Hydrophilic networks based on functionalized hyaluronic acid and on partially acetylated chitosan, respectively, have been obtained. In the case of hyaluronic acid (HA), primary amino functionalities ...have been introduced along the polysaccharide chains. The ensuing derivatives, i.e., HA-lysine (HA-K), HA-diamino pentane (HA-DAP), and HA-glycine-lysine (HA-GK), have been characterized by high field NMR spectroscopy. NMR 2D-DOSY experiments have allowed us to optimize the purification procedure. Chitosan was made soluble in water by partial acetylation. Cross-linking reactions have been performed using glutaraldehyde. The obtained networks have been qualitatively characterized by means of 13C CP-MAS NMR technique. The hydrogels have been characterized also in terms of water uptake.
The synthesis of potassium 3-sulfopropyl methacrylate (SPMA) homopolymers and amphiphilic block copolymers with methyl methacrylate (MMA) by ATRP in water/DMF mixed solvent at 20 °C using a ...Cu/bipyridine catalyst and halogen exchange is described. SPMA homopolymerization in pure water was poorly controlled even when 200% of Cu(II)Cl2 with respect to Cu(I)Cl was added, leading to a relatively high polydispersity (1.38). In water:DMF 50:50 (v/v), addition of at least 60% of Cu(II)Cl2 with respect to Cu(I)Cl allowed to obtain a good control of the polymerization. Linear kinetic plots up to very high conversion were observed and the final polydispersities were relatively low (1.15−1.25). Good self-blocking efficiencies were demonstrated by chain extension experiments even when the first block conversion before the addition of the second feed was very high (>90%). Amphiphilic block copolymers with MMA (number-average degree of polymerization X n,SPMA = 50, X n,MMA = 25) were directly prepared in water:DMF 40:60 (v/v) without using protecting group chemistry or post-polymerization derivatization. The first-order kinetic plot for MMA polymerization was linear up to 96% conversion. Two block copolymers with the same composition, p(SPMA50-b-MMA25)1pot and p(SPMA50-b-MMA25)2pot, were prepared with “one-pot” and “two-pot” procedures. p(SPMA50-b-MMA25)2pot prepared using a purified pSPMA macroinitiator for MMA polymerization gave well-defined core−shell spherical micelles with an average hydrodynamic radius of about 14 nm determined by dynamic light scattering (DLS) measurements. p(SPMA50-b-MMA25)1pot prepared using the sequential monomer addition gave large micellar clusters (more than 100 nm) in addition to simple but smaller micelles. A tentative explanation to the presence of the larger aggregates was given.
This letter details the collective views of a number of independent researchers on the technical assessment and evaluation of environmental models and software. The purpose is to stimulate debate and ...initiate action that leads to an improved quality of model development and evaluation, so increasing the capacity for models to have positive outcomes from their use. As such, we emphasize the relationship between the model evaluation process and credibility with stakeholders (including funding agencies) with a view to ensure continued support for modelling efforts.
Many journals, including EM&S, publish the results of environmental modelling studies and must judge the work and the submitted papers based solely on the material that the authors have chosen to present and on how they present it. There is considerable variation in how this is done with the consequent risk of considerable variation in the quality and usefulness of the resulting publication. Part of the problem is that the review process is reactive, responding to the submitted manuscript. In this letter, we attempt to be proactive and give guidelines for researchers, authors and reviewers as to what constitutes best practice in presenting environmental modelling results. This is a unique contribution to the organisation and practice of model-based research and the communication of its results that will benefit the entire environmental modelling community. For a start, our view is that the community of environmental modellers should have a common vision of minimum standards that an environmental model must meet. A common vision of what a good model should be is expressed in various guidelines on Good Modelling Practice. The guidelines prompt modellers to codify their practice and to be more rigorous in their model testing. Our statement within this letter deals with another aspect of the issue – it prompts professional journals to codify the peer-review process. Introducing a more formalized approach to peer-review may discourage reviewers from accepting invitations to review given the additional time and labour requirements. The burden of proving model credibility is thus shifted to the authors. Here we discuss how to reduce this burden by selecting realistic evaluation criteria and conclude by advocating the use of standardized evaluation tools as this is a key issue that needs to be tackled.
Drying is an important process for the conservation and subsequent marketing of fruits due to their high water activity which makes them highly perishable. Dried products have to meet high quality ...standards, and one of the most important aspects in fruit drying is the need to obtain products with uniform organoleptic properties. Therefore, the knowledge and the optimization of drying process are very important in order to minimize thermal damage and quality loss. In the case of pears, sugar concentrations are relatively high (60–75 g/100 g dry basis) and greatly increase as water evaporates, offering, combined with fruit shrinkage, an additional resistance to moisture transfer from the fruit. In this study, the effect of drying on properties of pear samples (Pyrus Communis ‘Conference’) was analysed. In particular, the water transport mechanism was investigated in pear during drying process at 50 °C. The drying kinetics were obtained by standard weight measurements and the water loss in chosen sample sections (exterior, intermediate and central sections) was evaluated. The drying moisture profiles of samples were also investigated by portable NMR, a non-invasive and non- destructive technique. The water loss obtained by standard weight measurement and the extent of shrinkage obtained by means of a vernier calliper were found to be in a good agreement with the results obtained by portabl
abstract
Streptomyces NRRL 30562 was originally isolated as an endophyte from Kennedia nigriscans, snakevine, in the Northern Territory of Australia. This plant has been used for centuries by ...Aboriginal peoples to treat open bleeding wounds to prevent sepsis. A solvent extract of the crude fluid from cultures of this endophyte possesses wide-spectrum antibiotic activity. Some of the bioactivity is associated with the appearance of actinomycins X2, D, and Xoβ, the first two of which had been previously designated munumbicins A and B, respectively. Other novel compounds bearing wide-spectrum antibiotic activity are also produced by Streptomyces NRRL 30562, and these are designated munumbicins E-4 and E-5. Mass spectrometric analyses of these peptide antibiotics show that they have identical masses (1445.00) but different retention times on HPLC. Both compounds showed activity against gram-positive and gram-negative bacteria. The plant pathogenic fungus, Pythium ultimum is sensitive to both munumbicins at 5.0 μg mL−1 The malarial parasite, Plasmodium falciparum has IC50 values of 0.50±0.08 and 0.87±0.0.26 μg mL−1 for E-4 and E-5, respectively. It appears that other bioactive compounds, related to E-4 and E-5, are also produced making it the most biologically active endophytic Streptomyces spp. on record.
Randomized controlled trials (RCTs) in the field of diabetes have limitations inherent to the fact that design, setting, and patient characteristics may be poorly transferrable to clinical practice. ...Thus, evidence from studies using routinely accumulated clinical data are increasingly valued.
We herein describe rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes), a multicenter retrospective nationwide study conducted at 50 specialist outpatient clinics in Italy and promoted by the Italian Diabetes Society.
The primary objective of the study is to describe the baseline clinical characteristics (particularly HbA1c) of patients initiated on dapagliflozin from marketing authorization approval to the end of 2016. Secondary and exploratory objectives will evaluate the changes in glycaemic and extraglycaemic efficacy parameters after initiation of dapagliflozin or after initiation of comparator glucose lowering medications (DPP-4 inhibitors, gliclazide extended release, and long-acting GLP-1 receptor agonists). An automated software will extract relevant data from the same electronic chart system at all centres, thereby minimizing data treatment and human intervention.
The study is expected to collect an enormous dataset of information on dapagliflozin- and comparator-using patients. After study completion, the Italian Diabetes Society will launch an open crowdsourcing call on the DARWIN-T2D database, challenging diabetes researchers to apply their ideas and approaches to address new unmet needs and knowledge gaps in diabetes. We believe this will move DARWIN-T2D to the next generation of real world studies.
Guar gum, a β-d-(1→4)-linked d-mannan with α-d-galactopyranosyl units attached as side groups, was treated with α-galactosidase, an enzyme that splits off the α-d-galactosyl units to obtain a ...galactomannan with a low galactose content. The galactose-depleted polysaccharide was then selectively oxidized in C(6) position and epimerized using mannuronan C(5)-epimerases, namely AlgE1, AlgE4, AlgE6, and their mixtures, obtaining new pseudo-alginates. In this paper, we report a full high field 1D and 2D NMR study of guar gum as such and of the galactose-depleted, oxidized and epimerized compounds, respectively. From the 1H NMR spectra, the degree of epimerization, the distribution of mannuronic acid (M) and guluronic acid (G) residues and the average G-block length, NG>1, were obtained. By means of NMR diffusion experiments, it was also shown that no significant degradation of the polysaccharide occurs as a consequence of the epimerization reactions.
Background: Over the last two decades several phenotypic, molecular, and chromosomal markers have been identified that are significantly associated with the prognosis of CLL patients. Therefore, ...clinicians managing CLL patients would benefit from a simplified prognostic index.
Methods: We analyzed prospectively collected data from 337 Binet A CLL patients enrolled in Italian the O-CLL1-GISL protocol with the aim of developing scores capable of predicting treatment free survival (TFS). Factors independently associated with TFS were included in the prognostic indexes. To account for differences in the magnitude of the association between the individual independent factors and TFS, we assigned a weighted risk score to each factor based on ranges of their corresponding hazard ratios (HRs) (i.e., 1 point for HR 1.1-1.9; 2 points for HR 2.0-2.9, etc.). The total risk score was then calculated by the sum of the ratings of each factor on individual basis. Risk groups were identified combining risk categories with a non-statistically different TFS.
Results: We developed two scores based on weighted multivariable models: the first included clinical and laboratory parameters clinical score (c-score), while the second was based on biological markers biological score (b-score) (Table 1). The c-score allowed to predict the TFS of patients through the combination of Rai stage, b2-microglobulin and absolute lymphocyte count (ALC), while the b-score predicted TFS by IGHV mutational status and CD38 expression. The c-score showed a C-statistic of 0.72, while the b-score was 0.67, although cases stratified according to the b-score showed a more specific mRNA/microRNA profile. When the two scores were forced in a multivariate analysis, both showed an independent predictive value on TFS with a similar HR, demonstrating their complementarity. Thus, we attempted to integrate the two scores performing a further multivariate analysis in which all parameters, significantly associated with TFS at univariate analysis, were tested (Table 1). ALC, Rai stage, b2-microglobulin together with IGHV mutational status, resulted independently associated with TFS. We constructed a weighted score comprehensive score (co-score), including all the above 4 variables, which allowed the identification of 3 different risk groups with significantly different TFS (Figure 1). The C-statistic of the g-score was 0.75, showing a better concordance than the other two scores. Moreover, its validity was externally validated in a series of 297 newly diagnosed Binet A CLL patients from the Mayo Clinic, USA.
Conclusions: Using this multistep process and external validation, we developed a score with high discriminatory power and predictive significance on the individual patient level.
Table 1Univariate and multivariate Cox proportional Hazards ModelsVariableUnivariate analysisMultivariate analysisClinical modelBiological modelComprehensive modelHR (95% CI)PHR (95% CI)PscoreHR (95% CI)PscoreHR (95% CI)PscoreAge (years) 601.12 (0.73-1.74)0.59---Sex Male/Female0.93 (0.6-1.44)0.93---Rai stage 0/I-II2.30 (1.47-3.50)<0.00012.13 (1.24-3.03)0.0040/2---1.76 (1.11-2.78)0.0150/1ALC (109/L) 103.43 (1.99-5.92)<0.00012.91 (1.85-5.20)<0.00010/2---2.70 (1.54-4.72)0.0010/2b-2 microglobulin normal/elevated3.04 (1.96-4.70)<0.00012.78 (1.79-4.30)<0.00010/2---2.65 (1.66-4.21)<0.00010/2LDH normal/elevated1.25 (0.57-2.71)0.57---CD38 negative/positive3.22 (2.06-5.02)<0.0001---2.11 (1.15-3.16)0.020/21.40 (0.80-2.42)0.24-ZAP-70 negative/positive2.34 (1.51-3.61)<0.0001---1.21 (0.70-2.16)0.485-1.0 (0.98-1.01)0.72-IGHVmutated/unmutated3.57 (2.32-5.50)<0.0001---2.10 (1.12-3.90)0.0190/22.39 (1.27-4.50)0.0070/2FISH risk low+int/high2.93 (1.46-5.90)0.002---1.65 (0.76-3.34)0.216-1.80 (0.84-3.88)0.13-Abbreviations: ALC: absolute lymphocyte count; CI: confidential interval; HR: hazard ratio.
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Shanafelt:Cephalon: Research Funding; Glaxo-Smith-Kline: Research Funding; Genentech: Research Funding; Hospira: Research Funding; Celgene: Research Funding; Jannsen: Research Funding; Polyphenon E International: Research Funding; Pharmacyclics: Research Funding. Kay:Genentech: Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Hospira: Research Funding; Tolero Pharma: Research Funding; Pharmacyclics: Research Funding.
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