Nanoscale Analysis of Frozen Water by Atom Probe Tomography Using Graphene Encapsulation and Cryo-Workflows.

There has been an increasing interest in atom probe tomography (APT) to characterize hydrated and biological materials. A major benefit of APT compared to microscopy techniques more commonly used in biology is its combination of outstanding three-dimensional (3D) spatial resolution and mass sensitivity. APT has already been successfully used to characterize biominerals, revealing key structural information at the atomic scale, however there are many challenges inherent to the analysis of soft hydrated materials. New preparation protocols, often involving specimen preparation and transfer at cryogenic temperature, enable APT analysis of hydrated materials and have the potential to enable 3D atomic scale characterization of biological materials in the near-native hydrated state. In this study, samples of pure water at the tips of tungsten needle specimens were prepared at room temperature by graphene encapsulation. A comparative study was conducted where specimens were transferred at either room temperature or cryo-temperature and analyzed by APT by varying the flight path and pulsing mode. The differences between the analysis workflows are presented along with recommendations for future studies, and the compatibility between graphene coating and cryogenic workflows is demonstrated.

Integrating principles and tools of decision science into value-driven watershed planning for compensatory mitigation.

Several environmental policies strive to restore impaired ecosystems and could benefit from a consistent and transparent process-codeveloped with key stakeholders-to prioritize impaired ecosystems for restoration activities. The Clean Water Act, for example, establishes reallocation mechanisms to transfer ecosystem services from sites of disturbance to compensation sites to offset aquatic resource functions that are unavoidably lost through land development. However, planning for the prioritization of compensatory mitigation areas is often hampered by decision-making processes that fall into a myopic decision frame because they are not coproduced with stakeholders. In this study, we partnered with domain experts from the North Carolina Division of Mitigation Services to codevelop a real-world decision framework to prioritize catchments by potential for the development of mitigation projects following principles of a structured decision-making process and knowledge coproduction. Following an iterative decision analysis cycle, domain experts revised foundational components of the decision framework and progressively added complexity and realism as they gained additional insights or more information became available. Through the course of facilitated in-person and remote interactions, the codevelopment of a decision framework produced three main "breakthroughs" from the perspective of the stakeholder group: (a) recognition of the problem as a multiobjective decision driven by several values in addition to biogeophysical goals (e.g., functional uplift, restoring or enhancing lost functionality of ecosystems); (b) that the decision comprises a linked and sequential planning-to-implementation process; and (c) future risk associated with land-use and climate change must be considered. We also present an interactive tool for "on-the-fly" assessment of alternatives and tradeoff analysis, allowing domain experts to quickly test, react to, and revise prioritization strategies. The decision framework described in this study is not limited to the prioritization of compensatory mitigation activities across North Carolina but rather serves as a framework to prioritize a wide range of restoration, conservation, and resource allocation activities in similar environmental contexts across the nation.

The neoadjuvant rectal score and a novel magnetic resonance imaging based neoadjuvant rectal score are stage independent predictors of long-term outcome in locally advanced rectal cancer.

AIM: Neoadjuvant rectal (NAR) score is an early surrogate for longer-term outcomes in rectal cancer undergoing radiotherapy and resection. In an era of increasing organ preservation, resection specimens are not always available to calculate the NAR score. Post-treatment magnetic resonance imaging (MRI) re-staging of regression is subjective, limiting reproducibility. We explored the potential for a novel MRI-based NAR score (mrNAR) adapted from the NAR formula. METHODS: Locally advanced rectal cancer patients undergoing neoadjuvant therapy (nCRT) and surgery were retrospectively identified between 2008 and 2020 in a single cancer network. mrNAR was calculated by adapting the NAR formula, replacing pathological (p) stages with post-nCRT MR stages (ymr). Cox regression assessed relationships between clinicopathological characteristics, NAR and mrNAR with overall survival (OS) and recurrence-free survival (RFS). RESULTS: In total, 381 NAR and 177 mrNAR scores were calculated. On univariate analysis NAR related to OS (hazard ratio [HR] 2.05, 95% confidence interval [CI] 1.33-3.14, p = 0.001) and RFS (HR 2.52, 95% CI 1.77-3.59, p = 0.001). NAR 3-year OS <8 was 95.3%, 8-16 was 88.6% and >16 was 80%. mrNAR related to OS (HR 2.96, 95% CI 1.38-6.34, p = 0.005) and RFS (HR 2.99, 95% CI 1.49-6.00, p = 0.002). 3-year OS for mrNAR <8 was 96.2%, 8-16 was 92.4% and >16 was 78%. On multivariate analysis, mrNAR was a stage-independent predictor of OS and RFS. mrNAR corresponded to NAR score category in only 15% (positive predictive value 0.23) and 47.5% (positive predictive value 0.48) of cases for categories <8 and >16, respectively. CONCLUSIONS: Neoadjuvant rectal score is validated as a surrogate end-point for long-term outcomes. mrNAR categories do not correlate with NAR but have stage-independent prognostic value. mrNAR may represent a novel surrogate end-point for future neoadjuvant treatments that focus on organ preservation.

Point Density Variations in Airborne Lidar Point Clouds.

In spite of increasing point density and accuracy, airborne lidar point clouds often exhibit point density variations. Some of these density variations indicate issues with point clouds, potentially leading to errors in derived products. To highlight these issues, we provide an overview of point density variations and show examples in six airborne lidar point cloud datasets that we used in our topographic and geospatial modeling research. Using the published literature, we identified sources of point density variations and issues indicated or caused by these variations. Lastly, we discuss the reduction in point density variations using decimations, homogenizations, and their applicability.

Methods of Preparing Nanoscale Vitreous Ice Needles for High-Resolution Cryogenic Characterization.

New high-resolution imaging methods for biological samples such as atom probe tomography (APT), facilitated by the invention of laser-pulsed atom probes and cryo-transfer procedures, have recently emerged. However, ensuring the vitreous state of the fabricated aqueous needle-shaped APT samples remains a challenge despite it being crucial for characterizing biomolecules such as proteins and cellular architectures in their near-native state. Our work investigated three potential approaches: (1) open microcapillary (OMC) method, (2) high-pressure freezing method (HPF), and (3) graphene encapsulation method. Diffraction patterns of the needle specimens acquired by cryo-TEM have demonstrated the vitreous state of the ice needles, although limited to the tip regions, has been achieved with the three proposed approaches. With the capability to prepare vitreous ice needles from hydrated samples of up to ∼200 µm thickness (HPF), combined use of the three approaches opens new avenues for future near-atomic imaging of biological cells in their near-native state.

Protein Tyrosine Phosphatase Non-Receptor 11 (PTPN11/Shp2) as a Driver Oncogene and a Novel Therapeutic Target in Non-Small Cell Lung Cancer (NSCLC).

PTPN11 encodes the SHP2 protein tyrosine phosphatase that activates the mitogen-activated protein kinase (MAPK) pathway upstream of KRAS and MEK. PTPN11/Shp2 somatic mutations occur frequently in Juvenile myelomonocytic leukaemia (JMML); however, the role of mutated PTPN11 in lung cancer tumourigenesis and its utility as a therapeutic target has not been fully addressed. We applied mass-spectrometry-based genotyping to DNA extracted from the tumour and matched the normal tissue of 356 NSCLC patients (98 adenocarcinomas (LUAD) and 258 squamous cell carcinomas (LUSC)). Further, PTPN11 mutation cases were identified in additional cohorts, including TCGA, Broad, and MD Anderson datasets and the COSMIC database. PTPN11 constructs harbouring PTPN11 E76A, A72D and C459S mutations were stably expressed in IL-3 dependent BaF3 cells and NSCLC cell lines (NCI-H1703, NCI-H157, NCI-H1299). The MAPK and PI3K pathway activation was evaluated using Western blotting. PTPN11/Shp2 phosphatase activity was measured in whole-cell protein lysates using an Shp2 assay kit. The Shp2 inhibitor (SHPi) was assessed both in vitro and in vivo in a PTPN11-mutated cell line for improved responses to MAPK and PI3K targeting therapies. Somatic PTPN11 hotspot mutations occurred in 4/98 (4.1%) adenocarcinomas and 7/258 (2.7%) squamous cells of 356 NSCLC patients. Additional 26 PTPN11 hotspot mutations occurred in 23 and 3 adenocarcinomas and squamous cell carcinoma, respectively, across the additional cohorts. Mutant PTPN11 significantly increased the IL-3 independent survival of Ba/F3 cells compared to wildtype PTPN11 (p < 0.0001). Ba/F3, NCI-H1703, and NCI-H157 cells expressing mutant PTPN11 exhibited increased PTPN11/Shp2 phosphatase activity and phospho-ERK1/2 levels compared to cells expressing wildtype PTPN11. The transduction of the PTPN11 inactivating mutation C459S into NSCLC cell lines led to decreased phospho-ERK, as well as decreased phospho-AKT in the PTPN11-mutated NCI-H661 cell line. NCI-H661 cells (PTPN11-mutated, KRAS-wild type) were significantly more sensitive to growth inhibition by the PI3K inhibitor copanlisib (IC50: 13.9 ± 4.7 nM) compared to NCI-H1703 (PTPN11/KRAS-wild type) cells (IC50: >10,000 nM). The SHP2 inhibitor, in combination with the PI3K targeting therapy copanlisib, showed no significant difference in tumour development in vivo; however, this significantly prevented MAPK pathway induction in vitro (p < 0.0001). PTPN11/Shp2 demonstrated the in vitro features of a driver oncogene and could potentially sensitize NSCLC cells to PI3K inhibition and inhibit MAPK pathway activation following PI3K pathway targeting.

Optimizing Parameters for Using the Parallel Auditory Brainstem Response to Quickly Estimate Hearing Thresholds.

OBJECTIVES: Timely assessments are critical to providing early intervention and better hearing and spoken language outcomes for children with hearing loss. To facilitate faster diagnostic hearing assessments in infants, the authors developed the parallel auditory brainstem response (pABR), which presents randomly timed trains of tone pips at five frequencies to each ear simultaneously. The pABR yields high-quality waveforms that are similar to the standard, single-frequency serial ABR but in a fraction of the recording time. While well-documented for standard ABRs, it is yet unknown how presentation rate and level interact to affect responses collected in parallel. Furthermore, the stimuli are yet to be calibrated to perceptual thresholds. Therefore, this study aimed to determine the optimal range of parameters for the pABR and to establish the normative stimulus level correction values for the ABR stimuli. DESIGN: Two experiments were completed, each with a group of 20 adults (18-35 years old) with normal-hearing thresholds (≤20 dB HL) from 250 to 8000 Hz. First, pABR electroencephalographic (EEG) responses were recorded for six stimulation rates and two intensities. The changes in component wave V amplitude and latency were analyzed, as well as the time required for all responses to reach a criterion signal-to-noise ratio of 0 dB. Second, behavioral thresholds were measured for pure tones and for the pABR stimuli at each rate to determine the correction factors that relate the stimulus level in dB peSPL to perceptual thresholds in dB nHL. RESULTS: The pABR showed some adaptation with increased stimulation rate. A wide range of rates yielded robust responses in under 15 minutes, but 40 Hz was the optimal singular presentation rate. Extending the analysis window to include later components of the response offered further time-saving advantages for the temporally broader responses to low-frequency tone pips. The perceptual thresholds to pABR stimuli changed subtly with rate, giving a relatively similar set of correction factors to convert the level of the pABR stimuli from dB peSPL to dB nHL. CONCLUSIONS: The optimal stimulation rate for the pABR is 40 Hz but using multiple rates may prove useful. Perceptual thresholds that subtly change across rate allow for a testing paradigm that easily transitions between rates, which may be useful for quickly estimating thresholds for different configurations of hearing loss. These optimized parameters facilitate expediency and effectiveness of the pABR to estimate hearing thresholds in a clinical setting.

Use of exhaled breath condensate (EBC) in the diagnosis of SARS-COV-2 (COVID-19).

False negatives from nasopharyngeal swabs (NPS) using reverse transcriptase PCR (RT-PCR) in SARS-CoV-2 are high. Exhaled breath condensate (EBC) contains lower respiratory droplets that may improve detection. We performed EBC RT-PCR for SARS-CoV-2 genes (E, S, N, ORF1ab) on NPS-positive (n=16) and NPS-negative/clinically positive COVID-19 patients (n=15) using two commercial assays. EBC detected SARS-CoV-2 in 93.5% (29/31) using the four genes. Pre-SARS-CoV-2 era controls (n=14) were negative. EBC was positive in NPS negative/clinically positive patients in 66.6% (10/15) using the identical E and S (E/S) gene assay used for NPS, 73.3% (11/15) using the N/ORF1ab assay and 14/15 (93.3%) combined.

Understanding Reentrance in Frustrated Magnets: The Case of the Er_{2}Sn_{2}O_{7} Pyrochlore.

Reentrance, the return of a system from an ordered phase to a previously encountered less-ordered one as a controlled parameter is continuously varied, is a recurring theme found in disparate physical systems, yet its microscopic cause is often not investigated thoroughly. Here, through detailed characterization and theoretical modeling, we uncover the microscopic mechanism behind reentrance in the strongly frustrated pyrochlore antiferromagnet Er_{2}Sn_{2}O_{7}. We use single crystal heat capacity measurements to expose that Er_{2}Sn_{2}O_{7} exhibits multiple instances of reentrance in its magnetic field B vs temperature T phase diagram for magnetic fields along three cubic high symmetry directions. Through classical Monte Carlo simulations, mean field theory, and classical linear spin-wave expansions, we argue that the origins of the multiple occurrences of reentrance observed in Er_{2}Sn_{2}O_{7} are linked to soft modes. These soft modes arise from phase competition and enhance thermal fluctuations that entropically stabilize a specific ordered phase, resulting in an increased transition temperature for certain field values and thus the reentrant behavior. Our work represents a detailed examination into the mechanisms responsible for reentrance in a frustrated magnet and may serve as a template for the interpretation of reentrant phenomena in other physical systems.

Evaluating online and tangible interfaces for engaging stakeholders in forecasting and control of biological invasions.

Ecological forecasts will be best suited to inform intervention strategies if they are accessible to a diversity of decision-makers. Researchers are developing intuitive forecasting interfaces to guide stakeholders through the development of intervention strategies and visualization of results. Yet, few studies to date have evaluated how user interface design facilitates the coordinated, cross-boundary management required for controlling biological invasions. We used a participatory approach to develop complementary tangible and online interfaces for collaboratively forecasting biological invasions and devising control strategies. A diverse group of stakeholders evaluated both systems in the real-world context of controlling sudden oak death, an emerging forest disease killing millions of trees in California and Oregon. Our findings suggest that while both interfaces encouraged adaptive experimentation, tangible interfaces are particularly well suited to support collaborative decision-making. Reflecting on the strengths of both systems, we suggest workbench-style interfaces that support simultaneous interactions and dynamic geospatial visualizations.

Iteratively forecasting biological invasions with PoPS and a little help from our friends.

Ecological forecasting has vast potential to support environmental decision making with repeated, testable predictions across management-relevant timescales and locations. Yet resource managers rarely use co-designed forecasting systems or embed them in decision making. Although prediction of planned management outcomes is particularly important for biological invasions to optimize when and where resources should be allocated, spatial-temporal models of spread typically have not been openly shared, iteratively updated, or interactive to facilitate exploration of management actions. We describe a species-agnostic, open-source framework - called the Pest or Pathogen Spread (PoPS) Forecasting Platform - for co-designing near-term iterative forecasts of biological invasions. Two case studies are presented to demonstrate that iterative calibration yields higher forecast skill than using only the earliest-available data to predict future spread. The PoPS framework is a primary example of an ecological forecasting system that has been both scientifically improved and optimized for real-world decision making through sustained participation and use by management stakeholders.

Characterization of the Inflammatory Response to Severe COVID-19 Illness.

Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood.Objectives: To define the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness.Methods: Levels of IL-1ß, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVIDstable patients), patients with COVID-19 requiring ICU admission (COVIDICU patients), and patients with severe community-acquired pneumonia requiring ICU support (CAPICU patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated.Measurements and Main Results: IL-1ß, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable patients, and demonstrated higher levels of IL-1ß, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P < 0.0001).Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.

Novel behavioral interventions to improve long-term weight loss: A randomized trial of acceptance and commitment therapy or self-regulation for weight loss maintenance.

Maintenance of weight loss is hard to achieve, and novel interventions are needed to improve long-term outcomes. In this pilot randomized controlled trial, N = 188 participants received an online, 12-week weight loss intervention and N = 102 who lost ≥ 5% were then randomly assigned to a 1-day, 5-h workshop based on Acceptance and Commitment Therapy (ACT), Self-Regulation (SR), or no workshop (Control) with 3 months of limited email follow-up. Assessments were conducted at baseline, 3, 6, 12, 18, and 24 months. The primary outcome was percent weight change; secondary outcomes were weight-related experiential avoidance and health values-consistent behavior. ACT had greater overall weight loss (-7.18%, SE = 1.33) when compared to Control (-1.15%, SE = 1.50; p = .03). Post hoc analyses showed that ACT had significantly greater weight losses than Control (6.11%, ß = -2.03, p = .048) among those with lower initial weight loss (5-7%), and significantly greater weight loss than SR (6.19%, ß = -1.77, p = .05) among those with the highest initial weight losses (10% +). There is potential for continuing to develop ACT in a limited interventionist-contact format with modifications. This pilot study represents an innovative model for behavioral weight loss by reversing the typical treatment intensity model with the aim of providing interventionist support during a critical period after initial weight loss. REGISTRATION: Clinicaltrials.org #NCT02156752 https://www.clinicaltrials.gov/ct2/show/NCT02156752 .

Spatial alignment between faces and voices improves selective attention to audio-visual speech.

The ability to see a talker's face improves speech intelligibility in noise, provided that the auditory and visual speech signals are approximately aligned in time. However, the importance of spatial alignment between corresponding faces and voices remains unresolved, particularly in multi-talker environments. In a series of online experiments, we investigated this using a task that required participants to selectively attend a target talker in noise while ignoring a distractor talker. In experiment 1, we found improved task performance when the talkers' faces were visible, but only when corresponding faces and voices were presented in the same hemifield (spatially aligned). In experiment 2, we tested for possible influences of eye position on this result. In auditory-only conditions, directing gaze toward the distractor voice reduced performance, but this effect could not fully explain the cost of audio-visual (AV) spatial misalignment. Lowering the signal-to-noise ratio (SNR) of the speech from +4 to -4 dB increased the magnitude of the AV spatial alignment effect (experiment 3), but accurate closed-set lipreading caused a floor effect that influenced results at lower SNRs (experiment 4). Taken together, these results demonstrate that spatial alignment between faces and voices contributes to the ability to selectively attend AV speech.

Three-Dimensional Chemical Mapping of a Single Protein in the Hydrated State with Atom Probe Tomography.

Unravelling the three-dimensional structures and compositions of biological macromolecules sheds light on their functions and also contributes to the design of future biochemical compounds and processes. Atom probe tomography (APT) is demonstrated in this research as a new and effective approach to explore the structure and chemical composition of a single protein in the hydrated state. By introducing graphene encapsulation, proteins in solution can be immobilized on a metal specimen tip, with an end radius in the range of 50 nm to allow field ionization and evaporation. Using a ferritin particle as an example, analysis of the mass spectrum and reconstructed 3D chemical maps at near-atomic resolution acquired from APT reveals the core consisting of iron and iron oxides, the peptide shell containing amino acids, and the interior interface between the iron core and the peptide shell. The quantitative distribution and proportion of iron isotopes from a single ferritin core have been determined for the first time, as well as identification of the possible sites of amino acids inside the protein shell. The complete experimental protocol is straightforward and lays a foundation for future exploration of various macromolecules in a controlled environment.

Accelerated ageing profile in inflammatory arthritis is unique and tissue compartment specific.

Rheumatoid arthritis is prevalent in more than 1% of the global population, with the highest occurrence between ages 35 and 50, which places a huge burden on the economy. Drug discovery for the prevention of this chronic disease is; therefore, a priority. It is known that subclinical progression of many chronic non-communicable diseases is exacerbated via accelerated ageing, a pro-inflammatory phenotype shift. However, rheumatoid arthritis additionally has significant humoral immune activation, inflammatory signalling-and thus the accelerated ageing profile-may differ from other chronic inflammatory diseases. The current study simulated inflammatory arthritis onset in a collagen-induced arthritis (CIA) rodent model, to characterise the redox and inflammatory profile at the onset of clinical symptoms, in different tissues, in the presence and absence of preventative antioxidant treatment. The data illustrate that an increased free radical level are evident already very early on in RA disease progression. Furthermore, oxidative stress seems to somewhat precede a significant pro-inflammatory state, perhaps due to humoral immune activation. Our data across different compartments further suggest that the compensatory increase in endogenous antioxidant activity is gradually exhausted at a different pace, with the liver showing the first signs of oxidant damage, even before significant evidence exist in circulation. The current data further suggest that preventative antioxidant intervention may have a sparing effect on endogenous antioxidant mechanisms and preserve telomere length to delay disease progression-or at least the accelerated ageing known to exacerbate RA symptoms-although it did not seem to have a significant direct effect on the autoimmune activity.

Novel Strongly Spin-Orbit Coupled Quantum Dimer Magnet: Yb_{2}Si_{2}O_{7}.

The quantum dimer magnet (QDM) is the canonical example of quantum magnetism. The QDM state consists of entangled nearest-neighbor spin dimers and often exhibits a field-induced triplon Bose-Einstein condensate (BEC) phase. We report on a new QDM in the strongly spin-orbit coupled, distorted honeycomb-lattice material Yb_{2}Si_{2}O_{7}. Our single crystal neutron scattering, specific heat, and ultrasound velocity measurements reveal a gapped singlet ground state at zero field with sharp, dispersive excitations. We find a field-induced magnetically ordered phase reminiscent of a BEC phase, with exceptionally low critical fields of H_{c1}∼0.4 and H_{c2}∼1.4 T. Using inelastic neutron scattering in an applied magnetic field we observe a Goldstone mode (gapless to within δE=0.037 meV) that persists throughout the entire field-induced magnetically ordered phase, suggestive of the spontaneous breaking of U(1) symmetry expected for a triplon BEC. However, in contrast to other well-known cases of this phase, the high-field (µ_{0}H≥1.2 T) part of the phase diagram in Yb_{2}Si_{2}O_{7} is interrupted by an unusual regime signaled by a change in the field dependence of the ultrasound velocity and magnetization, as well as the disappearance of a sharp anomaly in the specific heat. These measurements raise the question of how anisotropy in strongly spin-orbit coupled materials modifies the field induced phases of QDMs.

Quantum Spin Ice Dynamics in the Dipole-Octupole Pyrochlore Magnet Ce_{2}Zr_{2}O_{7}.

Neutron scattering measurements on the pyrochlore magnet Ce_{2}Zr_{2}O_{7} reveal an unusual crystal field splitting of its lowest J=5/2 multiplet, such that its ground-state doublet is composed of m_{J}=±3/2, giving these doublets a dipole-octupole (DO) character with local Ising anisotropy. Its magnetic susceptibility shows weak antiferromagnetic correlations with θ_{CW}=-0.4(2) K, leading to a naive expectation of an all-in, all-out ordered state at low temperatures. Instead, our low-energy inelastic neutron scattering measurements show a dynamic quantum spin ice state, with suppressed scattering near |Q|=0, and no long-range order at low temperatures. This is consistent with recent theory predicting symmetry-enriched U(1) quantum spin liquids for such DO doublets decorating the pyrochlore lattice. Finally, we show that disorder, especially oxidation of powder samples, is important in Ce_{2}Zr_{2}O_{7} and could play an important role in the low-temperature behavior of this material.

Aberrant miR-145-5p/ß-catenin signal impairs osteocyte function in adolescent idiopathic scoliosis.

Recently, noncoding RNAs have been thought to play important roles in the sporadic occurrence of spinal deformity of adolescent idiopathic scoliosis (AIS). As a prognostic factor for curve progression, low bone mass has been hypothesized to crosstalk with AIS pathogenesis. Abnormal osteoblasts activities are reported in AIS without a clear mechanism. In this study, bone biopsies from patients with AIS and control subjects and the primary osteoblasts derived from those samples were used to identify the potential microRNA (miRNA) candidates that interfere with osteoblasts and osteocytes function. Microarray analysis identified miRNA-145-5p (miR-145) as a potential upstream regulator. miR-145 and ß-catenin mRNA ( CTNNB1) were overexpressed in AIS bone tissues and primary osteoblasts, and their expression correlated positively in AIS. Knockdown of miR-145 restored impaired osteocyte activity through the down-regulation of active ß-catenin expression and its transcriptional activity. Significant negative correlations between circulating miR-145 and serum sclerostin, osteopontin, and osteoprotegerin were noted in patients with AIS, which was in line with our cellular findings. This is the first study to demonstrate the effect of aberrant miRNA expression and its effect on osteocyte function in AIS, which may contribute to the low bone mass. Our findings also provide insight into the development of circulating microRNAs as a bone quality biomarker or even a prognostic biomarker for AIS.-Zhang, J., Chen, H., Leung, R. K. K., Choy, K. W., Lam, T. P., Ng, B. K. W., Qiu,Y., Feng, J. Q., Cheng, J. C. Y., Lee, W. Y. W. Aberrant miR-145-5p/ß-catenin signal impairs osteocyte function in adolescent idiopathic scoliosis.

Selective Recovery of Rare Earth Elements from Coal Fly Ash Leachates Using Liquid Membrane Processes.

Coal combustion residues and other geological waste materials have been proposed as a resource for rare earth elements (REEs, herein defined as the 14 stable lanthanides, yttrium, and scandium). The extraction of REEs from residues often generate acidified leachates that require highly selective separation methods to recover the REEs from other major soluble ions in the leachates. Here, we studied two liquid membrane processes (liquid emulsion membranes, LEM, and supported liquid membranes, SLM) and compared them to standard solvent extraction techniques for selective recovery and concentration of REEs from a leachate of coal fly ash. All separation methods involved an organic solution of di(2-ethylhexyl)phosphoric acid dissolved in kerosene or mineral oil and an acid strippant solution of 5 M nitric acid for the liquid-based separations. The LEM configuration, which separated REEs by immersing an acid-in-oil emulsion in the ash leachate, resulted in similar recovery percentages of individual REEs as the conventional solvent extraction approach. The recovery of REEs in the SLM configuration, which involved the impregnation of the solvent in a hydrophobic membrane, was slower than the LEM process. However, the SLM process was notably more selective for the heavy (and higher value) REEs, while the conventional extraction and LEM processes were more selective for the light REEs. A flux-based model of the extraction processes suggested that recovery rates were limited by REE affinity for the solvent chelator in the SLM, while the rates of REEs separation via LEM were limited by diffusive mass transfer across the liquid membrane. Altogether, these results help to identify specific steps in the recovery process that future work should target in the development of scalable liquid membrane separations for REE recovery.