Human Capital Management in Tourism SMEs from a Cyber-Systemic Approach

Systemic Practice and Action Research - This article presents an approach to the problem that small and medium-sized Mexican lodging enterprises face regarding their ability to adapt to changes in...     

Atom-by-atom analysis of global downhill protein folding

Protein folding is an inherently complex process involving coordination of the intricate networks of weak interactions that stabilize native three-dimensional structures. In the conventional paradigm, simple protein structures are assumed to fold in an all-or-none process that is inaccessible to experiment. Existing experimental methods therefore probe folding mechanisms indirectly. A widely used approach interprets changes in protein stability and/or folding kinetics, induced by engineered mutations, in terms of the structure of the native protein. In addition to limitations in connecting energetics with structure, mutational methods have significant experimental uncertainties and are unable to map complex networks of interactions. In contrast, analytical theory predicts small barriers to folding and the possibility of downhill folding. These theoretical predictions have been confirmed experimentally in recent years, including the observation of global downhill folding. However, a key remaining question is whether downhill folding can indeed lead to the high-resolution analysis of protein folding processes. Here we show, with the use of nuclear magnetic resonance (NMR), that the downhill protein BBL from Escherichia coli unfolds atom by atom starting from a defined three-dimensional structure. Thermal unfolding data on 158 backbone and side-chain protons out of a total of 204 provide a detailed view of the structural events during folding. This view confirms the statistical nature of folding, and exposes the interplay between hydrogen bonding, hydrophobic forces, backbone conformation and side-chain entropy. From the data we also obtain a map of the interaction network in this protein, which reveals the source of folding cooperativity. Our approach can be extended to other proteins with marginal barriers (less than 3RT), providing a new tool for the study of protein folding.     

具有周围组织的动脉脉搏波分析

本文提出在周围结缔组织深处动脉的理论模型。利用土力学原理分析动脉纵向振动,指出动脉纵向振动引起周围结缔组织的位移是以表面波形式传播的,动脉纵向波速是表面波相速度,表面波的存在是动脉纵向振动的必要条件。Lamb波速是本文结论特例。     

A new cellular function for peroxisomes related to oxygen free radicals?

Although in cell biology peroxisomes are still 'young' organelles, it is becoming increasingly clear that they are involved in important cellular functions. Recent results have indicated the presence of the metalloenzyme superoxide dismutase in peroxisomes and the production of superoxide free radicals (O2-) in these oxidative organelles. These findings, together with other experimental evidence, point towards the existence of new roles for peroxisomes in cellular active oxygen metabolism, something that has a potential impact in multiple areas of cell biology, particularly in biochemistry and biomedicine.     

Real-time quantum feedback prepares and stabilizes photon number states

Feedback loops are central to most classical control procedures. A controller compares the signal measured by a sensor (system output) with the target value or set-point. It then adjusts an actuator (system input) to stabilize the signal around the target value. Generalizing this scheme to stabilize a micro-system's quantum state relies on quantum feedback, which must overcome a fundamental difficulty: the sensor measurements cause a random back-action on the system. An optimal compromise uses weak measurements, providing partial information with minimal perturbation. The controller should include the effect of this perturbation in the computation of the actuator's operation, which brings the incrementally perturbed state closer to the target. Although some aspects of this scenario have been experimentally demonstrated for the control of quantum or classical micro-system variables, continuous feedback loop operations that permanently stabilize quantum systems around a target state have not yet been realized. Here we have implemented such a real-time stabilizing quantum feedback scheme following a method inspired by ref. 13. It prepares on demand photon number states (Fock states) of a microwave field in a superconducting cavity, and subsequently reverses the effects of decoherence-induced field quantum jumps. The sensor is a beam of atoms crossing the cavity, which repeatedly performs weak quantum non-demolition measurements of the photon number. The controller is implemented in a real-time computer commanding the actuator, which injects adjusted small classical fields into the cavity between measurements. The microwave field is a quantum oscillator usable as a quantum memory or as a quantum bus swapping information between atoms. Our experiment demonstrates that active control can generate non-classical states of this oscillator and combat their decoherence, and is a significant step towards the implementation of complex quantum information operations.     

Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function

Left ventricular mass (LVM) is a highly heritable trait and an independent risk factor for all-cause mortality. So far, genome-wide association studies have not identified the genetic factors that underlie LVM variation, and the regulatory mechanisms for blood-pressure-independent cardiac hypertrophy remain poorly understood. Unbiased systems genetics approaches in the rat now provide a powerful complementary tool to genome-wide association studies, and we applied integrative genomics to dissect a highly replicated, blood-pressure-independent LVM locus on rat chromosome 3p. Here we identified endonuclease G (Endog), which previously was implicated in apoptosis but not hypertrophy, as the gene at the locus, and we found a loss-of-function mutation in Endog that is associated with increased LVM and impaired cardiac function. Inhibition of Endog in cultured cardiomyocytes resulted in an increase in cell size and hypertrophic biomarkers in the absence of pro-hypertrophic stimulation. Genome-wide network analysis unexpectedly implicated ENDOG in fundamental mitochondrial processes that are unrelated to apoptosis. We showed direct regulation of ENDOG by ERR-α and PGC1α (which are master regulators of mitochondrial and cardiac function), interaction of ENDOG with the mitochondrial genome and ENDOG-mediated regulation of mitochondrial mass. At baseline, the Endog-deleted mouse heart had depleted mitochondria, mitochondrial dysfunction and elevated levels of reactive oxygen species, which were associated with enlarged and steatotic cardiomyocytes. Our study has further established the link between mitochondrial dysfunction, reactive oxygen species and heart disease and has uncovered a role for Endog in maladaptive cardiac hypertrophy.     

Messinian salinity crisis regulated by competing tectonics and erosion at the Gibraltar arc

The Messinian salinity crisis (5.96 to 5.33 million years ago) was caused by reduced water inflow from the Atlantic Ocean to the Mediterranean Sea resulting in widespread salt precipitation and a decrease in Mediterranean sea level of about 1.5 kilometres due to evaporation. The reduced connectivity between the Atlantic and the Mediterranean at the time of the salinity crisis is thought to have resulted from tectonic uplift of the Gibraltar arc seaway and global sea-level changes, both of which control the inflow of water required to compensate for the hydrological deficit of the Mediterranean. However, the different timescales on which tectonic uplift and changes in sea level occur are difficult to reconcile with the long duration of the shallow connection between the Mediterranean and the Atlantic needed to explain the large amount of salt precipitated. Here we use numerical modelling to show that seaway erosion caused by the Atlantic inflow could sustain such a shallow connection between the Atlantic and the Mediterranean by counteracting tectonic uplift. The erosion and uplift rates required are consistent with previous mountain erosion studies, with the present altitude of marine sediments in the Gibraltar arc and with geodynamic models suggesting a lithospheric slab tear underneath the region. The moderate Mediterranean sea-level drawdown during the early stages of the Messinian salinity crisis can be explained by an uplift of a few millimetres per year counteracted by similar rates of erosion due to Atlantic inflow. Our findings suggest that the competition between uplift and erosion can result in harmonic coupling between erosion and the Mediterranean sea level, providing an alternative mechanism for the cyclicity observed in early salt precipitation deposits and calling into question previous ideas regarding the timing of the events that occurred during the Messinian salinity crisis.     

Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells

Human induced pluripotent stem cells (iPSCs) represent a unique opportunity for regenerative medicine because they offer the prospect of generating unlimited quantities of cells for autologous transplantation, with potential application in treatments for a broad range of disorders. However, the use of human iPSCs in the context of genetically inherited human disease will require the correction of disease-causing mutations in a manner that is fully compatible with clinical applications. The methods currently available, such as homologous recombination, lack the necessary efficiency and also leave residual sequences in the targeted genome. Therefore, the development of new approaches to edit the mammalian genome is a prerequisite to delivering the clinical promise of human iPSCs. Here we show that a combination of zinc finger nucleases (ZFNs) and piggyBac technology in human iPSCs can achieve biallelic correction of a point mutation (Glu342Lys) in the α(1)-antitrypsin (A1AT, also known as SERPINA1) gene that is responsible for α(1)-antitrypsin deficiency. Genetic correction of human iPSCs restored the structure and function of A1AT in subsequently derived liver cells in vitro and in vivo. This approach is significantly more efficient than any other gene-targeting technology that is currently available and crucially prevents contamination of the host genome with residual non-human sequences. Our results provide the first proof of principle, to our knowledge, for the potential of combining human iPSCs with genetic correction to generate clinically relevant cells for autologous cell-based therapies.     

A Combinatorial Approach to Assess the Separability of Clusters

Separability of clusters is an issue that arises in many different areas, and is often used in a rather vague and subjective manner. We introduce a combinatorial notion of interiority to derive a global view on separability of a set of entities. We develop this approach further to evaluate the overall separability of a partition in the context of cluster analysis. Our approach captures combinatorial and geometrical aspects of data and provides, in addition to numerical evaluations, graphical representations particularly useful when data are not easily visualized. We illustrate the methodology on some real and simulated datasets.