Improvements of a Hard-Wall Closed Test-Section of a Subsonic Wind Tunnel for Aeroacoustic Testing

For achieving accurate aeroacoustic measurements to the aircraft industry, a low-speed wind tunnel, primarily designed for aerodynamic testing, is modified to provide lower background noise environment. Based on data from single microphone at different wind tunnel locations and microphone phased-array measurements inside the test-section, the main noise sources are identified and feasible alternatives are implemented for reducing the background noise such as new acoustically treated corner-vanes and sidewall lining located upstream the drive system. The acoustically transparent concept for the test-section is also investigated showing promising results for further improvements in the wind tunnel. Results are presented for sound pressure levels from single microphone measurements at different locations in the wind tunnel as well as from the beamforming array inside the test-section. Background noise measurements before and after improvements confirm that the ability of performing aeroacoustic tests has significantly increased with noise reduction of 5 dB inside the test-section.

Determination of Atorvastatin with Voltammetric Sensors Based on Nanomaterials

This paper presents an accurate and fast electrochemical method for atorvastatin determination in pharmaceutical products. Two screen-printed sensors, one—carbon based (SPCE) and one based on carbon nanotubes and gold nanoparticles (AuNP-CNT/SPCE) were used during the electrochemical analyses. At all experimental stages, cyclic voltammetry was employed, both for the characterization of the sensors and their electrochemical behavior, and for quantitative determinations. AuNP-CNT/SPCE has showed an extended active area, higher intensity peaks, better reversibility and lower background current than the unmodified sensor. For atorvastatin quantification, a calibration curve has been developed within the 1.2–606.25 µM concentration range. A linearity relation between the current of the anodic peak and concentration has been obtained in the range 1.2–53.33 µMfor both sensors. With the AuNP-CNT/SPCE sensor, low values of limit of detection, LOD (1.92 × 10−7 M) and limit of quantification, LOQ (6.39 × 10−7 M) have been obtained, which demonstrates the feasibility of the method of determining atorvastatin from real samples. Atorvastatin amount has been successfully determined from pharmaceutical products using AuNP-CNT/SPCE. The results were similar to the manufacturer’s specifications regarding the dosage per tablet and to the concentrations obtained by applying the FTIR spectrometric method.

Phased variants improve DLBCL minimal residual disease detection at the end of therapy.

7565 Background: Detection of circulating tumor DNA (ctDNA) has prognostic value in diverse tumors, including DLBCL. Despite uses for assessing molecular response to therapy, current methods using immunoglobulin or hybrid-capture sequencing have suboptimal sensitivity, particularly when disease-burden is low. This contributes to a high false negative rate at key milestones such as at the end of therapy (EOT; Kumar A, ASH 2020). We explored the utility of detecting multiple mutations (phased variants, PVs) on individual cell-free DNA (cfDNA) strands to improve MRD in DLBCL. Methods: We applied Phased Variant Enrichment and Detection Sequencing to track PVs from 485 specimens from 117 DLBCL patients undergoing first-line therapy. We sequenced cfDNA prior to, during, and after therapy to assess the prognostic value of MRD. We compared the performance of PhasED-Seq to current techniques, including SNV-based CAPP-Seq and duplex sequencing. Results: To establish its detection limit for ctDNA, we compared the background error-profile of of PVs and SNVs in cfDNA sequencing from healthy subjects. PV-detection by PhasED-Seq demonstrated a lower background profile than SNVs, even when considering duplex molecules (n = 12; 8.0e-7 vs 3.3e-5 and 1.2e-5; P < 0.0001). We also assessed analytical sensitivity within a ctDNA limiting dilution series from 3 patients, simulating tumor fractions from 0.1% to 0.00005% (1:2,000,000). PhasED-Seq outperformed SNV-based methods and duplex sequencing for recovery of expected tumor content below 0.01% (P < 0.0001 and P = 0.005 respectively by paired t-test). We then explored disease detection in clinical samples. We identified SNVs and PVs from pretreatment tumor or plasma and followed these variants in serial cfDNA. Using SNV-based methods, 40% and 59% of patients had undetectable ctDNA after 1 or 2 cycles (n = 82 and 88). However, 24% and 25% of these cases had detectable ctDNA by PhasED-Seq. Importantly, MRD detection by PhasED-Seq was prognostic for event-free survival even in patients with undetectable ctDNA by SNVs. We next explored the utility of PhasED-Seq at the EOT in 19 subjects, 5 of whom experienced eventual disease progression. While only 2/5 cases with progression had detectable disease at EOT using SNVs, PhasED-Seq detected all 5/5 cases. PhasED-Seq also correctly identified all patients (14/14) without clinical relapse as having no residual disease, including one patient who discontinued therapy after 1 cycle due to toxicity, but remains in remission > 5 years after this single treatment. This resulted in superior classification of patients for EFS using PVs compared with SNVs (C-statistic: 0.98 vs 0.60, P = 0.02). Conclusions: Tracking PVs results in significantly lower background rates than SNV-based approaches, enabling detection to parts per million range. PhasED-Seq improves on disease detection in DLBCL at the EOT, allowing possible MRD-driven consolidative approaches.

High-Sensitivity Raman Gas Probe for In Situ Multi-Component Gas Detection

Multiple reflection has been proven to be an effective method to enhance the gas detection sensitivity of Raman spectroscopy, while Raman gas probes based on the multiple reflection principle have been rarely reported on. In this paper, a multi-reflection, cavity enhanced Raman spectroscopy (CERS) probe was developed and used for in situ multi-component gas detection. Owing to signal transmission through optical fibers and the miniaturization of multi-reflection cavity, the CERS probe exhibited the advantages of in situ detection and higher detection sensitivity. Compared with the conventional, backscattering Raman layout, the CERS probe showed a better performance for the detection of weak signals with a relatively lower background. According to the 3σ criteria, the detection limits of this CERS probe for methane, hydrogen, carbon dioxide and water vapor are calculated to be 44.5 ppm, 192.9 ppm, 317.5 ppm and 0.67%, respectively. The results presented the development of this CERS probe as having great potential to provide a new method for industrial, multi-component online gas detection.

[11C]deschloroclozapine is an improved PET radioligand for quantifying a human muscarinic DREADD expressed in monkey brain

Previous work found that [11C]deschloroclozapine ([11C]DCZ) is superior to [11C]clozapine ([11C]CLZ) for imaging Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). This study used PET to quantitatively and separately measure the signal from transfected receptors, endogenous receptors/targets, and non-displaceable binding in other brain regions to better understand this superiority. A genetically-modified muscarinic type-4 human receptor (hM4Di) was injected into the right amygdala of a male rhesus macaque. [11C]DCZ and [11C]CLZ PET scans were conducted 2–24 months later. Uptake was quantified relative to the concentration of parent radioligand in arterial plasma at baseline (n = 3 scans/radioligand) and after receptor blockade (n = 3 scans/radioligand). Both radioligands had greater uptake in the transfected region and displaceable uptake in other brain regions. Displaceable uptake was not uniformly distributed, perhaps representing off-target binding to endogenous receptor(s). After correction, [11C]DCZ signal was 19% of that for [11C]CLZ, and background uptake was 10% of that for [11C]CLZ. Despite stronger [11C]CLZ binding, the signal-to-background ratio for [11C]DCZ was almost two-fold greater than for [11C]CLZ. Both radioligands had comparable DREADD selectivity. All reference tissue models underestimated signal-to-background ratio in the transfected region by 40%–50% for both radioligands. Thus, the greater signal-to-background ratio of [11C]DCZ was due to its lower background uptake.

Background Pressure Effects on the Performance of a 20 kW Magnetically Shielded Hall Thruster Operating in Various Configurations

The paper reports the characterization results of a 20 kW-class magnetically shielded Hall thruster in three different configurations and operating with a centrally mounted cathode. The characterization was carried out at two different pumping speeds in SITAEL’s IV10 vacuum chamber, resulting in two different background pressure levels for each tested operating point. A linear behavior of discharge current and thrust values versus the anode mass flow rate was noticed for both pumping speeds levels and for all the three configurations. In addition, the thrust and discharge current values were always found to be lower at lower background pressure levels. From the performance levels, a preliminary estimate of the ingested mass flow rates was performed, and the values were then compared to a recently developed background flow model. The results suggested that, for this thruster and in the tested operating regimes, the change in performance due to background pressure could be ascribed not only to the ingestion of external mass flow coming from the chamber but also to other physical processes caused by the flux of residual background neutrals.

AMUR AND PRIMORYE

The annual review of seismicity of Amur and Primorye based on the data of permanent seismic stations of Sakhalin branch GS RAS and the data of other Russian and foreign seismological agencies for 2014 is made. A detailed description of the seismic situation in different areas of the region is given. For the first time the Sikhote-Alin area (№5), where an earthquake of intensity I0=5 occurred, has dominated by terms of the released seismic energy level. Three tangible earthquakes were recorded in the region during the year. The most significant of them (Imax=5) earthquake occurred on April 12 at 21h22m east of Lake Khanka, in the ter-ritory of Primorye. Previously this territory was in the state of a seismic calm. A comparative analysis of the seismic situation in 2014 with the data of long-term observations is carried out. In 2014 the seismic energy of crustal earthquakes released in the region was one of the lowest for the past 15 years (2000–2014), except for 2006. The level of deep focus seismicity in 2014 also has low indicators. According to the methodology for assessing the level of seismic activity, the SOUS*09 scale, in 2014 the territory of Amur and Primorye is characterized by a lower background level of seismic activity.

Evaluation of a New 177Lu-Labeled Somatostatin Analog for the Treatment of Tumors Expressing Somatostatin Receptor Subtypes 2 and 5

Targeted radionuclide therapy of somatostatin receptor (SST)-expressing tumors is only partially addressed by the established somatostatin analogs having an affinity for the SST subtype 2 (SST2). Aiming to target a broader spectrum of tumors, we evaluated the bis-iodo-substituted somatostatin analog ST8950 ((4-amino-3-iodo)-d-Phe-c[Cys-(3-iodo)-Tyr-d-Trp-Lys-Val-Cys]-Thr-NH2), having subnanomolar affinity for SST2 and SST5, labeled with [177Lu]Lu3+ via the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). Human Embryonic Kidney (HEK) cells stably transfected with the human SST2 (HEK-SST2) and SST5 (HEK-SST5) were used for in vitro and in vivo evaluation on a dual SST2- and SST5-expressing xenografted mouse model. natLu-DOTA-ST8950 showed nanomolar affinity for both subtypes (IC50 (95% confidence interval): 0.37 (0.22–0.65) nM for SST2 and 3.4 (2.3–5.2) for SST5). The biodistribution of [177Lu]Lu-DOTA-ST8950 was influenced by the injected mass, with 100 pmol demonstrating lower background activity than 10 pmol. [177Lu]Lu-DOTA-ST8950 reached its maximal uptake on SST2- and SST5-tumors at 1 h p.i. (14.17 ± 1.78 and 1.78 ± 0.35%IA/g, respectively), remaining unchanged 4 h p.i., with a mean residence time of 8.6 and 0.79 h, respectively. Overall, [177Lu]Lu-DOTA-ST8950 targets SST2-, SST5-expressing tumors in vivo to a lower extent, and has an effective dose similar to clinically used radiolabeled somatostatin analogs. Its main drawbacks are the low uptake in SST5-tumors and the persistent kidney uptake.

Multilayer Epitaxial Graphene on Silicon Carbide: A Stable Working Electrode for Seawater Samples Spiked with Environmental Contaminants

The electrochemical response of multilayer epitaxial graphene electrodes on silicon carbide substrates was studied for use as an electrochemical sensor for seawater samples spiked with environmental contaminants using cyclic square wave voltammetry. Results indicate that these graphene working electrodes are more robust and have lower background current than either screen-printed carbon or edge-plane graphite in seawater. Identification algorithms developed using machine learning techniques are described for several heavy metals, herbicides, pesticides, and industrial compounds. Dose-response curves provide a basis for quantitative analysis.