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Ultras have traditionally been curated for athletes and have been anchored in competition and driven by an exclusive sports culture. LUNA reframes the Ultra athletics experience to inspire participants to engage in the sport for the first time AND to invite established athletes to join a more inclusive and culture driven ultra challenge.

The Americas Latino Eco Festival XIII (ALEF), a flagship program of AFC+A, has teamed up with Colorado's Human Potential Running Series to offer this unique Latino Ultra Nature Experience. Join us on Saturday, June 1, 2024 and kick off your ALEF experience with a unique adventure in the mountains of Golden, CO.

The experience features distances of 5km, 8-Mile, a Half Marathon (13.1 miles), and 50km (32 miles). On your journey you'll explore the incredibly gorgeous Golden Gate Canyon State Park. We'll explore the intersection between urban development and population growth with its lasting effects on the surrounding landscape and ecosystems and We'll share stunning views of Colorado's Continental Divide.

LUNA is a nonprofit event intent on bridging inclusion gaps in the outdoor recreation and sports workspace. For this reason we are requiring only a nominal sign up fee. Youth 16 and under pay no fees but must still register. All participants are encouraged to make a tax deductible DONATION to support the inclusive mandate of our program and the efforts of our staff and volunteers. Donate Additional Here: _button_id=DKNQHA5C428QW

Forest Bathing Research Spotlight

Medical empirical research on forest bathing (Shinrin-yoku): a systematic review

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Prescribed time in nature linked to improvements in anxiety, depression and blood pressure

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Ultra Nature Products are Approved by the TGA where required, and, if so, carry an Aust L number on front of the product packaging.

The only product in our range that is not TGA approved is the Ultra Nature Propolis and Manuka Honey Oral Spray. 

This product is classified as a food supplement due to the Manuka Honey Content, hence it does not require TGA Approval.

Ultra Nature products are available in many pharmacies and health food stores around Australia. For your convenience, you can also shop online right here at ultranature.com.au or view our stockists here.

We recommend referring to the label for safe storage guidance. In general, with any supplement, it is always recommend that you store them at an average room temperature of 25C and you must not store them in direct sunlight or near heat.

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To characterize the off-target activity of AsCas12a Ultra, we first performed GUIDE-seq experiments in HEK293 cells. Among 6 guides tested (Supplementary Table 9), we found a variable and low levels of signal for WT enzyme even at on-target sites. With similar sequencing depth, robust on-target signals were recovered for AsCas12a Ultra with limited off-target sites, suggesting this enzyme retained high on-target specificity at a genome-wide level (Supplementary Fig. 8). As off-target editing is a significant concern for the development of clinical cell therapies, we next examined the off-target profiles of AsCas12a Ultra in primary human T cells. Since guide activity is a limiting factor of the GUIDE-seq assay, we intentionally selected crRNAs with the highest on-target activity from our screens of the B2M, TRAC, and CIITA loci, in order to maximize the recovery of both on- and off-target signals for AsCas12a Ultra. Of note, these guides are intrinsically more potent than the others, where 90% editing efficiency was achieved even using WT enzyme (Fig. 3F). GUIDE-seq results indicated no detectable tag incorporation for any of the guides (Fig. 3G). As a positive control, we performed GUIDE-seq on WT-SpCas9 using a sgRNA targeting EMX1 (Fig. 3H). The same set of off-targets was recovered as previously published, therefore validating the performance of our GUIDE-seq procedure in primary T cells. Overall, AsCas12a Ultra has high specificity in primary cells, a particularly crucial property for cell therapy applications.

Recent reports called into question the utility of AsCas12a to mediate robust HDR, where it was observed that AsCas12a exhibits non-specific single-stranded DNA cleavage activity after binding31,33,44, raising concern that AsCas12a is not compatible with HDR-mediated targeted integration. Our results invalidate this concern and in fact, demonstrate robust knock-in is possible with AsCas12a using either ssODNs or AAV6 as donor templates. However, our data do not rule out that ssDNA cleavage activity may explain why higher RNP concentrations boost knockout efficiency, but not knock-in efficiency. Using AAV6, knock-in efficiency reached up to 60% in T cells, 50% in NK cells, and 30% in HSPCs. We observed nearly 40% double knock-in efficiency in T cells, which represents greater than a twofold improvement over a previous report using wild-type LbCas12a33. In NK cells, we observed knockout efficiencies above 90% and show that the TGFBR2 edit significantly enhances tumor killing in a model intended to mimic the tumor microenvironment of difficult-to-treat solid tumors. We also show knock-in efficiencies up to 50% using a single transgene. Furthermore, we demonstrate, for the first time, site-specific insertion of an anti-tumor antigen-directed CAR with AsCas12a Ultra significantly increases the anti-tumor activity of NK cells. These data demonstrate the clinical potential of the AsCas12a Ultra platform for making engineered NK cells for cancer immunotherapy.

Taken together, AsCas12a Ultra maximizes editing efficiency without compromising specificity, greatly expanding the gene-editing toolbox for researchers and clinicians regardless of cell type. These advances open the door for this nuclease to help patients reap the benefits of gene editing.

We would like to thank Nathan Roberts, Tina Luebke, Jeff Manthey, Joseph Dobosy, Thomas Swartjes, Stephen Winston, and members of the Editas Lead Discovery Group for their scientific contributions to this work.

C.A.V., J.A.Z., and M.A.B. conceived the project. L.Z. performed the bacterial selection, protein purification, in vitro biochemistry, and some experiments in human cell lines. R.T., B.T., S.E.G., N.M.B., S.F.B., and M.S.S. performed various experiments to characterize protein activity in human cell lines. H.T.R. analyzed the Spec-seq/SEAM-seq data. M.A.C. performed GUIDE-seq experiment in cell lines. R.V, J.N.E., S.L., S.N.S., K.M.W., S.S., C.M.B., and J.A.Z. performed experiments in primary human cells. G.L.K. and M.S.M. provided bioinformatics support. C.A.F., V.E.M., R.A.M., M.A.B. supervised the overall study. L.Z., C.A.V., and J.A.Z. wrote manuscript with input from all authors.

H.T.R. declares no competing financial interests. L.Z., R.T., B.T., S.E.G., M.A.C., N.M.B., S.F.B., M.S.S., G.L.K., M.S.M., M.A.B., and C.A.V. are employees of Integrated DNA technologies, (IDT), which sells reagents described in this manuscript. C.A.V. and M.A.B. own equity in the Danaher Corporation, which is the parent company of Integrated DNA Technologies. J.A.Z., R.V., S.L., S.N.S., K.M.W., and S.S. are current employees and shareholders of Editas Medicine. J.N.E., C.M.B., C.A.F., V.E.M., and R.A.M. are previous employees and shareholders of Editas Medicine and were employed by Editas at the time this work was conducted. Editas Medicine uses the reagents described in this manuscript to generate cell medicines. IDT and Editas Medicine have filed patents pertaining to the work described in this manuscript. Integrated DNA Technologies has a pending patent application (US20200109382A1) for the AsCas12a mutants described in this manuscript (C.A.V., L.Z., N.M.B., M.A.C., and M.A.B.). Editas Medicine has a patent pending (WO2019178426A1) for some of the clinical genome editing methods described in this manuscript (J.A.Z.). 152ee80cbc

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