Generation of uniform plasmas by crossed internal oscillating current sheets : key concepts and experimental verification

The results of comprehensive experimental studies of the operation, stability, and plasma parameters of the low-frequency (0.46 MHz) inductively coupled plasmas sustained by the internal oscillating rf current are reported. The rf plasma is generated by using a custom-designed configuration of the internal rf coil that comprises two perpendicular sets of eight currents in each direction. Various diagnostic tools, such as magnetic probes, optical emission spectroscopy, and an rf-compensated Langmuir probe were used to investigate the electromagnetic, optical, and global properties of the argon plasma in wide ranges of the applied rf power and gas feedstock pressure. It is found that the uniformity of the electromagnetic field inside the plasma reactor is improved as compared to the conventional sources of inductively coupled plasmas with the external flat coil configuration. A reasonable agreement between the experimental data and computed electromagnetic field topography inside the chamber is reported. The Langmuir probe measurements reveal that the spatial profiles of the electron density, the effective electron temperature, plasma potential, and electron energy distribution/probability functions feature a high degree of the radial and axial uniformity and a weak azimuthal dependence, which is consistent with the earlier theoretical predictions. As the input rf power increases, the azimuthal dependence of the global plasma parameters vanishes. The obtained results demonstrate that by introducing the internal oscillated rf currents one can noticeably improve the uniformity of electromagnetic field topography, rf power deposition, and the plasma density in the reactor.

Inductively coupled plasmas sustained by an internal oscillating current

A global electromagnetic model of an inductively coupled plasma sustained by an internal oscillating current sheet in a cylindrical metal vessel is developed. The electromagnetic field structure, profiles of the rf power transferred to the plasma electrons, electron/ion number density, and working points of the discharge are studied, by invoking particle and power balance. It is revealed that the internal rf current with spatially invariable phase significantly improves the radial uniformity of the electromagnetic fields and the power density in the chamber as compared with conventional plasma sources with external flat spiral inductive coils. This configuration offers the possibility of controlling the rf power deposition in the azimuthal direction.

Human single-stranded DNA binding protein 1 (hSSB1/NABP2) is required for the stability and repair of stalled replication forks

Aberrant DNA replication is a primary cause of mutations that are associated with pathological disorders including cancer. During DNA metabolism, the primary causes of replication fork stalling include secondary DNA structures, highly transcribed regions and damaged DNA. The restart of stalled replication forks is critical for the timely progression of the cell cycle and ultimately for the maintenance of genomic stability. Our previous work has implicated the single-stranded DNA binding protein, hSSB1/NABP2, in the repair of DNA double-strand breaks via homologous recombination. Here, we demonstrate that hSSB1 relocates to hydroxyurea (HU)-damaged replication forks where it is required for ATR and Chk1 activation and recruitment of Mre11 and Rad51. Consequently, hSSB1-depleted cells fail to repair and restart stalled replication forks. hSSB1 deficiency causes accumulation of DNA strand breaks and results in chromosome aberrations observed in mitosis, ultimately resulting in hSSB1 being required for survival to HU and camptothecin. Overall, our findings demonstrate the importance of hSSB1 in maintaining and repairing DNA replication forks and for overall genomic stability.

Development of reverse phase protein microarrays for clinical applications and patient-tailored therapy

While genomics provide important information about the somatic genetic changes, and RNA transcript profiling can reveal important expression changes that correlate with outcome and response to therapy, it is the proteins that do the work in the cell. At a functional level, derangements within the proteome, driven by post-translational and epigenetic modifications, such as phosphorylation, is the cause of a vast majority of human diseases. Cancer, for instance, is a manifestation of deranged cellular protein molecular networks and cell signaling pathways that are based on genetic changes at the DNA level. Importantly, the protein pathways contain the drug targets in signaling networks that govern overall cellular survival, proliferation, invasion and cell death. Consequently, the promise of proteomics resides in the ability to extend analysis beyond correlation to causality. A critical gap in the information knowledge base of molecular profiling is an understanding of the ongoing activity of protein signaling in human tissue: what is activated and “in use” within the human body at any given point in time. To address this gap, we have invented a new technology, called reverse phase protein microarrays, that can generate a functional read-out of cell signaling networks or pathways for an individual patient obtained directly from a biopsy specimen. This “wiring diagram” can serve as the basis for both, selection of a therapy and patient stratification.

Effect of an internal rotating current on low-frequency inductively coupled plasmas

The effects of an inductively rotating current were observed on low-frequency inductively coupled plasmas. The spatial distribution of electromagnetic fields was investigated in a cylindrical metallic chamber filled with dense plasma. The distribution of the magnetic field in plasma chamber was observed for rarefied and dense plasmas. The plasma was assumed as uniform in the electromagnetic fields. The results showed the plasma density increased with power and the electron density increased with pressure.

Internal oscillating current-sustained RF plasmas : Parameters, stability, and potential for surface engineering

A new source of low-frequency (0.46 MHz) inductively coupled plasmas sustained by the internal planar "unidirectional" RF current driven through a specially designed internal antenna configuration has been developed. The experimental results of the investigation of the optical and global argon plasma parameters by the optical and Langmuir probes are presented. It is shown that the spatial profiles of the electron density, the effective electron temperature and plasma potential feature a great deal of the radial and axial uniformity compared with conventional sources of inductively coupled plasmas with external at coil configurations. The measurements also reveal a weak azimuthal dependence of the global plasma parameters at low values of the input RF power, which was earlier predicted theoretically. The azimuthal dependence of the global plasma parameters vanishes at high input RF powers. Moreover, under certain conditions, the plasma becomes unstable due to spontaneous transitions between low-density (electrostatic, E) and high-density (electromagnetic, H) operating modes. Excellent uniformity of high-density plasmas makes the plasma reactor promising for various plasma processing applications and surface engineering.

Discharge mode transitions in low-frequency inductively coupled plasmas with internal oscillating current sheets

Transitions between the two discharge modes in a low-frequency (∼460 kHz) inductively coupled plasma sustained by an internal oscillating radio frequency (rf) current sheet are studied. The unidirectional rf current sheet is generated by an internal antenna comprising two orthogonal sets of synphased rf currents driven in alternately reconnected copper litz wires. It is shown that in the low-to-intermediate pressure range the plasma source can be operated in the electrostatic (E) and electromagnetic (H) discharge modes. The brightness of the E -mode argon plasma glow is found remarkably higher than in inductively coupled plasmas with external flat spiral "pancake" coils. The cyclic variations of the input rf power result in pronounced hysteretic variations of the optical emission intensity and main circuit parameters of the plasma source. Under certain conditions, it appears possible to achieve a spontaneous E→H transition ("self-transition"). The observed phenomenon can be attributed to the thermal drift of the plasma parameters due to the overheating of the working gas. The discharge destabilizing factors due to the gas heating and step-wise ionization are also discussed. © 2005 American Vacuum Society.

Magnetic fields and uniformity of radio frequency power deposition in low-frequency inductively coupled plasmas with crossed internal oscillating currents

Radial and axial distributions of magnetic fields in a low-frequency (∼460 kHz)inductively coupled plasmasource with two internal crossed planar rf current sheets are reported. The internal antenna configuration comprises two orthogonal sets of eight alternately reconnected parallel and equidistant copper litz wires in quartz enclosures and generates three magnetic (H z, H r, and H φ) and two electric (E φ and E r) field components at the fundamental frequency. The measurements have been performed in rarefied and dense plasmas generated in the electrostatic(E) and electromagnetic (H)discharge modes using two miniature magnetic probes. It is shown that the radial uniformity and depth of the rf power deposition can be improved as compared with conventional sources of inductively coupled plasmas with external flat spiral (“pancake”) antennas. Relatively deeper rf power deposition in the plasma source results in more uniform profiles of the optical emission intensity, which indicates on the improvement of the plasma uniformity over large chamber volumes. The results of the numerical modeling of the radial magnetic field profiles are found in a reasonable agreement with the experimental data.

Standards that we can 'own' : Threshold Learning Outcomes for Journalism, Public Relations, and Media & Communication Studies

This paper outlines the progress by the JoMeC (Journalism, Media & Communication) Network in developing TLO (Threshold Learning Outcome) statements for Bachelor-level university programs in the disciplines of Journalism, Public Relations and Media & Communications Studies. The paper presents the finalised TLO statement for Journalism, and outlines moves to engage discipline-based groups to further develop preliminary TLOs for Public Relations and Media & Communication Studies. The JoMeC Network was formed in 2011, in response to requirements that from 2014 all degrees and qualifications at Australian universities would be able to demonstrate that they comply with the threshold learning standards set by the Australian Qualifications Framework (AQF). The AQF’s threshold standards define the minimum types and levels of knowledge, skills and capabilities that a student must demonstrate in order to graduate. The Tertiary Education Quality and Standards Agency (TEQSA) will use the AQF’s threshold standards as a key tool in recording and assessing the performance of higher educational institutions, and determining whether they should be registered as Australian Higher Education Providers under the Higher Education Standards Framework. The Office of Learning & Teaching (OLT) places the onus on discipline communities to collaborate in order to develop and ‘own’ the threshold learning standards that can be considered the minimum learning outcomes of university-level programs in that field. With the support of an OLT Grant, the JoMeC Network’s prime goal has been to develop three sets of discipline-specific TLOs – one each for the Journalism, Public Relations, and Media & Communications Studies disciplines. This paper describes the processes of research, consultation, drafting and ongoing revision of the TLO for Journalism. It outlines the processes that the JoMeC Network has taken in developing a preliminary TLO draft to initiate discussion of Public Relations and Media & Communication Studies. The JoMeC Network plans to hand management of further development of these TLOs to scholars within the discipline who will engage with academics and other stakeholders to develop statements that the respective disciplines can embrace and ‘own’.

Drosophila 3′ UTRs are more complex than protein-coding sequences

The 3′ UTRs of eukaryotic genes participate in a variety of post-transcriptional (and some transcriptional) regulatory interactions. Some of these interactions are well characterised, but an undetermined number remain to be discovered. While some regulatory sequences in 3′ UTRs may be conserved over long evolutionary time scales, others may have only ephemeral functional significance as regulatory profiles respond to changing selective pressures. Here we propose a sensitive segmentation methodology for investigating patterns of composition and conservation in 3′ UTRs based on comparison of closely related species. We describe encodings of pairwise and three-way alignments integrating information about conservation, GC content and transition/transversion ratios and apply the method to three closely related Drosophila species: D. melanogaster, D. simulans and D. yakuba. Incorporating multiple data types greatly increased the number of segment classes identified compared to similar methods based on conservation or GC content alone. We propose that the number of segments and number of types of segment identified by the method can be used as proxies for functional complexity. Our main finding is that the number of segments and segment classes identified in 3′ UTRs is greater than in the same length of protein-coding sequence, suggesting greater functional complexity in 3′ UTRs. There is thus a need for sustained and extensive efforts by bioinformaticians to delineate functional elements in this important genomic fraction. C code, data and results are available upon request.

Modeling of protein signaling networks in clinical proteomics

Molecular interactions that underlie pathophysiological states are being elucidated using techniques that profile proteomicend points in cellular systems. Within the field of cancer research, protein interaction networks play pivotal roles in the establishment and maintenance of the hallmarks of malignancy, including cell division, invasion, and migration. Multiple complementary tools enable a multifaceted view of how signal protein pathway alterations contribute to pathophysiological states.One pivotal technique is signal pathway profiling of patient tissue specimens. This microanalysis technology provides a proteomic snapshot at one point in time of cells directly procured from the native context of a tumor micro environment. To study the adaptive patterns of signal pathway events over time, before and after experimental therapy, it is necessary to obtain biopsies from patients before, during, and after therapy. A complementary approach is the profiling of cultured cell lines with and without treatment. Cultured cell models provide the opportunity to study short-term signal changes occurring over minutes to hours. Through this type of system, the effects of particular pharmacological agents may be used to test the effects of signal pathway inhibition or activation on multiple endpoints within a pathway. The complexity of the data generated has necessitated the development of mathematical models for optimal interpretation of interrelated signaling pathways. In combination,clinical proteomic biopsy profiling, tissue culture proteomic profiling, and mathematical modeling synergistically enable a deeper understanding of how protein associations lead to disease states and present new insights into the design of therapeutic regimens.

Changes in teachers’ behaviour in secondary science education : implementing a standards-referenced national curriculum

There is substantial attention worldwide to the quality of secondary school teaching in STEM in Education. This paper reports on the use of Outcome Mapping (OM) as an approach to guide and monitor change in teacher practice and a visual tool, shaped as a Star, to benchmark and monitor this behaviour. OM and the visual tool were employed to guide and document three secondary teachers’ behaviour as they planned, implemented and assessed a science unit in the new Australian standards-referenced curriculum. Five key outcome markers in the teachers’ behaviour were identified together with progress markers — cumulative qualitative indicators — leading to these outcomes. The use of a Star to benchmark and track teachers’ behaviours was particularly useful because it showed teacher behaviour on multiple dimensions simultaneously at various points in time. It also highlighted priorities in need of further attention and provided a pathway to achievement. Hence, OM and the Star representation provide both theoretical and pragmatic approaches to enhancing quality in STEM teaching.

Plasmodium falciparum parasites lacking histidine-rich protein 2 and 3 : a review and recommendations for accurate reporting

Malaria rapid diagnostic tests (RDTs) play a critical role in malaria case management, surveillance and case investigations. Test performance is largely determined by design and quality characteristics, such as detection sensitivity, specificity, and thermal stability. However, parasite characteristics such as variable or absent expression of antigens targeted by RDTs can also affect RDT performance. Plasmodium falciparum parasites lacking the PfHRP2 protein, the most common target antigen for detection of P. falciparum, have been reported in some regions. Therefore, accurately mapping the presence and prevalence of P. falciparum parasites lacking pfhrp2 would be an important step so that RDTs targeting alternative antigens, or microscopy, can be preferentially selected for use in such regions. Herein the available evidence and molecular basis for identifying malaria parasites lacking PfHRP2 is reviewed, and a set of recommended procedures to apply for future investigations for parasites lacking PfHRP2, is proposed.

The Saccharomyces cerevisiae RNA-binding protein Rbp29 functions in cytoplasmic mRNA metabolism

Here we report that the Saccharomyces cerevisiae RBP29 (SGN1, YIR001C) gene encodes a 29-kDa cytoplasmic protein that binds to mRNA in vivo. Rbp29p can be co-immunoprecipitated with the poly(A) tail-binding protein Pab1p from crude yeast extracts in a dosageand RNA-dependent manner. In addition, recombinant Rbp29p binds preferentially to poly(A) with nanomolar binding affinity in vitro. Although RBP29 is not essential for cell viability, its deletion exacerbates the slow growth phenotype of yeast strains harboring mutations in the eIF4G genes TIF4631 and TIF4632. Furthermore, overexpression of RBP29 suppresses the temperaturesensitive growth phenotype of specific tif4631, tif4632, and pab1 alleles. These data suggest that Rbp29p is an mRNA-binding protein that plays a role in modulating the expression of cytoplasmic mRNA.

Modelling the dynamics of Plasmodium falciparum histidine-rich protein 2 in human malaria to better understand malaria rapid diagnostic test performance

BACKGROUND: Effective diagnosis of malaria is a major component of case management. Rapid diagnostic tests (RDTs) based on Plasmodium falciparumhistidine-rich protein 2 (PfHRP2) are popular for diagnosis of this most virulent malaria infection. However, concerns have been raised about the longevity of the PfHRP2 antigenaemia following curative treatment in endemic regions. METHODS: A model of PfHRP2 production and decay was developed to mimic the kinetics of PfHRP2 antigenaemia during infections. Data from two human infection studies was used to fit the model, and to investigate PfHRP2 kinetics. Four malaria RDTs were assessed in the laboratory to determine the minimum detectable concentration of PfHRP2. RESULTS: Fitting of the PfHRP2 dynamics model indicated that in malaria naive hosts, P. falciparum parasites of the 3D7 strain produce 1.4 x 10(-)(1)(3) g of PfHRP2 per parasite per replication cycle. The four RDTs had minimum detection thresholds between 6.9 and 27.8 ng/mL. Combining these detection thresholds with the kinetics of PfHRP2, it is predicted that as few as 8 parasites/muL may be required to maintain a positive RDT in a chronic infection. CONCLUSIONS: The results of the model indicate that good quality PfHRP2-based RDTs should be able to detect parasites on the first day of symptoms, and that the persistence of the antigen will cause the tests to remain positive for at least seven days after treatment. The duration of a positive test result following curative treatment is dependent on the duration and density of parasitaemia prior to treatment and the presence and affinity of anti-PfHRP2 antibodies.