bluuebunny/crossref_metadata_2025_split huggingface dataset:
β‐Amyloid immunization approaches for Alzheimer's disease
Authors: Imbimbo Bruno P. 
Published: October 2002

AbstractAlzheimer's disease (AD) represents the third leading cause of death in the U.S. and the leading cause of dementia in the elderly population. Until recently, there was little hope of efficiently combating this devastating disease. The deposition of β‐amyloid (Aβ) is the major pathological hallmark of AD brains. Genetic, biochemical, and pharmacological evidence support the hypothesis that Aβ plays a key role in the development of the disease. Thus, in the last 5 years a number of pharmacological strategies have been developed to interfere with the Aβ cascade. The most revolutionary of these approaches was proposed in 1999 by scientists at Elan Pharmaceuticals, which immunized against Aβ transgenic mice with spontaneously developing Aβ pathology. The immunization was achieved by subcutaneous injections of a preaggregated form of the synthetic human 42‐amino acid Aβ emulsified with Freund's adjuvant, an immune stimulant. The vaccination caused a near complete inhibition of Aβ plaque formation in younger animals and a marked reduction of the Aβ burden in older animals. The effects on Aβ plaques were accompanied by a reduction of Aβ‐associated astrogliosis and neuritic dystrophy. These results were later confirmed by other groups with similar vaccination protocols, which also demonstrated that the Aβ immunization of transgenic animals normalize or reduce the cognitive impairment associated with Aβ pathology. Interestingly, effective removal of brain Aβ plaques was also obtained by peripherally administering Aβ antibodies. The mechanism with which the vaccine increases Aβ clearance is not fully understood. Centrally, the vaccine appears to activate Aβ phagocytosis by microglial monocytes. Peripherally, serum Aβ antibodies bind and sequester Aβ, thus altering its equilibrium between CNS and plasma. The dramatic results obtained in animal models of AD raised unprecedented hopes for both a preventive and a curative intervention for this devastating disorder. A vaccine preparation for human use (AN‐1792) composed of preaggregated human Aβ42 peptide and a highly purified saponin derivative (QS‐21) was developed by Elan Pharmaceuticals and Wyeth Ayerst and tested in AD patients. Unfortunately, a Phase IIa study aimed at evaluating the safety and immunological activity of AN‐1792 in 360 AD patients was discontinued because 15 subjects receiving the vaccine developed serious signs of CNS inflammation. Both central activation of cytotoxic T cells and autoimmune reactions were proposed as potential mechanisms of toxicity. Other therapeutic Aβ vaccination strategies are being pursued, including immuno‐conjugates and monoclonal antibodies. The future of these and other Aβ immunization approaches depend on a clear understanding of the mechanism of Aβ clearance and additional insight into the role of inflammation in the AD brain. Drug Dev. Res. 56:150–162, 2002. © 2002 Wiley‐Liss, Inc.
Secretases as targets for beta‐amyloid lowering drugs
Authors: Walter Jochen , Haass Christian 
Published: October 2002

AbstractAlzheimer's disease is characterized by the accumulation of neuritic plaques in the brain parenchyma. These plaques contain fibrillar forms of the amyloid β‐peptide (Aβ), which derives from the β‐amyloid precursor protein (βAPP) by proteolytic processing. It is now commonly believed that Aβ plays a crucial role in the pathogenesis of AD, and inhibition of its production is therefore a rational strategy to treat or prevent the disease. Substantial progress has been made in deciphering the molecular mechanisms underlying Alzheimer's disease (AD). In particular, with β‐secretase and the presenilins, two essential factors in the proteolytic generation of Aβ have been identified. Inhibitors of these proteins have already been developed and might serve as lead compounds for Aβ‐lowering drugs of clinical use. Drug Dev. Res. 56, 201–210 2002. © 2002 Wiley‐Liss, Inc.
The impact of recent climate change on flooding and sediment supply within a Mediterranean mountain catchment, southwestern Crete, Greece
Authors: Maas Glenn. S. , Macklin Mark. G. 
Published: October 2002

AbstractThis paper presents work from a geomorphological investigation carried out in the Aradena Gorge, southwestern Crete, Greece. The gorge is typical of many steepland fluvial systems in the Mediterranean, with steep relief, coarse‐gravel sediments and high rates of sedimentation generated during intense winter storm events. Hillslope deposits and coarse‐gravel flood units within a 5 km section of the gorge have been mapped, dated (using lichenometry and dendrochronology), and their sedimentological characteristics recorded to establish a c. 200‐year record of flood frequency/magnitude and hillslope/channel sediment supply variability. This record has been compared with instrumented and previously published records of climate change from Crete and the Mediterranean region and used to establish the major controls on flooding and sediment dynamics within the Aradena Gorge.Rates of colluviation and sediment delivery to the channel appear to have been greater than the present sometime before c. AD 1800 and may be related to cooler climates with a more seasonal precipitation regime during the Little Ice Age (c. AD 1450 to 1850). In gorge sections where the present rate of sediment supply from hillslope colluvium is very low, the channel has incised into older alluvial and colluvial deposits. Conversely, in the few sections where sediment supply is currently very high, the channel is aggrading with a braided pattern. Major rock‐fall deposits at certain locations in the gorge have restricted any major downstream sediment transfer.Twelve periods of increased flooding during the last 150 years have been identified and these correlate quite well with negative or declining phases of the North Atlantic Oscillation (NAO). Analysis of daily precipitation data from Crete suggests negative phases of the winter NAO are characterized by an increase in the number of long‐duration, high‐intensity storms. These storms, particularly those with five‐day and greater duration, appear to be significant in triggering major floods in the Aradena Gorge. During the last 40 years the NAO index has been increasing and become locked into a positive phase. As a consequence of this, major flooding appears to have declined during the same period. Copyright © 2002 John Wiley & Sons, Ltd.
Genetic alterations in cervical carcinomas: Frequent low‐level amplifications of oncogenes are associated with human papillomavirus infection
Authors: Zhang Anju , Månér Susanne , Betz Regina , Ångström Tord , Stendahl Ulf , Bergman Frank , Zetterberg Anders , Wallin Keng‐Ling 
Published: October 2002

AbstractThe development of cervical carcinoma is closely associated with HPV infection. However, other genetic alterations also play an important role. In this study, we analyzed copy number alterations of several oncogene loci in a panel of 84 cervical tumors. Sixty‐five (77%) tumors were HPV DNA‐positive, and most were infected with type 16 or type 18 or both. The oncogenes studied include PIK3CA at 3q26.3, TERT at 5p15.33, C‐MYC at 8q24, CCND1 at 11q13.3, ERBB2 at 17q21.2 and locus region 20q13.2. Amplification of 1 or more genes was detected in 55 (65%) cases using interphase FISH. PIK3CA was amplified in 43% of tumors, followed by TERT (33%), 20q13.2 (30%), ERBB2 (29%), C‐MYC (25%) and CCND1 (12%). Most tumors showed low‐level amplification with 3–7 copies of these genes, and complex changes involving 3 or more genes occur more frequently in tumors at advanced stages. Increased protein expression of c‐erbB2 and c‐myc was observed in tumors with the corresponding gene amplification. Oncogene alterations were found more often in HPV‐infected cases, particularly for C‐MYC and TERT. These findings indicate that HPV‐associated cervical carcinomas bear frequent alterations of these genes, which may have critical biologic impact on the development and progression of carcinoma of the uterine cervix. © 2002 Wiley‐Liss, Inc.
CHIMERA: A software tool for reaction rate calculations and kinetics and thermodynamics analysis
Authors: Novoselov Konstantin P. , Shirabaikin Denis B. , Umanskii Stanislav Ya. , Vladimirov Alexander S. , Minushev Airat Kh. , Korkin Anatoli A. 
Published: October 2002

AbstractThis article presents and overviews the CHIMERA program package, which provides a user‐friendly graphical interface between quantum chemistry and chemical kinetics programs. CHIMERA facilitates calculations of rate constants for gas‐phase reactions using transition state and Rice–Ramsperger–Kassel–Marcus theories. The program includes computational modules for simulation of gas‐phase kinetics using simplified reactor models and for computation of chemical equilibria. The review includes a description of the theory implemented in the code, the program description, the general strategy of calculations using CHIMERA, and illustrative examples of the program application. © 2002 Wiley Periodicals, Inc. J Comput Chem 14: 1375–1389, 2002
Molecular epidemiology of human calicivirus gastroenteritis outbreaks in Hungary, 1998 to 2000
Authors: Reuter Gábor , Farkas Tibor , Berke Tamás , Jiang Xi , Matson David O. , Szücs György 
Published: October 2002

AbstractBetween November 1998 and November 2000, 196 stool specimens from 21 outbreaks of acute nonbacterial gastroenteritis occurring in 11 of the 19 counties of Hungary were collected and tested for human caliciviruses. Human caliciviruses were detected and characterized by a type‐common enzyme‐linked immunosorbent assay (EIA) and reverse transcription‐polymerase chain reaction (RT‐PCR) followed by cloning and sequencing. Twenty (95%) and 14 (67%) outbreaks were positive by EIA and RT‐PCR, respectively, and 12 RT‐PCR‐positive outbreaks were also confirmed by sequencing. Comparative sequence analysis revealed 13 Norwalk‐like virus sequences in the 12 outbreaks, including 11 Norwalk‐like virus genogroup II (seven in Hawaii‐like, two Lordsdale‐like, one Melksham‐like, and one Hillingdon‐like) and two Norwalk‐like virus genogroup I (related to Southampton‐like and Desert Shield‐like clusters) viruses. Multiple Norwalk‐like virus clusters, with a predominance of Hawaii‐like viruses, played an important role in nonbacterial gastroenteritis outbreaks during the study period. This is the first country‐wide molecular epidemiological investigation of human calicivirus‐associated, gastroenteritis outbreaks in Hungary and Central‐Eastern Europe. J. Med. Virol. 68:390–398, 2002. © 2002 Wiley‐Liss, Inc.
Relative importance of stakeholders: analysing speech acts in a layoff
Authors: Guild Wendy L. 
Published: October 2002

AbstractGrounded in a participant observation study of a ski resort, this paper explores the (re)production of legitimate discourses through speech acts pertaining to an organizational event, a layoff. Manager's justifications and employees' reactions and critiques put sanctioned discourses into play. And while the stated organizational values include shareholder, customer, and employee concerns, the relative importance of these stakeholders is only made clear through the conversation of the speech acts and their reception. The shape of the conversation, in locution, illocution and perlocution, shifts the relations between managers and the employees and creates longer term consequences for the organization. This focus on language use serves as a micro‐foundation for the study of legitimation processes and its consequences within organizations. Copyright © 2002 John Wiley & Sons, Ltd.
Measurement of adhesive forces between S. epidermidis and fibronectin‐coated surfaces using optical tweezers
Authors: Simpson Kathryn Hicks , Bowden M. Gabriela , Höök Magnus , Anvari Bahman 
Published: October 2002

AbstractBackground and ObjectivesBiomaterial‐mediated infection, a common cause of medical device failure, is initiated by bacterial adhesion to an adsorbed protein layer on the implant surface. This adhesion is thought to be mediated by specific molecules present on the bacterial cell surface. Optical tweezers can be used to measure the adhesive force between a single bacterium and a protein‐coated surface.Study Design/Materials and MethodsUsing optical tweezers, a bacterium was trapped and brought in contact with a 10‐μm diameter polystyrene microsphere coated with fibronectin. The minimum force required to detach the cell from the bead was determined over a range of fibronectin concentrations and contact times.ResultsThe detachment forces were integer multiples of an 18‐pN base value that was independent of contact time and coating concentration; we propose that the variation in force is related to the number of bonds formed.ConclusionsThese experiments demonstrate that optical tweezers can be used to investigate the adhesion of individual bacteria to surfaces. The results suggest that S. epidermidis has surface proteins capable of binding fibronectin. Lasers Surg. Med. 31:45–52, 2002. © 2002 Wiley‐Liss, Inc.
Effect of Er:YAG laser on bond strength to dentin of a self‐etching primer and two single‐bottle adhesive systems
Authors: Ramos Renata P. , Chimello Daniela T. , Chinelatti Michelle A. , Nonaka Tomio , Pécora Jesus D. , Palma Dibb Regina G. 
Published: October 2002

AbstractBackground and ObjectivesTo assess the effect of erbium:yttrium aluminium garnet (Er:YAG) laser on bond strength to dentin of a self‐etching primer (Clearfil Liner Bond 2V, CL2V) and two single‐bottle agents (Excite, EX; Gluma One Bond, GB).Study Design/Materials and MethodsThirty human molars were selected, roots were removed and crowns were bisected, providing 60 halves. Specimens were included and ground to expose dentin. Bonding site was limited and samples were assigned to three groups: I, CL2V; II, EX; III, GB. Dentin was either conventionally treated or submitted to laser conditioning + conventional treatment. The adhesive protocol was performed, samples were stored for 24 hours and bond strength was tested to failure (0.5 mm/min).ResultsStatistical analysis showed a decrease in bond strength for lased subgroups and this drop was more evident for EX. CL2V provided the best overall results, regardless of the surface treatment.ConclusionsEr:YAG laser may adversely affect bond strength in higher or lesser degree, depending on the adhesive system used. Lasers Surg. Med. 31:164–170, 2002. © 2002 Wiley‐Liss, Inc.
Protein serine and threonine phosphorylation, hyperactivation and acrosome reaction in in vitro capacitated hamster spermatozoa
Authors: Jha Kula Nand , Shivaji S. 
Published: October 2002

AbstractMonoclonal antibodies against phosphoserine and phosphothreonine were used in the present study to investigate the changes in serine and threonine phosphorylation respectectively during capacitation of hamster spermatozoa. Immunoblot analysis of hamster spermatozoa capacitated in TALP, a medium that supports capacitation, showed that a set of four proteins of molecular weight 56, 63, 66, and 100 kDa was phosphorylated both at the serine and threonine residues. In addtion, five other proteins of molecular weight 32, 39, 45, 53, and 61 kDa were phosphorylated specifically at the threonine residues. Of these nine proteins, the 100 kDa protein showed a time dependent or capacitation‐dependent decrease in intensity which coincided with the percentage acrosome‐reacted spermatozoa. In contrast, the 49 and 63 kDa threonine phosphorylated proteins showed increased phosphorylation coinciding with capacitation. H8 (a serine and threonine kinase inhibitor) had a transient effect on the phosphorylation of these two phosphothreonine proteins but inhibited acrosome reaction substantially all through the treatment period. Okadaic acid (OA) (a serine and threonine protein phosphatase inhibitor) inhibited hyperactivation but had no effect on acrosome reaction. In fact, OA stimulated acrosome reaction. Finally the immunofluorescence studies indicated localization of the serine phosphorylated proteins in tail as well as in head of the capacitated hamster spermatozoa whereas the threonine phosphorylated proteins were localized mostly in the tail of the spermatozoa. The findings of the present study suggest that serine/threonine phosphorylation and the enzymes responsible for regulating the level of phosphorylation play an important role in capacitation and capacitation‐associated events namely hyperactivation and acrosome reaction. However, further studies are needed in order to establish the exact role of these proteins in capacitation of spermatozoa. Mol. Reprod. Dev. 63: 119–130, 2002. © 2002 Wiley‐Liss, Inc.
Inheritance of resistance of bovine preimplantation embryos to heat shock: Relative importance of the maternal versus paternal contribution
Authors: Block J. , Chase C.C. , Hansen P.J. 
Published: October 2002

AbstractBrahman preimplantation embryos are less affected by exposure to heat shock than Holstein embryos. Two experiments were conducted to test whether the ability of Brahman embryos to resist the deleterious effects of heat shock was a result of the genetic and cellular contributions from the oocyte, spermatozoa, or a combination of both. In the first experiment, Brahman and Holstein oocytes were collected from slaughterhouse ovaries and fertilized with spermatozoa from an Angus bull. A different bull was used for each replicate to eliminate bull effects. On day 4 after fertilization, embryos ≥ 9 cells were collected and randomly assigned to control (38.5°C) or heat shock (41°C for 6 hr) treatments. The proportion of embryos developing to the blastocyst (BL) and advanced blastocyst (ABL; expanded and hatched) stages was recorded on day 8. Heat shock reduced the number of embryos produced from Holstein oocytes that developed to BL (P < 0.001, 55.6 ± 4.2% vs. 29.8 ± 4.2%) and ABL (P < 0.01, 37.7 ± 3.6% vs. 12.2 ± 3.6%) on day 8 as compared to controls. In contrast, heat shock did not reduce development of embryos produced from Brahman oocytes (BL = 42.1 ± 4.8% vs. 55.6 ± 4.8% for 38.5 and 41°C, respectively; ABL = 17.6 ± 4.2% vs. 32.4 ± 4.2%). In the second experiment, oocytes from Holstein cows were fertilized with semen from bulls of either Brahman or Angus breeds. Heat shock of embryos ≥ 9 cells reduced development to BL (P < 0.002) and ABL (P < 0.005) for embryos sired by both Brahman (BL = 54.3 ± 7.7% vs. 23.4 ± 7.7%; ABL = 43. ± 7.4% vs. 7.9 ± 7.4%, for 38.5 and 41°C, respectively) and Angus bulls (BL = 57.9 ±  7.7% vs. 31.0 ± 7.7%; ABL = 33.6 ± 7.4% vs. 18.4 ± 7.4%, for 38.5 and 41°C, respectively). There were no breed × temperature interactions. Results suggest that the oocyte plays a more significant role in the resistance of Brahman embryos to the deleterious effects of heat shock than the spermatozoa. Mol. Reprod. Dev. 63: 32–37, 2002. © 2002 Wiley‐Liss, Inc.
HPLC analysis of fusaric acid, 9,10‐dehydrofusaric acid and their methyl esters, toxic metabolites from weed pathogenic Fusarium species
Authors: Amalfitano Carmine , Pengue Raffaele , Andolfi Anna , Vurro Maurizio , Zonno Maria C. , Evidente Antonio 
Published: October 2002

AbstractA simple and rapid HPLC method, using a high‐density C18 column, has been developed for the quantitative analysis of fusaric and dehydrofusaric acids and their methyl esters in the methanol extract of lyophilised culture filtrates of species of Fusarium. The method has been used to determine the content of these metabolites in two strains of Fusarium oxysporum and in strains of F. nygamai and F. udum. Fusaric acid has been isolated and identified from a strain of F. udum for the first time. Copyright © 2002 John Wiley & Sons, Ltd.
Initiation mechanisms of an anionic ring‐opening polymerization of lactam‐12
Authors: Luisier A. , Bourban P.‐E. , Månson J.‐A. E. 
Published: October 2002

AbstractA novel liquid system has been developed to initiate the anionic polymerization of lactam‐12. This system, containing both an activator and a catalyst, has the primary advantage over previous systems of permitting infinite storage of the reactant, and it avoids premixing of batches. The anionic species of the system were identified with matrix‐assisted laser desorption/ionization time‐of‐flight measurements, and Fourier transform infrared was used to measure the change in their concentrations during the polymerization. A guanidine anion was formed, and the system initiated the polymerization by this guanidine and by the catalyst. The kinetics of the anionic polymerization of lactam‐12 into polyamide‐12 were followed with differential scanning calorimetry measurements. The determined reaction rates indicated that this liquid system was particularly well suited for initiating in situ polymerization during liquid molding. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3406–3415, 2002
Non‐native interactions, effective contact order, and protein folding: A mutational investigation with the energetically frustrated hydrophobic model
Authors: Treptow Werner L. , Barbosa Marco Aurélio A. , Garcia Leandro G. , Pereira de Araújo Antônio F. 
Published: October 2002

AbstractBy Monte Carlo simulations, we explored the effect of single mutations on the thermodynamics and kinetics of the folding of a two‐dimensional, energetically frustrated, hydrophobic protein model. Φ‐Value analysis, corroborated by simulations beginning from given sets of judiciously chosen initial contacts, suggests that the transition state of the model consists of a limited region of the native structure, that is, a folding nucleus. It seems that the most important contacts in the transition state (large and positive Φ) are not the ones with the highest contact order, because in this case the entropic cost of their formation would be too high, but exactly the ones that decrease the entropic cost of difficult contacts, reducing their effective contact order. Mutations of internal monomers involved in high‐order contacts were actually the ones resulting in the fastest kinetics (and Φ < 0), indicating they tend to make low order, non‐native contacts of low entropic cost that stabilize the unfolded state with respect to the transition state. Folding acceleration by other non‐native interactions was also observed and a simple general mechanism is proposed according to which non‐native contacts can act indirectly over the folding nucleus, “chelating” out potentially harmful contacts. The polymer graph of our model, which facilitates the visualization of effective contact orders, successfully suggests the relative kinetic importance of different contacts and is reasonably consistent with analogous graphs for the well characterized family of SH3 domains. Proteins 2002;49:167–180. © 2002 Wiley‐Liss, Inc.
Anisotropic effective interactions in a coarse‐grained tube picture of proteins
Authors: Banavar Jayanth R. , Maritan Amos , Seno Flavio 
Published: October 2002

AbstractRecent studies have shown that a coarse‐grained description of a protein backbone represented as a tube of non‐zero thickness captures many of the common characteristics of small globular proteins. Here we argue that such a physical picture leads to a prediction of inherently anisotropic amino acid interactions. In order to test this prediction, we have carried out an extensive analysis of a data bank made up of 600 proteins with low sequence homology and covering many different three‐dimensional folds. This analysis, based on the study of the geometrical properties of the vectors joining next‐nearest neighbor Cα atoms along the chain, shows clearly that when amino acids are in contact, the distribution of their relative orientations is not random but exhibits peaks at specific angles whose values reflect, in general, the tubular nature of proteins and, more specifically, the nature of the secondary structure motifs, which are the building blocks of protein structures. Our results suggest that the incorporation of the relative orientation of amino acids in contact could play a vital role in simplified coarse‐grained schemes for determining effective interaction parameters for use in folding, threading, and docking. Proteins 2002;49:246–254. © 2002 Wiley‐Liss, Inc.