SCINE-Software for chemical interaction networks.

The software for chemical interaction networks (SCINE) project aims at pushing the frontier of quantum chemical calculations on molecular structures to a new level. While calculations on individual structures as well as on simple relations between them have become routine in chemistry, new developments have pushed the frontier in the field to high-throughput calculations. Chemical relations may be created by a search for specific molecular properties in a molecular design attempt, or they can be defined by a set of elementary reaction steps that form a chemical reaction network. The software modules of SCINE have been designed to facilitate such studies. The features of the modules are (i) general applicability of the applied methodologies ranging from electronic structure (no restriction to specific elements of the periodic table) to microkinetic modeling (with little restrictions on molecularity), full modularity so that SCINE modules can also be applied as stand-alone programs or be exchanged for external software packages that fulfill a similar purpose (to increase options for computational campaigns and to provide alternatives in case of tasks that are hard or impossible to accomplish with certain programs), (ii) high stability and autonomous operations so that control and steering by an operator are as easy as possible, and (iii) easy embedding into complex heterogeneous environments for molecular structures taken individually or in the context of a reaction network. A graphical user interface unites all modules and ensures interoperability. All components of the software have been made available as open source and free of charge.

Nanoscale chemical reaction exploration with a quantum magnifying glass.

Nanoscopic systems exhibit diverse molecular substructures by which they facilitate specific functions. Theoretical models of them, which aim at describing, understanding, and predicting these capabilities, are difficult to build. Viable quantum-classical hybrid models come with specific challenges regarding atomistic structure construction and quantum region selection. Moreover, if their dynamics are mapped onto a state-to-state mechanism such as a chemical reaction network, its exhaustive exploration will be impossible due to the combinatorial explosion of the reaction space. Here, we introduce a "quantum magnifying glass" that allows one to interactively manipulate nanoscale structures at the quantum level. The quantum magnifying glass seamlessly combines autonomous model parametrization, ultra-fast quantum mechanical calculations, and automated reaction exploration. It represents an approach to investigate complex reaction sequences in a physically consistent manner with unprecedented effortlessness in real time. We demonstrate these features for reactions in bio-macromolecules and metal-organic frameworks, diverse systems that highlight general applicability.

A human-machine interface for automatic exploration of chemical reaction networks.

Autonomous reaction network exploration algorithms offer a systematic approach to explore mechanisms of complex chemical processes. However, the resulting reaction networks are so vast that an exploration of all potentially accessible intermediates is computationally too demanding. This renders brute-force explorations unfeasible, while explorations with completely pre-defined intermediates or hard-wired chemical constraints, such as element-specific coordination numbers, are not flexible enough for complex chemical systems. Here, we introduce a STEERING WHEEL to guide an otherwise unbiased automated exploration. The STEERING WHEEL algorithm is intuitive, generally applicable, and enables one to focus on specific regions of an emerging network. It also allows for guiding automated data generation in the context of mechanism exploration, catalyst design, and other chemical optimization challenges. The algorithm is demonstrated for reaction mechanism elucidation of transition metal catalysts. We highlight how to explore catalytic cycles in a systematic and reproducible way. The exploration objectives are fully adjustable, allowing one to harness the STEERING WHEEL for both structure-specific (accurate) calculations as well as for broad high-throughput screening of possible reaction intermediates.

Autonomous Reaction Network Exploration in Homogeneous and Heterogeneous Catalysis.

Autonomous computations that rely on automated reaction network elucidation algorithms may pave the way to make computational catalysis on a par with experimental research in the field. Several advantages of this approach are key to catalysis: (i) automation allows one to consider orders of magnitude more structures in a systematic and open-ended fashion than what would be accessible by manual inspection. Eventually, full resolution in terms of structural varieties and conformations as well as with respect to the type and number of potentially important elementary reaction steps (including decomposition reactions that determine turnover numbers) may be achieved. (ii) Fast electronic structure methods with uncertainty quantification warrant high efficiency and reliability in order to not only deliver results quickly, but also to allow for predictive work. (iii) A high degree of autonomy reduces the amount of manual human work, processing errors, and human bias. Although being inherently unbiased, it is still steerable with respect to specific regions of an emerging network and with respect to the addition of new reactant species. This allows for a high fidelity of the formalization of some catalytic process and for surprising in silico discoveries. In this work, we first review the state of the art in computational catalysis to embed autonomous explorations into the general field from which it draws its ingredients. We then elaborate on the specific conceptual issues that arise in the context of autonomous computational procedures, some of which we discuss at an example catalytic system. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11244-021-01543-9.

Expansive Quantum Mechanical Exploration of Chemical Reaction Paths.

Quantum mechanical methods have been well-established for the elucidation of reaction paths of chemical processes and for the explicit dynamics of molecular systems. While they are usually deployed in routine manual calculations on reactions for which some insights are already available (typically from experiment), new algorithms and continuously increasing capabilities of modern computer hardware allow for exploratory open-ended computational campaigns that are unbiased and therefore enable unexpected discoveries. Highly efficient and even automated procedures facilitate systematic approaches toward the exploration of uncharted territory in molecular transformations and dynamics. In this work, we elaborate on such explorative approaches that range from reaction network explorations with (stationary) quantum chemical methods to explorative molecular dynamics and migrant wave packet dynamics. The focus is on recent developments that cover the following strategies. (i) Pruning search options for elementary reaction steps by heuristic rules based on the first-principles of quantum mechanics: Rules are required for reducing the combinatorial explosion of potentially reactive atom pairings, and rooting them in concepts derived from the electronic wave function makes them applicable to any molecular system. (ii) Enforcing reactive events by external biases: Inducing a reaction requires constraints that steer and direct elementary-step searches, which can be formulated in terms of forces, velocities, or supplementary potentials. (iii) Manual steering facilitated by interactive quantum mechanics: As ultrafast quantum chemical methods allow for real-time manual interactions with molecular systems, human-intuition-guided paths can be easily explored with suitable human-machine interfaces. (iv) New approaches for transition-state optimization with continuous curve representations can provide stable schemes to be driven in an automated way by allowing for an efficient tuning of the curve's parameters (instead of a manipulation of a collection of structures along the path), and (v) reactive molecular dynamics and direct wave packet propagation exploit the equations of motion of an underlying mechanical theory (usually, classical Newtonian mechanics or Schrödinger quantum mechanics). Explorative approaches are likely to replace the current state of the art in computational chemistry, because they reduce the human effort to be invested in reaction path elucidations, they are less prone to errors and bias-free, and they cover more extensive regions of the relevant configuration space. As a result, computational investigations that rely on these techniques are more likely to deliver surprising discoveries.

Health Sentinel: A mobile crowdsourcing platform for self-reported surveys provides early detection of COVID-19 clusters in San Luis Potosí, Mexico.

BACKGROUND: The Health Sentinel (Centinela de la Salud, CDS), a mobile crowdsourcing platform that includes the CDS app, was deployed to assess its utility as a tool for COVID-19 surveillance in San Luis Potosí, Mexico. METHODS: The CDS app allowed anonymized individual surveys of demographic features and COVID-19 risk of transmission and exacerbation factors from users of the San Luis Potosí Metropolitan Area (SLPMA). The platform's data processing pipeline computed and geolocalized the risk index of each user and enabled the analysis of the variables and their association. Point process analysis identified geographic clustering patterns of users at risk and these were compared with the patterns of COVID-19 cases confirmed by the State Health Services. RESULTS: A total of 1554 COVID-19 surveys were administered through the CDS app. Among the respondents, 50.4 % were men and 49.6 % women, with an average age of 33.5 years. Overall risk index frequencies were, in descending order: no-risk 77.8 %, low risk 10.6 %, respiratory symptoms 6.7 %, medium risk 1.4 %, high risk 2.0 %, very high risk 1.5 %. Comorbidity was the most frequent vulnerability category (32.4 %), followed by the inability to keep home lockdown (19.2 %). Statistically significant risk clusters identified at a spatial scale between 5 and 730 m coincided with those in neighborhoods containing substantial numbers of confirmed COVID-19 cases. CONCLUSIONS: The CDS platform enables the analysis of the sociodemographic features and spatial distribution of individual risk indexes of COVID-19 transmission and exacerbation. It is a useful epidemiological surveillance and early detection tool because it identifies statistically significant and consistent risk clusters in neighborhoods with a substantial number of confirmed COVID-19 cases.

Quantum Chemical Microsolvation by Automated Water Placement.

We developed a quantitative approach to quantum chemical microsolvation. Key in our methodology is the automatic placement of individual solvent molecules based on the free energy solvation thermodynamics derived from molecular dynamics (MD) simulations and grid inhomogeneous solvation theory (GIST). This protocol enabled us to rigorously define the number, position, and orientation of individual solvent molecules and to determine their interaction with the solute based on physical quantities. The generated solute-solvent clusters served as an input for subsequent quantum chemical investigations. We showcased the applicability, scope, and limitations of this computational approach for a number of small molecules, including urea, 2-aminobenzothiazole, (+)-syn-benzotriborneol, benzoic acid, and helicene. Our results show excellent agreement with the available ab initio molecular dynamics data and experimental results.

Comprehensive Characterization of a Porcine Model of The "Small-for-Flow" Syndrome.

INTRODUCTION: The term "Small-for-Flow" reflects the pathogenetic relevance of hepatic hemodynamics for the "Small-For-Size" syndrome and posthepatectomy liver failure. We aimed to characterize a large-animal model for studying the "Small-for-Flow" syndrome. METHODS: We performed subtotal (90%) hepatectomies in 10 female MiniPigs using a simplified transection technique with a tourniquet. Blood tests, hepatic and systemic hemodynamics, and hepatic function and histology were assessed before (Bas), 15 min (t-15 min) and 24 h (t-24 h) after the operation. Some pigs underwent computed tomography (CT) scans for hepatic volumetry (n = 4) and intracranial pressure (ICP) monitoring (n = 3). Postoperative care was performed in an intensive care unit environment. RESULTS: All hepatectomies were successfully performed, and hepatic volumetry confirmed liver remnant volumes of 9.2% [6.2-11.2]. The hepatectomy resulted in characteristic hepatic hemodynamic alterations, including portal hyperperfusion, relative decrease of hepatic arterial blood flow, and increased portal pressure (PP) and portal-systemic pressure gradient. The model reproduced major diagnostic features including the development of cholestasis, coagulopathy, encephalopathy with increased ICP, ascites, and renal failure, hyperdynamic circulation, and hyperlactatemia. Two animals (20%) died before t-24 h. Histological liver damage was observed at t-15 min and at t-24 h. The degree of histological damage at t-24 h correlated with intraoperative PP (r = 0.689, p = 0.028), hepatic arterial blood flow (r = 0.655, p = 0.040), and hepatic arterial pulsatility index (r = 0.724, p = 0.066). All animals with intraoperative PP > 20 mmHg presented liver damage at t-24 h. CONCLUSION: The present 90% hepatectomy porcine experimental model is a feasible and reproducible model for investigating the "Small-for-Flow" syndrome.

Preconditioning by portal vein embolization modulates hepatic hemodynamics and improves liver function in pigs with extended hepatectomy.

BACKGROUND: Portal vein embolization is performed weeks before extended hepatic resections to increase the future liver remnant and prevent posthepatectomy liver failure. Portal vein embolization performed closer to the operation also could be protective, but worsening of portal hyper-perfusion is a major concern. We determined the hepatic hemodynamic effects of a portal vein embolization performed 24 hours prior to hepatic operation. METHODS: An extended (90%) hepatectomy was performed in swine undergoing (portal vein embolization) or not undergoing (control) a portal vein embolization 24 hours earlier (n = 10/group). Blood tests, hepatic and systemic hemodynamics, hepatic function (plasma disappearance rate of indocyanine green), liver histology, and volumetry (computed tomographic scanning) were assessed before and after the hepatectomy. Hepatocyte proliferating cell nuclear antigen expression and hepatic gene expression also were evaluated. RESULTS: Swine in the control and portal vein embolization groups maintained stable systemic hemodynamics and developed similar increases of portal blood flow (302 ± 72% vs 486 ± 92%, P = .13). Portal pressure drastically increased in Controls (from 9.4 ± 1.3 mm Hg to 20.9 ± 1.4 mm Hg, P < .001), while being markedly attenuated in the portal vein embolization group (from 11.4 ± 1.5 mm Hg to 16.1 ± 1.3 mm Hg, P = .061). The procedure also improved the preservation of the hepatic artery blood flow, liver function, and periportal edema. These effects occurred in the absence of hepatocyte proliferation or hepatic growth and were associated with the induction of the vasoprotective gene Klf2. CONCLUSION: Portal vein embolization preconditioning represents a potential hepato-protective strategy for extended hepatic resections. Further preclinical studies should assess its medium-term effects, including survival. Our study also supports the relevance of hepatic hemodynamics as the main pathogenetic factor of post-hepatectomy liver failure.

Rapid suppression of Onchocerca volvulus transmission in two communities of the Southern Chiapas focus, Mexico, achieved by quarterly treatments with Mectizan.

The impact of quarterly Mectizan (ivermectin) treatments on transmission, microfiladermia, and ocular lesions was evaluated in two formerly hyperendemic communities (Las Golondrinas and Las Nubes II) located in the main endemic focus for onchocerciasis in Southern Chiapas, Mexico. The data suggest that Onchocerca volvulus transmission has been suppressed after elimination of microfiladermia in these two communities. Increasing the frequency of Mectizan treatment to four times per year appears to have resulted in the rapid suppression of transmission in communities with residual transmission.

Determinacion de ruidos permisibles en la operacion de aeronaves en torno a aeropuertos

El presente trabajo, en su primera parte y con el fin de abordar de manera eficaz el problema del ruido aeronautico, repasara los conceptos generales del ruido, su propagacion y la molestia que ocasiona, las unidades de medicion y fuentes del mismo. Posteriormente se presentaran diferentes soluciones en cuanto a medidas de mitigacion , vigilancia y sistemas de control utilizados de manera mas o menos general en los diferentes paises; luego se analizaran las diversas formas de utilizacion de los terrenos circundante a un aeropuerto y el grado de compatibilidad de cada uno de los usos con el ruido de la operacion cercana de aeronaves. De manera conducente, se analizara la planificacion de utilizacion de los terrenos y la zonificacion de los mismos, como medidas fundamentales para la prevencion y lucha contra el problema del ruido aeronautico. En una segunda parte, el trabajo planteara, a manera de un estudio de aplicacion, la situacion del ruido aeronautico en torno al aeropuerto de El Alto-La Paz que incluye, un diagnostico del transporte aereo, las condiciones del mismo, en particular el movimiento de aeronaves y su proyeccion, las caracteristicas operacionales en cuanto al uso de pistas, regimen de vientos, condiciones naturales y sociales circundantes, el uso actual de los terrenos y la influencia del ruido de aeronaves en las zonas urbanas cercanas.