Journal articles: 'BRG'

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Kiefer, Márta, and Adam Török. "BRG." Eastern European Economics 36, no. 1 (January 1998): 9–18. http://dx.doi.org/10.1080/00128775.1998.11648647.

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Pini, Núbia Inocencya Pavesi, Luciana Manzotti De-Marchi, Bruno Frazão Gribel, Adilson Luiz Ramos, Laurindo Zanco Furquim, and Renata Corrêa Pascotto. "Analysis of width/height ratio and gingival zenith in patients with bilateral agenesis of maxillary lateral incisor." Dental Press Journal of Orthodontics 17, no. 5 (October 2012): 87–93. http://dx.doi.org/10.1590/s2176-94512012000500013.

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OBJECTIVE: The purpose of this study was to evaluate the width/length ratio and the gingival zenith (GZ), by means of dental casts and digital caliper, in patients with missing maxillary lateral incisors after treatment. METHODS: The sample was composed of 52 subjects divided into 3 groups: BRG (n = 18), patients with bilateral agenesis treated with tooth re-contouring; BIG (n = 10) patients with agenesis treated with implants and CG (n = 24), control group. The data were analyzed using Shapiro-Wilk, Spearman correlation, Wilcoxon, Kruskal-Wallis, t test and ANOVA tests (p < 0.05). RESULTS: For the width/length ratio of the lateral incisors, BIG presented the lowest mean values (0.72 right and left), when compared with other groups. However, comparison between groups presented statistically significant differences for the right lateral incisor (BIG x CG) and for the canine (BRG x CG). GZ data evaluation showed the greatest difference for BRG (0.5 right and 0.48 left). BIG (0.95 right and 0.98 left) and CG (0.98 right and 0.8 left) presented more similar values, nevertheless, without statistical difference (p > 0.05). GZ data for the right and left sides of the smile were not considered statistically different. CONCLUSION: Although no statistical difference was found in the comparison between the groups, analysis of the descriptive values showed that group BIG showed the greatest difference in values with regard to width/length ratio. Regarding gingival zenith, BRG showed the greatest difference.

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Jani, Anant, Mimi Wan, Jianmin Zhang, Kairong Cui, Jie Wu, Paula Preston-Hurlburt, Rohini Khatri, Keji Zhao, and Tian Chi. "A novel genetic strategy reveals unexpected roles of the Swi–Snf–like chromatin-remodeling BAF complex in thymocyte development." Journal of Experimental Medicine 205, no. 12 (October 27, 2008): 2813–25. http://dx.doi.org/10.1084/jem.20080938.

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We have developed a general strategy for creating littermates bearing either a tissue-specific point mutation or deletion in any target gene, and used the method to dissect the roles of Brg, the ATPase subunit of the chromatin-remodeling Brg-associated factor (BAF) complex, in early thymocyte development. We found that a point mutation that inactivates the Brg ATPase recapitulates multiple defects previously described for Brg deletion (Chi, T.H., M. Wan, P.P. Lee, K. Akashi, D. Metzger, P. Chambon, C.B. Wilson, and G.R. Crabtree. 2003. Immunity. 19:169–182). However, the point mutant helps reveal unexpected roles of Brg in CD25 repression and CD4 activation. Surprisingly, CD4 activation occurs independently of the Brg ATPase and is perhaps mediated by physical interactions between Brg and the CD4 locus. Our study thus suggests that the BAF complex harbors novel activities that can be necessary and even sufficient for stimulating transcription from an endogenous chromatin template in the absence of Brg-dependent remodeling of that template. We conclude that conditional point mutants, rarely used in mammalian genetics, can help uncover important gene functions undetectable or overlooked in deletion mutants.

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Ma, Zhendong, Mi Jung Chang, Reesha Shah, Jill Adamski, Xueyan Zhao, and Etty N. Benveniste. "Brg-1 Is Required for Maximal Transcription of the Human Matrix Metalloproteinase-2 Gene." Journal of Biological Chemistry 279, no. 44 (August 17, 2004): 46326–34. http://dx.doi.org/10.1074/jbc.m405438200.

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Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases whose aberrant expression are correlated with tumor invasion and angiogenesis. The transcription factors Sp1, Sp3, and AP-2 are required for constitutive expression ofMMP-2in tumor cells; however, the regulatory mechanisms ofMMP-2expression are not well understood. We investigated the involvement of Brg-1, the ATPase subunit of the SWI/SNF complex, in human MMP-2 gene transcription. Reconstitution of Brg-1 enhancesMMP-2transcription in Brg-1-deficient SW-13 cells. Chromatin immunoprecipitation assay demonstrates that Brg-1 is required for recruitment of Sp1, AP-2, and polymerase II to the MMP-2 promoter, whereas the binding of Sp3 to the MMP-2 promoter is decreased upon Brg-1 reconstitution. Furthermore, Sp1 interacts with Brg-1in vivo. Restriction enzyme accessibility assays indicate that accessibility of the MMP-2 promoter region is not changed in the absence or presence of Brg-1. These results illustrate the connection between the SWI/SNF complex and optimal expression ofMMP-2and highlight the critical function of Brg-1 in regulating the recruitment of Sp1, Sp3, AP-2, and polymerase II to the MMP-2 promoter.

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DiRenzo, James, Yongfeng Shang, Michael Phelan, Säid Sif, Molly Myers, Robert Kingston, and Myles Brown. "BRG-1 Is Recruited to Estrogen-Responsive Promoters and Cooperates with Factors Involved in Histone Acetylation." Molecular and Cellular Biology 20, no. 20 (October 15, 2000): 7541–49. http://dx.doi.org/10.1128/mcb.20.20.7541-7549.2000.

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ABSTRACT Several factors that mediate activation by nuclear receptors also modify the chemical and structural composition of chromatin. Prominent in this diverse group is the steroid receptor coactivator 1 (SRC-1) family, which interact with agonist-bound nuclear receptors, thereby coupling them to multifunctional transcriptional coregulators such as CREB-binding protein (CBP), p300, and PCAF, all of which have potent histone acetyltransferase activity. Additionally factors including the Brahma-related gene 1 (BRG-1) that are involved in the structural remodeling of chromatin also mediate hormone-dependent transcriptional activation by nuclear receptors. Here, we provide evidence that these two distinct mechanisms of coactivation may operate in a collaborative manner. We demonstrate that transcriptional activation by the estrogen receptor (ER) requires functional BRG-1 and that the coactivation of estrogen signaling by either SRC-1 or CBP is BRG-1 dependent. We find that in response to estrogen, ER recruits BRG-1, thereby targeting BRG-1 to the promoters of estrogen-responsive genes in a manner that occurs simultaneous to histone acetylation. Finally, we demonstrate that BRG-1-mediated coactivation of ER signaling is regulated by the state of histone acetylation within a cell. Inhibition of histone deacetylation by trichostatin A dramatically increases BRG-1-mediated coactivation of ER signaling, and this increase is reversed by overexpression of histone deacetylase 1. These studies support a critical role for BRG-1 in ER action in which estrogen stimulates an ER–BRG-1 association coupling BRG-1 to regions of chromatin at the sites of estrogen-responsive promoters and promotes the activity of other recruited factors that alter the acetylation state of chromatin.

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Mudhasani, Rajini, and Joseph D. Fontes. "The Class II Transactivator Requires brahma-Related Gene 1 To Activate Transcription of Major Histocompatibility Complex Class II Genes." Molecular and Cellular Biology 22, no. 14 (July 15, 2002): 5019–26. http://dx.doi.org/10.1128/mcb.22.14.5019-5026.2002.

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ABSTRACT The class II transactivator (CIITA) is the key regulator of major histocompatibility complex (MHC) class II gene transcription. We demonstrate here that CIITA requires the ATPase subunit of an hSWI/SNF complex, brahma-related gene 1 (BRG-1), to activate transcription. When introduced into a cell line lacking BRG-1, CIITA was unable to activate cellular MHC class II genes. Reexpression of the wild-type but not an ATP-binding-deficient BRG-1 protein in this cell line restored the ability of CIITA to transactivate transcription of MHC class II genes. Interestingly, when the activity of CIITA was assayed in the BRG-1-deficient cell line by using a plasmid-based reporter assay, BRG-1 was not required for transcriptional activation, suggesting that the chromatin structure on the plasmid is such that BRG-1 is not necessary. Coimmunoprecipitation experiments were performed to determine if BRG-1 and CIITA proteins associate with each other in cells. We found that the two proteins coimmunoprecipitate and that amino acids 1 to 140 of CIITA are sufficient for binding. Taken together, these data suggest that BRG-1 and, very likely, an hSWI/SNF complex are required for transcription of MHC class II genes. The complex is likely recruited to MHC class II promoters, at least in part, by interaction with CIITA.

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Camidge, D. Ross, Hye Ryun Kim, Myung-Ju Ahn, James Chih-Hsin Yang, Ji-Youn Han, Maximilian Hochmair, Ki Hyeong Lee, et al. "Association of depth of target lesion response to brigatinib with outcomes in patients with ALK inhibitor-naive ALK+ NSCLC in ALTA-1L." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): 9072. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.9072.

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9072 Background: In patients (pts) with crizotinib (CRZ)-refractory advanced ALK+ NSCLC in the phase 2 ALTA trial (NCT02094573), the depth of target lesion response to brigatinib (BRG) correlated with PFS and OS. Here, we examine the association of maximum decrease in target lesions with PFS and OS in ALTA-1L (NCT02737501), a randomized phase 3 trial of BRG vs CRZ in pts with ALK inhibitor-naive advanced ALK+ NSCLC. Methods: Pts were randomized 1:1 to receive BRG 180 mg qd (7-day lead-in at 90 mg; n=137) or CRZ 250 mg bid (n=138). Pts with target lesion assessment by blinded independent review committee (BIRC) were grouped based on greatest decrease from baseline per RECIST v1.1: none–50%, 51%–75%, and 76%–100% shrinkage. Outcomes in the ≤50% target lesion shrinkage group served as the comparator for outcomes in the 51%–75% and 76%–100% groups. Results: At study end (last pt contact: Jan 29, 2021), 124/137 pts in the BRG arm and 125/138 pts in the CRZ arm had ≥1 evaluable target lesion assessment; female (BRG/CRZ), 51%/59%; median age, 57.5/60.0 years. Median follow-up was 40.8/15.7 months. In BRG/CRZ arms, 76%-100% shrinkage was observed in 56%/34% of pts, 51%-75% shrinkage in 27%/30%, and ≤50% shrinkage in 16%/35%, respectively. BRG was associated with significantly more pts with target lesion shrinkage >75% vs CRZ ( P=0.0005), and a Cochran-Armitage trend analysis demonstrated significantly deeper response across all shrinkage groups for BRG compared with CRZ ( P<0.0001). A majority of pts in the BRG arm experienced 76%–100% target lesion shrinkage in all subgroups analyzed. Pts treated with BRG or CRZ with target lesion shrinkage >50% had lower risk of a PFS event (BRG HR [95% CI]: 51%–75% shrinkage, 0.58 [0.29–1.18]; 76%–100%, 0.23 [0.12–0.46]; CRZ: 51%–75% shrinkage, 0.68 [0.41–1.12]; 76%–100%, 0.26 [0.15–0.45]) or an OS event (BRG: 51%–75% shrinkage, 0.39 [0.17–0.89]; 76%–100%, 0.15 [0.07–0.35]; CRZ: 51%–75% shrinkage, 0.43 [0.21–0.85]; 76%–100%, 0.23 [0.10–0.50]) than pts with ≤50% shrinkage. Longer median time to PFS and OS and higher 4-year estimated OS rates were associated with depth of response in both arms (Table). Conclusions: In this exploratory post hoc analysis, BRG demonstrated significantly deeper target lesion response vs CRZ. Pts with >75% shrinkage had significantly reduced risk of a PFS or OS event vs pts with ≤50% target lesion shrinkage. Clinical trial information: NCT02737501. [Table: see text]

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Roncella, S., G. Cutrona, A. Favre, M. Ulivi, F. Fais, A. Signorini, CE Grossi, N. Chiorazzi, and M. Ferrarini. "Apoptosis of Burkitt's lymphoma cells induced by specific interaction of surface IgM with a self-antigen: implications for lymphomagenesis in acquired immunodeficiency syndrome." Blood 88, no. 2 (July 15, 1996): 599–608. http://dx.doi.org/10.1182/blood.v88.2.599.bloodjournal882599.

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In a previous study, we described a cell line (BRG-P) derived from a woman with Burkitt's lymphoma (BL) and acquired immunodeficiency syndrome that shared the same characteristic cytogenetic abnormalities as the patient's malignant cells. This cell line contained subclones that displayed an isotype switch from IgM to IgA1 and an accumulation of point mutations in the Vh region genes. Because these two features suggested an antigen-driven process, we began a search for the antigen responsible for the stimulation of the malignant B cells. Specifically, we hypothesized that because the patient's tumor had presented as a lymphomatous infiltration of the breast, the malignant B cells were recruited to this site because of the reactivity of their surface lg with breast tissue. A hybridoma (BRG-H) was obtained by fusing BRG-M cells (an IgM producing subclone of the BRG-P cell) with an appropriate cellular partner. The monoclonal antibody (BRG MoAb) produced by this hybridoma reacted strongly with two of five breast cancer cell lines and stained normal and malignant ductal epithelial cells on breast tissue sections. The antigen recognized by the BRG MoAb consisted of a single, minimally glycosylated polypeptide chain of 45 kD (p45). The BRG MoAb failed to react with a panel of human cell lines from different tissues, except for one cell line from a uterine cervical carcinoma. No reactivity was detected for a panel of exogenous antigens from various pathogens, including human immunodeficiency virus and self- antigens frequently recognized by polyspecific antibodies. Experiments were performed to investigate the functional consequences of the interaction of surface IgM with its specific ligand. Coculture of BRG-M cells with p45+, but not with p45-, breast cells caused apoptosis of BRG-M cells. The specificity of the interaction was shown by the observation that apoptosis was prevented by pretreatment of BRG-M cells with a monovalent F(ab′) fragment of rabbit IgG antibody to human mu chains. Moreover, only BRG-M cells, but not other BL cells, underwent apoptosis after exposure to p45+ breast cells. The interaction between the CD40 molecule expressed by BRG-M cells and its specific ligand (CD40L) prevented p45-induced cell apoptosis. Because this interaction mimics that occurring in vivo between T and B cells during immune responses, our data suggest that various events contributed to the emergence of the BL, in this particular patient, including antigenic stimulation possibly assisted by T-cell help.

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Ahn, Myung-Ju, HyeRyun Kim, James Chih-Hsin Yang, Ji-Youn Han, Jong Seok Lee, Maximilian J. Hochmair, Jacky Yu-Chung Li, et al. "Brigatinib (BRG) versus crizotinib (CRZ) in Asian versus non-Asian patients (pts) in the phase III ALTA-1L trial." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 9026. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.9026.

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9026 Background: We report an analysis of BRG vs CRZ in Asian vs non-Asian pts with ALK inhibitor–naive, ALK+ NSCLC from ALTA-1L (NCT02737501). Methods: Pts were randomized 1:1 to BRG 180 mg QD (7-day lead-in at 90 mg) or CRZ 250 mg BID. Primary endpoint: blinded independent review committee (BIRC)-assessed PFS (RECIST v1.1). Secondary efficacy endpoints: BIRC-assessed ORR, intracranial (i) ORR, and iPFS. Results: 275 pts were randomized; 108 Asian (BRG/CRZ, n = 59/49), 167 non-Asian (n = 78/89); median age: Asian, 55/56 y; non-Asian, 60/60 y. 32/24% of Asians vs 22/28% of non-Asians received prior chemotherapy for advanced disease; 36/33% vs 24/28% had baseline CNS metastases. As of 19 Feb 2018, median follow-up was 10.1/10.0 mo (BRG/CRZ) in Asians vs 11.0/9.0 mo in non-Asians, with 12 vs 20 PFS events in Asians and 24 vs 43 in non-Asians. In Asians, median BIRC-assessed PFS (mo) was not reached (NR; 95% CI 11.2–NR) with BRG vs 11.1 (9.2–NR) with CRZ (HR 0.41 [95% CI 0.20–0.86]; log-rank P= 0.0261); in non-Asians, BRG PFS was NR (NR) vs 9.4 (7.3–NR) with CRZ (HR 0.54 [0.33–0.90]; log-rank P= 0.0132) (Table). AE profile of each drug was similar in Asians vs non-Asians. Most common any-grade AEs (≥25%) in Asians in BRG arm: diarrhea; elevated blood CPK, ALT, and AST. Discontinuation due to AE (BRG/CRZ): 8.5/6.3% in Asian pts; 14.3/10.1% in non-Asian pts. Conclusions: BRG showed comparable improvement in PFS vs CRZ both in Asians and non-Asians in ALK inhibitor–naive ALK+ NSCLC. Clinical trial information: NCT02737501. [Table: see text]

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Shi, Xiaolan, Zijiao Chen, Yi Yang, and Su Yan. "Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management." Gastroenterology Research and Practice 2022 (September 12, 2022): 1–7. http://dx.doi.org/10.1155/2022/2642551.

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Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. However, lack of guidelines leads to simple cognition and even ignorance of this disease for clinicians. Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. Next, although recently there has been an increasing awareness among researchers in terms of the relevant factors for BRG, further studies involving large samples are still required to certify the relationship between them explicitly. Besides, researches have established that BRG is closely associated with the development of precancerous lesions and gastric cancer. Till now, there is still no golden standard for diagnosis of BRG. Nevertheless, advances in techniques, especially extensive applications of endoscopy and chemical analysis of reflux contents, have improved our ability to identify the occurrence of this disease as well as distinguishing physiological reflux from pathological reflux. Finally, it is fortunate for patients that more and more importance has been attached to the treatment of BRG. From lifestyle modification to drug therapy to surgery, all of them with the view of realizing symptomatic relief are employed for patients with BRG. In this review, we briefly evaluate this disorder based on the best available evidence, offering an overview of its complicated pathogenesis, diverse relevant factors, potential carcinomatous risk, modern diagnostic investigations, and effective therapeutic plans.

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Bazhenova, Lyudmila, J. Graeme Hodgson, Corey J. Langer, George R. Simon, Scott N. Gettinger, Sai-Hong Ignatius Ou, Karen L. Reckamp, et al. "Activity of brigatinib (BRG) in crizotinib (CRZ)-resistant ALK+ NSCLC patients (pts) according to ALK plasma mutation status." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 9065. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.9065.

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9065 Background: BRG is a potent and selective ALK inhibitor with preclinical and clinical activity against wild-type ALK and a broad range of mutants associated with clinical CRZ resistance, including G1202R. Herein we examine the association between BRG efficacy and ALK mutation status using plasma specimens from the initiation of BRG treatment (baseline [BL]) and the end of BRG treatment (EOT) in CRZ-resistant ALK+ NSCLC pts enrolled in the BRG Ph1/2 or pivotal Ph2 (ALTA) trials. Methods: Plasma samples were analyzed using the Resolution Bioscience ctDx Lung Panel v3.0. BRG activity was described using the confirmed objective response rate (cORR) (RECIST v1.1). Data are reported as of May 31, 2016 for the Ph1/2 (NCT01449461) and ALTA (NCT02094573) trials. Results: Of 291 CRZ-resistant ALK+ NSCLC pts enrolled in the Ph1/2 (N = 69) and ALTA (N = 222) trials, evaluable plasma samples were obtained from 67 pts at BL. cORR to BRG in these pts was 49% (33/67). An ALK fusion was detected in plasma in 45% (30/67) of these pts (cORR 57% [17/30]), of whom 33% (10/30) had secondary ALK mutations (cORR 50% [5/10]) and 67% (20/30) did not (cORR 60% [12/20]). Best responses in pts with secondary ALK mutations were: 2 CR (ALK amplification [Amp] copy number [CN] = 10; T1151M); 3 PR (L1196M; E1408V; Amp CN = 6); 4 SD (L1196M; E1419K; F1174C; C1156Y+S1206F+G1269A); 1 PD (T1151R+C1156Y+E1161D+F1174L). Of 67 pts with evaluable plasma at BL, 35 discontinued BRG therapy, of whom 20 had evaluable samples collected at EOT. No new mutations were detected at EOT in 75% (15/20) of pts. Complex mutation patterns were associated with resistance in the remaining 25% (5/20): High-level ALK-Amp (CN = 58); ALK-Amp (CN = 14)+MET-Amp (CN = 6); ALK-S1206F+S1206C+Amp (CN = 6); ALK-G1202R+L1196M+L1198Q; ALK-G1202R+BRAF-V600E+KRAS-G12D. Conclusions: ALK fusions were detected in plasma in < 50% of CRZ-resistant ALK+ NSCLC pts. BRG had substantial activity in ALK fusion–positive pts with a range of CRZ-resistance mutations. Neither primary nor secondary resistance to BRG was associated with any single plasma ALK mutation. The therapeutic implications of complex secondary resistance patterns associated with BRG require further exploration. Clinical trial information: NCT01449461, NCT02094573.

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Chen, Qing-Hu, and Xiao Hu. "Effect of Disorder on Driven Vortex Matter in High-Tc Superconductors." International Journal of Modern Physics B 17, no. 18n20 (August 10, 2003): 3433–35. http://dx.doi.org/10.1142/s0217979203021149.

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We performed large-scale simulations in the current-driven three-dimensional frustrated anisotropic XY model in the presense of point-like defects with resistively-shunted junction dynamics. A moving Bragg (BrG) glass is observed applying the current in the equilibrium BrG state. The first-order phase transition from the moving BrG to the moving smectic is clarified. The effect of disorder become weak once the vortex matter is set in motion.

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Buscarlet, Manuel, Veneta Krasteva, Lena Ho, Camille Simon, Josée Hébert, Brian Wilhelm, Gerald R. Crabtree, Guy Sauvageau, Pierre Thibault, and Julie A. Lessard. "Essential role of BRG, the ATPase subunit of BAF chromatin remodeling complexes, in leukemia maintenance." Blood 123, no. 11 (March 13, 2014): 1720–28. http://dx.doi.org/10.1182/blood-2013-02-483495.

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Henderson, Angus, Adele Holloway, Raymond Reeves, and David John Tremethick. "Recruitment of SWI/SNF to the Human Immunodeficiency Virus Type 1 Promoter." Molecular and Cellular Biology 24, no. 1 (January 1, 2004): 389–97. http://dx.doi.org/10.1128/mcb.24.1.389-397.2004.

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ABSTRACT Following human immunodeficiency virus type 1 (HIV-1) integration into the host cell's genome, the 5′ long terminal repeat (LTR) is packaged into a highly specific chromatin structure comprised of an array of nucleosomes positioned with respect to important DNA sequence elements that regulate the transcriptional activity of the provirus. While several host cell factors have been shown to be important for chromatin remodeling and/or basal transcription, no specific mechanism that relieves the transcriptional repression imposed by nuc-1, a positioned nucleosome that impedes the start site of transcription, has been found. Since phorbol esters cause the rapid disruption of nuc-1 and markedly stimulate HIV-1 transcription, we looked for protein factors that associate with this region of the HIV-1 promoter in a phorbol-ester-dependent manner. We report here that ATF-3, JunB, and BRG-1 (the ATPase subunit of the 2-MDa human chromatin remodeling machine SWI/SNF) are recruited to the 3′ boundary of nuc-1 following phorbol myristate acetate stimulation in Jurkat T cells. Analysis of the recruitment of BRG-1 in nuclear extracts prepared from Jurkat T cells and reconstitution of an in vitro system with purified components demonstrate that ATF-3 is responsible for targeting human SWI/SNF (hSWI/SNF) to the HIV-1 promoter. Importantly, this recruitment of hSWI/SNF required HMGA1 proteins. Further support for this conclusion comes from immunoprecipitation experiments showing that BRG-1 and ATF-3 can exist together in the same complex. Although ATF-3 clearly plays a role in the specific targeting of BRG-1 to the HIV-1 promoter, the maintenance of a stable association between BRG-1 and chromatin appears to be dependent upon histone acetylation. By adding BRG-1 back into a BRG-1-deficient cell line (C33A cells), we demonstrate that trichostatin A strongly induces the 5′-LTR-driven reporter transcription in a manner that is dependent upon BRG-1 recruitment.

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Camidge, D. Ross, Huifeng Niu, Hye Ryun Kim, James Chih-Hsin Yang, Myung-Ju Ahn, Jacky Yu-Chung Li, Maximilian Hochmair, et al. "Correlation of baseline molecular and clinical variables with ALK inhibitor efficacy in ALTA-1L." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 9517. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.9517.

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9517 Background: Efficacy of ALK TKIs in patients (pts) with ALK+ non-small cell lung cancer (NSCLC) varies. We evaluated the impact of EML4-ALK fusion variants and other baseline (BL) molecular and clinical variables on clinical efficacy of brigatinib (BRG) vs crizotinib (CRZ) as first ALK TKI therapy in pts with ALK+ NSCLC in the phase 3 ALTA-1L (NCT02737501) trial. Methods: Plasma samples were collected at screening for molecular genetic analysis of ALK and other genes implicated in NSCLC by next-generation sequencing. Exploratory analyses were performed to identify associations of clinical outcomes with oncogenic alterations including ALK fusion variants and TP53 status. Results: 124 BL samples were collected from 136 BRG-treated pts and 127 from 137 CRZ-treated pts. Pts with plasma samples were representative of the intent-to-treat population. BL ALK fusion detection rate was 52% (65/124) and 54% (68/127) in the BRG and CRZ arms, respectively, of which 83% (54/65) and 93% (63/68) were EML4-ALK fusions. In pts with detectable EML4-ALK fusions, the three predominant EML4-ALK fusion variants (V1, V2, V3) were equally distributed between arms; V1 and V3 were most prevalent (BRG/CRZ: V1, 42%/47%; V3, 42%/33%) but V1 was more frequent than V3 in pts without BL brain metastasis (47% vs 36%) or prior chemotherapy (45% vs 35%). Gender and age did not impact variant type. BRG showed higher ORR and improved mPFS vs CRZ in all variant subgroups; pts with V3 had poorer PFS compared with V1 and V2 regardless of treatment (Table). In pts with V3, BRG showed significantly improved PFS (HR=0.273, 95% CI 0.125, 0.597) and higher ORR (84% vs 67%) vs CRZ. TP53 mutation was detected in 30% (37/124) of pts in BRG arm and 26% (33/127) in CRZ arm. In pts with detectable ALK fusion, TP53 mutation showed poorer PFS in both arms than nonmutant/undetected cases (Table). BRG had better ORR and PFS vs CRZ in pts regardless of TP53 mutation status. Additional analyses of BL variables are ongoing. Conclusions: EML4-ALK fusion variant 3 and TP53 mutation were identified as poor prognosis biomarkers in ALK+ NSCLC. BRG demonstrated better efficacy than CRZ as first-line therapy in pts regardless of EML4-ALK fusion variant and TP53 mutation status. These findings may help define areas of greatest unmet need. Clinical trial information: NCT02737501 . [Table: see text]

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Wee, G., D. B. Koo, J. S. Kim, B. S. Song, J. S. Park, X. L. Jin, Y. Y. Lee, Y. M. Han, and K. K. Lee. "156 DIFFERENTIAL REORGANIZATION OF HISTONE ACETYLATION THROUGH ATP-DEPENDENT REMODELING FACTOR DURING PRONUCLEAR FORMATION IN PORCINE ZYGOTIC CHROMATINS." Reproduction, Fertility and Development 19, no. 1 (2007): 195. http://dx.doi.org/10.1071/rdv19n1ab156.

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ATP-dependent remodeling complexes and histone acetyltransferase/deacetylase complexes in chromatin modification can be characterized by the use of energy from ATP hydrolysis or covalent modification. But they have similar functions during the transcriptional process. After fertilization, histone acetylation in paternal and maternal chromatin is reprogrammed to obtain transcriptional activity during chromatin remodeling such as decondensation. However, these mechanisms in zygotic chromatin are poorly understood. In the present study, the reorganization process of histone H4 acetylation after fertilization was investigated through co-localization in the nucleus of ATP-dependent remodeling factors and histone acetyltransferases during parental chromatin decondensation. The molecules were monitored by immunofluorescence analysis with specific antibodies directed against AcH4K5, HAT1, P300, Tip60, Brg-1, and Mi-2. Fluorescence signals of Brg-1 and Mi-2 in porcine embryonic fibroblasts and HeLa cells co-localized with chromatin during interphase and M phase, although the Mi-2 signal existed around chromosomes at metaphase. However, Brg-1 and Mi-2 in porcine oocytes did not interact with chromosomes during meiosis, despite their existence in the oocyte cytoplasm. At 6 h after fertilization, signals of Brg-1 and Mi-2 were observed in most parental chromatin and remained until syngamy of the pronuclear stage. In histone acetylation and chromatin remodeling, acetylation of H4K5 was generated from sperm chromatin at 4 h after fertilization and preceded the appearance of Brg-1. Additionally, HAT1 showed stronger intensities compared with P300 and Tip60, correlating with acetylated-H4K5, and also appeared earlier than Brg-1. In contrast to that in sperm chromatin, Brg-1 in maternal chromatin anteceded HAT1. Consequently, paternal chromatin remodeling was completed after histone acetylation, but maternal chromatin remodeling was preceded by histone acetylation. Our findings indicate that paternal and maternal chromatin undergo differential remodeling and reprogramming during pronuclear formation, suggesting that gene expression in the chromatin of each parent may be regulated separately.

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Vaštakaitė-Kairienė, Viktorija, Aušra Brazaitytė, Jurga Miliauskienė, Rūta Sutulienė, Kristina Laužikė, Akvilė Viršilė, Giedrė Samuolienė, and Erik S. Runkle. "Photon Distribution of Sole-Source Lighting Affects the Mineral Nutrient Content of Microgreens." Agriculture 12, no. 8 (July 23, 2022): 1086. http://dx.doi.org/10.3390/agriculture12081086.

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In the study, we cultivated basil, beet, and mustard microgreens under different lighting treatments from light-emitting diodes (LEDs) and evaluated the contents of mineral nutrients. Microgreens grew under blue 447, red 638 and 665, far-red 731 nm LEDs, or the same spectrum but with partial substitution of 638 nm red with green 520 (BRG), yellow 595 (BRY), or orange 622 nm (BRO) LEDs (16 h photoperiod; total photon flux density of 300 μmol m −2 s −1). BRG, BRY, or BRO lighting had distinct effects on mineral contents among the microgreen species. BRG increased the content of mineral nutrients, especially in mustard and beet. In all microgreens, Ca and P were associated with BRG; in beet and mustard, Zn and Mg were associated with BRG; in basil, Zn was associated with BRY and Mg with BRO treatments. A broader photon spectrum increased Fe (up to 2.9–fold), K:Ca, P:Mg, and P:Zn in basil, and Fe:Zn in microgreens. We conclude that the partial replacement of red with green light was the most effective at enhancing the mineral nutrient content of microgreens, although responses varied among the crops studied.

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Paradis, Suzanne, John Ludden, and Léopold Gélinas. "Evidence for contrasting compositional spectra in comagmatic intrusive and extrusive rocks of the late Archean Blake River Group, Abitibi, Quebec." Canadian Journal of Earth Sciences 25, no. 1 (January 1, 1988): 134–44. http://dx.doi.org/10.1139/e88-013.

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The Flavrian pluton is a sill-shaped intrusion in the Blake River Group (BRG) volcanic rocks in the Noranda region of the Abitibi greenstone belt. The pluton is dominated by trondhjemites and tonalites, with minor peripheral quartz gabbro and hybrid phases. The BRG volcanic rocks consist of a bimodal suite of basalt–andesite and rhyolite. The Flavrian trondhjemites are geochemically identical to the rhyolitic lavas of the BRG (SiO2 ≥ 72%, La/Sm = 3.4, La/Yb = 3.6, Zr/Y = 3.9, Y/Nb = 3.1), and the Flavrian gabbroic and dioritic rocks are identical to the BRG basalts and andesites (SiO2 < 58%, La/Sm = 3.0, La/Yb = 5.5, Zr/Y = 4.2, Y/Nb = 3.3). However, the tonalitic rocks of the Flavrian pluton have no extrusive equivalents in the BRG. The different compositional spectra of the extrusive and intrusive rocks are interpreted as being a result of a transition in magma-chamber evolution from a zoned open system that was active during the evolution of the volcanic rocks to closed-system plutonic crystallization. The latter destroyed the compositional bimodality of the magma chamber and resulted in the evolution of intermediate compositions (tonalites) generated by both fractional crystallization and magma mixing.

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MARTÍN-DELGADO, MIGUEL A., and GERMÁN SIERRA. "ANALYTIC FORMULATIONS OF THE DENSITY MATRIX RENORMALIZATION GROUP." International Journal of Modern Physics A 11, no. 17 (July 10, 1996): 3145–74. http://dx.doi.org/10.1142/s0217751x96001516.

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We present two new analytic formulations of the density matrix renormalization group (DMRG) method. In these formulations we combine the block renormalization group (BRG) procedure with the variational and Fokker-Planck methods. The BRG method is used to reduce the lattice size while the latter are used to construct approximate target states to compute the block density matrix. We apply our DMRG methods to the Ising model in a transverse field (ITF model) and compute several of its critical properties, which are then compared with the old BRG results.

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Nam, Hyoung-Chul, Chang-Hyun Kim, and Soon-Man Kwon. "Contact Fatigue Life for RRG System." Journal of manufacturing engineering & technology 21, no. 1 (February 15, 2012): 95–101. http://dx.doi.org/10.7735/ksmte.2012.21.1.095.

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Anggraini, Rani Diah. "Difusi Inovasi Pengolahan Lahan Basah Tanpa Bakar di Kalimantan Tengah." Jurnal Penelitian Pers dan Komunikasi Pembangunan 24, no. 1 (May 30, 2020): 23–45. http://dx.doi.org/10.46426/jp2kp.v24i1.113.

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The haze disaster that hit the Central Kalimantan and surrounding areas in 2015 had a broad impact on various fields of life, such as economics, health, and education. The government prohibits land clearing by burning and launching a peat restoration program to prevent the occurrence of the smog haze again while restoring degraded peat ecosystems. However, the diffusion of innovations in peat restoration programs carried out by BRG in which there is PLTB program must deal with the habit of burning land that has been carried out for generations. The study about the process of diffusion of innovations in PLTB program in Central Kalimantan used a qualitative descriptive approach with a case study method. The face-to-face interpersonal communication channel is the main communication channel of the BRG in the process of diffusion of innovation in PLTB program and is considered the most effective. BRG maximizes the role of opinion leaders and change agents as a source of information. BRG also improved the function of Fasdes and established intensive communication with peatland farmers through the WhatsApp group to overcome uneven internet network constraints. Keywords: Peat Restoration, Land Processing without Burning, Diffusion of Innovations ABSTRAK Bencana kabut asap yang melanda wilayah Kalimantan Tengah dan sekitarnya pada tahun 2015 berdampak luas pada berbagai bidang kehidupan, seperti ekonomi, kesehatan, dan pendidikan. Pemerintah melarang pembukaan lahan dengan membakar dan mencanangkan program restorasi gambut untuk mencegah bencana kabut asap kembali terjadi sekaligus mengembalikan ekosistem gambut yang terdegradasi. Namun, difusi inovasi program restorasi gambut oleh BRG di mana terdapat program PLTB harus berhadapan dengan kebiasaan membakar lahan yang telah dilakukan masyarakat secara turun-temurun. Penelitian tentang proses difusi inovasi program PLTB di Kalimantan Tengah ini menggunakan pendekatan deskriptif kualitatif dengan metode studi kasus. Saluran komunikasi interpersonal secara tatap muka menjadi saluran komunikasi utama BRG dalam proses difusi inovasi program PLTB dan dinilai paling efektif. BRG memaksimalkan peran pemuka pendapat dan agen-agen perubahan sebagai sumber informasi. BRG juga meningkatkan fungsi Fasdes dan menjalin komunikasi intensif dengan petani-petani lahan gambut melalui grup WhatsApp untuk mengatasi kendala jaringan internet yang belum merata. Kata kunci: Restorasi Gambut, Pengolahan Lahan Tanpa Bakar, Difusi Inovasi

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Ling, Wei, Yi Huang, Jia-Hua Xu, Yang Li, Yan-Mei Huang, Hai-Bing Ling, Yi Sui, and Hai-Lu Zhao. "Consistent Efficacy of Wendan Decoction for the Treatment of Digestive Reflux Disorders." American Journal of Chinese Medicine 43, no. 05 (January 2015): 893–913. http://dx.doi.org/10.1142/s0192415x15500524.

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Gastroesophageal reflux disease (GERD) and bile reflux gastritis (BRG) are common gastrointestinal (GI) disorders with unmet medical needs. Traditional Chinese medicine has long been used for the treatment of GERD and BRG whereas the ginger-containing formula Wendan decoction (WDD) targets homeostatic disturbances characterized by "reflux" and "gut-juice exposure" problems. Here we used WDD as a therapeutic tool to unravel the common pathogenesis of GI reflux disorders. Control clinical trials reporting the WDD-treated patients with GERD and BRG were included in this systematic review and meta-analysis. Outcome measurements were clinical efficacy defined by symptom relief with normal GI endoscopy, radiology, and pathology. Eventually, 33 studies involved 3253 participants (1351 vs. 1035 of the BRG in 20 publications, 449 vs. 418 of the GERD in 13 studies, and 194 vs. 159 of relapse rate in 6 trials). Pooled data showed a consistent therapeutic efficacy of WDD on BRG (OR = 6.00, 95%C = 4.68–7.69) and GERD (OR = 4.39, 95%CI = 2.72–7.07). The relapse rate was 12.4% for WDD, significantly lower than 44.0% for conventional therapies (OR = 0.14, 95%CI = 0.08–0.26). The consistent therapeutic efficacy of the single TCM formula on GERD and BRD indirectly indicates reflux as a common pathogenesis in reflux-associated GI disorders.

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Omo-Ogboi, A. C., W. Wang, and B. Zhao. "The first case of BRG (SMARCA4)/INI Deficient Tracheal Carcinoma: A Case Report and Review of the Literature." American Journal of Clinical Pathology 156, Supplement_1 (October 1, 2021): S150—S151. http://dx.doi.org/10.1093/ajcp/aqab191.320.

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Abstract Introduction/Objective Primary tumors of the trachea are rare, they account for less than 0.1% of tumors in humans. In adults, 90% of primary tracheal tumors are malignant, with squamous cell carcinoma and adenoid cystic carcinoma accounting for two-thirds, with other forms occurring less frequently. The BRG (SMARCA4)/INI deficient tumor is a relatively new defined entity which is recently introduced in the WHO Classification of Tumors, 5th edition, 2021. The gene SMARCA4 is located at 19p13. Loss of SMARCA4 has been reported in several aggressive tumors with high- grade undifferentiated rhabdoid morphology but has not been reported in the trachea. Hence, we report the first case of BRG (SMARCA4)/ INI deficient tracheal carcinoma. Methods/Case Report We present a 60-year-old male with a history of tobacco abuse, shortness of breath, and a tracheal mass on chest imaging. Bronchoscopy was performed and showed a fleshy friable lesion at the anterior trachea with evidence of blood dripping into the distal airways. Results (if a Case Study enter NA) Microscopic examination showed a high grade, poorly differentiated carcinoma with tumor necrosis, high mitotic counts, and marked nuclear pleomorphism. Immunohistochemical stains were performed. The tumor cells were strongly and diffusely positive for CK-7 and weakly positive for synaptophysin, negative for pan-cytokeratin, TTF-1, CK-20, p40, CK5/6, and chromogranin. Then BRG (SMARCA4) and INI 1 (BAR47) were performed and showed negative staining on BRG expression, while INI 1 is intact (nuclear expression). These features are consistent with BRG (SMARCA4)/ INI deficient carcinoma. Conclusion BRG (SMARCA4)/ INI deficient carcinoma is a new entity in the trachea, which is very aggressive with a poor prognosis. Targeted therapy or clinical trials may be available as additional cases are diagnosed in the future.

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Purdy, Graeme M., Marina A. James, Paige K. Wakefield, Rachel J. Skow, Sean Van Diepen, Linda E. May, Margie H. Davenport, and Craig D. Steinback. "Maternal cardioautonomic responses during and following exercise throughout pregnancy." Applied Physiology, Nutrition, and Metabolism 44, no. 3 (March 2019): 263–70. http://dx.doi.org/10.1139/apnm-2018-0397.

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Blood pressure regulation during pregnancy is poorly understood. Cardiovagal baroreflex gain (BRG) is an important contributor to blood pressure regulation through its influence on heart rate. Heart rate fluctuations occur in response to various physiological stimuli and can be measured using heart rate variability (HRV). It is unclear how these mechanisms operate during pregnancy, particularly with regard to exercise. We examined BRG and HRV prior to, during, and following prenatal exercise. Forty-three pregnant (n = 10 first trimester (TM1), n = 17 second trimester (TM2), n = 16 third trimester (TM3)) and 20 nonpregnant (NP) women underwent an incremental peak exercise test. Beat-by-beat blood pressure (photoplethysmography) and heart rate (lead II electrocardiogram) were measured throughout. BRG (the slope of the relationship between fluctuations in systolic blood pressure and the R–R interval) and HRV (root mean square of the successive differences; RMSSD) were assessed at rest, during steady-state exercise (EX), and during active recovery. BRG decreased with gestation and was lower in the TM3 group than in the NP group (17.9 ± 6.9 ms/mm Hg vs 24.8 ± 7.4 ms/mm Hg, p = 0.017). BRG was reduced during EX in all groups. Resting HRV (RMSSD) also decreased with gestation and was lower in the TM3 group than in the NP group (29 ± 17 ms vs 48 ± 20 ms, p < 0.001). RMSSD was blunted during EX in all groups compared with rest. During active recovery, RMSSD was further blunted compared with EX in the NP group but not during pregnancy (TM1, TM2, and TM3). Compared with the nonpregnant controls, the pregnant women had lower BRG and HRV at rest, but comparable cardioautonomic control during both exercise and active recovery following peak exercise.

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Kim, Hyung Joong, Tae Kyu Oh, Yoon Hee Kim, Jaesun Lee, Joo Myung Moon, Yong Sun Park, and Chang Min Sung. "Pharmacokinetics of Ginsenoside Rb1, Rg3, Rk1, Rg5, F2, and Compound K from Red Ginseng Extract in Healthy Korean Volunteers." Evidence-Based Complementary and Alternative Medicine 2022 (January 24, 2022): 1–10. http://dx.doi.org/10.1155/2022/8427519.

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Individual differences in ginsenoside pharmacokinetics following ginseng administration in humans are still unclear. We aimed to investigate the pharmacokinetic properties of various ginsenosides, including Rb1, Rg3, Rg5, Rk1, F2, and compound K (CK), after a single oral administration of red ginseng (RG) and bioconverted red ginseng extract (BRG). This was a randomized, open-label, single-dose, single-sequence crossover study with washout every 1 week, and 14 healthy Korean men were enrolled. All subjects were equally assigned to two groups and given RG or BRG capsules. The pharmacokinetic parameters of ginsenosides were measured from the plasma drug concentration–time curve of individual subjects. Ginsenosides Rg3, Rk1 + Rg5, F2, and CK in the BRG group showed a higher Cmax, AUC(0–t), and AUC(0–∞) and shorter Tmax (for CK) than those in the RG group. These results suggest that BRG may lead to a higher absorption rate of bioactive ginsenosides. This study provides valuable information on the pharmacokinetics of various bioactive ginsenosides, which is needed to enhance the therapeutic efficacy and pharmacological activity of ginseng.

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Guan, Hua-qin, Cheng Hang, Ming Zhang, Li-Yan Yuan, and Yan-jun Ding. "Effect of Individualized Cardiac Rehabilitation on Cardiac Function, Time Consumption, and Quality of Life in Patients After CABG." Heart Surgery Forum 26, no. 1 (February 10, 2023): E074—E080. http://dx.doi.org/10.1532/hsf.5249.

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Background: To investigate the effect of individualized cardiac rehabilitation (CR) on cardiac function, time consumption, and quality of life (QoL) in post-CABG patients. Methods: Two different CR strategy: basic rehabilitation and individualized rehabilitation was designed. The patients were screened and randomized into the two groups: the basic rehabilitation group (BRG) and individualized rehabilitation group (IRG). Data, such as clinical characteristics, LVEF, 6MWD (6-min walk distance), BNP, LVEDD (left ventricular end diastolic dimension), SF-36 score, and time consumption were collected and recorded. Results: There was no difference between the IRG and BRG patients in the clinical characteristics. The 6MWD and LVEF on post-op significantly were higher, while BNP and LVEDD significantly was lower in the IRG than in BRG. The time to first out-of-bed activity, ICU stay time, and post-op hospital stay time of the IRG in post-op was significantly shorter than BRG. The IRG patients scored significantly higher on the SF-36. Conclusion: Individualized CR is safe and can reduce the time consumption and improve the cardiac function and QoL of patients undergoing CABG.

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Tiseo, Marcello, Sanjay Popat, Scott N. Gettinger, Solange Peters, Jeff Haney, David Kerstein, and D. Ross Camidge. "Design of ALTA-1L (ALK in lung cancer trial of brigatinib in first-line), a randomized phase 3 trial of brigatinib (BRG) versus crizotinib (CRZ) in tyrosine kinase inhibitor (TKI)-naive patients (pts) with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): TPS9098. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.tps9098.

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TPS9098 Background: BRG is an investigational, next-generation ALK inhibitor with potent preclinical activity against rearranged ALK and CRZ-resistant mutants. In an ongoing phase 1/2 trial, BRG has shown promising intracranial and whole-body activity in ALK+ NSCLC pts with or without prior CRZ therapy ( Lancet Oncol. 2016;17:1683-96). In an ongoing pivotal randomized phase 2 trial (ALTA) evaluating 2 BRG regimens (90 mg qd and 180 mg qd with a 7-d lead-in at 90 mg), BRG has shown substantial objective response rates (ORRs) and robust progression-free survival (PFS) in pts with CRZ-resistant ALK+ NSCLC, particularly at 180 mg (with lead-in), and acceptable safety ( J Thorac Oncol. 2017;12:S612-3). Based on these results, the ALTA-1L trial was designed to assess the efficacy and safety of BRG vs CRZ in pts with advanced ALK+ NSCLC naive to TKI therapy (including ALK inhibitors). Methods: ALTA-1L (NCT02737501) is an open-label, multicenter, randomized phase 3 trial. Pts (≥18 y of age) are required to have locally advanced or metastatic ALK+ NSCLC, no prior TKI therapy, and ≤1 prior systemic anticancer regimen in the advanced setting. Approximately 270 pts will be stratified by presence of brain metastases at baseline and prior chemotherapy (yes/no) and randomized 1:1 to receive oral BRG (180 mg qd with a 7-d lead-in at 90 mg) or CRZ (250 mg bid). The primary endpoint is PFS per RECIST v1.1 assessed by a blinded independent review committee (BIRC); secondary endpoints include ORR, duration of response, overall survival, safety/tolerability, pt-reported outcomes, and intracranial ORR/PFS. The primary endpoint will be analyzed with the Kaplan-Meier method and a 2-sided stratified log-rank test after 198 events; 2 interim analyses are planned after approximately 50% and 75% of expected events. CRZ-treated pts may cross over to BRG (180 mg [with lead-in]) after BIRC-assessed disease progression. ALTA-1L was initiated in April 2016; 150 sites are planned in North America, Europe, and the Asia-Pacific region. 97 pts were enrolled as of February 6, 2017. Clinical trial information: NCT02737501.

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NIE, QING-MIAO, MENG-BO LUO, QING-HU CHEN, and XIAO HU. "DISORDER DRIVEN MELTING OF MOVING VORTEX MATTER IN LAYERED SUPERCONDUCTORS." International Journal of Modern Physics B 18, no. 17n19 (July 30, 2004): 2476–79. http://dx.doi.org/10.1142/s0217979204025531.

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The current-driven three-dimensional frustrated anisotropic XY model with strong disorder is simulated to model the moving vortex matter in layered superconductors. The equilibrium disordered state can be driven to a moving Bragg glass (BrG) by applying an external current. As the pinning strength increases, the moving BrG can melt into a moving smectic via a first-order phase transition.

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Reckamp, Karen L., Joseph Lee, Joice Huang, Irina Proskorovsky, William Reichmann, Mira Krotneva, David Kerstein, and Hui Huang. "Matching-adjusted indirect comparison (MAIC) of relative efficacy for brigatinib vs. ceritinib and alectinib in crizotinib-resistant anaplastic lymphoma kinase (ALK+) non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e20675-e20675. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e20675.

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e20675 Background: Brigatinib (BRG), ceritinib (CER), and alectinib (ALEC) are second-generation ALK inhibitors developed for crizotinib (CRZ)-resistant ALK+ NSCLC. No randomized trial has directly compared the efficacy of these treatments. The goal of this analysis was to use an MAIC to indirectly compare progression-free survival (PFS) and overall survival (OS) for BRG vs CER and BRG vs ALEC in CRZ-resistant ALK+ NSCLC patients (pts). Methods: This analysis used pt-level data from arm B (180 mg qd with a 7-day lead-in at 90 mg, n=110) of the ALTA trial for BRG and published summary data from ASCEND-1/ASCEND-2 and NP28673 trials for CER and ALEC, respectively. PFS and OS curves from published data were digitized to generate virtual pt-level data for estimation of event rates. Pts in ALTA were assigned weights so that their weighted mean baseline characteristics matched baseline characteristics in each of ASCEND-1, ASCEND-2, and NP28673. Relative treatment effects pre- and post-matching were estimated using Cox proportional hazards models. Results: Prior to matching, baseline imbalances were noted in ECOG PS 2, prior chemotherapy, Asian race, smoking status, and best prior response to CRZ among trials. Weighting reduced effective sample sizes (ESSs) for ALTA pts in the matched comparisons. Relative efficacy results were robust and did not appreciably change after adjusting for the prognostic factors (Table 1). Conclusions: Both before and after matching, BRG had significantly longer PFS compared to CER and ALEC, significantly longer OS than CER, and a trend toward longer OS than ALEC. [Table: see text]

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Bazhenova, Lyudmila, Scott N. Gettinger, Corey J. Langer, Ravi Salgia, Kathryn A. Gold, Rafael Rosell, Alice Tsang Shaw, et al. "Brigatinib (BRG) in patients (pts) with ALK+ non-small cell lung cancer (NSCLC): Updates from a phase 1/2 trial." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e20682-e20682. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e20682.

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e20682 Background: The investigational next-generation ALK inhibitor BRG has shown activity in ALK+ NSCLC pts in a phase 1/2 trial; here, we provide updated data with longer follow-up. Methods: In this ongoing phase 1/2, single-arm, open-label, multicenter trial (NCT01449461), pts with advanced malignancies (including ALK+ NSCLC) received oral BRG (30–300 mg/d). Activity by RECIST v1.1 in ALK+ NSCLC pts and safety in all pts are shown. Results: 58% (79/137) pts had ALK+ NSCLC, with median age 54 y; of these, 90% (71/79) had received crizotinib (CRZ). As of May 31, 2016, 41% (32/79) ALK+ NSCLC pts continued to receive BRG; median treatment duration was 20.0 mo (1 d–47.4 mo). The table shows efficacy in CRZ-treated pts; median overall survival was 47.6 mo (95% CI 21.4–47.6 mo). All 8 CRZ-naive pts had confirmed objective responses; median duration of response and progression-free survival (PFS) were not reached. In a post hoc analysis, 53% (95% CI 27%–79%; 8/15) ALK+ NSCLC pts with measurable baseline brain metastases had confirmed intracranial objective responses (last scan date: October 8, 2015). Median intracranial PFS in 46 evaluable ALK+ NSCLC pts with baseline brain metastases was 14.6 mo (95% CI 12.7–36.8 mo). Treatment-emergent adverse events (AEs) in ≥30% of all pts, mainly grade 1/2, were nausea 53%, fatigue 45%, diarrhea 42%, headache 35%, and cough 33%; serious treatment-emergent AEs in ≥5% of pts were pneumonia 7%, dyspnea 6%, and hypoxia 5%. 10% of pts (14/137) discontinued BRG due to an AE. Conclusions: BRG yielded substantial whole-body and intracranial activity in ALK+ NSCLC pts in this trial, with acceptable safety. These data informed design of the pivotal randomized phase 2 trial of BRG (90 mg qd or 180 mg qd [with lead-in]) in CRZ-refractory ALK+ NSCLC (ALTA). Clinical trial information: NCT01449461. [Table: see text]

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Gettinger, Scott N., Rudolf M. Huber, Dong-Wan Kim, Lyudmila Bazhenova, Karin Holmskov Hansen, Marcello Tiseo, Corey J. Langer, et al. "Brigatinib (BRG) in ALK+ crizotinib (CRZ)-refractory non-small cell lung cancer (NSCLC): Final results of the phase 1/2 and phase 2 (ALTA) trials." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 9071. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.9071.

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9071 Background: BRG is a kinase inhibitor approved for the treatment of patients (pts) with ALK+ metastatic NSCLC; specific details for BRG use vary by indication and country. We report long-term efficacy and safety results of the Phase 1/2 and Phase 2 (ALTA) trials of BRG. Methods: The Phase 1/2 study was a single-arm, open-label trial (NCT01449461) of BRG 30–300 mg/d in pts with advanced malignancies. ALTA (NCT02094573) randomized pts with CRZ-refractory ALK+ NSCLC to receive BRG at 90 mg qd (arm A) or 180 mg qd with 7-d lead-in at 90 mg (arm B). For the Phase 1/2 study, investigator assessments of confirmed objective response rate (cORR; RECIST v1.1), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety in pts with ALK+ NSCLC are reported. The primary endpoint of ALTA was cORR per investigator; secondary endpoints included cORR per independent review committee (IRC), DoR, PFS, and OS. Results: In the Phase 1/2 study, 137 pts received BRG; of these, 79 pts had ALK+ NSCLC (71/79 had prior CRZ; 28/79 received 180 mg qd [7-d lead-in at 90 mg]; 14/79 received 90 mg qd). In ALTA, 222 pts with CRZ-refractory ALK+ NSCLC were randomized (n = 112/110, arm A/B). At the end of the Phase 1/2 study (Feb 18, 2020), with median 27.7 mo follow-up (̃67 mo after last pt enrolled), 4 pts remained on BRG. At the end of ALTA (Feb 27, 2020), with median 19.6/28.3 mo follow-up in arm A/B (̃53 mo after last pt enrolled), 10/17 pts in arm A/B were still on treatment. Table shows efficacy results from final analyses with long-term follow-up. In ALTA, the IRC-assessed intracranial cORR in pts with measurable baseline brain metastases was 50% (13/26) in arm A and 67% (12/18) in arm B; Kaplan-Meier (KM) estimated median intracranial DoR was 9.4 mo (95% CI, 3.7, not reached [NR]) in arm A and 16.6 mo (3.7, NR) in arm B. With long-term follow-up, no new safety signals were identified. Treatment-emergent adverse events led to dose interruption (Phase 1/2: 59%; ALTA arm A/B: 49%/61%), dose reduction (13%; 8%/33%), or discontinuation (10%; 4%/13%). Conclusions: BRG showed sustained long-term activity, PFS, and manageable safety in pts with CRZ-refractory ALK+ NSCLC. The 180 mg/d dose after 7-d lead-in at 90 mg/d led to numerically higher median PFS and OS. Final results are similar to those reported for other approved ALK tyrosine kinase inhibitors in this setting. Clinical trial information: NCT01449461, NCT02094573. [Table: see text]

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Hahn, Sarah Joy, Angelika Brandt, and Moritz Sonnewald. "Annotated checklist and biodiversity analysis of benthic fauna at Sylt Outer Reef and Borkum Reef Ground (North Sea)." Check List 18, no. 3 (June 10, 2022): 593–628. http://dx.doi.org/10.15560/18.3.593.

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Benthic fauna caught by ring dredge and 2 m beam trawl at the NATURA 2000 Sylt Outer Reef (SAR) and Borkum Reef Ground (BRG) sites in the North Sea are examined in relation to the intensity of mobile bottom-trawling fisheries. Samples were taken from 33 stations in the two areas, and the collected benthic fauna, consisting of infauna, epifauna, and demersal fish was determined. A total of 123 species were found, consisting of the phyla Chordata, Mollusca, Arthropoda, Echinodermata, Annelida, Cnidaria, and Bryozoa, with Chordata and Mollusca being the most species-rich phyla. The species compositions of BRG and SAR are relatively clearly separated. There was greater species diversity at BRG, likely due to lower fishing pressure from mobile bottom trawling than at SAR. Long-term data acquisition and analysis will be needed to visualize past and future changes in biodiversity

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Ahn, Myung-Ju, D. Ross Camidge, Marcello Tiseo, Karen L. Reckamp, Karin Holmskov Hansen, Sang-We Kim, Rudolf M. Huber, et al. "Brigatinib (BRG) in crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC): Updates from ALTA, a pivotal randomized phase 2 trial." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e20503-e20503. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e20503.

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e20503 Background: Most ALK+ NSCLC patients (pts) receiving CRZ eventually experience disease progression. Based on promising activity in a phase 1/2 trial, a randomized phase 2 trial of the ALK inhibitor BRG in pts with CRZ-refractory, advanced ALK+ NSCLC (ALTA; NCT02094573) was initiated. Responses and adverse events (AEs) varied with starting dose; therefore, ALTA was designed to evaluate 2 distinct BRG regimens. Methods: Pts were stratified by presence of baseline (BL) brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Primary endpoint was investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1. Results: In 222 pts (arm A/B, n=112/n=110), median age was 51/57 y; 71%/67% had brain metastases. As of May 31, 2016, 51%/56% (A/B) continued to receive BRG; median follow-up was 10.2/11.0 mo. Table shows efficacy. In pts with measurable BL brain metastases (A/B, n=26/n=18), confirmed intracranial ORR was 46%/67%. Most common treatment-emergent AEs (A/B) were: nausea 36%/43%, diarrhea 21%/39%, cough 23%/36%, headache 28%/30%, vomiting 28%/26%; grade ≥3 AEs included increased CPK 3%/10%, hypertension 6%/6%, pneumonia 3%/5%, increased lipase 5%/3%. A subset of pulmonary AEs with early onset (median: Day 2) occurred in 14/219 (6%) treated pts (3%, grade ≥3); 7/14 pts were successfully retreated. Dose reductions (8%/23%, A/B) and discontinuations (3%/10%) due to AEs were reported. Conclusions: BRG showed substantial activity, robust PFS, and acceptable safety at both dose levels, with numerically improved efficacy (particularly PFS and intracranial ORR) at 180 mg (with lead-in). Clinical trial information: NCT02094573. [Table: see text]

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Maugeri, Alessandro, Giovanni Enrico Lombardo, Laura Musumeci, Caterina Russo, Sebastiano Gangemi, Gioacchino Calapai, Santa Cirmi, and Michele Navarra. "Bergamottin and 5-Geranyloxy-7-methoxycoumarin Cooperate in the Cytotoxic Effect of Citrus bergamia (Bergamot) Essential Oil in Human Neuroblastoma SH-SY5Y Cell Line." Toxins 13, no. 4 (April 10, 2021): 275. http://dx.doi.org/10.3390/toxins13040275.

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The plant kingdom has always been a treasure trove for valuable bioactive compounds, and Citrus fruits stand out among the others. Bergamottin (BRG) and 5-geranyloxy-7-methoxycoumarin (5-G-7-MOC) are two coumarins found in different Citrus species with well-acknowledged pharmacological properties. Previously, they have been claimed to be relevant in the anti-proliferative effects exerted by bergamot essential oil (BEO) in the SH-SY5Y human neuroblastoma cells. This study was designed to verify this assumption and to assess the mechanisms underlying the anti-proliferative effect of both compounds. Our results demonstrate that BRG and 5-G-7-MOC are able to reduce the proliferation of SH-SY5Y cells, inducing apoptosis and increasing cell population in sub-G0/G1 phase. Moreover, we demonstrated the pro-oxidant activity of the two coumarins that increased reactive oxygen species and impaired mitochondrial membrane potential. From a molecular point of view, BRG and 5-G-7-MOC were able to modulate apoptosis related factors at both protein and gene levels. Lastly, we evaluated the synergistic effect of their combination, finding that the highest synergy was observed at a concentration ratio similar to that occurring in the BEO, supporting our initial hypothesis. Taken together, our results deepen the knowledge regarding the effect of BRG and 5-G-7-MOC in SH-SY5Y cells, emphasizing the relevance of their cooperation in achieving this effect.

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Ross, Pierre-Simon, Jean Goutier, Patrick Mercier-Langevin, and Benoît Dubé. "Basaltic to andesitic volcaniclastic rocks in the Blake River Group, Abitibi Greenstone Belt: 1. Mode of emplacement in three areas1This article is a companion paper to Ross et al. 2011. Basaltic to andesitic volcaniclastic rocks in the Blake River Group, Abitibi Greenstone Belt: 2. Origin, geochemistry, and geochronology. Canadian Journal of Earth Sciences, 48: this issue.2MRNF Contribution BEGQ 8439-2010/2011-1. Natural Resources Canada, Earth Science Sector Contribution 20100253." Canadian Journal of Earth Sciences 48, no. 4 (April 2011): 728–56. http://dx.doi.org/10.1139/e10-090.

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The Archean Blake River Group (BRG) of Ontario and Quebec is dominated by submarine mafic to intermediate lavas, with more restricted felsic volcanic rocks. Given the good quality of outcrop, and high level of preservation of some BRG rocks, the mafic to intermediate lavas were used in the 1970s and 1980s to better understand the evolution of massive and pillowed submarine flows, and their associated fragmental facies (pillow breccias, hyaloclastite). Potentially, the BRG could also represent a useful volcanic succession for the study of explosive submarine eruption products in the ancient record. Before this is possible, however, a regional inventory of the mafic to intermediate volcaniclastic units is needed to clarify their characteristics and origins. In this paper, we compare and contrast volcaniclastic rocks from three areas within the same formation of the northern BRG in Quebec: the Monsabrais area, the Lac Duparquet area, and the D’Alembert tuff area. Close examination reveals pronounced differences in terms of lateral continuity, thickness, grading, bedding, clast shapes, textures, etc. in the volcaniclastic rocks. These differences are interpreted to reflect vastly different emplacement processes, ranging from hyaloclastite generation as a result of self-fragmentation and lava contact with water (dominant in the Monsabrais and Lac Duparquet areas) to aqueous density currents likely fed directly by explosive submarine eruptions (dominant in the D’Alembert tuff).

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Miao, Ji, Sungsoon Fang, Jiyoung Lee, Clay Comstock, Karen E. Knudsen, and Jongsook Kim Kemper. "Functional Specificities of Brm and Brg-1 Swi/Snf ATPases in the Feedback Regulation of Hepatic Bile Acid Biosynthesis." Molecular and Cellular Biology 29, no. 23 (October 5, 2009): 6170–81. http://dx.doi.org/10.1128/mcb.00825-09.

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ABSTRACT Bile acid homeostasis is critical in maintaining health and is primarily regulated by the nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP). Bile acid-activated FXR indirectly inhibits expression of cholesterol 7α hydroxylase (CYP7A1), a key enzyme in conversion of cholesterol to bile acids, by induction of SHP. We recently demonstrated that SHP inhibits CYP7A1 transcription by recruiting chromatin-modifying cofactors, including Brm-Swi/Snf. Swi/Snf complexes contain either Brm or Brg-1 ATPases, and whether these subunits have distinct functions remains unclear. We have examined the role of these subunits in regulation of bile acid metabolism under physiological conditions by FXR and SHP. Brg-1 interacted with FXR and enhanced FXR-mediated transactivation of SHP, whereas Brm interacted with SHP and enhanced SHP-mediated repression of CYP7A1 and, interestingly, auto-repression of SHP. Chromatin immunoprecipitation and remodeling studies revealed that after treatment with FXR agonists, Brg-1 was recruited to the SHP promoter, resulting in transcriptionally active accessible chromatin, whereas Brm was recruited to both CYP7A1 and SHP promoters, resulting in inactive inaccessible chromatin. Our studies demonstrate that Brm and Brg-1 have distinct functions in the regulation of two key genes, CYP7A1 and SHP, within a single physiological pathway, feedback inhibition of bile acid biosynthesis, by differentially targeting SHP and FXR.

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Strobeck, Matthew W., David N. Reisman, Ranjaka W. Gunawardena, Bryan L. Betz, Steven P. Angus, Karen E. Knudsen, Timothy F. Kowalik, Bernard E. Weissman, and Erik S. Knudsen. "Compensation of BRG-1 Function by Brm." Journal of Biological Chemistry 277, no. 7 (November 21, 2001): 4782–89. http://dx.doi.org/10.1074/jbc.m109532200.

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Burgos, José, Aitor Viribay, Diego Fernández-Lázaro, Julio Calleja-González, Josefa González-Santos, and Juan Mielgo-Ayuso. "Combined Effects of Citrulline Plus Nitrate-Rich Beetroot Extract Co-Supplementation on Maximal and Endurance-Strength and Aerobic Power in Trained Male Triathletes: A Randomized Double-Blind, Placebo-Controlled Trial." Nutrients 14, no. 1 (December 23, 2021): 40. http://dx.doi.org/10.3390/nu14010040.

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Citrulline (CIT) and nitrate-rich beetroot extract (BR) are ergogenic aids and nitric oxide (NO) precursors. In addition, both supplements seem to have other actions at the level of muscle metabolism that can benefit strength and aerobic power performance. Both supplements have been studied in numerous investigations in isolation. However, scientific evidence combining both supplements is scarce, and to the best of the authors’ knowledge, there is no current study of endurance athletes. Therefore, the main purpose of this study was to determine the effect of 9 weeks of CIT plus BR supplementation on maximal and endurance-strength performance and aerobic power in male triathletes. This study was a randomized double-blind, placebo-controlled trial where participants (n = 32) were randomized into four different groups: placebo group (PLG; n = 8), CIT plus BR group (CIT- BRG; 3 g/kg/day of CIT plus 3 mg/kg/day of nitrates (NO3−); n = 8), CIT group (CITG; 3 g/kg/day; n = 8) and BR group (BRG; 3 mg/kg/day of NO3−; n = 8). Before (T1) and after 9 weeks (T2), four physical condition tests were carried out in order to assess sport performance: the horizontal jump test (HJUMP), handgrip dynamometer test, 1-min abdominal tests (1-MAT) and finally, the Cooper test. Although, no significant interactions (time × supplementation groups) were found for the strength tests (p > 0.05), the CIT- BRG supplementation presented a trend on HJUMP and 1-MAT tests confirmed by significant increase between two study moments in CIT-BRG. Likewise, CIT-BRG presented significant interactions in the aerobic power test confirmed by this group’s improve estimated VO2max during the study with respect to the other study groups (p = 0.002; η2p = 0.418). In summary, supplementing with 3 g/day of CIT and 2.1 g/day of BR (300 mg/day of NO3−) for 9 weeks could increase maximal and endurance strength. Furthermore, when compared to CIT or BR supplementation alone, this combination improved performance in tests related to aerobic power.

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Herndler-Brandstetter, Dietmar, Till Strowig, and Richard Flavell. "Development of a humanized mouse model to study human immune cell responses in vivo (P1468)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 60.17. http://dx.doi.org/10.4049/jimmunol.190.supp.60.17.

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Abstract Humanized mice hold great promise for modeling and studying human diseases in vivo, and to enable vaccine testing. Transplantation of human hematopoietic stem cells into immunocompromised newborn mice allows the development of a human immune system in vivo. NOD scid γc-/- (NSG) and Balb/c Rag2-/- γc-/- (BRG) mice are the most commonly used strains. However, some limitations have restricted the utility of humanized mice in translational research. In particular, the development and survival of human T cells and NK cells is suboptimal. We have therefore generated a human signal regulatory protein alpha (SIRPα) knock-in mouse, which prevents phagocytosis of human cells by mouse myeloid cells. We demonstrate that BRG Sirpα mice have an increased survival of human naïve CD8 and CD4 T cells, and NK cells in the periphery compared to NSG mice. The BRG Sirpα mice, together with human MHC and cytokine knock-in mice will thus be a crucial step towards a better environment for human immune cells in the mouse host to study human antigen-specific immune responses in vivo.

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Zulfan, Zulfan, Herawati Latif, Cut Aida Fitri, and Evi Aswita. "Effect of Feeding Quails with Mixture Feeds Composed of Crab Waste Meal, Leubim Fish Waste Meal, and Broken Rice Grains as Partly Substitution of Commercial Diet on Egg Quality." ANIMAL PRODUCTION 22, no. 2 (December 16, 2020): 82–91. http://dx.doi.org/10.20884/1.jap.2020.22.2.50.

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In rearing quails, many attempts have been done to reduce feed cost among other things by replacing partly commercial diet with numerous alternative feed sources such as crab waste meal (CWM), leubim fish (Canthidermis maculata) waste meal (LFWM), and broken rice grains (BRG). The purpose of this study was to determine the effect of using a mixture feeds composed of CWM + LFWM + BRG as a substitute for commercial laying chicken diets on the quality of quail eggs. This research was conducted at the Field Laboratory of Animal Husbandry and the Laboratory of Poultry Production Science, Syiah Kuala University. This study used 80 female quails (Coturnix-coturnix japonica) females aged 4 weeks. The treatment was feeding quails with the commercial diet of laying hen (324-1M) of which 0, 10, 20, and 30% of the diets was substituted by the mixture feeds composed of CWM + LFWM + BRG. The study was performed into block randomized design (BRD) consisting of 4 treatments and 4 replicate blocks. The blocks were established based on the different initial body weights of 4-week ages of female quails. Each treatment was an experimental unit consisting of 5 female quails each. The measured parameters were Yolk Index (YI), yolk color, Albumen Index (AI), eggshell thickness, and egg weight. The results of the study indicated that using up to 30% mixture feeds composed of 7,5% CWM + 9,1% LFWM + 13,4% BRG as a substitute for commercial laying chicken diets most significantly increased yolk index and yolk color of quail eggs. However, the albumen index, eggshell thickness, and egg weight were not significantly affected.

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Ou, Sai-Hong Ignatius, Marcello Tiseo, D. Ross Camidge, Myung-Ju Ahn, Rudolf M. Huber, Maximilian J. Hochmair, Sang-We Kim, et al. "Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC) and brain metastases in the pivotal randomized phase 2 ALTA trial." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e20502-e20502. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e20502.

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e20502 Background: The CNS is often a site of first disease progression in CRZ-treated ALK+ NSCLC. The ALTA trial is assessing BRG, an investigational next-generation ALK inhibitor, in pts with CRZ-refractory advanced ALK+ NSCLC, including pts with baseline brain metastases. Methods: In ALTA (NCT02094573), pts were stratified by presence of baseline brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Here, we show data for pts with baseline brain metastases. An independent review committee (IRC) assessed intracranial efficacy. Results: Of 222 pts (112 in arm A; 110 in arm B), 80 (71%)/74 (67%) in A/B had baseline brain metastases per investigators, with median age 49/55 y; 74%/76% had received chemotherapy. As of May 31, 2016, 51%/59% of these pts continued to receive BRG in A/B; median follow-up was 9.6/11.4 mo. Intracranial efficacy is shown in the table. Among these pts, most common treatment-emergent adverse events were: nausea 35%/46% (A/B), headache 30%/31%, vomiting 29%/31%, diarrhea 21%/38%, cough 25%/32%; grade ≥3: increased blood CPK 1%/12%, hypertension 4%/7%, increased lipase 4%/3%. Conclusions: BRG yielded substantial intracranial responses with robust iPFS and acceptable safety in ALK+ NSCLC pts with baseline brain metastases in ALTA. 180 mg (with lead-in) showed consistently improved intracranial efficacy compared with 90 mg. Clinical trial information: NCT02094573. [Table: see text]

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Nizmi, Yusnarida Eka, Yessi Olivia, Umi Oktyari Retnaningsih, M. Saeri, Ahmad Jama’an, and Alfajri Alfajri. "Economic ECONOMIC REVITALIZATION PROGRAM in ACHIEVING THE HAZE-FREE ASEAN TARGET 2020 by THE RIAU PROVINCE’S PEATLAND RESTORATION AGENCY." Berumpun: International Journal of Social, Politics, and Humanities 4, no. 2 (October 30, 2021): 167–83. http://dx.doi.org/10.33019/berumpun.v4i2.66.

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This study analyses the implementation of good governance principles for the economic revitalization program under Riau Province’s Badan Restorasi Gambut (Peatland Restoration Agency) supervision. One of the aims of this program is to support the haze-free ASEAN 2020 roadmap. Riau province is an area prone to forest fire disasters. Its peatland area, which is twice as large as Malaysia’s peatland, have a very high potential for damage due to forest fires. To mitigate the damages, BRG initiated the 3R program: Rewetting, Revegetation, and Revitalization. What makes this topic interesting is BRG emphasizes the aspects of economic empowerment of local communities to prevent further forest and peatland damages. To assess the implementation of BRG’s program, our research team conducted several interviews with representatives from Indonesia’s Ministry of Environment and Forestry, NGOs, academics, farmers, and villages’ facilitators who assisted local communities that received the BRG’s assistance packages. Our study shows that BRG’s economic revitalization program had succeeded in creating small scale economic activities such as honey industry, pineapple farming, and catfish farming. However, the ineffective coordination and communication between BRG and the local communities had prevented them from constructing an effective method to prevent future forest fires.

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Nizmi, Yusnarida Eka, Yessi Olivia, Umi Oktyari Retnaningsih, M. Saeri, Ahmad Jama’an, and Alfajri Alfajri. "THE PEATLAND RESTORATION AGENCY’S ECONOMIC REVITALIZATION PROGRAM IN ACHIEVING THE TRANSBOUNDARY HAZE-FREE ASEAN 2020 IN RIAU PROVINCE." Berumpun: International Journal of Social, Politics, and Humanities 4, no. 2 (October 30, 2021): 167–83. http://dx.doi.org/10.33019/berumpun.v4i2.61.

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This study analyses the implementation of good governance principles for the economic revitalization program under the supervision of Riau Province’s Badan Restorasi Gambut (Peatland Restoration Agency). One of the aims of this program is to support the haze-free ASEAN 2020 roadmap. Riau province is an area prone to forest fire disasters. Its peatland area, which is larger than Malaysia’s total peatlands, have a very high potential for damage due to forest fires. To mitigate the damages, BRG initiated the 3R program: Rewetting, Revegetation, and Revitalization. What makes this topic interesting is BRG emphasizes the aspects of economic empowerment of local communities to prevent further forest and peatland damages. To assess the implementation of BRG’s program, our research team conducted several interviews with representatives from Indonesia’s Ministry of Environment and Forestry, NGOs, academics, farmers, and villages’ facilitators who assisted local communities that received the BRG’s assistance packages. Our study shows that BRG’s economic revitalization program had succeeded in creating small scale economic activities such as honey industry, pineapple farming, and catfish farming. However, the ineffective coordination and communication between BRG and the local communities had prevented them from constructing an effective method to prevent future forest fires.

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Papadopoulos, Natalia, Johan Lennartsson, and Carl-Henrik Heldin. "PDGFRβ translocates to the nucleus and regulates chromatin remodeling via TATA element–modifying factor 1." Journal of Cell Biology 217, no. 5 (March 15, 2018): 1701–17. http://dx.doi.org/10.1083/jcb.201706118.

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Translocation of full-length or fragments of receptors to the nucleus has been reported for several tyrosine kinase receptors. In this paper, we show that a fraction of full-length cell surface platelet-derived growth factor (PDGF) receptor β (PDGFRβ) accumulates in the nucleus at the chromatin and the nuclear matrix after ligand stimulation. Nuclear translocation of PDGFRβ was dependent on PDGF-BB–induced receptor dimerization, clathrin-mediated endocytosis, β-importin, and intact Golgi, occurring in both normal and cancer cells. In the nucleus, PDGFRβ formed ligand-inducible complexes with the tyrosine kinase Fer and its substrate, TATA element–modifying factor 1 (TMF-1). PDGF-BB stimulation decreased TMF-1 binding to the transcriptional regulator Brahma-related gene 1 (Brg-1) and released Brg-1 from the SWI–SNF chromatin remodeling complex. Moreover, knockdown of TMF-1 by small interfering RNA decreased nuclear translocation of PDGFRβ and caused significant up-regulation of the Brg-1/p53-regulated cell cycle inhibitor CDKN1A (encoding p21) without affecting PDGFRβ-inducible immediate-early genes. In conclusion, nuclear interactions of PDGFRβ control proliferation by chromatin remodeling and regulation of p21 levels.

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Kullmann, Jan A., Sophie Meyer, Fabrizia Pipicelli, Christina Kyrousi, Felix Schneider, Nora Bartels, Silvia Cappello, and Marco B. Rust. "Profilin1-Dependent F-Actin Assembly Controls Division of Apical Radial Glia and Neocortex Development." Cerebral Cortex 30, no. 6 (December 20, 2019): 3467–82. http://dx.doi.org/10.1093/cercor/bhz321.

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Abstract Neocortex development depends on neural stem cell proliferation, cell differentiation, neurogenesis, and neuronal migration. Cytoskeletal regulation is critical for all these processes, but the underlying mechanisms are only poorly understood. We previously implicated the cytoskeletal regulator profilin1 in cerebellar granule neuron migration. Since we found profilin1 expressed throughout mouse neocortex development, we here tested the hypothesis that profilin1 is crucial for neocortex development. We found no evidence for impaired neuron migration or layering in the neocortex of profilin1 mutant mice. However, proliferative activity at basal positions was doubled in the mutant neocortex during mid-neurogenesis, with a drastic and specific increase in basal Pax6+ cells indicative for elevated numbers of basal radial glia (bRG). This was accompanied by transiently increased neurogenesis and associated with mild invaginations resembling rudimentary neocortex folds. Our data are in line with a model in which profilin1-dependent actin assembly controls division of apical radial glia (aRG) and thereby the fate of their progenies. Via this mechanism, profilin1 restricts cell delamination from the ventricular surface and, hence, bRG production and thereby controls neocortex development in mice. Our data support the radial cone hypothesis” claiming that elevated bRG number causes neocortex folds.

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Cho, Jae Yoong, Jong-Kwan Woo, Jialiang Yan, Rebecca L. Peterson, and Khalil Najafi. "Fused-Silica Micro Birdbath Resonator Gyroscope ($\mu$-BRG)." Journal of Microelectromechanical Systems 23, no. 1 (February 2014): 66–77. http://dx.doi.org/10.1109/jmems.2013.2291534.

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Otali, Emily, and Jason S. Gilchrist. "THE EFFECTS OF REFUSE FEEDING ON BODY CONDITION, REPRODUCTION, AND SURVIVAL OF BANDED MONGOOSES." Journal of Mammalogy 85, no. 3 (June 2004): 491–97. http://dx.doi.org/10.1644/brg-021.

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Burton, Cole, and Charles J. Krebs. "INFLUENCE OF RELATEDNESS ON SNOWSHOE HARE SPACING BEHAVIOR." Journal of Mammalogy 84, no. 3 (August 2003): 1100–1111. http://dx.doi.org/10.1644/brg-029.

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Liu, He, De-Hua Wang, and Zu-Wang Wang. "ENERGY REQUIREMENTS DURING REPRODUCTION IN FEMALE BRANDT'S VOLES (MICROTUS BRANDTII)." Journal of Mammalogy 84, no. 4 (November 2003): 1410–16. http://dx.doi.org/10.1644/brg-030.

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Clark, Jay E., Jennifer L. Parsons, Eric C. Hellgren, Eric E. Jorgensen, and David M. Leslie. "NITROGEN CONCENTRATION OF STOMACH CONTENTS AS AN INDEX OF DIETARY NITROGEN FOR SIGMODON HISPIDUS." Journal of Mammalogy 84, no. 4 (November 2003): 1399–409. http://dx.doi.org/10.1644/brg-105.

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Journal articles on the topic 'BRG'

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