1,020 research outputs found

    Evaluating Attenuated Total Reflectance Fourier Transform Infrared to Identify and Delineate Gravesoil Post-Exhumation of a Murine Carrion

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    Understanding remains removal and relocation provides intelligence aiding in the accuracy of post-mortem interval estimation (PMI), formulating a timeline of events in subsequent death inquests. The quantitative longevity of the chemical cadaver decomposition island (CDI) regarding translocation of remains is particularly pertinent at historical and cold-case crime scenes. This study aimed to track shifts in subsurface soil physicochemistry in simulation burial microcosms where adult Mus musculus were utilised as human cadaver proxies. Soil samples were taken from the microcosms over 170 days post-exhumation of 8, 16, 24 and 32 days of initial burial (n=3). Physicochemical properties of the gravesoil were obtained non-destructively using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. ATR-FTIR spectra highlighted temporal delineation of microcosms on the basis time-since-removal of remains. Changes in the both symmetrical and asymmetrical CH2 wagging present at -~2920 cm-1 and ~2850 cm-1 , indicative of aliphatic chain lipids, were prolonged significantly in post-exhumation soils when the carrion was removed after 3 and 4 weeks of burial

    Evaluating attenuated total reflectance infrared and near infrared spectroscopy for classifying M. musculus grave soil in the presence of clothing material

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    Objectives: Common methods utilised for establishing the time elapsed for unattended death scenes rely on physical atrophy. Predicting postmortem interval (PMI) relies on visual inspection, total body scoring and rigor mortis where the three are influenced by biotic and/or abiotic variables. These variables include the presence of different types of textiles that affect the cadaver decomposition island (CDI) in the type of fluids and decomposition products in the surrounding environment. Therefore, this work explores the impact of clothing material on the formation and timeline of CDI in simulated grave soil using attenuated total reflectance Fourier transform infrared (ATR-FTIR) and near infrared (NIR) spectroscopy. Materials and Methods: Grave soil evaluated in this study included samples that had carrions under different conditions including: (1) unwrapped carrions, (2) wrapped carrions with three types of fabric being cotton, polyester and viscose. Samples were stored in boxes and monitored over 170 days for environmental factors (temperature, pH, humidity) and for physicochemical properties. Physicochemical properties were determined using ATR-FTIR and NIR spectroscopy. Wrapped and unwrapped soil samples were measured frequently at weekly intervals through glass vials for NIR spectra or by placing 1-2 mg of soil on the diamond accessory for ATR-FTIR spectra. In both cases, spectra were exported into Matlab 2019a where spectral interpretation and analysis were applied. Spectral interpretation comprised comparing the absorbances obtained for soil samples against the reported literature. Spectral analysis involved applying principal component analysis (PCA) that informed about patterns in the absorbances of soils both unwrapped and wrapped with different fabrics. Results: Both ATR-FTIR and NIR spectra informed about the chemical and physical profile of soil samples with unwrapped and wrapped cadavers. ATR-FTIR spectra highlighted shifts in both O-H stretching and bending bands at ~3300 cm-1 and ~1640 cm-1, respectively. Grave soil associated with M. musculus exhibited increased intensity at ~1250 cm-1 C-O-C ester stretching, indicative of volatile organic compounds that produce the characteristic smell of death. This peak was delayed significantly in response to wrapping in various textiles. Although bands relating to lipid (~1760 cm-1) and protein (1690/1680 cm-1) degradation were identified on ATR spectra from the textiles post-exhumation, these were not identified in the respective soil samples. Both symmetrical and asymmetrical CH2 wagging present at 2920 cm-1 and 2850 cm-1, suggested the presence of saturated and unsaturated fatty acids. NIR spectra also highlighted temporal changes in -OH bonds (1420 nm). Although not highlighted by ATR, amides and amine secondary and tertiary overtone profiles, were detectable in soil samples associated with decomposing M. musculus between 1000 and 1200 nm. When PCA was applied to both types of spectra, it showed its ability to distinguish between the different types of fabric that the cadavers had been wrapped with. Conclusions: Our findings showed that ATR-FTIR and NIR spectroscopy offered a non-destructive approach to understand the decomposition of cadaver remains in soil. Moreover, both techniques informed about the impact about different textiles on the formation of CDI. In this respect, the presence of textiles has delayed CDI formation. By combining both techniques with PCA, soil samples could be classified indicating to the type of fabric the cadaver had been wrapped with

    Bacterial Detectives: Investigating fabric presence and type on grave soil necrobiome dynamics

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    The unique and ubiquitous nature of the microbiome has garnered interest for forensic applications such as: geolocation, bodily fluid and personal item identification. Upon death the successional necrobiome can provide considerable insights. Measurement of subsurface grave soil has proven a successful means of discriminating burial locale and postmortem (PMI) / postburial (PBI) interval. Further knowledge development is pertinent to address current gaps prior to implementation to formulate forensic models. One key variable is the presence and type of carrion-associated fabric, with the understanding that clothing influences decomposition atrophy, entomology and movement of cadaveric fluids. We collected grave soil from 15 ex situ laboratory-based murine decomposition microcosms associated with three different fabric types over 170 days. Restriction fragment length polymorphism (RFLP) quantified with Hill ecological indices (0D=species richness, 1D, 2D=species diversity) highlighted temporal clustering of soils, irrespective of fabric type when principal component analysis (PCA) was applied. However, control soils could not be consistently discriminated. High-resolution metabarcoding (16S rRNA) recorded temporal class – and order-level bacterial markers at class such as, Spirochaetia (10.2%), Sphingobacteria (5.2%), Legionellales (1.5%), and Saprospirales (1.8%) at PBI=32 of advanced decay. Family and genus level taxonomic resolution highlighted measurable increases in Pseudomonas PBI=8 in cotton- (8.7%) and polyester- (18.3%) wrapped carrion microcosms. Thus, fabric presence and type were reflected in the simulation grave soil necrobiome. However, this study questions the efficacy of Mus musculus or mammalian proxies and simulation decomposition microcosms due to ethical constraints, in conducting applicable forensic research in lieu of human taphonomy facilities

    Inter-domain dynamics in the chaperone SurA and multi-site binding to its outer membrane protein clients

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    The periplasmic chaperone SurA plays a key role in outer membrane protein (OMP) biogenesis. E. coli SurA comprises a core domain and two peptidylprolyl isomerase domains (P1 and P2), but its mechanisms of client binding and chaperone function have remained unclear. Here, we use chemical cross-linking, hydrogen-deuterium exchange mass spectrometry, single-molecule FRET and molecular dynamics simulations to map the client binding site(s) on SurA and interrogate the role of conformational dynamics in OMP recognition. We demonstrate that SurA samples an array of conformations in solution in which P2 primarily lies closer to the core/P1 domains than suggested in the SurA crystal structure. OMP binding sites are located primarily in the core domain, and OMP binding results in conformational changes between the core/P1 domains. Together, the results suggest that unfolded OMP substrates bind in a cradle formed between the SurA domains, with structural flexibility between domains assisting OMP recognition, binding and release

    Normal modes and discovery of high-order cross-frequencies in the DBV white dwarf GD 358

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    We present a detailed mode identification performed on the 1994 Whole Earth Telescope (WET) run on GD 358. The results are compared with that obtained for the same star from the 1990 WET data. The two temporal spectra show very few qualitative differences, although amplitude changes are seen in most modes, including the disappearance of the mode identified as k=14 in the 1990 data. The excellent coverage and signal-to-noise ratio obtained during the 1994 run lead to the secure identification of combination frequencies up to fourth order, i.e. peaks that are sums or differences of up to four parent frequencies, including a virtually complete set of second-order frequencies, as expected from harmonic distortion. We show how the third-order frequencies are expected to affect the triplet structure of the normal modes by back-interacting with them. Finally, a search for â„“=2 modes was unsuccessful, not verifying the suspicion that such modes had been uncovered in the 1990 data set

    When will 'open science' become simply 'science'?

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    Open science describes the practice of carrying out scientific research in a completely transparent manner, and making the results of that research available to everyone. Isn’t that just ‘science’

    A phase I study of the safety and tolerability of olaparib (AZD2281, KU0059436) and dacarbazine in patients with advanced solid tumours

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    BACKGROUND: Poly adenosine diphosphate (ADP)-ribose polymerase (PARP) is essential in cellular processing of DNA damage via the base excision repair pathway (BER). The PARP inhibition can be directly cytotoxic to tumour cells and augments the anti-tumour effects of DNA-damaging agents. This study evaluated the optimally tolerated dose of olaparib (4-(3--4-fluorophenyl) methyl-1(2H)-one; AZD2281, KU0059436), a potent PARP inhibitor, with dacarbazine and assessed safety, toxicity, clinical pharmacokinetics and efficacy of combination treatment. PATIENTS AND METHODS: Patients with advanced cancer received olaparib (20-200 mg PO) on days 1-7 with dacarbazine (600-800 mg m(-2) IV) on day 1 (cycle 2, day 2) of a 21-day cycle. An expansion cohort of chemonaive melanoma patients was treated at an optimally tolerated dose. The BER enzyme, methylpurine-DNA glycosylase and its substrate 7-methylguanine were quantified in peripheral blood mononuclear cells. RESULTS: The optimal combination to proceed to phase II was defined as 100 mg bd olaparib with 600 mg m(-2) dacarbazine. Dose-limiting toxicities were neutropaenia and thrombocytopaenia. There were two partial responses, both in patients with melanoma. CONCLUSION: This study defined a tolerable dose of olaparib in combination with dacarbazine, but there were no responses in chemonaive melanoma patients, demonstrating no clinical advantage over single-agent dacarbazine at these doses

    The ethics of digital well-being: a multidisciplinary perspective

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    This chapter serves as an introduction to the edited collection of the same name, which includes chapters that explore digital well-being from a range of disciplinary perspectives, including philosophy, psychology, economics, health care, and education. The purpose of this introductory chapter is to provide a short primer on the different disciplinary approaches to the study of well-being. To supplement this primer, we also invited key experts from several disciplines—philosophy, psychology, public policy, and health care—to share their thoughts on what they believe are the most important open questions and ethical issues for the multi-disciplinary study of digital well-being. We also introduce and discuss several themes that we believe will be fundamental to the ongoing study of digital well-being: digital gratitude, automated interventions, and sustainable co-well-being

    Is DRE essential for the follow up of prostate cancer patients? A prospective audit of 194 patients

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    BACKGROUND: Prostate cancer follow up forms a substantial part of the urology outpatient workload. Nurse led prostate cancer follow up clinics are becoming more common. Routine follow-up may involve performing DRE, which may require training. OBJECTIVES: The aim of this audit was to assess the factors that influenced the change in the management of prostate cancer patients during follow up. This would allow us to pave the way towards a protocol driven follow up clinic led by nurse specialists without formal training in DRE. RESULTS: 194 prostate cancer patients were seen over a period of two months and all the patients had DRE performed on at least one occasion. The management was changed in 47 patients. The most common factor influencing this change was PSA trend. A change in DRE findings influenced advancement of the clinic visit in 2 patients. CONCLUSIONS: PSA is the most common factor influencing change in the management of these patients. Nurse specialists can run prostate cancer follow-up clinics in parallel to existing consultant clinics and reserve DRE only for those patients who have a PSA change or have onset of new symptoms. However larger studies are required involving all the subgroups of patients to identify the subgroups of patients who will require DRE routinely

    Induction of epigenetic variation in Arabidopsis by over-expression of DNA METHYLTRANSFERASE1 (MET1)

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    Epigenetic marks such as DNA methylation and histone modification can vary among plant accessions creating epi-alleles with different levels of expression competence. Mutations in epigenetic pathway functions are powerful tools to induce epigenetic variation. As an alternative approach, we investigated the potential of over-expressing an epigenetic function, using DNA METHYLTRANSFERASE1 (MET1) for proof-of-concept. In Arabidopsis thaliana, MET1 controls maintenance of cytosine methylation at symmetrical CG positions. At some loci, which contain dense DNA methylation in CG- and non-CG context, loss of MET1 causes joint loss of all cytosines methylation marks. We find that over-expression of both catalytically active and inactive versions of MET1 stochastically generates new epi-alleles at loci encoding transposable elements, non-coding RNAs and proteins, which results for most loci in an increase in expression. Individual transformants share some common phenotypes and genes with altered gene expression. Altered expression states can be transmitted to the next generation, which does not require the continuous presence of the MET1 transgene. Long-term stability and epigenetic features differ for individual loci. Our data show that over-expression of MET1, and potentially of other genes encoding epigenetic factors, offers an alternative strategy to identify epigenetic target genes and to create novel epi-alleles
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