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In the conventional setup planning methods, the required fixtures are planned in a sequential order relative to other activities of the setup planning. In the present study, a new approach has been developed and a concurrent method has been proposed for integrating the setup planning and fixture design practice, which paves the way for considering the fixture design principles in parallel to setup planning activities. This eliminates the need to revise the setup plans to remedy the possible conflicts which are common to conventional procedures. The fixture principles have been cast into mathematical relations as a means to developing the proposed method. In the present study, the locating surfaces are determined as the most important step of the fixture system design. The reference faces which cannot be used as locating surfaces are also distinguished, in order for the designer to revise the design of the workpiece. [ABSTRACT FROM AUTHOR]

In cardiovascular disease, a patient's anxiety and depression can increase cardiac rehabilitation duration and recovery. Lavender aromatherapy as a non-pharmacological intervention effective in other contexts may be an efficient intervention to alleviating anxiety and depression in patients with Acute Coronary Syndrome (ACS).

There are various environmental risks in both the construction and operation phases of huge civil projects such as dam construction. As a result, it is critical to implement appropriate risk control and risk mitigation measures before the initiation of the activities posed by these schemes. The goal of this research is to identify and categorize the environmental risks posed by the Amirkabir Dam during its construction and operation phases. After identifying the risks, the risk factors were prioritized using the FMEA method, with the risks being ranked according to their severity, probability of occurrence, and ability to detect. The study’s findings revealed that the highest risk in the dam construction stage is associated with road construction and vehicle exhaust gases (RPNs of 280 and 252, respectively), and the highest risk in the operation phase is associated with borrow area overuse (erosion and sediment downstream of the dam) (RPN of 280).

An integrated manufacturing system needs automated conversion of design information into its manufacturing counterpart. This is partly dealt with in the present study for extracting the manufacturing information for computer-aided process planning systems, including the identification of tool approach direction, attributing the dimensional and geometric tolerances to the machining features, and identification of the reference faces. In spite of extensive study conducted on computer-aided process planning systems, further investigation is still needed to develop automation in attributing tolerances to machining features and identifying the reference faces. The authors have proposed new methods to implement these tasks. A detailed case study has been used to illustrate the application of the developed algorithms. [ABSTRACT FROM AUTHOR]

In this study, the elastic bending of long and rectangular plate resting on unilateral rubber foundation under a concentrated load has been investigated. A new continuum model has been developed to study the rubber foundation reaction. A simplified one-parameter model could thus be obtained for the foundation reaction permitting the parameter to be directly determined without resorting to trial estimation. The governing differential equations have been derived for the plate–foundation system. A numerical–analytical method has been proposed for the exact and closed-form solution of the equations. Several examples have been presented in order to draw a comparison between the results of the proposed solution and the conventional numerical solution. The results have also been compared with the Winkler's mechanical model. Finally, the effect of various parameters on the behaviour of the plate–foundation system has been studied. The results indicate that the length of contact region between the plate and the foundation is influenced by the mechanical and geometrical parameters of the plate and also on the foundation modulus but does not depend on the loading. [ABSTRACT FROM AUTHOR]

The roll bending of sheet metals which rest on a rubber pad has only recently been studied scientifically and is dealt with in the present work. In this process, three different zones can be distinguished along the sheet metal profile, including the undeformed zone, the elastic zone, and the plastic zone. The governing differential equations of the deformation zones were investigated for the elastic and plastic bending of the sheet. The equations were solved analytically for elastic bending and analytically–numerically for plastic bending. The effects of the process parameters were then investigated. The elastic–plastic bending solution was verified by experiments. [ABSTRACT FROM AUTHOR]

Hot isothermal/isostatic pressing machines are technically good candidates for superplastic forming (SPF) of otherwise hard-to-shape materials such as superalloys. These machines are, however, very expensive so that small or medium-size enterprises can not afford them. This has impeded widespread use of SPF processing. In an attempt to alleviate the problem, the authors have developed a laboratory model of an affordable hot isothermal pressing machine with differential gas pressure as the forming medium. Careful selection of process parameters such as temperature, gas pressure, strain rate, and process time as well as monitoring of thickness changes in a workpiece has a pivotal role in successful operation of such machine. It has been illustrated in this article that SPF can be successfully performed with this machine on the basis of process parameters estimated with existing analytical relations. The performance of this machine has been verified by several experiments on SPF of titanium-based sheets, as reported in this article. [ABSTRACT FROM AUTHOR]

The neuropeptide relaxin-3 and its cognate receptor, relaxin family peptide-3 receptors (RXFP3), have been implicated in modulating learning and memory processes, but their specific roles remain unclear. This study utilized behavioral and molecular approaches to investigate the effects of putatively reversible blockade of RXFP3 in the ventral dentate gyrus (vDG) of the hippocampus on spatial and fear memory formation in rats. Male Wistar rats received bilateral vDG cannula implantation and injections of the RXFP3 antagonist, R3(BΔ23-27)R/I5 (400 ng/0.5 μL per side), or vehicle at specific time points before acquisition, consolidation, or retrieval phases of the Morris water maze and passive avoidance learning tasks. RXFP3 inhibition impaired acquisition in the passive avoidance task but not the spatial learning task. However, both memory consolidation and retrieval were disrupted in both tasks following RXFP3 antagonism. Ventral hippocampal levels of the consolidation-related kinase p70-S6 kinase (p70S6K) were reduced RXFP3 blockade. These findings highlight a key role for ventral hippocampal RXFP3 signaling in the acquisition, consolidation, and retrieval of spatial and emotional memories, extending previous work implicating this neuropeptide system in hippocampal memory processing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hippocampal atrophy is increasingly described in many neurodegenerative syndromes in humans, including stroke and vascular cognitive impairment. However, the progression of brain volume changes after stroke in rodent models is poorly characterized. We aimed to monitor hippocampal atrophy occurring in mice up to 48-weeks post-stroke. Male C57BL/6J mice were subjected to an intraluminal filament-induced middle cerebral artery occlusion (MCAO). At baseline, 3-days, and 1-, 4-, 12-, 24-, 36- and 48-weeks post-surgery, we measured sensorimotor behavior and hippocampal volumes from T 2 -weighted MRI scans. Hippocampal volume-both ipsilateral and contralateral-increased over the life-span of sham-operated mice. In MCAO-subjected mice, different trajectories of ipsilateral hippocampal volume change were observed dependent on whether the hippocampus contained direct infarction, with a decrease in directly infarcted tissue and an increase in non-infarcted tissue. To further investigate these volume changes, neuronal and glial cell densities were assessed in histological brain sections from the subset of MCAO mice lacking hippocampal infarction. Our findings demonstrate previously uncharacterized changes in hippocampal volume and potentially brain parenchymal cell density up to 48-weeks in both sham- and MCAO-operated mice.

The role of the anterior thalamic nuclei (ATN) has been proven in different learning and memory tasks. The ATN consist of three main subnuclei, the anterodorsal (AD), anteroventral (AV) and anteromedial (AM), which have different biological characteristics such as distinct circuitry, cell population and neurotransmitter content. The role of ATN subnuclei in learning and memory has been shown in several studies. However, their probable role in different phases of memory including acquisition, consolidation and retrieval are not still well-known. For this purpose, the effect of reversible inactivation of each ATN subnucleus on different memory phases in two behavioral tasks including passive avoidance (PA) and Morris water maze (MWM) was studied. Wister male rats were bilaterally implanted with cannulas above the AD, AV or AM subnucleus in separate experimental groups in order to inject lidocaine (4%) for their temporal inactivation or, equal volume of saline. Animals were trained in the behavioral tasks and different phases of memory were investigated. Our findings indicated that the AV inactivation strongly disrupts all memory phases in the MWM, and consolidation and retrieval phases in the PA tasks. The AM inactivation had no effect on acquisition of both tasks while it impaired the PA consolidation and MWM retrieval. However, the AD inactivation could not disrupt memory phases in the PA task but impaired the MWM retrieval. In conclusion, it seems that the ATN distinct subnuclei differently affect different phases of memory in these two tasks., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Relaxin-3 is a highly conserved neuropeptide abundantly expressed in neurons of the nucleus incertus (NI) , which project to nodes of the septohippocampal system (SHS) including the medial septum/diagonal band of Broca (MS/DB) and dorsal hippocampus, as well as to limbic circuits. High densities of the G i/o -protein-coupled receptor for relaxin-3, known as relaxin-family peptide-3 receptor (RXFP3) are expressed throughout the SHS, further suggesting a role for relaxin-3/RXFP3 signaling in modulating learning and memory processes that occur within these networks. Therefore, this study sought to gain further anatomical and functional insights into relaxin-3/RXFP3 signaling in the mouse MS/DB. Using Cre / LoxP recombination methods, we assessed locomotion, exploratory behavior, and spatial learning and long-term reference memory in adult C57BL/6J Rxfp3 loxP/loxP mice with targeted depletion of Rxfp3 in the MS/DB. Following prior injection of an AAV (1/2) -Cre-IRES-eGFP vector into the MS/DB to delete/deplete Rxfp3 mRNA/RXFP3 protein, mice tested in a Morris water maze (MWM) displayed an impairment in allocentric spatial learning during acquisition, as well as an impairment in long-term reference memory on probe day. However, RXFP3-depleted and control mice displayed similar motor activity in a locomotor cell and exploratory behavior in a large open-field (LOF) test. A quantitative characterization using multiplex, fluorescent in situ hybridization (ISH) identified a high level of co-localization of Rxfp3 mRNA and vesicular GABA transporter (vGAT) mRNA in MS and DB neurons (~87% and ~95% co-expression, respectively). Rxfp3 mRNA was also detected, to a correspondingly lesser extent, in vesicular glutamate transporter 2 (vGlut2) mRNA-containing neurons in MS and DB (~13% and ~5% co-expression, respectively). Similarly, a qualitative assessment of the MS/DB region, identified Rxfp3 mRNA in neurons that expressed parvalbumin (PV) mRNA (reflecting hippocampally-projecting GABA neurons), whereas choline acetyltransferase mRNA-positive (acetylcholine) neurons lacked Rxfp3 mRNA. These data are consistent with a qualitative immunohistochemical analysis that revealed relaxin-3-immunoreactive nerve fibers in close apposition with PV-immunoreactive neurons in the MS/DB. Together these studies suggest relaxin-3/RXFP3 signaling in the MS/DB plays a role in modulating specific learning and long-term memory associated behaviors in adult mice via effects on GABAergic neuron populations known for their involvement in modulating hippocampal theta rhythm and associated cognitive processes.

Asphaltene is a complex macromolecule whose abundance strongly affects the physical and interfacial properties of crude oil. Asphaltene molecules may precipitate during crude oil production/transportation, which may lead to plugging/clogging of wellbores, pipelines, and equipment. In this study, the solubility of asphaltene in toluene has been investigated by calculation of noncovalent interaction energies between asphaltenes in toluene medium. The results of this study revealed that the main interactions in the asphaltene-toluene system are Lifshitz-van der Waals and Lewis acid-base interactions, whereas the electrostatic double layer is of lower comparative order of significance specifically at lower separation distances and lower ζ potentials. However, the repulsive electrostatic double-layer interactions may assist in stabilizing the asphaltene-toluene system based on the comparative values of Lifshitz-van der Waals, Lewis acid-base, and electrostatic double-layer interactions. This is the case especially at higher separation distances and/or higher temperatures where asphaltene particles have greater values of ζ-potential. Furthermore, it is illustrated that when asphaltene has a lower electron-donor parameter, i.e., a lower basicity than toluene, then Lewis acid-base interactions between asphaltenes in toluene are repulsive. This repulsive Lewis acid-base interaction may compensate for the attractive van der Waals interactions between asphaltene particles at low asphaltene basicity. Finally, the electron donor/acceptor component of the surface energy strongly determines the fate of asphaltene in crude oil colloidal system.

At early stages of Alzheimer's disease (AD), soluble amyloid beta (Aβ) accumulates in brain while microglia are in resting state. Microglia can recognize Aβ long after formation of plaques and release neurotoxic mediators. We examined impact of early minor activation of microglia by Toll-like receptors (TLRs) 2 and 4 agonists on Alzheimer's disease-related disturbed synaptic function and spatial memory in rats. Microglial BV-2 cells were treated by 0.1, 1, and 10 μg/mL of the TLRs ligands lipopolysaccharide, monophosphoryl lipid A (MPL), and Pam3Cys for 24 hours. Culture medium was then changed with media containing 1-μM Aβ. Tumour necrosis factor (TNF)-α and CCL3 levels were measured in the supernatant, 24 hours thereafter. One μg of TLRs ligands which was able to release low level of TNF-α and CCL3, was administered intracerebroventricularly (i.c.v) to adult male rats every 3 days for 24 days. At the half of the treatment period, Aβ1-42 was infused i.c.v (0.075 μg/hour) for 2 weeks. Finally, the following factors were measured: memory performance by Morris water maze, postsynaptic potentials of dentate gyrus following perforant pathway stimulation, hippocampal inflammatory cytokines interleukin 1 (IL-1)β and TNF-α, anti-inflammatory cytokines IL-10 and TGF-1β, microglia marker arginase 1, Aβ deposits, and the receptor involved in Aβ clearance, formyl peptide receptor 2 (FPR2). TLRs ligands caused dose-dependent release of TNF-α and CCL3 by BV-2 cells. Aβ-treated cells did not release TNF-α and CCL3, whereas those pretreated with MPL and Pam3Cys significantly released these cytokines in response to Aβ. Low-dose TLRs ligands improved the disturbance in spatial and working memory; restored the impaired long-term potentiation induced by Aβ; decreased TNF-α, and Aβ deposits; enhanced TGF-1β, IL-10, and arginase 1 in the hippocampus of Aβ-treated rats; and increased polarization of hippocampal microglia to the anti-inflammatory phenotype. The ligands increased formyl peptide receptor 2 in both BV-2 cells and hippocampus/cortex of Aβ-treated rats. Microglia can sense/clear soluble Aβ by early low-dose MPL and Pam3Cys and safeguard synaptic function and memory in rats., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Treatment of spinal cord injury by exogenous cells has brought both successful and unsuccessful results. Olfactory ensheathing cells and Schwann cells have been widely used for transplantation purposes. In this study, we investigated the effects of these cells on contused spinal cord by introducing cells into subarachnoid space. Fifty thousand Schwann cells or olfactory ensheathing cells or a mixture of both cell types were transplanted one week after a 3-second clip compression injury at T-9 spinal cord level in rats. Starting from the day one of spinal cord injury, animals were assessed for six months by BBB test and then were sacrificed for immunohistochemistry labeling of the spinal cord injury site. There was no locomotor recovery in any of the treatment groups including controls. Immunohistochemistry assessment indicated positive labeling of P75 and S100 markers in the cell-transplanted groups compared with control. Our data suggest that transplantation of Schwann cells and/or olfactory ensheathing cells into the subarachnoid space does not improve motor recovery in severely injured spinal cord, at least with the number of cells transplanted here. This, however, should not be regarded as an essentially negative outcome, and further studies which consider higher densities of cells are required.

Background Extraneural scar formation is a challenging problem in nerve repair. Rodent models of scar induction, with their high regenerative capacity, suffer from lack of comparable similarities with human cases. In this study, we attempted to find a reliable and reproducible method of extraneural scarring with a significant impact on the peripheral nerve function. Methods A total of 60 rats were divided into three scar induction groups: abrasion (with a small piece of compressed steel wool), mincing (with extracorporeal mincing of adductor muscle and a 5-mm wide strip of the anterior border of the biceps femoris), and electrocoagulation (with a bipolar coagulator). Extraneural scarring was evaluated macroscopically and histologically during 8 weeks. The tibial functional index was used for behavioral analysis. Results Among three different physical methods of scar induction that were applied, electrocoagulation had the most functional impairment (p < 0.001, two-way analysis of variance); whereas mincing produced the most adhesive and intensive scar, morphologically (p < 0.001). Conclusion We conclude that: (1) the impact of the extraneural scar on the nerve is morphologically and functionally different, based on the method of scarring; (2) to achieve a scar model comparable to the human situation, a method in which the involved nerve is functionally impaired, is preferred over the ones that merely produce a bulky scar., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Involvement of brainstem nucleus incertus (NI) in hippocampal theta rhythm suggests that this structure might play a role in hippocampal-dependent learning and memory. In the present study we aimed to address if NI is involved in an avoidance learning task as well as dentate gyrus (DG) short-term and long-term potentiation. Lidocaine was injected into the NI to transiently inactivate the nucleus, and control rats received saline. Role of NI was studied in passive avoidance learning (PAL) in 3 memory phases of acquisition, consolidation and retrieval. Levels of hippocampal phosphorylated p70 were also assessed in rats involved in PAL. Perforant path-DG short-term synaptic plasticity was studied upon NI inactivation before the paired-pulse stimulation, and also before or after tetanic stimulation in freely moving rats. It was found that NI inactivation delayed learning and impaired retention in the PAL task, with decreased levels of phosphorylated p70 in the respective groups. However, short-term plasticity was not affected by NI inactivation. But long term potentiation (LTP) of DG population spike was poorly induced with NI inactivation compared to the saline group, and it had no effect on population excitatory post-synaptic potential. Furthermore, when NI was inactivated after the induction of LTP, there was no difference between the saline and lidocaine groups. These observations suggest that NI has a role in PAL task, and its inactivation does not change the perforant path-DG granule cell synaptic input but decreases the excitability of the DG granule cells. Further studies should elucidate direct and indirect paths through which NI might influence hippocampal activity., (Copyright © 2016. Published by Elsevier Inc.)

Receptor interacting protein 1 (RIP1) has a critical role in initiation of programmed necrosis or necroptosis. RIP1 in a close collaboration with RIP3 not only mediates necroptosis but also is involved in apoptosis and inflammatory signaling. However, the interpretation of the distinct function of RIP1 and RIP3 is complicated. Herein, we demonstrated that RIP1 inhibition in the context of LPS-induced neuroinflammation decreases RIP3 expression. Concomitant administration of Nec-1, specific inhibitor of RIP1, with LPS also attenuated the activating effect of RIP3 on metabolic enzymes, glutamate-ammonia ligase and glutamate dehydrogenase as bioenergetic determinants, in hippocampal and cortical cells. RIP1 inhibition possessed an anti-inflammatory effect and improved the antioxidant capacity against LPS. Interestingly, and opposed to some reports that necroptosis inhibition sensitizes cells to apoptosis, our results showed that RIP1 inhibition attenuates apoptotic cell death in response to LPS. The survival of neuronal function was also confirmed by measuring spontaneous alternations of rats in Y-maze. In conclusion, effects of RIP1 inhibition on RIP3 and cell death provide new approaches to ameliorate neuroinflammation and relative disorders.

Nucleus incertus (NI) is a pontine nucleus which releases mainly GABA and relaxin-3 in rats. Its suggested functions include response to stress, arousal, and modulation of hippocampal theta rhythm. Since the role of NI in learning and memory has not been well characterized, therefore the involvement of this nucleus in spatial learning and memory and the aftermath hippocampal levels of c-fos and pCREB were evaluated. NI was targeted by implanting cannula in male rats. For reference memory, NI was inactivated by lidocaine (0.4 μl, 4%) at three stages of acquisition, consolidation and retrieval in Morris water maze paradigm. For working memory, NI was inactivated in acquisition and retrieval phases. Injection of lidocaine prior to the first training session of reference memory significantly increased the distance moved, suggesting that inactivation of NI delays acquisition in this spatial task. Inactivation also interfered with the retrieval phase of spatial reference memory, as the time in target quadrant for lidocaine group was less, and the escape latency was higher compared to the control group. However, no difference was observed in the consolidation phase. In the working memory task, with inter-trial intervals of 75 min, the escape latency was higher when NI was inactivated in the retrieval phase. In addition, c-fos and pCREB/CREB levels decreased in NI-inhibited rats. This study suggests that nucleus incertus might participate in acquisition of spatial reference, and retrieval of both spatial reference and working memory. Further studies should investigate possible roles of NI in the hippocampal plasticity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Prior animal models have shown that rats sustaining 3-second immediate spinal cord compression had significantly better functional recovery and smaller lesion volumes than rats subjected to compression times of 1 hour, 6 hours, 3 weeks, and 10 weeks after spinal cord injury. We compare locomotor rating scales and spinal cord histopathology after 3 seconds and 10 minute compression times. . Ten rats were assigned into two early (3-second) and late (10-minute) compressive surgery groups. Compressive injury was produced using an aneurysmal clip method. Rats were followed-up for 11 weeks, and behavioral assessment was done by inclined plane test and tail-flick reflex. At the end of the study, the rats were sacrificed, and spinal cord specimens were studied in light and EM. Basso, Beattie and Bresnahan (BBB) locomotor rating scales were significantly better in the early compression group after the 4th week of evaluation (P&lt;0.05) and persisted throughout the remainder of the study. Histopathology demonstrated decreased normal tissue, more severe gliosis and cystic formation in the late group compared to the early group (P&lt;0.05). In EM study, injuries in the late group including injury to the myelin and axon were more severe than the early compression group, and there was more cytoplasmic edema in the late compression group. Spinal cord injury secondary to 3-second compression improves functional motor recovery, spares more functional tissue, and is associated with less intracellular edema, less myelin and axon damage and more myelin regeneration in rats compared to those with 10 minutes of compression. Inclined plane test and tail-flick reflex had no significant difference.

Unlabelled: Objective (s): Scar formation in injured peripheral nerve bed causes several consequences which impede the process of nerve regeneration. Several animal models are used for scar induction in preclinical studies which target prevention and/or suppression of perineural scar. This study evaluates the translational capacity of four of physical injury models to induce scar formation around the sciatic nerve of rat: laceration, crush, mince and burn., Materials and Methods: Functional (Toe out angle), macroscopic, and microscopic evaluations were performed weekly for four weeks and correlation of findings were analyzed., Result: While macroscopic and microscopic findings suggested a well-developed and adhesive fibrosis surrounding the sciatic nerve, functional assessment did not reveal any significant difference between control and experimental groups (P>0.05)., Conclusion: Our study suggests that none of the applied animal models reproduce all essential features of clinical perineural scar formation. Therefore, more studies are needed to develop optimal animal models for translating preclinical investigations.