Analysis of Systemic Inflammatory Factors and Survival Outcomes in Endometrial Cancer Patients Staged I-III FIGO and treated with Postoperative External Radiotherapy

Background: The causal link between elevated systemic inflammation biomarkers and poor survival has been demonstrated in cancer patients. However, the evidence for this correlation in endometrial cancer (EC) is too weak to influence current criteria of risk assessment. Here, we examined the role of inflammatory indicators as a tool to identify EC patients at higher risk of death in a retrospective observational study. Methods: A total of 155 patients surgically diagnosed with EC stage I-III FIGO 2009 and treated with postoperative External Beam Radiotherapy (EBRT) brachytherapy and chemotherapy according to ESMO-ESTRO-ESGO recommendation for patients at high risk of recurrence at the Gustave Roussy Institut, France, and Hospital Clínic, Spain, between 2008 and 2017 were evaluated. The impact of pre-treatment Neutrophil-to-Lymphocyte Ratio (NLR 2.2), Monocyte-to-Lymphocyte Ratio (MLR 0.18), Systemic Immune-Inflammatory Index (SII 1100) and lymphopenia (<1.0 109/L) on overall survival (OS), cancer-specific survival and progression-free survival was evaluated. Subsequently, a cohort of 142 patients within high-advanced risk groups according to ESMO-ESGO-ESTRO classification was evaluated. Results: On univariate analysis, NLR (HR = 2.2, IC 95% 1.1-4.7), SII (HR = 2.2, IC 95% 1.1-4.6), MLR (HR = 5.0, IC 95% 1.1-20.8) and lymphopenia (HR = 3.8, IC 95% 1.6-9.0) were associated with decreased OS. On multivariate analysis, NLR, MLR, SII and lymphopenia proved to be independent unfavorable prognostic factors. Conclusions: lymphopenia and lymphocytes-related ratio are associated with poorer outcome in surgically staged I-III FIGO EC patients classified as high risk and treated with adjuvant EBRT and could be considered at cancer diagnosis. External validation in an independent cohort is required before implementation for patients' stratification

Poly(ADP-Ribose) Polymerase 1 (PARP-1) Regulates Ribosomal Biogenesis in Drosophila Nucleoli

Poly(ADP-ribose) polymerase 1 (PARP1), a nuclear protein, utilizes NAD to synthesize poly(AD-Pribose) (pADPr), resulting in both automodification and the modification of acceptor proteins. Substantial amounts of PARP1 and pADPr (up to 50%) are localized to the nucleolus, a subnuclear organelle known as a region for ribosome biogenesis and maturation. At present, the functional significance of PARP1 protein inside the nucleolus remains unclear. Using PARP1 mutants, we investigated the function of PARP1, pADPr, and PARP1-interacting proteins in the maintenance of nucleolus structure and functions. Our analysis shows that disruption of PARP1 enzymatic activity caused nucleolar disintegration and aberrant localization of nucleolar-specific proteins. Additionally, PARP1 mutants have increased accumulation of rRNA intermediates and a decrease in ribosome levels. Together, our data suggests that PARP1 enzymatic activity is required for targeting nucleolar proteins to the proximity of precursor rRNA; hence, PARP1 controls precursor rRNA processing, post-transcriptional modification, and pre-ribosome assembly. Based on these findings, we propose a model that explains how PARP1 activity impacts nucleolar functions and, consequently, ribosomal biogenesis

Magnetic resonance spectroscopy and imaging as applied to the forestry sector : a thesis submitted to Massey University in partial fulfilment for the degree of Doctor of Philosophy

The forestry sector in New Zealand ranks as the third largest export earner. The individual industries within the forestry sector have, in some cases, grown up on the basis of institutionalised knowledge, sometimes without a full understanding of the underlying fundamental physico-chemical relationships and the changes that occur during wood material processing. At the same time the commercial pressures of operating within the forestry sector have resulted in demand for more uniform, high quality, fit-for-purpose product, faster throughput and less downgrade from what is becoming a lower quality feedstock as harvest ages decline. In the 21st century, the forestry sector is being transformed into an "engineered ligno-cellulosic materials processor" and this in turn is requiring a more sophisticated knowledge of the material feedstock and the processes involved in wood products manufacture. The aim of this work was to use magnetic resonance techniques to explore aspects of ligno-cellulosic materials processing at points along the value-added process chain, namely drying, chemical modification (preservation) and re-engineering (gluing) of wood products. Magnetic resonance mini-imaging studies of the water transport during the drying of radiata pine boards rave shown differences in the directional movement of water within the wood structure. These effects show a dependence on the surface area to volume ratio of timber and the orientation of the annual rings with respect to the larger drying face. Narrow, flat-sawn boards exhibit anomalous drying behaviour in terms of water mass transport, whereas thicker boards display more conventional core-shell drying behaviour. These restrictions to flow have been further investigated using diffusion tensor imaging via a modified pulsed field gradient spin-echo sequence to elucidate the nature of anisotropic diffusion in wood. The direction of least restriction to self-diffusion is in the longitudinal direction, as would be expected with it being the direction of active transport within a tree stem, whereas the direction of greatest restriction to self-diffusion is in the radial direction, with the higher density latewood acting as a barrier. Preservation of radiata pine sapwood with novel boron-based preservatives has been investigated using magnetic resonance imaging to determine the penetration and retention of the incipient compounds. An apparent anomaly in retention for trimethylborate-treated Pinus radiata sapwood was investigated by 11B MAS NMR spectroscopy of excised sections of latewood and earlywood, which showed hydrolytic decomposition of trimethyl borate to form boric acid. The rate of hydrolysis of trimethylborate was monitored by 11B MAS NMR spectroscopy and was shown to occur very rapidly in the latewood (within 24 hours), and over a longer time scale of several days in the earlywood. The resulting publication has reported some of the first published 11B MRI images. Magnetic resonance spectroscopy has provided (in conjunction with separate mass spectrometry studies) mechanistic evidence for the accelerated curing of phenol-resorcinol formaldehyde resols, using ammonia in combination with the conventional paraformaldehyde hardener - a process known as GreenWeldTM. Carbon-13 and nitrogen-15 NMR spectroscopy has shown evidence of both benzylamine and aniline type bridging structures formed during cure, compared to only methylene structures being formed under conventional curing conditions. Poly(vinyl acetate) emulsion polymer adhesive has also been examined using NMR spectroscopic methods, with particular focus on the effect of addition of aluminium chloride, which is often commercially added to PVAc formulations as a crosslinking agent. Multinuclear magnetic resonance spectra obtained during the cure of AlCl3 modified PV Ac adhesive, shows a low frequency 27 Al shift of ca. 3 ppm suggesting a local change in environment as the aluminium changes from a solvated to a covalently bonded octahedral environment. Finally, as a preliminary study, a new device for measuring uniaxial extension of visco-elastic solids was trialled on poly(vinyl acetate) hydrogels to study the effect of addition of aluminium chloride on the visco-elastic properties of the adhesive. A similar, manually operated device was used to obtain NMR spectroscopic data during compression of the gel. These studies have shown that addition of aluminium chloride as a crosslinking agent, in fact produces a cured adhesive with fewer crosslinks than the corresponding unmodified adhesive, but with increased resistance to shear-induced creep

Diffuse reflectance near infrared spectroscopy can distinguish normal from enzymatically digested cartilage

A non-destructive, diffuse reflectance near infrared spectroscopy (DR-NIRS)approach is considered as a potential tool for determining the component-level structural properties of articular cartilage. To this end, DR-NIRS was applied in vitro to detect structural changes, using principal component analysis as the statistical basis for characterization. The results show that this technique, particularly with first-derivative pretreatment, can distinguish normal, intact cartilage from enzymatically digested cartilage. Further, this paper establishes that the use of DR-NIRS enables the probing of the full depth of the uncalcified cartilage matrix, potentially allowing the assessment of degenerative changes in joint tissue, independent of the site of initiation of the osteoarthritic process

Genetic variation of natural durability traits in Eucalyptus cladocalyx (sugar gum)

INTRODUCTION: We present a study on genetic variation in natural durability traits of young-aged Eucalyptus cladocalyx, a species adapted to temperate, low rainfall regions. Our motivation was the production of naturally durable posts for applications such as vine trellises, a sector dominated by heavy metal preservative-treated wood in some of the world’s main wine-producing countries. METHODS: Stem diameter at breast height over- and under-bark, heartwood proportion, wood density, methanol extractives and fungal decay were assessed in a progeny test on a set of 48 families from eight provenances nested within three regions of provenance (ROP) from the species’ natural range. Near-infrared reflectance (NIR) was examined as an efficient assessment method. RESULTS: Strong variation among ROP was indicated for all traits, with low-moderate narrow-sense heritability for growth traits and extractives content and moderate-high heritability of basic density and decay resistance to two of the three fungi. Trait–trait correlations ranged from low to high, with basic density and extractives content being negatively correlated to decay mass loss. DISCUSSION: NIR was an effective predictor of methanol extractives, moderately effective for basic density, but unsuccessful for fungal decay. Generally, there were no practically adverse correlations between growth and durability traits. CONCLUSION: Substantial genetic variation in natural durability traits is indicated, with wide scope for genetic improvement.The study was jointly funded by Rural Industries Research and Development Corporation and CSIRO

Near infrared spectral assessment of stay-green barley genotypes under heat stress

This research aimed to correlate near infrared (NIR) spectral data to physiological and biochemical responses associated with stay-green (SG) traits expression in barley (Hordeum vulgare L.) plants experiencing heat stress. One hundred lines were randomly sub-sampledfrom a doubled haploid ND24260 ~ Flagship population consisting of 334 lines. A glasshouse trial with partial sample duplicationwas grown under terminal heat stress to induce SG expression during grain-fill. The ggreennessh of the first leaves under the flag leaf (FL.1) was assessed using NIR spectra. A handheld NIR spectrometer was used to understand and describe some of the physiological and biochemical mechanisms and responses related to SG expression and vice versa which cannot be observed using visual assessments. The use of NIR spectroscopy made it possible both to differentiate between cosmetic (changes in pigments with senescence of spike but no functional chlorophyll affects) and functional (effects on chlorophyll catabolism) SG expression and also to differentiate between the two groups of functional SG. The delayed onset and reduced rate of leaf senescence was linked to plant moisture (water) and plant maturity, which is dependent on the level of SG expression. Variance in the dominant water peak at 1450 nm in the NIR spectrum can be used to differentiate between cosmetic and functional SG expression. The spectral data from the leaves showed significant correlation, with protein (R2 = 0.62) and starch (R2 = 0.70) composition of the grain. The use of NIR spectroscopy allows for the rapid, non-destructive analysis of leaves; enabling multiple traits to be assessed with a single measurement. Understanding the relationship between spectra and SG expression may help develop NIR spectroscopy as a rapid, high-throughput methodology for phenotyping breeding populations, with a view to improve drought resistant barley cultivars

Quantitative dynamics of stem water soluble carbohydrates in wheat can be monitored in the field using hyperspectral reflectance

The capacity of wheat to store water soluble carbohydrates (WSC) in the stem is regarded as a promising trait to buffer yield in environments with limited water availability. A high throughput, field-applicable, phenotyping technique would not only benefit agronomy/physiology applications but also help its quantification in wheat breeding programmes. The aim of this study was to evaluate if it was possible to estimate the concentration (WSCc, mgg-1) and amount (WSCa, gm-2) of stem WSC non-destructively and in situ using hyperspectral data obtained in wheat canopies, as opposed to currently available labour intensive laboratory methods. Hyperspectral reflectance data were obtained proximally at varying developmental stages from the canopy of wheat trials with a limited number of related genotypes growing under a range of management treatments, in two successive years. Data were calibrated, firstly independently for each year and then jointly, to provide a measure of stem WSC using partial least squares regression on wavelengths in the range of 350-1290nm. Pre-treated spectra (second derivative) enabled calibrations for the combined years with concentration (WSCc, mgg-1) (r2=0.90) and amount (WSCa, gm-2) (r2=0.88) of water soluble carbohydrate in the stems. In addition, from the same measurement, other canopy properties, leaf area index and canopy water content, could be simultaneously predicted. This study has shown that calibration models from canopy level data can robustly predict the dynamics of stem WSC throughout crop stages and treatments, while at the same time including variation in indices diagnostic of crop water and cover status, such as the Water Index and Enhanced Vegetation Index. Promising WSC prediction using spectral data below 1000nm needs to be investigated further, in order to harness the potential for impact using low cost silicon detectors