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.

Identification of optimal epitopes for Plasmodium falciparum rapid diagnostic tests that target histidine-rich proteins 2 and 3

Rapid diagnostic tests (RDTs) represent important tools to diagnose malaria infection. To improve understanding of the variable performance of RDTs that detect the major target in Plasmodium falciparum, namely, histidine-rich protein 2 (HRP2), and to inform the design of better tests, we undertook detailed mapping of the epitopes recognized by eight HRP-specific monoclonal antibodies (MAbs). To investigate the geographic skewing of this polymorphic protein, we analyzed the distribution of these epitopes in parasites from geographically diverse areas. To identify an ideal amino acid motif for a MAb to target in HRP2 and in the related protein HRP3, we used a purpose-designed script to perform bioinformatic analysis of 448 distinct gene sequences from pfhrp2 and from 99 sequences from the closely related gene pfhrp3. The frequency and distribution of these motifs were also compared to the MAb epitopes. Heat stability testing of MAbs immobilized on nitrocellulose membranes was also performed. Results of these experiments enabled the identification of MAbs with the most desirable characteristics for inclusion in RDTs, including copy number and coverage of target epitopes, geographic skewing, heat stability, and match with the most abundant amino acid motifs identified. This study therefore informs the selection of MAbs to include in malaria RDTs as well as in the generation of improved MAbs that should improve the performance of HRP-detecting malaria RDTs.

Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests

Background Accurate diagnosis is essential for prompt and appropriate treatment of malaria. While rapid diagnostic tests (RDTs) offer great potential to improve malaria diagnosis, the sensitivity of RDTs has been reported to be highly variable. One possible factor contributing to variable test performance is the diversity of parasite antigens. This is of particular concern for Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-detecting RDTs since PfHRP2 has been reported to be highly variable in isolates of the Asia-Pacific region. Methods The pfhrp2 exon 2 fragment from 458 isolates of P. falciparum collected from 38 countries was amplified and sequenced. For a subset of 80 isolates, the exon 2 fragment of histidine-rich protein 3 (pfhrp3) was also amplified and sequenced. DNA sequence and statistical analysis of the variation observed in these genes was conducted. The potential impact of the pfhrp2 variation on RDT detection rates was examined by analysing the relationship between sequence characteristics of this gene and the results of the WHO product testing of malaria RDTs: Round 1 (2008), for 34 PfHRP2-detecting RDTs. Results Sequence analysis revealed extensive variations in the number and arrangement of various repeats encoded by the genes in parasite populations world-wide. However, no statistically robust correlation between gene structure and RDT detection rate for P. falciparum parasites at 200 parasites per microlitre was identified. Conclusions The results suggest that despite extreme sequence variation, diversity of PfHRP2 does not appear to be a major cause of RDT sensitivity variation.

Herpes simplex 2 risk among women in a polygynous setting in rural West Africa

OBJECTIVES: To determine risk factors for herpes simplex 2 (HSV2) infection in women in a polygynous rural Gambian population. METHODS: Data from women who participated in a cross-sectional survey of reproductive health were matched to their own and, for women who had been or were married (ever-married), their spouses' data collected in a cross-sectional survey of fertility interests, including information on marital histories. RESULTS: Data were available on 150 never-married and 525 ever-married women. HSV2 prevalence was 16% amongst never-married women and 36% amongst ever-married women. For ever-married women, their own personal characteristics (age, ethnicity and genital cutting status) and events from their husbands' marriage history were important determinants of HSV2 infection. Women whose husbands married for the first time over age 35 were at greater risk than women whose husbands married by age 24 [odds ratio (OR) 2.72, 95% confidence interval (CI) 1.20-6.10]. Women whose husband reported interest in a new marriage were more likely to be HSV2 positive (OR 1.91, 95% CI 1.18-3.09). Women whose husbands were currently monogamous but had had previous marriages (OR 2.76, 95% CI 1.30-5.88) and women in currently polygynous marriages (OR 2.88, 95% CI 1.66-5.01) were three times as likely to be HSV2 positive as women who were their husband's only wife ever. CONCLUSION: Much transmission of HSV2 in this setting occurs within marriage where opportunity for personal protection is limited. High levels of transmission within marriage may undermine the impact of sexual behaviour change programmes aiming to reduce HSV2 and HIV incidence and complicate their evaluation.

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.

Poly(2,5-bis(2-octyldodecyl)-3,6-di(furan-2-yl)-2,5-dihydro-pyrrolo[3,4-c] pyrrole-1,4-dione-co-thieno[3,2-b]thiophene): A high performance polymer semiconductor for both organic thin film transistors and organic photovoltaics

A new diketopyrrolopyrrole (DPP)-containing donor-acceptor polymer, poly(2,5-bis(2-octyldodecyl)-3,6-di(furan-2-yl)-2,5-dihydro-pyrrolo[3,4-c] pyrrole-1,4-dione-co-thieno[3,2-b]thiophene) (PDBF-co-TT), is synthesized and studied as a semiconductor in organic thin film transistors (OTFTs) and organic photovoltaics (OPVs). High hole mobility of up to 0.53 cm 2 V -1 s -1 in bottom-gate, top-contact OTFT devices is achieved owing to the ordered polymer chain packing and favoured chain orientation, strong intermolecular interactions, as well as uniform film morphology of PDBF-co-TT. The optimum band gap of 1.39 eV and high hole mobility make this polymer a promising donor semiconductor for the solar cell application. When paired with a fullerene acceptor, PC 71BM, the resulting OPV devices show a high power conversion efficiency of up to 4.38% under simulated standard AM1.5 solar illumination.

3,6-Di(furan-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione and bithiophene copolymer with rather disordered chain orientation showing high mobility in organic thin film transistors

Pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione or diketopyrrolopyrrole (DPP) is a useful electron-withdrawing fused aromatic moiety for the preparation of donor-acceptor polymers as active semiconductors for organic electronics. This study uses a DPP-furan-containing building block, 3,6-di(furan-2-yl)pyrrolo[3,4- c]pyrrole-1,4(2H,5H)-dione (DBF), to couple with a 2,2′-bithiophene unit, forming a new donor-acceptor copolymer, PDBFBT. Compared to its structural analogue, 3,6-di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (DBT), DBF is found to cause blue shifts of the absorption spectra both in solution and in thin films and a slight reduction of the highest occupied molecular orbital (HOMO) energy level of the resulting PDBFBT. Despite the fact that its thin films are less crystalline and have a rather disordered chain orientation in the crystalline domains, PDBFBT shows very high hole mobility up to 1.54 cm 2 V-1 s-1 in bottom-gate, top-contact organic thin film transistors.

Solution processable poly(2,5-dialkyl-2,5-dihydro-3,6-di-2-thienyl- pyrrolo[3,4-c]pyrrole-1,4-dione) for ambipolar organic thin film transistors

Solution processable diketopyrrolopyrrole (DPP)-bithiophene polymers (PDBT) with long branched alkyl side chains on the DPP unit are synthesized. These polymers have favourable highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels for the injection and transport of both holes and electrons. Organic thin film transistors (OTFTs) using these polymers as semiconductors and gold as source/drain electrodes show typical ambipolar characteristics with very well balanced high hole and electron mobilities (μ h = 0.024 cm 2 V -1 s -1 and μ e = 0.056 cm 2 V -1 s -1). These simple and high-performing polymers are promising materials for ambipolar organic thin film transistors for low-cost CMOS-like logic circuits.

Electron-accepting conjugated materials based on 2-Vinyl-4,5- dicyanoimidazoles for application in organic electronics

We report the Heck coupling of 2-vinyl-4,5-dicyanoimidazole (vinazene) with selected di- and trihalo aromatics in an effort to prepare linear and branched electron-accepting conjugated materials for application in organic electronics. By selecting the suitable halo-aromatic moiety, it is possible to tune the HOMO - LUMO energy levels, absorption, and emission properties for a specific application. In this regard, materials with strong photoluminescence from blue → green → red are reported that may have potential application in organic light-emitting diodes (OLEDs). Furthermore, derivatives with strong absorption in the visible spectrum, coupled with favorable HOMO-LUMO levels, have been used to prepare promising organic photovoltaic devices (OPVs) when combined with commercially available semiconducting donor polymers.

4-hexylbithieno[3,2-b:2′3′-e]pyridine: An efficient electron-accepting unit in fluorene and indenofluorene copolymers for light-emitting devices

4-Hexylbithienopyridine has been prepared as a novel electron-accepting monomer for conjugated polymers. To test its electronic properties, alternating copolymers with fluorene and indenofluorene polymers have been prepared. The copolymers displayed reduction potentials about 0.5 V lower than for the corresponding fluorene and indenofluorene homopolymers, indicating much improved electron-accepting properties. Analysis of the microscopic morphology of thin films of the copolymers by AFM shows that they lack the extensive supramolecular order seen with the homopolymers, which is attributed to the bithienopyridine units disrupting the π-stacking. LEDs using these polymers as the emitting layer produce blue-green emission with low turn-on voltages with aluminum electrodes confirming their improved electron affinity. The indenofluorene copolymer displayed an irreversible red shift in emission at high voltages, which is attributed to oxidation of the indenofluorene units. This red shift occurred at higher potentials than for indenofluorene homopolymers in LEDs, suggesting that the heterocyclic moieties offer some protection against electrically promoted oxidation.

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.

The dynamics of cellular automata on 2-manifolds is affected by topology

In this paper, we demonstrate that the distribution of Wolfram classes within a cellular automata rule space in the triangular tessellation is not consistent across different topological general. Using a statistical mechanics approach, cellular automata dynamical classes were approximated for cellular automata defined on genus-0, genus-1 and genus-2 2-manifolds. A distribution-free equality test for empirical distributions was applied to identify cases in which Wolfram classes were distributed differently across topologies. This result implies that global structure and local dynamics contribute to the long term evolution of cellular automata.

Too cool for homeschool? Accessing underground unschoolers with Web 2.0

There is a new type of home education parent challenging long-held assumptions about homeschooling (cf. Morton 2012). These parents are well educated (cf. Beck 2010) but have chosen to eschew the social and cultural capital (Bourdieu & Wacquant 1992) of school in favour of some- thing completely different. They are unschoolers, which involves ‘allow- ing children as much freedom to learn in the world as their parents can possibly bear’ (cf. Holt & Farenga 2003: 238). This chapter presents the approach taken by one researcher to explore the reasons families choose unschooling. These families can be difficult to access, because they often fail to register with home education units and thus remain outside the education system (cf. Townsend 2012). Their lack of registration makes them largely invisible, affecting their ability to make an important contribution to debates around education. In spite of this invisibility, many unschoolers are keen to talk to researchers to increase wider understanding of unschooling.

The Spartan-3E Tutorial 1 : Introduction to FPGA Programming, Version 2.0

This tutorial is designed to help new users become familiar with using the Spartan-3E board. The tutorial steps through: writing a small program in VHDL which carries out simple combinational logic; connecting the program inputs and outputs to the switches, buttons and LEDs on the Spartan-3E board; downloading the program to the Spartan-3E board using version 14.7 of the Xilinx ISE; and simulating the program using the iSim Simulator.

Plagiarism 2.0 : the new economy of academic dishonesty

As a writer, teacher and scholar of ‘the knowledge economy’ in the broadest sense, plagiarism fascinates me. I first encountered plagiarism in my Year 12 English class. We had been working for weeks writing poems and had submitted them to our teacher Mr How for assessment. Mr How was generally a pleasant individual who I remember as one of my favourite school teachers; however, he did not suffer fools easily. The time arrived for each of us to read our work to the class. Year 12 poetry being what it usually is, most of our efforts tended to blur into an angsty, slightly pretentious, self-important mess (similar to staff meetings in many university departments). However, one student’s poem stood out. It was emotive, insightful and economical in its use of language … and best of all, it did not suck! The poem’s author was one of the class’ biggest jocks, and not usually one to display such sensitivity, so we were all a little taken aback by what we were hearing. Stunned silence! At the poem’s conclusion, Mr How congratulated the student on such an excellent effort and produced a copy of the collected works of Emily Dickenson (if I remember correctly) from under his desk. He asked the student to turn to a page he had marked and recite the poem printed there. It was, of course, the same one the student had passed off as his. This time, there was no stunned silence: just the sound of remorseful sobs from our jock-poet-plagiarist who had been exposed in front of his classmates.