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At least 865 records · Page 48

Sequencing and analysis of 131 SARS-CoV-2 isolates in previously sampled and unsampled regions of Jordan from 2020 to 2023

The Hashemite Kingdom of Jordan remains an understudied country for next generation sequencing analysis of SARS-CoV-2 genomes collected during the 2019 pandemic. Here we provide 131 additional reference genomes collected between 2020–2023 from SARS-CoV-2-positive patients across Jordan. Phylogenetic analysis supports existing pandemic narratives of changing clade dominance over time and adds genomes in novel Jordanian locations and timepoints to make Jordan SARS-CoV-2 databases more comprehensive. Samples from the less-sequenced cities of Ajloun, Jaresh, Karak, and Madaba identified previously unreported lineages while Amman, Irbid, and Zarqa have existing sequencing efforts bolstered. Despite many incomplete patient records and a relatively small sample size, we observe interesting symptom patterns that support existing global and Jordanian pandemic narratives. We note how in-country COVID-19 pandemic genomic studies showcase Jordan’s efforts to expand next generation sequencing capabilities, especially through the leveraging of EDGE COVID-19, a bioinformatics platform for performing rapid, batched analysis of SARS-CoV-2 sequencing that streamlines sample processing prepared from a network of hospital locations.

60 APPLIED LIFE SCIENCES↗

Strengthening of enterococcal biofilms by Esp

Multidrug-resistant (MDR) Enterococcus faecalis are major causes of hospital-acquired infections. Numerous clinical strains of E . faecalis harbor a large pathogenicity island that encodes enterococcal surface protein (Esp), which is suggested to promote biofilm production and virulence, but this remains controversial. To resolve this issue, we characterized the Esp N-terminal region, the portion implicated in biofilm production. Small angle X-ray scattering indicated that the N-terminal region had a globular head, which consisted of two DEv-Ig domains as visualized by X-ray crystallography, followed by an extended tail. The N-terminal region was not required for biofilm production but instead significantly strengthened biofilms against mechanical or degradative disruption, greatly increasing retention of Enterococcus within biofilms. Biofilm strengthening required low pH, which resulted in Esp unfolding, aggregating, and forming amyloid-like structures. The pH threshold for biofilm strengthening depended on protein stability. A truncated fragment of the first DEv-Ig domain, plausibly generated by a host protease, was the least stable and sufficient to strengthen biofilms at pH ≤ 5.0, while the entire N-terminal region and intact Esp on the enterococcal surface was more stable and required a pH ≤ 4.3. These results suggested a virulence role of Esp in strengthening enterococcal biofilms in acidic abiotic or host environments.

59 BASIC BIOLOGICAL SCIENCES↗

Modeling the emergence of viral resistance for SARS-CoV-2 during treatment with an anti-spike monoclonal antibody

To mitigate the loss of lives during the COVID-19 pandemic, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease. Monoclonal antibodies used to treat SARS-CoV-2 target the spike protein of the virus and block its ability to enter and infect target cells. Monoclonal antibody therapy can thus accelerate the decline in viral load and lower hospitalization rates among high-risk patients with variants susceptible to mAb therapy. However, viral resistance has been observed, in some cases leading to a transient viral rebound that can be as large as 3–4 orders of magnitude. As mAbs represent a proven treatment choice for SARS-CoV-2 and other viral infections, evaluation of treatment-emergent mAb resistance can help uncover underlying pathobiology of SARS-CoV-2 infection and may also help in the development of the next generation of mAb therapies. Although resistance can be expected, the large rebounds observed are much more difficult to explain. We hypothesize replenishment of target cells is necessary to generate the high transient viral rebound. Thus, we formulated two models with different mechanisms for target cell replenishment (homeostatic proliferation and return from an innate immune response antiviral state) and fit them to data from persons with SARS-CoV-2 treated with a mAb. We showed that both models can explain the emergence of resistant virus associated with high transient viral rebounds. We found that variations in the target cell supply rate and adaptive immunity parameters have a strong impact on the magnitude or observability of the viral rebound associated with the emergence of resistant virus. Both variations in target cell supply rate and adaptive immunity parameters may explain why only some individuals develop observable transient resistant viral rebound. Our study highlights the conditions that can lead to resistance and subsequent viral rebound in mAb treatments during acute infection.

60 APPLIED LIFE SCIENCES↗

Population as a proxy for infrastructure in the determination of event response and recovery resource allocations

Research into modeling of the quantification and prioritization of resources used in the recovery of lifeline critical infrastructure following disruptive incidents, such as hurricanes and earthquakes, has shown several factors to be important. Among these are population density and infrastructure density, event effects on infrastructure, and existence of an emergency response plan. The social sciences literature has a long history of correlating the population density and infrastructure density at a national scale, at a country-to-country level, mainly focused on transportation networks. This effort examines whether these correlations can be repeated at smaller geographic scales, for a variety of infrastructure types, so as to be able to use population data as a proxy for infrastructure data where infrastructure data is either incomplete or insufficiently granular. Using the best data available, this effort shows that strong correlations between infrastructure density for multiple types of infrastructure (e.g. miles of roads, hospital beds, miles of electric power transmission lines, and number of petroleum terminals) and population density do exist at known geographic boundaries (e.g. counties, service area boundaries) with exceptions that are explainable within the social sciences literature. Furthermore, the correlations identified provide a useful basis for ongoing research into the larger resource utilization problem.

58 GEOSCIENCES↗

The application of halloysite tubule nanoclay in drug delivery

Introduction: Natural and biocompatible clay nanotubes are among the best inorganic materials for drug nanoformulations. These halloysite tubes with SiO 2 on the outermost surface have diameter of ca. 50 nm, length around 1 micrometer and may be loaded with drugs at 10-30 wt. %. Narrow tube openings allow for controllable sustained drug release for hours, days or even weeks. Areas covered: Physical-chemical properties of these nanotubes are described followed by examples of drug-loading capabilities, release characteristics, and control of duration of release through the end tube capping with polymers. Development of halloysite-polymer composites such as tissue scaffolds and bone cement/dentist resin formulations with enhanced mechanical properties and extension of the drug release to 2-3 weeks are described. Examples of the compression properties of halloysite in tablets and capsules are also shown. Expert opinion: Here, we expect that clay nanotubes will be used primarily for non-injectable drug formulations, such as topical and oral dosage forms, cosmetics, as well as for composite materials with enhanced therapeutic effects. These include tissue scaffolds, bone cement and dentist resins with sustained release of antimicrobial and cell growth-promoting medicines (including proteins and DNA) as well as other formulations such as compounds for antiseptic treatment of hospitals.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Predictive Radiation Oncology – A New NCI–DOE Scientific Space and Community

With a widely attended virtual kickoff event on January 29, 2021, the National Cancer Institute (NCI) and the Department of Energy (DOE) launched a series of 4 interactive, interdisciplinary workshops—and a final concluding “World Café” on March 29, 2021—focused on advancing computational approaches for predictive oncology in the clinical and research domains of radiation oncology. These events reflect 3,870 human hours of virtual engagement with representation from 8 DOE national laboratories and the Frederick National Laboratory for Cancer Research (FNL), 4 research institutes, 5 cancer centers, 17 medical schools and teaching hospitals, 5 companies, 5 federal agencies, 3 research centers, and 27 universities. Here we summarize the workshops by first describing the background for the workshops. Participants identified twelve key questions—and collaborative parallel ideas—as the focus of work going forward to advance the field. These were then used to define short-term and longer-term “Blue Sky” goals. In addition, the group determined key success factors for predictive oncology in the context of radiation oncology, if not the future of all of medicine. These are: cross-discipline collaboration, targeted talent development, development of mechanistic mathematical and computational models and tools, and access to high-quality multiscale data that bridges mechanisms to phenotype. The workshop participants reported feeling energized and highly motivated to pursue next steps together to address the unmet needs in radiation oncology specifically and in cancer research generally and that NCI and DOE project goals align at the convergence of radiation therapy and advanced computing.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Reported light in the sleep environment: enhancement of the sleep diary

Light is the primary synchronizing cue for the circadian timing system, capable of exerting robust physiological effects, even with very dim and/or brief photic exposure. Mammals, including humans, are particularly susceptible to light at night. As such, measures of light in the sleeping environment are critical for evaluating sleep health. Sleep diaries provide inexpensive measures of sleep, but do not typically include light information. Four questions probing visual perception of light in the bedtime and waking environments were added to the Consensus Sleep Diary for Morning administration. As part of a lighting intervention study, 18 hospital Labor and Delivery Department personnel completed the sleep diary for 1 week in each of two experimental conditions while wearing Actiwatch devices equipped with photosensors. Diary responses were evaluated against photosensor values from the beginning and end of each rest interval (n=194 rest intervals), as well as against sleep measures, utilizing linear mixed models. Responses to light questions were related to actual light measures at bedtime, controlling for shift type and experimental condition. In addition, subjective light information at bedtime and waking was related to both objective and subjective sleep parameters, with data generally indicating poorer sleep with light in the sleeping environment. Questions addressing perception of light in the sleeping environment may provide a crude yet affordable metric of relative photic intensity. Further, as responses relate to sleep outcomes, subjective light information may yield valuable insights regarding mechanisms and outcomes of clinical significance in sleep and circadian research.

59 BASIC BIOLOGICAL SCIENCES↗

Antibody-Based Diagnostics and Production for High Consequence Animal Pathogens II

New Horizons Diagnostic Corporation (NHD) develops, manufactures, and tests products for the detection of bacteria and toxins in human, environmental, surface, food, and water samples for government, municipal and corporate customers. It offers diverse medical products, such as products for testing cholera, gonorrhea, syphilis, and drug abuse screening products. The major product line for NHD is the development, marketing and sales of rapid antibody based diagnostic kits. Infectious diseases spread through food or water is a common, distressing, and sometimes life-threatening problem for millions of people in the United States and around the world. World Health Organization (WHO) studies have shown that in 1996, infectious and parasitic diseases accounted for 43% of the 40 million deaths in developing countries. The U.S. Centers for Disease Control and Prevention (CDC) estimates 76 million people suffer foodborne illnesses each year in the United States, accounting for 325,000 hospitalizations and more than 5,000 deaths.

Morris, James E↗

From Bombs to Breast Cancer Imaging: Los Alamos National Laboratory

In the United States, one in eight women will be affected by breast cancer. According to the American Cancer Society, breast cancer is the most commonly diagnosed - as well as the second most fatal - cancer in American women. It is estimated that there will be nearly 200,000 diagnoses of breast cancer this year; more than 40,000 of these will be fatal. Although advances in medical technologies have greatly increased the odds of surviving the disease, the increase in screenings has not resulted in a significant reduction in the breast cancer mortality rate. Moreover, recent studies have even suggested that an increase in these methods might, in itself, cause cancer. A new tool for early detection and diagnosis of breast cancer, supported by an award from the Breast Cancer Research Program (BCRP) of the Congressionally Directed Medical Research Programs of Department of Defense, could give women a new advantage in the fight against breast cancer. This LANL-led project will integrate ultrasound tomography (UST) with recent discoveries in the field of cell and tissue biomechanics to improve breast cancer detection and characterization. UST uses ultrasound waves instead of X-rays to identify and characterize breast tumors. This technology reveals small mechanical-property changes within the breast. These changes are often the earliest signs of breast cancer. Additionally, UST is effective for women with dense breast tissue, who have a higher risk of developing breast cancer. Because the technology does not use radiation, UST can also be used as frequently as needed for women with a high risk of developing breast cancer. In contrast, mammography, the only routine breast-cancer screening tool currently available, is not effective for women with dense breast tissue and may come with unwanted side-effects caused by ionizing radiation. UST has great potential to become an alternative breast-cancer screening tool because of UST's advantages and benefits over mammography. Currently, there is fierce debate surrounding the age at which breast cancer screening should begin, and once begun, how often it should occur. The American Cancer Society recommends yearly mammograms starting at age 40. On the other hand, the U.S. Preventive Services Task Force recommends against routine so early. Rather, the Task Force recommends biennial mammography screening for women aged 50 to 74 years. The ten-year discrepancy in the onset of screening results from recent data suggesting that the frequent use of X-ray radiation during screenings could potentially increase the likelihood of developing cancer. This danger is increased by the low sensitivity and accuracy of mammograms, which sometimes require multiple screenings to yield results. Furthermore, mammograms are often not only inaccurate, but average appalling misdiagnoses rates: about 80% false positives and 15% false negatives. These misdiagnoses lead to unwarranted biopsies at an estimated health care cost of $2 billion per year, while at the same time, resulting in excessive cases of undetected cancer. As such, the National Cancer Institute recommends more studies on the advantages of types and frequency of screenings, as well as alternative screening options. The UST technology developed at LANL could be an alternative option to greatly improve the specificity and sensitivity of breast cancer screening without using ionizing radiation. LANL is developing high-resolution ultrasound tomography algorithms and a clinical ultrasound tomography scanner to conduct patient studies at the UNM Hospital. During UST scanning, the patient lies face-down while her breast, immersed in a tank of warm water, is scanned by phased-transducer arrays. UST uses recorded ultrasound signals to reconstruct a high-resolution three-dimensional image of the breast, showing the spatial distribution of mechanical properties within the breast. Breast cancers are detected by higher values of mechanical properties compared to surrounding tissues. Thus, high-resolution breast images obtained using LANL's novel UST algorithms have the potential to detect breast cancer at its earliest stage. The goal of this Multi-Team Award project is two-fold: (1) develop a novel, safe and cost-effective breast-imaging technique, and (2) improve the specificity and sensitivity of breast cancer imaging. The project is expected to integrate basic research with clinical studies, perform substantive cross-disciplinary training among scientists on the teams and involve participation of consumer advocates. Those involved in the project are optimistic about future developments.

45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEF↗

Thermal Energy Corporation Combined Heat and Power Project

To meet the planned heating and cooling load growth at the Texas Medical Center (TMC), Thermal Energy Corporation (TECO) implemented Phase 1 of a Master Plan to install an additional 32,000 tons of chilled water capacity, a 75,000 ton-hour (8.8 million gallon) Thermal Energy Storage (TES) tank, and a 48 MW Combined Heat and Power (CHP) system. The Department of Energy selected TMC for a $10 million grant award as part of the Financial Assistance Funding Opportunity Announcement, U.S. Department of Energy National Energy Technology, Recovery Act: Deployment of Combined Heat and Power (CHP) Systems, District Energy Systems, Waste Energy Recovery Systems, and Efficiency Industrial Equipment Funding Opportunity Number: DE-FOA-0000044 to support the installation of a new 48 MW CHP system at the TMC located just outside downtown Houston. As the largest medical center in the world, TMC is home to many of the nation's best hospitals, physicians, researchers, educational institutions, and health care providers. TMC provides care to approximately six million patients each year, and medical instruction to over 71,000 students. A medical center the size of TMC has enormous electricity and thermal energy demands to help it carry out its mission. Reliable, high-quality steam and chilled water are of utmost importance to the operations of its many facilities. For example, advanced medical equipment, laboratories, laundry facilities, space heating and cooling all rely on the generation of heat and power. As result of this project TECO provides this mission critical heating and cooling to TMC utilizing a system that is both energy-efficient and reliable since it provides the capability to run on power independent of the already strained regional electric grid. This allows the medical center to focus on its primary mission providing top quality medical care and instruction without worrying about excessive energy costs or the loss of heating and cooling due to the risk of power outages. TECO's operation is the largest Chilled Water District Energy System in the United States. The company used DOE's funding to help install a new high efficiency CHP system consisting of a Combustion Turbine and a Heat Recovery Steam Generator. This CHP installation was just part of a larger project undertaken by TECO to ensure that it can continue to meet TMC's growing needs. The complete efficiency overhaul that TECO undertook supported more than 1,000 direct and indirect jobs in manufacturing, engineering, and construction, with approximately 400 of those being jobs directly associated with construction of the combined heat and power plant. This showcase industrial scale CHP project, serving a critical component of the nation's healthcare infrastructure, directly and immediately supported the energy efficiency and job creation goals established by ARRA and DOE. It also provided an unsurpassed model of a district energy CHP application that can be replicated within other energy intensive applications in the industrial, institutional and commercial sectors.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

An optimized hadrontherapy installation based on multiple-extraction, ultra-fast cycling FFAG

Propose an innovative concept of simultaneous beam delivery to several hadrontherapy treatment rooms, based on a technology of multiple-extraction fixed-field synchrotron accelerator, and on adapted hospital architecture. This concept will reduce treatment cost, bring it closer to conventional X-ray cost, making hadronthrapy accessible to greater number of patients.

43 PARTICLE ACCELERATORS↗

Community Wind Benefits (Fact Sheet)

While most wind power projects are owned by companies with limited local ties, community wind projects are owned by the local community. Community wind projects are defined by an ownership model instead of by the type or size of turbine. Community wind projects have multiple applications and can be used by schools, hospitals, businesses, farms, ranches, or community facilities to supply local electricity. Rural electric cooperatives or municipal utilities can own community wind projects and use them to diversify electricity supplies. Community wind projects can also consist of groups of local individuals who form independent power producer groups or limited liability corporations to sell the power the turbines produce to a local electricity supplier (Rynne et al. 2011).

17 WIND ENERGY↗

An optimized hadron therapy installation based on multiple-extraction, ultra-fast cycling FFAG

Propose an innovative concept of simultaneous beam delivery to several hadrontherapy treatment rooms, based on a technology of multiple-extraction fixed-field synchrotron accelerator, and on adapted hospital architecture. This concept will reduce treatment cost, bring it closer to conventional X-ray cost, making hadronthrapy accessible to greater number of patients.

43 PARTICLE ACCELERATORS↗

Environmental Assessment Lakeview Geothermal Project

The Town of Lakeview is proposing to construct and operate a geothermal direct use district heating system in Lakeview, Oregon. The proposed project would be in Lake County, Oregon, within the Lakeview Known Geothermal Resources Area (KGRA). The proposed project includes the following elements: Drilling, testing, and completion of a new production well and geothermal water injection well; construction and operation of a geothermal production fluid pipeline from the well pad to various Town buildings (i.e., local schools, hospital, and Lake County Industrial Park) and back to a geothermal water injection well. This EA describes the proposed project, the alternatives considered, and presents the environmental analysis pursuant to the National Environmental Policy Act. The project would not result in adverse effects to the environment with the implementation of environmental protection measures.

15 GEOTHERMAL ENERGY↗

Fuel Cell Power Model Version 2: Startup Guide, System Designs, and Case Studies. Modeling Electricity, Heat, and Hydrogen Generation from Fuel Cell-Based Distributed Energy Systems

This guide helps users get started with the U.S. Department of Energy/National Renewable Energy Laboratory Fuel Cell Power (FCPower) Model Version 2, which is a Microsoft Excel workbook that analyzes the technical and economic aspects of high-temperature fuel cell-based distributed energy systems with the aim of providing consistent, transparent, comparable results. This type of energy system would provide onsite-generated heat and electricity to large end users such as hospitals and office complexes. The hydrogen produced could be used for fueling vehicles or stored for later conversion to electricity.

08 HYDROGEN↗

A modeling framework for investment planning in interdependent infrastructures in multi-hazard environments.

Currently, much of protection planning is conducted separately for each infrastructure and hazard. Limited funding requires a balance of expenditures between terrorism and natural hazards based on potential impacts. This report documents the results of a Laboratory Directed Research & Development (LDRD) project that created a modeling framework for investment planning in interdependent infrastructures focused on multiple hazards, including terrorism. To develop this framework, three modeling elements were integrated: natural hazards, terrorism, and interdependent infrastructures. For natural hazards, a methodology was created for specifying events consistent with regional hazards. For terrorism, we modeled the terrorist s actions based on assumptions regarding their knowledge, goals, and target identification strategy. For infrastructures, we focused on predicting post-event performance due to specific terrorist attacks and natural hazard events, tempered by appropriate infrastructure investments. We demonstrate the utility of this framework with various examples, including protection of electric power, roadway, and hospital networks.

Brown, Nathanael J. K.↗

Long-term Energy and Emissions Savings Potential in New York City Buildings

The New York State Energy Research and Development Authority (NYSERDA) partnered with the Brookhaven National Laboratory (BNL) and the City University of New York (CUNY) to develop an integrated methodology that is capable of quantifying the impact of energy efficiency and load management options in buildings, including CUNY’s campus buildings, housing projects, hospitals, and hotels, while capturing the synergies and offsets in a complex and integrated energy-environmental system. The results of this work serve as a guideline in implementing urban energy efficiency and other forms of urban environmental improvement through cost-effective planning at the institutional and local level.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗