Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of Src kinase by protein–tyrosine phosphatase–PEST in osteoclasts: Comparative analysis of the effects of bisphosphonate and protein–tyrosine phosphatase inhibitor on Src activation in vitro

PTP–PEST is involved in the regulation of sealing ring formation in osteoclasts. In this article, we have shown a regulatory role for PTP–PEST on dephosphorylation of c‐Src at Y527 and phosphorylation at Y418 in the catalytic site. Activation of Src in osteoclasts by over‐expression of PTP–PEST resulted in the phosphorylation of cortactin at Y421 and WASP at Y294. Also enhanced as a result, is the interaction of Src, cortactin, and Arp2 with WASP. Moreover, the number of osteoclasts displaying sealing ring and bone resorbing activity was increased in response to PTP–PEST over‐expression as compared with control osteoclasts. Cells expressing constitutively active‐Src (527YΔF) simulate the effects mediated by PTP–PEST. Treatment of osteoclasts with a bisphosphonate alendronate or a potent PTP inhibitor PAO decreased the activity and phosphorylation of Src at Y418 due to reduced dephosphorylation state at Y527. Therefore, Src‐mediated phosphorylation of cortactin and WASP as well as the formation of WASP·cortactin·Arp2 complex and sealing ring were reduced in these osteoclasts. Similar effects were observed in osteoclasts treated with an Src inhibitor PP2. We have shown that bisphosphonates could modulate the function of osteoclasts by inhibiting downstream signaling mediated by PTP–PEST/Src, in addition to its effect on the inhibition of the post‐translational modification of small GTP‐binding proteins such as Rab, Rho, and Rac as shown by others. The promising effects of the inhibitors PP2 and PAO on osteoclast function suggest a therapeutic approach for patients with bone metastases and osteoporosis as an alternative to bisphosphonates. J. Cell. Physiol. 220: 382–393, 2009. © 2009 Wiley‐Liss, Inc.
Supervisor Synthesis for Enforcing a Class of Generalized Mutual Exclusion Constraints on Petri Nets

The considered class of generalized mutual exclusion constraints (GMECs) on a controlled Petri net are such that the influence-uncontrollable subnets are forward-concurrent-free nets. Some structural properties of forward-concurrent-free nets are firstly proposed. Utilizing these properties, a method is then proposed to transform a given conjunction of GMECs into a conjunction of admissible GMECs. Furthermore, the necessary and sufficient condition of the existence of the permissive supervisor is obtained, and the optimal supervisor with a complexity of polynomial time is designed. The theoretic results are illustrated by an example that synthesizes a maximally permissive supervisor for a manufacturing system.
Contraction‐induced lipolysis is not impaired by inhibition of hormone‐sensitive lipase in skeletal muscle

• In skeletal muscle hormone‐sensitive lipase (HSL) is considered the only enzyme responsible for breakdown of intramyocellular triacylglycerol (IMTG) during contractions. This notion is based on indirect measures in which important cellular events are not taken into account. • Using two histochemical techniques to measure breakdown of IMTG during contractions in isolated skeletal muscles we found that IMTG was decreased (1) in rat muscles during acute pharmacological blockade of HSL, and (2) in muscles of HSL knockout mice. • We demonstrated that adipose triglyceride lipase (ATGL) and HSL collectively account for at least 98% of the total TG lipase activity in mouse muscle, and other TG lipases accordingly seem of negligible importance for breakdown of IMTG. • In conclusion, breakdown of IMTG occurs in the contracting muscle in the absence of HSL activity. Our data suggest that ATGL is activated during contractions and plays a major role in breakdown of IMTG.
Asymmetric Exchange Rate Pass-through and Monetary Policy in Open Economy

We extend the open economy model of optimal monetary policy to incorporate asymmetric exchange rate pass-through, with a focus on the effect of sticky price on monetary policy transmission and welfare analysis. Under incomplete pass-through in the home country and full pass-through in the foreign country, we find that country-specific productivity shocks have complex effects on optimal monetary policies, which also depend on the elasticity of money demand. In a world Nash equilibrium, foreign monetary policy depends on the degree of home exchange rate pass-through. Asymmetry in exchange rate pass-through leads to asymmetric welfare effects. The welfare level of the home country is higher than that of the foreign country in the Nash equilibrium. However, international cooperation can improve world welfare level.
Differential Effect of DDT, DDE, and DDD on COX‐2 Expression in the Human Trophoblast Derived HTR‐8/SVneo Cells

The purpose of this study was to investigate the effect of 1,1,1‐trichloro‐2,2‐bis‐(chlorophenyl)ethane (DDT), 1,1‐bis‐(chlorophenyl)‐2,2‐dichloroethene (DDE), and 1,1‐dichloro‐2,2‐bis(chlorophenyl)ethane (DDD) isomers on COX‐2 expression in a human trophoblast‐derived cell line. Cultured HTR‐8/SVneo trophoblast cells were exposed to DDT isomers and its metabolites for 24 h, and COX‐2 mRNA and protein expression were assessed by RT‐PCR, Western blotting, and ELISA. Prostaglandin E2 production was also measured by ELISA. Both COX‐2 mRNA and protein were detected under control (unexposed) conditions in the HTR‐8/SVneo cell line. COX‐2 protein expression and prostaglandin E2 production but not COX‐2 mRNA levels increased only after DDE and DDD isomers exposure. It is concluded that DDE and DDD exposure induce the expression of COX‐2 protein, leading to increased prostaglandin E2 production. Interestingly, the regulation of COX‐2 by these organochlorines pesticides appears to be at the translational level. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:454‐460, 2012; View this article online at wileyonlinelibrary.com. DOI 10:1002/jbt.21444
Protein structural similarities predicted by a sequence‐structure compatibility method

A method for protein structure prediction has been developed, which evaluates the compatibility of an amino acid sequence with known 3‐dimensional structures and identifies the most likely structure. The method was applied to a large number of sequences in a database, and the structures of the following proteins were predicted: (1) shikimate kinase (SKase), (2) the hydrophilic subunit of mannose permease (IIABMan), (3) rat tyrosine aminotransferase (Tyr AT), and (4) threonine dehydratase (TDH). The functional and evolutionary implications of the predictions are discussed. (1) The structural similarity between SKase and adenylate kinase was predicted. Alignment of their sequences reveals that the ATP‐binding type A sequence motif and 2 ATP‐binding arginine residues are conserved. The prediction suggests a similarity in their functional mechanisms as well as an evolutionary relationship. (2) The structural similarity between IIABMan and galactose/glucose‐binding protein (GGBP) was predicted. The IIA and IIB domains are aligned with the N‐and C‐terminal domains of GGBP, respectively. The 2 phosphorylated residues, His 10 and His 175, of IIABMan are threaded onto loops located in the substrate‐binding cleft of GGBP. The prediction accounts for the phosphoryl transfer from His 10 to His 175, and to the sugar substrate. (3) The structural similarity between rat Tyr AT and Escherichia coli aspartate AT was predicted, as well as (4) the structural similarity between TDH and the tryptophan synthase β subunit. Predictions (3) and (4) support the previous predictions based on observations of the functional similarities between the proteins.
Four Generations of Asset Pricing Models and Volatility Dynamics

The scope of this diploma thesis is to examine the four generations of asset pricing models and the corresponding volatility dynamics which have been devepoled so far. We proceed as follows: In chapter 1 we give a short repetition of the Black-Scholes first generation model which assumes a constant volatility and we show that volatility should not be modeled as constant by examining statistical data and introducing the notion of implied volatility. In chapter 2, we examine the simplest models that are able to produce smiles or skews - local volatility models. These are called second generation models. Local volatility models model the volatility as a function of the stock price and time. We start with the work of Dupire, show how local volatility models can be calibrated and end with a detailed discussion of the constant elasticity of volatility model. Chapter 3 focuses on the Heston model which represents the class of the stochastic volatility models, which assume that the volatility itself is driven by a stochastic process. These are called third generation models. We introduce the model structure, derive a partial differential pricing equation, give a closed-form solution for European calls by solving this equation and explain how the model is calibrated. The last part of chapter 3 then deals with the limits and the mis-specifications of the Heston model, in particular for recent exotic options like reverse cliquets, Accumulators or Napoleons. In chapter 4 we then introduce the Bergomi forward variance model which is called fourth generation model as a consequence of the limits of the Heston model explained in chapter 3. The Bergomi model is a stochastic local volatility model - the spot price is modeled as a constant elasticity of volatility diffusion and its volatility parameters are functions of the so called forward variances which are specified as stochastic processes. We start with the model specification, derive a partial differential pricing equation, show how the model has to be calibrated and end with pricing examples and a concluding discussion.
P2P-6 Trench-Isolated CMUT Arrays with a Supporting Frame

We present a trench-isolated CMUT process with a supporting mesh frame for a fully populated 2D array. In this process, the CMUT array is built on a silicon-on-insulator (SOI) wafer. Electrical interconnections to array elements are provided through the highly conductive silicon substrate. Neighboring array elements are separated from one another by trenches on both the device layer and the bulk silicon. A mechanically supporting frame is designed as a mesh structure between the silicon pillars providing electrical connections to the individual elements. Like the frameless trench isolation process, the framed trench isolation is compatible with both wafer-bonded and surface-micromachined CMUTs. In addition, this process eliminates the need for attaching the device wafer to a carrier wafer for the required mechanical support during the deep trench etching and flip-chip bonding steps, which presents difficulties during the release of the carrier wafer
Risk Prediction: A DWARF-like Approach

A large proportion of the most viable time series models used in empirical finance for density and value-at-risk forecasting are estimated with maximum likelihood methods. By way of its definition, the likelihood implicitly places equal weight on each of the observations in the sample, but this need not be optimal, depending on the extent to which the model and the true data generating process deviate. For example, in the context of modeling financial asset returns, schemes that place relatively more weight on observations in the recent past result in considerable improvement of out-of-sample density forecasts, compared with the default of equal weights. If instead of accurate forecasting of the, entire density, interest is restricted to just downside risk and risk model validation, then it would seem wise to (also) place more weight on the negative observations in the sample. In this paper, such weighted likelihood schemes are proposed and demonstrated to yield considerable improvements in forecast accuracy using a variety of data sets and different GARCH models. Further improvement is realized by combining the two weighting schemes, giving rise to a doubly weighted asymmetric risk forecasting method or, in short, a DWARF-like method.
Analytical expressions for the resonant frequencies and modal fields of finite coupled optical cavity chains

Coupled optical cavities are constantly attracting increased attention in telecommunication applications. For an infinite chain of optical cavities, also known as the coupled resonator optical waveguide (CROW), the tight binding approximation has been used in order to evaluate its dispersion characteristics and the modal fields. In this paper, the tight binding formalism is applied in a finite chain of optical cavities of arbitrary length. This allows the derivation of simple analytical formulas for the resonant frequencies and the corresponding modal fields. The analytical results are compared with the numerical results of the plane wave expansion method in the case of a finite two-dimensional photonic crystal chain of coupled resonators and an excellent agreement is observed.
Altered in vivo activity of liposome-incorporated lipopolysaccharide and lipid A

We compared the abilities of free and liposome-incorporated Salmonella minnesota wild-type lipopolysaccharide (LPS) and lipid A to activate peritoneal macrophages and induce lethal toxicity in mice. Incorporation of lipid A into multilamellar vesicles resulted in a 100-fold-decreased potency to prime macrophages for phorbol myristate acetate-triggered release of H2O2. In addition, liposome incorporation reduced the lethality of LPS and lipid A at least 10-fold in dactinomycin-sensitized mice. Similar results were obtained with multilamellar liposomes delivered intravenously and when small unilamellar vesicles were employed. The observed difference in toxicity was not dependent on dactinomycin treatment, since a similar decrease was obtained with large doses of liposomal LPS in unsensitized mice. Control liposomes, prepared without LPS and lipid A, did not reduce the activities of the free compounds. The administration of a sublethal amount of liposomal LPS induced within 20 days, but not during the first week, tolerance to a subsequently injected lethal dose of free endotoxin. The latter observation suggests that early-phase tolerance is not the mechanism responsible for the reduced toxicity of liposomal LPS. These data show that liposomal LPS and lipid A have reduced endotoxic activity in vivo and are consistent with our hypothesis that a direct interaction of lipid A with appropriate plasma membrane components is necessary to efficiently trigger biologic responses. This interaction, however, is prevented by the stable insertion of LPS into the liposomal membrane.
Caste development and evolution in ants: it's all about size

ABSTRACT Female ants display a wide variety of morphological castes, including workers, soldiers, ergatoid (worker-like) queens and queens. Alternative caste development within a species arises from a variable array of genetic and environmental factors. Castes themselves are also variable across species and have been repeatedly gained and lost throughout the evolutionary history of ants. Here, we propose a simple theory of caste development and evolution. We propose that female morphology varies as a function of size, such that larger individuals possess more queen-like traits. Thus, the diverse mechanisms that influence caste development are simply mechanisms that affect size in ants. Each caste-associated trait has a unique relationship with size, producing a phenotypic space that permits some combinations of worker- and queen-like traits, but not others. We propose that castes are gained and lost by modifying the regions of this phenotypic space that are realized within a species. These modifications can result from changing the size–frequency distribution of individuals within a species, or by changing the association of tissue growth and size. We hope this synthesis will help unify the literature on caste in ants, and facilitate the discovery of molecular mechanisms underlying caste development and evolution. Summary: Morphological castes in ants vary as a function of size, which has far-reaching consequences for caste development and evolution.
Effects of Endogenous Ovarian Estrogen Versus Exogenous Estrogen Replacement on Blood Flow and ERα and ERβ Levels in the Bladder

Objective. Determine the effect of endogenous estrogen versus estrogen replacement therapy (ERT) on bladder blood flow (BBF) and estrogen receptors (ERs). Methods. BBF was determined with radiolabeled microspheres in luteal, follicular, pregnant, oophorectomized (Ovx) sheep, and Ovx sheep with ERT. Estrogen receptors (ERα, ERβ) were quantified using Western blot analysis. Results. Compared to luteal and follicular ewes, BBF was reduced in pregnancy and following oophorectomy. Estrogen replacement therapy in Ovx sheep restored BBF to luteal levels. Estrogen receptor α predominated, whereas ERβ was not detectable. Estrogen receptor-α levels were unaffected by the ovarian cycle and increased in pregnancy, as well as in Ovx sheep with and without chronic ERT. Conclusion. The combination of diminished BBF and elevated ERα levels in both pregnant and Ovx sheep suggests an inverse relationship between BBF and ERα in the bladder. Although chronic ERT in Ovx sheep restored BBF, it did not restore ERα back to luteal levels.
Evolutionary Rate and Genetic Drift of Hepatitis C Virus Are Not Correlated with the Host Immune Response: Studies of Infected Donor-Recipient Clusters

ABSTRACT Six donor-recipient clusters of hepatitis C virus (HCV)-infected individuals were studied. For five clusters the period of infection of the donor could be estimated, and for all six clusters the time of infection of the recipients from the donor via blood transfusion was also precisely known. Detailed phylogenetic analyses were carried out to investigate the genomic evolution of the viral quasispecies within infected individuals in each cluster. The molecular clock analysis showed that HCV quasispecies within a patient are evolving at the same rate and that donors that have been infected for longer time tend to have a lower evolutionary rate. Phylogenetic analysis based on the split decomposition method revealed different evolutionary patterns in different donor-recipient clusters. Reactivity of antibody against the first hypervariable region (HVR1) of HCV in donor and recipient sera was evaluated and correlated to the calculated evolutionary rate. Results indicate that anti-HVR1 reactivity was related more to the overall level of humoral immune response of the host than to the HVR1 sequence itself, suggesting that the particular sequence of the HVR1 peptides is not the determinant of reactivity. Moreover, no correlation was found between the evolutionary rate or the heterogeneity of the viral quasispecies in the patients and the strength of the immune response to HVR1 epitopes. Rather, the results seem to imply that genetic drift is less dependent on immune pressure than on the rate of evolution and that the genetic drift of HCV is independent of the host immune pressure.
Outbred mice with long‐term Helicobacter felis infection develop both gastric lymphoid tissue and glandular hyperplastic lesions

Experimental infection of mice with Helicobacter felis reproduces many aspects of the gastritis observed in Helicobacter pylori‐infected humans. The development of gastric inflammatory lesions in chronically infected inbred mice is host‐dependent; in BALB/c mice, gastric B‐cell MALT lymphomas were observed, whilst other murine hosts (e.g. C57BL/6) developed severe glandular hyperplasia. The aims of this investigation were to characterize and immunophenotype Helicobacter‐induced inflammatory lesions in mice with an outbred genetic background. Swiss mice (n=10 per group) were either inoculated with a suspension of H. felis or left untreated. H. felis‐inoculated mice and age‐matched control animals were killed 13 months later. The severity of gastric inflammatory lesions in the animals was graded and the number and distribution of B (CD45R+) and T (CD3+) lymphocytes in lymphoid tissues was determined by immunohistochemistry. Compared with control mice, animals with long‐term H. felis infection developed severe hyperplastic gastritis (0.80±0.63 vs. 2.7±0.68), with epithelial dedifferentiation (0.40±0.52 vs. 2.3±0.82) and lengthening of the pits and glands (0.46±0.05 vs. 0.8±0.19). Gastric CD45R+ and CD3+ lymphocyte scores were significantly elevated (r=0.803) in infected animals, while lymphoepithelial lesions and polymorphonuclear leucocyte infiltrates were absent. Although prominent lymphoid follicles were present in the tissues of all infected animals, and in one control animal, only a proportion (55%) of the mucosal follicles had a dominant B‐cell phenotype (defined as ≥75% CD45R+ labelling), and all were poorly labelled with anti‐mouse immunoglobulin antibodies. It was concluded that the lesions in outbred Swiss mice differed from B‐cell MALT lymphomas. In contrast to inbred mice, outbred animals developed both glandular and lymphoid tissue lesions to chronic H. felis infection. It is suggested that the default T‐helper phenotype of the host influences glandular lesion formation or B‐cell lymphomagenesis in this model of infection. Copyright © 2000 John Wiley & Sons, Ltd.
Inhibition of cholesterol absorption by SCH 58053 in the mouse is not mediated via changes in the expression of mRNA for ABCA1, ABCG5, or ABCG8 in the enterocyte Published, JLR Papers in Press, August 16, 2002. DOI 10.1194/jlr.M200144-JLR200

Intestinal cholesterol absorption is a major determinant of plasma low density lipoprotein-cholesterol (LDL-C) concentrations. Ezetimibe (SCH 58235) and its analogs SCH 48461 and SCH 58053 are novel potent inhibitors of cholesterol absorption whose mechanism of action is unknown. These studies investigated the effect of SCH 58053 on cholesterol metabolism in female 129/Sv mice. In mice fed a low cholesterol rodent diet containing SCH 58053, cholesterol absorption was reduced by 46% and fecal neutral sterol excretion was increased 67%, but biliary lipid composition and bile acid synthesis, pool size, and pool composition were unchanged. When the dietary cholesterol content was increased either 10- or 50-fold, those animals given SCH 58053 manifested lower hepatic and biliary cholesterol concentrations than did their untreated controls. Cholesterol feeding increased the relative mRNA level for adenosine triphosphate-binding cassette transporter A1 (ABCA1), ABC transporter G5 (ABCG5), and ABC transporter G8 (ABCG8) in the jejunum, and of ABCG5 and ABCG8 in the liver, but the magnitude of this increase was generally less if the mice were given SCH 58053. We conclude that the inhibition of cholesterol absorption effected by this new class of agents is not mediated via changes in either the size or composition of the intestinal bile acid pool, or the level of mRNA expression of proteins that facilitate cholesterol efflux from the enterocyte, but rather may involve disruption of the uptake of luminal sterol across the microvillus membrane.