Relaxation processes of point defects in vitreous silica from femtosecond to nanoseconds

We studied ultrafast relaxation of localized excited states at Ge-related oxygen deficient centers in silica using femtosecond transient-absorption spectroscopy. The relaxation dynamics exhibits a biexponential decay, which we ascribe to the departure from the Frank-Condon region of the first excited singlet state in 240 fs, followed by cooling in ∼10 ps. At later times, a nonexponential relaxation spanning up to 40 ns occurs, which is fitted with an inhomogeneous distribution of nonradiative relaxation rates, following a chi-square distribution with one degree of freedom. This reveals several analogies with phenomena such as neutron reactions, quantum dot blinking, or intramolecular vibrational redistribution. © 2008 American Institute of Physics.Peer Reviewe

Оценка состояния протяженных выработок с длительным сроком службы шахт Центрального Донбасса на примере Шахтоуправления «Покровское»

Chemokines critically control the infiltration of immune cells upon liver injury, thereby promoting hepatic inflammation and fibrosis. The chemokine receptor CCR8 can affect trafficking of monocytes/macrophages, monocyte-derived dendritic cells (DCs) and T-helper cell (Th) subsets, but its role in liver diseases is currently unknown. To investigate the functional role of CCR8 in liver diseases, ccr8(−/−) and wild-type (WT) mice were subjected to chronic experimental injury models of carbon tetrachloride (CCl(4)) administration and surgical bile duct ligation (BDL). CCR8 was strongly up-regulated in the injured liver. Ccr8(−/−) mice displayed attenuated liver damage (e.g., ALT, histology, and TUNEL) compared to WT mice and were also protected from liver fibrosis in two independent injury models. Flow cytometry revealed reduced infiltrates of liver macrophages, neutrophils and natural killer cells, whereas hepatic CD4(+) T cells increased. The main CCR8-expressing cells in the liver were hepatic macrophages, and CCR8 was functionally necessary for CCL1-directed migration of inflammatory but not for nonclassical monocytes into the liver. Moreover, the phenotype of liver macrophages from injured ccr8(−/−) animals was altered with increased expression of DC markers and enhanced expression of T-cell-attracting chemokine macrophage inflammatory protein 1-alpha (MIP-1α/CCL3). Correspondingly, hepatic CD4(+) T cells showed increased Th1 polarization and reduced Th2 cells in CCR8-deficient animals. Liver fibrosis progression, but also subsequent T-cell alterations, could be restored by adoptively transferring CCR8-expressing monocytes/macrophages into ccr8(−/−) mice during experimental injury. CONCLUSIONS: CCR8 critically mediates hepatic macrophage recruitment upon injury, which subsequently shapes the inflammatory response in the injured liver, affecting macrophage/DC and Th differentiation. CCR8 deficiency protects the liver against injury, ameliorating initial inflammatory responses and hepatic fibrogenesis. Inhibition of CCR8 or its ligand, CCL1, might represent a successful therapeutic target to limit liver inflammation and fibrosis progression

Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults

<p>Abstract</p> <p>Background</p> <p>Recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. In order to possibly translate these findings into human physiology and pathophysiology, human monocyte subsets need to be carefully revisited in health and disease. In analogy to murine studies, we hypothesized that human monocyte subsets dynamically change during ageing, potentially influencing their functionality and contributing to immunosenescence.</p> <p>Results</p> <p>Circulating monocyte subsets, surface marker and chemokine receptor expression were analyzed in 181 healthy volunteers (median age 42, range 18-88). Unlike the unaffected total leukocyte or total monocyte counts, non-classical CD14⁺CD16⁺monocytes significantly increased with age, but displayed reduced HLA-DR and CX₃CR1 surface expression in the elderly. Classical CD14⁺⁺CD16^-monocyte counts did not vary dependent on age. Serum MCP-1 (CCL2), but not MIP1α (CCL3), MIP1β (CCL4) or fractalkine (CX₃CL1) concentrations increased with age. Monocyte-derived macrophages from old or young individuals did not differ with respect to cytokine release <it>in vitro </it>at steady state or upon LPS stimulation.</p> <p>Conclusions</p> <p>Our study demonstrates dynamic changes of circulating monocytes during ageing in humans. The expansion of the non-classical CD14⁺CD16⁺subtype, alterations of surface protein and chemokine receptor expression as well as circulating monocyte-related chemokines possibly contribute to the preserved functionality of the monocyte pool throughout adulthood.</p

Exposure of Candida parapsilosis to the silver(I) compound SBC3 induces alterations in the proteome and reduced virulence

The antimicrobial properties of silver have been exploited for many centuries and continue to gain interest in the fight against antimicrobial drug resistance. The broad-spectrum activity and low toxicity of silver have led to its incorporation into a wide range of novel antimicrobial agents, including N-heterocyclic carbene (NHC) complexes. The antimicrobial activity and in vivo efficacy of the NHC silver(I) acetate complex SBC3, derived from 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*), have previously been demonstrated, although the mode(s) of action of SBC3 remains to be fully elucidated. Label-free quantitative proteomics was applied to analyse changes in protein abundance in the pathogenic yeast Candida parapsilosis in response to SBC3 treatment. An increased abundance of proteins associated with detoxification and drug efflux were indicative of a cell stress response, whilst significant decreases in proteins required for protein and amino acid biosynthesis offer potential insight into the growth-inhibitory mechanisms of SBC3. Guided by the proteomic findings and the prolific biofilm and adherence capabilities of C. parapsilosis, our studies have shown the potential of SBC3 in reducing adherence to epithelial cells and biofilm formation and hence decrease fungal virulence

Safety of transanal ileal pouch-anal anastomosis for ulcerative colitis: a retrospective observational cohort study

Background: Colectomy with transanal ileal pouch-anal anastomosis (taIPAA) is a surgical technique that can be used to treat benign colorectal disease. Ulcerative colitis is the most frequent inflammatory bowel disease (IBD) and although pharmacological therapy has improved, colectomy rates reach up to 15%. The objective of this study was to determine anastomotic leakage rates and treatment after taIPAA as well as short- and long-term pouch function. Methods: We conducted a retrospective analysis of a prospective database of all patients undergoing taIPAA at an academic tertiary referral center in Germany, between 01/03/2015 and 31/08/2019. Patients with indications other than ulcerative colitis or with adjuvant chemotherapy following colectomy for colorectal carcinoma were excluded for short- and long-term follow up due to diverging postoperative care yet considered for evaluation of anastomotic leakage. Results: A total of 22 patients undergoing taIPAA during the study time-window were included in analysis. Median age at the time of surgery was 32 +/- 12.5 (14-54) years. Two patients developed an anastomotic leakage at 11 days (early anastomotic leakage) and 9 months (late anastomotic leakage) after surgery, respectively. In both patients, pouches could be preserved with a multimodal approach. Twenty patients out of 22 met the inclusion criteria for short and long term follow-up. Data on short-term pouch function could be obtained in 14 patients and showed satisfactory pouch function with only four patients reporting intermittent incontinence at a median stool frequency of 9-10 times per day. In the long-term we observed an inflammation or "pouchitis" in 11 patients and a pouch failure in one patient. Conclusion: Postoperative complication rates in patients with benign colorectal disease remain an area of concern for surgical patient safety. In this pilot study on 22 selected patients, taIPAA was associated with two patients developing anastomotic leakage. Future large-scale validation studies are required to determine the safety and feasibility of taIPAA in patients with ulcerative colitis

Continuous flow synthesis and antimicrobial evaluation of NHC* silver carboxylate derivatives of SBC3 in vitro and in vivo

N-heterocyclic silver carbene compounds have been extensively studied and shown to be active agents against a host of pathogenic bacteria and fungi. By incorporating hypothesized virulence targeting substituents into NHC–silver systems via salt metathesis, an atom-efficient complexation process can be used to develop new complexes to target the passive and active systems of a microbial cell. The incorporation of fatty acids and an FtsZ inhibitor have been achieved, and creation of both the intermediate salt and subsequent silver complex has been streamlined into a continuous flow process. Biological evaluation was conducted with in vitro toxicology assays showing these novel complexes had excellent inhibition against Gram-negative strains E. coli, P. aeruginosa, and K. pneumoniae; further studies also confirmed the ability to inhibit biofilm formation in methicillin-resistant Staphylococcus aureus (MRSA) and C. Parapsilosis. In vivo testing using a murine thigh infection model showed promising inhibition of MRSA for the lead compound SBC3, which is derived from 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*).European Commission - European Regional Development FundScience Foundation IrelandSchool of Chemistry & the College of Science of University College Dubli