Search Results (30)

Galactic cosmic rays (GCRs), composed of protons and atomic nuclei, are accelerated in sources such as supernova remnants and pulsar wind nebulae, reaching energies up to the PeV range. As they propagate through the interstellar medium, their interactions with dense regions like molecular clouds produce secondary particles, including gamma-rays and neutrinos. In this study, we use the Geant4 Monte Carlo toolkit to simulate secondary particle production from GCR interactions within the Perseus molecular cloud, a nearby star-forming region. Our model incorporates realistic cloud composition, a wide range of incidence angles, and both hadronic and electromagnetic processes across a broad energy spectrum. The results highlight molecular clouds as significant sites of multi-messenger emissions and contribute to understanding the propagation of GCRs and the origin of diffuse gamma-ray and neutrino backgrounds in the Galaxy. Full article

Objectives: This study aimed to evaluate the effects of different titanium (Ti) anodized surfaces on soft tissue healing around dental implant abutments. Methods: Discs of machined (MC), pink anodized (PA) and yellow anodized (YA) surfaces were morphologically characterized and evaluated in vitro. Cell adhesion and collagen synthesis by human gingival fibroblasts (hGFs) were assessed to evaluate the regenerative potential of the surfaces under study. Their inflammatory potential was evaluated in THP-1 cell cultures by measuring cytokine secretion, and their proteomic adsorption patterns were characterized using nano-liquid chromatography mass spectrometry (nLC-MS/MS). Statistical significance was considered at 5%. In relation to proteomics, statistical differences were evaluated using the Student t-test with the Perseus application. Results: The anodization process resulted in a reduction in the surface roughness parameter (Ra) relative to the machined titanium (p < 0.05). No differences in hGF adhesion were found between the surfaces after one day. PA induced increased hGF collagen synthesis after 7 days (p < 0.05). The secretion of TNF-α was lower for anodized surfaces than for MC, and its concentration was lower for PA than for YA (p < 0.05). In turn, TGF-β was higher for PA and YA versus MC after one and three days of culture. A total of 176 distinct proteins were identified and 26 showed differences in adhesion between the anodized surfaces and MC. These differential proteins were related to coagulation, lipid metabolism, transport activity, plasminogen activation and a reduction in the immune response. Conclusions: Anodized Ti surfaces showed promising anti-inflammatory and regenerative potential for use in dental implant abutments. Anodization reduced surface roughness, increased collagen synthesis and lowered TNF-α secretion while increasing TGF-β levels compared to machined surfaces. Identified proteins related to coagulation and lipid metabolism supported these findings. Clinical relevance: Anodized surfaces could offer improved short-term peri-implant soft tissue healing over machined surfaces. The analysis of abutment surface, instead of implant surface, is a new approach that can provide valuable information. Full article

Peritoneal fluid (PF) is intimately associated with the gastrointestinal tract, and changes in the PF may directly reflect abdominal pathology. We aimed to quantify differences in the PF proteome between intestinal lesion type (ischemic vs. non-ischemic) and location (small vs. large intestine). PF samples were collected at hospital admission from horses presenting for abdominal pain (colic). Cases were clinically categorized by lesion type and location after resolution (10 per group). PF proteins were extracted and quantified by label-free liquid chromatography-tandem mass spectroscopy. Data were analyzed in Perseus and R, with functional annotation by UniProtKB and interaction visualization in STRING. Sixteen proteins unique to ischemic lesions and twelve unique to small intestinal lesions had significant network enrichment with functions related to inflammatory and immune responses. Identified proteins related to ischemic and small intestinal lesions included calprotectin, lactotransferrin, alpha 2 macroglobulin, and serine proteases/protease inhibitors, as well as apolipoprotein B and lipid metabolism pathways not previously described in relation to ischemic intestinal disease. While no single biomarker is expected to adequately diagnose or predict the outcome of equine colic, the proteins identified here should be considered as candidates for further study in a larger population. Full article

Background/Objectives: In adolescent patients with ulcerative colitis refractory to anti-tumor necrosis factor (TNF) therapy, episodes of acute severe ulcerative colitis (ASUC) require hospitalization or surgery. Upadacitinib can be a potential colectomy-sparing agent in adult ASUC patients receiving intensified dosing. Methods: This case series evaluates clinical outcomes of intensified rescue upadacitinib dosing in adolescent patients with ASUC. We included adolescents admitted with anti-TNF refractory ASUC treated with 30 mg twice daily upadacitinib. The primary outcome was the proportion of patients who remained colectomy-free at the most recent follow-up. Results: Five patients (aged 14–18) exhibited varying responses to upadacitinib; 2 responded rapidly, while 3 had partial response. All the patients remained on upadacitinib and were colectomy-free during follow-up (55–203 days). Three (60%) ultimately received dual advanced therapy with ustekinumab and upadacitinib. At most recent follow-up, 60% were in clinical/biochemical remission without corticosteroids. Conclusions: In select cases, intensified upadacitinib may be a potential colectomy-sparing option for adolescent ASUC patients refractory to anti-TNF therapy. Full article

Background: Chinese hamster ovary (CHO) cells are extensively used in the pharmaceutical industry for producing complex proteins, primarily because of their ability to perform human-like post-translational modifications. However, the efficiency of high-quality protein production can vary significantly for monoclonal antibody-producing cell lines, within the CHO host cell lines or by extrinsic factors. Methods: To investigate the complex cellular mechanisms underlying this variability, a phosphoproteomics analysis was performed using label-free quantitative liquid chromatography after a phosphopeptide enrichment of recombinant CHO cells producing two different antibodies and a tunicamycin treatment experiment. Using MaxQuant and Perseus for data analysis, we identified 2109 proteins and quantified 4059 phosphosites. Results: Significant phosphorylation dynamics were observed in nuclear proteins of cells producing the difficult-to-produce 2G12 mAb. It suggests that the expression of 2G12 regulates nuclear pathways based on increases and decreases in phosphorylation abundance. Furthermore, a substantial number of changes in the phosphorylation pattern related to tunicamycin treatment have been detected. TM treatment affects, among other phosphoproteins, the eukaryotic elongation factor 2 kinase (Eef2k). Conclusions: The alterations in the phosphorylation landscape of key proteins involved in cellular processes highlight the mechanisms behind stress-induced cellular responses. Full article

Background: The purpose of this study was to detect proteomic alterations and corresponding signaling pathways involved in the formation of age-related cataract (ARC), diabetic cataract (DC), and post-vitrectomy cataract (PVC). Methods: Three sample types, the aqueous humor (AH), the anterior capsule (AC), and the content of the phaco cassette, were collected during phacoemulsification surgery. The samples were obtained from 12 participants without diabetes mellitus (DM), 11 participants with DM, and 7 participants without DM, with a history of vitrectomy surgery in the past 12 months. The Sp3 protocol (Single-Pot, Solid-Phase, Sample-Preparation) was used for the sample preparation. The recognition and quantification of proteins were carried out with liquid chromatography online with tandem mass spectrometry. The DIA-NN software was applied for the identification and quantification of peptides/proteins. Statistical analysis and data visualization were conducted on Perseus software. Data are available via ProteomeXchange. Results: A very rich atlas of the lens and AH proteome has been generated. Glycosaminoglycan biosynthesis and the non-canonical Wnt receptor signaling pathway were differentially expressed in ARC compared to both the DC and PVC groups. In the PVC group, complement activation was differentially expressed in AH samples, while glutathione metabolism and oxidoreductase activity were differentially expressed in AC samples. Microfilament motor activity, microtubule cytoskeleton organization, and microtubule binding were differentially expressed in the DC and PVC groups in both AH and AC samples. Conclusions: The results of this study expand the existing knowledge on pathways involved in the pathophysiology of cataract, and suggest possible important druggable targets for slower progression or even prevention of cataract. Full article

We employed data from the Spitzer Space Telescope to investigate the presence of the aromatic amino acids tyrosine and phenylalanine in the interstellar gas of the young star cluster IC 348. Our analysis revealed emission lines in the observed spectrum that closely matched the strongest mid-infrared laboratory bands associated with tyrosine and phenylalanine in terms of wavelength and intensity. Through flux measurements, we estimated column densities along the line of sight toward the core of IC 348, ranging from 0.8–1.0 × 10¹¹ cm⁻². Additionally, these emission lines were evident in the combined spectra of more than 30 interstellar locations spanning various unrelated star-forming regions observed by Spitzer, indicating a widespread distribution of the molecules responsible for the emission throughout interstellar space. Prospective endeavors employing high spectral resolution mid-infrared searches for proteinogenic amino acids in protostars, protoplanetary disks, and the interstellar medium will play a pivotal role in elucidating the external origins of meteoritic amino acids and understanding the prebiotic conditions that laid the groundwork for life on early Earth. Full article

This study investigated whether manual integration in the recognition of the endothelial cells produces different outcomes of morphometric parameters compared to a fully automatic approach. Eight hundred and ninety endothelial images, originally acquired by the Perseus Specular Microscope (CSO, Florence, Italy), from seven positions of right and left corneas were selected from the database of the Research Centre in Optics and Optometry at the University of Milano-Bicocca. For each image selected, two procedures of cell identification were performed by the Perseus: an automatic identification and a manual-integrated procedure to add potential additional cells with the available editing tool. At the end of both procedures, the endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX) of the mosaic were calculated. The HEX in the two procedures was significantly different for all comparisons (p < 0.001), but clinically negligible. No significant differences were found for the CV and ECD in the images of both eyes irrespective of the corneal position of acquisition (except for ECD in three corneal portions, p < 0.05). To conclude, it is possible to recognise a significantly higher number of cells using the manual-integrated procedure than it is using the fully automatic one, but this does not change the morphological parameters achieved. Full article

We present a model-independent method for separating the spectral counterparts of the active galactic nucleus (AGN) NGC 1275 from the surrounding emission of the Perseus cluster, as observed by Suzaku/XIS cameras. The Perseus cluster emission extends to higher energies than typically observed in AGN environments, reaching up to 9–10 keV. This necessitates precise separation of AGN and cluster spectra. To circumvent the degeneracy arising from numerous spectral fitting parameters, including elemental abundances, thermal and Compton emissions from the nucleus, and spectral parameters of the jet synchrotron self-Compton/inverse Compton emissions, we avoid traditional spectral fitting methods. Instead, we leverage spatial resolution and employ a double background subtraction approach. We apply this procedure to the complete set of Suzaku/XIS observational data for NGC 1275, resulting in cleaned spectra and a light curve of the AGN emission in this system. To demonstrate the applicability of our method, we also utilize the available XMM-Newton/EPIC data. Full article

According to the World Health Organization (WHO), major depressive disorder (MDD) is the fourth leading cause of disability worldwide and the second most common disease after cardiovascular events. Approximately 280 million people live with MDD, with incidence varying by age and gender (female to male ratio of approximately 2:1). Although a variety of antidepressants are available for the different forms of MDD, there is still a high degree of individual variability in response and tolerability. Given the complexity and clinical heterogeneity of these disorders, a shift from “canonical treatment” to personalized medicine with improved patient stratification is needed. OPADE is a non-profit study that researches biomarkers in MDD to tailor personalized drug treatments, integrating genetics, epigenetics, microbiome, immune response, and clinical data for analysis. A total of 350 patients between 14 and 50 years will be recruited in 6 Countries (Italy, Colombia, Spain, The Netherlands, Turkey) for 24 months. Real-time electroencephalogram (EEG) and patient cognitive assessment will be correlated with biological sample analysis. A patient empowerment tool will be deployed to ensure patient commitment and to translate patient stories into data. The resulting data will be used to train the artificial intelligence/machine learning (AI/ML) predictive tool. Full article

Baldassarre Peruzzi’s cosmological vault fresco (1510–11) in the Villa Farnesina in Rome, prominently featuring a scene of Perseus and Medusa, showcases a dynamic operation that was often at work in the early modern period between the beholder and an immobile work of art. These types of representational objects participate in the discourse around materiality, not by employing the signifying powers of their constituent materials, but by encouraging thought about their material presence. I explore the process of haptic engagement that the fresco painting urges in its beholders, raising the possibility that the trope of petrification, made popular by Dante and other Italian writers of amorous poems, unlocks the work’s layered meaning. Full article

The human quest for sustainable habitation of extraterrestrial environments necessitates a robust understanding of life’s adaptability to the unique conditions of spaceflight. This study provides a comprehensive proteomic dissection of the Arabidopsis plant’s responses to the spaceflight environment through a meta-analysis of proteomics data from four separate spaceflight experiments conducted on the International Space Station (ISS) in different hardware configurations. Raw proteomics LC/MS spectra were analyzed for differential expression in MaxQuant and Perseus software. The analysis of dissimilarities among the datasets reveals the multidimensional nature of plant proteomic responses to spaceflight, impacted by variables such as spaceflight hardware, seedling age, lighting conditions, and proteomic quantification techniques. By contrasting datasets that varied in light exposure, we elucidated proteins involved in photomorphogenesis and skotomorphogenesis in plant spaceflight responses. Additionally, with data from an onboard 1 g control experiment, we isolated proteins that specifically respond to the microgravity environment and those that respond to other spaceflight conditions. This study identified proteins and associated metabolic pathways that are consistently impacted across the datasets. Notably, these shared proteins were associated with critical metabolic functions, including carbon metabolism, glycolysis, gluconeogenesis, and amino acid biosynthesis, underscoring their potential significance in Arabidopsis’ spaceflight adaptation mechanisms and informing strategies for successful space farming. Full article

Knee alignment after total knee arthroplasty (TKA) is essential for implant survival. Several studies on accelerometer-based navigation systems have given controversial results, with or without improvement in knee alignment. The aim was to evaluate the accuracy of an accelerometer-based navigation system for tibial resection during total knee arthroplasty. Twenty TKAs performed with an accelerometer-based navigation system were included in this prospective–comparative study. They were matched (on age, body mass index, and preoperative mechanical axis of the lower limb) in a 2:1 ratio with TKA performed with a conventional technique. The objective of this study was to determine the accuracy of the Perseus System for making the tibial cut on TKA. The primary endpoint was the tibial mechanical angle (TMA) measured on radiographic images at two months postoperatively. Secondary endpoints were the tibial slope and the mechanical axis of the lower limb (HKA angle, Hip-Knee-Ankle). The mean TMA in the accelerometer group was 87.6 ± 2.1° versus 89.1 ± 1.6° in the control group (p < 0.01). The tibial slope in the accelerometer group was 90.0 ± 1.9° versus 89.9 ± 1.3° in the control group (not significant). The mean HKA was 177.7 ± 1.8° in the accelerometer group and 177.5 ± 2.2° in the control group (not significant). This accelerometer-based navigation system during TKA did not improve the accuracy of the tibial cut compared to the conventional technique, but it restored the tibial slope. Full article

Osteosarcoma is a malignant tumor that produces neoplastic bone or osteoid osteoma. In human multicentric osteosarcoma (HMOS), a unique variant of human osteosarcoma (HOS), multiple bone lesions occur simultaneously or asynchronously before lung metastasis. HMOS is associated with an extremely poor prognosis, and effective treatment options are lacking. Using the proteins in our previously generated HMOS cell lines as antigens, we generated antibodies using a human antibody phage library. We obtained antibody clones recognizing 95 independent antigens and developed a fluorescence probe-based enzyme-linked immunosorbent assay (ELISA) technique capable of evaluating the reactivity of these antibodies by fluorescence intensity, allowing simple, rapid, and high-throughput selection of antibody clones. These results were highly correlated with those using flow cytometry. Subsequently, the HMOS cell lysate was incubated with the antibody, the antigen–antibody complex was recovered with magnetic beads, and the protein bands from electrophoresis were analyzed using liquid chromatography-mass spectrometry (LC/MS). CAVIN1/polymerase I transcript release factor was specifically detected in the HMOS cells. In conclusion, we found via a novel high-throughput screening method that CAVIN1/PTRF is an HMOS-specific cell membrane biomarker and an antigen capable of producing human antibodies. In the future, antibody–drug conjugate targeting of these specific proteins may be promising for clinical applications. Full article

The article presents the building of an event-centric model for the computational representation of crisis events using an ontology encoded in the Web Ontology Language (OWL). The work presented here is done in collaboration with the Leaders and Crisis Management in Ancient Literature. A Comparative Approach (LACRIMALit) project, (2022–2025) hosted at the Institute for Mediterranean Studies/Foundation for Research and Technology (IMS-FORTH). A key outcome of the project is the LACRIMALit ontology that aims principally at the semantic annotation of ancient Greek historiographical texts in open access via Perseus Digital Library. The ontology will facilitate reasoning on and across these documents and enable their semantic querying. The tagset of annotations, concepts, relations, and terms of the ontology will be both human and machine readable, extensible and reusable. The annotated corpus of texts to be produced will be available for sophisticated queries based on the concepts and relations, defined by the ontologies. This will considerably improve the string-based querying of the texts in their present digital format. This article presents the principles of conceptualization of the domain in the three dimensions: domain knowledge (mainly classes illustrated with some individuals), linguistic dimension (terms, proper names, definite descriptions), and references. Full article