Miracle-dz/UniFAR-FTUs huggingface dataset:
Environmental life cycle assessment of agricultural systems : integration in decision-making

Environmental Life Cycle Assessment (LCA) is an approach for assessing the comprehensive environmental impacts of human activities; effects are quantified along the life cycle from extraction of raw materials, through processing, manufacturing, transportation, use and on to final disposal. LCA was developed for assessing industrial systems, and agricultural systems are sufficiently different that this area of application introduces new methodological issues for all phases of LCA. These issues are addressed in the thesis; additionally, it explores issues related to the wider use of LCA in decision-making. New methods are presented for assessing use of solar energy and water, soil quantity and quality, and biodiversity. Use of solar energy is assessed in relation to total incident radiation, and use of water in relation to average annual rainfall reaching land in a system under analysis. Soil quantity and quality are assessed assuming that soil is an ancillary item in LCA; this requires careful modelling, use of Organic Matter and Soil Compaction Indicators, and inclusion of eroded soil in assessing abiotic resource depletion. A method for assessing physical habitat maintenance and change is presented which highlights some generic features of LCA mitigating against its acceptance among some stakeholders. A case study of breadmaking wheat production demonstrates practical application of the methods. This suggests it may be equally, or even more, relevant to determine preferred locations of production rather than preferred farming practices in seeking to maximise the environmental performance of agricultural systems. More attention is needed to ensuring the usefulness of LCA results. They should be accurate, relevant, understandable and meaningful to stakeholders, and the LCA approach must be accepted as a legitimate form of analysis. This requires more flexibility in LCA methodology to adapt it to different decision-making contexts, balanced by a greater focus on the process of undertaking LCA.
Nerve growth factor regulates nociception in human health and disease.

In this review, evidence is marshalled for the hypothesis that nerve growth factor (NGF) regulates nociception in human health and disease. The data from humans complement the studies of NGF in animal inflammatory pain models described elsewhere in this issue. An attempt is made to unify the role of NGF in inflammatory and neuropathic hyperalgesia. Although largely speculative at this stage, human conditions are discussed that may present with pain related to alterations of NGF activity—these may provide suitable models for the study of mechanisms of NGF and pain in humans, and new NGF-related prophylaxis and therapies. The “hyperalgesic” conditions include arthritis, some small fibre neuropathies, painful hypertrophic scars, sunburn, urinary bladder pain, migraine and vascular head pain. The “hypoalgesic” group includes leprosy neuropathy. Other conditions, including the major neuropathies that occur after trauma and diabetes, are more complicated and may display different NGF-related features during their development. A neurotrophic factor may be defined as an endogenous substance that plays a role in the development, maintenance or regeneration of the nervous system. Trophic factors act via their highaffinity receptors on specific nerve cells to influence their survival and gene expression. Recent studies have identified a number of neurotrophic factors which play specific roles in the development, maintenance and regeneration of subpopulations of peripheral nerve fibres [24, 39]. The classic neurotrophic factor, NGF, is a protein normally produced by cells in the target organs, such as skin, blood vessels and the bladder; the NGF is secreted, then taken up by sympathetic and small sensory fibres via a high-affinity receptor (trkA), and transported retrogradely to the cell body [2]. In adults,GF is necessary fo r the survivalf sympathetic fibres, and for phenotypic properties of small sensory fibres, such as expression of neuropeptide substance P and capsaicin sensitivity [40, 43, 63]. NGF also has paracrine actions—for example, it
Development and Validation of a Stability-indicating UV Spectroscopic Method for Candesartan in Bulk and Formulations

A simple, specific, accurate and stability-indicating UV- Spectrophotometric method was developed for the estimation of candesartan cilexitil, using a Shimadzu, model 1700 spectrophotometer and a mobile phase composed of methanol: water in the ratio of 9:1 at wave length (λmax) 254 nm. Linearity was established for candesartan in the range of 10-90 μg/ml. The percentage recovery of was found to be in the range of 99.76-100.79%. The drug was subjected to acid, alkali and neutral hydrolysis, oxidation, dry heat, UV light and photolytic degradation. Validation experiments performed to demonstrate system suitability, specificity, precision, linearity, accuracy, interday assay, intraday assay, robustness, ruggedness, LOD, and LOQ. While estimating the commercial formulation there was no interference of excipients and other additives. Hence this method can be used for routine determination of candesartan cilexetil in bulk and their pharmaceutical dosage forms. The proposed method for stability study shows that there was appreciable degradation found in stress condition of candesartan.
Targeting Vascular Endothelial Growth Factor Receptor in Thyroid Cancer: The Intracellular and Extracellular Implications

Our understanding of the molecular pathophysiology of differentiated thyroid cancer (DTC) has developed considerably over the last 10 years. Aberrant signaling through B-Raf and Akt has been implicated in the tumorigenesis of DTC. Moreover, these highly vascular tumors have proven to be sensitive to the inhibition of vascular endothelial growth factor receptor (VEGFR-2). It is likely that the multikinase inhibitors, sorafenib, sunitinib, axitinib, and motesanib, whose targets include VEGFR-2, exert their effects primarily through inhibition of endothelial cells. However, as VEGFR-2 is expressed on DTC cells, these compounds may have direct antitumor action. This review will discuss the key signaling pathways involved in thyroid cancer and their implications for targeted therapy. Clin Cancer Res; 16(3); 778–83
How Costly is Financial (Not Economic) Distress? Evidence from Highly Leveraged Transactions that Became Distressed

This paper studies thirty-one highly leveraged transactions (HLTs) that become financially, not economically, distressed. The net effect of the HLT and financial distress (from pretransaction to distress resolution, market- or industry-adjusted) is to increase value slightly. This finding strongly suggests that, overall, the HLTs of the late 1980s created value. We present quantitative and qualitative estimates of the (direct and indirect) costs of financial distress and their determinants. We estimate financial distress costs to be 10 to 20 percent of firm value. For a subset of firms that do not experience an adverse economic shock, financial distress costs are negligible. Copyright The American Finance Association 1998.
Nonadherence Increases the Risk of Hospitalization Among HIV-Infected Antiretroviral Naïve Patients Started on HAART

Background. Since the advent of highly active antiretroviral therapy (HAART), AIDS-related hospitalizations have decreased. The objective of this study was to assess the impact of adherence on hospitalization among antiretroviral-naïve HIV-infected persons initiating HAART. Methods. Analysis was based on a cohort of individuals initiating HAART between 1996 and 2001. The primary outcome was hospitalization for one or more days. Survival methods were used to assess the impact of adherence on hospitalization. Results. Of 1605 eligible participants, 672 (42%) were hospitalized for one or more days after initiating HAART. Median adherence levels were 92 (IQR: 58, 100) and 100 (IQR: 83, 100) among those ever and never hospitalized, respectively. After controlling for confounders, those with <95% adherence had 1.88 times (95% CI: 1.60, 2.21) higher risk for hospitalization. Conclusions. Suboptimal adherence among HIV-infected patients taking HAART predicts hospitalization. Identifying and addressing factors contributing to poor adherence early in treatment could improve patient care and lower hospitalization costs.
equivalence in birational geometry and characterizations of complex elliptic genera

We show that for smooth complex projective varieties the most general combinations of chern numbers that are invariant under the K-equivalence relation consist of the complex elliptic genera. Combined with a recent result of Totaro, we deduce that up to complex cobordism any K-equivalence can be decomposed into a sequence of classical flops.
Zebrafish Embryo as an In Vivo Model for Behavioral and Pharmacological Characterization of Methylxanthine Drugs

Zebrafish embryo is emerging as an important tool for behavior analysis as well as toxicity testing. In this study, we compared the effect of nine different methylxanthine drugs using zebrafish embryo as a model. We performed behavioral analysis, biochemical assay and Fish Embryo Toxicity (FET) test in zebrafish embryos after treatment with methylxanthines. Each drug appeared to behave in different ways and showed a distinct pattern of results. Embryos treated with seven out of nine methylxanthines exhibited epileptic-like pattern of movements, the severity of which varied with drugs and doses used. Cyclic AMP measurement showed that, despite of a significant increase in cAMP with some compounds, it was unrelated to the observed movement behavior changes. FET test showed a different pattern of toxicity with different methylxanthines. Each drug could be distinguished from the other based on its effect on mortality, morphological defects and teratogenic effects. In addition, there was a strong positive correlation between the toxic doses (TC50) calculated in zebrafish embryos and lethal doses (LD50) in rodents obtained from TOXNET database. Taken together, all these findings elucidate the potentiality of zebrafish embryos as an in vivo model for behavioral and toxicity testing of methylxanthines and other related compounds.
Water diffusion into and electrical testing of composite insulator GRP rods

This paper describes water diffusion into and electrical testing of unidirectional glass reinforced polymer (GRP) composite rods used as load bearing components in high voltage composite (non-ceramic) insulators. The tests were performed following ANSI standard C29.11 Section 7.4. 2 that can be used to evaluate electrical properties of composites. The unidirectional composite rod materials based on either E-glass or ECR-glass fibers with modified polyester, epoxy and vinyl ester resins were investigated. Two types of ECR-glass fibers were considered, namely high and low seed (voids). The effects of composite surface sandblasting, mechanical pre-loading and nitric acid exposure on the electrical properties of the composites were studied. In addition to the required data of the ANSI standard, the specimen mass gain was also measured after boiling for 100 h. Most importantly, there was no correlation found between the mass gain and the leakage current for different composites. The materials with high seed ECR-glass fibers had much higher leakage currents and they absorbed less moisture than the composites based on either the low seed ECR-glass fibers or E-glass fibers. It was shown in this work that different types of sandblasting, as well as mechanical preloading with and without acid exposure had a negligible effect on the leakage currents and water mass gain of the composite specimens.
In situ studies of renal arteriolar function using the in vitro-perfused hydronephrotic rat kidney.

A method of examining arteriolar function in situ using the in vitro-perfused hydronephrotic rat kidney is described. This approach facilitates direct visualization of arteriolar contractile responses in a well-controlled experimental environment while avoiding the consequences of traumatic microdissection and the accompanying exposure to ischemia, hypothermia, or hypoxia. The preparation has a remarkably well-preserved myogenic reactivity, exhibiting precisely graded vasoconstriction over the range in perfusion pressure subtending normal renal autoregulatory responses (i.e., 80-180 mm Hg). Using this preparation, the inhibitory effects of hypoxia on arteriolar myogenic reactivity have been demonstrated. The range over which reduced pO2 affected arteriolar reactivity in this model corresponded closely to that reported to alter vascular tone in vivo. A technique of adapting the model to incorporate simultaneous monitoring of arteriolar fluorescence measurements and contractile responses is also described. This approach has been used to examine the relationship between arteriolar contractility and NADH autofluorescence during the hypoxia-induced activation of ATP-sensitive K channels. Future applications may include the use of intravital fluorescent dyes to examine, for example, microvascular endothelial calcium signaling in an intact, functioning arteriole.
Simple and powerful instrument model for the source separation of polyphonic music

This article presents a new approach to sound source separation. The introduced algorithm is based on spectral modeling of real instruments. The separation of independent sources is carried out by dividing the energy of the mixture signal based on these instrument models. This way it is possible to regain some of the information that was lost when the independent sources were mixed together into a single signal. The paper presents the theory behind the proposed separation system, then focuses on the instrument model that is the basic element of the approach. Measurement results are given for polyphony levels from 2 to 10 demonstrating the separation quality, with special regard to the effect of prints on the result.
In Vitro Characterization of GSK2485852, a Novel Hepatitis C Virus Polymerase Inhibitor

ABSTRACT GSK2485852 (referred to here as GSK5852) is a hepatitis C virus (HCV) NS5B polymerase inhibitor with 50% effective concentrations (EC50s) in the low nanomolar range in the genotype 1 and 2 subgenomic replicon system as well as the infectious HCV cell culture system. We have characterized the antiviral activity of GSK5852 using chimeric replicon systems with NS5B genes from additional genotypes as well as NS5B sequences from clinical isolates of patients infected with HCV of genotypes 1a and 1b. The inhibitory activity of GSK5852 remained unchanged in these intergenotypic and intragenotypic replicon systems. GSK5852 furthermore displays an excellent resistance profile and shows a <5-fold potency loss across the clinically important NS5B resistance mutations P495L, M423T, C316Y, and Y448H. Testing of a diverse mutant panel also revealed a lack of cross-resistance against known resistance mutations in other viral proteins. Data from both the newer 454 sequencing method and traditional population sequencing showed a pattern of mutations arising in the NS5B RNA-dependent RNA polymerase in replicon cells exposed to GSK5852. GSK5852 was more potent than HCV-796, an earlier inhibitor in this class, and showed greater reductions in HCV RNA during long-term treatment of replicons. GSK5852 is similar to HCV-796 in its activity against multiple genotypes, but its superior resistance profile suggests that it could be an attractive component of an all-oral regimen for treating HCV.
Reendothelialization of human heart valve neoscaffolds using umbilical cord-derived endothelial cells.

BACKGROUND Heart valve tissue engineering represents a concept for improving the current methods of valvular heart disease therapy. The aim of this study was to develop tissue engineered heart valves combining human umbilical vein endothelial cells (HUVECs) and decellularized human heart valve matrices. METHODS AND RESULTS Pulmonary (n=9) and aortic (n=6) human allografts were harvested from explanted hearts from heart transplant recipients and were decellularized using a detergent-based cell extraction method. Analysis of decellularization success was performed with light microscopy, transmission electron microscopy and quantitative analysis of collagen and elastin content. The decellularization method resulted in full removal of native cells while the mechanical stability and the quantitative composition of the neoscaffolds was maintained. The luminal surface of the human matrix could be successfully recellularized with in vitro expanded HUVECs under dynamic flow conditions. The surface appeared as a confluent cell monolayer of positively labeled cells for von Willebrand factor and CD 31, indicating their endothelial nature. CONCLUSIONS Human heart valves can be decellularized by the described method. Recellularization of the human matrix resulted in the formation of a confluent HUVEC monolayer. The in vitro construction of tissue-engineered heart valves based on decellularized human matrices followed by endothelialization using HUVECs is a feasible and safe method, leading to the development of future clinical strategies in the treatment of heart valve disease.
Mechanism and Function of Drosophila capa GPCR: A Desiccation Stress-Responsive Receptor with Functional Homology to Human NeuromedinU Receptor

The capa peptide receptor, capaR (CG14575), is a G-protein coupled receptor (GPCR) for the D. melanogaster capa neuropeptides, Drm-capa-1 and -2 (capa-1 and -2). To date, the capa peptide family constitutes the only known nitridergic peptides in insects, so the mechanisms and physiological function of ligand-receptor signalling of this peptide family are of interest. Capa peptide induces calcium signaling via capaR with EC50 values for capa-1 = 3.06 nM and capa-2 = 4.32 nM. capaR undergoes rapid desensitization, with internalization via a b-arrestin-2 mediated mechanism but is rapidly re-sensitized in the absence of capa-1. Drosophila capa peptides have a C-terminal -FPRXamide motif and insect-PRXamide peptides are evolutionarily related to vertebrate peptide neuromedinU (NMU). Potential agonist effects of human NMU-25 and the insect -PRLamides [Drosophila pyrokinins Drm-PK-1 (capa-3), Drm-PK-2 and hugin-gamma [hugg]] against capaR were investigated. NMU-25, but not hugg nor Drm-PK-2, increases intracellular calcium ([Ca2+]i) levels via capaR. In vivo, NMU-25 increases [Ca2+]i and fluid transport by the Drosophila Malpighian (renal) tubule. Ectopic expression of human NMU receptor 2 in tubules of transgenic flies results in increased [Ca2+]i and fluid transport. Finally, anti-porcine NMU-8 staining of larval CNS shows that the most highly immunoreactive cells are capa-producing neurons. These structural and functional data suggest that vertebrate NMU is a putative functional homolog of Drm-capa-1 and -2. capaR is almost exclusively expressed in tubule principal cells; cell-specific targeted capaR RNAi significantly reduces capa-1 stimulated [Ca2+]i and fluid transport. Adult capaR RNAi transgenic flies also display resistance to desiccation. Thus, capaR acts in the key fluid-transporting tissue to regulate responses to desiccation stress in the fly.
Alternative modes of binding of proteins with tandem SH2 domains

The issue of specificity in tyrosine kinase intracellular signaling mediated by src homology 2 (SH2) domains has great importance in the understanding how individual signals maintain their mutual exclusivity and affect downstream responses. Several proteins contain tandem SH2 domains that, on interacting with their ligand, provide a higher level of specificity than can be afforded by the interaction of a single SH2 domain. In this study, we focus on the comparison of two proteins ZAP70 and the p85 subunit of PI 3‐kinase, which although distinctly different in function and general structure, possess tandem SH2 domains separated by a linker region and which bind to phosphorylated receptor molecules localized to the cell membrane. Binding studies using isothermal titration calorimetry show that these two proteins interact with peptides mimicking their physiological ligands in very different ways. In the case of the SH2 domains from ZAP70, they interact with a stoichiometry of unity, while p85 is able to make two distinct interactions, one with a stoichiometry of 1:1 and the other with two p85 molecules interacting with one receptor. The observation of two different modes of binding of p85 might be important in providing different cellular responses based on fluctuating intracellular concentration regimes of this protein. Thermodynamic data on both proteins suggest that a conformational change occurs on binding. On investigation of this structural change using a truncated form of p85 (including just the two SH2 domains and the inter‐SH2 region), both NMR and circular dichroism spectroscopic studies failed to show significant changes in secondary structure. This suggests that any conformational change associated with binding is small and potentially limited to loop regions of the protein.
A Cautionary Note Regarding the Use of Cumulative Burnt Areas for the Determination of Fire Danger Index Breakpoints

Identifying the links between fire danger metrics and fire activity is critical in various operational and research fields. A common methodology consists in analysing the relationship between cumulative burnt areas and fire danger metrics. Building on this approach, it has been proposed that fuel moisture content (FMC) drives fire activity in some ecosystems through between one and three breakpoints corresponding to the onset or saturation of fire activity. We demonstrate, through two different approaches, that this methodology is incorrect, because it is biased by the frequency distribution of FMC values. From comparison with a neutral fire distribution and correction for the frequency bias, we show that cumulative burnt area breakpoints are spurious: an upper breakpoint might exist (but would be higher than expected), while no evidence of reduced fire danger was detected for the lowest values of FMC (on the contrary, a secondary increase was detected). Our findings clearly suggest that previous breakpoints resulting from this methodology should be considered with caution, as erroneous conclusions regarding fire danger breakpoints could have major consequences for both fire safety and science outcomes. Finally, we discuss widespread confusion between fire danger breakpoints and fire danger levels, which explains most previous erroneous conclusions.
South Asian Children Have Increased Body Fat in Comparison to White Children at the Same Body Mass Index

The ability of body mass index (BMI) to predict excess fat in South Asian children is unknown. This cross-sectional study examines the influence of ethnicity on body fatness in children. Weight status and body fat were determined using BMI, waist circumference (WC), two skinfold sites (SF; triceps and subscapula) and leg-to-leg bioelectrical impedance analysis (BIA; Tanita BF350, Tanita, Tokyo, Japan) in 194 children aged 8.47 ± 0.50 years from Coventry, United Kingdom. Biological maturity was also determined. Analysis of covariance (ANCOVA) identified significant differences between ethnic (p < 0.001) and gender groups’ BMI (p = 0.026), with a significant covariate for skinfold (p < 0.001) and bioelectrical impedance (p < 0.001). For a given body fat value, South Asian children and females had a lower BMI value (−1.12 kg/m2, p < 0.001 and −0.50 kg/m2, p = 0.026, respectively, when adjusted for SF; −1.56 kg/m2, p < 0.001 and −0.31 kg/m2, p = 0.16, respectively, when adjusted for BIA) compared with white children and boys. The prediction model including ethnicity, gender and BIA explained 80.4% of the variance in BMI. Maturation was not found to be a significant covariate (p > 0.05). To conclude, the findings suggest that BMI cut-points may need to be lowered in South Asian children, and thus age-by-sex-by-ethnicity specific BMI cut-points are needed in children. Further research examining body composition with health parameters in this population is needed.