Detection of low energy single ion impacts in micron scale transistors at room temperature

We report the detection of single ion impacts through monitoring of changes in the source-drain currents of field effect transistors (FET) at room temperature. Implant apertures are formed in the interlayer dielectrics and gate electrodes of planar, micro-scale FETs by electron beam assisted etching. FET currents increase due to the generation of positively charged defects in gate oxides when ions (121Sb12+, 14+, Xe6+; 50 to 70 keV) impinge into channel regions. Implant damage is repaired by rapid thermal annealing, enabling iterative cycles of device doping and electrical characterization for development of single atom devices and studies of dopant fluctuation effects

Atomic layer etching of SiO2 with Ar and CHF 3 plasmas: A self-limiting process for aspect ratio independent etching

With ever increasing demands on device patterning to achieve smaller critical dimensions, the need for precise, controllable atomic layer etching (ALE) is steadily increasing. In this work, a cyclical fluorocarbon/argon plasma is successfully used for patterning silicon oxide by ALE in a conventional inductively coupled plasma tool. The impact of plasma parameters and substrate electrode temperature on the etch performance is established. We achieve the self-limiting behavior of the etch process by modulating the substrate temperature. We find that at an electrode temperature of −10°C, etching stops after complete removal of the modified surface layer as the residual fluorine from the reactor chamber is minimized. Lastly, we demonstrate the ability to achieve independent etching, which establishes the potential of the developed cyclic ALE process for small scale device patterning

Effects on health-related quality of life of interventions affecting survival in critically ill patients: a systematic review

Survival has been considered the cornerstone for clinical outcome evaluation in critically ill patients admitted to intensive care unit (ICU). There is evidence that ICU survivors commonly show impairments in long-term outcomes such as quality of life (QoL) considering them as the most relevant ones. In the last years, the concept of patient-important outcomes has been introduced and increasingly reported in peer-reviewed publications. In the present systematic review, we evaluated how many randomized controlled trials (RCTs) were conducted on critically ill patients and reporting a benefit on survival reported also data on QoL. All RCTs investigating nonsurgical interventions that significantly reduced mortality in critically ill patients were searched on MEDLINE/PubMed, Scopus and Embase from inception until August 2021. In a second stage, for all the included studies, the outcome QoL was investigated. The primary outcome was to evaluate how many RCTs analyzing interventions reducing mortality reported also data on QoL. The secondary endpoint was to investigate if QoL resulted improved, worsened or not modified. Data on QoL were reported as evaluated outcome in 7 of the 239 studies (2.9%). The tools to evaluate QoL and QoL time points were heterogeneous. Four interventions showed a significant impact on QoL: Two interventions improved survival and QoL (pravastatin in subarachnoid hemorrhage, dexmedetomidine in elderly patients after noncardiac surgery), while two interventions reduced mortality but negatively influenced QoL (caloric restriction in patients with refeeding syndrome and systematic ICU admission in elderly patients). In conclusion, only a minority of RCTs in which an intervention demonstrated to affect mortality in critically ill patients reported also data on QoL. Future research in critical care should include patient-important outcomes like QoL besides mortality. Data on this topic should be collected in conformity with PROs statement and core outcome sets to guarantee quality and comparability of results

miRNAs in serum exosomes for differential diagnosis of brain metastases

Circulating miRNAs are increasingly studied and proposed as tumor markers with the aim of investigating their role in monitoring the response to therapy as well as the natural evolution of primary or secondary brain tumors. This study aimed to evaluate the modulation of the expression of three miRNAs, miR-21, miR-222 and miR-124-3p, in the serum exosomes of patients with high-grade gliomas (HGGs) and brain metastases (BMs) to verify their usefulness in the differential diagnosis of brain masses; then, it focused on their variations following the surgical and/or radiosurgical treatment of the BMs. A total of 105 patients with BMs from primary lung or breast cancer, or melanoma underwent neurosurgery or radiosurgery treatment, and 91 patients with HGGs were enrolled, along with 30 healthy controls. A significant increase in miR-21 expression in serum exosomes was observed in both HGGs and BMs compared with healthy controls; on the other hand, miR-124-3p was significantly decreased in BMs, and it was increased in HGGs. After the surgical or radiosurgical treatment of patients with BMs, a significant reduction in miR-21 was noted with both types of treatments. This study identified a signature of exosomal miRNAs that could be useful as a noninvasive complementary analysis both in the differential diagnosis of BMs from glial tumors and in providing information on tumor evolution over time

Stress corrosion cracking of additively manufactured alloy 625

Laser bed powder fusion (LPBF) is an additive manufacturing technology for the fabrication of semi-finished components directly from computer-aided design modelling, through melting and consolidation, layer upon layer, of a metallic powder, with a laser source. This manufacturing technique is particularly indicated for poor machinable alloys, such as Alloy 625. However, the unique microstructure generated could modify the resistance of the alloy to environment assisted cracking. The aim of this work was to analyze the stress corrosion cracking (SCC) and hydrogen embrittlement resistance behavior of Alloy 625 obtained by LPBF, both in as-built condition and after a standard heat treatment (grade 1). U-bend testing performed in boiling magnesium chloride at 155 and 170◦C confirmed the immunity of the alloy to SCC. However, slow strain rate tests in simulated ocean water on cathodically polarized specimens highlighted the possibility of the occurrence of hydrogen embrittlement in a specific range of strain rate and cathodic polarization. The very fine grain size and dislocation density of the thermally untreated specimens appeared to increase the hydrogen diffusion and embrittlement effect on pre-charged specimens that were deformed at the high strain rate. Conversely, heat treatment appeared to mitigate hydrogen embrittlement at high strain rates, however at the slow strain rate all the specimens showed a similar behavior

Docking of molecules identified in bioactive medicinal plants extracts into the p50 NF-kappaB transcription factor: correlation with inhibition of NF-kappaB/DNA interactions and inhibitory effects on IL-8 gene expression

<p>Abstract</p> <p>Background</p> <p>The transcription factor NF-kappaB is a very interesting target molecule for the design on anti-tumor, anti-inflammatory and pro-apoptotic drugs. However, the application of the widely-used molecular docking computational method for the virtual screening of chemical libraries on NF-kappaB is not yet reported in literature. Docking studies on a dataset of 27 molecules from extracts of two different medicinal plants to NF-kappaB-p50 were performed with the purpose of developing a docking protocol fit for the target under study.</p> <p>Results</p> <p>We enhanced the simple docking procedure by means of a sort of combined target- and ligand-based drug design approach. Advantages of this combination strategy, based on a similarity parameter for the identification of weak binding chemical entities, are illustrated in this work with the discovery of a new lead compound for NF-kappaB. Further biochemical analyses based on EMSA were performed and biological effects were tested on the compound exhibiting the best docking score. All experimental analysis were in fairly good agreement with molecular modeling findings.</p> <p>Conclusion</p> <p>The results obtained sustain the concept that the docking performance is predictive of a biochemical activity. In this respect, this paper represents the first example of successfully individuation through molecular docking simulations of a promising lead compound for the inhibition of NF-kappaB-p50 biological activity and modulation of the expression of the NF-kB regulated IL8 gene.</p

Sulfatides trigger increase of cytosolic free calcium and enhanced expression of tumor necrosis factor-alpha and interleukin-8 mRNA in human neutrophils. Evidence for a role of L-selectin as a signaling molecule.

Sulfatides have been established recently as ligands for L-selectin, and we investigated whether they trigger transmembrane signals through ligation of L-selectin. We found that sulfatides trigger the increase of cytosolic free calcium in neutrophils and that this effect was strictly dependent on sulfation of the galactose ring, as non-sulfated galactocerebrosides were not stimulatory. Chymotrypsin and phorbol 12-myristate 13-acetate treatment of neutrophils caused shedding of L-selectin, but not of class I major histocompatibility complex antigens or beta 2 integrins, and blunted the capability of neutrophils to respond to sulfatides with an increase of cytosolic free calcium. Four different anti-L-selectin antibodies (DREG-200, LAM1/3, LAM1/6, and LAM1/10), but not four control antibodies directed against different surface molecules of neutrophils, also triggered an increase of cytosolic free calcium. The anti-L-selectin antibodies were stimulatory both if used in a soluble form, after cross-linking with anti-mouse F(ab')2 fragments, and immobilized to protein A of Staphylococcus aureus through the Fc fragment. With immobilized antibodies, an increase of cytosolic free calcium was found also by plating neutrophils on antibodies bound to protein A-coated coverslips and monitoring the increase of cytosolic free calcium by fluorescence microscopy. Both sulfatides and anti-L-selectin antibody effects were not inhibited by pertussis toxin, thus indicating that a pertussis toxin-sensitive GTP-binding protein was not involved in signal transduction. Sulfatides also triggered an increase of tumor necrosis factor-alpha and interleukin-8 mRNAs in neutrophils. Also to act as stimuli of cytokine mRNA expression, sulfatides required sulfation of the galactose ring, as non-sulfated galactocerebrosides were not stimulatory, and depended on expression of L-selectin, as shedding of this molecules induced by chymotrypsin blunted their effects. These findings suggest that L-selectin can transduce signals activating selective cell function