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Biomedical subjects

C C Kao

Publications and source records attributed to C C Kao.

At least 19 recordsLinked to original sources

Low-energy charge-density excitations in MgB2: Striking interplay between single-particle and collective behavior for large momenta.

A sharp feature in the charge-density excitation spectra of single-crystal MgB2, displaying a remarkable cosinelike, periodic energy dispersion with momentum transfer (q) along the c* axis, has been observed for the first time by high-resolution nonresonant inelastic x-ray scattering (NIXS). Time-dependent density-functional theory calculations show that the physics underlying the NIXS data is strong coupling between single-particle and collective degrees of freedom, mediated by large crystal local-field effects. As a result, the small-q collective mode residing in the single-particle excitation gap of the B pi bands reappears periodically in higher Brillouin zones. The NIXS data thus embody a novel signature of the layered electronic structure of MgB2.

Journal Article↗

Recombinant viral RdRps can initiate RNA synthesis from circular templates.

The crystal structure of the recombinant hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) revealed extensive interactions between the fingers and the thumb subdomains, resulting in a closed conformation with an established template channel that should specifically accept single-stranded templates. We made circularized RNA templates and found that they were efficiently used by the HCV RdRp to synthesize product RNAs that are significantly longer than the template, suggesting that RdRp could exist in an open conformation prior to template binding. RNA synthesis using circular RNA templates had properties similar to those previously documented for linear RNA, including a need for higher GTP concentration for initiation, usage of GTP analogs, sensitivity to salt, and involvement of active-site residues for product formation. Some products were resistant to challenge with the template competitor heparin, indicating that the elongation complexes remain bound to template and are competent for RNA synthesis. Other products were not elongated in the presence of heparin, indicating that the elongation complex was terminated. Lastly, recombinant RdRps from two other flaviviruses and from the Pseudomonas phage phi6 also could use circular RNA templates for RNA-dependent RNA synthesis, although the phi6 RdRp could only use circular RNAs made from the 3'-terminal sequence of the phi6 genome.

Catalytic Domain↗

Observation of structural anisotropy and the onset of liquidlike motion during the nonthermal melting of InSb.

The melting dynamics of laser excited InSb have been studied with femtosecond x-ray diffraction. These measurements observe the delayed onset of diffusive atomic motion, signaling the appearance of liquidlike dynamics. They also demonstrate that the root-mean-squared displacement in the [111] direction increases faster than in the [110] direction after the first 500 fs. This structural anisotropy indicates that the initially generated fluid differs significantly from the equilibrium liquid.

Journal Article↗

Atomic-scale visualization of inertial dynamics.

The motion of atoms on interatomic potential energy surfaces is fundamental to the dynamics of liquids and solids. An accelerator-based source of femtosecond x-ray pulses allowed us to follow directly atomic displacements on an optically modified energy landscape, leading eventually to the transition from crystalline solid to disordered liquid. We show that, to first order in time, the dynamics are inertial, and we place constraints on the shape and curvature of the transition-state potential energy surface. Our measurements point toward analogies between this nonequilibrium phase transition and the short-time dynamics intrinsic to equilibrium liquids.

Journal Article↗

Clocking femtosecond X rays.

Linear-accelerator-based sources will revolutionize ultrafast x-ray science due to their unprecedented brightness and short pulse duration. However, time-resolved studies at the resolution of the x-ray pulse duration are hampered by the inability to precisely synchronize an external laser to the accelerator. At the Sub-Picosecond Pulse Source at the Stanford Linear-Accelerator Center we solved this problem by measuring the arrival time of each high energy electron bunch with electro-optic sampling. This measurement indirectly determined the arrival time of each x-ray pulse relative to an external pump laser pulse with a time resolution of better than 60 fs rms.

Journal Article↗

Ordering of hydrogen bonds in high-pressure low-temperature H2O.

The near K-edge structure of oxygen in liquid water and ices III, II, and IX at 0.25 GPa and several low temperatures down to 4 K has been studied using inelastic x-ray scattering at 9884.7 eV with a total energy resolution of 305 and 175 meV. A marked decrease of the preedge intensity from the liquid phase and ice III to ices II and IX is attributed to ordering of the hydrogen bonds in the proton-ordered lattice of the latter phases. Density functional theory calculations including the influence of the Madelung potential of the ice IX crystal correctly account for the remaining preedge feature. Furthermore, we obtain spectroscopic evidence suggesting a possible new phase of ice at temperatures between 4 and 50 K.

Journal Article↗

Small-gap insertion-device development at the National Synchrotron Light Source--performance of the new X13 mini-gap undulator.

The National Synchrotron Light Source (NSLS) 2.8 GeV electron storage ring continues to set high standards in insertion-device research and development. The Chasman-Green NSLS lattice design provides for dispersion-free long straight sections in addition to a very small vertical beta function. As the electron beam size is proportional to the square root of this function, a program to exploit this feature was undertaken more than a decade ago by implementing short-period small-gap insertion devices in the NSLS storage ring. The possibility of utilizing existing moderate-energy synchrotron radiation electron storage rings to produce high-brightness photon beams into the harder X-ray region have been realised using in-vacuum undulators. In this article the operation of a 1.25 cm-period mini-gap undulator, operating down to a gap of 3.3 mm within the NSLS X13 straight section, is reported. It is the brightest source of hard X-rays in the energy range approximately 3.7-16 keV at the NSLS, and replaces an in-vacuum undulator which had a more limited tunability.

Crystallography, X-Ray↗

De novo initiation pocket mutations have multiple effects on hepatitis C virus RNA-dependent RNA polymerase activities.

The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) has several distinct biochemical activities, including initiation of RNA synthesis by a de novo mechanism, extension from a primed template, nontemplated nucleotide addition, and synthesis of a recombinant RNA product from two or more noncovalently linked templates (template switch). All of these activities require specific interaction with nucleoside triphosphates (NTPs). Based on the structure of the HCV RdRp bound to NTP (S. Bressanelli, L. Tomei, F. A. Rey, and R. DeFrancesco, J. Virol. 76:3482-3492, 2002), we mutated the amino acid residues that contact the putative initiation GTP and examined the effects on the various activities. Although all mutations retained the ability for primer extension, alanine substitution at R48, R158, R386, R394, or D225 decreased de novo initiation, and two or more mutations abolished de novo initiation. While the prototype enzyme had a K(m) for GTP of 3.5 microM, all of the mutations except one had K(m)s that were three- to sevenfold higher. These results demonstrate that the affected residues are functionally required to interact with the initiation nucleotide. Unexpectedly, many of the mutations also affected the addition of nontemplated nucleotide, indicating that residues in the initiating NTP (NTPi)-binding pocket are required for nontemplated nucleotide additions. Interestingly, mutations in D225 are dramatically affected in template switch, indicating that this residue of the NTPi pocket also interacts with components in the elongation complex. We also examined the interaction of ribavirin triphosphate with the NTPi-binding site.

Hepacivirus↗

Diagram X-ray emission spectra of a hollow atom: the Kh alpha1,2 and Kh beta1,3 hypersatellites of Fe.

High-resolution Fe K(h) beta(1,3) and K(h) alpha(1,2) hypersatellite spectra were measured, using monochromatized synchrotron radiation photoexcitation. The lines' energies, splitting, excitation thresholds, and the K(h) alpha(1)/K(h) alpha(2) intensity ratio were derived with high accuracy. Having both spectra, not hitherto available for any atom with high resolution, allows separating out the energy shifts of the outer levels caused by a K shell spectator vacancy. Comparison with ab initio relativistic multiconfigurational Dirac-Fock calculations reveals that while the influence of relativity and QED effects is mostly accounted for, discrepancies remain in the lines' intensity ratio, which sensitively measures the intermediacy of the coupling. Similar discrepancies, of unknown origin, are found in the energy shifts of the outer levels due to the final-state K shell spectator vacancy.

Journal Article↗

A lamellar model for the X-ray rocking curves of sagittally bent Laue crystals.

The use of sagittally bent asymmetric Laue crystals in horizontally focusing monochromators for high-energy synchrotron X-rays necessitates simulation of the X-ray reflectivity by such crystals. Based on the theory of the lattice distortion in the diffraction plane of sagittally bent Laue crystals, a lamellar model was developed to predict their rocking curves. The model was experimentally verified by rocking-curve measurements from various reflections on silicon crystals of four representative orientations, sagittally bent to various radii, using X-rays of 67 keV energy.

Journal Article↗

Rocking-curve width of sagittally bent Laue crystals.

The use of bent asymmetric Laue crystals to sagittally focus high-energy synchrotron X-rays calls for an understanding of the mechanisms affecting X-ray diffraction by such crystals. The rocking-curve width, a measurable quantity directly related to the distortion of the lattice planes, is the necessary first step towards such an understanding. A model is formulated for assessing the rocking-curve widths of sagittally bent Laue crystals, considering the elastic anisotropy. A method for depth-resolved measurement of the rocking curves was also developed to verify the model. The model successfully explains the wide range of rocking-curve widths of a large number of reflections from silicon crystals with two different orientations.

Journal Article↗

Reconstruction of magnetization density in two-dimensional samples from soft X-ray speckle patterns using the multiple-wavelength anomalous diffraction method.

A non-destructive technique for imaging magnetic domains in thin films and two-dimensional magnetic structures using coherent soft X-ray scattering and the multiple-wavelength anomalous diffraction method (MAD) is proposed. The method exploits the strong energy dependence in the magnetic scattering amplitude for 3d transition metals near the L(2,3) absorption edges and 4f elements near the M(4,5) absorption edges. The phase information required in the reconstruction algorithm is derived from the interference between the charge and magnetic scattering amplitudes. Magnetic speckle patterns from the magnetic domain distribution in an artificially defined Fe thin film are used to demonstrate this reconstruction algorithm. Circularly and linearly polarized incident light are examined separately to investigate the effect of polarization on the capability of the method.

Journal Article↗

Association between serum inflammatory cytokines and disease activity in juvenile idiopathic arthritis.

Circulating interleukin-1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNF-alpha), osteocalcin, and conventional parameters of inflammation were examined serially in 14 children with juvenile idiopathic arthritis (JIA) to determine any correlation with the disease activity. Serum IL-1beta was undetectable in all JIA patients. Serum IL-6, white blood cell counts, platelet counts, erythrocyte sedimentation rate and C-reactive protein levels were significantly elevated in the active phase of JIA, whereas hemoglobin levels were significantly lower. Osteocalcin levels were decreased and TNF-alpha increased in active JIA status, but these differences showed no statistical significance. We concluded that inflammatory cytokines play an important role in JIA. Monitoring IL-6 in children with JIA is useful in determining disease activity and response to therapy. These findings confirm earlier reports.

Adolescent↗

Development of a high-performance liquid chromatographic method for bioanalytical applications with sulpiride.

An improved HPLC method using a silica gel column with fluorescence detection (excitation at 300 nm and emission at 365 nm) was developed for the determination of sulpiride concentrations in plasma. Analysis of sulpiride in plasma samples was simplified by a one-step liquid-liquid extraction after alkaline treatment of only 1 ml of plasma. The low limit of quantitation was 20 ng/ml with a coefficient of variation of less than 20%. A linear range was found from 20 to 1500 ng/ml. This HPLC method was validated with the precision for inter-day and intra-day runs being 0.36-8.01% and 0.29-5.25%, respectively, and the accuracy (standard deviation of mean, SD) for inter-day and intra-day runs being -1.58 to 5.02% and -2.14 to 5.21%, respectively. Bioequivalence of the two products was evaluated in 12 normal healthy male volunteers in a single-dose, two-period, two-sequence, two-treatment cross-over study. Sulpiride plasma concentrations were analyzed with this validated HPLC method. Results demonstrated that the two tablet formulations of sulpiride appear to be bioequivalent.

Area Under Curve↗

De novo initiation of viral RNA-dependent RNA synthesis.

RNA viruses use several initiation strategies to ensure that their RNAs are synthesized in appropriate amounts, have correct termini, and can be translated efficiently. Many viruses with genomes of single-stranded positive-, negative-, and double-stranded RNA initiate RNA synthesis by a de novo (primer-independent) mechanism. This review summarizes biochemical features and variations of de novo initiation in viral RNA replication.

Flaviviridae↗

Completion of RNA synthesis by viral RNA replicases.

How the 5'-terminus of the template affects RNA synthesis by viral RNA replicases is poorly understood. Using short DNA, RNA and RNA-DNA chimeric templates that can direct synthesis of replicase products, we found that DNA templates tend to direct the synthesis of RNA products that are shorter by 1 nt in comparison to RNA templates. Template-length RNA synthesis was also affected by the concentration of nucleoside triphosphates, the identity of the bases at specific positions close to the 5'-terminus and the C2'-hydroxyl of a ribose at the third nucleotide from the 5'-terminal nucleotide. Similar requirements are observed with two bromoviral replicases, but not with a recombinant RNA-dependent RNA polymerase. These results begin to define the interactions needed for the viral replicase to complete synthesis of viral RNA.

Base Sequence↗

Spin-resolved NEXAFS from resonant X-ray scattering (RXS).

Resonantly excited metal K core line spectra of NiO, MnO, CoO and other compounds have been investigated at the beamlines X21 (NSLS/BNL), BW1 and W1.1 (HASYLAB/DESY). From analysis of spectral data we have drawn the following conclusions: -spin conservation is valid in the scattering process, for excitations below the absorption threshold as well as above it, -the absorption thresholds are different for spin-up and spin-down components of resonantly scattered spectra, -quadrupole transitions are very important or even crucial in the excitation process. Provided that these conclusions are true, a novel technique for quantitative resolution of NEXAFS spectra into spin-up and spin-down components has been developed. Since the method employs spin conservation and local spin references, it needs no circularly polarized radiation and no sample magnetization for taking both the RXS and NEXAFS spectra. Hence antiferromagnetic and paramagnetic materials can be investigated as well. Utilizing linear dichroism by angular-dependent measurements on single-crystal samples additional resolution of NEXAFS spectra is possible with respect to the orbital symmetry. Application of the method to paramagnetic MnO, for the first time, provides new and unambiguous experimental results confirming modern (LSDA+U) calculations: The metal K pre-edge XAS of MnO has predominantly 3d(t2g and eg) spin-down character. On the other hand, the delocalized p-like states, arising from the p-d band effect hybridization have spin-up character.

Journal Article↗

Tumor lysis syndrome in an infant with Langerhans cell histiocytosis successfully treated using continuous arteriovenous hemofiltration.

Langerhans cell histiocytosis (LCH) is an enigmatic disease usually occurring in children. Tumor lysis syndrome (TLS) is a clinical syndrome associated with severe metabolic derangement and oliguric acute renal failure. In this report, we present the clinical course of an infant with advanced LCH who had TLS develop after chemotherapy. Treatment with continuous arteriovenous hemofiltration resulted in effective control of serum uric acid, potassium, creatinine, phosphorus, and blood urea nitrogen levels in the blood.

Acute Kidney Injury↗