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At least 73 records · Page 4

Effects of processing on the efficacy and metabolites of Cistanche tubulosa using ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry

Abstract Cistanche tubulosa (CT), a well‐known traditional Chinese medicine, has always been processed with rice wine for the treatment of kidney‐yang deficiency syndrome (KYDS) since time immemorial. To explore the effect of processing on the efficacy and metabolites of CT in vivo , a comprehensive method using ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry was established for the analysis of the altered endogenous metabolites in response to the intervention of the raw and processed CT in KYDS model and the metabolites of the absorbed compounds in rats after gastric perfusion. It was shown that CT could improve KYDS, and the effect of the processed product was more significant. A total of 47 differential metabolites were identified in urine. Pathway analysis proved that purine metabolism; alanine, aspartate, and glutamate metabolism; and citrate cycle were the main pathways. Furthermore, 53 prototypes and 48 metabolites have been detected in rats. This was the first systematic research focus on the metabolites of raw and processed CT in vivo , which could provide a scientific basis for explaining the increasing efficiency of the processed CT. Moreover, it provides a valuable strategy for analyzing the chemical components and metabolites of other TCM prescriptions.

Lei, Huibo↗

Efficacy of a Short-Term Captive Broodstock Program Compared with Hatchery-Origin Spring Chinook Salmon Derived from the Same Population

Abstract We examined the efficacy of a one-generation (five brood years: 1997–2001) captive broodstock program for spring Chinook Salmon Oncorhynchus tshawytscha by comparing survival rates of captive broodstock progeny (CBP; F2) with that of hatchery-origin fish (HOR) from a conservation hatchery supplementation program in which both groups were derived from the Tucannon River (Washington State) population for the 2000–2006 brood years. Survival rates compared were egg to fry, fry to smolt, egg to smolt, total (ages 3–5) and adult (ages 4+) smolt-to-adult-return (SAR) survival, and total (ages 3–5) and adult (ages 4+) progeny-to-parent (P:P) ratio. Total escapement and adult P:P ratios were also examined to determine if observed demographic benefits to the population continued after the captive broodstock program ended. The CBP group had lower within-hatchery survival than the HOR group, with significant differences in survival at the egg-to-fry and egg-to-smolt stages due to poor egg viability. Mean untransformed total and adult SARs for the CBP were half those of the HOR group; however, SARs did not differ significantly. The CBP also had significantly lower total and adult P:P ratios than the HOR group and were below replacement for six of the seven brood years. While the captive broodstock provided additional fish for release that would not have been available otherwise, overall the CBP performed poorly and below expectations compared with the HOR group, both within the hatchery and after release. The captive broodstock program provided a short-term demographic boost, most notable in the 2008–2010 return years, but the benefit did not carry over after the program ended.

59 BASIC BIOLOGICAL SCIENCES↗

Efficacy and Costs of Restoring Wetland Breeding Habitat for Imperiled Amphibians in the Southeastern U.S.

Herbaceous isolated wetlands in the North American Southeastern Coastal Plain are important breeding sites for many imperiled amphibians. However, most are degraded from alterations to historic fire disturbance and hydrologic regimes. Without fire, encroaching woody vegetation can transition wetlands to more terrestrial conditions and negatively impact amphibian breeding habitat, yet few studies have experimentally tested the efficacy, cost, or temporal requirement of current methods to restore herbaceous wetland vegetation. Here, we tested the interaction of manipulating wetland canopy and leaf litter/duff to promote herbaceous vegetation within one year (i.e., one breeding season) in degraded herbaceous wetlands in South Carolina. We assessed plant response via herbaceous cover, composition, and species similarity to the wetland seed bank and then related treatment performance to treatment cost. Removing trees combined with burning, disturbing, or removing duff significantly increased herbaceous cover and proportions of wetland plants and graminoids. Removing trees alone did not improve herbaceous cover compared to closed-canopy controls, and manipulating duff alone had limited positive effects on plant cover and composition. The most expensive yet effective treatment was Tree Removal-Duff Removal, while Tree Removal-Duff Disturbance was the most cost-effective. At a minimum, we recommend removing trees and burning to kickstart herbaceous recovery. Promisingly, comparisons of our data with previous seed bank studies from these same wetlands indicate there was limited seed bank attrition during 30 years of woody encroachment. Results from this study should aid practitioners in choosing wetland restoration techniques to better conserve at-risk species in the Southeastern Coastal Plain.

54 ENVIRONMENTAL SCIENCES↗

Efficacy of Gadolinium Gallium Garnet (GGG) as a High-Impedance Optical Window for Shock Wave Experiments

We conducted a series of plate impact experiments to examine the efficacy of < 111>-oriented gadolinium gallium garnet (GGG) single crystals as high-impedance optical window for Photonic Doppler velocimetry (PDV) under shock and double-shock loading. At ~ 123 GPa, shocked GGG remains fully transparent to 1550 nm light for at least 250 ns without any signal degradation. Above 135 GPa, PDV data measured through GGG exhibit a gradual loss of fringe contrast following shock entrance, which eventually leads to transparency loss. The duration for which shocked GGG remains transparent decreases with increasing pressure, and at ~ 148 GPa, it becomes opaque within ~ 20–30 ns. This limits the use of GGG as an interferometry window between ~ 110–140 GPa under single shock loading. Within this pressure range, the refractive index of GGG increases linearly with density: n = 1.552 + 0.054ρ. In contrast to single shock loading, where GGG becomes opaque rapidly above ~ 140 GPa, double-shocked GGG remains optically transparent for over 100 ns when it is first shocked to ~ 123 GPa and then reshocked to significantly higher pressures (215–233 GPa). Our findings raise the exciting possibility of GGG being used as a high-impedance optical window in multi-shock and shock-ramp loading experiments.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Self-cleaning and de-pollution efficacies of photocatalytic architectural membranes

Photocatalytic self-cleaning “cool” roofs and walls can maintain high albedos, saving building cooling energy, reducing peak power demand, and mitigating the urban heat island effect. Other environmental benefits result from their de-polluting properties. Specimens from two different photocatalytic architectural membranes and a non-photocatalytic control were exposed alongside vertically, facing west, for two years at three California sites, and retrieved quarterly for testing. Photocatalytic materials showed excellent self-cleaning performance, retaining albedos of 0.74 – 0.75. By contrast, the control material exhibited an albedo loss of up to 0.10, with appreciable soiling observed by scanning electron microscopy. De-pollution capacity was assessed by quantifying NO removal and NOx deposition rates at 60 °C. Furthermore, efficacy varied with exposure location, weather conditions, and the nature of the photocatalytic material. Seasonal effects were observed, with partial inhibition during the dry season and reactivation during the rainy season.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Efficacy of SCMs to mitigate ASR in systems with higher alkali contents assessed by pore solution method

This study demonstrates the efficacy of supplementary cementitious materials (SCMs) to mitigate alkali-silica reaction (ASR) even when used in conjunction with cement of higher alkali contents (up to 1% Na{sub 2}O{sub eq}). The expansion of concrete prisms was studied immersed in simulated pore solution in order to address the limitations of conventional ASR testing methods, accelerated mortar bar test (AMBT) and concrete prism test (CPT). Expansion results demonstrate that 25% fly ash and 50% slag are both sufficient to mitigate ASR even with cements with alkali content up to 1% Na{sub 2}O{sub eq} and that the pore solution method is a viable alternative ASR testing method. Massive amounts of ASR products (~20 μm thickness) were observed in concretes without SCMs consistent with high degree of expansion and extensive cracking. Small amounts of ASR products (≤5 μm thickness) were also observed in concrete with SCMs despite absence of significant expansion.

36 MATERIALS SCIENCE↗

A workflow to assess the efficacy of brine extraction for managing injection-induced seismicity potential using data from a CO 2 injection site near Decatur, Illinois

Injection of CO 2 for storage in a geologic formation increases pore pressure and alters in situ stresses. Depending on the orientation of any existing fault and fracture planes, such as critically stressed planes, this stress alteration will modify normal stresses acting on planes and could result in frictional sliding and release stored energy in the form of seismicity. Brine extraction (BE) is a technique that can be applied prior to, or during, CO 2 injection to reduce pore pressure for increasing storage capacity and, potentially, for reducing the likelihood of frictional sliding. Here a workflow is described to assess the efficacy of BE for mitigating frictional sliding (i.e., seismicity) during injection and entails: site characterization, stress calculations and failure assessment, static and dynamic modeling, and BE operational planning. Site characterization describes the stress field used to calculate the Coulomb Failure Function (CFF) that constrains allowable pore pressure changes and injection rates in the numerical simulation of CO 2 injection scenarios. The inclusion of BE in the workflow allows for determination of the potential need for pressure reduction, and evaluation of the effectiveness of this operation. Example application of the workflow using an injection field dataset near Decatur, IL, provides insight on fracture planes and stresses at the site, formation properties and the impact of variable CO 2 injection-rate targets on whether BE plans are required. The study workflow indicates that BE could enhance CO 2 injection rate by 39% and correspondingly reduce the potential for injection-induced seismicity as indicated by a reduction in CFF.

58 GEOSCIENCES↗

Comparison of Clinical Efficacy of Neoadjuvant Chemoradiation Therapy Between Lower and Higher Radiation Doses for Carcinoma of the Esophagus and Gastroesophageal Junction: A Systematic Review

Neoadjuvant concurrent chemoradiation therapy (nCRT) plus surgery has been a standard treatment for locoregionally advanced esophageal cancer and carcinoma of the gastroesophageal junction (EC/GEJ), but the optimal preoperative radiation dose is still unclear. We performed this systematic review to explore the treatment efficacy and toxicity of different radiation dose levels and find an optimal dose‐fractionation strategy in EC/GEJ patients receiving nCRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Prospective Clinical Investigation of the Efficacy of Combination Radiation Therapy With Immune Checkpoint Inhibition

Immune checkpoint inhibitors (ICIs) lead to durable responses in a subset of patients with cancer, but most patients do not respond to ICI, prompting interest in combining immunotherapy with other therapeutic regimens. Preclinical evidence supports the potential for therapeutic synergy between immunotherapy and radiation therapy through modulation of the tumor microenvironment and antitumor immune responses. Local therapy also has the potential to overcome localized sites of relative immune suppression and resistance. Prospective clinical trials have been initiated to test these hypotheses in the clinic as well as to investigate the toxicities and adverse events associated with combination immunotherapy and radiation therapy. In this review, we discuss the emerging results from prospective clinical trials of combination immunotherapy and radiation therapy, the safety and efficacy of their combination, concordance with preclinical and retrospective data, and some of the remaining open questions to be addressed by future clinical trials.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Targeted Alpha Particle Therapy Remodels the Tumor Microenvironment and Improves Efficacy of Immunotherapy

The tumor microenvironment (TME) can severely impair immunotherapy efficacy by repressing the immune system. In a multiple myeloma (MM) murine model, we investigated the impact of targeted alpha particle therapy (TAT) on the immune TME. TAT was combined with an adoptive cell transfer of CD8 T cells (ACT), and the mechanisms of action of this combination were assessed at the tumor site.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

CD47 blockade enhances therapeutic efficacy of cisplatin against lung carcinoma in a murine model

Cisplatin (CDDP) is the first generation of platinum-based drug and is widely used to treat many cancers due to its potency. The present study aims to explore the effects of CDDP on lung carcinoma and its relationship with macrophage phagocytosis. In in vitro study, murine and human lung cancer cell lines were applied and treated with CDDP, CD47 antibody (aCD47), or CDDP plus aCD47. In in vivo study, a tumor xenograft animal model was treated with CDDP, aCD47, or CDDP plus aCD47. Real-time PCR was applied to determine the mRNA expressions. Enzyme-linked immunosorbent assay (ELISA), Western blotting, and Immunofluorescent staining were applied to determine the protein expressions. Flow cytometry was applied to analyze cell apoptosis, phagocytosis, and specific cell populations. CDDP enhanced the expressions of CD47 in lung cancer cells. Interestingly, the blockage of CD47 enhanced the macrophages' phagocytic activity on the CDDP-treated tumor cells. The treatment of CDDP and aCD47 exhibited anti-tumor effects and prolonged the LLC tumor-bearing mice survival time. Mechanistic studies revealed that the treatment of CDDP and aCD47 regulated the phagocytic activity of macrophage, percentage of CD8{sup +} T cells, and cytokines (tumor growth factor (TGF)-β, interleukin (IL)12p70, and interferon (IFN)-γ) in the tumor-bearing model. CD47 blockade enhanced therapeutic efficacy of cisplatin against lung carcinoma in vivo and in vitro.

60 APPLIED LIFE SCIENCES↗

Crystal structure of active CDK4-cyclin D and mechanistic basis for abemaciclib efficacy

Despite the biological and therapeutic relevance of CDK4/6 for the treatment of HR+, HER2- advanced breast cancer, the detailed mode of action of CDK4/6 inhibitors is not completely understood. Of particular interest, phosphorylation of CDK4 at T172 (pT172) is critical for generating the active conformation, yet no such crystal structure has been reported to date. We describe here the x-ray structure of active CDK4-cyclin D3 bound to the CDK4/6 inhibitor abemaciclib and discuss the key aspects of the catalytically-competent complex. Furthermore, the effect of CDK4/6 inhibitors on CDK4 T172 phosphorylation has not been explored, despite its role as a potential biomarker of CDK4/6 inhibitor response. We show mechanistically that CDK4/6i stabilize primed (pT172) CDK4-cyclin D complex and selectively displace p21 in responsive tumor cells. Stabilization of active CDK4-cyclin D1 complex can lead to pathway reactivation following alternate dosing regimen. Consequently, sustained binding of abemaciclib to CDK4 leads to potent cell cycle inhibition in breast cancer cell lines and prevents rebound activation of downstream signaling. Overall, our study provides key insights demonstrating that prolonged treatment with CDK4/6 inhibitors and composition of the CDK4/6-cyclin D complex are both critical determinants of abemaciclib efficacy, with implications for this class of anticancer therapy.

60 APPLIED LIFE SCIENCES↗

Evaluating efficacy of indoor non-pharmaceutical interventions against COVID-19 outbreaks with a coupled spatial-SIR agent-based simulation framework

Contagious respiratory diseases, such as COVID-19, depend on sufficiently prolonged exposures for the successful transmission of the underlying pathogen. It is important that organizations evaluate the efficacy of non-pharmaceutical interventions aimed at mitigating viral transmission among their personnel. We have developed a operational risk assessment simulation framework that couples a spatial agent-based model of movement with an agent-based SIR model to assess the relative risks of different intervention strategies. By applying our model on MIT’s Stata center, we assess the impacts of three possible dimensions of intervention: one-way vs unrestricted movement, population size allowed onsite, and frequency of leaving designated work location for breaks. We find that there is no significant impact made by one-way movement restrictions over unrestricted movement. Instead, we find that reducing the frequency at which individuals leave their workstations combined with lowering the number of individuals admitted below the current recommendations lowers the likelihood of highly connected individuals within the contact networks that emerge, which in turn lowers the overall risk of infection. We discover three classes of possible interventions based on their epidemiological effects. By assuming a direct relationship between data on secondary attack rates and transmissibility in the agent-based SIR model, we compare relative infection risk of four respiratory illnesses, MERS, SARS, COVID-19, and Measles, within the simulated area, and recommend appropriate intervention guidelines.

60 APPLIED LIFE SCIENCES↗

Revealing low-temperature plasma efficacy through a dose-rate assessment by DNA damage detection combined with machine learning models

Low-temperature plasmas have quickly emerged as alternative and unconventional types of radiation that offer great promise for various clinical modalities. As with other types of radiation, the therapeutic efficacy and safety of low-temperature plasmas are ubiquitous concerns, and assessing their dose rates is crucial in clinical settings. Unfortunately, assessing the dose rates by standard dosimetric techniques has been challenging. To overcome this difficulty, we proposed a dose-rate assessment framework that combined the predictive modeling of plasma-induced damage in DNA by machine learning with existing radiation dose-DNA damage correlations. Our results indicated that low-temperature plasmas have a remarkably high dose rate that can be tuned by various process parameters. This attribute is beneficial for inducing radiobiological effects in a more controllable manner.

59 BASIC BIOLOGICAL SCIENCES↗

Evaluating the efficacy and equity of environmental stopgap measures

Contemporary environmental policy is rife with measures that do not fully resolve a problem, but instead are proposed to “buy time” for the development and future implementation of more durable solutions. In this perspective, we define such measures as “stopgap measures,” and examine examples from wildfire risk management, hydrochlorofluorocarbon regulation, and Colorado River water management. We introduce an analytical framework to assess stopgaps, and apply this framework to solar geoengineering, a controversial stopgap for climate action. Studying stopgaps as a novel category of policy and management measures can help us understand the why stopgaps emerge, and weigh the equity and efficacy of stopgaps against other policy proposals

54 ENVIRONMENTAL SCIENCES↗

Evaluating the impact of air terminal geometry on lightning intercept efficacy under a strong background electric field

A comparative analysis of the attachment efficacy of sharpened vs blunted air terminals under a strong background DC electric field, similar to conditions found in naturally occurring lightning events, is presented. Testing was conducted using an oil-free, 17-stage, 1.4 MV bipolar Marx generator with a biased discharge plane that emulated the conditions found prior to the lightning return stroke. The biased discharge plane allowed the introduction of a strong DC electric field and subsequent corona formation on a time scale much longer than the brief duration over which the downward leader propagates. Initial observations indicate that despite a higher background electric field at the sharpened terminals, leading to pre-discharge corona formation where none is seen on the blunt terminal, both the sharpened and blunted terminals exhibit similar attachment probabilities during discharge events, with some discharge events attaching to both terminals.

54 ENVIRONMENTAL SCIENCES↗