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In order to capture in a quantitative way the nuance necessary to distinguish man from woman, it is necessary for a model to associate more than a single number to the word pair. A natural and simple candidate for an enlarged set of discriminative numbers is the vector difference between the two word vectors. GloVe is designed in order that such vector differences capture as much as possible the meaning specified by the juxtaposition of two words.
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As one might expect, ice co-occurs more frequently with solid than it does with gas, whereas steam co-occurs more frequently with gas than it does with solid. Both words co-occur with their shared property water frequently, and both co-occur with the unrelated word fashion infrequently. Only in the ratio of probabilities does noise from non-discriminative words like water and fashioncancel out, so that large values (much greater than 1) correlate well with properties specific to ice, and small values (much less than 1) correlate well with properties specific of steam. In this way, the ratio of probabilities encodes some crude form of meaning associated with the abstract concept of thermodynamic phase.
The training objective of GloVe is to learn word vectors such that their dot product equals the logarithm of the words' probability of co-occurrence. Owing to the fact that the logarithm of a ratio equals the difference of logarithms, this objective associates (the logarithm of) ratios of co-occurrence probabilities with vector differences in the word vector space. Because these ratios can encode some form of meaning, this information gets encoded as vector differences as well. For this reason, the resulting word vectors perform very well on word analogy tasks, such as those examined in the word2vec package.
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Convert word vectors for usewith spaCy. Will export an nlp object that you can use in the[initialize] block of your config toinitialize a model with vectors. See the usage guide onstatic vectors for details onhow to use vectors in your model.
Fares, Murhaf; Kutuzov, Andrei; Oepen, Stephan & Velldal, Erik (2017). Word vectors, reuse, and replicability: Towards a community repository of large-text resources, In Jrg Tiedemann (ed.), Proceedings of the 21st Nordic Conference on Computational Linguistics, NoDaLiDa, 22-24 May 2017. Linkping University Electronic Press. ISBN 978-91-7685-601-7
If you compare results from other tools, you will notice that Vector Magic produces vectors that are more faithful to the bitmap original. This makes them often immediately usable, and if cleanup is required there's much less of it.
We describe receptor-targeted adeno-associated viral (AAV) vectors that allow genetic modification of rare cell types ex vivo and in vivo while showing no detectable off-targeting. Displaying designed ankyrin repeat proteins (DARPins) on the viral capsid and carefully depleting DARPin-deficient particles, AAV vectors were made specific for Her2/neu, EpCAM or CD4. A single intravenous administration of vector targeted to the tumour antigen Her2/neu was sufficient to track 75% of all tumour sites and to extend survival longer than the cytostatic antibody Herceptin. CD4-targeted AAVs hit human CD4-positive cells present in spleen of a humanized mouse model, while CD8-positive cells as well as liver or other off-target organs remained unmodified. Mimicking conditions of circulating tumour cells, EpCAM-AAV detected single tumour cells in human blood opening the avenue for tumour stem cell tracking. Thus, the approach developed here delivers genes to target cell types of choice with antibody-like specificity.
Given the high prevalence for anti-AAV antibodies in the human population, a general concern with systemic administrations of AAV vectors refers to neutralizing antibodies that may substantially reduce gene delivery5. We therefore performed transduction experiments with Her2-AAV and CD4-AAV in the presence of pooled human serum (IVIG). Interestingly, we observed for both receptor-targeted AAVs an enhanced resistance towards neutralizing antibodies as compared with the parental AAV-2 (Fig. 3d).
Key to achieve receptor-specific gene delivery without detectable off-target transduction was the separation of DARPin-displaying particles from DARPin-deficient ones, which was possible by simple IMAC, exploiting the His-tag fused to the DARPin. AAV particles have been previously modified with His-tags to facilitate particle purification by HisTrap columns28,29. Moreover, position 587 of the AAV-2 capsid, previously identified as possible insertion site for His-tags29, has recently been exploited to separate DARPin-displaying and DARPin-deficient particles30. However, since His-tag and DARPin are not physically linked in this setting, recombination, which is a frequent event in packaging cells31, can give rise to DARPin-deficient but His-tag-displaying particles. Moreover, position 587 is embedded in the natural HSPG receptor binding motif32,33. The presence of positively charged residues as those of the His-tag at this position can reconstitute HSPG binding and natural receptor usage for cell entry34,35. Owing to these potential risks and the absence of a functional proof that a His-tag in position 587 indeed efficiently depletes DARPin-deficient particles30, we decided to place the His-tag N-terminally of the DARPin, thus avoiding both of the above mentioned risks. This step enhanced in addition gene delivery more than 10-fold. While the enhanced gene delivery to target cells can be expected from greatly enriching DARPin-displaying AAV particles (Fig. 1b, left and right chromatogram), the reduced off-target transduction suggests that the presence of the DARPins interferes with the uptake of receptor-blinded vectors into non-target tissue. As an example, CD4-AAV, the as of yet first non-enveloped viral vector that efficiently transduces lymphocytes, modified CD4-positive human cells in the applied mouse model but did not detectably transduce any mouse or CD4-negative human cells. Moreover, Her2-AAV detected the majority of metastases present in a tumour mouse model after only a single systemic injection.
A general concern with systemic administrations of AAV vectors to patients refers to neutralizing antibodies that may substantially reduce gene delivery5. Interestingly, we observed an enhanced resistance towards neutralizing antibodies for receptor-targeted AAVs, suggesting that these vectors will be less sensitive towards inactivation by antibodies when administered to patients. Most likely, this is due to the mutations R585A and R588A, which were introduced to abolish natural receptor binding and are located near the highly immunogenic three-fold symmetry axis36. If required, this immune escape phenotype can be further improved by introducing additional mutations shown to interfere with binding of neutralizing antibodies37. Also, when administered to nave patients, receptor-targeting may likely reduce the level of induced immune responses. Reasons are the potential reduction in vector dose required, and the restricted expression and thus presentation of transgene products in target cells.
For the generation of plasmids encoding the DARPin-VP2 fusion constructs, the reading frames of the Her2-specific DARPin-9.29 (ref. 13), the CD4-specifc DARPin 55_2 (ref. 16) and the EpCAM-specific DARPin Ec1 (ref. 20) were amplified by PCR using the primer pair DARPin-for/DARPin-rev or DARPin-for/DARPin EC1-rev respectively, (Supplementary Table 1) and were inserted into pGFP (green fluorescent protein)-VP2 (ref. 21) by sticky-end ligation using AgeI and BsrGI restriction sites resulting in plasmids pHer2-VP2, pCD4-VP2 and pEpCAM-VP2. Plasmids encoding VP2 fused to His-tagged or Myc-tagged DARPins were generated analogously using the primer pairs His-forw/DARPin-rev or His-forw/DARPin EC1-rev and Myc-forw/DARPin-rev or Myc-forw/DARPin Ec1-rev, respectively. All AAV vectors were of self-complementary conformation and encoded gfp (pscGFP; 2,200 base pairs including ITRs), GL4-luciferase (pscLUC; 3,100 base pairs including ITRs) or HSV-TK (pscHSV-TK; 2,600 base pairs including ITRs)11 under control of the strong and ubiquitously active spleen focus-forming virus promoter41.
A3.01 (ATCC CRL-2570), A2.01 (ATCC CCL-120.1), Raji (ATCC CCL-86) and Jurkat (ATCC TIB-152) cells were grown in RPMI medium supplemented with 10% FCS and 1% glutamine. For the generation of CHO-EpCAM cells, the cDNA sequence of human EpCAM (pCMV6-AC-EpCAMcDNA, Origene, Rockville, USA) and a puromycin resistance gene were cloned into a lentiviral transfer vector resulting in the bicistronic plasmid pS-hEpCAM-IRES-puro-W. CHO-K1 cells were transduced with lentiviral vector particles having packaged the hEpCAM-IRES-puro sequence and were selected using puromycin for 2 weeks. The resulting CHO-EpCAM bulk cell population was stained for EpCAM expression and a single clone named CHO-EpCAM H1 was selected for further experiments. For the generation of MDA-MB-453-luc cells, MDA-MB-453 cells were transduced with lentiviral vectors transferring the luciferase gene44 at a multiplicity of infection of 0.5. A single-cell clone was analysed for luciferase and Her2/neu expression and was used for in vivo experiments. 0852c4b9a8
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