bluuebunny/crossref_metadata_2025_split huggingface dataset:
Directed evolution strategies for improved enzymatic performance
Authors: Hibbert Edward G , Dalby Paul A 
Published: October 2005

Abstract
The engineering of enzymes with altered activity, specificity and stability, using directed evolution techniques that mimic evolution on a laboratory timescale, is now well established. However, the general acceptance of these methods as a route to new biocatalysts for organic synthesis requires further improvement of the methods for both ease-of-use and also for obtaining more significant changes in enzyme properties than is currently possible. Recent advances in library design, and methods of random mutagenesis, combined with new screening and selection tools, continue to push forward the potential of directed evolution. For example, protein engineers are now beginning to apply the vast body of knowledge and understanding of protein structure and function, to the design of focussed directed evolution libraries, with striking results compared to the previously favoured random mutagenesis and recombination of entire genes. Significant progress in computational design techniques which mimic the experimental process of library screening is also now enabling searches of much greater regions of sequence-space for those catalytic reactions that are broadly understood and, therefore, possible to model.
Biocatalysis for organic synthesis frequently makes use of whole-cells, in addition to isolated enzymes, either for a single reaction or for transformations via entire metabolic pathways. As many new whole-cell biocatalysts are being developed by metabolic engineering, the potential of directed evolution to improve these initial designs is also beginning to be realised.
Patients' perspectives on how idiopathic pulmonary fibrosis affects the quality of their lives
Authors: Swigris Jeffrey J , Stewart Anita L , Gould Michael K , Wilson Sandra R 
Published: October 2005

Abstract

Background
Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease with a survival of only three to five years from the time of diagnosis. Due to a paucity of studies, large gaps remain in our understanding of how IPF affects the quality of patients' lives. In only one other study did investigators ask patients directly for their perspectives on this topic. Further, currently there is no disease-specific instrument to measure health-related quality of life (HRQL) in patients with IPF. A carefully constructed measurement instrument, sensitive to underlying change, is needed for use in clinical trials and longitudinal studies of patients with IPF. Before developing such an instrument, researchers must improve their understanding of the relevant effects of IPF on patients' lives. On a broader scale, to provide the best care for people with IPF, clinicians must appreciate – from patients' perspectives – how this disease affects various aspects of their lives.

Methods
We used focus groups and individual in-depth interviews with 20 IPF patients to collect their perspectives on how IPF affects their lives (with a focus on the quality of their lives). We then analyzed these perspectives and organized them into a conceptual framework for describing HRQL in patients with IPF. Next, we examined how well certain existing measurement instruments – which have been administered to IPF patients in prior studies – covered the domains and topics our patients identified.

Results
In our framework, we identified 12 primary domains: symptoms, IPF therapy, sleep, exhaustion, forethought, employment and finances, dependence, family, sexual relations, social participation, mental and spiritual well-being, mortality. Each domain is composed of several topics, which describe how IPF affects patients' lives. When we compared the content of our conceptual framework with the existing instruments, we found the coverage of the existing instruments to be inadequate for several reasons, including they may tap general areas of QOL or HRQL but not some areas that appear to be most directly affected by IPF, and they include items that are relevant to symptoms and effects of other respiratory diseases but not IPF.

Conclusion
Collecting patients' perspectives and developing an organized inventory of the relevant effects of IPF on patients' lives provides valuable information for improving our understanding of the impact of this disease on patients and their loved ones. We believe our findings will help alert clinicians and researchers to IPF patients' experiences and concerns. Based on the comparison or our conceptual framework with the content of four existing instruments, it would appear that developing an IPF-specific measurement instrument is justified. Our conceptual framework for describing health-related quality of life in patients with IPF lays a solid foundation for constructing such an instrument.
Retroperitoneal inflammatory myofibroblastic tumor
Authors: Attili Suresh VS , Chandra C Rama , Hemant Dadhich K , Bapsy Poonamalle P , RamaRao Clementeena , Anupama G 
Published: October 2005

Abstract

Background
Inflammatory myofibroblastic tumor (IMT) is a neoplasm of unknown etiology occurring at various sites. By definition, it is composed of spindle cells (myofibroblasts) with variable inflammatory component, hence the name is IMT.

Case presentation
The present case is of a 46 years old woman presented with a history of flank pain, abdominal mass and intermittent hematuria for last 6 months. The initial diagnosis was kept as renal cell carcinoma. Finally, it turned out to be a case of retroperitoneal IMT. The patient was managed by complete surgical resection of the tumor.

Conclusion
IMT is a rare neoplasm of uncertain biological potential. Complete surgical resection remains the mainstay of the treatment.
Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice
Authors: Heneka Michael T , Sastre Magdalena , Dumitrescu-Ozimek Lucia , Dewachter Ilse , Walter Jochen , Klockgether Thomas , Van Leuven Fred 
Published: October 2005

Abstract

Background
Inflammation is suspected to contribute to the progression and severity of neurodegeneration in Alzheimer's disease (AD). Transgenic mice overexpressing the london mutant of amyloid precursor protein, APP [V717I], robustly recapitulate the amyloid pathology of AD.

Methods
Early and late, temporal and spatial characteristics of inflammation were studied in APP [V717I] mice at 3 and 16 month of age. Glial activation and expression of inflammatory markers were determined by immunohistochemistry and RT-PCR. Amyloid deposition was assessed by immunohistochemistry, thioflavine S staining and western blot experiments. BACE1 activity was detected in brain lysates and in situ using the BACE1 activity kit from R&D Systems, Wiesbaden, Germany.

Results
Foci of activated micro- and astroglia were already detected at age 3 months, before any amyloid deposition. Inflammation parameters comprised increased mRNA levels coding for interleukin-1β, interleukin-6, major histocompatibility complex II and macrophage-colony-stimulating-factor-receptor. Foci of CD11b-positive microglia expressed these cytokines and were neighbored by activated astrocytes. Remarkably, β-secretase (BACE1) mRNA, neuronal BACE1 protein at sites of focal inflammation and total BACE1 enzyme activity were increased in 3 month old APP transgenic mice, relative to age-matched non-transgenic mice. In aged APP transgenic mice, the mRNA of all inflammatory markers analysed was increased, accompanied by astroglial iNOS expression and NO-dependent peroxynitrite release, and with glial activation near almost all diffuse and senile Aβ deposits.

Conclusion
The early and focal glial activation, in conjunction with upregulated BACE1 mRNA, protein and activity in the presence of its substrate APP, is proposed to represent the earliest sites of amyloid deposition, likely evolving into amyloid plaques.
Branching projections of ventrolateral reticular neurons to the medial preoptic area and lumbo-sacral spinal cord
Authors: Russo Antonella , Pellitteri Rosalia , Romeo Rosa , Stanzani Stefania , Jean André 
Published: October 2005

Abstract
Different findings indicate that rostral ventrolateral reticular nucleus (RVL) is neuronal substrate of integration and regulation of the cardiovascular functions. Some efferent RVL neurons project to the thoraco-lumbar spinal cord and excite preganglionic sympathetic neurons, to the spinal phrenic motor neurons involved in inspiratory function and increase the activity of vasoconstrictor fibres innervating blood vessels in the skin and skeletal muscle. Our study was aimed at revealing presence of neurons within RVL supplying branching collateral input to the medial preoptic area (MPA) and to the lumbo-sacral spinal cord (SC-L) in the rat. All animal experiments were carried out in accordance with current institutional guidelines for the care and use of experimental animals. We have employed double fluorescent-labelling procedure: the projections were defined by injections of two retrograde tracers: Rhodamine Labelled Bead (RBL) and Fluoro Gold (FG) in the MPA and SC-L, respectively. Our results showed the presence of few single FG neurons and single RBL neurons in the RVL. The size of FG-neurons and RBL-neurons was medium (25–30 μm) and large (50 μm).
Few double-projecting neurons were distributed in the middle third of RVL nucleus, their size was 30–40 μm. The results demonstrate that pools of neurons in the RVL have collateral projections to the MPA and SC-L and they are involved in ascending and descending pathway. These data suggest that these neurons could play a role in maintaining activity of central and peripheral blood flow.
25-Hydroxyvitamin D31α-hydroxylase expression in breast cancer and use of non-1α-hydroxylated vitamin D analogue
Authors: Segersten Ulrika , Holm Pernille Kaae , Björklund Peyman , Hessman Ola , Nordgren Hans , Binderup Lise , Åkerström Göran , Hellman Per , Westin Gunnar 
Published: October 2005

Abstract
Introduction
The cytochrome P450 mitochondrial enzyme 25-hydroxyvitamin D3 1α-hydroxylase (1α-hydroxylase) of renal tubule cells hydroxylates the major circulating form of vitamin D (25(OH)D3) to the active systemic hormone 1,25(OH)2D3. Local production of 1,25(OH)2D3 appears to occur also at other sites where 1α-hydroxylase is expressed for autocrine/paracrine regulation. To reduce risks of hypercalcemia during treatment with vitamin D, we have previously suggested use of non-1α-hydroxylated vitamin D analogues to target tissues where 1α-hydroxylase is expressed, including the parathyroid glands in secondary hyperparathyroidism. The present study was undertaken to examine expression of 1α-hydroxylase in breast cancer and to investigate whether a non-1α-hydroxylated vitamin D analogue displayed biological function. In addition, expression of the 25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase) and the vitamin D receptor (VDR) was investigated.

Methods
The expression of 1α-hydroxylase, 24-hydroxylase and VDR was investigated in breast cancer specimens (n = 19) and normal breast tissues (n = 10) by immunohistochemistry and/or RT-PCR. Consecutive cryosections of 6 μm essentially free of immune cells were used in the analyses. The effect of vitamin D analogues on transcriptional activation was analyzed in transiently transfected MCF-7 breast cancer cells.

Results
1α-hydroxylase protein was demonstrated in 79% and 100% of breast cancer specimens and normal breast, respectively. The overall relative mRNA levels of 1α-hydroxylase and 24-hydroxylase in normal breast compared to breast tumors were: 1α-hydroxylase, 1 ± 0.07 versus 0.7 ± 0.05, respectively (p < 0.001); 24-hydroxylase, 1 ± 0.08 verus 2.1 ± 0.2, respectively (p < 0.001). The VDR was expressed in 95% of the tumors as expected, with mRNA levels of 1 ± 0.09 and 1.4 ± 0.12 (p < 0.05) in breast cancer and normal breast, respectively. The ketoconazole-sensitive transcription activation potential of the non-1α-hydroxylated vitamin D analogue prodrug of EB1089 (EB1285) was demonstrated in MCF-7 cells, which express 1α-hydroxylase. The activity of EB1285 was about 20% of 1,25(OH)2D3.

Conclusion
These results demonstrate nearly normal expression levels of 1α-hydroxylase, 24-hydroxylase and VDR in the majority of investigated breast cancer specimens. A non-1α-hydroxylated vitamin D analogue displayed activity in breast cancer cells. Such analogues may present future therapeutic options for proliferative disorders where 1α-hydroxylase is expressed.
Respiratory syncytial virus infections: characteristics and treatment
Authors: Chidgey Sharon M , Broadley Kenneth J 
Published: October 2005

Abstract
In this review, we describe the history, epidemiology and clinical manifestations of infections attributed to respiratory syncytial virus (RSV) in children. At present, no cure exists for RSV infection but commonly employed palliative treatments include oxygen and inhaled β2-adrenoceptor agonists, such as salbutamol, to relieve the wheezing and increased bronchiolar smooth muscle constriction. Adrenaline (epinephrine) has been found to be superior to the selective β2-adrenoceptor agonists. Oral or inhaled corticosteroids should counteract the inflammatory response to RSV infection but their effectiveness is controversial. Inhaled ribavirin is the only licensed antiviral product approved for the treatment of RSV lower respiratory-tract infection in hospitalized children, although its use is now restricted to high-risk infants. Other treatments considered are nasopharyngeal suctioning, surfactant therapy, recombinant human deoxyribonuclease I, heliox (helium:oxygen) and inhaled nitric oxide. Prevention of infection by RSV antibodies is another strategy and, currently, palivizumab is the only safe, effective and convenient preventative treatment for RSV disease in high-risk populations of infants and young children. Its cost-effectiveness, however, has been questioned. Both live attenuated and subunit vaccines against RSV infection have been developed but so far there is no safe and effective vaccine available. Finding effective treatments and prophylactic measures remains a major challenge for the future.
Esterification of Long Chain Aliphatic Acids with Long Chain Alcohols Catalyzed by Multi-valent Metal Salts
Authors: Mantri Kshudiram , Nakamura Ryo , Komura Kenichi , Sugi Yoshihiro 
Published: October 2005

Abstract
Some typical multi-valent metal salts, such as chloride, nitrate, sulfate, and acetate of Fe(III), Al(III), Ga(III), In(III), Zr(IV), Hf(IV), Zn(II), Co(II), Ni(II), Mn(III), Cr(III), and Cu(II) have catalytic acitivties for the esterification of saturated and unsaturated long chain aliphatic acids with long chain aliphatic alcohols. These catalysts were sponteneously separated from the reaction mixtures, and could be subjected to the recycle use for the further reactions.
Lewis Base-catalyzed Cyanomethylation of Carbonyl Compounds with (Trimethylsilyl)acetonitrile
Authors: Kawano Yoshikazu , Kaneko Nobuya , Mukaiyama Teruaki 
Published: October 2005

Abstract
Catalytic cyanomethylation of various carbonyl compounds with (trimethylsilyl)acetonitrile (TMSCH2CN) in the presence of Lewis bases such as cesium or lithium acetate proceeded smoothly to afford the corresponding cyanomethylated adducts in good yields.
Preparation and Electrochemical Characterization of Ferrocenyl-coated Polystyrene Monodispersed Latex Particle
Authors: Han Limin , Chen Jingyuan , Ikeda Isao 
Published: October 2005

Abstract
The mono dispersed redox-active latex particle with 0.90 μm in diameter was prepared by immobilizing ferrocenylmethanol acrylate on a surface of a polystyrene latex core through the emulsion copolymerization reaction. The aqueous suspensions exhibited stable voltammetric waves at 0.271/0.207 V vs Ag|AgCl. The anodic and the cathodic peak currents were diffusion-controlled, as if it were huge redox molecules with 3.8 × 107 electrons.
The Sonochemiluminescence of Lucigenin in N,N-Dimethylformamide Solution under the Influence of Natural Flavonoids
Authors: Wang Jian , Huang Liyan , Chen Guonan , Huang Jinling 
Published: October 2005

Abstract
The sonochemiluminescence (SCL) of lucigenin in N,N-dimethylformamide was investigated. It is found that flavonoids can effectively inhibit this type of SCL and the inhibition of flavonoids parallel very well to their radical-scavenging capacity. These results provide useful data for establishing methods to assess the radical.
Dispersion Behavior and Spectroscopic Properties of Single-walled Carbon Nanotubes in Chitosan Acidic Aqueous Solutions
Authors: Takahashi Teruo , Luculescu Catalin Romeo , Uchida Katsumi , Ishii Tadahiro , Yajima Hirofumi 
Published: October 2005

Abstract
We found that the cationic polysaccharide chitosan is an efficient dispersion agent for single-walled carbon nanotubes (SWNTs). The spectroscopic properties of chitosan–SWNTs dispersion are different from sodium dodecyl sulfate (SDS)–SWNTs dispersion in acidic conditions. It has been revealed that chitosan is efficiently protective against the protonation of SWNTs. The dispersion behavior of SWNTs in chitosan solutions will be discussed.
Structure and Magnetic Properties of a Low-spin Manganese(III) Phthalocyanine Dicyanide Complex
Authors: Matsuda Masaki , Yamaura Jun-Ichi , Tajima Hiroyuki , Inabe Tamotsu 
Published: October 2005

Abstract
A manganese(III) complex salt, TPP[MnIII(Pc)(CN)2]·DCM was crystallized in dichloromethane solution (Pc = phthalocyaninato, TPP+ = tetraphenylphosphonium, and DCM = dichloromethane). In the crystal, Pc molecules form a pair of one-dimensional regular chains along the c axis. The magnetic susceptibility measurement revealed Mn ions in the low-spin state (S = 1) and a spin–orbit coupling effect due to the incomplete quenching of the angular orbital moment under the symmetrical ligand field.
Reviews of the 2005 Economic Report of the President
Authors: Farrell Joseph , Gruber Jonathan , Hall Robert E , Hanson Gordon H , Slemrod Joel 
Published: October 2005

The Journal of Economic Literature (JEL) regularly reviews books of interest to the economics profession. The Economic Report of the President (ERP) falls under that purview and beginning this year, the JEL will be reviewing the ERP. Toward that end, I have asked a handful of very prominent economists to review the 2005 ERP. Reviewers were chosen to reflect expertise on what I guessed would be key issues. Reviewers were given the following instructions: The ERP in principle should provide an accurate assessment of the consensus professional views of economists on any given issue, based on the research to date. Does the discussion in the ERP in fact accurately summarize what we as economists know? Reviewers were given free rein over what material they would review in the ERP but were urged to focus on their areas of particular expertise. In the reviews that follow, Joel Slemrod reviews the discussion of tax reform. Joe Farrell reviews the ERP's chapter titled “Innovation and the Information Economy.” Gordon Hanson reviews the chapters on international trade and on immigration. Robert Hall reviews the discussion of the adverse macroeconomic impact of rising oil prices while Jonathan Gruber reviews the ERP chapter titled “Expanding Individual Choice and Control.” Many thanks to the reviewers for the quick turnaround.
Comparison of the Relationships between Serum Apolipoprotein B and Serum Lipid Distributions
Authors: Kim Byung Jin , Hwang Sang Tai , Sung Ki Chul , Kim Bum Soo , Kang Jin Ho , Lee Man Ho , Park Jung Ro 
Published: October 2005

AbstractBackground: Apolipoprotein B (apo B) has been reported to be a better predictor of coronary artery disease than cholesterol indices. The objectives of this study were to evaluate concordances/discordances between cholesterol indices and apo B and to assess the factors that influence them.Methods: For this study, 11 816 individuals (6965 males, 4851 females), none of whom had a past history of coronary artery disease, were selected from among visitors to the health promotion center at Kangbuk Samsung Hospital between January and December 2002. We assessed concordances between the biochemical indices of atherogenicity and evaluated factors associated with discordances.Results: Apo B and various cholesterol indices were correlated, although concordance fell within the range 47%–56%. Multinomial logistic regression analysis showed an increasing risk of a disproportionately higher apo B than LDL-cholesterol in males, the elderly, smokers, individuals with metabolic syndrome, in those with high HDL-cholesterol or triglyceride (TG) concentrations or larger waist circumferences, and in those with low total cholesterol (TC).Conclusions: The introduction of apo B to standard lipid profile testing could improve the evaluation of risk factors of coronary artery disease and aid more accurate assessment of the effects of cholesterol-lowering therapy, particularly in males, the elderly, smokers, or in individuals with metabolic syndrome, high HDL-cholesterol, high TGs, larger waist circumferences, or low TC.
The Efficacy of Hormone Assays in the Differential Diagnosis of Amenorrhea and Menopause
Authors: Chiecchio Andrea , Malvano Renzo , Vignati Giulio 
Published: October 2005

Abstract
The differential diagnosis of menopause and amenorrhea
is currently based on the assay of circulating follicle
stimulating hormone, luteinising hormone, and
estradiol. The diagnostic performance of the three hormone
assays, both as single and combined tests, was
evaluated considering as reference data the results
from 300 subjects for either condition, and assuming
menopause – amenorrhea prevalence ratios corresponding
to 1 and 10. In the calculation an “allocation”
scheme was adopted, and the uncertainty associated
with the diagnostic performance parameters was accounted
for. The results obtained clearly demonstrate
that the addition of a test for luteinising hormone or
estradiol (or both) to the testing for follicle stimulating
hormone is not justified in terms of improvement of
the diagnostic information.
Peripheral Pathways Regulate Motoneuron Collateral Dynamics
Authors: Redett Richard , Jari Rajesh , Crawford Thomas , Chen You-Gang , Rohde Charles , Brushart Thomas M. 
Published: October 2005

Motor axons regenerating after repair of mixed nerve reinnervate pathways leading to muscle more often than those leading to skin [preferential motor reinnervation (PMR)]. Motoneurons that initially project collaterals to both muscle and skin prune incorrect projections to generate specificity. The number of motor axon collaterals maintained entirely within cutaneous or muscle pathways, however, is unknown. To overcome this shortcoming, dorsal root ganglion excision has been used to allow only motor axons to regenerate after a peripheral lesion. Motor axon number in reinnervated cutaneous and muscle pathways can then be correlated with the number of parent motoneurons determined by retrograde labeling. The number of collaterals per neuron can be calculated for each environment and the relative roles of pathway and end organ assessed by blocking the distal pathways to prevent target reinnervation.Without sensory competition, PMR develops in two stages: a limited response to muscle nerve and then a robust response to muscle that may involve retrograde signaling to the proximal pathway. Motoneurons maintain more collaterals in cutaneous nerve than in muscle nerve, even without muscle contact. This difference could result either from increased collateral formation in cutaneous nerve or from increased collateral pruning in muscle nerve. In either instance, these findings confirm that muscle and cutaneous pathways have functionally significant identities that can be recognized by motor axons and can regulate their arborization. Decreased arborization in muscle pathways could promote regeneration by focusing neuronal resources on high-yield projections; increased arborization in cutaneous pathways, conversely, would enhance pathfinding abilities.