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Modulation of the CD40-CD40 ligand interaction using human anti-CD40 single-chain antibody fragments obtained from the n-CoDeR phage display library

CD40 plays a central regulatory role in the immune system and antibodies able to modulate CD40 signalling may consequently have a potential in immunotherapy, in particular for treatment of lymphomas and autoimmune disease like multiple sclerosis. As a first step to achieve this goal, we describe the selection and characterization of a novel set of fully human anti-CD40 antibody fragments (scFv) fr

Length of the antibody heavy chain complementarity determining region 3 as a specificity-determining factor

lThe antigen binding site of an antibody is made up of residues residing in six hypervariable loops of the heavy and light chains. In most cases several or all of these loops are required for the establishment of the antigen-binding surface. Five of these loops display a limited diversity in length and sequence while the third complementarity determining region (CDR) of the heavy chain is highly d

A new cell line-based neutralization assay for primary HIV type 1 isolates

Simple and standardized assays for detection and quantification of neutralizing antibodies to primary HIV-1 isolates are needed in research on HIV-1 vaccines and pathogenesis. Here we describe a new HIV-1 neutralization assay that is based on plaque formation in U87.CD4-CCR5 and U87.CD4-CXCR4 cells, which is an attractive alternative to peripheral blood mononuclear cell-based assays. Infected cell

Mutation in cystatin C gene causes hereditary brain haemorrhage

Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disorder in which a cysteine proteinase inhibitor, cystatin C, is deposited as amyloid fibrils in the cerebral arteries of patients and leads to massive brain haemorrhage and death in young adults. A full length cystatin C cDNA probe revealed a mutation in the codon for leucine at position 68 which abolishes an Alu I restric

The Cognitive Interview and its effect on witnesses' confidence

Today there is ample evidence that the Cognitive Interview (CI) enhances witnesses' memory. However, less is known about how the CI affects eyewitnesses' confidence. To address this shortcoming we conducted a study analyzing how realism in confidence was affected by the CI. All participants (n = 79) were first shown a filmed kidnapping. After 2 weeks we interviewed one-third of the participants ac

Parental care and adaptive brood sex ratio manipulation in birds.

Under many circumstances, it might be adaptive for parents to bias the investment in offspring in relation to sex. Recently developed molecular techniques that allow sex determination of newly hatched offspring have caused a surge in studies of avian sex allocation. Whether females bias the primary brood sex ratio in relation to factors such as environmental and parental quality is debated. Progre

Protein D, the glycerophosphodiester phosphodiesterase from Haemophilus influenzae with affinity for human immunoglobulin D, influences virulence in a rat otitis model

A mutant lacking the ability to express the surface-exposed lipoprotein protein D was constructed by linker insertion and deletion mutagenesis of a cloned DNA insert containing the protein D structural gene from a nontypeable Haemophilus influenzae strain (NTHi). An isogenic NTHi mutant was isolated after transformation of genetically competent bacteria. The transformant was unreactive to a protei

A new type of long gamma-ray burst

We consider gamma-ray bursts (GRBs) produced by the merger of a massive white dwarf with a neutron star. We show that these are likely to produce long-duration GRBs, in some cases definitely without an accompanying supernova, as observed recently. This class of burst would have a strong correlation with star formation, and occur close to the host galaxy. However, rare members of the class need not

Synthesis of a C-glycoside analogue of beta-D-galactosyl hydroxynorvaline and its use in immunological studies

A C-linked isostere of beta-D-galactosylated hydroxynorvaline has been prepared in eight steps from per-O-benzylated galactopyranolactone. Addition of a homoallylic Grignard reagent to the lactone, reduction of the resulting hemiacetal with triethylsilane, and a Wittig reaction with Garner's aldehyde were key steps in this synthesis. The C-linked building block was then incorporated at position 26

Long-term effects of mammography screening: updated overview of the Swedish randomised trials

Background There has been much debate about the value of screening mammography. Here we update the overview of the Swedish randomised controlled trials on mammography screening up to and including 1996. The Kopparberg part of the Two-County trial was not available for the overview, but the continuation of the Malmo trial (MMST II) has been added. The article also contains basic data from the trial

White dwarfs and Galactic dark matter

We discuss the recent discovery by Oppenheimer et al. of old, cool white dwarf stars, which may be the first direct detection of Galactic halo dark matter. We argue here that the contribution of more mundane white dwarfs of the stellar halo and thick disc would contribute sufficiently to explain the new high velocity white dwarfs without invoking putative white dwarfs of the dark halo. This by no

The medium is the message: The media history of the press

This paper argues for the relevance of the media history of the press. Using a broad and open media concept, this perspective should be understood as the study of the construction and communication of the self-images and ideology of the press. Rather than describing the complex of problems as images that are ‘spread’ through one channel (newspapers) by one actor (the press), it should be seen as a

Minimal exclusion of plasma membrane proteins during retroviral envelope formation

The retrovirus forms its envelope by budding at the plasma membrane (PM). This process is primarily driven by its cytoplasmic core-precursor protein, Gag, as shown by the efficient formation of virus-like Gag particles in the absence of its envelope protein, Env. Most interestingly, several studies have demonstrated incorporation of various PM proteins into retrovirus, but the underlying mechanism

Four ways to understand what’s going on with the US, Denmark and Greenland

Feel overwhelmed but realise the need to understand what's going on? Academic analytical frameworks can help.European countries, and Denmark in particular, are scrambling to respond to threats from US officials over the future of Greenland.Having successfully taken out the leadership of Venezuela in a raid on January 3, an emboldened US government is talking about simply taking Greenland for itsel

Tracing Themes of Transhumanism and the Posthuman in Twenty-First Century Rewritings of Mary Shelley’s Frankenstein

Mary Shelley’s Frankenstein (1818) is one of the most famous works of fiction ever written and thus much has already been said about it. Recent criticism of the novel has identified the presence of transhumanist themes in Victor Frankenstein’s quest to create a new superior species and defeat death. Several thought-provoking retellings of Shelley’s story have been published since the formation of