bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Regulation of Ceramide Synthase Components
LAC1
and
LAG1
in
Saccharomyces cerevisiae
Authors: Kolaczkowski Marcin , Kolaczkowska Anna , Gaigg Barbara , Schneiter Roger , Moye-Rowley W. Scott
Published: August 2004

In
Saccharomyces cerevisiae
, the essential ceramide synthase reaction requires the presence of one of a homologous pair of genes,
LAG1
and
LAC1
. Mutants that lack both of these genes cannot produce ceramide and exhibit a striking synthetic growth defect. While the regulation of ceramide production is critical for the control of proliferation and for stress tolerance, little is known of the mechanisms that ensure proper control of this process. The data presented here demonstrate that the pleiotropic drug resistance (Pdr) regulatory pathway regulates the transcription of multiple genes encoding steps in sphingolipid biosynthesis, including
LAC1
. The zinc cluster transcriptional activators Pdr1p and Pdr3p bind to Pdr1p/Pdr3p-responsive elements (PDREs) in the promoters of Pdr pathway target genes.
LAC1
contains a single PDRE in its promoter, but notably,
LAG1
does not. Reporter gene, Northern blot, and Western blot assays indicated that the expression level of Lac1p is approximately three times that of Lag1p. Detailed analyses of the
LAC1
promoter demonstrated that transcription of this gene is inhibited by the presence of the transcription factor Cbf1p and the anaerobic repressor Rox1p.
LAG1
transcription was also elevated in
cbf1
Δ cells, indicating at least one common regulatory input. Although a hyperactive Pdr pathway altered the profile of sphingolipids produced, the loss of either
LAC1
or
LAG1
alone failed to produce further changes. Two other genes involved in sphingolipid biosynthesis (
LCB2
and
SUR2
) were found to contain PDREs in their promoters and to be induced by the Pdr pathway. These data demonstrate extensive coordinate control of sphingolipid biosynthesis and multidrug resistance in yeast.
Role of a 300-Kilodalton Nuclear Complex in the Maturation of
Trypanosoma brucei
Initiator Methionyl-tRNA
Authors: Arhin George K. , Shen Shuiyuan , Irmer Henriette , Ullu Elisabetta , Tschudi Christian
Published: August 2004

tRNAs are transcribed as precursors containing 5′ leader and 3′ extensions that are removed by a series of posttranscriptional processing reactions to yield functional mature tRNAs. Here, we examined the maturation pathway of tRNA
Met
in
Trypanosoma brucei
, an early divergent unicellular eukaryote. We identified an approximately 300-kDa complex located in the nucleus of
T. brucei
that is required for trimming the 5′ leader of initiator tRNA
Met
precursors. One of the subunits of the complex (
T. brucei
MT40 [TbMT40]) is a putative methyltransferase and a homolog of
Saccharomyces cerevisiae
Gcd14, which is essential for 1-methyladenosine modification in tRNAs. Down-regulation of TbMT40 by RNA interference resulted in the accumulation of precursor initiator tRNA
Met
containing 5′ extensions but processed 3′ ends. In addition, immunoprecipitations with anti-La antibodies revealed initiator tRNA
Met
molecules with 5′ and 3′ extensions in TbMT40-silenced cells, albeit at a much lower level. Interestingly, silencing of TbMT40, as well as of TbMT53, a second subunit of the complex, led to an increase in the levels of mature elongator tRNA
Met
. Taken together, our data provide a glance at the maturation of tRNAs in parasitic protozoa and suggest that at least for initiator tRNA
Met
, 3′ trimming precedes 5′ processing.
Ectopic Expression of
URA3
Can Influence the Virulence Phenotypes and Proteome of
Candida albicans
but Can Be Overcome by Targeted Reintegration of
URA3
at the
RPS10
Locus
Authors: Brand Alexandra , MacCallum Donna M. , Brown Alistair J. P. , Gow Neil A. R. , Odds Frank C.
Published: August 2004

Uridine auxotrophy, based on disruption of both
URA3
alleles in diploid
Candida albicans
strain SC5314, has been widely used to select gene deletion mutants created in this fungus by “Ura-blasting” and PCR-mediated disruption. We compared wild-type
URA3
expression with levels in mutant strains where
URA3
was positioned either within deleted genes or at the highly expressed
RPS10
locus.
URA3
expression levels differed significantly and correlated with the specific activity of Ura3p, orotidine 5′-monophosphate decarboxylase. Reduced
URA3
expression following integration at the
GCN4
locus was associated with an attenuation of virulence. Furthermore, a comparison of the SC5314 (
URA3
) and CAI-4 (
ura3
) proteomes revealed that inactivation of
URA3
caused significant changes in the levels of 14 other proteins. The protein levels of all except one were partially or fully restored by the reintegration of a single copy of
URA3
at the
RPS10
locus. Transcript levels of genes expressed ectopically at this locus in reconstituted heterozygous mutants also matched the levels found when the genes were expressed at their native loci. Therefore, phenotypic changes in
C. albicans
can be associated with the selectable marker rather than the target gene. Reintegration of
URA3
at an appropriate expression locus such as
RPS10
can offset most problems related to the phenotypic changes associated with gene knockout methodologies.
RSC1
and
RSC2
Are Required for Expression of Mid-Late Sporulation-Specific Genes in
Saccharomyces cerevisiae
Authors: Bungard David , Reed Michelle , Winter Edward
Published: August 2004

Rsc1 and Rsc2 are alternative bromodomain-containing subunits of the ATP-dependent RSC chromatin remodeling complex in
Saccharomyces cerevisiae
. Smk1 is a sporulation-specific mitogen-activated protein kinase homolog that is required for the postmeiotic events of spore formation. In this study we show that
RSC1
and
RSC2
are haploinsufficient for spore formation in a
smk1
hypomorph. Moreover, diploids lacking Rsc1 or Rsc2 show a subset of
smk1
-like phenotypes. High-copy-number
RSC1
plasmids do not suppress
rsc2-
Δ/
rsc2-
Δ sporulation defects, and high-copy-number
RSC2
plasmids do not suppress
rsc1-
Δ/
rsc1-
Δ sporulation defects. Mid-late sporulation-specific genes, which are normally expressed while key steps in spore assembly occur and which include genes that are required for spore wall formation, are not expressed in cells lacking Rsc1 or Rsc2. We speculate that the combined action of Rsc1 and Rsc2 at mid-late promoters is specifically required for the proper expression of this uniquely timed set of genes. Our data suggest that Smk1 and Rsc1/2 define parallel pathways that converge to provide signaling information and the expression of gene products, respectively, that are required for spore morphogenesis.
Gpr1, a Putative G-Protein-Coupled Receptor, Regulates Morphogenesis and Hypha Formation in the Pathogenic Fungus
Candida albicans
Authors: Miwa Takuya , Takagi Yukinobu , Shinozaki Makiko , Yun Cheol-Won , Schell Wiley A. , Perfect John R. , Kumagai Hidehiko , Tamaki Hisanori
Published: August 2004

In response to various extracellular signals, the morphology of the human fungal pathogen
Candida albicans
switches from yeast to hypha form. Here, we report that
GPR1
encoding a putative G-protein-coupled receptor and
GPA2
encoding a Gα subunit are required for hypha formation and morphogenesis in
C. albicans
. Mutants lacking Gpr1 (
gpr1/gpr1
) or Gpa2 (
gpa2/gpa2
) are defective in hypha formation and morphogenesis on solid hypha-inducing media. These phenotypic defects in solid cultures are suppressed by exogenously added dibutyryl-cyclic AMP (dibutyryl-cAMP). Biochemical studies also reveal that
GPR1
and
GPA2
are required for a glucose-dependent increase in cellular cAMP. An epistasis analysis indicates that Gpr1 functions upstream of Gpa2 in the same signaling pathway, and a two-hybrid assay reveals that the carboxyl-terminal tail of Gpr1 interacts with Gpa2. Moreover, expression levels of
HWP1
and
ECE1
, which are cAMP-dependent hypha-specific genes, are reduced in both mutant strains. These findings support a model that Gpr1, as well as Gpa2, regulates hypha formation and morphogenesis in a cAMP-dependent manner. In contrast,
GPR1
and
GPA2
are not required for hypha formation in liquid fetal bovine serum (FBS) medium. Furthermore, the
gpr1
and the
gpa2
mutant strains are fully virulent in a mouse infection. These findings suggest that Gpr1 and Gpa2 are involved in the glucose-sensing machinery that regulates morphogenesis and hypha formation in solid media via a cAMP-dependent mechanism, but they are not required for hypha formation in liquid medium or during invasive candidiasis.
Discovery of Cercosporamide, a Known Antifungal Natural Product, as a Selective Pkc1 Kinase Inhibitor through High-Throughput Screening
Authors: Sussman Andrea , Huss Karen , Chio Li-Chun , Heidler Steve , Shaw Margaret , Ma Doreen , Zhu Guoxin , Campbell Robert M. , Park Tae-Sik , Kulanthaivel Palaniappan , Scott John E. , Carpenter John W. , Strege Mark A. , Belvo Matthew D. , Swartling James R. , Fischl Anthony , Yeh Wu-Kuang , Shih Chuan , Ye Xiang S.
Published: August 2004

The Pkc1-mediated cell wall integrity-signaling pathway is highly conserved in fungi and is essential for fungal growth. We thus explored the potential of targeting the Pkc1 protein kinase for developing broad-spectrum fungicidal antifungal drugs through a
Candida albicans
Pkc1-based high-throughput screening. We discovered that cercosporamide, a broad-spectrum natural antifungal compound, but previously with an unknown mode of action, is actually a selective and highly potent fungal Pkc1 kinase inhibitor. This finding provides a molecular explanation for previous observations in which
Saccharomyces cerevisiae
cell wall mutants were found to be highly sensitive to cercosporamide. Indeed,
S. cerevisiae
mutant cells with reduced Pkc1 kinase activity become hypersensitive to cercosporamide, and this sensitivity can be suppressed under high-osmotic growth conditions. Together, the results demonstrate that cercosporamide acts selectively on Pkc1 kinase and, thus, they provide a molecular mechanism for its antifungal activity. Furthermore, cercosporamide and a β-1,3-glucan synthase inhibitor echinocandin analog, by targeting two different key components of the cell wall biosynthesis pathway, are highly synergistic in their antifungal activities. The synergistic antifungal activity between Pkc1 kinase and β-1,3-glucan synthase inhibitors points to a potential highly effective combination therapy to treat fungal infections.
Proteomic Analysis of
Candida albicans
Cell Walls Reveals Covalently Bound Carbohydrate-Active Enzymes and Adhesins
Authors: de Groot Piet W. J. , de Boer Albert D. , Cunningham Jeff , Dekker Henk L. , de Jong Luitzen , Hellingwerf Klaas J. , de Koster Chris , Klis Frans M.
Published: August 2004

Covalently linked cell wall proteins (CWPs) of the dimorphic fungus
Candida albicans
are implicated in virulence. We have carried out a comprehensive proteomic analysis of the covalently linked CWPs in exponential-phase yeast cells. Proteins were liberated from sodium dodecyl sulfate (SDS)-extracted cell walls and analyzed using immunological and advanced protein sequencing (liquid chromatography-tandem mass spectrometry [LC/MS/MS]) methods. HF-pyridine and NaOH were used to chemically release glycosylphosphatidylinositol-dependent proteins (GPI proteins) and mild alkali-sensitive proteins, respectively. In addition, to release both classes of CWPs simultaneously, cell walls were digested enzymatically with a recombinant β-1,3-glucanase. Using LC/MS/MS, we identified 14 proteins, of which only 1 protein, Cht2p, has been previously identified in cell wall extracts by using protein sequencing methods. The 14 identified CWPs include 12 GPI proteins and 2 mild alkali-sensitive proteins. Nonsecretory proteins were absent in our cell wall preparations. The proteins identified included several functional categories: (i) five CWPs are predicted carbohydrate-active enzymes (Cht2p, Crh11p, Pga4p, Phr1p, and Scw1p); (ii) Als1p and Als4p are believed to be adhesion proteins. In addition, Pga24p shows similarity to the flocculins of baker's yeast. (iii) Sod4p/Pga2p is a putative superoxide dismutase and is possibly involved in counteracting host defense reactions. The precise roles of the other CWPs (Ecm33.3p, Pir1p, Pga29p, Rbt5p, and Ssr1p) are unknown. These results indicate that a substantial number of the covalently linked CWPs of
C. albicans
are actively involved in cell wall remodeling and expansion and in host-pathogen interactions.
Dehydration-Specific Induction of Hydrophilic Protein Genes in the Anhydrobiotic Nematode
Aphelenchus avenae
Authors: Browne John A. , Dolan Katharine M. , Tyson Trevor , Goyal Kshamata , Tunnacliffe Alan , Burnell Ann M.
Published: August 2004

Some organisms can survive exposure to extreme desiccation by entering a state of suspended animation known as anhydrobiosis. The free-living nematode
Aphelenchus avenae
can be induced to enter the anhydrobiotic state by exposure to a moderate reduction in relative humidity. During this preconditioning period, the nematode accumulates large amounts of the disaccharide trehalose, which is thought to be necessary, but not sufficient, for successful anhydrobiosis. To identify other adaptations that are required for anhydrobiosis, we developed a novel SL1-based mRNA differential display technique to clone genes that are upregulated by dehydration in
A. avenae
. Three such genes,
Aav-lea-1
,
Aav-ahn-1
, and
Aav-glx-1
, encode, respectively, a late embryogenesis abundant (LEA) group 3 protein, a novel protein that we named anhydrin, and the antioxidant enzyme glutaredoxin. Strikingly, the predicted LEA and anhydrin proteins are highly hydrophilic and lack significant secondary structure in the hydrated state. The dehydration-induced upregulation of
Aav-lea-1
and
Aav-ahn-1
was confirmed by Northern hybridization and quantitative PCR experiments. Both genes were also upregulated by an osmotic upshift, but not by cold, heat, or oxidative stress. Experiments to investigate the relationship between mRNA levels and protein expression for these genes are in progress. LEA proteins occur commonly in plants, accumulating during seed maturation and desiccation stress; the presence of a gene encoding an LEA protein in an anhydrobiotic nematode suggests that some mechanisms of coping with water loss are conserved between plants and animals.
Direct Physical and Functional Interaction of the NuA4 Complex Components Yaf9p and Swc4p
Authors: Bittner Claudia B. , Zeisig Deniz T. , Zeisig Bernd B. , Slany Robert K.
Published: August 2004

Saccharomyces cerevisiae
Yaf9p and the mammalian leukemia-associated protein ENL share a high degree of similarity. To investigate the biological function of Yaf9p, this protein was used to search for interacting proteins in a two-hybrid system. Here, we demonstrate that Yaf9p binds directly to Swc4p, the yeast homolog of the mammalian DNA-methyltransferase-associated protein 1. Yaf9p and Swc4p associate through C-terminal domains, and both proteins coprecipitate in vitro in pull-down experiments and in vivo by immunoprecipitation. In living cells, Swc4p is present in a megadalton protein complex that shows a fractionation behavior in gel filtration similar to that of Esa1p, the histone acetyltransferase of the NuA4 complex. Recruitment of Yaf9p to DNA leads to promoter-specific transcriptional activation that can be inhibited by dominant negative Swc4p lacking the Yaf9p binding domain. Interference with Swc4p function also increases sensitivity to the microtubule toxin benomyl, a trait that corresponds to the known phenotype of a
yaf9
−
knockout strain. In summary, the results suggest that Yaf9p and Swc4p form a protein pair that has a role in chromatin modification with possible implications also for the function of their mammalian counterparts.
CHPA, a Cysteine- and Histidine-Rich-Domain-Containing Protein, Contributes to Maintenance of the Diploid State in
Aspergillus nidulans
Authors: Sadanandom Ari , Findlay Kim , Doonan John H. , Schulze-Lefert Paul , Shirasu Ken
Published: August 2004

The alternation of eukaryotic life cycles between haploid and diploid phases is crucial for maintaining genetic diversity. In some organisms, the growth and development of haploid and diploid phases are nearly identical, and one might suppose that all genes required for one phase are likely to be critical for the other phase. Here, we show that targeted disruption of the
chpA
(cysteine- and histidine-rich-domain- [CHORD]-containing protein A) gene in haploid
Aspergillus nidulans
strains gives rise to
chpA
knockout haploids and heterozygous diploids but no
chpA
knockout diploids.
A. nidulans chpA
heterozygous diploids showed impaired conidiophore development and reduced conidiation. Deletion of
chpA
from diploid
A. nidulans
resulted in genome instability and reversion to a haploid state. Thus, our data suggest a vital role for
chpA
in maintenance of the diploid phase in
A. nidulans
. Furthermore, the human
chpA
homolog,
Chp-1
, was able to complement haploinsufficiency in
A. nidulans chpA
heterozygotes, suggesting that the function of CHORD-containing proteins is highly conserved in eukaryotes.
Dynamics of
Toxoplasma gondii
Differentiation
Authors: Dzierszinski Florence , Nishi Manami , Ouko Lillian , Roos David S.
Published: August 2004

Parasite differentiation is commonly associated with transitions between complex life cycle stages and with long-term persistence in the host, and it is therefore critical for pathogenesis. In the protozoan parasite
Toxoplasma gondii
, interconversion between rapidly growing tachyzoites and latent encysted bradyzoites is accompanied by numerous morphological and metabolic adaptations. In order to explore early cell biological events associated with this differentiation process, we have exploited fluorescent reporter proteins targeted to various subcellular locations. Combining these markers with efficient in vitro differentiation and time-lapse video microscopy provides a dynamic view of bradyzoite development in living cultures, demonstrating subcellular reorganization, maintenance of the mitochondrion, and missegregation of the apicoplast. Bradyzoites divide asynchronously, using both endodyogeny and endopolygeny, and are highly motile both within and between host cells. Cysts are able to proliferate without passing through an intermediate tachyzoite stage, via both the migration of free bradyzoites and the fission of bradyzoite cysts, suggesting a mechanism for dissemination during chronic infection.
Repetitive strain injury
Authors: Helliwell P S , Taylor W J
Published: August 2004

Pain in the forearm is relatively common in the community. In the workplace forearm pain is associated with work involving frequent repetition, high forces, and prolonged abnormal postures. Nevertheless, other factors are involved in the presentation and the continuation of the pain. Notable among these factors are psychosocial issues and the workplace environment—the attitude to workers and their welfare, the physical conditions, and design of the job. Primary prevention may be effective but active surveillance is important with early intervention and an active management approach. Physical treatments have not been extensively evaluated. In the established case, management should be multidisciplinary, addressing physical aspects of the job but also addressing the “yellow, blue, and black flags” which should be viewed as obstacles to recovery. For the worker “on sick” a dialogue should be established between the worker, the primary care physician, and the workplace. Return to work should be encouraged and facilitated by medical interventions and light duty options. Rehabilitation programmes may be of use in chronic cases.
Long term motor complications of levodopa: clinical features, mechanisms, and management strategies
Authors: Thanvi B R , Lo T C N
Published: August 2004

Levodopa is the most effective symptomatic treatment of Parkinson’s disease. However, after an initial period of dramatic benefit, several limitations become apparent including, “dopa resistant” motor symptoms (postural abnormalities, freezing episodes, speech impairment), “dopa resistant” non-motor signs (autonomic dysfunction, mood and cognitive impairment, etc), and/or drug related side effects (especially psychosis, motor fluctuations, and dyskinesias). Motor complications include fluctuations, dyskinesias, and dystonias. They can be very disabling and difficult to treat. Therefore, strategies should ideally be developed to prevent them. Though mechanisms underlying motor complications are only partially understood, recent work has revealed the importance of pulsatile stimulation of postsynaptic dopamine receptors and the disease severity. As a result of intermittent stimulation there occurs a cascade of changes in cell signalling leading to upregulation of the N-methyl-D-aspartate subtype of gamma-aminobutryric acid-ergic neurones. Modified preparations of levodopa (controlled release preparations, liquid levodopa), catecholamine-o-methyltransferase inhibitors, dopamine agonists, amantidine, and various neurosurgical approaches have been used in the prevention and/or treatment of motor complications. Current management of motor complications is less than satisfactory. With better understanding of the pathogenetic mechanisms, it is hoped that future therapeutic strategies will provide a safer and targeted treatment.
Probiotics and prebiotics in the elderly
Authors: Hamilton-Miller J M T
Published: August 2004

Probiotics (usually lactobacilli and bifidobacteria) and prebiotics (non-digestible oligosaccharides) have been shown to be useful in preventing certain disease conditions as well as possibly promoting specific aspects of health. In the present review, the evidence from clinical trials for benefits from probiotics and prebiotics to elderly populations is presented and discussed, specifically in respect of three common conditions found in the elderly. Both probiotics and prebiotics may be helpful in malnutrition, particularly in lactose intolerance and calcium absorption, and in constipation. Probiotics have been shown clearly to boost immunity in the elderly, but the clinical significance of this remains to be clarified. These results are encouraging, and further large scale studies seem justified to establish the place of probiotic and prebiotic supplements in elderly subjects.
Observation and identification of lactate dehydrogenase anomaly in a postburn patient
Authors: Liu Z-J , Zhang Y , Zhang X-B , Yang X
Published: August 2004

Objective: Lactate dehydrogenase (LDH) anomaly is one of the macroenzymes. Macroenzymes are enzymes in serum that have formed high molecular mass complexes, either by self polymerisation or by association with other serum components. The aim of this study was to identify the properties of LDH anomaly and observe the changes from admission to discharge in a postburn patient with LDH anomaly in his serum.

Methods: LDH isoenzymes of the serum were electrophoretically fractionated with terylene cellulose acetate supporting media; LDH anomaly was identified by counter immunoelectrophoresis.

Results: An abnormal LDH-4 band and an extra band on the cathode of LDH-5 were observed in the serum of this patient and were found to be part of an LDH-IgG complex. As his symptoms improved, the patient’s LDH anomaly gradually disappeared. The appearance and disappearance of the anomaly seemed to be related to the progression of the patient’s burns.

Conclusion: In clinical practice, it is important to keep in mind the possibility of an LDH anomaly in patients when the LDH level is abnormally high or does not seem to be related to the clinical state. Early discovery of an LDH anomaly in a patient’s serum may be useful for diagnosis and treatment.
Evaluation of the role of a specialist tracheostomy service. From critical care to outreach and beyond
Authors: Norwood M G A , Spiers P , Bailiss J , Sayers R D
Published: August 2004

The impact that a new specialist tracheostomy service, designed specifically for the care of patients with tracheostomies, was assessed in terms of type of tracheostomy tube used, time to first tube change, time to decannulation, and incidence of tracheostomy related complications in a teaching hospital with no on-site ear, nose, and throat facility. A total of 170 patients were studied. After service implementation, fewer patients (17.6%, n = 21) were discharged from the intensive treatment unit to the wards with tracheostomy tubes compared with the first group (39%, n = 20) (p = 0.006), and the number of tracheostomy related complications on the wards were significantly reduced (p = 0.031).
A case of two adverse reactions
Authors: Smith L-A , Harkness M
Published: August 2004

Low molecular weight heparins are now widely prescribed in the treatment of thromboembolic disease and acute coronary syndromes. Anaphylaxis is a recognised but rare potentially life threatening side effect of heparin.

Common clinical features of anaphylaxis are cardiovascular collapse, bronchospasm, cutaneous symptoms, angioedema, generalised oedema, or gastrointestinal symptoms. It is extremely rare, however, for patients to experience such dramatic and potentially life threatening consequences as seen in the case reported here. It has been shown that patients may be tolerant of certain low molecular weight heparins but sensitive to others.

Adrenaline is regarded as the most important drug for any severe anaphylactic reaction. Administration by the intramuscular route produces significantly higher peak plasma concentrations compared with subcutaneous injection, which is clearly beneficial in the critically compromised patient. Current UK Resuscitation Council guidelines support the use of 0.5 ml of 1:1000 adrenaline to be administered intramuscularly.
Life threatening hyperphosphataemia after administration of sodium phosphate in preparation for colonoscopy
Authors: Azzam I , Kovalev Y , Storch S , Elias N
Published: August 2004

An elderly woman developed severe hyperphosphataemia, hypocalcaemia, and cardiac arrest after oral administration of sodium phosphate in preparation for colonoscopy. This is an unusual complication and is attributed to decreased phosphate excretion by the kidneys. At increased risk are patients with impaired renal function, age more than 65 years, and presenting with intestinal obstruction or decreased intestinal motility, increased intestinal permeability, liver cirrhosis, or congestive heart failure. Though there are no accepted guidelines for anticipation and prevention of this adverse effect, it may be desirable to check serum phosphate concentrations before choosing the method for colonic preparation and before giving the second oral dose of sodium phosphate in patients at risk. Hyperphosphataemia should be suspected if a patient develops hypotension or neuromuscular irritability after administration of sodium phosphate. Haemodialysis for direct removal of phosphate and intravenous calcium for treatment of symptomatic hypocalcaemia may be life saving.
Patient and disease profile of emergency medical readmissions to an Irish teaching hospital
Authors: Moloney E D , Bennett K , Silke B
Published: August 2004

Objective: To determine whether there was a relationship between coded diseases at the time of hospital discharge, a pattern of ordering investigations, and hospital readmission in a major teaching hospital.

Design: Systematic review of data relating to emergency medical patients admitted to St James’ Hospital Dublin between 1 January and 31 December 2002.

Data sources and methods: Data on discharges from hospital recorded in the Hospital In-Patient Enquiry (HIPE) system. The value of HIPE data in describing the relationship between the pattern of resource utilisation, diagnostic related groups, and hospital readmission has not previously been examined.

Results: Of 5038 episodes recorded among 4050 patients admitted, the number of readmissions was up to 15. Age and male gender were factors associated with readmission, and readmitted patients remained in hospital for longer. No particular test request predicted readmission, but computed tomography of the brain was associated with a reduced readmission rate. Discharge diagnostic related group coding at first discharge predicted readmission—codes related to heart failure, respiratory system, alcohol, malignancy, and anaemia.

Conclusions: It was found that clinical coding using the HIPE database strongly predicted hospital readmission. It may be argued that early hospital readmission reflects unsatisfactory patient care, alternatively that many readmissions are not preventable, representing either new events in elderly patients with chronic illnesses and frequent co-morbidity or related to social factors. The utility of specific interventions, in patients at high risk for hospital readmission, could be explored.
History of medical screening: from concepts to action
Authors: Morabia A , Zhang F F
Published: August 2004

The objective of medical screening is to identify disease in its preclinical, and therefore hopefully still curable, phase. This may have been an old quest in medicine but it became historically possible when at least four conditions were met: the availability of simple, valid and acceptable forms of tests, the discovery of effective treatments, the establishment of a theory of screening, and the wide access to health care. Five selected examples that illustrate the history of medical screening are reviewed: screening for psychiatric disorders in the United States army as it is one of the oldest screening programmes; screening for syphilis as it used one of the earliest screening tests; screening for diabetes as one of the first modern forms of mass screening; screening for cervical cancer using the Pap test as one of the greatest successes of screening; and screening for breast cancer by mammography as this offers a good opportunity to discuss the development of modern evaluation of screening programmes. The evaluation of the impact of screening on human health slowly progressed, from obvious changes in the vital statistics such as the decline in incidence of syphilis, to less obvious changes such as the decline in mortality of cancer of the uterus, to finally more subtle changes, such as the impact of mammographic screening on breast cancer mortality. Methods of evaluation had therefore to adapt, evolving from simple surveys to case-control studies and randomised trials. The history of screening is short, but very rich and mostly still to be written.
ENTROPY CALCULATION OF A KERR–NEWMAN BLACK HOLE VIA THE THIN FILM BRICK-WALL MODEL
Authors: ZHOU ZHOU'AN , LIU WENBIAO
Published: August 2004

Applying the powerful thin film brick-wall model to the general Kerr–Newman black hole, we find out that the entropy calculation result can also satisfy the area theorem. Moreover, the area theorem is not only satisfied for the global black hole, but also for every area cell on its horizon, that means, every cell on the horizon contributes its own part of entropy if we choose a same temperature-related radial cutoff ε'. This new thin film brick-wall model can be used to calculate dynamic black hole which has different temperatures on the horizon. It tells us that the horizon is exactly the statistical origin of a black hole entropy, the total entropy of a black hole is just the sum of all the contributions from every area cell. For a Kerr–Newman black hole, there is also an important difference between the thin film brick-wall model and the original one, that is, we do not need any angular cutoff in the thin film model, and this makes the physical meaning clearer.
FINITE-SIZE SCALING AND DECONFINEMENT TRANSITION: THE CASE OF 4D SU(2) PURE GAUGE THEORY
Authors: PAPA ALESSANDRO , VENA CARLO
Published: August 2004

A recently introduced method for determining the critical indices of the deconfinement transition in gauge theories, already tested for the case of 3D SU (3) pure gauge theory, is applied here to 4D SU (2) pure gauge theory. The method is inspired by universality and based on the finite size scaling behavior of the expectation value of simple lattice operators, such as the plaquette. We obtain an accurate determination of the critical index ν, in agreement with the prediction of the Svetitsky–Yaffe conjecture.
OBSERVABLES IN TOPOLOGICAL YANG–MILLS THEORIES
Authors: BOLDO JOSÉ LUÍS , CONSTANTINIDIS CLISTHENIS P. , PIGUET OLIVIER , GIERES FRANÇOIS , LEFRANÇOIS MATTHIEU
Published: August 2004

Using topological Yang–Mills theory as example, we discuss the definition and determination of observables in topological field theories (of Witten-type) within the superspace formulation proposed by Horne. This approach to the equivariant cohomology leads to a set of bi-descent equations involving the BRST and supersymmetry operators as well as the exterior derivative. This allows us to find the most general solution to the problem of equivariant cohomology, and to recover the Donaldson–Witten polynomials when choosing a Wess–Zumino-type gauge.
DARK MATTER DETECTION IN THE LIGHT OF RECENT EXPERIMENTAL RESULTS
Authors: MUÑOZ CARLOS
Published: August 2004

The existence of dark matter was suggested, using simple gravitational arguments, seventy years ago. Although we are now convinced that most of the mass in the Universe is indeed some nonluminous matter, we still do not know its composition. The problem of the dark matter in the Universe is reviewed here. Particle candidates for dark matter are discussed with particular emphasis on Weakly Interacting Massive Particles (WIMP's). Experiments searching for these relic particles, carried out by many groups around the world, are also reviewed, paying special attention to their direct detection by observing the elastic scattering on target nuclei through nuclear recoils. Finally, we concentrate on the theoretical models predicting WIMP's, and in particular on supersymmetric extensions of the standard model, where the leading candidate for WIMP, the neutralino, is present. There, we compute the cross-section for the direct detection of neutralinos, and compare it with the sensitivity of detectors. We mainly discuss supergravity, superstring and M theory scenarios.
FIVE-DIMENSIONAL QED, MUON PAIR PRODUCTION AND CORRECTION TO THE COULOMB POTENTIAL
Authors: NASCIMENTO J. R. S. , DE S. PIRES C. A. , RIBEIRO R. F.
Published: August 2004

We consider QED in five dimensions in a configuration where matter is localized on a 3-brane while foton propagates in the bulk. The idea is to investigate the effects of the Kaluza–Klein modes of the photon in the relativistic regime, but in low energy, and in the nonrelativistic regime. In the relativistic regime, we calculate the cross-section for the reaction e++e-→μ++μ-. We compare our theoretical result with a precise measurement of this cross-section at [Formula: see text]. As result, we extract a lower bound on the size of the extra dimension. In the nonrelativistic regime, we derive the contribution for the Coulomb potential due to the whole tower of the Kaluza–Klein excited modes of the photon. We use the modified potential to calculate the Rutherford scattering differential cross-section.
OPEN DESCENDANTS OF NAHE-BASED FREE FERMIONIC AND TYPE I ${\mathbb Z}_2^n$ MODELS
Authors: CLEMENTS DAVID J. , FARAGGI ALON E.
Published: August 2004

The NAHE set, that underlies the realistic free fermionic models, corresponds to ℤ2×ℤ2 orbifold at an enhanced symmetry point, with (h11,h21)=(27,3). Alternatively, a manifold with the same data is obtained by starting with a ℤ2×ℤ2 orbifold at a generic point on the lattice and adding a freely acting ℤ2 involution. In this paper we study type I orientifolds on the manifolds that underlie the NAHE-based models by incorporating such freely acting shifts. We present new models in the type I vacuum which are modulated by [Formula: see text] for n=2,3. In the case of n=2, the ℤ2×ℤ2 structure is a composite orbifold Kaluza–Klein shift arrangement. The partition function provides a simpler spectrum with chiral matter. For n=3, the case discussed is a ℤ2 modulation of the T6/ℤ2×ℤ2 spectrum. The additional projection shows an enhanced closed and open sector with chiral matter. The brane stacks are correspondingly altered from those which are present in the ℤ2×ℤ2 orbifold. In addition, we discuss the models arising from the open sector with and without discrete torsion.
SCALE SYMMETRY BREAKING FROM THE DYNAMICS OF MAXIMAL RANK GAUGE FIELD STRENGTHS
Authors: GUENDELMAN E. I.
Published: August 2004

Scale invariant theories which contain maximal rank gauge field strengths (of D indices in D dimensions) are studied. The integration of the equations of motion of these gauge fields leads to the scale symmetry breaking of scale invariance. The cases in study are (i) the spontaneous generation of r-1 potentials in particle mechanics in a theory that contains only r-2 potentials in the scale invariant phase, (ii) mass generation in scalar field theories, (iii) generation of nontrivial dilaton potentials in generally covariant theories, and (iv) spontaneous generation of confining behavior in gauge theories. The possible origin of these models is discussed.
POTENTIALS OF ARBITRARY FORCES WITH FRACTIONAL DERIVATIVES
Authors: RABEI EQAB M. , ALHALHOLY TAREQ S. , ROUSAN AKRAM
Published: August 2004

The Laplace transform of fractional integrals and fractional derivatives is used to develop a general formula for determining the potentials of arbitrary forces: conservative and nonconservative in order to introduce dissipative effects (such as friction) into Lagrangian and Hamiltonian mechanics. The results are found to be in exact agreement with Riewe's results of special cases. Illustrative examples are given.
LIOUVILLE FIELD THEORY: A DECADE AFTER THE REVOLUTION
Authors: NAKAYAMA YU
Published: August 2004

We review recent developments (up to January 2004) of the Liouville field theory and its matrix model dual. This review consists of two parts. In part I, we review the bosonic Liouville theory. After briefly reviewing the necessary background, we discuss the bulk structure constants (the DOZZ formula) and the boundary states (the FZZT brane and the ZZ brane). Various applications are also presented. In part II, we review the supersymmetric extension of the Liouville theory. We first discuss the bulk structure constants and the branes as in the bosonic Liouville theory, and then we present the matrix dual descriptions with some applications. This review also includes some original material such as the derivation of the conjectured dual action for the [Formula: see text] Liouville theory from other known dualities.
A REDUCIBILITY PROBLEM FOR MONODROMY OF SOME SURFACE BUNDLES
Authors: IMAYOSHI YOICHI , ITO MANABU , YAMAMOTO HIROSHI
Published: August 2004

A surface bundle determines a monodromy representation recording the twisting of the fiber under transport around a closed path in the base space. The fascinating relation between these monodromy representations and the Thurston classification of surface automorphisms will be studied. In this note we deal with a simple and interesting case: the fibrations of Fadell and Neuwirth.
RESHETIKHIN–TURAEV INVARIANTS OF SEIFERT 3-MANIFOLDS FOR CLASSICAL SIMPLE LIE ALGEBRAS
Authors: HANSEN SØREN KOLD , TAKATA TOSHIE
Published: August 2004

We derive explicit formulas for the Reshetikhin–Turaev invariants of all oriented Seifert manifolds associated to an arbitrary complex finite dimensional simple Lie algebra [Formula: see text] in terms of the Seifert invariants and standard data for [Formula: see text]. A main corollary is a determination of the full asymptotic expansions of these invariants for lens spaces in the limit of large quantum level. This result is in agreement with the asymptotic expansion conjecture due to Andersen [1,2].
RIBBON-MOVES OF 2-LINKS PRESERVE THE μ-INVARIANT OF 2-LINKS
Authors: OGASA EIJI
Published: August 2004

We introduce ribbon-moves of 2-links, which are operations to make 2-links into new 2-links by local operations.

Let L1 and L2 be 2-links. Then the following hold.

(1) If L1 is ribbon-move equivalent to L2, then we have [Formula: see text] where μ( ) is the μ invariant of 2-links which is defined naturally by using the μ invariant of spin closed 3-manifolds.

(2) Suppose that L1 is ribbon-move equivalent to L2. Let Wi be arbitrary Seifert hypersurfaces for Li. Then the torsion part of H1(W1)⊕H1(W2) is isomorphic to G⊕G for a finite abelian group G.

(3) Not all 2-knots are ribbon-move equivalent to the trivial 2-knot.

(4) The converse of (1) is not true.

(5) The converse of (2) is not true.

Let L=(L1,L) be a sublink of homology boundary link. Then we have:

(i) L is ribbon-move equivalent to a boundary link.

(ii) μ(L)=μ(L1)+μ(L2).
PULL BACK RELATION FOR NON-SPHERICAL KNOTS
Authors: BLANLŒIL VINCENT , MATSUMOTO YUKIO , SAEKI OSAMU
Published: August 2004

We introduce a new relation for high dimensional non-spherical knots, which is motivated by the codimension two surgery theory: a knot is a pull back of another knot if the former is obtained as the inverse image of the latter by a certain degree one map between the ambient spheres. We show that this relation defines a partial order for (2n-1)-dimensional simple fibered knots for n≥3. We also give some related results concerning cobordisms and isotopies of knots together with several important explicit examples.
BRANCHED COVERINGS OF S3 AND VOLUME ZERO KNOTS
Authors: RAMIREZ-LOSADA ENRIQUE
Published: August 2004

We prove that the 3-sphere is a covering of itself branched over any volume zero knot.
SKEIN MODULES AT THE 4TH ROOTS OF UNITY
Authors: SIKORA ADAM S.
Published: August 2004

The Kauffman bracket skein modules, [Formula: see text], have been calculated for A=±1 for all 3-manifolds M by relating them to the [Formula: see text]-character varieties. We extend this description to the case when A is a 4th root of 1 and M is either a surface×[0,1] or a rational homology sphere (or its submanifold).
OPEN PROBLEMS IN USING AGENT-BASED MODELS IN INDUSTRIAL AND LABOR DYNAMICS
Authors: GILBERT NIGEL
Published: August 2004

The preceding papers have shown the impressive versatility and potential of agent-based modeling in developing an understanding of industrial and labor dynamics. The main attraction of agent-based models is that the actors — firms, workers, and networks — that are the objects of study in the 'real world,' can be represented directly in the model. This one-to-one correspondence between model agents and economic actors provides greater clarity and more opportunities for analysis than many alternative modeling approaches. However, the advantages of agent-based modeling have to be tempered by disadvantages and as yet unsolved methodological problems. In this brief summary drawn from the discussion at the closing session of WILD@ACE, we review three of these open problems in the context of the papers presented at the conference: How can agent-based models be empirically validated? What criteria should be used to evaluate the explanatory success of agent-based models? And how can the conclusions of research on similar topics be integrated?
ECONOMICS AND COMPLEXITY
Authors: KIRMAN ALAN
Published: August 2004

This paper presents a view of the economy as a complex system with heterogeneous interacting agents who collectively organize themselves to generate aggregate phenomena which cannot be regarded as the behavior of some average or representative individual. There is an essential difference between the aggregate and the individual and such phenomena as bubbles and crashes, herd behavior, the transmission of information and the organization of trade are better modeled in the sort of framework suggested here than in more standard economic models.
MATCHING, BARGAINING, AND WAGE SETTING IN AN EVOLUTIONARY MODEL OF LABOR MARKET AND OUTPUT DYNAMICS
Authors: FAGIOLO G. , DOSI G. , GABRIELE R.
Published: August 2004

In this paper, we present an agent-based, evolutionary, model of output- and labor-market dynamics. Firms produce a homogeneous, perishable good under constant returns to scale using labor only. Labor productivities are firm-specific and change stochastically due to technical progress. The key feature of the model resides in an explicit microfoundation of the processes of : (i) matching between firms and workers, (ii) job search, (iii) wage setting, (iv) endogenous formation of aggregate demand, and (v) endogenous price formation. Moreover, we allow for a competitive process entailing selection of firms on the basis of their revealed competitiveness. Simulations show that the model is able to robustly reproduce Beveridge, Wage and Okun curves under quite broad behavioral and institutional settings. The system generates endogenously an Okun coefficient greater than one even if individual firms employ production functions exhibiting constant returns to labor. Monte Carlo simulations also indicate that statistically detectable shifts in Okun and Beveridge curves emerge as the result of changes in institutional, behavioral, and technological parameters. Finally, the model generates sharp predictions about how system parameters affect aggregate performance (i.e. average GDP growth) and its volatility.
ENDOGENOUS MATCHING FUNCTIONS: AN AGENT-BASED COMPUTATIONAL APPROACH
Authors: NEUGART MICHAEL
Published: August 2004

The matching function has become a popular tool in labor economics. It relates job creation (a flow variable) to two stock variables: vacancies and job searchers. In most studies the matching function is considered to be exogenous and assumed to have certain properties. The present study, instead, looks at the properties of an endogenous matching function. For this purpose we have programmed an agent-based computational labor market model with endogenous job creation and endogenous job search behavior. Our~simulations suggest that the endogenous matching technology is subject to decreasing returns to scale. The Beveridge curve reveals substitutability of job searchers and vacancies for a small range of inputs, but is flat for relatively high numbers of job searchers and vertical for relatively high numbers of vacancies. Moreover, the matching technology changes with labor market policies. This raises concerns about the validity of labor market policy evaluations conducted with flow models of the labor market that employ exogenous matching functions.
A FINITARY CHARACTERIZATION OF THE EWENS SAMPLING FORMULA
Authors: GARIBALDI U. , COSTANTINI D. , VIARENGO P.
Published: August 2004

The clustering of agents in the market is a typical problem dealt with in recent approaches to macroeconomic modeling, describing macroscopic variables in terms of the behavior of a large collection of microeconomic entities. Clustering is subject to many economic interpretations, often described by the Ewens Sampling Formula (ESF). In contrast with the usual complex derivations, we suggest a finitary characterization of the ESF pointing to real economic processes. Our approach is finitary in the sense that we provide a probabilistic description of a system of n individuals considered as a closed system, a population, where individuals can change attributes over time. The probability is understood as the fraction of time the system spends in the considered partition. As the ESF represents an equilibrium distribution satisfying detailed balance, some properties difficult to prove are derived in a simple way. Besides the mean distribution of the cluster sizes, we study the probabilistic time behavior of clusters, in particular the mean survival as a function of the actual size and the correlation between size and age.