bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection and analysis of alternative splicing in Yarrowia lipolytica reveal structural constraints facilitating nonsense-mediated decay of intron-retaining transcripts
Authors: Mekouar Meryem , Blanc-Lenfle Isabelle , Ozanne Christophe , Da Silva Corinne , Cruaud Corinne , Wincker Patrick , Gaillardin Claude , Neuvéglise Cécile 
Published: June 2010

Abstract
Background
Hemiascomycetous yeasts have intron-poor genomes with very few cases of alternative splicing. Most of the reported examples result from intron retention in Saccharomyces cerevisiae and some have been shown to be functionally significant. Here we used transcriptome-wide approaches to evaluate the mechanisms underlying the generation of alternative transcripts in Yarrowia lipolytica, a yeast highly divergent from S. cerevisiae.

Results
Experimental investigation of Y. lipolytica gene models identified several cases of alternative splicing, mostly generated by intron retention, principally affecting the first intron of the gene. The retention of introns almost invariably creates a premature termination codon, as a direct consequence of the structure of intron boundaries. An analysis of Y. lipolytica introns revealed that introns of multiples of three nucleotides in length, particularly those without stop codons, were underrepresented. In other organisms, premature termination codon-containing transcripts are targeted for degradation by the nonsense-mediated mRNA decay (NMD) machinery. In Y. lipolytica, homologs of S. cerevisiaeUPF1 and UPF2 genes were identified, but not UPF3. The inactivation of Y. lipolyticaUPF1 and UPF2 resulted in the accumulation of unspliced transcripts of a test set of genes.

Conclusions
Y. lipolytica is the hemiascomycete with the most intron-rich genome sequenced to date, and it has several unusual genes with large introns or alternative transcription start sites, or introns in the 5' UTR. Our results suggest Y. lipolytica intron structure is subject to significant constraints, leading to the under-representation of stop-free introns. Consequently, intron-containing transcripts are degraded by a functional NMD pathway.
The transcriptional network activated by Cln3 cyclin at the G1-to-S transition of the yeast cell cycle
Authors: Ferrezuelo Francisco , Colomina Neus , Futcher Bruce , Aldea Martí 
Published: June 2010

Abstract
Background
The G1-to-S transition of the cell cycle in the yeast Saccharomyces cerevisiae involves an extensive transcriptional program driven by transcription factors SBF (Swi4-Swi6) and MBF (Mbp1-Swi6). Activation of these factors ultimately depends on the G1 cyclin Cln3.

Results
To determine the transcriptional targets of Cln3 and their dependence on SBF or MBF, we first have used DNA microarrays to interrogate gene expression upon Cln3 overexpression in synchronized cultures of strains lacking components of SBF and/or MBF. Secondly, we have integrated this expression dataset together with other heterogeneous data sources into a single probabilistic model based on Bayesian statistics. Our analysis has produced more than 200 transcription factor-target assignments, validated by ChIP assays and by functional enrichment. Our predictions show higher internal coherence and predictive power than previous classifications. Our results support a model whereby SBF and MBF may be differentially activated by Cln3.

Conclusions
Integration of heterogeneous genome-wide datasets is key to building accurate transcriptional networks. By such integration, we provide here a reliable transcriptional network at the G1-to-S transition in the budding yeast cell cycle. Our results suggest that to improve the reliability of predictions we need to feed our models with more informative experimental data.
Molecular evolution of genes in avian genomes
Authors: Nam Kiwoong , Mugal Carina , Nabholz Benoit , Schielzeth Holger , Wolf Jochen BW , Backström Niclas , Künstner Axel , Balakrishnan Christopher N , Heger Andreas , Ponting Chris P , Clayton David F , Ellegren Hans 
Published: June 2010

Abstract
Background
Obtaining a draft genome sequence of the zebra finch (Taeniopygia guttata), the second bird genome to be sequenced, provides the necessary resource for whole-genome comparative analysis of gene sequence evolution in a non-mammalian vertebrate lineage. To analyze basic molecular evolutionary processes during avian evolution, and to contrast these with the situation in mammals, we aligned the protein-coding sequences of 8,384 1:1 orthologs of chicken, zebra finch, a lizard and three mammalian species.

Results
We found clear differences in the substitution rate at fourfold degenerate sites, being lowest in the ancestral bird lineage, intermediate in the chicken lineage and highest in the zebra finch lineage, possibly reflecting differences in generation time. We identified positively selected and/or rapidly evolving genes in avian lineages and found an over-representation of several functional classes, including anion transporter activity, calcium ion binding, cell adhesion and microtubule cytoskeleton.

Conclusions
Focusing specifically on genes of neurological interest and genes differentially expressed in the unique vocal control nuclei of the songbird brain, we find a number of positively selected genes, including synaptic receptors. We found no evidence that selection for beneficial alleles is more efficient in regions of high recombination; in fact, there was a weak yet significant negative correlation between ω and recombination rate, which is in the direction predicted by the Hill-Robertson effect if slightly deleterious mutations contribute to protein evolution. These findings set the stage for studies of functional genetics of avian genes.
Analytical stresses in rough contacts
Authors: Sainsot P 
Published: June 2010

The pressure distribution generated by rough surfaces contact induces high stresses just beneath the surface. These stresses are at the origin of several failure mechanisms such as wear, crack initiation, etc. Therefore, it is important to be able to predict these stresses. This article describes an analytical model to evaluate the near surface stresses below a wavy surface. The originality of this work is to combine Herztian stresses in the general case of elliptical contacts and local stresses due to the pressure fluctuations. Furthermore, in case of wavy surfaces simple analytical solutions permit the calculation of the maximum shear stress and its location. Compared to a fully numerical method, the time of calculation is negligible; moreover, the analytical expressions give one the possibility of a better understanding of the effect of roughness parameters such as the wavelength of the asperities. Using a Fourier transform the results can be applied to rough surfaces.
Life Cycle Cost-Driven Innovations for Heavy Haul Turnouts
Authors: Ossberger H , Bishop G 
Published: June 2010

Life cycle cost (LCC) considerations are of increasing importance for all organizations making long-term investments. Developments for heavy haul applications were carried out in close cooperation with users identifying the key technical requirements and the overall cost situation. The design and material specifications of the components within a turnout have to be of the highest level with regards to axle load, dynamic forces, and accelerations to meet the demands for heavy haul. Aside from the price of a product, the supply-chain, installation, and maintenance costs coupled with the total life expectancy all have a significant impact on the LCC. Key influencing factors are: (a) initial track quality, (b) delivery logistics - track closing during installation, (c) inspection intervals, (d) time to maintain in track, (e) time for replacement of rails and components, (f) life expectancy of single components. LCC optimized turnout systems are influenced by the following features: (a) minimizing forces on rails, switches, and crossings by optimizing turnout curvature and contact/transition geometries, (b) providing ideal conditions for maintenance work (e.g. through automatic tamping throughout the whole turnout without dismantling of components), (c) using low-maintenance components in order to minimize costs for inspection and maintenance and to increase availability especially in the field of switching, detecting, and locking of the turnouts. The implementation of LCC philosophy in a state-of-the-art heavy haul turnout technology will be highlighted and demonstrated with examples.
High-Risk, High-Alert Medication Management Practices in a Regional State Psychiatric Facility
Authors: McKee Jerry , Cleary Susan 
Published: June 2010

Background The Joint Commission on Accreditation of Healthcare Organizations requires that health care organizations identify high-risk, high alert medications and develop specific processes for enhancing patient safety surrounding their use. Purpose Describe the development and implementation of a clinical pharmacy service, which identifies patients initiated on lithium, clozapine, and warfarin therapy to enable real-time consultation, decrease preventable adverse medication events, and improve the medication-use process. Methods: The facility identified lithium, clozapine, and warfarin for enhanced clinical monitoring. Lithium monitoring criteria include appropriate indication and testing for pregnancy, renal function, electrolyte levels, thyroid function, and serum drug levels. Clozapine monitoring criteria include informed consent, metabolic end points, appropriate indication, and complete blood count monitoring. Warfarin monitoring includes appropriate indication, screening for drug interactions, and international normalized ratio follow-up. Pharmacy and Laboratory information system flags were used to identify at-risk patients. Results For the initial 21 months of implementation, 419 lithium patients were evaluated, with 60.1 % meeting criteria preconsultation, and 95.7% meeting criteria postconsultation. Adverse drug reaction (ADR) reports involving lithium decreased from 6% preimplementation to 3% postimplementation. A total of 76 clozapine-initiation patients were evaluated, with 75% of patients meeting all criteria preconsultation, and 96% meeting criteria postconsultation. Two percent of ADR reports involved clozapine preimplementation, with a decrease to 1% postimplementation. Fifty-six warfarin-initiation therapy patients were followed, with 94.6% meeting all post-pharmacist review criteria. Significant changes were made in the medication dispensing system to prevent warfarin-dose administration errors. Conclusion Pharmacist-facilitated, high-alert medication monitoring plays a significant role in improving the medication-use process in this regional state psychiatric facility.
Do Not Miss Important Computer Alerts: Look-Alike Vial Alert: Purchasing for Safety
Authors: Cohen Michael R. , Smetzer Judy L. 
Published: June 2010

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them in your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the USP Medication Errors Reporting Program (MERP), which is presented in cooperation with the Institute for Safe Medication Practices. If you have encountered medication errors and would like to report them, you may call USP toll-free, 24 hours a day, at 800-233-7767 (800-23-ERROR). Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported through the ISMP ( www.ismp.org ) or USP ( www.usp.org ) Web sites or communicated directly to ISMP by calling 800-FAIL-SAFE or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Granisetron: Postanesthetic Shivering
Authors: Generali Joyce , Cada Dennis J. 
Published: June 2010

Off-Label Drug Uses This Hospital Pharmacy feature is extracted from Off-Label DrugFacts, a quarterly publication available from Wolters Kluwer Health. Off-Label DrugFacts is a practitioner-oriented resource for information about specific FDA-unapproved drug uses. This new guide to the literature will enable the health care professional/clinician to quickly identify published studies on off-label uses and to determine if a specific use is rational in a patient care scenario. The most relevant data are provided in tabular form, so the reader can easily identify the scope of information available. A summary of the data—including background, study design, patient population, dosage information, therapy duration, results, safety, and therapeutic considerations—precedes each table of published studies. References direct the reader to the full literature for more comprehensive information prior to patient care decisions. Direct questions or comments regarding “Off-Label Drug Uses” to hospitalpharmacy@wolterskluwer.com .
Integrating Susceptibility Data from Two Surveillance Programs with Unique Methodological Techniques: The Antibiogram Resistance Method or Isolate-Based Resistance Monitoring (ARMOR) Study Group
Authors: Epstein Benjamin J. , Gums John G. , Turner Phillip J. , Feldgarden Michael , Hou Wei 
Published: June 2010

Background Antimicrobial resistance can be tracked by several methods. The optimal application of surveillance strategies is an integral part in curbing the resistance epidemic. Objectives The Antimicrobial Resistance Management (ARM) and Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programs are ongoing antibiotic surveillance studies with different methodologies. Our aim was to compare susceptibility data generated by each program to determine if the two methods produce similar results. Methods ARM is a Web-based, antibiogram-driven surveillance system, whereas MYSTIC tests individual bacterial isolates in accordance with Clinical Laboratory Standards Institute methods. We compared national susceptibility rates during 1999 to 2004 from ARM and MYSTIC for Escherichia coli and Klebsiella pneumoniae. Results E. coli susceptibility was greater than 90% for all agents evaluated except ciprofloxacin and levofloxacin. Susceptibility rates in ARM and MYSTIC were similar (within 5%), with the exception of levofloxacin — for which susceptibility was reported as 92.3% in ARM and 83% in MYSTIC ( P < 0.0001). Amikacin, cefepime, ceftriaxone, imipenem, and meropenem were identified by both surveillance programs as the most active agents against E. coli and K. pneumoniae. Both systems detected increasing fluoroquinolone resistance ( P < 0.0001) and relatively stable activity among other agents tested. For K. pneumoniae, all agents displayed resistance rates less than 10%. Susceptibility rates in ARM and MYSTIC were remarkably similar. The largest difference was 2.9% for piperacillin/tazobactam (92.8% in ARM vs 95.7% in MYSTIC, P < 0.0001). Regionally, nonsusceptibility to E. coli and K. pneumoniae was similar, though for some comparisons MYSTIC reported higher rates of nonsusceptibility in the Northeast, Northwest, and South Central. Conclusion Surveillance of antibiotic activity patterns can be performed confidently with either method discussed above. Attempts should be made to integrate results from different surveillance programs to optimize surveillance.
Replacing Outdated Drugs; Humira Pen and HumaPen; No FDA Guidance on Drug Concentration Expression; mcg/kg versus mcg/kg/min
Authors: Cohen Michael R. 
Published: June 2010

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them in your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the USP Medication Errors Reporting Program (MERP), which is presented in cooperation with the Institute for Safe Medication Practices. If you have encountered medication errors and would like to report them, you may call USP toll-free, 24 hours a day, at 800-233-7767 (800-23-ERROR). Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported through the ISMP ( www.ismp.org ) or USP ( www.usp.org ) Web sites or communicated directly to ISMP by calling 800-FAIL-SAFE or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Implementation of Wireless “Intelligent” Pump IV Infusion Technology in a Not-for-Profit Academic Hospital Setting
Authors: Siv-Lee Lor , Morgan Linda 
Published: June 2010

Purpose This paper describes the implementation of wireless “intelligent” pump intravenous (IV) infusion technology in a not-for-profit academic, multicampus hospital system in the United States. Methods The process of implementing a novel infusion system in a multicampus health care institution (main campus plus three satellite campuses) is described. Details are provided regarding the timelines involved, the process for the development of the drug libraries, and the initial implementation within and across campuses. Results In early 2004, with the end of the device purchase contract period nearing, a multidisciplinary committee evaluated potential IV infusion pumps for hospital use. In April 2004, the committee selected the Plum A+ infusion system with Hospira MedNet software and wireless capabilities (Hospira Inc., Lake Forest, IL). Implementation of the single-channel IV infusion system took place July through October 2005 following installation of the wireless infrastructure throughout the multicampus facility. Implementation occurred in July, one campus at a time; the three smaller satellite campuses went “live” before the main campus. Implementation of the triple-channel IV infusion system took place in March 2006 when the wireless infrastructure was completed and fully functional throughout the campuses, software was upgraded, and drug library revisions were completed and uploaded. Conclusion “Intelligent” pump technology provided a framework to standardize drug concentrations used in the intensive care units. Implementation occurred transparently without any compromise of patient care. Many lessons were learned during implementation that explained the initial suboptimal compliance with safety software use. In response, the committee developed strategies to increase software utilization rates, which resulted in improved acceptance by nursing staff and steadily improving compliance rates. Wireless technology has supported remote device management, prospective monitoring, the avoidance of medication error, and the timely education of health care professionals regarding potential medication errors.
Cancer Chemotherapy Update: Mesna, Doxorubicin, Ifosfamide, and Dacarbazine (MAID) Regimen for Sarcomas
Authors: Waddell J. Aubrey , Solimando Dominic A. 
Published: June 2010

The increasing complexity of cancer chemotherapy now requires that pharmacists be familiar with these highly toxic agents. This column will review various issues related to preparation, dispensing, and administration of cancer chemotherapy, and review various agents, both commercially available and investigational, used to treat malignant diseases. The views expressed in this article are those of the author(s) and do not reflect the official policy of the Department of Army, Department of Defense, or US Government.
Topiramate: Smoking Cessation
Authors: Generali Joyce , Cada Dennis J. 
Published: June 2010

Off-Label Drug Uses — This Hospital Pharmacy feature is extracted from Off-Label DrugFacts, a quarterly publication available from Wolters Kluwer Health. Off-Label DrugFacts is a practitioner-oriented resource for information about specific FDA-unapproved drug uses. This new guide to the literature will enable the health care professional/clinician to quickly identify published studies on off-label uses and to determine if a specific use is rational in a patient care scenario. The most relevant data are provided in tabular form, so the reader can easily identify the scope of information available. A summary of the data—including background, study design, patient population, dosage information, therapy duration, results, safety, and therapeutic considerations—precedes each table of published studies. References direct the reader to the full literature for more comprehensive information prior to patient care decisions. Direct questions or comments regarding “Off-Label Drug Uses” to hospitalpharmacy@wolterskluwer.com .
Sertraline: Hot Flashes (Men)
Authors: Generali Joyce , Cada Dennis J. 
Published: June 2010

Off-Label Drug Uses — This Hospital Pharmacy feature is extracted from Off-Label DrugFacts, a quarterly publication available from Wolters Kluwer Health. Off-Label DrugFacts is a practitioner-oriented resource for information about specific FDA-unapproved drug uses. This new guide to the literature will enable the health care professional/clinician to quickly identify published studies on off-label uses and to determine if a specific use is rational in a patient care scenario. The most relevant data are provided in tabular form, so the reader can easily identify the scope of information available. A summary of the data—including background, study design, patient population, dosage information, therapy duration, results, safety, and therapeutic considerations—precedes each table of published studies. References direct the reader to the full literature for more comprehensive information prior to patient care decisions. Direct questions or comments regarding “Off-Label Drug Uses” to hospitalpharmacy@wolterskluwer.com .
Maraviroc
Authors: Cada Dennis J. , Levien Terri , Baker Danial E. 
Published: June 2010

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to your Pharmacy and Therapeutics Committee. Subscribers also receive monthly 1-page summary monographs on the agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation (DUE) is also provided each month. With a subscription, the monographs are sent to you in print and CD-ROM forms and are available online. Monographs can be customized to meet the needs of your facility. Subscribers to the The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. If you would like information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The November 2007 monograph topics are doripenem, thrombin, topical, zoledronic acid injection in Paget Disease and Osteoporosis, dexrazoxane, and lanreotide. The DUE is on doripenem.