bluuebunny/crossref_metadata_2025 huggingface dataset:
Is there a rational method to purify proteins? From expert systems to proteomics
Authors: Asenjo J. A. , Andrews B. A.
Published: April 2004

The purification of recombinant proteins for therapeutic or analytical applications requires the use of several chromatographic steps in order to achieve a high level of purity. A range of techniques is available such as anion and cation exchange chromatography, which can be carried out at different pHs, and hence used at different steps, hydrophobic interaction chromatography, gel filtration and affinity chromatography. Evidently when confronted with a complex mixture of partially unknown proteins or a clarified cell extract there are many different routes one can take in order to choose the minimum and most efficient number of purification steps to achieve a desired level of purity (e.g. 98, 99.5 or 99.9%). In this review we will show how an initial ‘proteomic’ characterization of the complex initial mixture of target protein and protein contaminants can be used to select the most efficient chromatographic separation steps in order to achieve a maximum level of purity with a minimum number of steps. The chosen methodology was implemented in a computer based expert system. The first algorithm developed was used to select the most efficient purification method to separate a protein from its contaminants based on the physicochemical properties of the protein product and the protein contaminants. The second algorithm developed was used to predict the number and concentration of contaminants after each separation as well as protein product purity. The successful application of the expert system approach, based on an initial proteomic characterization, to the practical cases of protein mixtures and clarified fermentation supernatant is presented and discussed. The purification strategy proposed was experimentally tested and validated with a mixture of four proteins and the experimental validation was also carried out with an ‘unknown’ supernatant of Bacillus subtilis producing a recombinant β‐1,3‐glucanase. The system was robust to errors <10% which is the range that can be found in the experimental determination of the properties in the database of product and contaminants. On the other hand, the system was sensitive both to larger variations (>20%) in the properties of the contaminant database and the protein product and to variations in one protein property (e.g. hydrophobicity). Copyright © 2004 John Wiley & Sons, Ltd.
Enhancement of Productivity, Molecular Weight and Stereoregularity of 1‐Butene Polymerization by MAO Modification
Authors: Fujita Masayuki , Seki Yoshinori , Miyatake Tatsuya
Published: April 2004

Summary: The modification of MMAO using water and pentafluorophenol enhances the productivity, molecular weight, regioregularity and stereoregularity of the polymer obtained from the polymerization of 1‐butene with TBPTiCl2. The structural changes in water modified‐MMAO (WM‐MMAO) and water/pentafluorophenol‐modified‐MMAO (W/PM‐MMAO) were revealed by 27Al MAS NMR. Although only 4‐ and 6‐coordinated aluminium species existed in the MMAO, a new peak derived from a 5‐coordinated Al species appeared when the water or water/phenol modification was carried out. This result suggests that a 5‐coordinated aluminium species of WM‐ or W/PM‐MMAO might significantly influence the behavior of the single‐site catalyst.

Structure of the here used catalyst.

image

Structure of the here used catalyst.
Surface Aspects in Fatigue of Shape Memory Alloys (SMA)
Authors: Hornbogen E. , Eggeler G.
Published: April 2004

The present paper briefly reviews the role of surfaces in fatigue of shape memory alloys (SMAs). When polished and defect free austenitic surfaces are cooled to lower temperatures, the martensitic transformation creates a pattern of surface upheavals; and an inverse pattern forms when polished and defect free martensite is heated. In full transformation cycles (heating followed by cooling or cooling followed by heating) high quality surfaces can only be re‐established if no fatigue occurs. After multiple cycling intrusions and extrusions can be detected which represent fatigue damage accumulation. Cracks can grow from extrusions and intrusions. We also show that fatigue cracking can start from surface defects which are for example introduced by wire drawing. We then briefly discuss surface treatments which are intended to improve fatigue resistance of shape memory alloys. These may consist in the modification of the SMA microstructure in the surface region (by deformation or diffusion treatments). They can also involve coating procedures where other elements are deposited on the SMA surface. However, SMA performance and the intensity of exploitable SM effects are usually reduced by surface treatments.
Phrenic nerve transfer in the treatment of brachial plexus avulsion: An experimental study of nerve regeneration and muscle morphology in rats
Authors: Zhang Cheng‐Gang , Ma Jian‐Jun , Terenghi Giorgio , Mantovani Cristina , Wiberg Mikael
Published: April 2004

The regeneration of motor and sensory neurons and the morphological changes of the target muscle after phrenic nerve transfer were investigated in adult rats. Six months following nerve transfer, 326.0 ± 16.31 phrenic motoneurons regenerated into musculocutaneous nerve, which is not different from the normal number of phrenic motoneurons. The regenerated motoneurons exhibited a 14% nonsignificant hypertrophy. Of the dorsal root ganglia (DRG) neurons, 255.8 ± 45.26 regenerated, which was significantly lower than the number of normal phrenic DRG neurons. The regenerated phrenic DRG neurons showed a 24% close‐to‐significant atrophy. The target muscle fiber morphology changed considerably after reinnervation. The present results suggest that the phrenic nerve has very good regenerative ability in terms of its motoneurons and a relatively insufficient sensory neuronal regeneration. © 2004 Wiley‐Liss, Inc.
Large‐scale local search heuristics for the capacitated vertex p‐center problem
Authors: Scaparra Maria Paola , Pallottino Stefano , Scutellà Maria Grazia
Published: April 2004

This article investigates the application of very large neighborhood search techniques for solving the capacitated vertex p‐center problem. We characterize a local search neighborhood in terms of path and cyclic exchanges of customers among facilities, and exploit principles borrowed from network optimization theory to efficiently detect cost‐decreasing solutions in such a neighborhood. We complement the multiexchange methodology with a relocation mechanism specifically designed to perform facility location adjustments. The validity of the proposed approach is supported by empirical investigation and performance comparisons with the commercial code CPLEX. © 2004 Wiley Periodicals, Inc.
Thermotropic liquid‐crystalline polyesters containing biphenyl mesogens in the main chain: The effect of connectivity
Authors: Ranganathan T. , Ramesh C. , Kumar Anil
Published: April 2004

A homologous series of main‐chain thermotropic liquid‐crystalline polyesters containing rigid biphenyl mesogen and flexible methylene spacers were synthesized with the AB‐type self‐polycondensation approach. The polyesters were characterized with 1H NMR, gel permeation chromatography, thermogravimetric analysis, differential scanning calorimetry, polarized light optical microscopy, and X‐ray diffraction. These polyesters, containing trimethylene spacers on the acid side and various spacers on the alcohol side of the biphenyl mesogen, showed an odd–even effect in the transition temperatures and mesophase type. The even members showed higher transition temperatures than the odd ones. A normal smectic mesophase was observed for the even members, whereas the odd‐membered counterparts exhibited a tilted smectic mesophase. To study the effect of connectivity, the mesophase characteristics of these polyesters were compared with those of the isomeric AB‐type polyesters without any methylene spacer on the acid side of the biphenyl moiety. The mesophase characteristics were insensitive to whether the mesogen was connected to a carboxyl unit or a methylene unit. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2734–2746, 2004
Polyesterification of aromatic dicarboxylic acids and bisphenols with tosyl chloride/dimethylformamide/pyridine promoted by the improvement of the difficult solubility of the activated diacids with lithium chloride
Authors: Higashi Fukuji , Kira Kaori
Published: April 2004

The solution polyesterification of dicarboxylic acids in pyridine, the activated intermediates of which were difficult to dissolve in tosyl chloride/dimethylformamide/pyridine, was investigated in the presence of lithium chloride. The solubility of the activated dicarboxylic acids was largely improved by the presence of the salt, and the polycondensation with bisphenols was greatly facilitated. The salt was more effectively added to a pyridine solution of dicarboxylic acids than to the activated dicarboxylic acids in pyridine. The favorable additive effect on the improved solubility was attributed to a lowered degree of association of the activated dicarboxylic acids, which led to distributions of the resulting oligomers from bisphenols at an earlier stage closer to the theoretical ones and yielded better polycondensation results. The reaction, which proceeded through favorable distributions of the co‐oligomers, produced copolymers of higher inherent viscosities and slightly block sequence distributions determined by NMR. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2725–2733, 2004
SEN virus infection
Authors: Sagir Abdurrahman , Kirschberg Oliver , Heintges Tobias , Erhardt Andreas , Häussinger Dieter
Published: April 2004

The SEN virus (SEN‐V) belongs to a recently discovered group of DNA viruses whose members (SEN‐V‐D and SEN‐V‐H) are associated with post‐transfusion hepatitis. It is a single‐stranded circular, non‐enveloped DNA virus of ∼3600 to ∼3800 nucleotides with at least three open reading frames (ORFs). Eight different strains of SEN‐V have been identified and provisionally classified as members of the Circoviridae family, a group of small, single‐stranded, non‐enveloped circular DNA viruses that includes the TT virus (TTV), TUS01, SANBAN, PMV and YONBAN. Prevalences in different populations show great variability with marked differences between different countries and groups. Although parenteral transmission is very likely, other routes of transmission cannot be excluded. Mother to infant transmission has been demonstrated. The effect of SEN‐V on chronic liver diseases has been studied. The influence of SEN‐V on the response to HCV therapy was investigated in three studies, with contradictory results. Data for other acute and chronic liver diseases are sparse. Further studies are needed to define the pathogenesis and clinical importance of SEN‐V infection. Copyright © 2004 John Wiley & Sons, Ltd.
Building uniformly random subtrees
Authors: Luczak Malwina , Winkler Peter
Published: April 2004

We prove the existence of, and describe, a (random) process which builds subtrees of a rooted d‐branching tree one node at a time, in such a way that the subtree created at stage n is precisely a uniformly random subtree of size n. The union of these subtrees is a “uniformly random” infinite subtree, which we describe and generate in several ways. Generalization to generation of other combinatorial structures is also considered. © 2004 Wiley Periodicals, Inc. Random Struct. Alg., 2004
Does the Prentice criterion validate surrogate endpoints?
Authors: Berger Vance W.
Published: April 2004

Randomized Phase II or Phase III clinical trials that are powered based on clinical endpoints, such as survival time, may be prohibitively expensive, in terms of both the time required for their completion and the number of patients required. As such, surrogate endpoints, such as objective tumour response or markers including prostate specific antigen or CA‐125, have gained widespread popularity in clinical trials. If an improvement in a surrogate endpoint does not itself confer patient benefit, then consideration must be given to the extent to which improvement in a surrogate endpoint implies improvement in the true clinical endpoint of interest. That this is not a trivial issue is demonstrated by the results of an NIH‐sponsored trial of anti‐arrhythmic drugs, in which the ability to correct an irregular heart beat not only did not correspond to a survival benefit but in fact led to excess mortality. One approach to the validation of surrogate endpoints involves ensuring that a valid between‐group analysis of the surrogate endpoint constitutes also a valid analysis of the true clinical endpoint. The Prentice criterion is a set of conditions that essentially specify the conditional independence of the impact of treatment on the true endpoint, given the surrogate endpoint. It is shown that this criterion alone ensures that an observed effect of the treatment on the true endpoint implies a treatment effect also on the surrogate endpoint, but contrary to popular belief, it does not ensure the converse, specifically that the observation of a significant treatment effect on the surrogate endpoint can be used to infer a treatment effect on the true endpoint. Published in 2004 by John Wiley & Sons, Ltd.
Should statisticians reporting to data monitoring committees be independent of the trial sponsor and leadership?
Authors: Ellenberg Susan S. , George Stephen L.
Published: April 2004

It has long been a fundamental principle of clinical trials that interim comparative data should be kept confidential, with such data accessible only to a small number of individuals responsible for its analysis and monitoring. The rationale for keeping investigators and sponsors blinded to interim data has been extensively discussed, but the possible conflicts of interest that could arise for the statistician who performs the analysis of the interim data and presents it to a data monitoring committee has received little attention. We describe these potential conflicts, and the advantages and disadvantages of approaches that might be taken to minimize them. We have invited commentary on this issue from several statisticians with substantial experience in clinical trials and interim data monitoring. Published in 2004 by John Wiley & Sons, Ltd.
The independent statistician for data monitoring committees
Authors: DeMets David L. , Fleming Thomas R.
Published: April 2004

Clinical trials are an essential part of the clinical research process. Recently, independent Data Monitoring Committees (DMCs) have been widely implemented to provide scientific and ethical oversight of pivotal clinical trials having irreversible outcomes such as death, stroke, disease recurrence or a serious adverse event. To carry out their responsibility, the DMC reviews interim analyses of accumulating data. We address the motivation for having the preparation and presentation of these interim analyses be conducted by an independent statistician who is not a member of the DMC and who is not the trial's lead or steering committee statistician. These views are based on having served as members of many DMCs as well as having been the independent statistician for several trials. Copyright © 2004 John Wiley & Sons, Ltd.
Building KidPad: an application for children's collaborative storytelling
Authors: Hourcade Juan Pablo , Bederson Benjamin B. , Druin Allison
Published: April 2004

Collaborating in small groups can be beneficial to children's learning and socializing. However, there is currently little computer support for children's collaborative activities. This was our motivation for building KidPad, a collaborative storytelling tool for children. KidPad provides children with drawing, typing, and hyperlinking capabilities in a large, two‐dimensional canvas. It supports collaboration by accepting input from multiple mice. In building KidPad, we developed solutions to problems common to all single‐display groupware applications for children: using an intuitive user interface metaphor that can support collaboration, and obtaining input from multiple devices. We addressed the need for an appropriate user interface metaphor by using the local tools metaphor. In developing the concept of local tools we learned about the importance of addressing the issue of global modes. Our solution for obtaining input from multiple devices was MID, an architecture written in Java. In building MID, we learned about the importance of building flexible architectures that can support a wide range of applications and devices in a consistent manner, and that are easy to extend and use by programmers. This paper describes our work on local tools and MID in the context of building KidPad, and aims to provide developers with valuable insights into how to develop collaborative applications for children. Copyright © 2004 John Wiley & Sons, Ltd.
Developing a statewide faculty learning community program
Authors: Hansen Sheryl , Kalish Alan , Hall Wayne E. , Gynn Catherine M. , Holly Mary Louise , Madigan Dan
Published: April 2004

A small state agency used the FLC model to collaborate with campuses on faculty development efforts that resulted in successful implementation of pedagogically robust and technologically enhanced programs.
Technology in support of faculty learning communities
Authors: Vaughan Norman
Published: April 2004

Technology can be used to effectively support FLCs. This chapter explores how technology and a community of inquiry model can be used to facilitate individual reflection and critical discourse about teaching practice.
Quantitative major and trace elemental mapping by PIXE of concretionary pyrite from the Witwatersrand Basin, South Africa
Authors: Reimold W. U. , Przybylowicz W. J. , Gibson R. L.
Published: April 2004

Several concretionary pyrite grains displaying multiple, massive sulphide or silicate inclusion‐rich, annuli from two gold‐bearing reef horizons (Ventersdorp Contact Reef, Kimberley Reefs) in different parts of the Witwatersrand Basin were analysed by particle‐induced X‐ray emission (PIXE) and electron microprobe analysis (EMPA) for their major and trace element compositions. Both PIXE spot analysis and mapping of the distributions of major and trace elements were carried out, and EMPA was employed to obtain major element abundances for matrix corrections of PIXE analysis. Spatial analysis by PIXE is excellent in comparison with EMPA, as PIXE detection limits are lower by 1–2 orders of magnitude at comparable, short‐duration counting times (12 h for 4096 pixel analyses by PIXE). EMPA was successful in the identification of individual zones, for example on the basis of locally enriched minor elements Ni or As. This technique also provided essential standard‐based control on major element abundances for the standardless PIXE dynamic analysis. The compositional results obtained on concretionary pyrite grains by PIXE are distinctly different for each analysed grain, in terms of relative enrichment of certain minor and trace elements in specific zones. Gold was detected locally in the interiors of grains and/or along grain margins. The different results are discussed with regard to their possible meaning related to the origin of gold mineralization in the Witwatersrand ore deposit. Copyright © 2004 John Wiley & Sons, Ltd.
Practical normal form computations for vector fields
Authors: Mayer S. , Scheurle J. , Walcher S.
Published: April 2004

We present a method to compute a Poincaré‐Dulac normal form of a vector field, as well as a corresponding reduced vector field, near a stationary point with arbitrary linearization. Explicit knowledge of the eigenvalues of the linearization is not necessary, and only rational operations are required. Some examples are presented, including a normal form computation relevant for Hopf bifurcations, and coupled nonlinear oscillators.
European Markets and National Regulation: Conflict and Cooperation in British Competition Policy
Authors: ZAHARIADIS NIKOLAOS
Published: April 2004

The aim of this article is to examine the politics of competition policy in the United Kingdom by taking into account regulatory cooperation at the European Union level. Adopting a multiple streams approach, the article follows a bottom-up approach placing domestic politics at the heart of the puzzle. The analysis leads to four conclusions. First, pace-setters, such as the UK, may not be interested in playing one dimension of the regulatory competition game, that is, trying to influence the development of EU policy. Second, incongruence between domestic and EU regimes does not necessarily produce change at the domestic level. Convergence is not a top-down process. Third, the activating stimulus for change may be external (the EU), but the process is basially of domestic politics. Fourth, to the extent that the removal of political discretion characterizes a more transparent and strictly enforced regime, British competition policy provides empirical support for the hypothesis that the interaction of regulatory competition prior to regulatory cooperation leads to convergence to the top.
Glacial Lake Wright, a high-level Antarctic lake during the LGM and early Holocene
Authors: Hall B.L. , Denton G.H. , Overturf B.
Published: April 2004

We report evidence of a large proglacial lake (Glacial Lake Wright) that existed in Wright Valley in the McMurdo Dry Valleys region of Antarctica at the last glacial maximum (LGM) and in the early Holocene. At its highstands, Glacial Lake Wright would have stretched 50 km and covered c. 210 km2. Chronology for lake-level changes comes from 30 AMS radiocarbon dates of lacustrine algae preserved in deltas, shorelines, and glaciolacustrine deposits that extend up to 480 m above present-day lakes. Emerging evidence suggests that Glacial Lake Wright was only one of a series of large lakes to occupy the McMurdo Dry Valleys and the valleys fronting the Royal Society Range at the LGM. Although the cause of such high lake levels is not well understood, it is believed to relate to cool, dry conditions which produced fewer clouds, less snowfall, and greater amounts of absorbed radiation, leading to increased meltwater production.
Sims Island: first data from a Pliocene alkaline volcanic centre in eastern Ellsworth Land
Authors: Hathway B.
Published: April 2004

Although Sims Island (73°17′S/78°33′W), a bedrock peak in Carroll Inlet on the English Coast of eastern Ellsworth Land (Fig. 1), had previously been observed and photographed from the air (e.g. Rowley & Thomson 1990, fig. C.6.2), no landing had been made prior to the present study. Based on proximity and apparent lithological similarities, the island was thought likely to consist of alkaline volcanic rocks similar to those exposed on nearby Snow Nunataks (Fig. 1; e.g. Rowley & Thomson 1990). Smellie (1999) tentatively included it the Bellingshausen Sea Volcanic Group (BSVG), which consists of Miocene-Recent alkaline volcanic outcrops scattered across Alexander Island and eastern Ellsworth Land. More specifically, he provisionally assigned it to the Mount Benkert Formation (MBF), a probable subglacial volcanic succession exposed on three of the four Snow Nunataks. This note is based on observations made and samples collected during a short visit to Sims Island on 6 March 1996.
Vegetation abundance and diversity in relation to soil nutrients and soil water content in Vestfold Hills, East Antarctica
Authors: Leishman Michelle R. , Wild Christie
Published: April 2004

Eighteen paired sites (adjacent to vs away from sea bird nests) and six transects (downslope of nests) across Vestfold Hills were sampled for vegetation, soil nutrients, soil water content and percent rock cover. Three moss and 17 lichen species were recorded, including a new record for the lichen Sarcogyne privigna. Sites adjacent to nesting areas generally had higher soil N and P than sites away from nesting areas; however, larger differences between site locations than within site pairs suggests considerable variation in nutrient input between nesting areas and/or redistribution of nutrients by meltwater around nests. Along transects below nesting sites, average soil total N declined from 0.22% to 0.05% within 2 m from the nest, while average total P declined more gradually from 2343 ppm P to 697 ppm P at 30 m from the nest. Moss and lichen species diversity and mean lichen species abundance were higher in sites adjacent to compared with away from nests. Data from site pairs and transects showed that lichen diversity and abundance increased with increasing soil nutrients, with soil P having a stronger influence than soil N. In contrast, soil nutrients were not significantly associated with moss diversity or abundance. Instead, number of moss species and abundance were positively associated with soil water content.
Three-dimensional ice sheet structure at Dome C, central East Antarctica: implications for the interpretation of the EPICA ice core
Authors: Siegert Martin J. , Eyers Richard D. , Tabacco Ignazio E.
Published: April 2004

Airborne radar data acquired in 1995 by the Italian Antarctic Programme over Dome C in central East Antarctica were processed to develop maps of internal isochronous ice sheet layering around the EPICA ice core site. Three internal layers were traced continuously across the radar-survey area at ice depths of 1–2 km. The maps reveal that the ice core site is located where internal layers are near horizontal to depths of at least 2 km. The Italian radar data do not resolve internal layers below 2 km. However, radar data collected over this part of East Antarctica in the 1970s show the internal layers to depths of up to 4 km. These internal layers reveal the regional structure of ice to the west of Dome C. Layers from both surveys are dated through an existing chronostratigraphic link between the Vostok ice core site and Dome C. The pattern of internal layering at Dome C reflects relatively steady conditions of ice flow and accumulation for the last 100 000 years. However, for ice older than this we show that there is significant local variation in the thickness between internal layers and the ice-sheet base. Our maps provide an indication of the structure of the ice sheet from which the EPICA deep ice core will be taken.
A mechanism for swarming in the tunicate Salpa thompsoni (Foxton, 1961)
Authors: Daponte M.C. , Capitanio F.L. , Esnal G.B.
Published: April 2004

Two populations of Salpa thompsoni, collected from the Weddell–Scotia confluence area at the end of two summers (1994 and 1995) with contrasting densities, are compared. The present study was aimed at corroborating whether fluctuations in abundance could be related to some life history parameters considered as indicators of growth rate in salp populations, such as the body size of solitary reproductive individuals, number of buds per block or chain in the stolon, and the offspring to parent ratio. No differences were observed in the sizes reached by aggregate individuals, or in the size at which oocyte maturity was attained (moment at which the development of the embryo can be detected). There were no differences in the size reached by the embryos during their residence inside the mother's blastozooid. In 1995, the percentage of non-fecundated blastozooids (which included even the largest individuals) was higher than in 1994. The mean size of the solitary individuals was significantly higher in 1994 than in 1995. The number of buds per block was also significantly higher in most of the stages, confirming that this is the mechanism used by these organisms to produce swarms. This species eventually attains high population densities under favorable environmental conditions such as poor sea-ice cover in winter. Under optimal conditions, the number of potential descendants produced by a single solitary individual would exceed 800.
Intercomparison of firn core and meteorological data
Authors: McMorrow Alison J. , Curran Mark A.J. , Ommen Tas D. Van , Morgan Vin , Pook Michael J. , Allison Ian
Published: April 2004

High resolution firn core records of the oxygen isotope ratio (δ18O) and trace chemical species were extracted from a high accumulation site on Law Dome, East Antarctica. Inter-core comparisons were conducted and regional events identified in cores 5 km apart. High resolution dating of one of the firn cores was established using a co-located Automatic Weather Station (AWS) equipped with a snow accumulation sensor, allowing dating of individual precipitation events in the firn core record. Variations in the δ18O and trace chemical records were compared with meteorological conditions at the mesoscale and the synoptic-scale. Particular focus was given to an abrupt change in sea salt concentrations and δ18O within a depth range that appears from AWS accumulation data to have been deposited over a 24 hour period. The abrupt change in the firn core record was found to be consistent with an abrupt change in meteorological conditions. Direct comparisons between high resolution firn core records and meteorological conditions will greatly facilitate the interpretation of signals preserved in deep ice cores.
The effect of body size on metal accumulations in the bivalve Laternula elliptica
Authors: Ahn In-Young , Kang Jaekyoon , Kim Ko-Woon
Published: April 2004

Variations of metal concentrations with body size were investigated in kidney, digestive gland and gill of the Antarctic clam, Laternula elliptica, collected from a near-shore habitat at King George Island. Positive relationships for metal concentrations with body size were common among the three organs for most of the metals, while an inverse relationship was found only in the digestive gland for Cu, Zn and Mn. In the gill, concentrations of eight out of the ten metals increased linearly with body size, whilst in the kidney concentrations of Cd, Zn, Pb, Co and Ni were best fitted by quadratic regression curves, viz. increasing continuously until reaching a peak at around an 80 mm shell length. This may reflect specific regulatory activities for the extremely high accumulation of these metals in the kidney, particularly Cd (28–354 μg g−1 tissue dry weight). The overall prevalence of positive relationships indicate net accumulation of these metals throughout life, which may be at least in part associated with the slow growth and long life span of this cold-water bivalve species. The study demonstrates distinct body size-metal concentration relationships in the three organs of L. elliptica, and suggests they may be useful as biomonitors for assessing changes in metal concentrations in Antarctic waters.
Were the Larsemann Hills ice-free through the Last Glacial Maximum?
Authors: Hodgson D.A. , Noon P.E. , Vyverman W. , Bryant C.L. , Gore D.B. , Appleby P. , Gilmour M. , Verleyen E. , Sabbe K. , Jones V.J. , Ellis-Evans J.C. , Wood P.B.
Published: April 2004

Lake sediments in the Larsemann Hills contain a great diversity of biological and physical markers from which past environments can be inferred. In order to determine the timing of environmental changes it is essential to have accurate dating of sediments. We used radiometric (210Pb and 137Cs), radiocarbon (AMS 14C) and uranium series (238U) methods to date cores from eleven lakes. These were sampled on coastal to inland transects across the two main peninsulas, Broknes and Stornes, together with a single sample from the Bolingen Islands. Radiometric dating of recent sediments yielded 210Pb levels below acceptable detection limits. However, a relatively well-defined peak in 137Cs gave a date marker which corresponds to the fallout maximum from the atmospheric testing of atomic weapons in 1964/65. Radiocarbon (AMS 14C) measurements showed stratigraphical consistency in the age-depth sequences and undisturbed laminae in some cores provides evidence that the sediments have remained undisturbed by glacial action. In addition, freshwater surface sediments were found to be in near-equilibrium with modern 14CO2 and not influenced by radiocarbon contamination processes. This dating program, together with geomorphological records of ice flow directions and glacial sediments, indicates that parts of Broknes were ice-free throughout the Last Glacial Maximum and that some lakes have existed continuously since at least 44 ka bp. Attempts to date sediments older than 44 ka bp using 128U dating were inconclusive. However, supporting evidence for Broknes being ice-free is provided by an Optically Stimulated Luminescence date from a glaciofluvial deposit. In contrast, Stornes only became ice-free in the mid to late Holocene. This contrasting glacial history results from the Dålk Glacier which diverts ice around Broknes. Lakes on Broknes and some offshore islands therefore contain the oldest known lacustrine sediment records from eastern Antarctica, with the area providing an ice-free oasis and refuge for plants and animals throughout the Last Glacial Maximum. These sediments are therefore well placed to unravel a unique limnological sequence of environmental and climate changes in East Antarctica from the late Pleistocene to the present. This information may help better constrain models of current climate changes and ensure the adequate protection of these lakes and their catchments from the impacts of recent human occupation.
Tandem Benzyne Cycloadditions Leading to Polycyclic Compounds
Authors: Nogueira Encarna , Guitián Enrique , Castedo Luis , Castiñeiras Alfonso
Published: April 2004

Deoxykojic acid (1) reacts with two benzyne molecules to afford
9-methyl-7-phenoxy-5,9-dihydro-5,9-epoxy-6H-benzocyclohepten-6-one
(2) in 33% yield. Maltol (5) reacts with three molecules of benzyne to
afford
(4bα,5β,10β,11aα)-10-methyl-11a-phenoxy-4b,5,10,11a-tetrahydro-5,10-epoxy-11H-
benzo[a]benzo[3,4]cyclobuta[1,2-d]cyclohepten-11-one
(6a) in 36% yield.
PIKE-A is amplified in human cancers and prevents apoptosis by up-regulating Akt
Authors: Ahn Jee-Yin , Hu Yuanxin , Kroll Todd G. , Allard Paulette , Ye Keqiang
Published: April 2004

PIKE-A (PIKE-activating
A
kt), an isoform of PIKE GTPase that enhances phosphatidylinositol 3-kinase (PI3-kinase) activity, specifically binds to active Akt but not PI3-kinase. PIKE-A stimulates Akt activity in a GTP-dependent manner and promotes invasiveness of cancer cell lines. Here, we show that PIKE-A is amplified in a variety of human cancers and that amplified PIKE-A directly stimulates Akt and inhibits apoptosis compared to cells with normal PIKE-A copy number. Overexpression of PIKE-A wild-type but not dominant-negative mutant stimulates Akt activity and prevents apoptosis. Moreover, knockdown of PIKE-A diminishes Akt activity and increases apoptosis. Our findings suggest that PIKE-A amplification contributes to cancer cell survival and progression by inhibiting apoptosis through up-regulating Akt.
The cleft lip and palate defects inDancermutant mice result from gain of function of theTbx10gene
Authors: Bush Jeffrey O. , Lan Yu , Jiang Rulang
Published: April 2004

Cleft lip and palate (CL/P) is a common disfiguring birth defect with complex, poorly understood etiology. Mice carrying a spontaneous mutation,Dancer(Dc), exhibit CL/P in homozygotes and show significantly increased susceptibility to CL/P in heterozygotes [Deol, M. S. & Lane, P. W. (1966)J. Embryol. Exp. Morphol.16, 543–558 and Trasler, D. G., Kemp, D. & Trasler, T. A. (1984)Teratology29, 101–104], providing an animal model for understanding the molecular pathogenesis of CL/P. We genetically mappedDcto within a 1-cM region near the centromere of chromosome 19.In situhybridization analysis showed that one positional candidate gene,Tbx10, is ectopically expressed inDcmutant embryos. Positional cloning of theDclocus revealed an insertion of a 3.3-kb sequence containing the 5′ region of thep23gene into the first intron ofTbx10, which causes ectopic expression of ap23-Tbx10chimeric transcript encoding a protein product identical to a normal variant of the Tbx10 protein. Furthermore, we show that ectopic expression ofTbx10in transgenic mice recapitulates theDcmutant phenotype, indicating that CL/PinDcmutant mice results from thep23insertion-induced ectopicTbx10expression. These results identify gain of function of a T-box transcription factor gene as a mechanism underlying CL/P pathogenesis.
Multidimensional signatures in antimicrobial peptides
Authors: Yount Nannette Y. , Yeaman Michael R.
Published: April 2004

Conventional analyses distinguish between antimicrobial peptides by differences in amino acid sequence. Yet structural paradigms common to broader classes of these molecules have not been established. The current analyses examined the potential conservation of structural themes in antimicrobial peptides from evolutionarily diverse organisms. Using proteomics, an antimicrobial peptide signature was discovered to integrate stereospecific sequence patterns and a hallmark three-dimensional motif. This striking multidimensional signature is conserved among disulfide-containing antimicrobial peptides spanning biological kingdoms, and it transcends motifs previously limited to defined peptide subclasses. Experimental data validating this model enabled the identification of previously unrecognized antimicrobial activity in peptides of known identity. The multidimensional signature model provides a unifying structural theme in broad classes of antimicrobial peptides, will facilitate discovery of antimicrobial peptides as yet unknown, and offers insights into the evolution of molecular determinants in these and related host defense effector molecules.
Communication between the active sites and dimer interface of a herpesvirus protease revealed by a transition-state inhibitor
Authors: Marnett Alan B. , Nomura Anson M. , Shimba Nobuhisa , de Montellano Paul R. Ortiz , Craik Charles S.
Published: April 2004

Structurally diverse organophosphonate inhibitors targeting the active site of the enzyme were used to investigate the relationship of the active site and the dimer interface of wild-type protease in solution. Positional scanning synthetic combinatorial libraries revealed Kaposi's sarcoma-associated herpesvirus protease to be highly specific, even at sites distal to the peptide bond undergoing hydrolysis. Specificity results were used to synthesize a hexapeptide diphenylphosphonate inhibitor of Kaposi's sarcoma-associated herpesvirus protease. The transition state analog inhibitors covalently phosphonylate the active site serine, freezing the enzyme structure during catalysis. An NMR-based assay was developed to monitor the native monomer-dimer equilibrium in solution and was used to demonstrate the effect of protease inhibition on the quaternary structure of the enzyme. NMR, circular dichroism, and size exclusion chromatography analysis showed that active site inhibition strongly regulates the binding affinity of the monomer-dimer equilibrium at the spatially separate dimer interface of the protease, shifting the equilibrium to the dimeric form of the enzyme. Furthermore, inhibitor studies revealed that the catalytic cycles of the spatially separate active sites are independent. These results (
i
) provide direct evidence that peptide bond hydrolysis is integrally linked to the quaternary structure of the enzyme, (
ii
) establish a molecular mechanism of protease activation and stabilization during catalysis, and (
iii
) highlight potential implications of substoichiometric inhibition of the viral protease in developing herpesviral therapeutics.
ProteoMix: an integrated and flexible system for interactively analyzing large numbers of protein sequences
Authors: Chikayama Eisuke , Kurotani Atsushi , Kuroda Yutaka , Yokoyama Shigeyuki
Published: April 2004

Summary: ProteoMix is a suite of JAVA programs for identifying, annotating and predicting regions of interest in large sets of amino acid sequences, according to systematic and consistent criteria. It is based on two concepts (1) the integration of results from different sequence analysis tools increases the prediction reliability; and (2) the integration protocol is critical and needs to be easily adaptable in a case-by-case manner. ProteoMix was designed to analyze simultaneously multiple protein sequences using several bioinformatics tools, merge the results of the analyses using logical functions and display them on an integrated viewer. In addition, new sequences can be added seamlessly to an analysis performed on an initial set of sequences. ProteoMix has a modular design, and bioinformatics tools are run on remote servers accessed using the Internet Simple Object Access Protocol (SOAP), ensuring the swift implementation of additional tools. ProteoMix has a user-friendly interactive graphical user interface environment and runs on PCs with Microsoft OS.

Availability: ProteoMix is freely available for academic users at http://bio.gsc.riken.jp/ProteoMix/.
Evidence for secondary planktonic transport of post‐larvae of seagrass‐associated King George whiting
Authors: Moran S. M. , Jenkins G. P. , Keough M. J. , Hindell J. S.
Published: April 2004

Stomach contents and stable isotope analyses were used to determine if secondary planktonic dispersal of King George whiting Sillaginodes punctata post‐larvae from shallow inshore habitats in a large embayment in south‐eastern Australia was initiated by wave disturbance. Benthic harpacticoid copepods, which live in and amongst seagrass shoots, were found in the stomachs of S. punctata caught offshore in the plankton only during rough weather. Stable isotope analyses showed that the base of nutritional support, estimated from values of δ13C, of S. punctata collected in the plankton changed significantly during rough (waves > 0·25 m) compared to calm (waves < 0·25 m) weather conditions. Values of δ13C collected from S. punctata in the plankton during rough weather were more consistent with S. punctata values found in the seagrass. Sillaginodes punctata collected in the plankton and seagrass during rough and calm weather failed to show differences in δ15N values. Dietary and isotope analyses support a model whereby newly arrived S. punctata larvae can be resuspended from seagrass beds and dispersed offshore by wave action during onshore winds. Secondary planktonic dispersal in S. punctata would provide a mechanism by which seagrass beds further inside Port Phillip Bay are colonized.
Serum levels of testosterone, 11‐ketotestosterone and oestradiol‐17β in three species of sturgeon during gonadal development and final maturation induced by hormonal treatment
Authors: Barannikova I. A. , Bayunova L. V. , Semenkova T. B.
Published: April 2004

Changes in serum concentrations of two androgens, testosterone (T) and 11‐ketotestosterone (11KT), and oestradiol‐17β(E2) in male and female giant sturgeon Huso huso, Russian sturgeon Acipenser gueldenstaedtii and stellate sturgeon Acipenser stellatus were studied at different stages of gonadal maturity and after final maturation induced by hormonal treatment. Both male and female fish displayed a distinct increase in serum steroid concentrations during gonadal development. 11KT levels were significantly higher in males than females, with a positive correlation detected between 11KT and T concentrations. In maturing males and females, higher values of both 11KT and T were observed in stellate sturgeon compared to giant and Russian sturgeons. Vitellogenesis and high E2 levels were correlated in maturing sturgeon females.
Current performance of patient sample collection in the UK
Authors: Murphy M. F. , Stearn B. E. , Dzik W. H.
Published: April 2004

summary Collection of the patient sample for pretransfusion testing begins a complex chain of events in the transfusion process. Hospitals in England and North Wales were surveyed to compare local policies against recommendations of the British Committee for Standards in Haematology (BCSH). Hospitals also measured the frequency of rejected and miscollected samples [designated as wrong blood in tube (WBIT)]. 185 of 360 (51·4%) hospitals returned questionnaires and 182 of 185 (98%) hospitals reported that a policy for sample collection existed. Apart from frequent omission of the gender of the patient, there was 96% compliance with all mandatory identifiers of the BCSH guidelines. Practice allowing additions or changes to labelling on sample tubes and request forms varied. 3·2% (14 114/445 726) of samples submitted were rejected for various reasons, the most frequent being incomplete or missing information (49·5% of the total rejected samples). The corrected mean frequency for WBIT in the 27 hospitals with one or more observed WBIT was 1 in 1501 samples (95% CI: ≤1129·09 to ≤1872·91), and the median corrected frequency for WBIT was 1 in 1303 samples. This study has identified great variation in the policy and practice for sample collection for pretransfusion testing. Regular tracking of the rates of sample rejection and WBIT could be used to identify poor performance in individual hospitals requiring investigation and action.
Study of ochratoxin A‐producing strains in coffee processing
Authors: Suárez‐Quiroz Mirna , González‐Rios Oscar , Barel Michel , Guyot Bernard , Schorr‐Galindo Sabine , Guiraud Joseph‐Pierre
Published: April 2004

Ochratoxin A (OTA) is the main mycotoxin that has been detected in coffee. The occurrence of OTA in coffee beans can be because of environmental conditions and/or processing conditions. Three coffee processes were evaluated (wet, mechanical and dry processes), at different stages from harvesting to storage, and fungi producing OTA were enumerated and identified. The frequency of potential OTA‐producing fungi and their ability to produce OTA was also studied. By direct plating, the levels of contamination found in the coffee processes were 80, 72 and 92%, respectively, for parchment and dry cherry coffee and 20, 34 and 15% for green coffee. Aspergillus ochraceus isolated from the three processes accounted for 6.6, 8.3 and 3.3%, and Aspergillus niger for 15, 13 and 25% of the strains isolated, respectively. The toxigenic potential of five A. ochraceus and two A. niger strains was tested in FDA medium and coffee medium using the HPLC technique. There was no difference between the processes studied in terms of isolation and occurrence of ochratoxigenic fungi.
Race and the Incidence of Unemployment in South Africa
Authors: Kingdon Geeta Gandhi , Knight John
Published: April 2004

South Africa's unemployment rate is one of the highest in the world, and it has important distributional implications. The paper examines both entry into and duration of unemployment using data for the mid‐1990s. A probit model of unemployment shows an important role for race, education, age, gender, home‐ownership, location, and numerous other variables, all of which have plausible explanations. The large race gap in unemployment is explored further by means of a decomposition analysis akin to that normally used to analyze wage discrimination. There remains a substantial residual which might represent unobserved characteristics, such as quality of education, or discrimination.
A Reexamination of the Time Path of Wage Differentials in Taiwan
Authors: Lin Chun‐Hung A. , Orazem Peter F.
Published: April 2004

Contrary to the conclusions of a recent paper by Chen and Hsu (Review of Development Economics, vol. 5, 2001, pp. 336–54), wage inequality and returns to college‐educated workers have risen in Taiwan since 1980. Government policies which have caused rapid expansion of the supply of new college graduates have depressed returns for only the youngest cohorts of college graduates. Older cohorts of college graduates experienced rising returns, as have college graduates as a whole. Young college‐educated women's returns fell more and older college‐educated women's returns rose more relative to their male counterparts. Consequently, the rising share of women in the labor force helped amplify these trends. Changing trade patterns have tended to increase labor demand in sectors that use educated labor more intensively, helping to raise returns to skill. However, in contrast to western economies, rising capital intensity does not appear to have accelerated the pay gap by skill in Taiwan.