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Biomedical subjects

P K Patel

Publications and source records attributed to P K Patel.

At least 19 recordsLinked to original sources

Measuring E and B fields in laser-produced plasmas with monoenergetic proton radiography.

Electromagnetic (E/B) fields generated by the interaction with plasmas of long-pulse, low-intensity laser beams relevant to inertial confinement fusion have been measured for the first time using novel monoenergetic proton radiography methods. High-resolution, time-gated radiography images of a plastic foil driven by a 10(14) W/cm(2) laser implied B fields of approximately 0.5 MG and E fields of approximately 1.5 x 10(8) V/m. Simulations of these experiments with LASNEX+LSP have been performed and are in overall (though not exact) agreement with the data both for field strengths and for spatial distributions; this is the first direct experimental test of the laser-generated B-field package in LASNEX. The experiments also demonstrated that laser phase plates substantially reduce medium-scale chaotic field structure.

Journal Article↗

Proton radiography of a laser-driven implosion.

Protons accelerated by a picosecond laser pulse have been used to radiograph a 500 microm diameter capsule, imploded with 300 J of laser light in 6 symmetrically incident beams of wavelength 1.054 microm and pulse length 1 ns. Point projection proton backlighting was used to characterize the density gradients at discrete times through the implosion. Asymmetries were diagnosed both during the early and stagnation stages of the implosion. Comparison with analytic scattering theory and simple Monte Carlo simulations were consistent with a 3+/-1 g/cm3 core with diameter 85+/-10 microm. Scaling simulations show that protons>50 MeV are required to diagnose asymmetry in ignition scale conditions.

Journal Article↗

High-repetition-rate grazing-incidence pumped x-ray laser operating at 18.9 nm.

We have demonstrated a 10 Hz Ni-like Mo x-ray laser operating at 18.9 nm with 150 mJ total pump energy by employing a novel pumping scheme. The grazing-incidence scheme is described, where a picosecond pulse is incident at a grazing angle to a Mo plasma column produced by a slab target irradiated by a 200 ps laser pulse. This scheme uses refraction of the short pulse at a predetermined electron density to increase absorption to pump a specific gain region. The higher coupling efficiency inherent to this scheme allows a reduction in the pump energy where 70 mJ long pulse energy and 80 mJ short pulse energy are sufficient to produce lasing at a 10 Hz repetition rate. Under these conditions and by optimizing the delay between the pulses, we achieve strong amplification and close to saturation for 4 mm long targets.

Journal Article↗

Multi-MeV proton source investigations in ultraintense laser-foil interactions.

A study of the properties of multi-MeV proton emission from thin foils following ultraintense laser irradiation has been carried out. It has been shown that the protons are emitted, in a quasilaminar fashion, from a region of transverse size of the order of 100-200 microm. The imaging properties of the proton source are equivalent to those of a much smaller source located several hundred microm in front of the foil. This finding has been obtained by analyzing proton radiographs of periodically structured test objects, and is corroborated by observations of proton emission from laser-heated thick targets.

Journal Article↗

Isochoric heating of solid-density matter with an ultrafast proton beam.

A new technique is described for the isochoric heating (i.e., heating at constant volume) of matter to high energy-density plasma states (>10(5) J/g) on a picosecond time scale (10(-12)sec). An intense, collimated, ultrashort-pulse beam of protons--generated by a high-intensity laser pulse--is used to isochorically heat a solid density material to a temperature of several eV. The duration of heating is shorter than the time scale for significant hydrodynamic expansion to occur; hence the material is heated to a solid density warm dense plasma state. Using spherically shaped laser targets, a focused proton beam is produced and used to heat a smaller volume to over 20 eV. The technique described of ultrafast proton heating provides a unique method for creating isochorically heated high-energy density plasma states.

Journal Article↗

Development of a computer assisted craniofacial surgery planning system.

Based upon the idea that both facial appearance and functional outcomes of the craniofacial surgery need to be predicted in the pre-surgery planning stage, a CACSP system has been established. In this system, the input is in vivo CT/MRI scan data of patient with craniofacial deformity, anatomical restoration is simulated using the medical visualization packages ANALYZE, and the finite element analysis of the masticatory system has been integrated to predict the functional improvement such as bite force alteration. Preliminary studies in this laboratory have revealed the potential of this system.

Adolescent↗

Enhancement of proton acceleration by hot-electron recirculation in thin foils irradiated by ultraintense laser pulses.

MeV-proton production from solid targets irradiated by 100-fs laser pulses at intensities above 1x10(20) W cm(-2) has been studied as a function of initial target thickness. For foils 100 microm thick the proton beam was characterized by an energy spectrum of temperature 1.4 MeV with a cutoff at 6.5 MeV. When the target thickness was reduced to 3 microm the temperature was 3.2+/-0.3 MeV with a cutoff at 24 MeV. These observations are consistent with modeling showing an enhanced density of MeV electrons at the rear surface for the thinnest targets, which predicts an increased acceleration and higher proton energies.

Journal Article↗

Finite element (FE) modeling of the mandible: from geometric model to tetrahedral volumetric mesh.

This paper presents our experience in using FE modeling of clinically relevant cases specifically in mandibular surgery. A semi-automatic procedure integrated with a group of Virtual Basic-based codes has been developed to clean the geometric models. Consequently, the time required for generate the tetrahedral volumetric mesh of mandible from patient-specific CT data has been reduced to less than 40 hours. Pre- and post-operation FE meshes are shown to be consistent and can be used for further modeling and analysis.

Computer Graphics↗

NMR structure of a 2',5' RNA favors A type duplex with compact C2'endo nucleotide repeat.

In order to provide a structural basis for the unusual properties of 2',5' nucleic acids, especially their unsuitability as information molecules, we report here a high resolution NMR structure of a 2',5' RNA fragment r(GCCGCGGC). It forms an A type duplex with C2'endo compact nucleotide repeat, instead of the familiar C3'endo compact nucleotide (seen in RNA) supporting the deductions made earlier from stereochemical considerations. This data together with the observation that 2',5' nucleic acids require mandatory slide and displacement for duplex and triplex structure formation suggest their reluctance to form the biologically relevant B type duplex. It is argued that this lack of flexibility for helical polymorphism and other inadequacies as a consequence of this may be a contributing factor for the rejection of 2',5' links by nature. The structure exhibits interesting features such as the syn glycosyl conformation for the terminal guanine and a hydrogen bond between O3' hydroxyl and anionic oxygen of the phosphate.

Base Sequence↗

Effect of plasma scale length on multi-MeV proton production by intense laser pulses.

The influence of the plasma density scale length on the production of MeV protons from thin foil targets irradiated at I lambda(2) = 5 x 10(19) W cm(-2) has been studied. With an unperturbed foil, protons with energy >20 MeV were formed in an exponential energy spectrum with a temperature of 2.5+/-0.3 MeV. When a plasma with a scale length of 100 microm was preformed on the back of the foil, the maximum proton energy was reduced to <5 MeV and the beam was essentially destroyed. The experimental results are consistent with an electrostatic accelerating mechanism that requires an ultrashort scale length at the back of the target.

Journal Article↗

Cation-dependent conformational switches in d-TGGCGGC containing two triplet repeats of Fragile X Syndrome: NMR observations.

Higher ordered structures formed by different DNA sequences have been widely investigated in recent years because of their implications in a variety of biological functions. Among these, G-quadruplexes have exhibited a great variety depending on the exact sequence, the lengths of the G-stretches, interception by other nucleotides, and environmental conditions such as pH, temperature, salt type, and its concentration. We report here interesting conformational switches observed by NMR in the sequence d-TGGCGGC containing two GGC triplet repeats related to the disease Fragile X-Syndrome. At neutral pH, the solution structure is a parallel-stranded quadruplex in presence of K(+) ions. Lowering the pH does not cause a major change in the structure; however, the chemical shift patterns of the C4 and G3 base protons suggest protonation of the C-tetrad in the center of the quadruplex. In contrast, the sequence forms an antiparallel duplex in Na(+) containing solutions. As the pH of the Na(+) sample is lowered, an equilibrium mixture of a duplex and a quadruplex appears, and at pH 2.2, the molecule exists entirely as a quadruplex. These results would be of significance from the point of view of recognition and regulation by different helicase enzymes, which have been found to discriminate between different types of quadruplex structures.

DNA↗

NMR observation of a novel C-tetrad in the structure of the SV40 repeat sequence GGGCGG.

We report the NMR structure of the DNA sequence d-TGGGCGGT in Na(+) solutions at neutral pH, containing a repeat sequence from SV40 viral genome. The structure is a novel quadruplex incorporating the C-tetrad formed by symmetrical pairing of four Cs via NH(2)&bond;O(2) H-bonds in a plane. The C-tetrad has a wider cavity compared to G-tetrads and stacks well over the adjacent G4-tetrad, but poorly on the G6 tetrad. The quadruplex helix is largely underwound by 8-10 degrees compared to B-DNA except at the C5-G6 step. To our knowledge this is the first report of C-tetrad formation in DNA structures, and would be of significance from the point of view of both structural diversity and specific recognition.

Base Sequence↗

NMR studies on truncated sequences of human telomeric DNA: observation of a novel A-tetrad.

The structure of the telomeric DNA has been a subject of extensive investigation in recent years due to the realization that it has important functional roles to play in vivo and the observations that truncated telomeric sequences exhibit a great variety of 3D structures in aqueous solutions. In this context, we describe here NMR structural studies on two truncated human telomeric DNA sequences, d-AG(3)T and d-TAG(3)T in solutions containing K(+)ions. The G(3)stretches in both the oligonucleotides were seen to form parallel-stranded quadruplexes. However, the AG(3)segment as a whole, had different structural characteristics. The structure of d-AG(3)T revealed the formation of a novel A-tetrad, which was not seen in d-TAG(3)T. The A's in the tetrad had syn glycosidic conformation as opposed to the anti conformation of the G's in the G-tetrads. The A-tetrad stacked well over the adjacent G-tetrad and the twist angle at this step was smaller in d-AG(3)T than in d-TAG(3)T. These observations are expected to be significant from the point of view of structural diversity and recognition in telomeres.

DNA↗

NMR observation of T-tetrads in a parallel stranded DNA quadruplex formed by Saccharomyces cerevisiae telomere repeats.

We report here the NMR structure of the DNA sequence d-TGGTGGC containing two repeats of Saccharomyces cerevisiae telomere DNA which is unique in that it has a single thymine in the repeat sequence and the number of Gs can vary from one to three. The structure is a novel quadruplex incor-porating T-tetrads formed by symmetrical pairing of four Ts via O4-H3 H-bonds in a plane. This is in contrast to the previous results on other telomeric sequences which contained more than one T in the repeat sequences and they were seen mostly in the flexible regions of the structures. We observed that the T4-tetrad was nicely accommodated in the center of the G-quadruplex, but it caused a small underwinding of the right handed helix. The T tetrad stacked well on the adjacent G3-tetrad, but poorly on the G5 tetrad. Likewise, T1 also formed a stable T-tetrad at the 5' end of the quadruplex. To our knowledge, this is the first report of T-tetrad formation in DNA structures. These observations are of significance from the points of view of both structural diversity and specific recognitions.

DNA, Fungal↗

The mandibular foramen: an anatomic study and its relevance to the sagittal ramus osteotomy.

The sagittal split ramus osteotomy is the most commonly used procedure to reposition the mandible surgically. Because it is more technically difficult and associated with a higher incidence of complications compared with other mandibular osteotomies, thorough knowledge of the anatomy of the mandibular ramus is a prerequisite. Anatomic measurements related to the mandibular foramen were obtained from 57 formalin-preserved non-Asian hemimandibles. As shown in previous reports, great variability was noted in the position of the mandibular foramen. However, these studies utilized Asian mandibles with a clear discrepancy in key anatomic measurements in comparison with the authors' data. This brings into question the validity of these earlier studies when applying their data to non-Asian groups. The "fade-out" point of the internal oblique ridge was found not to be a reliable anatomic reference for placement of the horizontal osteotomy along the medial ramus. Thus, familiarity with the described relationships of the mandibular foramen will assist in performing properly a sagittal split of the ramus and will reduce the chance for an unfavorable split.

Adult↗

Ectopic bone formation via rhBMP-2 delivery from porous bioabsorbable polymer scaffolds.

Drug delivery devices have received considerable interest in the field of tissue engineering due to the advent of proteins that can induce proliferation and differentiation of various cells to form specific tissues and organs, for example, bone morphogenetic protein (BMP-2) for osteogenesis. In this work the delivery of a clinically relevant bioactive factor, recombinant human rhBMP-2, was tested in vivo in a rat ectopic bone induction assay. Contact radiography and radiomorphometry showed significantly more radiopacity (1798+/-183 mm2 versus. 784+/-570 mm2 radiopaque area/g scaffold) in the BMP scaffolds than controls (p < 0.002). De novo woven bone and abundant osteoid formation were confirmed from histological sections while controls contained minimal amounts of tissue. Histomorphometry revealed significantly more bone (124+/-93 mm2 versus 7+/-12 mm2) and osteoid (72+/-43 mm2 versus 20+/-21 mm2) in the BMP implants (p < 0.001). These scaffolds demonstrated the ability to deliver viable rhBMP-2 and to induce bone formation in an ectopic site.

Absorption↗

NMR structure of the extended Myb cognate sequence and modeling studies on specific DNA-Myb complexes.

The recognition sequence of the Myb protein has been recently described to be pyAACKGHH (where py = T/C, K = G/T, and H = A/C/T), modifying the earlier identification as pyAACKG [Ording, E., et al. (1994) Eur. J. Biochem. 222, 113-120]. We had earlier determined the solution structure of the minimal cognate sequence TAACGG, choosing py = T and K = G, embeded in a 12-mer DNA duplex by NMR and related computational techniques [Radha, P. K., et al. (1995) Biochemistry 34, 5913-5912]. To understand the structural significance of the above modification and the role of the variability in the recognition sequence, we have investigated here the solution structure of a different DNA segment, d-ACAACTGCAGTTGT, which contains the extended Myb cognate site, CAACTGCA. The three-dimensional structure of the 14-mer duplex has been determined from NMR data by relaxation matrix and restrained molecular dynamics calculations. The structure of the above cognate sequence in the 14-mer duplex has been compared with that of the cognate sequence, TAACGG, in the 12-mer duplex and also with that in the NMR structure of the Myb DNA binding domain (R2R3)-DNA complex determined by Ogata et al. recently [Ogata, K., et al. (1994) Cell 79, 639-648]. The comparison highlighted differences in several structural parameters for the cognate sites in the DNA segments. Modeling studies by taking out the protein from the complex and presenting it with 12-mer and 14-mer DNA structures indicated that the protein induces structural alterations to drive the cognate site to a reasonably conserved structure. The extent of similarity of the derived structures was, however, dependent on the base sequences. Base changes in the minimal cognate sequence in the 12-mer-protein complex and in the 14-mer-protein complex so as to match the sequence of Ogata et al. produced a more conserved structure of the complex. A reverse exercise, in which the Ogata DNA in the complex was mutated to match the 12-mer and 14-mer minimal cognate sequences, complemented the above observations of the subtle sequence dependence of the structure in the complex. On the other hand, base changes in the extension did not influence the DNA-protein complex structure significantly. We also observed that the structural changes in the protein were very minor when different DNA sequences or different DNA structures were presented to it. These observations would be of interest from the point of view of DNA-Myb recognition.

Crystallography, X-Ray↗

Structural polymorphism and dynamism in the DNA segment GATCTTCCCCCCGGAA: NMR investigations of hairpin, dumbbell, nicked duplex, parallel strands, and i-motif.

Structure and dynamism in a DNA segment d-GATCTTCCCCCCGGAA have been investigated by nuclear magnetic resonance (NMR) spectroscopy. At neutral pH, the molecule exists largely as a dumbbell, formed by the association of two hairpins with sticky ends. A small percentage of hairpin is also detectable. The stem of the dumbbell, which is 12 base pairs long, has two nicks separated by 4 base pairs. The three-dimensional structures of the dumbbell and also of a 12-mer duplex, the sequence of which is identical to that of the stem of the dumbbell, have been determined by NMR in conjunction with restrained molecular dynamics calculations. It is observed that the presence of nicks causes minor changes in the structure of the duplex. Fraying at the nicks is much less than at the ends of a regular duplex. The loop shows very few nuclear Overhauser effects, which is a reflection on the greater dynamism in its structure. At lower pH, the molecule undergoes a transition to an i-motif type of structure with two parallel stranded duplexes involving C-C+ pairing, interdigitating each other. The structure is highly stable, with a melting temperature >60 degrees C.

Base Composition↗