11 research outputs found
Shadow monochromatic backlighting: Large-field high resolution X-ray shadowgraphy with improved spectral tunability
The shadow monochromatic backlighting (SMB) scheme, a modification
of the well-known soft X-ray monochromatic backlighting scheme,
is proposed. It is based on a spherical crystal as the dispersive
element and extends the traditional scheme by allowing one to
work with a wide range of Bragg angles and thus in a wide spectral
range. The advantages of the new scheme are demonstrated
experimentally and supported numerically by ray-tracing
simulations. In the experiments, the X-ray backlighter source
is a laser-produced plasma, created by the interaction of an
ultrashort pulse, Ti:Sapphire laser (120 fs, 3–5 mJ,
1016 W/cm2 on target) or a short wavelength
XeCl laser (10 ns, 1–2 J, 1013 W/cm2 on
target) with various solid targets (Dy, Ni + Cr, BaF2).
In both experiments, the X-ray sources are well localized spatially
(∼20 μm) and are spectrally tunable in a relatively wide
wavelength range (λ = 8–15 Å). High quality monochromatic
(δλ/λ ∼ 10−5–10−3)
images with high spatial resolution (up to ∼4 μm) over a large field
of view (a few square millimeters) were obtained. Utilization
of spherically bent crystals to obtain high-resolution, large
field, monochromatic images in a wide range of Bragg angles
(35° < Θ < 90°) is demonstrated for the first
time
MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients
Patients with primary HER2-positive breast cancer benefit from HER2-targeted therapies. Nevertheless, a significant proportion of these patients die of disease progression due to mechanisms of drug resistance. MicroRNAs (miRNAs) are emerging as critical core regulators of drug resistance that act by modulating the epithelial- to-mesenchymal transition (EMT) and cancer-related immune responses. In this study, we investigated the association between the expression of a specific subset of 14 miRNAs involved in EMT processes and immune functions and the response to neoadjuvant trastuzumab and chemotherapy in 52 patients with HER2-overexpressing breast tumors. The expression of only a single miRNA, miR-21, was significantly associated with residual disease (p = 0.030) and increased after trastuzumab-chemotherapy (p = 0.012). A target prediction analysis coupled with in vitro and in vivo validations revealed that miR-21 levels inversely correlated with the expression of PTEN (rs = −0.502; p = 0.005) and PDCD4 (rs = −0.426; p = 0.019), which differentially influenced the drug sensitivity of HER2-positive breast cancer cells. However, PTEN expression was only marginally associated with residual disease. We further demonstrated that miR-21 was able to affect the response to both trastuzumab and chemotherapy, triggering an IL-6/STAT3/NF-κB-mediated signaling loop and activating the PI3K pathway. Our findings support the ability of miR-21 signaling to sustain EMT and shape the tumor immune microenvironment in HER2-positive breast cancer. Collectively, these data provide a rationale for using miR-21 expression as a biomarker to select trastuzumab-chemotherapy-resistant HER2-positive breast cancer patients who may benefit from treatments containing PI3K inhibitors or immunomodulatory drugs
X-ray radiation from ions with K-shell vacancies
Abstract New types of space resolved X-ray spectra produced in light matter experiments with high intensity lasers have been investigated experimentally and theoretically. This type of spectra is characterised by the disappearance of distinct resonance line emission and the appearance of very broad emission structures due to the dielectronic satellite transitions associated to the resonance lines. Atomic data calculations have shown, that rather exotic states with K-shell vacancies are involved. For quantitative spectra interpretation we developed a model for dielectronic satellite accumulation (DSA-model) in cold dense optically thick plasmas which are tested by rigorous comparison with space resolved spectra from ns-lasers. In experiments with laser intensities up to 10 19 W/cm 2 focused into nitrogen gas targets, hollow ion configurations are observed by means of soft X-ray spectroscopy. It is shown that transitions in hollow ions can be used for plasma diagnostic. The determination of the electron temperature in the long lasting recombining regime is demonstrated. In Light-matter interaction experiments with extremely high contrast (up to 10 10 ) short pulse (400 fs) lasers electron densities of n e ≈3×10 23 cm −3 at temperatures between kT e =200–300 eV have been determined by means of spectral simulations developed previously for ns-laser produced plasmas. Expansion velocities are determined analysing asymmetric optically thick line emission. Further, the results are checked by observing the spectral windows involving the region about the He α -line and the region from the He β -line to the He-like continuum. Finally, plasmas of solid density are characteristic in experiments with heavy ion beams heating massive targets. We report the first spectroscopic investigations in plasmas of this type with results on solid neon heated by Ar-ions. A spectroscopic method for the determination of the electron temperature in extreme optically thick plasmas is developed
Workers' motor efficiency assessment through an IMU-based standardized test and an automated and error-minimizing measurement procedure
Irrigation channels-groundwater interaction: a meta-modeling framework to support water saving in agriculture
Objective Evaluation of Coordinative Abilities and Training Effectiveness in Sports Scenarios: An Automated Measurement Protocol
The monitoring of coordinative abilities in sports applications is often carried out by trainers that adopt subjective protocols and evaluations not supported by repeatable and reproducible measurement setups. This often leads to unreliable evaluations that do not allow us to quantify the positive or negative effect of some training in a simple way. In this scenario, the rapid spreading of wearable devices able to capture human movements providing data to the users could be a useful instrument to face the problem of simplifying the development of automated, repeatable, and reproducible measurement procedures easily adoptable by a community of athletes or coaches. Following this path, the paper proposes an automatic measurement protocol for the assessment of coordinative abilities based on the use of IMUs embedded in wearable devices. A new protocol based on the ruler and tapping tests and a set of objective key performance indicators, derived from IMU measurements, to evaluate the outcome of the test is then developed. In detail, the protocol is based on the sequence 1) ruler test; 2) tapping test; 3) ruler test. The tapping test is performed until energy exhaustion to try and identify, from inertial data, features that can describe possible fatigue effects and correlations with reaction time. Ruler tests are adopted to evaluate the reaction time. The first ruler test provides reaction time information in rest conditions, while the last one considers it after a repeated movement. The comparison of these two times will show whether the reaction time changes after a fatigue condition. An algorithm capable of calculating the number of tapping and the reaction time of each subject is implemented to evaluate the accelerometric data acquired during the tests. Therefore, the impact of the work is two-fold: from an engineering point of view, the automation and performance evaluation of the proposed algorithm is provided; from a sport-medical perspective, the main finding is a general reduction of the reaction time after the energy-exhausting tapping test, as if this last could be considered as a powerful warm-up exercise for sports people. Two are the main results achieved: i) the proposed protocol allows a reduction of the reactions time in about the 83% of cases; ii) the proposed measurement system allows obtaining, regarding the tapping test, additional very useful quantities as the tap intertemps, frequency spectra, and acceleration excursions, which typically are not provided in state-of-the-art tapping test execution
An immune stratification reveals a subset of PD-1/LAG-3 double-positive triple-negative breast cancers.
Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients
Patients with primary HER2-positive breast cancer benefit from HER2-targeted therapies. Nevertheless, a significant proportion of these patients die of disease progression due to mechanisms of drug resistance. MicroRNAs (miRNAs) are emerging as critical core regulators of drug resistance that act by modulating the epithelial- to-mesenchymal transition (EMT) and cancer-related immune responses. In this study, we investigated the association between the expression of a specific subset of 14 miRNAs involved in EMT processes and immune functions and the response to neoadjuvant trastuzumab and chemotherapy in 52 patients with HER2-overexpressing breast tumors. The expression of only a single miRNA, miR-21, was significantly associated with residual disease (p = 0.030) and increased after trastuzumab-chemotherapy (p = 0.012). A target prediction analysis coupled with in vitro and in vivo validations revealed that miR-21 levels inversely correlated with the expression of PTEN (rs = −0.502; p = 0.005) and PDCD4 (rs = −0.426; p = 0.019), which differentially influenced the drug sensitivity of HER2-positive breast cancer cells. However, PTEN expression was only marginally associated with residual disease. We further demonstrated that miR-21 was able to affect the response to both trastuzumab and chemotherapy, triggering an IL-6/STAT3/NF-κB-mediated signaling loop and activating the PI3K pathway. Our findings support the ability of miR-21 signaling to sustain EMT and shape the tumor immune microenvironment in HER2-positive breast cancer. Collectively, these data provide a rationale for using miR-21 expression as a biomarker to select trastuzumab-chemotherapy-resistant HER2-positive breast cancer patients who may benefit from treatments containing PI3K inhibitors or immunomodulatory drugs
Additional file 2: Figure S1. of An immune stratification reveals a subset of PD-1/LAG-3 double-positive triple-negative breast cancers
Prognostic value of the binary tumor-infiltrating lymphocytes (TILs) cutoff ≥ 20% in triple-negative breast cancer (TNBC) patients of the discovery cohort stratified by nodal status. Figure S2. Correlation between the expression of PD-1 and LAG-3 and the presence of CD8+ cells in triple-negative breast cancer (TNBC). (PDF 397 kb