text:
EAA23C
582E65
779D3E
E06B3E
BEBEBE
MenuHome Civil Chem Mech Tech Bio Elec News
Revolutionary healthcare proposal – DigiTwins – seeks EU Flagship success
DigiTwins invited to enter the next stage of competition to become an EU Flagship for Future and Emerging Technologies and, if successful, would be financed by Horizon 2020 funding worth €1bn over 10 years
The European Commission has invited a large research initiative proposal – DigiTwins – to enter the next stage of competition to become an EU Flagship for Future and Emerging Technologies. If successful, it would be financed by Horizon 2020 funding worth €1 billion over 10 years.
It would involve collaboration with Trinity's School of Medicine, the Trinity Translational Medicine Institute (TTMI) and the Centre for Research on Advanced Nanostructures and Nanodevices (CRANN), with Professor of Molecular and Translational Medicine, Yuri Volkov, participating in the proposal as a leader of a key Workpackage focused on nanomedicine.
DigiTwins aims to revolutionise healthcare and biomedical research for the benefit of citizens and society and to contribute to Europe's Digital Single Market strategy through the creation of Digital Twins.
A personal 'Digital Twin' for every European citizen
The proposal promises to create a personal 'Digital Twin' for every European citizen. Our Digital Twins – accurate computer models of the key biological processes within every individual that keep us healthy or lead to disease – would be used to identify individually optimal therapies as well as preventive and lifestyle measures, without exposing individuals to unnecessary risks and healthcare systems to unnecessary costs.
Since its foundation, DigiTwins has grown from an innovative idea to an initiative with more than 200 partners in 32 countries and first applications of its concept in real-life trials.
In February, the DigiTwins initiative submitted a first proposal to the EC and thus took the first step, of a three-stage process, towards becoming an EU Flagship for Future and Emerging Technologies (FET). Stage two, in which a full proposal for a candidate FET-Flagship is submitted, kick-started recently with a DigiTwins partner meeting in Berlin.
If successful, DigiTwins would be financially supported by the European Commission over a one-year period to prepare for stage three: the final selection of the FET-Flagships, which are science- and technology-driven, large-scale, multidisciplinary research initiatives built around a visionary unifying goal that are promoted and financed by the European Commission.
After being given the go-ahead to move on to stage two, Professor Hans Lehrach, who leads the initiative, said: "We're a significant step closer to the establishment of a system of truly personalised healthcare and health maintenance throughout Europe, which will save millions of lives and billions of healthcare costs in the future."
Innovative nanotechnology-based solutions
Within the Workpackage focused on Nanomedicine, Trinity team leader, Professor Yuri Volkov, will develop innovative nanotechnology-based solutions for advanced biomedical imaging, highly informative diagnostics at a new sensitivity level, and personalised approaches for therapeutic drug delivery.
Nanomedicine approaches open up an opportunity to take into account specific patients' profiles and to create the individualised therapeutic strategies featuring enhanced drug efficacy and safety, by utilising precision drug delivery and controlled release mechanisms.
Trinity will closely co-operate within this Workpackage with leading academic and research centres from Germany, Italy, Norway, UK, Switzerland, Russia and others.
This will further expand the ongoing research carried out in the field by Trinity researchers, focused on the nanotechnological solutions for the benefits of healthcare. These are currently supported by several major European research grants under the H2020 funding programme.
About DigiTwins
DigiTwins is a large research initiative that aims at establishing a personal Digital Twin for every European citizen. The community consists of more than 200 partners from industry, academic and clinical research institutions in 32 different countries.
DigiTwins combines a transdisciplinary team of visionary scientists, clinicians, public health experts, policy makers, medical informatics experts, experts in Artificial Intelligence, experienced science management professionals, serial entrepreneurs, industry researchers and patient group representatives as well as experts from cross-cutting fields, such as economics, regulation, ethics, health insurance, data security and privacy. The initiative is led by Professor Hans Lehrach (Charité – Universitätsmedizin Berlin), Dr Nora Benhabiles (CEA – French Alternative Energies and Atomic Energy Commission) and Dr Rolf Zettl (BIH – Berlin Institute of Health).
http://www.engineersjournal.ie/2018/06/12/revolutionary-healthcare-proposal-digitwins-seeking-eu-flagship-success/http://www.engineersjournal.ie/wp-content/uploads/2018/06/a-abr1-1024x683.jpghttp://www.engineersjournal.ie/wp-content/uploads/2018/06/a-abr1-300x300.jpg 2018-06-12T09:08:40+00:00 David O'RiordanNewsbiomedical,European Union,Horizon,TCD
The European Commission has invited a large research initiative proposal – DigiTwins – to enter the next stage of competition to become an EU Flagship for Future and Emerging Technologies. If successful, it would be financed by Horizon 2020 funding worth €1 billion over 10 years. It would involve collaboration...
David O'Riordandoriordan@engineersireland.ieAdministratorEngineers Journal
Irish researcher awarded €150,000 from EU Professor Róisín Owens, from Glasnevin in Dublin, has been...
Irish start-up seeks funding after EU approves bone regeneration product HydroxyColl for market A bone regeneration product developed at the Royal College of...
€27m in funding secured for Irish energy research projects under Horizon 2020 Irish research institutions and industry have consistently won funding for...
Research into developing commercial applications for Terahertz imaging technologies starts The kick-off meeting of CELTA, a pan-European research project, including...
UCD to lead €4m tech-focused youth mental health research network University College Dublin (UCD) has been chosen to lead a...
Tagsbiomedical European Union Horizon TCD
«Next Post CÚRAM graduates win European Doctorate Awards for third consecutive year
€4bn for regional growth, climate action and disruptive technologies welcomed by Engineers Ireland Previous Post»
The design and construction of Rathmorrissy Junction: An analysis
Protecting the house buyer – an overview
Storm Ophelia (Part II): Planning for and managing the impact on the distribution network
Why I became an engineer: Three people tell their story
Delivering Dublin airport's North Runway – the key to Ireland's global connectivity
The role of mechanical engineering in modern biology and medicine
BAM Ireland launches €500,000 new children's hospital Community Benefit Fund
Workplace & Facilities Expo set for March 3-4 at RDS Dublin
Hub drives – the next step for modular robots
Industrial evolutions, revolutions and developing employee skillsets to compete in Industry 4.0
PM Group announces €50,000 bursary for Old Bawn Community School
Guide to specifying steel access solutions for pump stations, water and wastewater treatment plants
Is your company or university doing something
interesting or unusual in engineering?
Whether it's an appointment, job announcement, project or feature, let us know at:
doriordan@engineersireland.ie
Engineers Journal
22 Clyde Road
D04 R3N2
The Engineers Journal is a service
provided by Engineers Ireland.
The views and opinions expressed within
articles of the Engineers Journal are those
of the authors and do not necessarily
reflect the official policy or position of
Engineers Ireland and the editor
of the Engineers Journal.
Join Engineers Ireland


Address: 46 Easton Ave- Dover Heights NSW 2030, Dover-heights, NSW. See full address and map.
Address: Noranda WA 6062, Noranda, WA. See full address and map.
Address: 22 Badilla St- Innes Park QLD 4670, Innes-park, QLD. See full address and map.
Address: 17 Ourringo St- Budgewoi NSW 2262, Budgewoi, NSW. See full address and map.
Address: PO Box 425- Northgate QLD 4013, Northgate, QLD. See full address and map.
Address: 1 The Balcony Tarra Landing- Lakes Entrance VIC 3909, Lakes-entrance, VIC. See full address and map.
Address: Port Macquarie NSW 2444, Port-macquarie, NSW. See full address and map.
Address: 4 Tura Pl- Wagga Wagga NSW 2650, Wagga-wagga, NSW. See full address and map.
Address: 11 Halstead Cl- Scone NSW 2337, Scone, NSW. See full address and map.
Address: 2 Nolan Ave- Clovelly NSW 2031, Clovelly, NSW. See full address and map.
Address: Unit 1- 35 Sustainable Ave-Bibra Lake WA 6163, Bibra-lake, WA. See full address and map.
Address: Lansdowne NSW 2430, Lansdowne, NSW. See full address and map.
Address: Wyoming NSW 2250, Wyoming, NSW. See full address and map.
Address: 116 Smith St- Thornbury VIC 3071, Thornbury, VIC. See full address and map.
Address: 23 Hill Side Rd- Mt Waverley VIC 3149, Mt-waverley, VIC. See full address and map.
Address: 194 Miller St- Preston West VIC 3072, Preston, VIC. See full address and map.
Address: 704 Chambers Flat Rd- Logan Reserve QLD 4133, Logan-reserve, QLD. See full address and map.
Address: 127 Sturt St- Adelaide SA 5000, Adelaide, SA. See full address and map.
Address: Bellbird Park QLD 4300, Bellbird-park, QLD. See full address and map.
Address: PO Box 280- Gordonvale QLD 4865, Gordonvale, QLD. See full address and map.
Address: Surfside NSW 2536, Surfside, NSW. See full address and map.
Find every business listed for Bricklayers in Australia.


I have c++ application and I need to know if one file is in use by anyone. I'm ok with running any shell command, but I don't want to run lsof command for this purpose, since I think I can't safely assume that lsof will be available on all OS, or can I safely assume that?
You can assume that lsof ships on all macOS and you can also check the existence of that command before you call it, logging a nice friendly error message and or log message as you see fit if you want to code defensively.
You could also ask on a code-focused site what API exist to check for file existence if you want to go into specific C++ code (which would be off topic here), but from your question assuming you can call any command line tool, your overall design is fine to execute in a C++ program on macOS.
My friend, you might use lsof, or the builtin 'fuser'.
Not the answer you're looking for? Browse other questions tagged macos command-line filesystem development .


text:
Home > Vol 7, No 46 >	Johnson
Published in Oncotarget V7N46, Nov 15, 2016
FOXC1 identifies basal-like breast cancer in a hereditary breast cancer cohort
Jeff Johnson _, Michael Choi, Farnaz Dadmanesh, Bingchen Han, Ying Qu, Yi Yu-Rice, Xiao Zhang, Sanjay Bagaria, Clive Taylor, Armando E. Giuliano, Farin Amersi and Xiaojiang Cui
Jeff Johnson1, Michael Choi1, Farnaz Dadmanesh2, Bingchen Han1, Ying Qu1, Yi Yu-Rice1, Xiao Zhang3, Sanjay Bagaria5, Clive Taylor6, Armando E. Giuliano1,4, Farin Amersi1,4, Xiaojiang Cui1,4
1Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
2Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
3Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
4Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
5Department of Surgery, Mayo Clinic, Jacksonville, FL 32224, USA
6Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Farin Amersi, email: farin.amersi@cshs.org
Xiaojiang Cui, email: xiaojiang.cui@cshs.org
Keywords: basal-like breast cancer, immunohistochemistry, BRCA, FOXC1, PARP inhibitor
Received: June 04, 2016 Accepted: September 21, 2016 Published: September 30, 2016
Breast cancers arising in the setting of the hereditary breast cancer genes BRCA1 and BRCA2 are most commonly classified as basal-like breast cancer (BLBC) or luminal breast cancer, respectively. BLBC is an aggressive subtype of breast cancer associated with liver and lung metastases and poorer prognosis than other subtypes and for which chemotherapy is the only systemic therapy. Multiple immunohistochemical markers are used to identify the basal-like subtype, including the absence of estrogen receptor alpha, progesterone receptor, and human epidermal growth factor receptor 2. Forkhead box C1 (FOXC1) has been identified as a specific marker expressed in BLBC in general breast cancer cohorts. We examined an institutional cohort of breast cancer patients with germline BRCA1 (n=46) and BRCA2 (n=35) mutations and found that FOXC1 expression on immunohistochemical staining is associated with BRCA1 vs BRCA2 mutations [30/46 vs. 6/35]. In BRCA1 mutant tumors, FOXC1 was expressed in 28/31 BLBC tumors and 2/13 non-BLBC tumors, In BRCA2 mutant tumors, FOXC1 was expressed in 5/5 BLBC tumors and 1/30 non-BLBC tumors. In cell culture models of BRCA1-mutant breast cancer, FOXC1 is associated with increased proliferation and may serve as a marker for sensitivity to PARP-inhibitor therapy with olaparib.
FOXC1 identifies basal-like breast cancer in a hereditary breast cancer cohort | Johnson | Oncotarget
Gene expression profiling with unsupervised clustering analysis has demonstrated distinct classes within the molecular heterogeneity of breast cancers. Subsequent studies have demonstrated that these molecular classes, which include luminal A, luminal B, Her2 expressing (HER2), and basal-like breast cancer (BLBC), have significant prognostic and predictive value [1–3]. Hereditary breast cancer arising in the setting of germline mutations in BRCA1 and BRCA2 is recognized to generally sort with the BLBC and luminal subtypes of breast cancer, respectively [3, 4]. While these molecular subtypes are defined by clustering analysis of gene expression profiles, in clinical practice these molecular subtypes are approximated by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). In this classification system, tumors expressing estrogen receptor α (ERα) and/or progesterone receptor (PR) with low Ki-67 are categorized as luminal A; ER+ and/or PR+ with high Ki-67 or HER2+ are categorized as luminal B; ER-, PR-, and Her2+ by FISH are categorized as Her2+; and tumors lacking expression of these markers (ER-PR-HER2-) are "triple-negative" and categorized as BLBC [5]. This system has prognostic value and predicts response to specific endocrine or anti-HER2 therapy [6–10]. BLBC, which lacks ERα and HER2, has no recognized targeted therapy and has a relatively poor prognosis.
Additional IHC markers, such as epidermal growth factor receptor (EGFR) and basal cytokeratins, have been used to improve classification of BLBC, but these may not inform the molecular etiology of the disease and thereby may not serve as predictive markers for future therapy, and to some degree the inclusion of additional markers complicates the classification system and allows for discordant results [11–13]. The forkhead box transcription factor FOXC1 was identified in gene expression studies as a specific biomarker for BLBC. IHC expression of FOXC1 has been shown to be a specific marker for BLBC that has prognostic, even in cases of discrepancy between other IHC markers [12, 14]. Importantly, FOXC1 appears to play a functional role in BLBC, suggesting a potential role as a predictive marker for targeted therapies in development [14, 15].
Patients with germline mutations in BRCA1 have a significant risk of developing breast cancer by age 70, recently estimated at 69% (95% CI 56%-83%) [16]. Multiple studies have shown that 80-90%, of BRCA1 tumors are BLBC, as opposed to 10-15% of all tumors [2, 17, 18]. Conversely, approximately 20% of BLBC tumors show germline or somatic BRCA1 mutation [2]. This is in contrast to the second most common hereditary breast cancer, BRCA2-related breast cancer, which has a significantly different gene expression profile and is typically lower grade, is more differentiated, appears later in life, and belongs to the luminal/ER-positive subtype [4, 19]. Although both BRCA1 and BRCA2 have major functions tied to DNA repair through the homologous repair pathway, the specificity for BRCA1-related tumors to form BLBC suggests a role for BRCA1 in the regulation of genes related to that subtype. However, as patients with germline BRCA1 mutations represent a specific subclass of BLBC, it is yet to be established whether FOXC1 is also found within these tumors and whether there is a relationship between BRCA1/2 and FOXC1. In this study, we sought to demonstrate the clinicopathologic significance of FOXC1 expression in BRCA-associated breast cancer.
Clinicopathologic data and immunohistochemistry
Database review from two institutions identified 46 tumor samples from patients with germline BRCA1 mutations and 35 tumor samples from patients with germline BRCA2 mutations from 1995 to 2013 with available tissue for immunohistochemistry (IHC) staining. Paraffin-embedded tissue sections underwent IHC using a validated monoclonal FOXC1 antibody [14]. FOXC1 staining was considered positive if greater than 15% of cells demonstrated nuclear staining for FOXC1 (Figure 1). Available demographic and clinical information is noted in Table 1. FOXC1 association with the BLBC subtype was consistent with prior studies of BLBC demonstrating younger age of onset, higher tumor grade, and increased Ki67%. Also previously demonstrated, FOXC1-associated tumors had fewer lymph node metastases [20]. However, no significant differences were seen in the rates of distant metastases, distant recurrence, disease-free survival, or overall survival, although a trend was seen towards increased locoregional recurrence in FOXC1+ tumors (p=0.0512) (Supplementary Table S1). This may reflect relatively short follow-up times, a benefit of increased surveillance, early detection with lead-time bias, and/or more aggressive treatment among the BRCA-mutant population at our hospital.
Figure 1: FOXC1 immunohistochemistry, BRCA1/2 mutation status, and molecular subtype. A. BRCA1 mutant, basal molecular subtype with positive nuclear staining. B. BRCA wild-type, basal molecular subtype with strong nuclear positivity. C. BRCA2 mutant, luminal A molecular subtype with negative staining. D. BRCA wild-type, luminal A molecular subtype with negative staining. All images 200X. E. Distribution of BLBC/NonBLBC among FOXC1 IHC positive or negative cells for BRCA1 mutant and BRCA2 mutant tumors. BLCB: Basal-like breast cancer. NonBLBC: Non basal-like breast cancer, including Her2+ and Luminal A and Luminal B tumors.
Table 1: Clinicopathologic data for patients with BRCA mutation status and FOXC1 staining
FOXC1 +
FOXC1 −
No. of patients
Age at diagnosis (mean years ± SD)
42.9 ± 13.3
Tumor Size (mean mm ± SD)
20 ± 14
0.286**
Tumor Grade
<0.0001†
ER Positive
<0.0001‡
PR Positive
Ki67 % (mean ± SD)
<0.0001**
*t-test. ** Mann-Whitney U test. †Fisher's Exact test. ‡Chi-Square test.
Figure 1 demonstrates the relationship between BRCA mutation status, FOXC1 staining, and molecular subtypes. FOXC1 staining was significantly associated with the basal-like phenotype defined by IHC markers (ER-PR-HER2-/EGFR+/CK5/6+): 92% (33/36) of FOXC1+ tumors were basal, and nearly all basal tumors (92%; 25/28), demonstrated FOXC1 staining (p<0.0001). Mutations in BRCA1 and BRCA2 were determined as part of patients' usual care with assays performed by Myriad Genetics (Salt Lake City, UT). Consistent with the associated subtypes, FOXC1 was significantly associated with the presence of BRCA1 germline mutation and absence of BRCA2 mutation (p<0.0007). Interestingly, 67% (31/46) of BRCA1 tumors were BLBC, a percentage lower than that reported in other studies [17]. Of the 46 BRCA1 tumors, 30 expressed FOXC1 and 28 of these were BLBC. Among the 35 BRCA2 tumors, six tumors expressed FOXC1 and five were BLBC. These findings demonstrate that FOXC1 is associated with BRCA1-mutant tumors and identifies the BLBC subtype in patients with germline BRCA1/2 mutations.
Gene expression data
This association is also seen in mRNA expression data. Using the publicly available gene expression data from Larsen et al. (GSE40115), which includes gene expression profiling of 183 breast tumors, including 33 with BRCA1 germline mutation, 22 with BRCA2 germline mutation, and the remainder sporadic [21], we determined levels of FOXC1 between BLBC and non-BLBC for the BRCA1-mutant (Figure 2A) and BRCA2-mutant (Figure 2B) tumors. FOXC1 is markedly higher in BLBC compared to non-BLBC for both sets of tumors (p<0.0001).
Figure 2: FOXC1 associated with BLBC with functional significance. FOXC1 mRNA is significantly higher in basal-like breast cancer in both patients with both BRCA1 A. and BRCA2 B. mutations.
Cell proliferation and olaparib sensitivity
To determine whether FOXC1 has functional significance in BRCA1-mutant cells, we performed proliferation assays using control and CRISPR-mediated FOXC1-knockout (FOXC1-KO) SUM149 BRCA1-mutant BLBC cells (Figure 3A, Supplementary Figure S1), demonstrating decreased proliferation with FOXC1 knockout (Figure 3B). We also examined sensitivity of BRCA1-mutant cells to olaparib, a PARP inhibitor used in BRCA-mutant cancers to take advantage of synthetic lethality with the homologous repair defect. Control wild-type (WT) SUM149 cells were more sensitive to treatment with 10μM olaparib relative to DMSO vehicle than FOXC1-KO cells (Figure 3C). In examining the four available BRCA1-mutant BLBC cell lines and one BRCA1 wild-type cell line, we found that the BRCA1 mutant cell lines with relatively higher expression of FOXC1 demonstrated sensitivity to 10μM olaparib, whereas HCC1937, a BRCA1-mutant cell line with low FOXC1 expression, did not exhibit sensitivity (Figure 4B). BT549, a BLBC BRCA1 wild-type cell line with high FOXC1 levels (Figure 4A) also did not exhibit sensitivity to olaparib. Combined, these results suggest that FOXC1 is essential for BRCA1-mutant breast cancer cell growth and may predict sensitivity to treatment with olaparib in BRCA1-mutant cells, which warrants further validation using clinical samples.
Figure 3: FOXC1 knockdown diminishes proliferation. A. Western blot demonstrating CRISPR knockout of FOXC1 in SUM149. High-FOXC1 BLBC cell line BT549 and low-FOXC1 luminal cell line BT474 used as qualitative controls. B. FOXC1 knockdown results in diminished proliferation compared to FOXC1 wildtype in SUM149 cells. Mean ±SD for representative experiment with 6 technical replicates. Statistical significance for the difference in fold-change luminescence between parental and knockout cells, p<0.01 calculated by Mann-Whitney U test, reached on day 2 of growth. C. SUM149 FOXC1 wild-type cells are more sensitive to olaparib than FOXC1 knockout cells. Ratio of means ± combined SD for p<0.01 calculated by Mann-Whitney U test reached on day 3 of treatment.
Figure 4: BRCA1-mutant cell line intrinsic FOXC1 level associated with PARPi sensitivity. A. Relative FOXC1 mRNA expression for BRCA1-mutant cell lines and BRCA1 wild-type basal-like cell line BT549. Note Y-axis has been truncated for BT549 expression. BT549 FOXC1 expression significantly greater than all other cell lines (p<0.0001). HCC1937 FOXC1 expression significantly less than all other cell lines (p<0.01). B. Sensitivity of BRCA1 mutant cell lines and BT549 to olaparib. Ratio of means ± combined SD. p<0.01 calculated by Mann-Whitney U test reached on day 3 of treatment.
Prior work has demonstrated a number of genes specifically upregulated in BLBC, although the mechanism of the BLBC phenotype in BRCA1-mutant cancer is yet to be defined. We have demonstrated that FOXC1 can specifically identify BRCA1-mutant BLBC cancer. This and prior data suggests that the BLBC phenotype, and FOXC1 specifically can be regulated by BRCA1 [22]. In addition, the enrichment of FOXC1 and BLBC in BRCA1-mutant tumors may also be explained by development of cancer in FOXC1-expressing luminal progenitor cells, which are enriched in the setting of BRCA1 mutation [23, 24].
FOXC1 is known to play a critical role in embryonic ocular and brain development, with mutations or deletions resulting in glaucoma-related ocular dysgenesis and Dandy-Walker malformations [25]. Recently, FOXC1 has been demonstrated across a number of tissues to regulate the stem cell niche and stem cell activation/quiescence [26–29]. FOXC1 is also expressed in the developing mammary gland, but its exact function has not been described [23, 30]. FOXC1 is also being recognized in a wide range of cancers, including acute myeloid leukemia [31], hepatocellular carcinoma [32], renal cell carcinoma [33], gastric cancer [34], and non-small cell lung cancer [35].
In breast cancer, we have demonstrated that FOXC1 plays a role in proliferation in BRCA1-mutant BLBC cells, and prior studies have demonstrated a critical role for FOXC1 in the functional properties of BLBC, driving metastasis, epithelial-mesenchymal transition phenotype, and tumorigenesis [12, 36–39]. Our data shows that BRCA1-mutant SUM149 FOXC1 KO cells continue to proliferate, albeit at a reduced rate, suggesting that other FOXC1-independent pathways may be involved in the proliferation of these cells.
Further, FOXC1 is critical for EGFR-mediated cell proliferation and survival regulated via the ERK and PI3K/Akt pathways [40]. Downstream, FOXC1 have been shown to induce NF-κB signaling and induction of a SMO-independent Gli2 signaling pathway [15, 39]. Because of the critical role of FOXC1 in BLBC cell function, along with an opposing expression pattern between BRCA1- and BRCA2-mutant breast cancers, it is speculated that BRCA1, not BRCA2, mutation-elicited signaling might synergize with FOXC1 action in mammary tumorigenesis. One possible implication of this finding is heterogeneity in the phenotype, and possibly the cells of origin, of germline BRCA-mutation associated tumors. The mammary epithelium is sorted into subgroups representing different stages in the differentiation of tissue from mammary stem cells to one of the mature downstream pathways, basal myoepithelial cells or mature luminal cells [41]. Multiple studies suggest that BRCA1 is essential for the differentiation and maturation of luminal cells, and that BRCA1 mutation may lead to an arrest in differentiation and increase in the number of stem and/or progenitor cells [24, 41, 42]. This is significant as the different molecular subtypes have been correlated with different cells of origin along, with BLBC associated with luminal progenitor cells and luminal cancers associated with mature luminal epithelial cells [24, 43]. The presence of FOXC1, which was shown to be induced in luminal progenitor cells, suggests that germline BRCA mutations may cooperate with FOXC1 to induce tumorigenesis in the BLBC subgroup of BRCA-mutant breast cancer.21 The heterogeneity demonstrated especially in BRCA1 associated tumors may affect therapeutic options and requires further investigation.
This study also demonstrates that expression of FOXC1 in BRCA1 mutant cell lines correlates with sensitivity to olaparib. Whether this is due to rates of proliferation or another mechanism is yet to be explored, but this, and the specificity of FOXC1 in BRCA1-mutant tumors, suggests a possible role for FOXC1 as a marker for targeted therapy. Certainly the BRCA1-FOXC1 axis deserves further attention as a mechanism for the etiology of BLBC, and ultimately may prove FOXC1 as a marker for targeted therapies against BRCA1 and/or BLBC.
Data on molecular subtype as well as ERα, PR, Her2, and Ki-67 was collected from pathology reports from surgically resected tumor specimens. IHC of ERα, PR, Her2, Ki-67, EGFR, and CK5/6 was performed as part of routine surgical pathology of tumor specimens. IHC staining and interpretation was performed consistent with guidelines published by the American Society of Clinical Oncology/College of American Pathologists [44]. Tissue sections demonstrating any intensity of ER or PR staining (low, moderate, high) in ≥1% of cells were reported as "positive." Ki-67 is reported as a percentage of cells demonstrating nuclear staining, and tumors with ≥20% of cells staining positive are interpreted as "high."[45] Tumors expressing estrogen receptor α (ERα) and/or progesterone receptor (PR) with low Ki-67 were categorized as luminal A; ERα + and/or PR+ with high Ki-67 or HER2+ were categorized as luminal B; ERα -, PR-, and Her2+ by FISH were categorized as Her2+; and tumors lacking expression of ERα, PR, and HER2 with expression of EGFR and CK5/6 were categorized as BLBC [5, 13, 46]. FOXC1 status was determined by staining of archived formalin-fixed paraffin-embedded breast cancer tissue from surgical specimens using a validated monoclonal FOXC1 antibody (Onconostic Technologies, Inc., Champaign, IL).12 Two independent pathologists blinded to BRCA status assessed slides for nuclear staining of FOXC1 and determined the percentage of positive cells. Sections demonstrating positive nuclear staining in ≥15% of cells were deemed positive for FOXC1 staining.
Gene expression arrays
Data from Larsen et al. (GSE40115) was obtained from the Gene Expression Omnibus [21]. Z-scores for gene expression levels were compared with the Mann-Whitney U test.
Proliferation assays
Cells were seeded at 1 × 103 cells/wellin 96 well plates. SUM149 cells were cultured in Ham's F12 nutrient mixture, 5% fetal bovine serum, and 1% penicillin/streptomycin, supplemented 0.01 mg/ml insulin and 500 ng/ml hydrocortisone [47]. Luminescence, based on quantity of ATP present, was used a readout for measuring number of viable cells and was determined every 24 hours using CellTiter-Glo Assay (Promega) according to manufacturer protocols. Daily luminescence values were normalized to Day 0 and compared using Mann-Whitney U test. A single experiment included six technical replicates and all experiments were repeated three times. Data shown are mean±SD from a representative experiment.
Drug sensitivity
Cells were seeded at 1 × 103 cells/well (BT549), 2 × 103 cells/well (SUM1315, HCC1937), 3 × 103 cells/well (SUM149), or 4 × 103 cell/well (MDA-MB-436) in 96 well plates. Cells were cultured according to previously published protocol [47]. Cells were treated 24 hours after plating with 1μM olaparib in DMSO or equivalent volume of DMSO. Relative cell number was assessed with CellTiter-Glo Assay (Promega) every 24 hours. Daily luminescence values were normalized to Day 0 and are expressed as the ratio of mean values for luminescence for olaparib treated/DMSO treated cells for each cell line on a given treatment day ±combined SD. A single experiment included six technical replicates and all experiments were repeated three times. Data are from a representative experiment. Daily luminescence values were compared using Mann-Whitney U test.
FOXC1 knockout cells
The knockout of FOXC1 in SUM149 cells was performed according to the protocol published previously [48]. Briefly, the single guide RNA (sgRNA) for knocking down FOXC1 was designed by an online tool (http://crispr.mit.edu/). The sequence of the sgRNA is 5'-GGGTGCGAGTACACGCTCAT-3'. The sgRNA and its complementary strand were synthesized (ThermoFisher), annealed, and then subcloned into LentiCRISPRv2 vector (Addgene). The cells were infected with LentiCRISPRv2-FOXC1 and then selected with puromycin for 48 hours. The knockout efficiency was evaluated by western blotting.
Total RNA was extracted and reverse transcription performed using the RNeasy Mini Kit (Qiagen) the QuantiTect Reverse Transcription Kit (Qiagen) according to manufacturer's instructinos. Quantitative PCR was done using an iCycler iQ Real-Time Thermocycler (Bio-Rad Laboratories) [15]. GAPDH was used as an internal control. FOXC1 primers used were: 5'-catccgccacaacctctcgct-3' (forward) and 5'-gtgcagcctgtccttctcctcc-3' (reverse). Fold change was calculated with delta delta Ct value. Bar graphs represent mean±SEM of three independent experiments with three technical replicates. Pairwise comparisons analyzed with Tukey's HSD.
Data were analyzed as described using GraphPad Prism version 6 for Windows (GraphPad Software, La Jolla, CA USA) or JMP version 12 for Windows (SAS Institute, Inc., Cary, NC USA). For all statistics, p<0.05 was used for statistical significance. For clinicopathologic variables, normally distributed variables were compared with 2-tailed t-test and non-normally distributed variables with the Mann-Whitney U test. Fisher's Exact test was used for mean comparisons between >2 groups. Chi-Square test was used to compare proportions.
X. Cui is a named inventor on patent applications regarding the role of FOXC1 in cancer. The other authors declare that no conflict of interest exists.
X.C. is supported by National Institutes of Health (CA151610), the Avon Foundation (02-2014-063), Eleanor and Glenn Padnick Discovery Fund in Cellular Therapy, and David Salomon Translational Breast Cancer Research Fund, and the Entertainment Industry Foundation. Giuliano is supported by the Fashion Footwear Charitable Foundation of New York, Inc., Associates for Breast and Prostate Cancer Studies, and the Margie and Robert E. Petersen Foundation. The funders/sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
J.J, F.A., and X.C. conceived and designed the experiments. J.J. performed experiments. M.C., B.H, Y.Q. and Y.Y. assisted with the experiments. F.D. and C.T. performed FOXC1 IHC and analysis. S.B., C.T., F.A., and A.G participated in experimental design, contributed patient data, and participated in manuscript preparation. J.J. and X.C wrote, revised, and edited the manuscript.
1. van't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002; 415:530-536. doi: 10.1038/415530a.
2. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012; 490:61-70. doi: 10.1038/nature11412.
3. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, et al. Molecular portraits of human breast tumours. Nature. 2000; 406:747-752. doi: 10.1038/35021093.
4. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proceedings of the National Academy of Sciences of the United States of America. 2003; 100:8418-8423. doi: 10.1073/pnas.0932692100.
5. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B and Senn HJ. Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Annals of oncology. 2011; 22:1736-1747. doi: 10.1093/annonc/mdr304.
6. Barnes DM, Skinner LG and Ribeiro GG. Triple hormone-receptor assay: a more accurate predictive tool for the treatment of advanced breast cancer? British journal of cancer. 1979; 40:862-865.
7. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet. 1998; 351:1451-1467.
8. Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, Moy B and Bardia A. Neoadjuvant Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-analysis. JAMA oncology. 2016. doi: 10.1001/jamaoncol.2016.1897.
9. Stocker A, Hilbers ML, Gauthier C, Grogg J, Kullak-Ublick GA, Seifert B, Varga Z and Trojan A. HER2/CEP17 Ratios and Clinical Outcome in HER2-Positive Early Breast Cancer Undergoing Trastuzumab-Containing Therapy. PloS one. 2016; 11:e0159176. doi: 10.1371/journal.pone.0159176.
10. Pegram MD, Lipton A, Hayes DF, Weber BL, Baselga JM, Tripathy D, Baly D, Baughman SA, Twaddell T, Glaspy JA and Slamon DJ. Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. Journal of clinical oncology. 1998; 16:2659-2671.
11. Ray PS, Bagaria SP, Wang J, Shamonki JM, Ye X, Sim MS, Steen S, Qu Y, Cui X and Giuliano AE. Basal-like breast cancer defined by FOXC1 expression offers superior prognostic value: a retrospective immunohistochemical study. Annals of surgical oncology. 2011; 18:3839-3847. doi: 10.1245/s10434-011-1657-8.
12. Ray PS, Wang J, Qu Y, Sim MS, Shamonki J, Bagaria SP, Ye X, Liu B, Elashoff D, Hoon DS, Walter MA, Martens JW, Richardson AL, et al. FOXC1 is a potential prognostic biomarker with functional significance in basal-like breast cancer. Cancer research. 2010; 70:3870-3876. doi: 10.1158/0008-5472.CAN-09-4120.
13. Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, Perou CM and Nielsen TO. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clinical cancer research. 2008; 14:1368-1376. doi: 10.1158/1078-0432.CCR-07-1658.
14. Jensen TW, Ray T, Wang J, Li X, Naritoku WY, Han B, Bellafiore F, Bagaria SP, Qu A, Cui X, Taylor CR and Ray PS. Diagnosis of Basal-Like Breast Cancer Using a FOXC1-Based Assay. Journal of the National Cancer Institute. 2015; 107. doi: 10.1093/jnci/djv148.
15. Wang J, Ray PS, Sim MS, Zhou XZ, Lu KP, Lee AV, Lin X, Bagaria SP, Giuliano AE and Cui X. FOXC1 regulates the functions of human basal-like breast cancer cells by activating NF-kappaB signaling. Oncogene. 2012; 31:4798-4802. doi: 10.1038/onc.2011.635.
16. Rebbeck TR, Mitra N, Wan F, Sinilnikova OM, Healey S, McGuffog L, Mazoyer S, Chenevix-Trench G, Easton DF, Antoniou AC, Nathanson KL, Laitman Y, Kushnir A, et al. Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. Jama. 2015; 313:1347-1361. doi: 10.1001/jama.2014.5985.
17. Foulkes WD, Stefansson IM, Chappuis PO, Begin LR, Goffin JR, Wong N, Trudel M and Akslen LA. Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. Journal of the National Cancer Institute. 2003; 95:1482-1485. doi: 10.1093/jnci/djg050.
18. Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X and Perou CM. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast cancer research. 2010; 12:R68. doi: 10.1186/bcr2635.
19. Hedenfalk I, Duggan D, Chen Y, Radmacher M, Bittner M, Simon R, Meltzer P, Gusterson B, Esteller M, Kallioniemi OP, Wilfond B, Borg A, Trent J, et al. Gene-expression profiles in hereditary breast cancer. The New England journal of medicine. 2001; 344:539-548. doi: 10.1056/NEJM200102223440801.
20. Crabb SJ, Cheang MC, Leung S, Immonen T, Nielsen TO, Huntsman DD, Bajdik CD and Chia SK. Basal breast cancer molecular subtype predicts for lower incidence of axillary lymph node metastases in primary breast cancer. Clinical breast cancer. 2008; 8:249-256. doi: 10.3816/CBC.2008.n.028.
21. Larsen MJ, Kruse TA, Tan Q, Laenkholm AV, Bak M, Lykkesfeldt AE, Sorensen KP, Hansen TV, Ejlertsen B, Gerdes AM and Thomassen M. Classifications within molecular subtypes enables identification of BRCA1/BRCA2 mutation carriers by RNA tumor profiling. PloS one. 2013; 8:e64268. doi: 10.1371/journal.pone.0064268.
22. Tkocz D, Crawford NT, Buckley NE, Berry FB, Kennedy RD, Gorski JJ, Harkin DP and Mullan PB. BRCA1 and GATA3 corepress FOXC1 to inhibit the pathogenesis of basal-like breast cancers. Oncogene. 2012; 31:3667-3678. doi: 10.1038/onc.2011.531.
23. Sizemore GM, Sizemore ST, Pal B, Booth CN, Seachrist DD, Abdul-Karim FW, Kume T and Keri RA. FOXC1 is enriched in the mammary luminal progenitor population, but is not necessary for mouse mammary ductal morphogenesis. Biology of reproduction. 2013; 89:10. doi: 10.1095/biolreprod.113.108001.
24. Liu S, Ginestier C, Charafe-Jauffret E, Foco H, Kleer CG, Merajver SD, Dontu G and Wicha MS. BRCA1 regulates human mammary stem/progenitor cell fate. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105:1680-1685. doi: 10.1073/pnas.0711613105.
25. Aldinger KA, Lehmann OJ, Hudgins L, Chizhikov VV, Bassuk AG, Ades LC, Krantz ID, Dobyns WB and Millen KJ. FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nature genetics. 2009; 41:1037-1042. doi: 10.1038/ng.422.
26. Omatsu Y, Seike M, Sugiyama T, Kume T and Nagasawa T. Foxc1 is a critical regulator of haematopoietic stem/progenitor cell niche formation. Nature. 2014; 508:536-540. doi: 10.1038/nature13071.
27. Lambers E, Arnone B, Fatima A, Qin G, Wasserstrom JA and Kume T. Foxc1 Regulates Early Cardiomyogenesis and Functional Properties of Embryonic Stem Cell Derived Cardiomyocytes. Stem cells (Dayton, Ohio). 2016; 34:1487-1500. doi: 10.1002/stem.2301.
28. Lay K, Kume T and Fuchs E. FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential. Proceedings of the National Academy of Sciences of the United States of America. 2016; 113:E1506-1515. doi: 10.1073/pnas.1601569113.
29. Wang L, Siegenthaler JA, Dowell RD and Yi R. Foxc1 reinforces quiescence in self-renewing hair follicle stem cells. Science. 2016; 351:613-617. doi: 10.1126/science.aad5440.
30. Stute P, Sielker S, Wood CE, Register TC, Lees CJ, Dewi FN, Williams JK, Wagner JD, Stefenelli U and Cline JM. Life stage differences in mammary gland gene expression profile in non-human primates. Breast cancer research and treatment. 2012; 133:617-634. doi: 10.1007/s10549-011-1811-9.
31. Somerville TD, Wiseman DH, Spencer GJ, Huang X, Lynch JT, Leong HS, Williams EL, Cheesman E and Somervaille TC. Frequent Derepression of the Mesenchymal Transcription Factor Gene FOXC1 in Acute Myeloid Leukemia. Cancer cell. 2015; 28:329-342.
32. Xia L, Huang W, Tian D, Zhu H, Qi X, Chen Z, Zhang Y, Hu H, Fan D, Nie Y and Wu K. Overexpression of forkhead box C1 promotes tumor metastasis and indicates poor prognosis in hepatocellular carcinoma. Hepatology. 2013; 57:610-624. doi: 10.1002/hep.26029.
33. Yao T, Wang Q, Zhang W, Bian A and Zhang J. Identification of genes associated with renal cell carcinoma using gene expression profiling analysis. Oncology letters. 2016; 12:73-78. doi: 10.3892/ol.2016.4573.
34. Xu Y, Shao QS, Yao HB, Jin Y, Ma YY and Jia LH. Overexpression of FOXC1 correlates with poor prognosis in gastric cancer patients. Histopathology. 2014; 64:963-970. doi: 10.1111/his.12347.
35. Wei LX, Zhou RS, Xu HF, Wang JY and Yuan MH. High expression of FOXC1 is associated with poor clinical outcome in non-small cell lung cancer patients. Tumour biology. 2013; 34:941-946. doi: 10.1007/s13277-012-0629-3.
36. Taube JH, Herschkowitz JI, Komurov K, Zhou AY, Gupta S, Yang J, Hartwell K, Onder TT, Gupta PB, Evans KW, Hollier BG, Ram PT, Lander ES, et al. Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107:15449-15454. doi: 10.1073/pnas.1004900107.
37. Powell AA, Talasaz AH, Zhang H, Coram MA, Reddy A, Deng G, Telli ML, Advani RH, Carlson RW, Mollick JA, Sheth S, Kurian AW, Ford JM, et al. Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PloS one. 2012; 7:e33788. doi: 10.1371/journal.pone.0033788.
38. Sizemore ST and Keri RA. The forkhead box transcription factor FOXC1 promotes breast cancer invasion by inducing matrix metalloprotease 7 (MMP7) expression. The Journal of biological chemistry. 2012; 287:24631-24640. doi: 10.1074/jbc.M112.375865.
39. Han B, Qu Y, Jin Y, Yu Y, Deng N, Wawrowsky K, Zhang X, Li N, Bose S, Wang Q, Sakkiah S, Abrol R, Jensen TW, et al. FOXC1 Activates Smoothened-Independent Hedgehog Signaling in Basal-like Breast Cancer. Cell reports. 2015; 13:1046-1058. doi: 10.1016/j.celrep.2015.09.063.
40. Jin Y, Han B, Chen J, Wiedemeyer R, Orsulic S, Bose S, Zhang X, Karlan BY, Giuliano AE, Cui Y and Cui X. FOXC1 is a Critical Mediator of EGFR Function in Human Basal-like Breast Cancer. Annals of surgical oncology. 2014. doi: 10.1245/s10434-014-3980-3.
41. Kubista M, Rosner M, Kubista E, Bernaschek G and Hengstschlager M. Brca1 regulates in vitro differentiation of mammary epithelial cells. Oncogene. 2002; 21:4747-4756. doi: 10.1038/sj.onc.1205580.
42. Furuta S, Jiang X, Gu B, Cheng E, Chen PL and Lee WH. Depletion of BRCA1 impairs differentiation but enhances proliferation of mammary epithelial cells. Proceedings of the National Academy of Sciences of the United States of America. 2005; 102:9176-9181. doi: 10.1073/pnas.0503793102.
43. Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, Asselin-Labat ML, Gyorki DE, Ward T, Partanen A, Feleppa F, Huschtscha LI, Thorne HJ, et al. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nature medicine. 2009; 15:907-913. doi: 10.1038/nm.2000.
44. Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Journal of clinical oncology. 2010; 28:2784-2795. doi: 10.1200/JCO.2009.25.6529.
45. Dowsett M, Nielsen TO, A'Hern R, Bartlett J, Coombes RC, Cuzick J, Ellis M, Henry NL, Hugh JC, Lively T, McShane L, Paik S, Penault-Llorca F, et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. Journal of the National Cancer Institute. 2011; 103:1656-1664. doi: 10.1093/jnci/djr393.
46. Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, Akslen LA, Ragaz J, Gown AM, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clinical cancer research. 2004; 10:5367-5374. doi: 10.1158/1078-0432.CCR-04-0220.
47. Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe JP, Tong F, Speed T, Spellman PT, DeVries S, et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer cell. 2006; 10:515-527. doi: 10.1016/j.ccr.2006.10.008.
48. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA and Zhang F. Genome engineering using the CRISPR-Cas9 system. Nature protocols. 2013; 8:2281-2308. doi: 10.1038/nprot.2013.143.

redpajama_set_name: RedPajamaCommonCrawl


text:
Home Public School Shakedown Parents Risk Dying for Dyett and Neighborhood Public Schools
Parents Risk Dying for Dyett and Neighborhood Public Schools
by Julian Vasquez Heilig
Parents and community members are entering the fourth week of a hunger strike in Chicago. While the issues may seem at first glance specific to Dyett High School, the protest is really about the top-down, private control school reform regime in Chicago and elsewhere. In essence the parents are demanding
An open-enrollment neighborhood public school.
A school that is properly resourced.
A school that is community-based and provides children 21st century skills rather than rote learning.
These are also the core issues ignored by top-down, private control school reform in New Orleans, Detroit, Tennessee etc.
A Hunger Strike in Chicago http://t.co/3fAJNBvc34 via @nytvideo
— JulianVasquezHeilig (@ProfessorJVH) September 9, 2015
I was blown away by Anna Jones', one of the parents involved in the Dyett Hunger Strike, recent testimony:
"My name is Anna Jones. I have four children. My three younger children are in elementary school, and my eighth grader will be starting high school in the fall. Mayor Rahm Emanuel closed 50 schools in "low-income neighborhoods" for "underutilization." The largest number of school closings in history.I'm no politician but I do know that schools underutilized are schools underfunded. "UNDERFUND=UNDERUTILIZE."
It doesn't take a rocket scientist to know, that if you don't invest in something, there is no use for it. That if public schools in Bronzeville were getting the same funds as public schools in Lincoln Park, that public schools would be equally utilized and not "over utilized" verses underutilize Emanuel's idea to close 50 schools devastated me and the aftermath broke my heart. School is overcrowded and filthy daily, Children eat breakfast in the hallway or the classroom sometimes the gym room, kids with disabilities receive their services under the stairwell and are often distracted, the nurse is only available on Tuesday and her office is the security guard's desk, 1 teacher's aide in the entire building with 500 students, a k-1 split class, no books, no library, nor librarian, no restorative justice, no science lab, no after school programs, absolutely no reading teacher for over 3 months in my daughter's eighth grade year, my kids being inappropriately handled by staff and the district's policy has destroyed good teacher's passion and ability to teach etc.
To add insult to injury my children were flooded with test that took away from basic instruction that did nothing to support their achievements. I didn't know what to do or where to turn but every time I looked in the eyes of my boys and girls (especially my eldest) I accepted that giving up could never be an option.
The community has been fighting for Dyett high school since 2009. In 2013 I was proud and relieved to join the Kenwood Oakland Community Organization and The Coalition to Revitalize Dyett High School. There I found hope again and a team of likeminded good people (parents, educators, organizing partners and community leaders) creating a world class plan with 2 common interests: the children and the community by which they live.
I feel like I've been robbed of my tax dollars therefore my children have been robbed of their education. I can't get that time lost back. That's why I'm committed to the fight for a community-driven Dyett Global leadership and green technology high school. Our schools and communities are impoverished and becoming more impoverished due to the misappropriation of tax payer's dollars as a plan to wipe-out low-income neighborhoods intentionally for personal profit and gain . "WE PAY TAX DOLLARS- WE'VE INVESTED IN EDUCATION JUST LIKE THE UPPER CLASS".
We will continue to fight, as long as it takes, until justice is served to our children on a platter. All children across the nation deserve a world class equal education opportunity no matter what."
The elephant in the room is that parents in wealthier areas don't have to go on hunger strikes to make these demands for their children. According to the State Board of Education, per pupil operational spending in CPS is $13,433.
What do the wealthy spend on their students in Illinois? Reboot Illinois reported which districts spend the most money per student.I think you get a feel for the very obvious disparity in the provision of education for rich and poor in Illinois. There are districts in Illinois spending almost double what CPS spends. Sadly, the disparities between the provision of rich and poor is quite similar across the United States— it's glaring. High quality education and resources are purposefully rationed for poor children on purpose, or accidentally on purpose. I once heard Brother Jitu characterize this as "sabotage." Here is how you get the latest on the hunger strike from Twitter and Facebook:
#fightfordyett #WeSupportDyett12 HUNGER STRIKE DAY 24. We will do it again tonight @ 6pm. @MHPshow @cnnbrk pic.twitter.com/Qn8siTLwTK
— Jitu Brown (@brothajitu) September 9, 2015
#fightfordyett #WeSupportDyett12 Silent march again tonight @6pm f/Dyett to Prez house. @MSNBC @cnnbrk DAY 24 pic.twitter.com/EtilIOjPzc
You can find daily updates on Brotha Jitu's Facebook page here.
These photos are also from his page.
Here is the Sac State College of Education faculty and students in solidarity with the Dyett hunger strikers.
Join the fight with solidarity fasts (See hunger strike for community-based public schools #FightForDyett) and please engage on Twitter, Facebook and other traditional and social media platforms.
Please Facebook Like, Tweet, etc and/or reblog to share this discussion with others. #FightforDyett #WeSupportDyett12
http://cloakinginequity.com/2015/09/09/parents-risk-dying-for-dyett-and-neighborhood-public-schools-fightfordyett-wesupportdyett12/
Public School Shakedown Education Resist Activism
Julian Vasquez Heilig
Professor at California State University Sacramento and blogger at Cloaking Inequity.
Read more by Julian Vasquez Heilig


Library and Archives Canada has acquired a rare 1944 book previously owned by Adolf Hitler.
The book contains data compiled by Heinz Kloss in 1944 on population statistics in certain cities as well as key organizations and presses of Canadian and American Jewish communities.
While the report hints at what might have happened in Canada had the allies lost World War 2, it also demonstrates that the Holocaust was not a purely European event, but rather an operation that was stopped before it reached North America.
The public will have a chance to view the book as part of the International Holocaust Remembrance Day Commemoration at 395 Wellington Street on Sunday, January 27, from 1:30 to 3:30 p.m. ET.


text:
New Outbreaks of Coronavirus Can Be Halted with Isolation Measures, According to Study
China is taking drastic steps to contain the spread of a recently identified coronavirus, but the outbreak has already traveled past its borders, and cities around the globe must be ready to respond to cases within their jurisdictions. Yale SOM's Edward Kaplan used early reports out of Wuhan to evaluate the likely effectiveness of common tactics, such as isolation of patients and quarantine, in keeping the disease from spreading in new regions. His model predicts that new outbreaks can likely be contained by isolating infected patients, but it also highlights the importance of identifying new cases as early as possible.
A deserted train station in Wuhan, China, on January 23, 2020. Photo: Hector Retamal/AFP via Getty Images.
Edward H. Kaplan
William N. and Marie A. Beach Professor of Operations Research, Professor of Public Health & Professor of Engineering
By Jonathan Weisberg
When the rising death count from a novel coronavirus first captured worldwide attention at the beginning of 2020, little was still known about the disease—how deadly it would be, how fast it would spread. But when an analysis of the first 425 confirmed cases was published on January 29 in the New England Journal of Medicine, it provided key clues. Edward H. Kaplan, the William N. and Marie A. Beach Professor of Operations Research, professor of public health, and professor of engineering, found in this early report enough information to create a preliminary model of how the disease spreads that might inform public health efforts around the world.
The paper Kaplan wrote over the next few days shows that effectively isolating patients with COVID-19, as the virus has since been named, should be sufficient to quell new community outbreaks. The work has been shared with health officials at federal and local levels, as well as other researchers, and is slated to be published in Health Care Management Science.
"The good news is that, in principle, case isolation alone is sufficient to end community outbreaks of [COVID-19] transmission, provided that cases are detected efficiently," Kaplan wrote. But he stresses that officials need to prepare and be ready to act if an outbreak appears. Ensuring that hospitals have capacity, public education about COVID-19 symptoms, and strict hygiene practices will all be important. One other takeaway from the study is counterintuitive: as suggested earlier by others, Kaplan recommends that as many people as possible get a flu shot. It won't prevent COVID-19, but fewer influenza infections will reduce the stress on the healthcare system and make it easier to identify cases of COVID-19, which has many similarities to the flu.
Read the paper: "Containing 2019-nCoV (Wuhan) Coronavirus"
To build his probability models, Kaplan used data from the NEJM paper, such as the exponential growth rate in newly identified cases and the incubation time from infection to the appearance of symptoms, to calculate the transmission rate curve, which shows how many additional people are likely to be infected by one person with COVID-19 over time since infection.
New infections per day from a single case of COVID-19 as a function of time from infection.
"The area under this entire curve is the total number of infections you would expect a single newly infected person to transmit to others at the start of an epidemic, before there have been any interventions," says Kaplan.
The total new infections per person for an infectious disease is called the reproductive number, abbreviated R0. Without intervention, the model showed, COVID-19 has an R0 of 2.26. This was worrisome. An R0 value greater than 1 indicates that an outbreak is likely to expand, as each infected person transmits the virus to more people; a value less than 1 indicates that the outbreak will likely diminish.
Without a vaccine available, the best way to bring down the R0 value is through containment procedures, including isolation and quarantine. Kaplan created a version of the model that assumes people seek treatment and are isolated as soon as they show symptoms. Symptoms appear at 5.2 days after infection on average but can take as long as two weeks.
"Once you isolate patients, you put them in a negative pressure room in a hospital so that nothing can come out. And you keep them there until you're convinced that they have lost an infection," Kaplan says. In this situation, infected people no longer pass on the disease once they are isolated, removing all the new infections after the detection time.
Isolation when symptoms are detected prevents new infections. In the example above, symptoms are detected at 5.2 days; new infections prevented are shaded in blue.
Under these assumptions, R0 is reduced by more than three-quarters to .48. That is well under 1, indicating the outbreak would likely be contained.
But Kaplan notes that this is a "best-case scenario"—it assumes that people seek treatment as soon as they detect symptoms and doesn't leave room for people thinking they only have the flu or having trouble getting to a healthcare provider. So, he doubled the detection time before isolation: the new mean becomes 10.4 days but it could take as long as four weeks to detect. In that scenario, the ill person goes on infecting others for several additional days, and R0 only falls to 1.1, not enough to get the infection under control.
This difference highlights the importance of early identification and action. "The real message is the importance of rapid (self) detection," Kaplan wrote in his paper. He points out that widespread media reports about the disease and public information campaigns mean that people who are infected are more likely to suspect it and seek treatment promptly.
Another critical question is how long to keep people in isolation. Release them too soon and they can continue to spread the infection. Kaplan found that a seven-day isolation was likely insufficient, while a 14-day isolation brought the R0 down to nearly the same level as indefinite isolation in the optimistic case of detection at the time disease symptoms appear.
Kaplan used similar techniques to assess the effectiveness of contact tracing and quarantine—locating and restricting the movements of apparently healthy people who may have come in contact with someone infected with COVID-19. He found that this approach is less effective than isolation, only reducing R0 to .93 under very optimistic assumptions. Simultaneously enforcing isolation and quarantine leads to better results overall, though the effect is "sub-additive" – the marginal impact of quarantine given isolation is less than the impact of quarantine alone.
Kaplan's conclusion that a new COVID-19 outbreak can likely be contained with isolation of infected patients may seem at odds with the scale of the outbreak in China. "You might ask why that hasn't happened in Wuhan," he says. "The answer is because, by the time people figured out what was going on, they were overrun with this enormous caseload… One of the real tragedies in China is that so many healthcare workers have been infected and in some cases have died. But if you start at the beginning, and it's a small outbreak, and you recognize that's what it is quickly, and you can put these things into practice, then my calculations suggest that it is definitely containable."
Department: Research
Explore more in Healthcare
A Long-Term Solution to Insuring the Sick
Soheil Ghili
Vision and Equity
Howard P. Forman, Harlan M. Krumholz, Kristen Nwanyanwu
Pushing Medicine into the Future
Howard P. Forman, Harlan M. Krumholz, Eric Topol
The Power of Mentorship
Nancy J. Brown, Howard P. Forman, Harlan M. Krumholz
Reinventing Medical Education
Vineet Arora, Harlan M. Krumholz, Howard P. Forman


The GIGA German Institute of Global and Area Studies, in cooperation with the Centre for the Study of Governance Innovation (GovInn) at the University of Pretoria is organizing a two-day workshop on the legacy of armed conflicts: Southern African and comparative perspectives.
Achieving stable peace, building accountable state institutions and (re)establishing trust are core challenges in the aftermath of an armed conflict. While violent conflicts are disruptive, they also offer opportunities for political and social change. However, the passage from conflict to sustainable peace is a complicated process. Formal and informal processes taking place during the war and in its immediate aftermath can have profound long-term implications. Even in Southern Africa, which has been heralded as a 'success story' of peacebuilding, past wars continue to shape politics and societies in many ways.
The Workshop will feature lectures from two distinguished keynote speakers as well as a roundtable on the legacy of armed conflicts and apartheid in Southern Africa. Participants are invited to present their research in thematic parallel sessions.
The first keynote lecture will be delivered by Prof. Timothy Sisk from the Josef Korbel School of International Studies at the University of Denver. Prof. Sisk is a leading peace and conflict scholar. He has authored numerous books and articles on conflict resolution and peacebuilding in South Africa and in many other parts of the world, including Democratization in South Africa: The Elusive Social Contract (1995, Princeton University Press), From War to Democracy: Dilemmas of Peacebuilding (co-edited with Anna Jarstad , Cambridge University Press, 2008) and The Dilemmas of Statebuilding: Confronting the Contradictions of Postwar Peace Operations (co-edited with Roland Paris, Routledge, 2009).
The second keynote lecture will be delivered by Prof. Gilbert Khadiagala. Prof. Khadiagala is currently Jan Smuts Professor of International Relations and Head of the Department at the University of Witwatersrand. He was formerly Associate Professor at the Paul H. Nitze School of Advanced International Studies (SAIS), Johns Hopkins University. Prof. Khadiagala is a prominent expert of peace and security issues in Sub-Saharan and has authored many academic and policy-oriented publications on Southern Africa, the Great Lakes Region and Eastern Africa.


text:
Jessie Denning
The adventures of a first-time homesteader
By Jessie Denning
Issue #160 • July/August, 2016
In November of 2015, my husband and I moved onto our 50-acre parcel of land in a 28-foot travel trailer — with no knowledge of homesteading except what we've read in the pages of Backwoods Home Magazine. Within a couple months of moving, we tore down the ramshackle, 1920s-era house on the property, using only hand tools and a small tractor we borrowed from my father-in-law. We then developed a spring near the house, built a shed to house the pump for it (and provide much-needed storage), and got the numerous required permits to build a new house on top of where the old one stood.
It's been a whirlwind of activity, with my husband and I both working full-time and devoting weekends to working on our property. My husband, Tim, has a degree in Forest Management and works as a wildland firefighter during the summer. He has big plans to grow trees so we can provide our own lumber, but for now, he's the one in charge of cutting down dead trees and burning all the brush piles.
The new house
Once our permit applications were processed and our bank loan came through, the contractors started working on our house. Although it is my dream to one day build my own house, our county planning department allows only one year in which to replace an old dwelling with a new one — not enough time for a novice builder to construct a house. Instead, we hired a construction company to build it. Here's a tip: If you build a big, square house with four corners, it's cheaper than building a smaller house with more corners.
Reclaiming the land
Since we didn't have to work on building our house, my husband and I turned our efforts to something much less glamorous: clearing brush and hauling trash. I never realized how much of a homesteader's job is simply reclaiming land that has been overrun with weeds. The previous owners had also left huge heaps of garbage lying everywhere. So far, we have taken 20 truckloads of trash to the dump, and we still have more to go.
Once we finished clearing what we could by hand (to unearth any hidden piles of metal), we used the tractor to clear out our orchard. Still, it was slow going, and we were able to borrow the tractor only every once in a while. Luckily, a kind gentleman who knows my family volunteered to bring his bulldozer up and clear our field of blackberries and thistles. In the space of three days, he cleared and smoothed probably three acres' worth of land.
Fencing the garden
With our field cleared, it was time to set up a garden. We wanted one that was a manageable size for this first year, so we settled on a 15×30-foot space. We had salvaged six 10-foot 4x4s from one of the trash piles, so we used those as posts, dug 3½ feet into the ground. I constructed a simple door out of 2x4s.
With our posts in place, all we needed was fencing. I waited until we saved up enough money, then went down to the local feed store and ordered 800 feet of 2×4-inch welded wire fencing (for future fencing projects) to keep out deer and smaller critters. The ladies that run the store said it was lucky that I purchased the wire when I did, since the very next day the price went up by $30 per 100-foot roll. At that time, I also bought some U-tacks to secure the fencing.
This was where things started to get hard. I had always taken fences for granted, but I will never make that mistake again. As we started to stretch the first section of fencing (using a come-along, a chain, and a truck), the post started to move. We forgot about bracing the corner. We grabbed some more salvaged wood and quickly made some diagonal braces on both sides of each corner post. In the end, we got the fence up just fine, and we learned a lot along the way.
To amend the garden soil, I added some well-rotted chicken manure with a mulch of wood chips. Wood chips tend to lock up the nitrogen in the soil, so in addition to adding extra nitrogen to the soil, we are also planting beans as a cover crop. After harvesting, we will till the plants into the soil, thus adding even more nitrogen.
The garden was previously a huge field full of thistles and blackberries, so to combat those weeds organically, we purchased a propane weed torch that burns at 500,000 BTUs. It seems to be doing the trick, although we will have to be diligent.
The existing orchard
With the garden fence project fresh in our minds, we approached the 700-foot orchard fence more carefully. We needed this fence to protect our existing fruit trees (three cherries, two apples, a peach, and a nectarine) as well as all the fruit trees we plan on planting in the future. Additionally, this fence will keep our chickens contained while they free-range during the day, which is what BHM writer Jackie Clay-Atkinson does. We decided to use H-braces for the fence corner, so that we wouldn't have any issues with the posts moving.
We used old telephone poles for the orchard fencing, as they are free from the local power company.
My husband and I wanted to get moving on the orchard fence, so we didn't wait for his family's tractor and auger attachment to become available. Instead, we grabbed some post hole diggers ($7 at a garage sale) and set about digging 3½-foot holes about 12 inches in diameter. Once we put the pole in the hole, we filled in the hole with gravel, then topped it with dirt. We have dug only about 15 holes so far, with approximately 35 left to go. But until the auger is available, at least we're making progress.
Even though right now my adventures in homesteading mostly consist of brush clearing and good old manual labor, I know that we are laying down the groundwork for the future. One day, we will have a finished farmhouse, a productive garden, rolling hills of pasture surrounded by sturdy fences, and happy livestock wandering in and out of their barn. It's going to take a while to get there, but we're committed to putting in the time, effort, and money in order to fulfill our dream of living a simpler life.
How to butcher a chicken in 20 minutes or less
...while leaving the carcass and feathers intact! By Dr. Roger W. Grim, D.C. Issue #79 • January/February, 2003 Figure 1. With a trash bag properly fitted around...
By Jackie Clay-Atkinson We have had at least one cat in our home ever since I was a young child. So it's no wonder we...
This St. Bernard backwoods hero saved old Grandma's life
Dorper sheep — Revolutionizing the meat sheep industry
Bovine basics for beginners
Raising cattle on your own place
Medical kits for self-reliant families
Better wood heating
Funerals don't have to be expensive
Shearing, carding, spinning, weaving and creating with Margaret Boos
Graft Your Own Designer Fruit Trees
By Jackie Clay Issue #121 • January/February, 2010 Although I've been homesteading for more than forty years, there's always something new to learn. (I figure that if I don't learn at least one thing every day,...
Plant Once Harvest for Years
By Jackie Clay-Atkinson Issue #140 • March/April, 2013 Year after year we start seeds, till the ground, plant, weed, harvest, then tear it all out at the end of the season. It's a lot of work,...


text:
Similarities between 2013 Yankees and 2009 Mets
The first thought readers will get after reading this headline is how I am knocking the Yankees. It could not be further from the truth. I am actually giving the team credit for its 18-12 start, something that did not seem possible given the amount of injuries the team has had to deal with. It all started with the Derek Jeter broken ankle in the 2012 postseason and continued with the Alex Rodriguez hip surgery. Spring training came and Mark Teixeira hurt his wrist and Curtis Granderson broke his forearm. Add in the recent injuries to Francisco Cervelli, Kevin Youkilis, Joba Chamberlain, David Robertson and Ivan Nova, it is almost unfair to expect the Yankees to continue to win at this pace.
The 2009 New York Mets are a fair comparison, albeit a worst case scenario for the 2013 Yankees. The Mets lost key players early in the season and manager Jerry Manuel said something along the lines of treading water until the big guys get back. The Mets injury woes started later on than the Yankees of this season, as Carlos Delgado was the first to go down in April. Then, the mis-diagonosed hamstring injury to Jose Reyes that was supposed to be day to day. Neither would play a game the rest of the season and Delgado was done dor his career. Carlos Beltran was next, though he would return towards the end of the season. JJ Putz, brought in to upgrade an injury plagued and bad bullpen of 2008, had a major arm operation and was out for the season. In addition, John Maine and Oliver Perez made 15 and 14 starts for the team, respectively. Finally, Johan Santana had bone chips removed ending his season after 25 starts.
Despite a 9-12 April, the 2009 Mets were 28-21 after May. Of course, they would be under .500 after June and July only to completely crumble in the second half of the season. Sounds familiar? The Yankees have gotten help from Vernon Wells, Travis Hafner and Lyle Overbay, while relying on guys like Eduardo Nunez (he is hurt too), Jayson Nix, Shawn Kelly, Adam Warren, Brennan Boesch, Ben Francisco and Chris Nelson. In spite of the Yankees not having an interest in spending a ton of money, it was unexpected to be needing key contributions from the preceding players.
That Mets team used a cast of characters led by Gary Sheffield, Livan Hernandez, Tim Redding, Alex Cora, Cory Sullivan, Jeremy Reed and used players like Ramon Martinez, Wilson Valdez, Anderson Hernandez and Elmer Dessens. The problem for the Mets was the fact their key players never got better. To this point, there seems to be good news involving Granderson and even Rodriguez. Hopefully they can get these players back soon and the Yankees can do what the 2009 Mets could not. And that it tread water until their key players get back. If so, it has to be considered the best job Joe Girardi has done as manager.
Preserved floral arrangements link
I always read your blogs they are really interesting and very useful. Thanks for sharing such a great post.


I just joined the groups and must say it is refreshing that everyone is so willing to help out people who have not been a part of theatre very long.
I come with a question or questions about casters/wagons and how to calculate the load and how many casters are needed.
I'm working on the set of The Addams family. I one (two technically) large set pieces that need to be moveable. Two set of stairs. Both with a total run of 14 feet and total Rise of 8foot 6 iniches.
To move them off stage or course stage I need to make them manageable. For 4-8 Student to move.
So my questions are? Does anyone have any suggestion as a rule of thumb number of casters for something that weighs in the ballpark of 300-500 lbs and is 14 feet Long , 8 foot 6 inches high and about 4 foot wide.
For a simple explanation, google, "Tributary area." There are many links out there that show you how to calculate the load on your platform and how it is distributed to each caster. If it confuses you, hit me back and I will run through it with you.
On another note, please don;t attach casters directly to the lid. Make sure the frame transfers the load from the skin to the caster, or your math will be incorrect and your frame will be less than effective.
Thank you for pointing me in the correct direction. I am still working on this. I guess I need to calculate the psf for this will the assumed weight of 500lb over a 14x4 wagon.
500 lb divided by 56 sqft = 8.92pft2 I think that is correct.
Then figuring out the Tributary area and so on and so forth.
Let me know if I'm barking up the wrong tree here..
Thank you for your help Tracy it has been much appreciated.
Welll we build the stairs. Somewhere in the ballpark of 375lbs each.
After the proper calculations and buying the 3P20PST casters from Access caster, the stairs moved flawlessly.
uploading a vidoe of two of the smallest kids i could find to move it.


Tottenham fear Liverpool have edged ahead of them in the battle for PSG Bosman prospect Adrien Rabiot.
The Mirror says Spurs were heavily into a deal to land the Paris Saint-Germain star in a £20million move. But before his transfer to the Premier League could be sealed, Rabiot's father Michel died a few days before the January window closed.
That's when Rabiot becomes a free agent.
Barcelona and Liverpool have already showed huge interest in the France international, and Arsenal would love to join the queue to grab Rabiot.
It all leaves Spurs fearing another major target will slip through their fingers.


text:
Q: How to only build one directory in a Jenkins multi-branch pipeline job? I have a github repo called multibranch-test with two sub-directories Project1, Project2.
PS C:\Repos\multibranch-test> tree .
Folder PATH listing for volume Windows
Volume serial number is 2085-6D3D
C:\REPOS\MULTIBRANCH-TEST
├───Project1
└───Project2

Each sub-directory has a Jenkinsfile and the code for that project.
In Jenkins I have two multibranch pipeline jobs - one for Project1 and one for Project2. In the configuration for Project1 I don't want a push notification or polling to build Project1 if a commit was pushed in sub-directory for Project2.
So in Project1 I have configured Additional Behaviours:

*

*Advanced clone behaviours: Shallow clone is checked

*Sparse checkout path is set to Project1#

*Polling ignores commits in certain paths

*

*Included Regions: Project1/*

*Excluded Regions: *

*Build Configuration: Script Path: Project1/Jenkinsfile

What is happening is if I push a commit to master in sub-directory Project2, both Project1 and Project2 jobs get built. I only want Project2 to build. Can someone point out what I'm doing wrong?
Jenkinsfiles for both Projects are similar and look like:
#!groovy
node  {
    stage ('checkout') {
        checkout scm
    }

    stage ('build') {
        dir ('Project1') {
            bat 'powershell -Command gci'
            bat 'powershell -Command gci env:'
            bat 'powershell -File .\\Project1.ps1'
        }
    }

A: Default Jenkins behavior is that projects get rebuilt if their repo gets a commit, so your commit in repo generates event for both Jenkins projects and triggers both builds. Take a look on Jenkins docs: https://jenkins.io/doc/book/pipeline/
From Jenkins point of view it's hard to tell if change went into project 1 or 2 - what is immediately visible is "new commit to watched repo".
Simples solution would be to split repo into two separate repos one for each project. Since they are supposed to build separately it shouldn't be a problem.

A: This has been a big hassle for us, but we were able to solve it with some workarounds.
We have a master Jenkins job that's triggered by a GitHub commit hook. It figures out what changed since the last commit, and then triggers other service-specific Jenkins jobs.
We have some other conventions we're using (like naming conventions for services, directories, and Jenkins jobs) that aren't specified here, but hopefully this will help someone out.
Here's a breakdown of each component in the solution:

*

*Jenkins jobs and corresponding Jenkinsfiles for each service in the monorepo.

C:\REPOS\MULTIBRANCH-TEST\Project1\Jenkinsfile (your build logic here)
C:\REPOS\MULTIBRANCH-TEST\Project2\Jenkinsfile (your build logic here)

*A shell script, that gets a list of what changed since the last commit (adapted from this blog post).

C:\REPOS\MULTIBRANCH-TEST\change-sets.sh
    #!/usr/bin/env bash

    changeSets=(`git diff-tree --name-status HEAD`)
    for(( i=0; i<${#changeSets[@]}; i++))
    do
      if [ ${changeSets[$i]} == "M" ]
      then
        echo ${changeSets[$i+1]}
      fi
    done

*A Jenkins job that builds on GitHub commit hook

C:\REPOS\MULTIBRANCH-TEST\Jenkinsfile
    #!/usr/bin/env groovy

    pipeline {
        agent any

        stages {

            stage('Define Services to Build') {
                steps {
                    script {

                        def SERVICES_TO_BUILD = sh script:"./change-sets.sh", returnStdout: true
                        SERVICES_TO_BUILD.split("\n").each {
                            echo "Triggering build for ${it}"
                            try {
                                build job: "${it}", propagate: false, wait: false
                            } catch (ex) {
                                echo "Failed to trigger build for ${it}: ${ex.message}"
                            }

                        }
                    }
                }
            }
        }
    }

A: You could create a job for the whole repo, which looks at the changes the commits brought you and then trigger the corresponding Jenkinsfile of project 1 or 2 or both

redpajama_set_name: RedPajamaStackExchange


Featuring original art for purchase by Turk Pipkin and Darden Smith.
Come for the art, stay for readings from both artists' new books. Enjoy music, drinks, and framed art courtesy of Wexel Art.
Limited availability, must RSVP to attend!


Just give her all the Academy Awards.
Hide your tombs, everybody. Alicia Vikander is about to raid them.
The actress already has an Oscar for her performance in "The Danish Girl," so she'll be after different, more ancient hardware in the upcoming "Tomb Raider" film.
News that Vikander would replace Angelina Jolie as the protagonist in the franchise surfaced last year, and now we finally have a look at her in action.
There she is, peeps. Even Angelina is excited.
"For me, it's like 'Raiders of the Lost Ark' meets a genre version of the Joseph Conrad novel Victory: An Island Tale," Goggins told Yahoo.
If "Tomb Raider" is our new "Raiders of the Lost Ark," that makes Vikander our new Indiana Jones.
The new "Tomb Raider" is expected to hit theaters in 2018.


A sleek and slim, shock absorbent snap-on case with card pockets. Each piece is crafted from a custom billboard and protects your iPhone 6/6s Plus while complementing its design. Keep your iPhone safe while using the slots for ID, credit cards, or extra cash. Perfect for people who like to travel light.


We offer CNC precision machining, milling and turning. As well a working to conventional drawings, we are able to work with DXF, IGES and PDF files, sent either by e-mail or supplied on disc. We work with a variety of materials including steel, aluminium, brass, copper, plastic, and exotics, such as titanium & duplex, Stellite 6. Our strength is our experience of working with different materials in many diverse industries. We also source welding, fabrication, and finishing which enables us to offer a complete service to you, the customer.
Browse our Web site for more information about Sevtek Engineering Services. If you have any questions or would like to speak with a Sevtek Engineering Services representative, please e-mail us at owencooper@sevtek.co.uk or call us at 01452 730457.


UIC – International railway union (in French "Union Internationale des Chemins de fer", in English "International Union of Railways") is a global company, which coordinates the development and operation of railway transport in all member countries. It also solves the issues of creating new and maintaining current international connections, the unification of railway equipment. It supervises safety criteria such as interlocking plant and automatic brakes. It represents member companies at the international level.
Entries shown from 10 to 20 out of a total of 752 entries.


The team here at Argrennan is committed to making your special day perfect in every way.
Each wedding is as unique and individual as you are. From an intimate gathering to a large, lavish and lively family wedding, Argrennan can cater for up to 60 guests in the luxurious ceremony room of the Manor House, and up to 200 guests within the tailored greens of the estate in a grand marquee, exclusively for your day and set amidst the spectacular panorama of the Kirkcudbrightshire countryside.
Whatever it takes to make your Wedding Day special to you, Argrennan will ensure it is perfect in every detail with experienced and thoughtful wedding planners to bring the event together in a seamless way. Our bespoke service is designed to offer complete choice and individuality to every wedding couple, making sure every wedding is unique and personal.
Planning your day can be daunting, so we are pleased to offer as much, or indeed as little, involvement as you require to make the first day of the rest of your lives together, perfect from start to finish.
Exclusively yours for your special day. We want you and your guests to feel completely at home when you drive through the gates of the Argrennan estate, into the beauty of our grounds and ultimately to the stunning Manor House with its neoclassical architecture.
Elegance of a bygone era balances with the best of modern standards providing a perfect backdrop to personalise as you wish.
How many day guests will be attending?
How many evening guests will be attending?
Thank you for helping to make our ruby wedding celebration so special. The day was enjoyed by one and all and your slick organisation and attention to detail contributed to making it one to remember. Our thanks once again.


Enduro Tyre featuring fully reinforced radial construction with polyester carcass optimized for high performance. Aggressive tread pattern designed specifically for on and off road utilization, as well as for high mileage service.
Enduro Tyre featuring fully reinforced radial construction with polyester carcass optimized for high performance. Aggressive tread pattern designed specifically for on and off road utilization, as well as for high mileage service. Superior grip both on dry and wet surfaces, obtained through silica enriched compound technology.
Visit our Anlas page to view the full range of Capra tyres.
• High-rigidity Kevlar reinforced casing incorporating a unique 10 mm circumference tie bar ensures excellent stability and rider feedback.
• Designed for tough South African conditions.
• Wide 5:4 chamfer block dual sport tread pattern delivers optimal performance across a broad range of surfaces.
• Excellent grip and traction off and on road, including wet tar..
• High cornering stability , enhanced high speed tracking with low noise and smooth rolling characteristics.
• Good self-cleaning properties for mud and clay conditions.
• Speed ratings from 160-190 km/h.
• Certified to both ECE and DOT international safety specifications.
The nature of dual sport Adventure motorcycles requires consideration as to the type of tyre that best suits your riding preferences. Understanding the construction of bike tyres is a good starting point.


text:
201903 Lead,Malaga Costa del Sol,Estepona,news spain,newspaper,stabbing,The Olive Press /g,">").replace(n,t.Em.replacer);return o="
Home Lead BREAKING: Manhunt after teen stabbed to death 'by foreign attackers' in shopping...
BREAKING: Manhunt after teen stabbed to death 'by foreign attackers' in shopping centre car park on Spain's Costa del Sol – what we know so far
Laurence Dollimore
18 Nov, 2020 @ 17:29
Additional reporting at the scene by Laurence Crumbie and Kirsty McKenzie
A TEENAGER has been stabbed to death in the parking lot of the Diana park shopping centre in Estepona.
The 19-year-old was stabbed in the chest at around 2:30pm today, according to the 112 Emergency service.
The young man was in the car park when a car reportedly pulled up next to him.
SCENE: Police secure sight of fatal stabbing in Diana Park area of Estepona (COPYRIGHT: Olive Press)
Two people jumped out, stabbed him in the chest and hurried back into the vehicle and fled.
According to witnesses, the car was a white Mercedes, which police are desperately trying to track down.
However onlookers have given varying accounts, with one telling police there was a brawl first while others insisted it was a 'foreign light-haired' couple who carried out a premeditated and rapid attack.
Another said it was definitely two men.
The victim was left laying on the asphalt as medics rushed to the scene, but they could not revive him.
Paramedics left at around 4pm as the judicial funeral service arrived to collect the body.
TRAGIC: Body of teenager being taken away by local funeral van (COPYRIGHT: Olive Press)
Policia Nacional are heading up the investigation.
Police are currently at the scene with investigations ongoing. Witnesses have suggested that CCTV captured the violent attack on camera.
A local shopkeeper who was inside her store at the time of the incident said: "It was just after the bus pulled up with the kids from school and a car drove by and a guy got out and stabbed him. He passed away. It's a mess."
An eyewitness told the Olive Press: "He was killed directly in front of his home. He was Latin American. It's such a difficult situation."
Groups of people, both young and old, have now gathered at the site of the tragic killing to mourn the loss of the teenager.
Do you know more about this story? Contact newsdesk@theolivepress.es
news spain
The Olive Press
Previous articleEXCLUSIVE: Teenager killed in deadly drive-by stabbing in Estepona, Malaga
Next articleSenior students to mask up as more cases surface at Gibraltar schools
Laurence has a BA and MA in International Relations and a Gold Standard diploma in Multi-Media journalism from News Associates in London. He was news editor for all print editions of the Olive Press from 2016 to 2019 taking on the role of Digital Editor between January 2020 and February 2021. GOT A STORY? Contact newsdesk@theolivepress.es or call +34 951 273 575 Twitter: @olivepress
Protests break out after Spain's latest gender-based violence saw a woman allegedly killed by her husband in La Linea murder-suicide
Elderly woman on Spain's Costa Blanca defrauded in contactless payment scam
2 bedroom Semi-detached Villa for sale in Alfaz del Pi / L'Alfas del Pi with pool – € 269,000
Woman in Spain's Valencia tricked out of €30,000 by online romance scam
Gibraltar government calls out to artists who would like to have their own studio space
Police confirm terror suspect that killed Algeciras priest first landed in Gibraltar in 2019


text:
Extinction Rebellion postpones Heathrow drone protest plan
FILE – In this Thursday, April 25, 2019 file photo, Extinction Rebellion climate change protesters hold up a banner near the Bank of England, in the City of London. The environmental activist group Extinction Rebellion has postponed a plan to shut down London's Heathrow Airport with drones after it was criticized by politicians and police. The anti-climate change group said Sunday, June 16 it would "not be carrying out any actions at Heathrow Airport in June or July." (AP Photo/Matt Dunham, file)
LONDON (AP) — The environmental activist group Extinction Rebellion has postponed a plan to shut down London's Heathrow Airport with drones after it was criticized by politicians and police.
The group that demands faster action against climate change said Sunday it would "not be carrying out any actions at Heathrow Airport in June or July this year."
Details of the group's plan were leaked last month. British Aviation Minister Charlotte Vere warned that "using drones to deliberately put people's safety at risk carries a maximum life sentence."
Extinction Rebellion said the allegation it was willing to endanger people's lives "is a depressing and predictable smear."
The group still aims to target the airport, Europe's busiest, but said it would not fly drones within flightpaths, and would give two months' notice so travelers could make other plans.
More Business Stories
by KEN SWEET, Associated Press / Jul 19, 2019
NEW YORK (AP) — American Express posted a 9% gain in second-quarter profits on Friday, helped by more of its cardmembers carrying a credit card balance and increased spending on its namesake cards.
The New York company said it earned a profit of $1.76 billion, or $2.07 a share. That's up from earnings of $1.62 billion, or $1.84 a share, in the same period a year earlier. Analysts were looking for AmEx to earn $2.03 a share, according to FactSet.
SOFIA, Bulgaria (AP) — Bulgaria's parliament has approved the purchase of eight new American fighter jets as part of a plan to replace the Balkan country's aging Soviet-built jets and to bring its air force in line with NATO standards.
Lawmakers voted 123-78 on Friday in favor of a government motion to buy the eight F-16 Block 70 aircraft, which will be the biggest military procurement in post-Communist Bulgaria. Two legislators abstained from the vote.
NEW YORK (AP) — American Express is reporting a profit hike of more than 8% from the second-quarter.
The company on Friday posted net income of $1.76 billion, or $2.07. That's a 2-cent beat on Wall Street projections, according to a survey by Zacks Investment Research.
Wednesday night shooting sends felon with violent history back to jail


Poly-twill fabric bag printed with Jürgen Scholz's kitten artwork. Top zip, multiple pockets, dual handles and rhinestone paw print heart charm.
No one captures the charming character of kittens quite like award-winning artist Jürgen Scholz. Now, his celebrated art graces our Smitten with Kittens Tote Bag, exclusively from The Bradford Exchange. Beautifully crafted in printed blue poly-twill fabric featuring curious kittens playing with balls of yarn, it shares the sentiment "Cats leave paw prints on our hearts". A silver-toned heart charm with glittering rhinestones in the shape of a paw print dangles from the front handle.
This fashion-savvy women's shoulder tote is loaded with purr-sonality and sure to melt hearts wherever you go, but it's just as practical as it is pretty. While its top zip closure keeps all your belongings secure, it also keeps them organized with two large side pockets, a centered zip compartment, one inside zippered pocket and two slip pockets. Dual handles and silver-toned hardware add chic finishing touches. This cat-themed accessory is sure to delight stylish fans of Jürgen Scholz and anyone smitten with kittens, and high demand is expected. Don't wait, order now!
Beautifully crafted of printed blue poly-twill fabric, this stylish women's shoulder tote showcases Mr. Scholz's imagery of curious kittens playing with balls of yarn, recreated in vivid color and detail. Imported.
The charming artwork is highlighted by the sentiment "Cats leave paw prints on our hearts"
Smitten with Kittens Tote Bag with Jurgen Scholz artwork! Women's shoulder tote is the purr-fect cat-themed accessory!