Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Cryo-EM structure of the DNA-PK holoenzyme

doi: 10.1073/pnas.1707386114

Figure Lengend Snippet: The overall DNA-PKcs structure. (A) SDS/PAGE of two fractions of the DNA-PK sample eluted from the last Superose 6 step of the purification. The right lane was used for cryo-EM data collection. (B) A cryo-EM micrograph of DNA-PK (Upper) and five 2D classes of DNA-PK (Bottom). (C) Angular distribution for the initial DNA-PK data set (∼860K particles) (Left) and filtered data set (∼290K particles) that removed two-thirds of particles at the preferred orientation (Right). Each cylinder represents one view, and the height is scaled to the number of particles in that view. (D) The FSC curve of the final refined cryo-EM map of DNA-PKcs at an estimated resolution of 4.4 Å.

Article Snippet: If the Ku80 CTR globular domain exists in the class 6 map, it would have been in clash with the arm (purple). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. S4. caption a7 DNA-PK cryo-EM structure reveals Ku80 CTR binding site. ( A ) Six classes of DNA-PKcs: class 1 (yellow), class 2 (blue), class 3 (pink), class 4 (salmon), class 5 (green), and class 6 (wheat).

Techniques: SDS Page, Purification, Cryo-EM Sample Prep

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Cryo-EM structure of the DNA-PK holoenzyme

doi: 10.1073/pnas.1707386114

Figure Lengend Snippet: The overall DNA-PKcs structure. (A) Schematics of DNA-PKcs domain architecture showing the three units of the DNA-PKcs structure: N-terminal region with arm (red) and bridge (magenta), the circular cradle (blue) and the head domain containing FAT (FRAP-ATM-TRRAP) (green), FRB (FKBP12-rapamycin-binding) (orange), kinase (yellow), and FATC (FAT C-terminal) (dark green) domains. (B) Cryo-EM density of DNA-PKcs at 4.4-Å resolution. (C) Overall resolution distribution of DNA-PKcs cryo-EM map. Two different views are shown on the Left and Right. (Middle) Cut-through section of DNA-PKcs. The resolution range is color-coded. (D) Cartoon representation of DNA-PKcs model in orientations similar to in B.

Article Snippet: If the Ku80 CTR globular domain exists in the class 6 map, it would have been in clash with the arm (purple). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. S4. caption a7 DNA-PK cryo-EM structure reveals Ku80 CTR binding site. ( A ) Six classes of DNA-PKcs: class 1 (yellow), class 2 (blue), class 3 (pink), class 4 (salmon), class 5 (green), and class 6 (wheat).

Techniques: Binding Assay, Cryo-EM Sample Prep

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Cryo-EM structure of the DNA-PK holoenzyme

doi: 10.1073/pnas.1707386114

Figure Lengend Snippet: Segments of DNA-PKcs represented in sticks fitted in the 4.4-Å-resolution cryo-EM map.

Article Snippet: If the Ku80 CTR globular domain exists in the class 6 map, it would have been in clash with the arm (purple). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. S4. caption a7 DNA-PK cryo-EM structure reveals Ku80 CTR binding site. ( A ) Six classes of DNA-PKcs: class 1 (yellow), class 2 (blue), class 3 (pink), class 4 (salmon), class 5 (green), and class 6 (wheat).

Techniques: Cryo-EM Sample Prep

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Cryo-EM structure of the DNA-PK holoenzyme

doi: 10.1073/pnas.1707386114

Figure Lengend Snippet: (A) DNA-PKcs model fitted in the cryo-EM density map (B) Superposition of DNA-PKcs models from cryo-EM (red) and from the crystal structure (PDB: 5LUQ) (blue). The segment that was absent in the cryo-EM map but was built as unassigned sequences in the crystal structure is indicated.

Article Snippet: If the Ku80 CTR globular domain exists in the class 6 map, it would have been in clash with the arm (purple). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. S4. caption a7 DNA-PK cryo-EM structure reveals Ku80 CTR binding site. ( A ) Six classes of DNA-PKcs: class 1 (yellow), class 2 (blue), class 3 (pink), class 4 (salmon), class 5 (green), and class 6 (wheat).

Techniques: Cryo-EM Sample Prep

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Cryo-EM structure of the DNA-PK holoenzyme

doi: 10.1073/pnas.1707386114

Figure Lengend Snippet: Conformational dynamics of the DNA-PKcs arm. Variations in the arm conformation in six classes of cryo-EM data are shown as cartoons: class 1 (cyan), class 2 (teal), class 3 (wheat), class 4 (light green), class 5 (light magenta), and class 6 (pink).

Article Snippet: If the Ku80 CTR globular domain exists in the class 6 map, it would have been in clash with the arm (purple). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. S4. caption a7 DNA-PK cryo-EM structure reveals Ku80 CTR binding site. ( A ) Six classes of DNA-PKcs: class 1 (yellow), class 2 (blue), class 3 (pink), class 4 (salmon), class 5 (green), and class 6 (wheat).

Techniques: Cryo-EM Sample Prep

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Cryo-EM structure of the DNA-PK holoenzyme

doi: 10.1073/pnas.1707386114

Figure Lengend Snippet: DNA-PK cryo-EM structure reveals Ku80 CTR binding site. (A) Six classes of DNA-PKcs: class 1 (yellow), class 2 (blue), class 3 (pink), class 4 (salmon), class 5 (green), and class 6 (wheat). Extra density of Ku80 CTR is shown in cyan. The percentage of the total number of particles included is indicated at the bottom of each of the classes. (B) The FSC curve of refined class2 cryo-EM map at an estimated resolution of 5.8 Å. (C) Ku80 CTR globular domain NMR structure (PDB: 1Q2Z) fitted in the segmented extra density of class 2.

Article Snippet: If the Ku80 CTR globular domain exists in the class 6 map, it would have been in clash with the arm (purple). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. S4. caption a7 DNA-PK cryo-EM structure reveals Ku80 CTR binding site. ( A ) Six classes of DNA-PKcs: class 1 (yellow), class 2 (blue), class 3 (pink), class 4 (salmon), class 5 (green), and class 6 (wheat).

Techniques: Cryo-EM Sample Prep, Binding Assay

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Cryo-EM structure of the DNA-PK holoenzyme

doi: 10.1073/pnas.1707386114

Figure Lengend Snippet: DNA-PK cryo-EM structure reveals Ku80 CTR binding site. (A) Schematics of Ku70 and Ku80 domains. (B) Cryo-EM density of refined DNA-PK in class 2 at 5.8-Å resolution. (Left) Two panels showing the proposed Ku80 CTR density (cyan). (Right) Two panels showing the resolution distribution of DNA-PK with color-coded resolution range. (C) DNA-PK structure with highlighted structural features: arm (red), Ku80 CTR globular domain (cyan), and modeled Ku80 CTR linker and last helix fragments from the crystal structure [Protein Data Bank (PDB): 5LUQ] (teal). (D) Ku80 CTR globular domain (cyan) may have moved the arm (red) upward in the class 2 map. If the Ku80 CTR globular domain exists in the class 6 map, it would have been in clash with the arm (purple).

Article Snippet: If the Ku80 CTR globular domain exists in the class 6 map, it would have been in clash with the arm (purple). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. S4. caption a7 DNA-PK cryo-EM structure reveals Ku80 CTR binding site. ( A ) Six classes of DNA-PKcs: class 1 (yellow), class 2 (blue), class 3 (pink), class 4 (salmon), class 5 (green), and class 6 (wheat).

Techniques: Cryo-EM Sample Prep, Binding Assay

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Cryo-EM structure of the DNA-PK holoenzyme

doi: 10.1073/pnas.1707386114

Figure Lengend Snippet: A structural model for the DNA-PK interaction with DNA. (A) Two views of a previously reported DNA-PK map at 25-Å resolution (EMD-1209, gray), fitted with our DNA-PK structure (gray) that contains DNA-PKcs and Ku80 CTR, and with the Ku70/80 core crystal structure (PDB: 1JEY, pink and slate). The fitted orientation of the Ku70/80 core is only approximate and was achieved by placing the Ku80 core close to the Ku80 CTR. The circle highlights the Ku70/80 core domains that mediate DNA binding. The proposed movement of the core domains resulting from the flexible linker between the Ku80 core and the CTR is shown as dashed black curvy lines. (B) 30-bp DNA duplex (black) modeled in the DNA-PK structure. (Left) DNA distal end at the front aperture. (Right) DNA free end at the bottom aperture.

Article Snippet: If the Ku80 CTR globular domain exists in the class 6 map, it would have been in clash with the arm (purple). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. S4. caption a7 DNA-PK cryo-EM structure reveals Ku80 CTR binding site. ( A ) Six classes of DNA-PKcs: class 1 (yellow), class 2 (blue), class 3 (pink), class 4 (salmon), class 5 (green), and class 6 (wheat).

Techniques: Binding Assay

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Cryo-EM structure of the DNA-PK holoenzyme

doi: 10.1073/pnas.1707386114

Figure Lengend Snippet: A structural model for the interaction of DNA-PK with DNA. (A) Two views of DNA-PK map at 25-Å resolution (EMD-1209, gray) fitted with the DNA-PK structure, Ku70/80 crystal structure (PDB: 1JEY, pink and slate) and modeled with Ku80 C-terminal linker and helices from PDB: 5LUQ and a 30-bp duplex DNA. (B) DNA-PK cryo-EM structure dimer modeled with DNA duplex (black), Ku70/80 (PDB: 1JEY, pink and slate) in cryo-EM density of DNA-PK (EMD-1209, gray). The dimer orientation is derived from EMD-1210.

Article Snippet: If the Ku80 CTR globular domain exists in the class 6 map, it would have been in clash with the arm (purple). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. S4. caption a7 DNA-PK cryo-EM structure reveals Ku80 CTR binding site. ( A ) Six classes of DNA-PKcs: class 1 (yellow), class 2 (blue), class 3 (pink), class 4 (salmon), class 5 (green), and class 6 (wheat).

Techniques: Cryo-EM Sample Prep, Derivative Assay

Journal:

Article Title: In Vitro Activity of TD-6424 against Staphylococcus aureus

doi: 10.1128/AAC.47.11.3602-3604.2003

Figure Lengend Snippet: In vitro activities of TD-6424 and comparator antibiotics against MRSA and MSSA

Article Snippet: Linezolid at 8 μg/ml reduced the initial inoculum from log 10 5.76 ± 0.07 CFU/ml to log 10 2.73 ± 0.08 CFU/ml by 4 h, and vancomycin at 32 μg/ml decreased it from log 10 5.76 ± 0.07 CFU/ml to log 10 4.82 ± 0.02 CFU/ml over this period. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 1. caption a7 Time-kill curves for MSSA (ATCC 13709) (A), MRSA (ATCC 33591) (B), and GISA (HIP 5836) (C). (A) Vancomycin at 4 times the MIC (⧫), nafcillin at 4 times the MIC (▪), linezolid at 4 times the MIC (▴), and TD-6424 at 4 times the MIC (▵); (B) vancomycin at 8 times the MIC (⧫), linezolid at 8 times the MIC (▴), and TD-6424 at 8 (▵) and 32 (▪) times the MIC; (C) linezolid at 4 times the MIC (▴), vancomycin at 4 times the MIC (⧫), and TD-6424 at 4 (▵), 8 (▪), and 16 (□) times the MIC.

Techniques: In Vitro

Journal:

Article Title: In Vitro Activity of TD-6424 against Staphylococcus aureus

doi: 10.1128/AAC.47.11.3602-3604.2003

Figure Lengend Snippet: Time-kill curves for MSSA (ATCC 13709) (A), MRSA (ATCC 33591) (B), and GISA (HIP 5836) (C). (A) Vancomycin at 4 times the MIC (⧫), nafcillin at 4 times the MIC (▪), linezolid at 4 times the MIC (▴), and TD-6424 at 4 times the MIC (▵); (B) vancomycin at 8 times the MIC (⧫), linezolid at 8 times the MIC (▴), and TD-6424 at 8 (▵) and 32 (▪) times the MIC; (C) linezolid at 4 times the MIC (▴), vancomycin at 4 times the MIC (⧫), and TD-6424 at 4 (▵), 8 (▪), and 16 (□) times the MIC. ✻, bacterial growth control. The nafcillin MIC was 1 μg/ml for ATCC 13709. Vancomycin MICs were 1, 1, and 8 μg/ml for ATCC 13709, ATCC 33591, and HIP 5836, respectively; the corresponding values were 2, 2, and 2 μg/ml for linezolid and 1, 1, and 2 μg/ml for TD-6424.

Article Snippet: Linezolid at 8 μg/ml reduced the initial inoculum from log 10 5.76 ± 0.07 CFU/ml to log 10 2.73 ± 0.08 CFU/ml by 4 h, and vancomycin at 32 μg/ml decreased it from log 10 5.76 ± 0.07 CFU/ml to log 10 4.82 ± 0.02 CFU/ml over this period. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 1. caption a7 Time-kill curves for MSSA (ATCC 13709) (A), MRSA (ATCC 33591) (B), and GISA (HIP 5836) (C). (A) Vancomycin at 4 times the MIC (⧫), nafcillin at 4 times the MIC (▪), linezolid at 4 times the MIC (▴), and TD-6424 at 4 times the MIC (▵); (B) vancomycin at 8 times the MIC (⧫), linezolid at 8 times the MIC (▴), and TD-6424 at 8 (▵) and 32 (▪) times the MIC; (C) linezolid at 4 times the MIC (▴), vancomycin at 4 times the MIC (⧫), and TD-6424 at 4 (▵), 8 (▪), and 16 (□) times the MIC.

Techniques: Control

Journal:

Article Title: In Vitro Activity of TD-6424 against Staphylococcus aureus

doi: 10.1128/AAC.47.11.3602-3604.2003

Figure Lengend Snippet: PAE for TD-6424 and comparator antibiotics

Article Snippet: Linezolid at 8 μg/ml reduced the initial inoculum from log 10 5.76 ± 0.07 CFU/ml to log 10 2.73 ± 0.08 CFU/ml by 4 h, and vancomycin at 32 μg/ml decreased it from log 10 5.76 ± 0.07 CFU/ml to log 10 4.82 ± 0.02 CFU/ml over this period. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 1. caption a7 Time-kill curves for MSSA (ATCC 13709) (A), MRSA (ATCC 33591) (B), and GISA (HIP 5836) (C). (A) Vancomycin at 4 times the MIC (⧫), nafcillin at 4 times the MIC (▪), linezolid at 4 times the MIC (▴), and TD-6424 at 4 times the MIC (▵); (B) vancomycin at 8 times the MIC (⧫), linezolid at 8 times the MIC (▴), and TD-6424 at 8 (▵) and 32 (▪) times the MIC; (C) linezolid at 4 times the MIC (▴), vancomycin at 4 times the MIC (⧫), and TD-6424 at 4 (▵), 8 (▪), and 16 (□) times the MIC.

Techniques:

Journal: Antiviral therapy

Article Title: A 72-week randomized study of the safety and efficacy of a d4T to AZT switch at 24 weeks compared to AZT or TDF when given with 3TC and NVP

doi: 10.3851/IMP2497

Figure Lengend Snippet: GPO-VIR S30® is a fixed-dose combination that contains stavudine (d4T) 30 mg, lamivudine (3TC) 150 mg, and nevirapine (NVP) 200 mg. GPO-VIR Z250® is a fixeddose combination that contains zidovudine (AZT) 250 mg, 3TC 150 mg and NVP 200 mg. Truvada® is a fixed-dose combination that contains tenofovir disoproxil fumarate (TDF) 300 mg and emtricitabine (FTC) 200 mg. Arm 1 received GPO-VIR S30® twice daily for 24 weeks followed by GPO-VIR Z250® twice daily for 48 weeks. Arm 2 received GPO-VIR Z250® twice daily for 72 weeks, and arm 3 received Truvada® once daily and NVP 200 mg twice daily for 72 weeks. AE, adverse event; ARV, antiretroviral; LPV/r, lopinavir/ritonavir; LTFU, lost to follow-up; NNRTI, non-nucleoside reverse transcriptase inhibitor.

Article Snippet: Clinical characteristics were comparable among treatment groups with the baseline mean (SD) CD4 count of 161 (94) cells/mm 3 , log 10 plasma HIV RNA of 4.87 (0.65) copies/mL, the Hb of 12.5 (1.6) g/dL, and an eGFR of 83.0 (15.5) mL/min/1.73m 2 . table ft1 table-wrap mode="anchored" t5 caption a7 Parameter Arm 1 GPO-VIR S/GPO-VIR Z (n = 51) Arm 2 GPO-VIR Z (n = 49) Arm 3 Truvada/NVP (n = 48) All arms(n = 148) Site, n (%) Bangkok 29 (57) 29 (59) 29 (60) 87 (59) Chonburi 22 (43) 20 (41) 19 (40) 61 (41) CDC classification, n (%) A 25(49) 26 (53) 27 (56) 78 (53) B 23 (45) 21 (43) 21 (44) 65 (44) C 3 (6) 2 (4) 5 (3) Female, n (%) 28 (55) 28 (57) 25 (52) 81 (55) Mean (SD) age, years 35 (7) 34 (8) 35 (9) 34 (8) Mean (SD) weight, kg 56.7 (12.0) 58.2 (11.2) 58.9 (9.6) 57.9 (10.9) Mean (SD) CD4 count, cells/mm 3 154 (91) 174 (97) 157 (94) 161 (94) Mean (SD) plasma HIV RNA, log 10 copies/mL 4.8 (0.67) 4.9 (0.63) 4.9 (0.68) 4.9 (0.65) Mean (SD)hemoglogin (g/dL) 12.4 (1.7) 12.4 (1.6) 12.8 (1.6) 12.5 (1.6) Hemoglobin <10g/dL, n(%) 3 (6) 3 (6) 2 (4) 8 (5) Mean (SD) peripheral fat by DEXA scan, g 7380 (3792) 7460 (3229) 7850 (2586) 7559 (3237) Mean (SD) eGFR by MDRD, mL/min/1.73m 2 82.5 (12.8) 83.3 (15.5) 83.0 (18.3) 83.0 (15.5) Mean (SD) fasting lipids and glucose a Total cholesterol, mg/dL 164.3 (33.1) 168.2 (34.5) 177.8 (34.8) 170.0 (34.4) HDL cholesterol, mg/dL 38.9 (11.0) 40.5 (12.6) 41.4 (10.3) 40.2 (11.3) LDL cholesterol, mg/dL 96.1 (24.8) 98.2 (26.7) 107.3 (25.6) 100.4 (26.0) Triglycerides, mg/dL 112.9 (80.4) 111.4 (55.7) 108.0 (37.4) 110.8 (60.5) Glucose, mg/dL 82.1 (8.0) 82.7 (11.6) 83.5 (8.6) 82.8 (9.4) Open in a separate window a Included one patient in arm 3 who did not fast.

Techniques:

Journal: Antiviral therapy

Article Title: A 72-week randomized study of the safety and efficacy of a d4T to AZT switch at 24 weeks compared to AZT or TDF when given with 3TC and NVP

doi: 10.3851/IMP2497

Figure Lengend Snippet: Baseline characteristics of SEARCH 003 participants, by study arm

Article Snippet: Clinical characteristics were comparable among treatment groups with the baseline mean (SD) CD4 count of 161 (94) cells/mm 3 , log 10 plasma HIV RNA of 4.87 (0.65) copies/mL, the Hb of 12.5 (1.6) g/dL, and an eGFR of 83.0 (15.5) mL/min/1.73m 2 . table ft1 table-wrap mode="anchored" t5 caption a7 Parameter Arm 1 GPO-VIR S/GPO-VIR Z (n = 51) Arm 2 GPO-VIR Z (n = 49) Arm 3 Truvada/NVP (n = 48) All arms(n = 148) Site, n (%) Bangkok 29 (57) 29 (59) 29 (60) 87 (59) Chonburi 22 (43) 20 (41) 19 (40) 61 (41) CDC classification, n (%) A 25(49) 26 (53) 27 (56) 78 (53) B 23 (45) 21 (43) 21 (44) 65 (44) C 3 (6) 2 (4) 5 (3) Female, n (%) 28 (55) 28 (57) 25 (52) 81 (55) Mean (SD) age, years 35 (7) 34 (8) 35 (9) 34 (8) Mean (SD) weight, kg 56.7 (12.0) 58.2 (11.2) 58.9 (9.6) 57.9 (10.9) Mean (SD) CD4 count, cells/mm 3 154 (91) 174 (97) 157 (94) 161 (94) Mean (SD) plasma HIV RNA, log 10 copies/mL 4.8 (0.67) 4.9 (0.63) 4.9 (0.68) 4.9 (0.65) Mean (SD)hemoglogin (g/dL) 12.4 (1.7) 12.4 (1.6) 12.8 (1.6) 12.5 (1.6) Hemoglobin <10g/dL, n(%) 3 (6) 3 (6) 2 (4) 8 (5) Mean (SD) peripheral fat by DEXA scan, g 7380 (3792) 7460 (3229) 7850 (2586) 7559 (3237) Mean (SD) eGFR by MDRD, mL/min/1.73m 2 82.5 (12.8) 83.3 (15.5) 83.0 (18.3) 83.0 (15.5) Mean (SD) fasting lipids and glucose a Total cholesterol, mg/dL 164.3 (33.1) 168.2 (34.5) 177.8 (34.8) 170.0 (34.4) HDL cholesterol, mg/dL 38.9 (11.0) 40.5 (12.6) 41.4 (10.3) 40.2 (11.3) LDL cholesterol, mg/dL 96.1 (24.8) 98.2 (26.7) 107.3 (25.6) 100.4 (26.0) Triglycerides, mg/dL 112.9 (80.4) 111.4 (55.7) 108.0 (37.4) 110.8 (60.5) Glucose, mg/dL 82.1 (8.0) 82.7 (11.6) 83.5 (8.6) 82.8 (9.4) Open in a separate window a Included one patient in arm 3 who did not fast.

Techniques:

Journal: Antiviral therapy

Article Title: A 72-week randomized study of the safety and efficacy of a d4T to AZT switch at 24 weeks compared to AZT or TDF when given with 3TC and NVP

doi: 10.3851/IMP2497

Figure Lengend Snippet: Changes in hemoglobin, peripheral fat, neuropathic signs, peripheral neuropathy, renal function, CD4 count, and plasma HIV RNA, from baseline to week 24 and week 72, by study arm (intention to treat analysis)

Article Snippet: Clinical characteristics were comparable among treatment groups with the baseline mean (SD) CD4 count of 161 (94) cells/mm 3 , log 10 plasma HIV RNA of 4.87 (0.65) copies/mL, the Hb of 12.5 (1.6) g/dL, and an eGFR of 83.0 (15.5) mL/min/1.73m 2 . table ft1 table-wrap mode="anchored" t5 caption a7 Parameter Arm 1 GPO-VIR S/GPO-VIR Z (n = 51) Arm 2 GPO-VIR Z (n = 49) Arm 3 Truvada/NVP (n = 48) All arms(n = 148) Site, n (%) Bangkok 29 (57) 29 (59) 29 (60) 87 (59) Chonburi 22 (43) 20 (41) 19 (40) 61 (41) CDC classification, n (%) A 25(49) 26 (53) 27 (56) 78 (53) B 23 (45) 21 (43) 21 (44) 65 (44) C 3 (6) 2 (4) 5 (3) Female, n (%) 28 (55) 28 (57) 25 (52) 81 (55) Mean (SD) age, years 35 (7) 34 (8) 35 (9) 34 (8) Mean (SD) weight, kg 56.7 (12.0) 58.2 (11.2) 58.9 (9.6) 57.9 (10.9) Mean (SD) CD4 count, cells/mm 3 154 (91) 174 (97) 157 (94) 161 (94) Mean (SD) plasma HIV RNA, log 10 copies/mL 4.8 (0.67) 4.9 (0.63) 4.9 (0.68) 4.9 (0.65) Mean (SD)hemoglogin (g/dL) 12.4 (1.7) 12.4 (1.6) 12.8 (1.6) 12.5 (1.6) Hemoglobin <10g/dL, n(%) 3 (6) 3 (6) 2 (4) 8 (5) Mean (SD) peripheral fat by DEXA scan, g 7380 (3792) 7460 (3229) 7850 (2586) 7559 (3237) Mean (SD) eGFR by MDRD, mL/min/1.73m 2 82.5 (12.8) 83.3 (15.5) 83.0 (18.3) 83.0 (15.5) Mean (SD) fasting lipids and glucose a Total cholesterol, mg/dL 164.3 (33.1) 168.2 (34.5) 177.8 (34.8) 170.0 (34.4) HDL cholesterol, mg/dL 38.9 (11.0) 40.5 (12.6) 41.4 (10.3) 40.2 (11.3) LDL cholesterol, mg/dL 96.1 (24.8) 98.2 (26.7) 107.3 (25.6) 100.4 (26.0) Triglycerides, mg/dL 112.9 (80.4) 111.4 (55.7) 108.0 (37.4) 110.8 (60.5) Glucose, mg/dL 82.1 (8.0) 82.7 (11.6) 83.5 (8.6) 82.8 (9.4) Open in a separate window a Included one patient in arm 3 who did not fast.

Techniques:

Journal: Hepatology international

Article Title: Glecaprevir/pibrentasvir expands reach while reducing cost and duration of hepatitis C virus therapy

doi: 10.1007/s12072-018-9873-y

Figure Lengend Snippet: US FDA-approved HCV regimens in the United States

Article Snippet: GLE/PIB also has a favorable drug interaction profile and can be administered with amiodarone, unlike other FDC DAAs. table ft1 table-wrap mode="anchored" t5 caption a7 Harvoni Viekira Pak Zepatier Epclusa Mavyret Contains LDV/SOF PrOD ELB/GRZ SOF/VEL GLE/PIB Approved October 2014 January 2015 January 2016 June 2016 August 2017 Duration 8–24 weeks 12–24 weeks 12–16 weeks 12–24 weeks 8–16 weeks Cost (12 weeks) $94,500 $83,319 ± RBV $5000 $54,000 ± RBV $6700 $74,760 $39,600 Open in a separate window Prices based on listed wholesale acquisition costs LDV ledipasvir, SOF sofosbuvir, PrOD paritaprevir, ritonavir, ombitasvir, and dasabuvir, EBR elbasvir, GRZ grazoprevir, VEL velptasvir, GLE glecaprevir, PIB pibrentasvir, RBV ribavirin US FDA-approved HCV regimens in the United States

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of Aerosolized Colistin in a Mouse Lung Infection Model

doi: 10.1128/AAC.01965-17

Figure Lengend Snippet: Visual predictive checks for bacterial growth in the lungs for P. aeruginosa ATCC 27853 (A), PAO1 (B), and FADDI-PA022 (C). P50, median model-predicted bacterial load; P10, model-predicted 10th percentile bacterial load; P90, model-predicted 90th percentile bacterial load.

Article Snippet: Broken lines, the initial inoculum at the start of the experiment. table ft1 table-wrap mode="anchored" t5 TABLE 3 caption a7 Kill level f AUC/MIC ATCC 27853 PAO1 FADDI-PA022 Observed value Simulated value Observed value Simulated value Observed value Simulated value Stasis 2.99 (2.47–4.17) 3.62 (2.00–4.10) 3.29 (2.90–3.91) 3.48 (1.52–10.4) 2.15 (1.90–2.45) 2.85 (0.80–4.12) 1-log 10 kill ND ND 4.68 (3.48–5.23) 5.55 (1.99–14.82) 2.60 (2.25–3.50) 4.36 (0.88–4.55) Open in a separate window a Data for observed values are from reference 14 .

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of Aerosolized Colistin in a Mouse Lung Infection Model

doi: 10.1128/AAC.01965-17

Figure Lengend Snippet: Log10 CFU per lung of P. aeruginosa ATCC 27853 (A), PAO1 (B), and FADDI-PA022 (C) at 24 h versus the colistin exposure in plasma (fAUC/MIC) in neutropenic infected mice. The observed bacterial load in neutropenic infected mice (14) and the simulated bacterial load obtained using the developed MBM are shown. Broken lines, the initial inoculum at the start of the experiment.

Article Snippet: Broken lines, the initial inoculum at the start of the experiment. table ft1 table-wrap mode="anchored" t5 TABLE 3 caption a7 Kill level f AUC/MIC ATCC 27853 PAO1 FADDI-PA022 Observed value Simulated value Observed value Simulated value Observed value Simulated value Stasis 2.99 (2.47–4.17) 3.62 (2.00–4.10) 3.29 (2.90–3.91) 3.48 (1.52–10.4) 2.15 (1.90–2.45) 2.85 (0.80–4.12) 1-log 10 kill ND ND 4.68 (3.48–5.23) 5.55 (1.99–14.82) 2.60 (2.25–3.50) 4.36 (0.88–4.55) Open in a separate window a Data for observed values are from reference 14 .

Techniques: Clinical Proteomics, Infection

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of Aerosolized Colistin in a Mouse Lung Infection Model

doi: 10.1128/AAC.01965-17

Figure Lengend Snippet: (A) Deterministic simulation of population average ELF concentration-versus-time profile of formed colistin following pulmonary nebulization (I.T.) of CMS at 30 and 60 mg CBA twice daily in critically ill patients. Deterministic simulation of bacterial growth in the lungs following exposure to aerosolized CMS at 30 and 60 mg CBA twice daily in critically ill patients for P. aeruginosa ATCC 27853 (B), PAO1 (C), and FADDI-PA022 (D).

Article Snippet: Broken lines, the initial inoculum at the start of the experiment. table ft1 table-wrap mode="anchored" t5 TABLE 3 caption a7 Kill level f AUC/MIC ATCC 27853 PAO1 FADDI-PA022 Observed value Simulated value Observed value Simulated value Observed value Simulated value Stasis 2.99 (2.47–4.17) 3.62 (2.00–4.10) 3.29 (2.90–3.91) 3.48 (1.52–10.4) 2.15 (1.90–2.45) 2.85 (0.80–4.12) 1-log 10 kill ND ND 4.68 (3.48–5.23) 5.55 (1.99–14.82) 2.60 (2.25–3.50) 4.36 (0.88–4.55) Open in a separate window a Data for observed values are from reference 14 .

Techniques: Concentration Assay

Journal: AIDS care

Article Title: Menstrual cycle phase and single tablet antiretroviral medication adherence in women with HIV

doi: 10.1080/09540121.2015.1069787

Figure Lengend Snippet: Multi-class single tablet regimens included in the study.

Article Snippet: Photographic medication cards were used to aide in identifying each drug used by the participant. table ft1 table-wrap mode="anchored" t5 caption a7 Brand Name Active Ingredients Dosing Atripla Efavirenz, Emtricitabine, Tenofovir Once a day Complera Emtricitabine, Rilpivirine, Tenofovir Once a day Stribild Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Once a day Trizivir Abacavir, Lamivudine, Zidovudine Twice daily Open in a separate window Multi-class single tablet regimens included in the study.

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