Synthetic Antibody Mimics Based on Cancer-Targeting Immunostimulatory Peptides

De novo cancer-targeting immunostimulatory peptides have been designed and developed as synthetic antibody mimics. A series of bifunctional peptides incorporating NKp30-binding and NK-cell-activating domains were synthesized as linear dimers and then extended into branching trimeric peptides by the incorporation of GRP78-targeting and tumor-cell-binding sequences. A selected trimeric peptide from this small set of peptides displayed binding capabilities on GRP78⁺ HepG2 and A549 target cells. Cell binding diminished in the presence of an anti-GRP78 peptide blocker, thus suggesting GRP78-binding dependence. Similarly, the selected trimeric peptide was also found to exhibit NK cell binding in an NKp30-dependent manner, which translated into NK cell activation as indicated by cytokine secretion. In co-culture, fluorescence microscopy revealed that the target GFP-expressing A549 cells were visibly associated with the effector NK cells when pre-activated with lead trimeric peptide. Accordingly, A549 cells were found to be compromised, as evidenced by the loss of GFP signal and notable detection of early-/late-stage apoptosis. Investigation of the immunological markers related to toxicity revealed detectable secretion of pro-inflammatory cytokines and chemokines, including IFN-γ, TNF-α, and IL-8. Furthermore, administration of peptide-activated NK cells into A549-tumor-bearing mice resulted in a consistent decrease in tumor growth when compared to the untreated control group. Taken together, the identification of a lead trimeric peptide capable of targeting and activating NK cells’ immunotoxicity directly towards GRP78⁺/B7H6^- tumors provides a novel proof-of-concept for the development of cancer-targeting immunostimulatory peptide ligands that mimic antibody-targeting and -activating functions related to cancer immunotherapy applications.     

Developmental psychopathology in infancy: Illustration from the study of maltreated youngsters.

Infancy is a period of rapid developmental change, characterized by transitions and qualitative reorganizations within and among biological, social, emotional, cognitive, and linguistic systems. Consequently, it is argued that it is inappropriate to focus on discrete symptomatology to infer the presence of nascent or incipient infant psychopathology. Rather, disorders in infancy are best conceptualized as relational psychopathologies, that is, as consequences of dysfunction in the parent–child-environment system. Research in the area of child maltreatment is used to illustrate the developmental psychopathology perspective as it applies to relational disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Quantitative and Qualitative Evaluation of Chondroitin Sulfate in Dietary Supplements

We propose to evaluate the amount and quality of chondroitin sulfate (CS) from several food supplement preparations in the form of tablets, caplets, or capsules containing CS in varying contents and formulations in the presence of various additives and ingredients, with no other pretreatment than centrifugation to remove insoluble material. To quantify CS, two different analytical approaches were applied after their validation: specific and sensitive agarose-gel electrophoresis and strong-anion exchange–high-performance liquid chromatography (SAX-HPLC) determination of the constituent disaccharides after treatment with specific chondroitin lyases. The CS content in finished products evaluated using the two specific validated methods were found to conform to the label specifications. It is worth mentioning that the quantitative determinations have been performed using a very high pure European Pharmacopeia CS reference standard having substantially the same properties as the food supplement CS samples. Furthermore, by means of the specific agarose-gel elctrophoresis approach, we can exclude the presence in the nutraceuticals of other sulfated polysaccharides produced by extraction from tissues, in particular heparin, heparan sulfate, and dermatan sulfate. The SAX-HPLC separation of unsaturated disaccharides for the nutraceutical CS was also used to evaluate its quality and the possible origin. No disulfated disaccharides typical of CS from cartilaginous fishes, making the charge density lower than 1.0, were found, thus confirming the bovine or porcine origin, the most common sources of this “terrestrial” polysaccharide. Finally, high-performance size-exclusion chromatography (HPSEC) analysis was applied to evaluate the CS molecular mass in food supplements also in the presence of additives and other ingredients. This analytical approach confirmed that the nutraceutical CS samples are of high molecular mass and are not degraded during the food supplement preparations. In conclusion, this multianalytical approach can be used in the direct quantitation and evaluation of the quality and the possible origin of CS contained in food supplement formulations.     

Effects of maltreatment on school-age children's socioemotional development: Assessments in a day-camp setting.

This study assessed the impact of different forms of maltreatment on the socioemotional development of 5- to 11-year-old children in a day-camp setting. Obtained measures of self-esteem and peer relations for 70 neglected, emotionally abused and/or physically abused children, and 67 demographically matched nonmaltreated comparison children. Completed counselor assessments of the children's self-esteem and provided both counselor and peer ratings of the children's prosocial, aggressive, and withdrawn behavior. Found maltreated children to score lower than the comparison children on the self-esteem and prosocial measures and higher on the withdrawn behavior ratings. Found welfare dependency to exert an independent additive negative effect, beyond maltreatment history, on the socioemotional development of the children. Results are discussed in relation to past studies of high-risk children and existing theories of developmental psychopathology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Design and Qualification of Pr–Fe–Cu–B Alloys for the Additive Manufacturing of Permanent Magnets

The direct use of an advanced binder-free additive manufacturing technique, namely laser powder bed fusion (L-PBF), does not easily allow obtaining variously shaped, fully dense Nd–Fe–B magnets with high coercivity. The process inherently leads to the re-melting of the powder and appearance/disappearance of undesired/desired microstructural features responsible for low and large coercivity. In this work, the development of a useful microstructure responsible for high coercivity in Pr₂₁Fe_73.5Cu₂B_3.5 and Nd₂₁Fe_73.5Cu₂B_3.5 alloys and a possible way to produce fully dense permanent magnets via additive manufacturing processes is demonstrated using: (i) suction casting technique, which provides a high cooling rate and thus similar microstructures as in L-PBF but requires only very small amounts of powder; (ii) conventional L-PBF processing using kg of powder, and (iii) a subsequent annealing treatment that is similar to a conventional sintering treatment. The subsequent heat treatment is necessary to develop high coercivity by forming a novel microstructure: hard magnetic (Nd,Pr)₂Fe₁₄B grains embedded in a matrix of intermetallic (Nd,Pr)₆Fe₁₃Cu phase. Furthermore, it is demonstrated that Pr₂₁Fe_73.5Cu₂B_3.5 exhibits a higher coercivity than Nd₂₁Fe_73.5Cu₂B_3.5 because of a finer and more homogeneous grain size distribution of the Pr₂Fe₁₄B phase. The final L-PBF printed Pr₂₁Fe_73.5Cu₂B_3.5 samples provide a coercivity of 0.75 T.     

Exchange Coupling in MnAlC/α-Fe Nanocomposite Magnets

Nanostructured composite materials consisting of exchange-coupled hard and soft magnetic phases are proposed as alternative for the development of high-energy product permanent magnets. In this work, we have examined the effects of soft magnetic α-Fe addition on the structure and magnetic properties of powders composed of hard magnetic Mn_54.3Al₄₄C_1.7 compound. The optimum melt-spun ribbon precursor (with τ-phase structure, with magnetization of 88 emu/g and coercive field of 1.6 kOe) was obtained after annealing the ribbons at 500 ^°C for 20 min. After the combination between the soft and the optimized hard phase, the intensity of τ-phase peaks measured by X-ray diffraction decreases. These changes can also be seen in the magnetic properties. The coercivity (～ 500 Oe) tends to decrease with the annealing temperature, while the magnetization tends to increase up to 141 emu/g. Evidence of good exchange coupling between particles of Mn_54.3Al₄₄C_1.7 and α-Fe, in the produced composite, was proved by the hysteresis loop and its corresponding Thamm-Hesse analysis.     

Tannase from Aspergillus melleus improves the antioxidant activity of green tea: purification and biochemical characterisation

Tannase is an inducible enzyme used extensively in food, feed, pharmaceutical and chemical industries. In this study, tannase production and its biochemical properties were evaluated. From 42 Aspergillus strains analysed for potential tannase selection, Aspergillus melleus yielded the best results. Production was analysed using a complete factorial planning of 2³. Maximum activity (452.55 U mL^?1) was obtained in the optimal conditions of substrate (5.0 g), initial moisture (60%), tannic acid (2%) and 48 h of fermentation. The molecular weight of the purified enzyme was estimated as 69.52 kDa; its optimum temperature and pH were 40 °C and 5.5, respectively. Regarding the chemical effectors used, tannase was inhibited by ZnCl₂, ZnSO₄, Triton X‐100 and SDS. The addition of tannase to green tea improved its antioxidant potential by approximately 85% when compared to the control. The present results suggest that tannase may be used as an adjuvant to increase the antioxidant potential of green tea.     

Gis-based procedures for hydropower potential spotting

The increasing demand for energy, especially from renewable and sustainable sources, spurs the development of small hydropower plants and encourages investment in new survey studies. Preliminary hydropower survey studies usually carry huge uncertainties about the technical, economic and environmental feasibility of the undeveloped potential. This paper presents a methodology for large-scale survey of hydropower potential sites to be applied in the inception phase of hydroelectric development planning. The sequence of procedures to identify hydropower sites is based on remote sensing and regional streamflow data and was automated within a GIS-based computational program: Hydrospot. The program allows spotting more potential sites along the drainage network than it would be possible in a traditional survey study, providing different types of dam-powerhouse layouts and two types (operating modes) of projects: run-of-the-river and storage projects. Preliminary results from its applications in a hydropower-developed basin in Brazil have shown Hydrospot’s limitations and potentialities in giving support to the mid-to-long-term planning of the electricity sector.