The Design and Ground Test Verification of an Energy-Efficient Wireless System for the Fatigue Monitoring of Wind Turbine Blades Based on Bistable Piezoelectric Energy Harvesting.

A wireless monitoring system based on piezoelectric energy harvesting (PEH) is presented to provide fatigue data of wind turbine blades in operation. The system comprises three subsystems, each respectively providing the following functions: (i) the conversion of mechanical to electric energy by exploiting the bistable vibration of a composite beam with piezoelectric patches in post-buckling, (ii) harvesting the converted energy by means of a modified, commercial, off-the-shelf (COTS) circuit to feed a LiPo battery and (iii) the battery-powered acquisition and wireless transmission of sensory signals to the cloud to be elaborated upon by the end-user. The system was verified with ground tests under representative operation conditions, which demonstrated the fulfillment of the design requirements. The measurements indicated that the system provided 23% of the required power for fully autonomous operation when subjected to white noise base excitation of 1 g acceleration in the range of 1-20 Hz.

Management of neurological complications related to aneurysmal subarachnoid hemorrhage: A comparison of the bedside therapeutic algorithms.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is of the most serious emergencies in neurosurgical practice and continues to be associated with high morbidity and mortality. Beyond securing the ruptured aneurysm to prevent a rebleed, physicians continue to be concerned about potential complications such as cerebral vasospasm-delayed cerebral ischemia (DCI), an area where management remains highly variable. This study aimed at reviewing the most recent literature and assessing any up-to-date schemes for treating the most common aSAH neurological complications in adults that can be applied in daily clinical practice towards optimising outcomes. METHODS: A systematic review was performed according to PRISMA guidelines on the management of aSAH neurological complications in adults. The literature surveyed was between 2016 and 2022 inclusive, using the Pubmed search engine. Comparisons between the methods suggested by existing therapeutic algorithms were discussed. RESULTS: Six stepwise algorithms assisting the decision-making for treating cerebral vasospasm-DCI were recognised and compared. No algorithm was found for the management of any other neurological complications of aSAH. Despite differences in the algorithms, induced hypertension and endovascular therapy were common treatments in all approaches. Controversy in the therapeutic process of these complications surrounds not only the variability of methods but also their optimal application towards clinical outcome optimisation. CONCLUSIONS: A universal approach to managing aSAH complications is lacking. Despite advances in the techniques to secure a ruptured aneurysm, there persist a high rate of neurological deficit and mortality, and several unanswered questions. More research is required towards stratification of current treatment algorithms as per the quality of their evidence.

A Generalized Model for Compliant Passive Bipedal Walking: Sensitivity Analysis and Implications on Bionic Leg Design.

The passive behavior of a compliant biped walking model, subject to variations in its design, is investigated. A biped gait model is developed that allows for studying the effects of leg impedance, geometry, foot curvature, and inertial properties on the stable gait performed passively. A set of nondimensional parameters has been produced that fully defines the compass gait behavior, eliminating the dependence of our results on scale. Models emerging from parameter combinations were tested on their ability to perform stable passive walking on slope, and the characteristics of the gait performed in each case were recorded. Investigation of parameter ranges allowed us to draw relationships between various gait characteristics and specific, nondimensional parameter selections. By mapping the changes in system behavior under simple design variations, this work facilitates the selection of design parameters at an early stage of designing bionic walking equipment, including prostheses and exoskeletons.

Assessment of Impact Energy Harvesting in Composite Beams with Piezoelectric Transducers.

Piezoelectric energy harvesting (PEH) is studied in the case of a low-velocity impact of a rigid mass on a composite beam. A methodology is outlined, encompassing modelling of the open-circuit impact response in a finite element (FE) package, formulation of a lumped parameter (LP) model for the piezoelectric transducer connected with the harvesting circuit, and experimental verification of the impact using a custom portable configuration with impactor motion control. The subcircuit capacitor charging effect, the impactor mass and velocity on the harvesting subcircuit response, and the obtained output power are quantified. The results indicate that the current methodology can be used as a design tool for the structure and the harvesting circuit to achieve power output from composite beams with piezoelectric patches under impact conditions.

Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation.

ATF4 is a pro-oncogenic transcription factor whose translation is activated by eIF2 phosphorylation through delayed re-initiation involving two uORFs in the mRNA leader. However, in yeast, the effect of eIF2 phosphorylation can be mimicked by eIF5 overexpression, which turns eIF5 into translational inhibitor, thereby promoting translation of GCN4, the yeast ATF4 equivalent. Furthermore, regulatory protein termed eIF5-mimic protein (5MP) can bind eIF2 and inhibit general translation. Here, we show that 5MP1 overexpression in human cells leads to strong formation of 5MP1:eIF2 complex, nearly comparable to that of eIF5:eIF2 complex produced by eIF5 overexpression. Overexpression of eIF5, 5MP1 and 5MP2, the second human paralog, promotes ATF4 expression in certain types of human cells including fibrosarcoma. 5MP overexpression also induces ATF4 expression in Drosophila The knockdown of 5MP1 in fibrosarcoma attenuates ATF4 expression and its tumor formation on nude mice. Since 5MP2 is overproduced in salivary mucoepidermoid carcinoma, we propose that overexpression of eIF5 and 5MP induces translation of ATF4 and potentially other genes with uORFs in their mRNA leaders through delayed re-initiation, thereby enhancing the survival of normal and cancer cells under stress conditions.

Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1.

The eIF4E-binding protein (4E-BP) is a phosphorylation-dependent regulator of protein synthesis. The nonphosphorylated or minimally phosphorylated form binds translation initiation factor 4E (eIF4E), preventing binding of eIF4G and the recruitment of the small ribosomal subunit. Signaling events stimulate serial phosphorylation of 4E-BP, primarily by mammalian target of rapamycin complex 1 (mTORC1) at residues T37/T46, followed by T70 and S65. Hyperphosphorylated 4E-BP dissociates from eIF4E, allowing eIF4E to interact with eIF4G and translation initiation to resume. Because overexpression of eIF4E is linked to cellular transformation, 4E-BP is a tumor suppressor, and up-regulation of its activity is a goal of interest for cancer therapy. A recently discovered small molecule, eIF4E/eIF4G interaction inhibitor 1 (4EGI-1), disrupts the eIF4E/eIF4G interaction and promotes binding of 4E-BP1 to eIF4E. Structures of 14- to 16-residue 4E-BP fragments bound to eIF4E contain the eIF4E consensus binding motif, (54)YXXXXLΦ(60) (motif 1) but lack known phosphorylation sites. We report here a 2.1-Å crystal structure of mouse eIF4E in complex with m(7)GTP and with a fragment of human 4E-BP1, extended C-terminally from the consensus-binding motif (4E-BP150-84). The extension, which includes a proline-turn-helix segment (motif 2) followed by a loop of irregular structure, reveals the location of two phosphorylation sites (S65 and T70). Our major finding is that the C-terminal extension (motif 3) is critical to 4E-BP1-mediated cell cycle arrest and that it partially overlaps with the binding site of 4EGI-1. The binding of 4E-BP1 and 4EGI-1 to eIF4E is therefore not mutually exclusive, and both ligands contribute to shift the equilibrium toward the inhibition of translation initiation.

Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G.

The interaction of the eukaryotic translation initiation factor eIF4E with the initiation factor eIF4G recruits the 40S ribosomal particle to the 5' end of mRNAs, facilitates scanning to the AUG start codon, and is crucial for eukaryotic translation of nearly all genes. Efficient recruitment of the 40S particle is particularly important for translation of mRNAs encoding oncoproteins and growth-promoting factors, which often harbor complex 5' UTRs and require efficient initiation. Thus, inhibiting the eIF4E/eIF4G interaction has emerged as a previously unpursued route for developing anticancer agents. Indeed, we discovered small-molecule inhibitors of this eIF4E/eIF4G interaction (4EGIs) that inhibit translation initiation both in vitro and in vivo and were used successfully in numerous cancer-biology and neurobiology studies. However, their detailed molecular mechanism of action has remained elusive. Here, we show that the eIF4E/eIF4G inhibitor 4EGI-1 acts allosterically by binding to a site on eIF4E distant from the eIF4G binding epitope. Data from NMR mapping and high-resolution crystal structures are congruent with this mechanism, where 4EGI-1 attaches to a hydrophobic pocket of eIF4E between ß-sheet2 (L60-T68) and α-helix1 (E69-N77), causing localized conformational changes mainly in the H78-L85 region. It acts by unfolding a short 310-helix (S82-L85) while extending α-helix1 by one turn (H78-S82). This unusual helix rearrangement has not been seen in any previous eIF4E structure and reveals elements of an allosteric inhibition mechanism leading to the dislocation of eIF4G from eIF4E.

Essential role of eIF5-mimic protein in animal development is linked to control of ATF4 expression.

Translational control of transcription factor ATF4 through paired upstream ORFs (uORFs) plays an important role in eukaryotic gene regulation. While it is typically induced by phosphorylation of eIF2α, ATF4 translation can be also induced by expression of a translational inhibitor protein, eIF5-mimic protein 1 (5MP1, also known as BZW2) in mammals. Here we show that the 5MP gene is maintained in eukaryotes under strong purifying selection, but is uniquely missing in two major phyla, nematoda and ascomycota. The common function of 5MP from protozoa, plants, fungi and insects is to control translation by inhibiting eIF2. The affinity of human 5MP1 to eIF2ß was measured as being equivalent to the published value of human eIF5 to eIF2ß, in agreement with effective competition of 5MP with eIF5 for the main substrate, eIF2. In the red flour beetle, Tribolium castaneum, RNA interference studies indicate that 5MP facilitates expression of GADD34, a downstream target of ATF4. Furthermore, both 5MP and ATF4 are essential for larval development. Finally, 5MP and the paired uORFs allowing ATF4 control are conserved in the entire metazoa except nematoda. Based on these findings, we discuss the phylogenetic and functional linkage between ATF4 regulation and 5MP expression in this group of eukaryotes.

The Role of Dynamics and Allostery in the Inhibition of the eIF4E/eIF4G Translation Initiation Factor Complex.

Lack of regulation of the interaction between the eIF4E/eIF4G subunits of the translation initiation factor complex eIF4F is a hallmark of cancer. The inhibitor 4EGI-1 binds to eIF4E, thereby preventing association with eIF4G through an allosteric mechanism. NMR spectroscopy and MD simulations were used to obtain a mechanistic description of the role of correlated dynamics in this allosteric regulation. We show that binding of 4EGI-1 perturbs native correlated motions and increases correlated fluctuations in part of the eIF4G binding site.

Hypoxia-inducible factor-1α (HIF-1α) promotes cap-dependent translation of selective mRNAs through up-regulating initiation factor eIF4E1 in breast cancer cells under hypoxia conditions.

Hypoxia promotes tumor evolution and metastasis, and hypoxia-inducible factor-1α (HIF-1α) is a key regulator of hypoxia-related cellular processes in cancer. The eIF4E translation initiation factors, eIF4E1, eIF4E2, and eIF4E3, are essential for translation initiation. However, whether and how HIF-1α affects cap-dependent translation through eIF4Es in hypoxic cancer cells has been unknown. Here, we report that HIF-1α promoted cap-dependent translation of selective mRNAs through up-regulation of eIF4E1 in hypoxic breast cancer cells. Hypoxia-promoted breast cancer tumorsphere growth was HIF-1α-dependent. We found that eIF4E1, not eIF4E2 or eIF4E3, is the dominant eIF4E family member in breast cancer cells under both normoxia and hypoxia conditions. eIF4E3 expression was largely sequestered in breast cancer cells at normoxia and hypoxia. Hypoxia up-regulated the expression of eIF4E1 and eIF4E2, but only eIF4E1 expression was HIF-1α-dependent. In hypoxic cancer cells, HIF-1α-up-regulated eIF4E1 enhanced cap-dependent translation of a subset of mRNAs encoding proteins important for breast cancer cell mammosphere growth. In searching for correlations, we discovered that human eIF4E1 promoter harbors multiple potential hypoxia response elements. Furthermore, using chromatin immunoprecipitation (ChIP) and luciferase and point mutation assays, we found that HIF-1α utilized hypoxia response elements in the human eIF4E1 proximal promoter region to activate eIF4E1 expression. Our study suggests that HIF-1α promotes cap-dependent translation of selective mRNAs through up-regulating eIF4E1, which contributes to tumorsphere growth of breast cancer cells at hypoxia. The data shown provide new insights into protein synthesis mechanisms in cancer cells at low oxygen levels.

Solution structure and biophysical properties of MqsA, a Zn-containing antitoxin from Escherichia coli.

The gene ygiT (mqsA) of Escherichia coli encodes MqsA, the antitoxin of the motility quorum sensing regulator (MqsR). Both proteins are considered to form a DNA binding complex and to be involved in the formation of biofilms and persisters. We have determined the three-dimensional solution structure of MqsA by high-resolution NMR. The protein comprises a well-defined N-terminal domain with a Zn finger motif usually found in eukaryotes, and a defined C-terminal domain with a typical prokaryotic DNA binding helix-turn-helix motif. The two well-defined domains of MqsA have almost identical structure in solution and in the two published crystal structures of dimeric MqsA bound to either MqsR or DNA. However, the connection of the two domains with a flexible linker yields a large variety of possible conformations in solution, which is not reflected in the crystal structures. MqsA binds Zn with all four cysteines, a stoichiometry of 1:1 and a femtomolar affinity (K(a)≥ 10¹7M⁻¹ at 23°C, pH 7.0).

Radiation-induced meningiomas (RIM) in adults: A single-centre retrospective experience.

Introduction: Radiotherapy of central nervous system (CNS) is treatment against many paediatric cancers, even if it is a well-recognized risk factor for meningioma formation. An increased risk of developing secondary brain tumors like radiation-induced meningiomas (RIM) is related to irradiated patients. Research question: This retrospective study aims to present RIM cases treated in a single tertiary-hospital in Greece and compare the results with international literature and cases of sporadic meningiomas. Materials and methods: A single-centre retrospective study of all patients diagnosed between January 2012 and September 2022 with RIM after having been irradiated in CNS for paediatric cancer was undertaken through hospital's electronic record and clinical notes, identifying baseline demographics and latency period. Results: Thirteen patients were identified with RIM diagnosis after receiving irradiation for Acute Lymphoblastic Leukaemia (69.2%), Premature Neuro-Ectodermal Tumour (23.1%), and Astrocytoma (7.7%). Median age at irradiation was 5 years old and 32 years old at RIM's presentation. The latent period from irradiation to meningioma diagnosis was 26.23 â€‹± â€‹5.96 years. After surgical excision, histopathologic results showed grade I meningiomas in 12 out of thirteen cases, while only one atypical meningioma was diagnosed. Conclusion: Patients who underwent CNS-radiotherapy in childhood for any condition have an increased risk of developing secondary brain tumors such as radiation-induced meningiomas. RIMs resemble sporadic meningiomas in symptomatology, location, treatment, and histologic grade. However, long-term follow-up and regular check-ups are recommended in irradiated patients due to short latency period from irradiation to RIM development, which means younger age patients than those with sporadic meningiomas cases.

Posterior spinal decompression in adults with spinal cord injury without traumatic compromise of the spinal canal: what is the data?

Background: Spinal cord injury (SCI) can be caused by a variety of factors and its severity can range from a mild concussion to a complete severing of the spinal cord. Τreatment depends on the type and severity of injury, the patient's age and overall health. Reduction of dislocated or fractured vertebrae via closed manipulation or surgical procedures, fixation and removal of bony fragments and debris that compromise the spinal canal are indicated for decompression of the spinal cord and stabilization of the spine. However, when there is no obvious traumatic obstruction of spinal canal, the question arises as to whether laminectomy is needed to be performed to improve neurological outcome. Methods: A literature review covering all indexed studies published between 2013 and 2023 was performed using keywords to identify the patient group of interest (spinal cord injury, SCI, spinal cord trauma, cervical, thoracic, lumbar, thoracolumbar),central cord syndrome (CCS) and the interventions (laminectomy, laminoplasty, decompression, duroplasty). Results: This review includes6 observational studies investigating the outcome of posterior spinal decompression in patients suffering from spinal cord injury without traumatic spinal cord stenosis. Most patients already had degenerative stenosis. From a total of 202, 151 patients (74.7%) improved neurologically by at least one grade at ASIA scale, after being treated with either laminectomy, laminoplasty, duroplasty or a combination of these techniques. Conclusion: Early decompression in SCI patients remains a reasonable practice option and can be performed safely, but no specific evidence supports the use of laminectomy alone. There is emerging evidence that intended durotomy followed by extended meningoplasty may improve the neurological outcome in patients suffering from SCI when meta-traumatic edema is apparent. However, the lack of high-quality evidence and results support the need for further research.

Controversies in the Surgical Treatment of Chronic Subdural Hematoma: A Systematic Scoping Review.

Chronic subdural hematoma (cSDH) is one of the most common neurosurgical entities, especially in the elderly population. Diagnosis is usually established via a head computed tomography, while an increasing number of studies are investigating biomarkers to predict the natural history of cSDH, including progression and recurrence. Surgical evacuation remains the mainstay of treatment in the overwhelming majority of cases. Nevertheless, many controversies are associated with the nuances of surgical treatment. We performed a systematic review of the literature between 2010 and 2022, aiming to identify and address the issues in cSDH surgical management where consensus is lacking. The results show ambiguous data in regard to indication, the timing and type of surgery, the duration of drainage, concomitant membranectomy and the need for embolization of the middle meningeal artery. Other aspects of surgical treatment-such as the use of drainage and its location and number of burr holes-seem to have been adequately clarified: the drainage of hematoma is strongly recommended and the outcome is considered as independent of drainage location or the number of burr holes.

Robotic Manipulation and Capture in Space: A Survey.

Space exploration and exploitation depend on the development of on-orbit robotic capabilities for tasks such as servicing of satellites, removing of orbital debris, or construction and maintenance of orbital assets. Manipulation and capture of objects on-orbit are key enablers for these capabilities. This survey addresses fundamental aspects of manipulation and capture, such as the dynamics of space manipulator systems (SMS), i.e., satellites equipped with manipulators, the contact dynamics between manipulator grippers/payloads and targets, and the methods for identifying properties of SMSs and their targets. Also, it presents recent work of sensing pose and system states, of motion planning for capturing a target, and of feedback control methods for SMS during motion or interaction tasks. Finally, the paper reviews major ground testing testbeds for capture operations, and several notable missions and technologies developed for capture of targets on-orbit.

A biphenyl inhibitor of eIF4E targeting an internal binding site enables the design of cell-permeable PROTAC-degraders.

The eukaryotic translation initiation factor 4E (eIF4E) is the master regulator of cap-dependent protein synthesis. Overexpression of eIF4E is implicated in diseases such as cancer, where dysregulation of oncogenic protein translation is frequently observed. eIF4E has been an attractive target for cancer treatment. Here we report a high-resolution X-ray crystal structure of eIF4E in complex with a novel inhibitor (i4EG-BiP) that targets an internal binding site, in contrast to the previously described inhibitor, 4EGI-1, which binds to the surface. We demonstrate that i4EG-BiP is able to displace the scaffold protein eIF4G and inhibit the proliferation of cancer cells. We provide insights into how i4EG-BiP is able to inhibit cap-dependent translation by increasing the eIF4E-4E-BP1 interaction while diminishing the interaction of eIF4E with eIF4G. Leveraging structural details, we designed proteolysis targeted chimeras (PROTACs) derived from 4EGI-1 and i4EG-BiP and characterized these on biochemical and cellular levels. We were able to design PROTACs capable of binding eIF4E and successfully engaging Cereblon, which targets proteins for proteolysis. However, these initial PROTACs did not successfully stimulate degradation of eIF4E, possibly due to competitive effects from 4E-BP1 binding. Our results highlight challenges of targeted proteasomal degradation of eIF4E that must be addressed by future efforts.

Solution structure of the HsapBK K+ channel voltage-sensor paddle sequence.

Voltage-gated potassium channels open and close in response to changes in the membrane potential. In this study, we have determined the NMR solution structure of the putative S3b-S4 voltage-sensor paddle fragment, the part that moves to mediate voltage gating, of the HsapBK potassium channel in dodecylphosphocholine (DPC) micelles. This paper presents the first structure of the S3b-S4 fragment from a BK channel. Diffusion coefficients as determined from PFG NMR experiments showed that a well-defined complex between the peptide and DPC molecules was formed. The structure reveals a helix-turn-helix motif, which is in agreement with crystal structures of other voltage-gated potassium channels, thus indicating that it is feasible to study the isolated fragment. The paddle motifs generally contain several basic residues, implicated in the gating. The critical Arg residues in this structure all reside on the surface, which is in agreement with crystal structures of K(v) channels. Similarities in the structure of the S3b-S4 fragment in BK and K(v) channels as well as important differences are seen, which may be important for explaining the details in paddle movement within a bilayer.

A Biomechatronic EPP upper-limb prosthesis controller and its performance comparison to other topologies.

Historically, Classic Extended Physiological Proprioception (EPP) as an upper-limb prosthesis control topology has been outperforming functionally all other topologies of the past. A novel Biomechatronic EPP controller has been designed to overcome shortcomings of the classic EPP control topology, and has been hypothesized to be functionally equivalent to the classic EPP topology. Using the dSpace realtime hardware platform and other mechanical and electronic components, the following were developed in the lab: (a) A Biomechatronic EPP controller, (b) a classic EPP controller, (c) an "unconnected" controller and (d) an EMG controller. All four topologies were tested in the lab using the target experiments methodology. Initial results of one subject show that performance of (a) is superior or comparable to (b) and superior to (c) and (d).

A Biomechatronic EPP upper-limb prosthesis teleoperation system implementation using Bluetooth Low Energy.

In this paper a real time, stand-alone wireless Biomechatronic Extended Physiological Proprioception (EPP) teleoperation system was implemented using two Bluetooth Low Energy (BLE) wireless Systems on Chip (SoCs). This system is designed to achieve kinesthetic coupling between the amputee and prosthetic arm without the use of the classic EPP mechanical linkage, but with the use of a wireless implementation of a Master/Slave teleoperation topology. The experimental real-time implementation achieved a high level of transparency with minuscule time delays.