Linear equivalence of certain BRM shift-register sequences

A theorem given by Albert is used to show that if a shift register of length m is used to clock another shift register of length n through a binary rate-multiplier, then it can easily be arranged that the output has a linear equivalence of (2m ? 1)n and a period of (2m ? 1)(2n ? 1).     

Accelerated nodulosis in a patient with psoriasis and arthritis during treatment with methotrexate

A 66-year-old woman with longstanding psoriasis involving the skin presented with asymmetrical polyarthritis. Methotrexate (MTX) was given initially intramuscularly and orally. Intramuscular MTX was discontinued, and a few months after she had been taking only oral MTX she developed nodules, first in surgical incisions, and subsequently in her buttocks, thighs, legs, and arms. Reduction of the dose of oral MTX was followed by gradual diminution in size of the nodules and then total disappearance.     

Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity

One of the first steps in neurogenesis is the diversification of cells along the dorsoventral axis. In Drosophila the central nervous system develops from three longitudinal columns of cells: ventral cells that express the vnd/nk2 homeobox gene, intermediate cells, and dorsal cells that express the msh homeobox gene. Here we describe a new Drosophila homeobox gene, intermediate neuroblasts defective (ind), which is expressed specifically in the intermediate column cells. ind is essential for intermediate column development: Null mutants have a transformation of intermediate to dorsal column neuroectoderm fate, and only 10% of the intermediate column neuroblasts develop. The establishment of dorsoventral column identity involves negative regulation: Vnd represses ind in the ventral column, whereas ind represses msh in the intermediate column. Vertebrate genes closely related to vnd (Nkx2.1 and Nkx2.2), ind (Gsh1 and Gsh2), and msh (Msx1 and Msx3) are expressed in corresponding ventral, intermediate, and dorsal domains during vertebrate neurogenesis, raising the possibility that dorsoventral patterning within the central nervous system is evolutionarily conserved.     

Cardiogenic oscillation phase relationships during single-breath tests performed in microgravity

We studied the phase relationships of the cardiogenic oscillations in the phase III portion of single-breath washouts (SBW) in normal gravity (1 G) and in sustained microgravity (microG). The SBW consisted of a vital capacity inspiration of 5% He-1.25% sulfurhexafluoride-balance O2, preceded at residual volume by a 150-ml Ar bolus. Pairs of gas signals, all of which still showed cardiogenic oscillations, were cross-correlated, and their phase difference was expressed as an angle. Phase relationships between inspired gases (e.g., He) and resident gas (n2) showed no change from 1 G (211 +/- 9 degrees) to microG (163 +/- 7 degrees). Ar bolus and He were unaltered between 1 G (173 +/- 15 degrees) and microG (211 +/- 25 degrees), showing that airway closure in microG remains in regions of high specific ventilation and suggesting that airway closure results from lung regions reaching low regional volume near residual volume. In contrast, CO2 reversed phase with He between 1 G (332 +/- 6 degrees) and microG (263 +/- 27 degrees), strongly suggesting that, in microG, areas of high ventilation are associated with high ventilation-perfusion ratio (VA/Q). This widening of the range of VA/Q in microG may explain previous measurements (G.K. Prisk, A.R. Elliott, H.J.B. Guy, J.M. Kosonen, and J.B. West J. Appl. Physiol. 79: 1290-1298, 1995) of an overall unaltered range of VA/Q in microG, despite more homogeneous distributions of both ventilation and perfusion.     

Insulin-like growth factor-binding protein-5 is cleaved by physiological concentrations of thrombin

Insulin-like growth factor (IGF)-binding protein-5 (IGFBP-5) is cleaved by a serine protease that is secreted by fibroblasts and porcine smooth muscle cells (pSMC) in culture. To investigate whether other serine proteases could cleave this substrate at physiologically relevant concentrations, we determined the proteolytic effects of thrombin on IGFBP-5. Human alpha-thrombin (0.0008 NIH U/ml) cleaved IGFBP-5 into 24-, 23-, and 20-kDa non-IGF-I-binding fragments. Cleavage occurred at a physiologically relevant thrombin concentration. The effect was specific for IGFBP-5, as other forms of IGFBPs, e.g. IGFBP-1, IGFBP-2, and IGFBP-4 were not cleaved by thrombin. Although IGFBP-3 was cleaved by thrombin, this effect required a 50-fold greater thrombin concentration. [35S]Methionine labeling followed by immunoprecipitation confirmed that IGFBP-5 that was constitutively synthesized by pSMC cultures was also degraded by thrombin into 24-, 23-, and 20-kDa fragments. The binding of IGF-I to IGFBP-5 partially inhibited IGFBP-5 degradation by thrombin, and an IGF analog that does not bind to IGFBP-5 had no effect. Thrombin did not account for the serine protease activity that had been shown previously to be present in pSMC-conditioned medium. This was proven by showing that 1) no immunoreactive thrombin could be detected in the pSMC-conditioned medium; 2) the IGFBP-5 fragments that were generated by thrombin showed three cleavage sites (Arg192-Ala193, Arg156-Ile157, and Lys120-His121), whereas the serine protease in conditioned medium cleaves IGFBP-5 at a different site; and 3) hirudin had no effect on IGFBP-5 cleavage by the protease in pSMC medium; however, it inhibited IGFBP-5 degradation by thrombin. To determine the physiological significance of IGFBP-5 cleavage, the effect of an IGFBP-5 mutant that is resistant to cleavage by the pSMC protease and has been shown to inhibit IGF-I actions in pSMC was determined. This mutant inhibited IGF-I-stimulated DNA synthesis, but if thrombin was added simultaneously, IGF-I was fully active. In summary, physiological concentrations of thrombin degrade IGFBP-5. Degradation can be blocked by hirudin and is partially inhibited by IGF-I binding. Generation of active thrombin in vessel walls may be a physiologically relevant mechanism for controlling IGF-I bioactivity.     

Disseminated intravascular coagulation in association with the delayed rejection of pig-to-baboon renal xenografts

BACKGROUND: Intravascular fibrin deposition and platelet sequestration occur with porcine xenograft rejection by baboons. Disseminated intravascular coagulopathy may arise either as a direct consequence of the failure to fully deplete xenoreactive natural antibodies and block complement, or because of putative cross-species molecular incompatibilities in this discordant species combination. METHODS: Three baboons were conditioned with retrovirally transduced autologous bone marrow to induce tolerance to swine antigens. Xenoreactive natural antibodies and complement were depleted by plasmapheresis and the use of Gal alpha1-3Gal column adsorptions; baboons were then splenectomized and underwent renal xenografting from inbred, miniature pigs. Soluble complement receptor type-1 with protocol immunosuppression (mycophenolate mofetil, 15-deoxyspergualin, steroids, and cyclosporine) was administered. RESULTS: A bleeding diathesis was clinically evident from days 5 to 12 after transplantation in two baboons. Low levels of circulating C3a, C3d, and iC3b were measured despite the absence of functional circulating complement components. Profound thrombocytopenia with abnormalities in keeping with disseminated intravascular coagulopathy were observed. Prolongation of prothrombin and partial thromboplastin times was accompanied by evidence for tissue factor-mediated coagulation pathways, high levels of thrombin generation (prothrombin fragment F(1+2) production and thrombin-antithrombin complex formation), fibrinogen depletion, and production of high levels of the fibrin degradation product D-dimer. Importantly, these disturbances resolved rapidly after the excision of the rejected xenografts in two surviving animals. Histopathological examination of the rejected xenografts confirmed vascular injury, fibrin deposition, platelet deposition, and localized complement activation. CONCLUSIONS: Systemic coagulation disturbances are associated with delayed xenograft rejection.     

Radiosensitivity of atomic bomb survivors as determined with a micronucleus assay

We have developed a system in which a unique double-stranded break (DSB) can be introduced into a yeast chromosome during mitotic growth. The recognition site for the endonuclease I-SceI was inserted at different places in the yeast genome in haploid and diploid cells expressing this endonuclease. Induction of the break in haploids results in cell death if no intact copy of the cleaved region is present in the cell. If such a copy is provided on a plasmid, as an ectopic gene duplication, or on a homologous chromosome, the break can be repaired. Repair results in two identical copies in the genome of the locus which has been cut. We call this phenomenon homozygotization by reference to diploids heterozygous for the cut site in which repair leads to homozygosis at this site. We have compared the efficiencies of repair in the various topological situations examined, and conclude that some mechanism must search for regions of homology to both sides of the DSB and that repair is successful only if the homologies are provided by the same template molecule.     

A study of Internet instant messaging and chat protocols

Instant messaging (IM) and network chat communication have seen an enormous rise in popularity over the last several years. However, since many of these systems are proprietary, little has been described about the network technology behind them. This analysis helps bridge this gap by providing an overview of the available features, functions, system architectures, and protocol specifications of the three most popular network IM protocols: AOL Instant Messenger, Yahoo! Messenger, and Microsoft Messenger. We describe common features across these systems and highlight distinctions between them. Where possible, we discuss the advantages and disadvantages of different technical approaches used in these systems to support different features and functions. We also briefly discuss ongoing efforts to standardize IM and chat-based protocols in IETF and other standards bodies.