Miracle-dz/UniFAR-FTUs huggingface dataset:
Systemic Administration of Avian Defensin 7: Distribution, Cellular Target, and Antibacterial Potential in Mice

Defensins are natural antimicrobial peptides. The avian beta-defensin AvBD7 isolated from the chicken bone marrow possess broad antibacterial spectrum and strong resistance to proteolysis. However, its ability to fight systemic infections of major concern for public health, such as salmonellosis, is unknown. As a first approach, fluorescence labeling of AvBD7 allowed to track its systemic distribution after intraperitoneal injection in mice using whole body live imaging. It was associated to peritoneal cells and to deeper organs such as the liver. In the next step, the use of labeled AvBD7 allowed to observe its interaction with murine macrophages in culture. After incubation, it was able to penetrate inside the cells through an endocytosis-like mechanism. Furthermore, natural AvBD7 contributed to the control of intracellular multiplication of a multidrug resistant Salmonella strain, after incubation with infected macrophages. Finally, administration in a model of systemic lethal Salmonella infection in mice led to significant improvement of mouse survival, consistently with significant reduction of the liver bacterial load. In conclusion, the results reveal a hitherto unknown intracellular antibacterial effect of AvBD7 in Salmonella target cells and support AvBD7 as a candidate of interest for the treatment of infectious diseases caused by multidrug-resistant pathogenic Enterobacteriaceae.
Prognostic significance of serum soluble DR5 levels in small-cell lung cancer

The death receptor 5 (DR5) is a member of the tumor necrosis factor receptor superfamily that can transduce the apoptosis signal in cells. This study assessed serum levels of soluble death receptor 5 (sDR5) in small-cell lung cancer (SCLC) patients compared with those in healthy controls. Clinicopathological features of patients, treatment responses, and overall survival of patients were also recorded and analyzed. The sDR5 levels were analyzed using ELISA in 50 healthy controls and 82 SCLC patients before and after first-line chemotherapy. The statistical data showed that pre-treatment levels of serum sDR5 in SCLC patients were higher than those of healthy controls (P<0.001). Pre-treatment levels of serum sDR5 were significantly associated with smoking history of patients, Veterans Administration Lung Study Group (VALSG) stage, tumor size, and lymph node (N) metastasis (P=0.028, 0.001, 0.028, and 0.01, respectively). After treatment with the first-line chemotherapy, the post-treatment levels of serum sDR5 were obviously decreased (P<0.001), and correlated with treatment responses (P<0.001), although there was no significant difference in their pretreatment sDR5 levels (P=0.62). Cox proportional hazard analysis demonstrated that the post-treatment levels of serum sDR5, VALSG stage, and PS status were all independent predictors for overall survival of patients. The results from the current study indicate that serum level of sDR5 could be further confirmed as a biomarker to predict treatment responses and survival of SCLC patients.
Podoplanin Positive Myeloid Cells Promote Glioma Development by Immune Suppression

The dynamic and interactive tumor microenvironment is conceived as a considerable parameter in tumor development and therapy response. Implementing this knowledge in the development of future cancer treatments could provide novel options in the combat of highly aggressive and difficult-to-treat tumors such as gliomas. One compartment of the tumor microenvironment that has gained growing interest is the immune system. As endogenous defense machinery the immune system has the capacity to fight against cancer cells. This, however, is frequently circumvented by tumor cells engaging immune-regulatory mechanisms that disable tumor-directed immune responses. Thus, in order to unlock the immune system against cancer cells, it is crucial to characterize in great detail individual tumor-associated immune cell subpopulations and dissect whether and how they influence immune evasion. In this study we investigated the function of a tumor-associated myeloid cell subpopulation characterized by podoplanin expression on the development of high-grade glioma tumors. Here, we show that the deletion of podoplanin in myeloid cells results in increased (CD8+) T-cell infiltrates and significantly prolonged survival in an orthotopic transplantation model. In vitro co-cultivation experiments indicate a podoplanin-dependent transcriptional regulation of arginase-1, a well-known player in myeloid cell-mediated immune suppression. These findings identify podoplanin positive myeloid cells as one novel mediator of the glioma-induced immune suppression. Thus, the targeted ablation of podoplanin positive myeloid cells could be included in combinatorial cancer therapies to enhance immune-mediated tumor elimination.
Identification of Phage Viral Proteins With Hybrid Sequence Features

The uniqueness of bacteriophages plays an important role in bioinformatics research. In real applications, the function of the bacteriophage virion proteins is the main area of interest. Therefore, it is very important to classify bacteriophage virion proteins and non-phage virion proteins accurately. Extracting comprehensive and effective sequence features from proteins plays a vital role in protein classification. In order to more fully represent protein information, this paper is more comprehensive and effective by combining the features extracted by the feature information representation algorithm based on sequence information (CCPA) and the feature representation algorithm based on sequence and structure information. After extracting features, the Max-Relevance-Max-Distance (MRMD) algorithm is used to select the optimal feature set with the strongest correlation between class labels and low redundancy between features. Given the randomness of the samples selected by the random forest classification algorithm and the randomness features for producing each node variable, a random forest method is employed to perform 10-fold cross-validation on the bacteriophage protein classification. The accuracy of this model is as high as 93.5% in the classification of phage proteins in this study. This study also found that, among the eight physicochemical properties considered, the charge property has the greatest impact on the classification of bacteriophage proteins These results indicate that the model discussed in this paper is an important tool in bacteriophage protein research.
Grading Standards, Student Ability and Errors in College Admission

Grades are important for admission of students in most higher education programs. Analyzing admission and student performance data at a major Norwegian business school, we find that the grading practice of teachers at regional colleges sending students to the school is affected by the average performance of the students being graded. Teachers at colleges recruiting good students from upper secondary school tend to be strict in their grading practice, while teachers at colleges recruiting less good students tend to follow a lenient practice. This has implications for the interpretation of grades and hence for optimal admission procedures. We develop a methodology to assess the consequences of differential grading standards. Approximately 10% of the students in our data are admitted at the expense of more competent students. We demonstrate costs for the school admitting the wrong students and in particular for the rejected students.
A Study of the Mechanism of the Congruence of Leader–Follower Power Distance Orientation on Employees’ Task Performance

Based on implicit leadership theory, we examine the congruence effect of leader–follower power distance orientation (PDO) on follower trust in supervisor and work engagement, which in turn influences employees’ task performance. Results of polynomial regressions on 526 dyads supported the congruence effect hypothesis. The results show that (1) the congruence of leader–follower PDO leads to better performance; (2) under the condition of congruence, subordinate task performance is higher when leader–follower PDO matching in low–low ratings congruence than it is in high–high ratings congruence; (3) under the condition of asymmetrical incongruence, the follower had higher task performance when a leader’s PDO is lower than a follower’s PDO; (4) trust in supervisor and the work engagement mediate the effect of congruence of leader–follower PDO on employees’ task performance; (5) trust in supervisor also mediates the effect of congruence of leader–follower PDO on employees’ work engagement.
Meta-Network Analysis of Structural Correlation Networks Provides Insights Into Brain Network Development

Analysis of developmental brain networks is fundamentally important for basic developmental neuroscience. In this paper, we focus on the temporally-covarying connection patterns, called meta-networks, and develop a new mathematical model for meta-network decomposition. With the proposed model, we decompose the developmental structural correlation networks of cortical thickness into five meta-networks. Each meta-network exhibits a distinctive spatial connection pattern, and its covarying trajectory highlights the temporal contribution of the meta-network along development. Systematic analysis of the meta-networks and covarying trajectories provides insights into three important aspects of brain network development.
Effect of Load on Vibrations of a Railway Gearbox

Condition monitoring of a railway gearbox installed on a metro vehicle is described. The peculiarities of the application, which led to a sort of “bouncing” of the whole gearbox when running in coasting at high speed, are such that extensive failures of the cage of a taper roller bearing were observed and related to the abnormal accelerations measured on the casing. The complexity of the signals led to the need to use numerical indicators more sophisticated than levels or energy. A proper combination of different indicators was checked during tests in different conditions and verified through the application of the procedure to signals from regular service. A combination of energy and kurtosis was found to give the best results in terms of reliability of detection.
Dose-Dependent Effects of Aloin on the Intestinal Bacterial Community Structure, Short Chain Fatty Acids Metabolism and Intestinal Epithelial Cell Permeability

Aloe leaf or purified aloin products possess numerous therapeutic and pharmaceutical properties. It is widely used as ingredients in a variety of food, cosmetic and pharmaceutical products. Animal studies have shown that consumption of aloe or purified aloin cause intestinal goblet cell hyperplasia, and malignancy. Here, we tested antibacterial effects of aloin, against intestinal commensal microbiota. Minimum inhibitory concentration of aloin for several human commensal bacterial species (Gram-positive and Gram-negative) ranged from 1 to 4 mg/ml. Metabolism studies indicated that Enterococcus faecium was capable of degrading aloin into aloe-emodin at a slower-rate compared to Eubacterium spp. As a proof of concept, we incubated 3% rat fecal-slurry (an in vitro model to simulate human colon content) with 0.5, 1, and 2 mg/ml of aloin to test antimicrobial properties. Low aloin concentrations showed minor perturbations to intestinal bacteria, whereas high concentration increased Lactobacillus sp. counts. Aloin also decreased butyrate-production in fecal microbiota in a dose-dependent manner after 24 h exposure. The 16S rRNA sequence-data revealed that aloin decreases the abundance of butyrate-producing bacterial species. Transepithelial resistant result revealed that aloin alters the intestinal barrier-function at higher concentrations (500 μM). In conclusion, aloin exhibits antibacterial property for certain commensal bacteria and decreases butyrate-production in a dose -dependent manner. HIGHLIGHTS –Aloin exhibits antibacterial properties for certain intestinal commensal bacteria. –In rat fecal slurry (an in vitro model to simulate human colon content), longer aloin exposure (24 h) decreases the butyrate production in dose dependent manner. –The 16s rRNA sequencing data show that aloin decreased the abundance of butyrate producing bacterial species. –Rat intestinal commensal bacteria metabolized aloin into aloe-emodin. –Aloin altered the intestinal epithelial cells barrier integrity, however, the metabolic product of aloin - Aloe-emodin did not alter epithelial cells permeability.
Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors

Influenza A virus (IAV) matrix protein 2 (M2), an ion channel, is crucial for virus infection, and therefore, an important anti-influenza drug target. Adamantanes, also known as M2 channel blockers, are one of the two classes of Food and Drug Administration-approved anti-influenza drugs, although their use was discontinued due to prevalent drug resistance. Fast emergence of resistance to current anti-influenza drugs have raised an urgent need for developing new anti-influenza drugs against resistant forms of circulating viruses. Here we propose a simple theoretical criterion for fast virtual screening of molecular libraries for candidate anti-influenza ion channel inhibitors both for wild type and adamantane-resistant influenza A viruses. After in silico screening of drug space using the EIIP/AQVN filter and further filtering of drugs by ligand based virtual screening and molecular docking we propose the best candidate drugs as potential dual inhibitors of wild type and adamantane-resistant influenza A viruses. Finally, guanethidine, the best ranked drug selected from ligand-based virtual screening, was experimentally tested. The experimental results show measurable anti-influenza activity of guanethidine in cell culture.
Compound Mixed Poisson Distributions II

The concept of compound mixed Poisson distributions in actuarial science is used to represent such variables as the total amount of claims or losses payable by an insurer. This paper provides the second part of the list of approximate forms for the compound mixed Poisson distribution (following up from Nadarajah and Kotz (2006)). The calculations involve use of several special functions and their properties. We believe that the results will serve as an important reference in actuarial science.
Enhanced equity-credit modelling for contingent convertibles

Contingent convertible (CoCo) bonds are characterized by forced equity conversion under either an accounting or regulatory trigger. The accounting trigger occurs when the capital ratio of the issuing bank falls below some contractual threshold. Under the regulatory trigger, sometimes called the point-of-non-viability (PONV) trigger, the regulatory authority may enforce equity conversion when the financial health of the bank deteriorates to certain distressed level. In this paper, we propose an equity-credit modelling of the joint process of the stock price and the capital ratio that integrates both a structural approach for the accounting trigger and a reduced-form approach for the PONV trigger of equity conversion. We also construct effective Fortet algorithms and finite difference schemes for numerical pricing of CoCo bonds under various forms of equity conversion pay-off. The pricing properties of CoCo bonds are examined under different assumptions for the state-dependent intensity of the PONV trigger, the contractual specifications and market conditions.
Plasma alpha‐synuclein detected by single molecule array is increased in PD

We utilized ultrasensitive single molecule technology to measure plasma alpha‐synuclein in 221 subjects (51 controls, 170 PD). Plasma alpha‐synuclein levels were significantly higher in PD than controls (15506.3 vs. 13057.0 pg/mL, P = 0.037), adjusting for age and gender. In PD, alpha‐synuclein levels did not vary by H&Y stage or UPDRS motor scores but were significantly higher in PD patients with poorer cognition (MMSE ≤ 25) than controls (P = 0.016, Bonferroni corrected P = 0.047). Alpha‐synuclein levels quantified using ultrasensitive single molecule technology discriminate PD from controls and correlate with cognitive severity. These preliminary findings require independent validation to determine the utility of this assay.
Using Growth and Transpiration Phenotyping Under Controlled Conditions to Select Water Efficient Banana Genotypes

Water deficit is one of the world’s major constraints in agriculture and will aggravate in the future. Banana (Musa spp.) is an important crop that needs vast amounts of water for optimal production. The International Transit Center of Bioversity International holds the world’s biggest collection of banana biodiversity (>1,500 accessions). The long-term aim of this research is to evaluate the potential within this collection for climate smart agricultural usage. Therefore, we developed a phenotyping setup under controlled environmental conditions and we selected 32 representatives of the Musa biodiversity (29 cultivars and 3 wild relatives) for evaluation. The best performing genotypes accumulated six to seven times more biomass than the least performing. Eight genotypes (five ABB, one AAB, and two AAA) invest under osmotic stress significantly more in root growth than in leaf growth. We predict therefore that these genotypes have potential for high productivity under rain fed conditions with a short dry season. To gain more insight in the transpiration physiology, we gravimetrically monitored individual plant transpiration over the diurnal period. All analyzed genotypes showed a marked reduction in transpiration rate in the afternoon. Moreover, the timing of this onset, as well as its impact on total transpiration, was genotype dependent. This phenomenon was more pronounced in 13 genotypes (eight ABB, two AAB, two AA, one BB). Banana is a crop originating from the humid tropics and has developed a strong root pressure to maintain an efficient water and nutrient transport even under saturated relative humidity conditions. Therefore, we hypothesize that the diurnal transpiration decline contributes to a higher water use efficiency without compromising the nutrient transport. Of the eight genotypes that had the best growth under osmotic stress, all analyzed ABB cultivars have a lower maximal transpiration rate, keep this maximal transpiration for a shorter time and therefore consume less water per day. We conclude that lab models are very useful to study the biodiversity and to identify different traits that contribute to a better drought tolerance/avoidance. We encourage researchers investigating other crops to start exploring their collections.
The Human Behaviour-Change Project: An artificial intelligence system to answer questions about changing behaviour

Changing behaviour is necessary to address many of the threats facing human populations. However, identifying behaviour change interventions likely to be effective in particular contexts as a basis for improving them presents a major challenge. The Human Behaviour-Change Project harnesses the power of artificial intelligence and behavioural science to organise global evidence about behaviour change to predict outcomes in common and unknown behaviour change scenarios.
Designing and Characterization of a Novel Delivery System for Improved Cellular Uptake by Brain Using Dendronised Apo-E-Derived Peptide

Neurodegenerative diseases (ND) are characterized by the progressive loss of neuronal structure or function mostly associated with neuronal death. The presence of the blood–brain barrier (BBB) is considered the main obstacle that prevents the penetration of almost all drugs rendering the diseases untreatable. Currently, one of the most promising approaches for drug delivery to the brain is by employing endogenous transcytosis to improve endothelial cell uptake. This study aimed to exploit this potential route of enhanced drug uptake through the design and characterization of low generations lysine dendrons with further functionalization of dendron with ApoE-derived peptide (AEP) ligand to improve cellular uptake and targeting of delivery to the brain. Dendrons and peptide were synthesized using solid phase peptide chemistry and the products were characterized by mass spectrometry and high performance liquid chromatography which confirmed the successful synthesis of dendrons and functionalization with the AEP. Cell viability and lactate dehydrogenase release were conducted to study the cytotoxicity of the materials against an immortalized brain endothelial cell line (bEnd.3) which demonstrated that no toxicity was seen at the concentration range used (up to 400 μM) for up to 48 h incubation. Cellular uptake of the synthesized molecules was examined using confocal microscopy and flow cytometer which clearly showed the cellular uptake of the dendronised carrier systems and that the highest percentage of cellular uptake was achieved with the AEP-functionalized dendron. This study has therefore demonstrated the successful synthesis of dendronised carrier systems with the potential to act as carriers for improved delivery and targeting the brain.
Optimizing the Management and Outcomes of Failed Back Surgery Syndrome: A Consensus Statement on Definition and Outlines for Patient Assessment

Failed back surgery syndrome (FBSS) is a controversial term for identifying patients affected by new, recurrent, or persistent pain in the low back and/or legs following spinal surgery. The lack of a comprehensive standardized care pathway compromises the appropriate management of FBSS patients, which is associated with a heavy financial burden. An international panel of spine surgeons, neurosurgeons, and pain specialists with a particular interest in FBSS established the chronic back and leg pain (CBLP) network with the aim of addressing the challenges and barriers in the clinical management of FBSS patients by building a common transdisciplinary vision. Based on literature reviews, additional input from clinical expertise of multiple professional disciplines, and consensus among its members, the network attempted to provide recommendations on the management of patients with FBSS utilizing a multidisciplinary team (MDT) approach. The presentation of this work has been divided in two separate parts to enhance its clarity. This first paper, in favour of selecting appropriate validated tools to improve the FBSS patient assessment, focuses on FBSS taxonomy and its clinical implications for evaluation. Concise recommendations for assessment, treatment, and outcome evaluation using a MDT approach would be an important resource for specialists and nonspecialist clinicians who manage patients with FBSS, to improve decision-making, reduce variation in practice, and optimize treatment outcomes in this difficult-to-treat population.