Picosecond x-ray studies of coherent folded acoustic phonons in a multiple quantum well.

Coherent folded acoustic phonons in a multilayered GaSb/InAs epitaxial heterostructure were generated by femtosecond laser pulses and studied by means of ultrafast x-ray diffraction. Coherent phonons excited simultaneously in the fundamental acoustic branch and the first back-folded branch were detected. This represents the first clear evidence for phonon branch folding based directly on the atomic motion to which x-ray diffraction is sensitive. From a comparison of the measured phonon-modulated x-ray reflectivity with simulations, evidence was found for a reduction of the laser penetration depth. This reduction can be explained by the self-modulation of the refractive index due to photogenerated free carriers.

Synthesis of (-)-epibatidine.

The synthesis of (-)-epibatidine has been accomplished utilizing a highly exo-selective asymmetric hetero Diels-Alder reaction. The key steps employed to transform the resulting bicycle into the natural product include a fluoride-promoted fragmentation and a Hofmann rearrangement. Reaction: see text.

Enantioselective and diastereoselective Mukaiyama-Michael reactions catalyzed by bis(oxazoline) copper(II) complexes.

The scope of highly enantioselective and diastereoselective Michael additions of enolsilanes to unsaturated imide derivatives has been developed with use of [Cu((S,S)-t-Bu-box)](SbF6)2 (1a) as a Lewis acid catalyst. The products of these additions are useful synthons that contain termini capable of differentiation under mild conditions. Michael acceptor pi-facial selectivity is consistent with two-point binding of the imide substrate and can be viewed as an extension of substrate enantioselection in the corresponding Diels-Alder reactions. A model analogous to the one employed to describe the hetero Diels-Alder reaction is proposed to account for the observed relation between enolsilane geometry and product absolute diastereocontrol. Insights into modes of catalyst inactivation are given, including spectroscopic evidence for inhibition of the catalyst by a dihydropyran intermediate that evolves during the course of the reaction. A procedure is disclosed in which an alcohol additive is used to hydrolyze the inhibiting dihydropyran and afford the desilylated Michael adduct in significantly shortened reaction time.

[Handwritten documents of 'Antidotarius magnus']. / Die Handschriften des 'Antidotarius magnus'.

The 'Antidotarius magnus'--compiled about 1080 by the archbishop of Salerno, Alphanus--deals with the pharmacological methods of healing and contains nearly 1073 antidots. We have discovered 13 Latin manuscripts of the 'Antidotarius magnus' in the libraries of Basel, Bern, Cambridge, Erfurt, Florence, London, Oxford, Paris and Parma. One should remember that the MS Taurin.I.VI.24 had been totally destroyed in 1904, but this manuscript is still noted in the catalogues of Pasin, Giacosa and Thorndike/Kibre. The most remarkable manuscript--the MS Palat.lat.747--is preserved in the National Library at Florence. The MS Palat.lat.747 is dated to 1153 and seems to be similar to the archetype. We are currently preparing a critical edition based on the oldest manuscripts.

Structure-based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors.

The inhibition of cysteine proteases is being studied as a strategy to combat parasitic diseases such as Chagas' disease, leishmaniasis, and malaria. Cruzain is the major cysteine protease of Trypanosoma cruzi, the etiologic agent of Chagas' disease. A crystal structure of cruzain, covalently inactivated by fluoromethyl ketone inhibitor 1 (Cbz-Phe-Ala-FMK), was used as a template to design potential inhibitors. Conformationally constrained gamma-lactams containing electrophilic aldehyde (12, 17, 18, 25, 26, and 29) or vinyl sulfone (43, 44, and 46) units were synthesized. Constrained lactam 26 had IC50 values of ca. 20 nM against the Leishmania major protease and ca. 50 nM versus falcipain, an important cysteine protease isolated from Plasmodium falciparum. However, all of the conformationally constrained inhibitors were weak inhibitors of cruzain, compared to unconstrained peptide aldehyde (e.g. 5 ) and vinyl sulfone inhibitors (e.g. 48, which proved to be an excellent inhibitor of cruzain with an apparent second order inhibition rate constant (k(inact)/Ki) of 634,000s(-1)M(-1). A significant reduction in activity was also observed with acyclic inhibitors 30 and 51 containing alpha-methyl phenylalanine residues at the P2 position. These data indicate that the pyrrolidinone ring, especially the quarternary center at P2, interferes with the normal substrate binding mode with cruzain, but not with falcipain or the leishmania protease.

Diffuse abdominal uptake of technetium-99m-HDP after colectomy in Gardner's syndrome.

A 37-yr-old man presented with increasing abdominal girth and multiple palpable intra-abdominal masses 3 yr after colectomy for polyposis coli. Whole-body skeletal scintigraphy performed prior to laparotomy demonstrated diffuse abdominal uptake of 99mTc-HDP consistent with mesenteric fibromatosis confirmed at surgery. When diffuse abdominal uptake of skeletal imaging agents occurs in patients with prior colectomy for polyposis coli, mesenteric fibromatosis as a manifestation of Gardner's syndrome should be suspected. This case illustrates another cause of diffuse abdominal uptake of skeletal imaging agents.

Triple-phase bone scan findings in aggressive fibromatosis. Before and after radiation therapy.

The authors present comparative triple-phase bone scan findings in three cases of histologically proven aggressive fibromatosis both before (initial evaluation) and after radiation therapy. The purpose of the study was to compare triple-phase bone scan findings in aggressive fibromatosis both before and after radiation therapy and to determine whether any additional physiological information could be obtained. Before radiation therapy, the triple-phase bone scintigraphy demonstrated increased flow and radiotracer pooling in the areas of tumors on dynamic flow and immediate blood pool images, respectively. However, the delayed static images demonstrated variable radiotracer uptake. When compared to preradiation therapy triple-phase bone scan, decreased vascularity was well demonstrated in all three patients after radiation therapy. In addition, it also provided information regarding the changes in the size and extent of tumor, noninvaded underlying bone, and remainder of the skeleton. This additional information can be particularly useful in patients with equivocal or questionable histologic diagnosis especially from small, unrepresentative biopsies.

Effect of axial load and ankle position on ankle stability.

The range of motion of 10 fresh cadaveric ankle specimens was measured for flexion, anterior-posterior drawer, inversion-eversion, and internal-external rotation under conditions that simulated normal weight-bearing. At a 70 kg load, range of motion significantly diminished in all directions (p < 0.005). Plantar flexion was diminished to a greater degree than dorsiflexion. For anterior-posterior drawer in the loaded state, ankle flexion did not play a significant role in determining stability. Factors such as ligamentous attachments may be more critical than mortise geometry in determining anterior-posterior translation. For torsion and version, stability was greatest in dorsiflexion. That ankle stability is related to articular congruity with increased load-bearing emphasizes the importance of anatomical restoration of the ankle mortise in the injury state.

Posterior malleolar ankle fractures: an in vitro biomechanical analysis of stability in the loaded and unloaded states.

The use of internal fixation for posterior malleolar fractures remains controversial. This study assessed the contribution of the posterior malleolus/posterior tibiofibular (PM/PTF) complex to ankle stability in the loaded condition. Total plantarflexion and dorsiflexion, torsion, version, and drawer were measured with 15- and 70-kg loads before and after creation of posterior malleolar fractures that measured 25% of the distal articular surface. After internal fixation, specimens were retested. Fractures caused significant increases with internal rotation and posterior drawer at 15- and 70-kg loads in the neutral position. External rotation, anterior drawer, and dorsiflexion increased at 15-kg load. Fixation increased stability of fractured specimens, but not significantly. Fractures of the PM/PTF ligament complex may lead to excessive internal rotation and posterior instability in the loaded state.

Histochemical and physiological characteristics of the rat diaphragm.

The histochemical and contractile characteristics of the adult rat diaphragm were determined. Based on enzyme histochemistry, the rat diaphragm contained 40% type I, 27% type IIa, and 34% type IIb fibers. There were significantly more type I fibers in the ventral costal (VEN) compared with the crural (CRU) region of the muscle and a slightly higher percentage of type I's on the thoracic relative to the abdominal surface. The contractile properties and the effect of temperature (Q10) were similar in the VEN and CRU regions. Increasing temperature produced higher isometric peak tetanic tension, whereas twitch tension, contraction, and one-half relaxation time all decreased. The maximal shortening velocity increased linearly from 22 and 30 degrees C, then plateaued before decreasing between 35 and 37 degrees C. The VEN and CRU force-velocity curves became less concave as temperature increased from 22 to 35 degrees C. Furthermore, the force-frequency relation of both regions was shifted to the right as temperature increased. The isometric and isotonic contractile properties and fiber type distribution are similar in the VEN and CRU regions of the diaphragm. The rat diaphragm is clearly heterogeneous in fiber type distribution and functionally lies intermediate between slow- and fast-twitch limb skeletal muscles.

Assessing the activity of sarcoidosis: quantitative 67Ga-citrate imaging.

Three different methods of quantitating 67Ga-citrate lung images--a visual index, a computer-assisted index, and the total-lung-to-background ratio--were compared in 71 studies of patients with biopsy-proven sarcoidosis. Fifty consecutive cases were analyzed independently by two different observers using all three methods. In 45 patients, both gallium lung scans and bronchoalveolar lavage were performed within 2 weeks. In these studies, each index was correlated with the cell differential in the bronchoalveolar lavage fluid. The total-lung-to-background ratio proved to be the simplest to perform; correlated best with the original visual index (r = 0.81, p less than 0.00001) and the percentage of lymphocytes obtained in bronchoalveolar lavage fluid (r = 0.39, p less than 0.004); and showed the lowest interobserver variation. Sensitivity for detecting active disease was 84% compared with 64% and 58% for the visual and computer-assisted indices, respectively, with no sacrifice in specificity.

Sequential immunization of laboratory personnel with influenza A/New Jersey/76 split- and whole-virus vaccines.

One hundred thirty-three healthy, at-risk Fort Detrick laboratory workers were inoculated with 400 chick cell-agglutinating (CCA) units of influenza A/New Jersey/76 split-virus vaccine (Wyeth Laboratories, Philadelphia, Pa.). Systemic and local reactions were infrequent, mild, and comparable to those of a sham-vaccinated group of volunteers. Only 28% of subjects 19-24 years old developed titers of hemagglutination-inhibiting (HAI) antibody of greater than or equal to 1:20, whereas titers of 91%-100% of subjects 25-62 years old reached this level. Thirty-one vaccinated subjects with no or low titers of antibody were given a booster dose (400 CCA units) of Wyeth vaccine six weeks after the first inoculation. Only 58%-67% of these vaccinees achieved HAI titers of greater than or equal to 1:20 after the booster. Fourteen persons required a second booster dose for protection; after vaccination with 400 CCA units of whole-virus vaccine from Merck Sharp and Dohme (West Point, Pa.), 89%-100% of the 14 vaccinees finally achieved HAI titers of greater than or equal to 1:20. The split-virus vaccine was safe, but it was poorly antigenic as a primary vaccine in persons 19-24 years old and as a booster in persons of all ages who have poor antibody responses in general.

[Qualitative and quantitative studies on the corpus geniculatum laterale (Cgl) of the laboratory rat. IV. Qualitative structure analysis of the pars dorsalis an on India-ink-injected Nissl preparation]. / Qualitative und quantitative Untersuchungen am Corpus geniculatum laterale (Cgl) der Laborratte IV. Quantitative Strukturanalyse der Pars dorsalis (d) am tuscheinjizierten Nissl-Präparat

1. The histological organization of the rat dorsal lateral geniculate nucleus (Cgld) has been analysed in Nissl-preparations following vessel injection with india ink. 2. The findings have been collected by means of a non-automatically visual scanning method. Every point is defined by 3 coordinates. 3. Different parameters have been collected in every point: the number of the 5 structural elements of the nervous tissue (neurons, fragments of capillaries, nuclei of astrocytes, oligodendrocytes and microglia) and the hit points per structural element. 4. In addition the differentiation of about 15500 neurons in relay neurons and interneurons has been carried out. The ratio of the 2 types of neurons is about 14:1. 5. The collected values have been statistically analysed by correlation, regression and discriminatory analyses. 6. The results relate to the correlation between the structural elements and the rostrocaudal, lateromedial and ventrodorsal directions as well as the structural elements with another. 7. At 5 levels the Cgld has been mapped on the basis of neuron size, neuron density, capillary density, density of the 3 types of glial nuclei and the relative number of hit points per structural element. 8. In the Cgld we distinguish 2 portions regarding the neuron size. The mediocellular portion occupies the lateral, ventral and caudal parts and encloses a magnocellular portion like a coat. 9. The distribution pattern of the interneurons does not correlate with the size of neurons. 10. The capillaries tend to have a greater density in the lateral area of the Cgld. 11. The correlation and regression coefficientes and the distribution pattern of the astrocytes and oligodendrocytes suggest that both glial types show a reciproke ratio in the Cgld. 12. The distribution pattern of the microglia is relatively uniform. 13. Mapping the Cgld we have got a model conception of its structural condition corresponding with the common mammalian scheme. 14. By the discriminatory analysis zones of input and fields of projection have been discriminated. It was possible to discriminate the ipsi- and contralateral input zones, but not the binocular and monocular projection fields. 15. The discriminatory analysis allows to show the collective biological effect of all structural elements in a uniform mathematical value.