Morphological variations of explosive residue particles and implications for understanding detonation mechanisms

The possibility of recovering undetonated explosive residues following detonation events is well-known; however, the morphology and chemical identity of these condensed phase postblast particles remains undetermined. An understanding of the postblast explosive particle morphology would provide vital information during forensic examinations, allowing rapid initial indication of the explosive material to be microscopically determined prior to any chemical analyses and thereby saving time and resources at the crucial stage of an investigation. In this study, condensed phase particles collected from around the detonations of aluminized ammonium nitrate and RDX-based explosive charges were collected in a novel manner utilizing SEM stubs. By incorporating the use of a focused ion beam during analysis, for the first time it is possible to determine that such particles have characteristic shapes, sizes, and internal structures depending on the explosive and the distance from the detonation at which the particles are recovered. Spheroidal particles (10–210 μm) with microsurface features recovered following inorganic charge detonations were dissimilar to the irregularly shaped particles (5–100 μm) recovered following organic charge firings. Confirmatory analysis to conclude that the particles were indeed explosive included HPLC-MS, Raman spectroscopy, and mega-electron volt–secondary ionization mass spectrometry. These results may impact not only forensic investigations but also the theoretical constructs that govern detonation theory by indicating the potential mechanisms by which these particles survive and how they vary between the different explosive types.EPSRC Grant EP/G037264/

Sarawak Peat Characteristics and Heat Treatment

Peat layer is extensively scattered over the land of Malaysia. In Sarawak alone, peatland represents 13 percent (about 1.66 million hectares) of Sarawak’s total land area. They are present, mostly in low-lying areas; with in some areas, peat exceeding 10 m in depth. During past few decades, the demands on development of land were expanded into the swamp and deep peat areas which cannot be avoided. Thus proper management and construction practices should be emphasized, in order to overcome consequential occurrence of ground subsidence problems. The objectives of this study are to determine the characteristics of Sarawak peat, their empirical correlations as well as the effect of heat treatment on peat. The samples were taken from Matang, Batu Kawa, and Kota Samarahan sites, in Sarawak. The characteristic tests consist of degree of humidification, loss on ignition, Atterberg limit, particle density, moisture content and pH value. The results recorded high moisture content and organic content of Sarawak peat. It is also being categorized under the hemic group with pH values ranging from 3 to 4. The heat treatments with temperatures ranging from 100°C to 400°C were used on the peat samples. Samples collected were undergoing heat treatment and changes to its physical characteristic were compared with the original Sarawak peat. It was found that the heat treatments do influence the physical properties of Sarawak peat and have shown significant reduction in the compression index determined through the empirical correlations

Radiation Therapy in Addition to Gross Total Resection of Retroperitoneal Sarcoma Results in Prolonged Survival: Results from a Single Institutional Study

Purpose. Typical treatment of retroperitoneal sarcomas (RPSs) is surgery with or without radiation therapy for localized disease. With surgery alone, local failure rates are as high as 90%; this led to radiation therapy playing an important role in the treatment of RPSs. Methods. Thirty-one patients with retroperitoneal sarcoma treated with gross total resection and radiation therapy make up this retrospective analysis. Nineteen were treated preoperatively and 12 postoperatively (median dose, 59.4 Gy)—sixteen also received intraoperative radiation therapy (IORT) (median dose, 11 Gy). Patients were followed with stringent regimens, including frequent CT scans of the chest, abdomen, and pelvis. Results. With a median follow-up of 19 months (range 1–66 months), the 2-year overall survival (OS) rate is 70% (median, 52 months). The 2-year locoregional control (LRC) rate is 77% (median, 61.6 months). The 2-year distant disease free survival (DDFS) rate is 70% (median not reached). There were no differences in radiation-related acute and late toxicities among patients treated pre- versus postoperatively, whether with or without IORT. Conclusions. Compared to surgery alone, neoadjuvant or adjuvant radiation therapy offers patients with RPS an excellent chance for long-term LRC, DDS, and OS. The integration of modern treatment planning for external beam radiation therapy and IORT allows for higher doses to be delivered with acceptable toxicities

Safety and pharmacokinetics of anti-TFPI antibody (concizumab) in healthy volunteers and patients with hemophilia: a randomized first human dose trial

BACKGROUND: Prophylaxis with either intravenous (i.v.) factor VIII (FVIII) or FIX is the gold standard of care for patients with severe hemophilia. A monoclonal antibody (concizumab) targeting tissue factor pathway inhibitor (TFPI) that can be administered subcutaneously (s.c.) has the potential to alter current concepts of prophylaxis in hemophilia. OBJECTIVES: To evaluate the safety and describe the pharmacokinetics and pharmacodynamics of single-dose concizumab in healthy volunteers and patients with hemophilia A or B. METHODS: In this first human dose, phase 1, multicenter, randomized, double-blind, placebo-controlled trial escalating single i.v. (0.5-9000 μg kg(-1) ) or s.c. (50-3000 μg kg(-1) ) doses of concizumab were administered to healthy volunteers (n = 28) and hemophilia patients (n = 24). RESULTS: Concizumab had a favorable safety profile after single i.v. or s.c. administration. There were no serious adverse events and no anti-concizumab antibodies. No clinically relevant changes in platelets, prothrombin time, activated partial thromboplastin time, fibrinogen, or antithrombin were found. A dose-dependent procoagulant effect of concizumab was seen as increased levels of D-dimers and prothrombin fragment 1 + 2. Nonlinear pharmacokinetics of concizumab was observed due to target-mediated clearance. A maximum mean AUC0-∞ of 33 960 h μg mL(-1) and a maximum mean concentration of 247 μg mL(-1) was measured at the highest dose. CONCLUSIONS: Concizumab showed a favorable safety profile after i.v. or s.c. administration and nonlinear pharmacokinetics was observed due to target-mediated clearance. A concentration-dependent procoagulant effect of concizumab was observed, supporting further study into the potential use of s.c. concizumab for hemophilia treatment

Structural rearrangement of mesostructured silica nanoparticles incorporated with ZnO catalyst and its photoactivity: effect of alkaline aqueous electrolyte concentration

ZnO-incorporated mesostructured silica nanoparticles (MSN) catalysts (ZM) were prepared by the introduction of Zn ions into the framework of MSN via a simple electrochemical system in the presence of various concentrations of NH4OH aqueous solution. The physicochemical properties of the catalysts were studied by XRD, 29Si MAS NMR, nitrogen adsorption-desorption, FE-SEM, TEM, FTIR, and photoluminescence spectroscopy. Characterization results demonstrated that the alkaline aqueous electrolyte simply generated abundant silanol groups on the surface of the catalysts as a consequence of desilication to form the hierarchical-like structure of the MSN. Subsequent restructuring of the silica network by the creation of oxygen vacancies and formation of Si-O-Zn during the electrolysis, as well as formation of new Si-O-Si bonds during calcination seemed to be the main factors that enhanced the catalytic performance of photodecolorization of methyl orange. A ZM prepared in the presence of 1.0 M NH4OH (ZM-1.0) was determined to be the most effective catalyst. The catalyst displays a higher first-order kinetics rate of 3.87 × 10-1 h-1 than unsupported ZnO (1.13 × 10-1 h-1) that prepared under the same conditions in the absence of MSN. The experiment on effect of scavengers showed that hydroxyl radicals generated from the three main sources; reduced O2 at the conduction band, decomposed water at the valence band and irradiated H2O2 in the solution, are key factors that influenced the reaction. It is also noted that the recycled ZM-1.0 catalyst maintained its activity up to five runs without serious catalyst deactivation

Cytomegalovirus-Specific IL-10-Producing CD4+ T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence

CD4+ T cells support host defence against herpesviruses and other viral pathogens. We identified that CD4+ T cells from systemic and mucosal tissues of hosts infected with the β-herpesviridae human cytomegalovirus (HCMV) or murine cytomegalovirus (MCMV) express the regulatory cytokine interleukin (IL)-10. IL-10+CD4+ T cells co-expressed TH1-associated transcription factors and chemokine receptors. Mice lacking T cell-derived IL-10 elicited enhanced antiviral T cell responses and restricted MCMV persistence in salivary glands and secretion in saliva. Thus, IL-10+CD4+ T cells suppress antiviral immune responses against CMV. Expansion of this T-cell population in the periphery was promoted by IL-27 whereas mucosal IL-10+ T cell responses were ICOS-dependent. Infected Il27rα-deficient mice with reduced peripheral IL-10+CD4+ T cell accumulation displayed robust T cell responses and restricted MCMV persistence and shedding. Temporal inhibition experiments revealed that IL-27R signaling during initial infection was required for the suppression of T cell immunity and control of virus shedding during MCMV persistence. IL-27 production was promoted by type-I IFN, suggesting that β-herpesviridae exploit the immune-regulatory properties of this antiviral pathway to establish chronicity. Further, our data reveal that cytokine signaling events during initial infection profoundly influence virus chronicity

Activation of P2X7-mediated apoptosis Inhibits DMBA/TPA-induced formation of skin papillomas and cancer in mice

<p>Abstract</p> <p>Background</p> <p>The study tested the hypothesis that apoptosis can prevent and control growth of neoplastic cells. Previous studies in-vitro have shown that the pro-apoptotic P2X₇receptor regulates growth of epithelial cells. The specific objective of the present study was to understand to what degree the P2X₇system controls development and growth of skin cancer in vivo, and what cellular and molecular mechanisms are involved in the P2X₇action.</p> <p>Methods</p> <p>Skin neoplasias in mice (papillomas, followed by squamous spindle-cell carcinomas) were induced by local application of DMBA/TPA. Experiments in-vitro utilized cultured epidermal keratinocytes generated from wild-type or from P2X₇-null mice. Assays involved protein immunostaining and Western blots; mRNA real-time qPCR; and apoptosis (evaluated in situ by TUNEL and quantified in cultured keratinocytes as solubilized DNA or by ELISA). Changes in cytosolic calcium or in ethidium bromide influx (P2X₇pore formation) were determined by confocal laser microscopy.</p> <p>Results</p> <p>(a) Co-application on the skin of the P2X₇specific agonist BzATP inhibited formation of DMBA/TPA-induced skin papillomas and carcinomas. At the completion of study (week 28) the proportion of living animals with cancers in the DMBA/TPA group was 100% compared to 43% in the DMBA/TPA+BzATP group. (b) In the normal skin BzATP affected mainly P2X₇-receptor – expressing proliferating keratinocytes, where it augmented apoptosis without evoking inflammatory changes. (c) In BzATP-treated mice the degree of apoptosis was lesser in cancer than in normal or papilloma keratinocytes. (d) Levels of P2X₇receptor, protein and mRNA were 4–5 fold lower in cancer tissues than in normal mouse tissues. (e) In cultured mouse keratinocytes BzATP induced apoptosis, formation of pores in the plasma membrane, and facilitated prolonged calcium influx. (f) The BzATP-induced apoptosis, pore-formation and augmented calcium influx had similar dose-dependence for BzATP. (g) Pore formation and the augmented calcium influx were depended on the expression of the P2X₇receptor, while the BzATP-induced apoptosis depended on calcium influx. (h) The BzATP-induced apoptosis could be blocked by co-treatment with inhibitors of caspase-9 and caspase-3, but not of caspase-8.</p> <p>Conclusion</p> <p>(a) P2X₇-dependent apoptosis is an important mechanism that controls the development and progression of epidermal neoplasia in the mouse. (b) The P2X₇-dependent apoptosis is mediated by calcium influx via P2X₇pores, and involves the caspase-9 (mitochondrial) pathway. (c) The diminished pro-apoptotic effect of BzATP in mouse cancer keratinocytes is possibly the result of low expression of the P2X₇receptor. (d) Activation of P2X₇-dependent apoptosis, e.g. with BzATP could be a novel chemotherapeutic growth-preventive modality for papillomas and epithelial cancers in vivo.</p

The Dark Energy Spectroscopic Instrument: one-dimensional power spectrum from first Ly α forest samples with Fast Fourier Transform

We present the one-dimensional Ly α forest power spectrum measurement using the first data provided by the Dark Energy Spectroscopic Instrument (DESI). The data sample comprises 26 330 quasar spectra, at redshift z > 2.1, contained in the DESI Early Data Release and the first 2 months of the main survey. We employ a Fast Fourier Transform (FFT) estimator and compare the resulting power spectrum to an alternative likelihood-based method in a companion paper. We investigate methodological and instrumental contaminants associated with the new DESI instrument, applying techniques similar to previous Sloan Digital Sky Survey (SDSS) measurements. We use synthetic data based on lognormal approximation to validate and correct our measurement. We compare our resulting power spectrum with previous SDSS and high-resolution measurements. With relatively small number statistics, we successfully perform the FFT measurement, which is already competitive in terms of the scale range. At the end of the DESI survey, we expect a five times larger Ly α forest sample than SDSS, providing an unprecedented precise one-dimensional power spectrum measurement

Optimal 1D Lyα\alpha Forest Power Spectrum Estimation -- III. DESI early data

The one-dimensional power spectrum $P_{\mathrm{1D}}$ of the Ly$\alpha$ forest provides important information about cosmological and astrophysical parameters, including constraints on warm dark matter models, the sum of the masses of the three neutrino species, and the thermal state of the intergalactic medium. We present the first measurement of $P_{\mathrm{1D}}$ with the quadratic maximum likelihood estimator (QMLE) from the Dark Energy Spectroscopic Instrument (DESI) survey early data sample. This early sample of $54~600$ quasars is already comparable in size to the largest previous studies, and we conduct a thorough investigation of numerous instrumental and analysis systematic errors to evaluate their impact on DESI data with QMLE. We demonstrate the excellent performance of the spectroscopic pipeline noise estimation and the impressive accuracy of the spectrograph resolution matrix with two-dimensional image simulations of raw DESI images that we processed with the DESI spectroscopic pipeline. We also study metal line contamination and noise calibration systematics with quasar spectra on the red side of the Ly$\alpha$ emission line. In a companion paper, we present a similar analysis based on the Fast Fourier Transform estimate of the power spectrum. We conclude with a comparison of these two approaches and implications for the upcoming DESI Year 1 analysis.Comment: 23 pages, 20 figures. To be published in MNRA