text:
759610 Susy Gabriele Storti gabriele.stortimd@gmail.com 2021-11-18 11:57:12 2021-11-18 11:57:12
212662 evaldofavi@gmail.com Evaldo Favi No 2021-10-19 08:28:53 2021-11-18 11:57:12
212663 francesca.alba.96@gmail.com No 2021-10-19 08:28:53 2021-10-19 08:28:53
212664 bong-sung.kim@usz.ch No 2021-10-19 08:28:53 2021-10-19 08:28:53
212665 valeriocervelli@virgilio.it No 2021-10-19 08:28:53 2021-10-19 08:28:53
74121 gabriele.stortimd@gmail.com Gabriele Storti 1 2021-10-19 08:28:53 2021-11-18 11:57:12
79541 lindsay.dong@mdpi.com Lindsay Dong 2 2021-11-22 04:23:15 2021-11-22 04:23:16
Adipose-Derived Stem/Stromal Cells in Kidney Transplantation
Subjects: Transplantation | Surgery
Gabriele Storti
Kidney transplantation (KT) is the gold standard treatment of end-stage renal disease. Among the many peri-operative complications that can jeopardize transplant outcomes, ischemia–reperfusion injury (IRI) deserves special consideration as it is associated with delayed graft function, acute rejection, and premature transplant loss. Adipose stem/stromal cells (ASCs) possess specific characteristics that could help prevent, reduce, or reverse IRI.
Kidney transplantation (KT) is the gold standard treatment of end-stage renal disease (ESRD). In the last two decades, the overwhelming discrepancy between available organs and patients in the transplant waiting list has led to a progressive expansion of the criteria adopted for donors' acceptance and allocation. As such, an increasing number of so-called marginal kidneys are now being transplanted into high-risk recipients. The main consequence of this aggressive policy is a striking rise in the incidence of delayed graft function (DGF) [1][2][3]. Clinically defined as the need for dialysis during the first post-transplant week, DGF is a complex entity that can negatively affect both patient and allograft survival [4]. The most relevant risk factors for DGF are expanded criteria (ECD) or donation after circulatory death (DCD) donors, prolonged warm (WIT) or cold ischemia time (CIT), and recipient sensitization [5]. Among the various peri-transplant events contributing to the development of DGF, ischemia–reperfusion injury (IRI) deserves special consideration as it is inevitable and represents the major determinant of acute tubular necrosis (ATN), the leading histological finding associated with DGF [2]. IRI is accompanied by a massive pro-inflammatory response and can trigger multiple cell death programs, endothelial dysfunction, transcriptional reprogramming, and activation of both innate and adaptive immunity [6]. Considering the strong association between IRI, DGF, acute rejection (AR), and progressive interstitial fibrosis with tubular atrophy (IF/TA) as well as their detrimental impact on allograft function and survival, the prevention and treatment of IRI have been recognized as primary issues for the transplant community [7].
2. Mechanisms of Action
In order to explain the positive effects of ASCs on renal injury, two mechanisms of action have been proposed: differentiative and paracrine. In 2010, Li et al. demonstrated that, in a murine model of acute kidney injury (AKI), human ASCs (hASCs) injected in the tail vein 24 h after the induction of IRI could trans-differentiate into RTECs and repair the damage associated with ATN. At six months of follow-up, the animals treated with hASCs showed normal renal histology whilst the control group exhibited fibrosis and glomerular sclerosis [8]. ASCs' ability to trans-differentiate into RTECs was confirmed by other studies in which mouse or rabbit kidney scaffolds were seeded with ASCs through the renal artery or ureter [9]. During these experiments, it was observed that ASCs were able to engraft the glomerular, tubular, and vascular areas of the scaffold, eventually trans-differentiating into RTECs and endothelial cells. The authors postulated that the attachment to the scaffold was mediated by the stromal cell-derived factor 1α (SDF-1α
) [10]. It remains unclear whether ASCs could trans-differentiate into other renal cell types or build up a proper tridimensional structure. ASCs also exert complex paracrine actions [11]. The main soluble molecules produced in response to IRI and mediating ASCs' pro-angiogenic, proliferative, and anti-apoptotic effects are IGF-1, SDF-1α, and VEGF [12][13]. HGF, IL-10, TGF-β1, and NO have been recognized as anti-inflammatory and anti-fibrosis agents [14] whereas tumor necrosis factor-inducible gene 6 protein (TSG-6) [15] and indoleamine 2,3-dioxygenase (IDO) [16][17] seem to promote the development of regulatory T-cells (Tregs) and induce tolerance via up-regulation of the FOX-P3 pathway [18].
EVs represent further mediators of ASCs' function [19]. Classified as exosomes (30–100 nm) or micro-vesicles (100–1000 nm) depending on their maximal diameter, EVs can change their content and secretion pattern in response to different external stimulations [20][21]. Hypoxia, extra-cellular calcium variations, and thermal stress are powerful triggers of EVs secretion [22][23]. It has been hypothesized that ASC-induced renal tissue repair is mediated by specific mRNAs and miRNAs contained in the EVs [24]. In particular, miR-24, miR-29, and several members of the let-7 miRNA family might be involved in the regenerative, proliferative, anti-apoptotic, and anti-inflammatory response to IRI [25] whereas the immunomodulating effects on dendritic cells could be mediated by miR-21-5p, miR-142-3p, miR-223-3p, and miR-126-3p [26]. EV-related mRNAs can contribute to cell differentiation (RAX2, EPX, SCNN1G), immunomodulation (IL1RN, MT1X, CRLF1), ECM remodeling (COL4A2, IBSP), cell-cycle progress (SENP2, RBL1, CDC14B), angiogenesis, and fibrosis (TGF-β1, TGF-β3, FURIN, ENG) [27]. Investigating the role of EVs in AKI, Gao et al. observed that ASC-derived exosomes could significantly decrease the expression of important inflammatory mediators, such as NF-κB, p65 protein, and TNF-α [28]. Exosomes can also up-regulate SIRT-1, thus protecting RTECs from oxidative stress [29]. There is evidence that ASCs' EVs are involved in cell survival regulation and tissue repair. As a matter of fact, exosomes release is associated with increased expression of the pro-survival protein BCL2 and decreased expression of the pro-apoptotic caspase-3, caspase-9, and BAX [28]. Exosomes also favor angiogenesis induction through up-regulation of HIF-1α and VEGF [28]. According to a recent meta-analysis of pre-clinical rodent models of AKI, ASC-derived EVs administration improves renal function, reducing apoptosis and inflammation [30]. Remarkably, some reports suggest that EV-induced renal protection from IRI exhibits a concentration-dependent effect [31].
Main ASCs and ASC-derived EVs mechanism of actions in IRI and KT models are summarized in Figure 1 and Figure 2.
Figure 1. Adipose-derived stem/stromal cells (ASCs) mechanisms of action in kidney transplant ischemia–reperfusion injury and tolerance induction models (↑, increased; ↓, decreased; RTEC, renal tubular epithelial cell; SDF-1, stromal cell-derived factor 1; IL-10, interleukin 10; TGF-1, transforming growth factor 1; NO, nitric oxide; TSG-6, tumor necrosis factor-inducible gene 6; IDO, indoleamine 2,3-dioxygenase; VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor; HGF, hepatocyte growth factor; IGF-1, insulin-like growth factor).
Figure 2. Adipose-derived stem/stromal cell extra-cellular vesicles (EVs) mechanisms of action in kidney transplant ischemia–reperfusion injury and tolerance-induction models (↑, increased; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; p65 protein, REL-associated protein; TNF, tumor necrosis factor; SIRT-1, sirtuin-1; RAX2, retina and anterior neural fold homeobox protein 2; EPX, eosinophil peroxidase; SCNN1G, sodium channel epithelial 1 subunit gamma; BCL2, B-cell lymphoma 2; BAX, bcl2-like protein 4; COL4A2, collagen type IV alpha 2 chain; IBSP, integrin binding sialoprotein; TGF-1, transforming growth factor 1; TGF-3, transforming growth factor 3; ENG, endoglin; HIF-1, hypoxia-inducible factor-1; VEGF, vascular endothelial growth factor; SENP2, SUMO specific peptidase 2; RBL1, retinoblastoma-like protein 1; CDC14B, dual specificity protein phosphatase CDC14B; miR, micro RNA; IL1RN, interleukin 1 receptor antagonist; MT1X, metallothionein 1X; CRLF1, cytokine receptor like factor 1).
3. Harvesting Procedures
ASCs reside in peri-vascular niches within the adipose tissue, constituting about 20% of the cellular population of the SVF. Two main ASCs harvesting techniques are currently available: lipoaspirate and adipose tissue biopsy. Following specimen collection, the ECM of the adipose tissue undergoes enzymatic or mechanical disruption. The SVF released during the procedure is seeded and expanded in vitro to obtain ASCs [32]. Cultivation and expansion allow to produce a large number of ASCs from a relatively small sample of adipose tissue and permit to collect purified cellular products [33]. However, these methods are expensive, time-consuming, and require specific Good Manufacturing Practice (GMP) facilities. Therefore, it is unlikely that they can be used in the peri-operative setting of a deceased donor KT [34]. Allogenic non-donor derived ASCs represent an intriguing option as off-the-shelf cellular products. Nonetheless, some authors remain concerned that prolonged culture may cause cellular senescence and favor the acquisition of a pro-inflammatory phenotype [35].
The process required for SVF extraction is easy and expeditious enough that it can be performed in a timely manner in most hospitals. The SVF is a composite cellular mixture with wide intra- and inter-individual variability in cells quality and quantity, depending on patient' characteristics, harvesting procedure, extraction technique, and isolation method [36]. Such heterogeneity represents a remarkable issue as it negatively affects standardization and reproducibility of the vast majority of research protocols involving the SVF. Furthermore, the amount of adipose tissue required to obtain an adequate number of ASCs is significantly greater using the SVF extraction method than the ASCs expansion technique. Lastly, it is worth considering that the effects exerted on the transplanted kidney by the other cell types retrieved during the procedure (namely, pericytes, preadipocytes, endothelial cells, and fibroblasts) are still unclear [34]. Immunomodulatory, anti-inflammatory, and pro-tolerogenic properties have been postulated for the non-staminal cells of the SVF such as adipose resident M2 macrophages, Tregs, and regulatory invariant natural killer (NK) cells, but they have not been confirmed. [37][38][39].
The use of stem cell-based therapies in solid organ transplantation raises the question of whether autologous or allogenic cells should be preferred. Due to the lack of HLA class II molecules and the low expression of HLA class I and co-stimulatory signal molecules, ASCs are considered as immune-privileged cells [40]. However, the actual risk of allograft rejection associated with the use of allogenic ASCs remains obscure [41][42][43]. It has been demonstrated that donor-derived ASCs can promote the development of Tregs in vitro [18]. A certain degree of tolerance induction has also been also observed in vivo [44]. Nevertheless, a study comparing the efficacy of autologous or allogenic ASCs in a rat model of KT with total MHC mismatch, showed that donor-derived ASCs administration did not improve allograft survival and was associated with increased mortality through an immunologically-mediated mechanism [45]. Considering the paucity of data, it sounds reasonable to assume that autologous ASCs represent a safer option compared to allogenic ASCs. Some authors argue that, due to the toxic effects of uremia, ASCs harvested from ESRD patients have lower regenerative potential than those retrieved from healthy subjects; thus limiting the use of autologous ASC-based therapies in KT setting. However, there is evidence that the beneficial properties of ASCs are not affected by uremia or dialysis. In fact, Roemeling-van Rhijn and colleagues demonstrated that ASCs harvested from patients with CKD exhibited normal characteristics and function. Remarkably, ASCs' proliferative capacity and genetic stability remained consistent over time, also after repeated expansion and prolonged exposure to uremic serum. Furthermore, no differences could be detected between patients with normal or impaired renal function in ASCs' response to immune activation and ASCs' inhibitory effect on the proliferation of alloantigen-activated peripheral blood mononuclear cells [46].
In theory, the use of ASC-derived EVs could help address many issues associated with traditional cell-based therapies such as the need for time-consuming and technically demanding preparation processes and the risk of HLA sensitization. A recent meta-analysis of EV-based therapies in pre-clinical rodent models of AKI concluded that MSC-derived EVs administration was able to improve renal function, modulate the inflammatory response [47], and reduce cell apoptosis [30]. Overall, available studies suggest that EVs could be beneficial for the prevention and treatment of renal IRI [48][49]. On the contrary, current literature does not seem to support the utilization of EV-based therapies for KT rejection [45]. The highly variable composition of different EVs mixtures should also be considered as a potential limitation [22].
4. Timing, Dose, and Route of Administration
The proper definition of the optimal timing, dose, and route of administration represents a key factor for the implementation of ASC-based therapies in KT. Possible routes of administration that can maximize ASCs homing and survival in the allograft include intra-venous, intra-arterial, and intra-parenchymal. Continuous infusion using a kidney perfusion machine has also been proposed. There is evidence that MSCs and ASCs homing to the wounded areas of the kidney is promoted by a specific chemoattractant. Among the pathways involved in MSCs migration during IRI, the SDF-1/CXCR4 axis plays a major role. Over-expression of the CXCR4 gene enhances MSCs migration and promotes neo-angiogenesis and vascular repair [50][51][52]. These signals also regulate ASCs homing from the injection site to the transplanted organ [53].
The easiest route of administration of ASCs is intra-venous injection. However, when injected into the venous circulation, ASCs undergo a first pass effect in "filter organs" such as the liver, spleen, or lung. This phenomenon reduces the number of cells reaching the target site and can cause engulfment of the pulmonary micro-circulation, eventually leading to pulmonary embolism and death [54]. The results of clinical trials evaluating efficacy and safety of intravenously administered ASCs for the treatment of graft-versus-host disease demonstrate that the risk of micro-thrombosis and micro-embolism depends on the total number of cells infused. According to these studies, doses ranging from 0.4 to 9 × 106 MSCs or ASCs per kilogram represent a safe option [54][55][56].
Intra-arterial administration can also be considered. In theory, ASCs injection into the renal artery could increase the number of cells engrafting the kidney. A meta-analysis of MSC-based therapies in small animal models of AKI concluded that the intra-arterial route was associated with better renal function preservation (as assessed by serum creatinine concentration, SCr) than the intra-venous route [57]. It seems that, following injection into the renal artery, ASCs remain on site through passive mechanisms, mostly disappearing within 14 days [58]. Sporadic episodes of mesangioproliferative glomerulonephritis with aberrant adipocytic differentiation have been reported [59]. It can also be argued that, compared to intra-venous injection, intra-arterial administration is more invasive, entailing a greater risk of complications. Nevertheless, it should be recognized that a KT procedure offers wide kidney exposure and easy access to the renal artery.
ASCs intra-parenchymal injection represents another feasible option and it proved effective in several animal models of AKI [12]. This route of administration allows to combine ASCs with special biomaterials so as to extend their permanence and survival in the target site. An elegant study by Gao et al. showed that the use of thermosensitive chitosan chloride hydrogel (CCH) could improve the efficacy of ASC-based therapy in IRI. More in details, CCH was able to increase intra-renal ASCs retention and survival as well as to promote host kidney cells proliferation and resistance to apoptosis. At four weeks, the groups treated with CCH exhibited higher renal micro-vessels density and RTECs proliferation rates than controls, with better renal function. A possible explanation is that CCH favors a more suitable micro-environment for ASCs survival through enhanced ROS scavenging [60]. Encouraging results were also obtained by Zhou and colleagues using renal ECM hydrogel as an injectable scaffold to deliver ASCs into ischemic kidneys. In their experience, ECM hydrogel reduced ASCs dispersion and increased the number of viable ASCs retained in the target site. Furthermore, the authors observed that ECM hydrogel could inhibit ASCs apoptosis in vitro and promote ASCs proliferation, trans-differentiation into RTECs, and secretion [61]. Overall, available data suggest that ASCs cultivation in three-dimensional aggregates or spheroids combined with direct injection into the renal cortex can increase ASCs retention in the kidney and improve the efficacy of ASC-based therapies. Compared to bi-dimensional monolayers, three-dimensional configurations provide better resistance to oxidative stress and ischemia. They also facilitate cell migration and secretion [62][63].
ASCs can be delivered to the renal allograft using specific perfusion machines [64]. Several randomized clinical trials and meta-analysis have demonstrated that HMP reduces the incidence of DGF compared to SCS, particularly in case of ECD or DCD transplants [65]. Therefore, combining the benefits of continuous or pulsatile kidney perfusion with the regenerative potential of ASCs-based therapy represents a promising strategy. Preliminary data obtained from animal models of KT or acute kidney IRI showed that adding ASCs, BM-MSCs, or BM-MSC-derived EVs to the machine perfusion solution could improve renal function and allograft survival [66][67][68]. Current experience with NMP is more limited. Indeed, higher costs and logistic difficulties prevent widespread utilization of this preservation modality. Pool and coworkers investigated the effects of NMP plus hASCs in a model of porcine DCD KT. The experimental treatment was administered following kidney preservation with SCS [69] or HMP [13]. Interestingly, positive results were observed only in the HMP group. Compared to SCS, HMP ensured better ASCs homing and viability as well as higher resistance to oxidative stress and improved tubular regeneration capacity.
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Ullah, M.; Liu, D.D.; Rai, S.; Razavi, M.; Choi, J.; Wang, J.; Concepcion, W.; Thakor, A.S. A Novel Approach to Deliver Therapeutic Extracellular Vesicles Directly into the Mouse Kidney via Its Arterial Blood Supply. Cells 2020, 9, 937.
Wu, Q.; Ji, F.-K.; Wang, J.-H.; Nan, H.; Liu, D.-L. Stromal cell-derived factor 1 promoted migration of adipose-derived stem cells to the wounded area in traumatic rats. Biochem. Biophys. Res. Commun. 2015, 467, 140–145.
Liu, H.; Liu, S.; Li, Y.; Wang, X.; Xue, W.; Ge, G.; Luo, X. The role of SDF-1-CXCR4/CXCR7 axis in the therapeutic effects of hypoxia-preconditioned mesenchymal stem cells for renal ischemia/reperfusion injury. PLoS ONE 2012, 7, e34608.
Chen, Y.-T.T.; Yang, C.-C.C.; Zhen, Y.-Y.Y.; Wallace, C.G.; Yang, J.-L.L.; Sun, C.-K.K.; Tsai, T.-H.H.; Sheu, J.-J.J.; Chua, S.; Chang, C.-L.; et al. Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia–reperfusion injury. Stem Cell Res. Ther. 2013, 4, 62.
Furuichi, K.; Shintani, H.; Sakai, Y.; Ochiya, T.; Matsushima, K.; Kaneko, S.; Wada, T. Effects of adipose-derived mesenchymal cells on ischemia-reperfusion injury in kidney. Clin. Exp. Nephrol. 2012, 16, 679–689.
Shih, Y.C.; Lee, P.Y.; Cheng, H.; Tsai, C.H.; Ma, H.; Tarng, D.C. Adipose-derived stem cells exhibit antioxidative and antiapoptotic properties to rescue ischemic acute kidney injury in rats. Plast. Reconstr. Surg. 2013, 132, 940–951.
Fang, B.; Song, Y.P.; Liao, L.M.; Han, Q.; Zhao, R.C. Treatment of severe therapy-resistant acute graft-versus-host disease with human adipose tissue-derived mesenchymal stem cells. Bone Marrow Transplant. 2006, 38, 389–390.
Le Blanc, K.; Frassoni, F.; Ball, L.; Locatelli, F.; Roelofs, H.; Lewis, I.; Lanino, E.; Sundberg, B.; Bernardo, M.E.; Remberger, M.; et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: A phase II study. Lancet 2008, 371, 1579–1586.
Wang, Y.; He, J.; Pei, X.; Zhao, W. Systematic review and meta-Analysis of mesenchymal stem/stromal cells therapy for impaired renal function in small animal models. Nephrology 2013, 18, 201–208.
Sierra-Parraga, J.M.; Munk, A.; Andersen, C.; Lohmann, S.; Moers, C.; Baan, C.C.; Ploeg, R.J.; Pool, M.; Keller, A.K.; Møller, B.K.; et al. Mesenchymal stromal cells are retained in the porcine renal cortex independently of their metabolic state after renal intra-arterial infusion. Stem Cells Dev. 2019, 28, 1224–1235.
Kunter, U.; Rong, S.; Boor, P.; Eitner, F.; Müller-Newen, G.; Djuric, Z.; van Roeyen, C.R.; Konieczny, A.; Ostendorf, T.; Villa, L.; et al. Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes. J. Am. Soc. Nephrol. 2007, 18, 1754–1764.
Gao, J.; Liu, R.; Wu, J.; Liu, Z.; Li, J.; Zhou, J.; Hao, T.; Wang, Y.; Du, Z.; Duan, C.; et al. The use of chitosan based hydrogel for enhancing the therapeutic benefits of adipose-derived MSCs for acute kidney injury. Biomaterials 2012, 33, 3673–3681.
Zhou, C.; Zhou, L.; Liu, J.; Xu, L.; Xu, Z.; Chen, Z.; Ge, Y.; Zhao, F.; Wu, R.; Wang, X.; et al. Kidney extracellular matrix hydrogel enhances therapeutic potential of adipose-derived mesenchymal stem cells for renal ischemia reperfusion injury. Acta Biomater. 2020, 115, 250–263.
Zhao, X.; Qiu, X.; Zhang, Y.; Zhang, S.; Gu, X.; Guo, H. Three-Dimensional Aggregates Enhance the Therapeutic Effects of Adipose Mesenchymal Stem Cells for Ischemia-Reperfusion Induced Kidney Injury in Rats. Stem Cells Int. 2016, 2016.
Xu, Y.; Shi, T.; Xu, A.; Zhang, L. 3D spheroid culture enhances survival and therapeutic capacities of MSCs injected into ischemic kidney. J. Cell. Mol. Med. 2016, 20, 1203–1213.
Ferraresso, M.; Favi, E. Hypothermic Machine Perfusion in Kidney Transplantation: Back to the Future? J. Transplant. Technol. Res. 2015, 6.
Moers, C.; Smits, J.M.; Maathuis, M.-H.J.; Treckmann, J.; van Gelder, F.; Napieralski, B.P.; van Kasterop-Kutz, M.; van der Heide, J.J.H.; Squifflet, J.-P.; van Heurn, E.; et al. Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation. N. Engl. J. Med. 2009, 360, 7–19.
Iwai, S.; Sakonju, I.; Okano, S.; Teratani, T.; Kasahara, N.; Yokote, S.; Yokoo, T.; Kobayash, E. Impact of ex vivo administration of mesenchymal stem cells on the function of kidney grafts from cardiac death donors in rat. Transplant. Proc. 2014, 46, 1578–1584.
Wang, Y.L.; Li, G.; Zou, X.F.; Chen, X.B.; Liu, T.; Shen, Z.Y. Effect of autologous adipose-derived stem cells in renal cold ischemia and reperfusion injury. Transplant. Proc. 2013, 45, 3198–3202.
Gregorini, M.; Corradetti, V.; Pattonieri, E.F.; Rocca, C.; Milanesi, S.; Peloso, A.; Canevari, S.; De Cecco, L.; Dugo, M.; Avanzini, M.A.; et al. Perfusion of isolated rat kidney with Mesenchymal Stromal Cells/Extracellular Vesicles prevents ischaemic injury. J. Cell. Mol. Med. 2017, 21, 3381–3393.
Pool, M.; Eertman, T.; Parraga, J.S.; 't Hart, N.; van Rhijn, M.R.; Eijken, M.; Jespersen, B.; Reinders, M.; Hoogduijn, M.; Ploeg, R.; et al. Infusing mesenchymal stromal cells into porcine kidneys during normothermic machine perfusion: Intact MSCs can be traced and localised to Glomeruli. Int. J. Mol. Sci. 2019, 20, 3607.
adipose stem cells extra-cellular vesicles kidney transplantation ischemia–reperfusion injury tolerance rejection acute kidney injury regenerative medicine


"If you want a simple, straightforward indoor home security camera with top-of-the-line DIY specs and free cloud storage, Netgear's new Arlo Q is a safe bet"
"Wire-free cameras make Arlo the most flexible surveillance kit around, but beware of battery life and camera range issues."
"We were impressed with the video quality and wireless freedom Arlo provides, which are a major selling point over traditional wired IP cameras. Netgear has been forced to make a few sacrifices to prioritise battery life, meaning no sound or 1080p recording, and the system is expensive…"


Kicking it old school in everything from business philosophy to products that make digital photos look like film, VSCO's founders Joel Flory and Greg Lutze insist that they are building a company for keeps.
Greg Lutze and Joel Flory didn't set out to create an app. Despite the embarrassment of riches generated by a passel of solitary programmers, the founders of VSCO had no intention of dipping into a get-rich-quick scheme. They were doing quite nicely nurturing a little startup peddling digital editing tools to the likes of professional photographers and graphic designers, thank you.
Launching VSCO Cam–and version 2.0 this June–changed everything. The free iOS app offers a selection of presets (i.e., photo filters) and simple editing tools all rolled neatly into a mini social platform. Users can keep their photo "grids" within the app or share their favorites on Instagram, Facebook, Twitter, and Weibo.
With over a million downloads in the first week, the app's drawn a massive following that goes way beyond professional photographers. Thanks to a hashtag (#vscocam is added automatically when photos are taken or manipulated in its app), amateur photographers are also uploading their postage stamp-sized oeuvres at an astounding rate. Instagram alone boasts over 4 million VSCO-tagged images.
That VSCO (which stands for Visual Supply Company and is pronounced VisCo) even became a success in terms of generating revenue and staying cash flow positive comes as a bit of a surprise to both Lutze and Flory. But they both believe the social component is driving their business to new heights.
The two met years ago when Flory stumbled across Lutze's design work on a website for Flory's favorite band, Jimmy Eat World. He approached Lutze to do the branding for his father's construction business, then came back for his own wedding and portrait photography business. The pair eventually decided to pool their talents and start a side business offering WordPress site templates for photographers in March of 2011.
Site templates quickly gave way to thinking about building an entire platform. Around this time, Lutze brought on Zach Hodges, "our mad scientist," who helped them brainstorm better ways to generate revenue. Says Flory: "We went to creating tools that we would actually use as photographers and that's where VSCO was born." Their first products were film emulation tools for Adobe Lightroom and Adobe Camera Raw. "From there it just took off," he says, adding that they've been cash flow positive ever since.
With that success came an inevitable question: how to scale? "Instead of buying ads, we decided to create a tool to connect our community," Lutze says. That tool became the first iteration of the VSCO Cam app, which quietly debuted in the App Store in 2012 for $.99 a download. With Version 2.0, VSCO is dipping into a freemium model, but the two say that having a diversified business offering professional tool packs that cost about $120 keeps things running.
"A lot of times people say, 'you do such a good job marketing,'" says Lutze, "That's not an accurate statement." He maintains that coming from creative backgrounds, he and Flory can tell their customers "love the process of creating." It's up to VSCO then to cater to that.
Photographer Matt Furman goes Inside Jenna Lyons' Office for May's J.Crew Cover Story. Photos were edited with VSCO tools.
Flory points to VSCO's online "journal," which he says has always been an integral part of their offering. It's a stunning, visual blog that's been carefully curated by the VSCO team to showcase how a variety of photographers from all over the world use their tools. New York-based Matt Furman, who just happened to shoot Fast Company's May cover feature on J. Crew, was featured recently.
Is the community clamoring for VSCO to topple Instagram? "We never had any intention of building VSCO to be bought," says Flory, no doubt referring to the billion-dollar gambit Facebook took on Instagram. Instead, he says, they set up the business to be sustainable, and that means continuing to offer more than just an app–even though that can be lucrative. Apple's shelled out more than $10 billion in royalties to developers in the last five years.
Not that you'll find either one of them flying into an artistic rage if a preset isn't used by a customer the way they'd envisioned it. To this reporter's jaundiced eye, Lutze and Flory aren't too precious about the results. Rather, like others pushing the maker movement forward (Hi, Brit Morin!) they both seem to genuinely delight in seeing the results of others' creations with VSCO Cam.
"We really do love film," says Flory, "We geek out on a lot of the qualities of it and I wish everyone had the ability to shoot film." Since they can't, VSCO Cam comes close to imbuing a mobile photo (even those weirdly proportioned shoe selfies) with that timeless quality.


When I dial the exit number; 00 do I need to pause a couple seconds to allow it time to register? The same with the other numbers, i.e. the carrier number and then the 1 to enter the USA. Should I dial with pauses after any of these numbers or is it okay to just dial it all all at once?
it is more part of the number you wish to dial. So just dial it all at once.


we decided to leave the bright orange decor already in the entryway.
This happy hue brightens that small, dark space right up!
yet very different than the fun tropical tree decor that we created at the old house!
The first thing I did was get some orange polka dot scrapbook paper.
and it came on this COOL oval-shaped plastic hook. So I saved the hook!
I used it as a pattern to trace and cut out ovals to use as paper ornaments.
vintage white thread-wrapped balls, and some glass clip-on birds.
We also picked up two new sets of four ornaments that look like owls!
Seriously, it even looks good in a blurry shot!


Beautiful property with Views in the Private Laguna Vista Estates Sub Division. The 2.015 acres has a shared well and power to the lot line. The lot is bordered by the Bureau Of Reclamation in the Heron Lake area. Lake is walking distance from property. One of the few lots that is bordered by the BOR. Property is set up as a camp site and would make a great home site. Having power and water is a huge plus. Deer, Elk and Turkey call this place home as well. Sub Division offers its own Volunteer Fire Department along with its own community center with year round access. The inlet to the lake is the Willow Creek that has some great fishing also. Come up to the Beautiful mountains of Northern New Mexico for the best outdoor recreation.


Garry Kasparov and Anatoly Karpov will play a 12 games match from 21 to 24 September, 2009, in Valencia. It will consist of 4 rapid (or semi rapid) and 8 blitz games and will take place exactly 25 years after the mythical encounter between the two players.
Anatoly Karpov revealed some important details about the match to the Russian newspaper Izvestia. Bellow is an excerpt from the interview, courtesy of e3e5.com. More related news.
Izvestia: Mr.Karpov, whose idea was to organize your matches with Kasparov?
Anatoly Karpov: I can't remember exactly, I only know that it was in May of this year. I met with Kasparov in Moscow to discuss various issues not directly related to chess. During the conversation it came up that we have anniversary of our world championship match. Then we decided to meet over the board to celebrate the occasion.
Q: Does that mean that you and your great rival meet very often?
A: Of course, not very often. But perhaps a few times a year we speak about various subjects.
Q: A couple of years ago after the arrest of Kasparov you saw him in the detention center and even tried to bring a chess magazine in. Was that an act of solidarity?
A: That was the least I could do. In that situation, the police clearly overreacted. So Kasparov and his supporters did not have the permission to come out on the streets? It should normally result in a fine, but not with a three days arrest. Yes, Kasparov holds very sharp political opinions, but his actions did not deserve that response.
Q: How many games planned?
A: The initial plan is to play for about six months in all countries where we once had world championship matches. That is, Spain, Russia, Great Britain, France and the United States. Actually, the first rapid match was planned for London, but the negotiations on the organization took a bit longer, and the Spaniards were glad to jump in and take the initiative.
Q: But why Valencia? Your most dramatic match for the title took place in 1987 in Seville.
A: Partly because Seville never had a rich chess tradition. Valencia is entirely different, it is enough to say that one of the city squares is named after me. In addition, Rita Burberry Nola, the mayor of Valencia who manages the city for the last 18 years, loves sports. It is not by incident that they have established a powerful football club, which recently was Spanish champion.
Q: Where will be the playing venue?
A: In the new Opera, in one of the rooms which accepts about 350 spectators. Naturally, it will be packed. Large screens will be installed outside of the building and the passers will be able to watch our game. Incidentally, just before our interview, it has been confirmed that our next match will take place in the Louvre, Paris.
Hopefully, early next year we will play another match in Moscow.


text:
Q: append() method loops on all elements of a list in python I'am using namedtuples object to create Nodes and Graphs to represent a network. The goal is to allocate resources of a main network, referred to as network, to smaller networks, referred to as requests.
A request is considered fulfilled when all its node are associated to a network node and the "shape" of the request is kept, as shown on image below. Request is represented in red
Example of fulfilled request
Nodes items are built as follow :
Node = namedtuple('Node', 'name val alloc', defaults=[[]])
Graphs items are built as follow :
Graph = namedtuple('Graph', 'nodes edges', defaults=[[], []])
Here are the network and request from the image, built in Python
a = Node('a', 10)
b = Node('b', 6)
c = Node('c', 5)

Vnode = namedtuple('Vnode', 'name val')

x1 = Vnode('x1', 3)
y1 = Vnode('y1', 4)

Graph = namedtuple('Graph', 'nodes edges', defaults=[[], []])

vne = Graph([a, b, c])

I tried to isolate the code that doesn't work as intended, here it is :
def allocate(node, node_vnf, visited, visited_vnf, to_visit, to_visit_vnf):

    # node_vnf = node to place;
    # to_visit = network nodes that haven't been visited;
    # to_visit_vnf : request nodes that haven't been visited

    if node_vnf.val <= node.val and node_vnf not in visited_vnf and node not in visited:  # Are there enough resources free on the node ?

        node.alloc.append(node_vnf) # We had the request node to the network node attribute alloc

        node = node._replace(val=(node.val-node_vnf.val)) # change the value of network node
        visited_vnf.append(node_vnf)
        visited.append(node)

        return node
    else:
        return node

In the function above, append() applied to node.alloc, attribute alloc of Node object node, loops on all nodes of the network instead of just adding node_vnf at the end of node.alloc.
Does anyone have an idea, on why append() method does work as intended ? I tried using insert() too, but it acts the same.
Please let me know if any information on the subject is missing or isn't clear.
Thanks in advance for your help :)

redpajama_set_name: RedPajamaStackExchange


text:
tabi Arts
Tobe Porcelain Shop
Delivery and Refund
Tobe studios/makers
TICEP
TICEP Archive
Ascending Colours – 3rd & 4th December 2022
photograph by Bob Walkden
5 creative minds – 2 potters, 1 printmaker, 1 writer/cook and 1 curator – working together to fund raise for refugees around the world.
Our pop-up exhibition Ascending Colours sold our artworks, and the profit was donated to Choose Love – a charity organisation that works for refugees globally.
At: Regent Studio, 8 Andrew Road, Unit 3b, London, E8 4QN
Participating artists;
Yasuko Arakawa – ceramics @yasuko.arakawa
Born in Kyoto Japan, Yasuko studied ceramics in London, and her inspiration comes from nature and time. The use of texture, form and colour to capture the qualities of earth, wind and water is encased in her hand-made ceramics which are designed for a contemporary lifestyle.
Yasuko creates tableware to be enjoyed in good company. She believes there's a story in every object – each object should be considered filled with warmth, kindness and stories.
She brings her deep appreciation of Japanese craft to her Hackney ceramics studio and classroom.
Visiting the studio:
All of Yasuko's classes are taught at her studio in Hackney Wick, Studio U, Unit 20, Main Yard 86 Wallis Road, London E9 5LN.
Annaleaclelia Tunesi – ceramics @annaleacleliaceramics
AnnaLeaClelia Tunesi (b. 1964) is an Italian ceramic artist based in London. She studied set design for theatre at the Accademia di Belle Arti di Brera in Milan, and worked as an art director in television production for eighteen years, between 1987 and 2005. In 2007, she returned to her studies, completing an MA in the History and Business of Collecting Art at IESA, Paris and Warwick University, UK, and obtained her Ph.D. in Museology from the University of Leeds in 2014. She had been working in ceramics throughout these years and began to formalize her practice by beginning evening classes with potter Sarah Walton in Sussex in 2000. While undertaking her MA, she completed a three-month internship at the Stefano Bardini Museum in Florence. The fragments collection from antiquity to Renaissance art, and the eclectic nineteenth-century taste of the art dealer, had a strong influence on her research surrounding shapes and their unfinished aspect. This led to an increased passion for ceramics, and in the last few years, she has decided to dedicate herself full-time to the production of her pieces. She works at her studio in Hackney.
Donna Shrestha – linocut prints @bibbitink
Donna Shrestha is a linocut printmaker working from her home studio in London. During her degree in illustration she found a passion for printmaking.The prints she produces reflect her interest in east and south Asian art. Her stylised and decorative work uses striking abstract patterns and bold colours that draw inspiration from the natural world.
Miki Iioka – food @axelriolondon
A business writer and translator by day, Miki Iioka is a self-taught cook, a cookbook aficionado and a food blogger the rest of the time. Although she grew up eating Japanese food and that is what she loves to cook whenever in Japan, here in London, where she has lived for the past 14 years, she enjoys exploring the more diverse food cultures, especially Mediterranean/Middle Eastern cuisines. She worships Claudia Roden, Yotam Ottolenghi and Sami Tamimi and intensively cooks from their books. She has developed recipes for a Japanese seafood company Abekame, using their products in whole new ways inspired by Mediterranean cooking.
Mamiko Karasudani – curation and Tobe pottery @tabimamiko
Born and bred in Japan, she then landed in London in her late teen. After she studied Humanities (BA) and Visual and Cultural Studies (MA) her career has spanned from working at independent galleries, fringe theatres and major museums in London to curating exhibitions in the UK and France. She has been working with the ceramic artists of Tobe over the past decade, and since 2019 she has been leading the TICEP (Tobe International Ceramic Exchange Programme) where she organised a resident artist programme in Tobe, and planned the sessions between artists in Japan and the UK.
She has always wanted to make an event to fund raise for refugees around the world, and for Ascending Colours she has teamed up with fantastic members who she feels positive and confident to make it successful.
2018 – London
tabs Arts participated with Tobe porcelain in three part exhibitions spanning throughout the year at Chalice Gallery.
flyer design; Stuart Bartlett
Our first exhibition in Paris was held in the heart of the city in conjunction with Zenzan Japanese Restaurant from 26th to 31st December 2017. Despite the freezing cold weather and rainy days the visitor turn out was amazing, and the exhibition opened up a few other opportunities such as the Yamato festival in April 2018.
Gold and silver special edition Shizuku cup by Eiryuji studio
Ms Yamada who was a star of the tea ceremony
Gensei studio
© 2023 tabi Arts

redpajama_set_name: RedPajamaCommonCrawl


text:
Owning Land
Pulse Question
Pulse Results
COMMERCIALFLIP
Land Lingo
Which Mapping Software Do You Use?
Outlining the Differences In WRP and CRP
Getting Real: Do I Need a Land Agent?
Pulse: Land Buyers Not Willing to Pay Over Appraised Value
Working forest conservation easements can make sense
Curtis Seltzer
Over the years, I've become less enthusiastic about conservation easements as they apply to timberland.
Among the mixed bag of reasons for my unease are:
1. Deliberate inflation of timber value to inflate the size of the easement value to inflate the size of the tax benefits available to the landowner;
2. Questionable assignments of environmental value to certain timberland tracts, which is the first hurdle in qualifying land for conservation-easement status;
3. Overly strict restrictions on cutting timber that have little, if anything, to do with protecting the environmental values of the tract;
4. A bias toward applying wilderness ("forever wild"; no-use) standards to non-wilderness lands in a way that doesn't benefit the environmental values that should be protected;
5. Easement donors who don't fully understand the long-term financial implications for spouses and heirs of severing a valuable, appreciating right in a property, particularly when it's one of their principal financial assets;
6. Revenue loss for local governments that reduce assessed property value to reflect the donation of the easement; and
7. Long-term reduction in the amount of land capable of producing wood products, broadly defined, which may or may not affect timber supply and prices in the future.
Still, I endorse the use of conservation easements for certain types of timberland and other lands. I work with clients who use them as part of their acquisition strategies. I'm not opposed to leaving private lands completely free of human intervention, though I think that usually carries the notion of protection too far and winds up putting important environmental values at risk.
While it doesn't address some of the issues I've listed above, a Working Forest Conservation Easement (WFCE) does address several important ones. A WFCE envisions timberland to be managed for timber production over a long period. This can involve annual timber-sale income in the case of a very large tract or income spaced, say, every 15 or 25 years, for smaller tracts of mixed-age, mixed-species woods. The emphasis is on long-term returns from sustainable management rather than a short-term emphasis of maximized revenue. Use restrictions that would impede managing the woodlands as a working forest are not imposed.
The rights that the WFCE limits relate to residential and commercial development. The value of these rights depends on the location of the property and other factors, but it could amount to as much as 50 percent of current fair market value. The value of the easement would typically include the estimated value of the development rights (residential, commercial, mineral) foregone along with the foregone value of merchantable timber not cut in the short run.
One version of a WFCE was developed to protect and work with about 2,200 acres of California redwoods in the Van Eck Forest. The concept was pioneered by the Pacific Forest Trust (PFT) whose goal is to preserve productive private forests for all their public benefits—the delivery of wood, water, wildlife and a well-balanced climate. PFT incorporated carbon storage in its management plan for both climatic and financial reasons. The forest generates income from the sale of both timber and carbon credits. (Laurie Wayburn, "THE VAN ECK FOREST: Carbon Markets and the New Economic Paradigm for Forest Sustainability," in James N. Levitt, ed., Conservation Capital in the Americas: Exemplary Conservation Finance Initiatives, Lincoln Institute of Land Policy/Island Press, 2010)
A WFCE generates income for the landowner; maintains significant, appreciating value for heirs; incorporates environmental values into its timber-management plan; continues timber production from a renewable resource in a sustainable manner; and offers the option of generating income from the timberland through carbon credits and hunting leases, if desired.
Making arrangements for the sale of the landowner's timber-stored carbon is a critical part of the PFT's approach. It's cumbersome and costly for small landowners to work through the Chicago Climate Exchange, but it's possible…and it may become easier in the future.
This content may not be used or reproduced in any manner whatsoever, in part or in whole, without written permission of LANDTHINK. Use of this content without permission is a violation of federal copyright law. The articles, posts, comments, opinions and information provided by LANDTHINK are for informational and research purposes only and DOES NOT substitute or coincide with the advice of an attorney, accountant, real estate broker or any other licensed real estate professional. LANDTHINK strongly advises visitors and readers to seek their own professional guidance and advice related to buying, investing in or selling real estate.
The Nuts and Bolts of Conservation Easement Properties
Explaining a Conservation Easement to a 12 Year Old
What Could a Donald Trump Presidency Mean for the Land Market?
Curtis Seltzer is a land consultant, columnist and author of How To Be a DIRT-SMART Buyer of Country Property and Land Matters: The "Country Real Estate" Columns, 2007-2009.
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Jonathan Goode says:
Curtis, good article and I will definitely look into the "working" conservation easement a little deeper. This makes a lot of sense from a sustainability and common sense standpoint.
One issue with carbon offsets is that the CCX has really tanked in the past year. I was the president of a company in Alabama that was registered as an aggregator with the CCX. The market dropped from $7 per metric ton of CO2 when we started to the present price of $0.10/metric ton. Today (4/13/10) no offsets were even traded on the CCX platform.
Thanks for the insights on these types of easements. Owners have more options and stronger convictions when buying land, and this may serve them well.
Fixing nonpoint-source water pollution may require new fencing
Timberland Investing: Selling Timber Rights is Another Way to Skin a Cat
What would be your reason for buying land in 2022?
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text:
Q: Calculate Km with latitude and longitude of different DataFrames Python Pandas I have 4 Dataframes (ticket_data.csv, providers.csv, stations.csv and cities.csv)
In stations.csv I have 2 colls called o_city (origin city) and d_city (destination city) those two colls gives me the id of the city i need to look for in cities.csv
In cities.csv I have the lat and long of each city.
How can i calculate the distance between o_city and d_city for each ticket ? I tried to use pyproj but I didn't find a way to make it work with each ticket..
Screenshot of csv files :
ticket_data.csv
cities.csv

A: Welcome to StackOverflow!  In your cities dataframe, assuming here it is called city_df; for each row you can use something called the haversine distance formula from Euclidean geometry to calculate the distance between two coordinate pairs on Earth's surface.  Here is an example of some dummy Python3 code of roughly how you may go about this (just using two pairs of coordinates for ease of communication):
from haversine import haversine

distance = haversine((city_df[origin_lat][0], city_df[origin_lon][0]), (city_df[destination_lat][0], city_df[destination_lon][0]))

The coordinates must be in decimal degree notation as in 43.9202 instead of 43* 38" 67' notation.  Given this, the output value of distance will be in km units.
Hope this helps you get closer to solving your problem!
P. S. - you may need to install haversine, as it is not in the standard libary


text:
Q: Delete all rows of a pandas dataframe where certain conditions are met over all columns My dataframe looks like this:
I want to delete ALL rows (red marked in the picture) where every column has a value like:
"", "nan", "NaT"

I tried several things like dropna, replacing and dropping, but I am can not make it work to delete it.

A: Use:
mask = df.fillna('').isin(["", "nan", "NaT"])

df = df[~mask.all(axis=1)]


Governor tackles education by zeroing in on judiciary.
Gov. Sam Brownback now reigns over a Kansas Legislature with fellow conservative Republicans in control of the House and Senate.
Gone is a moderate Republican-Democratic coalition that at least tried to serve as a check on GOP conservatives' often misguided measures � to include their relentless attacks on education.
In his State of the State address Tuesday, the governor cited education as a cornerstone for economic prosperity. But he's since pitched a modest increase in education funding that's nowhere close to what's necessary.
A recent court ruling said the Legislature has failed to meet its K-12 school funding duty under the Kansas Constitution. The three-judge panel in Shawnee County District Court said Kansas must boost its annual aid to public schools by at least $440 million to meet its constitutional responsibility to provide a suitable education for every child.
Understandably, the court found it difficult to accept claims that the recession made recent cuts to schools necessary in a state still in position to implement massive tax cuts that will reduce income.
Brownback denounced the ruling, and made it clear he wanted to change court involvement in school funding.
In Tuesday's speech, he promoted changing the state constitution to let a politically-motivated Legislature determine how much money is needed for schools � a clear path to even deeper state cuts to education, and an inevitable rise in property taxes at the local level to support schools.
Brownback also would scrap Kansas' nonpartisan, merit-based judicial selection process in favor of either direct election of judges to the Kansas Court of Appeals and the Supreme Court, or a model in which the governor would appoint judges with Senate confirmation � in essence letting him hand-pick judges sympathetic to his ultraconservative fiscal and social agenda.
It's little more than a plot to control the judiciary, and part of a blueprint calling for control of all three branches of state government as a way to forward an extreme ideology without checks and balances.
And, it's frightening. Kansans who rightly view balance and compromise as hallmarks of the democratic process should be very concerned.


T om Virgin believes in the power of art and how it can help create a better, more connected community. The Miami-based high school teacher and activist is also a printmaker and artist who works in woodcuts.
In addition, he's the founder of Extra Virgin Press in Little Haiti, which makes letterpress book arts and broadsheets. Letterpress is the key to the artistic niche Virgin has carved out for himself. In the age of digital media and imagery, letterpress relief printing is an old-fashioned and labor-intensive craft.
Using letterpress, Virgin came up with a fascinating project, a collection of broadsheets -- single-page sheets, like the old broadsides used for disseminating news of the day -- for which he asked writers to submit extremely short poems or works of fiction.
But speed has no part in the actual process at all, says Virgin. The time to make them is what makes the printed works important. "You really have to choose what you'll print," he explains.
Virgin has now crafted letterpress posters for the Little Haiti Book Fair, and for artists showing at the Emerson Dorsch gallery and PAMM; he also makes book covers and artists' books. His own artwork has been shown at galleries, libraries, and universities.
Virgin was also instrumental in the SWEAT Broadsheet Collaborative, which starting in 2008 brought together 46 visual artists and 40 writers from South Florida, and eventually resulted in 78 broadsheets made from letterpress, silkscreen, etchings, and other media. Some of them have since been shown in spaces from Portland to Minneapolis, and numerous locations from Palm Beach down to the Miami-Dade College Kendall Campus.
The new space of Extra Virgin Press opened on NW 2nd Avenue in Little Haiti after receiving a 2015 Knight Foundation arts grant. Along with some of the broadsheets and artworks, there are two presses, and it is exciting to watch physical printing in progress during a visit.
Across the street, Virgin can also observe the lively neighborhood that is rapidly being displaced by gentrification and development, something that concerns him as well. But, he says, the arts can create a conversation in this current difficult climate.
His conversation is not isolated to South Florida. A native of Detroit, Virgin spends much of the summer in the small city of Red Wing, Minnesota, at the Anderson Center at Tower View, an arts and residency center along the Mississippi River at the Tower View estate of Alexander Pierce Anderson, a botanist who created the first "puffed" rice and wheat cereals developed under the Quaker brand.
He says he'd now like to bring these regions together. "I have students who have never been out of Miami," he explains. "I grew up in the Midwest and want to share that world with them." It is just one part of the latest mission for a man who never seems to sleep.
He adds that Extra Virgin Press's first portfolio, Home/s, is to be purchased by PAMM and is already in the Jaffe Center for Book Arts at Florida Atlantic University in Boca Raton, the University of Miami Special Collections, and the Frost Museum at Florida International University.
ome/s was the first Extra Virgin Press community project, and included artworks from the paired combinations of writer Danticat and artist Laura Tan; poet McGrath and artist Pip Brant; and poet Leonin and artist Adler Guerrier, among others. They were asked to offer views on "our common home" in the form of literary broadsheets.
Although a printmaker and wood carver for 40 years, Virgin says he first dabbled in letterpress -- in Silver Springs, Maryland, in 2004 -- because he was interested in the various ways that print could be produced. He came to realize that creative and tactile text could be art.
After moving to South Florida, he developed a long relationship with the Jaffe Center, which is a hub for printing, as well as bookmaking. Founded by Arthur Jaffe, who had built a large collection of limited-edition artists' books, the center holds workshops on book binding and paper decoration, and has several presses. Virgin found a home there for print making and a mentor as well; Jaffe, who died in 2015, had bought his first book.
Now Virgin would like to continue the tradition with workshops here in Miami, and is generally inviting the community to come see the stories that are revealed in all the prints. After all, he says, whether you're a writer, a visual artist, or a printmaker, it's all about the tales you tell and how they help us understand each other in creative and powerful ways.


Posted on July 19, 2018 by Kevin Geran Posted in Plumbing	.
The difference between having to choose a good plumber and having to choose a carpenter, architect or painter is that the plumber is usually called in case of an emergency. This means you may not have much time to look around. Emergency plumber Adelaide is there to help you all around Australia. Anyway, here are some good tips on how to find a good plumber for all situations.
Usually, the best route is the personal recommendation. In this way, you can at least review the plumber in advance and get enough information to make an informed decision. Of course, if your plumbing leaks or your toilet is expelling its contents, you may not have much time to look around for advice.
You will be able to search for registered plumbers in the postal code area. These are plumbers who have been reviewed and meet certain criteria. The next step will be to start making some calls.
How long they operate, if they have premises, you can visit. A mature plumber will not disappear during work.
Have they done similar work before?
Do they have insurance to pay for your property (and the property of your neighbors)?
Do they guarantee their work? Is this insurance guaranteed? This means that if they are closed, you will still be protected.
Is the plumber a member of a professional trade organization? If you have time, please contact the relevant trade agency and see if they are currently registered.
Of course, if it is an emergency, you may not be able to do all of the above. But it is good to look for professional plumber St. Agnes.
What is their summoning fee?
What is their hourly rate?
How much does a good plumber charge?
It all depends on it. There is no standard guide for how much the plumber can charge.


text:
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Missed you
A new trade deal has FOMO as its secret sauce
The aim is to make President Donald Trump feel like he is missing out
Finance and economicsJul 6th 2019 edition
THE MOTIVE force behind trade deals is supposed to be "FOMO"—the fear of missing out. If negotiators fail to grab new markets for their exporters, the theory goes, rivals may snap those markets up first. On June 28th two trading partners seized better access to each other's markets as Mercosur, a customs union comprising Argentina, Brazil, Paraguay and Uruguay, agreed to a new trade deal with the European Union. An EU press release gloated that European companies would gain an "important head start into a market with an enormous economic potential".
The details have yet to be published. But the pact should improve market access for French cheese, Brazilian orange juice and Argentine fish, as well as car parts made in Europe, which now attract Mercosur tariffs of 14-18%. European companies will be eligible to compete for government contracts within Mercosur. Customs procedures will be simplified. Based on current trade patterns, the annual bill for tariffs on Mercosur's imports from the EU should fall by over €4bn ($4.5bn), more than four times the equivalent sum for the deal the EU recently signed with Japan.
Though 9% of Mercosur's tariff lines, and 5% of the EU's, will remain above zero, a "standstill" clause commits the members not to raise any of the tariffs above an agreed rate. In effect the EU has insured itself against the South American countries swinging back towards their habitual protectionism. But there was no talk of backsliding as the deal was announced. Brazil's government called it a "bridging agreement", intended to facilitate further agreements with other countries. Shunko Rojas, until recently one of Argentina's negotiators, recalled scepticism about Mercosur's ability to close trade deals. But this one, he said, should send the message that Mercosur is open for business.
Indeed, Mercosur may be thinking of the EU deal as a model for others. Emily Rees of Trade Strategies, a consultancy in Brussels, notes the overlap between Mercosur's other negotiating partners and countries with which the EU already has trade agreements. Potential Mercosur deals with Canada, South Korea, Singapore and EFTA (Iceland, Liechtenstein, Norway and Switzerland) could be designed to complement the agreement with the EU, making it easier for components to slip into global supply chains. She interprets the move as Mercosur turning away from "import substitution", the failed development model under which it kept out foreign products in the hope that local production would thus flourish.
In the two decades that the EU and Mercosur have been talking, the world has changed. When they started the EU was indeed fuelled by FOMO—specifically, the fear of being beaten to the South American bloc by a free-trading United States. But America's attitude to trade is not what it was back then, and the EU's motivation has consequently changed too.
FOMO is still involved—but it is no longer the EU that feels it. Instead the trade bloc may be hoping to inspire it in the Trump administration, which has been threatening—or applying tariffs to—almost all its trading counterparts, including the EU. As well as the looming threat of tariffs on cars and car parts unless the EU reaches a deal, on July 1st America said it might impose new tariffs on $4bn-worth of imports from the EU as part of an ongoing dispute over aircraft subsidies. And even if America does not feel a trickle of fear at the prospect of falling further behind the EU, which leads the world as signatory to the largest number of trade deals (see chart), perhaps other governments might get the message. On June 30th the EU signed a trade deal with Vietnam, days after Mr Trump threatened the country with tariffs.
It would be premature to predict a further flurry of trade agreements. The one between the EU and Mercosur may have been agreed during a rare window of opportunity when the governments of Argentina and Brazil were both in favour of economic liberalisation. That window will close in October if Mauricio Macri is not re-elected as president. Further deals involving Mercosur would become less likely, and the one with the EU might not be ratified. Even now, the Argentine fact sheet accompanying the EU-Mercosur deal boasts about how much more slowly tariffs would be lifted relative to the EU's other trade deals. Nor is ratification certain at the EU end, since national parliaments may each have a veto.
Hunger for a slice of Europe's agricultural market drove Mercosur's negotiators towards agreement. (The beef quota they secured was modest because the EU pleaded the necessity of saving some goodies for counterparts in future deals.) Extra quotas of beef, dairy or pork are also alluring for America, which is negotiating with the EU too. But the EU is insisting that they are off the table. However good it feels to stand up to Mr Trump, free trade is still a hard sell.
This article appeared in the Finance and economics section of the print edition under the headline "A new trade deal has FOMO as its secret sauce"
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text:
Q: When do Salarians mature? It is noted in the ME wiki that Salarians mature much faster than humans.
Given that they live typically to an age of 40 years they would likely mature a lot earlier than a human, but how much less?
At what age is a Salarian considered an adult?

A: Can you compare to human years?  Given the age of puberty is around 13ish years and the average life expectancy of human is what? 80?
13/80 = x/40 which would be 6.5.  Numbers might be different, since humans live longer and mature later/earlier in the ME universe.

A: I don't think they ever say exactly when a salarian is considered an adult, but we can do some fuzzy math to get a rough idea:
According to the Mass Effect Wiki, Mordin Solus was born sometime in the 2150's, and was recruited by Commander Shepard in 2185.  That means that he was between 25-35 years old when he was recruited.  We'll take the average and say he was born in 2155, so he's 30 "now."  Before that time (working backwards) he was a doctor in Omega, a member of the Genophage renewal STG team, a solider/commando of some kind before qualifying for STG (giving rise to the amazing quote "Have killed many, Shepard. Many methods. Gunfire, knives, drugs, tech attacks, once with farming equipment."), and then he must also have been a student for a while before becoming such a respected scientist.
Mordin's operation in Omega seems well-established, but given that only certain people seem to have heard of him, we can assume it's fairly recent.  Call it 6 months.  The way Mordin talks about his fond memories of the Genophage project, it sounds like a more substantial amount of time, probably at least a year, maybe 2-3.  His military career (that quote again) seems to have gone on for long enough that he's seen plenty of combat despite living in a generally peaceful era, so call it 4-5 years of service.  He's obviously a genius even among salarians, so his education may have been more rapid than normal (the salarian Doogie Howser), but even he had to have gone through at least a few years of study to know so much in so many fields, so call it 3 years of "graduate study" after whatever standard education salarians go through.
Now, these numbers are admittedly my personal estimations rather than hard facts from the canon, but given those numbers, Mordin started "graduate school" when he was about 18, equivalent to a Human of 23-24.  Thus, an 18-year-old Human is probably equivalent to a 14 year old Salarian, maybe younger if I'm underestimating the length of any of those phases of Mordin's life.
So I'd say salarians probably "come of age" around 13-14.
But again, that's just an educated guess.
UPDATE (Oct 2014): I just noticed a line from ME2: Mordin mentions that a nephew recently got tenure at a university, and that he just turned 16.  He's described as a "promising geneticist," but Mordin specifically says that he's not a genius or a prodigy.  (Or rather, he is, but the timing of his getting tenure is unrelated.)  Unless the Salarian academic world is radically different from our own, this likely means that Salarians come of age MUCH younger than my previous estimate.
Given the time it would take for a Salarian to go to college, probably grad school as well, then serve as a professor before achieving tenure, that means Salarians probably come of age more in the 7-9 year range.
Again, just an educated guess, but with more data from the canon comes a more reliable estimate.


Click the button "Get started, it's free".
Register new account with temp mail.
Inside " My account " click to "Get More Free Data" and tweet now.
And you get another 1000MB.
The Twitter Promo also works great.
It worked nicely. How does this vpn compare to ipvanish or windscribe?
Works well. However, if someone uses a 'temporary' twitter account to get that additional 1 GB, it might get the entire TunnelBear account blocked.
I've truly liked TunnelBear, and have only needed to use from within the free 500 MB offering thus far upon our lap tops & tablets (my wife for online purchases, & I for miscellaneous activities such as playing World of Tanks Blitz).
If we find we'll need more data, I may soon be "Tweeting" about more than our MalwareTips Giveaways!
looks like it stopped working I am not getting 5500 MB.
You have to clear browser cache or use the private window for it to work. I am amazed this promo is still working. I created mine several months ago & after initial problem of same nature once, I got it work. 6500MB in account. I think you have to tweet every month(?) for the extra 1GB but could be different.
does anyone know how long you will have the 5GB, is it for life or is it for 1 year?
I have not yet past 1 year since signing up hoping its more than that!
I would never complain if I ever get 500 GB myself, let alone more than that.


text:
Cupra  puede referirse a:
 Cupra,  marca española de automóviles de gama deportiva, perteneciente al Grupo Volkswagen
 Cupra Formentor, suv deportivo
 Cupra, diosa de los pueblos itálicos
 Cupra Marittima, localidad y comuna de la provincia de Ascoli Piceno, región de Marcas, Italia
 Cupramontana, localidad y comuna de la provincia de Ancona, región de las Marcas, Italia

redpajama_set_name: RedPajamaWikipedia


text:
runner = require("./_runner");

runner.runTest("basics");
runner.runTest("syntax");
runner.runTest("filters");

// runner.runTestDirectory( "render", "basics" );

redpajama_set_name: RedPajamaGithub


text:
Ringling Bros. Settles Elephant Lawsuit
By Bryan Robinson
March 1, 2001 -- Thanks to an out-of-court settlement, some retired elephants from Ringling Bros. and Barnum & Bailey will have a new home in an animal sanctuary provided by one of the circus' harshest critics.
On Monday, Ringling Bros. and the Performing Animal Welfare Society announced they had settled a federal lawsuit in which PAWS officials accused the circus of stealing documents and spying on them to discredit the animal rights group.
In its 16-year history, PAWS, which is based in Galt, Calif., and provides homes for retired and abused performing creatures and wildlife, has frequently criticized Ringling Bros. for its alleged abuse of elephants and other animals.
Ringling Bros. agreed to donate a "number" of retired Asian elephants to PAWS over the next three years and provide financial assistance for their long-term care. Neither side would discuss other specific terms of the settlement of the lawsuit, filed last year in the U.S. District Court for the Eastern District in California.
Noted Adversaries, Common Ground
Ringling Bros. refused to comment on the allegations. In a statement, circus officials said the settlement was "an example of cooperation between two organizations that have differing philosophies but who share the same goal of providing continued care to performing animals when they retire."
PAWS founder Pat Derby said she was pleased and delighted.
"We were surprised [by the settlement]," Derby said. "Sometimes when you're in a conflict with someone for so long, you forget that no matter what, you always have some common ground, in this case the care of the elephants. We just care about the elephants."
Ringling Bros. owns more than 65 Asian elephants between the ages of 1 and 58 and says it has worked with the animals for more than 130 years. PAWS cares for more than 75 exotic animals, including four elephants, at its Galt facility and is building a 2,300-acre sanctuary in San Andreas, Calif., which is expected to open in 2002.
Derby says the facility will have Jacuzzis and "plenty of open space for the elephants to play in the mud and enjoy the rest of their days."


The Congressional Caucus on Black Women and Girls hosted a town hall at the Library of Congress Wednesday to address what they characterize as a national epidemic of missing black children. The group, founded by Kelly, Rep. Yvette Clarke and Rep. Bonnie Watson Coleman in 2016, consists of more than 20 lawmakers working toward solutions to challenges impacting black women and girls.
The town hall came amid calls for federal assistance to help locate missing African-American girls whose profiles are posted almost daily on the Washington Metropolitan Police Department's Twitter feed. In 2014, the Black and Missing Foundation reported that 64,000 black women and girls were missing nationwide.
But activists, law enforcement officials and political leaders at the town hall said media coverage and legislation does not reflect that reality. After hearing the data, House Minority Leader Nancy Pelosi said it is "such an injustice" that women and girls of color are more likely to go missing.
Panelists wanted to dispel the idea that all missing black girls are runaways from challenging backgrounds involved in illicit activities and said any young person who is active on social media can find themselves at risk of being abducted.
The event's speakers said Congress needs to provide resources so that multiple agencies — police departments, health care institutions, courts and social services — can better collaborate to find missing girls.
"We miss so many young ladies that are being exploited because we don't see African-American girls as victims, we see them as misbehaving," she added.
Caucus members responded pledging to advocate for more funding, housing and training to aid those on the ground responding to the issue.


text:
KDC is een afkorting die kan staan voor:
 sleuteldistributiecentrum, een Key distribution centre
 Katholiek Documentatie Centrum aan de Radboud Universiteit te Nijmegen.
 Karen Demirchyan Complex, een sportzaal in Jerevan.


The Penguins came into tonight's game against the Rangers with a chance to pull within 2 points of 2nd place in the Metro Division with a game in hand. The offense was red hot, Sidney Crosby had several active scoring streaks, and the Rangers were without key contributors Ryan McDonagh and Rick Nash. It was a golden opportunity for Pittsburgh, but Henrik Lundqvist was more than up to the task by stopping all 34 shots in propelling New York to a 3-0 shutout. The Penguins dropped to 6 points behind the Rangers in the standings and find themselves tied for the final wild card spot with the New Jersey Devils. It was bad timing on the loss for a Pittsburgh team that came into the night having won 6 of their previous 7.
The opening period was a fast-paced, back and forth affair that didn't result in much offense. Pittsburgh led the way in possession, but it didn't translate to the scoreboad. The Penguins got good pressure killing off a Kris Letang hi-sticking pentaly about midway through the period, and managed to kill of the Rangers' power play, but New York was able to get on the board seconds later. Marc-Andre Fleury appeared to lose his footing while hugging the post on a Tanner Glass shot from the left boards, and Kevin Hayes managed to grab the rebound, skate his way to a clear shot, and shoot it into an open net. The Pens got a power play of their own on a Dylan McIlrath interference penalty, but they weren't able to convert any of their chances and the game went to intermission with New York in front 1-0.
The Pens came out down a man in the 2nd as Trevor Daley remained in the locker room after crashing hard into the net in the first period, but they almost tied things up minutes into the period. Connor Sheary took a Kevin Porter feed in the neutral zone and split the defense to get 1-on-1 with Henrik Lundqvist. He beat Lundqvist high on the glove side, but his shot pinged harmlessly off the post. The game continued in much the same manner as the first, with neither team being able to sustain much in the offensive zone and the game going back and forth. The Penguins continued to turn up the pressure on the Rangers, and the team got a great chance late in the period as Bryan Rust and Tom Kuhnhackl came in on a 2-on-1, but the Kuhnhackl one-timer had no chance and was turned aside to the corner.
Unfortunately, it just happened to be one of those nights. The refs were calling a tight game, and Lundqvist was more than capable of handling things at even strength. The Penguins needed a good push to start the 3rd period, but unfortunately it was Dominic Moore giving the Rangers an insurance goal 4 minutes in. Moore and Chris Kreider came down the ice on a 2-on-1, and Moore was able to snipe a shot past Fleury from the top of the circle. Scott Wilson drew an interference call on Kreider midway through the period, but the power play again wasn't able to beat Lundqvist. A Jesper Fast empty net goal sealed the deal and ended any hopes of a similar 2-0 comeback that was successful Saturday night against the Panthers.
The Penguins lost the game despite owning an advantage in possession, controlling a score adjusted 55.3% of the 5-on-5 shot attempts. It didn't translate into goals, and the Pens were shutout for the 5th time on the season. Pittsburgh will travel to Carolina to face the Hurricanes Friday night. They'll need a win to maintain the pace in the playoff race, and a regulation loss will bring the Canes to within 2 points of the Penguins in the standings.


Lucky Patcher is a great tool for Android to hack Android apps and games, block ads, modify app permissions, backup apps etc. Many users don't know how to use Lucky Patcher app properly. So, we have created these instructions for you. See how to download and install Lucky Patcher.
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I am a multi instrumentlist songwriter and producer.
I am currently working and developing various musical artists.
I run a music service and a working musician.
I am looking for a keyboard/Synth player for songwriting and recording sessions.
Looking for the right person to develop a strong songwriting team within the music industry. Developing new singers.
If you are interested please contact me with your links and experience.


text:
Ламберт, (†836) — граф Нантський і префект Бретонської марки між 818 і 831, герцог Сполетський з 834. Разом з Людовиком I Благочестивим у 818 брав участь у поході проти бретонців, які проголосили Морвана своїм королем.

У 831 підтримав повстання Лотара I проти Людовика, за що був висланий до Італії, де отримав у правління герцогство Сполетське. Помер у 836 році, що був багатий на епідемії.

Примітки

Джерела
 Wickham, Chris. Early Medieval Italy: Central Power and Local Society 400—1000. MacMillan Press: 1981.

Середньовічна Італія
Герцогство Сполетське
Маркграфи Бретонські
Правителі Європи IX століття


English-Greek dictionary for high school and college students. It includes new words and it has many examples. 50,000 entries and 20.000 idomatic espressions, phrazal verbs, etc.
Fytraki publications. 992 pages. Hardcover.