MicroRNAs targeting mutant K-ras by electrotransfer inhibit human colorectal adenocarcinoma cell growth in vitro and in vivo

Mutations of K-ras have been found in 30-60% of colorectal carcinomas and are believed to be associated with tumor initiation, tumor progression and metastasis formation. Therefore, silencing of mutant K-ras expression has become an attractive therapeutic strategy for colorectal cancer treatment. The aim of our study was to investigate the effect of microRNA (miRNA) molecules directed against K-ras (miRNA-K-ras) on K-ras expression level and the growth of colorectal carcinoma cell line LoVo in vitro and in vivo. In addition, we evaluated electroporation as a gene delivery method for transfection of LoVo cells and tumors with plasmid DNA encoding miRNA-K-ras (pmiRNA-K-ras). Results of our study indicated that miRNAs targeting K-ras efficiently reduced K-ras expression and cell survival after in vitro electrotransfection of LoVo cells with pmiRNA-K-ras. In vivo, electroporation has proven to be a simple and efficient delivery method for local administration of pmiRNA-K-ras molecules into LoVo tumors. This therapy shows pronounced antitumor effectiveness and has no side effects. The obtained results demonstrate that electrogene therapy with miRNA-K-ras molecules can be potential therapeutic strategy for treatment of colorectal cancers harboring K-ras mutations. © 2010 Nature Publishing Group All rights reserved.

A review of Deeds of Company Arrangement

Deeds of company arrangement ('DOCAs') under Part 5.3A of the Corporations Act appear be something of a limited success. However, the use and outcomes of DOCAs raise legitimate questions as to whether the level of returns currently being achieved for creditors might be improved by legislative reform. The 2013 ARITA Terry Taylor Scholarship project entailed a review of a random sample of executed DOCAs effectuated between 1 August 2012 and 31 July 2013. This review was undertaken with the intention of producing a ‘snapshot’ of current trends and outcomes of the use of DOCAs in practice – ie, average (or typical) rates of dividends paid, what DOCAs customarily achieve, the profile of the companies executing DOCAs and the average duration of DOCAs. The purpose of this review was to empirically assess the use and effectiveness of DOCAs in order to inform the ongoing debate about the success or otherwise of Australia’s Part 5.3A voluntary administration regime (which recently marked its 20 year anniversary).

A sample review of Deeds of Company Arrangement under Part 5.3A of the Corporations Act

An empirical review of the operation of Part 5.3A of the Corporations Act 2001 (Cth) is timely given that Australia’s corporate rescue regime marked its 20 year anniversary in 2013. The research project culminating in this report was funded by the 2013 ARITA Terry Taylor Scholarship and entailed a review of a random sample of 72 executed DOCAs (and associated reports and returns) which were effectuated between 1 August 2012 and 31 July 2013. This sample review of DOCAs was undertaken with the intention of producing a ‘snapshot’ of current practices and trends pertaining to DOCAs – ie, average (or typical) rate of dividends paid, the outcomes or goals which DOCAs customarily achieve (eg, genuine company rescues, workouts, enhanced asset realisations or ‘quasi-liquidations’), the profile of the companies executing DOCAs and the average term/duration of DOCAs. The purpose and value of this sample review was to empirically assess the use and effectiveness of one important aspect of Part 5.3A and to further inform consideration and debate as to whether changes are warranted to Australia’s voluntary administration regime.

Simulation of ion flux distribution in conductive and nonconductive nanotip patterns

The distribution of flux of carbon-bearing cations over nanopatterned surfaces with conductive nanotips and nonconductive nanoislands is simulated using the Monte-Carlo technique. It is shown that the ion current is focused to nanotip surfaces when the negative substrate bias is low and only slightly perturbed at higher substrate biases. In the low-bias case, the mean horizontal ion displacement caused by the nanotip electric field exceeds 10 nm. However, at higher substrate biases, this value reduces down to 2 nm. In the nonconductive nanopattern case, the ion current distribution is highly nonuniform, with distinctive zones of depleted current density around the nanoislands. The simulation results suggest the efficient means to control ion fluxes in plasma-aided nanofabrication of ordered nanopatterns, such as nanotip microemitter structures and quantum dot or nanoparticle arrays. © World Scientific Publishing Company.

SiC-like phase and room-temperature photoluminescence of low-k SiOCH films

Carbon-doped hydrogenated silicon oxide (SiOCH) low-k films have been prepared using 13.56 MHz discharge in trimethylsilane (3MS) - oxygen gas mixtures at 3, 4, and 5 Torr sustained with RF power densities 1.3 - 2.6 W/cm2. The atomic structure of the SiOCH films appears to be a mixture the amorphous SiO2-like and the partially polycrystalline SiC-like phases. Results of the infra-red spectroscopy reflect the increment in the volume fraction of the SiC-like phase from 0.22 - 0.28 to 0.36 - 0.39 as the RF power increment. Steady-state near-UV laser-excited (364 nm wavelength, 40±2 mW) photoluminescence (PL) has been studied at room temperatures in the visible (1.8 eV - 3.1 eV) subrange of photon spectrum. Two main bands of the PL signal (at the photon energies of 2.5 - 2.6 eV and 2.8 - 2.9 eV) are observed. Intensities of the both bands are changed monotonically with RF power, whereas the bandwidth of ∼0.1 eV remains almost invariable. It is likely that the above lines are dumped by the non-radiative recombination involving E1-like centres in the amorphous-nanocrystalline SiC-like phases. Such explanation of the PL intensity dependences on the RF power density is supported by results of experimental studies of defect states spectrum in bandgap of the SiOCH films.

Nano-scale morphology and electron spectrum of defect states in low-k SiOCH films

Results of experimental investigations on the relationship between nanoscale morphology of carbon doped hydrogenated silicon-oxide (SiOCH) low-k films and their electron spectrum of defect states are presented. The SiOCH films have been deposited using trimethylsilane (3MS) - oxygen mixture in a 13.56 MHz plasma enhanced chemical vapor deposition (PECVD) system at variable RF power densities (from 1.3 to 2.6 W/cm2) and gas pressures of 3, 4, and 5 Torr. The atomic structure of the SiOCH films is a mixture of amorphous-nanocrystalline SiO2-like and SiC-like phases. Results of the FTIR spectroscopy and atomic force microscopy suggest that the volume fraction of the SiC-like phase increases from ∼0.2 to 0.4 with RF power. The average size of the nanoscale surface morphology elements of the SiO2-like matrix can be controlled by the RF power density and source gas flow rates. Electron density of the defect states N(E) of the SiOCH films has been investigated with the DLTS technique in the energy range up to 0.6 eV from the bottom of the conduction band. Distinct N(E) peaks at 0.25 - 0.35 eV and 0.42 - 0.52 eV below the conduction band bottom have been observed. The first N(E) peak is identified as originated from E1-like centers in the SiC-like phase. The volume density of the defects can vary from 1011 - 1017 cm-3 depending on specific conditions of the PECVD process.

Reducing bubble defect on the outsole production process in the footwear manufacturing industry

The purpose of this study is to discover the significant factors causing the bubble defect on the outsoles manufactured by the Case Company. The bubble defect occurs approximately 1.5 per cent of the time or in 36 pairs per day. To understand this problem, experimental studies are undertaken to identify various factors such as injector temperature, mould temperature; that affects the production of waste. The work presented in this paper comprises a review of the relevant literature on the Six Sigma DMAIC improvement process, quality control tools, and the design of the experiments. After the experimentation following the Six Sigma process, the results showed that the defect occurred in approximately 0.5 per cent of the products or in 12 pairs per day; this decreased the production cost from 6,120 AUD per month to 2,040 AUD per month. This research aimed to reduce the amount of waste in men’s flat outsoles. Hence, the outcome of research presented in this paper should be used as a guide for applying the appropriate process for each type of outsole.

A vibrational spectroscopic study of the silicate mineral harmotome – (Ba,Na,K)1-2(Si,Al)8O16⋅6H2O – A natural zeolite

The mineral harmotome (Ba,Na,K)1-2(Si,Al)8O16⋅6H2O is a crystalline sodium calcium silicate which has the potential to be used in plaster boards and other industrial applications. It is a natural zeolite with catalytic potential. Raman bands at 1020 and 1102 cm−1 are assigned to the SiO stretching vibrations of three dimensional siloxane units. Raman bands at 428, 470 and 491 cm−1 are assigned to OSiO bending modes. The broad Raman bands at around 699, 728, 768 cm−1 are attributed to water librational modes. Intense Raman bands in the 3100 to 3800 cm−1 spectral range are assigned to OH stretching vibrations of water in harmotome. Infrared spectra are in harmony with the Raman spectra. A sharp infrared band at 3731 cm−1 is assigned to the OH stretching vibration of SiOH units. Raman spectroscopy with complimentary infrared spectroscopy enables the characterization of the silicate mineral harmotome.

Pharmaceutical company influences on medication prescribing and their potential impact on quality use of medicines

Background Pharmaceuticals are big business, reporting strong market growth year after year. The ‘gatekeepers’ of this market are prescribers of medicines, who are the major target of pharmaceutical companies, utilizing direct and indirect influences. Methods This paper draws on previous research investigating pharmaceutical company prescribing influences to develop a qualitative model demonstrating the synergism between commercial influences on prescribing. The generic model was used to explore a realistic but hypothetical scenario to ascertain the applicability of the model. Results and Discussion A generic influence model was developed. The model was readily able to be adapted to reflect a realistic practice scenario. Conclusion Prescriber awareness of the linkages between various seemingly separate marketing techniques could potentially improve medicines usage in an evidence-based practice paradigm.

Withholding and withdrawing life-sustaining treatment in a patient's best interests : Australian judicial deliberations

•Intractable disputes about withholding and withdrawing life-sustaining treatment from adults who lack capacity are rare but challenging. Judicial resolution may be needed in some of these cases. •A central concept for judicial (and clinical) decision making in this area is a patient's “best interests”. Yet what this term means is contested. •There is an emerging Supreme Court jurisprudence that sheds light on when life-sustaining treatment will, or will not, be judged to be in a patient's best interests. •Treatment that is either futile or overly burdensome is not in a patient's best interests. Although courts will consider patient and family wishes, they have generally deferred to the views of medical practitioners about treatment decisions.

Managing climate change ‘by the numbers’ in a UK energy company

This paper examines how ideas and practices of accounting come together in turning the abstract concept of climate change into a new non-financial performance measure in a large energy company in the UK. It develops the notion of ‘governmental management’ to explain how the firm’s carbon dioxide emissions were transformed into a new organisational object that could be made quantifiable, measureable and ultimately manageable because of the modern power of accounting in tying disciplinary subjectivities and objectivities together whilst operating simultaneously at the level of individual and the organisation. Examining these interrelations highlights the constitutive nature of accounting in creating not just new categories for accounting’s attention, but in turn new organisational knowledge and knowledge experts in the making up accounting for climate change. Significantly, it appears these new knowledge experts are no longer accountants: which may help explain accounting’s evolution into evermore spheres of influence as we increasingly choose to manage our world ‘by the numbers’.

Mechanical filtering for narrow-band hearing in the weta

This paper constitutes a major attempt to associate tympanic deflections with the mechanoreceptor organ location in an acoustic insect. The New Zealand tree weta (Hemideina thoracica) has tympanal ears located on each of the prothoracic tibiae. The tympana exhibit a sclerotized oval plate, membranous processes bulging out from the tibial cuticle and many loosely suspended ripples. We used microscanning laser Doppler vibrometry to determine how such a tympanal membrane vibrates in response to sound and whether the sclerotized region plays a role in hearing. The tympanum displays a single resonance at the calling frequency of the male, an unusual example of an insect tympana acting as a narrow bandpass filter. Both tympana resonate in phase with the stimulus and with each other. Histological sections show that the tympanal area is divided into two distinct regions, as in other ensiferans. An oval plate lies in the middle of a thickened region and is surrounded by a transparent and uniformly thin region. It is hinged dorsally to the tympanal rim and thus resembles the model of a ‘hinged flap’. The thickened region appears to act as a damping mass on the oscillation of the thin region, and vibration displacement is reduced in this area. The thinner area vibrates with higher amplitude, inducing mechanical pressure on the dorsal area adjacent to the crista acustica. We present a new model showing how the thickened region might confer a mechanical gain onto the activation of the crista acustica sensory neurons during the sound-induced oscillations.

Terrestrial locomotion of the New Zealand short-tailed bat Mystacina tuberculata and the common vampire bat Desmodus rotundus

Bats (Chiroptera) are generally awkward crawlers, but the common vampire bat (Desmodus rotundus) and the New Zealand short-tailed bat (Mystacina tuberculata) have independently evolved the ability to manoeuvre well on the ground. In this study we describe the kinematics of locomotion in both species, and the kinetics of locomotion in M. tuberculata. We sought to determine whether these bats move terrestrially the way other quadrupeds do, or whether they possess altogether different patterns of movement on the ground than are observed in quadrupeds that do not fly. Using high-speed video analyses of bats moving on a treadmill, we observed that both species possess symmetrical lateral-sequence gaits similar to the kinematically defined walks of a broad range of tetrapods. At high speeds, D. rotundus use an asymmetrical bounding gait that appears to converge on the bounding gaits of small terrestrial mammals, but with the roles of the forelimbs and hindlimbs reversed. This gait was not performed by M. tuberculata. Many animals that possess a single kinematic gait shift with increasing speed from a kinetic walk (where kinetic and potential energy of the centre of mass oscillate out of phase from each other) to a kinetic run (where they oscillate in phase). To determine whether the single kinematic gait of M. tuberculata meets the kinetic definition of a walk, a run, or a gait that functions as a walk at low speed and a run at high speed, we used force plates and high-speed video recordings to characterize the energetics of the centre of mass in that species. Although oscillations in kinetic and potential energy were of similar magnitudes, M. tuberculata did not use pendulum-like exchanges of energy between them to the extent that many other quadrupedal animals do, and did not transition from a kinetic walk to kinetic run with increasing speed. The gait of M. tuberculata is kinematically a walk, but kinetically run-like at all speeds.