Un cambio cualitativo en la mercantilizaci

Un cambio cualitativo en la mercantilización de los vínculos sociales está en curso, empujado además por la disolución de anteriores solidaridades: privatización de los servicios de salud, de la educación, de la jubilación, antes instituidos como derechos; imposición de la flexibilidad laboral, precarización de la contratación, alargamiento de la jornada laboral, desmantelamiento de los contratos colectivos y los derechos del trabajo; en otras palabras, la destrucción de un mundo de socialidades humanas antes conquistadas y establecidas no sólo como derechos sino como niveles civilizatorios de las relaciones entre los humanos.
Esta subsunción de la vida humana al mundo y las exigencias de la relación de capital transita hoy también por la subordinación de la naturaleza y de procesos biológicos constitutivos de la reproducción natural de la vida. En la realización del ser de tal relación se despliegan formas antes impensables de colonización de la naturaleza y de la vida humana. La subordinación de los procesos naturales NU7441 los procesos del capital y a su dinámica es uno de los fenómenos que define la actual mutación epocal, impuesta “por la hegemonía de la voluntad puramente cósica del mundo de NU7441 las mercancías habitadas por el valor económico capitalista”.
Una voluntad puramente cósica: una voluntad inhumana encarnada en el mundo en apariencia inmaterial de las finanzas y en las cosas en tanto mercancías y no como objetos de la creación, el intercambio y el disfrute de los seres humanos y sustentada en el poder material de los dueños del dinero, las armas y las tecnologías. Son las máscaras de una nueva barbarie a las puertas de la Ciudad, tal vez aquella que entrevió la mente deslumbrante de Rosa Luxemburg.

10.
El robo, la depredación, el pillaje y la apropiación de bienes comunes atraviesan la historia del capital desde la conquista de América y el cercamiento de las tierras comunales en la Inglaterra de los siglos xvi al xviii hasta el saqueo colonial y los modernos mecanismos tributarios del sistema financiero internacional. En todos los casos, y sostenidos siempre por la violencia estatal, los procesos de acumulación por despojo pasan por la destrucción de otras matrices civilizatorias y por la incorporación de productores antes autónomos en la red salarial del mercado capitalista.
Microelectrónica, informática, ingeniería genética y nanotecnología permiten que la subsunción de naturaleza, conocimientos y trabajo humano en los circuitos de valorización rompa hoy con límites antes insuperables: biodiversidad, creación intelectual, saberes locales, códigos genéticos, espacio radioeléctrico, espacio aéreo, energía eólica, sangre y órganos humanos, la biósfera entera y aún recursos que son condición elemental de la reproducción de la vida como el agua y las semillas.

11.
El trabajador mundial en formación va adquiriendo y refinando así, en dura lucha por su afirmación y su existencia, una nueva sutileza en la creación de renovadas e inéditas formas de costumbres en común, conocimientos compartidos, organización, solidaridad, resistencia y rebelión. La rebelión de las mujeres contra la dominación masculina, con rasgos diferentes según sociedades y culturas pero perfil similar en cuanto estado de protesta y de insumisión contra el estado de cosas dominante, es parte componente de este proceso y en casos o momentos específicos suele ser el rasgo dominante.

Ω
Este proceso humano, nuevo y sin fronteras, de experiencia, cultura y organización lleva y pide sus tiempos. Pero es también necesario, inescapable y recurrente, tanto como la reproducción del trabajo viviente en los innumerables mundos y tiempos de nuestras vidas. Lo describió Miguel Hernández en los años treinta del pasado siglo, lo cantaron Paco Ibáñez y Joan Manuel Serrat:

Introducción

However the decrease in score between chemical

However, the decrease in score between chemical extraction and direct smear from over 2.0 to 1.70–2.00 did not overall change the final correct identifications (202 vs. 194) by Biotyper 3.0 software (0.05<<0.1), (). Furthermore, other reports have previously suggested that a cut off of the score>1.70 was sufficient for accurate identification of spp. and other species. Similarly, Alatoom et al. demonstrated that a cut off of 1.70 was sufficient to identify the genus of Corynebacterium spp. extraction.
Fourteen of unidentified isolates after chemical extraction were subjected to further testing by 16S rDNA sequencing (21, ). Identification using 16S rDNA sequence analysis indicated 5 of 14 unidentified isolates were not in the Bruker Biotyper version 3.0 database. These five isolates are (=1), (=1), (=1), (=2). Hence the both chemical extraction and direct smear could not identify these isolates. Another five isolates which were not identified by either chemical extraction or direct smear were (=1), spp. (=2), (=2), spp. It is noted that these were among the genus that had a relatively decreased score following direct smear (). Surprisingly, direct smear identified four isolates not identified following chemical extraction (), these MK-571 sodium salt hydrate four isolates had no any colony growth which could result in no identification by chemical extraction because there were not enough cell mass for extraction.
Two methods have been described for the preparation of bacteria for identification by MALDI-TOF MS, one is direct colony smear on the target plates (with or without the addition of formic MK-571 sodium salt hydrate for extraction), the other is the standard ethanol/formic acid protein extraction in which 70% formic acid is added to the ethanol-washed cell pellet, mixed, and followed by addition of acetonitrile and then supernatant is spotted to the target plate. The direct smear method is fast and simple, but the results are sometimes inconsistent compared to the stand chemical extraction. This study demonstrated anaerobic bacteria could be identified by direct smear methods. The results indicate not only that direct smear may be non-inferior to chemical extraction, but also that direct smear may allow additional identifications inaccessible to chemical extraction. The results also underline, as describe elsewhere, that the lack of certain anaerobic species such as and in the database of Biotyper 3.0 are the limit of MALDI-TOF MS. For example, the previous studies have already reported that the lack of the species in the Biotyper database led the system to identify as with high confidence score. Although the mass spectrum of is in the database, the system failed to identify this strain accurately (), this may be due to only a unique peak profile of the single strain in the database which might not be enough to represent the diversity of entire species and lead to such problems. Hence, increasing the number of representative spectra for species might lead Biotyper software to more accurately identify this species. Although company has been increasing the representatives of microorganism species of database in the systems, it may still be updated and expanded through addition of in-house spectra from encountered clinical strains. Therefore, the impact of our study was to increment the Biotyper3.0 database with the spectra of all the strains identified through 16S rDNA sequence analysis. In addition to the number of the reference strains in the database, many other factors may affect the identification by Biotyper, such as the cell wall rigidity, culture condition and bacterial culture age. Our experiments indicate that the number of cells spotted on the target plate has also been shown to influence the identification by direct smear methods (data not shown), too many bacteria cells may overwhelm the lysis of formic acid and matrix solution and hence the cells may not be properly disrupted. We found that 1×10–10 bacterial cells resulted in the good spectral resolution. Smearing cells evenly on the target plates is also critical to achieve good results.

Part II of this study addresses the design

Part II of this ldh assay study addresses the design in a supposed operationalization phase that was guided by both data sets of Part I. Furthermore, the data were used to develop a checklist for architects. The design was based on the joint description of a fictional persona by two of the authors (JVH and AE). The persona was operationalized in a design scenario, which is described as a sequence of the rooms and spaces, and the way design features contribute to a sense of home. Moreover, the retrofitting project also incorporated design features that address the independence of residents and human factors of care professionals. The design of the apartment was applied in the actual retrofitting of an apartment inside an existing nursing home in Eindhoven, the Netherlands. The surface area of the apartment was 58m2, which is relatively large for Dutch standards. The apartment would be used as a test and training facility for a nursing home organization and its care professionals and residents.

Results: feeling at home in nursing homes and the role of the built environment
The themes and quotes of both data sets were merged, and five “architectural” themes were identified, which reflect the state of the art of the scientific literature and residents’ perspectives. The built environment includes the layout of a space, its interior design, and the surroundings. Results from the literature and qualitative study from the perspective of residents, their family members, and staff show that the following factors contribute to a sense of home: private and public spaces, personal belongings, technology, look and feel, and the outdoors and location (Rijnaard et al., 2016; van Hoof et al., 2016a). These factors constitute the theme “built environment.” This theoretical section outlines how these factors influence the sense of home.

Results: operationalization and design guidelines in constructing a sense of home

Discussion, conclusions, and implications for design practice
This study found that the built environment—both from theoretical and user-centered perspectives—can contribute to a sense of home in nursing homes. The study introduced a novel and reliable overview that evaluates the impact of architectural programming and design in creating a sense of home in nursing homes. The sense of home is composed of different scale levels, from the connection with outdoors to the quality of furniture and architectural layout of the room. A particular apartment was refurbished to demonstrate how the architectural themes are operationalized and to connect both data sets in architectural practice. The construction of demonstration dwellings stimulates the discussion and education on the role of architectural features in supporting adequate healthcare and improving the quality of living at an old age (van Hoof and Kort, 2009; van Hoof et al., 2013). The retrofitting of the apartment is an example of how scientific research results are translated into an actual architectural design, and is therefore an example of integrated and evidence-based design (van Hoof et al., 2015b). Through the evidence-based design, architects can bridge the gap between the realms of evidence-based healthcare and architecture. The Center for Health Design (2017) defines evidence-based design as “the process of basing decisions about the built environment on credible research to achieve the best possible outcomes.” This design process includes eight steps: defining evidence-based goals and objectives; creating design concepts; collecting baseline performance measures; monitoring of design implementation; and constructing and executing a post-occupancy evaluation. This process is in accordance with the study of Brawley (2005), who stated that the goal of evidence-based design is to improve outcomes and continuously monitor the success of designs for subsequent decision making. The step of conducting a post-occupancy evaluation with tenants is scheduled; centriole evaluation is according to the effects of the built environment on the sense of home. Through the use and occupancy of the apartment, the real-life experiences of residents and professionals are collected, for example, through workshops and qualitative research. For instance, a psychogeriatric training school is offered by a nursing home organization, wherein the participants take care of professionals as a part of their training. The caregivers experimented with features in the apartment and discussed issues, such as privacy and implications for their own practice. Their feedback and that of other visitors are collected in a special “guestbook.” Thus, the apartment service is a platform that can be improved step-by-step in an ongoing design effort. For example, during the renovation projects, good practices are shared and implemented throughout the organization and even with the wider community.

This work was supported by grants from and L

This work was supported by grants from , and . L.S. received fellowship from ANII (Agencia Nacional de Investigación e Innovación, Uruguay); S.G., J.Z. and B.D. from CNPq, P.S., A.C. and M.A.S. from FIOCRUZ.

Introduction
CXCL12–CXCR4 axis plays important roles during CNS development, controlling cerebellar neuronal progenitor cells (NPC) migration (Ma et al., 1998; Zou et al., 1998), and increasing cerebellar and cortical NPC proliferation (Klein et al., 2001; Wu et al., 2009). In the mature brain, CXCL12 regulates neural stem/progenitor cell (NSC) occupancy of the subventricular zone (SVZ) vascular niche, and upregulates EGFR and integrin α6 expression stimulating the exit and migration of NSC-derived neuroblasts from the SVZ to the olfactory bulb (Kokovay et al., 2010). Involvement of CXCL12 and CXCR4 in brain pathologies has also been described. Migration of NSC towards a brain tumor expressing CXCL12 is mediated by the activation of CXCR4 (van der Meulen et al., 2009). Stroke and traumatic injuries to the CNS lead to an inflammatory response that includes local secretion of several chemokines that, among other effects, attract NSC-derived neuroblasts from the SVZ (Robin et al., 2006; Takeuchi et al., 2007; Itoh et al., 2009; Galindo et al., 2011; Jaerve and Müller, 2012).
CXCL12 binds and activates two G-protein coupled receptors, CXCR4 and CXCR7. Migration and proliferation of NSC and NPC are regulated via activation of CXCR4, whereas the activation of CXCR7 leads to cell survival (Bakondi et al., 2011). To activate CXCR4, CXCL12 binding domain formed by the amino buy pilocarpine hydrochloride residues 12–17 (RFFESH) binds to CXCR4 acting as an initial docking site for CXCL12. Following binding, the activation domain composed of amino acid residues 1–8 (KPVSLSYR) binds to the N-terminal end of the receptor, inducing a conformational change that, in turn, allows binding of G-protein to the intracellular domains of the receptor, leading to activation of signaling pathways involved in the control of migration, proliferation and survival (Crump et al., 1997; Huang et al., 2003; Saini et al., 2011).
Due to CXCL12 pleiotropic effects there is increasing interest to investigate this chemokine as a target for therapeutic strategies to treat a number of brain pathologies. CXCL12 pretreatment preserved dendritic spines of hippocampus neurons submitted to neurotoxicity induced by amyloid-β peptide oligomers in vivo (Raman et al., 2011). Increase in CXCL12 expression by astrocytes after brain ischemia attracts transplanted human umbilical cord cells expressing CXCR4 to the injury site. Inhibition of CXCL12 activity by neutralizing antibodies in vivo resulted in significant reduction in cord blood cells at the injured area, reinforcing the view that CXCL12–CXCR4 axis activates pathways that are keys for homing of CXCR4 expressing cells (Rosenkranz et al., 2010).
The use of CXCL12 to increase chemotaxis and improve survival of NSC to spinal cord and traumatic brain injuries (SCI, TBI) is an approach that has been explored by several groups, but there are still many molecular and cellular issues to be addressed. Here, we provide evidence that a synthetic peptide analogous to the N-terminal portion of CXCL12 containing the receptor binding and activating domains enhances chemotaxis of neuroblasts from the SVZ to an injured area in the cortex. Moreover, this effect seems to be mediated by upregulation of CXCL12 locally, possibly by astrocytes, as indicated by our in vitro experiments. The synthetic peptide is also able to promote NSC proliferation in vitro, without affecting differentiation. A modified peptide, in which we substituted cysteines 9 and 11 by alanines, was not chemotactic for CXCR4 expressing cells but reduced GFAP expression, suggesting that it could be useful to reduce astrocyte reaction in vivo. The data we present here suggest that the approach of using synthetic peptides that mimic CXCL12 chemotactic effect is relevant for the development of new therapeutic strategies to treat TBI and add information regarding the role of CXCL12 N-terminal end on its different biological activities.

br Materials and methods br Author

Materials and methods

Author disclosure statement

Acknowledgments
We thank Muscle Tissue Culture Collection (MTCC) for providing the sample. The Muscle Tissue Culture Collection is part of the German network on muscular dystrophies (MD-NET, service structure S1, 01GM0601) and the German network for mitochondrial disorders (mito-NET, project D2, 01GM0862) funded by the German ministry of education and research (BMBF, Bonn, Germany). The Muscle Tissue Culture Collection is a partner of EuroBioBank (www.eurobiobank.org) and TREAT-NMD (www.treat-nmd.eu). This work was supported by grants from the “Centro de Investigación Biomédica en Red en enfermedades raras” (CIBERER) (Grant 13-717/132.05 to RG), the “Instituto de Salud Carlos III” [Fondo de Investigación Sanitaria and Regional development fund (ERDF/FEDER) funds PI10/0703 and PI13/00556 to RG and PI15/00484 to MEG], “Comunidad Autónoma de Madrid” (Grant number S2010/BMD-2402 to RG); TG receives grant support from the Universidad Autónoma de Madrid (FPI-UAM) and FZD from the Ministerio de Educación, Cultura y Deporte (Grant FPU13/00544). MEG is staff scientist at the “Centro de Investigación Biomédica en Red en Enfermedades Raras” (CIBERER).

Resource table:

Resource details
The generation of the human iPSC line, GFM1SV.25, was carried out using non-integrative Sendai viruses containing the reprogramming factors, OCT3/4, SOX2, CMYC, KLF4 (Takahashi et al., 2007). For this purpose, fibroblasts from a described patient with a severe mitochondrial encephalopathy were obtained (Brito et al., 2015). The patient\’s fibroblasts carried two inherited tlr signaling mutations in the GFM1 gene (c.1404delA; p.Gly469Valfs*84 and c.2011C>T; p.Arg671Cys). The presence of these mutations in the iPSC line was evaluated and confirmed by Sanger sequencing (Fig. 1A). GFM1SV.25 iPSC colonies displayed a typical ES-like colony morphology and growth behavior (Fig. 1B) and they stained positive for alkaline phosphatase activity (Fig. 1C). We confirmed the clearance of the vectors and the exogenous reprogramming factor genes by RT-PCR after eight culture passages (Fig 1D). The endogenous expression of the pluripotency associated transcription factors OCT4, SOX2, KLF4, NANOG, CRIPTO and REX1 was also evaluated by RT-PCR (Fig. 1E). Immunofluorescence analysis revealed expression of transcription factors OCT4, NANOG, SOX2 and surface markers SSEA3, SSEA4, TRA1-60 and TRA1-81 characteristics of pluripotent ES cells (Fig. 1F). Promoters of the pluripotency associated genes, OCT4 and NANOG, heavily methylated in the original fibroblasts were almost demethylated in the GFM1SV.25 line suggesting an epigenetic reprogramming to pluripotency (Fig. 1G). The iPSC line has been adapted to feeder-free culture conditions and displays a normal karyotype (46, XX) after more than twenty culture passages (Fig. 1H). We also confirmed by DNA fingerprinting analysis that the line GFM1SV.25 was derived from the patient\’s fibroblasts (Fig. 1I). Finally, the capacity of the generated iPSC line to differentiate into the three germ layers (endoderm, mesoderm and ectoderm) was tested in vitro using an embryoid body based assay (Fig. 1J).

Materials and methods

Author disclosure statement

Acknowledgments
This work was supported by grants from the “Centro de Investigación Biomédica en Red en enfermedades raras” (CIBERER) (Grant 13-717/132.05 to RG), the “Instituto de Salud Carlos III” [Fondo de Investigación Sanitaria and Regional development fund (ERDF/FEDER) funds PI10/0703 and PI13/00556 to RG and PI15/00484 to MEG], “Comunidad Autónoma de Madrid” (Grant number S2010/BMD-2402 to RG); TG receives grant support from the Universidad Autónoma de Madrid (FPI-UAM) and FZD from the Ministerio de Educación, Cultura y Deporte (Grant FPU13/00544). MEG is staff scientist at the “Centro de Investigación Biomédica en Red en Enfermedades Raras” (CIBERER).

br Experimental Procedures br Author Contributions br

Experimental Procedures

Author Contributions

Acknowledgments

Introduction
Intestinal crypts contain stem cells and their transit-amplifying (TA) daughter cells. Cells exiting the proliferative crypts onto the villi terminally differentiate into enterocytes, goblet cells, and enteroendocrine cells. Paneth cells escape the crypt-villus flow by migrating to crypt bottoms, where they live for several weeks (Bjerknes and Cheng, 2006). With the exception of stem cells and Paneth cells, the murine small intestinal epithelium is renewed approximately every 5 days (van der Flier and Clevers, 2009).
About 14 Lgr5+ stem cells reside intermingled with the Paneth cells at the very bottom of the crypts, where they divide and give rise to all the cell types mentioned above (Barker et al., 2007; Snippert et al., 2010). A second pool of long-lived, label-retaining cells has been postulated to exist at a position directly above the Paneth cells (Potten, 1977; Potten et al., 1974). These so-called +4 cells express markers such as Bmi1 (Tian et al., 2011), Lrig1 (Powell et al., 2012), and HopX (Takeda et al., 2011). Paradoxically, Lgr5+ stem cells also express these markers (Muñoz et al., 2012). A recent study reconciled these findings by showing that noncycling Paneth/enteroendocrine cell precursors coexpress Lgr5 and the +4 markers, and can revert to an Lgr5-stem cell phenotype upon damage (Buczacki et al., 2013; Muñoz et al., 2012; reviewed in Clevers, 2013).
Intestinal stem cells were identified and initially characterized with the use of an Lgr5-eGFP-IRES-CreERT2 allele (Barker et al., 2007). This model has proved to be very useful for such studies, but selective silencing of the mutant allele consistently leads to a mosaic expression of the GFP and CreERT2 proteins in patches of crypts. Silencing is limited in the duodenum but is rather extensive in the distal small intestine. Homozygotes of this model cannot be used because of the perinatal mortality of Lgr5 pups (Morita et al., 2004). Additionally, studies have described Lgr5-DSRED-IRES-CreERT2 and Lgr5-DTReGFP bupropion hydrochloride (Tian et al., 2011) that make use of the specific expression pattern of Lgr5. However, these two models also abolish Lgr5 expression, preventing the generation of high-marker-expressing homozygous animals. Furthermore, the expression levels of Lgr5 are very low, which makes it challenging to use alternative techniques, such as in situ hybridization and immunohistochemistry, to visualize the stem cells (Kemper et al., 2012; Tian et al., 2011).
We previously generated a differential gene-expression profile for Lgr5 stem cells and their immediate daughters by GFP-based sorting of epithelial cells from isolated crypts of Lgr5-EGFP-ires-CreERT2 mice. When expression of individual genes was tested by in situ hybridization analysis, Olfm4 emerged as a highly specific and robust marker for Lgr5 stem cells. The highly stem cell-specific expression pattern of Olfm4 was also confirmed by single-molecule fluorescent in situ hybridization (Itzkovitz et al., 2012) and mass spectrometry (Muñoz et al., 2012). Although Olfm4 was not expressed in murine colon, human OLFM4 has been found to be enriched in both small intestinal and colonic crypts, as well as in subsets of colorectal carcinomas (van der Flier et al., 2009a).
The OLFM4 gene was originally cloned from human myeloblasts. It encodes for a 54 kDa protein of unknown function, which was predicted to be secreted (Zhang et al., 2002). Subsequently, it was shown that Xenopus ONT1, an Olfactomedin family member, acts as a BMP antagonist (Inomata et al., 2008). Additionally, an Olfm4 knockout mouse model was generated, which showed a function for Olfm4 in repressing the immune system to facilitate sustained Helicobacter pylori infection (Liu et al., 2010). In this context, Olfm4 was identified as an NFkB target. Loss of Olfm4 has been associated with progression of prostate cancer (Chen et al., 2011; Li et al., 2013) and Olfm4 was reported to be a Notch target in intestinal progenitor cells (VanDussen et al., 2012). Although the function and regulation of Olfm4 within the intestinal epithelium remain to be fully elucidated, the highly specific expression pattern of this gene in intestinal crypt stem cells prompted us to generate a knockin (KI) mouse line with the aim to generate a robust tool for visualization and gene modification in small intestinal stem cells.

A recent study indicated that

A recent study indicated that XIST expression can be lost upon prolonged passaging of female hiPSCs, referred to as “erosion of XCI” (Mekhoubad et al., 2012). This epigenetic erosion was found to be irreversible and correlated with a loss of differentiation characteristics and is very relevant for disease-modeling procedures. Erosion of XCI in hiPSC lines can be effectively prevented by XCR followed by XCI upon differentiation. Several studies have been published assessing XCR during the reprogramming process. Derepression attributed to XCR of genes located on the Xi has been observed in hESC lines (Lengner et al., 2010) and has been reported in studies involving gene expression profile comparison of multiple female hESC and hiPSC lines (Bruck and Benvenisty, 2011). Very recently, XCR was shown to happen efficiently early during reprogramming of human cells, but that this was quickly followed by initiation of XCI upon generation of nascent hiPSC lines, leading to XaXi cells only (Kim et al., 2014). These authors concluded that XCR was the result of overexpression of the exogenous reprogramming factors and that shutdown of the reprogramming cassette leads to XCI initiation. In contrast, our study indicates that in the present reprogramming and culture conditions, hiPSCs maintain the XaXa state in a high percentage of cells in the absence of ectopic expression of the reprogramming factors. The present single-cell allele-specific expression analysis revealed expression of the SUVAR39H1, HUWE1, ATP7A, NROB1, and G6PD phospholipase c inhibitor located at different positions on the X chromosome that was the Xi in the starting fibroblasts, in a high (>50%) proportion of cells of X12 and 47,XXX hiPSC lines. This effect was already present 20 days after transduction, arguing against erosion of XCI in our hiPSC lines and favoring XCR of the silenced Xi upon reprogramming. Our studies also phospholipase c inhibitor showed that XaXa cells represent the major population of cells at all stages after reprogramming, indicating that the present experimental conditions prevented robust precocious initiation of XCI, but allowed cells to maintain either the XaXa or the XaXi situation. The present findings would be in agreement with the suggestion that culturing hiPSCs in naive growth conditions facilitates XCR, which was not addressed in this initial report (Gafni et al., 2013). Indeed, our studies indicate that NHSM growth conditions effectuate a reduction in the percentage of cells with XIST-coated X chromosomes. However, this does not lead to changes in the allele-specific expression ratio of SUVAR39H1, HUWE1, ATP7A, and NROB1 in most hiPSC lines, and although we only analyzed our cells at an early stage after changing to the NHSM condition (passage 4), these findings suggest that XCR and XCI characteristics are hiPSC line specific and established during reprogramming and cannot be changed afterward. Recently, two other protocols have been described to revert primed into naive hESCs (Takashima et al., 2014; Theunissen et al., 2014). Surprisingly, one study reports initiation of XCI after induction of the naive state (Theunissen et al., 2014), whereas another study indicates loss of XIST and H3K27me3 accumulation after a reset of primed to naive ESCs (Takashima et al., 2014). These findings emphasize that knowledge about the transcriptional status of the X chromosomes in the ICM of the female preimplantation human embryo will be crucial to conclude which of these conditions result in hESCs that resemble ICM cells most.

Experimental Procedures

Author Contributions

Acknowledgments

Introduction
Adult stem cells (SCs) retain the capacity of self-renewal and differentiation to generate multiple differentiated cell types (Barker et al., 2007). Thus, these adult SCs are utilized to functionally regenerate damaged tissues or reverse organ failure (Yui et al., 2012). However, SCs that are deregulated during inflammation, infection, or tissue regeneration may turn into invasive cancer SCs (CSCs) (Beachy et al., 2004). Accordingly, tight spatial-temporal regulation of adult SC behaviors may confer injury resistance, tissue regeneration, or tumor suppression, whereas SC deregulation may cause tumor initiation and/or recurrence (Merlos-Suárez et al., 2011). However, the lack of molecular markers that reflect the fine modulation of SC homeostatic response to injury or regeneration significantly hinders the development of regenerative medicine and cancer therapy.

ARQ 621 Both numerical and experimental studies have shown that gluing the

Both numerical and experimental studies have shown that gluing the piezoelectric elements onto the beam only insignificantly affects the object\’s natural frequencies and eigenmodes. This allowed to generate a calculated estimation of the modal matrices based on the data obtained:

Next, the modal matrices and θ were determined experimentally in accordance with the proposed identification procedure. Each of the two columns of the matrix was obtained as a result of processing the ARQ 621 signals in the resonant modes generated by vibration of the piezoelectric stack actuator with the first and the second natural frequencies:

Then we were able to calculate the modal matrix T:

The modal matrix θ was determined by measuring the amplitude and phase of resonant vibrations of the beam\’s upper point using a laser vibrometer. The resonant modes with each of the natural frequencies were generated by an excitation from the first or the second actuator. The resulting matrix has the following form:

From here we can calculate the modal matrix F:

Next, we checked the quality of mode separation in accordance with the fourth step of the above-described identification procedure. The checking revealed that good separation of the modes was achieved both in measurements and in control. To illustrate the quality of mode separation, Fig. 4 shows different amplitude and frequency characteristics of an open-loop system in the frequency range containing two lower natural frequencies of the beam. To obtain the amplitude-frequency characteristic, the amplitude of the measured steady-state harmonic signal is divided by the amplitude of the harmonic ARQ 621 exciting signal . Fig. 4a shows the amplitude-frequency characteristics , obtained when the beam vibrations were excited by the ith actuator and the signal was measured by the jth sensor. It can be seen that each of these amplitude-frequency characteristics contains two pronounced resonant peaks, since each of the actuators excites, and each of the sensors responds to both the first and the second frequencies of the beam\’s vibrations.
Fig. 4b shows the amplitude–frequency characteristics of the open system, corresponding to the modal control loops. Here the beam was simultaneously excited by two actuators in the proportions given by the ith column of the matrix F, and the resulting signal was a combination of sensor signals with the coefficients given by the jth row of the matrix T. It can be seen that only the first resonant peak is present in the amplitude–frequency curve 11 corresponding to the first control loop, only the second peak is present in the amplitude–frequency curve 22 corresponding to the second loop, and resonant peaks are virtually absent in the amplitude–frequency curves 12 and 21 reflecting the mutual influence of the loops. This result indicates a high quality of separation of the first and second modes using modal matrices (8) and (9).
Within the framework of the experiment, we created a modal control system allowing to suppress the forced resonant vibrations of the beam with the first and second natural frequencies. For this purpose, the modal control law (4) was achieved in the controller:
where the diagonal structure of the matrix
provided separate control of the vibrations with the first and the second natural frequencies, and selection and adjustment of the transfer functions k1(s), k2(s) maintained the stability of the closed system and the most effective suppression of the vibrations at the corresponding resonant frequency. Fig. 5 illustrates the efficiency of the control system with an oscillogram of the vibration velocity of the upper end of the beam

The experiment was organized as follows. First, when the control system was switched off, resonant vibrations were induced in the beam by the vibration of the piezoelectric stack actuator: Fig. 5a corresponds to the resonance with the first natural frequency, Fig. 5b to the resonance with the second natural frequency. The system was then closed as shown in Fig. 2. The time when the control system was switched on can be clearly seen in Fig. 5. As a result, the amplitude of the beam\’s vibrations significantly decreased: the decrease was 79% for the first resonance and 88% for the second resonance.

Because a number of the causal determinants of

Because a number of the causal determinants of adverse infant outcomes associated with low SEP are potentially avoidable, strategies that promise even modest improvements warrant serious consideration. In a Cochrane Review (2015) examining randomized trials that compared midwifery-led continuity of care models to other care models for childbearing women, researchers found that midwifery care reduced the likelihood of preterm birth by 24% (Relative Risk 0.76, 95% CI: 0.64, 0.91) and fetal loss before 24 weeks gestation by 19% (RR 0.81, 95% CI: 0.67, 0.98) (Sandall, Soltani, Gates, Shennan, & Devane, 2015). If these findings are equally applicable for women of low SEP, whose infants are at the greatest risk of adverse outcomes, midwifery-led care may be an ideal model for vulnerable women.
Typically, physician-led care equates with the biomedical model of care. In this model the aim of prenatal care is to reduce risk of maternal fetal/infant morbidity and mortality through screening, diagnosis and treatment of complications as they arise (van Teijlingen, 2005). The biomedical model assumes a standardized approach to pregnancy and childbirth, with deviations from the norm often countered through medical intervention (Gregg, 1995). Though patient-centered care is encouraged within the biomedical model, the model is shaped by pathology and the underlying medical paradigm (Barry & Edgman-Levitan, 2012).
In contrast, midwifery practice specifically focuses on the mother׳s social, psychological, and cultural well-being, as well as the normal biological processes of pregnancy, birth and transition to parenthood (ten Hoope-Bender et al., 2014). A core buy SGC707 of the model, as defined in The Lancet Midwifery Series, includes capacity building to strengthen women׳s ability “to care for themselves and their families” (ten Hoope-Bender et al., 2014, p. 1227). Empowering patients as partners in health care requires mutual trust, and regard for the “woman׳s need for time, information, encouragement, validation and a supportive presence” (Kennedy, 2000, p. 10). Because of long appointment times and the model׳s relational emphasis, midwives are well positioned to understand and respond to contextual factors influencing patients’ behavior (Davis, 2010), such as personal autonomy, material and social resources, and individual abilities (Downe, Finlayson, Walsh, & Lavender, 2009). For low income women, practitioner–patient trust has been linked with clinician continuity, another hallmark of midwifery care (Phillippi & Avery, 2014), and has been associated with adherence to clinical advice (Sheppard, Zambrana, & O׳Malley, 2004). In addition, personalized continuity of care, in which a woman feels that her prenatal caregiver knows and remembers her and her health history from one visit to the next, has been shown to result in a three-fold increase in “very good” patient care ratings (Davey, Brown, & Bruinsma, 2005), which is especially important for women of low SEP who have reported lower levels of satisfaction in care compared to women of higher SEP (Haviland, Morales, Dial, & Pincus, 2005). All buy SGC707 of these elements of care: time, trusting relationship, and individualized care, along with emotional support, and the de-medicalization of pregnancy, have been identified as key attributes of quality prenatal care by women and care providers of all types (Sword et al., 2012). In addition, semiconservative replication is important to note that despite their names, either model, the biomedical model or midwifery model, can and has been adopted and delivered by various types of maternity providers. The attributes of midwifery care described here are not exclusive to the midwifery profession; it is a clinician׳s philosophy of care that determines his or her model of practice.
To date there has been no review of the literature examining birth outcomes of midwifery-led care compared to physician-led care for women of low SEP. The purpose of this scoping review is to identify all available information on this topic from the last 25 years, in order to present a summary of the “extent, range and nature” of the research, determine key gaps in the literature, and provide guidance for future studies (Arksey & O׳Malley, 2005, p. 6). This review will investigate if, in countries belonging to the Organization of Economic Co-operation and Development (OECD) (Organization of Economic Co-operation and Development (OECD), 2014), midwives’ patients of low socioeconomic position were at greater or lesser risk of adverse infant birth outcomes compared to physicians’ patients.

br Analysis Percentages were calculated

Analysis
Percentages were calculated for the SIP׳s 12 categories, two dimensions, independent categories not included in the two dimensions, and overall score. Results were examined for all patients with a physician diagnosis of narcolepsy, the subgroups with and without cataplexy, and the subgroups with and without HLA DQB1⁎0602 positivity. We conducted a two-way analysis of variance (ANOVA) to assess the difference in mean dysfunction scores according to cataplexy and HLA DQB1⁎0602. Linear regression was also used to assess the association between the SIP scores and cataplexy status and HLA status while controlling for age and sex. Associations between the SIP and the ESS and UNS were assessed with partial correlation coefficients from linear regression models of the entire sample, which included age, sex, and HLA DQB1⁎0602 status. Findings with p-values less than 0.05 were considered SIRT1/2 Inhibitor IV significant, and all testing was two-tailed. All analyses were conducted in Stata (version 10.0 for Macintosh, StataCorp, College Station, TX).

Results
Among 113 who SIRT1/2 Inhibitor IV did not have the HLA marker, 58 (51.3%) had cataplexy. Among 113 who were positive for the HLA marker, 94 (83.2%) had cataplexy. Figs. 1 and 2 show the mean unadjusted percent of full dysfunction for the total SIP score, two dimensions, and 12 categories. Scores are shown for: everyone, those with and without cataplexy restricted to patients without HLA DQB1⁎0602 (Fig. 1), and those with and without HLA DQB1⁎0602 positivity restricted to patients without cataplexy (Fig. 2). In the absence of HLA DQB1⁎0602, dysfunction was highest in those with cataplexy. In the absence of cataplexy, those with HLA DQB1⁎0602 have lower or similar dysfunction except for sleep and rest component of the SIP, in which the HLA DQB1⁎0602 allele was associated with a much higher level of dysfunction (Table 1).
In a two-way ANOVA, both cataplexy and HLA DQB1⁎0602 status were significantly and independently associated with total percent dysfunction (p<0.001 for both factors), total physical dysfunction (p<0.02 for cataplexy; p=0.05 for HLA DQB1⁎0602 allele), total psychological dysfunction (p<0.001 for both factors), and for other independent categories of dysfunction (p<0.001 for cataplexy; p=0.01 for HLA DQB1⁎0602 allele). In linear regression models with SIP scores as the dependent variable and age, sex, cataplexy and HLA status as the independent variables, those with cataplexy had higher scores than those without, and those with HLA DQB1⁎0602 positivity had lower scores than those without. Associations for cataplexy and HLA DQB1⁎0602 were statistically significant for both dimension and most of the categories (Table 2). Whether a patient had one (n=97) or two alleles (n=16) of HLA DQB1⁎0602 made little difference (data not shown). Those with cataplexy and without HLA DQB1⁎0602 positivity consistently showed the highest dysfunction (data not shown).
The 20 items most commonly endorsed by all patients are detailed in Table 2A, by those with cataplexy in Table 2B, and by those with HLA DQB1⁎0602 positivity in Table 2C. Considering all patients (Table 2A), 10 items were endorsed by at least a third of the patients, but only two concerned sleep. Tied for the third most commonly endorsed item was, “My sexual activity is decreased,” and tied for fourth was, “I forget a lot, for example, things that happened recently, where I put things, appointments.” The percent of men and women endorsing the item on sexual activity was not significantly different. Eighteen of the top 20 items were the same for all patients (Table 2A) and the two subgroups of those with cataplexy (Table 2B) and those with HLA DQB1⁎0602 positivity (Table 2C), although the order of items differed.
The partial correlation coefficients between the ESS and UNS and the SIP scores are presented in Table 3 controlling for age, sex, and HLA DQB1⁎0602 status. All correlations were significant. Correlations were stronger for the UNS than for the ESS for the total score, two dimensions and 11 of the 12 categories. As expected, the category with the strongest correlation with the ESS and UNS measures was Sleep and Rest, and the three categories with the weakest correlations were Ambulation, Communication, and Eating.