STEM electron beam-induced current measurements of organic-inorganic perovskite solar cells.

We describe a new approach for preparing organic-inorganic perovskite solar cells for electron beam-induced current (EBIC) measurements in plan-view geometry. This method substantially reduces sample preparation artefacts, provides good electrical contact and keeps the preparation steps as close as possible to those for real devices. Our EBIC images were acquired simultaneously with annular dark-field scanning transmission electron microscopy images using a home-made highly sensitive EBIC amplifier. High-angle annular dark-field images and energy dispersive X-ray maps were recorded from the same area immediately afterwards. This allowed the EBIC contrast to be correlated with regions containing N and a deficiency of O. The EBIC contrast was also found to be similar to secondary electron contrast recorded with a scanning electron microscope. By identifying the generation and absorption electron processes, we determine that EBIC cannot be separated from the secondary electron and absorbed currents. This means that careful analysis needs to be performed before conclusions can be made on the origin of the current measured across p-n or p-i-n junctions.

Collective electronic excitations in the ultra violet regime in 2-D and 1-D carbon nanostructures achieved by the addition of foreign atoms.

Plasmons in the visible/UV energy regime have attracted great attention, especially in nano-materials, with regards to applications in opto-electronics and light harvesting; tailored enhancement of such plasmons is of particular interest for prospects in nano-plasmonics. This work demonstrates that it is possible, by adequate doping, to create excitations in the visible/UV regime in nano-carbon materials, i.e., carbon nanotubes and graphene, with choice of suitable ad-atoms and dopants, which are introduced directly into the lattice by low energy ion implantation or added via deposition by evaporation. Investigations as to whether these excitations are of collective nature, i.e., have plasmonic character, are carried out via DFT calculations and experiment-based extraction of the dielectric function. They give evidence of collective excitation behaviour for a number of the introduced impurity species, including K, Ag, B, N, and Pd. It is furthermore demonstrated that such excitations can be concentrated at nano-features, e.g., along nano-holes in graphene through metal atoms adhering to the edges of these holes.

Three-wave electron vortex lattices for measuring nanofields.

It is demonstrated how an electron-optical arrangement consisting of two electron biprisms can be used to generate three-wave vortex lattices with effective lattice spacings between 0.1 and 1 nm. The presence of vortices in these lattices was verified by using a third biprism to perform direct phase measurements via off-axis electron holography. The use of three-wave lattices for nanoscale electromagnetic field measurements via vortex interferometry is discussed, including the accuracy of vortex position measurements and the interpretation of three-wave vortex lattices in the presence of partial spatial coherence.

Hybridization approach to in-line and off-axis (electron) holography for superior resolution and phase sensitivity.

Holography--originally developed for correcting spherical aberration in transmission electron microscopes--is now used in a wide range of disciplines that involve the propagation of waves, including light optics, electron microscopy, acoustics and seismology. In electron microscopy, the two primary modes of holography are Gabor's original in-line setup and an off-axis approach that was developed subsequently. These two techniques are highly complementary, offering superior phase sensitivity at high and low spatial resolution, respectively. All previous investigations have focused on improving each method individually. Here, we show how the two approaches can be combined in a synergetic fashion to provide phase information with excellent sensitivity across all spatial frequencies, low noise and an efficient use of electron dose. The principle is also expected to be widely to applications of holography in light optics, X-ray optics, acoustics, ultra-sound, terahertz imaging, etc.

Atomic resolution imaging and spectroscopy of barium atoms and functional groups on graphene oxide.

We present an atomic resolution transmission electron microscopy (TEM) and scanning TEM (STEM) study of the local structure and composition of graphene oxide modified with Ba(2+). In our experiments, which are carried out at 80kV, the acquisition of contamination-free high-resolution STEM images is only possible while heating the sample above 400°C using a highly stable heating holder. Ba atoms are identified spectroscopically in electron energy-loss spectrum images taken at 800°C and are associated with bright contrast in high-angle annular dark-field STEM images. The spectrum images also show that Ca and O occur together and that Ba is not associated with a significant concentration of O. The electron dose used for spectrum imaging results in beam damage to the specimen, even at elevated temperature. It is also possible to identify Ba atoms in high-resolution TEM images acquired using shorter exposure times at room temperature, thereby allowing the structure of graphene oxide to be studied using complementary TEM and STEM techniques over a wide range of temperatures.

Ion implantation of graphene-toward IC compatible technologies.

Doping of graphene via low energy ion implantation could open possibilities for fabrication of nanometer-scale patterned graphene-based devices as well as for graphene functionalization compatible with large-scale integrated semiconductor technology. Using advanced electron microscopy/spectroscopy methods, we show for the first time directly that graphene can be doped with B and N via ion implantation and that the retention is in good agreement with predictions from calculation-based literature values. Atomic resolution high-angle dark field imaging (HAADF) combined with single-atom electron energy loss (EEL) spectroscopy reveals that for sufficiently low implantation energies ions are predominantly substitutionally incorporated into the graphene lattice with a very small fraction residing in defect-related sites.

Comparison of approaches and artefacts in the measurement of detector modulation transfer functions.

In order to investigate the reproducibility of measurements of transmission electron microscope detector modulation transfer functions (MTFs) we measure the MTF of a charge-coupled device (CCD) camera using five different methods. MTFs derived from a sharp edge, a circular aperture and electron holographic interference fringes are found to agree closely with one other. The difficulty of obtaining accurate measurements of MTFs and the potential of using focused electron probes to make direct measurements of MTFs is discussed. We highlight the sensitivity of image contrast after deconvolution to small differences in the measured MTF.

A randomized controlled trial of fallopian tube sperm perfusion compared with standard intrauterine insemination for women with non-tubal infertility.

STUDY QUESTION: Does fallopian tube sperm perfusion (FSP) result in better pregnancy and live birth rates than standard intrauterine insemination (SIUI) for couples with non-tubal infertility with or without gonadotrophin or clomiphene stimulation? SUMMARY ANSWER: There was no evidence of an improvement in live birth rates with FSP compared with SIUI. WHAT IS KNOWN ALREADY: Previous randomized controlled trials have suggested improved live birth rates with FSP but these trials were small. A systematic review published in 2004 suggested heterogeneity in results. STUDY DESIGN, SIZE, AND DURATION: This pragmatic, multicentre, randomized controlled trial compared SIUI and FSP in 417 women with non-tubal infertility. PARTICIPANTS/MATERIALS, SETTING, METHODS: The patients were treated at fertility clinics in New Zealand, Australia and the United Arab Emirates. MAIN RESULTS AND THE ROLE OF CHANCE: Four hundred and seventeen women were randomized to SIUI (n = 210) or FSP (n = 207). Data were available for analysis from 198 women in the SIUI group and 198 women in the FSP group. There were 19 women with incomplete data because of cycle cancellation or withdrawals and 2 women who conceived prior to commencing treatment. There were no significant differences in live birth rates between the two groups with 27 (12.9%) in the SIUI group and 21 in the FSP group (10.1%) [Odds Ratio (OR) 1.31 (0.71, 2.39), P = 0.48]. Two ectopic pregnancies were reported in the SIUI group and one was reported in the FSP group. LIMITATIONS, REASONS FOR CAUTION: Different ovulation protocols were used in the different clinics. Approximately 10% of the cycles involved donor sperm and ∼5% of the cycles did not complete the assigned intervention. WIDER IMPLICATIONS OF THE FINDINGS: There was no evidence of an improvement in live birth rates with FSP compared with SIUI. STUDY FUNDING/COMPETING INTEREST(S): The study was funded in part by the A+ trust of the Auckland District Health Board. No commercial funding was received. TRIAL REGISTRATION NUMBER: ANZCTR Number ACTRN12612001303831.

Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation.

BACKGROUND: Infertility due to anovulation is a common problem in women. The first line oral treatment is with anti-oestrogens, such as clomiphene citrate. Unfortunately there may be resistance and alternative and adjunctive treatments have been developed. These include tamoxifen, dexamethasone, bromocriptine and aromatase inhibitors (AIs). OBJECTIVES: To determine the relative effectiveness of anti-oestrogen agents, with or without medical adjuncts, in women with WHO group 2 anovulation. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trial register (searched 5th July 2004), CENTRAL (The Cochrane Library Issue 2 2004), MEDLINE (1966 to June 2004) and EMBASE (1980 to June 2004) for identification of relevant randomised controlled trials (RCTs). Additionally the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs were searched. SELECTION CRITERIA: RCTs that compare oral anti-oestrogen agents for ovulation induction (alone or in conjunction with medical adjuncts) in anovulatory subfertility, were considered for inclusion in the review. Metformin and other insulin sensitizing agents were not included. Hyperprolactinaemic infertility was not included. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment was done independently by two reviewers. The primary outcome was live birth, secondary outcomes were: pregnancy, ovulation, miscarriage, multiple pregnancy, overstimulation, ovarian hyperstimulation syndrome and patient reported adverse effects. MAIN RESULTS: Twelve RCTs were found and included in this review. No trials reported live birth as an outcome. Miscarriage and multiple pregnancy rates were poorly reported. Clomiphene was shown to be effective in increasing pregnancy rate when compared to placebo (fixed OR 5.8, 95% CI 1.6 to 21.5; NNT 5.9, 95% CI 3.6 to 16.7). No evidence of a difference in effect was found between clomiphene and tamoxifen (fixed OR 1.0, 95% CI 0.5 to 2.1). The use of clomiphene in combination with tamoxifen did not find any evidence of effect on pregnancy rate when compared to clomiphene alone (fixed OR 3.3, 95% CI 0.1 to 91.6). The comparison between two AIs (letrozole and anastrozole) did not find any evidence of a difference in effect on pregnancy rate (fixed OR 1.9, 95% CI 0.4 to 8.9). For the intervention of clomiphene plus ketoconazole vs clomiphene no evidence of a difference in effect for pregnancy rate was found (fixed OR 2.4, 95% CI 0.9 to 6.4). For clomiphene plus bromocriptine vs clomiphene no evidence of a difference in effect on pregnancy rate was found (fixed OR 1.0, 95% CI 0.3 to 3.0) rates. However, clomiphene plus dexamethasone treatment resulted in a significant improvement in the pregnancy rate (fixed OR 11.3, 95% CI 5.3 to 24.0; NNT 2.7, 95% CI 2.1 to 3.6) when compared to clomiphene alone as did clomiphene plus pretreatment with combined oral contraceptives (fixed OR 27.2, 95% CI 3.1 to 235.0; NNT 2.0, 95% CI 1.4 to 3.4). AUTHORS' CONCLUSIONS: This review shows evidence supporting the effectiveness of the current first line treatment, clomiphene citrate. No evidence of a difference in effect was found between clomiphene and tamoxifen. The use of dexamethasone as an adjunct to clomiphene therapy appears promising as do combined oral contraceptives. This review has highlighted a gap in the literature on effects of these drugs on outcomes such as miscarriage rate. Evidence in favour of these interventions is flawed. RCTs of adequate power and of high methodological quality are required for the older treatments such as clomiphene, alone and with medical adjuncts, and also for the newer drugs such as the AIs.

The contribution of phonon scattering to high-resolution images measured by off-axis electron holography.

The contribution of electrons that have been phonon scattered to the lattice fringe amplitude and the background intensity of a high-resolution electron microscope (HREM) image is addressed experimentally through the analysis of a defocus series of energy-filtered off-axis electron holograms. It is shown that at a typical specimen thickness used for HREM imaging approximately 15% of the electrons that contribute to an energy-filtered image have been phonon scattered. At this specimen thickness, the phonon-scattered electrons contribute a lattice image of opposite contrast to the elastic lattice image. The overall lattice fringe contrast is then reduced to 70% of the value that it would have in the absence of phonon scattering. At higher specimen thickness, the behaviour is defocus-dependent, with the phonon image having lattice fringe contrast of either the same or the opposite sense to the elastic image as the defocus is varied.

The phonon contribution to high-resolution electron microscope images.

The amount of phonon scattering as a function of specimen thickness is determined for a clean silicon sample, free from amorphous surface layers, by measuring the diffuse scattering in energy-filtered convergent-beam diffraction patterns. It is found that for a 25 nm thick sample, only 7.5% of the intensity scattered to less than 18 nm(-1) is phonon scattered. This means that in a typical high-resolution sample most of the diffuse scattering is caused by surface amorphous layers rather than phonon scattering.

Circadian regulation of gene expression systems in the Drosophila head.

Mechanisms composing Drosophila's clock are conserved within the animal kingdom. To learn how such clocks influence behavioral and physiological rhythms, we determined the complement of circadian transcripts in adult Drosophila heads. High-density oligonucleotide arrays were used to collect data in the form of three 12-point time course experiments spanning a total of 6 days. Analyses of 24 hr Fourier components of the expression patterns revealed significant oscillations for approximately 400 transcripts. Based on secondary filters and experimental verifications, a subset of 158 genes showed particularly robust cycling and many oscillatory phases. Circadian expression was associated with genes involved in diverse biological processes, including learning and memory/synapse function, vision, olfaction, locomotion, detoxification, and areas of metabolism. Data collected from three different clock mutants (per(0), tim(01), and Clk(Jrk)), are consistent with both known and novel regulatory mechanisms controlling circadian transcription.

Long-term time estimation is influenced by circadian phase.

The adaptive significance of a putative time sense in humans remains unclear as do the factors that underlie the capacity to gauge the passage of time. Here we show that the subjective assessment of relatively long durations varies systematically as a function of time of day. Specifically, the subjective clock ran relatively faster when the circadian oscillation of body temperature was on the rise and relatively slower on the declining portion of the temperature curve. The overall result was a rather labile clock that, on average, ran slow relative to physical time. The results provide a glimpse into an underexplored aspect of how humans use their endogenous clocks in the most fundamental way--to gauge the passage of time.

Tungsten disulphide sheathed carbon nanotubes.

An insulated nanotube wire is formed by the binary phase of layered tungsten disulphide and carbon nanotubes (shown in the HRTEM image) generated by the sulphidization of tungsten oxide coated multiwalled carbon nanotubes at 900 °C. Thermogravimetric analysis shows that the tungsten disulphide coat acts as an antioxidant.

Identification of somatic mutations of the MEN1 gene in sporadic endocrine tumours.

Endocrine tumours of the pancreas, anterior pituitary or parathyroids arise either sporadically in the general population, or as a part of inherited syndromes such as multiple endocrine neoplasia type 1 (MEN 1). The mechanisms responsible for the development of sporadic endocrine lesions are not well understood, although loss of heterozygosity (LOH) of the MEN1 locus on chromosome 11q13 and somatic mutation of the MEN1 gene have been frequently associated with the development of MEN 1-type sporadic endocrine lesions. To further investigate the role of the MEN1 gene in sporadic endocrine tumorigenesis, we analysed DNA from 14 primary parathyroid lesions, 8 anterior pituitary tumours and 3 pancreatic tumours for the presence of somatic MEN1 gene mutations and LOH of seven microsatellite markers flanking the MEN1 locus. In addition, we similarly analysed 8 secondary parathyroid lesions which arose in patients with chronic renal failure. None of the patients studied had a family history of MEN 1. Three primary parathyroid lesions and one pancreatic tumour (glucagonoma) were found to have lost one allele at the MEN1 locus. Somatic mutations were identified by SSCP and sequence analysis in one of these parathyroid lesions (P320L) and in the glucagonoma (E179V). These results support previous findings that inactivation of the MEN1 tumour suppressor gene contributes to the development of sporadic MEN 1-type endocrine lesions but is not associated with the development of parathyroid hyperplasia seen in some renal failure patients.

G protein mutations in tumours of the pituitary, parathyroid and endocrine pancreas.

A subset of growth-hormone (GH) producing pituitary adenomas harbour mutations at residues Arg201 and Gln227 of the alpha subunit of the stimulatory G protein (Gs alpha). One such mutation has been reported in a GH-producing tumour from a patient with multiple endocrine neoplasia type 1 (MEN 1) although mutations have not been reported in other tumours associated with MEN 1. We used PCR-induced restriction site analysis to screen for these mutations in 80 tumours of the pituitary, parathyroid and endocrine pancreas. Arg201 mutations were detected in 1 non-functioning and 4 GH-producing pituitary tumours. No mutations were found in any of the endocrine tumours tested at Arg179 of the Gi2 alpha subunit, a homologous residue to Arg201 of Gs alpha. Our results indicate oncogenesis in the majority of pituitary and parathyroid tumours is independent of mutations of Gs and Gi2 alpha.

Single base mutation in the hormone binding domain of the thyroid hormone receptor beta gene in generalised thyroid hormone resistance demonstrated by single stranded conformation polymorphism analysis.

Thyroid hormone resistance is a syndrome of considerable clinical heterogeneity. Three mutations in the c-erb A beta gene encoding the human beta thyroid hormone receptor have been described in different kindreds. We report here, in a family affected with peripheral thyroid hormone resistance, a unique point mutation in the ligand binding domain of the c-erb A beta gene resulting in histidine replacement of an arginine residue at position 438. The region in which the mutation occurred was identified by single stranded conformation polymorphism analysis and confirmed by subcloning and sequencing of the mutant alleles from each of the affected members. Binding of tri-iodothyronine to isolated nuclei from family members was normal suggesting the mechanism of thyroid hormone resistance in this family is not mediated by abnormal binding of ligand and receptor.

Genetic studies on the beta subunit of Escherichia coli RNA polymerase. III. Analysis of low-level rifampicin-resistant mutants.

Spontaneously-occurring rifampicin-resistant mutants that survive on low (20 micrograms ml-1) but not high drug concentrations (200 micrograms ml-1) have been isolated. One such mutation appears to map close to residue 650 on the beta structural gene. RNA polymerase from low-level resistant strains shows an intermediate response to rifampicin in vitro: both the association and dissociation rates of the antibiotic are markedly reduced. Continued expression of this unusual phenotype upon introduction of a high-level resistance allele is described in terms of DNA blockade.