Revisiting a perovskite-like copper-formate framework NH4[Cu(HCOO)3]: order-disorder transition influenced by Jahn-Teller distortion and above room-temperature switching of the nonlinear optical response between two SHG-active states

Metal-formate frameworks comprising ammonium cations as guests are proven to be a fertile ground to study various phenomena associated with the temperature-induced changes in structural, dielectric, optical, and magnetic properties. In this contribution, we revisit NH4[Cu(HCOO)3], a member of metal formates that distinguishes itself in terms of its phase transition behavior and associated properties. New data on structural dynamics of all phases of NH4[Cu(HCOO)3] have been obtained with the use of variable-temperature Raman measurements. Smooth changes of band positions observed near 220 K attest to the postulated continuous nature of low-temperature phase transition, whereas apparent discontinuities at 355 K confirm the first-order type of transition between orthorhombic (II) and hexagonal (I) phases. Low-temperature Raman data were confronted with diffraction results, pointing to a significant effect of Jahn-Teller distortion on the vibrational properties the CuO6 subnetwork. In the high-temperature range, a significant broadening of bands is observed, confirming that phase I is highly disordered, with the strongest changes of full width at half maximum (FWHM) parameters being observed for bands corresponding to NH4+ cations. Dielectric investigations revealed the symmetric shape of the observed process indicating the Debye-like relaxation. Thus, the dielectric relaxation was characterized in terms of the dipolar relaxation model using the Cole–Cole relaxation function, leading to an Ea value of approximately 0.76 eV. Finally, temperature-resolved second harmonic generation (SHG) measurements unequivocally corroborate the noncentrosymmetric setting of phases II and I, as well as allowed us to realize temperature-induced switching of second-order nonlinear optical (NLO) responses. We demonstrate that NH4[Cu(HCOO)3] serves as a host to uncommon kind of quadratic NLO switching, which takes advantage of two SHG-active states: SHG-high state below Tc, and SHG-low state above Tc. The demonstrated SHG-high – SHG-low temperature-driven bistability stands out from the vast majority of molecular and coordination polymer NLO switches that employ binary SHG-on and SHG-off switching schemes

The effect of insulin and sulodexide (Vessel Due F) on diabetic foot syndrome. Pilot study in elderly patients

Celem pracy była ocena skuteczności stosowania insuliny wraz z sulodeksydem (mieszanina 80% pochodnych heparyny i 20% siarczanu dermatanu) w leczeniu owrzodzeń stóp oraz określenie ich wpływu na mikrokrążenie skórne i neuropatię cukrzycową. Chorzy z zaawansowaną neuropatią cukrzycową i owrzodzeniem stopy losowo przydzielono do grupy leczonej insuliną (I) z sulodeksydem (S) (n = 12) lub do grupy kontrolnej leczonej insuliną z placebo (P) (n = 6) przez 10 tygodni. Za pomocą metody dopplerowskiego lasera oceniano skórny przepływ krwi w stopach (LDF, laser doppler flow) w spoczynku oraz po 30- i 60-sekundowym niedokrwieniu. Ocenie poddano również przewodnictwo nerwowe na podstawie czuciowych i ruchowych potencjałów wywołanych. U chorych na cukrzycę skórny przepływ po niedokrwieniu był 2,5 raza krótszy w kończynie z owrzodzeniem niż w stopie zdrowej. Obserwowano znamienny wzrost przepływów skórnych po 30- i 60-sekundowym niedokrwieniu po zakończeniu terapii (grupa IS, owrzodzenie stopy, LDF - 60 s; od 99,1 &plusmn; 14,3 do 218,6 &plusmn; 28,6 PU, p < 0,001, grupa od 110,5 &plusmn; 13,0 do 164,8 &plusmn; 15,4 PU, p < 0,05). Czas przekrwienia reaktywnego uległ wydłużeniu w grupie IS (IS: od 30,3 &plusmn; 2,9 do 43,9 &plusmn; 2,2 s, p < 0,001; IP: od 28,7 &plusmn; 3,0 do 33,3 &plusmn; 3,3 s, NS). W grupie IS 92% owrzodzeń stóp uległo zagojeniu w ciągu 46,4 dnia, natomiast w grupie IP 83% w ciągu 63,0 dnia. Badania przewodnictwa nerwowego nie wykazały różnic nasilenia neuropatii w obrębie grup i pomiędzy grupami. W stopach z owrzodzeniami sulodeksyd i insulina poprawiają przepływ skórny w odpowiedzi na niedokrwienie, nie wpływając na przewodnictwo nerwowe. Kliniczne efekty działania sulodeksydu, sumując się z działaniami insuliny, mogą istotnie skracać czas niezbędny do całkowitego wyleczenia owrzodzenia. Ostateczne potwierdzenie przedstawionych wstępnych wyników wymaga dalszych badań klinicznych.To assess the efficacy of insulin plus sulodexide (a mixture of 80% heparin-like substances and 20% dermatan sulphate) on diabetic ulcers, and its influence on foot skin microcirculation and diabetic neuropathy. Two groups of diabetic patients, suffering from severe neuropathy and ulceration, were randomly assigned to insulin (I) plus sulodexide (S) (n = 12) or insulin plus placebo (P) (n = 6) therapy, for 10 weeks. Laser Doppler assessment of foot skin flow (LDF), at rest and 30 or 60 s after arterial occlusion, and nerve conduction tests (sensorial evoked and motoric conduction potentials) have been evaluated in both groups. Postischaemic flow was 2.5 times shorter in ulcerated vs. non-ulcerated feet in diabetic patients. A significant increase in flows after 30 and 60 s ischaemia was detected in both groups at the end of therapy (IS group, ulcerated foot, LDF = 60 s: from 99.1 &#177; 14.3 to 218.6 &#177; 28.6 PU, P < 0.001. IP group = from 110.5 &#177; 13.0 to 164.8 &#177; 15.4 PU, P < 0.05). The length of reactive hyperaemia was higher in IS vs. IP group (IS: from 30.3 &#177; 2.9 to 43.9 &#177; 2.2 s, P < 0.001; IP: from 28.7 &#177; 3.0 to 33.3 &#177; 3.3 s, ns). Ninety-two percent of ulcers heals in a mean time of 46.4 days (IS group) vs. 83% and 63.0 days, respectively, in IP group. Nerve conduction studies have not demonstrated within- and between-group differences. Sulodexide and insulin improve the postischaemic skin flow in ulcerated feet, without affecting nerve conduction tests. The effect of sulodexide results additive to insulin; it is clinically relevant, in the view of the possibility of reducing the time needed to completely heal ulcers. The ultimate validation of these preliminary results requires extensive trials

[Methylhydrazinium]2PbBr4, a ferroelectric hybrid organic-inorganic perovskite with multiple nonlinear optical outputs

An expansive library of structurally complex two-dimensional (2D) and three-dimensional (3D) lead halide perov-skites has emerged over the past decade, finding applications in various aspects of photon management: photovoltaics, photo-detection, light emission, and nonlinear optics. Needless to say, the highest degree of structural plasticity enjoys the former group, offering a rich playground for modifications of relevant optoelec-tronic parameters such as exciton energy. Structural tailorability is reflected in the ease of modification of the chemistry of the organic layers residing between inorganic slabs. In this vein, we show that the introduction of methylhydrazinium cation (MHy+, CH3NH2NH2+) into 2D perovskite gives a material with a record low separation of the inorganic layers (8.91 Å at 300 K). Optical studies showed that MHy2PbBr4 features the most red-shifted excitonic absorption among all known A2PbBr4 compounds as well as a small exciton binding energy of 99.9 meV. MHy2PbBr4 crystallizes in polar Pmn21 symmetry at room emperature (phase III) and at 351 K undergoes a phase transition to modulated Pmnm phase (II) followed by another phase transition at 371 K to Pmnm phase (I). The ferroelectric property of room-temperature phase III is inferred from switching of the pyrocurrent, dielectric measurements, and optical birefringence results. MHy2PbBr4 exhibits multiple nonlinear optical phenomena such as second-harmonic generation, third-harmonic generation, two-photon excited luminescence, and multiphoton excited luminescence. Analysis of MHy2PbBr4 single-crystal luminescence spectra obtained through linear and nonlinear optical excitation pathways indicates that free exciton emission is readily probed by the ultraviolet excitation, whereas crumpled exciton emission is detected under two- and multiphoton excitation conditions. Overall, our results demonstrate that incorporation of MHy+ into the organic layer is an emergent strategy for obtaining a 2D perovskite with polar character and multifunctional properties

Genetic Pathway in Acquisition and Loss of Vancomycin Resistance in a Methicillin Resistant Staphylococcus aureus (MRSA) Strain of Clonal Type USA300

An isolate of the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 with reduced susceptibility to vancomycin (SG-R) (i.e, vancomycin-intermediate S. aureus, VISA) and its susceptible “parental” strain (SG-S) were recovered from a patient at the end and at the beginning of an unsuccessful vancomycin therapy. The VISA phenotype was unstable in vitro generating a susceptible revertant strain (SG-rev). The availability of these 3 isogenic strains allowed us to explore genetic correlates of antibiotic resistance as it emerged in vivo. Compared to the susceptible isolate, both the VISA and revertant strains carried the same point mutations in yycH, vraG, yvqF and lspA genes and a substantial deletion within an intergenic region. The revertant strain carried a single additional frameshift mutation in vraS which is part of two component regulatory system VraSR. VISA isolate SG-R showed complex alterations in phenotype: decreased susceptibility to other antibiotics, slow autolysis, abnormal cell division and increased thickness of cell wall. There was also altered expression of 239 genes including down-regulation of major virulence determinants. All phenotypic properties and gene expression profile returned to parental levels in the revertant strain. Introduction of wild type yvqF on a multicopy plasmid into the VISA strain caused loss of resistance along with loss of all the associated phenotypic changes. Introduction of the wild type vraSR into the revertant strain caused recovery of VISA type resistance. The yvqF/vraSR operon seems to function as an on/off switch: mutation in yvqF in strain SG-R turns on the vraSR system, which leads to increase in vancomycin resistance and down-regulation of virulence determinants. Mutation in vraS in the revertant strain turns off this regulatory system accompanied by loss of resistance and normal expression of virulence genes. Down-regulation of virulence genes may provide VISA strains with a “stealth” strategy to evade detection by the host immune system

Evolution of Multidrug Resistance during Staphylococcus aureus Infection Involves Mutation of the Essential Two Component Regulator WalKR

Antimicrobial resistance in Staphylococcus aureus is a major public health threat, compounded by emergence of strains with resistance to vancomycin and daptomycin, both last line antimicrobials. Here we have performed high throughput DNA sequencing and comparative genomics for five clinical pairs of vancomycin-susceptible (VSSA) and vancomycin-intermediate ST239 S. aureus (VISA); each pair isolated before and after vancomycin treatment failure. These comparisons revealed a frequent pattern of mutation among the VISA strains within the essential walKR two-component regulatory locus involved in control of cell wall metabolism. We then conducted bi-directional allelic exchange experiments in our clinical VSSA and VISA strains and showed that single nucleotide substitutions within either walK or walR lead to co-resistance to vancomycin and daptomycin, and caused the typical cell wall thickening observed in resistant clinical isolates. Ion Torrent genome sequencing confirmed no additional regulatory mutations had been introduced into either the walR or walK VISA mutants during the allelic exchange process. However, two potential compensatory mutations were detected within putative transport genes for the walK mutant. The minimal genetic changes in either walK or walR also attenuated virulence, reduced biofilm formation, and led to consistent transcriptional changes that suggest an important role for this regulator in control of central metabolism. This study highlights the dramatic impacts of single mutations that arise during persistent S. aureus infections and demonstrates the role played by walKR to increase drug resistance, control metabolism and alter the virulence potential of this pathogen

Analysing the Coupled Effects of Compressive and Diffusion Induced Stresses on the Nucleation and Propagation of Circular Coating Blisters in the Presence of Micro-cracks

This paper presents the delamination of coating with micro-cracks under compressive residual stress coupled with diffusion induced stress. Micro-cracks in coating provide a passage for corrosive species towards the coating-substrate interface which in turn produces diffusion induced stress in the coating. Micro-cracks contract gradually with increasing compressive residual stress in coating due to thermal expansion mismatch which blocks the species diffusion towards the interface. This behaviour reduces the diffusion induced stress in the coating while the compressive residual stress increases. With further increase in compressive residual stress, micro-cracks reach to the point, where they cannot be constricted any further and a high compressive residual stress causes the coating to buckle away from the substrate resulting in delamination and therefore initiating blistering. Blistering causes the contracted micro-cracks to wide open again which increases diffusion induced stress along with high compressive residual stress. The high resultant stress in coating causes the blister to propagate in an axis-symmetric circular pattern. A two-part theoretical approach has been utilised coupling the thermodynamic concepts with the mechanics concepts. The thermodynamic concepts involve the corrosive species transportation through micro-cracks under increasing compression, eventually causing blistering, while the fracture mechanics concepts are used to treat the blister growth as circular defect propagation. The influences of moduli ratio, thickness ratio, thermal mismatch ratio, poisson’s ratio and interface roughness on blister growth are discussed. Experiment is reported for blistering to allow visualisation of interface and to permit coupled (diffusion and residual) stresses in the coating over a full range of interest. The predictions from model show excellent, quantitative agreement with the experimental results

Modified cantilever arrays improve sensitivity and reproducibility of nanomechanical sensing in living cells

Mechanical signaling involved in molecular interactions lies at the heart of materials science and biological systems, but the mechanisms involved are poorly understood. Here we use nanomechanical sensors and intact human cells to provide unique insights into the signaling pathways of connectivity networks, which deliver the ability to probe cells to produce biologically relevant, quantifiable and reproducible signals. We quantify the mechanical signals from malignant cancer cells, with 10 cells per ml in 1000-fold excess of non-neoplastic human epithelial cells. Moreover, we demonstrate that a direct link between cells and molecules creates a continuous connectivity which acts like a percolating network to propagate mechanical forces over both short and long length-scales. The findings provide mechanistic insights into how cancer cells interact with one another and with their microenvironments, enabling them to invade the surrounding tissues. Further, with this system it is possible to understand how cancer clusters are able to co-ordinate their migration through narrow blood capillaries

Modulating Activity of Vancomycin and Daptomycin on the Expression of Autolysis Cell-Wall Turnover and Membrane Charge Genes in hVISA and VISA Strains

Glycopeptides are still the gold standard to treat MRSA (Methicillin Resistant Staphylococcus aureus) infections, but their widespread use has led to vancomycin-reduced susceptibility [heterogeneous Vancomycin-Intermediate-Staphylococcus aureus (hVISA) and Vancomycin-Intermediate-Staphylococcus aureus (VISA)], in which different genetic loci (regulatory, autolytic, cell-wall turnover and cell-envelope positive charge genes) are involved. In addition, reduced susceptibility to vancomycin can influence the development of resistance to daptomycin. Although the phenotypic and molecular changes of hVISA/VISA have been the focus of different papers, the molecular mechanisms responsible for these different phenotypes and for the vancomycin and daptomycin cross-resistance are not clearly understood. The aim of our study was to investigate, by real time RT-PCR, the relative quantitative expression of genes involved in autolysis (atl-lytM), cell-wall turnover (sceD), membrane charges (mprF-dltA) and regulatory mechanisms (agr-locus-graRS-walKR), in hVISA and VISA cultured with or without vancomycin and daptomycin, in order to better understand the molecular basis of vancomycin-reduced susceptibility and the modulating activity of vancomycin and daptomycin on the expression of genes implicated in their reduced susceptibility mechanisms. Our results show that hVISA and VISA present common features that distinguish them from Vancomycin-Susceptible Staphylococcus aureus (VSSA), responsible for the intermediate glycopeptide resistance i.e. an increased cell-wall turnover, an increased positive cell-wall charge responsible for a repulsion mechanism towards vancomycin and daptomycin, and reduced agr-functionality. Indeed, VISA emerges from hVISA when VISA acquires a reduced autolysis caused by a down-regulation of autolysin genes, atl/lytM, and a reduction of the net negative cell-envelope charge via dltA over-expression. Vancomycin and daptomycin, acting in a similar manner in hVISA and VISA, can influence their cross-resistance mechanisms promoting VISA behavior in hVISA and enhancing the cell-wall pathways responsible for the intermediate vancomycin resistance in VISA. Daptomycin can also induce a charge repulsion mechanism both in hVISA and VISA increasing the activity of the mprF

Effect of Low Temperature on Growth and Ultra-Structure of Staphylococcus spp

The effect of temperature fluctuation is an important factor in bacterial growth especially for pathogens such as the staphylococci that have to remain viable during potentially harsh and prolonged transfer conditions between hosts. The aim of this study was to investigate the response of S. aureus, S. epidermidis, and S. lugdunensis when exposed to low temperature (4°C) for prolonged periods, and how this factor affected their subsequent growth, colony morphology, cellular ultra-structure, and amino acid composition in the non-cytoplasmic hydrolysate fraction. Clinical isolates were grown under optimal conditions and then subjected to 4°C conditions for a period of 8 wks. Cold-stressed and reference control samples were assessed under transmission electron microscopy (TEM) to identify potential ultra-structural changes. To determine changes in amino acid composition, cells were fractured to remove the lipid and cytoplasmic components and the remaining structural components were hydrolysed. Amino acid profiles for the hydrolysis fraction were then analysed for changes by using principal component analysis (PCA). Exposure of the three staphylococci to prolonged low temperature stress resulted in the formation of increasing proportions of small colony variant (SCV) phenotypes. TEM revealed that SCV cells had significantly thicker and more diffuse cell-walls than their corresponding WT samples for both S. aureus and S. epidermidis, but the changes were not significant for S. lugdunensis. Substantial species-specific alterations in the amino acid composition of the structural hydrolysate fraction were also observed in the cold-treated cells. The data indicated that the staphylococci responded over prolonged periods of cold-stress treatment by transforming into SCV populations. The observed ultra-structural and amino acid changes were proposed to represent response mechanisms for staphylococcal survival amidst hostile conditions, thus maintaining the viability of the species until favourable conditions arise again