Design and Fabrication of Terahertz Metallic Gratings on a Two-Wire Waveguide

In this study, we present the design, fabrication and experimental characterization of waveguide-integrated gratings operating at THz frequencie

Symmetric Vlasov-type antenna for High Power Microwave applications

We present a novel Vlasov-type antenna operating at 2.5 GHz and composed of a circular waveguide with a double bevel-cut. Simulation results show that the proposed antenna is capable of providing a wider emission angle if compared to standard Vlasov configurations, while still maintaining an adequate gain level. For this reason, it could be of interest for those High-Power Microwave (HPM) applications in which a larger area need to be covered by the EM field

Stability of laser cavity-solitons for metrological applications

Laser cavity-solitons can appear in systems comprised of a nonlinear microcavity nested within an amplifying fiber loop. These states are robust and self-emergent and constitute an attractive class of solitons that are highly suitable for microcomb generation. Here, we present a detailed study of the free-running stability properties of the carrier frequency and repetition rate of single solitons, which are the most suitable states for developing robust ultrafast and high repetition rate comb sources. We achieve free-running fractional stability on both optical carrier and repetition rate (i.e., 48.9 GHz) frequencies on the order of 10^-9 for a 1 s gate time. The repetition rate results compare well with the performance of state-of-the-art (externally driven) microcomb sources, and the carrier frequency stability is in the range of performance typical of modern free-running fiber lasers. Finally, we show that these quantities can be controlled by modulating the laser pump current and the cavity length, providing a path for active locking and long-term stabilization

Targeting prostate cancer based on signal transduction and cell cycle pathways

Prostate cancer remains a leading cause of death in men despite increased capacity to diagnose at earlier stages. After prostate cancer has become hormone independent, which often occurs after hormonal ablation therapies, it is difficult to effectively treat. Prostate cancer may arise from mutations and dysregulation of various genes involved in regulation signal transduction (e.g., PTEN, Akt, etc.,) and the cell cycle (e.g., p53, p21Cip1, p27Kip1, Rb, etc.,). This review focuses on the aberrant interactions of signal transduction and cell cycle genes products and how they can contribute to prostate cancer and alter therapeutic effectiveness. Originally published Cell Cycle, Vol. 7, No. 12, June 200

Targeting the leukemic stem cell: the Holy Grail of leukemia therapy

Since the discovery of leukemic stem cells (LSCs) over a decade ago, many of their critical biological properties have been elucidated, including their distinct replicative properties, cell surface phenotypes, their increased resistance to chemo-therapeutic drugs and the involvement of growthpromoting chromosomal translocations. Of particular importance is their ability to transfer malignancy to non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. Furthermore, numerous studies demonstrate that acute myeloid leukemia arises from mutations at the level of stem cell, and chronic myeloid leukemia is also a stem cell disease. In this review, we will evaluate the main characteristics of LSCs elucidated in several well-documented leukemias. In addition, we will discuss points of therapeutic intervention. Promising therapeutic approaches include the targeting of key signal transduction pathways (for example, PI3K, Rac and Wnt) with smallmolecule inhibitors and specific cell surface molecules (for example, CD33, CD44 and CD123), with effective cytotoxic antibodies. Also, statins, which are already widely therapeutically used for a variety of diseases, show potential in targeting LSCs. In addition, drugs that inhibit ATP-binding cassette transporter proteins are being extensively studied, as they are important in drug resistance â a frequent characteristic of LSCs. Although the specific targeting of LSCs is a relatively new field, it is a highly promising battleground that may reveal the Holy Grail of cancer therapy. Originally published Leukemia, Vol. 23, No. 1, Jan 200

Ticagrelor, but not clopidogrel, reduces arterial thrombosis via endothelial tissue factor suppression

The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with focus on arterial thrombosis and its key trigger tissue factor have not been previously investigated.Methods and results: Human aortic endothelial cells were treated with ticagrelor or clopidogrel active metabolite (CAM) and stimulated with tumour necrosis factor-alpha (TNF-α); effects on procoagulant tissue factor (TF) expression and activity, its counter-player TF pathway inhibitor (TFPI) and the underlying mechanisms were determined. Further, arterial thrombosis by photochemical injury of the common carotid artery, and TF expression in the murine endothelium were examined in C57BL/6 mice treated with ticagrelor or clopidogrel. Ticagrelor, but not CAM, reduced TNF-α-induced TF expression via proteasomal degradation and TF activity, independently of the P2Y12 receptor and the equilibrative nucleoside transporter 1 (ENT1), an additional target of ticagrelor. In C57BL/6 mice, ticagrelor prolonged time to arterial occlusion, compared with clopidogrel, despite comparable antiplatelet effects. In line with our in vitro results, ticagrelor, but not clopidogrel, reduced TF expression in the endothelium of murine arteries.Conclusion: Ticagrelor, unlike clopidogrel, exhibits endothelial-specific antithrombotic properties and blunts arterial thrombus formation. The additional antithrombotic properties displayed by ticagrelor may explain its greater efficacy in reducing thrombotic events in clinical trials. These findings may provide the basis for new indications for ticagrelor

Roles of the RAF/MEK/ERK Pathway in Cell Growth, Malignant Transformation and Drug Resistance

Growth factors and mitogens use the Ras/Raf/MEK/ERK signaling cascade to transmit signals from their receptors to regulate gene expression and prevent apoptosis. Some components of these pathways are mutated or aberrantly expressed in human cancer (e.g., Ras, B-Raf). Mutations also occur at genes encoding upstream receptors (e.g., EGFR and Flt-3) and chimeric chromosomal translocations (e.g., BCR-ABL) which transmit their signals through these cascades. Even in the absence of obvious genetic mutations, this pathway has been reported to be activated in over 50% of acute myelogenous leukemia and acute lymphocytic leukemia and is also frequently activated in other cancer types (e.g., breast and prostate cancers). Importantly, this increased expression is associated with a poor prognosis. The Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt pathways interact with each other to regulate growth and in some cases tumorigenesis. For example, in some cells, PTEN mutation may contribute to suppression of the Raf/MEK/ERK cascade due to the ability of activated Akt to phosphorylate and inactivate different Rafs. Although both of these pathways are commonly thought to have anti-apoptotic and drug resistance effects on cells, they display different cell lineage specific effects. For example, Raf/MEK/ERK is usually associated with proliferation and drug resistance of hematopoietic cells, while activation of the Raf/MEK/ERK cascade is suppressed in some prostate cancer cell lines which have mutations at PTEN and express high levels of activated Akt. Furthermore the Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt pathways also interact with the p53 pathway. Some of these interactions can result in controlling the activity and subcellular localization of Bim, Bak, Bax, Puma and Noxa. Raf/MEK/ERK may promote cell cycle arrest in prostate cells and this may be regulated by p53 as restoration of wild-type p53 in p53 deficient prostate cancer cells results in their enhanced sensitivity to chemotherapeutic drugs and increased expression of Raf/MEK/ERK pathway. Thus in advanced prostate cancer, it may be advantageous to induce Raf/MEK/ERK expression to promote cell cycle arrest, while in hematopoietic cancers it may be beneficial to inhibit Raf/MEK/ERK induced proliferation and drug resistance. Thus the Raf/MEK/ERK pathway has different effects on growth, prevention of apoptosis, cell cycle arrest and induction of drug resistance in cells of various lineages which may be due to the presence of functional p53 and PTEN and the expression of lineage specific factors. Originally published Biochim Biophys Acta, Vol. 1773, No. 8, August 200

Impact of SARS-CoV-2 Pandemic and Strategies for Resumption of Activities During the Second Wave of the Pandemic : A Report From Eight Paediatric Hospitals From the ECHO Network

The Severe Acute Respiratory Syndrome CoronaVirus type 2 (SARS-CoV-2) pandemic impacted the organization of paediatric hospitals. This study aimed to evaluate the preparedness for the pandemic among a European network of children's hospitals and to explore the strategies to restart health care services. A cross-sectional, web-based survey was distributed in May 2020 to the 13 children's tertiary care hospitals belonging to the European Children's Hospitals Organisation. Responses were obtained from eight hospitals (62%). Significant reductions were observed in accesses to the emergency departments (41.7%), outpatient visits (35.7%), intensive and non-intensive care unit inpatient admissions (16.4 and 13%, respectively) between February 1 and April 30, 2020 as compared with the same period of 2019. Overall, 93 children with SARS CoV-2 infection were admitted to inpatient wards. All the hospitals created SARS-CoV-2 preparedness plans for the diagnosis and management of infected patients. Routine activities were re-scheduled. Four hospitals shared their own staff with adult units, two designated bed spaces for adults and only one admitted adults to inpatient wards. The three main components for the resumption of clinical activities were testing, source control, and reorganization of spaces and flows. Telemedicine and telehealth services were used before the SARS-CoV-2 pandemic by three hospitals and by all the hospitals during it. Conclusion: The present study provides a perspective on preparedness to SARS-CoV-2 pandemic among eight large European children's hospitals, on the impact of the pandemic on the hospital activities and on the strategies adopted to restart clinical activities.Peer reviewe