Search results for: long short-term memory cell

Authors: Abdul Basit, Gildas Lhostis, Bernard Durand

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Shape memory polymers (SMPs) are replacing shape memory alloys (SMAs) in many applications as SMPs have certain superior properties than SMAs. However, SMAs possess some properties like recovery under stress that SMPs lack. SMPs cannot give complete recovery even under a small load. SMPs are initially heated close to their transition temperature (glass transition temperature or the melting temperature). Then force is applied to deform the heated SMP to a specific position. Subsequently, SMP is allowed to cool keeping it deformed. After cooling, SMP gets the temporary shape. This temporary shape can be recovered by heating it again at the same temperature that was given it while heating it initially. As a result, it will recover its original position. SMP can perform unconstrained recovery and constrained recovery, however; under the load, it only recovers partially. In this work, the recovery under the load of an asymmetrical shape memory composite called as CBCM-SMPC has been investigated. It is found that it has the ability to recover under different loads. Under different loads, it shows powerful complete recovery in reference to initial position. This property can be utilized in many applications.

Keywords: shape memory, polymer composite, thermo-mechanical testing, recovery under load

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Authors: Yan Jia China

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The ruins is a kind of historical intention, which is also the current real existence of developing city. Zen culture of ancient China has a profound esthetic emotion, similarly, the west establish the concept of aesthetics of relic along with the Romanism’s (such as Rousseau etc.) sentiment to historical ruins at the end of 18th century. Nowadays, with the decline of traditional industrial society as well as the rise of post-industrial age, contemporary society must face the ruins and garbage problem which is left by industrial society. Commencing from the perspective of emotion and memory, this paper analyzes the importance for emotional needs as well as their existing status of several projects, such as the Capital Steelworks in Beijing (industrial devastation), the Shibati old section in Chongqing (urban slums) and the Old Hurva Synagogue in Jerusalem (ruins of war). It emphasizes urban design which is started from emotion and the sustainable development of city memory through managing the urban ruins which is criticized by people with the perspective of ecology and art.

Keywords: cultural heritage, urban ruins, ecology, emotion, sustainable urban memory

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Authors: Nadia Chagtmi, Nejla Rejab, Noureddine Boulejfen

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This paper presents a calibration approach based on artificial neural networks (ANN) to determine the envelop signal (I+jQ) of a six-port based receiver (SPR). The memory effects called also dynamic behavior and the nonlinearity brought by diode based power detector have been taken into consideration by the ANN. Experimental set-up has been performed to validate the efficiency of this method. The efficiency of this approach has been confirmed by the obtained results in terms of waveforms. Moreover, the obtained error vector magnitude (EVM) and the mean absolute error (MAE) have been calculated in order to confirm and to test the ANN’s performance to achieve I/Q recovery using the output voltage detected by the power based detector. The baseband signal has been recovered using ANN with EVMs no higher than 1 % and an MAE no higher than 17, 26 for the SPR excited different type of signals such QAM (quadrature amplitude modulation) and LTE (Long Term Evolution).

Keywords: six-port based receiver; calibration, nonlinearity, memory effect, artificial neural network

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Authors: Vijaya Madhuri Devraj, Swarnalatha Guditi, Kiran Kumar Bokara, Gangadhar Taduri

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Cell-based strategies may open therapeutic approaches that promote tolerance through manipulation of macrophages to increase long-term transplant survival rates and minimize side effects of the current immune suppressive regimens. The aim of the present study was, therefore, to test and compare the therapeutic potential of MSC and Tregs on macrophage polarization to develop an alternate cell-based treatment option in kidney transplantation. In the current protocol, macrophages from kidney transplant recipients with graft dysfunction were co-cultured with MSCs and Treg cells with and without cell-cell contact on transwell plates, further to quantitatively assess macrophage polarization in response to MSC and Treg treatment over time, M1 and M2 cell surface markers were used. Additionally, multiple soluble analytes were analyzed in cell supernatant by using bead-based immunoassays. Furthermore, to confirm our findings, gene expression analysis was done. MSCs induced the formation of M2 macrophages more than Tregs when macrophages M0 were cultured in transwell without cell contact. From this, we deduced the mechanism that soluble factors present in the MSCs condition media are involved in skewing of macrophages towards type 2 macrophages; similarly, in co-culture with cell-cell contact, MSCs resulted in more M2 type macrophages than Tregs. And an important finding of this study is the combination of both MSC-Treg showed significantly effective and consistent results in both with and without cell contact setups. Hence, it is suggestive to prefer MSCs over Tregs for secretome-based therapy and a combination of both for either therapy for effective transplantation outcomes. Our findings underline a key role of Tregs and MSCs in promoting macrophage polarization towards anti-inflammatory type. The study has great importance in prolongation of allograft and patient survival without any rejection by cell-based therapy, which induce self-tolerance and controlling infection.

Keywords: graft rejection, graft tolerance, macrophage polarization, mesenchymal stem cells, regulatory T cells, transplant immunology

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Authors: Siamak Shahidi, Nasrin Hashemi-Firouzi, Sara Soleimani-Asl, Alireza Komaki

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Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory and cognitive performance. Recently, an involvement of the serotonergic system and their receptors are suspected in the AD progression. In the present behavioral study, the effects of BIMU (selective 5-HT4 receptor agonist) on cognition and memory in the rat model of AD was investigated. Material and Methods: The animal model of the AD was induced by intracerebroventricular (Icv) injection of amyloid beta (Aβ) in adult male Wistar rats. Animals were divided into experimental groups included control, sham, Aβ, Aβ +BIMU groups. The treatment substances were icv injected (1 μg/μL) for thirty consecutive days. Then, novel object recognition (NOR) and passive avoidance learning (PAL) tests were applied to investigate memory and cognitive performance. Results: Aβ decrease the discrimination index of NOR test. Also, it increases the time spent in the dark compartment during PAL test, as compared with sham and control groups. In addition, compared to Aβ groups, BIMU significantly increased the discrimination index of NOR test and decreased the time spent in the dark compartment of PAL test. Conclusion: These findings suggest that 5-HT4 receptor activation prevents progression of memory and cognitive impairment in a rat model of AD.

Keywords: Alzheimer disease, cognition, memory, serotonin receptors

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Authors: Mythri G., Manjunath ML, Girish Babu M., Shireen Swaliha Quadri

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Background: The increase in diabetes among the elderly is of concern because in addition to the wide range of traditional diabetes complications, evidence has been growing that diabetes is associated with increased risk of cognitive decline. Aims and Objectives: To find out if there is any association between blood sugar levels and short-term and working memory status in patients of type 2 diabetes. Materials and Methods: The study was carried out in 200 individuals aged between 40-65 years consisting of 100 diagnosed cases of Type 2 Diabetes Mellitus and 100 non-diabetics from OPD of Mc Gann Hospital, Shivamogga. Rye’s Auditory Verbal Learning Test, Verbal Fluency Test and Visual Reproduction Test, Working Digit Span Test and Validation Span Test were used to assess short-term and working memory. Fasting and Post Prandial blood sugar levels were estimated. Statistical analysis was done using SPSS 21. Results: Memory test scores of type 2 diabetics were significantly reduced (p < 0.001) when compared to the memory scores of age and gender matched non-diabetics. Fasting blood sugar levels were found to have a negative correlation with memory scores for all 5 tests: AVLT (r=-0.837), VFT (r=-0.888), VRT(r=-0.787), WDST (r=-0.795) and VST (r=-0.943). Post- Prandial blood sugar levels were found to have a negative correlation with memory scores for all 5 tests: AVLT (r=-0.922), VFT (r=-0.848), VRT(r=-0.707),WDST (r=-0.729) and VST (r=-0.880) Memory scores in all 5 tests were found to be negatively correlated with the FBS and PPBS levels in diabetic patients (p < 0.001). Conclusion: The decreased memory status in diabetic patients may be due to many factors like hyperglycemia, vascular disease, insulin resistance, amyloid deposition and also some of the factor combine to produce additive effects like, type of diabetes, co-morbidities, age of onset, duration of the disease and type of therapy. These observed effects of blood sugar levels of diabetics on memory status are of potential clinical importance because even mild cognitive impairment could interfere with todays’ activities.

Keywords: diabetes, cognition, diabetes, HRV, respiratory medicine

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Authors: Evgeniya Y. Yuzbasheva, Tigran V. Yuzbashev, Natalia I. Perkovskaya, Elizaveta B. Mostova

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Cell-surface display of lipase is of great interest as it has many applications in the field of biotechnology owing to its unique advantages: simplified product purification, and cost-effective downstream processing. One promising area of application for whole-cell biocatalysts with surface displayed lipase is biodiesel synthesis. Biodiesel is biodegradable, renewable, and nontoxic alternative fuel for diesel engines. Although the alkaline catalysis method has been widely used for biodiesel production, it has a number of limitations, such as rigorous feedstock specifications, complicated downstream processes, including removal of inorganic salts from the product, recovery of the salt-containing by-product glycerol, and treatment of alkaline wastewater. Enzymatic synthesis of biodiesel can overcome these drawbacks. In this study, Lip2p lipase was displayed on Yarrowia lipolytica cells via C- and N-terminal fusion variant. The active site of lipase is located near the C-terminus, therefore to prevent the activity loosing the insertion of glycine-serine linker between Lip2p and C-domains was performed. The hydrolytic activity of the displayed lipase reached 12,000–18,000 U/g of dry weight. However, leakage of enzyme from the cell wall was observed. In case of C-terminal fusion variant, the leakage was occurred due to the proteolytic cleavage within the linker peptide. In case of N-terminal fusion variant, the leaking enzyme was presented as three proteins, one of which corresponded to the whole hybrid protein. The calculated number of recombinant enzyme displayed on the cell surface is approximately 6–9 × 105 molecules per cell, which is close to the theoretical maximum (2 × 106 molecules/cell). Thus, we attribute the enzyme leakage to the limited space available on the cell surface. Nevertheless, cell-bound lipase exhibited greater stability to short-term and long-term temperature treatment than the native enzyme. It retained 74% of original activity at 60°C for 5 min of incubation, and 83% of original activity after incubation at 50°C during 5 h. Cell-bound lipase had also higher stability in organic solvents and detergents. The developed whole-cell biocatalyst was used for recycling biodiesel synthesis. Two repeated cycles of methanolysis yielded 84.1–% and 71.0–% methyl esters after 33–h and 45–h reactions, respectively.

Keywords: biodiesel, cell-surface display, lipase, whole-cell biocatalyst

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Authors: Kalai Lamia, Jilani Faouzi

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Measuring and controlling risk is one of the most attractive issues in finance. With the persistence of uncontrolled and erratic stocks movements, volatility is perceived as a barometer of daily fluctuations. An objective measure of this variable seems then needed to control risks and cover those that are considered the most important. Non-linear autoregressive modeling is our first evaluation approach. In particular, we test the presence of “persistence” of conditional variance and the presence of a degree of a leverage effect. In order to resolve for the problem of “asymmetry” in volatility, the retained specifications point to the importance of stocks reactions in response to news. Effects of shocks on volatility highlight also the need to study the “long term” behaviour of conditional variance of stocks returns and articulate the presence of long memory and dependence of time series in the long run. We note that the integrated fractional autoregressive model allows for representing time series that show long-term conditional variance thanks to fractional integration parameters. In order to stop at the dynamics that manage time series, a comparative study of the results of the different models will allow for better understanding volatility structure over the Tunisia stock market, with the aim of accurately predicting fluctuation risks.

Keywords: asymmetry volatility, clustering, stylised facts, leverage effect

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Authors: Pakakrong Thongdeeying, Srisopa Ruangnoo, Arunporn Itharat

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The rhizomes of Smilax corbularia Kunth have long been used as common ingredients in anticancer preparations. Thus, the objective of this study is to investigate cytotoxicity of S. corbularia and its ingredients against cholangiocarcinoma cell line (KKU-M156) by SRB assay. Ethanolic and water extracts of S. corbularia rhizomes were obtained using the procedures followed by Thai traditional doctors. Bioassay guided isolation was used to isolate cytotoxic compounds. The results revealed that the ethanolic extract of S. corbularia exhibited activity against KKU-M156 cell line with an IC50 value of 84.53±1.62 µg/ml, but the water extract showed no cytotoxic activity. Three flavonoid compounds [astilbin (1), engeletin (2), and quercetin (3)] were isolated from the ethanolic extract. Compound 3 exhibited the strongest activity against KKU-M156 cell line (IC50 = 8.14 ± 1.15 µg/ml), but 1 and 2 showed no cytotoxic activity (IC50 > 100 µg/ml). In conclusion, quercetin showed the highest efficacy against cholangiocarcinoma. These results support the traditional use of this plant by Thai traditional doctors for cancer treatment.

Keywords: cholangiocarcinoma, cytotoxicity, flavonoid, Smilax corbularia

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Authors: Israel B. Bitton

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“Memory” is associated with various phenomena, from physical to mental, personal to collective and historical to cultural. As part of a broader exploration of memory studies in philosophy and science (slated for academic publication October 2021), this specific study employs analytical methods of cognitive psychology and philosophy of memory to theorize that A) the primary human will (drive) is to significance, in that every human action and expression can be rooted in a most primal desire to be cosmically significant (however that is individually perceived); and B) that the will to significance manifests as the will to memorability, an innate desire to be remembered by others after death. In support of these broad claims, a review of various popular culture “touchpoints”—historic and contemporary records spanning literature, film and television, traditional news media, and social media—is presented to demonstrate how this very theory is repeatedly and commonly expressed (and has been for a long time) by many popular public figures as well as “everyday people.” Though developed before COVID, the crisis only increased the theory’s relevance: so many people were forced to die alone, leaving them and their loved ones to face even greater existential angst than what ordinarily accompanies death since the usual expectations for one’s “final moments” were shattered. To underscore this issue of, and response to, what can be considered a sociocultural “memory gap,” this study concludes with a summary of several projects launched by journalists at the height of the pandemic to document the memorable human stories behind COVID’s tragic warped speed death toll that, when analyzed through the lens of Viktor E. Frankl’s psychoanalytical perspective on “existential meaning,” shows how countless individuals were robbed of the last wills and testaments to their self-significance and memorability typically afforded to the dying and the aggrieved. The resulting insight ought to inform how government and public health officials determine what is truly “non-essential” to human health, physical and mental, at times of crisis.

Keywords: cognitive psychology, covid, neuroscience, philosophy of memory

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Authors: Gholizadeh F. F., Goldansaz S. H., Bandani A. R., A. Ashouri

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This study aimed to investigate the direct effects of increasing carbon dioxide (CO₂) concentration on the behavior of Bombus terrestris bumblebees in laboratory conditions to understand the outcomes of the augmentation of this gas in the Earth's atmosphere on the decline of populations of these pollinators. Learning and memory duration of bumblebees were evaluated as two main behavioral factors in social insects at different concentrations of CO₂. In both series of experiments, the behavior of bees under the influence of CO₂ changes compared to the control. Insects kept at high CO₂ concentrations learn less than control bees and spend more time identifying and navigating to discover their food source and access time (nectar consumption). These results showed that bees maybe lose some of their food resources due to poorer identification and act weaker on searching due to less memory and avoiding the enemy in higher CO₂ concentration. Therefore, CO₂ increasing concentration can be one of the reasons for the decline of these pollinating insects' populations by negatively affecting their fitness.

Keywords: Bombus terrestris, CO₂, learning, memory duration

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Authors: Liangliang Tang, Chang Xu, Xingying Chen

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GaInAsSb cells probably show better performance than GaSb cells in low-temperature thermophotovoltaic systems due to lower bandgap; however, few experiments proved this phenomenon so far. In this paper, numerical simulation is used to evaluate GaInAsSb and GaSb cells with similar structures under different radiation temperatures. We found that GaInAsSb cells with n-type emitters show slightly higher output power densities compared with that of GaSb cells with n-type emitters below 1,550 K-blackbody radiation, and the power density of the later cells will suppress the formers above this temperature point. During the temperature range of 1,000~2,000 K, the efficiencies of GaSb cells are about twice of GaInAsSb cells if perfect filters are used to prevent the emission of the non-absorbed long wavelength photons. Several parameters that affect the GaInAsSb cell were analyzed, such as doping profiles, thicknesses of GaInAsSb epitaxial layer and surface recombination velocity. The non-p junctions, i.e., n-type emitters are better for GaInAsSb cell fabrication, which is similar to that of GaSb cells.

Keywords: thermophotovoltaic cell, GaSb, GaInAsSb, diffused emitters

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Authors: Yemima Dani Riani, Anggraini Barlian

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Green turtle (Chelonia mydas) is one of well known long-lived turtle. Its age can reach 100 years old. Senescence in green turtle is an interesting process to study because until now no clear explanation has been established about senescence at cellular or molecular level in this species. Since 1999, green turtle announced as an endangered species. Hence, establishment of fibroblast skin cell culture of green turtle may be material for future study of senescence. One common marker used for detecting senescence is telomere shortening. Reduced telomerase activity, the reverse transcriptase enzyme which adds TTAGGG DNA sequence to telomere end, may also cause senescence. The purpose of this research are establish and identify green turtle fibroblast skin cell culture and also compare telomere length and telomerase activity from passage 5 and 14. Primary cell culture made with primary explant method then cultured in Leibovitz-15 (Sigma) supplemented by 10% Fetal Bovine Serum (Sigma) and 100 U/mL Penicillin/Streptomycin (Sigma) at 30 ± 1oC. Cells identified with Rabbit Anti-Vimentin Polyclonal Antibody (Abcam) and Goat Polyclonal Antibody (Abcam) using confocal microscope (Zeiss LSM 170). Telomere length obtained using TeloTAGGG Telomere Length Assay (Roche) while telomerase activity obtained using TeloTAGGG Telomerase PCR ElisaPlus (Roche). Primary cell culture from green turtle skin had fibroblastic morphology and immunocytochemistry test with vimentin antibody proved the culture was fibroblast cell. Measurement of telomere length and telomerase activity showed that telomere length and telomerase activity of passage 14 was greater than passage 5. However, based on morphology, green turtle fibroblast skin cell culture showed senescent morphology. Based on the analysis of telomere length and telomerase activity, suspected fibroblast skin cell culture of green turtles is not undergo aging through telomere shortening.

Keywords: cell culture, chelonia mydas, telomerase, telomere, senescence

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Authors: Celso Afonso Klein Jr., Henrique Cantarelli, Fernando Portella, Keiichi Hosaka, Eduardo Reston, Fabricio Collares, Roberto Zimmer

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TTo evaluate the influence of preheating self-adhesive cement at 39ºC on cell migration, cytotoxicity and degree of conversion. RelyX U200, Set PP and MaxCem Elite were subjected to a degree of conversion analysis (FTIR-ATR). For the cytotoxicity analysis, extracts (24 h and 7 days) were placed in contact with NIH/3T3 cells. For cell migration, images were captured of each sample until the possible closure of the cleft occurred. In the results of the degree of conversion, preheating did not improve the conversion of cement. For the MTT, preheating did not improve the results within 24 hours. However, it generated positive results within 7 days for the Set PP resin cement. For cell migration, high rates of cell death were found in all groups. It is concluded that preheating at 39ºC caused a positive effect only in increasing the cell viability of the Set PP resin cement and that both materials analyzed are highly cytotoxic.

Keywords: dental cements, resin cements, degree of conversion, cytotoxicity, cell migration assays

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Authors: Reshaa Alruwaili

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This study was inspired by previous studies with young children that found (a) that they need both inhibitory control and working memory when drawing an unfamiliar subject (e.g., animals) by adapting their schema of the human figure and (b) that when drawing something familiar (e.g., a person) they use inhibitory control mediated through fine motor control to execute their drawing. This study, therefore, systematically investigated whether direct effects for both working memory and inhibitory control and/or effects mediated through fine motor control existed when drawing both familiar and unfamiliar subjects. Participants were 95 children (41-66 months old) required to draw both a man and a dog, scored respectively for how representational they were and for differences from a human figure. Regression and mediation analyses showed that inhibitory control alone predicted drawing a recognizable man while working memory alone predicted drawing a dog that was not human-like when fine motor control, age, and gender were controlled. Contrasting with some previous studies, these results suggest that the roles of working memory and inhibitory control are sensitive to the familiarity of the drawing task and are not necessarily mediated through fine motor control. Implications for research on drawing development are discussed.

Keywords: child drawing, inhibitory control, working memory, fine motor control, mediation, familiar and unfamiliar subjects

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Authors: Mehran Fadaeinasab, Hamed Karimian, Najihah Mohd Hashim, Hapipah Mohd Ali

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In this study, three indole alkaloids namely; rauvolfine B, macusine B, and isoreserpiline have been isolated from the dichloromethane crude extract of Rauvolfia reflexa bark (Apocynaceae). The structural elucidation of the isolated compounds has been performed using spectral methods such as UV, IR, MS, 1D, and 2D NMR. Rauvolfine B showed anti proliferation activity on HCT-116 cancer cell line, its cytotoxicity induction was observed using MTT assay in eight different cell lines. Annexin-V is serving as a marker for apoptotic cells and the Annexin-V-FITC assay was carried out to observe the detection of cell-surface Phosphatidylserine (PS). Apoptosis was confirmed by using caspase-8 and -9 assays. Cell cycle arrest was also investigated using flowcytometric analysis. rauvolfine B had exhibited significantly higher cytotoxicity against HCT-116 cell line. The treatment significantly arrested HCT-116 cells in the S phase. Together, the results presented in this study demonstrated that rauvolfine B inhibited the proliferation of HCT-116 cells and programmed cell death followed by cell cycle arrest.

Keywords: apocynacea, indole alkaloid, apoptosis, cell cycle arrest

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Authors: Michael Granado

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The French philosopher Gaston Bachelard’s philosophy of time is articulated in his two works on the subject, the Intuition of the Instant (1932) and his The Dialectic of Duration (1936). Both works present a systematic methodology predicated upon the assumption that our understanding of time has radically changed as a result of Einstein and subsequently needs to be reimagined. Bachelard makes a major distinction in his discussion of time: 1. Time as it is (physical time), 2. Time as we experience it (phenomenological time). This paper will focus on the second distinction, phenomenological time, and explore the connections between Bachelard’s work and contemporary psychology. Several aspects of Bachelard’s philosophy of time nicely complement our current understanding of memory and self and clarify how the self relates to experienced time. Two points, in particular, stand out; the first is the relative nature of subjective time, and the second is the implications of subjective time in the formation of the narrative self. Bachelard introduces two philosophical concepts to explain these points: rhythmanalysis and reverie. By exploring these concepts, it will become apparent that there is an undeniable link between memory, self, and time. Through the use of narrative self, the individual connects and links memories and time together to form a sense of personal identity.

Keywords: Gaston Bachelard, memory, self, time

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Authors: Peien Ma

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Bilingual effect/advantage theorized the positive effect of being bilingual on general cognitive abilities, but it was unknown which factors tend to modulate these bilingualism effects on working memory capacity. This study imposed empirical field research on a group of low-SES emerging bilinguals, Miao people, in the hill tribes of rural China to investigate whether bilingualism affected their verbal working memory performance. 20 Miao-Chinese bilinguals (13 girls and 7 boys with a mean age of 11.45, SD=1.67) and 20 Chinese monolingual peers (13 girls and 7 boys with a mean age of 11.6, SD=0.68) were recruited. These bilingual and monolingual juveniles, matched on age, sex, socioeconomic status, and educational status, completed a language background questionnaire and a standard forward and backward digit span test adapted from Wechsler Adult Intelligence Scale-Revised (WAIS-R). The results showed that bilinguals earned a significantly higher overall mean score of the task, suggesting the superiority of working memory ability over the monolinguals. And bilingual cognitive benefits were independent of proficiency levels in learners’ two languages. The results suggested that bilingualism enhances working memory in sequential bilinguals from low SES backgrounds and shed light on our understanding of the bilingual advantage from a psychological and social perspective.

Keywords: bilingual effects, heritage language, Miao/Hmong language Mandarin, working memory

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Authors: Arash Sepehri Bonab

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Techniques to switch cells between development and differentiation, which tend to be commonly exclusive, are utilized in arrange to supply an expansive cell mass that can perform particular separated capacities required for the tissue to develop. Approaches to tissue engineering center on the have to give signals to cell populaces to advance cell multiplication and separation. Current tissue regenerative procedures depend primarily on tissue repair by transplantation of synthetic/natural inserts. In any case, restrictions on the existing procedures have expanded the request for tissue designing approaches. Tissue engineering innovation and stem cell investigation based on tissue building have made awesome advances in overcoming the issues of tissue and organ damage, useful loss, and surgical complications. Bone tissue has the capability to recover itself; in any case, surrenders of a basic estimate anticipate the bone from recovering and require extra support. The advancement of bone tissue building has been utilized to form useful options to recover the bone. This paper primarily portrays current advances in tissue engineering in different fields of bone and talks about the long-term trend of tissue designing innovation in the treatment of complex diseases.

Keywords: tissue engineering, bone, technologies, treatment

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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Authors: Diwei Lin, Amanda Jh. Tan

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We present a very rare case of de novo large cell neuroendocrine carcinoma of the prostate (LCNEC) in an 84-year-old male on a background of high-grade, muscle-invasive transitional cell carcinoma of the bladder. While NE tumours account for 1% to 5% of all cases of prostate cancer and scattered NE cells can be found in 10% to 100% of prostate adenocarcinomas, pure LCNEC of the prostate is extremely rare. Most LCNEC of the prostate is thought to originate by clonal progression under the selection pressure of therapy and refractory to long-term hormonal treatment for adenocarcinoma of the prostate. De novo LCNEC is only described in case reports and is thought to develop via direct malignant transformation. Limited data in the English literature makes it difficult to accurately predict the prognosis of LCNEC of the prostate. However, current evidence suggesting that increasing NE differentiation in prostate adenocarcinoma is associated with a higher stage, high-grade disease, and a worse prognosis.

Keywords: large cell neuroendocrine cancer, prostate cancer, refractory cancer, medical and health sciences

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Authors: Vladimir Vinnikov

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The paper proposes a model of an inhomogeneous rock mass with initially random distribution of microcracks on mineral grain boundaries. It describes the behavior of cracks in a medium under the effect of thermal field, the medium heated instantaneously to a predetermined temperature. Crack growth occurs according to the concept of fracture mechanics provided that the stress intensity factor K exceeds the critical value of Kc. The modeling of thermally induced acoustic emission memory effects is based on the assumption that every event of crack nucleation or crack growth caused by heating is accompanied with a single acoustic emission event. Parameters of the thermally induced acoustic emission memory effect produced by cyclic heating and cooling (with the temperature amplitude increasing from cycle to cycle) were calculated for several rock texture types (massive, banded, and disseminated). The study substantiates the adaptation of the proposed model to humidity interference with the thermally induced acoustic emission memory effect. The influence of humidity on the thermally induced acoustic emission memory effect in quasi-homogeneous and banded rocks is estimated. It is shown that such modeling allows the structure and texture of rocks to be taken into account and the influence of interference factors on the distinctness of the thermally induced acoustic emission memory effect to be estimated. The numerical modeling can be used to obtain information about the thermal impacts on rocks in the past and determine the degree of rock disturbance by means of non-destructive testing.

Keywords: crack growth, cyclic heating and cooling, rock texture, thermo acoustic emission memory effect

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Authors: Pia Berner Hansson, Robert Murison Anders Lund, Hammar Åsa

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Major Depressive Disorder (MDD) is often associated with high levels of stress and disturbances in the Hypothalamic Pituitary Adrenal (HPA) system, yielding high levels of cortisol, in addition to cognitive dysfunction. Previous studies in this patient group have shown a relationship between cortisol profile and cognitive functioning in the acute phase of MDD and that the patients had significantly less suppression after dexamethasone administration. However, few studies have investigated this relationship over time and in phases of symptom reduction. The aim of the present study was to examine the relationships between cortisol levels after the Dexamethasone Suppression Test (DST) and cognitive function in a long term perspective in MDD patients. Patients meeting the DSM-IV criteria for a MDD were included in the study and tested in symptom reduction. A control group was included. Cortisol was measured in saliva collected with Salivette sampling devices. Saliva samples were collected 4 times during a 24 hours period over two consecutive days: at awakening, after 45 minutes, after 7 hours and at 11 pm. Dexamethasone (1.0 mg) was given on Day 1 at 11 pm. The neuropsychological test battery consisted of standardized tests measuring memory and Executive Functioning (EF). Cortisol levels did not differ significantly between patients and controls on Day 1 or Day 2. Both groups showed significant suppression after Dexamethasone. There were no correlations between cortisol levels or suppression after Dexamethasone and cognitive measures. The results indicate that the HPA-axis functioning normalizes in phases of symptom reduction in MDD patients and that there no relation between cortisol profile and cognitive functioning in memory or EF.

Keywords: depression, MDD, cortisol, suppression, cognitive functioning

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Authors: Marcio Freire Cruz, Naoaki Ono, Shigehiko Kanaya, Carlos Arthur Mattos Teixeira Cavalcante

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The systems that record patient care information, known as Electronic Medical Record (EMR) and those that monitor vital signs of patients, such as heart rate, body temperature, and blood pressure have been extremely valuable for the effectiveness of the patient’s treatment. Several kinds of research have been using data from EMRs and vital signs of patients to predict illnesses. Among them, we highlight those that intend to predict, classify, or, at least identify patterns, of sepsis illness in patients under vital signs monitoring. Sepsis is an organic dysfunction caused by a dysregulated patient's response to an infection that affects millions of people worldwide. Early detection of sepsis is expected to provide a significant improvement in its treatment. Preceding works usually combined medical, statistical, mathematical and computational models to develop detection methods for early prediction, getting higher accuracies, and using the smallest number of variables. Among other techniques, we could find researches using survival analysis, specialist systems, machine learning and deep learning that reached great results. In our research, patients are modeled as points moving each hour in an n-dimensional space where n is the number of vital signs (variables). These points can reach a sepsis target point after some time. For now, the sepsis target point was calculated using the median of all patients’ variables on the sepsis onset. From these points, we calculate for each hour the position vector, the first derivative (velocity vector) and the second derivative (acceleration vector) of the variables to evaluate their behavior. And we construct a prediction model based on a Long Short-Term Memory (LSTM) Network, including these derivatives as explanatory variables. The accuracy of the prediction 6 hours before the time of sepsis, considering only the vital signs reached 83.24% and by including the vectors position, speed, and acceleration, we obtained 94.96%. The data are being collected from Medical Information Mart for Intensive Care (MIMIC) Database, a public database that contains vital signs, laboratory test results, observations, notes, and so on, from more than 60.000 patients.

Keywords: dynamic analysis, long short-term memory, prediction, sepsis

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Authors: Ben Nadler

Abstract:

Cell adhesion plays a vital role in many cell activities. The motivation to model cell adhesion is to study important biological processes, such as cell spreading, cell aggregation, tissue formation, and cell adhesion, which are very challenging to study by experimental methods alone. This study provides important insight into cell adhesion, which can lead to improve regenerative medicine and tissue formation techniques. In this presentation the biological cells adhesion is mediated by receptors–ligands binding and the diffusivity of the receptor on the cell membrane surface. The ability of receptors to diffuse on the cell membrane surface yields a very unique and complicated adhesion mechanism, which is exclusive to cells. The phospholipid bilayer, which is the main component in the cell membrane, shows fluid-like behavior associated with the molecules’ diffusivity. The biological cell is modeled as a fluid-like membrane with negligible bending stiffness enclosing the cytoplasm fluid. The in-plane mechanical behavior of the cell membrane is assumed to depend only on the area change, which is motivated by the fluidity of the phospholipid bilayer. In addition, the presence of receptors influences on the local mechanical properties of the cell membrane is accounted for by including stress-free area change, which depends on the receptor density. Based on the physical properties of the receptors and ligands the attraction between the receptors and ligands is modeled as a charged-nonpolar which is a noncovalent interaction. Such interaction is a short-range type, which decays fast with distance. The mobility of the receptor on the cell membrane is modeled using the diffusion equation and Fick’s law is used to model the receptor–receptor interactions. The resultant interaction force, which includes receptor–ligand and receptor–receptor interaction, is decomposed into tangential part, which governs the receptor diffusion, and normal part, which governs the cell deformation and adhesion. The formulation of the governing equations and numerical simulations will be presented. Analysis of the adhesion characteristic and properties are discussed. The roles of various thermomechanical properties of the cell, receptors and ligands on the cell adhesion are investigated.

Keywords: cell adhesion, cell membrane, receptor-ligand interaction, receptor diffusion

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Authors: Manveen Singh

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Since the very advent of law enforcement, eyewitness testimony has played a pivotal role in identifying, arresting and convicting suspects. Reliant heavily on the accuracy of human memory, nothing seems to carry more weight with the judiciary than the testimony of an actual witness. The acceptance of eyewitness testimony as a substantive piece of evidence lies embedded in the assumption that the human mind is adept at recording and storing events. Research though, has proven otherwise. Having carried out extensive study in the field of eyewitness testimony for the past 40 years, psychologists have concluded that human memory is fragile and needs to be treated carefully. The question that arises then, is how reliable is eyewitness testimony? The credibility of eyewitness testimony, simply put, depends on several factors leaving it reliable at times while not so much at others. This is further substantiated by the fact that as per scientific research, over 75 percent of all eyewitness testimonies may stand in error; quite a few of these cases resulting in life sentences. Although the advancement of scientific techniques, especially DNA testing, helped overturn many of these eyewitness testimony-based convictions, yet eyewitness identifications continue to form the backbone of most police investigations and courtroom decisions till date. What then is the solution to this long standing concern regarding the accuracy of eyewitness accounts? The present paper shall analyze the linkage between human memory and eyewitness identification as well as look at the various factors governing the credibility of eyewitness testimonies. Furthermore, it shall elaborate upon some best practices developed over the years to help reduce mistaken identifications. Thus, in the process, trace out the changing landscape of eyewitness testimony amidst the evolution of DNA and trace evidence.

Keywords: DNA, eyewitness, identification, testimony, evidence

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Authors: Anchana Julsiri, Seree Chadcham

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The present study determined the effects of listening to pleasant Thai classical music on increasing working memory in elderly. Thai classical music without lyrics that made participants feel fun and aroused was used in the experiment for 3.19-5.40 minutes. The accuracy scores of Counting Span Task (CST), upper alpha ERD%, and theta ERS% were used to assess working memory of participants both before and after listening to pleasant Thai classical music. The results showed that the accuracy scores of CST and upper alpha ERD% in the frontal area of participants after listening to Thai classical music were significantly higher than before listening to Thai classical music (p < .05). Theta ERS% in the fronto-parietal network of participants after listening to Thai classical music was significantly lower than before listening to Thai classical music (p < .05).

Keywords: brain wave, elderly, pleasant Thai classical music, working memory

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Authors: Lanlan Xiao, Yang Liu, Shuo Chen, Bingmei Fu

Abstract:

Most cancer-related deaths are due to metastasis. Metastasis is a complex, multistep processes including the detachment of cancer cells from the primary tumor and the migration to distant targeted organs through blood and/or lymphatic circulations. During hematogenous metastasis, the emigration of tumor cells from the blood stream through the vascular wall into the tissue involves arrest in the microvasculature, adhesion to the endothelial cells forming the microvessel wall and transmigration to the tissue through the endothelial barrier termed as extravasation. The narrow slit between endothelial cells that line the microvessel wall is the principal pathway for tumor cell extravasation to the surrounding tissue. To understand this crucial step for tumor hematogenous metastasis, we used Dissipative Particle Dynamics method to investigate an individual cell passing through a narrow slit numerically. The cell membrane was simulated by a spring-based network model which can separate the internal cytoplasm and surrounding fluid. The effects of the cell elasticity, cell shape and cell surface area increase, and slit size on the cell transmigration through the slit were investigated. Under a fixed driven force, the cell with higher elasticity can be elongated more and pass faster through the slit. When the slit width decreases to 2/3 of the cell diameter, the spherical cell becomes jammed despite reducing its elasticity modulus by 10 times. However, transforming the cell from a spherical to ellipsoidal shape and increasing the cell surface area only by 3% can enable the cell to pass the narrow slit. Therefore the cell shape and surface area increase play a more important role than the cell elasticity in cell passing through the narrow slit. In addition, the simulation results indicate that the cell migration velocity decreases during entry but increases during exit of the slit, which is qualitatively in agreement with the experimental observation.

Keywords: dissipative particle dynamics, deformability, surface area increase, cell migration

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Authors: David Pettitt, Benjamin Davies, Georg Holländer, David Brindley

Abstract:

Cellular based therapies, whose origins can be traced from the intertwined concepts of tissue engineering and regenerative medicine, have the potential to transform the current medical landscape and offer an approach to managing what were once considered untreatable diseases. However, despite a large increase in basic science activity in the cell therapy arena alongside a growing portfolio of cell therapy trials, the number of industry products available for widespread clinical use correlates poorly with such a magnitude of activity, with the number of cell-based therapeutics in mainstream use remaining comparatively low. This research serves to quantitatively assess the barriers to the clinical adoption of cell-based therapeutics through identification of unique barriers, specific challenges and opportunities facing the development and adoption of such therapies.

Keywords: cell therapy, clinical adoption, commercialization, translation

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Authors: Radia Chemlal, Salim Mehenni, Dahbia Leila Anes-boulahbal, Mohamed Kherat, Nabil Mameri

Abstract:

The application of the electric field is considered to be a very promising method in cancer therapy. Indeed, cancer cells are very sensitive to the electric field, although the cellular response is not entirely clear. The tests carried out consisted in subjecting the RD cell line under the effect of the continuous electric field while varying certain parameters (voltage, exposure time, and cell concentration). The response surface methodology (RSM) was used to assess the effect of the chosen parameters, as well as the existence of interactions between them. The results obtained showed that the voltage, the cell concentration as well as the interaction between voltage and exposure time have an influence on the mortality rate of the RD cell line.

Keywords: continuous electric field, RD cancer cell line, RSM, voltage

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