Use of the free vastus lateralis flap in skull base reconstruction

Free flaps in skull base reconstruction are indicated for providing an effective separation of the intracranial cavity from the oronasal space, for eliminating a dead space, and for the treatment of established wound complications such as dural exposures and cerebrospinal fluid leaks. Seven patients with cranial base defects underwent reconstructions using a free vastus lateralis muscle flap. In two cases, a vastus lateralis flap was raised to incorporate the anterolateral thigh skin as a myocutaneous flap. In four cases, a free flap was indicated for reconstruction following tumor ablation, and in three cases, for the resolution of wound or cerebrospinal fluid leak complications following previous cranial base surgery. All flaps were successful, with no partial failures. In those patients undergoing tumor ablative surgery, the cranial cavity was effectively sealed from the oronasal cavity. Patients with established wound complications following previous cranial base surgery had a complete resolution of their symptoms. This report discusses the suitability of the vastus lateralis flap for skull base reconstruction in terms of the availability of adequate muscle volume to fill dead space, vascularized fascia to augment dural repairs, and the freedom to use skin if required for internal lining or external skin cover. This flap also provides an extremely long pedicle, allows simultaneous flap harvest, and has low donor site morbidity.     

Studies on aromatic compounds: inhibition of calpain I by biphenyl derivatives and peptide-biphenyl hybrids

With the objective to understand structural features responsible for the biological activity, novel nonelectrophilic biphenyl derivatives and peptide-biphenyl hybrids have been synthesized and evaluated as calpain I inhibitors. The preliminary results indicate that the presence of additional aromatic rings (besides the biphenyl system) makes these compounds potent calpain inhibitors with IC50 values in the nanomolar range.     

Synthesis and nematocide activity of S-glycopyranosyl-6,7-diarylthiolumazines

6,7-Diaryl derivatives of mono and di-S-glycopyranosylthiolumazine derivatives 5-8 were prepared to test their nematocide activity. In vitro tests against Caenorhabditis elegans were performed and it was found that monosubstituted derivatives 5-7 showed higher activity than the corresponding unsubstituted 2-thiolumazines 1-3, whilst 2-S,4-S-di-glycopyranosylpteridine derivative 8 was inactive in contrast to unsubstituted derivative 4. In order to check whether the lack of activity of 8 was due to the two bulky substituents of the pteridine nucleus, 2-S,4-S-dimethyl derivative 9 was synthesized and assayed showing also lack of activity. A theoretical study on the stability of the different possible tautomers of compound 4 was carried out in an attempt to explain some, in appearance, anomalous (13)C NMR data of this compound.     

Signatures of diversifying selection and convergence acting on passerine Toll‐like receptor 4 in an evolutionary context

Positive selection acting on Toll‐like receptors (TLRs) has been recently investigated to reveal evolutionary mechanisms of host–pathogen molecular co‐adaptation. Much of this research, however, has focused mainly on the identification of sites predicted to be under positive selection, bringing little insight into the functional differences and similarities among species and a limited understanding of convergent evolution in the innate immune molecules. In this study, we provide evidence of phenotypic variability in the avian TLR4 ligand‐binding region (LBR), the direct interface between host and pathogen molecular structures. We show that 55 passerine species vary substantially in the distribution of electrostatic potential on the surface of the receptor, and based on these distinct patterns, we identified four species clusters. Seven of the 34 evolutionarily nonconservative and positively selected residues correspond topologically to sites previously identified as being important for lipopolysaccharide, lipid IVa or MD‐2 binding. Five of these positions codetermine the identity of the charge clusters. Groups of species that host‐related communities of pathogens were predicted to cluster based on their TLR4 LBR charge. Despite some evidence for convergence among taxa, there were no clear associations between the TLR4 LBR charge distribution and any of the general ecological characteristics compared (migration, latitudinal distribution and diet). Closely related species, however, mostly belonged to the same surface charge cluster indicating that phylogenetic constraints are key determinants shaping TLR4 adaptive evolution. Our results suggest that host innate immune evolution is consistent with Fahrenholz's rule on the cospeciation of hosts and their parasites.     

Energy aware scheduling of deadline-constrained tasks in cloud computing

Energy efficiency is the predominant issue which troubles the modern ICT industry. The ever-increasing ICT innovations and services have exponentially added to the energy demands and this proliferated the urgency of fostering the awareness for development of energy efficiency mechanisms. But for a successful and effective accomplishment of such mechanisms, the support of underlying ICT platform is significant. Eventually, Cloud computing has gained attention and has emerged as a panacea to beat the energy consumption issues. This paper scrutinizes the importance of multicore processors, virtualization and consolidation techniques for achieving energy efficiency in Cloud computing. It proposes Green Cloud Scheduling Model (GCSM) that exploits the heterogeneity of tasks and resources with the help of a scheduler unit which allocates and schedules deadline-constrained tasks delimited to only energy conscious nodes. GCSM makes energy-aware task allocation decisions dynamically and aims to prevent performance degradation and achieves desired QoS. The evaluation and comparative analysis of the proposed model with two other techniques is done by setting up a Cloud environment. The results indicate that GCSM achieves 71 % of energy savings and high performance in terms of deadline fulfillment.     

A comparative dielectric study of human serum low density lipoprotein before and after partial digestion by trypsin

The relative permittivity of aqueous solutions of human serum low density lipoprotein (LDL) and partially trypsin digested lipoprotein (T-LDL) has been determined for various concentrations at 20°C over the frequency range 0.15–100 MHz. Comparison of the dielectric dispersion curves for the digested lipoprotein with those for the native preparation revealed a larger low-frequency dielectric increment, which may be attributed to an increase in the number of counterions moving over the surface of the molecule. An explanation of this observation is an elevation of 70% in the net negative charge on the surface of the trypsin-treated particle as compared to its native counterpart.     

An overview of cytokines and heat shock response in polytraumatized patients

Early after injury, local tissue damage induces a local and systemic inflammatory response that activates the immune system and leads to the development of systemic inflammatory response syndrome (SIRS). This post-traumatic response often results in uncontrolled release of inflammatory mediators and over-activation of the immune system, which occasionally results in multiple organ dysfunction syndrome (MODS). In parallel, a state of immunosuppression develops. This counter-regulating suppression of different cellular and humoral immune functions has been termed “compensatory anti-inflammatory response syndrome (CARS).” Both SIRS and CARS occur simultaneously even in the initial phase after injury. Pro- and anti-inflammatory cytokines have been suggested to play a major role in development of SIRS, although the degree of involvement of the different cytokines is quite disparate. While TNF-α and IL-1β are quite irrelevant for predicting organ dysfunction, IL-6 is the parameter that best predicts mortality. The hyperinflammatory state seems to be the cause of post-traumatic immunosuppression and heat shock proteins (HSPs), which have been proposed as one of the endogenous stimuli for the deterioration of the immune system acting as danger-associated molecular patterns (DAMPs). Extracellular HSPA1A released from injured tissues increase up to ten times immediately after trauma and even more in patients with MODS. It has powerful immune properties that could contribute to post-traumatic immunosuppression through several mechanisms that have been previously described, so HSPs could represent trauma-associated immunomodulatory mediators. For this reason, HSPA1A has been suggested to be a helpful early prognostic biomarker of trauma after severe injury: serial quantification of serum HSPA1A and anti-Hsp70 concentrations in the first hours after trauma is proposed to be used as a predictive biomarker of MODS and immunosuppression development in polytraumatized patients.     

Effect of population size and selection on Toll-like receptor diversity in populations of Galápagos mockingbirds

The interactions of evolutionary forces are difficult to analyse in free-living populations. However, when properly understood, they provide valuable insights into evolutionary biology and conservation genetics. This is particularly important for the interplay of genetic drift and natural selection in immune genes that confer resistance to disease. The Galápagos Islands are inhabited by four closely related species of mockingbirds (Mimus spp.). We used 12 different-sized populations of Galápagos mockingbirds and one population of their continental relative northern mockingbird (Mimus polyglottos) to study the effects of genetic drift on the molecular evolution of immune genes, the Toll-like receptors (TLRs: TLR1B, TLR4 and TLR15). We found that neutral genetic diversity was positively correlated with island size, indicating an important effect of genetic drift. However, for TLR1B and TLR4, there was little correlation between functional (e.g., protein) diversity and island size, and protein structural properties were largely conserved, indicating only a limited effect of genetic drift on molecular phenotype. By contrast, TLR15 was less conserved and even its putative functional polymorphism correlated with island size. The patterns observed for the three genes suggest that genetic drift does not necessarily dominate selection even in relatively small populations, but that the final outcome depends on the degree of selection constraint that is specific for each TLR locus.