S BF.PLOS ONE | DOI:10.1371/journal.pone.0155923 June 17,21 /Digital Norm Enforcement

S BF.PLOS ONE | DOI:10.1371/journal.pone.0155923 June 17,21 /Digital Norm Enforcement in Online Firestorms
The vast streams of data that are produced by the use of automated digital services such as social media, email and mobile phones, also known as `Big Data’, have for some time been leveraged in the private sector to assist in tasks as diverse as logistics, targeted advertising and offering personalised multimedia content. More recently, these same data sources and methodologies have begun to be used to assist humanitarian and development organisations, allowing new ways to use data to implement, monitor and evaluate programs and policies [1]. ThePLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,1 /The International Postal Network and Other Global Flows as Proxies for National Wellbeingdefault.aspx); Postal Network data as used in the analysis is available as a Supporting Information file. Funding: Desislava Hristova received funding from the Project LASAGNE, Contract No. 318132 (STREP), funded by the European Commission and EPSRC Grant GALE (EP/K019392). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.ability of such novel data sources to complement traditional data collection techniques such as household surveys and focus groups is clear [2]. The data is collected passively without the need for costly and potentially dangerous active data collection, which also avoids inaccuracies due to human error, bias [3] or dishonesty. However, the use of Big Data for development is still relatively nascent and questions remain over the ability of such sources to measure or approximate metrics of interest. Invariably, data sources such as social networking applications enjoy deeper penetration in developed economies and rely on Peficitinib web expensive technologies such as smart phones and robust communications infrastructure. It has been noted that measurements of human dynamics based on such recent platforms can lead to strong biases [4], with worse implications for those with limited access to these digital platforms. In this paper we present analysis of a data source which is undoubtedly `Big’ yet represents one of the most established and pervasive long-distance communications networks in the history of mankind. The international postal network (IPN) established in 1874 is Bay 41-4109 dose administered by a dedicated United Nations specialised agency: the Universal Postal Union (UPU). Due to regulatory reporting requirements and the capabilities of automated data capture technologies such as RFID tags, the records of individual postal items maintained by UPU represent a rich record of human activity with unparalleled penetration, which can be expected to reflect individual level behaviour, local, regional and national economic activity and international economic relations. Network representations have emerged as an extremely powerful and general framework for analysing and modeling systems as diverse as transportation, biological processes, academic authorship and logistics among others [5]. Network science provides powerful tools for understanding such systems with large sets of coupled components with emergent behaviours more generally known as complex systems. Previous work has explored flows of both physical and digital nature, where physical flows of goods and people [6?2] and digital flows of information an.S BF.PLOS ONE | DOI:10.1371/journal.pone.0155923 June 17,21 /Digital Norm Enforcement in Online Firestorms
The vast streams of data that are produced by the use of automated digital services such as social media, email and mobile phones, also known as `Big Data’, have for some time been leveraged in the private sector to assist in tasks as diverse as logistics, targeted advertising and offering personalised multimedia content. More recently, these same data sources and methodologies have begun to be used to assist humanitarian and development organisations, allowing new ways to use data to implement, monitor and evaluate programs and policies [1]. ThePLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,1 /The International Postal Network and Other Global Flows as Proxies for National Wellbeingdefault.aspx); Postal Network data as used in the analysis is available as a Supporting Information file. Funding: Desislava Hristova received funding from the Project LASAGNE, Contract No. 318132 (STREP), funded by the European Commission and EPSRC Grant GALE (EP/K019392). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.ability of such novel data sources to complement traditional data collection techniques such as household surveys and focus groups is clear [2]. The data is collected passively without the need for costly and potentially dangerous active data collection, which also avoids inaccuracies due to human error, bias [3] or dishonesty. However, the use of Big Data for development is still relatively nascent and questions remain over the ability of such sources to measure or approximate metrics of interest. Invariably, data sources such as social networking applications enjoy deeper penetration in developed economies and rely on expensive technologies such as smart phones and robust communications infrastructure. It has been noted that measurements of human dynamics based on such recent platforms can lead to strong biases [4], with worse implications for those with limited access to these digital platforms. In this paper we present analysis of a data source which is undoubtedly `Big’ yet represents one of the most established and pervasive long-distance communications networks in the history of mankind. The international postal network (IPN) established in 1874 is administered by a dedicated United Nations specialised agency: the Universal Postal Union (UPU). Due to regulatory reporting requirements and the capabilities of automated data capture technologies such as RFID tags, the records of individual postal items maintained by UPU represent a rich record of human activity with unparalleled penetration, which can be expected to reflect individual level behaviour, local, regional and national economic activity and international economic relations. Network representations have emerged as an extremely powerful and general framework for analysing and modeling systems as diverse as transportation, biological processes, academic authorship and logistics among others [5]. Network science provides powerful tools for understanding such systems with large sets of coupled components with emergent behaviours more generally known as complex systems. Previous work has explored flows of both physical and digital nature, where physical flows of goods and people [6?2] and digital flows of information an.

Lar strain magnitudes (22.8 ) also up-regulated the mRNA level of the hyaluronidases

Lar strain magnitudes (22.8 ) also up-regulated the mRNA level of the hyaluronidases HYAL1 and HYAL2 after 6 and 12 h of loading respectively, which cleave hyaluronan [75]. Pro-inflammatory Factors. Two pivotal pro-inflammatory enzymes in cartilage are the inducible nitric oxide synthase (iNOS) and the cyclooxygenase-2 (COX-2). They induce proinflammatory actions through the production of nitric oxide (NO) and prostaglandin E2 (PGE2). Several studies showed that there was no effect of CTS on the iNOS and COX-2 mRNA expression and on their products NO and PGE2 when the loading was applied at a frequency of 0.05 Hz [20,27,48,52,53,76,77] (Table 7). Only one study found an increase in iNOS and NO at 0.05 Hz [76]. However, higher frequencies (0.17 and 0.5 Hz) up-regulated especially COX-2 and with increasing loading duration also iNOS, NO and PGE2 [26,28,36,37,47]. Matsukawa et al. (2004) reported that CTS stimulated iNOS mRNA only on fibronectin coated culture plates, but not on collagen coating. Furthermore, NO was up-regulated after CTS when the culture plates were coated with fibronectin, whereas NO production was down-regulated on collagen I coating [47]. The exposure of chondrocytes to the pro-inflammatory cytokines IL1- and TNF- up-regulated the matrix degrading proteases MMP-1, MMP-9, MMP-13, the pro-inflammatory enzymes iNOS and COX-2, and their products NO and PGE2 [27,29,53,76]. Furthermore, IL-1 suppressed cell proliferation [32]. It is thought that IL1- and TNF- play an important role inPLOS ONE | DOI:10.1371/journal.pone.0119816 March 30,15 /Cyclic Tensile Strain and Chondrocyte MetabolismTable 6. Effects of CTS on proteases. Frequency 0.05 Hz 0.5 Hz Loading duration 4?8 h 1h 3h 6h 12 h Strain magnitude 6 10 7 10 7 7 10 16 23 24 h 7 10 16 36 h 48 h 1 Hz 0.5 h 7 16 7.5 ” “a ” ” ” ” “a “a a ” ” ” ” ” ” MMP-1 ” MMP-3 MMP-9 MMP-13 ADAMTS-4 ADAMTS-5 Reference [27,53] [37] [38] [37] [38] [38] [37] [26] [34] [38] [37] [26] [38] [26] [46]Effects of CTS on proteases relative to unloaded controls, sorted by loading frequency mRNA levels of loaded cells were unchanged relative to unloaded cellsa” mRNA levels of loaded cells were increased relative to unloaded cells mRNA levels measured after a 4 h recovery instead of immediately after the get EPZ-5676 loadingdoi:10.1371/journal.pone.0119816.tthe development of osteoarthritis [71,78]. Two studies showed that IL-1 was not (S)-(-)-Blebbistatin structure influenced by CTS of 7 for 12 h [38,57]. However, when loading continued up to 24 h or when the strain magnitude was increased (21?3 ) IL-1 and TNF- were significantly up-regulated [34,38,57,75]. Beneficial Effect of CTS in an Already Inflamed Environment. To investigate the beneficial potential of CTS in an inflamed environment, cells were exposed to IL-1 or TNF- and CTS, simultaneously. Interestingly, CTS at strain magnitudes between 3 and 10 and a frequency of 0.05 Hz led to the suppression of IL-1 and TNF- induced inflammatory effects already after 60 min [20,76]. Furthermore, 4 and 24 h of loading counteracted the IL-1 and TNF- induced MMP-1, COX-2, and iNOS expression, the production of NO, and the synthesis of PGE2 [27,53,76]. The suppression was evident for strains between 2?0 , whereas the strongest effect was observed at 6 strain [27]. CTS of 12 , 15 and 18 strain, however, had no inhibitory effect on IL-1 induced iNOS expression and NO production [76]. Even more, under these higher strain magnitudes cells produced more NO and elevated.Lar strain magnitudes (22.8 ) also up-regulated the mRNA level of the hyaluronidases HYAL1 and HYAL2 after 6 and 12 h of loading respectively, which cleave hyaluronan [75]. Pro-inflammatory Factors. Two pivotal pro-inflammatory enzymes in cartilage are the inducible nitric oxide synthase (iNOS) and the cyclooxygenase-2 (COX-2). They induce proinflammatory actions through the production of nitric oxide (NO) and prostaglandin E2 (PGE2). Several studies showed that there was no effect of CTS on the iNOS and COX-2 mRNA expression and on their products NO and PGE2 when the loading was applied at a frequency of 0.05 Hz [20,27,48,52,53,76,77] (Table 7). Only one study found an increase in iNOS and NO at 0.05 Hz [76]. However, higher frequencies (0.17 and 0.5 Hz) up-regulated especially COX-2 and with increasing loading duration also iNOS, NO and PGE2 [26,28,36,37,47]. Matsukawa et al. (2004) reported that CTS stimulated iNOS mRNA only on fibronectin coated culture plates, but not on collagen coating. Furthermore, NO was up-regulated after CTS when the culture plates were coated with fibronectin, whereas NO production was down-regulated on collagen I coating [47]. The exposure of chondrocytes to the pro-inflammatory cytokines IL1- and TNF- up-regulated the matrix degrading proteases MMP-1, MMP-9, MMP-13, the pro-inflammatory enzymes iNOS and COX-2, and their products NO and PGE2 [27,29,53,76]. Furthermore, IL-1 suppressed cell proliferation [32]. It is thought that IL1- and TNF- play an important role inPLOS ONE | DOI:10.1371/journal.pone.0119816 March 30,15 /Cyclic Tensile Strain and Chondrocyte MetabolismTable 6. Effects of CTS on proteases. Frequency 0.05 Hz 0.5 Hz Loading duration 4?8 h 1h 3h 6h 12 h Strain magnitude 6 10 7 10 7 7 10 16 23 24 h 7 10 16 36 h 48 h 1 Hz 0.5 h 7 16 7.5 ” “a ” ” ” ” “a “a a ” ” ” ” ” ” MMP-1 ” MMP-3 MMP-9 MMP-13 ADAMTS-4 ADAMTS-5 Reference [27,53] [37] [38] [37] [38] [38] [37] [26] [34] [38] [37] [26] [38] [26] [46]Effects of CTS on proteases relative to unloaded controls, sorted by loading frequency mRNA levels of loaded cells were unchanged relative to unloaded cellsa” mRNA levels of loaded cells were increased relative to unloaded cells mRNA levels measured after a 4 h recovery instead of immediately after the loadingdoi:10.1371/journal.pone.0119816.tthe development of osteoarthritis [71,78]. Two studies showed that IL-1 was not influenced by CTS of 7 for 12 h [38,57]. However, when loading continued up to 24 h or when the strain magnitude was increased (21?3 ) IL-1 and TNF- were significantly up-regulated [34,38,57,75]. Beneficial Effect of CTS in an Already Inflamed Environment. To investigate the beneficial potential of CTS in an inflamed environment, cells were exposed to IL-1 or TNF- and CTS, simultaneously. Interestingly, CTS at strain magnitudes between 3 and 10 and a frequency of 0.05 Hz led to the suppression of IL-1 and TNF- induced inflammatory effects already after 60 min [20,76]. Furthermore, 4 and 24 h of loading counteracted the IL-1 and TNF- induced MMP-1, COX-2, and iNOS expression, the production of NO, and the synthesis of PGE2 [27,53,76]. The suppression was evident for strains between 2?0 , whereas the strongest effect was observed at 6 strain [27]. CTS of 12 , 15 and 18 strain, however, had no inhibitory effect on IL-1 induced iNOS expression and NO production [76]. Even more, under these higher strain magnitudes cells produced more NO and elevated.

Ed by CD4+CD25+Foxp3+ Treg.10,13,37 In addition to CD4+ Treg

Ed by CD4+CD25+Foxp3+ Treg.10,13,37 In addition to CD4+ Treg, an immunosuppressive subset of CD8+ intraepithelial lymphocytes found in the small intestine was found to express fgl2 mRNA.38 Furthermore, Li et al. recently demonstrated in a rat cardiac transplant model that tolerogenic CD8+CD45RClow Treg expressed high levels of fgl2 mRNA compared to na e CD8+ Treg.39 A list of these FGL2-expressing Treg and their properties is shown in Table 2. In an early report, we demonstrated that FGL2 directly inhibits T cell proliferation in response to various stimuli (alloantigen, ConA, and anti-CD3/ anti-CD28 mAbs) and promotes a Th2 response. Furthermore, FGL2 was found to inhibit the maturation of bone marrow-derived DC (BMDC), reducing their ability to stimulate T cells in mixed purchase Wuningmeisu C lymphocyte reaction (MLR) co-cultures.40 In order to elucidate further the role of FGL2, we generated mice with a targeted deletion of fgl2 (fgl2-/-) and found that these mice have increased T cell, B cell, and DC reactivity compared to fgl2+/+ wild-type mice (Figure 2).13 Furthermore, Treg isolated from fgl2-/mice had impaired ability to suppress effector T cell proliferation. The fgl2-/- mice also develop autoimmune glomerulonephritis as they age, likely related to the state of immune activation.Figure 2. Immunoregulatory Function of FGL2. Mice deficient in FGL2 (fgl2-/-) have enhanced T cell, B cell, and DC function as shown in the figure. The fgl2-/- mice develop autoimmune glomerulonephritis as they age reflective of chronic immune activation. DC, dendritic cell; LPS, lipopolysaccharide.Rambam Maimonides Medical JournalJuly 2015 Volume 6 Issue 3 eTreg and FGL2 in Alloimmunity and AutoimmunityTable 2. FGL2-expressing Regulatory T Cells. Molecule TCR Co-receptor CD8 , MHC-I/II restricted CD8+CD45RClow , MHC-I restricted DNT cells CD4+Foxp3+, MHC-II restricted , MHC-II-restricted Absent CDCD8 CD8 Small subset express CD4 or CD8 Lin-cells in intestinal epithelium, cryptopatches Thymus (induced IEL from conventional T cells) Thymus-independent Self-antigen, foreign antigen, oligoclonal CD69, FasL, granzymes, CD122, B220, NK-Like receptors Negative for CD2, CD5, CD28, LFA-1, mostly Thy1-negative Low CD5 in intestine, TGF-3, LAG-3, FGL2 Homeostasis in intestine (food and microbes in lamina propria) More common in the small intestine Inhibitory NK receptors CD8 PD168393 web recruitment of LAT and LCK from the TCR CD45RClow, Foxp3, GITR, IL-10, and IL13 UnknownOriginThymus, peripheryThymusDevelopmentCD40-Ig treatmentThymus-dependent Thymus (tTreg) (DC+, IL-12+, IL-15), Induced in the thymus-independent periphery (pTreg) Polyclonal CD25, CD28, FasL, perforin, CTLA-4 Negative for NK1.1, Foxp3 CD25high, GITR, CTLA4, OX-40, TIGIT, CD39/CD73, IL-35, PD-1, GzmbSpecificity MarkersCytokine expression Target cell/ specializationIFN-, IDO, FGL2 Interaction with plasmacytoid DC to suppress CD4+ T cell activity Accumulated in the graft and spleen Contact-dependentFGL2-mediated suppression of T cell proliferation Contact-independent IDO-mediated suppressionFGL2, IFN- (not IL2) LPS-activated DC CD8 and CD4 T cells Mature and immature DC B cells Trogocytosis and CD8+ T cell (FasL) mediated killing CTLA-4 dependent downregulation of DC activation DC apoptosis through Fas:FasLIL-10, TGF-, FGL2 DC T cellsMechanismsDC inhibition by sequestration of CD80/CD86 T cell deprivation of IL-2 Inhibition of DC maturation Adenosine inhibition, impeding T cell effector and DC activity Anti-inflammatory Inductio.Ed by CD4+CD25+Foxp3+ Treg.10,13,37 In addition to CD4+ Treg, an immunosuppressive subset of CD8+ intraepithelial lymphocytes found in the small intestine was found to express fgl2 mRNA.38 Furthermore, Li et al. recently demonstrated in a rat cardiac transplant model that tolerogenic CD8+CD45RClow Treg expressed high levels of fgl2 mRNA compared to na e CD8+ Treg.39 A list of these FGL2-expressing Treg and their properties is shown in Table 2. In an early report, we demonstrated that FGL2 directly inhibits T cell proliferation in response to various stimuli (alloantigen, ConA, and anti-CD3/ anti-CD28 mAbs) and promotes a Th2 response. Furthermore, FGL2 was found to inhibit the maturation of bone marrow-derived DC (BMDC), reducing their ability to stimulate T cells in mixed lymphocyte reaction (MLR) co-cultures.40 In order to elucidate further the role of FGL2, we generated mice with a targeted deletion of fgl2 (fgl2-/-) and found that these mice have increased T cell, B cell, and DC reactivity compared to fgl2+/+ wild-type mice (Figure 2).13 Furthermore, Treg isolated from fgl2-/mice had impaired ability to suppress effector T cell proliferation. The fgl2-/- mice also develop autoimmune glomerulonephritis as they age, likely related to the state of immune activation.Figure 2. Immunoregulatory Function of FGL2. Mice deficient in FGL2 (fgl2-/-) have enhanced T cell, B cell, and DC function as shown in the figure. The fgl2-/- mice develop autoimmune glomerulonephritis as they age reflective of chronic immune activation. DC, dendritic cell; LPS, lipopolysaccharide.Rambam Maimonides Medical JournalJuly 2015 Volume 6 Issue 3 eTreg and FGL2 in Alloimmunity and AutoimmunityTable 2. FGL2-expressing Regulatory T Cells. Molecule TCR Co-receptor CD8 , MHC-I/II restricted CD8+CD45RClow , MHC-I restricted DNT cells CD4+Foxp3+, MHC-II restricted , MHC-II-restricted Absent CDCD8 CD8 Small subset express CD4 or CD8 Lin-cells in intestinal epithelium, cryptopatches Thymus (induced IEL from conventional T cells) Thymus-independent Self-antigen, foreign antigen, oligoclonal CD69, FasL, granzymes, CD122, B220, NK-Like receptors Negative for CD2, CD5, CD28, LFA-1, mostly Thy1-negative Low CD5 in intestine, TGF-3, LAG-3, FGL2 Homeostasis in intestine (food and microbes in lamina propria) More common in the small intestine Inhibitory NK receptors CD8 recruitment of LAT and LCK from the TCR CD45RClow, Foxp3, GITR, IL-10, and IL13 UnknownOriginThymus, peripheryThymusDevelopmentCD40-Ig treatmentThymus-dependent Thymus (tTreg) (DC+, IL-12+, IL-15), Induced in the thymus-independent periphery (pTreg) Polyclonal CD25, CD28, FasL, perforin, CTLA-4 Negative for NK1.1, Foxp3 CD25high, GITR, CTLA4, OX-40, TIGIT, CD39/CD73, IL-35, PD-1, GzmbSpecificity MarkersCytokine expression Target cell/ specializationIFN-, IDO, FGL2 Interaction with plasmacytoid DC to suppress CD4+ T cell activity Accumulated in the graft and spleen Contact-dependentFGL2-mediated suppression of T cell proliferation Contact-independent IDO-mediated suppressionFGL2, IFN- (not IL2) LPS-activated DC CD8 and CD4 T cells Mature and immature DC B cells Trogocytosis and CD8+ T cell (FasL) mediated killing CTLA-4 dependent downregulation of DC activation DC apoptosis through Fas:FasLIL-10, TGF-, FGL2 DC T cellsMechanismsDC inhibition by sequestration of CD80/CD86 T cell deprivation of IL-2 Inhibition of DC maturation Adenosine inhibition, impeding T cell effector and DC activity Anti-inflammatory Inductio.

As acquired for anatomic reference (magnetization-prepared rapid gradient echo (MPRAGE); TR

As acquired for anatomic reference (magnetization-prepared rapid gradient echo (MPRAGE); TR/TE/inversion time = 2,300/3.93/1,100 ms, flip angle = 12? 256 ?256 matrix, 1 mm isotropic voxels).Figure 2. (a) Example of magnetic resonance spectroscopy (1H-MRS) voxel placement in the left substantia nigra (SN; 13 ?13 ?13 mm) overlaid on an axial magnetization transfer contrast image. Insert shows the midbrain without the 1H-MRS voxel. Images are displayed in neurological convention. (b) Sample 1H-MRS spectrum obtained from the left SN; the black line is a spectrum (640 averages), the red line is an overlay of the spectral fit. Cho, choline; Cr, creatine; Glx, glutamate+glutamine; NAA, N-acetyl-aspartate. (c) Glx in the left SN in healthy controls and patients with schizophrenia. Horizontal lines indicate group means.Figure 1. (a) Participants selected either a large reward of 30?or a smaller reward of 10?by pushing a right or left box. Although the probability of receiving 10?remained constant at 0.9, the probability of receiving 30?varied between runs (0.1, 0.33, or 0.9). After the first 10 trials of each run, participants developed an expected value (EV) (probability ?reward magnitude (RM)) of their choice. Prediction error (PE) was calculated as the difference between RM and EV for each trial (that is, if EV = 9?(0.9 ?10?, but RM = 0? then PE = – 9). (b) Three conditions were presented. During Decision, subjects selected the left or right box corresponding to a 10?or 30?choice. For a given run, the left/right position of the 10?30?choice did not change. During Decision Display, the color of the box selected changed, indicating that a response was made. Feedback was received during Reward Presentation (RM of 0? 10? or 30?.npj Schizophrenia (2015) 14001 ?2015 Schizophrenia International Research Group/Nature Publishing GroupSN glutamate and prediction error in schizophrenia DM White et alvariables. A general linear model was used to determine whether HC and SZ performed the task in a similar manner. Each participant’s response during every trial was binarized to indicate a left or a right button press. These values were entered as the dependent variable in a linear regression. Fixed independent factors were entered to define each of the six sessions and each of the 25 trials. Group was entered as a random factor and participant identification was entered as a covariate. A planned contrast was conducted for the outcome of diagnostic status as a predictor of trial response. regressor was orthogonalized to the reward presentation to ensure it was uniquely specified and LT-253 mechanism of action validly estimated.23 Contrasts were carried buy Quinagolide (hydrochloride) forward to the second level for within- and between-group analyses. Whole-brain analyses were corrected for multiple comparisons using false discovery rate with significance level set to Po0.01. In addition, we conducted region of interest analyses using masks from the WFU pickatlas24 for the midbrain/SN (TD lobes) and bilateral ventral striatum/nucleus accumbens (IBASPM 71). The significance level was set to Po0.05 using small-volume corrections (SVC).fMRIData were analyzed using SPM8 (Wellcome Trust, London, UK). Preprocessing included slice-timing correction, realignment, artifact and motion correction using ArtRepair, coregistration to the structural scan, normalization to Montreal Neurological Institute space, and smoothing (4 mm) using DARTEL.22 First-level analyses were conducted for each participant with a general linear model t.As acquired for anatomic reference (magnetization-prepared rapid gradient echo (MPRAGE); TR/TE/inversion time = 2,300/3.93/1,100 ms, flip angle = 12? 256 ?256 matrix, 1 mm isotropic voxels).Figure 2. (a) Example of magnetic resonance spectroscopy (1H-MRS) voxel placement in the left substantia nigra (SN; 13 ?13 ?13 mm) overlaid on an axial magnetization transfer contrast image. Insert shows the midbrain without the 1H-MRS voxel. Images are displayed in neurological convention. (b) Sample 1H-MRS spectrum obtained from the left SN; the black line is a spectrum (640 averages), the red line is an overlay of the spectral fit. Cho, choline; Cr, creatine; Glx, glutamate+glutamine; NAA, N-acetyl-aspartate. (c) Glx in the left SN in healthy controls and patients with schizophrenia. Horizontal lines indicate group means.Figure 1. (a) Participants selected either a large reward of 30?or a smaller reward of 10?by pushing a right or left box. Although the probability of receiving 10?remained constant at 0.9, the probability of receiving 30?varied between runs (0.1, 0.33, or 0.9). After the first 10 trials of each run, participants developed an expected value (EV) (probability ?reward magnitude (RM)) of their choice. Prediction error (PE) was calculated as the difference between RM and EV for each trial (that is, if EV = 9?(0.9 ?10?, but RM = 0? then PE = – 9). (b) Three conditions were presented. During Decision, subjects selected the left or right box corresponding to a 10?or 30?choice. For a given run, the left/right position of the 10?30?choice did not change. During Decision Display, the color of the box selected changed, indicating that a response was made. Feedback was received during Reward Presentation (RM of 0? 10? or 30?.npj Schizophrenia (2015) 14001 ?2015 Schizophrenia International Research Group/Nature Publishing GroupSN glutamate and prediction error in schizophrenia DM White et alvariables. A general linear model was used to determine whether HC and SZ performed the task in a similar manner. Each participant’s response during every trial was binarized to indicate a left or a right button press. These values were entered as the dependent variable in a linear regression. Fixed independent factors were entered to define each of the six sessions and each of the 25 trials. Group was entered as a random factor and participant identification was entered as a covariate. A planned contrast was conducted for the outcome of diagnostic status as a predictor of trial response. regressor was orthogonalized to the reward presentation to ensure it was uniquely specified and validly estimated.23 Contrasts were carried forward to the second level for within- and between-group analyses. Whole-brain analyses were corrected for multiple comparisons using false discovery rate with significance level set to Po0.01. In addition, we conducted region of interest analyses using masks from the WFU pickatlas24 for the midbrain/SN (TD lobes) and bilateral ventral striatum/nucleus accumbens (IBASPM 71). The significance level was set to Po0.05 using small-volume corrections (SVC).fMRIData were analyzed using SPM8 (Wellcome Trust, London, UK). Preprocessing included slice-timing correction, realignment, artifact and motion correction using ArtRepair, coregistration to the structural scan, normalization to Montreal Neurological Institute space, and smoothing (4 mm) using DARTEL.22 First-level analyses were conducted for each participant with a general linear model t.

Having had an episode of URTI in the last month increased

Having had an episode of URTI in the last month increased the odds of colonization with a low-invasive serotypes. Carriage of low-(R)-K-13675 chemical information invasiveness serotypes also varied over time, with a lower prevalence in the period from February to June (Table 2). Being white was associated with a lower odds of colonization with a low invasiveness serotype compared with mixed race children. However, these differences in effect sizes for the high and low invasiveness serotypes were not statistically significant.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptVaccine. Author manuscript; available in PMC 2017 February 03.Menezes et al.PageSerotype Distribution and Antibiotic susceptibilityAuthor Manuscript Author ManuscriptGenotypingTable 3 shows the distribution of serotypes recovered throughout the period of the study. The most prevalent serotypes were 6A/B (25.4 ), 19F (10.1 ) and, 14 (9.0 ). The serotypes included in PCV10 and PCV13 accounted for 52.2 and 55.5 , respectively. The most frequent non-vaccine serotypes were 16F (4.8 ), 15B/C (4.5 ), 6C/D (3.5 ), 34 (3 ) and not typeable (7.3 ); 15.3 (61/398) of the isolates of S. pneumoniae did not have the capsular type determined by multiplex-PCR. We did not find any fluctuation in the distribution of serotypes during the study period. Overall, 38.4 (153/398) of the pneumococci were non-susceptible to penicillin, with MICs ranging from 0.12 to 8.0 /ml. The percentage of capsular types included in the PCV10 vaccine among penicillin non-susceptible accounted for 73.2 (112/153) as follows: 6A/B (45/112; 40 ), 19F (29/112; 25.9 ), 14 (20/112; 18 ), 23F (12/112; 11 ) and 3-MA web others (6/112; 5 ). The non-vaccine serotypes commonly associated with penicillin nonsusceptibility (41/153; 22 ) were: NT (6/41; 14.6 ), 16F (4/41; 9.8 ), 13 (3/41; 7.3 ), 21 (3/41; 7.3 ), 34 (1/41; 2.4 ). In addition, 58 (231/398) were non-susceptible to TMP/ SMX, 18.6 (74/398) to tetracycline, 3 (12/398) to erythromycin, and 2 (8/398) to cefotaxime. Of the 153 penicillin non-susceptible isolates, 113 (73.8 ) were also non susceptible to TMP/SMX. The drugs involved in the most frequently identified patterns of multidrug nonsusceptibility, defined as being intermediate or resistant to three or more classes of antibiotics, were penicillin, TMP/SMX and tetracycline (14 of 398 isolates), penicillin, TMP/SMX and erythromycin (7 of 398 isolates), penicillin, TMP/SMX, cefotaxime (3 of 398 isolates) and penicillin, TMP/SMX, cefotaxime, and erythromycin (3 of 398 isolates).Author Manuscript Author ManuscriptPFGE analysis confirmed that 24 of the 156 (15.4 ) children were highly likely to have been colonized by the same pneumococcal PFGE type at multiple time points: 6A/B (n=9/24; 37.5 ), 14 (n=5/24; 20.8 ), 19F (n=4/24; 16.7 ), 34 (n=2/24; 8.3 ), 23F (n=1/24; 4.2 ), 3 (n=1/24; 4.2 ), 6C (n=1/24; 4.2 ) and 15B/C (n=1/24; 4.2 ). The most commonly identified sequence types were ST156 (14;[n=5]), ST 66 (14;[n=10]), ST177 (19F; [n=7]), ST 338 (23F;[n=6]), ST 3930 (6C; [n=3]) and ST 771 (34; [n=4]). Strains belonging to the ST 66, ST 156 and ST 177 were isolated more than once in the same child, indicating persistence in the environment for up to six months.DiscussionWe found carriage prevalence of 55 with temporal fluctuations, with lower prevalence of carriage occurring in the period from February to June. Temporal variation was not observed in a previous study conducted in England in a period of ten months [19] but was.Having had an episode of URTI in the last month increased the odds of colonization with a low-invasive serotypes. Carriage of low-invasiveness serotypes also varied over time, with a lower prevalence in the period from February to June (Table 2). Being white was associated with a lower odds of colonization with a low invasiveness serotype compared with mixed race children. However, these differences in effect sizes for the high and low invasiveness serotypes were not statistically significant.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptVaccine. Author manuscript; available in PMC 2017 February 03.Menezes et al.PageSerotype Distribution and Antibiotic susceptibilityAuthor Manuscript Author ManuscriptGenotypingTable 3 shows the distribution of serotypes recovered throughout the period of the study. The most prevalent serotypes were 6A/B (25.4 ), 19F (10.1 ) and, 14 (9.0 ). The serotypes included in PCV10 and PCV13 accounted for 52.2 and 55.5 , respectively. The most frequent non-vaccine serotypes were 16F (4.8 ), 15B/C (4.5 ), 6C/D (3.5 ), 34 (3 ) and not typeable (7.3 ); 15.3 (61/398) of the isolates of S. pneumoniae did not have the capsular type determined by multiplex-PCR. We did not find any fluctuation in the distribution of serotypes during the study period. Overall, 38.4 (153/398) of the pneumococci were non-susceptible to penicillin, with MICs ranging from 0.12 to 8.0 /ml. The percentage of capsular types included in the PCV10 vaccine among penicillin non-susceptible accounted for 73.2 (112/153) as follows: 6A/B (45/112; 40 ), 19F (29/112; 25.9 ), 14 (20/112; 18 ), 23F (12/112; 11 ) and others (6/112; 5 ). The non-vaccine serotypes commonly associated with penicillin nonsusceptibility (41/153; 22 ) were: NT (6/41; 14.6 ), 16F (4/41; 9.8 ), 13 (3/41; 7.3 ), 21 (3/41; 7.3 ), 34 (1/41; 2.4 ). In addition, 58 (231/398) were non-susceptible to TMP/ SMX, 18.6 (74/398) to tetracycline, 3 (12/398) to erythromycin, and 2 (8/398) to cefotaxime. Of the 153 penicillin non-susceptible isolates, 113 (73.8 ) were also non susceptible to TMP/SMX. The drugs involved in the most frequently identified patterns of multidrug nonsusceptibility, defined as being intermediate or resistant to three or more classes of antibiotics, were penicillin, TMP/SMX and tetracycline (14 of 398 isolates), penicillin, TMP/SMX and erythromycin (7 of 398 isolates), penicillin, TMP/SMX, cefotaxime (3 of 398 isolates) and penicillin, TMP/SMX, cefotaxime, and erythromycin (3 of 398 isolates).Author Manuscript Author ManuscriptPFGE analysis confirmed that 24 of the 156 (15.4 ) children were highly likely to have been colonized by the same pneumococcal PFGE type at multiple time points: 6A/B (n=9/24; 37.5 ), 14 (n=5/24; 20.8 ), 19F (n=4/24; 16.7 ), 34 (n=2/24; 8.3 ), 23F (n=1/24; 4.2 ), 3 (n=1/24; 4.2 ), 6C (n=1/24; 4.2 ) and 15B/C (n=1/24; 4.2 ). The most commonly identified sequence types were ST156 (14;[n=5]), ST 66 (14;[n=10]), ST177 (19F; [n=7]), ST 338 (23F;[n=6]), ST 3930 (6C; [n=3]) and ST 771 (34; [n=4]). Strains belonging to the ST 66, ST 156 and ST 177 were isolated more than once in the same child, indicating persistence in the environment for up to six months.DiscussionWe found carriage prevalence of 55 with temporal fluctuations, with lower prevalence of carriage occurring in the period from February to June. Temporal variation was not observed in a previous study conducted in England in a period of ten months [19] but was.

E the ways in which negotiations for the care of AIDS

E the ways in which negotiations for the care of AIDS orphans utilizes the cultural logics of bridewealth and patrilineality in order to justify a range of configurations of care.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptSituating caregiving: fostering, migrant labour, and marriageLike many of the grandmothers I spoke with, ‘M’e Matau lived with her own maternal grandmother from early childhood until she was 15 years old. She was sent by her parents to provide companionship and to assist her grandmother with household chores. Basotho like ‘M’e Matau use what they know about fostering from their own experiences and adapt it to accommodate shifting domestic arrangements stemming from the GW9662 custom synthesis increase in the number of orphans. While this recent increase is perhaps more dramatic owing to the severity and scale of the AIDS pandemic, caregiving practices, including child fostering, have always been in flux, shifting in response to LY317615 cost historical and political-economic circumstances. In this section, I situate long-standing child fostering practices that serve as the basis for the contemporary movement of AIDS orphans, and trace the legal and historical processes that have impacted these practices, with a focus on migrant labour and marriage. Child fostering has been widely studied across the African continent (Bledsoe 1989; Goody 1982; Madhavan 2004; Renne 1993). It is typically characterized by the movement of children for a variety of purposes related to health, fertility, social responsibility, caregiving relationships, apprenticeship, and educational opportunities. Despite numerous characterizations of fostering as fundamentally reciprocal in nature (Bledsoe 1989), such practices are not always beneficial or voluntary. Several scholars have highlighted the role that poverty plays in the circulation of children, often transferring the productive contributions of children from one household to another (Goody 1982; Leinaweaver 2007; Schrauwers 1999). Thus, processes that shape social relationships are not always unambiguously positive, alliance-building strategies, but may also be necessitated by poverty, inequality, and disease. Child fostering has a long history in Lesotho as a regular strategy for sharing responsibility and supporting and connecting kin (Murray 1981; Page 1989). In Lesotho, HIV/AIDS has been a major factor in changing fostering patterns, as it has elsewhere in sub-Saharan Africa. 4 Household migration has been an important coping strategy employed by children and families impacted by AIDS (Ansell van Blerk 2004). Although orphans are still predominantly cared for within the family, researchers worry that family and communitybased networks of care are becoming saturated (Abebe Aase 2007; Courtney Iwaniec 2009; L. Townsend Dawes 2004). Others also note that increased pressure on caregivers has resulted in some children receiving inadequate care, as caregivers struggle to meet these children’s needs, whether financial (Ansell van Blerk 2004; Kidman, Petrow Heymann 2007) or emotional and psycho-social (Ansell Young 2004; Nyesigomwe 2005). The emergence and uncertainty of matrilocal care must be understood as embedded in a context4UNICEF (2010) estimates that there are 110,000?20,000 AIDS orphans in Lesotho; of these children, 12,000 are HIV-positive. J R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPagethat is constrained not only by AIDS and poverty but also by a varie.E the ways in which negotiations for the care of AIDS orphans utilizes the cultural logics of bridewealth and patrilineality in order to justify a range of configurations of care.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptSituating caregiving: fostering, migrant labour, and marriageLike many of the grandmothers I spoke with, ‘M’e Matau lived with her own maternal grandmother from early childhood until she was 15 years old. She was sent by her parents to provide companionship and to assist her grandmother with household chores. Basotho like ‘M’e Matau use what they know about fostering from their own experiences and adapt it to accommodate shifting domestic arrangements stemming from the increase in the number of orphans. While this recent increase is perhaps more dramatic owing to the severity and scale of the AIDS pandemic, caregiving practices, including child fostering, have always been in flux, shifting in response to historical and political-economic circumstances. In this section, I situate long-standing child fostering practices that serve as the basis for the contemporary movement of AIDS orphans, and trace the legal and historical processes that have impacted these practices, with a focus on migrant labour and marriage. Child fostering has been widely studied across the African continent (Bledsoe 1989; Goody 1982; Madhavan 2004; Renne 1993). It is typically characterized by the movement of children for a variety of purposes related to health, fertility, social responsibility, caregiving relationships, apprenticeship, and educational opportunities. Despite numerous characterizations of fostering as fundamentally reciprocal in nature (Bledsoe 1989), such practices are not always beneficial or voluntary. Several scholars have highlighted the role that poverty plays in the circulation of children, often transferring the productive contributions of children from one household to another (Goody 1982; Leinaweaver 2007; Schrauwers 1999). Thus, processes that shape social relationships are not always unambiguously positive, alliance-building strategies, but may also be necessitated by poverty, inequality, and disease. Child fostering has a long history in Lesotho as a regular strategy for sharing responsibility and supporting and connecting kin (Murray 1981; Page 1989). In Lesotho, HIV/AIDS has been a major factor in changing fostering patterns, as it has elsewhere in sub-Saharan Africa. 4 Household migration has been an important coping strategy employed by children and families impacted by AIDS (Ansell van Blerk 2004). Although orphans are still predominantly cared for within the family, researchers worry that family and communitybased networks of care are becoming saturated (Abebe Aase 2007; Courtney Iwaniec 2009; L. Townsend Dawes 2004). Others also note that increased pressure on caregivers has resulted in some children receiving inadequate care, as caregivers struggle to meet these children’s needs, whether financial (Ansell van Blerk 2004; Kidman, Petrow Heymann 2007) or emotional and psycho-social (Ansell Young 2004; Nyesigomwe 2005). The emergence and uncertainty of matrilocal care must be understood as embedded in a context4UNICEF (2010) estimates that there are 110,000?20,000 AIDS orphans in Lesotho; of these children, 12,000 are HIV-positive. J R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPagethat is constrained not only by AIDS and poverty but also by a varie.

Author ManuscriptBentov and ReedPageof age-related deficits in angiogenesis, which has an

Leupeptin (hemisulfate) site Author ManuscriptBentov and ReedPageof age-related deficits in angiogenesis, which has an adverse effect on the development of an effective microcirculation38. In an explant model, age-related deficiencies in angiogenesis were reversed, in part, by stimulation with angiogenic growth factors39. IIC. Extracellular matrix and tissue remodeling During the last phase of wound healing, the extracellular matrix begins to remodel and the wound undergoes further contraction. Fibroblasts assume a myofibroblast phenotype characterized by bundles of alpha smooth muscle actin-containing microfilaments. Synchronized collagen reorganization occurs by synthesis and catabolism (although at a much slower rate than in previous stages), which allows the granulation tissue to turn into a scar. Deposition and remodeling of collagen is slower in aged animals resulting in less scar formation40. Moreover, the collagen deposited has a looser, more disorganized matrix that has decreased tensile strength. The changes in aged collagen matrix reflect decreases in circulating factors, in particular reduced levels of TGF-1 – a potent stimulator of collagen synthesis 41. Of note, dermal fibroblasts from aged and young donors exposed to TGF-1 exhibit similar biosynthetic and contractile properties42. Other matrix components43 that are altered with age (Figure 3C) include: decreased osteonectin (also known as secreted protein acidic and rich in cysteine – SPARC), increases in thrombospondin44 and alterations in fibronectin and laminin45, 46. Non-protein components of the extracellular matrix get BIM-22493 include glycosaminoglycans, such as hyaluronan, which interact with other matrix components to maintain hydration in the dermis. Hyaluronan is a linear disaccharide polymer that can range from 2?5,000 disaccharides with molecular masses up to 2?04 kDa. Hyaluronan size determines its biologic properties: high molecular weight forms can inhibit proliferation and migration of many cell types, whereas middle and lower molecular weight forms usually promote tissue formation46. Hyaluronan content is maintained in aged wound dermis, but its degradation is reduced47. Wound healing also requires matrix metalloproteinases (MMPs), which promote cell proliferation and vessel ingrowth by degrading the existing extracellular matrix. MMP activity is balanced, in part, by endogenous tissue inhibitors of metalloproteinases. Aged tissues are associated with dysregulation of MMP activity48, with a tendency toward overexpression of MMPs49 and reduced levels of tissue inhibitors of metalloproteinases50. As highlighted above, alterations occur during each stage of wound repair in aging, and many of these changes negatively impact the microcirculation. Nonetheless, given sufficient time aged animals eventually (age related delay is roughly 30?0 ) catch up to their young counterparts with respect to most aspects of tissue repair51.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptIII. The Surgical Context of Wound Repair and AgingMeasures that support the microcirculation improve wound repair, thereby reducing the risk of postoperative dehiscence and infection52. General pre-operative measures such as smoking cessation and optimal management of co-morbid medical conditions have been reviewed in other contexts53, 54. For the purpose of this review, we will focus on interventions in the peri-operative setting. IIIA. Oxygen administration Wound healing is dependent upon adequate levels.Author ManuscriptBentov and ReedPageof age-related deficits in angiogenesis, which has an adverse effect on the development of an effective microcirculation38. In an explant model, age-related deficiencies in angiogenesis were reversed, in part, by stimulation with angiogenic growth factors39. IIC. Extracellular matrix and tissue remodeling During the last phase of wound healing, the extracellular matrix begins to remodel and the wound undergoes further contraction. Fibroblasts assume a myofibroblast phenotype characterized by bundles of alpha smooth muscle actin-containing microfilaments. Synchronized collagen reorganization occurs by synthesis and catabolism (although at a much slower rate than in previous stages), which allows the granulation tissue to turn into a scar. Deposition and remodeling of collagen is slower in aged animals resulting in less scar formation40. Moreover, the collagen deposited has a looser, more disorganized matrix that has decreased tensile strength. The changes in aged collagen matrix reflect decreases in circulating factors, in particular reduced levels of TGF-1 – a potent stimulator of collagen synthesis 41. Of note, dermal fibroblasts from aged and young donors exposed to TGF-1 exhibit similar biosynthetic and contractile properties42. Other matrix components43 that are altered with age (Figure 3C) include: decreased osteonectin (also known as secreted protein acidic and rich in cysteine – SPARC), increases in thrombospondin44 and alterations in fibronectin and laminin45, 46. Non-protein components of the extracellular matrix include glycosaminoglycans, such as hyaluronan, which interact with other matrix components to maintain hydration in the dermis. Hyaluronan is a linear disaccharide polymer that can range from 2?5,000 disaccharides with molecular masses up to 2?04 kDa. Hyaluronan size determines its biologic properties: high molecular weight forms can inhibit proliferation and migration of many cell types, whereas middle and lower molecular weight forms usually promote tissue formation46. Hyaluronan content is maintained in aged wound dermis, but its degradation is reduced47. Wound healing also requires matrix metalloproteinases (MMPs), which promote cell proliferation and vessel ingrowth by degrading the existing extracellular matrix. MMP activity is balanced, in part, by endogenous tissue inhibitors of metalloproteinases. Aged tissues are associated with dysregulation of MMP activity48, with a tendency toward overexpression of MMPs49 and reduced levels of tissue inhibitors of metalloproteinases50. As highlighted above, alterations occur during each stage of wound repair in aging, and many of these changes negatively impact the microcirculation. Nonetheless, given sufficient time aged animals eventually (age related delay is roughly 30?0 ) catch up to their young counterparts with respect to most aspects of tissue repair51.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptIII. The Surgical Context of Wound Repair and AgingMeasures that support the microcirculation improve wound repair, thereby reducing the risk of postoperative dehiscence and infection52. General pre-operative measures such as smoking cessation and optimal management of co-morbid medical conditions have been reviewed in other contexts53, 54. For the purpose of this review, we will focus on interventions in the peri-operative setting. IIIA. Oxygen administration Wound healing is dependent upon adequate levels.

Nsfer’ (CPET), that makes the mechanistic implication explicit.9 We support using

Nsfer’ (CPET), that makes the mechanistic implication explicit.9 We support using this term to refer to any chemical reaction where one H+ and one e- are transferred in a single kinetic step. CPET is equivalent to the `CEP’ term (MGCD516 web concerted electron/proton) used by Hammarstr and coworkers,10 and the `EPT’ moniker (electron/proton transfer) used by Meyer et al.1a CPET (/CEP/EPT) processes contrast with stepwise processes involving either initial ET followed by PT, or PT followed by ET, as shown in Scheme 1. In this and the other Schemes in this review, proton transfer processes are horizontal lines, ET processes are vertical lines, and processes that involve get ARA290 protons and electrons are diagonal lines. Readers should be aware that other workers have chosen other representations that better illustrate their particular concerns (cf., ref. 5). The stepwise pathways in Scheme 1 for 1H+/1e- transfer reactions are proton transfer followed by electron transfer (PT-ET) and ET-PT. Many examples of PT-ET, ET-PT, and concerted reactions are known. For instance, the groups of Ingold and Foti have shown that acidic phenols can react by a PT-ET type mechanism termed `sequential proton-loss electron transfer’ or SPLET (adding to the list of acronyms).11?213 Hammarstr et al. have shown that the aqueous ruthenium-tyrosine complexes can undergo ET-PT, CPET, or PT-ET processes depending on the pH.10,14 ET-PT pathways are particularly well documented in the electrochemical literature, where they are a type of EC mechanism (electrochemical then chemical).15 The factors that determine which path is followed are discussed in Section 6, below. 2.2 Hydrogen Atom Transfer (HAT) Hydrogen atom transfer has been studied by physical and organic chemists for over a century.16 It is key to the rate and selectivity of a variety of free radical reactions, including radical chains as in autoxidation and combustion. The abstraction of H?from organic compounds by peroxyl radicals has been especially widely discussed and researched because they are important to disease states, aging and food preservation.17 In the older physical-organic literature there was no need to define HAT, as it was selfevident that this referred to reactions involving concerted transfer of H?from a donor (XH) to an acceptor (Y, Scheme 2).18 We will use this definition here, noting that `concerted’ implies a single kinetic step for transfer of the two particles but does not necessarily imply synchronous transfer. By this definition, HAT is one class of CPET reactions.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptIn the last 25 years it has been recognized that transition metal coordination complexes and metalloenzymes can undergo HAT reactions, and that there is overlap between traditional HAT reactions and PCET. This has led to the appearance of a number of new definitions and new thinking about HAT.192021?2 For instance, computationally there is a clear orbital distinction between degenerate H?exchange between toluene and benzyl radical, versus exchange between phenol and phenoxyl radical.19 In toluene, the H+ and e- start in the same bond and end in the same bond. In the phenol/phenoxyl reaction, however, the proton is in the molecular plane but the transferring electron is in an orthogonal symmetry orbital. 19 To deal with such distinctions, Meyer et al. have proposed to restrict HAT to reactions where “the transferring electron and proton come from the same bond.”1,20 T.Nsfer’ (CPET), that makes the mechanistic implication explicit.9 We support using this term to refer to any chemical reaction where one H+ and one e- are transferred in a single kinetic step. CPET is equivalent to the `CEP’ term (concerted electron/proton) used by Hammarstr and coworkers,10 and the `EPT’ moniker (electron/proton transfer) used by Meyer et al.1a CPET (/CEP/EPT) processes contrast with stepwise processes involving either initial ET followed by PT, or PT followed by ET, as shown in Scheme 1. In this and the other Schemes in this review, proton transfer processes are horizontal lines, ET processes are vertical lines, and processes that involve protons and electrons are diagonal lines. Readers should be aware that other workers have chosen other representations that better illustrate their particular concerns (cf., ref. 5). The stepwise pathways in Scheme 1 for 1H+/1e- transfer reactions are proton transfer followed by electron transfer (PT-ET) and ET-PT. Many examples of PT-ET, ET-PT, and concerted reactions are known. For instance, the groups of Ingold and Foti have shown that acidic phenols can react by a PT-ET type mechanism termed `sequential proton-loss electron transfer’ or SPLET (adding to the list of acronyms).11?213 Hammarstr et al. have shown that the aqueous ruthenium-tyrosine complexes can undergo ET-PT, CPET, or PT-ET processes depending on the pH.10,14 ET-PT pathways are particularly well documented in the electrochemical literature, where they are a type of EC mechanism (electrochemical then chemical).15 The factors that determine which path is followed are discussed in Section 6, below. 2.2 Hydrogen Atom Transfer (HAT) Hydrogen atom transfer has been studied by physical and organic chemists for over a century.16 It is key to the rate and selectivity of a variety of free radical reactions, including radical chains as in autoxidation and combustion. The abstraction of H?from organic compounds by peroxyl radicals has been especially widely discussed and researched because they are important to disease states, aging and food preservation.17 In the older physical-organic literature there was no need to define HAT, as it was selfevident that this referred to reactions involving concerted transfer of H?from a donor (XH) to an acceptor (Y, Scheme 2).18 We will use this definition here, noting that `concerted’ implies a single kinetic step for transfer of the two particles but does not necessarily imply synchronous transfer. By this definition, HAT is one class of CPET reactions.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptIn the last 25 years it has been recognized that transition metal coordination complexes and metalloenzymes can undergo HAT reactions, and that there is overlap between traditional HAT reactions and PCET. This has led to the appearance of a number of new definitions and new thinking about HAT.192021?2 For instance, computationally there is a clear orbital distinction between degenerate H?exchange between toluene and benzyl radical, versus exchange between phenol and phenoxyl radical.19 In toluene, the H+ and e- start in the same bond and end in the same bond. In the phenol/phenoxyl reaction, however, the proton is in the molecular plane but the transferring electron is in an orthogonal symmetry orbital. 19 To deal with such distinctions, Meyer et al. have proposed to restrict HAT to reactions where “the transferring electron and proton come from the same bond.”1,20 T.

S: Tortricidae, Aesiocopa necrofolia. Distribution. Costa Rica, ACG. Etymology. We dedicate

S: Tortricidae, Aesiocopa necrofolia. Distribution. Costa Rica, ACG. Etymology. We dedicate this species to Ana Piedra in recognition of her diligent efforts for the ACG Programa de Educacion Biol ica. Comments. A. anapiedrae shares with the diatraeae and guadaluperodriguezae groups a somewhat CBR-5884 site depressed body (dorso-ventrally), short antenna, and relatively small body size; however, it has an inflexible (unfolded) hypopygium without any pleats, a very small smooth area on lateral face of scutellum (0.2 ?as high as maximum height of lateral face), and parasitizes a completely different group of Lepidoptera. The sculpture of propodeum and the areola shape are similar to species of the diatraeae group (but the latter group has a pleated hypopygium, a longer ovipositor, and the smooth area on lateral face of scutellum is at least 0.5 ?as high as maximum height of lateral face). A. anapiedrae does not resemble typical species of Apanteles because of its propodeal areola and unpleated hypopygium. It is likely to represent a derived speciesgroup within Apanteles, or it might be placed in another genus. Pending further study of worldwide genera of Microgastrinae, we decided to describe the species under Apanteles because is the closest match at the moment. Apanteles anariasae Fern dez-Triana, sp. n. http://zoobank.org/6ABE9F0E-2996-4580-8943-F7216EFF341F http://species-id.net/wiki/Apanteles_anariasae Fig. 71 Type locality. COSTA RICA, Guanacaste, ACG, Sector Santa Rosa, Bosque San Emilio, 300m, 10.84389, -85.61384. Holotype. in CNC. Specimen labels: 1. DHJPAR0013054. 2. 24 Apr. 2000, San Emilio Trap. Saroglitazar Magnesium site Description. Female. Body color: body mostly dark except for some sternites which may be pale. Antenna color: scape, pedicel, and flagellum dark. Coxae color (pro-, meso-, metacoxa): dark, dark, dark. Femora color (pro-, meso-, metafemur): anteriorly dark/ posteriorly pale, dark, dark. Tibiae color (pro-, meso-, metatibia): pale, pale, anteriorly pale/posteriorly dark. Tegula and humeral complex color: both dark. Pterostigma color: mostly pale and/or transparent, with thin dark borders. Fore wing veins color: partially pigmented (a few veins may be dark but most are pale). Antenna length/body length: antenna shorter than body (head to apex of metasoma), not extending beyond anterior 0.7 metasoma length. Body in lateral view: not distinctly flattened dorso entrally.Jose L. Fernandez-Triana et al. / ZooKeys 383: 1?65 (2014)Body length (head to apex of metasoma): 2.0 mm or less. Fore wing length: 2.0 mm or less. Ocular cellar line/posterior ocellus diameter: 2.0?.2. Interocellar distance/posterior ocellus diameter: 1.7?.9. Antennal flagellomerus 2 length/width: 2.6?.8. Antennal flagellomerus 14 length/width: 1.1?.3. Length of flagellomerus 2/length of flagellomerus 14: 2.0?.2. Tarsal claws: simple. Metafemur length/width: 2.8?.9. Metatibia inner spur length/metabasitarsus length: 0.4?.5. Anteromesoscutum: mostly with deep, dense punctures (separated by less than 2.0 ?its maximum diameter). Mesoscutellar disc: mostly smooth. Number of pits in scutoscutellar sulcus: 11 or 12. Maximum height of mesoscutellum lunules/maximum height of lateral face of mesoscutellum: 0.6?.7. Propodeum areola: completely defined by carinae, including transverse carina extending to spiracle. Propodeum background sculpture: partly sculptured, especially on anterior 0.5. Mediotergite 1 length/width at posterior margin: 1.1?.3. Mediotergite 1 shape: slightly widening from anteri.S: Tortricidae, Aesiocopa necrofolia. Distribution. Costa Rica, ACG. Etymology. We dedicate this species to Ana Piedra in recognition of her diligent efforts for the ACG Programa de Educacion Biol ica. Comments. A. anapiedrae shares with the diatraeae and guadaluperodriguezae groups a somewhat depressed body (dorso-ventrally), short antenna, and relatively small body size; however, it has an inflexible (unfolded) hypopygium without any pleats, a very small smooth area on lateral face of scutellum (0.2 ?as high as maximum height of lateral face), and parasitizes a completely different group of Lepidoptera. The sculpture of propodeum and the areola shape are similar to species of the diatraeae group (but the latter group has a pleated hypopygium, a longer ovipositor, and the smooth area on lateral face of scutellum is at least 0.5 ?as high as maximum height of lateral face). A. anapiedrae does not resemble typical species of Apanteles because of its propodeal areola and unpleated hypopygium. It is likely to represent a derived speciesgroup within Apanteles, or it might be placed in another genus. Pending further study of worldwide genera of Microgastrinae, we decided to describe the species under Apanteles because is the closest match at the moment. Apanteles anariasae Fern dez-Triana, sp. n. http://zoobank.org/6ABE9F0E-2996-4580-8943-F7216EFF341F http://species-id.net/wiki/Apanteles_anariasae Fig. 71 Type locality. COSTA RICA, Guanacaste, ACG, Sector Santa Rosa, Bosque San Emilio, 300m, 10.84389, -85.61384. Holotype. in CNC. Specimen labels: 1. DHJPAR0013054. 2. 24 Apr. 2000, San Emilio Trap. Description. Female. Body color: body mostly dark except for some sternites which may be pale. Antenna color: scape, pedicel, and flagellum dark. Coxae color (pro-, meso-, metacoxa): dark, dark, dark. Femora color (pro-, meso-, metafemur): anteriorly dark/ posteriorly pale, dark, dark. Tibiae color (pro-, meso-, metatibia): pale, pale, anteriorly pale/posteriorly dark. Tegula and humeral complex color: both dark. Pterostigma color: mostly pale and/or transparent, with thin dark borders. Fore wing veins color: partially pigmented (a few veins may be dark but most are pale). Antenna length/body length: antenna shorter than body (head to apex of metasoma), not extending beyond anterior 0.7 metasoma length. Body in lateral view: not distinctly flattened dorso entrally.Jose L. Fernandez-Triana et al. / ZooKeys 383: 1?65 (2014)Body length (head to apex of metasoma): 2.0 mm or less. Fore wing length: 2.0 mm or less. Ocular cellar line/posterior ocellus diameter: 2.0?.2. Interocellar distance/posterior ocellus diameter: 1.7?.9. Antennal flagellomerus 2 length/width: 2.6?.8. Antennal flagellomerus 14 length/width: 1.1?.3. Length of flagellomerus 2/length of flagellomerus 14: 2.0?.2. Tarsal claws: simple. Metafemur length/width: 2.8?.9. Metatibia inner spur length/metabasitarsus length: 0.4?.5. Anteromesoscutum: mostly with deep, dense punctures (separated by less than 2.0 ?its maximum diameter). Mesoscutellar disc: mostly smooth. Number of pits in scutoscutellar sulcus: 11 or 12. Maximum height of mesoscutellum lunules/maximum height of lateral face of mesoscutellum: 0.6?.7. Propodeum areola: completely defined by carinae, including transverse carina extending to spiracle. Propodeum background sculpture: partly sculptured, especially on anterior 0.5. Mediotergite 1 length/width at posterior margin: 1.1?.3. Mediotergite 1 shape: slightly widening from anteri.

Vo in a manner similar to that possible with cells obtained

Vo in a manner similar to that possible with cells obtained at term. The amount of tissue available is Doravirine supplier undoubtedly a limiting Avasimibe web factor in conducting such experiments. Unfortunately we know little about implantation in human and related primates and virtually nothing about the characteristic of the invasive STB that paves the way for placenta formation (2). In particular, it is not completely clear how this syncytium forms, although it is believed to have its origins through proliferation and fusion of a population of cytotrophoblast cells derived from polar trophectoderm overlaying and in immediate contact with the epiblast. However, can an epiblast origin for this syncytium be definitely ruled out given the paucity of histological data? Such a beginning would reconcile the controversies that have raged about whether or not human pluripotent stem cells of the epiblast type can differentiate into trophoblast (40?2), a concept not readily accepted by some embryologists, but supported by an imposing array of experimental data (13?9, 31?3, 43?8), including the results presented in this paper where we have confirmed the STB nature of the >70-m fraction but also demonstrated many features in gene expression in common with epiblast stem cells (Fig. 4).1. Gude NM, Roberts CT, Kalionis B, King RG (2004) Growth and function of the normal human placenta. Thromb Res 114(5?):397?07. 2. James JL, Carter AM, Chamley LW (2012) Human placentation from nidation to 5 weeks of gestation. Part I: What do we know about formative placental development following implantation? Placenta 33(5):327?34. 3. Huppertz B (2008) The anatomy of the normal placenta. J Clin Pathol 61(12): 1296?302. 4. Boyd JD, Hamilton WJ (1970) The Human Placenta (Heffer Sons, Cambridge). 5. Hertig AT, Rock J, Adams EC (1956) A description of 34 human ova within the first 17 days of development. Am J Anat 98(3):435?93. 6. Huppertz B (2007) The feto-maternal interface: Setting the stage for potential immune interactions. Semin Immunopathol 29(2):83?4.Materials and MethodsHuman ESC Culture and Differentiation. Human ESC (H1; WA01) originated from WiCell Research Institute and were cultured in six-well tissue culture plates (Thermo Scientific) on Matrigel (BD Bioscience)-coated plates. For maintenance, these cells were cultured in mTeSR1 medium (Stemcell Technologies). The culture medium was changed daily, and cells were passaged every 5? d by using Gentle Cell Dissociation Reagent (Stemcell Technologies). They were cultured under an atmosphere of 95 (vol/vol) air and 5 (vol/vol) CO2 at 37 . For trophoblast differentiation, a procedure described in Amita et al. (14) was used. Briefly, the day after passaging onto Matrigelcoated dishes at 1.2 ?104 cells/cm2, the culture medium was changed to DME/F12 medium (Thermo Scientific) with knock-out serum replacement (KOSR, Invitrogen) that had been conditioned by MEFs and supplemented with FGF2 (4 ng/mL). After 24 h, the conditioned medium was replaced with daily changes of DME/F12/KOSR medium lacking MEF conditioning and minus FGF2, but containing BMP4 (10 ng/mL), A83-01 (1 M), and PD173074 (0.1 M) (BAP treatment) for up to 8 d (14). Control cultures were maintained in conditioned medium containing 4 ng/mL FGF2. Cell Separation on Strainers. Cell sorting by relative cell diameter was conducted after completely dissociating the colonies. Complete cell dissociations could be achieved either after 14 min in 0.25 Trypsin-EDTA (Life Technologies) or.Vo in a manner similar to that possible with cells obtained at term. The amount of tissue available is undoubtedly a limiting factor in conducting such experiments. Unfortunately we know little about implantation in human and related primates and virtually nothing about the characteristic of the invasive STB that paves the way for placenta formation (2). In particular, it is not completely clear how this syncytium forms, although it is believed to have its origins through proliferation and fusion of a population of cytotrophoblast cells derived from polar trophectoderm overlaying and in immediate contact with the epiblast. However, can an epiblast origin for this syncytium be definitely ruled out given the paucity of histological data? Such a beginning would reconcile the controversies that have raged about whether or not human pluripotent stem cells of the epiblast type can differentiate into trophoblast (40?2), a concept not readily accepted by some embryologists, but supported by an imposing array of experimental data (13?9, 31?3, 43?8), including the results presented in this paper where we have confirmed the STB nature of the >70-m fraction but also demonstrated many features in gene expression in common with epiblast stem cells (Fig. 4).1. Gude NM, Roberts CT, Kalionis B, King RG (2004) Growth and function of the normal human placenta. Thromb Res 114(5?):397?07. 2. James JL, Carter AM, Chamley LW (2012) Human placentation from nidation to 5 weeks of gestation. Part I: What do we know about formative placental development following implantation? Placenta 33(5):327?34. 3. Huppertz B (2008) The anatomy of the normal placenta. J Clin Pathol 61(12): 1296?302. 4. Boyd JD, Hamilton WJ (1970) The Human Placenta (Heffer Sons, Cambridge). 5. Hertig AT, Rock J, Adams EC (1956) A description of 34 human ova within the first 17 days of development. Am J Anat 98(3):435?93. 6. Huppertz B (2007) The feto-maternal interface: Setting the stage for potential immune interactions. Semin Immunopathol 29(2):83?4.Materials and MethodsHuman ESC Culture and Differentiation. Human ESC (H1; WA01) originated from WiCell Research Institute and were cultured in six-well tissue culture plates (Thermo Scientific) on Matrigel (BD Bioscience)-coated plates. For maintenance, these cells were cultured in mTeSR1 medium (Stemcell Technologies). The culture medium was changed daily, and cells were passaged every 5? d by using Gentle Cell Dissociation Reagent (Stemcell Technologies). They were cultured under an atmosphere of 95 (vol/vol) air and 5 (vol/vol) CO2 at 37 . For trophoblast differentiation, a procedure described in Amita et al. (14) was used. Briefly, the day after passaging onto Matrigelcoated dishes at 1.2 ?104 cells/cm2, the culture medium was changed to DME/F12 medium (Thermo Scientific) with knock-out serum replacement (KOSR, Invitrogen) that had been conditioned by MEFs and supplemented with FGF2 (4 ng/mL). After 24 h, the conditioned medium was replaced with daily changes of DME/F12/KOSR medium lacking MEF conditioning and minus FGF2, but containing BMP4 (10 ng/mL), A83-01 (1 M), and PD173074 (0.1 M) (BAP treatment) for up to 8 d (14). Control cultures were maintained in conditioned medium containing 4 ng/mL FGF2. Cell Separation on Strainers. Cell sorting by relative cell diameter was conducted after completely dissociating the colonies. Complete cell dissociations could be achieved either after 14 min in 0.25 Trypsin-EDTA (Life Technologies) or.