The center of the San Joaquin Valley is one of the most productive agricultural regions in the US. Farmers rely heavily on surface-water diversions to meet irrigation water demand. However, the 2007–2010 and 2012–2017 droughts have caused strong increases in groundwater pumping causing land subsidence with strong variability in location, magnitude (total subsidence) and rate of subsidence. In this study, we try to understand what caused these variations. We focus our analyses on three areas: (i) the Westland water district where subsidence was very small during the two drought periods, (ii) ‘El Nido’ area where the greatest subsidence rate was monitored from 2008 to 2010, and (iii) the’ Kings-Tulare counties’ area where the subsidence was small during the 2008–2010 and the largest during 2015–2017 droughts. Our main finding is that land subsidence is located in areas where the water demand for agriculture and the density of groundwater wells is the highest, whereas the rate of subsidence is strongly affected the amount of local and imported surface water and by groundwater resources. Based on these simple observations, we propose using continuous satellite-based ground deformation monitoring and geomechanical modeling to (i) localize areas most prone for future subsidence and (ii) to estimate and manage groundwater resources.

While cloud-resolving models can explicitly simulate the details of small-scale storm formation and morphology, these details are often ignored by climate models for lack of computational resources. Here, we explore the potential of generative modeling to cheaply recreate small-scale storms by designing and implementing a Variational Autoencoder (VAE) that performs structural replication, dimensionality reduction, and clustering of high-resolution vertical velocity fields. Trained on ∼6 · 106 samples spanning the globe, the VAE successfully reconstructs the spatial structure of convection, performs unsupervised clustering of convective organization regimes, and identifies anomalous storm activity, confirming the potential of generative modeling to power stochastic parameterizations of convection in climate models.

Range change data, obtained from Synthetic Aperture Radar satellites, form the basis for estimates of aquifer volume change in California's Central Valley. The estimation algorithm incorporates a function penalizing changes far from known well locations, linking the aquifer volume changes to agricultural, industrial, and municipal pumping within the Tulare basin. We show that the range changes are compatible with the hypothesis that the source of aquifer volume changes are variations in effective pressure around documented wells. Specifically, inclusion of the well distance penalty does not degrade the fit to the observations, inversions with and without it both give variance reductions of 99.6%. The patterns of aquifer volume change vary significantly from the drought year, between October 2015 and October 2016, to a wet year in 2017, and into 2018, a year with near average rainfall. The 2.3 million acre-feet of estimated volume reduction, a lower bound on the amount of water extracted from the basin between October 2015 and 2016, agrees with independent estimates of 1.8 and 2.3 million acre-feet. The aquifer volume reduction is also compatible with a loss of 3.1 km³ (2.5 million acre-feet) in groundwater volume derived from Gravity Recovery and Climate Experiment (GRACE) satellite data.

Augmented reality (AR) devices, as smart glasses, enable users to see both the real world and virtual images simultaneously, contributing to an immersive experience in interactions and visualization. Recently, to reduce the size and weight of smart glasses, waveguides incorporating holographic optical elements in the form of advanced grating structures have been utilized to provide light-weight solutions instead of bulky helmet-type headsets. However current waveguide displays often have limited display resolution, efficiency and field-of-view, with complex multi-step fabrication processes of lower yield. In addition, current AR displays often have vergence-accommodation conflict in the augmented and virtual images, resulting in focusing-visual fatigue and eye strain. Here we report metasurface optical elements designed and experimentally implemented as a platform solution to overcome these limitations. Through careful dispersion control in the excited propagation and diffraction modes, we design and implement our high-resolution full-color prototype, via the combination of analytical-numerical simulations, nanofabrication and device measurements. With the metasurface control of the light propagation, our prototype device achieves a 1080-pixel resolution, a field-of-view more than 40°, an overall input-output efficiency more than 1%, and addresses the vergence-accommodation conflict through our focal-free implementation. Furthermore, our AR waveguide is achieved in a single metasurface-waveguide layer, aiding the scalability and process yield control.

We aimed to replicate the association of the IVS3-35A>G polymorphism in the activin receptor-like kinase (ACVRL) 1 gene and the 207G>A polymorphism in the endoglin (ENG) gene with sporadic brain arteriovenous malformations (BAVM) in Dutch BAVM patients. In addition, we assessed whether these polymorphisms contribute to the risk of BAVM in patients with hereditary haemorrhagic telangiectasia type 1 (HHT1). We genotyped 143 Dutch sporadic BAVM patients and 360 healthy volunteers for four variants in the ACVRL1 gene including IVS3-35A>G and two variants in the ENG gene including 207G>A. Differences in allele and genotype frequencies between sporadic BAVM patients and controls and their combined effect were analysed with a likelihood ratio test. Furthermore, we compared the allele and genotype frequencies between 24 HHT1 patients with a BAVM with those of a relative with HHT1 without a BAVM in a matched pair analysis using Wilcoxon signed rank test. No significant differences in allele frequency were found between sporadic BAVM cases and controls or between HHT1 patients with and without BAVM for any of the polymorphisms or the combination of ACVRL1 and ENG polymorphisms. Meta-analysis of the current and the two previous studies for the ACVRL1 IVS3-35A polymorphism showed a persisting association between the ACVRL1 IVS3-35A polymorphism and risk of sporadic BAVM (odds ratio, 1.86; 95% CI: 1.32-2.61, p<0.001). We did not replicate the previously found association between a polymorphism in ACVRL1 IVS3-35A>G and BAVM in Dutch patients. However, meta-analysis did not rule out a possible effect.

Subsidence induced by groundwater depletion is a grave problem in many regions around the world, leading to a permanent loss of groundwater storage within an aquifer and even producing structural damage at the Earth's surface. California's Tulare Basin is no exception, experiencing about a meter of subsidence between 2015 and 2020. However, understanding the relationship between changes in groundwater volumes and ground deformation has proven difficult. We employ surface displacement measurements from Interferometric Synthetic Aperture Radar (InSAR) and gravimetric estimates of terrestrial water storage from the Gravity Recovery and Climate Experiment (GRACE) satellite pair to characterize the hydrological dynamics within the Tulare basin. The removal of the long-term aquifer compaction from the InSAR time series reveals coherent short-term variations that correlate with hydrological features. For example, in the winter of 2018-2019 uplift is observed at the confluence of several rivers and streams that drain into the southeastern edge of the basin. These observations, combined with estimates of mass changes obtained from the orbiting GRACE satellites, form the basis for imaging the monthly spatial variations in water volumes. This approach facilitates the quick and effective synthesis of InSAR and gravimetric datasets and will aid efforts to improve our understanding and management of groundwater resources around the world.

This report constitutes the final report for Calendar Year 2001 (CY01) under Contract Number NAS2-99072 for the third year of a three-year research project entitled “Development of Fast-Time Simulation Techniques to Model Safety Issues in the National Airspace System.”  The objective of this research is to investigate and develop techniques to enable NAS fast-time simulation modeling to be useful for conducting safety analysis. The research efforts focus on examining the type of safety issues that could be appropriately modeled by fast-time simulations and developing, testing, and demonstrating human behavioral modules and data analysis routines that would need to be incorporated into fast-time simulations in order to predict the safety effects of changes in procedures or technologies and to support risk assessment.

Graphene is a powerful playground for studying a plethora of quantum phenomena. One of the remarkable properties of graphene arises when it is strained in particular geometries and the electrons behave as if they were under the influence of a magnetic field. Previously, these strain-induced pseudomagnetic fields have been explored on the nano- and micrometer-scale using scanning probe and transport measurements. Heteroepitaxial strain, in contrast, is a wafer-scale engineering method. Here, we show that pseudomagnetic fields can be generated in graphene through wafer-scale epitaxial growth. Shallow triangular nanoprisms in the SiC substrate generate strain-induced uniform fields of 41 T, enabling the observation of strain-induced Landau levels at room temperature, as detected by angle-resolved photoemission spectroscopy, and confirmed by model calculations and scanning tunneling microscopy measurements. Our work demonstrates the feasibility of exploiting strain-induced quantum phases in two-dimensional Dirac materials on a wafer-scale platform, opening the field to new applications.

Adaptation is key for survival as vector-borne pathogens transmit between the arthropod and vertebrate, and temperature change is an environmental signal inducing alterations in gene expression of tick-borne spirochetes. While plasmids are often associated with adaptation, complex genomes of relapsing fever spirochetes have hindered progress in understanding the mechanisms of vector colonization and transmission. We utilized recent advances in genome sequencing to generate the most complete version of the Borrelia turicatae 150 kb linear megaplasmid (lp150). Additionally, a transcriptional analysis of open reading frames (ORFs) in lp150 was conducted and identified regions that were up-regulated during in vitro cultivation at tick-like growth temperatures (22°C), relative to bacteria grown at 35°C and infected murine blood. Evaluation of the 3' end of lp150 identified a cluster of ORFs that code for putative surface lipoproteins. With a microbe's surface proteome serving important roles in pathogenesis, we confirmed the ORFs expression in vitro and in the tick compared to spirochetes infecting murine blood. Transcriptional evaluation of lp150 indicates the plasmid likely has essential roles in vector colonization and/or initiating mammalian infection. These results also provide a much needed transcriptional framework to delineate the molecular mechanisms utilized by relapsing fever spirochetes during their enzootic cycle.

Background

Although super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice, many different LPV/r dosing strategies are applied due to poor availability of pediatric separate ritonavir formulations needed to superboost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB) treatment.

Methods

This was a 2-arm pharmacokinetic substudy nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB treatment; during rifampicin cotreatment, they received double-dosed (ratio 8:2) or semisuperboosted LPV/r (adding a ritonavir 100 mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r.

Results

In total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin cotreatment (5 received double-dosed and 4 semisuperboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0 kg (5.2-6.8), and 10/14 were male. Of those receiving rifampicin, 6/9 infants (67%) had LPV Ctrough <1.0 mg/L compared with 1/5 (20%) in the control arm. LPV apparent oral clearance was 3.3-fold higher for infants receiving rifampicin.

Conclusion

Double-dosed or semisuperboosted LPV/r for infants aged 1-12 months receiving rifampicin resulted in substantial proportions of subtherapeutic LPV levels. There is an urgent need for data on alternative antiretroviral regimens in infants with HIV/TB coinfection, including twice-daily dolutegravir.