Miracle-dz/UniFAR-FTUs huggingface dataset:
River network scaling: Optimality and anisotropy

River networks are one of the many branching patterns in nature that exhibit power laws. The origin of these power laws is debated. Explanations of river network scaling have ranged from topological inevitability to growth mechanisms and from dynamics to optimality principles. The main contenders are dynamics and optimality, and the latter is controversial. The first part of my research is concerned with optimality theories of river networks. I distinguish between local and global optimality constraints. Under local constraints, optimality of an overall network is a byproduct of local optimality. Local optimality can be produced by dynamics, and is not controversial when this is the case. Under global constraints, optimality of an overall network is the result of direct optimization. Global constraint optimality is the truly controversial variety. I show that the success of global constraint theories is likely due to the optimization algorithm employed rather than to the optimality constraint itself. There exists a hierarchy of possible global constraints, some of which yield realistic river scaling while others do not, but no justification has been provided for why one constraint should be favored rather than another. Global constraint optimality lacks a mechanism and conflicts with erosion dynamics. Since these results indicate that optimality does not offer a satisfactory explanation of river network scaling, I turn to a degenerate network model, in which all steady-state networks have the same efficiency and thus questions of optimality are irrelevant. Simulations of this model show that scaling depends on initial conditions. Perturbations over time would also affect the scaling of this model. Based on these results, I argue that initial conditions and perturbations, together with dynamics, provide a more promising direction than optimality for understanding network scaling.
Determination of residue levels of rodenticide in rodent livers offered novel diphacinone baits by liquid chromatography-tandem mass spectrometry

A specific and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of the anticoagulant rodenticide diphacinone (DPN) in mouse and rat liver. Tissue samples were extracted with a mixture of water and acetonitrile containing ammonium hydroxide. The extracted sample was cleaned up with a combination of liquid-liquid partitioning and dispersive solid phase extraction. Chromatographic separation was achieved using a Waters X-Bridge BEH C-18 LC column (50 mm, 2.1 mm ID, 2.5 μm particle size) with detection on a triple quadrupole mass spectrometer in multiple reaction monitoring (MRM) mode. The monitored transition for DPN was m/z 339.0 → 167.0 for quantitation and 339.0 → 172.0 and 339.0 → 116.0 for confirmation. The linear range was 0.5 to 375 ng/mL. The average precision of DPN, represented by the relative standard deviation of the observed concentrations, was 7.2% (range = 0.97% - 20.4%) and the average accuracy, represented by the relative error, was 5.8% (range = 1.06% - 14.7%). The recovery of DPN fortified at 3 different levels averaged 106% in rat liver and 101% in mouse liver. The established method was successfully used to determine DPN residue levels in Polynesian rats (Rattus exulans) and mice (Mus musculus) fed two different formulated baits containing DPN. The observed residue levels were consistent with values observed in other rodent studies. However, the amount of bait consumed was lower for the novel baits evaluated in this study.
The Puzzle of Evaluating Moral Cognition in Artificial Agents

In developing artificial intelligence (AI), researchers often benchmark against human performance as a measure of progress. Is this kind of comparison possible for moral cognition? Given that human moral judgment often hinges on intangible properties like "intention" which may have no natural analog in artificial agents, it may prove difficult to design a "like-for-like" comparison between the moral behavior of artificial and human agents. What would a measure of moral behavior for both humans and AI look like? We unravel the complexity of this question by discussing examples within reinforcement learning and generative AI, and we examine how the puzzle of evaluating artificial agents' moral cognition remains open for further investigation within cognitive science.
Clinical significance of end of induction measurable residual disease monitoring in B‐cell acute lymphoblastic leukemia: A single center experience

The assessment of measurable residual disease (MRD) has emerged as a powerful prognostic tool for both pediatric and adult acute lymphoblastic leukemia (ALL). This retrospective study aimed to evaluate the prognostic relevance of the end of induction MRD in B‐cell acute lymphoblastic leukemia (B ALL) patients. The study included 481 patients who underwent treatment for B ALL between August 2012 and March 2019 and had their MRD at the end of induction assessed by flow cytometry. Baseline demographic characteristics were collected from the patient's clinical records. Event free survival (EFS) and relapse free survival (RFS) were calculated using Kaplan–Meier analysis and survival estimates were compared using the log‐rank test. End of induction MRD and baseline karyotype were the strongest predictors of EFS and RFS on multivariate analysis. The EFS was inversely related to the MRD value and the outcomes were similar in patients without morphological remission at the end of induction and patients in remission with MRD ≥1.0%. Even within the subgroups of ALL based on age, karyotype, BCR::ABL1 translocation and the treatment protocol, end of induction MRD positive patients had poor outcomes compared to patients who were MRD negative. The study outcome would help draft end of induction MRD‐based treatment guidelines for the management of B ALL patients.
Environmental Flow Assessment of the Lower Coal River and Pitt Water Estuary

This report describes a project designed to derive an environmental flow regime for the lower Coal River, southern Tasmania, downstream of Craigbourne Dam, and its estuary and related coastal embayment, Pitt Water. Within the current Tasmanian water management policy context, the principle aim of an environmental flow regime is to maintain existing values. This implies a focus on existing conditions. However, opportunities for environmental rehabilitation/ restoration should also be explored where they are broadly commensurate with the existing water management focus, which in the lower Coal is on irrigation water supply. The Coal catchment has been extensively cleared for grazing, and development for intensive agriculture has been stimulated by the development of irrigation infrastructure. This development has had a number of consequences for the Coal River and Pitt Water, whose environmental condition is discussed in Sections 2-4 of this report.
Coupled sodium channels: Does it really take two to tango?

Voltage-gated sodium channels (NaV1.1-1.9) are physiologically essential as they support the rapid upstroke and brisk spatial propagation of action potentials in the heart, skeletal muscle and neurons (Ahern et al., 2016). Alterations in NaV function underlies a wide range of severe and life-threatening clinical phenotypes, including cardiac arrhythmias, myotonia, periodic paralysis, epilepsy and pain disorders. As such, elucidating fundamental mechanisms that govern channel function is crucial for an in depth understanding of pathophysiology and for developing targeted therapies. At the molecular level, NaV channels are multisubunit complexes composed of a pore-forming α-subunit, one or more transmembrane β subunits, and a bevy of interacting proteins that fine-tune channel function and localization (Ahern et al., 2016). Furthermore, the α-subunit has a distinctive pseudo-tetrameric arrangement composed of four voltage-sensing domains and a central ion permeation pathway. At hyperpolarized potentials, the ion conduction pathway is closed. Upon depolarization, movement of various voltage-sensing domains couple to activation gates that open the channel, thereby permitting influx of Na+ ions into the cell. Subsequently, movement of an intracellular blocking particle occludes the pore and prevents channel openings, a process known as channel inactivation. The textbook view has been that each channel, stochastic in nature, operates independently without regard to the status of its neighbour (Fig. 1). Recent studies have cast doubt on this paradigm. First, in the physiological setting, NaV channels are often clustered at specific subcellular locations as previously reviewed (Eshed-Eisenbach & Peles, 2021). In cardiomyocytes, large clusters of NaV1.5 channels are found at the intercalated disc, specialized cell–cell junctions that connect cardiomyocytes. Similarly, clusters of neuronal NaV channels can be found at the axon initiation segment and at nodes of Ranvier in myelinated neurons. Second, both cross-linking experiments and single molecule photobleaching experiments of NaV1.5 expressed in heterologous systems support the notion that channels may assemble as dimers and not as monomers (Clatot et al., 2017). Third, single channel experiments showed that dimeric channels simultaneously open and close, as though they are biophysically or conformationally coupled (Clatot et al., 2017). Taken together, these experiments suggested that the elementary functional unit of NaV channels is not a monomer but, instead, a dimer that undergoes cooperative gating (Fig. 1). Channel dimerization was proposed to be mediated by the dimeric 14-3-3 protein that binds the channel in a phosphorylation-dependent manner. This
Big ideas series: self-regulation shift theory: trauma, suicide, and violence

ABSTRACT Background Traumatic stress, suicide, and impulsive violence arguably are three of the most consequential problems facing societies today. Self-regulation shift theory is introduced to capture the underlying coping dynamics involved in these three grave challenges. Objectives Self-regulation shift theory, based in a nonlinear dynamical systems framework, focuses on critical psychological self-regulation thresholds and the role of cognitive self-appraisals in human adaptation to help understand these three significant societal challenges. Methods This essay reviews existing evidence within the posttraumatic adaptation process utilizing SRST for understanding dynamic self-regulation. This is followed by integrating SRST within existing current theoretical models for suicidal behaviors and violent outbursts. Conclusions The essay concludes with methodological suggestions for future research applying SRST and how this research offers important opportunities to develop early warning systems that promote hope when hope seems impossible.
Linking the Mechanics of Chewing to Biology of the Junctional Epithelium

The capacity of a tissue to continuously alter its phenotype lies at the heart of how an animal is able to quickly adapt to changes in environmental stimuli. Within tissues, differentiated cells are rigid and play a limited role in adapting to new environments; however, differentiated cells are replenished by stem cells that are defined by their phenotypic plasticity. Here we demonstrate that a Wnt-responsive stem cell niche in the junctional epithelium is responsible for the capability of this tissue to quickly adapt to changes in the physical consistency of a diet. Mechanical input from chewing is required to both establish and maintain this niche. Since the junctional epithelium directly attaches to the tooth surface via hemidesmosomes, a soft diet requires minimal mastication, and consequently, lower distortional strains are produced in the tissue. This reduced strain state is accompanied by reduced mitotic activity in both stem cells and their progeny, leading to tissue atrophy. The atrophied junctional epithelium exhibits suboptimal barrier functions, allowing the ingression of bacteria into the underlying connective tissues, which in turn trigger inflammation and mild alveolar bone loss. These data link the mechanics of chewing to the biology of tooth-supporting tissues, revealing how a stem cell niche is responsible for the remarkable adaptability of the junctional epithelium to different diets.
α4-Containing GABAA Receptors on DRD2 Neurons of the Nucleus Accumbens Mediate Instrumental Responding for Conditioned Reinforcers and Its Potentiation by Cocaine

Abstract Extrasynaptic GABAA receptors (GABAARs) composed of α4, β, and δ subunits mediate GABAergic tonic inhibition and are potential molecular targets in the modulation of behavioral responses to natural and drug rewards. These GABAARs are highly expressed within the nucleus accumbens (NAc), where they influence the excitability of the medium spiny neurons. Here, we explore their role in modulating behavioral responses to food-conditioned cues and the behavior-potentiating effects of cocaine. α4-Subunit constitutive knock-out mice (α4−/−) showed higher rates of instrumental responding for reward-paired stimuli in a test of conditioned reinforcement (CRf). A similar effect was seen following viral knockdown of GABAAR α4 subunits within the NAc. Local infusion of the α4βδ-GABAAR-preferring agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; Gaboxadol) into the NAc had no effect on responding when given alone but reduced cocaine potentiation of responding for conditioned reinforcers in wild-type, but not α4−/− mice. Finally, specific deletion of α4-subunits from dopamine D2, but not D1, receptor-expressing neurons (DRD2 and DRD1 neurons), mimicked the phenotype of the constitutive knockout, potentiating CRf responding, and blocking intra-accumbal THIP attenuation of cocaine-potentiated CRf responding. These data demonstrate that α4-GABAAR-mediated inhibition of DRD2 neurons reduces instrumental responding for a conditioned reinforcer and its potentiation by cocaine and emphasize the importance of GABAergic signaling within the NAc in mediating the effects of cocaine.
Inheritance and fitness cost of laboratory-selected resistance to Vip3Aa in Helicoverpa zea (Lepidoptera: Noctuidae)

The polyphagous pest Helicoverpa zea (Lepidoptera: Noctuidae) has evolved practical resistance to transgenic corn and cotton producing Cry1 and Cry2 crystal proteins from Bacillus thuringiensis (Bt) in several regions of the United States. However, the Bt vegetative insecticidal protein Vip3Aa produced by Bt corn and cotton remains effective against this pest. To advance knowledge of resistance to Vip3Aa, we selected a strain of H. zea for resistance to Vip3Aa in the laboratory. After 28 generations of continuous selection, the resistance ratio was 267 for the selected strain (GA-R3) relative to a strain not selected with Vip3Aa (GA). Resistance was autosomal and almost completely recessive at a concentration killing all individuals from GA. Declines in resistance in heterogeneous strains containing a mixture of susceptible and resistant individuals reared in the absence of Vip3Aa indicate a fitness cost was associated with resistance. Previously reported cases of laboratory-selected resistance to Vip3Aa in lepidopteran pests often show partially or completely recessive resistance at high concentrations and fitness costs. Abundant refuges of non-Bt host plants can maximize the benefits of such costs for sustaining the efficacy of Vip3Aa against target pests.
Mitochondrial metabolites predict adverse cardiovascular events in individuals with diabetes

Metabolic mechanisms underlying the heterogeneity of major adverse cardiovascular (CV) event (MACE) risk in individuals with type 2 diabetes mellitus (T2D) remain unclear. We hypothesized that circulating metabolites reflecting mitochondrial dysfunction predict incident MACE in T2D. Targeted mass-spectrometry profiling of 60 metabolites was performed on baseline plasma samples from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS; discovery cohort) and Exenatide Study of Cardiovascular Event Lowering (EXSCEL; validation cohort) biomarker substudy cohorts. A principal components analysis metabolite factor comprising medium-chain acylcarnitines (MCACs) was associated with MACE in TECOS and validated in EXSCEL, with higher levels associated with higher MACE risk. Meta-analysis showed that long-chain acylcarnitines (LCACs) and dicarboxylacylcarnitines were also associated with MACE. Metabolites remained associated with MACE in multivariate models and favorably changed with exenatide therapy. A third cohort (Cardiac Catheterization Genetics [CATHGEN]) with T2D was assessed to determine whether these metabolites improved discriminative capability of multivariate models for MACE. Nine metabolites (MCACs and LCACs and 1 dicarboxylacylcarnitine) were associated with time to MACE in the CATHGEN cohort. Addition of these metabolites to clinical models minimally improved the discriminative capability for MACE but did significantly down reclassify risk. Thus, metabolites reporting on dysregulated mitochondrial fatty acid oxidation are present in higher levels in individuals with T2D who experience subsequent MACE. These biomarkers may improve CV risk prediction models, be therapy responsive, and highlight emerging risk mechanisms.
Association of Leukocyte Subpopulations Identified by Flow Cytometry with Outcomes of Sepsis in a Respiratory Intensive Care Unit: An Observational Study

Introduction The dysregulated host immune response in sepsis is orchestrated by peripheral blood leukocytes. This study explored the associations of the peripheral blood leukocyte subpopulations with early clinical deterioration and mortality in sepsis. Methods We performed a prospective observational single-center study enrolling adult subjects with sepsis within 48 h of hospital admission. Peripheral blood flow cytometry was performed for the patients at enrolment and after 5 days. The primary outcome was to explore the association between various leukocyte subpopulations at enrolment and early clinical deterioration [defined as an increase in the sequential organ failure assessment (SOFA) score between enrolment and day 5, or death before day 5]. Other pre-specified outcomes explored associations of leukocyte subpopulations at enrolment and on day 5 with in-hospital mortality. Results A total of 100 patients, including 47 with septic shock were enrolled. The mean (SD) age of the patients was 53.99 (14.93) years. Among them, 26 patients had early clinical deterioration, whereas 41 died during hospitalization. There was no significant association between the leukocyte subpopulations at enrolment and early clinical deterioration on day 5. On multivariate logistic regression, a reduced percentage of CD8 + CD25+ T-cells at enrolment was associated with in-hospital mortality [odds ratio (OR), 0.82 (0.70-0.97); p-value = 0.02]. A reduced lymphocyte percentage on day 5 was associated with in-hospital mortality [OR, 0.28 (0.11-0.69); p-value = 0.01]. In a post-hoc analysis, patients with “very early” deterioration within 48 h had an increased granulocyte CD64 median fluorescent intensity (MFI) [OR, 1.07 (1.01-1.14); p-value = 0.02] and a reduced granulocyte CD16 MFI [OR, 0.97 (0.95-1.00); p-value = 0.04] at enrolment. Conclusions None of the leukocyte subpopulations showed an association with early clinical deterioration at day 5. Impaired lymphocyte activation and lymphocytopenia indicative of adaptive immune dysfunction may be associated with in-hospital mortality.
The Evolution, Assembly, and Dynamics of Marine Holobionts.

The holobiont concept (i.e., multiple living beings in close symbiosis with one another and functioning as a unit) is revolutionizing our understanding of biology, especially in marine systems. The earliest marine holobiont was likely a syntrophic partnership of at least two prokaryotic members. Since then, symbiosis has enabled marine organisms to conquer all ocean habitats through the formation of holobionts with a wide spectrum of complexities. However, most scientific inquiries have focused on isolated organisms and their adaptations to specific environments. In this review, we attempt to illustrate why a holobiont perspective-specifically, the study of how numerous organisms form a discrete ecological unit through symbiosis-will be a more impactful strategy to advance our understanding of the ecology and evolution of marine life. We argue that this approach is instrumental in addressing the threats to marine biodiversity posed by the current global environmental crisis. Expected final online publication date for the Annual Review of Marine Science, Volume 16 is January 2024. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Change detection versus change localization for faces, houses, and words

Holistic processing aids in the discrimination of visually similar objects, but it may also come with a cost. Indeed holistic processing may improve the ability to detect changes to a face while impairing the ability to locate where the changes occur. We investigated the capacity to detect the occurrence of a change versus the capacity to detect the localization of a change for faces, houses, and words. Change detection was better than change localization for faces. Change localization outperformed change detection for houses. For words, there was no difference between detection and localization. We know from previous studies that words are processed holistically. However, being an object of visual expertise processed holistically, visual words are also a linguistic entity. Previously, the word composite effect was found for phonologically consistent words but not for phonologically inconsistent words. Being an object of visual expertise for which linguistic information is important, letter position information, is also crucial. Thus, the importance of localization of letters and features may augment the capacity to localize a change in words making the detection of a change and the detection of localization of a change equivalent.
Medium Term Educational Consequences of Alternative Conditional Cash Transfer Designs: Experimental Evidence from Colombia

We show that three Colombian conditional cash transfer (CCT) programs for secondary school improve educational outcomes after eight years, depending on the stipend structure. Forcing families to save a portion of the transfers until they make enrollment decisions for the next year increases on-time enrollment in secondary school, reduces dropout rates, and promotes tertiary enrollment. Traditional stipends improve on-time enrollment and high school exit exam completion rates. These differences between stipends are statistically significant due to the effects on older students. Finally, a stipend that directly incentivizes tertiary enrollment promotes on-time enrollment in secondary school and in lower quality tertiary institutions.
Digesters as heat storage: Effects of the digester temperature on the process stability, sludge liquor quality, and the dewaterability

Variation of the digester temperature during the year enables the operation of digesters as seasonal heat storage contributing to a holistic heat management at water resource recovery facilities. Full‐ and lab‐scale process data were conducted to examine the effect of the digester temperature on process stability, sludge liquor quality, and dewaterability. Both full‐ and lab‐scale digesters show a stable anaerobic degradation process with a hydraulic retention time of more than 20 days and organic load rates up to 2.2‐kg COD/(m3·day) at temperatures between 33 and 53°C. The concentrations of soluble COD and ammonium‐nitrogen in the sludge liquor digested at 53°C are 2.6 to 5.8 times and 1.3 times higher, respectively, than in the sludge liquor digested at 37°C. Dewatering tests show an enhancement of the dewaterability but a clear increase in the polymer demand at increased digester temperature.