Miracle-dz/UniFAR-FTUs huggingface dataset:
TNFAIP8 promotes prostate cancer cell survival by inducing autophagy

Tumor necrosis factor-α-inducible protein 8 (TNFAIP8) is a TNF-α inducible anti-apoptotic protein with multiple roles in tumor growth and survival. Mechanisms of cell survival by TNFAIP8 remain elusive. We investigated the role of TNFAIP8 in the regulation of the cell cycle, autophagy, cell survival and neuroendocrine differentiation in prostate cancer cells. We showed that TNFAIP8 dysregulates cell-cycle-related proteins, in PC3 cells. Oncogenic cell survival, drug resistance and dysregulation of cell cycle-related proteins are often associated with autophagy. We demonstrated that TNFAIP8 induces autophagy by increasing expression of autophagy effectors such as LC3β I/II, Beclin1, 4EBP1, p62, and SIRT1. We also demonstrated that TNFAIP8 interacts with autophagy-related protein 3 (ATG3). TNFα treatment increased the expression of TNFAIP8, which was associated with increased autophagy and decreased apoptosis. We also observed an increase in expression of neuroendocrine differentiation markers, synaptophysin and chromogranin A, and drug resistance to anticancer drugs, docetaxel and doxorubicin, in cells transfected with TNFAIP8. Collectively, our findings reveal that by the creation of cellular autophagy events, TNFAIP8 promotes cell survival and drug resistance in prostate cancer cells.
Bioinformatic analysis of the fold type I PLP‐dependent enzymes reveals determinants of reaction specificity in l‐threonine aldolase from Aeromonas jandaei

Understanding the role of specific amino acid residues in the molecular mechanism of a protein's function is one of the most challenging problems in modern biology. A systematic bioinformatic analysis of protein families and superfamilies can help in the study of structure–function relationships and in the design of improved variants of enzymes/proteins, but represents a methodological challenge. The pyridoxal‐5′‐phosphate (PLP)‐dependent enzymes are catalytically diverse and include the aspartate aminotransferase superfamily which implements a common structural framework known as type fold I. In this work, the recently developed bioinformatic online methods Mustguseal and Zebra were used to collect and study a large representative set of the aspartate aminotransferase superfamily with high structural, but low sequence similarity to l‐threonine aldolase from Aeromonas jandaei (LTAaj), in order to identify conserved positions that provide general properties in the superfamily, and to reveal family‐specific positions (FSPs) responsible for functional diversity. The roles of the identified residues in the catalytic mechanism and reaction specificity of LTAaj were then studied by experimental site‐directed mutagenesis and molecular modelling. It was shown that FSPs determine reaction specificity by coordinating the PLP cofactor in the enzyme's active centre, thus influencing its activation and the tautomeric equilibrium of the intermediates, which can be used as hotspots to modulate the protein's functional properties. Mutagenesis at the selected FSPs in LTAaj led to a reduction in a native catalytic activity and increased the rate of promiscuous reactions. The results provide insight into the structural basis of catalytic promiscuity of the PLP‐dependent enzymes and demonstrate the potential of bioinformatic analysis in studying structure–function relationship in protein superfamilies.
Mycobacterium tuberculosis Invasion of the Human Lung: First Contact

Early immune responses to Mycobacterium tuberculosis (Mtb) invasion of the human lung play a decisive role in the outcome of infection, leading to either rapid clearance of the pathogen or stable infection. Despite their critical impact on health and disease, these early host–pathogen interactions at the primary site of infection are still poorly understood. In vitro studies cannot fully reflect the complexity of the lung architecture and its impact on host–pathogen interactions, while animal models have their own limitations. In this study, we have investigated the initial responses in human lung tissue explants to Mtb infection, focusing primarily on gene expression patterns in different tissue-resident cell types. As first cell types confronted with pathogens invading the lung, alveolar macrophages, and epithelial cells displayed rapid proinflammatory chemokine and cytokine responses to Mtb infection. Other tissue-resident innate cells like gamma/delta T cells, mucosal associated invariant T cells, and natural killer cells showed partially similar but weaker responses, with a high degree of variability across different donors. Finally, we investigated the responses of tissue-resident innate lymphoid cells to the inflammatory milieu induced by Mtb infection. Our infection model provides a unique approach toward host–pathogen interactions at the natural port of Mtb entry and site of its implantation, i.e., the human lung. Our data provide a first detailed insight into the early responses of different relevant pulmonary cells in the alveolar microenvironment to contact with Mtb. These results can form the basis for the identification of host markers that orchestrate early host defense and provide resistance or susceptibility to stable Mtb infection.
An ensemble framework for time delay synchronization

Synchronization based state estimation tries to synchronize a model with the true evolution of a system via the observations. In practice, an extra term is added to the model equations which hampers growth of instabilities transversal to the synchronization manifold. Therefore, there is a very close connection between synchronization and data assimilation. Recently, synchronization with time‐delayed observations has been proposed, in which observations at future times are used to help synchronize a system that does not synchronize using only present observations, with remarkable successes. Unfortunately, these schemes are limited to small‐dimensional problems.
Neurocranial anatomy of the petalichthyid placoderm Shearsbyaspis oepiki Young revealed by X‐ray computed microtomography

Stem‐group gnathostomes reveal the sequence of character acquisition in the origin of modern jawed vertebrates. The petalichthyids are placoderm‐grade stem‐group gnathostomes known from both isolated skeletal material and rarer articulated specimens of one genus. They are of particular interest because of anatomical resemblances with osteostracans, the jawless sister group of jawed vertebrates. Because of this, they have become central to debates on the relationships of placoderms and the primitive cranial architecture of gnathostomes. However, among petalichthyids, only the braincase of Macropetalichthys has been studied in detail, and the diversity of neurocranial morphology in this group remains poorly documented. Using X‐ray computed microtomography, we investigated the endocranial morphology of Shearsbyaspis oepiki Young, a three‐dimensionally preserved petalichthyid from the Early Devonian of Taemas‐Wee Jasper, Australia. We generated virtual reconstructions of the external endocranial surfaces, orbital walls and cranial endocavity, including canals for major nerves and blood vessels. The neurocranium of Shearsbyaspis resembles that of Macropetalichthys, particularly in the morphology of the brain cavity, nerves and blood vessels. Many characters, including the morphology of the pituitary vein canal and the course of the trigeminal nerve, recall the morphology of osteostracans. Additionally, the presence of a parasphenoid in Shearsbyaspis (previously not known with confidence outside of arthrodires and osteichthyans) raises some questions about current proposals of placoderm paraphyly. Our detailed description of this specimen adds to the known morphological diversity of petalichthyids, and invites critical reappraisal of the phylogenetic relationships of placoderms.
Soil Moisture‐Temperature Coupling in a Set of Land Surface Models

The land surface controls the partitioning of water and energy fluxes and therefore plays a crucial role in the climate system. The coupling between soil moisture and air temperature, in particular, has been shown to affect the severity and occurrence of temperature extremes and heat waves. Here we study soil moisture‐temperature coupling in five land surface models, focusing on the terrestrial segment of the coupling in the warm season. All models are run off‐line over a common period with identical atmospheric forcing data, in order to allow differences in the results to be attributed to the models' partitioning of energy and water fluxes. Coupling is calculated according to two semiempirical metrics, and results are compared to observational flux tower data. Results show that the locations of the global hot spots of soil moisture‐temperature coupling are similar across all models and for both metrics. In agreement with previous studies, these areas are located in transitional climate regimes. The magnitude and local patterns of model coupling, however, can vary considerably. Model coupling fields are compared to tower data, bearing in mind the limitations in the geographical distribution of flux towers and the differences in representative area of models and in situ data. Nevertheless, model coupling correlates in space with the tower‐based results (r = 0.5–0.7), with the multimodel mean performing similarly to the best‐performing model. Intermodel differences are also found in the evaporative fractions and may relate to errors in model parameterizations and ancillary data of soil and vegetation characteristics.
A phenomenological model for structural phase transitions in incommensurate alkane/urea inclusion compounds

n-Alkane/urea inclusion compounds are crystalline materials in which n-alkane ‘guest’ molecules are located within parallel one-dimensional ‘host’ tunnels formed by a helical hydrogen-bonded arrangement of urea molecules. The periodic repeat distance of the guest molecules along the host tunnels is incommensurate with the periodic repeat distance of the host substructure. The structural properties of the high-temperature phase of these materials (phase I), which exist at ambient temperature, are described by a (3 + 1)-dimensional superspace. Recent publications have suggested that, in the prototypical incommensurate composite systems, n-nonadecane/urea and n-hexadecane/urea, two low-temperature phases II and ‘III’ exist and that one or both of these phases are described by a (3 + 2)-dimensional superspace. We present a phenomenological model based on symmetry considerations and developed in the frame of a pseudo-spin–phonon coupling mechanism, which accounts for the mechanisms responsible for the I ↔ II ↔ ‘III’ phase sequence. With reference to published experimental data, we demonstrate that, in all phases of these incommensurate materials, the structural properties are described by (3 + 1)-dimensional superspace groups. Around the temperature of the II ↔ ‘III’ transition, the macroscopic properties of the material are not actually associated with a phase transition, but instead represent a ‘crossover’ between two regimes involving different couplings between relevant order parameters.
Evidence for Pacific‐modulated precipitation variability during the late Holocene from the southwestern USA

The mechanisms driving late Holocene drought cycles in the western United States are not well known due to the general scarcity of long‐term, high‐resolution, absolutely dateable proxies for precipitation in continental interiors. Here we show that late Holocene precipitation variability in the southwestern United States has been caused by changes in the Pacific Ocean. We present a stalagmite‐based, annually resolved moisture record that indicates large shifts from pluvial to drought conditions alternating with periods of dampened, near‐average precipitation over the last 3000 years. Significant spectral peaks at decadal‐scale (∼20–50, 70–80 year) frequencies likely correspond to modern frequencies of the Pacific Decadal Oscillation or a low‐frequency component of the El Niño‐Southern Oscillation, and are dominant during episodes of large precipitation shifts. Overall pluvial conditions punctuated by severe droughts may have challenged the adaptive capacities of emerging agrarian communities of ancestral Americans.
Deep Learning Hyper-Parameter Optimization for Video Analytics in Clouds

A system to perform video analytics is proposed using a dynamically tuned convolutional network. Videos are fetched from cloud storage, preprocessed, and a model for supporting classification is developed on these video streams using cloud-based infrastructure. A key focus in this paper is on tuning hyper-parameters associated with the deep learning algorithm used to construct the model. We further propose an automatic video object classification pipeline to validate the system. The mathematical model used to support hyper-parameter tuning improves performance of the proposed pipeline, and outcomes of various parameters on system’s performance is compared. Subsequently, the parameters that contribute toward the most optimal performance are selected for the video object classification pipeline. Our experiment-based validation reveals an accuracy and precision of 97% and 96%, respectively. The system proved to be scalable, robust, and customizable for a variety of different applications.
Comparative Biochemical Study of Aloe-emodin and Barbaloin by Antioxidative and Antiglycation Evaluations in Mice Liver Tissue

Aloe vera is widely used for medicine, dietary supplements, and cosmetic purposes. In recent years, the consumption of this plant¼s juice and gel has promoted and with entering them to the body different systems are encountering their effects. Liver as an important organ may response to the main active components of this plant, Aloe-emodin and Barbaloin. The aim of the present study was to investigate the antioxidant and antiglycation properties of these compounds on mice liver tissue at concentrations ranging from 0 to 12 mM. In this study various concentrations (0-12 mM) of Aloe-emodin and Barbaloin were added to liver tissue cultures and after 24h incubation the tests were performed. Enzymatic activities, Malondialdehyde level and DPPH radicals scavenging activity were evaluated by spectrophotometric method. Dityrosine level was measured by HPLC method. Antiglycation properties were evaluated by pentosidine and glyoxal tests. in vitro studies indicated that Aloe-emodin and Barbaloin scavenged free radicals in a dose dependent manner. Also, the results revealed that Aloe-emodin and Barbaloin could increase liver antioxidant enzymes activity including superoxide dismutase, catalase, and glutathione peroxidase at low (0.75-1.5 mM) and high (3-12 mM) concentrations respectively. In other words, the levels of malondialdehyde and dityrosine, as oxidative damage biomarkers, significantly decreased at these concentrations, compared with the control value. Moreover at these doses, these two compounds had significant antiglycation property on the liver tissue as they evaluated by pentosidine and glyoxal tests. Therefore, as these compounds had significant antioxidant and antiglycation properties on the liver tissue, it can be expected that usage of them can be protected the liver tissue against chronic liver disease that is resulting from diabetes, non-alcoholic steatohepatitis (NASH).
Indigenous king of bitter (Andrographis paniculata): A review

Andrographis paniculata (King of bitters), commonly known as Kalmegh is belongs to the family of Acanthaceae. The objective of this study is to review the literature of Andrographis paniculata specifically articles pertaining to therapeutic benefits, chemical properties and pharmacological evaluation. It is extensively used in indigenous system of medicines as home remedy for various diseases in Bangladeshi traditional system. It is used to treat hepatitis, gastrointestinal tract and upper respiratory infections, fever, herpes, and a variety of other chronic and infectious diseases. Andrographis paniculata possess hepatoprotective, anti-inflammatory, immunostimulatory, antipyretic, antioxidant, hypotensive, antibacterial activities. Andrographis paniculata contains steroids, phenols, terpenoids, alkaloids, saponins, flavonoids were the active compounds present in the plant. The medicinal value of this plant is due to the presence of active ingredients viz andrographolide and neoandrographolide which are derivatives of diterpenoids.
Retina Inherited Photoreceptor Degeneration Causes the Death of Melanopsin-Positive Retinal Ganglion Cells and Increases Their Coexpression of Brn 3 a

Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca), and Departamento de Oftalmoloǵıa, Facultad de Medicina, Universidad de Murcia, Murcia, Spain Departamento de Fisioloǵıa, Genética y Microbioloǵıa, Universidad de Alicante, San Vicente del Raspeig, Alicante, Spain Servicio de Oftalmoloǵıa, Hospital Cĺınico Universitario Lozano Blesa, Zaragoza, Spain
Fatigue Influences the Recruitment, but Not Structure, of Muscle Synergies

The development of fatigue elicits multiple adaptations from the neuromuscular system. Muscle synergies are common patterns of neuromuscular activation that have been proposed as the building blocks of human movement. We wanted to identify possible adaptations of muscle synergies to the development of fatigue in the upper limb. Recent studies have reported that synergy structure remains invariant during the development of fatigue, but these studies did not examine isolated synergies. We propose a novel approach to characterize synergy adaptations to fatigue by taking advantage of the spatial tuning of synergies. This approach allows improved identification of changes to individual synergies that might otherwise be confounded by changing contributions of overlapping synergies. To analyse upper limb synergies we applied non-negative matrix factorization to 14 EMG signals from muscles of 11 participants performing isometric contractions. A preliminary multidirectional task was used to identify synergy directional tuning. A subsequent fatiguing task was designed to fatigue the participants in their synergies’ preferred directions. Both tasks provided virtual reality feedback of the applied force direction and magnitude, and were performed at 40% of each participant’s maximal voluntary force. Five epochs were analysed throughout the fatiguing task to identify progressive changes of EMG amplitude, median frequency, synergy structure, and activation coefficients. Three to four synergies were sufficient to account for the variability contained in the original data. Synergy structure was conserved with fatigue, but interestingly synergy activation coefficients decreased on average by 24.5% with fatigue development. EMG amplitude did not change systematically with fatigue, whereas EMG median frequency consistently decreased across all muscles. These results support the notion of a neuromuscular modular organization as the building blocks of human movement, with adaptations to synergy recruitment occurring with fatigue. When synergy tuning properties are considered, the reduction of activation of muscle synergies may be a reliable marker to identify fatigue.
Vitamin C in Health and Disease

Vitamins are essential to maintain normal metabolic processes and homeostasis within the body. The amount of a specific vitamin required by an individual varies considerably and it is influenced by such factors as body size, growth rate, physical activity, and pregnancy. Most vitamins are stored minimally in human cells, but some are stored in liver cells to a greater extent. Vitamins A and D, for example, may be stored in sufficient amounts to maintain an individual without any intake for 5 to 10 months and 2 to 4 months, respectively. However, a deficiency of vitamin B compounds (except vitamin B12) may be noted within days, and the lack of vitamin C will manifest within weeks and may result in death in 5 to 6 months. The current recommended dietary allowance (RDA) of vitamin C is 75 mg for woman and 90 mg for men, based on the vitamin’s role as an antioxidant as well as protection from deficiency. High intakes of the vitamin are generally well tolerated, however, a Tolerable Upper Level (TUL) was recently set at 2 g based on gastrointestinal upset that sometimes accompanies excessive dosages. Several populations warrant special attention with respect to vitamin C requirements. These include patients with periodontal disease, smokers, pregnant and lactating women, and the elderly.
Degree sequences of random digraphs and bipartite graphs

Research School of Computer ScienceAustralian National UniversityCanberra ACT 0200, Australiabdm@cs.anu. edu.au, fiona.skerman@stats.ox. ac.ukAbstractWe investigate the joint distribution of the vertex degrees in three models ofrandom bipartite graphs. Namely, we can choose each edge with a speciﬁed prob-ability, choose a speciﬁed number of edges, or specify the vertex degrees in one ofthe two colour classes.This problem can also be described in terms of the row and sum columns ofrandom binary matrix or the in-degrees and out-degrees of a random digraph, inwhich case we can optionally forbid loops. It can also be cast as a problem inrandom hypergraphs, or as a classical occupancy, allocation, or coupon collectionproblem.In each case, provided the two colour classes are not too diﬀerent in size orthe number of edges too low, we deﬁne a probability space based on independentbinomial variables and show that its probability masses asymptotically equal thoseof the degrees in the graph model almost everywhere. The accuracy is suﬃcient toasymptotically determine the expectation of any joint function of the degrees whosemaximum is at most polynomially greater than its expectation.Our starting points are theorems of Canﬁeld, Greenhill and McKay (2008–2009)that enumerate bipartite graphs by degree sequence. The resulting theory is analo-gous to that developed by McKay and Wormald (1997) for general graphs.
Built-in Vulnerabilities to Imperceptible Adversarial Perturbations

Designing models that are robust to small adversarial perturbations of their inputs has proven remarkably difficult. In this work we show that the reverse problem---making models more vulnerable---is surprisingly easy. After presenting some proofs of concept on MNIST, we introduce a generic tilting attack that injects vulnerabilities into the linear layers of pre-trained networks by increasing their sensitivity to components of low variance in the training data without affecting their performance on test data. We illustrate this attack on a multilayer perceptron trained on SVHN and use it to design a stand-alone adversarial module which we call a steganogram decoder. Finally, we show on CIFAR-10 that a poisoning attack with a poisoning rate as low as 0.1% can induce vulnerabilities to chosen imperceptible backdoor signals in state-of-the-art networks. Beyond their practical implications, these different results shed new light on the nature of the adversarial example phenomenon.