We have synthesized a series of N-phenylpyrrole and N-phenylindole carbenes and used them as ruthenium-ligating moieties in the synthesis of Hoveyda-Grubbs catalyst derivatives. We show that most of ...these complexes are difficult to synthesize and unstable apart from the N-phenylpyrrole-2,6-diisopropylphenyl ruthenium complex and its perbrominated derivative. These two systems are almost completely inactive in ring-closing metathesis at room temperature and become active only at 80 °C. DFT, SAPT0 and DLPNO-CCSD(T) calculations suggest that the rarely occurring phenyl-ruthenium interactions are responsible for the very slow initiation of these precatalysts at low temperatures.
Objective Recently the fast progress in the development of systems attending the three-dimensional gait evaluation is being observed. One of the indexes used to the analysis is Gillette Gait Index ...(GGI), complying 16 clinically meaningful kinematic and three-dimensional parameters. Methods The study was conducted with application of the three-dimensional system of gait analysis BTS Smart and carried by the team of pediatric neurologists, physiotherapists and engineers. Spatial-time parameters of gait and courses of angles of joint of lower limbs were determined on the basis of conducted research. Those parameters were used in estimation of Gillette Gait Index. The analyzed group consisted of ten CP patients treated with botulin toxin (three children with hemiparesis, seven with diparesis), intensively rehabilitated after the botulin treatment. The data were compared to four patients put on rehabilitation without the botulin treatment. The patients treated with botulin were evaluated three times: before the botulin administration, then three and six months after it. In the other patients' group the evaluation was conducted three months after rehabilitation start. The results of gait evaluation were compared to the gait pattern of the healthy children; the normal values were worked out by the authors. Results After the botulin treatment and rehabilitation the increase of the gait speed and frequency of steps were observed; the GGI decreased both after three and six months of observation. The locomotive function of the patients' improved in 70% of them. Conclusion The authors regard the results presented above as the pilot-study; the evaluation of the larger groups of children with cerebral palsy is conducted. In the authors' opinion the objective method of CP children gait evaluation may be the helpful tool for clinicians to optimize the way of CP children treatment. Study realized as a part of the DEC-2011/01/B/NZ7/02695 project, financed by National Science Centre.
The synthesis of potassium 6-hydroxy-7-chloro-1,1-dimethyl-3,3-difluorobenzo-1,2,3-siloxaborolate 5b from readily available 4-bromo-2-chlorophenol was developed. This compound proved useful in ...various derivatizations resulting in a wide range of
-functionalized benzosiloxaboroles. Reactions of 5b with selected substituted benzoyl chlorides gave rise to a series of respective derivatives with 6-benzoate side groups attached to the benzosiloxaborole core. Furthermore, treatment of 5b with substituted benzenesufonyl chlorides afforded several benzosiloxaboroles bearing functionalized benzenesulfonate moieties at the 6 position. The synthesis of related chloropyridine-2-yloxy substituted benzosiloxaboroles was accomplished by a standard approach involving silylation/boronation of appropriate heterodiaryl ethers. Investigation of biological activity of obtained compounds revealed that some benzoate and most benzenesulfonate derivatives exhibit high activity against Gram-positive cocci such as methicillin-sensitive
ATCC 6538P as well as methicillin-resistant
ATCC 43300 with the MIC values in the range of 0.39-3.12 mg L
. Some benzenesulfonate derivatives showed also potent activity against
ATCC 29212 and
ATCC 6057 with MIC = 6.25 mg L
. Importantly, for the most promising cocci-active benzenesulfonate derivatives the obtained MIC values were far below the cytotoxicity limit determined with respect to human normal lung fibroblasts (MRC-5). For those derivatives, the obtained IC
values were higher than 12.3 mg L
. The results of antimicrobial activity and cytotoxicity indicate that the tested compounds can be considered as potential antibacterial agents.
This Letter presents measurements of the elliptic flow of charged particles as a function of pseudorapidity and centrality from Cu-Cu collisions at 62.4 and 200 GeV using the PHOBOS detector at the ...Relativistic Heavy Ion Collider. The elliptic flow in Cu-Cu collisions is found to be significant even for the most central events. For comparison with the Au-Au results, it is found that the detailed way in which the collision geometry (eccentricity) is estimated is of critical importance when scaling out system-size effects. A new form of eccentricity, called the participant eccentricity, is introduced which yields a scaled elliptic flow in the Cu-Cu system that has the same relative magnitude and qualitative features as that in the Au-Au system.
In relativistic heavy-ion collisions, anisotropic collective flow is driven, event by event, by the initial eccentricity of the matter created in the nuclear overlap zone. Interpretation of the ...anisotropic flow data thus requires a detailed understanding of the effective initial source eccentricity of the event sample. In this paper, we investigate various ways of defining this effective eccentricity using the Monte Carlo Glauber (MCG) approach. In particular, we examine the participant eccentricity, which quantifies the eccentricity of the initial source shape by the major axes of the ellipse formed by the interaction points of the participating nucleons. We show that reasonable variation of the density parameters in the Glauber calculation, as well as variations in how matter production is modeled, do not significantly modify the already established behavior of the participant eccentricity as a function of collision centrality. Focusing on event-by-event fluctuations and correlations of the distributions of participating nucleons, we demonstrate that, depending on the achieved event-plane resolution, fluctuations in the elliptic flow magnitude v{sub 2} lead to most measurements being sensitive to the root-mean-square rather than the mean of the v{sub 2} distribution. Neglecting correlations among participants, we derive analytical expressions for the participant eccentricity cumulants as a function of the number of participating nucleons, N{sub part}, keeping nonnegligible contributions up to O(1/N{sub part}{sup 3}). We find that the derived expressions yield the same results as obtained from mixed-event MCG calculations which remove the correlations stemming from the nuclear collision process. Most importantly, we conclude from the comparison with MCG calculations that the fourth-order participant eccentricity cumulant does not approach the spatial anisotropy obtained assuming a smooth nuclear matter distribution. In particular, for the Cu+Cu system, these quantities deviate from each other by almost a factor of 2 over a wide range in centrality. This deviation reflects the essential role of participant spatial correlations in the interaction of two nuclei.
Nonhealing wounds can be a major clinical problem. Impaired wound healing is often related to massive tissue injury, concomitant wound healing deficiencies (chronic wounds), burn injury, or ...congenital conditions. We propose a novel biological dressing as an alternative surgical approach. The dressing is a form of an allogenic human skin graft equivalent with further use of allogeneic stem cells classified as an advanced therapy medicinal product. This new allogenic acellular human skin graft has been specifically developed to address the clinical indications for dressing wound lesions and promoting tissue repair in specific rare genetic diseases.
This case report illustrates the use of an acellular human skin allograft seeded with multipotent stem cells in the treatment of tissue injuries (burns), congenital conditions, and chronic wounds. Donor-tissue processing yields an acellular dermal matrix with integral collagen bundling and organization, as well as an intact basement membrane complex.
Preclinical observations show prolonged viability of acellular human skin grafts with multipotent stem cells. This was confirmed with histological and electron-microscopic evaluation of biopsies, which demonstrated host-cell infiltration and neovascularization of the biological dressing. Moreover, the dressings were characterized by low immunogenicity, as confirmed by histology exam and T-cell proliferation assays in vitro.
Our data confirmed the safety and efficacy of the evaluated acellular human skin grafts, which may be used in patients with rare diseases, such as epidermolysis bullosa, burn injuries, and chronic wounds.
Epidermolysis bullosa (EB) is a phenotypically diverse group of hereditary blistering disorders involving mutations in 20 different genes. Those debilitating disorders are currently incurable; ...however, there are a number of promising preclinical trials, where some treatments already approach the stage of early clinical trial. In this paper we introduce a novel surgical approach to the treatment of EB-induced ulcerations.
The purpose of our study was to evaluate the safety and efficacy of a new biological dressing in the form of an allogenic human skin equivalent graft before using multipotent stem cells, classified as an advanced therapy medicinal product.
Implanted human acellular dermal matrices were prepared from the superficial layers of donated human skin. Scaffold sterilization was conducted via irradiation with the use of a linear electron accelerator. Following water-knife debridement, wounds were surgically covered with accordingly prepared grafts and dressed in burn-injury fashion. Subsequently, the wounds were monitored for infection and viability.
Our data indicate that grafting as a potential new medicinal product was safe and effective in patients with rare diseases, such as EB, and may be used for stem cells to create new Advanced Therapy Medicinal Products. During a 200-day follow-up, we proved the safety of using human scaffolds (allogeneic graft) by observing no apparent infection or necrosis. Instead, we noted fewer required dressing changes, promoted wound healing, pain reduction, and an overall improvement in the quality of life in patients with EB.
The protocol for grafting allogenic acellular epidermal sheets is the most promising treatment for severely affected skin areas in EB patients to date.
Hailey-Hailey disease (HHD) is a rare, late-onset autosomal dominant genodermatosis characterized by blisters, vesicular lesions, crusted erosions, and erythematous scaly plaques predominantly in ...intertriginous regions. HHD is caused by
ATP2C1
mutations. About 180 distinct mutations have been identified so far; however, data of only few cases from Central Europe are available. The aim was to analyze the
ATP2C1
gene in a cohort of Polish HHD patients. A group of 18 patients was enrolled in the study based on specific clinical symptoms. Mutations were detected using Sanger or next generation sequencing. In silico analysis was performed by prediction algorisms and dynamic structural modeling. In two cases, mRNA analysis was performed to confirm aberrant splicing. We detected 13 different mutations, including 8 novel, 2 recurrent (p.Gly850Ter and c.325-3 T > G), and 6 sporadic (c.423-1G > T, c.899 + 1G > A, p.Leu539Pro, p.Thr808TyrfsTer16, p.Gln855Arg and a complex allele: c.1610C > G;1741 + 3A > G). In silico analysis shows that all novel missense variants are pathogenic or likely pathogenic. We confirmed pathogenic status for two novel variants c.325-3 T > G and c.1610C > G;1741 + 3A > G by mRNA analysis. Our results broaden the knowledge about genetic heterogeneity in Central European patients with
ATP2C1
mutations and also give further evidence that careful and multifactorial evaluation of variant pathogenicity status is essential.
PDF
