LC-MS/MS analysis of 2-aminothiazoline-4-carboxylic acid as a forensic biomarker for cyanide poisoning

AIM: To demonstrate the potential of using 2-aminothiazoline-4-carboxylic acid(ATCA) as a novel biomarker/forensic biomarker for cyanide poisoning. METHODS: A sensitive method was developed and employed for the identification and quantification of ATCA in biological samples, where the sample extraction and clean up were achieved by solid phase extraction(SPE). After optimization of SPE procedures, ATCA was analyzed by high performance liquid chromatographytandem mass spectrometry. ATCA levels following the administration of different doses of potassium cyanide(KCN) to mice were measured and compared to endogenous ATCA levels in order to study the significance of using ATCA as a biomarker for cyanide poisoning.RESULTS: A custom made analytical method was established for a new(mice) model when animals were exposed to increasing KCN doses. The application of this method provided important new information on ATCA as a potential cyanide biomarker. ATCA concentration in mice plasma samples were increased from 189 ± 28 ng/mL(n = 3) to 413 ± 66 ng/mL(n = 3) following a 10 mg/kg body weight dose of KCN introduced subcutaneously. The sensitivity of this analytical method proved to be a tool for measuring endogenous level of ATCA in mice organs as follows: 1.2 ± 0.1 μg/g for kidney samples, 1.6 ± 0.1 μg/g for brain samples, 1.8 ± 0.2 μg/g for lung samples, 2.9 ± 0.1 μg/g for heart samples, and 3.6 ± 0.9 μg/g for liver samples. CONCLUSION: This finding suggests that ATCA has the potential to serve as a plasma biomarker / forensic biomarker for cyanide poisoning.

以任何方法剪接:Mdm2位于肿瘤监视的十字路口

鼠双微基因2(Mdm2)是p53最重要的调节基因,同时也是对各种类型细胞应激(包DNA损害和致癌损伤)的主要应答者。尽管已有文章描述了Mdm2基因的替代产物的异常拼接产物,但是关于该变异体的起源、功能和影响,现在尚不清楚。最近发现了一种新的mdm2基因的剪接形式。在该剪接体中,108bp的基因内序列合并到成熟的Mdm2 mRNA中。编码框内终止密码子的额外序列可使Mdm2蛋白明显缩短。最有趣的现象是,阿霉素和放线菌素D能诱导产生一种交替剪接形式,即成熟的Mdm2+108,而其他的DNA损伤剂没有这种诱导作用。Mdm2+108基因可诱导p53的大量快速聚集,证明该交替剪接事件的作用是形成p53的肿瘤监视途径,同时抑制细胞的增殖(该细胞为被有效的遗传毒性化合物所破坏的细胞)。

An Open Source Toolkit for Identifying Comparative Space-time Research Questions

Comparative space-time thinking lies at the heart of spatiotemporally integrated social sciences. The multiple dimensions and scales of socioeconomic dynamics pose numerous challenges for the application and evaluation of public policies in the comparative context. At the same time, social scientists have been slow to adopt and implement new spatiotemporally explicit methods of data analysis due to the lack of extensible software packages, which becomes a major impediment to the promotion of spatiotemporal thinking. The proposed framework will address this need by developing a set of research questions based on space-time-distributional features of socioeconomic datasets. The authors aim to develop, evaluate, and implement this framework in an open source toolkit to comprehensively quantify the changes and level of hidden variation of space-time datasets across scales and dimensions. Free access to the source code allows a broader community to incorporate additional advances in perspectives and methods, thus facilitating interdisciplinary collaboration. Being written in Python, it is entirely cross-platform, lowering transmission costs in research and education.

Cyber Variants of Traditional Crimes and Criminal Law Responses

传统犯罪网络变异的原因是多方面的，直接诱因是网络空间的技术性代际差异；传统犯罪的网络变异表现为犯罪构成要件要素的变异、社会危害性的变异和犯罪形态的变异三个方面。扩张化的司法解释是解决这一问题的首要选择，但其局限性也是明显的；面对网络空间中传统犯罪的变异态势，将部分预备行为提升、独立化为实行行为，将部分共犯行为加以正犯化，将会是未来刑事立法无法回避的两个选择。

Dynamic Hand Gesture Recognition Using 3D-CNN and LSTM Networks

Recognition of dynamic hand gestures in real-time is a difficult task because the system can never know when or from where the gesture starts and ends in a video stream.Many researchers have been working on visionbased gesture recognition due to its various applications.This paper proposes a deep learning architecture based on the combination of a 3D Convolutional Neural Network(3D-CNN)and a Long Short-Term Memory(LSTM)network.The proposed architecture extracts spatial-temporal information from video sequences input while avoiding extensive computation.The 3D-CNN is used for the extraction of spectral and spatial features which are then given to the LSTM network through which classification is carried out.The proposed model is a light-weight architecture with only 3.7 million training parameters.The model has been evaluated on 15 classes from the 20BN-jester dataset available publicly.The model was trained on 2000 video-clips per class which were separated into 80%training and 20%validation sets.An accuracy of 99%and 97%was achieved on training and testing data,respectively.We further show that the combination of 3D-CNN with LSTM gives superior results as compared to MobileNetv2+LSTM.

Quantitative analysis of opioids and cannabinoids in wastewater samples

Wastewater-based epidemiology is an innovative approach that uses the analysis of human excretion products in wastewater to obtain information about exposure to drugs in defined population groups.We developed and validated an analytical method for the simultaneous determination of opioids(morphine,oxycodone,hydrocodone,oxymorphone and hydromorphone),and cannabinoids(△9-tetrahydrocannabinol,11-nor-9-carboxy-tetrahydrocannabinol(THCCOOH)and THCCOOH-glucuronide)in raw-influent wastewater samples by ultra-high performance liquid chromatography-tandem mass spectrometry.Method validation included linearity(5-1000 ng/L for opioids,10-1000 ng/L for cannabinoids),imprecision(<21.2%),accuracy(83%-131%),matrix effect(from-35.1%to-14.7%)and extraction efficiency(25%-84%),limit of detection(1-5 ng/L)and quantification(5-10 ng/L)and auto-sampler stability(no loss detected).River and wastewater samples were collected in triplicate from different locations in New York City and stored at-20℃until analysis.Water from sewage overflow location tested positive for morphine(10.7 ng/L),oxycodone(4.2-23.5 ng/L),oxymorphone(4.8 ng/L)and hydromorphone(4.2 ng/L).Raw influent wastewater samples tested positive for morphine(133.0-258.3 ng/L),oxycodone(31.1-63.6 ng/L),oxymorphone(16.0-56.8 ng/L),hydromorphone(6.8-18.0 ng/L),hydrocodone(4.0-12.8 ng/L)and THCCOOH(168.2-772.0 ng/L).This method is sensitive and specific for opioids and marijuana determination in wastewater samples.

Wastewater analysis for nicotine,cocaine,amphetamines,opioids and cannabis in New York City

According to current surveys and overdoses data,there is a drug crisis in the USA.Wastewater-based epidemiology(WBE)is an evolving discipline that analyses wastewater samples to detect drugs and metabolites to estimate drug consumption in a certain community.This study demonstrates how drug relative presence could be tracked by testing wastewater,providing real-time results,in different boroughs in New York City throughout 1 year.We developed and fully validated two analytical methods,one for 21 drugs and metabolites,including nicotine,cocaine,amphetamines,opioids and cannabis markers;and another for the normalization factor creatinine.Both methods were performed by liquid chromatography tandem mass spectrometry(LC-MS/MS)using positive electrospray ionization,achieving a limit of quantification of 5–10 ng/L for drugs and metabolites,and 0.01 mg/L for creatinine.These methods were applied to 48 one-time grab wastewater samples collected from six wastewater treatment plants in New York City(Manhattan,The Bronx,Queens and Brooklyn),eight different times throughout 2016,before and after major holidays,including Memorial Day,4th of July,Labour Day and New Year’s.In this study,the drug group normalized concentrations present in the wastewater samples,in decreasing order,were cocaine,nicotine,opioids,cannabis and amphetamines.When looking at individual compounds,the one with the highest normalized concentration was benzoylecgonine(BE),followed by cotinine,morphine and 11-nor-9-carboxy-tetrahydrocannabinol(THCCOOH).To estimate community use,these concentrations were multiplied by the corresponding correction factor,and the most present were THCCOOH,followed by BE,cotinine and morphine.When comparing the treatment plants by drug group(nicotine,cocaine,amphetamines,opioids and cannabis),samples collected from The Bronx had the highest normalized concentrations for nicotine,cocaine and opioids;The Bronx and Manhattan for cannabis;and Manhattan and Queens for amphetamines.In most of the cases,no effect due to holiday was observed.This study provides the first snapshot of drug use in New York City and how that changes between key calendar dates employing wastewater analysis.

‘New’unintentionally produced PCBs in the Arctic

Contamination of the Arctic by legacy polychlorinated biphenyls(PCB)is well documented,but the more recent discovery of unintentionally produced(UP)PCBs in the Arctic is a cause for concern.Legacy PCBs are covered by existing international conventions and regular monitoring,and the UP congeners are covered by the Stockholm Convention and the U.S.Toxic Substances Control Act,but systematic monitoring and regulatory enforcement of UP-PCBs are lacking.Sources of UP-PCB are by-products of manufacturing(e.g.pigments)and from thermal sources(e.g.incinerators).Estimates of PCB emissions in China now show UP-PCB eclipsing emissions of legacy PCB.Here we discuss the 209 PCB-congener results from surface snow samples from Lomonosovfonna in 2010 and 2014,a glacial site on Svalbard which,in 2014,shows presence of PCB5,PCB11,and an unusually high amount of PCB52.While PCB5 and PCB11 may not be found in legacy PCB mixtures,PCB52 is in many PCB mixtures,yet dominates none of them as in the 2014 snow sample.Is it possible that these congeners are from UP-PCB processes?A search of the literature shows that PCB5,PCB11 and PCB52 are co-synthesis products of pigment production and that PCB5 and PCB11 are found in flue gas and ash from hazardous waste incineration.Of these,PCB11 has received greater attention in the literature.It has recently been consistently detected in the air,snow,soil and biota in the Arctic,evidence that PCB11 and possibly other UP-PCB congeners are global contaminants.Ice core measurements dating from 1957 to 2009 of PCBs in Svalbard reveal PCB11 presence throughout that period,indicating historic presence in the Arctic before being a focus of research elsewhere.Other UP-PCB need to be more fully investigated,especially from thermal sources.

Leveraging Learning to Improve Disaster Management Outcomes

Disaster management agencies should be exemplars of learning given the volatility of their operating environment. However, there are cognitive, social, and organizational barriers that prevent these organizations from learning. The purpose of this article is to use the Caribbean Disaster and Emergency Management Agency(CDEMA) as an example of an organization that achieves double-loop learning in spite of known barriers. This research shows significant learning variations in the CDEMA organization from the regional to the national level. The results demonstrate that the CDEMA Coordinating Unit and a few national member agencies achieve double-loop learning, while the opposite is true for many national disaster offices. Analysis of this variation is one contribution to the disaster management and organizational learning literature. The article also suggests that organizational culture is an important precursor to learning and adds a much needed case example to the management and learning literature. The study ends with a proposal for future research in the area of disaster management, culture and learning, and propositions for national disaster offices to consider in order to enhance double-loop learning.

Haplotype analysis for Irish ancestry

Forensic haplotype analysis of the male Y chromosome is currently used to establish the number of male donors in sexual assaults,the number of male bleeders in blood pattern analysis,and for ancestry correlation to genetic founder populations in biogeographic studies.In forensic laboratory applications,its primary use is for DNA profile generation with trace amounts of male DNA in the presence of excess female DNA(e.g.spermatozoa identification,male component of fingernail scrapings).Our study supports the potential use of the Y chromosome in a"dragnet"approach(most haplotypes are unique)similar to that described by Kayser in 2017 for solving a cold case sex assault and homicide in The Netherlands.Our study also researched the potential for the identification of an ancestral Irish genetic"footprint"linked to surname O'Brien and identified multiple founder group origins in Ireland and England as well as three samples with the Dal Riata(a Gaelic overkingdom)ancestral haplotype.This study indicates correlation to ancestral Irish ancestry by haplotype but not conclusively to the O'Brien surname.

Hyphenated Techniques in Liquid Chromatography and their Applications in Forensic Toxicology:A Review

Conventional analytical methods,such as gas chromatography,high performance liquid chromatography(LC),ultra-violet,and others,are ineffective in addressing the increasing number of problems in forensic toxicology.Hyphenated analytical methods,wherein the separation method are coupled or combined with spectral methods,with the help of a proper interface,are the available alternative options.The key benefits of these methods are the requisites of low limits for detection,shorter analytical time,the possibility of automation,better reproducibility,and high precision and repeatability.This review discusses on some of the hyphenated analytical methods that involve LC as the separation tool,for their most recent applications in the area of forensic toxicology focusing on the screening of drugs of abuse,the usage of alternative matrices for monitoring drug abuse,analysis of chemical warfare agents,determination of doping agents and related substances,natural toxins,environmental poisons,and examination of food produce adulteration.The incorporation of the more user-friendly LC-interfaces,such as atmospheric pressure chemical ionization,and electrospray ionization in the LC-mass spectrometry has increased the popularity of this technique tremendously among scientists of different disciplines.Hyphenated approaches have extremely low constraints regarding the identification and quantification,and offer high reproducibility,with unparalleled potential.

Troponin and Its Applications in Forensic Science

Troponin is used as the part of today's therapeutic sciences,but is also used in forensics.Studies on troponin and its use in forensic medicine have been retrieved from systematic internet search of databases"PubMed","Google Scholar","Medline,"and"Science Direct"with the last search performed in December 2019.A total of 38 publications have been reviewed that met the study criteria and have been cited in this article.Discussions on troponin often relate to its valuable attributes and particularly to its handiness as a diagnostic marker for different coronary heart disease.More specifically,it is a sensitive and specific indicators of damage to the heart muscle(myocardium)."Troponin was established in toxicological examinations as a biomarker of cardiovascular injury induced by drugs.Troponin degrades in a regular and predictable fashion and could be a reliable marker for determining the time and cause of death.In this review,the author outlines the potential application of troponin in forensic science.