Highly Active W2C-Based Composites for the HER in Alkaline Solution: the Role of Surface Oxide Species.

The hydrogen evolution reaction (HER) is a crucial electrochemical process for the proposed hydrogen economy since it has the potential to provide pure hydrogen for fuel cells. Nowadays, hydrogen electroproduction is considerably expensive, so promoting the development of new non-noble catalysts for the cathode of alkaline electrolyzers appears as a suitable way to reduce the costs of this technology. In this sense, a series of tungsten-based carbide materials have been synthesized by the urea-glass route as candidates to improve the HER in alkaline media. Moreover, two different pyridinium-based ionic liquids were employed to modify the surface of the carbide grains and control the amount and nature of their surface species. The main results indicate that the catalyst surface composition is modified in the hybrid materials, which are then distinguished by the appearance of tungsten suboxide structures. This implies the action of ionic liquids as reducing agents. Consequently, differential electrochemical mass spectrometry (DEMS) is used to precisely determine the onset potentials and rate-determining steps (RDS) for the HER in alkaline media. Remarkably, the modified surfaces show high catalytic performance (overpotentials between 45 and 60 mV) and RDS changes from Heyrovsky-Volmer to Heyrovsky as the surface oxide structures get reduced. H2O molecule reduction is then faster at tungsten suboxide, which allows the formation of the adsorbed hydrogen at the surface, boosting the catalytic activity and the kinetics of the alkaline HER.

Incidence of Drug-Induced Delirium During Treatment With Antidepressants or Antipsychotics: A Drug Surveillance Report of German-Speaking Countries Between 1993 and 2016.

OBJECTIVES: Successful treatment of delirium depends on the detection of the reversible contributors. Drugs with delirogenic properties are the most prevalent reversible cause of delirium. METHODS: This observational study is based on data from Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries recording severe adverse drug reactions (ADRs) in psychiatric inpatients. The present study analyzes drug-induced delirium (DID) during treatment with antidepressants and antipsychotics. RESULTS: A total of 436 565 psychiatric inpatients were treated with antidepressants and/or antipsychotics during the observation period from 1993 to 2016 in the participating 110 hospitals. Overall, 254 cases (0.06% of all patients treated with antidepressants and/or antipsychotics) of DID were detected. Implicated either in combination or alone (multiple drugs were implicated in 70.1% of DID), clomipramine (0.24%), amitriptyline (0.21%), and clozapine (0.18%) showed the highest incidence rates of DID. When implicated alone (98 cases overall), clozapine (0.11%) followed by amitriptyline (0.05%) were most likely causally associated with the occurrence of DID. Drugs with strong antimuscarinic properties generally exhibited higher risk of DID. CONCLUSIONS: With an incidence rate of <0.1%, the use of antidepressants and antipsychotics was rarely associated with DID within the Arzneimittelsicherheit in der Psychiatrie program. Tricyclic antidepressants and clozapine were the most commonly implicated psychotropic drugs. These data support the specific role of antimuscarinic properties in DID.

Escitalopram administration, relearning, and neuroplastic effects: A diffusion tensor imaging study in healthy individuals.

BACKGROUND: Neuroplastic processes are influenced by serotonergic agents, which reportedly alter white matter microstructure in humans in conjunction with learning. The goal of this double-blind, placebo-controlled imaging study was to investigate the neuroplastic properties of escitalopram and cognitive training on white matter plasticity during (re)learning as a model for antidepressant treatment and environmental factors. METHODS: Seventy-one healthy individuals (age=25.6 ± 5.0, 43 females) underwent three diffusion magnetic resonance imaging scans: at baseline, after 3 weeks of associative learning (emotional/non-emotional content), and after relearning shuffled associations for an additional 3 weeks. During the relearning phase, participants received a daily dose of 10 mg escitalopram or placebo orally. Fractional anisotropy (FA), and mean (MD), axial (AD), and radial diffusivity (RD) were calculated within the FMRIB software library and analyzed using tract-based spatial statistics. RESULTS: In a three-way repeated-measures marginal model with sandwich estimator standard errors, we found no significant effects of escitalopram and content on AD, FA, MD, and RD during both learning and relearning periods (pFDR>0.05). When testing for escitalopram or content effects separately, we also demonstrated no significant findings (pFDR>0.05) for any of the diffusion tensor imaging metrics. LIMITATIONS: The intensity of the study interventions might have been too brief to induce detectable white matter changes. DISCUSSION: Previous studies examining the effects of SSRIs on white matter tracts in humans have yielded inconclusive outcomes. Our results indicate that relearning under escitalopram does not affect the white matter microstructures in healthy individuals when administered for 3 weeks.

Coexpression of Gene Transcripts with Monoamine Oxidase A Quantified by Human In Vivo Positron Emission Tomography.

The monoamine oxidase A (MAO-A) is integral to monoamine metabolism and is thus relevant to the pathophysiology of various neuropsychiatric disorders; however, associated gene-enzyme relations are not well understood. This study aimed to unveil genes coexpressed with MAO-A. Therefore, 18 179 mRNA expression maps (based on the Allen Human Brain Atlas) were correlated with the cerebral distribution volume (VT) of MAO-A assessed in 36 healthy subjects (mean age ± standard deviation: 32.9 ± 8.8 years, 18 female) using [11C]harmine positron emission tomography scans. Coexpression analysis was based on Spearman's ρ, over-representation tests on Fisher's exact test with false discovery rate (FDR) correction. The analysis revealed 35 genes in cortex (including B-cell translocation gene family, member 3, implicated in neuroinflammation) and 247 genes in subcortex (including kallikrein-related peptidase 10, implicated in Alzheimer's disease). Significantly over-represented Gene Ontology terms included "neuron development", "neuron differentiation", and "cell-cell signaling" as well as "axon" and "neuron projection". In vivo MAO-A enzyme distribution and MAOA expression did not correlate in cortical areas (ρ = 0.08) while correlation was found in subcortical areas (ρ = 0.52), suggesting influences of region-specific post-transcriptional and -translational modifications. The herein reported information could contribute to guide future genetic studies, deepen the understanding of associated pathomechanisms and assist in the pursuit of novel therapeutic targets.

Neuroplastic effects of a selective serotonin reuptake inhibitor in relearning and retrieval.

Animal studies using selective serotonin reuptake inhibitors (SSRIs) and learning paradigms have demonstrated that serotonin is important for flexibility in executive functions and learning. SSRIs might facilitate relearning through neuroplastic processes and thus exert their clinical effects in psychiatric diseases where cognitive functioning is affected. However, translation of these mechanisms to humans is missing. In this randomized placebo-controlled trial, we assessed functional brain activation during learning and memory retrieval in healthy volunteers performing associative learning tasks aiming to translate facilitated relearning by SSRIs. To this extent, seventy-six participants underwent three MRI scanning sessions: (1) at baseline, (2) after three weeks of daily associative learning and subsequent retrieval (face-matching or Chinese character-noun matching) and (3) after three weeks of relearning under escitalopram (10 mg/day) or placebo. Associative learning and retrieval tasks were performed during each functional MRI (fMRI) session. Statistical modeling was done using a repeated-measures ANOVA, to test for content-by-treatment-by-time interaction effects. During the learning task, a significant substance-by-time interaction was found in the right insula showing a greater deactivation in the SSRI cohort after 21 days of relearning compared to the learning phase. In the retrieval task, there was a significant content-by-time interaction in the left angular gyrus (AG) with an increased activation in face-matching compared to Chinese-character matching for both learning and relearning phases. A further substance-by-time interaction was found in task performance after 21 days of relearning, indicating a greater decrease of performance in the placebo group. Our findings that escitalopram modulate insula activation demonstrates successful translation of relearning as a mechanism of SSRIs in human. Furthermore, we show that the left AG is an active component of correct memory retrieval, which coincides with previous literature. We extend the function of this region by demonstrating its activation is not only stimulus dependent but also time constrained. Finally, we were able to show that escitalopram aids in relearning, irrespective of content.

[Biopsy of musculoskeletal tumors : Complications and avoidable errors]. / Biopsie muskuloskeletaler Tumoren : Komplikationen und vermeidbare Fehler.

Biopsy followed by histopathological assessment is the key procedure to establish the correct diagnosis of unclear bone or soft tissue tumors. There are several possibilities to obtain a biopsy specimen. The indication for biopsy should be established in a specialized center, as should the type of biopsy (fine needle, incisional, excisional, percutaneous CT-guided/navigated biopsy), which must be performed according to established guidelines. The tumor biopsy must be representative and adequate in terms of quantity, to enable a conclusive histopathological diagnosis and planning of appropriate treatment. For the correct biopsy tract, the surgical approach for definitive resection must be considered; thus, biopsy should be conducted in the center where the subsequent resection will be performed. Of note, patients whose biopsy is performed at a specialized musculoskeletal tumor center benefit in terms of improved local tumor control.

Massive in Silico Study of Noble Gas Binding to the Structural Proteome.

Noble gases are chemically inert, and it was therefore thought they would have little effect on biology. Paradoxically, it was found that they do exhibit a wide range of biological effects, many of which are target-specific and potentially useful and some of which have been demonstrated in vivo. The underlying mechanisms by which useful pharmacology, such as tissue and neuroprotection, anti-addiction effects, and analgesia, is elicited are relatively unexplored. Experiments to probe the interactions of noble gases with specific proteins are more difficult with gases than those with other chemicals. It is clearly impractical to conduct the large number of gas-protein experiments required to gain a complete picture of noble gas biology. Given the simplicity of atoms as ligands, in silico methods provide an opportunity to gain insight into which noble gas-protein interactions are worthy of further experimental or advanced computational investigation. Our previous validation studies showed that in silico methods can accurately predict experimentally determined noble gas binding sites in X-ray structures of proteins. Here, we summarize the largest reported in silico reverse docking study involving 127 854 protein structures and the five nonradioactive noble gases. We describe how these computational screening methods are implemented, summarize the main types of interactions that occur between noble gases and target proteins, describe how the massive data set that this study generated can be analyzed (freely available at group18.csiro.au), and provide the NDMA receptor as an example of how these data can be used to understand the molecular pharmacology underlying the biology of the noble gases. We encourage chemical biologists to access the data and use them to expand the knowledge base of noble gas pharmacology, and to use this information, together with more efficient delivery systems, to develop "atomic drugs" that can fully exploit their considerable and relatively unexplored potential in medicine.

[Management of complications following tumor endoprosthetic replacement]. / Komplikationsmanagement nach Tumorendoprothesen.

BACKGROUND: Tumor endoprostheses are available as modular systems with which bone defects can be partially reconstructed, usually close to the joints, or as a total replacement of long tubular bones. As a result of continuously improved survival times, they are used with bone tumors, skeletal metastases and, increasingly, in revision arthroplasty. OBJECTIVES: Presentation of the most common complications of tumor endoprostheses and a description of their management, including treatment recommendations. MATERIALS AND METHODS: The current knowledge and our own experience of complication management with the use of megaprostheses are presented. RESULTS: The number of tumor endoprostheses procedures is limited, so that a limited number of studies and classifications are available. Periprosthetic infections involving the soft tissues represent the most serious failure after perioperative dying and local recurrence of the tumor. Two-stage revision remains the gold standard in periprosthetic infection, even if one-stage revision is justifiable in selective indications. Periprosthetic infection and local recurrence is associated with the risk of secondary amputations. Mechanical failure can be treated more easily. Specific socket systems for proximal femoral replacement and attachment tubing allow for adequate soft tissue reconstruction, restoration of joint function, and minimize the risk of dislocation. CONCLUSIONS: In comparison to primary arthroplasty, the risk of failure following tumor endoprosthetic replacement is increased but is basically controllable by revision surgery.

Heritable variation in circulating glucocorticoids and endocrine flexibility in a free-living songbird.

Phenotypic flexibility is a central way that organisms cope with challenging and changing environments. As endocrine signals mediate many phenotypic traits, heritable variation in hormone levels, or their context-dependent flexibility, could present an important target for selection. Several studies have estimated the heritability of circulating glucocorticoid levels under acute stress conditions, but little is known about the potential for either baseline hormone levels or rapid endocrine flexibility to evolve. Here, we assessed the potential for selection to operate on the elevation (circulating hormone levels) and flexibility of glucocorticoid reaction norms to acute restraint stress. Multivariate animal models revealed low but significant heritability in baseline (h2  = 0.13-0.14) and stress-induced glucocorticoids (h2  = 0.18), and moderate heritability in glucocorticoid flexibility in response to acute stress (h2  = 0.38) in free-living juvenile tree swallows (Tachycineta bicolor; n = 408). Baseline glucocorticoids were not genetically correlated with either stress-induced glucocorticoids or glucocorticoid flexibility. These findings indicate that baseline glucocorticoids and the acute stress response are distinct traits that can be independently shaped by selection. Microevolutionary changes that influence the expression or flexibility of these endocrine mediators of phenotype may be an important way that populations adapt to changing environments and novel threats.

Prevention of seasonal affective disorder in daily clinical practice: results of a survey in German-speaking countries.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonally recurrent type of major depression. This predictable aspect makes it promising for preventive treatment. However, evidence for the efficacy and harm of preventive treatment of SAD is scarce, as are recommendations from clinical practice guidelines. The aim of this study was to assess the current use of preventive treatment of SAD in clinical practice in German-speaking countries for the first time. METHODS: We conducted a postal and web-based survey sent to the heads of all psychiatric institutions listed in the inventory "Deutsches Krankenhaus Adressbuch, 2015" that contains all psychiatric hospitals in Germany, Austria, and Switzerland. RESULTS: One hundred institutions (out of 533 institutions, 19%), which treated in total more than 3100 SAD patients in the years 2014/2015, responded. Of those, 81 reported recommending preventive treatment to patients with a history of SAD. There was no consensus on the optimal starting point for preventive treatment. Most of the institutions that implemented prevention of SAD, recommended lifestyle changes (85%), antidepressants (84%), psychotherapy (73%), and light therapy (72%) to their patients. The situation was similar in northern and southern regions. CONCLUSIONS: Most hospitals recommended the use of preventive treatment to SAD patients, although evidence on efficacy and harm is limited. A wide variety of interventions were recommended, although guidelines only include recommendations for acute treatment. To assist psychiatrists and patients in future decision making, controlled studies on preventive treatment for SAD that compare different interventions with one another are needed.

Association of Protein Distribution and Gene Expression Revealed by PET and Post-Mortem Quantification in the Serotonergic System of the Human Brain.

Regional differences in posttranscriptional mechanisms may influence in vivo protein densities. The association of positron emission tomography (PET) imaging data from 112 healthy controls and gene expression values from the Allen Human Brain Atlas, based on post-mortem brains, was investigated for key serotonergic proteins. PET binding values and gene expression intensities were correlated for the main inhibitory (5-HT1A) and excitatory (5-HT2A) serotonin receptor, the serotonin transporter (SERT) as well as monoamine oxidase-A (MAO-A), using Spearman's correlation coefficients (rs) in a voxel-wise and region-wise analysis. Correlations indicated a strong linear relationship between gene and protein expression for both the 5-HT1A (voxel-wise rs = 0.71; region-wise rs = 0.93) and the 5-HT2A receptor (rs = 0.66; 0.75), but only a weak association for MAO-A (rs = 0.26; 0.66) and no clear correlation for SERT (rs = 0.17; 0.29). Additionally, region-wise correlations were performed using mRNA expression from the HBT, yielding comparable results (5-HT1Ars = 0.82; 5-HT2Ars = 0.88; MAO-A rs = 0.50; SERT rs = -0.01). The SERT and MAO-A appear to be regulated in a region-specific manner across the whole brain. In contrast, the serotonin-1A and -2A receptors are presumably targeted by common posttranscriptional processes similar in all brain areas suggesting the applicability of mRNA expression as surrogate parameter for density of these proteins.

Imaging the neuroplastic effects of ketamine with VBM and the necessity of placebo control.

In the last years a plethora of studies have investigated morphological changes induced by behavioural or pharmacological interventions using structural T1-weighted MRI and voxel-based morphometry (VBM). Ketamine is thought to exert its antidepressant action by restoring neuroplasticity. In order to test for acute impact of a single ketamine infusion on grey matter volume we performed a placebo-controlled, double-blind investigation in healthy volunteers using VBM. 28 healthy individuals underwent two MRI sessions within a timeframe of 2 weeks, each consisting of two structural T1-weighted MRIs within a single session, one before and one 45min after infusion of S-ketamine (bolus of 0.11mg/kg, followed by an maintenance infusion of 0.12mg/kg) or placebo (0.9% NaCl infusion) using a crossover design. In the repeated-measures ANOVA with time (post-infusion/pre-infusion) and medication (placebo/ketamine) as factors, no significant effect of interaction and no effect of medication was found (FWE-corrected). Importantly, further post-hoc t-tests revealed a strong "decrease" of grey matter both in the placebo and the ketamine condition over time. This effect was evident mainly in frontal and temporal regions bilaterally with t-values ranging from 4.95 to 5.31 (FWE-corrected at p<0.05 voxel level). The vulnerabilities of VBM have been repeatedly demonstrated, with reports of influence of blood flow, tissue water and direct effects of pharmacological compounds on the MRI signal. Here again, we highlight that the relationship between intervention and VBM results is apparently subject to a number of physiological influences, which are partly unknown. Future studies focusing on the effects of ketamine on grey matter should try to integrate known influential factors such as blood flow into analysis. Furthermore, the results of this study highlight the importance of a carefully performed placebo condition in pharmacological fMRI studies.

Gender transition affects neural correlates of empathy: A resting state functional connectivity study with ultra high-field 7T MR imaging.

Sex-steroid hormones have repeatedly been shown to influence empathy, which is in turn reflected in resting state functional connectivity (rsFC). Cross-sex hormone treatment in transgender individuals provides the opportunity to examine changes to rsFC over gender transition. We aimed to investigate whether sex-steroid hormones influence rsFC patterns related to unique aspects of empathy, namely emotion recognition and description as well as emotional contagion. RsFC data was acquired with 7Tesla magnetic resonance imaging in 24 male-to-female (MtF) and 33 female-to-male (FtM) transgender individuals before treatment, in addition to 33 male- and 44 female controls. Of the transgender participants, 15 MtF and 20 FtM were additionally assessed after 4 weeks and 4 months of treatment. Empathy scores were acquired at the same time-points. MtF differed at baseline from all other groups and assimilated over the course of gender transition in a rsFC network around the supramarginal gyrus, a region central to interpersonal emotion processing. While changes to sex-steroid hormones did not correlate with rsFC in this network, a sex hormone independent association between empathy scores and rsFC was found. Our results underline that 1) MtF transgender persons demonstrate unique rsFC patterns in a network related to empathy and 2) changes within this network over gender transition are likely related to changes in emotion recognition, -description, and -contagion, and are sex-steroid hormone independent.

Co-expression of truncated and full-length tau induces severe neurotoxicity.

Abundant tau inclusions are a defining hallmark of several human neurodegenerative diseases, including Alzheimer's disease. Protein fragmentation is a widely observed event in neurodegenerative proteinopathies. The relevance of tau fragmentation for the neurodegenerative process in tauopathies has yet remained unclear. Here we found that co-expression of truncated and full-length human tau in mice provoked the formation of soluble high-molecular-weight tau, the failure of axonal transport, clumping of mitochondria, disruption of the Golgi apparatus and missorting of synaptic proteins. This was associated with extensive nerve cell dysfunction and severe paralysis by the age of 3 weeks. When the expression of truncated tau was halted, most mice recovered behaviorally and functionally. In contrast, co-expression of full-length tau isoforms did not result in paralysis. Truncated tau thus induces extensive but reversible neurotoxicity in the presence of full-length tau through the formation of nonfilamentous high-molecular-weight tau aggregates, in the absence of tau filaments. Targeting tau fragmentation may provide a novel approach for the treatment of human tauopathies.

Revisiting adult neurogenesis and the role of erythropoietin for neuronal and oligodendroglial differentiation in the hippocampus.

Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression and bipolar disease. This consistent EPO effect on cognition is independent of its role in hematopoiesis. The cellular mechanisms of action in brain, however, have remained unclear. Here we studied healthy young mice and observed that 3-week EPO administration was associated with an increased number of pyramidal neurons and oligodendrocytes in the hippocampus of ~20%. Under constant cognitive challenge, neuron numbers remained elevated until >6 months of age. Surprisingly, this increase occurred in absence of altered cell proliferation or apoptosis. After feeding a 15N-leucine diet, we used nanoscopic secondary ion mass spectrometry, and found that in EPO-treated mice, an equivalent number of neurons was defined by elevated 15N-leucine incorporation. In EPO-treated NG2-Cre-ERT2 mice, we confirmed enhanced differentiation of preexisting oligodendrocyte precursors in the absence of elevated DNA synthesis. A corresponding analysis of the neuronal lineage awaits the identification of suitable neuronal markers. In cultured neurospheres, EPO reduced Sox9 and stimulated miR124, associated with advanced neuronal differentiation. We are discussing a resulting working model in which EPO drives the differentiation of non-dividing precursors in both (NG2+) oligodendroglial and neuronal lineages. As endogenous EPO expression is induced by brain injury, such a mechanism of adult neurogenesis may be relevant for central nervous system regeneration.

Epidemiology and socioeconomic impact of seasonal affective disorder in Austria.

BACKGROUND: Seasonal affective disorder (SAD) is a subtype of recurrent depressive or bipolar disorder that is characterized by regular onset and remission of affective episodes at the same time of the year. The aim of the present study was to provide epidemiological data and data on the socioeconomic impact of SAD in the general population of Austria. METHODS: We conducted a computer-assisted telephone interview in 910 randomly selected subjects (577 females and 333 males) using the Seasonal Health Questionnaire (SHQ), the Seasonal Pattern Assessment Questionnaire (SPAQ), and the Sheehan Disability Scale (SDS). Telephone numbers were randomly drawn from all Austrian telephone books and transformed using the random last digits method. The last birthday method was employed to choose the target person for the interviews. RESULTS: Out of our subjects, 2.5% fulfilled criteria for the seasonal pattern specifier according to DSM-5 and 2.4% (95% CI=1.4-3.5%) were diagnosed with SAD. When applying the ICD-10 criteria 1.9% (95% CI=0.9-2.8%) fulfilled SAD diagnostic criteria. The prevalence of fall-winter depression according to the Kasper-Rosenthal criteria was determined to be 3.5%. The criteria was fulfilled by 15.1% for subsyndromal SAD (s-SAD). We did not find any statistically significant gender differences in prevalence rates. When using the DSM-5 as a gold standard for the diagnosis of SAD, diagnosis derived from the SPAQ yielded a sensitivity of 31.8% and a specificity of 97.2%. Subjects with SAD had significantly higher scores on the SDS and higher rates of sick leave and days with reduced productivity than healthy subjects. CONCLUSIONS: Prevalence estimates for SAD with the SHQ are lower than with the SPAQ. Our data are indicative of the substantial burden of disease and the socioeconomic impact of SAD. This epidemiological data shows a lack of gender differences in SAD prevalence. The higher rates of females in clinical SAD samples might, at least in part, be explained by lower help seeking behaviour in males.

Highly Sensitive and Efficient Screening of Streptococcus Agalactiae Through Improved Real-Time PCR Protocols and Optimized Analytical Parameters.

BACKGROUND: The detection of Streptococcus agalactiae colonization during pregnancy is important in order to prevent neonatal infections and reduce mortality rates. METHODS: A highly sensitive (up to 1,000 UFC/mL), fully automated, and cost effective cylB specific real-time PCR protocol was developed for the detection of S. agalactiae in anal and vaginal swabs of pregnant women. RESULTS: From the 62 test subjects, 24 were considered positive by PCR (38%) and 14 by culture (24%; p = 0.0015). CONCLUSIONS: The observed discrepancies and the reduced turnaround time justifies molecular screening for S. agalactiae.

Experimental Study of Spectral Properties of a Frenkel-Kontorova System.

We report on microwave emission from linear parallel arrays of underdamped Josephson junctions, which are described by the Frenkel-Kontorova (FK) model. Electromagnetic radiation is detected from the arrays when biased on current singularities (steps) appearing at voltages V(n)=Φ(0)(nc̅/L), where Φ(0)=2.07×10(-15) Wb is the magnetic flux quantum, and c̅, L, and n are, respectively, the speed of light in the transmission line embedding the array, L its physical length, and n an integer. The radiation, detected at fundamental frequency c̅/2L when biased on different singularities, indicates shuttling of bunched 2π kinks (magnetic flux quanta). Resonance of flux-quanta motion with the small-amplitude oscillations induced in the arrays gives rise to fine structures in the radiation spectrum, which are interpreted on the basis of the FK model describing the resonance. The impact of our results on design and performances of new digital circuit families is discussed.