40 research outputs found

    Credit Scorecard for Corporate Clients based on Industries

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    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

    Nestin-Positive/SOX2−Negative Cells Mediate Adult Neurogenesis of Nigral Dopaminergic Neurons in Mice

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    The primary clinical motor symptoms of Parkinson’s disease (PD) result from loss of dopaminergic (DA) neurons in the substantia nigra (SN). Consequently, neurogenesis of this group of neurons in the adult brain has drawn considerable interest for the purpose of harnessing endogenous neurogenerative potential as well as devising better strategies for stem cell therapy for PD. However, the existence of adult neurogenesis for DA neurons within the SN remains controversial. To overcome technical and design limitations associated with previous studies, our group has developed a novel genetic mouse model for assessing adult nigral DA neurogenesis. This system utilizes transgenic mice that express a tamoxifen-activatable Cre recombinase (CreERT2) under the control of the neuronal progenitor cell promoters nestin or Sox2 leading to suppression of the DA neuron marker tyrosine hydroxylase (TH) via excision of exon 1 by flanking loxP sites in adult animals. This study reports that six months following initiation of a six week treatment with tamoxifen mice with nestin-mediated Th excision displayed a significant reduction in TH+ neurons in the SN. This finding indicates that nestin-expressing cells regenerate DA neurons within the SN of adult animals. Interestingly, no reduction was observed in TH+ cells following Sox2-mediated Th excision suggesting that a nestin+/SOX2‒ precursor cell population drives DA neurogenesis in the adult SN. This information represents a substantial leap in current knowledge of adult DA neurogenesis, will enable improved in vitro and in vivo modeling, as well as facilitate the harnessing of this process for therapeutic intervention for PD

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

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    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 autophagic 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, but also restored endo-lysosome and autophagy function in human and murine neurons as well as tissue. 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.authorsversionepub_ahead_of_prin

    Efeito de reguladores de crescimento sobre os teores de ácido ascórbico e carboidratos solúveis de morango (Fragaria hybridus)

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    Several growth regulators were sprayed on strawberry plants: SADH (5000 ppm), CCC (2000 ppm), IAA (10 ppm, 3 times), GA 10 ppm, 3 times) and GA (550 ppm), Ascorbic acid, dry weight and soluble carbohydrates contents of fruits were determined. Statistically differences were not observed between treatments and control. Dry weight varied from 7.62 to 9.53%. Ascorbic acid content varied from 35.88 to 71.81 mg/100 g on fresh weight basis. Mean values of soluble carbohydrates, in grams/100 g on fresh weight basis, were total (5.58), sucrose (1.01), glucose (1.63) and frutose (1.54).Foram feitas aplicações dos seguintes reguladores de crescimento em morango (Fragarm hybridus): SADH a 5000 ppm, CCC a 2000 ppm, ATA a 10 ppm (3 aplicações), ácido giberélico a 10 ppm (3 aplicações) e 550 ppm. Análises de peso seco, ácido ascórbico e carboidratos solúveis dos frutos foram efetuadas a fim de se estudar o efeito desses reguladores de crescimento. Não foram detectadas diferenças significativas entre os diversas tratamentos e o controle. O peso seco variou de 7,62 a 9,53%. O conteúdo de ácido ascórbico variou de 35,88 a 71,81 mg/100 g de peso fresco. Os teores médios de carboidratos solúveis, expresso em g/100 g peso fresco, foram: totais (5,58), sacarose (1,01), glucose (1,63) e frutose (1,54)

    Micro-nutrients in fertilisers

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    RESP-402

    Characterization of scaffolds based on chitosan and collagen with glycosaminoglycans and sodium alginate addition

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    Scaffolds based on chitosan (CTS), collagen (Coll), and glycosaminoglycans (GAGs) cross-linked by sodium alginate (SA) were obtained with the use of the freeze-drying method. They were characterized by different analyses, e.g. infrared spectroscopy, SEM images and differential scanning calorimetry. Furthermore, bio-mechanical properties of the scaffolds were determined in a biomimetic bioreactor. The results showed that the scaffolds based on chitosan, collagen, and glycosaminoglycans cross-linked by sodium alginate are stable in aqueous environment. The infrared spectroscopy analysis showed the hydrogen bond formation between polymers. Scaffolds presented open-pores structures even after a 3-day long analysis in a perfusion bioreactor. The obtained results indicate that the addition of sodium alginate slightly modified biomechanical properties
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