Miracle-dz/UniFAR-FTUs huggingface dataset:
High postural costs and anaerobic metabolism during swimming support the hypothesis of a U-shaped metabolism–speed curve in fishes

Significance Hydrodynamic theory predicts that the energetic costs required for fishes to swim should vary with speed according to a U-shaped curve, with an expected energetic minimum at intermediate cruising speeds. Empirical studies to date do not support this view. Here we report a complete dataset on a swimming batoid fish that shows a clear energetic minimum at intermediate swimming speeds. We also demonstrate that this species uses a combination of aerobic and anaerobic metabolism to fuel steady swimming at each speed, including the slowest speeds tested. This contradicts the widespread assumption that fish use only aerobic metabolism at low speeds. Kinematic data support this nonlinear relationship by also showing a U-shaped pattern to body angle during steady swimming. Swimming performance is considered a key trait determining the ability of fish to survive. Hydrodynamic theory predicts that the energetic costs required for fishes to swim should vary with speed according to a U-shaped curve, with an expected energetic minimum at intermediate cruising speeds and increasing expenditure at low and high speeds. However, to date no complete datasets have shown an energetic minimum for swimming fish at intermediate speeds rather than low speeds. To address this knowledge gap, we used a negatively buoyant fish, the clearnose skate Raja eglanteria, and took two approaches: a classic critical swimming speed protocol and a single-speed exercise and recovery procedure. We found an anaerobic component at each velocity tested. The two approaches showed U-shaped, though significantly different, speed–metabolic relationships. These results suggest that (i) postural costs, especially at low speeds, may result in J- or U-shaped metabolism–speed curves; (ii) anaerobic metabolism is involved at all swimming speeds in the clearnose skate; and (iii) critical swimming protocols might misrepresent the true costs of locomotion across speeds, at least in negatively buoyant fish.
Underutilization of Statins When Indicated in HIV‐Seropositive and Seronegative Women

Abstract Increased life expectancy of persons living with HIV infection receiving antiretroviral therapy heightens the importance of preventing and treating chronic comorbidities such as cardiovascular disease. While guidelines have increasingly advocated more aggressive use of statins for low‐density lipoprotein (LDL) cholesterol reduction, it is unclear whether people with HIV, especially women, are receiving statins when indicated, and whether their HIV disease is a factor in access. We assessed the cumulative incidence of statin use after an indication in the Women's Interagency HIV Study (WIHS), from 2000 to 2014. Additionally, we used weighted proportional hazards regression to estimate the effect of HIV serostatus on the time to initiation of a statin after an indication. Cumulative incidence of statin use 5 years after an indication was low: 38% in HIV‐seropositive women and 30% in HIV‐seronegative women. Compared to HIV‐seronegative women, the weighted hazard ratio for initiation of a statin for HIV‐seropositive women over 5 years was 0.94 [95% confidence interval (CI) 0.62, 1.43]. Applying the American College of Cardiology and the American Heart Association (ACC/AHA) guidelines increased the proportion of HIV‐seropositive women with a statin indication from 16% to 45%. Clinicians treating HIV‐seropositive women should consider more aggressive management of the dyslipidemia often found in this population.
Scattered EXIT Charts for Finite Length LDPC Code Design

We introduce the Scattered Extrinsic Information Transfer (S-EXIT) chart as a tool for optimizing degree profiles of short length Low-Density Parity-Check (LDPC) codes under iterative decoding. As degree profile optimization is typically done in the asymptotic length regime, there is space for further improvement when considering the finite length behavior. We propose to consider the average extrinsic information as a random variable, exploiting its specific distribution properties for guiding code design. We explain, step-by-step, how to generate an S- EXIT chart for short-length LDPC codes. We show that this approach achieves gains in terms of bit error rate (BER) of 0.5 dB and 0.6 dB over the additive white Gaussian noise (AWGN) channel for codeword lengths of 128 and 180 bits, respectively, at a target BER of $10^{-4}$ when compared to conventional Extrinsic Information Transfer (EXIT) chart-based optimization. Also, a performance gain for the Binary Erasure Channel (BEC) for a block (i.e., codeword) length of 180 bits is shown.
HilE Regulates HilD by Blocking DNA Binding in Salmonella enterica Serovar Typhimurium

ABSTRACT The Salmonella type three secretion system (T3SS), encoded in the Salmonella pathogenicity island 1 (SPI1) locus, mediates the invasion of the host intestinal epithelium. SPI1 expression is dependent upon three AraC-like regulators: HilD, HilC, and RtsA. These regulators act in a complex feed-forward loop to activate each other and hilA, which encodes the activator of the T3SS structural genes. HilD has been shown to be the major integration point of most signals known to activate the expression of the SPI1 T3SS, acting as a switch to control induction of the system. HilE is a negative regulator that acts upon HilD. Here we provide genetic and biochemical data showing that HilE specifically binds to HilD but not to HilC or RtsA. This protein-protein interaction blocks the ability of HilD to bind DNA as shown by both an in vivo reporter system and an in vitro gel shift assay. HilE does not affect HilD dimerization, nor does it control the stability of the HilD protein. We also investigated the role of HilE during the infection of mice using competition assays. Although deletion of hilE does not confer a phenotype, the hilE mutation does suppress the invasion defect conferred by loss of FliZ, which acts as a positive signal controlling HilD protein activity. Together, these data suggest that HilE functions to restrict low-level HilD activity, preventing premature activation of SPI1 until positive inputs reach a threshold required to fully induce the system. IMPORTANCE Salmonella is a leading cause of gastrointestinal and systemic disease throughout the world. The SPI1 T3SS is required for Salmonella to induce inflammatory diarrhea and to gain access to underlying tissue. A complex regulatory network controls expression of SPI1 in response to numerous physiological inputs. Most of these signals impinge primarily on HilD translation or activity. The system is triggered when HilD activity crosses a threshold that allows efficient activation of its own promoter. This threshold is set by HilE, which binds to HilD to prevent the inevitable minor fluctuations in HilD activity from inappropriately activating the system. The circuit also serves as a paradigm for systems that must integrate numerous environmental parameters to control regulatory output.
Hepatitis C Virus Core-Derived Peptides Inhibit Genotype 1b Viral Genome Replication via Interaction with DDX3X

The protein DDX3X is a DEAD-box RNA helicase that is essential for the hepatitis C virus (HCV) life cycle. The HCV core protein has been shown to bind to DDX3X both in vitro and in vivo. However, the specific interactions between these two proteins and the functional importance of these interactions for the HCV viral life cycle remain unclear. We show that amino acids 16–36 near the N-terminus of the HCV core protein interact specifically with DDX3X both in vitro and in vivo. Replication of HCV replicon NNeo/C-5B RNA (genotype 1b) is significantly suppressed in HuH-7-derived cells expressing green fluorescent protein (GFP) fusions to HCV core protein residues 16–36, but not by GFP fusions to core protein residues 16–35 or 16–34. Notably, the inhibition of HCV replication due to expression of the GFP fusion to HCV core protein residues 16–36 can be reversed by overexpression of DDX3X. These results suggest that the protein interface on DDX3X that binds the HCV core protein is important for replicon maintenance. However, infection of HuH-7 cells by HCV viruses of genotype 2a (JFH1) was not affected by expression of the GFP fusion protein. These results suggest that the role of DDX3X in HCV infection involves aspects of the viral life cycle that vary in importance between HCV genotypes.
Functional Analysis of Tpr: Identification of Nuclear Pore Complex Association and Nuclear Localization Domains and a Role in mRNA Export

Tpr is a 270-kD coiled-coil protein localized to intranuclear filaments of the nuclear pore complex (NPC). The mechanism by which Tpr contributes to the structure and function of the nuclear pore is currently unknown. To gain insight into Tpr function, we expressed the full-length protein and several subdomains in mammalian cell lines and examined their effects on nuclear pore function. Through this analysis, we identified an NH2-terminal domain that was sufficient for association with the nucleoplasmic aspect of the NPC. In addition, we unexpectedly found that the acidic COOH terminus was efficiently transported into the nuclear interior, an event that was apparently mediated by a putative nuclear localization sequence. Ectopic expression of the full-length Tpr caused a dramatic accumulation of poly(A)+ RNA within the nucleus. Similar results were observed with domains that localized to the NPC and the nuclear interior. In contrast, expression of these proteins did not appear to affect nuclear import. These data are consistent with a model in which Tpr is tethered to intranuclear filaments of the NPC by its coiled coil domain leaving the acidic COOH terminus free to interact with soluble transport factors and mediate export of macromolecules from the nucleus.
Urea and lipid extraction treatment effects on δ(15)N and δ(13)C values in pelagic sharks.

RATIONALE Stable isotope analysis (SIA) provides a powerful tool to investigate diverse ecological questions for marine species, but standardized values are required for comparative assessments. For elasmobranchs, their unique osmoregulatory strategy involves retention of (15)N-depleted urea in body tissues and this may bias δ(15)N values. This may be a particular problem for large predatory species, where δ(15)N discrimination between predator and consumed prey can be small. METHODS We evaluated three treatments (deionized water rinsing [DW], chloroform/methanol [LE] and combined chloroform/methanol and deionized water rinsing [LE+DW]) applied to white muscle tissue of 125 individuals from seven pelagic shark species to (i) assess urea and lipid effects on stable isotope values determined by IRMS and (ii) investigate mathematical normalization of these values. RESULTS For all species examined, the δ(15)N values and C:N ratios increased significantly following all three treatments, identifying that urea removal is required prior to SIA of pelagic sharks. The more marked change in δ(15)N values following DW (1.3 ± 0.4‰) and LE+DW (1.2 ± 0.6‰) than following LE alone (0.7 ± 0.4‰) indicated that water rinsing was more effective at removing urea. The DW and LE+DW treatments lowered the %N values, resulting in an increase in C:N ratios from the unexpected low values of <2.6 in bulk samples to ~3.1 ± 0.1, the expected value of protein. The δ(13)C values of all species also increased significantly following LE and LE+DW treatments. CONCLUSIONS Given the mean change in δ(15)N(1.2 ± 0.6‰) and δ(13)C values (0.7 ± 0.4‰) across pelagic shark species, it is recommended that muscle tissue samples be treated with LE+DW to efficiently extract both urea and lipids to standardize isotopic values. Mathematical normalization of urea and lipid-extracted δ(15)N(LE+DW) and δ(13)C(LE+DW) values using the lipid-extracted δ(15)N(LE) and δ(13)C(LE) data were established for all pelagic shark species.
Beyond Thermodynamic Constraints: Evolutionary Sampling Generates Realistic Protein Sequence Variation

The computational design of protein sequences has yielded major successes in several application areas. However, when the principles of protein design are applied to molecular evolution, results tend to be poor. Biological evolution generates a surprising amount of site-specific variability in protein sequences. Yet, attempts at modeling this process have been only moderately successful, and current models based on protein structural metrics explain, at best, 60% of the observed variation. Surprisingly, simple measures of protein structure, such as solvent accessibility, are often better predictors of site-specific variability than more complex models employing all-atom energy functions and detailed structural modeling. We suggest here that these more complex models perform poorly because they lack consideration of the evolutionary process, which is, in part, captured by the simpler metrics. We compare protein sequences that are computationally designed to sequences that are computationally evolved using the same protein-design energy function and to homologous natural sequences. We find that, by a wide variety of metrics, evolved sequences are much more similar to natural sequences than are designed sequences. In particular, designed sequences are too conserved on the protein surface relative to natural sequences, whereas evolved sequences are not. Our results suggest that evolutionary simulation produces a realistic sampling of sequence space. By contrast, protein design—at least as currently implemented—does not. Existing energy functions seem to be sufficiently accurate to correctly describe the key thermodynamic constraints acting on protein sequences, but they need to be paired with realistic sampling schemes to generate realistic sequence alignments.
Diffusivity measurements of volatile organics in levitated viscous aerosol particles

Abstract. Field measurements indicating that atmospheric secondary organic aerosol (SOA) particles can be present in a highly viscous, glassy state have spurred numerous studies addressing low diffusivities of water in glassy aerosols. The focus of these studies is on kinetic limitations of hygroscopic growth and the plasticizing effect of water. In contrast, much less is known about diffusion limitations of organic molecules and oxidants in viscous matrices. These may affect atmospheric chemistry and gas–particle partitioning of complex mixtures with constituents of different volatility. In this study, we quantify the diffusivity of a volatile organic in a viscous matrix. Evaporation of single particles generated from an aqueous solution of sucrose and small amounts of volatile tetraethylene glycol (PEG-4) is investigated in an electrodynamic balance at controlled relative humidity (RH) and temperature. The evaporative loss of PEG-4 as determined by Mie resonance spectroscopy is used in conjunction with a radially resolved diffusion model to retrieve translational diffusion coefficients of PEG-4. Comparison of the experimentally derived diffusivities with viscosity estimates for the ternary system reveals a breakdown of the Stokes–Einstein relationship, which has often been invoked to infer diffusivity from viscosity. The evaporation of PEG-4 shows pronounced RH and temperature dependencies and is severely depressed for RH ≲ 30 %, corresponding to diffusivities
Constructing and testing a disability index in a US sample of preschoolers with disabilities

Purpose. To develop and test an index of disability severity in a heterogeneous population of preschoolers with disabilities. Method. Using a nationally representative sample of 3104 children receiving special education services in the US, questions from a parent interview were used to develop an index of disability severity consisting of domains of functioning defined by gradients of severity. Regressions were used to examine the association between 15 functional domains and 8 cognitive, social/behavioural, and functional outcomes. Full and abbreviated versions of this disability index were compared. Correlations with proxy measures of disability in this population were used to establish concurrent validity, and the predictive ability of this measure was compared with that of the federally defined disability categories. Results. Of the 15 domains examined, most were significant predictors of at least two outcomes. A shortened index of only six variables was found to be as effective as the longer version in characterising children's level of severity. The index was significantly correlated with intervention variables such as the age at which children began receiving special education or therapy service, r(2802) = −0.22, p ≤ 0.0001, the extent of modification of curriculum materials needed for the child, r(248) = 0.42, p ≤ 0.0001 and the number of services the child received in the school, r(2014) = 0.37, p ≤ 0.0001. Adding severity to special education category significantly increased the amount of variance in outcomes over special education category alone. Conclusions. These results provide evidence for the importance of the construct of severity of disability and its measurement, particularly when conducting research with very young children.
Sup-norm convergence rate and sign concentration property of Lasso and Dantzig estimators

We derive the l! convergence rate simultaneously for Lasso and Dantzig estimators in a high-dimensional linear regression model under a mutual coherence assumption on the Gram matrix of the design and two di! erent assumptions on the noise: Gaussian noise and general noise with finite variance. Then we prove that simultaneously the thresholded Lasso and Dantzig estimators with a proper choice of the threshold enjoy a sign concentration property provided that the non-zero components of the target vector are not too small.
Importance of the Saharan heat low in controlling the North Atlantic free tropospheric humidity budget deduced from IASI δd observations

The isotopic composition of water vapour in the North Atlantic free troposphere is investigated with Infrared Atmospheric Sounding Interferometer (IASI) measurements of the D / H ratio (δD) above the ocean. We show that in the vicinity of West Africa, the seasonality of δD is particularly strong (130 ‰), which is related with the influence of the Saharan heat low (SHL) during summertime. The SHL indeed largely influences the dynamic in that region by producing deep turbulent mixing layers, yielding a specific water vapour isotopic footprint. The influence of the SHL on the isotopic budget is analysed on various time and space scales and is shown to be large, highlighting the importance of the SHL dynamics on the moistening and the HDO enrichment of the free troposphere over the North Atlantic. The potential influence of the SHL is also investigated on the inter-annual scale as we also report important variations in δD above the Canary archipelago region. We interpret the variability in the enrichment, using backward trajectory analyses, in terms of the ratio of air masses coming from the North Atlantic and air masses coming from the African continent. Finally, the interest of IASI high sampling capabilities is further illustrated by presenting spatial distributions of δD and humidity above the North Atlantic from which we show that the different sources and dehydration pathways controlling the humidity can be disentangled thanks to the added value of δD observations. More generally, our results demonstrate the utility of δD observations obtained from the IASI sounder to gain insight into the hydrological cycle processes in the West African region.
Hierarchical Deep Reinforcement Learning: Integrating Temporal Abstraction and Intrinsic Motivation

Learning goal-directed behavior in environments with sparse feedback is a major challenge for reinforcement learning algorithms. The primary difficulty arises due to insufficient exploration, resulting in an agent being unable to learn robust value functions. Intrinsically motivated agents can explore new behavior for its own sake rather than to directly solve problems. Such intrinsic behaviors could eventually help the agent solve tasks posed by the environment. We present hierarchical-DQN (h-DQN), a framework to integrate hierarchical value functions, operating at different temporal scales, with intrinsically motivated deep reinforcement learning. A top-level value function learns a policy over intrinsic goals, and a lower-level function learns a policy over atomic actions to satisfy the given goals. h-DQN allows for flexible goal specifications, such as functions over entities and relations. This provides an efficient space for exploration in complicated environments. We demonstrate the strength of our approach on two problems with very sparse, delayed feedback: (1) a complex discrete stochastic decision process, and (2) the classic ATARI game `Montezuma's Revenge'.
Standard Codon Substitution Models Overestimate Purifying Selection for Nonstationary Data

Estimation of natural selection on protein-coding sequences is a key comparative genomics approach for de novo prediction of lineage-specific adaptations. Selective pressure is measured on a per-gene basis by comparing the rate of nonsynonymous substitutions to the rate of synonymous substitutions. All published codon substitution models have been time-reversible and thus assume that sequence composition does not change over time. We previously demonstrated that if time-reversible DNA substitution models are applied in the presence of changing sequence composition, the number of substitutions is systematically biased towards overestimation. We extend these findings to the case of codon substitution models and further demonstrate that the ratio of nonsynonymous to synonymous rates of substitution tends to be underestimated over three data sets of mammals, vertebrates, and insects. Our basis for comparison is a nonstationary codon substitution model that allows sequence composition to change. Goodness-of-fit results demonstrate that our new model tends to fit the data better. Direct measurement of nonstationarity shows that bias in estimates of natural selection and genetic distance increases with the degree of violation of the stationarity assumption. Additionally, inferences drawn under time-reversible models are systematically affected by compositional divergence. As genomic sequences accumulate at an accelerating rate, the importance of accurate de novo estimation of natural selection increases. Our results establish that our new model provides a more robust perspective on this fundamental quantity.
Silver Nanoparticles Affect Functional Bioenergetic Traits in the Invasive Red Sea Mussel Brachidontes pharaonis

We investigated the functional trait responses to 5 nm metallic silver nanoparticle (AgNPs) exposure in the Lessepsian-entry bivalve B. pharaonis. Respiration rate (oxygen consumption), heartbeat rate, and absorption efficiency were evaluated across an 8-day exposure period in mesocosmal conditions. Basal reference values from not-exposed specimens were statistically compared with those obtained from animals treated with three sublethal nanoparticle concentrations (2 μg L−1, 20 μg L−1, and 40 μg L−1). Our data showed statistically significant effects on the average respiration rate of B. pharaonis. Moreover, complex nonlinear dynamics were observed as a function of the concentration level and time. Heartbeat rates largely increased with no acclimation in animals exposed to the two highest levels with similar temporal dynamics. Eventually, a decreasing trend for absorption efficiency might indicate energetic constraints. In general, these data support the possible impact of engineered nanomaterials in marine environments and support the relevance of functional trait assessment in present and future ecotoxicological studies.