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1
Joffre, Corinne, Anne-Laure Dinel, Mathilde Chataigner, Véronique Pallet, and Sophie Layé. "n-3 Polyunsaturated Fatty Acids and Their Derivates Reduce Neuroinflammation during Aging." Nutrients 12, no. 3 (February 28, 2020): 647. http://dx.doi.org/10.3390/nu12030647.
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Aging is associated to cognitive decline, which can lead to loss of life quality, personal suffering, and ultimately neurodegenerative diseases. Neuroinflammation is one of the mechanisms explaining the loss of cognitive functions. Indeed, aging is associated to the activation of inflammatory signaling pathways, which can be targeted by specific nutrients with anti-inflammatory effects. Dietary n-3 polyunsaturated fatty acids (PUFAs) are particularly attractive as they are present in the brain, possess immunomodulatory properties, and are precursors of lipid derivates named specialized pro-resolving mediators (SPM). SPMs are crucially involved in the resolution of inflammation that is modified during aging, resulting in chronic inflammation. In this review, we first examine the effect of aging on neuroinflammation and then evaluate the potential beneficial effect of n-3 PUFA as precursors of bioactive derivates, particularly during aging, on the resolution of inflammation. Lastly, we highlight evidence supporting a role of n-3 PUFA during aging.
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Wang, Huijuan, Yan Zhu, Dongchao Xie, Haihua Zhang, Yahui Zhang, Peng Jin, and Qizhen Du. "The Effect of Microwave Radiation on the Green Color Loss of Green Tea Powder." Foods 11, no. 16 (August 22, 2022): 2540. http://dx.doi.org/10.3390/foods11162540.
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Microwave radiation is one of the main heating methods for food processing, especially affecting the color quality of colorful foods. This work presents the effect of microwave radiation on the green color loss of green tea powder (GTP) by the color description (L*, a*, b*, and Ha of green tea powder, L*:whiteness/darkness, a*: redness/greenness, and b*: yellowness/blueness; Ha derived from Hunter a and b could visually describe the color space) of the Hunter color system. First, the L*, a*, and b* were determined from the GTP samples treated with various microwave powers with the change of time to investigate the kinetic of color loss. Then, the L*, a*, and b*and temperature of GTP samples with serious thickness treated with constant microwave power (700 W) for a different time were determined to study the effect of sample thickness on the color loss. Finally, the chemicals that contributed to color change in the GTP samples treated with mild, moderate, and severe radiation were analyzed. The results showed that L*, |a*| (|a*|was the absolute value of a*), b*, and Ha decreased with the power increase in microwave radiation, and their changes conformed to the first-order kinetics. The activation energies (Ea) of different thickness GTP for change of L*, a*, b*, and Ha values could be predicted with the fitting models, and Ea for 20 mm-thick GTP were approximately 1/5, 1/8, 1/8, and 1/13 of those for 4 mm-thick GTP. The color loss was mainly caused by the Mg2+ loss of chlorophylls and the formation of derivates under mild radiation, the degradation of chlorophylls and the formation of theaflavin from catechins under moderate radiation, and the degradation of chlorophylls and their derivates accompanied by Maillard reaction between reducing sugar and amino acids under severe radiation. The results indicate that sample thickness and radiation time are two key parameters to keeping the color of GTP in food processing and microwave pasteurization.
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Yang, Xiu Li, Tie Min Zhang, and Sheng Wen. "Study on the Output Characteristics of Piezoelectricity Generator." Advanced Materials Research 156-157 (October 2010): 908–14. http://dx.doi.org/10.4028/www.scientific.net/amr.156-157.908.
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. For the purpose of improving the output power of piezoelectricity generator (PG), this paper derivates the improving equivalent circuit of piezoelectricity element according to piezoelectricity effect. The dielectric loss and conductive loss are considered. The dielectric loss is caused by the hysteretic effect between leakage current and electric intensity in the medium inside. The conductive loss is caused by the ceramic particles boundary conditions. The relationship between output voltage and current is set up. The relationship between resistance and output power is set up. The relationship between output voltage and out power is set up. Those relationships are simulated and experimented. From the results, it is can be known that there is an optimum load(200 ) for the maximum output power (70 ) in condition of fixed structure, size and fixed excitation frequency and amplitude. With the increasing of voltage, the current is decreasing with parabolic form and the output power increases lowly to a maximum power firstly, and then decreases fast.
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Miljkovic, Ljubomir. "THE ROLE OF FINANCIAL DERIVATIVES IN FINANCIAL RISKS MANAGEMENT." MEST Journal 11, no. 1 (January 15, 2023): 97–104. http://dx.doi.org/10.12709/mest.11.11.01.09.
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Financial derivatives are financial instruments whose price is derived from the basic financial instruments' prices. They represent derivative financial instruments created based on the existence of primary instruments, such as shares, bonds, stock market indices, or other forms of assets. It is precisely the benefit of using derivatives that point to their basic function. The primary function refers to risk protection and reduction of exposure to some instruments, markets, currencies, countries, regions, and others. In this case, we are talking about derivatives for hedging investments or currency positions. Those positions are taken on financial markets in specific instruments or currencies. Likewise, exposure to certain entities that issue financial instruments can be replaced or reduced to reasonable or prescribed measures by using derivatives. Derivatives offer a significant advantage: risks are transferred when they are used. Market and price risks of the underlying asset are contractually transferred to the financial derivative through the contract design. Of course, derivative financial instruments also have disadvantages. For example, there is a risk of total loss for some. The research subject in this paper is the role of financial derivatives, derived financial instruments, and their role in financial risk management. In this paper, the author emphasizes the basic types and characteristics of financial derivatives, their benefits, and the risks market participants may face if they use the derivates.
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Xiong, Jingjing, Shaoqi Yu, Daidai Wu, Xiaoshu Lü, Junhong Tang, Weihong Wu, and Zhitong Yao. "Pyrolysis treatment of nonmetal fraction of waste printed circuit boards: Focusing on the fate of bromine." Waste Management & Research: The Journal for a Sustainable Circular Economy 38, no. 11 (January 6, 2020): 1251–58. http://dx.doi.org/10.1177/0734242x19894621.
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Advanced thermal treatment of electronic waste offers advantages of volume reduction and energy recovery. In this work, the pyrolysis behaviour of nonmetallic fractions of waste printed circuit boards was studied. The fate of a bromine and thermal decomposition pathway of nonmetallic fractions of waste printed circuit boards were further probed. The thermogravimetric analysis showed that the temperatures of maximum mass loss were located at 319°C and 361°C, with mass loss of 29.6% and 50.6%, respectively. The Fourier transform infrared Spectroscopy analysis revealed that the spectra at temperatures of 300°C–400°C were complicated with larger absorbance intensity. The nonmetallic fractions of waste printed circuit boards decomposed drastically and more evolved products were detected in the temperature range of 600°C–1000°C. The gas chromatography–mass spectrometry analysis indicated that various brominated derivates were generated in addition to small molecules, such as CH4, H2O and CO. The release intensity of CH4 and H2O increased with temperature increasing and reached maximum at 600°C–800°C and 400°C–600°C. More bromoethane (C2H5Br) was formed as compared with HBr and methyl bromide (CH3Br). The release intensity of bromopropane (C3H7Br) and bromoacetone (C3H5BrO) were comparable, although smaller than that of bromopropene (C3H5Br). More dibromophenol (C6H4Br2O) was released than that of bromophenol (C6H5BrO) in the thermal treatment. During the thermal process, part of the ether bonds first ruptured forming bisphenol A, propyl alcohol and tetrabromobisphenol A. Then, the tetrabromobisphenol A decomposed into C6H5BrO and HBr, which further reacted with small molecules forming brominated derivates. It implied debromination of raw nonmetallic fractions of waste printed circuit boards or pyrolysis products should be applied for its environmentally sound treating.
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Mao, Shu-cai, Jin-qing Qu, and Kang-cheng Zheng. "Theoretical Study on Electronic Gain-and-loss Properties of TEMPO and Its Derivates in Charge/Discharge Processes." Chinese Journal of Chemical Physics 25, no. 2 (April 2012): 161–68. http://dx.doi.org/10.1088/1674-0068/25/02/161-168.
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Huang, Yaru, Jiefang Yang, Yunyang Chi, Chun Gong, Haikuan Yang, Fanxin Zeng, Fang Gao, Xiaoju Hua, and Zongde Wang. "Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis, Inhibitory Activity, and Mechanism." Molecules 27, no. 17 (August 29, 2022): 5558. http://dx.doi.org/10.3390/molecules27175558.
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We synthesized a series of quinazolinone derivates as tyrosinase inhibitors and evaluated their inhibition constants. We synthesized 2-(2,6-dimethylhepta-1,5-dien-1-yl)quinazolin-4(3H)-one (Q1) from the natural citral. The concentration, which led to 50% activity loss of Q1, was 103 ± 2 μM (IC50 = 103 ± 2 μM). Furthermore, we considered Q1 to be a mixed-type and reversible tyrosinase inhibitor, and determined the KI and KIS inhibition constants to be 117.07 μM and 423.63 μM, respectively. Our fluorescence experiment revealed that Q1 could interact with the substrates of tyrosine and L-DOPA in addition to tyrosinase. Molecular docking studies showed that the binding of Q1 to tyrosinase was driven by hydrogen bonding and hydrophobicity. Briefly, the current study confirmed a new tyrosinase inhibitor, which is expected to be developed into a novel pigmentation drug.
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Vanhala, Otso. "Verbal derived stems and semantics of prefixed verbs in the earliest Lithuanian texts." Lietuvių kalba 17 (December 30, 2022): 39–48. http://dx.doi.org/10.15388/lk.2022.3.
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This article discusses the deverbal verb derivation by the means of the prefixes in the Old Lithuanian language, basing on the corpus of about 110 primary verbs and their approximately 460 derivates attested in the Evangelijos bei epistolos (Gospels and Epistles, ViE) and the Catechism (ViC) of Baltramiejus Vilentas, with additional data from other Prussian Old Lithuanian sources up to the year 1600.
By comparing the derived verbs with their bases occurring in the Old Lithuanian texts, the co-occurring morphological and semantical changes were found out. Attention is brought on the together co-occurring morphological and semantical changes used in deriving telic verbs from their often atelic bases, e. g. the loss of infinitive formants -ė- and -o-, as in giedoti ‘to sing’→ pragysti ‘to start to sing, to start to crow’, or the ablaut change in šaukti ‘to shout’ → prašukti ‘to cry out, to exclaim’. The change in telicity can be used to classify the derived verbs into aktionsart classes (e. g. ingressive/momentaneous, delimitative). The telic ingressive/momentaneous derivatives also have the nasal infix or -st- formant in the present tense.
This article shows that the non-prefixed verbs with ingressive or momentaneous meaning of the type gysti occur extremely rarely in the oldest Lithuanian texts, and are better seen as later de-prefixed derivatives of the type pragysti, i.e. pragysti → gysti. Similarly, the derived type pragiedoti is rare in Old Lithuanian as the prefixation is usually accompanied by the shortening of the infinitive stems in the derivatives of this semantic class, leading to pragysti, although the type pragiedoti also occurs. This has led to the formal patterning of the derivatives and base verbs into two new models similar to that of degti → sudegti, the two new patterns showing only a simple prefixation: gysti → pragysti and giedoti → pragiedoti.
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PAVLOTSKY, I. P., and M. STRIANESE. "IRREVERSIBILITY IN CLASSICAL MECHANICS AS A CONSEQUENCE OF POINCARÉ GROUP." International Journal of Modern Physics B 10, no. 21 (September 30, 1996): 2675–85. http://dx.doi.org/10.1142/s0217979296001185.
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In the post-Galilean approximation of Poincaré Group (i.e. in the approximation in which the corrections of order O (c−2), c denoting the light velocity, to the Galilei group are taken in account) the Lagrangians are singular on a submanifold of the phase space. It is a local singularity, which differs from the ones considered by Dirac. The dynamical properties are essentially peculiar on the studied singular surfaces.1–4 In particular, on some submanifolds of the singular manifold the velocities are not determined uniquely: in each point of the submanifold we get the infinite set of components of velocity. It means the loss of the reversibility of the motion in a sense that transformation of the phase space, corresponding to Lagrangian, has not a property of a group. It is shown, that if the values of the derivates of the molecular potentials are large enough the irreversibility of motion takes place. As consequence we obtain the relaxation to the equilibrium. This property does not exist if the Lagrangian is invariant with respect to Galilei Group.
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Fuhrmann, GF, and KJ Netter. "A Hundred-Year Researching History on the Low Ionic Strength in Red Blood Cells: Literature Review." Journal of Biomedical Research & Environmental Sciences 2, no. 3 (March 11, 2021): 139–68. http://dx.doi.org/10.37871/jbres1204.
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This review article provides a critical survey of work from 1904 to 2003 on the effects of low ionic strength in Red Blood Cells (RBCs) incubated in media with impermeable sugars such as sucrose. In 1904 Gürber A washed RBCs of different species with isotonic sucrose solution to eliminate the outside ions in order to better analyse their intracellular ionic composition; however, this approach was not feasible because of a substantial salt efflux from the cells. A prominent feature of the salt loss is the shrinking of the RBCs. A central role in the understanding of the ionic movements is thereby the new Donnan equilibrium of the anions. Experimental evidence has been given by Jacobs MH and Parpart AK in 1933. In the sucrose medium two phases could be predicted: 1) a very rapid anionic shift resulting in an unequal distribution of chloride and hydroxyl anions on both sides of the membrane and 2) a leakage of salts from the RBCs. In 1940 Wilbrandt W assumed that a positive membrane potential is in line with the salt loss at low ionic strength in RBCs. In 1977 Knauf PA, Fuhrmann GF, Rothstein S and Rothstein A observed in RBCs an inhibition of both, anion exchange and also of net anion efflux, by incubation with disulfonic stilbene derivates. At low ionic strength the Donnan equilibrium is immediately obtained by the Anion Exchanger Protein (AEP). The resulting positive membrane potential opens at least two new types of cation pores or channels. Thereby is the conductivity pathway for the anions, namely the AEP, in charge of the net anion loss at low ionic strength. The AEP pathway is extensively blocked by disulfonic stilbene compounds. The permeability ways for cations through these pores or channels are not yet explored.
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Santin, Marco, Stefano Brizzolara, Antonella Castagna, Annamaria Ranieri, and Pietro Tonutti. "Short-Term CO2 Treatment of Harvested Grapes (Vitis vinifera L., cv. Trebbiano) before Partial Dehydration Affects Berry Secondary Metabolism and the Aromatic Profile of the Resulting Wine." Plants 11, no. 15 (July 29, 2022): 1973. http://dx.doi.org/10.3390/plants11151973.
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High CO2 concentrations applied to harvested horticultural products can modify primary and secondary metabolism. This work reports the metabolic responses to short-term CO2 treatments of white-skinned grapes (cv Trebbiano) undergoing postharvest partial dehydration. The influence of CO2 treatments on the aroma profile of the derived sweet wine was also assessed. Harvested grapes were treated with gaseous CO2 (30%) or air (control) for 24 h and then dehydrated (about 45% of weight loss) before vinification. Lipophilic and phenolic compounds of grape skin and the wine aroma profile were analyzed. In CO2-treated berries, the lipophilic and phenolic compounds decreased at a reduced and faster rate, respectively, during dehydration. Aroma profile of wine from CO2-treated grapes showed a slight but significantly higher content of glycosylated C13 and terpene compounds, and a decrease/absence of free acids, vanillin derivates and other phenol volatiles. The higher content of volatile alcohols in wine from treated berries suggests that the alcoholic fermentation was triggered. CO2 application before the withering process of Trebbiano grapes affects the aroma profile of the resulting wine by altering the free:glycosylated volatiles ratio. This study provides information on the possible use of CO2 as metabolic elicitor to modulate the aroma profile of the resulting wines obtained after grape dehydration.
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Frnda, Jaroslav, Jan Nedoma, Radek Martinek, and Michael Fridrich. "Predicting Perceptual Quality in Internet Television Based on Unsupervised Learning." Symmetry 12, no. 9 (September 17, 2020): 1535. http://dx.doi.org/10.3390/sym12091535.
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Quality of service (QoS) and quality of experience (QoE) are two major concepts for the quality evaluation of video services. QoS analyzes the technical performance of a network transmission chain (e.g., utilization or packet loss rate). On the other hand, subjective evaluation (QoE) relies on the observer’s opinion, so it cannot provide output in a form of score immediately (extensive time requirements). Although several well-known methods for objective evaluation exist (trying to adopt psychological principles of the human visual system via mathematical models), each of them has its own rating scale without an existing symmetric conversion to a standardized subjective output like MOS (mean opinion score), typically represented by a five-point rating scale. This makes it difficult for network operators to recognize when they have to apply resource reservation control mechanisms. For this reason, we propose an application (classifier) that derivates the subjective end-user quality perception based on a score of objective assessment and selected parameters of each video sequence. Our model integrates the unique benefits of unsupervised learning and clustering techniques such as overfitting avoidance or small dataset requirements. In fact, most of the published papers are based on regression models or supervised clustering. In this article, we also investigate the possibility of a graphical SOM (self-organizing map) representation called a U-matrix as a feature selection method.
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Sorokin, Danila, Yuri Shchegolev, Alexander Scherbakov, Oxana Ryabaya, Margarita Gudkova, Lev Berstein, and Mikhail Krasil’nikov. "Metformin Restores the Drug Sensitivity of MCF-7 Cells Resistant Derivates via the Cooperative Modulation of Growth and Apoptotic-Related Pathways." Pharmaceuticals 13, no. 9 (August 21, 2020): 206. http://dx.doi.org/10.3390/ph13090206.
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The phenomenon of the primary or acquired resistance of cancer cells to antitumor drugs is among the key problems of oncology. For breast cancer, the phenomenon of the resistance to hormonal or target therapy may be based on the numerous mechanisms including the loss or mutation of estrogen receptor, alterations of antiapoptotic pathways, overexpression of growth-related signaling proteins, etc. The perspective approaches for overcoming the resistance may be based on the usage of compounds such as inhibitors of the cell energetic metabolism. Among the latter, the antidiabetic drug metformin exerts antitumor activity via the activation of AMPK and the subsequent inhibition of mTOR signaling. The experiments were performed on the ERα-positive MCF-7 breast cancer cells, the MCF-7 sublines resistant to tamoxifen (MCF-7/T) and rapamycin (MCF-7/Rap), and on triple-negative MDA-MB-231 breast cancer cells. We have demonstrated metformin’s ability to enhance the cytostatic activity of the tamoxifen and rapamycin on both parent MCF-7 cells and MCF-7-resistant derivates mediated via the suppression of mTOR signaling and growth-related transcriptional factors. The cooperative effect of metformin and tested drugs was realized in an estrogen-independent manner, and, in the case of tamoxifen, was associated with the activation of apoptotic cell death. Similarly, the stimulation of apoptosis under metformin/tamoxifen co-treatment was shown to occur in the MCF-7 cells after steroid depletion as well as in the ERα-negative MDA-MB-231 cells. We conclude that metformin co-treatment may be used for the increase and partial restoration of the cancer cell sensitivity to hormonal and target drugs. Moreover, the combination of metformin with tamoxifen induces the apoptotic death in the ERα-negative breast cancer cells opening the additional perspectives in the treatment of estrogen-independent breast tumors.
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Calis, Zehra, Rasim Mogulkoc, and Abdülkerim Kasim Baltaci. "The Roles of Flavonols/Flavonoids in Neurodegeneration and Neuroinflammation." Mini-Reviews in Medicinal Chemistry 20, no. 15 (October 16, 2020): 1475–88. http://dx.doi.org/10.2174/1389557519666190617150051.
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The inflammatory process in the human body is a physiological response involving many cellular types and mediators. It results in scar formation to separate the damaged area from the surrounding healthy tissue. Because of increased blood-brain barrier permeability following inflammation, leukocytes infiltrate the CNS and are also supplemented by proinflammatory mediators. However, an acute inflammatory process after cerebral trauma or stroke may also result in a prolonged lesion formation, leading to a severe neuronal loss. The prolonged inflammatory process in the CNS may cause serious damage to the neuronal system. It may lead to CNS damage in such a way that endangers functional integration and proinflammatory system balance. Effects of different flavonoid species on ischemia-reperfusion injury and cognition and function have also been shown in experimental studies. Flavonoids are presented broadly in plants and diets. They are believed to have various bioactive effects including anti-viral, anti-inflammatory, cardioprotective, anti-diabetic, anti-cancer, anti-aging, etc. Quercetine is the predominant dietary flavonoid. Main sources are tea, onion, and apple. It is demonstrated that the frequently consumed food like soybean, peanut, mustard, rice, sesame, olive, potatoes, onion, and oats contain flavonoids. Catechin and its derivates which are isolated from tea leaves have antioxidant activity but in low doses, their prooxidant effects are also reported. Ipriflavone which is a synthetic flavonoid may increase total calcium in bone. In this review, the effects of flavonoids species on the inflammatory process in the neurodegenerative process were examined as general.
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Kumps, Camille, Belinda Campos-Xavier, Yvonne Hilhorst-Hofstee, Carlo Marcelis, Marius Kraenzlin, Nicole Fleischer, Sheila Unger, and Andrea Superti-Furga. "The Connective Tissue Disorder Associated with Recessive Variants in the SLC39A13 Zinc Transporter Gene (Spondylo-Dysplastic Ehlers–Danlos Syndrome Type 3): Insights from Four Novel Patients and Follow-Up on Two Original Cases." Genes 11, no. 4 (April 14, 2020): 420. http://dx.doi.org/10.3390/genes11040420.
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Recessive loss-of-function variants in SLC39A13, a putative zinc transporter gene, were first associated with a connective tissue disorder that is now called “Ehlers–Danlos syndrome, spondylodysplastic form type 3” (SCD-EDS, OMIM 612350) in 2008. Nine individuals have been described. We describe here four additional affected individuals from three consanguineous families and the follow up of two of the original cases. In our series, cardinal findings included thin and finely wrinkled skin of the hands and feet, characteristic facial features with downslanting palpebral fissures, mild hypertelorism, prominent eyes with a paucity of periorbital fat, blueish sclerae, microdontia, or oligodontia, and—in contrast to most types of Ehlers–Danlos syndrome—significant short stature of childhood onset. Mild radiographic changes were observed, among which platyspondyly is a useful diagnostic feature. Two of our patients developed severe keratoconus, and two suffered from cerebrovascular accidents in their twenties, suggesting that there may be a vascular component to this condition. All patients tested had a significantly reduced ratio of the two collagen-derived crosslink derivates, pyridinoline-to-deoxypyridinoline, in urine, suggesting that this simple test is diagnostically useful. Additionally, analysis of the facial features of affected individuals by DeepGestalt technology confirmed their specificity and may be sufficient to suggest the diagnosis directly. Given that the clinical presentation in childhood consists mainly of short stature and characteristic facial features, the differential diagnosis is not necessarily that of a connective tissue disorder and therefore, we propose that SLC39A13 is included in gene panels designed to address dysmorphism and short stature. This approach may result in more efficient diagnosis.
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Djordjevic, Aleksandar, Ivana Icevic, and Visnja Bogdanovic. "Complex with fullerenol and copper (II)." Chemical Industry 63, no. 3 (2009): 171–75. http://dx.doi.org/10.2298/hemind0903171d.
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Polyhydroxy fulleren derivates have significant potential in nanomedical application. Research of polyanion nanoparticle fullerenol C60(OH)24 is of high significance for interpretation of biological mechanisms. This paper investigated the properties of polyanion nanoparticle fullerenol C60(OH)24 as a potential polydentat ligand. Fullerenol C60(OH)24 water solutions were added in solution of [Cu(NH3)4]2+ in order to form a dark brown complex. Absorbance of [Cu(NH3)4]2+ solution was decreasing with increasing concentration of polyanion nanoparticle nanoligand fullerenol. This relation was determined in all investigated concentrations of [Cu(NH3)4]2+. The ratio of Cu2+ complex composer to polyanion polydentat nanoligand fullerenol had an increase from 1.5 to 9, proportional to the increase of the complex composer concentration and decrease of polyanion polydentat nanoligand fullerenol in the alkali medium. The thermogram TGA-DTA of fullerenol and fullerenol and CuSO4 complex, clearly show endothermic effects (which are the result of dehydratation and dehydroxylation) and exothermic effects (as the result of degradation of C60(OH)24 molecules and processes of oxidation in CO, CO2. At the beginning of TGA-DTA fullerenol thermogram, there is a very well defined endothermic peak of water loss at 100?C, followed by mass decrease as a consequence of lost hydroxyl groups, covalent bounded for C60. The influence of the complex composer is manifested in the moving of thermal stability towards lower temperatures. The complex composer is a catalyst of the process of polyanion polydentat nanoligand fullerenol oxidation to CO and CO2. The temperature peak of fullerenol oxidation is at 490?C and in the case of complex oxidation two peaks were detected at 380 and 410?C.
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Wang, Lei, Xuguo Duan, and Jing Wu. "Enhancing the α-Cyclodextrin Specificity of Cyclodextrin Glycosyltransferase from Paenibacillus macerans by Mutagenesis Masking Subsite −7." Applied and Environmental Microbiology 82, no. 8 (February 5, 2016): 2247–55. http://dx.doi.org/10.1128/aem.03535-15.
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ABSTRACTCyclodextrin glycosyltransferases (CGTases) (EC 2.4.1.19) catalyze the conversion of starch or starch derivates into mixtures of α-, β-, and γ-cyclodextrins. Because time-consuming and expensive purification procedures hinder the widespread application of single-ingredient cyclodextrins, enzymes with enhanced specificity are needed. In this study, we tested the hypothesis that the α-cyclodextrin selectivity ofPaenibacillus maceransα-CGTase could be augmented by masking subsite −7 of the active site, blocking the formation of larger cyclodextrins, particularly β-cyclodextrin. Five single mutants and three double mutants designed to remove hydrogen-bonding interactions between the enzyme and substrate at subsite −7 were constructed and characterized in detail. Although the rates of α-cyclodextrin formation varied only modestly, the rate of β-cyclodextrin formation decreased dramatically in these mutants. The increase in α-cyclodextrin selectivity was directly proportional to the increase in the ratio of theirkcatvalues for α- and β-cyclodextrin formation. The R146A/D147P and R146P/D147A double mutants exhibited ratios of α-cyclodextrin to total cyclodextrin production of 75.1% and 76.1%, approximately one-fifth greater than that of the wild-type enzyme (63.2%), without loss of thermostability. Thus, these double mutants may be more suitable for the industrial production of α-cyclodextrin than the wild-type enzyme. The production of β-cyclodextrin by these mutants was almost identical to their production of γ-cyclodextrin, which was unaffected by the mutations in subsite −7, suggesting that subsite −7 was effectively blocked by these mutations. Further increases in α-cyclodextrin selectivity will require identification of the mechanism or mechanisms by which these small quantities of larger cyclodextrins are formed.
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Schott, Matthias, Cornelia Sagert, Holger S. Willenberg, Sven Schinner, Uwe Ramp, Andrea Varro, Andreas Raffel, et al. "Carcinogenic Hypergastrinemia: Signet-Ring Cell Carcinoma in a Patient with Multiple Endocrine Neoplasia Type 1 with Zollinger-Ellison’s Syndrome." Journal of Clinical Endocrinology & Metabolism 92, no. 9 (September 1, 2007): 3378–82. http://dx.doi.org/10.1210/jc.2007-0283.
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Abstract Context: Gastric neuroendocrine tumors are rare neoplasms that originate from gastric enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin and its derivates have been reported to regulate epithelial cell proliferation, migration, and differentiation. Mutations in the epithelial cadherin (E-cadherin) gene have been shown to be associated with the occurrence of diffuse gastric carcinomas in affected families. Objective: In this study we investigated the histopathological and molecular findings in the gastrointestinal wall of a patient with multiple endocrine neoplasia type 1 with malignant duodenal gastrinoma and multiple gastric ECL cell tumors, who additionally developed a signet-ring cell carcinoma of the stomach. Design and Patient: Biopsies from the gastrointestinal tract of a patient with multiple endocrine neoplasia type 1 were immunostained for vesicular monoamine transporter-2 and E-cadherin. Nonamidated gastrin products were measured in the serum of the patient using antibodies that react with progastrin, Gly-extended, and amidated gastrins. Genetic analyses were performed to exclude germ-line mutations within the E-cadherin gene. Results: Immunohistochemical studies of gastric ECL cell tumors showed a largely diminished E-cadherin expression in comparison to gastric surface mucosa cells and a loss of E-cadherin expression in the cells of the signet-ring carcinoma. Detailed biochemical measurements revealed progastrin concentrations that were approximately 20%, and Gly-gastrin concentrations that were approximately 10% the amidated gastrin concentrations in plasma. Molecular analyses revealed no E-cadherin germ-line mutation. Conclusion: Our immunohistochemical studies might suggest that the gastrinoma-associated excessive progastrin tissue concentrations led to diminished expression of E-cadherin within the gastric mucosa and promoted tumor development of a signet-ring cell carcinoma.
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Lorusso, D., S. Pignata, G. Scambia, V. Zagonel, N. Riva, A. Febbraro, C. Pisano, S. Greggi, E. Breda, and A. Morabito. "A multicentre phase 2 study of carboplatin (C) plus pegylated liposomal doxorubicin (PLD) as first-line chemotherapy for patients (pts) with advanced or recurrent endometrial carcinoma (AEC): The END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer) Group." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 5041. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.5041.
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5041 Background: Anthracyclines and platinum derivates are active drugs for pts with AEC, but new schedules with higher efficacy and better tolerability are needed. A prospective phase 2 study was conducted to describe tolerability and activity of C + PLD in pts with AEC. Methods: Pts with chemo-naïve AEC, PS ≤2, aged less than 75 years and with at least one measurable lesion were eligible. Treatment was C (AUC 5) + PLD (40 mg/m2) on day 1 every 4 weeks, up to 6 cycles. A single-stage design was applied. With objective response as primary endpoint, type I error = 0.05 and II error = 0.10, p0 = 0.20, p1= 0.40, 42 patients were needed, with at least 13 objective responses to define the treatment active. Response was assessed by RECIST and toxicity was coded with NCI-CTC. Results: From November 2002 to July 2005, 42 pts were enrolled at 5 Institutions. Median age was 64 years (31–74). PS was 0/1/2 in 28/13/1 pts, respectively. 62% of pts were stage IV. Out of 40 pts out of treatment, 3 complete (7.5%) and 20 partial responses (50%) have been already observed, for an overall response rate of 57.5% (95% exact CI: 40.9–73.0). One death potentially related to treatment was recorded (death at home for unknown reasons after 6th cycle). Other relevant toxicities (% of pts) were g3/4 neutropenia 30%/15%, febrile neutropenia 5%, g3/4 thrombocytopenia pts 17.5%/5%, g3/4 anemia 32.5%/5%, g3 heart rhythm 1 pt, g2 liver toxicity 1pt. Skin toxicity was mild: g1 12.5%, g2 7.5%, g3 5%. Hair loss: complete 1 pt, partial 12.5%. Conclusions: The combination of C and PLD shows a good activity and a favourable toxicity profile in first-line chemotherapy of pts with AEC, deserving further studies in this setting. No significant financial relationships to disclose.
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Diepstraten, Franciscus A., Annelot JM Meijer, Martine van Grotel, Sabine LA Plasschaert, Alexander E. Hoetink, Marta Fiocco, Geert O. Janssens, Robert J. Stokroos, and Marry M. van den Heuvel-Eibrink. "A Study on Prevalence and Determinants of Ototoxicity During Treatment of Childhood Cancer (SOUND): Protocol for a Prospective Study." JMIR Research Protocols 11, no. 4 (April 7, 2022): e34297. http://dx.doi.org/10.2196/34297.
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Background Some children with central nervous system (CNS) and solid tumors are at risk to develop ototoxicity during treatment. Up to now, several risk factors have been identified that may contribute to ototoxicity, such as platinum derivates, cranial irradiation, and brain surgery. Comedication, like antibiotics and diuretics, is known to enhance ototoxicity, but their independent influence has not been investigated in childhood cancer patients. Recommendations for hearing loss screening are missing or vary highly across treatment protocols. Additionally, adherence to existing screening guidelines is not always optimal. Currently, knowledge is lacking on the prevalence of ototoxicity. Objective The aim of the Study on Prevalence and Determinants of Ototoxicity During Treatment of Childhood Cancer (SOUND) is to determine the feasibility of audiological testing and to determine the prevalence and determinants of ototoxicity during treatment for childhood cancer in a national cohort of patients with solid and CNS tumors. Methods The SOUND study is a prospective cohort study in the national childhood cancer center in the Netherlands. The study aims to include all children aged 0 to 19 years with a newly diagnosed CNS or solid tumor. Part of these patients will get audiological examination as part of their standard of care (stratum 1). Patients in which audiological examination is not the standard of care will be invited for inclusion in stratum 2. Age-dependent audiological assessments will be pursued before the start of treatment and within 3 months after the end of treatment. Apart from hearing loss, we will investigate the feasibility to screen patients for tinnitus and vertigo prevalence after cancer treatment. This study will also determine the independent contribution of antibiotics and diuretics on ototoxicity. Results This study was approved by the Medical Research Ethics Committee Utrecht (Identifier 20-417/M). Currently, we are in the process of recruitment for this study. Conclusions The SOUND study will raise awareness about the presence of ototoxicity during the treatment of children with CNS or solid tumors. It will give insight into the prevalence and independent clinical and cotreatment-related determinants of ototoxicity. This is important for the identification of future high-risk patients. Thereby, the study will provide a basis for the selection of patients who will benefit from innovative otoprotective intervention trials during childhood cancer treatment that are currently being prepared. Trial Registration Netherlands Trial Register NL8881; https://www.trialregister.nl/trial/8881 International Registered Report Identifier (IRRID) DERR1-10.2196/34297
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Levartovsky, A., I. Cohen, C. M. Abitbol, M. Yavzori, E. Fudim, O. Picard, U. Kopylov, S. Ben-Horin, and B. Ungar. "P484 Do vedolizumab trough levels predict response to consecutive therapy in Inflammatory Bowel Disease?" Journal of Crohn's and Colitis 16, Supplement_1 (January 1, 2022): i451. http://dx.doi.org/10.1093/ecco-jcc/jjab232.611.
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Abstract Background Vedolizumab trough serum levels have been associated with clinical and endoscopic response in patients with inflammatory bowel disease (IBD), albeit findings have not been conclusive. A recent study demonstrated that higher trough vedolizumab levels before therapy escalation predict optimal outcome. Our aim was to identify whether vedolizumab trough levels predict outcome of consecutive biologic or immunomodulatory therapy. Methods This retrospective study included IBD patients consecutively receiving vedolizumab therapy between November 2014 and June 2021 at Sheba Medical Center. Only patients who lost response to vedolizumab therapy, and had available trough levels prior to therapy cessation were included. Clinical and endoscopic scores, as well as drug retention, were recorded at 6 and 12 months post switching therapy. Results Overall, 66 IBD patients (36 CD, 30 UC) who lost response to vedolizumab therapy were included. They were treated with vedolizumab for a median of 47 weeks (IQR 31–85). Seventy-two percent of patients (48/66) were priorly treated with anti-TNF therapy (infliximab or adalimumab). After vedolizumab cessation, 66.7% of patients were switched to biologic therapy. These included 25.8% (17/66) to ustekinumab, 22.7% (15/66) to infliximab, 7.6% (5/66) to adalimumab, 6.1% (4/66) to certolizumab and 4.5% (3/66) to golimumab. The remaining 33.3% of patients switched to tofacitinib (10.6%), 5-ASA derivates or immunomodulator monotherapy (12.1%) or to a study therapy protocol (10.6%). Median vedolizumab trough levels at therapy cessation were 32.25 μg/ml (IQR 12.8–61.4). Trough drug levels at therapy cessation were not associated with retention of biological or immunomodulatory therapy at 6 months [median 29.1 μg/ml (IQR 12.4–57.6) vs 33.8 μg/ml (IQR 27.9–58), p = 0.43] and at 12 months [median, 38.2 μg/ml (IQR 14.5–76.3) vs 30.1 μg/ml (IQR 11.5–45), p = 0.57] for patients who retained consecutive therapy versus those who did not. Conclusion Vedolizumab trough serum levels before therapy cessation due to loss of response do not predict retention of consecutive therapy.
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Herberhold, Max, Guo-Xin Jin, and Arnold L. Rheingold. "Sulfurization and Selenization of the Halfsandwich Nitrosylmetal Complexes Cp*M(CO)2NO (M = Cr, Mo) and Cp*M(NO)I2 (M = Mo, W)." Zeitschrift für Naturforschung B 48, no. 11 (November 1, 1993): 1488–98. http://dx.doi.org/10.1515/znb-1993-1106.
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The photo-induced decarbonylation of Cp*Cr(CO)2NO in acetonitrile solution in the presence of excess sulfur leads to the cyclo-pentasulfido complex Cp*Cr(NO)(S5) (1 a), while in the case of limited sulfur supply the binuclear bis(µ-disulfido) complex Cp*2Cr2(NO)2(µ-S2)2 (4a) is formed preferentially. The corresponding reaction with elemental selenium produces Cp*2Cr2(NO)2(µ-Se2)2 (4b), irrespective of the available amount of selenium. Photodecarbonylation of Cp*Mo(CO)2NO gives only the binuclear derivates Cp*2Mo2(NO)2(µ-E2) (E = S (5a), Se (5b)) which are also obtained by treating Cp*Mo(NO)I2 with H2S or H2Se, respectively. Nitrosyl loss predominates if the tungsten complex Cp*W(NO)I2 is reacted with H2S; in an argon atmosphere the products are Cp*W(S)(S2)(I) (7a) and Cp*2W2(S)2(µ-S)2 (8a), while in air some Cp*W(NO)(S5) (3a) and the oxo compounds Cp*W(O)(S2)I (7c), Cp*2W2(O)2(µ-S)2 (8c) and Cp*2W2(S)(O)(µ-S)2 (8d) are formed. The analogous reaction with H2Se leads to Cp*W(NO)(Se5) (3b), Cp*2W2(O)2(µ-Se)2 (9c) and Cp*2W2(Se)(O)(µ-Se)2 (9d), respectively. The binuclear tungsten complexes 8a,c,d and 9c,d contain a central W(µ-E)2W framework (E = S or Se) which is unaffected by air, while terminal sulfido and selenido ligands are quantitatively converted into the corresponding terminal oxo ligands in the presence of air in CH2C12 or THF solution. With the preparation of Cp*2W2(O)2(µ-E)2 (E = S (8c) and Se (9c)), the series of dioxo complexes containing a pair of monochalcogen bridges (E = O, S, Se, Te) has become complete.The new complexes have been characterized by their IR (v(NO)), 1H and 13C NMR (Cp*) spectra as well as by electron-impact mass spectrometry. According to the X-ray structure analyses, the binuclear compounds Cp*2Cr2(NO)2(µ-S2)2 (4a) and Cp*2Mo2(NO)2(µ-Se2)2 (5b) contain two 14-electron [Cp*M(NO)2] fragments which are connected by a pair of dichalcogen (η1,η2-E2) bridging ligands (M = Cr or Mo, E = S or Se). The central M2E2 four-membered ring is not planar, and the binuclear molecules are chiral.
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Ruiz-Gutiérrez, V., and R. Maestro Durán. "Incorporación de los derivados grasos de anilina en los quilomicrones linfáticos." Grasas y Aceites 43, no. 2 (April 30, 1992): 61–65. http://dx.doi.org/10.3989/gya.1992.v43.i2.1175.
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Corinaldesi, Giorgio, and Christian Corinaldesi. "Management and Strategy of Thromboprophylaxis for Venous Thromboembolism in Pregnancy." Blood 110, no. 11 (November 16, 2007): 3996. http://dx.doi.org/10.1182/blood.v110.11.3996.3996.
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Abstract Venous thromboembolism (VTE) in pregnancy increases the risk of foetal loss, foetal growth retardation, pre-eclampsia, and placental abruption; VTE was more frequent and the risk was higher in ante partum RR 2.5, 95% CI 1.2–5.2. range 2.1%–4.2%, and post partum RR 2.9, 95% CI 1.4–6.9. range 7.1%–11.5%. Risk factors for VTE during pregnancy are: age >38 years, obesity, familial or personal history of VTE, abnormalities of blood flow, and vessel wall injury; they lead to venous thrombosis just as comorbility conditions associated to thrombophilia or to a state of hypercoagulability (Factor V Leiden, prothrombin gene mutation G20210A, hyperhomocysteinemia with C677T mutation, deficiencies of PS and/or PC, ATIII, elevated levels of FVIII, dysfibrinogenemia, anticardiolipin antibodies / lupus anticoagulant), or they may be associated to additional risk factors (sepsis, inflammation, recent major surgery, prolonged bed rest, trauma, severe varicose vein); any of these factors approximately tripled the absolute risk of VTE. Antithrombotic agents during pregnancy in patients with a familial history of thrombosis are recommended prior and during pregnancy. The overall prevalence of VTE in these patients is 60% without any therapy; in about 80% of these cases there was an involvement of the left lower limb; the high risk for pulmonary embolism (60% in patients with Factor V Leiden deficiency) justifies the thrombo-prophylaxis throughout pregnancy and puerperium. The complications of pregnancy associated with maternal carriage of Factor V Leiden are: VTE, hypertensive disorder (gestational hypertension, HELLP-syndrome, preeclampsia), late pregnancy loss, intrauterine growth restriction, placental abruption. We have studied a 28 years old patient that showed leg pain, skin tension, swelling, oedema, fever, tenderness, low abdominal pain, and raised WBC, with Factor V Leiden (R506Q) heterozygosis and a familial history and personal history of recurrent VTE. Factor V Leiden is resistant to the action of activated C-protein (ACP) because the mutation G1691A (substitution of a glutamine for arginine residue 506) occurs on ACP cleavage site (there are three major cleavage site for this molecule: R 306, R 506, R 679); the frequency of Factor V Leiden in Caucasian people was between 3–10% (7.2% heterozygotes - 0.8% homozygotes). An exhaustive bilateral comparative color-Doppler ultrasound investigation was performed during and after the end of pregnancy for six months. Current strategy to prevent thrombus formation consists on using unfractioned heparin (UHF), low molecular weight heparin (LMWH) (enoxaparine 40 mg sc daily, or 30 mg sc twice daily; or dalteparin 5000 U s.c. once or twice daily), or consists on danaparoid that do not cross the placenta; heparin may be associated with warfarin, and this regimen can be continued in the post partum for 12 weeks. We used active prophylaxis with enoxaparine 40 mg sc daily with ASA 150 mg during the second and third three months, (plasma heparin levels measured as anti FX activity of 0.2 to 0.6 U/ml), in addition to graduated compression socks; medications used during pregnancy included folic acid and iron supplement (80 mg/daily) without any bleeding event or other clinic problem. The therapeutic approach to VTE includes two potential foetal complication: teratogenesis from coumarin derivates (nasal hypoplasia, stippled epiphyses, optic atrophy, cleft lip), and bleeding; the main maternal complications include bleeding, osteoporosis, heparin induced thrombocytopenia which may occur during both therapy with heparin or LMWH.
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Marusyk, Andriy. "Abstract IA016: Resistance to ALK-targeting therapies in lung cancers is acquired through complex, context specific evolutionary trajectories." Cancer Research 82, no. 10_Supplement (May 15, 2022): IA016. http://dx.doi.org/10.1158/1538-7445.evodyn22-ia016.
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Abstract Background. Despite remarkable initial efficacy, targeted therapies eventually fail in advanced lung cancers. This failure reflects the ability of neoplastic populations to adapt to therapy-imposed selection pressures. In principle, disrupting this ability might transform clinical outcomes. However, contrast to the detailed understanding of individual molecular mechanisms of resistance, our knowledge of how neoplastic populations adapt remains limited. Based on inferences from mechanistic studies, it is commonly assumed that adaptation results from the acquisition of a single mutational change, or an epigenetic switch-like phenotypic state transition. Findings. Using a combination of experimental studies and in silico modeling, we sought to dissect evolutionary trajectories towards acquired resistance to clinically relevant ALK inhibitors in experimental models of ALK+ NSCLC. Consistent with the growing appreciation of the phenomenon of therapy persistence, we found that near-complete resistance originates from weakly resistant populations. Surprisingly, these populations were phenotypically heterogeneous and differed between different ALKi. Rather than the frequently assumed saltational transition from persistence to resistance, we observed a gradual loss of therapy sensitivity, mediated by acquisition of multiple epigenetic and mutational resistance mechanisms. This multifactorial progression was observed even in the presence of mutational drivers that are ostensibly sufficient to explain clinical resistance. Interestingly, even though resistance to any of the ALKi was linked with cross-resistance to other ALKi, we observed a clear divergence of evolutionary trajectories under selection with distinct inhibitors. In contrast, independent resistant derivates selected with same inhibitor displayed remarkable convergence, where similar phenotypic states were achieved through distinct mechanistic changes. Notably, evolving cells displayed inhibitor-specific, temporally restricted collateral sensitivities, suggesting new opportunities for therapeutic interference. Whereas, in vitro, evolving resistance was primarily shaped by cell-intrinsic mechanisms, acquisition of resistance in vivo reflected an interplay between cell-intrinsic mechanisms and stromal sheltering niches. Conclusions. Therapy resistance can be acquired through complex, context and inhibitor specific evolutionary trajectories that integrate mutational and epigenetic changes as well as modifying effect of macro and micro-environments. Consequently, even in the presence of strong mutational drivers, focusing on a single resistance mechanism at a time is unlikely to produce substantial therapeutic breakthroughs. Our results suggest a need for multifactorial therapeutic interventions that disrupt the ability of tumors to adapt to therapies. Citation Format: Andriy Marusyk. Resistance to ALK-targeting therapies in lung cancers is acquired through complex, context specific evolutionary trajectories [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA016.
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Chinni, Gregorio. "Germ hypoellipticity and loss of derivatives." Proceedings of the American Mathematical Society 140, no. 7 (July 1, 2012): 2417–27. http://dx.doi.org/10.1090/s0002-9939-2011-11252-8.
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Leoni, Patrick L. "Stop-loss strategies and derivatives portfolios." International Journal of Business Forecasting and Marketing Intelligence 1, no. 1 (2008): 82. http://dx.doi.org/10.1504/ijbfmi.2008.020816.
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Dalix, E., M. Maalouf, S. Peyroche, A. Vanden-Bossche, C. A. Arthaud, S. Hodin, H. Marotte, and R. Müller. "POS0695 EFFECT OF METHOTREXATE AND FOLIC ACID CO-ADMINISTRATION IN ARTHRITIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 627.1–627. http://dx.doi.org/10.1136/annrheumdis-2022-eular.3150.
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BackgroundMethotrexate (MTX) is the recommended first-line treatment for rheumatoid arthritis. Adjuvant-induced arthritis (AIA) rat is a robust model with a high prevalence of arthritis used to investigate arthritis. MTX reduces inflammation, but associated with adverse events, such as gastrointestinal, hepatic, and hematology toxicity (1). To reduce these side effects, folic acid (FA) is administrated at distance to MTX with no defined recommendation for its dosing (5-25mg/week) or time point of administration (2) (1-3 days after MTX application). Whether the complicated therapeutic regimen with MTX once a week and FA at another time point affects compliance is an open question. MTX is metabolized in polyglutamates derivates (MTX-PG), which is a biomarker of MTX efficacy as its half-life (1-4 weeks) is longer than MTX (4h) (3).ObjectivesThe aim of this study was to assess efficacy and tolerance of co-administration of MTX and FA compared to MTX with FA applied one day after MTX in the AIA.MethodsFemale Lewis rat were randomly divided in three groups and received an injection of Mycobacterium butyricum defining day (D) 0 to induce arthritis. An historic AIA group was used as control. Treatment began on D9, one day before arthritis onset in this model. The first group rats were treated with MTX only (n=13), the second group received MTX and FA at the same day (n=14), and the third group received FA one day after MTX administration (n=14). MTX was administrated intraperitoneally (IP) at 1 mg/kg every 3 days (4) and FA was delivered IP at 0.17 mg/kg. Arthritic index (AI) and ankle circumference (AC) were monitored to assess arthritis. Microcomputed tomography of the ankle was performed to assess bone loss. Moreover, complete blood count, transaminases, and MTX-PG were assessed.ResultsArthritis developed at D10 in all groups. AI and AC were similar in MTX groups at the various time points. At D17, arthritis severity was lower in MTX groups (AI (mean and standard deviation): 1.4 ± 1.6; AC: 35 ± 7 mm) compared to AIA historical group (AI: 3.3 ± 0.6; AC: 42 ± 4 mm). Bone erosion and bone loss parameters were similar in all groups. Cortical porosity was around 0.40% ± 0.15 and bone volume / total volume was around 0.22% ± 0.13. MTX-PG1 was found at similar levels in MTX groups and correlated negatively with AI in MTX alone or MTX and FA at the same day groups (p<0.05 and p<0.01, respectively). Finally, white and red blood cells, platelets, hemoglobin, mean corpuscular volume, transaminases, and creatinine were found at a similar level in MTX groups.ConclusionCo-administration of MTX with FA on the same day is effective compared to FA application one day after MTX. MTX metabolism was not affected, as demonstrated by the MTX-PG concentrations. The biological tolerance between the protocols was comparable. Thus, co-administration of MTX and FA seems to be possible and may be more convenient to the patients and improve compliance at the end.References[1]Albrecht K, Müller-Ladner U. Side effects and management of side effects of methotrexate in rheumatoid arthritis. Clin Exp Rheumatol 2010;28:S95-101.[2]Gaujoux-Viala C, et al. Recommendations of the French Society for Rheumatology for managing rheumatoid arthritis. Joint Bone Spine 2014;81:287–297.[3]Angelis-Stoforidis P, et al. Methotrexate polyglutamate levels in circulating erythrocytes and polymorphs correlate with clinical efficacy in rheumatoid arthritis. Clin Exp Rheumatol 1999;17:313–320.[4]Le Goff B, et al. A combination of methotrexate and zoledronic acid prevents bone erosions and systemic bone mass loss in collagen induced arthritis. Arthritis Res Ther 2009;11:R185.AcknowledgementsWe thank Ghislaine Roux, Diane Denis and Valentine Berrucas for their support in animal experiments. We thank Xavier Delavenne for MTX-PG dosage. We thank Nadia Boutahar for transaminases and creatinine dosage.Disclosure of InterestsElisa Dalix Grant/research support from: GEBRO, Mathieu Maalouf Grant/research support from: GEBRO, Sylvie Peyroche Grant/research support from: GEBRO, Arnaud Vanden-Bossche Grant/research support from: GEBRO, Charles-Antoine Arthaud Grant/research support from: GEBRO, Sophie Hodin Grant/research support from: GEBRO, Hubert MAROTTE Grant/research support from: GEBRO, Nordic Pharma, Rüdiger Müller Grant/research support from: GEBRO, Nordic Pharma
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Khanh, Tran Vu, Stefano Pinton, and Giuseppe Zampieri. "Loss of derivatives in the infinite type." Pure and Applied Mathematics Quarterly 11, no. 2 (2015): 315–27. http://dx.doi.org/10.4310/pamq.2015.v11.n2.a7.
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Frerick, Leonhard, Enrique Jordá, and Jochen Wengenroth. "Whitney extension operators without loss of derivatives." Revista Matemática Iberoamericana 32, no. 2 (2016): 377–90. http://dx.doi.org/10.4171/rmi/888.
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Cicognani, Massimo, and Ferruccio Colombini. "Loss of derivatives in evolution Cauchy problems." ANNALI DELL'UNIVERSITA' DI FERRARA 52, no. 2 (November 2006): 271–80. http://dx.doi.org/10.1007/s11565-006-0020-7.
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Fisher, S., S. L. Amacher, and M. E. Halpern. "Loss of cerebum function ventralizes the zebrafish embryo." Development 124, no. 7 (April 1, 1997): 1301–11. http://dx.doi.org/10.1242/dev.124.7.1301.
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Recent studies implicate ventrally derived signals, in addition to dorsal ones emanating from the organizer, in patterning the vertebrate gastrula. We have identified five overlapping deficiencies that uncover the zebrafish cerebum locus and dramatically alter dorsal-ventral polarity at gastrulation. Consistent with the properties of experimentally ventralized amphibian embryos, cerebum mutants exhibit reduced neurectodermal gene expression domains and an increase in derivatives of ventral mesoderm. Structures derived from paraxial and lateral mesoderm also are reduced; however, dorsal axial mesodermal derivatives, such as the hatching gland and notochord, are largely spared. The pleiotropic action of cerebum deficiencies, and the differential response of affected tissues, suggest that the cerebum gene may normally function as an inhibitor of ventralizing signals, a function previously ascribed to Noggin and Chordin in Xenopus. Analysis of the cerebum phenotype provides genetic evidence for the existence of ventralizing signals in the zebrafish gastrula and for antagonists of those signals.
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Taušer, J., and R. Čajka. "Weather derivatives and hedging the weather risks." Agricultural Economics (Zemědělská ekonomika) 60, No. 7 (July 18, 2014): 309–13. http://dx.doi.org/10.17221/11/2014-agricecon.
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The article focuses on weather derivatives with the aim to present the substance of weather derivatives as relatively new financial products and to discuss their advantages and disadvantages when being used as a tool to diminish the loses coming from these suboptimal weather conditions. We conclude with the findings that weather derivatives have a great potential to develop further. They provide an opportunity to hedge against the suboptimal weather conditions at reasonable costs. However, the hedging effectiveness is the main issue to be analyzed in each specific business case.
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Fang, Daoyuan, Xiaojun Lu, and Michael Reissig. "-loss of derivatives for an evolution type model." Nonlinear Analysis: Theory, Methods & Applications 71, no. 11 (December 2009): 5368–80. http://dx.doi.org/10.1016/j.na.2009.04.027.
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Nazal, Abdullah Ibrahim. "Problem of Companies Financial Analyses Derivatives Evaluation." JOURNAL OF SOCIAL SCIENCE RESEARCH 5, no. 2 (September 30, 2014): 717–22. http://dx.doi.org/10.24297/jssr.v5i2.3359.
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This article concentrates on derivatives evaluation in financial report. As result to search, derivatives have negative affection and positive affection practically. Derivatives have cost in current time but return in future is not clear because of expecting possibility. In spite of its cost it must give value to increase assets value or reduce liabilities value or reduce cost or reduce tax or make profit at time of making financial report. Negative affection comes from transfer risk of loss which transfers loosing responsibility it added new type of risk. By comparing between derivatives and traditional choices to face risk, there is different in evaluation as result to degree of responsibility, source of its value, Liquidity, currency risk, product market price risk, credit risk and linked with other selling contract risk. Searcher recommended to reduce ignorance by explains the real looser and looser ability to buy loss which limit derivatives transfer loss in order to make financial report useful. Its difficulty comes from promising to give product and promising to buy price in future regardless of loss which needs grantee to apply promising or give suitable compensation. Some things consider as standards may not accept expecting rules for pricing as some currencies price which just apply by monetary policy.
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Huang, Yue-Yue, Zi-Hao Wang, Li-Hui Deng, Hong Wang, and Qun Zheng. "Oral Administration of Quercetin or Its Derivatives Inhibit Bone Loss in Animal Model of Osteoporosis." Oxidative Medicine and Cellular Longevity 2020 (October 27, 2020): 1–21. http://dx.doi.org/10.1155/2020/6080597.
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Objectives. Quercetin (Q) and its derivatives are the major members of the naturally occurring flavonoid family, which possess beneficial effects on disease prevention including osteoporosis. The present study is aimed at further investigating the efficacy of the Q and its derivatives on bone pathology, bone-related parameters under imageology, bone maximum load, and serum bone metabolism indexes in animal model of osteoporosis. Potential mechanisms of Q and its derivatives in the treatment of osteoporosis as well as the existing problems regarding the modeling method and limitations of researches in this area were also summarized. Eight databases were searched from their inception dates to February 2020. Nineteen eligible studies containing 21 comparisons were identified ultimately. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately. The results displayed the number of criteria met varied from 3/10 to 7/10 with an average of 5.05. The present study provided the preliminary preclinical evidence that oral administration of Q or its derivatives was capable of improving bone pathology, bone-related parameters under imageology and bone maximum load, increasing serum osteocalcin, alkaline phosphatase, and estradiol, and reducing serum c-terminal cross-linked telopeptide of type I collagen ( P < 0.05 ). No statistical difference was seen in survival rate, index of liver, or kidney function ( P > 0.05 ). Q and its derivatives partially reverse osteopenia probably via antioxidant, anti-inflammatory, promoting osteogenesis, inhibiting osteoclasts, and its estrogen-like effect. The findings reveal the possibility of developing Q or its derivatives as a drug or an ingredient in diet for clinical treatment of osteoporosis.
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Heynderickx, Arnault, Sébastien Nénon, Olivier Siri, Vladimir Lokshin, and Vladimir Khodorkovsky. "1,2,3,4-Tetrahydro-1,4,5,8-tetraazaanthracene revisited: properties and structural evidence of aromaticity loss." Beilstein Journal of Organic Chemistry 15 (August 28, 2019): 2059–68. http://dx.doi.org/10.3762/bjoc.15.203.
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The synthesis and properties of 1,2,3,4-tetrahydro-1,4,5,8-tetraazaanthracene (THTAA) – a heterocycle involving both >N–H donating and =N– accepting moieties – have been reinvestigated. Unlike previously reported, THTAA is a thermally stable compound that can be re-sublimed at 300–310 °C without decomposition. Controlled introduction of substituents at the nitrogen atoms of THTAA led to variation of its electron donor/acceptor capability that allowed fine-tuning the absorption properties. The propensity of these compounds and a number of its derivatives to form infinite chains involving >N–H···N= and >N–H···Hal−···N+ atoms is demonstrated by X-ray structure analysis. The DFT level optimized and experimental geometry of THTAA and its derivatives show considerable loss of aromaticity within the quinoxaline moiety.
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PARENTI, Cesare, and Alberto PARMEGGIANI. "ON THE HYPOELLIPTICITY WITH A BIG LOSS OF DERIVATIVES." Kyushu Journal of Mathematics 59, no. 1 (2005): 155–230. http://dx.doi.org/10.2206/kyushujm.59.155.
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Gruzinskii, V. V., A. V. Kukhto, V. A. Suchkov, and S. M. Kazakov. "Electron Energy Loss Under Scattering by Naphthalimide Derivatives Vapours." Spectroscopy Letters 27, no. 1 (January 1994): 65–75. http://dx.doi.org/10.1080/00387019408002508.
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Iben, Ben, and Rupert Brotherton-Ratcliffe. "Credit Loss Distributions and Required Capital For Derivatives Portfolios." Journal of Fixed Income 4, no. 1 (June 30, 1994): 6–14. http://dx.doi.org/10.3905/jfi.1994.408101.
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Parmeggiani, Alberto, and Karel Pravda-Starov. "Semiclassical hypoelliptic estimates with a loss of many derivatives." Revista Matemática Iberoamericana 30, no. 4 (2014): 1439–78. http://dx.doi.org/10.4171/rmi/821.
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Möhrle, Hans, and Thomas Berkenkemper. "Oxidation von Methylpiperidin-Derivaten unter Berücksichtigung der Chiralität / Oxidation of Methylpiperidine Derivatives with Regard to Chirality." Zeitschrift für Naturforschung B 62, no. 12 (December 1, 2007): 1514–24. http://dx.doi.org/10.1515/znb-2007-1208.
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When 2-(2-methyl-1-piperidinyl)ethanol derivatives 3a and 3b were dehydrogenated with Hg(II)- EDTA, an iminium function involving the tertiary α-carbon atom of the piperidine ring is formed regioselectively. Cyclization of these intermediates yielded diastereomeric mixtures of oxazolidines 7a and 7b, in solutions of which hydroxy-enamine species 8a/9a and 8b/9b, respectively, could be detected by NMR spectroscopy. A hydroxy-enamine derived from 7a could be trapped by cycloaddition to tetrazine 10. Protonation of the oxazolidines generated the iminium salts 6a/6b・X with loss of a chirality center. For prevention of different directions of ring dehydrogenation in the 2-(3-methyl- 1-piperidinyl)ethanol compounds, the 6-position was blocked with two methyl groups. With amino alcohol 17, the isolation of one of the racemates in pure form was achieved, which by dehydrogenation produced a diastereoisomeric lactam mixture 18, as shown by NMR spectroscopy. Reaction of 2-(4-methyl-1-piperidinyl)ethanol 19 with Hg(II)-EDTA gave rise to a diastereomeric lactam mixture 21 in the ratio 60 : 40. From enantiomerically pure phenyloxiranes, the amino alcohols R(-)-19 and S(+)-19 became available. Their dehydrogenation under standardized conditions always showed a spreading range of isomeric lactams, which could not be separated.
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Andrés, Celia María Curieses, José Manuel Pérez de la Lastra, Celia Andrés Juan, Francisco J. Plou, and Eduardo Pérez-Lebeña. "Impact of Reactive Species on Amino Acids—Biological Relevance in Proteins and Induced Pathologies." International Journal of Molecular Sciences 23, no. 22 (November 14, 2022): 14049. http://dx.doi.org/10.3390/ijms232214049.
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This review examines the impact of reactive species RS (of oxygen ROS, nitrogen RNS and halogens RHS) on various amino acids, analyzed from a reactive point of view of how during these reactions, the molecules are hydroxylated, nitrated, or halogenated such that they can lose their capacity to form part of the proteins or peptides, and can lose their function. The reactions of the RS with several amino acids are described, and an attempt was made to review and explain the chemical mechanisms of the formation of the hydroxylated, nitrated, and halogenated derivatives. One aim of this work is to provide a theoretical analysis of the amino acids and derivatives compounds in the possible positions. Tyrosine, methionine, cysteine, and tryptophan can react with the harmful peroxynitrite or •OH and •NO2 radicals and glycine, serine, alanine, valine, arginine, lysine, tyrosine, histidine, cysteine, methionine, cystine, tryptophan, glutamine and asparagine can react with hypochlorous acid HOCl. These theoretical results may help to explain the loss of function of proteins subjected to these three types of reactive stresses. We hope that this work can help to assess the potential damage that reactive species can cause to free amino acids or the corresponding residues when they are part of peptides and proteins.
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Güemes-Vera, Norma. "Cereal and leguminose derivates in meat products elaboration." Nacameh 1, no. 2 (December 30, 2007): 110–17. http://dx.doi.org/10.24275/uam/izt/dcbs/nacameh/2007v1n2/guemes.
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Meil Landwerlin, Gerardo. "Los desafíos al sistema de protección social derivados de la postmodernización de la familia." Arbor CLXXIV, no. 685 (January 30, 2003): 163–93. http://dx.doi.org/10.3989/arbor.2003.i685.632.
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Holzegel, Gustav, Jonathan Luk, Jacques Smulevici, and Claude Warnick. "Asymptotic Properties of Linear Field Equations in Anti-de Sitter Space." Communications in Mathematical Physics 374, no. 2 (November 4, 2019): 1125–78. http://dx.doi.org/10.1007/s00220-019-03601-6.
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Abstract We study the global dynamics of the wave equation, Maxwell’s equation and the linearized Bianchi equations on a fixed anti-de Sitter (AdS) background. Provided dissipative boundary conditions are imposed on the dynamical fields we prove uniform boundedness of the natural energy as well as both degenerate (near the AdS boundary) and non-degenerate integrated decay estimates. Remarkably, the non-degenerate estimates “lose a derivative”. We relate this loss to a trapping phenomenon near the AdS boundary, which itself originates from the properties of (approximately) gliding rays near the boundary. Using the Gaussian beam approximation we prove that non-degenerate energy decay without loss of derivatives does not hold. As a consequence of the non-degenerate integrated decay estimates, we also obtain pointwise-in-time decay estimates for the energy. Our paper provides the key estimates for a proof of the non-linear stability of the anti-de Sitter spacetime under dissipative boundary conditions. Finally, we contrast our results with the case of reflecting boundary conditions.
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Bogacz, Roman, Kurt Frischmuth, and Krzysztof Lisowski. "Interface Conditions and Loss of Stability for Stepped Columns." Applied Mechanics and Materials 9 (October 2007): 41–50. http://dx.doi.org/10.4028/www.scientific.net/amm.9.41.
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We discuss the dynamic behavior of stepped columns subjected to follower forces. In particular, limit cases which correspond to columns with hinges or cracks and concentrated lateral supports are studied for the stability limit. Typically, solutions suffer jumps in certain derivatives, which have to satisfy compatibility conditions. The influence of these interface conditions on the critical force is investigated. The aim is to optimize the location of such singularities and thus to obtain maximum critical loads, respectively worst case estimates for the loss of stability.
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Lahiri, Somdeb. "Risk Aversion and a Calculus for Finitely Generated Piecewise Linear Functions: A Calculus that Economists Ought to Develop?" Metody Ilościowe w Badaniach Ekonomicznych 23, no. 1 (June 30, 2022): 1–10. http://dx.doi.org/10.22630/mibe.2022.23.1.1.
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In this note we propose a calculus for piece-wise linear functions, in order to obtain derivatives and second derivatives at points where the function is not differentiable. Such derivatives can be used to calculate coefficients of risk aversion at initial wealth for piece-wise linear utility functions for gains, which display loss aversion-and hence non differentiability at zero gains.
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Figlewski, Stephen. "How to Lose Money in Derivatives." Journal of Derivatives 2, no. 2 (November 30, 1994): 75–82. http://dx.doi.org/10.3905/jod.1994.407906.
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Li, Zehao, and Zeyuan Niu. "CITIC Pacific Hedging Strategy Analysis In 2008." BCP Business & Management 30 (October 24, 2022): 422–28. http://dx.doi.org/10.54691/bcpbm.v30i.2461.
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At 2008 CITIC Pacific incurred a huge loss of 51.5 million US dollars from its foreign currency derivatives contracts. The reason for such a huge loss is the misuse of a complex derivative called Knock Out Discount Accumulator (KODA). This article focuses on the mechanisms of such derivatives as well as how such mechanisms make CITIC Pacific take a huge loss. In this article, we find that the cumulative option contract has been widely recognized as one of the most effective hedging strategies against foreign exchange risk. However, the cumulative option entered by CITIC Pacific is unreasonable. We propose some suggestions for the firm to follow in order to help hedge the risk. Besides, what international trade companies can learn from this case is also talked about.