Transformation Toughening in Ceramics

The origin of transformation toughening in ceramics is examined using two separate approaches: one based on the stress field ahead of the crack and the other on the changes in thermodynamic potential during a crack increment. Both approaches yield essentially similar predictions of trends in toughness with particle size, temperature, composition, etc. The stress intensity analysis provides fully quantitative predictions of the toughness. These indicate that the shielding of the crack by the transformation zone only develops in the presence of a transformed wake, leading to R-curve behavior

Serum nucleosomes during neoadjuvant chemotherapy in patients with cervical cancer. Predictive and prognostic significance

BACKGROUND: It has been shown that free DNA circulates in serum plasma of patients with cancer and that at least part is present in the form of oligo- and monucleosomes, a marker of cell death. Preliminary data has shown a good correlation between decrease of nucleosomes with response and prognosis. Here, we performed pre- and post-chemotherapy determinations of serum nucleosomes with an enzyme-linked immunosorbent assay (ELISA) method in a group of patients with cervical cancer receiving neoadjuvant chemotherapy. METHODS: From December 2000 to June 2001, 41 patients with cervical cancer staged as FIGO stages IB2-IIIB received three 21-day courses of carboplatin and paclitaxel, both administered at day 1; then, patients underwent radical hysterectomy. Nucleosomes were measured the day before (baseline), at day seven of the first course and day seven of the third course of chemotherapy. Values of nucleosomes were analyzed with regard to pathologic response and to time to progression-free and overall survival. RESULTS: All patients completed chemotherapy, were evaluable for pathologic response, and had nucleosome levels determined. At a mean follow-up of 23 months (range, 7–26 months), projected progression time and overall survival were 80.3 and 80.4%, respectively. Mean differential values of nucleosomes were lower in the third course as compared with the first course (p >0.001). The decrease in the third course correlated with pathologic response (p = 0.041). Survival analysis showed a statistically significant, better progression-free and survival time in patients who showed lower levels at the third course (p = 0.0243 and p = 0.0260, respectively). Cox regression analysis demonstrated that nucleosome increase in the third course increased risk of death to 6.86 (95% confidence interval [CI 95%], 0.84–56.0). CONCLUSION: Serum nucleosomes may have a predictive role for response and prognostic significance in patients with cervical cancer patients treated with neoadjuvant chemotherapy

Promiscuous Aggregate-Based Inhibitors Promote Enzyme Unfolding

One of the leading sources of false positives in early drug discovery is the formation of organic small molecule aggregates, which inhibit enzymes nonspecifically at micromolar concentrations in aqueous solution. The molecular basis for this widespread problem remains hazy. To investigate the mechanism of inhibition at a molecular level, we determined changes in solvent accessibility that occur when an enzyme binds to an aggregate using hydrogen-deuterium exchange mass spectrometry. For AmpC beta-lactamase, binding to aggregates of the small molecule rottlerin increased the deuterium exchange of all 10 reproducibly detectable peptides, which covered 41% of the sequence of beta-lactamase. This suggested a global increase in proton accessibility upon aggregate binding, consistent with denaturation. We then investigated whether enzyme-aggregate complexes were more susceptible to proteolysis than uninhibited enzyme. For five aggregators, trypsin degradation of beta-lactamase increased substantially when beta-lactamase was inhibited by aggregates, whereas uninhibited enzyme was generally stable to digestion. Combined, these results suggest that the mechanism of action of aggregate-based inhibitors proceeds via partial protein unfolding when bound to an aggregate particle

A Biodiverse Rich Environment Does Not Contribute to a Better Diet: A Case Study from DR Congo

The potential of biodiversity to increase and sustain nutrition security is increasingly recognized by the international research community. To date however, dietary assessment studies that have assessed how biodiversity actually contributes to human diets are virtually absent. This study measured the contribution of wild edible plants (WEP) to the dietary quality in the high biodiverse context of DR Congo. The habitual dietary intake was estimated from 2 multiple-pass 24 h dietary recalls for 363 urban and 129 rural women. All WEP were collected during previous ethnobotanical investigations and identified and deposited in the National Botanical Garden of Belgium (BR). Results showed that in a high biodiverse region with precarious food security, WEP are insufficiently consumed to increase nutrition security or dietary adequacy. The highest contribution came from Dacryodes edulis in the village sample contributing 4.8% of total energy intake. Considering the nutrient composition of the many WEP available in the region and known by the indigenous populations, the potential to increase nutrition security is vast. Additional research regarding the dietary contribution of agricultural biodiversity and the nutrient composition of WEP would allow to integrate them into appropriate dietary guidelines for the region and pave the way to domesticate the most interesting WEP

Global Assessment of Functioning (GAF): properties and frontier of current knowledge

ABSTRACT: BACKGROUND: Global Assessment of Functioning (GAF) is well known internationally and widely used for scoring the severity of illness in psychiatry. Problems with GAF show a need for its further development (for example validity and reliability problems). The aim of the present study was to identify gaps in current knowledge about properties of GAF that are of interest for further development. Properties of GAF are defined as characteristic traits or attributes that serve to define GAF (or may have a role to define a future updated GAF). METHODS: A thorough literature search was conducted. RESULTS: A number of gaps in knowledge about the properties of GAF were identified: for example, the current GAF has a continuous scale, but is a continuous or categorical scale better? Scoring is not performed by setting a mark directly on a visual scale, but could this improve scoring? Would new anchor points, including key words and examples, improve GAF (anchor points for symptoms, functioning, positive mental health, prognosis, improvement of generic properties, exclusion criteria for scoring in 10-point intervals, and anchor points at the endpoints of the scale)? Is a change in the number of anchor points and their distribution over the total scale important? Could better instructions for scoring within 10-point intervals improve scoring? Internationally, both single and dual scales for GAF are used, but what is the advantage of having separate symptom and functioning scales? Symptom (GAF-S) and functioning (GAF-F) scales should score different dimensions and still be correlated, but what is the best combination of definitions for GAF-S and GAF-F? For GAF with more than two scales there is limited empirical testing, but what is gained or lost by using more than two scales? CONCLUSIONS: In the history of GAF, its basic properties have undergone limited changes. Problems with GAF may, in part, be due to lack of a research programme testing the effects of different changes in basic properties. Given the widespread use, research-based development of GAF has not been especially strong. Further research could improve GAF

Evidence for long-range glycosyl transfer reactions in the gas phase

AbstractA long-range glycosyl transfer reaction was observed in the collision-induced dissociation Fourier transform (CID FT) mass spectra of benzylamine-labeled and 9-aminofluorene-labeled lacto-N-fucopentaose I (LNFP I) and lacto-N-difucohexaose I (LNDFH I). The transfer reaction was observed for the protonated molecules but not for the sodiated molecules. The long-range glycosyl transfer reaction involved preferentially one of the two L-fucose units in labeled LNDFH I. CID experiments with labeled LNFP I and labeled LNFP II determined the fucose with the greatest propensity for migration. Further experiments were performed to determine the final destination of the migrating fucose. Molecular modeling supported the experiments and reaction mechanisms are proposed