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Biomedical subjects

D Kim

Publications and source records attributed to D Kim.

At least 73 records · Page 4Linked to original sources

Probabilistic prediction in scale-free networks: diameter changes.

In complex systems, responses to small perturbations are too diverse to definitely predict how much they would be, and then such diverse responses can be predicted in a probabilistic way. Here we study such a problem in scale-free networks, for example, the diameter changes by the deletion of a single vertex for various in silico and real-world scale-free networks. We find that the diameter changes are indeed diverse and their distribution exhibits an algebraic decay with an exponent zeta asymptotically. Interestingly, the exponent zeta is robust as zeta approximately 2.2(1) for most scale-free networks and insensitive to the degree exponents gamma as long as 2<gamma</=3. However, there is another type with zeta approximately 1.7(1) and its examples include the Internet and its related in silico model.

Growth↗

Relativistic nonlinear Thomson scattering as attosecond x-ray source.

Relativistic, nonlinear Thomson scattering by an electron of an intense laser field has been investigated by computer simulation. Under a laser field with a pulse duration of 20-fs full width at half maximum and an intensity of 10(20) W/cm(2), the motion of an electron is highly relativistic and generates an ultrashort radiation of 2 as with photon energies from 100 to 600 eV. An interesting modulated structure of the spectrum is observed and analyzed. A radiation produced by the zigzag motion of an electron under a linearly polarized laser has better characteristics than by a helical motion under a circularly polarized laser pulse in terms of an angular divergence and an energy spectrum. The effect of ion field in a plasma was also investigated, which shows that for a laser intensity of 10(20) W/cm(2), the ion field due to an ion density of up to 7 x 10(18) cm(-3) can be ignored during the laser pulse.

Journal Article↗

Betweenness centrality correlation in social networks.

Scale-free (SF) networks exhibiting a power-law degree distribution can be grouped into the assortative, dissortative, and neutral networks according to the behavior of the degree-degree correlation coefficient. Here we investigate the betweenness centrality (BC) correlation for each type of SF networks. While the BC-BC correlation coefficients behave similarly to the degree-degree correlation coefficients for the dissortative and neutral networks, the BC correlation is nontrivial for the assortative ones found mainly in social networks. The mean BC of neighbors of a vertex with BC g(i) is almost independent of g(i), implying that each person is surrounded by almost the same influential environments of people no matter how influential the person may be.

Journal Article↗

Upregulation of c-Kit receptor and stem cell factor in cerebellar inhibitory synapses in response to kainic acid.

Neuronal stimulation was induced in rats by systemic administration of kainic acid (KA) to determine if such stimulation is responsible for changes in the expression patterns of c-Kit and stem cell factor (SCF) in cerebellar synapses between inhibitory interneurons and Purkinje cells. Using immunocytochemistry and immunoblotting analyses, we demonstrate that c-Kit receptor tyrosine kinase and its ligand SCF are present on the pre- and postsynaptic sides of inhibitory synapses on Purkinje cells. These proteins are upregulated during the first 48 hr after KA treatment, whereas their levels fall below that of the control by 1 week and remain as such thereafter. Expression of both c-Kit and SCF are significantly elevated in the Purkinje cell layer 24 hr after KA administration, and the Purkinje cell layer exhibits a loss of calbindin D-28K immunoreactivity. Expression of c-Kit in basket cell axon terminals is activated until 48 hr after KA treatment, suggesting the transient participation of c-Kit receptor tyrosine kinase in the maintenance of these axonal terminals. Also during the first 48 hr after KA treatment, SCF levels increase in axonal processes of Purkinje cells, and these SCF-positive axons correlate with c-Kit-positive pinceau structures. The increased expression of c-Kit and SCF in response to KA-induced neuronal stimulation may indicate that c-Kit receptor tyrosine kinase and its ligand SCF function in the inhibitory synapse between cerebellar interneurons and Purkinje cells, and that this role is most pronounced during the first 48 hr after KA treatment.

Animals↗

Ziprasidone-associated mania: a case series and review of the mechanism.

Atypical antipsychotics are now commonly used in the treatment of bipolar disorder, as they have been shown to have effects on mania as well as psychosis. Shortly after the introduction of atypical antipsychotics, several cases of associated hypomania and mania were reported. Ziprasidone is an atypical antipsychotic recently approved by the Food and Drug Administration for the treatment of psychosis. Although ziprasidone has also been shown to be effective in treating mania, it may be associated with the induction of mania or hypomania. We report four cases of mania associated with initiation of ziprasidone, which, to our knowledge, are the first reported for this drug in bipolar patients. As ziprasidone has substantial serotonergic and noradrenergic action, we hypothesize, it may more likely induce mania than other atypical antipsychotics. We advocate future studies to evaluate ziprasidone's efficacy in treating bipolar disorder and caution clinicians that induction of mania or hypomania may be possible with this agent.

Adult↗

A potential role for PTTG/securin in the developing human fetal brain.

Human securin, known also as PTTG, has established oncogenic and cell cycle regulatory functions. PTTG/securin transforms cells in vitro, inhibits sister chromatid separation, and regulates secretion of fibroblast growth factor-2. FGF-2 is a key regulator of CNS development and PTTG/securin expression has been reported in murine fetal brain. We examined the expression and function of securin and FGF-2 in the developing human fetal brain and in a fetal neuronal cell line (NT 2). Securin expression was significantly reduced in first and second trimester fetal cerebral cortex compared with adult cerebral cortex, where immunocytochemistry revealed intense securin staining in neuronal cell bodies. FGF-2 protein was concordantly lower in fetal cortex, whereas pretranslational expression of PTTG binding factor (PBF) was not significantly altered in fetal brain compared with adult. PCNA expression demonstrated that high securin levels in adult cortex were associated with absent cell proliferation. In NT-2 cells, securin stimulated FGF-2 expression, which could be abrogated by a carboxyl-terminal mutation. Low transient expression of securin resulted in a significant proliferative effect, whereas high levels of securin expression inhibited cell turnover. We propose a potential role for human PTTG/securin in modulating cell proliferation and FGF-2 expression during human neurogenesis.

Brain↗

Schizophrenia and Nogo: elevated mRNA in cortex, and high prevalence of a homozygous CAA insert.

Schizophrenia is a major psychiatric disorder which is hypothesized to result from abnormal neurodevelopment or neural changes in adulthood and possibly associated with altered gene expression. To search for genes overexpressed in schizophrenia, cDNA library subtractive hybridization experiments between post-mortem human frontal cerebral cortices from schizophrenia individuals and neurological controls were carried out. One of the genes over-expressed in schizophrenia was identified as Nogo (also known as reticulon 4, RTN4, NI 250, or RTN-X), a myelin-associated protein which inhibits the outgrowth of neurites and nerve terminals. The elevated expression of Nogo mRNA in schizophrenia was confirmed by quantitative reverse transcription-polymerase chain reaction studies: 16.5 pg Nogo cDNA/microg total RNA in schizophrenia, and 10.2 pg Nogo cDNA/microg total RNA in controls (n=7; P=0.01, t-test for n<30). To identify possible polymorphisms in this gene, the Nogo nucleotide sequence was determined in a series of schizophrenia and control samples. The Nogo mRNA was found to contain a CAA insert polymorphism in the 3'-untranslated region. The prevalence of individuals homozygous for this CAA insert was significantly higher in schizophrenia compared to controls in genomic DNA samples extracted from post-mortem brain and blood samples: 17/81 or 21% in schizophrenia and 2/61 or 3% in controls (P=0.0022, chi(2)- and Fisher's exact-tests). Because the 3'-untranslated regions of eukaryotic genes are known to regulate gene expression, the increased frequency of the Nogo CAA insert in schizophrenia may contribute to abnormal regulation of Nogo gene expression, and may indicate a role for Nogo in disturbed neurodevelopment in schizophrenia.

3' Untranslated Regions↗

Tricritical point and the doping dependence of the order of the ferromagnetic phase transition of La1-xCaxMnO3.

We report on the doping dependence of the order of the ferromagnetic metal to paramagnetic insulator phase transition in La1-xCaxMnO3. At x=0.33, magnetization and specific heat data show a first order transition, with an entropy change (2.3 J/mol K) accounted for by both volume expansion and the discontinuity of M approximately 1.7mu(B) via the Clausius-Clapeyron equation. At x=0.4, the data show a continuous transition with tricritical point exponents alpha=0.48+/-0.06, beta=0.25+/-0.03, gamma=1.03+/-0.05, and delta=5.0+/-0.8. This tricritical point separates first- (x<0.4) from second-order (x>0.4) transitions.

Journal Article↗

Fluctuation-driven dynamics of the internet topology.

We study the dynamics of the Internet topology based on empirical data on the level of the autonomous systems. It is found that the fluctuations occurring in the stochastic process of connecting and disconnecting edges are important features of the Internet dynamics. The network's overall growth can be described approximately by a single characteristic degree growth rate g(eff) approximately 0.016 and the fluctuation strength sigma(eff) approximately 0.14, together with the vertex growth rate alpha approximately 0.029. A stochastic model which incorporates these values and an adaptation rule newly introduced reproduces several features of the real Internet topology such as the correlations between the degrees of different vertices.

Internet↗

Transplantation of genetically modified cells contributes to repair and recovery from spinal injury.

The effects of transplantation of fibroblasts genetically modified to produce brain derived neurotrophin factor (Fb/BDNF) on rescue of axotomized neurons, axonal growth and recovery of function was tested in a lateral funiculus lesion model in adult rats. Operated control animals included those in which the lesion was filled with gelfoam implant (Hx) and those in which the cavity was filled with unmodified fibroblasts (Fb). Both Fb/BDNF and Fb transplants survived and filled the lesion site. Unoperated control groups showed a marked retrograde death of Red nucleus neurons contralateral to the lesion; Fb/BDNF recipients showed a significant rescue effect. Anterograde and retrograde labeling studies indicated no regeneration of rubrospinal axons into the lesion/transplant in operated control animals, but regeneration into, around, and through the transplant into the host was seen in the Fb/BDNF recipients. All animals showed deficits on the more challenging behavioral tests but the Fb/BDNF recipients showed fewer deficits, particularly in tests of spontaneous vertical exploration, horizontal rope crossing and a sensory test (patch removal). The improved function on these tests in the Fb/BDNF recipients was abolished by a second lateral funiculus lesion rostral to the transport site. These results indicate that delivery of neurotrophic factors by grafting genetically modified cells can improve repair and function after spinal injury.

Animals↗

c-myc is required for osteoclast differentiation.

The role of the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL)-a tumor necrosis factor (TNF)-related cytokine-in osteoclast formation has been established clearly. However, the downstream signaling pathways activated by this cytokine remain largely unknown. To identify genes that play a role in osteoclastogenesis, we used RAW 264.7 mouse monocytes as a model system for the differentiation of multinucleated osteoclasts from mononucleated precursors. RAW 264.7 cells were induced with RANKL to form multinucleated giant osteoclast-like cells (OCLs) that expressed a number of osteoclast-specific markers and were able to form resorption pits on both calcium phosphate films and bone slices. This system was used to identify genes that are regulated by RANKL and may play a role in osteoclast differentiation. The proto-oncogene c-myc was strongly up-regulated in RANKL-induced OCLs but was absent in undifferentiated cells. Expression of Myc partners Max and Mad, on the other hand, was constant during OCL differentiation. We expressed a dominant negative Myc in RAW 264.7 cells and were able to block RANKL-induced OCL formation. Northern Blot analysis revealed a delay and a significant reduction in the level of messenger RNA (mRNA) for tartrate-resistant acid phosphatase (TRAP) and cathepsin K. We conclude that c-myc is a downstream target of RANKL and its expression is required for RANKL-induced osteoclastogenesis.

Animals↗

Image-guided radiosurgery in the treatment of spinal metastases.

OBJECT: The authors describe a new method for treating metastatic spinal tumors in which noninvasive, image-guided, frameless stereotactic radiosurgery is performed. Stereotactic radiosurgery delivers a high dose of radiation in a single or limited number of fractions to a lesion while maintaining delivery of a low dose to adjacent normal structures. METHODS: Image-guided radiosurgery was developed by coupling an orthogonal pair of real-time x-ray cameras to a dynamically manipulated robot-mounted linear accelerator that guides the radiation beam to treatment sites associated with radiographic landmarks. This procedure can be conducted in an outpatient setting without the use of framebased skeletal fixation. The system relies on skeletal landmarks or implanted fiducial markers to locate treatment targets. Four patients with spinal metastases underwent radiosurgery with total prescription doses of 1000 to 1600 cGy in one or two fractions. Alignment of the treatment dose with the target volume was accurate to within 1.5 mm. During the course of each treatment fraction, patient movement was less than 0.5 mm on average. Dosimetry was highly conformal, with a demonstrated ability to deliver 1600 cGy to the perimeter of an irregular target volume while keeping exposure to the cord itself below 800 cGy. CONCLUSIONS: These experiences indicate that frameless radiosurgery is a viable therapeutic option for metastatic spine disease.

Aged↗

CD40 cross-linking bypasses the absolute requirement for CD4 T cells during immunization with melanoma antigen gene-modified dendritic cells.

Genetic immunization of mice with dendritic cells (DCs) engineered to express a melanoma antigen generates antigen-specific, MHC-restricted, CD4-dependent protective immune responses. We wanted to determine the role of CD4 cells and CD40 ligation of MART-1 gene-modified DC in an animal model of immunotherapy for murine melanoma. CD4 knock-out (CD4KO) or antibody-depleted mice were immunized with DC adenovirally transduced with the MART-1 gene (AdVMART1/DC) with or without CD40 cross-linking. Tumor protection was absent in CD4-depleted mice, but protection was reestablished when the CD40 receptor was engaged using three different constructs. Transduction of DCs with vectors expressing the Th1 cytokines interleukin (IL)-2, IL-7, or IL-12 could not reproduce the CD40-mediated maturation signal in this model. CD8 T-cell depletion in CD4KO mice immunized with CD40-ligated DCs abrogated the protective response. Pooled analysis of CD40 cross-linking of AdVMART1/DC administered to wild-type C57BL/6 mice revealed an overall enhancement of antitumor immunity. However, this effect was inconsistent between replicate studies. In conclusion, maturation of AdVMART1-transduced DCs through the CD40 ligation pathway can promote a protective CD8 T-cell-mediated immunity that is independent of CD4 T-cell help.

Adenoviridae↗

Universal behavior of load distribution in scale-free networks.

We study a problem of data packet transport in scale-free networks whose degree distribution follows a power law with the exponent gamma. Load, or "betweenness centrality," of a vertex is the accumulated total number of data packets passing through that vertex when every pair of vertices sends and receives a data packet along the shortest path connecting the pair. It is found that the load distribution follows a power law with the exponent delta approximately 2.2(1), insensitive to different values of gamma in the range, 2 < gamma < or = 3, and different mean degrees, which is valid for both undirected and directed cases. Thus, we conjecture that the load exponent is a universal quantity to characterize scale-free networks.

Information Services↗

Phase diagram of a disordered boson Hubbard model in two dimensions.

We study the zero-temperature phase transition of a two-dimensional disordered boson Hubbard model. The phase diagram is constructed in terms of the disorder strength and the chemical potential. Via Monte Carlo simulations, we find a multicritical line separating the weak-disorder regime, where the Mott-insulator-to-superfluid transition occurs, from the strong-disorder regime, where the Bose-glass-to-superfluid transition occurs. On the multicritical line, the insulator-to-superfluid transition has the dynamical critical exponent z = 1.35+/-0.05 and the correlation length critical exponent nu = 0.67+/-0.03. We suggest that the proliferation of the particle-hole pairs screens out the weak-disorder effects.

Journal Article↗