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2.
Opt Express ; 32(8): 13419-13437, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38859313

ABSTRACT

Silicon microring resonators serve as critical components in integrated photonic neural network implementations, owing to their compact footprint, compatibility with CMOS technology, and passive nonlinear dynamics. Recent advancements have leveraged their filtering properties as weighting functions, and their nonlinear dynamics as activation functions with spiking capabilities. In this work, we investigate experimentally the linear and nonlinear dynamics of microring resonators for time delay reservoir computing, by introducing an external optical feedback loop. After effectively mitigating the impact of environmental noise on the fiber-based feedback phase dependencies, we evaluate the computational capacity of this system by assessing its performance across various benchmark tasks at a bit rate of few Mbps. We show that the additional memory provided by the optical feedback is necessary to achieve error-free operation in delayed-boolean tasks that require up to 3 bits of memory. In this case the microring was operated in the linear regime and the photodetection was the nonlinear activation function. We also show that the Santa Fe and Mackey Glass prediction tasks are solved when the microring nonlinearities are activated. Notably, our study reveals competitive outcomes even when employing only 7 virtual nodes within our photonic reservoir. Our findings illustrate the silicon microring's versatile performance in the presence of optical feedback, highlighting its ability to be tailored for various computing applications.

3.
Public Health Pract (Oxf) ; 7: 100512, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38846106

ABSTRACT

Objectives: Research on links between social, geographic, and cultural determinants of health has been thwarted by inadequate measures of culture. The purpose of this study was to improve the measurement of community culture, defined as shared patterns of attitudes and behaviors among people within a neighborhood that distinguish it from others, and to examine dimensions of culture, independent of socioeconomic and demographic factors, and their relationships with health. Study design: A survey research design with correlational analyses was used. Methods: A survey packet including the Community Culture Survey - Revised (CCS-R), demographic, health, and other individual-level measures was administered through convenience sampling across the United States (US) and to a sample in Thailand from 2016 to 2018. US county-level variables were obtained from zip codes. Results: 1930 participants from 49 US states (n = 1592) and Thailand (n = 338) completed all CCS-R items, from which 12 subscales were derived: Social Support & Connectedness, Responsibility for Self & Others, Family Ties & Duties, Social Distress, Urban Diversity, Discontinuity, Church-Engaged, External Resource-Seeking, Locally Owned Business-Active, Power Deference, Next Generation Focus, and Self-Reliance. Neighborhood culture subscale scores varied more by geography than by participant's demographics. All subscales predicted one or more health indicator, and some of these relationships were significant after adjusting for participant age and county-level socioeconomic variables. Most of the significant differences on subscales by race/ethnicity were no longer significant after adjusting for participant's age and county-level socioeconomic variables. Most rural/urban and regional differences in culture within the US persisted after these adjustments. Based on correlational analyses, Social Support & Connectedness and Responsibility for Self & Others were the best predictors of participants' overall health and quality of life, and Responsibility for Self & Others was the best predictor (inversely) of the CDC's measures of social vulnerability. Conclusions: Neighborhood culture is measurable, multi-dimensional, distinct from race/ethnicity, and related to health even after controlling for age and socioeconomic factors. The CCS-R is useful for advancing research and practice addressing the complex interactions between individuals, their neighborhood communities, and health outcomes.

4.
Elife ; 132024 Jun 13.
Article in English | MEDLINE | ID: mdl-38869942

ABSTRACT

Movement is a key feature of animal systems, yet its embryonic origins are not fully understood. Here, we investigate the genetic basis underlying the embryonic onset of movement in Drosophila focusing on the role played by small non-coding RNAs (microRNAs, miRNAs). To this end, we first develop a quantitative behavioural pipeline capable of tracking embryonic movement in large populations of fly embryos, and using this system, discover that the Drosophila miRNA miR-2b-1 plays a role in the emergence of movement. Through the combination of spectral analysis of embryonic motor patterns, cell sorting and RNA in situs, genetic reconstitution tests, and neural optical imaging we define that miR-2b-1 influences the emergence of embryonic movement by exerting actions in the developing nervous system. Furthermore, through the combination of bioinformatics coupled to genetic manipulation of miRNA expression and phenocopy tests we identify a previously uncharacterised (but evolutionarily conserved) chloride channel encoding gene - which we term Movement Modulator (Motor) - as a genetic target that mechanistically links miR-2b-1 to the onset of movement. Cell-specific genetic reconstitution of miR-2b-1 expression in a null miRNA mutant background, followed by behavioural assays and target gene analyses, suggest that miR-2b-1 affects the emergence of movement through effects in sensory elements of the embryonic circuitry, rather than in the motor domain. Our work thus reports the first miRNA system capable of regulating embryonic movement, suggesting that other miRNAs are likely to play a role in this key developmental process in Drosophila as well as in other species.


Subject(s)
MicroRNAs , Animals , MicroRNAs/metabolism , MicroRNAs/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/embryology , Gene Expression Regulation, Developmental , Movement , Embryo, Nonmammalian/metabolism , Drosophila/genetics , Drosophila/embryology , Drosophila Proteins/genetics , Drosophila Proteins/metabolism
5.
J Am Heart Assoc ; 13(13): e033544, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38904251

ABSTRACT

BACKGROUND: Prognostic markers and biological pathways linked to detrimental clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. METHODS AND RESULTS: We measured serum levels of 4123 unique proteins in 1117 patients with HFpEF enrolled in the PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) trial using a modified aptamer proteomic assay. Baseline circulating protein concentrations significantly associated with the primary end point and the timing and occurrence of total heart failure hospitalization and cardiovascular death were identified by recurrent events regression, accounting for multiple testing, adjusted for age, sex, treatment, and anticoagulant use, and compared with published analyses in 2515 patients with heart failure with reduced ejection fraction from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbidity-Mortality in Patients With Chronic Heart Failure) clinical trials. We identified 288 proteins that were robustly associated with the risk of heart failure hospitalization and cardiovascular death in patients with HFpEF. The baseline proteins most strongly related to outcomes included B2M (ß-2 microglobulin), TIMP1 (tissue inhibitor of matrix metalloproteinase 1), SERPINA4 (serpin family A member 4), and SVEP1 (sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1). Overall, the protein-outcome associations in patients with HFpEF did not markedly differ as compared with patients with heart failure with reduced ejection fraction. A proteomic risk score derived in patients with HFpEF was not superior to a previous proteomic score derived in heart failure with reduced ejection fraction nor to clinical risk factors, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or high-sensitivity cardiac troponin. CONCLUSIONS: Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis in the PARAGON-HF proteomic substudy. Our results demonstrate substantial similarities among serum proteomic risk markers for heart failure hospitalization and cardiovascular death when comparing clinical trial participants with heart failure across the ejection fraction spectrum. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifiers: NCT01920711, NCT01035255, NCT00853658.


Subject(s)
Aminobutyrates , Biomarkers , Drug Combinations , Heart Failure , Proteomics , Stroke Volume , Tetrazoles , Valsartan , Humans , Heart Failure/drug therapy , Heart Failure/blood , Heart Failure/physiopathology , Heart Failure/mortality , Proteomics/methods , Male , Female , Aged , Biomarkers/blood , Valsartan/therapeutic use , Stroke Volume/physiology , Aminobutyrates/therapeutic use , Middle Aged , Tetrazoles/therapeutic use , Biphenyl Compounds/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Aptamers, Nucleotide/therapeutic use , Prognosis , Ventricular Function, Left
6.
J Insect Physiol ; 155: 104650, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38777077

ABSTRACT

In animals, memory allows to remember important locations and conserve energy by not responding to irrelevant stimuli. However, memory formation and maintenance are metabolically costly, making it worthwhile to understand the mechanisms underlying different types of memory and their adaptive value. In this study, we investigated the memory persistence of Aedes aegypti mosquito larvae, after habituation to a visual stimulus. We used an automated tracking system for quantifying the response of mosquito larvae to the passage of a shadow, simulating an approaching predator. First, we compared different retention times, from 4 min to 24 h, and found that mosquito larvae only exhibited memory capabilities less than 3 h after training. Secondly, we investigated the role of inter-trial intervals in memory formation. In contrast to other aquatic invertebrates, mosquito larvae showed no long-term memory even at long inter-trial intervals (i.e., 5 min and 10 min). Our results are discussed in relation to the ecological constraints.


Subject(s)
Aedes , Habituation, Psychophysiologic , Larva , Memory, Long-Term , Animals , Larva/physiology , Larva/growth & development , Aedes/physiology , Aedes/growth & development , Memory, Long-Term/physiology , Habituation, Psychophysiologic/physiology , Memory, Short-Term/physiology
7.
Sci Rep ; 14(1): 12360, 2024 05 29.
Article in English | MEDLINE | ID: mdl-38811574

ABSTRACT

Impaired lung function, respiratory muscle weakness and exercise intolerance are present in COPD and contribute to poor prognosis. However, the contribution of the combination of these manifestations to define prognosis in COPD is still unknown. This study aimed to define cut-off points for both inspiratory and expiratory muscle strength (MIP and MEP, respectively) for mortality prediction over 42-months in patients with COPD, and to investigate its combination with other noninvasive established prognostic measures (FEV1, V̇O2peak and 6MWD) to improve risk identification. Patients with COPD performed pulmonary function, respiratory muscle strength, six-minute walk and cardiopulmonary exercise tests, and were followed over 42 months to analyze all-cause mortality. A total of 79 patients were included. The sample was mostly (91.1%) comprised of severe (n = 37) and very severe (n = 34) COPD, and 43 (54%) patients died during the follow-up period. Cut-points of ≤ 55 and ≤ 80 cmH2O for MIP and MEP, respectively, were associated with increased risk of death (log-rank p = 0.0001 for both MIP and MEP) in 42 months. Furthermore, MIP and MEP substantially improved the mortality risk assessment when combined with FEV1 (log-ranks p = 0.006 for MIP and p < 0.001 for MEP), V̇O2peak (log-rank: p < 0.001 for both MIP and MEP) and 6MWD (log-ranks: p = 0.005 for MIP; p = 0.015 for MEP). Thus, patients severely affected by COPD presenting MIP ≤ 55 and/or MEP ≤ 80 cmH2O are at increased risk of mortality. Furthermore, MIP and MEP substantially improve the mortality risk assessment when combined with FEV1, V̇O2peak and 6MWD in patients with COPD.


Subject(s)
Muscle Strength , Pulmonary Disease, Chronic Obstructive , Respiratory Muscles , Humans , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/mortality , Pulmonary Disease, Chronic Obstructive/diagnosis , Male , Female , Aged , Prognosis , Respiratory Muscles/physiopathology , Middle Aged , Respiratory Function Tests , Exercise Test
8.
J Asthma ; : 1-10, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38577973

ABSTRACT

BACKGROUND: Asthmatic children present variable degrees of airway inflammation, remodeling, and resistance, which correlate with disease control and severity. The chronic inflammatory process of the airway triggers airway remodeling, which reflects the degree of airway resistance. Pro-inflammatory and pro-fibrotic mediators are centrally involved in this process. OBJECTIVE: To investigate whether the levels of pulmonary and systemic pro-inflammatory and pro-fibrotic mediators present a correlation with the resistance of the respiratory system and of the proximal and distal airways. METHODS: 39 Asthmatic children (persistent mild and moderate) and 39 non-asthmatic children (both between 6 and 13 years old) were evaluated for anthropometric characteristics, lung function and mechanics, and pulmonary and systemic immune responses. RESULTS: Asthmatic children showed an increased number of blood eosinophils (p < 0.04), basophils (p < 0.04), monocytes (p < 0.002) and lymphocytes (p < 0.03). In addition, asthmatic children showed impaired lung function, as demonstrated by FEV1 (p < 0.0005) and FEV1/FVC (p < 0.004), decreased total resistance of the respiratory system (R5Hz; p < 0.009), increased resistance of the proximal airways (R20Hz; p < 0.02), increased elastance (Z5Hz; p < 0.02) and increased reactance (X5Hz; p < 0.002) compared to non-asthmatic children. Moreover, the following inflammatory factors were significantly higher in asthmatic than non-asthmatic children: GM-CSF in the breath condensate (BC) (p < 0.0001) and in the serum (p < 0.0001); TGF-beta in the BC (p < 0.0001) and in the serum (p < 0.004); IL-5 in the BC (p < 0.02) and in the serum (p < 0.01); IL-4 in the serum (p < 0.0002). CONCLUSIONS: Impulse oscillometry is a sensitive method to detect airway resistance in persistent mild and moderate asthmatic children, an event followed by increased levels of pro-inflammatory and pro-fibrotic mediators.

9.
Front Sports Act Living ; 6: 1380903, 2024.
Article in English | MEDLINE | ID: mdl-38638448

ABSTRACT

Introduction: Gaming is often labeled as sedentary behavior. However, competitive gaming, also known as esports, involves significant cognitive demands and may induce stress. This study aims to investigate whether the psychophysical demands during esports elicit a physiological stress response. Methods: Fourteen FIFA 21 and thirteen League of Legends players (23.3 ± 2.8 years) were recruited for the study. Heart rate (HR), root mean square of successive differences between normal heartbeats (RMSSD), peripheral and central blood pressure (BP), pulse wave velocity (PWV), and energy expenditure (EE) were assessed during supine rest, seated rest, and competitive FIFA or League of Legends matches. Results: No significant group × condition interactions were observed for any of the outcomes. However, there were significant increases in mean HR (p < 0.001, ηp2 = 0.383), RMSSD (p = 0.019, ηp2 = 0.226), peripheral systolic BP (p < 0.001, ηp2 = 0.588), peripheral diastolic BP (p = 0.005, ηp2 = 0.272), central systolic BP (p = 0.005; ηp2 = 0.369), central diastolic BP (p = 0.016, ηp2 = 0.313), PWV (p = 0.004, ηp2 = 0.333), and EE (p < 0.001, ηp2 = 0.721) during both games compared to the seated rest condition. Conclusion: Despite the sedentary nature of esports, the psychophysical demands appear to elicit physiological responses. Interestingly, no significant differences were found between the different game genres.

10.
PLoS Comput Biol ; 20(3): e1011921, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38452057

ABSTRACT

In an ever-changing visual world, animals' survival depends on their ability to perceive and respond to rapidly changing motion cues. The primary visual cortex (V1) is at the forefront of this sensory processing, orchestrating neural responses to perturbations in visual flow. However, the underlying neural mechanisms that lead to distinct cortical responses to such perturbations remain enigmatic. In this study, our objective was to uncover the neural dynamics that govern V1 neurons' responses to visual flow perturbations using a biologically realistic computational model. By subjecting the model to sudden changes in visual input, we observed opposing cortical responses in excitatory layer 2/3 (L2/3) neurons, namely, depolarizing and hyperpolarizing responses. We found that this segregation was primarily driven by the competition between external visual input and recurrent inhibition, particularly within L2/3 and L4. This division was not observed in excitatory L5/6 neurons, suggesting a more prominent role for inhibitory mechanisms in the visual processing of the upper cortical layers. Our findings share similarities with recent experimental studies focusing on the opposing influence of top-down and bottom-up inputs in the mouse primary visual cortex during visual flow perturbations.


Subject(s)
Visual Cortex , Mice , Animals , Visual Cortex/physiology , Photic Stimulation , Neurons/physiology , Sensation , Visual Perception/physiology
11.
Healthcare (Basel) ; 12(5)2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38470699

ABSTRACT

Age-related differences in physical activity (PA), maturity status (PHV), physical performance (PP), and academic achievement (AA) among schoolchildren in Qatar were examined. Sixty-nine students from a school in Doha were categorized into three equal (n = 23) groups: 11-year-old students (U11; male: n = 14), 12-year-old students (U12: male: n = 7), and 13-year-old students (U13: male: n = 11). The testing process comprised a medicine ball throw, Stork balance test, hand grip strength test, the T-half test (PP), GPA in Arabic, mathematics, science (AA), International Physical Activity Questionnaire Short Form (PA), and Moore's equations (PHV). Relevant age-related differences (p < 0.001) were identified in mathematics, science, the T-half test, maturity, and arm span. Notably, differences between adjacent age groups were evident between U11 and U12, concerning arm span, maturity, mathematics, and science, and between U12 and U13 (the T-half test, mathematics, science). Concerning AP, the performance maxima were calculated for U12 (mathematics, science) and U11 (Arabic). Regarding PP, performance maxima were only observed for U13. Except for the moderate level, the highest levels of PA were detected in U13. Maturity status and anthropometric parameters did not differ significantly between age groups. However, AA demonstrated the most notable age-related differences. Specifically, mathematics showed substantial differences between adjacent age groups.

12.
J Chem Ecol ; 50(3-4): 143-151, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38366062

ABSTRACT

Chemical repellents play a crucial role in personal protection, serving as essential elements in reducing the transmission of vector-borne diseases. A biorational perspective that extends beyond the olfactory system as the classical target may be a promising direction to move. The taste system provides reliable information regarding food quality, helping animals to discriminate between nutritious and potentially harmful food sources, often associated with a bitter taste. Understanding how bitter compounds affect feeding in blood-sucking insects could unveil novel molecules with the potential to reduce biting and feeding. Here, we investigated the impact of two naturally occurring bitter compounds, caffeine and quinine, on the feeding decisions in female Aedes aegypti mosquitoes at two distinctive phases: (1) when the mosquito explores the biting substrate using external taste sensors and (2) when the mosquito takes a sip of food and tastes it using internal taste receptors. We assessed the aversiveness of bitter compounds through both an artificial feeding condition (artificial feeder test) and a real host (arm-in-cage test). Our findings revealed different sensitivities in the external and internal sensory pathways responsible for detecting bitter taste in Ae. aegypti. Internal detectors exhibited responsiveness to lower doses compared to the external sensors. Quinine exerted a more pronounced negative impact on biting and feeding activity than caffeine. The implications of our findings are discussed in the context of mosquito food recognition and the potential practical implications for personal protection.


Subject(s)
Aedes , Caffeine , Feeding Behavior , Quinine , Taste , Animals , Female , Caffeine/pharmacology , Aedes/physiology , Feeding Behavior/drug effects
13.
J Clin Med ; 13(4)2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38398370

ABSTRACT

Background: The relationship between physical activity (PA), health-related physical performance (PP), and academic achievement (AA) plays an important role in childhood. This study examined the differences in PA, sedentary behavior, health-related PP, maturity status, and AA between normal-weight and obese school children in Qatar. Methods: Eighty schoolchildren were recruited (age: 12.1 ± 0.6 years). Based on age-specific BMI percentiles, the children were classified as normal weight (n = 40) or obese (n = 40). Moore's equations were used to estimate their maturity status (PHV). The measurements encompassed anthropometric data as well as PP tests (medicine ball throw, postural stability, handgrip strength). AA was assessed by reviewing school records for grade point average in Mathematics, Science, and Arabic courses. The total amount of time spent participating in PA each week was calculated using the International Physical Activity Questionnaire Short Form. Results: Handgrip strength was the only parameter that showed a relevant group difference (p < 0.001, ηp2 = 0.15; normal weight: 19.7 ± 3.46 N; obese: 21.7 ± 2.80 N). We found only one moderate correlation between PHV and handgrip strength (r = 0.59). Conclusions: The findings suggest that obesity status alone might not serve as a sufficient predictor of AA in school or PA levels.

14.
Insects ; 15(2)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38392518

ABSTRACT

Immature mosquitoes are thought to breathe only atmospheric air through their siphons despite reports of prolonged submerged survival. We studied the survival of last-instar larvae of Aedes aegypti fully submerged at different temperatures and measured the oxygen consumption from air and water-dissolved larvae and pupae of this species under different conditions. Larvae survived much longer than expected, reaching 50% mortality only after 58, 10, and 5 days at 15°, 25°, and 35 °C, respectively. Larval to pupa molt was only observed in larvae with access to air, whereas individuals kept submerged never molted. Although most of the oxygen was obtained from the air, larvae obtained 12.72% of their oxygen from the water, while pupae took only 5.32%. In both media, temperature affected the respiration rate of the larvae, with relatively close Q10 values (1.56 and 1.83 for water and air, respectively). A similar pattern of O2 consumption was observed in Ae. albopictus, whose larvae obtained 12.14% of their oxygen from the water. The detailed quantification of oxygen consumption by mosquito larvae showed that water-dissolved oxygen is not negligible and physiologically relevant, challenging the idea that mosquito larvae only breathe atmospheric oxygen.

15.
Adv Exp Med Biol ; 1443: 1-22, 2024.
Article in English | MEDLINE | ID: mdl-38409413

ABSTRACT

Extracellular vesicles (EVs) are bilayer membrane particles released from several cell types to the extracellular environment. EVs have a crucial role in cell-cell communication, involving different biological processes in health and diseases. Due to the potential of biomarkers for several diseases as diagnostic and therapeutic tools, it is relevant to understand the biology of the EVs and their content. One of the current challenges involving EVs is regarding the purification method, which is a critical step for EV's functional and characterization studies. Ultracentrifugation is the most used method for EV isolation, where the nanoparticles are separated in sequential centrifugation to isolate the EVs based on their size. However, for viscous biofluids such as plasma, there is a co-isolation of the most abundant proteins, which can impair the EV's protein identification due to the low abundance of these proteins and signal suppression by the most abundant plasma proteins. Emerging techniques have gained attention in recent years. Titanium dioxide (TiO2) is one of the most promising techniques due to its property for selective isolation based on the interaction with phospholipids in the EV membrane. Using a small amount of TiO2 beads and a low volume of plasma, it is possible to isolate EVs with reduced plasma protein co-isolation. This study describes a comprehensive workflow for the isolation and characterization of plasma extracellular vesicles (EVs) using mass spectrometry-based proteomics techniques. The aim of this chapter is describe the EV isolation using TiO2 beads enrichment and high-throughput mass spectrometry techniques to efficiently identify the protein composition of EVs in a fast and straightforward manner.


Subject(s)
Extracellular Vesicles , Titanium , Microspheres , Extracellular Vesicles/metabolism , Blood Proteins/analysis , Blood Proteins/metabolism , Plasma
16.
IEEE Trans Image Process ; 33: 671-681, 2024.
Article in English | MEDLINE | ID: mdl-38190671

ABSTRACT

Oriented object detection is a challenging and relatively new problem. Most existing approaches are based on deep learning and explore Oriented Bounding Boxes (OBBs) to represent the objects. They are typically based on adaptations of traditional detectors that work with Horizontal Bounding Boxes (HBBs), which have been exploring IoU-like loss functions to regress the HBBs. However, extending this idea for OBBs is challenging due to complex formulations or requirement for customized backpropagation implementations. Furthermore, using OBBs presents limitations for irregular or roughly circular objects, since the definition of the ideal OBB is an ambiguous and ill-posed problem. In this work, we jointly tackle the problem of training, representing, and evaluating oriented detectors. We explore Gaussian distributions-called Gaussian Bounding Boxes (GBBs)-as fuzzy representations for oriented objects and propose using a similarity metric between two GBBs based on the Hellinger distance. We show that this metric leads to a differentiable closed-form expression that can be directly used as a localization loss term to train OBB object detectors. We also show that GBBs present a natural representation as elliptical regions (called EBBs), which inherently mitigate ambiguity representation for circular objects. Finally, we empirically show that the proposed similarity metric computed between two GBBs strongly correlates with the IoU between the corresponding EBBs, motivating the name Probabilistic Intersection-over-Union (ProbIoU). Our experiments show that results using ProbIoU as a regression loss are competitive with state-of-the-art alternatives without requiring additional hyperparameters or customized implementations, and that ProbIoU is a promising alternative to evaluate oriented object detectors. Our code is available at https://github.com/ProbIOU/.

17.
Nat Commun ; 15(1): 275, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38177131

ABSTRACT

Targeted protein degradation (TPD) mediates protein level through small molecule induced redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal degradation. TPD has recently emerged as a key modality in drug discovery. So far only a few ligases have been utilized for TPD. Interestingly, the workhorse ligase CRBN has been observed to be downregulated in settings of resistance to immunomodulatory inhibitory drugs (IMiDs). Here we show that the essential E3 ligase receptor DCAF1 can be harnessed for TPD utilizing a selective, non-covalent DCAF1 binder. We confirm that this binder can be functionalized into an efficient DCAF1-BRD9 PROTAC. Chemical and genetic rescue experiments validate specific degradation via the CRL4DCAF1 E3 ligase. Additionally, a dasatinib-based DCAF1 PROTAC successfully degrades cytosolic and membrane-bound tyrosine kinases. A potent and selective DCAF1-BTK-PROTAC (DBt-10) degrades BTK in cells with acquired resistance to CRBN-BTK-PROTACs while the DCAF1-BRD9 PROTAC (DBr-1) provides an alternative strategy to tackle intrinsic resistance to VHL-degrader, highlighting DCAF1-PROTACS as a promising strategy to overcome ligase mediated resistance in clinical settings.


Subject(s)
Carrier Proteins , Proteolysis Targeting Chimera , Ubiquitin-Protein Ligases , Carrier Proteins/metabolism , Proteolysis , Ubiquitin/metabolism , Ubiquitin-Protein Ligases/metabolism
18.
J Sports Med Phys Fitness ; 64(1): 45-54, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37800402

ABSTRACT

BACKGROUND: This study aimed to compare the effects of block periodized training and training adapted to the menstrual cycle (MC) phases on endurance performance, cardiovascular parameters, recovery, and MC-related symptoms in active females. METHODS: Fourteen naturally menstruating, moderately trained females (age: 24±3 years; BMI: 22.3±2.7) were randomized into an intervention (INT) and a control (CON) group. Throughout an 8-week intervention period, both groups participated in a polarized training program. In the INT, the training sessions were adapted to the MC with higher training loads within the mid and late follicular phase. Before and after the intervention maximal oxygen consumption (VO2max), velocity and heart rate at ventilatory thresholds one and two (vVT1, vVT2, hrVT1, hrVT2), systolic and diastolic blood pressure (sBP, dBP), root mean square of successive RR interval differences (RMSSD), standard deviation of NN intervals (SDNN), pulse wave velocity (PWV), and the premenstrual assessment form (PAF) were assessed. RESULTS: There were no significant time × group interaction effects in all physiological parameters (VO2max: P=0.890; vVT1: P=1.000; hrVT1: P=0.464; vVT2: P=0.356; hrVT2: P=0.762 sBP: P=0.948; dBP: P=0.203; RMSSD: P=0.257; SDNN: P=0.241; PWV: P=0.818), or psychological parameters (PAF: P=0.745). CONCLUSIONS: Tailoring a polarized training program to the MC did not augment training responses compared to a regular training program in active females. However, a substantial portion of the training intervention in the CON was coincidentally matched to the MC.


Subject(s)
Physical Endurance , Pulse Wave Analysis , Female , Humans , Young Adult , Adult , Physical Endurance/physiology , Menstrual Cycle/physiology , Oxygen Consumption/physiology , Heart Rate/physiology
19.
Nat Prod Res ; 38(6): 978-985, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37154616

ABSTRACT

Investigation of the endophytic fungi Nigrospora sphaerica, Nigrospora oryzae, and Pseudofusicoccum stromaticum MeOH fractions isolated from the leaves of Vochysia divergens, a medicinal species from the Brazilian Pantanal, led to the identification of five compounds, namely a new compound (1E,8Z)-10,11-dihydroxy-5,5,8-trimethyl-4-oxocycloundeca-1,8-diene-1-carbaldehyde (1) and four known compounds: 5-methylmellein (2), sclerone (3), daldinone A (4), and lasiodiplodin (5). All compounds were identified using spectroscopic methods, and 1 was corroborated with mass spectrometry, while the known compounds were compared with data in the literature. The relative configuration of compound 1 was determined based on theoretical conformational studies as well as the J experimental values between the hydroxymethyne hydrogens. The antimicrobial activity of the compounds was evaluated. Promising results were obtained for compounds 2, 4, and 5 since they inhibited the bacterium Pseudomonas aeruginosa, an opportunistic pathogen, suggesting the potential of these microorganisms as a source of new antibacterial agents.


Subject(s)
Anti-Infective Agents , Anti-Infective Agents/chemistry , Fungi/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolism , Plant Leaves/microbiology , Brazil , Endophytes/metabolism
20.
Eur J Appl Physiol ; 124(5): 1535-1545, 2024 May.
Article in English | MEDLINE | ID: mdl-38157043

ABSTRACT

PURPOSE: Self-myofascial release (SMR) is a form of self-massage aiming to release tension, improve blood flow, and alleviate muscle soreness. This study aimed to determine whether a single session of SMR could impact cardiovascular parameters at rest and during a cold pressor test (CPT). METHODS: Twenty male participants (aged 26 ± 2 years) underwent a 20-min SMR and a 20-min seated control condition (CON) on two separate test days in a randomized order. Peripheral and central blood pressure (BP), total peripheral resistance (TPR), pulse wave velocity (PWV), heart rate (HR), root mean square of successive RR interval differences (RMSSD), and the quotient of low-frequency power and high-frequency power (LF/HF) were measured both at rest and during a CPT before (t0), 2 min (t1), and 20 min (t2) after the SMR and CON. RESULTS: Time × condition interactions could be detected for peripheral and central diastolic BP, TPR, HR, and RMSSD. Following the SMR, peripheral diastolic BP, central diastolic BP, TPR, and RMSSD were reduced, while HR was increased compared to the CON. Regarding the CPT time × condition interactions could be detected for peripheral, and central diastolic BP, with lower values after SMR. CONCLUSION: The results of the present study suggest that a single bout of SMR confers favorable cardiovascular benefits in healthy normotensive individuals. Furthermore, SMR can attenuate the hemodynamic reactivity to a stress test. Future research should address whether regular SMR leads to chronic adaptations similar to regular, moderate aerobic exercise, massage therapy, and static stretching.


Subject(s)
Autonomic Nervous System , Heart Rate , Hemodynamics , Massage , Humans , Male , Adult , Autonomic Nervous System/physiology , Hemodynamics/physiology , Heart Rate/physiology , Massage/methods , Blood Pressure/physiology , Rest/physiology , Heart/physiology
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