Generation of “LYmph Node Derived Antibody Libraries” (LYNDAL) for selecting fully human antibody fragments with therapeutic potential

The development of efficient strategies for generating fully human monoclonal antibodies with unique functional properties that are exploitable for tailored therapeutic interventions remains a major challenge in the antibody technology field. Here, we present a methodology for recovering such antibodies from antigen-encountered human B cell repertoires. As the source for variable antibody genes, we cloned immunoglobulin G (IgG)-derived B cell repertoires from lymph nodes of 20 individuals undergoing surgery for head and neck cancer. Sequence analysis of unselected “LYmph Node Derived Antibody Libraries” (LYNDAL) revealed a naturally occurring distribution pattern of rearranged antibody sequences, representing all known variable gene families and most functional germline sequences. To demonstrate the feasibility for selecting antibodies with therapeutic potential from these repertoires, seven LYNDAL from donors with high serum titers against herpes simplex virus (HSV) were panned on recombinant glycoprotein B of HSV-1. Screening for specific binders delivered 34 single-chain variable fragments (scFvs) with unique sequences. Sequence analysis revealed extensive somatic hypermutation of enriched clones as a result of affinity maturation. Binding of scFvs to common glycoprotein B variants from HSV-1 and HSV-2 strains was highly specific, and the majority of analyzed antibody fragments bound to the target antigen with nanomolar affinity. From eight scFvs with HSV-neutralizing capacity in vitro, the most potent antibody neutralized 50% HSV-2 at 4.5 nM as a dimeric (scFv)₂. We anticipate our approach to be useful for recovering fully human antibodies with therapeutic potential.     

Statistical analysis of nitrate concentrations from the River Frome (Dorset) for the period 1965–76

SUMMARY. Statistical analysis has been carried out on 11 years (1965–75) weekly data of nitrate concentrations and discharge values from the R. Frome (Dorset). The results have shown a trend over the 11-year period with nitrate concentrations increasing by 0.11 mg NO_3-N 1⁻¹ per year. A predictive model for nitrate concentrations for 1976 was made and even though discharge conditions were extreme, the mean predicted nitrate concentration of 3.37 ± 0.136 mgNO_3-N1⁻¹ was very close to the observed mean nitrate concentration of 3.44mgN0_3-N1⁻¹.     

Culturally Situated Design Tools: Ethnocomputing from Field Site to Classroom

Ethnomathematics is the study of mathematical ideas and practices situated in their cultural context. Culturally Situated Design Tools (CSDTs) are web-based software applications that allow students to create simulations of cultural arts—Native American beadwork, African American cornrow hairstyles, urban graffiti, and so forth—using these underlying mathematical principles. This article is a review of the anthropological issues raised in the CSDT project: negotiating the representations of cultural knowledge during the design process with community members, negotiating pedagogical features with math teachers and their students, and reflecting on the software development itself as a cultural construction. The move from ethnomathematics to ethnocomputing results in an expressive computational medium that affords new opportunities to explore the relationships between youth identity and culture, the cultural construction of mathematics and computing, and the formation of cultural and technological hybridity.     

Oxygen consumption of active and inactive adult tiger beetles

ABSTRACT. Oxygen consumption (O₂) in six species of adult tiger beetles Cicindela spp. (Coleoptera: Cicindelidae) was correlated with body mass and temperature during rest. In beetles forced to run and/or right themselves continuously for 5–10 min at 25°C, O₂ was approximately 7–12 times as high as in resting individuals; the difference increased with increasing mass. Resting and active VO₂ were similar to previous results for other beetles, although the slope of log O₂ on log mass was lower. Detailed analysis suggests the existence of taxonomic and ecological correlates of resting metabolism. The possible ecological implications and adaptive advantages of these results for adult tiger beetles are discussed.     

Variation in chemical composition of the River Frome, England, from 1965 to 1972

This study covers a 7-year period from 1965 to 1972, and shows the variation in flow, water chemistry and throughput of nutrients. The annual discharge of the River Frome varied considerably from year to year, ranging from a mean value of 4.48 m³ sec⁻¹ in 1971 to one of 8.38 m³ sec⁻¹ in 1966. The mean annual nutrient losses calculated over all 7 years of study from the River Frome catchment were: Nitrate 11.4 kg ha⁻¹, phosphorus 0.49 kg ha⁻¹ and potassium 8.4 kg ha⁻¹. There has been an increase in annual throughput (in years of similar flow) of 21% in phosphate and 41% in nitrate from 1965 to 1972.