Miracle-dz/UniFAR-FTUs huggingface dataset:
Constraining cooling histories: rutile and titanite chronology and diffusion modelling in NW Bhutan

U–Pb analyses of rutile and titanite commonly yield ages that constrain the timing of cooling rather than the timing of their crystallization. Rutile which grew at or close to peak temperature conditions in a mafic granulite, intermediate granulite and mafic amphibolite within juxtaposed litho/tectonostratigraphic units in the Greater Himalayan Sequence (GHS) of NW Bhutan yield LA–MC–ICP–MS U–Pb lower intercept cooling ages of 10.1 ± 0.4, 10.8 ± 0.1 and 10.0 ± 0.3 Ma, respectively. Numerical finite‐difference diffusion models constrained by previously published temperature–time and Pb diffusion data suggest that these ages are best explained by rapid cooling from peak temperature conditions of ∼800 °C at 14 Ma in the granulite‐bearing unit and ∼650 °C at 12 Ma in the amphibolite‐bearing unit. The good fit between the model and analysed ages confirms the relatively high retention of Pb in rutile suggested by the experimental data. Titanite that grew during an exhumation‐related amphibolite facies overprint on an eclogite facies mineral assemblage from the neighbouring Jomolhari Massif yields a U–Pb lower intercept cooling age of 14.6 ± 1.2 Ma. Diffusion modelling suggests that this age is too old to be consistent with the temperature–time paths inferred for the rutile‐bearing samples. Instead, the titanite age suggests cooling from ∼650 °C at an earlier time of 17–15 Ma, implying that the high‐grade rocks in the Jomolhari Massif experienced a different cooling history from the rest of the GHS in NW Bhutan. Together these data show that high‐grade rocks from three apparently different structural levels of the GHS in NW Bhutan experienced rapid cooling at >40 °C Ma−1 at varying times. The highest grade granulite facies rocks were exhumed from deeper structural levels that are not exposed, not preserved, or not yet recognized west of eastern Nepal. A progressive along‐strike change in tectonic regime, metamorphic history and/or exhumation mechanism across the orogen is implied by these thermochronologic data.
‘Money looks for money’: managing financialization in eastern Uganda

Abstract Savings groups are an important feature of life in rural Uganda and elsewhere. They have been celebrated as an ‘alternative’, community-based approach to economic development with a particular focus on empowering women. In this article we offer a more critical perspective, showing how a savings group in a village in eastern Uganda informs more general experiences of financialization. Joining the group was not really an ‘alternative’ to other forms of finance and was often a first step to securing loans from moneylenders, microfinance institutions and commercial banks. We show how poorer members of the group, typically women, ‘rented out’ their membership to wealthier villagers. Members also used the Friday meetings to socialize and to build political careers, and to reflect critically on experiences of financialization. ‘Money looks for money’, a phrase new to the area, interrogates these socialities and inequalities, as part of the seemingly inexorable pull of loans, interest and financialized debt.
A high-resolution nonmarine record of an early Danian hyperthermal event, Boltysh crater, Ukraine

Carbon isotope and palynological analysis of the fine-grained organic carbon–rich lacustrine sediments that filled the Cretaceous-Paleogene (K-Pg) boundary–age Boltysh impact crater (Ukraine) preserve a uniquely complete and detailed record of a negative carbon isotope excursion in an expanded section of the early Danian that we estimate lasted as long as ∼340 k.y. Palynological assemblages recovered through the excursion reflect the increasing dominance of thermophylic Normapolles species, indicating an increasingly warm and dry climate, while those recovered below and above the excursion reflect a cooler and wetter climate. The record of a transient warming event (hyperthermal) in the early Danian at Boltysh has strong similarities with the Dan-C2 hyperthermal event recorded in marine sediments in Tethys and the Atlantic Ocean, and suggests that there were profound environmental changes occurring on a global scale shortly after the K-Pg boundary.
Evolution of surface ozone in central Italy based on observations and statistical model

[1] Hourly and daily variations of surface ozone have been analyzed in relation to radon and meteorological parameters to explore its controlling mechanisms. Measurements in central Italy cover the years 2004 and 2005, showing a relevant role of transport in the ozone concentration variability. An analysis based on back trajectories shows that the site is affected by air masses originating from the west to northeast sector in about 74% of the days, suggesting that L’Aquila could be considered a background site. The background hypothesis is also supported by the rather low values of the following ozone quantities: maximum of monthly averages (39 ppbv, July), annual median of hourly data (29 ppbv), and annual average of hourly maxima recorded daily (49 ppbv). Only six hourly data recorded ozone above 90 ppbv in 2 years but never above 100 ppbv. The regression model reproduces measured ozone with accuracy in 67% of hourly observations and 74% of daily mean data. Here the model includes information from the following meteorological parameters: temperature, relative humidity, horizontal wind speed/direction, sun radiation, and radon concentration. A tracer like radon that tracks the dynamical changes of the lower atmosphere has a significant role in the model ozone prediction improvement, especially for hourly observations and for the synoptic component. In the first case (hourly observation), inclusion of radon data improves the regression model performance by 5% (from 62 to 67%); in the last case (synoptic component), the model accuracy increases by 3% (from 78 to 81%).
Flower structures and Riedel shears at a step over zone along the Alpine Fault (New Zealand) inferred from 2-D and 3-D GPR images

[1] High-resolution GPS and ground-penetrating radar (GPR) data are used to detect and identify hidden faults along a stretch of the transpressional Alpine Fault (South Island, New Zealand) immediately north of its junction with the Hope Fault. At this location, the Alpine Fault emerges from the basement into a sequence of variably thick late Holocene gravel deposits. Geomorphology and trenching already mapped three principal fault strands and two distinct step over zones at the study site. Our GPR images reveal numerous additional secondary fault strands throughout the region, only some of which are obvious at the surface or in the trench walls. According to the GPR data, the main fault-generated disturbance zone has a width ranging from ∼40 to ∼200 m. The secondary fault strands outside of the step over zones likely represent the branches of positive flower structures, whereas the faulting pattern around the step over zones is best explained in terms of linked Riedel shears. Systematic northeastward increases in the width of the main fault-generated disturbance zone and corresponding increases in principal fault-scarp height are the likely consequences of older terraces in the northeast being disrupted and offset by more earthquakes than younger terraces in the southwest. The pattern of complex faulting in this region is distinct from the system of alternating strike-slip and reverse faults characteristic of the Alpine Fault to the south and from the rather simple sequence of faults mapped to the north. GPR surveying has added new information on the distribution and nature of faulting at our study site.
An NVM Performance Study Towards Whole System Persistence on Server Platforms

Whole system persistence (WSP) is a concept for retaining the computational state of a system even in case of a power failure. In the context of server systems, WSP could render it possible to quickly power on and off machines that only need to be used occasionally, thus saving energy. This paper takes on this idea and discusses multiple approaches for implementing WSP on such machines. Our evaluation shows that after starting a system, an NVM-based version of WSP can achieve tail latency improvements of up to 93% compared to booting a system and loading data from an SSD. At the same time, WSP is able to provide suspend and resume times in the order of tens of milliseconds.
Typical solutions of the differential equations of statistical theories of flow through porous media

The description of the miscible displacement process in porous media (such as occurs, for example, during the pollution of ground-water resources with wastes) by methods of statistical mechanics has met with considerable success. The method usually employed is that of considering the motion of each particle through the medium as a random-walk process. Recently, however, it has been suggested that autocorrelation should also be taken into account and a differential equation allowing for this effect to take place has been arrived at. The purpose of the present paper is to give solutions of the autocorrelation equation for some typical cases and to compare the result with that obtained for the random walk model without autocorrelation. These cases refer to the passage of a thin slug of ‘tagged’ fluid through a porous medium and to the intrusion of a sharp concentration front into a medium. It is shown that autocorrelation has the effect that a concentration-discontinuity proceeds at a finite speed into the medium which cuts off the infinite ‘tail’ of the solution without autocorrelation. Graphs to illustrate the situation are given.
Physically stressed bees expect less reward in an active choice judgement bias test

Emotion-like states in animals are commonly assessed using judgment bias tests, which measure responses to ambiguous information. A few studies have recently used these tests to argue for the presence of emotion-like states in insects. However, the results from most of these studies could have other explanations, including changes in motivation and attention. To control for these explanations, we therefore developed a novel judgment bias test, requiring bumblebees to make an active choice indicating their interpretation of ambiguous stimuli. Bumblebees were trained to associate high or low rewards, delivered in two different reward chambers, with distinct colors. Two groups of bees were then physically stressed by shaking or trapping, while the third group served as a control. We subsequently presented the bees with ambiguous colors between the two learnt colors and noted which reward chamber they chose. When presented with ambiguous colors, stressed bees were less likely than control bees to enter the reward chamber previously associated with high reward. We modelled bee behavior using signal detection and drift diffusion models and showed that control bees and stressed bees were, respectively, more likely to respond optimistically and pessimistically to ambiguous cues. The signal detection model further showed that the behavior of stressed bees was explained by a reduction in their prior expectation of high rewards. Our findings thus provide strong evidence for emotion-like states in bees and suggest that their stress-induced pessimistic behavior is explained by a reduced expectation of higher rewards.
Microglia shape hippocampal networks but are dispensable for pruning of synapses during development

Microglia, the brain-resident macrophages, are believed to sculpt developing neural circuits by eliminating excess synapses in a process called synaptic pruning, removing apoptotic neurons, and promoting neuronal survival. To elucidate the role of microglia during embryonic and postnatal brain development, we used a mouse model deficient in microglia throughout life as a consequence of deletion of the fms-intronic regulatory element (FIRE) in the Csf1r locus. Surprisingly, young adult Csf1rΔFIRE/ΔFIRE mice displayed no changes in excitatory synapse number and spine density of CA1 hippocampal neurons compared to Csf1r+/+ littermates. However, CA1 neurons were less excitable, received less CA3 Schaffer collateral-mediated excitatory input and showed altered synaptic properties, but this did not affect novel object recognition. Cytokine profiling indicated an anti-inflammatory state along with increases in ApoE levels and astrocyte reactivity in brains of Csf1rΔFIRE/ΔFIRE mice. Notably, these morphological and functional changes in Csf1rΔFIRE/ΔFIRE mice closely resemble the effects of acute microglial depletion in adult mice that had undergone normal development. Thus, our findings challenge the prevailing view that microglia are indispensable for the establishment of neural networks during development.
Convective quasi‐equilibrium

The concept of convective quasi‐equilibrium (CQE) is a key ingredient in order to understand the role of deep moist convection in the atmosphere. It has been used as a guiding principle to develop almost all convective parameterizations and provides a basic theoretical framework for large‐scale tropical dynamics. The CQE concept as originally proposed by Arakawa and Schubert (1974) is systematically reviewed from wider perspectives. Various interpretations and extensions of Arakawa and Schubert's CQE are considered both in terms of a thermodynamic analogy and as a dynamical balance. The thermodynamic interpretations can be more emphatically embraced as a homeostasis. The dynamic balance interpretations can be best understood by analogy with the slow manifold. Various criticisms of CQE can be avoided by taking the dynamic balance interpretation. Possible limits of CQE are also discussed, including the importance of triggering in many convective situations, as well as the possible self‐organized criticality of tropical convection. However, the most intriguing aspect of the CQE concept is that in spite of many observational tests supporting and interpreting it in many different senses, it has never been established in a robust manner based on a systematic analysis of the cloud work function budget by observations as was originally defined.
Drug Discovery in Low Data Regimes: Leveraging a Computational Pipeline for the Discovery of Novel SARS-CoV-2 Nsp14-MTase Inhibitors

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant global morbidity and mortality. A crucial viral protein, the non-structural protein 14 (nsp14), catalyzes the methylation of viral RNA and plays a critical role in viral genome replication and transcription. Due to the low mutation rate in the nsp region among various SARS-CoV-2 variants, nsp14 has emerged as a promising therapeutic target. However, discovering potential inhibitors remains a challenge. In this work, we introduce a computational pipeline for the rapid and efficient identification of potential nsp14 inhibitors by leveraging virtual screening and the NCI open compound collection, which contains 250,000 freely available molecules for researchers worldwide. The introduced pipeline provides a cost-effective and efficient approach for early-stage drug discovery by allowing researchers to evaluate promising molecules without incurring synthesis expenses. Our pipeline successfully identified seven promising candidates after experimentally validating only 40 compounds. Notably, we discovered NSC620333, a compound that exhibits a strong binding affinity to nsp14 with a dissociation constant of 427 ± 84 nM. In addition, we gained new insights into the structure and function of this protein through molecular dynamics simulations. We identified new conformational states of the protein and determined that residues Phe367, Tyr368, and Gln354 within the binding pocket serve as stabilizing residues for novel ligand interactions. We also found that metal coordination complexes are crucial for the overall function of the binding pocket. Lastly, we present the solved crystal structure of the nsp14-MTase complexed with SS148 (PDB:8BWU), a potent inhibitor of methyltransferase activity at the nanomolar level (IC50 value of 70 ± 6 nM). Our computational pipeline accurately predicted the binding pose of SS148, demonstrating its effectiveness and potential in accelerating drug discovery efforts against SARS-CoV-2 and other emerging viruses.
Hypoxic injury triggers maladaptive repair in human kidney organoids

Acute kidney injury (AKI) is a common clinical disorder linked to high rates of illness and death. Ischemia is a leading cause of AKI, which can result in chronic kidney disease (CKD) through a maladaptive repair process characterised by failed epithelial regeneration, inflammation, and metabolic dysregulation. No targeted therapies exist to prevent the AKI to CKD transition and insight into ischemic AKI and maladaptive repair in humans remains limited. In this study, we report that human kidney organoids recapitulate select molecular and metabolic signatures of AKI and maladaptive repair in response to hypoxic injury. Transcriptional, proteomic, and metabolomic profiling revealed signatures of tubular injury, cell death, cell cycle arrest and altered metabolism in kidney organoids cultured in hypoxic conditions. After recovery in normoxic conditions, injured organoids displayed increased signatures associated with maladaptive repair like TNF, NF-κB, and JAK-STAT pathways, and S100A8/9. Single cell RNA sequencing localised biomarkers of AKI and maladaptive repair such as GDF15, MMP7, ICAM1, TGFB1, SPP1, C3 and CCN1 to injured proximal and distal tubules. Metabolic phenotypes linked to CKD were also evident including dysregulated glycolysis and gluconeogenesis, amino acid, bicarbonate and lipid metabolism, and elevated ceramide levels. Our multi-omic analysis provides compelling evidence for the use of kidney organoids as a model of human ischemic AKI and maladaptive repair, highlighting new and conserved biomarkers and mechanisms, and opportunities for drug screening. Summary Human kidney organoids recapitulate molecular and metabolic signatures of ischemic acute kidney injury and maladaptive repair, providing new insight into human disease mechanisms and opportunities for drug development.
Rewiring native post-transcriptional carbon regulators to build multi-layered genetic circuits and optimize engineered microbes for bioproduction

As the bioprocessing and synthetic biology spaces rapidly expand, post-transcriptional regulation is emerging as driver for maximizing signal response rate and for minimizing cost per protein within cells. Designing robust post-transcriptional control systems that have precise tunability and can achieve diverse regulatory outcomes are paramount to advance the field. Herein, we develop a new approach for engineered post-transcriptional control in bacteria by rewiring a native regulatory system in Escherichia coli, the Carbon Storage Regulatory (Csr) Network, to create tunable, complex genetic circuits. First, by co-opting native components of the Csr Network to regulate translation of a target mRNA transcript, we establish a Csr-regulated Buffer Gate. Next, by rationally engineering the interactions between our synthetic construct and the native components of the Csr Network, we expand our original design into a genetic toolbox of 12 Buffer Gates that achieve precise tunability across a 10-fold range of target gene expression. Subsequently, to further regulatory capabilities using this approach, we develop a Csr-regulated NOT Gate through engineering a Csr-activated sequence into our synthetic constructs. We then build upon the Csr Buffer and Not Gates to create post-transcriptional dual input Boolean OR, NOR, AND and NAND Logic Gates, as well as a genetic pulse circuit. As a third step, we demonstrate portability of our Csr-regulated Buffer Gates into three industrially relevant bacteria by recapitulating Buffer Gate activity simply by leveraging the conserved homologous Csr Network in each species. Lastly, as a demonstration of downstream application, we apply our system to a proof-of-concept synthetic mevalonate pathway. Using our engineered constructs, we optimize mevalonate production in E. coli resulting in a three-fold increase in production relative to a transcriptionally controlled mevalonate pathway. As a whole, we establish a novel approach to rewire post-transcriptional regulatory networks for complex bacterial computation that can be utilized for efficient bioproduction in engineered microbes.
Voluntary alcohol consumption during distinct phases of adolescence differentially alters adult fear acquisition, extinction and renewal in male and female rats

Alcohol use during adolescence coincides with elevated risks of stress-related impairment in adults, particularly via disrupted developmental trajectories of vulnerable corticolimbic and mesolimbic systems involved in fear processing. Prior work has investigated the impact of binge-like alcohol consumption on adult fear and stress, but less is known about whether voluntarily consumed alcohol imparts differential effects based on adolescence phases and biological sex. Here, adolescent male and female Long Evans rats were granted daily access to alcohol (15%) during either early (Early-EtOH; P25-45) or late adolescence (Late-EtOH; P45-55) using a modified drinking-in-the-dark design. Upon adulthood (P75-80), rats were exposed to a three-context (ABC) fear renewal procedure. We found that male and female Early-EtOH rats showed faster acquisition of fear but less freezing during early phases of extinction and throughout fear renewal. In the extinction period specifically, Early-EtOH rats showed normal levels of freezing in the presence of fear-associated cues, but abnormally low freezing immediately after cue offset, suggesting a key disruption in contextual processing and/or novelty seeking brought by early adolescent binge consumption. While the effects of alcohol were most pronounced in the Early-EtOH rats (particularly in females), Late-EtOH rats displayed some changes in fear behavior including slower fear acquisition, faster extinction, and reduced renewal compared with controls, but primarily in males. Our results suggest that early adolescence in males and females and, to a lesser extent, late adolescence in males is a particularly vulnerable period wherein alcohol use can promote stress-related dysfunction in adulthood. Furthermore, our results provide multiple bases for future research focused on developmental correlates of alcohol mediated disruption in the brain.