STABILITY-INDICATING LIQUID CHROMATOGRAPHY METHOD FOR THE DETERMINATION OF PENTOXYVERINE CITRATE AND ITS DEGRADANT

Objectives: The objectives of this research were to develop and validate a HPLC method for determination of Pentoxyverine citrate (PNX) and its degradant (DG). Methods: Forced degradation studies were performed on bulk sample using alkaline (0.1M sodium hydroxide) and acid (1M hydrochloric acid. The proposed method was based on using a 150 x 4.6 mm (i. d.) (Luna, Phenomenex, Torrance, CA, USA) (5 µm particle size) reversed phase C18 column with mobile phase consisting of a mixture of methanol-10 mM sodium dihydrogen phosphate pH 4 in ratio of (60:40, v/v) and UV detection at 230 nm with flow rate of 1 mL min-1. Results: The linear calibration range was between 10-40 mg ml-1and 10-40 mg ml-1for PNX and DG respectively. The method was found to be accurate with 100.23% and 100.07% recovery for PNX and DG respectively. The limit of detection (LOD) was found to be 3.79 x10-2μg ml-1 and 4.24 x10-2μg ml-1 for PNX and DG respectively, while the limit of quantification (LOQ) was found to be 12.62 x10-2μg ml-1 and 14.12 x10-2μg ml-1 for PNX and DG respectively. PNX was found to be most stable at a pH of 5.7. Conclusion: The validation study of the proposed method was successfully carried out and the method was found to be suitable and economic for routine determination of PNX in pharmaceutical syrup, without any interference from the excipients, and in the presence of its acidic and alkaline degradation products

Properties of electrons scattered on a strong plane electromagnetic wave with a linear polarization: classical treatment

The relations among the components of the exit momenta of ultrarelativistic electrons scattered on a strong electromagnetic wave of a low (optical) frequency and linear polarization are established using the exact solutions to the equations of motion with radiation reaction included (the Landau-Lifshitz equation). It is found that the momentum components of the electrons traversed the electromagnetic wave depend weakly on the initial values of the momenta. These electrons are mostly scattered at the small angles to the direction of propagation of the electromagnetic wave. The maximum Lorentz factor of the electrons crossed the electromagnetic wave is proportional to the work done by the electromagnetic field and is independent of the initial momenta. The momentum component parallel to the electric field strength vector of the electromagnetic wave is determined only by the diameter of the laser beam measured in the units of the classical electron radius. As for the reflected electrons, they for the most part lose the energy, but remain relativistic. There is a reflection law for these electrons that relates the incident and the reflection angles and is independent of any parameters.Comment: 12 pp, 3 fig

Phase II randomized preoperative window-of-opportunity study of the PI3K inhibitor pictilisib plus anastrozole compared with anastrozole alone in patients with estrogen receptor-positive breast cancer

Purpose: Preclinical data support a key role for the PI3K pathway in estrogen receptor-positive breast cancer and suggest that combining PI3K inhibitors with endocrine therapy may overcome resistance. This preoperative window study assessed whether adding the PI3K inhibitor pictilisib (GDC-0941) can increase the antitumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy. Patients and Methods: In this randomized, open-label phase II trial, postmenopausal women with newly diagnosed operable estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers were recruited. Participants were randomly allocated (2:1, favoring the combination) to 2 weeks of preoperative treatment with anastrozole 1 mg once per day (n = 26) or the combination of anastrozole 1 mg with pictilisib 260 mg once per day (n = 49). The primary end point was inhibition of tumor cell proliferation as measured by change in Ki-67 protein expression between tumor samples taken before and at the end of treatment. Results: There was significantly greater geometric mean Ki-67 suppression of 83.8% (one-sided 95% CI, ≥ 79.0%) for the combination and 66.0% (95% CI, ≤ 75.4%) for anastrozole (geometric mean ratio [combination: anastrozole], 0.48; 95% CI, ≤ 0.72; P = .004). PIK3CA mutations were not predictive of response to pictilisib, but there was significant interaction between response to treatment and molecular subtype (P =.03);for patients with luminal B tumors, the combination:anastrozole geometric mean ratio of Ki-67 suppression was 0.37 (95% CI, ≤ 0.67; P = .008), whereas no significant Ki-67 response was observed for pictilisib in luminal A tumors (1.01; P = .98). Multivariable analysis confirmed Ki-67 response to the combination treatment of patients with luminal B tumors irrespective of progesterone receptor status or baseline Ki-67 expression. Conclusion: Adding pictilisib to anastrozole significantly increases suppression of tumor cell proliferation in luminal B primary breast cancer

A Novel Fast Neutron Detector For Nuclear Data Measurements

International audienceAccelerator driven system will use a heavy element target such as lead. Many calculations are available to simulate high-energy spallation neutron induced reactions, but little data are available for comparison with the simulations. In order to constrain the simulation tools we have measured (n,Xn) double differential cross section on different targets at The Svedberg Laboratory, Uppsala, Sweden. For neutron energy above 40 MeV, we have developed a novel detector, CLODIA, based on proton recoil and drift chambers to determine neutron energy. CLODIA (Chamber for LOcalization with DrIft and Amplification) is able to track recoil protons with energy up to 90 MeV with spatial resolution of about one millimeter and a detection efficiency of 99% for each drift chamber. Using CLODIA coupled with the SCANDAL set-up, we have been able to measure double differential (n,Xn) cross section on lead and iron for incident neutron energy in the 40-95 MeV energy region

A Better-response Strategy for Self-interested Planning Agents

[EN] When self-interested agents plan individually, interactions that prevent them from executing their actions as planned may arise. In these coordination problems, game-theoretic planning can be used to enhance the agents¿ strategic behavior considering the interactions as part of the agents¿ utility. In this work, we define a general-sum game in which interactions such as conflicts and congestions are reflected in the agents¿ utility. We propose a better-response planning strategy that guarantees convergence to an equilibrium joint plan by imposing a tax to agents involved in conflicts. We apply our approach to a real-world problem in which agents are Electric Autonomous Vehicles (EAVs). The EAVs intend to find a joint plan that ensures their individual goals are achievable in a transportation scenario where congestion and conflicting situations may arise. Although the task is computationally hard, as we theoretically prove, the experimental results show that our approach outperforms similar approaches in both performance and solution quality.This work is supported by the GLASS project TIN2014-55637-C2-2-R of the Spanish MINECO and the Prometeo project II/2013/019 funded by the Valencian Government.Jordán, J.; Torreño Lerma, A.; De Weerdt, M.; Onaindia De La Rivaherrera, E. (2018). A Better-response Strategy for Self-interested Planning Agents. Applied Intelligence. 48(4):1020-1040. https://doi.org/10.1007/s10489-017-1046-5S10201040484Aghighi M, Bäckström C (2016) A multi-parameter complexity analysis of cost-optimal and net-benefit planning. In: Proceedings of the Twenty-Sixth International Conference on International Conference on Automated Planning and Scheduling. AAAI Press, London, pp 2–10Bercher P, Mattmüller R (2008) A planning graph heuristic for forward-chaining adversarial planning. 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Artif Intell 174(1):20–50Fabrikant A, Papadimitriou C, Talwar K (2004) The complexity of pure nash equilibria. In: Proceedings of the thirty-sixth annual ACM symposium on theory of computing, STOC ’04, pp 604–612Friedman JW, Mezzetti C (2001) Learning in games by random sampling. J Econ Theory 98(1):55–84Ghallab M, Nau D, Traverso P (2004) Automated planning: theory & practice. ElsevierGoemans M, Mirrokni V, Vetta A (2005) Sink equilibria and convergence. In: Proceedings of the 46th annual IEEE symposium on foundations of computer science, FOCS ’05, pp 142–154Hadad M, Kraus S, Hartman IBA, Rosenfeld A (2013) Group planning with time constraints. Ann Math Artif Intell 69(3):243–291Hart S, Mansour Y (2010) How long to equilibrium? the communication complexity of uncoupled equilibrium procedures. Games and Economic Behavior 69(1):107–126Helmert M (2003) Complexity results for standard benchmark domains in planning. 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Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Ventricular-arterial uncoupling in heart failure with preserved ejection fraction after myocardial infarction in dogs - invasive versus echocardiographic evaluation

Heart failure with preserved left ventricular ejection fraction and abnormal diastolic function is commonly observed after recovery from an acute myocardial infarction. The aim of this study was to investigate the physiopathology of heart failure with preserved ejection fraction in a model of healed myocardial infarction in dogs.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe