Differential automatic zero-adjusting amplifier

A method is described for building a low-voltage-drift differential dc amplifier featuring automatic zero adjustment, a high input impedance, and a bandwidth of 10 kHz. This is achieved by an asymmetric two-step process between the input signal and ground. Bandwidth can be extended by the use of a second amplifier during the ground-sampling time. The amplifier can be made with standard electronic components. A major advantage of this method is that an existing amplifier can easily be converted into a low-voltage-drift amplifier by adding the essential elements of the described automatic zero-adjusting amplifier to its input stage. To illustrate the method a practical example is constructed featuring a drift of 0.2 microV/ degrees C.     

单颗粒大气气溶胶的同步辐射微束X射线研究

在北京同步辐射装置4W1B光束线的荧光站,用束斑大小为20 μm×10 μm的X射线微束分析了污染排放源PM10单颗粒和环境空气监测样品PM10单颗粒,得到了单颗粒的X射线荧光谱。实验结果表明,来自不同污染排放源的颗粒物,它们的能谱具有明显的特征,根据颗粒物的能谱可以识别颗粒物的来源。     

ANSIM: an anesthesia simulator for the IBM PC

Simulations based on physiologic modeling have been used for over twenty years to clarify the pharmacokinetics of inhaled anesthetics. We describe ANSIM, an anesthesia simulator for the IBM PC. ANSIM uses established modeling techniques to create a life-like anesthesia simulator. ANSIM is useful as an educational tool for demonstrating classic concepts of uptake and distribution of inhaled anesthetics.     

Genetic Dissection of Light-Regulated Adventitious Root Induction in Arabidopsis thaliana Hypocotyls

Photomorphogenic responses of etiolated seedlings include the inhibition of hypocotyl elongation and opening of the apical hook. In addition, dark-grown seedlings respond to light by the formation of adventitious roots (AR) on the hypocotyl. How light signaling controls adventitious rooting is less well understood. Hereto, we analyzed adventitious rooting under different light conditions in wild type and photomorphogenesis mutants in Arabidopsis thaliana. Etiolation was not essential for AR formation but raised the competence to form AR under white and blue light. The blue light receptors CRY1 and PHOT1/PHOT2 are key elements contributing to the induction of AR formation in response to light. Furthermore, etiolation-controlled competence for AR formation depended on the COP9 signalosome, E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC (COP1), the COP1 interacting SUPPRESSOR OF PHYA-105 (SPA) kinase family members (SPA1,2 and 3) and Phytochrome-Interacting Factors (PIF). In contrast, ELONGATED HYPOCOTYL5 (HY5), suppressed AR formation. These findings provide a genetic framework that explains the high and low AR competence of Arabidopsis thaliana hypocotyls that were treated with dark, and light, respectively. We propose that light-induced auxin signal dissipation generates a transient auxin maximum that explains AR induction by a dark to light switch.     

Circulating Monocyte Subsets and Transcatheter Aortic Valve Replacement

Transcatheter aortic valve replacement (TAVR), as an alternative to open heart surgery, has revolutionized the treatment of severe aortic valve stenosis (AVS), the most common valvular disorder in the elderly. AVS is now considered a form of atherosclerosis and, like the latter, partly of inflammatory origin. Patients with high-grade AVS have a highly disturbed blood flow associated with high levels of shear stress. The immediate reopening of the valve during TAVR leads to a sudden restoration of a normal blood flow hemodynamic. Despite its good prognosis for patients, TAVR remains associated with bleeding or thrombotic postprocedural complications, involving mechanisms that are still poorly understood. Many studies report the close link between blood coagulation and inflammation, termed thromboinflammation, including monocytes as a major actor. The TAVR procedure represents a unique opportunity to study the influence of shear stress on human monocytes, key mediators of inflammation and hemostasis processes. The purpose of this study was to conduct a review of the literature to provide a comprehensive overview of the impact of TAVR on monocyte phenotype and subset repartition and the association of these parameters with the clinical outcomes of patients with severe AVS who underwent TAVR.     

Could SGLT2 Inhibitors Improve Exercise Intolerance in Chronic Heart Failure?

Despite the constant improvement of therapeutical options, heart failure (HF) remains associated with high mortality and morbidity. While new developments in guideline-recommended therapies can prolong survival and postpone HF hospitalizations, impaired exercise capacity remains one of the most debilitating symptoms of HF. Exercise intolerance in HF is multifactorial in origin, as the underlying cardiovascular pathology and reactive changes in skeletal muscle composition and metabolism both contribute. Recently, sodium-related glucose transporter 2 (SGLT2) inhibitors were found to improve cardiovascular outcomes significantly. Whilst much effort has been devoted to untangling the mechanisms responsible for these cardiovascular benefits of SGLT2 inhibitors, little is known about the effect of SGLT2 inhibitors on exercise performance in HF. This review provides an overview of the pathophysiological mechanisms that are responsible for exercise intolerance in HF, elaborates on the potential SGLT2-inhibitor-mediated effects on these phenomena, and provides an up-to-date overview of existing studies on the effect of SGLT2 inhibitors on clinical outcome parameters that are relevant to the assessment of exercise capacity. Finally, current gaps in the evidence and potential future perspectives on the effects of SGLT2 inhibitors on exercise intolerance in chronic HF are discussed.     

Preclinical Assessment of the Combination of PSMA-Targeting Radionuclide Therapy with PARP Inhibitors for Prostate Cancer Treatment

Prostate specific membrane antigen targeted radionuclide therapy (PSMA-TRT) is a promising novel treatment for prostate cancer (PCa) patients. However, PSMA-TRT cannot be used for curative intent yet, thus additional research on how to improve the therapeutic efficacy is warranted. A potential way of achieving this, is combining TRT with poly ADP-ribosylation inhibitors (PARPi), which has shown promising results for TRT of neuroendocrine tumor cells. Currently, several clinical trials have been initiated for this combination for PCa, however so far, no evidence of synergism is available for PCa. Therefore, we evaluated the combination of PSMA-TRT with three classes of PARPi in preclinical PCa models. In vitro viability and survival assays were performed using PSMA-expressing PCa cell lines PC3-PIP and LNCaP to assess the effect of increasing concentrations of PARPi veliparib, olaparib or talazoparib in combination with PSMA-TRT compared to single PARPi treatment. Next, DNA damage analyses were performed by quantifying the number of DNA breaks by immunofluorescent stainings. Lastly, the potential of the combination treatments was studied in vivo in mice bearing PC3-PIP xenografts. Our results show that combining PSMA-TRT with PARPi did not synergistically affect the in vitro clonogenic survival or cell viability. DNA-damage analysis revealed only a significant increase in DNA breaks when combining PSMA-TRT with veliparib and not in the other combination treatments. Moreover, PSMA-TRT with PARPi treatment did not improve tumor control compared to PSMA-TRT monotherapy. Overall, the data presented do not support the assumption that combining PSMA-TRT with PARPi leads to a synergistic antitumor effect in PCa. These results underline that extensive preclinical research using various PCa models is imperative to validate the applicability of the combination strategy for PCa, as it is for other cancer types.     

Nonparallel training for voice conversion based on a parameter adaptation approach

The objective of voice conversion algorithms is to modify the speech by a particular source speaker so that it sounds as if spoken by a different target speaker. Current conversion algorithms employ a training procedure, during which the same utterances spoken by both the source and target speakers are needed for deriving the desired conversion parameters. Such a (parallel) corpus, is often difficult or impossible to collect. Here, we propose an algorithm that relaxes this constraint, i.e., the training corpus does not necessarily contain the same utterances from both speakers. The proposed algorithm is based on speaker adaptation techniques, adapting the conversion parameters derived for a particular pair of speakers to a different pair, for which only a nonparallel corpus is available. We show that adaptation reduces the error obtained when simply applying the conversion parameters of one pair of speakers to another by a factor that can reach 30%. A speaker identification measure is also employed that more insightfully portrays the importance of adaptation, while listening tests confirm the success of our method. Both the objective and subjective tests employed, demonstrate that the proposed algorithm achieves comparable results with the ideal case when a parallel corpus is available.     

Synthesis of atom probe experiments on irradiation-induced solute segregation in French ferritic pressure vessel steels

Microstructural changes due to neutron irradiation cause an evolution of the mechanical properties of reactor pressure vessels (RPV) steels. This paper aims at identifying and characterising the microstructural changes which have been found to be responsible in part for the observed embrittlement. This intensive work relies principally on an atom probe (AP) study of a low Cu-level French RPV steel (Chooz A). This material has been irradiated in in-service conditions for 0–16 years in the frame of the surveillance program. Under this aging condition, solute clustering occurs (Cu, Ni, Mn, Si, P, …). In order to identify the role of copper, experiments were also carried out on Fe–Cu model alloys submitted to different types of irradiations (neutron, electron, ion). Cu-cluster nucleation appears to be directly related to the presence of displacement cascades during neutron (ion) irradiation. The operating basic physical process is not clearly identified yet. A recovery of the mechanical properties of the irradiated material can be achieved by annealing treatments (20 h at 450°C in the case of the RPV steel under study, following microhardness measurements). It has been shown that the corresponding microstructural evolution was a rapid dissolution of the high number density of irradiation-induced solute clusters and the precipitation of a very low number density of Cu-rich particles.