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The Los Angeles (LA) Metro Purple Line (D-Line) Extension project requires the design and construction of deep station excavations and tunnels for rail transit from downtown to west LA. The tunnel alignment for Reach 2 of the Westside Purple Line Extension 1 construction transects naturally-occurring tar-infused soils, which have been known to cause challenging construction conditions in southern California, as well as many other locations around the world. Two stations in similar geology but located within and outside tar soils were compared. The soil investigations of the tunnels and station excavations consisted of subsurface exploration including deep soil borings, Cone Penetration Testing (CPT), seismic velocity measurements, pressuremeter testing, and gas measurements, among others. The results of CPT and shear-wave velocity testing provide extensive data in tar soils unique to Southern California and an opportunity to increase our understanding of four-phase soil materials and the effects of tar on soil behavior interpretation and engineering properties. CPT correlations for conventional (non-tar-infused) soils were found to be inadequate for tar soils in the Los Angeles basin. The CPT based Soil Behavior Type Index (SBTn) determined in tar soils suggested the presence of much finer-grained material than determined from laboratory testing and field observations. Additionally, the presence of tar soils amplified the difference between CPT correlations for shear wave velocity (Vs) and direct Vs seismic CPT measurements. 

Estimating excavation-induced ground surface displacements in urban areas is needed to assess potential structure damage. Empirical settlement distribution models have been widely used to estimate the zone of influence and ground response behind braced excavation walls. Three underground station excavations, part of the Los Angeles Metro’s K Line Crenshaw/LAX Transit Project, offer a unique opportunity to collect field instrumentation data to improve estimates of ground deformations. One excavation employed cross-lot braces and soldier piles and wood lagging while the other two were supported by cross-lot braces and stiffer Cutter-Soil-Mixing (CSM) walls. For the excavations with stiff support systems and relatively small wall movements, upward surface displacement or heave governed the ground surface response, while surface settlement was measured at the excavation with the more flexible wall system. This heave behavior is often masked by settlement caused by relatively large wall movements, and is thus commonly disregarded. By idealizing the excavation unloading as an upward strip load at the ground surface, the Boussinesq solution for elastic upward movement can be used in combination with a settlement component resulting from lateral wall movements to estimate the magnitude and distribution of excavation-induced surface displacements. 

Empirical methods for estimating tunneling-induced ground movements have been widely adopted in the tunneling industry. The transverse surface settlement profile can be described by a Gaussian curve or a modified Gaussian curve whose maximum value and trough width are related to volume loss. Volume loss in turn is related to soil type, tunnel geometry, and construction techniques. Several empirical equations have been developed based on the Gaussian curve and the assumptions of (1) trough width dependency on tunnel depth and ground condition; and (2) volume loss dependency on the ground type and construction techniques. For Earth Pressure Balance Machine (EPBM) tunneling, a volume loss of 0.5% in granular soils and 1%–2% the soft clay has been assumed in the past as an initial estimate. However, with complete filling and pressurization of both the shield (overcut) gap and the grouted tail gap around the lining, volume losses below 0.1% to 0.2% are being achieved in the alluvial granular and clay soils on current Los Angeles Metro tunneling projects. The LA Metro K Line Crenshaw/LAX transit project, tunneled from 2016 to 2018, has provided an opportunity to acquire and organize data on compatible data management systems, and evaluate the extensive field monitoring data for ground conditions specific to predominately granular soils in Old Alluvium. These data allow for the improvement of current empirical methods and correlations for predicting surface settlement induced by EPBM tunnels. The approximately 1-mi (1.6-km)-long, 20.6-ft (6.5-m)-diameter twin tunnels were excavated by an EPBM in a dense sand layer overlain by a silt/clay layer. The cover-to-diameter ratio was consistently about 2. The settlements and volume losses are observed to be heavily dependent on the face/shield pressures. In general, maintaining continuous pressures can significantly reduce settlements. An equation for estimating the volume loss based on the measured EPBM shield pressures is proposed. This equation can be used with the existing empirical methods to estimate the surface settlement profile transverse to the longitudinal axis of the tunnel. 

Abstract Objective: The aim of this study was to investigate the performance of key hospital units associated with emergency care of both routine emergency and pandemic (COVID-19) patients under capacity enhancing strategies. Methods: This investigation was conducted using whole-hospital, resource-constrained, patient-based, stochastic, discrete-event, simulation models of a generic 200-bed urban U.S. tertiary hospital serving routine emergency and COVID-19 patients. Systematically designed numerical experiments were conducted to provide generalizable insights into how hospital functionality may be affected by the care of COVID-19 pandemic patients along specially designated care paths, under changing pandemic situations, from getting ready to turning all of its resources to pandemic care. Results: Several insights are presented. For example, each day of reduction in average ICU length of stay increases intensive care unit patient throughput by up to 24% for high COVID-19 daily patient arrival levels. The potential of 5 specific interventions and 2 critical shifts in care strategies to significantly increase hospital capacity is also described. Conclusions: These estimates enable hospitals to repurpose space, modify operations, implement crisis standards of care, collaborate with other health care facilities, or request external support, thereby increasing the likelihood that arriving patients will find an open staffed bed when 1 is needed. 

The efficacy of paclitaxel (PTX) is limited due to its poor solubility, poor bioavailability, and acquired drug resistance mechanisms. Designing paclitaxel prodrugs can improve its anticancer activity and enable formulation of nanoparticles. Overall, the aim of this work is to improve the potency of paclitaxel with prodrug synthesis, nanoparticle formation, and synergistic formulation with lapatinib. Specifically, we improve potency of paclitaxel by conjugating it to α-tocopherol (vitamin E) to produce a hydrophobic prodrug (Pro); this increase in potency is indicated by the 8-fold decrease in half maximal inhibitory concentration (IC50) concentration in ovarian cancer cell line, OVCA-432, used as a model system. The efficacy of the paclitaxel prodrug was further enhanced by encapsulation into pH-labile nanoparticles using Flash NanoPrecipitation (FNP), a rapid, polymer directed self-assembly method. There was an 1100-fold decrease in IC50 concentration upon formulating the prodrug into nanoparticles. Notably, the prodrug formulations were 5-fold more potent than paclitaxel nanoparticles. Finally, the cytotoxic effects were further enhanced by co-encapsulating the prodrug with lapatinib (LAP). Formulating the drug combination resulted in synergistic interactions as indicated by the combination index (CI) of 0.51. Overall, these results demonstrate this prodrug combined with nanoparticle formulation and combination therapy is a promising approach for enhancing paclitaxel potency. 

ABSTRACT The diversified NF-κB transcription factor family has been extensively characterized in organisms ranging from flies to humans. However, homologs of NF-κB and many upstream signaling components have recently been characterized in basal phyla, including Cnidaria (sea anemones, corals, hydras, and jellyfish), Porifera (sponges), and single-celled protists, including Capsaspora owczarzaki and some choanoflagellates. Herein, we review what is known about basal NF-κBs and how that knowledge informs on the evolution and conservation of key sequences and domains in NF-κB, as well as the regulation of NF-κB activity. The structures and DNA-binding activities of basal NF-κB proteins resemble those of mammalian NF-κB p100 proteins, and their posttranslational activation appears to have aspects of both canonical and noncanonical pathways in mammals. Several studies suggest that the single NF-κB proteins found in some basal organisms have dual roles in development and immunity. Further research on NF-κB in invertebrates will reveal information about the evolutionary roots of this major signaling pathway, will shed light on the origins of regulated innate immunity, and may have relevance to our understanding of the responses of ecologically important organisms to changing environmental conditions and emerging pathogen-based diseases. 

We prove that the knots [Formula: see text] and [Formula: see text] both have stick number 10. These are the first non-torus prime knots with more than 9 crossings for which the exact stick number is known. 

ABSTRACT We present a sample of 706, z < 1.5 active galactic nuclei (AGNs) selected from optical photometric variability in three of the Dark Energy Survey (DES) deep fields (E2, C3, and X3) over an area of 4.64 deg2. We construct light curves using difference imaging aperture photometry for resolved sources and non-difference imaging PSF photometry for unresolved sources, respectively, and characterize the variability significance. Our DES light curves have a mean cadence of 7 d, a 6-yr baseline, and a single-epoch imaging depth of up to g ∼ 24.5. Using spectral energy distribution (SED) fitting, we find 26 out of total 706 variable galaxies are consistent with dwarf galaxies with a reliable stellar mass estimate ($M_{\ast }\lt 10^{9.5}\, {\rm M}_\odot$; median photometric redshift of 0.9). We were able to constrain rapid characteristic variability time-scales (∼ weeks) using the DES light curves in 15 dwarf AGN candidates (a subset of our variable AGN candidates) at a median photometric redshift of 0.4. This rapid variability is consistent with their low black hole (BH) masses. We confirm the low-mass AGN nature of one source with a high S/N optical spectrum. We publish our catalogue, optical light curves, and supplementary data, such as X-ray properties and optical spectra, when available. We measure a variable AGN fraction versus stellar mass and compare to results from a forward model. This work demonstrates the feasibility of optical variability to identify AGNs with lower BH masses in deep fields, which may be more ‘pristine’ analogues of supermassive BH seeds.