Grave of Josef Molling; Germany.

Josef Molling committed suicide. He had financial problems, either embezzelment from the Prussian State Lottery or over an aircraft plant.

Adenoviral Gene Therapy for Advanced Head and Neck Cancer

Advanced stage head and neck cancers (HNC) with distant metastasis, as well as prostate cancers (PC), are devastating diseases currently lacking efficient treatment options. One promising developmental approach in cancer treatment is the use of oncolytic adenoviruses, especially in combination therapy with conventional cancer therapies. The safety of the approach has been tested in many clinical trials. However, antitumor efficacy needs to be improved in order to establish oncolytic viruses as a viable treatment alternative. To be able to test in vivo the effects on anti-tumor efficiency of a multimodal combination therapy of oncolytic adenoviruses with the standard therapeutic combination of radiotherapy, chemotherapy and Cetuximab monoclonal antibody (mAb), a xenograft HNC tumor model was developed. This model mimics the typical clinical situation as it is initially sensitive to cetuximab, but resistance develops eventually. Surprisingly, but in agreement with recent findings for chemotherapy and radiotherapy, a higher proportion of cells positive for HNC cancer stem cell markers were found in the tumors refractory to cetuximab. In vitro as well as in vivo results found in this study support the multimodal combination therapy of oncolytic adenoviruses with chemotherapy, radiotherapy and monoclonal antibody therapy to achieve increased anti-tumor efficiency and even complete tumor eradication with lower treatment doses required. In this study, it was found that capsid modified oncolytic viruses have increased gene transfer to cancer cells as well as an increased antitumor effect. In order to elucidate the mechanism of how oncolytic viruses promote radiosensitization of tumor cells in vivo, replicative deficient viruses expressing several promising radiosensitizing viral proteins were tested. The results of this study indicated that oncolytic adenoviruses promote radiosensitization by delaying the repair of DNA double strand breaks in tumor cells. Based on the promising data of the first study, two tumor double-targeted oncolytic adenoviruses armed with the fusion suicide gene FCU1 or with a fully human mAb specific for human Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) were produced. FCU1 encodes a bifunctional fusion protein that efficiently catalyzes the direct conversion of 5-FC, a relatively nontoxic antifungal agent, into the toxic metabolites 5-fluorouracil and 5-fluorouridine monophosphate, bypassing the natural resistance of certain human tumor cells to 5-fluorouracil. Anti-CTLA4 mAb promotes direct killing of tumor cells via apoptosis and most importantly immune system activation against the tumors. These armed oncolytic viruses present increased anti-tumor efficacy both in vitro and in vivo. Furthermore, by taking advantage of the unique tumor targeted gene transfer of oncolytic adenoviruses, functional high tumor titers but low systemic concentrations of the armed proteins were generated. In addition, supernatants of tumor cells infected with Ad5/3-24aCTLA4, which contain anti-CTLA4 mAb, were able to effectively immunomodulate peripheral blood mononuclear cells (PBMC) of cancer patients with advanced tumors. -- In conclusion, the results presented in this thesis suggest that genetically engineered oncolytic adenoviruses have great potential in the treatment of advanced and metastatic HNC and PC.

Studio portrait of the six daughters of Solomon and Emilie Kohnberger: (l-r) Laura, Irene, Johanna, Melanie, Hermine and Martha.

Laura (1878-1917) died during a flu epidemic. She married Sigmund Stiassny and had two children, Lisbeth (Gersuny) (1900-1986) and Walter (1902-1912) who died of a ruptured appendix.

Metal-organic framework structures - how closely are they related to classical inorganic structures?

Metal-organic frameworks (MOFs) have emerged as an important family of compounds for which new properties are increasingly being found. The potential for such compounds appears to be immense, especially in catalysis, sorption and separation processes. In order to appreciate the properties and to design newer frameworks it is necessary to understand the structures from a fundamental perspective. The use of node, net and vertex symbols has helped in simplifying some of the complex MOF structures. Many MOF structures are beginning to be described as derived from inorganic structures. In this tutorial review, we have provided the basics of the node, the net and the vertex symbols and have explained some of the MOF structures. In addition, we have also attempted to provide some leads towards designing newer structures/topologies.

A genome-wide association study of sleep habits and insomnia

Several aspects of sleep behavior such as timing, duration and quality have been demonstrated to be heritable. To identify common variants that influence sleep traits in the population, we conducted a genome-wide association study of six sleep phenotypes assessed by questionnaire in a sample of 2,323 individuals from the Australian Twin Registry. Genotyping was performed on the Illumina 317, 370, and 610K arrays and the SNPs in common between platforms were used to impute non-genotyped SNPs. We tested for association with more than 2,000,000 common polymorphisms across the genome. While no SNPs reached the genome-wide significance threshold, we identified a number of associations in plausible candidate genes. Most notably, a group of SNPs in the third intron of the CACNA1C gene ranked as most significant in the analysis of sleep latency (P = 1.3 x 10(-)(6)). We attempted to replicate this association in an independent sample from the Chronogen Consortium (n = 2,034), but found no evidence of association (P = 0.73). We have identified several other suggestive associations that await replication in an independent sample. We did not replicate the results from previous genome-wide analyses of self-reported sleep phenotypes after correction for multiple testing.

Alternative fruit fly management for market access for apples

Difficulty with control of Queensland fruit fly with four cultivars of apples on the Granite Belt, Qld. Warnings that the insecticides dimethoate & fenthion might be removed from the market for apples, had been current for several years. Dimethoate was widely used as a post harvest control measure as well as an in-field treatment. Fenthion also had and still has in-field usage. The project attempted to find a replacement for these control measures.

Flotation of calcareous Mussorie phosphate ore

Separation of Mussorie rock phosphate (P2O5 = 20%) from Uttar Pradesh, India, containing pyrite, calcite and other carbonaceous impurities by flotation has been successfully attempted to upgrade the phosphate values. Based on Hallimond cell flotation results of single and synthetic mineral mixtures of calcite and apatite using oleic acid and potassium phosphate, conditions were obtained for the separation of calcite from apatite which is considered to be the most difficult step in the beneficiation of calcareous phosphates. Further studies using 250 g of the mineral (−60 +150 and −150 mesh fractions, deslimed) in laboratory size Fagergren subaeration machine employed a stagewise flotation viz. carbonaceous materials using terpineol, pyrite using potassium-ethyl xanthate and calcite using oleic acid respectively. Separation was, however, found to be unsatisfactory in the absence of a depressant. Among starch, hydrofluosilicic acid and dipotassium hydrogen phosphate, which were tried as depressants for apatite in the final flotation stage, dipotassium hydrogen phosphate proved to be superior to others. However, the tests with the above fractions did not yield the required grade. This was possibly due to insufficient liberation of the phosphate mineral from the ore body and different experimental conditions due to scale up operations. Experiments conducted using −200 mesh deslimed fractions has yielded an acceptable grade of 27.6% P2O5 with a recovery of about 60%. The results have been explained in terms of the specific adsorption characteristics of phosphate ions on apatite and the liberation size of the mineral.

Isohydric and anisohydric characterisation of vegetable crops. The classification of vegetables by their physiological responses to water stress

Research on the physiological response of crop plants to drying soils and subsequent water stress has grouped plant behaviours as isohydric and anisohydric. Drying soil conditions, and hence declining soil and root water potentials, cause chemical signals—the most studied being abscisic acid (ABA)—and hydraulic signals to be transmitted to the leaf via xylem pathways. Researchers have attempted to allocate crops as isohydric or anisohydric. However, different cultivars within crops, and even the same cultivars grown in different environments/climates, can exhibit both response types. Nevertheless, understanding which behaviours predominate in which crops and circumstances may be beneficial. This paper describes different physiological water stress responses, attempts to classify vegetable crops according to reported water stress responses, and also discusses implications for irrigation decision-making.

Grave of Josef Molling; Germany.

Josef Molling committed suicide. He had financial problems, either embezzelment from the Prussian State Lottery or over an aircraft plant.

Free convection heat transfer to mercury in vertical annuli

Data on free convection heat transfer to water and mercury are collected using a test rig in vertical annuli of three radii ratios, the walls of which are maintained at uniform temperatures. A theoretical analysis of the boundary layer equations has been attempted using local similarity transformation and double boundary layer approach. Correlations derived from the present theoretical analysis are compared with the analysis and the experimental data available in literature for non-metallic fluids and also with the present experimental data on water and mercury. Generalised correlations are set up for expressing the ratio of heat transferred by convection to the heat transferred by pure conduction and Nusselt's number, in terms of Grashof, Rayleigh and Prandtl numbers, based on the theoretical analysis and the present data on mercury and water. The present generalised correlations agree with the reported and present data for non-metallic fluids and liquid metals with an average deviation of 9% and maximum deviation of ± 13.7%.

Recruitment sources of brown trout identified by otolith trace element signatures.

This study examined whether element: Ca ratios within the otoliths of juvenile brown trout could provide accurate trace element signatures for specific natal tributaries, and attempted to match these to trace element natal signatures found within the otoliths of adult trout caught in the main stem rivers of the same catchment. The trace element signatures of juvenile trout otoliths were analysed from a sample of eight tributaries representing the main sub-catchments of the Motueka River catchment, New Zealand. Trace element signatures were determined using laser ablation inductively coupled plasma mass spectrometry, and differentiated using linear discriminant function analysis with an overall cross-validated classification success of 96.8%. Temporal stability in element: Ca ratios was investigated by repeat collections of juvenile fish over two years. Natal signatures from 11 of 23 adult trout sampled from the catchment main stems were matched to one of the eight tributary signatures showing recruitment sources to be spread relatively evenly throughout the catchment. This study demonstrates the potential of using otolith trace element analysis to determine the natal origins of freshwater fish within a catchment.

Beyond fecundity control: which weeds are most containable?

1. Eradication is often the preferred strategy in the management of new weed invasions, but recent research has shown that the circumstances under which eradication can be achieved are highly constrained. Containment is a component of an eradication strategy and also a management objective in its own right. Just as for eradication, containment of a weed invasion should be attempted only if it is considered feasible. However, very little guidance exists for the assessment of containment feasibility for weeds. 2. Numerous factors have been proposed as influencing feasibility of containment, but those that relate to the potential for management of dispersal pathways and timely detection of new foci of infestation appear to be critical. Theory suggests that the rate of spread is largely driven by long-distance dispersal (LDD). However, LDD is generally unpredictable and often occurs for species that do not appear to be adapted for it. Furthermore, many (if not most) LDD events fail to give rise to new infestations. 3. As the probability of colonisation is related to the numbers of propagules immigrating ('propagule pressure') at a point in the landscape, dispersal pathways that move relatively large numbers of propagules simultaneously and/or repeatedly should most enhance weed spread. It is these pathways whose potential for management has the greatest bearing upon containment feasibility. A key impediment to containment is undetected spread; this need not occur through LDD and is more likely to occur through dispersal to lesser distances. 4. Synthesis and applications. Feasibility of containment should be viewed in terms of the effort required to reduce weed spread rate, as well as the effectiveness of relevant management actions. Where dispersal vectors are not readily manageable and the probability of detection via structured and/or unstructured surveillance is low, a much greater reliance upon fecundity control will be needed to contain a weed. A combination of empirical and theoretical approaches should be used to develop and refine estimates of containment feasibility. Such estimates will aid decision-making with regard to whether to attempt to reduce weed spread and assist in prioritisation of different weeds for containment.

Effect of physiological and experiential state of Bactrocera tryoni flies on intra-tree foraging behavior for food (bacteria) and host fruit

Using caged guava trees in Queensland, Australia, provided with food and oviposition sites, the foraging behaviour of females of the tephritid Bactrocera tryoni was investigated in relation to hunger for protein, the presence or absence of bacteria as a source of protein, the degree of prior experience with host fruit and quality of host fruit for oviposition. One aim was to evaluate whether it is immature or mature B. tryoni females that are responsible for initially inoculating host fruit surfaces with "fruit-fly-type" bacteria, the odour of which is known to attract B. tryoni females. Three-week-old immature females provided with sucrose but deprived of protein from eclosion had a much greater propensity than 3-week-old protein-fed mature females to visit vials containing fruit-fly-type bacteria, irrespective of whether vials were associated with adjacent host fruit or not. In the absence of associated bacteria in vials, immature females had a much lower propensity than mature females to visit host fruit. In the presence of bacteria in vials, however, propensity of immature and mature females to visit fruit was about equal. Mature (but not immature) females were more inclined to visit fruit that ranked higher for oviposition (nectarines) than fruit that ranked lower (sweet oranges). Mature females that attempted oviposition during a single 3-min exposure period to a nectarine prior to release were much more likely to find a nectarine than were mature females naive to fruit or immature females with or without prior contact with fruit. Exposure to a nectarine before release did not affect the propensity of either mature or immature females to alight on an odourless visual model of a nectarine, however. As judged by numbers of leaves visited, protein-deprived immature females were more active than protein-fed mature females, irrespective of the sorts of resources on a tree. It was concluded that: the 1st B. tryoni females to arrive on the fruit of a host tree and therefore inoculate the fruit with fruit-fly-type bacteria were unlikely to be sexually immature, but to be mature as a result of having earlier acquired protein elsewhere; the odour of colonies of fruit-fly-type bacteria when associated with host fruit attracted protein-hungry but not protein-fed females; and the odour of the fruit itself attracted mature females (especially experienced ones) but not immature females.

Association study of the dystrobrevin-binding gene with schizophrenia in Australian and Indian samples

Numerous studies have reported association between variants in the dystrobrevin binding protein 1 (dysbindin) gene (DTNBP1) and schizophrenia. However, the pattern of results is complex and to date, no specific risk marker or haplotype has been consistently identified. The number of single nucleotide polymorphisms (SNPs) tested in these studies has ranged from 5 to 20. We attempted to replicate previous findings by testing 16 SNPs in samples of 41 Australian pedigrees, 194 Australian cases and 180 controls, and 197 Indian pedigrees. No globally significant evidence for association was observed in any sample, despite power calculations indicating sufficient power to replicate several previous findings. Possible explanations for our results include sample differences in background linkage disequilibrium and/or risk allele effect size, the presence of multiple risk alleles upon different haplotypes, or the presence of a single risk allele upon multiple haplotypes. Some previous associations may also represent false positives. Examination of Caucasian HapMap phase II genotype data spanning the DTNBP1 region indicates upwards of 40 SNPs are required to satisfactorily assess all nonredundant variation within DTNBP1 and its potential regulatory regions for association with schizophrenia. More comprehensive studies in multiple samples will be required to determine whether specific DTNBP1 variants function as risk factors for schizophrenia.

Multi-species sequence comparison reveals conservation of ghrelin gene-derived splice variants encoding a truncated ghrelin peptide

The peptide hormone ghrelin is a potent orexigen produced predominantly in the stomach. It has a number of other biological actions, including roles in appetite stimulation, energy balance, the stimulation of growth hormone release and the regulation of cell proliferation. Recently, several ghrelin gene splice variants have been described. Here, we attempted to identify conserved alternative splicing of the ghrelin gene by cross-species sequence comparisons. We identified a novel human exon 2-deleted variant and provide preliminary evidence that this splice variant and in1-ghrelin encode a C-terminally truncated form of the ghrelin peptide, termed minighrelin. These variants are expressed in humans and mice, demonstrating conservation of alternative splicing spanning 90 million years. Minighrelin appears to have similar actions to full-length ghrelin, as treatment with exogenous minighrelin peptide stimulates appetite and feeding in mice. Forced expression of the exon 2-deleted preproghrelin variant mirrors the effect of the canonical preproghrelin, stimulating cell proliferation and migration in the PC3 prostate cancer cell line. This is the first study to characterise an exon 2-deleted preproghrelin variant and to demonstrate sequence conservation of ghrelin gene-derived splice variants that encode a truncated ghrelin peptide. This adds further impetus for studies into the alternative splicing of the ghrelin gene and the function of novel ghrelin peptides in vertebrates.