Transport properties of individual C60-molecules.

Electrical and thermal transport properties of C60 molecules are investigated with density-functional-theory based calculations. These calculations suggest that the optimum contact geometry for an electrode terminated with a single-Au atom is through binding to one or two C-atoms of C60 with a tendency to promote the sp(2)-hybridization into an sp(3)-type one. Transport in these junctions is primarily through an unoccupied molecular orbital that is partly hybridized with the Au, which results in splitting the degeneracy of the lowest unoccupied molecular orbital triplet. The transmission through these junctions, however, cannot be modeled by a single Lorentzian resonance, as our results show evidence of quantum interference between an occupied and an unoccupied orbital. The interference results in a suppression of conductance around the Fermi energy. Our numerical findings are readily analyzed analytically within a simple two-level model.

Length-dependent thermopower of highly conducting Au-C bonded single molecule junctions.

We report the simultaneous measurement of conductance and thermopower of highly conducting single-molecule junctions using a scanning tunneling microscope-based break-junction setup. We start with molecular backbones (alkanes and oligophenyls) terminated with trimethyltin end groups that cleave off in situ to create junctions where terminal carbons are covalently bonded to the Au electrodes. We apply a thermal gradient across these junctions and measure their conductance and thermopower. Because of the electronic properties of the highly conducting Au-C links, the thermoelectric properties and power factor are very high. Our results show that the molecular thermopower increases nonlinearly with the molecular length while conductance decreases exponentially with increasing molecular length. Density functional theory calculations show that a gateway state representing the Au-C covalent bond plays a key role in the conductance. With this as input, we analyze a series of simplified models and show that a tight-binding model that explicitly includes the gateway states and the molecular backbone states accurately captures the experimentally measured conductance and thermopower trends.

Probing the conductance superposition law in single-molecule circuits with parallel paths.

According to Kirchhoff's circuit laws, the net conductance of two parallel components in an electronic circuit is the sum of the individual conductances. However, when the circuit dimensions are comparable to the electronic phase coherence length, quantum interference effects play a critical role, as exemplified by the Aharonov-Bohm effect in metal rings. At the molecular scale, interference effects dramatically reduce the electron transfer rate through a meta-connected benzene ring when compared with a para-connected benzene ring. For longer conjugated and cross-conjugated molecules, destructive interference effects have been observed in the tunnelling conductance through molecular junctions. Here, we investigate the conductance superposition law for parallel components in single-molecule circuits, particularly the role of interference. We synthesize a series of molecular systems that contain either one backbone or two backbones in parallel, bonded together cofacially by a common linker on each end. Single-molecule conductance measurements and transport calculations based on density functional theory show that the conductance of a double-backbone molecular junction can be more than twice that of a single-backbone junction, providing clear evidence for constructive interference.

Van der Waals interactions at metal/organic interfaces at the single-molecule level.

Van der Waals (vdW) interaction, and its subtle interplay with chemically specific interactions and surface roughness at metal/organic interfaces, is critical to the understanding of structure-function relations in diverse areas, including catalysis, molecular electronics and self-assembly. However, vdW interactions remain challenging to characterize directly at the fundamental, single-molecule level both in experiments and in first principles calculations with accurate treatment of the non-local, London dispersion interactions. In particular, for metal/organic interfaces, efforts so far have largely focused on model systems consisting of adsorbed molecules on flat metallic surfaces with minimal specific chemical interaction. Here we show, through measurements of single-molecule mechanics, that pyridine derivatives can bind to nanostructured Au electrodes through an additional binding mechanism beyond the chemically specific N-Au donor-acceptor bond. Using density functional theory simulations we show that vdW interactions between the pyridine ring and Au electrodes can play a key role in the junction mechanics. These measurements thus provide a quantitative characterization of vdW interactions at metal/organic interfaces at the single-molecule level.

Induced Regenerative Elastic Matrix Repair in LOXL1 Knockout Mouse Cell Cultures: Towards Potential therapy for Pelvic Organ Prolapse.

Impaired elastic matrix remodeling occurs in reproductive tissues after vaginal delivery. This has been linked to development of pelvic organ prolapse (POP) for which there currently is no pharmacologic therapy. Hyaluronan oligomers and transforming growth factor beta 1 (termed elastogenic factors, EFs) have been shown to significantly enhance tropoelastin synthesis, elastic fiber assembly, and crosslinking by adult vascular smooth muscle cells (SMCs). The goal of this study was to ascertain if these factors similarly improve the quantity and quality of elastic matrix deposition by vaginal SMCs (VSMCs) isolated from lysyl oxidase like-1 knock out (LOXL1 KO) mouse model of POP. Cells isolated from whole vagina of a LOXL1 KO mouse (multiparous, stage 3 prolapse) were cultured and identified as SMCs by their expression of various SMC markers. Passage 2 vaginal SMCs (VSMCs; 3×104/10 cm2) were cultured for 21 days with EFs. Cell layers and spent medium aliquots were assessed for elastin content and quality. EF-treated VSMCs proliferated at a similar rate to untreated controls but synthesized more total elastin primarily in the form of soluble matrix elastin. Elastin mRNA was also increased compared to controls. The elastic matrix was significantly denser in EF-treated cultures, which was composed of more mature, non-interrupted elastic fibers that were absent in controls. The results are promising towards development of a therapy to enhance regenerative elastic matrix repair in post-partum female pelvic floor tissues.

In situ formation of highly conducting covalent Au-C contacts for single-molecule junctions.

Charge transport across metal-molecule interfaces has an important role in organic electronics. Typically, chemical link groups such as thiols or amines are used to bind organic molecules to metal electrodes in single-molecule circuits, with these groups controlling both the physical structure and the electronic coupling at the interface. Direct metal-carbon coupling has been shown through C60, benzene and π-stacked benzene, but ideally the carbon backbone of the molecule should be covalently bonded to the electrode without intervening link groups. Here, we demonstrate a method to create junctions with such contacts. Trimethyl tin (SnMe(3))-terminated polymethylene chains are used to form single-molecule junctions with a break-junction technique. Gold atoms at the electrode displace the SnMe(3) linkers, leading to the formation of direct Au-C bonded single-molecule junctions with a conductance that is ∼100 times larger than analogous alkanes with most other terminations. The conductance of these Au-C bonded alkanes decreases exponentially with molecular length, with a decay constant of 0.97 per methylene, consistent with a non-resonant transport mechanism. Control experiments and ab initio calculations show that high conductances are achieved because a covalent Au-C sigma (σ) bond is formed. This offers a new method for making reproducible and highly conducting metal-organic contacts.

Environmental control of single-molecule junction transport.

The conductance of individual 1,4-benzenediamine (BDA)-Au molecular junctions is measured in different solvent environments using a scanning tunneling microscope based point-contact technique. Solvents are found to increase the conductance of these molecular junctions by as much as 50%. Using first principles calculations, we explain this increase by showing that a shift in the Au contact work function is induced by solvents binding to undercoordinated Au sites around the junction. Increasing the Au contact work function reduces the separation between the Au Fermi energy and the highest occupied molecular orbital of BDA in the junction, increasing the measured conductance. We demonstrate that the solvent-induced shift in conductance depends on the affinity of the solvent to Au binding sites and also on the induced dipole (relative to BDA) upon adsorption. Via this mechanism, molecular junction level alignment and transport properties can be statistically altered by solvent molecule binding to the contact surface.

Mechanics and chemistry: single molecule bond rupture forces correlate with molecular backbone structure.

We simultaneously measure conductance and force across nanoscale junctions. A new, two-dimensional histogram technique is introduced to statistically extract bond rupture forces from a large data set of individual junction elongation traces. For the case of Au point contacts, we find a rupture force of 1.4 ± 0.2 nN, which is in good agreement with previous measurements. We then study systematic trends for single gold metal-molecule-metal junctions for a series of molecules terminated with amine and pyridine linkers. For all molecules studied, single molecule junctions rupture at the Au-N bond. Selective binding of the linker group allows us to correlate the N-Au bond-rupture force to the molecular backbone. We find that the rupture force ranges from 0.8 nN for 4,4' bipyridine to 0.5 nN in 1,4 diaminobenzene. These experimental results are in excellent quantitative agreement with density functional theory based adiabatic molecular junction elongation and rupture calculations.

Relating energy level alignment and amine-linked single molecule junction conductance.

Using photoemission spectroscopy, we determine the relationship between electronic energy level alignment at a metal-molecule interface and single-molecule junction transport data. We measure the position of the highest occupied molecular orbital (HOMO) relative to the Au metal Fermi level for three 1,4-benzenediamine derivatives on Au(111) and Au(110) with ultraviolet and resonant X-ray photoemission spectroscopy. We compare these results to scanning tunnelling microscope-based break-junction measurements of single molecule conductance and to first-principles calculations. We find that the energy difference between the HOMO and Fermi level for the three molecules adsorbed on Au(111) correlate well with changes in conductance and agree well with quasiparticle energies computed from first-principles calculations incorporating self-energy corrections. On the Au(110) that presents Au atoms with lower-coordination, critical in break-junction conductance measurements, we see that the HOMO level shifts further from the Fermi level. These results provide the first direct comparison of spectroscopic energy level alignment measurements with single molecule junction transport data.

Conductance and geometry of pyridine-linked single-molecule junctions.

We have measured the conductance and characterized molecule-electrode binding geometries of four pyridine-terminated molecules by elongating and then compressing gold point contacts in a solution of molecules. We have found that all pyridine-terminated molecules exhibit bistable conductance signatures, signifying that the nature of the pyridine-gold bond allows two distinct conductance states that are accessed as the gold-molecule-gold junction is elongated. We have identified the low-conductance state as corresponding to a molecule fully stretched out between the gold electrodes, where the distance between contacts correlates with the length of the molecule; the high-conductance state is due to a molecule bound at an angle. For all molecules, we have found that the distribution of junction elongations in the low-conductance state is the same, while in the high-conductance state, the most likely elongation length increases linearly with molecule length. The results of first-principles conductance calculations for the four molecules in the low-conductance geometry agree well with the experimental results and show that the dominant conducting channel in the conjugated pyridine-linked molecules is through the pi* orbital.

Measurement of voltage-dependent electronic transport across amine-linked single-molecular-wire junctions.

We measure the conductance and current-voltage characteristics of two amine-terminated molecular wires -- 4,4'-diaminostilbene and bis-(4-aminophenyl)acetylene -- by breaking Au point contacts in a molecular solution at room temperature. Histograms compiled from thousands of measurements show a slight increase in the molecular junction conductance (I/V) as the bias is increased to nearly 450 mV. Comparatively, similar conductance measurements made with 1,6-diaminohexane, a saturated molecule, demonstrate almost no bias dependence. We also present a new technique to measure a statistically defined current-voltage (I-V) curve. Application to all three molecules shows that 4,4'-diaminostilbene exhibits the largest increase in differential conductance as a function of applied bias. This indicates that the predominant transport channel for 4,4'-diaminostilbene (the highest occupied molecular orbital) is closer to the Fermi level of the metal than that of the other molecules, consistent with the trends observed in the molecular ionization potential. We find that junctions constructed with the conjugated molecules show greater noise in individual junctions and less structural stability, on average, at biases greater than 450 mV. In contrast, junctions formed with the alkane can sustain a bias of up to 900 mV. This significantly affects the statistically averaged I-V characteristic measured for the conjugated molecules at higher bias.

Formation and evolution of single-molecule junctions.

We analyze the formation and evolution statistics of single-molecule junctions bonded to gold electrodes using amine, methyl sulfide, and dimethyl phosphine link groups by measuring conductance as a function of junction elongation. For each link, the maximum elongation and formation probability increase with molecular length, strongly suggesting that processes other than just metal-molecule bond breakage play a key role in junction evolution under stress. Density functional theory calculations of adiabatic trajectories show sequences of atomic-scale changes in junction structure, including shifts in the attachment point, that account for the long conductance plateau lengths observed.

Utility of peptide nucleic acid fluorescence in situ hybridization for rapid detection of Acinetobacter spp. and Pseudomonas aeruginosa.

The utility of peptide nucleic acid fluorescence in situ hybridization (PNA FISH) for the detection of Acinetobacter spp. and Pseudomonas aeruginosa was evaluated on broth suspensions and spiked blood cultures of ATCC strains and clinical isolates with select gram-negative rods. After testing 60 clinical isolates, PNA FISH had a sensitivity and specificity of 100% and 100%, respectively, for Acinetobacter spp. and 100% and 95%, respectively, for P. aeruginosa. PNA FISH was able to detect both pathogens simultaneously and directly from spiked blood cultures.

Methicillin-resistant Staphylococcus aureus bacteraemia diagnosed at hospital admission: distinguishing between community-acquired versus healthcare-associated strains.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections diagnosed at hospital admission are often referred to as community-acquired. This designation may include MRSA strains previously acquired in a healthcare setting (healthcare-associated) as well as those that have emerged from community-based S. aureus strains. METHODS: To understand further the epidemiology of MRSA from the community, a case-control study was performed. During 1997-2002, 254 patients with and without MRSA bacteraemia at hospital admission were studied. RESULTS: All patients with MRSA bacteraemia in the first 24 h of hospital admission had a recent exposure to a healthcare setting: true community-acquired MRSA was not detected. Independent risk factors for healthcare-associated MRSA bacteraemia, defined as MRSA bacteraemia in the first 24 h of hospital admission among patients with a recent exposure to a healthcare setting or intervention, included previous MRSA infection or colonization (OR = 17, P < 0.001), cellulitis (OR = 4, P = 0.006), presence of a central venous catheter (OR = 3, P < 0.001) and skin ulcers (OR = 3, P = 0.007). CONCLUSIONS: In this study, MRSA bacteraemia diagnosed in the first 24 h of hospital admission represented healthcare-associated MRSA strains and not true community-acquired strains. The clinical characteristics associated with healthcare-associated MRSA bacteraemia can assist clinicians in targeting measures to prevent cross-transmission and may help to streamline empirical vancomycin therapy.

Methicillin-resistant Staphylococcus aureus: comparison of susceptibility testing methods and analysis of mecA-positive susceptible strains.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for an increasing number of serious nosocomial and community-acquired infections. Phenotypic heterogeneous drug resistance (heteroresistance) to antistaphylococcal beta-lactams affects the results of susceptibility testing. The present study compared the MRSA-Screen latex agglutination test (Denka Seiken Co., Ltd., Tokyo, Japan) for detection of PBP 2a with agar dilution, the VITEK-1 and VITEK-2 systems (bioMérieux, St. Louis, Mo.), and the oxacillin agar screen test for detection of MRSA, with PCR for the mecA gene used as the "gold standard" assay. Analysis of 107 methicillin-susceptible S. aureus (MSSA) isolates and 203 MRSA isolates revealed that the MRSA-Screen latex agglutination test is superior to any single phenotype-based susceptibility testing method, with a sensitivity of 100% and a specificity of 99.1%. Only one isolate that lacked mecA was weakly positive by the MRSA-Screen latex agglutination test. This isolate was phenotypically susceptible to oxacillin and did not contain the mecA gene by Southern blot hybridization. The oxacillin agar screen test, the VITEK-1 system, the VITEK-2 system, and agar dilution showed sensitivities of 99.0, 99.0, 99.5, and 99%, respectively, and specificities of 98.1, 100, 97.2, and 100%, respectively. The differences in sensitivity or specificity were not statistically significant. Oxacillin bactericidal assays showed that mecA- and PBP 2a-positive S. aureus isolates that are susceptible to antistaphylococcal beta-lactams by conventional methods are functionally resistant to oxacillin. We conclude that the accuracy of the MRSA-Screen latex agglutination method for detection of PBP 2a approaches the accuracy of PCR and is more accurate than any susceptibility testing method used alone for the detection of MRSA.

Growth performance of two Indian major carps, catla (Catla catla) and rohu (Labeo rohita) fed diets containing different levels of Spirulina platensis.

The influence of Spirulina platensis meal on the growth and carcass composition of two Indian major carps, catla, Catla catla and rohu, Labeo rohita was investigated in a 90-day culture trial. Four experimental diets were used and Spirulina replaced fish meal protein from the standard diet at 25%, 50%, 75% and 100% levels. There was no significant difference in the final weight attained by catla at all levels of Spirulina incorporation as compared to the fish-meal-based control diet. However, the replacement of fish meal by more than 25% Spirulina resulted in significantly superior growth of rohu. The specific growth rate and protein efficiency ratio recorded in rohu improved with higher levels of Spirulina inclusion, while in catla they did not differ significantly from the control treatment. In both the species, the digestibility of dry matter, protein and fat was found to improve marginally with increasing levels of Spirulina incorporation. The carcass composition showed an inverse relationship between protein and fat deposition. In general, fish fed with Spirulina diets had a significantly higher percentage of fat. The study demonstrated the usefulness of Spirulina for partial or complete replacement of fish meal in the diets of catla and rohu.

Morphological and functional characteristics of rabbit uterine epithelial cells grown on free floating collagen gel.

In the present study isolated uterine epithelial cells from normal rabbits were maintained in culture on free floating rat-tail collagen matrix, and the morphological characteristics of these cells were examined. Additionally, the pattern of protein synthesis and secretion by rabbit uterine epithelial cells grown on free floating collagen gels following estradiol and/or progesterone treatment in vitro was examined. Isolated epithelial cells cultured on collagen gels in complete medium containing serum attached to form monlayers, and eventually the gels became free floating and contracted giving rise to luminal arrangements. These cells were cytokeratin positive epithelial cells and were ultrastructurally polarized. These cells also exhibited differential upregulation and down regulation in the synthesis and secretion of proteins in response to estradiol, progesterone, and estradiol plus progesterone. Additionally, a permissive action between progesterone and estradiol in the synthesis of two species of secretory proteins was observed. It however remains to be examined whether different species of proteins produced in vitro in response to estradiol and progesterone bear any association with physiological states in reproductive cycle in this species.

Linezolid resistance in a clinical isolate of Staphylococcus aureus.

The new oxazolidinone antimicrobial, linezolid, has been approved for the treatment of infections caused by various gram-positive bacteria, including meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Although instances of linezolid resistance in VRE have been reported, resistance has not been encountered among clinical isolates of S aureus. We have characterised an MRSA isolate resistant to linezolid that was recovered from a patient treated with this agent for dialysis-associated peritonitis.

Molecular typing of coagulase-negative staphylococci from blood cultures does not correlate with clinical criteria for true bacteremia.

PURPOSE: Determining whether a blood culture that contains coagulase-negative staphylococci represents bacteremia or contamination is a clinical dilemma. We compared molecular-typing results of coagulase-negative staphylococcal blood culture isolates with clinical criteria for true bacteremia. SUBJECTS AND METHODS: Pulsed-field gel electrophoresis and arbitrary primed polymerase chain reaction (PCR) were used to determine whether patients with two or more blood cultures with coagulase-negative staphylococcal isolates had the same strain of organism in each culture (same strain bacteremia). We evaluated three different clinical criteria for bacteremia: whether the patient received more than 4 days of antibiotics, whether there was an explicit note in the medical chart in which the physician diagnosed a true bacteremia, and the Centers for Disease Control surveillance criteria for primary bloodstream infection. Agreement between same-strain bacteremia and each definition was examined, based on the assumption that most true infections should be the result of a single strain. RESULTS: The study sample consisted of 42 patients and 106 isolates. Nineteen of the 42 bacteremias (45%) were the same strain. Classification of bacteremias as same-strain correlated poorly with all three clinical assessments (range of percent agreement, 50% to 57%; range of kappa statistic, 0.01 to 0.15). There were both false-positive and false-negative errors. Patients with three or more positive blood cultures were more likely to have same-strain bacteremia than those with only two positive cultures [11 of 15 (73%) vs 8 of 27 (30%), P = 0.006]. Pulsed-field gel electrophoresis was more discriminating than arbitrary primed PCR (percent agreement, 83%; kappa, 0.67). CONCLUSION: Molecular typing correlated poorly with clinical criteria for true bacteremia, suggesting either that true bacteremias are frequently the result of multiple strains or that the commonly used clinical criteria are not accurate for distinguishing contamination from true bacteremia. Vancomycin treatment of clinically defined coagulase-negative staphylococcal bacteremia may frequently be unnecessary.

A cluster of VanD vancomycin-resistant Enterococcus faecium: molecular characterization and clinical epidemiology.

VanD-mediated glycopeptide resistance has been reported for an isolate of Enterococcus faecium, BM4339. Three clinical isolates of vancomycin-resistant E. faecium collected from 3 patients during a 6-week period in 1993 had agar dilution MICs of vancomycin and teicoplanin of 128 and 4 microg/mL, respectively. Polymerase chain reaction (PCR) using degenerate primers complementary to genes encoding d-Ala-d-X ligases yielded a 630-bp product that was similar to the published partial sequence of vanD. By use of inverse PCR, vanD, vanHD, and two partial flanking open-reading frames were sequenced. The deduced amino acid sequence of VanD showed 67% identity with VanA and VanB. vanD appeared to be located on the chromosome and was not transferable to other enterococci. The 3 isolates were indistinguishable by pulsed-field gel electrophoresis and differed from BM4339. No other isolates carrying vanD were found in a subset of 875 recent US isolates of vancomycin-resistant enterococci.