Miracle-dz/UniFAR-FTUs huggingface dataset:
-Tubulin and to Overcome Paclitaxel Resistance β The Seco-Taxane IDN5390 Is Able to Target Class III

A prominent mechanism of drug resistance to taxanes is the overexpression of class III B-tubulin. The seco-taxane IDN5390 was chosen for its selective activity in paclitaxel-resistant cells with an overexpression of class III B-tubulin. Moreover, the combined treatment paclitaxel/IDN5390 yielded a strong synergism, which was also evident in cell-free tubulin polymerization assays. In the presence of an anti-class III Btubulin as a blocking antibody, tubulin polymerization induced by paclitaxel and IDN5390 was enhanced and not affected, respectively, whereas synergism was abolished, thereby indicating that IDN5390 activity is not modulated by class III B-tubulin levels. Such properties can be explained by taking into consideration the composition of class III Btubulin paclitaxel binding site; in fact, Ser interacting with paclitaxel C group in class I is replaced by an Arginine in class III. IDN5390 that has an open and flexible C ring and an acidic A-unsaturated enol-keton moiety better fits with class III Btubulin than paclitaxel at the binding site. Taken altogether, these findings indicate that the concomitant treatment IDN5390/paclitaxel is able to successfully target class I and III B-tubulin and the combined use of two taxanes with diverse spectrum activity against tubulin isotypes could represent a novel approach to overcome paclitaxel resistance. (Cancer Res 2005; 65(6): 2397-405)
Iranian Journal of Basic Medical Sciences Cfp10: Mfcγ2 as a Novel Tuberculosis Vaccine Candidate Increases Immune Response in Mouse Introduction

Original article Objective(s): Despite treatment with antibiotics and vaccination with BCG, tuberculosis (TB) is still considered as one of the most important public health problems in the world. Therefore, designing and producing a more effective vaccine against TB seems urgently. In this study, immunogenicity of a fusion protein which consisting or comprising CFP-10 from Mycobacterium tuberculosis and the Fc-domain of mouse IgG2a was evaluated as a novel subunit vaccine candidate against TB. Materials and Methods: The genetic constructs were cloned in pPICZαA expression vector and recombinant vectors (pPICZαA-CFP-10: Fcγ2a and pPICZαA-CFP-10:His) were transformed into Pichia pastoris. To evaluate the expression of recombinant proteins, SDS-PAGE and immunoblotting were used. The immunogenicity of recombinant proteins, with and without BCG were assessed in BALB/c mice and specific cytokines against recombinant proteins (IFN-γ, IL-12, IL-4, IL-17 and TGF-β) were evaluated. Results: The levels of IFN-γ and IL-12 in mice that received recombinant proteins was higher than the control groups (BCG and PBS). Thus, both recombinant proteins (CFP-10:Fcγ2a and CFP-10:His) could excite good response in Th1-cells. The Fc-tagged protein had a stronger Th1 response with low levels of IL-4, as compared to CFP-10:His. However, the highest level of Th1 response was observed in groups that were vaccinated with BCG (prime) and then received recombinant protein CFP-10: Fcγ2a (booster). Conclusion: The results demonstrated that binding mice Fc-domain to CFP-10 protein can increase the immunogenicity of the subunit vaccine. Further studies, might be able to design and produce a new generation of subunit vaccines based on the Fc-fused immunogen. CFP10: mFcγ2 as a novel tuberculosis vaccine candidate increases immune response in mouse.
Signal characteristics of G protein‐transactivated EGF receptor

The epidermal growth factor receptor (EGFR) tyrosine kinase recently was identified as providing a link to mitogen‐activated protein kinase (MAPK) in response to G protein‐coupled receptor (GPCR) agonists in Rat‐1 fibroblasts. This cross‐talk pathway is also established in other cell types such as HaCaT keratinocytes, primary mouse astrocytes and COS‐7 cells. Transient expression of either Gq‐ or Gi‐coupled receptors in COS‐7 cells allowed GPCR agonist‐induced EGFR transactivation, and lysophosphatidic acid (LPA)‐generated signals involved the docking protein Gab1. The increase in SHC tyrosine phosphorylation and MAPK stimulation through both Gq‐ and Gi‐coupled receptors was reduced strongly upon selective inhibition of EGFR function. Inhibition of phosphoinositide 3‐kinase did not affect GPCR‐induced stimulation of EGFR tyrosine phosphorylation, but inhibited MAPK stimulation, upon treatment with both GPCR agonists and low doses of EGF. Furthermore, the Src tyrosine kinase inhibitor PP1 strongly interfered with LPA‐ and EGF‐induced tyrosine phosphorylation and MAPK activation downstream of EGFR. Our results demonstrate an essential role for EGFR function in signaling through both Gq‐ and Gi‐coupled receptors and provide novel insights into signal transmission downstream of EGFR for efficient activation of the Ras/MAPK pathway.
The Capacity of a Stegosystem for the Noisy Attack Channel

We consider a scenario where an attacker is able to receive a stegosignal only over a noisy channel under the condition that he (or she) may even know the cover message (CM). We propose to use a spread-spectrum-signal-based stegosystem (SG) and prove that the capacity of such SG is zero for any (cid:12)xed security level. Moreover, we show that the code rate satis(cid:12)es a square root law due to Ker et al. (in reality this law can be found in an earlier paper (2005) by the authors of the current paper). We get the same result for a conventional SG where the CM is modeled by a Gaussian correlated sequence with a correlation matrix unknown for the SG designer. We speculate that for any conventional SG with noiseless attack channel but for a practical CM model, the capacity should also be zero.
Monadic Second-Order Theories

In the present chapter we will make a case for the monadic second-order logic (that is to say, for the extension of first-order logic allowing quantification over monadic predicates) as a good source of theories that are both expressive and manageable. We will illustrate two powerful decidability techniques here—the one makes use of automata and games while the other uses generalized products a la Feferman-Vaught. The latter is, of course, particularly relevant, since monadic logic definitely appears to be the proper framework for examining generalized products. Undecidability proofs must be thought out anew in this area; for, whereas true first-order arithmetic is reducible to the monadic theory of the real line R, it is nevertheless not interpretable in the monadic theory of R. Thus, the examination of a quite unusual undecidability method is another subject that will be explained in this chapter. In the last section we will briefly review the history of the methods thus far developed and give a description of some further results. Monadic (second-order) logic is the extension of the first-order logic that allows quantification over monadic (unary) predicates. Thus, although binary, ternary, and other predicates, as well as functions, may appear in monadic (second-order) languages, they may nevertheless not be quantified over. 1.1. Formal Languages for Mathematical Theories We are interested less in monadic (second-order) logic itself than in the applications of this logic to mathematical theories. We are interested in the monadic formalization of the language of a mathematical theory and in monadic theories of corresponding mathematical objects. Before we explore this line of thought in more detail, let us argue that formalizing a mathematical language—not necessarily in monadic logic, but rather in first-order logic or in any other formal logic for that matter—can be useful.
Volcanic glass signatures in spectroscopic survey of newly proposed lunar pyroclastic deposits

Moon Mineralogy Mapper spectroscopic observations are used to assess the mineralogy of five sites that have recently been proposed to include lunar dark mantle deposits (DMDs). Volcanic glasses have, for the first time, clearly been identified at the location of three of the proposed pyroclastic deposits. This is the first time that volcanic glasses have been identified at such a small scale on the lunar surface from remote sensing observations. Deposits at Birt E, Schluter, and Walther A appear to be glassy DMDs. Deposits at Birt E and Schluter show (1) morphological evidence suggesting a likely vent and (2) mineralogical evidence indicative of the presence of volcanic glasses. The Walther A deposits, although they show no morphological evidence of vents, have the spectroscopic characteristics diagnostic of volcanic glasses. The deposits of the Freundlich‐Sharonov basin are separated in two areas: (1) the Buys‐Ballot deposits lack mineralogical and morphological evidence and thus are found to be associated with mare volcanism not with DMDs and (2) the Anderson crater deposits, which do not exhibit glassy DMD signatures, but they appear to be associated with possible vent structures and so may be classifiable as DMDs. Finally, dark deposits near the crater Kopff are found to be associated with likely mare volcanism and not associated with DMDs. The spectral identification of volcanic glass seen in many of the potential DMDs is a strong indicator of their pyroclastic origin.
Translational Research in Acute Lung Injury and Pulmonary Fibrosis Histone deacetylase inhibitors prevent pulmonary endothelial hyperpermeability and acute lung injury by regulating heat shock protein 90 function

Joshi AD, Barabutis N, Birmpas C, Dimitropoulou C, Thangjam G, Cherian-Shaw M, Dennison J, Catravas JD. Histone deacetylase inhibitors prevent pulmonary endothelial hyper-permeability and acute lung injury by regulating heat shock protein 90 function. Am J Physiol Lung Cell Mol Physiol 309: L1410–L1419, 2015. First published October 23, 2015; doi:10.1152/ajplung.00180. 2015. —Transendothelial hyperpermeability caused by numerous agonists is dependent on heat shock protein 90 (Hsp90) and leads to endothelial barrier dysfunction (EBD). Inhibition of Hsp90 protects and restores transendothelial permeability. Hyperacetylation of Hsp90, as by inhibitors of histone deacetylase (HDAC), suppresses its chaperone function and mimics the effects of Hsp90 inhibitors. In this study we assessed the role of HDAC in mediating lipopolysaccharide (LPS)-induced transendothelial hyperpermeability and acute lung injury (ALI). We demonstrate that HDAC inhibition protects against LPS-mediated EBD. Inhibition of multiple HDAC by the general inhibitors panobinostat or trichostatin provided protection against LPS-induced transendothelial hyperpermeability, acetylated and suppressed Hsp90 chaperone function, and attenuated RhoA activity and signaling crucial to endothelial barrier function. Treatment with the HDAC3-selective inhibitor RGFP-966 or the HDAC6selective inhibitor tubastatin A provided partial protection against LPS-mediated transendothelial hyperpermeability. Similarly, knock down of HDAC3 and HDAC6 by specific small-interfering RNAs provided significant protection against LPS-induced EBD. Furthermore, combined pharmacological inhibition of both HDAC3 and -6 attenuated the inflammation, capillary permeability, and structural abnormalities associated with LPS-induced ALI in mice. Together these data indicate that HDAC mediate increased transendothelial hyperpermeability caused by LPS and that inhibition of HDAC protects against LPS-mediated EBD and ALI by suppressing Hsp90dependent RhoA activity and signaling.
Intrahousehold Allocation of Education Expenditure and Returns to Education: The Case of Sri Lanka

This paper uses demand analysis to explore whether intrahousehold allocation of education expenditure differs between boys and girls in rural Sri Lanka. Contrary to most countries in South Asia a significant bias favouring girls is found in 1990/91 for the 5-9 and 17-19 age groups and in 1995/96 for the 5-9 and 14-16 age groups. The 5-9 age group captures the run-up to the Year 5 scholarship exams that are used to gain entry into better performing secondary schools. The 14-16 and 17-19 age groups capture those who read for important National level qualifications vital in the job market. The paper argues that these household level decisions are rational because wage returns to junior and senior secondary education have been higher for females than for males through the 1980s and 1990s.
Hyperoxia-Induced Protein Alterations in Renal Rat Tissue: A Quantitative Proteomic Approach to Identify Hyperoxia-Induced Effects in Cellular Signaling Pathways

Introduction. In renal tissue as well as in other organs, supranormal oxygen pressure may lead to deleterious consequences on a cellular level. Additionally, hyperoxia-induced effect in cells and related free radicals may potentially contribute to renal failure. The aim of this study was to analyze time-dependent alterations of rat kidney protein expression after short-term normobaric hyperoxia using proteomics and bioinformatic approaches. Material and Methods. N = 36 Wistar rats were randomized into six different groups: three groups with normobaric hyperoxia (exposure to 100% oxygen for 3 h) and three groups with normobaric normoxia (NN; room air). After hyperoxia exposure, kidneys were removed immediately, after 3 days and after 7 days. Kidney lysates were analyzed by two-dimensional gel electrophoresis followed by peptide mass fingerprinting using tandem mass spectrometry. Statistical analysis was performed with DeCyder 2D software (p < 0.01). Biological functions of differential regulated proteins were studied using functional network analysis (Ingenuity Pathways Analysis and PathwayStudio). Results. Expression of 14 proteins was significantly altered (p < 0.01): eight proteins (MEP1A_RAT, RSSA_RAT, F16P1_RAT, STML2_RAT, BPNT1_RAT, LGMN_RAT, ATPA_RAT, and VDAC1_RAT) were downregulated and six proteins (MTUS1_RAT, F16P1_RAT, ACTG_RAT, ACTB_RAT, 2ABA_RAT, and RAB1A_RAT) were upregulated. Bioinformatic analyses revealed an association of regulated proteins with inflammation. Conclusions. Significant alterations in renal protein expression could be demonstrated for up to 7 days even after short-term hyperoxia. The identified proteins indicate an association with inflammation signaling cascades. MEP1A and VDAC1 could be promising candidates to identify hyperoxic injury in kidney cells.
Do Hypothetical and Actual Marginal Willingness to Pay Differ in Choice Experiments?: Application to the Valuation of the Environment

In this paper we test the validity of choice experiments with donations for environmental projects. In particular, we test whether or not willingness to pay for projects differs between a hypothetical and an actual choice experiment. Our results do not indicate that choice experiments suffer from overstatement in hypothetical willingness to pay; and this contrasts the results found in external tests of validity in Contingent Valuation. In addition, internal tests of validity indicate transitive and stable preferences in both experiments.
Integrin Clustering Is Driven by Mechanical Resistance from the Glycocalyx and the Substrate

Integrins have emerged as key sensory molecules that translate chemical and physical cues from the extracellular matrix (ECM) into biochemical signals that regulate cell behavior. Integrins function by clustering into adhesion plaques, but the molecular mechanisms that drive integrin clustering in response to interaction with the ECM remain unclear. To explore how deformations in the cell-ECM interface influence integrin clustering, we developed a spatial-temporal simulation that integrates the micro-mechanics of the cell, glycocalyx, and ECM with a simple chemical model of integrin activation and ligand interaction. Due to mechanical coupling, we find that integrin-ligand interactions are highly cooperative, and this cooperativity is sufficient to drive integrin clustering even in the absence of cytoskeletal crosslinking or homotypic integrin-integrin interactions. The glycocalyx largely mediates this cooperativity and hence may be a key regulator of integrin function. Remarkably, integrin clustering in the model is naturally responsive to the chemical and physical properties of the ECM, including ligand density, matrix rigidity, and the chemical affinity of ligand for receptor. Consistent with experimental observations, we find that integrin clustering is robust on rigid substrates with high ligand density, but is impaired on substrates that are highly compliant or have low ligand density. We thus demonstrate how integrins themselves could function as sensory molecules that begin sensing matrix properties even before large multi-molecular adhesion complexes are assembled.
Doing Work Based Research: Approaches to Enquiry for Insider-Researchers

With the growth of work based learning and practitioner research this book leads the way by addressing key issues faced by 'insider-researchers' - learners, practitioners and managers doing research projects in the organizations and communities in which they themselves work, or where they are already familiar with the setting. The authors explore the implications of these research contexts, and discuss approaches and methodologies that work based researchers might adopt, with a particular focus on ethics - one of the key concerns for those undertaking a research project of this type. This book is an authoritative and readable guide to the theory and practice of work based research. It is for anyone undertaking a research project based on work practice, including learners on postgraduate, undergraduate and doctoral programmes. Practitioners, managers and participants in work based courses or modules in education, healthcare and business management, will find it particularly useful.
Dielectric and thermal properties of nanostructured epoxy composites involving reactive POSS and c-BN

Epoxy composites containing either Polyhedral Oligomeric Silsesquioxanes (POSS) or cubic boron nitride (c-BN), in addition to a multiphase composite with both, POSS and c-BN, were fabricated and studied. A reactive liquid POSS, namely a Triglycidylisobutyl-POSS (TGIB-POSS) was used in a content of 1 wt% for the single phase and the multiphase composite. Submicrometric c-BN was used in a content of 5 wt% for the respective single phase composite as well as in the multiphase sample to create multifunctional nanostructured composites. The test specimens were characterized by Broadband Dielectric Spectroscopy (BDS) and thermal conductivity measurements. While the single phase POSS composite revealed a slightly enhanced thermal conductivity, the single phase c-BN composite showed an improvement by 26 % in thermal conductivity compared to neat epoxy. Additionally, the dielectric and thermal properties of the multiphase composite containing 1 wt% POSS and 5 wt% c-BN, were found to be dictated by the submicrometric c-BN particles.
Chemical composition of atmospheric aerosols from Zhenbeitai, China, and Gosan, South Korea, during ACE‐Asia

[1] Studies were conducted as part of Asian Pacific Regional Aerosol Characterization Experiment (ACE-Asia) to characterize the major ion and elemental composition of aerosol particle samples collected at Gosan, an ACE-Asia supersite (GOS, Korea, total suspended particle or TSP samples) and at Zhenbeitai (ZBT, China, TSP and particles < 2.5 mm diameter or PM2.5 samples), a site closer to the sources for Asia dust. The concentrations of 24 elements in the ZBT PM2.5 samples were correlated with Al (an indicator of mineral dust), and the ratios of these elements to Al were similar to those in a loess certified reference material, but a second group of elements was enriched over crustal proportions most likely as a result of pollution emissions. The concentrations of various water-soluble (WS) cations (Na + ,K + ,C a 2+ ,M g 2+ ) also were generally well correlated with Al in both the ZBT and GOS samples, with the exception being WS K + at ZBT, where biomass burning may have had an effect. The percentage of calcium that was soluble approached 100% at ZBT versus � 60% at GOS, and the ratio WS Ca 2+ /Al also was higher at ZBT. The molar ratio of sulfate to WS Ca 2+ was � 0.1 at ZBT but increased to near unity at GOS, where the aerosol nitrate/WS Ca 2+ ratio was tenfold to hundredfold higher compared with ZBT, presumably because of anthropogenic influences. The observed differences in aerosol characteristics between sites can only be explained as the end product of different source contributions combined with complex processes involving gas-particle conversion, size-dependent fractionation, and aerosol mixing. INDEX TERMS: 0305 Atmospheric Composition and Structure: Aerosols and particles (0345, 4801); 0330 Atmospheric Composition and Structure: Geochemical cycles; 0365 Atmospheric Composition and Structure: Troposphere—composition and chemistry; 0368 Atmospheric Composition and Structure: Troposphere—constituent transport and chemistry; 9320 Information Related to Geographic Region: Asia; KEYWORDS: aerosol, biogeochemistry, atmospheric dust, air pollution, Asia
Response to Ameisen

We thank Dr Ameisen for his interest on our manuscript (Addolorato et al ., 2011) and appreciate the opportunity to respond to his comments. As noted by Dr Ameisen (Ameisen, 2011), in our manuscript, we refer not only to his case report (Ameisen, 2005), but also to the case report by Bucknam (2007). We appreciate Dr Ameisen's clarification that in his own case report high-dose baclofen suppressed (as opposed to reduced) alcohol craving and consumption. Dr Ameisen correctly states that Bucknam's title and abstract report the word ‘suppression’; however, the full-length text of Bucknam (2007) leads to the surprising discovery that the patient described a dramatic reduction (but not suppression) in alcohol craving and consumption. We did not mean to misinterpret Dr Ameisen's opinion. Rather, we provided an overall ‘take home’ message based on both case reports (Ameisen, 2005; Bucknam, 2007) given that high-dose baclofen did not have an identical effect in these two patients. (We would point out too, that in Agabio's case report (Agabio et al ., 2007), mentioned by Dr Ameisen where the patient's alcohol …
Channelling The Nigeria’s Foreign Exchange Reserves into Alternative Investment Outlets: A Critical Analysis

In recent years, impressive price of crude oil has stimulated the accumulation of foreign exchange reserves in Nigeria. However, observers have expressed fears about the channels of utilisation of the reserves, especially to other alternatives investment outlets. This paper examines the cost-effective propositions of the foreign reserves in Nigeria, and considers alternative investment channels. The study uses data from publications of the Central Bank of Nigeria (CBN), Statistical Bulletin, Annual Reports and Statement of Accounts. It adopts the theory of demand for internationalreserves based on three motive notably transaction, precautionary and mercantilist. The study among others finds that Nigeria foreign reserve is adequate. The level of reserves to import satisfies the international benchmark etc. The study recommends among others the need to split foreign reserves into four portfolios. The liquidity portfolio, long-term portfolio or investment portfolio, immunization portfolio, and the petroleum fund buffer portfolio or sovereign wealth fund.