Study of chemical modifications in acidified ignitable liquids analysed by GC-MS

In this work, mixtures of gasoline with sulphuric acid and diesel fuel with sulphuric acid were analysed by gas chromatography&-mass spectrometry (GC&-MS). The results showed considerable qualitative and semi-quantitative modifications in the chromatographic profiles of the ignitable liquids (ILs). In the case of acidified gasoline, the alteration of the abundances of aromatic compounds and the hydrolysis of an oxygenated compound such as methyl tert-butyl ether (MTBE), in addition to the immediate and unexpected appearance of tert-butylated compounds were observed. In the case of acidified diesel fuel, the alteration of aromatic compounds occurred. These sequential changes were then studied in detail in order to explain the chemical modifications taking place. These extensive chemical modifications may be considered as a new chromatographic profile distortion effect, the acidification of ILs. As such modifications are not generally taken into account in the criteria followed to assess the classification of an IL, we propose some recommendations helping to the identification of acidified ILs. This information can be especially useful to detect and identify non-burned ILs from seized or failed improvised incendiary devices made with mixtures of sulphuric acid&-IL, or ILs altered intentionally with the aim to modify their composition

Analysis of pre-ignited Improvised Incendiary Devices using portable Raman

In this work, the use of a portable Raman spectrometer is evaluated for the non-invasive analysis of two types of pre-ignited improvised incendiary devices (IIDs), the classic Molotov cocktails and the chemical ignition Molotov cocktails (CIMCs). The most common ignitable liquids (ILs) used to make classic Molotov cocktails (gasoline, diesel fuel, kerosene and ethanol) were measured in seven different clear and colored glass bottles to evaluate if the container features could hamper the Raman measurements. The results showed that the portable Raman spectrometer can be employed to detect ILs in glass bottles without disturbances. Chemical changes on the ILs are produced when they are mixed with acid; therefore, to evaluate the use of the portable Raman spectrometer for the analysis of CIMCs required an investigation of how time and movement influence the measurements. Thus, two different IL&-sulfuric acid mixtures commonly used to make CIMCs (gasoline&-sulfuric acid and diesel fuel&-sulfuric acid) were measured over time under static and motion conditions. In spite of the intense fluorescence encountered in both CIMCs, it was possible to identify the acid and the gasoline for the first hours of the reaction both in the static and motion experiments. Concerning the diesel fuel present in the CIMC, it underwent instantaneous chemical changes under both measurement conditions, showing high fluorescence that impeded its identification. In view of the results achieved, the portable Raman spectrometer can be a useful instrument for the rapid, non-invasive and safe analysis of pre-ignited IIDs

Study of Spectral Modifications in Acidified Ignitable Liquids by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy

In this work, the spectral characteristics of two types of acidified gasoline and acidified diesel fuel are discussed. Neat and acidified ignitable liquids (ILs) infrared absorption spectra obtained by attenuated total reflection Fourier transform infrared spectroscopy were compared in order to identify the modifications produced by the reaction of the ILs with sulfuric acid. Several bands crucial for gasoline identification were modified, and new bands appeared over the reaction time. In the case of acidified diesel fuel, no significant modifications were observed. Additionally, the neat and acidified ILs spectra were used to perform a principal components analysis in order to confirm objectively the results. The complete discrimination among samples was successfully achieved, including the complete differentiation among gasoline types. Taking into account the results obtained in this work, it is possible to propose spectral fingerprints for the identification of non-burned acidified ILs in forensic investigations related with arson or the use of improvised incendiary devices (IIDs)

Analytical tools for the analysis of fire debris. A review: 2008-2015

The analysis of fire debris evidence might offer crucial information to a forensic investigation, when for instance, there is suspicion of the intentional use of ignitable liquids to initiate a fire. Although the evidence analysis in the laboratory is mainly conducted by a handful of well-established methodologies, during the last eight years several authors proposed noteworthy improvements on these methodologies, suggesting new interesting approaches. This review critically outlines the most up-to-date and suitable tools for the analysis and interpretation of fire debris evidence. The survey about analytical tools covers works published in the 2008&-2015 period. It includes sources of consensus-classified reference samples, current standard procedures, new proposals for sample extraction and analysis, and the most novel statistical tools. In addition, this review provides relevant knowledge on the distortion effects of the ignitable liquid chemical fingerprints, which have to be considered during interpretation of results

Acid alteration of several ignitable liquids of potential use in arsons

Ignitable liquids such as fuels, alcohols and thinners can be used in criminal activities, for instance arsons. Forensic experts require to know their chemical compositions, as well as to understand how different modification effects could impact them, in order to detect, classify and identify them properly in fire debris. The acid alteration/acidification of ignitable liquids is a modification effect that sharply alters the chemical composition, for example, of gasoline and diesel fuel, interfering in the forensic analysis and result interpretation. However, to date there is little information about the consequences of this effect over other accelerants of interests. In this research paper, the alteration by sulfuric acid of several commercial thinners and other accelerants of potential use in arsons is studied in-depth. For that purpose, spectral (by ATR-FTIR) and chromatographic (by GC&-MS) data were obtained from neat and acidified samples. Then, the spectral and chromatographic modifications of each studied ignitable liquid were discussed, proposing several chemical mechanisms that explain the new by-products produced and the gradual disappearance of the initial compounds. Hydrolysis, Fischer esterification and alkylation reactions are involved in the modification of esters, alcohols, ketones and aromatic compounds of the studied ignitable liquids. This information could be crucial for correctly identifying these accelerants. Additionally, an exploratory analysis revealed that some of the most altered ignitable liquid samples might be very similar with each other, which could have impact on casework

Carbon nanotube-Cu hybrids enhanced catalytic activity in aqueous media

V. González, O. Martín and J. Baselga wish to thank Ministerio de Economía y Competitividad for funding through Grant MAT2010-17091. Authors also wish to thank to Sofía M. Vega for XPS measurements, Juan P. Fernández for TGA measurements and Lakshmy Pulickal Rajukumar for EDX measurements. C. Martín-Alberca thanks the University of Alcalá for his pre-doctoral Grant

Long runs of homozygosity are associated with Alzheimer's disease

Altres ajuts: The Genome Research at Fundació ACE project (GR@ACE) is supported by Fundación bancaria "La Caixa," Grifols SA and Fundació ACE. L.M.R. is supported by Consejería de Salud de la Junta de Andalucía (Grant PI-0001/2017).Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer's disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a fine-scale ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.) We detected an increase of homozygosity in AD cases compared to controls [ β (CI 95%) = 0.070 (0.037-0.104); P = 3.91 × 10 −5 ; β (CI95%) = 0.043 (0.009-0.076); P = 0.013]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 × 10 −16). A significant ROH association with AD risk was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), (β (CI 95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 × 10 −4), previously related to AD. Next, to search for recessive candidate variants in ROHs, we constructed a homozygosity map of inbred AD cases extracted from an outbred population and explored ROH regions in whole-exome sequencing data (N = 1449). We detected a candidate marker, rs117458494, mapped in the SPON1 locus, which has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting that recessive effects may explain a proportion of AD heritability

Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro

Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence.Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy –performed in a large and diverse chemolibrary– complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening.Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 μM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12–20 μM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7–45 μM).Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known “garbage in, garbage out” machine learning principle

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Analytical solutions for the forensic analysis of improvised incendiary devices and consumer fireworks

Premio Extraordinario de Doctorado de la UAH en el año académico 2015-2016En esta Tesis Doctoral se buscan soluciones analíticas para el estudio exitoso, desde el punto de vista forense, de dos grupos de dispositivos: artefactos incendiarios improvisados (IIDs) y artículos pirotécnicos. Este objetivo general se ha abordado porque peritos forenses oficiales nos solicitaron más información sobre configuraciones y composiciones químicas de ambos tipos de artefactos, y el desarrollo de procedimientos de análisis adecuados para su estudio. En concreto, pidieron soluciones analíticas para el estudio del cóctel Molotov de iniciación química (CIMC) y los llamados artificios pirotécnicos. Con el fin de afrontar el objetivo general de la Tesis, se consideraron los siguientes objetivos específicos: Por un lado, investigar la diversidad real de configuraciones y composiciones de ambos grupos de artefactos para así ofrecer información fidedigna de interés forense. Por otra parte, desarrollar nuevas metodologías específicas mediante técnicas separativas y espectroscópicas para el análisis de muestras relacionadas con ambos grupos de artefactos. Además, y como consecuencia de estos dos primeros objetivos específicos, proporcionar soluciones y recomendaciones para la interpretación objetiva y fiable de los resultados analíticos obtenidos de ambos grupos de artefactos. Por consiguiente, en la primera parte de la tesis, el Capítulo 1 proporciona información fidedigna sobre composiciones y configuraciones de IIDs, además de información acerca del análisis de muestras relacionadas con estos artefactos. A continuación, el Capítulo 2 muestra el estudio de la composición aniónica de restos de incendio de CIMCs. Se proporciona un método analítico para el tratamiento de muestras y análisis cualitativo de restos de CIMC mediante electroforesis capilar (CE). Además, se proporcionan marcadores anionicos que aportan información relevante para ayudar en la interpretación de los resultados y en la elaboración de informes periciales. El Capítulo 3 trata del estudio de líquidos inflamables (ILs) acidificados y de residuos de líquidos inflamables (ILRs) acidificados. Se analizan mezclas de gasolina o diésel con ácido sulfúrico mediante una metodología optimizada basada en cromatografía de gases-espectrometría de masas (GC-MS). Los resultados mostraron modificaciones considerables en los perfiles cromatográficos de los ILs, tanto diferencias cualitativas como semi-cuantitativas. Además, se propone una metodología para el estudio de ILRs acidificados procedentes de restos de incendio mediante micro-extracción en fase sólida seguida de análisis por GC-MS (SPME-GC-MS). En el Capítulo 4 se estudian CIMCs y cócteles Molotov clásicos pre-iniciados por espectroscopia Raman y FTIR con reflexión total atenuada (ATR). Se utilizó con éxito un espectrómetro Raman portátil para el análisis no invasivo ILs comunes en la preparación de cócteles Molotov clásicos (gasolina, diésel, queroseno y etanol) dentro de siete botellas de cristal. Además, se evaluó el uso de este instrumento para el análisis de CIMCs. Por otro lado, se discuten las características espectrales infrarrojas obtenidas mediante un aparato ATR-FTIR de dos tipos de gasolinas acidificadas y un tipo de diésel acidificado. Adicionalmente, se estudiaron los espectros de ILs frescos y acidificados mediante el uso de herramientas quimiométricas, en concreto se realizó un Análisis de Componentes Principales (PCA). La segunda parte de esta tesis doctoral comienza con el Capítulo 5, donde se ofrece una revisión de las composiciones habituales de artificios pirotécnicos y de todas las metodologías publicadas hasta la fecha para la determinación de la composición química a partir de artificios pirotécnicos intactos o sus residuos. El Capítulo 6 investiga la variabilidad real de configuraciones y composiciones químicas de artificios pirotécnicos. Se analizaron muestras pre-explosión (mechas y cargas) y muestras de residuos post-explosión mediante una metodología optimizada para la preparación de muestras y análisis por CE con el objetivo de determinar sus composiciones aniónicas. Además, se desarrolló una metodología con un sistema de CE portátil que utiliza dos capilares con dos detectores de conductividad y una única disolución tampón, para la identificación simultánea de aniones y cationes de muestras de artificios pirotécnicos. En el Capítulo 7, se evaluó un procedimiento rápido y simple para el muestreo y análisis de residuos post-explosión de artificios pirotécnicos usando un instrumento ATR-FTIR portátil, y se estudiaron los espectros de restos post-explosión de 5 artificios pirotécnicos diferentes con el objetivo de identificar sus composiciones químicas originales. Se observaron varias bandas de absorción IR relacionadas con los productos de combustión y los compuestos originales. Un estudio adicional usando herramientas quimiométricas encontró varias variables que podrían influir en los resultados durante el proceso de muestreo. Como conclusión, esta Tesis Doctoral presenta soluciones analíticas para el estudio forense de vestigios de IIDs y artificios pirotécnicos que pueden ayudar a resolver casos forenses relacionados con estos artefactos