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The PI3K/Akt/m TOR pathway in ovarian cancer: therapeutic opportunities and challenges

Chinese Journal of Cancer 2015年第1期34卷 4-16页

作者： bianca cheaib Aurélie Auguste Alexandra Leary Gynecological Unit Department of MedicineGustave Roussy Comprehensive Cancer Centre Gynecological Tumor Team Translational Research Laboratory U981 Gustave Roussy Comprehensive Cancer Centre

The phosphatidylinositol 3 kinase(PI3K) pathway is frequently altered in cancer, including ovarian cancer(OC). Unfortunately, despite a sound biological rationale and encouraging activity in preclinical models, trials of first-generation inhibitors of mammalian target of rapamycin(m TOR) in OC have demonstrated negative results. The lack of patient selection as well as resistance to selective m TOR complex-1(m TORC1) inhibitors could explain the disappointing results thus far. Nonetheless, a number of novel agents are being investigated, including dual m TORC1/m TORC2, Akt, and PI3 K inhibitors. Although it is likely that inhibition of the PI3K/Akt/m TOR pathway may have little effect in unselected OC patients, certain histological types, such as clear cell or endometrioid OC with frequent phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit alpha(PIK3CA) and/or phosphatase and tensin homolog(PTEN) alterations, may be particularly suited to this approach. Given the complexity and redundancy of the PI3 K signaling network, PI3 K pathway inhibition may be most useful in combination with either chemotherapy or other targeted therapies, such as MEK inhibitors, anti-angiogenic therapy, and hormonal therapy, in appropriately selected OC patients. Here, we discuss the relevance of the PI3 K pathway in OC and provide an up-to-date review of clinical trials of novel PI3 K inhibitors alone or in combination with cytotoxics and novel therapies in OC. In addition, the challenges of drug resistance and predictive biomarkers are addressed.

关键词： mTOR 信号通路卵巢癌磷脂酰肌醇3激酶 AKT 激素疗法治疗临床试验

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PERFORMANCE EVALUATION OF DISCRETE EVENT SYSTEMS INVOLVING HENSTOCK-KURZWEIL INTEGRAL

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Journal of Systems Science and Systems Engineering 2009年第2期18卷 243-256页

作者： Calin CIUFUDEAN bianca SATCO "Stefan cel Mare"University of Suceava 9 University str720225SuceavaRomania

This paper presents a study on the performance of flexible manufacturing systems （FMSs）, by using discrete event system （DES） models, considering resource losses modelled by a parameter entitled coverage factor. We conclude that the resources cell loss distribution between the tasks of a FSM is a real function that cannot be integrated, in order to calculate its primitive, in the classical sense of Riemann or Lebesgue, but only in the sense of Henstock-Kurzweil integral. Our result allows one to study more general processes where highly oscillatory functions occur. The method used to deduce the functi6n describing the resources cell loss distribution is compared with a classical method related in the literature, respectively rational interpolants. An example has been constructed to emphasize what we believe to be, new approaches.

关键词： Discrete-event system Henstock-Kurzweil integral rare event flexible manufacturing system distributed system coverage factor

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Recovering Navier–Stokes Equations from Asymptotic Limits of the Boltzmann Gas Mixture Equation

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Communications in Theoretical Physics 2016年第5期65卷 553-562页

作者： Carlo bianca Christian Dogbe Laboratoire de Physique Statistique Ecole Normale Superieure PSL Research University University Paris Diderot Sorbonne Paris-Cite Sorbonne Universites UPMC Univ Paris 06 CNRS Department of Mathematics Universite de Caen Normandie LMNOCNRS

This paper is devoted to the derivation of macroscopic fluid dynamics from the Boltzmann mesoscopic dynamics of a binary mixture of hard-sphere gas *** the hydrodynamics limit is performed by employing different time and space *** paper shows that,depending on the magnitude of the parameters which define the scaling,the macroscopic quantities(number density,mean velocity and local temperature)are solutions of the acoustic equation,the linear incompressible Euler equation and the incompressible Navier–Stokes *** derivation is formally tackled by the recent moment method proposed by[***,et al.,***.63(1991)323]and the results generalize the analysis performed in[***,et al.,*** ***.29(2015)240].

关键词： gas mixtures hydrodynamic limit asymptotic limit fluid equation conservation law

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Summary of Italian marine stages of the Quaternary

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Episodes 2008年第2期31卷 251-254页

作者： Maria bianca Cita Universita di Milano Dipartimento di Scienze della Terra ＂Ardito Desio＂via Mangiagalli 34 20133 Milano Italy.

Eight marine stages for the Quaternary have been defined in Italy starting from 1872 （Sicilian of Doderlein） to 1979 （Selinuntian of Ruggieri and Sprovieri）. The definition of all these stages was based essentially on invertebrate paleontology, initially from the study of pelecypods and gastropods, but also of corals, ostracods, benthic foraminifers and, more recently, on planktonic foraminifers and calcareous nannofossils. The 1948 International Geological Congress held in London decided to search for a locality in Italy to define the Neogene/Quaternary boundary in correspondence with the first appearance of the ＂northern guests＂ in the Mediterranean. The Vrica section of Calabria was selected for defining the GSSP of the Pleistocene in 1984.

关键词：地球第四纪地质时代意大利航海业

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Modeling the antigen recognition by B-cell and T-cell receptors through thermostatted kinetic theory methods

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International Journal of Biomathematics 2017年第5期10卷 263-299页

作者： Carlo bianca Louis Brezin Laboratoire de Recherche en Eco-innovation Industrielle el Energetique ECAM-EPMI 13 Boulevard de l'Hautil 95092 Cergy Pontoise Cedex France Laboratoire de Physique Statistique Ecole Normale Supdrieure PSL Research University Universite Paris Diderot Sorbonne Paris-Cite Sorbonne Universites UPMC Univ Paris 06 CNRS 24 rue Lhomond 75005 Paris France Institut Universitaire de Cancdrologie Facultg de Medecine Universite Pierre et Marie Curie-Paris 6 91 Bd de l'Hopital 75013 Paris France

The activation and the resulting response of the immune system to antigens comprise different complex processes and cells. This paper aims at modeling the processes of recognition and learning of the immune system by means of the thermostatted kinetic theory methods. Specifically, the thermostatted kinetic framework is firstly generalized for taking into account that in some processes of proliferation of the cells, the rate is also function of the degree of information exchanged amongst cells. In particular, within the new framework, a mathematical model is proposed for miming the recognition process of the immune system through the definition of interactions between the cytoto^ic and humoral components of the adaptive immune system via T- and B-cells. The model validation is obtained by performing a sensitivity analysis on the parameters which depicts the main emerging phenomena and the different phases of the recognition and learning of the immune system.

关键词： Thermostatted kinetic theory integro-differential models learning and memory biological complexity immune system.

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Instrumental and bio-monitoring of heavy metal and nanoparticle emissions from diesel engine exhaust in controlled environment

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Journal of Environmental Sciences 2010年第9期22卷 1357-1363页

作者： Simonetta Giordano Paola Adamo Valeria Spagnuolo bianca Maria Vaglieco Department of Structural and Functional Biology University of Naples Federico II Department of Soil Plant Environment and Animal Production Sciences University of Naples Federico II Istituto Motori CNR Via Marconi 8 I-80125 Napoli Italy

In the present article we characterized the emissions at the exhaust of a Common Rail （CR） diesel engine, representative of lightduty class, equipped with a catalyzed diesel particulate filter （CDPF） in controlled environment. The downstream exhausts were directly analyzed （for PM, CO, CO/, Oz, HCs, NOx） by infrared and electrochemical sensors, and SEM-EDS microscope; heavy metals were chemically analyzed using mosses and lichens in bags, and glass-fibre filters all exposed at the engine exhausts. The highest particle emission value was in the 7-54 nm size range; the peak concentration rose until one order of magnitude for the highest load and speed. Particle composition was mainly carbonaceous, associated to noticeable amounts of Fe and silica fibres. Moreover, the content of Cu, Fe, Na, Ni and Zn in both moss and lichen, and of A1 and Cr in moss, was significantly increased. Glass-fibre filters were significantly enriched in A1, B, Ba, Cu, Fe, Na, and Zn. The role of diesel engines as source of carbonaceous nanoparticles has been confirmed, while further investigations in controlled environment are needed to test the catalytic muffler as a possible source of silica fibres considered very hazardous for human health.

关键词： common rail diesel engine exhaust and non-exhaust emissions moss and lichen bags particulate matter

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A novel paradigm for feedback control in LPBF:layer-wise correction for overhang structures

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Advances in Manufacturing 2022年第2期10卷 326-344页

作者： Ema Vasileska Ali Gokhan Demir bianca Maria Colosimo Barbara Previtali Department of Mechanical Engineering Polytechnic University of MilanVia La Masa 120156 MilanItaly

In laser powder bed fusion(LPBF),it is common practice to select process parameters to achieve high density parts starting from simple geometries such as cubes or ***,additive manufacturing is usually adopted to producevery complex geometries,where parameters should be tuned locally,depending on the local features to be *** fact,geometrical features,such as overhangs,acute corners,and thin walls may lead to over-or under-heating conditions,which may result in geometrical inaccuracy,high roughness,volumetric errors(i.e.,porosity)oreven job failure due to *** work proposes a layer-wise control strategy to improve the geometrical precision of overhanging regions using a coaxial melt pool monitoring *** meltpool images acquired at each layer are used in a controlloop toadapt theprocess parameters locally at the next layer in order to minimize surface *** particular,the laser duty cycle is used as a controllable parameterto correct the energy *** work presents the main architecture of the proposed approach,the control strategy and the experimental procedure that need to be applied to design the control *** layer-wise control strategy was tested on AISI 316L stainless steel using an open LPFB *** results showed that the proposed layer-wise control solution results in a constant melt pool observed via the laser heated area size starting from the second layer onward,leading to a significant improvement in the geometrical accuracy of 5 mm-long bridge geometries.

关键词： Closed-loop control Melt pool monitoring:Defect correction Pulsed-wave emission

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Dual Targeting of a Mitochondrial Protein： The Case Study of Cytochrome C1

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Molecular Plant 2011年第4期4卷 679-687页

作者： Anja Rodiger bianca Baudisch Uwe Langner Ralf Bernd Klosgen Institute of Biology--Plant Physiology Martin Luther University Halle-Wittenberg Weinbergweg 10 06120 Halle/Saale Germany

As a result of the endosymbiotic gene transfer, the majority of proteins of mitochondria and chloroplasts is encoded in the nucleus and synthesized in the cytosol as precursor molecules carrying N-terminal transit peptides for the transport into the respective target organelle. In most instances, transport takes place into either mitochondria or chloroplasts, although a few examples of dual targeting into both organelles have been described. Here, we show by a combination of three different experimental strategies that also cytochrome c1 of potato, a component of the respiratory electron transport chain, is imported not only into mitochondria, but also into plastids. In organello import experiments with isolated mitochondria and chloroplasts, which were analyzed in both single and mixed organelte assays, demonstrate that the processing products accumulating after import within the two endosymbiotic organelles are different in size. Dual targeting of cytochrome c1 is observed also in vivo, after biolistic transformation of leaf epidermal cells with suitable reporter constructions. Finally, Western analyses employing cytochrome c1-specific antiserum provide evidence that the protein accumulates in significant amounts in mitochondria and chloroplasts of both pea and spinach. The possible consequences of our findings on the relevance of the dual targeting phenomenon are discussed.

关键词： Protein transport dual targeting cytochrome c1 mitochondria chloroplast.

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Etiologies of Splenic Venous Hypertension:A Review

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Journal of Clinical and Translational Hepatology 2024年第6期12卷 594-606页

作者： Jasmine Tidwell bianca Thakkar George Y.Wu Department of Medicine University of Connecticut Health CenterFarmingtonCTUSA Division of Gastroenterology-Hepatology University of Connecticut Health CenterFarmingtonCTUSA

Splenic venous hypertension or left-sided portal hypertension is a rare condition caused by an obstruction of the splenic ***,it presents with upper gastrointestinal bleeding in the absence of liver *** can be classified based on the mechanism of development of splenic vein hypertension:compression,stenosis,inflammation,thrombosis,and surgically decreased splenic venous *** is established by various imaging modalities and should be suspected in patients with gastric varices in the absence of esophageal varices,splenomegaly,or *** management and prognosis vary depending on the underlying etiology but generally involve reducing splenic venous *** aim of this review was to summarize the etiologies of splenic venous hypertension according to the mechanism of development.

关键词： Splenic venous hypertension Left-sided portal hypertension Sinistral portal hypertension Splenic vein thrombosis Gastric varices Hematemesis Upper gastrointestinal bleeding

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Fatality in Kikuchi-Fujimoto disease: A rare phenomenon

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World Journal of Clinical Cases 2017年第2期5卷 35-39页

作者： bianca Barbat Ruby Jhaj Daniyeh Khurram Providence-Providence Park Hospital

Kikuchi-Fujimoto disease(KFD), also known as histiocytic necrotizing lymphadenitis, is an uncommon condition, typically characterized by lymphadenopathy and fevers. It usually has a benign course; however, it may progress to fatality in extremely rare occasions. The diagnosis is made via lymph node biopsy and histopathology. Our patient was a young female who presented with shortness of breath, fever, and malaise. Physical examination revealed significant cervical and axillary lymphadenopathy. Chest X-ray displayed multilobar pneumonia. She required intubation and mechanical ventilation for progressive respiratory distress. Histopathology of lymph nodes demonstrated variable involvement of patchy areas of necrosis within the paracortex composed of karyorrhectic debris with abundant histiocytes consistent with KFD. After initial stabilization, the patient's condition quickly deteriorated with acute anemia, thrombocytopenia and elevated prothrombin time, partial prothrombin time, and D-dimer levels. Disseminated intravascular coagulopathy(DIC) ensued resulting in the patient's fatality. DIC in KFD is not well understood, but it is an important cause of mortality in patients with aggressive disease.

关键词： Kikuchi-Fujimoto disease Disseminated intravascular coagulopathy Histiocytic necrotizing lymphadenitis Lymphadenopathy Fatality

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