Miracle-dz/UniFAR-FTUs huggingface dataset:
Galectin-3 in Cardiovascular Diseases

Galectin-3 (Gal-3) is a β-galactoside-binding protein belonging to the lectin family with pleiotropic regulatory activities and several physiological cellular functions, such as cellular growth, proliferation, apoptosis, differentiation, cellular adhesion, and tissue repair. Inflammation, tissue fibrosis and angiogenesis are the main processes in which Gal-3 is involved. It is implicated in the pathogenesis of several diseases, including organ fibrosis, chronic inflammation, cancer, atherosclerosis and other cardiovascular diseases (CVDs). This review aims to explore the connections of Gal-3 with cardiovascular diseases since they represent a major cause of morbidity and mortality. We herein discuss the evidence on the pro-inflammatory role of Gal-3 in the atherogenic process as well as the association with plaque features linked to lesion stability. We report the biological role and molecular mechanisms of Gal-3 in other CVDs, highlighting its involvement in the development of cardiac fibrosis and impaired myocardium remodelling, resulting in heart failure and atrial fibrillation. The role of Gal-3 as a prognostic marker of heart failure is described together with possible diagnostic applications to other CVDs. Finally, we report the tentative use of Gal-3 inhibition as a therapeutic approach to prevent cardiac inflammation and fibrosis.
The publication dates of the parts-issue of Richard Thomas Lowe s A Manual Flora of Madeira (1857-1872), with a publishing history

A Manual Flora of Madeira and the Adjacent Islands of Porto Santo and the Desertas by Richard Thomas Lowe, was published in demy duodecimo parts between 1857 and 1872 by John Van Voorst. It is a classic of careful botanical description, still relevant to modern research on the flora of the Madeiran Archipelago. Because of the inclusion in the work of new taxa and other valuable historical information, it is crucial to date as precisely as possible each of the six parts (publication of which was cut short by Lowe’s death in April 1874), and to record the exact contents of each part; the work is not illustrated. The publication dates of the five parts comprising volume I were no later than: 16 November 1857 (pages [i-ii], [i]-xii, [1]-106); 31 January 1862 (pages [107]-262); 30 December 1863 (pages [263]-[378]); 4 February 1868 (pages [379]-522); 31 December 1868 (pages 523-618). Only the first part of volume II was published, no later than 31 March 1872 (pages [1]-[116]). The consolidated volume I was published in December 1868; it was subsequently combined with part I of volume II, and reissued in 1874 or later. Descriptions of the publisher’s known cloth-case designs are presented. Comments on the general reception by fellow-botanists and the publishing history of the whole work are also provided. By 1884, Van Voorst had apparently sold the remaining stock to Bernard Quaritch, the London bookseller.
Ventilation With Argon Improves Survival With Good Neurological Recovery After Prolonged Untreated Cardiac Arrest in Pigs

Background Ventilation with the noble gas argon (Ar) has shown neuroprotective and cardioprotective properties in different in vitro and in vivo models. Hence, the neuroprotective effects of Ar were investigated in a severe, preclinically relevant porcine model of cardiac arrest. Methods and Results Cardiac arrest was ischemically induced in 36 pigs and left untreated for 12 minutes before starting cardiopulmonary resuscitation. Animals were randomized to 4‐hour post‐resuscitation ventilation with: 70% nitrogen–30% oxygen (control); 50% Ar–20% nitrogen–30% oxygen (Ar 50%); and 70% Ar–30% oxygen (Ar 70%). Hemodynamic parameters and myocardial function were monitored and serial blood samples taken. Pigs were observed up to 96 hours for survival and neurological recovery. Heart and brain were harvested for histopathology. Ten animals in each group were successfully resuscitated. Ninety‐six‐hour survival was 60%, 70%, and 90%, for the control, Ar 50%, and Ar 70% groups, respectively. In the Ar 50% and Ar 70% groups, 60% and 80%, respectively, achieved good neurological recovery, in contrast to only 30% in the control group (P<0.0001). Histology showed less neuronal degeneration in the cortex (P<0.05) but not in the hippocampus, and less reactive microglia activation in the hippocampus (P=0.007), after Ar compared with control treatment. A lower increase in circulating biomarkers of brain injury, together with less kynurenine pathway activation (P<0.05), were present in Ar‐treated animals compared with controls. Ar 70% pigs also had complete left ventricular function recovery and smaller infarct and cardiac troponin release (P<0.01). Conclusions Post‐resuscitation ventilation with Ar significantly improves neurologic recovery and ameliorates brain injury after cardiac arrest with long no‐flow duration. Benefits are greater after Ar 70% than Ar 50%.
Parametrizing the Conditionally Gaussian Prior Model for Source Localization with Reference to the P20/N20 Component of Median Nerve SEP/SEF

In this article, we focused on developing the conditionally Gaussian hierarchical Bayesian model (CG-HBM), which forms a superclass of several inversion methods for source localization of brain activity using somatosensory evoked potential (SEP) and field (SEF) measurements. The goal of this proof-of-concept study was to improve the applicability of the CG-HBM as a superclass by proposing a robust approach for the parametrization of focal source scenarios. We aimed at a parametrization that is invariant with respect to altering the noise level and the source space size. The posterior difference between the gamma and inverse gamma hyperprior was minimized by optimizing the shape parameter, while a suitable range for the scale parameter can be obtained via the prior-over-measurement signal-to-noise ratio, which we introduce as a new concept in this study. In the source localization experiments, the primary generator of the P20/N20 component was detected in the Brodmann area 3b using the CG-HBM approach and a parameter range derived from the existing knowledge of the Tikhonov-regularized minimum norm estimate, i.e., the classical Gaussian prior model. Moreover, it seems that the detection of deep thalamic activity simultaneously with the P20/N20 component with the gamma hyperprior can be enhanced while using a close-to-optimal shape parameter value.
Computer-based identification of potential compounds from Salviae miltiorrhizae against Neirisaral adhesion A regulatory protein

Abstract In silico studies are attracting considerable interest due to their ability to understand protein–ligand interactions at the atomic level. The main principal tools of this in silico analyses are molecular docking and molecular dynamic (MD) simulation. This paper examines how can natural compounds that are derived from Salviae miltiorrhizae to block Neisseria adhesion A Regulatory protein (NadR). In molecular docking analysis, only four compounds were found in higher binding affinity with NadR among 10 candidates (tanshinol B, tanshinol A, lithospermic acid and tournefolal were −7.61, −7.56, −8.22 and −7.81 kcal/mol, respectively, compared to −7.23 kcal/mol of native ligand). Absorption, distribution, metabolism, excretion (ADME) and toxicity properties, medicinal chemistry profile, and physicochemical features were displayed that tournefolal contains good properties to work as a safe and good anti-adhesive drug. Therefore, the complexes of these four ligands with NadR protein were subjected to 100 ns of MD simulation. RMSD, RMSF, RG and hydrogen bonding exhibited that tournefolal showed stable binding affinity and molecular interaction with NadR protein. In light of these results, there is now a need to conduct much more in vitro and in vivo studies about the efficacy of tournefolal. Communicated by Ramaswamy H. Sarma
Stability analysis of stochastic linear MPC with correlated disturbances

Internship subject: Model Predictive Control is nowadays a mature control technique whose popularity mostly relies in its capability of dealing with constraints and of ensuring performance optimization and in its suitability for practical application, by guaranteeing, at the same time, desirable stability properties. The inherent focus on the control real implementation led to focus on the effects of model uncertainties, disturbances and noises on the control performances and stability, yielding to robust formulations of MPC. If in the ﬁrst years many of the researchers efforts have been devoted to the robust formulation under worst-case assumptions on the uncertainties, last years saw a shift of the interest to stochastic MPC (SMPC), [3, 7, 6]. SMPC, in fact, permits to take into account the stochastic nature of the uncertainties, exploiting the knowledge of their distribution
Aspects of charge recombination and charge transport in organic solar cells and light-emitting devices

In this thesis, aspects of charge reconbination and charge trans)ort in organic solar cells and light-emitting devices are presented. These devices show promise relative to traditional inorganic semiconductors. We show that the energy splitting between singlet and triplet CT states in organic materials is appreciable and is material and geometry dependent. This prediction is used to guide the development of an OLED with enhanced fluorescence. The effects of nuclear disorder on optical and transport properties in organic semiconductors are examined and a general computational method for carryino out this analysis is described. The function of organic semiconductors is characterized by the interplay between localized and delocalized excited states. We present an ab initio method for obtaining the electronic coupling between CT states and excitons and (liscuss the nonadiabatic transitions between these states. Thesis Supervisor: Troy Van V'oorhis Title: Associate Professor of Chemistry
Look Before You Answer: Separating Answerability Prediction in QA Systems Intro2IE course mid-term report

In this project, we are tackling the problem of extractive reading comprehension (RC) where answers may or may not be in the paragraph. We start with QANet (Yu et al., 2018) as our starting model and implement some of the existing modiﬁcation to handle the case when the question can not be answered as baselines. We summarize the results of our baselines and discuss further direction.
Depicting HIV-1 Transcriptional Mechanisms: A Summary of What We Know

Despite the introduction of combinatory antiretroviral therapy (cART), HIV-1 infection cannot be cured and is still one of the major health issues worldwide. Indeed, as soon as cART is interrupted, a rapid rebound of viremia is observed. The establishment of viral latency and the persistence of the virus in cellular reservoirs constitute the main barrier to HIV eradication. For this reason, new therapeutic approaches have emerged to purge or restrain the HIV-1 reservoirs in order to cure infected patients. However, the viral latency is a multifactorial process that depends on various cellular mechanisms. Since these new therapies mainly target viral transcription, their development requires a detailed and precise understanding of the regulatory mechanism underlying HIV-1 transcription. In this review, we discuss the complex molecular transcriptional network regulating HIV-1 gene expression by focusing on the involvement of host cell factors that could be used as potential drug targets to design new therapeutic strategies and, to a larger extent, to reach an HIV-1 functional cure.
Distinct subcellular localization in the cytosol and apicoplast, unexpected dimerization and inhibition of Plasmodium falciparum glyoxalases

The ubiquitous glyoxalase system removes methylglyoxal as a harmful by‐product of glycolysis. Because malaria parasites have drastically increased glycolytic fluxes, they could be highly susceptible to the inhibition of this detoxification pathway. Here we analysed the intracellular localization, oligomerization and inhibition of the glyoxalases from Plasmodium falciparum. Glyoxalase I (GloI) and one of the two glyoxalases II (cGloII) were located in the cytosol of the blood stages. The second glyoxalase II (tGloII) was detected in the apicoplast pointing to alternative metabolic pathways. Using a variety of methods, cGloII was found to exist in a monomer–dimer equilibrium that might have been overlooked for homologues from other organisms and that could be of physiological importance. The compounds methyl‐gerfelin and curcumin, which were previously shown to inhibit mammalian GloI, also inhibited P. falciparum GloI. Inhibition patterns were predominantly competitive but were complicated because of the two different active sites of the enzyme. This effect was neglected in previous inhibition studies of monomeric glyoxalases I, with consequences for the interpretation of inhibition constants. In summary, the present work reveals novel general glyoxalase properties that future research can build on and provides a significant advance in characterizing the glyoxalase system from P. falciparum.
Discovery of an operon that participates in agmatine metabolism and regulates biofilm formation in Pseudomonas aeruginosa

Agmatine is the decarboxylation product of arginine and a number of bacteria have devoted enzymatic pathways for its metabolism. Pseudomonas aeruginosa harbours the aguBA operon that metabolizes agmatine to putrescine, which can be subsequently converted into other polyamines or shunted into the TCA cycle for energy production. We discovered an alternate agmatine operon in the P. aeruginosa strain PA14 named agu2ABCA′ that contains two genes for agmatine deiminases (agu2A and agu2A′). This operon was found to be present in 25% of clinical P. aeruginosa isolates. Agu2A′ contains a twin‐arginine translocation signal at its N‐terminus and site‐directed mutagenesis and cell fractionation experiments confirmed this protein is secreted to the periplasm. Analysis of the agu2ABCA′ promoter demonstrates that agmatine induces expression of the operon during the stationary phase of growth and during biofilm growth and agu2ABCA′ provides only weak complementation of aguBA, which is induced during log phase. Biofilm assays of mutants of all three agmatine deiminase genes in PA14 revealed that deletion of agu2ABCA′, specifically its secreted product Agu2A′, reduces biofilm production of PA14 following addition of exogenous agmatine. Together, these findings reveal a novel role for the agu2ABCA′ operon in the biofilm development of P. aeruginosa.
The pleiotropic role of transcription factor STAT3 in oncogenesis and its targeting through natural products for cancer prevention and therapy

Signal transducer and activator of transcription 3 (STAT3) is one of the crucial transcription factors, responsible for regulating cellular proliferation, cellular differentiation, migration, programmed cell death, inflammatory response, angiogenesis, and immune activation. In this review, we have discussed the classical regulation of STAT3 via diverse growth factors, cytokines, G‐protein‐coupled receptors, as well as toll‐like receptors. We have also highlighted the potential role of noncoding RNAs in regulating STAT3 signaling. However, the deregulation of STAT3 signaling has been found to be associated with the initiation and progression of both solid and hematological malignancies. Additionally, hyperactivation of STAT3 signaling can maintain the cancer stem cell phenotype by modulating the tumor microenvironment, cellular metabolism, and immune responses to favor drug resistance and metastasis. Finally, we have also discussed several plausible ways to target oncogenic STAT3 signaling using various small molecules derived from natural products.
Structural Basis for Binding of Plasmodium falciparum Erythrocyte Membrane Protein 1 to Chondroitin Sulfate and Placental Tissue and the Influence of Protein Polymorphisms on Binding Specificity*

Chondroitin sulfate (CS) A is a key receptor for adhesion of Plasmodium falciparum-infected erythrocytes (IEs) in the placenta and can also mediate adhesion to microvascular endothelial cells. IEs that adhere to CSA express var2csa-type genes, which encode specific variants of the IE surface antigen P. falciparum erythrocyte membrane protein 1 (PfEMP1). We report direct binding of native PfEMP1, isolated from IEs and encoded by var2csa, to immobilized CSA. Binding of PfEMP1 was dependent on 4-O-sulfated disaccharides and glucuronic acid rather than iduronic acid, consistent with the specificity of intact IEs. Using immobilized CS oligosaccharides as neoglycolipid probes, the minimum chain length for direct binding of PfEMP1 was eight monosaccharide units. Similarly for IE adhesion to placental tissue there was a requirement for 4-O-sulfated GalNAc and glucuronic acid mixed with non-sulfated disaccharides; 6-O-sulfation interfered with the interaction between placental CSA and IEs. The minimum chain length for maximal inhibition of adhesion was 10 monosaccharide residues. Partially 4-O-sulfated CS oligosaccharides (45–55% sulfation) were highly effective inhibitors of placental adhesion (IC50, 0.15 μg/ml) and may have potential for therapeutic development. We used defined P. falciparum isolates expressing different variants of var2csa in adhesion assays and found that there were isolate-specific differences in the preferred structural motifs for adhesion to CSA that correlated with polymorphisms in PfEMP1 encoded by var2csa-type genes. This may influence sites of IE sequestration or parasite virulence. These findings have significant implications for understanding the pathogenesis and biology of malaria, particularly during pregnancy, and the development of targeted interventions.
Gesundheit und Lebenszufriedenheit bei Erwerbsminderungsrentnern und -rentnerinnen: Die Bedeutung von finanziellen Ressourcen und Einsamkeit

Zusammenfassung Ziel der Studie Erwerbsminderungsrentner1 sind durch geringe finanzielle Ressourcen und einen schlechten Gesundheitszustand dem Risiko von weiteren gravierenden Einschränkungen ausgesetzt: Es drohen reduzierte Teilhabe, Einsamkeit und verminderte Lebenszufriedenheit. In der vorliegenden Arbeit wurden daher Zusammenhänge zwischen der Anzahl der Erkrankungen, selbstberichtetem Haushaltseinkommen (zur Verfügung stehende finanzielle Ressourcen) und Haushaltsauskommen (Auskommen mit dem Einkommen, d. h. kognitive und emotionale Bewertung der finanziellen Ressourcen), Einsamkeit und Lebenszufriedenheit untersucht. Methodik 199 befristete Erwerbsminderungsberentete wurden mittels strukturierter telefonischer Interviews zu 2 Messzeitpunkten (T1; T2=T1+ ca. 8 Monate) befragt. Ergebnisse Die wahrgenommene Einsamkeit und die Lebenszufriedenheit von Erwerbsminderungsrentnern stehen nicht im Zusammenhang mit der finanziellen Situation (Haushaltseinkommen). Hingegen hängt eine stärker wahrgenommene Einsamkeit mit niedrigeren wahrgenommenen finanziellen Ressourcen (Haushaltsauskommen) zusammen. Diese gehen wiederum mit einer geringeren Lebenszufriedenheit einher. Einsamkeit spielt eine vermittelnde Rolle dabei. Je schlechter der Gesundheitszustand, desto höher war auch die Einsamkeit und desto geringer die Lebenszufriedenheit. Schlussfolgerung Spezifische Rehabilitationsmaßnahmen für Erwerbsminderungsrentner sollten in besonderer Weise auf negative Wahrnehmungs- und Bewertungsprozesse bezüglich der subjektiven finanziellen Situation, des Erlebens von Einsamkeit und der Lebenszufriedenheit ausgerichtet werden. Angebote, die das Auskommen mit dem zur Verfügung stehenden Geld unterstützen und darauf abzielen, Einsamkeit zu überwinden und die Teilhabe zu verbessern, könnten helfen, die Lebenszufriedenheit von Erwerbsminderungsrentnern zu verbessern. Dies ist zentral, da andere Studien einen Zusammenhang zwischen Lebenszufriedenheit und der Rückkehr ins Arbeitsleben sowie sozialer Teilhabe gezeigt haben.
Struvite Formation in Wastewater Treatment Plants: Opportunities for Nutrient Recovery

Nutrient removal from wastewater discharges is an increasing challenge for water authorities, as regulatory authorities tighten discharge standards to avoid eutrophication problems in receiving waters. Significant costs are associated with the extra treatment processes required to meet these new discharge standards. The most widely used technologies for nutrient removal include biological nitrification/denitrification for nitrogen removal and metal salt precipitation for phosphorus removal. Both approaches result in the nutrient being made unrecoverable for possible use as a fertiliser. An alternative to these conventional technologies which can provide for recovery of the nutrient as a commercial fertiliser could be the production of magnesium ammonium phosphate (struvite).
Deep learning‐assisted magnetic resonance imaging prediction of tumor response to chemotherapy in patients with colorectal liver metastases

Accurate evaluation of tumor response to preoperative chemotherapy is crucial for assigning appropriate patients with colorectal liver metastases (CRLM) to surgery or conservative therapy. However, there is no well‐recognized method for predicting pathological response before surgery. Our study constructed and validated a deep learning algorithm using prechemotherapy and postchemotherapy magnetic resonance imaging (MRI) to predict pathological response in CRLM. CRLM patients from center one who had ≤5 lesions and were scheduled to receive preoperative chemotherapy followed by liver resection between January 2013 and November 2016, were included prospectively and chronologically divided into a training cohort (80% of patients) and a testing cohort (20% of patients). Patients from center two were included January 2017 and December 2018 as an external validation cohort. MRI‐based models were constructed to discriminate according to pathology tumor regression grade (TRG) between the response (TRG1/2) and nonresponse (TRG3/4/5) groups at the lesion level. From center one, 155 patients (328 lesions) were included; chronologically, 101 (264 lesions) in the training cohort and 54 (64 lesions) in the testing cohort. The model achieved better accuracy (0.875 vs 0.578) and AUC (0.849 vs 0.615) than RECIST for discriminating response; it also distinguished the survival outcomes after hepatectomy better than the RECIST criteria. Evaluations of the external validation cohort (25 patients, 61 lesions) also showed good ability with an AUC of 0.833. In conclusion, the MRI‐based deep learning model provided accurate prediction of pathological tumor response to preoperative chemotherapy in patients with CRLM and may inform individualized treatment.