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At least 163 records · Page 9

Optimization of Picosecond Laser Parameters for Surface Treatment of Composites Using a Design of Experiments (DOE) Approach

Based on guidelines from the Federal Aviation Administration, research supported by the NASA Advanced Composites Project is investigating methods to improve process control for surface preparation and pre-bond surface characterization on aerospace composite structures. The overall goal is to identify high fidelity, rapid, and reproducible surface treatments and surface characterization methods to reduce the uncertainty associated with the bonding process. The desired outcome is a more reliable bonded airframe structure, and to reduce time to achieve certification. In this work, a design of experiments (DoE) approach was conducted to determine optimum laser ablation conditions using a pulsed laser source with a nominal pulse width of 10 picoseconds. The laser power, frequency, scan speed, and number of passes (1 or 2) were varied within the laser system operating boundaries. Aerospace structural carbon fiber reinforced composites (Torayca® 3900-2/T800H) were laser treated, then characterized for contamination, and finally bonded for mechanical testing. Pre-bond characterization included water contact angle (WCA) using a handheld device, ablation depth measurement using scanning electron microscopy (SEM), and silicone contamination measurement using laser induced breakdown spectroscopy (LIBS). In order to accommodate the large number of specimens in the DoE, a rapid-screening, double cantilever beam (DCB) test specimen configuration was devised based on modifications to ASTM D5528. Specimens were tested to assess the failure modes observed under the various laser surface treatment parameters. The models obtained from this DoE indicated that results were most sensitive to variation in the average laser power. Excellent bond performance was observed with nearly 100% cohesive failure for a wide range of laser parameters. Below about 200 mW, adhesive failure was observed because contamination was left on the surface. For laser powers greater than about 600 mW, large amounts of fiber were exposed, and the failure mode was predominately fiber tear.

Palmieri, Frank L.↗

MEDPRAT Treatment Clusters: Improving Representation of Mission Medical Risk

INTRODUCTION The Medical Extensible Dynamic Probabilistic Risk Assessment Tool (MEDPRAT) implements a computational model that aims to quantify spaceflight medical risk by utilizing probabilistic techniques to simulate critical event incidence and outcomes over thousands of simulated mission trials. The goal of MEDPRAT is to characterize mission medical risk and provide insight into medical resource utilization. In order to analyze the medical resource space, treatment must be mapped from each simulated condition, and resources consumed as a result of this treatment must be tracked throughout the course of the mission. A new MEDPRAT feature, ‘treatment clusters’, provide a more sophisticated method of defining the structure and interaction between resources, more closely mimicking the way treatment is carried out clinically. METHODS Treatment clusters expand on the two existing treatment groupings (combination and alternate) adding a new grouping: bundled treatment. Treatment clusters may be combined to any depth, giving users the ability to specify complex treatment trees whose behavior is governed by several user-specified parameters. This approach emphasizes reusability, as treatment clusters, once defined, can be used to create more complex treatment trees or applied to many conditions. By configuring parameters for contribution, efficacy, necessity, primacy, and equivalence, resource relationships and dependencies can be more accurately represented, thereby allowing users to build capabilities with desired treatment properties, for example an intravenous capability for conditions such as anaphylaxis, acute radiation syndrome, etc. MEDPRAT v1.0 remains backward compatible with existing treatment structures, giving users the ability to define new treatment clusters as evidence becomes available, without having to recode their existing treatment databases. In addition to facilitating the representation of more complex treatment options, by pairing treatment clusters with the internal optimization routine, the MEDPRAT set selector, medical resources can be identified as organized in bundles, where appropriate, so that optimized resource sets include groups of highly-dependent resources only when all resources of the group are together. For example, it would be wasteful to include ultrasound gel but not an ultrasound machine, since the gel provides no benefit as a treatment without the ultrasound machine. With treatment clusters, the user may require that both resources are available to provide any benefit as treatment, so that if one resource is optimized out of the set, the other resource will be optimized out as well. RESULTS AND CONCLUSIONS We will report on MEDPRAT treatment clusters used in a bundling study under the IMPACT project of the ExMC element. We will discuss an example of a complex treatment tree. Through the implementation of this feature MEDPRAT enables treatment to be defined and applied in a way that is more representative of the real world, providing more accurate insight into mission medical risk and the medical resource space.

Lawrence Leinweber↗

Effect of dehydroepiandrosterone administration before in vitro fertilization on the live birth rate in poor ovarian responders according to the Bologna criteria: A randomised controlled trial

Abstract Objective To evaluate the effect of dehydroepiandrosterone (DHEA) pre‐treatment before in vitro fertilization and embryo transfer (IVF‐ET) on the live birth rate in infertile women with poor ovarian response (POR) defined according to the Bologna criteria. Design A randomized, double‐blind, placebo‐controlled trial. Setting Nine reproductive medical centers in China. Population A total of 821 participants with POR defined according to the Bologna criteria were enrolled in the study between April 2016 and December 2018. Methods Eligible participants were randomly assigned to receive either DHEA ( n = 410) or placebo ( n = 411) treatments for 4–12 weeks prior to IVF‐ET, in a 1:1 ratio. Main outcome measures Live birth rate after the first embryo transfer. Results Thirty‐six (8.8%) of 410 women in the DHEA group and 37 (9.0%) of 411 women in the placebo group had a live birth, with no significant difference observed between groups (relative risk, 0.98, 95% CI, 0.63–1.51; p = 0.911). There were no significant differences in the number of retrieved oocytes, and the rates of clinical pregnancy, pregnancy loss, and cumulative live births between the two groups. Conclusions DHEA administration prior to IVF‐ET had no beneficial effect on the live birth rate relative to placebo in women with POR defined according to the Bologna criteria. Tweetable Abstract No benefit was found in poor ovarian responders who received DHEA administration prior to IVF.

Wang, Ze↗

Picosecond Pulsed Laser Ablation for the Surface Preparation of Epoxy Composites

As part of a technical challenge under the Advanced Composites Program, methods for improving pre-bond process control for aerospace composite surface treatments and inspections, in conjunction with Federal Aviation Administration guidelines, are under investigation. The overall goal is to demonstrate high fidelity, rapid and reproducible surface treatment and surface characterization methods to reduce uncertainty associated with the bonding process. The desired outcomes are reliable bonded airframe structure, and reduced timeline to certification. In this work, laser ablation was conducted using a q-switched Nd:YVO4 laser capable of nominal pulse durations of 8 picoseconds (ps). Aerospace structural carbon fiber reinforced composites with an epoxy resin matrix were laser treated, characterized, processed into bonded assemblies and mechanically tested. The characterization of ablated surfaces were conducted using scanning electron microscopy (SEM), water contact angle (WCA) goniometry, micro laser induced breakdown spectroscopy (uLIBS), and electron spin resonance (ESR). The bond performance was assessed using a double cantilever beam (DCB) test with an epoxy adhesive. The surface characteristics and bond performance obtained from picosecond ablated carbon fiber reinforced plastics (CFRPs) are presented herein.

Palmieri, Frank↗

Diagnostic, Prognostic, and Therapeutic Use of Radiopharmaceuticals in the Context of SARS-CoV-2

The coronavirus disease 2019 (COVID-19) outbreak has devastated the healthcare systems and economies of over 200 countries in just a few months. The etiological agent of COVID-19, SARS-CoV-2, is a highly contagious virus that can be transmitted by asymptomatic and symptomatic carriers alike. While in vitro testing techniques have allowed for population-wide screening, prognostic tools are required to assess the disease severity and therapeutic response, contributing to improve the patient clinical outcomes. Moreover, no specific antiviral against COVID-19 exists at the time of publication, severely limiting treatment against the infection. Hence, there is an urgent clinical need for innovative therapeutic strategies that may contribute to manage the COVID-19 outbreak and prevent future pandemics. In this work, we critically examine recent diagnostic, prognostic, and therapeutic advancements for COVID-19 in the field of radiopharmaceuticals. First, we summarize the gold standard techniques used to diagnose COVID-19, including in vitro assays and imaging techniques, and then discuss how radionuclide-based nuclear imaging provides complementary information for prognosis and treatment management of infected patients. Second, we introduce new emerging types of radiotherapies that employ radioimmunoconjugates, which have shown selective cytotoxic response in oncological studies, and critically analyze how these compounds could be used as therapeutic agents against SARS-CoV-2. Finally, this Perspective further discusses the emerging applications of radionuclides to study the behavior of pulmonary SARS-CoV-2 aerosol particles.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Current status and future outlook for patient‐derived cancer models from a rare cancer research perspective

Abstract Rare cancers are a group of approximately 200 malignancies with extremely low incidences and with a wide variety of genotypes and phenotypes. Collectively, they are more common than any single malignancy. However, given the small numbers of individuals diagnosed with rare cancers, it is difficult to design clinical trials with sufficient patient numbers. Therefore, few effective anticancer drugs have been developed, and evidence‐based medicine is not always feasible for rare cancers. Consequently, their clinical outcomes are generally poorer. Cancer research requires adequate models that faithfully recapitulate molecular features and reproduce treatment responses of the original tumors. Such models allow us to focus on more efficacious drugs in the clinical studies. For rare cancers, patient‐derived cancer models are particularly important because the enrollment of sufficient patients is rarely attainable within a reasonable period of time. However, extremely few models are available for rare cancers. For example, cell lines and xenografts are available for only a limited number of histological subtypes of sarcomas; therefore, most sarcoma research is performed without such models, and a lack of adequate cancer models causes a lag in therapeutic development. The establishment of novel rare cancer models will dramatically facilitate rare cancer research and treatment development in the near future. This review focuses on the status of patient‐derived rare cancer models and discusses their pivotal problems and possibilities, using sarcomas as a representative rare cancer type. Multi‐institutional collaboration will help address the scarcity of patient‐derived rare cancer models.

Kondo, Tadashi↗

Sequence-Defined Nanotubes Assembled from IR780-Conjugated Peptoids for Chemophototherapy of Malignant Glioma

Near-infrared (NIR) laser-induced phototherapy through NIR agents has demonstrated the great potential for cancer therapy. However, insufficient tumor killing due to the nonuniform heat or cytotoxic singlet oxygen ( 1 O 2 ) distribution over tumors from phototherapy results in tumor recurrence and inferior outcomes. To achieve high tumor killing efficacy, one of the solutions is to employ the combinational treatment of phototherapy with other modalities, especially with chemotherapeutic agents. In this paper, a simple and effective multimodal therapeutic system was designed via combining chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT) to achieve the polytherapy of malignant glioma which is one of the most aggressive tumors in the brain. IR-780 (IR780) dye-labeled tube-forming peptoids (PepIR) were synthesized and self-assembled into crystalline nanotubes (PepIR nanotubes). These PepIR nanotubes showed an excellent efficacy for PDT/PTT because the IR780 photosensitizers were effectively packed and separated from each other within crystalline nanotubes by tuning IR780 density; thus, a self-quenching of these IR780 molecules was significantly reduced. Moreover, the efficient DOX loading achieved due to the nanotube large surface area contributed to an efficient and synergistic chemotherapy against glioma cells. Given the unique properties of peptoids and peptoid nanotubes, we believe that the developed multimodal DOX-loaded PepIR nanotubes in this work offer great promises for future glioma therapy in clinic.

60 APPLIED LIFE SCIENCES↗

Treatment of cholinergic‐induced status epilepticus with polytherapy targeting GABA and glutamate receptors

Abstract Despite new antiseizure medications, the development of cholinergic‐induced refractory status epilepticus (RSE) continues to be a therapeutic challenge as pharmacoresistance to benzodiazepines and other antiseizure medications quickly develops. Studies conducted by Epilepsia . 2005;46:142 demonstrated that the initiation and maintenance of cholinergic‐induced RSE are associated with trafficking and inactivation of gamma‐aminobutyric acid A receptors (GABA A R) thought to contribute to the development of benzodiazepine pharmacoresistance. In addition, Dr. Wasterlain's laboratory reported that increased N‐methyl‐ d ‐aspartate receptors (NMDAR) and alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (AMPAR) contribute to enhanced glutamatergic excitation ( Neurobiol Dis . 2013;54:225; Epilepsia . 2013;54:78). Thus, Dr. Wasterlain postulated that targeting both maladaptive responses of reduced inhibition and increased excitation that is associated with cholinergic‐induced RSE should improve therapeutic outcome. We currently review studies in several animal models of cholinergic‐induced RSE that demonstrate that benzodiazepine monotherapy has reduced efficacy when treatment is delayed and that polytherapy with drugs that include a benzodiazepine (eg midazolam and diazepam) to counter loss of inhibition, concurrent with an NMDA antagonist (eg ketamine) to reduce excitation provide improved efficacy. Improved efficacy with polytherapy against cholinergic‐induced seizure is demonstrated by reduction in (1) seizure severity, (2) epileptogenesis, and (3) neurodegeneration compared with monotherapy. Animal models reviewed include pilocarpine‐induced seizure in rats, organophosphorus nerve agent (OPNA)‐induced seizure in rats, and OPNA‐induced seizure in two mouse models: (1) carboxylesterase knockout (Es1 −/− ) mice which, similarly to humans, lack plasma carboxylesterase and (2) human acetylcholinesterase knock‐in carboxylesterase knockout (KIKO) mice. We also review studies showing that supplementing midazolam and ketamine with a third antiseizure medication (valproate or phenobarbital) that targets a nonbenzodiazepine site rapidly terminates RSE and provides further protection against cholinergic‐induced SE. Finally, we review studies on the benefits of simultaneous compared with sequential drug treatments and the clinical implications that lead us to predict improved efficacy of early combination drug therapies. The data generated from seminal rodent studies of efficacious treatment of cholinergic‐induced RSE conducted under Dr. Wasterlain's guidance suggest that future clinical trials should treat the inadequate inhibition and temper the excess excitation that characterize RSE and that early combination therapies may provide improved outcome over benzodiazepine monotherapy.

59 BASIC BIOLOGICAL SCIENCES↗

Influence of pre-existing defects on thermal transport in nuclear graphite

Nuclear graphite is a critical material in high-temperature nuclear reactors due to its superior thermal and mechanical properties. The manufacturing process leaves multi-scale ‘pre-existing’ defects that can affect thermal transport characteristics. Because these defects are remnant of graphitization temperature, they cannot be thermally annealed. This study employs a non-thermal electron wind force (EWF) annealing technique to avoid this obstacle. 2 min of EWF treatment of the as-received graphite IG-110 at temperatures below 100 °C led up to 67% increase in thermal diffusivity and ~ 35% decrease in electrical resistivity in average. Differential scanning calorimetry also showed similar outcome for specific heat. X-ray diffraction characterization was performed by fitting a bi-modal crystallite size distribution model to reveal the enhancement in crystallinity after the EWF treatment. The findings emphasize the potential of EWF annealing for optimizing thermal performance in nuclear graphite and its implications for reactor efficiency and safety.

Annealing↗

Cost-Effectiveness Analysis of Stereotactic Ablative Radiation Therapy in Patients With Oligometastatic Cancer

The Stereotactic Ablative Radiation therapy for Comprehensive Treatment of Oligometastatic Tumors phase 2 randomized clinical trial found that stereotactic ablative radiation therapy (SABR) improved outcomes among cancer patients with oligometastatic disease. Yet, the cost of SABR along with the large number of patients with oligometastatic disease raises the important question of value. This study sought to evaluate the cost-effectiveness of the addition of SABR compared with standard therapy alone among cancer patients with oligometastatic disease.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Gas hydrate deposit formation in transient flowloop tests and mitigation with a surface treatment

Thermodynamic and thermal mitigation strategies are traditionally utilized to prevent gas hydrate formation but may be rendered ineffective for certain unplanned, extended shut-in scenarios. Unfortunately, the current knowledge regarding transient gas hydrate formation has been extremely limited to only a few studies and unable to address this complex issue adequately. This work, conducted in a lab-scale flowloop, aims to add to the understanding of this area by delving into the implications of transient conditions on gas hydrate formation mechanisms, while also exploring a possible mitigation strategy of a surface treatment. Specifically, the effects of phase separation on gas hydrate formation locations, transportability, and plugging are presented for an oil-dominated system. An omniphobic surface treatment is shown to affect initial gas hydrate deposition and its wall adherence strength, as well as the overall plugging outcome. Overall, this work combines observational information with process data measurements to provide a better understanding of phase separated gas hydrate systems and passive deposition mitigation strategies. This can further aid advanced gas hydrate modeling efforts, which currently do not adequately address transient flow effects on phase separation/dispersion. Here, it offers representative gas hydrate testing for coatings, which have exclusively been limited to non-flowing and/or bench-scale analysis, to give confidence in their potential application as advanced deposition prevention tools.

03 NATURAL GAS↗

Oridonin interrupts cellular bioenergetics to suppress glioma cell growth by down‐regulating PCK2

We aim to evaluate the tumor metabolic suppressive activity of Oridonin (extract of Rabdosia rubescens ) in glioma and elucidate its potential mechanism. Effects of Oridonin on U251/U87 cells were determined by CCK8, RTCA, colony formation, flow cytometry, wound healing, and Transwell assay. Xenograft tumor model to evaluate the effect of Oridonin on glioma cells in vivo. Cellular bioenergetics were measured by Seahorse. RNA‐seq was performed to screen potential biological pathways in Oridonin treated cells. Bioinformatics analysis of PCK2 in glioma was performed based on TCGA/CGGA. Endogenous PCK2 was knocked‐down by lentivirus packaged shRNA. We found Oridonin significantly inhibited cell growth in U251/U87 in vitro and in vivo. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were decreased in Oridonin‐treated U251/U87 cells. Oridonin treatment led to PCK2 down‐regulation. Additionally, PCK2 was up‐regulated in higher grade glioma and correlated with poor outcomes. Furthermore, PCK2 depletion significantly inhibited cell growth and decreased OCR/ECAR in U251/U87 which coincided with the effects of Oridonin. Therefore, we evaluated the potent anti‐tumor property of Oridonin in glioma. Importantly, we demonstrated that PCK2 might be a novel target of Oridonin on glioma by inducing energy crisis and increasing oxidative stress.

Lin, Jianhu↗

Hybrid Particle Method for Computational Shock Physics

A long-standing area of research for Eulerian shock wave physics codes has been the treatment of strength and damage for materials. Here we present a method that will aid in the analysis of strength and failure in shock physics applications where excessive diffusion of critical variables can occur and control the solution outcome. Eulerian methods excel for large deformation simulations in general but are inaccurate in capturing structural behavior. Lagrangian methods provide better structural response, but finite element meshes can become tangled. Therefore, a technique for merging Lagrangian and Eulerian treatments of material response, within a single numerical framework, was implemented in the Multiple Component computational shock physics hydrocode. The capability is a Lagrangian/Eulerian Particle Method (LEPM) that uses particles to interface a Lagrangian treatment of material strength with a more traditional Eulerian treatment of the Equation of State (EOS). Lagrangian numerical methods avoid the advection diffusion found in Eulerian methods, which typically strongly affects strength constitutive law internal variables, such as equivalent plastic strain, porosity and/or damage. The Lagrangian capability enhances existing capabilities and permits accurate predictions of high rate, large deformation and/or shock of mechanical structures.

97 MATHEMATICS AND COMPUTING↗

Treatment of WHO Grade 2 Meningiomas With Stereotactic Radiosurgery: Identification of an Optimal Group for SRS Using RPA

This study assesses a large multi-institutional database to present the outcomes of World Health Organization grade 2 meningiomas treated with stereotactic radiosurgery (SRS). We also compare the 3-year progression-free survival (PFS) to that reported in the Radiation Therapy Oncology Group 0539 phase 2 cooperative group meningioma trial.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Inhibition of polyamine biosynthesis preserves β cell function in type 1 diabetes

In preclinical models, α-difluoromethylornithine (DFMO), an ornithine decarboxylase (ODC) inhibitor, delays the onset of type 1 diabetes (T1D) by reducing β cell stress. However, the mechanism of DFMO action and its human tolerability remain unclear. In this study, we show that mice with β cell ODC deletion are protected against toxin-induced diabetes, suggesting a cell-autonomous role of ODC during β cell stress. In a randomized controlled trial (ClinicalTrials.gov: NCT02384889) involving 41 recent-onset T1D subjects (3:1 drug:placebo) over a 3-month treatment period with a 3-month follow-up, DFMO (125–1,000 mg/m 2 ) is shown to meet its primary outcome of safety and tolerability. DFMO dose-dependently reduces urinary putrescine levels and, at higher doses, preserves C-peptide area under the curve without apparent immunomodulation. Transcriptomics and proteomics of DFMO-treated human islets exposed to cytokine stress reveal alterations in mRNA translation, nascent protein transport, and protein secretion. These findings suggest that DFMO may preserve β cell function in T1D through islet cell-autonomous effects.

60 APPLIED LIFE SCIENCES↗

Executive Summary of the American Radium Society Appropriate Use Criteria for Operable Esophageal and Gastroesophageal Junction Adenocarcinoma: Systematic Review and Guidelines

Limited guidance exists regarding the relative effectiveness of treatment options for nonmetastatic, operable patients with adenocarcinoma of the esophagus or gastroesophageal junction (GEJ). In this systematic review, the American Radium Society (ARS) gastrointestinal expert panel convened to develop Appropriate Use Criteria (AUC) evaluating how neoadjuvant and/or adjuvant treatment regimens compared with each other, surgery alone, or definitive chemoradiation in terms of response to therapy, quality of life, and oncologic outcomes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Regional Feedstock Partnership Biomass Quality Assessment Final Report

The United States (U.S.) Department of Energy (DOE) developed the Billion-Ton Vision to enable production of one-billion tons of sustainable, reliable biomass for the bioenergy industry by 2030 (Perlack et al., 2005). The Sun Grant Regional Feedstock Partnership (RFP) was organized to fill information gaps and validate biomass yield assumptions related to the Billion-Ton Study (Owens, 2018; Owens, Karlen, and Lacey, 2016). Along with the more than 130 scientific publications generated from these studies, yield and sustainability data from the RFP field trials not only validated the Billion-Ton estimates, but were critical in developing both the U.S. Billion-Ton Update report in 2011 and the 2016 Billion-Ton Report (DOE, 2011; 2016). The intention of this biomass quality assessment report is to build on these initial successes from the RFP field trials by focusing on variability in biomass quality data necessary to evaluate conversion performance. This report contains a summary of chemical quality results from samples collected as part of the RFP field trials. This report focuses on assessment of the impact of experimental agronomic designs on biomass properties followed by analyses of the impact of environmental and production variables on biomass properties. Datasets include species and other genetic variables, fertilizer treatments, harvest information, and yield, as well as other publicly available data such as precipitation, temperature, soil properties, and drought. The key outcomes from this chemical quality focused assessment have included: • Complete evaluation of the impacts of agronomic designs, genetics, and environmental conditions on chemical properties for Miscanthus, switchgrass, sorghum, energycane, mixed perennial grasses, and shrub willow short-rotation feedstocks • Over 30 peer review publications and technical reports focused on variability in quality data • Development of spatial and temporal environmental quality prediction maps for Miscanthus and switchgrass feedstocks allowing for comprehensive evaluation of variability in feedstock chemical quality across U.S. regions and over multiple harvest years

09 BIOMASS FUELS↗

Development, refinement, and testing of a short term solar flare prediction algorithm

Progress toward performance of the tasks and accomplishing the goals set forth in the two year Research Grant included primarily analysis of digital data sets and determination of methodology associated with the analysis of the very large, unique, and complex collection of digital solar magnetic field data. The treatment of each magnetogram as a unique set of data requiring special treatment was found to be necessary. It is determined that a person familiar with the data, the analysis system, and logical, coherent outcome of the analysis must conduct each analysis, and interact with the analysis program(s) significantly sometimes many iterations for successful calibration and analysis of the data set. With this interaction, the data sets yield valuable, coherent analyses. During this period, it was also decided that only data sets taken inside heliographic longitudes (Central Meridian Distance) East and West 30 degrees (within 30 degrees of the Central Meridian of the Sun). If the total data set is then found to be numerically inadequate for the final analysis, 30 - 45 degrees Central Meridian Distance data will then be analyzed. The Optical Data storage system (MSFC observatory) was found appropriate for use both in intermediate storage of the data (preliminary to analysis), and for storage of the analyzed data sets for later parametric extraction.

Smith, Jesse B., Jr.↗