Visualization of mitochondria with green fluorescent protein in cultured fibroblasts from patients with mitochondrial diseases

cDNAs for green fluorescent protein (GFP) and for a GFP fusion protein containing the presequence of human ornithine transcarbamylase (pOTC-GFP) were transfected into cultured human fibroblasts. GFP cDNA gave diffuse fluorescence throughout the cytoplasm and the nucleus, whereas pOTC-GFP cDNA gave mitochondria-associated fluorescence. Fluorescent mitochondrial structures could be classified into five patterns: thread-like mitochondria, fine thread-like ones, rod-like ones, granular ones, and granular ones with weak cytosolic fluorescence. pOTC-GFP mutants resulted in a loss of mitochondrial fluorescence and an appearance of weak fluorescence throughout the cytoplasm. pOTC-GFP cDNA was transfected into fibroblasts from patients with various mitochondrial diseases. Higher ratios of fibroblasts with granular mitochondria and those with fine thread-like ones were observed in a patient with Reye's syndrome and a patient with Kearns-Sayre syndrome. Weak cytosolic fluorescence was sometimes observed in fibroblasts from these patients. This method will be useful to analyze mitochondrial structural alterations and disorders of mitochondrial protein import.     

Long-term efficacy of cyclical etidronate therapy in postmenopausal osteoporosis

Sixty-two women (mean age 68.7 +/- 0.9 yr) with postmenopausal spinal osteoporosis were treated with cyclical etidronate therapy (400 mg for 2 weeks alternating with 12 weeks of 1 gm elemental calcium and 400 IU Vitamin D3) for a minimum of 2 yr. Bone mineral density (BMD) of the lumbar spine (g/cm2) increased significantly (p < 0.0001) after yr 1 (4.1 +/- 0.5 per cent) and yr 2 compared with yr 1 (2.2 +/- 0.5 per cent). The response rate was 89 per cent after yr 1 and 84 per cent after yr 2. BMD of the hip (30 patients) increased by 1.5 +/- 0.9 per cent after yr 1 and 5.5 +/- 1.1 per cent (p < 0.0001) after yr 2 when compared with baseline. The response rate was 63 per cent after yr 1 and 80 per cent after yr 2. Smaller numbers of patients continued with treatment up to 4 yr with no adverse long-term effects.     

Expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases in adenocarcinoma cell lines

The levels of mRNA expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases (GalNAc-transferases) were quantified for human adenocarcinoma cell lines from pancreas, colon, stomach, and breast. Two of the GalNAc-transferases, GalNAc-T1 and GalNAc-T2, were expressed constitutively and at low levels in most or all cell lines examined. A third GalNAc-transferase, GalNAc-T3, was differentially expressed. Well-differentiated adenocarcinoma cell lines expressed high levels and moderately differentiated cell lines expressed lower levels of GalNAc-T3. Cell lines classified as poorly differentiated failed to express GalNAc-T3 mRNA at levels that could be detected by Northern blot analysis. Differential expression of the GalNAc-T3 protein was confirmed in these cell lines by Western blotting. We propose that glycosylation in tumor cell lines may be regulated in part by differential expression of GalNAc-transferases, and we suggest that GalNAc-T3 gene expression may be a molecular indicator of differentiated adenocarcinoma.     

Differences in the yields of dicentrics and reciprocal translocations observed in the chromosomes of irradiated human skin fibroblasts and blood lymphocytes from the same healthy individuals

The modulatory role of locally produced cyclooxygenase products and endothelium-derived nitric oxide in controlling vascular tone was investigated in bovine intra-mammary artery. Vascular reactivity initiated by vasoactive compounds, endothelin-1 (ET-1), bradykinin (BK), and substance P (SP) was measured isometrically in an isolated tissue bath. The effects of a cyclooxygenase inhibitor, indomethacin (10(-5) M) and an inhibitor of nitric oxide production, N omega-Nitro L-Arginine (L-NNA: 3 x 10(-4) M) were determined during agonist-mediated responses. Indomethacin alone markedly enhanced vascular contraction produced by ET-1, while L-NNA did not. Inhibition of endothelium-derived nitric oxide synthesis by L-NNA, however, significantly attenuated BK- and SP-induced vascular relaxations, whereas indomethacin had slight influence. The potentiation between indomethacin and L-NNA in regulating vasomotor tone was not observed in this vascular bed. Thus, it appeared that both the cyclooxygenase and endothelium-derived nitric oxide pathways participated in modifying vascular reactivity. Domination of one pathway over the other depended upon the agonist used to stimulate vascular tissue.     

A unified diode model for circuit simulation

A new commercially available diode model is described. This unified model is capable of simulating the widest range of diode technologies of any presently available. The emphasis of this paper is on describing the model's extensive features and flexibility in the different domains of operation and is of particular interest in power applications     

Scientific and artistic investigation of multi-dimensional fractals on the AT & T pixel machine

The pipelined architecture and parallel organization of the AT&T Pixel Machine image computer are described and demonstrated with applications for the visualization of multidimensional fractals, particularly linear fractals and quaternion/ stacked Julia sets. Techniques for pushing the Pixel Machine to its peak abilities are described and apply to more recent parallel image computers as well.     

Constant-time parallel algorithms for image labeling on areconfigurable network of processors

A constant-time algorithm for labeling the connected components of an N×N image on a reconfigurable network of N³ processors is presented. The main contribution of the algorithm is a novel constant-time technique for determining the minimum-labeled PE in each component. The number of processors used by the algorithm can be reduced to N/sup 2+(1/d/), for any 1⩽d⩽log N, if O(d) time is allowed     

Unicast-based multicast communication in wormhole-routed networks

Multicast communication, in which the same message is delivered from a source node to an arbitrary number of destination nodes, is being increasingly demanded in parallel computing. System supported multicast services can potentially offer improved performance, increased functionality, and simplified programming, and may in turn be used to support various higher-level operations for data movement and global process control. This paper presents efficient algorithms to implement multicast communication in wormhole-routed direct networks, in the absence of hardware multicast support, by exploiting the properties of the switching technology. Minimum-time multicast algorithms are presented for n-dimensional meshes and hypercubes that use deterministic, dimension-ordered routing of unicast messages. Both algorithms can deliver a multicast message to m-1 destinations in [log ₂ m] message passing steps, while avoiding contention among the constituent unicast messages. Performance results of implementations on a 64-node nCUBE-2 hypercube and a 168-node Symult 2010 2-D mesh are given     

ConClass: a framework for real-time distributed knowledge-basedprocessing

We have developed a problem-solving framework, called ConClass, that is capable of classifying continuous real-time problems dynamically and concurrently on a distributed system. ConClass provides an efficient development environment for describing and decomposing a classification problem and synthesizing solutions. In ConClass, decomposed concurrent subproblems specified by the application developer effectively correspond to the actual distributed hardware elements. This scheme is useful for designing and implementing efficient distributed processing, making it easier to anticipate and evaluate system behavior. The ConClass system provides an object replication feature that prevents any particular object from being overloaded. In order to deal with an indeterminate amount of problem data, ConClass dynamically creates object networks that justify hypothesized solutions, and thus achieves a dynamic load distribution. A number of efficient execution mechanisms that manage a variety of asynchronous aspects of distributed processing have been implemented without using schedulers or synchronization schemes that are liable to develop bottlenecks. We have confirmed the efficiency of parallel distributed processing and load balancing of ConClass with an experimental application     

Reaching approximate agreement with mixed-mode faults

In a fault-tolerant distributed system, different non-faulty processes may arrive at different values for a given system parameter. To resolve this disagreement, processes must exchange and vote upon their respective local values. Faulty processes may attempt to inhibit agreement by acting in a malicious or “Byzantine” manner. Approximate agreement defines one form of agreement in which the voted values obtained by the non-faulty processes need not be identical. Instead, they need only agree to within a predefined tolerance. Approximate agreement can be achieved by a sequence of convergent voting rounds, in which the range of values held by non-faulty processes is reduced in each round. Historically, each new convergent voting algorithm has been accompanied by ad-hoc proofs of its convergence rate and fault-tolerance, using an overly conservative fault model in which all faults exhibit worst-case Byzantine behavior. This paper presents a general method to quickly determine convergence rate and fault-tolerance for any member of a broad family of convergent voting algorithms. This method is developed under a realistic mixed-mode fault model comprised of asymmetric, symmetric, and benign fault modes. These results are employed to more accurately analyze the properties of several existing voting algorithms, to derive a sub-family of optimal mixed-mode voting algorithms, and to quickly determine the properties of proposed new voting algorithms