Neck pounding during sinus rhythm: a new clinical manifestation of dual atrioventricular nodal pathways

Objective To determine the clinical and electrophysiological characteristics of patients with paroxysmal palpitations and neck pounding during sinus rhythm. Methods Clinical, electrocardiographic, and electrophysiological characteristics of six patients with paroxysmal palpitations and neck pounding during sinus rhythm were studied in basal conditions and when symptomatic. Response to treatment was observed. Results Baseline ECGs were normal (four patients) or had first degree atrioventricular block with intermittent PR shortening. During symptoms, narrow QRS rhythms were seen without visible P waves (three patients) or with P waves partially hidden in the QRS complex (three patients). Dual atrioventricular nodal pathways were found in all five patients who had electrophysiological studies. In these patients the slow pathway conduction time was long enough (mean (SD), 425 (121)¿ms) for ventricular activation after slow pathway conduction during sinus rhythm to coincide with the next atrial depolarisation, causing neck pounding during exercise (four patients) or at rest (two patients). Tachycardia was not induced in any patient. Medical treatment aggravated symptoms in three patients. A pacemaker was successfully used in two. Conclusions Neck pounding during sinus rhythm is a clinical manifestation of dual atrioventricular nodal pathways. Medical treatment may aggravate symptoms but a pacemaker may offer definitive relief.

The role of dynamical polarization of the ligand-to-metal charge transfer excitations in the ab initio determination of effective exchange parameters

The role of the bridging ligand on the effective Heisenberg coupling parameters is analyzed in detail. This analysis strongly suggests that the ligand-to-metal charge transfer excitations are responsible for a large part of the final value of the magnetic coupling constant. This permits us to suggest a variant of the difference dedicated configuration interaction (DDCI) method, presently one of the most accurate and reliable for the evaluation of magnetic effective interactions. This method treats the bridging ligand orbitals mediating the interaction at the same level than the magnetic orbitals and preserves the high quality of the DDCI results while being much less computationally demanding. The numerical accuracy of the new approach is illustrated on various systems with one or two magnetic electrons per magnetic center. The fact that accurate results can be obtained using a rather reduced configuration interaction space opens the possibility to study more complex systems with many magnetic centers and/or many electrons per center.

Self construction, cognitive conflicts and polarization in bulimia nervosa

This study explores the cognitive structures, understood as construct systems, of patients suffering from bulimia nervosa (BN). Previous studies investigated the construct systems of disordered eaters suggesting that they had a higher distance between their construction of the self and the «ideal self», and also more rigidity. In addition to these aspects, this study explored the presence of implicative dilemmas (ID). Thirty two women who met criteria for BN and were treated in a specialized center were compared to a non clinical group composed by 32 women matched by age. All participants were assessed using Repertory Grid Technique (RGT). In BN patients it was more common (71.9%) to find IDs than in controls (18.8%). They also showed higher polarization and higher self-ideal discrepancies (even more for those with a long history of BN). The measures provided by the RGT can be useful for the assessment of self-construction and cognitive conflicts in BN patients and to appreciate their role in this disorder. In addition, this technique could be helpful for clinicians to explore the patient"s constructs system, and specially to identify IDs that could be maintaining the symptoms or hindering change in order to focus on them to facilitate improvement.

Polychlorinated trityl radicals for dynamic nuclear polarization: the role of chlorine nuclei

Polychlorinated trityl radicals bearing carboxylate substituents are water soluble persistent radicals that can be used for dynamic nuclear polarization. In contrast to other trityl radicals, the polarization mechanism differs from the classical solid effect. DFT calculations performed to rationalize this behaviour support the hypothesis that polarization is transferred from the unpaired electron to chlorine nuclei and from these to carbon by spin diffusion. The marked differences observed between neutral and anionic forms of the radical will be discussed.

Spatial Polarization of the Ecological Footprint distribution

The international allocation of natural resources is determined, not by any ethical or ecological criteria, but by the dominance of market mechanisms. From a core-periphery perspective, this allocation may even be driven by historically determined structural patterns, with a core group of countries whose consumption appropriates most available natural resources, and another group, having low natural resource consumption, which plays a peripheral role. This article consists of an empirical distributional analysis of natural resource consumption (as measured by Ecological Footprints) whose purpose is to assess the extent to which the distribution of consumption responds to polarization (as opposed to mere inequality). To assess this, we estimate and decompose different polarization indices for a balanced sample of 119 countries over the period 1961 to 2007. Our results points toward a polarized distribution which is consistent with a core-periphery framework.

Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates

Notwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer"s disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multi-target anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.

Spatial polarization of the ecological footprint distribution

The international allocation of natural resources is determined, not by any ethical or ecological criteria, but by the dominance of market mechanisms. From a core-periphery perspective, this allocation may even be driven by historically determined structural patterns, with a core group of countries whose consumption appropriates most available natural resources, and another group, having low natural resource consumption, which plays a peripheral role. This article consists of an empirical distributional analysis of natural resource consumption (as measured by Ecological Footprints) whose purpose is to assess the extent to which the distribution of consumption responds to polarization (as opposed to mere inequality). To assess this, we estimate and decompose different polarization indices for a balanced sample of 119 countries over the period 1961 to 2007. Our results points toward a polarized distribution which is consistent with a core-periphery framework. Keywords: Polarization, Core-Periphery, Ecological Footprint

Free Open Source Software and Dual-Use: Loophole or Dissent?

The Free Open Source Software (FOSS) seem far from the military field but in some cases, some technologies normally used for civilian purposes may have military applications. These products and technologies are called dual-use. Can we manage to combine FOSS and dual-use products? On one hand, we have to admit that this kind of association exists - dual-use software can be FOSS and many examples demonstrate this duality - but on the other hand, dual-use software available under free licenses lead us to ask many questions. For example, the dual-use export control laws aimed at stemming the proliferation of weapons of mass destruction. Dual-use export in United States (ITAR) and Europe (regulation 428/2009) implies as a consequence the prohibition or regulation of software exportation, involving the closing of source code. Therefore, the issues of exported softwares released under free licenses arises. If software are dual-use goods and serve for military purposes, they may represent a danger. By the rights granted to licenses to run, study, redistribute and distribute modified versions of the software, anyone can access the free dual-use software. So, the licenses themselves are not at the origin of the risk, it is actually linked to the facilitated access to source codes. Seen from this point of view, it goes against the dual-use regulation which allows states to control these technologies exportation. For this analysis, we will discuss about various legal questions and draft answers from either licenses or public policies in this respect.

An activator/repressor dual system allows tight tetracycline-regulated gene expression in budding yeast

We have developed an activator/repressor expression system for budding yeast in which tetracyclines control in opposite ways the ability of tetR-based activator and repressor molecules to bind tetO promoters. This combination allows tight expression of tetO-driven genes, both in a direct (tetracycline-repressible) and reverse (tetracycline-inducible) dual system. Ssn6 and Tup1, that are components of a general repressor complex in yeast, have been tested for their repressing properties in the dual system, using lacZ and CLN2 as reporter genes. Ssn6 gives better results and allows complete switching-off of the regulated genes, although increasing the levels of the Tup1-based repressor by expressing it from a stronger promoter improves repressing efficiency of the latter. Effector-mediated shifts between expression and non-expression conditions are rapid. The dual system here described may be useful for the functional analysis of essential genes whose conditional expression can be tightly controlled by tetracyclines.

The membrane-permeable calmodulin inhibitors (W-7/W-13) bind to membranes changing the electrostatic surface potential. Dual effect of W-13 on EGFR activation

Membrane-permeable calmodulin inhibitors, such as the napthalenesulfonamide derivatives W-7/W-13, trifluoperazine, and calmidazolium, are used widely to investigate the role of calcium/calmodulin (Ca2+/CaM) in living cells. If two chemically different inhibitors (e.g. W-7 and trifluoperazine) produce similar effects, investigators often assume the effects are due to CaM inhibition. Zeta potential measurements, however, show that these amphipathic weak bases bind to phospholipid vesicles at the same concentrations as they inhibit Ca 2 /CaM; this suggests that they also bind to the inner leaflet of the plasma membrane, reducing its negative electrostatic surface potential. This change will cause electrostatically bound clusters of basic residues on peripheral (e.g. Src and K-Ras4B) and integral (e.g. epidermal growth factor receptor (EGFR)) proteins to translocate from the membrane to the cytoplasm. We measured inhibitor-mediated translocation of a simple basic peptide corresponding to the calmodulin-binding juxtamembrane region of the EGFR on model membranes; W-7/W-13 causes translocation of this peptide from membrane to solution, suggesting that caution must be exercised when interpreting the results obtained with these inhibitors in living cells. We present evidence that they exert dual effects on autophosphorylation of EGFR;W-13 inhibits epidermal growth factordependent EGFR autophosphorylation under different experimental conditions, but in the absence of epidermal growth factor, W-13 stimulates autophosphorylation of the receptor in four different cell types. Our interpretation is that the former effect is due toW-13inhibition of Ca 2 /CaM, but thelatter results could be due to binding of W-13 to the plasma membrane.

Health-related quality of life in patients with dual diagnosis: clinical correlates

Background: Although the studies published so far have found an affectation in the Health Related Quality of Life (HRQOL) in both psychiatric and substance use dependence disorders, very few studies have applied HRQOL as an assessment measure in patients suffering both comorbid conditions, or Dual Diagnosis. The aim of the current study was to assess HRQOL in a group of patients with Dual Diagnosis compared to two other non-comorbid groups and to determine what clinical factors are related to HRQOL. Methods: Cross-sectional assessment of three experimental groups was made through the Short Form 36 Item Health Survey (SF-36). The sample consisted of a group with Dual Diagnosis (DD; N=35), one with Severe Mental Illness alone (SMI; N=35) and another one with Substance Use Dependence alone (SUD; N=35). The sample was composed only by males. To assess the clinical correlates of SF-36 HRQOL, lineal regression analyses were carried out. Results: The DD group showed lower scores in most of the subscales, and in the mental health domain. The group with SUD showed in general a better state in the HRQOL while the group with SMI held an intermediate position with respect to the other two groups. Daily medication, suicidal attempts and daily number of coffees were significantly associated to HRQOL, especially in the DD group. Conclusions: The DD group showed lower self-reported mental health quality of life. Assessment of HRQOL in dual patients allows to identify specific needs in this population, and may help to establish therapeutic goals to improve interventions.

Counter-propagating dual-trap optical tweezers based on linear momentum conservation

We present a dual-trap optical tweezers setup which directly measures forces using linear momentum conservation. The setup uses a counter-propagating geometry, which allows momentum measurement on each beam separately. The experimental advantages of this setup include low drift due to all-optical manipulation, and a robust calibration (independent of the features of the trapped object or buffer medium) due to the force measurement method. Although this design does not attain the high-resolution of some co-propagating setups, we show that it can be used to perform different single molecule measurements: fluctuation-based molecular stiffness characterization at different forces and hopping experiments on molecular hairpins. Remarkably, in our setup it is possible to manipulate very short tethers (such as molecular hairpins with short handles) down to the limit where beads are almost in contact. The setup is used to illustrate a novel method for measuring the stiffness of optical traps and tethers on the basis of equilibrium force fluctuations, i.e., without the need of measuring the force vs molecular extension curve. This method is of general interest for dual trap optical tweezers setups and can be extended to setups which do not directly measure forces.

Force Spectroscopy with Dual-Trap Optical Tweezers: Molecular Stiffness Measurements and Coupled Fluctuations Analysis

ABSTRACT Dual-trap optical tweezers are often used in high-resolution measurements in single-molecule biophysics. Such measurements can be hindered by the presence of extraneous noise sources, the most prominent of which is the coupling of fluctuations along different spatial directions, which may affect any optical tweezers setup. In this article, we analyze, both from the theoretical and the experimental points of view, the most common source for these couplings in dual-trap optical-tweezers setups: the misalignment of traps and tether. We give criteria to distinguish different kinds of misalignment, to estimate their quantitative relevance and to include them in the data analysis. The experimental data is obtained in a, to our knowledge, novel dual-trap optical-tweezers setup that directly measures forces. In the case in which misalignment is negligible, we provide a method to measure the stiffness of traps and tether based on variance analysis. This method can be seen as a calibration technique valid beyond the linear trap region. Our analysis is then employed to measure the persistence length of dsDNA tethers of three different lengths spanning two orders of magnitude. The effective persistence length of such tethers is shown to decrease with the contour length, in accordance with previous studies.

Mueller matrix microscope with a dual continuous rotating compensator setup and digital demodulation

In this paper we describe a new Mueller matrix (MM) microscope that generalizes and makes quantitative the polarized light microscopy technique. In this instrument all the elements of the MU are simultaneously determined from the analysis in the frequency domain of the time-dependent intensity of the light beam at every pixel of the camera. The variations in intensity are created by the two compensators continuously rotating at different angular frequencies. A typical measurement is completed in a little over one minute and it can be applied to any visible wavelength. Some examples are presented to demonstrate the capabilities of the instrument.

Dual role of LldR in regulation of the lldPRD operon, involved in l-Lactate metabolism in Escherichia coli.

The lldPRD operon of Escherichia coli, involved in L-lactate metabolism, is induced by growth in this compound. We experimentally identified that this system is transcribed from a single promoter with an initiation site located 110 nucleotides upstream of the ATG start codon. On the basis of computational data, it had been proposed that LldR and its homologue PdhR act as regulators of the lldPRD operon. Nevertheless, no experimental data on the function of these regulators have been reported so far. Here we show that induction of an lldP-lacZ fusion by L-lactate is lost in an lldR mutant, indicating the role of LldR in this induction. Expression analysis of this construct in a pdhR mutant ruled out the participation of PdhR in the control of lldPRD. Gel shift experiments showed that LldR binds to two operator sites, O1 (positions 105 to 89) and O2 (positions 22 to 38), with O1 being filled at a lower concentration of LldR. L-Lactate induced a conformational change in LldR that did not modify its DNA binding activity. Mutations in O1 and O2 enhanced the basal transcriptional level. However, only mutations in O1 abolished induction by L-lactate. Mutants with a change in helical phasing between O1 and O2 behaved like O2 mutants. These results were consistent with the hypothesis that LldR has a dual role, acting as a repressor or an activator of lldPRD. We propose that in the absence of L-lactate, LldR binds to both O1 and O2, probably leading to DNA looping and the repression of transcription. Binding of L-lactate to LldR promotes a conformational change that may disrupt the DNA loop, allowing the formation of the transcription open complex.