Kinetic resolution: a powerful tool for the synthesis of planar-chiral ferrocenes

Since the serendipitous discovery of ferrocene by Pauson and Kealy in 1951, it has become one of the most important structures in Organic Chemistry. Lately, kinetic resolution has emerged as a useful tool for the synthesis of planar chiral ferrocenes. This review aims to cover and discuss the development of this topic.

Mechanism of reduction of virus release and cell-cell fusion in persistent canine distemper virus infection.

Canine distemper virus (CDV), a mobillivirus related to measles virus causes a chronic progressive demyelinating disease, associated with persistence of the virus in the central nervous system (CNS). CNS persistence of morbilliviruses has been associated with cell-to-cell spread, thereby limiting immune detection. The mechanism of cell-to-cell spread remains uncertain. In the present study we studied viral spread comparing a cytolytic (non-persistent) and a persistent CDV strain in cell cultures. Cytolytic CDV spread in a compact concentric manner with extensive cell fusion and destruction of the monolayer. Persistent CDV exhibited a heterogeneous cell-to-cell pattern of spread without cell fusion and 100-fold reduction of infectious viral titers in supernatants as compared to the cytolytic strain. Ultrastructurally, low infectious titers correlated with limited budding of persistent CDV as compared to the cytolytic strain, which shed large numbers of viral particles. The pattern of heterogeneous cell-to-cell viral spread can be explained by low production of infectious viral particles in only few areas of the cell membrane. In this way persistent CDV only spreads to a small proportion of the cells surrounding an infected one. Our studies suggest that both cell-to-cell spread and limited production of infectious virus are related to reduced expression of fusogenic complexes in the cell membrane. Such complexes consist of a synergistic configuration of the attachment (H) and fusion (F) proteins on the cell surface. F und H proteins exhibited a marked degree of colocalization in cytolytic CDV infection but not in persistent CDV as seen by confocal laser microscopy. In addition, analysis of CDV F protein expression using vaccinia constructs of both strains revealed an additional large fraction of uncleaved fusion protein in the persistent strain. This suggests that the paucity of active fusion complexes is due to restricted intracellular processing of the viral fusion protein.

MDCT arthrography of the hip: value of the adaptive statistical iterative reconstruction technique and potential for radiation dose reduction.

OBJECTIVE: The purpose of this article is to assess the effect of the adaptive statistical iterative reconstruction (ASIR) technique on image quality in hip MDCT arthrography and to evaluate its potential for reducing radiation dose. SUBJECTS AND METHODS: Thirty-seven patients examined with hip MDCT arthrography were prospectively randomized into three different protocols: one with a regular dose (volume CT dose index [CTDIvol], 38.4 mGy) and two with a reduced dose (CTDIvol, 24.6 or 15.4 mGy). Images were reconstructed using filtered back projection (FBP) and four increasing percentages of ASIR (30%, 50%, 70%, and 90%). Image noise and contrast-to-noise ratio (CNR) were measured. Two musculoskeletal radiologists independently evaluated several anatomic structures and image quality parameters using a 4-point scale. They also jointly assessed acetabular labrum tears and articular cartilage lesions. RESULTS: With decreasing radiation dose level, image noise statistically significantly increased (p=0.0009) and CNR statistically significantly decreased (p=0.001). We also found a statistically significant reduction in noise (p=0.0001) and increase in CNR (p≤0.003) with increasing percentage of ASIR; in addition, we noted statistically significant increases in image quality scores for the labrum and cartilage, subchondral bone, overall diagnostic quality (up to 50% ASIR), and subjective noise (p≤0.04), and statistically significant reductions for the trabecular bone and muscles (p≤0.03). Regardless of the radiation dose level, there were no statistically significant differences in the detection and characterization of labral tears (n=24; p=1) and cartilage lesions (n=40; p≥0.89) depending on the ASIR percentage. CONCLUSION: The use of up to 50% ASIR in hip MDCT arthrography helps to reduce radiation dose by approximately 35-60%, while maintaining diagnostic image quality comparable to that of a regular-dose protocol using FBP.

Synthesis of Work-Zone Performance Measures, TPF-5(081), 2013

The main objective of this synthesis was to identify and summarize how agencies collect, analyze, and report different work-zone traffic-performance measures, which include exposure, mobility, and safety measures. The researchers also examined communicating performance to the public. This toolbox provides knowledge to help state departments of transportation (DOTs), as well as counties and cities, to better address reporting of work-zone performance.

Interleukin-17 is a critical mediator of vaccine-induced reduction of Helicobacter infection in the mouse model.

BACKGROUND & AIMS: Despite the proven ability of immunization to reduce Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive. This study explores the possibility that interleukin (IL)-17 plays a role in the reduction of Helicobacter infection following vaccination of wild-type animals or in spontaneous reduction of bacterial infection in IL-10-deficient mice. METHODS: In mice, reducing Helicobacter infection, the levels and source of IL-17 were determined and the role of IL-17 in reduction of Helicobacter infection was probed by neutralizing antibodies. RESULTS: Gastric IL-17 levels were strongly increased in mice mucosally immunized with urease plus cholera toxin and challenged with Helicobacter felis as compared with controls (654 +/- 455 and 34 +/- 84 relative units for IL-17 messenger RNA expression [P < .01] and 6.9 +/- 8.4 and 0.02 +/- 0.04 pg for IL-17 protein concentration [P < .01], respectively). Flow cytometry analysis showed that a peak of CD4(+)IL-17(+) T cells infiltrating the gastric mucosa occurred in immunized mice in contrast to control mice (4.7% +/- 0.3% and 1.4% +/- 0.3% [P < .01], respectively). Gastric mucosa-infiltrating CD4(+)IL-17(+) T cells were also observed in IL-10-deficient mice that spontaneously reduced H felis infection (4.3% +/- 2.3% and 2% +/- 0.6% [P < .01], for infected and noninfected IL-10-deficient mice, respectively). In wild-type immunized mice, intraperitoneal injection of anti-IL-17 antibodies significantly inhibited inflammation and the reduction of Helicobacter infection in comparison with control antibodies (1 of 12 mice vs 9 of 12 mice reduced Helicobacter infection [P < .01], respectively). CONCLUSIONS: IL-17 plays a critical role in the immunization-induced reduction of Helicobacter infection from the gastric mucosa.

Long-Life Concrete: How Long Will My Concrete Last? A Synthesis of Knowledge of Potential Durability of Concrete, TPF-5(159), 2013

There is an ongoing discussion about moving toward performance-based specifications for concrete pavements. This document seeks to move the discussion forward by outlining the needs and the challenges, and proposing some immediate actions. However, this approach may increase risk for all parties until performance requirements are agreed upon and, more importantly, how the requirements can be measured. A fundamental issue behind pavement construction activities is that the owner/designer needs to be assured that the concrete in place will survive for the intended period (assuming there are no changes in the environment or loading) and, therefore, that full payment should be made. At the same time, each party along the supply chain needs to be assured that the material being supplied to them is able to meet the required performance, as is the product/system they are delivering. The focus of this document is a discussion of the issues behind this need, and the technologies that are available, or still needed, to meet this need, particularly from the point of view of potential durability

Effects of nonhypotensive endotoxemia in conscious rats: role of prostaglandins.

A nonhypotensive dose of endotoxin was administered to normal conscious rats to evaluate the vascular and humoral effects of endotoxemia per se. Mean blood pressure and heart rate remained stable during the 45 min infusion of Escherichia coli endotoxin (0.01 mg/min). However, a marked increase in plasma renin activity (4.2 +/- 0.48 vs. 30.2 +/- 6 ng.ml-1.h-1, mean +/- SE, P less than 0.01), plasma epinephrine (0.112 +/- 0.04 vs. 1.71 +/- 0.5 ng/ml, P less than 0.01), and plasma norepinephrine (0.269 +/- 0.028 vs. 1.3 +/- 0.2 ng/ml, P less than 0.001) was observed during infusion in endotoxin-treated rats when compared with the vehicle-treated animals. In addition, the blood pressure response to exogenous norepinephrine was significantly reduced during nonhypotensive endotoxemia. Significant changes in regional blood flow distribution, as assessed by radiolabeled microspheres, were observed in endotoxemic rats; in particular a decrease in renal blood flow (7.39 +/- 0.43 vs. 5.97 +/- 0.4 ml.min-1.g-1, P less than 0.05) and an increase in coronary blood flow (5.01 +/- 0.38 vs. 6.44 +/- 0.33 ml.min-1.g-1, P less than 0.01) were found. The role of prostaglandins in the vascular and humoral alterations induced by nonhypotensive endotoxemia was also examined. Pretreatment with indomethacin (5 mg) prevented the increase in plasma renin activity as well as plasma catecholamine levels. On the contrary, the decreased vascular reactivity and the reduction in renal blood flow observed during endotoxemia were not affected by prostaglandin synthesis inhibition. Thus significant vascular and humoral changes have been found during endotoxemia even in absence of hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of scatter reduction method and monochromatic beams on image quality and dose in mammography.

In mammography, the image contrast and dose delivered to the patient are determined by the x-ray spectrum and the scatter to primary ratio S/P. Thus the quality of the mammographic procedure is highly dependent on the choice of anode and filter material and on the method used to reduce the amount of scattered radiation reaching the detector. Synchrotron radiation is a useful tool to study the effect of beam energy on the optimization of the mammographic process because it delivers a high flux of monochromatic photons. Moreover, because the beam is naturally flat collimated in one direction, a slot can be used instead of a grid for scatter reduction. We have measured the ratio S/P and the transmission factors for grids and slots for monoenergetic synchrotron radiation. In this way the effect of beam energy and scatter rejection method were separated, and their respective importance for image quality and dose analyzed. Our results show that conventional mammographic spectra are not far from optimum and that the use of a slot instead of a grid has an important effect on the optimization of the mammographic process. We propose a simple numerical model to quantify this effect.

Reduction of Concrete Deterioration by Ettringite Using Crystal Growth Inhibition Techniques, TR-431, 2001

Many researchers have concluded that secondary or delayed ettringite is responsible for serious premature deterioration of concrete highways. In some poorly performing Iowa concretes, ettringite is the most common secondary mineral but its role in premature deterioration is uncertain since some researchers still maintain that secondary ettringite does not itself cause deterioration. The current research project was designed to determine experimentally if it is possible to reduce secondary ettringite formation in concrete by treating the concrete with commercial crystallization inhibitor chemicals. The hypothesis is such that if the amount of ettringite is reduced, there will also be a concomitant reduction of concrete expansion and cracking. If both ettringite formation and deterioration are simultaneously reduced, then the case for ettringite induced expansion/cracking is strengthened. The experiment used four commercial inhibitors - two phosphonates, a polyacrylic acid, and a phosphate ester. Concrete blocks were subjected to continuous immersion, wet/dry and freeze/thaw cycling in sodium sulfate solutions and in sulfate solutions containing an inhibitor. The two phosphonate inhibitors, Dequest 2060 and Dequest 2010, manufactured by Monsanto Co., were effective in reducing ettringite nucleation and growth in concrete. Two other inhibitors, Good-rite K752 and Wayhib S were somewhat effective, but less so than the two phosphonates. Rapid experiments with solution growth inhibition of ettringite without the presence of concrete phases were used to explore the mechanisms of inhibition of this mineral. Reduction of new ettringite formation in concrete blocks also reduced expansion and cracking of the blocks. This relationship clearly links concrete expansion with this mineral - a conclusion that some research workers have disputed despite theoretical arguments for such a relationship and despite numerous observations of ettringite mineralization in prematurely deteriorated concrete highways. Secondary ettringite nucleation and growth must cause concrete expansion because the only known effect of the inhibitor chemicals is to reduce crystal nucleation and growth, and the inhibitors cannot in any other way be responsible for the reduction in expansion. The mechanism of operation of the inhibitors on ettringite reduction is not entirely clear but the solution growth experiments show that they prevent crystallization of a soluble ettringite precursor gel. The present study shows that ettringite growth alone is not responsible for expansion cracking because the experiments showed that most expansion occurs under wet/dry cycling, less under freeze/thaw cycling, and least under continuous soaking conditions. It was concluded from the different amounts of damage that water absorption by newly-formed, minute ettringite crystals is responsible for part of the observed expansion under wet/dry conditions, and that reduction of freeze resistance by ettringite filling of air-entrainment voids is also important in freeze/thaw environments.

Regulation by aldosterone of Na+,K+-ATPase mRNAs, protein synthesis, and sodium transport in cultured kidney cells.

Transepithelial Na+ reabsorption across tight epithelia is regulated by aldosterone. Mineralocorticoids modulate the expression of a number of proteins. Na+,K+-ATPase has been identified as an aldosterone-induced protein (Geering, K., M. Girardet, C. Bron, J. P. Kraehenbuhl, and B. C. Rossier, 1982, J. Biol. Chem., 257:10338-10343). Using A6 cells (kidney of Xenopus laevis) grown on filters we demonstrated by Northern blot analysis that the induction of Na+,K+-ATPase was mainly mediated by a two- to fourfold accumulation of both alpha- and beta-subunit mRNAs. The specific competitor spironolactone decreased basal Na+ transport, Na+,K+-ATPase mRNA, and the relative rate of protein biosynthesis, and it blocked the response to aldosterone. Cycloheximide inhibited the aldosterone-dependent sodium transport but did not significantly affect the cytoplasmic accumulation of Na+,K+-ATPase mRNA induced by aldosterone.

Enantioselective formal synthesis of ent-rhynchophylline and ent-isorhynchophylline

Starting from (S)-tryptophanol, a formal synthesis of ent-rhyncho-phylline and ent-isorhynchophylline, involving stereoselective cyclocondensation, spirocyclization, and alkylation reactions, and the final adjustment of the oxidation level at the oxindole and piperidine moieties, is reported.

Synthesis of triheptanoin and formulation as a solid diet for rodents

Triheptanoin-enriched diets have been successfully used in the experimental treatment of various metabolic disorders. Maximal therapeutic effect is achieved in the context of a ketogenic diet where triheptanoin oil provides 3040% of the daily caloric intake. However, pre-clinical studies using triheptanoin-rich diets are hindered by the difficulty of administering to laboratory animals as a solid foodstuff. In the present study, we successfully synthesized triheptanoin to the highest standards of purity from glycerol and heptanoic acid, using sulfonated charcoal as a catalyst. Triheptanoin oil was then formulated as a solid, stable and palatable preparation using a ketogenic base and a combination of four commercially available formulation agents: hydrophilic fumed silica, hydrophobic fumed silica, microcrystalline cellulose, and talc. Diet compliance and safety was tested on C57Bl/6 mice over a 15-week period, comparing overall status and body weight change. Practical applications: This work provides a complete description of (i) an efficient and cost-effective synthesis of triheptanoin and (ii) its formulation as a solid, stable, and palatable ketogenic diet (triheptanoin-rich; 39% of the caloric intake) for rodents. Triheptanoin-rich diets will be helpful on pre-clinical experiments testing the therapeutic efficacy of triheptanoin in different rodent models of human diseases. In addition, using the same solidification procedure, other oils could be incorporated into rodent ketogenic diet to study their dosage and long-term effects on mammal health and development. This approach could be extremely valuable as ketogenic diet is widely used clinically for epilepsy treatment.