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At least 433 records · Page 24

Admission Privileges and Clinical Responsibilities for Interventional Radiologists

Although clinical involvement by interventional radiologists in the care of their patients was advocated at the inception of the specialty, the change into the clinical paradigm has been slow and patchy for reasons related to pattern of practice, financial remuneration or absence of training. The case for the value of clinical responsibilities has been made in a number of publications and the consequences of not doing so have been manifest in the erosion of the role of the interventional radiologists particularly in the fields of peripheral vascular and neuro intervention. With the recent recognition of interventional radiology (IR) as a primary specialty in the USA and the formation of IR division in the Union of European Medical Specialists and subsequent recognition of the subspecialty in many European countries, it is appropriate to relook at the issue and emphasize the need for measures to promote the clinical role of the interventional radiologist.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DNA-directed spatial assembly of photosynthetic light-harvesting proteins

This manuscript describes the surface immobilization of a light-harvesting complex to prescribed locations directed by the sequence-selective recognition of duplex DNA. In this work, an engineered light-harvesting complex (RC-LH1) derived from Rhodopseudomonas (Rps.) palustris containing the zinc finger (ZF) domain zif268 was prepared. The zif268 domain directed the binding of zfRC-LH1 to target double-stranded DNA sequences both in solution and when immobilized on lithographically defined micro-patterns. Excitation energy transfer from the carotenoids to the bacteriochlorophyll pigments within zfRC-LH1 confirmed that the functional and structural integrity of the complex is retained after surface immobilization.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Quantitative analysis of mammalian translation initiation sites by FACS -seq

An approach combining fluorescence-activated cell sorting and high-throughput DNA sequencing (FACS-seq) was employed to determine the efficiency of start codon recognition for all possible translation initiation sites (TIS) utilizing AUG start codons. Using FACS-seq, we measured translation from a genetic reporter library representing all 65,536 possible TIS sequences spanning the -6 to +5 positions. We found that the motif RYMRMVAUGGC enhanced start codon recognition and translation efficiency. However, dinucleotide interactions, which cannot be conveyed by a single motif, were also important for modeling TIS efficiency. Our dataset combined with modeling allowed us to predict genome-wide translation initiation efficiency for all mRNA transcripts. Additionally, we screened somatic TIS mutations associated with tumorigenesis to identify candidate driver mutations consistent with known tumor expression patterns. Finally, we implemented a quantitative leaky scanning model to predict alternative initiation sites that produce truncated protein isoforms and compared predictions with ribosome footprint profiling data. The comprehensive analysis of the TIS sequence space enables quantitative predictions of translation initiation based on genome sequence.

59 BASIC BIOLOGICAL SCIENCES↗

SciDAC Institute for Ultra-Scale Visualization: Activity Recognition for Ultra-Scale Visualization

Understanding the science behind ultra-scale simulations requires extracting meaning from data sets of hundreds of terabytes or more. Developing scalable parallel visualization algorithms is a key step enabling scientists to interact and visualize their data at this scale. However, at extreme scales, the datasets are so huge, there is not even enough time to view the data, let alone explore it with basic visualization methods. Automated tools are necessary for knowledge discovery -- to help sift through the information and isolate characteristic patterns, thereby enabling the scientist to study local interactions, the origin of features and their evolution in large volumes of data. These tools must be able to operate on data of this scale and work with the visualization process. In this project, we developed a framework for activity detection to allow scientists to model and extract spatio-temporal patterns from time-varying data.

97 MATHEMATICS AND COMPUTING↗

Exploring Deep Learning and Sparse Matrix Format Selection

We proposed to explore the use of Deep Neural Networks (DNN) for addressing the longstanding barriers. The recent rapid progress of DNN technology has created a large impact in many fields, which has significantly improved the prediction accuracy over traditional machine learning techniques in image classifications, speech recognitions, machine translations, and so on. To some degree, these tasks resemble the decision makings in many HPC tasks, including the aforementioned format selection for SpMV and linear solver selection. For instance, sparse matrix format selection is akin to image classification—such as, to tell whether an image contains a dog or a cat; in both problems, the right decisions are primarily determined by the spatial patterns of the elements in an input. For image classification, the patterns are of pixels, and for sparse matrix format selection, they are of non-zero elements. DNN could be naturally applied if we regard a sparse matrix as an image and the format selection or solver selection as classification problems.

97 MATHEMATICS AND COMPUTING↗

Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function.

60 APPLIED LIFE SCIENCES↗

Validation of the Sentinel-5 Precursor TROPOMI cloud data with Cloudnet, Aura OMI O 2 –O 2 , MODIS, and Suomi-NPP VIIRS

Accurate knowledge of cloud properties is essential to the measurement of atmospheric composition from space. In this work we assess the quality of the cloud data from three Copernicus Sentinel-5 Precursor (S5P) TROPOMI cloud products: (i) S5P OCRA/ROCINN_CAL (Optical Cloud Recognition Algorithm/Retrieval of Cloud Information using Neural Networks;Clouds-As-Layers), (ii) S5P OCRA/ROCINN_CRB (Clouds-as-Reflecting Boundaries), and (iii) S5P FRESCO-S (Fast Retrieval Scheme for Clouds from Oxygen absorption bands – Sentinel). Target properties of this work are cloud-top height and cloud optical thickness (OCRA/ROCINN_CAL), cloud height (OCRA/ROCINN_CRB and FRESCO-S), and radiometric cloud fraction (all three algorithms). The analysis combines (i) the examination of cloud maps for artificial geographical patterns, (ii) the comparison to other satellite cloud data (MODIS, NPP-VIIRS, and OMI O2–O2), and (iii) ground-based validation with respect to correlative observations (30 April 2018 to 27 February 2020) from the Cloudnet network of ceilometers, lidars, and radars. Zonal mean latitudinal variation of S5P cloud properties is similar to that of other satellite data. S5P OCRA/ROCINN_CAL agrees well with NPP VIIRS cloud-top height and cloud optical thickness and with Cloudnet cloud-top height, especially for the low (mostly liquid) clouds. For the high clouds, S5P OCRA/ROCINN_CAL cloud-top height is below the cloud-top height of VIIRS and of Cloudnet, while its cloud optical thickness is higher than that of VIIRS. S5P OCRA/ROCINN_CRB and S5P FRESCO cloud height are well below the Cloudnet cloud mean height for the low clouds but match on average better with the Cloudnet cloud mean height for the higher clouds. As opposed to S5P OCRA/ROCINN_CRB and S5P FRESCO, S5P OCRA/ROCINN_CAL is well able to match the lowest CTH mode of the Cloudnet observations. Peculiar geographical patterns are identified in the cloud products and will be mitigated in future releases of the cloud data products.

54 ENVIRONMENTAL SCIENCES↗

SU-G-JeP1-11: Feasibility Study of Markerless Tracking Using Dual Energy Fluoroscopic Images for Real-Time Tumor-Tracking Radiotherapy System

Purpose: The new real-time tumor-tracking radiotherapy (RTRT) system was installed in our institution. This system consists of two x-ray tubes and color image intensifiers (I.I.s). The fiducial marker which was implanted near the tumor was tracked using color fluoroscopic images. However, the implantation of the fiducial marker is very invasive. Color fluoroscopic images enable to increase the recognition of the tumor. However, these images were not suitable to track the tumor without fiducial marker. The purpose of this study was to investigate the feasibility of markerless tracking using dual energy colored fluoroscopic images for real-time tumor-tracking radiotherapy system. Methods: The colored fluoroscopic images of static and moving phantom that had the simulated tumor (30 mm diameter sphere) were experimentally acquired using the RTRT system. The programmable respiratory motion phantom was driven using the sinusoidal pattern in cranio-caudal direction (Amplitude: 20 mm, Time: 4 s). The x-ray condition was set to 55 kV, 50 mA and 105 kV, 50 mA for low energy and high energy, respectively. Dual energy images were calculated based on the weighted logarithmic subtraction of high and low energy images of RGB images. The usefulness of dual energy imaging for real-time tracking with an automated template image matching algorithm was investigated. Results: Our proposed dual energy subtraction improve the contrast between tumor and background to suppress the bone structure. For static phantom, our results showed that high tracking accuracy using dual energy subtraction images. For moving phantom, our results showed that good tracking accuracy using dual energy subtraction images. However, tracking accuracy was dependent on tumor position, tumor size and x-ray conditions. Conclusion: We indicated that feasibility of markerless tracking using dual energy fluoroscopic images for real-time tumor-tracking radiotherapy system. Furthermore, it is needed to investigate the tracking accuracy using proposed dual energy subtraction images for clinical cases.

60 APPLIED LIFE SCIENCES↗

Insight into a highly polymorphic endophyte isolated from the roots of the halophytic seepweed Suaeda salsa: Laburnicola rhizohalophila sp. nov. (Didymosphaeriaceae, Pleosporales)

In this work, we surveyed root endophytic fungi of the coastal halophyte Suaeda salsa and detected a population of a novel species that we described here as Laburnicola rhizohalophila sp. nov. No sexual sporulating structure was observed. Instead, it produced a large amount of thalloconidia, 0–1 transverse septa, hyaline to darkly pigmented, often peanut-shaped and sometimes dumbbell-shaped, both ends enlarged with numerous oil droplets inside the hyphal cells. Surprisingly, a high degree of phenotypic and physiological intraspecific variation (e.g., salinity tolerance, growth under different carbon:nitrogen ratios, and carbon utilization pattern) was recorded. The inoculation test indicated that the isolates could successfully infect host roots and form microsclerotia-like structures in cortical cells, a typical trait of dark septate endophytes (DSEs). Furthermore, most isolates were shown to promote host seedling growth. To evaluate conspecificity and infer its phylogenetic affinity, multiloci data including nuclear rRNA loci (ITS1 and 2, partial 28S), partial RNA Polymerase II second-largest subunit ( rpb2 ), and partial translation elongation factor-1α ( tef1 ) were characterized. Genealogical concordance phylogenetic species recognition (GCPSR) detected a genetically isolated clade of L. rhizohalophila within the Pleosporales in the Didymosphaeriaceae. Maximum likelihood phylogenetic reconstruction revealed that the endophytic fungus was genetically close to L aburnicola dactylidis but separated by a relatively long genetic distance. Our work highlights that the pleosporalean taxa might represent an underexplored reservoir of root DSEs.

59 BASIC BIOLOGICAL SCIENCES↗

Periplasmic Binding Protein Dimer Has a Second Allosteric Event Tied to Ligand Binding

Here, the ligand-induced conformational changes of periplasmic binding proteins (PBP) play a key role in the acquisition of metabolites in ATP binding cassette (ABC) transport systems. This conformational change allows for differential recognition of the ligand occupancy of the PBP by the ABC transporter. This minimizes futile ATP hydrolysis in the transporter, a phenomenon in which ATP hydrolysis is not coupled to metabolite transport. In many systems, the PBP conformational change is insufficient at eliminating futile ATP hydrolysis. Here we identify an additional state of the PBP that is also allosterically regulated by the ligand. Ligand binding to the homodimeric apo PBP leads to a tightening of the interface alpha-helices so that the hydrogen bonding pattern shifts to that of a 3 10 helix, in-turn altering the contacts and the dynamics of the protein interface so that the monomer exists in the presence of ligand.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Development of a mnemonic discrimination task using naturalistic stimuli with applications to aging and preclinical Alzheimer's disease

Most tasks test memory within the same day, however, most forgetting occurs after 24 h. Further, testing memory for simple words or objects does not mimic real-world memory experiences. We designed a memory task showing participants video clips of everyday kinds of experiences, including positive, negative, and neutral stimuli, and tested memory immediately and 24 h later. During the memory test, we included repeated and similar stimuli to tax both target recognition and lure discrimination ability. Participants’ memory was worse after 24 h, especially the ability to discriminate similar stimuli. Emotional videos were better remembered when tested immediately, however, after 24 h we find gist versus detail trade-offs in emotional forgetting. We also applied this paradigm to a sample of cognitively normal older adults that also underwent amyloid and tau PET imaging. We found that older adults performed worse on the task compared to young adults. While both young and older adults showed similar patterns of forgetting of repeated emotional and neutral clips, older adults showed preserved neutral compared to emotional discrimination after 24 h. Further, lure discrimination performance correlated with medial temporal lobe tau in older adults with preclinical Alzheimer’s disease. These results suggest factors such as time between encoding and retrieval, emotion, and similarity influence memory performance and should be considered when examining memory performance for an accurate picture of memory function and dysfunction.

59 BASIC BIOLOGICAL SCIENCES↗

CD23 is a glycan-binding receptor in some mammalian species

CD23, the low-affinity IgE receptor found on B lymphocytes and other cells, contains a C-terminal lectin-like domain that resembles C-type carbohydrate-recognition domains (CRDs) found in many glycan-binding receptors. In most mammalian species, the CD23 residues required to form a sugar-binding site are present, although binding of CD23 to IgE does not involve sugars. Solid-phase binding competition assays, glycoprotein blotting experiments, and glycan array analysis employing the lectin-like domains of cow and mouse CD23 demonstrate that they bind to mannose, GlcNAc, glucose, and fucose and to glycoproteins that bear these sugars in nonreducing terminal positions. Crystal structures of the cow CRD in the presence of α-methyl mannoside and GlcNAcβ1–2Man reveal that a range of oligosaccharide ligands can be accommodated in an open binding site in which most interactions are with a single terminal sugar residue. Although mouse CD23 shows a pattern of monosaccharide and glycoprotein binding similar to cow CD23, the binding is weaker. In contrast, no sugar binding was observed in similar experiments with human CD23. The absence of sugar-binding activity correlates with accumulation of mutations in the gene for CD23 in the primate lineage leading to humans, resulting in loss of key sugar-binding residues. These results are consistent with a role for CD23 in many species as a receptor for potentially pathogenic microorganisms as well as IgE. However, the ability of CD23 to bind several different ligands varies between species, suggesting that it has distinct functions in different organisms.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Neuroplastic Response After Radiation Therapy for Pediatric Brain Tumors: A Pilot Study

Purpose: Clinically effective measurement of cognitive toxicity from photon radiation therapy (XRT) should be accurate, sensitive, and specific. This pilot study tested translational findings on phasic changes in children's memory systems that are sensitive and insensitive to toxic XRT effects to identify a possible neuroplastic effect. Methods and Materials: Memory processes were prospectively tested before XRT and at 3 later time points up to 2 years in 35 children with mixed primary brain tumors who had not experienced recurrence. Memory processes were verbal-semantic, visual-semantic, and visual-perceptual, including accuracy, speed to recall, encoding, retrieval, and recognition. The mixed-effects model included time (to estimate slope), covariates (age, tumor locus, XRT field, and medications) as fixed effects, and individual random intercepts. A sensitivity analysis examined the influence of XRT dose to the hippocampi on memory. Results: Retrieval from long-term verbal-semantic memory declined 2 months after completing XRT, as seen in adults, and was lowest at 1 year, which was delayed in comparison with adults. Double dissociation from visual-perceptual memory at baseline and 2 months was found, consistent with adults. Recovery was demonstrated 2 years after XRT. Patterns were unchanged when dose to hippocampus was included in the model. Conclusions: Verbal and semantic long-term retrieval is specifically sensitive to XRT-related cognitive dysfunction, without effect on visual-perceptual memory. Children reached nadir in XRT-sensitive memory 1 year after XRT and recovered by 2 years, which is later than that observed in adults. The protracted period of post-XRT injury may represent the maturation of the human hippocampus and white matter into late adolescence.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Automated Threat Recognition For Aviation Security Applications

We have developed a framework for automated threat recognition (ATR) of explosive threat materials for both single-energy and dual-energy X-ray CT systems. Under this framework, two different types of ATR have been developed. The first type of ATR employs supervised machine learning with statistical characterization of target materials for threat identification training. The reliance only on statistical characterization information for threat training uniquely enables this style of ATR to adapt quickly to evolving threats. The second type of ATR employs deep learning through convolutional neural networks. Convolutional neural networks are attractive due to their human-like capacity for learning and strong ability to identify trends and patterns. Although this method is more powerful than the first type, it requires large amounts of training data and therefore is less agile. Each ATR performs threat characterization at the voxel neighborhood level. This approach avoids the use of threat shape as a detection criterion, which is prohibited by DHS and TSA guidelines.

97 MATHEMATICS AND COMPUTING↗

Encoding of Promiscuity in an Aminoglycoside Acetyltransferase

Aminoglycoside antibiotics are a large family of antibiotics that can be divided into two distinct classes on the basis of the substitution pattern of the central deoxystreptamine ring. Although aminoglycosides are chemically, structurally, and topologically diverse, some aminoglycoside-modifying enzymes (AGMEs) are able to inactivate as many as 15 aminoglycosides from the two main classes, the kanamycin- and neomycin-based antibiotics. In this paper, we present the crystal structure of a promiscuous AGME, aminoglycoside-N3-acetyltransferase-IIIb (AAC-IIIb), in the apo form, in binary drug (sisomicin, neomycin, and paromomycin) and coenzyme A (CoASH) complexes, and in the ternary neomycin–CoASH complex. These data provide a structural framework for interpretation of the thermodynamics of enzyme–ligand interactions and the role of solvent in the recognition of ligands. In combination with the recent structure of an AGME that does not have broad substrate specificity, these structures allow for the direct determination of how antibiotic promiscuity is encoded in some AGMEs.

60 APPLIED LIFE SCIENCES↗

Mapping the Morphology of DNA on Carbon Nanotubes in Solution Using X-ray Scattering Interferometry

Single-walled carbon nanotubes (SWCNTs) with adsorbed single-stranded DNA (ssDNA) are applied as sensors to investigate biological systems, with potential applications ranging from clinical diagnostics to agricultural biotechnology. Unique ssDNA sequences render SWCNTs selectively responsive to target analytes such as (GT)n-SWCNTs recognizing the neuromodulator, dopamine. It remains unclear how the ssDNA conformation on the SWCNT surface contributes to functionality, as observations have been limited to computational models or experiments under dehydrated conditions that differ substantially from the aqueous biological environments in which the nanosensors are applied. We demonstrate a direct mode of measuring in-solution ssDNA geometries on SWCNTs via X-ray scattering interferometry (XSI), which leverages the interference pattern produced by AuNP tags conjugated to ssDNA on the SWCNT surface. We employ XSI to quantify distinct surface-adsorbed morphologies for two (GT) n ssDNA oligomer lengths (n = 6, 15) that are used on SWCNTs in the context of dopamine sensing and measure the ssDNA conformational changes as a function of ionic strength and during dopamine interaction. Here, we show that the shorter oligomer, (GT) 6 , adopts a more periodically ordered ring structure along the SWCNT axis (inter-ssDNA distance of 8.6 ± 0.3 nm), compared to the longer (GT) 15 oligomer (most probable 5'-to-5' distance of 14.3 ± 1.1 nm). During molecular recognition, XSI reveals that dopamine elicits simultaneous axial elongation and radial constriction of adsorbed ssDNA on the SWCNT surface. Our approach using XSI to probe solution-phase morphologies of polymer-functionalized SWCNTs can be applied to yield insights into sensing mechanisms and inform future design strategies for nanoparticle-based sensors.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Structural determinants of nuclear export signal orientation in binding to exportin CRM1

The Chromosome Region of Maintenance 1 (CRM1) protein mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure. The plasticity of the CRM1-NES interaction is not well understood, as there are many NES sequences that seem incompatible with structures of the NES-bound CRM1 groove. Crystal structures of CRM1 bound to two different NESs with unusual sequences showed the NES peptides binding the CRM1 groove in the opposite orientation (minus) to that of previously studied NESs (plus). A comparison of minus and plus NESs identified structural and sequence determinants for NES orientation. The binding of NESs to CRM1 in both orientations results in a large expansion in NES consensus patterns and therefore a corresponding expansion of potential NESs in the proteome.

59 BASIC BIOLOGICAL SCIENCES↗

Investigation about relationships between the symmetries of ferroelectric crystal Ca{sub 0.28}Ba{sub 0.72}Nb{sub 2}O{sub 6} and second-harmonic patterns

The broadband quasi-phase matching (QPM) process in a uniaxial ferroelectric crystal Ca{sub 0.28}Ba{sub 0.72}Nb{sub 2}O{sub 6} (CBN-28) was demonstrated with the second-harmonic wavelength range from 450 nm to 650 nm, and the relationship between the symmetries of CBN-28 and the second-harmonic patterns was experimentally and theoretically investigated based on the random anti-parallel domains in the crystal and QPM conditions. The dependences of frequency-doubled patterns on the wavelength and anisotropy of the nonlinear crystal were also studied, and the frequency-doubled photons were found to be trapped on circles. By analyzing the light-matter interacting Hamiltonians, the trapping force for second-harmonic photons was found to be centripetal and tunable by the fundamental lasers, and the variation tendencies of the rotational velocity of second-harmonic generation photons could also be predicated. The results indicate that the CBN-28 ferroelectric crystal is a promising nonlinear optical material for the generation of broadband frequency-doubled waves, and the analysis on centripetal force based on the interaction Hamiltonians may provide a novel recognition for the investigation of QPM process to be further studied.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗