bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing a guideline for the treatment of type 2 diabetics: results of a Cluster- Randomized Controlled Trial (C-RCT)
Authors: Perria Carla , Mandolini Donatella , Guerrera Carmelina , Jefferson Tom , Billi Paolo , Calzini Virgilio , Fiorillo Alfonso , Grasso Giuseppe , Leotta Sergio , Marrocco Walter , Suraci Concetta , Pasquarella Amina
Published: June 2007

Background

In Italy many diabetics still lack adequate care in general practice. We assessed the effectiveness of different strategies for the implementation of an evidence-based guideline for the management of non-complicated type 2 diabetes among General Practitioners (GPs) of Lazio region.

Methods

Three-arm cluster-randomised controlled trial with GPs as units of randomisation (clusters). 252 GPs were randomised either to an active strategy (training module with administration of the guideline), or to a passive dissemination (administration of the guideline only), or to usual care (control). Data on prescriptions of tests and drugs were collected by existing information systems, whereas patients' data came from GPs' databases. Process outcomes were measured at the cluster level one year after the intervention. Primary outcomes concerned the measurement of glycosilated haemoglobin and the commissioning of micro- and macrovascular complications assessment tests. In order to assess the physicians' drug prescribing behaviour secondary outcomes were also calculated.

Results

GPs identified 6395 uncomplicated type 2 patients with a high prevalence of cardiovascular risk factors. Data on GPs baseline performance show low proportions of glycosilated haemoglobin assessments. Results of the C-RCT analysis indicate that the active implementation strategy was ineffective relating to all primary outcomes (respectively, OR 1.06 [95% IC: 0.76–1.46]; OR 1.07 [95% IC: 0.80–1.43]; OR 1.4 [95% IC:0.91–2.16]. Similarly, passive dissemination of the guideline showed no effect.

Conclusion

In our region compliance of GPs with guidelines was not enhanced by a structured learning programme. Implementation through organizational measures appears to be essential to induce behavioural changes.

Trial registration

ISRCTN80116232
Selective cytotoxicity of Pancratistatin-related natural Amaryllidaceae alkaloids: evaluation of the activity of two new compounds
Authors: Griffin Carly , Sharda Natasha , Sood Divya , Nair Jerald , McNulty James , Pandey Siyaram
Published: June 2007

Background

Pancratistatin (PST), a compound extracted from an Amaryllidaceae (AMD) family plant, has been shown to specifically induce apoptosis in cancer cells with no/minimal toxic effect on normal cells. A systematic synthetic approach has indicated that the minimum cytotoxic pharmacophore comprises the trans-fused b/c-ring system containing the 2, 3, 4-triol unit in the C-ring. To further explore the structure-activity relationship of this group of compounds we have investigated the anti-cancer efficacy and specificity of two PST-related natural compounds, AMD4 and AMD5. Both of these compounds lack the polyhydroxylated lycorane element of PST instead having a methoxy-substuituted crinane skeleton.

Results

Our results indicate that AMD5 has efficacy and selectivity similar to PST, albeit at a 10-fold increased concentration. Interestingly AMD4 lacks apoptotic activity.

Conclusion

Our results indicate that the phenanthridone skeleton in natural Amaryllidaceae alkaloids may be a significant common element for selectivity against cancer cells; furthermore, the configuration of the methoxy-side groups is responsible for higher binding affinity to the target protein/s thus making for a more efficient anti-cancer agent.
hZip2 and hZip3 zinc transporters are down regulated in human prostate adenocarcinomatous glands
Authors: Desouki Mohamed M , Geradts Joseph , Milon Beatrice , Franklin Renty B , Costello Leslie C
Published: June 2007

Background

The normal human prostate glandular epithelium has the unique function of accumulating high levels of zinc. In prostate cancer this capability is lost as an early event in the development of the malignant cells. The mechanism and factors responsible for the ability of the normal epithelial cells to accumulate zinc and the loss of this capability in the malignant cells need to be identified. We previously reported that Zip1 is an important zinc uptake transporter in prostate cells and is down regulated in the malignant cells in situ along with the depletion of zinc levels. In this report we investigated the expression of two other Zip family zinc transporters, Zip2 and Zip3 in malignant versus nonmalignant (normal and BPH) glands. Zip2 and Zip3 relative protein levels were determined by immunohistochemistry analysis of human prostate tissue sections.

Results

Normal and BPH glandular epithelium consistently exhibited the strong presence of both Zip 2 and Zip3; whereas both transporters consistently were essentially non-detectable in the malignant glands. This represents the first report of the expression of Zip3 in human prostate tissue; and more importantly, reveals that ZiP2 and Zip3 are down regulated in malignant cells in situ as we also had demonstrated for Zip1. Zip2 and Zip3 transporter proteins were localized predominantly at the apical cell membrane, which is in contrast to the Zip1 localization at the basolateral membrane. Zip2 and Zip3 seemingly are associated with the re-uptake of zinc from prostatic fluid.

Conclusion

These results coupled with previous reports implicate Zip2 and Zip3 along with Zip1 as important zinc uptake transporters involved in the unique ability of prostate cells to accumulate high cellular zinc levels. Zip1 is important for the extraction of zinc from circulation as the primary source of cellular zinc. Zip 2 and Zip3 appear to be important for retention of the zinc in the cellular compartment. The down regulation of all three transporters in the malignant cells is consistent with the loss of zinc accumulation in these cells. Since zinc imposes tumor suppressor effects, the silencing of the gene expression for these transporters is a required event for the manifestation of the malignant activities of the neoplastic cells. This now provides new insights into the genetic/molecular events associated with the development of prostate cancer; and supports our concept of Zip1, and now Zip2 and Zip3, as tumor suppressor genes and zinc as a tumor suppressor agent.
The impact of splenectomy on outcomes after distal and total pancreatectomy
Authors: Koukoutsis Ilias , Tamijmarane Appou , Bellagamba Riccardo , Bramhall Simon , Buckels John , Mirza Darius
Published: June 2007

Background

Several authors advocate spleen preserving distal pancreatectomy, because of the increased complication rate after splenectomy.

Methods

Postoperative complications and survival after distal and total pancreatectomy, were recorded and retrospectively analyzed according to spleen preservation. Patients, who underwent distal and total pancreatectomy without histologically proven adenocarcinoma, or extrapancreatic disease, were included in the cohort which was divided into splenectomy and no splenectomy groups. Statistical analysis was performed using Fisher's test.

Results

The study group consisted of 62 patients who underwent distal and total pancreatectomy between 26/11/1987 to 6/1/2006. Splenectomy was performed in 35 out of 62 patients (56.5%), distal pancreatectomy was performed in 49 out of 62 patients (79%). Morbidity rate was 28.6% in splenectomy group and 14.8% in the no splenectomy group (p = 0.235), while 30 days mortality rate was 2.9%; one patient died in the splenectomy group (p = 1).

Conclusion

Spleen-preservation did not influence the outcomes after distal and total pancreatectomy in our series.
Lentiviral vector design using alternative RNA export elements
Authors: Oh Taekeun , Bajwa Ali , Jia Guangfu , Park Frank
Published: June 2007

Background

Lentiviral vectors have been designed with complex RNA export sequences in both the integrating and packaging plasmids in order to co-ordinate efficient vector production. Recent studies have attempted to replace the existing complex rev/RRE system with a more simplistic RNA export system from simple retroviruses to make these vectors in a rev-independent manner.

Results

Towards this end, lentiviral transfer plasmids were modified with various cis-acting DNA elements that co-ordinate RNA export during viral production to determine their ability to affect the efficiency of vector titer and transduction in different immortalized cell lines in vitro. It was found that multiple copies of the constitutive transport element (CTE) originating from different simian retroviruses, including simian retrovirus type 1 (SRV-1) and type-2 (SRV-2) and Mason-Pfizer (MPV) could be used to eliminate the requirement for the rev responsive element (RRE) in the transfer and packaging plasmids with titers >106 T.U./mL (n = 4–8 preparations). The addition of multiple copies of the murine intracisternal type A particle, the woodchuck post-regulatory element (WPRE), or single and dual copies of the simian CTE had minimal effect on viral titer. Immortalized cell lines from different species were found to be readily transduced by VSV-G pseudotyped lentiviral vectors containing the multiple copies of the CTE similar to the findings in HeLa cells, although the simian-derived CTE were found to have a lower infectivity into murine cell lines compared to the other species.

Conclusion

These studies demonstrated that the rev-responsive element (RRE) could be replaced with other constitutive transport elements to produce equivalent titers using lentivectors containing the RRE sequence in vitro, but that concatemerization of the CTE or the close proximity of RNA export sequences was needed to enhance vector production.
Expression of RNA virus proteins by RNA polymerase II dependent expression plasmids is hindered at multiple steps
Authors: Ternette Nicola , Stefanou Daniela , Kuate Seraphin , Überla Klaus , Grunwald Thomas
Published: June 2007

Background

Proteins of human and animal viruses are frequently expressed from RNA polymerase II dependent expression cassettes to study protein function and to develop gene-based vaccines. Initial attempts to express the G protein of vesicular stomatitis virus (VSV) and the F protein of respiratory syncytial virus (RSV) by eukaryotic promoters revealed restrictions at several steps of gene expression.

Results

Insertion of an intron flanked by exonic sequences 5'-terminal to the open reading frames (ORF) of VSV-G and RSV-F led to detectable cytoplasmic mRNA levels of both genes. While the exonic sequences were sufficient to stabilise the VSV-G mRNA, cytoplasmic mRNA levels of RSV-F were dependent on the presence of a functional intron. Cytoplasmic VSV-G mRNA levels led to readily detectable levels of VSV-G protein, whereas RSV-F protein expression remained undetectable. However, RSV-F expression was observed after mutating two of four consensus sites for polyadenylation present in the RSV-F ORF. Expression levels could be further enhanced by codon optimisation.

Conclusion

Insufficient cytoplasmic mRNA levels and premature polyadenylation prevent expression of RSV-F by RNA polymerase II dependent expression plasmids. Since RSV replicates in the cytoplasm, the presence of premature polyadenylation sites and elements leading to nuclear instability should not interfere with RSV-F expression during virus replication. The molecular mechanisms responsible for the destabilisation of the RSV-F and VSV-G mRNAs and the different requirements for their rescue by insertion of an intron remain to be defined.
Pain-Related Anxiety-Like Behavior Requires CRF1 Receptors in the Amygdala
Authors: Ji Guangchen , Fu Yu , Ruppert Katherine A , Neugebauer Volker
Published: June 2007

Corticotropin-releasing factor receptor CRF1 has been implicated in the neurobiological mechanisms of anxiety and depression. The amygdala plays an important role in affective states and disorders such as anxiety and depression. The amygdala is also emerging as a neural substrate of pain affect. However, the involvement of the amygdala in the interaction of pain and anxiety remains to be determined. This study tested the hypothesis that CRF1 receptors in the amygdala are critically involved in pain-related anxiety. Anxiety-like behavior was determined in adult male rats using the elevated plus maze (EPM) test. The open-arm preference (ratio of open arm entries to the total number of entries) was measured. Nocifensive behavior was assessed by measuring hindlimb withdrawal thresholds for noxious mechanical stimulation of the knee. Measurements were made in normal rats and in rats with arthritis induced in one knee by intraarticular injections of kaolin/carrageenan. A selective CRF1 receptor antagonist (NBI27914) or vehicle was administered systemically (i.p.) or into the central nucleus of the amygdala (CeA, by microdialysis). The arthritis group showed a decreased preference for the open arms in the EPM and decreased hindlimb withdrawal thresholds. Systemic or intraamygdalar (into the CeA) administration of NBI27914, but not vehicle, inhibited anxiety-like behavior and nocifensive pain responses, nearly reversing the arthritis pain-related changes. This study shows for the first time that CRF1 receptors in the amygdala contribute critically to pain-related anxiety-like behavior and nocifensive responses in a model of arthritic pain. The results are a direct demonstration that the clinically well-documented relationship between pain and anxiety involves the amygdala.
Morbidity associated with systemic corticosteroid preparation for coronary artery bypass grafting in patients with chronic obstructive pulmonary disease: a case control study
Authors: Starobin Daniele , Kramer Mordechai Rehuven , Garty Moshe , Shitirt David
Published: June 2007

Background

Coronary artery bypass grafting (CABG) is associated with high morbidity in patients with chronic obstructive pulmonary disease (COPD).

We examine the effect of preoperative systemic corticosteroids on morbidity in this setting.

Methods

Ninety candidates for elective CABG participated in a prospective, open randomized trial, including 30 patients with COPD who received a single injection of a long-acting corticosteroid, 30 with COPD who received placebo, and 30 without COPD who served as controls. Primary end-points were postoperative pulmonary and nonpulmonary complications. Secondary end-points were length of hospital stay (LOS), ICU stay of less than 24 hours and more than 48 hours, duration of mechanical ventilation, and time to walking and sitting.

Results

The rate of pulmonary complications was similar in the two COPD groups and in the COPD patients and controls. The placebo group had more major nonpulmonary complications than the treatment group, but the difference was not statistically significant (26% vs. 17%, P = NS). The non-COPD control group had significantly fewer nonpulmonary complications than the COPD patients (treatment+placebo) (33% vs 70%, P = 0.014) and a similar rate of pulmonary complications. There was a statistically significant difference between the treated and placebo COPD groups in ICU stay less than 24 hours (P ≤ 0.001) and more than 48 hours (P = 0.03) and hospital stay (P = 0.013). On stepwise analysis, only age and number of coronary grafts were predictors of pulmonary complications.

Conclusion

The use of preoperative systemic corticosteroids in patients with COPD undergoing CABG may shorten ICU and hospital stay.
Non-invasive assessment of coronary artery bypass graft patency using 16-slice computed tomography angiography
Authors: Houslay Emma S , Lawton Tristan , Sengupta Anshuman , Uren Neal G , McKillop Graham , Newby David E
Published: June 2007

Background

Invasive coronary angiography is the gold standard means of imaging bypass vessels and carries a small but potentially serious risk of local vascular complications, including myocardial infarction, stroke and death. We evaluated computed tomography as a non-invasive means of assessing graft patency.

Methods

Fifty patients with previous coronary artery bypass surgery who were listed for diagnostic coronary angiography underwent contrast enhanced computed tomography angiography using a 16-slice computed tomography scanner. Images were retrospectively gated to the electrocardiogram and two dimensional axial, multiplanar and three dimensional reconstructions acquired. Sensitivity, specificity, positive and negative predictive value, accuracy and level of agreement for detection of graft patency by multidetector computed tomography.

Results

A total of 116 grafts were suitable for analysis. The specificity of CT for the detection of graft patency was 100%, with a sensitivity of 92.8%, positive predictive value 100%, negative predictive value 85.8% and an accuracy of 94.8%. The kappa value of agreement between the two means of measuring graft patency was 0.9. Mean radiation dose was 9.0 ± 7.2 mSv for coronary angiography and 18.5 ± 4 mSv for computed tomography. Pooled analysis of eight studies, incorporating 932 grafts, confirmed a 97% accuracy for the detection of graft patency by multidetector computed tomography.

Conclusion

Computed tomography is an accurate, rapid and non-invasive method of assessing coronary artery bypass graft patency. However, this was achieved at the expense of an increase in radiation dose.
Genetic flux over time in the Salmonella lineage
Authors: Vernikos Georgios S , Thomson Nicholas R , Parkhill Julian
Published: June 2007

Background

DNA sequences that are shared between closely related organisms while being absent from their common ancestor and from sister lineages of that ancestor are likely to have been acquired by horizontal gene transfer. Over time, the composition of those sequences tends to become more similar to the compositional signature of their host (amelioration).

Results

From a whole-genome comparative analysis of eleven Salmonella, three Escherichia coli and one Shigella strain, we inferred the relative time of insertion of putative horizontally acquired (PHA) genes in three Salmonella strains on different branches of the S. enterica phylogenetic tree. Compositional analysis suggests that most of the PHA genes are still undergoing an amelioration process and shows a clear correlation between time of insertion and the level of amelioration.

Conclusion

The results show that older insertions include almost all functional classes. However, very recent horizontal transfer events in the Salmonella lineage involve primarily prophage elements that are shared only between very recently diverged lineages; despite this, the prophage sequence composition is close to that of the host, indicating that host adaptation, rather than amelioration, is likely to be the source of the compositional similarity. Almost half of the PHA genes were acquired at the base of the Salmonella lineage, whereas nearly three-quarters are shared between most S. enterica subspecies. The numerical distribution of PHA genes in the Salmonella tree topology correlates well with the divergence of the major Salmonella species, highlighting the major impact of horizontal transfer on the evolution of the salmonellae.
Large-scale analysis of transcriptional cis-regulatory modules reveals both common features and distinct subclasses
Authors: Li Long , Zhu Qianqian , He Xin , Sinha Saurabh , Halfon Marc S
Published: June 2007

Background

Transcriptional cis-regulatory modules (for example, enhancers) play a critical role in regulating gene expression. While many individual regulatory elements have been characterized, they have never been analyzed as a class.

Results

We have performed the first such large-scale study of cis-regulatory modules in order to determine whether they have common properties that might aid in their identification and contribute to our understanding of the mechanisms by which they function. A total of 280 individual, experimentally verified cis-regulatory modules from Drosophila were analyzed for a range of sequence-level and functional properties. We report here that regulatory modules do indeed share common properties, among them an elevated GC content, an increased level of interspecific sequence conservation, and a tendency to be transcribed into RNA. However, we find that dense clustering of transcription factor binding sites, especially homotypic clustering, which is commonly believed to be a general characteristic of regulatory modules, is rather a feature that belongs chiefly to a specific subclass. This has important implications for current computational approaches, many of which are biased toward this subset. We explore two new strategies to assess binding site clustering and gauge their performances with respect to their ability to detect all 280 modules and various functionally coherent subsets.

Conclusion

Our findings demonstrate that cis-regulatory modules share common features that help to define them as a class and that may lead to new insights into mechanisms of gene regulation. However, these properties alone may not be sufficient to reliably distinguish regulatory from non-regulatory sequences. We also demonstrate that there are distinct subclasses of cis-regulatory modules that are more amenable to in silico detection than others and that these differences must be taken into account when attempting genome-wide regulatory element discovery.
Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains
Authors: Rohmer Laurence , Fong Christine , Abmayr Simone , Wasnick Michael , Larson Freeman Theodore J , Radey Matthew , Guina Tina , Svensson Kerstin , Hayden Hillary S , Jacobs Michael , Gallagher Larry A , Manoil Colin , Ernst Robert K , Drees Becky , Buckley Danielle , Haugen Eric , Bovee Donald , Zhou Yang , Chang Jean , Levy Ruth , Lim Regina , Gillett Will , Guenthener Don , Kang Allison , Shaffer Scott A , Taylor Greg , Chen Jinzhi , Gallis Byron , D'Argenio David A , Forsman Mats , Olson Maynard V , Goodlett David R , Kaul Rajinder , Miller Samuel I , Brittnacher Mitchell J
Published: June 2007

Background

Francisella tularensis subspecies tularensis and holarctica are pathogenic to humans, whereas the two other subspecies, novicida and mediasiatica, rarely cause disease. To uncover the factors that allow subspecies tularensis and holarctica to be pathogenic to humans, we compared their genome sequences with the genome sequence of Francisella tularensis subspecies novicida U112, which is nonpathogenic to humans.

Results

Comparison of the genomes of human pathogenic Francisella strains with the genome of U112 identifies genes specific to the human pathogenic strains and reveals pseudogenes that previously were unidentified. In addition, this analysis provides a coarse chronology of the evolutionary events that took place during the emergence of the human pathogenic strains. Genomic rearrangements at the level of insertion sequences (IS elements), point mutations, and small indels took place in the human pathogenic strains during and after differentiation from the nonpathogenic strain, resulting in gene inactivation.

Conclusion

The chronology of events suggests a substantial role for genetic drift in the formation of pseudogenes in Francisella genomes. Mutations that occurred early in the evolution, however, might have been fixed in the population either because of evolutionary bottlenecks or because they were pathoadaptive (beneficial in the context of infection). Because the structure of Francisella genomes is similar to that of the genomes of other emerging or highly pathogenic bacteria, this evolutionary scenario may be shared by pathogens from other species.
Characterization and modeling of the Haemophilus influenzae core and supragenomes based on the complete genomic sequences of Rd and 12 clinical nontypeable strains
Authors: Hogg Justin S , Hu Fen Z , Janto Benjamin , Boissy Robert , Hayes Jay , Keefe Randy , Post J Christopher , Ehrlich Garth D
Published: June 2007

Background

The distributed genome hypothesis (DGH) posits that chronic bacterial pathogens utilize polyclonal infection and reassortment of genic characters to ensure persistence in the face of adaptive host defenses. Studies based on random sequencing of multiple strain libraries suggested that free-living bacterial species possess a supragenome that is much larger than the genome of any single bacterium.

Results

We derived high depth genomic coverage of nine nontypeable Haemophilus influenzae (NTHi) clinical isolates, bringing to 13 the number of sequenced NTHi genomes. Clustering identified 2,786 genes, of which 1,461 were common to all strains, with each of the remaining 1,328 found in a subset of strains; the number of clusters ranged from 1,686 to 1,878 per strain. Genic differences of between 96 and 585 were identified per strain pair. Comparisons of each of the NTHi strains with the Rd strain revealed between 107 and 158 insertions and 100 and 213 deletions per genome. The mean insertion and deletion sizes were 1,356 and 1,020 base-pairs, respectively, with mean maximum insertions and deletions of 26,977 and 37,299 base-pairs. This relatively large number of small rearrangements among strains is in keeping with what is known about the transformation mechanisms in this naturally competent pathogen.

Conclusion

A finite supragenome model was developed to explain the distribution of genes among strains. The model predicts that the NTHi supragenome contains between 4,425 and 6,052 genes with most uncertainty regarding the number of rare genes, those that have a frequency of <0.1 among strains; collectively, these results support the DGH.
Mammography Surveillance and Mortality in Older Breast Cancer Survivors
Authors: Lash Timothy L. , Fox Matthew P. , Buist Diana S.M. , Wei Feifei , Field Terry S. , Frost Floyd J. , Geiger Ann M. , Quinn Virginia P. , Yood Marianne Ulcickas , Silliman Rebecca A.
Published: June 2007

Purpose

There are more than 2,000,000 breast cancer survivors in the United States today. While surveillance for asymptomatic recurrence and second primary is included in consensus recommendations, the effectiveness of this surveillance has not been well characterized. Our purpose is to estimate the effectiveness of surveillance mammography in a cohort of breast cancer survivors with complete ascertainment of surveillance mammograms and negligible losses to follow-up.

Patients and Methods

We enrolled 1,846 stage I and II breast cancer patients who were at least 65 years old at six integrated health care delivery systems. We used medical record review and existing databases to ascertain patient, tumor, and therapy characteristics, as well as receipt of surveillance mammograms. We linked personal identifiers to the National Death Index to ascertain date and cause of death. We matched four controls to each breast cancer decedent to estimate the association between receipt of surveillance mammogram and breast cancer mortality.

Results

One hundred seventy-eight women died of breast cancer during 5 years of follow-up. Each additional surveillance mammogram was associated with a 0.69-fold decrease in the odds of breast cancer mortality (95% CI, 0.52 to 0.92). The protective association was strongest among women with stage I disease, those who received mastectomy, and those in the oldest age group.

Conclusion

Given existing recommendations for post-therapy surveillance, trials to compare surveillance with no surveillance are unlikely. This large observational study provides support for the recommendations, suggesting that receipt of surveillance mammograms reduces the rate of breast cancer mortality in older patients diagnosed with early-stage disease.
The retromer component sorting nexin-1 is required for efficient retrograde transport of Shiga toxin from early endosome to the trans Golgi network
Authors: Bujny Miriam V. , Popoff Vincent , Johannes Ludger , Cullen Peter J.
Published: June 2007

The mammalian retromer complex is a multi-protein complex that regulates retrograde transport of the cation-independent mannose 6-phosphate receptor (CI-MPR) from early endosomes to the trans Golgi network (TGN). It consists of two subcomplexes: a membrane-bound coat comprising sorting nexin-1 (SNX1) and possibly sorting nexin-2 (SNX2), and a cargo-selective subcomplex, composed of VPS26, VPS29 and VPS35. In addition to the retromer, a variety of other protein complexes has been suggested to regulate endosome-to-TGN transport of not only the CI-MPR but a wide range of other cargo proteins. Here, we have examined the role of SNX1 and SNX2 in endosomal sorting of Shiga and cholera toxins, two toxins that undergo endosome-to-TGN transport en route to their cellular targets located within the cytosol. By using small interfering RNA (siRNA)-mediated silencing combined with single-cell fluorescent-toxin-uptake assays and well-established biochemical assays to analyze toxin delivery to the TGN, we have established that suppression of SNX1 leads to a significant reduction in the efficiency of endosome-to-TGN transport of the Shiga toxin B-subunit. Furthermore, we show that for the B subunit of cholera toxin, retrograde endosome-to-TGN transport is less reliant upon SNX1. Overall, our data establish a role for SNX1 in the endosome-to-TGN transport of Shiga toxin and are indicative for a fundamental difference between endosomal sorting of Shiga and cholera toxins into endosome-to-TGN retrograde transport pathways.
Improved native affinity purification of RNA
Authors: Batey Robert T. , Kieft Jeffrey S.
Published: June 2007

RNA biochemical or structural studies often require an RNA sample that is chemically pure, and most protocols for its in vitro production use denaturing polyacrylamide gel electrophoresis to achieve this. Unfortunately, many RNAs do not quantitatively refold into an active conformation after denaturation, creating significant problems for downstream characterization or use. In addition, this traditional purification method is not amenable to studies demanding high-throughput RNA production. Recently, we presented the first general method for producing almost any RNA sequence that employs an affinity tag that is removed during the purification process. Because technical difficulties prevented application of this method to many RNAs, we have developed an improved version that utilizes a different activatable ribozyme and affinity tag that are considerably more robust, rapid, and broadly applicable.
The US Army Uses Decision Analysis in Designing Its US Installation Regions
Authors: Trainor Timothy E. , Parnell Gregory S. , Kwinn Brigitte , Brence John , Tollefson Eric , Downes Pat
Published: June 2007

Senior leaders responsible for managing US Army installations asked the United States Military Academy to analyze the regional organization of the US Army’s Installation Management Agency (IMA) and recommend alternatives. They wanted an analysis of IMA’s use of four geographical regions to manage installations in the continental United States. We interviewed stakeholders to identify the functions of the IMA regional organization. We used decision analysis to define the potential value added of various regional alternatives by measuring how well each alternative would perform the functions. The measures captured the effectiveness and efficiency of the regional organization for each function. We then developed and evaluated several regional alternatives (one region, two regions, three regions, four regions, five regions, and eight regions). Using decision analysis, we showed that four was a reasonable number of regions to manage installations effectively. We demonstrated that decreasing the number of regions below four would significantly reduce the value regions added to installation management and increasing the number would provide little additional benefit.
Indiana University’s Kelley School of Business Uses Integer Programming to Form Equitable, Cohesive Student Teams
Authors: Cutshall Rex , Gavirneni Srinagesh , Schultz Kenneth
Published: June 2007

We used integer programming to form student teams for case studies in the integrated core courses at Indiana University. The previous assignment method achieved academic balance but was time consuming and limited. We developed and implemented an integer-programming-based computerized method for forming teams. It achieves equity in team members’ academic performance, functional diversity, and demographic balance. Students perceived the system as fairer than the previous method, and it forms teams of students that work better together. Students complain less about other team members, and the students and the instructors report improvement in their experience. Indiana University’s Kelley School of Business has adopted the integer-programming method for forming the teams for its I-core group of four courses.
The Ombudsman: Value of Expertise for Forecasting Decisions in Conflicts
Authors: Green Kesten C. , Armstrong J. Scott
Published: June 2007

In important conflicts such as wars and labor-management disputes, people typically rely on the judgment of experts to predict the decisions that will be made. We compared the accuracy of 106 forecasts by experts and 169 forecasts by novices about eight real conflicts. The forecasts of experts who used their unaided judgment were little better than those of novices. Moreover, neither group’s forecasts were much more accurate than simply guessing. The forecasts of experienced experts were no more accurate than the forecasts of those with less experience. The experts were nevertheless confident in the accuracy of their forecasts. Speculating that consideration of the relative frequency of decisions across similar conflicts might improve accuracy, we obtained 89 sets of frequencies from novices instructed to assume there were 100 similar situations. Forecasts based on the frequencies were no more accurate than 96 forecasts from novices asked to pick the single most likely decision. We conclude that expert judgment should not be used for predicting decisions that people will make in conflicts. When decision makers ask experts for their opinions, they are likely to overlook other, more useful, approaches.
Dell Uses a New Production-Scheduling Algorithm to Accommodate Increased Product Variety
Authors: Loveland Jennifer L. , Monkman Susan K. , Morrice Douglas J.
Published: June 2007

Early in 2003, with continually increasing product variety and production volumes, Dell, Inc. had reached the designed capacity limits of one of its main production facilities, the Morton L. Topfer Manufacturing Center (TMC). In 2004, TMC was facing a doubling of the number of product families it produced, with an anticipated degradation in production rates of nearly 20 percent. To help assuage this problem, we developed a new production-scheduling algorithm, which contains both optimization and heuristic components. The algorithm schedules product families on parallel, identical kitting lines to minimize the number of setups required and to reduce downtime and slow time during setups. Because of our work, Dell was able to accommodate the twofold increase in product variety, as well as an effective production-volume increase of over 35 percent. Furthermore, Dell realized a conservative cost avoidance of more than {$}1 million annually, primarily because it saved overtime costs that it would have required, in the absence of our solution, to handle the increases in production volume and product variety. This solution has been in operation at TMC since June 2004.
Morehead City, NC, Uses an ARIMA Study to End a State Moratorium on New Construction
Authors: Dellana Scott , West David
Published: June 2007

Morehead City, North Carolina, faced a moratorium on new construction because of problems with its sewage system. We developed an autoregressive integrated moving average (ARIMA) transfer function-intervention model to help town officials explain the sources of variation in the volume of sewage-treatment-plant discharge to the state officials who had imposed the moratorium on extending the sewage system lines. The results convinced the state officials that the problems were temporary, not systemic, and that the town’s efforts to rehabilitate the system were improving its operation. Consequently, the state officials cut the moratorium by at least a year, allowing development projects worth $50 million to proceed.
Rechnergestützte halbautomatische Modellierung biotechnologischer Prozesse (Semiautomatic Modeling of Biotechnical Processes)
Authors: Leifheit Jana , Heine Thomas , Kawohl Michael , King Rudibert
Published: June 2007

In diesem Beitrag wird ein Software-Werkzeug vorgestellt, das es ermöglicht, mathematische Modelle für biologische Reaktionssysteme weitgehend automatisch und in effizienter Weise zu erstellen oder zu verifizieren. Das Werkzeug basiert auf einer Kombination von statistischen, regelbasierten und qualitativen Methoden, mit denen wesentliche Informationen bezüglich möglicher Modellstrukturen gewonnen und postulierte Modellansätze systematisch überprüft werden können. Automatisierte quantitative Verfahren werden dann nur auf eine kleine Untermenge qualitativ korrekter Modelle angewandt, um letztendlich ein Modell vorzuschlagen.
Automatisierungstechnik für die künstliche Beatmung – eine Standortbestimmung (Automatic Control of Mechanical Ventilation – a Position-fixing)
Authors: Leonhardt Steffen , Mersmann Stefan
Published: June 2007

Dieser Übersichtsbeitrag beschreibt heutige und zukünftige Regelungs- und Automatisierungsaufgaben im Umfeld der künstlichen Beatmung. Anhand der Frage nach der Wechselwirkung mit dem Patienten wird der Versuch einer Eingruppierung in Kategorien unternommen. Alle Kategorien werden anschließend mit Beispielen unterlegt.
Study of Np speciation in citrate medium
Authors: Bonin L. , Den Auwer Christophe , Ansoborlo Eric , Cote Gérard , Moisy Philippe
Published: June 2007

In the framework of the French Environmental Nuclear Toxicology program, additional experiments related to the decorporation of actinides are planned. Decorporation is the removal or release from target organs (bones, liver, kidney …), tissues or cells of radioactive material previously incorporated in them, using chelating agents or other administrated pharmaceutical agents. The contradictory data on the neptunium complexation behaviour within blood and its transfer to target organs, as well as the inefficiency of therapeutic treatments, led us to study the complexation of this element with biological constituents. Within this purpose, the in vitro behaviour of Np(IV) and Np(V) in simple media simulating biological fluids was studied.

This study was more specifically focused on the behaviour of neptunium with citrate ion, which is an essential component in a number of metalloenzyme active sites. In order to determine the speciation of this system, spectrophotometry was more particularly used. Concerning the complexation phenomenon, the existence of several complexes of Np(V) with various acido-basic forms of the citrate anion was observed; regarding Np(IV), complexes with Cit3- have been observed. From the quantitative study of these equilibria, the values of the absolute constants for the complexation of Np(IV) and Np(V) with citrate were determined.

Concerning the stability of neptunium towards oxydo-reduction, it was confirmed that Np(VI) was very quickly reduced to Np(V) by the citrate anions, whereas Np(IV) was stable. In the case of Np(V), it was observed that, depending on the pH and the citrate concentration, Np(V) was unstable and was reduced to Np(IV). The E–pH diagrams, constructed using the stability constants determined in this study, showed that this instability was due to the Np(V) disproportionation.
Detection and Significance of Serum Protein Marker of Hirschsprung Disease
Authors: Wang Jia-xiang , Qin Pan , Liu Qiu-liang , Yang He-ying , Fan Ying-zhong , Yu Jie-kai , Zheng Shu
Published: June 2007

OBJECTIVE. The objective of this study was to identify a specific fingerprint chromatogram model of serum proteins for early screening and diagnosis of Hirschsprung disease.

METHODS. To detect the protein mass spectrograms of 78 serum specimens (42 specimens of Hirschsprung disease, 16 specimens of adhesive ileus including appendicitis and Meckel diverticulum after operation and inflammatory bowel disease, and 20 specimens of normal control subjects), we used surface-enhanced laser desorption/ionization time of flight mass spectrometry technology, combined with bioinformatics methods (support vector machine) to develop and compare protein mass spectrograms from serum samples.

RESULTS. We identified 3 protein markers, the mass-to-charge ratio of which is positioned at 3221.7, 5639.2, and 6884.2 from the fingerprint chromatogram model of serum protein for early screening and diagnosis of Hirschsprung disease. The markers had 100% sensitivity and specificity.

CONCLUSION. The fingerprint chromatogram model of serum protein using surface-enhanced laser desorption/ionization time of flight mass spectrometry technology combining support vector machine is a new method of early screening and diagnosis of Hirschsprung disease that is worthy of additional research and application.
Makro- és mikroelem-tartalom összehasonlítása almaültetvények talajában
Authors: Nagy Péter Tamás
Published: June 2007

In a
three-year study carried out at the Debrecen-Pallagi nursery of the University
of Debrecen, the nutrient contents, humus content and pH of the soil were
determined in integrated and organic apple orchards established on brown forest
soil with thin interstratified layers of colloid and sesquioxide accumulation.
The organic orchard was only given organic manure (50 t/ha) in spring 2000 and
2002, while the integrated orchard was treated with 250 kg/ha complex NPK
fertilizer (16.5-16.5-16.5) every year between 1997 and 2003 after the leaves
had fallen. An additional 50 kg/ha N active agent as NH
4
NO
3

was applied every year, while 4 t/ha lime fertilizer (carbonation mud) was
provided in autumn 2002 and 25 t/ha organic manure in November 2003. In 2004 no
fertilizer was given to either orchard. The available forms of N (NO
3-
,
NH
4+
, organic N and total N) and P (ortho-, organic and
total-PO
43-
) were determined after extraction with 0.01
M

CaCl
2
, while the Ca, Mg and microelement (Mn, Cu, Zn) content of the
soil was extracted with NH
4
-acetate +EDTA (Lakanen-Erviö
extractant). Potassium was measured in both extractants. The results showed
that the inorganic, organic and total soluble
nitrogen
in the soil were
significantly higher (P = 0.05) in the integrated orchard than in the organic
one. It was found that the quantity and ratio of the organic N fraction was
comparable with that of the inorganic N forms. The ortho-
phosphate
and
total P fractions were significantly higher (P = 0.05) in the integrated apple
orchard than in the organic orchard, while there was no significant difference
in the organic P quantity. The
potassium
data showed that both the
integrated and organic orchards contained a satisfactory amount of adsorbed K
in spite of the poor colloid content and high soil acidity. The Ca, Mg, Co and
Zn contents of the integrated soils were significantly higher (P = 0.05) than
in the organic orchard. For Mn, however, no substantial difference was found
between the integrated and organic orchards. With the exception of Mn, the
nutrient concentrations reflected the differences in the nutrient management of
the integrated and organic apple orchards.
Króm(III)-pikolinát vizsgálata a talaj-növény rendszerben
Authors: Szegvári Ildikó , Simon László , Prokisch József
Published: June 2007

A Cr(III)-pikolinát hatását vizsgáltuk a
takarmányretek
(Raphanus sativus
L. convar.
oleiformis
Pers., cv.
Leveles olajretek) krómfelvételére tenyészedényes kísérletekben. Az első
kísérletben öt (0-0,1-1-10-100 mg·kg
-1
koncentráció), a második
kísérletben két kezelést (1´, ill. 4´10 mg·kg
-1
koncentráció) állítottunk be három
ismétlésben, összesen 21 edényt használva a kísérletekhez. A humuszos
homoktalajban [pH(KCl): 7,48; leiszapolható rész: 13,2 m/m%; humusz: 0,97 m/
m%; szénsavas mész: 2,2 m/m%; T-érték: 6,2 cmol
c
·kg
-1
;
„összes” króm: 10,6  mg·kg
-1
]
nevelt növények kis mennyiségű krómot akkumuláltak gyökerükben (5,98 mg·kg
-1
)
és hajtásukban (1,38 mg·kg
-1
). A talajba közvetlenül kijuttatott
Cr(III)-pikolinát hatására jelentősen megnőtt a takarmányretek hajtásának,
illetve gyökerének krómtartalma. A kisdózisú kezelés hatására (10 mg·kg
-1
)
a gyökérben tízszer, a hajtásban kétszer több króm jelent meg; a nagydózisú
kezelés (100  mg·kg
-1
) egy
nagyságrenddel nagyobb mértékű növekedést mutatott, a gyökérben százötvenszer,
a hajtásban ötvenszer több krómot mértünk. A nagy dózisban (100 mg·kg
-1
)
és a többször kis koncentrációban (4×10 mg·kg
-1
) kijuttatott
Cr(III)-pikolinát közel azonos mértékben növelte meg a króm transzlokációját a
takarmányretek növényben, mindkét kezelésnél a hajtás krómtartalma a teljes
növény krómtartalmához viszonyítva azonos értékűnek adódott (TI = 7). A
többször kijuttatott Cr(III)-pikolinát hatására az egyes növényi szervek
krómtartalma a többszörösére növekedett; a gyökérben háromszor, a hajtásban
hatszor nagyobb krómkoncentráció jelent meg az azonos koncentrációjú, egyszeri
kezeléshez képest. A Cr(III)-pikolinát jelentős mértékben megnövelte a króm
felvételét a talaj-növény rendszerben. Ennek a jelenségnek gyakorlati
jelentősége lehet a krómmal szennyezett talajok növényekkel történő tisztítása
(fitoremediációja), illetve a krómmal dúsított növények előállítása során.
Különböző módon előkezelt települési szennyvíziszapok hatása a talaj mikroorganizmusaira és enzimaktivitására
Authors: Uri Zsuzsanna , Lukácsné Veres Edina , Kátai János , Simon László
Published: June 2007

A nyíregyházi
búzaszalmával komposztált szennyvíziszap, a debreceni anaerob módon rothasztott
szennyvíziszap és a miskolci riolittufával és karbidmésszel érlelt, granulált
szennyvíziszap talajmikrobiológiai hatásait tanulmányoztuk tenyészedé-nyes
kísérletben. Kezeletlen barna erdőtalajon (kontroll 0%), valamint a
szennyvíziszapokat kezelésenként 10, illetve 15%-ban tartalmazó
talajkultúrákban takarmányborsó jelzőnövényeket neveltünk. Megállapítottuk,
hogy a talaj szennyvíziszapokkal való kezelése és a talaj-mikroorganizmusok
száma és tevékenysége között szoros összefüggés van. Mindhárom iszap esetében
valamennyi mintavételi időpontban a kontrollhoz képest megemelkedtek, vagy
szignifikánsan nem csökkentek az összes baktériumszám és a mikroszkopikus
gombaszám értékei. Az iszapok fokozták az ureáz, a dehidrogenáz és a celluláz
enzim aktivitását, míg a foszfatázaktivitás lényeges változást nem mutatott.
Ezeket a kedvező hatásokat feltételezésünk szerint a szennyvíziszapokkal
bekerült, a mikrobák szaporodását és enzimtevékenységét stimuláló anyagoknak
lehet tulajdonítani. A kísérletben alkalmazott különbözőképpen előkezelt
települési szennyvízisza-pok mikrobaszámra és enzimaktivitásra gyakorolt
hatását összehasonlítva, mindhárom esetben egyértelműen pozitív, de egymástól
kissé eltérő eredményeket kaptunk. A vizsgált iszapok közül a debreceni
rothasztott és víztelenített iszap hatása kifejezetten kedvező volt. A
nyíregyházi rothasztás után komposztált iszap, valamint a miskolci granulált,
illetve ásványi anyagokkal kevert és érlelt iszap jótékony hatása kisebb
mértékű volt és közöttük lényeges különbséget nem találtunk. Az anaerob
rothasztás, mint iszapstabilizációs eljárás hatásos előkezelésnek bizonyult, de
mind-három iszapkezelés hozzájárulhat az eredményesebb végső elhelyezéshez. A
vizsgált települési szennyvíziszapok szakszerű mezőgazdasági alkalmazásuk
esetén pozitív hatást gyakorolhatnak a talajbiológiai életre, amely lényeges a
talaj anyagforgalmi dinamikájának javításában, a talaj termékenységének
fokozásában.