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1
Tanaka, Kimiaki. "Wallpaintings and Mandalas at bSam-yas." JOURNAL OF INDIAN AND BUDDHIST STUDIES (INDOGAKU BUKKYOGAKU KENKYU) 35, no. 1 (1986): 472–69. http://dx.doi.org/10.4259/ibk.35.472.
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Chayet, Anne. "Le monastère de bSam-yas : sources architecturales." Arts asiatiques 43, no. 1 (1988): 19–29. http://dx.doi.org/10.3406/arasi.1988.1232.
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BUFFETRILLE, K. "La restauration du monastère de bSam yas." Journal Asiatique 277, no. 3 (1989): 363–411. http://dx.doi.org/10.2143/ja.277.3.2011505.
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Mémet, Sébastien. "Le monastère de bSam-yas : essai de restitution." Arts asiatiques 43, no. 1 (1988): 30–32. http://dx.doi.org/10.3406/arasi.1988.1233.
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MAKIDONO, Tomoko. "dGe rtse Mahapandita's Understanding of the bSam yas Debate." Journal of Indian and Buddhist Studies (Indogaku Bukkyogaku Kenkyu) 64, no. 1 (2015): 487–82. http://dx.doi.org/10.4259/ibk.64.1_487.
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Kellner, Birgit. "Where Did Kamalaśīla Compose His Works, and Does It Even Matter? Reflections on the Activities of Indian Scholars in Imperial Tibet." Asiatische Studien - Études Asiatiques 77, no. 1 (2023): 245–75. http://dx.doi.org/10.1515/asia-2023-0003.
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Abstract This article reflects on the activities of the Indian Buddhist scholar-monk Kamalaśīla (c. 740–795) in imperial Tibet. Following accounts offered by Tibetan historians of later periods, these activities have so far been understood as more or less limited to Kamalaśīla’s victorious participation in the historically momentous “Great Debate” at Bsam yas monastery against the Chinese Chan master Heshang Moheyan. This article suggests that he also composed altogether seven of his works – and possibly more – while residing in Tibet, and sketches aspects of his intellectual profile on this basis. While remaining focused on Kamalaśīla, the article also raises wider-ranging questions regarding the activities of Indian Buddhist scholars in imperial Tibet against the backdrop of interconnected histories across South, Central and East Asia.
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Cho, Joon Ho. "Sudden and Gradual Enlightenment of the Bsam yas Debate and Buddha-recollection of Master Cheonghwa." Korean Institute for Buddhist Studies 53 (August 31, 2020): 75–108. http://dx.doi.org/10.34275/kibs.2020.53.075.
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Laish, Eran. "The Embodiments of View: Simultaneous and Gradual Approaches in the Contemplative Typology of the Great Perfection." SMARATUNGGA: JURNAL OF EDUCATION AND BUDDHIST STUDIES 3, no. 2 (2023): 73–90. http://dx.doi.org/10.53417/sjebs.v3i2.111.
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The assertion of a state which is unconditioned and beyond temporal change creates unavoidable tensions for any Buddhist account that concerns the shift from worldly experience to a liberated one. The presence of such tensions can be found in the controversy between simultaneous (cig char; yugapad) and gradual (rim gyis; krameṇa) conceptions of the contemplative path and the state of liberation itself. This controversy found its early Tibetan expression in the so-called bSam yas debate, in which representative figures of both approaches argued about basic contemplative and soteriological issues. Later on, Klong chen pa, the renowned 14th century Tibetan teacher, explicated several contemplative typologies that included elements from both approaches. This research belongs to qualitative research using two interpretative perspectives, namely the Pragmatic attitude that focuses on the actual results of the scheme and the Transcendental point of view. The results showed that by examining the typologies and their presuppositions it becomes clear how the efficacy of each approach is closely related to individual capacities of practitioners. As such, the tension between simultaneous and gradual models is revealed as deeply contextual and not binary.
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Yan, Hong, Luyao Bao, Chenglong Liu, et al. "Abstract LB368: A first-in-class CTLA-4×TIGIT BsAb selectively targets tumor-associated Treg cells to improve the safety profile of CTLA-4 targeting therapy." Cancer Research 85, no. 8_Supplement_2 (2025): LB368. https://doi.org/10.1158/1538-7445.am2025-lb368.
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Abstract Background: Ipilimumab, an immune-checkpoint inhibitor, has demonstrated clinical benefits but is also associated with adverse events due to its effects on peripheral regulatory T cells (Tregs). Thus, selective targeting tumor-associated Tregs could improve the safety profile of ipilimumab. Based on this hypothesis, we developed a CTLA-4×TIGIT bispecific antibody (BsAb). By targeting CTLA-4 and TIGIT, it could selectively engage tumor-associated Tregs that co-express both markers, while minimizing its impact on peripheral Tregs, thereby reducing the toxicity associated with ipilimumab. Method: Bioinformatics was applied to analyze the expression profile of CTLA-4 and TIGIT on immune cells including Tregs derived from human peripheral blood mononuclear cells and tumor infiltrating lymphocytes. In vitro, we established CHO-K1-CTLA4 cells representing peripheral Tregs and CHO-K1-CTLA-4/TIGIT cells representing tumor-associated Tregs. CTLA-4/CD80 blockage and ADCC activity of CTLA-4×TIGIT BsAb were determined on these cells. Functionally, we evaluated T cell activation with CTLA-4×TIGIT BsAb treatment. ADCC activity of BsAb towards ex vivo expanded Tregs was also determined. In vivo, the MC38 syngeneic model in hCTLA-4/hTIGIT C57BL/6 mice was applied to validate the anti-tumor activity of the BsAb. The safety profile was evaluated in cynomolgus monkeys through a 4-week Good Laboratory Practice (GLP) toxicity study. Results: Single-cell sequencing analysis revealed the selective co-expression of CTLA-4 and TIGIT on tumor-associated Tregs compared to peripheral Tregs. CTLA-4×TIGIT BsAb was designed with one arm targeting CTLA-4 and another arm targeting TIGIT. Compared to the parental CTLA-4 antibody, the monovalent binding to CTLA-4 reduced the binding and blocking activity in CHO-K-1-CTLA4 cells. But due to its co-targeting to CTLA-4 and TIGIT, CTLA-4×TIGIT BsAb exerted good binding avidity and CTLA-4/CD80 blockage activity in CHO-K1-CTLA-4/TIGIT cells. Moreover, it exhibited potent ADCC activity towards CHO-K1-CTLA-4/TIGIT cells and ex vivo expanded Tregs. In the MC38 syngeneic model, CTLA-4×TIGIT BsAb exhibited potent anti-tumor activity and selective depletion of tumor-associated Tregs without affecting peripheral Tregs. In the GLP toxicity study, the CTLA-4×TIGIT BsAb exhibited a more favorable safety profile than CTLA-4 mAbs such as ipilimumab and tremelimumab. Conclusion: Our preclinical study thoroughly evaluated the in vitro and in vivo activity of the CTLA-4×TIGIT BsAb and demonstrated its mechanism of action in targeting tumor-associated Tregs, which confirms that the specificity towards tumor-associated Treg cells preserves efficient anti-tumor activity while enhancing the safety profile of CTLA-4 targeting therapy. The GLP toxicity study demonstrated that CTLA-4×TIGIT BsAb is expected to reduce peripheral adverse reactions and improve tolerance. The promising preclinical data support its advancing into clinical testing, and an Investigational New Drug (IND) application to NMPA has been submitted in Dec 2024. Citation Format: Hong Yan, Luyao Bao, Chenglong Liu, Simeng Chen, Wei Zhang, Xing Sun, Wenjing Cheng, Zeyun Xue, Wei Wang, Jimin Yuan, Cheng Liao. A first-in-class CTLA-4×TIGIT BsAb selectively targets tumor-associated Treg cells to improve the safety profile of CTLA-4 targeting therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB368.
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Zhang, Yu, Xiang Wang, and Xiuping Zhou. "Functions of Yes-association protein (YAP) in cancer progression and anticancer therapy resistance." Brain Science Advances 8, no. 1 (2022): 1–18. http://dx.doi.org/10.26599/bsa.2022.9050008.
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The Hippo pathway, a highly conserved kinase cascade, regulates cell proliferation, apoptosis, organ size, and tissue homeostasis. Dysregulation of this pathway reportedly plays an important role in the progression of various human cancers. Yes-association protein (YAP), the Hippo pathway’s core effector, is considered a marker for cancer therapy and patient prognosis. In addition, studies have indicated that YAP is involved in promoting anticancer drug resistance. This review summarizes current knowledge on YAP’s role in cancer progression, anticancer drug resistance, and advances in the development of YAP-targeting drugs. A thorough understanding of the complex interactions among molecular, cellular, and environmental factors concerning YAP function in cancer progression may provide new insight into the underlying mechanism of anticancer drug resistance. It might lead to improved prognosis through novel combined therapies.
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Yao, Sufei, Chengzhang Shang, Zhuolin Li, et al. "Abstract 2618: BCG017, a bispecific ADC targeting PTK7 and EGFR exhibits anti-tumor efficacy in PDX models." Cancer Research 84, no. 6_Supplement (2024): 2618. http://dx.doi.org/10.1158/1538-7445.am2024-2618.
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Abstract EGFR is a favored target in various cancer therapies. However, EGFR-based treatments have been challenged by drug resistance and cytotoxicity. Targeting EGFR with an antibody-drug conjugate (ADC) is a promising new therapeutic strategy to address the drug resistance, due to the potent killing effects of the payload. Furthermore, we hypothesized that development of a bispecific ADC (bsADC) targeting EGFR and another tumor-associated antigen (TAA) might improve the tumor selectivity, thereby limiting the on-target off-tumor toxicity. One such TAA candidate is PTK7, which belongs to the same receptor tyrosine kinase family as EGFR, and is co-expressed with EGFR in multiple types of solid tumors, including lung, esophageal, head and neck, and colon cancers. Herein, we developed a fully human anti-human PTK7 EGFR bsAb using our proprietary common light chain RenLite® mouse platform and knobs-into-holes technology. The anti-PTK7 EGFR bsAb demonstrates good purity by SEC-HPLC, and can cross-react with human and cynomolgus monkey antigens with favorable affinity. The PTK7 x EGFR bsAb demonstrated higher binding to various types of cancer cell lines, as well as enhanced internalization in vitro compared with PTK7 parental antibody. Next, the bsAb was conjugated with monomethyl auristatin E (MMAE) to generate an anti-PTK7 x EGFR bsADC, BCG017, with a drug-to-antibody ratio of approximately 4. BCG017 demonstrated superior anti-tumor activity compared to benchmarks and its PTK7 parental ADC in cell-derived non-small-cell lung cancer (NSCLC) xenografts, and showed enhanced anti-tumoractivity when compared to benchmark ADCs and parental ADCs in patient-derived breast and pancreatic ductal adenocarcinoma xenograft models. These results suggest that BCG017 have the potential to be a novel therapeutic alternative for PTK7 and EGFR co-expressing tumors. Citation Format: Sufei Yao, Chengzhang Shang, Zhuolin Li, Gao An, Chaoshe Guo, W. Frank An, Yi Yang. BCG017, a bispecific ADC targeting PTK7 and EGFR exhibits anti-tumor efficacy in PDX models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2618.
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Yang, Yongfei, Xiaoxia Sun, Ziyan Li, et al. "Abstract 2724: BCG020, a novel bispecific antibody targeting EGFR and CD70, is effective against EGFR and CD70 high expressed tumors." Cancer Research 84, no. 6_Supplement (2024): 2724. http://dx.doi.org/10.1158/1538-7445.am2024-2724.
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Abstract The epidermal growth factor receptor (EGFR) is highly expressed across a wide range of different cancers, and is a known driver of cancer growth; EGFR upregulation is frequently associated with adverse prognosis. Many patients undergoing EGFR-TKI (tyrosine kinase inhibitors) treatment will acquire resistance, which can be accompanied by increased expression of CD70 in some cancers. Simultaneous engagement of both EGFR and CD70 with a bispecific antibody (bsAb) is a potential strategy to overcome such resistance and achieve greater efficacy. To explore this strategy, we developed a novel IgG1 bsAb, BCG020, targeting EGFR and CD70. The parental EGFR antibody and CD70 antibody were developed from fully human common light chain antibody mice (RenLite®). When compared to EGFR benchmarks, the parental EGFR antibody exhibits similar affinity to both human and cynomolgus monkey EGFR, similar internalization activity in EGFR+ tumor cell lines, and superior blocking activity of EGF to EGFR in vitro. Furthermore, the EGFR parental antibody demonstrates good stability. The parental CD70 antibody exhibits high affinity to both human and monkey CD70, with superior internalization activity to benchmark antibody in CD70+ tumor cell lines, as well as superior blockade of CD70-induced signaling of CD27-Luc when compared to benchmark antibodies. When assembled into a bsAb, BCG020 exhitibs the same high affinity as both parental antibodies, with higher internalization activity than parental antibodies and benchmark antibodies. To evaluate the efficacy of BCG020 in vivo, we established cell line-derived xenograft (CDX) models in immunodeficient (B-NDG) mice. We observed that BCG020 treatment (10 mg/kg) potently inhibited growth of EGFR+CD70+ tumors. Taken together, these data indicate that BCG020 is a first-in-class bispecific antibody with potential to treat solid tumors with high expression of EGFR and CD70. Citation Format: Yongfei Yang, Xiaoxia Sun, Ziyan Li, Yue Yan, Linpeng Xu, Xiaoxue Wu, Luheng Du, Ying Zhu, Chaoshe Guo, W. Frank An. BCG020, a novel bispecific antibody targeting EGFR and CD70, is effective against EGFR and CD70 high expressed tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2724.
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Corianò, Claudio, and Antonio Costantini. "Extra Quarks and Bileptons in BSM Physics in a 331 Model." EPJ Web of Conferences 192 (2018): 00034. http://dx.doi.org/10.1051/epjconf/201819200034.
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We describe some salient features of the 331F (Frampton-Pisano-Pleitez) bilepton model, in which the constraints of anomaly cancelation require the number of generations to be three. In a class of six models, four of which characterised by a β parameter describing the embedding of the hypercharge in the SU(3)L symmetry, a specific choice for β allows bileptons in the spectrum, i.e. vectors and scalars of lepton numbers ±2. At the same time the model allows exotic quarks, with the third quark generation treated asymmetrically respect to the other two. Bileptons generate specific signatures in the form of multilepton final states in Drell-Yan like processes, with and without associated jets, which can be searched for at the LHC.
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Yao, Sufei, Chengzhang Shang, Gao An, Chaoshe Guo, W. Frk an, and Yi Yang. "Abstract 2616: BCG033, a novel bispecific antibody-drug conjugate targeting PTK7 and TROP2, demonstrates preclinical efficacy against triple-negative breast cancer and other solid tumor xenografts." Cancer Research 84, no. 6_Supplement (2024): 2616. http://dx.doi.org/10.1158/1538-7445.am2024-2616.
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Abstract Metastatic triple-negative breast cancer (TNBC) patients have poor overall survival, highlighting the need for novel treatments. Although the TROP2-targeting ADC sacituzumab govitecan recently received accelerated approval from the FDA for the treatment of patients with metastatic TNBC, the on-target toxicity of this single-target agent has limited clinical efficacy. We sought to improve the specificity and efficacy of future TNBC-targeted therapies by generating a bispecific antibody-drug conjugate (bsADC) targeting TROP2 and PTK7, another tumor-associated antigen (TAA) that is highly expressed in TNBC and correlates with poor prognosis and metastatic disease. We previously generated fully human antibodies targeting PTK7 and TROP2 from Biocytogen’s fully human, common light chain antibody transgenic RenLite® mice, which were selected such that their monovalent antibodies exhibited reduced internalization profiles for improved tumor selectivity. These antibodies were then constructed into a bispecific antibody targeting PTK7 × TROP2, which demonstrated reactivity to human and cynomolgus monkey antigens and binding to multiple cancer cell lines, including TNBC, with high affinity. PTK7 × TROP2 bsAb also showed enhanced internalization in vitro compared with parental monovalent antibodies. Next, the PTK7 x TROP2 bsAb was conjugated to vcMMAE with a drug-to-antibody ratio (DAR) of 4 to generate a bsADC (BCG033). BCG033-vcMMAE demonstrated superior activity to benchmark and parental ADCs in a cell line-derived xenograft (CDX) TNBC model with low PTK7 expression. Here, we demonstrate that BCG033-vcMMAE ADCs also exhibited superior efficacy to benchmark ADCs in PDX models, including TNBC xenografts and NSCLC xenografts. We next tested the efficacy of the PTK7 x TROP2 bsAb conjugated to BLD1102, Biocytogen’s novel, proprietary linker/payload composed of a DNA Topo I inhibitor payload and a highly hydrophilic protease-cleavable linker, with a DAR of 8. BCG033-BLD1102 showed potent activity in a colorectal cancer PDX model in which benchmark ADCs were inactive, even at high doses. In summary, BCG033 conjugates demonstrate promising preclinical efficacy in vivo, which ultimately could provide a new treatment option for TNBC and other solid tumors expressing PTK7 and TROP2. Citation Format: Sufei Yao, Chengzhang Shang, Gao An, Chaoshe Guo, W. Frk an, Yi Yang. BCG033, a novel bispecific antibody-drug conjugate targeting PTK7 and TROP2, demonstrates preclinical efficacy against triple-negative breast cancer and other solid tumor xenografts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2616.
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Lange, Diana. ""A Unique View from within": The Representation of Tibetan Architecture in the British Library's Wise Collection." December 3, 2016. https://doi.org/10.5281/zenodo.3560679.
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Justin, Kelley. "Nyingma (rnying ma)." Database of Religious History, June 27, 2024. https://doi.org/10.5281/zenodo.12574301.
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The Nyingma, or "Ancient" lineage refers to the oldest of the four major lineages of Tibetan Buddhism. Distinguished from followers of the later Sarma (Tibetan: gsar ma) lineages, which includes the Kadam, Sakya, Kagyu, and later Gelug, Nyingma refers to those who adhere to the earliest (pre-tenth century) translations of Buddhist teachings arriving in Tibet, as well as a series of treasure (T: gter ma) text revealed from the eleventh century onwards. Renowned for their adherence to a range of esoteric, predominantly tantric Buddhist practices, as well as unorthodox behavior, Nyingma followers served as motivation for periodic reforms throughout Tibetan history, each allegedly "returning" to the ethical roots and meditative discipline of Indian Buddhism. According to the Nyingma lineage, the primordial teacher is Samantabhadra (T: kun tu bzang po). Depicted without clothing and vivid blue in color, he represents the untainted wisdom of the all Buddhas of the three times and ten directions. In human form, the Nyingma lineage finds its roots in the Indian master Padmasambhava (T: pad+ma 'byung gnas) who is credited with introducing the first coherent and comprehensive presentation of the Buddhist path to Tibet. He is often referenced along with Shantarakshita (Sansrkit: Śāntarakṣita), the great Indian pandit, and Vairotsana (T: bai ro tsa na), the great translator, delineating the three most important early Nyingma thinkers. The historical center of the lineage is found in Samye (T: bsam yas) monastery in central Tibet. Constructed in the eighth century, Samye monastery was the first successfully constructed monastery in Tibet. After years of wrestling with demons, King Trisong Detsen (T: khri srong lde btsan), requested Padmasambhava to subjugate the antagonistic demon, which he did, and the monastery was miraculously completed overnight. Renowned today for their erudite descriptions of the Great Completeness (T: rdzogs pa chen po) meditative system, the Nyingma lineage experienced a resurgence in the fourteenth century with the renowned scholar-yogi Longchen Rabjam (T: klong chen rab 'byams). Longchenpa, as he is commonly referred to, both revealed new treasure teachings and consolidated much of the existent tantric materials found within the early Nyingma lineage. His extensive writings on topics such as the nine vehicles (T: theg pa dgu; a defining religious shema of the Nyingma, the subtle body, meditation practice, and most importantly the Great Completeness, revived the Nyingma lineage during and after his life. Extending across the Tibetan plateau to include all three Tibetan states (Utsang, Kham, and Amdo), as well as Bhutan and modern-day Indian state of Ladakh, the Nyingma lineage flourished in many sub-lineages throughout the centuries, resulting in a vibrant array of contemplative and scholarly practices.
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van Roode, Mark, and Arun K. Bhattacharya. "Durability of Oxide/Oxide Ceramic Matrix Composites in Gas Turbine Combustors." Journal of Engineering for Gas Turbines and Power 135, no. 5 (2013). http://dx.doi.org/10.1115/1.4007978.
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An integrated creep rupture strength degradation and water vapor degradation model for gas turbine oxide-based ceramic matrix composite (CMC) combustor liners was expanded with heat transfer computations to establish the maximum turbine rotor inlet temperature (TRIT) for gas turbines with 10:1 pressure ratio. Recession rates and average CMC operating temperatures were calculated for an existing baseline N720/A (N720/Al2O3) CMC combustor liner system with and without protective Al2O3 friable graded insulation (FGI) for 30,000-h liner service life. The potential for increasing TRIT by Y3Al5O12 (YAG) substitution for the fiber, matrix, and FGI constituents of the CMC system was explored, because of the known superior creep and water vapor degradation resistance of YAG compared to Al2O3. It was predicted that uncoated N720/A can be used as a combustor liner material up to a TRIT of ∼1200 °C, offering no TRIT advantage over a conventional metal + thermal barrier coating (TBC) combustor liner. A similar conclusion was previously reached for a SiC/SiC CMC liner with barium strontium aluminum silicate (BSAS)-type environmental barrier coating (EBC). The existing N720/A + Al2O3 FGI combustor liner system can be used at a maximum TRIT of ∼1350 °C, a TRIT increase over metal + TBC, and uncoated N720/A of ∼150 °C. Replacing the Al2O3 with YAG is predicted to increase the maximum allowable TRIT. Substitution of the fiber or matrix in N720/A increases TRIT by ∼100 °C. A YAG FGI improves the TRIT of the N720/A + Al2O3 FGI by ∼50 °C, enabling a TRIT of ∼1400 °C, similar to that predicted for SiC/SiC CMCs with protective rare earth monosilicate EBCs.
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Cian, Duggan, Tumtas Yasin, and O. Bozkurt Tolga. "A golden-gate compatible TRV2 virus induced gene silencing (VIGS) vector." November 10, 2021. https://doi.org/10.5281/zenodo.5667431.
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Virus induced gene silencing (VIGS) is a useful tool in plant biology to systemically silence a gene by RNA interference (RNAi). Co-expression of tobacco rattle virus 1 (TRV1), which contains the genome of the viral vector, with TRV2 containing the target sequence for RNAi, can be achieved by Agrobacterium-mediated gene expression in Nicotiana benthamiana (Burch-Smith et al., 2006). Existing methods of cloning TRV2 plasmids with the targeting sequence of interest include time consuming Restriction-Ligation cloning, expensive Gateway cloning or Ligation Independent Cloning (LIC). Whilst LIC is relatively quick and cost-effective, it relies on having a pre-linearised vector. Therefore, Golden-Gate cloning is preferable in that it is a 1-step cloning method. Therefore, we modified the existing TRV2 vector to be compatible with golden gate cloning. To add extra flexibility, we incorporated the overhangs used for pRNAiGG, a vector for carrying out transient, local silencing in leaf tissue by hairpin RNAi (Yan et al., 2012). Therefore, the resulting TRV2gg is compatible with the same insert for pRNAiGG enabling transient, local silencing or systemic silencing. TRV2gg contains an unwanted BsaI recognition site in the backbone, however a simple golden gate protocol of 37˚C for 2 h or a protocol that ends with a ligation-optimised step, is sufficient to easily clone multiple positive colonies.