Miracle-dz/UniFAR-FTUs huggingface dataset:
Processing of bacterial antigens for peptide presentation on MHC class I molecules

Summary: Professional antigen‐presenting cells (pAPC) can process and present exogenous antigens on major histocompatibility complex class 1 (MHC‐I) molecules. This unusual pathway for antigen presentation may represent a physiologically important step in the course of priming and tolerance induction of CD8+ T cells. In addition, it may play an important role in immunological surveillance for pathogens that survive in vacuolar compartments in APC. The goal of the present review is to discuss recent studies on the processing of bacterial‐derived antigens for presentation on MHC‐1 molecules. The antigen presentation emphasized will include bacteria that remain confined in vacuolar compartments. This is in contrast to antigens derived from bacteria that have intrinsic properties allowing translocation across membranes and access into the classical MHC‐I presentation pathway In particular, presentation of bacterial antigens by dendritic cells (DC) will be emphasized, and MHC‐I presentation of antigens derived from apoptotic cells, particularly cells induced to undergo apoptosis by microbial infection, will be presented. Finally, some special aspects of the interaction between bacteria and DC will be discussed as ii relates to DC maturation, antigen presentation and T‐cell stimulation.
Effect of Increased Ascorbic Acid Blood Levels on the Ascorbic Acid Level in Treated and Non-treated Gingiva

There is general agreement regarding the effects of ascorbic acid deficiency on the gingiva and periodontal tissues of experimental animals. Opinions have differed, however, regarding the significance of ascorbic acid deficiency in the etiology of gingival and periodontal disease in humans. '-12 We were interested in determining whether the ascorbic acid level of the gingiva would be affected when the blood level was elevated by the systemic administration of ascorbic acid. An experiment was undertaken in humans for this purpose.
Overexpression of Copper and Zinc Superoxide Dismutase in Transgenic Mice Prevents the Induction and Activation of Matrix Metalloproteinases after Cold Injury-Induced Brain Trauma

Matrix metalloproteinases (MMPs), a family of proteolytic enzymes which degrade the extracellular matrix, are implicated in blood—brain barrier disruption, which is a critical event leading to vasogenic edema. To investigate the role of reactive oxygen species (ROS) in the expression of MMPs in vasogenic edema, the authors measured gelatinase activities before and after cold injury (CI) using transgenic mice that overexpress superoxide dismutase-1. A marked induction of pro-gelatinase B (pro-MMP-9) was seen 2 hours after CI and was maximized at 12 hours in wild-type mice. The pro-MMP-9 level was significantly lower in transgenic mice 4 hours (P < 0.001) and 12 hours (P < 0.05) after CI compared to wild-type mice. The activated MMP-9 was detected from 6 to 24 hours after injury. A mild induction of pro-gelatinase A (pro-MMP-2) was seen at 6 hours and was sustained until 7 days. In contrast, the activated form of MMP-2 appeared at 24 hours, was maximized at 7 days, and was absent in transgenic mice. Western blot analysis showed that the tissue inhibitors of metalloproteinases were not modified after CI. The results suggest that ROS production after CI may contribute to the induction and/or activation of MMPs and could thereby exacerbate endothelial cell injury and the development of vasogenic edema after injury.
A scanning electron microscopy study of human osteoblast morphology on five orthopedic metals.

Despite the long-standing use of metals as orthopedic implants there still are unsolved problems with these materials and open questions about their behavior in a biological environment. Cell-culture studies provide a useful tool for investigations. In addition to the determination of biochemical or molecular biological parameters, the morphology of adhering cells reflects their interaction with the substrata. This article describes an investigation of the morphology of human osteoblasts on stainless steel, cobalt chromium alloy, commercially pure titanium, Ti-6Al-4V, and Ti-6Al-7Nb with surface designs similar to those used as clinical implants. A cell culture plastic surface was used as a control material. The materials were examined by scanning electron microscopy at different points of time. The cells spread, proliferated, and formed nodules on all test substrates in a time-dependent manner, without signs of a disturbing influence from any of the materials. On the smooth surfaces the cells showed a flattened fibroblast-like morphology and only slight differences could be detected. Therefore, the cellular morphology seems not to be markedly affected by the different chemical material compositions. In contrast, the titanium alloy with a rough, sandblasted surface induced a three-dimensional growth. This three-dimensional cellular network could be the basis for the known earlier differentiation of osteoblasts on rough surfaces in vitro and a better osseointegration in vivo.
Towards collective protections for crowdworkers

The ‘sharing economy’ and the collaborative economy are shaping new forms of employment in which digital platforms enable multilateral work relationships. This article discusses some initiatives aimed at the collective protection of crowdworkers. The first section investigates whether it is possible to extend EU labour protection – in particular, collective rights – to independent digital contractors. The second section looks at whether the national level may offer more effective measures for economically dependent digital workers or for distance workers, by comparing three selected countries: Italy, France and Spain. The article then explores the possibility of extending to crowdworkers the protections offered by collective bargaining and addresses how trade unions could have a role in implementing guarantees for crowdworkers. Comparative analysis is used to show how different constitutional systems recognise freedom of association, especially in relation to ‘subordinated’ workers. A strategy of viewing collective rights as human rights could be applied in order to reduce the contractual weakness of self-employed workers on digital platforms – and might even form the basis of a bill of rights.
[Expression of cell cycle regulators in squamous cell carcinoma of maxillary sinus and their significance].

OBJECTIVE To investigate the clinicopathlogical significance of cyclinE, cyclinD1, P21WAF1/CIP1 and P27KIP1 expression in squamous cell carcinoma of maxillary sinus. METHODS The expression of cyclinE, cyclinD1, P21WAF1/CIP1 and P27KIP1 was examined by the method of immunohistochemistry in inflammatory mucosa of maxillary sinus(10), inverting papilloma of maxillary sinus(20) and squamous cell carcinoma of maxillary sinus (50). RESULTS (1) In inflammatory mucosa, inverting papilloma and squamous cell carcinoma, the positive immunostaining rates of cyclinD1 protein were 10.0%, 25.0%, 48.0% respectively (P < 0.05); cyclinE protein was 20.0%, 35.0%, 58.0% respectively (P < 0.05); P21WAF1/CIP1 protein was 80.0%, 65.0%, 40.0% respectively (P < 0.05) and P27KIP1 protein was 70.0%, 75.0%, 40.0% respectively (P < 0.05). (2) There was no significance between the clinical type, T stage and clinical stage of carcinoma of maxillary sinus and the expression of cyclinD1, cyclinE, P21WAF1/CIP1 and P27KIP1 (P > 0.05). (3) P21WAF1/CIP1 positive expression in highly, moderately and poorly differtiated carcinomas were 73.2% (11/15), 58.9% (11/19), 25.0% (4/16) respectively (P < 0.05). CONCLUSION (1) With the development of the lesion, the positive immunostaining rate of cyclinE and cyclinD1 protein increases, while the rate of P21WAF1/CIP1 and P27KIP1 protein decreases. (2) P21WAF1/CIP1 expression is associated with tumour cell differentiation. (3) The mutual mechenism of cell cycle regulators plays an important role in the squamous cell carcinoma of maxillary sinus. The quantity and the frequency of four kinds of gene expression increase with the progression of maxillary sinus carcinogenesis.
Phase 1 Study of Tirapazamine in Combination With Radiation and Weekly Cisplatin in Patients With Locally Advanced Cervical Cancer

Introduction: Hypoxia is an adverse prognostic factor in locoregionally advanced cervical cancer treated with radiation. The aim of this phase I study was to develop a well-tolerated regimen that added tirapazamine to the standard regimen of radiation and weekly low-dose cisplatin. Methods: Eligible patients had previously untreated carcinoma of the cervix, stages IB2 to IVA. The starting schedule was radiotherapy (45-50.4 Gy external beam radiation followed by brachytherapy), with concomitant weekly intravenous cisplatin, 40 mg/m2 on weeks 1 to 6 and weekly intravenous tirapazamine, 290 mg/m2 in weeks 1 to 5. Results: Eleven patients were enrolled. The median age was 52 years (range, 31-65 years). Ten patients had squamous cell carcinoma and 1 patient had adenocarcinoma; 5 patients had stage 1B2 disease, 1 had stage IIA, 3 had stage IIB-3, 1 had stage IIIB, and 1 had stage IVA. The first 2 patients on dose level 1 experienced a dose-limiting toxicity (DLT): 1 experienced grade 3 alanine amino transferase elevation and grade 4 pulmonary embolism, and 1 experienced grade 3 ototoxicity. Doses were decreased to dose level −1 with a 30-mg/m2 dose of cisplatin and a 260-mg/m2 dose of tirapazamine. Three patients were treated without any DLTs. Six patients were then treated on dose level −1a: a 35-mg/m2 dose of cisplatin and a 260-mg/m2 doses of tirapazamine with 2 DLTs-grade 3 neutropenia with dose omission and grade 4 pulmonary embolism with major hemodynamic compromise. Three of 10 evaluable patients have experienced locoregional failure. Conclusions: The combination of weekly tirapazamine and cisplatin with radiation for locally advanced cervical cancer was associated with more toxicity than anticipated with the recommended dose level being tirapazamine 260 mg/m2 and cisplatin 30 mg/m2. Further study of this weekly schedule is not warranted.
Etanercept in the treatment of palmoplantar pustulosis.

INTRODUCTION Palmoplantar pustulosis (PPP) is a chronic, recurrent and difficult to treat skin condition characterized by the presence of pustules, erythema, and hyperkeratosis on palms and soles. METHODS Fifteen subjects with PPP were randomized (2:1) to receive subcutaneous injections of either etanercept 50 mg or a placebo twice a week for 3 months. All subjects then received the etanercept 50 mg injections twice a week for an additional 3 months. RESULTS Etanercept was well tolerated by subjects with PPP. The decrease in median Palmoplantar Pustulosis Area and Severity Index (PPPASI) score from baseline to 24 weeks was statistically significant for subjects treated with etanercept for 24 weeks (P = 0.038, n = 10) but not for subjects in the placebo/etanercept cross-over group (P = 0.125, n = 5). Comparison of changes in PPPASI from baseline to week 12 was not statistically significant for subjects assigned to etanercept or to placebo. Some subjects treated with etanercept presented good clinical improvements in PPP severity whereas others showed an increase in PPP severity. CONCLUSION This study showed that etanercept was well tolerated in subjects with PPP and suggests that some PPP subjects might benefit from etanercept therapy. Larger studies are needed to assess PPP response to etanercept including the influence of smoking and the presence or absence of psoriasis outside palms and soles.
Isoproterenol regulates tumour necrosis factor, interleukin‐10, interleukin‐6 and nitric oxide production and protects against the development of vascular hyporeactivity in endotoxaemia

Pro‐inflammatory cytokines, such as tumour necrosis factor (TNF) and free radicals, such as nitric oxide (NO), are mediators of endotoxaemia. Catecholamines are in clinical use to treat the haemodynamic consequences of severe septic shock. Beta‐adrenergic agonists exert many of their effects by elevation of intracellular cyclic AMP (cAMP) concentration. Cyclic AMP can modulate endotoxin‐induced cytokine and NO production. Here we investigate the effect of isoproterenol pretreatment on the cytokine and NO production induced by bacterial lipopolysaccharide (LPS, 4–10 mg/kg). Pretreatment with isoproterenol (10 mg/kg) blunted the LPS‐induced TNF response, increased the LPS‐induced formation of interleukin‐10 and interleukin‐6 and reduced the LPS‐induced production of NO in conscious mice. In anaesthetized rats, pretreatment with isoproterenol prevented the LPS‐induced suppression of vascular contractility to norepinephrine in the thoracic aorta ex vivo. The hyporeactivity is due to expression of the inducible isoform of NO synthase (iNOS) and was restored by in vitro administration of NG‐methyl‐l‐arginine (l‐NMA), an inhibitor of NO synthase. However, l‐NMA did not alter vascular contractility in control vessels or in rings taken from the LPS‐treated rats pretreated with isoproterenol. Our findings suggest that, in addition to its haemodynamic actions, isoproterenol may also exert beneficial effects by modulating the endotoxin‐induced inflammatory response.
Path planning applied to the mobile robot GBot

The main idea of this paper is to present a general description of the project “path planning applied to a mobile robot GBot”, which includes items such as the approach taken, the implemented techniques in areas like digital image processing and path planning in mobile robots. Furthermore, there is a section that presents the performance and a small analysis of the implemented system. The problem treated in this paper, is based on the need to develop a system that allows to a robot to go from a starting point to an end point. Without mishaps or collisions through the shortest possible route between two points. To achieve this, we use color segmentation as main technique of digital image processing. While in path planning, you will found within this work that the main tool is the Voronoi diagram combined with the search Dijkstra algorithm.
CD19 Is Linked to the Integrin-associated Tetraspans CD9, CD81, and CD82*

The CD19-CD21-CD81 complex regulates signal transduction events critical for B lymphocyte development and humoral immunity. CD81, a molecule with 4 transmembrane domains, member of the tetraspan superfamily, is engaged, together with other tetraspans such as CD9, CD53, CD63, and CD82, in multimolecular complexes containing β1 integrins and major histocompatibility complex antigens. Here we demonstrate that two other tetraspans, CD82 and the early B cell marker CD9, are coimmunoprecipitated with CD19 from Brij97 lysates of B cell lines. Moreover, CD9 was coprecipitated from lysates of purified CD10+ early B cells. These associations were confirmed by the cocapping of CD19 with CD9 or CD82. The CD9/CD19 association was disrupted in the presence of digitonin, contrary to the CD81/CD19 association, indicating that CD9 and CD81 interact with CD19 in different ways. The CD9/CD81 association is also disrupted in the presence of digitonin, suggesting that CD9 associates with CD19 only through CD81. To characterize the regions involved in the CD81/CD19 association, two reciprocal CD9/CD81 chimeric molecules were tested for the association with CD19, but none of them could be coprecipitated with CD19 in digitonin, indicating that the domain of CD81 responsible for its association with CD19 is complex. Finally, engagement of CD9 could induce the tyrosine phosphorylation of different proteins, including CD19 itself, suggesting that the CD9/CD19 association is functionally relevant. Thus, a physical and functional link is formed between the CD19-CD21-CD81 complex and the integrin-tetraspan complexes, which is dynamically modulated in the process of B cell differentiation.
Lipid and Apoprotein Profile in HIV-1-Infected Patients After CD4-Guided Treatment Interruption

Objectives:The aims of the present study were to determine if metabolic abnormalities and cytokine derangements are modified in HIV-1-infected patients after 12 months on treatment interruption (TI). Design:The design of this study was prospective randomized study. Methods:Longitudinal multicenter study in HIV-1-infected patients with a 12-month follow-up. Patients on stable highly active antiretroviral therapy, with CD4 count >600/μL and HIV RNA <50 copies/mL for at least 6 months, were randomized to interrupt therapy or continue ongoing highly active antiretroviral therapy. Lipids (total cholesterol, triglycerides), apoproteins (A1, B, and E), and adipocytokines (leptin, adiponectin, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, Interleukin-6, Interleukin-8, and tumor necrosis factor-α) were measured at baseline and at month 12. Multiplex suspension bead array immunoassay was performed using the Luminex 100 analyzer to identify protein expression in plasma. Results:Patients who underwent TI (n = 19) had a significant decrease in median cholesterol levels (P < 0.001), while median triglyceride levels remained unchanged. There was a significant decrease in Apo-A1 levels (P = 0.048) and Apo-B levels (P < 0.001) and an increase in tumor necrosis factor-α levels (P = 0.034). Given the greater decrease in Apo-B, the ratio Apo-A1/Apo-B increased after 12 months of TI (from 3.4 to 5.1, P = 0.008). We did not find significant variations in leptin or adiponectin levels. In patients who continued on highly active antiretroviral therapy (n = 18), there were no significant changes in any of the measured parameters. Conclusion:The lipid profile and apoproteins levels change toward a less atherogenic profile after TI, arguing against a lipid-mediated mechanism to explain the increased cardiovascular risk in patients who interrupt treatment.
Development of Resistance in Wild-Type and Hypermutable Pseudomonas aeruginosa Strains Exposed to Clinical Pharmacokinetic Profiles of Meropenem and Ceftazidime Simulated In Vitro

ABSTRACT In this study we investigated the interplay of antibiotic pharmacokinetic profiles and the development of mutation-mediated resistance in wild-type and hypermutable Pseudomonas aeruginosa strains. We used in vitro models simulating profiles of the commonly used therapeutic drugs meropenem and ceftazidime, two agents with high levels of antipseudomonal activity said to have different potentials for stimulating resistance development. During ceftazidime treatment of the wild-type strain (PAO1), fully resistant mutants overproducing AmpC were selected rapidly and they completely replaced wild-type cells in the population. During treatment with meropenem, mutants of PAO1 were not selected as rapidly and showed only intermediate resistance due to the loss of OprD. These mutants also replaced the parent strain in the population. During the treatment of the mutator P. aeruginosa strain with meropenem, the slowly selected mutants did not accumulate several resistance mechanisms but only lost OprD and did not completely replace the parent strain in the population. Our results indicate that the commonly used dosing regimens for meropenem and ceftazidime cannot avoid the selection of mutants of wild-type and hypermutable P. aeruginosa strains. For the treatment outcome, including the prevention of resistance development, it would be beneficial for the antibiotic concentration to remain above the mutant prevention concentration for a longer period of time than it does in present regimens.
Mechanisms for calcium sensing receptor-regulated stomatal closure in response to the extracellular calcium signal

In Arabidopsis, extracellular calcium (Ca2+o) promotes intracellular calcium (Ca2+i) transients and stomatal closure, which has been found to be regulated by the calcium sensing receptor (CAS). However, the detailed pathways for transducting the Ca2+o signal by CAS are still unclear. We found that nitric oxide (NO) and the hydrogen peroxide (H2O2) accumulated in the guard cell chloroplast were the two elements that act downstream of the CAS signaling and trigger the stomatal closure by prolonging Ca2+i transients.1 Here we provide more commentary on CAS-regulated H2O2 generation from chloroplast and Ca2+i transients in response to Ca2+o, as well as other potential mechanisms that may be involved in the CAS signaling pathway.
Cyclic appearance of cytoplasmic NOR–silver‐stained particles in sea urchin embryos

When sea urchin embryos were subjected to nucleolar organizer region (NOR)‐silver staining, densely stained particles were observed in the cytoplasm. The appearance of these cytoplasmic particles (CPs) was cell‐cycle dependent. During early development, the CPs were detected at interphase, but not during mitosis; they disappeared at metaphase and reappeared at telophase. The CPs appeared periodically even when embryos were treated with cytochalasin B or aphidicolin, which inhibits the progression of cytokinesis and nuclear division, respectively. By contrast, CPs were not detected in the colchicine‐treated embryos in which both cytokinesis and nuclear divisions were prevented. The CPs were observed only in the embryos whose stage was early blastula (about 6th to 7th cleavage) or earlier; no CPs were detected even at interphase in the embryos at late blastula (about 8th to 9th cleavage) or later. Electron microscopic evaluation showed CPs to be granular structures, similar to heavy bodies. Also, sodium dodecyl sulfate (SDS)–polyacrylamide gel electrophoresis (PAGE) showed that 95‐kDa and 38‐kDa proteins were the NOR–silver‐staining proteins in sea urchin embroys. These proteins existed during the course of the cell cycles. These results suggest that (1) the cyclic appearance of the CPs or heavy bodies is closely related to the cell cycle as well as the programming of the embryogenesis, but independent of the cycle of cytokinesis and nuclear division; (2) 95‐kDa and 38‐kDa proteins are the major NOR–silver‐staining proteins in sea urchin embryos.
Inoculum Effect with Cefazolin among Clinical Isolates of Methicillin-Susceptible Staphylococcus aureus: Frequency and Possible Cause of Cefazolin Treatment Failure

ABSTRACT Methicillin (meticillin)-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A β-lactamase (Bla) have been associated with cefazolin failures, but the frequency and impact of these strains have not been well studied. Here we examined 98 MSSA clinical isolates and found that 26% produced type A Bla, 15% type B, 46% type C, and none type D and that 13% lacked blaZ. The cefazolin MIC90 was 2 μg/ml for a standard inoculum and 32 μg/ml for a high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MICs of ≥16 μg/ml with 107 CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher cefazolin MICs than type B or C producers, while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the six patients who experienced cefazolin failure showed a cefazolin inoculum effect, while none from the six patients successfully treated with cefazolin showed an inoculum effect, suggesting an association between these strains and cefazolin failure (P = 0.09 by Fisher's exact test). In summary, 19% of MSSA clinical isolates showed a pronounced inoculum effect with cefazolin, a phenomenon that could explain the cases of cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses.