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Purpose: In LOTUS (NCT02162719), adding the oral AKT inhibitor ipatasertib to first-line paclitaxel for locally advanced/metastatic triple-negative breast cancer (aTNBC) improved progression-free survival (PFS; primary endpoint), with an enhanced effect in patients with PIK3CA/AKT1/PTEN-altered tumors (FoundationOne next-generation sequencing [NGS] assay). We report final overall survival (OS) results. Methods: Eligible patients had measurable previously untreated aTNBC. Patients were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status, and were randomized 1:1 to paclitaxel 80 mg/m2 (days 1, 8, 15) plus ipatasertib 400 mg or placebo (days 1–21) every 28 days until disease progression or unacceptable toxicity. OS (intent-to-treat [ITT], immunohistochemistry PTEN-low, and PI3K/AKT pathway-activated [NGS PIK3CA/AKT1/PTEN-altered] populations) was a secondary endpoint. Results: Median follow-up was 19.0 versus 16.0 months in the ipatasertib–paclitaxel versus placebo–paclitaxel arms, respectively. In the ITT population (n = 124), median OS was numerically longer with ipatasertib–paclitaxel than placebo–paclitaxel (hazard ratio 0.80, 95% CI 0.50–1.28; median 25.8 vs 16.9 months, respectively; 1-year OS 83% vs 68%). Likewise, median OS favored ipatasertib–paclitaxel in the PTEN-low (n = 48; 23.1 vs 15.8 months; hazard ratio 0.83) and PIK3CA/AKT1/PTEN-altered (n = 42; 25.8 vs 22.1 months; hazard ratio 1.13) subgroups. The ipatasertib–paclitaxel safety profile was unchanged. Conclusions: Final OS results show a numerical trend favoring ipatasertib–paclitaxel and median OS exceeding 2 years with ipatasertib–paclitaxel. Overall, results are consistent with the reported PFS benefit; interpretation within biomarker-defined subgroups is complicated by small sample sizes and TNBC heterogeneity. [ABSTRACT FROM AUTHOR]

In this study, we propose a method for estimating the amount of expansion that occurs in subsea pipelines, which could be applied in the design of robust structures that transport oil and gas from offshore wells. We begin with a literature review and general discussion of existing estimation methods and terminologies with respect to subsea pipelines. Due to the effects of high pressure and high temperature, the production of fluid from offshore wells is typically caused by physical deformation of subsea structures, e.g., expansion and contraction during the transportation process. In severe cases, vertical and lateral buckling occurs, which causes a significant negative impact on structural safety, and which is related to on-bottom stability, free-span, structural collapse, and many other factors. In addition, these factors may affect the production rate with respect to flow assurance, wax, and hydration, to name a few. In this study, we developed a simple and efficient method for generating a reliable pipe expansion design in the early stage, which can lead to savings in both cost and computation time. As such, in this paper, we propose an applicable diagram, which we call the standard dimensionless ratio (SDR) versus virtual anchor length (LA) diagram, that utilizes an efficient procedure for estimating subsea pipeline expansion based on applied reliable scenarios. With this user guideline, offshore pipeline structural designers can reliably determine the amount of subsea pipeline expansion and the obtained results will also be useful for the installation, design, and maintenance of the subsea pipeline. [ABSTRACT FROM AUTHOR]

A 16-channel transceiver radiofrequency (RF) array using Helmholtz coils was designed to improve the RF transmission | B |-field homogeneity for human brain magnetic resonance imaging (MRI) at 7 T. A numerical simulation of the proposed Helmholtz transceiver array was performed using the finite-difference time-domain method-the subset of the finite-element method simulation. The simulation results of proposed 16-channel Helmholtz transceiver array were compared with the generally used rectangular transceiver array in term of their | B |-field and specific absorption rate (SAR). The simulation of each single element in 16-channel Helmholtz and rectangular transceiver arrays was compared using water phantom in term of their magnetic flux | B | homogeneity for the full width at half maximum. From the simulation results, the proposed 16-channel Helmholtz transceiver array configuration offers superior | B |-field homogeneity and low SAR at 7 T. These modifications to the coil geometries of the transceiver array coil could be applied to a 7-T MRI, and also extended to increase the homogenous coverage on | B |field with low SAR. [ABSTRACT FROM AUTHOR]

Tumor progression is a multiple step process in which, in addition to oncogenic mutation, other supporting factors can contribute to transformation. The role these factors have in cancer is an open question. Using the Eμ-myc model of B-cell transformation, we evaluated the contribution of the cytokine interleukin-7 (IL-7) in supporting lymphomagenesis. We have previously shown that disruption of the Y449xxM motif of the IL-7 receptor alpha (IL-7Rα) in a knock-in mouse model (IL-7Rα449F) has minor effects on lymphocyte production, but interferes with the activation of survival effectors. To address the hypothesis that targeted signal ablation would selectively affect lymphocyte transformation, IL-7Rα449F mice were crossed with two lymphomagenesis models, transgenic (Tg) IL-7 and Eμ-myc mice. We found that the loss of IL-7Rα Y449 signaling prevented Tg IL-7-mediated T- and B-lymphocyte transformation and decreased the development of Eμ-myc-induced B-cell tumors. We showed that the IL-7Rα449F mutation prevented increased survival of Tg IL-7 CD8 T cells, and decreased viability of bone marrow progenitor B cells, as well as Eμ-myc-induced proliferation. This study shows that IL-7Rα Y449 is important for lymphocyte transformation, and that unlike deficiencies in pre-B cell receptor signaling, Myc overexpression cannot compensate for the loss of IL-7Rα signals in early B-cell development. [ABSTRACT FROM AUTHOR]

PurposeTo compare retinal nerve fibre layer (RNFL) thickness changes between mitochondrial DNA (mtDNA) mutations at nucleotides 11778 and 14484 in Leber's hereditary optic neuropathy (LHON) using optical coherence tomography (OCT).MethodsThirty LHON patients with mtDNA mutations at nucleotides 11778 or 14484 underwent full ophthalmologic examinations including Stratus OCT. Patients were divided into four groups according to disease duration (early6 months, late>6 months) and mtDNA mutation type (11778 and 14484), and their RNFL thicknesses were compared.ResultsAverage RNFL thickness in the early 11778 group was significantly greater than that in the early 14484 group (P=0.04). Average RNFL thickness in the late 11778 group was significantly less than that in the late 14484 group (P=0.02). Quadrant analysis of the superior, nasal, and inferior quadrant RNFL thickness in the late 11778 group showed more severe RNFL atrophy than in the late 14484 group (P=0.023, 0.015, 0.003, respectively).ConclusionsRNFL thickness was significantly increased in the early stage and decreased in the late stage in the 11778 group than in the 14484 group. [ABSTRACT FROM AUTHOR]

Capecitabine, a prodrug of 5-FU, has been reported to generate maximal tumour activity at tumour sites and/or to improve drug tolerability as compared with 5-FU infusion, and it has also been demonstrated to act synergistically with irinotecan against some solid cancers. A previous study concluded that dose-intensified biweekly capecitabine seems to be more effective at increasing both response rate and progression-free survival time than conventional dose and schedule of capecitabine in colon cancer. We conducted this study to ascertain the efficacy and toxicity of dose-intensified biweekly capecitabine and irinotecan combination chemotherapy in chemotherapy-naïve advanced or metastatic gastric cancer patients. Patients were treated with irinotecan 130 mg m−2 intravenously for 90 min on days 1 and 15. Capecitabine at 3500 mg m−2 day−1, divided into two sessions per day, was administered for seven consecutive days from days 1 and 15, and followed by a 7-day drug-free period, respectively. Fifty-five eligible patients were enrolled in this study from November 2003 to April 2006. There were 22 women and 33 men: median patient age was 54 years (range: 27–81). A total of 200 treatment cycles were administered at a median number of four per patient (range: 1–9). Intent-to-treatment analysis showed that one patient achieved complete response (1.8%), 23 partial response (41.8%), 15 stable disease (27.3%), 10 progressive disease (18.2%) and 6 were non-evaluable (10.9%). The overall response rate was 43.6% (95% confidence interval: 30.2–56.9). The common grade 3–4 toxicities were neutropenia in 12 (21.8%), nausea/vomiting in 3 (5.4%) and diarrhea in 4 (7.2%) patients. Median time to progression was 5 months (range: 0.5–11 months), median survival duration was 11 months (range: 0.5–45 months) and median response duration was 6 months (range: 0.5–9 months). Biweekly dose-intensified capecitabine and irinotecan combination chemotherapy was active for the treatment of advanced or metastatic gastric cancers with a tolerable safety profile.British Journal of Cancer (2007) 96, 1514–1519. doi:10.1038/sj.bjc.6603752 www.bjcancer.com Published online 1 May 2007 [ABSTRACT FROM AUTHOR]

We conducted this study to ascertain the efficacy and toxicity of docetaxel and cisplatin combined with oral UFT and leucovorin as a first-line treatment for patients with advanced gastric cancer. In all, 52 patients received courses of docetaxel 60 mg m(-2) intravenously (i.v.) for 1 h and then cisplatin 75 mg m(-2) i.v. for 2 h on day 1. Oral UFT at 400-600 mg day(-1), as determined by body surface area, and leucovorin at 75 mg day(-1) were administered for 21 consecutive days from day 1, and this was followed by a 7-day drug-free interval. A total of 225 courses were administered, and the median number of courses per patient was four. Four complete responses (7.7%) and 22 partial responses (42.3%) were achieved, giving an overall response rate of 50% (95% Confidence Interval: 36.4-63.6%). The major toxicity was neutropenia, which reached grade 3/4 in 36 patients (69.3%). Grade 3/4 nausea and vomiting was observed in 12 patients (23.1%). Median time to progression was 22 weeks (4 to 156+ weeks), median survival duration was 48 weeks (4 to 156+ weeks), and median response duration was 24 weeks (6-152 weeks). We conclude that docetaxel, cisplatin, oral UFT, and leucovorin combination chemotherapy is effective and tolerable for the treatment of advanced gastric cancer. [ABSTRACT FROM AUTHOR]

A gratuitous strain was developed by disrupting the GAL1 gene (galactokinase) of recombinant Saccharomyces cerevisiae harboring the antithrombotic hirudin gene in the chromosome under the control of the GAL10 promoter. A series of glucose-limited fed-batch cultures were carried out to examine the effects of glucose supply on hirudin expression in the gratuitous strain. Controlled feeding of glucose successfully supported both cell growth and hirudin expression in the gratuitous strain. The optimum fed-batch culture done by feeding glucose at a rate of 0.3 g h-1 produced a maximum hirudin concentration of 62.1 mg l-1, which corresponded to a 4.5-fold increase when compared with a simple batch culture done with the same strain. [ABSTRACT FROM AUTHOR]

The cyclohexanone monooxygenase (CHMO) gene of Acinetobacter sp. NCIMB 9871 was simultaneously expressed with the genes encoding molecular chaperones and foldases in Escherichia coli. While the expression of the CHMO gene alone resulted in the formation of inclusion bodies, coexpression of the chaperone or foldase genes remarkably increased the production of soluble CHMO enzyme in recombinant E. coli. Furthermore, it was found that molecular chaperones were more beneficial than foldases for enhancing active CHMO enzyme production. The recombinant E. coli strain simultaneously expressing the genes for CHMO, GroEL/GroES and DnaK/DnaJ/GrpE showed a specific CHMO activity of 111 units g-1 cell protein, corresponding to a 38-fold enhancement in CHMO activity compared with the control E. coli strain expressing the CHMO gene alone. [ABSTRACT FROM AUTHOR]

A new hydrodynamic/acoustic splitting method isemployed to predict aeroacoustic tonal noise of self-sustained oscillatory flows over the open cavity at low Mach numbers. Acoustic field is computed using a sixth-order compact scheme and a fourth-order Runge–Kutta method, with acoustic sources obtained from the unsteady incompressible Navier–Stokes calculation. First, numerical accuracy of the present splitting method is assessed for the aeolian tone generated by Karman vortex shedding from a circular cylinder at ReD = 200 and M∞ = 0.3. A direct comparison was made with solutions of direct acoustic numerical simulation (DaNS) and Curle's acoustic analogy. The fundamental mode characteristics of the cavity flows at (i) Reδ* = 850 and M∞ = 0.077 and (ii) Reδ* = 1620 and M∞ = 0.147 are examined by the present method, verifying the solution with the experimentally measured sound pressure level (SPL) spectra. A dual tone characteristic observed in experiment (Henderson 2000) for case (i) is also confirmed computationally by the present method. [ABSTRACT FROM AUTHOR]

Zero trans-influx assays of glucose and xylose were performed using Saccharomyces cerevisiae to investigate transport characteristics under high and low glucose conditions. Under high glucose conditions, most glucose was transported by the low-affinity transporter. The high-affinity transporter was expressed under low glucose conditions, transporting over 50% glucose. Inhibition kinetics revealed that xylose was transported by both high- and low-affinity glucose transporters. Affinities of both glucose transporters for xylose were very low under high glucose condition but increased to a similar level to glucose under low glucose condition. The maximum rate of xylose transport increased by 85%, while an overall maximum glucose transport rate decreased by 42% under low glucose condition, indicating the presence of other transport system for sugars except for glucose. It was suggested that expression of the high-affinity transporter and increased affinity of glucose transporters for xylose under low glucose condition would provide a fermentation strategy for enhancing the productivity of xylitol by recombinant S. cerevisiae harboring the xylose reductase gene. [ABSTRACT FROM AUTHOR]

In this study, we summarize our long-term follow-up data of 24 patients who underwent autologous peripheral blood stem cell transplantation (PBSCT) using the dump-freezing method in a -80 degrees C freezer. Collected peripheral blood mononuclear cells were mixed with a cryoprotectant solution consisting of autologous plasma and 20% dimethyl sulfoxide, then placed in a -80 degrees C freezer. The recovery rate of mononuclear cells (MNCs), colony-forming unit-granulocyte/macrophage (CFU-GM) colonies, and CD34+ cells were calculated. Engraftment time (with neutrophil count > 0.5 x 10(9)/L, platelet count > 50 x 10(9)/L) and normal hemopoiesis (neutrophil count > 2 x 10(9)/L, platelet count > 100 x 10(9)/L) were evaluated. Median duration of cryopreservation was 76 days. The mean recovery rates of MNCs, CFU-GM colonies, and CD34+ cells were 93.4%, 78.4%, and 95.3%, respectively. The median engraftment times of neutrophils and platelets were 8 and 27 days, respectively. The median normal hemopoiesis times of neutrophil and platelet were 31 and 45 days, respectively. Nine patients are alive and in complete remission (CR). Seven patients in first CR sustained normal hemopoiesis with a median duration of 35 months. Two patients, who achieved second CR after salvage chemotherapy due to a leukemia relapse after PBSCT, maintained engraftment status for 24 and 28 months, and 1 reached normal hemopoiesis. These results demonstrate that PBSCT using the dump-freezing method in a -80 degrees C freezer leads to acceptable long-term engraftment stability. [ABSTRACT FROM AUTHOR]

Objective: To assess the changing status of women after hysterectomy using the electrodiagnostic method.Study Design: We compared pre- and postoperative somatosensory evoked potentials (SSEPs) through vaginal stimulation in twenty patients undergoing hysterectomy.Results: 1) The latencies (Mean +/- SD) of the first positive peak (P1) and first negative peak (N1) in preoperative vaginal SSEP were 32.89 +/- 3.02 ms and 40.41 +/- 3.43 ms in the left side, 33.25 +/- 4.28 ms and 41.39 +/- 5.46 ms in the right side respectively. 2) The postoperative P1 and N1 latencies were 33.68 +/- 4.50 ms and 42.00 +/- 4.30 ms in the left side, 33.78 +/- 3.10 ms and 42.00 +/- 3.62 in the right side respectively.Conclusion: There were no significant differences between the pre- and the postoperative vaginal SSEP by stimulating vagina in patients of hysterectomy. [ABSTRACT FROM AUTHOR]

The use of circulating fluidized bed combustion in coal power plants is dramatically increasing, and the disposal of the resultant ash is a significant environmental concern. The present study investigated the binder chemistry of sodium carbonate-activated CFBC fly ash. Compressive strength tests showed that strength development was relatively faster in samples with 5% sodium carbonate. The main binder gel in samples with and without sodium carbonate was composed of AFt, AFm and C-S-H, while the formation and Al-substitution in C-S-H was enhanced by sodium carbonate-activation. At an excessive dosage of sodium carbonate, the formation of AFt was significantly hindered due to the precipitation of sodium sulfate, and a notable amount of AFm was formed in its place. The results obtained in this study fill a deficit in the understanding of fly ash activated with near-neutral salts, which are used extensively in several industrial applications, including alkali-activated cements. [ABSTRACT FROM AUTHOR]