Targeting cancer with a lupus autoantibody

Systemic lupus erythematosus (SLE) is distinct among autoimmune diseases because of its association with circulating autoantibodies reactive against host DNA. The precise role that anti-DNA antibodies play in SLE pathophysiology remains to be elucidated, and potential applications of lupus autoantibodies in cancer therapy have not previously been explored. We report the unexpected finding that a cell-penetrating lupus autoantibody, 3E10, has potential as a targeted therapy for DNA repair–deficient malignancies. We find that 3E10 preferentially binds DNA single-strand tails, inhibits key steps in DNA single-strand and double-strand break repair, and sensitizes cultured tumor cells and human tumor xenografts to DNA-damaging therapy, including doxorubicin and radiation. Moreover, we demonstrate that 3E10 alone is synthetically lethal to BRCA2-deficient human cancer cells and selectively sensitizes such cells to low-dose doxorubicin. Our results establish an approach to cancer therapy that we expect will be particularly applicable to BRCA2-related malignancies such as breast, ovarian, and prostate cancers. In addition, our findings raise the possibility that lupus autoantibodies may be partly responsible for the intrinsic deficiencies in DNA repair and the unexpectedly low rates of breast, ovarian, and prostate cancers observed in SLE patients. In summary, this study provides the basis for the potential use of a lupus anti-DNA antibody in cancer therapy and identifies lupus autoantibodies as a potentially rich source of therapeutic agents.

RF magnetron sputtering deposition of bioactive Ca-P-based coatings on Ti-6Al-4V alloy

RF magnetron concurrent sputtering of Hydroxyapatite and Ti forming functionally graded calcium phosphate-based composite bioactive films on Ti-6Al-4V orthopedic alloy is reported. Calcium oxide phosphate (4CaO•P2O5) is the main crystalline phase. In vitro cell culturing tests suggest outstanding biocompatibility of the Ca-P-Ti films. Images of the plasma-enhanced sputtering processes and cell culturing are presented and discussed.

p-type doping of ZnO by means of high-density inductively coupled plasmas

A custom-designed inductively coupled plasma assisted radio-frequency magnetron sputtering deposition system has been used to fabricate N-doped p-type ZnO (ZnO:N) thin films on glass substrates from a sintered ZnO target in a reactive Ar + N2 gas mixture. X-ray diffraction and scanning electron microscopy analyses show that the ZnO:N films feature a hexagonal crystal structure with a preferential (002) crystallographic orientation and grow as vertical columnar structures. Hall effect and X-ray photoelectron spectroscopy analyses show that N-doped ZnO thin films are p-type with a hole concentration of 3.32 × 1018 cm- 3 and mobility of 1.31 cm2 V- 1 s- 1. The current-voltage measurement of the two-layer structured ZnO p-n homojunction clearly reveals the rectifying ability of the p-n junction. The achievement of p-type ZnO:N thin films is attributed to the high dissociation ability of the high-density inductively coupled plasma source and effective plasma-surface interactions during the growth process.

Aluminum-assisted crystallization and p-type doping of polycrystalline Si

Aluminum-doped p-type polycrystalline silicon thin films have been synthesized on glass substrates using an aluminum target in a reactive SiH 4+Ar+H2 gas mixture at a low substrate temperature of 300∈°C through inductively coupled plasma-assisted RF magnetron sputtering. In this process, it is possible to simultaneously co-deposit Si-Al in one layer for crystallization of amorphous silicon, in contrast to the conventional techniques where alternating metal and amorphous Si layers are deposited. The effect of aluminum target power on the structural and electrical properties of polycrystalline Si films is analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and Hall-effect analysis. It is shown that at an aluminum target power of 100 W, the polycrystalline Si film features a high crystalline fraction of 91%, a vertically aligned columnar structure, a sheet resistance of 20.2 kΩ/□ and a hole concentration of 6.3×1018 cm-3. The underlying mechanism for achieving the semiconductor-quality polycrystalline silicon thin films at a low substrate temperature of 300∈°C is proposed.

Multi-stage collapse events in the South Soufrière Hills, Montserrat as recorded in marine sediment cores

We present new evidence for sector collapses of the South Soufrière Hills (SSH) edifice, Montserrat during the mid-Pleistocene. High-resolution geophysical data provide evidence for sector collapse, producing an approximately 1 km3 submarine collapse deposit to the south of SSH. Sedimentological and geochemical analyses of submarine deposits sampled by sediment cores suggest that they were formed by large multi-stage flank failures of the subaerial SSH edifice into the sea. This work identifies two distinct geochemical suites within the SSH succession on the basis of trace-element and Pb-isotope compositions. Volcaniclastic turbidites in the cores preserve these chemically heterogeneous rock suites. However, the subaerial chemostratigraphy is reversed within the submarine sediment cores. Sedimentological analysis suggests that the edifice failures produced high-concentration turbidites and that the collapses occurred in multiple stages, with an interval of at least 2 ka between the first and second failure. Detailed field and petrographical observations, coupled with SEM image analysis, shows that the SSH volcanic products preserve a complex record of magmatic activity. This activity consisted of episodic explosive eruptions of andesitic pumice, probably triggered by mafic magmatic pulses and followed by eruptions of poorly vesiculated basaltic scoria, and basaltic lava flows.

Health Law in Australia [Second Edition]

Health Law in Australia is the country’s leading text in this area and was the first book to deal with health law on a comprehensive national basis. In this important field that continues to give rise to challenges for society Health Law in Australia takes a logical, structured approach to explain the breadth of this area of law across all Australian jurisdictions. By covering all the major areas in this diverse field, Health Law in Australia enhances the understanding of the discipline as a whole. Beginning with an exploration of the general principles of health law, including chapters on “Negligence”, “Children and Consent to Medical Treatment”, and “Medical Confidentiality and Patient Privacy”, the book goes on to consider beginning-of-life and end-of-life issues before concluding with chapters on emerging areas in health law, such as biotechnology, genetic technologies and medical research. The contributing authors are national leaders who are specialists in these areas of health law and who can share with readers the results of their research. Health Law in Australia has been written for both legal and health audiences and is essential reading for undergraduate and postgraduate students, researchers and scholars in the disciplines of law, health and medicine, as well as health and legal practitioners, government departments and bodies in the health area, and private health providers.

Controlled electroluminescence of n-ZnMgO/p-GaN light-emitting diodes

Effective control of room-temperature electroluminescence of n-ZnMgO/p-GaN light-emitting diodes (LEDs) over both emission intensity and wavelength is demonstrated. With varied Mg concentration, the intensity of LEDs in the near-ultraviolet region is increased due to the effective radiative recombination in the ZnMgO layer. Furthermore, the emission wavelength is shifted to the green/yellow spectral region by employing an indium-tin-oxide thin film as the dopant source, where thermally activated indium diffusion creates extra deep defect levels for carrier recombination. These results clearly demonstrate the effectiveness of controlled metal incorporation in achieving high energy efficiency and spectral tunability of the n-ZnMgO/p-GaN LED devices.

Molecular basis for lysine specificity in the yeast ubiquitin-conjugating enzyme Cdc34

Ubiquitin (Ub)-conjugating enzymes (E2s) and ubiquitin ligases (E3s) catalyze the attachment of Ub to lysine residues in substrates and Ub during monoubiquitination and polyubiquitination. Lysine selection is important for the generation of diverse substrate-Ub structures, which provides versatility to this pathway in the targeting of proteins to different fates. The mechanisms of lysine selection remain poorly understood, with previous studies suggesting that the ubiquitination site(s) is selected by the E2/E3-mediated positioning of a lysine(s) toward the E2/E3 active site. By studying the polyubiquitination of Sic1 by the E2 protein Cdc34 and the RING E3 Skp1/Cul1/F-box (SCF) protein, we now demonstrate that in addition to E2/E3-mediated positioning, proximal amino acids surrounding the lysine residues in Sic1 and Ub are critical for ubiquitination. This mechanism is linked to key residues composing the catalytic core of Cdc34 and independent of SCF. Changes to these core residues altered the lysine preference of Cdc34 and specified whether this enzyme monoubiquitinated or polyubiquitinated Sic1. These new findings indicate that compatibility between amino acids surrounding acceptor lysine residues and key amino acids in the catalytic core of ubiquitin-conjugating enzymes is an important mechanism for lysine selection during ubiquitination.

Alignment and differences between the Australian Water Accounting Standard and the Water Accounting Framework for the Minerals Industry

In 2012, the Bureau of Meteorology under the banner of the Water Accounting Standards Board released the Australian Water Accounting Standard 1 (AWAS 1). This standard has been in development since 2007 with key milestones being the release of the Preliminary Australian Water Accounting Standard in 2009, and the exposure draft of the Australian Water Accounting Standard in 2010. Throughout this period, the Minerals Council of Australia’s Water Accounting Framework has developed concurrently with the Australian standards and the standards have informed elements of the framework. However, the framework is not identical to the standard as the objectives between the two are different. The objective of the Water Accounting Framework is to create consistency in water reporting of the minerals industry and to assist companies reporting to corporate sustainability initiatives. The objective of AWAS 1 is to provide information to water management bodies to facilitate decisions about the allocation of water resources. Companies are to report on an annual basis, not only physical flows of water but contractual requirements to supply and obtain water, regardless of whether the transaction has been fulfilled in the reporting period. In contrast, the Water Accounting Framework only reports on flows that have physically happened. The paper will provide summary information on aspects of AWAS 1 that are most relevant to the minerals industry, show the alignment and differences between AWAS 1 and the Water Accounting Framework and explain how to obtain the information for the AWAS 1 reporting statements.

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.

A high mobility P-type DPP-thieno[3,2-b]thiophene copolymer for organic thin-film transistors

A copolymer comprising 1,4-diketopyrrolo[3,4-c]pyrrole (DPP) and thieno[3,2-b]thiophene moieties, PDBT-co-TT, shows high hole mobility of up to 0.94 cm2 V-1 s-1 in organic thin-film transistors. The strong intermolecular interactions originated from π-π stacking and donor-acceptor interaction lead to the formation of interconnected polymer networks having an ordered lamellar structure, which have established highly efficient pathways for charge carrier transport.

Synthesis of diketopyrrolopyrrole based copolymers via the direct arylation method for p-channel and ambipolar OFETs

In this paper, we have synthesized two novel diketopyrrolopyrrole (DPP) based donor-acceptor (D-A) copolymers poly{3,6-dithiophene-2-yl-2,5-di(2-octyl)- pyrrolo[3,4-c]pyrrole-1,4-dione-alt-1,5-bis(dodecyloxy)naphthalene} (PDPPT-NAP) and poly{3,6-dithiophene-2-yl-2,5-di(2-butyldecyl)-pyrrolo[3,4-c]pyrrole-1,4- dione-alt-2-dodecyl-2H-benzo[d][1,2,3]triazole} (PDPPT-BTRZ) via direct arylation organometallic coupling. Both copolymers contain a common electron withdrawing DPP building block which is combined with electron donating alkoxy naphthalene and electron withdrawing alkyl-triazole comonomers. The number average molecular weight (Mn) determined by gel permeation chromatography (GPC) for polymer PDPPT-NAP is around 23 400 g mol-1 whereas for polymer PDPPT-BTRZ it is 18 600 g mol-1. The solid state absorption spectra of these copolymers show a wide range of absorption from 400 nm to 1000 nm with optical band gaps calculated from absorption cut off values in the range of 1.45-1.30 eV. The HOMO values determined for PDPPT-NAP and PDPPT-BTRZ copolymers from photoelectron spectroscopy in air (PESA) data are 5.15 eV and 5.25 eV respectively. These polymers exhibit promising p-channel and ambipolar behaviour when used as an active layer in organic thin-film transistor (OTFT) devices. The highest hole mobility measured for polymer PDPPT-NAP is around 0.0046 cm2 V-1 s-1 whereas the best ambipolar performance was calculated for PDPPT-BTRZ with a hole and electron mobility of 0.01 cm2 V-1 s-1 and 0.006 cm2 V-1 s-1.

A critical success factors model for enterprise resource planning implementation

Enterprise Resource Planning (ERP) systems are integrated enterprise-wide standard information systems that automate all aspects of an organisations’ business processes. The ERP philosophy is that business systems incorporating sales, marketing, manufacturing, distribution, personnel and finance modules can be supported by a single integrated system with all of the company’s data captured in a central database. The ERP packages of vendors such as SAP, Baan, J.D. Edwards and Intentia represent more than a common systems platform for a business. They prescribe information blueprints of how organisation’s business processes should operate. In this paper, the scale and strategic importance of ERP systems is identified and the problem of ERP implementation is defined. Five company examples are analysed using a Critical Success Factors (CSFs) theoretical framework. The paper offers a framework for managers which provides the basis for developing an ERP implementation strategy. The case analysis identifies different approaches to ERP implementation, highlights the critical role of legacy systems in influencing the implementation process, and identifies the importance of business process change and software configuration in addition to factors already cited in the literature such as top management support and communication. The implications of the results and future research opportunities are outlined.

Mandatory Reporting Laws and Identification of Child Abuse and Neglect: Consideration of Differential Maltreatment Types, and a Cross-Jurisdictional Analysis of Child Sexual Abuse Reports

Mandatory reporting laws have been created in many jurisdictions as a way of identifying cases of severe child maltreatment on the basis that cases will otherwise remain hidden. These laws usually apply to all four maltreatment types. Other jurisdictions have narrower approaches supplemented by differential response systems, and others still have chosen not to enact mandatory reporting laws for any type of maltreatment. In scholarly research and normative debates about mandatory reporting laws and their effects, the four major forms of child maltreatment—physical abuse, sexual abuse, emotional abuse, and neglect—are often grouped together as if they are homogenous in nature, cause, and consequence. Yet, the heterogeneity of maltreatment types, and different reporting practices regarding them, must be acknowledged and explored when considering what legal and policy frameworks are best suited to identify and respond to cases. A related question which is often conjectured upon but seldom empirically explored, is whether reporting laws make a difference in case identification. This article first considers different types of child abuse and neglect, before exploring the nature and operation of mandatory reporting laws in different contexts. It then posits a differentiation thesis, arguing that different patterns of reporting between both reporter groups and maltreatment types must be acknowledged and analysed, and should inform discussions and assessments of optimal approaches in law, policy and practice. Finally, to contribute to the evidence base required to inform discussion, this article conducts an empirical cross-jurisdictional comparison of the reporting and identification of child sexual abuse in jurisdictions with and withoutmandatory reporting, and concludes that mandatory reporting laws appear to be associated with better case identification.