The effects of local voids and imperfections of surrounding rock on the performance of existing tunnel lining

Local voids and imperfections may exist around the tunnel due to reasons such as inadequate back infill behind the lining, insufficient local lining thickness, ground water erosion, and other imperfect construction related activities. Such local voids and imperfections generally will lead to local contact loss and discontinuity in the ground-lining interaction. This paper evaluates the effect of local voids and imperfections developing around the tunnel vault area on the mechanical performance of tunnel lining. Based on field investigation results, a series of voids and imperfections with different geometries are defined to reflect cases resulting from different causes. Numerical parametric analyses were performed to investigate how those voids and imperfections influence the internal force and the safety factor of the lining, and the reinforced concrete lining were modelled with the smeared crack model to examine the development of cracking directions and patterns. Furthermore, the numerical approach was verified by comparing with field investigations and measurements. This study aims to investigate the most unsafe situation due to local voids and imperfections around the tunnel, and the modelled cracking feature shows a way to preliminary evaluate the possible local voids and imperfections behind tunnel lining based on field observation

A Redox-Based Autoinduction Strategy to Facilitate Expression of 5xCys-Tagged Proteins for Electrobiofabrication

Biofabrication utilizes biological materials and biological means, or mimics thereof, for assembly. When interfaced with microelectronics, electrobiofabricated assemblies enable exquisite sensing and reporting capabilities. We recently demonstrated that thiolated polyethylene glycol (PEG-SH) could be oxidatively assembled into a thin disulfide crosslinked hydrogel at an electrode surface; with sufficient oxidation, extra sulfenic acid groups are made available for covalent, disulfide coupling to sulfhydryl groups of proteins or peptides. We intentionally introduced a polycysteine tag (5xCys-tag) consisting of five consecutive cysteine residues at the C-terminus of a Streptococcal protein G to enable its covalent coupling to an electroassembled PEG-SH film. We found, however, that its expression and purification from E. coli was difficult, owing to the extra cysteine residues. We developed a redox-based autoinduction methodology that greatly enhanced the yield, especially in the soluble fraction of E. coli extracts. The redox component involved the deletion of oxyRS, a global regulator of the oxidative stress response and the autoinduction component integrated a quorum sensing (QS) switch that keys the secreted QS autoinducer-2 to induction. Interestingly, both methods helped when independently employed and further, when used in combination (i.e., autodinduced oxyRS mutant) the results were best—we found the highest total yield and highest yield in the soluble fraction. We hypothesize that the production host was less prone to severe metabolic perturbations that might reduce yield or drive sequestration of the -tagged protein into inclusion bodies. We expect this methodology will be useful for the expression of many such Cys-tagged proteins, ultimately enabling a diverse array of functionalized devices

Evaluation of 18 satellite- and model-based soil moisture products using in situ measurements from 826 sensors

Information about the spatiotemporal variability of soil moisture is critical for many purposes, including monitoring of hydrologic extremes, irrigation scheduling, and prediction of agricultural yields. We evaluated the temporal dynamics of 18 state-of-the-art (quasi-)global near-surface soil moisture products, including six based on satellite retrievals, six based on models without satellite data assimilation (referred to hereafter as "open-loop" models), and six based on models that assimilate satellite soil moisture or brightness temperature data. Seven of the products are introduced for the first time in this study: one multi-sensor merged satellite product called MeMo (Merged soil Moisture) and six estimates from the HBV (Hydrologiska Byrans Vattenbalansavdelning) model with three precipitation inputs (ERA5, IMERG, and MSWEP) with and without assimilation of SMAPL3E satellite retrievals, respectively. As reference, we used in situ soil moisture measurements between 2015 and 2019 at 5 cm depth from 826 sensors, located primarily in the USA and Europe. The 3-hourly Pearson correlation (R) was chosen as the primary performance metric. We found that application of the Soil Wetness Index (SWI) smoothing filter resulted in improved performance for all satellite products. The best-to-worst performance ranking of the four single-sensor satellite products was SMAPL3E(SWI), SMOSSWI, AMSR2(SWI), and ASCAT(SWI), with the L-band-based SMAPL3ESWI (median R of 0.72) outperforming the others at 50% of the sites. Among the two multi-sensor satellite products (MeMo and ESA-CCISWI), MeMo performed better on average (median R of 0.72 versus 0.67), probably due to the inclusion of SMAPL3ESWI. The best-to-worst performance ranking of the six openloop models was HBV-MSWEP, HBV-ERA5, ERA5-Land, HBV-IMERG, VIC-PGF, and GLDAS-Noah. This ranking largely reflects the quality of the precipitation forcing. HBV-MSWEP (median R of 0.78) performed best not just among the open-loop models but among all products. The calibration of HBV improved the median R by C0 :12 on average compared to random parameters, highlighting the importance of model calibration. The best-to-worst performance ranking of the six models with satellite data assimilation was HBV-MSWEP+SMAPL3E, HBV-ERA5+SMAPL3E, GLEAM, SMAPL4, HBV-IMERG+SMAPL3E, and ERA5. The assimilation of SMAPL3E retrievals into HBV-IMERG improved the median R by C0:06, suggesting that data assimilation yields significant benefits at the global scale

Regulation of pH by Carbonic Anhydrase 9 Mediates Survival of Pancreatic Cancer Cells With Activated KRAS in Response to Hypoxia.

Background & Aims Most pancreatic ductal adenocarcinomas (PDACs) express an activated form of KRAS, become hypoxic and dysplastic, and are refractory to chemo and radiation therapies. To survive in the hypoxic environment, PDAC cells upregulate enzymes and transporters involved in pH regulation, including the extracellular facing carbonic anhydrase 9 (CA9). We evaluated the effect of blocking CA9, in combination with administration of gemcitabine, in mouse models of pancreatic cancer. Methods We knocked down expression of KRAS in human (PK-8 and PK-1) PDAC cells with small hairpin RNAs. Human and mouse (KrasG12D/Pdx1-Cre/Tp53/RosaYFP) PDAC cells were incubated with inhibitors of MEK (trametinib) or extracellular signal-regulated kinase (ERK), and some cells were cultured under hypoxic conditions. We measured levels and stability of the hypoxia-inducible factor 1 subunit alpha (HIF1A), endothelial PAS domain 1 protein (EPAS1, also called HIF2A), CA9, solute carrier family 16 member 4 (SLC16A4, also called MCT4), and SLC2A1 (also called GLUT1) by immunoblot analyses. We analyzed intracellular pH (pHi) and extracellular metabolic flux. We knocked down expression of CA9 in PDAC cells, or inhibited CA9 with SLC-0111, incubated them with gemcitabine, and assessed pHi, metabolic flux, and cytotoxicity under normoxic and hypoxic conditions. Cells were also injected into either immune-compromised or immune-competent mice and growth of xenograft tumors was assessed. Tumor fragments derived from patients with PDAC were surgically ligated to the pancreas of mice and the growth of tumors was assessed. We performed tissue microarray analyses of 205 human PDAC samples to measure levels of CA9 and associated expression of genes that regulate hypoxia with outcomes of patients using the Cancer Genome Atlas database. Results Under hypoxic conditions, PDAC cells had increased levels of HIF1A and HIF2A, upregulated expression of CA9, and activated glycolysis. Knockdown of KRAS in PDAC cells, or incubation with trametinib, reduced the posttranscriptional stabilization of HIF1A and HIF2A, upregulation of CA9, pHi, and glycolysis in response to hypoxia. CA9 was expressed by 66% of PDAC samples analyzed; high expression of genes associated with metabolic adaptation to hypoxia, including CA9, correlated with significantly reduced survival times of patients. Knockdown or pharmacologic inhibition of CA9 in PDAC cells significantly reduced pHi in cells under hypoxic conditions, decreased gemcitabine-induced glycolysis, and increased their sensitivity to gemcitabine. PDAC cells with knockdown of CA9 formed smaller xenograft tumors in mice, and injection of gemcitabine inhibited tumor growth and significantly increased survival times of mice. In mice with xenograft tumors grown from human PDAC cells, oral administration of SLC-0111 and injection of gemcitabine increased intratumor acidosis and increased cell death. These tumors, and tumors grown from PDAC patient-derived tumor fragments, grew more slowly than xenograft tumors in mice given control agents, resulting in longer survival times. In KrasG12D/Pdx1-Cre/Tp53/RosaYFP genetically modified mice, oral administration of SLC-0111 and injection of gemcitabine reduced numbers of B cells in tumors. Conclusions In response to hypoxia, PDAC cells that express activated KRAS increase expression of CA9, via stabilization of HIF1A and HIF2A, to regulate pH and glycolysis. Disruption of this pathway slows growth of PDAC xenograft tumors in mice and might be developed for treatment of pancreatic cancer

Reverse Engineering To Characterize Redox Properties: Revealing Melanin's Redox Activity through Mediated Electrochemical Probing

Temocin, Zulfikar/0000-0001-7151-9772; Panzella, Lucia/0000-0002-2662-8205; Payne, Gregory/0000-0001-6638-9459WOS: 000444792800003Melanins are ubiquitous in nature, yet their functions remain poorly understood, because their structures and properties elude characterization by conventional methods. Since many of the proposed functions of melanins (e.g., antioxidant, pro-oxidant, and radical scavenging) involve an exchange of electrons, we developed an electrochemical reverse engineering methodology to probe the redox properties of melanin. This mediated electrochemical probing (MEP) method (i) characterizes insoluble melanin particles that are localized adjacent to an electrode within a permeable hydrogel film, (ii) employs diffusible mediators to shuttle electrons between the electrode and melanin sample, and (iii) imposes complex sequences of input voltages and analyzes output response characteristics (e.g., currents) to reveal redox properties. Here, we illustrate the versatility of MEP and review results demonstrating that melanins have reversible redox activities, can exchange electrons with various reductants and oxidants, and can quench radicals either by donating or accepting electrons. These results suggest possible biological functionalities for melanin and motivate the use of MEP for characterizing additional (i.e., synthesized) materials whose functions rely on redox properties. More broadly, MEP is revealing a richness to redox activities that has previously been inaccessible to investigation.United States National Science FoundationNational Science Foundation (NSF) [DMREF-1435957]; Department of Defense (Defense Threat Reduction Agency)United States Department of DefenseDefense Threat Reduction Agency [HDTRA1-13-1-0037, HDTRA1-15-1-0058]The authors gratefully acknowledge financial support from the United States National Science Foundation (No. DMREF-1435957) and the Department of Defense (Defense Threat Reduction Agency; Nos. HDTRA1-13-1-0037 and HDTRA1-15-1-0058)

Flexible, Wide-Area Storage for Distributed Systems with WheelFS

WheelFS is a wide-area distributed storage system intended to help multi-site applications share data and gain fault tolerance. WheelFS takes the form of a distributed file system with a familiar POSIX interface. Its design allows applications to adjust the tradeoff between prompt visibility of updates from other sites and the ability for sites to operate independently despite failures and long delays. WheelFS allows these adjustments via semantic cues, which provide application control over consistency, failure handling, and file and replica placement. WheelFS is implemented as a user-level file system and is deployed on PlanetLab and Emulab. Three applications (a distributed Web cache, an email service and large file distribution) demonstrate that WheelFS's file system interface simplifies construction of distributed applications by allowing reuse of existing software. These applications would perform poorly with the strict semantics implied by a traditional file system interface, but by providing cues to WheelFS they are able to achieve good performance. Measurements show that applications built on WheelFS deliver comparable performance to services such as CoralCDN and BitTorrent that use specialized wide-area storage systems.National Science Foundation (U.S.) (Grant No. CNS-0720644)Microsoft Research AsiaTsinghua University (Beijing, China

Satellite Flood Inundation Assessment and Forecast Using SMAP and Landsat

The capability and synergistic use of multisource satellite observations for flood monitoring and forecasts is crucial for improving disaster preparedness and mitigation. Here, surface fractional water cover (FW) retrievals derived from Soil Moisture Active Passive (SMAP) L-band (1.4 GHz) brightness temperatures were used for flood assessment over southeast Africa during the Cyclone Idai event. We then focused on five subcatchments of the Pungwe basin and developed a machine learning based approach with the support of Google Earth Engine for daily (24-h) forecasting of FW and 30-m inundation downscaling and mapping. The Classification and Regression Trees model was selected and trained using retrievals derived from SMAP and Landsat coupled with rainfall forecasts from the NOAA Global Forecast System. Independent validation showed that FW predictions over randomly selected dates are highly correlated (R = 0.87) with the Landsat observations. The forecast results captured the flood temporal dynamics from the Idai event; and the associated 30-m downscaling results showed inundation spatial patterns consistent with independent satellite synthetic aperture radar observations. The data-driven approach provides new capacity for flood monitoring and forecasts leveraging synergistic satellite observations and big data analysis, which is particularly valuable for data sparse regions. </p

High-brightness X-ray free-electron laser with an optical undulator by pulse shaping.

A normal-incident flattop laser with a tapered end is proposed as an optical undulator to achieve a high-gain and high-brightness X-ray free electron laser (FEL). The synchronic interaction of an electron bunch with the normal incident laser is realized by tilting the laser pulse front. The intensity of the flattop laser is kept constant during the interaction time of the electron bunch and the laser along the focal plane of a cylindrical lens. Optical shaping to generate the desired flattop pulse with a tapered end from an original Gaussian pulse distribution is designed and simulated. The flattop laser with a tapered end can enhance the X-ray FEL beyond the exponential growth saturation power by one order to reach 1 Gigawatt as compared to that without a tapered end. The peak brightness can reach 1030 photons/mm2/mrad2/s/0.1% bandwidth, more than 10 orders brighter than the conventional incoherent Thompson Scattering X-ray source

Reverse Engineering To Characterize Redox Properties: Revealing Melanin's Redox Activity through Mediated Electrochemical Probing

Melanins are ubiquitous in nature, yet their functions remain poorly understood, because their structures and properties elude characterization by conventional methods. Since many of the proposed functions of melanins (e.g., antioxidant, pro-oxidant, and radical scavenging) involve an exchange of electrons, we developed an electrochemical reverse engineering methodology to probe the redox properties of melanin. This mediated electrochemical probing (MEP) method (i) characterizes insoluble melanin particles that are localized adjacent to an electrode within a permeable hydrogel film, (ii) employs diffusible mediators to shuttle electrons between the electrode and melanin sample, and (iii) imposes complex sequences of input voltages and analyzes output response characteristics (e.g., currents) to reveal redox properties. Here, we illustrate the versatility of MEP and review results demonstrating that melanins have reversible redox activities, can exchange electrons with various reductants and oxidants, and can quench radicals either by donating or accepting electrons. These results suggest possible biological functionalities for melanin and motivate the use of MEP for characterizing additional (i.e., synthesized) materials whose functions rely on redox properties. More broadly, MEP is revealing a richness to redox activities that has previously been inaccessible to investigatio