Miracle-dz/UniFAR-FTUs huggingface dataset:
SNAIL1-mediated downregulation of FOXA proteins facilitates the inactivation of transcriptional enhancer elements at key epithelial genes in colorectal cancer cells

Phenotypic conversion of tumor cells through epithelial-mesenchymal transition (EMT) requires massive gene expression changes. How these are brought about is not clear. Here we examined the impact of the EMT master regulator SNAIL1 on the FOXA family of transcription factors which are distinguished by their particular competence to induce chromatin reorganization for the activation of transcriptional enhancer elements. We show that the expression of SNAIL1 and FOXA genes is anticorrelated in transcriptomes of colorectal tumors and cell lines. In cellular EMT models, ectopically expressed Snail1 directly represses FOXA1 and triggers downregulation of all FOXA family members, suggesting that loss of FOXA expression promotes EMT. Indeed, cells with CRISPR/Cas9-induced FOXA-deficiency acquire mesenchymal characteristics. Furthermore, ChIP-seq data analysis of FOXA chromosomal distribution in relation to chromatin structural features which characterize distinct states of transcriptional activity, revealed preferential localization of FOXA factors to transcriptional enhancers at signature genes that distinguish epithelial from mesenchymal colon tumors. To validate the significance of this association, we investigated the impact of FOXA factors on structure and function of enhancers at the CDH1, CDX2 and EPHB3 genes. FOXA-deficiency and expression of dominant negative FOXA2 led to chromatin condensation at these enhancer elements. Site-directed mutagenesis of FOXA binding sites in reporter gene constructs and by genome-editing in situ impaired enhancer activity and completely abolished the active chromatin state of the EPHB3 enhancer. Conversely, expression of FOXA factors in cells with inactive CDX2 and EPHB3 enhancers led to chromatin opening and de novo deposition of the H3K4me1 and H3K27ac marks. These findings establish the pioneer function of FOXA factors at enhancer regions of epithelial genes and demonstrate their essential role in maintaining enhancer structure and function. Thus, by repressing FOXA family members, SNAIL1 targets transcription factors at strategically important positions in gene-regulatory hierarchies, which may facilitate transcriptional reprogramming during EMT.
Protein charge and mass contribute to the spatio‐temporal dynamics of protein–protein interactions in a minimal proteome

We constructed and simulated a “minimal proteome” model using Langevin dynamics. It contains 206 essential protein types that were compiled from the literature. For comparison, we generated six proteomes with randomized concentrations. We found that the net charges and molecular weights of the proteins in the minimal genome are not random. The net charge of a protein decreases linearly with molecular weight, with small proteins being mostly positively charged and large proteins negatively charged. The protein copy numbers in the minimal genome have the tendency to maximize the number of protein–protein interactions in the network. Negatively charged proteins that tend to have larger sizes can provide a large collision cross‐section allowing them to interact with other proteins; on the other hand, the smaller positively charged proteins could have higher diffusion speed and are more likely to collide with other proteins. Proteomes with random charge/mass populations form less stable clusters than those with experimental protein copy numbers. Our study suggests that “proper” populations of negatively and positively charged proteins are important for maintaining a protein–protein interaction network in a proteome. It is interesting to note that the minimal genome model based on the charge and mass of Escherichia coli may have a larger protein–protein interaction network than that based on the lower organism Mycoplasma pneumoniae.
Smooth Muscle Model For Functional Electrical Stimulation Applications

We present a new model of smooth muscle that can be used to simulate the effect of Functional Electrical Stimulation (FES). It is composed of a set of differential equations based on the physiological reality so that parameter's values are meaningful and can be used for quantitative and objective evaluation of the muscle state. Moreover, the model has an input controlled by an FES signal so that it can simulate the behavior of the muscle under artificial stimulation. We apply this model to the simulation of the bladder contraction through the detrusor stimulation. It shows that the model is able to predict the time response, the intravesical pressure and the necessary time to empty the bladder. Simulations show consistent data with the literature. These preliminary results, after in vivo validations, will be used to characterise bladders that need to be stimulated, for instance for paraplegics, and then to optimize the needed stimulation when neuroprosthesis are used to restore the emptying function.
Long‐Term Persistence of Donor Alveolar Macrophages in Human Lung Transplant Recipients That Influences Donor‐Specific Immune Responses

Steady‐state alveolar macrophages (AMs) are long‐lived lung‐resident macrophages with sentinel function. Evidence suggests that AM precursors originate during embryogenesis and populate lungs without replenishment by circulating leukocytes. However, their presence and persistence are unclear following human lung transplantation (LTx). Our goal was to examine donor AM longevity and evaluate whether AMs of recipient origin seed the transplanted lungs. Origin of AMs was accessed using donor–recipient HLA mismatches. We demonstrate that 94–100% of AMs present in bronchoalveolar lavage (BAL) were donor derived and, importantly, AMs of recipient origin were not detected. Further, analysis of BAL cells up to 3.5 years post‐LTx revealed that the majority of AMs (>87%) was donor derived. Elicitation of de novo donor‐specific antibody (DSA) is a major post‐LTx complication and a risk factor for development of chronic rejection. The donor AMs responded to anti‐HLA framework antibody (Ab) with secretion of inflammatory cytokines. Further, in an experimental murine model, we demonstrate that adoptive transfer of allogeneic AMs stimulated humoral and cellular immune responses to alloantigen and lung‐associated self‐antigens and led to bronchiolar obstruction. Therefore, donor‐derived AMs play an essential role in the DSA‐induced inflammatory cascade leading to obliterative airway disease of the transplanted lungs.
A self-tuning AFM imaging method based on data-driven mechanism

When an atomic force microscope (AFM) is utilized to scan a sample, it is usually difficult to tune and seek out suitable control gains to achieve good imaging performance, which has been a great challenge for inexperienced operators. This paper addresses this problem, and it presents an AFM imaging method with the feat of control gains self-tuning by the utilization of some data-driven mechanism. Specifically, the CARIMA model is introduced to describe the linearized AFM system, whose parameters are identified by the data-driven technology. Then, the GPC-based optimization method is adopted to calculate PI controller parameters on-line, which yields an AFM imaging method with control gains self-tuning mechanism. Finally some verification simulation is implemented, whose result demonstrates that when the scanning speed is changed or the control parameters are chosen improperly, the proposed method adjusts the control gains automatically to reduce the control error and improve the imaging accuracy.
Combined Vascular Endothelial Growth Factor Receptor/Epidermal Growth Factor Receptor Blockade with Chemotherapy for Treatment of Local, Uterine, and Metastatic Soft Tissue Sarcoma

Purpose: Soft tissue sarcoma (STS) is a rare heterogeneous malignancy. Overall survival has been stagnant for decades, primarily because systemic therapies are ineffective versus metastases, the leading cause of STS lethality. Consequently, we examined whether tyrosine kinase receptors active in STS growth signaling might be blockable and whether multireceptor blockade might synergize with low-dose STS chemotherapy by therapeutically affecting STS cells and their associated microenvironment. Experimental Design: Vandetanib (AstraZenca), a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor, was evaluated alone and with chemotherapy in vitro and in vivo in three human STS nude mouse xenograft models of different STS locations (muscle, uterus, lung), stages (primary, metastatic), and subtypes (leiomyosarcoma, fibrosarcoma, uterine sarcoma: luciferase-expressing MES-SA human uterine sarcoma cells surgically implanted into uterine muscularis with bioluminescence tumor growth assessment; developed by us). Results:In vitro, human STS cells were sensitive to vandetanib. Vandetanib alone and with chemotherapy statistically significantly inhibited leiomyosarcoma local growth and fibrosarcoma lung metastasis. Direct injection of MES-SA into nude mice uterine muscularis resulted in high tumor take (88%), whereas s.c. injection resulted in no growth, suggesting microenvironmental tumor growth modulation. Vandetanib alone and with chemotherapy statistically significantly inhibited uterine sarcoma growth. In all models, vandetanib induced increased apoptosis, decreased tumor cell proliferation, and decreased angiogenesis. Conclusions: Vandetanib has antitumor effects against human STS subtypes in vitro and in vivo, where it also affects the tumor-associated microenvironment. Given the urgent need for better systemic approaches to STS, clinical trials evaluating vandetanib, perhaps with low-dose chemotherapy, seem warranted.
All season assessment of RADARSAT Constellation Mission compact polarimetry modes for canadian ICE service operational implementation

The RADARSAT Constellation Mission (RCM) will have the capability of acquiring all of its beam modes in a compact polarimetry (CP) configuration. The RCM SAR will transmit circular polarization and receive two orthogonal mutually coherent linear polarizations at swath widths large enough for operational sea ice monitoring. CP parameters are synthesized from RADARSAT-2 quad-polarized data, to emulate three RCM modes at different resolutions and noise floors. From an initial set of 26 CP parameters and 5 standard parameters, the most promising parameters for sea ice type and open water discrimination are identified for each ice season, using two-sample Kolmogorov-Smirnov testing. The most promising parameters are further analyzed to assess their suitability for automated classification while qualitative analysis is also performed to assess the interpretive improvement of CP parameters over standard co- and cross-polarized imagery.
In situ demonstration of mature oligodendrocytes and their processes: An immunocytochemical study with a new monoclonal antibody, Rip

This paper introduces “Rip” a monoclonal antibody that produces relatively complete staining of oligodendrocytes and their processes in the adult central nervous system (CNS). The distribution of Rip immunoreactivity coincides with that of myelinated axons in both the spinal cord and the cerebellum. In addition, doubleimmunolabeling experiments demonstrate that Rip stains processes containing myelin basic protein but does not stain processes that express glial fibrillary acidic protein. These results indicate that Rip selectively stains oligodendrocytes but not astrocytes. Moreover, individual Rip‐stained oligodendroglial somata and their cytoplasmic processes were observable at both the light microscopic and electron microscopic level when the staining of myelin was reduced. This was accomplished by omitting detergents from antibody incubation steps. Rip‐stained oligodendrocytes have multiple processes of varying thickness, some of which end in close proximity to myelin sheaths. These immunostained profiles, reminiscent of those observed in oligodendrocytes stained by Golgi methods, are unique to Rip and indicate that its immunoreactivity is distinct from that of existing serological markers for oligodendrocytes.
Reduced BPTI is collapsed. A pulsed field gradient NMR study of unfolded and partially folded bovine pancreatic trypsin inhibitor

Pulsed field gradient NMR was used to measure the hydrodynamic behavior of unfolded variants of bovine pancreatic trypsin inhibitor (BPTI). The unfolded BPTI species studied were [R]Abu, at pH 4.5 and pH 2.5, and unfolded [14‐38]Abu at pH 2.5. These were prepared by chemical synthesis. [R]Abu is a model for reduced BPTI; all cysteine residues are replaced by α‐amino‐n‐butyric acid (Abu). [14‐38]Abu retains cysteines 14 and 38, which form a disulfide bond, while the other cysteine residues are replaced by Abu. In the PFG experiments, the diffusion coefficient is measured as a function of protein concentration, and the value of D°—the diffusion coefficient extrapolated to infinite dilution—is determined. From D°, a value of the hydrodynamic radius, Rh, is computed from the Stokes‐Einstein relationship. At pH 4.5, [R]Abu has an Rh value significantly less than the value calculated for a random coil, while at pH 2.5 the experimental Rh value is the same as for a random coil. In view of the changes in NMR‐detected structure of [R]Abu at pH 4.5 versus pH 2.5 (Pan H, Barbar E, Barany G, Woodward C. 1995. Extensive non‐random structure in reduced and unfolded bovine pancreatic trypsin inhibitor. Biochemistry 34:13974‐13981), the collapse of reduced BPTI at pH 4.5 may be associated with the formation of non‐native hydrophobic clusters of pairs of side chains one to three amino acids apart in sequence. The diffusion constant of [14‐38]Abu was also measured at pH 4.5, where the protein is partially folded. An increase in hydrodynamic radius of partially folded [14‐38]Abu relative to native BPTI, is similar to the increase in radius of gyration measured for other proteins under “molten globule” conditions.
FDMA with Layers-based Optimized Mobile Relays Subsets Algorithm in B5G/6G Cognitive IoT Networks

In view of noteworthy communications performance improvements for future B5G/6G (such as cognitive Internet of Things, space-ground integration network and so on), cooperative communications (CC) diversity with relays selection algorithms have been extensively studied to significantly improve communications quality, but so far there is still a lot of potential optimization work with CC schemes. In this paper, in the light of NP-hard problem of subsets relays selection, further studies for theorems of relays subsets with K-layers power allocation standard have been put forward to explore better performance in B5G/6G cognitive IoT (Internet of Things) networks, we propose unified layers-based optimized mobile relays subsets algorithms for full-duplex (FD) non-orthogonal multiple access (NOMA) to greatly improve transmission rate. After revealing and taking into account fundamental properties of relays, such as mobile relays nodes state, relays locations, fading characteristics and so on, optimized FD-NOMA algorithm based on these relays features has been presented to improve transmission validity, and a related series of relays subsets theorems have been derived and proved, then minimum upper bound of maximum transmission rates has been estimated to reveal two-way balanced optimal transmission conclusion for FD-NOMA. In general, proposed general and optimized algorithm can be used in multiple future cooperative communications scenarios in B5G/6G networks such as cognitive IoT. Simulations results show that proposed scheme has several times transmission rates than other classical relays selection algorithms
Characterization and stability studies of bioactive compounds and food matrices as evidence in support of health claims

Abstract The characterization and stability evaluation of food and food constituents (chemical active ingredient/microorganism) for which nutrition or health claims want to be requested are essential for the success of an application to EFSA. This work reviews the requirements that must be fulfilled for a full characterization of the active substance, comprising origin, elaboration, or extraction method, and chemical/microbiological composition, using validated analytical methods. The review focuses not only on establishing the specifications of the final active ingredient or food but also on ensuring homogeneity between batches. In addition, the article discusses the methodologies and conditions of the stability studies that need to be performed on food and food constituents to verify that the relevant compounds – chemical and microbiological active ingredients – will get to the consumer in the intended state and concentration to accomplish the claimed health effect over shelf life.
hnRNP C Is Required for Postimplantation Mouse Development but Is Dispensable for Cell Viability

ABSTRACT The hnRNP C1 and C2 proteins are among the most abundant proteins in the nucleus, and as ubiquitous components of RNP complexes, they have been implicated in many aspects of mRNA biogenesis. In this report, we have characterized a null mutation induced in embryonic stem cells by insertion of the U3His gene trap retrovirus into the first intron of the hnRNP C1/C2 gene. cDNAs encoding murine hnRNP C1 and C2 were characterized, and the predicted protein sequences were found to be highly conserved among vertebrates. A human consensus sequence, generated from over 400 expressed sequence tags, suggests two revisions to the previously published human sequence. In addition, alternatively spliced transcripts, expressed only by the murine gene, encode four novel proteins: variants of C1 and C2 with either seven additional amino acids or one fewer amino acid in a region between the oligomerization and C-terminal acidic domains. The disrupted gene was transmitted into the germ line and is tightly linked to a recessive, embryonic lethal phenotype. Homozygous mutant embryos fail to develop beyond the egg cylinder stage and are resorbed by 10.5 days of gestation, a phenotype consistent with a fundamental role in cellular metabolism. However, hnRNP C1 and C2 are not required for cell viability. Embryonic stem cell lines established from homozygous mutant blastocysts did not express detectable levels of either protein yet were able to grow and differentiate in vitro, albeit more slowly than wild-type cells. These results indicate that the C1 and C2 hnRNPs are not required for any essential step in mRNA biogenesis; however, the proteins may influence the rate and/or fidelity of one or more steps.
Cooperative spectrum sensing over generalized fading channels based on energy detection

This paper analyzes the unified performance of energy detection (ED) of spectrum sensing (SS) over generalized fading channels in cognitive radios (CRs). The detective performance of SS will be obviously affected by fading channels among communication nodes, and ED has the advantages of fast implementation, no requirement of priori received information and low complexity, so it is meaningful to investigate ED over various fading channels. The probability density function (p.d.f.) of α-κ-μ distribution is derived to evaluate energy efficiency for sensing systems. The detection probability with Marcum-Q function has been derived and the close-form expressions with moment generating function (MGF) method are deduced to achieve SS. Furthermore, exact closed-form analytic expressions for average area under the receiver operating characteristics curve (AUC) also have been deduced to analyze the performance characteristics of ED over α-κ-μ fading channels. Besides, cooperative spectrum sensing (CSS) with diversity reception has been applied to improve the detection accuracy and mitigate the shadowed fading features with OR-rule. At last, the results show that the detection capacity of ED will be evidently affected by α-κ-μ fading channels, but appropriate channel parameters can improve sensing performance. In addition, the established ED-fading pattern is approved by simulations, and it can significantly enhance the detection performance of proposed algorithms.
Within-Host Evolution Results in Antigenically Distinct GII.4 Noroviruses

ABSTRACT Genogroup II, genotype 4 (GII.4) noroviruses are known to rapidly evolve, with the emergence of a new primary strain every 2 to 4 years as herd immunity to the previously circulating strain is overcome. Because viral genetic diversity is higher in chronic than in acute infection, chronically infected immunocompromised people have been hypothesized to be a potential source for new epidemic GII.4 strains. However, while some capsid protein residues are under positive selection and undergo patterned changes in sequence variation over time, the relationships between genetic variation and antigenic variation remains unknown. Based on previously published GII.4 strains from a chronically infected individual, we synthetically reconstructed virus-like particles (VLPs) representing early and late isolates from a small-bowel transplant patient chronically infected with norovirus, as well as the parental GII.4-2006b strain. We demonstrate that intrahost GII.4 evolution results in the emergence of antigenically distinct strains over time, comparable to the variation noted between the chronologically predominant GII.4 strains GII.4-2006b and GII.4-2009. Our data suggest that in some individuals the evolution that occurs during a chronic norovirus infection overlaps with changing antigenic epitopes that are associated with successive outbreak strains and may select for isolates that are potentially able to escape herd immunity from earlier isolates. IMPORTANCE Noroviruses are agents of gastrointestinal illness, infecting an estimated 21 million people per year in the United States alone. In healthy individuals, symptomatic infection typically resolves within 24 to 48 h. However, symptoms may persist for years in immunocompromised individuals, and development of successful treatments for these patients is a continuing challenge. This work is relevant to the design of successful norovirus therapeutics for chronically infected patients; provides support for previous assertions that chronically infected individuals may serve as reservoirs for new, antigenically unique emergent strains; and furthers our understanding of genogroup II, genotype 4 (GII.4) norovirus immune-driven molecular evolution.
Common Factors That Enhance the Quality of Life for Women Living in Their Own Homes or in Aged Care Facilities

A qualitative study of older women living in their own homes and older women living in aged care facilities found that the concerns of the women living in their own homes were the realities of life for the residents in the aged care facilities. Twenty-five female residents across two facilities and 11 older women living in their own homes were interviewed. The positive outcomes of aging at home are relevant and desirable for residents of aged care facilities. A smooth transition from community living to residential aged care involves retaining some of these positive aspects of their lives.