It's been a while since I've indulged in a MC Romance, and the prospect of one with two 'born to the club' characters who come from different clubs finding their way together, despite the many issues inherent in their choices was too much to pass up. Per the synopsis, Ryan Michele clearly states this title works without having experienced the earlier series, and that promise held true: I wasn't missing large pieces of information, and while I'm curious about the start of the Ravage MC story, my unfamiliarity with it didn't impact this listen in any way. There is a significant (and I felt over-played) series of descriptions that 'reinforce' the MC club's creeds and 'badassness', but for a newbie to the genre, or someone unfamiliar with the workings of a club, the background does set a tone for the story: darker, not always legal dealings, foul mouths, and some ruthless decisions.
Cooper Cruz was born into the Ravage MC, he's enjoying the brotherhood and feeling of belonging, even as he is always thinking of ways to launder money and improve the club's future. He's one who understands the creed and expectations of members, and appreciates the brotherhood and relative freedom that he has to pursue his own life and interests, knowing there is a safety net and acceptance back at home. Bristyl Daniels has a different experience as the daughter of the VP of the Sinister Sons MC: as a girl – while the acceptance and protections are afforded her, she's always feeling controlled and guided: not allowed to make her own choices because of the 'eyes' always on her from the club members. Not always carefully controlled, however, she sneaks off to see her favorite band at a rally in her town, and the story starts to pick up steam.
Cooper and Bristyl meet and are instantly attracted. She finds him hard to resist – and then things get ugly. Trouble with a capital T puts Bristyl at risk, and Cooper, being more than a bit alpha, badass and intrigued by this girl, steps in with others from the club – bringing all sorts of attention from the wrong people, including the Sinister Sons. Two people, bred to different rival clubs with their own rules, guidelines and alliances is nothing to mess with – but Cooper doesn't care. He wants Bristyl and from her reaction, that feeling is mutual – and he'll suffer the consequences to get to know her better and see if there is more than an electric attraction between them.
Unlike many other MC romances, the club and the often arcane and misogynistic attitudes don't play a huge part: this is two people wanting to explore an attraction to see if there is something real beneath the hormones. Slowly they build a relationship and learn to trust in one another, despite the real dangers offered by their connection. The more they get to know one another, the stronger their bond: choices must be made, but can they survive those choices to live a life together – especially since they have built something solid and lasting, even with the 'melt the pages' chemistry? A wonderful introduction to the series with both Cooper and Bristyl coming alive on the pages, bonding and encouraging readers to cheer them on despite the difficulty.
Narration for this story is provided by Joe Arden and Lucy Rivers – and together as Cooper and Bristyl their voices feel age-appropriate and work well together. Both are able to add a touch of emotional nuance that enhances their moments of angst or passion, and conversations and interior monologues from each character feel natural. The few secondary characters that enter the story feel more like a retelling of the moment from either Cooper or Bristyl, none are distinctly different in tone or delivery that would have indicated to the listener a new character has arrived. A workmanlike performance from both here, presenting the words on the page and adding appropriate emotional impact, adding to the interest and keeping me engaged.
Great review here. I have enjoyed quite a few MC romances but haven't read too many lately. I like that the focus is on the relationship and not the club.
I have my moments with them – this was intriguing from the relationship standpoint – but I just finished one from Laura Kaye that did similar – but managed to work in some suspense and tension in the plot – more than here.It's kind of what mood strikes me — 🙂 Thanks for stopping in!


text:
A novel potential effective strategy for enhancing the antitumor immune response in breast cancer patients using a viable cancer cell‑dendritic cell‑based vaccine
Mona S. Abdellateif
Sabry M. Shaarawy
Eman Z. Kandeel
Ahmed H. El‑Habashy
Mohamed L. Salem
Motawa E. El‑Houseini
Affiliations: Medical Biochemistry and Molecular Biology Unit, Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11976, Egypt, Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo 11976, Egypt, Department of Pathology, National Cancer Institute, Cairo University, Cairo 11976, Egypt, Department of Zoology, Faculty of Science, Tanta University, Tanta, Gharbia 31511, Egypt
Published online on: May 4, 2018 https://doi.org/10.3892/ol.2018.8631
Dendritic cells (DCs) have been used in a number of clinical trials for cancer immunotherapy; however, they have achieved limited success in solid tumors. Consequently the aim of the present study was to identify a novel potential immunotherapeutic target for breast cancer patients through in vitro optimization of a viable DC‑based vaccine. Immature DCs were primed by viable MCF‑7 breast cancer cells and the activity and maturation of DCs were assessed through measuring CD83, CD86 and major histocompatibility complex (MHC)‑II expression, in addition to different T cell subpopulations, namely CD4+ T cells, CD8+ T cells, and CD4+CD25+ forkhead box protein 3 (Foxp3)+ regulatory T cells (Tregs), by flow cytometric analysis. Foxp3 level was also measured by enzyme‑linked immunosorbent assay (ELISA) in addition to reverse‑transcription quantitative polymerase chain reaction. The levels of interleukin‑12 (IL‑12) and interferon‑γ (IFN‑γ) were determined by ELISA. Finally, the cytotoxicity of cytotoxic T lymphocytes (CTLs) was evaluated through measuring lactate dehydrogenase (LDH) release by ELISA. The results demonstrated that CD83+, CD86+ and MHC‑II+ DCs were significantly elevated (P<0.001) following priming with breast cancer cells. In addition, there was increased activation of CD4+ and CD8+ T‑cells, with a significant decrease of CD4+CD25+Foxp3+ Tregs (P<0.001). Furthermore, a significant downregulation of FOXP3 gene expression (P<0.001) was identified, and a significant decrease in the level of its protein following activation (P<0.001) was demonstrated by ELISA. Additionally, significant increases in the secretion of IL‑12 and IFN‑γ (P=0.001) were observed. LDH release was significantly increased (P<0.001), indicating a marked cytotoxicity of CTLs against cancer cells. Therefore viable breast cancer cell‑DC‑based vaccines could expose an innovative avenue for a novel breast cancer immunotherapy.
Breast cancer is the second-leading cause of cancer-associated mortality among women worldwide (1) and constitutes 22.9% of cancer cases in women (2). In Egypt, it was reported that breast cancer represented ~38.2% of female malignancies (3). Despite advancements in treatment strategies, metastatic breast cancer remains incurable, with available therapies predominantly aiming to provide symptomatic relief and extend the overall survival time of the patient (4).
The development of effective vaccines for specific tumor cell antigens is uncomplicated; however, this approach has achieved limited success in solid tumors, particularly in the case of breast cancer (5). This is due to the number of breast cancer cell subgroups, which vary in morphology, biology, behavior and response to therapy (5). Constructing an effective, reliable, tolerable and safe cancer vaccine is the core principle of cancer immunotherapy. Dendritic cells (DCs) are critical players in producing an antitumor immune response and have been employed as a cellular cancer vaccine in a number of clinical trials (6,7). Using DCs provides a unique immune response against tumor-associated antigens (TAAgs); therefore, DC-based vaccines are capable of regulating and maintaining T cell functions that generate an effective cellular immune response (8,9).
The present study was designed to construct a potential breast cancer vaccine in which DCs were primed by intact viable cancer cells. This strategy is advantageous in that the cancer cells provide a full complement of TAAgs, including major histocompatibility complex (MHC) class I and class II-restricted epitopes, and can provoke an immune response against numerous unknown tumor antigens and may therefore overcome the hazards of immunological escape by antigen loss variants.
Patient selection
The current study was conducted using 30 patients with breast cancer lesions and 15 age-matched healthy controls. The patients presented to the Surgical Oncology Unit of the National Cancer Institute (NCI), Cairo University (Cairo, Egypt), between March 2014 and June 2016. The ethics committee of the NCI of Egypt approved the study, and written informed consent was obtained from patients prior to enrollment.
MCF-7 breast cancer cell line
MCF-7 cells were obtained frozen in liquid nitrogen (−180°C) from the American Type Culture Collection (Manassas, VA, USA). The tumor cell line was maintained via serial sub-culturing in RPMI-1640 medium supplemented with 10% heat-inactivated fetal bovine serum (FBS), 100 U/ml penicillin and 100 µg/ml streptomycin (Biowest LLC, Kansas City, MO, USA) in a humidified incubator at 37°C with 5% CO2, at the Cancer Biology Lab of the NCI.
Isolation of mononuclear cells and production of DCs and lymphocytes
Mononuclear cells were isolated from peripheral blood by Ficoll-Hypaque density gradient centrifugation (Biowest LLC, Riverside, MO, USA). Centrifuging was performed at 60–100 × g for 30–40 min at 18–20°C (10,11). The mononuclear cells were cultured in RPMI-1640 medium supplemented with 10% heat-inactivated FBS, 100 U/ml penicillin and 100 µg/ml streptomycin for 24 h in a humidified incubator at 37°C with 5% CO2. The non-adherent cells (lymphocytes) were removed by gently washing with pre-warmed (37°C) tissue culture medium containing recombinant human interleukin (IL)-2 (2 ng/ml). The adherent cells (monocytes) were cultured in RPMI-1640 medium containing recombinant human cytokines, granulocyte monocyte-colony stimulating factor (GM-CSF) and IL-4 (700 and 500 IU/ml, respectively; Koma Biotech Inc., Seoul, South Korea), thereby producing immature DCs.
Immature DC (IDC) loading with MCF-7 breast cancer cells
On day 5 of culture, IDCs were co-cultured with MCF-7 breast cancer cells for 24 h at a ratio of 10:1 in RPMI-1640 medium with 10% FBS, 100 U/ml penicillin and 100 µg/ml streptomycin in a humidified incubator at 37°C with 5% CO2 to generate mature DCs (MDCs).
T cell priming by autologous MDCs
Lymphocytes were counted and added to the flask of co cultured MDCs and MCF-7 cell line at ratio of (lymphocytes: DCs; 10:1) for 2 days. The count was estimated upon characterization of DCs using a flow cytometer and confirmed using a hemocytometer. Note that mature DCs are not adherent to the flask compared with the tumor cell line. A number of time periods were investigated (not shown) and the time period of least duration with favorable results [increased expression of cluster of differentiation (CD)4+, CD8+ and decreased expression of CD4+CD25+brightFoxp3+] was selected, as the present study aimed to make a simple immunotherapeutic model in the shortest time possible.
Cytokine detection via ELISA
Media was obtained prior to and following co-culture of DCs and T cells for estimation of interferon-γ (IFN-γ), IL-12 (cat nos. K0331121 and K0331124, respectively; Koma Biotech Inc.) and Foxp3 (cat no. 201702; Glory Science Co., Ltd, Shanghai, China) via an ELISA, according to the manufacturer's protocol. Cytokine release was reported as the mean ± standard error of the mean (SEM).
Flow cytometric analysis
DC phenotypes were determined using monoclonal anti-human CD86-FITC, CD83-PE and MHC-II-APC antibodies (cat nos. FAB141F, FAB1774P and IC7169A, respectively; R&D System, Inc., Minneapolis, MN, USA) prior to and following loading with tumor cells. T-cell immunophenotype characterization was conducted via CD3-APC, CD4-FITC, CD8-PE conjugate (cat no. 15080668, eBioscience, Inc.), CD25-ECD and Foxp3 PE-CY7 (cat nos. 4238109 and 560046, respectively; Beckman Coulter, Inc., USA). For surface markers, samples were stained according to the manufacturer's protocol. Cells were lysed and washed twice with PBS, centrifuged at 1800 rpm for 3 min and incubated for 30 min in darkness at room temperature. Foxp3 was prepared using an IntaPrep permeabilization kit (Beckman Coulter, Inc., Brea, CA, USA). Intracellular staining was performed using IntaPrep permeabilization reagent, by which cells were fixed with reagent 1 (fixation reagent using formaldehyde). Following washing, cells were permeabilized using reagent 2 (using Saponine for permeability). Buffer was supplied from a Foxp3/Transcription Factor Staining Buffer Set (00–5523; eBioscience; Thermo Fisher Scientific. Inc., Waltham, MA, USA). Samples were analyzed using a flow cytometer (NAVIOS; Beckman Coulter, Inc., Figs. 1 and 2).
FOXP3 expression in normal control. The gating strategy based on gating on lymphoid region then CD4+ population then CD4+CD25+ population and finally detecting the CD4+ FOXP3+ population. FOXP3+, forkhead box protein 3.
Measurement of CD4+CD8+, CD4+CD25+, and CD4+CD25+FOXP3+ before and after activation in breast cancer cases. (A) CD4 expression and CD8 in the first histogram. Second histogram CD4+CD25+ gated on CD4+ population. Third histogram is CD4+ against isotype control. The last histogram is estimating CD4+FOXP3+ gated on CD4+CD25+, before activation with D.C based vaccine. (B) CD4+ and CD8+ expression were increased. CD4+CD25+ as well as CD4+CD25+FOXP3+ were much reduced after activation with D.C based vaccine. FOXP3+, forkhead box protein 3.
Detection of cytotoxicity produced by activated CTLs
Cytotoxicity was assessed by measuring LDH release from the MCF-7 breast cancer cell line prior to and following co culture with CTL for 2 days, using an ELISA (cat no. SEB864Hu, Cloud-Clone Corp., Katy, TX, USA) according to the manufacturer's protocol. T cells were added to the population of tumor cells and DCs in the same flask to ensure that antigen presentation, T cell activation and exposure to tumor cells occurred simultaneously in order to mimic what occurs in the tumor microenvironment, and allow interactions with different cytokines. This was a preliminary step for immunotherapy preparation.
Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay of FOXP3 gene expression in CTLs
RNA was purified from samples using the SV Total RNA Isolation System (Promega Corporation, Madison, WI, USA), and cDNA was produced using a High-Capacity cDNA Reverse Transcription kit (Applied Biosystems; Thermo Fisher Scientific, Inc.), conducted according to the manufacturer's protocols. Two primer sets were designed to eliminate the possibility of primer dimer formation and nonspecific annealing using Primer3 (version 4.0; http://bioinfo.ut.ee/primer3-0.4.0/) and oligoanalyzer 3.1 (https://eu.idtdna.com/calc/analyzer) software: One for the gene of interest, FOXP3 (forward, 5′-ACTGACCAAGGCTTCATCTGTG-3′; and reverse, 5′-GGAACTCTGGGAATGTGCTGT-3′); and one for the housekeeping gene β-actin (forward, 5′-ATGATATCGCCGCGCTCA-3′; and reverse, 5′-CGCTCGGTGAGGATCTTCA-3′). Expression levels of β-actin were measured as a reference for the target gene expression. Each PCR was performed in a final volume of 10 µl, including 1 µg of the cDNA product, 1 µl (50 nM) of each primer and 2X reaction mixtures containing Fast Start DNA polymerase, reaction buffer, dNTPs, and SYBR-Green (Applied Biosystems; Thermo Fisher Scientific, Inc.) according to the manufacturer's protocol (12). The thermal cycling conditions comprised a temperature profile of 95°C for 10 min for denaturation, followed by 40 cycles (95°C for 15 sec and 60°C for 60 min) in a ViiA™ 7 Real-Time PCR System (Applied Biosystems; Thermo Fisher Scientific, Inc.). The RT-qPCR amplification products were analyzed via melting curve analysis.
The relative expression of gene transcripts was calculated according to the ΔCq and 2−ΔΔCq formulas according to Schmittgen and Livak (13). Finally, the ratios of target to reference gene were determined with the Pfaffl method (14).
Statistical analysis was conducted using SPSS version 24 (IBM Corp., Armonk, NY, USA). Data are expressed as the mean ± SEM. Comparison between groups was performed using paired Student's t-test for comparison between variables prior to and following activation. Pearson correlation analysis was applied for quantitative variables. P<0.05 was considered to indicate a statistically significant difference.
DC activation and maturation ex vivo by exposure to tumor antigens of viable breast cancer cells
The present study was conducted on 30 patients with breast cancer and 15 control healthy females with mean ages of 53.9±10.9 and 50±9.4 years, respectively (Table I). CD83 and CD86 were significantly increased on DCs isolated from breast cancer patients and healthy controls (P<0.001) following loading with viable MCF breast cancer cells for 24 h (Fig. 3).
Expression of CD83 and CD86, and their co-expression in DCs from (A) breast cancer patients and (B) healthy controls following priming of DCs with MCF-7 breast cancer cells ex vivo. Data are presented as the mean ± standard error of the mean. Statistical comparisons were performed using Student's t-tests. *P<0.05 and **P<0.001 vs. before activation. DC, dendritic cell.
Table I.
Clinicopathological characteristics of 30 patients with breast cancer.
Invasive ductal carcinoma 23
Invasive lobular carcinoma 4
Tubular carcinoma 2
Papillary carcinoma 1
II 20
IV 4
Axillary lymphadenopathy
Distant metastasis
III 16
Activation of CTLs
The activation of T lymphocytes was confirmed by the upregulation of CD4, CD8 and CD3, detected by flow cytometric analysis. Significant increases in the levels of CD4+ T-helper (Th) cells and CD8+ CTLs were observed (P<0.001; Fig. 4A and B). However, there was a significant decrease in the CD4+CD25+brightFoxp3+ regulatory T cell (Treg) subpopulation (P<0.001) isolated from breast cancer patients and healthy controls following activation with MDCs previously loaded with whole viable MCF-7 cells (Fig. 4C and D).
Expression levels of T-cell markers following activation with mature dendritic cells. CD4 and CD8 expression on T cells isolated from (A) breast cancer patients and (B) healthy controls. CD4+CD25+ and CD4+CD25+Foxp3+ expression on Tregs isolated from (C) breast cancer patients and (D) healthy controls. Data are presented as the mean ± standard error of the mean. Statistical comparisons were performed using Student's t-tests. *P<0.05 and **P<0.001 vs. before activation. Tregs, regulatory T cells.
Cytokine detection by ELISA
The effect of priming DCs with viable MCF-7 breast cancer cells resulted in a significant increase in IL-12 secretion in the media of DCs from breast cancer patients and healthy controls (P<0.001). Furthermore, activation of Th cells by the vaccine resulted in a significant elevation in the IFN-γ level in the media of T cells isolated from breast cancer patients and healthy controls (P=0.001; Fig. 5A and B). This was confirmed by the significant association between the IL-12 and IFN-γ levels (P<0.05; r=0.399). IL-12 also positively correlated with LDH (P<0.05; r=0.418). There was a significant decrease in Foxp3 released in the media of T cells isolated from breast cancer patients and healthy controls (P<0.001) following activation with MDCs previously loaded with whole viable cancer cells (Fig. 5C).
IFN-γ and IL-12 levels prior to and following activation with DCs isolated from (A) breast cancer patients and (B) healthy controls. (C) Level of Foxp3 released into the media prior to and following activation with DCs in breast cancer patients and healthy controls. (D) LDH released in the media of MCF-7 cells prior to and following exposure to activated lymphocytes from breast cancer patients and healthy controls. Data are presented as the mean ± standard error of the mean. Statistical comparisons were performed using Student's t-tests. **P<0.001 vs. before activation. IFN-γ interferon γ; IL-12, interleukin 12; DC, dendritic cell; Foxp3, forkhead box P3; LDH, lactate dehydrogenase.
Detection of CTL cytotoxicity
There was a significant elevation in LDH release in the media of MCF-7 cells following mixing with CTLs induced by the whole viable cancer cell-primed DCs (P<0.001; Fig. 5D).
RT-qPCR for Foxp3 gene expression
There was a significant decrease in FOXP3 gene expression in CTLs induced by the DC-based vaccine (P<0.001). The fold change was 8.26±0.77 prior to activation, and 0.92±0.09 following activation (Fig. 6). In breast cancer patients, there was a significant inverse correlation between Foxp3 gene expression and the level of CD4+ Th cells (P<0.05; r=−0.389).
FOXP3 gene expression in cytotoxic T lymphocytes following activation with mature dendritic cells from breast cancer patients. Data are presented as the mean ± standard error of the mean regarding fold change in patients in relation to control. Statistical comparisons were performed using a Student's t-test. **P<0.001 vs. before activation. FOXP3, forkhead box P3.
A number of studies have been conducted to enhance the antitumor immune response in breast cancer through priming DCs; however, selecting and optimizing the antigen-loading strategy has been demonstrated to be a challenging undertaking (6,8,15). The most common method is by using freeze-thawed ordinary lysates that are obtained by subjecting cancer cells to several freeze and thaw cycles using liquid nitrogen and water baths (16,17). However, DCs loaded with such lysates have not provided complete protection against tumor responses in differential animal models (16,18,19). Furthermore, in clinical trials, numerous studies have demonstrated that freeze-thawed lysates are ineffective for therapy as they suppress DC maturation and function (17,20,21).
The present study attempted to optimize tumor antigen loading with DCs by a novel strategy. This was obtained by subjecting DCs isolated from breast cancer patients, or healthy controls as a comparison, to intact viable MCF-7 cells in complete conditioned RPMI-1640 medium. The activation of DCs was demonstrated by significantly increased levels of the stimulatory molecule CD86, maturation molecule CD83 and MHC-II. The elevation of such molecules may enhance the capacity of DCs to prime T cell responses. By contrast, other studies have used DCs loaded with cell culture supernatants that may not have contained sufficient or adequate antigens secreted in the media (22). Additionally, a previous study demonstrated reduced levels of CD80, CD86 and CD40 in DCs loaded with irradiated tumor cells (23).
Another important feature of mature active DCs is the production of IL-12. In the present study, there was a significant increase in its secretion, from 160.03±10.27 pg/ml prior to activation to 254.60±12.67 pg/ml following activation of DCs with viable tumor antigens. IL-12 has a crucial importance in the differentiation of naive T cells into Th cells and subsequently in initiating an active specific immune response through the induction of IFN-γ and tumor necrosis factor-α from T cells and natural killer cells, as demonstrated by Vieira et al (24).
The results of the present study revealed that the interaction of viable cancer cells and DCs resulted in stimulation of CD4+ Th cells and CD8+ CTLs against a wide range of tumor antigens. This was confirmed by the increased expression of CD4+, CD8+ and CD3+ cells by flow cytometry, as well the increased secretion of IFN-γ by reactive tumor antigen-specific CD4+ Th cells. An explanation for these findings is that these cells were capable of inducing IFN-γ and TNF-α, and serve a role in priming tumor-specific CTLs through the release of IL-2 (25). These results suggested that DC priming by whole, intact tumor cells induced a differential MHC class I and II cross-presentation of tumor antigen to T cells, as reported by Kini Bailur et al (26), and therefore induced a potent antitumor immune response.
Furthermore, this vaccine type resulted in a significant decrease in an important subset of T cells, CD4+CD25+Foxp3+ Tregs, which are increased in the blood and tumor microenvironment of patients with breast cancer compared with healthy subjects (27,28) and its level is correlated with advanced clinical stages (29). Previous studies have emphasized the role of Tregs in the suppression of antitumor immune responses, as they are considered to exhibit critical functions in the progression and modulation of immunological escape mechanisms in malignancies. These cells express FOXP3 and CTL-associated protein-4 (CTLA-4), as negative regulatory molecules of active immune cells, and are increased in breast cancer patients (30,31). Increased expression of Foxp3 and subsequently Tregs are considered obstacles that may hinder the desired response of potential immune therapeutic strategies (30–32). Therefore, in the present study the level of Foxp3 protein secreted in the media of cultured T lymphocytes from breast cancer patients was assessed, which demonstrated a significant decrease in Foxp3 following the subjection of T cells to tumor cell-primed DCs (P<0.001). This was confirmed by a significant downregulation of Foxp3 gene expression in CTLs as detected by RT-qPCR. Furthermore a significant upregulation of Foxp3 gene expression (~12-fold higher) was observed in peripheral blood of patients compared with normal healthy controls, which was consistent with the results of Hamidinia et al (33). This was also confirmed by the inverse correlation between FOXP3 gene expression and CD4+ Th cell levels identified in the peripheral blood of the patients enrolled in the present study. These findings suggested that the immune system was suppressed in breast cancer patients, which may be due to an augmentation in the Treg population and suppression of effector Th cells.
An alternative way to assess the efficacy of the viable cancer cell-DC based vaccine was through the detection of cytotoxicity exerted by activated CTLs on MCF-7 cells through the measurement of LDH release. The results demonstrated a significant increase in LDH level, indicting a highly active and potent immune response against these cancer cells. As described by Faloppi et al (34), LDH is typically released from necrotic cells. Therefore, the higher the degree of necrosis, which is related to tumor volume, the higher the level of LDH. It is important to clarify that a significant positive correlation was identified between IL-12 produced by this type of viable cancer cell-based vaccine and the increased level of IFN-γ, also, IL-12 was positively correlated with increased cytotoxicity and necrosis of tumor cells via the increased level of LDH. Therefore, the current study has identified an avenue for further studying the development of novel effective immunotherapy for patients suffering from breast cancer using DCs.
In summary, the current study demonstrated that a viable cancer cells are an effective source of TAAs for pulsing DCs, which may be utilized in the immunotherapeutic treatment of breast cancer. The matured DCs induced expansion of TAA-specific T cells, namely CTLs and Th cells. A strong cytokine response was provoked through increased IFN-γ and IL-12 levels. Additionally, an augmentation of the immune response was indicated by decreased Tregs and Foxp3 expression, and an elevation of CTL activity, as indicated by an increase in LDH release.
The present study was supported by the National Cancer Institute, Cairo University (Cairo, Egypt).
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Faloppi L, Bianconi M, Memeo R, Gardini Casadei A, Giampieri R, Bittoni A, Andrikou K, Del Prete M, Cascinu S and Scartozzi M: Lactate dehydrogenase in hepatocellular carcinoma: Something old, something new. Biomed Res Int. 2016:71962802016. View Article : Google Scholar : PubMed/NCBI
Abdellateif, M.S., Shaarawy, S.M., Kandeel, E.Z., El‑Habashy, A.H., Salem, M.L., & El‑Houseini, M.E. (2018). A novel potential effective strategy for enhancing the antitumor immune response in breast cancer patients using a viable cancer cell‑dendritic cell‑based vaccine. Oncology Letters, 16, 529-535. https://doi.org/10.3892/ol.2018.8631
Abdellateif, M. S., Shaarawy, S. M., Kandeel, E. Z., El‑Habashy, A. H., Salem, M. L., El‑Houseini, M. E."A novel potential effective strategy for enhancing the antitumor immune response in breast cancer patients using a viable cancer cell‑dendritic cell‑based vaccine". Oncology Letters 16.1 (2018): 529-535.
Abdellateif, M. S., Shaarawy, S. M., Kandeel, E. Z., El‑Habashy, A. H., Salem, M. L., El‑Houseini, M. E."A novel potential effective strategy for enhancing the antitumor immune response in breast cancer patients using a viable cancer cell‑dendritic cell‑based vaccine". Oncology Letters 16, no. 1 (2018): 529-535. https://doi.org/10.3892/ol.2018.8631

redpajama_set_name: RedPajamaCommonCrawl


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Soyuz MS-11 Spacecraft Safely Returns back to Earth Expedition 59 Space Crew
Three Optolink's TRS-500 fiber-optic gyroscopes, installed into control system of Descent Module of the latest Soyuz modification, Soyuz MS-11 spacecraft, successfully executed their mission during landing. The Russian Soyuz MS-11 safely returned with Expedition 59 crew members, Soyuz Commander Oleg Kononenko of Roscosmos, NASA astronaut Anne McClain, and Flight Engineer David Saint-Jacques of the Canadian Space Agency. The landing module safely landed on-target about 148 kilometers south-east from the town of Dzhezkazgan in the Kazakhstan on 25 June 2019, at 02:47 UTC (08:47 local time). The crew completed a 204-day mission spanning 3,264 orbits of the Earth and a journey of 86.4 million miles. Over the past six months, the Expedition 59 crew members helped conduct hundreds of science experiments and oversaw the arrival and departure of several resupply ships. They were also in place to receive the first U.S. commercial crew spacecraft, SpaceX's Crew Dragon. Expedition 59 was Kononenko's fourth stay on the International Space Station. He has now logged more than 737 days off Earth, ranking him sixth in the world for the most time accumulated in space.


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November 29, 2021 November 29, 2021 kristel
International day of solidarity with the Palestinian people
Every year on the 29th of November it is the International Day of Solidarity with the Palestinian people. This was decided in the United Nations in 1977 when the General Assembly adopted resolution 32/40B. It was not a coincidence that they chose this date. It is the same date that the United Nations Partition Plan, resolution 181, was adopted exactly 30 years before, in 1947.
The United Nations Partition Plan of 29 November 1947
The partition of Palestine by the UN gave the Zionist movement the push they had been waiting for to establish their Jewish homeland in Palestine. This happened with a lot of force and violence. Most of the Palestinian villages, towns and cities were partially or completely depopulated and destroyed. Until today families from these towns and cities can be found living in refugee camps in the Westbank, Gaza and neighboring countries. The fourth generation is now brought up under very difficult circumstances.
The ongoing colonization of Palestine
In the meantime the State of Israel was created in 1948 and in 1967 this new country took its chance and military occupied the Gazastrip, the Westbank, Sinai and Golan Heights. It started moving its own population into the territory it occupied. They moved mainly into settlements built on Palestinian agricultural land, but in Jerusalem and Hebron they also moved inside the city.
What can I do in solidarity with the Palestinian people?
For this podcast episode I asked several Palestinian friends to send me an answer to the question: What do you think that people can do in solidarity with the Palestinian people?
You can hear Hassan Muamer from Battir, who is active in alternative and eco-tourism. Majdi from Handmade Palestine talks about the importance of supporting local artisans and the local economy. Fayrouz Sharqawi from Grassroots Al Quds emphasizes the importance of holding governments and corporations responsible for their support to Israel and the profits they make despite the gross violations of human rights by Israel.
Anwaar, who is from Hebron and lives in Shuhada street, the infamous street that is closed off by military checkpoints, tells us a bit about life in the old city of Hebron. She says she really appreciates people coming to witness and to give protective presence. The last one is Jack Munayyer who works for the EAPPI, the Ecumenical Accompaniment Program in Palestine and Israel. Jack points out that coming to Palestine as a tourist to see the situation of Palestinians, also comes with a responsibility to act up. If the visit is not followed by action, it is useless solidarity. The situation is urgent and the need for change is very real. Everyone has to consider their own circumstances, government, stake-holders and capacity to decide what they can do in solidarity with the Palestinian struggle for justice and peace.
Educate yourself on Palestine
I hope that this will inspire you to look for initiatives, campaigns, projects, films, books, websites and other ways to educate yourselves more and to join the existing efforts. We don't all have to start a new initiative. There are many campaigns that are running and that need people to participate, to support, to volunteer. You can make a difference by dedicating a bit of time. There are also organizations that plant trees, just like what we heard in previous episodes, the people of Handmade Palestine at their arboretum. I will add a few important links from where you can start.
Www.grassrootsalquds.net
www.handmadepalestine.org
https://eappi.org
https://bdsmovement.net
Podcast 29 November, international, israel, palestine, palestinian, partition plan, resolution, solidarity, un, united nations
Tel el Qadi / Tel Dan archaeological site


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Nintend'oh!
by Oli
Let me start by saying one thing: I was, and to some degree still am, a huge Nintendo fan. I grew up surrounded by a Super Nintendo, Game Boy, Super Game Boy, N64, Gamecube and even a DS and a Wii. I thrived on the adventures of Mario, Donkey Kong, Diddy Kong, Kirby, Link, Samus, Yoshi and the rest of the colourful cast of characters under the huge red umbrella marked N. But… my love affair would always end the same. My SNES was accompanied by a Mega Drive, my N64 became a Playstation, Gamecube a Playstation 2 and my DS and Wii combined to finance an Xbox 360.
Eventually, while I enjoyed the escapades that Nintendo offered me, like an unhappy housewife, I always looked at the cool games the other consoles were housing and found myself wishing for those. And like that unhappy housewife, I would often up sticks and jump into the flash sports car offered by Sony and Microsoft and drive off, leaving my well-meaning, but ultimately unfulfilling, fat Italian husband behind.
Therefore, it is with no surprise (but considerable sadness) that Nintendo announced recent losses that were triple those which had been forecast. Now, while most gamers are not interested in cold, hard numbers, these particular ones are staggering: instead of a forecast loss of ¥20 billion for the full year ending March, they are looking at a staggering ¥65 billion loss. While Nintendo President Saturo Iwata is going full damage control, stating that next year Nintendo will bounce back bigger than ever with the launch of Wii U, these are still bad numbers.
So the question gamers of my generation have to ask is: "what went wrong?" What happened to the innovative, industry-defining and ultimately, fun video games company we all grew up with? Unfortunately the simple answer is in those adjectives: misjudged innovation, stagnant ideas and a lack of what fun is. Let me start with the first one. At first I wanted to say "lack of innovation", but knew many Nintendo loyalists would shout: "Oli, you crazed fool! Nintendo are the front-runners of innovation! Look at the 3DS! The Wii! This is technology for the future!" Well, yes. Yes they are, hence why I changed it to "misjudged innovation". You see, while the Wii and 3DS did bring new technology into the world of video games, they weren't for the best. I'm not talking Virtual Boy levels here, but it's depressingly close.
Say cheese. Lots of cheese...
Starting with the Wii, the cold hard truth is if you ask most 'hardcore' gamers (and even those on the cusp between that and casual), they will say that they simply don't want motion control. The argument is that it doesn't work, is implemented terribly (or annoyingly) and, most of all, it doesn't replace the feeling of actually holding a controller and pressing buttons. One only has to look at the backlash Microsoft has had with Kinect to see how your average gamer feels about 'being the controller'.
Naturally, you could argue that the Wii appeals to a different demographic than the Xbox 360 does, and that is true. However, that market is the casual gamer market; casual gamers who, while profitable at first (combined with the curious average gamer), will slowly taper off due to lack of interest. I mean, if you look at the games that fully implement motion control, you find yourself looking at the likes of Wii Fit and party games such as Wii Sports. Popular platformers such as the Mario Galaxy series and even, err, New Super Mario Bros (there's my second point appearing early…) rely less on shaking a controller and more on holding the Wiimote like a classic controller. It seems even Nintendo are realising that the motion control world isn't as fine-tuned as it needs to be to hold an audience yet.
Which brings me to the 3DS. When it was announced, you simply had to be impressed. After all, this was 3D gaming without the need for glasses. With 3D hitting other areas of the entertainment industry, this was the perfect time to jump on the bandwagon and start selling the stunning visual nature of 3D to the gaming masses. However, this came with one small problem in that not everyone liked 3D. The larger problem came with this: how do you show off 3D in a largely 2D showcasing world (i.e. TV advertising)? While an outstanding innovation, the 3DS was simply a victim of its own gimmick. The only way you could really see the effects was if you had one in your hand, and with early prices in the £200.00 range, it was an expensive gamble to make.
On top of that came another problem in this troubled hand-held's life in that the 3D was very unreliable, or was simply bad for you. From personal experience, I can say that when I first tried the 3DS after borrowing one from a friend, I was very impressed with the 3D, but after a few minutes I started to get a headache, my eyes were shifting in and out of focus and I found myself not so much playing the game on screen as trying to stop myself having a seizure. Other gamers I know have said similar things: that while the 3D is pretty, it plays hell with your vision, and some of those gamers have just turned the 3D off.
The one character we just don't see enough of. Ahem.
So while the innovation has been "meh" at best, my other two points – stagnant ideas and a lack of fun – probably best highlight my problem with Nintendo. As I've mentioned, Nintendo's cast of characters endeared me to their consoles, but as I grew older I started to see the cracks behind the bright wallpaper. Nintendo now fully relies on these characters to sell themselves, and really one character in particular – Mario. Thinking of all the recent games Nintendo have launched, all I can think of are the ones with Mario in the title: Super Mario 3D Land, Mario Kart, Mario Party, Super Mario Galaxy, New Super Mario Bros Wii, Mario and Sonic at the Whatever Olympics Are This Year.
Now, while gaming has fallen into the pit of franchising in recent years (CoD, Halo, Gears of War, Uncharted, Battlefield…), Nintendo are leaning heavily on one small, fat, Italian plumber. Unfortunately this is what made me move away from Nintendo all those years ago – a lack of variety. Again, the argument could be made that there is variety in the Zelda games, but they also suffer the same lack of real innovation in gameplay that Mario does. While there is nothing wrong with an 'ain't broke so don't fix it' mentality, after a while you end up with a feeling that you simply don't want from games, namely boredom.
So what now for Nintendo? Where does the Big Red N go from here? Well, the Wii U will be coming out soon, also with its own innovation, this time in terms of a screen in the controller. In addition to this, a wider range of games have been announced, including some Triple A titles such as Arkham City. But is this too little, too late? Has Nintendo finally seen itself as the geeky kid at the party filled with mature, cool kids whom all the girls (in the case of this metaphor, gamers – sorry male gamers) want to hang around and be with? If it has, the real question is: does it finally bite the bullet and try to hang with the cool kids, or does it stand up for their ideals, ride the rough times, and maintain itself as an individual? As an old fan, I hope they stay with the latter, but I fear in today's age of HD graphics and BIG gaming, they may find themselves on the road to a fate worse than Sega.
How To Avoid Multiplayer
Day 1: Kombating Fatigue with Bubba
Halo 4 - E3 Preview
Auto Cannibalism Is Not The Answer
Bad Games Happen
Best of 2015: End of the World
Last five articles by Oli
Welcome to the Multi-Shooter-Verse
In Defense of Brink
Nintend'oh!
Tags: 3DS, 3DS headaches, childhood gaming, eat that mushroom, Mario games, Nintendo, Nintendo and innovation, Nintendoh!, Ninty, Oh fuck no not another Mario game, overused gaming characters, Wii takes the piss, Yoshi, Zelda
tanto says:
The 3ds is number 1 worldwide dude.
Nobody moved more hardware or software than nintendo did in 2011.
The 3ds is kickign everyones ass
From a slightly less fanboyish perspective, I still own the complete set from the SNES through to the Wii. The latter console was where the rot set in though. For every Mario Galaxy there's an inexplicably popular load of shit like Carnival Games. Come the 3DS launch I've been ambivalent whereas before I'd have got it one day one. Cool though Wii-U is from a tech perspective, I doubt I'll ever get one unless Nintendo seriously buck their ideas up.
Although from my point of view, the game was up for Nintendo (and Sony to a lesser extent) when that first ever achievement popped in March 2006.
Yourmom says:
Nothing happened to Nintendo. They have remained the same successful, fun, innovative company they have always been. It's Sony and Microsoft that have convinced the idiot-masses that motion control "didn't work," and that developers needed to shove games full of HD FMVs, and waste more money on advertising than on actually making better games, all the while half-assedly copying Nintendo's every move when it proved to be successful.
I had every Nintendo console up to and including the Wii. I was so horribly disappointed that I made the switch to Xbox and have never looked back. I remember when I first booted up the Wii and on seeing the horribly blurry graphics saying "what's up with the screen?". After a little research I found out that it wasn't my TV but that the console wasn't designed to be HD compatible or whatever. At a time when all televisions were switching over to flat-screen and digital and all that, it was just unacceptable. Plus being forced to play with motion control when I just want to crash out on the sofa after a hard day at work is a big NO.
Well thought and argued article, especially as a first one on the site
As a self-proclaimed Nintendo fanboy, I have to admit there are some disagreements but not to the extent other people have expressed. Granted, the 3DS suffers from bad press more than anything (everyone saying it's doing terribly when it's not, etc) and I think the last new IP they made was Nintendogs, and I'm still neutral on the Wii U (apart from the fact it's an awful name), but here's the thing:
Most of my favourite games this generation, and even ever have been on the Wii.
Yeah, Mario is overused to the point of self-parody, but it doesn't matter to me when the games are so good. And while motion control isn't always for the hardcore gamer, I appreciate it more as an example of what can be made with the technology rather than how successful they were making everyone use controls.
Yeah, they're retreading old ground and they're really out of touch with everyone and I agree with most of your points, as long as they keep making games I love, I'll continue supporting them.
C&C: Red Alert 3
Fighting Russian Bears
Gemma Atkinson's short skirt
Oh no, there's Japan!


Take advantage of the fresh air while getting a little exercise and making new friends. There is a play area for kiddies to swing, slide, and play, and a large sports field perfect for tossing a frisbee or playing catch. In addition, there is a full size volleyball court, plus two horseshoe pits for your enjoyment. Or just relax and enjoy the peace and tranquility of the summer sun, or the glow of an evening campfire with your family and friends.


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DOLL AND ME - style edit
Aiming to make all women feel their most fashionable and confident selves, the brand Doll and Me provides clothing to do just that.
All items are handpicked by Doll and Me, resulting in a collection of high quality and unique clothing! Whilst, researching into trends and developing their own fashion forward creations made and printed in the UK which are accessible to all women at an affordable price. The need for long term is a growing trend which is why Doll and Me believes in supplying style staples that can be worn in a variety of ways throughout the seasons. Below is a number of Doll and Me wardrobe must haves and how they can be styled.
Feather Too Much T-shirt £24.99
Made from 100% Organic Combed Cotton the Feather Too Much T-shirts are handmade in the UK. The feathers are detachable to allow customers to mix and match with different colours. This T-shirt is so easy to style dressed down with denim shorts and trainers or dressed up with ripped straight leg jeans with heels for a more casual dressy look.
Luxe Living Tote £14.99
Sustainability is a huge trend right now, but it can be hard to find pieces that look good whilst providing the sustainable need. The Doll and Me Luxe Living Tote works as an everyday bag made to be styled causally and for the customers day to day needs. The Luxe Living Tote can be styled in so many ways due to its colour palette.
Custom Hoody Style One £29.99
The current Doll and Me best seller! The Custom Hoody Style One plays into the the custom craft trend circling on social media currently. This piece revamps the basic black hoodie and adds a chicness to it making your basic never feel like a basic again. Style with denim shorts, blazer and Givenchy Shark boots for a dressed up look or wear casually with your favourite joggers and trainers.
Supermodel Personalised Tee £24.99
One of the first items from the SS20 collection was the Supermodel Personalised Tee which is made from the same organic material of the Feather Too Much Tshirts. Doll and Me have designed the tees in house and have them printed for the consumer locally in the UK. All tshirts can be personalised with a doll of the customer's choice. Style the Supermodel tee with nude leather shorts, Bottega Style mules, blazer and clutch bag for a brunch with friends or keep it dressed down with cycling shorts and trainers for your morning coffee run.
In A Ruche Top £14.99
The In A Ruche Top comes in 3 different colours: black, nude and white. Each bringing endless outfit possibilities. The drawstring ruche detailing allows the customer to decide on their perfect cropped length depending on how they'd like to style. Style with leather trousers and trainers for a textured look but if you prefer a layered look style with a shirt underneath.
Power Moves Shoulder Pad Multiway Dress £19.99
Although Doll and Me try to stay away from fast fashion trends the shoulder pad trend was one that could not be resisted especially as the Power Moves dress can be styled in 3 different ways making it a long lasting piece in the customers wardrobe. Our favourite is styled with a knot at the bottom, turning it into the perfect bodycon dress. For a casual look tie up at the back turning it into a tshirt or add a belt to create a looser silhouette.
To visit Doll and Me Click here Instagram - dollandmelondon
ICONIC MOVIES THAT REVOLUTIONIZED FILM & FASHION
These films have each had a major impact in fashion, life and culture.
Often I find myself looking for films that allow me to escape the reality of 2020.
These iconic films have resonated with me and I am confident that they will with you too. Many being very famous and already labelled 'iconic' for a reason, you have probably seen or heard of a few. If you haven't , I really urge you to.
Eccentric roles, fashion and art are all key factors in a these films. Many have inspired the way I think and dress today. Not being in order ,as I found that far too stressful to even contemplate here they are-
PULP FICTION (1994) see picture in right hand corner (Uma Thurman as Mia Wallace)
Crime film written and directed by Quentin Tarantino. Starring John Travolta, Samuel L. Jackson, Bruce Willis, Tim Roth, Ving Rhames, and Uma Thurman, it tells several stories of criminal Los Angeles.
KILL BILL V1 & V2 (2003 & 2004)
American martial arts film written and directed by Quentin Tarantino. Again starting Uma Thurman as the Bride, who swears revenge on a team of assassins (Lucy Liu, Michael Madsen, Daryl Hannah, and Vivica A. There are also rumors of Kill Bill 3 so give the first two films a watch.
Apart of netflix's Black Lives Matter section and in our current circumstances there is no better time to watch django unchained. A real eye opener and educational film into the lives of black people and how they were treated. The inhuman acts of violence made by white socialists and land owners is uncomfortable to watch but is executed well.
Directed by Quentin Tarantino. With Jamie Foxx, Christoph Waltz, Leonardo DiCaprio, Kerry Washington.
https://www.gofundme.com/f/ukblm-fund?utm_medium=referral&utm_source=unknown&utm_campaign=comms_h4hk+ukblm-fund
Please use this link to donate to black lives matter fund.
Another Quentin Tarantino films - Inglourious Basterds is a 2009 war film starring Brad Pitt, Christoph Waltz, Michael Fassbender, Eli Roth, Diane Kruger, Daniel Brühl, Til Schweiger and Mélanie Laurent. 't features multiple titled "chapters," many scenes of tense dialogue far more exciting than most movies action set pieces and of course plenty of gratuitous violence"
In Detroit, a lonely pop culture geek marries a call girl, steals cocaine from her pimp, and tries to sell it in Hollywood. Meanwhile, the owners of the cocaine, the Mob, track them down in an attempt to reclaim it.
AMERICAN PSYCHO (2000)
One of my favourites, we see Patrick Bateman slowly crumble. Seen as a popular socialite with the perfect life, the story is told in the first person by Patrick Bateman, a serial killer and Manhattan investment banker.
ISSUE ONE - THE 90's
see how you can recreate some of the most iconic looks from the 90's
The 90's has always been an era that has inspired me in many ways and not just in fashion. I really take an interest in the lifestyle of the 'celebrity' and how different life seemed even only 30 years ago. People seemed to party harder, rebel more and care less. I think this attitude ,which we should celebrate more, was used by designers to make some of the most iconic looks we are still captivated on today. The likes of Kate moss, Naomi Campbell, Cindy Crawford and Christy Turlington are just some of the names that spring to mind when thinking about these looks worn.
Here are some of my favourite looks and how we can recreate them today.


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Widely used in advertising LED displays, stadium perimeter LED screen, mobile led display for mobile media, shopping mall LED billboard for logo showing, bank & stock exchange LED message signs for rates showing, train & bus station, airport, telecommunication LED video wall system forinformation showing and instruction, Stage performances ect.
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● High intensity and can be adjusted, so can meet the request of the customers according the application environment.
● To pictures and character, have clear, exquisite and real display effect.
● Big viewing angle to 120-150 degree at horizontal line, 120-150 degree at vertical line, you can see at every angle at this range, no picture change, no color excursion.
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Thomas Jefferson was a Christian. Right? He peppered the Declaration of Independence with the use of the word "god" but does that make him a Christian? To find out if Jefferson believed in organized religion, it helps to read some of his writing on the subject.
Christians may think that just because he mentions "god", that makes him a Christian just like them. Jefferson absolutely believed in a god– but not the god of orthodox Christianity. He was a Deist (Nature's God), not a Christian (the trinitarian God of Abraham and Isaac).
Not surprisingly, Jefferson was regarded as an atheist by Christian ministers of his day. Yet, in the blind ignorance of our times, he is regarded, along with the other founders of the United States to be a Christian. That the United States was not originally a Christian Nation is beyond argument. One merely has to read the two major founding documents: The Declaration of Independence and the United States Constitution. Nothing about Christianity to be found anywhere in those pages.


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It costs an average of 2–3 percent to process a credit card payment. To compensate, many government and educational institutions pass on a flat-rate processing fee for card payments. But this approach is problematic because different card types have different processing costs.
Intelligent Rate for Government and Education, a solution from our partner CardX, solves this problem by pricing cards at their actual costs. As a customer types card info into the payment page, Intelligent Rate calculates the cost of the card and automatically prices the service fee in proportion to what the transaction will truly cost — allowing customers with low-cost cards to absorb a lower fee.
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Design with the user

Introduction

About me...

MSc in Industrial Design at Politecnico di Milano in 2006

Doctoral Candidate at Aalto University since 2011

Fab Academy 2012 diploma

Digital Fabrication & Open Design lecturer at Aalto University since 2012

FabLab Developer (Aalto FabLab, MUSE FabLab, Opendot), Open Design facilitator, ... since 2005

Director @ Make in Italy CDB Foundation

...

About me...

Source: http://www.openp2pdesign.org/speaker/

More about me...

Source: http://www.linkedin.com/in/massimomenichinelli

More about me...

Source: http://www.openp2pdesign.org

Course structure

13/11: Course introduction. Slides

13/11: User-centered Design, User-experience design, Co-Design: methodologies and tools / Lead users, Open Innovation and Open Source. Slides

20/11: Open Design+Metadesign: concept and development / Intellectual property and design: laws and the design process. +Install Software Bring your computer! Slides soon...

27/11: Digital Tools for Open projects: version control systems. Slides soon...

4/12: Practice: developing an Open project Slides soon...

Christmas Holiday: Online work @ GitHub

15/01: Practice: developing an Open project.

23/01: Practice: developing the physical Open project. @ FabLab

Where we will work together

Source: https://github.com/organizations/OpenDesign-SUPSI

Where to find the slides

Source: https://github.com/OpenDesign-SUPSI/Design-with-the-user_Slides

How to download the slides

Source: https://github.com/OpenDesign-SUPSI/Design-with-the-user_Slides/archive/master.zip

Contacts

						Massimo Menichinelli / info@openp2pdesign.org / @openp2pdesign

This work is licensed under a Creative Commons Attribution 3.0 Unported License.

Massimo Menichinelli 2014-2015

		openp2pdesign.org

redpajama_set_name: RedPajamaGithub


text:
Daisy Pettles
Shady Hoosier Detective Agency
Finalists Announced in Daisy Pettles Grants for Women Writers June 2020
February 25, 2020 By DaisyPettles Administrator
Bedford, Indiana (Lawrence County); Bloomington, Indiana (Monroe County); Southern Indiana arts and entertainment news
Daisy Pettles, Indiana author and philanthropist, is pleased to announce the grant finalists in the first annual Daisy Pettles Contest for Women Writers. The competition is open to women writers, aged forty or over, published or unpublished, working in all genres, except for poetry.
The competition, with a top cash prize of $1,000 and a free month-long residency in the Daisy Pettles House for Women Writers, was steep.
Applicants included a Fulbright Scholar, a Pushcart prize nominee, and several published novelists. Entrants came from diverse backgrounds and genres, ranging from political columnists to commercial romance authors.
A notable number of applicants had yet to be published, yet submitted works in progress that rivaled top prize-winning peers. Applications flowed in from across the United States, Iran, the United Kingdom, and Australia.
The judges have, in round one, narrowed the possible prize winners down to the top seven applicants.
Writing Contest for Women, Finalists – June 2020
Below is the official list of the June 2020 writing contest finalists, in alpha order.
Teri Carter – Lawrenceburg, Kentucky|
http://www.tericarter.net/home.html
Working on a Memoir … "The Real Mom," about the step-parenting experience.
Marie Drake – Golden, Colorado
Working on a Memoir … "Crack through My Heart," a memoir of growing up in the 60s and 70s with a drug-dealing, hippie mother, and a full-colonel CIA agent father.
Diane Hartman – Plainfield, Indiana
Working on a Memoir … "And All Shall Be Well: Driving the Backroads of Ireland and Finding Myself," a retired woman gathers her courage and goes in search of her ancestry.
Robin Israel – Scottsdale, Arizona
https://robinisrael.com/
Working on a Novel … "Leave the Frigging Marshmallows," a coming-of-age story about an adolescent girl growing up in a dysfunctional Jewish family in the 1980s.
Celena Janton – Vail, Arizona
Working on a Fantasy Romance Novel … "The Dreamers," based on a reimagined Greek myth.
Mehrnoosh Khorsand – United Kingdom
Working on a Novel … "How I Rescued My Daughter," about an Iranian girl forced into an unhappy arranged marriage for self-serving reasons by her father. Story based on author's experiences.
Robin Lovelace – Plainfield, Indiana
https://www.indianawriters.org/blogs/news/member-spotlight-robin-lee-lovelace
Working on a Novel … "The Hextens of Jackson County," a historical reimagining of a family of witches living in rural Indiana in the late 1940s
The top three women applicants, chosen from the above finalists, will be announced on March 15, 2020. They will receive the following support grants and recognition for their written works.
#1 – Grand Prize: Free Residency – Writer in Residence at the Daisy Pettles House in Bedford, Indiana, USA, a vintage 1920s bungalow, equipped with all the amentities a women writer might need to kick back and write her heart out, undisturbed, for a month … PLUS a $1,000 CASH grant.
#2 – 1st Runner-Up: $250 Cash Grant; PLUS Award Certificate as Finalist – Writer in Residence at the Daisy Pettles House for the year awarded; PLUS if for any reason the Grand Prize Winner is unable to attend the writing residency the residency immediately passes to the 1st Runner-Up.
#3 – 2nd Runner-Up: $100 Cash Award Grant; PLUS Award Certificate as Finalist – Writer in Residence at the Daisy Pettles House for the year awarded.
The final grants and free residency will be awarded based on writing talent along with a consideration of which women writers might benefit most from the awards given the details they chose to share with the judges in their application essays.
REMINDER to WOMEN WRITERS: the next women's writing competition, for a July 2020 residency and supporting grant, is still OPEN to applicants.
Submissions for the July prizes and residency close on April 15, 2020.
Older women writers (aged 40 or older) are invited to apply.
The Daisy Pettles Women's Writing Competition is sponsored by the Hoosier writer and philanthropist Daisy Pettles, in honor of her mother, June, an avid reader. June passed away in the spring of 2019, leaving her home in the care of her daughter, Daisy.
Daisy is working with a team of women writers, artists, and Indiana historical preservationists to convert the home, a vintage 1920s bungalow located in southern Indiana (Lawrence County, south of Monroe County, Bloomington), to a retreat and residency center for older women writers.
The goal of the Women's Writing House project is to discover, nurture, and reward diversity in women's voices and literature.
The Women's Writing House can be supported through donations at Go Fund Me.
Please follow & like Daisy :)
Visit Daisy's Author Pages
Copyright © 2021 · Daisy Pettles
View our Privacy Statement
Website Designed and Developed by It's Only Natural, LLC


text:
Hiro Nakamura är en rollfigur i TV-serien Heroes, spelad av Masi Oka. Hiro äger förmågan att förflytta sig i och manipulera tiden. Figuren har blivit en av de mest populära bland seriens anhängare.

Biografi
Hiro Nakamura blev förälskad i Charlie Andrews, en annan individ med övermänsklig förmåga, och försökte rädda henne från att bli dödad av Sylar genom att färdas tillbaka i tiden. Han lyckades inte med detta och insåg då att hans kraft var större än hans egna ambitioner. Han är en inbiten trekker, så hans förmåga att kunna förflytta sig lika snabbt som med en transportör i Star Trek är som en dröm för honom.

Tidsparadoxer och -ändringar
Tillsammans med mötet med en framtida Hiro har nutidens Hiro mött eller skapat flera tidsparadoxer eller förändringar av tidsflödet.
 Hiro reser med sin vän Ando till USA samtidigt som Ando fortfarande var i Japan när han tidigare gjorde ett rumtidshopp till New York fem veckor in i framtiden. På Andos direkta fråga om detta, så säger Hiro bara att de ändrar historien allt eftersom, vilket Ando accepterar.
 Hiro reste 6 månader tillbaka i tiden för att rädda Charlie.
 Väl tillbaka i tiden ändrade han historien igen genom att skapa en nära relation med Charlie, mest synligt genom att ett fotografi av henne vid hennes födelsedagsfirande nu också innehåller Hiro.
 Vid ett tillfälle ringde Hiro till sig själv i Japan. ** Charlie berättade för Hiro och Ando att hon hade fått en japansk parlör när hon fyllde år och senare visar det sig att det är Hiro som gav den till henne.
 Konstnären Isaac Mendez målar en gång en tavla som visar Hiro kämpandes med ett svärd mot ett förhistoriskt djur. Det har därför ansetts troligt att Hiro någon gång i framtiden kommer att färdas långt bak i det förflutna. ( Hiro färdas inte tillbaks i tiden utan han poserar bara med svärdet mot en dinosaurie på ett museum)
 Hiro träffar sig själv i framtiden och får reda på att Claire Bennet inte dött av Sylar.

Källor

Rollfigurer i Heroes
Fiktiva figurer från Japan
Fiktiva figurer introducerade 2006
Tidsresor på TV
WP:Projekt Japan
Fiktiva föräldralösa barn

pl:Postacie z serialu Herosi#Hiro Nakamura
fi:Luettelo televisiosarjan Heroes hahmoista#Hiro Nakamura

redpajama_set_name: RedPajamaWikipedia


PROHANDS TACTICAL is the ultimate training tool for handgun accuracy. Dry-firing is not enough. You must train your entire hand, wrist & forearm to lock on the target. PROHANDS is the #1 hand exerciser in the world thanks to spring-loaded pistons for each finger. We added a laser sight for tactical training, and the combination is key. Using is believing. Fix the red laser dot on a target 10-15 meters away, and challenge yourself to keep the laser steady on the target while exercising your fingers. Outside the range, PROHANDS TACTICAL is the most effective way to train for accuracy. Recommended by top law enforcement shooting instructors and certified NRA instructors. Available in 5 lb, 7 lb, 9 lb, and 11 lb pull weights. Comes fully assembled and includes batteries, instructions and suggested exercises. *Please note PROHANDS TACTICAL is exclusively available from Prohands.net. It is not available at retail locations, Amazon, etc.
Important: always exercise slowly and cautiously. If you experience any pain, stop immediately and see your doctor. Excessive use may cause pain or injury.


Bird watching is a great exercise any time of the year. In addition to if you like to watch birds love seeing these individuals play in your lawn and love hearing the songs that they can sing to each other then you certainly most likely want to have more of them to your garden. And it is not that difficult to do. All you have to do is always to make your garden seeing that bird friendly for the children as you possible can.
If you can manage to function that one thing they will keep return to your garden each and every day. When all is said and done parrots dont need a lot to become satisfied. Simply provide them with the basics – h2o shelter and food they will be more than written content.
Water is probably more vital for birds when compared with most mammals. This is because they need it to provide their wings a proper washing to help them fly. Parrots will typically acquire most of the water which they need through a selection of sources. They will remove it from the bugs that they eat outrageous fruits the rainfall and even the a . Water carbonators m . dew. And in freezing weather conditions they are able to melt the actual snow for mineral water.
But if you are looking to attract birds what they really love is open h2o. It attracts birds for a number of reasons. Another thing is that it provides them by having an opportunity to bathe and give their wings a good cleaning up – which helps those to fly. Thats why if you possibly could possibly find a position for a bird shower in your garden accomplish that. You will find that it will turn out attracting a lot of birds to your yard. And also in the winter time while open water can be difficult to come by in some places youll never replaced. And a heated bird bath definitely makes the difference in the world because it keeps the water via freezing to glaciers.
The second thing that chickens will be on the lookout for is actually shelter. And they want to buy for a number of reasons. Using shelter they are guarded from predators they can be protected from the wind flow and rain and it also gives them a place where they can safely assemble nests and raise their nestlings.
Birds love to find birdhouses which have been waiting and prepared for them to move in. Should you place them in your yard you can be sure that the birds will love them. As well as provide them with an additional explanation to choose your garden to improve their nestling instead of yet another place.
And finally to attract birds for a yard you will need food. During some times of year or season when there are plenty of insects around birds can find food with no problem. However at times of drought or even in really cold winter months it can be frustrating hard to find food.
Not only that but in colder weather the bird will need to overeat more calories than usual just to keep its body from closing due to hypothermia. Thus at any given time when they need the meals most they can find it is in short supply. On the other hand you can help them out by aiming feeders filled with a common foods. Once they identify the feeder you can be positive that they will make a habit of coming back to your lawn day after day. Water carbonators It can be virtually impossible to know everything you need to learn about your child whenever he or she is initially born. As a parent your current education is an continuous one as your little one develops and evolves you are also pursuing suit. Your baby is becoming much more aware of the globe around him in addition to growing stronger every single day. In turn you are starting to be educated about your baby and your role as a parent. Unfortunately you will never acquire quite comfortable with that role as there is obviously something new to learn in addition to responsibilities that you must incur. I almost found out this the hard method a few weeks after my personal daughter was born as i was introduced to the possibility of water intoxication in infants.
I thought that I ended up being fully prepared to certainly be a father and I experienced read up as much as I really could about raising an infant and I was quite confident that I had the essential education to raise my newborn daughter. While I do admit that I was quite ahead of the curve as compared to most new fathers My spouse and i almost made a grave mistake one day while i was mixing our daughters formula. Shed run out of formula and also my wife was in lunch with some of her friends well i had my little girl for the afternoon.


The Breck Epic MTB stage race has been going down this week in Breckenridge, CO. Five days of riding in a beautiful area. Tomi won himself a free entry to the race and committed to doing it on his fixed gear. He's been reporting in nightly so check out his race reports at his blog. Today is the last day so I imagine once it's all said and done he'll have a mega wrap up on the whole trip when he returns.
Outside Magazine has an interview with Chris Plesko who just set the single speed record for the Tour Divide Race finishing in 19 days. Sweet.
MB Action talks single speed racing with Fuzzy Mylne. Slow single speeders begin growing beards to see if this is the secret to speed.
Seems everyone has a single speed wrench/bottle opener these days. The tool gurus at Park offer up this one.
For over a decade I've been going up to Vermont to snowboard. After crossing the state line, as things started to turn white and the steepness of the mountains increased, I'd admire the landscape and drool over the mountain biking possibilities, year after year promising myself to make the trip up in the summer and tap into some singletrack. With friends heading up for an extended stay in the green state, an invitation to visit and no vacations planned, a low budget get-away plan with my wife was hatched. Head up for a week, ride for four of those days and return on July 4th. The Kingdom Trails, an IMBA Epic, was a place I've been hearing about for quite a while and that would be the centerpiece of riding with other various trails thrown in for good measure.
First stop on the trip was a quick detour to Centralia, PA. Fascinating but tragic story. After viewing the smoldering landscape, we were back on the road. We were hammered by torrential downpours in New York state and the forecast for the remainder of the week showed rain as well but I remained optimistic that the weather forecasters would do what they normally do and blow their predictions. As it turned out, they were spot on and we got rain everyday we were there. Occasional clear skies followed by some of the heaviest rain I have ever encountered. We remained optimistic while eating good food and drinking good beer and waiting out the weather.
Mid-week we forged north (we had base camp in East Poutney) towards Burlington in hopes their weather had been a bit better and a brief clear spell would allow some riding. With a little poking around we located the Shelburne Bay trails, full of slippery roots and rocks, some scattered mud patches but overall in good condition despite the slickness.
Insider info would have been helpful as it became obvious the loop would be best run counter-clockwise. With a 50% chance of getting it right, we got it wrong. No matter, it was good to get out and pedal and the views from the peak of the bluff overlooking the bay were beautiful. The amount of trail mileage out there is short but was just as well since shortly after loading the car back up massive rain unleashed itself on us as we headed to Magic Hat Brewery.
I've got to say, Magic Hat has one of the coolest tasting rooms I've been in a brewery, professionally styled more like a hip hang out than a warehouse afterthought like many places I've been. After sampling all of the offerings we got a recommendation from the bartender on where to get some food. There was a brief break in the rain as we headed into Burlington and ate at American Flatbread. Killer beer selection at this place and the high priced pizza rightly commanded the price due to the excellent taste and fresh, local ingredients. No wonder there is a 45 minute wait on a Tuesday evening. The rain, of course, had returned with a vengeance. We headed to Radio Bean for open mic night and some more beer, extending the night as long as possible to avoid going back to the wet camp site but eventually made our way back to the conveniently located camping at Mt. Philo.
At this point the biking portion of the trip was crumbling quickly and a call the next morning confirmed the Kingdom Trails were wet with more heavy rain in the forecast. We scrapped the plan to drive a couple of hours to the wet trails and took a meandering route towards base camp in search of more beer. We got shut down in our attempt to visit the Alchemist brewery due to it's late afternoon opening time and pushed on to Montpelier. A cool town with a cool bike shop (Onion River Sports). An art project throughout town was comprised of sculptures made of bike parts. Bonus! No brewpub to be found though.
The rest of the week continued the pattern of brief spells of sunshine punctuated by massive rain storms as a big weather systems continued to sit over the region. We managed to get a bit of swimming and canoeing in but there was no way any trails would be in rideable condition so the bikes sat lonely and unused. Saturday AM we rolled out of town early and headed south to drier environments and a chance for a MTB ride along the way to break up the long drive.
When mapping out our trip route I realized we could easily pass by Bethlehem, PA on one of our options. A recent Bike Magazine article highlighted some trails in the area. I did a little digging and found Salisbury Park was about 5 minutes off our route, which meant easy on/off access to make a quick stop appealing. Once on the trails a few friendly locals provided some route info and we got in a couple of hours riding before jumping back in the car and continuing our trek home. The trails were built by MTBers and it shows. Nice flow, good use of the land and overall good design. The trails are mostly rolling with a mix of buff dirt interspersed with technical bits. Thumbs up to the locals for both their trail work and friendliness, it was a good way to salvage the disappointing ride portion of the vacation.
So the trip wasn't as planned as far as biking went, but there are times things are out of your control so you've got to roll with the punches. Good people, good beer and good food made for fun times, just without the biking. Fortunately I've collected enough info that the next trip up should yield some quality riding if the weather cooperates.


Ortonville Trojans vs the Milbank Bulldogs has always been "the" rivals to watch! Ortonville Area Health Services provided some halftime fun at the game last night. Anyone could sign up for a drawing (free bag of popcorn just for signing up). Two names would be drawn and they would play against Dr. Stacy Longnecker and Dr. Grant Botker in a friendly game of DOC (a version of PIG). Those drawn also received a few prizes for playing. It was all in fun… but a bit competitive. Did Dr. Longnecker practice shooting some hoops before the event? Watch the video and you be the judge! The end of the video does include a few highlights from both the girls and boys varsity basketball games. GO TROJANS! Fun times, here on the MNbump.


text:
3101 McCully Road
Allison Park, PA 15101
Suzanna Krispli, Library Director
How do I . . . ?
AARP Health (www.aarp.org/health)
Info on drugs, insurance, and on staying healthy at 50-plus
American Association for Clinical Chemistry Cardiac Risk Assessment
(www.labtestsonline.org/understanding/analytes/cardiac_risk/glance.html)
American Cancer Society (www.cancer.org)
Includes links to clinical trials and patient support groups
American Diabetes Association (www.diabetes.org)
Along with news of the latest research, provides nutritional information and even recipes
American Heart Association (www.americanheart.org)
Features an online heart and stroke encyclopedia)
American Lung Association (www.lungusa.org)
Asthma & Allergy Foundation of America (www.aafa.org)
Centers for Disease Control and Prevention (www.cdc.gov)
The government's latest info on public health and communicable diseases is posted here
Children's Hospital of Pittsburgh (www.chp.edu)
Clinical Trials (www.clinicaltrials.gov)
Lists experimental treatments you may be eligible to receive
Family Doctor (www.familydoctor.org)
Straightforward general information from the American Academy of Family Physicians
Food and Drug Administration (www.fda.gov)
Healthfinder (www.healthfinder.gov)
A health library available in English and Spanish, sponsored by the U.S. Department of Health and Human Services
KidsHealth (www.kidshealth.org)
A foundation-sponsored site about children's health through adolescence; includes a special area for teens
Mayo Clinic (www.mayoclinic.com)
Offers online tools to help guide treatment decisions
Medicare (www.medicare.gov)
Medicare Diabetes Information (www.medicare.gov/Health/Diabetes.asp)
MedlinePlus (http://medlineplus.gov)
The National Library of Medicine's comprehensive health-information portal
National Cancer Institute (www.cancer.gov)
Provides clinical details about every type of cancer and the latest treatments
National Center for Chronic Disease Prevention and Health Promotion Diabetes Public Health Resource
(www.cdc.gov/diabetes)
National Diabetes Education Program (ndep.nih.gov)
National Institute of Allergy and Infectious Diseases (https://www.niaid.nih.gov/)
National Institute of Diabetes and Digestive and Kidney Diseases (www.niddk.nih.gov)
National Institutes of Health (www.health.nih.gov)
U.S. National Library of Medicine (www.nlm.nih.gov)
University of Pittsburgh and UPMC Health Sciences Library System (www.hsls.pitt.edu)
WebMD (www.webmd.com) A for-profit news and information service with interactive activities
The above links and descriptions are from AARP Magazine, UPMC Health Plan's "MyHealth Insight," and other health resources.
The Hampton Community Library would like to thank the Allegheny Regional Asset
District, the Township of Hampton, the Commonwealth of Pennsylvania,
and generous corporate/individual sponsors for their support.
E-mail Hampton Community Library
Web Address: http://www.hamptoncommunitylibrary.org
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Edward Bruce was born in Oxford, UK and studied at Northumbria University, where he won the Alcan Prize for Sculpture, and at the Glasgow School of Art. After his Fine Art degree he worked in London where he exhibited with the Glue Factory group. In 2008 his Ringing Banners, an Arts Council funded installation and performance in Liverpool Cathedral, formed part of Liverpool's European Capital of Culture arts programme. In recent years he has taught Modern Art History at the University of Liverpool and worked as a freelance artist educator for the Tate. While a member of Bridewell Studios he curated group shows for Liverpool Biennial Independents. He lives in Glasgow where he has recently completed a Masters in Fine Art Practice and works on solo and collaborative projects locally and internationally.
Grey Wolf Studios, 131 Craighall Road, Glasgow, G4 9TR, UK.


Viewing Posts for March 2016 9 Posts Found.
Welcome Benny Hengle - Realtor in Coldwell Banker Hunter Strongsville Office!
Save The Date! June 2nd, 2016 - Cleveland Clinic Children's Fundraiser!
Bring your Family, Friends & Business Associates out to the Ball Game to support a Great Cause! Proceeds from this Event will go to Cleveland Clinic Children's to support "Child Life Services" and the tools the staff use to educate, calm and distract young patients during difficult medical procedures.


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This time of year we celebrate the bountiful gifts of the fall harvest by gathering to share love, great food, conversation, and even a game of football. It is a special time that we give thanks for all the many gifts we receive – family, good health, abundant food, friends, jobs and time together with loved ones. Our family has a Thanksgiving tradition of expressing what we are thankful for while sitting down to our feast. We also have a blank sheet placed across the table that we draw, write or just sign our names in markers giving thanks. The sheet is a memento of the day.
As many of you travel to visit loved ones or prepare for your upcoming feast, I want to take a few moments to express my appreciation to you, and wish you a happy Thanksgiving. I'm so grateful for your part in receiving my monthly ezine gift. The purpose of the ezine is to share my insight, stories, resources and offer tools that help guide you on your journey through life. Often, I receive comments about how a particular article increased someone's awareness, or how it inspired them to take the next step. It brings me great joy to receive your feedback – thank you so much.
In addition to being thankful for the opportunity to share my wisdom with you, I am grateful for my creativity, the beautiful Colorado weather, a warm place to live, and the support of my husband, family and friends. Every day, I am grateful for just being alive, and the abundance in my life. Throughout the year, not just at Thanksgiving, my usual mealtime prayer is: I am thankful for all that I have, all that I give, and all that I receive. This meal is blessed. This brings me to a very special story.
This story is about a couple in Boluxi, Mississippi that were so grateful for the gift they received more than a year after hurricane Katrina. Recently, the Kirk of Bonnie Brae UCC in Denver, Colorado organized a group to travel to Boluxi to help rebuild the couple's home that was destroyed in the hurricane. The home's shell was intact, but the interior was unlivable, and had to be gutted. The displaced couple lived in a trailer, while the volunteers came to reconstruct their home. The Kirk group was one of many groups from all over the country that went to Boluxi. Even though the home was not finished during the groups' stay, the couple was so grateful for the work that was done – bringing them closer to moving back into their home. The generosity of this group touches my heart deeply.
All over the world, people give freely gifts to loved ones, as well as, gifts of time, food, materials, energy, expertise and money to help people in crisis. With the holiday season fast approaching, please consider giving alternative, thoughtful, heartfelt gifts that reach out to others in need. Why not give presents this holiday season to honor your family and friends that also build peace in our global village, and help protect our endangered planet. Alternative gift giving will bring you great joy and satisfaction. It's easy, here's how!
website, and read about the nonprofit agencies that support people in need. Select a group of interest to you that you'd like to support – give as little or as much as you'd like in honor of your family and friends. In doing this, you will help empower people in crisis, and help protect our planet. I thank you in advance for giving from your heart alternatively this holiday season.
Again, I appreciate you, and I am thankful for all that I have, all that I give, and all that I receive. I am blessed.
Coming in December, my audio book A Woman's Guide to Her Inner Evolution. Visit the website in late December or contact me for your copy.
Interested in group coaching and live in the Denver, Colorado area? See the Events page on the website for information about the Building Stability Group for Women Business Owners and the Women's Soup Night.