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At least 739 records · Page 41

Automatic Classification of Biological Targets in a Tidal Channel Using a Multibeam Sonar

Multibeam sonars are widely used for environmental monitoring of fauna at marine renewable energy sites. However, they can rapidly accrue vast volumes of data, which poses a challenge for data processing. Here, using data from a deployment in a tidal channel with peak currents of 1–2 m s –1 , we demonstrate the data-reduction benefits of real-time automatic classification of targets detected and tracked in multibeam sonar data. First, we evaluate classification capabilities for three machine learning algorithms: random forests, support vector machines, and k-nearest neighbors. For each algorithm, a hill-climbing search optimizes a set of hand-engineered attributes that describe tracked targets. Here, the random forest algorithm is found to be most effective—in postprocessing, discriminating between biological and nonbiological targets with a recall rate of 0.97 and a precision of 0.60. In addition, 89% of biological targets are correctly classified as either seals, diving birds, fish schools, or small targets. Model dependence on the volume of training data is evaluated. Second, a real-time implementation of the model is shown to distinguish between biological targets and nonbiological targets with nearly the same performance as in postprocessing. From this, we make general recommendations for implementing real-time classification of biological targets in multibeam sonar data and the transferability of trained models.

16 TIDAL AND WAVE POWER↗

SU-F-T-638: Is There A Need For Immobilization in SRS?

Purpose: Frameless Stereotactic radiosurgery (SRS) is increasingly used in the clinic. Cone-Beam CT (CBCT) to simulation-CT match has replaced the 3-dimensional coordinate based set up using a stereotactic localizing frame. The SRS frame however served as both a localizing and immobilizing device. We seek to measure the quality of frameless (mask based) and frame based immobilization and evaluate its impact on target dose. Methods: Each SRS patient was set up by kV on-board imaging (OBI) and then fine-tuned with CBCT. A second CBCT was done at treatment-end to ascertain intrafraction motion. We compared pre- vs post-treatment CBCT shifts for both frameless and frame based SRS patients. CBCT to sim-CT fusion was repeated for each patient off-line to assess systematic residual image registration error. Each patient was re-planned with measured shifts to assess effects on target dose. Results: We analyzed 11 patients (12 lesions) treated with frameless SRS and 6 patients (11 lesions) with a fixed frame system. Average intra-fraction iso-center positioning errors for frameless and frame-based treatments were 1.24 ± 0.57 mm and 0.28 ± 0.08 mm (mean ± s.d.) respectively. Residual error in CBCT registration was 0.24 mm. The frameless positioning uncertainties led to target dose errors in Dmin and D95 of 15.5 ± 18.4% and 6.6 ± 9.1% respectively. The corresponding errors in fixed frame SRS were much lower with Dmin and D95 reduced by 4.2 ± 6.5% and D95 2.5 ± 3.8% respectively. Conclusion: Frameless mask provides good immobilization with average patient motion of 1.2 mm during treatment. This exceeds MRI voxel dimensions (∼0.43mm) used for target delineation. Frame-based SRS provides superior patient immobilization with measureable movement no greater than the background noise of the CBCT registration. Small lesions requiring submm precision are better served with a frame based SRS.

60 APPLIED LIFE SCIENCES↗

Robust, versatile DNA FISH probes for chromosome-specific repeats in Caenorhabditis elegans and Pristionchus pacificus

Repetitive DNA sequences are useful targets for chromosomal fluorescence in situ hybridization. We analyzed recent genome assemblies of Caenorhabditis elegans and Pristionchus pacificus to identify tandem repeats with a unique genomic localization. Based on these findings, we designed and validated sets of oligonucleotide probes for each species targeting at least 1 locus per chromosome. These probes yielded reliable fluorescent signals in different tissues and can easily be combined with the immunolocalization of cellular proteins. Synthesis and labeling of these probes are highly cost-effective and require no hands-on labor. The methods presented here can be easily applied in other model and nonmodel organisms with a sequenced genome.

59 BASIC BIOLOGICAL SCIENCES↗

Critical configurations of fundamental range networks.

A range network is defined to consist of ground stations and targets where only distances between the two sets of points are observed. Such a network is said to be fundamental when only those six constraints are used that are needed to define the coordinate system for an adjustment. When ground stations or targets have certain configurations, a unique adjustment in terms of coordinates may be impossible, even when the number of observations is sufficient and the coordinate system is uniquely defined. Such configurations, resulting in the singular solutions, are said to be critical. Attention is therefore focused on singular solutions rather than on numerical problems in some ill-conditioned systems of fundamental range networks. The critical configurations are presented in two separate groups. The first deals with ground stations lying all in a plane and the second deals with ground stations generally distributed. The two kinds of problems require different mathematical treatments and lead to quite different conclusions.

Blaha, G.↗

A formalism for cosmic ray propagation studies

The continuity equation for cosmic ray propagation is used to derive a set of linear equations interrelating the fluxes of multiply charged nuclei as observed at any particular part of the galaxy. The derivation leads to model independent definitions for cosmic ray storage time, mean density of target nuclei and effective mass traversed. The set of equations form a common framework for comparisons of theories and observations. As an illustration, it is shown that there exists a large class of propagation models which give the same result as the exponential path length model. The formalism is shown to accommodate dynamic as well as equilibrium models of production and propagation.

Golden, R. L.↗

A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl{sub 4})-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl{sub 4} (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl{sub 4}. We observed that combined treatment with CCl{sub 4} and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis.

60 APPLIED LIFE SCIENCES↗

Pose Classification Using Three-Dimensional Atomic Structure-Based Neural Networks Applied to Ion Channel–Ligand Docking

The identification of promising lead compounds showing pharmacological activities toward a biological target is essential in early stage drug discovery. With the recent increase in available small-molecule databases, virtual high-throughput screening using physics-based molecular docking has emerged as an essential tool in assisting fast and cost-efficient lead discovery and optimization. However, the best scored docking poses are often suboptimal, resulting in incorrect screening and chemical property calculation. We address the pose classification problem by leveraging data-driven machine learning approaches to identify correct docking poses from AutoDock Vina and Glide screens. To enable effective classification of docking poses, we present two convolutional neural network approaches: a three-dimensional convolutional neural network (3D-CNN) and an attention-based point cloud network (PCN) trained on the PDBbind refined set. We demonstrate the effectiveness of our proposed classifiers on multiple evaluation data sets including the standard PDBbind CASF-2016 benchmark data set and various compound libraries with structurally different protein targets including an ion channel data set extracted from Protein Data Bank (PDB) and an in-house KCa3.1 inhibitor data set. Our experiments show that excluding false positive docking poses using the proposed classifiers improves virtual high-throughput screening to identify novel molecules against each target protein compared to the initial screen based on the docking scores.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

High performance context switching for virtualized FPGA accelerators

A hardware context manager in a field-programmable gate array (FPGA) device includes configuration logic configured to program one or more programming regions in the FPGA device based on configuration data for implementing a target configuration of the one or more programming regions. Context management logic in the hardware context manager is coupled with the configuration logic and saves a first context corresponding to the target configuration by retrieving first state information from the set of one or more programming regions, where the first state information is generated based on the target configuration, and storing the retrieved first state information in a context memory. The context management logic restores the first context by transferring the first state information from the context memory to the one or more programming regions, and causing the configuration logic to program the one or more programming regions based on the configuration data.

42 ENGINEERING↗

SU-F-T-289: MLC Fluence Sonogram Based Delivery Quality Assurance for Bilateral Breast Irradiation

Purpose: Performing DQA for Bilateral (B-L) breast tomotherapy is a challenging task due to the limitation of any commercially available detector array or film. Aim of this study is to perform DQA for B-L breast tomotherapy plan using MLC fluence sinogram. Methods: Treatment plan was generated on Tomotherapy system for B-L breast tumour. B-L breast targets were given 50.4 Gy prescribed over 28 fractions. Plan is generated with 6 MV photon beam & pitch was set to 0.3. As the width of the total target is 39 cm (left & right) length is 20 cm. DQA plan delivered without any phantom on the mega voltage computed tomography (MCVT) detector system. The pulses recorded by MVCT system were exported to the delivery analysis software (Tomotherapy Inc.) for reconstruction. The detector signals are reconstructed to a sonogram and converted to MLC fluence sonogram. The MLC fluence sinogram compared with the planned fluence sinogram. Also point dose measured with cheese phantom and ionization chamber to verify the absolute dose component Results: Planned fluence sinogram and reconstructed MLC fluence sinogram were compared using Gamma metric. MLC positional difference and intensity of the beamlet were used as parameters to evaluate gamma. 3 mm positional difference and 3% beamlet intensity difference were used set for gamma calculation. A total of 26784 non-zero beamlets were included in the analysis out of which 161 beamlets had gamma more than 1. The gamma passing rate found to be 99.4%. Point dose measurements were within 1.3% of the calculated dose. Conclusion: MLC fluence sinogram based delivery quality assurance performed for bilateral breast irradiation. This would be a suitable alternate for large volume targets like bilateral breast, Total body irradiation etc. However conventional method of DQA should be used to validate this method periodically.

60 APPLIED LIFE SCIENCES↗

Functionalized Single-Walled Carbon Nanotube-Based Fuel Cell Benchmarked Against US DOE 2017 Technical Targets

Chemically modified single-walled carbon nanotubes (SWNTs) with varying degrees of functionalization were utilized for the fabrication of SWNT thin film catalyst support layers (CSLs) in polymer electrolyte membrane fuel cells (PEMFCs), which were suitable for benchmarking against the US DOE 2017 targets. Use of the optimum level of SWNT -COOH functionality allowed the construction of a prototype SWNT-based PEMFC with total Pt loading of 0.06 mg Pt /cm 2 - well below the value of 0.125 mg Pt /cm 2 set as the US DOE 2017 technical target for total Pt group metals (PGM) loading. This prototype PEMFC also approaches the technical target for the total Pt content per kW of power (<0.125 g PGM /kW) at cell potential 0.65 V: a value of 0.15 g Pt /kW was achieved at 80°C/22 psig testing conditions, which was further reduced to 0.12 g Pt /kW at 35 psig back pressure.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

A Multiplexed Quantitative Analysis of Germline Single Amino Acid Variants by Targeted Proteomics in Nondepleted Human Plasma

Single amino acid variants (SAAVs) in protein sequences are often a direct result of single-nucleotide polymorphisms (SNPs). Certain germline SAAVs have shown biological relevance in different disease conditions but lack precise quantification in circulation, which could hinder functional investigations and progress in biomarker development. Here, we have developed a multiplexed liquid chromatography-selected reaction monitoring (LC-SRM) assay that monitors 5 wild-type and variant peptide pairs (Complement Factor B: CFB-R32Q/R32W, Clusterin: CLU-N317H, Fetuin B: FETUB-K360R, and Kininogen: KNG1-L212P) in nondepleted human plasma. The assay was optimized for imprecision, linearity, stability, and calibration assessments with CVs of under 20%. The wild-type and variant peptide pairs were characterized in a set of healthy individual plasma samples. These target identifications were also validated by SNP genotyping with more than 99% accuracy. For all protein targets, we observed significantly lower concentrations of WT species in the presence variant peptides. In CFB, the concentration of R32Q was significantly lower than its counterpart R32W variant and WT species. Furthermore, our results distinguished phenotypes of homozygosity and heterozygosity of the SAAV presence through direct concentration level characterization. These findings provide some insights into how SAAVs affect quantitative assessments of target peptides. The assay demonstrates a platform for proteogenomic analyses with potential applications in both research and clinical settings.

genetics↗

Correlation between Chiral Modifier Adsorption and Enantioselectivity in Hydrogenation Catalysis

Infrared absorption spectroscopy performed in situ at the solid–liquid interface revealed that the adsorption on platinum supported catalysts of 1-(1-naphthyl)-ethylamine, which is used as a chiral modifier in hydrogenation catalysis, occurs through the amine group, not the aromatic ring as is widely believed. In this work, comparisons were performed against a set of related modifier compounds with targeted substitutions to help identify the key moiety involved in the adsorption. It was determined that neither naphthalene-based modifiers without amine groups nor those with tertiary amine moieties are capable of adsorbing on the metal surface to any significant extent. A direct correlation was also found between the ability of the amines to adsorb on the platinum surface and their performance as chiral modifiers that impart enantioselectivity to the hydrogenation of α-keto esters such as ethyl pyruvate.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Direct SERDS sensing of molecular biomarkers in plants under field conditions

Molecular biomarkers such as microRNAs (miRNAs) play important roles in regulating various developmental processes in plants. Understanding these pathways will help bioengineer designing organisms for efficient biomass accumulation. Current methods for RNA analysis require sample extraction and multi-step sample analysis, hindering work in field studies. Recent work in the incorporation of nanomaterials for plant bioengineering research is leading the way of an agri-tech revolution. As an example, surface-enhanced Raman scattering (SERS)–based sensors can be used to monitor RNA in vivo. However, the use of SERS in the field has been limited due to issues with observing Raman signal over complex background. To this end, shifted-excitation Raman difference spectroscopy (SERDS) offers an effective solution to extract the SERS signal from high background based on a physical approach. In this manuscript, we report the first application of SERDS on SERS sensors. We investigated this technique on SERS sensor developed for the detection of a microRNA biomarker, miR858. We tested the technique on in vitro samples and validated the technique by detecting the presence of exogenous miR858 in plants directly under ambient light in a growth chamber. The possibility of moving the detection of nucleic acid targets outside the constraints of laboratory setting enables numerous important bioengineering applications. Finally, such applications can revolutionize biofuel production and agri-tech through the use of nanotechnology-based monitoring of plant growth, plant health, and exposure to pollution and pathogens.

09 BIOMASS FUELS↗

Head and Neck Margin Reduction With Adaptive Radiation Therapy: Robustness of Treatment Plans Against Anatomy Changes

Purpose: We set out to investigate loss of target coverage from anatomy changes in head and neck cancer patients as a function of applied safety margins and to verify a cone beam computed tomography (CBCT)–based adaptive strategy with an average patient anatomy to overcome possible target underdosage. Methods and Materials: For 19 oropharyngeal cancer patients, volumetric modulated arc therapy treatment plans (2 arcs; simultaneous integrated boost, 70 and 54.25 Gy; 35 fractions) were automatically optimized with uniform clinical target volume (CTV)–to–planning target volume margins of 5, 3, and 0 mm. We applied b-spline CBCT–to–computed tomography (CT) deformable registration to allow recalculation of the dose on modified CT scans (planning CT deformed to daily CBCT following online positioning) and dose accumulation in the planning CT scan. Patients with deviations in primary or elective CTV coverage >2 Gy were identified as candidates for adaptive replanning. For these patients, a single adaptive intervention was simulated with an average anatomy from the first 10 fractions. Results: Margin reduction from 5 mm to 3 mm to 0 mm generally led to an organ-at-risk (OAR) mean dose (D{sub mean}) sparing of approximately 1 Gy/mm. CTV shrinkage was mainly seen in the elective volumes (up to 10%), likely related to weight loss. Despite online repositioning, substantial systematic errors were present (>3 mm) in lymph node CTV, the parotid glands, and the larynx. Nevertheless, the average increase in OAR dose was small: maximum of 1.2 Gy (parotid glands, D{sub mean}) for all applied margins. Loss of CTV coverage >2 Gy was found in 1, 3, and 7 of 73 CTVs, respectively. Adaptive intervention in 0-mm plans substantially improved coverage: in 5 of 7 CTVs (in 6 patients) to <2 Gy of initially planned. Conclusions: Volumetric modulated arc therapy head and neck cancer treatment plans with 5-mm margins are robust for anatomy changes and show a modest increase in OAR dose. Margin reduction improves OAR sparing with approximately 1 Gy/mm at the expense of target coverage in a subgroup of patients. Patients at risk of CTV underdosage >2 Gy in 0-mm plans may be identified early in treatment using dose accumulation. A single intervention with an average anatomy derived from CBCT effectively mitigates discrepancies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Additive manufacturing of AISI M2 tool steel by binder jetting (BJ): Investigation of microstructural and mechanical properties

The presented research demonstrates for the first time the successful processing of AISI M2 tool steel by binder jetting, a promising additive manufacturing technique capable of producing complex shapes with minimal residual stresses and isotropic properties. The optimal printing parameters were explored by varying processing parameters such as the binder saturation (45 %–105 %), binder set time (0 to 10 s), targeted bed temperature (50–60 °C), oscillator (2600–2750 rpm), recoater (20–28 mm/s), and roller speeds (200–300 rpm). Microstructural characterization and evaluation of mechanical properties of binder jetted parts were performed using x-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) to study their chemical composition, powder morphology, microstructure, carbide morphologies, relative density, hardness, compressive strength, and ductility. Two powder sizes (5 and 10 μm) were used, and sintering was performed at varying temperatures (1270, 1280, and 1300 °C) and durations (60 and 120 min), followed by a furnace, air, and water cooling. An optimum hardness of ~970 HV was obtained when parts were sintered at 1270 °C for 60 min, followed by water quenching. Impressive compressive strength of ~ 3580 MPa was observed in the sample sintered at 1280 °C for 60 min duration, followed by air cooling. Furnace-cooled parts showed the highest density of ~95 %, whereas the relative density of air- and water-cooled parts varied between ~91 to 93.50 %, respectively. The microstructure of sintered samples revealed the formation of M 6 C stable carbide, M 2 C metastable carbide, MC as a secondary carbide, and a-Fe matrix, which contributed to the observed increase in mechanical properties.

36 MATERIALS SCIENCE↗

Measured and projected beam backgrounds in the Belle II experiment at the SuperKEKB collider

The Belle II experiment at the SuperKEKB electron–positron collider aims to collect an unprecedented data set of 50 ab -1 to study CP -violation in the B -meson system and to search for Physics beyond the Standard Model. SuperKEKB is already the world’s highest-luminosity collider. In order to collect the planned data set within approximately one decade, the target is to reach a peak luminosity of 6 x 10 35 cm −2 s −1 by further increasing the beam currents and reducing the beam size at the interaction point by squeezing the betatron function down to β $^*_y$ = 0.3 mm. To ensure detector longevity and maintain good reconstruction performance, beam backgrounds must remain well controlled. We report on current background rates in Belle II and compare these against simulation. We find that a number of recent refinements have significantly improved the background simulation accuracy. Finally, we estimate the safety margins going forward. We predict that backgrounds should remain high but acceptable until a luminosity of at least 2.8 x 10 35 cm −2 s −1 is reached for β $^*_y$ = 0.6 mm. At this point, the most vulnerable Belle II detectors, the Time-of-Propagation (TOP) particle identification system and the Central Drift Chamber (CDC), have predicted background hit rates from single-beam and luminosity backgrounds that add up to approximately half of the maximum acceptable rates.

Detector background↗

Faster solutions to the interdiction defense problem using suboptimal solutions

The interdiction defense (ID) problem solves a defender-attacker-defender model where the defender and attacker share the same set of components to harden and target. Here, we build upon the best response intersection (BRI) algorithm by developing the BRI with suboptimal solutions (BRI-SS) algorithm to solve the ID problem. The BRI-SS algorithm utilizes off-the-shelf optimization solvers that return suboptimal solutions at no additional computation cost. We derive novel cuts from suboptimal solutions, reducing the number of iterations required for the algorithm to converge while maintaining optimality guarantees. We also present a heuristic that utilizes all obtained suboptimal solutions to select the next defense to evaluate at each iteration. We perform computational experiments applied to power grid interdiction on standard test cases. Our results demonstrate that the BRI-SS algorithm consistently outperforms the BRI algorithm across all test cases.

Computer science↗

Sesquiterpene dimmer (DSF-27) inhibits the release of neuroinflammatory mediators from microglia by targeting spleen tyrosine kinase (Syk) and Janus kinase 2 (Jak2): Two major non-receptor tyrosine signaling proteins involved in inflammatory events

Non-receptor protein tyrosine kinases (NRPTKs)-dependent inflammatory signal transduction cascades play key roles in immunoregulation. However, drug intervention through NRPTKs-involved immunoregulation mechanism in microglia (the major immune cells of the central nervous system) has not been widely investigated. A main aim of the present study is to elucidate the contribution of two major NRPTKs (Syk and Jak2) in neuroinflammation suppression by a bioactive sesquiterpene dimmer (DSF-27). We found that LPS-stimulated BV-2 cells activated Syk and further initiated Akt/NF-κB inflammatory pathway. This Syk-dependent Akt/NF-κB inflammatory pathway can be effectively ameliorated by DSF-27. Moreover, Jak2 was activated by LPS, which was followed by transcriptional factor Stat3 activation. The Jak2/Stat3 signal was suppressed by DSF-27 through inhibition of Jak2 and Stat3 phosphorylation, promotion of Jak/Stat3 inhibitory factors PIAS3 expression, and down-regulation of ERK and p38 MAPK phosphorylation. Furthermore, DSF-27 protected cortical and mesencephalic dopaminergic neurons against neuroinflammatory injury. Taken together, our findings indicate NRPTK signaling pathways including Syk/NF-κB and Jak2/Stat3 cascades are potential anti-neuroinflammatory targets in microglia, and may also set the basis for the use of sesquiterpene dimmer as a therapeutic approach for neuroinflammation via interruption of these pathways. - Highlights: • Sesquiterpene dimmer DSF-27 inhibits inflammatory mediators' production in microglia. • Syk-dependent Akt/NF-κB pathway is important for DSF-27's anti-inflammation activity. • Jak2/Stat3 pathway is important for DSF-27's anti-inflammation activity. • Jak2/Stat3 signaling pathway is partly regulated by ERK and p38 MAPKs and PIAS3. • DSF-27 protects neurons against microglia-mediated neuroinflammatory injury.

60 APPLIED LIFE SCIENCES↗