bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural aspects and biological properties of the cathelicidin PMAP‐36
Authors: Scocchi Marco , Zelezetsky Igor , Benincasa Monica , Gennaro Renato , Mazzoli Andrea , Tossi Alessandro
Published: August 2005

PMAP‐36 is a cathelicidin‐derived host defence peptide originally deduced by a transcript from pig bone marrow RNA. The expression of the propeptide in leukocytes, and the structure, antimicrobial activity, and mechanism of action of the mature peptide were investigated. The proform is stored as a dimeric precursor of 38 kDa formed by a dimerization site at its C‐terminal cysteine residue; it is likely that the mature peptide is dimeric when released. Monomeric and dimeric forms of PMAP‐36 were chemically synthesized and their activity compared. Both forms assumed an amphipathic α‐helical conformation and exhibited a potent and rapid microbicidal activity against a wide spectrum of microorganisms, mediated by their ability to permeabilize the microbial membranes rapidly. A shortened fragment localized the helical region to the N terminus, but showed a significantly lower potency and slower permeabilization kinetics, indicating an important role of the nonhelical C‐terminal hydrophobic portion of this molecule. Dimerization modulated the effectiveness of the peptide in terms of killing and permeabilization kinetics, and reduced medium dependence. It allows the molecule to achieve an impressive charge density (+28 in 70 residues), although the significance of this feature with respect to biological activity has yet to be determined.
Molecular cloning, recombinant expression and IgE‐binding epitope of ω‐5 gliadin, a major allergen in wheat‐dependent exercise‐induced anaphylaxis
Authors: Matsuo Hiroaki , Kohno Kunie , Morita Eishin
Published: August 2005

Wheatω‐5 gliadin has been identified as a major allergen in wheat‐dependent exercise‐induced anaphylaxis. We have detected seven IgE‐binding epitopes in primary sequence of the protein. We newly identified four additional IgE‐binding epitope sequences, QQFHQQQ, QSPEQQQ, YQQYPQQ and QQPPQQ, in three patients with wheat‐dependent exercise‐induced anaphylaxis in this study. Diagnosis and therapy of food allergy would benefit from the availability of defined recombinant allergens. However, because ω‐5 gliadin gene has not been cloned, recombinant protein is currently unavailable. We sought to clone the ω‐5 gliadin gene and produce the homogeneous recombinant protein for use in an in vitro diagnostic tool. Using a PCR‐based strategy we isolated two full‐length ω‐5 gliadin genes, designated ω‐5 and ω‐5b, from wheat genomic DNA and determined the nucleotide sequences. The protein encoded by ω‐5a was predicted to be 439 amino acids long with a calculated mass of 53 kDa; the ω‐5b gene would encode a 393 amino acid, but it contains two stop codons indicating that ω‐5b is pseudogene. The C‐terminal half (178 amino acids) of the ω‐5a gliadin protein, including all 11 IgE‐binding epitope sequences, was expressed in Escherichia coli by means of the pET system and purified using RP‐HPLC. Western blot analysis and dot blot inhibition assay of recombinant and native ω‐5 gliadin purified from wheat flour demonstrated that recombinant protein had IgE‐binding ability. Our results suggest that the recombinant protein can be a useful tool for identifying patients with wheat‐dependent exercise‐induced anaphylaxis in vitro.
Nop53p, an essential nucleolar protein that interacts with Nop17p and Nip7p, is required for pre‐rRNA processing in Saccharomyces cerevisiae
Authors: Granato Daniela C. , Gonzales Fernando A. , Luz Juliana S. , Cassiola Flávia , Machado‐Santelli Glaucia M. , Oliveira Carla C.
Published: August 2005

In eukaryotes, pre‐rRNA processing depends on a large number of nonribosomal trans‐acting factors that form large and intriguingly organized complexes. A novel nucleolar protein, Nop53p, was isolated by using Nop17p as bait in the yeast two‐hybrid system. Nop53p also interacts with a second nucleolar protein, Nip7p. A carbon source‐conditional strain with the NOP53 coding sequence under the control of the GAL1 promoter did not grow in glucose‐containing medium, showing the phenotype of an essential gene. Under nonpermissive conditions, the conditional mutant strain showed rRNA biosynthesis defects, leading to an accumulation of the 27S and 7S pre‐rRNAs and depletion of the mature 25S and 5.8S mature rRNAs. Nop53p did not interact with any of the exosome subunits in the yeast two‐hybrid system, but its depletion affects the exosome function. In pull‐down assays, protein A‐tagged Nop53p coprecipitated the 27S and 7S pre‐rRNAs, and His–Nop53p also bound directly 5.8S rRNA in vitro, which is consistent with a role for Nop53p in pre‐rRNA processing.
Comparative studies on the functional roles of N‐ and C‐terminal regions of molluskan and vertebrate troponin‐I
Authors: Tanaka Hiroyuki , Takeya Yuhei , Doi Teppei , Yumoto Fumiaki , Tanokura Masaru , Ohtsuki Iwao , Nishita Kiyoyoshi , Ojima Takao
Published: August 2005

Vertebrate troponin regulates muscle contraction through alternative binding of the C‐terminal region of the inhibitory subunit, troponin‐I (TnI), to actin or troponin‐C (TnC) in a Ca2+‐dependent manner. To elucidate the molecular mechanisms of this regulation by molluskan troponin, we compared the functional properties of the recombinant fragments of Akazara scallop TnI and rabbit fast skeletal TnI. The C‐terminal fragment of Akazara scallop TnI (ATnI232−292), which contains the inhibitory region (residues 104–115 of rabbit TnI) and the regulatory TnC‐binding site (residues 116–131), bound actin‐tropomyosin and inhibited actomyosin‐tropomyosin Mg‐ATPase. However, it did not interact with TnC, even in the presence of Ca2+. These results indicated that the mechanism involved in the alternative binding of this region was not observed in molluskan troponin. On the other hand, ATnI130−252, which contains the structural TnC‐binding site (residues 1–30 of rabbit TnI) and the inhibitory region, bound strongly to both actin and TnC. Moreover, the ternary complex consisting of this fragment, troponin‐T, and TnC activated the ATPase in a Ca2+‐dependent manner almost as effectively as intact Akazara scallop troponin. Therefore, Akazara scallop troponin regulates the contraction through the activating mechanisms that involve the region spanning from the structural TnC‐binding site to the inhibitory region of TnI. Together with the observation that corresponding rabbit TnI‐fragment (RTnI1−116) shows similar activating effects, these findings suggest the importance of the TnI N‐terminal region not only for maintaining the structural integrity of troponin complex but also for Ca2+‐dependent activation.
Specific degradation of H. pylori urease by a catalytic antibody light chain
Authors: Hifumi Emi , Hatiuchi Kenji , Okuda Takuro , Nishizono Akira , Okamura Yoshiko , Uda Taizo
Published: August 2005

Catalytic antibodies capable of digesting crucial proteins of pathogenic bacteria have long been sought for potential therapeutic use. Helicobacter pylori urease plays a crucial role for the survival of this bacterium in the highly acidic conditions of human stomach. The HpU‐9 monoclonal antibody (mAb) raised against H. pylori urease recognized the α‐subunit of the urease, but only slightly recognized the β‐subunit. However, when isolated both the light and the heavy chains of this antibody were mostly bound to the β‐subunit. The cleavage reaction catalyzed by HpU‐9 light chain (HpU‐9‐L) followed the Michaelis‐Menten equation with a Km of 1.6 × 10−5 m and a kcat of 0.11 min−1, suggesting that the cleavage reaction was enzymatic. In a cleavage test using H. pylori urease, HpU‐9‐L efficiently cleaved the β‐subunit but not the α‐subunit, indicating that the degradation by HpU‐9‐L had a specificity. The cleaved peptide bonds in the β‐subunit were L121‐A122, E124‐G125, S229‐A230, Y241‐D242, and M262‐A263. BSA was hardly cleaved by HpU‐9‐L, again indicating the digestion by HpU‐9‐L was specific. In summary, we succeeded in the preparation of a catalytic antibody light chain capable of specifically digesting the β‐subunit of H. pylori urease.
Utility of epimerization domains for the redesign of nonribosomal peptide synthetases
Authors: Stein Daniel B. , Linne Uwe , Marahiel Mohamed A.
Published: August 2005

Many pharmacologically important agents are assembled on multimodular nonribosomal peptide synthetases (NRPSs) whose modules comprise a set of core domains with all essential catalytic functions necessary for the incorporation and modification of one building block. Very often, d‐amino acids are found in such products which, with few exceptions, are generated by the action of NRPS integrated epimerization (E) domains that alter the stereochemistry of the corresponding peptidyl carrier protein (PCP) bound l‐intermediate. In this study we present a quantitative investigation of substrate specificity of four different E domains (two ‘peptidyl‐’ and two ‘aminoacyl‐’E domains) derived from different NRPSs towards PCP bound peptides. The respective PCP‐E bidomain apo‐proteins (TycB3‐, FenD2‐, TycA‐ and GrsA‐PCP‐E) were primed with various peptidyl‐CoA precursors by utilizing the promiscuous phosphopantetheinyl transferase Sfp. PCP bound peptidyl‐S‐Ppant epimerization products were chemically cleaved and analyzed for their l/d‐ratios by LCMS. We were able to show that all four E domains tolerate a broad variety of peptidyl‐S‐Ppant‐substrates as evaluated by kobs values and final l/d‐product equilibria determined for each reaction. The two C‐terminal amino acids of the substrate seem to be recognized by ‘peptidyl‐’E domains. Interestingly, the ‘aminoacyl‐’E domains GrsA‐ and TycA‐E were also able to convert the elongated intermediates. All four E domains accepted an N‐methylated precursor as well and epimerized this substrate with high efficiency. Finally, we could demonstrate that the condensation (C) domain of TycB1 is also able to process peptidyl substrates transferred by TycA. In conclusion, these findings are of great impact on future engineering attempts.
Protein glycation in Saccharomyces cerevisiae
Authors: Gomes Ricardo A. , Sousa Silva Marta , Vicente Miranda Hugo , Ferreira António E. N. , Cordeiro Carlos A. A. , Freire Ana Ponces
Published: August 2005

Methylglyoxal is the most important intracellular glycation agent, formed nonenzymatically from triose phosphates during glycolysis in eukaryotic cells. Methylglyoxal‐derived advanced glycation end‐products are involved in neurodegenerative disorders (Alzheimer's, Parkinson's and familial amyloidotic polyneurophathy) and in the clinical complications of diabetes. Research models for investigating protein glycation and its relationship to methylglyoxal metabolism are required to understand this process, its implications in cell biochemistry and their role in human diseases. We investigated methylglyoxal metabolism and protein glycation in Saccharomyces cerevisiae. Using a specific antibody against argpyrimidine, a marker of protein glycation by methylglyoxal, we found that yeast cells growing on d‐glucose (100 mm) present several glycated proteins at the stationary phase of growth. Intracellular methylglyoxal concentration, determined by a specific HPLC based assay, is directly related to argpyrimidine formation. Moreover, exposing nongrowing yeast cells to a higher d‐glucose concentration (250 mm) increases methylglyoxal formation rate and argpyrimidine modified proteins appear within 1 h. A kinetic model of methylglyoxal metabolism in yeast, comprising its nonenzymatic formation and enzymatic catabolism by the glutathione dependent glyoxalase pathway and aldose reductase, was used to probe the role of each system parameter on methylglyoxal steady‐state concentration. Sensitivity analysis of methylglyoxal metabolism and studies with gene deletion mutant yeast strains showed that the glyoxalase pathway and aldose reductase are equally important for preventing protein glycation in Saccharomyces cerevisiae.
Kinetic basis for linking the first two enzymes of chlorophyll biosynthesis
Authors: Shepherd Mark , McLean Samantha , Hunter C. Neil
Published: August 2005

Purified recombinant proteins from Synechocystis PCC6803 were used to show that the magnesium chelatase ChlH subunit stimulates magnesium protoporphyrin methyltransferase (ChlM) activity. Steady‐state kinetics demonstrate that ChlH does not significantly alter the Km for the tetrapyrrole substrate. However, quenched‐flow analysis reveals that ChlH dramatically accelerates the formation and breakdown of an intermediate in the catalytic cycle of ChlM. In light of the profound effect that ChlH has on the methyltransferase catalytic intermediate, the pre steady‐state analysis in the current study suggests that ChlH is directly involved in the reaction chemistry. The kinetic coupling between the chelatase and methyltransferase has important implications for regulation of chlorophyll biosynthesis and for the availability of magnesium protoporphyrin for plastid‐to‐nucleus signalling.
Insights into the interaction of human arginase II with substrate and manganese ions by site‐directed mutagenesis and kinetic studies
Authors: López Vasthi , Alarcón Ricardo , Orellana María S. , Enríquez Paula , Uribe Elena , Martínez José , Carvajal Nelson
Published: August 2005

To examine the interaction of human arginase II (EC 3.5.3.1) with substrate and manganese ions, the His120Asn, His145Asn and Asn149Asp mutations were introduced separately. About 53% and 95% of wild‐type arginase activity were expressed by fully manganese activated species of the His120Asn and His145Asn variants, respectively. The Km for arginine (1.4–1.6 mm) was not altered and the wild‐type and mutant enzymes were essentially inactive on agmatine. In contrast, the Asn149Asp mutant expressed almost undetectable activity on arginine, but significant activity on agmatine. The agmatinase activity of Asn149Asp (Km = 2.5 ± 0.2 mm) was markedly resistant to inhibition by arginine. After dialysis against EDTA, the His120Asn variant was totally inactive in the absence of added Mn2+ and contained < 0.1 Mn2+·subunit−1, whereas wild‐type and His145Asn enzymes were half active and contained 1.1 ± 0.1 Mn2+·subunit−1 and 1.3 ± 0.1 Mn2+·subunit−1, respectively. Manganese reactivation of metal‐free to half active species followed hyperbolic kinetics with Kd of 1.8 ± 0.2 × 10−8 m for the wild‐type and His145Asn enzymes and 16.2 ± 0.5 × 10−8 m for the His120Asn variant. Upon mutation, the chromatographic behavior, tryptophan fluorescence properties (λmax = 338–339 nm) and sensitivity to thermal inactivation were not altered. The Asn149→Asp mutation is proposed to generate a conformational change responsible for the altered substrate specificity of arginase II. We also conclude that, in contrast with arginase I, Mn2+A is the more tightly bound metal ion in arginase II.
Two novel variants of human medium chain acyl‐CoA dehydrogenase (MCAD)
Authors: O'Reilly Linda P. , Andresen Brage S. , Engel Paul C.
Published: August 2005

Two novel rare mutations, MCAD∼842G→C (R256T) and MCAD∼1166A→G (K364R), have been investigated to assess how far the biochemical properties of the mutant proteins correlate with the clinical phenotype of medium chain acyl‐CoA dehydrogenase (MCAD) deficiency. When the gene for K364R was overexpressed in Escherichia coli, the synthesized mutant protein only exhibited activity when the gene for chaperonin GroELS was co‐overexpressed. Levels of activity correlated with the amounts of native MCAD protein visible in western blots. The R256T mutant, by contrast, displayed no activity either with or without chaperonin, but in this case a strong MCAD protein band was seen in the western blots throughout. The proteins were also purified, and the enzyme function and thermostability investigated. The K364R protein showed only moderate kinetic impairment, whereas the R256T protein was again totally inactive. Neither mutant showed marked depletion of FAD. The pure K364R protein was considerably less thermostable than wild‐type MCAD. Western blots indicated that, although the R256T mutant protein is less thermostable than normal MCAD, it is much more stable than K364R. Though clinically asymptomatic thus far, both mutations have a severe impact on the biochemical phenotype of the protein. K364R, like several previously described MCAD mutant proteins, appears to be defective in folding. R256T, by contrast, is a well‐folded protein that is nevertheless devoid of catalytic activity. How the mutations specifically affect the catalytic activity and the folding is further discussed.
Probing the epoch of early baryonic infall through 21-cm fluctuations
Authors: Barkana R. , Loeb A.
Published: August 2005

After cosmological recombination, the primordial hydrogen gas decoupled from the cosmic microwave background (CMB) and fell into the gravitational potential wells of the dark matter. The neutral hydrogen imprinted acoustic oscillations on the pattern of brightness fluctuations due to its redshifted 21-cm absorption of the CMB. Unlike CMB temperature fluctuations which probe the power spectrum at cosmic recombination, we show that observations of the 21-cm fluctuations at z∼ 20–200 can measure four separate fluctuation modes (with a fifth mode requiring very high precision), thus providing a unique probe of the geometry and composition of the universe.
The extremely asymmetric radio structure of the z = 3.1 radio galaxy B3 J2330 + 3927
Authors: Pérez-Torres M.-A. , De Breuck C.
Published: August 2005

We report on 1.7- and 5.0-GHz observations of the z= 3.087 radio galaxy B3 J2330 + 3927, using the Very Long Baseline Array (VLBA), and archival 1.4- and 8.4-GHz Very Large Array (VLA) data. Our VLBA data identify a compact, flat-spectrum (α5 GHz1.7 GHz=−0.2 ± 0.1; Sν∝να) radio component as the core. The VLA images show that the fraction of core emission is very large (fc≈ 0.5 at 8.4 GHz), and reveal a previously undetected, very faint counterjet, implying a radio lobe flux density ratio R≳ 11 and a radio lobe distance ratio Q≈ 1.9. Those values are much more common in quasars than in radio galaxies, but the optical/near-infrared spectra show a clear type II active galactic nucleus for B3 J2330 + 3927, confirming that it is indeed a radio galaxy. Unlike all other radio galaxies, the bright Lyα-emitting gas is located towards the furthest radio arm. We argue against environmental and relativistic beaming effects being the cause of the observed asymmetry, and suggest this source has intrinsically asymmetric radio jets. If this is the case, B3 J2330 + 3927 is the first example of such a source at high redshift, and seems to be difficult to reconcile with the unified model, which explains the differences between quasars and radio galaxies as being due to orientation effects.
Firing up the nature/nurture controversy: bioethics and genetic determinism
Authors: de Melo-Martín I
Published: August 2005

It is argued here that bioethicists might inadvertently be promoting genetic determinism: the idea that genes alone determine human traits and behaviours. Discussions about genetic testing are used to exemplify how they might be doing so. Quite often bioethicists use clinical cases to support particular moral obligations or rights as if these cases were representative of the kind of information we can acquire about human diseases through genetic testing, when they are not. On other occasions, the clinical cases are presented in simplistic ways that portray genetic testing as yielding information more accurate than it actually is. It is concluded that, because of the problematic implications that the ideology of genetic determinism might have for individuals’ wellbeing and for our public policies, bioethicists should be careful to present these issues in ways that do not promote questionable ideas about the causal role of genes in human diseases and behaviours.
Paying research participants: a study of current practices in Australia
Authors: Fry C L , Ritter A , Baldwin S , Bowen K J , Gardiner P , Holt T , Jenkinson R , Johnston J
Published: August 2005

Objective:To examine current research payment practices and to inform development of clearer guidelines for researchers and ethics committees.

Design:Exploratory email based questionnaire study of current research participant reimbursement practices. A diverse sample of organisations and individuals were targeted.

Setting:Australia.

Participants:Contacts in 84 key research organisations and select electronic listservers across Australia. A total of 100 completed questionnaires were received with representations from a variety of research areas (for example, market, alcohol and drug, medical, pharmaceutical and social research).

Main measurements:Open-ended and fixed alternative questions about type of research agency; type of research; type of population under study; whether payment is standard; amounts and mechanisms of payment; factors taken into account when deciding on payment practices; and whether payment policies exist.

Results:Reimbursement practice is highly variable. Where it occurs (most commonly for drug dependent rather than health professional or general population samples) it is largely monetary and is for time and out-of-pocket expenses. Ethics committees were reported to be often involved in decision making around reimbursement.

Conclusions:Research subject payment practices vary in Australia. Researchers who do provide payments to research participants generally do so without written policy and procedures. Ethics committees have an important role in developing guidelines in this area. Specific guidelines are needed considering existing local policies and procedures; payment models and their application in diverse settings; case study examples of types and levels of reimbursement; applied definitions of incentive and inducement; and the rationale for diverse payment practices in different settings.
Medical learning curves and the Kantian ideal
Authors: Le Morvan P , Stock B
Published: August 2005

A hitherto unexamined problem for the “Kantian ideal” that one should always treat patients as ends in themselves, and never only as a means to other ends, is explored in this paper. The problem consists of a prima facie conflict between this Kantian ideal and the reality of medical practice. This conflict arises because, at least presently, medical practitioners can only acquire certain skills and abilities by practising on live, human patients, and given the inevitability and ubiquity of learning curves, this learning requires some patients to be treated only as a means to this end. A number of ways of attempting to establish the compatibility of the Kantian Ideal with the reality of medical practice are considered. Each attempt is found to be unsuccessful. Accordingly, until a way is found to reconcile them, we conclude that the Kantian ideal is inconsistent with the reality of medical practice.
Implant ethics: Table 1
Authors: Hansson S O
Published: August 2005

Implant ethics is defined here as the study of ethical aspects of the lasting introduction of technological devices into the human body. Whereas technological implants relieve us of some of the ethical problems connected with transplantation, other difficulties arise that are in need of careful analysis. A systematic approach to implant ethics is proposed. The major specific problems are identified as those concerning end of life issues (turning off devices), enhancement of human capabilities beyond normal levels, mental changes and personal identity, and cultural effects.
Balancing confidentiality and the information provided to families of patients in primary care
Authors: Pérez-Cárceles M D , Pereñiguez J E , Osuna E , Luna A
Published: August 2005

Background:Medical confidentiality underpins the doctor–patient relationship and ensures privacy so that intimate information can be exchanged to improve, preserve, and protect the health of the patient. The right to information applies to the patient alone, and, only if expressly desired, can it be extended to family members. However, it must be remembered that one of the primary tenets of family medicine is precisely that patient care occurs ideally within the context of the family. There may be, then, certain occasions when difficulties will arise as to the extent of the information provided to family members.

Objectives:This study aimed to describe family doctors’ attitudes to confidentiality and providing patient information to relatives as well as their justifications for sharing information.

Method:A descriptive postal questionnaire was self-administered by family doctors.

Results:Of 227 doctors, 95.1% provided information to a patient’s family and over a third (35%) disclosed information to others without prior patient consent.

Conclusions:The findings reveal that family doctors should pay more attention to their patients’ rights to information, privacy, and confidentiality, and reflect very carefully on the fine balance between this and the occasional need for the support and collaboration of family members in delivery of care. Emphasis should be placed on ethics and legal problems during undergraduate education and in-service training of doctors.
The new Italian law on assisted reproduction technology (Law 40/2004)
Authors: Fineschi V , Neri M , Turillazzi E
Published: August 2005

The Italian parliament passed the law on assisted reproduction after a heated debate. The promulgation of this law (Law 40/2004) is the end point of a long and troubled journey that has seen many bills come and go, all of which have failed. The law consists of a whole set of regulations that will have a great impact on health and on society in general. The law is against many of the technical practices of assisted reproduction; several such practices are banned. This paper outlines ethical and medicolegal issues arising in connection with the law. The law states that no more than three embryos must be created at any one time and all the embryos created must be transferred together even if the couple does not need all the embryos. Embryo cryopreservation is also forbidden, as is assisted reproductive technology (ART), which uses a third party in any way, and the screening of embryos for genetic defects.
A qualitative study of women’s views on medical confidentiality
Authors: Jenkins G , Merz J F , Sankar P
Published: August 2005

Context:The need to reinvigorate medical confidentiality protections is recognised as an important objective in building patient trust necessary for successful health outcomes. Little is known about patient understanding and expectations from medical confidentiality.

Objective:To identify and describe patient views of medical confidentiality and to assess provisionally the range of these views.

Design:Qualitative study using indepth, open ended face-to-face interviews.

Setting:Southeastern Pennsylvania and southern New Jersey, USA.

Participants:A total of 85 women interviewed at two clinical sites and three community/research centres.

Main outcome measures:Subjects’ understanding of medical confidentiality, beliefs about the handling of confidential information and concerns influencing disclosure of information to doctors.

Results:The subjects defined medical confidentiality as the expectation that something done or said would be kept “private” but differed on what information was confidential and the basis and methods for protecting information. Some considered all medical information as confidential and thought confidentiality protections functioned to limit its circulation to medical uses and reimbursement needs. Others defined only sensitive or potentially stigmatising information as confidential. Many of these also defined medical confidentiality as a strict limit prohibiting information release, although some noted that specific permission or urgent need could override this limit.

Conclusions:Patients share a basic understanding of confidentiality as protection of information, but some might have expectations that are likely not met by current practice nor anticipated by doctors. Doctors should recognise that patients might have their own medical confidentiality models. They should address divergences from current practice and provide support to those who face emotional or practical obstacles to self-revelation.
The White Bull effect: abusive coauthorship and publication parasitism
Authors: Kwok L S
Published: August 2005

Junior researchers can be abused and bullied by unscrupulous senior collaborators. This article describes the profile of a type of serial abuser, the White Bull, who uses his academic seniority to distort authorship credit and who disguises his parasitism with carefully premeditated deception. Further research into the personality traits of such perpetrators is warranted.
Project Examining Effectiveness in Clinical Ethics (PEECE): phase 1—descriptive analysis of nine clinical ethics services
Authors: Godkin M D , Faith K , Upshur R E G , MacRae S K , Tracy C S
Published: August 2005

Objective:The field of clinical ethics is relatively new and expanding. Best practices in clinical ethics against which one can benchmark performance have not been clearly articulated. The first step in developing benchmarks of clinical ethics services is to identify and understand current practices.

Design and setting:Using a retrospective case study approach, the structure, activities, and resources of nine clinical ethics services in a large metropolitan centre are described, compared, and contrasted.

Results:The data yielded a unique and detailed account of the nature and scope of clinical ethics services across a spectrum of facilities. General themes emerged in four areas—variability, visibility, accountability, and complexity. There was a high degree of variability in the structures, activities, and resources across the clinical ethics services. Increasing visibility was identified as a significant challenge within organisations and externally. Although each service had a formal system for maintaining accountability and measuring performance, differences in the type, frequency, and content of reporting impacted service delivery. One of the most salient findings was the complexity inherent in the provision of clinical ethics services, which requires of clinical ethicists a broad and varied skill set and knowledge base. Benchmarks including the average number of consults/ethicist per year and the hospital beds/ethicist ratio are presented.

Conclusion:The findings will be of interest to clinical ethicists locally, nationally, and internationally as they provide a preliminary framework from which further benchmarking measures and best practices in clinical ethics can be identified, developed, and evaluated.
Controversial choice of a control intervention in a trial of ventilator therapy in ARDS: standard of care arguments in a randomised controlled trial
Authors: Mann H
Published: August 2005

When evaluating an innovative intervention in a randomised controlled trial (RCT), choosing an appropriate control intervention is necessary for a clinically meaningful result. An RCT reported in 2000 addressed the relative merits of two tidal volume ventilatory strategies, 6 ml/kg (innovative) and 12 ml/kg (control), in patients with acute respiratory distress syndrome. Critics claim that the 12 ml/kg volume did not represent the clinical practice standard at that time, and that lower tidal volumes had been used in some patients prior to randomisation. The trialists responded that current practice involved the use of a broad range of tidal volumes, including 12 ml/kg. Appropriate control interventions for RCTs can be ensured by: a systematic review of the relevant literature; a formal survey of expert clinicians; and publication of the proposed research protocol to solicit critical appraisal. A global survey of experts during the RCT’s design stage would have been of probative value in determining the appropriate control tidal volume. Hypothetical, but plausible, results of such a survey are presented and examined to demonstrate the value of this method.
THE TECHNIQUE OF BUSINESS MODEL DRIVEN ANALYSIS AND TEST DESIGN FOR DEVELOPMENT OF WEB APPLICATIONS
Authors: CHO YONGSUN , LEE WOOJIN , CHONG KIWON
Published: August 2005

A technique for creating analysis models of a web application from a business model is proposed for easy and effective development. Moreover, a technique for generating test cases from the sequence diagrams for a web application is proposed. The use case diagram and web page list are generated from the business model which is depicted using the notations of the UML (Unified Modeling Language) activity diagram. The page diagram and logical/physical database models are created based on the web page list and extracted data fields. Test cases for the web application are generated from call messages (including self-call messages) of the UML sequence diagram. The effectiveness of these techniques is shown using a practical case study which is a development project of a web application for RMS (Research material Management System).
ARIFS METHODOLOGY: REUSING INCOMPLETE MODELS AT THE REQUIREMENTS SPECIFICATION STAGE
Authors: DÍAZ REDONDO REBECA P. , PAZOS ARIAS JOSÉ J. , FERNÁNDEZ VILAS ANA , GARCÍA DUQUE JORGE , GIL SOLLA ALBERTO
Published: August 2005

In a totally formalized, iterative and incremental software process, each iteration usually implies identifying new requirements, adding them to the current model of the system, checking again the consistency and, in many cases, modifying the model to satisfy all the functional requirements. In this context, the ARIFS (Approximate Retrieval of Incomplete and Formal Specifications) methodology provides a suitable reuse environment (1) to classify, retrieve and adapt formal and incomplete requirements specifications and (2) to reuse the formal verification results linked to them. In this paper, we focus on the first goal describing the classification and retrieval tasks, which are based on functional similarities according to structural and semantic closeness. To this effect, we define four partial ordering relations among reusable components and several measures to quantify functional differences among them. By using these measures, we are able to offer an approximate and efficient retrieval, without formal proofs, and to predict adaptation efforts to satisfy the required functionality.
Molecular Mechanisms of Germline Stem Cell Regulation
Authors: Wong Marco D. , Jin Zhigang , Xie Ting
Published: August 2005

Germline stem cells (GSCs), which can self-renew and generate differentiated progeny, are unique stem cells in that they are solely dedicated to reproduction and transmit genetic information from generation to generation. Through the use of genetic techniques in Drosophila, Caenorhabditis elegans, and mouse, exciting progress has been made in understanding molecular mechanisms underlying interactions between stem cells and niches. The knowledge gained from studying GSCs has provided an intellectual framework for defining niches and molecular regulatory mechanisms for other adult stem cells. In this review, we summarize recent progress and discuss conserved mechanisms underlying GSC self-renewal and differentiation by comparing three GSC systems. Because GSCs and other adult stem cells share “stemness,” we hope this review will help define fundamental principles of stem cell regulation and provide further guidance for future studies of other adult stem cells.
Orthologs, Paralogs, and Evolutionary Genomics
Authors: Koonin Eugene V.
Published: August 2005

Orthologs and paralogs are two fundamentally different types of homologous genes that evolved, respectively, by vertical descent from a single ancestral gene and by duplication. Orthology and paralogy are key concepts of evolutionary genomics. A clear distinction between orthologs and paralogs is critical for the construction of a robust evolutionary classification of genes and reliable functional annotation of newly sequenced genomes. Genome comparisons show that orthologous relationships with genes from taxonomically distant species can be established for the majority of the genes from each sequenced genome. This review examines in depth the definitions and subtypes of orthologs and paralogs, outlines the principal methodological approaches employed for identification of orthology and paralogy, and considers evolutionary and functional implications of these concepts.
On generalized ω‐closed sets
Authors: Al-Zoubi Khalid Y.
Published: August 2005

The class of ω‐closed subsets of a space
(X, τ) was defined to introduce ω‐closed functions. The aim of this paper is to introduce and study the class of
gω‐closed sets. This class of sets is finer than g‐closed
sets and ω‐closed sets. We study the fundamental properties
of this class of sets. In the space (X, τω), the concepts closed set, g‐closed set, and gω‐closed set
coincide. Further, we introduce and study gω‐continuous and
gω‐irresolute functions.
Symmetry breaking via internal geometry
Authors: Talmadge Andrew
Published: August 2005

Gauge theories commonly employ complex vector‐valued fields to
reduce symmetry groups through the Higgs mechanism of
spontaneous symmetry breaking. The geometry of the internal space
V is tacitly assumed to be the metric geometry of some static,
nondynamical hermitian metric k. In this paper, we consider
G‐principal bundle gauge theories, where G is a subgroup of
U(V, k) (the unitary transformations on the internal vector space
V with hermitian metric k) and we consider allowing the
hermitian metric on the internal space V to become an additional
dynamical element of the theory. We find a mechanism for
interpreting the Higgs scalar field as a feature of the geometry
of the internal space while retaining the successful aspects of
the Higgs mechanism and spontaneous symmetry breaking
Additive functionals and excursions of Kuznetsov processes
Authors: Boutabia Hacène
Published: August 2005

Let B be a continuous additive functional for a standard process and let be a stationary Kuznetsov process with the same
semigroup of transition. In this paper, we give the excursion laws of conditioned on the strict past and future without duality hypothesis. We study excursions of a general regenerative system and of a regenerative system consisting of the closure of the set of times the regular points of B are visited. In both cases, those conditioned excursion laws depend only on two points and Xd, where ]g, d[ is an excursion interval of the regenerative set M. We use the ‐predictable exit system to bring together the isolated points of M and its perfect part and replace the classical optional exit system. This has been a subject in literature before (e.g., Kaspi (1988)) under the classical duality hypothesis. We define an “additive functional” for with B, we generalize the laws cited before to , and we express laws of pairs of excursions.
Noetherian and Artinian ordered groupoids—semigroups
Authors: Kehayopulu Niovi , Tsingelis Michael
Published: August 2005

Chain conditions, finiteness conditions, growth conditions, and
other forms of finiteness, Noetherian rings and Artinian rings
have been systematically studied for commutative rings
and algebras since 1959. In pursuit of the deeper results of ideal
theory in ordered groupoids (semigroups), it is necessary to study
special classes of ordered groupoids (semigroups). Noetherian
ordered groupoids (semigroups) which are about to be
introduced are particularly versatile. These satisfy a
certain finiteness condition, namely, that every ideal of the
ordered groupoid (semigroup) is finitely generated. Our purpose
is to introduce the concepts of Noetherian and Artinian ordered
groupoids. An ordered groupoid is said to be Noetherian if every
ideal of it is finitely generated. In this paper, we prove that an
equivalent formulation of the Noetherian requirement is that the
ideals of the ordered groupoid satisfy the so‐called ascending
chain condition. From this idea, we are led in a natural way to
consider a number of results relevant to ordered groupoids with
descending chain condition for ideals. We moreover prove that an
ordered groupoid is Noetherian if and only if it satisfies the
maximum condition for ideals and it is Artinian if and only if it
satisfies the minimum condition for ideals. In addition, we prove
that there is a homomorphism π of an ordered groupoid
(semigroup) S having an ideal I onto the Rees
quotient ordered groupoid (semigroup) S/I. As a
consequence, if S is an ordered groupoid and I an ideal of
S such that both I and the quotient groupoid S/I are Noetherian (Artinian), then so is S. Finally, we give
conditions under which the proper prime ideals of commutative
Artinian ordered semigroups are maximal ideals.
A characterization of the four Chebyshev orthogonal families
Authors: Berriochoa E. , Cachafeiro A. , Garcia-Amor J. M.
Published: August 2005

We obtain a property which characterizes the Chebyshev
orthogonal polynomials of first, second, third, and fourth kind.
Indeed, we prove that the four Chebyshev sequences are the unique
classical orthogonal polynomial families such that their
linear combinations, with fixed length and constant coefficients, can be orthogonal polynomial
sequences.
Switchings, realizations, and interpolation theorems for graph parameters
Authors: Punnim Narong
Published: August 2005

Interpolation theorems on several graph parameters obtained in the
past few years will be reviewed in this paper. Some simplified
proofs are provided. Open problems in this direction are reviewed.
On a problem on explicit embeddings of the group ℚ
Authors: Mikaelian Vahagn H.
Published: August 2005

Answering a question of de la Harpe and Bridson in the
Kourovka Notebook, we build the explicit embeddings of the additive group of rational numbers ℚ in a finitely generated group G. The group G in
fact is two‐generator, and the constructed embedding can be
subnormal and preserve a few properties such as solubility or
torsion freeness.
Derived categories and the analytic approach to generalreciprocity laws. Part I
Authors: Berg Michael
Published: August 2005

We reformulate Hecke′s open problem of 1923, regarding the
Fourier‐analytic proof of higher reciprocity laws, as a theorem
about morphisms involving stratified topological spaces. We
achieve this by placing Kubota′s formulations of n‐Hilbert
reciprocity in a new topological context, suited to the
introduction of derived categories of sheaf complexes.
Subsequently, we begin to investigate conditions on associated
sheaves and a derived category of sheaf complexes specifically
designed for an attack on Hecke′s eighty‐year‐old challenge.
Symmetry properties of a generalized Korteweg‐de Vries equation and some explicit solutions
Authors: Bracken Paul
Published: August 2005

The symmetry group method is applied to a generalized Korteweg‐de
Vries equation and several classes of group invariant solutions
for it are obtained by means of this technique. Polynomial,
trigonometric, and elliptic function solutions can be calculated.
It is shown that this generalized equation can be reduced to a
first‐order equation under a particular second‐order differential
constraint which resembles a Schrödinger equation. For a
particular instance in which the constraint is satisfied, the
generalized equation is reduced to a quadrature. A condition which
ensures that the reciprocal of a solution is also a solution is
given, and a first integral to this constraint is found.
Glutathione and Ascorbic Acid Enhance Recovery of Guinea Pig Spinal Cord White Matter Following Ischemia and Acrolein Exposure
Authors: Logan Melissa Peasley , Parker Steven , Shi Riyi
Published: August 2005

Objective: We have shown that acrolein, a lipid peroxidation byproduct, can inflict significant damage in isolated spinal cord white matter following oxygen glucose deprivation (OGD). The mechanism of such acrolein-induced damage is unclear. The aim of this study was to examine whether glutathione (GSH) and ascorbic acid, two reactive oxygen species (ROS) scavengers, can alleviate functional and anatomical damage due to acrolein. Methods: We used an OGD injury model with isolated guinea pig spinal cord white matter. Sucrose gap recording was used to monitor axonal impulse conduction, and a horseradish peroxidase exclusion test was employed to determine membrane integrity. The functional and anatomical parameters were compared in three groups: acrolein, acrolein/GSH and acrolein/ascorbic acid. Results: We found that while GSH resulted in an 87% recovery of compound action potential conductance, ascorbic acid produced a 97% recovery, compared with a 69% recovery in an injured group without treatment. It is noted that GSH, and to a lesser extent ascorbic acid, preferentially enhanced functional recovery in smaller axons. Conclusion: Acrolein-induced neuronal damage is likely mediated by ROS. Furthermore, GSH and ascorbic acid are effective in suppressing acrolein and free radical-induced injury in spinal cord white matter.
Expression of p53 Protein in Esophageal Squamous Cell Carcinoma: Relation to Hypoxia-Inducible Factor-1α, Angiogenesis and Apoptosis
Authors: Kimura Shigeru , Kitadai Yasuhiko , Kuwai Toshio , Tanaka Shinji , Hihara Jun , Yoshida Kazuhiro , Toge Tetsuya , Chayama Kazuaki
Published: August 2005

Objectives: Hypoxia-inducible factor (HIF)-1 is important in the control of transcription of several genes related to angiogenesis. We have previously reported that expression of HIF-1α correlates with venous invasion and clinical outcome in esophageal squamous cell carcinoma. p53 has been reported to interact with HIF-1α and induce ubiquitin-mediated proteosomal degradation of HIF-1α. The purpose of this study was to clarify whether the expression of p53 is associated with that of HIF-1α. Methods: Expression of p53, HIF-1α and vascular endothelial growth factor (VEGF) was examined in 81 archival surgical specimens of human esophageal squamous cell carcinoma tissue. CD34 and single-stranded DNA were used to evaluate angiogenesis and apoptosis. Results: Forty-seven of the 81 (58.0%) tumor specimens showed high levels of nuclear p53 immunoreactivity. Overexpression of p53 was observed in the early clinical stage of tumor development. Expression of p53 was not correlated with HIF-1α or VEGF expression, angiogenesis or apoptosis in esophageal carcinoma. Conclusions: These results suggest that mutations in p53 play a role in carcinogenesis but not in the progression of esophageal squamous cell carcinoma. HIF-1α may not only be regulated by p53 but also by other factors.