bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolite Fingerprinting in Transgenic Nicotiana tabacum Altered by the Escherichia coli Glutamate Dehydrogenase Gene
Authors: Mungur R. , Glass A. D. M. , Goodenow D. B. , Lightfoot D. A.
Published: June 2005

With about 200 000 phytochemicals in existence, identifying those of biomedical significance is a mammoth task. In the postgenomic era, relating metabolite fingerprints, abundances, and profiles to genotype is also a large task. Ion analysis using Fourier transformed ion cyclotron resonance mass spectrometry (FT‐ICR‐MS) may provide a high‐throughput approach to measure genotype dependency of the inferred metabolome if reproducible techniques can be established. Ion profile inferred metabolite fingerprints are coproducts. We used FT‐ICR‐MS‐derived ion analysis to examine gdhA (glutamate dehydrogenase (GDH; EC 1.4.1.1)) transgenic Nicotiana tabacum (tobacco) carrying out altered glutamate, amino acid, and carbon metabolisms, that fundamentally alter plant productivity. Cause and effect between gdhA expression, glutamate metabolism, and plant phenotypes was analyzed by 13NH4+ labeling of amino acid fractions, and by FT‐ICR‐MS analysis of metabolites. The gdhA transgenic plants increased 13N labeling of glutamate and glutamine significantly. FT‐ICR‐MS detected 2 012 ions reproducible in 2 to 4 ionization protocols. There were 283 ions in roots and 98 ions in leaves that appeared to significantly change abundance due to the measured GDH activity. About 58% percent of ions could not be used to infer a corresponding metabolite. From the 42% of ions that inferred known metabolites we found that certain amino acids, organic acids, and sugars increased and some fatty acids decreased. The transgene caused increased ammonium assimilation and detectable ion variation. Thirty‐two compounds with biomedical significance were altered in abundance by GDH including 9 known carcinogens and 14 potential drugs. Therefore, the GDH transgene may lead to new uses for crops like tobacco.
Early‐Stage Folding in Proteins (In Silico) Sequence‐to‐Structure Relation
Authors: Brylinski Michał , Konieczny Leszek , Czerwonko Patryk , Jurkowski Wiktor , Roterman Irena
Published: June 2005

A sequence‐to‐structure library has been created based on the complete PDB database. The tetrapeptide was selected as a unit representing a well‐defined structural motif. Seven structural forms were introduced for structure classification. The early‐stage folding conformations were used as the objects for structure analysis and classification. The degree of determinability was estimated for the sequence‐to‐structure and structure‐to‐sequence relations. Probability calculus and informational entropy were applied for quantitative estimation of the mutual relation between them. The structural motifs representing different forms of loops and bends were found to
favor particular sequences in structure‐to‐sequence analysis.
Acute hepatic failure and multi-system organ failure secondary to replacement of the liver with metastatic melanoma
Authors: Kaplan Gilaad G , Medlicott Shaun , Culleton Bruce , Laupland Kevin B
Published: June 2005

Background

Metastatic malignant melanoma to the liver resulting in fulminant hepatic failure is a rare occurrence.

Case presentation

A 46 year old man presented to hospital with massive hepatomegaly, elevated liver enzymes and increased lactate three weeks following resection of a malignant melanoma from his shoulder (Clark level 5). Initially stable, he decompensated 24 to 48 hours subsequent to presentation with respiratory failure requiring mechanical ventilation, distributive shock requiring high dose vasopressor infusion, coagulopathy refractory to plasma infusion, progressive rise in liver enzymes and severe metabolic abnormalities including hyperkalemia, acidosis, hyperphosphatemia, hyperuricemia and hypocalcemia. Refractory to aggressive physiologic support he received palliation. Autopsy revealed >80% liver infiltration by metastatic malignant melanoma.

Conclusion

We report a case of fulminant hepatic failure secondary to metastatic malignant melanoma infiltration of the liver.
The impact of a pharmacist-managed dosage form conversion service on ciprofloxacin usage at a major Canadian teaching hospital: a pre- and post-intervention study
Authors: Ho Bradley P , Lau Tim TY , Balen Robert M , Naumann Terryn L , Jewesson Peter J
Published: June 2005

Background

Despite cost containment efforts, parenteral (IV) ciprofloxacin appears to be overutilized at Vancouver General Hospital. In November 2003, the Pharmacist-managed intravenous to oral (IV-PO) Dosage Form Conversion Service was implemented, enabling autonomous pharmacist-initiated dosage form conversion for ciprofloxacin. This study evaluates characteristics of ciprofloxacin use prior to and following implementation of this conversion service.

Methods

This was a single-centre, two-phase (pre/post), unblinded study. Phase I occurred between November 12, 2002 and November 11, 2003 (365 days), and Phase II between November 12, 2003 and March 11, 2004 (120 days). All patients receiving ciprofloxacin IV during these periods were reviewed. The primary endpoint was IV:PO ciprofloxacin use ratio. Secondary endpoints were total number of ciprofloxacin doses, proportion of inappropriate IV ciprofloxacin doses, cost of therapy between phases, and estimated cost avoidance with the intervention.

Results

Two hundred ciprofloxacin IV treatment courses were evaluated (100 per phase). The IV:PO ciprofloxacin use ratio was 3.03 (Phase I) vs. 3.48 (Phase II). Total number of doses and ratio of IV to total doses across phases were similar (p = 0.2830). IV-PO ciprofloxacin conversion occurred in 27/100 (27%) of IV courses in Phase I and 23/100 (23%) in Phase II. Proportion of inappropriate ciprofloxacin IV doses decreased between Phases I and II (244/521 (47%) vs. 201/554 (36%) (p = 0.0005), respectively). Furthermore, the proportion of pharmacist-preventable inappropriate ciprofloxacin IV doses was reduced between Phases I and II (114/244 (47%) vs. 65/201 (32%) (p = 0.0026). Proportional cost avoidance associated with total inappropriate IV use was $7,172/$16,517 (43%) (in Canadian dollars) in Phase I vs. $6,012/$17,919 (34%) in Phase II (p = 0.001). Similarly, proportional cost avoidance associated with pharmacist-preventable inappropriate IV doses was reduced from $3,367/$16,517 (20%) in Phase I to $1,975/$17,919 (11%) in Phase II (p = 0.001).

Conclusion

While overall utilization of ciprofloxacin remained unchanged and the proportion of IV to total doses was stable during the study period, the proportion of inappropriate IV doses and its associated costs appear to have declined subsequent to implementation of a Pharmacist-managed IV-PO Dosage Form Conversion Service. Such a program may be a beneficial adjunct in facilitating appropriate and cost-effective usage of ciprofloxacin.
The basophil activation test by flow cytometry: recent developments in clinical studies, standardization and emerging perspectives
Authors: Boumiza Radhia , Debard Anne-Lise , Monneret Guillaume
Published: June 2005

The diagnosis of immediate allergy is mainly based upon an evocative clinical history, positive skin tests (gold standard) and, if available, detection of specific IgE. In some complicated cases, functionalin vitrotests are necessary. The general concept of those tests is to mimicin vitrothe contact between allergens and circulating basophils. The first approach to basophil functional responses was the histamine release test but this has remained controversial due to insufficient sensitivity and specificity. During recent years an increasing number of studies have demonstrated that flow cytometry is a reliable tool for monitoring basophil activation upon allergen challenge by detecting surface expression of degranulation/activation markers (CD63 or CD203c). This article reviews the recent improvements to the basophil activation test made possible by flow cytometry, focusing on the use of anti-CRTH2/DP2antibodies for basophil recognition. On the basis of a new triple staining protocol, the basophil activation test has become a standardized tool forin vitrodiagnosis of immediate allergy. It is also suitable for pharmacological studies on non-purified human basophils. Multicenter studies are now required for its clinical assessment in large patient populations and to define the cut-off values for clinical decision-making.
The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects
Authors: Mager DL , Haffajee AD , Devlin PM , Norris CM , Posner MR , Goodson JM
Published: June 2005

Background

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.

Methods

Unstimulated saliva samples were collected from 229 OSCC-free and 45 OSCC subjects and evaluated for their content of 40 common oral bacteria using checkerboard DNA-DNA hybridization. DNA counts per ml saliva were determined for each species, averaged across subjects in the 2 subject groups, and significance of differences between groups determined using the Mann-Whitney test and adjusted for multiple comparisons. Diagnostic sensitivity and specificity in detection of OSCC by levels of salivary organisms were computed and comparisons made separately between a non-matched group of 45 OSCC subjects and 229 controls and a group of 45 OSCC subjects and 45 controls matched by age, gender and smoking history.

Results

Counts of 3 of the 40 species tested,Capnocytophaga gingivalis,Prevotella melaninogenicaandStreptococcus mitis, were elevated in the saliva of individuals with OSCC (p < 0.001). When tested as diagnostic markers the 3 species were found to predict 80% of cancer cases (sensitivity) while excluding 83% of controls (specificity) in the non-matched group. Diagnostic sensitivity and specificity in the matched group were 80% and 82% respectively.

Conclusion

High salivary counts ofC. gingivalis,P. melaninogenicaandS. mitismay be diagnostic indicators of OSCC.
Interventions to facilitate health workforce restructure
Authors: Duckett SJ
Published: June 2005

There are recognised shortages in most health professions in Australia. This is evidence that previous attempts at health workforce planning have failed. This paper argues that one reason for such failure is the lack of appropriate structures for health workforce planning. It also suggests that Australia needs to move beyond planning for particular professions and that health workforce planning needs to be based on identifying skill shortages as much as shortages in particular named professionals.

The paper proposes specific policy suggestions to facilitate workforce flexibility and health workforce planning in Australia.
Substance P-Driven Feed-Forward Inhibitory Activity in the Mammalian Spinal Cord
Authors: Nakatsuka Terumasa , Chen Meng , Takeda Daisuke , King Christopher , Ling Jennifer , Xing g , Ataka Toyofumi , Vierck Charles , Yezierski Robert , Gu Jianguo G
Published: June 2005

In mammals, somatosensory input activates feedback and feed-forward inhibitory circuits within the spinal cord dorsal horn to modulate sensory processing and thereby affecting sensory perception by the brain. Conventionally, feedback and feed-forward inhibitory activity evoked by somatosensory input to the dorsal horn is believed to be driven by glutamate, the principle excitatory neurotransmitter in primary afferent fibers. Substance P (SP), the prototypic neuropeptide released from primary afferent fibers to the dorsal horn, is regarded as a pain substance in the mammalian somatosensory system due to its action on nociceptive projection neurons. Here we report that endogenous SP drives a novel form of feed-forward inhibitory activity in the dorsal horn. The SP-driven feed-forward inhibitory activity is long-lasting and has a temporal phase distinct from glutamate-driven feed-forward inhibitory activity. Compromising SP-driven feed-forward inhibitory activity results in behavioral sensitization. Our findings reveal a fundamental role of SP in recruiting inhibitory activity for sensory processing, which may have important therapeutic implications in treating pathological pain conditions using SP receptors as targets.
Association between the TNFRII 196R allele and diagnosis of rheumatoid arthritis
Authors: Goëb Vincent , Dieudé Philippe , Vittecoq Olivier , Mejjad Othmane , Ménard Jean-François , Thomas Marlène , Gilbert Danièle , Boumier Patrick , Pouplin Sophie , Daragon Alain , Fardellone Patrice , Tron François , Cornélis François , Le Loët Xavier
Published: June 2005

Tumour necrosis factor (TNF)-α plays a key role in the pathogenesis of rheumatoid arthritis (RA). It binds to two receptors, namely TNF receptor (TNFR)I and TNFRII. Several studies have suggested an association between TNFRII 196R/R genotype and RA. The objective of the present study was to evaluate the predictive value of the TNFRII 196R allele for RA diagnosis and prognosis in a cohort of patients with very early arthritis. We followed up a total of 278 patients recruited from the community, who had swelling of at least two joints that had persisted for longer than 4 weeks but had been evolving for less than 6 months, and who had not received disease-modifying antirheumatic drugs or steroid therapy. At 2 years, patients were classified according to the American College of Rheumatology criteria. All patients were genotyped with respect to TNFRII 196M/R polymorphism. Radiographs of hands and feet (read according to the modified Sharp method) and the Health Assessment Questionnaire were used to quantify structural and functional severity. The cohort of 278 patients was found to include 156 and 122 RA and non-RA patients, respectively. The TNFRII 196R allele was found to be associated with RA (P = 0.002). However, progression of radiographic severity and Health Assessment Questionnaire scores over 1 year did not differ between carriers of the 196R allele and noncarriers. Our findings suggest that the TNFRII 196R allele may be associated with RA diagnosis but that it does not predict early radiographic progression or functional severity in patients with very early, unclassified arthritis.
Analysis of the Macaca mulatta transcriptome and the sequence divergence between Macaca and human
Authors: Magness Charles L , Fellin P Campion , Thomas Matthew J , Korth Marcus J , Agy Michael B , Proll Sean C , Fitzgibbon Matthew , Scherer Christina A , Miner Douglas G , Katze Michael G , Iadonato Shawn P
Published: June 2005

We report the initial sequencing and comparative analysis of the Macaca mulatta transcriptome. Cloned sequences from 11 tissues, nine animals, and three species (M. mulatta, M. fascicularis, and M. nemestrina) were sampled, resulting in the generation of 48,642 sequence reads. These data represent an initial sampling of the putative rhesus orthologs for 6,216 human genes. Mean nucleotide diversity within M. mulatta and sequence divergence among M. fascicularis, M. nemestrina, and M. mulatta are also reported.
Domestic violence and its mental health correlates in Indian women
Authors: Kumar Shuba , Jeyaseelan Lakshmanan , Suresh Saradha , Ahuja Ramesh Chandra
Published: June 2005

Background

Domestic spousal violence against women has far-reaching mental health implications.

Aims

To determine the association of domestic spousal violence with poor mental health.

Method

In a household survey of rural, urban non-slum and urban slum areas from seven sites in India, the population of women aged 15–49 years was sampled using probability proportionate to size. The Self Report Questionnaire was used to assess mental health status and a structured questionnaire elicited spousal experiences of violence.

Results

Of 9938 women surveyed, 40% reported poor mental health. Logistic regression showed that women reporting ‘any violence’ – ‘slap’, ‘hit’, ‘kick’ or ‘beat’ (OR 2.2, 95% CI 2.0–2.5) – or ‘all violence’ – all of the four types of physically violent behaviour (OR 3.5, 95% CI 2.94–3.51) – were at increased risk of poor mental health.

Conclusions

Findings indicate a strong association between domestic spousal violence and poor mental health, and underscore the need for appropriate interventions.
Persistence of Medical Change at Implementation of Clinical Guidelines on Medical Practice: A Controlled Study in a Cancer Network
Authors: Ray-Coquard Isabelle , Philip Thierry , de Laroche Guy , Froger Xavier , Suchaud Jean-Philippe , Voloch Alain , Mathieu-Daudé Hélène , Lurkin Antoine , Farsi Fadila , Bertrand Pierre , Chauvin Franck
Published: June 2005

Purpose

A cancer network of general or private hospitals of a French region was started in 1995 for improving quality of care and rationalizing medical prescriptions. The impact of implementing a clinical practice guidelines (CPG) project assessed conformity with guidelines in medical practice; significant changes were observed within the network, whereas no changes were observed in a control region without cancer network. In the present study, we evaluated the persistence of conformity to guidelines through a new medical audit.

Patients and Methods

In 1999, the hospitals of the previously compared experimental and control groups accepted to reassess the impact of CPG. A controlled transversal study was performed in the experimental group (cancer network) and in the control group (no regional cancer network). In 1996 (first audit) and in 1999 (present audit), all new patients with colon cancer (177 and 200 in experimental group and 118 and 100 in control group, respectively) and early breast cancer (444 and 381 in experimental group and 172 and 204 in control group, respectively) were selected.

Results

In the experimental group, the compliance of medical decisions with CPG was significantly higher in 1999 than in 1996 for colon cancer (73%; 95% CI, 67% to 79% v 56%; 95% CI, 49% to 63%, respectively; P = .003) and similar for the two periods for breast cancer (36%; 95% CI, 31% to 41% v 40%; 95% CI, 35% to 44%, respectively; P = .24). In the control group, compliance was significantly higher in 1999 than in 1996 for colon cancer (67%; 95% CI, 58% to 76% v 38%; 95% CI, 29% to 47%, respectively; P < .001) and identical for the two periods for breast cancer (4%; 95% CI, 1% to 7% v 7%; 95% CI, 3% to 11%, respectively; P = .19).

Conclusion

The CPG program for cancer management produced persistent changes in medical practice in our cancer network in terms of conformity with CPG.
Randomized Phase II Designs in Cancer Clinical Trials: Current Status and Future Directions
Authors: Lee J. Jack , Feng Lei
Published: June 2005

Purpose

Randomized phase II (RPh2) designs are popular in cancer clinical trials because of the smaller sample size requirements when multiple treatments are being evaluated. We reviewed the use of RPh2 designs and give comments on future directions.

Design

The trial design, statistical properties, conduct, data analysis, results, and reporting were examined in RPh2 trials reported from 1986 to 2002.

Results

A statistical design was reported in only 46% of the 266 cancer trials, and approximately half of those provided inadequate information. Most studies applied randomization to achieve patient comparability, while embedding a one-sample phase II design within each treatment arm. Seventy-five percent of the trials’ accruals were within ± 10% of their targets. The average accrual rate was 3.3 patients per month. Planned interim analyses were reported in 27% of the trials, and 56% of the trials were stopped early; 69%, 13%, 13%, and 4% of the trial discontinuations were because of lack of efficacy, efficacy, toxicity, and slow accrual, respectively. Thirty-nine trials (14%) recommended or started phase III evaluations, with four positive reports in six phase III studies identified.

Conclusion

There is a trend of increasing use of RPh2 designs in cancer research. Continued improvement in study design, conduct, analysis, and reporting is required to enhance the quality of RPh2 designs. The accrual rate and success rate of the trials remain low, and therefore, futility stopping rules to terminate ineffective treatment arm(s) should be implemented more frequently. More innovative, flexible RPh2 designs are needed to facilitate the development of effective cancer treatments.
Morbidity After Sentinel Lymph Node Biopsy in Primary Breast Cancer: Results From a Randomized Controlled Trial
Authors: Purushotham Anand David , Upponi Sara , Klevesath Manfred Borislav , Bobrow Lynda , Millar Keith , Myles Jonathan Peter , Duffy Stephen William
Published: June 2005

Purpose

Axillary lymph node dissection (ALND) as part of surgical treatment for patients with breast cancer is associated with significant morbidity. Sentinel lymph node biopsy (SLNB) is a newly developed method of staging the axilla and has the potential to avoid an ALND in lymph node–negative patients, thereby minimizing morbidity. The aim of this study was to investigate physical and psychological morbidity after SLNB in the treatment of early breast cancer in a randomized controlled trial.

Patients and Methods

Between November 1999 and February 2003, 298 patients with early breast cancer (tumors 3 cm or less on ultrasound examination) who were clinically node negative were randomly allocated to undergo ALND (control group) or SLNB followed by ALND if subsequently found to be lymph node positive (study group). A detailed assessment of physical and psychological morbidity was performed during a 1-year period postoperatively.

Results

A significant reduction in postoperative arm swelling, rate of seroma formation, numbness, loss of sensitivity to light touch and pinprick was observed in the study group. Although shoulder mobility was less impaired on average in the study group, this was significant only for abduction at 1 month and flexion at 3 months. Scores reflecting quality of life and psychological morbidity were significantly better in the study group in the immediate postoperative period, with fewer long-term differences.

Conclusion

SLNB in patients undergoing surgery for breast cancer results in a significant reduction in physical and psychological morbidity.
Comparison of HER2 Status by Fluorescence in Situ Hybridization and Immunohistochemistry to Predict Benefit From Dose Escalation of Adjuvant Doxorubicin-Based Therapy in Node-Positive Breast Cancer Patients
Authors: Dressler Lynn G. , Berry Donald A. , Broadwater Gloria , Cowan David , Cox Kelly , Griffin Stephanie , Miller Ashley , Tse Jessica , Novotny Debra , Persons Diane L. , Barcos Maurice , Henderson I. Craig , Liu Edison T. , Thor Ann , Budman Dan , Muss Hy , Norton Larry , Hayes Daniel F.
Published: June 2005

Purpose

HER2 is a clinically important tumor marker in breast cancer; however, there is controversy regarding which method reliably measures HER2 status. We compared three HER2 laboratory methods: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR), to predict disease-free survival (DFS) and overall survival (OS) after adjuvant doxorubicin-based therapy in node-positive breast cancer patients.

Methods

This is a Cancer and Leukemia Group B (CALGB) study, using 524 tumor blocks collected from breast cancer patients registered to clinical trial CALGB 8541. IHC employed CB11 and AO-11-854 monoclonal antibodies; FISH used PathVysion HER2 DNA Probe kit; PCR utilized differential PCR (D-PCR) methodology.

Results

Cases HER2 positive by IHC, FISH and D-PCR were 24%, 17%, and 18%, respectively. FISH and IHC were clearly related (κ = 64.8%). All three methods demonstrated a similar relationship for DFS and OS. By any method, for patients with HER2-negative tumors, there was little or no effect of dose of adjuvant doxorubicin-based therapy. For patients with HER2-positive tumors, all three methods predicted a benefit from dose-intense (high-dose) compared with low- or moderate-dose adjuvant doxorubicin-based therapy.

Conclusion

FISH is a reliable method to predict clinical outcome following adjuvant doxorubicin-based therapy for stage II breast cancer patients. There is a moderate level of concordance among the three methods (IHC, FISH, PCR). None of the methods is clearly superior. Although IHC-positive/FISH-positive tumors yielded the greatest interaction with dose of therapy in predicting outcome, no combination of assays tested was statistically superior.
Multicenter Study of a Frozen Glove to Prevent Docetaxel-Induced Onycholysis and Cutaneous Toxicity of the Hand
Authors: Scotté Florian , Tourani Jean-Marc , Banu Eugeniu , Peyromaure Michel , Levy Eric , Marsan Sandrine , Magherini Emmanuelle , Fabre-Guillevin Elisabeth , Andrieu Jean-Marie , Oudard Stéphane
Published: June 2005

Purpose

Onycholysis and skin toxicity occur in approximately 30% of patients treated with docetaxel. We investigated the efficacy and safety of an Elasto-Gel (84400 APT Cedex, Akromed, France) frozen glove (FG) for the prevention of docetaxel-induced onycholysis and skin toxicity.

Patients and Methods

Patients receiving docetaxel 75 mg/m2 alone or in combination chemotherapy were eligible for this case-control study. Each patient wore an FG for a total of 90 minutes on the right hand. The left hand was not protected and acted as the control. Onycholysis and skin toxicity were assessed at each cycle by National Cancer Institute Common Toxicity Criteria and documented by photography. Wilcoxon matched-pairs rank test was used.

Results

Between August 2002 and September 2003, 45 patients were evaluated. Onycholysis and skin toxicity were significantly lower in the FG-protected hand compared with the control hand (P = .0001). Onycholysis was grade (G) 0 in 89% v 49% and G1 to 2 in 11% v 51% for the FG-protected hand and the control hand, respectively. Skin toxicity was G0 in 73% v 41% and G1 to 2 in 27% v 59% for the FG-protected and the control hand, respectively. Median time to nail and skin toxicity occurrence was not significantly different between the FG-protected and the control hand, respectively (106 v 58 days for nail toxicity; 57 v 58 days for skin toxicity). Five patients (11%) experienced discomfort due to cold intolerance.

Conclusion

FG significantly reduces the nail and skin toxicity associated with docetaxel and provides a new tool in supportive care management to improve a patient's quality of life.
DrosophilaWntD is a target and an inhibitor of the Dorsal/Twist/Snail network in the gastrulating embryo
Authors: Ganguly Atish , Jiang Jin , Ip Y. Tony
Published: June 2005

The maternal Toll signaling pathway sets up a nuclear gradient of the transcription factor Dorsal in the early Drosophila embryo. Dorsal activates twist and snail, and the Dorsal/Twist/Snail network activates and represses other zygotic genes to form the correct expression patterns along the dorsoventral axis. An essential function of this patterning is to promote ventral cell invagination during mesoderm formation,but how the downstream genes regulate ventral invagination is not known. We show here that wntD is a novel member of the Wnt family. The expression of wntD is activated by Dorsal and Twist, but the expression is much reduced in the ventral cells through repression by Snail. Overexpression of WntD in the early embryo inhibits ventral invagination,suggesting that the de-repressed WntD in snail mutant embryos may contribute to inhibiting ventral invagination. The overexpressed WntD inhibits invagination by antagonizing Dorsal nuclear localization, as well as twist and snail expression. Consistent with the early expression of WntD at the poles in wild-type embryos, loss of WntD leads to posterior expansion of nuclear Dorsal and snail expression,demonstrating that physiological levels of WntD can also attenuate Dorsal nuclear localization. We also show that the de-repressed WntD in snail mutant embryos contributes to the premature loss of snail expression, probably by inhibiting Dorsal. Thus, these results together demonstrate that WntD is regulated by the Dorsal/Twist/Snail network,and is an inhibitor of Dorsal nuclear localization and function.
Hypoxia-inducible factor-dependent histone deacetylase activity determines stem cell fate in the placenta
Authors: Maltepe Emin , Krampitz Geoffrey W. , Okazaki Kelly M. , Red-Horse Kristy , Mak Winifred , Simon M. Celeste , Fisher Susan J.
Published: June 2005

Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor composed of HIFα and the arylhydrocarbon receptor nuclear translocator(ARNT/HIF1β). Previously, we have reported that ARNT function is required for murine placental development. Here, we used cultured trophoblast stem (TS)cells to investigate the molecular basis of this requirement. In vitro, wild-type TS cell differentiation is largely restricted to spongiotrophoblasts and giant cells. Interestingly, Arnt-null TS cells differentiated into chorionic trophoblasts and syncytiotrophoblasts, as demonstrated by their expression of Tfeb, glial cells missing 1 (Gcm1) and the HIV receptor CXCR4. During this process, a region of the differentiating Arnt-null TS cells underwent granzyme B-mediated apoptosis,suggesting a role for this pathway in murine syncytiotrophoblast turnover. Surprisingly, HIF1α and HIF2α were induced during TS cell differentiation in 20% O2; additionally, pVHL levels were modulated during the same time period. These results suggest that oxygen-independent HIF functions are crucial to this differentiation process. As histone deacetylase(HDAC) activity has been linked to HIF-dependent gene expression, we investigated whether ARNT deficiency affects this epigenetic regulator. Interestingly, Arnt-null TS cells had reduced HDAC activity,increased global histone acetylation, and altered class II HDAC subcellular localization. In wild-type TS cells, inhibition of HDAC activity recapitulated the Arnt-null phenotype, suggesting that crosstalk between the HIFs and the HDACs is required for normal trophoblast differentiation. Thus, the HIFs play important roles in modulating the developmental plasticity of stem cells by integrating physiological, transcriptional and epigenetic inputs.
Improved blocking properties of short‐chain alkanethiol monolayers self‐assembled on gold
Authors: Wanunu Meni , Vaskevich Alexander , Rubinstein Israel
Published: June 2005

Blocking of gold surfaces by self‐assembled monolayers (SAMs) of n‐octanethiol (OT) was investigated. Short‐chain alkanethiols such as OT are known to form loosely‐packed SAMs with abundant defects and pinholes, exhibiting poor blocking of the gold surface. Hence, gold substrates subjected to 20 h OT adsorption manifested excessive electrochemical penetrability, low contact angles with a large hysteresis, and extensive exchange of functional disulfide molecules into the OT SAM. It is shown that a single electrochemical cycle in H2SO4 solution after 1 h OT adsorption, followed by another 20 h adsorption, results in a dramatic improvement of the coverage and blocking properties of the SAM, showing considerably lower electrochemical penetrability, improved contact angles, and sluggish exchange of the functional molecules into the OT SAM. Insertion of the latter molecules into the monolayer was monitored by their ability to coordinatively attach ligand‐substituted gold nanoparticles.
X‐ray reflectivity study of cyclic peptide monolayers at the air‐water interface
Authors: Ahmad Farhan , Constabel Friederike , Geckeler Kurt E. , Seeck Oliver H. , Seo Young‐Soo , Satija Sushil K. , Kubik Stefan , Shin Kwanwoo
Published: June 2005

The dynamic and living characteristics of monolayers at the air‐water interface of a cyclohexapeptide (C6G) and a cyclooctapeptide (C8G), both composed of glutamic acid and 3‐aminobenzoic acid subunits in an alternating sequence, were investigated using the Langmuir balance technique, Brewster angle microscopy (BAM), and X‐ray reflectivity (XR). An alanine‐containing cyclohexapeptide (C6A) was included in this study for comparison. All three cyclopeptides preferentially adopt an orientation parallel to the subphase at low surface pressure. Continuous compression then causes the molecules to flip to a perpendicular state, thus minimizing their molecular area. In contrast to C8G and C6A, a pronounced hysteresis observed during the compression‐expansion cycle of C6G indicates that strong intermolecular interactions between the cyclopeptide rings occur in the monolayers of this peptide. This result is supported by BAM measurements that show the formation of crystallite structures for C6G at high surface pressures, whereas no structures were observed for C8G and C6A. These results indicate that C6G is able to self‐assemble upon surface compression, an ability that is obviously critically dependent on the correct ring size and composition of the peptide. The presence of hydrogen bond acceptors in the side chains of C6G suggests that the structural stabilization of the monolayer is due to H‐bonding, possibly between ring NH groups and side chain CO groups. Our in situ study thus provides a detailed understanding of the molecular dynamics and uninterrupted interfacial behavior of the three peptides in a real‐time frame.
Self‐assembly of peptide nanotubes and amyloid‐like structures by charged‐termini‐capped diphenylalanine peptide analogues
Authors: Reches Meital , Gazit Ehud
Published: June 2005

We had recently demonstrated that the diphenylalanine peptide, the core recognition motif of the Alzheimer's ß‐amyloid polypeptide, self‐assembles into a novel class of peptide nanotubes. The formation of well‐ordered supramolecular structures at the nanoscale by such a simple peptide was consistent with our suggestion that aromatic interactions may provide order and directionality needed for the formation of fibrillar peptide structures. Yet, we could not rule out a contribution of the charged amine and carboxyl moieties at the termini of the short peptide. In order to explore the potential role of electrostatic interaction in the assembly process we have studied a modified non‐charged peptide analogue, Ac‐Phe–Phe‐NH2, in which the N‐terminal amine was acetylated and the C‐terminal carboxyl was amidated. Scanning and transmission electron microscopy analyses demonstrated that this peptide analogue self‐assembles into highly‐ordered tubular structures, as observed with the NH2‐Phe–Phe‐COOH. Also, infrared spectroscopy revealed an amide I absorbance pattern that is very similar to that of the non‐modified peptide. Furthermore, an amidated NH2‐Phe–Phe‐NH2 peptide, which has a net positive charge, also self‐assembled into ordered tubular structures. On the other hand, the amine‐modified analogues Boc‐Phe–Phe‐COOH, Z‐Phe–Phe‐COOH, and Fmoc‐Phe–Phe‐COOH peptides formed amyloid‐like structures that had a significantly smaller diameter. Taken together, the current study further supports our hypothesis regarding the role of aromatic interactions in the self‐assembly of amyloid fibrils and amyloid‐associated nanostructures that can be modulated by simple chemical modifications.
Templated self‐assembly of porphyrin cages
Authors: Elemans Johannes A. A. W. , Slagt Vincent F. , Rowan Alan E. , Nolte Roeland J. M.
Published: June 2005

The development of self‐assembling catalysts, although an often‐tried approach, has achieved little success so far. Toward the construction of substrate selective catalysts, we have self‐assembled a porphyrin cage based upon the recognition of the templates meso‐dipyridyl (DPyP) or meso‐tetrapyridyl porphyrin (TPyP) by glycoluril‐based receptors that are functionalized with two pendant zinc porphyrins.
Multivalent aggregation of cyclodextrin gold nanoparticles and adamantyl‐terminated guest molecules
Authors: Crespo‐Biel Olga , Jukovic Amela , Karlsson Maria , Reinhoudt David N. , Huskens Jurriaan
Published: June 2005

The formation of large network aggregates composed of gold nanoparticles bearing surface‐immobilizedß‐cyclodextrin (CD) hosts whose assembly is driven by adamantyl‐terminated guest molecules was studied as a function of the number of interactions and the geometry of the guest molecules. The assembly was shown to be strong, specific, and irreversible by addition of an adamantyl‐terminated dendrimer leading to strong aggregation of the CD–Au nanoparticles and consequently to the formation of an insoluble precipitate. The bis‐adamantane guest molecule 3 allowed more control over the self‐assembly of such aggregates. Intramolecular interactions (at the same particle) were favored in this case over the intermolecular interactions (between particles), and the aggregation process of this guest could be inhibited by a monovalent competitor in solution.
Fullerene‐ and porphyrin‐appended crown ethers: Synthesis and preparation of stable langmuir and langmuir‐blodgett films
Authors: Marotti Federica , Bonifazi Davide , Gehrig Regula , Gallani Jean‐Louis , Diederich FrançOis
Published: June 2005

The synthesis of a series (1–5) of fullerene and Zn(II)‐porphyrin amphiphiles with polar dibenzo[24]crown‐8 headgroups is described. Their ability to form Langmuir monolayers at the air‐water interface was investigated in a systematic study. The Langmuir films were characterized by their surface pressure versus molecular area isotherms, compression and expansion cycles, and Brewsterangle microscopy. Complexation of larger alkali metal cations (K+ and Cs+) by the polar headgroups leads to higher molecular area requirements and a better anchoring to the aqueous subphase. The monolayers of the porphyrin‐(dibenzo[24]crown‐8) conjugates were transferred as Langmuir—Blodgett films onto glass slides and the films characterized by UV‐vis spectroscopy and grazing‐incidence X‐ray diffraction. Good evidence was obtained that the porphyrin‐fullerene‐crown ether triad 5 adopts a sandwich geometry in the LB films. In such an arrangement, the electron‐attracting carbon sphere benefits from attractive interactions with the sandwiching electron‐rich porphyrin and crown ether chromophores. The described films could have potential applications as functional materials in optical and electronic technology.
Calculation of soret‐shifted dew points by continuous mixture thermodynamics
Authors: Rosner Daniel E. , Arias‐Zugasti Manuel , LaMantia Barbara
Published: June 2005

Soret‐induced local concentration changes, very large numbers of condensable species, and condensate nonideality combine to make the calculation of isobaric dew‐point surface temperatures, Tdp, and corresponding incipient condensate compositions (xi, i = 1, 2, …, N) nontrivial, even with advanced computational methods. As usual in the canonical isobaric “dew‐point ” situation, the mainstream vapor mixture state [composition yi (i = 1, 2, …, N), T, and p] is fully specified. We consider here, for illustrative purposes, the tractable but frequently encountered limiting case of a very large number (perhaps dozens, if not hundreds) of condensable, nonreacting species that are members of a homologous series (such as n‐alkanes in a fuel “blend”), dilute in a “noncondensable ” carrier gas (such as N2). Pseudo‐binary Ludwig–Soret coefficients for the vapor phase are estimated from the corresponding Schmidt numbers and gas‐kinetic theory. As in our earlier studies (which emphasized binary “regular ” solutions of alkali sulfates), of particular current interest is the extent of systematic Soret‐induced shifts in the predicted dew‐point (wall) temperature and associated condensate composition/properties (such as viscosity). This often‐overlooked feature removes the present class of univariate problems from the province of classical continuous thermodynamics. Three efficient continuous mixture theory (CMT)–based computational methods are proposed/illustrated/compared, two moment‐based, and all exploiting Gaussian quadratures. We find that accurate results can be obtained while avoiding prescribing the shape of the distribution function in the condensate, using as few as three to four rationally selected “pseudo‐components.” © 2005 American Institute of Chemical Engineers AIChE J, 2005
Pregabalin‐withdrawal encephalopathy and splenial edema: A link to high‐altitude illness?
Authors: Oaklander Anne Louise , Buchbinder Bradley R.
Published: June 2005

A postherpetic‐neuralgia patient abruptly discontinued pregabalin. Thirty hours later, unexplained nausea, headache, and ataxia developed, progressing to delirium 8 days later. Magnetic resonance imaging indicated T2‐hyperintense lesions of her splenium. Similar magnetic resonance imaging abnormalities, interpreted as focal vasogenic edema, develop in some epileptic patients after rapid anticonvulsant withdrawal. Patients with high‐altitude cerebral edema have similar splenial‐predominant magnetic resonance imaging abnormalities that accompany these same neurological symptoms. This case is the first to associate anticonvulsant‐withdrawal splenial abnormalities with neurological symptoms, with gabapentin‐type anticonvulsants, and is among the first in nonepileptic patients, suggesting that sudden anticonvulsant withdrawal alone, unaccompanied by seizures, can initiate symptomatic focal brain edema. The similarity of this syndrome to high‐altitude cerebral edema suggests a possible common pathophysiology and offers potential therapies. Ann Neurol 2005
Palladiumkatalysierte Kreuzkupplungen in der Totalsynthese
Authors: Nicolaou K. C. , Bulger Paul G. , Sarlah David
Published: June 2005

Wenn man die Entwicklung der organischen Chemie betrachtet, kommt man schnell zu dem Schluss, dass kein Reaktionstyp dieses Gebiet in vergleichbarer Weise geprägt hat wie die Kohlenstoff‐Kohlenstoff‐Kupplungen. Grignard‐, Diels‐Alder‐ und Wittig‐Reaktionen sind nur drei herausragende Beispiele für solche Prozesse, die im vergangenen Jahrhundert zweifellos entscheidend am Aufstieg der chemischen Synthese beteiligt waren. Im letzten Viertel des 20. Jahrhunderts bereicherte eine neue Familie von leistungsfähigen Reaktionen zur Knüpfung von Kohlenstoff‐Kohlenstoff‐Bindungen das Repertoire der Synthesechemie: die übergangsmetallkatalysierten Reaktionen, allen voran die palladiumkatalysierten Kreuzkupplungen. In diesem Aufsatz werden Auszüge aus einer Reihe von ausgewählten Synthesen diskutiert. Die Beispiele sollen die enorme Leistungsfähigkeit dieser Prozesse in der Kunst der Totalsynthese aufzeigen und ihr Potenzial für zukünftige chemische Synthesen unterstreichen.
Palladium‐Catalyzed Cross‐Coupling Reactions in Total Synthesis
Authors: Nicolaou K. C. , Bulger Paul G. , Sarlah David
Published: June 2005

In studying the evolution of organic chemistry and grasping its essence, one comes quickly to the conclusion that no other type of reaction plays as large a role in shaping this domain of science than carbon–carbon bond‐forming reactions. The Grignard, Diels–Alder, and Wittig reactions are but three prominent examples of such processes, and are among those which have undeniably exercised decisive roles in the last century in the emergence of chemical synthesis as we know it today. In the last quarter of the 20th century, a new family of carbon–carbon bond‐forming reactions based on transition‐metal catalysts evolved as powerful tools in synthesis. Among them, the palladium‐catalyzed cross‐coupling reactions are the most prominent. In this Review, highlights of a number of selected syntheses are discussed. The examples chosen demonstrate the enormous power of these processes in the art of total synthesis and underscore their future potential in chemical synthesis.
ONTOWEB: Implementing an ontology‐based Web retrieval system
Authors: Kim Hyun Hee
Published: June 2005

The design and implementation of an ontology‐based Web retrieval (ONTOWEB) system is described; ONTOWEB allows the semantic search of the Web resources of international organizations such as the World Bank and the Organisation for Economic Co‐operation and Development (OECD). A firm's knowledge management project is introduced first, followed by a description of the ONTOWEB system's design, implementation, and evaluation. The ONTOWEB system has two components: databases and an ontology‐based search engine. The ontology‐based search engine is a tool used to query the information that has been loaded into the database. Last, to evaluate the system, an experiment was conducted to compare the performance of the proposed system with that of Internet search engines in terms of relevance and search time. This study shows that ontologies can be used not only to improve precision, but also to reduce the search time. Because of the expense of annotating resources, the domains that contain the most valuable knowledge, such as the medical and the business sectors, are prime areas for future ontology applications.
Computational intelligence to model the export behavior of multinational corporation subsidiaries in Malaysia
Authors: Edwards Ron , Abraham Ajith , Petrovic‐Lazarevic Sonja
Published: June 2005

The academic literature suggests that the extent of exporting by multinational corporation subsidiaries (MCSs) depends on their strategic role in the multinational corporation (MNC), their age and size, and whether their products are targeted at niche or commodity markets. In particular, it is claimed that MNCs seek to invest in a particular country if its resources adopt a vertically integrated structure, if the country grants regional or global sales mandates to their subsidiaries, or if it has been established in a host market for a longer time and is thus more likely to promote subsidiary exports. Our aim in this article is to model the complex export pattern behavior of multinational corporation subsidiaries in Malaysia using a Takagi–Sugeno fuzzy inference system. The proposed fuzzy inference system (FIS) is optimized by using neural network learning and evolutionary computation. Empirical results clearly show that the proposed approach could model the export behavior reasonably well compared to a direct neural network approach.
Der UNIQA Tower
Authors: Schöppl Michael , Kropik Christian , Seidl Jürgen
Published: June 2005

Als stark expandierendes Unternehmen der Versicherungsbranche faßte UNIQA den Entschluß, in Wien ein zukunftsweisendes, nach den Grundsätzen der Ökologie ausgelegtes Hauptquartier mit modernen Arbeitsplätzen zu errichten. Als Standort bot sich die Fläche zwischen dem bestehenden Firmensitz in der Unteren Donaustraße und der Aspernbrückengasse an. Im März 2000 wurden aus den Entwürfen der acht geladenen Architektenteams die Projekte von Dietmar Feichtinger und Heinz Neumann an die erste Stelle gereiht. Nach einer zweiten Präsentation stand im April 2000 fest, daß Heinz Neumanns elliptischer Baukörper, der das Firmenlogo des Konzerns optisch zur Geltung bringt, das neue Hauptquartier von UNIQA wird. Der UNIQA Tower stellt einen visuellen Schwerpunkt als markantes Wahrzeichen der Donaukanal‐Silhouette dar und ist zudem einer der wenigen Hochhaustürme in unmittelbarer Nähe zum Wiener Stadtkern. An diesem städtebaulich sensiblen Platz war seitens der Architektur die offene Struktur speziell in der Lobby, die bewußt als öffentlicher Raum konzipiert wurde, vorgegeben.