Impaired natural killer cell function in hemophiliacs with or without continuous substitution

In the present study, 28 hemophiliacs substituted continuously and 5 hemophiliacs who had received almost no blood products were investigated. Cells of OKT 3+, OKT 4+, and OKT 8+ subsets were counted. Percoll separated fractions of peripheral blood mononuclear cells were examined by morphological criteria and were tested for NK cell activity. We found that the NK cell activity of both groups of hemophiliacs was decreased on testing Ficoll separated cells or low density Percoll separated cells. Normal NK cell activity was found in medium density cells of hemophiliacs. Two possible explanations are discussed: first, the NK cell activity may be suppressed in hemophiliacs and secondly, there may be a block in maturation of NK cell activity. It is unlikely that chronic substitution by blood products counts for these alterations. The possible role of chronic infections is discussed.     

Extended somatostatin treatment of a patient with bleeding ulcer.

The results of a 67 hour cyclic somatostatin continuous infusion in a patient with a bleeding ulcer are reported. The subject was a 65 year old male with very heavy gastrointestinal bleeding on the 9th postoperative day following a high BI-resection. Endoscopy revealed the bleeding to be caused by two residual ulcers in the area of the anastomosis. Somatostatin treatment led to an immediate cessation of the bleeding after 1 hour. Gastric secretion as well as gastrin, insulin and growth hormone levels were significantly inhibited by somatostatin. Endoscopy at the end of the treatment period showed two ulcers in the process of healing. The raised blood glucose levels caused by somatostatin were easily controlled with max. 14 IU cristalline insulin daily. Except for dryness in the mouth, no adverse side effects were apparent. There was no evidence from laboratory investigations of hemostatic defects or bleeding tendency in the patient.     

Current perspectives on biosimilars

In this work, an overview of the biosimilars market, pipeline and industry targets is discussed. Biosimilars typically have a shorter timeline for approval (8 years) compared to 12 years for innovator drugs and the development cost can be 10–20% of the innovator drug. The biosimilar pipeline is reviewed as well as the quality management system (QMS) that is needed to generate traceable, trackable data sets. One difference between developing a biosimilar compared to an originator is that a broader analytical foundation is required for biosimilars and advances made in developing analytical similarity to characterize these products are discussed. An example is presented on the decisions and considerations explored in the development of a biosimilar and includes identification of the best process parameters and methods based on cost, time, and titer. Finally factors to consider in the manufacture of a biosimilar and approaches used to achieve the target-directed development of a biosimilar are discussed.

     

Determination of glycan structure from tandem mass spectra

Glycans are molecules made from simple sugars that form complex tree structures. Glycans constitute one of the most important protein modifications and identification of glycans remains a pressing problem in biology. Unfortunately, the structure of glycans is hard to predict from the genome sequence of an organism. In this paper, we consider the problem of deriving the topology of a glycan solely from tandem mass spectrometry (MS) data. We study, how to generate glycan tree candidates that sufficiently match the sample mass spectrum, avoiding the combinatorial explosion of glycan structures. Unfortunately, the resulting problem is known to be computationally hard. We present an efficient exact algorithm for this problem based on fixed-parameter algorithmics that can process a spectrum in a matter of seconds. We also report some preliminary results of our method on experimental data, combining it with a preliminary candidate evaluation scheme. We show that our approach is fast in applications, and that we can reach very well de novo identification results. Finally, we show how to count the number of glycan topologies for a fixed size or a fixed mass. We generalize this result to count the number of (labeled) trees with bounded out degree, improving on results obtained using Pólya's enumeration theorem.     

Seasonality and resource availability control bacterial and archaeal communities in soils of a temperate beech forest

It was hypothesized that seasonality and resource availability altered through tree girdling were major determinants of the phylogenetic composition of the archaeal and bacterial community in a temperate beech forest soil. During a 2-year field experiment, involving girdling of beech trees to intercept the transfer of easily available carbon (C) from the canopy to roots, members of the dominant phylogenetic microbial phyla residing in top soils under girdled versus untreated control trees were monitored at bimonthly intervals through 16S rRNA gene-based terminal restriction fragment length polymorphism profiling and quantitative PCR analysis. Effects on nitrifying and denitrifying groups were assessed by measuring the abundances of nirS and nosZ genes as well as bacterial and archaeal amoA genes. Seasonal dynamics displayed by key phylogenetic and nitrogen (N) cycling functional groups were found to be tightly coupled with seasonal alterations in labile C and N pools as well as with variation in soil temperature and soil moisture. In particular, archaea and acidobacteria were highly responsive to soil nutritional and soil climatic changes associated with seasonality, indicating their high metabolic versatility and capability to adapt to environmental changes. For these phyla, significant interrelations with soil chemical and microbial process data were found suggesting their potential, but poorly described contribution to nitrification or denitrification in temperate forest soils. In conclusion, our extensive approach allowed us to get novel insights into effects of seasonality and resource availability on the microbial community, in particular on hitherto poorly studied bacterial phyla and functional groups.     

Visual shape recognition with contour propagation

A neural architecture is presented that encodes the visual space inside and outside of a shape. The contours of a shape are propagated across an excitable neuronal map and fed through a set of orientation columns, thus creating a pattern which can be viewed as a vector field. This vector field is then burned as synaptic, directional connections into a propagation map, which will serve as a “shape map”. The shape map identifies its own, preferred input when it is translated, deformed, scaled and fragmented, and discriminates other shapes very distinctively. Encoding visual space is much more efficient for shape recognition than determining contour geometry only.     

Structured model for denitrifier diauxic growth

We present a model for diauxic growth of denitrifying bacteria in which nitrate reductase synthesis kinetics dominate the overall growth kinetics. The model is based on the assumption of the existence of a nitrate respiration operon, thereby linking the rate of nitrate uptake to the activity of nitrate reductase. We show that this approach can model diauxic growth of Pseudomonas denitrificans by conducting experiments in which nitrate reductase activity was measured during both lag and ensuing exponential growth phases. We consistently observed the pattern of low nitrate reductase enzyme activity during the lag phase, increasing before the onset of growth. By fitting model parameters we were able to successfully match experimental data for growth, nitrate uptake, and enzyme activity level.     

Characterization of two methanopterin biosynthesis mutants of Methylobacterium extorquens AM1 by use of a tetrahydromethanopterin bioassay

An enzymatic assay was developed to measure tetrahydromethanopterin (H(4)MPT) levels in wild-type and mutant cells of Methylobacterium extorquens AM1. H(4)MPT was detectable in wild-type cells but not in strains with a mutation of either the orf4 or the dmrA gene, suggesting a role for these two genes in H(4)MPT biosynthesis. The protein encoded by orf4 catalyzed the reaction of ribofuranosylaminobenzene 5'-phosphate synthase, the first committed step of H(4)MPT biosynthesis. These results provide the first biochemical evidence for H(4)MPT biosynthesis genes in bacteria.