Credit Scorecard for Corporate Clients based on Industries

A mathematical model for an improved credit scorecard is developed. Ideally, this scorecard will not reject "good" clients nor will it approve a loan to "bad" clients

Novel nano-composite hydrogels with honey effective against multi-resistant clinical strains of Acinetobacter baumannii and Pseudomonas aeruginosa

Novel alginate hydrogels with silver nanoparticles (AgNPs) and honey components were produced with the aim to target multidrug-resistant bacterial strains causing nosocomial wound infections. AgNP synthesis was optimized in highly concentrated honey solutions so that a 5-month stable, colloid solution with 50% of honey and similar to 8 nm AgNPs at neutral pH was obtained. The colloid solution was further used to produce nano-composite Ag/alginate hydrogels in different forms (microbeads, microfibers and discs) that retained all AgNPs and high fractions of honey components (40-60%) as determined by the phenol-sulfuric acid and Folin-Ciocalteu methods. The hydrogels were characterized by UV-Vis spectroscopy and Fourier-transform infrared-attenuated total reflectance spectroscopy while the antibacterial activity was investigated against a broad spectrum of Gram-negative and Gram-positive bacteria, including 13 multi-resistant clinical strains of Acinetobacter baumannii, one clinical strain of Pseudomonas aeruginosa and one clinical strain of Staphylococcus aureus. At the total released silver concentration of similar to 9 mu g/ml, the hydrogels exhibited strong bactericidal activity against standard and most of the investigated multi-resistant hospital strains with the exemption of 3 clinical strains of A. baumannii in which antibacterial effects were absent. These results reveal the need for further in-depth studies of bacterial resistance mechanisms and, in the same time, potentials of the novel Ag/alginate hydrogels with honey components to combat wound infections and enhance healing as non-sticky, antibacterial, and bioactive dressings

Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models

Parkinson disease (PD) is a neurodegenerative disorder characterized by the abnormal intracellular accumulation of SNCA/α-synuclein. While the exact mechanisms underlying SNCA pathology are not fully understood, increasing evidence suggests the involvement of autophagy as well as lysosomal deficiencies. Because CTSD (cathepsin D) has been proposed to be the major lysosomal protease involved in SNCA degradation, its deficiency has been linked to the presence of insoluble SNCA conformers in the brain of mice and humans as well as to the transcellular transmission of SNCA aggregates. We here postulate that SNCA degradation can be enhanced by the application of the recombinant human proform of CTSD (rHsCTSD). Our results reveal that rHsCTSD is efficiently endocytosed by neuronal cells, correctly targeted to lysosomes and matured to an enzymatically active protease. In dopaminergic neurons derived from induced pluripotent stem cells (iPSC) of PD patients harboring the A53T mutation within the SNCA gene, we confirm the reduction of insoluble SNCA after treatment with rHsCTSD. Moreover, we demonstrate a decrease of pathological SNCA conformers in the brain and within primary neurons of a ctsd-deficient mouse model after dosing with rHsCTSD. Boosting lysosomal CTSD activity not only enhanced SNCA clearance in human and murine neurons as well as tissue, but also restored endo-lysosome and autophagy function. Our findings indicate that CTSD is critical for SNCA clearance and function. Thus, enzyme replacement strategies utilizing CTSD may also be of therapeutic interest for the treatment of PD and other synucleinopathies aiming to decrease the SNCA burden. Abbreviations: aa: amino acid; SNCA/α-synuclein: synuclein alpha; APP: amyloid beta precursor protein; BBB: blood brain barrier; BF: basal forebrain; CBB: Coomassie Brilliant Blue; CLN: neuronal ceroid lipofuscinosis; CNL10: neuronal ceroid lipofuscinosis type 10; Corr.: corrected; CTSD: cathepsin D; CTSB: cathepsin B; DA: dopaminergic; DA-iPSn: induced pluripotent stem cell-derived dopaminergic neurons; dox: doxycycline; ERT: enzyme replacement therapy; Fx: fornix, GBA/β-glucocerebrosidase: glucosylceramidase beta; h: hour; HC: hippocampus; HT: hypothalamus; i.c.: intracranially; IF: immunofluorescence; iPSC: induced pluripotent stem cell; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LSDs: lysosomal storage disorders; MAPT: microtubule associated protein tau; M6P: mannose-6-phosphate; M6PR: mannose-6-phosphate receptor; MB: midbrain; mCTSD: mature form of CTSD; neurofil.: neurofilament; PD: Parkinson disease; proCTSD: proform of CTSD; PRNP: prion protein; RFU: relative fluorescence units; rHsCTSD: recombinant human proCTSD; SAPC: Saposin C; SIM: structured illumination microscopy; T-insol: Triton-insoluble; T-sol: Triton-soluble; TEM: transmission electron microscopy, TH: tyrosine hydroxylase; Thal: thalamus