Biomedical subjects

L M Adleman

Publications and source records attributed to L M Adleman.

5 recordsLinked to original sources

PubMed1999

On applying molecular computation to the data encryption standard.

Recently, Boneh, Dunworth, and Lipton (1996) described the potential use of molecular computation in attacking the United States Data Encryption Standard (DES). Here, we provide a description of such an attack using the sticker model of molecular computation. Our analysis suggests that such an attack might be mounted on a tabletop machine using approximately a gram of DNA and might succeed even in the presence of a large number of errors.

Algorithms↗

PubMed1998

A sticker-based model for DNA computation.

We introduce a new model of molecular computation that we call the sticker model. Like many previous proposals it makes use of DNA strands as the physical substrate in which information is represented and of separation by hybridization as a central mechanism. However, unlike previous models, the stickers model has a random access memory that requires no strand extension and uses no enzymes; also (at least in theory), its materials are reusable. The paper describes computation under the stickers model and discusses possible means for physically implementing each operation. Finally, we go on to propose a specific machine architecture for implementing the stickers model as a microprocessor-controlled parallel robotic workstation. In the course of this development a number of previous general concerns about molecular computation (Smith, 1996; Hartmanis, 1995; Linial et al., 1995) are addressed. First, it is clear that general-purpose algorithms can be implemented by DNA-based computers, potentially solving a wide class of search problems. Second, we find that there are challenging problems, for which only modest volumes of DNA should suffice. Third, we demonstrate that the formation and breaking of covalent bonds is not intrinsic to DNA-based computation. Fourth, we show that a single essential biotechnology, sequence-specific separation, suffices for constructing a general-purpose molecular computer. Concerns about errors in this separation operation and means to reduce them are addressed elsewhere (Karp et al., 1995; Roweis and Winfree, 1999). Despite these encouraging theoretical advances, we emphasize that substantial engineering challenges remain at almost all stages and that the ultimate success or failure of DNA computing will certainly depend on whether these challenges can be met in laboratory investigations.

Computer Simulation↗

PubMed1996

Blind T-cell homeostasis in CD4-deficient mice.

Recently, it has been proposed that normal T-cell count is maintained by a homeostatic mechanism which is "blind" to the distinction between CD4+ T cells and CD8+ T cells. Interest in this blind homeostasis hypothesis (BHH) stems in part from its implications regarding the pathogenesis and treatment of HIV infection. In this report, BHH was tested in CD4-deficient mice. We found that as predicted by BHH, despite the absence of CD4+ T cells, CD4-deficient mice maintain normal absolute T-cell counts in the blood and spleen primarily through a marked increase in CD8+ T cells. These findings provide strong new support for BHH.

Animals↗

PubMed1994

Molecular computation of solutions to combinatorial problems.

The tools of molecular biology were used to solve an instance of the directed Hamiltonian path problem. A small graph was encoded in molecules of DNA, and the "operations" of the computation were performed with standard protocols and enzymes. This experiment demonstrates the feasibility of carrying out computations at the molecular level.

Algorithms↗

PubMed1993

T-cell homeostasis: implications in HIV infection .

Evidence is presented that a homeostatic mechanism exists that maintains a normal T-cell count, but is unresponsive to abnormalities in CD4+ T-cell count and CD8+ T-cell count. Specifically, we hypothesize that in all cases of T-cell loss, whether selective or not, both CD4+ T cells and CD8+ T cells will be produced until the absolute T-cell count returns to normal, even if this produces or exacerbates abnormalities in the absolute CD4+ T-cell count and absolute CD8+ T-cell count. This hypothesis implies that the selective loss of CD4+ T cells will induce the production of both CD4+ T cells and CD8+ T cells with the result that T-cell count will return to normal, but a persistent CD8+ T-cell lymphocytosis and CD4+ T-cell lymphopenia will be produced. To test this hypothesis, we monitored T-cell reconstitution in mice selectively depleted of CD4+ T cells through treatment with a CD4-specific monoclonal antibody (mAb). Consistent with our hypothesis, the absolute peripheral blood T-cell count in treated mice returned to that of controls after approximately 4 months. However, the absolute CD8+ cell count became 163% of controls and the absolute CD4+ cell count remained less than 63% of controls. Our hypothesis may have implications regarding the pathogenesis and treatment of human immunodeficiency virus (HIV) infection. In particular, the hypothesis implies that the unresolved CD4+ T-cell lymphopenia seen in the first several years of HIV infection is the "natural" consequence of the interaction of a selective CD4+ T-cell depleting virus and a nonselective T-cell replacing homeostatic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗