The importance of ‘tooglies’ to the ethnography of F.E. Williams,government anthropologist

The theoretical orientation, encapsulated in the semi‐serious concept of ‘tooglies'of F.E. Williams, government anthropologist for the Territory of Papua in the inter‐war period, is considered. His ideas about culture change are contrasted with those of Bronislaw Malinowski, who acted as his mentor at one time. His treatment of the social organisational anomaly of Sogeri Koiari ‘sex affiliation’, often cited as a case of parallel bilineal descent, is compared with Margaret Mead's analysis of the ‘Mundugumor ropes’, which is classed as the opposite, cross‐sex bilineal descent. It is shown that Williams was able to get a clearer insight into this anomalous data than Mead and Fortune, and, on the whole, worked with an understanding of culture and Papuan social organisation that presages the relational approach of today.     

A reversal learning task detects cognitive deficits in a Dachshund model of late-infantile neuronal ceroid lipofuscinosis

The neuronal ceroid lipofuscinoses (NCLs) are autosomal recessive lysosomal storage diseases characterized by progressive neurodegeneration and by accumulation of autofluorescent storage material in the central nervous system and other tissues. One of the most prominent clinical signs of NCL is progressive decline in cognitive function. We previously described a frame shift mutation of TPP1 in miniature long-haired Dachshunds which causes an early-onset form of NCL analogous to classical late-infantile onset NCL (CLN2) in children. Dogs homozygous for the TPP1 mutation exhibit progressive neurological signs similar to those exhibited by human patients. In order to establish biomarkers for evaluating the efficacy of ongoing therapeutic studies in this canine model, we characterized phenotypic changes in 13 dogs through 9 months of age. Cognitive function was assessed using a T-maze reversal learning (RL) task. Cognitive dysfunction was detected in affected dogs as early as 6 months of age and worsened as the disease progressed. Physical and neurological examination, funduscopy and electroretinography (ERG) were performed at regular intervals. Only the changes in ERG responses showed signs of disease progression earlier than the RL task. In the later stages of the disease clinical signs of visual and motor deficits became evident. The visual and motor deficits were not severe enough to affect the performance of dogs in the T-maze. Declining performance on the RL task is a sensitive measure of higher-order cognitive dysfunction which can serve as a useful biomarker of disease progression.     

A stochastic flowering model describing an asynchronically flowering set of trees

A general stochastic model is presented that simulates the time course of flowering of individual trees and populations, integrating the synchronization of flowering both between and within trees. Making some hypotheses, a simplified expression of the model, called the 'shoot' model, is proposed, in which the synchronization of flowering both between and within trees is characterized by specific parameters. Two derived models, the 'tree' model and the 'population' model, are presented. They neglect the asynchrony of flowering, respectively, within trees, and between and within trees. Models were fitted and tested using data on flowering of Psidium cattleianum observed at study sites at elevations of 200, 520 and 890 m in Reunion Island. The 'shoot' model fitted the data best and reproduced the strong irregularities in flowering shown by empirical data. The asynchrony of flowering in P. cattleianum was more pronounced within than between trees. Simulations showed that various flowering patterns can be reproduced by the 'shoot' model. The use of different levels of organization of the general model is discussed.     

Survival analysis in clinical trials: past developments and future directions

The field of survival analysis emerged in the 20th century and experienced tremendous growth during the latter half of the century. The developments in this field that have had the most profound impact on clinical trials are the Kaplan-Meier (1958, Journal of the American Statistical Association 53, 457-481) method for estimating the survival function, the log-rank statistic (Mantel, 1966, Cancer Chemotherapy Report 50, 163-170) for comparing two survival distributions, and the Cox (1972, Journal of the Royal Statistical Society, Series B 34, 187-220) proportional hazards model for quantifying the effects of covariates on the survival time. The counting-process martingale theory pioneered by Aalen (1975, Statistical inference for a family of counting processes, Ph.D. dissertation, University of California, Berkeley) provides a unified framework for studying the small- and large-sample properties of survival analysis statistics. Significant progress has been achieved and further developments are expected in many other areas, including the accelerated failure time model, multivariate failure time data, interval-censored data, dependent censoring, dynamic treatment regimes and causal inference, joint modeling of failure time and longitudinal data, and Baysian methods.     

Binding model for eriodictyol to Jun-N terminal kinase and its anti-inflammatory signaling pathway

The anti-inflammatory activity of eriodictyol and its mode of action were investigated. Eriodictyol suppressed tumor necrosis factor (mTNF)-α, inducible nitric oxide synthase (miNOS), interleukin (mIL)-6, macrophage inflammatory protein (mMIP)-1, and mMIP-2 cytokine release in LPS-stimulated macrophages. We found that the anti-inflammatory cascade of eriodictyol is mediated through the Toll-like Receptor (TLR)4/CD14, p38 mitogen-activated protein kinases (MAPK), extracellular-signalregulated kinase (ERK), Jun-N terminal kinase (JNK), and cyclooxygenase (COX)-2 pathway. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that eriodictyol exhibits good binding affinity to JNK, 8.79 × 10⁵ M^-1. Based on a docking study, we propose a model of eriodictyol and JNK binding, in which eriodictyol forms 3 hydrogen bonds with the side chains of Lys55, Met111, and Asp169 in JNK, and in which the hydroxyl groups of the B ring play key roles in binding interactions with JNK. Therefore, eriodictyol may be a potent anti-inflammatory inhibitor of JNK. [BMB Reports 2013; 46(12): 594-599]     

Direct Mouse Trauma/Burn Model of Heterotopic Ossification

Heterotopic ossification (HO) is the formation of bone outside of the skeleton which forms following major trauma, burn injuries, and orthopaedic surgical procedures. The majority of animal models used to study HO rely on the application of exogenous substances, such as bone morphogenetic protein (BMP), exogenous cell constructs, or genetic mutations in BMP signaling. While these models are useful they do not accurately reproduce the inflammatory states that cause the majority of cases of HO. Here we describe a burn/tenotomy model in mice that reliably produces focused HO. This protocol involves creating a 30% total body surface area partial thickness contact burn on the dorsal skin as well as division of the Achilles tendon at its midpoint. Relying solely on traumatic injury to induce HO at a predictable location allows for time-course study of endochondral heterotopic bone formation from intrinsic physiologic processes and environment only. This method could prove instrumental in understanding the inflammatory and osteogenic pathways involved in trauma-induced HO. Furthermore, because HO develops in a predictable location and time-course in this model, it allows for research to improve early imaging strategies and treatment modalities to prevent HO formation.     

Characterization of bimodal cell death of insect cells in a rotating‐wall vessel and shaker flask

In previous publications, we reported the benefits of a high‐aspect rotating‐wall vessel (HARV) over conventional bioreactors for insect‐cell cultivation in terms of reduced medium requirements and enhanced longevity. To more fully understand the effects that HARV cultivation has on longevity, the present study characterizes the mode and kinetics of Spodoptera frugiperda cell death in this quiescent environment relative to a shaker‐flask control. Data from flow cytometry and fluorescence microscopy show a greater accumulation of apoptotic cells in the HARV culture, by a factor of at least 2 at the end of the cultivation period. We present a kinetic model of growth and bimodal cell death. The model is unique for including both apoptosis and necrosis, and further, transition steps within the two pathways. Kinetic constants reveal that total cell death is reduced in the HARV and the accumulation of apoptotic cells in this vessel results from reduced depletion by lysis and secondary necrosis. The ratio of early apoptotic to necrotic cell formation is found independent of cultivation conditions. In the model, apoptosis is only well represented by an integral term, which may indicate its dependence on accumulation of some factor over time; in contrast, necrosis is adequately represented with a first‐order term. Cell‐cycle analysis shows the percent of tetraploid cells gradually decreases during cultivation in both vessels. For example, between 90% and 70% viability, tetraploid cells in the HARV drop from 43 ± 1% to 24 ± 4%. The data suggests the tetraploid phase as the likely origin for apoptosis in our cultures. Possible mechanisms for these changes in bimodal cell death are discussed, including hydrodynamic forces, cell–cell interactions, waste accumulation, and mass transport. These studies may benefit insect‐cell cultivation by increasing our understanding of cell death in culture and providing a means for further enhancing culture longevity. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 64: 14–26, 1999.     

Estimating regression parameters and degree of dependence for multivariate failure time data

Multivariate failure time data are frequently encountered in longitudinal studies when subjects may experience several events or when there is a grouping of individuals into a cluster. To take into account the dependence of the failure times within the unit (the individual or the cluster) as well as censoring, two multivariate generalizations of the Cox proportional hazards model are commonly used. The marginal hazard model is used when the purpose is to estimate mean regression parameters, while the frailty model is retained when the purpose is to assess the degree of dependence within the unit. We propose a new approach based on the combination of the two aforementioned models to estimate both these quantities. This two-step estimation procedure is quicker and more simple to implement than the EM algorithm used in frailty models estimation. Simulation results are provided to illustrate robustness, consistency, and large-sample properties of estimators. Finally, this method is exemplified on a diabetic retinopathy study in order to assess the effect of photocoagulation in delaying the onset of blindness as well as the dependence between the two eyes blindness times of a patient.