This paper presents a new control strategy for the rotor-side converter (RSC) of wind turbines (WTs) based on doubly fed induction generators (DFIG) that intends to improve its low-voltage ride ...through capability. The main objective of this work is to design an algorithm that would enable the system to control the initial overcurrents that appear in the generator during voltage sags, which can damage the RSC, without tripping it. As a difference with classical solutions, based on the installation of crowbar circuits, this operation mode permits to keep the inverter connected to the generator, something that would permit the injection of power to the grid during the fault, as the new grid codes demand. A theoretical study of the dynamical behavior of the rotor voltage is also developed, in order to show that the voltage at the rotor terminals required for the control strategy implementation remains under controllable limits. In order to validate the proposed control system simulation, results have been collected using PSCAD/EMTDC and experimental tests have been carried out in a scaled prototype.
In chronic myeloid leukemia (CML) cell lines, brief exposure to pharmacologically relevant dasatinib concentrations results in apoptosis. In this study, we assess the impact of intensity and duration ...of Bcr-Abl kinase inhibition on primary CD34(+) progenitors of chronic phase CML patients. As CML cells exposed to dasatinib in vivo are in a cytokine-rich environment, we also assessed the effect of cytokines (six growth factors cocktail or granulocyte-macrophage colony-stimulating factor (CSF) or granulocyte-CSF) in combination with dasatinib. In the presence of cytokines, short-term intense Bcr-Abl kinase inhibition (>or=90% p-Crkl inhibition) with 100 nM dasatinib did not reduce CD34(+) colony-forming cells (CFCs). In contrast, without cytokines, short-term exposure to dasatinib reduced CML-CD34(+) CFCs by 70-80%. When cytokines were added immediately after short-term exposure to dasatinib, CML-CD34(+) cells remained viable, suggesting that oncogene dependence of these cells can be overcome by concomitant or subsequent exposure to cytokines. Additional inhibition of Janus tyrosine kinase (Jak) activity re-established the sensitivity of CML progenitors to intense Bcr-Abl kinase inhibition despite the presence of cytokines. These findings support the contention that therapeutic strategies combining intense Bcr-Abl kinase inhibition and blockade of cytokine signaling pathways can be effective for eradication of CML progenitors.
The Laser Interferometer Gravitational Wave Observatory (LIGO) consists of two widely separated 4 km laser interferometers designed to detect gravitational waves from distant astrophysical sources in ...the frequency range from 10 Hz to 10 kHz. The first observation run of the Advanced LIGO detectors started in September 2015 and ended in January 2016. A strain sensitivity of better than 10 super(-23)/radicalHz was achieved around 100 Hz. Understanding both the fundamental and the technical noise sources was critical for increasing the astrophysical strain sensitivity. The average distance at which coalescing binary black hole systems with individual masses of 30Mmiddot could be detected above a signal-to-noise ratio (SNR) of 8 was 1.3 Gpc, and the range for binary neutron star inspirals was about 75 Mpc. With respect to the initial detectors, the observable volume of the Universe increased by a factor 69 and 43, respectively. These improvements helped Advanced LIGO to detect the gravitational wave signal from the binary black hole coalescence, known as GW150914.
The functional activity of the organic cation transporter 1 (OCT-1) protein (OCT-1 activity) is an excellent predictor of molecular response and progression-free survival in patients with newly ...diagnosed chronic phase chronic myeloid leukemia treated with imatinib as front-line therapy.
In this study the predictive value of OCT-1 activity in patients treated with imatinib 400 mg/day or 800 mg/day was evaluated in relation to trough imatinib plasma levels assessed in 100 patients enrolled in the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) trial.
The rate of major molecular responses by 24 months in patients on imatinib 400 mg/day was significantly higher in those with high OCT-1 activity than in those with low OCT-1 activity (low OCT-1 activity, 57% of patients; high OCT-1 activity, 100%; P < 0.001); the corresponding difference in patients treated with imatinib 800 mg/day did not reach statistical significance (low OCT-1 activity, 68%; high OCT-1 activity, 95%; P = 0.073). In addition, the combination of low trough imatinib levels (< 1200 ng/mL) and low OCT-1 activity defined a group of patients who had the lowest rates of major molecular response (47%) by 24 months compared to all other patients (81%, P = 0.009). These patients were also at the highest risk of failed imatinib therapy when compared to all other patients (P<0.001).
High-dose imatinib leads to superior molecular responses in patients with low OCT-1 activity. In this group trough imatinib levels may define a group with inferior outcomes. Among patients with high OCT-1 activity, neither higher imatinib dose nor monitoring imatinib trough levels was found to be of significant clinical value. Hence OCT-1 activity determined prior to the start of therapy in newly diagnosed CML patients provides a valuable prognostic tool to determine the optimal up-front dose of imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia.
Summary
Determinants of trabecular bone score (TBS) and vertebral fractures assessed semiquantitatively (SQ1–SQ3) were studied in 496 women with fragility fractures. TBS was associated with age, ...parental hip fracture, alcohol intake and BMD, not SQ1–SQ3 fractures. SQ1–SQ3 fractures were associated with age, prior fractures, and lumbar spine BMD, but not TBS.
Introduction
Trabecular bone score (TBS) and vertebral fractures assessed by semiquantitative method (SQ1–SQ3) seem to reflect different aspects of bone strength. We therefore sought to explore the determinants of and the associations between TBS and SQ1–SQ3 fractures.
Methods
This cross-sectional sub-study of the Norwegian Capture the Fracture Initiative included 496 women aged ≥ 50 years with fragility fractures. All responded to a questionnaire about risk factors for fracture, had bone mineral density (BMD) of femoral neck and/or lumbar spine assessed, TBS calculated, and 423 had SQ1–SQ3 fracture assessed.
Results
Mean (SD) age was 65.6 years (8.6), mean TBS 1.27 (0.10), and 33.3% exhibited SQ1–SQ3 fractures. In multiple variable analysis, higher age (β
per SD
= − 0.26, 95% CI: − 0.36,− 0.15), parental hip fracture (β = − 0.29, 95% CI: − 0.54,− 0.05), and daily alcohol intake (β = − 0.43, 95% CI − 0.79, − 0.08) were associated with lower TBS. Higher BMD of femoral neck (β
per SD
= 0.34, 95% CI 0.25–0.43) and lumbar spine (β
per SD
= 0.40, 95% CI 0.31–0.48) were associated with higher TBS. In multivariable logistic regression analyses, age (OR
per SD
= 1.94, 95% CI 1.51–2.46) and prior fragility fractures (OR = 1.71, 95% CI 1.09–2.71) were positively associated with SQ1–SQ3 fractures, while lumbar spine BMD (OR
per SD
= 0.75 95% CI 0.60–0.95) was negatively associated with SQ1–SQ3 fractures. No association between TBS and SQ1–SQ3 fractures was found.
Conclusion
Since TBS and SQ1–SQ3 fractures were not associated, they may act as independent risk factors, justifying the use of both in post-fracture risk assessment.
In a phase 3 clinical trial involving previously treated patients with advanced renal-cell carcinoma, progression-free survival was significantly longer with the VEGF receptor inhibitor cabozantinib ...than with everolimus (7.4 months vs. 3.8 months).
Renal-cell carcinoma is the most common form of kidney cancer, with more than 330,000 cases diagnosed and more than 140,000 deaths attributed to it worldwide every year.
1
Approximately one third of patients present with metastatic disease at diagnosis,
2
and in about one third of treated patients with localized disease, the disease will relapse.
3
–
5
Inactivation of the von Hippel–Lindau (VHL) tumor-suppressor protein characterizes clear-cell tumors, the predominant histologic subtype in patients with renal-cell carcinoma, and results in the up-regulation of vascular endothelial growth factor (VEGF) production.
6
,
7
Antiangiogenic drugs that target VEGF (bevacizumab) and its receptors (sunitinib, sorafenib, pazopanib, and . . .
Viral lysis of microbial hosts releases organic matter that can then be assimilated by nontargeted microorganisms. Quantitative estimates of virus-mediated recycling of carbon in marine waters, first ...established in the late 1990s, were originally extrapolated from marine host and virus densities, host carbon content and inferred viral lysis rates. Yet, these estimates did not explicitly incorporate the cascade of complex feedbacks associated with virus-mediated lysis. To evaluate the role of viruses in shaping community structure and ecosystem functioning, we extend dynamic multitrophic ecosystem models to include a virus component, specifically parameterized for processes taking place in the ocean euphotic zone. Crucially, we are able to solve this model analytically, facilitating evaluation of model behavior under many alternative parameterizations. Analyses reveal that the addition of a virus component promotes the emergence of complex communities. In addition, biomass partitioning of the emergent multitrophic community is consistent with well-established empirical norms in the surface oceans. At steady state, ecosystem fluxes can be probed to characterize the effects that viruses have when compared with putative marine surface ecosystems without viruses. The model suggests that ecosystems with viruses will have (1) increased organic matter recycling, (2) reduced transfer to higher trophic levels and (3) increased net primary productivity. These model findings support hypotheses that viruses can have significant stimulatory effects across whole-ecosystem scales. We suggest that existing efforts to predict carbon and nutrient cycling without considering virus effects are likely to miss essential features of marine food webs that regulate global biogeochemical cycles.
In patients with renal-cell carcinoma at high risk for relapse after nephrectomy, the rate of disease-free survival was significantly higher among those receiving sunitinib than among those receiving ...placebo, at the cost of a higher rate of toxic events.
Each year, approximately 300,000 persons worldwide are diagnosed with renal-cell carcinoma, resulting in 129,000 deaths.
1
,
2
The prognosis for patients with renal-cell carcinoma is dependent on the stage of disease and other risk factors. The 5-year survival rate is 53% for locoregional (stage III) disease and 8% for metastatic disease.
3
Overall, locoregional disease is diagnosed in 16% of patients with renal-cell carcinoma,
4
and up to 40% of these patients have a relapse with metastasis after nephrectomy.
5
,
6
The relapse risk can be assessed with the use of two validated models, the University of California Los Angeles Integrated Staging System (UISS) . . .
End member mixing analysis (EMMA) is a commonly applied method to identify and quantify the dominant runoff producing sources of water. It employs tracers to determine the dimensionality of the ...hydrologic system. Many EMMA studies have been conducted using two to six tracers, with some of the main tracers being Ca, Na, Cl−, water isotopes, and alkalinity. Few studies use larger tracer sets including minor trace elements such as Li, Rb, Sr, and Ba. None of the studies has addressed the question of the tracer set size and composition, despite the fact that these determine which and how many end members (EM) will be identified. We examine how tracer set size and composition affects the conceptual model that results from an EMMA. We developed an automatic procedure that conducts EMMA while iteratively changing tracer set size and composition. We used a set of 14 tracers and 9 EMs. The validity of the resulting conceptual models was investigated under the aspects of dimensionality, EM combinations, and contributions to stream water. From the 16,369 possibilities, 23 delivered plausible results. The resulting conceptual models are highly sensitive to the tracer set size and composition. The moderate reproducibility of EM contributions indicates a still missing EM. It also emphasizes that the major elements are not always the most useful tracers and that larger tracer sets have an enhanced capacity to avoid false conclusions about catchment functioning. The presented approach produces results that may not be apparent from the traditional approach and it is a first step to add the idea of statistical significance to the EMMA approach.
Key Points
Resulting model of EMMA is highly sensitive to tracer set size and composition
Large tracer sets help to avoid false conclusions about runoff processes
Methodology to add statistical significance to the EMMA approach
Monitoring soil moisture is often necessary in hydrological studies on various scales. One of the challenges is to determine the mean soil moisture of large areas with minimum labour and costs. The ...aim of this study is to test temporal persistence of sample locations to decrease the number of samples required to make reliable estimates of mean moisture content in the top soil. Soil moisture data on four experimental sites were collected during the vegetation period in 2004–2006. The experimental sites are located in a steppe environment in northern China, and are characterised by different grazing management which causes differences in vegetation cover. A total of 100 sampling points per site were ranked with respect to their difference to field mean soil moisture using the time-stability concept. We tested whether: (a) representative sample locations exist that predict field mean soil moisture to an acceptable degree, and (b) these locations are time-stable beyond a single vegetation period. Time-stable locations with a low deviation from mean field soil moisture and low standard deviation were identified for each site. Although the time-stability characteristics of some points varied between years, the selected points were appropriate to predict mean soil moisture of the sites for multiple years. On the field scale, time-stability and the persistence of patterns were analysed by the use of a Spearman rank correlation. The analysis showed that persistence depended on grazing management and the related plant cover. It is concluded that the time-stability concept provides useful information for the validation of hydrological or remote sensing models, or for the upscaling of soil moisture information to larger scales. A preliminary comparison of soil moisture measurements derived from ground-truth and remote sensing data showed that the data matched well in some cases, but that the considerable difference in spatial extent promotes differences in other cases.
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