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With the focus on the insufficient origin-based cold storage in China, this study investigates the location and routing problem (LRP) of origin-based cold storage for fresh agricultural products. This study considers the loss of fresh agricultural products in different environments during transportation and presents a cold storage LRP model. To address this issue, a hybrid whale algorithm with heuristic rules is designed, and the effectiveness of the algorithm is verified by standard instances. Finally, taking Chenggu County as a practical case, the influence of cold storage capacity and farmers' demand for refrigeration are analysed. Experimental results show that the proposed algorithm has a good effect in solving medium-scale LRP. As the storage capacity increases, the total cost of the system can be increased by 0.086%. As farmers' demand for refrigeration increases, the total cost of the system can be increased by 34.034%. Farmers' demand has a greater impact on the system's total costs than the cold storage capacity. When optimizing the cold storage layout, changes in fresh agricultural product output in the next few years can be roughly predicted, and the most economical optimization scheme can be obtained. [ABSTRACT FROM AUTHOR]

Abstract With the focus on the insufficient origin-based cold storage in China, this study investigates the location and routing problem (LRP) of origin-based cold storage for fresh agricultural products. This study considers the loss of fresh agricultural products in different environments during transportation and presents a cold storage LRP model. To address this issue, a hybrid whale algorithm with heuristic rules is designed, and the effectiveness of the algorithm is verified by standard instances. Finally, taking Chenggu County as a practical case, the influence of cold storage capacity and farmers’ demand for refrigeration are analysed. Experimental results show that the proposed algorithm has a good effect in solving medium-scale LRP. As the storage capacity increases, the total cost of the system can be increased by 0.086%. As farmers’ demand for refrigeration increases, the total cost of the system can be increased by 34.034%. Farmers’ demand has a greater impact on the system’s total costs than the cold storage capacity. When optimizing the cold storage layout, changes in fresh agricultural product output in the next few years can be roughly predicted, and the most economical optimization scheme can be obtained.

Telomerase activity is directly affected by the laminin receptor precursor (LRP) protein, a highly conserved nonintegrin transmembrane receptor, which has been shown to have therapeutic effects in ageing, and age‐related diseases. Recently, it has been found that overexpression of LRP‐FLAG, by plasmid transfection, leads to a significant increase in telomerase activity in cell culture models. This may indicate that upregulation of LRP can be used to treat various age‐related diseases. However, transfection is not a viable treatment strategy for patients. Therefore, we present a nanoencapsulated protein‐based drug synthesised using poly(lactic‐co‐glycolic acid) (PLGA) nanocapsules for delivery of the 37 kDa LRP protein therapeutic. PLGA nanocapsules were synthesised using the double emulsification‐solvent evaporation technique. Different purification methods, including filtration and centrifugation, were tested to ensure that the nanocapsules were within the optimal size range, and the BCA assay was used to determine encapsulation efficiency. The completed drug was tested in a HEK‐293 cell culture model, to investigate the effect on cell viability, LRP protein levels and telomerase activity. A significant increase in total LRP protein levels with a concomitant increase in cell viability and telomerase activity was observed. Due to the observed increase in telomerase activity, this approach could represent a safer alternative to plasmid transfection for the treatment of age‐related diseases.

Telomerase activity is directly affected by the laminin receptor precursor (LRP) protein, a highly conserved nonintegrin transmembrane receptor, which has been shown to have therapeutic effects in ageing, and age‐related diseases. Recently, it has been found that overexpression of LRP‐FLAG, by plasmid transfection, leads to a significant increase in telomerase activity in cell culture models. This may indicate that upregulation of LRP can be used to treat various age‐related diseases. However, transfection is not a viable treatment strategy for patients. Therefore, we present a nanoencapsulated protein‐based drug synthesised using poly(lactic‐co‐glycolic acid) (PLGA) nanocapsules for delivery of the 37 kDa LRP protein therapeutic. PLGA nanocapsules were synthesised using the double emulsification‐solvent evaporation technique. Different purification methods, including filtration and centrifugation, were tested to ensure that the nanocapsules were within the optimal size range, and the BCA assay was used to determine encapsulation efficiency. The completed drug was tested in a HEK‐293 cell culture model, to investigate the effect on cell viability, LRP protein levels and telomerase activity. A significant increase in total LRP protein levels with a concomitant increase in cell viability and telomerase activity was observed. Due to the observed increase in telomerase activity, this approach could represent a safer alternative to plasmid transfection for the treatment of age‐related diseases. [ABSTRACT FROM AUTHOR]

Aims There is little information on the regulation of cholesterol homeostasis in the brain. Whether cholesterol crosses the blood–brain barrier is under investigation, but the present understanding is that cholesterol metabolism in the brain is independent from that in peripheral tissues. Lipoprotein receptors from the LDL receptor family (LRPs) have key roles in lipid particle accumulation in cells involved in vascular and cardiac pathophysiology; however, their function on neural cells is unknown. Methods and results The expression of LRP5 and the components and targets of its downstream signalling pathway, the canonical Wnt pathway, including β-catenin, LEF1, VEGF, OPN, MMP7, and ADAM10, is analysed in the brains of Wt and Lrp5−/− mice and in a neuroblastoma cell line. LRP5 expression is increased in a time- and dose-dependent manner after lipid loading in neuronal cells; however, it does not participate in cholesterol homeostasis as shown by intracellular lipid accumulation analyses. Neurons challenged with staurosporin and H2O2 display an anti-apoptotic protective role for LRP5. Conclusions For the first time, it has been shown that neurons can accumulate intracellular lipids and lipid uptake is performed mainly by the LDLR, while CD36, LRP1, and LRP5 do not play a major role. In addition, it has been shown that LRP5 triggers the canonical Wnt pathway in neuronal cells to generate pro-survival signals. Finally, Lrp5−/− mice have maintained expression of LRP5 only in the brain supporting the biological plausible concept of the need of brain LRP5 to elicit pro-survival processes and embryonic viability. [ABSTRACT FROM AUTHOR]

Robots are becoming increasingly sophisticated in the execution of complex tasks. However, an area that requires development is the ability to act in dynamically changing environments. To advance this, developments have turned towards understanding the human brain and applying this to improve robotics. The present study used electroencephalogram (EEG) data recorded from 54 human participants whilst they performed a two-choice task. A build-up of motor activity starting around 400 ms before response onset, also known as the lateralized readiness potential (LRP), was observed. This indicates that actions are not simply binary processes but rather, response-preparation is gradual and occurs in a temporal window that can interact with the environment. In parallel, a robot arm executing a pick-and-place task was developed. The understanding from the EEG data and the robot arm were integrated into the final system, which included cell assemblies (CAs)—a simulated spiking neural network—to inform the robot to place the object left or right. Results showed that the neural data from the robot simulation were largely consistent with the human data. This neurorobotics study provides an example of how to integrate human brain recordings with simulated neural networks in order to drive a robot. [ABSTRACT FROM AUTHOR]

The contextual cueing effect is the phenomenon observed when response time (RT) becomes faster in visual search in repeated context compared with a new one. In the present study, we explored whether the mechanisms involved in the effect are age dependent. We investigated it in younger (N = 20, 12 women, 21.2 ± 1.75 years) and older (N = 19, nine women, 67.05 ± 3.94 years) adults. We found a faster target identification in the repeated configurations with similar magnitude in the two age groups, which indicates that this contextual cueing effect remained intact even in the older participants. To shed light on the underlying mechanisms, we measured and compared the amplitude of three event‐related potentials: N2pc, P3, and response‐locked LRP. In the younger group, the larger contextual cueing effect (novel‐minus‐repeated RT difference) correlated positively with a larger difference in amplitude for repeated compared with novel configurations for both the N2pc and the P3 components, but there was no correlation with the response‐locked lateralized readiness potential (rLRP) amplitude difference. However, in the older group, only the rLRP amplitude difference between novel and repeated configurations showed an enhancement with larger contextual cueing. These results suggest that different mechanisms are responsible for the contextual effect in the two age groups. It has both an early and an intermediate locus in younger adults: effective attentional allocation and successful stimulus categorization, or decision‐making confidence are involved; while in older adults, a late locus was identified: a more efficient response organization led to a faster reaction. In our study, we show that younger and older adults rely on different mechanisms when using contextual information to improve performance in a visual search task. Finding a target in repeated spatial configurations compared with new ones (contextual cueing effect) was equally faster in both age groups, which was a consequence of more efficient attention allocation and stimuli identification in younger and more efficient inhibition of distractor stimuli and response organization in older adults. [ABSTRACT FROM AUTHOR]

Two independent experiments were performed with three groups each (sepsis control, sepsis, and sepsis with apoE23 treatment) to investigate the anti-inflammatory effect of apolipoprotein 23 (apoE23) in a mouse model of sepsis induced by S. typhimurium. Survival rates; plasma level variations in tumor necrosis factor (TNF)-α, interleukin (IL)-6, and lipopolysaccharide (LPS); S. typhimurium colony-forming units in the spleen tissue; and mRNA and protein expression levels of low-density lipoprotein receptor (LDLR), LDLR-related protein (LRP), syndecan-1, and scavenger receptor B1 were evaluated in the livers of mice from the three groups. Results found that the survival rate of septic mice treated with apoE23 was 100% within 48 h, while it was only 40% in septic mice without apoE23 treatment (P < 0.001). The plasma LPS, TNF-α, and IL-6 levels and the S. typhimurium load in mice in the apoE23-treated group were significantly lower than those in septic mice (P < 0.05). Moreover, apoE23 restored the downregulated expression of LDLR and LRP in the liver tissue of septic mice. So apoE23 exhibits an anti-inflammatory effect in the mouse model of S. typhimurium-induced sepsis. Further studies are required to understand the mechanisms underlying the anti-inflammatory effects of apoE23.

Systemic toxicity is a major challenge in the development of therapeutics. Consequently, cell-type-specific targeting is needed to improve on-target efficacy while reducing off-target toxicity. Here, we describe a cell-targeting system we have termed BRAID (BRidged Activation by Intra/intermolecular Division) whereby an active molecule is divided into two inactive or less active parts that are subsequently brought together via a so-called ‘bridging receptor’ on the target cell. This concept was validated using the WNT/β-catenin signaling system, demonstrating that a multivalent WNT agonist molecule divided into two inactive components assembled from different epitopes via the hepatocyte receptor βKlotho induces signaling specifically on hepatocytes. These data provide proof of concept for this cell-specific targeting strategy, and in principle, this may also allow activation of multiple signaling pathways where desirable. This approach has broad application potential for other receptor systems.

Multidrug resistance (MDR) is the cell resistance to a number of drugs. Proteins from the ABC-transporter family are the most studied factors of the MDR phenomenon. According to the literature Pgp, MRP1, BCRP, and LRP are proteins involved in the development of the MDR. The authors detected the expression of these proteins in untreated patients with acute myeloid leukemia (other than M3). Expression of these proteins was observed in 64.3%, 46.4%, 64.3%, and 42.9% of patients, respectively. In all non-responders blast cells expressed more than one marker of MDR. Expression of 3 and 4 markers was found in 80% of non-responders while in responders 1—2 markers were expressed in 83%.

Previous studies have analyzed the efficacy of near-infrared spectroscopy-derived lipid core burden index (LCBI) in quantifying and identifying high-risk plaques and patients at increased risk of future major adverse cardiac outcomes/major adverse cardiovascular and cerebrovascular events. A maxLCBI 4mm of 400 or greater seems to be an effective threshold for classifying at-risk plaques. This meta-analysis provides a more precise odds ratio with a narrow standard deviation that can be used to guide future studies. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to compare cortical motor planning activity during response selection and motor execution processes between individuals with anterior cruciate ligament reconstruction (ACLR) and uninjured controls during a reaction time and response selection task. Methods: Individuals with ACLR (n = 20) and controls (n = 20) performed a lateralized choice reaction time (e.g., Go/NoGo) task. Electrocortical activity and reaction time were recorded concurrently using electroencephalography and inertial measurement units. Separate stimulus locked and response-locked event-related potentials were computed for each limb. The lateralized readiness potential (LRP) was computed as the interhemispheric differences between waveforms and the mean LRP area and onset latency were recorded. Active motor threshold was determined using transcranial magnetic stimulation. Differences between groups (ACLR vs control) and limbs (involved vs uninvolved) and the associations between LRP characteristics and response performance (number of errors) were assessed. Results: Participants with ACLR have had smaller LRP area during periods of response selection (P = 0.043, d = 0.4) and motor execution (P = 0.015, d = 0.5) and committed more errors in both Go (P < 0.001, d = 0.8) and NoGo (P = 0.032, d = 0.5) response conditions. There were no differences in latency of response selection or motor execution. Participants with ACLR had higher active motor thresholds (P < 0.001, d = 1.3) than controls, which was weakly associated with smaller LRP areas (r = 0.32–0.42, P < 0.05). Conclusions: The ACLR group demonstrated greater motor planning and response inhibition during a choice reaction time task. More errant performance also suggests poorer decision making in the presence of a "speed-accuracy" trade-off. Key features of the sample, including lower corticospinal excitability, lend support to an interpretation of widespread cortical inhibition contributing to impairments in response selection and motor execution. [ABSTRACT FROM AUTHOR]

Motivated by the recent literature that finds that artificial neural networks (NN) can efficiently predict economic time‐series in general and inflation in particular, we investigate if the forecasting performance can be improved even further by using a particular kind of NN—a recurrent neural network. We use a long short‐term memory recurrent neural network (LSTM) that was proven to be highly efficient for sequential data and computed univariate forecasts of monthly US CPI inflation. We show that even though LSTM slightly outperforms autoregressive model (AR), NN, and Markov‐switching models, its performance is on par with the seasonal autoregressive model SARIMA. Additionally, we conduct a sensitivity analysis with respect to hyperparameters and provide a qualitative interpretation of what the networks learn by applying a novel layer‐wise relevance propagation technique. [ABSTRACT FROM AUTHOR]

Robots are becoming increasingly sophisticated in the execution of complex tasks. However, an area that requires development is the ability to act in dynamically changing environments. To advance this, developments have turned towards understanding the human brain and applying this to improve robotics. The present study used electroencephalogram (EEG) data recorded from 54 human participants whilst they performed a two-choice task. A build-up of motor activity starting around 400 ms before response onset, also known as the lateralized readiness potential (LRP), was observed. This indicates that actions are not simply binary processes but rather, response-preparation is gradual and occurs in a temporal window that can interact with the environment. In parallel, a robot arm executing a pick-and-place task was developed. The understanding from the EEG data and the robot arm were integrated into the final system, which included cell assemblies (CAs)—a simulated spiking neural network—to inform the robot to place the object left or right. Results showed that the neural data from the robot simulation were largely consistent with the human data. This neurorobotics study provides an example of how to integrate human brain recordings with simulated neural networks in order to drive a robot.

ABSTRACT Feast-famine response proteins are a widely conserved class of global regulators in prokaryotes, the most highly studied of which is the Escherichia coli leucine-responsive regulatory protein (Lrp). Lrp senses the environmental nutrition status and subsequently regulates up to one-third of the genes in E. coli, either directly or indirectly. Lrp exists predominantly as octamers and hexadecamers (16mers), where leucine is believed to shift the equilibrium toward the octameric state. In this study, we analyzed the effects of three oligomerization state mutants of Lrp in terms of their ability to bind to DNA and regulate gene expression in response to exogenous leucine. We find that oligomerization beyond dimers is required for Lrp’s regulatory activity and that, contrary to previous speculation, exogenous leucine modulates Lrp activity at its target promoters exclusively by inhibiting Lrp binding to DNA. We also show evidence that Lrp binding bridges DNA over length scales of multiple kilobases, revealing a new range of mechanisms for Lrp-mediated transcriptional regulation. IMPORTANCE Leucine-responsive regulatory protein (Lrp) is one of the most impactful regulators in E. coli and other bacteria. Lrp senses nutrient conditions and responds by controlling strategies for virulence, cellular motility, and nutrient acquisition. Despite its importance and being evolutionarily highly conserved across bacteria and archaea, several mysteries remain regarding Lrp, including how it actually responds to leucine to change its regulation of targets. Previous studies have led to the hypothesis that Lrp switches between two states, an octamer (8 Lrp molecules together) and a hexadecamer (16 Lrp molecules together), upon exposure to leucine; these are referred to as different oligomerization states. Here, we show that contrary to previous expectations, it is Lrp’s propensity to bind DNA, rather than its oligomerization state, that is directly affected by leucine in the cell’s environment. Our new understanding of Lrp activity will aid in identifying and disrupting pathways used by bacteria to cause disease.

Two independent experiments were performed with three groups each (sepsis control, sepsis, and sepsis with apoE23 treatment) to investigate the anti-inflammatory effect of apolipoprotein 23 (apoE23) in a mouse model of sepsis induced by S. typhimurium. Survival rates; plasma level variations in tumor necrosis factor (TNF)-α, interleukin (IL)-6, and lipopolysaccharide (LPS); S. typhimurium colony-forming units in the spleen tissue; and mRNA and protein expression levels of low-density lipoprotein receptor (LDLR), LDLR-related protein (LRP), syndecan-1, and scavenger receptor B1 were evaluated in the livers of mice from the three groups. Results found that the survival rate of septic mice treated with apoE23 was 100% within 48 h, while it was only 40% in septic mice without apoE23 treatment (P < 0.001). The plasma LPS, TNF-α, and IL-6 levels and the S. typhimurium load in mice in the apoE23-treated group were significantly lower than those in septic mice (P < 0.05). Moreover, apoE23 restored the downregulated expression of LDLR and LRP in the liver tissue of septic mice. So apoE23 exhibits an anti-inflammatory effect in the mouse model of S. typhimurium-induced sepsis. Further studies are required to understand the mechanisms underlying the anti-inflammatory effects of apoE23. [ABSTRACT FROM AUTHOR]

Contexto: El análisis de la complejidad de los sistemas conlleva la evolución de los modelos de representación de la realidad, la logística ha avanzado de un contexto empresarial a la cadena de suministro, los modelos básicos de logística con parámetros determinísticos requieren representar el comportamiento real estocástico. En este sentido, aparecen la combinación de los modelos de inventario, la localización y el ruteo con enfoque estocástico aplicados a cadenas de suministro. Método: Se desarrolló una revisión sistemática de la literatura en las bases de datos bibliográficas ScienceDirect, ScholarGoogle, SpringerLink, Scopus, SemanticScholar y Scielo, así como en ResearchGate. De los 79 artículos referenciados, el 65 % comprenden entre el 2015 y 2019. Resultados: Se identifican y describen los modelos, a partir de lo cual se propone una taxonomía en cuatro combinaciones, tres de modelos diádicos: LIP, IRP, LRP y un modelo tríadico: LIRP. Se identifican los parámetros estocásticos utilizados en los modelos, los tipos de modelos, los métodos de solución, las funciones objetivo contempladas y el número de eslabones de la cadena contemplados, a partir de los cuales se proponen taxonomías de los diferentes tipos de modelos. Por último, se presentan líneas de trabajo para futuras investigaciones. Conclusiones: La evolución de modelos determinísticos a estocásticos representa un incremento en la complejidad, lo que obliga a desarrollar nuevos métodos de solución con capacidad de encontrar soluciones factibles. Ha sido de reciente interés el desarrollo de modelos y problemas con medidas de desempeño ambiental, social y riesgo humanitario, en el último periodo toman relevancia modelos tríadicos multiproducto y multiperiodo.

Leucine-responsive regulatory protein (Lrp) is an essential transcriptional regulator in prokaryotes. However, the regulatory role of lrp in Vibrio alginolyticus has still not been studied in detail. In this study, an lrp mutant strain was constructed to gain insight into the role of lrp in Vibrio alginolyticus. The absence of lrp significantly enhances swarming motility, biofilm formation, extracellular protease secretion activity, and tolerance to copper ions. The cumulative mortality of zebrafish (Danio rerio) challenged by intraperitoneal injection against the lrp mutant strain reached 68.89%, significantly higher than the 40.00% suffered by fish injected with the wild-type strain. The expression levels of lrp decreased gradually with increasing culture time under the influence of various physicochemical factors. The expression level of lrp was significantly increased after two hours of culture at pH 5, 22°C, 5% NaCl, the presence of 1 mM Cu2+, 1/4/7 mM ferric citrate, 0.1 mg/L NaNO3, and 0.1 mg/L KH2PO4. The mRNA level of lrp decreased significantly after six hours of culture at 37°C, 1% and 5% NaCl, and the presence of 1/7 mM ferric citrate, 0.1/5 mg/L NaNO3, and 0.1/0.5/2.0 mg/L KH2PO4. The expression of lrp increased after ten hours of culture at pH 5/9, 22°C, 1% NaCl, and the presence of 1 mM Cu2+, 7 mM ferric citrate, 5 mg/L NaNO3, and 0.1 mg/L KH2PO4. Overall, this study indicates that lrp negatively controls the virulence of V. alginolyticus, probably by reducing its swarming motility, biofilm formation, extracellular protease secretion activity, and tolerance to copper ions, and that the expression of lrp is affected by numerous physicochemical factors, and is especially up-regulated after 2 hours of culture in bacterial growth.

Wnt morphogens induce signaling via binding their extracellular receptors. Here, we discuss several recent structural studies showing how Wnts engage their receptors frizzled (FZD) and low-density lipoprotein receptor-related protein 5/6 (LRP5/6), how Cachd1 has been shown as an alternative initiator of Wnt signaling, and how lipidated Wnt may be produced and secreted from the cell., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Non-syndromic CMM has a complex phenotype. Abnormal corpus callosum and corticospinal tract processes are suggested mechanisms of the mirror movements. To further explore behavioural and neural phenotype(s) the present study tests the hypothesis that the response readiness network comprising supplementary motor area (SMA) and connections with motor cortex (M1) functions abnormally in CMM., Methods: Twelve participants with (non-syndromic) CMM and a control group (n = 28) were tested on a probabilistic Go-NoGo task while electroencephalography (EEG) was recorded to assess possible group differences in lateralized readiness of voluntary hand movements together with measures of SMA-M1 functional connectivity., Results: The CMM group demonstrated delayed lateralized readiness and stronger functional connectivity between left-brain SMA-M1 regions. Connectivity strength was correlated with measures of behavioural performance but not with extent of mirroring., Conclusions: Abnormalities in brain processes upstream of movement output likely reflect neurocompensation as a result of lifelong experience with mirroring in CMM., Significance: These findings extend the known neural abnormalities in CMM to include brain networks upstream from those involved in motor output and raise the question of whether neurocompensatory plasticity might be involved., (Copyright © 2024. Published by Elsevier B.V.)

Study Objectives: Perimenopausal insomnia (PMI) is associated with observable performance impairments in visual search tasks. This study examines how various cognitive processing stages contribute to search performance delays in PMI compared to healthy controls (HCs)., Methods: We recruited 76 participants diagnosed with PMI and 63 HCs. Event-related potentials (ERPs) were recorded as participants engaged in a visual search task, reporting the orientation of a color popout target within an array of ellipses. We analyzed group differences in behavioral performance and ERP components across cognitive processing stages., Results: Compared to HCs, PMI patients exhibited behavioral response delays, although accuracy was not different between groups. Electrophysiological analyses revealed group differences across several ERP components. Firstly, the N1 component's amplitude increased bilaterally, suggesting enhanced visual sensory processing. Secondly, a slower and smaller N2pc indicated reduced attentional orienting. Thirdly, a decreased SPCN amplitude pointed to deficits in target discrimination. Fourthly, an increased amplitude of the stimulus-locked LRP, with unchanged latency, suggested heightened neural inputs for maintaining motor initiation speed. Fifthly, prolonged response-locked LRP latency indicated slower motor execution. Finally, these changes in ERP components, along with significant correlations between LRP components and insomnia symptoms, suggest potential neural biomarkers for PMI., Conclusions: Our findings provide high-temporal-resolution insights into the neurocognitive disruptions associated with PMI, highlighting how sleep disturbances affect cognitive processing in visual tasks. These insights enhance our understanding of PMI and contribute to discussions on neural mechanisms driving behavioral performance in various conditions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

When neural networks are employed for high-stakes decision-making, it is desirable that they provide explanations for their prediction in order for us to understand the features that have contributed to the decision. At the same time, it is important to flag potential outliers for in-depth verification by domain experts. In this work we propose to unify two differing aspects of explainability with outlier detection. We argue for a broader adoption of prototype-based student networks capable of providing an example-based explanation for their prediction and at the same time identify regions of similarity between the predicted sample and the examples. The examples are real prototypical cases sampled from the training set via a novel iterative prototype replacement algorithm. Furthermore, we propose to use the prototype similarity scores for identifying outliers. We compare performance in terms of the classification, explanation quality and outlier detection of our proposed network with baselines. We show that our prototype-based networks extending beyond similarity kernels deliver meaningful explanations and promising outlier detection results without compromising classification accuracy. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the application value of 3D arterial spin labeling (3D-ASL) for evaluating distal limb ischemic preconditioning to improve acute ischemic stroke (AIS) perfusion. Materials and Methods: A total of 40 patients with AISs treated in our hospital from January 2020 to December 2020 were recruited, and 15 healthy individuals who were examined in our hospital during the same period were included as the control group; all of these participants were scored on the National Institutes of Health Stroke Scale (NIHSS) and examined by MRI. Sequences included conventional sequences, diffusion-weighted imaging (DWI), magnetic resonance angiography (MRA), and 3D-ASL, and cerebral infarct volume and cerebral blood flow (CBF) in the area of the infarct lesion were measured. After 3 months of treatment, patients with AIS were scored on the modified Rankin Scale (mRS) and divided into good prognosis and poor prognosis groups. In total, 55 adult male Sprague--Dawley rats were divided randomly into three groups: 20 in the middle cerebral artery occlusion (MCAO) group, 20 in the MCAO C limb remote ischemic preconditioning (LRP) group, and 15 in the sham group. In total, 48 h after the procedures, conventional MRI, DWI, and 3D-ASL sequence data were collected, and 2,3,5-trphenyltetrazolium chloride monohydrate (TTC) staining and behavioral scoring were performed. CBF was recorded in the infarct lesion area and the corresponding contralateral area, and the affected/contralateral relative values (rCBF) were calculated to compare the differences in rCBF between different groups. The pathological changes in brain tissues were observed by HE staining, and the expression of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in brain tissues was detected by immunofluorescence and real-time quantitative polymerase chain reaction (RT-qPCR). The protein expression of VEGF was detected by western blotting. Results: Hypertension and internal carotid atherosclerosis are high-risk factors for ischemic stroke, and CBF values in the infarct area are significantly lower than those in the corresponding areas on the contralateral side. NIHSS and mRS scores and CBF values have higher specificity and sensitivity for the prognosis of patients with AIS. LRP significantly reduces the infarct area, improves behavioral deficits in rats with cerebral ischemia, reduces neurological injury and histological damage, protects vascular structures, and promotes neovascularization. In addition, 3D-ASL showed a significant increase in brain tissue perfusion in the ischemic area after LRP, and the expression of VEGF and CD31 showed a significant positive correlation with CBF values. Conclusion: Three dimensional (3D) ASL can be used to evaluate LRP to improve stroke perfusion, and its protective effect may be closely related to LRP-induced vascular regeneration. [ABSTRACT FROM AUTHOR]

Over expression of recombinant proteins triggers a cellular stress response (CSR) that down-regulates numerous genes that have a key role in sustaining expression. Instead of trying to individually up-regulate these genes we hypothesized that a superior strategy would be to modulate the expression of global regulators that control the expression of many such downstream genes. Transcriptomic profiling of post induction cultures expressing recombinant asparaginase in Escherichia coli showed the down-regulation of several critical genes many of which were under the control of the global regulator lrp which is known to have a significant impact on both amino acid metabolism and protein translation. Therefore, to ameliorate the deleterious effects of the CSR we decided to supplement the activity of lrp using plasmid-based co-expression. We observed that the test culture containing an additional plasmid expressing lrp under the arabinose promoter gave a 50% higher yield of recombinant L -Asparaginase after 32 h in batch culture compared to the control, which had only one plasmid expressing the recombinant protein. This approach helped us design a better performing strain, which could sustain expression rates for a significantly longer time period. This work illustrates that modifying the expression of regulatory genes could serve as a better strategy to prevent the reprogramming of the cellular machinery which is the hallmark of the CSR and help in the design better hosts for recombinant protein expression. • Global regulatory lrp protein and its 58 directly regulated genes were downregulated post induction of recombinant protein. • Upregulation of lrp expression prevent down-regulation of regulatee genes having synergistic impact on protein expression. • Co-expression of lrp significantly increased recombinant protein yields with sustained expression till stationary phase. • Delayed co-expression of lrp counters the deleterious effects of CSR which is exacerbated in the late log phase. [ABSTRACT FROM AUTHOR]

The spatial-numerical associations of response codes (SNARC) effect reveals that individuals can represent numbers spatially. In this study, event-related potential (ERP) technology was used to probe the effect of verbal-spatial task instructions on spatial-numerical association coding by using digit parity and magnitude judgment tasks, with the numbers 1–9 (except 5) and Chinese word labels ("left" and "right") as experimental materials. The behavioral results of Experiment 1 showed that the SNARC effect was mainly based on verbal-spatial coding and appeared when the stimulus onset asynchrony (SOA) between the presentation of the verbal labels and the target digit was 0 ms. ERP results did not reveal any significant SNARC-related effects in either the N1 or P3 components. The behavioral results of Experiment 2 again showed that the SNARC effect was dominated by verbal-spatial coding. ERP results showed that significant effects related to verbal-spatial coding were found in both the early positive deflection of the stimulus-locked lateralized readiness potential (S-LRP) and the latency of the response-locked LRP (R-LRP). Hence, in this study, the nature of the spatial coding of the digit magnitudes was influenced by the processing of the word labels and affected both the response selection and response preparation stages. [ABSTRACT FROM AUTHOR]

The spatial-numerical associations of response codes (SNARC) effect reveals that individuals can represent numbers spatially. In this study, event-related potential (ERP) technology was used to probe the effect of verbal-spatial task instructions on spatial-numerical association coding by using digit parity and magnitude judgment tasks, with the numbers 1–9 (except 5) and Chinese word labels (“left” and “right”) as experimental materials. The behavioral results of Experiment 1 showed that the SNARC effect was mainly based on verbal-spatial coding and appeared when the stimulus onset asynchrony (SOA) between the presentation of the verbal labels and the target digit was 0 ms. ERP results did not reveal any significant SNARC-related effects in either the N1 or P3 components. The behavioral results of Experiment 2 again showed that the SNARC effect was dominated by verbal-spatial coding. ERP results showed that significant effects related to verbal-spatial coding were found in both the early positive deflection of the stimulus-locked lateralized readiness potential (S-LRP) and the latency of the response-locked LRP (R-LRP). Hence, in this study, the nature of the spatial coding of the digit magnitudes was influenced by the processing of the word labels and affected both the response selection and response preparation stages.

Background: Among prostate cancer (PCa) treatment options, mini-invasive surgical approaches have gained a wide diffusion in the last decades. The aim of this study was to present oncological, functional, and quality of life data after 10 years of follow-up of a prospective randomized controlled trial (RCT) (ISRCTN11552140) comparing robot-assisted radical prostatectomy (RARP) versus laparoscopic radical prostatectomy (LRP) for the treatment of PCa., Methods: Patients with localized PCa were randomized to undergo LRP or RARP between January 2010 and January 2011. Functional (continence and potency) and oncological (prostate-specific antigen, biochemical recurrence [BCR] and BCR-free survival [BCRFS]) variables were evaluated. BCRFS curves were estimated by the Kaplan-Meier method and compared using the log-rank test. Machine learning partial least square-discriminant analysis (PLS-DA) was used to identify the variables characterizing more the patients who underwent RARP or LRP., Results: Seventy-five of the originally enrolled 120 patients remained on follow-up for 10 years; 40 (53%) underwent RARP and 35 (47%) LRP. Continence and potency recovery rates did not show significant differences (p = 0.068 and p = 0.56, respectively), despite a Δ12% for continence and Δ8% for potency in favor of the robotic approach. However, the quality of continence (in terms of International Consultation on Incontinence Questionnaire-Short Form [ICIQ-SF] score) and erection (in terms of International Index of Erectile Function-5 [IIEF-5] score) was significantly better after 10 years in the robotic group (p = 0.02 and p < 0.001). PLS-DA revealed that LRP was characterized by the worst functional-related outcomes analyzing the entire follow-up period. Four (10%) and six (17%) patients experienced BCR in RARP and LRP groups, respectively (p = 0.36), with an overall 10-year BCR-free survival of 88% and 78% (p = 0.16)., Conclusions: Comparable continence and potency rates were observed between RARP and LRP after a 10-year follow-up. However, the RARP group exhibited superior totally dry rate and erection quality. No difference in terms of oncological outcomes was found., (© 2024 The Authors. The Prostate published by Wiley Periodicals LLC.)

Competitor analysis is an essential component of corporate strategy, providing both offensive and defensive strategic contexts to identify opportunities and threats. The rapid development of social media has recently led to several methodologies and frameworks facilitating competitor analysis through online reviews. Existing studies only focused on detecting comparative sentences in reviewcomments or utilized low-performance models. However, this study proposes a novel approach to identifying the competitive factors using a recent explainable artificial intelligence approach at the comprehensive product feature level. We establish a model to classify the review comments for each corresponding product and evaluate the relevance of each keyword in such comments during the classification process. We then extract and prioritize the keywords and determine their competitiveness based on relevance. Our experiment results show that the proposed method can effectively extract the competitive factors both qualitatively and quantitatively. [ABSTRACT FROM AUTHOR]

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Since the discovery of the Escherichia coli leucine-responsive regulatory protein (Lrp) almost 50 years ago, hundreds of Lrp homologs have been discovered, occurring in 45% of sequenced bacteria and almost all sequenced archaea. Lrp-like proteins are often referred to as the feast/famine regulatory proteins (FFRPs), reflecting their common regulatory roles. Acting as either global or local transcriptional regulators, FFRPs detect the environmental nutritional status by sensing small effector molecules (usually amino acids) and regulate the expression of genes involved in metabolism, virulence, motility, nutrient transport, stress tolerance, and antibiotic resistance to implement appropriate behaviors for the specific ecological niche of each organism. Despite FFRPs' complexity, a significant role in gene regulation, and prevalence throughout prokaryotes, the last comprehensive review on this family of proteins was published about a decade ago. In this review, we integrate recent notable findings regarding E. coli Lrp and other FFRPs across bacteria and archaea with previous observations to synthesize a more complete view on the mechanistic details and biological roles of this ancient class of transcription factors. [ABSTRACT FROM AUTHOR]