Phase Of Cycle Research Articles

Attention-Based Neural Network for Cardiac MRI Segmentation: Application to Strain and Volume Computation

ContextDeep learning algorithms have been widely used for cardiac image segmentation. However, most of these architectures rely on convolutions that hardly model long-range dependencies, limiting their ability to extract contextual information. Moreover, the traditional U-net architecture suffers from the difference of semantic information between feature maps of the encoder and decoder (also known as the semantic gap). Material and methodTo address this issue, a new network architecture relying on attention mechanism was introduced. Swin Filtering Blocks (SFB), that use Swin Transformer blocks in a cross-attention manner, were added between the encoder and the decoder to filter information coming from the encoder based on the feature map from the decoder. Attention was also employed at the lowest resolution in the form of a transformer layer to increase the receptive field of the network.We conducted experiments to assess both generalization capability and to evaluate how training on all frames of the cardiac cycle rather than only the end-diastole and end-systole impacts strain and segmentation performances. Results and conclusionVisual inspection of feature maps suggested that Swin Filtering Blocks contribute to the reduction of the semantic gap. Performing attention between all patches using a transformer layer brought higher performance than convolutions. Training the model with all phases of the cardiac cycle resulted in slightly more accurate segmentations while leading to a more noticeable improvement for strain estimation. A limited decrease in performance was observed when testing on out-of-distribution data, but the gap widens for the most apical slices.

Emergence of shared leadership in project teams: The role of events

The interest in project leadership research has expanded towards shared leadership practices, and shared leadership is a noteworthy alternative for traditional project management approaches. Despite the growing interest in shared leadership, the role of events in the emergence of shared leadership remains unclear. The aim of our research was to identify what kind of events trigger or hinder the emergence of shared leadership in project teams. Our qualitative research data from interviews with 31 project team members was collected in five different organizations. Activity theory was chosen as the analytical tool to explore the events affecting the emergence of shared leadership. We found event chains that trigger and hinder the emergence of shared leadership during the different phases of a project life cycle. Our research contributes to project leadership research by shedding light on the role of events in the emergence of shared leadership.

Experimental study on combustion instability characteristics in a pre-chamber natural gas engine under lean burn conditions

Pre-chamber jet ignition is a key technology for future high-efficiency natural gas (NG) engines. It can achieve fast and stable combustion through excellent ignition performance. However, there are still some challenges, such as high combustion instability near the lean burn limit and the narrow engine operating range. Therefore, this paper investigates the combustion instability of a pre-chamber NG engine under ultra-diluted conditions by experimental method. At two engine loads, experiments are carried out with different jet ignition intensity schemes to study the effect of jet ignition intensity on the cyclic combustion variations. Then, the combustion instability characteristics of the pre-chamber NG engine are studied by cyclic variation analysis and phase space reconstruction. The results show that with the increase in the jet ignition intensity, the cyclic combustion variations decrease, and the cyclic variation coefficient of the indicated mean effective pressure decreases to below 2%. The lean burn limit of the pre-chamber natural gas engine is extended to an excess air ratio of 2.0. The operation instability of the pre-chamber NG engine is mainly due to cyclic variations in the ignition and combustion process. The nonlinear dynamic analysis shows that the combustion process in the lean burn pre-chamber NG engine behaves with chaotic characteristics under the operating conditions of low jet ignition intensity. As the jet ignition intensity increases, the combustion stability is improved and the cycle-to-cycle variations change from fairly deterministic to more stochastic behavior. The chaotic characteristics of the combustion process become weaker. In conclusion, it is of great importance to generate stable and high ignition intensity jets for reducing combustion instability and improving combustion efficiency in lean burn pre-chamber NG engines.

Geochronology (zircon U-Pb, Hf, O isotopes), provenance analysis, and tectonic setting of the Paleoproterozoic Karrat Group and supracrustal rocks of the Rinkian fold belt, West Greenland

We use zircon U-Pb, Hf and O isotopes to constrain the depositional ages and provenance of metasedimentary rocks of the Paleoproterozoic Karrat Group of West Greenland and to understand the tectonic processes leading to basin development on the eastern Rae craton. An older supracrustal assemblage (Qeqertarssuaq complex) deposited after ca. 2.6 Ga is separated by an unconformity with a younger supracrustal assemblage (the Karrat Group). The Qaarsukassak Formation at the base of the Karrat Group was deposited after ca. 2.0 Ga, with dominantly Archean age modes. The youngest siliciclastic rocks (Nûkavsak and Mârmorilik formations) in the Karrat Group have maximum depositional ages ranging from ca. 1980 to 1950 to 1900 Ma and contain dominant detrital zircon age modes between ca. 2.50 and 1.93 Ga. A ca. 1.92 Ga supracrustal assemblage referred to as the northern domain (Karrat Group, sensu lato) is geographically separated from the Karrat Group (sensu stricto) by the Prøven igneous complex. The stratigraphy and detrital zircon profiles are compared to broadly coeval sedimentary units on the Rae craton and a unifying model of their deposition is presented. The Rae craton is the dominant detritus source; initially these sources were mostly local, changing to a mix of local and distal sources including the western Rae craton. The tectonic setting of the Karrat basin transitioned from extensional to convergent to collisional during its basin evolution, reflecting Wilson cycle phases within an epeiric sea. Accordingly, zircon Hf isotopes in our dataset track the evolution of the opening and closing of the Manikewan Ocean. Detrital zircon Hf isotopes in our dataset reveal a greater proportion of juvenile detritus (especially ca. 2.15–1.95 Ga) than is known from the currently exposed crustal record, pointing to the importance of the detrital zircon record for understanding Paleoproterozoic crustal and tectonic evolution.

Activity of predators in seabird colonies decreases during the darkest compared to the brightest phase of the diel cycle below, but not above, the Arctic Circle

ABSTRACT Predator activity can structure communities temporally and influence the spatial distribution of prey. Yet, despite the influence this may have on prey species’ activity or geographic persistence, our understanding of whether diel predator activity changes geographically remains limited. Here, we conduct a case study to test whether predator activity during the darkest phase of the diel cycle increases with the duration of daylight (i.e. photoperiod) at high latitudes during summer, aligning with the photoperiod constraint hypothesis. Using both observations and experiments at one seabird colony above and one below the northern polar (Arctic) circle, we compared predator activity between the brightest and darkest phases of the diel cycle. Avian predator counts were greater and nest predation events were more common during the brightest phase of the diel cycle below the Arctic Circle (i.e. where the sun goes below the horizon) but similar across phases during polar summer (i.e. above the Arctic Circle when the sun does not set). Our results highlight the potential influence of light on activity of predator communities and suggest a possible latitudinal limit to the advantage gained by dark-active strategies for avoidance of visually hunting predators.

Energy and environmental evaluation and comparison of a diesel-electric hybrid tractor, a conventional tractor, and a hillside mini-tiller using the life cycle assessment method

Currently, electrification, especially hybrid solutions, still represents the most promising option to improve energy efficiency, emissions, and productivity for agricultural machinery. Agricultural machinery in China's mountainous areas is represented by quantities of small conventional tractors and hillside mini-tillers (HMTs), which are highly fuel-intensive and polluting. Effective measures need to be taken to reduce their environmental impacts. Thus, a diesel-electric hybrid tractor (DHT) was designed and developed. The life cycle assessment (LCA) method was used to assess and compare the energy consumption and environmental impacts of the DHT, an internal combustion engine tractor (ICET), and an HMT in this study. Comparative results present that the ICET had the most contribution to acidification potential (AP), eutrophication potential (EP), and respiratory inorganics (RI), while the HMT created the most to primary energy demand (PED), global warming potential (GWP), and photochemical ozone creation potential (POCP). The DHT had the lowest contribution to six environmental impact indicators, 5.1%–68.9% lower than those of ICET and HMT. Among the six phases in the life cycle, the Pump-to-Wheel (PTW) phase consumed the most energy (65.9%–78.5%) and brought about the largest environmental impacts (54.2%–94.7%), followed by the Well-to-Pump (WTP) phase (4.0%–37.3%). Increasing the proportion of electricity generation from non-fossil fuels in 2030 showed positive effects on saving energy and reducing environmental impacts for the ICET, DHT, and HMT, with the DHT benefiting the most. Discoveries in this study can contribute to the research and development of the DHT and the electrification of small agricultural machinery.

Combining In Vitro, In Vivo, and Network Pharmacology Assays to Identify Targets and Molecular Mechanisms of Spirulina-Derived Biomolecules against Breast Cancer.

The current research employed an animal model of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland carcinogenesis. The estrogen receptor-positive human breast adenocarcinoma cell line (MCF-7) was used for in vitro analysis. This was combined with a network pharmacology-based approach to assess the anticancer properties of Spirulina (SP) extract and understand its molecular mechanisms. The results showed that the administration of 1 g/kg of SP increased the antioxidant activity by raising levels of catalase (CAT) and superoxide dismutase (SOD), while decreasing the levels of malonaldehyde (MDA) and protein carbonyl. A histological examination revealed reduced tumor occurrence, decreased estrogen receptor expression, suppressed cell proliferation, and promoted apoptosis in SP protected animals. In addition, SP disrupted the G2/M phase of the MCF-7 cell cycle, inducing apoptosis and reactive oxygen species (ROS) accumulation. It also enhanced intrinsic apoptosis in MCF-7 cells by upregulating cytochrome c, Bax, caspase-8, caspase-9, and caspase-7 proteins, while downregulating Bcl-2 production. The main compounds identified in the LC-MS/MS study of SP were 7-hydroxycoumarin derivatives of cinnamic acid, hinokinin, valeric acid, and α-linolenic acid. These substances specifically targeted three important proteins: ERK1/2 MAPK, PI3K-protein kinase B (AKT), and the epidermal growth factor receptor (EGFR). Network analysis and molecular docking indicated a significant binding affinity between SP and these proteins. This was verified by Western blot analysis that revealed decreased protein levels of p-EGFR, p-ERK1/2, and p-AKT following SP administration. SP was finally reported to suppress MCF-7 cell growth and induce apoptosis by modulating the PI3K/AKT/EGFR and MAPK signaling pathways suggesting EGFR as a potential target of SP in breast cancer (BC) treatment.

Integrated metabolomics and proteomics analyses to reveal anticancer mechanism of hemp oil extract in colorectal cancer

Cannabis sativa L., with a rich history in Chinese folk medicine, includes hemp strains that offer substantial economic and medical benefits due to their non-addictive properties. Hemp has demonstrated various pharmaceutical activities, including anti-inflammatory, antioxidant, and anti-tumor effects. This study explores the potential of hemp oil extract (HOE) in treating colorectal cancer (CRC). Despite its promise, the specific anticancer mechanisms of HOE have not been well understood. To elucidate these mechanisms, we employed mass spectrometry-based metabolomics and proteomics to investigate the global effects of HOE on CRC cells. Additionally, bioinformatics approaches, including bulk RNA-seq and single-cell RNA-seq, were used to identify gene expression differences and cellular heterogeneity. The results were validated using flow cytometry, western blotting, and immunohistochemistry. Our findings reveal that HOE induces significant alterations in purine metabolism pathways, down-regulates c-MYC, and inhibits the expression of cell cycle-related proteins such as CCND1, CDK4, and CDK6, leading to cell cycle arrest in the G1 phase. This comprehensive analysis demonstrates that HOE effectively blocks the cell cycle in the G1 phase, thereby inhibiting colorectal cancer cell proliferation. These findings provide experimental evidence supporting the potential therapeutic use of hemp in medicine.

The natural menstrual cycle revisited – can natural cycle be trusted

BackgroundThe serum progesterone (P4) level during the luteal phase (LP) plays a crucial role in the initiation and maintenance of pregnancy. However, it is unclear whether the natural cycle consistently provides the best endocrine profile and whether mid-luteal serum P4 levels are always sufficient to support implantation and early pregnancy. The question has become more relevant in relation to fertility treatment, as more frozen embryo transfer cycles are performed in the natural cycle. Moreover, can serum hormone levels and covariates measured during the follicular phase (FP), such as Follicle Stimulation Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), Anti-Mullerian Hormone (AMH) and Antral Follicle Count (AFC), be used to predict P4 levels during the luteal phase (LP)?ResultsThis observational prospective cohort study analysed 26 healthy women with a cycle length between 21–35 days and a body mass index (BMI) < 30 kg/m2. Blood sampling started on the fifth day of the menstrual cycle and continued every fifth day until the next cycle. The procedure was repeated for a total of three cycles. The study found that only ten women had a P4 level greater than 30 nmol/L on cycle day 20 or 25 in all three cycles. In total, only 45 cycles out of 77 cycles had serum P4 levels ≥ 30 nmol/L.The E2 level ≥ 345 pmol/L on cycle day 10 proved to be predictive of a P4 level of ≥ 30 nmol/L on either day 20 or day 25 with a sensitivity of 57% and a specificity of 89%. No other covariates, including the FSH level cycle day 5, LH levels during the follicular phase, age, weight, AFC and AMH cycle day 5 correlated with LP P4 levels.ConclusionsA significant correlation between FP E2 levels cycle day 5 (> 131pmol/L) and cycle day 10 (> 345pmol/L) and a LP P4 level ≥ 30 nmol/l was found; thus, the FP E2 level is a predictor of corpus luteum competence. Our findings highlight the existence of suboptimal P4 levels during the LP and a significant inter-individual and intra-cycle variation in P4 levels during the LP in regular menstruating women.

Oxytocin and cortisol concentrations in urine and saliva in response to physical exercise in humans

BackgroundWhile peripheral markers of endogenous oxytocin and glucocorticoid release are widely employed in psychological and behavioural research, there remains uncertainty regarding the effectiveness of saliva and urine samples in accurately capturing fluctuating hormone levels in response to relevant stimuli. In addition, it is unclear whether and under which conditions, urinary concentrations correlate with salivary levels of oxytocin and cortisol. MethodsIn the present study, two groups of healthy adult male and female participants (N=43) provided heart rate, saliva, and urine samples before and after exercising at different durations and intensities (3 ×10 min of running vs. 60 min of running). Effects of age, gender, cycle phase, and previous running experience were considered in the statistical analyses. Concentrations of oxytocin and cortisol were analysed in both saliva, and urine using validated assays. ResultsRunners of both groups had significantly increased oxytocin concentrations in urine and saliva after running than before. Oxytocin in saliva was elevated after 10 min and peaked after 30 min of running. Only participants of the long-running group showed an increase in urinary cortisol concentrations following exercise (and only after 90 min of stimulus onset), and neither group had a significant increase in salivary cortisol levels. Oxytocin rise in urine and saliva from basal to post-run was strongly and significantly correlated, as was cortisol rise from basal to post-rest, but no correlations between absolute hormone concentrations were found for oxytocin. ConclusionsOur results show that both urine and saliva are useful body fluids that can provide meaningful results when measuring oxytocin and cortisol concentrations after a physical stimulus. While temporal resolution may be better with salivary sampling as higher sampling frequency is possible, signal strength and robustness were better in urinary samples. Importantly, we report a strong correlation between the magnitude of change in oxytocin and cortisol concentrations in urine and saliva following physical exercise, but no correlations between absolute oxytocin concentrations in the two substrates.

In vitro quantification of stent-graft behaviour during chimney thoracic endovascular aortic repair.

To quantify dynamic gutter phenomena and endograft deformations during double chimney thoracic endovascular aortic repair (ch-TEVAR) in a physiological model of the thoracic aorta subjected to pulsatile haemodynamic conditions. Two in vitro procedures revascularizing the brachiocephalic trunk and left common carotid artery were performed representing both balloon-expandable (BE, Ankura-BeGraft) and self-expandable (SE, Ankura-Viabahn) double ch-TEVAR configurations. Retrospectively gated computed tomography (CT) was used to evaluate endograft behaviour. Device interactions were characterised according to gutter volume, gutter surface deviation, and endograft deformation (D-ratio) at end-diastolic and peak-systolic aortic pressure. Use of BE chimney grafts resulted in three times total gutter volume compared to SE chimney grafts. Gutter volumes were observed to vary dynamically between the end-diastolic and peak-systolic phases of the cardiac cycle, with the most substantial change associated with the BE configuration. Chimney graft deformations were dependent on device type, with SE devices exhibiting up to twice the deformation as BE devices. When adjacent, SE chimney grafts were observed to support each other, and thus tended towards a more consistently circular shape. Gutter and chimney graft behaviour were dependent on device type, and exhibited both spatial and temporal variability. This study emphasises notable differences between BE and SE double ch-TEVAR configurations which should be considered when evaluating risk of endoleak. The findings reported here also support the use of gated CT to better identify device-related complications with ch-TEVAR, and can be used in the design of next generation devices.

EXCOR membrane motion analyzer (EMMA) to quantify and assess hemodynamic performance of the EXCOR pediatric heart assist device.

Pediatric heart failure is associated with high mortality rates and is a current clinical burden. There is only one FDA approved pediatric VAD, Berlin Heart EXCOR, for treatment. Thrombo-embolic complications are a significant clinical challenge, which can lead to devastating complications such as stroke and impair efficient EXCOR function. Currently, clinicians perform largely qualitative periodic assessment of EXCOR operation by observing the motion of a rapidly moving membrane, which can be prone to human error and can lead to missing out on crucial information. In this study, we design and implement a quantitative early warning system for accurate and quantitative assessment of the EXCOR membrane, named EXCOR Membrane Motion Analyzer (EMMA). Using a combination of image analysis, computer vision and custom designed algorithm, we perform rigorous frame by frame analysis of EXCOR membrane video data. We developed specialized metrics to identify relative smoothness between successive peaks, time between peaks and overall smoothness indicators to quantify and compare between multiple cases. Our results demonstrate that EMMA can successfully identify the motion and wrinkles on each video frame and quantify the smoothness and identify the phases of each cardiac cycle. Moreover, EMMA can obtain the smoothness of each frame and the temporal evolution of membrane smoothness across all image frames for the video sequence. EMMA allows for a fast, accurate, quantitative assessment to be completed and reduces user error. This enables EMMA to be used effectively as an early warning system to rapidly identify device abnormalities.

Fiscal rules and economic cycles: Quality (always) Matters

This paper investigates the role of fiscal rules in managing public debt, particularly focusing on their efficacy during different phases of economic cycles. Analyzing Balance, Expenditure, and Debt Fiscal Rules, the study finds that their impact on debt reduction is significantly influenced by the quality of the fiscal framework and the economic cycle phase. Moreover, factors like legal basis, procedural framework, and political stability are identified as key to ensuring compliance with fiscal objectives. Our results suggest that fiscal rules are most effective in reducing debt during positive economic cycles, with the design and institutional support playing a crucial role. This has important policy implications, particularly in the context of the debt increase after the Covid-19 pandemic.

Ganoderic acid a derivative induces apoptosis of cervical cancer cells by inhibiting JNK pathway

ObjectiveGanoderic acid A can inhibit the proliferation and promotes the apoptosis of cancer cells. Surprisingly, the molecular mechanisms underlying the anti-cancer effects of ganoderic acid A still remain poorly defined. Ganoderic acid A derivative (GaAD19) is an effective ingredient obtained by structural modification of ganoderic acid A. The purpose of this study was to evaluate the anti-proliferation effect of GaAD19 on cervical cancer cells. MethodsThrough the HeLa cervical cancer cell model, the drug target of GaAD19 was predicted using the SwissTargetPrediction database and molecular docking. Subsequently, computer analysis results were verified by a series of molecular biology experiments, such as flow cytometry, Western blot, immunocytochemical staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), quantitative real time polymerase chain reaction (qPCR), and so on. Then, pathway agonists and inhibitors were used to investigate the mechanism of GaAD19. Finally, the mouse model of cervical cancer was established to evaluate the inhibitory effect of GaAD19 on tumor growth in U14 cervical cancer mice. ResultsGaAD19 induced apoptosis and inhibited the growth of tumors. It also blocked the transition from the G1 to the S phase of the cell cycle. However, in the presence of a c-Jun N-terminal kinase (JNK)agonist, the effects of GaAD19 on the proliferation, apoptosis, and cell cycle transition of cancer cells were suppressed. ConclusionsThis study showed that GaAD19 can play an anti-cervical cancer role by inhibiting the JNK signaling pathway. These results will be helpful in further exploring the mechanism of GaAD19 in the treatment of cervical cancer.

Design, synthesis, crystal structure and anticancer activity of organotin(IV)-rhein carboxylates

Two new rhein-organotin complexes Ph3Sn(O2CC14H7O4) (RS01) and Cy3Sn(O2CC14H7O4) (RS02) were synthesized and characterized by elemental analysis, IR, 1H NMR, 13C NMR, 119 Sn NMR, X-ray crystallography and thermo-gravimetric analysis. Both complexes has a triclinic crystal system P-1 space group and one-dimensional supramolecular chain structure. The MTT results demonstrated that rhein's anticancer activity was effectively increased by introducing organotin, RS01 and RS02 exhibited excellent anticancer activity in vitro, significantly superior to cisplatin and mitoxantrone. Interestingly, despite the fact that RS01 and mitoxantrone share the same 9,10-anthraquinone scaffold structure, RS01 not only showed high anticancer activity but also much lower nephrotoxicity than mitoxantrone. Flow cytometry showed that RS01 could significantly induce cell apoptosis and arrest cell cycle in G2 phase. Molecular docking and UV–Vis absorption spectra suggested that RS01 may be intercalation with DNA. Furthermore, western blot results showed that RS01 activated the DNA damage critical protein γ-H2AX and regulated the expression level of the mitochondrial apoptotic pathway critical protein (Bax/Bcl-2). Thus, RS01 induced cell death may be mediated through DNA damage and mitochondrial pathways. As a result, RS01 has significant development and application potential as an anticancer agent.

Menstrual cycle-driven hormone concentrations co-fluctuate with white and gray matter architecture changes across the whole brain.

Cyclic fluctuations in hypothalamic-pituitary-gonadal axis (HPG-axis) hormones exert powerful behavioral, structural, and functional effects through actions on the mammalian central nervous system. Yet, very little is known about how these fluctuations alter the structural nodes and information highways of the human brain. In a study of 30 naturally cycling women, we employed multidimensional diffusion and T1-weighted imaging during three estimated menstrual cycle phases (menses, ovulation, and mid-luteal) to investigate whether HPG-axis hormone concentrations co-fluctuate with alterations in white matter (WM) microstructure, cortical thickness (CT), and brain volume. Across the whole brain, 17β-estradiol and luteinizing hormone (LH) concentrations were directly proportional to diffusion anisotropy (μFA; 17β-estradiol: β1 = 0.145, highest density interval (HDI) = [0.211, 0.4]; LH: β1 = 0.111, HDI = [0.157, 0.364]), while follicle-stimulating hormone (FSH) was directly proportional to CT (β1 = 0 .162, HDI = [0.115, 0.678]). Within several individual regions, FSH and progesterone demonstrated opposing relationships with mean diffusivity (Diso) and CT. These regions mainly reside within the temporal and occipital lobes, with functional implications for the limbic and visual systems. Finally, progesterone was associated with increased tissue (β1 = 0.66, HDI = [0.607, 15.845]) and decreased cerebrospinal fluid (CSF; β1 = -0.749, HDI = [-11.604, -0.903]) volumes, with total brain volume remaining unchanged. These results are the first to report simultaneous brain-wide changes in human WM microstructure and CT coinciding with menstrual cycle-driven hormone rhythms. Effects were observed in both classically known HPG-axis receptor-dense regions (medial temporal lobe, prefrontal cortex) and in other regions located across frontal, occipital, temporal, and parietal lobes. Our results suggest that HPG-axis hormone fluctuations may have significant structural impacts across the entire brain.

Moderate-intensity aerobic exercise enhanced dopamine signaling in diet-induced obese female mice without preventing body weight gain

Obesity continues to rise in prevalence and financial burden despite strong evidence linking it to an increased risk of developing several chronic diseases. Dopamine response and receptor density are shown to decrease under conditions of obesity. However, it is unclear if this could be a potential mechanism for treatment without drugs that have a potential for abuse. Therefore, the aim of this study was to investigate whether moderate-intensity exercise could reduce body weight gain and the associated decreases in dopamine signaling observed with high-fat diet-induced adiposity. We hypothesized that exercise would attenuate body weight gain and diet-induced inflammation in high-fat (HF)-fed mice, resulting in dopamine signaling (release and reuptake rate) comparable to sedentary, low-fat (LF)-fed counterparts. This hypothesis was tested using a mouse model of diet-induced obesity (DIO) and fast-scan cyclic voltammetry to measure evoked dopamine release and reuptake rates. Although the exercise protocol employed in this study was not sufficient to prevent significant body weight gain, there was an enhancement of dopamine signaling observed in female mice fed a HF diet that underwent treadmill running. Additionally, aerobic treadmill exercise enhanced the sensitivity to amphetamine (AMPH) in this same group of exercised, HF-fed females. The estrous cycle might influence the ability of exercise to enhance dopamine signaling in females, an effect not observed in male groups. Further research into females by estrous cycle phase, in addition to determining the optimal intensity and duration of aerobic exercise, are logical next steps.

Inter-ELM pedestal turbulence dynamics dependence on q95 and temperature gradient

A series of dedicated experiments from the DIII-D tokamak provide spatially and temporally resolved measurements of electron density and temperature, and multiscale and multichannel fluctuations over a wide range of conditions. Measurements of long wavelength density fluctuations in the type-I ELMing H-mode pedestals routinely reveal a coexistence of multiple instabilities that exhibit dramatic different dynamic behaviors as q95 and temperature gradients are varied, apparently responsible for limiting pedestal temperature profiles. Two distinct frequency bands of density fluctuations are modulated by an ELM cycle with frequency above 200 kHz propagating in the electron diamagnetic direction in the lab frame (electron mode) and below 200 kHz propagating in the ion diamagnetic direction (ion mode). The electron mode amplitude peaks near the electron temperature gradient region and increases with q95 which seems to be correlated with the increased χe at higher q95, similar to the characteristics expected for the micro-tearing mode (MTM). At higher q95, during the inter-ELM period, the ion mode decays at the later phase of the ELM cycle. Consistently, the poloidal correlation length of the ion mode is also found to reduce, which suggests the possible E × B flow shear suppression of the ion mode at the later phase of the ELM cycle as the Er well recovers. In contrast, the electron mode grows during the ELM cycle and reaches saturation at around 50%–60% of the ELM period. Linear gyrokinetic simulations find the MTMs to be the most unstable mode in the pedestal electron temperature gradient region. The higher q95 and lower magnetic shear destabilize the MTMs. These observations provide key insights into the underlying physics of multifield properties and a rich dataset of experimental ‘fingerprints’ that enable new tests of theoretical pedestal models and lead to the development of a predictive model for pedestal formation on the ITER and future burning plasma experiments.

Cellular endosomal potassium ion flux regulates arenavirus uncoating during virus entry.

Lymphocytic choriomeningitis virus (LCMV) is an enveloped and segmented negative-sense RNA virus classified within the Arenaviridae family of the Bunyavirales order. LCMV is associated with fatal disease in immunocompromised populations and, as the prototypical arenavirus member, acts as a model for the many highly pathogenic members of the Arenaviridae family, such as Junín, Lassa, and Lujo viruses, all of which are associated with devastating hemorrhagic fevers. To enter cells, the LCMV envelope fuses with late endosomal membranes, for which two established requirements are low pH and interaction between the LCMV glycoprotein (GP) spike and secondary receptor CD164. LCMV subsequently uncoats, where the RNA genome-associated nucleoprotein (NP) separates from the Z protein matrix layer, releasing the viral genome into the cytosol. To further examine LCMV endosome escape, we performed an siRNA screen which identified host cell potassium ion (K+) channels as important for LCMV infection, with pharmacological inhibition confirming K+ channel involvement during the LCMV entry phase completely abrogating productive infection. To better understand the K+-mediated block in infection, we tracked incoming virions along their entry pathway under physiological conditions, where uncoating was signified by separation of NP and Z proteins. In contrast, K+ channel blockade prevented uncoating, trapping virions within Rab7 and CD164-positive endosomes, identifying K+ as a third LCMV entry requirement. K+ did not increase GP-CD164 binding or alter GP-CD164-dependent fusion. Thus, we propose that K+ mediates uncoating by modulating NP-Z interactions within the virion interior. These results suggest K+ channels represent a potential anti-arenaviral target.IMPORTANCEArenaviruses can cause fatal human disease for which approved preventative or therapeutic options are not available. Here, using the prototypical LCMV, we identified K+ channels as critical for arenavirus infection, playing a vital role during the entry phase of the infection cycle. We showed that blocking K+ channel function resulted in entrapment of LCMV particles within late endosomal compartments, thus preventing productive replication. Our data suggest K+ is required for LCMV uncoating and genome release by modulating interactions between the viral nucleoprotein and the matrix protein layer inside the virus particle.

Diastolic Dysfunction in Hypertension: A Comprehensive Review of Pathophysiology, Diagnosis, and Treatment.

Diastolic dysfunction refers to impaired relaxation or filling of the ventricles during the diastolic phase of the cardiac cycle. Left ventricular diastolic dysfunction (LVDD) is common in hypertensive individuals and is associated with increased morbidity and mortality. LVDD serves as a critical precursor to heart failure (HF), particularly heart failure with preserved ejection fraction (HFpEF). The pathophysiology of LVDD in hypertension is complex, involving alterations in cardiac structure and function, neurohormonal activation, and vascular stiffness. While the diagnosis of LVDD relies primarily on echocardiography, management remains challenging due to a lack of specific treatment guidelines for LVDD. This review offers an overview of the pathophysiological mechanisms underlying LVDD in hypertension, diagnostic methods, clinical manifestations, strategies for managing LVDD, and prospects for future research.