Hello, my partner! Let's explore the mining machine together!

[email protected]

magnetic separator promega

epigenetic silencing by setdb1 suppresses tumour intrinsic immunogenicity | nature

epigenetic silencing by setdb1 suppresses tumour intrinsic immunogenicity | nature

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Epigenetic dysregulation is a defining feature of tumorigenesis that is implicated in immune escape1,2. Here, to identify factors that modulate the immune sensitivity of cancer cells, we performed in vivo CRISPRCas9 screens targeting 936 chromatin regulators in mouse tumour models treated with immune checkpoint blockade. We identified the H3K9 methyltransferase SETDB1 and other members of the HUSH and KAP1 complexes as mediators of immune escape3,4,5. We also found that amplification of SETDB1 (1q21.3) in human tumours is associated with immune exclusion and resistance to immune checkpoint blockade. SETDB1 represses broad domains, primarily within the open genome compartment. These domains are enriched for transposable elements (TEs) and immune clusters associated with segmental duplication events, a central mechanism of genome evolution6. SETDB1 loss derepresses latent TE-derived regulatory elements, immunostimulatory genes, and TE-encoded retroviral antigens in these regions, and triggers TE-specific cytotoxic T cell responses in vivo. Our study establishes SETDB1 as an epigenetic checkpoint that suppresses tumour-intrinsic immunogenicity, and thus represents a candidate target for immunotherapy.

All genomic sequencing data that support the findings of this study have been deposited in the Gene Expression Omnibus database with the accession code GSE155972. The original mass spectra for all experiments, and the protein sequence database used for searches have been deposited in the public proteomics repository MassIVE (https://massive.ucsd.edu) and are accessible at ftp://massive.ucsd.edu/MSV000086580/.Source data are provided with this paper.

Takahashi, Y. et al. Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells. J. Clin. Invest. 118, 10991109 (2008).

White, H. D., Roeder, D. A. & Green, W. R. An immunodominant Kb-restricted peptide from the p15E transmembrane protein of endogenous ecotropic murine leukemia virus (MuLV) AKR623 that restores susceptibility of a tumor line to anti-AKR/Gross MuLV cytotoxic T lymphocytes. J. Virol. 68, 897904 (1994).

D, L., Lauren, D., Van, P., Bradley, E. & Charles, B. Mint-ChIP3: A low-input ChIP-seq protocol using multiplexed chromatin and T7 amplification v1. protocols.io https://doi.org/10.17504/protocols.io.wbefaje (2019).

Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 12131218 (2013).

Mi, H., Muruganujan, A., Ebert, D., Huang, X. & Thomas, P. D. PANTHER version 14: more genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res. 47 (D1), D419D426 (2019).

Evans, L. H., Morrison, R. P., Malik, F. G., Portis, J. & Britt, W. J. A neutralizable epitope common to the envelope glycoproteins of ecotropic, polytropic, xenotropic, and amphotropic murine leukemia viruses. J. Virol. 64, 61766183 (1990).

Mertins, P. et al. Reproducible workflow for multiplexed deep-scale proteome and phosphoproteome analysis of tumor tissues by liquid chromatography-mass spectrometry. Nat. Protoc. 13, 16321661 (2018).

Reynisson, B., Alvarez, B., Paul, S., Peters, B. & Nielsen, M. NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data. Nucleic Acids Res. 48 (W1), W449W454 (2020).

This work was supported by funds from Calico Life Sciences, the Gene Regulation Observatory at the Broad Institute of MIT and Harvard, the Damon-Runyon Cancer Research Foundation (to G.K.G. and J.W.), the National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (NIH/NCI U24-CA210986 and NIH/NCI U01 CA214125 to S.A.C), the Wong Family Award (to B.C.M.), and the NCI/NIH Directors Fund (DP1CA216873 to B.E.B.). B.E.B. is the Bernard and Mildred Kayden Endowed MGH Research Institute Chair and an American Cancer Society Research Professor. The authors thank all members of the Bernstein and Manguso laboratories at MGH and the Broad Institute, E. Van Allen, N. Vokes, A. Sharpe, G. Poncet-Montange, D. McKinney, T. Sundberg, J. Growney, D. Stokoe and A. Firestone for thoughtful discussions and feedback. Graphics in Fig. 1a were created with Biorender.com using a paid license.

Gabriel K. Griffin,Jingyi Wu,Arvin Iracheta-Vellve,James C. Patti,Jeffrey Hsu,Thomas Davis,Deborah Dele-Oni,Peter P. Du,Aya G. Halawi,Sarah Y. Kim,Susan Klaeger,Nelson H. Knudsen,Brian C. Miller,Tung H. Nguyen,Kira E. Olander,Malvina Papanastasiou,Suzanna Rachimi,Emily J. Robitschek,Emily M. Schneider,Mitchell D. Yeary,Margaret D. Zimmer,Jacob D. Jaffe,Steven A. Carr,John G. Doench,W. Nicholas Haining,Kathleen B. Yates,Robert T. Manguso&Bradley E. Bernstein

Conception and experimental design: G.K.G., J.W., A.I.-V., J.G.D., J.D.J., S.A.C., W.N.H., K.B.Y., R.T.M. and B.E.B. Methodology and data acquisition: G.K.G., J.W., A.I.-V., J.C.P., J.H., D.D.-O., A.H., S.K., N.H.K., B.C.M., T.H.N., K.E.O., M.P., S.R., E.J.R., E.M.S., M.D.Y., M.D.Z., J.D.J., K.B.Y., R.T.M. and B.E.B. Analysis and interpretation of data: G.K.G., J.W., A.I.-V., J.C.P., J.H., T.D., D.D.-O., A.G.H., P.P.D., J.J.I., S.Y.K., S.K., N.H.K., B.C.M., T.H.N., K.E.O., M.P., S.R., E.J.R., M.D.Y., M.D.Z., J.D.J., W.N.H., K.B.Y., R.T.M. and B.E.B. Manuscript writing and revision: G.K.G., K.B.Y., R.T.M. and B.E.B. In addition to the equally contributing first authors, co-authors J.C.P., J.H. and T.D. each made critical and equal contributions to experimental and computational aspects of this study.

G.K.G. consults for Moderna Therapeutics. J.J.I. consults for Tango Therapeutics and Phenomic AI. B.C.M. consults for Rheos Medicines. J.G.D. consults for Agios, Foghorn Therapeutics, Maze Therapeutics, Merck and Pfizer; J.G.D. consults for and has equity in Tango Therapeutics. S.C.A. is a member of the scientific advisory boards of Kymera, PTM BioLabs and Seer and an ad hoc scientific advisor to Pfizer and Biogen. R.T.M. consults for Bristol Myers Squibb. B.E.B. declares outside interests in Fulcrum Therapeutics, Arsenal Biosciences, HiFiBio, Cell Signaling Technologies and Chroma Medicine. The remaining authors declare no competing interests.

a, Tumour volumes (mean s.e.m.) of bilateral tumours (n=25 mice, n=50 individual tumours) in the LLC (top) and B16 (bottom) screens for the indicated treatment conditions on day 12 (LLC) and day 9 (B16) after tumour inoculation. Statistics by ANOVA with Tukeys test for multiple comparisons. b, Saturation analysis of animal replicates from the three in vivo screening conditions for LLC (top) and B16 (bottom). Pearsons correlations are calculated for the log2 guide abundance in one animal versus any other animal, then for two averaged animals versus any other two, and so on. Saturation approaches r=0.95 for both screens. c, Depletion (negative ratios) or enrichment (positive ratios) of targeted chromatin regulator genes in ICB-treated WT versus NSG mice in the LLC (x-axis) and B16 (y-axis) screens. Circle sizes reflect the significance (log10(P value)) of depletion in the higher scoring model. Selected genes that scored uniquely in B16 (left) or LLC (right) are highlighted and coloured according to their associated chromatin regulator complexes. d,RNA expression (FPKM) in LLC (x-axis) and B16 (y-axis) for the top 30 screening hits by STARS score in each cell line. Colours indicate whether the gene was depleted in LLC only (orange), B16 only (blue), or in both cell lines (red). One outlier value (x = 11.7, y = 248.7) for the B16-only hit, Cdk2 is excluded for ease of visualization but is included in the calculation of the correlation coefficient. *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001.

a, Tumour growth (mean s.e.m.) in untreated WT mice (no ICB) inoculated with Setdb1 (n=10) Tasor (n=5), Mphosph8 (n=5), or Trim28 (n=5) KO LLC cells, or Setdb1 or Trim28 KO B16 cells. Data are representative of 3 (Setdb1), 1 (Tasor), 1 (Mphosph8), 1 (Trim28 in LLC), and 2 (Trim28 in B16) experiments. Statistics by two-sided Students t-test at the indicated time-points. b, Tumour growth (mean s.e.m.) in WT mice treated with ICB inoculated with Mphosph8 (n=20) or Trim28 (n=20) KO LLC cells. Data represent 1 experiment. Statistics by two-sided Students t-test at the indicated time-points. c, Overall survival for untreated (top) and ICB-treated (bottom) WT mice inoculated with B16 (left) or LLC (right) tumours and corresponding to Fig. 1d. Statistics by log-rank test. d, Tumour growth (top, mean s.e.m.) and overall survival (bottom) for untreated NSG mice (no ICB) inoculated with Setdb1 KO B16 (left, n=20) or LLC (right, n=15). Data represent 1 experiment. Statistics for tumour growth by two-sided Students t-test at the indicated time-points. Statistics for overall survival by log-rank test. *P<0.05; ***P<0.001; ****P<0.0001.

a, Running enrichment scores by GSEA for immune gene sets significantly (FDR <0.001) anti-correlated with SETDB1 expression by Pearsons correlation across TCGA cohorts. b, Pearsons correlation between SETDB1 expression and cytolytic score (geometric mean of PRF1 and GZMA expression) in TCGA cohorts. Circle size indicates statistical significance (log10(P value)) of the Pearsons correlation. Blue and red indicate negative and positive values, respectively.c, Bootstrap analysis plotting the rank of the correlation between cytolytic score and SETDB1 expression (red lines) in each TCGA cohort, compared to 408 randomly selected control genes (grey lines). d, KaplanMeier curves for patients with renal cell carcinoma treated with PD-1 blockade (left, nivolumab) or mTOR inhibitor (right, everolimus). Overall survival curves are stratified according to SETDB1 expression (top 50%, high expression; bottom 50%, low expression). Hazard ratios associated with SETDB1 high expression are listed. The number of patients-at-risk are indicated for each time point. Statistics by log-rank test. e, Bootstrap analysis showing the impact of GISTIC2-defined copy-number alterations (CNA) on overall survival in patients treated with mTOR inhibitor (left, everolimus) or PD-1 blockade (right, nivolumab). Positive values indicate a CNA that has a harmful impact on survival with ICB or mTOR inhibitor, and negative values indicate a CNA that has a beneficial effect. 1q21.3 amplification (red) is highlighted alongside chromosomal regions previously reported as predictors of ICB response in RCC, including 10q23.31 deletion (associated with improved response) and 9p21.3 deletion (associated with poor response).

a, Heat map of H3K9me3 peaks (rows, FPKM) in control and Setdb1 KO LLC (left) and B16 (right) cells. Peaks are separated based on whether they were lost (top) or retained (bottom) in Setdb1 KO cells, and annotated by whether they are located in the open compartment A of the genome. Statistics for compartment A enrichment by permutation testing. b, The number of 100-kb windows containing the indicated numbers of SETDB1-dependent H3K9me3 peaks in B16 (left) or LLC (right) cells, compared to random control peaks. Statistics by Chi-square test. c, Workflow for annotation of SETDB1-domains from H3K9me3 ChIPseq data in LLC and B16 cells. *P<0.05; ****P<0.0001.

a, Proportion of chromatin accessible sites (ATAC-seq) gained in Setdb1 KO LLC or B16 cells that are located within (red) or outside (grey) SETDB1 domains. b, Proportion of ATAC-seq sites gained in Setdb1 KO LLC or B16 cells that coincide with promoters (light grey), distal TEs (red), or other promoter-distal sites (dark grey). Statistics by permutation testing. c, Proportion of gained ATAC-seq sites at distal TEs in Setdb1 KO B16 cells that also gain H3K27 acetylation and resemble active enhancers. d, Coordinate gain of chromatin accessibility and H3K27 acetylation at an example TE-site in Setdb1 KO B16 cells. e, Activation of genes near (<50 kb) gained ATAC-seq sites at distal TEs in Setdb1 KO LLC or B16 cells compared to control genes. Statistics by permutation testing. fg, Flow cytometry in control and Setdb1 KO cells showing gating strategy (f), cell-surface expression (g) (y-axis, median fluorescence intensity (MFI)) for ULBP1 and RAET1 ligands in LLC (left), and MHCI expression in LLC and B16 (right) with or without induction with IFN (10 ngml1, 24 h). Data are mean s.e.m. and reflect 2 independent experiments with 4 biological replicates. Statistics by two-sided Students t-test. *P<0.05; **P<0.01.

a, Distribution of TE types (top) and LTR subfamilies (bottom) induced in Setdb1 KO LLC or B16 cells by RNA-seq. b, Heat map showing RNA expression (row normalized) of canonical interferon-stimulated genes in untreated and poly(I:C) stimulated (500 ngml1, 48h) control and Setdb1 KO LLC and B16 cells. c, Percentage of TEs induced in Setdb1 KO LLC or B16 cells that retain intact viral ORFs, compared to control TEs. Statistics by Fishers exact test. d, Flow cytometry for cell-surface expression of the MuLV envelope protein in Setdb1 KO LLC and B16 cells. Gating strategy (left) and histograms (right) with mode-normalized cell counts are shown. Data are representative of n=3 and n=2 experiments in LLC and B16, respectively. e, Differential protein expression in B16 cells by whole-cell mass spectrometry. Tryptic protein sequences derived from TEs (red) or canonical proteins (grey) are highlighted. Fold-change (x-axis) and statistical significance (y-axis) for proteins in Setdb1 KO versus control are shown. f, Venn diagrams showing the number of predicted, unique TE-encoded H2-Kb/H2-Db binding peptides in LLC and B16 cells by GRCm38 RNA-seq analysis. Diagrams show the total number of predicted, TE-encoded MHC Class I peptides in LLC and B16 cells (left), and subsets showing (1) high expression in control cells and further induction upon Setdb1 KO (middle), and (2) no detectable expression in control cells and strong induction only upon Setdb1 KO (right). Several MuLV-encoded peptides known to be presented by H2-Kb or H2-Db are highlighted. ***P<0.001. ****P<0.0001.

a, Distribution of TE types (top) and LTR subfamilies (bottom) induced in SETDB1 KO A375 cells by RNA-seq. b, Volcano plot of Hallmark IFN-alpha response genes in A375 cells by RNA-seq. Fold-change (x-axis) and statistical significance (y-axis) in SETDB1 KO versus control are shown. c, Percentage of TEs induced in Setdb1 KO A375 cells that retain intact viral ORFs compared to control TEs. Statistics by Fishers exact test. d, Diagram showing the total number of predicted, unique TE-encoded MHCI peptides induced in SETDB1 KO A375 cells by RNA-seq. Binding predictions are based on A375-specific HLA types (seeMethods). Subsets of predicted TE-encoded MHCI peptides with (1) high expression in control cells and further induction upon SETDB1 KO, or (2) no detectable expression in control cells and strong induction only upon SETDB1 KO, are highlighted. ***P<0.001. ****P<0.0001.

ac, Transcriptional profiling with RNA-seq performed on bulk tumour tissue from control (n=8 untreated and n=6 ICB-treated) and Setdb1 KO (n=10 untreated and n=6 ICB-treated) LLC tumours. Data represent 1 experiment. a, Running enrichment scores by GSEA for immune gene sets significantly (FDR <0.01) upregulated in Setdb1 KO LLC tumours treated with ICB relative to controls. b, Volcano plot depicts expression fold-change (x-axis) and statistical significance (y-axis) of cytotoxicity genes (red) and all other genes (grey) in Setdb1 KO LLC tumours treated with ICB relative to controls. c, TCR repertoire profiling with targeted sequencing of alpha and beta-chain variable regions from Setdb1 KO LLC tumours (untreated and ICB-treated) relative to controls. Variation in clonotype abundance (skewing) is represented by the Gini index (left, higher number indicates greater skewness) and Shannon entropy (right, lower number indicates greater skewness). Data are mean s.e.m. Statistics by two-sided Students t-test. dh, scRNA-seq (3) analysis of immune cells (CD45+ enrichment) from control (n=3 untreated, n=4 ICB-treated) or Setdb1 KO (n=3 untreated, n=4 ICB-treated) LLC tumours. Data are from 1 experiment. d, UMAP plots highlight 4,497 cells and associated clusters identified in the lymphoid compartment. e, Representative marker genes used to identify and annotate cell clusters in d. f, Changes in lymphoid populations in ICB-treated tumours (n=4 control, n=4 Setdb1 KO) as a proportion of the total lymphoid population. Data are mean s.e.m. Statistics by two-sided Students t-test. g, Ratio of NK-2 to NK-1 cells in ICB-treated samples. Data are mean s.e.m. Statistics by MannWhitney U test. h, Differentially expressed genes (log2(fold-change)) in NK-2 vs NK-1 cells. Circle sizes indicate statistical significance (FDR). *P<0.05. ****P<0.0001.

a, Unique CDR3 sequences (x-axis) identified from TCR sequencing of flow-sorted p15E-tetramer-positive CD8+ T cells isolated from control LLC tumours. High-confidence CDR3 sequences (n=377) are highlighted by brackets and identified based on strong statistical enrichment (log10(P value) > 46 cut-off indicated by dotted line, seeMethods) within the p15E-tetramer-positive fraction. b, c, scRNA-seq (5) of 24,860 lymphoid cells (CD4+CD8+ enrichment) isolated from control (n=4 untreated, n=4 ICB-treated) and Setdb1 KO (n=3 untreated, n=3 ICB-treated) LLC tumours. b, UMAP plot highlights cell populations identified among CD4+CD8+-enriched lymphoid cells. c, Representative marker genes used to identify and annotate cell clusters in b. d, Representative flow cytometry gating strategy for p15E-tetramer studies. Corresponds to Fig. 4e. *P<0.05.

a, Overall survival for ICB-treated WT mice inoculated with control and Setdb1 KO B16 (left) or LLC (right) cells with intact (B2m WT) or deficient (B2m KO) MHCI, as detailed in Fig. 4f and Methods. Statistics by log-rank test. b, Overall survival for ICB-treated WT mice inoculated with control or Setdb1 KO B16 (left) or LLC (right) cells that received intraperitoneal injections with isotype (left), CD8-depleting (middle), or NK-depleting (right) antibodies starting on day 3 before tumour challenge and continuing every 3 days until day 18, as detailed in Fig. 4f and Methods. Statistics by log-rank test. *P<0.05; ***P<0.001.

Griffin, G.K., Wu, J., Iracheta-Vellve, A. et al. Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity. Nature 595, 309314 (2021). https://doi.org/10.1038/s41586-021-03520-4

mouse totipotent stem cells captured and maintained through spliceosomal repression - sciencedirect

mouse totipotent stem cells captured and maintained through spliceosomal repression - sciencedirect

Spliceosomal repression reprograms pluripotent mouse ESCs to a totipotent statePlaB enables invitro culture of TBLCs molecularly close to totipotent blastomeresTBLCs have robust bidirectional embryonic and extraembryonic differentiation potentialPluripotent and totipotent genes respond differentially to spliceosomal repression.

Since establishment of the first embryonic stem cells (ESCs), invitro culture of totipotent cells functionally and molecularly comparable with invivo blastomeres with embryonic and extraembryonic developmental potential has been a challenge. Here we report that spliceosomal repression in mouse ESCs drives a pluripotent-to-totipotent state transition. Using the splicing inhibitor pladienolide B, we achieve stable invitro culture of totipotent ESCs comparable at molecular levels with 2- and 4-cell blastomeres, which we call totipotent blastomere-like cells (TBLCs). Mouse chimeric assays combined with single-cell RNA sequencing (scRNA-seq) demonstrate that TBLCs have a robust bidirectional developmental capability to generate multiple embryonic and extraembryonic cell lineages. Mechanically, spliceosomal repression causes widespread splicing inhibition of pluripotent genes, whereas totipotent genes, which contain few short introns, are efficiently spliced and transcriptionally activated. Our study provides a means for capturing and maintaining totipotent stem cells.

magnabot ii magnetic separation device, promega | vwr

magnabot ii magnetic separation device, promega | vwr

So much has changed during this unprecedented time, except your ability to count on Avantor. We continue to set science in motion to create a better world by providing you with the right solutions to keep moving forward.

Our solutions, developed with you as our focus, are crafted by our team and network of professionals with advanced degrees in science, quality control, engineering, manufacturing and industry experience.

VWR is proud of our years of experience providing choice and excellent service to the Industrial market from Food & Beverage, Petrochemical, Environmental Testing, Waste Water, Cosmetics, Consumer Goods, Agriculture and more...

Weve built our reputation on consistent, comprehensive mastery of day-to-day operations, allowing lab, clinical, and production environments to focus their high-value resources on core scientific priorities.

As our customers needs have evolved, so have our capabilities. We have become experts in scientific operations, improving performance with sophisticated solutions and providing guidance on best practices.

We found alternative products that can save you up to per item-unit. To compare product details, select up to 3 alternatives below and click Compare Selected. To add items to your cart, enter a quantity and click Add to Cart.

Avantor, a Fortune 500 company, is a leading global provider of mission-critical products and services to customers in the biopharma, healthcare, education & government, and advanced technologies & applied materials industries. Our portfolio is used in virtually every stage of the most important research, development and production activities in the industries we serve. One of our greatest strengths comes from having a global infrastructure that is strategically located to support the needs of our customers. Our global footprint enables us to serve more than 225,000 customer locations and gives us extensive access to research laboratories and scientists in more than 180 countries. We set science in motion to create a better world. For information visit, www.avantorsciences.com and find us on LinkedIn, Twitter and Facebook.

Thank you for visiting our site. These terms and conditions of use are applicable to the United States, Canada and Puerto Rico websites (collectively the Web Site) operated by VWR (the Company). If you are accessing the Web Site from outside the United States, Canada, or Puerto Rico, please see the appropriate international website, available at www.vwr.com, for applicable terms and conditions. All users of the Web Site are subject to the following website terms and conditions of use (these Terms of Use). Please read these Terms of Use carefully before accessing or using any part of the Web Site. By accessing or using the Web Site, you agree that you have read, understand and agree to be bound by these Terms of Use, as amended from time to time, as well as the Company Privacy Policy, which is hereby incorporated into these Terms of Use. If you do not wish to agree to these Terms of Use, do not access or use any part of the Web Site.

The Company may revise and update these Terms of Use at any time without notice by posting the amended terms to the Web Site. Your continued use of the Web Site means that you accept and agree to the revised Terms of Use. If you disagree with the Terms of Use (as amended from time to time) or are dissatisfied with the Web Site, your sole and exclusive remedy is to discontinue using the Web Site.

The information contained on this Web Site is provided for informational purposes only. Although the information is believed to correct at the time of publishing, you should make your own determination as to its suitability for your use. Not all of the products or services described in this Web Site are available in all jurisdictions or to all potential customers, and nothing herein is intended as an offer or solicitation in any jurisdiction or to any potential customer where such offer or sale is not qualified.

These Terms and Conditions apply only to the use of the Web Site. Please note, the terms and conditions relating to service, product sales, promotions, and other related activities can be found at https://us.vwr.com/store/content/externalContentPage.jsp?path=/en_US/about_vwr_terms_and_conditions.jsp, and those terms and conditions control any purchases of products or services from the Company.

The Web Site may contain bulletin board services, chat areas, news groups, forums, communities, personal web pages, calendars, and/or other message or communication facilities designed to enable you to communicate with the public at large or with a group (collectively, "Community Feature"). You agree to use the Community Feature only to post, send and receive messages and material that are proper and related to the particular Community Feature. You agree to use the Web Site only for lawful purposes.

1. Defame, abuse, harass, stalk, threaten or otherwise violate the legal rights (such as rights of privacy and publicity) of others. 2. Publish, post, upload, distribute or disseminate any inappropriate, profane, defamatory, infringing, obscene, indecent or unlawful topic, name, material or information. 3. Upload files that contain software or other material protected by intellectual property laws (or by rights of privacy of publicity) unless you own or control the rights thereto or have received all necessary consents. 4. Upload files that contain viruses, corrupted files, or any other similar software or programs that may damage the operation of another's computer. 5. Intercept or attempt to intercept electronic mail not intended for you. 6. Advertise or offer to sell or buy any goods or services for any business purpose, unless such Community Feature specifically allows such messages. 7. Conduct or forward surveys, contests, pyramid schemes or chain letters. 8. Download any file posted by another user of a Community Feature that you know, or reasonably should know, cannot be legally distributed in such manner or that you have a contractual obligation to keep confidential (notwithstanding its availability on the Web Site). 9. Falsify or delete any author attributions, legal or other proper notices or proprietary designations or labels of the origin or source of software or other material contained in a file that is uploaded. 10. Misrepresent an affiliation with any person or organization. 11. Engage in any other conduct that restricts or inhibits anyones use of the Web Site, or which, as determined by the Company, may harm the Company or users of the Web Site or expose them to liability. 12. Violate any applicable laws or regulations or violate any code of conduct or other guidelines which may be applicable for any particular Community Feature . 13. Harvest or otherwise collect information about others, including e-mail addresses, without their consent.

B. You understand and acknowledge that you are responsible for whatever content you submit, you, not the Company, have full responsibility for such content, including its legality, reliability and appropriateness. If you post in the name of or on behalf of your employer or another entity, you represent and warrant that you are authorized to do so. By uploading or otherwise transmitting material to any area of the Web Site, you warrant that the material is your own or is in the public domain or otherwise free of proprietary or other restrictions and that you have the right to post it to the Web Site. Additionally, by uploading or otherwise transmitting material to any area of the Web Site you are granting the Company a irrevocable, royalty-free, worldwide right to publish, reproduce, use, adapt, edit and/or modify such material in any way, in any and all media now known or hereafter discovered, worldwide, including on the Internet and World Wide Web, for advertising, commercial, trade and promotional purposes, without additional limitation or compensation, unless prohibited by law, and without notice, review or approval.

C. The Company reserves the right, but does not assume any responsibility, to (1) remove any material posted on the Web Site which the Company, in its sole discretion, deems inconsistent with the foregoing commitments, or otherwise inappropriate for any reason; and (2) terminate any users access to all or part of the Web Site. However, the Company can neither review all material before it is posted on the Web Site nor ensure prompt removal of objectionable material after it has been posted. Accordingly, the Company assumes no liability for any action or inaction regarding transmissions, communications or content provided by third parties. The Company reserves the right to take any action it deems necessary to protect the personal safety of users of this Web Site and the public; however, the Company has no liability or responsibility to anyone for performance or nonperformance of the activities described in this paragraph.

Any content and/or opinions uploaded, expressed or submitted through any Community Feature or any other publicly available section of the Web Site (including password-protected areas), and all articles and responses to questions, other than the content explicitly authorized by the Company, are solely the opinions and responsibility of the person or entity submitting them and do not necessarily reflect the opinions of the Company. By way of example, any recommended or suggested use of products or services available from the Company that is posted through a Community Feature is not a sign of approval or recommendation by the Company. If you choose to follow any such recommendation you do so at your own risk.

The Web Site may contain links to other websites on the internet. The Company is not responsible for the content, products, services or practices of any third party websites, including without limitation sites linked to or from the Web Site, sites framed within the Web Site or third party advertisements, and does not make representations regarding their quality, content or accuracy. The presence of links from the Web Site to any third party website does not mean that we approve of, endorse or recommend that website. We disclaim all warranties, express or implied, as to the accuracy, legality, reliability or validity of any content on any third party website. Your use of third party websites is at your own risk and subject to the terms and conditions of use for such websites.

You acknowledge and agree that the entire contents of the Web Site (including all information, data, software, graphics, text, images, logos, and/or other material) and the design, selection, collection, arrangement and assembly thereof, are proprietary to the Company and are protected by United States and international intellectual property laws. You are authorized only to use the content on the Web Site for personal use or legitimate business purposes. You may not copy, modify, create derivative works of, publicly display or perform, republish, store, transmit, distribute, remove, delete, augment, add to, participate in the transfer of, license or sell any of the material on the Web Site without the prior written consent of the Company, except to: (a) store copies of such materials temporarily in RAM, (b) store files that are automatically cached by your Web browser for display enhancement purposes, and (c) print a reasonable number of pages of a Web Site; provided in each case that you do not alter or remove any copyright or other proprietary notices included in such materials. Neither the title nor any intellectual property rights to any information or material on the Web Site are transferred to you, but remain with the Company or the applicable owner of such content.

The Company name and logo, and all related names, logos, product and service names appearing on the Web Site are trademarks of the Company and/or the applicable third party suppliers. They may not be used or redisplayed without the Companys prior written consent.

The Company does not assume any liability for the materials, information and opinions provided on, or available through, the Web Site (the Site Content). Reliance on the Site Content is solely at your own risk. The Company disclaims any liability for injury or damages resulting from the use of any Site Content. THE WEB SITE, THE SITE CONTENT AND THE PRODUCTS AND SERVICES PROVIDED ON OR AVAILABLE THROUGH THE WEB SITE ARE PROVIDED ON AN AS IS AND AS AVAILABLE BASIS, WITH ALL FAULTS. NEITHER THE COMPANY NOR ANY PERSON ASSOCIATED WITH THE COMPANY MAKES ANY WARRANTY OR REPRESENTATION WITH RESPECT TO THE QUALITY, ACCURACY, OR AVAILABILITY OF THE WEB SITE. SPECIFICALLY, BUT WITHOUT LIMITING THE FOREGOING, NEITHER THE COMPANY NOR ANYONE ASSOCIATED WITH THE COMPANY WARRANTS OR REPRESENTS THAT THE WEB SITE, THE SITE CONTENT OR THE SERVICES PROVIDED ON OR THROUGH THE WEB SITE WILL BE ACCURATE, RELIABLE, ERROR-FREE OR UNINTERRUPTED; THAT DEFECTS WILL BE CORRECTED; THAT THE WEB SITE OR THE SERVER THAT MAKES IT AVAILABLE ARE FREE OF VIRUSES OR OTHER HARMFUL COMPONENTS; OR THAT THE WEB SITE WILL OTHERWISE MEET YOUR NEEDS OR EXPECTATIONS. THE COMPANY DISCLAIMS ALL WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING ANY WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NON-INFRINGEMENT. IN NO EVENT WILL THE COMPANY OR ITS LICENSORS OR CONTRACTORS BE LIABLE FOR ANY DAMAGES OF ANY KIND, UNDER ANY LEGAL THEORY, ARISING OUT OF OR IN CONNECTION WITH YOUR USE OF, OR INABILITY TO USE, THE WEB SITE, THE SITE CONTENT, ANY SERVICES PROVIDED ON OR THROUGH THE WEB SITE OR ANY LINKED SITE, INCLUDING ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, CONSEQUENTIAL OR PUNITIVE DAMAGES, INCLUDING, BUT NOT LIMITED TO, PERSONAL INJURY, LOST PROFITS OR DAMAGES RESULTING FROM DELAY, INTERRUPTION IN SERVICE, VIRUSES, DELETION OF FILES OR ELECTRONIC COMMUNICATIONS, OR ERRORS, OMISSIONS OR OTHER INACCURACIES IN THE WEB SITE OR THE SITE CONTENT OR SERVICES, WHETHER OR NOT THERE IS NEGLIGENCE BY THE COMPANY AND WHETHER OR NOT THE COMPANY HAS BEEN ADVISED OF THE POSSIBILITY OF ANY SUCH DAMAGES, UNLESS PROHIBITED BY APPLICABLE LAW.

You agree to indemnify and hold harmless the Company and its officers, directors, agents, employees, and others involved in the Web Site, from and against any and all liabilities, expenses, damages and costs, including reasonable attorneys fees, arising from any violation by you of these Terms and Conditions of Use, your use of the Web Site or any products, services or information obtained from or through the Web Site, your connection to the Web Site, any content you submit on the Web Site through any Community Feature , or your violation of any rights of another.

These terms will be governed by and construed in accordance with the laws of the State of Pennsylvania, without regard to any principles of conflicts of law. You agree that any action at law or in equity that arises out of or relates to these Terms and Conditions of Use will be filed exclusively in the state or federal courts located in Pennsylvania and you hereby consent and submit to the personal jurisdiction of such courts for the purposes of litigating any such action. These Terms and Conditions of Use are applicable to users in the United States, Canada, and Puerto Rico. If you are accessing the Web Site from outside the United States, Canada, or Puerto Rico, please see the appropriate international website, available at www.vwr.com, for applicable terms and conditions. If you elect to access this Web Site from outside of the specified jurisdictions rather than use the available international sites, you agree to these Terms and Conditions of Use and that such terms will be governed and construed with the laws of the United States and the State of Pennsylvania and that we make no representation that the materials or services on this Web Site are appropriate or available for use in those other jurisdictions. In any event, all users are responsible for their own compliance with local laws.

These Terms and Conditions of Use, as they may be amended from time to time, constitute the entire agreement and understanding between you and us governing your use of the Web Site. Our failure to exercise or enforce any right or provision of the Terms and Conditions of Use shall not constitute a waiver of such right or provision. If any provision of the Terms and Conditions of Use is found by a court of competent jurisdiction to be invalid, you nevertheless agree that the court should endeavor to give effect to the parties' intentions as reflected in the provision, and the other provisions of the Terms and Conditions of Use shall remain in full force and effect. Neither a course of dealing or conduct between you and the Company nor any trade practices shall be deemed to modify these Terms and Conditions of Use. You agree that regardless of any statute or law to the contrary, any claim or cause of action arising out of or related to use of the Site or the Terms and Conditions of Use must be filed within one (1) year after such claim or cause of action arose or be forever barred. Any rights not expressly granted herein are reserved by and for the Company. We may terminate your access, or suspend any user's access to all or part of the Site, without notice, for any conduct that we, in our sole discretion, believe is in violation of any applicable law or is harmful to the interests of another user, a third-party provider, a service provider, or us. Any inquiries concerning these Terms and Conditions of Use should be directed to [email protected]

We respect the intellectual property of others, and we ask our users to do the same. If you believe that your work has been copied and is accessible on the Site in a way that constitutes copyright infringement, you may notify us by providing our copyright agent the following information:

magnabot flat top magnetic separation device

magnabot flat top magnetic separation device

If you are located in the EEA, the United Kingdom, or Switzerland, you can change your settings at any time by clicking Manage Cookie Consent in the footer of our website.

Our website does not fully support your browser. We've detected that you are using an older version of Internet Explorer. Your commerce experience may be limited. Please update your browser to Internet Explorer 11 or above. Dismiss

cookiescookiescookiescookiescookiescookies

magnabot flex 96 magnetic separation device

magnabot flex 96 magnetic separation device

If you are located in the EEA, the United Kingdom, or Switzerland, you can change your settings at any time by clicking Manage Cookie Consent in the footer of our website.

Our website does not fully support your browser. We've detected that you are using an older version of Internet Explorer. Your commerce experience may be limited. Please update your browser to Internet Explorer 11 or above. Dismiss

The MagnaBot FLEX 96 Magnetic Separation Device is designed for high-throughput bioseparation using magnetic particles such as MagneSil Paramagnetic Particles. This method uses the principle of magnetic separation as an alternative to vacuum filtration and centrifugation separation formats. For best results, use a multiwell plate that is free of flashing or support in the interstitial space between every 4 wells, such as 2ml Nunc 96-Well Polypropylene DeepWell Storage Plates (Cat.# AS9307 or Thermo Fisher Cat.# 278743).

cookiescookiescookiescookiescookiescookies

Related News
  1. carpco gravity separator
  2. spiral chutes for chrome ore separation 13 min min for sale
  3. new potash feldspar spiral chute separator in leon
  4. almaty high end medium basalt spiral chute separator sell at a loss
  5. us patent 4 795 553 spiral separator patents com
  6. magnetic oil drain plug
  7. high quality hydro cyclone classifier separation machine for non ferrous minerals
  8. spiral chute separator adalah
  9. magnetic 0png
  10. what is the core meaning of magnetic separation
  11. sand vibrating grizzly screen
  12. powder making grinding mill uae
  13. turkis gold processing machine
  14. briquetting plant #740155
  15. stone crusher unit in dubai
  16. industrial mushroom dryer
  17. dryer rotary drum
  18. coal slime hammer crushers for stone crushing
  19. bridgeport puck ring mill grinding machine
  20. portable granite pellet machine in tabriz