Fast Ultrahigh-Density Writing of Low Conductivity Patterns on Semiconducting Polymers

The exceptional interest in improving the limitations of data storage, molecular electronics, and optoelectronics has promoted the development of an ever increasing number of techniques used to pattern polymers at micro and nanoscale. Most of them rely on Atomic Force Microscopy to thermally or electrostatically induce mass transport, thereby creating topographic features. Here we show that the mechanical interaction of the tip of the Atomic Force Microscope with the surface of a class of conjugate polymers produces a local increase of molecular disorder, inducing a localized lowering of the semiconductor conductivity, not associated to detectable modifications in the surface topography. This phenomenon allows for the swift production of low conductivity patterns on the polymer surface at an unprecedented speed exceeding 20 $\mu m s^{-1}$; paths have a resolution in the order of the tip size (20 nm) and are detected by a Conducting-Atomic Force Microscopy tip in the conductivity maps.Comment: 22 pages, 6 figures, published in Nature Communications as Article (8 pages

Rubbing effects on the structural and optical properties of poly(3­hexylthiophene) films

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Optimizing transcranial magnetic stimulation for spaceflight applications

As space agencies aim to reach and build installations on Mars, the crews will face longer exposure to extreme environments that may compromise their health and performance. Transcranial magnetic stimulation (TMS) is a painless non-invasive brain stimulation technique that could support space exploration in multiple ways. However, changes in brain morphology previously observed after long-term space missions may impact the efficacy of this intervention. We investigated how to optimize TMS for spaceflight-associated brain changes. Magnetic resonance imaging T1-weighted scans were collected from 15 Roscosmos cosmonauts and 14 non-flyer participants before, after 6 months on the International Space Station, and at a 7-month follow-up. Using biophysical modeling, we show that TMS generates different modeled responses in specific brain regions after spaceflight in cosmonauts compared to the control group. Differences are related to spaceflight-induced structural brain changes, such as those impacting cerebrospinal fluid volume and distribution. We suggest solutions to individualize TMS to enhance its efficacy and precision for potential applications in long-duration space missions. © 2023, The Author(s)

Juvenile moyamoya and craniosynostosis in a child with deletion 1p32p31: Expanding the clinical spectrum of 1p32p31 deletion syndrome and a review of the literature

Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterised by the progressive occlusion of the internal carotid artery. Its aetiology is uncertain, but a genetic background seems likely, given the high MA familial rate. To investigate the aetiology of craniosynostosis and juvenile moyamoya in a 14-year-old male patient, we performed an array-comparative genomic hybridisation revealing a de novo interstitial deletion of 8.5 Mb in chromosome region 1p32p31. The deletion involved 34 protein coding genes, including NF1A, whose haploinsufficiency is indicated as being mainly responsible for the 1p32-p31 chromosome deletion syndrome phenotype (OMIM 613735). Our patient also has a deleted FOXD3 of the FOX gene family of transcription factors, which plays an important role in neural crest cell growth and differentiation. As the murine FOXD3-/- model shows craniofacial anomalies and abnormal common carotid artery morphology, it can be hypothesised that FOXD3 is involved in the pathogenesis of the craniofacial and vascular defects observed in our patient. In support of our assumption, we found in the literature another patient with a syndromic form of MA who had a deletion involving another FOX gene (FOXC1). In addition to describing the clinical history of our patient, we have reviewed all of the available literature concerning other patients with a 1p32p31 deletion, including cases from the Decipher database, and we have also reviewed the genetic disorders associated with MA, which is a useful guide for the diagnosis of syndromic form of MA

Local and Distributed fMRI Changes Induced by 40 Hz Gamma tACS of the Bilateral Dorsolateral Prefrontal Cortex: A Pilot Study

Over the past few years, the possibility of modulating fast brain oscillatory activity in the gamma (γ) band through transcranial alternating current stimulation (tACS) has been discussed in the context of both cognitive enhancement and therapeutic scenarios. However, the effects of tACS targeting regions outside the motor cortex, as well as its spatial specificity, are still unclear. Here, we present a concurrent tACS-fMRI block design study to characterize the impact of 40 Hz tACS applied over the left and right dorsolateral prefrontal cortex (DLPFC) in healthy subjects. Results suggest an increase in blood oxygenation level-dependent (BOLD) activity in the targeted bilateral DLPFCs, as well as in surrounding brain areas affected by stimulation according to biophysical modeling, i.e., the premotor cortex and anterior cingulate cortex (ACC). However, off-target effects were also observed, primarily involving the visual cortices, with further effects on the supplementary motor areas (SMA), left subgenual cingulate, and right superior temporal gyrus. The specificity of 40 Hz tACS over bilateral DLPFC and the possibility for network-level effects should be considered in future studies, especially in the context of recently promoted gamma-induction therapeutic protocols for neurodegenerative disorders. © 2022 Lucia Mencarelli et al

Regional Precuneus Cortical Hyperexcitability in Alzheimer's Disease Patients

Objective: Neuronal excitation/inhibition (E/I) imbalance is a potential cause of neuronal network malfunctioning in Alzheimer's disease (AD), contributing to cognitive dysfunction. Here, we used a novel approach combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to probe cortical excitability in different brain areas known to be directly involved in AD pathology. Methods: We performed TMS-EEG recordings targeting the left dorsolateral prefrontal cortex (l-DLPFC), the left posterior parietal cortex (l-PPC), and the precuneus (PC) in a large sample of patients with mild-to-moderate AD (n = 65) that were compared with a group of age-matched healthy controls (n = 21). Results: We found that patients with AD are characterized by a regional cortical hyperexcitability in the PC and, to some extent, in the frontal lobe, as measured by TMS-evoked potentials. Notably, cortical excitability assessed over the l-PPC was comparable between the 2 groups. Furthermore, we found that the individual level of PC excitability was associated with the level of cognitive impairment, as measured with Mini-Mental State Examination, and with corticospinal fluid levels of Aβ42 . Interpretation: Our data provide novel evidence that precuneus cortical hyperexcitability is a key feature of synaptic dysfunction in patients with AD. The current results point to the combined approach of TMS and EEG as a novel promising technique to measure hyperexcitability in patients with AD. This index could represent a useful biomarker to stage disease severity and evaluate response to novel therapies. ANN NEUROL 2022

Graphene-based waveguide resonators for submillimeter-wave applications

Utilization of graphene covered waveguide inserts to form tunable waveguide resonators is theoretically explained and rigorously investigated by means of full-wave numerical electromagnetic simulations. Instead of using graphene-based switching elements, the concept we propose incorporates graphene sheets as parts of a resonator. Electrostatic tuning of the graphene surface conductivity leads to changes in the electromagnetic field boundary conditions at the resonator edges and surfaces, thus producing an effect similar to varying the electrical length of a resonator. The presented outline of the theoretical background serves to give phenomenological insight into the resonator behavior, but it can also be used to develop customized software tools for design and optimization of graphene-based resonators and filters. Due to the linear dependence of the imaginary part of the graphene surface impedance on frequency, the proposed concept was expected to become effective for frequencies above 100 GHz, which is confirmed by the numerical simulations. A frequency range from 100 GHz up to 1100 GHz, where the rectangular waveguides are used, is considered. Simple, all-graphene-based resonators are analyzed first, to assess the achievable tunability and to check the performance throughout the considered frequency range. Graphene–metal combined waveguide resonators are proposed in order to preserve the excellent quality factors typical for the type of waveguide discontinuities used. Dependence of resonator properties on key design parameters is studied in detail. Dependence of resonator properties throughout the frequency range of interest is studied using eight different waveguide sections appropriate for different frequency intervals. Proposed resonators are aimed at applications in the submillimeter-wave spectral region, serving as the compact tunable components for the design of bandpass filters and other devices

Usefulness and limitations of comprehensive characterization of mRNA splicing profiles in the definition of the clinical relevance of BRCA1/2 variants of uncertain significance

Highly penetrant variants of BRCA1/2 genes are involved in hereditary predisposition to breast and ovarian cancer. The detection of pathogenic BRCA variants has a considerable clinical impact, allowing appropriate cancer-risk management. However, a major drawback is represented by the identification of variants of uncertain significance (VUS). Many VUS potentially affect mRNA splicing, making transcript analysis an essential step for the definition of their pathogenicity. Here, we characterize the impact on splicing of ten BRCA1/2 variants. Aberrant splicing patterns were demonstrated for eight variants whose alternative transcripts were fully characterized. Different events were observed, including exon skipping, intron retention, and usage of de novo and cryptic splice sites. Transcripts with premature stop codons or in-frame loss of functionally important residues were generated. Partial/complete splicing effect and quantitative contribution of different isoforms were assessed, leading to variant classification according to Evidence-based Network for the Interpretation of Mutant Alleles (ENIGMA) consortium guidelines. Two variants could be classified as pathogenic and two as likely benign, while due to a partial splicing effect, six variants remained of uncertain significance. The association with an undefined tumor risk justifies caution in recommending aggressive risk-reduction treatments, but prevents the possibility of receiving personalized therapies with potential beneficial effect. This indicates the need for applying additional approaches for the analysis of variants resistant to classification by gene transcript analyses