bluuebunny/crossref_metadata_2025 huggingface dataset:
The Quantity and Quality of Life and the Evolution of World Inequality
Authors: Becker Gary S , Philipson Tomas J , Soares Rodrigo R
Published: May 2005

GDP per capita is usually used to proxy for the quality of life of individuals living in different countries. Welfare is also affected by quantity of life, however, as represented by longevity. This paper incorporates longevity into an overall assessment of the evolution of cross-country inequality and shows that it is quantitatively important. The absence of reduction in cross-country inequality up to the 1990s documented in previous work is in stark contrast to the reduction in inequality after incorporating gains in longevity. Throughout the post–World War II period, health contributed to reduce significantly welfare inequality across countries. This paper derives valuation formulas for infra-marginal changes in longevity and computes a “full” growth rate that incorporates the gains in health experienced by 96 countries for the period between 1960 and 2000. Incorporating longevity gains changes traditional results; countries starting with lower income tended to grow faster than countries starting with higher income. We estimate an average yearly growth in “full income” of 4.1 percent for the poorest 50 percent of countries in 1960, of which 1.7 percentage points are due to health, as opposed to a growth of 2.6 percent for the richest 50 percent of countries, of which only 0.4 percentage points are due to health. Additionally, we decompose changes in life expectancy into changes attributable to 13 broad groups of causes of death and three age groups. We show that mortality from infectious, respiratory, and digestive diseases, congenital, perinatal, and “ill-defined” conditions, mostly concentrated before age 20 and between ages 20 and 50, is responsible for most of the reduction in life expectancy inequality. At the same time, the recent effect of AIDS, together with reductions in mortality after age 50—due to nervous system, senses organs, heart and circulatory diseases—contributed to increase health inequality across countries.
Bond Risk Premia
Authors: Cochrane John H , Piazzesi Monika
Published: May 2005

We study time variation in expected excess bond returns. We run regressions of one-year excess returns on initial forward rates. We find that a single factor, a single tent-shaped linear combination of forward rates, predicts excess returns on one-to five-year maturity bonds with R2 up to 0.44. The return-forecasting factor is countercyclical and forecasts stock returns. An important component of the return-forecasting factor is unrelated to the level, slope, and curvature movements described by most term structure models. We document that measurement errors do not affect our central results.
Distance, Time, and Specialization: Lean Retailing in General Equilibrium
Authors: Evans Carolyn L , Harrigan James
Published: May 2005

Transport time increases with distance traveled, and time is valuable. We show the implications of these facts for global specialization and trade: products where timely delivery is important will be produced near the source of final demand, where wages will be higher as a result. In the model, timely delivery is important because it allows retailers to respond to final demand fluctuations without holding costly inventories, and timely delivery is possible only from nearby locations. Using a unique dataset that allows us to measure the retail demand for timely delivery, we show that the sources of U.S. apparel imports have shifted in the way predicted by the model, with products for which timeliness matters increasingly imported from nearby countries.
Wealth as a Determinant of Comparative Advantage
Authors: Wynne José
Published: May 2005

This paper shows that a country’s wealth can be an important determinant of comparative advantage when access to credit differs across sectors of the economy. Wealthier nations exhibit a comparative advantage toward goods produced in sectors facing more severe financial imperfections. These sectors are typically populated by small firms. Empirically this paper documents that these sectors are also labor intensive. Consequently, this theory partially offsets traditional sources of comparative advantage and offers an explanation for Trefler’s missing trade mystery and the Leontief paradox. Furthermore, the theory makes the relation between trade and income distribution endogenous.
Optimal Monetary Policy with Relative Price Distortions
Authors: Yun Tack
Published: May 2005

This paper analyzes optimal monetary policy in a sticky price model with Calvo-type staggered price-setting. In the paper, the optimal monetary policy maximizes the expected utility of a representative household without having to rely on a set of linearly approximated equilibrium conditions, given the distortions associated with the staggered price-setting. It shows that the complete stabilization of the price level is optimal in the absence of initial price dispersion, while optimal inflation targets respond to changes in the level of relative price distortion in the presence of initial price dispersion.
The Baby Boom and Baby Bust
Authors: Greenwood Jeremy , Seshadri Ananth , Vandenbroucke Guillaume
Published: May 2005

What caused the baby boom? And can it be explained within the context of the secular decline in fertility that has occurred over the last 200 years? The hypothesis is that:

(a) The secular decline in fertility is due to the relentless rise in real wages that increased the opportunity cost of having children; (b) The baby boom is explained by an atypical burst of technological progress in the household sector that occurred in the middle of the last century. This lowered the cost of having children.

A model is developed in an attempt to account, quantitatively, for both the baby boom and bust.
Financial Reform: What Shakes It? What Shapes It?
Authors: Abiad Abdul , Mody Ashoka
Published: May 2005

What accounts for the worldwide advance of financial reforms in the last quarter century? Using a new index of financial liberalization, we find that influential events shook the policy status quo. Balance-of-payments crises spurred reforms, but banking crises set liberalization back. Falling global interest rates strengthened reformers, while new governments went both ways. The overall trend toward liberalization, however, reflected pressures and incentives generated by initial reforms that raised the likelihood of additional reforms, stimulated further by the need to catch up with regional reform leaders. In contrast, ideology and country structure had limited influence.
Expression of Components of the Renin-angiotensin System in Autosomal Recessive Polycystic Kidney Disease
Authors: Loghman-Adham Mahmoud , Soto Carlos E. , Inagami Tadashi , Sotelo-Avila Cirilo
Published: May 2005

Hypertension is a common complication in children with autosomal recessive polycystic kidney disease (ARPKD) who have survived the neonatal period. No information is available regarding the mechanism of hypertension in this condition. The renin-angiotensin system (RAS) is thought to play a role in hypertension associated with the more common autosomal dominant polycystic kidney disease (ADPKD). Occasional reports have documented increased activity of the intrarenal RAS in ADPKD, with ectopic renin expression within cysts and dilated tubules. Because of similarities between ARPKD and ADPKD, we hypothesized that increased intrarenal RAS activity might also be found in ARPKD. We performed immunohistochemical studies on kidney tissues from two infants with ARPKD and two control kidneys. The cystic dilated tubules showed staining with the peanut lectin arachis hypogaea, a marker of distal tubules and collecting ducts, but not with lotus tetragonolobus, a marker of proximal tubules. Strong renin staining was seen in many cysts and tubules of ARPKD kidneys, but only in the afferent arterioles of the normal control kidneys. Angiotensinogen staining was also observed in some cysts and in proximal tubules. Staining for angiotensin-converting enzyme, angiotensin II type 1 receptor, and angiotensin II peptide was present in many cystic dilated tubules. These immunohistochemical studies document for the first time ectopic expression of components of the RAS in cystic-dilated tubules of ARPKD and suggest that overactivity of RAS could result in increased intrarenal angiotensin II production, which may contribute to the development of hypertension in ARPKD.
Depth-varying Density and Organization of Chondrocytes in Immature and Mature Bovine Articular Cartilage Assessed by 3D Imaging and Analysis
Authors: Jadin Kyle D. , Wong Benjamin L. , Bae Won C. , Li Kelvin W. , Williamson Amanda K. , Schumacher Barbara L. , Price Jeffrey H. , Sah Robert L.
Published: May 2005

Articular cartilage is a heterogeneous tissue, with cell density and organization varying with depth from the surface. The objectives of the present study were to establish a method for localizing individual cells in three-dimensional (3D) images of cartilage and quantifying depth-associated variation in cellularity and cell organization at different stages of growth. Accuracy of nucleus localization was high, with 99% sensitivity relative to manual localization. Cellularity (million cells per cm3) decreased from 290, 310, and 150 near the articular surface in fetal, calf, and adult samples, respectively, to 120, 110, and 50 at a depth of 1.0 mm. The distance/angle to the nearest neighboring cell was 7.9 μm/31°, 7.1 μm/31°, and 9.1 μm/31° for cells at the articular surface of fetal, calf, and adult samples, respectively, and increased/decreased to 11.6 μm/31°, 12.0 μm/30°, and 19.2 μm/25° at a depth of 0.7 mm. The methodologies described here may be useful for analyzing the 3D cellular organization of cartilage during growth, maturation, aging, degeneration, and regeneration.
Parathyroid Hormone-related Peptide (hPTHrP) and Parathyroid Hormone-related Peptide Receptor Type 1 (PTHR1) Expression in Human Thymus
Authors: Gessi Marco , Monego Giovanni , Lauriola Libero , Maggiano Nicola , Ranelletti Franco O.
Published: May 2005

Parathyroid hormone-related peptide (hPTHrP) is expressed in human tissues and regulates cellular proliferation, differentiation, and apoptosis by an autocrine/paracrine loop. In rodent thymus, both parathormone and parathyroid hormone-related peptide (PTHrP) are expressed by thymic epithelial cells (TECs). The present study demonstrated by RT-PCR and immunohistochemistry that hPTHrP and parathyroid hormone-related peptide receptor type 1 (PTHR1) were expressed in human thymus at both RNA and protein levels. hPTHrP was expressed mainly in the thymic medulla by epithelial (cytokeratin-positive), mature dendritic (CD40+/86+) and plasmacytoid interleukin (IL)-3Rα+ cells. This protein was also present in some cells forming Hassall's bodies and a few subcapsular and cortical TECs. PTHR1 was expressed by scattered subcapsular and cortical TECs and by rare TECs in the medulla. Thymocytes did not express either hPTHrP or PTHR1. Primary cultures of human TECs revealed the presence of both hPTHrP and PTHR1 mRNAs, confirming the capacity of TECs to synthesize both peptides. Moreover, synthetic (1–39) hPTHrP peptide administered on cultured TECs induced the expression of IL-6 mRNA, suggesting that hPTHrP can regulate thymic functions by inducing in TECs the expression of IL-6, which is involved in the development and maturation of thymocytes.
Immunocytochemical Localization of Atrial Natriuretic Peptide, Vessel Dilator, Long-acting Natriuretic Peptide, and Kaliuretic Peptide in Human Pancreatic Adenocarcinomas
Authors: Saba Sabiha R. , Garces Amanda H. , Clark Linda C. , Soto John , Gower William R. , Vesely David L.
Published: May 2005

We recently found that four peptide hormones synthesized by the same gene completely inhibit the growth of human pancreatic adenocarcinomas in athymic mice. The present immunocytochemical investigation was designed to determine where in the adenocarcinomas these peptide hormones localize. Atrial natriuretic peptide, vessel dilator, long-acting natriuretic peptide, and kaliuretic peptide localized to the cytoplasm and nucleus of the human pancreatic adenocarcinomas, which is consistent with their ability to decrease DNA synthesis in the nucleus of this cancer. In this first investigation of where these peptide hormones with anticancer effects localize in any cancer, these peptide hormones also localized to the endothelium of capillaries and fibroblasts within these cancers. This is the first demonstration of growth-inhibiting peptide hormones localizing to the nucleus, where they inhibit DNA synthesis and may interact with growth-promoting hormones that localize there as the etiology of their ability to inhibit the growth of adenocarcinomas both in vitro and in vivo.
Targeted Deletion of the SPARC Gene Accelerates Disc Degeneration in the Aging Mouse
Authors: Gruber Helen E. , Sage E. Helene , Norton H. James , Funk Sarah , Ingram Jane , Hanley Edward N.
Published: May 2005

SPARC (secreted protein, acidic, and rich in cysteine) is a matricellular protein that is present in the intervertebral disc; in man, levels of SPARC decrease with aging and degeneration. In this study, we asked whether targeted deletion of SPARC in the mouse influenced disc morphology. SPARC-null and wild-type (WT) mice were studied at 0.3–21 months of age. Radiologic examination of spines from 2-month-old SPARC-null mice revealed wedging, endplate calcification, and sclerosis, features absent in age-matched WT spines. Discs from 3-month-old SPARC-null mice had a greater number of annulus cells than those of WT animals (1884.6 ± 397.9 [mean ± SD] vs 1500.2 ± 188.2, p=0.031). By 19 months discs from SPARC-null mice contained fewer cells than WT counterparts (1383.6 ± 363.3 vs 1466.8 ± 148.0, p=0.033). Histology of midsagittal spines showed herniations of lower lumbar discs of SPARC-null mice ages 14–19 months; in contrast, no herniations were seen in WT age-matched animals. Ultrastructural studies showed uniform collagen fibril diameters in the WT annulus, whereas in SPARC-null disc fibrils were of variable size with irregular margins. Consistent with the connective tissue deficits observed in other tissues of SPARC-null mice, our findings support a fundamental role for SPARC in the production, assembly, or maintenance of the disc extracellular matrix.
Carbon Dioxide Thermal Decomposition: Observation of Incubation
Authors: Oehlschlaeger Matthew A. , Davidson David F. , Jeffries Jay B. , Hanson Ronald K.
Published: May 2005

Incubation prior to the thermal decomposition of CO2 is observed for the first time behind shock waves, confirming the expected bottleneck in collisional activation of this triatomic molecule. The thermal decomposition of carbon dioxide has been investigated behind reflected shock waves at temperatures of 3200–4600 K and pressures of 45–100 kPa. Ultraviolet laser absorption was used to monitor the CO2 concentration with microsecond time resolution, allowing observation of a pronounced incubation period prior to steady CO2 dissociation. Master equation simulations, with a simple model for collisional energy transfer, were carried out to describe the measured incubation times and dissociation rate coefficient. The second order rate coefficient for CO2 dissociation was found to be 3.14 × 1014 exp(−51300 K/T) cm3 mol−1 s−1. The number of incubation collisions was found to range from 7 × 103 at 4600 K to 3.5 × 104 at 3200 K. The master equation simulations suggest that the energy transferred per collision must have a greater than linear dependence on energy.
Combination of Laser- and Mass-Spectroscopic Techniques for the Investigation of Fuel-Rich Flames
Authors: Kohse-Höinghaus Katharina , Schocker Alexander , Kasper Tina , Kamphus Michael , Brockhinke Andreas
Published: May 2005

Soot is one of the most important pollutants originating from combustion. Despite recent advances in the measurement of size and composition of soot particles, their actual formation mechanism is still under debate. It depends on fuel, stoichiometry, temperature, flow conditions and the concentration of a large number of intermediate species. An adequate characterization of this complex reaction system generally requires the use of several complementary techniques.

In this article, we present measurements aiming to study reactions in fuel-rich flames using several complementary techniques. Only with a combination of optical and mass-spectrometric measurements, important features of the early polyaromatic hydrocarbon (PAH) and soot formation chemistry are accessible in detail. Three different techniques are combined to investigate one-dimensional laboratory flames on the same low-pressure burner and their respective merits are discussed: (i) cavity ring-down spectroscopy (CRDS) for the detection of small radicals and measurement of the temperature, (ii) mass spectrometry with electron-impact (EI) ionization in order to measure species with molecular weights up to m/e = 90, and (iii) mass spectrometry with resonantly-enhanced multi-photon ionization (REMPI) to distinguish isomers with masses up to m/e = 178. Measurements of this type may prove a valuable input to improve kinetic and combustion models.
High-Growth-Rate Chemical Vapor Deposition of Silicon: an Experimental and Modeling Approach
Authors: Atakan Burak , Hofstätter Michael , Kohse-Höinghaus Katharina
Published: May 2005

The chemical vapor deposition (CVD) process of silicon from silane has been analyzed by a combined experimental and modeling approach with the aim to optimize growth rate, yield and deposition quality of polycystalline silicon while minimizing gas phase nucleation. The effects of precursor concentration, flow rate and buffer gas have been investigated. Modeling of the gas phase and of the deposition process has been used in a parameter screening to select appropriate deposition conditions in a stagnation-point cold-wall CVD reactor. Deposition experiments have been performed for several silane concentrations with helium, nitrogen and hydrogen as the buffer gases. Polycrystalline films of good quality were obtained with growth rates up to 8 μm/min. The observed trends in the experiments are in good qualitative agreement with model predictions. To achieve high film growth rates and minimal gas phase nucleation, hydrogen is suggested as the diluent gas, potential reasons for this being its involvement in gas phase and surface reactions.
A Composite-Likelihood Approach for Detecting Directional Selection From DNA Sequence Data
Authors: Zhu Lan , Bustamante Carlos D
Published: May 2005

We present a novel composite-likelihood-ratio test (CLRT) for detecting genes and genomic regions that are subject to recurrent natural selection (either positive or negative). The method uses the likelihood functions of Hartl et al. (1994) for inference in a Wright-Fisher genic selection model and corrects for nonindependence among sites by application of coalescent simulations with recombination. Here, we (1) characterize the distribution of the CLRT statistic (Λ) as a function of the population recombination rate (R = 4Ner); (2) explore the effects of bias in estimation of R on the size (type I error) of the CLRT; (3) explore the robustness of the model to population growth, bottlenecks, and migration; (4) explore the power of the CLRT under varying levels of mutation, selection, and recombination; (5) explore the discriminatory power of the test in distinguishing negative selection from population growth; and (6) evaluate the performance of maximum composite-likelihood estimation (MCLE) of the selection coefficient. We find that the test has excellent power to detect weak negative selection and moderate power to detect positive selection. Moreover, the test is quite robust to bias in the estimate of local recombination rate, but not to certain demographic scenarios such as population growth or a recent bottleneck. Last, we demonstrate that the MCLE of the selection parameter has little bias for weak negative selection and has downward bias for positively selected mutations.
Quantitative Trait Locus Analysis Using Recombinant Inbred Intercrosses
Authors: Zou Fei , Gelfond Jonathan A L , Airey David C , Lu Lu , Manly Kenneth F , Williams Robert W , Threadgill David W
Published: May 2005

We describe a new approach, called recombinant inbred intercross (RIX) mapping, that extends the power of recombinant inbred (RI) lines to provide sensitive detection of quantitative trait loci (QTL) responsible for complex genetic and nongenetic interactions. RIXs are generated by producing F1 hybrids between all or a subset of parental RI lines. By dramatically extending the number of unique, reproducible genomes, RIXs share some of the best properties of both the parental RI and F2 mapping panels. These attributes make the RIX method ideally suited for experiments requiring analysis of multiple parameters, under different environmental conditions and/or temporal sampling. However, since any pair of RIX genomes shares either one or no parental RIs, this cross introduces an unusual population structure requiring special computational approaches for analysis. Herein, we propose an efficient statistical procedure for QTL mapping with RIXs and describe a novel empirical permutation procedure to assess genome-wide significance. This procedure will also be applicable to diallel crosses. Extensive simulations using strain distribution patterns from CXB, AXB/BXA, and BXD mouse RI lines show the theoretical power of the RIX approach and the analysis of CXB RIXs demonstrates the limitations of this procedure when using small RI panels.
The Coupon Collector and the Suppressor Mutation
Authors: Poon Art , Davis Bradley H , Chao Lin
Published: May 2005

Compensatory mutation occurs when a loss of fitness caused by a deleterious mutation is restored by its epistatic interaction with a second mutation at a different site in the genome. How many different compensatory mutations can act on a given deleterious mutation? Although this quantity is fundamentally important to understanding the evolutionary consequence of mutation and the genetic complexity of adaptation, it remains poorly understood. To determine the shape of the statistical distribution for the number of compensatory mutations per deleterious mutation, we have performed a maximum-likelihood analysis of experimental data collected from the suppressor mutation literature. Suppressor mutations are used widely to assess protein interactions and are under certain conditions equivalent to compensatory mutations. By comparing the maximum likelihood of a variety of candidate distribution functions, we established that an L-shaped gamma distribution (α = 0.564, θ = 21.01) is the most successful at explaining the collected data. This distribution predicts an average of 11.8 compensatory mutations per deleterious mutation. Furthermore, the success of the L-shaped gamma distribution is robust to variation in mutation rates among sites. We have detected significant differences among viral, prokaryotic, and eukaryotic data subsets in the number of compensatory mutations and also in the proportion of compensatory mutations that are intragenic. This is the first attempt to characterize the overall diversity of compensatory mutations, identifying a consistent and accurate prior distribution of compensatory mutation diversity for theoretical evolutionary models.
Efficiency of the Use of Pedigree and Molecular Marker Information in Conservation Programs
Authors: Fernández Jesús , Villanueva Beatriz , Pong-Wong Ricardo , Toro Miguel Ángel
Published: May 2005

The value of molecular markers and pedigree records, separately or in combination, to assist in the management of conserved populations has been tested. The general strategy for managing the population was to optimize contributions of parents to the next generation for minimizing the global weighted coancestry. Strategies differed in the type of information used to compute global coancestries, the number and type of evaluated individuals, and the system of mating. Genealogical information proved to be very useful (at least for 10 generations of management) to arrange individuals' contributions via the minimization of global coancestry. In fact, the level of expected heterozygosity after 10 generations yielded by this strategy was 88–100% of the maximum possible improvement obtained if the genotype for all loci was known. Marker information was of very limited value if used alone. The amount and degree of polymorphism of markers to be used to compute molecular coancestry had to be high to mimic the performance of the strategy relying on pedigree, especially in the short term (for example, >10 markers per chromosome with 10 alleles each were needed if only the parents' genotype was available). When both sources of information are combined to calculate the coancestry conditional on markers, clear increases in effective population size (Ne) were found, but observed diversity levels (either gene or allelic diversity) in the early generations were quite similar to the ones obtained with pedigree alone. The advantage of including molecular information is greater when information is available on a greater number of individuals (offspring and parents vs. parents only). However, for realistic situations (i.e., large genomes) the benefits of using information on offspring are small. The same conclusions were reached when comparing the use of the different types of information (genealogical or/and molecular) to perform minimum coancestry matings.
Comparison of the X and Y Chromosome Organization in Silene latifolia
Authors: Zluvova Jitka , Janousek Bohuslav , Negrutiu Ioan , Vyskot Boris
Published: May 2005

Here we compare gene orders on the Silene latifolia sex chromosomes. On the basis of the deletion mapping results (11 markers and 23 independent Y chromosome deletion lines used), we conclude that a part of the Y chromosome (covering a region corresponding to at least 23.9 cM on the X chromosome) has been inverted. The gradient in silent-site divergence suggests that this inversion took place after the recombination arrest in this region. Because recombination arrest events followed by Y chromosome rearrangements also have been found in the human Y chromosome, this process seems to be a general evolutionary pathway.
Epistasis and the Adaptability of an RNA Virus
Authors: Sanjuán Rafael , Cuevas José M , Moya Andrés , Elena Santiago F
Published: May 2005

We have explored the patterns of fitness recovery in the vesicular stomatitis RNA virus. We show that, in our experimental setting, reversions to the wild-type genotype were rare and fitness recovery was at least partially driven by compensatory mutations. We compared compensatory adaptation for genotypes carrying (1) mutations with varying deleterious fitness effects, (2) one or two deleterious mutations, and (3) pairs of mutations showing differences in the strength and sign of epistasis. In all cases, we found that the rate of fitness recovery and the proportion of reversions were positively affected by population size. Additionally, we observed that mutations with large fitness effect were always compensated faster than mutations with small fitness effect. Similarly, compensatory evolution was faster for genotypes carrying a single deleterious mutation than for those carrying pairs of mutations. Finally, for genotypes carrying two deleterious mutations, we found evidence of a negative correlation between the epistastic effect and the rate of compensatory evolution.
Pericentromeric Regions of Soybean (Glycine max L. Merr.) Chromosomes Consist of Retroelements and Tandemly Repeated DNA and Are Structurally and Evolutionarily Labile
Authors: Lin Jer-Young , Jacobus Barbara Hass , SanMiguel Phillip , Walling Jason G , Yuan Yinan , Shoemaker Randy C , Young Nevin D , Jackson Scott A
Published: May 2005

Little is known about the physical makeup of heterochromatin in the soybean (Glycine max L. Merr.) genome. Using DNA sequencing and molecular cytogenetics, an initial analysis of the repetitive fraction of the soybean genome is presented. BAC 076J21, derived from linkage group L, has sequences conserved in the pericentromeric heterochromatin of all 20 chromosomes. FISH analysis of this BAC and three subclones on pachytene chromosomes revealed relatively strict partitioning of the heterochromatic and euchromatic regions. Sequence analysis showed that this BAC consists primarily of repetitive sequences such as a 102-bp tandem repeat with sequence identity to a previously characterized ∼120-bp repeat (STR120). Fragments of Calypso-like retroelements, a recently inserted SIRE1 element, and a SIRE1 solo LTR were present within this BAC. Some of these sequences are methylated and are not conserved outside of G. max and G. soja, a close relative of soybean, except for STR102, which hybridized to a restriction fragment from G. latifolia. These data present a picture of the repetitive fraction of the soybean genome that is highly concentrated in the pericentromeric regions, consisting of rapidly evolving tandem repeats with interspersed retroelements.
The Inactivation of KlNOT4, a Kluyveromyces lactis Gene Encoding a Component of the CCR4-NOT Complex, Reveals New Regulatory Functions
Authors: Mazzoni Cristina , Serafini Agnese , Falcone Claudio
Published: May 2005

We have isolated the KlNOT4 gene of the yeast Kluyveromyces lactis, which encodes a component of the evolutionarily conserved CCR4-NOT complex. We show that inactivation of the gene leads to pleiotropic defects that were differentially suppressed by the NOT4 gene of S. cerevisiae, indicating that these genes have overlapping, but not identical, functions. K. lactis strains lacking Not4p are defective in fermentation and show reduced transcription of glucose transporter and glycolytic genes, which are phenotypes that are not found in the corresponding mutant of S. cerevisiae. We also show that Not4 proteins control the respiratory pathway in both yeasts, although with some differences. They activate transcription of KlACS2 and KlCYC1, but repress KlICL1, ScICL1, ScACS1, and ScCYC1. Altogether, our results indicate that Not4p is a pivotal factor involved in the regulation of carbon metabolism in yeast.
Nonuniform radiation modeling of a corrugated plate photocatalytic reactor
Authors: Shang Huilan , Zhang Zisheng , Anderson William A.
Published: May 2005

Corrugated plate photocatalytic reactors provide a promising photoreactor design due to its potential in enhancing energy efficiency. A detailed model of such reactors is needed for engineering applications and process design. The model for the light absorption in a corrugated plate reactor using a nonuniform radiation source is developed based on first principles. The local area‐specific rate of energy absorption (LASREA) distribution on the corrugated plates is examined via simulation. The effect of the design parameters on LASREA is investigated. The results from this research provide feasible basis for design and optimization of corrugated plate photoreactors. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Structural and dynamic properties of cytochrome P450 BM‐3 in pure water and in a dimethylsulfoxide/water mixture
Authors: Roccatano Danilo , Wong Tuck Seng , Schwaneberg Ulrich , Zacharias Martin
Published: May 2005

Solvent molecules play an important role for the structural and dynamical properties of proteins. A major focus of current protein engineering is the development of enzymes that are catalytically active in the presence of organic solvents. The monooxygenase P450 BM‐3 is one of the best‐studied enzymes and promising for industrial applications but with limited activity in the presence of organic solvents or cosolvents. To gain insights into the structural and dynamical properties of the heme domain of this enzyme in solution, molecular dynamics simulations in pure water and in a 14% DMSO/water mixture were performed. The results of the simulations show overall similar structural fluctuations in both solvent systems, with no indication of partial or global unfolding. In 14% DMSO, the regions comprising the helices E, F, and the EF loop (implicated in controlling the entry to the active site channel) undergo a large shift. Significant changes were also observed near the active site access channel at the residue R47. During the simulation, no DMSO molecule penetrated the active site. However, a significant accumulation of DMSO molecules close to the substrate‐binding site and to the Flavin Mononucleotide (FMN) reductase domain interface was observed. © 2005 Wiley Periodicals, Inc. Biopolymers 78: 259–267, 2005
Randomized trial of traditional dissection with electrocautery versus ultrasonic fundus-first dissection in patients undergoing laparoscopic cholecystectomy
Authors: Cengiz Y , Jänes A , Grehn Å , Israelsson L A
Published: May 2005

Background

In laparoscopic cholecystectomy dissection can be with monopolar electrocautery or with ultrasonic shears, and can start at the triangle of Calot or at the fundus of the gallbladder.

Methods

Thirty-seven patients undergoing laparoscopic cholecystectomy were randomized to electrocautery dissection from the triangle of Calot and 43 to fundus-first dissection with ultrasonic shears. All procedures were strictly standardized, and patients and their postoperative carers were blinded to the operation performed.

Results

Ultrasonic fundus-first dissection was associated with a shorter duration of operation (mean 46 versus 61 min), fewer overnight hospital stays (two versus eight), lower pain scores 4 and 24 h after surgery, less nausea at 2, 4 and 24 h, and a shorter period of sick leave (mean 5·5 versus 9·3 days) compared with electrocautery from the triangle of Calot.

Conclusion

Ultrasonic fundus-first dissection during laparoscopic cholecystectomy was quicker and associated with less nausea and pain than electrocautery dissection from the triangle of Calot.
Simple Synthesis of Aminoquinoline/Ethylaniline Copolymer Semiconducting Nanoparticles
Authors: Li Xin‐Gui , Hua Yi‐Min , Huang Mei‐Rong
Published: May 2005

Pure copolymer nanoparticles from 8‐aminoquinoline (AQ) and 2‐ethylaniline (EA) were easily synthesized by a chemically oxidative polymerization in three different aqueous media. The potential and temperature of polymerization solution were used to successfully follow the polymerization progress. The molecular and morphological structures of the resulting AQ/EA copolymer particles were systematically characterized by IR, UV/Vis, NMR, gel permeation chromatography, laser particle‐size analysis, atomic force and transmission electron microscopy. The oxidation potential of the monomers as well as the polymerization yield, structure, and properties of the particles were found to significantly depend on AQ/EA ratio, polymerization temperature and medium. It is surprisingly found that AQ homopolymerization and AQ/EA (50:50) copolymerization at 5 °C in HCl simply afford nano‐ellipsoids with the major/minor axis diameters of 24/14 nm and 80/67 nm, respectively. A simple method of synthesizing semiconducting pure nanoparticles by introducing the AQ units with positively charged quaternary ammonium groups but in the absence of adscititious stabilizer or sulfonic substituent on the monomers is established first. Both the molecular weight and bulk electroconductivity of the copolymers exhibit a maximum at AQ content of 10 mol %. The solubility and film formability of the copolymers are good in highly polar solvents and reach the optimal at the AQ content of 20 and 10 mol %, respectively.
Enhanced chemotherapy delivery by intraarterial infusion and blood‐brain barrier disruption in malignant brain tumors
Authors: Fortin David , Desjardins Annick , Benko Andrew , Niyonsega Theophylle , Boudrias Marie
Published: May 2005

BACKGROUND

The treatment of malignant brain tumors is hampered by the presence of the blood‐brain barrier, which limits chemotherapy penetration to the central nervous system (CNS). In recent years, different strategies have been designed to circumvent this physiologic barrier. The osmotic blood‐brain barrier disruption (BBBD) procedure is one such strategy, and has been studied extensively in preclinical and clinical studies. The authors detail their experience so far with the procedure in the context of an open Phase II study in the treatment of malignant brain tumors.

METHODS

Patients with histologically proven malignant gliomas, primitive neuroectodermal tumors, primary CNS lymphomas, and metastatic disease to the brain were eligible. Patients enrolled were treated every 4 weeks (1 cycle) for ≤ 12 cycles. A methotrexate‐based regimen was offered to patients with lymphomas, whereas a carboplatin‐based regimen was offered to patients with all other histologies. Before intraarterial chemotherapy infusion, patients were submitted to an osmotic BBBD procedure.

RESULTS

Seventy‐two patients were included in the current report. The overall median survival times (MST) from treatment initiation for glioblastoma multiforme (GBM), anaplastic oligodendrogliomas, primary CNS lymphomas, and metastases were, respectively, 9.1, 13.9, not reached, and 9.9 months, whereas time to disease progression was 4.1, 9.2, 12.3, and 3.3 months. The MST from diagnosis was 32.2 months for GBM.

CONCLUSIONS

These encouraging results prompted the authors to further refine their knowledge of the potential contribution of this procedure in the treatment of brain tumors. These authors designed a randomized Phase III study for patients with GBM that is now open. Cancer 2005. © 2005 American Cancer Society.
Genetic interaction between Wnt7a and Lrp6 during patterning of dorsal and posterior structures of the mouse limb
Authors: Adamska Maja , Billi Allison C. , Cheek Susannah , Meisler Miriam H.
Published: May 2005

Wnt7a and the Wnt coreceptor Lrp6 are both required for development of posterior digits and dorsal structures of the limb. We report that Lrp6 null mice lack Lmx1b expression in the distal mesenchyme, as previously described for Wnt7a mutants. The loss of Lmx1b expression in Wnt7a−/−Lrp6+/− double mutants did not differ from that in Wnt7a−/− mice. These data suggest that Wnt7a acts through Lrp6 to regulate Lmx1b expression during dorsal specification. The loss of posterior skeletal elements in the Wnt7a−/−Lrp6+/− double mutant was much more severe than in Wnt7a−/− mice, suggesting that the Wnt7a−/− limb is protected by the action of other Lrp6 ligands. The data are consistent with the view that Wnt7a acts through Lrp6 and the canonical Wnt signaling pathway during dorsal and posterior limb development in the mouse. Developmental Dynamics 233:368–372, 2005. © 2005 Wiley‐Liss, Inc.
MultiPEGs: High Molecular Weight Multifunctional Poly(ethylene glycol)s Assembled by a Dendrimer‐Like Approach
Authors: Ballico Maurizio , Drioli Sara , Bonora Gian M.
Published: May 2005

New multifunctional, soluble and biocompatible polymeric systems exhibiting good physicochemical properties and good binding capacity have been obtained by assembly of smaller PEG components, selectively protected, purified and activated, by use of appropriate polyfunctional linkers. A general process for the synthesis of those derivatives was characterized by: a) selective derivatization of a PEG unit with a defined MW with an appropriate protecting group and activation of residual functional groups, and b) multiple condensation reactions of PEG units and linkers to provide multifunctional polyethylene glycol derivatives (MultiPEGs) of the desired size and complex structure. These complex‐structured MultiPEGs have larger numbers of functional groups, and probably better biodegradability, than commercial PEGs of comparable molecular weight. They can be advantageously used as carriers or stabilizers of pharmacologically or biologically active substances, and also as soluble supports for reagents and catalysts in liquid‐phase synthesis reactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Cobalt Bis(dicarbollides)(1–) Covalently Attached to the Calix[4]arene Platform: The First Combination of Organic Bowl‐Shaped Matrices and Inorganic Metallaborane Cluster Anions
Authors: Grüner Bohumír , Mikulášek Libor , Báča Jiří , Císařová Ivana , Böhmer Volker , Danila Crenguta , Reinoso‐García Marta M. , Verboom Willem , Reinhoudt David N. , Casnati Alessandro , Ungaro Rocco
Published: May 2005

Various calix[4]arene and resorc[4]arene ionic compounds substituted by cobalt bis(dicarbollide) anions (1) have been prepared for the first time. From tBu‐calix[4]arene (A) the complete series of mono‐, di‐, tri‐ and tetrasubstituted derivatives bearing one to four cluster anions on the lower rim (3–6) have been obtained in the form of their alkali‐metal salts by O‐alkylation with the 1‐dioxane derivative [8‐O(CH2CH2)2O(+)‐1,2‐C2B9H10)‐(1',2'‐C2B9H11)‐3,3'‐Co] (2), all of which are syn or cone isomers. In contrast, disubstitution of the dipropyl ether of tBu‐calix[4]arene (B) led to a mixture of the cone and 1,3‐alternate conformers 7a and 7b, respectively. Starting from tetrapropoxy‐calix[4]arene functionalised at the upper rim by carboxylic acid groups in distal positions (C) and an amino‐bridged derivative [8,8'‐μ‐H2N<(1,2‐C2B9H10)2‐3,3'‐Co] (8), calix[4]arene 9, disubstituted at the upper rim, was obtained as the main product along with the monosubstituted species 10. Di‐ and tetrasubstituted ionic products (11–15) were also obtained from resorcarene‐based cavitands by O‐alkylation with the 1‐dioxane derivative 2. A pair of regioisomeric disubstitution products, 11a,b, was isolated in the case of the hydroxy cavitand D, while E, functionalised by hydroxymethyl groups on the wide rim, and F, bearing hydroxy groups on the alkylidene bridges, gave the 1,3‐di‐ (12 and 14) and the tetrasubstituted compounds (13 and 15), respectively. The molecular structure of the electroneutral dicaesium complex of the dianion 4 was determined by single‐crystal X‐ray diffraction analysis. The two Cs+ cations are found in different coordination spheres in the structure of Cs24. Coordination of the Na+ cation by the diethylene glycol chain and one calixarene lower rim oxygen atom was found in the crystal structure of the Na complex of the monoanion 3. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Synthesis of Tricyclic Quinolones and Naphthyridones by Intramolecular Heck Cyclization of Functionalized Electron‐Rich Heterocycles
Authors: Beccalli Egle M. , Broggini Gianluigi , Martinelli Michela , Paladino Giuseppe , Zoni Caterina
Published: May 2005

Starting from commercially available pyrrole‐ and thiophene‐2‐carboxylic acids 1 or thiophene‐ and furan‐3‐carboxylic acids 6, we report the synthesis of tricyclic fused quinolone and naphthyridone derivatives, in only three steps, by an intramolecular Heck cyclization. We also report the use of microwave irradiation to obtain, in some cases, better yields of cyclized products. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
First Asymmetric Synthesis and Determination of the Absolute Configuration of a Lignan Isolated from Virola sebifera
Authors: Enders Dieter , Milovanovic Mile , Voloshina Elena , Raabe Gerhard , Fleischhauer Jörg
Published: May 2005

The first asymmetric synthesis of a lignan isolated from the seeds of Virola sebifera, one of the most widely spread Myristicaceae species in Brazil, in four steps (48 % overall yield) and with excellent stereoselectivity (de, ee ≥ 96 %) is described. The key step is the asymmetric Michael addition of a lithiated enantiopure α‐amino nitrile to an enone, followed by α‐methylation and cleavage of the amino nitrile. The absolute configuration of the naturally occurring 1,4‐diketone was determined by polarimetry as well as by CD spectroscopy and quantum chemical calculations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Converting Core Compounds into Building Blocks: The Concept of Regiochemically Exhaustive Functionalization
Authors: Marzi Elena , Bobbio Carla , Cottet Fabrice , Schlosser Manfred
Published: May 2005

In a model study, 3‐fluorophenol and 3‐fluoropyridine were converted into the each time four possible carboxylic acids by passing through the corresponding organometallic intermediates. As an attempt to generalize the findings reveals, a restricted set of principles and methods suffices to cope with all standard scenarios. The most valuable and versatile tools for the regiochemically exhaustive functionalization of a great variety of substrate patterns are the optionally site‐selective metalation (either by reagent/substrate matching or by peripheral coordination control), the use of activating or congesting protective groups and the basicity gradient‐driven heavy halogen migration (followed by halogen/metal permutation). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
First Asymmetric Synthesis of (+)‐Sordidin and (–)‐7‐epi‐Sordidin, Aggregation Pheromones of the Banana Weevil Cosmopolites sordidus
Authors: Enders Dieter , Breuer Irene , Nühring Anja
Published: May 2005

The asymmetric synthesis of (1S,3R,5R,7S)‐(+)‐sordidin and 7‐epi‐(1S,3R,5R,7R)‐(–)‐sordidin, both components of the natural male‐produced aggregation pheromone of the banana weevil Cosmopolites sordidus (Germar), starting from 2,2‐dimethyl‐1,3‐dioxan‐5‐one is described. Two of the stereogenic centers were generated by three α‐alkylations of the corresponding RAMP‐hydrazone. Diastereoselective epoxide opening as another key step of the synthesis employing the aza‐enolate of 3‐pentanone SAEP‐hydrazone as nucleophile and subsequent acidic intramolecular acetalisation furnished the sordidin C‐7 epimers in good overall yield (39 %) as a 1.5:1 diastereomeric mixture. The epimers could be separated by preparative GC and thus, each of them could be obtained in high diastereomeric and enantiomeric purity (de ≥ 97 %, ee ≥ 98 %). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Targeting gene expression in the mouse somite: Adenovirus‐mediated gene delivery and whole embryo culture
Authors: Chen Alice E. , Fan Chen‐Ming
Published: May 2005

We report here a novel approach to direct gene expression in the mouse somite based on the combined application of adenovirus‐mediated gene delivery and whole embryo ex vivo culture. As proof of principle, we show functional analysis of somites microinjected with an engineered virus expressing an activated form of Smoothened, the signaling receptor for Sonic Hedgehog (SHH). As adenovirus can infect many embryonic tissues in the mouse, this method may provide an effective alternative to conventional transgenesis for targeted spatial and temporal gene expression. genesis 42:71–76, 2005. © 2005 Wiley‐Liss, Inc.
Increased expression of ICAM‐3 is associated with radiation resistance in cervical cancer
Authors: Chung Young Min , Kim Byoung‐Gie , Park Chang‐Soo , Huh Seung Jae , Kim Jhingook , Park Jong Kuk , Cho Sun Mi , Kim Byung Soo , Kim Jun Suk , Yoo Young Do , Bae Duk‐Soo
Published: May 2005

To search for a marker that predicts the efficacy of radiation therapy in human cervical cancer, gene expression profiles between parental SiHa cervical cancer cells and radiation‐resistant SiHa/R cells have been compared by the microarray technique. Microarray and Northern blot analyses demonstrated that the ICAM‐3 expression was upregulated in SiHa/R cells. This increased expression of ICAM‐3 in SiHa cells enhanced cell survival by about 34.3% after a 2 Gy dosage of radiation. In addition, SiHa/ICAM‐3 cells showed a 2.45‐fold higher level of FAK phosphorylation than that of the control cells. In tumor specimens, ICAM‐3 staining was restricted to tumor stromal endothelial cells and lymphocytes. The overexpression of ICAM‐3 was significantly more frequent in radiation‐resistant cervical cancer specimens when compared with radiation‐sensitive specimens (83.3% vs. 35.3%; p = 0.015). With these observations, we can suggest that an increased expression of ICAM‐3 is associated with radiation resistance in cervical cancer cells and the expression of ICAM‐3 can be used as a valuable biomarker to predict the radiation resistance in cervical cancer that occurs during radiotherapy. © 2005 Wiley‐Liss, Inc.