Changes in the ceIl membrane of Lactobacillus bulgaricus during storage following freeze-drying

The mechanism of inactivation of freeze-dried Lactobacillus bulgaricus during storage in maltodextrin under controlled humidity was investigated. Evidence is presented supporting the hypothesis that membrane damage occurs during storage. A study on the lipid composition of the cells by gas chromatography showed a decrease in the unsaturated and saturated fatty acid content of the cell. Further evidence indicating membrane damage includes a decrease in membrane bound proton-translocating ATPase activity

Seasonal and diurnal surveillance of treated and untreated wastewater for human enteric viruses

Understanding the abundance and fate of human viral pathogens in wastewater is essential when assessing the public health risks associated with wastewater discharge to the environment. Typically, however, the microbiological monitoring of wastewater is undertaken on an infrequent basis and peak discharge events may be missed leading to the misrepresentation of risk levels. To evaluate diurnal patterns in wastewater viral loading, we undertook 3-day sampling campaigns with bi-hourly sample collection over three seasons at three wastewater treatment plants. Untreated influent was collected at Ganol and secondary-treated effluent was sampled at Llanrwst and Betws-y-Coed (North Wales, UK). Our results confirmed the presence of human adenovirus (AdV), norovirus genotypes I and II (NoVGI and NoVGII) in both influent and effluent samples while sapovirus GI (SaVGI) was only detected in influent water. The AdV titre was high and relatively constant in all samples, whereas the NoVGI, NoVGII and SaVGI showed high concentrations during autumn and winter and low counts during the summer. Diurnal patterns were detected in pH and turbidity for some sampling periods; however, no such changes in viral titres were observed apart from slight fluctuations in the influent samples. Our findings suggest that viral particle number in wastewater is not affected by daily chemical fluctuations. Hence, a grab sample taken at any point during the day may be sufficient to enumerate the viral load of wastewater effluent within an order of magnitude while four samples a day are recommended for testing wastewater influent samples

Modeling the spectral energy distribution of ULIRGs I: the radio spectra

As a constraint for new starburst/AGN models of IRAS bright galaxies we determine the radio spectra of 31 luminous and ultraluminous IRAS galaxies (LIRGs/ULIRGs). We construct the radio spectra using both new and archival data. From our sample of radio spectra we find that very few have a straight power-law slope. Although some sources show a flattening of the radio spectral slope at high frequencies the average spectrum shows a steepening of the radio spectrum from 1.4 to 22.5 GHz. This is unexpected because in sources with high rates of star formation we expect flat spectrum, free-free emission to make a significant contribution to the radio flux at higher radio frequencies. Despite this trend the radio spectral indices between 8.4 and 22.5 GHz are flatter for sources with higher values of the FIR-radio flux density ratio q, when this is calculated at 8.4 GHz. Therefore, sources that are deficient in radio emission relative to FIR emission (presumably younger sources) have a larger thermal component to their radio emission. However, we find no correlation between the radio spectral index between 1.4 and 4.8 GHz and q at 8.4 GHz. Because the low frequency spectral index is affected by free-free absorption, and this is a function of source size for a given mass of ionized gas, this is evidence that the ionized gas in ULIRGs shows a range of densities. The youngest LIRGs and ULIRGs are characterized by a larger contribution to their high-frequency radio spectra from free-free emission. However, the youngest sources are not those that have the greatest free-free absorption at low radio frequencies. The sources in which the effects of free-free absorption are strongest are instead the most compact sources. Although these have the warmest FIR colours, they are not necessarily the youngest sources.Comment: 16 pages. Submitted to A&A Re-submitted, with aesthetic improvements to the text and figure

A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points

SU5416 (Z-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone; semaxanib) is a small molecule inhibitor of the vascular endothelial growth factor receptor (VEGFR)2. A Phase I dose escalation study was performed. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used as a pharmacodynamic assessment tool. In all, 27 patients were recruited. SU5416 was administered twice weekly by fixed rate intravenous infusion. Patients were treated in sequential cohorts of three patients at 48, 65, 85 110 and 145 mg m−2. A further dose level of 190 mg m−2 after a 2-week lead in period at a lower dose was completed; thereafter, the cohort at 145 mg m−2 was expanded. SU5416 showed linear pharmacokinetics to 145 mg m−2 with a large volume of distribution and rapid clearance. A significant degree of interpatient variability was seen. SU5416 was well tolerated, by definition a maximum-tolerated dose was not defined. No reproducible changes were seen in DCE-MRI end points. Serial assessments of VEGF in a cohort of patients treated at 145 mg m−2 did not show a statistically significant treatment-related change. Parallel assessments of the impact of SU5416 on coagulation profiles in six patients showed a transient effect within the fibrinolytic pathway. Clinical experience showed that patients who had breaks of therapy longer than a week could not have treatment reinitiated at a dose of 190 mg m−2 without unacceptable toxicity. The 145 mg m−2 dose level is thus the recommended dose for future study

Finding the needle in the haystack: why high-throughput screening is good for your health

High-throughput screening is an essential component of the toolbox of modern technologies that improve speed and efficiency in contemporary cancer drug development. This is particularly important as we seek to exploit, for maximum therapeutic benefit, the large number of new molecular targets emerging from the Human Genome Project and cancer genomics. Screening of diverse collections of low molecular weight compounds plays a key role in providing chemical starting points for iterative optimisation by medicinal chemistry. Examples of successful drug discovery programmes based on high-throughput screening are described, and these offer potential in the treatment of breast cancer and other malignancies

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Cubic Virtual Ticket Agent ProjectCubic

Demand for seamless and intuitive Human-Machine Interfaces (HMI) is increasing for public transportation systems across various cities. Along with this increase in demand is the challenge of improving traveler experience for different user demographics, especially users with disabilities. The current issue is that the transportation interface is too limiting and not as intuitive for people with disabilities to use, and customer experience could improve with a better implementation of HMI methods. To solve this problem, we started by documenting and analyzing the current state of HMI methods and upcoming interactive technologies. We are currently working on implementing gesture recognition and natural language processing concepts to design a contactless virtual ticket agent. This agent will allow the transit rider to have an oral conversation with our device about tickets and passes, initiate a purchase, or find directions to a destination. With this project completed, public transportation systems will be more accessible & HMI will become clearer for Cubic\u27s transportation systems. Customer experience with transportation systems will be improved, especially for those with disabilities

Differences in ozone and particulate matter between ground level and 20 meters aloft are frequent during wintertime surface‐based temperature inversions in Fairbanks Alaska

International audienceDuring winter in Fairbanks, Alaska, fine particulate matter (PM2.5) accumulates to large concentrations at breathing level, yet little is known about atmospheric composition aloft. To investigate vertical differences of pollutants, we measured PM2.5 and ozone (O3) at 3 m and 20 m above ground level (AGL) in Fairbanks during winter (November 2019 - March 2020). We measured temperature and PM2.5 at 3 m, 6 m, 9 m and 11 m AGL on a tower to quantify surface-based temperature inversions (SBI) and near surface PM2.5 gradients. We defined SBIs as data with an 11 m minus 3 m temperature difference greater than 0.5°C. We observed the largest differences in PM2.5 and O3 when SBIs were present. During SBIs, PM2.5 accumulated to large concentrations at 3 m but to a lesser extent at 20 m, demonstrating reduced vertical mixing. During SBIs, the median PM2.5 concentration was 4.8 microgram m-3 lower at 20 m than at 3 m. When PM2.5 concentrations were large at 3 m, O3 was often completely chemically removed (titrated) but was still present at 20 m. During SBIs, the O3 mixing ratio was more than 2 nmol mol-1 larger at 20 m than at 3 m in 48% of the data. Results show that during SBIs, pollution in Fairbanks is mixed to altitudes below 20 m AGL and that the oxidation regime of the atmosphere changes from 3 m to 20 m AGL, as large differences in O3 mixing ratios were measured during SBIs