To effectively keep pace with the global IP traffic growth forecasted in the years to come, flex-grid over multi-core fiber (MCF) networks can bring superior spectrum utilization flexibility, as well ...as bandwidth scalability far beyond the non-linear Shannon's limit. In such a network scenario, however, full node switching re-configurability will require enormous node complexity, pushing the limits of current optical device technologies with prohibitive capital expenditures. Therefore, cost-effective node solutions will most probably be the key enablers of flex-grid/MCF networks, at least in the short- and mid-term future. In this context, this paper proposes a cost-effective reconfigurable optical add/drop multiplexer (ROADM) architecture for flex-grid/MCF networks, called CCC-ROADM, which reduces technological requirements (and associated costs) in exchange for demanding core continuity along the end-to-end communication. To assess the performance of the proposed CCC-ROADM in comparison with a fully flexible ROADM (i.e., a fully non-blocking ROADM, called FNB-ROADM in this work) in large-scale network scenarios, a novel lightweight heuristic to solve the route, modulation, core, and spectrum assignment problem in flex-grid/MCF networks is presented in this work, whose goodness is successfully validated against optimal ILP formulations previously proposed for the same goal. The obtained numerical results in a significant number of representative network topologies with different MCF configurations of 7, 12, and 19 cores show almost identical network performance in terms of maximum network throughput when deploying CCC-ROADMs versus FNB-ROADMs, while decreasing network capital expenditures to a large extent.
The first examples of dihydro-1H-benzindoles by enantioselective γ-lactamization reaction of naphthyl sulfilimines with trichloroacetyl chloride in the presence of ZnCu as catalyst (≥98:2 er and ...65-80% yields) are described. Products are obtained by 3,3-sigmatropic rearrangement of the azasulfonium enolate or followed by a second allylic rearrangement that transfers chirality. The absolute stereochemistry was confirmed by X-ray crystallography, which provides support for the mechanisms proposed.
Even though time-to-treatment has been shown to be a determinant of mortality in primary angioplasty, the potential benefits from early pharmacological reperfusion by glycoprotein (Gp) IIb-IIIa ...inhibitors are still unclear. The aim of this meta-analysis was to combine individual data from all randomised trials conducted on facilitated primary angioplasty by the use of early Gp IIb-IIIa inhibitors.
The literature was scanned by formal searches of electronic databases (MEDLINE, EMBASE) from January 1990 to October 2007. All randomised trials on facilitation by the early administration of Gp IIb-IIIa inhibitors in ST-segment elevation myocardial infarction (STEMI) were examined. No language restrictions were enforced. Individual patient data were obtained from 11 out of 13 trials, including 1662 patients (840 patients (50.5%) randomly assigned to early and 822 patients (49.5%) to late Gp IIb-IIIa inhibitor administration). Preprocedural Thrombolysis in Myocardial Infarction Study (TIMI) grade 3 flow was more frequent with early Gp IIb-IIIa inhibitors. Postprocedural TIMI 3 flow and myocardial blush grade 3 were higher with early Gp IIb-IIIa inhibitors but did not reach statistical significance except for abciximab, whereas the rate of complete ST-segment resolution was significantly higher with early Gp IIb-IIIa inhibitors. Mortality was not significantly different between groups, although early abciximab demonstrated improved survival compared with late administration, even after adjustment for clinical and angiographic confounding factors.
This meta-analysis shows that pharmacological facilitation with the early administration of Gp IIb-IIIa inhibitors in patients undergoing primary angioplasty for STEMI is associated with significant benefits in terms of preprocedural epicardial recanalisation and ST-segment resolution, which translated into non-significant mortality benefits except for abciximab.
Near-record warmth over much of the United States during March 2007 promoted early growth of crops and vegetation. A widespread arctic air outbreak followed in early April, resulting in extensive ...agricultural losses over much of the south-central and southeastern US. This ‘false spring’ event also resulted in widespread damage to newly grown tissues of native deciduous forest species, shown by previous researchers to have had measurable effects on the terrestrial carbon cycle. The current study reconstructed the historical occurrence of false springs over most of the southeastern quarter of the conterminous US (32–39°N; 75–98°W) from 1901 to 2007 using daily maximum and minimum temperature records from 176 stations in the Global Historical Climatology Network database, and enhanced vegetation index (EVI) data derived from Moderate Resolution Imaging Spectroradiometer (MODIS) satellite observations. A false spring index was derived that examined the timing of the start of the growing season (SGS), or leaf emergence, relative to the timing of a potentially damaging last hard freeze (minimum temperature ≤ − 2.2 °C). SGS was modeled for the domain by combining EVI data with ground-based temperature ‘degree day’ calculations reflecting the rate of springtime warming. No significant area-wide, long-term SGS trend was found; however, over much of a contiguous region stretching from Mississippi eastward to the Carolinas, the timing of the last hard freeze was found to occur significantly later, this change occurring along with increased frequency of false springs. Earlier last hard freeze dates and decreased frequency of false springs were found over much of the northwestern part of the study region, including Arkansas and southern Missouri.
Background
Ovarian cancer is the most lethal of all gynecological cancers. Cancer Antigen 125 (CA125) is the best‐performing ovarian cancer biomarker which however is still not effective as a ...screening test in the general population. Recent literature reports additional biomarkers with the potential to improve on CA125 for early detection when using longitudinal multimarker models.
Methods
Our data comprised 180 controls and 44 cases with serum samples sourced from the multimodal arm of UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Our models were based on Bayesian change‐point detection and recurrent neural networks.
Results
We obtained a significantly higher performance for CA125–HE4 model using both methodologies (AUC 0.971, sensitivity 96.7% and AUC 0.987, sensitivity 96.7%) with respect to CA125 (AUC 0.949, sensitivity 90.8% and AUC 0.953, sensitivity 92.1%) for Bayesian change‐point model (BCP) and recurrent neural networks (RNN) approaches, respectively. One year before diagnosis, the CA125–HE4 model also ranked as the best, whereas at 2 years before diagnosis no multimarker model outperformed CA125.
Conclusions
Our study identified and tested different combination of biomarkers using longitudinal multivariable models that outperformed CA125 alone. We showed the potential of multivariable models and candidate biomarkers to increase the detection rate of ovarian cancer.
Using the data from largest prospective ovarian cancer clinical trial, we assessed, for the first time, the performance of deep and statistical learning approaches in evaluating of the panel longitudinal biomarkers. Our results demonstrate that these models outperform CA125, the single best ovarian cancer biomarker. These findings underscore the potential of multimarker models in improving the detection rate of ovarian cancer and have significant implications for the field of cancer screening and early detection.
Understanding the evolutionary dynamics of the Coronavirus disease 2019 (COVID-19) pandemic in the coming months is a matter of great importance and urgency for governments worldwide, making ...fundamental decisions based on what is known about the transmission mechanisms of the virus and its survival in the environment. The present study aimed to evaluate the impact of demographic variables, solar radiation and relative humidity on the spread of the COVID-19 pandemic of the various regions in Italy.
The retrospective longitudinal study was conducted, and data used in this study was obtained from the Italian Health Ministry. Descriptive statistics included mean, frequency, and percentage, and results presented by graphs were calculated.
The infection trend was investigated by comparing it with the demographic situation and the irradiation indices of solar ultraviolet light that are detected with the changing seasons. The present study reported that the geographic areas with higher population density and lower solar radiation during the autumn and winter months were most affected by SARS-CoV-2.
The analysis carried out can provide a predictive model for the future phases of the COVID-19 pandemic in Italy, regardless of the adoption of lockdown measures and behavioral factors.
•An application for mobile devices is presented, compatible with almost all versions of Android O.S.•It calculates the best combination of fertilizers for fertigation, minimizing fertilizers ...cost.•The Simplex algorithm is used to solve the problem, due to its low computational cost.•It uses a list of commercial fertilizers hosted in a DDBB in the Cloud updated daily.•A local DDBB permits to store and manage calculations, and to send them by e-mail.
In the agriculture sector, the efficient management of fertilizers is reflected into a saving of money and time. Many software developments are found in the scientific literature and in the market that optimize the performance and use of fertilizers for specific crops. Most of them do not take into account the current price of fertilizers; and others show a high computational cost, which means high time to solve scenarios with medium–high number of fertilizers to select and high power consumption, being not suitable for mobile devices. In this work Ecofert is presented as a simple and powerful software application developed for Android O.S. that calculates the best combination of fertilizers to obtain the desired nutrient solution for different crops, taking into account the current price of fertilizers in the market. The main novelties of Ecofert is, on the one hand, that it solves the fertilization selection by modeling this as a Linear Programming problem, and using specific mathematical libraries to solve it. On the other hand, Ecofert works with a list of commercial fertilizers hosted in a Data Base in the Cloud, where the composition and price (in Euro) is updated daily. Moreover Ecofert shows a low computational cost, even for large number of fertilizers (>20). Its simplicity permits Ecofert to be executed in mobile devices, giving farmers and agriculture technicians a powerful tool to support agricultural tasks in situ.
Increased Rho kinase (ROCK) activity contributes to smooth muscle contraction and regulates blood pressure homeostasis. We hypothesized that potent and selective ROCK inhibitors with novel structural ...motifs would help elucidate the functional role of ROCK and further explore the therapeutic potential of ROCK inhibition for hypertension. In this article, we characterized two aminofurazan-based inhibitors, GSK269962A N-(3-{2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-1H-imidazo4, 5-cpyridin-6-yloxy}phenyl)-4-{2-(4-morpholinyl)ethyl-oxy}benzamide and SB-7720770-B 4-(7-{(3S)-3-amino-1-pyrrolidinylcarbonyl}-1-ethyl-1H-imidazo4,5-cpyridin-2-yl)-1,2,5-oxadiazol-3-amine, as members of a novel class of compounds that potently inhibit ROCK enzymatic activity. GSK269962A and SB-772077-B have IC50 values of 1.6 and 5.6 nM toward recombinant human ROCK1, respectively. GSK269962A also exhibited more than 30-fold selectivity against a panel of serine/threonine kinases. In lipopolysaccharide-stimulated monocytes, these inhibitors blocked the generation of inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-alpha. Furthermore, both SB-772077-B and GSK269962A induced vasorelaxation in preconstricted rat aorta with an IC50 of 39 and 35 nM, respectively. Oral administration of either GSK269962A or SB-772077-B produced a profound dose-dependent reduction of systemic blood pressure in spontaneously hypertensive rats. At doses of 1, 3, and 30 mg/kg, both compounds induced a reduction in blood pressure of approximately 10, 20, and 50 mm Hg. In addition, administration of SB-772077-B also dramatically lowered blood pressure in DOCA salt-induced hypertensive rats. SB-772077-B and GSK269962A represent a novel class of ROCK inhibitors that have profound effects in the vasculature and may enable us to further evaluate the potential beneficial effects of ROCK inhibition in animal models of cardiovascular as well as other chronic diseases.
Lead optimization of piperidine amide HTS hits, based on an anilino-thiazole core, led to the identification of analogs which displayed low nanomolar blocking activity at the canonical transient ...receptor channels 3 and 6 (TRPC3 & 6) based on FLIPR (carbachol stimulated) and electrophysiology (OAG stimulated) assays. In addition, the anilino-thiazole amides displayed good selectivity over other TRP channels (TRPA1, TRPV1, and TRPV4), as well as against cardiac ion channels (CaV1.2, hERG, and NaV1.5). The high oxidation potential of the aliphatic piperidine and aniline groups, as well as the lability of the thiazole amide group contributed to the high clearance observed for this class of compounds. Conversion of an isoquinoline amide to a naphthyridine amide markedly reduced clearance for the bicyclic piperidines, and improved oral bioavailability for this compound series, however TRPC3 and TRPC6 blocking activity was reduced substantially. Although the most potent anilino-thiazole amides ultimately lacked oral exposure in rodents and were not suitable for chronic dosing, analogs such as 14–19, 22, and 23 are potentially valuable in vitro tool compounds for investigating the role of TRPC3 and TRPC6 in cardiovascular disease.
This paper presents a new technique in voltage balancing for single-phase railway substations. Using the concept of chopper-controlled impedance, the authors study the feasibility of an active ...Steinmetz circuit based on ac choppers. The low power losses in semiconductor devices make the proposed topology an interesting alternative to classical solutions such as those based on voltage source inverters. Design criteria are presented using information obtained from measurements carried out on a substation of the French National Railways. Finally, the study is validated by means of simulations and experimental results carried out on a 1.5 kVA prototype.
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