Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for a climate-driven hydrologic regime shift in the Canadian Columbia Basin

Water resources from the Columbia River Basin are intensely used for domestic, agricultural, industrial and hydroelectric generation needs. Water availability in the Pacific Northwest is influenced by several ocean–atmosphere modes of climate variability that occur in the Pacific Ocean. Climate change has the potential to alter these relationships and influence both the volume and timing of streamflow in the snowmelt-dominated tributaries to the Columbia River. Here, the historical influences of climate variability and recent climate warming on the volume and timing of streamflow for 40 tributary streams in the Columbia River Basin of Canada were evaluated. Regional relationships were found between streamflow and several Pacific Ocean climate indices, including the already established relationships with the Pacific Decadal Oscillation (PDO) and El Nino/Southern Oscillation (ENSO). However, in recent decades the statistical relationship between streamflow and climate indices has become weaker, which has implications for managers using these indices as decision-making tools. A comparison of the average annual streamflow for the cool PDO phase, which occurred from 1947 to 1976, to the more recent cool phase from 1999 to 2011 indicates a 11% decline across the Canadian portion of the basin. Removing the influence of these climate indices on historical streamflow reveals decreases in the residual streamflow beginning sometime in the 1980s. The potential role of increased temperatures on streamflow was investigated, and statistically significant relationships between decreased streamflow and increased temperatures in the summer months were found, particularly with the number of days over 18°C. The results suggest that climate change may be altering the historical relationship between climate indices and streamflow in the Canadian portion of the Columbia Basin.
Engineering hydrophobicity and manufacturability for optimized biparatopic antibody–drug conjugates targeting c-MET

ABSTRACT Optimal combinations of paratopes assembled into a biparatopic antibody have the capacity to mediate high-grade target cross-linking on cell membranes, leading to degradation of the target, as well as antibody and payload delivery in the case of an antibody-drug conjugate (ADC). In the work presented here, molecular docking suggested a suitable paratope combination targeting c-MET, but hydrophobic patches in essential binding regions of one moiety necessitated engineering. In addition to rational design of HCDR2 and HCDR3 mutations, site-specific spiking libraries were generated and screened in yeast and mammalian surface display approaches. Comparative analyses revealed similar positions amendable for hydrophobicity reduction, with a broad combinatorial diversity obtained from library outputs. Optimized variants showed high stability, strongly reduced hydrophobicity, retained affinities supporting the desired functionality and enhanced producibility. The resulting biparatopic anti-c-MET ADCs were comparably active on c-MET expressing tumor cell lines as REGN5093 exatecan DAR6 ADC. Structural molecular modeling of paratope combinations for preferential inter-target binding combined with protein engineering for manufacturability yielded deep insights into the capabilities of rational and library approaches. The methodologies of in silico hydrophobicity identification and sequence optimization could serve as a blueprint for rapid development of optimal biparatopic ADCs targeting further tumor-associated antigens in the future.
Prograde histories in high-P to ultra-high-P metamorphic rocks from Tibet and northern India

☆ Mineral abbreviations given follow Kretz (1983). ⁎ Corresponding author. Tel. : +61 2 93518199. E-mail address: t.chapman@sydney.edu. au (T. Chapman). http://dx.doi. org/10.1016/j.lithos. 2014.11. 019 0024-4937/© 2014 Elsevier B.V. All rights reserved.
Plant Sources of Propolis: An Update from a Chemist's Point of View

The newest developments in research on propolis plant sources are summarized. Special attention is paid to data based on reliable chemical evidence including comparison between propolis samples and plant material, and on well-documented bee behavior. A number of new proved propolis source plants are listed. Hypothetical sources, suggested as a result of comparison of propolis chemical composition and literature data about particular plants are also discussed.
Limited Research Investigating the Added Value of MRI in Predicting Future Cognitive Morbidity in Survivors of Paediatric Brain Tumours: A Call to Action for Clinical Neuroimaging Researchers

Survivors of pediatric brain tumour patients are at high risk of cognitive morbidity. There is clinical benefit in being able to reliably predict, at the individual patient level, whether a patient will experience these difficulties or not, the degree of impairment, and the domains affected. Whilst established risk factors exist, quantitative analysis of MRI could provide added predictive value towards this goal, above and beyond existing clinical risk models. The current systematic review aims to answer the question; Do MRI markers predict future cognitive functioning in pediatric brain tumour survivors? Studies of pediatric brain tumour patients which test the value of MRI variables in predicting later neuropsychological outcomes were searched up to July 2022. Only included were studies where MRI scans were acquired at an earlier timepoint and used to predict a child's performance on cognitive tests at a later timepoint. Surprisingly few studies were identified by the search process which specifically investigated MRI measures of cerebellar and white matter damage as features in predicting cognitive outcomes. However, the important finding of this review is that the current literature is limited and those identified had small sample sizes and were rated as poor quality for the purposes of prediction. Overall, current findings are at high risk of bias and thus the quality and impact of conclusions are limited. Given the significant impact for this clinical population that predictive models would enable, the current review affirms the need for a call-to-action for medical imaging researchers in pediatric neuro-oncology.
Alzheimer's Disease biological PET staging using plasma p217+tau

Background: Plasma phospho-tau biomarkers, such as p217+tau, excel at identifying Alzheimer's Disease (AD) neuropathology. However, questions remain regarding their capacity to inform AD biological PET stages at group level and maintain the same precision at individual patient level. Method: Participants included 248 cognitively unimpaired (CU) and 227 cognitively impaired (CI) individuals, with Janssen plasma p217+tau Simoa assay, 18F-NAV4694 A{beta} PET (A) and 18F-MK6240 tau PET (T) data. Biological PET stages were defined based on the draft NIA-AA Revised Criteria (July 2023): Initial (A+T-), Early (A+TMTL+), Intermediate (A+TMOD+), and Advanced (A+THIGH+). We used thresholds for A+ of 25 Centiloid and for THIGH of 80 Centaur (2.68 SUVRtemporo-parietal). Adding an A-T- stage for comparison, we assessed the performance of p217+tau in discriminating between these stages at the group level using Receiver Operating Characteristic (ROC) analysis and at the individual level using logistic regression. Results: Plasma p217+tau concentrations increased across the stages, with significant differences between them, except for the Initial and Early stages. Screening for Advanced (vs. lower stages), combined Intermediate/Advanced (vs. lower stages), or all stages (vs. A-T-), p217+tau showed good group-level discriminations (AUC 0.91, 0.92 and 0.92; CI only: AUC 0.83, 0.89, 0.93, respectively). At the individual level, the likelihood of PET stage vs. p217+tau level showed good discrimination of A-T- vs any A+ stage and of combined Intermediate/Advanced disease stage vs lower stages in the CI. Conclusion: In addition to accurately screening for A+ individuals, plasma p217+tau shows promise for separating persons with either Intermediate or Advanced stage AD from those at a lower stage, providing prognostic information and informing better selection for trials and disease modifying therapies.
Reannotation of the zebra finch genome reveals undiscovered transcriptional complexity

The zebra finch has become a paradigmatic model system to mechanistically investigate vocal communication from genes to behavior. Here, we report 1) a comprehensive map of the polyadenylated fraction of the transcriptome of the male zebra finch telencephalon at two ages, during the song learning phase at 50 days and when fully adult at 2 years as well as 2) as an expanded and refined annotation of the zebra finch genome based on our transcriptome data. Using high‐throughput next generation sequencing of paired‐end strand‐ specific cDNA fragments, we detected over 50% of the annotated protein coding transcripts (ENSEMBL v.55) in the telencephalon at both stages. We exploited the information gained from the paired‐end sequence reads and from reads falling onto splice junctions to update the existing annotation (ENS55) with new transcript structures and alternative splicing events. The dataset allowed to refine 2822 of the available gene models by extending them in the 3’‐UTR and to detect 11391 undiscovered transcriptional units in non‐coding regions. Our results illustrate the value of continuously incorporating new transcriptional evidence into existing annotations.
RhoA activation promotes glucose uptake to elevate proliferation in MAPK inhibitor resistant melanoma cells

Cutaneous melanomas harboring a B-RafV600E mutation are treated with immune check point inhibitors or kinase inhibitor combination therapies relying on MAPK inhibitors (MAPKi) Dabrafenib and Trametinib (Curti and Faries, 2021). However, cells become resistant to treatments over the timespan of a few months. Resistance to MAPKi has been associated with adoption of an aggressive amoeboid phenotype characterized by elevated RhoA signaling, enhanced contractility and thick cortical filamentous actin (F-actin) structures (Kim et al., 2016; Misek et al., 2020). Targeting active RhoA through Rho-kinase (ROCK) inhibitors, either alone or in combination with immunotherapies, reverts MAPKi-resistance (Misek et al., 2020; Orgaz et al., 2020). Yet, the mechanisms for this behavior remain largely unknown. Given our recent findings of cytoskeleton’s role in cancer cell proliferation (Mohan et al., 2019), survival (Weems et al., 2023), and metabolism (Park et al., 2020), we explored possibilities by which RhoA-driven changes in cytoskeleton structure may confer resistance. We confirmed elevated activation of RhoA in a panel of MAPKi-resistant melanoma cell lines, leading to a marked increase in the presence of contractile F-actin bundles. Moreover, these cells had increased glucose uptake and glycolysis, a phenotype disrupted by pharmacological perturbation of ROCK. However, glycolysis was unaffected by disruption of F-actin bundles, indicating that glycolytic stimulation in MAPKi-resistant melanoma is independent of F-actin organization. Instead, our findings highlight a mechanism in which elevated RhoA signaling activates ROCK, leading to the activation of insulin receptor substrate 1 (IRS1) and P85 of the PI3K pathway, which promotes cell surface expression of GLUT1 and elevated glucose uptake. Application of ROCK inhibitor GSK269962A results in reduced glucose uptake and glycolysis, thus impeding cell proliferation. Our study adds a mechanism to the proposed use of ROCK inhibitors for long-term treatments on MAPKi-resistant melanomas.
The role of locus coeruleus neuroimmune signaling in the response to social stress in female rats

Neuropsychiatric disorders that result from stress exposure, including post-traumatic stress disorder and substance abuse, are highly associated with central inflammation. Our previous work established that females selectively exhibit increased proinflammatory cytokine release within the noradrenergic locus coeruleus (LC) in response to witnessing social stress, which was associated with a hypervigilant phenotype. Thus, neuroimmune activation in the LC may be responsible for the heightened risk of developing mental health disorders following stress in females. Further, ablation of microglia using pharmacological techniques reduces the hypervigilant behavioral response exhibited by females during social stress. Therefore, these studies were designed to further investigate the impact of stress-induced neuroimmune signaling on the long-term behavioral and neuronal consequences of social stress exposure in females using DREADDs. We first characterized the use of an AAV-CD68-Gi-DREADD virus targeted to microglia within the LC. While the use of AAVs in preclinical research has been limited by observations regarding poor transfection efficiency in mice, recent data suggest that species specific differences in microglial genetics may render rats more receptive to chemogenetic targeting of microglia using a CD68 promoter. Therefore, clozapine-n-oxide (CNO) was used to activate the microglial expressed hM4Di to inhibit microglial activity during acute exposure to vicarious social defeat (witness stress, WS) in female rats. Neuroimmune activity within the LC, quantified by microglial morphology and cytokine release, was augmented by WS and prevented by chemogenetic microglial inhibition. Following confirmation of DREADD selectivity and efficacy, we utilized this technique to inhibit microglial activity during repeated WS. Subsequently, rats were tested in a marble burying paradigm and exposed to the WS cues and context to measure hypervigilant behaviors. Chemogenetic-mediated inhibition of microglial activity prior to each WS exposure prevented both acute and long-term hypervigilant responses induced by WS across multiple behavioral paradigms. Further, a history of microglial inactivation during WS prevented the heightened LC activity typically observed in response to stress cues. These studies are among the first to use a chemogenetic approach to inhibit microglia within the female brain in vivo and establish LC inflammation as a key mechanism underlying the behavioral and neuronal responses to social stress in females.
ER-detect: a pipeline for robust detection of early evoked responses in BIDS-iEEG electrical stimulation data

Human brain connectivity can be measured in different ways. Intracranial EEG (iEEG) measurements during single pulse electrical stimulation provide a unique way to assess the spread of electrical information with millisecond precision. To provide a robust workflow to process these cortico-cortical evoked potential (CCEP) data and detect early evoked responses in a fully automated and reproducible fashion, we developed Early Response (ER)-detect. ER-detect is an open-source Python package and Docker application to preprocess BIDS structured iEEG data and detect early evoked CCEP responses. ER-detect can use three response detection methods, which were validated against 14 manually annotated CCEP datasets from two different sites by four independent raters. Results showed that ER-detect’s automated detection performed on par with the inter-rater reliability (Cohen’s Kappa of ∼0.6). Moreover, ER-detect was optimized for processing large CCEP datasets, to be used in conjunction with other connectomic investigations. ER-detect provides a highly efficient standardized workflow such that iEEG-BIDS data can be processed in a consistent manner and enhance the reproducibility of CCEP based connectivity results.
An almost chromosome-level assembly and annotation of the Alectoris rufa genome

The red-legged partridge, Alectoris rufa (n=38 chromosomes) plays a crucial role in the ecosystem of southwestern Europe, and understanding its genetics is vital for conservation and management. Here we sequence, assemble, and annotate a highly contiguous and nearly complete version of it genome (115 scaffolds, L90=23). This assembly contains 96.9% (8078 out of 8332) orthologous genes from the BUSCO aves_odb10 dataset of single copy orthologous genes. We identify RNA and protein genes, 95% of which with functional annotation. This near-chromosome level assembly revealed significant chromosome rearrangements compared to quail (Coturnix japonica) and chicken (Gallus gallus), suggesting that A. rufa and C. japonica diverged 21 M-years ago and that their common ancestor diverged from G. gallus 37 M-years ago. The reported assembly is a significant step towards a complete reference genome for A. rufa, contributing to facilitate comparative avian genomics, and providing a valuable resource for future research and conservation efforts for the red-legged partridge.
Feedforward and disinhibitory circuits differentially control activity of cortical somatostatin-positive interneurons during behavioral state transitions

Local inhibitory neurons (INs), specifically those involved in disinhibitory circuits like somatostatin (SST) and vasoactive intestinal peptide (VIP)-positive INs, are essential for regulating cortical function during behavior. However, it is unclear the mechanisms by which these INs are recruited during active states and whether their activity is consistent across different sensory cortices. We now reveal that in mice, locomotor activity strongly recruits SST-INs in primary somatosensory (S1) but not visual (V1) cortex. This diverse engagement of SST-INs could not be explained by differences in VIP-IN function but was absent in the presence of visual sensory drive suggesting involvement of feedforward sensory pathways. In agreement, inactivating the somatosensory thalamus, but not decreasing VIP-INs activity, significantly reduces the recruitment of SST-INs in S1 by locomotion. Finally, model simulations suggest differences in SST-INs activity can be explained by varying ratios of VIP-driven inhibition and thalamus-driven cortical excitation. Our work suggests that by integrating feedforward activity with neuromodulation, SST-INs play a central role in adapting sensory processing to behavioral states.
Driver Maneuver Interaction Identification with Anomaly-Aware Federated Learning on Heterogeneous Feature Representations

Driver maneuver interaction learning (DMIL) refers to the classification task with the goal of identifying different driver-vehicle maneuver interactions (e.g., left/right turns). Existing conventional studies largely focused on the centralized collection of sensor data from the drivers' smartphones (say, inertial measurement units or IMUs, like accelerometer and gyroscope). Such a centralized mechanism might be precluded by data regulatory constraints. Furthermore, how to enable an adaptive and accurate DMIL framework remains challenging due to (i) complexity in heterogeneous driver maneuver patterns, and (ii) impacts of anomalous driver maneuvers due to, for instance, aggressive driving styles and behaviors. To overcome the above challenges, we propose AF-DMIL, an Anomaly-aware Federated Driver Maneuver Interaction Learning system. We focus on the real-world IMU sensor datasets (e.g., collected by smartphones) for our pilot case study. In particular, we have designed three heterogeneous representations for AF-DMIL regarding spectral, time series, and statistical features that are derived from the IMU sensor readings. We have designed a novel heterogeneous representation attention network (HetRANet) based on spectral channel attention, temporal sequence attention, and statistical feature learning mechanisms, jointly capturing and identifying the complex patterns within driver maneuver behaviors. Furthermore, we have designed a densely-connected convolutional neural network in HetRANet to enable the complex feature extraction and enhance the computational efficiency of HetRANet. In addition, we have designed within AF-DMIL a novel anomaly-aware federated learning approach for decentralized DMIL in response to anomalous maneuver data. To ease extraction of the maneuver patterns and evaluation of their mutual differences, we have designed an embedding projection network that projects the high-dimensional driver maneuver features into low-dimensional space, and further derives the exemplars that represent the driver maneuver patterns for mutual comparison. Then, AF-DMIL further leverages the mutual differences of the exemplars to identify those that exhibit anomalous patterns and deviate from others, and mitigates their impacts upon the federated DMIL. We have conducted extensive driver data analytics and experimental studies on three real-world datasets (one is harvested on our own) to evaluate the prototype of AF-DMIL, demonstrating AF-DMIL's accuracy and effectiveness compared to the state-of-the-art DMIL baselines (on average by more than 13% improvement in terms of DMIL accuracy), as well as fewer communication rounds (on average 29.20% fewer than existing distributed learning mechanisms).
The first small-bodied ornithopod dinosaur from the Lewisville Formation (middle Cenomanian) of Texas

ABSTRACT Sediments of the Woodbine Group exposed in northeastern Texas were deposited along the southwestern margin of Appalachia as a series of near-shore, shoreline, distal lowland swamp, lake, and fluvial deposits during a regression of the Western Interior Seaway in early and middle Cenomanian time. The Lewisville Formation (upper Woodbine Group) of north Texas preserves the most diverse terrestrial fossil assemblage known from Appalachia, but remains of small ornithischian dinosaurs have been conspicuously absent from it. An almost complete left dentary from the Lewisville Formation represents a new, small-bodied ornithopod taxon, Ampelognathus coheni gen. et sp. nov. The dentary is generally similar to those in non-iguanodontian ornithopods such as Hypsilophodon, Changchunsaurus, Haya, and Convolosaurus. Ampelognathus occupied an expected but previously missing component of the ‘mid’ Cretaceous terrestrial fauna of southwestern Appalachia. The growing diversity of fossil vertebrates and renewed paleobotanical study in the Lewisville Formation reinforces the importance of the unit’s fossil record for understanding eastern North American terrestrial ecosystems during an important transitional period in the earliest Late Cretaceous.http://zoobank.org/urn:lsid:zoobank.org:pub:02642649-ED6F-483A-994A-EC5F3FDF2AC7
Laser-Powered Vibrotactile Rendering

We investigate the feasibility of a vibrotactile device that is both battery-free and electronic-free. Our approach leverages lasers as a wireless power transfer and haptic control mechanism, which can drive small actuators commonly used in AR/VR and mobile applications with DC or AC signals. To validate the feasibility of our method, we developed a proof-of-concept prototype that includes low-cost eccentric rotating mass (ERM) motors and linear resonant actuators (LRAs) connected to photovoltaic (PV) cells. This prototype enabled us to capture laser energy from any distance across a room and analyze the impact of critical parameters on the effectiveness of our approach. Through a user study, testing 16 different vibration patterns rendered using either a single motor or two motors, we demonstrate the effectiveness of our approach in generating vibration patterns of comparable quality to a baseline, which rendered the patterns using a signal generator.