Search

As down scaling of transistors continues, there is a growing interest in developing steep-slope transistors with reduced subthreshold slope (SS) below the Boltzmann limit. In this work, we successfully fabricated steep-slope MoS2 transistors by incorporating a graphene layer, inserted in the gate stack. For our comprehensive study, we have applied density functional theory to simulate and calculate the change of SS effected by different 2D quantum materials, including graphene, germanene and 2D topological insulators, inserted within the gate dielectric. This theoretical study showed that graphene/MoS2 devices had steep SS (27.2 mV/decade), validating our experimental approach (49.2 mV/decade). Furthermore, the simulations demonstrated very steep SS (8.6 mV/decade) in WTe2/MoS2 devices. We conclude that appropriate combination of various 2D quantum materials for the gate-channel stacks, leads to steep SS and is an effective method to extend the scaling of transistors with exceptional performance.

SiGe HBTs offer significant performance advantage over Si BJTs with improved base resistance and base transit time. However, each faster technology iteration usually comes at the cost of reduced breakdown parameters. As a result, devices are often restricted to smaller operation biases, and rely on fully utilizing these imposed limits to attain maximum circuit performance. Both high voltage and high current operation have been shown to take a toll on a device’s aging behavior. One unintended consequence of technology scaling is that it forces designers to consider alternate circuit architectures and operate these devices under non-traditional modes such as reverse active, off-state, and saturation. Although not as optimal for device performance as forward active operation, these modes enable improved radiation hardening, power savings and even simpler circuit design. A bipolar transistor’s operation can be categorized into four main modes as shown in the figure below based on the applied voltage to the base-emitter (VBE) and base-collector (VCB) junctions. Due to the asymmetrical junction engineering for vertical HBTs, the forward-active mode is usually the most optimized for device performance. Because it is the most utilized mode, it is also the most characterized for device reliability. In this paper, in addition to the mixed mode stress used to characterize SiGe bipolars, we will discuss some of the recent learning in SiGe HBT reliability in the other less-understood modes of operation. We begin with a brief overview of SiGe HBT reliability physics including hot carrier generation (Auger vs. Impact-Ionization), the temperature dependence of competing mechanisms and the physical damage responsible for electrical degradation. Using measurements and simulations, we discuss in detail the device degradation under off-state and saturation modes. We demonstrate how the hot carrier generation physics responsible for degradation in the forward-active mode is still applicable in the other regions of operation. Figure 1

Discriminating similar molecules remains a very challenging problem for semiconductor gas sensors. Here, we report a method to achieve precise gas discrimination of similar chemical vapors (mesitylene, o-xylene, and toluene) by using cross-reactive arrays consisting of metal oxide semiconductor and graphene sensors. It is difficult to identify these three chemicals as they have very similar responses to these sensors. Through a cross-reactive Principal Component Analysis (PCA) of the sensor response features, however, the discrimination accuracy improved from about 70% with a single gas sensor to almost 100% with the cross-reactive sensor array. Such a precise discrimination and the low-cost planar process make this approach a very attractive candidate for smart gas sensing and for future Internet of Things (IoT) applications.

Fluorescence in situ hybridisation (FISH) was first applied on in vitro fertilisation (IVF) embryos for the preimplantation genetic diagnosis of sex, then chromosome translocations and later for chromosome copy number (PGS). Because of the controversy surrounding PGS diagnostically, it has been replaced by array-based approaches; however, FISH remains a powerful tool for investigating mechanisms of both post-zygotic segregation error and nuclear organisation, especially if most or all of the chromosomes in the karyotype can be analysed. The purpose of this study was to develop and apply a 24 chromosome FISH assay to investigate chromosome-specific rates of gain and loss, nuclear organisation patterns and the veracity of the original PGS result in days 5-6 human embryos. Analysis of 17 embryos by this newly developed approach gave strong signals for all chromosomes; it revealed chromosome copy number for each human chromosome per cell for each embryo and the nuclear address of the (mostly centromeric) loci probed. As all embryos were surplus to IVF requirements for both transfer and freezing (and many had an abnormal PGS indication) expected high levels of chromosome abnormalities were seen and no single nucleus displayed a normal complement; all were mosaic. Certain patterns emerged, however, namely that chromosome loss was more common than gain and apparent mitotic non-disjunction. Moreover, the centromeric probes tended preferentially to occupy the nuclear centre. Where we had a prior day 3 biopsy PGS result, it was confirmed, in part, by 24 colour FISH in most but not all cases.

Organisation of chromosome territories in interphase nuclei has been studied in many systems and positional alterations have been associated with disease phenotypes (e.g. laminopathies, cancer) in somatic cells. Altered nuclear organisation is also reported in developmental processes such as mammalian spermatogenesis where a "chromocentre" model is proposed with the centromeres and sex chromosomes repositioning to the nuclear centre. The purpose of this study was to test the hypothesis that alterations in nuclear organisation of human spermatozoa are associated with defects upstream in spermatogenesis (as manifest in certain infertility phenotypes). The nuclear address of (peri-) centromeric loci for 18 chromosomes (1-4, 6-12, 15-18, 20, X and Y) was assayed in 20 males using established algorithms for 3D extrapolations of 2D data. The control group comprised 10 fertile sperm donors while the test group was 10 patients with severely compromised semen parameters including high sperm aneuploidy. All loci examined in the control group adopted defined, interior positions thus providing supporting evidence for the presence of a chromocentre and interior sex chromosome territories. In the test group however there were subtle alterations in the nuclear address for certain centromeres in individual patients and, when all patient results were pooled, some different nuclear addresses were observed for chromosomes 3, 6, 12 and 18. Considering the extensive impairment of spermatogenesis in the test group (evidenced by compromised semen parameters and increased chromosome abnormalities), the observed differences in nuclear organisation for centromeric loci compared to the controls were modest. A defined pattern of nuclear reorganisation of centromeric loci in sperm heads therefore appears to be a remarkably robust process, even if spermatogenesis is severely compromised.

Background Systemic microinflammation is correlated with atherosclerosis. It needs a reliable assessment. This study explores the temporal variations of three inflammatory indexes [C-reactive protein (CRP), serum amyloid A (SAA) and interleukin-6 (IL-6)] in a period free of clinical events and tests the reliability of their multiple measurements for the assessment of microinflammation in haemodialysis (HD) patients, a population at high risk of atherosclerotic cardiovascular disease. Methods For 4 months, serum CRP, SAA and IL-6 were measured in 29 HD patients during the weeks they were free of inflammatory clinical events (> or =12 measurements for each index in every patient). The components of the variance as well as the reliability of two to five measurements for each index, aimed at assessing microinflammation precisely, were computed. Results The median (interquartile range) of CRP was 2.3 (0.9-4.9) mg/l, of SAA 3.7 (2.1-9.3) mg/l and of IL-6 4.4 (2.2-7.7) pg/ml. Patients were approximately equally distributed between three groups of low, intermediate and high variability for each index. The contribution of intraindividual (biological) variation to the total of variance was 71.3%, 69.3% and 86.7% for CRP, SAA and IL-6, respectively (higher than in all other similar studies in healthy populations). Using two measurements, the estimated reliability was 57-68% for CRP in two-thirds of the patients (comparable with that found in healthy subjects) and 57% for SAA and IL-6 in only one-third of the patients. Increasing the number of measurements up to five did not change the reliability. Conclusions Individual factors significantly influence the levels of inflammatory indexes in HD patients in periods free of inflammatory clinical events. The mean of two weekly CRP measurements, but not of SAA or IL-6, seems to assess microinflammation in most patients with a sufficient reliability.

Background: Inflammation is frequently elevated, and seems to be episodic in hemodialysis (HD) patients. Whether, its episodic character is due to the temporal variability, in periods free of clinical events, of the inflammatory indices or due, to the acute phase response induced by common inflammatory stimuli, has not been investigated yet in a longitudinal study. This study explores inflammation forms, characteristics and causes which are probably related to the high cardiovascular disease (CVD) morbidity in HD patients. Methods: In 37 HD patients, high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA) and interleukin-6 (IL-6) were weekly measured for 16 consecutive weeks. Inflammatory clinical events, in the week before every measurement, were recorded. Repeated measures ANOVA were applied for statistical analysis. Results: Fifty-one of 533 patient-weeks were positive for a clinical event. Mean ± SD (range) hs-CRP was 7.01 ± 16.06 (0.2–169) mg/l for all the weeks of the study, 38.25 ± 39.35 (2.1–169) mg/l for the weeks with clinical events and 3.70 ± 3.86 (0.2–26.1) mg/l for the weeks free of events. Variations for SAA and IL-6 were similar. ‘Clinical events’ strongly influenced acute-phase proteins and IL-6 levels. The effect of the factor ‘time’ (as assessed by inflammatory indices variation in weekly repeated measurements) was significant for all the 3 indices measured, independently of the factor ‘clinical events’. Conclusions: In periods free of clinical events, microinflammation characterizes HD patients and fluctuates in time. Inflammation due to common clinical events is added, periodically, to this microinflammation. The high level persistent microinflammation as well as the superimposed – due to clinical events – inflammation could be related to the CVD in these patients.

The widespread use of in vitro fertilization (IVF) throughout the world provides the opportunity to study human development at the very earliest stages before implantation. Nonetheless, the study of human embryos poses a series of unique ethical and moral implications. The unique totipotent nature of a human embryo and its potential to develop into a child necessitates a level of restriction and regulatory control that is not present when studying other cell types. Although some governments outlaw any experimental procedure on human embryonic material, others allow it under appropriate control. In the latter case (e.g., in the UK), experimentation can be justified on the basis of development of a diagnostic test and/or the goal of improving patient care. A further challenge to effective study is the paucity of material available. Much of the work reported in this chapter arises from the study of only single nuclei. For these reasons, research on interphase cytogenetics in human preimplantation embryos is less advanced than in other cell types. Despite this, a fundamental insight into chromosome copy number and nuclear organization can be gleaned from this material through collaboration with an appropriate clinical program. As attested by other chapters in this book, fluorescent in situ hybridization (FISH) was first adopted for research, but clinical applications rapidly followed. Prenatal and cancer diagnostics are the best examples of this,, but the increasing use of assisted reproductive technologies, namely IVF, precipitated the use of FISH in the field of preimplantation genetic diagnosis (PGD). PGD is defined as the diagnosis of genetic disorders in human preimplantation embryos. The purpose is selective implantation of unaffected embryos in the hope of establishing genetically normal ongoing pregnancies. PGD by interphase cytogenetics was first applied for sexing (to screen for sex-linked disorders), then for chromosome translocations, and later for chromosome copy number. In the latter case, termed preimplantation genetic screening (PGS), families at risk of adverse obstetrical outcomes (referral categories include advanced maternal age and recurrent miscarriage) are targeted, rather than families at risk of transmitting inherited disorders in a classical Mendelian fashion. Clinical application of interphase cytogenetics in the IVF world has allowed the subsequent study of chromosome copy number and nuclear organization. This chapter provides an overview of interphase cytogenetics in human embryos, highlighting the progress and the sometimes contentious pitfalls that it has encountered.

From the late 1980s onwards, the use of DNA probes to visualise sequences on individual chromosomes (fluorescent in-situ hybridisation - FISH) revolutionised the study of cytogenetics. Following single colour experiments, more fluorochromes were added, culminating in a 24 colour assay that could distinguish all human chromosomes. Interphase cytogenetics (the detection of chromosome copy number in interphase nuclei) soon followed, however 24 colour experiments are hampered for this application as mixing fluorochromes to produce secondary colours produces images that are not easily distinguishable from overlapping signals. This study reports the development and use of a novel protocol, new fast hybridising FISH probes, and a bespoke image capture system for the assessment of chromosome copy number in interphase nuclei. The multicolour probe sets can be used individually or in sequential hybridisation layers to assess ploidy of all 24 human chromosomes in the same nucleus. Applications of this technique are in the investigation of chromosome copy number and the assessment of nuclear organisation for a range of different cell types including human sperm, cancer cells and preimplantation embryos.

Numerous studies have implicated the role of gross genomic rearrangements in male infertility, e.g., constitutional aneuploidy, translocations, inversions, Y chromosome deletions, elevated sperm disomy, and DNA damage. The primary purpose of this paper is to review male fertility studies associated with such abnormalities. In addition, we speculate whether altered nuclear organization, another chromosomal/whole genome-associated phenomenon, is also concomitant with male factor infertility. Nuclear organization has been studied in a range of systems and implicated in several diseases. For many applications the measurement of the relative position of chromosome territories is sufficient to determine patterns of nuclear organization. Initial evidence has suggested that, unlike in the more usual ‘size-related’ or ‘gene density-related’ models, mammalian (including human) sperm heads display a highly organized pattern including a chromocenter with the centromeres located to the center of the nucleus and the telomeres near the periphery. More recent evidence, however, suggests there may be size- and gene density-related components to nuclear organization in sperm. It seems reasonable to hypothesize therefore that alterations in this pattern may be associated with male factor infertility. A small handful of studies have addressed this issue; however, to date it remains an exciting avenue for future research with possible implications for diagnosis and therapy.

Quantum dots (QDs) are a novel class of inorganic fluorochromes composed of nanometer-scale crystals made of a semiconductor material. They are resistant to photo-bleaching, have narrow excitation and emission wavelengths that can be controlled by particle size and thus have the potential for multiplexing experiments. Given the remarkable optical properties that quantum dots possess, they have been proposed as an ideal material for use in molecular cytogenetics, specifically the technique of fluorescent in situ hybridisation (FISH). In this review, we provide an account of the current QD-FISH literature, and speculate as to why QDs are not yet optimised for FISH in their current form. Prof. Darren Griffin holds the chair in genetics at the University of Kent, Canterbury, UK. He is a graduate of the University of Manchester (BSc and DSc) and University College London (PhD). He is a Fellow of the Royal College of Pathology and of the Society of Biology. He has published over 100 papers on aspects related to chromosome research and runs a busy research laboratory. Dimitris Ioannou is a final year PhD student in the laboratory of Professor Griffin. He is a graduate of the University of Wales (BSc) and Nottingham (MPhil), and has performed original research work on applications of FISH including QD-FISH.

BACKGROUND: Many genetic defects with a chromosomal basis affect male reproduction via a range of different mechanisms. Chromosome position is a well-known marker of nuclear organization, and alterations in standard patterns can lead to disease phenotypes such as cancer, laminopathies and epilepsy. It has been demonstrated that normal mammalian sperm adopt a pattern with the centromeres aligning towards the nuclear centre. The purpose of this study was to test the hypothesis that altered chromosome position in the sperm head is associated with male infertility. METHODS: The average nuclear positions of fluorescence in-situ hybridization signals for three centromeric probes (for chromosomes X, Y and 18) were compared in normoozoospermic men and in men with compromised semen parameters. RESULTS: In controls, the centromeres of chromosomes X, Y and 18 all occupied a central nuclear location. In infertile men the sex chromosomes appeared more likely to be distributed in a pattern not distinguishable from a random model. CONCLUSIONS: Our findings cast doubt on the reliability of centromeric probes for aneuploidy screening. The analysis of chromosome position in sperm heads should be further investigated for the screening of infertile men.

Studies of nuclear organisation, most commonly determining the nuclear location of chromosome territories and individual loci, have furthered our understanding of nuclear function, differentiation and disease. In this study, by examining eight loci on different chromosomes, we tested hypotheses that: (1) totipotent human blastomeres adopt a nuclear organisation akin to that of committed cells; (2) nuclear organisation is different in chromosomally abnormal blastomeres; and (3) human blastomeres adopt a `chromocentre' pattern. Analysis of in vitro fertilisation (IVF) conceptuses permits valuable insight into the cell biology of totipotent human nuclei. Here, extrapolations from images of preimplantation genetic screening (PGS) cases were used to make comparisons between totipotent blastomeres and several committed cells, showing some differences and similarities. Comparisons between chromosomally abnormal nuclei and those with no detected abnormality (NDA) suggest that the former display a significant non-random pattern for all autosomal loci, but there is a less distinct, possibly random, pattern in `NDA' nuclei. No evidence was found that the presence of an extra chromosome is accompanied by an altered nuclear location for that chromosome. Centromeric loci on chromosomes 15 and 16 normally seen at the nuclear periphery were mostly centrally located in aneuploid cells, providing some evidence of a `chromocentre'; however, the chromosome-18 centromere was more peripheral, similar to committed cells. Our results provide clues to the nature of totipotency in human cells and might have future applications for preimplantation diagnosis and nuclear transfer.

Molecular cytogenetic mapping by FISH is a common feature of most genome projects as it provides a global, low-resolution overview of the genome and facilitates comparative genomics. An essential prerequisite for cytogenetic mapping is the ability to identify accurately the chromosome on which the clone (e.g. BAC) resides. This is not usually a barrier to human mapping as knowledge of the human karyotype is commonplace. For other species however accurate assignment can be problematic either because, as in birds, the karyotype is too complex to analyze by standard means or because of the paucity of individuals skilled to perform the karyotyping. Using chicken as a model we have developed a reproducible approach for accurate cytogenetic mapping that involves: a single colour FISH, measurement of the ratio of the size of the signal bearing chromosome to that of chromosome 8, and final assignment through a small series of dual colour experiments. Reference values for size ratios were established using base pair estimate information from the Ensembl browser. By this method cytogenetic mapping to highly complex karyotypes can be achieved in a small number of simple steps. We have also developed and tested a karyotyping tutorial programme adapted from one previously reported in this journal. That is, we have used pig as an example of a model species with a relatively tractable karyotype and demonstrated that scientists and students, even after only one hour using our tutorial, can readily identify pig chromosomes and thus make appropriate assignments using FISH. Simple, practicable means often provide preferable solutions than complex alternatives (e.g. m-FISH) to the solution of scientific problems. Such is the case for the approaches described here.

Background: A reverse association between cholesterol level and cardiovascular disease mortality is observed in hemodialysis (HD) patients; this paradoxical relationship may be explained by the coexistence of inflammation. Interleukin-6 (IL-6) is a central regulator of inflammation; its action is augmented by the soluble IL-6 receptor (sIL-6R) and inhibited by the soluble gp130 (sgp130). In order to investigate the potential association of inflammation with cholesterol levels in the HD population, release of soluble IL-6 components by peripheral blood mononuclear cells (PBMCs) was measured in two groups of HD patients with distinctly different lipid profile and in a control group. Methods: Twenty-two HD patients with low serum cholesterol (range 85–171 mg/dl), 23 HD patients with high cholesterol (189–342 mg/dl) and 21 normolipidemic non-renal failure subjects were enrolled in the study. IL-6, sIL-6R and sgp130 were measured by ELISA in the serum and in the supernatant collected from cell cultures of activated or resting PBMCs isolated from all three groups. Results: Serum IL-6 and sgp130 level was higher while sIL-6R was lower in both groups of HD patients compared to the control group. The ex-vivo release of the IL-6 and sgp130 by unstimulated PBMCs did not differ significantly between the three groups but that of the sIL-6R was higher in non-renal failure than in hypercholesterolemic HD subjects. Production of sIL-6R by stimulated PBMCs was higher in low-cholesterol HD patients (p < 0.001) and the same was valid for the sgp130 release (p = 0.034). Release of IL-6 by activated PBMCs was higher in the low-cholesterol compared to the high-cholesterol HD patients group (p = 0.011 for post hoc test). Major serum lipid fractions were inversely correlated to IL-6 and sIL-6R production from stimulated PBMCs in HD but not in non-renal failure subjects. Finally, release of the sgp130 by PBMCs was significantly reduced in 13 hypertriglyceridemic – and hypercholesterolemic – HD patients. Conclusion: Production of soluble components of a crucial pro-inflammatory and potentially atherogenic cytokine, namely the IL-6, by stimulated PBMCs appears to be inversely correlated with the serum cholesterol levels in HD patients.

We have established the identity of the Schizosaccharomyces pombe homologue of vertebrate CENP-C and Saccharomyces cerevisiae MIF2p and have used it to compare Dam tagging and chromatin immunoprecipitation (ChiP)as tools for the mapping of protein binding sites on DNA. ChiP shows that S. pombe CENP-C binds to the central core and inner repeats of the S. pombe centromere. It binds weakly, however, to the outer repeats. The binding pattern is thus similar to that of S. pombe CENP-A. Dam-tagged S. pombe CENP-C, however, methylates the entire centromere and 5 kb of flanking DNA. This comparison suggests that Dam tagging is less precise as a tool for mapping DNA binding sites than ChiP. We have also used the Dam tagging technique to address the question of whether there is any CENP-C binding to the ribosomal DNA in S. pombe and find none.

Inflammation is frequently elevated, and seems to be episodic in hemodialysis (HD) patients. Whether, its episodic character is due to the temporal variability, in periods free of clinical events, of the inflammatory indices or due, to the acute phase response induced by common inflammatory stimuli, has not been investigated yet in a longitudinal study. This study explores inflammation forms, characteristics and causes which are probably related to the high cardiovascular disease (CVD) morbidity in HD patients.In 37 HD patients, high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA) and interleukin-6 (IL-6) were weekly measured for 16 consecutive weeks. Inflammatory clinical events, in the week before every measurement, were recorded. Repeated measures ANOVA were applied for statistical analysis.Fifty-one of 533 patient-weeks were positive for a clinical event. Mean +/- SD (range) hs-CRP was 7.01 +/- 16.06 (0.2-169) mg/l for all the weeks of the study, 38.25 +/- 39.35 (2.1-169) mg/l for the weeks with clinical events and 3.70 +/- 3.86 (0.2-26.1) mg/l for the weeks free of events. Variations for SAA and IL-6 were similar. 'Clinical events' strongly influenced acute-phase proteins and IL-6 levels. The effect of the factor 'time' (as assessed by inflammatory indices variation in weekly repeated measurements) was significant for all the 3 indices measured, independently of the factor 'clinical events'.In periods free of clinical events, microinflammation characterizes HD patients and fluctuates in time. Inflammation due to common clinical events is added, periodically, to this microinflammation. The high level persistent microinflammation as well as the superimposed--due to clinical events--inflammation could be related to the CVD in these patients.

not Available.

not Available.

Background The availability of the complete chicken (Gallus gallus) genome sequence as well as a large number of chicken probes for fluorescent in-situ hybridization (FISH) and microarray resources facilitate comparative genomic studies between chicken and other bird species. In a previous study, we provided a comprehensive cytogenetic map for the turkey (Meleagris gallopavo) and the first analysis of copy number variants (CNVs) in birds. Here, we extend this approach to the Pekin duck (Anas platyrhynchos), an obvious target for comparative genomic studies due to its agricultural importance and resistance to avian flu. Results We provide a detailed molecular cytogenetic map of the duck genome through FISH assignment of 155 chicken clones. We identified one inter- and six intrachromosomal rearrangements between chicken and duck macrochromosomes and demonstrated conserved synteny among all microchromosomes analysed. Array comparative genomic hybridisation revealed 32 CNVs, of which 5 overlap previously designated "hotspot" regions between chicken and turkey. Conclusion Our results suggest extensive conservation of avian genomes across 90 million years of evolution in both macro- and microchromosomes. The data on CNVs between chicken and duck extends previous analyses in chicken and turkey and supports the hypotheses that avian genomes contain fewer CNVs than mammalian genomes and that genomes of evolutionarily distant species share regions of copy number variation ("CNV hotspots"). Our results will expedite duck genomics, assist marker development and highlight areas of interest for future evolutionary and functional studies.

not Available.

In the field of nanotechnology, quantum dots (QDs) are a novel class of inorganic fluorochromes composed of nanometre-scale crystals made of a semiconductor material. Given the remarkable optical properties that they possess, they have been proposed as an ideal material for use in fluorescent in-situ hybridization (FISH). That is, they are resistant to photobleaching and they excite at a wide range of wavelengths but emit light in a very narrow band that can be controlled by particle size and thus have the potential for multiplexing experiments. The principal aim of this study was to compare the potential of QDs against traditional organic fluorochromes in both indirect (i.e. QD-conjugated streptavidin) and direct (i.e. synthesis of QD-labelled FISH probes) detection methods. In general, the indirect experiments met with a degree of success, with FISH applications demonstrated for chromosome painting, BAC mapping and use of oligonucleotide probes on human and avian chromosomes/nuclei. Many of the reported properties of QDs (e.g. brightness, 'blinking' and resistance to photobleaching) were observed. On the other hand, signals were more frequently observed where the chromatin was less condensed (e.g. around the periphery of the chromosome or in the interphase nucleus) and significant bleed-through to other filters was apparent (despite the reported narrow emission spectra). Most importantly, experimental success was intermittent (sometimes even in identical, parallel experiments) making attempts to improve reliability difficult. Experimentation with direct labelling showed evidence of the generation of QD-DNA constructs but no successful FISH experiments. We conclude that QDs are not, in their current form, suitable materials for FISH because of the lack of reproducibility of the experiments; we speculate why this might be the case and look forward to the possibility of nanotechnology forming the basis of future molecular cytogenetic applications.