Diamond-based sensors for in vitro cellular radiobiology: Simultaneous detection of cell exocytic activity and ionizing radiation

The investigation of secondary effects induced by ionizing radiation represents a new and ever-growing research field in radiobiology. This new paradigm cannot be investigated only using standard instrumentation and methodologies, but rather requires novel technologies to achieve significant progress. In this framework, we developed diamond-based sensors that allow simultaneous real-time measurements with a high spatial resolution of the secretory activity of a network of cells cultured on the device, as well as of the dose at which they are exposed during irradiation experiments. The devices were functionally characterized by testing both the above-mentioned detection schemes, namely: amperometric measurements of neurotransmitter release from excitable cells (such as dopamine or adrenaline) and dosimetric evaluation using different ionizing particles (alpha particle and X-ray photons). Finally, the sensors were employed to investigate the effects induced by X-rays on the exocytotic activity of PC12 neuroendocrine cells by monitoring the modulation of the dopamine release in real-time

Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach

Autosomal dominant polycystic disease (ADPKD) is the most frequent monogenic kidney disease. It causes progressive renal failure, endothelial dysfunction, and hypertension, all of which are strictly linked to oxidative stress (OxSt). Treatment with tolvaptan is known to slow the renal deterioration rate, but not all the molecular mechanisms involved in this effect are well-established. We evaluated the OxSt state in untreated ADPKD patients compared to that in tolvaptan-treated ADPKD patients and healthy subjects. OxSt was assessed in nine patients for each group in terms of mononuclear cell p22phox protein expression, NADPH oxidase key subunit, MYPT-1 phosphorylation state, marker of Rho kinase activity (Western blot) and heme oxygenase (HO)-1, induced and protective against OxSt (ELISA). p22phox protein expression was higher in untreated ADPKD patients compared to treated patients and controls: 1.42 ± 0.11 vs. 0.86 ± 0.15 d.u., p = 0.015, vs. 0.53 ± 0.11 d.u., p < 0.001, respectively. The same was observed for phosphorylated MYPT-1: 0.96 ± 0.28 vs. 0.68 ± 0.09 d.u., p = 0.013 and vs. 0.47 ± 0.13 d.u., p < 0.001, respectively, while the HO-1 expression of untreated patients was significantly lower compared to that of treated patients and controls: 5.33 ± 3.34 vs. 2.08 ± 0.79 ng/mL, p = 0.012, vs. 1.97 ± 1.22 ng/mL, p = 0.012, respectively. Tolvaptan-treated ADPKD patients have reduced OxSt levels compared to untreated patients. This effect may contribute to the slowing of renal function loss observed with tolvaptan treatment

ESD experiments and simulations on RF CMOS switches

Modernste Bulk-Silizium-HF-Antennenschalter werden aus Multi-Finger N-Kanal-MOSFET-Transistoren in gestapelter Konguration aufgebaut, d.h. die Transistorblöcke sind in Reihe geschaltet. Aufgrund der kritischen Position dieser Schalter im HF-Antennen-Frontend werden Selbstschutzschaltungen gegen elektrostatische Entladungen (ESD) eingesetzt um die HF-Leistung nicht zu reduzieren. Diese Tatsache impliziert, dass die gestapelten Transistoren in einem großen Operationsbereich untersucht werden müssen, um mögliche Ursachen von Schwachstellen wie hohem Leckstrom und niedrige ESD-Robustheit zu erkennen. In dieser Arbeit wird das ESD-Verhalten von gestapelten Multi-Finger-Transistoren für HF-Antennenschalteranwendungen in 0.13um Bulk-Silizium-Technologie mittels einer Kombination aus Experimenten und Simulationen untersucht. Für diese Untersuchungen werden mehrere Messtechniken eingesetzt, wie die Transmission Line Pulse (TLP)-Technik, das transiente interferometrische Mapping (TIM) und die Emissionsmikroskopie (EMMI). Aufgrund der Komplexität der gestapelten Bauelemente werden SPICE-Simulationen verwendet, um ein tieferes Verständnis der transienten Entwicklung aller Transistoren zu erhalten welche zur gestapelten Konguration von CMOS-Blöcken gehören. Die Ursachen für schwache Leistungsfähigkeit werden sowohl an Einzeltransistoren als auch an der gestapelten Konguration untersucht. Spezielle Messungen werden zur Erstellung präziser Modelle präsentiert, die einen großen Arbeitsbereich unter ESD Bedingungen abdecken können und die zur Kalibration von TIM-Messungen dienen. Darauf basierend präsentieren wir Ihnen einzigartige TLP-Wellenformen und den Leistungsverbrauch von gestapelten Transistoren, und leiten den Einuss und die Interaktion zwischen CMOS Blöcken über deren Substrat her.State-of-the-art bulk silicon RF antenna switches are built by multi-nger nMOSFET transistors connected in stacked conguration, i.e. the transistor blocks are connected in series. Due to the critical location in the RF antenna front-end, an electrostatic-discharge (ESD) self-protection approach is the normal choice to not degrade the RF performance. This fact implies that the stacked devices must be studied in a broad bias operations to detect possible causes of weaknesses, high leakage and low ESD robustness. In this thesis work, the ESD behavior of stacked multi-nger transistors for RF an-tenna switch applications for 0.13 m bulk silicon technology is analyzed by means of a combinations of experiments and simulations. Several measurements technique are exploited for the investigation, like transmission line pulse (TLP) technique, transient interferometric mapping (TIM) technique and emission microscopy (EMMI) technique. Moreover, due to the complexity of the stacked devices, SPICE simulations are used to have deeper understanding of the transient evolution of all transistors belonging to the stacked conguration of CMOS blocks. The reasons of weak product device performances are investigated on both single transistor device and stacked transistor test structures. Dedicated measurements are presented for creation of accurate models able to cover a wide operation range under ESD conditions and for calibration of TIM measurements. Thanks to all of this, we explain unique TLP waveforms and power dissipation on stacked devices discovering the impact of the interaction of the CMOS blocks via substrate.14

Autologous Cell Therapy for Peripheral Arterial Disease: Systematic Review and Meta-Analysis of Randomized, Nonrandomized, and Noncontrolled Studies

none3nomixedRigato, Mauro; Monami, Matteo; Fadini, Gian PaoloRigato, Mauro; Monami, Matteo; Fadini, GIAN PAOL

Genotype-phenotype correlation in Gordon's syndrome: report of two cases carrying novel heterozygous mutations

Gordon's syndrome, known also as Pseudohypoaldosteronism type II is a rare inherited dominant form of low-renin hypertension associated with hyperkalemia and metabolic acidosis. Four genes related to the regulation of the NaCl co-symporter NCC have been discovered associated to Gordon phenotypes: WINK 1 and WINK4, which, along with WNK2 and WNK3, encode a family of WNK-kinases, and KLHL3 and CUL3 encoding respectively, Kelch-like 3 protein and cullin. Heterozygous mutations in these genes constitutively activate NCC leading to abnormally increased salt reabsorption and salt-sensitive hypertension. Thiazide diuretic is the recognized treatment for this condition. We report and discuss phenotypic and genetic heterogeneity of two patients with Gordon's syndrome carrying novel heterozygous mutations in the WNK1 and KLHL3 genes. A very rare variant in the SCNN1G gene encoding the gamma subunit of epithelial sodium channel ENaC was also identified in one patient

Clinical Evidence for the Choice of the Direct Oral Anticoagulant in Patients with Atrial Fibrillation According to Creatinine Clearance

Atrial fibrillation (AF) often coexists with chronic kidney disease (CKD), which confer to the patient a higher risk of both thromboembolic and hemorrhagic events. Oral anticoagulation therapy, nowadays preferably with direct oral anticoagulants (DOACs), represents the cornerstone for ischemic stroke prevention in high-risk patients. However, all four available DOACs (dabigatran, apixaban, rivaroxaban and edoxaban) are eliminated by the kidneys to some extent. Reduced kidney function facilitates DOACs accumulation and, therefore, different dose reductions are required, with slight differences between American and European recommendations especially in case of severe renal impairment (creatinine clearance < 30 mL/min). Overall, the use of DOACs in patients with non-end stage CKD and AF is effective similarly to warfarin, showing a better safety profile. The management of thromboembolic risk among patients with AF on dialysis remains challenging, as warfarin effectiveness for stroke prevention in this population is questionable and retrospective data on apixaban need to be confirmed on a larger scale. In kidney transplant recipients, DOACs may provide a potentially safer option compared to warfarin, but co-administration with immunosuppressants is a matter of concern