Design and Synthesis of N-Doped Carbons as Efficient Metal-Free Catalysts in the Hydrogenation of 1-Chloro-4-Nitrobenzene

Metal-free catalysts based on nitrogen-doped porous carbons were designed and synthesized from mixtures of melamine as nitrogen and carbon sources and calcium citrate as carbon source and porogen system. Considering the physicochemical and textural properties of the prepared carbons, a melamine/citrate ratio of 2:1 was selected to study the effect of the pyrolysis temperature. It was observed that a minimum pyrolysis temperature of 750 ◦C is required to obtain a carbonaceous structure. However, although there is a decrease in the nitrogen amount at higher pyrolysis temperatures, a gradual development of the porosity is produced from 750 ◦C to 850 ◦C. Above that temperature, a deterioration of the carbon porous structure is produced. All the prepared carbon materials, with no need for a further activation treatment, were active in the hydrogenation reaction of 1-chloro-4-nitrobenzene. A full degree of conversion was reached with the most active catalysts obtained from 2:1 melamine/citrate mixtures pyrolyzed at 850 ◦C and 900 ◦C, which exhibited a suitable compromise between the N-doping level and developed mesoporosity that facilitates the access of the reactants to the catalytic sites. What is more, all the materials showed 100% selectivity for the hydrogenation of the nitro group to form the corresponding chloro-aniline.Financial support from the Ministry of Science and Innovation (Spain, PID2019-108453GB-C21) and Generalitat Valenciana (Spain, CIPROM/2021/022) is gratefully acknowledged

N-Doped Activated Carbons from Polypyrrole – Effect of Steam Activation Conditions

Polypyrrole (PPy) has been prepared by oxidative polymerization of pyrrole and used as a raw material for the preparation of N-doped activated carbons. Thus, PPy has been pyrolyzed at 900 °C and then activated with steam under different activation conditions (time and temperature). This has allowed for the preparation of activated carbons with different porosity development and nitrogen content, as well as distinctive distribution of nitrogen species. It has been observed that the presence of nitrogen functionalities favors water adsorption at low relative pressures but, at relative pressures higher than 0.5 it is determined by the porosity development.Financial support from Ministerio de Ciencia e Innovación (Spain, Project PID2019-108453GB-C21) is gratefully acknowledged. Open access funding enabled and organized by Projekt DEAL

Accelerating the B&B algorithm for integer programming based on flatness information: an approach applied to the multidimensional knapsack problem

This paper presents a new branching rule based on the flatness of a polyhedron associated to the set of constraints in an integer linear programming problem. The rule called Flatness II is a heuristic technique used with the branch-and-bound method. The rule is concerned with the minimum integer width vector. Empirical evidence supports the conjecture that the direction with the highest value of the vector’s components indicates a suitable branching direction. The paper provides theoretical results demonstrating that the columns of the matrix A corresponding to a set of constraints Ax≤b may be used to estimate the minimum integer width vector; this fact is used for constructing a new version of the branching rule as was reported in a previous paper by the authors. In addition, the new rule uses a branching direction that chooses the child node closest to the integer value (either up or down). Thus, it uses a variable rule for descending the tree. Every time a new sub-problem is solved, the list of remaining unsolved sub-problems is analyzed, with priority given to those problems with a minimum objective function value estimate. The conclusions of the work are based on knapsack problems from the knapsack OR-Library. From the results, it is concluded that the new rule Flatness II presents low execution times and minimal number of nodes generated

Long-term survival in a patient with progressive multifocal leukoencephalopathy after therapy with rituximab, fludarabine and cyclophosphamide for chronic lymphocytic leukemia

A 50-year-old male with chronic lymphocytic leukemia (CLL) was treated with fludarabine, cyclophosphamide and rituximab, which produced a complete remission. Eight months after the last dose of rituximab he had visual disturbance, diminished muscular strength in the right arm and vesicular-papular lesions in the left ophthalmic branch region of the V cranial nerve. These were initially interpreted as herpes virus encephalopathy (HVE), but brain magnetic resonance imaging (MRI) showed evidence of demyelination consistent with progressive multifocal leukoencephalopathy (PML). Cerebrospinal fluid (CSF) analysis was negative for varicella zoster virus (VZV) and John Cunningham virus (JCV) DNA. The clinical suggestion of PML prompted us to perform a brain biopsy and to start treatment with mefloquine. In the brain biopsy, histopathological features of demyelination were described and the polymerase chain reaction (PCR) identified JCV, confirming the diagnosis of PML. Treatment with mefloquine (250 mg/week) and dexamethasone (4 mg/day) was started and maintained for 6 months. A year later there was an almost complete resolution of the MRI lesions and the patient achieved a stable clinical state with persisting motor impairment and severe epilepsy. The patient is alive 38 months after diagnosis of PML, which is the longest known survival to date.Supported by grants from the Fondo de Investigaciones Sanitarias - Ministerio de Ciencia e Innovación (PI12/1832), Plan Nacional of I + D + I co-financed by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER). HG has a grant from Fundación BBVA - Fundación Carolina.S

Doped activated carbons obtained from nitrogen and sulfur-containing polymers as metal-free catalysts for application in nitroarenes hydrogenation

Activated carbons doped with nitrogen and/or sulfur have been obtained by pyrolysis followed of steam activation of a sulfur containing polymer (polythiophene) and two nitrogen-containing polymers (polyaniline and polypyrrole). These polymers were synthesized by oxidative chemical polymerization in aqueous media of their corresponding monomers. The influence of the steam activation on the textural properties and surface chemistry of the carbons has been evaluated and their catalytic activity has been determined in the hydrogenation reaction of 1-chloro-4-nitrobenzene. The degree of conversion in the reaction depends on the development of adequate porosity in the activated carbon (which is determined by the activation conditions) together with the presence of heteroatoms that act as active catalytic sites, with S showing considerably greater effectiveness than N. A compromise between an acceptable level of doping with sulfur and an adequate porosity is necessary, which has been achieved in a carbon obtained from polythiophene pyrolyzed at 900 °C and steam activated at 800 °C for 4 h, with a specific surface area of 742 m2/g and S content of 1.71 at%.Financial support from Spain Ministry of Science and Innovation (PID2019-108453GB-C21) is gratefully acknowledged

On Improvement of Detection of Obstructive Sleep Apnea by Partial Least Square-based Extraction of Dynamic Features

This paper presents a methodology for Obstructive Sleep Apnea (OSA) detection based on the HRV analysis, where as a measure of relevance PLS is used. Besides, two different combining approaches for the selection of the best set of contours are studied. Attained results can be oriented in research focused on finding alternative methods minimizing the HRV-derived parameters used for OSA diagnosing, with a diagnostic accuracy comparable to a polysomnogram. For two classes (normal, apnea) the results for PLS are: specificity 90%, sensibility 91% and accuracy 93.56%

Hydrogenation of 4-nitrochlorobenzene catalysed by cobalt nanoparticles supported on nitrogen-doped activated carbon

The hydrogenation of nitroarenes to produce the corresponding amines using dihydrogen as reducing agent has an important industrial role, since it allows to obtain important added-value products. This reaction needs the help of a catalyst to proceed. Many catalysts have been already tested and studied. Most of them are based on noble metals supported on metal oxides. These catalysts perform well, but they are expensive and thus, alternative systems are needed. In this context, cobalt-based catalysts have emerged as adequate alternatives, despite cobalt nanoparticles per se are not very active for this reaction. A way to improve the catalytic activity of cobalt nanoparticles is by supporting them on a support with functional groups that are able to change their intrinsic properties and to enhance their catalytic properties. In this sense, N-containing carbons are promising candidates to be used as support, since nitrogen functionalities may modify the catalytic properties of cobalt. In this work, cobalt nanoparticles supported on N-doped activated carbons have been prepared and studied as catalysts for the hydrogenation of 1-chloro-4-nitrobencene to the corresponding chloro-aniline. It is demonstrated that the catalytic activity is enhanced by the presence of nitrogen species in the support. When the temperature of the catalyst activation treatment (reduction under flowing hydrogen) is increased, the catalytic activity increases drastically in the presence of nitrogen functionalities on the support. The catalysts have been characterised by transmission electron microscopy (TEM), temperature-programmed reduction (TPR), X-ray diffraction, X-ray photoelectron spectroscopi (XPS) and N2 adsorption at 77 K. It has been found that the enhanced catalytic activity was due to two different factors, namely the interaction of the cobalt particles with the nitrogen functional groups (forming Co4N), and the development of mesopores in the support during the activation process that increases the accessibility of reactants to the active sites.Authors acknowledge financial support by MINECO (Spain) through the projects MAT2017-86992-R and MAT2016-80285-P and the European Union for the project “eForFuel”, grant agreement 763911. J. C. S. R. would like to thank the Spanish Ministry of Science and Innovation for financial support through the Ramón y Cajal Program, Grant: RYC-2015-19230 J. C. S. R. would also like to thank Junta de Andalucía for financial support through the projects PY18-RE-0012 and IE18_0047_FUNDACIÓN LOYOLA

Forecasting Chaotic Series in Manufacturing Systems by Vector Support Machine Regression and Neural Networks

Currently, it is recognized that manufacturing systems are complex in their structure and dynamics. Management, control and forecasting of such systems are very difficult tasks due to complexity. Numerous variables and signals vary in time with different patterns so that decision makers must be able to predict the behavior of the system.This is a necessary capability in order to keep the system under a safe operation. This also helps to prevent  emergencies and the occurrence of critical events that may put in danger human beings and capital resources, such as expensive equipment and valuable production. When dealing with chaotic systems, the management, control, and forecasting are very difficult tasks. In this article an application of neural networks and vector support machines for the forecasting of the time varying average number of parts in a waiting line of a manufacturing system having a chaotic behavior, is presented. The best results were obtained with least square support vector machines and for the neural networks case, the best forecasts, are those with models employing the invariants characterizing the system’s dynamics

Conducting Polymer–TiO2 Hybrid Materials: Application in the Removal of Nitrates from Water

Materials able to produce the reduction of nitrate from water without the need of a metal catalyst and with avoiding the use of gaseous hydrogen have been developed by combining the synergistic properties of titania and two conducting polymers. Polymerization of aniline and pyrrol on titanium dioxide in the presence of two different oxidants/dopants (iron trichloride or potassium persulfate) has been evaluated. The resulting hybrid materials have good thermal stability imparted by the titania counterpart, and a considerable conductivity provided by the conducting polymers. The capability of the hybrid materials of reducing aqueous nitrate has been assessed and compared to the catalytic hydrogenation of nitrate using a platinum catalyst supported on these hybrid synthesized materials. The mechanism of nitrate abatement implies adsorption of nitrate on the polymer by ion exchange with the dopant anion, followed by the reduction of nitrate. The electron transfer from titania to the conducting polymer in the hybrid material favors the reductive ability of the polymer, in such a way that nitrate is selectively reduced with a very low production of undesirable side products. The obtained results show that the activity and selectivity of the catalytic reduction of nitrate with dihydrogen in the presence of a platinum catalyst supported on the hybrid materials are considerably lower than those of the metal-free nanocomposites.Financial support from Generalitat Valenciana, Spain (PROMETEOII/2014/004) and Ministry of Economy and Competitivity (MAT2016-80285-P) is gratefully acknowledged. E.S. acknowledges the Spanish MINECO and AEI/FEDER (ref CTQ2015-74494-JIN) and the University of Alicante (ref UATALENTO16-03)

On optimal temozolomide scheduling for slowly growing glioblastomas

Background: Temozolomide (TMZ) is an oral alkylating agent active against gliomas with a favorable toxicity profile. It is part of the standard of care in the management of glioblastoma (GBM), and is commonly used in low-grade gliomas (LGG). In-silico mathematical models can potentially be used to personalize treatments and to accelerate the discovery of optimal drug delivery schemes. Methods: Agent-based mathematical models fed with either mouse or patient data were developed for the in-silico studies. The experimental test beds used to confirm the results were: mouse glioma models obtained by retroviral expression of EGFR-wt/EGFR-vIII in primary progenitors from p16/p19 ko mice and grown in-vitro and in-vivo in orthotopic allografts, and human GBM U251 cells immobilized in alginate microfibers. The patient data used to parametrize the model were obtained from the TCGA/TCIA databases and the TOG clinical study. Results: Slow-growth "virtual" murine GBMs benefited from increasing TMZ dose separation in-silico. In line with the simulation results, improved survival, reduced toxicity, lower expression of resistance factors, and reduction of the tumor mesenchymal component were observed in experimental models subject to long-cycle treatment, particularly in slowly growing tumors. Tissue analysis after long-cycle TMZ treatments revealed epigenetically driven changes in tumor phenotype, which could explain the reduction in GBM growth speed. In-silico trials provided support for implementation methods in human patients. Conclusions: In-silico simulations, in-vitro and in-vivo studies show that TMZ administration schedules with increased time between doses may reduce toxicity, delay the appearance of resistances and lead to survival benefits mediated by changes in the tumor phenotype in slowly-growing GBMs.This research was funded by the James S. Mc. Donnell Foundation (USA) 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer (Collaborative award 220020560, doi:10.37717/220020560); Ministry of Education, Science and Technological Development, Republic of Serbia (ref. number 451-03-9/2021-14/200007); Ministerio de Ciencia e Innovación and FEDER funds, Spain (grant number PID2019-110895RB-I00, doi: 10.13039/501100011033 to VMP-G, and RTI2018-093596 and PI21CIII/00002 to PS-G); and Universidad de Castilla-La Mancha (grant number 2020-PREDUCLM-15634 to JJ-S).S