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Canine vector-borne infections (CVBIs) are a global health problem. The military working dogs of Sri Lanka die at an early age, and CVBIs have been a leading speculated cause. We examined CVBIs in the working dogs of the Sri Lanka air force (SLAF) and free-roaming dogs (FRDs) and privately owned dogs (PODs) country-wide. Giemsa-stained smears were prepared and conventional PCR-positive DNA was subjected to sequencing and phylogeny. Of the 668 dogs sampled, 212 (31.7%) had one or more CVBIs. The prevalence of infections among the FRDs (40.0%) was significantly higher than SLAF working dogs (30.0%; χ2 = 10.5216; p = 0.0012) and PODs (26.2%; χ2 = 5.3414, p = 0.0208) but not between SLAF dogs and PODs (χ2 = 1.7655, p = 0.1838). Many infected dogs were asymptomatic (57.4%), which was higher among the FRDs. Seven infectious agents were identified: Babesia gibsoni, B. canis, Ehrlichia canis, Anaplasma platys, Leishmania sp., Hepatozoon canis, and filaria worms. The most common infection was B. gibsoni (13.8%), followed by E. canis (9.9%). Three tick species: Rhipicephalus linneai, Rhipicephalus haemaphysaloides and Haemophysalis bispinosa were found infesting the dogs. The SLAF dogs were thoroughly quarantined upon arrival, but the infection prevalence was similar to PODs. [ABSTRACT FROM AUTHOR]

Canine vector-borne infections (CVBIs) are a global health problem. The military working dogs of Sri Lanka die at an early age, and CVBIs have been a leading speculated cause. We examined CVBIs in the working dogs of the Sri Lanka air force (SLAF) and free-roaming dogs (FRDs) and privately owned dogs (PODs) country-wide. Giemsa-stained smears were prepared and conventional PCR-positive DNA was subjected to sequencing and phylogeny. Of the 668 dogs sampled, 212 (31.7%) had one or more CVBIs. The prevalence of infections among the FRDs (40.0%) was significantly higher than SLAF working dogs (30.0%; χ2 = 10.5216; p = 0.0012) and PODs (26.2%; χ2 = 5.3414, p = 0.0208) but not between SLAF dogs and PODs (χ2 = 1.7655, p = 0.1838). Many infected dogs were asymptomatic (57.4%), which was higher among the FRDs. Seven infectious agents were identified: Babesia gibsoni, B. canis, Ehrlichia canis, Anaplasma platys, Leishmania sp., Hepatozoon canis, and filaria worms. The most common infection was B. gibsoni (13.8%), followed by E. canis (9.9%). Three tick species: Rhipicephalus linneai, Rhipicephalus haemaphysaloides and Haemophysalis bispinosa were found infesting the dogs. The SLAF dogs were thoroughly quarantined upon arrival, but the infection prevalence was similar to PODs. [ABSTRACT FROM AUTHOR]

Wawekale Rainforest Reserve (WRR) is a primary lowland tropical rainforest area in the Western Province of Sri Lanka, established with diversity, but disturbed by human activities such as rubber cultivation, logging, poaching, chemical release, and the collection of firewood. Visual Encounter Surveys (VES) were conducted for 100 hours in the year 2022, which covered wide habitat distribution. The herpetofaunal diversity was measured in the WRR which can indicate broader ecological shifts, environmental changes, or habitat degradation. Water quality was measured in the WRR area to determine the ecosystem health and human impact. The study reports 171 species in 73 families, including two Critically Endangered (1.17%), six Endangered (3.51%), 16 Vulnerable (9.36%), and 14 Near Threatened (8.19%) species according to the IUCN Red List. The study area showed 51 endemic faunal species in Sri Lanka, which represented 29.83% of endemism. Based on the observations conducted on the herpetofauna diversity, the Shannon-Wiener diversity index (H) was calculated and the overall herpetofauna (H'H) showed high diversity within the forest premises. The water quality of the forest fragment had an influence from anthropogenic activities such as removing forest cover, bathing, washing vehicles, and releasing agro-chemical compounds resulting in high water temperature, basic pH level, high electrical conductivity, and high total dissolved solid conditions. The WRR, designated under protection, exhibits the need for immediate remedial actions to mitigate human-induced pollution and deforestation, emphasizing the critical importance of implementing proactive conservation measures to sustain ecological integrity and preserve biodiversity. [ABSTRACT FROM AUTHOR]

Findings from experiments that used hydrostatic pressure changes to analyse the process of skeletal muscle contraction are re-examined. The force in resting muscle is insensitive to an increase in hydrostatic pressure from 0.1 MPa (atmospheric) to 10 MPa, as also found for force in rubber-like elastic filaments. The force in rigour muscle rises with increased pressure, as shown experimentally for normal elastic fibres (e.g., glass, collagen, keratin, etc.). In submaximal active contractions, high pressure leads to tension potentiation. The force in maximally activated muscle decreases with increased pressure: the extent of this force decrease in maximal active muscle is sensitive to the concentration of products of ATP hydrolysis (Pi—inorganic phosphate and ADP—adenosine diphosphate) in the medium. When the increased hydrostatic pressure is rapidly decreased, the force recovered to the atmospheric level in all cases. Thus, the resting muscle force remained the same: the force in the rigour muscle decreased in one phase and that in active muscle increased in two phases. The rate of rise of active force on rapid pressure release increased with the concentration of Pi in the medium, indicating that it is coupled to the Pi release step in the ATPase-driven crossbridge cycle in muscle. Pressure experiments on intact muscle illustrate possible underlying mechanisms of tension potentiation and causes of muscle fatigue. [ABSTRACT FROM AUTHOR]

Background: The prevalence of the oral-systemic relationship has accounted for potentially preventable chronic conditions and morbidity worldwide. Health literacy is a large contributing factor. This systematic review investigates the knowledge and awareness of patients with major systemic conditions, regarding the oral associations to their condition.Methods: Electronic databases including Medline (Ovid), CINAHL, The Cochrane Library, Web of Science, Informit Health Databases and Scopus were searched. All articles from 2011 to 2020, investigating knowledge of the oral-systemic link, of adult patients with the following major system conditions were searched: diabetes mellitus (DM), respiratory disease, cardiovascular disease (CVD), pregnancy and bone disease. Two independent reviewers completed screening, data extraction and quality assessment. A synthesis without meta-analysis was conducted. Twenty-four studies, from 14 different countries, were included in the systematic review.Results: Analysis showed that globally, patients with major systemic conditions have poor knowledge and awareness (< 50%) of the oral health associations to their condition. Improvements in health education are particularly necessary for patients with heart disease, bone disease and diabetes. Dentists and the media were the most common source of information. There were no relevant studies investigating the knowledge of patients with respiratory disease.Conclusion: To improve the global burden of preventable chronic conditions, it is essential to address inequalities in the dissemination of health education to at-risk populations. Improvements in patient education rely on an increase in patient-practitioner communication on the oral-systemic link, implementation of oral health educational programs and greater interdisciplinary collaboration. [ABSTRACT FROM AUTHOR]

Development of human leishmaniasis is dependent on the ability of intracellular Leishmania parasites to spread and enter macrophages. The mechanism through which free promastigotes and amastigotes bind and enter host macrophages has been previously investigated; however, little is known about intracellular trafficking and cell‐to‐cell spreading. In this study, the mechanism involved in the spreading of Leishmania aethiopica and Leishmania mexicana was investigated. A significant increase in phosphatidylserine (PS) exhibition, cytochrome C release, and active caspase‐3 expression was detected (P < 0.05) during L. aethiopica, but not L. mexicana spreading. A decrease (P < 0.05) of protein kinase B (Akt) protein and BCL2‐associated agonist of cell death (BAD) phosphorylation was also observed. The nuclear factor kappa‐light‐chain enhancer of activated B cells (NF‐kB) signaling pathway and pro‐apoptotic protein protein kinase C delta (PKC‐δ) were downregulated while inhibition of caspase‐3 activation prevented L. aethiopica spreading. Overall suggesting that L. aethiopica induces host cell's apoptosis during spreading in a caspase‐3‐dependent manner. The trafficking of amastigotes within macrophages following cell‐to‐cell spreading differed from that of axenic parasites and involved co‐localization with lysosomal‐associated membrane protein 1 (LAMP‐1) within 10 min postinfection. Interestingly, following infection with axenic amastigotes and promastigotes, co‐localization of parasites with LAMP‐1‐positive structures took place at 1 and 4 h, respectively, suggesting that the membrane coat and LAMP‐1 protein were derived from the donor cell. Collectively, these findings indicate that host cell apoptosis, demonstrated by PS exhibition, caspase‐3 activation, cytochrome C release, downregulation of Akt, BAD phosphorylation, NF‐kB activation, and independent of PKC‐δ expression, is involved in L. aethiopica spreading. Moreover, L. aethiopica parasites associate with LAMP‐rich structures when taken up by neighboring macrophages. [ABSTRACT FROM AUTHOR]

The physical properties of a liquid in contact with a solid are largely determined by the solid-liquid surface tension. This is especially true for nanoscale systems with high surface area to volume ratios. While experimental techniques can only measure surface tension indirectly for nanoscale systems, computer simulations offer the possibility of a direct evaluation of solid-liquid surface tension although reliable methods are still under development. Here we show that using a mean field approach yields great physical insight into the calculation of surface tension and into the precise relationship between surface tension and excess solvation free energy per unit surface area for nanoscale interfaces. Previous simulation studies of nanoscale interfaces measure either excess solvation free energy or surface tension, but these two quantities are only equal for macroscopic interfaces. We model the solid as a continuum of uniform density in analogy to Hamaker’s treatment of colloidal particles. As a result, the Hamiltonian of the system is imbued with parametric dependence on the size of the solid object through the integration limits for the solid-liquid interaction energy. Since the solid-liquid surface area is a function of the size of the solid, and the surface tension is the derivative of the system free energy with respect to this surface area, we obtain a simple expression for the surface tension of an interface of arbitrary shape. We illustrate our method by modeling a thin nanoribbon and a solid spherical nanoparticle. Although the calculation of solid-liquid surface tension is a demanding task, the method presented herein offers new insight into the problem, and may prove useful in opening new avenues of investigation. [ABSTRACT FROM AUTHOR]

Problem: The increasing specialisation of medical care in larger centres is contributing to the declining use of rural hospitals that are close to larger centres, risking bed closures or even facility closure. Design: An allied health‐led model of care supported by telehealth geriatrician services was developed and implemented in eight beds in a rural hospital to manage older patients needing geriatric evaluation and management. Setting: The project was set in Kilcoy Hospital, a small facility north of Caboolture in Queensland, Australia. The feeder hospital was Caboolture Hospital, the regional centre. Key measures for improvement: Occupancy rates at the rural hospital along with length of stay, discharge destination and functional independence measure. Strategies for change: A project officer was employed 1 day a week to facilitate the implementation of the new model of care. Training and education were provided to medical and nursing staff to understand and implement the geriatric evaluation and management model of care. Effects of change: Over the project time frame, 93 patients were successfully managed in the rural hospital with improved occupancy rates. Outcomes were as effective and safe as compared to the group managed at the regional centre. The model of care is now routine practice. Lessons learnt: Using excess capacity in rural hospitals by employing a geriatric evaluation and management approach is a viable strategy to address declining rural hospital usage. [ABSTRACT FROM AUTHOR]

• Preparation of coconut shell ash to replace cement. • Physical, chemical and microstructural properties of coconut shell ash and concrete. • Structural performance evaluation and environmental impact assessment of concrete. • Optimal replacement level of coconut shell ash to achieve defined structural performance. Concrete is a major construction material with a significant environmental impact. Among other materials, coconut shell ash could be used as a partial replacement of cement to produce sustainable concrete. This study aimed to investigate the use of coconut shell ash as a partial cement replacement to reduce the environmental impact whilst achieving the predefined structural performance of concrete. The fresh, hardened and microstructural properties were investigated, and a life cycle assessment within the product stage was conducted in this study. When considering 15%, 20%, 25% and 30% replacement level concrete mixes, compressive strength was 27.31 MPa, 26.94 MPa, 25.60 MPa and 21.40 MPa at 28 days and environmental impact reduction in global warming potential were over 10%, 15%, 20% and 25% respectively. Based on the structural performance and environmental impact, 20% was the optimal replacement level. Therefore, cement can be replaced by coconut shell ash up to 20% to achieve the average target compressive strength as 25 MPa by reducing the environmental impact in global warming potential over 15%. [ABSTRACT FROM AUTHOR]

In this study, a new approach for predicting damage and specific failure modes in laminated fiber reinforced composites is presented. The new method is based on the peridynamic theory and models individual plies, and represents fiber and matrix materials in each ply explicitly. These features enable analysis of laminates with arbitrary fiber orientation in a convenient manner. Additionally, a new failure mode identification algorithm has been developed and implemented. Instead of the conventional peridynamic damage parameter, the new algorithm works with individual broken bonds, which makes identification of different failure modes including matrix cracking, fiber breakage, and delamination straight-forward and unambiguous. The new peridynamic approach is demonstrated by considering the low-velocity impact damage on composite laminates with and without translaminar reinforcements. The translaminar reinforcement technique considered in this study is z-pinning; two different geometric configurations of z-pins are explored. The impact testing and the post-impact nondestructive evaluations with ultrasonic c-scans are performed at the Air Force Research Laboratory to characterize the delaminations. The impact tests on different samples are simulated using the current peridynamic approach. The predicted impact damage failure modes are compared against the experimental measurements. The new approach is shown to capture low-velocity impact damage both quantitatively and qualitatively. [ABSTRACT FROM AUTHOR]

Hydrological responses vary spatially and temporally according to watershed characteristics. In this study, the hydrological models that we developed earlier for the Little Miami River (LMR) and Las Vegas Wash (LVW) watersheds in the USA were used for detailed sensitivity analyses. To compare the relative sensitivities of the hydrological parameters of these two models, we used normalized root mean square error (NRMSE). By combining the NRMSE index with the flow duration curve analysis, we derived an approach to measure parameter sensitivities under different flow regimes. Results show that the parameters related to groundwater are highly sensitive in the LMR watershed, whereas the LVW watershed is primarily sensitive to near-surface and impervious parameters. The high and medium flows are more impacted by most of the parameters. The low flow regime was highly sensitive to groundwater-related parameters. Moreover, our approach is found to be useful in facilitating model development and calibration. EDITOR D. Koutsoyiannis ASSOCIATE EDITOR S. Huang [ABSTRACT FROM AUTHOR]

Osteoporosis and cardiovascular disease (CVD) share common risk factors, yet both are usually underdiagnosed in the absence of major complications. We investigated associations between arterial stiffness, cardiac workload, carotid intima media thickness (CIMT) and areal bone mineral density (aBMD) in Indian adults. Men and women aged >45 years from the Andhra Pradesh Children and Parents Study (APCAPS) were included for cross-sectional analysis (521 women and 696 men). Dual energy x-ray absorptiometry (DXA) measured aBMD at the whole body, total hip and lumbar spine. Supine blood pressure and heart rate were measured and used to calculate rate pressure product and pulse pressure; augmentation index, pulse wave velocity and CIMT were measured. Sex-interactions were tested (denoted as p-int); adjustments were made for confounders. Data were expressed as SD differences with 95 % confidence intervals. There were significant negative associations between pulse pressure and aBMD at all sites in women only. In unadjusted analyses, for every 1SD increase in pulse pressure, women had greater negative differences in aBMD at the whole body (−0.13 vs 0.007), total hip (−0.20 vs −0.05) and lumbar spine (−0.12 vs 0.05) compared with men. After adjustments, sex differences remained. Similar negative associations were seen between pulse wave velocity and augmentation index with aBMD in women only. There were no sex differences between CIMT and rate pressure product with aBMD. Markers of arterial stiffness are associated with poorer bone health in Indian women, but not in men. There is a need to identify the shared risk factors and markers of arterial stiffness and poor bone health to detect those who require co-management of these diseases to prevent cardiovascular events and fractures. • There are sex differences in cardiac and bone health associations in India. • Arterial stiffness is associated with poorer bone health in Indian women, not men. • Identifying shared risk factors is critical for co-management of CVD and bone health. [ABSTRACT FROM AUTHOR]

Computational results on the panel size effect in the compression after impact (CAI) deformation and damage are presented in this paper. The experimental counterpart of this paper is Lin et al. (2022). The in-plane sizes studied are 152.4 mm × 101.6 mm, 177.8 mm × 177.8 mm, and 330.2 mm × 330.2 mm. The thicknesses studied are 24-ply (3.1 mm) and 48-ply (6.2 mm). The two stacking sequences are [45/-45/0/90/0/0] ns and [45/0/-45/90] ns. The material system studied is IM7/977-3. Enhanced Schapery Theory with 2D plane stress states (2D EST) have been used for the progressive failure analyses. Predicted LVI-induced damage was transferred onto the CAI mesh based on a damage transferring algorithm. The results show that 2D EST can successfully capture the deformation and CAI-induced damage patterns of the panels with various sizes. With detailed computational results, different mechanisms for the CAI failure have been analyzed and categorized. A more rigorous and practical term — compressive load-bearing capacity after impact (CLBCAI) has been proposed to replace compressive strength after impact (CSAI) to account for the effects of impact damage and panel geometry. This paper provides results to show that the existing industrial standard D7137 (2017) is limited and may need to be replaced. • Study performed on panel size effects on Compressive Load bearing capacity of composite laminates. • A predictive numerical framework is developed and results compared against experiments. • The model captured the observed effects with full failure sequences. • A 3D-EST model (extension) development is suggested for future work. [ABSTRACT FROM AUTHOR]

A computational study of the low velocity impact (LVI) responses and damage of IM7/977-3 composite laminates with various geometry parameters is presented in this paper. The in-plane sizes of the laminates are 152.4 mm × 101.6 mm, 177.8 mm × 177.8 mm, and 330.2 mm × 330.2 mm. The two panel thicknesses are 24-ply (3.1 mm) and 48-ply (6.2 mm). The two panel layups are [45/−45/0/90/0/0] ns and [45/0/−45/90] ns. Detailed experimental results have been reported in Lin et al. (2022). Two versions of Enhanced Schapery Theory with inelasticity (EST-InELA) implemented with 2D plane stress states and 3D stress states are applied to predict the LVI responses and damage. It is found that the EST models are able to predict most of the LVI-induced damage features accurately and the thickness-to-length/width ratio is identified as the most important geometric factor affecting the LVI responses and damage. Comparing the numerical results, 2D EST-InELA is more accurate in predicting the LVI-induced damage while 3D EST-InELA performs better in predicting the impact energy absorption. In addition, 2D EST-InELA is significantly more efficient than 3D EST-InELA. Recommendations for model applications are given towards the end of this paper. The results presented here capture the experimental results (Lin et al., 2022) with respect to panel size effects suggesting revisions to existing standards (ASTM-D7136, 2005). [ABSTRACT FROM AUTHOR]

The minichromosome maintenance (MCM) complex is the conserved helicase motor of the eukaryotic replication fork. Mutations in the Mcm4 subunit are associated with replication stress and double strand breaks in multiple systems. In this work, we characterize a new temperature-sensitive allele of Schizosaccharomyces pombe mcm4+. Uniquely among known mcm4 alleles, this mutation causes sensitivity to the alkylation damaging agent methyl methanesulfonate (MMS). Even in the absence of treatment or temperature shift, mcm4-c106 cells show increased repair foci of RPA and Rad52, and require the damage checkpoint for viability, indicating genome stress. The mcm4-c106 mutant is synthetically lethal with mutations disrupting fork protection complex (FPC) proteins Swi1 and Swi3. Surprisingly, we found that the deletion of rif1+ suppressed the MMS-sensitive phenotype without affecting temperature sensitivity. Together, these data suggest that mcm4-c106 destabilizes replisome structure. [ABSTRACT FROM AUTHOR]

Fe-S clusters, essential cofactors needed for the activity of many different enzymes, are assembled by conserved protein machineries inside bacteria and mitochondria. As the architecture of the human machinery remains undefined, we co-expressed in Escherichia coli the following four proteins involved in the initial step of Fe-S cluster synthesis: FXN42-210 (iron donor); [NFS1]·[ISD11] (sulfur donor); and ISCU (scaffold upon which new clusters are assembled). We purified a stable, active complex consisting of all four proteins with 1:1:1:1 stoichiometry. Using negative staining transmissionEMand single particle analysis, we obtained a three-dimensional model of the complex with ~14 Å resolution. Molecular dynamics flexible fitting of protein structures docked into the EM map of the model revealed a [FXN42-210]24·[NFS1]24·[ISD11]24·[ISCU]24 complex, consistent with the measured 1:1:1:1 stoichiometry of its four components. The complex structure fulfills distance constraints obtained from chemical cross-linking of the complex at multiple recurring interfaces, involving hydrogen bonds, salt bridges, or hydrophobic interactions between conserved residues. The complex consists of a central roughly cubic [FXN42-210]24· [ISCU]24 sub-complex with one symmetric ISCU trimer bound on top of one symmetric FXN42-210 trimer at each of its eight vertices. Binding of 12 [NFS1]2·[ISD11]2 sub-complexes to the surface results in a globular macromolecule with a diameter of ~15 nm and creates 24 Fe-S cluster assembly centers. The organization of each center recapitulates a previously proposed conserved mechanism for sulfur donation from NFS1 to ISCU and reveals, for the first time, a path for iron donation from FXN42-210 to ISCU. [ABSTRACT FROM AUTHOR]

The biosynthesis of Fe-S clusters is a vital process involving the delivery of elemental iron and sulfur to scaffold proteins via molecular interactions that are still poorly defined. We reconstituted a stable, functional complex consisting of the iron donor, Yfh1 (yeast frataxin homologue 1), and the Fe-S cluster scaffold, Isu1, with 1:1 stoichiometry, [Yfh1]24·[Isu1]24. Using negative staining transmission EM and single particle analysis, we obtained a three-dimensional reconstruction of this complex at a resolution of ~17 Å. In addition, via chemical cross-linking, limited proteolysis, and mass spectrometry, we identified protein- protein interaction surfaces within the complex. The data together reveal that [Yfh1]24·[Isu1]24 is a roughly cubic macromolecule consisting of one symmetric Isu1 trimer binding on top of one symmetric Yfh1 trimer at each of its eight vertices. Furthermore, molecular modeling suggests that two subunits of the cysteine desulfurase, Nfs1, may bind symmetrically on top of two adjacent Isu1 trimers in a manner that creates two putative [2Fe-2S] cluster assembly centers. In each center, conserved amino acids known to be involved in sulfur and iron donation by Nfs1 and Yfh1, respectively, are in close proximity to the Fe-S cluster-coordinating residues of Isu1. We suggest that this architecture is suitable to ensure concerted and protected transfer of potentially toxic iron and sulfur atoms to Isu1 during Fe-S cluster assembly. [ABSTRACT FROM AUTHOR]

The silky shark, Carcharhinus falciformis, is a cosmopolitan species commonly caught as a bycatch for longline fisheries. However, the genetic stock structure for the Indo-Pacific Ocean is not well-defined yet. Here, we used eight microsatellite loci to examine the genetic stock structure and effective population size of 307 silky sharks across 5 Indo-Pacific sampling locations. A major genetic break was found between Aceh and the remaining locations (FST = 0.0505–0.0828, p = 0.001). The Indian Ocean displayed a slightly lower effective population estimate (Ne) compared to the Pacific Ocean, potentially due to the higher fishing pressure in the Indian Ocean region. The lowest Ne was found in the Aceh population (Ne = 2.3), suggesting it might be a small and endemic population. These findings offer valuable information for the conservation and management of the silky shark. We suggest that the population around Aceh waters constitutes a distinct stock and should be managed independently. Further investigations into migratory and movement patterns are needed to define the boundaries of different stocks, ensuring effective management the silky shark across the Indo-Pacific region. [ABSTRACT FROM AUTHOR]

Abstract An objective approach is presented for determining peridynamic (PD) material parameters for the nonlinear pre-peak behavior of fiber-reinforced composite laminates. The fiber and matrix material regions are explicitly represented. The pre-peak behavior of laminae exhibiting different degrees of nonlinearity depending on the fiber orientation is represented by the PD adaptations of the Ramberg–Osgood (RO) and hyperbolic relationships. The approach is extended to capture the nonlinear inter-laminar response for laminates. The PD method is validated against experiments for several off-axis composite coupons under quasi-static tension. The current approach accurately captures the nonlinear pre-peak material behavior of fiber-reinforced composites. [ABSTRACT FROM AUTHOR]

An experimental study of the LVI responses of flat composite panels of different in-plane sizes is reported in this paper. The studied samples vary in the in-plane size, thickness, and stacking sequence. The three studied in-plane sizes are 152.4 mm × 101.6 mm, 177.8 mm × 177.8 mm, and 330.2 mm × 330.2 mm. The two thicknesses are 24-ply and 48-ply. The two stacking sequences are [45/-45/0/90/0/0] ns and [45/0/-45/90] ns. The material system is IM7/977-3. Experimental results including load responses, 3D digital image correlation (DIC), surface inspections, ultrasound C-scanning, and X-ray μ CT are presented. It is found that the studied layups (two) have little effect on the load responses but change the LVI-induced damage morphology significantly. The thickness-to-length/width ratio is identified as the most important geometric parameter influencing the LVI responses and damage. However, the investigated panel size effects are only on the load responses and damage sizes, but not on the detailed damage features characterized by μ CT, implying that the LVI damage mechanisms are unaffected. The panel size effects reported in this paper show that the existing industrial standard (ASTM D7136, 2005) that focuses on single-size (152.4 mm × 101.6 mm) samples may require revision as demonstrated in part II of this two-part paper. [ABSTRACT FROM AUTHOR]

This paper is part II of a study on the CAI responses of laminated composite panels. Panels with three in-plane sizes, two thicknesses, and two stacking sequences were studied using CAI fixtures based on and modified from the industrial standard. The three in-plane sizes are 152.4 mm × 101.6 mm, 177.8 mm × 177.8 mm, and 330.2 mm × 330.2 mm. The two thicknesses are 24-ply and 48-ply. The two stacking sequences are [45/-45/0/90/0/0] ns and [45/0/-45/90] ns. The material system is IM7/977-3. Load–displacement curves, 2D/3D DIC characterization, and ultrasound C-scans are presented. Two types of CAI deformation patterns have been observed. The first type of deformation is mostly in-plane with local buckling, and its corresponding CAI-induced failure concentrates around the impacted plate center. The second type of deformation is with global buckling, and the corresponding CAI-induced failure is unrelated to the LVI-induced damage footprints. Three driving forces for the CAI failure have been identified: LVI-induced damage, global buckling-induced excessive bending, and delamination of the lateral edges. The dominant driving force is dependent on the panel's thickness-to-length/width ratio, which is found to be the most important geometric parameter affecting the CAI behavior. The experimental results imply that the standard coupon-size (152.4 mm × 101.6 mm) CAI test results do not accurately represent the compressive load-carrying capacity of a composite panel subjected to impact damage. The results reported in this paper call for a re-examination and revision of the existing industrial standard ASTM D7137 (2017) to assess CAI load-carrying capacity. [ABSTRACT FROM AUTHOR]

Key points Muscle performance increases with temperature in a wide variety of animals but has been studied most fully in frogs and mammals., While it has been previously proposed that the tension-generating step in the muscle crossbridge cycle is temperature-sensitive, this does not explain why tension increases after a rapid temperature rise much more slowly than after a length step., We have developed a model of an unbranched crossbridge cycle that simulates the effects of temperature on the tension and force-velocity relationship of frog muscle and the tension rise after a rapid temperature rise., We conclude that the increased tension produced by raising temperature is principally due to enhancement of the two steps before the tension-generating step., By integrating the interpretation of several key physiological experiments, this simplifies our understanding of the crossbridge cycle and the effect of temperature on human muscle performance., Abstract The isometric tetanic tension of skeletal muscle increases with temperature because attached crossbridge states bearing a relatively low force convert to those bearing a higher force. It was previously proposed that the tension-generating step(s) in the crossbridge cycle was highly endothermic and was therefore itself directly targeted by changes in temperature. However, this did not explain why a rapid rise in temperature (a temperature jump) caused a much slower rate of rise of tension than a rapid length step. This led to suggestions that the step targeted by a temperature rise is not the tension-generating step but is an extra step in the attached pathway of the crossbridge cycle, perhaps located on a parallel pathway. This enigma has been a major obstacle to a full understanding of the operation of the crossbridge cycle. We have now used a previously developed mechano-kinetic model of the crossbridge cycle in frog muscle to simulate the temperature dependence of isometric tension and shortening velocity. We allowed all five steps in the cycle to be temperature-sensitive. Models with different starting combinations of enthalpy changes and activation enthalpies for the five steps were refined by downhill simplex runs and scored by their ability to fit experimental data on the temperature dependence of isometric tension and the relationship between force and shortening velocity in frog muscle. We conclude that the first tension-generating step may be weakly endothermic and that the rise of tension with temperature is largely driven by the preceding two strongly endothermic steps of ATP hydrolysis and attachment of M.ADP.Pi to actin. The refined model gave a reasonable fit to the available experimental data and after a temperature jump the overall rate of tension rise was much slower than after a length step as observed experimentally. The findings aid our understanding of the crossbridge cycle by showing that it may not be necessary to include an additional temperature-sensitive step. [ABSTRACT FROM AUTHOR]

Thedesign and solid-phase synthesis of tetrahydropyridazine-3,6-dione(Tpd) peptidomimetics derived from backbone-aminated peptides is reported.The described protocol features the synthesis of chiral α-hydrazinoacids suitable for chemoselective incorporation into growing peptidechains. Acid-catalyzed cyclization to form the Tpd ring during cleavageaffords the target peptidomimetics in good yield and purity. The scopeof Tpd incorporation is demonstrated through the synthesis of constrainedpeptides featuring nucleophilic/electrophilic side chains and stericallyencumbered α-substituted hydrazino acid residues. [ABSTRACT FROM AUTHOR]

Activation of the ER stress response is associated with malignant progression of B cell chronic lymphocytic leukemia (CLL). We developed a murine CLL model that lacks the ER stress-associated transcription factor XBP-1 in B cells and found that XBP-1 deficiency decelerates malignant progression of CLL-associated disease. XBP-1 deficiency resulted in acquisition of phenotypes that are disadvantageous for leukemic cell survival, including compromised BCR signaling capability and increased surface expression of sphingosine-1-phosphate receptor 1 (S1P1). Because XBP-1 expression requires the RNase activity of the ER transmembrane receptor IRE-1, we developed a potent IRE-1 RNase inhibitor through chemical synthesis and modified the structure to facilitate entry into cells to target the IRE-1/XBP-1 pathway. Treatment of CLL cells with this inhibitor (B-I09) mimicked XBP-1 deficiency, including upregulation of IRE-1 expression and compromised BCR signaling. Moreover, B-I09 treatment did not affect the transport of secretory and integral membrane-bound proteins. Administration of B-I09 to CLL tumor-bearing mice suppressed leukemic progression by inducing apoptosis and did not cause systemic toxicity. Additionally, B-I09 and ibrutinib, an FDA-approved BTK inhibitor, synergized to induce apoptosis in B cell leukemia, lymphoma, and multiple myeloma. These data indicate that targeting XBP-1 has potential as a treatment strategy, not only for multiple myeloma, but also for mature B cell leukemia and lymphoma. [ABSTRACT FROM AUTHOR]

Activation of the ER stress response is associated with malignant progression of B cell chronic lymphocytic leukemia (CLL). We developed a murine CLL model that lacks the ER stress--associated transcription factor XBP-1 in B cells and found that XBP-1 deficiency decelerates malignant progression of CLL-associated disease. XBP-1 deficiency resulted in acquisition of phenotypes that are disadvantageous for leukemic cell survival, including compromised BCR signaling capability and increased surface expression of sphingosine-1-phosphate receptor 1 (S1P1). Because XBP-1 expression requires the RNase activity of the ER transmembrane receptor IRE-1, we developed a potent IRE-1 RNase inhibitor through chemical synthesis and modified the structure to facilitate entry into cells to target the IRE-1/XBP-1 pathway. Treatment of CLL cells with this inhibitor (B-I09) mimicked XBP-1 deficiency, including upregulation of IRE-1 expression and compromised BCR signaling. Moreover, B-I09 treatment did not affect the transport of secretory and integral membrane-bound proteins. Administration of B-I09 to CLL tumor--bearing mice suppressed leukemic progression by inducing apoptosis and did not cause systemic toxicity. Additionally, B-I09 and ibrutinib, an FDA-approved BTK inhibitor, synergized to induce apoptosis in B cell leukemia, lymphoma, and multiple myeloma. These data indicate that targeting XBP-1 has potential as a treatment strategy, not only for multiple myeloma, but also for mature B cell leukemia and lymphoma. [ABSTRACT FROM AUTHOR]

Inositol-requiring enzyme 1 (IRE-1)is a kinase/RNase ER stresssensor that is activated in response to excessive accumulation ofunfolded proteins, hypoxic conditions, calcium imbalance, and otherstress stimuli. Activation of IRE-1 RNase function exerts a cytoprotectiveeffect and has been implicated in the progression of cancer via increasedexpression of the transcription factor XBP-1s. Here, we describe thesynthesis and biological evaluation of novel chromenone-based covalentinhibitors of IRE-1. Preparation of a family of 8-formyltetrahydrochromeno[3,4-c]pyridines was achieved via a Duff formylation thatis attended by an unusual cyclization reaction. Biological evaluationin vitro and in whole cells led to the identification of 30as a potent inhibitor of IRE-1 RNase activity and XBP-1s expressionin wild type B cells and human mantle cell lymphoma cell lines. [ABSTRACT FROM AUTHOR]

The axial spondyloarthropathies are a group of chronic inflammatory diseases that predominantly affect the axial joints. This group includes ankylosing spondylitis and nonradiographic axial spondyloarthropathy. While the pathogenesis of axial spondyloarthropathies is not clear, immunologically active tissues primarily include the entheses, ie, the areas where ligaments, tendons, and joint capsules attach to bone and to the annulus fibrosis at the vertebrae. One of the major mediators of the immune response in this group of diseases is tumor necrosis factor-alpha (TNFα). Blockade of TNFα results in reduced vascularity and inflammatory cell infiltration in the synovial tissues of affected joints. Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-TNFα monoclonal antibody. CZP has unique properties that differ from other available TNFα inhibitors by virtue of its lack of an Fc region, which minimizes potential Fc-mediated effects, and its PEGylation, which improves drug pharmacokinetics and bioavailability. It has been shown in clinical trials that CZP improves patient outcomes and reduces inflammation in the sacroiliac joints and spine in both ankylosing spondylitis and nonradiographic axial spondyloarthropathies. These data support CZP as a treatment option for axial spondyloarthropathies. [ABSTRACT FROM AUTHOR]

In this paper, a traction-separation-based cohesive modeling approach is proposed to predict the effect of z-pinning on laminated composites. A detailed experimental characterization of the z-pin pullout process using the flatwise tension test is presented. Utilizing these flatwise tension results, numerical simulation of the progressive damage due to delaminations in a double cantilever beam with z-pinning has been performed. Experimental details of the z-pinned double cantilever beams are presented for IM7/977-3 graphite/epoxy. The approach taken in this study utilizing the cohesive elements within the Abaqus® finite element software has proven that the models can predict the behavior of z-pinned composites close to experimental observations. It was found that the discretization of the fracture resistance curve along the z-pin field is essential to capture the dynamics of the delamination accurately. [ABSTRACT FROM AUTHOR]

Abstract: Long-term poultry litter (PL) application in pasture soil was found to enhance accumulation of certain phosphorus (P) forms in soil micro-aggregate fractions and have potential impacts on non-point water pollution by wind erosion or run-off. A P fractionation method was utilized to identify P forms in aggregate fractions derived from a long-term PL applied pasture soil. Enrichment of surface soil P by PL application has considerable effects on increasing specifically the labile P forms in surface soil micro-aggregates. Particular concern is of accumulation of water soluble and labile inorganic P forms in micro-aggregate particles susceptible to wind and soil erosion. Continuous application of PL to pasture fields for at least 15years at a rate of 2.3Tha−1 y−1 resulted in a considerable increase in inorganic P forms including Mehlich-3, water soluble and labile bicarbonate P (NaHCO3–P) forms in most aggregate size fractions. Mehlich-3-P was highest in <0.053mm micro-aggregates (223.8mgkg−1) and relatively high amounts ranging from 145.5 to 170.4mgkg−1 were found in 0.053–1.0mm micro-aggregates. High levels of water soluble P were found in majority of micro-aggregate particles in PL applied soil, which amounts to 11–18% of total inorganic P in these particles. Bicarbonate–P or labile inorganic P forms were at elevated levels in 0.125–0.25, 0.053–0.125 and <0.053mm micro-aggregates, which amounts to approximately 11–22% of total inorganic P in these particles. The PL application also increased the NaOH extractable P (NaOH–P) or Al/Fe bound P in soil aggregate fractions (192–347mgkg−1). Notable increase in labile organic P forms in certain micro-aggregate size fractions may be of concern due to ease of P mineralization. [Copyright &y& Elsevier]

Lucentamycin A is a marine-derived peptide natural product harboring a unique 4-ethylidene-3-methylproline (Emp) subunit. The proposed structure of lucentamycin A and the core Emp residue have recently been called into question through synthesis. Here, we report the first total synthesis of lucentamycin A, which confirms that the ethylidene substituent in Emp bears an E geometry, in contrast to the originally assigned Z configuration. Synthesis of the desired (E)-Emp subunit required the implementation of a novel strategy starting from Gamer's aldehyde. [ABSTRACT FROM AUTHOR]

IL-10 is an immunoregulatory cytokine expressed by numerous cell types. Studies in mice confirm that different IL-10-expressing cell subsets contribute differentially to disease phenotypes. However, little is known about the relationship between cell- or tissue-specific IL-10 expression and disease susceptibility in humans. In this study, we used the previously described human (h)ILlOBAC transgenic model to examine the role of hIL-10 in maintaining intestinal homeostasis. Genomically controlled hIL-10 expression rescued I&igr;10-/- mice from Helicobacter-'mduced colitis and was associated with control of proinflammatory cytokine expression and Thl7 cell accumulation in gut tissues. Resistance to colitis was associated with an accumulation of hIL-10-expressing CD4+Foxp3+ regulatory T cells specifically within the lamina propria but not other secondary lymphoid tissues. Cotransfer of CD4+CD45RBlo cells from I110-/-/hIL10BAC mice rescued Ragl-/- mice from colitis, further suggesting that CD4+ T cells represent a protective source of hlL-10 in the colon. In concordance with an enhanced capacity to express IL-10, CD4+CD44+ T cells isolated from the lamina propria exhibited lower levels of the repressive histone mark H3K27Me3 and higher levels of the permissive hist one mark acetylated histone H3 in both the human and mouse ILIO locus compared with the spleen. These results provide experimental evidence verifying the importance of T cell-derived hIL-10 expression in controlling inflammation within the colonic mucosa. We also provide molecular evidence suggesting the tissue microenvironment influences IL-10 expression patterns and chromatin structure in the human (and mouse) ILIO locus. The Journal of Immunology, 2012, 189: 1243-1252. [ABSTRACT FROM AUTHOR]

Abstract: Akt is a cardinal nodal point in PI3K signaling pathway and confers resistance to apoptosis through inactivation of regulatory substrates such as GSK3β. Efforts to inhibit the kinase activity of Akt have largely focused on targeting the ATP-binding domain of Akt. Here, we present the design and synthesis of conformationally constrained GSK3β mimics featuring a novel extended dipeptide surrogate core. This effort resulted in the identification of a novel substrate mimetic Akt inhibitor (11) with low micromolar activity in vitro (Akt1 IC50 =3.1μM). [Copyright &y& Elsevier]

Substituted 4-alkylideneprolines represent a rare class of naturally occurring amino acids with promising biological activities. Lucentamycin A is a cytotoxic, marine-derived tripeptide that harbors a 4-ethylidine-3-methylproline (Emp) residue unique among known peptide natural products, hi this paper, we examine the synthesis of Emp and related 4-alkylideneproJines employing a versatile ester enolate--Claisen rearrangement. The scope and selectivity of the key rearrangement reaction are described with a number of diversely substituted glycine ester substrates. Treatment of the allyl esters with excess NaHMDS at ambient temperature gives rise to highly substituted αallylglycine-products -with-good-to-excellent- diastereoselectivities. Resolution- of dipeptide-diastereomers and- cyclization to form the pyrrolidine rings provide rapid access to stereopure prolyl dipeptides. We have applied this strategy to the synthesis of four Emp-containing isomers of lucentamycin A in pursuit of a definitive stereochemical revision of the natural product Our studies indicate that the Emp stereogenic centers are not the source of structural misassignment. The current strategy should find broad utility in the synthesis of additional natural product analogues and related 3-alkyl-4-alkylidene prolines. [ABSTRACT FROM AUTHOR]

Study Objective. To determine if the concomitant use of nelfinavir and proton pump inhibitors (PPIs) in patients with human immunodeficiency virus (HIV) infection results in the loss of virologic control. Design. Retrospective cohort study. Data Source. Pharmacy, laboratory, and administrative databases of a large integrated health care system in northern California. Patients. A total of 1147 HIV-positive adults who started nelfinavir therapy between November 1, 1998, and June 20, 2003; within this cohort, 141 patients (12.3%) were also prescribed PPIs. Measurements and Main Results. The effects on two virologic outcomes-- achievement of undetectable HIV viral load and subsequent virologic rebound--were compared between patients receiving nelfinavir alone and those receiving nelfinavir with PPIs. Cox proportional hazards models were used, with adjustments for age, sex, race, HIV risk factors, hepatitis B or C coinfection, and other concurrent drugs known to affect the metabolism of nelfinavir. The use of PPIs had little effect on the ability to achieve an undetectable HIV viral load (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.58-1.19, p=0.29), but there was an approximate 50% increased risk of virologic rebound with the concurrent use of PPIs (adjusted HR 1.53, 95% CI 1.06-2.19, p=0.02). Short-term use of PPIs (defined as within 30 days of initial PPI dispensation) was not associated with increased risk of virologic rebound (HR 1.07, 95% CI 0.26-4.41, p=0.93) compared with no use of PPIs. Conclusion. Use of PPIs should be minimized or avoided in patients who have attained an undetectable HIV viral load while taking a nelfinavir-based antiretroviral regimen. However, concomitant use of these drugs may be acceptable for indications where PPIs are required for fewer than 30 days. [ABSTRACT FROM AUTHOR]

The basic characteristics of the process of force and power generation in active muscle that have emerged from temperature studies are examined. This is done by reviewing complementary findings from temperature-dependence studies and rapid temperature-jump (T-jump) experiments and from intact and skinned fast mammalian muscle fibres. In isometric muscle, a small T-jump leads to a characteristic rise in force showing that crossbridge force generation is endothermic (heat absorbed) and associated with increased entropy (disorder). The sensitivity of the T-jump force generation to added inorganic phosphate (Pi) indicates that a T-jump enhances an early step in the actomyosin (crossbridge) ATPase cycle before Pi-release. During muscle lengthening when steady force is increased, the T-jump force generation is inhibited. Conversely, during shortening when steady force is decreased, the T-jump force generation is enhanced in a velocity-dependent manner, showing that T-jump force generation is strain sensitive. Within the temperature range of ∼5-35°C, the temperature dependence of steady active force is sigmoidal both in isometric and in shortening muscle. However, in shortening muscle, the endothermic character of force generation becomes more pronounced with increased velocity and this can, at least partly, account for the marked increase with warming of the mechanical power output of active muscle. [ABSTRACT FROM AUTHOR]

Abstract: Scarce surface water resources have led farmers to use groundwater heavily for irrigation in the Murray-Darling Basin of Australia. Saline groundwater is emerging as an alternative source of water for irrigation. This study examines the potential use of saline groundwater for a range of crops. Among cropping groups modelled, oilseeds and grain crops are considerably tolerant to saline groundwater in terms of the change yield with salinity levels, although the tolerance levels are crop-specific. Based on availability of saline groundwater, coarse textured soil, deep water table and moderate rainfall, this study also revealed that twenty-two percent or seven million hectares of the Murray hydrogeological basin in the southern Murray-Darling Basin may be suitable for the saline groundwater irrigation. However, it is also noted that the use of saline groundwater is only feasible for saline-tolerant crops under proper drainage management and by observing suitable precautionary measures. Therefore, the use of saline groundwater in irrigation requires careful attention to monitor the build up of salt in the root zone. [Copyright &y& Elsevier]

Regio- and diastereoselcctive reactions of a homoproline enolate enable the synthesis of novel extended dipeptide surrogates. Bicyclic carbamate 9 and fused β-lactam scaffold II were prepared from L-pyroglutamic acid via substrate-controlled clectrophilic azidation. Synthesis of orthogonally protected hexahydropyrrolizine, hexahydropyrrolizinone. and hexahydropyrroloazepinone dipeptide surrogates relied on allylation of proline derivative 5, followed by Curtius rearrangement to introduce the N-terminal carbamate group. A total of six azabicycloalkane derivatives were evaluated for conformational mimicry of extended dipeptides by a combination of X-ray diffraction and molecular modeling. Analysis of putative backbone dihedral angles and Nto C-terminal dipeptide distances indicate that compounds (α'S)-14b and 21 approximate the conformation of dipeptidcs found in β-sheets. while tripeptide mimic 28 is also highly extended in the solid state. Structural data suggest that ring size and relative stereochemistry have a profound effect on the ability of these scalfolds to act as β-strand mimetics and should inform the design of related conformational probes. [ABSTRACT FROM AUTHOR]

We examined the tension responses to ramp shortening and rapid temperature jump (<0.2 ms, 3–4°C T-jump) in maximally Ca2+-activated rabbit psoas muscle fibres at 8–9°C (the fibre length ( L0) was ∼1.5 mm and sarcomere length 2.5 μm). The aim was to investigate the strain sensitivity of crossbridge force generation in muscle. The T-jump induced tension rise was examined during steady shortening over a wide range of velocities ( V) approaching the Vmax ( V range ∼0.01 to ∼1.5 L0 s−1). In the isometric state, a T-jump induced a biphasic tension rise consisting of a fast (∼50 s−1, phase 2b) and a slow (∼10 s−1, phase 3) component, but if treated as monophasic the rate was ∼20 s−1. During steady shortening the T-jump tension rise was monophasic; the rate of tension rise increased linearly with shortening velocity, and near Vmax it was ∼200 s−1, ∼10× faster than in the isometric state. Relative to the tension reached after the T-jump, the amplitude increased with shortening velocity, and near Vmax it was ∼4× larger than in the isometric state. Thus, the temperature sensitivity of muscle force is markedly increased with velocity during steady shortening, as found in steady state experiments. The rate of tension decline during ramp shortening also increased markedly with increase of velocity. The absolute amplitude of T-jump tension rise was larger than that in the isometric state at the low velocities (<0.5 L0 s−1) but decreased to below that of the isometric state at the higher velocities. Such a biphasic velocity dependence of the absolute amplitude of T-jump tension rise implies interplay between, at least, two processes that have opposing effects on the tension output as the shortening velocity is increased, probably enhancement of crossbridge force generation and faster (post-stroke) crossbridge detachment by negative strain. Overall, our results show that T-jump force generation is strain sensitive and becomes considerably faster when exposed to negative strain. Thus the crossbridge force generation step in muscle is both temperature sensitive (endothermic) and strain sensitive. [ABSTRACT FROM AUTHOR]

The article presents a study on infected and uninfected patients of HIV virus with diagnosis of incident syphilis from Kaiser Permanente Northern California in Oakland, California. It states that compared with HIV-infected patients, HIV-uninfected patients got a higher rate of incident syphilis. It adds that HIV-infected patients were more possible to decrease in rapid plasma reagin (RPR) and have serologic failure. It notes that a regular syphilis test must be done on HIV-infected patients.

A rapid and stereoselective enolate-Claisen rearrangement provides access to the 4-ethylidene-3-methylproline (Emp) subunit of lucentamycin A. Synthesis of the putative structure of the cytotoxic natural product suggests the need for structural revision. [ABSTRACT FROM AUTHOR]

lnterleu kin (IL)-10 is an immunoregulatory cytokine that is produced by diverse cell populations. Studies in mice suggest that the cellular source of IL-10 is a key determinant in various disease pathologies, yet little is known regarding the control of tissue-specific human IL-10 expression. To assess cell type-specific human IL-10 regulation, we created a human IL-10 transgenic mouse with a bacterial artificial chromosome (hIL10BAC) in which the IL10 gene is positioned centrally. Since human IL-10 is biologically active in the mouse, we could examine the in vivo capacity of tissue-specific human IL-10 expression to recapitulate IL-10-dependent phenotypes by reconstituting 1110-/- mice (1110-/-/hIL10BAC). In response to LPS, ll10-/-/hIL10BAC mice proficiently regulate IL-b-target genes and normalize sensitivity to LPS toxicity via faithful human IL-10 expression from macrophages and dendritic cells. However, in the Leishmania donovan! model of pathogen persistence, ll10-/-/hlL10BAC mice did not develop the characteristic lL-10+lFN-γ+CD4 T cell subset thought to mediate persistence and, like ll10-/- mice, cleared the parasites. Furthermore, the IL-10-promoting cytokine IL-27 failed to regulate transgenic human IL-10 production in CD4+ T cells in vitro which together suggests that the hIL10BAC encodes for weak T cell-specific IL-10 expression. Thus, the hIL10BAC mouse is a model of human gene structure and function revealing tissue-specific regulatory requirements for IL-10 expression which impacts disease outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Agriculture is the highest consumer of water resources in Australia. Soil water models play a vital role in agriculture in terms of estimating water use, water allocation and current water status at a given scale. This paper reviews widely-used soil water models developed in Australia over the last three to four decades that have been used to simulate soil water status at various temporal and spatial scales. These models are categorised in terms of their complexity. This paper provides an overview of soil water models and the basic modelling techniques employed by each model. Considerable emphasis is given to matching existing data availability with input data requirements for each model to identify the limitations of model application in terms of data availability. A comprehensive review of the application of soil water models is also given, supported by assessments of individual model performance. The limitations and assumptions made under various approaches to soil water modelling are subsequently examined. Research and policy agencies are focusing more and more on incorporating temporal models into spatial modelling frameworks for natural resources and water management purposes. These are consequently being used much more in the process of policy development. Complex models, whose wide-range application is often hampered by a lack of specific data, should have their processes simplified in order to be accommodated into spatial frameworks where appropriate. Biophysical processes within simple models should consider new data sources and understanding so as to gain more accurate predictions. [Copyright &y& Elsevier]

We examined the tension change induced by a rapid temperature jump (T-jump) in shortening and lengthening active muscle fibres. Experiments were done on segments of permeabilized single fibres (length ( L0) ∼2 mm, sarcomere length 2.5 μm) from rabbit psoas muscle; [MgATP] was 4.6 mm, pH 7.1, ionic strength 200 mm and temperature ∼9°C. A fibre was maximally Ca2+-activated in the isometric state and a ∼3°C, rapid (< 0.2 ms), laser T-jump applied when the tension was approximately steady in the isometric state, or during ramp shortening or ramp lengthening at a limited range of velocities (0–0.2 L0 s−1). The tension increased to 2- to 3 × P0 (isometric force) during ramp lengthening at velocities > 0.05 L0 s−1, whereas the tension decreased to about < 0.5 × P0 during shortening at 0.1–0.2 L0 s−1; the unloaded shortening velocity was ∼1 L0 s−1 and the curvature of the force–shortening velocity relation was high ( a/ P0 ratio from Hill's equation of ∼0.05). In isometric state, a T-jump induced a tension rise of 15–20% to a new steady state; by curve fitting, the tension rise could be resolved into a fast (phase 2b, 40–50 s−1) and a slow (phase 3, 5–10 s−1) exponential component (as previously reported). During steady lengthening, a T-jump induced a small instantaneous drop in tension, followed by recovery, so that the final tension recorded with and without a T-jump was not significantly different; thus, a T-jump did not lead to a net increase of tension. During steady shortening, the T-jump induced a pronounced tension rise and both its amplitude and the rate (from a single exponential fit) increased with shortening velocity; at 0.1–0.2 L0 s−1, the extent of fibre shortening during the T-jump tension rise was estimated to be ∼1.2% L0 and it was shorter at lower velocities. At a given shortening velocity and over the temperature range of 8–30°C, the rate of T-jump tension rise increased with warming ( Q10≈ 2.7), similar to phase 2b (endothermic force generation) in isometric muscle. Results are discussed in relation to the previous findings in isometric muscle fibres which showed that a T-jump promotes an early step in the crossbridge–ATPase cycle that generates force. In general, the finding that the T-jump effect on active muscle tension is pronounced during shortening, but is depressed/inhibited during lengthening, is consistent with the expectations from the Fenn effect that energy liberation (and acto-myosin ATPase rate) in muscle are increased during shortening and depressed/inhibited during lengthening. [ABSTRACT FROM AUTHOR]

GROWEST PLUS is a software interface, designed to run a new version of the GROWEST plant growth index simulation model, originally developed by Fitzpatrick and Nix in 1970. The GROWEST model was designed to integrate the major climatic determinants of potential plant growth at broad geographic scales, and GROWEST PLUS allows comparisons of current conditions relative to historical variability. Substantive literature demonstrates the robustness, simplicity and application of GROWEST at regional to national scales. This has led the Bureau of Rural Sciences (BRS) to use this tool as one of a suite of analyses and models in the assessment of Exceptional Circumstances drought applications. The advantage of GROWEST is its simplicity. The model synthesises well established biological responses to seasonal trends in climate. It has the advantage of few dimensions, which significantly reduces computational and processing time. GROWEST performs well with the SGS Pasture Model outputs. In fact, GROWEST''s performance is encouraging given the level of simplicity in the model. GROWEST, however, trades off some processes that are important at detailed scales in order to be able to run with readily available input variables for regional scale assessments. Unaccounted processes include detailed simulation of soil moisture, soil fertility and differences between phenological responses at the plant species level. GROWEST PLUS was developed by BRS and the Centre for Resource and Environmental Studies at the Australian National University. The most significant feature of GROWEST PLUS is its ability to analyse variability in seasonal growth over time using time-series outputs from the GROWEST model. For this purpose, the GROWEST model was comprehensively upgraded to run on weekly and monthly climate data, in point or grid form, to produce weekly and monthly outputs. This will have benefit in the analyses of specific events such as drought or the characterisation of growing season reliability for natural resource management. This paper demonstrates how users can easily and intuitively run the upgraded GROWEST model through the GROWEST PLUS graphical user interface, utilising ‘real time’ climate data, in point or grid form, to undertake a range of spatial and temporal analyses. [Copyright &y& Elsevier]

Understanding the nature of the interaction of the plant alkaloid ryanodine with its receptor channel (RyR) is important to aid interpretation of physiological studies and provide structure-function information about RyR. We present here the first quantitative description of the relative single-channel kinetic effects of a single-point mutation in RyR2. We exploit the well-characterized ryanoid 8β-amino-9α-hydroxyryanodine that displays reversible kinetics with RyR2. We explicitly show that the effect of the Q4863A mutation is to increase the apparent dissociation constant by increasing the apparent dissociation rate of the ryanoid. The voltage-dependence of the interaction displays no change. We infer that Q4863 is not involved with the voltage-drop but is able to influence ryanoid-bound structural changes. We discuss structural mechanisms by which this mutation could affect ryanoid interaction. [ABSTRACT FROM AUTHOR]

Knotting of intravascular catheters is an uncommon but a well-recognized occurrence. The Swan–Ganz catheter (SGC) is the one that knots most commonly. A case of a knotted SGC is described in a patient with a persistent left-sided superior vena cava, and we propose that the presence of a left-sided superior vena cava is a risk factor for knot formation not previously reported. We review the published work on the risk factors for knot formation and on the techniques used to remove knotted SGC. We describe a technique using a gooseneck snare and Omni Flush catheter (Angiodynamics, Queensbury, NY, USA) to loosen and untie a knotted SGC. [ABSTRACT FROM AUTHOR]

Lengthening of active muscle is an essential feature of animal locomotion, but the molecular processes occurring are incompletely understood. We therefore examined and modelled tension responses to ramp stretches (5% fibre length, L0) over a wide range of velocities (0.1–10 L0 s−1) of tetanized intact rat muscle fibre bundles ( L0∼2 mm) with a resting sarcomere length of 2.5 μm at 20°C. Tension rose to a peak during stretch and decayed afterwards to a level which was higher than the prestretch tetanic tension. This residual force enhancement was insensitive to velocity. The tension rise during stretch showed an early transition (often appearing as an inflection) at ∼1 ms. Both the stretch ( L1) and the tension rise at this transition increased in proportion to velocity. A second transition, marked by a reduction in slope, occurred at a stretch of ∼18 nm per half-sarcomere; the rise in tension at this transition increased with velocity towards a plateau. Based on analyses of the velocity dependence of the tension and modelling, we propose that the initial steep increase in tension arises from increasing strain of all attached crossbridges and that the first transition reflects the tension loss due to the original post-stroke heads executing a reverse power stroke. Modelling indicates that the reduction in slope at the second transition occurs when the last of the heads that were attached at the start of the ramp become detached. Thereafter, the crossbridge cycle is largely truncated, with prepower stroke crossbridges rapidly detaching at high strain and attaching at low strain, the tension being borne mainly by the prestroke heads. Analysis of the tension decay after the ramp and the velocity dependence of the peak tension suggest that a non-crossbridge component increasingly develops tension throughout the stretch; this decays only slowly, reaching at 500 ms after the ramp ∼20% of its peak value. This is supported by the finding that, in the presence of 10 μm N-benzyl- p-toluene sulphonamide (a myosin inhibitor), while isometric tension is reduced to ∼15%, and the crossbridge contribution to stretch-induced tension rise is reduced to 30–40%, the peak non-crossbridge contribution and the residual force enhancement remain high. We propose that the residual force enhancement is due to changes upon activation in parallel elastic elements, specifically that titin stiffens and C-protein–actin interactions may be recruited. [ABSTRACT FROM AUTHOR]

The suitability of large-fruited apple cultivars as alternative donors of powdery mildew resistance to the crabapples carrying major gene resistances was assessed. Five accessions with varying levels of mildew resistance (‘Dülmener Rosen', ‘Liberty', ‘Sciros', ‘Prima' and ‘Red Delicious') and one susceptible cultivar (‘Cox's Orange Pippin') were mated in a partial diallel design, and sub-sets of each seedling family were evaluated for three years at three New Zealand sites (Havelock North, Riwaka and Clyde) with different climatic conditions. There was a high correlation among the powdery mildew susceptibility scores of the individual seedlings over the three years, but disease levels varied among sites, with those at Clyde being the highest. All accessions with some resistance were found to confer additive resistance to their progenies to varying degrees depending on the climatic conditions of the sites, but findings suggest that progeny selection at Clyde will be sufficient for breeding purposes. The performance of the cultivar itself was not necessarily a good predictor of the level of resistance conferred to its progenies. The mostly negative genetic correlations between powdery mildew scores and fruit quality attributes suggest that selecting for powdery mildew resistance and desirable fruit quality traits may not be difficult. However, a larger number of families may be needed for more precise estimates of the genetic correlations to strengthen confidence in this conclusion. [ABSTRACT FROM AUTHOR]

Background: Dengue is the most important mosquito borne viral infection in the world. Nearly 90% of infections occur in children. At present, prospective information on clinical and laboratory findings in South Asian children with dengue is generally lacking. Aim: To describe patterns of clinical disease in a cohort of children hospitalised with dengue during a major dengue epidemic in Sri Lanka. Results: A total of 104 children were studied during a three month period. Eighteen had dengue fever (DF) and 86 had dengue haemorrhagic fever (DHF). Of those with DHF, 34, 23, 27, and 2 had DHF grade I, II, III, and IV respectively. Based on dengue serology testing, 13 of the DF patients had a primary infection and 5 had secondary dengue infections. In contrast, 68 of the children with DHF had secondary and 18 had primary dengue infections. Oral candidiasis was seen in 19 children. The odds ratio for children with secondary dengue infection to develop DHF was 9.8 (95% CI 3.1 to 31.2). Conclusion: Studies on patterns of paediatric dengue disease in different regions should help clinicians and health administrators make more informed and evidence based health planning decisions. It should also help towards mapping out dengue trends on a global scale. Oral candidiasis has not been previously documented in children suffering with acute dengue in Sri Lanka or elsewhere. Studying underlying reasons for this manifestation during future dengue epidemics may provide useful leads in understanding overall dengue pathogenesis. [ABSTRACT FROM AUTHOR]