bluuebunny/crossref_metadata_2025_split huggingface dataset:
Playing the piano with a robotic third thumb: assessing constraints of human augmentation
Authors: Shafti Ali , Haar Shlomi , Mio Renato , Guilleminot Pierre , Faisal A. Aldo 
Published: November 2021

AbstractContemporary robotics gives us mechatronic capabilities for augmenting human bodies with extra limbs. However, how our motor control capabilities pose limits on such augmentation is an open question. We developed a Supernumerary Robotic 3rd Thumbs (SR3T) with two degrees-of-freedom controlled by the user’s body to endow them with an extra contralateral thumb on the hand. We demonstrate that a pianist can learn to play the piano with 11 fingers within an hour. We then evaluate 6 naïve and 6 experienced piano players in their prior motor coordination and their capability in piano playing with the robotic augmentation. We show that individuals’ augmented performance with the SR3T could be explained by our new custom motor coordination assessment, the Human Augmentation Motor Coordination Assessment (HAMCA) performed pre-augmentation. Our work demonstrates how supernumerary robotics can augment humans in skilled tasks and that individual differences in their augmentation capability are explainable by their individual motor coordination abilities.
Predictive simulation of post-stroke gait with functional electrical stimulation
Authors: Santos Gilmar F. , Jakubowitz Eike , Pronost Nicolas , Bonis Thomas , Hurschler Christof 
Published: November 2021

AbstractPost-stroke patients present various gait abnormalities such as drop foot, stiff-knee gait (SKG), and knee hyperextension. Functional electrical stimulation (FES) improves drop foot gait although the mechanistic basis for this effect is not well understood. To answer this question, we evaluated the gait of a post-stroke patient walking with and without FES by inverse dynamics analysis and compared the results to an optimal control framework. The effect of FES and cause-effect relationship of changes in knee and ankle muscle strength were investigated; personalized muscle–tendon parameters allowed the prediction of pathologic gait. We also predicted healthy gait patterns at different speeds to simulate the subject walking without impairment. The passive moment of the knee played an important role in the estimation of muscle force with knee hyperextension, which was decreased during FES and knee extensor strengthening. Weakening the knee extensors and strengthening the flexors improved SKG. During FES, weak ankle plantarflexors and strong ankle dorsiflexors resulted in increased ankle dorsiflexion, which reduced drop foot. FES also improved gait speed and reduced circumduction. These findings provide insight into compensatory strategies adopted by post-stroke patients that can guide the design of individualized rehabilitation and treatment programs.
Construction and application of a high precision 3D simulation model for geomechanics of the complex coal seam
Authors: Zhao Lijuan , Zhang Meichen , Jin Xin 
Published: November 2021

AbstractThe high-precision 3D simulation model for geomechanics of a complex coal seam is the necessary premise for the research on intelligent shearer and unmanned mining. However, at present, a simulation model for geomechanics of a complex coal seam generally has the problems of simplifying complex geological structures and low accuracy for structures. In order to meet the needs of a coal seam simulation model in the mining process of an intelligent shearer, it is necessary to optimize the simplified model of a coal seam. Therefore, based on a 3D simplified simulation model constructed with discrete element technology, the complex coal seam application plug-in was compiled with the help of an Application Program Interface. Moreover, according to the geological characteristics, new attributes were added to the structures to complete the construction of the model of a complex coal seam. Finally, the model was verified with laboratory experiments. The results showed that the high-precision 3D simulation model for geomechanics of a complex coal seam effectively improved the accuracy of the modeling. The real-time transmission and the real-time sharing of multi-source data were realized by considering the 3D simulation model for geomechanics of a complex coal seam as the core. Additionally, the purpose of the real-time sensing of the coal cutting state was achieved in order to lay the foundation for the realization of unmanned mining.
Wireless signal modulation identification method based on RF I/Q data distribution
Authors: Wang Lihui , Chen Zhenjia , Zhang Yonghui 
Published: November 2021

AbstractElectromagnetic spectrum detection is the basis of the next generation wireless communication technology. Wireless signal identification is an important part of electromagnetic spectrum detection and management activities. This paper proposes to extract the distribution features of different modulated signals from the signal I/Q data. A two-dimensional gradient matrix is used to describe the characteristics of the signal classification. The minimum gradient cumulative distance (GCD) estimate between the sample and the model is used as the decision criterion for the signal classification. According to the result of the confusion matrix, the weight of the model is adjusted. Experiments show that the recognition rate of the modulated signal mentioned in this paper can reach 82.75%. The I/Q data sample was extracted under actual engineering conditions involving random noise, and the recognition rate dropped to approximately 79%. Based on the initial model gradient matrix, a reasonable algorithm is set to adjust the weight of the model, which can effectively improve the recognition rate of the modulated signal.
Hsp70-containing extracellular vesicles are capable of activating of adaptive immunity in models of mouse melanoma and colon carcinoma
Authors: Komarova Elena Y. , Suezov Roman V. , Nikotina Alina D. , Aksenov Nikolay D. , Garaeva Luiza A. , Shtam Tatiana A. , Zhakhov Alexander V. , Martynova Marina G. , Bystrova Olga A. , Istomina Maria S. , Ischenko Alexander M. , Margulis Boris A. , Guzhova Irina V. 
Published: October 2021

AbstractThe release of Hsp70 chaperone from tumor cells is found to trigger the full-scale anti-cancer immune response. Such release and the proper immune reaction can be induced by the delivery of recombinant Hsp70 to a tumor and we sought to explore how the endogenous Hsp70 can be transported to extracellular space leading to the burst of anti-cancer activity. Hsp70 transport mechanisms were studied by analyzing its intracellular tracks with Rab proteins as well as by using specific inhibitors of membrane domains. To study Hsp70 forms released from cells we employed the assay consisting of two affinity chromatography methods. Hsp70 content in culture medium and extracellular vesicles (EVs) was measured with the aid of ELISA. The properties and composition of EVs were assessed using nanoparticle tracking analysis and immunoblotting. The activity of immune cells was studied using an assay of cytotoxic lymphocytes, and for in vivo studies we employed methods of affinity separation of lymphocyte fractions. Analyzing B16 melanoma cells treated with recombinant Hsp70 we found that the chaperone triggered extracellular transport of its endogenous analog in soluble and enclosed in EVs forms; both species efficiently penetrated adjacent cells and this secondary transport was corroborated with the strong increase of Natural Killer (NK) cell toxicity towards melanoma. When B16 and CT-26 colon cancer cells before their injection in animals were treated with Hsp70-enriched EVs, a powerful anti-cancer effect was observed as shown by a two-fold reduction in tumor growth rate and elevation of life span. We found that the immunomodulatory effect was due to the enhancement of the CD8-positive response and anti-tumor cytokine accumulation; supporting this there was no delay in CT-26 tumor growth when Hsp70-enriched EVs were grafted in nude mice. Importantly, pre-treatment of B16 cells with Hsp70-bearing EVs resulted in a decline of arginase-1-positive macrophages, showing no generation of tumor-associated macrophages. In conclusion, Hsp70-containing EVs generated by specifically treated cancer cells give a full-scale and effective pattern of anti-tumor immune responses.
Controlling droplet splashing and bouncing by dielectrowetting
Authors: Quetzeri-Santiago M. A. , Castrejón-Pita J. R. , Castrejón-Pita A. A. 
Published: November 2021

AbstractStopping droplets from bouncing or splashing after impacting a surface is fundamental in preventing cross-contamination, and the spreading of germs and harmful substances. Here we demonstrate that dielectrowetting can be applied to actively control the dynamics of droplet impact. Moreover, we demonstrate that dielectrowetting can be used to prevent droplet bouncing and suppress splashing. In our experiments, the dielectrowetting effect is produced on a flat substrate by two thin interdigitated electrodes connected to an alternating current potential. Our findings show that the strength of the electric potential can affect the dynamic contact angle and regulate the spreading, splashing and receding dynamics at the right time-scales.
Evaluation of cochlear implant electrode scalar position by 3 Tesla magnet resonance imaging
Authors: Riemann C. , Scholtz L. U. , Gehl H. B. , Schürmann M. , Sudhoff H. , Todt I. 
Published: October 2021

AbstractThe estimation of scalar electrode position is a central point of quality control during the cochlear implant procedure. Ionic radiation is a disadvantage of commonly used radiologic estimation of electrode position. Recent developments in the field of cochlear implant magnets, implant receiver magnet position, and MRI sequence usage allow the postoperative evaluation of inner ear changes after cochlear implantation. The aim of the present study was to evaluate the position of lateral wall and modiolar cochlear implant electrodes using 3 T MRI scanning. In a prospective study, we evaluated 20 patients (10× Med-El Flex 28; 5× HFMS AB and 5× SlimJ AB) with a 3 T MRI and a T2 2D Drive MS sequence (voxel size: 0.3 × 0.3 × 0.9 mm) for the estimation of the intracochlear position of the cochlear implant electrode. In all cases, MRI allowed a determination of the electrode position in relation to the basilar membrane. This observation made the estimation of 19 scala tympani electrode positions and a single case of electrode translocation possible. 3 T MRI scanning allows the estimation of lateral wall and modiolar electrode intracochlear scalar positions.
Biomimetic cellulose-based superabsorbent hydrogels for treating obesity
Authors: Madaghiele Marta , Demitri Christian , Surano Ivo , Silvestri Alessandra , Vitale Milena , Panteca Eliana , Zohar Yishai , Rescigno Maria , Sannino Alessandro 
Published: November 2021

AbstractIn the treatment of obesity, nutritional and behavioral modifications are difficult to implement and maintain. Since vegetable consumption is a fundamental part of many dietary interventions and daily nutrient requirements, we developed a novel cellulose-based superabsorbent hydrogel (CB-SAH) platform, inspired by the composition and mechanical properties of raw vegetables, as a mechanobiological therapy. The CB-SAHs properties were studied in a simulated gastrointestinal environment, while their impact on gut tissue was investigated by an ex vivo organ culture (EVOC) model. Functional fibers and raw vegetables were used as reference. CB-SAHs demonstrated orders of magnitude higher elasticity in comparison to the tested functional fibers, however performed similar to the tested raw vegetables. Notably, the biomimetic CB-SAHs with elasticity levels similar to raw vegetables showed benefits in preserving and regulating the gut tissue in the EVOC model. Non-systemic oral mechanotherapeutics based on this technology were advanced through clinical studies, with a first product cleared as an aid for weight management in the US and Europe.
Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90
Authors: Schmauder Lukas , Absmeier Eva , Bepperling Alexander , Barkovits Katalin , Marcus Katrin , Richter Klaus 
Published: November 2021

AbstractThe molecular chaperones Hsc70 and Hsp90 are required for proteostasis control and specific folding of client proteins in eukaryotic and prokaryotic organisms. Especially in eukaryotes these ATP-driven molecular chaperones are interacting with cofactors that specify the client spectrum and coordinate the ATPase cycles. Here we find that a Hsc70-cofactor of the Hsp40 family from nematodes, DNJ-13, directly interacts with the kinase-specific Hsp90-cofactor CDC-37. The interaction is specific for DNJ-13, while DNJ-12 another DnaJ-like protein of C. elegans, does not bind to CDC-37 in a similar manner. Analytical ultracentrifugation is employed to show that one CDC-37 molecule binds to a dimeric DNJ-13 protein with low micromolar affinity. We perform cross-linking studies with mass spectrometry to identify the interaction site and obtain specific cross-links connecting the N-terminal J-domain of DNJ-13 with the N-terminal domain of CDC-37. Further AUC experiments reveal that both, the N-terminal part of CDC-37 and the C-terminal domain of CDC-37, are required for efficient interaction. Furthermore, the presence of DNJ-13 strengthens the complex formation between CDC-37 and HSP-90 and modulates the nucleotide-dependent effects. These findings on the interaction between Hsp40 proteins and Hsp90-cofactors provide evidence for a more intricate interaction between the two chaperone systems during client processing.
Possible interplay between estrogen and the BAFF may modify thyroid activity in Graves’ disease
Authors: Cheng Chao-Wen , Fang Wen-Fang , Tang Kam-Tsun , Lin Jiunn-Diann 
Published: November 2021

AbstractA link between sex hormones and B-cell activating factor (BAFF), a crucial immunoregulator of autoimmune thyroid disease (AITD), may exist. The study aimed to elucidate the role of estrogen (E2) in regulating BAFF in Graves' disease (GD). In clinical samples, serum BAFF levels were higher in women than in men in both the GD and control groups. serum BAFF levels were associated with thyroid-stimulating hormone receptor antibody levels and thyroid function only in women and not in men. BAFF transcripts in peripheral blood mononuclear cells were higher in women with GD than those in the control group. Among GD patients with the AA genotype of rs2893321, women had higher BAFF transcripts and protein levels than men. In the progression of a spontaneous autoimmune thyroiditis (SAT) murine model, NOD.H-2h4, serum free thyroxine and BAFF levels were higher in female than in male mice. Moreover, exogenous E2 treatment increased serum BAFF levels in male SAT mice. Meanwhile, female SAT mice exhibited higher thyroid BAFF transcripts levels than either the E2-treated or untreated male SAT mouse groups. Our results showed that E2 might be implicated in modulating BAFF expression, and support a possible mechanism for the higher incidence of AITD in women.
A cryo-TSEM with temperature cycling capability allows deep sublimation of ice to uncover fine structures in thick cells
Authors: Usukura Jiro , Narita Akihiro , Matsumoto Tomoharu , Usukura Eiji , Sunaoshi Takeshi , Watanabe Syunya , Tamba Yusuke , Nagakubo Yasuhira , Mizuo Takashi , Azuma Junzo , Osumi Masako , Nimura Kazutaka , Tamochi Ryuichiro , Ose Yoichi 
Published: November 2021

AbstractThe scanning electron microscope (SEM) has been reassembled into a new type of cryo-electron microscope (cryo-TSEM) by installing a new cryo-transfer holder and anti-contamination trap, which allowed simultaneous acquisition of both transmission images (STEM images) and surface images (SEM images) in the frozen state. The ultimate temperatures of the holder and the trap reached − 190 °C and − 210 °C, respectively, by applying a liquid nitrogen slush. The STEM images at 30 kV were comparable to, or superior to, the images acquired with conventional transmission electron microscope (100 kV TEM) in contrast and sharpness. The unroofing method was used to observe membrane cytoskeletons instead of the frozen section and the FIB methods. Deep sublimation of ice surrounding unroofed cells by regulating temperature enabled to emerge intracellular fine structures in thick frozen cells. Hence, fine structures in the vicinity of the cell membrane such as the cytoskeleton, polyribosome chains and endoplasmic reticulum (ER) became visible. The ER was distributed as a wide, flat structure beneath the cell membrane, forming a large spatial network with tubular ER.
Treatment of Pauwels type III femoral neck fracture with medial femoral neck support screw: a biomechanical and clinical study
Authors: Gao Zhichao , Wang Mei , Shen Baojie , Chu Xiaodong , Ruan Di 
Published: November 2021

AbstractA femoral neck fracture is currently one of the most common types of fracture in clinical practice. The incidence continues to increase due to traffic accidents, trauma, and osteoporosis. This research includes a biomechanical study and a clinical retrospective study. In the biomechanical studies, three groups’ effects (Control Group: 3CCS, DHS group, and study Group: 3CCS + mFNSS group) were compared by vertical compression tests, torsion tests, and fatigue tests. All the data were collected and analyzed. We subsequently performed a retrospective analysis of 131 patients with femoral neck fractures. The operative time, intraoperative blood loss, quality of postoperative fracture reduction, and follow-up observation of fracture healing, screw retreatment rates and fixation failure rates, as well as femoral head necrosis rates and hip function in two groups with 3CCS and 3CCS + mFNSS were compared. By the biomechanical study, we found that 3CCS + Mfnss group were biomechanically superior to 3CCS group and superior to the DHS group in terms of resistance to torsion. However, it was less effective than the DHS group in compressive strength and fatigue resistance. In terms of clinical application, 3CCS + mFNSS group was found to have lower screw retreatment rates and femoral head necrosis rates, and to have better fracture healing rates than group with 3CCS, indicating that medial support screws can effectively resist the vertical shear forces of fracture ends and promote the stability and healing of fracture ends, as well as to reduce the incidence of postoperative complications.
Roles of metal ions in the selective inhibition of oncogenic variants of isocitrate dehydrogenase 1
Authors: Liu Shuang , Abboud Martine I. , John Tobias , Mikhailov Victor , Hvinden Ingvild , Walsby-Tickle John , Liu Xiao , Pettinati Ilaria , Cadoux-Hudson Tom , McCullagh James S. O. , Schofield Christopher J. 
Published: November 2021

AbstractCancer linked isocitrate dehydrogenase (IDH) 1 variants, notably R132H IDH1, manifest a ‘gain-of-function’ to reduce 2-oxoglutarate to 2-hydroxyglutarate. High-throughput screens have enabled clinically useful R132H IDH1 inhibitors, mostly allosteric binders at the dimer interface. We report investigations on roles of divalent metal ions in IDH substrate and inhibitor binding that rationalise this observation. Mg2+/Mn2+ ions enhance substrate binding to wt IDH1 and R132H IDH1, but with the former manifesting lower Mg2+/Mn2+KMs. The isocitrate-Mg2+ complex is the preferred wt IDH1 substrate; with R132H IDH1, separate and weaker binding of 2-oxoglutarate and Mg2+ is preferred. Binding of R132H IDH1 inhibitors at the dimer interface weakens binding of active site Mg2+ complexes; their potency is affected by the Mg2+ concentration. Inhibitor selectivity for R132H IDH1 over wt IDH1 substantially arises from different stabilities of wt and R132H IDH1 substrate-Mg2+ complexes. The results reveal the importance of substrate-metal ion complexes in wt and R132H IDH1 catalysis and the basis for selective R132H IDH1 inhibition. Further studies on roles of metal ion complexes in TCA cycle and related metabolism, including from an evolutionary perspective, are of interest.
EGFR Regulates the Hippo pathway by promoting the tyrosine phosphorylation of MOB1
Authors: Ando Toshinori , Arang Nadia , Wang Zhiyong , Costea Daniela Elena , Feng Xiaodong , Goto Yusuke , Izumi Hiroki , Gilardi Mara , Ando Kazuyo , Gutkind J. Silvio 
Published: November 2021

AbstractThe Hippo pathway is frequently dysregulated in cancer, leading to the unrestrained activity of its downstream targets, YAP/TAZ, and aberrant tumor growth. However, the precise mechanisms leading to YAP/TAZ activation in most cancers is still poorly understood. Analysis of large tissue collections revealed YAP activation in most head and neck squamous cell carcinoma (HNSCC), but only 29.8% of HNSCC cases present genetic alterations in the FAT1 tumor suppressor gene that may underlie persistent YAP signaling. EGFR is overexpressed in HNSCC and many other cancers, but whether EGFR controls YAP activation is still poorly understood. Here, we discover that EGFR activates YAP/TAZ in HNSCC cells, but independently of its typical signaling targets, including PI3K. Mechanistically, we find that EGFR promotes the phosphorylation of MOB1, a core Hippo pathway component, and the inactivation of LATS1/2 independently of MST1/2. Transcriptomic analysis reveals that erlotinib, a clinical EGFR inhibitor, inactivates YAP/TAZ. Remarkably, loss of LATS1/2, resulting in aberrant YAP/TAZ activity, confers erlotinib resistance on HNSCC and lung cancer cells. Our findings suggest that EGFR-YAP/TAZ signaling plays a growth-promoting role in cancers harboring EGFR alterations, and that inhibition of YAP/TAZ in combination with EGFR might be beneficial to prevent treatment resistance and cancer recurrence.
Antisense oligonucleotide activity in tumour cells is influenced by intracellular LBPA distribution and extracellular vesicle recycling
Authors: Kapustin Alexander N. , Davey Paul , Longmire David , Matthews Carl , Linnane Emily , Rustogi Nitin , Stavrou Maria , Devine Paul W. A. , Bond Nicholas J. , Hanson Lyndsey , Sonzini Silvia , Revenko Alexey , MacLeod A. Robert , Ross Sarah , Chiarparin Elisabetta , Puri Sanyogitta 
Published: November 2021

AbstractNext generation modified antisense oligonucleotides (ASOs) are commercially approved new therapeutic modalities, yet poor productive uptake and endosomal entrapment in tumour cells limit their broad application. Here we compare intracellular traffic of anti KRAS antisense oligonucleotide (AZD4785) in tumour cell lines PC9 and LK2, with good and poor productive uptake, respectively. We find that the majority of AZD4785 is rapidly delivered to CD63+late endosomes (LE) in both cell lines. Importantly, lysobisphosphatidic acid (LBPA) that triggers ASO LE escape is presented in CD63+LE in PC9 but not in LK2 cells. Moreover, both cell lines recycle AZD4785 in extracellular vesicles (EVs); however, AZD4785 quantification by advanced mass spectrometry and proteomic analysis reveals that LK2 recycles more AZD4785 and RNA-binding proteins. Finally, stimulating LBPA intracellular production or blocking EV recycling enhances AZD4785 activity in LK2 but not in PC9 cells thus offering a possible strategy to enhance ASO potency in tumour cells with poor productive uptake of ASOs.