On some Sufficient Conditions for High Breakdown Point of ML Estimators

High breakdown point estimators LME(k) and LT E(k) for location and scale are obtained for symmetrical exponentially decreasing density family.This paper is partly financed by I-625/96 of Bulgarian Ministry of Education Science and Technologie

Modeling Influenza Antigenic Shift and Drift with LEGO Bricks

The significance of influenza virus for human health requires no introduction. Correspondingly, content related to the Influenza virus and its biology can be found in almost every microbiology and virology syllabus. Pedagogically, the influenza virus is an excellent choice for discussions of many key topics in microbiology/virology and their integration with issues in public health. The concepts of antigenic shift and drift are a classic example of influenza-related content in the classroom. They are central to understanding viral diversity and evolution and have direct application to vaccine design. Students often struggle to fully understand how both phenomena work mechanistically and thus have limited opportunity to gain an appreciation of the scientific principles behind the flu vaccine’s development and effectiveness. I have developed a simple exercise using conventional LEGO bricks to physically model antigenic shift and drift in order to aid student understanding. The exercise can be executed in any type and level of classroom for about 10 minutes and, if desired, extended to emphasize quantitative skills and molecular biology concepts or to trigger discussion of key issues in vaccine design. The manipulatives used are economical and easy to store, and pose no hazards in the classroom. No safety issues are associated with the described exercise

Dynamic Model Visualizing the Process of Viral Plaque Formation

In Microbiology and Virology courses, viral plaques are often presented to students as the way one can visualize viruses/bacteriophages. While students generally grasp the idea that counting plaques is essentially the same as counting viruses in their sample (assuming that one virus entering the cell is sufficient for productive infection), the process of plaque formation itself remains largely obscure. Many students fail to appreciate that viral plaques are actually a “laboratory-made” phenomenon allowing us to observe and study the growth of lytic viruses. The latter often presents a challenge for the interpretation of experimental data related to viral growth and drug discovery using plaque reduction assay. The hands-on model described here creates an opportunity for students to experience the process of viral plaque formation while engaging multiple senses and creating a lasting impression

eIF1A/eIF5B Interaction Network and its Functions in Translation Initiation Complex Assembly and Remodeling

Eukaryotic translation initiation is a highly regulated process involving multiple steps, from 43S pre-initiation complex (PIC) assembly, to ribosomal subunit joining. Subunit joining is controlled by the G-protein eukaryotic translation initiation factor 5B (eIF5B). Another protein, eIF1A, is involved in virtually all steps, including subunit joining. The intrinsically disordered eIF1A C-terminal tail (eIF1A-CTT) binds to eIF5B Domain-4 (eIF5B-D4). The ribosomal complex undergoes conformational rearrangements at every step of translation initiation; however, the underlying molecular mechanisms are poorly understood. Here we report three novel interactions involving eIF5B and eIF1A: (i) a second binding interface between eIF5B and eIF1A; (ii) a dynamic intramolecular interaction in eIF1A between the folded domain and eIF1A-CTT; and (iii) an intramolecular interaction between eIF5B-D3 and -D4. The intramolecular interactions within eIF1A and eIF5B interfere with one or both eIF5B/eIF1A contact interfaces, but are disrupted on the ribosome at different stages of translation initiation. Therefore, our results indicate that the interactions between eIF1A and eIF5B are being continuously rearranged during translation initiation. We present a model how the dynamic eIF1A/eIF5B interaction network can promote remodeling of the translation initiation complexes, and the roles in the process played by intrinsically disordered protein segments

Topology and Regulation of the Human eIF4A/4G/4H Helicase Complex in Translation Initiation

SummaryThe RNA helicase eIF4A plays a key role in unwinding of mRNA and scanning during translation initiation. Free eIF4A is a poor helicase and requires the accessory proteins eIF4G and eIF4H. However, the structure of the helicase complex and the mechanisms of stimulation of eIF4A activity have remained elusive. Here we report the topology of the eIF4A/4G/4H helicase complex, which is built from multiple experimentally observed domain-domain contacts. Remarkably, some of the interactions are continuously rearranged during the ATP binding/hydrolysis cycle of the helicase. We show that the accessory proteins modulate the affinity of eIF4A for ATP by interacting simultaneously with both helicase domains and promoting either the closed, ATP-bound conformation or the open, nucleotide-free conformation. The topology of the complex and the spatial arrangement of the RNA-binding surfaces offer insights into their roles in stimulation of helicase activity and the mechanisms of mRNA unwinding and scanning

An Infant Formula with Large, Milk Phospholipid-Coated Lipid Droplets Supports Adequate Growth and Is Well-Tolerated in Healthy, Term Asian Infants:A Randomized, Controlled Double-Blind Clinical Trial

Lipids are essential for healthy infant growth and development. The structural complexity of lipids in human milk is not present in infant milk formula (IF). A concept IF was developed mimicking more closely the structure and composition of human milk fat globules. The current study evaluates whether a concept IF with large, milk phospholipid-coated lipid droplets (mode diameter 3 to 5 μm) is equivalent to standard IF with regard to growth adequacy and safety in healthy, term Asian infants. In this randomized, double-blind, controlled trial, infants were randomized after parents decided to introduce formula. Infants received a standard IF with (Control) or without the specific prebiotic mixture scGOS/lcFOS (9:1 ratio; Control w/o prebiotics), or a Concept IF with large, milk phospholipid-coated lipid droplets and the prebiotic mixture. A group of 67 breastfed infants served as a reference. As a priori defined, only those infants who were fully intervention formula-fed ≤28 days of age were included in the equivalence analysis (Control n = 29; Control w/o prebiotics n = 28; Concept n = 35, per-protocol population). Primary outcome was daily weight gain during the first four months of life, with the difference between the Concept and Control as the key comparison of interest. Additionally, adverse events, growth and tolerance parameters were evaluated. Equivalence of daily weight gain was demonstrated between the Concept and Control group after additional correction for ethnicity and birthweight (difference in estimated means of 0.1 g/d, 90%CI [−2.30, 2.47]; equivalence margin +/− 3 g/d). No clinically relevant group differences were observed in secondary growth outcomes, tolerance outcomes or number, severity or relatedness of adverse events. This study corroborates that an infant formula with large, milk phospholipid-coated lipid droplets supports adequate growth and is well tolerated and safe for use in healthy infants

Infant formula containing large, milk phospholipid-coated lipid droplets and dairy lipids affects cognitive performance at school age

BackgroundBreastfeeding has been positively associated with infant and child neurocognitive development and function. Contributing to this effect may be differences between human milk and infant formula in the milk lipid composition and milk fat globule structure.ObjectiveTo evaluate the effects of an infant formula mimicking human milk lipid composition and milk fat globule structure on childhood cognitive performance.MethodsIn a randomized, controlled trial, healthy term infants received until 4 months of age either a Standard infant formula (n = 108) or a Concept infant formula (n = 115) with large, milk phospholipid coated lipid droplets and containing dairy lipids. A breastfed reference group (n = 88) was included. Erythrocyte fatty acid composition was determined at 3 months of age. Neurocognitive function was assessed as exploratory follow-up outcome at 3, 4, and 5 years of age using the Flanker test, Dimensional Change Card Sort (DCCS) test and Picture Sequence Memory test from the National Institutes of Health Toolbox Cognition Battery. Mann–Whitney U test and Fisher exact test were used to compare groups.ResultsErythrocyte omega-6 to -3 long-chain polyunsaturated fatty acid ratio appeared to be lower in the Concept compared to the Standard group (P = 0.025). At age 5, only the Concept group was comparable to the Breastfed group in the highest reached levels on the Flanker test, and the DCCS computed score was higher in the Concept compared to the Standard group (P = 0.021).ConclusionThese outcomes suggest that exposure to an infant formula mimicking human milk lipid composition and milk fat globule structure positively affects child neurocognitive development. Underlying mechanisms may include a different omega-3 fatty acid status during the first months of life.Clinical trial registrationhttps://onderzoekmetmensen.nl/en/trial/28614, identifier NTR3683 and NTR5538