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FimH – Expression of recombinant proteins on the cell surface of bacteria

The expression and production of recombinant proteins in bacteria, such as E. coli is a long standing and well known procedure. However, expression in bacterial systems is limited due to cytoplasmic accumulation of the protein of interest (POI). Even though, various attempts have been made to prevent the accumulation of the desired protein in inclusion bodies, there is still no satisfactory solution available to overcome this problem. The present invention enables the expression of POI on the cell surface of bacteria, thereby preventing the cytoplasmic and periplasmic accumulation.

Innovatives Verfahren zur industriellen Herstellung von Aptameren

Aptamers are short, single-stranded DNA molecules that can specifically bind proteins due to their three-dimensional structure.
Because of their ability to deactivate different protein functions inside the cell, aptamers are already used successfully in the field of medical diagnosis, as therapeutic agents and in environmental analytics.
So far the technical production of single stranded DNA (ssDNA) within the range of more than 60 n has been linked to a grand
percentage of abbreviated respectively functionless by-products. Bigger aptamers with even 100 n or more have only been
practicable facing great loss of quantity of material. Within the case of aptamers, an exact sequence identity is essential for
technical application, though.
By use of the described technology it is now possible to produce aptamers in the range of 100 n and beyond in unmatched quality and quantity via a multi-copy-fragment (“AptaGENE”), using a combination of both in vitro and in vivo techniques.
[Reference UKL221]

Nanoparticle based on reactive Polypeptides

There are no basic technologies for nano-particles available, which are suitable for medical application. The present invention offers such a new technology, which is deal-ing with a bifid copolypeptide consisting of one hydrophilic polysarcosine and one hy-drophobic polycysteine part. The hydrophilic polysarcosine part prevents an unspecific binding on proteins, increases the solubility in the serum, and no immune reaction will be activated. Thus it is an ideal protection for encapsulated drugs.
The polycysteine part forms autonomous micelles in polar solvents, which are stabi-lized by cross linked disulphide bridges. The resulting micelles are stable in blood, in the cytosol, against glutathione and also survive endocytosis of antigen presenting cells or macrophages.
When the disulfide bonds were cleaved by metabolization, the copolymer loses its sta-bility and the active ingredient will be re-leased.

[Reference UMZ314]

MHC-independent tumor antigens for cancer immunotherapy

Cancer is still the main cause of death despite
the development of many treatment
strategies, including extensive radiation and
chemotherapy. Clinical and research results
from animal test have shown that, besides
viruses, bacteria and parasites, the T-cell
system can also recognize malignant abnormal
cells and is able to destroy those.
Especially CD8+ T-cells (cytotoxic T lymphocytes,
CTLs) can cause responses of
tumor repulsion by the recognition of antigens
that are presented on the cell surface
by Major Histocompatibility Complex Class I
molecules (MHC, in humans HLA Class I).
This invention offers the application of HLAindependent
recognition of tumorassociated
antigens for diagnosis, therapy
and prevention of melanoma and other tumor
types. Two antigens are presented that
can be recognized by CTLs independently
of HLA and whose application in cancer
immune therapy will unlock new therapy
alternatives.
[Reference HMZ077]

New Minor-HLA for the Diagnostics, Prophylaxis and Therapy of AML Patients

T lymphocytes present HLA molecules on their surface. The allogeneic transplantations of blood cells could lead either to a required graft- versus- leukaemia/ tumor reaction (GvL/T) or could result in an undesired graft-versus-Host-Disease (GvHD). If there is a complete HLA-match, these effects could result from minor histocompatibility antigens. The present invention deals with an unknown mHAg. Studies have shown that T cells from one donor, which were coincubated with leukaemia cells (homozygous for HLA- molecules), could induce specific T cell responses. Accordingly these results refer to an immunogenic mHAg. A minor- mismatch could lead to a GvH- Disease or to positive GvL reactions. In the first case a tissue typing from donor and recipient could minimize the risk of a GvHD. In the second case the preferable GvL-/ GvT- effects could be increased through a transfer of antigen specific T cells or T cell receptors by inoculation.

New Method for Reading/Writing for Magnetic Random Access Memory

Compared to conventional memory modules Magnetic memory cells have the important advantage that they do not need permanent current supply to save data, they only need current to change the information of the memory module. At present several MRAM technologies are beeing developed.
In the present memory the fact is used that on short time scales the course of the magnetization in a switching event is governed by precession. In the case of long writing pulses (e. g. >10ns) the switching properties are dominated by dissipative mechanisms, which is demonstrated in Fig. 1 by the clear boarder line between switched and non-switched regions. For shorter writing pulse durations the switching properties will be affected largely by the precessional properties of the magnetization. In particular the actual direction of the magnetization vector at pulse termination will determine the bit status stored in the memory cell. This is shown in Figs. 2 to 4, which show an increasingly more complex switching scenario with decreasing pulse duration, evidenced by the more complex boarder line between the regions of switching and non-switching.
On the basis of these ideas there have been realized a concept for an MRAM with very short switching times, which is optimized for maximum switching reliability and minimum power consumption

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