Gate Electrodes Enable Tunable Nanofluidic Particle Traps

The ability to control the location of nanoscale objects in liquids is essential for fundamental and applied research from nanofluidics to molecular biology. To overcome their random Brownian motion, the electrostatic fluidic trap creates local minima in potential energy by shaping electrostatic interactions with a tailored wall topography. However, this strategy is inherently static -- once fabricated the potential wells cannot be modulated. Here, we propose and experimentally demonstrate that such a trap can be controlled through a buried gate electrode.We measure changes in the average escape times of nanoparticles from the traps to quantify the induced modulations of 0.7k_\rm{B}T in potential energy and 50 mV in surface potential. Finally, we summarize the mechanism in a parameter-free predictive model, including surface chemistry and electrostatic fringing, that reproduces the experimental results. Our findings open a route towards real-time controllable nanoparticle traps

Characterization of the Sos Enattos site for the Einstein Telescope

In this work we report the ongoing characterization of the Sos Enattos former mine (Sardinia, Italy), one of the two candidate sites for the Einstein Telescope (ET), the European third-generation underground interferometric detector of Gravitational Waves. The Sos Enattos site lies on a crystalline basement, made of rocks with good geomechanical properties, characterized by negligible groundwater. In addition, the site has a very low seismic background noise due to the absence of active tectonics involving Sardinia. Finally, the area has a low population density, resulting in a reduced anthropic noise even at the ground level. This location was already studied in 2012-2014 as a promising site for an underground detector. More recently, in March 2019, we deployed a new network of surface and underground seismometers at the site, that is currently monitoring the local seismic noise. Most of the energy carried by the seismic waves is due to the microseisms below 1 Hz, showing a significant correlation with the waves of the west Mediterranean sea. Above 1 Hz the seismic noise in the underground levels of the mine approaches the Peterson's low noise model. Exploiting mine blasting works into the former mine, we were also able to perform active seismic measurements to evaluate the seismic waves propagation across the area. In conclusion we also give a first assessment about the acoustic and magnetic noise in this underground site

Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey

Background: Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety profile, dose intensity, and activity of different chemotherapy regimens in this setting.Patients and methods: gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible. A descriptive analysis of chemotherapy toxicity, dose intensity, response, and survival outcomes was performed.Results: A total of 85 gBRCA1-2pv PDAC patients treated in 21 Italian centers between December 2008 and March 2021 were enrolled. Seventy-four patients were assessable for toxicity and dose intensity, 83 for outcome. Dose intensity was as follows: nab-paclitaxel 72%, gemcitabine 76% (AG); cisplatin 75%, nab-paclitaxel 73%, capecitabine 73%, and gemcitabine 65% (PAXG); fluorouracil 35%, irinotecan 58%, and oxaliplatin 64% (FOLFIRINOX). When compared with the literature, grade 3-4 neutropenia, thrombocytopenia, and diarrhea were increased with PAXG, and unmodified with AG and FOLFIRINOX. RECIST responses were numerically higher with the three-(81%) or four-drug (73%) platinum-containing regimens that outperformed AG (41%) and oxaliplatin-based doublets (56%). Carbohydrate antigen 19.9 (CA19.9) reduction >89% at nadir was reported in two-third of metastatic patients treated with triplets and quadruplets, as opposed to 33% and 45% of patients receiving oxaliplatin-based doublets or AG, respectively. All patients receiving AG experienced disease progression, with a median progression-free survival (mPFS) of 6.4 months, while patients treated with platinum-containing triplets or quadruplets had an mPFS >10.8 months. Albeit still immature, data on overall survival seemed to parallel those on PFS.Conclusions: Our data, as opposed to figures expected from the literature, highlighted that platinum-based regimens provoked an increased toxicity on proliferating cells, when dose intensity was maintained, or an as-expected toxicity, when dose intensity was reduced, while no change in toxicity and dose intensity was evident with AG. Furthermore, an apparently improved outcome of platinum-based triplets or quadruplets over other regimens was observed

Transcription factor Sox10 orchestrates activity of a neural crest-specific enhancer in the vicinity of its gene

The Sox10 transcription factor is a central regulator of vertebrate neural crest and nervous system development. Its expression is likely controlled by multiple enhancer elements, among them U3 (alternatively known as MCS4). Here we analyze U3 activity to obtain deeper insights into Sox10 function and expression in the neural crest and its derivatives. U3 activity strongly depends on the presence of Sox10 that regulates its own expression as commonly observed for important developmental regulators. Sox10 bound directly as monomer to at least three sites in U3, whereas a fourth site preferred dimers. Deletion of these sites efficiently reduced U3 activity in transfected cells and transgenic mice. In stimulating the U3 enhancer, Sox10 synergized with many other transcription factors present in neural crest and developing peripheral nervous system including Pax3, FoxD3, AP2α, Krox20 and Sox2. In case of FoxD3, synergism involved Sox10-dependent recruitment to the U3 enhancer, while Sox10 and AP2α each had to bind to the regulatory region. Our study points to the importance of autoregulatory activity and synergistic interactions for maintenance of Sox10 expression and functional activity of Sox10 in the neural crest regulatory network