Shear-Wave Velocity Characterization of the USGS Hawaiian Strong-Motion Network on the Island of Hawaii and Development of an NEHRP Site-Class Map

To assess the level and nature of ground shaking in Hawaii for the purposes of earthquake hazard mitigation and seismic design, empirical ground-motion prediction models are desired. To develop such empirical relationships, knowledge of the subsurface site conditions beneath strong-motion stations is critical. Thus, as a first step to develop ground-motion prediction models for Hawaii, wspectral-analysis-of-surface-waves (SASW) profiling was performed at the 22 free-field U.S. Geological Survey (USGS) strong-motion sites on the Big Island to obtain shear-wave velocity (V(S)) data. Nineteen of these stations recorded the 2006 Kiholo Bay moment magnitude (M) 6.7 earthquake, and 17 stations recorded the triggered M 6.0 Mahukona earthquake. V(S) profiling was performed to reach depths of more than 100 ft. Most of the USGS stations are situated on sites underlain by basalt, based on surficial geologic maps. However, the sites have varying degrees of weathering and soil development. The remaining strong-motion stations are located on alluvium or volcanic ash. V(S30) (average V(S) in the top 30 m) values for the stations on basalt ranged from 906 to 1908 ft/s [National Earthquake Hazards Reduction Program (NEHRP) site classes C and D], because most sites were covered with soil of variable thickness. Based on these data, an NEHRP site-class map was developed for the Big Island. These new V(S) data will be a significant input into an update of the USGS statewide hazard maps and to the operation of ShakeMap on the island of Hawaii.George E. Brown, Jr. Network for Earthquake Engineering Simulation (NEES) under NSF CMS-0086605FEMA HSFEHQ-06-D-0162, HSFEHQ-04-D-0733U.S. Geological Survey, Department of the Interior 08HQGR0036Geotechnical Engineering Cente

Diphenyl Difluoroketone: A Potent Chemotherapy Candidate for Human Hepatocellular Carcinoma

Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 µM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 µM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G2/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB) pathway and the NF-κB–regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Field studies comparing SASW, beamforming and MASW test methods and characterization of geotechnical materials based on Vs

textEstimating S-wave velocities (Vs) from Rayleigh-wave velocities (VR) is widely used in field seismic testing for geotechnical engineering purposes. In this research, two widely used surface-wave methods, the Spectral-Analysis-of-Surface-Waves (SASW) and Multichannel-Analysis-of-Surface-Waves (MASW) methods, are evaluated and compared in field experiments. An experimental parametric study was undertaken of the SASW and MASW methods. Conventional seismic sources in the SASW method are sledge hammers, bulldozers and vibroseises. For MASW testing, sledge hammers and small shakers are usually used as the seismic sources. In this research, MASW testing was performed with traditional and non-traditional sources at a site owned by the City of Austin, Texas. Experimental dispersion curves and Vs profiles from SASW tests are used as references for the field parametric study with the MASW method. The source type, source offset, receiver spacing and number of receivers were varied to evaluate the impact of each variable on the field experimental dispersion curve. Two type of receivers, 1-Hz and 4.5-Hz natural-frequency geophones, were also compared in these tests. A second part of this research involved studying the use of characterizing geotechnical materials based on Vs. This work included two projects. The first project involved basalt on the Big Island of Hawaii. To develop empirical ground motion prediction models for the purpose of earthquake hazard mitigation and seismic design on the Big Island, the subsurface site conditions beneath 22 strong motion stations were investigated by SASW tests. Vs profiling was performed to depths of more than 100 ft. Vs30, the average Vs in the top 30 m, was also calculated to assign NEHRP site classes to different testing locations. Different materials, mainly thought to be stiff basalt, were characterized and grouped based on the Vs values. These groups were then compared with reference curves for sand and gravel (Menq, 2003) to differentiate the groups. The second project dealing with charactering geotechnical materials based on Vs involved of soil/rock profiles at a project site in British Columbia, Canada. The goals in terms of this research were to: (1) compare the Vs profiles from the different test locations to investigate the stiffnesses of different geologic materials, the variability in the material stiffnesses, and the estimated depth to bedrock, and (2) to compare the Vs profiles to existing geological and geotechnical information such as nearby boreholes, cone penetration tests and seismic cone penetration tests. Good agreement between SASW Vs profiles and boring records is expected when lateral variability at the site is low. However, when lateral variability is significant, then the difference between localized measurements, like borings and CPT results, and global measurements, like SASW Vs results, can further contribute to understanding the site conditions as shown at the site in British Columbia, Canada.Civil, Architectural, and Environmental Engineerin

Contrasting Electron and Hole Transfer Dynamics from CH(NH2)2PbI3 Perovskite Quantum Dots to Charge Transport Layers

In this work, the ultrafast transient absorption spectroscopy (TAs) was utilized to first investigate the charge transfer from the emerging FAPbI3 (FA = CH(NH2)2) perovskite quantum dots (PQDs) to charge transport layers. Specifically, we compared the TAs in pure FAPbI3 PQDs, PQDs grown with both electron and hole transfer layers (ETL and HTL), and PQDs with only ETL or HTL. The TA signals induced by photoexcited electrons decay much faster in PQDs samples with the ETL (~20 ps) compared to the pure FAPbI3 PQDs (>1 ns). These results reveal that electrons can effectively transport between coupled PQDs and transfer to the ETL (TiO2) at a time scale of 20 ps, much faster than the bimolecular charge recombination inside the PQDs (>1 ns), and the electron transfer efficiency is estimated to be close to 100%. In contrast, the temporal evolution of the TA signals in the PQDs with and without HTL exhibit negligible change, and no substantive hole transfer to the HTL (poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine], PTAA) occurs within 1 ns. The much slower hole transfer implies the further potential of increasing the overall photo-carrier conversion efficiency through enhancing the hole diffusion length and fine-tuning the coupling between the HTL and PQDs

Family Perception and 6-Month Symptomatic and Functioning Outcomes in Young Adolescents at Clinical High Risk for Psychosis in a General Population in China.

Given the difficulty of treating schizophrenia and other forms of psychosis, researchers have shifted focus to early detection and intervention of individuals at clinical high risk (CHR) for psychosis. Previous studies have shown that elements in family functioning could predict symptom outcome in CHR individuals. However, associations between self reported family functioning and symptom or functioning outcome of CHR individuals was rarely reported. Our study aimed to investigate the characteristics and the role of family functioning in the development of CHR individuals among young adolescents.A sample of 32 CHR individuals was recruited from 2800 university students. The characteristics of family perception were evaluated by both Family Assessment Device (FAD) and Family cohesion and adaptability evaluation Scale II (FACES II). 6 month follow up data was available with 25 of the recruited CHR individuals. Baseline socio-demographic characteristics and family functioning were compared between CHR and control group. We also measured the associations between different dimensions of perceived family functioning and both severity of prodromal symptoms and global functioning at baseline and 6-month follow up.CHR individuals showed more maladaptive family functioning compared to control in nearly all of the dimensions of FAD and FACES II except for Affective Involvement. Better Problem Solving and Affective Responsiveness predicted less severe positive and negative symptoms respectively. Family cohesion and adaptability were not only correlated with the baseline severity of general symptoms, but also positively associated with the general and disorganized symptom outcome.This study contributed preliminary evidence towards the associations between family perception and symptom outcome of CHR individuals. It also provided evidence for the importance of family interventions on CHR individuals

Structural insights into TSC complex assembly and GAP activity on Rheb.

Tuberous sclerosis complex (TSC) integrates upstream stimuli and regulates cell growth by controlling the activity of mTORC1. TSC complex functions as a GTPase-activating protein (GAP) towards small GTPase Rheb and inhibits Rheb-mediated activation of mTORC1. Mutations in TSC genes cause tuberous sclerosis. In this study, the near-atomic resolution structure of human TSC complex reveals an arch-shaped architecture, with a 2:2:1 stoichiometry of TSC1, TSC2, and TBC1D7. This asymmetric complex consists of two interweaved TSC1 coiled-coil and one TBC1D7 that spans over the tail-to-tail TSC2 dimer. The two TSC2 GAP domains are symmetrically cradled within the core module formed by TSC2 dimerization domain and central coiled-coil of TSC1. Structural and biochemical analyses reveal TSC2 GAP-Rheb complimentary interactions and suggest a catalytic mechanism, by which an asparagine thumb (N1643) stabilizes γ-phosphate of GTP and accelerate GTP hydrolysis of Rheb. Our study reveals mechanisms of TSC complex assembly and GAP activity

Structural insights into TSC complex assembly and GAP activity on Rheb.

Tuberous sclerosis complex (TSC) integrates upstream stimuli and regulates cell growth by controlling the activity of mTORC1. TSC complex functions as a GTPase-activating protein (GAP) towards small GTPase Rheb and inhibits Rheb-mediated activation of mTORC1. Mutations in TSC genes cause tuberous sclerosis. In this study, the near-atomic resolution structure of human TSC complex reveals an arch-shaped architecture, with a 2:2:1 stoichiometry of TSC1, TSC2, and TBC1D7. This asymmetric complex consists of two interweaved TSC1 coiled-coil and one TBC1D7 that spans over the tail-to-tail TSC2 dimer. The two TSC2 GAP domains are symmetrically cradled within the core module formed by TSC2 dimerization domain and central coiled-coil of TSC1. Structural and biochemical analyses reveal TSC2 GAP-Rheb complimentary interactions and suggest a catalytic mechanism, by which an asparagine thumb (N1643) stabilizes γ-phosphate of GTP and accelerate GTP hydrolysis of Rheb. Our study reveals mechanisms of TSC complex assembly and GAP activity

Tailoring phase alignment and interfaces via polyelectrolyte anchoring enables large-area 2D Perovskite solar cells

Ruddlesden–Popper phase 2D perovskite solar cells (PSCs) exhibit improved lifetime while still facing challenges such as phase alignment and up-scaling to module-level devices. Herein, polyelectrolytes are explored to tackle this issue. The contact between perovskite and hole-transport layer (HTL) is important for decreasing interfacial non-radiative recombination and scalable fabrication of uniform 2D perovskite films. Through exploring compatible butylamine cations, we first demonstrate poly(3-(4-carboxybutyl)thiophene-2,5-diyl)-butylamine (P3CT-BA) as an efficient HTL for 2D PSCs due to its great hydrophilicity, relatively high hole mobility and uniform surface. More importantly, the tailored P3CT-BA has an anchoring effect and acts as the buried passivator for 2D perovskites. Consequently, a best efficiency approaching 18¿% was achieved and we further first report large-area (2×3 cm2, 5×5 cm2) 2D perovskite minimodules with an impressive efficiency of 14.81¿% and 11.13¿%, respectively.Peer ReviewedPostprint (author's final draft