Pseudopeptides with a centrally positioned alkene-based disulphide bridge mimetic stimulate kallikrein-related peptidase 3 activity

Peer reviewe

Mesoscale productivity fronts and local fishing opportunities in the European Seas

This study evaluates the relationship between both commercial and scientific spatial fisheries data and a new satellite-based estimate of potential fish production (Ocean Productivity available to Fish, OPFish) in the European Seas. To construct OPFish, we used productivity frontal features derived from chlorophyll-a horizontal gradients, which characterize 10%–20% of the global phytoplankton production that effectively fuels higher trophic levels. OPFish is relatively consistent with the spatial distribution of both pelagic and demersal fish landings and catches per unit of effort (LPUEs and CPUEs, respectively). An index of harvest relative to ocean productivity (HP index) is calculated by dividing these LPUEs or CPUEs with OPFish. The HP index reflects the intensity of fishing by gear type with regard to local fish production. Low HP levels indicate lower LPUEs or CPUEs than expected from oceanic production, suggesting over-exploitation, while high HP levels imply more sustainable fishing. HP allows comparing the production-dependent suitability of local fishing intensities. Our results from bottom trawl data highlight that over-exploitation of demersal species from the shelves is twice as high in the Mediterranean Sea than in the North-East Atlantic. The estimate of HP index by dominant pelagic and demersal gears suggests that midwater and bottom otter trawls are associated with the lowest and highest overfishing, respectively. The contrasts of fishing intensity at local scales captured by the HP index suggest that accounting for the local potential fish production can promote fisheries sustainability in the context of ecosystem-based fisheries management as required by international marine policies

A numerical modelling and simulation of core-scale sandstone acidizing process: a study on the effect of temperature

A wide and comprehensive understanding of the chemical reactions and mechanisms of HBF4 is crucial as it significantly influences its performance in stimulating a sandstone formation. In general, it is well-known that HBF4 is able to provide a deeper penetration into the sandstone matrix before being spent due to its uniquely slow hydrolysis ability to produce HF. In the present study, a 3D numerical modelling and simulation were conducted to examine the capability of HBF4 in enhancing the porosity and permeability of the sandstone matrix. The model is built in COMSOL® Multiphysics commercial software of computational fluid dynamics (CFD) to simulate the acid core flooding process on sandstone core. The model had been validated against the experimental data in the literature. The results matched with the measured plot data very well. The effect of temperature on the performance HBF4 sandstone acidizing is evaluated in this study. The simulation results indicated that at low temperature of 25 °C, HBF4 is not very effective, as justified in its poor porosity and permeability increments of only 1.07 and 1.23, respectively. However, at elevated temperatures, the porosity and permeability enhancement also become increasingly more significant, which showed 1.26 and 2.06, respectively, at 65 °C; and 1.67 and 7.06, respectively, at 105 °C. Therefore, one can conclude that HBF4 acid treatment performed better at elevated temperatures due to increased hydrolysis rate, which is a governing function in HBF4 sandstone acidizing. Overall, this model had provided a reliable alternative to optimize various other parameters of HBF4 acid treatment

Immune cell contexture in the bone marrow tumor microenvironment impacts therapy response in CML

Increasing evidence suggests that the immune system affects prognosis of chronic myeloid leukemia (CML), but the detailed immunological composition of the leukemia bone marrow (BM) microenvironment is unknown. We aimed to characterize the immune landscape of the CML BM and predict the current treatment goal of tyrosine kinase inhibitor (TKI) therapy, molecular remission 4.0 (MR4.0). Using multiplex immunohistochemistry (mIHC) and automated image analysis, we studied BM tissues of CML patients (n = 56) and controls (n = 14) with a total of 30 immunophenotype markers essential in cancer immunology. CML patients' CD4+ and CD8+ T-cells expressed higher levels of putative exhaustion markers PD1, TIM3, and CTLA4 when compared to control. PD1 expression was higher in BM compared to paired peripheral blood (PB) samples, and decreased during TKI therapy. By combining clinical parameters and immune profiles, low CD4+ T-cell proportion, high proportion of PD1+ TIM3-CD8+ T cells, and high PB neutrophil count were most predictive of lower MR4.0 likelihood. Low CD4+ T-cell proportion and high PB neutrophil counts predicted MR4.0 also in a validation cohort (n = 52) analyzed with flow cytometry. In summary, the CML BM is characterized by immune suppression and immune biomarkers predicted MR4.0, thus warranting further testing of immunomodulatory drugs in CML treatment.Peer reviewe

Immune cell constitution in bone marrow microenvironment predicts outcome in adult ALL

As novel immunological treatments are gaining a foothold in the treatment of acute lymphoblastic leukemia (ALL), it is elemental to examine ALL immunobiology in more detail. We used multiplexed immunohistochemistry (mIHC) to study the immune contexture in adult precursor B cell ALL bone marrow (BM). In addition, we developed a multivariate risk prediction model that stratified a poor survival group based on clinical parameters and mIHC data. We analyzed BM biopsy samples of ALL patients (n = 52) and healthy controls (n = 14) using mIHC with 30 different immunophenotype markers and computerized image analysis. In ALL BM, the proportions of M1-like macrophages, granzyme B+CD57+CD8+ T cells, and CD27+ T cells were decreased, whereas the proportions of myeloid-derived suppressor cells and M2-like macrophages were increased. Also, the expression of checkpoint molecules PD1 and CTLA4 was elevated. In the multivariate model, age, platelet count, and the proportion of PD1+TIM3+ double-positive CD4+ T cells differentiated a poor survival group. These results were validated by flow cytometry in a separate cohort (n = 31). In conclusion, the immune cell contexture in ALL BM differs from healthy controls. CD4+PD1+TIM3+ T cells were independent predictors of poor outcome in our multivariate risk model, suggesting that PD1 might serve as an attractive immuno-oncological target in B-ALL.Peer reviewe

Hyperprolactinaemia does not always mean 'hyperprolactinaemia'!

The presence of macroprolactinaemia was investigated in the symptom-free hyperprolactinaemia cases to reveal its incidence. The serum prolactin (PRL) fractions in 21 female patients with hyperprolactinaemia without any clinical symptoms were analyzed with PEG (polyethylene glycol precipitation) procedure. In 14 of these 21 cases, hyperprolactinaemia was detected with a high fraction of macroprolactin. In cases with asymptomatic hyperprolactinaemia, it is more appropriate to employ the PEG precipitation test to detect the disorder. High levels of serum prolactin, do not essentially indicate the presence of a prolactinoma but may only indicate macroprolactinaemia. (C) 2004 Elsevier Ireland Ltd. All rights reserved

OCULAR INVOLVEMENT IN 2 SYMPTOMATIC CONGENITAL ERYTHROPOIETIC PORPHYRIA

Congenital erythropoietic porphyria (Gunther disease, CEP) is a rare autosomal recessive disorder of haeme biosynthesis. It is characterized by extreme photosensitivity and the excretion of large amounts of uroporphyrin I and coproporphyrin I in the urine and coproporphyrin I in the faeces. We have diagnosed two cases of congenital erythropoietic porphyria, who were first cousins once removed. They had recurrent skin bullae, scarring on the face and hands, hirsutism, discoloured fluorescent teeth, red urine, increased haemolysis and grossly increased excretion of porphyrin. Both children had blepharitis and their sclera gave pink fluorescence under long wave ultraviolet light, mainly in the interpalpebral fissures. All the features of our two patients, except the ocular lesions, conformed to cases of CEP reported in the literature. We have encountered no other reports on ocular lesions in CEP since first described by Chumbley in 1977