Modulation of the CD8+-T-cell response by CD4+ CD25+ regulatory T cells in patients with Hepatitis B virus infection

CD4+ CD25+ regulatory T cells have been shown to maintain peripheral tolerance against self and foreign antigens. In this study we analyzed the effect of circulating CD4+ CD25+ T cells on CD8+-T-cell responses of patients with chronic and resolved hepatitis B virus (HBV) infection. We demonstrated that circulating CD4+ CD25+ T cells modulate the function and expansion of HBV-specific CD8+ cells ex vivo in all patients, regardless of whether they have chronic or resolved HBV infection. The possible role of CD4+ CD25+ T cells in the pathogenesis of chronic HBV infection is not supported by these data. However, these results might have implications for optimizing future immunotherapeutic approaches to HBV treatment

Shared communications volume 1 a summary and literature review

This paper provides a review of examples from the literature of shared communication resources and of agencies and/or organizations that share communication resources. The primary emphasis is on rural, intelligent transportation system communications involving transit. Citations will not be limited, however, to rural activities, or to ITS implementation, or even to transit. In addition, the term ''communication'' will be broadly applied to include all information resources. Literature references to issues that contribute to both successful and failed efforts at sharing communication resources are reviewed. The findings of this literature review indicate that: (1) The most frequently shared communication resources are information/data resources, (2) Telecommunications infrastructure and technologies are the next most frequently shared resources, (3) When resources are successfully shared, all parties benefit, (4) A few unsuccessful attempts of sharing resources have been recorded, along with lessons learned, (5) Impediments to sharing include security issues, concerns over system availability and reliability, service quality and performance, and institutional barriers, (6) Advantages of sharing include financial benefits to agencies from using shared resources and benefits to the public in terms of congestion mitigation, information transfer (e.g., traveler information systems), mobility (e.g., welfare-to-work paratransit), and safety (e.g., speed of incident response, incident avoidance),more » (7) Technology-based solutions exist to address technology-based concerns, and (8) Institutional issues can be addressed through leadership, enhanced knowledge and skills, open communication, responsiveness, and attractive pricing structures.« le Document type: Repor

Exploring the global scientific literature on urban metabolism

Urban ecosystems can be conceptualized like living organisms supported by material and energy flows that allow the generation of ecosystem structures and functions and the production of goods and services. Urban metabolism accounts for the flows of materials, energy, resources, food, and people in cities, providing a framework for the study of the interactions between natural and socio-economic systems. In this paper, the global scientific literature on urban metabolism was explored to identify knowledge gaps and emerging research areas over the last decades. A bibliometric network analysis was implemented to generate maps based on network data of scientific publications displaying relationships among scientific journals, researchers, countries, and keywords. The total number of publications on urban metabolism from 1990 to 2019 resulted in 498 documents. USA and China resulted the first countries publishing on urban metabolism while among the journals, the Journal of Industrial Ecology and Journal of Cleaner Production resulted the first in the ranking. The co-occurrence network map of keywords showed that, over the last decade, the main focus of research on urban metabolism has shifted from environmental issues to environmental accounting and socio-economic aspects. Considering the importance of urban systems for the achievement of local and global sustainability goals, it is likely that the scientific literature on urban metabolism will continue growing over the next years. Being cities characterized by complex relationships between natural and socio-economic systems, it is desirable that future studies will explore the multidimensional features of urban metabolism through multi-criteria assessment frameworks

Evaluation of telomerase activity in nasal polyps

Background: The objective of this study was to assess if nasal polyps express telomerase activity and whether a difference could be found between the polyp and the surrounding mucosa of the middle meatus and between different portions of the polyp itself. Methods: Nine patients affected by nasal polyposis were included in this study; four of these patients had recurring polyposis. Telomerase activity was measured by telomeric repeat amplification protocol assay. In six patients, the telomeric repeat amplification protocol assay was performed on the polyp and on the mucosa from the ipsilateral middle meatus. In a polyp, we were able to investigate telomerase activity of its different portions, corresponding to pedicle and fundus. Results: Telomerase activity observed in nasal polyps was higher than that observed in samples from the ipsilateral middle meatus mucosa. High or intermediate telomerase activity was found to be related to predominant recurring polyposis. Conclusions: Therefore, it could be postulated that telomerase activity could be related with the tendency of polyps to recur

Intra-molecular coupling as a mechanism for a liquid-liquid phase transition

We study a model for water with a tunable intra-molecular interaction $J_\sigma$, using mean field theory and off-lattice Monte Carlo simulations. For all $J_\sigma\geq 0$, the model displays a temperature of maximum density.For a finite intra-molecular interaction $J_\sigma > 0$,our calculations support the presence of a liquid-liquid phase transition with a possible liquid-liquid critical point for water, likely pre-empted by inevitable freezing. For J=0 the liquid-liquid critical point disappears at T=0.Comment: 8 pages, 4 figure

Regulatory T cells in the immunodiagnosis and outcome of kidney allograft rejection

Acute rejection (AR) is responsible for up to 12% of graft loss with the highest risk generally occurring during the first six months after transplantation. AR may be broadly classified into humoral as well as cellular rejection. Cellular rejection develops when donor alloantigens, presented by antigen-presenting cells (APCs) through class I or class II HLA molecules, activate the immune response against the allograft, resulting in activation of naive T cells that differentiate into subsets including cytotoxic CD8(+) and helper CD4(+) T cells type 1 (TH1) and TH2 cells or into cytoprotective immunoregulatory T cells (Tregs). The immune reaction directed against a renal allograft has been suggested to be characterized by two major components: a destructive one, mediated by CD4(+) helper and CD8(+) cytotoxic T cells, and a protective response, mediated by Tregs. The balance between these two opposite immune responses can significantly affect the graft survival. Many studies have been performed in order to define the role of Tregs either in the immunodiagnosis of transplant rejection or as predictor of the clinical outcome. However, information available from the literature shows a contradictory picture that deserves further investigation

Early triple negative breast cancer: Conventional treatment and emerging therapeutic landscapes

Triple negative breast cancers (TNBCs) are characterized by worse prognosis, higher propensity to earlier metastases, and shorter survival after recurrence compared with other breast cancer subtypes. Anthracycline-and taxane-based chemotherapy is still the mainstay of treatment in early stages, although several escalation approaches have been evaluated to improve survival outcomes. The addition of platinum salts to standard neoadjuvant chemotherapy (NACT) remains controversial due to the lack of clear survival advantage, and the use of adjuvant capecitabine represents a valid treatment option in TNBC patients with residual disease after NACT. Recently, several clinical trials showed promising results through the use of poly ADP-ribose polymerase (PARP) inhibitors and by incorporating immunotherapy with chemotherapy, enriching treatment options beyond conventional cytotoxic agents. In this review, we provided an overview on the current standard of care and a comprehensive update of the recent advances in the management of early stage TNBC and focused on the latest emerging biomarkers and their clinical application to select the best therapeutic strategy in this hard-to-treat population

A Self-Attention Deep Neural Network Regressor for real time blood glucose estimation in paediatric population using physiological signals

With the advent of modern digital technology, the physiological signals (such as electrocardiogram) are being acquired from portable wearable devices which are being used for non-invasive chronic disease management (such as Type 1 Diabetes). The diabetes management requires real-time assessment of blood glucose which is cumbersome for paediatric population due to clinical complexity and invasiveness. Therefore, real-time non-invasive blood glucose estimation is now pivotal for effective diabetes management. In this paper, we propose a Self-Attention Deep Neural Network Regressor for real-time non-invasive blood glucose estimation for paediatric population based on automatically extracted beat morphology. The first stage performs Morphological Extractor based on Self-Attention based Long Short-Term Memory driven by Convolutional Neural Network for highlighting local features based on temporal context. The second stage is based on Morphological Regressor driven by multilayer perceptron with dropout and batch normalization to avoid overfitting. We performed feature selection via logit model followed by Spearman's correlation among features to avoid feature redundancy. We trained as tested our model on publicly available MIT/BIH-Physionet databases and physiological signals acquired from a T1D paediatric population. We performed our evaluation via Clarke's Grid error to analyse estimation accuracy on range of blood values under different glycaemic conditions. The results show that our tool outperformed existing regression models with 89% accuracy under clinically acceptable range. The proposed model based on beat morphology significantly outperformed models based on HRV features

hTERT Transduction Extends the Lifespan of Primary Pediatric Low-Grade Glioma Cells While Preserving the Biological Response to NGF

The neurotrophin nerve growth factor (NGF) modulates the growth of human gliomas and is able to induce cell differentiation through the engagement of tropomyosin receptor kinase A (TrkA) receptor, although the role played in controlling glioma survival has proved controversial. Unfortunately, the slow growth rate of low-grade gliomas (LGG) has made it difficult to investigate NGF effects on these tumors in preclinical models. In fact, patient-derived low-grade human astrocytoma cells duplicate only a limited number of times in culture before undergoing senescence. Nevertheless, replicative senescence can be counteracted by overexpression of hTERT, the catalytic subunit of telomerase, which potentially increases the proliferative potential of human cells without inducing cancer-associated changes. We have extended, by hTERT transduction, the proliferative in vitro potential of a human LGG cell line derived from a pediatric pilocytic astrocytoma (PA) surgical sample. Remarkably, the hTERT-transduced LGG cells showed a behavior similar to that of the parental line in terms of biological responses to NGF treatment, including molecular events associated with induction of NGF-related differentiation. Therefore, transduction of LGG cells with hTERT can provide a valid approach to increase the in vitro life-span of patient-derived astrocytoma primary cultures, characterized by a finite proliferative potential

Multiscale three-dimensional scaffolds for soft tissue engineering via multimodal electrospinning

A novel (scalable) electrospinning process was developed to fabricate bio-inspired multiscale three-dimensional scaffolds endowed with a controlled multimodal distribution of fiber diameters and geared towards soft tissue engineering. The resulting materials finely mingle nano- and microscale fibers together, rather than simply juxtaposing them, as is commonly found in the literature. A detailed proof of concept study was conducted on a simpler bimodal poly(ε-caprolactone) (PCL) scaffold with modes of fiber distribution at 600 nm and 3.3 μm. Three conventional unimodal scaffolds with mean diameters of 300 nm and 2.6 and 5.2 μm, respectively, were used as controls to evaluate the new materials. Characterization of the microstructure (i.e. porosity, fiber distribution and pore structure) and mechanical properties (i.e. stiffness, strength and failure mode) indicated that the multimodal scaffold had superior mechanical properties (Young's modulus ∼40 MPa and strength ∼1 MPa) in comparison with the controls, despite the large porosity (∼90% on average). A biological assessment was conducted with bone marrow stromal cell type (mesenchymal stem cells, mTERT-MSCs). While the new material compared favorably with the controls with respect to cell viability (on the outer surface), it outperformed them in terms of cell colonization within the scaffold. The latter result, which could neither be practically achieved in the controls nor expected based on current models of pore size distribution, demonstrated the greater openness of the pore structure of the bimodal material, which remarkably did not come at the expense of its mechanical properties. Furthermore, nanofibers were seen to form a nanoweb bridging across neighboring microfibers, which boosted cell motility and survival. Lastly, standard adipogenic and osteogenic differentiation tests served to demonstrate that the new scaffold did not hinder the multilineage potential of stem cells. © 2009 Acta Materialia Inc