Restricted Interval Research Articles

High-Intensity Interval Training, Caloric Restriction, or Their Combination Have Beneficial Effects on Metabolically Acquired Peripheral Neuropathy.

Peripheral neuropathy (PN) is a prevalent and debilitating complication of obesity, prediabetes, and type 2 diabetes, which remains poorly understood and lacks disease-modifying therapies. Fortunately, diet and/or exercise have emerged as effective treatment strategies for PN. Here, we examined the impact of caloric restriction (CR) and high-intensity interval training (HIIT) interventions, alone or combined (HIIT-CR), on metabolic and PN outcomes in high-fat diet (HFD) mice. HFD feeding alone resulted in obesity, impaired glucose tolerance, and PN. Peripheral nerves isolated from these mice also developed insulin resistance (IR). CR and HIITCR, but not HIIT alone, improved HFD-induced metabolic dysfunction. However, all interventions improved PN to similar extents. When examining the underlying neuroprotective mechanisms in whole nerve, we found that CR and HIIT-CR activate the fuel-sensing enzyme AMP-activated protein kinase (AMPK). We then performed complimentary in vitro work in Schwann cells, the glia of peripheral nerve. Treating primary Schwann cells with the saturated fatty acid palmitate to mimic prediabetic conditions caused IR, which was reversed by the AMPK activator, AICAR. Together, these results enhance our understanding of PN pathogenesis, the differential mechanisms by which diet and exercise may improve PN, and Schwann cell-specific contributions to nerve insulin signaling and PN progression.

EXPERIENCES OF EXCLUSIVE BREASTFEEDING AMONG EMPLOYED MOTHERS AT PT. HEINZ ABC IN THE YEAR 2023

Background: One contributing factor to the failure of breastfeeding is the rising prevalence of mothers engaged in full-time employment, exemplified by occupations like factory work. This phenomenon is attributed to various impediments, including restricted intervals for rest, inadequacy of workplace amenities and provisions, and the presence of fatigue. Objective: To comprehensively understand the breastfeeding endeavors of mothers employed at PT Heinz ABC factory, delving into their experiences is imperative. Methods: Qualitative The research employed a generic qualitative research approach, utilizing purposive sampling as the sampling technique. The research involved nine informants who were mothers employed in factories and had children aged between 7-24 months. Data collection was conducted through online in-depth interviews conducted via WhatsApp voice calls. The researchers also employed supportive instruments, specifically interview guides that had undergone pilot interviews beforehand. The data analysis was conducted through thematic analysis. Results: This research is segmented into three themes, namely knowledge, self-efficacy, and barriers. Conclusion: The prevalence of breastfeeding practices among mothers employed in factories remains low. This can be attributed to obstacles hindering the sustained implementation of exclusive breastfeeding, including inadequacies in workplace facilities, restricted rest intervals, psychological pressure, and low self-efficacy.

PbMgNbO3 dielectric aging in the freezing temperature region

Aging of the relaxors and PbMgNbO3 in particular was extensively studied in last two decades. Most of the results were related to the low temperature glass-like region. No systematic data around the freezing temperatures were reported. To cover this still missing information we have studied the evolution of the dielectric spectra in the broad frequency region from 10−1 Hz to 106 Hz both below and above the freezing temperature 240 K. Below freezing temperature the existence of the earlier reported waiting time–frequency scaling at frequencies below ≈50 Hz is confirmed. At higher frequencies this deviation from the scaling is observed that can be tentatively attributed to the complexity of the relaxing entities. Above Tf aging is observed only in the restricted frequency interval below the maximum of the dielectric loss spectrum. The observed effect can be attributed to the hardening and narrowing of the dielectric loss spectra and decreasing of the dielectric strength with time. The explanation is proposed based on the concept of the creation of the degenerate polar nanoregions covering several chemically ordered regions (COR) (multi PNRs—MPNRs). These MPNRs are large compare to the PNRs located at the single CORs and some of them may become frozen resulting in the described spectra changes.

Trace element compositions and geochronology of cassiterite from the Bushveld Large Igneous Province, South Africa

This study presents trace element compositions and ages of four representative cassiterite samples from the Zaaiplaats, Union and Rooiberg Sn fields, all spatially associated with the Bushveld Large Igneous Province (LIP), South Africa. The Zaaiplaats Sn field is endogranitic and entirely hosted within the variably-altered Bobbejaankop and Lease granites of the Lebowa Granite Suite. In contrast, the exogranitic Union and Rooiberg Sn fields occur within the Union Tin Member of the Rooiberg Group, and the Pretoria Group of the Transvaal Supergroup, respectively. Collectively, all the cassiterite samples display quasi-parallel chondrite-normalised rare earth element (REE) patterns characterised by relative enrichments in the heavy REE, and yielded ages varying within a relatively restricted interval between 2061 ± 40 Ma and 2054 ± 3 Ma. This age range compares well with those reported from the Bushveld LIP and, when combined with mineral compositions, suggests a common granitic source for cassiterites from all the Sn fields. The exogranitic Rooiberg and Union Sn fields are identified by cassiterites with Zr/Hf of ∼40, whereas the endogranitic Zaaiplaats Sn field is characterised by cassiterites enriched in most incompatible elements (e.g., Nb, Ta, Zr, Hf, In, F and B) and Zr/Hf of ∼10. These Zr/Hf ratios agree with the endogranitic and exogranitic Sn ores from other localities, but are different from the very low Zr/Hf ratios of ∼3 reported for endogranitic cassiterites associated with rare-metal granites. The Zr versus Hf discrimination diagram may therefore be useful for distinguishing the endogranitic and exogranitic origins of cassiterites and for identifying the extent of fractionation of the causative source.

Trace elements and organic geochemical fingerprinting of natural crude oils from the Monterey Formation, offshore Santa Maria Basin, California

Based on our recent analytical method development using microwave digestion and triple-quad ICP-MS, we have analyzed up to 57 elements for 20 natural crude oil samples from the offshore Santa Maria Basin of California, a prolific producing basin thought to be sourced dominantly from the Monterey Formation. Our goal is mainly to see if there were oil-oil correlations between wells (fractured reservoir mixing) or no correlation (locally sourced from an unconventional restricted depth reservoir or compartment), and which part (upper and/or lower) of the Monterey Formation acted as the primary source of oil. The results show distinct fingerprints based on V/Mo and Ni/Mo ratios derived from each of the wells where the oils were sampled during stem tests, indicating that they might be partially correlated with restricted intervals of the stratigraphy (or lithofacies). The V/Mo and Ni/Mo ratios of the oils also show that the lower Phosphatic-carbonate lithofacies of Monterey Formation may be a primary source of the oils. Vanadium and Ni contents, V/(Ni + V) ratios, and sulfur content of the oils indicate that the Monterey Formation was deposited under reducing marine conditions. The linear correlation between Mg and Ca contents and non-linear correlation between P and Ca contents in the oil samples may indicate that dolomite-rich rather than apatite-rich portions of Monterey Formation may be a critical source rock component. The similarity between REY distribution patterns of the oils and authigenic carbonate implies that carbonates might have been correlated with formation of the oils. Positive Eu anomalies in most oils reveal possible hydrothermal influences associated with magmatic and slab window effects as a consequence of the Farallon-Pacific Ridge subduction, higher heat flow, and later transtensional and transpressional deformation during deposition of Monterey Formation. The comparable REY distribution patterns for the oils and outcrop shales of Lions Head reveal potential oil-source correlations.

Evaluating bubble chain phenomena as a mechanism for open system degassing in basaltic systems

Passive degassing – i.e., the open-system degassing of a magmatic gas phase that is decoupled from the melt phase – is common at many basaltic volcanic systems and consistently makes a greater contribution to total volcanic gas emissions than eruptive degassing. However, the mechanism for passive degassing is not fully understood. We investigate the feasibility of permeable gas flow through connected bubbles or pathways using experiments with aqueous solutions of hydroxyethyl cellulose (HEC), a non-Newtonian analogue material for magma. Stable chains of connected bubbles have previously been reported in similar non-Newtonian polymer solutions. We observe a range of bubble chain phenomena and identified five regimes, numbering in order of increasing gas flow rate: 1) small individual bubbles; 2) chains of rounded bubbles; 3) chains of elongate bubbles; 4) pipe-like ‘winding flue’; 5) large individual bubbles. The bubble chain phenomena (regimes 2–4) are observed over a restricted interval of gas flow rates. We determine the rheology of the solutions and conclude that the HEC solutions that produced bubble chain phenomena in our experiments are well scaled to shear-thinning and viscoelastic magmas, hence bubble chain phenomena could form in magmas. Our analysis also suggests that the viscoelastic rheology of HEC plays a fundamental role in the observed bubble chain phenomena.

Ex vivo comparative investigation of suprachiasmatic nucleus excitotoxic resiliency

Background: Glutamate signaling in the brain is regulated by release, reuptake, and receptor responsiveness. In diseased conditions, glutamate signaling can exceed normal regulatory processes, giving rise to a condition called excitotoxicity. Although regional differences in the excitotoxic effects of glutamate in the brain have been reported, the extent and characteristics of these potential differences are not clear. Here we compared the excitotoxic resiliency of the suprachiasmatic nucleus (SCN), anterior hypothalamus (AH) and cortex. Methods: We treated acute brain slices containing either the SCN and AH or the cortex from adult male mice at different times across the diurnal cycle with varying concentrations of N-methyl-D-aspartate (NMDA), NMDA+ α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or control medium. The extent of cell damage was assessed using propidium iodide (PI), a cell death marker. Results: The results indicate that all three brain regions exhibited increasing cell damage/death when treated with increasing concentrations of NMDA. However, higher concentrations of NMDA were needed to significantly increase cell damage in the SCN compared to the cortex and AH. All three brain regions also exhibited greater cell death/damage when treated in the nighttime compared to the daytime, although the SCN exhibited increased cell death during a more restricted time interval compared to the AH and cortex. Conclusions: Together, these data confirm previous studies showing excitotoxic resiliency in the SCN, while extending them in two ways. First, we demonstrate a dose-dependency in excitotoxic susceptibility that differentiates the SCN from the surrounding AH and the cortex using a brain slice preparation. Second, we demonstrate a diurnal rhythm in excitotoxic susceptibility with a broadly similar phase across all three brain regions. These data increase our understanding of the extent and nature of the SCN excitotoxic resiliency, which will inform future studies on the cellular mechanisms underlying this phenomenon.

Farmer-centered pesticide risk reduction education in Senegal: A novel, participatory approach

As pest pressures continue to intensify across Sub-Saharan Africa, many smallholder farmers are increasing their use of pesticides, including highly hazardous options, to meet the market demands for high-quality fresh produce. Many of these farmers, however, have not had access to pesticide risk reduction training or have participated in programs that have not enabled them to protect themselves and their families. Given the risks posed by dried and invisible though still toxic pesticide residues, new forms of information and realistic learning strategies are required. This study combined the innovative Adaptive Learner-Centered Education (ALCE) approach with the Farmer Field School (FFS) model to address the need for a rigorous pesticide risk reduction program. This hybrid method was piloted over two years in a project with smallholder farmers in the Niayes region of Senegal. The findings demonstrate that following a 12-week course, this novel approach enabled 20 farmer-facilitators to educate and train 236 other farmers to reduce their use of highly hazardous pesticides, select pesticides with shorter restricted re-entry intervals, and adopt protective mitigation practices. Through seasonal planning exercises, farmers operationalized new knowledge in ways that fit their crop production needs and protected themselves and their families. Because the ALCE-FFS process is grounded in community-based needs, it can serve as an appropriate educational design framework for practitioners working in a wide range of geographic, sociocultural, and political contexts.

Ex vivo comparative investigation of suprachiasmatic nucleus excitotoxic resiliency

Background: Glutamate signaling in the brain is regulated by release, reuptake, and receptor responsiveness. In diseased conditions, glutamate signaling can exceed normal regulatory processes, giving rise to a condition called excitotoxicity. Although regional differences in the excitotoxic effects of glutamate in the brain have been reported, the extent and characteristics of these potential differences are not clear. Here we compared the excitotoxic resiliency of the suprachiasmatic nucleus (SCN), anterior hypothalamus (AH) and cortex. Methods: We treated acute brain slices containing either the SCN and AH or the cortex from adult male mice at different times across the diurnal cycle with varying concentrations of N-methyl-D-aspartate (NMDA), NMDA+ α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or control medium. The extent of cell damage was assessed using propidium iodide (PI), a cell death marker. Results: The results indicate that all three brain regions exhibited increasing cell damage/death when treated with increasing concentrations of NMDA. However, higher concentrations of NMDA were needed to significantly increase cell damage in the SCN compared to the cortex and AH. All three brain regions also exhibited greater cell death/damage when treated in the nighttime compared to the daytime, although the SCN exhibited increased cell death during a more restricted time interval compared to the AH and cortex. Conclusions: Together, these data confirm previous studies showing excitotoxic resiliency in the SCN, while extending them in two ways. First, we demonstrate a dose-dependency in excitotoxic susceptibility that differentiates the SCN from the surrounding AH and the cortex using a brain slice preparation. Second, we demonstrate a diurnal rhythm in excitotoxic susceptibility with a broadly similar phase across all three brain regions. These data increase our understanding of the extent and nature of the SCN excitotoxic resiliency, which will inform future studies on the cellular mechanisms underlying this phenomenon.

Strong solvability of restricted interval systems and its applications in quadratic and geometric programming

We consider interval systems of linear equations and inequalities with a restriction to some a priori given set. We focus on a characterization of strong solvability, that is, solvability for each realization of interval values, and we compare this with an existence of a strong solution defined analogously. The motivation comes from the area of interval-valued optimization problems, where strong solvability means guaranteed feasibility of any realization of the problem. Strong solvability with strict inequalities implies the robust Slater condition, which ensures that standard optimality conditions can be used. We apply the issues particularly in two optimization classes, convex quadratic programming with quadratic constraints and posynomial geometric programming. For the former, we also utilize the presented result to improve a characterization of the worst case optimal value. Eventually, we state several open problems that emerged while deriving the results.

Evolution of the COVID-19 pandemic in Italy at the national and regional levels from February 2020 to March 2022

<abstract> <p>The COVID-19 pandemic initially hit Italy at the end of February 2020. In the following two years, there were about 13 million diagnosed cases and more than 150000 deaths. For this period, we have performed a study that evaluates and compares the impacts on public health of the SARS-CoV-2 waves at the national and regional levels. Based on contagion trends, we considered four pandemic waves. For each wave, we also analyzed a restricted time interval of one month around the peak. We found an underestimation of diagnosed cases and a saturation of available intensive care unit (ICU) beds during the first wave. The second wave had a more significant impact on public health, highlighting that the system of physical distancing measures was less effective than the lockdown implemented during the first wave. Instead, during the first three peaks, the incidence of ICU bed occupancy was superimposable. In general, odds ratios of case fatality rate showed a more significant risk for males than females from the age of thirty onwards. We verified that regional responses to the health emergency were not homogeneous. In particular, in contrast with the national temporal trend, some regions showed a significant increase in the incidence of deaths. Furthermore, we found positive correlations between availability and occupancy of hospital beds from the second wave onward. In contrast, a significant correlation was verified for ICU bed occupancy and deaths only during the second peak. In light of what happened, it would be desirable to plan an increase in public health funds for new emergencies and issue a rigorous plan to face pandemics.</p> </abstract>

Ex vivo comparative investigation of suprachiasmatic nucleus excitotoxic resiliency

Background: Glutamate signaling in the brain is regulated by release, reuptake, and receptor responsiveness. In diseased conditions, glutamate signaling can exceed normal regulatory processes, giving rise to a condition called excitotoxicity. Although regional differences in the excitotoxic effects of glutamate in the brain have been reported, the extent and characteristics of these potential differences are not clear. Here we compared the excitotoxic resiliency of the suprachiasmatic nucleus (SCN), anterior hypothalamus (AH) and cortex. Methods: We treated acute brain slices containing either the SCN and AH or the cortex from adult male mice at different times across the diurnal cycle with varying concentrations of N-methyl-D-aspartate (NMDA), NMDA+ α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or control medium. The extent of cell damage was assessed using propidium iodide (PI), a cell death marker. Results: The results indicate that all three brain regions exhibited increasing cell damage/death when treated with increasing concentrations of NMDA. However, higher concentrations of NMDA were needed to significantly increase cell damage in the SCN compared to the cortex and AH. All three brain regions also exhibited greater cell death/damage when treated in the nighttime compared to the daytime, although the SCN exhibited increased cell death during a more restricted time interval compared to the AH and cortex. Conclusions: Together, these data confirm previous studies showing excitotoxic resiliency in the SCN, while extending them in two ways. First, we demonstrate a dose-dependency in excitotoxic susceptibility that differentiates the SCN from the surrounding AH and the cortex using a brain slice preparation. Second, we demonstrate a diurnal rhythm in excitotoxic susceptibility with a broadly similar phase across all three brain regions. These data increase our understanding of the extent and nature of the SCN excitotoxic resiliency, which will inform future studies on the cellular mechanisms underlying this phenomenon.

Fractional Lau effect with binary gratings: A frequency analysis

A theoretical study of the fractional Lau effect is performed for a Lau set-up equipped with binary gratings. The separations between the two gratings are chosen equal to an elementary distance divided by a positive integer. Fourier components of the observed pattern function are calculated for these distances. Also, this study shows that it is sufficient to study the Lau patterns in a restricted interval of the gratings separation. Experimental and simulation results are consistent with the theoretical predictions.

CBLRR: a cauchy-based bounded constraint low-rank representation method to cluster single-cell RNA-seq data.

The rapid development of single-cel+l RNA sequencing (scRNA-seq) technology provides unprecedented opportunities for exploring biological phenomena at the single-cell level. The discovery of cell types is one of the major applications for researchers to explore the heterogeneity of cells. Some computational methods have been proposed to solve the problem of scRNA-seq data clustering. However, the unavoidable technical noise and notorious dropouts also reduce the accuracy of clustering methods. Here, we propose the cauchy-based bounded constraint low-rank representation (CBLRR), which is a low-rank representation-based method by introducing cauchy loss function (CLF) and bounded nuclear norm regulation, aiming to alleviate the above issue. Specifically, as an effective loss function, the CLF is proven to enhance the robustness of the identification of cell types. Then, we adopt the bounded constraint to ensure the entry values of single-cell data within the restricted interval. Finally, the performance of CBLRR is evaluated on 15 scRNA-seq datasets, and compared with other state-of-the-art methods. The experimental results demonstrate that CBLRR performs accurately and robustly on clustering scRNA-seq data. Furthermore, CBLRR is an effective tool to cluster cells, and provides great potential for downstream analysis of single-cell data. The source code of CBLRR is available online at https://github.com/Ginnay/CBLRR.

Medical Countermeasure Requirements to Meet NASA's Space Radiation Permissible Exposure Limits for a Mars Mission Scenario.

The space radiation environment consists of a complex mixture of ionizing particles that pose significant health risks to crew members. NASA currently requires that an astronaut's career Risk of Exposure Induced Death (REID) for cancer mortality should not exceed 3% at the upper 95% confidence level. This career radiation limit is likely to be exceeded for even the shortest round-trip mission scenario to Mars. As such, NASA has begun to pursue more vigorously approaches to directly reduce radiation risks, despite the large uncertainties associated with such projections. A recent study considered cohort studies of aspirin and warfarin as possible medical countermeasures (MCMs) acting to reduce background cancer mortality rates used in astronaut risk projections. It was shown that such MCMs can reduce the REID for specific tissues in restricted time intervals over which the drugs were administered; however, the cumulative effect on total lifetime REID was minimal. As an extension, the present work addresses more general MCM requirements that would be needed to meet current NASA radiation limits for a Mars mission scenario. A sensitivity analysis is performed within the major components of the NASA cancer risk model that would likely be modified by MCM interventions. This includes the background cancer incidence and mortality rates, epidemiologically based hazard rates derived from acute terrestrial exposures, and radiation quality factors used to translate terrestrial exposures to space radiation. Relationships between possible MCMs and each of these components are discussed. Results from this study provide important information regarding MCM requirements needed to meet NASA limits for planned Mars missions. Insight into the types of countermeasures expected to yield greatest reductions in crew risk is also gained.

The combination of intermittent caloric restriction and moderate-intensity interval training in decreasing blood glucose and CRP levels with a high glycemic index diet

This study aims to analyze the effect of the combination of intermittent calorie restriction and moderate intensity interval training (MIIT) on serum c-reactive protein (CRP) levels as one of the inflammatory mediators and blood glucose levels in female mice exposed to a-high glycemic index diet. The sample of this study was female mice Balb/c strain, divided into four groups:, the control group (con), the intermittent calorie restriction group (restrict), the MIIT group (interv), and the combine group of intermittent calorie restriction and moderate-intensity interval training (restrict+interv). A high glycemic index diet was a high calorie and was provided by standard feed and oral gavage of 0.013 g/gBW glucosesolution. Intermittent calorie restriction was 50% reduction of the standard feed 3x/week. The MIIT was five-minute intervals of swimming and 30 seconds of passive rest consecutively for 30 minutes and 3x/week. Meanwhile, the treatment duration was four weeks. The oral glucose tolerance test consisting of fasting blood glucose (FBG) and a two-hour post -prandial (2HPP) blood glucose was measured before and after the treatment. CRP was examined only after the treatment. The restrict + interv group had a significant reduction in CRP levels compared to the restricted group (p = 0.005) and the interv group (p = 0.044). The FBG levels the restrict + interv group and restricted group had a significant decrease (p = 0.026). Moreover, 2HPP of the restrict + interv group and restricted group had a significant decline (p = 0.000). This study concludes that the combination of intermittent calorie restriction and moderate -intensity interval training can attenuate elevated serum CRP and blood glucose levels.

Simple phasor-based deep neural network for fluorescence lifetime imaging microscopy

Fluorescence lifetime imaging microscopy (FLIM) is a powerful technique to probe the molecular environment of fluorophores. The analysis of FLIM images is usually performed with time consuming fitting methods. For accelerating this analysis, sophisticated deep learning architectures based on convolutional neural networks have been developed for restrained lifetime ranges but they require long training time. In this work, we present a simple neural network formed only with fully connected layers able to analyze fluorescence lifetime images. It is based on the reduction of high dimensional fluorescence intensity temporal decays into four parameters which are the phasor coordinates, the mean and amplitude-weighted lifetimes. This network called Phasor-Net has been applied for a time domain FLIM system excited with an 80 MHz laser repetition frequency, with negligible jitter and afterpulsing. Due to the restricted time interval of 12.5 ns, the training range of the lifetimes was limited between 0.2 and 3.0 ns; and the total photon number was lower than 106, as encountered in live cell imaging. From simulated biexponential decays, we demonstrate that Phasor-Net is more precise and less biased than standard fitting methods. We demonstrate also that this simple architecture gives almost comparable performance than those obtained from more sophisticated networks but with a faster training process (15 min instead of 30 min). We finally apply successfully our method to determine biexponential decays parameters for FLIM experiments in living cells expressing EGFP linked to mCherry and fused to a plasma membrane protein.

Slices of Hewitt–Stromberg measures and co-dimensions formula

Abstract This paper studies the behavior of the lower and upper multifractal Hewitt–Stromberg functions under slices onto ( n - m ) {(n-m)} -dimensional subspaces. More precisely, we discuss the relationship between the multifractal Hewitt–Stromberg functions of a compactly supported Borel probability measure and those of slices or sections of the measure. In addition, we prove that if μ has a finite m-energy and q lies in a certain somewhat restricted interval, then these functions satisfy the expected adding of co-dimensions formula.

A successive convex optimization method for bilinear matrix inequality problems and its application to static output‐feedback control

AbstractThis article explores a successive convex optimization method for solving a class of nonconvex programming problems subject to bilinear matrix inequality (BMI) constraints. In particular, many control issues can be boiled down to BMI problems, which are typically NP‐hard. To get out of the predicament, we propose a more relaxed feasible set to approximate the original one, based on which a local optimization algorithm is developed and its convergence is analyzed. As a case of application, we consider static output‐feedback control for uncertain systems with disturbances in restricted frequency intervals. In order to strengthen the disturbance‐rejection capability over the given frequency range, we establish sufficient and necessary analysis conditions via the generalized Kalman‐Yakubovich‐Popov lemma, under which the homogeneous polynomially parameter‐dependent technique is adopted to facilitate the design. Finally, several examples are given to demonstrate the efficiency of the results.

An approach for enforcing a class of GMECs on time Petri nets with uncontrollable transitions

Real-time control is of great significance for practical plants such as intelligent manufacturing systems and transportation systems, and timing information should be integrated in their discrete models. The existing specifications expressed by generalized mutual exclusion constraints (GMECs) do not consider timing specifications in the control design of these models, which would be restrictive for the control specifications of a timed system. In the framework of time Petri net (TPN) models, this paper introduces a class of GMECs, called time GMECs (TGMECs), in which each GMEC is associated with a restricted time interval. By restricting the firing intervals of controllable transitions, an efficient method based on control functions is proposed to implement TGMECs on a TPN system in presence of uncontrollable transitions. The core of the reported method is to employ the transitions-related timing constraints in a partial modified state class graph (PMSCG) to solve mathematical programming problems. Such a PMSCG is a graph recently introduced to enhance the supervisor permissiveness for a TPN system with GMECs. In particular, the terminal condition for the construction of a PMSCG is modified. By taking advantage of the PMSCG, an online control procedure is presented to implement the supervision for TGMECs in a maximally permissive way.