Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual-Site Transcranial Magnetic Stimulation for the Treatment of Parkinson's Disease

Abnormal oscillatory activity in the subthalamic nucleus (STN) may be relevant for motor symptoms in Parkinson's disease (PD). Apart from deep brain stimulation, transcranial magnetic stimulation (TMS) may be suitable for altering these oscillations. We speculated that TMS to different cortical areas (primary motor cortex, M1, and dorsal premotor cortex, PMd) may activate neuronal subpopulations within the STN via corticofugal neurons projecting directly to the nucleus. We hypothesized that PD symptoms can be ameliorated by a lasting decoupling of STN neurons by associative dual-site repetitive TMS (rTMS). Associative dual-site rTMS (1 Hz) directed to PMd and M1 (“ADS-rTMS”) was employed in 20 PD patients treated in a blinded, placebo-controlled cross-over design. Results: No adverse events were noted. We found no significant improvement in clinical outcome parameters (videography of MDS-UPDRS-III, finger tapping, spectral tremor power). Variation of the premotor stimulation site did not induce beneficial effects either. A single session of ADS-rTMS was tolerated well, but did not produce a clinically meaningful benefit on Parkinsonian motor symptoms. Successful treatment using TMS targeting subcortical nuclei may require an intervention over several days or more detailed physiological information about the individual brain state and stimulation-induced subcortical effects.
Regulatory Factors for tRNA Modifications in Extreme- Thermophilic Bacterium Thermus thermophilus

Thermus thermophilus is an extreme-thermophilic bacterium that can grow at a wide range of temperatures (50–83°C). To enable T. thermophilus to grow at high temperatures, several biomolecules including tRNA and tRNA modification enzymes show extreme heat-resistance. Therefore, the modified nucleosides in tRNA from T. thermophilus have been studied mainly from the view point of tRNA stabilization at high temperatures. Such studies have shown that several modifications stabilize the structure of tRNA and are essential for survival of the organism at high temperatures. Together with tRNA modification enzymes, the modified nucleosides form a network that regulates the extent of different tRNA modifications at various temperatures. In this review, I describe this network, as well as the tRNA recognition mechanism of individual tRNA modification enzymes. Furthermore, I summarize the roles of other tRNA stabilization factors such as polyamines and metal ions.
Biomarkers for Dementia, Fatigue, and Depression in Parkinson's Disease

Parkinson's disease is a common multisystem neurodegenerative disorder characterized by typical motor and non-motor symptoms. There is an urgent need for biomarkers for assessment of disease severity, complications and prognosis. In addition, biomarkers reporting the underlying pathophysiology assist in understanding the disease and developing neuroprotective therapies. Ultimately, biomarkers could be used to develop a more efficient personalized approach for clinical trials and treatment strategies. With the goal to improve quality of life in Parkinson's disease it is essential to understand and objectively monitor non-motor symptoms. This narrative review provides an overview of recent developments of biomarkers (biofluid samples and imaging) for three common neuropsychological syndromes in Parkinson's disease: dementia, fatigue, and depression.
Associations Between Behavioral Effects of Bisphenol A and DNA Methylation in Zebrafish Embryos

Endocrine-disrupting contaminants have been associated with aberrant changes in epigenetic pathways in animals. In this study, zebrafish embryos were exposed bisphenol A (BPA) to search for associations between behavior and epigenetic mechanisms in fish. For concentration-dependent responses, embryos were exposed to a range of BPA concentrations (0.1 nM to 30 μM). Embryos were analyzed for locomotor activity at 3-, 4-, and 5-days post fertilization (dpf) in response to changing light conditions. Based on concentration-dependent effects on behavior and gene expression, 10 μM BPA [from 24 to 96 hours post fertilization (hpf)] was used for a whole-genome bisulfite sequencing (WGBS) study searching for genome-wide impacts on DNA methylation. Over the examined concentration ranges, hyperactivity was demonstrated for exposures to 0.001 μM BPA in comparison to embryos exposed to lower or higher BPA concentrations. Transcriptional analysis showed significant effects at >0.01 μM BPA for two genes related to DNA methylation (dnmt1, cbs). BPA exposure did not significantly affect global DNA methylation, but 20,474 differentially methylated (DM) sites in 4,873 genes were identified by WGBS analysis. Most DM sites were identified within gene bodies. The genes with the most DM sites were all protocadherin 2 gamma subfamily genes, related to axon targeting, synaptic development and neuronal survival. KEGG pathways most significantly affected by BPA exposure were phosphatidylinositol signaling system, followed by VEGF and MAPK signaling pathways. This study shows that BPA can affect zebrafish embryo swimming activity at very low concentrations as well as affecting numerous methylated sites in genes which are overrepresented in functionally relevant metabolic pathways. In conclusion, altered methylation patterns of genes associated with nervous system development might lead to abnormal swimming activity.
Time of Emergence of Surface Ocean Carbon Dioxide Trends in the North American Coastal Margins in Support of Ocean Acidification Observing System Design

Time of Emergence (ToE) is the time when a signal emerges from the noise of natural variability. Commonly used in climate science for the detection of anthropogenic forcing, this concept has recently been applied to geochemical variables to assess the emerging times of anthropogenic ocean acidification (OA) mostly in the open ocean using global climate and Earth System Models. Yet studies of OA variables are scarce within costal margins, due to limited multidecadal time-series observations of carbon parameters. ToE provides important information for decision making regarding strategic configuration of observing assets to ensure they are optimally positioned either for signal detection and/or process elicitation and to identify the most suitable variables in discerning OA-related changes. Herein, we present a short overview of ToE estimates on an OA variable, CO2 fugacity ƒ(CO2,sw), in the North American ocean margins using coastal data from Surface Ocean CO2 Atlas (SOCAT) V5. ToE suggests an average theoretical timeframe for an OA signal to emerge of 23(±13) years, but with considerable spatial variability. Most coastal areas are experiencing additional secular and/or multi-decadal forcing(s) that modifies the OA signal, and such forcing may not be sufficiently resolved by current observations. We provide recommendations that will help scientists and decision makers design and implement OA monitoring systems in the next decade addressing the objectives of OceanObs19 in support of the United Nations Decade of Ocean Science for Sustainable Development (2021-2030) and the Sustainable Development Goal (SDG) 14.3 Target to “Minimize and address the impacts of OA ”.
Editorial: Deep Learning in Biological, Computer, and Neuromorphic Systems

Deep learning is a branch of machine learning in which statistical representations of the input data, as opposed to task-specific algorithms, are learned. Deep learningmay be supervised, unsupervised, or semi-supervised (Lecun et al., 2015; Schmidhuber, 2015; Goodfellow et al., 2016). Deep learning techniques are behind many impressive recent successes of machine learning; for example, a deep learning machine recently beat the world champion at the game of Go (Silver et al., 2016), a highly significant achievement that had remained out of reach for the past 50 years. The current Research Topic provides a useful overview of the capabilities and the applications of deep learning and of attempts to elucidate some of its general principles. Many of the applications in the current Research Topic focus on various aspects of neurology and neuroscience. For example, Liu et al. use deep learning to distinguish patients with Alzheimer’s disease from healthy controls using PET images; Wang and Ke use an artificial neural network (ANN) to identify epileptic seizures in EEG recordings; Hegdé and Bart use deep learning and deep synthesis to generate artificial but naturalistic mammogram images for psychophysics experiments; and Zhang et al. attempt to perform “mind reading” by reconstructing an image being viewed by a subject based on the subject’s MRI recording. Additional papers address the underpinnings of deep learning as an approach. For example, Wan and Song investigate ways to add hints to a network to improve its performance, and Thiele et al. propose a spiking deep network architecture that is suitable for online deep learning. Finally, Bart and Hegdé investigate the explainability of decisions learned in a weakly guided manner, an issue that is relevant to both biological and artificial learning systems.
Calcium-Phosphate Crystals Promote RANKL Expression via the Downregulation of DUSP1

Osteoarthritis (OA) is a naturally occurring, irreversible disorder and a major health burden. The disease is multifactorial, involving both physiological and mechanical processes, but calcium crystals have been associated intimately with its pathogenesis. This study tested the hypothesis that these crystals have a detrimental effect on the differentiation of osteoclasts and bone homeostasis. This study employed an osteoblast-osteoclast coculture system that resembles in vivo osteoblast-dependent osteoclast differentiation along with Ca2+-phosphate-coated culture dishes. The calcium-containing crystals upregulated the expression of RANKL and increased the differentiation of osteoclasts significantly as a result. On the other hand, osteoblast differentiation was unaffected. MicroRNA profiling showed that dual-specificity phosphatases 1 (DUSP1) was associated with the increased RANKL expression. DUSP1 belongs to a family of MAPK phosphatases and is known to inactivate all three groups of MAPKs, p38, JNK, and ERK. Furthermore, knockdown of DUSP1 gene expression suggested that RANKL expression increases significantly in the absence of DUSP1 regulation. Microarray analysis of the DUSP1 mRNA levels in patients with pathological bone diseases also showed that the downregulated DUSP1 expression leads to increased expression of RANKL and consequently to the destruction of the bone observed in these patients. These findings suggest that calcium-containing crystals may play a crucial role in promoting RANKL-induced osteoclastogenesis via DUSP1.
Heterotypic CAF-tumor spheroids promote early peritoneal metastatis of ovarian cancer

High-grade serous ovarian cancer (HGSOC) is hallmarked by early onset of peritoneal dissemination, which distinguishes it from low-grade serous ovarian cancer (LGSOC). Here, we describe the aggressive nature of HGSOC ascitic tumor cells (ATCs) characterized by integrin &agr;5high (ITGA5high) ATCs, which are prone to forming heterotypic spheroids with fibroblasts. We term these aggregates as metastatic units (MUs) in HGSOC for their advantageous metastatic capacity and active involvement in early peritoneal dissemination. Intriguingly, fibroblasts inside MUs support ATC survival and guide their peritoneal invasion before becoming essential components of the tumor stroma in newly formed metastases. Cancer-associated fibroblasts (CAFs) recruit ITGA5high ATCs to form MUs, which further sustain ATC ITGA5 expression by EGF secretion. Notably, LGSOC is largely devoid of CAFs and the resultant MUs, which might explain its metastatic delay. These findings identify a specialized MU architecture that amplifies the tumor–stroma interaction and promotes transcoelomic metastasis in HGSOC, providing the basis for stromal fibroblast-oriented interventions in hampering OC peritoneal propagation.
The influence of age‐associated comorbidities on responses to combination antiretroviral therapy in older people living with HIV

Multiple comorbidities among HIV‐positive individuals may increase the potential for polypharmacy causing drug‐to‐drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age‐associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age‐associated comorbidities on therapeutic outcomes of cART in HIV‐positive adults in Asian countries.
A rough guide to the non‐coding RNA world of Salmonella

Salmonella species are enterobacterial pathogens that have been exceptionally well investigated with respect to virulence mechanisms, microbial pathogenesis, genome evolution and many fundamental pathways of gene expression and metabolism. While these studies have traditionally focused on protein functions, Salmonella has also become a model organism for RNA‐mediated regulation. The present review is dedicated to the non‐coding RNA world of Salmonella: it covers small RNAs (sRNAs) that act as post‐transcriptional regulators of gene expression, novel Salmonella cis‐regulatory RNA elements that sense metabolite and metal ion concentrations (or temperature), and globally acting RNA‐binding proteins such as CsrA or Hfq (inactivation of which cause drastic phenotypes and virulence defects). Owing to mosaic genome structure, some of the Salmonella sRNAs are widely conserved in bacteria whereas others are very specific to Salmonella species. Intriguingly, sRNAs of either type (CsrB/C, InvR, SgrS) facilitate cross‐talk between the Salmonella core genome and its laterally acquired virulence regions. Work in Salmonella also identified physiological functions (and mechanisms thereof) of RNA that had remained unknown in Escherichia coli, and pioneered the use of high‐throughput sequencing technology to identify the sRNA and mRNA targets of bacterial RNA‐binding proteins.
RecQ DNA helicase HRDC domains are critical determinants in Neisseria gonorrhoeae pilin antigenic variation and DNA repair

Neisseria gonorrhoeae (Gc), an obligate human bacterial pathogen, utilizes pilin antigenic variation to evade host immune defences. Antigenic variation is driven by recombination between expressed (pilE) and silent (pilS) copies of the pilin gene, which encodes the major structural component of the type IV pilus. We have investigated the role of the GcRecQ DNA helicase (GcRecQ) in this process. Whereas the vast majority of bacterial RecQ proteins encode a single ‘Helicase and RNase D C‐terminal’ (HRDC) domain, GcRecQ encodes three tandem HRDC domains at its C‐terminus. Gc mutants encoding versions of GcRecQ with either two or all three C‐terminal HRDC domains removed are deficient in pilin variation and sensitized to UV light‐induced DNA damage. Biochemical analysis of a GcRecQ protein variant lacking two HRDC domains, GcRecQΔHRDC2,3, shows it has decreased affinity for single‐stranded and partial‐duplex DNA and reduced unwinding activity on a synthetic Holliday junction substrate relative to full‐length GcRecQ in the presence of Gc single‐stranded DNA‐binding protein (GcSSB). Our results demonstrate that the multiple HRDC domain architecture in GcRecQ is critical for structure‐specific DNA binding and unwinding, and suggest that these features are central to GcRecQ's roles in Gc antigenic variation and DNA repair.
Of blood, brains and bacteria, the Amt/Rh transporter family: emerging role of Amt as a unique microbial sensor

Members of the Amt/Rh family of transporters are found almost ubiquitously in all forms of life. However, the molecular state of the substrate (NH3 or NH4+) has been the subject of active debate. At least for bacterial Amt proteins, the model emerging from computational, X‐ray crystal and mutational analysis is that NH4+ is deprotonated at the exterior, conducted through the membrane as NH3, and reprotonated at the cytoplasmic interface. A proton concomitantly is transferred from the exterior to the interior, although the mechanism is unclear. Here we discuss recent evidence indicating that an important function of at least some eukaryotic and bacterial Amts is to act as ammonium sensors and regulate cellular metabolism in response to changes in external ammonium concentrations. This is now well documented in the regulation of yeast pseudohyphal development and filamentous growth. As well, membrane sequestration of GlnK, a PII signal transduction protein, by AmtB has been shown to regulate nitrogenase in some diazotrophs, and nitrogen metabolism in some Gram‐positive bacteria. Formation of GlnK–AmtB membrane complexes might have other, as yet undiscovered, regulatory roles. This possibility is emphasized by the discovery in some genomes of genes for chimeric Amts with fusions to various regulatory elements.
On-Board Microgrids for the More Electric Aircraft—Technology Review

This paper presents an overview of technology related to on-board microgrids for the more electric aircraft. All aircraft use an isolated system, where security of supply and power density represents the main requirements. Different distribution systems (ac and dc) and voltage levels coexist, and power converters have the central role in connecting them with high reliability and high power density. Ensuring the safety of supply with a limited redundancy is one of the targets of the system design since it allows increasing the power density. This main challenge is often tackled with proper load management and advanced control strategies, as highlighted in this paper.
Wi-Fi Network Analysis with a Large Number of Access Points

For today, each of us uses wirelesscommunication capabilities. We often use Wi-Fi access points because we need an access to the Internet. This article discusses the security of Wi-Fi wireless networks. The article describes the method of a possible intruder’s attack on one or several wireless networks. This study illustrates the possible scheme of the attacker's actions and the situation of the attack on wireless clients. This method is using the generation of a large number of Wi-Fi access points. The article also includes an analyzing of networks status during an attack and the behavior of wireless clients connected to access points with different configurations.
UWB Balanced BPF Using a Low-Cost LCP Bonded Multilayer PCB Technology

This paper presents a new miniaturized ultra-wideband (UWB) multilayer balanced bandpass filter (BPF) using the liquid-crystal polymer technology. The design is based on the use of two baluns and uses the transversal signal-interference concept for the realization of differential-mode (DM) passband and common-mode (CM) stopband. The broadside coupled stripline structure is adopted in this paper to realize UWB performances and pure TEM mode. The fabricated prototype is self-packaged, light in weight, and cost effective with a small footprint. The demonstrated balanced BPF achieves the excellent DM and CM responses within the entire bandwidth, centered at 6.85 GHz. The simulation and measurement results show good agreement.
Design, Modeling, and Fabrication of a 3-DOF Wrist Rehabilitation Robot

Wrist impairment is a common cause of full/partial functional loss in the elderly. Such impairment may also occur after stroke, sport injuries or spinal cord injuries. A complete treatment process often includes certain rehab exercises after surgery or impairment to increase the wrist muscles tone. Therefore, extensive research has been conducted to design assistive rehab robots and devices to improve the treatment process. In this paper, a wrist rehabilitation robot is developed. The mechanical structure is fabricated based on the design requirements. The dynamic model of the robot is presented following anthropometric data. The final prototype, made at reasonable cost, offers three wrist degrees of freedom (DOF) and major wrist ranges of motion (ROM) required for standard wrist rehabilitation trainings.
Resonant Tunnelling Diodes for next generation THz systems

Resonant tunnelling diodes (RTDs) are a strong candidate for future wireless communications in the THz spectrum (sub-millimetre waves), offering compact, room-temperature operation with the potential to exceed the bit transfer rate mandated by the 12G-SDI standard, using a single wireless link. A free-space RTD emitter operating at 353GHz is described. The fabrication process consists of a dual-pass I-line photolithography & etch technique using an air bridge, allowing low resistivity ohmic contacts, and accurate control of desired device area. With extrinsic circuit elements taken into account, the intrinsic semiconductor efficiency is analysed to investigate structural improvements for radiative efficiency. Such optimised structures are presented, and then characterised after being epitaxially grown with commercially viable metal-organic vapour phase epitaxy (MOVPE) reactors. A combination of low temperature photoluminescence spectroscopy, X-Ray diffractometry, and transmission electron microscopy attest the quality of the new material. We end with a suggestion for the next steps to exceed technological readiness levels of 8, and use monolithic RTD emitters as components in new systems.
Analysing Students’ Scratch Programs and Addressing Issues using Elementary Patterns

In this Work in Progress paper in the Research Category we report on existing concerns about Scratch programming, and introduce patterns as a possible solution. Scratch is a popular language for introducing students to programming, but there is a concern that the students might not be exposed to all the key elements of programming when the development environment tempts them to explore elements such as the range of sprites available. We propose the use of programming patterns as a measure of the sophistication of student work. To understand the importance of patterns we report on our initial work that analyzes a large number of projects from the public Scratch repository to evaluate how extensively the basic patterns appear in student work. This can help inform the improvement of teaching methods to include use of broader range of patterns.