Forced unfolding modulated by disulfide bonds in the Ig domains of a cell adhesion molecule

Cell adhesion molecules (CAMs) mediate cell attachment and stress transfer through extracellular domains. Here we forcibly unfold the Ig domains of a prototypical Ig superfamily CAM that contains intradomain disulfide bonds. The Ig domains of all such CAMs have conformations homologous to cadherin extracellular domains, titin Ig-type domains, and fibronectin type-III (FNIII) domains. Atomic force microscopy has been used to extend the five Ig domains of Mel-CAM (melanoma CAM)—a protein that is overexpressed in metastatic melanomas—under conditions where the disulfide bonds were either left intact or disrupted through reduction. Under physiological conditions where intradomain disulfide bonds are intact, partial unfolding was observed at forces far smaller than those reported previously for either titin's Ig-type domains or tenascin's FNIII domains. This partial unfolding under low force may be an important mechanism for imparting elasticity to cell–cell contacts, as well as a regulatory mechanism for adhesive interactions. Under reducing conditions, Mel-CAM's Ig domains were found to fully unfold through a partially folded state and at slightly higher forces. The results suggest that, in divergent evolution of all such domains, stabilization imparted by disulfide bonds relaxes requirements for strong, noncovalent, folded-state interactions.

DEG/ENaC ion channels involved in sensory transduction are modulated by cold temperature

Several DEG/ENaC cation channel subunits are expressed in the tongue and in cutaneous sensory neurons, where they are postulated to function as receptors for salt and sour taste and for touch. Because these tissues are exposed to large temperature variations, we examined how temperature affects DEG/ENaC channel function. We found that cold temperature markedly increased the constitutively active Na+ currents generated by epithelial Na+ channels (ENaC). Half-maximal stimulation occurred at 25°C. Cold temperature did not induce current from other DEG/ENaC family members (BNC1, ASIC, and DRASIC). However, when these channels were activated by acid, cold temperature potentiated the currents by slowing the rate of desensitization. Potentiation was abolished by a “Deg” mutation that alters channel gating. Temperature changes in the physiologic range had prominent effects on current in cells heterologously expressing acid-gated DEG/ENaC channels, as well as in dorsal root ganglion sensory neurons. The finding that cold temperature modulates DEG/ENaC channel function may provide a molecular explanation for the widely recognized ability of temperature to modify taste sensation and mechanosensation.

Evidence that the 50-kDa substrate of brefeldin A-dependent ADP-ribosylation binds GTP and is modulated by the G-protein beta gamma subunit complex.

Brefeldin A, a fungal metabolite that inhibits membrane transport, induces the mono(ADP-ribosyl)ation of two cytosolic proteins of 38 and 50 kDa as judged by SDS/PAGE. The 38-kDa substrate has been previously identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We report that the 50-kDa BFA-induced ADP-ribosylated substrate (BARS-50) has native forms of 170 and 130 kDa, as determined by gel filtration of rat brain cytosol, indicating that BARS-50 might exist as a multimeric complex. BARS-50 can bind GTP, as indicated by blot-overlay studies with [alpha-32P]GTP and by photoaffinity labeling with guanosine 5'-[gamma-32P] [beta,gamma-(4-azidoanilido)]triphosphate. Moreover, ADP-ribosylation of BARS-50 was completely inhibited by the beta gamma subunit complex of G proteins, while the ADP-ribosylation of GAPDH was unmodified, indicating that this effect was due to an interaction of the beta gamma complex with BARS-50, rather than with the ADP-ribosylating enzyme. Two-dimensional gel electrophoresis and immunoblot analysis shows that BARS-50 is a group of closely related proteins that appear to be different from all the known GTP-binding proteins.

Por outras espacialidades: uma cartografia da pedagogização no Parque Ibirapuera, SP

O presente trabalho tem como propósito principal perspectivar analiticamente como os processos de pedagogização forjam e governam determinados espaços e espacialidades. Para tanto, partimos do pressuposto de que as práticas sociais são moduladas por jogos de força que as criam e recriam espacialmente, sobretudo por meio de mecanismos pedagogizantes que ultrapassam o âmbito educacional formal, alastrando-se cada vez mais no cenário urbano contemporâneo. Assim, propomo-nos a analisar a relação entre educação e produção de espaços/espacialidades nas práticas instituídas no Parque Ibirapuera-SP. A investigação tem como marco teórico o pensamento de Michel Foucault, além de mobilizar os trabalhos de Doreen Massey, Edward Soja, Henri Lefebvre, David Harvey e Rodrigo Valverde. A cartografia realizada pleiteia-se, portanto, uma derivação da perspectiva arqueogenealógica foucaultiana. De acordo com tal referencial, assinalaram-se práticas que permitiram dimensionar as transformações pedagógicas e espaciais do Parque desde sua criação, apontando para os modos como atualmente se perfaz o governamento das espacialidades e, em igual medida, as contracondutas aí tornadas possíveis. Além do levantamento bibliográfico, operamos segundo duas frentes de trabalho complementares: em primeiro lugar, a análise de documentos oficiais acerca do Parque, dos Processos da Comissão do IV Centenário da Cidade de São Paulo e de discursos jornalísticos veiculados a seu respeito pelo jornal O Estado de S. Paulo em diferentes décadas; em segundo, a observação e o registro de práticas contemporâneas ali em curso. Os resultados evidenciam uma racionalidade vincada em práticas de pedagogização, e estas, aliadas a tecnologias específicas de governamento dos espaços. Um cenário que apresenta lógicas de governo heterogêneas, que coexistem através do tempo, ajustando-se, desajustando-se ou alterando-se. Não obstante, um campo vivo de forças, de sujeitos e práticas de subjetivação. A história arqueogenealógica do Parque, assim como dos diferentes mecanismos pedagogizantes ali em voga, possibilitou deslindar o trânsito dos espaços e o governo das espacialidades pela população que dele faz uso, além das diferentes contestações dos arranjos até então configurados, demarcando traços fugidios de uma heterotopia urbana.

Two Consistent Many-Valued Logics for Paraconsistent Phenomena

In this reviewing paper, we recall the main results of our papers [24, 31] where we introduced two paraconsistent semantics for Pavelka style fuzzy logic. Each logic formula a is associated with a 2 x 2 matrix called evidence matrix. The two semantics are consistent if they are seen from 'outside'; the structure of the set of the evidence matrices M is an MV-algebra and there is nothing paraconsistent there. However, seen from "inside,' that is, in the construction of a single evidence matrix paraconsistency comes in, truth and falsehood are not each others complements and there is also contradiction and lack of information (unknown) involved. Moreover, we discuss the possible applications of the two logics in real-world phenomena.

Kink stability, propagation, and length-scale competition in the periodically modulated sine-gordon equation

We have examined the dynamical behavior of the kink solutions of the one-dimensional sine-Gordon equation in the presence of a spatially periodic parametric perturbation. Our study clarifies and extends the currently available knowledge on this and related nonlinear problems in four directions. First, we present the results of a numerical simulation program that are not compatible with the existence of a radiative threshold predicted by earlier calculations. Second, we carry out a perturbative calculation that helps interpret those previous predictions, enabling us to understand in depth our numerical results. Third, we apply the collective coordinate formalism to this system and demonstrate numerically that it reproduces accurately the observed kink dynamics. Fourth, we report on the occurrence of length-scale competition in this system and show how it can be understood by means of linear stability analysis. Finally, we conclude by summarizing the general physical framework that arises from our study.

Size-Dependent and Step-Modulated Supramolecular Electrochemical Properties of Catechol-Derived Adlayers at Pt(hkl) Surfaces

The electrochemical reactivity of catechol-derived adlayers is reported at platinum (Pt) single-crystal electrodes. Pt(111) and stepped vicinal surfaces are used as model surfaces possessing well-ordered nanometer-sized Pt(111) terraces ranging from 0.4 to 12 nm. The electrochemical experiments were designed to probe how the control of monatomic step-density and of atomic-level step structure can be used to modulate molecule–molecule interactions during self-assembly of aromatic-derived organic monolayers at metallic single-crystal electrode surfaces. A hard sphere model of surfaces and a simplified band formation model are used as a theoretical framework for interpretation of experimental results. The experimental results reveal (i) that supramolecular electrochemical effects may be confined, propagated, or modulated by the choice of atomic level crystallographic features (i.e.monatomic steps), deliberately introduced at metallic substrate surfaces, suggesting (ii) that substrate-defect engineering may be used to tune the macroscopic electronic properties of aromatic molecular adlayers and of smaller molecular aggregates.

Torn between state and market: Private policy implementation and conflicting institutional logics

Policy implementation by private actors constitutes a “missing link” for understanding the implications of private governance. This paper proposes and assesses an institutional logics framework that combines a top-down, policy design approach with a bottom-up, implementation perspective on discretion. We argue that the conflicting institutional logics of the state and the market, in combination with differing degrees of goal ambiguity, accountability and hybridity play a crucial role for output performance. These arguments are analyzed based on a secondary analysis of seven case studies of private and hybrid policy implementation in diverging contexts. We find that aligning private output performance with public interests is at least partly a question of policy design congruence: private implementing actors tend to perform deficiently when the conflicting logics of the state and the market combine with weak accountability mechanisms.

How Much am I Expected to Pay for my Parents‘ Firm? An Institutional Logics Perspective on Family Discounts

Recent evidence suggests that successors do not simply inherit their parents’ firm, but have to pay a certain price. Building on institutional logics literature, we explore successors’ family discount expectations, defined as the rebate expected from parents in comparison to nonfamily buyers when assuming control of the firm. We find that family cohesion increases discount expectations, while successors’ fear of failure and family equity stake in the firm decrease discount expectations. Higher education in business or economics weakens These effects. On average, in our study comprised of 16 countries, successors expect a 57% family discount.

Modulated entry /

"The technique of modulation, or variable coefficients, is discussed and the analytical formulation is reviewed. Representative numerical results of the use of modulation are shown for the lifting and nonlifting cases. These results include the effects of modulation on peak acceleration, entry corridor, and heat absorption. Results are given for entry at satellite speed and escape speed. The indications are that coefficient modulation on a vehicle with good lifting capability offers the possibility of sizable loading reductions or, alternatively, wider corridors; thus, steep entries become practical from the loading standpoint. The amount of steepness depends on the acceptable heating penalty. The price of sizable fractions of the possible gains does not appear to be excessive."

INDIRAD : a digital receiver for amplitude modulated signals using Indicator processing /

Thesis (M.S.)--University of Illinois at Urbana-Champaign.

Investigation of the starch gelatinisation phenomena in water-glycerol systems: application of modulated temperature differential scanning calorimetry

The use of modulated temperature differential scanning calorimetry (MTDSC) has provided further insight into the gelatinisation process since it allows the detection of glass transition during gelatinisation process. It was found in this work that the glass transition overlapped with the gelatinisation peak temperature for all maize starch formulations studied. Systematic investigation on maize starch gelatinisation over a range of water-glycerol concentrations with MTDSC revealed that the addition of glycerol increased the gelatinisation onset temperature with an extent that depended on the water content in the system. Furthermore, the addition of glycerol promoted starch gelatinisation at low water content (0.4 g water/g dry starch) and the enthalpy of gelatinisation varied with glycerol concentration (0.73-19.61 J/g dry starch) depending on the water content and starch type. The validities of published gelatinisation models were explored. These models failed to explain the glass transition phenomena observed during the course of gelatinisation and failed to describe the gelatinisation behaviour observed over the water-glycerol concentrations range investigated. A hypothesis for the mechanisms involved during gelatinisation was proposed based on the side chain liquid crystalline polymer model for starch structure and the concept that the order-disorder transition in starch requires that the hydrogen bonds (the major structural element in the granule packing) to be broken before the collapse of order (helix-coil transition) can take place. (C) 2004 Elsevier Ltd. All rights reserved.

Wheat grain cooking process as investigated by modulated temperature differential scanning calorimetry

The thermal properties of soft and hard wheat grains, cooked in a steam pressure cooker, as a function of cooking temperature and time were investigated by modulated temperature differential scanning calorimetry (MTDSC). Four cooking temperatures (110, 120, 130 and 140 degrees C) and six cooking times (20, 40, 60, 80, 100 and 120 min) for each temperature were studied. It was found that typical non-reversible heat flow thermograms of cooked and uncooked wheat grains consisted of two endothermic baseline shifts localised around 40-50 degrees C and then 60-70 degrees C. The second peaks of non-reversible heat flow thermograms (60-70 degrees C) were associated with starch gelatinisation. The degree of gelatinisation was quantified based on these peaks. In this study, starch was completely gelatinised within 60-80 min for cooking temperatures at 110-120 degrees C and within 20 min for cooking temperatures at 130-140 degrees C. MTDSC detected reversible endothermic baseline shifts in most samples, localised broadly around 48-67 degrees C with changes in heat capacity ranging from 0.02 to 0.06 J/g per degrees C. These reversible endothermic baseline shifts are related to the glass transition, which occurs during starch gelatinisation. Data on the specific heat capacity of the cooked wheat samples are provided. (C) 2005 Elsevier Ltd. All rights reserved.

No-switching quantum key distribution using broadband modulated coherent light

We realize an end-to-end no-switching quantum key distribution protocol using continuous-wave coherent light. We encode weak broadband Gaussian modulations onto the amplitude and phase quadratures of light beams. Our no-switching protocol achieves high secret key rate via a post-selection protocol that utilizes both quadrature information simultaneously. We establish a secret key rate of 25 Mbits/s for a lossless channel and 1 kbit/s for 90% channel loss, per 17 MHz of detected bandwidth, assuming individual Gaussian eavesdropping attacks. Since our scheme is truly broadband, it can potentially deliver orders of magnitude higher key rates by extending the encoding bandwidth with higher-end telecommunication technology.

TRAP220 is modulated by the antineoplastic agent 6-Mercaptopurine, and mediates the activation of the NR4A subgroup of nuclear receptors

The NR4A1-3 (Nur77, NURR1 and NOR-1) subfamily of nuclear hormone receptors (NRs) has been implicated in Parkinson's disease, schizophrenia, manic depression, atherogenesis, Alzheimer's disease, rheumatoid arthritis, cancer and apoptosis. This has driven investigations into the mechanism of action, and the identification of small molecule regulators, that may provide the platform for pharmaceutical and therapeutic exploitation. Recently, we found that the purine antimetabolite 6-Mercaptopurine (6-MP), which is widely used as an anti-neoplastic and anti-inflammatory drug, modulated the NR4A1-3 subfamily. Interestingly, the agonist-mediated activation did not involve modulation of primary coactivators' (e.g. p300 and SRC-2/GRIP-1) activity and/or recruitment. However, the role of the subsequently recruited coactivators, for example CARM-1 and TRAP220, in 6-MP-mediated activation of the NR4A1-3 subfamily remains obscure. In this study we demonstrate that 6-MP modulates the activity of the coactivator TRAP220 in a dose-dependent manner. Moreover, we demonstrate that TRAP220 potentiates NOR-1-mediated transactivation, and interacts with the NR4A1-3 subgroup in an AF-1-dependent manner in a cellular context. The region of TRAP220 that mediated 6-MP activation and NR4A interaction was delimited to amino acids 1-800, and operates independently of the critical PKC and PKA phosphorylation sites. Interestingly, TRAP220 expression does not increase the relative induction by 6-MP, however the absolute level of NOR-1-mediated trans-activation is increased. This study demonstrates that 6-MP modulates the activity of the NR4A subgroup, and the coactivator TRAP220.