bluuebunny/crossref_metadata_2025_split huggingface dataset:
Living donor liver transplantation in patients with hepatitis C
Authors: Zimmerman Michael A. , Trotter James F. 
Published: October 2003

Key points
1. Hepatitis C virus (HCV) is the most common indication for living donor liver transplantation (LDLT).
2. Preliminary evidence suggests that HCV may occur earlier and may be more severe in LDLT recipients. However, current data is inconclusive relative to the impact of recurrent HCV on patient and graft survival in LDLT recipients.
3. Potential mechanisms for differences in severity of HCV in LDLT recipients are discussed.
4. LDLT remains a viable treatment option for selected patients with HCV.
The clinical and immunologic impact of using interferon and ribavirin in the immunosuppressed host
Authors: Braun Marius , Vierling John M. 
Published: October 2003

Key points
1. Allograft infection with hepatitis C virus (HCV) in immunosuppressed adults results in decreased allograft and patient survival.
2. Risk factors for accelerated progression of hepatitis C related to immunosuppression include treated episodes of acute cellular rejection (ACR), pulse therapy with methylprednisolone, and use of OKT3.
3. Both interferon alfa (IFN-α) and ribavirin (RVN) show antiviral actions against HCV and stimulate innate and adaptive immunity to increase cytolysis and polarize T helper subtype 1 (TH1) responses. In addition, IFN-α inhibits fibrogenesis in the liver.
4. Both IFN-α and RVN have been studied in immunosuppressed liver transplant recipients as prophylaxis or treatment of established hepatitis C to reduce allograft failure and patient mortality. Reported protocols include monotherapies with RVN, standard IFN-α, and pegylated IFN-α and combination therapies using RVN and either standard IFN-α or pegylated IFN-α.
5. The clinical impact of using IFN-α and RVN in highly selected immunosuppressed patients varied among studies. Combination therapy with standard IFN-α and RVN resulted in the greatest sustained biochemical and virological responses. However, no therapy prevented progression of acute cholestatic hepatitis C despite evidence of virological responses. Substantial proportions of patients developed adverse events requiring dose reduction or discontinuation that compromised efficacy. RVN monotherapy was not only virologically ineffective, but may have stimulated hepatic fibrosis. Current data regarding monotherapy or combination therapy with pegylated IFN-α are limited, but encouraging.
6. Despite potent immunostimulatory actions of both IFN-α and RVN that enhance natural killer, TH1, their use did not significantly increase the incidence of ACR.
7. Additional studies are needed to resolve the controversy over prophylaxis versus treatment of established disease and the potential utility of low-dose maintenance IFN-α therapy to retard fibrogenesis without clearing HCV.
8. After new, less toxic, and more potent antiviral agents become available, they should be tested immediately in patients with hepatitis C post-liver transplantation.
How can we identify better those with recurrent hepatitis C who will respond to therapy? What are the optimal treatment regimen and treatment duration?
Authors: Wright Teresa L. 
Published: October 2003

Key points
1. Treatment responses are lower in immune compromised patients such as those with hepatitis C virus (HCV) disease following liver transplantation than in immune competent patients with HCV disease.
2. Predictors of nonresponse, extrapolated from studies of immune competent patients, are overly represented in liver transplantation patients (high levels of HCV RNA and genotype 1 infection).
3. Tolerability of peginterferon plus ribavirin therapy is lower in transplant patients than in immune competent patients with HCV disease, in part because of a baseline renal insufficiency that increases the likelihood of ribavirin-associated anemia.
4. Clear recommendations regarding optimal treatment regimens for patients with posttransplantation HCV disease are problematic since there are few prospective, randomized, controlled trials that evaluated different treatment regimens.
5. If treatment is undertaken, baseline creatinine clearance should be measured and patients should be started on a dose of ribavirin of 400mg bid, or lower if renal function is impaired.
6. Tolerated peginterferon doses may be somewhat lower than for the standard immune competent patients. It is likely that lower doses will not greatly compromise response (1.0 ug/kg/week for peginterferon alfa 2b and 135 ug/week for peginterferon alfa 2a).
7. Optimal treatment duration is unknown. In patients with an on-treatment response, at least 12 months of therapy is recommended.
8. More potent drugs with fewer toxicities are needed for patients with progressive posttransplantation liver disease.
The UAB Proteomics Database
Authors: Hill Aubrey , Kim Helen 
Published: November 2003

Abstract
Summary: The University of Alabama at Birmingham (UAB) Proteomics Database (UPD) (http://www.uab.edu/proteinmenu) was created to provide a repository for the storage and linkage of two-dimensional (2D) gel images and the associated information obtained through mass spectrometry analysis of the proteins excised from the 2D gels in a manner similar to the SWISS-2DPAGE database and the Stanford Microarray Database. This was accomplished through the development of a web interface, a relational database, image maps and hyperlinks stored in the database. In addition to the internally generated data, UPD provides links to the National Center for Biotechnology Information via accession number hyperlinks. UPD currently contains information on 44 individual proteins derived from four experiments conducted by four UAB faculty members. Images of the gels from which each of these proteins was isolated are accessed by hyperlinks embedded in the database.
Availability: The UAB Proteomics Database can be accessed at http://www.uab.edu/proteinmenu
Markovian negentropies in bioinformatics. 1. A picture of footprints after the interaction of the HIV-1 Ψ-RNA packaging region with drugs
Authors: Díaz Humberto González , Ramos de Armas Ronal , Molina Reinaldo 
Published: November 2003

Abstract
Motivation: Many experts worldwide have highlighted the potential of RNA molecules as drug targets for the chemotherapeutic treatment of a range of diseases. In particular, the molecular pockets of RNA in the HIV-1 packaging region have been postulated as promising sites for antiviral action. The discovery of simpler methods to accurately represent drug–RNA interactions could therefore become an interesting and rapid way to generate models that are complementary to docking-based systems.
Results: The entropies of a vibrational Markov chain have been introduced here as physically meaningful descriptors for the local drug–nucleic acid complexes. A study of the interaction of the antibiotic Paromomycin with the packaging region of the RNA present in type-1 HIV has been carried out as an illustrative example of this approach. A linear discriminant function gave rise to excellent discrimination among 80.13% of interacting/non-interacting sites. More specifically, the model classified 36/45 nucleotides (80.0%) that interacted with paromomycin and, in addition, 85/106 (80.2%) footprinted (non-interacting) sites from the RNA viral sequence were recognized. The model showed a high Matthews’ regression coefficient (C = 0.64). The Jackknife method was also used to assess the stability and predictability of the model by leaving out adenines, C, G, or U. Matthews’ coefficients and overall accuracies for these approaches were between 0.55 and 0.68 and 75.8 and 82.7, respectively. On the other hand, a linear regression model predicted the local binding affinity constants between a specific nucleotide and the aforementioned antibiotic (R2 = 0.83,Q2 = 0.825). These kinds of models may play an important role either in the discovery of new anti-HIV compounds or in the elucidation of their mode of action.
Availability: On request from the corresponding author (humbertogd@cbq.uclv.edu.cu or humbertogd@navegalia.com)
Inhomogeneous molecular density: reference packing densities and distribution of cavities within proteins
Authors: Rother Kristian , Preissner Robert , Goede Andrean , Frömmel Cornelius 
Published: November 2003

Abstract
Motivation: There is no consensus in the literature about how the deepest portions of protein structures are packed. Using an improved Voronoi procedure, we calculate reference packing densities for different regions in the protein interior. Furthermore, we want to clarify where cavities are located.
Results: Sets of reference packing densities are provided for regions in proteins that differ in their distance to the surface and to internal cavities, supplementing previous data. Packing in the protein interior is tight but generally inhomogeneous. There are about 4.4 cavities per 100 amino acids in protein structures, they occur in all regions, most frequently in a depth of 2.5–3.6 Å underneath the Connolly surface. However, the deepest protein regions have a lower mean packing density than circumjacent regions, because more contacts to cavities occur in the core.
Availability/Supplementary information: Calculation software and detailed packing data are available on request.
RankViaContact: ranking and visualization of amino acid contacts
Authors: Shen Bairong , Vihinen Mauno 
Published: November 2003

Abstract
Summary: RankViaContact is a web service for calculation of residue–residue contact energies in proteins based on a coarse-grained model, and for visualization of interactions. The service provides information about ranked contact energies of residues, coordination numbers and the relative solvent accessibility of selected residues, as well as sequence and structure information. The program can be used to design stabilizing mutations, to analyze residue–residue contacts and to study the consequences of mutations.
Availability: http://bioinf.uta.fi/Rank.htm
A new sequence distance measure for phylogenetic tree construction
Authors: Otu Hasan H. , Sayood Khalid 
Published: November 2003

Abstract
Motivation: Most existing approaches for phylogenetic inference use multiple alignment of sequences and assume some sort of an evolutionary model. The multiple alignment strategy does not work for all types of data, e.g. whole genome phylogeny, and the evolutionary models may not always be correct. We propose a new sequence distance measure based on the relative information between the sequences using Lempel–Ziv complexity. The distance matrix thus obtained can be used to construct phylogenetic trees.
Results: The proposed approach does not require sequence alignment and is totally automatic. The algorithm has successfully constructed consistent phylogenies for real and simulated data sets.
Availability: Available on request from the authors.
Information Systems, Operational Research and Business Reengineering
Authors: Galliers R.D. 
Published: November 2003

There has been much concern expressed during recent times to ensure that information technology (IT) considerations are firmly aligned with business imperatives. For example, two of the top ranked information systems management issues during the 1980s were concerned with the problems incurred in aligning the Information Systems function with that of the organisation as a whole, and in linking information systems and business strategies.Conversely, recent research and practice has provided us with a vision of IT‐induced business process redesign, the opportunity for inter‐organisational systems and even the redefinition and refocusing of business products and services.The reality for many organisations remains that IT investment is seen as a necessary evil at best, with many questioning whether it represents value for money. There have also been somewhat negative reactions to the topic of business process redesign itself: is it old wine in a new bottle? And is it all too risky a business to suggest that radical change rather than incremental change is what is required?This paper reviews these issues and argues for a refocussing of our attention on (i) information and business systems, and (ii) implementation issues and organisational change, as opposed to the more common practice of concentrating on information technology per se. It takes an organisational, soft operational research perspective on the subject of business reengineering, and provides some outline guidelines for the process of managing the change that is often both necessary and potentially desirable with the introduction and utilisation of new IT. It raises the question whether the lessons from the application of the softer operational research approaches over the past 20 years or so could be used to provide a more informed intervention, given the complexity of the task... and answers that question in the affirmative!
From Voucher Auditing to Junkyard Dogs: The Evolution of Federal Inspectors General
Authors: Adair John J. , Simmons Rex 
Published: November 2003

Accountability in American government reaches as far back as the Continental Congress and General Washington's army. This tradition of accountability is carried on today by inspector general offices set up in almost every major department of the federal government. Through their audits and investigations, the inspectors general voice concerns over government internal controls, economy, efficiency, and effectiveness. Since 1981 they claim savings from their work totaling $92 billion.“Some officials handle large sums of public money; it is therefore necessary to have other officials to receive and examine the accounts. These inspectors must administer no funds themselves. Different cities call them examiners, auditors, scrutineers and public advocates.” These are the words of Aristotle in 325 B.C. Today, the United States government has its inspectors general to examine, audit, scrutinize, and advocate.
Identification and Characterization of a pSLA2 Plasmid Locus Required for Linear DNA Replication and Circular Plasmid Stable Inheritance in
Streptomyces lividans
Authors: Qin Zhongjun , Shen Meijuan , Cohen Stanley N. 
Published: November 2003

ABSTRACT

Streptomyces
linear plasmids and linear chromosomes can replicate also in a circular form when their telomeres are deleted. The 17-kb linear plasmid pSLA2 has been a useful model in studies of such replicons. Here we report that the minimal origin initiating replication of pSLA2-derived plasmids as circular molecules cannot propagate these plasmids in a linear mode unless they also contain a novel plasmid-encoded locus, here named
rlrA
(required for linear replication). In contrast with the need for
rlrA
to accomplish replication of telomere-containing linear plasmids, expression of
rlrA
, which encodes two LuxR family regulatory domains, interferes with the establishment of pSLA2 in circular form in
Streptomyces lividans
transformants. The additional presence of an adjacent divergently transcribed locus,
rorA
(rlrA override), which strongly resembles the
kor
(kil override) transcription control genes identified previously on
Streptomyces
plasmids, reversed the detrimental effects of
rlrA
on plasmid establishment and additionally stabilized circular plasmid inheritance by spores during the
S. lividans
life cycle. While the effects of the
rlrA/rorA
locus of pSLA2 were seen also on linear plasmids derived from the unrelated SLP2 replicon, they did not extend to plasmids whose replication was initiated at a cloned chromosomal origin. Our results establish the existence of, and provide the initial description of, a novel plasmid-borne regulatory system that differentially affects the propagation of linear and circular plasmids in
Streptomyces
.
Temperature Sensing by the
dsrA
Promoter
Authors: Repoila F. , Gottesman S. 
Published: November 2003

ABSTRACT

Synthesis of the small regulatory RNA DsrA is under temperature control. The minimal
dsrA
promoter of 36 bp contains sufficient information to ensure such regulation. In vivo, we have analyzed the critical elements responsible for the temperature control of
dsrA
by using a collection of chimeric promoters combining various elements of the
dsrA
promoter and the
lacUV5
promoter, which does not respond to temperature. Our results favor an RNA polymerase-DNA interaction model instead of a
trans
-acting factor for temperature regulation. While all of the elements of the
dsrA
promoter contribute to temperature-sensitive expression, the sequence of the −10 box and the spacer region are the essential elements for the thermal response of the
dsrA
promoter. The proper context for these promoter elements, including at least one of the flanking elements, the −35 region or the start site region, is also required. Point mutations demonstrate that the sequence of the −10 box imposes constraints on the length and the sequence of the spacer and/or its AT richness, even at low temperature. These results show a complex interdependence of different regions in the promoter for temperature regulation.
Slr2013 Is a Novel Protein Regulating Functional Assembly of Photosystem II in
Synechocystis
sp. Strain PCC 6803
Authors: Kufryk Galyna I. , Vermaas Wim F. J. 
Published: November 2003

ABSTRACT

The
Synechocystis
sp. strain PCC 6803, which has a T192H mutation in the D2 protein of photosystem II, is an obligate photoheterotroph due to the lack of assembled photosystem II complexes. A secondary mutant, Rg2, has been selected that retains the T192H mutation but is able to grow photoautotrophically. Restoration of photoautotrophic growth in this mutant was caused by early termination at position 294 in the Slr2013 protein. The T192H mutant with truncated Slr2013 forms fully functional photosystem II reaction centers that differ from wild-type reaction centers only by a 30% higher rate of charge recombination between the primary electron acceptor, Q
A
−
, and the donor side and by a reduced stability of the oxidized form of the redox-active Tyr residue, Y
D
, in the D2 protein. This suggests that the T192H mutation itself did not directly affect electron transfer components, but rather affected protein folding and/or stable assembly of photosystem II, and that Slr2013 is involved in the folding of the D2 protein and the assembly of photosystem II. Besides participation in photosystem II assembly, Slr2013 plays a critical role in the cell, because the corresponding gene cannot be deleted completely under conditions in which photosystem II is dispensable. Truncation of Slr2013 by itself does not affect photosynthetic activity of
Synechocystis
sp. strain PCC 6803. Slr2013 is annotated in CyanoBase as a hypothetical protein and shares a DUF58 family signature with other hypothetical proteins of unknown function. Genes for close homologues of Slr2013 are found in other cyanobacteria (
Nostoc punctiforme
,
Anabaena
sp. strain PCC 7120, and
Thermosynechococcus elongatus
BP-1), and apparent orthologs of this protein are found in
Eubacteria
and
Archaea
, but not in eukaryotes. We suggest that Slr2013 regulates functional assembly of photosystem II and has at least one other important function in the cell.
Virulence Conversion of
Legionella pneumophila
by Conjugal Transfer of Chromosomal DNA
Authors: Miyamoto Hiroshi , Yoshida Shin-ichi , Taniguchi Hatsumi , Shuman Howard A. 
Published: November 2003

ABSTRACT

In this study, we examined whether virulence conversion occurs in
Legionella pneumophila
by conjugal transfer of chromosomal DNA. A virulent strain, K6, which has the genes for Km
r
and LacZ
+
transposed in the chromosome of strain Philadelphia-1, which belongs to serogroup 1, was used as one parent, and an avirulent strain, Chicago-2S, which is a spontaneous streptomycin-resistant derivative of strain Chicago-2 belonging to serogroup 6, was used as the other parent. Experiments in which K6 (approximately 2.6 × 10
9
CFU) and Chicago-2S (approximately 8.9 × 10
9
CFU) were mated typically yielded 10
3
Km
r
Sm
r
LacZ
+
transconjugants. Thirty-two (about 2.8%) of 1,152 transconjugants belonging to serogroup 6 acquired the ability to grow intracellularly in
Acanthamoeba castellanii
and guinea pig macrophages. When guinea pigs were infected with sublethal doses of
Legionella
aerosols generated from one of these transconjugants (HM1011), they developed a severe pneumonia similar to that caused by donor strain K6. These results show that avirulent strain Chicago-2S changed into virulent strain HM1011 through conjugation with virulent strain K6. Furthermore, we showed that
Legionella
chromosomal virulence genes (
icm
-
dot
locus) were horizontally transferred by the conjugation system. The chromosomal conjugation system may play a role(s) in the evolution of
L
.
pneumophila
.
A Mutation in the Essential Gene
gmk
(Encoding Guanlyate Kinase) Generates a Requirement for Adenine at Low Temperature in
Salmonella enterica
Authors: Beck Brian J. , Huelsmeyer Mike , Paul Scott , Downs D. M. 
Published: November 2003

ABSTRACT

In
Salmonella enterica
serovar Typhimurium,
gmk
encodes guanylate kinase, an essential enzyme involved in the synthesis and salvage of guanine nucleotides. Here we report the isolation of a mutation in
gmk
that results in a nutritional requirement for adenine at low temperature. Comparisons of kinetic parameters from the wild-type and mutant Gmk enzymes revealed that the mutant enzyme had a more than 20-fold-higher

K
m

for ATP than the wild-type enzyme. The growth dependence of the mutant on temperature and/or adenine could not be explained as a direct result of this kinetic difference. We propose a model in which previously described regulatory effects of GMP are responsible for these phenotypes.
What do chronic obstructive pulmonary disease patients die from? Amultiple cause coding analysis
Authors: Hansell A.L. , Walk J.A. , Soriano J.B. 
Published: October 2003

Information on obstructive lung disease (OLD) deaths is generally derived from the underlying cause of death on the death certificate. This neglects information on other conditions mentioned and may underestimate the burden of disease.Descriptive analyses of all conditions mentioned on the death certificate for all decedents where OLD (chronic obstructive pulmonary disease or asthma) was mentioned as a contributing cause of death were conducted for England and Wales for 1993–1999.OLD was mentioned in 312,664 or 8.0% of all deaths. OLD comprised the underlying cause of death in 59.8% of deaths with any mention of OLD. Where OLD was not the underlying cause of death, the leading causes by the International Classification of Disease version 9 chapter were diseases of the circulatory system, neoplasms, and non-OLD diseases of the respiratory system. The top single causes were acute myocardial infarction, other ischaemic heart disease, and lung cancer.The current analysis confirms that using the underlying cause of death underestimates the contribution of obstructive lung disease to mortality in England and Wales, in contrast to myocardial infarction where underlying cause of death captures most (94%) mentions on the death certificate.