Oral tolerance to cancer can be abrogated by T regulatory cell inhibition

Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut

The wavelet-NARMAX representation : a hybrid model structure combining polynomial models with multiresolution wavelet decompositions

A new hybrid model structure combing polynomial models with multiresolution wavelet decompositions is introduced for nonlinear system identification. Polynomial models play an important role in approximation theory, and have been extensively used in linear and nonlinear system identification. Wavelet decompositions, in which the basis functions have the property of localization in both time and frequency, outperform many other approximation schemes and offer a flexible solution for approximating arbitrary functions. Although wavelet representations can approximate even severe nonlinearities in a given signal very well, the advantage of these representations can be lost when wavelets are used to capture linear or low-order nonlinear behaviour in a signal. In order to sufficiently utilise the global property of polynomials and the local property of wavelet representations simultaneously, in this study polynomial models and wavelet decompositions are combined together in a parallel structure to represent nonlinear input-output systems. As a special form of the NARMAX model, this hybrid model structure will be referred to as the WAvelet-NARMAX model, or simply WANARMAX. Generally, such a WANARMAX representation for an input-output system might involve a large number of basis functions and therefore a great number of model terms. Experience reveals that only a small number of these model terms are significant to the system output. A new fast orthogonal least squares algorithm, called the matching pursuit orthogonal least squares (MPOLS) algorithm, is also introduced in this study to determine which terms should be included in the final model

Impact factors for curved continuous CFST truss girder bridges

© 13th International Conference on Shock and Impact Loads on Structures, SILOS 2019. All Rights Reserved. A finite element model for curved continuous concrete-filled steel tubular (CFST) composite truss girder bridges has been built, and a new iterative process has been proposed for the analysis of the vehicle-bridge coupled system. The vibration modes and impact factors of the curved continuous CFST composite truss girder bridge have been obtained. The effects of parameters on the impact factors, such as the vehicle speed and deck unevenness, have been studied. The results show that the impact factor of the bridge is much larger than the value calculated from the current design code. The resonant critical vehicle speed and the resonant critical loading position are varied for different girder spans. The vehicle speed limit cannot effectively reduce the dynamic impact, and the bridge deck roughness excitation has an amplification effect on the impact factor causing by resonance. The results in this study are useful for design consideration and maintenance of CFST composite truss girder bridges

Expression, purification, and characterization of a novel Ca2+- and phospholipid-binding protein annexin B2

Annexin B2 (AnxB2) is a novel member of the annexin family of Ca2+- and phospholipid-binding proteins from Cysticercus cellulosae. To obtain highly pure AnxB2 with an easy and inexpensive purification approach, its cDNA was cloned into the prokaryotic expression vector pJLA503 and the translation initiation codon was immediately under the control of the inducible bacteriophage λ promoters PR and PL. After induction by shifting temperature, large amounts of non-fusion protein were produced in Escherichia coli in a soluble form. Then a novel purification method based on Ca2+-dependent phosphatidylserine (PS)-binding activity was established, whereby the purity of AnxB2 was increased to 98.7%. Western blot analysis showed that recombinant AnxB2 was specifically recognized by serum of pigs infected with cysticercosis. In vitro test showed that, the recombinant AnxB2 had anticoagulant activity and platelet binding activity. The expression, purification, and initial characterization of AnxB2 set an important stage for further characterization of the protein

Psychological and demographic factors affecting household energy-saving intentions: A TPB-based study in northwest China

Changing energy consumption behavior is a promising strategy to enhance household energy efficiency and to reduce carbon emission. Understanding the role of psychological and demographic factors in the context of energy-conservation behaviors is critical to promote energy-saving behaviors in buildings. This study first proposes a theoretical framework built on the Theory of Planned Behavior (TPB). Based on the collected survey data from 207 families (553 residents) in three communities in Xi’an, a typical city in northwest China, the research examines how three standard TPB predictors, namely attitude, subjective norm, and perceived behavioral control, as well as their interactive effects and three socio-demographic factors (i.e., house ownership, education and household income) influence building occupants’ energy-saving intention at home. Through structural equation modeling and keyword analysis, this study reveals that two interaction terms, namely attitude and subjective norms, as well as attitude and perceived behavior control, significantly influence building occupants’ energy-saving intention. Furthermore, this study implies that household income may positively associate with occupants’ energy-saving intention. The model in this study would be conducive to architects and property managers to mitigate severe building energy overuse problem in design and operation stages. Based on a qualitative analysis, the study then discusses the limitations of the study and further research direction. The results of this study would be conducive to building designers and operators to develop customized architectural or informatic interventions and to mitigate the severe energy overuse problem in the residential sector in northwest China.</jats:p

Self-Organized Ni Nanocrystal Embedded in BaTiO3 Epitaxial Film

Ni nanocrystals (NCs) were embedded in BaTiO3 epitaxial films using the laser molecular beam epitaxy. The processes involving the self-organization of Ni NCs and the epitaxial growth of BaTiO3 were discussed. With the in situ monitoring of reflection high-energy electron diffraction, the nanocomposite films were engineered controllably by the fine alternation of the self-organization of Ni NCs and the epitaxial growth of BaTiO3. The transmission electron microscopy and the X-ray diffraction characterization confirmed that the composite film consists of the Ni NCs layers alternating with the (001)/(100)-oriented epitaxial BaTiO3 separation layers

DAMA/LIBRA results and perspectives

The DAMA/LIBRA experiment, running at the Gran Sasso National Laboratory of the I.N.F.N. in Italy, has a sensitive mass of about 250 kg highly radiopure NaI(Tl). It is mainly devoted to the investigation of Dark Matter (DM) particles in the Galactic halo by exploiting the model independent DM annual modulation signature. The present DAMA/LIBRA experiment and the former DAMA/NaI one (the first generation experiment having an exposed mass of about 100 kg) have released so far results corresponding to a total exposure of 1.17 ton yr over 13 annual cycles. They provide a model independent evidence of the presence of DM particles in the galactic halo at 8.9 sigma C.L.. A short summary of the obtained results is presented and future perspectives of the experiment mentioned.Comment: 12 pages, Proceed. of the 15th Bled Workshop "What Comes Beyond Standard Models" (December 2012), Vol. 13, No.

Pulmonary vasoconstrictor action of KCNQ potassium channel blockers

KCNQ channels have been widely studied in the nervous system, heart and inner ear, where they have important physiological functions. Recent reports indicate that KCNQ channels may also be expressed in portal vein where they are suggested to influence spontaneous contractile activity. The biophysical properties of K+ currents mediated by KCNQ channels resemble a current underlying the resting K+ conductance and resting potential of pulmonary artery smooth muscle cells. We therefore investigated a possible role of KCNQ channels in regulating the function of pulmonary arteries by determining the ability of the selective KCNQ channel blockers, linopirdine and XE991, to promote pulmonary vasoconstriction. Linopirdine and XE991 both contracted rat and mouse pulmonary arteries but had little effect on mesenteric arteries. In each case the maximum contraction was almost as large as the response to 50 mM K+. Linopirdine had an EC50 of around 1 μM and XE991 was almost 10-fold more potent. Neither removal of the endothelium nor exposure to phentolamine or α,β-methylene ATP, to block α1-adrenoceptors or P2X receptors, respectively, affected the contraction. Contraction was abolished in Ca2+-free solution and in the presence of 1 μM nifedipine or 10 μM levcromakalim