic understanding and predictive tools for optimizing and designing 3D graphene honeycombs in small-scale applications.

Patz, Ronny and Goetz, Klaus H. (2019). Managing Money and Discord in the UN. Budgeting and Bureaucracy. New York, NY, USA: Oxford University Press. Hardback, 272 Seiten, ISBN: 9780198838333.

How does budgeting work for international organizations within the United Nations system? What role do states as complex principals and international bureaucracies as complex agents play within budgeting processes? By providing four case studies on the UN, ILO, UNESCO, and WHO, the authors of “Managing Money and Discord in the UN – Budgeting and Bureaucracy” offer valuable insights on budgeting and its procedures in the UN System of organizations. Their findings demonstrate that despite global financial crisis and significant structural changes in global politics, the core budget routines of international organizations have remained relatively stable over the past decades. However, with vested interests of powerful member states, complementary financial arrangements outside the core organizations, diverging intraorganizational priorities, or the rise of philanthropy and voluntary contributions, complexities for both principals and agents have increased, which ultimately put the capacity of international bureaucracies to maintain budgetary routines at risk. By bridging the gap between related, but distinct disciplines within political science, the concept of budgeting put forward in this book is equally important for the study of International Relations, International Public Administrations, Political Economy, and Public Policy.

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time.

Using spectroscopic rulers to track multiple conformations of single biomolecules and their dynamics have revolutionized the understanding of structural dynamics and its contributions to biology. While the FRET-based ruler reports on inter-dye distances in the 3-10 nm range, other spectroscopic techniques, such as protein-induced fluorescence enhancement (PIFE), report on the proximity between a dye and a protein surface in the shorter 0-3 nm range. Regardless of the method of choice, its use in measuring freely-diffusing biomolecules one at a time retrieves histograms of the experimental parameter yielding separate centrally-distributed sub-populations of biomolecules, where each sub-population represents either a single conformation that stayed unchanged within milliseconds, or multiple conformations that interconvert much faster than milliseconds, and hence an averaged-out sub-population. In single-molecule FRET, where the reported parameter in histograms is the inter-dye FRET efficiency, an intrinsically disordered protein, such as the α-Synuclein monomer in buffer, was previously reported as exhibiting a single averaged-out sub-population of multiple conformations interconverting rapidly. While these past findings depend on the 3-10 nm range of the FRET-based ruler, we sought to put this protein to the test using single-molecule PIFE, where we track the fluorescence lifetime of site-specific sCy3-labeled α-Synuclein proteins one at a time. Interestingly, using this shorter range spectroscopic proximity sensor, sCy3-labeled α-Synuclein exhibits several lifetime sub-populations with distinctly different mean lifetimes that interconvert in 10-100 ms. These results show that while α-Synuclein might be disordered globally, it nonetheless attains stable local structures. In summary, in this work we highlight the advantage of using different spectroscopic proximity sensors that track local or global structural changes one biomolecule at a time.

MolGrow: A Graph Normalizing Flow for Hierarchical Molecular Generation

We propose a hierarchical normalizing flow model for generating molecular graphs. The model produces new molecular structures from a single-node graph by recursively splitting every node into two. All operations are invertible and can be used as plug-and-play modules. The hierarchical nature of the latent codes allows for precise changes in the resulting graph: perturbations in the first layer cause global structural changes, while perturbations in the consequent layers change the resulting molecule only marginally. Proposed model outperforms existing generative graph models on the distribution learning task. We also show successful experiments on global and constrained optimization of chemical properties using latent codes of the model.