First-principles simulations of the initial phase of self-aggregation of a cyanine dye: structure and optical spectra.

Using first-principles simulations, we investigated the initial steps of the self-aggregation of the dye pseudoisocyanine (PIC) in water. First, we performed molecular dynamics (MD) simulations of the self-aggregation process, in which pile-of-coins oligomers ranging from dimers to stacks of about 20 molecules formed. The oligomer structures were found to be very flexible, with the dimers entering a weakly coupled state and then returning to a stable π-π stacked conformation on a nanosecond time scale. The structural information from the MD simulations was combined with quantum chemical calculations to generate a time-dependent Frenkel exciton Hamiltonian for monomers, dimers, and trimers, which included vibronic coupling. This Hamiltonian, in turn, was used to calculate the absorption spectra for these systems. The simulated dimer spectrum compared well to experiment, validating the face-to-face stacked dimer arrangement found in our MD simulations. Comparison of the simulated trimer spectrum to experiment suggested that oligomers larger than the dimer cannot be abundant at the onset of J-aggregation. Finally, the conformation of the PIC J-aggregate was investigated by testing the stability of several possible conformations in our MD simulations; none of the tested structures was found to be stable.

First-principles calculation of the optical properties of an amphiphilic cyanine dye aggregate.

Using a first-principles approach, we calculate electronic and optical properties of molecular aggregates of the dye amphi-pseudoisocyanine, whose structures we obtained from molecular dynamics (MD) simulations of the self-aggregation process. Using quantum chemistry methods, we translate the structural information into an effective time-dependent Frenkel exciton Hamiltonian for the dominant optical transitions in the aggregate. This Hamiltonian is used to calculate the absorption spectrum. Detailed analysis of the dynamic fluctuations in the molecular transition energies and intermolecular excitation transfer interactions in this Hamiltonian allows us to elucidate the origin of the relevant time scales; short time scales, on the order of up to a few hundreds of femtoseconds, result from internal motions of the dye molecules, while the longer (a few picosecond) time scales we ascribe to environmental motions. The absorption spectra of the aggregate structures obtained from MD feature a blue-shifted peak compared to that of the monomer; thus, our aggregates can be classified as H-aggregates, although considerable oscillator strength is carried by states along the entire exciton band. Comparison to the experimental absorption spectrum of amphi-PIC aggregates shows that the simulated line shape is too wide, pointing to too much disorder in the internal structure of the simulated aggregates.

Investigating the structure of aggregates of an amphiphilic cyanine dye with molecular dynamics simulations.

We perform molecular dynamics (MD) simulations of the self-assembly process of pseudoisocyanine dye molecules with amphiphilic substituents (amphi-PIC). The spontaneous aggregation of cyanine molecules into large molecular J-aggregates with optical functionality has drawn attention for many decades already, but the shape and molecular structure of the aggregates remain issues of debate, as current imaging techniques still lack molecular scale resolution. Our MD simulations for amphi-PIC predict the existence of aggregates with the shape of either a single-walled cylinder or a ribbon. We characterize the internal structure of these aggregates using the π-π stacking and the average orientation of the long axis of the amphi-PIC molecule's chromophore. The molecular arrangement obtained exhibits much disorder, which may explain the wide absorption band observed for aggregates of amphi-PIC. We show that changing the counterion of the positively charged amphi-PIC dye can change the equilibrium aggregate shape. In addition, we demonstrate that the cylindrical aggregates attract each other and form bundles.

Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2004: a report of the Australian Mycobacterium Reference Laboratory Network.

The Australian Mycobacterium Reference Laboratory Network collected and analysed laboratory data on new cases of disease caused by Mycobacterium tuberculosis complex in the year 2004. A total of 787 cases were identified by bacteriology, representing an annual reporting rate of 3.9 cases per 100,000 population. Almost all isolates were identified as M. tuberculosis (n = 785), the remaining isolates being one each of Mycobacterium africanum and Mycobacterium canettii. Seven children under 10 years of age (female n = 5, male n = 2) had bacteriologically confirmed tuberculosis (gastric aspirate n = 4, lymph node n = 1, pleural n = 1, thigh wound n = 1). Results of in vitro drug susceptibility testing were available for all 787 isolates for isoniazid (H), rifampicin (R), ethambutol (E), and pyrazinamide (Z). A total of 71 (9.0%) isolates of M. tuberculosis were resistant to at least one of these anti-tuberculosis agents. Resistance to at least both H and R (defined as multidrug resistance) was detected in 12 (1.5%) isolates; 10 were from the respiratory tract (sputum n = 7, bronchoscopy n = 3). The country of birth was known for 68/71 (95.8%) cases with a drug resistant strain; eight were Australian, 60 were overseas born, and three were unknown. Of the 60 migrants with drug resistant disease, 37 (61.7%) were from three countries; Viet Nam (n = 20), China (n = 9) and India (n = 8).

Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2003. A report of the Australian Mycobacterium Reference Laboratory Network.

The Australian Mycobacterium Reference Laboratory Network collected and analysed laboratory data on new cases of disease caused by Mycobacterium tuberculosis complex in the year 2003. A total of 784 cases were identified by bacteriology, representing an annual reporting rate of 3.9 cases of laboratory confirmed tuberculosis per 100,000 population. The most commonly encountered culture-positive specimens were sputum (n = 351), lymph node (n = 176) and from bronchoscopy (n = 97). Smears containing acid fast bacilli were present in sputum (53.0%), bronchoscopy (32.0%) and lymph node (23.3%). Five children (female n = 3, male n = 2) under 10 years of age had bacteriologically confirmed tuberculosis. Eighty isolates of M. tuberculosis and one of Mycobacterium africanum (10.3%) were resistant to at least one of the standard anti-tuberculosis agents. Mono-resistance to isoniazid, ethambutol, rifampicin, and pyrazinamide was detected in 45, three, two, and one isolates respectively. Multidrug-resistance (MDRTB) defined as resistance to both isoniazid and rifampcin was observed in seven (0.9%) isolates. Of the seven MDRTB isolates, six were from the respiratory tract and four were from smear positive specimens. Of the 81 patients with drug resistant isolates, 78 (96.3%) were classified as having initial resistance; two had acquired resistance and no information was available for one isolate; five were Australian-born; and 76 (93.8%) had migrated from a total of 30 countries.

Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2001.

The Australian Mycobacterium Reference Laboratory Network collected and analysed laboratory data on new cases of disease caused by Mycobacterium tuberculosis complex in the year 2001. A total of 771 cases were identified, representing an annual reporting rate of 4.0 cases of laboratory-confirmed tuberculosis per 100,000 population. The predominant specimen type was sputum, (n=369) and a further 111 were collected at bronchoscopy. Smears were positive for 214 of 369 (58.0%) sputum and 42 of 111 (37.8%) bronchoscopy specimens respectively. Seven children (male n=5, female n=2) under 10 years of age had bacteriologically confirmed tuberculosis. A total of 69 isolates (8.9%), comprising 67 M. tuberculosis, one M. africanum, and one M. bovis, were resistant to at least one of the anti-tuberculosis agents. Excluding the M. bovis isolate, 61 of 64 (93.5%) were classified as having initial resistance, three had acquired resistance, and no data were available on the presence or absence of previous treatment for four patients. Resistance to at least isoniazid and/or rifampicin was noted for 67 isolates (8.7%), with resistance to both isoniazid and rifampicin (i.e. defined as multidrug-resistant disease) observed in 12 (1.6%) isolates. All of the multidrug-resistant isolates were M. tuberculosis, 10 were from the respiratory tract. The country of birth was known for 63 of 68 (92.6%) patients with a drug-resistant strain of M. tuberculosis or M. africanum; five were Australian-born and 58 (92.1%) had migrated from a total of 22 countries. One hundred and seven respiratory specimens had a nucleic acid amplification testing performed; 89 of 90 (98.9%) smear positives were nucleic acid amplification testing positive, whilst only 13 of 17 (76.5%) smear negative specimens were nucleic acid amplification testing positive. The 2001 laboratory data reveals a stable incidence rate and level of drug resistance in isolates from Australian patients with tuberculosis.

National atypical mycobacteria survey, 2000.

Infections with atypical mycobacteria in Australia during 2000 occurred at a rate of 1.8 cases per 100,000 population. The main sites of disease were the respiratory tract, soft tissue, and the lymphatics. The Mycobacterium avium complex was the most common group of mycobacteria isolated from respiratory, lymphatic sites, and blood. The rapidly growing mycobacteria, predominantly the M. fortuitum-M. abscessus-M. chelonae group were the most common soft tissue infections. Atypical mycobacteria were isolated from significant numbers of sputum 'smear positive' patients, requiring further tests to exclude M. tuberculosis. Geographical differences were observed for some Mycobacterium species, notably the isolation of M. haemophilum from Western Australia, and M. ulcerans from Victoria and Queensland. Newer molecular techniques, while improving precision and accuracy of identification, raise additional questions about the ecology of the atypical mycobacteria and their role in disease.

Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2002: a report of the Australian Mycobacterium Reference Laboratory Network.

The Australian Mycobacterium Reference Laboratory Network collected and analysed laboratory data on new cases of disease caused by Mycobacterium tuberculosis complex in the year 2002. A total of 712 cases were identified by bacteriology, representing an annual reporting rate of 3.6 cases of laboratory-confirmed tuberculosis per 100,000 population. The most commonly encountered culture-positive specimens were sputum (n=325), lymph node (n=142) and bronchoscopy (n=100). Smears containing acid fast bacilli were present in sputum (53.2%), bronchoscopy (37.9%) and lymph node (21.2%). Eight children (male n=3, female n=5) under 10 years of age had bacteriologically-confirmed tuberculosis. A total of 55 isolates (7.7%) of M. tuberculosis were resistant to at least one of the standard anti-tuberculosis agents. Resistance to at least isoniazid and/or rifampicin was noted for 53 isolates (7.4%), with multidrug-resistance (MDRTB) observed in 12 (1.9%) isolates. Of the 12 MDRTB isolates, eight were from the respiratory tract and five were from smear positive specimens. Of the patients with drug resistant M. tuberculosis isolates, 51/55 (92.7%) were classified as having initial resistance, none had acquired resistance during treatment in Australia. The country of birth was known for 54 of 55 such patients; four were Australian-born, and 50 (90.9%) had migrated from a total of 17 countries. Nucleic acid amplification testing (NAAT) was performed on 139 (19.5%) of the 712 culture-positive specimens. Of smear positive respiratory specimens, 74/80 (92.5%) were NAAT positive. For smear negative respiratory specimens, 12/17 (70.6%) reported a NAAT positive result. Importantly, false-negative NAAT results were obtained from 1/16 and 5/64 of smear positive bronchoscopy and sputum specimens respectively.