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At least 991 records · Page 55

Optimization of the thrombin generation test components to measure potency of factor VIII concentrates

Introduction The thrombin generation test (TGT) is used both as a global haemostasis assay, and to compare activities of coagulation factor concentrates that have been spiked into patient plasma. However, TGT has not been systematically optimized to evaluate factor VIII (FVIII) product potency. Aims To improve the sensitivity of TGT to FVIII and allow a comparative analysis of the thrombin generating capacities of FVIII concentrates against reference preparations with known FVIII activity. Methods Concentrations of TGT components (analytical variables) were assessed to maximize the linearity and range of responses to the concentration of FVIII. Results We optimized the range and sensitivity of the TGT assay with respect to FVIII through the addition of FXIa to the assay. Other parameters that were adjusted, i.e. tissue factor (TF), procoagulant lipids and plasma concentrations, did not improve the ability of the assay to measure both high and very low levels of FVIII. In the optimized TF/FXIa‐activated TGT assay, all thrombin generation curve parameters were suitable for FVIII quantification, but thrombin peak height and maximal velocity demonstrated better linearity in the desired FVIII range. We found that the optimized TF/FXIa‐activated TGT has a wider range of sensitivity to FVIII than a commercially available TGT. Additionally, we demonstrated that the TF/FXIa‐activated assay performs adequately by comparing potency measurements of five commercially available FVIII products using TGT and traditional chromogenic and one‐stage clotting assays. Conclusions The optimized TGT assay can be used to quantify and compare the thrombin generating capacities of FVIII concentrates.

Jha, N. K.↗

Elongation Factor Tu Acts as a Chaperone to Activate an Antibacterial RNase Toxin

Many Gram-negative bacterial species use contact-dependent growth inhibition (CDI) systems to deliver toxic proteins into neighboring competitors. CDI + strains deploy CdiA effector proteins, which translocate their C-terminal toxin (CT) domains into target bacteria through a receptor-mediated delivery pathway. To protect against auto-intoxication, CDI + bacteria also produce CdiI immunity proteins that neutralize CT toxin activity. Here, we present the crystal structure of the CT·CdiI O32:H37 complex from Escherichia coli O32:H37. CT O32:H37 adopts the same fold as the tRNase domain of colicin D, and the nucleases share similar catalytic centers. However, unlike colicin D, which cleaves the anticodon loops of tRNA Arg isoacceptors, CT O32:H37 exhibits nonspecific RNase activity. Notably, we find that endogenous elongation factor Tu (EF-Tu) co-purifies with the over-produced CT·CdiI O32:H37 complex. Although EF-Tu does not bind stably to CT O32:H37 in the absence of CdiI O32:H37 , the translation factor is required for toxic RNase activity in vitro. AlphaFold 3 modeling and site-directed mutagenesis indicate that CT O32:H37 interacts with the N-terminal GTPase domain of EF-Tu. EF-Tu appears to stabilize residue Trp52 within the hydrophobic core of the toxin, which in turn supports the RNase active site through an unusual hydrogen-bonding interaction with the catalytic His67 residue. Furthermore, EF-Tu is hijacked as an essential co-factor to organize the toxin's catalytic center.

Nhan, Dinh Quan [University of California, Santa B↗

Exploring the role of biotic factors in regulating the spatial variability in land surface phenology across four temperate forest sites

Here, land surface phenology (LSP), the characterization of plant phenology with satellite data, is essential for understanding the effects of climate change on ecosystem functions. Considerable LSP variation is observed within local landscapes, and the role of biotic factors in regulating such variation remains underexplored. In this study, we selected four National Ecological Observatory Network terrestrial sites with minor topographic relief to investigate how biotic factors regulate intra-site LSP variability. We utilized plant functional type (PFT) maps, functional traits, and LSP data to assess the explanatory power of biotic factors for the start and end of season (SOS and EOS) variability. Our results indicate that PFTs alone explain only 0.8–23.4% of intra-site SOS and EOS variation, whereas including functional traits significantly improves explanatory power, with cross-validation correlations ranging from 0.50 to 0.85. While functional traits exhibited diverse effects on SOS and EOS across different sites, traits related to competitive ability and productivity were important for explaining both SOS and EOS variation at these sites. These findings reveal that plants exhibit diverse phenological responses to comparable environmental conditions, and functional traits significantly contribute to intra-site LSP variability, highlighting the importance of intrinsic biotic properties in regulating plant phenology.

60 APPLIED LIFE SCIENCES↗

A new upper bound for the growth factor in Gaussian elimination with complete pivoting

Abstract The growth factor in Gaussian elimination measures how large the entries of an LU factorization can be relative to the entries of the original matrix. It is a key parameter in error estimates, and one of the most fundamental topics in numerical analysis. We produce an upper bound of for the growth factor in Gaussian elimination with complete pivoting — the first improvement upon Wilkinson's original 1961 bound of .

Bisain, Ankit [Department of Mathematics Massachus↗

SU-E-P-15: Technique Factor Modulation and Reference Plane Air Kerma Rates in Response to Simulated Patient Thickness Variations for a Sample of Current Generation Fluoroscopes

Purpose: To evaluate and compare approaches to technique factor modulation and air kerma rates in response to simulated patient thickness variations for four state-of-the-art and one previous-generation interventional fluoroscopes. Methods: A polymethyl methacrylate (PMMA) phantom was used as a tissue surrogate for the purposes of determining fluoroscopic reference plane air kerma rates, kVp, mA, and spectral filtration over a wide range of simulated tissue thicknesses. Data were acquired for each fluoroscopic and acquisition dose curve within a default abdomen or body imaging protocol. Results: The data obtained indicated vendor- and model-specific variations in the approach to technique factor modulation and reference plane air kerma rates across a range of tissue thicknesses. Some vendors have made hardware advances increasing the radiation output capabilities of their fluoroscopes; this was evident in the acquisition air kerma rates. However, in the imaging protocol evaluated, all of the state-of-the-art systems had relatively low air kerma rates in the fluoroscopic low-dose imaging mode as compared to the previous-generation unit. Each of the newest-generation systems also employ copper filtration in the selected protocol in the acquisition mode of imaging; this is a substantial benefit, reducing the skin entrance dose to the patient in the highest dose-rate mode of fluoroscope operation. Conclusion: Understanding how fluoroscopic technique factors are modulated provides insight into the vendor-specific image acquisition approach and provides opportunities to optimize the imaging protocols for clinical practice. The enhanced radiation output capabilities of some of the fluoroscopes may, under specific conditions, may be beneficial; however, these higher output capabilities also have the potential to lead to unnecessarily high dose rates. Therefore, all parties involved in imaging, including the clinical team, medical physicists, and imaging vendors, must work together to ensure that adequate but not excessive radiation doses are used.

60 APPLIED LIFE SCIENCES↗

SU-E-T-362: Enhanced Dynamic Wedge Output Factors for Varian 2300CD and the Case for a Reference Database

Purpose: Dose inhomogeneity in treatment planning can be compensated using physical wedges. Enhanced dynamic wedges (EDW) were introduced by Varian to overcome some of the short comings of physical wedges. The objectives of this study were to measure EDW output factors for 6 MV and 20 MV photon energies for a Varian 2300CD. Secondly to review the literature in terms of published enhanced dynamic wedge output factors (EDWOF) for different Varian models and thereby adding credence to the case of the validity of reference databases. Methods: The enhanced dynamic wedge output factors were measured for the Varian 2300CD for both 6 MV and 20 MV photon energies. Twelve papers with published EDWOF for different Varian Linac models were found in the literature. Results: The EDWOF for 6 MV varied from 0.980 for a 5×5 cm 10 degree wedge to 0.424 for 20×20 cm 60 degree wedge. Similarly for 20 MV, the EDWOF varied from 0.986 for 5×5 cm 10 degree wedge to 0.529 for 20×20 cm 60 degree wedge. EDWOF are highly dependent on field size. Comparing our results with the published mean, we found an excellent agreement for 6 MV EDWOF with the percentage differences ranging from 0.01% to 0.57% with a mean of 0.03%. The coefficient of variation of published EDWOF ranged from 0.17% to 0.85% and 0.1% to 0.9% for the for 6 MV and 18MV photon energies respectively. This paper provides the first published EDWOF for 20 MV photon energy. In addition, we have provided the first compendium of EDWOFs for different Varian linac models. Conclusion: The consistency of EDWOF across models and institution provide further support that, a standard data set of basic photon and electron dosimetry could be established, as a guide for future commissioning, beam modeling and quality assurance purposes.

60 APPLIED LIFE SCIENCES↗

MO-F-CAMPUS-I-02: Accuracy in Converting the Average Breast Dose Into the Mean Glandular Dose (MGD) Using the F-Factor in Cone Beam Breast CT- a Monte Carlo Study Using Homogeneous and Quasi-Homogeneous Phantoms

Purpose: To investigate the accuracy in estimating the mean glandular dose (MGD) for homogeneous breast phantoms by converting from the average breast dose using the F-factor in cone beam breast CT. Methods: EGSnrc-based Monte Carlo codes were used to estimate the MGDs. 13-cm in diameter, 10-cm high hemi-ellipsoids were used to simulate pendant-geometry breasts. Two different types of hemi-ellipsoidal models were employed: voxels in quasi-homogeneous phantoms were designed as either adipose or glandular tissue while voxels in homogeneous phantoms were designed as the mixture of adipose and glandular tissues. Breast compositions of 25% and 50% volume glandular fractions (VGFs), defined as the ratio of glandular tissue voxels to entire breast voxels in the quasi-homogeneous phantoms, were studied. These VGFs were converted into glandular fractions by weight and used to construct the corresponding homogeneous phantoms. 80 kVp x-rays with a mean energy of 47 keV was used in the simulation. A total of 109 photons were used to image the phantoms and the energies deposited in the phantom voxels were tallied. Breast doses in homogeneous phantoms were averaged over all voxels and then used to calculate the MGDs using the F-factors evaluated at the mean energy of the x-rays. The MGDs for quasi-homogeneous phantoms were computed directly by averaging the doses over all glandular tissue voxels. The MGDs estimated for the two types of phantoms were normalized to the free-in-air dose at the iso-center and compared. Results: The normalized MGDs were 0.756 and 0.732 mGy/mGy for the 25% and 50% VGF homogeneous breasts and 0.761 and 0.733 mGy/mGy for the corresponding quasi-homogeneous breasts, respectively. The MGDs estimated for the two types of phantoms were similar within 1% in this study. Conclusion: MGDs for homogeneous breast models may be adequately estimated by converting from the average breast dose using the F-factor.

60 APPLIED LIFE SCIENCES↗

SU-F-I-13: Correction Factor Computations for the NIST Ritz Free Air Chamber for Medium-Energy X Rays

Purpose: The National Institute of Standards and Technology (NIST) uses 3 free-air chambers to establish primary standards for radiation dosimetry at x-ray energies. For medium-energy × rays, the Ritz free-air chamber is the main measurement device. In order to convert the charge or current collected by the chamber to the radiation quantities air kerma or air kerma rate, a number of correction factors specific to the chamber must be applied. Methods: We used the Monte Carlo codes EGSnrc and PENELOPE. Results: Among these correction factors are the diaphragm correction (which accounts for interactions of photons from the x-ray source in the beam-defining diaphragm of the chamber), the scatter correction (which accounts for the effects of photons scattered out of the primary beam), the electron-loss correction (which accounts for electrons that only partially expend their energy in the collection region), the fluorescence correction (which accounts for ionization due to reabsorption ffluorescence photons and the bremsstrahlung correction (which accounts for the reabsorption of bremsstrahlung photons). We have computed monoenergetic corrections for the NIST Ritz chamber for the 1 cm, 3 cm and 7 cm collection plates. Conclusion: We find good agreement with other’s results for the 7 cm plate. The data used to obtain these correction factors will be used to establish air kerma and it’s uncertainty in the standard NIST x-ray beams.

60 APPLIED LIFE SCIENCES↗

TU-H-CAMPUS-TeP2-04: Measurement of Stereotactic Output Factors with DNA Double-Strand Breaks

Purpose: Radiotherapy treatment is specified by radiation dose prescriptions, but biological DNA damage actually controls treatment effectiveness. It is impractical to directly measure dose in the clinic, so we measure quantities, such as collected charge, and calculate the relationship to dose. At small fields, such as those in stereotactic radiosurgery (SRS), charged-particle equilibrium (CPE) breaks down and the accuracy of the measurement for delivered dose decreases. By measuring DNA double-strand breaks (DSB) directly, we believe treatment accuracy could improve by providing a more meaningful measurement. Methods: A DNA dosimeter, consisting of magnetic streptavidin beads attached to 4 kilobase pair DNA strands labeled with biotin and fluorescein amidite (FAM) on opposing ends, was suspended in phosphate-buffered saline (PBS). Twenty µL samples were placed in plastic micro-capillary tubes inside a water tank setup and irradiated with 10 cm, 3 cm, 1.25 cm, 0.75 cm, and 0.5 cm radiation field sizes, where the three smallest sizes were cones. After irradiation, the dosimeters were mechanically separated into beads (intact DNA) and supernatant (broken DNA/FAM) using a magnet. The fluorescence was read and the probability of DSB was calculated. This was used to calculate the output factor for an SRS beam and compared to that measured using a diode detector. Results: The output factors relative to a 10 cm field were 0.89±0.07, 0.76±0.08, 0.59±0.04, and 0.78±0.12 for the field sizes of 3 cm, 1.25 cm, 0.75 cm, and 0.5 cm, respectively. Some of the diode measurements do not fall within these uncertainties. Conclusion: This was the first attempt to measure output factors in a water tank with the DNA dosimeter. Although differences compared to the diode were observed, the uncertainty analysis ignored systematic errors. For future work, we will repeat this experiment to quantify and correct systematic errors, such as those caused by positional alignment and sample contamination. This work was funded in part by CPRIT (RP140105).

60 APPLIED LIFE SCIENCES↗

Energy filtering–induced ultrahigh thermoelectric power factors in Ni 3 Ge

Traditional thermoelectric materials rely on low thermal conductivity to enhance their efficiency but suffer from inherently limited power factors. Innovative pathways to optimize electronic transport are thus crucial. Here, we achieve ultrahigh power factors in Ni 3 Ge-based systems through an unconventional thermoelectric materials design principle. When overlapping flat and dispersive bands are engineered to the Fermi level, charge carriers can undergo intense interband scattering, yielding an energy filtering effect similar to what has long been predicted in certain nanostructured materials. Via a multistep DFT-based screening method developed here, we find a family of L1 2 -ordered binary compounds with ultrahigh power factors up to 11 mW m −1 K −2 near room temperature, which are driven by an intrinsic phonon-mediated energy filtering mechanism. Our comprehensive experimental and theoretical study of these intriguing materials paves the way for understanding and designing high-performance scattering-tuned metallic thermoelectrics.

Science & Technology - Other Topics↗

Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy

In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. Thus, a better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events. We identified a specific subset of monocytes that express tissue factor (TF), persist after virological suppression, and trigger the coagulation cascade by activating factor X. This subset of monocytes expressing TF had a distinct gene signature with up-regulated innate immune markers and evidence of robust production of multiple proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor–α (TNF-α), and IL-6, ex vivo and in vitro upon lipopolysaccharide stimulation. We validated our findings in a nonhuman primate model, showing that TF-expressing inflammatory monocytes were associated with simian immunodeficiency virus (SIV)–related coagulopathy in the progressive [pigtail macaques (PTMs)] but not in the nonpathogenic (African green monkeys) SIV infection model. Last, Ixolaris, an anticoagulant that inhibits the TF pathway, was tested and potently blocked functional TF activity in vitro in HIV and SIV infection without affecting monocyte responses to Toll-like receptor stimulation. Strikingly, in vivo treatment of SIV-infected PTMs with Ixolaris was associated with significant decreases in D-dimer and immune activation. These data suggest that TF-expressing monocytes are at the epicenter of inflammation and coagulation in chronic HIV and SIV infection and may represent a potential therapeutic target.

60 APPLIED LIFE SCIENCES↗

Activities and risk factors associated with fall-related injuries among US Army soldiers

Introduction Falls/near falls are the second leading cause of hospitalisation and outpatient visits among US Army soldiers. While numerous studies have evaluated fall-related or near fall-related injuries among elderly adults, few have evaluated this association among young adults. The objective of this study is to describe the characteristics and risk factors associated with fall-related or near fall-related injuries among male US Army soldiers. Methods This is a cross-sectional study of male US Army Airborne Division soldiers (n=5187). Electronic surveys captured demographic, lifestyle, physical training (PT), fitness and injury data during spring/summer of 2016. Multiple logistic regression was used to identify independent risk factors of fall-related or near fall-related injuries, adjusting for potential confounders. Results Primary findings indicated that activities and risk factors associated with fall-related or near fall-related injuries among soldiers included younger age (≤35 years), holding a job that required minimal lifting activities, slower 2-mile run times and not running during personal PT. Conclusions The findings from this study suggest that male US Army soldiers and other physically active men may benefit from (1) obtaining and/or maintaining higher aerobic endurance and muscular strength, and (2) training focused on preventing fall-related injuries during PT, road marching and sports/recreational activities. Moreover, prevention strategies and education should further target younger soldiers (≤35 years old), as younger age is not modifiable.

General & Internal Medicine↗

A Relaxed Physical Factorization Preconditioner for Mixed Finite Element Coupled Poromechanics

In this work, we introduce a relaxed physical factorization (RPF) preconditioner for the efficient iterative solution of the linearized algebraic system arising from the mixed finite element discretization of coupled poromechanics equations. The preconditioner is obtained by using a proper factorization of the $3\times3$ block matrix and setting a relaxation parameter $\alpha$. The preconditioner is inspired by the relaxed dimensional factorization introduced by Benzi et al. [J. Comput. Phys., 230 (2011), pp. 6185--6202; Comput. Methods Appl. Mech. Engrg., 300 (2016), pp. 129--145]. A stable algorithm is advanced to compute the optimal value of $\alpha$, along with a lower bound to control the possible ill-conditioning of the $\alpha$ dependent inner blocks. Lastly, numerical experiments in both theoretical benchmarks and real-world applications are presented and discussed to investigate the RPF properties, performance, and robustness.

97 MATHEMATICS AND COMPUTING↗

The structure of the nucleon: Elastic electromagnetic form factors

Precise proton and neutron form factor measurements at Jefferson Lab, using spin observables, have recently made a significant contribution to the unraveling of the internal structure of the nucleon. Accurate experimental measurements of the nucleon form factors are a test-bed for understanding how the nucleon's static properties and dynamical behavior emerge from QCD, the theory of the strong interactions between quarks. There has been enormous theoretical progress, since the publication of the Jefferson Lab proton form factor ratio data, aiming at reevaluating the picture of the nucleon. We will review the experimental and theoretical developments in this field and discuss the outlook for the future.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Feasibility studies of time-like proton electromagnetic form factors at $\overline{\rm P}$ANDA at FAIR

Simulation results for future measurements of electromagnetic proton form factors at $\overline{\rm P}$ANDA (FAIR) within the PandaRoot software framework are reported. The statistical precision with which the proton form factors can be determined is estimated. The signal channel p¯p → e + e – is studied on the basis of two different but consistent procedures. The suppression of the main background channel, i.e. p¯p → π + π – , is studied. Furthermore, the background versus signal efficiency, statistical and systematical uncertainties on the extracted proton form factors are evaluated using two different procedures. The results are consistent with those of a previous simulation study using an older, simplified framework. Furthermore, a slightly better precision is achieved in the PandaRoot study in a large range of momentum transfer, assuming the nominal beam conditions and detector performance.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Brief Announcement: Communication Optimal Sparse LU Factorization for Planar Matrices

We introduce a new parallel algorithm for solving sparse LU factorization of planar matrices, which commonly arise in the finite element method for 2D PDEs. Existing scalable methods, such as the multifrontal approach with subtree-to-subcube mapping by Gupta et al. [1] and right-looking with 3D mapping by Sao et al. [2] fail to achieve optimal communication costs for these matrices. Our new algorithm combines 3D mapping and subtree-to-subcube mapping to minimize communication costs while allowing trade-offs between extra memory and reduced communication. We demonstrate that our proposed algorithm attains the communication lower bound up to a factor of O(log log n) in the memory-optimal case and up to a factor of O(log P) in the memory-independent case for an n-dimensional planar sparse matrix on P processors.

Sao, Piyush↗

An Effective Method to Accurately Calculate the Phase Space Factors for β - β - Decay

Accurate calculations of the electron phase space factors are necessary for reliable predictions of double-beta decay rates and for the analysis of the associated electron angular and energy distributions. We present an effective method to calculate these phase space factors that takes into account the distorted Coulomb field of the daughter nucleus, yet it allows one to easily calculate the phase space factors with good accuracy relative to the most exact methods available in the recent literature.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

HPC-NMF: A High-Performance Parallel Algorithm for Nonnegative Matrix Factorization

NMF is a useful tool for many applications in different domains such as topic modeling in text mining, background separation in video analysis, and community detection in social networks. Despite its popularity in the data mining community, there is a lack of efficient distributed algorithms to solve the problem for big data sets. We propose a high-performance distributed-memory parallel algorithm that computes the factorization by iteratively solving alternating non-negative least squares (NLS) subproblems for $\WW$ and $\HH$. It maintains the data and factor matrices in memory (distributed across processors), uses MPI for interprocessor communication, and, in the dense case, provably minimizes communication costs (under mild assumptions). As opposed to previous implementation, our algorithm is also flexible: It performs well for both dense and sparse matrices, and allows the user to choose any one of the multiple algorithms for solving the updates to low rank factors $\WW$ and $\HH$ within the alternating iterations.

Kannan, Ramakrishnan↗