Miracle-dz/UniFAR-FTUs huggingface dataset:
Online Learning with Abstention

We present an extensive study of the key problem of online learning where algorithms are allowed to abstain from making predictions. In the adversarial setting, we show how existing online algorithms and guarantees can be adapted to this problem. In the stochastic setting, we first point out a bias problem that limits the straightforward extension of algorithms such as UCB-N to time-varying feedback graphs, as needed in this context. Next, we give a new algorithm, UCB-GT, that exploits historical data and is adapted to time-varying feedback graphs. We show that this algorithm benefits from more favorable regret guarantees than a possible, but limited, extension of UCB-N. We further report the results of a series of experiments demonstrating that UCB-GT largely outperforms that extension of UCB-N, as well as more standard baselines.
A study on temporal segmentation strategies for extracting common spatial patterns for brain computer interfacing

Brain computer interfaces (BCI) create a new approach to human computer communication, allowing the user to control a system simply by performing mental tasks such as motor imagery. This paper proposes and analyses different strategies for time segmentation in extracting common spatial patterns of the brain signals associated to these tasks leading to an improvement of BCI performance. I. I NTRODUCTION
Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate

Mutations in the glucocerebrosidase 1 (GBA1) gene are related to both Parkinson disease (PD) and Gaucher disease (GD). In both cases, the condition is associated with deficiency of glucocerebrosidase (GCase), the enzyme encoded by GBA1. Ambroxol is a small molecule chaperone that has been shown in mice to cross the blood‐brain barrier, increase GCase activity and reduce alpha‐synuclein protein levels. In this study, we analyze the effect of ambroxol treatment on GCase activity in healthy nonhuman primates. We show that daily administration of ambroxol results in increased brain GCase activity. Our work further indicates that ambroxol should be investigated as a novel therapy for both PD and neuronopathic GD in humans.
To Belong Is to Matter

In four methodologically diverse studies (N = 644), we found correlational (Study 1), longitudinal (Study 2), and experimental (Studies 3 and 4) evidence that a sense of belonging predicts how meaningful life is perceived to be. In Study 1 (n = 126), we found a strong positive correlation between sense of belonging and meaningfulness. In Study 2 (n = 248), we found that initial levels of sense of belonging predicted perceived meaningfulness of life, obtained 3 weeks later. Furthermore, initial sense of belonging predicted independent evaluations of participants essays on meaning in life. In Studies 3 (n = 105) and 4 (n = 165), we primed participants with belongingness, social support, or social value and found that those primed with belongingness (Study 3) or who increased in belongingness (Study 4) reported the highest levels of perceived meaning. In Study 4, belonging mediated the relationship between experimental condition and meaning.
Macrocyclic θ-defensins suppress tumor necrosis factor-α (TNF-α) shedding by inhibition of TNF-α–converting enzyme

Theta-defensins (θ-defensins) are macrocyclic peptides expressed exclusively in granulocytes and selected epithelia of Old World monkeys. They contribute to anti-pathogen host defense responses by directly killing a diverse range of microbes. Of note, θ-defensins also modulate microbe-induced inflammation by affecting the production of soluble tumor necrosis factor (sTNF) and other proinflammatory cytokines. Here, we report that natural rhesus macaque θ-defensin (RTD) isoforms regulate sTNF cellular release by inhibiting TNF-α–converting enzyme (TACE; also known as a disintegrin and metalloprotease 17; ADAM17), the primary pro-TNF sheddase. Dose-dependent inhibition of cellular TACE activity by RTDs occurred when leukocytes were stimulated with live Escherichia coli cells as well as numerous Toll-like receptor agonists. Moreover, the relative inhibitory potencies of the RTD isoforms strongly correlated with their suppression of TNF release by stimulated blood leukocytes and THP-1 monocytes. RTD isoforms also inhibited ADAM10, a sheddase closely related to TACE. TACE inhibition was abrogated by introducing a single opening in the RTD-1 backbone, demonstrating that the intact macrocycle is required for enzyme inhibition. Enzymologic analyses showed that RTD-1 is a fast binding, reversible, non-competitive inhibitor of TACE. We conclude that θ-defensin–mediated inhibition of pro-TNF proteolysis by TACE represents a rapid mechanism for the regulation of sTNF and TNF-dependent inflammatory pathways. Molecules with structural and functional features mimicking those of θ-defensins may have clinical utility as TACE inhibitors for managing TNF-driven diseases.
Trends and Determinants of Human Papillomavirus Concordance Among Human Immunodeficiency Virus–Positive and –Negative Heterosexual Couples in Rakai, Uganda

Background Limited data are available on human papillomavirus (HPV) infection among human immunodeficiency virus (HIV)-negative or HIV-positive couples followed longitudinally. Methods Genital HPV was assessed in 725 concordant HIV-negative couples and 209 HIV-positive couples enrolled in a male circumcision trial in Rakai, Uganda, using the Roche Linear Array assay, which detects 37 HPV genotypes. Human papillomavirus prevalence and determinants of genotype-specific concordance were assessed at annual visits. Cumulative detection of HPV genotypes over 2 years was also assessed. Results At enrollment, HPV infection was detected in 54% of HIV-negative women, 56% of HIV-negative men, and 93% of HIV-positive men and women. For HIV-negative couples, genotypic concordance was 30% at baseline (n = 219/725) and declined significantly with age (adjusted prevelance risk ratio [adjPRR] = 0.53; 95% confidence interval [CI] = 0.28-0.93 comparing women aged >40 years to those aged 15-19 years) and male circumcision (adjPRR = 0.60; 95% CI = 0.47-0.77) and increased among couples with recent intercourse (adjPRR = 1.26; 95% CI = 1.04-1.53). These associations were not seen in HIV-positive couples. Among couples with HPV results at all visits, ≥1 of the same genotypes were detected in both partners in 60% of HIV-negative couples and 96% of HIV-positive couples over 2 years. Conclusion Human papillomavirus genotype-specific concordance is more common in HIV-positive couples, and irrespective of HIV status, the majority of couples exhibit HPV concordance over 2 years.
Thrombectomy outcomes for acute stroke patients with anterior circulation tandem lesions: a clinical registry and an update of a systematic review with meta‐analysis

Although mechanical thrombectomy (MT) appears to be superior in stroke patients with extracranial carotid disease (ECD) compared to thrombolysis alone, the impact of emergent carotid stenting during MT remains unclear. The MT outcomes were assessed in anterior stroke patients with ECD, especially when combined with carotid stenting.
The pro-α1(V) collagen gene (Col5a1) is coordinately regulated by miR-29b with core promoter in cultured cells

ABSTRACT Aims: Col5a1 encodes the α1 chain of type V collagen, a quantitatively minor fibrillar collagen that is critical for the formation and function of the organs in the body. MicroRNAs (miRNAs) are small noncoding RNAs that posttranscriptionally regulate biological functions by binding to the 3ʹ-untranslated region (3ʹUTR) of specific target mRNA. In this study, we investigated the posttranscriptional regulation of miRNAs on the Col5a1 gene expression. Materials and Methods: We cultured osteoblasts and fibroblasts of cell lines. To examine the 3ʹUTR activity of the Col5a1 gene, chimeric plasmids constructs containing the core promoter and 3ʹUTR of Col5a1 were generated and luciferase assays were performed. We also evaluated the role of miRNA using constructs that were mutated at the putative binding sites of miRNA. In addition, we evaluated the endogenous mRNA and protein, and luciferase activity of the Col5a1 gene after miRNA overexpression/knockdown or CRISPR/Cas9-induced knockout. Results: The luciferase assay showed a decreased activity of the 3ʹUTR of Col5a1 gene. However, the expression of the mutant constructs of miRNA-binding sites was restored. The overexpression of miRNA inhibited the Col5a1 gene not only with regard to the luciferase activity and endogenous mRNA but also at the protein level. In contrast, the RNAi-mediated knockdown or CRISPR/Cas9 system increased the expression of the Col5a1 gene. Conclusion: These results provided evidence that miR-29b regulates the Col5a1 gene expression through binding to the 3ʹUTR, which might play an important role in the pathogenesis of disease related to bone metabolism and fibrogenic reactions.
Polyurethanes Crosslinked with Poly(vinyl alcohol) as a Slowly-Degradable and Hydrophilic Materials of Potential Use in Regenerative Medicine

Novel, slowly-degradable and hydrophilic materials with proper mechanical properties and surface characteristics are in great demand within the biomedical field. In this paper, the design, synthesis, and characterization of polyurethanes (PUR) crosslinked with poly(vinyl alcohol) (PVA) as a new proposition for regenerative medicine is described. PVA-crosslinked PURs were synthesized by a two-step polymerization performed in a solvent (dimethylsulfoxide, DMSO). The raw materials used for the synthesis of PVA-crosslinked PURs were poly(ε-caprolactone) (PCL), 1,6-hexamethylene diisocyanate (HDI), and PVA as a crosslinking agent. The obtained materials were studied towards their physicochemical, mechanical, and biological performance. The tests revealed contact angle of the materials surface between 38–47° and tensile strength in the range of 41–52 MPa. Mechanical characteristics of the obtained PURs was close to the characteristics of native human bone such as the cortical bone (TSb = 51–151 MPa) or the cancellous bone (TSb = 10–20 MPa). The obtained PVA-crosslinked PURs did not show significant progress of degradation after 3 months of incubation in a phosphate-buffered saline (PBS). Accordingly, the obtained materials may behave similar to slowly-degradable materials, which can provide long-term physical support in, for example, tissue regeneration, as well as providing a uniform calcium deposition on the material surface, which may influence, for example, bone restoration. A performed short-term hemocompatibility study showed that obtained PVA-crosslinked PURs do not significantly influence blood components, and a cytotoxicity test performed with the use of MG 63 cell line revealed the great cytocompatibility of the obtained materials. According to the performed studies, such PVA-crosslinked PURs may be a suitable proposition for the field of tissue engineering in regenerative medicine.
Tolerogenic Nanoparticles Induce Antigen-Specific Regulatory T Cells and Provide Therapeutic Efficacy and Transferrable Tolerance against Experimental Autoimmune Encephalomyelitis

T cells reacting to self-components can promote tissue damage when escaping tolerogenic control mechanisms which may result in autoimmune disease. The current treatments for these disorders are not antigen (Ag) specific and can compromise host immunity through chronic suppression. We have previously demonstrated that co-administration of encapsulated or free Ag with tolerogenic nanoparticles (tNPs) comprised of biodegradable polymers that encapsulate rapamycin are capable of inhibiting Ag-specific transgenic T cell proliferation and inducing Ag-specific regulatory T cells (Tregs). Here, we further show that tNPs can trigger the expansion of endogenous Tregs specific to a target Ag. The proportion of Ag-specific Treg to total Ag-specific T cells remains constant even after subsequent Ag challenge in combination with a potent TLR7/8 agonist or complete Freund’s adjuvant. tNP-treated mice do not develop experimental autoimmune encephalomyelitis (EAE) after adoptive transfer of encephalitogenic T cells; furthermore, tNP treatment provided therapeutic protection in relapsing EAE that was transferred to naïve animals. These findings describe a potent therapy to expand Ag-specific Tregs in vivo and suppress T cell-mediated autoimmunity.
Solution Refining for MOD-YBCO Optimization: An NMR Study

In this paper, a study of both pure and 5% BaZrO33-doped YBCO low-fluorine coating solutions performed by 1H-Nuclear Magnetic Resonance (NMR) spectroscopic techniques is presented. This investigation enabled us to unequivocally identify the chemical species involved in the solution aging process. It was found that the presence of traces of methanol, typically used for the preparation of the solutions, promoted methyl propionate formation. Since the methanol concentration reduction in time is not completely balanced by methyl propionate formation, it is supposed that additional esterification reactions involving other acids might occur. The presence of methyl propionate ester was not recognized in solutions obtained through a refining process in which residual methanol traces were fully removed. The modification in time of the solution composition was found to be in strong correlation with the degradation of the film properties for standard solution, whereas no degradation, in the same time frame, was observed for the films prepared with the refined solutions. Indeed, both YBCO and YBCO + 5% BaZrO3 films, grown with aged refined solutions, exhibit critical temperature values above 91 K and microstructure comparable with the ones recorded in samples obtained with freshly prepared solutions. Even though the exact role of the ester in the YBCO phase formation and film quality could not be identified yet, some possible mechanisms have been proposed and discussed.
Performance of pureline broiler breeders fed two levels of vitamin E.

Reported in this paper is an experiment designed to evaluate responses of two commercial broiler dam purelines (A and B) continuously fed 10 or 300 IU of vitamin E/kg from 168 to 441 d of age. Prior to Day 168, all pullets were fed diets containing 10 IU of vitamin E/kg. During the early laying period, percentage hen-day ovulations and percentage hen-day normal egg production were similar for both lines and diets. During the latter part of the laying cycle, there were differences between lines for these traits (A > B), as well as for BW and egg weight for which line differences were reversed (A < B). Also during this period, percentage hen-day ovulations and percentage hen-day normal egg production differed between diets (300 > 10 IU/kg). These differences between diets were consistent with the greater number of females that entered lay and higher hen-housed egg production of the 300- than 10-IU/kg group. Although during the laying cycle all females received a fixed amount of feed, BW gains were greater for Line B than A and for the 300- than the 10-IU/kg level of vitamin E. Heterophil (H):lymphocyte (L) ratios, percentage livability, and relative asymmetries of shank length and diameter were similar among groups. Pullets from Line B and those fed the higher level of vitamin E exhibited more fear than their counterparts. Head shaking did not differ between vitamin E levels; however, there was a line-by-time of day interaction for this behavior. The 30-fold difference in dietary vitamin E was reflected by a 15-fold difference in plasma vitamin E levels in both lines. For vitamin E level in the yolk, however, there was a line-by-diet interaction. The interaction resulted from no difference between lines at the 10 IU/kg level and differences of 10- and 6+-fold in Lines B and A at the 300 IU/ kg level, respectively. Overall, responses to continuous feeding of vitamin E at these levels were influenced by genetic stock, age, duration of feeding, and measurement criteria.
Novelty Detection Classifiers in Weed Mapping: Silybum marianum Detection on UAV Multispectral Images

In the present study, the detection and mapping of Silybum marianum (L.) Gaertn. weed using novelty detection classifiers is reported. A multispectral camera (green-red-NIR) on board a fixed wing unmanned aerial vehicle (UAV) was employed for obtaining high-resolution images. Four novelty detection classifiers were used to identify S. marianum between other vegetation in a field. The classifiers were One Class Support Vector Machine (OC-SVM), One Class Self-Organizing Maps (OC-SOM), Autoencoders and One Class Principal Component Analysis (OC-PCA). As input features to the novelty detection classifiers, the three spectral bands and texture were used. The S. marianum identification accuracy using OC-SVM reached an overall accuracy of 96%. The results show the feasibility of effective S. marianum mapping by means of novelty detection classifiers acting on multispectral UAV imagery.
Effect of Crumb Rubber Proportion on Compressive and Flexural Behavior of Concrete

The compressive and flexural behavior of crumb rubber concrete(CRC) was investigated with the content of crumb rubber ranging from 50/0 to 150/0 by volume.The cubic compressive strength and the stress-strain curve under uniaxial compression were measured and the flexural tensile strain was recorded using a dynamic strain indicator.The results show that the elastic modulus of CRC decreases noticeably,and the peak compressive strain can reach 4 106×10-6.The tensile strain curve exhibits a significant yield limit of CRC specimen.The ultimate tensile strain of the four-point bending test can reach 260×10-6—640×10-6.Those measured strain values are much greater than the controlled group,indicating that the ductility and the deformation of concrete can be greatly enhanced with the incorporation of crumb rubber.In addition,the data of cubic compressive strength for one-year age specimens shows CRC is steadily gaining later-strength.
Macrophage plasticity, polarization, and function in health and disease

Macrophages are heterogeneous and their phenotype and functions are regulated by the surrounding micro‐environment. Macrophages commonly exist in two distinct subsets: 1) Classically activated or M1 macrophages, which are pro‐inflammatory and polarized by lipopolysaccharide (LPS) either alone or in association with Th1 cytokines such as IFN‐γ, GM‐CSF, and produce pro‐inflammatory cytokines such as interleukin‐1β (IL‐1β), IL‐6, IL‐12, IL‐23, and TNF‐α; and 2) Alternatively activated or M2 macrophages, which are anti‐inflammatory and immunoregulatory and polarized by Th2 cytokines such as IL‐4 and IL‐13 and produce anti‐inflammatory cytokines such as IL‐10 and TGF‐β. M1 and M2 macrophages have different functions and transcriptional profiles. They have unique abilities by destroying pathogens or repair the inflammation‐associated injury. It is known that M1/M2 macrophage balance polarization governs the fate of an organ in inflammation or injury. When the infection or inflammation is severe enough to affect an organ, macrophages first exhibit the M1 phenotype to release TNF‐α, IL‐1β, IL‐12, and IL‐23 against the stimulus. But, if M1 phase continues, it can cause tissue damage. Therefore, M2 macrophages secrete high amounts of IL‐10 and TGF‐β to suppress the inflammation, contribute to tissue repair, remodeling, vasculogenesis, and retain homeostasis. In this review, we first discuss the basic biology of macrophages including origin, differentiation and activation, tissue distribution, plasticity and polarization, migration, antigen presentation capacity, cytokine and chemokine production, metabolism, and involvement of microRNAs in macrophage polarization and function. Secondly, we discuss the protective and pathogenic role of the macrophage subsets in normal and pathological pregnancy, anti‐microbial defense, anti‐tumor immunity, metabolic disease and obesity, asthma and allergy, atherosclerosis, fibrosis, wound healing, and autoimmunity.
Clinical translation of MS-based, quantitative plasma proteomics: status, challenges, requirements, and potential

ABSTRACT Introduction: Aided by the advent of advanced mass spectrometry (MS)-based technologies and methodologies, quantitative proteomics has emerged as a viable technique to capture meaningful data for candidate biomarker evaluation. To aid clinical translation, these methods generally utilize a bottom-up strategy with isotopically labeled standards and a targeted form of MS measurement. Areas covered: This article reviews the status, challenges, requirements, and potential of translating current, MS-based methods to the clinical laboratory. The described methods are discussed and contrasted within a fit-for-purpose approach, while different resources for quality control, quantitative analysis, and data interpretation are additionally provided. Expert commentary: Although great strides have been made over the past five years in developing reliable quantitative assays for plasma protein biomarkers, it is crucial for investigators to have an understanding of the clinical validation process, a major roadblock in translational research. Continued progress in method design and validation of protein assays is necessary to ultimately achieve widespread adoption and regulatory approval.
Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies

Glycosylphosphatidylinositol (GPI)-anchored proteins are ubiquitously expressed in the human body and are important for various functions at the cell surface. Mutations in many GPI biosynthesis genes have been described to date in patients with multi-system disease and together these constitute a subtype of congenital disorders of glycosylation. We used whole exome sequencing in two families to investigate the genetic basis of disease and used RNA and cellular studies to investigate the functional consequences of sequence variants in the PIGY gene. Two families with different phenotypes had homozygous recessive sequence variants in the GPI biosynthesis gene PIGY. Two sisters with c.137T>C (p.Leu46Pro) PIGY variants had multi-system disease including dysmorphism, seizures, severe developmental delay, cataracts and early death. There were significantly reduced levels of GPI-anchored proteins (CD55 and CD59) on the surface of patient-derived skin fibroblasts (∼20–50% compared with controls). In a second, consanguineous family, two siblings had moderate development delay and microcephaly. A homozygous PIGY promoter variant (c.-540G>A) was detected within a 7.7 Mb region of autozygosity. This variant was predicted to disrupt a SP1 consensus binding site and was shown to be associated with reduced gene expression. Mutations in PIGY can occur in coding and non-coding regions of the gene and cause variable phenotypes. This article contributes to understanding of the range of disease phenotypes and disease genes associated with deficiencies of the GPI-anchor biosynthesis pathway and also serves to highlight the potential importance of analysing variants detected in 5′-UTR regions despite their typically low coverage in exome data.