CD74 and CD44 Expression on CTCs in Cancer Patients with Brain Metastasis

Up to 40% of advance lung, melanoma and breast cancer patients suffer from brain metastases (BM) with increasing incidence. Here, we assessed whether circulating tumor cells (CTCs) in peripheral blood can serve as a disease surrogate, focusing on CD44 and CD74 expression as prognostic markers for BM. We show that a size-based microfluidic approach in combination with a semi-automated cell recognition system are well suited for CTC detection in BM patients and allow further characterization of tumor cells potentially derived from BM. CTCs were found in 50% (7/14) of breast cancer, 50% (9/18) of non-small cell lung cancer (NSCLC) and 36% (4/11) of melanoma patients. The next-generation sequencing (NGS) analysis of nine single CTCs from one breast cancer patient revealed three different CNV profile groups as well as a resistance causing ERS1 mutation. CD44 and CD74 were expressed on most CTCs and their expression was strongly correlated, whereas matched breast cancer BM tissues were much less frequently expressing CD44 and CD74 (negative in 46% and 54%, respectively). Thus, plasticity of CD44 and CD74 expression during trafficking of CTCs in the circulation might be the result of adaptation strategies.     

Age-Dependent Control of Collagen-Dependent Platelet Responses by Thrombospondin-1—Comparative Analysis of Platelets from Neonates,Children, Adolescents,and Adults

Platelet function is developmentally regulated. Healthy neonates do not spontaneously bleed, but their platelets are hypo-reactive to several agonists. The mechanisms underlying immature platelet function in neonates are incompletely understood. This critical issue remains challenging for the establishment of age-specific reference ranges. In this study, we evaluated platelet reactivity of five pediatric age categories, ranging from healthy full-term neonates up to adolescents (11–18 years) in comparison to healthy adults (>18 years) by flow cytometry. We confirmed that platelet hypo-reactivity detected by fibrinogen binding, P-selectin, and CD63 surface expression was most pronounced in neonates compared to other pediatric age groups. However, maturation of platelet responsiveness varied with age, agonist, and activation marker. In contrast to TRAP and ADP, collagen-induced platelet activation was nearly absent in neonates. Granule secretion markedly remained impaired at least up to 10 years of age compared to adults. We show for the first time that neonatal platelets are deficient in thrombospondin-1, and exogenous platelet-derived thrombospondin-1 allows platelet responsiveness to collagen. Platelets from all pediatric age groups normally responded to the C-terminal thrombospondin-1 peptide RFYVVMWK. Thus, thrombospondin-1 deficiency of neonatal platelets might contribute to the relatively impaired response to collagen, and platelet-derived thrombospondin-1 may control distinct collagen-induced platelet responses.     

Influence of dry grinding in a ball mill on the length of multiwalled carbon nanotubes and their dispersion and percolation behaviour in melt mixed polycarbonate composites

Ball milling of carbon nanotubes (CNTs) in the dry state is a common way to produce tailored CNT materials for composite applications, especially to adjust nanotube lengths. For Nanocyl^TM NC7000 nanotube material before and after milling for 5 and 10 h the length distributions were quantified using TEM analysis, showing decreases of the mean length to 54% and 35%, respectively. With increasing ball milling time in addition a decrease of agglomerate size and an increase of packing density took place resulting in a worse dispersability in aqueous surfactant solutions. In melt mixed CNT/polycarbonate composites produced using masterbatch dilution step, the electrical properties, the nanotube length distribution after processing, and the nano- and macrodispersion of the nanotubes were studied. The slight increase in the electrical percolation threshold in the melt mixed composites with ball milling time of CNTs can be assigned to lower nanotube lengths as well as the worse dispersability of the ball milled nanotubes. After melt compounding, the mean CNT lengths were shortened to 31%, 50%, and 66% of the initial lengths of NC7000, NC7000-5 h, and NC7000-10 h, respectively.     

Properties of set-style skim milk yoghurt as affected by an enzymatic or Maillard reaction induced milk protein oligomerisation

Protein oligomers (2.9 × 10⁴-3.0 × 10⁵ g/mol) were introduced into yoghurt in amounts of 15-37% of the total protein by an enzymatic modification of proteins in yoghurt milk by lactoperoxidase, laccase or glucose oxidase as well as by a dry matter increase of yoghurt milk with sodium caseinate/lactose, sodium caseinate/pectin and total milk protein/lactose Maillard products. Yoghurt from enzymatically treated milk was characterised by an up to 10% lower acidity, up to 47% diminished gel strength and up to 18% decreased whey drainage than yoghurt from untreated milk. Yoghurt from protein/saccharide Maillard product enriched milk exhibited up to 4% reduced acidity, up to 27% increased acetic aldehyde content as well as up to 58% decreased whey drainage in relation to yoghurt from untreated protein/saccharide mixture enriched milk. Sensorically, yoghurt from enzymatically treated milk as well as from protein/saccharide Maillard product enriched milk was described by an even and whey-draining appearance, by a soft, homogeneous and creamy consistency as well as by a mild, less yoghurt characteristic taste and smell.This study for the first time presents an overview over the impact of novel protein oligomerisation techniques on physicochemical and sensory properties of yoghurt in regard to possible practical applications of an enzymatic as well as Maillard reaction induced oligomerisation in complex food systems.     

Infants' joint attention skills predict toddlers' emerging mental state language.

To assess predictive relations between joint attention skills, intention understanding, and mental state vocabulary, 88 children were tested with measures of comprehension of gaze and referential pointing, as well as the production of declarative gestures and the comprehension and production of imperative gestures, at the ages of 7–18 months. Infants' intention-based imitation skills were assessed at 12, 15, and 18 months. At the ages of 24 and 36 months, toddlers' internal state lexicon was evaluated by parents with a German adaptation of the Mental State Language Questionnaire (Olineck & Poulin-Dubois, 2005). Regression analyses revealed that 9-months-olds' comprehension of referential pointing contributed significantly to the prediction of intention-based imitation skills at 15 months, as well as to children's volition and cognition vocabularies at 24 and 36 months, respectively. Moreover, 12-month-olds' comprehension of an imperative motive was shown to selectively predict toddlers' use of volition terms at 24 months. Overall, these results provide empirical evidence for both general and specific developmental relations between preverbal communication skills and mental state language, thus implying developmental continuity within the social domain in the first 3 years of life. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Randomized OBDDs for the most significant bit of multiplication need exponential space

Integer multiplication as one of the basic arithmetic functions has been in the focus of several complexity theoretical investigations and ordered binary decision diagrams (OBDDs) are one of the most common dynamic data structures for Boolean functions. Only in 2008 the question whether the deterministic OBDD complexity of the most significant bit of integer multiplication is exponential has been answered affirmatively. Since probabilistic methods have turned out to be useful in almost all areas of computer science, one may ask whether randomization can help to represent the most significant bit of integer multiplication in smaller size. Here, it is proved that the randomized OBDD complexity is also exponential.