Quadruple-bend achromatic low emittance lattice studies.

A quadruple-bend achromatic (QBA) cell, defined as a supercell made of two double-bend cells with different outer and inner dipole bend angles, is found to provide a factor of 2 in lowering the beam emittance relative to the more conventional double-bend achromat. The ratio of bending angles of the inner dipoles to that of the outer dipoles is numerically found to be about 1.5-1.6 for an optimal low beam emittance in the isomagnetic condition. The QBA lattice provides an advantage over the double-bend achromat or the double-bend nonachromat in performance by providing a small natural beam emittance and some zero-dispersion straight sections. A lattice with 12 QBA cells and a preliminary dynamic aperture study serves as an example.

The secondary structure of a pyrimidine-guanine sequence-specific ribonuclease possessing cytotoxic activity from the oocytes of Rana catesbeiana.

RC-RNase is a pyrimidine-guanine sequence-specific ribonuclease and a sialic-acid-binding lectin purified from Rana catesbeiana (bullfrog) oocytes. This 111-amino acid protein exhibits cytotoxicity toward several tumor cell lines. In this paper we report the assignments of proton NMR resonances and the identification of the secondary structure deduced from NOE constraints, chemical shift index, 3JNH alpha and amide proton exchange rates. The protein was directly isolated from bullfrog oocytes; we were able to assign all but five of the amino acid backbone protons of the unlabeled protein by analyzing a large set of two-dimensional proton NMR spectra obtained at several temperatures and pH conditions. Our results indicate that the structure of RC-RNase is dominated by the presence of two triple-stranded antiparallel beta-sheets and three alpha-helices, similar to those of the pyrimidine family ribonucleases. Two sets of resonances were observed for 11 amide protons and 8 alpha-protons located in the loop-1 region, an alpha 2 helix, and three beta-strands, (beta 1, beta 3 and beta 4), suggesting the presence of nonlocalized multiple conformations for RC-RNase.

The solution structure of the active domain of CAP18--a lipopolysaccharide binding protein from rabbit leukocytes.

We have employed the circular dichroism (CD) technique to characterize the solution structure of CAP18(106-137), a lipopolysaccharide (LPS) binding, antimicrobial protein, and its interaction with lipid A. Our results revealed that CAP18(106-137) may exist in at least three lipid A concentration-dependent, primarily helix conformations. The 'model' structure of CAP18(106-137) in 30% (v/v) TFE, determined by nuclear magnetic resonance (NMR) technique, was found to be a complete and very rigid helix. In this conformation, the cationic and hydrophobic groups of CAP18(106-137) are separated into patches and stripes in such a way that it can favorably interact with lipid A through either coulombic interaction with the diphosphoryl groups or hydrophobic interaction with the fatty acyl chains.

Flow linear dichroism and Fourier transform IR spectra reveal geometry for X-form DNA.

Flow linear dichroism measurements extended into the vacuum uv region yield inclinations for the base normal from the helix axis of 21 degrees for dA and 40 degrees for dT in the X-form of poly(dAdT).poly(dAdT). These inclination angles are similar to the B form of the synthetic polymer, but the axes around which the bases incline are different. Hydrogen-bonded base pairs are consistent with the geometry for the standard B, C, D, and Z forms of natural DNA, but will not fit into the A form. Fourier transform ir spectra indicate that the X form has sugar pucker and phosphate geometry similar to B-form DNA, and supports the dinucleotide repeat with two kinds of phosphates seen in earlier work, in analogy to Z-form DNA. Clearly, X-form DNA has a unique geometry.

Stacking interactions of ApA analogues with modified backbones.

CD spectra have been measured as a function of temperature for a number of ApA analogues with modified backbones. Oligonucleotides with these modified backbones are being used as antisense agents having potential as viral therapeutics. Results of these studies show that when a carbonyl is substituted for the phosphate to produce an uncharged backbone, the analogues that have either sugar or morpholino substitution do not stack. In contrast, when a morpholino group is substituted for the sugar and the phosphate is modified so as to be uncharged, there is strong base stacking. Stacking interactions in the phosphorus-linked morpholino analogues are at least as strong as those found in d(ApA). The stacking interactions in ApA are weak by comparison. Singular value decomposition demonstrates that the stacking is two state, and Taylor series decomposition yields a coefficient that measures base stacking interactions. The van't Hoff equation is applied to the base stacking coefficient from the Taylor series fitting to give thermodynamic parameters.

Mapping Z-DNA in the human genome. Computer-aided mapping reveals a nonrandom distribution of potential Z-DNA-forming sequences in human genes.

In this work, we have predicted and mapped the potential Z-DNA-forming sequences in over one million base pairs of human DNA, containing 137 complete genes. The computer program (Z-Hunt-II) developed for this study uses a rigorous thermodynamic search strategy to map the occurrence of left-handed Z-DNA in genomic sequences. The search algorithm has been optimized to search large sequences for the potential occurrence of Z-DNA, taking into account sequence type, length, and cooperativity for a given stretch of potential Z-DNA-forming nucleotides. In this extensive data set we have identified 329 potential Z-DNA-forming sequences. The exact locations of the potential Z-DNA-forming sequences in the data set have been mapped with respect to the location of structural features of the genes. This analysis reveals a distinctly nonrandom distribution of potential Z-DNA-forming sequences across human genes and, most notably, that strong Z-DNA-forming sequences are more commonly found near the 5' ends of genes. We find that 35% of the Z-DNA-forming sequences are located upstream of the first expressed exon, while only 3% of the sequences are located downstream of the last expressed exon. The remaining 62% of the Z-DNA-forming sequences, which are located either in introns (47.1%) or exons (14.9%), are also nonrandomly distributed, with a strong bias toward locations near the site of transcription initiation. We interpret this distribution of potential Z-DNA-forming sequences toward the 5' end of human genes in terms of the well established "twin-domain model" of transcription-induced supercoiling and the effect of this topological strain on Z-DNA formation in eukaryotic cells.

Critical tricuspid insufficiency due to papillary muscle rupture. A result of prenatal hypoxic insult.

Fatal tricuspid insufficiency secondary to papillary muscle rupture due to prenatal hypoxic insult occurred in a full-term newborn. The diagnosis of flail tricuspid valve should be considered when fetal distress is encountered in a newborn with persistent hypoxemia. Prenatal diagnosis of this condition combined with prompt delivery, prostaglandin E1 therapy, and possible surgical repair of the tricuspid valve may improve chances of survival.

Nerve growth factor concentration in a congenitally hypothyroid mouse model (hyt/hyt) and its responsivity to thyroxine treatment.

Earlier our laboratory reported the ontogenic profiles of serum thyroxine (T4) and triiodothyronine (T3) concentrations and nerve growth factor levels in the submandibular gland of Swiss-Webster mice. Further, we demonstrated a responsivity of submandibular gland-nerve growth factor concentrations to exogenously administered T4. To further our understanding of the interactions between thyroid hormones and submandibular gland-nerve growth factor we utilized a congenitally hypothyroid mouse model to examine submandibular gland-nerve growth factor in euthyroid, hypothyroid and hypothyroid-T4 replaced mouse pups. Serum T4 values in the congenitally hypothyroid (hyt/hyt) mice were unmeasurable and their growth in body weight, their incisor eruption, and their eyelid opening were significant delayed. Submandibular gland/body weight ratios were significantly reduced relative to control or heterozygous (+/hyt) animals through 40 days. The increase in submandibular gland-nerve growth factor concentrations observed in normal animals before 20 days was delayed to 35 days in the (hyt/hyt) animals. T4 treatment of (hyt/hyt) animals from 11 or 18 days of age significantly increased mean 40 day submandibular gland/body weight ratios and submandibular gland-nerve growth factor concentrations. However, the 40 day submandibular gland-nerve growth factor levels in treated animals remained significantly below the level of control euthyroid mice. Thus, the possibility of critical time of thyroid hormone replacement for normal submandibular gland maturation has not been shown but must be further explored in this model.

Postoperative neurosurgical infections due to bacillus species.

The cases of 2 patients with postoperative ventriculitis due to Bacillus species bacteria are presented. Bacillus licheniformis was isolated from one patient following removal of an intraventricular meningioma, and Bacillus cereus from another patient following placement of a ventriculoperitoneal shunt. Both isolates were resistant to a variety of antibiotics, but both were sensitive to gentamicin and chloramphenicol. These cases emphasize several points; (a) Bacillus species, usually thought to be nonpathogenic, may produce intracranial infections; (2) species identification is important for epidemiological purposes and for the selection of appropriate chemotherapeutic agents; and (3) in cases of suspected ventriculitis, chloramphenicol or gentamicin should be considered for Gram's staining revealing gram-positive bacilli. In addition, we recommend that when planning antibiotic prophylactic regimens, consideration should be given to including one of these agents to assure coverage of Bacillus species.