Simple quantitative assessment of the outdoor versus indoor airborne transmission of viruses and COVID-19.

In this paper we develop a simple model of the inhaled flow rate of aerosol particles of respiratory origin i.e. that have been exhaled by other people. A connection is made between the exposure dose and the probability of developing an airborne disease. This allows a simple assessment of the outdoor versus indoor risk of contamination to be made in a variety of meteorological situations. It is shown quantitatively that for most cases, the outdoor risk is orders of magnitude less than the indoor risk and that it can become comparable only for extremely specific meteorological and topographical situations. It sheds light on various observations of COVID-19 spreading in mountain valleys with temperature inversions while at the same time other areas are much less impacted.

Determining the water content of nominally anhydrous minerals at the nanometre scale.

The amount and distribution of water in nominally anhydrous minerals (NAMs) are usually determined by Fourier-transform infrared spectroscopy. This method is limited by the spot size of the beam to the study of samples with dimensions greater than a few micrometers. Here, we demonstrate the potential of using photoinduced force microscopy for the measurement of water in NAMs with samples sizes down to the nanometer scale with a study of water concentration across grain boundaries in forsterite. This development will enable the study of water speciation and diffusion in small-grained rock matrixes and allow a determination of the influence of nanoscale heterogeneity on the incorporation of water to NAMs.

Computer-aided manufacturing and focused ion beam technology enable machining of complex micro- and nano-structures.

We present a novel framework for the fabrication of geometrically complex structures at the micro- and nano-scale which relies on the synergy of integrated computer-aided design and manufacturing systems (CAD/CAM) and focused ion beam (FIB) technology in a scanning electron microscope. Here we utilise industry standard G-code syntax, for the first time, to FIB machining by designing geometries with CAD, defining machining strategies and exporting G-codes with CAM and generating a coordinate list-based beam path by using a custom-built interpreter program. This allows the fabrication of complex structures from CAD models using syntax which is readily understood in the general fabrication industry. The use of G-code allows optimization of the beam path towards a reduction of beam blanking operations and tracing of contours, leading to minimized re-deposition of material. We give a detailed description of the method, use an application example to demonstrate advantages and prospects of the approach and provide the free and open-source interpreter program CAM2FIB for application of this method. We contrast and compare various existing available milling strategies and demonstrate the versatility of G-code based programming.

Modelling of ultraviolet light inactivation kinetics of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, Clostridium difficile spores and murine norovirus on fomite surfaces.

AIMS: Quantitative data on the doses needed to inactivate micro-organisms on fomites are not available for ultraviolet applications. The goal of this study was to determine the doses of UV light needed to reduce bacteria and murine norovirus (MNV) on hard surface fomites through experimentation and to identify appropriate models for predicting targeted levels of reduction. METHODS AND RESULTS: Stainless steel and Formica laminate coupons were selected as they are common surfaces found in healthcare settings. Test organisms included methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Clostridium difficile and MNV. The fomites were inoculated with 105 -107 bacteria or virus and exposed to a range of UV doses. The order of resistance to UV irradiation was virus, bacterial spore and vegetative cell. The best fitting inactivation curves suggested nonlinear responses to increasing doses after a 3-4 log reduction in the test organisms. The average UV doses required for a 3 log reduction in the C. difficile, MRSA and VRE were 16 000, 6164 and 11 228 (mJ-s cm-2 ) for stainless steel, respectively, and 16 000, 11 727 and 12 441 (mJ-s cm-2 ) for Formica laminate, respectively. CONCLUSIONS: Higher UV light doses are required to inactivate bacteria and viruses on hard surfaces than in suspension. Greater doses are needed to inactivate bacterial spores and MNV compared to vegetative bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Quantitative data and models on UV light doses needed to inactivate bacteria and MNV on hard surfaces are now available. The generalizable results of this study can be used to estimate required UV dosages to achieve targeted levels of inactivation based on estimated levels of contamination or to support quantitative microbial risk assessments.

Transmission Kikuchi diffraction versus electron back-scattering diffraction: A case study on an electron transparent cross-section of TWIP steel.

The present case study compares transmission Kikuchi diffraction (TKD) with electron back-scattering diffraction (EBSD) on the same area of an electron transparent cross-section of a twinning induced plasticity steel. While TKD expectedly provides better clarity of internal defect substructures in the band contrast map, EBSD returns orientation data that approaches the quality of the TKD map. This was rationalised by Monte Carlo simulations of the electron energy spreads, which showed that due to the geometry-based compromises associated with adapting a conventional EBSD detector (which is off-axis with respect to the incident electron beam) to TKD, a broadening in the electron energy distribution of the forward-scattered electrons collected on the detector phosphor screen, is unavoidable. In this circumstance, the values of the full-widths at half-maximum of the energy distributions for TKD and EBSD are of the same order. It follows that EBSD on electron transparent cross-sections may be a viable alternative to TKD when: (i) conventional EBSD detectors are adapted to TKD and, (ii) sample microstructures comprise features whose sizes do not mandate the application of TKD.

Effect of Tempol on the prevention of irradiation-induced mucositis in miniature pigs.

OBJECTIVE: The goals of this study were to (i) establish a useful miniature pig (minipig) model for irradiation-induced oral mucositis and (ii) evaluate the effect of Tempol to prevent its development. METHODS AND MATERIALS: Minipigs were irradiated with 6 Gy for five consecutive days targeting the entire oral cavity. To prevent radiation damage, minipigs were treated with 30 mg kg-1 Tempol 10 min before irradiation (n = 4), while the radiation-alone group was similarly injected with saline (n = 4). Lesions were graded using an oral mucositis score and visual inspection every 3 days, and biopsy of multiple sites was performed at day 18. Weight and chest and abdominal circumferences were measured every 3 days. RESULTS: Lesions began about 12 days after the first irradiation fraction and healed about 30 days after irradiation. Epithelial thickness was calculated on the lingual and buccal mucosa on the 18th day after the first irradiation fraction. Tempol provided modest protection from ulceration after irradiation using this treatment strategy. CONCLUSIONS: This study established a useful large animal model for irradiation-induced oral mucositis and showed modest beneficial effects of Tempol in limiting tissue damage. The latter finding may be potentially valuable in preventing oral mucositis in patients receiving irradiation for head and neck cancers.

First in-flight synchrotron X-ray absorption and photoemission study of carbon soot nanoparticles.

Many studies have been conducted on the environmental impacts of combustion generated aerosols. Due to their complex composition and morphology, their chemical reactivity is not well understood and new developments of analysis methods are needed. We report the first demonstration of in-flight X-ray based characterizations of freshly emitted soot particles, which is of paramount importance for understanding the role of one of the main anthropogenic particulate contributors to global climate change. Soot particles, produced by a burner for several air-to-fuel ratios, were injected through an aerodynamic lens, focusing them to a region where they interacted with synchrotron radiation. X-ray photoelectron spectroscopy and carbon K-edge near-edge X-ray absorption spectroscopy were performed and compared to those obtained for supported samples. A good agreement is found between these samples, although slight oxidation is observed for supported samples. Our experiments demonstrate that NEXAFS characterization of supported samples provides relevant information on soot composition, with limited effects of contamination or ageing under ambient storage conditions. The highly surface sensitive XPS experiments of airborne soot indicate that the oxidation is different at the surface as compared to the bulk probed by NEXAFS. We also report changes in soot's work function obtained at different combustion conditions.

Oxidative stress in oral diseases.

Oxidative species, including reactive oxygen species (ROS), are components of normal cellular metabolism and are required for intracellular processes as varied as proliferation, signal transduction, and apoptosis. In the situation of chronic oxidative stress, however, ROS contribute to various pathophysiologies and are involved in multiple stages of carcinogenesis. In head and neck cancers specifically, many common risk factors contribute to carcinogenesis via ROS-based mechanisms, including tobacco, areca quid, alcohol, and viruses. Given their widespread influence on the process of carcinogenesis, ROS and their related pathways are attractive targets for intervention. The effects of radiation therapy, a central component of treatment for nearly all head and neck cancers, can also be altered via interfering with oxidative pathways. These pathways are also relevant to the development of many benign oral diseases. In this review, we outline how ROS contribute to pathophysiology with a focus toward head and neck cancers and benign oral diseases, describing potential targets and pathways for intervention that exploit the role of oxidative species in these pathologic processes.

Probe current determination in analytical TEM/STEM and its application to the characterization of large area EDS detectors.

A simple procedure, which enables accurate measurement of transmission electron microscopy (TEM)/STEM probe currents using an energy loss spectrometer drift tube is described. The currents obtained are compared with those measured on the fluorescent screen to enable the losses due to secondary and backscattered electrons to be determined. The current values obtained from the drift tube allow the correction of fluorescent screen current densities to yield true current. They also enable CCD conversion efficiencies to be obtained, which in turn allows images to be calibrated in terms of electron fluence. Using probes of known current in conjunction with a NiO reference specimen enables the X-ray detector solid angle to be determined. The NiO specimen also allows a wide range of other EDS detector parameters to be obtained, including the presence of ice and carbon contamination. A range of performance characteristics are reported for two large area EDS detector systems. Many of the measurements reported herein have been automated via the use of freely available scripts for DigitalMicrograph.

A review of methods for the calculation of solution free energies and the modelling of systems in solution.

Over the past decade, pharmaceutical companies have seen a decline in the number of drug candidates successfully passing through clinical trials, though billions are still spent on drug development. Poor aqueous solubility leads to low bio-availability, reducing pharmaceutical effectiveness. The human cost of inefficient drug candidate testing is of great medical concern, with fewer drugs making it to the production line, slowing the development of new treatments. In biochemistry and biophysics, water mediated reactions and interactions within active sites and protein pockets are an active area of research, in which methods for modelling solvated systems are continually pushed to their limits. Here, we discuss a multitude of methods aimed towards solvent modelling and solubility prediction, aiming to inform the reader of the options available, and outlining the various advantages and disadvantages of each approach.

Predicting Melting Points of Organic Molecules: Applications to Aqueous Solubility Prediction Using the General Solubility Equation.

In this work we make predictions of several important molecular properties of academic and industrial importance to seek answers to two questions: 1) Can we apply efficient machine learning techniques, using inexpensive descriptors, to predict melting points to a reasonable level of accuracy? 2) Can values of this level of accuracy be usefully applied to predicting aqueous solubility? We present predictions of melting points made by several novel machine learning models, previously applied to solubility prediction. Additionally, we make predictions of solubility via the General Solubility Equation (GSE) and monitor the impact of varying the logP prediction model (AlogP and XlogP) on the GSE. We note that the machine learning models presented, using a modest number of 2D descriptors, can make melting point predictions in line with the current state of the art prediction methods (RMSE≥40 °C). We also find that predicted melting points, with an RMSE of tens of degrees Celsius, can be usefully applied to the GSE to yield accurate solubility predictions (log10 S RMSE<1) over a small dataset of drug-like molecules.

Electron impact induced fragmentation of N2H⁺ and N2D⁺.

Electron impact dissociation of protonated and deuterated nitrogen ions has been studied using a crossed beams apparatus. Absolute cross sections for dissociation channels producing N(+) and NH(+), respectively, are presented. The observations of subthreshold signals in these measurements indicate the presence of ro-vibrationally and possibly electronically excited states in the parent ions. Comparisons with other measurements are given.

CD44 is prognostic for overall survival in the NCI randomized trial on breast conservation with 25 year follow-up.

CD44 is a transmembrane glycoprotein involved in numerous cellular functions, including cell adhesion and extracellular matrix interactions. It is known to be functionally diverse, with alternative splice variants increasingly implicated as a marker for tumor-initiating stem cells associated with poor prognosis. Here, we evaluate CD44 as a potential marker of long-term breast cancer outcomes. Tissue specimens from patients treated on the National Cancer Institute 79-C-0111 randomized trial of breast conservation versus mastectomy between 1979 and 1987 were collected, and immunohistochemistry was performed using the standard isoform of CD44. Specimens were correlated with patient characteristics and outcomes. Survival analysis was performed using the log rank test. Fifty-one patients had evaluable tumor sections and available long-term clinical follow up data at a median follow up of 25.7 years. Significant predictors of OS were tumor size (median OFS 25.4 years for ≤2 cm vs. 7.5 years for >2 cm, p = 0.001), nodal status (median OS 17.2 years for node-negative patients vs. 6.7 years for node positive patients, p = 0.017), and CD44 expression (median OS 18.9 years for CD44 positive patients vs. 8.6 years for CD44 negative patients, p = 0.049). There was a trend toward increased PFS for patients with CD44 positive tumors (median PFS 17.9 vs. 4.3 years, p = 0.17), but this did not reach statistical significance. These findings illustrate the potential utility of CD44 as a prognostic marker for early stage breast cancer. Subgroup analysis in patients with lymph node involvement revealed CD44 positivity to be most strongly associated with increased survival, suggesting a potential role of CD44 in decision making for axillary management. As there is increasing interest in CD44 as a therapeutic target in ongoing clinical trials, the results of this study suggest additional investigation regarding the role CD44 in breast cancer is warranted.

Resistance exercise and lipoproteins in postmenopausal women.

The specific aims of this study were to quantify the effects of 12 weeks of resistance training, as well as a single session of resistance exercise on lipids and lipoproteins in obese, postmenopausal women. 21 obese, postmenopausal women, not on hormone replacement therapy (age=65.9 ± 0.5 yr; BMI=32.7 ± 0.8 kg/m(2)), were randomly assigned to control (n=12) and exercise (n=9) groups matched for age and BMI. For 12 weeks, 3 days/week, the exercise group performed 10 whole body resistance exercises (3 sets at 8-RM). Fasting (10 h) blood samples were collected immediately prior to and 24 h after the first and last exercise and control session. Serum was assayed for concentrations of total cholesterol, triglycerides, LDL-C, HDL-C, HDL 2-C, HDL 3-C, non-HDL-C and TC:HDL and LDL:HDL ratios. The exercise group exhibited a significant (P<0.01) improvement in muscular strength, but no change in BMI, body mass or body composition post-training. Total cholesterol, LDL-C and non-HDL-C were significantly (P<0.05) lower in the exercise compared to the control group following the 12 weeks of resistance training. Whole body resistance training provides obese, postmenopausal women a non-pharmacological approach for the reduction of lipid and lipoprotein-cholesterol concentrations.

TBI with lung dose reduction does not improve hematopoietic cell homing to BM during allogeneic transplantation.

To determine the effects of TBI dose, fractionation and lung shielding on hematopoietic stem cell homing to the BM, BM cells were extracted from tibiae and femurs of B6-green fluorescent protein (GFP) mice and transplanted into B6 mice. Recipient mice had either: (i) no radiation, (ii) single-dose TBI at 13.6 Gy, (iii) single-dose TBI at 13.6 Gy with reduced lung exposure to 0.4 Gy by shielding, (iv) split-dose TBI at 12 Gy to twice per day over 4 days or (v) split-dose TBI at 12 Gy to twice per day over 4 days with reduced lung exposure to 0.36 Gy by shielding. The last radiation exposure preceded tail vein injection by 4-6 h. Mice were killed after 18 h. The homing of GFP-positive, lineage-negative cells was not significantly improved in any irradiated group compared with control. The homing of GFP-positive, lineage-negative, Kit-positive cells was significantly worse in all irradiated groups. TBI does not improve the homing of lineage-negative donor BM cells to the recipient marrow. The homing of lineage-negative, Kit-positive donor BM cells was significantly worse following TBI, with or without lung dose reduction.

Evidence for nanoparticles in microwave-generated fireballs observed by synchrotron x-ray scattering.

The small-angle x-ray scattering method has been applied to study fireballs ejected into the air from molten hot spots in borosilicate glass by localized microwaves [V. Dikhtyar and E. Jerby, Phys. Rev. Lett. 96 045002 (2006)10.1103/PhysRevLett.96.045002]. The fireball's particle size distribution, density, and decay rate in atmospheric pressure were measured. The results show that the fireballs contain particles with a mean size of approximately 50 nm with average number densities on the order of approximately 10(9). Hence, fireballs can be considered as a dusty plasma which consists of an ensemble of charged nanoparticles in the plasma volume. This finding is likened to the ball-lightning phenomenon explained by the formation of an oxidizing particle network liberated by lightning striking the ground [J. Abrahamson and J. Dinniss, Nature (London) 403, 519 (2000)10.1038/35000525].

Evaluation of sub-microsecond recovery resonators for in vivo electron paramagnetic resonance imaging.

Time-domain (TD) electron paramagnetic resonance (EPR) imaging at 300MHz for in vivo applications requires resonators with recovery times less than 1 micros after pulsed excitation to reliably capture the rapidly decaying free induction decay (FID). In this study, we tested the suitability of the Litz foil coil resonator (LCR), commonly used in MRI, for in vivo EPR/EPRI applications in the TD mode and compared with parallel coil resonator (PCR). In TD mode, the sensitivity of LCR was lower than that of the PCR. However, in continuous wave (CW) mode, the LCR showed better sensitivity. The RF homogeneity was similar in both the resonators. The axis of the RF magnetic field is transverse to the cylindrical axis of the LCR, making the resonator and the magnet co-axial. Therefore, the loading of animals, and placing of the anesthesia nose cone and temperature monitors was more convenient in the LCR compared to the PCR whose axis is perpendicular to the magnet axis.

Heat acclimation and HSP-72 expression in exercising humans.

The purpose of this research was to determine the effect of a 7-day heat acclimation protocol on HSP-72 expression in human skeletal muscle, and to examine the relationships between molecular and physiological markers of heat acclimation. Ten recreationally active male subjects (age = 23.3 +/- 2.81 yrs, VO(2peak) = 3.85 +/- 0.11 L . min (-1)) completed a 7-day heat acclimation protocol consisting of cycling at 75 % of VO(2peak) in a hot environment (39.5 degrees C, 27 % RH). Muscle biopsies were obtained on days 1 (HTT1) and 7 (HTT2) prior to, 6 h post, and 24 h postexercise to measure HSP-72 protein via SDS-PAGE and silver staining. Core rectal temperatures (T(C)), intramuscular temperatures (T(IM)), skin temperatures (T(SK)), heart rate (HR), oxygen uptake (VO(2)), sweat rate (SR), and plasma cortisol were measured. TC, HR, and plasma cortisol were significantly lower in HTT2 than HTT1 (p < or = 0.05). No significant differences were seen for VO(2), TIM, TSK, or SR when comparing HTT2 with HTT1 (p < or = 0.05). No significant time or day x time interactions were detected for HSP-72 expression (24.48 +/- 2.55 vs. 25.04 +/- 1.43 ng/microg protein for HTT1 and HTT2, respectively, p < or = 0.05). Evidence of heat acclimation was seen at the physiological level; however, no evidence of enhanced thermotolerance at the cellular level was indicated by HSP-72 expression.

Electron and ion reactions with hexamethyldisiloxane and pentamethyldisiloxane.

The dissociative recombination of electrons with the hexamethyldisiloxane (HMDSO) cation ((CH(3))(3)Si-O-Si(CH(3))(3))(+) and the pentamethyldisiloxane cation ((CH(3))(3)Si-O-Si(CH(2))(2))(+) as well as the ion-molecule reaction between Ar(+) and HMDSO have been studied at 300 K using a flowing afterglow Langmuir probe-mass spectrometer apparatus. The rate constants for these reactions, measured directly for the first time, are, respectively, alpha(1)=1.8 x 10(-6), alpha(2)=3.6 x 10(-6) cm(3)s, and k=2.0 x 10(-9) cm(3)s with uncertainties of +/-30%. In addition, the electronic attachment to neutral HMDSO was also studied and an upper limit value of the rate constant was determined to be beta=3.3 x 10(-11) cm(3)s.