Complete positivity and thermodynamics in a driven open quantum system

While it is well known that complete positivity guarantees the fulfilment of the second law of thermodynamics, its possible violations have never been proposed as a check of the complete positivity of a given open quantum dynamics. We hereby consider an open quantum micro-circuit, effectively describable as a two-level open quantum system, whose asymptotic current might be experimentally accessible. This latter could indeed be used to discriminate between its possible non-completely positive Redfield dynamics and a completely positive one obtained by standard weak-coupling limit techniques, at the same time verifying the fate of the second law of thermodynamics in such a context.Comment: 28 pages, 8 figures, LaTe

Implications of non-Markovian quantum dynamics for the Landauer bound

We study the dynamics of a spin-1/2 particle interacting with a multi-spin environment, modelling the corresponding open system dynamics through a collision-based model. The environmental particles are prepared in individual thermal states, and we investigate the effects of a distribution of temperatures across the spin environment on the evolution of the system, particularly how thermalisation in the long-time limit is affected. We study the phenomenology of the heat exchange between system and environment and consider the information-to-energy conversion process, induced by the system-environment interaction and embodied by the Landauer principle. Furthermore, by considering an interacting-particles environment, we tune the dynamics of the system from an explicit Markovian evolution up to a strongly non-Markovian one, investigating the connections between non-Markovianity, the establishment of system-environment correlations, and the breakdown of the validity of Landauer principle

Role of the variety and some environmental factors on grape stilbenes

V. vinifera L. 'Barbera', 'Croatina', 'Malvasia di Candia aromatica', growing in the Piacenza viticultural area (North-West Italy) at four elevations (150, 240, 320, 420 m a.s.l.), were tested at harvest for grape stilbene (trans-resveratrol, trans-piceid, cis-piceid) synthesis over three years (2000-2002). Meteorological data were recorded, as well as vine production and fruit quality parameters. The most significant findings were:trans-piceid was the most abundantly produced stilbene compound (103 μg·kg-1 berry FW), while trans-resveratrol was the least produced (57 μg·kg-1 berry FW);'Barbera' and 'Croatina' had similar trans-resveratrol berry levels (71 μg·kg-1 berry FW and 76 μg·kg-1 berry FW respectively), higher than 'Malvasia di Candia aromatica' (24 μg·kg-1 berry FW);'Barbera' had the highest trans-piceid and cis-piceid concentrations (235 and 136 μg·kg-1 berry FW, respectively) while 'Malvasia di Candia aromatica' had the lowest levels (13 and 1 μg·kg-1 berry FW, respectively);stilbenes increased with elevation up to 320 m, while decreasing at the highest altitude;the vintage year only significantly affected the cis-piceid berry concentration which was positively related to the relative humidity at the end of ripening, and negatively related to degree-days at the end of ripening.

Tumor necrosis factor-alpha regulates the expression of inducible costimulator receptor ligand on CD34+ progenitor cells during differentiation into antigen presenting cells

The inducible costimulator receptor (ICOS) is a third member of the CD28 receptor family that regulates T cell activation and function. ICOS binds to a newly identified ligand on antigen presenting cells different from the CD152 ligands CD80 and CD86. We used soluble ICOSIg and a newly developed murine anti-human ICOS ligand (ICOSL) monoclonal antibody to further characterize the ICOSL during ontogeny of antigen presenting cells. In a previous study, we found that ICOSL is expressed on monocytes, dendritic cells, and B cells. To define when ICOSL is first expressed on myeloid antigen presenting cells, we examined ICOSL expression on CD34 cells in bone marrow. We found that CD34bright cells regardless of their myeloid commitment were ICOSL , whereas ICOSL was first expressed when CD34 expression diminished and the myeloid marker CD33 appeared

Effect of nitrogen supply on trans-resveratrol concentration in berries of Vitis vinifera L. cv. Cabernet Sauvignon

Research Note

Multiple myeloma cells alter the senescence phenotype of bone marrow mesenchymal stromal cells under participation of the DLK1-DIO3 genomic region

Background: Alterations and senescence in bone marrow mesenchymal stromal cells of multiple myeloma patients (MM-BMMSCs) have become an important research focus. However the role of senescence in the pathophysiology of MM is not clear. Methods: Correlation between senescence, cell cycle and microRNA expression of MM-BMMSCs (n = 89) was analyzed. Gene expression analysis, copy number analysis and methylation specific PCR were performed by Real-Time PCR. Furthermore, cyclin E1, cyclin D1, p16 and p21 genes were analyzed at the protein level using ELISA. Cell cycle and senescence were analyzed by FACS. MiRNA transfection was performed with miR-485-5p inhibitor and mimic followed by downstream analysis of senescence and cell cycle characteristics of MM-BMMSCs. Results were analyzed by Mann-Whitney U test, Wilcoxon signed-rank test and paired t-test depending on the experimental set up. Results: MM-BMMSCs displayed increased senescence associated beta-galactosidase activity (SA-betaGalA), cell cycle arrest in S phase and overexpression of microRNAs. The overexpressed microRNAs miR-485-5p and miR-519d are located on DLK1-DIO3 and C19MC, respectively. Analyses revealed copy number accumulation and hypomethylation of both clusters. KMS12-PE myeloma cells decreased SA-betaGalA and influenced cell cycle characteristics of MM-BMMSCs. MiR-485-5p was significantly decreased in co-cultured MM-BMMSCs in connection with an increased methylation of DLK1-DIO3. Modification of miR-485-5p levels using microRNA mimic or inhibitor altered senescence and cell cycle characteristics of MM-BMMSCs. Conculusions: Here, we show for the first time that MM-BMMSCs have aberrant methylation and copy number of the DLK1-DIO3 and C19MC genomic region. Furthermore, this is the first study pointing that multiple myeloma cells in vitro reduce both the senescence phenotype of MM-BMMSCs and the expression of miR-223 and miR-485-5p. Thus, it is questionable whether senescence of MM-BMMSCs plays a pathological role in active multiple myeloma or is more important when cell interaction with myeloma cells is inhibited. Furthermore, we found that MiR-485-5p, which is located on the DLK1-DIO3 cluster, seems to participate in the regulation of senescence status and cell cycle characteristics of MM-BMMSCs. Thus, further exploration of the microRNAs of DLK1-DIO3 could provide further insights into the origin of the senescence state and its reversal in MM-BMMSCs

Immunomodulatory molecules in renal cell cancer: CD80 and CD86 are expressed on tumor cells

Despite modern therapies with tyrosine kinase inhibitors (TKI), the management of patients with metastatic renal cell carcinoma (mRCC) remains a challenge. Significant immunosuppression has been described in patients with mRCC. Therefore, immunotherapeutic strategies such as checkpoint inhibitors have been developed. To further elucidate the underlying mechanisms of immunosuppression and response by therapy, different features of the immune microenvironment (expression of HIF-1-{alpha}, VEGFR-1, FOXP3, TGF-{beta}1, CD80, CD86, PD-1, and PD-L1) were analyzed in tumor tissues within different subgroups of mRCC patients (responders vs. non-responders to therapy). Results: The most interesting finding was low level CD80 and CD86-expression on tumor tissue samples (n = 18) of nearly all mRCC patients. This finding was in line with CD86 expression, which could also be found in renal carcinoma cell lines. To the best of our knowledge, this is the first report on CD820/CD86 expression in human renal cell carcinoma-possibility reflecting an immunomodulatory mechanism of the tumor

Phase II trial of temsirolimus for relapsed/refractory primary CNS lymphoma

Purpose: In this phase II study (NCT00942747), temsirolimus was tested in patients with relapsed or refractory primary CNS lymphoma (PCNSL). Patients and Methods: Immunocompetent adults with histologically confirmed PCNSL after experiencing high-dose methotrexate-based chemotherapy failure who were not eligible for or had experienced high-dose chemotherapy with autologous stem-cell transplant failure were included. The first cohort (n = 6) received 25 mg temsirolimus intravenously once per week. All consecutive patients received 75 mg intravenously once per week. Results: Thirty-seven eligible patients (median age, 70 years) were included whose median time since their last treatment was 3.9 months (range, 0.1 to 14.6 months). Complete response was seen in five patients (13.5%), complete response unconfirmed in three (8%), and partial response in 12 (32.4%) for an overall response rate of 54%. Median progression-free survival was 2.1 months (95% CI, 1.1 to 3.0 months). The most frequent Common Toxicity Criteria ≥ 3° adverse event was hyperglycemia in 11 (29.7%) patients, thrombocytopenia in eight (21.6%), infection in seven (19%), anemia in four (10.8%), and rash in three (8.1%). Fourteen blood/CSF pairs were collected in nine patients (10 pairs in five patients in the 25-mg cohort and four pairs in four patients in the 75-mg cohort). The mean maximum blood concentration was 292 ng/mL for temsirolimus and 37.2 ng/mL for its metabolite sirolimus in the 25-mg cohort and 484 ng/mL and 91.1 ng/mL, respectively, in the 75-mg cohort. Temsirolimus CSF concentration was 2 ng/mL in one patient in the 75-mg cohort; in all others, no drug was found in their CSF. Conclusion: Single-agent temsirolimus at a weekly dose of 75 mg was found to be active in relapsed/refractory patients with PCNSL; however, responses were usually short lived

CD20 and CD19 targeted vectors induce minimal activation of resting B lymphocytes

B lymphocytes are an important cell population of the immune system. However, until recently it was not possible to transduce resting B lymphocytes with retro- or lentiviral vectors, making them unsusceptible for genetic manipulations by these vectors. Lately, we demonstrated that lentiviral vectors pseudotyped with modified measles virus (MV) glycoproteins hemagglutinin, responsible for receptor recognition, and fusion protein were able to overcome this transduction block. They use either the natural MV receptors, CD46 and signaling lymphocyte activation molecule (SLAM), for cell entry (MV-LV) or the vector particles were further modified to selectively enter via the CD20 molecule, which is exclusively expressed on B lymphocytes (CD20-LV). It has been shown previously that transduction by MV-LV does not induce B lymphocyte activation. However, if this is also true for CD20-LV is still unknown. Here, we generated a vector specific for another B lymphocyte marker, CD19, and compared its ability to transduce resting B lymphocytes with CD20-LV. The vector (CD19ds-LV) was able to stably transduce unstimulated B lymphocytes, albeit with a reduced efficiency of about 10% compared to CD20-LV, which transduced about 30% of the cells. Since CD20 as well as CD19 are closely linked to the B lymphocyte activation pathway, we investigated if engagement of CD20 or CD19 molecules by the vector particles induces activating stimuli in resting B lymphocytes. Although, activation of B lymphocytes often involves calcium influx, we did not detect elevated calcium levels. However, the activation marker CD71 was substantially up-regulated upon CD20-LV transduction and most importantly, B lymphocytes transduced with CD20-LV or CD19ds-LV entered the G1b phase of cell cycle, whereas untransduced or MV-LV transduced B lymphocytes remained in G0. Hence, CD20 and CD19 targeting vectors induce activating stimuli in resting B lymphocytes, which most likely renders them susceptible for lentiviral vector transduction

Spontaneous non-sustained ventricular tachycardia and premature ventricular contractions and their prognostic relevance in patients with cancer in routine care

AIMS: It is largely unknown whether cancer patients seen in routine care show ventricular arrhythmias in 24 h electrocardiograms (ECGs), and whether when they are detected they carry prognostic relevance. METHODS AND RESULTS: We included 261 consecutive cancer patients that were referred to the department of cardiology for 24 h ECG examination and 35 healthy controls of similar age and sex in the analysis. To reduce selection bias, cancer patients with known left ventricular ejection fraction <45% were not included in the analysis. Non–sustained ventricular tachycardia (NSVT) episodes of either ≥3 and ≥4 beats duration were more frequent in cancer patients than controls (17% vs. 0%, p = 0.0008; 10% vs. 0%, p = 0.016). Premature ventricular contractions (PVCs)/24 h were not more frequent in cancer patients compared to controls (median (IQR), 26 (2–360) vs. 9 (1–43), p = 0.06; ≥20 PVCs 53% vs. 37%, p = 0.07). During follow-up, (up to 7.2 years, median 15 months) of the cancer patients, 158 (61%) died (1-/3-/5-year mortality rates: 45% [95%CI 39–51%], 66% [95%CI 59–73%], 73% [95%CI 64–82%]). Both non-sustained ventricular tachycardia of ≥4 beats and ≥20 PVCs/24 h independently predicted mortality in univariate and multivariate survival analyses, adjusted for all other univariate predictors of mortality as well as relevant clinical factors, including cancer stage and type, performance status (ECOG), prior potentially cardiotoxic anti-cancer drug therapy, coronary artery disease, potassium concentration, and haemoglobin (multivariate adjusted hazard ratios: NSVT ≥4 beats [HR 1.76, p = 0.022], ≥20 PVCs/24 h [HR 1.63, p < 0.0064]). CONCLUSIONS: NSVT ≥4 beats and ≥20 PVCs/day seen in routine 24 h ECGs of patients with cancer carry prognostic relevance