bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of vitamin C supplementation on serum concentrations of uric acid: Results of a randomized controlled trial
Authors: Huang Han‐Yao , Appel Lawrence J. , Choi Michael J. , Gelber Allan C. , Charleston Jeanne , Norkus Edward P. , Miller Edgar R.
Published: June 2005

Objective

Reductions in serum uric acid levels are clinically relevant. Previous studies have suggested a uricosuric effect of vitamin C. Whether vitamin C reduces serum uric acid is unknown. We undertook this study to determine the effects of vitamin C supplementation on serum uric acid concentrations.

Methods

The study was a double‐blinded placebo‐controlled randomized trial conducted in research units affiliated with an academic institution. Study participants were 184 nonsmokers, randomized to take either placebo or vitamin C supplements (500 mg/day) for 2 months.

Results

At the end of the study period, serum uric acid levels were significantly reduced in the vitamin C group (mean change −0.5 mg/dl [95% confidence interval −0.6, −0.3]), but not in the placebo group (mean change 0.09 mg/dl [95% confidence interval −0.05, 0.2]) (P < 0.0001). The same pattern of results was evident in subgroups defined by age, sex, race, body mass index, chronic illness, diuretic use, and quartiles of baseline serum ascorbic acid levels. In the subgroups, from the lowest to the highest quartile of baseline serum uric acid, net mean changes (95% confidence intervals) in serum uric acid with vitamin C supplementation were −0.4 (−0.8, 0.01), −0.5 (−0.9, −0.2), −0.5 (−0.8, −0.2), and −1.0 (−1.6, −0.4) mg/dl (P = 0.06, 0.005, 0.003, and 0.002, respectively). Compared with placebo, vitamin C increased the estimated glomerular filtration rate.

Conclusion

Supplementation with 500 mg/day of vitamin C for 2 months reduces serum uric acid, suggesting that vitamin C might be beneficial in the prevention and management of gout and other urate‐related diseases.
Violation of the intent‐to‐treat principle and rate of missing data in superiority trials assessing structural outcomes in rheumatic diseases
Authors: Baron Gabriel , Boutron Isabelle , Giraudeau Bruno , Ravaud Philippe
Published: June 2005

Objective

To evaluate the methodologic quality of and identify methodologic issues in superiority trials assessing structural outcomes in rheumatic diseases.

Methods

We searched Medline and the Cochrane Central Register of Controlled Trials for reports of randomized controlled trials assessing structural outcomes in osteoarthritis (OA), rheumatoid arthritis (RA), and osteoporosis (OP) published between January 1994 and December 2003 in high–impact factor general medical and specialty journals. One reader extracted data (quality assessment, intent‐to‐treat analysis [ITT analysis], rate of missing data, and methods of handling missing data), using a standardized form.

Results

A total of 81 reports were included in the analysis (37 on OP, 34 on RA, and 10 on OA). The mean ± SD methodologic quality scores on the Jadad scale (possible range 0–5) and the Delphi list (possible range 0–9) were 2.9 ± 1.2 and 6.4 ± 1.3, respectively. Although it was reported in 54 articles (66.7%) that the analysis was done on an ITT basis, full ITT analysis was performed in only 6 of the studies (7.4%), modified ITT analysis in 11 (13.6%), and case‐complete analysis in 48 (59.3%); the analysis was unclear in 16 articles (19.8%). The rate of missing data on structural outcomes could be determined in only 63 articles (77.8%) and was >20% in approximately one‐third of these reports. Methods for handling missing data on structural outcomes were described in 19 articles (23.5%) and were, in general, inappropriate.

Conclusion

Lack of ITT analysis and a high rate of missing data in superiority trials assessing structural outcomes may bias results from such trials. Our recommendations for improving these shortcomings may help researchers plan, analyze, and report the results of such trials.
Efficient and scalable method for scaling up cell free protein synthesis in batch mode
Authors: Voloshin Alexei M. , Swartz James R.
Published: June 2005

A novel method for general cell free system scale‐up in batch mode was applied to expression of E. coli chloramphenicol acetyl transferase (CAT) and a GMCSF‐scFv fusion protein being developed as a B‐cell lymphoma vaccine candidate (GLH). Performance of two different E. coli based cell‐free systems was evaluated using the new scale‐up approach. Reaction volumes from 15 to 500 µL were tested for both products and both reaction systems. In each case, the new scale‐up method preserved total, soluble, and active volumetric yields of GLH and CAT at every reaction volume. At the 500 µL reaction volume, the PANOx SP system produced 560 ± 36 µg/mL of active CAT and 99 ± 10 µg/mL of active GLH protein using the new thin film approach whereas 500 µL test tube reactions produced 250 ± 42 µg/mL and 72 ± 7 µg/mL of active CAT and GLH respectively. Similarly, 500 µL cell‐free synthesis reactions with the Cytomim system produced 481 ± 38 µg/mL of active CAT and 109 ± 15 µg/mL active GLH respectively in thin films compared to 29 ± 7 µg/mL of active CAT and 5 ± 2 µg/mL of active GLH protein in 500 µL test tube reactions. The new thin film approach improves oxygen supply for the Cytomim system, and increases the availability of hydrophobic surfaces. Analysis suggests that these surfaces provide significant benefit for protein expression and folding. We believe that this approach provides a general reaction scale‐up technology that will be suitable for any protein target, cell free system, and reaction volume. © 2005 Wiley Periodicals, Inc.
Process optimization of continuous gluconic acid fermentation by isolated yeast‐like strains of Aureobasidium pullulans
Authors: Anastassiadis Savas , Aivasidis Alexander , Wandrey Christian , Rehm Hans‐Jürgen
Published: June 2005

This study was focused on the optimization of a new fermentation process for continuous gluconic acid production by the isolated yeast‐like strain Aureobasidium pullulans DSM 7085 (isolate 70). Operational fermentation parameters were optimized in chemostat cultures, using a defined glucose medium. Different optima were found for growth and gluconic acid production for each set of operation parameters. Highest productivity was recorded at pH values between 6.5 and 7.0 and temperatures between 29 and 31°C. A gluconic acid concentration higher than 230 g/L was continuously produced at residence times of 12 h. A steady state extracellular gluconic acid concentration of 234 g/L was measured at pH 6.5. 122% air saturation yielded the highest volumetric productivity and product concentration. The biomass‐specific productivity increased steadily upon raising air saturation. An intracellular gluconic acid concentration of about 159 g/L (0.83 mol) was determined at 31°C. This is to be compared with an extracellular concentration of 223 g/L (1.16 mol), which indicates the possible existence of an active transport system for gluconic acid secretion, or the presence of extracellular glucose oxidizing enzymes. The new process provides significant advantages over the traditional discontinuous fungi operations. The process control becomes easier, thus offering stable product quality and quantity. © 2005 Wiley Periodicals, Inc.
Konzepte zur Grundwasserreinigung
Authors: Kopinke F.‐D. , Mackenzie K. , Köhler R. , Georgi A. , Roland U. , Weiß H.
Published: June 2005

Die Kontamination von Grundwasserleitern ist, anders als die Verschmutzung von Oberflächengewässern, für die meisten Menschen nicht wahrnehmbar. Dieser Umstand führt allerdings, zumindest in Deutschland, nicht zu einem verminderten Problembewusstsein, weil Trink‐ und Grundwasser im öffentlichen Bewusstsein eng miteinander verbunden sind. Die Sanierung von eingetretenen Grundwasserschäden zielt generell auf ein vernachlässigbar geringes oder tolerierbares Restrisiko für Schutzgüter. Sanierungsziele sollten immer unter Berücksichtigung der Angemessenheit des Aufwandes und der Umweltbilanz von Sanierungsmaßnahmen festgelegt werden. Ansonsten läuft man Gefahr, dass technischer Umweltschutz gut gemeint, aber letztlich gegen die Umwelt gerichtet ist. Dieser Beitrag befasst sich mit dem Selbstreinigungspotenzial kontaminierter Grundwasserleiter, behandelt passive Reinigungswände sowie aktive Sanierungsverfahren.
Verfahrenstechnische Möglichkeiten zur Verringerung des Anstiegs von Kohlendioxid in der Luft
Authors: Arlt W.
Published: June 2005

Der Beitrag beschäftigt sich mit verfahrenstechnischen Möglichkeiten der Begrenzung des Kohlendioxid‐Anteils in der Luft. Als Beispiel werden fossil befeuerte Kraftwerke betrachtet. Dazu werden zuerst die Stoffbilanzen erarbeitet. Es zeigt sich, dass die Ozeane für die Speicherung von Kohlendioxid die überragende Rolle spielen. Das eigentliche Problem ist jedoch nicht der Absolutgehalt an CO2, sondern die Veränderung des Wertes. Daraus wird abgeleitet, dass Erfolg versprechende Strategien das Kohlendioxid speichern sollten, um es später – in einigen hundert Jahren – wieder freisetzen zu können („verstecken“). Weltweite Sparmaßnahmen zum Erzielen des gleichen Effektes werden für nicht wahrscheinlich erachtet. In einer Übersicht werden literaturbekannte Kraftwerkskonzepte, Abtrenn‐ und Speicherverfahren vorgestellt. Ein Vorschlag sieht die Einleitung von Kohlendioxid in besonderen Flachwasserregionen vor. In diesen Regionen sinken gewaltige Wassermassen in die Tiefen des Ozeans ab und nähmen das gelöste Kohlendioxid auf eine mehrere hundert Jahre lange Reise mit. Es zeigt sich, dass die technischen Möglichkeiten bereits prinzipiell vorhanden sind. Mögliche Folgeszenarien, auch in Bezug auf die Ökologie, werden diskutiert und der sich ergebende Forschungsaufwand skizziert. Die sehr geringen europäischen Aktivitäten werden mit denjenigen Japans und der USA verglichen.
Entwicklung eines Dosierkonzeptes für kleinste Volumenströme
Authors: Kießlich F. , Prechtl P.M. , Gerhard H. , Liauw M.A. , Popovska N. , Emig G.
Published: June 2005

No abstracts.
Verweilzeitverteilung in Granulationstrommeln am Beispiel von Industrieruß
Authors: Katzer M. , Pirl S. , Esser S. , Kopietz J. , Rieckmann T. , Behnisch J. , Klasen C.‐J.
Published: June 2005

No abstracts.
Scale‐up und Miniplants
Authors: Zlokarnik M.
Published: June 2005

No abstracts.
Löslichkeit von Kohlendioxid in wässrigen, salzhaltigen Lösungen von Methanol bzw. Aceton
Authors: Jödecke M. , Xia J. , Pérez‐Salado Kamps Á. , Maurer G.
Published: June 2005

No abstracts.
Verbesserter Betrieb von Simulated Moving Bed‐Prozessen durch zyklische Modulation der Feedkonzentration
Authors: Schramm H. , Kaspereit M. , Kienle A. , Seidel‐Morgenstern A.
Published: June 2005

No abstracts.
Micellare Chromatographie
Authors: García Diez L. , Bart H.‐J. , Szymanowski J.
Published: June 2005

No abstracts.
Hochsensitive Partikelbestimmung mittels der laserinduzierten Break‐down‐Detektion
Authors: Bundschuh T. , Wagner T. , Köster R.
Published: June 2005

No abstracts.
Wechselfeldinduzierte Zell‐ und Teilchenbewegungen in Mikrokammern: Prinzipien, Anwendungen und Theorie
Authors: Gimsa J.
Published: June 2005

No abstracts.
Ursachen und Auswirkungen hydraulisch angeregter Schwingungen in Pumpen
Authors: Bross S. , Müller B.
Published: June 2005

No abstracts.
Neue Entwicklungen bei Anlagen und Verfahren für die Produktion von Pharmawirkstoffen
Authors: Behr A. , Brehme V.A. , Ewers C.L.J. , Grön H. , Kimmel T. , Küppers S. , Symietz I.
Published: June 2005

Die Pharmaindustrie befindet sich auf dem Weg in die Kostenfalle. Mehr und mehr setzt sich die Erkenntnis durch, dass klassische Stärken der Optimierung von Produktionstechnologien dort ansetzen können, wo Fusionen, Investitionen in High‐Through‐Put‐Screening und Biotechnologie bisher nicht die nötigen Erfolge gezeigt haben. Im vorliegenden Beitrag wird gezeigt, wie aus einer Kombination von innovativen Bausteinen eine leistungsfähige und deutlich kostengünstigere Produktion von Pharmawirkstoffen resultiert. Diese kann den Ausweg aus der Kostenfalle weisen. Ein erster Baustein, der betrachtet werden soll, ist der Anlagenbau, daneben ist eine deutlich stärkere Prozessorientierung als zweiter Baustein zu sehen. Die Technologien, die den dritten Baustein der neuen Produktionswege für Pharmawirkstoffe darstellen, sind die Miniplant‐Technologie und die Prozessanalytik. Zu letzterem technologischen Baustein werden anhand von Beispielen die Trends der Zukunft aufgezeigt.
Einsatzmöglichkeiten miniaturisierter Wärmeleistungssensoren in der Biotechnologie
Authors: Hüttl R. , Lerchner J. , Wolf A. , Wolf G.
Published: June 2005

No abstracts.
ELI_CAP‐Affinitätsmembran und Immobilisierungsmatrix für Life Sciences‐Anwendungen
Authors: Borcherding H. , Jorcke D. , Wilpert A. , Ulbricht M.
Published: June 2005

No abstracts.
Ein anaerob betriebener Membranbioreaktor zur vollständigen Kohlenstoffelimination aus schwach belasteten Abwässern
Authors: Fitzke B. , Geißen S.‐U. , Vogelpohl A.
Published: June 2005

No abstracts.
Biologisch‐chemische Verfahrenskombination zur Reinigung von Mischabwässern der Textilveredlung
Authors: Rapp T. , Wiesmann U.
Published: June 2005

No abstracts.
Kombinierte Abwasser‐ und Abluftreinigungsanlage für die Holzwerkstoffindustrie
Authors: Portenkirchner K. , Draxler J. , Somitsch W. , Stassen O.
Published: June 2005

No abstracts.
Bacterial infections in low‐risk, febrile neutropenic patients
Authors: Kamana Mallika , Escalante Carmelita , Mullen Craig A. , Frisbee‐Hume Susan , Rolston Kenneth V. I.
Published: June 2005

BACKGROUND

Accurate identification of low‐risk, febrile neutropenic patients has become possible only recently. Many such patients are treated with oral antibiotics without hospitalization. To the authors' knowledge, data concerning the spectrum of bacterial infections in these patients are scarce, and collecting such data may have an impact on the choice of empiric oral regimen(s).

METHODS

Using the same risk‐prediction and eligibility criteria, four studies of empiric therapy in low‐risk, febrile neutropenic patients were conducted at the authors' institution. Based on that experience, patients also were entered on clinical pathways for outpatient therapy. For the current study, microbiologic data were pooled from those trials and clinical pathways (757 episodes) to describe the nature and spectrum of infections seen in this setting.

RESULTS

Unexplained fever occurred most often (58% of episodes), and both clinically documented and microbiologically documented infections were seen with equal frequency (21% of episodes, respectively). The most common clinical sites of infection were the upper respiratory tract, skin, and skin structure. Among microbiologically documented infections, monomicrobial, gram‐positive infections accounted for 49% (with coagulase‐negative staphylococci the most frequent); monomicrobial, gram‐negative infections accounted for 36% (with Escherichia coli the most frequent); and 15% of infections were polymicrobial.

CONCLUSIONS

In this description of the spectrum of infections in the largest cohort of low‐risk febrile neutropenic patients to date, episodes of unexplained fever were predominant, but gram‐positive, gram‐negative, and polymicrobial infections also were documented. Although these patients were at low risk for complications, they required broad‐spectrum antibiotic therapy when they developed neutropenic fever. Cancer 2005. © 2005 American Cancer Society.
Radiotherapy alone or combined with carbogen breathing for squamous cell carcinoma of the head and neck
Authors: Mendenhall William M. , Morris Christopher G. , Amdur Robert J. , Mendenhall Nancy P. , Siemann Dietmar W.
Published: June 2005

BACKGROUND

The current study was performed to investigate the efficacy of carbogen (95% oxygen [O2] and 5% carbon dioxide [CO2]) breathing during definitive radiotherapy (RT) to enhance local control.

METHODS

Between November 1996 and November 2002, 101 patients with previously untreated T2 to T4 squamous cell carcinomas of the oropharynx, larynx, and hypopharynx were entered onto a prospective trial and randomized to receive definitive hyperfractionated RT alone or combined with carbogen breathing. Patients were stratified according to T classification and primary tumor site. Follow‐up ranged from 1–91 months (median, 38 months). All living patients had follow‐up for more than 2 years. Outcomes analyses were performed according to intent to treat.

RESULTS

Definitive RT alone was completed as planned in 50 of 51 patients (98%); 49 of the 50 patients (98%) who were randomized to receive carbogen breathing were able to complete the RT as planned. Three patients randomized to receive carbogen breathing declined carbogen. The 5‐year outcomes after RT alone or combined with carbogen were as follows: local control, 83% versus 88% (P = 0.5155); locoregional control, 81% versus 83% (P = 0.7174); distant metastasis‐free survival, 82% versus 86% (P = 0.5184); cause‐specific survival, 73% versus 77% (P = 0.5866); and absolute survival, 53% versus 58% (P = 0.4856).

CONCLUSIONS

The addition of carbogen breathing to definitive RT did not appear to improve the likelihood of local control significantly. However, because of the limited size of the current study, the authors cannot definitively conclude that carbogen breathing is ineffective. Cancer 2005. © 2005 American Cancer Society.
Long‐term clinical outcome of Helicobacter pylori eradication for gastric mucosa‐associated lymphoid tissue lymphoma with a reference to second‐line treatment
Authors: Nakamura Shotaro , Matsumoto Takayuki , Suekane Hiroshi , Nakamura Shigeo , Matsumoto Hiroshi , Esaki Motohiro , Yao Takashi , Iida Mitsuo
Published: June 2005

BACKGROUND

The goals of the current study were to elucidate the long‐term outcome of Helicobacter pylori eradication therapy for gastric mucosa‐associated lymphoid tissue (MALT) lymphoma and to clarify the therapeutic efficacy of stomach‐conserving treatments for patients not responding to eradication therapy.

METHODS

Ninety‐six patients with gastric MALT lymphoma, including 17 patients with areas of diffuse large B‐cell lymphoma, were treated by H. pylori eradication. Patients not responding to eradication therapy underwent either a gastrectomy, multiagent chemotherapy, oral monochemotherapy (OMC), or radiotherapy (RT). Predictive factors for the response to eradication therapy, overall survival (OS), and event‐free survival (EFS) were determined by the Kaplan–Meier analysis with the log‐rank test. The efficacy of second‐line treatment was compared between OMC and RT.

RESULTS

After eradication therapy, 62 (65%) patients achieved complete disease remission (CR). Transient histologic disease recurrence was confirmed in 4 (6.5%) of 62 patients with CR during the follow‐up (median, 37.5 months). The OS and EFS probabilities after 5 years were 0.96 and 0.80, respectively. Second‐line treatment was performed in 31 patients; gastrectomy in 4 patients, multiagent chemotherapy in 5 patients, OMC in 12 patients, and RT in 10 patients. There were no differences in the CR rate, OS, EFS, or toxicity between the OMC and RT groups.

CONCLUSIONS

H. pylori eradication therapy was an effective first‐line treatment for patients with gastric MALT lymphoma, which led to a favorable long‐term outcome. OMC and RT had an equivalent efficacy as a second‐line treatment in nonresponding patients to eradication therapy. Cancer 2005. © 2005 American Cancer Society.
Therapy strategies for locally advanced adenoid cystic carcinomas using modern radiation therapy techniques
Authors: Schulz‐Ertner Daniela , Nikoghosyan Anna , Didinger Bernd , Münter Marc , Jäkel Oliver , Karger Christian P. , Debus Juergen
Published: June 2005

BACKGROUND

The authors evaluated whether modern photon techniques, such as stereotactic fractionated radiation therapy (FSRT) or intensity‐modulated RT, outweighed the biologic advantages of high‐linear‐energy transfer RT in the treatment of patients with locally advanced adenoid cystic carcinomas (ACC) that infiltrated the skull base or the orbit.

METHODS

Between June 1995 and December 2003, 63 patients with ACC were treated with modern RT techniques at the University of Heidelberg. The treatment results achieved with modern photon techniques alone were compared with the results achieved with combined photon RT and a carbon ion boost. Twenty‐nine patients (Group A) were treated with a combination of photon RT and a carbon ion boost. Thirty‐four patients (Group B) received photon RT alone.

RESULTS

The median follow‐up was 16 months for Group A and 24 months for Group B. Locoregional control rates at 2 years and 4 years were 77.5% and 77.5% for Group A and 72.2% and 24.6% for Group B, respectively (P = 0.08; log‐rank test). Disease‐free and overall survival rates at 2 years/4 years were 71.5%/53% and 86.6%/75.8% for Group A and 69.2%/23% and 77.9%/77.9% for Group B, respectively. Rates for severe late toxicity were < 5% for both groups.

CONCLUSIONS

Modern RT techniques allowed the safe delivery of high target doses to patients with locally advanced ACC. Late toxicity rates were kept lower compared with the historic neutron therapy data. A combination of modern photon RT and carbon ion RT seemed to be advantageous, with a trend toward higher locoregional control rates compared with modern photon RT alone. Cancer 2005. © 2005 American Cancer Society.
Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma
Authors: Howell Anthony , Pippen John , Elledge Richard M. , Mauriac Louis , Vergote Ignace , Jones Stephen E. , Come Steven E. , Osborne C. Kent , Robertson John F.R.
Published: June 2005

BACKGROUND

Fulvestrant is an estrogen receptor antagonist with no agonist effects. In the second‐line treatment of advanced breast carcinoma, fulvestrant was shown previously to be as effective as the third‐generation aromatase inhibitor, anastrozole, in terms of time to disease progression and objective response rates. The authors reported the overall survival results from these studies.

METHODS

A prospectively planned, combined, overall survival analysis was performed, including data from two Phase III trials that compared the efficacy and tolerability of fulvestrant (250 mg monthly; n = 428) with anastrozole (1 mg daily; n = 423) in the treatment of postmenopausal women with advanced breast carcinoma who had disease progression after receipt of previous endocrine treatment.

RESULTS

At an extended median follow‐up of 27.0 months (range, 0–66.9 months), 319 (74.5%) patients in the fulvestrant group and 322 (76.1%) patients in the anastrozole group had died. Prolonged survival was observed with both drugs, with 10–20% of patients still alive > 5 years after randomization. The median overall survival was similar between treatments, being 27.4 months and 27.7 months in fulvestrant and anastrozole‐treated patients, respectively (hazards ratio, 0.98; 95% confidence interval, 0.84–1.15; P = 0.809). Fulvestrant continued to be well tolerated, and was associated with a significantly lower incidence of joint disorders compared with anastrozole (P = 0.0234).

CONCLUSIONS

The current analysis showed that fulvestrant was similar to anastrozole with respect to overall survival in the second‐line treatment of postmenopausal women with advanced breast carcinoma. Cancer 2005. © 2005 American Cancer Society.
Barriers to minority participation in breast carcinoma prevention trials
Authors: Grann Victor R. , Jacobson Judith S. , Troxel Andrea B. , Hershman Dawn , Karp Julie , Myers Christa , Neugut Alfred I.
Published: June 2005

BACKGROUND

Breast carcinoma prevention trials must recruit large cohorts of women who have an above‐average risk of developing breast carcinoma. Recruitment for the Study of Tamoxifen and Raloxifene (STAR) trial required volunteers to complete a risk assessment questionnaire form (RAF). Women whose estimated risk of developing breast carcinoma in the next 5 years was ≥ 1.67% based on the Gail model were invited to participate in STAR. Less than 4% of participants in the previously conducted P1 (tamoxifen vs. placebo) trial were minority women. We, therefore, studied barriers to minority participation in STAR among black, white, and Hispanic women who completed an RAF.

METHODS

The authors analyzed the association of Gail model risk factors, education, and insurance with race/ethnicity using chi‐square tests and two‐sided P values. They developed logistic regression models of trial eligibility, controlling for the Gail model risk factors, education, and insurance status.

RESULTS

Among 823 women who completed an RAF, white women were 10 times as likely as Hispanic women and 45 times as likely as black women to be eligible for STAR. Age at first birth (P = 0.04), having an affected first‐degree relative (P < 0.0001), having had a biopsy (P < 0.0001), education (P < 0.0001), and insurance status (P < 0.0001) varied by race/ethnicity. All variables except insurance status were associated with eligibility when race was excluded from the model. In a model that included race/ethnicity, the same factors remained statistically significant.

CONCLUSIONS

These findings suggested that both the race/ethnicity adjustment and socioeconomic factors were barriers to eligibility for and contribute to low minority participation in breast cancer prevention trials. Cancer 2005. © 2005 American Cancer Society.
Automated image analysis methods for 3‐D quantification of the neurovascular unit from multichannel confocal microscope images
Authors: Lin Gang , Bjornsson Chris S. , Smith Karen L. , Abdul‐Karim Muhammad‐Amri , Turner James N. , Shain William , Roysam Badrinath
Published: June 2005

Background

There is a need for integrative and quantitative methods to investigate the structural and functional relations among elements of complex systems, such as the neurovascular unit (NVU), that involve multiple cell types, microvasculatures, and various genomic/proteomic/ionic functional entities.

Methods

Vascular casting and selective labeling enabled simultaneous three‐dimensional imaging of the microvasculature, cell nuclei, and cytoplasmic stains. Multidimensional segmentation was achieved by (i) bleed‐through removal and attenuation correction; (ii) independent segmentation and morphometry for each corrected channel; and (iii) spatially associative feature computation across channels. The combined measurements enabled cell classification based on nuclear morphometry, cytoplasmic signals, and distance from vascular elements. Specific spatial relations among the NVU elements could be quantified.

Results

A software system combining nuclear and vessel segmentation codes and associative features was constructed and validated. Biological variability contributed to misidentified nuclei (9.3%), undersegmentation of nuclei (3.7%), hypersegmentation of nuclei (14%), and missed nuclei (4.7%). Microvessel segmentation errors occurred rarely, mainly due to nonuniform lumen staining.

Conclusions

Associative features across fluorescence channels, in combination with standard features, enable integrative structural and functional analysis of the NVU. By labeling additional structural and functional entities, this method can be scaled up to larger‐scale systems biology studies that integrate spatial and molecular information. © 2005 Wiley‐Liss, Inc.
Spectral efficiency of a cellular MC/DS‐CDMA system in Rayleigh fading
Authors: Varzakas P. , Tombras G. S.
Published: June 2005

The spectral efficiency of a multicarrier direct‐sequence code‐division multiple‐access (MC/DS‐CDMA) cellular system, operating in a mobile radio environment with Rayleigh fading, is investigated and evaluated in terms of channel capacity (in the Shannon sense) per user, estimated in an average sense. The analysis is based on the combination of path‐diversity reception, achieved by a conventional coherent maximal‐ratio combining (MRC) RAKE receiver and the physical frequency diversity potential provided by orthogonal frequency division multiplexing (OFDM). As shown, a closed‐form expression for the achieved spectral efficiency of the considered system's operation is derived following a recently presented general method. Copyright © 2005 John Wiley & Sons, Ltd.
GCN5 and p300 share essential functions during early embryogenesis
Authors: Phan Huy M. , Xu Allison W. , Coco Cherie , Srajer Geraldine , Wyszomierski Shannon , Evrard Yvonne A. , Eckner Richard , Dent Sharon Y.R.
Published: June 2005

Previous studies revealed that deletion of genes encoding the histone acetyltransferases GCN5, p300, or CBP results in embryonic lethality in mice. PCAF and GCN5 physically interact with p300 and CBP in vitro. To determine whether these two groups of histone acetyltransferases interact functionally in vivo, we created mice lacking one or more alleles of p300, GCN5, or PCAF. As expected, we found that mice heterozygous for any single null allele are viable. The majority of GCN5+/−p300+/− mice also survive to adulthood with no apparent abnormalities. However, ∼25% of these mice die before birth. These embryos are developmentally stunted and exhibit increased apoptosis compared with wild‐type or single GCN5+/− or p300+/− littermates at embryonic day 8.5. In contrast, no abnormalities were observed in PCAF−/− p300+/− mice. Of interest, we find that p300 protein levels vary in different mouse genetic backgrounds, which likely contributes to the incomplete penetrance of the abnormal phenotype of GCN5+/− p300+/− mice. Our data indicate that p300 cooperates specifically with GCN5 to provide essential functions during early embryogenesis. Developmental Dynamics 233:1337–1347, 2005. © 2005 Wiley‐Liss, Inc.
Cellular inheritance of a Cre‐activated reporter gene to determine paneth cell longevity in the murine small intestine
Authors: Ireland Heather , Houghton Carol , Howard Louise , Winton Douglas J.
Published: June 2005

Here, we exploit an absolute differential between stem and progeny cells in their ability to express Cre from a somatically inducible transgene to determine the longevity of intestinal Paneth cells. In the Ahcre transgenic line induction of Cre recombinase allows constitutive activation of a Cre‐activated reporter in intestinal precursors but not in Paneth cells. The time taken for Paneth cells to inherit the reporter (EYFP) was measured in adult Ahcre/R26R‐EYFP animals. Using confocal microscopy of TOPRO‐3–stained sections, both precursors and Paneth cells were identified and subsequently scored for EYFP expression. It takes up to 57 days for Paneth cells to inherit the reporter, making them three times longer‐lived than previously indicated using nucleotide incorporation and suggesting that such determinations of cell turnover may be significant underestimates. Developmental Dynamics 233:1332–1336, 2005. © 2005 Wiley‐Liss, Inc.
Runx3 is involved in hair shape determination
Authors: Raveh Eli , Cohen Shulamit , Levanon Ditsa , Groner Yoram , Gat Uri
Published: June 2005

Transcriptional regulators of the Runx family play critical roles in normal organ development and, when mutated, lead to genetic diseases and cancer. Runx3 functions during cell lineage decisions in thymopoiesis and neurogenesis and mediates transforming growth factor‐β signaling in dendritic cells. Here, we study the function of Runx3 in the skin and its appendages, primarily the hair follicle, during mouse development. Runx3 is expressed predominantly in the dermal compartment of the hair follicles as they form and during the hair cycle, as well as in the nail and sweat gland skin appendages. Distinct expression is also detected periodically in isolated cells of the epidermis and in melanocytes, populating the hair bulb. Runx3‐deficient mice display a perturbation of the normal hair coat, which we show to be due to hair type and hair shape changes. Thus, one of the functions of Runx3 in skin may be to regulate the formation of the epithelial derived structural hair by affecting dermal to epidermal interactions. Developmental Dynamics 233:1478–1487, 2005. © 2005 Wiley‐Liss, Inc.
Slowly Exchanging cis‐PtA2B2 Atropisomers with A2 = Chiral Diamine Ligands and B = 5,6‐Dimethylbenzimidazole
Authors: Trani Manuela , Cannito Francesco , Natile Giovanni , Marzilli Patricia A. , Marzilli Luigi G.
Published: June 2005

cis‐PtA2G2 complexes, in which A2 is a bidentate amine ligand and G is a unidentate guanine derivative bound to platinum through N7, are simple models of the G‐G cross‐link DNA lesion formed by the anticancer drug cisplatin. Rotation of the G bases about the Pt–N7 bonds is usually rapid except for bulky amine ligand(s). This paper concerns cis‐PtA2(Me2Bzm)2 adducts [A2 = 2,2'‐bipiperidine (Bip)and N,N,N',N'‐tetramethyl‐2,3‐diaminobutane (Me4DAB); Me2Bzm = 5,6‐dimethylbenzimidazole] for which the interconversion among possible rotamers (one HH and two HT) is slow on the NMR time scale. The amounts of the rarely observed HH conformer were 52 and 37 % at 5 °C for BipPt(Me2Bzm)2 and Me4DABPt(Me2Bzm)2, respectively, and increased to 60 and 44 % at 50 °C. This result represents the first reported clear evidence for the existence of the HH atropisomer in cis‐PtA2B2 adducts (B = G or Me2Bzm base) with fully substituted diamines, such as Me4DAB or Me4EN (Me4EN = N,N,N',N'‐tetramethyl‐1,2‐diaminoethane). The lack of an O‐substituent on the C4 atom of Me2Bzm (corresponding to C6 of G) undoubtedly allows for a relatively stable HH conformer. Thermodynamic parameters confirm the crucial role of the substituents in positions 4 and 6 of the base systems (for Me2Bzm and G derivatives, respectively) in determining the stability of different rotamers. The greater abundance of the HH rotamer for BipPt(Me2Bzm)2 than for Me4DABPt(Me2Bzm)2 indicates that an increase in the steric bulk of the carrier ligand favors the HT rotamers over the HH rotamer. For both BipPt(Me2Bzm)2 and Me4DABPt(Me2Bzm)2 adducts, the major HT rotamer has the six‐membered ring of each Me2Bzm ligand on the more crowded side of the cis amine with respect to the platinum coordination plane: the N–CH2– group in Bip and the N–Meeq (N–Meeq = quasi‐equatorial N–Me) in Me4DAB adducts. The latter result is in complete agreement with previous findings from our laboratories concerning BipPtG2 and Me4DABPtG2 compounds and gives further support to the view that the major HT rotamer is stabilized by the six‐membered ring of each base canted toward the cis base. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
[1]Borahafnocenophanes: Synthesis, Structure and Catalytic Activity
Authors: Braunschweig Holger , Kraft Mario , Radacki Krzysztof , Stellwag Sascha
Published: June 2005

Various [1]borahafnocenophanes of the general formula[R2NB(η5‐C5H4)2HfCl2] [R = CH3, 13; R = C2H5, 14; R2 =(CH2)5, 15] were synthesised in high yields by a convenient two‐step, one‐pot synthesis, and their constitution in solution elucidated from multinuclear NMR spectroscopic data. Suitable single crystals of complexes 13 and 15 were subjected to X‐ray diffraction studies, thus providing the first structural data of [1]borahafnocenophanes. The catalytic activity of the new complexes in the Ziegler–Natta polymerisation of ethylene was studied and compared to that of corresponding [1]borazirconocenophanes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Design, Preparation and Characterization of the Adducts of the Bis‐Amido Cobalticinium Complex [CoIII(η5‐C5H4CONHC5H4N)2][PF6] with Fumaric and Maleic Acids
Authors: Braga Dario , Giaffreda Stefano L. , Polito Marco , Grepioni Fabrizia
Published: June 2005

The supramolecular hydrogen‐bonded adducts obtained by treating the cationic bis‐amido complex [CoIII(η5‐C5H4CONHC5H4N)2]+ with fumaric and maleic acid are investigated and their modes of aggregation in the solid state are explored. It is shown that the bis‐amido organometallic complex can be mono‐ and di‐protonated in the reaction with the dicarboxylic acids, leading to the formation of complex, mixed‐anion supramolecular salts containing either the dication [CoIII(η5‐C5H4CONHC5H4N)(η5‐C5H4CONHC5H4NH)]2+, [1H]2+, or the trication [CoIII(η5‐C5H4CONHC5H4NH)2]3+, [1H2]3+. The derivatives of the reaction with fumaric acid, namely, [CoIII(η5‐C5H4CONHC5H4N)(η5‐C5H4CONHC5H4NH)]2+·[PF6]–·1/2[fumarate]2–, [1H]2+·PF6–·1/2[fumarate]2–, and [CoIII(η5‐C5H4CONHC5H4NH)2]3+·[PF6]–·[H(fumarate)2]3–·H3O+·H2O, [1H2]3+·[PF6]–·[H(fumarate)2]3–·H3O+·H2O, contain either the dianion [fumarate]2– or the hydrogen‐bridged supramolecular trianion [H(fumarate)2]3–, depending on the amide/acid stoichiometric ratio. In the case of maleic acid, on the other hand, the possibility of intramolecular hydrogen‐bond formation generates exclusively salts of the hydrogen maleate anions, namely, [CoIII(η5‐C5H4CONHC5H4N)(η5‐C5H4CONHC5H4NH)]2+·5/2[PF6]–·3/2[Hmaleate]–, 2[1H]2+·5/2[PF6]–·3/2[Hmaleate]–, 2[CoIII(η5‐C5H4CONHC5H4NH)2]3+·3[PF6]–·3[Hmaleate]–·2H2O, 2[1H2]3+·3[PF6]–·3[Hmaleate]–·2H2O and [CoIII(η5‐C5H4CONHC5H4NH)2]3+·2[PF6]–·[Hmaleate]–·H2O, [1H2]3+·2[PF6]–·[Hmaleate]–·H2O, in which the hydrogen maleate anions act as bridges between the protonated bis‐amido organometallic sandwiches. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
ChiralN‐Acylhydrazones: Versatile Imino Acceptors for Asymmetric Amine Synthesis
Authors: Friestad Gregory K.
Published: June 2005

Addition to C=N bonds with acyclic stereocontrol offers excellent potential for development of new carbon–carbon bond construction approaches to chiral amines. This review features the design and implementation of novel chiralN‐acylhydrazones as versatile imino acceptors for addition of radicals and nucleophiles. The initial design was inspired by the goal of asymmetric radical addition to chiral C=N radical acceptors. The chiralN‐acylhydrazones are prepared from commercially available materials by amination of 4‐alkyl‐2‐oxazolidinones with NH2+equivalents to affordN‐(amino)oxazolidinones, followed by condensation with aldehydes or ketones. These chiralN‐acylhydrazones undergo addition reactions with various partners, including radicals, allylsilanes, allylindiums, silyl enol ethers, and hydride donors. The adducts can be converted to chiral amines by N–N bond cleavage. Reliably high stereoselectivity was observed for addition reactions in the presence of Lewis acids. For the prototype case,N‐acylhydrazones derived from (S)‐4‐benzyl‐2‐oxazolidinone, two alternative stereocontrol models are consistent with the results. Lewis acids capable of chelate formation activate through two‐point binding of the imino nitrogen and the carbonyl oxygen, exposing thesi‐face for addition. On the other hand, boron trifluoride activates through a monodentate interaction, favoring a rotamer which exposes there‐face. Applications from the author’s research program are reviewed together with results from other groups. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Analysis of carboxylic acids in biological fluids by capillary electrophoresis
Authors: Baena Beatriz , Cifuentes Alejandro , Barbas Coral
Published: June 2005

This review article addresses the different capillary electrophoretic methods that are being used for the study of both short‐chain organic acids (including anionic catecholamine metabolites) and fatty acids in biological samples. This work intends to provide an updated overview (including works published until November 2004) on the recent methodological developments and applications of such procedures together with their main advantages and drawbacks. Moreover, the usefulness of CE analysis of organic acids to study and/or monitor different diseases such as diabetes, new‐borns diseases or metabolism disorders is examined. The use of microchip devices and CE‐MS couplings for organic acid analysis is also discussed.
High‐throughput gender determination using automated denaturant gel capillary electrophoresis
Authors: Hinselwood David C. , Warren David J. , Ekstrøm Per O.
Published: June 2005

Sex determination of anonymous samples is a requirement before analysis of DNA variation on X or Y chromosomes. Based on this, we designed a method for screening samples on different DNA capillary sequencing instruments with a sensitivity that is able to quantify sex chromosome abnormalities. The two different amelogenin alleles sited on the X and Y chromosomes were polymerase chain reaction amplified with the same set of primers and separated by denaturant capillary electrophoresis (DCE). Sex chromosome ratios could be reproducibly determined with a relative standard deviation of 8.7%, which is sufficient to distinguish a normal XY karyotype from an XYY karyotype associated with Klinefelter syndrome. Reconstruction experiments demonstrated sensitivity down to a simulated Y:X allelic ratio of 1:127 in all three instruments, enabling the prediction of sex chromosomal aneuploidies. When tested on anonymous pooled and single samples, DCE gave a good prediction of the male to female ratio in pools of 1000 blood donors. In conclusion, DCE is a simple and robust method for sex determination that can be readily performed on commercially available CE systems.
Review of denaturant capillary electrophoresis in DNA variation analysis
Authors: Bjørheim Jens , Ekstrøm Per Olaf
Published: June 2005

Analyses of germline and somatic single‐nucleotide DNA variations are important in both population genetics research and clinical practice. Reliable and inexpensive methods that are flexible and designed for automation are required for these analyses. Present day DNA sequencing technology is too expensive for testing all 22–25 000 human genes in populations genetics studies or in scanning large numbers of tumors for novel mutations. Denaturant capillary electrophoresis (DCE) has the potential to meet the need for large‐scale analysis of DNA variants. Several different analyses can be performed by DCE, including mutation analysis, single‐nucleotide polymorphism (SNP) discovery in individual and pooled samples, detection of allelic imbalance, and determination of microhaplotypes. Here we review the theoretical background of the method, its sensitivity, specificity, detection limit, throughput, and repeatability in the light of current literature in the field.
Locus‐specific brackets for reliable typing of Y‐chromosome short tandem repeat markers
Authors: Butler John M. , Appleby Jill E. , Duewer David L.
Published: June 2005

Short tandem repeat (STR) loci, widely used as genetic markers in disease diagnostic studies and human identity applications, are traditionally genotyped through comparison of allele sizes to a sequenced allelic ladder. Allelic ladders permit a floating bin allele calling method to be utilized, which enables reliable allele calling across laboratories, instrument platforms, and electrophoretic conditions. Precise sizing methods for STR allele calling involving fixed bins can also be used when a high degree of precision has been demonstrated within an instrument platform and a set of electrophoretic conditions. An alternative method for reliable genotyping of STR markers, locus‐specific brackets (LSBs), is introduced here. LSBs are artificial alleles created through molecular biology manipulations to be shorter or longer than alleles commonly seen in populations under investigation. The size and repeat number of measured alleles are interpolated between the two LSB products that are mixed with the polymerase chain reaction‐amplified STR alleles. The advantages and limitations of the LSB approach are described along with a concordance study between the LSB typing approach and other STR typing methods. Complete agreement was observed with 162 samples studied at 5 Y‐chromosome loci.
Direct targeting of human plasma for matrix‐assisted laser desorption/ionization and analysis of plasma proteins by time of flight‐mass spectrometry
Authors: Jin Ya , Manabe Takashi
Published: June 2005

A method to analyze human plasma proteins without fractionation, directly applying a plasma‐matrix mixture on the target plate of a matrix‐assisted laser desorption/ionization‐time of flight‐mass spectrometer (MALDI‐TOF‐MS), has been described. Peaks of ionized plasma proteins could not be detected applying a mixture of an undiluted plasma sample and a matrix solution, but they appeared when the plasma was diluted before mixing with the matrix. Tenfold diluted plasma provided well‐resolved protein peaks in the m/z range from 4000 to 30 000. The addition of a simple post‐crystallization washing procedure performed on the target plate further improved the quality of mass spectra. We numbered 58 peaks in the range of 4–160 kDa and 32 out of which were assigned to the plasma protein species which have been reported. Especially high sensitivity and resolution were obtained in the region < 30 kDa, where multiple isoforms of apolipoprotein A‐I, apolipoprotein A‐II, apolipoprotein C‐I, apolipoprotein C‐II, apolipoprotein C‐III, and transthyretin could be assigned. Various post‐translational modifications are involved in the isoforms, e.g., proteolytic cleavage, glycosylation and chemical modifications. This method will become complementary with the present electrophoretic techniques, especially for the analysis of low‐molecular‐mass proteins.
Determination of mercaptopurine and its four metabolites by large‐volume sample stacking with polarity switching in capillary electrophoresis
Authors: Wang Chun‐Chi , Chiou Shyh‐Shin , Wu Shou‐Mei
Published: June 2005

This study describes approaches for stacking a large volume of sample solutions containing a mixture of mercaptopurine monohydrate, 6‐methylmercaptopurine, thioguanine, thioguanosine, and thioxanthine in capillary electrophoresis (CE). After filling the run buffer (60 mM borate buffer, pH 8.5), a large sample volume was loaded by hydrodynamic injection (2.5 psi, 99.9 s), followed by the removal of the large plug of sample matrix from the capillary using polarity switching (−15 kV). Monitoring the current and reversing the polarity when 95% of current recovered, the separation of anionic analytes was performed in a run buffer < 20 kV. Around 44‐ to 90‐fold improvement of sensitivity for five analytes was achieved by large‐volume stacking with polarity switching when compared with CE without stacking. This method was feasible for determination of the analytes spiked in plasma. Removing most of electrolytes from plasma is a key step for performing large‐volume sample stacking. Solid‐phase extraction was used for pretreatment of biological samples. To our knowledge, this study is one of few applications showing the possibilities of this stacking procedure to analyze biological samples by large‐volume sample stacking with polarity switching (LVSSPS) in CE.
Paddy Rice and the Water Supply
Authors: Sattelmacher Burkhard , Dittert Klaus , Lin Shan
Published: June 2005

Over half of Asia′s fresh water is used for growing rice. A new procedure in China has been developed to test a new water‐saving cultivation system
Not of this World
Authors: Vossen Joachim
Published: June 2005

Time seems to have stood still for the Amish people of Lancaster County, Pennsylvania. Even in the modern world, these descendants of German and Swiss Anabaptists still live according to their traditional roots
Climatic Trends and the Pressure Seesaw
Authors: Brümmer Burghard
Published: June 2005

In our latitudes, weather can be forecast for a few days. However, what determines the long‐term variations and trends in the North Atlantic climate system still remains largely unknown. Meteorologists are investigating the fundamentals
When the Biological Pump is Perturbed
Authors: Eickhoff Susanne , Ittekkot Venugopalan , Jennerjahn Tim
Published: June 2005

Throughout the world, there are about 45,000 dams interrupting the natural flow of water to the oceans. This significantly affects the silicon cycle, endangering the ecological balance