Asymmetric Form Research Articles

Molecular dynamics simulations of transitions for ECD epidermal growth factor receptors show key differences between human and drosophila forms of the receptors

Recent X-ray structural work on the Drosophila epidermal growth factor receptor (EFGR) has suggested an asymmetric dimer that rationalizes binding affinity measurements that go back decades (Alvarado et al., Cell 2010;142:568-579; Dawson et al., Structure 2007;15:942-954; Lemmon et al., Embo J 1997;16:281-294; Mattoon et al., Proc Natl Acad Sci USA 2004;101:923-928; Mayawala et al., Febs Lett 2005;579:3043-3047; Ozcan et al., Proc Natl Acad Sci USA 2006;103:5735-5740). This type of asymmetric structure has not been seen for the human EGF receptor family and it may or may not be important for function in that realm. We hypothesize that conformational changes in the Drosophila system have been optimized for the transition, whereas the barrier for the same transition is much higher in the human forms. To address our hypothesis we perform dynamic importance sampling (DIMS) (Perilla et al., J Comput Chem 2010;32:196-209) for barrier crossing transitions in both Drosophila and human EFGRs. For each set of transitions, we work from the hypothesis, based on results from the AdK system, that salt-bridge pairs making and breaking connections are central to the conformational change. To evaluate the effectiveness of the salt-bridges as drivers for the conformational change, we use the effective transfer entropy based on stable state MD calculations (Kamberaj and Der Vaart, Biophys J 2009;97:1747-1755) to define a reduced subset of degrees of freedom that seem to be important for driving the transition (Perilla and Woolf, J Chem Phys 2012;136:164101). Our results suggest that salt-bridge making and breaking is not the dominant factor in driving the symmetric to asymmetric transition, but that instead it is a result of more concerted and correlated functional motions within a subset of the dimer structures. Furthermore, the analysis suggests that the set of residues involved in the transitions from the Drosophila relative to the human forms differs and that this difference in substate distributions relates to why the asymmetric form may be more common to Drosophila than to the human forms. We close with a discussion about the residues that may be changed in the human and the Drosophila forms to potentially shift the kinetics of the symmetric to asymmetric transition.

Первичная гипертрофическая кардиомиопатия у детей

В статье представлены современные сведения об этиологии, патофизиологии, основных клинических признаках, методах обследования, лечения и наблюдения детей с первичной гипертрофической кардиомиопатией. Описано собственное клиническое наблюдение асимметричной формы гипертрофической кардиомиопатии с невыраженной обструкцией выводного тракта левого желудочка у пациента 13 лет. Особенностями данного случая были отягощенный семейный анамнез по сердечно-сосудистой патологии по линии отца, длительное бессимптомное течение заболевания, синкопальное состояние у ребенка, которое послужило поводом к углубленному диагностическому поиску и установлению диагноза. Поздняя диагностика заболевания привела к его прогрессированию, ухудшению прогноза для жизни пациента вследствие высокого риска внезапной сердечной смерти, что в катамнезе и имело место у данного мальчика.

OP-028 TRANSCORONARY SEPTAL ALCOHOL ABLATION IN OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY WITH HIGH PRESSURE GRADIENT: UNICENTER SHORT TERM RESULTS

left ventricular wall was noted, where in 28 patients hypertrophy was asymmetric while 14 had concentric hypertrophy of left ventricle. Left ventricular ejection fraction was depressed in the 21 patients, all with signs of heart failure. Patients in cardiac failure received various combinations of diuretics, B-blockers, ACE inhibitors and aspirin. Surgical intervention was not performed to none of them, despite of clinical and echocardiographic indications. Death occurred in 8 patients, in 4 of them shortly after admission, 3 left Kosovo against medical advice and continued examination in Italy and Germany, and the remaining 32 were followed-up for a mean 42 months, with a range from 5 to 115 months. Recovery was noted in 14 patients but still requiring anti-failure medications. Slightly over two-fifths died. Of those with asymmetric form, 45% died, in half of those presenting in infancy, and 89% of those who presented with signs of cardiac failure. Conclusion: Hypertrophic cardiomyopathy manifested often in severe form in our patients, and the response to standard anti-failure therapy was unsatisfactory. The goals of therapy in HCM are symptoms control and prolongation of survival. In summary, randomized clinical trials would be quite valuable to help define optimal care of children with hypertrophic cardiomyopathy. Significant challenges exist, such as various medical combinations in therapy, surgical intervention and heart transplantation.

The Jacobin Republic and Language Rights. Ethnolinguistic Mobilizations in France

France is usually considered as the symbol of cultural unification and homogeneity. It is commonly (and, in part, correctly) assumed that the process of political centralization in France profoundly shaped the language preferences of citizens. Nevertheless, sociological surveys reveal a tension between the Jacobin Republican drive for uniformity and a more fine-grained empirical reality in the field of the governance of regional languages. Through the comparison of three case studies (Corsica, Brittany and Picardy), this paper reveals that the defence of lesser-used languages and regional dialects has produced an asymmetrical form of ethnolinguistic mobilization by social movements and political parties, which has been more or less credible depending on processes of institutionalization, actor-accommodation and the official recognition of the lesser-used language in question. Through focusing on the specific case of regional languages, the article leads us to examine not only the recent transformations of the French language policy model, but also to reconsider the nature of the contemporary French state.

Nonlinear oscillations of gas in a closed tube under shock-free wave conditions

In this paper, the results of studying peculiarities of longitudinal nonlinear oscillations of homogeneous gas (air) in closed tubes under shock-free wave conditions near the basic natural frequency are presented. At the resonance frequency, a continuous wave of gas pressure in time has the asymmetric form: time of compression is less than that of rarefaction. The resonance frequency being observed has in this case a lesser value than that calculated by the linear theory and coincides with the frequency determined by using the nonlinear theory (with regard to losses). Also shown is an adequate agreement between the theoretically obtained data on swing of gas pressure oscillations and the experimental results.

Synaptic behavior and STDP of asymmetric nanoscale memristors in biohybrid systems

We fabricate and characterize asymmetric memristors which show a very strong single-sided hysteresis. When biased in one direction there is hysteresis and in the opposite direction there is a lack of hysteresis. We demonstrate that this apparent lack is actually hysteresis on a much faster time-scale. We further demonstrate that this form of asymmetric behavior correlates very well to the asymmetric structure and function of an actual synapse. The asymmetric memristor device presented here is necessary to correctly implement spike-timing-dependent-plasticity STDP in mixed memristor/neuron hybrid systems as an artificial synapse. These devices show the required characteristics for implementing the asymmetric form of long-term potentiation (LTP) and long-term depression (LTD) of a synapse between two neurons, where symmetric memristor devices do not. Signals from a presynaptic neuron are sent via its axon across the synapse to the dendrite of a postsynaptic neuron. Postsynaptic neuron signals sent to subsequent neurons have an influence on the strength of any further presynaptic neuron signals received by the postsynaptic neuron across the synapse. These signals are grouped into spike triplets within the framework of STDP and, as we experimentally show here, can be implemented with asymmetric memristors, not standard symmetric memristors.

Two-photon absorption spectra of a near-infrared 2-azaazulene polymethine dye: solvation and ground-state symmetry breaking

Polymethine dyes (PDs) with absorption bands in the near-infrared region undergo symmetry breaking in polar solvents. To investigate how symmetry breaking affects nonlinear optical responses of PDs, an extensive and challenging experimental characterization of a cationic 2-azaazulene polymethine dye, including linear absorption, fluorescence, two-photon absorption and excited-state absorption, has been performed in two solvents with different polarity. Based on this extensive set of experimental data, a three-electronic-state model, accounting for the coupling of electronic degrees of freedom to molecular vibrations and polar solvation, has been reliably parameterized and validated for this dye, fully rationalizing optical spectra in terms of spectral position, intensities and bandshapes. In low-polarity solvents where the dye is mainly in its symmetric form, a nominally forbidden two-photon absorption band is observed, due to a vibronic activation mechanism. Inhomogeneous broadening plays a major role in polar solvents: absorption spectra represent the weighted sum of contributions from states with a variable amount of symmetry breaking, leading to a complex evolution of linear and nonlinear optical spectra with solvent polarity. In more polar solvents, the dominant role of the asymmetric form leads to the activation of two-photon absorption as a result of the symmetry lowering. The subtle interplay between the two mechanisms for two-photon absorption activation, vibronic coupling and polar solvation, can be fully accounted for within the proposed microscopic model allowing a detailed interpretation of the optical spectra of PDs.

Asymmetric Form of Redox Shuttle Based on 1,4-Di-tert-butyl-2,5-dimethoxybenzene

The concept of redox shuttles (RS) has been applied in lithium ion batteries for overcharge protection as well as catholytes for non-aqueous flow batteries. Stable RS compounds typically have a symmetric molecular structure with C2 v symmetry incorporating two identical alkoxy groups. We have successfully broken this symmetry by incorporating two non-identical alkoxy groups (-OMe and –OCH2CF3) on the parent 2,5-di-tert-butylbenzene structure. This asymmetric form of RS compound can survive more than 70 overcharge cycles for more than 1000 hours (100% overcharge, C/5 rate) at relatively low concentration of 0.1 M RS in 1.2M LiPF6 EC/EMC electrolyte for LiFePO4 /Li4Ti5O12 cell.

Comparing sensitivity to facial asymmetry and facial identity.

Bilateral symmetry is a facial feature that plays an important role in the aesthetic judgments of faces. The extent to which symmetry contributes to the identification of faces is less clear. We investigated the relationship between facial asymmetry and identity using synthetic face stimuli where the geometric identity of the face can be precisely controlled. Thresholds for all observers were 2 times lower for discriminating facial asymmetry than they were for discriminating facial identity. The advantage for discriminating asymmetrical forms was not observed using nonface shape stimuli, suggesting this advantage is face-specific. Moreover, asymmetry thresholds were not affected when faces were either inverted or constructed about a nonmean face. These results, taken together, suggest that facial asymmetry is a characteristic that we are exquisitely sensitive to, and that may not contribute to face identification. This conclusion is consistent with neuroimaging evidence that suggests that face symmetry and face identity are processed by different neural mechanisms.

Transatrial Antegrade Approach for Double Mitral and Tricuspid “Valve-in-Ring” Implantation

Within the last 5 years, the number of transcatheter aortic valve implantation (TAVI) procedures has increased continuously and, in parallel, the indications for TAVI have expanded (eg, failing surgical valves and rings). Furthermore, alternative TAVI access routes such as transaxillary and transaortic have been applied successfully. We report on, to our knowledge, the first-in-human case of a combined off-pump antegrade transatrial implantation of a transcatheter valve within a mitral and tricuspid annuloplasty ring through an anterolateral minithoracotomy. The patient showed severe mitral valve and tricuspid valve stenosis and regurgitation 15 years after mitral valve repair and 7 years after aortic valve replacement and tricuspid valve repair.

Combining block-coded modulation codes and improved constellation extended schemes to reduce peak-to-average power ratio in orthogonal frequency-division multiplexing systems

Orthogonal frequency-division multiplexing (OFDM) has been recommended as the standard for numerous wireless transmission systems. However, OFDM still has deficiencies that must be improved, such as a high peak-to-average power ratio (PAPR) occurring in the transmission signal. A constellation extended scheme (CES) is one technology for reducing high PAPR. The PAPR performance of the CES is directly correlated to the amount of candidate signals, high PAPR in OFDM systems will be significantly reduced as the candidate signals increase. However, because calculating the PAPR values of candidate signals requires more inverse fast Fourier transform operations, the CES hardware circuit is difficult to achieve. Therefore this study combines the CES, partial transmit sequences (PTSs) and block-coded modulation (BCM) codes to propose a BCM–CES–PTS technology, which simultaneously improves the high computation of the CES, the necessary side information delivered in PTS and the lack of error correction capabilities in the transmitted signal itself, applying this to a 16-QAM modulation OFDM system. In addition, this study proposes two structures of the CES by arranging the extended constellation points in symmetrical and asymmetrical forms, called S-BCM–CES–PTS and AS-BCM–CES–PTS, respectively. The generator matrices of the two structures were proposed to simplify the division of the circuit into sub-blocks.

Effects of Feedback Respiratory Exercise and Diaphragm Respiratory Exercise on the Pulmonary Functions of Chronic Stroke Patients

Stroke patients show respiratory insufficiency dueto limited physical activity(1). In particular, thepatients’ cardiopulmonary functions are directly andindirectly affected due to decreased movement of thechest wall and electrical activity of the pareticside(2). Furthermore, the respiratory muscles,including the diaphragm, are paralyzed so that thelung and the thorax cannot be sufficiently dilated. Ifthis condition persists, the thoracic tissues may beshortened, and the thoracic muscles may undergofibrosis to reduce the compliance of the thorax. Thisin turn causes various respiratory system complica-tions, such as atelectasis, changes in muscle force,which may directly and/or indirectly obstruct theperformance of daily living activities, and asymmet-rical postures or movement forms, which may ham-per the stability of motion thereby making the per-formance of fine extremity functions difficult(3).This muscle force weakening appears not only inextremity muscles but also in the muscles distributedin the trunk, affecting both the major and accessoryrespiratory muscles(4). In particular, respiratorymuscle weakening affects dyspnea and the ability toperform exercise so that therapeutic interventions,such as ventilatory muscle training, are required toreinforce respiratory muscle functions in order torelieve gasping respiration and improve exercise tol-erance(5). Therefore, to solve the problems of declin-ing efficiency in patients’ breathing and changes inpatients’ respiratory mechanisms, chest wall dilationand ventilation and lung capacity and volume needto be appropriately maintained(6), after assessing

Symbiotic two-component gap solitons

We consider a two-component one-dimensional model of gap solitons (GSs), which is based on two nonlinear Schrödinger equations, coupled by repulsive XPM (cross-phase-modulation) terms, in the absence of the SPM (self-phase-modulation) nonlinearity. The equations include a periodic potential acting on both components, thus giving rise to GSs of the "symbiotic" type, which exist solely due to the repulsive interaction between the two components. The model may be implemented for "holographic solitons" in optics, and in binary bosonic or fermionic gases trapped in the optical lattice. Fundamental symbiotic GSs are constructed, and their stability is investigated, in the first two finite bandgaps of the underlying spectrum. Symmetric solitons are destabilized, including their entire family in the second bandgap, by symmetry-breaking perturbations above a critical value of the total power. Asymmetric solitons of intra-gap and inter-gap types are studied too, with the propagation constants of the two components falling into the same or different bandgaps, respectively. The increase of the asymmetry between the components leads to shrinkage of the stability areas of the GSs. Inter-gap GSs are stable only in a strongly asymmetric form, in which the first-bandgap component is a dominating one. Intra-gap solitons are unstable in the second bandgap. Unstable two-component GSs are transformed into persistent breathers. In addition to systematic numerical considerations, analytical results are obtained by means of an extended ("tailed") Thomas-Fermi approximation (TFA).

An atomic model calculation of exchange anisotropy and uncompensated spin element in antiferromagnetic layer: An effect of exchange coupling with various ferromagnetic materials

An atomic model of the direct exchange coupling in an antiferromagnetic (AF) and ferromagnetic (FM) bilayer has been investigated. Exchange anisotropy is achieved by different mechanisms in the body-centred-cubic and face-centred-cubic FM layers. For the former, the formation of an AF domain wall directly causes the exchange anisotropy. For the latter, a cooperative effect in the AF domain wall and the asymmetric form of the uncompensated AF spins produces the exchange anisotropy.

Interaction of inhibition and triplets of excitatory spikes modulates the NMDA-R-mediated synaptic plasticity in a computational model of spike timing-dependent plasticity

Spike timing-dependent plasticity (STDP) experiments have shown that a synapse is strengthened when a presynaptic spike precedes a postsynaptic one and depressed vice versa. The canonical form of STDP has been shown to have an asymmetric shape with the peak long-term potentiation at +6 ms and the peak long-term depression at -5 ms. Experiments in hippocampal cultures with more complex stimuli such as triplets (one presynaptic spike combined with two postsynaptic spikes or one postsynaptic spike with two presynaptic spikes) have shown that pre-post-pre spike triplets result in no change in synaptic strength, whereas post-pre-post spike triplets lead to significant potentiation. The sign and magnitude of STDP have also been experimentally hypothesized to be modulated by inhibition. Recently, a computational study showed that the asymmetrical form of STDP in the CA1 pyramidal cell dendrite when two spikes interact switches to a symmetrical one in the presence of inhibition under certain conditions. In the present study, I investigate computationally how inhibition modulates STDP in the CA1 pyramidal neuron dendrite when it is driven by triplets. The model uses calcium as the postsynaptic signaling agent for STDP and is shown to be consistent with the experimental triplet observations in the absence of inhibition: simulated pre-post-pre spike triplets result in no change in synaptic strength, whereas simulated post-pre-post spike triplets lead to significant potentiation. When inhibition is bounded by the onset and offset of the triplet stimulation, then the strength of the synapse is decreased as the strength of inhibition increases. When inhibition arrives either few milliseconds before or at the onset of the last spike in the pre-post-pre triplet stimulation, then the synapse is potentiated. Variability in the frequency of inhibition (50 vs. 100 Hz) produces no change in synaptic strength. Finally, a 5% variation in model's calcium parameters (calcium thresholds) proves that the model's performance is robust.

Application of matrices and coordinate transformations to analysis of vibrations of block and wall machine foundations of asymmetric form

A method is proposed for analysis of vibrations of foundations of complex form, making it possible to employ more complex technical solutions, including the reconstruction of active establishments, or, when necessary, their strengthening. The results are incorporated in the Construction Rules and Regulations “Dynamically loaded machine foundations,” which are presently being implemented.

Internal electric fields and color shift in Cr3+-based gemstones

Seeking to better understand the origin of the different colors of emerald and ruby, both ab initio periodic and cluster calculations have been carried out. The calculations reproduce the interatomic distances measured for pure Be${}_{3}$Si${}_{6}$Al${}_{2}$O${}_{18}$ and Al${}_{2}$O${}_{3}$ as well as the Cr${}^{3+}$$\ensuremath{-}{\mathrm{O}}^{2\ensuremath{-}}$ distances in emerald and ruby. The mean Cr${}^{3+}$$\ensuremath{-}{\mathrm{O}}^{2\ensuremath{-}}$ distance for Be${}_{3}$Si${}_{6}$Al${}_{2}$O${}_{18}$:Cr${}^{3+}$ and Al${}_{2}$O${}_{3}$:Cr${}^{3+}$ is found to be practically equal to 1.97 \AA{}, in agreement with recent experimental values. The present calculations confirm that the variations of optical properties due to Cr${}^{3+}$ impurities along the series of ionic oxides can be understood merely through the CrO${}_{6}{}^{9\ensuremath{-}}$ unit but subject to the electric field due to the rest of the lattice ions. As a salient feature it is proved that changes in electronic density and covalency due to the internal field are not the cause of the color shift. Therefore, the red color of ruby is not due to the polarization of the electronic cloud around chromium as a result of the C${}_{3}$ local symmetry. The present study also demonstrates that the variation of the ligand field splitting parameter, 10Dq, induced by the internal electric field comes mainly from the contributions of first shells of ions around the CrO${}_{6}{}^{9\ensuremath{-}}$ unit. As a consequence, 10Dq in emerald is not influenced by the internal field, as the contribution from Be${}^{2+}$ first neighbors is practically compensated by that of Si${}^{4+}$ second neighbors. In contrast, in ruby the ${t}_{2g}$ levels are shifted by the internal field 0.24 eV more than the ${e}_{g}$ ones, so explaining the color shift in this gemstone in comparison with emerald. This result is shown to arise partially from the asymmetric form of the internal electrostatic potential along the ${C}_{3}$ axis in Al${}_{2}$O${}_{3}$.

Bursts shape the NMDA-R mediated spike timing dependent plasticity curve: role of burst interspike interval and GABAergic inhibition.

Spike timing dependent plasticity (STDP) is a synaptic learning rule where the relative timing between the presynaptic and postsynaptic action potentials determines the sign and strength of synaptic plasticity. In its basic form STDP has an asymmetric form which incorporates both persistent increases and persistent decreases in synaptic strength. The basic form of STDP, however, is not a fixed property and depends on the dendritic location. An asymmetric curve is observed in the distal dendrites, whereas a symmetrical one is observed in the proximal ones. A recent computational study has shown that the transition from the asymmetry to symmetry is due to inhibition under certain conditions. Synapses have also been observed to be unreliable at generating plasticity when excitatory postsynaptic potentials and single spikes are paired at low frequencies. Bursts of spikes, however, are reliably signaled because transmitter release is facilitated. This article presents a two-compartment model of the CA1 pyramidal cell. The model is neurophysiologically plausible with its dynamics resulting from the interplay of many ionic and synaptic currents. Plasticity is measured by a deterministic Ca(2+) dynamics model which measures the instantaneous calcium level and its time course in the dendrite and change the strength of the synapse accordingly. The model is validated to match the asymmetrical form of STDP from the pairing of a presynaptic (dendritic) and postsynaptic (somatic) spikes as observed experimentally. With the parameter set unchanged the model investigates how pairing of bursts with single spikes and bursts in the presence or absence of inhibition shapes the STDP curve. The model predicts that inhibition strength and frequency are not the only factors of the asymmetry-to-symmetry switch of the STDP curve. Burst interspike interval is another factor. This study is an important first step towards understanding how STDP is affected under natural firing patterns in vivo.

Apparitions of neoliberalism: revisiting ‘Jungle law breaks out’

The authors revisit their paper, ‘Jungle law breaks out: neoliberalism and global‐local disorder’, published by Area in 1994, commenting on the theoretical and political context of that time and on the subsequent course of debates around neoliberalism. Focusing on the Thatcherite strain of neoliberalism as a manifestation of post‐Keynesian crisis politics, and along with its associated strategies of deregulatory devolution, the paper called particular attention to the project's reactive moment and to its distinctive mode of scalar politics. Subsequent experience has underlined the stubbornly adaptive character of the neoliberalisation process, which nevertheless continues to be animated by crises (of a contingent and conjunctural nature), while propagating yet more asymmetrical forms of regulatory rescaling. It might be said that a kind of jungle law, in this sense, continues to hold sway.

Parametric study of a low wake-wash inland waterways catamaran

The wake wash from passing ships can cause environmental damage. The wake wash is an important issue for naval architects and shipbuilders in concentrating on more environmentally friendly designs. This paper presents results of a parametric study of catamaran hull form to obtain low wake wash hull form configurations or low speed inland waterway boats. The study uses a Computational Fluid Dynamics (CFD) simulation, and model experiments were carried out for validation of the CFD software set-up. The study concentrates on the asymmetric catamaran hull form. The investigation is conducted on two configurations of hull form; Flat Side Inward (FSI) and Flat Side Outward (FSO) configurations. The investigation is conducted on a hull form with a Length to Beam (L/B) ratio of 12.2, 15.2 and 18.3 and a Separation to Length (S/L) ratio of 0.2, 0.3 and 0.4. The results based on wave height criteria at various longitudinal cuts have shown that the FSO configuration has a lower wake wash compared with the FSI configuration. Considering L/B and S/L ratios, hull forms with a larger separation or higher L/B ratios produce lower wave heights.