77 research outputs found
Hot-Carrier Degradation in Power LDMOS: Selective LOCOS-Versus STI-Based Architecture
In this paper, we present an analysis of the degradation induced by hot-carrier stress in new generation power lateral double-diffused MOS (LDMOS) transistors. Two architectures with the same nominal voltage and comparable performance featuring a selective LOCOS and a shallow-trench isolation are investigated by means of constant voltage stress measurements and TCAD simulations. In particular, the on-resistance degradation in linear regime is experimentally extracted and numerically reproduced under different stress conditions. A similar amount of degradation has been reached by the two architectures, although different physical mechanisms contribute to the creation of the interface states. By using a recently developed physics-based degradation model, it has been possible to distinguish the damage due to collisions of single high-energetic electrons (single-particle events) and the contribution of colder electrons impinging on the silicon/oxide interface (multiple-particle events). A clear dominance of the single-electron collisions has been found in the case of LOCOS structure, whereas the multiple-particle effect plays a clear role in STI-based device at larger gate-voltage stress
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Photolithographic bio-patterning of magnetic sensors for biomolecular recognition
In the last years, magnetoresistive biosensors arrays have drawn a great interest due to their high sensitivity and integrability in lab-on-chip platforms. In such devices, the selective functionalization of the sensor active area is a major issue, in order to achieve high sensitivity and quantification capability. Here, we present a straightforward photolithographic procedure to create patterns of bio-reactive polymer regions on the sensor's surface, with micrometric resolution. The effectiveness of the procedure in providing high specificity and improved sensor performance is demonstrated in the case of magnetoresistive biosensors based on magnetic tunneling junctions (MTJs). On-chip biomolecular recognition assays demonstrate an enhanced sensitivity in selectively functionalized sensors with respect to non-patterned sensors, eventually leading to a limit of detection below the pM range, without target pre-concentration or chemical amplification
Hot-carrier degradation in power LDMOS: Drain bias dependence and lifetime evaluation
In this brief, we present an analysis of the degradation induced by hot-carrier stress in new generation power lateral double-diffused MOSFET (LDMOS) transistors. When a relatively high drain voltage is applied during the ON-state regime, high energetic and/or multiple cold electrons are recognized as the main source of degradation affecting the LDMOS lifetime: The latter is usually extrapolated at typical operating drain voltages. Hence, the extrapolation criterion is particularly critical, and different models have been proposed in the past and discussed in this brief. In particular, the dependence of ON-resistance degradation (RON) on drain bias is investigated, and a simplified extrapolation model, accounting for the saturation effects of RON at long stress times, is proposed and validated by comparison with experiments and advanced physics-based TCAD simulations, confirming the ability to accurately estimate lifetime on devices featuring short-circuited source-body contacts
Functionalization of gold surfaces with copoly(DMA-NAS-MAPS) by dip coating: Surface characterization and hybridization tests
In this work, a new method to functionalize a gold surface by dip coating with a functional copolymer is presented. The coating procedure is simple, robust and can be accomplished in less than one hour. Atomic force microscopy (AFM) scratch tests reveal the presence of a homogeneous polymer coating with a thickness of 2.5nm. X-ray photoemission spectroscopy spectra from C1s, N1s and O1s levels present the typical fingerprints of the polymeric overlayer, i.e. the characteristic peaks from CNC   O and NC   O groups.
Surface plasmon resonance (SPR) binding assays were used to check the coating functional properties. Immobilization of heparin to SPR gold surfaces functionalized with copoly(DMA-NAS-MAPS)- followed by binding analysis with the well known heparin binding protein fibroblast growth factor 2 yield binding kinetic parameters comparable to those obtained with commercially available carboxymethyl dextran- functionalized sensorchips, thus confirming the great potential of the proposed technique
Lipid Abnormalities in HIV-Infected Patients Are Not Correlated With Lopinavir Plasma Concentrations
Early Impairment of Gut Function and Gut Flora Supporting a Role for Alteration of Gastrointestinal Mucosa in Human Immunodeficiency Virus Pathogenesisâ–¿
Our results show that impairment of the gastrointestinal tracts in human immunodeficiency virus (HIV)-positive patients is present in the early phases of HIV disease. This impairment is associated with alterations in gut microbiota and intestinal inflammatory parameters. These findings support the hypothesis that alterations at the gastrointestinal-tract level are a key factor in HIV pathogenesis
Statistical challenges in the anti-fraud analysis of Customs data
Customs Services collect large amount of data submitted by traders for the Customs clearance process. It is crucial for Customs administrations to dispose of instruments to analyse data and take decisions on applicable customs duties, shipments approval and anti-fraud investigations. The budget of the European Union relies in part on customs duties. For this reason, the EU Hercule Programme promotes and supports research activities with application to anti-fraud and the protection of the EU budget at large. This session will bring together experiences of Customs analysts and academic researchers that have addressed anti-fraud and customs data analysis from very different angles.JRC.I.3-Text and Data Minin
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