Vertical Nanowire TFET Diameter Influence on Intrinsic Voltage Gain for Different Inversion Conditions

In this work, the impact of the nanowire TFET diameter on analog parameters in "weak" and "strong inversion" conditions is analyzed. Its relation with the current conduction mechanism is also studied. A comparison of the analog performance among TFETs doped with different source doping profile (abrupt and nonabrupt) and MOSFETs was experimentally realized for larger diameter nanowires. Additionally the TFET evaluation was extrapolated for smaller diameters by numerical simulation. The transistor efficiency and the Early voltage were considered in order to calculate the intrinsic voltage gain (AV). Both effects influence AV degradation for TFETs with smaller diameters biased in "weak inversion". While larger TFET nanowires show better AV than MOSFETs under "strong inversion" bias, narrower nanowires present potentialities for low power and low voltage applications, since their AV is better than the corresponding values for larger diameters TFET nanowires under "weak inversion" bias

Mast Cell Diseases in Practice and Research: Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond

Background: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. Objective: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patients’ quality of life by addressing unmet needs. Methods: In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. Results: Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. Conclusions: Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders.The authors thank Tania Bray, Jan Hempstead, Heather Mayne, Joanne Mulder-Brambleby, and Irene Wilson for their supporting contributions, and all patients and families affected by MCDs, who shared their needs and concerns for development of this project. Authors involved in study conception and design were P. Valent, S.V. Jennings, C.C. Finnerty, J.S. Hobart, M. Martín-Martínez, K.A. Sinclair, V.M. Slee, J. Agopian, C. Akin, I. Álvarez-Twose, P. Bonadonna, A.A. Bowman, K. Brockow, H. Bumbea, C. de Haro, J.S. Fok, K. Hartmann, N. Hegmann, O. Hermine, M. Kalisiak, C.H. Katelaris, J. Kurz, P. Marcis, D. Mayne, D. Mendoza, A. Moussy, G. Mudretzkyj, N. Nidelea Vaia, M. Niedoszytko, H. Oude Elberink, A. Orfao, D.H. Radia, S. Rosenmeier, E. Ribada, W. Schinhofen, J. Schwaab, F. Siebenhaar, M. Triggiani, G. Tripodo, R. Velazquez, Y. Wielink, F. Wimazal, T. Yigit, and C. Zubrinich. Authors involved in acquisition and review of data were S.V. Jennings, C.C. Finnerty, J.S. Hobart, M. Martín-Martínez, K.A. Sinclair, V.M. Slee, J. Agopian, C. Akin, I. Álvarez-Twose, P. Bonadonna, A.A. Bowman, K. Brockow, H. Bumbea, C. de Haro, J.S. Fok, K. Hartmann, N. Hegmann, O. Hermine, M. Kalisiak, C.H. Katelaris, J. Kurz, P. Marcis, D. Mayne, D. Mendoza, A. Moussy, G. Mudretzkyj, N. Nidelea Vaia, M. Niedoszytko, H. Oude Elberink, A. Orfao, D.H. Radia, S. Rosenmeier, E. Ribada, W. Schinhofen, J. Schwaab, F. Siebenhaar, M. Triggiani, G. Tripodo, R. Velazquez, Y. Wielink, F. Wimazal, T. Yigit, C. Zubrinich, and P. Valent. The Core Group (analysis and interpretation of data and drafting of the manuscript) include S.V. Jennings, C.C. Finnerty, J.S. Hobart, M. Martín-Martínez, K.A. Sinclair, and V.M. Slee. Critical revision was performed by S.V. Jennings, C.C. Finnerty, J.S. Hobart, M. Martín-Martínez, K.A. Sinclair, V.M. Slee, J. Agopian, C. Akin, I. Álvarez-Twose, P. Bonadonna, A.A. Bowman, K. Brockow, H. Bumbea, C. de Haro, J.S. Fok, K. Hartmann, N. Hegmann, O. Hermine, M. Kalisiak, C.H. Katelaris, J. Kurz, P. Marcis, D. Mayne, D. Mendoza, A. Moussy, G. Mudretzkyj, N. Nidelea Vaia, M. Niedoszytko, H. Oude Elberink, A. Orfao, D.H. Radia, S. Rosenmeier, E. Ribada, W. Schinhofen, J. Schwaab, F. Siebenhaar, M. Triggiani, G. Tripodo, R. Velazquez, Y. Wielink, F Wimazal, T. Yigit, C. Zubrinich, and P. Valent

HIV-1 Nef Employs Two Distinct Mechanisms to Modulate Lck Subcellular Localization and TCR Induced Actin Remodeling

The Nef protein acts as critical factor during HIV pathogenesis by increasing HIV replication in vivo via the modulation of host cell vesicle transport and signal transduction processes. Recent studies suggested that Nef alters formation and function of immunological synapses (IS), thereby modulating exogenous T-cell receptor (TCR) stimulation to balance between partial T cell activation required for HIV-1 spread and prevention of activation induced cell death. Alterations of IS function by Nef include interference with cell spreading and actin polymerization upon TCR engagement, a pronounced intracellular accumulation of the Src kinase Lck and its reduced IS recruitment. Here we use a combination of Nef mutagenesis and pharmacological inhibition to analyze the relative contribution of these effects to Nef mediated alterations of IS organization and function on TCR stimulatory surfaces. Inhibition of actin polymerization and IS recruitment of Lck were governed by identical Nef determinants and correlated well with Nef's association with Pak2 kinase activity. In contrast, Nef mediated Lck endosomal accumulation was separable from these effects, occurred independently of Pak2, required integrity of the microtubule rather than the actin filament system and thus represents a distinct Nef activity. Finally, reduction of TCR signal transmission by Nef was linked to altered actin remodeling and Lck IS recruitment but did not require endosomal Lck rerouting. Thus, Nef affects IS function via multiple independent mechanisms to optimize virus replication in the infected host

Common genetic variants contribute to risk of transposition of the great arteries

Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. Objective: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. Methods and Results: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. Conclusions: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus

Comparison between nMOS and pMOS Omega-gate nanowire down to 10nm width as a function of back gate bias

International audienceThis paper presents a comparison between nMOS and pMOS Omega-Gate Nanowire for different channel width (W-NW) down to 10 nm as a function of the large back gate bias variation (from +20 to -20 V) experimentally and by simulation. The main digital and analog parameters are analyzed in these devices as threshold voltage, subthreshold swing (SS), transconductance, transistor efficiency, Early Voltage and intrinsic voltage gain for transistor channel width from 220 nm down to 10 nm. It is shown that narrow channel devices (W-NW = 10 nm) present a small variation on the analyzed parameters as a function of back gate voltage due to stronger electrostatic control between gate and channel considering that they are effectively working like a gate-all-around devices. In general, all the nMOS parameters presents better results compared to pMOS due to the mobility enhancements. For wider devices (W-NW = 220 nm), it depends on the back interface condition. For a large enough back gate bias that tends to create a back interface conduction (+20 V for nMOS and -20 V for pMOS), the SS degrades from 61 mV dec(-1) (W-NW = 10 nm) to 68 mV dec(-1) (W-NW = 220 nm). However for a large enough back gate bias that induces a non-conduction region (tends to accumulation) at back interface (-20 V for nMOS and +20 V for pMOS) the SS changes from 60 to 62 mV dec(-1) at the same W-NW range, which is a very acceptable results. Additionally, the drain current (I-ON) and transconductance (linear and saturation regions) increase for this back gate bias condition (tends to accumulation), working almost like a pseudo nanosheet device for these parameters, avoiding also the parasitic conduction at the back interface. However, in spite of the intrinsic voltage gain is almost independent of the back gate bias, it improves of at least 10 dB for narrow devices due to the higher Early voltage and almost similar transistor efficiency than the wider ones