Search

Chimeric antigen receptor (CAR)-engineered adoptive cell therapy marks a revolution in cancer treatment based on the highly successful responses to CAR T cell therapy in the treatment of blood cancers. Due to the versatile structure of CARs, this technology can be easily adapted to other immune cell types, including macrophages and NKs, and applied in the treatment of many other cancers. However, high costs and fatal adverse effects represent significant concerns for future development. In vitro transcribed (IVT) mRNA therapeutics, which possess a high safety profile and straightforward production methods, could provide a useful alternative for CAR cell construction. However, the low stability and transfection efficiency of IVT-mRNA in immune cells limit further applications. In this work, we successfully engineered CAR macrophages (CAR-Ms) and CAR T cells with CAR mRNA using lipid nanoparticles (LNPs). Both the LNP formulations and mRNA modifications were optimized for in vitro mRNA transfection. More importantly, the CAR macrophages and CAR T cells both demonstrated significant cytotoxic effects on B lymphoma in vitro, underscoring the great potential of mRNA-engineered adoptive cell therapy.

This article documents the earthquake ground motion database developed for the NGA-East Project, initiated as part of the Next Generation Attenuation (NGA) research program and led by the Pacific Earthquake Engineering Research Center (PEER). The project was focused on developing a ground motion characterization model (GMC) model for horizontal ground motions for the large region referred to as Central and Eastern North America (CENA). The CENA region covers most of the U.S. and Canada, from the Rocky Mountains to the Atlantic Ocean and is characterized tectonically as a stable continental region (SCR). The ground-motion database includes the two- and three-component ground-motion recordings from numerous selected events relevant to CENA (M> 2.5, with distances up to 3500 km) that have been recorded since 1976. The final database contains over 27,000 time series from 82 earthquakes and 1271 recording stations. The ground motion database includes uniformly processed time series, 5% damped pseudo-spectral acceleration (PSA) median-component ordinates for 429 periods ranging from 0.01 to 10 s, duration and Arias intensity in 5% increments, and Fourier amplitude spectra for different time windows. Ground motions and metadata for source, path, and site conditions were subjected to quality checks by topical working groups and the ground-motion model (GMM) developers. The NGA-East database constitutes the largest database of processed recorded ground motions in SRCs and is publicly available from the PEER ground-motion database website.

This article evaluates linear simulation-based and empirical site amplification models including site natural period dependency parameters to account for the distinctive amplification behavior near site fundamental frequencies resulting from the sharp impedance contrast between soil and underlying hard bedrock in central and eastern North America (CENA). The simulation-based amplification models are developed using 581,685 frequency-domain linear analyses generated from a parametric study and include VS30-scaling and site natural period (Tnat) parameters. The empirical models are derived from residuals analyses of ground-motion models for two reference conditions: B/C boundary (VS30= 760 m/s) and CENA hard-rock condition (VS= 3000 m/s). The simulation-based and empirical models are compared for 8 site profiles in CENA to measured horizontal-to-vertical (H/V) component response spectral (RS) ratios, the mean of linear simulations for similar sites, and one-dimensional (1D) linear site response analysis for four of these sites. Comparisons between observed and estimated site amplification behaviors highlight model dependency on Tnatin CENA. Model consistencies and differences related to the distinct linear amplification features near site fundamental frequency are discussed.

This article presents recommendations for nonlinear site amplification models in Central and Eastern North America (CENA), which are developed from one-dimensional site response analyses results and accompanies linear site amplification model in a companion article. Two median nonlinear amplification models using identical functional forms are produced as a function of VS30and peak ground acceleration for reference conditions (PGAr) of VS= 3000 m/s and VS30= 760 m/s. An epistemic uncertainty model on median nonlinear amplification is proposed as a piecewise functional form to generate reasonable variations of nonlinear amplification across the period and VS30ranges of interest. Limitations of the models are based on both the methodology of the model derivation and assumptions of nonlinear amplification model forms.

Site amplification models for Central and Eastern North America are developed from simulation results presented in a companion paper. Linear and nonlinear amplification functions are developed for response spectral (RS) accelerations and smoothed Fourier amplitude spectra (FAS). Linear RS model components include ground motion scaling with 30 m time-averaged shear wave velocity (VS30scaling) and the effects of site period and sediment depth. These models are modular and can be used with or without period or depth terms. Including these terms, especially site period, is desirable and improves model estimation. Modularity also allows linear and nonlinear amplification terms to be developed and combined with linear amplification models without bias. Nonlinear RS models reduce linear amplification as VS30decreases and the intensity of rock outcrop motions increases. Linear FAS models are tabulated amplification values as functions of VS30and depth; nonlinear FAS models are analogous to those for the RS. A linear model for correcting a VS30= 760 m/s rock condition to VS= 3,000 m/s is produced.

This paper presents the development of large-scale simulation-based data sets used to inform new site amplification models for Central and Eastern North America (CENA). Linear elastic, equivalent linear, and nonlinear one-dimensional site response simulations of site conditions in CENA are employed. An analysis tree is introduced to capture the range of expected CENA geologic conditions. Independent variables include the following: (1) representative and random shear wave velocity (VS) profiles using data from the literature; (2) randomized, nonlinear shear modulus reduction and damping vs. shear strain curves with constraint on soil shear strength; and (3) outcrop ground motions representative of the VS= 3,000 m/s CENA reference rock condition. The resulting database of 1,747,278 simulations is conditioned on several parameters relevant to site amplification, which facilitates model development that is the subject of a companion paper. The database is openly available for use by other researchers.

This study investigates the conditions for which one-dimensional (1-D) nonlinear (NL) site response analysis results are distinct from equivalent-linear (EL) results and provides guidance for predicting when differences are large enough to be of practical significance. Relative differences in spectral accelerations and Fourier amplitudes computed from NL and EL analyses are assessed for a range of site conditions and for suites of input motions appropriate for active crustal and stable continental regions. Among several considered parameters, EL/NL differences are most clearly dependent on shear strain index (Iγ), defined as the ratio of input motion peak velocity to time-averaged shear-wave velocity in the top 30 m of the soil profile. For small Iγ(generally under 0.03%), EL and NL results are practically identical, whereas at larger strains, differences can be significant for frequencies >0.3 Hz. Frequency-dependent Iγvalues are recommended for conditions above which NL analyses are preferred to EL.

The superior radiation dose distributions achievable with inverse-planned intensity-modulated radiation therapy (IMRT), allowing for unparalleled sparing of normal tissues and the potential for dose escalation, have resulted in its incredible popularity and demand. Inverse planning demands a keen understanding of radiographic anatomy for both tumor and critical structure definitions when making decisions regarding dose prescription and constraints for organs at risk. The most extensive investigational experience with this process has been in the treatment of prostate, head and neck, and gynecologic cancers. This review presents a consolidated collection and comparison of the techniques used in some of the most detailed studies involving IMRT for these commonly treated cancers.

This article contains results from a literary analysis of fifty scientific papers selected from the top 100 most-cited papers appearing in the Science Citation Indexfor the period 1945–1988. Most papers are from the field of biochemistry and became citation superstars because their authors discovered a method or material that numerous others could use in their own research. The typical paper has two authors, two tables, six figures, and twenty-two references. It adheres to the conventional topical organization, with the topics distributed as follows: 2 percent abstract, 5 percent introduction, 25 percent methods and materials, 50 percent results, 10 percent discussion, 4 percent conclusion, and 4 percent reference list. Tables and figures occupy about 30 percent of the article. With respect to the writing style, the average sentence is somewhat long (24 words) but not unreasonably so, and the sentence structure is simple greater than half the time. Moreover, sentences tend to rely heavily on to beverbs (about 80% of sentences have at least one) and abstract nouns (0.66 per sentence). Explanations for the typical form and writing style in these papers are provided.

In contrast to the literary artist we expect the scientist-writer to transmit information to the intended audience as accurately and clearly as possible. Nevertheless, a few scientists have managed to slip into their prose such rhetorical devices as anagram, acrostic, pun, metaphor, litotes, and neologism.

Technical periodicals and proceedings have been important instruments for transmitting news about scientific and technological discoveries for more than 300 years. The first such publications appeared amidst the birth of modem science when, for the first time, emphasis was placed on experiment as the basis for advancement of knowledge. Discussed in this article are the origin of the technical periodical and proceedings and their characteristics up to the end of the 18th century and the analysis of the writing style in an important technical paper written by Isaac Newton and published in 1672.

This article discusses the typical form and content of forty theoretical scientific papers. These papers were chosen from the 400 most-cited papers in the Science Citation Indexfor the period 1945–1988 (reported by Eugene Garfield in a series of recent essays appearing in Current Contents). It was found that the typical form for these papers is similar to that for experimental and methods papers, but the content differs substantially. In brief, the content follows the logical sequence: problem or need, assumptions made in attempting to solve problem or meet need, theorem derived from those assumptions and additional considerations, proof of theorem by logical reasoning or validation by comparison with what is established or establishable, conclusions from previous discussion, and recommendations on future experimental or theoretical work. Also, compared with experimental and methods papers, these theoretical papers have somewhat fewer figures and tables, but many more references and equations.