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A anemia falciforme é uma doença hereditária recessiva causada por uma mutação em um único nucleotídeo no gene da beta globina. Esta mutação provoca uma alteração estrutural na qual o ácido glutâmico é substituído por uma valina acarretando na falcização das hemácias quando desoxigenadas. Alguns fármacos com ação hipometilante são capazes de induzir a expressão de gama globina através da inibição da metilação no promotor desse gene. Porém, pouco se sabe a respeito desta regulação e sobre os genes envolvidos neste processo. Visando compreender esta regulação, células CD34+, de indivíduos controle, foram tratadas com 1μM de Decitabina no 9°dia de cultura celular para indução da produção de Hemoglobina Fetal (HbF). Os níveis de expressão dos fatores de transcrição e modificadores da cromatina foram avaliados por meio da plataforma PCR Array (Qiagen™ Germany). Nesse ensaio, foram evidenciados 24 fatores de transcrição diferencialmente expressos, dentre eles, o HNF4α (Hepatocyte Nuclear Factor 4 Alpha) regulado positivamente em 26,1 vezes, HNF1α (Hepatocyte Nuclear Factor 1 Homeobox A) 20,0 vezes e o TCF7L2 (Transcription Factor 7 Like 2) 5,9 vezes, em células tratadas com Decitabina comparadas ao controle. Selecionamos o gene HNF4α como um candidato para silenciamento utilizando a ferramenta CRISPR/Cas9 em células HUDEP-2 (immortalized human erythroid progenitor) por ser o fator de transcriação com maior valor diferencial de expressão entre os listados. O HNF4α é descrito como um fator de transcrição que regula a expressão de vários genes hepáticos, podendo atuar no desenvolvimento do fígado, rim e intestinos e é expresso em tecido hematopoiético. As células HUDEP-2 foram tratadas com Decitabina 50 nM e coletadas após 72 horas. Os níveis de HbF foram mensurados por citometria de fluxo em triplicas biológicas. A porcentagem de células positivas para HbF em HUDEP-2, tratada com Decitabina, foi de 12,27 ± 0,7% n = 3, enquanto nas células controle 1,0 ± 0,06% n = 3, p < 0,0001. Estes resultados corroboram o aumento da expressão observado nas células CD34+. As células HUDEP-2 foram nucleofectedas com Cas9 high fidelity (104 pmol), complexo crRNA: tracrRNA (120 pmol) e 1uM de gRNA HNF4α usando o kit de células humanas CD34+ no dispositivo AMAXA Nucleofector 4D (Lonza). 48 horas após a nucleofecção, as células HUDEP-2 editadas foram submetidas à seleção de clones e expandidas por aproximadamente 28 dias. O DNA genômico dos clones foi sequenciado, e quatro clones -HNF4α-HUDEP-2 foram encontrados com indels no quarto éxon do gene HNF4α. Esses clones foram expandidos em cultura com um controle, e os níveis de HbF foram quantificados com anticorpo anti-HbF por citometria de fluxo. Os níveis de HbF destes quatro clones foram de 8,2 ± 2,4%, o nível do controle foi de 0,9 ± 0,02% p < 0,0258. Os clones editados, embora não homogeneamente, expressaram significativamente mais HbF do que o controle. Nossos resultados sugerem que o HNF4α pode desempenhar um papel importante na ativação do gene da gama globina em células HUDEP-2. Adicionalmente, o aumento na expressão dos genes TCF7L2 e HNF1α são sugestivos de um possível papel na regulação de HbF. Esses dados são importantes, pois indicam novos possíveis alvos para terapia gênica em hemoglobinopatias.

Abstract Background Inflammatory Bowel Disease (IBD) constitutes a huge burden for patients and studies show that IBD patients have difficulties remaining in employment. Because there is no data about the unemployment of IBD patients in Japan. Methods We surveyed a representative sample of 1068 Japanese IBD patients regarding their employment status. Results We found that the labor force participation rate is lower and unemployment higher for patients with IBD compared to the general population. Factors associated with unemployment in the IBD sample are older age, female gender, and the prevalence of depression. Discussion IBD constitutes a high burden for patients in Japan regarding employment outcome.

Abstract The Scibar Cosmic-Ray Telescope (SciCRT) is the most promising detector of the Sierra Negra Cosmic Rays Observatory (SN-CRO). At this location, being a target and a tracker of secondary cosmic rays, the SciCRT offers a high probability of observing solar energetic particles and lower energy galactic cosmic rays (LEGCR); also, it allows the identification of incoming particles by measuring their energy deposition. In this work we present a Geant4-based simulation of the energy deposited by neutrons, $$\gamma $$ γ -rays, protons, electrons and muons in the optimally running SciCRT components. We also calculated the detection efficiency of the SciCRT at its current state. Our simulation results provide new information about the SciCRT detection response that may be used as a basis to estimate and analyze the energy spectra of primary particles.

The diel habitat-use patterns of commercially important fishes in a small marine protected area (MPA) (0.31 km2) containing coral reef and seagrass habitats were examined by passive acoustic telemetry during 2011 and 2012. The occurrence patterns of the target fishes both inside and outside the MPA were also observed. Thirty individuals from 6 species (20.2 to 41.4 cm fork length) were caught, acoustically tagged and released inside the MPA, and 4 to 210 d of tracking data were then obtained from 28 detected fishes. Lutjanus monostigma, Lethrinus atkinsoni, and Lethrinus obsoletus were found to mostly inhabit the coral reef. The remaining 3 species (Lutjanus argentimaculatus, Lethrinus harak, and Siganus guttatus) utilized both coral and seagrass habitats but showed different patterns: Lutjanus argentimaculatus visited seagrass only at night; Lethrinus harak occurred in the coral reef more at night than in the day, showing the opposite pattern in seagrass; and S. guttatus exhibited the converse pattern to L. harak. More than one-third of the tracked individuals moved inside and outside the MPA more than once per day on average during the tracking period. However, 95.4% of detections were recorded by acoustic receivers deployed inside the MPA. Underwater visual surveys revealed that the densities of some target fishes were significantly higher inside than outside the MPA. These findings suggest that the MPA protects the core of fish home ranges.

Degeneration of the lumbar intervertebral discs is irreversible, with no treatment currently available. Building upon experimental studies that demonstrated the importance of the nucleus pulposus (NP) in preserving disc structure, we demonstrated that reinsertion of NP cells slowed further disc degeneration and that direct cell-to-cell contact co-culture with mesenchymal stromal cells (MSCs) significantly upregulated the viability of NP cells in basic and pre-clinical studies in vitro and in vivo using animal models and human cells. Here, we report a 3-year result of a prospective clinical study, aimed to assess the safety and efficacy of activated NP cell transplantation in the degenerate lumbar intervertebral disc. Candidates were 9 patients aged 20-29 years who had Pfirrmann’s grade III disc degeneration at the level adjacent to the level scheduled for posterior lumbar intervertebral fusion. Viable NP cells from the fused disc were co-cultured in direct contact with autologous bone marrow-derived MSCs. One million activated NP cells were transplanted into the degenerated disc adjacent to the fused level at 7 d after the first fusion surgery. No adverse effects were observed during the 3-year follow-up period. Magnetic resonance imaging did not show any detrimental effects to the transplanted discs and revealed a mild improvement in 1 case. No cases reported any low back pain. Our clinical study confirmed the safety of activated NP cell transplantation, and the findings suggest the minimal efficacy of this treatment to slow the further degeneration of human intervertebral discs.

The present study explored the importance of chemical cues for habitat selection by fish (6 species), crustacean (1 species), and cephalopod (1 species) larvae in a 4-channel choice flume at Ishigaki Island, Japan. The larval attraction toward chemical cues from reef patches (seagrass bed patch, live coral patch, dead coral patch, and control water; Expt 1) and microhabitats within a given reef patch (live coral colonies, dead coral colonies, seagrass, and conspecifics; Expt 2) was tested in a 4-channel choice flume. The results in Expt 1 showed that 3 fish species used chemical cues to move significantly towards reef patches: Chromis viridis toward live coral patch water and Lutjanus fulviflamma and L. gibbus toward seagrass bed patch water. In Expt 2, 6 of 8 species (4 fishes, 1 cephalopod, and 1 crustacean) used chemical cues to move significantly toward conspecific water (Apogon properuptus, C. viridis, Dascyllus reticulatus, L. fulviflamma, Octopus cyanea, and Palaemonidae sp.). Overall, these results suggest that marine species can actively select settlement habitats according to olfactory cues (more specially, cues from conspecifics). Moreover, these results highlight the importance of conspecific cues over other types of information (reef patch and microhabitat) for habitat selection. Social aggregation of fish, crustacean, and cephalopod larvae with older conspecifics may be the result of individuals using conspecific ‘guides’ to potentially find beneficial resources (availability of resources and low mortality).

Background: Evaluating multiple biomarkers including human epidermal growth factor receptor 2 (HER2), mismatch repair (MMR) status, programed death-ligand 1 (PD-L1), and claudin 18.2 (CLDN18.2) is essential for selecting appropriate first-line therapy of metastatic gastroesophageal adenocarcinoma (mGEA). However, this can be challenging if tumor tissue amount is limited and may cause delays in the initiation of chemotherapy. Therefore, we assessed the feasibility of multiple biomarkers testing in routine clinical practice. Materials and methods: We reviewed the medical records of treatment-naïve patients with mGEA who underwent prospective multiple biomarkers testing between April 2022 and October 2023 in our institution. Eight biomarker status including HER2, MMR, PD-L1, CLDN18.2, Epstein–Barr virus, fibroblast growth factor receptor 2, epidermal growth factor receptor and mesenchymal epithelial transition expressions were simultaneously examined using biopsy or surgical specimens. Results: A total of 203 patients with mGEA were analyzed. Most patients underwent gastroendoscopy and tumor biopsy shortly after referral to our institution. Biomarkers testing was successfully completed on the first attempt in 198 patients (97.5%). With additional steps including additional biopsy or asking remaining tumor samples from the referring hospital, the biomarker results were eventually available in all cases. The median turnaround time from sample collection to reporting results was 7 days. Consequently, 178 patients (87.7%) could receive first-line treatment after obtaining the biomarker status. Conclusions: Multiple biomarkers testing for patients with mGEA was feasible in clinical practice. Establishment of a testing infrastructure based on the collaboration with multiple departments is essential for implementing biomarker-driven precision treatment.

Magnetostatic modes supported by a ferromagnetic sphere have been known as the Walker modes, each of which possesses an orbital angular momentum as well as a spin angular momentum along a static magnetic field. The Walker modes with non-zero orbital angular momenta exhibit topologically non-trivial spin textures, which we call magnetic quasi-vortices . Photons in optical whispering gallery modes supported by a dielectric sphere possess orbital and spin angular momenta forming optical vortices . Within a ferromagnetic, as well as dielectric, sphere, two forms of vortices interact in the process of Brillouin light scattering. We argue that in the scattering there is a selection rule that dictates the exchange of orbital angular momenta between the vortices. The selection rule is shown to be responsible for the experimentally observed nonreciprocal Brillouin light scattering.

Although intervertebral disc herniation and associated sciatica is a common disease, its molecular pathogenesis is not well understood. Immune responses are thought to be involved. This study provides direct evidence that even non-degenerated nucleus pulposus (NP) cells elicit immune responses. An in vitro colony forming inhibition assay demonstrated the suppressive effects of autologous spleen cells on NP cells and an in vitro cytotoxicity assay showed the positive cytotoxic effects of natural killer (NK) cells and macrophages on NP cells. Non-degenerated rat NP tissues transplanted into wild type rats and immune-deficient mice demonstrated a significantly higher NP cell survival rate in immune-deficient mice. Immunohistochemical staining showed the presence of macrophages and NK cells in the transplanted NP tissues. These results suggest that even non-degenerated autologous NP cells are recognized by macrophages and NK cells, which may have an immunological function in the early phase of disc herniation. These findings contribute to understanding resorption and the inflammatory reaction to disc herniation.

Abstract Recently, integrated geophysical‐geological surveys in the Nankai subduction zone in Japan have revealed that slow earthquakes repeatedly occur beneath the outer wedge of the forearc. During December 2020 to February 2021, clustered slow earthquakes propagated around the frontal thrust of the accretionary wedge. The frontal thrust ramps up from the basal décollement and slips over trench‐filling sediment along the landward edge of the Nankai trough floor. Here, the Paleo‐Zenisu ridge has been subducted beneath the inner‐outer slope border. In addition, ocean floor topography and geologic structure revealed by seismic reflection surveys completed before 2022 document that the basement of the Philippine Sea Plate beneath the frontal thrust has a seamount and a horst‐like basement high. The northern edge of the basement high is located at the ramp‐up position of the frontal thrust. The 2020–2021 clustered slow earthquakes started at the Paleo‐Zenisu ridge and propagated to the topographic highs beneath the deformation front. Considering that the relative plate convergence between the upper Amurian Plate of the Nankai forearc and the subducting Philippine Sea Plate is ∼6.0 cm/year, the basement high at the deformation front has uplifted the frontal crest of the wedge at an average rate of 2.7–5.7 mm/year for several tens to hundred thousand years. These rates are among some of the highest rock uplift rates measured in the world. The slow earthquakes in the off‐Kumano Nankai Trough in 2020–2021 are a snapshot of a “living” Nankai frontal thrust during the megathrust interseismic period.

International treatment guidelines recommend tumor resection for patients with oligometastatic colorectal cancer (CRC). Despite this, recurrence occurs in ∼60% of patients post-surgery, indicating that the role and optimal type of perioperative systemic therapy has not been fully defined. In the COSMOS-oligo trials, comprising two studies, we are evaluating the potential role of circulating tumor DNA (ctDNA) analysis in clinical decision making and exploring adjuvant therapy strategies for patients with resectable metastatic CRC. The COSMOS-CRC-03 study aims to evaluate the prognostic value of post-operative minimal residual disease as detected by ctDNA and to explore the role of ctDNA in detecting disease recurrence. We plan to assess the predictive accuracy of ctDNA results for recurrence using blood collected 28 days post-surgery. We will additionally explore whether regular post-operative ctDNA test can detect recurrence earlier than standard imaging. Post-operative adjuvant therapy will not be administered to ctDNA-negative patients. The complementary AURORA trial is a randomized phase II study designed to test whether post-operative mFOLFOXIRI plus bevacizumab is superior to standard mFOLFOX6 for patients with metastatic CRC when the ctDNA status is positive after curative-intent surgery for patients enrolled in the COSMOS-CRC-03 study. Both studies will only include patients with resectable distant metastases of CRC. We designed these studies to stratify patients based on the results of a ctDNA assay and to determine the optimal treatment for patients at the highest risk for recurrence.

We study the system where a superconducting flux qubit is capacitively coupled to an LC resonator. In three devices with different coupling capacitance, the magnitude of the dispersive shift is enhanced by the third level of the qubit and quantitatively agrees with the theory. We show by numerical calculation that the capacitive coupling plays an essential role for the enhancement in the dispersive shift. We investigate the coherence properties in two of these devices, which are in the strong-dispersive regime, and show that the qubit energy relaxation is currently not limited by the coupling. We also observe the discrete ac-Stark effect, a hallmark of the strong-dispersive regime, in accordance with the theory.

We aimed to (1) compare external training loads obtained in futsal players during pre-season and in-season training weeks to explore how these loads are periodized by the coaching staff; and (2) compare the external training loads using the match day minus approach during the pre-season and in-season periods to determine how the within-microcycle training load varies between these periods. A total of 432 recordings were obtained of twelve national-level male amateur players using IPS devices. These data were collected over four consecutive microcycles from the beginning to the end of the pre-season, as well as during four additional consecutive microcycles at the start of the in-season. The external load variables evaluated were: total distance covered (TD; m), relative distance covered (Drel; m/min), high-speed running (HSR; m > 18.8 km/h), sprint distance (SPR; m > 25.2 km/h), number of intense accelerations (ACC; >2.5 m/s2) and decelerations (DEC; >−2.5 m/s2). Results indicated significant week-by-week variation (p < 0.05) in all external load variables during the pre-season. During the in-season, significant variations (p < 0.05) were observed only in Drel, HSR, and ACC. In both phases, all variables were higher (p < 0.05) two days before the match. In conclusion, it is important to consistently quantify the external loads of futsal players to ensure appropriate variation in loading and tapering within the microcycle, as well as during the pre-season and in-season periods.

The aims of this study were to: (a) determine the differences in external load quantification between arbitrary and individual speed thresholds over the weekly microcycle in professional soccer players, and (b) analyse the association between internal load and different external load quantification strategies (ELQSs). Ten professional outfield players were monitored during training sessions and official matches using 10 Hz GPS devices over a 6-week in-season period. The absolute and relative (“R” before the distance category) distances covered were calculated for the following external load variables: medium-intensity running distance (MIR), highintensity running (HIR), sprint distance (SD), and very high-intensity running (VHIR). Individualized thresholds were determined based on maximal sprinting speed (MSS) and the last speed achieved during the 30–15 Intermittent Fitness Test (V IFT ) of each player. In terms of match-day workload, significant differences (p < 0.05) were observed between arbitrary and individualized strategies (i.e., MSS and V IFT ) for the distance covered in MIR, HIR, SD, VHIR, RHIR, RSD, and RVHIR. The MSS strategy compared to arbitrary thresholds revealed significant differences (p < 0.05) for distance covered in HIR, RHIR, and VHIR during all training sessions. The present results showed that arbitrary thresholds lead to underestimation of external load absolute and relative metrics compared to the MSS strategy throughout the microcycle. The V IFT strategy mainly revealed differences in external load quantification regarding MD compared to arbitrary thresholds. Individualized speed threshold strategies did not achieve better associations with internal load measures in comparison with arbitrary thresholds in professional soccer players.

Cigarette smoke has been recognized as a major risk factor for cardiovascular disease. However, its direct effects on rodent and human cardiomyocytes and its cellular mechanisms are not fully understood. In this study, we examined the direct effects of cigarette smoke extract (CSE) on contractile functions, intracellular Ca2+ dynamics, and mitochondrial function using cultured or freshly isolated rat ventricular myocytes and human induced pluripotent stem cell (iPS)-derived cardiomyocytes. In rat cardiomyocytes, CSE (≥0.1%) resulted in a time- and concentration-dependent cessation of spontaneous beating of cultured cardiomyocytes, eventually leading to cell death, which indicates direct toxicity. In addition, 1% CSE reduced contractile function of freshly isolated ventricular myocytes. Similar contractile dysfunction (declined spontaneous beating rate and contractility) was also observed in human iPS-derived cardiomyocytes. Regarding intracellular Ca2+ dynamics, 1% CSE increased the Ca2+ transient amplitude by greatly increasing systolic Ca2+ levels and slightly increasing diastolic Ca2+ levels. CSE also accelerated the decay of Ca2+ transients, and triggered spike-shaped Ca2+ transients in some cells. These results indicate that CSE causes abnormal Ca2+ dynamics in cardiomyocytes. Furthermore, CSE induced a cascade of mitochondrial dysfunctions, including increased mitochondrial reactive oxygen species, opening of mitochondrial permeability transition pore, reduction of mitochondrial membrane potential, and release of cytochrome c from mitochondria. These results suggest that CSE-induced contractile dysfunction and myocardial cell death is caused by abnormal Ca2+ dynamics and subsequent mitochondrial dysregulation, which would result in reduced bioenergetics and activation of cell death pathways.

Josephson parametric amplifiers (JPA) are promising devices for applications in circuit quantum electrodynamics and for studies on propagating quantum microwaves because of their good noise performance. In this work, we present a systematic characterization of a flux-driven JPA at millikelvin temperatures. In particular, we study in detail its squeezing properties by two different detection techniques. With the homodyne setup, we observe the squeezing of vacuum fluctuations by superposing signal and idler bands. For a quantitative analysis, we apply dual-path cross-correlation techniques to reconstruct the Wigner functions of various squeezed vacuum and thermal states. At 10 dB signal gain, we find 4.9 ± 0.2 dB squeezing below the vacuum. In addition, we discuss the physics behind squeezed coherent microwave fields. Finally, we analyze the JPA noise temperature in the degenerate mode and find a value smaller than the standard quantum limit for phase-insensitive amplifiers.

Background: The programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1)/programmed cell death-ligand 2 (PD-L2) axis is responsible for cancer immune escape, which facilitates disease progression. However, the role of PD-L1 and PD-L2 and tumor-infiltrating lymphocytes (TILs) in metastatic colorectal cancer (mCRC) has not been studied. Materials and methods: We conducted a post-hoc analysis of the Nationwide Cancer Genome Screening Project GI-SCREEN in mCRC. PD-L1 (22C3) and PD-L2 (MEB123.3G2.038) expression in formalin-fixed paraffin-embedded tumor samples was centrally assessed by immunohistochemical assays. TILs were morphologically evaluated using hematoxylin and eosin staining. Clinical information was extracted from the GI-SCREEN database. Inclusion of patients with BRAF V600E mutation was prioritized. Results: Two hundred patients with mCRC (median age 65 years and 116 males) were included in the study. Genomic testing identified RAS mutations in 87 (44%) patients, BRAF V600E mutations in 27 (14%), and microsatellite instability-high status in 8 (4%). Positivity of PD-L1 and PD-L2 was 11% and 47% on tumor cells (TC) and 0% and 64% on immune cells, respectively, and that was associated with the presence of TILs (P = 0.011 for PD-L1, 0.024 for PD-L2). PD-L1+ TC was significantly more frequent in BRAF V600E-mutated tumors (P = 0.03). Even in microsatellite stable tumors, BRAF V600E-mutated tumors were significantly associated with higher expression of PD-L1 on TC than BRAF wild-type (25% versus 8%, P = 0.02). Conclusions: Our study showed a distinct pattern of PD-L1 expression on TC of patients with BRAF V600E-mutated mCRC, which could be a potential therapeutic target for PD-1 blockade.

Abstract Gamma‐ray glows are observational evidence of relativistic electron acceleration due to the electric field in thunderclouds. However, it is yet to be understood whether such relativistic electrons contribute to the initiation of lightning discharges. To tackle this question, we started the citizen science “Thundercloud Project,” where we map radiation measurements of glows from winter thunderclouds along Japan's sea coast area. We developed and deployed 58 compact gamma‐ray monitors at the end of 2021. On 30 December 2021, five monitors simultaneously detected a glow with its radiation distribution horizontally extending for 2 km. The glow terminated coinciding with a lightning flash at 04:08:34 JST, which was recorded by the two radio‐band lightning mapping systems, FALMA and DALMA. The initial discharges during the preliminary breakdown started above the glow, that is, in vicinity of the electron acceleration site. This result provides one example of possible connections between electron acceleration and lightning initiation.

A higher plasma β is desirable for realizing high performance fusion reactor, in fact, one of the three goals of JT-60SA project is to achieve a high- β regime. We investigate key physical processes that regulate the β dependence of turbulent transport in L-mode plasmas by means of both local and global gyrokinetic simulations. From local simulations, we found that the turbulent transport does not decrease as β increases, because the electromagnetic stabilizing effect is canceled out by the increase of the Shafranov shift. This influence of the Shafranov shift is suppressed when the magnetic shear is weak, and thus the electromagnetic stabilization is prominent in weak shear plasmas, suggesting an advantage of weak magnetic shear plasmas for achieving a high- β regime. In high β regime, local gyrokinetic simulations are suffered from the non-saturation of turbulence level. In global simulations, by contrast, the electromagnetic turbulence gets saturated by the entropy advection in the radial direction to avoid the zonal flow erosion due to magnetic fluctuations. This breakthrough enables us to explore turbulent transport at a higher β regime by gyrokinetic simulations.

In a honeycomb-lattice spin-orbit assisted Mott insulator α-RuCl_{3}, ultrafast magnetization is induced by circularly polarized excitation below the Mott gap. Photocarriers play an important role, which are generated by turning down the synergy of the onsite Coulomb interaction and the spin-orbit interaction realizing the insulator state. An ultrafast 6 fs measurement of photocarrier dynamics and a quantum mechanical analysis clarify the mechanism, according to which the magnetization emerges from a coherent charge motion between different t_{2g} orbitals (d_{yz}-d_{xz}-d_{xy}) of Ru^{3+} ions. This ultrafast magnetization is weakened in the antiferromagnetic (AFM) phase, which is opposite to the general tendency that the inverse Faraday effect is larger in AFM compounds than in paramagnetic ones. This temperature dependence indicates that the interorbital charge motion is affected by pseudospin rotational symmetry breaking in the AFM phase.

Research has shown that soccer players regularly execute curved sprints during matches. The purpose of this study was to determine the age-related effects on curve sprint (CS) performance to both sides, asymmetry, and association with linear sprint (LS). Eighty-four soccer players (aged 16.1 ± 1.6 categorized in U15, U17, and U20) were recruited, who performed CS and LS tests. One-way analysis of variance (ANOVA) and effect size (ES) were used to compare CS performance between age categories, and relationships between physical performance measures were calculated using Pearson’s correlation coefficient. The main findings of this study were that: 1) there were significant differences in the “good” side CS among age groups (p < 0.001; ES from moderate to large), but not in the “weak” side CS, 2) curve asymmetry was significantly higher in U20 than U15 (p < 0.05; ES large) and U17 players (p < 0.05; ES moderate), and 3) relationships between CS and LS times decreased with age (from significant and very large [p 0.05]). This study highlights the importance of assessing and training CS in different age categories, an action that becomes less correlated with LS as age increases, with the aim of mitigating the increase in asymmetries as a result of the specialization process, focusing interventions mainly on improving the CS “weak” side.

This systematic review and meta-analysis aimed to analyse the technologies and main training variables used in the literature to monitor flywheel training devices in real time. In addition, as the main research question, we investigated how eccentric overload can be effectively monitored in relation to the training variable, flywheel shaft type device and the moment of inertia selected. The initial search resulted in 11,621 articles that were filtered to twenty-eight and seventeen articles that met the inclusion criteria for the systematic review and meta-analysis, respectively. The main technologies used included force sensors and rotary/linear encoders, mainly to monitor peak or mean force, power or speed. An eccentric overload was not always achieved using flywheel devices. The eccentric overload measurement wasrelated to the main outcome selected. While mean force (p = 0.011, ES = -0.84) and mean power (p < 0.001, ES = -0.30) favoured the concentric phase, peak power (p < 0.001, ES = 0.78) and peak speed (p < 0.001, ES = 0.37) favoured the eccentric phase. In addition, the lower moments of inertia (i.e., from 0.01 to 0.2 kg·m2 ) and a cylindrical shaft type (i.e., vs conical pulley) showed higher possibilities to achieve eccentric overload. A wide variety of technologies can be used to monitor flywheel devices, but to achieve eccentric overload, a flywheel cylindrical shaft type with low moments of inertia is advised to be used.

This study investigates the effects of electron cyclotron current drive (ECCD) on the linear and nonlinear dynamics of energetic-particle (EP)-driven magnetohydrodynamics (MHD) instability (mode) in Heliotron J (HJ), using MEGA, a nonlinear hybrid EP-MHD simulation code. The effects of ECCD are included through the modification of the equilibrium magnetic field. Five MHD equilibria with plasma currents ( $I_\textrm p$ ) of −2.00, −1.00, 0.00, 0.50, and 1.00 kA are considered, where negative and positive $I_\textrm p$ represent counter and co-ECCD, respectively. To account for the EP finite charge-exchange loss observed in HJ, a bump-on-tail velocity distribution is assumed for EP. The study finds that the stabilization trends in terms of the linear growth rate ( $\gamma \omega_A^{-1}$ ) are qualitatively similar to the FAR3D linear simulation and experimental results. In addition to the enhancements of the local magnetic shear and continuum damping by ECCD as proposed in previous studies, the study suggests that changes in the linear EP and shear Alfvén wave resonance are another important factor, especially for the $n/m = 1/2$ mode. The study shows that in the currentless equilibrium, the high-velocity toroidicity-induced resonance between the $n/m = 1/2$ mode and the co-passing EP ( $L = -1$ ) has the highest EP energy transfer rate, but is located slightly below the NBI injection velocity. The co-ECCD and cntr-ECCD can shift this resonance into higher and lower velocity regions, respectively. This can lead to resonance removal for co-ECCD, while cntr-ECCD can initially increase the number of resonant EPs for a small value of shift. If the shift of the resonance by cntr-ECCD is sufficiently large, the study observes stabilization due to the reduction in the EP population in the low-velocity region. The study also finds that changes in resonance affect nonlinear dynamics such as EP transport and frequency chirping. The convective transport of the co- and counter-passing EPs can be controlled, which can only be achieved for energetic-particle-mode due to the asymmetry in the resonance velocity between co- and cntr-passing EPs. The changes in the frequency chirping from the downward chirping branch to the upward chirping branch can also be explained by the changes in the resonance velocity caused by ECCD.

This study aimed to quantify the external match loads (EMLs) of a Portuguese u-23 soccer team, competing at the highest national level for the age group, comparing players with different starting status throughout a competitive season and specific blocks. Thirty-five outfield soccer players were split into three groups for the entire season analysis and for each 3-month block, based on the percentage of games played as a starter. The three groups consisted of “starters” (≥55% of the games as a starter), “fringe” (30–54%), and “non-starters” (p < 0.05) were found for total distance (TD), exposure time, and the number of accelerations and decelerations between starters and non-starters throughout the season (d = 0.73 to 1.08), and within each block (d = 0.59 to 1.68). Differences were also found between starters and fringe players for the number of accelerations in Block 2 (p = 0.03; d = 0.69), and TD (p = 0.006; d = 1) and exposure time (p = 0.006; d = 0.95) in Block 3. Differences in the EML were almost always accompanied by large differences in game time. Our results highlight the differences in the EML of starters and non-starters, emphasizing the need for compensatory training, especially with players that obtain significantly less playing time, to prepare the players for match demands (e.g., high-intensity efforts such as sprinting, accelerations, and decelerations).

A major objective of lattice QCD is the computation of hadronic matrix elements. The standard method is to use three-point and four-point correlation functions. An alternative approach, requiring only the computation of two-point correlation functions is to use the Feynman-Hellmann theorem. In this talk we develop this method up to second order in perturbation theory, in a context appropriate for lattice QCD. This encompasses the Compton Amplitude (which forms the basis for deep inelastic scattering) and hadron scattering. Some numerical results are presented showing results indicating what this approach might achieve.

The EF-hand calcium (Ca2+)-binding protein, neuronal Ca2+ sensor-1 (NCS-1/frequenin), is predominantly expressed in neuronal tissues and plays a crucial role in neuronal functions, including synaptic transmission and plasticity. NCS-1 has diverse functional roles, as elucidated in the past 15 years, which include the regulation of phosphatidylinositol 4-kinase IIIβ (PI-4K-β) and several ion channels such as voltage-gated K+ and Ca2+ channels, the D2 dopamine receptors, and inositol 1,4,5-trisphosphate receptors (InsP3Rs). Functional analyses demonstrated that NCS-1 enhances exocytosis and neuronal survival after injury, as well as promotes learning and memory in mice. NCS-1 is also expressed in the heart including the Purkinje fibers (PFs) of the conduction system. NCS-1 interacts with KV4 K+ channels together with dipeptidyl peptidase-like protein-6 (DPP-6), and this macromolecule then composes the transient outward current in PFs and contributes to the repolarization of PF action potential, thus being responsible for idiopathic arrhythmia. Moreover, NCS-1 expression was reported to be significantly high at the immature stage and at hypertrophy in adults. That report demonstrated that NCS-1 positively regulates cardiac contraction in immature hearts by increasing intracellular Ca2+ signals through interaction with InsP3Rs. With the related signals, NCS-1 activates nuclear Ca2+ signals, which would be a mechanism underlying hormone-induced cardiac hypertrophy. Furthermore, NCS-1 contributes to stress tolerance in cardiomyocytes by activating mitochondrial detoxification pathways, with a key role in Ca2+-dependent pathways. In this review, we will discuss recent findings supporting the functional significance of NCS-1 in the brain and heart and will address possible underlying molecular mechanisms.