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Papers by NDK 13

Archives of Virology, 1992

The glycoprotein precursor of the highly cytopathic Zairian virus HIV1-NDK synthesized in CEM leu... more The glycoprotein precursor of the highly cytopathic Zairian virus HIV1-NDK synthesized in CEM leukemic cells displayed a molecular mass of 140 kDa (gp 140) as compared to the 160 kDa of gp 160 of HIV1-LAV prototype strain. This precursor was cleaved to produce a smaller than prototype extracellular envelope glycoprotein (gp 100) and a transmembrane component with a usual size (gp 41). Immunoprecipitates from tunicamycin-treated infected cells demonstrated the presence of a non-glycosylated precursor of 100 kDa for HIV1-LAV prototype strain and 90 kDa for HIV1-NDK. Digestion of labeled precipitates with a mixture of endoglycosidase F and glycopeptidase F reduced the size of HIV1-LAV gp 160 and gp 120 to 100 and 60 kDa, respectively, while HIV1-NDK gp 140 and gp 100, after treatment with the same enzymes, displayed an apparent molecular mass of 90 kDa and 55 kDa, respectively. From these data we conclude that HIV1-LAV gp 120 and HIV1-NDK gp 100 differ both in their proteic moiety (60 kDa and 55 kDa, respectively) and in their carbohydrate moiety (60 kDa and 45 kDa, respectively). These differences could not be deduced from the available gene sequences of the two viruses. A chimeric virus containing the first 124 amino acid residues of the envelope glycoprotein coded by HIV1-LAV sequence and the rest by HIV1-NDK displayed normal size envelope glycoproteins, demonstrating the involvement of this N-terminal sequence in the alteration of the molecular mass characteristic of HIV1-NDK gp 140 and gp 100. Finally, characterization of thegag gene products from both strains demonstrated that HIV1-NDK p 18 and p 15 have a slower electrophoretic mobility as compared to its HIV1-LAV counterparts. Therefore, structural properties of HIV1-NDKenv andgag products, reflected by their unusual electrophoretic mobilities, may be responsible for HIV1-NDK biological properties.

Journal of Bacteriology, 2005

We have used direct selections to generate large numbers of mutants of Escherichia coli defective... more We have used direct selections to generate large numbers of mutants of Escherichia coli defective in the mismatch repair system and have screened these to identify mutants with temperature-sensitive defects. We detected and sequenced mutations that give rise to temperature-sensitive MutS, MutL, and MutH proteins. One mutation, mutS60, results in almost normal levels of spontaneous mutations at 37°C but above this temperature gives rise to higher and higher levels of mutations, reaching the level of null mutations in mutS at 43°C. However, at 37°C the MutS60 protein can be much more easily titrated by mispairs than the wild-type MutS, as evidenced by the impaired ability to block homeologous recombination in interspecies crosses and the increased levels of mutations from weak mutator alleles of mutD (dnaQ), mutC, and ndk. Strains with mutS60 can detect mispairs generated during replication that lead to mutation with much greater sensitivity than wild-type strains. The findings with ndk, lacking nucleotide diphosphate kinase, are striking. An ndk mutS60 strain yields four to five times the level of mutations seen in a full knockout of mutS. These results pose the question of whether similar altered Msh2 proteins result from presumed polymorphisms detected in tumor lines. The role of allele interactions in human disease susceptibility is discussed.

Activating mutations of Ras have been implicated in ϳ30% of human cancers. In every case, the bio... more Activating mutations of Ras have been implicated in ϳ30% of human cancers. In every case, the biochemical consequence of such mutations is to disrupt the GTPase activity of Ras and to render Ras resistant to the actions of GTPase activating proteins. Consequently, oncogenic Ras mutants are "locked" in a GTP-bound active state. We detected a potent activity in Escherichia coli extract that can efficiently convert mutationally activated GTP-bound Ras to the inactive GDP-bound form. Purification of the protein responsible for this activity led to the identification of the enzyme nucleoside diphosphate kinase (Ndk). The human orthologue of Ndk is the NM23 metastasis suppressor, which we found to exhibit a similar activity. Purified Ndk effectively inactivates several of the oncogenic forms of Ras that are seen frequently in human cancers, including RasD12, the most commonly detected Ras mutation. Significantly, Ndk does not detectably affect wild-type Ras or an activated form of the Ras-related Rho GTPase. These results demonstrate that it is possible, through biochemical means, to specifically inactivate oncogenic Ras as a potential therapeutic approach to tumors that harbor Ras mutations. Moreover, the results suggest that the loss of NM23 expression that is commonly observed during tumor progression could lead to increased potency of oncogenic Ras proteins.

We describe various computing techniques for tackling chessboard domination problems and apply th... more We describe various computing techniques for tackling chessboard domination problems and apply these to the determination of domination and irredundance numbers for queens' and kings' graphs. In particular we show that γ(Q 15 ) = γ(Q 16 ) = 9, confirm that γ(Q 17 ) = γ(Q 18 ) = 9, show that γ(Q 19 ) = 10, show that i(Q18) = 10, improve the bound for i(Q 19 ) to 10 ≤ i(Q 19 ) ≤ 11, show that ir(Q n ) = γ(Q n ) for 1 ≤ n ≤ 13, show that IR(Q 9 ) = Γ(Q 9 ) = 13 and that IR(Q 10 ) = Γ(Q 10 ) = 15, show that γ(Q 4k+1 ) = 2k + 1 for 16 ≤ k ≤ 21, improve the bound for i(Q 22 ) to i(Q 22 ) ≤ 12, and show that IR(K 8 ) = 17, IR(K 9 ) = 25, IR(K 10 ) = 27, and IR(K 11 ) = 36.

Journal of Bacteriology, 2000

Pseudomonas aeruginosa secretes copious amounts of an exopolysaccharide called alginate during in... more Pseudomonas aeruginosa secretes copious amounts of an exopolysaccharide called alginate during infection in the lungs of cystic fibrosis patients. A mutation in the algR2 gene of mucoid P. aeruginosa is known to exhibit a nonmucoid (nonalginate-producing) phenotype and showed reduced activities of succinyl-coenzyme A (CoA) synthetase (Scs) and nucleoside diphosphate kinase (Ndk), implying coregulation of Ndk and Scs in alginate synthesis. We have cloned and characterized the sucCD operon encoding the ␣ and ␤ subunits of Scs from P. aeruginosa and have studied the role of Scs in generating GTP, an important precursor in alginate synthesis. We demonstrate that, in the presence of GDP, Scs synthesizes GTP using ATP as the phosphodonor and, in the presence of ADP, Scs synthesizes ATP using GTP as a phosphodonor. In the presence of inorganic orthophosphate, succinyl-CoA, and an equimolar amount of ADP and GDP, Scs synthesizes essentially an equimolar amount of ATP and GTP. Such a mechanism of GTP synthesis can be an alternate source for the synthesis of alginate as well as for the synthesis of other macromolecules requiring GTP such as RNA and protein. Scs from P. aeruginosa is also shown to exhibit a broad NDP kinase activity. In the presence of inorganic orthophosphate (P i ), succinyl-CoA, and either GDP, ADP, UDP or CDP, it synthesizes GTP, ATP, UTP, or CTP. Scs was previously shown to copurify with Ndk, presumably as a complex. In mucoid cells of P. aeruginosa, Ndk is also known to exist in two forms, a 16-kDa cytoplasmic form predominant in the log phase and a 12-kDa membrane-associated form predominant in the stationary phase. We have observed that the 16-kDa Ndk-Scs complex present in nonmucoid cells, synthesizes all three of the nucleoside triphosphates from a mixture of GDP, UDP, and CDP, whereas the 12-kDa Ndk-Scs complex specifically present in mucoid cell predominantly synthesizes GTP and UTP but not CTP. Such regulation may promote GTP synthesis in the stationary phase when the bulk of alginate is synthesized by mucoid P. aeruginosa.

Journal of Graph Algorithms and Applications, 1999

This paper studies 3-D orthogonal grid drawings for graphs of arbitrary degree, in particular Kn,... more This paper studies 3-D orthogonal grid drawings for graphs of arbitrary degree, in particular Kn, with vertices drawn as boxes. It establishes asymptotic lower bounds for the volume of the bounding box and the number of bends of such drawings and exhibits a construction that achieves these bounds. No edge route in this construction bends more than three times. For drawings constrained to have at most k bends on any edge route, simple constructions are given for k = 1 and k = 2. The unconstrained construction handles the k ≥ 3 cases.

Journal of Bacteriology, 2002

Era is an essential GTPase in Escherichia coli, and Era has been implicated in a number of cellul... more Era is an essential GTPase in Escherichia coli, and Era has been implicated in a number of cellular functions. Homologues of Era have been identified in various bacteria and some eukaryotes. Using the era gene as bait in the yeast two-hybrid system to screen E. coli genomic libraries, we discovered that Era interacts with MazG, a protein of unknown function which is highly conserved among bacteria. The direct interaction between Era and MazG was also confirmed in vitro, being stronger in the presence of GDP than in the presence of GTP␥S. MazG was characterized as a nucleoside triphosphate pyrophosphohydrolase which can hydrolyze all eight of the canonical ribo-and deoxynucleoside triphosphates to their respective monophosphates and PP i , with a preference for deoxynucleotides. A mazG deletion strain of E. coli was constructed by replacing the mazG gene with a kanamycin resistance gene. Unlike mutT, a gene for another conserved nucleotide triphosphate pyrophosphohydrolase that functions as a mutator gene, the mazG deletion did not result in a mutator phenotype in E. coli.

We report the purification and characterization of a protein from the membrane fraction of Pseudo... more We report the purification and characterization of a protein from the membrane fraction of Pseudomonas aeruginosa showing intrinsic guanosine triphosphatase (GTPase) activity. The protein was purified as a 48-kDa polypeptide capable of binding and hydrolyzing GTP. The N-terminal sequence of the purified protein revealed its similarity to the Escherichia coli Ras-like protein (Era), and the protein cross-reacted with anti-Era antibodies. This protein was named Pseudomonas Ras-like protein (Pra). Anti-Pra antibodies also crossreacted with E. coli Era protein. Pra is autophosphorylated in vitro, with phosphotransfer of the terminal phosphate from [␥-32 P]GTP but not [␥-32 P]ATP. Pra is capable of complex formation with the truncated 12-kDa form of nucleoside diphosphate kinase (Ndk) but not with the 16-kDa form. Purified Pra was also shown to physically interact with pyruvate kinase (Pk); Pk and Pra can form a complex, but when the 12-kDa Ndk, Pk, and Pra are all present, Pk has a higher affinity than Pra for forming a complex with the 12-kDa Ndk.

The Electronic Journal of Combinatorics, 2006

The identification of near-duplicate keyframe (NDK) pairs is a useful task for a variety of appli... more The identification of near-duplicate keyframe (NDK) pairs is a useful task for a variety of applications such as news story threading and content-based video search. In this paper, we propose a novel approach for the discovery and tracking of NDK pairs and threads in the broadcast domain. The detection of NDKs in a large data set is a challenging task due to the fact that when the data set increases linearly, the computational cost increases in a quadratic speed, and so does the number of false alarms. This paper explores the symmetric and transitive nature of near-duplicate for the effective detection and fast tracking of NDK pairs based upon the matching of local keypoints in frames. In the detection phase, we propose a robust measure, namely pattern entropy (PE), to measure the coherency of symmetric keypoint matching across the space of two keyframes. This measure is shown to be effective in discovering the NDK identity of a frame. In the tracking phase, the NDK pairs and threads are rapidly propagated and linked with transitivity without the need of detection. This step ends up with a significant boost in speed efficiency. We evaluate our proposed approach against a month of the TRECVID-2004 broadcast videos. The experimental results indicate that our approach outperforms other techniques in terms of recall and precision with a large margin. In addition, by considering the transitivity and the underlying distribution of NDK pairs along time span, a speed-up of 3 to 5 times is achieved when keeping the performance close enough to the optimal one obtained by exhaustive evaluation.

Bag-of-words representation with visual keypoints has recently emerged as an attractive approach ... more Bag-of-words representation with visual keypoints has recently emerged as an attractive approach for video search. In this paper, we study the degree of improvement when point-to-point (P2P) constraint is imposed on the bag-of-words. We conduct investigation on two tasks: near-duplicate keyframe (NDK) retrieval, and high-level concept classification, covering parts of TRECVID 2003 and 2005 datasets. In P2P matching, we propose a one-to-one symmetric keypoint matching strategy to diminish the noise effect during keyframe comparison. In addition, a new multi-dimensional index structure is proposed to speed up the matching process with keypoint filtering. Through experiments, we demonstrate that P2P constraint can significantly boost the performance of NDK retrieval, while showing competitive accuracy in concept classification of broadcast domain.

The challenge of sampling blood from small animals has hampered the realization of quantitative s... more The challenge of sampling blood from small animals has hampered the realization of quantitative small-animal PET. Difficulties associated with the conventional blood-sampling procedure need to be overcome to facilitate the full use of this technique in mice. Methods: We developed an automated blood-sampling device on an integrated microfluidic platform to withdraw small blood samples from mice. We demonstrate the feasibility of performing quantitative small-animal PET studies using 18 F-FDG and input functions derived from the blood samples taken by the new device. 18 F-FDG kinetics in the mouse brain and myocardial tissues were analyzed. Results: The studies showed that small (;220 nL) blood samples can be taken accurately in volume and precisely in time from the mouse without direct user intervention. The total blood loss in the animal was ,0.5% of the body weight, and radiation exposure to the investigators was minimized. Good model fittings to the brain and the myocardial tissue time-activity curves were obtained when the input functions were derived from the 18 serial blood samples. The R 2 values of the curve fittings are .0.90 using a 18 F-FDG 3-compartment model and .0.99 for Patlak analysis. The 18 F-FDG rate constants K Ã 1 , k Ã 2 , k Ã 3 , and k Ã 4 , obtained for the 4 mouse brains, were comparable. The cerebral glucose metabolic rates obtained from 4 normoglycemic mice were 21.5 6 4.3 mmol/min/100 g (mean 6 SD) under the influence of 1.5% isoflurane. By generating the whole-body parametric images of K Ã FDG (mL/min/g), the uptake constant of 18 F-FDG, we obtained similar pixel values as those obtained from the conventional regional analysis using tissue time-activity curves. Conclusion: With an automated microfluidic blood-sampling device, our studies showed that quantitative small-animal PET can be performed in mice routinely, reliably, and safely in a small-animal PET facility.

Abstract Near-duplicate keyframes (NDKs) are important visual cues to link news stories from diff... more Abstract Near-duplicate keyframes (NDKs) are important visual cues to link news stories from different TV channel, time, language, etc. However, the quadratic complexity required for NDK detection renders it intractable in large-scale news video corpus. To address this ...

The Electronic Journal of Combinatorics, 2002

We study permutations that avoid two distinct patterns of length three and any additional set of ... more We study permutations that avoid two distinct patterns of length three and any additional set of patterns. We begin by showing how to enumerate these permutations using generating trees, generalizing the work of Mansour . We then find sufficient conditions for when the number of such permutations is given by a polynomial and answer a question of Egge . Afterwards, we show how to use these computations to count permutations that avoid two distinct patterns of length three and contain other patterns a prescribed number of times.

The basic problem of homotopy theory is to classify spaces and maps between spaces, up to homotop... more The basic problem of homotopy theory is to classify spaces and maps between spaces, up to homotopy, by means of invariants like cohomology. In the last decade some striking progress has been made with this problem when the spaces involved are classifying spaces of compact Lie groups. For example, it has been shown, for G connected and simple, that if two self maps of BG agree in rational cohomology then they are homotopic. It has also been shown that if a space X has the same mod p cohomology, cup product, and Steenrod operations as a classifying space BG then (at least if p is odd and G is a classical group) X is actually homotopy equivalent to BG after mod p completion. Similar methods have also been used to obtain new results on Steenrod's problem of constructing spaces with a given polynomial cohomology ring. The aim of this paper is to describe these results and the methods used to prove them.

Near-duplicate keyframes (NDK) play a unique role in large-scale video search, news topic detecti... more Near-duplicate keyframes (NDK) play a unique role in large-scale video search, news topic detection and tracking. In this paper, we propose a novel NDK retrieval approach by exploring both visual and textual cues from the visual vocabulary and semantic context respectively. The vocabulary, which provides entries for visual keywords, is formed by the clustering of local keypoints. The semantic context is inferred from the speech transcript surrounding a keyframe. We experiment the usefulness of visual keywords and semantic context, separately and jointly, using cosine similarity and language models. By linearly fusing both modalities, performance improvement is reported compared with the techniques with keypoint matching. While matching suffers from expensive computation due to the need of online nearest neighbor search, our approach is effective and efficient enough for online video search.

Genetic and epigenetic alterations are considered to play important roles in lung cancer. Recent ... more Genetic and epigenetic alterations are considered to play important roles in lung cancer. Recent studies showed that EGFR and K-RAS mutations exhibited a mutually exclusive pattern in adenocarcinoma of the lung, suggesting the presence of two independent oncogenic pathways. However, it is unknown how epigenetic alterations were involved in lung carcinogenesis mediated by EGFR or K-RAS mutation. In this study, we examined the relationship between genetic and epigenetic alterations in 164 cases of lung adenocarcinoma. Somatic mutations were determined by direct sequence of EGFR exons 18 to 21 and K-RAS codons 12 and 13. Methylation status of p16 INK4a , RASSF1A, APC, RARb , and CDH13, frequently methylated in lung cancer, was determined by methylation-specific PCR and the degree of methylation was defined as the methylation index. Multivariate analysis adjusted for age, sex, and smoking dose showed that the probability of having EGFR mutation was significantly lower among those with p16 INK4a and CDH13 methylation than in those without [ p16 INK4a : odds ratio (OR), 0.07; 95% confidence interval (95% CI), 0.02-0.33; CDH13: OR, 0.34; 95% CI, 0.15-0.77] and the methylation index was significantly lower in EGFR mutant cases than in wild type (OR, 0.70; 95% CI, 0.52-0.95). By contrast, K-RAS mutation was significantly higher in p16 INK4a methylated cases than in unmethylated cases (OR, 4.93; 95% CI,.7) and the methylation index was higher in K-RAS mutant cases than in wild type with marginal significance (OR, 1.46; 95% CI, 0.95-2.25). Our results indicate the differences in the evolvement of epigenetic alterations between the EGFR -and K-RAS-mediated tumorigenesis and suggest the specific interaction of genetic and epigenetic changes in tumorigenesis of lung cancer. (Cancer Res 2006; 66(3): 1371-5) Requests for reprints:

IEEE Transactions on Multimedia, 2007

This paper proposes a new approach for nearduplicate keyframe (NDK) identification by matching, f... more This paper proposes a new approach for nearduplicate keyframe (NDK) identification by matching, filtering and learning of local interest points (LIPs) with PCA-SIFT descriptors. The issues in matching reliability, filtering efficiency and learning flexibility are novelly exploited to delve into the potential of LIP-based retrieval and detection. In matching, we propose a one-to-one symmetric matching (OOS) algorithm which is found to be highly reliable for NDK identification, due to its capability in excluding false LIP matches compared with other matching strategies. For rapid filtering, we address two issues: speed efficiency and search effectiveness, to support OOS with a new index structure called LIP-IS. By exploring the properties of PCA-SIFT, the filtering capability and speed of LIP-IS are asymptotically estimated and compared to locality sensitive hashing (LSH). Owing to the robustness consideration, the matching of LIPs across keyframes forms vivid patterns that are utilized for discriminative learning and detection with support vector machines. Experimental results on TRECVID-2003 corpus show that our proposed approach outperforms other popular methods including the techniques with LSH in terms of retrieval and detection effectiveness. In addition, the proposed LIP-IS successfully speeds up OOS for more than 10 times and possesses several favorable properties compared to LSH.

Context. L-type ultra-cool dwarfs and brown dwarfs have cloudy atmospheres that could host weathe... more Context. L-type ultra-cool dwarfs and brown dwarfs have cloudy atmospheres that could host weather-like phenomena. The detection of photometric or spectral variability would provide insight into unresolved atmospheric heterogeneities, such as holes in a global cloud deck. Indeed, a number of ultra-cool dwarfs have been reported to vary. Additional time-resolved spectral observations of brown dwarfs offer the opportunity for further constraining and characterising atmospheric variability. Aims. It has been proposed that growth of heterogeneities in the global cloud deck may account for the L-to T-type transition when brown dwarf photospheres evolve from cloudy to clear conditions. Such a mechanism is compatible with variability. We searched for variability in the spectra of five L6 to T6 brown dwarfs to test this hypothesis. Methods. We obtained spectroscopic time series using the near-infrared spectrographs ISAAC on VLT-ANTU, over 0.99−1.13 μm, and SpeX on the Infrared Telescope Facility for two of our targets in the J, H, and K bands. We searched for statistically variable lines and for a correlation between those. Results. High spectral-frequency variations are seen in some objects, but these detections are marginal and need to be confirmed. We find no evidence of large-amplitude variations in spectral morphology and we place firm upper limits of 2 to 3% on broad-band variability, depending on the targets and wavelengths, on the time scale of a few hours. In contrast to the rest of the sample, the T2 transition brown dwarf SDSS J1254−0122 shows numerous variable features, but a secure variability diagnosis would require further observations. Conclusions. Assuming that any variability arises from the rotation of patterns of large-scale clear and cloudy regions across the surface, we find that the typical physical scale of cloud-cover disruption should be smaller than 5−8% of the disk area for four of our targets, using simplistic heterogeneous atmospheric models. The possible variations seen in SDSS J1254−0122 are not strong enough to allow us to confirm the cloud-breaking hypothesis.