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Rationale: Plasma cell-free DNA levels correlate with disease severity in many conditions. Pretransplant cell-free DNA may risk stratify lung transplant candidates for post-transplant complications. Objectives: To evaluate if pretransplant cell-free DNA levels and tissue sources identify patients at high risk of primary graft dysfunction and other pre- and post-transplant outcomes. Methods: This multicenter, prospective cohort study recruited 186 lung transplant candidates. Pretransplant plasma samples were collected to measure cell-free DNA. Bisulfite sequencing was performed to identify the tissue sources of cell-free DNA. Multivariable regression models determined the association between cell-free DNA levels and the primary outcome of primary graft dysfunction and other transplant outcomes, including Lung Allocation Score, chronic lung allograft dysfunction, and death. Measurements and Main Results: Transplant candidates had twofold greater cell-free DNA levels than healthy control patients (median [interquartile range], 23.7 ng/ml [15.1-35.6] vs. 12.9 ng/ml [9.9-18.4]; P < 0.0001), primarily originating from inflammatory innate immune cells. Cell-free DNA levels and tissue sources differed by native lung disease category and correlated with the Lung Allocation Score (P < 0.001). High pretransplant cell-free DNA increased the risk of primary graft dysfunction (odds ratio, 1.60; 95% confidence interval [CI], 1.09-2.46; P = 0.0220), and death (hazard ratio, 1.43; 95% CI, 1.07-1.92; P = 0.0171) but not chronic lung allograft dysfunction (hazard ratio, 1.37; 95% CI, 0.97-1.94; P = 0.0767). Conclusions: Lung transplant candidates demonstrate a heightened degree of tissue injury with elevated cell-free DNA, primarily originating from innate immune cells. Pretransplant plasma cell-free DNA levels predict post-transplant complications.
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Ácidos Nucleicos Livres , Transplante de Pulmão , Disfunção Primária do Enxerto , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Gravidade do PacienteRESUMO
OBJECTIVE: This study investigated the effects of nondriving-related task (NDRT) touchscreen location and NDRT difficulty level on the driver task performance, eye gaze behavior, and workload during SAE Level 3 conditionally automated driving. Two driver tasks were considered: a visuomanual NDRT and a take-over task. BACKGROUND: Touchscreens are expected to play important roles inside automated vehicles. However, few studies have investigated the driver-touchscreen interaction during automated driving. METHOD: A driving simulator experiment was conducted. The experimental task consisted of two successive subtasks: an NDRT followed by a take-over task. NDRT touchscreen location (Upper Left, Upper Right, and Lower Right) and NDRT difficulty level (Easy and Hard) were the independent variables. A set of driver task performance, eye gaze behavior, and perceived workload measures were employed for each subtask as the dependent variables. RESULTS: NDRT touchscreen location significantly affected both the NDRT and the take-over task performance. Lower Right was superior to Upper Right in the NDRT performance but was inferior in the take-over task performance. NDRT touchscreen location affected the perceived physical workload of the NDRT. NDRT difficulty level affected the perceived workload of the take-over task. CONCLUSION: The research findings enhance our understanding of how NDRT touchscreen location and NDRT difficulty level impact the driver task performance during conditionally automated driving, and, further provide useful design implications and knowledge. APPLICATION: The study results would inform the NDRT touchscreen interface design and the NDRT design for conditionally automated vehicles.
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Excited-state aromatization dynamics in the photochemical ring opening of dihydroazulene (DHA) is investigated by nonadiabatic molecular dynamics simulations in connection with the mixed-reference spin-flip (MRSF)-TDDFT method. It is found that, in the main reaction channel, the ring opening occurs in the excited state in a sequence of steps with increasing aromaticity. The first stage lasting ca. 200 fs produces an 8π semiaromatic S1 minimum (S1, min) through an ultrafast damped bond length alternation (BLA) movement synchronized with a partial planarization of the cycloheptatriene ring. An additional ca. 200 fs are required to gain the vibrational energy needed to overcome a ring-opening transition state characterized by an enhanced Baird aromaticity. Unlike other BLA motions of ππ* state, it was shown that their damping is a characteristic feature of aromatic bond-equalization process. In addition, some minor channels of the reaction have also been discovered, where noticeably higher barriers of the S1 non/antiaromatic transition structures must be surmounted. These anti-Baird channels led to reformation of DHA or other closed-ring products. The observed competition between the Baird and anti-Baird channels suggests that the quantum yield of photochemical products can be controllable by tipping their balance. Hence, here we suggest including the concept of anti-Baird, which would expand the applicability of Baird rule to much broader situations.
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We demonstrate an InGaZnO (IGZO)-based synaptic transistor with a TiO2buffer layer. The structure of the synaptic transistor with TiO2inserted between the Ti metal electrode and an IGZO semiconductor channel O2trapping layer produces a large hysteresis window, which is crucial for achieving synaptic functionality. The Ti/TiO2/IGZO synaptic transistor exhibits reliable synaptic plasticity features such as excitatory post-synaptic current, paired-pulse facilitation, and potentiation and depression, originating from the reversible charge trapping and detrapping in the TiO2layer. Finally, the pattern recognition accuracy of Modified National Institute of Standards and Technology handwritten digit images was modeled using CrossSim simulation software. The simulation results present a high image recognition accuracy of â¼89%. Therefore, this simple approach using an oxide buffer layer can aid the implementation of high-performance synaptic devices for neuromorphic computing systems.
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The accurate description of solvent effects on X-ray absorption spectra (XAS) is fundamental for comparing the simulated spectra with experiments in solution. Currently, few protocols exist that can efficiently reproduce the effects of the solute/solvent interactions on XAS. Here, we develop an efficient and accurate theoretical protocol for simulating the solvent effects on XAS. The protocol combines electrostatic embedding QM/MM based on electrostatic potential fitted operators for describing the solute/solvent interactions and mixed-reference spin-flip time-dependent density functional theory (MRSF-TDDFT) for simulating accurate XAS spectra. To demonstrate the capabilities of our protocol, we compute the X-ray absorption of neutral proline in the gas phase and ionic proline in water in all relevant K-edges, showing excellent agreement with experiments. We show that states represented by core to π* transitions are almost unaffected by the interaction with water, whereas the core to σ* transitions are more impacted by the fluctuation of proline structure and the electrostatic interaction with the solvent. Finally, we reconstruct the pH-dependent XAS of proline in solution, determining that the N K-edge can be used to distinguish its three protonation states.
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This study investigated possible backpack weight effects on the performance of three basic short-term/working memory (STM/WM) tasks conducted concurrently with the physical task of route walking. The STM/WM tasks were the Corsi block-tapping, digit span, and 3-back tasks, and, were employed to examine the visuo-spatial sketchpad, phonological loop and central executive components of the WM system. Four backpack weight levels (0%, 15%, 25% and 40% of body mass) were considered. Thirty participants conducted the three experimental tasks requiring physical-cognitive multitasking. Data analyses revealed that: (1) increased backpack weight resulted in decreases in the performance of the Corsi block-tapping and the 3-back task, but (2) backpack weight did not significantly affect the digit span task performance. The study results suggest that reducing backpack weight could benefit the performance of various cognitive tasks during route walking. The study findings may be useful for the ergonomics design of body-worn equipment and human-system interfaces.Practitioner summary: This study examined the backpack weight effects on the performance of three basic short-term/working memory tasks conducted concurrently with the physical task of route walking. The study revealed that reducing backpack weight could benefit various cognitive tasks during physical-cognitive multitasking, especially cognitive tasks that require visuospatial processing and executive control.
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Memória de Curto Prazo , Caminhada , Humanos , ErgonomiaRESUMO
The reliable conductance modulation of synaptic devices is key when implementing high-performance neuromorphic systems. Herein, we propose a floating gate indium gallium zinc oxide (IGZO) synaptic device with an aluminum trapping layer to investigate the correlation between its diverse electrical parameters and pattern recognition accuracy. Basic synaptic properties such as excitatory postsynaptic current, paired pulse facilitation, long/short term memory, and long-term potentiation/depression are demonstrated in the IGZO synaptic transistor. The effects of pulse tuning conditions associated with the pulse voltage magnitude, interval, duration, and cycling number of the applied pulses on the conductance update are systematically investigated. It is discovered that both the nonlinearity of the conductance update and cycle-to-cycle variation should be critically considered using an artificial neural network simulator to ensure the high pattern recognition accuracy of Modified National Institute of Standards and Technology (MNIST) handwritten digit images. The highest recognition rate of the MNIST handwritten dataset is 94.06% for the most optimized pulse condition. Finally, a systematic study regarding the synaptic parameters must be performed to optimize the developed synapse device.
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The reliable conductance modulation of synaptic devices is key when implementing high-performance neuromorphic systems. Herein, we propose a floating gate IGZO synaptic device with an aluminum trapping layer to investigate the correlation between its diverse electrical parameters and pattern recognition accuracy. Basic synaptic properties such as excitatory postsynaptic current, paired pulse facilitation, long/short term memory, and long-term potentiation/depression are demonstrated in the IGZO synaptic transistor. The effects of pulse tuning conditions associated with the pulse voltage magnitude, interval, duration, and cycling number of the applied pulses on the conductance update are systematically investigated. It is discovered that both the nonlinearity of the conductance update and cycle-to-cycle variation should be critically considered using an artificial neural network simulator to ensure the high pattern recognition accuracy of Modified National Institute of Standards and Technology (MNIST) handwritten digit images. The highest recognition rate of the MNIST handwritten dataset is 94.06% for the most optimized pulse condition. Finally, a systematic study regarding the synaptic parameters must be performed to optimize the developed synapse device.
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This study investigated how sex modifies postural discomfort perception during a sagittally-symmetric, seated static posture holding (SPH) task. Ten male and 10 female participants performed SPH and conducted subjective discomfort ratings in a total of 108 task conditions. A regression analysis found that the impacts of the body joint reactive moments on perceived discomfort were larger for the female group than the male whereas that of the shoulder joint angle was more pronounced for the male than the female. Also, some of the 108 task conditions were found to be more uncomfortable for the male group, while some others, for the female. The observed sex impacts are thought to be due to the sex differences in physical work capacities (muscular strength and joint flexibility). The results suggest that new posture analysis tools allowing sex-specific analyses are needed as they would improve the accuracy and precision of ergonomics posture analyses. Practitioner summary: This study empirically investigated how sex modifies postural discomfort perception during a seated posture holding (SPH) task. Sex was found to modify the impacts of joint reactive moments and the shoulder joint angle. The study results seem to reflect the sex differences in muscular strength and joint flexibility.
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Postura , Caracteres Sexuais , Feminino , Masculino , Humanos , Ergonomia , Postura Sentada , Amplitude de Movimento ArticularRESUMO
OBJECTIVE: A driving simulator study was conducted to comparatively evaluate the effects of three camera monitor system (CMS) display layouts and the traditional side-view mirror arrangement on the physical demands of driving. BACKGROUND: Despite the possible benefits of CMS displays in reducing the physical demands of driving, little empirical evidence is available to substantiate these benefits. The effects of CMS display layout designs are not well understood. METHOD: The three CMS display layouts varied in the locations of the side-view displays: (A) inside the car near the conventional side-view mirrors, (B) on the dashboard at each side of the steering wheel, and (C) on the center fascia with the displays joined side by side. Twenty-two participants performed a safety-critical lane changing task with each design alternative. The dependent measures were the following: spread of eye movement, spread of head movement, and perceived physical demand. RESULTS: Compared with the traditional mirror system, all three CMS display layouts showed a reduction in physical demands, albeit differing in the types/magnitudes of physical demand reduction. CONCLUSION: Well-designed CMS display layouts could significantly reduce the physical demands of driving. The physical demands were reduced by placing the CMS displays close to the position of the driver's normal line-of-sight when looking at the road ahead and locating each CMS display on each side of the driver, that is, at locations compatible with the driver's expectation. APPLICATION: Physical demand reductions by CMS displays would especially benefit drivers frequently checking the side-view mirrors with large eye/head movements and physically weak/impaired drivers.
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Condução de Veículo , Simulação por Computador , Movimentos Oculares , Humanos , Exame FísicoRESUMO
Various heart diseases cause cardiac remodeling, which in turn leads to ineffective contraction. Although it is an adaptive response to injury, cardiac fibrosis contributes to this remodeling, for which the reactivation of quiescent myofibroblasts is a key feature. In the present study, we investigated the role of the p300/CBP-associated factor (PCAF), a histone acetyltransferase, in the activation of cardiac fibroblasts. An intraperitoneal (i.p.) injection of a high dose (160 mg/kg) of isoproterenol (ISP) induced cardiac fibrosis and reduced the amount of the PCAF in cardiac fibroblasts in the mouse heart. However, the PCAF activity was significantly increased in cardiac fibroblasts, but not in cardiomyocytes, obtained from ISP-administered mice. An in vitro study using human cardiac fibroblast cells recapitulated the in vivo results; an treatment with transforming growth factor-ß1 (TGF-ß1) reduced the PCAF, whereas it activated the PCAF in the fibroblasts. PCAF siRNA attenuated the TGF-ß1-induced increase in and translocation of fibrosis marker proteins. PCAF siRNA blocked TGF-ß1-mediated gel contraction and cell migration. The PCAF directly interacted with and acetylated mothers against decapentaplegic homolog 2 (SMAD2). PCAF siRNA prevented TGF-ß1-induced phosphorylation and the nuclear localization of SMAD2. These results suggest that the increase in PCAF activity during cardiac fibrosis may participate in SMAD2 acetylation and thereby in its activation.
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Fibroblastos/metabolismo , Miocárdio/citologia , Proteína Smad2/metabolismo , Fatores de Transcrição de p300-CBP/metabolismo , Acetilação , Actinas/metabolismo , Animais , Movimento Celular , Núcleo Celular/metabolismo , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Fibrose , Humanos , Isoproterenol , Masculino , Metaloproteinases da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Fosforilação , Transporte Proteico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fatores de Transcrição de p300-CBP/genéticaRESUMO
This study examined obesity impacts on task performance and perceived discomfort during seated foot target reaches. Three independent variables, participant group, movement distance, and, movement direction, were considered. The task performance measures employed were reaction time, movement time and task performance time. Perceived discomfort was measured using a modified Borg CR-10 scale. Statistical analyses revealed that: obesity was associated with increases in movement time, reaction time and performance time; movement distance significantly affected the three task performance measures and discomfort rating; and, movement direction significantly affected movement time, performance time and discomfort rating. The obesity impacts observed are thought to reflect the decelerating effects of the extra fat mass in the obese body during foot reaches and possibly obesity-related physiological and cognitive changes. Design improvements of foot-operated systems, such as reducing distances to targets, increasing target sizes and avoiding forward foot reaches, may help counteract the observed obesity impacts. Practitioner Summary: This study empirically investigated the obesity impacts on task performance and perceived discomfort during seated foot target reaches. Obesity was found to be associated with increases in movement time, reaction time and performance time. The observed obesity impacts seem attributable to the anthropometric, motor and cognitive characteristics of the obese.Abbreviations: ANOVA: analysis of variance; BMI: body mass index; ROM: range of motion; Borg CR-10: Borg's category ratio 10 scale.
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Obesidade , Análise e Desempenho de Tarefas , Índice de Massa Corporal , Pé , Humanos , Amplitude de Movimento ArticularRESUMO
Fumarylacetoacetate hydrolase (FAH) superfamily proteins are found ubiquitously in microbial pathways involved in the catabolism of aromatic substances. Although extensive bioinformatic data on these proteins have been acquired, confusion caused by problems with the annotation of these proteins hinders research into determining their physiological functions. Here we classify 606 FAH superfamily proteins using a maximum likelihood (ML) phylogenetic tree, comparative gene-neighbourhood patterns and in vitro enzyme assays. The FAH superfamily proteins used for the analyses are divided into five distinct subfamilies, and two of them, FPH-A and FPH-B, contain the majority of the proteins of undefined function. These subfamilies include clusters designated FPH-I and FPH-II, respectively, which include two distinct types of fumarylpyruvate hydrolase (FPH), an enzyme involved in the final step of the gentisate pathway. We determined the crystal structures of these FPH enzymes at 2.0 Å resolutions and investigate the substrate binding mode by which these types of enzymes can accommodate fumarylpyruvate as a substrate. Consequentially, we identify the molecular signatures of the two types of FPH enzymes among the broadly conserved FAH superfamily proteins. Our studies allowed us to predict the relationship of unknown FAH superfamily proteins using their sequence information.
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Proteínas de Bactérias/química , Proteínas de Bactérias/classificação , Hidrolases/química , Hidrolases/classificação , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Hidrolases/genética , Hidrolases/metabolismo , FilogeniaRESUMO
Bacillus cereus ATCC 14579 is a known polyhydroxybutyrate (PHB)-producing microorganism that possesses genes associated with PHB synthesis such as PhaA, PhaB, and PHA synthases. PhaA (i.e., thiolase) is the first enzyme in the PHA biosynthetic pathway, which catalyze the condensation of two acetyl-CoA molecules to acetoacetyl-CoA. Our study elucidated the crystal structure of PhaA in Bacillus cereus ATCC 14579 (BcTHL) in its apo- and CoA-bound forms. BcTHL adopts a type II biosynthetic thiolase structure by forming a tetramer. The crystal structure of CoA-complexed BcTHL revealed that the substrate binding site of BcTHL is constituted by different residues compared with other known thiolases. Our study also revealed that Arg221, a residue involved in ADP binding, undergoes a positional conformational change upon the binding of the CoA molecule.
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Acetil-CoA C-Acetiltransferase/química , Bacillus cereus/enzimologia , Proteínas de Bactérias/química , Domínio Catalítico , Coenzima A/química , Cristalografia por Raios X , Hidroxibutiratos/metabolismo , Modelos MolecularesRESUMO
A technique for directly growing two-dimensional (2D) materials onto conventional semiconductor substrates, enabling high-throughput and large-area capability, is required to realise competitive 2D transition metal dichalcogenide devices. A reactive sputtering method based on H2S gas molecules and sequential in situ post-annealing treatment in the same chamber was proposed to compensate for the relatively deficient sulfur atoms in the sputtering of MoS2 and then applied to a 2D MoS2/p-Si heterojunction photodevice. X-ray photoelectron, Raman, and UV-visible spectroscopy analysis of the as-deposited Ar/H2S MoS2 film were performed, indicating that the stoichiometry and quality of the as-deposited MoS2 can be further improved compared with the Ar-only MoS2 sputtering method. For example, Ar/H2S MoS2 photodiode has lower defect densities than that of Ar MoS2. We also determined that the factors affecting photodetector performance can be optimised in the 8-12 nm deposited thickness range.
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We present optical characterization, calibration, and performance tests of the Mesospheric Airglow/Aerosol Tomography Spectroscopy (MATS) satellite, which for the first time, to the best of our knowledge, for a satellite, applies a linear-astigmatism-free confocal off-axis reflective optical design. Mechanical tolerances of the telescope were investigated using Monte Carlo methods and single-element perturbations. The sensitivity analysis results indicate that tilt errors of the tertiary mirror and a surface RMS error of the secondary mirror mainly degrade optical performance. From the Monte Carlo simulation, the tolerance limits were calculated to ±0.5mm, ±1mm, and ±0.15∘ for decenter, despace, and tilt, respectively. We performed characterization measurements and optical tests with the flight model of the satellite. Multi-channel relative pointing, total optical system throughput, and distortion of each channel were characterized for end-users. Optical performance was evaluated by measuring the modulation transfer function (MTF) and point spread function (PSF). The final MTF performance was 0.25 MTF at 20 lp/mm for the ultraviolet channel (304.5 nm), and 0.25-0.54 MTF at 10 lp/mm for infrared channels. The salient fact of the PSF measurement of this system is that there is no noticeable linear astigmatism detected over a wide field of view (5.67∘×0.91∘). All things considered, the design method showed great advantages in wide field of view observations with satellite-level optical performance.
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Transition-metal-catalyzed activation of C-H and C-C bonds is a challenging area in synthetic organic chemistry. Among various methods to accomplish these processes, the approach using metal-organic cooperative catalytic systems is one of the most promising. In this protocol, organic molecules as well as transition metals act as catalysts to bring about reactions, which proceed with high efficiencies and selectivities. Various metal-organic cooperative catalytic systems developed for C-H and C-C bond activation reactions are discussed in this review. Also discussed are how each metal-organic cooperative catalyst affects the reaction mechanism and what kinds of substrates can be applied in each of the catalytic processes.
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In this study, we demonstrate a transistor-type ZnO nanowire (NW) memory device based on the surface defect states of a rough ZnO NW, which is obtained by introducing facile H2O2 solution treatment. The surface defect states of the ZnO NW are validated by photoluminescence characterisation. A memory device based on the rough ZnO NW exhibits clearly separated bi-stable states (ON and OFF states). A significant current fluctuation does not exist during repetitive endurance cycling test. Stable memory retention characteristics are also achieved at a high temperature of 85 °C and at room temperature. The surface-treated ZnO NW device also exhibits dynamically well-responsive pulse switching under a sequential pulse test configuration, thereby indicating its potential practical memory applications. The simple chemical treatment strategy can be widely used for modulating the surface states of diverse low-dimensional materials.
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We present the development of a compact f/7.3 (D=35 mm) three-mirror reflective telescope for the atmospheric-research microsatellite Mesospheric Airglow/Aerosol Tomography Spectroscopy (MATS). The telescope design was driven by the end users' need for a reflective wide-field (5.67°×0.91°) optic with high stray light rejection and six detection channels with separate image sensors, operating at wavelengths 270-772 nm. For the first time, a design method for wide-field off-axis telescopes-in which linear astigmatism is eliminated-was applied and tested in practice. Single-point diamond turning was used to produce two sets of 37-110 mm large free-form aluminum mirrors with surface figure errors and roughness values of 34-62 nm (RMS)/193-497 nm (PV) and 2.8-3.5 nm (RMS), respectively. A method that combines precise machining and geometry measurements (using a coordinate measuring machine) was employed to fabricate an aluminum structure to accurately position the mirrors without the need for manual alignment. The telescope was tested with a network of plate beamsplitters and filters, which define the spectral selection for the six detection channels. Imaging performance measurements were carried out using a reflective off-axis collimator, which projects imaging targets at infinite focus. A modulation transfer function (MTF) value of 0.45 at 20 lp/mm was measured at â¼760 nm (diffraction limit: 0.85) using a slanted edge target. By modeling the measured mirror surfaces in optical design software, a reoptimization of the mirror positions could be performed and an improved MTF of â¼0.75 at 20 lp/mm was predicted. The results demonstrate design- and building methods that can be utilized to make off-axis telescopes for a vast range of applications.
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This study empirically investigated the effects of backpack weight on the performance of three basic short-term/working memory (STM/WM) tasks during flat-surface standing. Four levels of backpack weight were considered: 0, 15, 25 and 40% of the body weight. The three STM/WM tasks were the Corsi block, digit span and 3-back tasks, corresponding to the visuo-spatial sketchpad, phonological loop and central executive of WM, respectively. Thirty participants conducted the STM/WM tasks while standing with loaded backpack. Major study findings were that (1) increased backpack weight adversely affected the scores of all three STM/WM tasks; and, (2) the adverse effect of backpack weight was less pronounced for the phonological loop STM task than the other STM/WM tasks. The study findings may help understand and predict the impacts of body-worn equipment weight on the worker's mental task performance for various work activities requiring simultaneous performance of mental and physical tasks. Practitioner summary: The current study empirically examined the effects of backpack weight on the performance of three basic STM/WM tasks. The study findings entail that reduces the weight of body-worn equipment can positively impact the worker's mental task performance in addition to reducing the worker's bodily stresses. Abbreviations: ACC: anterior cingulate cortex; AP: anterior-posterior; BW: body weight; CoP: centre of pressure; C-S: central executive working memory task and standing; DLPFC: dorsolateral prefrontal cortex; HIP: human information processing; ML: medio-lateral; PMC: premotor cortex; P-S: phonological loop short-term memory task and standing; SMA: supplementary motor area; STM: short-term memory; VLPFC: ventrolateral prefrontal cortex; V-S: visuo-spatial short-term memory task and standing; WM: working memory.