Development of Lumped Element Kinetic Inductance Detectors for the W-Band

We are developing a Lumped Element Kinetic Inductance Detector (LEKID) array able to operate in the W-band (75-110 GHz) in order to perform ground-based Cosmic Microwave Background (CMB) and mm-wave astronomical observations. The W-band is close to optimal in terms of contamination of the CMB from Galactic synchrotron, free-free, and thermal interstellar dust. In this band, the atmosphere has very good transparency, allowing interesting ground-based observations with large (>30 m) telescopes, achieving high angular resolution (<0.4 arcmin). In this work we describe the startup measurements devoted to the optimization of a W-band camera/spectrometer prototype for large aperture telescopes like the 64 m SRT (Sardinia Radio Telescope). In the process of selecting the best superconducting film for the LEKID, we characterized a 40 nm thick Aluminum 2-pixel array. We measured the minimum frequency able to break CPs (i.e. $h\nu=2\Delta\left(T_{c}\right)=3.5k_{B}T_{c}$) obtaining $\nu=95.5$ GHz, that corresponds to a critical temperature of 1.31 K. This is not suitable to cover the entire W-band. For an 80 nm layer the minimum frequency decreases to 93.2 GHz, which corresponds to a critical temperature of 1.28 K; this value is still suboptimal for W-band operation. Further increase of the Al film thickness results in bad performance of the detector. We have thus considered a Titanium-Aluminum bi-layer (10 nm thick Ti + 25 nm thick Al, already tested in other laboratories), for which we measured a critical temperature of 820 mK and a cut-on frequency of 65 GHz: so this solution allows operation in the entire W-band.Comment: 16th International Workshop on Low Temperature Detectors, Grenoble 20-24 July 2015, Journal of Low Temperature Physics, Accepte

Stereopsis in sports: Visual skills and visuomotor integration models in professional and non-professional athletes

Visual skills in sport are considered relevant variables of athletic performance. However, data on the specific contribution of stereopsis—as the ability to perceive depth—in sport performance are still scarce and scattered in the literature. The aim of this review is therefore to take stock of the effects of stereopsis on the athletic performance, also looking at the training tools to improve visual abilities and potential differences in the visuomotor integration processes of professional and non-professional athletes. Dynamic stereopsis is mainly involved in catching or interceptive actions of ball sports, whereas strategic sports use different visual skills (peripheral and spatial vision) due to the sport-specific requirements. As expected, professional athletes show better visual skills as compared to non-professionals. However, both non-professional and professional athletes should train their visual skills by using sensory stations and light boards systems. Non-professional athletes use the visual inputs as the main method for programming motor gestures. In contrast, professional athletes integrate visual information with sport expertise, thus, they encode the match (or the athletic performance) through a more complex visuomotor integration system. Although studies on visual skills and stereopsis in sports still appear to be in their early stages, they show a large potential for both scientific knowledge and technical development

Efficacy of Bevacizumab-Capecitabine in Combination for the First-Line Treatment of Metastatic Breast Cancer

There is an ongoing need for development of new chemotherapeutic regimens for metastatic breast cancer [mBC], especially when tumors lack therapeutic targets such as the estrogen or progesterone receptor [ER/PR], or the human epidermal growth factor receptor-2 [HER2]. Capecitabine is an orally bioavailable fluoropyrimidine approved for monotherapy in mBC, and bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor which has shown to be active in mBC and tolerable in combination with other chemotherapeutics. The combination of these two agents has been explored in multiple phase II and III clinical studies, with improvements in progression-free survival and overall response rates noted as compared to capecitabine monotherapy. However, the use of bevacizumab in combination with capecitabine and other chemotherapy agents for mBC remains beset with controversy due to safety concerns, cost issues, and pending regulatory decisions

Thyroid-specific transcription factors control Hex promoter activity

The homeobox-containing gene Hex is expressed in several cell types, including thyroid follicular cells, in which it regulates the transcription of tissue-specific genes. In this study the regulation of Hex promoter activity was investigated. Using co-transfection experiments, we demonstrated that the transcriptional activity of the Hex gene promoter in rat thyroid FRTL-5 cells is ∼10-fold greater than that observed in HeLa and NIH 3T3 cell lines (which do not normally express the Hex gene). To identify the molecular mechanisms underlying these differences, we evaluated the effect of the thyroid-specific transcription factor TTF-1 on the Hex promoter activity. TTF-1 produced 3-4-fold increases in the Hex promoter activity. Gel-retardation assays and mutagenesis experiments revealed the presence of functionally relevant TTF-1 binding sites in the Hex promoter region. These in vitro data may also have functional relevance in vivo, since a positive correlation between TTF-1 and Hex mRNAs was demonstrated in human thyroid tissues by means of RT-PCR analysis. The TTF-1 effect, however, is not sufficient to explain the difference in Hex promoter activity between FRTL-5 and cells that do not express the Hex gene. For this reason, we tested whether Hex protein is able to activate the Hex promoter. Indeed, co-transfection experiments indicate that Hex protein is able to increase the activity of its own promoter in HeLa cells ∼4-fold. TTF-1 and Hex effects are additive: when transfected together in HeLa cells, the Hex promoter activity is increased 6-7-fold. Thus, the contemporary presence of both TTF-1 and Hex could be sufficient to explain the higher transcriptional activity of the Hex promoter in thyroid cells with respect to cell lines that do not express the Hex gene. These findings demonstrate the existence of direct cross-regulation between thyroid-specific transcription factors

Kinetic Inductance Detectors for the OLIMPO experiment: design and pre-flight characterization

We designed, fabricated, and characterized four arrays of horn--coupled, lumped element kinetic inductance detectors (LEKIDs), optimized to work in the spectral bands of the balloon-borne OLIMPO experiment. OLIMPO is a 2.6 m aperture telescope, aimed at spectroscopic measurements of the Sunyaev-Zel'dovich (SZ) effect. OLIMPO will also validate the LEKID technology in a representative space environment. The corrected focal plane is filled with diffraction limited horn-coupled KID arrays, with 19, 37, 23, 41 active pixels respectively at 150, 250, 350, and 460$\:$GHz. Here we report on the full electrical and optical characterization performed on these detector arrays before the flight. In a dark laboratory cryostat, we measured the resonator electrical parameters, such as the quality factors and the electrical responsivities, at a base temperature of 300$\:$mK. The measured average resonator $Q$s are 1.7$\times{10^4}$, 7.0$\times{10^4}$, 1.0$\times{10^4}$, and 1.0$\times{10^4}$ for the 150, 250, 350, and 460$\:$GHz arrays, respectively. The average electrical phase responsivities on resonance are 1.4$\:$rad/pW, 1.5$\:$rad/pW, 2.1$\:$rad/pW, and 2.1$\:$rad/pW; the electrical noise equivalent powers are 45$\:\rm{aW/\sqrt{Hz}}$, 160$\:\rm{aW/\sqrt{Hz}}$, 80$\:\rm{aW/\sqrt{Hz}}$, and 140$\:\rm{aW/\sqrt{Hz}}$, at 12 Hz. In the OLIMPO cryostat, we measured the optical properties, such as the noise equivalent temperatures (NET) and the spectral responses. The measured NET$_{\rm RJ}$s are $200\:\mu\rm{K\sqrt{s}}$, $240\:\mu\rm{K\sqrt{s}}$, $240\:\mu\rm{K\sqrt{s}}$, and $\:340\mu\rm{K\sqrt{s}}$, at 12 Hz; under 78, 88, 92, and 90 mK Rayleigh-Jeans blackbody load changes respectively for the 150, 250, 350, and 460 GHz arrays. The spectral responses were characterized with the OLIMPO differential Fourier transform spectrometer (DFTS) up to THz frequencies, with a resolution of 1.8 GHz.Comment: Published on JCA

Buffering Adaptive Immunity by Hydrogen Sulfide

Abstract: T cell-mediated adaptive immunity is designed to respond to non-self antigens and pathogens through the activation and proliferation of various T cell populations. T helper 1 (Th1), Th2, Th17 and Treg cells finely orchestrate cellular responses through a plethora of paracrine and autocrine stimuli that include cytokines, autacoids, and hormones. Hydrogen sulfide (H2S) is one of these mediators able to induce/inhibit immunological responses, playing a role in inflammatory and autoimmune diseases, neurological disorders, asthma, acute pancreatitis, and sepsis. Both endogenous and exogenous H2S modulate numerous important cell signaling pathways. In monocytes, polymorphonuclear, and T cells H2S impacts on activation, survival, proliferation, polarization, adhesion pathways, and modulates cytokine production and sensitivity to chemokines. Here, we offer a comprehensive review on the role of H2S as a natural buffer able to maintain over time a functional balance between Th1, Th2, Th17 and Treg immunological responses

Real-life appraisal on blood pressure targets achievement in adult outpatients at high cardiovascular risk

Background and aim: Although hypertension guidelines highlight the benefits of achieving the recommended blood pressure (BP) targets, hypertension control rate is still insufficient, mostly in high or very high cardiovascular (CV) risk patients. Thus, we aimed to estimate BP control in a cohort of patients at high CV risk in both primary and secondary prevention. Methods and results: A single-center, cross-sectional study was conducted by extracting data from a medical database of adult outpatients aged 40–75 years, who were referred to our Hypertension Unit, Rome (IT), for hypertension assessment. Office BP treatment targets were defined according to 2018 ESC/ESH guidelines as: a)&lt;130/80 mmHg in individuals aged 40–65 years; b)&lt;140/80 mmHg in subjects aged &gt;65 years. Primary prevention patients with SCORE &lt;5% were considered to be at low-intermediate risk, whilst individuals with SCORE ≥5% or patients with comorbidities were defined to be at very high risk. Among 6354 patients (47.2% female, age 58.4 ± 9.6 years), 4164 (65.5%) were in primary prevention with low-intermediate CV risk, 1831 (28.8%) in primary prevention with high-very high CV risk and 359 (5.6%) in secondary prevention. In treated hypertensive outpatients, uncontrolled hypertension rate was significantly higher in high risk primary prevention than in low risk primary prevention and secondary prevention patients (18.4% vs 24.4% vs. 12.5%, respectively; P &lt; 0.001). In high risk primary prevention diabetic patients only 10% achieved the recommended BP targets. Conclusions: Our data confirmed unsatisfactory BP control among high-risk patients, both in primary and secondary prevention, and suggest the need for a more stringent BP control policies in these patients

Nanoliter contact angle probes tumor angiogenic ligand-receptor protein interactions

Any molecular recognition reaction supported by a solid-phase drives a specific change of the solid-solution interfacial tension. Sessile Contact Angle (CA) experiments can be readily used to track this thermodynamic parameter, prompting this well-known technique to be reinvented as an alternative, easy-access and label-free way to probe and study molecular recognition events. Here we deploy this technique, renamed for this application CONAMORE (CONtact Angle MOlecular REcognition), to study the interaction of the tumor-derived pro-angiogenic vascular endothelial growth factor-A (VEGF-A) with the extracellular domain of its receptor VEGFR2. We show that CONAMORE recognizes the high affinity binding of VEGF-A at nanomolar concentrations to surface-immobilized VEGFR2 regardless of the presence of a ten folds excess of a non specific interacting protein, and that it further proofs its specificity and reliability on competitive binding experiments involving neutralizing anti-VEGF-A antibodies. Finally, CONAMORE shows the outstanding capability to detect the specific interaction between VEGFR2 and low molecular weight ligands, such as Cyclo-VEGI, a VEGFR2 antagonist cyclo-peptide, that weights about 2 kDa

TR-644 a novel potent tubulin binding agent induces impairment of endothelial cells function and inhibits angiogenesis.

TR-644 is a novel combretastatin A-4 (CA-4) analogue endowed with potent microtubule depolymerizing activity superior to that of the lead compound and it also has high affinity to colchicines binding site of tubulin. We tested TR-644 anti-angiogenic effects in human umbilical endothelial cells (HUVEC). It showed no significant effects on the growth of HUVEC cells at concentrations below 1,000 nM, but at much lower concentrations (10-100 nM) it induced inhibition of capillary tube formation, inhibition of endothelial cell migration and affected endothelial cell morphology as demonstrated by the disruption of the microtubule network. TR-644 also increased permeability of HUVEC cells in a time dependent manner. The molecular mechanism for the anti-vascular activity of TR-644 was investigated in detail. TR-644 caused G2/M arrest in endothelial cells and this effect correlated with downregulation of the expression of Cdc25C and Cdc2Tyr15. Moreover TR-644 inhibited VEGF-induced phosphorylation of VE-cadherin but did not prevent the VEGF-induced phosphorylation of FAK. In chick chorioallantoic membrane in vivo assay, TR-644 (0.1-1.0 pmol/egg) efficiently counteracted the strong angiogenic response induced by FGF. Also CA-4, used as reference compound, caused an antagonistic effect, but in contrast, it induced per se, a remarkable angiogenic response probably due to an inflammatory reaction in the site of treatment. In a mice allogenic tumor model, immunohistochemical staining of tumors with anti-CD31 antibody showed that TR-644 significantly reduced the number of vessel, after 24 h from the administration of a single dose (30 mg/Kg)