Synthesis of armchair graphene nanoribbons from the 10,10'-dibromo-9,9'-bianthracene molecules on Ag(111): the role of organometallic intermediates.

We investigate the bottom-up growth of N = 7 armchair graphene nanoribbons (7-AGNRs) from the 10,10'-dibromo-9,9'-bianthracene (DBBA) molecules on Ag(111) with the focus on the role of the organometallic (OM) intermediates. It is demonstrated that DBBA molecules on Ag(111) are partially debrominated at room temperature and lose all bromine atoms at elevated temperatures. Similar to DBBA on Cu(111), debrominated molecules form OM chains on Ag(111). Nevertheless, in contrast with the Cu(111) substrate, formation of polyanthracene chains from OM intermediates via an Ullmann-type reaction is feasible on Ag(111). Cleavage of C-Ag bonds occurs before the thermal threshold for the surface-catalyzed activation of C-H bonds on Ag(111) is reached, while on Cu(111) activation of C-H bonds occurs in parallel with the cleavage of the stronger C-Cu bonds. Consequently, while OM intermediates obstruct the Ullmann reaction between DBBA molecules on the Cu(111) substrate, they are required for the formation of polyanthracene chains on Ag(111). If the Ullmann-type reaction on Ag(111) is inhibited, heating of the OM chains produces nanographenes instead. Heating of the polyanthracene chains produces 7-AGNRs, while heating of nanographenes causes the formation of the disordered structures with the possible admixture of short GNRs.

Surface-confined Ullmann coupling of thiophene substituted porphyrins.

The covalent coupling of (5,10,15,20-tetrabromothien-2-ylporphyrinato)zinc(II) (TBrThP) molecules on the Ag(111) surface has been investigated under ultra-high-vacuum conditions, using scanning tunnelling microscopy and x-ray photoelectron spectroscopy. The findings provide atomic-level insight into surface-confined Ullmann coupling of thiophene substituted porphyrins, analyzing the progression of organometallic intermediate to final coupled state. Adsorption of the TBrThP molecules on the Ag(111) surface at room temperature is found to result in the reductive dehalogenation of the bromothienyl substituents and the subsequent formation of single strand and crosslinked coordination networks. The coordinated substrate atoms bridge the proximal thienyl groups of the organometallic intermediate, while the cleaved bromine atoms are bound on the adjacent Ag(111) surface. The intermediate complex displays a thermal lability at ∼423 K that results in the dissociation of the proximal thienyl groups with the concomitant loss of the surface bound bromine. At the thermally induced dissociation of the intermediate complex the resultant thienylporphyrin derivatives covalently couple, leading to the formation of a polymeric network of thiophene linked and meso-meso fused porphyrins.

The antimicrobial effects of helium and helium-air plasma on Staphylococcus aureus and Clostridium difficile.

UNLABELLED: Healthcare-associated infections (HCAI) affect 5-10% of acute hospital admissions. Environmental decontamination is an important component of all strategies to prevent HCAI as many bacterial causes survive and persist in the environment, which serve as ongoing reservoirs of infection. Current approaches such as cleaning with detergents and the use of chemical disinfectant are suboptimal. We assessed the efficacy of helium and helium-air plasma in killing Staphylococcus aureus and Clostridium difficile on a glass surface and studied the impact on bacterial cells using atomic force microscopy (AFM). Both plasma types exhibited bactericidal effects on Staph. aureus (log3·6 - >log7), with increased activity against methicillin-resistant strains, but had a negligible effect on Cl. difficile spores (<1log). AFM demonstrated cell surface disruption. The addition of air increased the microbicidal activity of the plasma and decreased the exposure time required for an equivalent log reduction. Further evaluation of cold plasma systems is warranted with, for example, different bacteria and on surfaces more reminiscent of the health care environment as this approach has potential as an effective decontaminant. SIGNIFICANCE AND IMPACT OF THE STUDY: Many bacterial causes of healthcare infection can survive in the inanimate environment for lengthy periods and be transmitted to patients. Furthermore, current methods of environmental decontamination such as detergents, chemical disinfectants or gaseous fumigation are suboptimal for a variety of reasons. We assessed the efficacy of helium and helium-air plasma as a decontaminant and demonstrated a significant reduction in bacterial counts of Staphylococcus aureus on a glass surface. Atomic force microscopy morphologically confirmed the impact on bacterial cells. This approach warrants further study as an alternative to current options for hospital hygiene.

Control of the axial coordination of a surface-confined manganese (III) porphyrin complex.

The organization and thermal lability of chloro(5,10,15,20-tetraphenyl porphyrinato)manganese(III) (Cl-MnTPP) molecules on the Ag(111) surface have been investigated under ultra-high vacuum conditions, using scanning tunnelling microscopy, low energy electron diffraction and x-ray photoelectron spectroscopy. The findings reveal the epitaxial nature of the molecule-substrate interface, and moreover, offer a valuable insight into the latent coordination properties of surface-confined metalloporphyrins. The Cl-MnTPP molecules are found to self-assemble on the Ag(111) surface at room temperature, forming an ordered molecular overlayer described by a square unit cell. In accordance with the threefold symmetry of the Ag(111) surface, three rotationally equivalent domains of the molecular overlayer are observed. The primitive lattice vectors of the Cl-MnTPP overlayer show an azimuthal rotation of ±15° relative to those of the Ag(111) surface, while the principal molecular axes of the individual molecules are found to be aligned with the substrate (0(-)11) and ((-)211) crystallographic directions. The axial chloride (Cl) ligand is found to be orientated away from the Ag(111) surface, whereby the average plane of the porphyrin macrocycle lies parallel to that of the substrate. When adsorbed on the Ag(111) surface, the Cl-MnTPP molecules display a latent thermal lability resulting in the dissociation of the axial Cl ligand at ~423 K. The thermally induced dissociation of the Cl ligand leaves the porphyrin complex otherwise intact, giving rise to the coordinatively unsaturated Mn(III) derivative. Consistent with the surface conformation of the Cl-MnTPP precursor, the resulting (5,10,15,20-tetraphenyl porphyrinato)manganese(III) (MnTPP) molecules display the same lattice structure and registry with the Ag(111) surface.

Growth and ordering of Ni(II) diphenylporphyrin monolayers on Ag(111) and Ag/Si(111) studied by STM and LEED.

The room temperature self-assembly and ordering of (5,15-diphenylporphyrinato)nickel(II) (NiDPP) on the Ag(111) and Ag/Si(111)-(√3 × âˆš3)R30° surfaces have been investigated using scanning tunnelling microscopy and low-energy electron diffraction. The self-assembled structures and lattice parameters of the NiDPP monolayer are shown to be extremely dependent on the reactivity of the substrate, and probable molecular binding sites are proposed. The NiDPP overlayer on Ag(111) grows from the substrate step edges, which results in a single-domain structure. This close-packed structure has an oblique unit cell and consists of molecular rows. The molecules in adjacent rows are rotated by approximately 17° with respect to each other. In turn, the NiDPP molecules form three equivalent domains on the Ag/Si(111)-(√3 × âˆš3)R30° surface, which follow the three-fold symmetry of the substrate. The molecules adopt one of three equivalent orientations on the surface, acting as nucleation sites for these domains, due to the stronger molecule-substrate interaction compared to the case of the Ag(111). The results are explained in terms of the substrate reactivity and the lattice mismatch between the substrate and the molecular overlayer.

"Zeus" a new oral anticoagulant therapy dosing algorithm: a cohort study.

The demand for oral anticoagulant therapy (OAT) has constantly increased during the last ten years with an extended use of computer assistance. Many mathematical algorithms have been projected to suggest doses and time to next visit for patients on OAT. We designed a new algorithm: "Zeus". A "before-after" study was planned to compare the efficacy and safety of this algorithm dosing OAT with manual dosage decided by the same expert physicians according to the target of International Normalized Ratio (INR). The study analysed data of 1876 patients managed with each of the two modalities for eight months, with an interval of two years between them. The aim was to verify the increased quality of therapy by time spent in INR target and efficiency and safety of Zeus algorithm. Time in therapeutic range (TTR) was significantly (p < 0.0001) higher during the algorithm dosing period in comparison with the TTR during manual management period (62.3% vs 50.3%). The number of PT/INR tests above 5 was significantly (p < 0.001) reduced by algorithm suggested prescriptions in comparison with manual those (254 vs 537 times). The anticoagulant drug amount prescribed according to the algorithm suggestions was significantly (p < 0.0001) lower than that of the manual method. The number of clinical events observed in patients during the algorithm management time was significantly (p < 0.05) lower than that in those managed with the manual dosage. This study confirms the clinical utility of the computer-assisted OAT and shows the efficacy and safety of the Zeus algorithm.

Reactive amine surfaces for biosensor applications, prepared by plasma-enhanced chemical vapour modification of polyolefin materials.

Here we have demonstrated a solventless plasma-based process that integrates low-cost, high throughput, high reproducibility and ecofriendly process for the functionalization of the next-generation point-of-care device platforms. Amine functionalities were deposited by plasma-enhanced chemical vapour deposition (PECVD) using a new precursor. The influence of the plasma RF power and the deposition time on surfacial properties, as well as their effect on the reactivity and content of amino groups was investigated. The key process determinants were to have a sufficient power in the plasma to activate and partially fragment the monomer but not too much as to lose the reactive amine functionality, and sufficient deposition time to develop a reactive layer but not to consume or erode the amine reactivity. An immunoassay performed using human immunoglobulin (IgG) as a model analyte showed an improvement of the detection limit by two orders of magnitude beyond that obtained using devices activated by liquid-phase reaction.

Protein pattern transfer for biosensor applications.

This paper presents a very simple, industrially scalable method for transferring a high-resolution, biologically active protein pattern from one substrate to another. We demonstrate the transfer of a protein pattern formed initially by microcontact printing from a silicon surface (to which this form of printing is applicable) onto a glass or polymer substrate, almost independently of the surface/bulk properties of the second substrate. A very thin, spin-coated layer of a sugar is used to preserve the structure and organization of proteins during the subsequent plasma deposition of a siloxane polymer, after which the protein pattern could simply be peeled off the silicon substrate and glued onto any other desired substrate.

Ni(II) porphine nanolines grown on a Ag(111) surface at room temperature.

The room temperature growth and ordering of (porphyrinato)nickel (II) (or nickel (II) porphine, NiP) molecules on a Ag(111) surface have been investigated using scanning tunnelling microscopy and low-energy electron diffraction (LEED). At a coverage of one monolayer, NiP molecules form a well-ordered molecular layer, having a hexagonal structure, on the Ag(111) surface. Porphyrin molecules have a flat orientation in this overlayer with the molecular plane lying parallel to the substrate. LEED data obtained from one monolayer of the NiP on the Ag(111) surface show the formation of two mirror domains each rotated either clockwise or anticlockwise by 6 degrees with respect to the substrate. NiP molecules forming a second layer self-assemble into well-ordered and uniformly separated nanolines at room temperature. These nanolines consist of hexagonally ordered NiP molecules and are found to be 1-4 molecules wide, depending on the molecular coverage. The completed second monolayer preserves the same planarity and hexagonal ordering as the first molecular layer but with a 4% lateral relaxation which produces a periodic modulation of approximately 5 nm.

An x-ray absorption and photoemission study of the electronic structure of Ni porphyrins and Ni N-confused porphyrin.

Investigations of chemical bonding and electronic structure features for polycrystalline (porphyrinato)nickel (II) (NiP, the simplest Ni porphyrin), (5,10,15,20-tetraphenylporphyrinato)nickel (II) (NiTPP) and (2-aza-21-carba-5,10,15,20-tetraphenylporphyrinato)nickel (II) (N-confused NiTPP, NiNCTPP) have been performed by means of high-resolution soft x-ray absorption and x-ray photoemission spectroscopy. The Ni 2p(3/2) x-ray absorption spectra show strong π-back-bonding in these compounds leading to a high-energy shift (1.2 eV for the NiP and NiTPP) of the entire absorption structure compared to Ni metal. It has been found that the main absorption line of the Ni 2p(3/2) spectrum of the NiNCTPP is shifted by an additional 0.5 eV to higher energies in comparison with those for other nickel porphyrins. This shift is evidence of stronger back-donation (metal-to-ligand charge transfer) and a smaller effective number of 3d electrons on the central Ni atom in the NiNCTPP as compared to other Ni porphyrins. The confused N atom in the NiNCTPP is of pyrrolic type (protonated nitrogen), which was confirmed by the N 1s absorption and core-level photoemission spectra.

The dominant role of adsorbed fluid layers on the polar surfaces of ZnO in ambient atmospheric conditions.

Polar ZnO surfaces with O- and Zn-termination were studied with atomic and lateral force microscopy and force curves. Adsorbed fluid layers on both surfaces are found to dominate their adhesion properties in air. The hydrophilic O-surface has a substantially thicker adsorbed layer and larger residual particle densities. Our data suggest that different preparation is required for the two surfaces before use in epitaxy, and may resolve some contradictions in the literature. The data also indicate that adsorbed fluid layers may be important in the growth of certain ZnO nanostructures.

Folate status, metabolic genotype, and biomarkers of genotoxicity in healthy subjects.

Gene-environment interactions play an important role in folate metabolism, with a potential impact on human health. Deficiencies in the uptake of key micronutrients and variant genotypes can affect the folic acid cycle, modulating methyl group transfer in key processes and leading to increased cancer risk and Down syndrome incidence. So far, the significance of folate status and metabolic genotypes on baseline levels of DNA damage in normal individuals has not been fully elucidated. In this study, the possible modulation of SCE, micronuclei and tail moment values in peripheral lymphocytes by plasma levels of folic acid, homocysteine and vitamin B12, and by the methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms was investigated in 191 healthy subjects. The results obtained show a highly significant (P = 0.001) positive association between plasma levels of vitamin B12 and frequencies of both SCE and high frequency cells (HFC, above 90 degrees percentile) in smokers. No significant effect was observed in non-smokers. Moreover, after correction for age, gender and GSTM1 genotype, a significant association (P = 0.026) between the MTRR 66GG variant genotype and higher micronucleus rates was observed. Tail moment values were not affected by any of the independent variables considered. Overall, the results obtained suggest that both folate status and relevant metabolic genotype can influence background levels of DNA damage in normal subjects. The significant association observed in smokers between plasma vitamin B12 and SCE frequencies may highlight the effect of methylation status on DNA damage and repair, although the role of other, unidentified dietary factors cannot be ruled out. At the same time, micronucleus data indicate that the MTRR 66GG variant may represent another individual trait of relative genomic instability, thus supporting epidemiological data on increased risk of Down syndrome conception in MTRR 66GG subjects.

Lymphocyte T subsets and natural killer cells in Italian and Philippino blood donors.

BACKGROUND AND OBJECTIVES: The characterization of lymphocyte subsets in blood donors has been utilized to determine the normal ranges that can be related to race. A study was performed in blood donors from two racial groups - Caucasian (Italians) and Asian (Philippinos) - to define respective T-lymphocyte subsets and levels of cytokines. MATERIALS AND METHODS: Ninety-two blood donors (46 Italians and 46 Philippinos) were enrolled. Blood count and immunophenotyping of lymphocytes by flow cytometry were carried out, and cytokine production was tested in six blood donors of each group. RESULTS: Philippino blood donors showed a significantly higher mean value of leucocytes (P = 0.01) and lymphocytes (P < 0.001) than Italians. The mean absolute count of lymphocyte subsets CD3- CD16+ CD56+ and CD3+ CD8+ were both significantly higher in Philippino than in Italian subjects, respectively, P < 0.01 and P < 0.0001. Philippinos showed a statistically significant higher frequency of lymphocytes producing interferon-gamma (IFN-gamma) compared to Italians (P = 0.02). CONCLUSIONS: T-lymphocyte subsets in Italian and Philippino blood donors seem to be correlated to ethnic background. The higher levels of CD3+ CD8+ T cells, natural killer (NK) cells and IFN-gamma-producing cells found in Philippinos suggest leucoreduction in Asian blood donors.

Effect of folic acid and vitamin C supplementation on folate status and homocysteine level: a randomised controlled trial in Italian smoker-blood donors.

BACKGROUND: This trial sought to examine the effects of high dosage of folic acid and vitamin C supplementation on red blood cell folate (RCF), serum folate (SF) and homocysteine (Hcy) levels in subjects who smoke more than 15 cigarettes per day. METHODS: A prospective study of 100 Italian repeat blood donors was undertaken to measure RCF, SF and Hcy levels before and after 45 days of vitamin supplementation. All subjects were randomised into four groups: [A] folic acid (FA) 5 mg/day, [B] vitamin C 500 mg/day, [C] FA 5 mg/day plus vitamin C 500 mg/day [D] no supplementation. RESULTS: Before supplementation the median RCF, SF and Hcy levels were similar in the four groups; 32 (40%) subjects had an RCF level below 340 nmol/l, 15 (18.8%) had an SF level below 6.8 nmol/l and 21 (26.3%) had an Hcy level above 16 micromol/l. After 45 days the median RCF and SF levels were significantly (P<0.01) increased in all supplemented subjects. The median Hcy level was significantly (P=0.008) reduced in subjects supplemented with FA and significantly (P=0.01) increased in those supplemented with vitamin C alone. CONCLUSION: The supplementation with 5 FA mg/day is able to increase significantly both RCF and SF levels and reduce Hcy level in Italian smoker-blood donors.

High dose of idarubicin-based regimen for diffuse large cell AIDS-related non-Hodgkin's lymphoma patients: a pilot study.

BACKGROUND AND OBJECTIVES: Intensive chemotherapy (CHT) in AIDS-related non-Hodgkin's lymphoma (AIDS-NHL patients) is a vexing problem. Our purpose was to evaluate the feasibility of a high dose idarubicin (HD-IDA)-based regimen in diffuse large cell (DLC) AIDS-NHL patients. DESIGN AND METHODS: Fourteen stage I-IV untreated DLC AIDS-NHL patients with a performance status <3 and no prior AIDS-related diseases received CIOD: cyclophosphamide, HD-IDA (25 mg/m2 in 8 patients, 20 mg/m2 in 6 patients) vincristine and dexamethasone plus granulocyte colony-stimulating factor (G-CSF) and prophylaxis against infections. The outcomes measured were: rate of response, disease-free survival (DFS), overall survival (OS) and the impact of chemotherapy on immunologic and virological parameters. RESULTS: Complete response was achieved in 13/14 cases (response rate: 93%). The median time of response and survival was 33 (range 5-79) and 35.5 (range 6-84) months, respectively. At 60 months the DFS and OS were 71% and 44%, respectively. CIOD with idarubicin 20 mg/m2 was better tolerated than that with 25 mg/m2 and was administered with a higher mean average-relative-dose-intensity (95.38+/-7% vs 83.35+/-15.59%, p=0.0001). Opportunistic infections were more frequent in patients with a baseline CD4 <100 than those with >100 cells/microL (4/5 vs 1/9: p=0.0229). After 3 CIOD courses the mean CD4 cells/microL was significantly lower (p=0.001) and the mean HIV.1 RNA load was significantly higher (p=0.045) than at baseline. INTERPRETATION AND CONCLUSIONS: The proposed chemotherapeutic regimen for AIDS-related non-Hodgkin's lymphoma is feasible in an outpatient setting in selected patients with relatively well-preserved immune function.

Folate status in Italian blood donors: relation to gender and smoking.

BACKGROUND AND OBJECTIVES: Folate deficiency in the general population is associated with a risk of cardiovascular disease and various cancers. The aim of this study was to evaluate folate status in Italian blood donors and its relationship with gender and smoking habit. DESIGN AND METHODS: A prospective study of 201 first visit donors (99 males and 102 females) was undertaken to evaluate folate status by measuring serum folate (SF) and red blood cell folate (RCF) levels and relating those with gender and smoking habit (100 smokers and 101 non-smokers). RESULTS: The rates of SF level less than 6.8 nmol/L and RCF less than 340 nmol/L were 9.9% and 25.3%, respectively in Italian blood donors. Mean RCF level was significantly lower (p<0.05) in females than in males and in smokers compared to non-smokers (p<0.001). The risk of reduced RCF levels in smokers was related to the number of cigarettes smoked per day, more than nine cigarettes increased the relative risk (RR) of low RCF level to 2.93 (95% C.I.: 1.34-6.41). INTERPRETATION AND CONCLUSIONS: This study suggests that folate deficiency, evaluated by RCF and SF levels, is widespread in Italian blood donors. Moreover, RCF values seem related to gender in non-smokers and modified by smoking habit, according to the cigarettes number smoked per day.

HIV-HCV RNA loads and liver failure in coinfected patients with coagulopathy.

BACKGROUND AND OBJECTIVE: The aim of this study was to measure contemporaneously HCV-RNA load, HIV-RNA load and CD4+ lymphocyte count in HCV/HIV coinfected patients with coagulopathy and to examine the relationship between these parameters and the liver failure. DESIGN AND METHODS: A cross-sectional study was performed on 54 patients with severe coagulopathy: 39 HCV/HIV coinfected and 15 HCV+/HIV- comparable for age and HCV exposure time. HCV-RNA and HIV-RNA load, CD4+ lymphocyte count, biochemical and ultrasonographic parameters were evaluated at the time of entry to the study. RESULTS: Mean HCV-RNA load was significantly higher in coinfected patients (643,872 717,687 copies/mL) than in HCV+/HIV- (mean 161,573 276,896 copies/mL) (p = 0.01). The 39 HCV/HIV coinfected patients had a mean HIV-RNA load of 205,913 456,311 copies/mL (range 4,000-2,500,000) and a mean CD4+ lymphocyte count of 206.5171/microL (range 5-693). Five of the 39 (12.8%) coinfected patients had liver failure. In these five patients the mean HCV-RNA load (770,200 996,426 copies/mL) was high but not significantly different from that in the 34 HCV+/HIV+ patients (623,496 682,239 copies/mL) without liver failure (p = 1.0). Coinfected patients with liver failure had a significantly higher HIV-RNA load (mean 764, 599 978,542 copies/mL) and lower CD4+ lymphocyte count (mean 52.655. 6/microL) than those observed in coinfected patients without liver failure (p = 0.007 and p = 0.03, respectively). A significant inverse correlation was found between CD4+ lymphocyte count and HIV-RNA load (r = -0.37, p = 0.01). INTERPRETATION AND CONCLUSIONS: HCV-RNA load is significantly higher in HIV+ than in HIV- patients with coagulopathy. Liver failure was found only in the HCV/HIV coinfected patients with severe immunodepression, expressed either by low CD4+ lymphocyte count or by high HIV-RNA load.

Red cell folate in elderly patients with myelodysplastic syndrome.

During a 7-month period a prospective study of 71 anaemic patients (29 males and 42 females) over the age of 50 was undertaken in order to identify patients with myelodysplastic syndrome (MDS). The mean values of mean corpuscular volume (MCV), serum ferritin, folate, vitamin B12 and red cell folate (RCF) of patients grouped according to the diagnosis were compared to those observed in age-matched blood donors. Forty-four of the 71 elderly patients showed macrocytic anaemia: 21 of them had gastric disease and the remaining 23 MDS. Two further patients with MDS showed microcytic anaemia. The 25 patients diagnosed with MDS were subclassified according to the FAB nomenclature: 9 had a refractory anaemia with excess of blasts and 16 refractory anaemia. The mean values of MCV, serum folate, ferritin, vitamin B12 and RCF were statistically different between patients with macrocytic anaemia due to gastric disease and patients with MDS. Among patients with MDS, the RCF level pathologically high was inversely correlated to the haemoglobin level (r=-0.39; p<0.05). Thus the RCF and serum folate may represent useful parameters for the diagnosis of MDS in elderly anaemic patients.