Functional Integral approach to time-dependent heat exchange in open quantum systems: general method and applications

We establish the path integral approach for the time-dependent heat exchange of an externally driven quantum system coupled to a thermal reservoir. We derive the relevant influence functional and present an exact formal expression for the moment generating functional which carries all statistical properties of the heat exchange process for general linear dissipation. The general method is applied to the time-dependent average heat transfer in the dissipative two-state system. We show that the heat can be written as a convolution integral which involves the population and coherence correlation functions of the two-state system and additional correlations due to a polarization of the reservoir. The corresponding expression can be solved in the weak-damping limit both for white noise and for quantum mechanical coloured noise. The implications of pure quantum effects are discussed. Altogether a complete description of the dynamics of the average heat transfer ranging from the classical regime down to zero temperature is achieved.Comment: 19 pages, 4 figure

Respiratory and non-respiratory outcomes of bronchopulmonary dysplasia in adolescents: A systematic review

Background: There is lack of evidence synthesis on the global consequences of bronchopulmonary dysplasia (BPD) in adolescence. Aim: Assess the impact of bronchopulmonary dysplasia on respiratory and non-respiratory outcomes in adolescents.Methods: A systematic review of studies assessing the outcomes of adolescents aged 10 to 19 years-old with BPD was conducted. We independently screened studies published until 6th March 2023 in PubMed (R) and Scopus (R) databases. Data on methodologic design, sample descriptive and findings were extracted from each study. Risk of bias was assessed using quality assessment tools.Results: Thirty-one studies were included. Adolescents with a history of BPD present with more respiratory symptoms (wheezing, respiratory exacerbations, need for respiratory medication) and twenty-five studies showed a reduction in pulmonary function, with varying impact according to BPD severity and no differences before and after the surfactant era. Spirometry evaluation throughout the years is not consensual, but meth-acholine and salbutamol response in BPD groups is increased compared to non-BPD groups. Markers of eosin-ophilic airway inflammation are not increased as in asthma patients. Exercise potential is identical, but data regarding physical capacity and activity are inconsistent. More frequent radiologic abnormalities translate into higher high-resolution computed tomography scores, with linear (72.2 %) and triangular subpleural opacities (58.3 %) as the most common findings. There is a higher risk for special needs in education, but quality of life seems to be equal to non-BPD adolescents.Conclusions: BPD negatively impacts both pulmonary and non-pulmonary outcomes in adolescents

Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade

In the last decade, the treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the introduction of immune checkpoint inhibitors (ICI) directed against programmed death protein 1 (PD-1) and its ligand (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA-4). In spite of these improvements, some patients do not achieve any benefit from ICI, and inevitably develop resistance to therapy over time. Tumor microenvironment (TME) might influence response to immunotherapy due to its prominent role in the multiple interactions between neoplastic cells and the immune system. Studies investigating lung cancer from the perspective of TME pointed out a complex scenario where tumor angiogenesis, soluble factors, immune suppressive/regulatory elements and cells composing TME itself participate to tumor growth. In this review, we point out the current state of knowledge involving the relationship between tumor cells and the components of TME in NSCLC as well as their interactions with immunotherapy providing an update on novel predictors of benefit from currently employed ICI or new therapeutic targets of investigational agents. In first place, increasing evidence suggests that TME might represent a promising biomarker of sensitivity to ICI, based on the presence of immune-modulating cells, such as Treg, myeloid derived suppressor cells, and tumor associated macrophages, which are known to induce an immunosuppressive environment, poorly responsive to ICI. Consequently, multiple clinical studies have been designed to influence TME towards a pro-immunogenic state and subsequently improve the activity of ICI. Currently, the mostly employed approach relies on the association of \u201cclassic\u201d ICI targeting PD-1/PD-L1 and novel agents directed on molecules, such as LAG-3 and TIM-3. To date, some trials have already shown promising results, while a multitude of prospective studies are ongoing, and their results might significantly influence the future approach to cancer immunotherapy

Type-Decomposition of a Pseudo-Effect Algebra

The theory of direct decomposition of a centrally orthocomplete effect algebra into direct summands of various types utilizes the notion of a type-determining (TD) set. A pseudo-effect algebra (PEA) is a (possibly) noncommutative version of an effect algebra. In this article we develop the basic theory of centrally orthocomplete PEAs, generalize the notion of a TD set to PEAs, and show that TD sets induce decompositions of centrally orthocomplete PEAs into direct summands.Comment: 18 page

Symptomatic carotid atherosclerotic plaques are associated with increased infiltration of natural killer (NK) cells and higher serum levels of NK activating receptor ligands

A wide array of immune cells, including lymphocytes, is known to be present and to play a pathogenetic role in atherosclerotic lesions. However, limited information is currently available regarding the presence of Natural Killer (NF cell subsets within vessel plaque, and more in general, regarding their role in human atherosclerosis. We evaluated the distribution of NK cells in human carotid atherosclerotic plaques, dissecting asymptomatic and symptomatic patients (identified as affected by stroke, transient ischemic attack, or amaurosis fugax within 6 months) with the aim of shedding light on the putative contribution of NK cells to the pathogenic process that leads to plaque instability and subsequent clinical complications. We observed that carotid plaques were consistently infiltrated by NK cells and, among them, CD56(bright)perforin(low) NK cells were abundantly present and displayed different markers of tissue residency (i.e., CD103 CD69 and CD49a). Interestingly, carotid atherosclerotic plaques of symptomatic patients showed a higher content of NK cells and an increased ratio between CD56(bright)perforin(low) NK cells and their CD56(dim)perforin(high)counterpart. NK cells isolated from plaques of symptomatic patients were also stronger producers of IFN-gamma. Analysis of the expression of NK activating receptor ligands (including MICA/B, ULBP-3, and B7-H6) in atherosclerotic carotid plaques revealed that they were abundantly expressed by a HLA-DR(+)CD11c(+) myeloid cell population resident in the plaques. Remarkably, sera of symptomatic patients contained significant higher levels of soluble ligands for NK activating receptors. Our observations indicate that CD56(bright)( )NK cells accumulate within human atherosclerotic lesions and suggest a possible contribution of NK cells to the process determining plaque instability

Plasmons in layered structures including graphene

We investigate the optical properties of layered structures with graphene at the interface for arbitrary linear polarization at finite temperature including full retardation by working in the Weyl gauge. As a special case, we obtain the full response and the related dielectric function of a layered structure with two interfaces. We apply our results to discuss the longitudinal plasmon spectrum of several single and double layer devices such as systems with finite and zero electronic densities. We further show that a nonhomogeneous dielectric background can shift the relative weight of the in-phase and out-of-phase mode and discuss how the plasmonic mode of the upper layer can be tuned into an acoustic mode with specific sound velocity.Comment: 18 pages, 6 figure

Spectral noise for edge states at filling factor ν=5/2\nu=5/2

We present a detailed analysis of finite frequency noise for the $\nu=5/2$ fractional quantum Hall state in a quantum point contact geometry. The results are obtained within the Pfaffian and anti-Pfaffian models. We show that the behaviour of the coloured noise allows unambigously to discriminate among tunneling excitations with different charges. Optimal values of the external bias are found in order to emphasize the visibility of the noise peak associated with the tunneling of a 2-agglomerate, namely an excitation with charge double of the fundamental one. These correspond to the regime in which the bias is larger than the neutral modes cut-off frequency. The dependence on the temperature is also investigated in order to discriminate between the considered models.Comment: 14 pages, 4 figures. Submitted to New Journal of Phyisc

The Immune Inhibitory Receptor LAIR-1 Is Highly Expressed by Plasmacytoid Dendritic Cells and Acts Complementary with NKp44 to Control IFNα Production

Plasmacytoid dendritic cells (pDCs) are a subset of dendritic cells endowed with the capacity of producing large amounts of IFNα. Here we show that the Leukocyte-Associated Ig-like Receptor-1 (LAIR-1) is abundantly expressed on pDCs (the highest expression among all leukocytes) and its cross-linking inhibits IFNα production in response to Toll-like receptor ligands. Remarkably, LAIR-1 expression in pDCs is down-regulated in the presence of interleukin (IL)-3, thus indicating coordinated functions with NKp44, another pDC inhibitory receptor, which is conversely induced by IL-3. Nevertheless, the expression of NKp44 in pDCs isolated from secondary lymphoid organs, which is thought to be influenced by IL-3, is not coupled to a decreased expression of LAIR-1. Interestingly, pDCs isolated from peripheral blood of systemic lupus erithematosus (SLE) patients express lower levels of LAIR-1 while displaying slight but consistent expression of NKp44, usually undetectable on pDCs derived from healthy donors. Using sera derived from SLE patients, we show that LAIR-1 and NKp44 display synergistic inhibitory effects on IFNα production by interleukin IL-3 cultured pDCs stimulated with DNA immunocomplexes. In conclusion, our results indicate that the inhibitory function of LAIR-1 may play a relevant role in the mechanisms controlling IFNα production by pDCs both in normal and pathological innate immune responses

Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity

<p>Abstract</p> <p>Background</p> <p>Tumour growth and metastatic infiltration are favoured by several components of the tumour microenvironment. Bone marrow-derived multipotent mesenchymal stromal cells (MSC) are known to contribute to the tumour stroma. When isolated from healthy bone marrow, MSC exert potent antiproliferative effects on immune effector cells. Due to phenotypic and morphological similarities of MSC and tumour stromal cells (TStrC), we speculated that immunotherapeutic approaches may be hampered if TStrC may still exhibit immunomodulatory properties of MSC.</p> <p>Methods</p> <p>In order to compare immunomodulatory properties of MSC and tumour stromal cells (TStrC), we established and analyzed TStrC cultures from eleven paediatric tumours and MSC preparations from bone marrow aspirates. Immunophenotyping, proliferation assays and NK cell cytotoxicity assays were employed to address the issue.</p> <p>Results</p> <p>While TStrC differed from MSC in terms of plasticity, they shared surface expression of CD105, CD73 and other markers used for MSC characterization. Furthermore, TStrC displayed a strong antiproliferative effect on peripheral blood mononuclear cells (PBMC) in coculture experiments similar to MSC. NK cell cytotoxicity was significantly impaired after co-culture with TStrC and expression of the activating NK cell receptors NKp44 and NKp46 was reduced.</p> <p>Conclusions</p> <p>Our data show that TStrC and MSC share important phenotypic and functional characteristics. The inhibitory effect of TStrC on PBMC and especially on NK cells may facilitate the immune evasion of paediatric tumours.</p

Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients

Activity of cetuximab, a chimeric monoclonal antibody targeting the epidermal growth factor receptor, is largely attributed to its direct antiproliferative and proapoptotic effects. Antibody-dependent cell-mediated cytotoxicity (ADCC) could be another possible mechanism of cetuximab antitumor effects and its specific contribution on the clinical activity of cetuximab is unknown.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe