bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simplified estimator of two and four gene relationship coefficients
Authors: THOMAS STUART C. 
Published: February 2010

AbstractMolecular marker data provide a means of circumventing the problem of not knowing the population structure of a natural population, as observed similarities between a pair’s genotypes provide information on their genetic relationship. Numerous method‐of‐moment (MOM) estimators have been developed for estimating relationship coefficients using this information. Here, I present a simplified form of Wang’s 2002 relationship estimator that is not dependent upon a previously required weighting scheme, thus improving the efficiency of the estimator when used with genuinely related pairs. The new estimator is compared against other estimators under a range of conditions, including situations where the parameter estimates are truncated to lie within the legitimate parameter space. The advantages of the new estimator are most notable for the two‐gene coefficient of relatedness. Truncating the MOM estimators results in parameter estimates whose properties are similar to maximum likelihood estimates, with them having generally lower sampling variances, but being biased.
Simultaneous spectroscopic and photometric observations of binary asteroids
Authors: Polishook D. , Brosch N. , Prialnik D. , Kaspi S. 
Published: February 2010

Abstract— We present results of visible wavelengths spectroscopic measurements (0.45 to 0.72 microns) of two binary asteroids, obtained with the 1‐m telescope at the Wise Observatory on January 2008. The asteroids 90 Antiope and 1509 Esclangona were observed to search for spectroscopic variations correlated with their rotation while presenting different regions of their surface to the viewer. Simultaneous photometric observations were performed with the Wise Observatory's 0.46 m telescope, to investigate the rotational phase behavior and possible eclipse events.90 Antiope displayed an eclipse event during our observations. We could not measure any slope change of the spectroscopic albedo within the error range of 3%, except for a steady decrease in the total light flux while the eclipse took place. We conclude that the surface compositions of the two components do not differ dramatically, implying a common origin and history.1509 Esclangona did not show an eclipse, but rather a unique lightcurve with three peaks and a wide and flat minimum, repeating with a period of 3.2524 hours. Careful measurements of the spectral albedo slopes reveal a color variation of 7 to 10 percent on the surface of 1509 Esclangona, which correlates with a specific region in the photometric lightcurve. This result suggests that the different features on the lightcurve are at least partially produced by color variations and could perhaps be explained by the existence of an exposed fresh surface on 1509 Esclangona.
Predictive and correlative techniques for the design, optimisation and manufacture of solid dosage forms
Authors: Hardy Ian J , Cook Walter G 
Published: February 2010

Abstract
There is much interest in predicting the properties of pharmaceutical dosage forms from the properties of the raw materials they contain. Achieving this with reasonable accuracy would aid the faster development and manufacture of dosage forms. A variety of approaches to prediction or correlation of properties are reviewed. These approaches have variable accuracy, with no single technique yet able to provide an accurate prediction of the overall properties of the dosage form. However, there have been some successes in predicting trends within a formulation series based on the physicochemical and mechanical properties of raw materials, predicting process scale-up through mechanical characterisation of materials and predicting product characteristics by process monitoring. Advances in information technology have increased predictive capability and accuracy by facilitating the analysis of complex multivariate data, mapping formulation characteristics and capturing past knowledge and experience.
Daily transdermal administration of selegiline to guinea-pigs preferentially inhibits monoamine oxidase activity in brain when compared with intestinal and hepatic tissues
Authors: Mawhinney Michael , Cole Dennis , Azzaro Albert J 
Published: February 2010

Abstract
Selegiline has been formulated in an acrylic polymer adhesive mixture to be employed as a constant release topical patch for daily transdermal administration. Application of this selegiline transdermal system (STS) to guinea-pigs resulted in an average delivery of 1.185 mg selegiline/cm2 patch/24 h. STS dose-response curves were generated by altering patch size (cm2). A transdermal dose range was identified which inhibited guinea-pig brain monoamine oxidase-B (MAO-B) by greater than 95 % yet provided for a dose-dependent inhibition of monoamine oxidase-A (MAO-A) activity. The ID50 for inhibition of MAO-A activity in response to a 21-day daily regimen with transdermal selegiline was approximately 7.5-fold lower for cortical and striatal brain regions compared with that obtained for duodenum; hepatic MAO-A was unaffected following the same dosing regimen. By contrast, orally administered selegiline inhibited brain and duodenal MAO-A to the same extent, and generated a shallower dose–inhibition curve for brain MAO-A inhibition. In addition, transdermal delivery was approximately 6–8-times more potent than oral selegiline for the inhibition of brain MAO-A activity. It is concluded that daily transdermal selegiline administration may provide therapeutic advantages over oral treatment, based on its preferential, dose-dependent inhibition of brain vs peripheral MAO-A activity.
Physical stability and enthalpy relaxation of drug-hydroxypropyl methylcellulose phthalate solvent change co-precipitates
Authors: Sertsou Gabriel , Butler James , Hempenstall John , Rades Thomas 
Published: February 2010

Abstract
The poorly water-soluble drug GWX was co-precipitated with hydroxypropyl methylcellulose phthalate (HPMCP) using a solvent change method. The two co-precipitate formulations made, with drug-HPMCP ratios of 2:8 and 5:5, were analysed using modulated temperature differential scanning calorimetry. They were found to consist of completely amorphous solid solution and a mixture of amorphous solid solution, crystalline drug and amorphous drug, respectively. Stability with respect to crystallization of the two co-precipitates and pure amorphous drug made by quench cooling was compared by storing preparations at 25°C and 40°C, under vacuum over P2O5, and at 75% relative humidity (r.h.). Humidity (75% r.h. compared with dry) had a larger influence on crystallization of the amorphous drug than temperature (25°C compared with 40°C). The solid solution phase in co-precipitates had a relatively higher stability than amorphous drug alone, with respect to crystallization, in presence of the plasticizer water, and crystalline drug. These findings were partly explained by evidence of decreased molecular mobility in the amorphous solid solution with respect to amorphous drug alone, using enthalpy relaxation measurements. At an ageing temperature of 65°C, the calculated half-life for enthalpy relaxation of the 2:8 drug–HPMCP ratio coprecipitate was about 6 orders of magnitude greater than that of amorphous drug alone, indicating a large difference in relative molecular mobility.
Influence of route of administration on the absorption and disposition of α,- γ- and δ-tocotrienols in rats
Authors: Yap Siew Ping , Yuen Kah Hay , Lim Ai Beoy 
Published: February 2010

AbstractA study was conducted to evaluate the bioavailability of α-, γ- and δ-tocotrienols administered via oral, intravenous, intramuscular and intraperitoneal routes in rats. Three separate experiments, each conducted according to a two-way crossover design, were carried out to compare intravenous and oral, intramuscular and oral, and intraperitoneal and oral administration. Oral absorption of all three tocotrienols was found to be incomplete. Of the three tocotrienols, α-tocotrienol had the highest oral bioavailability, at about 27.7 ± 9.2%, compared with γ- and δ-tocotrienols, which had values of 9.1 ± 2.4% and 8.5 ± 3.5%, respectively. Such biodiscrimination was also observed in their total clearance rates (estimated from the intravenous data). α-Tocotrienol showed the lowest clearance rate at about 0.16 L kg−1 h−1, whereas that of δ- and γ-tocotrienols was quite similar, with values of 0.24 and 0.23 L kg−1 h−1, respectively. Interestingly, all three tocotrienols were found to be negligibly absorbed when administered intraperitoneally and intramuscularly. Thus, these two routes of administration should be avoided when evaluating the biological activities of the tocotrienols in whole animal experiments.
Age-related alteration of haloperidol–serum protein binding
Authors: Koyama Hikaru , Mori Satoru , Sugioka Nobuyuki , Nishihara Takehiro , Nakajima Kenji 
Published: February 2010

AbstractSerum haloperidol levels were determined in 59 patients, 50–88 years old, with psychosis, receiving long-term treatment with haloperidol. Although the total (bound and free form) haloperidol level in serum showed a linear correlation with daily dose, there was a larger variation in the relationship between free form and the daily dose compared with total because of inter-individual variation in the serum protein binding of haloperidol. The free fraction of haloperidol in serum increased with age. There was no difference in the ratio of total haloperidol level per daily dose between the adult and elderly groups, whereas the ratio of free haloperidol level per daily dose was significantly higher in the elderly than in the adult group. In the elderly, therefore, the therapeutic window of haloperidol should be assessed using free form level ratherthan total level, which is influenced by serum protein binding of the drug.
Involvement of nuclear factor-κB in lipoteichoic acid-induced cyclooxygenase-2 expression in RAW 264.7 macrophages
Authors: Chiang L L , Kuo C T , Wang C H , Chen T F , Ho Y S , Kuo H P , Lin C H 
Published: February 2010

AbstractWe have investigated the role of protein kinase C (PKC) and nuclear factor-κB (NF-κB) in cyclooxygenase-2 (COX-2) expression caused by Staphylococcus aureus lipoteichoic acid in RAW 264.7 macrophages. A phosphatidylcholine-phospholipase C (PC-PLQ inhibitor (D-609) and a phosphatidyl-inositol-phospholipase C (Pl-PLC) inhibitor (U-73122) attenuated lipoteichoic acid-induced COX-2 expression, while a phosphatidate phosphohydrolase inhibitor (propranolol) had no effect. Two PKC inhibitors (Go 6976 and Ro 31–8220) and the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), also attenuated lipoteichoic acid-induced COX-2 expression. Lipoteichoic acid resulted in a decrease in PKC activity in the cytosol and an increase in PKC activity in membranes. The lipoteichoic acid-induced translocation of p65 NF-κB from the cytosol to the nucleus was inhibited by D-609, U-73122, Go 6976, Ro 31–8220, and PDTC., but not by propranolol. The results suggested that lipoteichoic acid might have activated PC-PLC and Pl-PLC to induce PKC activation, which in turn initiated NF-κB activation, and finally induced COX-2 expression in RAW 264.7 macrophages.
Assessment and prevention of gastrointestinal toxicity of non-steroidal anti-inflammatory drugs
Authors: Lane Majella E , Kim Mi-Jeong 
Published: February 2010

AbstractNon-steroidal anti-inflammatory drugs (NSAIDs) are widely used for analgesic, anti-inflammatory and, in the case of aspirin, for anti-thrombotic actions. The serious gastrointestinal side-effects associated with these drugs are of concern and pose a significant obstacle to their use. This review discusses the pathogenic mechanisms by which the conventional acidic NSAIDs induce gastrointestinal toxicity, with particular emphasis on non-prostaglandin effects. Methods of assessment of NSAID-induced enteropathy are reviewed, with particular emphasis on the use of functional measurement of NSAID-induced changes in the gastrointestinal tract. The advances in our knowledge of the pathogenesis of these effects have resulted in the development of a range of novel NSAIDs. Where functional assessment of the effects of NSAIDs has been employed, it appears to be more useful as an indicator of early-stage changes rather than a predictor of the effects of long-term NSAID exposure. Successful pharmaceutical strategies now offer considerable promise for reducing the severity of NSAID damage to the gastrointestinal tract. The utility of intestinal permeability measurements for selection and assessment of these strategies is discussed.
South Beauty Group: In Quest of a 'Beautiful' Growth Story
Authors: Xu Leiping , Velamuri S. Ramakrishna 
Published: February 2010

Since the 1990s, China's catering industry had boomed sharply with over 15% CAGR (Compound Annual Growth Rate). In 2007, the catering market size of RMB1,200 billion (US$155 billion) accounted for 4.87% of GDP (Gross Domestic Product) in China. This percentage was only 1.5% in 1978. China's restaurant market was in a typical state of perfect competition, not only in terms of the number of players, but also in terms of the food varieties. Intrigued by the successful story of western fast food in China, the leading Chinese players were exploring how to expand their scale through the development of restaurant chains. Considering the difficulties of standardizing Chinese cuisine, the scale expansion of the Chinese Dinner segment was slower than that of Hot Pot and Chinese fast food segments. It was October 18th, 2007. As an innovative upper-middle player in the Chinese Dinner segment, the South Beauty Group, with 20 restaurants and two soon-to-be-opened restaurants under three different brands, was dreaming about expanding its scale to 100 restaurants in three years (35 in China and 65 in the international market). To meet this ambitious target, the Group faced many challenges, including standardizing Chinese cuisine, selection of domestic and international locations, development of franchising operations and the launch of an IPO. Moreover, as the only Food Service Partner of Chinese cuisine for the 2008 Beijing Olympics, the Group also had to organize the company's resources efficiently to fulfill this prestigious contract. This case had been developed mainly for MBA and EMBA students, with the main teaching objective being to understand the challenges of growth. The students will also be exposed to the dynamic Chinese business environment and the dreams, innovativeness and decision-making behaviors of Chinese entrepreneurs, even in such a traditional industry. An audio-visual support, including an introduction to the company, the restaurants and the dishes, and two interviews with Ms. Zhang Lan is available to instructors.
Extreme Summer Convection in South America
Authors: Romatschke Ulrike , Houze Robert A. 
Published: February 2010

AbstractTropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) and National Centers for Environmental Prediction–National Center for Atmospheric Research (NCEP–NCAR) reanalysis data are used to indicate mechanisms responsible for extreme summer convection over South America. The three-dimensional reflectivity field is analyzed to define three types of extreme echo, deep convective cores, wide convective cores, and broad stratiform regions. The location and timing of these echoes are sensitive to midlatitude synoptic disturbances crossing the Andes. At the leading edges of these disturbances the nocturnal South American low-level jet (SALLJ) transports moisture along the eastern edge of the Andes from the tropical to the subtropical part of the continent. Where the SALLJ rises over lower but steep mountains on the east side of the southern central Andes, deep and wide convective cores are triggered in the evening. When the SALLJ withdraws to the north as the disturbance passes, nocturnal triggering occurs in the northeastern foothills of the central Andes. Extreme convection over the Amazon basin takes the form of broad stratiform regions that evolve from systems with wide convective cores moving into the center of the region from both the southwest and northeast. The systems from the northeast form at the northeast coast and are likely squall lines. Along the coast of the Brazilian Highlands, diurnal/topographic forcing leads to daytime maxima of deep convective cores followed a few hours later by wide convective cores. Wide convective cores and broad stratiform regions form in the South Atlantic convergence zone (SACZ) with a diurnal cycle related to continental heating.
Impacts of Polarimetric Radar Observations on Hydrologic Simulation
Authors: Gourley Jonathan J. , Giangrande Scott E. , Hong Yang , Flamig Zachary L. , Schuur Terry , Vrugt Jasper A. 
Published: February 2010

Abstract
Rainfall estimated from the polarimetric prototype of the Weather Surveillance Radar-1988 Doppler [WSR-88D (KOUN)] was evaluated using a dense Micronet rain gauge network for nine events on the Ft. Cobb research watershed in Oklahoma. The operation of KOUN and its upgrade to dual polarization was completed by the National Severe Storms Laboratory. Storm events included an extreme rainfall case from Tropical Storm Erin that had a 100-yr return interval. Comparisons with collocated Micronet rain gauge measurements indicated all six rainfall algorithms that used polarimetric observations had lower root-mean-squared errors and higher Pearson correlation coefficients than the conventional algorithm that used reflectivity factor alone when considering all events combined. The reflectivity based relation R(Z) was the least biased with an event-combined normalized bias of −9%. The bias for R(Z), however, was found to vary significantly from case to case and as a function of rainfall intensity. This variability was attributed to different drop size distributions (DSDs) and the presence of hail. The synthetic polarimetric algorithm R(syn) had a large normalized bias of −31%, but this bias was found to be stationary.
To evaluate whether polarimetric radar observations improve discharge simulation, recent advances in Markov Chain Monte Carlo simulation using the Hydrology Laboratory Research Distributed Hydrologic Model (HL-RDHM) were used. This Bayesian approach infers the posterior probability density function of model parameters and output predictions, which allows us to quantify HL-RDHM uncertainty. Hydrologic simulations were compared to observed streamflow and also to simulations forced by rain gauge inputs. The hydrologic evaluation indicated that all polarimetric rainfall estimators outperformed the conventional R(Z) algorithm, but only after their long-term biases were identified and corrected.
Separation of graft-versus-host disease from graft-versus-leukemia responses by targeting CC-chemokine receptor 7 on donor T cells
Authors: Coghill James M. , Carlson Michael J. , Panoskaltsis-Mortari Angela , West Michelle L. , Burgents Joseph E. , Blazar Bruce R. , Serody Jonathan S. 
Published: February 2010

AbstractCC-chemokine receptor 7 (CCR7) is expressed on the surface of naive T cells, and plays a critical role in their movement into secondary lymphoid tissue. Here, we show that murine T cells lacking CCR7 (CCR7−/−) generate attenuated graft-versus-host disease (GVHD) responses compared with wild-type (WT) cells, with the difference varying inversely with the degree of major histocompatibility complex (MHC) disparity between the donor and recipient. CCR7−/− T cells exhibited an impaired ability to traffic to recipient lymph nodes, with an increased capacity to home to the spleen. CCR7−/− T cells, however, demonstrated a reduced ability to undergo in vivo expansion in the spleen due to impaired interactions with splenic antigen-presenting cells. On a cellular level, CCR7−/− T cells were functionally competent, demonstrating a normal in vitro proliferative capacity and a preserved ability to produce inflammatory cytokines. Importantly, CCR7−/− T cells were capable of generating robust graft-versus-leukemia (GVL) responses in vivo, as well as complete donor T-cell reconstitution. CCR7−/− regulatory T cells were able to protect against lethal GVHD when administered before WT conventional T cells. Our data suggest that CCR7 inhibition in the early posttransplantation period may represent a feasible new therapeutic approach for acute GVHD attenuation without compromising GVL responses.
STAT3 controls the neutrophil migratory response to CXCR2 ligands by direct activation of G-CSF–induced CXCR2 expression and via modulation of CXCR2 signal transduction
Authors: Nguyen-Jackson Hoainam , Panopoulos Athanasia D. , Zhang Huiyuan , Li Haiyan S. , Watowich Stephanie S. 
Published: February 2010

AbstractNeutrophil mobilization, the release of neutrophils from the bone marrow reserve into circulating blood, is important to increase peripheral neutrophil amounts during bacterial infections. Granulocyte colony-stimulating factor (G-CSF) and chemokines, such as macrophage-inflammatory protein-2 (MIP-2; CXCL2), can induce neutrophil mobilization, but the mechanism(s) they use remain unclear. Signal transducers and activator of transcription 3 (STAT3) is the principal intracellular signaling molecule activated upon G-CSF ligation of its receptor. Using a murine model with conditional STAT3 deletion in bone marrow, we demonstrated previously that STAT3 regulates acute G-CSF–responsive neutrophil mobilization and MIP-2–dependent neutrophil chemotaxis. In this study, we show STAT3 is also necessary for MIP-2–elicited neutrophil mobilization. STAT3 appears to function by controlling extracellular signal-regulated kinase (ERK) activation, which is important for MIP-2–mediated chemotaxis. In addition, we demonstrate that G-CSF stimulates the expression of the MIP-2 receptor via STAT3-dependent transcriptional activation of Il8rb. G-CSF treatment also induces STAT3-dependent changes in bone marrow chemokine expression levels which may further affect neutrophil retention and release. Taken together, our study demonstrates that STAT3 regulates multiple aspects of chemokine and chemokine receptor expression and function within the bone marrow, indicating a central role in the neutrophil mobilization response.
A zinc-finger transcriptional activator designed to interact with the γ-globin gene promoters enhances fetal hemoglobin production in primary human adult erythroblasts
Authors: Wilber Andrew , Tschulena Ulrich , Hargrove Phillip W. , Kim Yoon-Sang , Persons Derek A. , Barbas Carlos F. , Nienhuis Arthur W. 
Published: February 2010

Abstract
Fetal hemoglobin (HbF) is a potent genetic modifier of the severity of β-thalassemia and sickle cell anemia. We used an in vitro culture model of human erythropoiesis in which late-stage erythroblasts are derived directly from human CD34+ hematopoietic cells to evaluate HbF production. This system recapitulates expression of globin genes according to the developmental stage of the originating cell source. When cytokine-mobilized peripheral blood CD34+ cells from adults were cultured, background levels of HbF were 2% or less. Cultured cells were readily transduced with lentiviral vectors when exposed to vector particles between 48 and 72 hours. Among the genetic elements that may enhance fetal hemoglobin production is an artificial zinc-finger transcription factor, GG1-VP64, designed to interact with the proximal γ-globin gene promoters. Our data show that lentiviral-mediated, enforced expression of GG1-VP64 under the control of relatively weak erythroid-specific promoters induced significant amounts of HbF (up to 20%) in erythroblasts derived from adult CD34+ cells without altering their capacity for erythroid maturation and only modestly reducing the total numbers of cells that accumulate in culture after transduction. These observations demonstrate the potential for sequence-specific enhancement of HbF in patients with β-thalassemia or sickle cell anemia.