Whole words. Toggle Sidebar. Zoom Out. More Information Less Information. Enter the password to open this PDF file:. Cancel OK. File name: -. File size: -. By taking a decolonial approach in the main, but not exclusively the authors hope to shift debates in animal studies towards accounting for and delinking from colonial mentalities.
Three poems interweave our selection of chapters, which together forge three lines of inquiry defined by a certain ethos: transhistories of the present, lessons from the bestiary, and animatingephemera. The chapters in this book were originally published as a special issue of Angelaki. Shifting Cultural Frontiers in Late Antiquity explores the transformation of classical culture in late antiquity by studying cultures at the borders - the borders of empires, of social classes, of public and private spaces, of literary genres, of linguistic communities, and of the modern disciplines that study antiquity.
Although such canonical figures of late ancient studies as Augustine and Ammianus Marcellinus appear in its pages, this book shifts our perspective from the center to the side or the margins.
The essays consider, for example, the ordinary Christians whom Augustine addressed, the border regions of Mesopotamia and Vandal Africa, 'popular' or 'legendary' literature, and athletes. Although traditional philology rightly underlies the work that these essays do, the authors, several among the most prominent in the field of late ancient studies, draw from and combine a range of disciplines and perspectives, including art history, religion, and social history.
Despite their various subject matters and scholarly approaches, the essays in Shifting Cultural Frontiers coalesce around a small number of key themes in the study of late antiquity: the ambiguous effects of 'Christianization,' the creation of new literary and visual forms from earlier models, the interaction and spread of ideals between social classes, and the negotiation of ethnic and imperial identities in the contact between 'Romans' and 'barbarians. Hay Edward J. Author : Edward J.
Just-in-time production JIT is receiving widespread recognition among U. With its proven capacity to streamline the manufacturing process, lower inventory, and improve product quality and ROI, JIT may be the basis for a renaissance in American manufacturing. This book details exactly what JIT is, how to implement it, and how to make it work in the context of American business and culture. In clear, practical terms, it discusses how to assess opportunities for change with JIT, how to develop and plan the necessary changes in production and management, and ways of motivating middle management and other employees in a JIT system.
Relying on examples of companies that have implemented JIT--including cutting-edge firms such as Hewlett-Packard--The Just-in-Time Breakthrough clears up several misconceptions about the process while providing managers with models for putting it into action.
The work presented by Metropolitan Mar Severios is a valuable contribution on behalf of churches adhering to miaphysite Christology in the context of ecumenical conversations between church representatives of various christological positions.
The reader will find the arguments of both sides set out with admirable clarity and objectivity, and it is to be greatly hoped that this monograph, with its constructive approach, will contribute towards a better understanding of the two different approaches, miaphysite and dyophysite, to the mystery of the Incarnation.
Finding that the heart of the dialogues is the rivalry between the characters of the Stranger of Elea and Socrates, the author devotes a chapter to each dialogue and explores the Stranger of Elea's criticism that the uncompromising pursuit of knowledge conflicts with the task of weaving together humans into a political community.
The melding of the arguments of Socrates and the Stranger of Elea, the author suggests, is the best path to understanding Plato's political philosophy. Annotation copyrighted by Book News, Inc. And the Word was: 'Hey, you! Everyone has their own opinion, and indeed their own gods, of every shape and size, and all elbowing for space at the top.
In such a competitive environment, shape and size can be pretty crucial to make one's presence felt. So it's certainly not helpful to be reduced to appearing in the form of a tortoise, a manifestation far below god-like status in anyone's book.
In such instances, you need an acolyte, and fast: for the Great God Om, Brutha the novice is the Chosen One — or at least the only One available. He wants peace and justice and brotherly love. He also wants the Inquisition to stop torturing him now, please. Miller Dana R. We also analyzed the transcription profiles of hepatic development-associated genes Fig. The high levels of GSK3 could repress the induction of definitive endoderm [ 36 ].
Epidermal growth factor EGF and dexamethasone Dexa play an important role in hepatic biology and maturation [ 39 ]. Insulin-transferrin-selenite ITS and fasudil also enhance the stability of stem cell cultures and their differentiation [ 40 ].
Therefore, we efficiently and successfully induced definitive endoderm for hepatic differentiation. We also added hHGF and fasudil in step 2 Fig. Finally, we observed cell morphology and stained it for ALB expression.
The oval or polygonal-like structure of the cells was similar, but ALB was more highly expressed on day 14 Fig. We also analyzed the kinetics of gene expressions during HPC differentiation. FBS is still widely used for inducing hepatic differentiation [ 41 ]. However, it causes an acute immune response after transplantation because of xeno-contamination.
Therefore, we substituted 0. First, we analyzed the dynamics of gene expressions associated with hepatocyte-related genes on days 7 and 14 using previous reports [ 42 , 43 ], and compared them with primary human hepatocytes PHH control.
Day 0 were indicated undifferentiated cells, and Day 18 were indicated differentiated HLCs. The efficiency of hepatic differentiation was significantly increased than the conventional one Fig. Finally, because the main functions of hepatocytes are protein synthesis and detoxification, we performed to measure albumin secretion and CYP3A4 activity in media cultured AM-HLCs. The CYP3A4 activity was measured by two independent methods.
Bipotent hepatic progenitor cells provide more efficient rehabilitation than mature hepatocytes after transplantation [ 45 ]. We have reported that day 14 after hepatic differentiation is the best time for transplanting UCM or LD hepatic progenitors [ 9 ]. First, we investigated the highest expression date of CPM and EpCAM , which are critical markers for bi-potential hepatic progenitor cells that can be differentiated into hepatocytes or cholangiocytes [ 43 ].
Second, we observed mitochondrial oxygen consumption rates OCR on days 7, 10, 12, and 14 following differentiation using PVA. Overall OCR levels were highest on day 12 Fig. Spare respiratory capacity is the extra-mitochondrial capacity, which is available under conditions of increased work or stress. Aso, it is considered important for long-term cell survival and function [ 46 ]. In conclusion, when PVA is used in hepatic differentiation for xeno-free conditions, it helped increase AM-MSCs maturation into hepatocytes , and mitochondrial functions to support their transplantation efficiency.
The AM-HPCs were transplanted into the mouse liver failure model to see whether the cells could engraft into functional hepatocytes in vivo. To start with, the protocol to induce liver damage in mice was modified with the inclusion of cyclophosphamide monohydrate CTX along with thioacetamide TAA. TAA is widely used in mice to induce liver failure. However, it requires close monitoring and supportive care of the mice due to lethality before research start [ 47 ].
In our previous work, half the mice that received the highest doses 0. Therefore, we needed a more stable mouse model for transplantation studies. CTX is also toxic to the bone marrow and liver tissue [ 48 ].
Based on our previous work, we devised an improved acute liver failure model using 0. First, we measured the survival rate of the mouse model. A total of 11 mice were inducted into the liver failure model. Two died on day 1, four died on day 2, and five died on day 3 after induction Fig. On day 1 after induction, whole blood was collected from the mouse model and analyzed complete blood counts CBC and blood enzyme analyses.
The modified model had a similar effect on acute liver failure as the TAA model, but the Suzuki score tended to be higher Fig. Nuclei were counterstained with DAPI blue. Left, DNA gel image. PC, human positive control; NC, negative control. One or 3 weeks later, the mice were examined Fig.
Most of the induced model mice were survival before sacrificing and the histological images of the liver were displayed normal morphology, suggesting that both AM-MSCs and AM-HPCs had the therapeutic effect Fig. We could not evaluate the comparison of therapeutic effects among groups in this study.
Three weeks later, human albumin was detected around the hepatic vein of the mouse liver with histological recovery Fig. Additionally, we examined human mtDNA detection in liver tissue.
These results suggest that AM-HPCs can successfully engraft in damaged livers and supported regeneration. The advantage of stem cells for cell therapy would be safety, mass-producibility, and the ability to select the most effective cells.
The ideal stem cells of the future are iPSCs, but there remain issues of safety and insufficient differentiation still exist [ 51 ].
The various stem cells derived from neonatal-related tissues differ in yields and differentiation abilities depending on the origin of the tissue and desired differentiated cell type. AM-MSCs are suitable for mass production because of the large amount of original tissue material. Based on our data, if passage 10 is used for therapy, the AM-MSCs established from a single individual could be transplanted into more than 10, patients without change of characteristics.
Schematic illustration of the overall flow of this study. AM-MSCs were isolated and characterized. Accordingly, the efficiency of hepatic differentiation was low when the conventional protocol was used. To increase efficiency, CHIR and several other factors were added to the definitive and hepatic endoderm induction medium.
Also, FBS was substituted by PVA to provide xeno-free conditions for transplantation and enhance the efficiency of differentiation. The AM-HPCs were successfully transplanted into the liver and spontaneously repopulate in the acute failure liver. We isolated the AM-MSCs from the amniotic membrane, which generally was isolated epithelial cells [ 52 ]. For obtaining amniotic epithelial cells, a collagen-coating plate or EGF supplement was needed. MHC class 1b is known as an expression in amnion derived-epithelial cells [ 29 ].
Also, EpCAM, which is a positive expression in the epithelium derived from the anionic membrane and hepatic progenitor cells [ 53 , 54 ], was rarely expressed in AM-MSCs. AM-MSCs can be isolated non-invasively like neonatal-related tissues, and easily banked depending on their characteristics.
Matching HLA type or inhibiting MHC expression can reduce or eliminate the use of immunosuppressive drugs, which are unpleasant and can cause side effects [ 56 ]. However, additional molecules, such as PD-L1, HLA-E, and CD47, have also been recently identified supporting and describing the lack of immunorecognition upon transplantation in allogenic and xenogenic settings [ 57 ].
Therefore, AM-MSCs can be candidate cells for universal donors that have applied gene-editing technology. Thus, we realized that different differentiation protocols might be necessary depending on the origin of the cells.
Fasudil is a known ROCK inhibitor and only approval for clinical and it is similar to Y for using cell culture and differentiation [ 40 ]. FBS can contaminate cells during cell culture and differentiation, resulting in the presence of xeno-antigens and infectious agents that can provoke graft-versus-host disease [ 64 ].
It can also lead to differences between batches [ 65 ]. Hence, FBS must be replaced with an alternative supplement to achieve therapeutic outcomes in patients, but its use is still popular for hepatic differentiation despite the risks associated with transplantation [ 41 ].
Polyvinyl alcohol PVA is a water-soluble synthetic polymer and has been used as a substitute for bovine serum albumin BSA in culture media for mouse preimplantation embryos [ 66 ]. It is also used in various human cell expansion and differentiation procedures for therapeutic applications, including hepatic differentiation from PSCs [ 67 , 68 , 69 , 70 ]. In previous studies, TAA is widely used in hepatic disease studies in models.
However, TAA-induced models have difficulties controlling because of side effects [ 47 ]. For this reason, mouse models were easily dead when TAA was used. In addition, the model was not well induced in a low dose of TAA. Therefore, we used CTX, which is also known as toxic to the liver, and expected that CTX can be affected by the stability and liver damage of the mouse model.
To identify optimal transplanting cells, we transplanted AM-MSCs, day 11, day 12, and day differentiated cells into the mouse model.
Even though GSK3 inhibitors were used in a pre-clinical and clinical study for treating cancer [ 73 ], it may not be an efficient method to use AM-MSCs along with GSK3 inhibitors for in vivo differentiation due to the side effect or dosage of chemicals [ 74 , 75 ]. On day 12, differentiated cells were the best conditions in terms of the number of human albumin-positive cells in the mouse liver.
This study established a more effective hepatic differentiation protocol for AM-MSCs by analyzing transcriptome profiles. Moreover, our findings suggested that PVA can be a suitable alternative to FBS in the differentiation for clinical trials.
Finally, the results of in vivo experiment-supported AM-HPCs can be repopulated in the acutely injured livers and were spontaneously rescued by liver failure.
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Lee WM. Standardised annual site-level values for each acoustic index were fitted as the response variable, with latitude, longitude and year continuous as fixed effects.
To account for non-independence of soundscapes from the same site, random effects of site and year were included in all models, along with route and state North America models, Eq.
While significant spatial autocorrelation was found, the sizes of the estimates were negligible Supplementary Table 6 and therefore this is subsequently ignored. To visualise the large-scale annual variation in acoustic properties we refitted these models with year included as a categorial rather than a continuous variable, with predictions from these models providing continent-level annual estimates for each acoustic index Fig.
To explore the relationships between site-level trends in each acoustic index, we fitted GLMs with the standardised annual values for each index as the response variable and year continuous as the explanatory variable Eq. This resulted in an independent estimate of the rate of change in each acoustic index at each site. All statistical analyses were carried out in R v3.
Standardised annual site-level values of the total number of a individuals or b species were fitted as response variables, with latitude, longitude and year continuous as fixed effects. To account for non-independence in community structure from the same site, random effects of site and year were included in all models, along with route and state North America models or country Europe models. Model structures were therefore equivalent to those set out in Eqs. We then refitted these models including year as a categorial rather than a continuous variable to visualise the large-scale annual variation, and used predictions from these models to provide continent-level annual estimates for total abundance and species richness Supplementary Fig.
To explore the site-level relationships between trends in total number of individuals, total number of species and acoustic indices, we first fitted GLMs with either the standardised total number of a individuals or b species as response variables and year continuous as the explanatory variable at each site.
These models were therefore equivalent in structure to that described in Eq. We then fitted separate GLMMs for each acoustic index, in each continent, in turn with site-level trend in acoustic index as the response variable and site-level trends in the total number of individuals and the total number of species and their interaction as fixed effects.
State was included as a random effect in the North American models and country as a random effect in the European models. To incorporate the error associated with site-level trend estimates we used a bootstrapping procedure in our assessment of the significance of the modelled effects. We generated new estimates for each variable site-level trend in: acoustic index, total number of individuals and total number of species by randomly sampling from a normal distribution with a mean equal to the site-level trend and standard deviation equal to the standard error of the site-level trend.
The GLMMs were then fitted over each of the datasets separately. Non-significant interaction terms were removed from the models. Further information on research design is available in the Nature Research Reporting Summary linked to this article. The North American bird monitoring data are available directly from U. Bauman, A. Leitzmann, M. Pergams, O. Is love of nature in the US becoming love of electronic media? Article Google Scholar.
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