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The degeneration and death of motor neurons lead to motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Although the exact mechanism by which motor neuron degeneration occurs is not well understood, emerging evidence implicates the involvement of ferroptosis, an iron-dependent oxidative mode of cell death. We reported previously that treating Gpx4NIKO mice with tamoxifen to ablate the ferroptosis regulator glutathione peroxidase 4 (GPX4) in neurons produces a severe paralytic model resembling an accelerated form of ALS that appears to be caused by ferroptotic cell death of spinal motor neurons. In this study, in support of the role of ferroptosis in this model, we found that the paralytic symptoms and spinal motor neuron death of Gpx4NIKO mice were attenuated by a chemical inhibitor of ferroptosis. In addition, we observed that the paralytic symptoms of Gpx4NIKO mice were malleable and could be tapered by lowering the dose of tamoxifen, allowing for the generation of a mild paralytic model without a rapid onset of death. We further used both models to evaluate mitochondrial reactive oxygen species (mtROS) in the ferroptosis of spinal motor neurons and showed that overexpression of peroxiredoxin 3, a mitochondrial antioxidant defense enzyme, ameliorated symptoms of the mild but not the severe model of the Gpx4NIKO mice. Our results thus indicate that the Gpx4NIKO mouse is a versatile model for testing interventions that target ferroptotic death of spinal motor neurons in vivo. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) often experience chronic pelvic and even systemic pain that can be difficult to clinically manage. Pulsed electromagnetic field (PEMF) therapy, a non-invasive strategy that has shown significant efficacy for pain reduction in other chronic pain conditions, may provide benefit for pain management in patients with IC/BPS. Methods: PEMF delivery to patients occurs via a bio-electromagnetic-energy device which consists of a flexible mat (180 × 50 cm) that the patient lies on for systemic, full-body delivery and/or a flexible pad (50 × 15 cm) for targeted delivery to a specific body region (e.g., pelvic area). The duration of individual sessions, number of sessions per day, total number of sessions, and follow-up observation period vary between previously published studies. Positive outcomes are typically reported as a significant reduction in visual analog scale (VAS) pain score and functional improvement assessed using validated questionnaires specific to the condition under study. Results and conclusions: The use of PEMF has been evaluated as a therapeutic strategy for pain management in several clinical scenarios. Randomized, double-blinded, placebo-controlled trials have reported positive efficacy and safety profiles when PEMF was used to treat non-specific low back pain, patellofemoral pain syndrome, chronic post-operative pain, osteoarthritis-related pain, rheumatoid arthritis-related pain, and fibromyalgia-related pain. Based on these positive outcomes in a variety of pain conditions, clinical trials to evaluate whether PEMF can provide a safe, non-invasive therapeutic approach to improve symptoms of chronic pain and fatigue in patients with IC/BPS are warranted. [ABSTRACT FROM AUTHOR]

The application of cutting fluids to the machining of titanium alloys has received increasing interest due to the severe tribological conditions occurring during this process. Cutting fluids are applied during the machining process to reduce tool wear, friction, and heat generation. This study was carried out to investigate the effect of polymer-based additives and phosphorus-based additives on the cutting fluid performance during the drilling of a titanium alloy, Ti-6Al-4V, under a constant metal removal rate (MRR) of 4.2 mm3/s. The tool wear and specific cutting energy (SCE) were evaluated to assess the performance of the additives in a cutting fluid. The performance of the additives was dependent on the drilling conditions. At the lower limit of the drilling conditions tested (500 RPM under 4.2 mm3/s MRR), the cutting fluid with high phosphorus concentration was able to achieve better lubricity. While at the higher limit drilling conditions (700–2500 RPM under 4.2 mm3/s MRR), the cutting fluid with primarily polymer-based additives was more effective at providing improved drilling performance. The improvement in the drilling performance of the cutting fluids was related to the formation of boundary layers associated with additives employed. An optimum range (providing the lowest SCE value) within the tested drilling conditions was noted for the cutting fluids. [ABSTRACT FROM AUTHOR]

Vial-based lyophilization for biopharmaceuticals has been an indispensable cornerstone process for over 50 years. However, the process is not without significant challenges. Capital costs to realize a lyophilized drug product facility, for example, are very high. Similarly, heat and mass transfer limitations inherent in lyophilization result in drying cycle on the order of several days while putting practical constraints on available formulation space, such as solute mass percentage or fill volume in a vial. Through collaboration with an external partner, we are exploring microwave vacuum drying (MVD) as a faster drying process to vial lyophilization wherein the heat transfer process occurs by microwave radiation instead of pure conduction from the vial. Drying using this radiative process demonstrates greater than 80% reduction in drying time over traditional freeze-drying times while maintaining product activity and stability. Such reduction in freeze-drying process times from days to several hours is a welcome change as it enables flexible manufacturing by being able to better react to changes either in terms of product volume for on-demand manufacturing scenarios or facilities for production (e.g., scale-out over scale-up). Additionally, by utilizing first-principle modeling coupled with experimental verification, a mechanism for faster drying times associated with MVD is proposed in this article. This research, to the best of our knowledge, forms the very first report of utilizing microwave vacuum drying for vaccines while utilizing the power of simplified models to understand drying principles associated with MVD. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Low anesthetic bladder capacity has been shown to be a biomarker for bladder-centric interstitial cystitis/bladder pain syndrome (IC/BPS). The goal of this study was to determine if histopathological evidence from bladder biopsies supports anesthetic bladder capacity (BC) as a marker to distinguish a bladder-centric IC/BPS subtype. Methods: From a review of our large IC/BPS cohort of patients undergoing hydrodistention, we identified a total of 41 patients with low BC (≤ 400 ml); an additional 41 consecutive patients with BC > 400 ml were selected as the comparator group. The original bladder mucosal biopsy pathology slides were re-reviewed by a single pathologist (blinded to patient information) using a standardized grading scale developed for this study. Results: Histologically, the low BC subjects exhibited higher levels of acute inflammation (p = 0.0299), chronic inflammation (p = 0.0139), and erosion on microscopy (p = 0.0155); however, there was no significant difference in mast cell count between groups (p = 0.4431). There was no significant gender difference between the groups; female patients were the majority in both groups (low BC: 94.12%, non-low BC: 100%; p = 0.1246). Individuals in the low BC group were older (p < 0.0001), had a higher incidence of Hunner's lesions on cystoscopy (p < 0.0001), and had significantly higher scores, i.e., more bother symptoms, on two IC/BPS questionnaires (ICPI, p = 0.0154; ICSI, p = 0.0005). Conclusions: IC/BPS patients with low anesthetic bladder capacity have histological evidence of significantly more acute and chronic inflammation compared with patients with a non-low bladder capacity. These data provide additional evidence to support low bladder capacity as a marker of a distinct bladder-centric IC/BPS phenotype. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Interstitial cystitis/bladder pain syndrome (IC/BPS) and fibromyalgia (FM) are frequently co-occurring medical diagnoses in patients referred to the urology clinic for secondary and tertiary treatment options. Methods: Abundant literature has shown that many patients with FM have small fiber polyneuropathy (SFPN) that can be confirmed via skin punch biopsy and immunological staining to measure nerve density. Results and conclusions: This finding of SFPN provides a therapeutic target for FM and in this article we hypothesize and provide rationale for the idea that this same phenomenon (SFPN) might explain, in some IC/BPS patients, the finding of widespread pain and likewise provide a therapeutic target for these patients. [ABSTRACT FROM AUTHOR]

Companies are increasing their use of cause-related marketing as a means of communicating their commitment to corporate social responsibility while accomplishing their strategic goals. Although prior studies suggest that consumers react positively to cause-related marketing programs, understanding of their impact on financial performance remains limited. To address this gap, the authors employ an event study to examine the effects of cause-related marketing announcements on shareholder value using a sample of firms that appeared on Fortune's Most Admired All-Star list between 2005 and 2017. Study results show that announcement of these initiatives results in a significant loss of shareholder value. These losses are most pronounced for firms making monetary-only contributions, in comparison to those that make in-kind donations. In addition, the negative effects are mitigated for firms that have stronger reputations, have greater resource slack, and operate in more dynamic industries. Moreover, low-reputation and low-slack firms benefit most from in-kind contributions. [ABSTRACT FROM AUTHOR]

Although guidelines are available for hereditary hemochromatosis, a high percentage of the recommendations within them are not shared between the different guidelines. Our main aim is to provide an objective, simple, brief, and practical set of recommendations about therapeutic aspects of HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype, based on the published scientific studies and guidelines, in a form that is reasonably comprehensible to patients and people without medical training. This final version was approved at the Hemochromatosis International meeting on 12th May 2017 in Los Angeles. [ABSTRACT FROM AUTHOR]

Individual athletes, coaches and sports teams seek continuously for ways to improve performance and accomplishment in elite competition. New techniques of performance analysis are a crucial part of the drive for athletic perfection. This paper discusses the ethical importance of one aspect of the future potential of performance analysis in sport, combining the field of biomedicine, sports engineering and nanotechnology in the form of 'Nanobiosensors'. This innovative technology has the potential to revolutionise sport, enabling real time biological data to be collected from athletes that can be electronically distributed. Enabling precise real time performance analysis is not without ethical problems. Arguments concerning (1) data ownership and privacy; (2) data confidentiality; and (3) athlete welfare are presented alongside a discussion of the use of the Precautionary Principle in making ethical evaluations. We conclude, that although the future potential use of Nanobiosensors in sports analysis offers many potential benefits, there is also a fear that it could be abused at a sporting system level. Hence, it is essential for sporting bodies to consider the development of a robust ethically informed governance framework in advance of their proliferated use. [ABSTRACT FROM AUTHOR]

PqqB is an enzyme involved in the biosynthesis of pyrroloquinoline quinone and a distal member of the metallo-β-lactamase (MBL) superfamily. PqqB lacks two residues in the conserved signature motif HxHxDH that makes up the key metal-chelating elements that can bind up to two metal ions at the active site of MBLs and other members of its superfamily. Here, we report crystal structures of PqqB bound to Mn, Mg, Cu, and Zn. These structures demonstrate that PqqB can still bind metal ions at the canonical MBL active site. The fact that PqqB can adapt its side chains to chelate a wide spectrum of metal ions with different coordination features on a uniform main chain scaffold demonstrates its metal-binding plasticity. This plasticity may provide insights into the structural basis of promiscuous activities found in ensembles of metal complexes within this superfamily. Furthermore, PqqB belongs to a small subclass of MBLs that contain an additional CxCxxC motif that binds a structural Zn. Our data support a key role for this motif in dimerization. [ABSTRACT FROM AUTHOR]

The ribosomally synthesized and post-translationally modified peptide (RiPP), pyrroloquinoline quinone (PQQ), is a dehydrogenase cofactor synthesized by, but not exclusively used by, certain prokaryotes. RiPPs represent a rapidly expanding and diverse class of natural products-many of which have therapeutic potential-and the biosynthetic pathways for these are gaining attention. Five gene products from the pqq operon (PqqA, PqqB, PqqC, PqqD, and PqqE) are essential for PQQ biosynthesis. The substrate is the peptide PqqA, which is presented to the radical SAM enzyme PqqE by the small protein PqqD. PqqA is unstructured in solution, and only binds to PqqE when in complex with PqqD. PqqD is a member of a growing family of RiPP chaperone proteins (or domains in most cases) that present their associated peptide substrates to the initial RiPP biosynthesis enzymes. An X-ray crystal structure exists for dimeric Xanthomonas campestris PqqD (PDB ID: 3G2B), but PqqD is now known to act as a monomer under physiological conditions. In this study, the PqqD truncation from naturally fused Methylobacterium extorquens ( Mex) PqqCD was overexpressed in Escherichia coli and MexPqqA was chemically synthesized. Solution NMR H-,N-HSQC chemical shift studies have identified the PqqD residues involved in binding PqqA, and H, C, and N peak assignments for PqqD alone and for PqqD bound to PqqA are reported herein. [ABSTRACT FROM AUTHOR]

Interstitial cystitis/bladder pain syndrome is a complex urologic disorder often managed in a non-operative fashion, but patients with severe symptoms occasionally require surgical intervention. Several approaches to reconstruction have been reported, including trigone-sparing cystectomy with enterocystoplasty, simple cystectomy with diversion, and diversion without cystectomy. While a trigone-sparing approach offers the potential for spontaneous voiding, it leaves bladder and urethral tissue that can cause pain postoperatively. Final choice of surgery is based upon surgeon and patient preference. In recent years, enhanced recovery after surgery (ERAS) protocols modeled after colorectal surgery have been utilized for radical cystectomy postoperative management with success. These approaches can be used for cystectomy for non-malignant cases as well. [ABSTRACT FROM AUTHOR]

Little attention was given to the climatic signals in wood properties, such as microfibril angle (MFA) and tracheid radial diameter (TRD). In this article, year-to-year variation in MFA and TRD was measured by SilviScan-3 on dated Picea crassifolia trees growing at three altitudes in the northeastern Tibetan plateau. Climatic signals registered in MFA and TRD were analyzed using dendroclimatology methods. The annual variation of MFA and TRD was strongly linked to high-frequency climatic signals. Both MFA and TRD were negatively correlated with temperature and positively correlated with precipitation. The temperature had a similar influence on MFA and TRD at three different altitudes, while the influence of precipitation decreased with the increasing altitudes. MFA was negatively correlated with TRD, and this MFA-TRD internal relationship ( R) varied with calendar year. Temperature and precipitation had a strong influence on R. Temperature was positively correlated with R, and precipitation was negatively correlated with R. The influence of temperature was stronger than that of precipitation. The influence of temperature increased with the increase in altitudes, while the influence of precipitation decreased with the increasing altitudes. Results of this study revealed that the trees could change their internal characteristics to adapt to the changing climate. [ABSTRACT FROM AUTHOR]

In this work, antitumor compounds, lactoferrin [recombinant iron-free (Apo-rLf)], cisplatin (Cis) or their combination were embedded within a biodegradable polycaprolactone (PCL) polymer thin film, by a modified approach of a laser-based technique, matrix-assisted pulsed laser evaporation (MAPLE). The structural and morphological properties of the deposited hybrid films were analyzed by Fourier-transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). The in vitro effect on the cells' morphology and proliferation of murine melanoma B16-F10 cells was investigated and correlated with the films' surface chemistry and topography. Biological assays revealed decreased viability and proliferation, lower adherence, and morphological modifications in the case of melanoma cells cultured on both Apo-rLf and Cis thin films. The antitumor effect was enhanced by deposition of Apo-rLf with Cis within the same film. The unique capability of the new approach, based on MAPLE, to embed antitumor active factors within a biodegradable matrix for obtaining novel biodegradable hybrid platform with increased antitumor efficiency has been demonstrated. [ABSTRACT FROM AUTHOR]

Bladder instillation therapy refers to the direct introduction of medication into the bladder and is a common treatment modality for patients with interstitial cystitis/bladder pain syndrome (IC/BPS) who have failed conservative and oral therapies. The current American Urological Association (AUA) recommendations list three medications as options for IC/BPS instillation therapy: dimethyl sulfoxide, heparin, and lidocaine. The purpose of this review is to examine the evidence behind the recommendations for these medications. We also examine several historical or experimental therapies that do not hold recommendations but are still used on rare occasion. Finally, we discuss our bladder instillation strategies as well as potential future research and development in intravesicular therapy. [ABSTRACT FROM AUTHOR]

More than 20 years of private and public research on site-specific variable rate sprinkler irrigation (SS-VRI) technology on self-propelled center pivot and linear move irrigation systems has resulted in limited commercial adoption of the technology. Competing patents, liability, and proprietary software have affected industry's willingness to move into a new technology area. Documented and proven water conservation strategies using site-specific irrigation are quite limited. Marginal costs associated with site-specific technologies are high. Although sales of SS-VRI are increasing, they are primarily being used for eliminating irrigation and chemigation on non-cropped areas of a field or for land application of liquid agricultural and municipal wastes. Various aspects of SS-VRI technologies for general crop production are beginning to slowly gain widespread acceptance; however, their uses are largely focused on addressing symptoms of poor design and sub-optimal water and nutrient management. Although currently underutilized, SS-VRI technology has the potential to positively impact crop water productivity, water and energy conservation, and the environment. There are also few economic incentives to motivate growers to move to higher levels of SS-VRI management. Greater adoption rates will likely require higher costs for water and energy, severely restricted water diversions on a broad scale, and enforcement of compliance with environmental and other regulations. Sustainable use of SS-VRI will require strong research support, which is currently limited. In the short term, adoption of SS-VRI technologies will be enhanced by addressing equipment deficiencies and research developing basic criteria and systems for defining management zones and locations of various sensor systems for both arid and humid regions. Training adequate personnel to help write site-specific variable rate irrigation prescriptions in humid and arid areas to assist growers with the decision-making process is also a high priority. There is also a large need to educate government boards and bankers on the potential benefits of these systems. The long-term challenges will be to demonstrate that SS-VRI will improve water management or increase net returns. There is a critical need to develop fully integrated management systems with supporting elements that accurately and inexpensively define dynamic management zones, sense within-field variability in real time, and then adaptively control site-specific variable rate water applications, which will be challenging as significant knowledge gaps exist. [ABSTRACT FROM AUTHOR]

A radial core from a Norway spruce ( Picea abies (L.) Karst.) estimated to be about 107 years old was cut from a board and was analyzed for density and microfibril angle (MFA). Furthermore, cell geometry, wall thickness and lignin distribution were analyzed on three selected growth rings in detail. Intra-ring differences in the density profiles are also true for cell wall thicknesses as well as radial and tangential lumen diameters. A higher MFA was found for earlywood with a slow decrease toward the latewood region. The lignin was found to remain rather constant throughout the growth rings, which suggests a constant chemical composition of the cell wall material within the growth ring. From the recorded datasets on a cellular level, it can be concluded that the main adaptation regarding structure-property relationships toward the optimization of water transport and mechanical stability is mainly achieved at the cell level. [ABSTRACT FROM AUTHOR]

This study presents three-point bending test results of Norway spruce clear wood specimens loaded on the radial-longitudinal plane in two different load cases. The tested samples were graded as resonance wood for instrument making and were characterised by narrow annual rings and relatively low density. The modulus of elasticity (MOE) and the corresponding modulus of rupture (MOR) are illustrated separately for the samples with straight grain and the group showing the specific growth pattern of indented rings ('hazel growth'). With the longitudinal wood anatomical direction parallel to span width, the fibre deviation caused by the indents reduces MOE and MOR values, whereas a 'reinforcing' effect of the indents could be observed for the load case with span width parallel to the radial direction. Both aspects lead to a reduction in anisotropy for hazel-growth Norway spruce (anisotropy MOE: indented rings 11.6, straight grain 14.7, anisotropy MOR: indented rings 6.9, straight grain 8.9), which partly explains the exceptional position of this growth pattern for the construction of high-class musical instruments with outstanding mechanical and acoustical performance. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to document the early and late complications associated with frontofacial distraction. Method: A systematic review of the literature on complications in craniofacial surgery and a review of records of patients undergoing frontofacial distraction at Great Ormond Street Hospital for Children over a 10-year period were conducted. Results: Complications arising from frontofacial advancement are common. Mortality rates varied between 0 and 4.5 %. There has been a general decline in reported mortality rates with time, and the most recent series report mortalities of less than 1 %. The incidence of significant blood loss (greater than one blood volume) in patients undergoing monobloc osteotomy varied between 5.3 and 9.1 %. CSF leaks following monobloc distraction are common (incidence, 2-20 %). Most of these leaks settle spontaneously. The incidence of frontal bone flap necrosis requiring debridement and a subsequent cranioplasty varied between 3 and 20 %. Conclusions: The functional and aesthetic benefits of frontofacial distraction are well documented, but these advantages are associated with a significant complication rate. The potential benefits of frontofacial distraction need to be carefully weighed against the potential complications when deciding to recommend surgery. [ABSTRACT FROM AUTHOR]

Provenance variation and genetic parameters for wood properties of mature radiata pine ( Pinus radiata D. Don) were studied by sampling three provenance/progeny trials in southeast Australia. Among the mainland provenances, Monterey and Año Nuevo had higher density and modulus of elasticity (at one site) than Cambria. Basic density and predicted modulus of elasticity (MoE) for the island provenances, Guadalupe and Cedros, were ∼20% higher at Billapaloola compared to mainland provenances grown at Green Hills and Salicki, differences that may or may not be linked to site differences. Heritability estimates of density, predicted MoE and microfibril angle were significant and $$ {\bar{h}^2} $$ > 0.45, suggesting moderate to strong genetic control. The estimated genetic correlations between diameter at breast height and wood properties in the current study were weaker (less negative) than the mean estimated from the current breeding population generation in radiata pine. Of the wood properties, density showed the strongest adverse genetic correlations with growth (mean r = −0.23 ± 0.09). Selection for MoE may produce greater gain than selection for density because MoE had almost twice the estimated additive genetic coefficient of variation ( $$ {\overline {\text{CV}}_A} $$) compared to density. Estimated type B genetic correlations ( r) for all wood quality traits were typically high, conforming to the trend that wood properties have low genotype-by-environment interaction (G × E). Significant differences in wood properties among provenances, families and/or individual trees provide an opportunity for breeding programmes to select superior trees for solid wood production that will combine superior growth with desirable wood traits. [ABSTRACT FROM AUTHOR]

Management practices may influence dryland soil N cycling. We evaluated the effects of tillage, crop rotation, and cultural practice on dryland crop biomass (stems and leaves) N, surface residue N, and soil N fractions at the 0-20 cm depth in a Williams loam from 2004 to 2008 in eastern Montana, USA. Treatments were two tillage practices (no-tillage [NT] and conventional tillage [CT]), two crop rotations (continuous spring wheat [ Triticum aestivum L.] [CW] and spring wheat-barley [ Hordeum vulgaris L.] hay-corn [ Zea mays L.]-pea [ Pisum sativum L.] [W-B-C-P]), and two cultural practices (regular [conventional seed rates and plant spacing, conventional planting date, broadcast N fertilization, and reduced stubble height] and ecological [variable seed rates and plant spacing, delayed planting, banded N fertilization, and increased stubble height]). Nitrogen fractions were soil total N (STN), particulate organic N (PON), microbial biomass N (MBN), potential N mineralization (PNM), NH-N, and NO-N. Crop biomass N was 30 % greater in W-B-C-P than in CW in 2005. Surface residue N was 30-34 % greater in NT with the regular and ecological practices than in CT with the regular practice. The STN, PON, and MBN at 10-20 and 0-20 cm were 5-41 % greater in NT or CW with the regular practice than in CT or CW with the ecological practice. The PNM at 5-10 cm was 22 % greater in the regular than in the ecological practice. The NH-N and NO-N contents at 10-20 and 0-20 cm were greater in CT with W-B-C-P and the regular practice than with most other treatments in 2007. Surface residue and soil N fractions, except PNM and NO-N, declined from autumn 2007 to spring 2008. In 2008, NT with W-B-C-P and the regular practice gained 400 kg N ha compared with a loss of 221 kg N ha to a gain of 219 kg N ha in other treatments. No-tillage with the regular cultural practice increased surface residue and soil N storage but conventional tillage with diversified crop rotation and the regular practice increased soil N availability. Because of continuous N mineralization, surface residue and soil N storage decreased without influencing N availability from autumn to the following spring. [ABSTRACT FROM AUTHOR]

Microfibril angle (MFA) is an important factor in determining the mechanical properties of individual cells and wood as a whole. While some studies have described the variation of MFA within trees, little work has been done on the extent to which MFA is influenced by climate, despite it being known to respond to climatic events. Year-to-year variation in MFA and ring width was measured at high resolution by SilviScan-3 on 30 dated Picea crassifolia trees growing in the northeastern Tibetan plateau. The climate signals registered in MFA and ring width were analyzed using dendroclimatological methods. The response function of MFA accounted for 67% of total variance, of which 60% was explained by climate elements. The response function of ring width explained 57% total variance, 37% of which was explained by climate variables. MFA significantly responded to July-August temperatures, and to precipitation in March, May and September. Over the period 1987-2009 temperatures generally increase and appeared to have a greater influence on MFA. A decrease in the strength of the relationship between MFA and ring width over the period 1987-2009 was also observed. MFA offers the potential to build robust climate proxies. The strong climate sensitivity of MFA to increasing temperature or the observed changes in the MFA-ring width relationship may contribute to resolving the 'divergence problem' in temperature reconstructions. As far as we are aware, this study is the first to show a strong climate response in MFA and suggests that it might be a useful climate proxy. [ABSTRACT FROM AUTHOR]

Neisseria are obligate human pathogens causing bacterial meningitis, septicaemia and gonorrhoea. Neisseria require iron for survival and can extract it directly from human transferrin for transport across the outer membrane. The transport system consists of TbpA, an integral outer membrane protein, and TbpB, a co-receptor attached to the cell surface; both proteins are potentially important vaccine and therapeutic targets. Two key questions driving Neisseria research are how human transferrin is specifically targeted, and how the bacteria liberate iron from transferrin at neutral pH. To address these questions, we solved crystal structures of the TbpA-transferrin complex and of the corresponding co-receptor TbpB. We characterized the TbpB-transferrin complex by small-angle X-ray scattering and the TbpA-TbpB-transferrin complex by electron microscopy. Our studies provide a rational basis for the specificity of TbpA for human transferrin, show how TbpA promotes iron release from transferrin, and elucidate how TbpB facilitates this process. [ABSTRACT FROM AUTHOR]

Cambial growth and wood properties respond to fluctuating environmental conditions. Understanding the nature of these responses is crucial to understanding their cumulative effect on the wood quality characteristics of a forest stand. This paper reports on a study conducted over a period of 3½ years in continuously irrigated, alternately irrigated and non-irrigated Eucalyptus globulus, in which changes in wood density occurring in response to short-term growth responses were examined. The study showed that continuous irrigation led to the production of wood with significantly more homogenous density than was the case in situations, where trees experienced large fluctuations in temporal water availability. Although the trees which were not irrigated had the highest wood density overall, trees in which growth was relatively continuous tended to produce the largest volumes of wood with relatively high density, compared to trees in which periodic growth responses were caused by intermittent irrigation, in which wood density was actually reduced. This was largely due to more growth days in summer under the conditions of higher radiation, and a reduction in the number of growth events leading to the production of disproportionately large amounts of low density wood. Soil water deficits contributed to density variation in all treatments, but the effect of energy limitations became more important in continuously irrigated trees. [ABSTRACT FROM AUTHOR]

Novel management practices are needed to increase dryland soil organic matter and crop yields that have been declining due to long-term conventional tillage with spring wheat ( Triticum aestivum L.)-fallow system in the northern Great Plains, USA. The effects of tillage, crop rotation, and cultural practice were evaluated on dryland crop biomass (stems + leaves) yield, surface residue, and soil organic C (SOC) and total N (STN) at the 0-20 cm depth in a Williams loam (fine-loamy, mixed, superactive, frigid, Typic Argiustolls) from 2004 to 2007 in eastern Montana, USA. Treatments were two tillage practices [no-tillage (NT) and conventional tillage (CT)], four crop rotations [continuous spring wheat (CW), spring wheat-pea ( Pisum sativum L.) (W-P), spring wheat-barley ( Hordeum vulgaris L.) hay-pea (W-B-P), and spring wheat-barley hay-corn ( Zea mays L.)-pea (W-B-C-P)], and two cultural practices [regular (conventional seed rates and plant spacing, conventional planting date, broadcast N fertilization, and reduced stubble height) and ecological (variable seed rates and plant spacing, delayed planting, banded N fertilization, and increased stubble height)]. Crop biomass and N content were 4 to 44% greater in W-B-C-P than in CW in 2004 and 2005 and greater in ecological than in regular cultural practice in CT. Soil surface residue amount and C and N contents were greater in NT than in CT, greater in CW, W-P, and W-B-C-P than in W-B-P, and greater in 2006 and 2007 than in 2004 and 2005. The SOC and STN concentrations at 0-5 cm were 4 to 6% greater in CW than in W-P or W-B-P in NT and CT from 2005 and 2007. In 2007, SOC content at 10-20 cm was greater in W-P and W-B-P than in W-B-C-P in CT but STN was greater in W-B-P and W-B-C-P than in CW in NT. From 2004 to 2007, SOC and STN concentrations varied at 0-5 cm but increased at 5-20 cm. Diversified crop rotation and delayed planting with higher seed rates and banded N fertilization increased the amount of crop biomass returned to the soil and surface residue C and N. Although no-tillage increased surface residue C and N, continuous nonlegume cropping increased soil C and N levels at the surface layer compared with other crop rotations. Continued return of crop residue from 2004 to 2007 may increase soil C and N levels but long-term studies are needed to better evaluate the effect of management practices on soil C and N levels under dryland cropping systems in the northern Great Plains. [ABSTRACT FROM AUTHOR]

Overactive bladder associated with pain (ie, interstitial cystitis/bladder pain syndrome [IC/BPS]) is a prevalent condition that can be very difficult to diagnose and even more difficult to treat. In this paper, we review the studied therapies for IC/BPS, including non-medication-based therapies, oral and intravesical-based medications, and surgical treatments for interstitial cystitis. We also review an approach to the treatment of a patient with IC/BPS using the previously published UPOINT clinical phenotyping template. [ABSTRACT FROM AUTHOR]

We conducted an inverse modeling analysis, using a variety of data streams (tower-based eddy covariance measurements of net ecosystem exchange, NEE, of CO2, chamber-based measurements of soil respiration, and ancillary ecological measurements of leaf area index, litterfall, and woody biomass increment) to estimate parameters and initial carbon (C) stocks of a simple forest C-cycle model, DALEC, using Monte Carlo procedures. Our study site is the spruce-dominated Howland Forest AmeriFlux site, in central Maine, USA. Our analysis focuses on: (1) full characterization of data uncertainties, and treatment of these uncertainties in the parameter estimation; (2) evaluation of how combinations of different data streams influence posterior parameter distributions and model uncertainties; and (3) comparison of model performance (in terms of both predicted fluxes and pool dynamics) during a 4-year calibration period (1997–2000) and a 4-year validation period (“forward run”, 2001–2004). We find that woody biomass increment, and, to a lesser degree, soil respiration, measurements contribute to marked reductions in uncertainties in parameter estimates and model predictions as these provide orthogonal constraints to the tower NEE measurements. However, none of the data are effective at constraining fine root or soil C pool dynamics, suggesting that these should be targets for future measurement efforts. A key finding is that adding additional constraints not only reduces uncertainties (i.e., narrower confidence intervals) on model predictions, but at the same time also results in improved model predictions by greatly reducing bias associated with predictions during the forward run. [ABSTRACT FROM AUTHOR]

A number of studies have reported the anti-tumoral activity of lactoferrin, a property mediated by a variety of mechanisms such as inhibitory effects on tumor cell growth, NK cell activation, and enhancement of apoptosis. Liposomes are known to be an efficient drug delivery system which can enhance the therapeutic potential of the encapsulated compounds. We have used positively charged liposomes composed of phosphatidylcholine (PC), dioleoylphosphatidylethanolamine (DOPE), cholesterol (Chol) and stearylamine (SA) (6:1:2:1 M ratio) as a carrier system for bovine iron-free Lf (ApoBLf), and compared the in vitro effect of free and liposome-entrapped ApoBLf on the growth and morphology of murine melanoma B16-F10 cells. Liposomal formulation of ApoBLf was found to enhance the capacity of the protein to inhibit the cell proliferation by affecting cell cycle progression. The effect appeared to be due to the capacity of liposomes to increase the uptake of the protein and its accumulation into cells and probably to protect it from degradation, as revealed by fluorescence microscopy and flow cytometry . Our results demonstrate the ability of liposomes to improve the anti-tumor activity of Lf and suggest that liposomal protein may have a potential therapeutic use in the prevention and/or treatment of cancer diseases. [ABSTRACT FROM AUTHOR]

Continuous move irrigation systems such as linear move and center pivot irrigate unevenly when applying conventional uniform water rates due to the towers/motors stop/advance pattern. The effect of the gear drive/cart movement pattern on linear move water application is larger on the first two spans, which introduces errors on site-specific irrigation. Therefore, the objectives of this study were to model the linear move irrigation system cart movement and to develop an algorithm to compensate for unintended variable irrigation (application errors). The cart advance/movement modeling considered terrain attributes, average nozzle travel speed, and high frequency DGPS (differential global positioning system) cart positioning readings. This paper describes the use of an irrigation monitoring and control system, DGPS, GIS, and statistical analysis utilized in the modeling and compensation processes. The irrigation monitoring and control system was composed of a single board computer, a relay board controller, DGPS, electric solenoid valves, wireless ethernet bridge units, high frequency spread spectrum radios, as well as in-line and in-field sensor networks. This technology allowed for continuous, real-time data acquisition and irrigation system management through the internet. This study has shown that irrigation application errors were reduced from over 20% to around 5%, in the subsequent irrigation event. [ABSTRACT FROM AUTHOR]

Despite its importance in iron-overload diseases, little is known about the composition of plasma non-transferrin-bound iron (NTBI). Using 30-kDa ultrafiltration, plasma from thalassemic patients consisted of both filterable and non-filterable NTBI, the filterable fraction representing less than 10% NTBI. Low filterability could result from protein binding or NTBI species exceeding 30 kDa. The properties of iron citrate and its interaction with albumin were therefore investigated, as these represent likely NTBI species. Iron permeated 5- or 12-kDa ultrafiltration units completely when complexes were freshly prepared and citrate exceeded iron by tenfold, whereas with 30-kDa ultrafiltration units, permeation approached 100% at all molar ratios. A g = 4.3 electron paramagnetic resonance signal, characteristic of mononuclear iron, was detectable only with iron-to-citrate ratios above 1:100. The ability of both desferrioxamine and 1,2-dimethyl-3-hydroxypyridin-4-one to chelate iron in iron citrate complexes also increased with increasing ratios of citrate to iron. Incremental molar excesses of citrate thus favour the progressive appearance of chelatable lower molecular weight iron oligomers, dimers and ultimately monomers. Filtration of iron citrate in the presence of albumin showed substantial binding to albumin across a wide range of iron-to-citrate ratios and also increased accessibility of iron to chelators, reflecting a shift towards smaller oligomeric species. However, in vitro experiments using immunodepletion or absorption of albumin to Cibacron blue–Sepharose indicate that iron is only loosely bound in iron citrate–albumin complexes and that NTBI is unlikely to be albumin-bound to any significant extent in thalassemic sera. [ABSTRACT FROM AUTHOR]

The sediment–water interface is usually marked by an increase in acoustic impedance and is therefore displayed in a seismic section as a positive polarity reflection. Here, we use the term “seabed phase reversal” to describe areas of seafloor which are instead expressed as a negative polarity reflection in seismic data. We describe in detail a number of examples of seafloor phase reversals and use a simple one-dimensional geophysical model to test the hypothesis that they are the result of the presence of gas within the seafloor sediment. Our examples are all related to seismically imaged mud volcanoes located within the South Caspian Sea. Sections of phase-reversed seafloor at the summit area of these volcanoes have been mapped to reveal the existence of seafloor mud pools (salses) and recently erupted mud flows which show a strong similarity to smaller-scale features at onshore volcanoes in Azerbaijan. Synthetic geophysical modelling indicates that under the physical conditions likely to occur when the seabed sediment is gas-bearing, the seafloor will be expressed as a strong negative polarity reflection. Unlike other indicators of seafloor gas, such as pockmarks, which merely record the transient expulsion of fluids from sedimentary basins, seafloor phase reversals indicate the presence of gas in marine sediment at the time of survey acquisition. They therefore are of significance to engineering and site survey operations as well as the identification of biological communities and gas flux calculations. [ABSTRACT FROM AUTHOR]

Australia is recovering from a disastrous fire season that may prove to be the new normal as the planet continues to heat up. In Queensland, New South Wales and Victoria, more than 1 billion animals and 3500 homes were burned in 160,000 km SP 2 sp (approximately equal to the area of the state of California). This was followed by a huge dust storm and unseasonal heavy rain that caused extensive flooding and dropped large quantities of red mud over Victoria and New South Wales. [Extracted from the article]

The IAWS Executive Committee was invited to Moscow to participate in the celebrations of the 100th anniversary of the foundation of Mytishchi Branch of Bauman Moscow State Technical University hosted by IAWS Fellow and Director Professor Viktor Sanaev. Fellow Sanaev was awarded the IAWS Lecture at this symposium and presented "Interaction Of Wood With Protective-Decorative Materials". The next IAWS Plenary Meeting will be held in South Korea as a fitting start to the first term of the new IAWS President Yoon-Soo Kim who will take over from me on June 2, 2020. [Extracted from the article]

Overactive bladder and urgency incontinence are common conditions generally treated with oral anticholinergic therapy. Despite the development of new antimuscarinic agents, many patients do not tolerate or fail to respond to oral therapy. Intravesical instillation therapy can provide an alternative method of managing bladder overactivity. Intravesical instillation of anticholinergics such as oxybutynin and atropine can achieve cholinergic blockade without producing systemic side effects. Botulinum A toxin injected directly into the detrusor has been shown in preliminary studies to increase bladder capacity and decrease uncontrolled bladder contractility for up to 6 months. Intravesical local anesthetics such as lidocaine and bupivacaine block the conduction of unmyelinated C fibers and when administered into the bladder, lead to an increase in functional bladder capacity. Intravesical capsaicin and resiniferatoxin also affect afferent innervation by blocking C-fiber afferents, leading to decreased bladder contractility and increased bladder capacity. Intravesical instillation therapy can provide an alternative treatment for the management of overactive bladder. [ABSTRACT FROM AUTHOR]

Overactive bladder and urgency incontinence are common conditions generally treated with oral anticholinergic therapy. Despite the development of new antimuscarinic agents, many patients do not tolerate or fail to respond to oral therapy. Intravesical instillation therapy can provide an alternative method of managing bladder overactivity. Intravesical instillation of anticholinergics such as oxybutynin and atropine can achieve cholinergic blockade without producing systemic side effects. Botulinum A toxin injected directly into the detrusor has been shown in preliminary studies to increase bladder capacity and decrease uncontrolled bladder contractility for up to 6 months. Intravesical local anesthetics such as lidocaine and bupivacaine block the conduction of unmyelinated C fibers and when administered into the bladder, lead to an increase in functional bladder capacity. Intravesical capsaicin and resiniferatoxin also affect afferent innervation by blocking C-fiber afferents, leading to decreased bladder contractility and increased bladder capacity. Intravesical instillation therapy can provide an alternative treatment for the management of overactive bladder. [ABSTRACT FROM AUTHOR]

Type I antifreeze proteins (AFPs) are alanine-rich α-helical polypeptides found in some species of right-eye flounders, sculpin, and snailfish. In this study, a shorthorn sculpin skin type I cDNA clone was used to probe an Atlantic snailfish liver cDNA library in order to locate expressed genes corresponding to snailfish plasma AFPs. Clones isolated from the cDNA library had sections with substantial amino acid and nucleotide sequence similarity to snailfish type I AFPs. However, further analysis revealed that the positives were actually three different liver-expressed proteins—two were eggshell proteins, while the third was a type II keratin. We propose that a shift in reading frame could produce alanine-rich candidate AFPs with possible antifreeze activity or ice crystal modification properties. Furthermore, it is plausible that one or more of the liver-expressed proteins represent the progenitors of snailfish type I AFPs. [ABSTRACT FROM AUTHOR]

Selenium (Se) is an essential nutrient, but in higher concentrations can reduce recruitment in fish populations by increasing rates of deformities during early development. Recent work has identified elevated levels of Se in water and biota collected downstream from coal mining activity in Alberta's northeast slopes region. We also recently identified increased incidence of terata and edema in rainbow trout and brook trout with elevated tissue Se from this area. However, there is currently no information regarding the potential for Se to contribute to declining stocks of bull trout, a species of concern in the area. The present study provides an assessment of the potential for Se to contribute to low recruitment in bull trout downstream from coal mining activity. Non-destructive muscle biopsy sampling and a sensitive atomic fluorescence analysis technique are used to determine Se. Results indicate that most bull trout (>90%) captured immediately downstream from coal mining activity in the region have concentrations of Se that would be expected to impair recruitment. Additional work is required to determine the extent of Se's contribution to low recruitment in bull trout. [ABSTRACT FROM AUTHOR]

Shows that the most effective responses were elicited by a replication-incompetent Ad5 vector, used either alone or as a booster inoculation after priming with a DNA vector. Assessment of several vaccine vector delivery systems; Outcome of immunization and viral challenge studies conducted in rhesus macaque monkeys.