Miracle-dz/UniFAR-FTUs huggingface dataset:
Similarities in mRNA expression of peripheral blood drug metabolizing enzymes and cancer marker genes with biopsy samples of head and neck cancer patients

Abstract Purpose: To develop peripheral blood mRNA expression profiles of drug metabolizing enzymes (DMEs) as a surrogate to monitor tobacco induced head and neck squamous cell carcinoma (HNSCC), attempts were made to investigate (i) similarities in alterations with the cancer marker genes in biopsy samples and (ii) if alterations similar to that seen in biopsy samples are reflected in peripheral blood. Methods: Total RNA from eight soft gingival tissues and eight biopsy samples of HNSCC patients and total DNA and RNA from blood of healthy controls (n = 150) and HNSCC patients (n = 150) was processed for expression and genotyping studies. Blood from patients receiving chemo-radiotherapy was processed for follow-up study. Results: qRT-PCR revealed significant increase in mRNA expression of DMEs in biopsy and blood samples of HNSCC patients when compared to controls. Similar alterations were observed in cancer marker genes in these samples. Patients with variant genotypes of DMEs showed greater magnitude of alterations in mRNA expression when compared to wild type controls. Responders of chemo-radiotherapy showed significant decline in induction of mRNA expression of DMEs and cancer marker genes Conclusions: The data suggest that peripheral blood expression profiles could be used to monitor tobacco-induced HNSCC as well as the treatment response.
A Distribution-Free Shewhart Quality Control Chart Based on Signed-Ranks

Abstract Since their inception by Walter Shewhart in the late 1920s, most control chart developments have been distribution-based procedures in the sense that the process output is assumed to follow a specified probability distribution (normal for continuous measurements and binomial or Poisson for attribute data). Due to Deming's influence and their widespread adoption as one of the seven basic tools of total quality management (TQM), control charts have been applied to processes where data may be markedly nonnormal. In this article, we propose a distribution-free (or nonparametric) statistical quality control chart for monitoring a process center. The proposed chart is of the Shewhart type and is based on the signed-ranks of grouped observations. The exact false alarm rate and the in-control average run length of the proposed chart are computed by using the null distribution of the well-known Wilcoxon signed-rank statistic. The out-of-control run lengths are computed exactly for normal underlying distributions and by simulation for uniform, double exponential, and Cauchy shift alternatives. Efficiency studies show that the proposed chart is more efficient than the traditional Shewhart X-bar chart under heavy-tailed distributions (the double exponential and the Cauchy) but is less efficient under light-tailed distributions (the uniform and the normal).
Magnetically Driven Jets from Accretion Disks. I. Steady Solutions and Application to Jets/Winds in Young Stellar Objects

We solve one-dimensional steady and axisymmetric magnetohydrodynamic (MHD) equations to study basic properties of astrophysical jets from accretion disks. Assuming the configuration of the poloidal magnetic field, we solve for a wide range of parameters of the poloidal magnetic field strength in the disk. We include a thermal energy in the solution, although the jet is mainly accelerated by the magnetic force, so that we are able to obtain the mass flux of the jet and physical quantities, such as temperature, in the disk. We find that the mass flux (Ṁ) depends on the poloidal magnetic field strength of the disk (Bp0) when the toroidal component of the magnetic field (Bϕ0) is dominant near the disk surface, although it is independent of the magnetic field when the poloidal component is dominant there: Since Michel's minimum energy solution [v∝(B2p0/Ṁ)1/3] is almost satisfied in the magnetically driven jets, the terminal velocity (v∞) depends on Bp0 as v∝B1/3p0 when | Bϕ/Bp |0 ≫ 1, and as v∝B2/3p0 when | Bϕ/Bp |0 ≪ 1. When the toroidal component of the magnetic field is dominant near the disk surface (| Bϕ/Bp |0 ≫ 1), the acceleration mainly takes place after the flow speed exceeds the Alfvén speed. This means that the magnetic pressure largely contributes to the acceleration of these jets. We also study the dependence of mass flux on the other parameters, such as inclination angle of the poloidal field, the rotational velocity of the disk, and the r-dependence of the poloidal magnetic field strength along the field line, where r is the distance from the axis. We discuss the application of these models, i.e., the MHD jets from accretion disks, to jets/winds observed in young stellar objects (such as optical jets, T Tauri winds, and fast neutral winds). The mass-loss rates observed in these jets/winds will constrain the physical quantities in the disks. When the mass-loss rate is Ṁ~10−8 M☉ yr-1 and the velocity is vjet ~ 100 km s-1, the physical quantities in the disk are n0 ~ 1013 cm-3, Bp0 ~ 10 G, and T0 ~ 1000 K for a jet/wind that is produced around r0 ~ 15 R☉, and the mass of the central star is 1 M☉, where n0 is the number density, T0 is the temperature in the disk, and r0 is the radial distance from the central star.
Fashioning Women Citizens in al-Fajr: Reading the Domestic as National in a Conversation between a Mother and a Daughter, 1919–1920

ABSTRACT:When Najla Abillama published the first issue of al-Fajr (The Dawn) in Beirut in January 1919, hope infused articles that looked forward to the future of the homeland and its daughters. Key to that future was the home. Using postcolonial literary theory, Stephen Greenblatt’s notion of self-fashioning, and Nan Enstad’s definition of political subjects, this article analyzes a fictional correspondence between Salma and her daughter Mary, published in al-Fajr from late 1919 through 1920. The article argues that these letters marshal the discourse of domesticity—women as educated managers of their homes, children, and husbands—to articulate women’s roles in public, national life. Thus the mother-daughter and husband-wife relationships highlighted in the correspondence fashion women as citizens patriotically devoted to and shaped by the nation, partnered with their fellow citizens for its improvement. This analysis provides a model for reexamining the relationship between the domestic and the national in the interwar women’s press.
Transfer learning as a method to reproduce high-fidelity non-local thermodynamic equilibrium opacities in simulations

Simulations of high-energy density physics often need non-local thermodynamic equilibrium opacity data. These data, however, are expensive to produce at relatively low fidelity. It is even more so at high fidelity such that the opacity calculations can contribute 95 % of the total computation time. This proportion can even reach large proportions. Neural networks can be used to replace the standard calculations of low-fidelity data, and the neural networks can be trained to reproduce artificial, high-fidelity opacity spectra. In this work, it is demonstrated that a novel neural network architecture trained to reproduce high-fidelity krypton spectra through transfer learning can be used in simulations. Further, it is demonstrated that this can be done while achieving a relative per cent error of the peak radiative temperature of the hohlraum of approximately 1 % to 4 % while achieving a 19.4$\times$ speed up.
In silico analysis prediction of HepTH1-5 as a potential therapeutic agent by targeting tumour suppressor protein networks

Abstract Many studies reported that the activation of tumour suppressor protein, p53 induced the human hepcidin expression. However, its expression decreased when p53 was silenced in human hepatoma cells. Contrary to Tilapia hepcidin TH1-5, HepTH1-5 was previously reported to trigger the p53 activation through the molecular docking approach. The INhibitor of Growth (ING) family members are also shown to directly interact with p53 and promote cell cycle arrest, senescence, apoptosis and participate in DNA replication and DNA damage responses to suppress the tumour initiation and progression. However, the interrelation between INGs and HepTH1-5 remains unknown. Therefore, this study aims to identify the mechanism and their protein interactions using in silico approaches. The finding revealed that HepTH1-5 and its ligands had interacted mostly on hotspot residues of ING proteins which involved in histone modifications via acetylation, phosphorylation, and methylation. This proves that HepTH1-5 might implicate in an apoptosis signalling pathway and preserve the protein structure and function of INGs by reducing the perturbation of histone binding upon oxidative stress response. This study would provide theoretical guidance for the design and experimental studies to decipher the role of HepTH1-5 as a potential therapeutic agent for cancer therapy. Communicated by Ramaswamy H. Sarma
Different rules for binocular combination of luminance flicker in cortical and subcortical pathways

How does the human brain combine information across the eyes? It has been known for many years that cortical normalisation mechanisms implement ‘ocularity invariance’: equalising neural responses to spatial patterns presented either monocularly or binocularly. Here we used a novel combination of electrophysiology, psychophysics, pupillometry and computational modelling to ask whether this invariance also holds for flickering luminance stimuli with no spatial contrast. We find dramatic violations of ocularity invariance for these stimuli, both in cortex and also in the subcortical pathways that govern pupil diameter. Specifically, we find substantial binocular facilitation in both pathways with the effect being strongest in cortex. Near-linear binocular additivity (instead of ocularity invariance) was also found using a perceptual luminance matching task. Ocularity invariance is therefore not a ubiquitous feature of visual processing, and the brain appears to repurpose a generic normalisation algorithm for different visual functions by adjusting the amount of interocular suppression.
A tachykinin precursor 1 medullary circuit promoting rhythmic breathing

Rhythmic breathing is generated by neural circuits located in the brainstem. At its core is the preBötzinger Complex (preBötC), a region of the medulla, necessary for the generation of rhythmic breathing in mammals. The preBötC is comprised of various neuronal populations expressing neurokinin-1 receptors, the cognate G-protein-coupled receptor of the neuropeptide substance P (encoded by the tachykinin precursor 1 or Tac1). Neurokinin-1 receptors are highly expressed in the preBötC and destruction or deletion of neurokinin-1 receptor-expressing preBötC neurons severely impairs rhythmic breathing. Application of substance P to the preBötC stimulates breathing in rodents, however substance P is often associated with nociception and locomotion in various brain regions, suggesting that Tac1 neurons found in the preBötC may have diverse functional roles. Here, we aim to characterize the role of Tac1-expressing preBötC neurons in the generation of rhythmic breathing in vivo, as well as motor behaviors. Using a cre-lox recombination approach, we injected adeno-associated virus containing the excitatory channelrhodopsin-2 ChETA in the preBötC region of Tac1-cre mice. Using a combination of histological, optogenetics, respiratory, and behavioral assays, we defined the identity and the role of Tac1 preBötC neurons. These neurons are glutamatergic and their stimulation promotes rhythmic breathing in both anesthetized and freely moving/awake animals, but also triggers locomotion and overcomes respiratory depression by opioid drugs. Overall, our study identifies a new population of excitatory preBötC with major role in rhythmic breathing and behaviors.
Piconewton forces mediate GAIN domain dissociation of the latrophilin-3 adhesion GPCR

Latrophilins are adhesion G-protein coupled receptors (aGPCRs) that control excitatory synapse formation. aGPCRs, including latrophilins, are autoproteolytically cleaved at their GPCR-Autoproteolysis Inducing (GAIN) domain, but the two resulting fragments remain associated on the cell surface. It is thought that force-mediated dissociation of the fragments exposes a peptide that activates G-protein signaling of aGPCRs, but whether GAIN domain dissociation can occur on biologically relevant timescales and at physiological forces is unknown. Here, we show using magnetic tweezers that physiological forces dramatically accelerate the dissociation of the latrophilin-3 GAIN domain. Forces in the 1-10 pN range were sufficient to dissociate the GAIN domain on a seconds-to-minutes timescale, and the GAIN domain fragments reversibly reassociated after dissociation. Thus, mechanical force may be a key driver of latrophilin signaling during synapse formation, suggesting a physiological mechanism by which aGPCRs may mediate mechanically-induced signal transduction.
Distinct representations of innate and learned threats within the thalamic-amygdala pathway

Behavioral flexibility and timely reactions to salient stimuli are essential for survival. The subcortical thalamic-basolateral amygdala (BLA) pathway serves as a shortcut for salient stimuli ensuring rapid processing. Here, we show that BLA neuronal and thalamic axonal activity mirror the defensive behavior evoked by an innate visual threat as well as an auditory learned threat. Importantly, perturbing this pathway compromises defensive responses to both forms of threats, in that animals fail to switch from exploratory to defensive behavior. Despite the shared pathway between the two forms of threat processing, we observed noticeable differences. Blocking beta-adrenergic receptors impair the defensive response to the innate but not the learned threats. This reduced defensive response, surprisingly, is reflected in the suppression of the activity exclusively in the BLA, as the thalamic input response remains intact. Our side-by-side examination highlights the similarities and differences between innate and learned threat-processing, thus providing new fundamental insights.
A Real-Time Analysis of Protein Transport via the Twin Arginine Translocation Pathway in Response to Different Components of the Protonmotive Force in vivo

The twin arginine translocation (Tat) pathway transports folded protein across the cytoplasmic membrane in bacteria, archaea, and across the thylakoid membrane in plants as well as the inner membrane in some mitochondria. In plant chloroplasts, the Tat pathway utilizes the protonmotive force (PMF) to drive protein translocation. However, in bacteria, it has been shown that Tat transport depends only on the Δψ component of PMF in vitro. To investigate the comprehensive PMF requirement in Escherichia coli, we have developed the first real-time assay to monitor Tat transport utilizing the NanoLuc Binary Technology (NanoBiT) in E. coli spheroplasts. This luminescence assay allows for continuous monitoring of Tat transport with high-resolution, making it possible to observe subtle changes in transport in response to different treatments. By applying the NanoLuc assay, we report that, under acidic conditions, ΔpH, in addition to Δψ, contributes energetically to Tat transport in vivo in E. coli spheroplasts. These results provide novel insight into the mechanism of energy utilization by the Tat pathway.
Mathematical model of nuclear speckle morphology

Nuclear speckles are nuclear bodies consisting of populations of small and irregularly shaped droplet-like molecular condensates that contain various splicing factors. Recent experiments have shown the following morphological features of nuclear speckles: (I) Each molecular condensate contains SON and SRRM2 proteins, and MALAT1 non-coding RNA surrounds these condensates; (II) In the normal interphase of the cell cycle, these condensates are broadly distributed throughout the nucleus in multicellular organisms. In contrast, the fusion of condensates leads to the formation of strongly condensed spherical droplets when cell transcription is suppressed; (III) SON is dispersed spatially in MALAT1 knocked-down cells, whereas MALAT1 is dispersed in SON knocked-down cells by the collapse of nuclear speckles. However, the detailed interactions among molecules that reveal the mechanisms of this rich variety of morphologies remain unknown. In this study, a coarse-grained molecular dynamics model of the nuclear speckle was developed considering the dynamics of SON, SRRM2 or SRSF2, MALAT1, and pre-mRNA as representative components of condensates. The simulations reproduced the abovementioned morphological changes, by which the interaction strength among the representative components of the condensates was predicted.
Equivalence of charge imbalance and external electric fields during free energy calculations of membrane electroporation

Electric fields across lipid membranes play important roles in physiology, medicine, and biotechnology, rationalizing the wide interest in modeling transmembrane potentials in molecular dynamics simulations. Transmembrane potentials have been implemented with external electric fields or by imposing charge imbalance between the two water compartments of a stacked double-membrane system. We compare the two methods in the context of membrane electroporation, which involves a large change of membrane structure and capacitance. We show that, given that Ewald electrostatics are defined with tinfoil boundary conditions, the two methods lead to (i) identical potentials of means force (PMFs) of pore formation and expansion at various potentials, demonstrating that the two methods impose equivalent driving forces for large-scale transitions at membranes and (ii) to identical polarization of water within thin water wires or open pores, suggesting that the two methods furthermore impose equivalent local electric fields. Without tinfoil boundary conditions, effects from external fields on pore formation are spuriously suppressed or even removed. Together, our study shows that both methods, external fields and charge imbalance, are well suitable for studying large-scale transitions of lipid membranes that involve changes of membrane capacitance. However, using charge imbalance is technically more challenging for maintaining a constant transmembrane potential since it requires updating of the charges as the capacitance of the membrane changes.
Warming-induced range expansion effects on the diversity and composition of the gut microbiome: a case study with two butterflies

Species are the habitat of a diverse community of organisms, including bacteria, fungi and viruses – the microbiome. Evidence shows that many species shift and/or expand their geographical ranges following warming climate; yet, the response of host-associated microbiome communities to species range shifts has received less attention, especially in observational studies. Here, we use two British butterfly species for which detailed long-term distributional data is available, and document for the first time a variety of effects of warming-induced range expansion on the diversity and composition of their microbiome. Our results show similar diversity and species-specific responses in the evenness of the gut microbial communities in the two butterflies. However, butterflies at the expanded ranges showed (i) a larger variability in the microbiome diversity, and (ii) a smaller core community of bacteria that is to a large extent a subset of the bacterial core community in the original range. The microbiome is responsible for many aspects of the host’s physiology and growth, and for ecosystem function, so if the changes in the gut microbial communities reported here apply to other species and taxonomic groups, the potential impact to biodiversity and functioning after range expansion could be severe.
Population demographic history and evolutionary rescue: Influence of a bottleneck event

Rapid environmental change presents a significant challenge to the persistence of natural populations. Rapid adaptation that increases population growth, enabling populations that declined following severe environmental change to grow and avoid extinction, is called evolutionary rescue. Numerous studies have shown that evolutionary rescue can indeed prevent extinction. Here, we extend those results by considering the demographic history of populations. To evaluate how demographic history influences evolutionary rescue, we created 80 populations of red flour beetle, Tribolium castaneum, with three classes of demographic history: diverse populations that did not experience a bottleneck, and populations that experienced either an intermediate or a strong bottleneck. We subjected these populations to a new and challenging environment for six discrete generations and tracked extinction and population size. Populations that did not experience a bottleneck in their demographic history avoided extinction entirely, while more than 20% of populations that experienced an intermediate or strong bottleneck went extinct. Similarly, among the extant populations at the end of the experiment, adaptation increased the growth rate in the novel environment the most for populations that had not experienced a bottleneck in their history. Taken together, these results highlight the importance of considering the demographic history of populations to make useful and effective conservation decisions and management strategies for populations experiencing environmental change that pushes them toward extinction.
Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic: results from the Multi‐centre cohort study evaluating the role of Inflammatory Markers In patients presenting with acute ureteric Colic (MIMIC) study

To assess the relationship of white blood cell count (WBC) and other routinely collected inflammatory and clinical markers including stone size, stone position, and medical expulsive therapy use (MET), with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic, as there are conflicting data on the role of WBC and other inflammatory markers in SSP in patients with acute ureteric colic.
Single-cell Genome-and-Transcriptome sequencing without upfront whole-genome amplification reveals cell state plasticity of melanoma subclones

Single-cell multi-omics methods are enabling the study of cell state diversity, which is largely determined by the interplay of the genome, epigenome, and transcriptome. Here, we describe Gtag&T-seq, a genome-and-transcriptome sequencing (G&T-seq) protocol of the same single cells that omits whole-genome amplification (WGA) by using direct genomic tagmentation (Gtag). Gtag drastically decreases the cost and improves coverage uniformity at both the single-cell and pseudo-bulk level when compared to WGA-based G&T-seq. We also show that transcriptome-based DNA copy number inference has limited resolution and accuracy, underlining the importance of affordable multi-omic approaches. Moreover, applying Gtag&T-seq to a melanoma xenograft model before treatment and at minimal residual disease revealed differential cell state plasticity and treatment response between cancer subclones. In summary, Gtag&T-seq is a low-cost and accurate single-cell multi-omics method enabling the exploration of genetic alterations and their functional consequences in single cells at scale.