Flash Flood Vulnerability Mapping Based on FFPI Using GIS Spatial Analysis Case Study: Valea Rea Catchment Area, Romania.

The risk associated with extreme hydrological processes (flash floods, floods) is more present than ever, taking into account the global climatic changes, the expansion of inhabited areas and the changes emerging as a result of inadequate land management. Of all the hydrological risks, slope flash floods represent the processes that have the highest impact because of the high speed of their development and their place of origin, which makes them difficult to predict. This study is performed in an area susceptible to the emergence of slope flash floods, the Valea Rea catchment area, spatially located in Northwest Romania, and exposed to western circulation, which favours the development of such processes. The entire research is based on a methodology involving the integration of spatial databases, which indicate the vulnerability of the territory in the form of a weighted average equation to highlight the major impact of the most relevant factor. A number of 15 factors have been used in raster spatial databases, obtained by conversion (land use, soil type, lithology, Hydrologic Soil Group, etc.), derived from the digital elevation model (slope, aspect, TWI, etc.) or by performing spatial analysis submodels (precipitation, slope length, etc). The integration of these databases by means of the spatial analysis equation based on the weighted average led to the vulnerability of the territory to FFPI, classified on five classes from very low to very high. The final result underlines the high and very high vulnerability (43%) of the analysed territory that may have a major impact on the human communities and the territorial infrastructure. The results obtained highlight the torrential nature of the analysed catchment area, identifying several hotspots of great risk, located mainly within the built-up areas of intensely inhabited regions; a fact which involves a major risk and significant potential material damage in the territory. The model was validated by directly comparing the results obtained with locations previously affected, where the flood effects have been identified, highlighting the fact that the model may be taken into account to be applied in practice, and also to be implemented in territories that share the same features.

Transmembrane signal transduction by cofactor transport.

Information processing and cell signalling in biological systems relies on passing chemical signals across lipid bilayer membranes, but examples of synthetic systems that can achieve this process are rare. A synthetic transducer has been developed that triggers catalytic hydrolysis of an ester substrate inside lipid vesicles in response to addition of metal ions to the external vesicle solution. The output signal generated in the internal compartment of the vesicles is produced by binding of a metal ion cofactor to a head group on the transducer to form a catalytically competent complex. The mechanism of signal transduction is based on transport of the metal ion cofactor across the bilayer by the transducer, and the system can be reversibly switched between on and off states by adding cadmium(ii) and ethylene diamine tetracarboxylic acid input signals respectively. The transducer is also equipped with a hydrazide moiety, which allows modulation of activity through covalent conjugation with aldehydes. Conjugation with a sugar derivative abolished activity, because the resulting hydrazone is too polar to cross the bilayer, whereas conjugation with a pyridine derivative increased activity. Coupling transport with catalysis provides a straightforward mechanism for generating complex systems using simple components.

Report of a Novel ALOX12B Mutation in Self-Improving Collodion Ichthyosis with an Overview of the Genetic Background of the Collodion Baby Phenotype.

Collodion baby is a congenital, transient phenotype encountered in approximately 70-90% of autosomal recessive congenital ichthyosis and is an important entity of neonatal erythroderma. The clinical outcome after this severe condition is variable. Genetic mutations of components of the epidermal lipoxygenase pathway have been implicated in the majority of self-improving collodion ichthyosis (SICI). In SICI, the shedding of the collodion membrane reveals clear skin or only mild residual manifestation of ichthyosis. Here we report the case of a girl born with a severe form of collodion baby phenotype, whose skin almost completely cleared within the first month of life. At the age of 3 years, only mild symptoms of a keratinization disorder remained. However, the severity of erythema and scaling showed mild fluctuations over time. To objectively evaluate the skin changes of the patient, we assessed the ichthyosis severity index. Upon sequencing of the ALOX12B gene, we identified a previously unreported heterozygous nonsense mutation, c.1607G>A (p.Trp536Ter) with the recurrent, heterozygous mutation c.1562A>G (p.Tyr521Cys). Thereby, our findings expand the genotypic spectrum of SICI. In addition, we summarize the spectrum of further genetic diseases that can present at birth as collodion baby, in particular the SICI.

Redox switching of an artificial transmembrane signal transduction system.

Transmission of chemical signals across lipid bilayer membranes can be achieved using membrane-anchored molecules, where molecular motion across the bilayer is controlled by switching the polarity of two different head groups. An external redox signal delivered by ascorbic acid was used to trigger membrane translocation in a synthetic transduction system.

Hydroxy Channels-Adaptive Pathways for Selective Water Cluster Permeation.

Artificial water channels (AWCs) are known to selectively transport water, with ion exclusion. Similarly to natural porins, AWCs encapsulate water wires or clusters, offering continuous and iterative H-bonding that plays a vital role in their stabilization. Herein, we report octyl-ureido-polyol AWCs capable of self-assembly into hydrophilic hydroxy channels. Variants of ethanol, propanediol, and trimethanol are used as head groups to modulate the water transport permeabilities, with rejection of ions. The hydroxy channels achieve a single-channel permeability of 2.33 × 108 water molecules per second, which is within the same order of magnitude as the transport rates for aquaporins. Depending on their concentration in the membrane, adaptive channels are observed in the membrane. Over increased concentrations, a significant shift occurs, initiating unexpected higher water permeation. Molecular simulations probe that spongelike or cylindrical aggregates can form to generate transient cluster water pathways through the bilayer. Altogether, the adaptive self-assembly is a key feature influencing channel efficiency. The adaptive channels described here may be considered an important milestone contributing to the systematic discovery of artificial water channels for water desalination.

Liposome Enhanced Detection of Amyloid Protein Aggregates.

Thioflavin-T is used to image amyloid aggregates because of the excellent turn-on fluorescence properties, but binding affinities are low. By mounting multiple dye units on the surface of a vesicle, the binding affinity for α-synuclein fibrils is increased by three orders of magnitude, and the optical response is increased. Cooperative interactions of the dye headgroup and lipid with the protein provide a general strategy for the construction of multivalent amyloid probes based on vesicles.

Triaminopyrimidine derivatives as transmembrane HCl transporters.

Small synthetic molecules capable of inducing transmembrane anion transport have received a lot of attention as potential anti-cancer agents due to their ability to interfere with intracellular pH homeostasis. A series of triaminopyrimidine-based anion transporters have been synthesised, and they are found to diminish proton gradients across lipid bilayers at physiologically relevant pH. The compounds have pKa values (≈7.2) that allow protonation/deprotonation processes coupled with anion binding/unbinding events in physiologically relevant conditions. Synthetic vesicle transport experiments as well as solid state structures indicate synergistic binding of HCl. Cell assays show that the transporters induce apoptosis in various cancerous cell lines.

Imidazole derivatives as artificial water channel building-blocks: structural design influence on water permeability.

A series of mono- and di-ureidoethylimidazole derivatives were tested as self-assembled supramolecular channels for water transport. Several structural behaviours were compared in order to gain insight on the structure-water transport activity relationship. The three main features that are critical to tailor artificial water channel building blocks are: (i) the selectivity of the hydrophilic head, (ii) the H-bonding scaffold favouring the directional self-assembly, and (iii) the lipophilic tail for the compatibility with the hydrophobic environment of the lipid bilayer. The designed compounds bear one or two imidazole heads, one or two urea moieties, and different lipophilic tails. Water transport experiments were performed in order to assess the critical parameters. For that, large unilamellar vesicles (LUV) were fabricated using a mixture of phosphatidylcholine, phosphatidylserine and cholesterol. The bilayer of the LUV constituted a membrane between an intra and an extra vesicular medium. The artificial water channel candidates are put in the presence of this membrane to improve its water permeability. The permeation of elements other than water is ideally maintained to a minimum in order to achieve selective water filtration. In this study the effect of additional urea moieties, as well as its absence, was evidenced as detrimental for the permeation and the influence of the tail was also investigated.

Oriented chiral water wires in artificial transmembrane channels.

Aquaporins (AQPs) feature highly selective water transport through cell membranes, where the dipolar orientation of structured water wires spanning the AQP pore is of considerable importance for the selective translocation of water over ions. We recently discovered that water permeability through artificial water channels formed by stacked imidazole I-quartet superstructures increases when the channel water molecules are highly organized. Correlating water structure with molecular transport is essential for understanding the underlying mechanisms of (fast) water translocation and channel selectivity. Chirality adds another factor enabling unique dipolar oriented water structures. We show that water molecules exhibit a dipolar oriented wire structure within chiral I-quartet water channels both in the solid state and embedded in supported lipid bilayer membranes (SLBs). X-ray single-crystal structures show that crystallographic water wires exhibit dipolar orientation, which is unique for chiral I-quartets. The integration of I-quartets into SLBs was monitored with a quartz crystal microbalance with dissipation, quantizing the amount of channel water molecules. Nonlinear sum-frequency generation vibrational spectroscopy demonstrates the first experimental observation of dipolar oriented water structures within artificial water channels inserted in bilayer membranes. Confirmation of the ordered confined water is obtained via molecular simulations, which provide quantitative measures of hydrogen bond strength, connectivity, and the stability of their dipolar alignment in a membrane environment. Together, uncovering the interplay between the dipolar aligned water structure and water transport through the self-assembled I-quartets is critical to understanding the behavior of natural membrane channels and will accelerate the systematic discovery for developing artificial water channels for water desalting.

Columnar Self-Assemblies of Triarylamines as Scaffolds for Artificial Biomimetic Channels for Ion and for Water Transport.

Triarylamine molecules appended with crown-ethers or carboxylic moieties form self-assembled supramolecular channels within lipid bilayers. Fluorescence assays and voltage clamp studies reveal that the self-assemblies incorporating the crown ethers work as single channels for the selective transport of K+ or Rb+. The X-ray crystallographic structures confirm the mutual columnar self-assembly of triarylamines and crown-ethers. The dimensional fit of K+ cations within the 18-crown-6 leads to a partial dehydration and to the formation of alternating K+ cation-water wires within the channel. This original type of organization may be regarded as a biomimetic alternative of columnar K+-water wires observed for the natural KcsA channel. Supramolecular columnar arrangement was also shown for the triarylamine-carboxylic acid conjugate. In this latter case, stopped-flow light scattering analysis reveals the transport of water across lipid bilayer membranes with a relative water permeability as high as 17 µm s-1.

A class of carbonic anhydrase I - selective activators.

A series of ureido and bis-ureido derivatives were prepared by reacting histamine with alkyl/aryl-isocyanates or di-isocyanates. The obtained derivatives were assayed as activators of the enzyme carbonic anhydrase (CA, EC 4.2.1.1), due to the fact that histamine itself has this biological activity. Although inhibition of CAs has pharmacological applications in the field of antiglaucoma, anticonvulsant, anticancer, and anti-infective agents, activation of these enzymes is not yet properly exploited pharmacologically for cognitive enhancement or Alzheimer's disease treatment, conditions in which a diminished CA activity was reported. The ureido/bis-ureido histamine derivatives investigated here showed activating effects only against the cytosolic human (h) isoform hCA I, having no effect on the widespread, physiologically dominant isoform hCA II. This is the first report in which CA I-selective activators were identified. Such compounds may constitute interesting tools for better understanding the physiological/pharmacological effects connected to activation of this widespread CA isoform, whose physiological function is not fully understood.

Salt-Excluding Artificial Water Channels Exhibiting Enhanced Dipolar Water and Proton Translocation.

Aquaporins (AQPs) are biological water channels known for fast water transport (∼10(8)-10(9) molecules/s/channel) with ion exclusion. Few synthetic channels have been designed to mimic this high water permeability, and none reject ions at a significant level. Selective water translocation has previously been shown to depend on water-wires spanning the AQP pore that reverse their orientation, combined with correlated channel motions. No quantitative correlation between the dipolar orientation of the water-wires and their effects on water and proton translocation has been reported. Here, we use complementary X-ray structural data, bilayer transport experiments, and molecular dynamics (MD) simulations to gain key insights and quantify transport. We report artificial imidazole-quartet water channels with 2.6 Špores, similar to AQP channels, that encapsulate oriented dipolar water-wires in a confined chiral conduit. These channels are able to transport ∼10(6) water molecules/s, which is within 2 orders of magnitude of AQPs' rates, and reject all ions except protons. The proton conductance is high (∼5 H(+)/s/channel) and approximately half that of the M2 proton channel at neutral pH. Chirality is a key feature influencing channel efficiency.

Squalyl Crown Ether Self-Assembled Conjugates: An Example of Highly Selective Artificial K+ Channels.

The natural KcsA K+ channel, one of the best-characterized biological pore structures, conducts K+ cations at high rates while excluding Na+ cations. The KcsA K+ channel is of primordial inspiration for the design of artificial channels. Important progress in improving conduction activity and K+ /Na+ selectivity has been achieved with artificial ion-channel systems. However, simple artificial systems exhibiting K+ /Na+ selectivity and mimicking the biofunctions of the KcsA K+ channel are unknown. Herein, an artificial ion channel formed by H-bonded stacks of squalyl crown ethers, in which K+ conduction is highly preferred to Na+ conduction, is reported. The K+ -channel behavior is interpreted as arising from discreet stacks of dimers resulting in the formation of oligomeric channels, in which transport of cations occurs through macrocycles mixed with dimeric carriers undergoing dynamic exchange within the bilayer membrane. The present highly K+ -selective macrocyclic channel can be regarded as a biomimetic alternative to the KcsA channel.

Controlled supramolecular structure of guanosine monophosphate in the interlayer space of layered double hydroxide.

Guanosine monophosphates (GMPs) were intercalated into the interlayer space of layered double hydroxides (LDHs) and the molecular arrangement of GMP was controlled in LDHs. The intercalation conditions such as GMP/LDH molar ratio and reaction temperature were systematically adjusted. When the GMP/LDH molar ratio was 1:2, which corresponds to the charge balance between positive LDH sheets and GMP anions, GMP molecules were well-intercalated to LDH. At high temperature (100 and 80 °C), a single GMP molecule existed separately in the LDH interlayer. On the other hand, at lower temperature (20, 40 and 60 °C), GMPs tended to form ribbon-type supramolecular assemblies. Differential scanning calorimetry showed that the ribbon-type GMP assembly had an intermolecular interaction energy of ≈101 kJ/mol, which corresponds to a double hydrogen bond between guanosine molecules. Once stabilized, the interlayer GMP orientations, single molecular and ribbon phase, were successfully converted to the other phase by adjusting the external environment by stoichiometry or temperature control.

Supramolecular rulers enabling selective detection of pure short ssDNA via chiral self-assembly.

Multivalent self-assembly of trifunctional aromatic propellers and ssDNA results in the formation of chiral supramolecular assemblies that can be used for the detection of small fragments of ssDNA with different lengths and compositions.

Technical Approach Determines Inflammatory Response after Surgical and Transcatheter Aortic Valve Replacement.

OBJECTIVE: To investigate the periprocedural inflammatory response in patients with isolated aortic valve stenosis undergoing surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) with different technical approaches. MATERIAL AND METHODS: Patients were prospectively allocated to one of the following treatments: SAVR using conventional extracorporeal circulation (CECC, n = 47) or minimized extracorporeal circulation (MECC, n = 15), or TAVI using either transapical (TA, n = 15) or transfemoral (TF, n = 24) access. Exclusion criteria included infection, pre-procedural immunosuppressive or antibiotic drug therapy and emergency indications. We investigated interleukin (IL)-6, IL-8, IL-10, human leukocyte antigen (HLA-DR), white blood cell count, high-sensitivity C-reactive protein (hs-CRP) and soluble L-selectin (sCD62L) levels before the procedure and at 4, 24, and 48 h after aortic valve replacement. Data are presented for group interaction (p-values for inter-group comparison) as determined by the Greenhouse-Geisser correction. RESULTS: SAVR on CECC was associated with the highest levels of IL-8 and hs-CRP (p<0.017, and 0.007, respectively). SAVR on MECC showed the highest descent in levels of HLA-DR and sCD62L (both p<0.001) in the perioperative period. TA-TAVI showed increased intraprocedural concentration and the highest peak of IL-6 (p = 0.017). Significantly smaller changes in the inflammatory markers were observed in TF-TAVI. CONCLUSION: Surgical and interventional approaches to aortic valve replacement result in inflammatory modulation which differs according to the invasiveness of the procedure. As expected, extracorporeal circulation is associated with the most marked pro-inflammatory activation, whereas TF-TAVI emerges as the approach with the most attenuated inflammatory response. Factors such as the pre-treatment patient condition and the extent of myocardial injury also significantly affect inflammatory biomarker patterns. Accordingly, TA-TAVI is to be classified not as an interventional but a true surgical procedure, with inflammatory biomarker profiles comparable to those found after SAVR. Our study could not establish an obvious link between the extent of the periprocedural inflammatory response and clinical outcome parameters.

Self-sorting of dynamic metallosupramolecular libraries (DMLs) via metal-driven selection.

"Metal-driven" selection between finite mononuclear and polymeric metallosupramolecular species can be quantitatively achieved in solution and in a crystalline state via coupled coordination/stacking interactional algorithms within dynamic metallosupramolecular libraries - DMLs.

CD62L (L-selectin) shedding for assessment of perioperative immune sensitivity in patients undergoing cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: To investigate the suitability of blood granulocyte and monocyte sensitivity, as measured by the quantity of different agonists required to induce CD62L shedding, for assessment of perioperative immune changes in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Patients scheduled for aortocoronary bypass grafting or for valve surgery were included in this prospective observational study. Blood samples were drawn before anesthesia induction, directly after surgery and 48 hours after anesthesia induction. We determined the concentration of two different inflammatory stimuli--lipoteichoic acid (LTA) and tumor necrosis factor alpha (TNF)--required to induce shedding of 50% of surface CD62L from blood granulocytes and monocytes. In parallel monocyte surface human leukocyte antigen (HLA)-DR, and plasma interleukin (IL)-8, soluble (s)CD62L, soluble (s)Toll-like receptor (TLR)-2 and ADAM17 quantification were used to illustrate perioperative immunomodulation. RESULTS: 25 patients were enrolled. Blood granulocytes and monocytes showed decreased sensitivity to the TLR 2/6 agonist Staphylococcus aureus LTA immediately after surgery (p = 0.001 and p = 0.004 respectively). In contrast, granulocytes (p = 0.01), but not monocytes (p = 0.057) displayed a decreased postoperative sensitivity to TNF. We confirmed the presence of a systemic inflammatory response and a decreased immune sensitivity in the post-surgical period by measuring significant increases in the perioperative plasma concentration of IL-8 (p ≤ 0.001) and sTLR (p = 0.004), and decreases in monocyte HLA-DR (p<0.001), plasma sCD62L (p ≤ 0.001). In contrast, ADAM17 plasma levels did not show significant differences over the observation period (p = 0.401). CONCLUSIONS: Monitoring granulocyte and monocyte sensitivity using the "CD62L shedding assay" in the perioperative period in cardiac surgical patients treated with the use of cardiopulmonary bypass reveals common changes in sensitivity to TLR2/6 ligands and to TNF stimulus. Further long-term follow-up studies will address the predictive value of these observations for clinical purposes.

Characteristics of nosocomial bloodstream infections at a Hungarian cardiac surgery centre.

Nosocomial bloodstream infection (BSI) is a common finding in cardiac surgery intensive care units and is associated with excess mortality and hospital costs. Additional data are needed about incidence, characteristics, predictors, associated microorganisms of nosocomial BSI in cardiac surgical patients in order to refine measures to prevent nosocomial infections and to improve recovery outcomes in this patient population. The 3912 cardio-thoracic surgery patients from all age groups were admitted to the study at the Gottsegen György Hungarian Institute of Cardiology between January 1999 and December 2000. In each patient with BSI demographic, epidemiological and clinical variables were recorded along with potential risk factors. Incidence of associated pathogens and their possible sources were evaluated and outcome and mortality risk factors were assessed. There were a total of 134 episodes of BSI. The incidence was 34.25 per 1000 admissions. The leading microorganisms were staphylococci (37.7%). Bacteremic episodes developed secondary to an identifiable source in 27.6% of the cases, or were catheter-related (16.4%). In 56% of the cases the source was not identified. The crude mortality rate was 33.3%. Higher mortality rate was associated with intracardial grafts (p < 0.05), low left ventricular ejection fraction (p < 0.04), diabetes mellitus (p < 0.05), an age above 16 years (p < 0.02), severe sepsis (p < 0.001) and high APACHE II score (p < 0.001). As the identified main sources of BSI were intravascular lines, mortality from BSI could probably be reduced by paying more attention to the prevention, early recognition and prompt management of intravascular device associated infections.